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Mauricio Vladimir Umana-Ramírez, Gabriel Silva-Atencio, José Pablo Nuño
European Journal of Business and Management Research, Volume 8, pp 56-64;

This research covers a micro-management presence study, taking into consideration the three main elements of this concept, where organizational culture, project management frameworks, and leadership are found; thus, a relationship between these areas is established and detailed so that a relationship between micro-management as concept and issue from enterprise management can also be identified within a project management context. This research has been made qualitative, exploratory with a transversal denomination, creating and applying an assessment instrument to know the perspective of a small population from the Technology, Information, and Communication industry in Costa Rica; thus, taking into account these results and analyzing it against the theory, so that enterprise elements within organizational culture, project management frameworks and leadership, where micro-management could accommodate can be identified, as results of this research, by placing several significant symptoms and scenarios where team's performance and motivation are affected negatively.
, Maria V. Sanchez-Vives
Published: 19 December 2016
Frontiers in Robotics and AI, Volume 3;

Virtual reality (VR) started about 50 years ago in a form we would recognize today [stereo head-mounted display (HMD), head tracking, computer graphics generated images] – although the hardware was completely different. In the 1980s and 1990s, VR emerged again based on a different generation of hardware (e.g., CRT displays rather than vector refresh, electromagnetic tracking instead of mechanical). This reached the attention of the public, and VR was hailed by many engineers, scientists, celebrities, and business people as the beginning of a new era, when VR would soon change the world for the better. Then, VR disappeared from public view and was rumored to be “dead.” In the intervening 25 years a huge amount of research has nevertheless been carried out across a vast range of applications – from medicine to business, from psychotherapy to industry, from sports to travel. Scientists, engineers, and people working in industry carried on with their research and applications using and exploring different forms of VR, not knowing that actually the topic had already passed away. The purpose of this article is to survey a range of VR applications where there is some evidence for, or at least debate about, its utility, mainly based on publications in peer-reviewed journals. Of course not every type of application has been covered, nor every scientific paper (about 186,000 papers in Google Scholar): in particular, in this review we have not covered applications in psychological or medical rehabilitation. The objective is that the reader becomes aware of what has been accomplished in VR, where the evidence is weaker or stronger, and what can be done. We start in Section 1 with an outline of what VR is and the major conceptual framework used to understand what happens when people experience it – the concept of “presence.” In Section 2, we review some areas where VR has been used in science – mostly psychology and neuroscience, the area of scientific visualization, and some remarks about its use in education and surgical training. In Section 3, we discuss how VR has been used in sports and exercise. In Section 4, we survey applications in social psychology and related areas – how VR has been used to throw light on some social phenomena, and how it can be used to tackle experimentally areas that cannot be studied experimentally in real life. We conclude with how it has been used in the preservation of and access to cultural heritage. In Section 5, we present the domain of moral behavior, including an example of how it might be used to train professionals such as medical doctors when confronting serious dilemmas with patients. In Section 6, we consider how VR has been and might be used in various aspects of travel, collaboration, and industry. In Section 7, we consider mainly the use of VR in news presentation and also discuss different types of VR. In the concluding Section 8, we briefly consider new ideas that have recently emerged – an impossible task since during the short time we have written this page even newer ideas have emerged! And, we conclude with some general considerations and speculations. Throughout and wherever possible we have stressed novel applications and approaches and how the real power of VR is not necessarily to produce a faithful reproduction of “reality” but rather that it offers the possibility to step outside of the normal bounds of reality and realize goals in a totally new and unexpected way. We hope that our article will provoke readers to think as paradigm changers, and advance VR to realize different worlds that might have a positive impact on the lives of millions of people worldwide, and maybe even help a little in saving the planet. “It’s a very interesting kind of reality. It’s absolutely as shared as the physical world. Some people say that, well, the physical world isn’t all that real. It’s a consensus world. But the thing is, however real the physical world is – which we never can really know – the virtual world is exactly as real, and achieves the same status. But at the same time it also has this infinity of possibility that you don’t have in the physical world: in the physical world, you can’t suddenly turn this building into a tulip; it’s just impossible. But in the virtual world you can …. [Virtual reality] gives us this sense of being able to be who we are without limitation; for our imagination to become objective and shared with other people.” Jaron Lanier, SIGGRAPH Panel 1989, Virtual Environments and Interactivity: Windows to the Future. Although said more than 25 years ago by the person who coined the term “virtual reality” (VR) this statement about the excitement and potentiality that was apparently just around the corner in the late 1980s really does apply today. The dream at the time was a VR that would be available cheaply on a mass scale worldwide. The expectation and hope was very high. As Timothy Leary said in the following year’s SIGGRAPH Panel, imagining a time when the cost of an HMD and body-tracking equipment would be at low-end consumer level, “… suddenly the barriers of class and linguistics and education and nationality are gone. The kid in the inner city can slip on the telepresence hardware and talk to young people in China or Russia. And have flirtations with kids in Japan. In other words, to me there is something wonderfully democratic about cyberspace. If it’s virtual you can be anyone, you can be anything this time around. We are getting close to a place where that is feasible.” Unfortunately, the feasibility was not there, or at least not realizable at that time or anywhere near it. Now though the possibility is real, and for whatever reason now is the time. During the past 25 years when VR was supposed to have “died”1 masses of research into both the development of the technology and its application in a vast array of areas has been continuing. Scott Fisher, one of the VR pioneers in a 1989 essay reported in Packer and Jordan (2002) set out a number of applications: telepresence, where VR provides an interface through which the participant operates in a distant place embodied in a robot located there; data visualization; applications in architectural visualization; medicine including surgical simulation; education and entertainment; remote collaboration. These were all applications that were being worked on at the time. In this article, we set out how VR has been used in these and in a variety of other applications, applications that have already shown results that may be of significant benefit for individuals and society. With VR available on a mass scale, the potential for these benefits to have significant impact is now all the greater. However, as Jaron Lanier also said in the 1990 panel “… there’s really a serious danger of expectations being raised too high.” This remains true today, but we can have slightly less caution since research in the intervening quarter of a century has demonstrated results that stand on a reasonably solid scientific basis. For an overview of a range of applications of VR (not all considered in this article), see the paper by one of the pioneers of VR, Frederick Brooks (1999), with an updated discussion by Slater (2014). What follows is not meant to be a survey of all possible results in all possible applications. We have selected areas that we believe are particularly important for demonstrating how VR has been and might be used to improve the lives of people, and to help overcome some societal problems, or at the very least help in scientific understanding of problems and contribute toward solutions. Readers might find that their favorite topic, research result, or paper has not been mentioned. This is because we have focused on illustrative results and developments rather than attempting to be comprehensive. Indeed, to write comprehensively about every section in this article would require something like the whole article length devoted to it. Even so without trying to be comprehensive, we have found it necessary to cite many references. We have concentrated on scientific papers in peer-reviewed journals. Immersive VR has shown an extremely impressive array of applications over the years, but what is important now, given the lesson of what happened in its first phase, is that we emphasize results that have some level of scientific support. The scope of this article is on the uses of VR; we are not presenting techniques, methods, interfaces, algorithms, or any of the technical side, except where this is relevant to explain a particular application or results. Our thesis is similar to that presented in the quote from Jaron Lanier above: VR offers us a way to simulate reality. We do not say that it is “exactly as real” as physical reality but that VR best operates in the space that is just below what might be called the “reality horizon.” If a virtual knife stabs you, you are not going to be physically injured but nevertheless might feel stress, anxiety, and even pain. If a virtual human unexpectedly kisses you, you may blush with embarrassment, and your heart start pounding, but it will be a virtual kiss only. On the other hand, as Lanier said, the real power of VR is to go beyond what is real, it is more than simulation, it is also creation, allowing us to step out of the bounds of reality and experience paradigms that are otherwise impossible. Virtual reality is “reality” that is “virtual.” This means that, in principle, anything that can happen in reality can be programed to happen but “virtually,” a point that we return to in Chapter 8, since, for example, this is not the case with touch and force feedback. Therefore, writing about the potentialities inherent in VR is a difficult task – since it encompasses what can be done in physical reality (for good or evil). But even more, since it is VR, we emphasize that we can break out of the bounds of reality and accomplish things that cannot be done in physical reality. Herein lies its real power. With VR we can, for example, simulate and improve traditional physiotherapy by making it more interesting for the patient by changing their apparent location and activity to something more interesting than just what they are actually doing. In reality, a machine might be helping someone to move their legs for physiotherapy, but with VR they can be given the illusion that rather than just moving their legs for therapy they might be playing soccer in the World Cup. This type of approach augments current practices. But, VR can go way beyond this and introduce radical paradigm shifts. In VR we are currently still at the stage similar to that of the transition between theater and movies as pointed out by Pausch et al. (1996). Movies were originally just another way to show theater. It took a while before moviemakers developed a new grammar, ways of presenting a story unique to this medium. So, the same will be true of VR. Nowadays, a computer game in VR is just a traditional computer game – but displayed in a different medium. Eventually there will be a paradigm shift, one that we cannot know at the time of writing. Putting this another way, VR is revolutionary, even though it has taken 50 years to get from the initial idea in the lab to becoming a mass consumer product. How this product might develop and change the world in which we live remains unknown. In this article, we try to set out some of what has been done with VR and to some extent what might be done. We address positive uses of VR, while recognizing from the outset that there will be, like with any technology, uses that are morally repugnant. For example, vehicles can do serious damage when used improperly, even though their designed purpose is to transport people or facilitate commercial activity. The idea of immersive VR in the form that we think of it today was foreshadowed by Ivan Sutherland in 1965 (Sutherland, 1965) and then realized with the “Sword of Damocles” HMD described in a paper published 3 years later (Sutherland, 1968).2 This was not the first ever HMD – see, for example, a collection of pictures compiled by Stephen R. Ellis of NASA Ames, which includes one dating back to 1613.3 Nor was this the first ever virtual environment system – see the multisensory Sensorama system by Morton Heilig,4 or Myron Krueger’s pioneering work on Artificial Reality (Krueger et al., 1985; Krueger, 1991), or the years of work on flight simulators (Page, 2000). However, it was the first that, although using almost totally different technology than available today, introduced (and implemented) the concepts that make up a VR system. An HMD delivers two computer-generated images, one for each eye. The 2D images are computed and rendered with appropriate perspective with respect to the position of each eye in the three-dimensionally described virtual scene. Together, the images therefore form a stereo pair. The two small displays are placed in front of the corresponding eye, with some optics that enables the user to see the images. The displays are mounted in a frame, which additionally has a mechanism to continually capture the position and orientation of the user’s head, and therefore gaze direction (assuming that the eyes are looking straight ahead). Hence, as the head of the user moves, turns, or looks up and down, this information is transmitted to the computer that recomputes the images and sends the resulting signals to the displays. From the point of view of the users, it is as if they are in an alternate life-sized environment, since wherever they look, in whichever direction, they see this surrounding computer-generated world in 3D stereo with movement and motion parallax. (The same can be done with specialized sound.) In fact, from this point on we drop the term “user” and refer to the “participant.” VR is different from other forms of human–computer interface since the human participates in the virtual world rather than uses it. In the 1980s, NASA Ames developed the VIEW system (Virtual Interface Environment Workstation) described by Fisher et al. (1987).5 This was a full VR system with all components recognizable today: head-tracked wide field-of-view relatively light weight HMD, audio, tracking of the body, tracked gloves that allowed participants to interact with virtual objects, tactile and force feedback (haptics), and where the VR could be linked to a telerobotics system (Section 6.4). Also in the 1980s a company VPL led by Jaron Lanier became a driving force of VR developments constructing the Eyephone HMD, tracked data gloves6 for interaction, whole body tracking, and reality built for two (Blanchard et al., 1990).7 They also developed a visual programming language that made it possible to build virtual environments with limited programming. It was a goal for people to be able to construct their virtual realities, while in VR, and immediately share these with multiple people. It was probably through the work of VPL that the idea of VR became widely publicized. The degree of excitement, creativity, speculation, visions of a positive future, belief in the near-term mass availability of VR cannot be overemphasized. Indeed, the ideas and realizations that were around in the late 1980s and early 1990s can be read anew today and have a new freshness – and are especially important because what was hoped for then (VR for the mass of people at low cost) is now becoming a reality. Readers are urged to read the proceedings of two panels that occurred at the SIGGRAPH conference in 1989 (Conn et al., 1989) and 1990 (Barlow et al., 1990) to get an idea of the excitement and promise of the heady days of early VR. Head-mounted display technology puts the displays close to the eyes. Another type of immersive VR system was developed by Cruz-Neira et al. (1992) referred to as a CAVE™ system (Cruz-Neira et al., 1993). Here, images are back-projected onto the walls of an approximately 3 m cubed room (front projected onto the floor by a projector mounted on the ceiling above the open topped cuboid). Typically, three walls and the floor are screens. The images are projected interlaced at, e.g., 90 frames per second, 45 showing left eye images and the others the right eye images. Lightweight shutter glasses alternately have one eye lens opaque and the other transparent, in sync with the projected images. The brain fuses the two into one overall 3D stereo scene. Through head tracking mounted on the glasses, the image is correctly perspective computed for the head position, direction, and orientation of the participant. More than one person can be in the Cave simultaneously, and wearing the stereo shutter glasses, but the perspective is only correct for the one wearing the head-tracked glasses. Hence, such Cave-like systems, like HMDs deliver a surrounding 3D world. Of course, such a system has been far more expensive than an HMD system, both in terms of the space required and the cost (high powered projectors, a multiprocessor computer system, complex software for lock-step stereo rendering across all the displays, equipment maintenance). Moreover, as the promise of HMD driven VR diminished in the 1990s through the failure to develop high quality displays at low enough cost, and with acceptable ergonomics (such as weight), Cave-like systems came to be used as an alternative. However, unlike HMDs, each Cave was typically tailor-made to order (it depended on available space apart from anything else) and never became a mass product. Caves became one of the mainstays of VR research and applications from the late 1990s and through the 2000s until recently. The applications we discuss below include both HMD and Cave systems. Conceptually, a minimal VR system places a participant into a surrounding 3D world that is delivered to a display system by a computer. At the very least, the participant’s head is tracked so that image and auditory updates depend on head-position and orientation. The computer graphics of the system delivers perspective-projected images individually to each eye, and the resulting scenario should be seen with correct parallax. Ideally, there should be a means whereby participants can effect changes in the virtual world. This may be accomplished by 3D tracked data gloves, or a handheld device such as a Wand (which is like a mouse or joystick but tracked in 3D space). Note that this says nothing about how the world is rendered. Even with the wire frame (lines only) images portrayed in Sutherland (1968), Ivan Sutherland noted that “An observer fairly quickly accommodates to the idea of being inside the displayed room and can view whatever portion of the room he wishes by turning his head ….Observers capable of stereo vision uniformly remark on the realism of the resulting images.” Consciousness of our immediate surroundings necessarily depends on the data picked up by our sensory systems – vision, sound, touch, force, taste, and smell. This is not to say that we simply reproduce the sensory inputs in our brains – far from it, perception is an active process that combines bottom-up processing of the sensory inputs with top-down processing (including prior experience, expectations, and beliefs) based on our previously existing model of the world. After a few seconds of walking into a room we think that we “know” it. In reality, eye scanning data show that we have foveated on a very small number of key points in the room, and then our eye scan paths tend to follow repeated patterns between them (Noton and Stark, 1971). The key points are determined by our prior model of what a room is. We have “seen” a small proportion of what there is to see; yet, our perceptual system has inferred a full model of the room in which we are located. In fact it has been argued that our model of the scene around us tends to drive our eye movements rather than eye movements leading to our perceptual model of the scene (Chernyak and Stark, 2001). It was argued by Stark (1995) that this is the reason why VR works, even in spite of relatively simplistic or even poor rendering of the surroundings. VR offers enough cues for our perceptual system to hypothesize “this is a room” and then based on an existing internal model infer a model of this particular room using a perceptual fill-in mechanism. Recall the quote from Sutherland above how people accommodated to and remarked on the realism of the wire frame rendered scene displayed in the “Sword of Damocles” HMD. The technical goal of VR is to replace real sense perceptions by the computer-generated ones derived from a mathematical database describing a 3D scene, animations of objects within the scene – represented as transformations over sets of mathematical objects – including changes caused by the intervention of the participant. If sensory perceptions are indeed effectively substituted then the brain has no alternative but to infer its perceptual model from its actual stream of sensory data – i.e., the VR. Hence, consciousness is transformed to consciousness of the virtual scenario rather than the real one – in spite of the participant’s sure knowledge that this is not real. Effective substitution of real sensory data is an ideal. In practice, it depends on several factors, not least of which is – which sensory systems are included? Typically, vision, and often auditory, more rarely touch, more rarely force feedback, more rarely still smell, and almost unknown taste.8 If we consider the typical VR system, it is primarily centered around vision, may have sound, and may have some element of tactile feedback. However, even vision alone is often enough for numerous applications, since anyway for many people it is perceptually dominant. So, participants in a VR typically encounter a situation where their visual system places them on say a roller coaster, but all other sense perceptions are from the surrounding physical environment. Nevertheless, they may scream and react as if they are on the roller coaster even while talking to a friend in reality standing nearby. Factors that are critical for effective sensory substitution have been known for several years (Heeter, 1992; Held and Durlach, 1992; Loomis, 1992; Sheridan, 1992, 1996; Steuer, 1992; Zeltzer, 1992; Barfield and Hendrix, 1995; Ellis, 1996; Slater and Wilbur, 1997): such as wide field-of-view vision, stereo, head tracking, low-latency from head move to display, high-resolution displays, and of course the more sensory systems that are substituted the better. However, these types of technical factors (and there are others) are for one purpose – to afford the participant to perceive using natural sensorimotor contingencies (O’Regan and Noë, 2001a,b; Noë, 2004). What this means is that in order to perceive we use our bodies in a natural way. We turn our head, move our eyes, bend down, look under, look over, look around, reach out, touch, push, pull, and doing all or some subset of these things simultaneously. Perception is a whole body action. Hence, the primary technological goal of VR is to realize perception through such natural sensorimotor contingencies to the best extent possible, and of course this continually comes up against limitations. For example, if while wearing an HMD or in a Cave we look very closely at an object, eventually we will see pixels. Or, in most existing VR systems, if we touch some arbitrary virtual object we will not feel it. By an immersive VR system we mean one that delivers the ability to perceive through natural sensorimotor contingencies. This is entirely determined by the technology. Whether you can turn around 360°, all the while seeing a very low-latency continuous update of your visual field in correspondence with your gaze direction, is completely a function of the extent to which the system can do this. We can classify systems in this way as being more or less immersive. We say that system A is more immersive than system B if A can be used to simulate the perception afforded by B but not vice versa. Hence, in this sense an HMD is “more immersive” than a Cave, since there is something that can be represented in an HMD that cannot be represented in a Cave (even a six-sided Cave): the virtual representation of the participant’s body. In a Cave when you look down toward yourself you will see your real body. In an HMD with head tracking you can see a virtual body substituting your own (if this has been programed). Moreover, the virtual body can be designed to look like the real one, or not, and certainly with body tracking can be programed to move with real body movements and so on. So, in this way an HMD-based system can (in an ideal sense) be set up to simulate a Cave, but not vice versa. Immersion describes the technical capabilities of a system, it is the physics of the system. A subjective correlate of immersion is presence. If a participant in a VR perceives by using her body in a natural way, then the simplest inference for her brain’s perceptual system to make is that what is being perceived is the participant’s actual surroundings. This gives rise to the subjective illusion that is referred to in the literature as presence – the illusion of “being there” in the environment depicted by the VR displays – in spite of the fact that you know for sure that you are not actually there. This specific feeling of “being there” has also been referred to as “place illusion” (PI) (to distinguish it from the multiple alternative meanings that have been attributed to the term “presence”) (Slater, 2009). It was coined by Marvin Minsky (1980) to describe the similar feeling that can arise when embodying a remote robotic device in a teleoperator system. Place illusion can occur in a static environment where nothing happens – just looking around a stereo-displayed scenario, for example, where nothing is changing. When there are events in the environment, events that respond to you, that correlate with your actions, and refer to you personally, then provided that the environment is sufficiently credible (i.e., meets the expectations of how objects and people are expected to behave in the type of setting depicted), this will give rise to a further and independent illusion that we refer to as “Plausibility” (Psi) that the events are really happening. Again, this is an illusion in spite of the sure knowledge that nothing real is happening. A virtual human approaches and smiles at you, and you find yourself smiling back, even though too late you may say to yourself – why did I smile back, there is no one there? The real-time update of sensory perception as a result of movement (e.g., head turning) gives rise to the sense of “being there” – the illusory sensation of being in the computer-generated environment (Sanchez-Vives and Slater, 2005). The dynamic changes following events caused by or to the participants can give rise to the illusion that the events are really happening – “plausibility” (Slater, 2009). With a technically good VR system (wide field-of-view high-resolution stereo display, with low-latency head tracking at a minimum), the “being there” aspect is essentially determined for all but a few moments during an experience (Slater and Steed, 2000). Psi is much harder to attain, often requiring specific domain knowledge (e.g., the virtual representation of a doctor’s surgery for the purposes of training had better be according to their expectations if doctors are to accept it). In this article, we use PI to refer to the illusion of being there, whereas presence refers to both PI and Psi. Following Sanchez-Vives and Slater (2005), the behavioral correlate of “presence” is that participants behave in VR as they would do in similar circumstances in reality. For a more formal treatment of PI, Psi, and presence, including experimental results, see Slater et al. (2010a).9 These issues are taken up again in Chapter 8. This fundamental aspect of VR to deliver experience that gives rise to illusory sense of place and an illusory sense of reality is what distinguishes it fundamentally from all other types of media. It is true that in response to a fire in a movie scene, the viewers’ hearts might start racing, with feelings of fear and discomfort. But, they will not run out of the cinema for fear of the fire. In VR, about 10% did run out when confronted by a virtual fire even though the fire did not look realistic (Spanlang et al., 2007). In a movie that includes a fight between two strangers in a bar, audience members will not intervene to stop the fight. In VR, they do – under the right circumstances – specifically when the victim shares some social identity with the participant (Slater et al., 2013), which itself is remarkable because obviously there is no one real there with whom to share social identity. So, VR is a powerful tool for the achievement of authentic experience – even if what is depicted might be wholly imaginary and fantastic. In a scenario with dinosaurs such as that shown in “Back to Dinosaur Island – Jurassic World with Oculus Rift,”10 of course participants know that the situation is not real. Nevertheless, they would typically have the illusion of being there and have the illusory sensation that the dinosaur’s actions are really happening. Evidence over the past 25–30 years shows that PI and Psi can occur even in quite low-level systems. This is because VR relies on the brain “filling in” detail in response to the apparent situation, so that just like in physical reality people find themselves responding with physiological and reflex actions before they consciously reason out the situation – in this case that in fact nothing real is happening. That reasoning or high-level cognitive processing occurs more slowly, after the autonomic bodily responses have already occurred. For example, put someone next to a virtual precipice and their heart will start pounding (Meehan et al., 2002), even though eventually of course they can say to themselves that it is not really there. VR effectively relies on this duality – between very rapid brain activation that causes the body to respond (by the body responding, we include autonomous responses and thoughts that are generated in response to an apparent situation) and the slower cognitive process that reasons things out, which is of course a vital mechanism for survival, and occurs normally in physical reality. Since VR evokes realistic responses in people, it is fundamentally a “reality simulator.” By this we mean that participants can be placed in a scenario that depicts potentially real events, with the likelihood that they would act and respond quite realistically. This can obviously be exploited for many applications including rehearsal for the actual events, planning, training, knowledge dissemination, and so on. However, VR is also an unreality simulator! The events that it depicts may be ones that are highly unlikely to happen or cannot happen because they violate fundamental laws of physics, such as defying the laws of gravity. In VR, the physical laws can be simulated to the limit that computational power supports, or they can be changed or violated. Similarly, social conventions can be violated. A person might one day participate in a world that has never existed, such as Pandora from James Cameron’s movie Avatar.11 But still, provided some fundamental principles are adhered to, giving rise to the illusions of being in the virtual place where real events are taking place – participants can nevertheless demonstrate realistic responses. At the simplest level your heart is likely to race equally being faced with a realistic depiction of a precipice (something that could happen) or being chased by otherworld monsters. In this way, VR dramatically extends the range of human experiences way beyond anything that is likely to be encountered in physical reality. Hence, the amazing capability of VR not just as a reality simulator but as an unreality simulator that can paradoxically give rise to realistic behavior. In this article, we will outline some of the applications that have been developed that show the positive use of VR for the potential benefit of society and individuals – how VR can be used to enhance well-being across a vast range of aspects of life. VR as a reality simulator has its uses in various forms of training, for education, for travel, some of which are discussed in the sections below. Moreover, VR as an unreality simulator can be used for many different types of entertainment – that extend from passive to active. It should also be noted that VR as an unreality simulator can also be used to solve “real” problems – as we will indicate later. In each of the sections below, we will tackle a different domain of application. We will show in each section what has been done at the time of writing and give some indication of the degree to which it has been successful (i.e., its scientific validation). Additionally, where relevant, we will discuss ideas and proposals indicating what could be done in this domain. In Franz Kafka’s Metamorphosis,12 Gregor Samsa woke up one morning lying in bed and found himself transformed into a horrible insect-like creature. The body felt like his own, but he had to learn how to move himself in new ways, and of course it had an impact on his attitudes and behaviors and those of others who saw him. Using VR, it has been shown to be possible to actually experiment with these types of body transformations, though rather more pleasant ones, and in the early days at the VPL company, there was experimentation by Jaron Lanier with embodiment in a virtual lobster body. The question of how the brain represents the body is fundamental in cognitive neuroscience. How does the brain distinguish that this object is “my” hand and part of my body, but that object, a cup, is not part of my body, or that other object is your hand and not part of me? Common sense would have us believe that our own internal body representation is stable, something that changes only slowly through time, but experiments have shown that it is quite easy to shift the illusion of body ownership to objects that are not part of the body at all, or to a radically transformed body, so that our body representation is highly malleable. A classic and very simple experiment to show this is called the rubber hand illusion (RHI) presented by Botvinick and Cohen (1998) in a one page Nature paper in 1998, which has had an enormous impact on the field (over 1800 citations – Google Scholar – at the time of writing). It has led to a vast literature that exploits these illusions to understand how the brain represents the body. Recent reviews are provided in Blanke (2012); Ehrsson (2012); and Blanke et al. (2015). In the RHI, the subject sits by a table onto which a rubber hand is placed in an anatomically plausible position, and approximately parallel to the subject’s corresponding real hand. The real hand is hidden behind a partition. The experimenter sitting opposite the subject taps and strokes the seen rubber hand and the hidden real hand synchronously in time and as far as possible at the same locations on the two hands. From the subject’s point of view, there is a rubber hand seen on the table in front, and arranged so that it could be the subject’s own hand, and this hand is seen to be tactilely stimulated. But, corresponding to the seen stimulation, there is actually felt stimulation on the real hand. The brain’s perceptual system resolves this conflict by integrating the two separate but synchronous inputs into one, resulting in the perceptual and proprioceptive illusion that the rubber hand is the subject’s hand.13,14 This feeling, just like PI or Psi, is impossible to describe – it has to be experienced. If the visual and tactile stimulation are asynchronous, then the illusion does not occur, or occurs to a much lesser extent. To elicit a behavioral measure of the illusion, the idea of “proprioceptive drift” was introduced in Botvinick and Cohen (1998). Before the stimulation, participants with eyes closed had to point to their hand under the table on which their arm was resting. After the stimulation, participants were again asked to repeat the pointing procedure. The distance between the post- and pre-measures is called the proprioceptive drift, where greater values indicate that participants pointed more toward the rubber hand after than before. Indeed, it was found that the drift was on the average positive for those in the synchronous condition and zero for those in the asynchronous. Armel and Ramachandran (2003) went on to show that subjects also respond physiologically to a threat to the rubber hand. They argued that our internal body representation is updated moment to moment based on the stimulus contingencies received. Synchronous multisensory perception leading to the hypothesis that a rubber hand might be our real hand is taken on by the brain that very quickly generates the corresponding illusion as a way to resolve the contradiction between the seen and felt synchronous stimulation. There are limitations, such as the rubber hand needing to look like a human hand, its position must be plausible, and so on, but the fundamental result that we can have strong feelings of ownership over an object that we know for certain is not part of our body is clearly demonstrated by this illusion. Lenggenhager et al. (2007)15 and Ehrsson (2007)16 went on to show how similar multisensory techniques could be used to induce out-of-body illusions. Each of these used an HMD via which subjects saw a distant body. The HMD received video signals from cameras pointing toward the body. In the case of Lenggenhager et al. (2007), the distant body was a manikin with its back to the subject. The manikin was seen to be stroked on the back, which was felt on the subject’s back through synchronous stimulation by the experimenter. Subjects then had the strange illusion of being located at or drawn toward the manikin body to their front. In the case of Ehrsson (2007), the video cameras were pointed to the back of the subject’s own seated body. So from the perspective of the subject, they saw their own body from behind themselves. The experimenter synchronously stroked the subject’s real chest (out-of-sight) and visibly made similar strokes under the cameras. From the point of view of the subjects, they saw and felt stroking toward themselves (since their viewpoint was that of the stereo cameras), but they were apparently located behind their real body. Here, the visual and tactile information cohered to generate the illusion of being behind their own body. When the space under the camera was attacked with a hammer, participants responded physiologically (since the hammer would seem to be coming toward the illusory location of their chest). When the visual and tactile stimulation was asynchronous neither the illusion nor the physiological response occurred to the same extent. Following this, a form of VR to study body ownership with respect to the whole body (full body ownership) was achieved by Petkova and Ehrsson (2008) through the use of video cameras mounted on top of a manikin that fed a stereo HMD worn by the participant, so that when participants looked down toward their real body, they would see the manikin body instead of their own. This was accompanied by visuotactile synchrony, induced by applying tactile stimulation to the real body synchronized with a corresponding visual stimulation to the manikin body. The result was subjective illusion of ownership over the manikin body, demonstrated also by a physiological response when a knife threatened that body. The illusion diminished when visuotactile asynchrony was applied. The use of VR to transform the body was first realized by Jaron Lanier, in the late 1980s. The importance of this work for cognitive neuroscience was not realized at the time, and it was never published scientifically, although see Lanier (2006) and it is referred to in Lanier (2010). Lanier used the term “homuncular flexibility” to refer to the finding that the brain can adapt to different body configurations and learn how to manipulate such an alien body – for example, manipulating end-effectors of a body representation as a lobster by learning to use muscles in the stomach, or though combinations of different muscle activations. The extreme flexibility of the body representation had been studied in the 1980s by Lackner (1988). It was found that applying vibrations of around 100 Hz to a muscle tendon on the biceps leads the forearm to move in flexion, but if the movement is resisted, then there will be an illusion of movement of the forearm in the opposite direction (extension). Now suppose that both hands are holding the waist and such muscle spindle vibrations are applied. There is an illusion that both arms are extending, but since the hands are attached to the waist this is impossible. The way that the brain resolves this is to give the illusion of an expanding waistline! By vibrating on the other side of the muscle tendons the arms can be given the illusion of flexing – which will result in a shrinking waist illusion. Ehrsson et al. (2005) used these illusions with brain imaging to capture brain activation changes associated with these radical changes in the body. Tidoni et al. (2015) used these vibratory techniques in conjunction with VR as part of a developing program for the rehabilitation of disabled patients. This followed earlier work by Leonardis et al. (2012) who used such vibrations to induce illusory movements but in conjunction with a brain–computer interface (BCI) motor-imagery paradigm, i.e., the participant imagines moving their arm, feels their arm moving through application of the vibrations technique, and then sees the corresponding virtual arm move. This was part of an Embodiment Station (discussed in Section 6.5). Regarding non-human body configurations Ehrsson (2009) and Guterstam et al. (2011) showed, for example, that using the multisensory techniques associated with the RHI, it is possible to give participants the illusion of owning additional arms. Regarding body shape, Kilteni et al. (2012)17 showed that it is possible to have an illusion of ownership over an asymmetric human body, where one arm is three times as long as another, and where the participant responds by automatically withdrawing the arm when there is a threat to the distant hand. This illusion had first been implemented and experienced at VPL in the 1980s, although not published. Steptoe et al. (2013) showed how humans could adapt to having a tail, through embodiment using a Cave-like system, but seeing the virtual body from behind. Participants learned how to use the tail in order to avoid harm to the body. More recently, Won et al. (2015a) have continued to study homuncular flexibility, showing that people can learn to control virtual bodies through mappings that are different from the usual ones. Some implications of this across a range of fields have been discussed in Won et al. (2015b). Returning to the RHI, Ijsselsteijn et al. (2006) found that an illusion of ownership can be attained over a 2D projection of an arm on a table top when the visuotactile synchronous stimulation is applied as in the RHI. Although the subjective illusion was reported, the proprioceptive drift effect did not occur. Using VR, Slater et al. (2008) showed that a virtual arm could be felt as owned by participants when seen to be stroked synchronously with the corresponding hidden real arm. This was achieved by a virtual arm being displayed on a powerwall as projecting (in stereo) out of the real shoulders of participants. A tracked wand was used to tap and stroke the participant’s hidden real hand, which was shown on the display as a virtual ball tapping the virtual hand. This was done synchronously in which case the full illusion of ownership occurred including proprioceptive drift, or asynchronously, which typically did not result in the illusion. In the full body illusion setup of Petkova and Ehrsson (2008), there was no head tracking so that participants had to be looking down in a fixed orientation toward their body, in order to see the manikin body as substituting their real body. Slater et al. (2010b) carried out the first study of full body ownership using VR where participants saw a virtual body that was spatially coincident with their own and which they saw through a wide field-of-view stereo and head-tracked Fakespace Wide5 HMD.18 Hence, when they looked down toward themselves they saw a virtual body that substituted their actual (hidden) body and from the viewpoint of the eyes of that virtual body (coincident with their own). We refer to this as first-person perspective (1PP). The experiment also included visuotactile synchrony (they felt their arm being stroked in synchrony with seeing their corresponding virtual arm stroked) or visuotactile asynchrony. There was also a condition where the virtual body was seen from a third-person perspective (3PP) (i.e., the virtual body was not spatially coincident with the real body, but to the left of the participant’s location). In this setup, it was found that 1PP was clearly the dominant factor, although visuotactile synchrony had some contribution. Remarkably, the illusion occurred in spite of the fact that all the participants were adult males but were embodied in a young female body.19 The difference between the results of Petkova and Ehrsson (2008) and Slater et al. (2010b) was taken up by Maselli and Slater (2013). The vital importance of 1PP for body ownership was also emphasized by Petkova et al. (2011) and considered further by Maselli and Slater (2014). One of the major advantages of VR in this context compared to using rubber hands or manikin bodies is that virtual limbs or the whole virtual body can be moved. Sanchez-Vives et al. (2010) exploited this to show that the illusion of ownership over a virtual arm can be induced by synchrony between real and virtual hand movements (visuomotor synchrony). Participants wearing a data glove that tracked the movements of their hand and fingers saw a virtual hand (projected in stereo 3D on a powerwall) move in synchrony or asynchrony with their real hand movements. This resulted in an illusion of ownership just as with visuotactile stimulation. The same can be done for the body as a whole. Through real-time motion capture, mapped onto the virtual body, when the person moves their real body they would see the virtual body move correspondingly. Participants can see their virtual body moving by directly looking toward themselves and in virtual mirror reflections (and shadows) (Slater et al., 2010a). Kokkinara and Slater (2014) showed in later work that when there is a 1PP view of the virtual body then visuomotor synchrony is the more powerful inducer of the body ownership illusion than visuotactile synchrony. We use the term virtual embodiment (or just embodiment) to refer to the process of replacing a person’s body by a virtual one. This requires the stereo HMD with wide field-of-view (so that the person can actually see their virtual body), with head tracking, at the minimum. Additional multisensory correlations such as visuotactile and visuomotor synchrony may be included. A technical setup to achieve this is described in Spanlang et al. (2014). Virtual embodiment may give rise under the right multisensory conditions (such as 1PP, visuotactile, and/or visuomotor synchrony) to the illusion of body ownership, which is a perceptual illusion that the virtual body feels as if it is the person’s own body (even though it may look nothing like their real body). There has been a lot of work on building virtual embodiment technology (Spanlang et al., 2013, 2014), studying the conditions that can lead to such body ownership illusions (Slater et al., 2008, 2009, 2010b; Sanchez-Vives et al., 2010; Borland et al., 2013; González-Franco et al., 2013; Llobera et al., 2013; Maselli and Slater, 2013, 2014; Pomes and Slater, 2013; Blom et al., 2014; Kokkinara and Slater, 2014) and exploring the effects of distortions away from the normal form of a person’s actual body (Slater et al., 2010b; Normand et al., 2011; Kilteni et al., 2012; Steptoe et al., 2013). There have also been studies on how illusions of body ownership might result in various changes to the real body. For example, it had previously been shown that the RHI leads to a cooling of the real hand (Moseley et al., 2008) – though see also Rohde et al. (2013) – as well as an increase in its histamine reactivity (Barnsley et al., 2011). Cooling of several points on the body has also been reported in a 3PP full body illusion (Salomon et al., 2013). There is also evidence using VR suggesting that the 1PP full body ownership illusion can result in changes in temperature sensitivity (Llobera et al., 2013). It has also been shown that when in the full body illusion the virtual hand is attacked that there is an electrical brain response (EEG) that corresponds to what would be expected to occur when a real hand is attacked (González-Franco et al., 2013). Banakou and Slater (2014) showed that embodiment in a virtual body that is perceived from 1PP and that moves synchronously with the real body can result in illusory agency over an act of speaking. The virtual body was seen directly and in a virtual mirror. Participants spent a few minutes simply moving with the virtual body moving synchronously with their movements in the experimental condition or asynchronously in another. At some moment, the virtual body unexpectedly uttered some words (45 in total) with appropriate lip sync. Those in the visuomotor synchronous condition later reported a subjective illusion of agency over the speaking – as if they had been the ones who had been speaking rather than only the virtual body. Moreover, when participants were asked to speak after this exposure, the fundamental frequency of their own voice shifted toward that of the higher frequency voice of the virtual body. Thus embodiment resulted in the preparation of a new motor plan for speaking, which was exhibited by participants in the synchronous condition changing the way that they spoke after compared to before the experiment. This did not happen for those in the asynchronous condition. Thus, VR offers a very powerful tool for the neuroscience of body representation. For a recent review of this field, see Blanke et al. (2015). It can be used to do effectively and relatively simply what is impossible by any other means – instantly produce an illusion of change to a person’s body. In the next section, we consider some of the consequences of changing representations of the self. “… one of the fundamental differences between virtual reality and other forms of user-interface is that you’re really present in it, your body is represented and you can react with it as you, … And the fact that you’re in it, and that you define yourself is really fascinating. Oftentimes, being able to change your own definition is actually part of a practical application. Like in the world we did last year, where an architect was designing a day care center and could change himself into a child and use it with a child’s body and run faster and have different proportions and all that.” Jaron Lanier (Barlow et al., 1990). This quote is another illustration that much of what is being discussed today was already thought of and even implemented in the heady days of early VR. If VR can endow someone with a different body, what consequences does this have? We have already mentioned above that ownership over a rubber hand can lead to physiological responses, and there is some evidence that points to the possibility that the experimental real arm can experience (very small) drops in temperature, and that the same can occur over different parts of the body in a virtual whole body illusion, or that in the virtual arm illusion that there may be a change in temperature sensitivity. But, are there higher-level changes to attitudes, behaviors, even cognition? Yee and Bailenson (2007) introduced a paradigm called the “Proteus Effect,” where it was argued that the digital self-representation of a person could influence their attitudes and behaviors in online and virtual environments. Essentially, the personality or type of body or the actions associated with the digital representation would influence the actual real-time behaviors of participant, both in the VR and later outside it. In their 2007 paper, they showed that being embodied in an avatar that had a face that was judged as more attractive than their actual one led participants to move closer to someone else displayed in a collaborative virtual environment than those participants whose avatar face was judged less attractive. Similarly, being embodied in taller avatars led to more aggressive behaviors in a negotiation task than being embodied in shorter avatars. These results also carried over to representations in online communities (Yee et al., 2009). Groom et al. (2009) embodied White or Black people in a Black or White virtual body, in the context of a scenario in which they were in an interview applying for a job. The embodiment was through an HMD with head tracking, with the body seen in a mirror, and lasted for just over 1 min. Using a racial Implicit Association Test (IAT) (Greenwald et al., 1998), they found after the exposure there was greater bias in favor of White for those embodied in the Black virtual body. This difference did not occur when participants simply imagined being in a White or Black body. Hershfield et al. (2011) studied the effect of embodiment in aged versions of themselves on their savings behavior. They embodied people in a virtual body that either had a representation of their own faces, or their faces aged by about 20 years. The virtual body was shown in a virtual mirror. They found some modest evidence in favor of the hypothesis that being confronted with their future selves influenced their behavior toward greater savings for the future. See also the example concerned with fostering exercise (Fox and Bailenson, 2009) in Section 3.1.2. The theoretical basis of Proteus Effect (Yee and Bailenson, 2007) is Self-Perception Theory [e.g., Bem (1972)], which suggests that people infer their attitudes by observing their own behaviors and the context in which these occur, and almost all the examples above do put people into behavioral situations. It has been also been argued that attitudinal and behavioral correlates of transformed body ownership can be explained as people behaving according to how others would expect someone with that type of body to behave (Yee and Bailenson, 2007). Essentially, this comes down to stereotyping. For example, in the case of the racial bias study of Groom et al. (2009), participants were put into precisely a situation that is known to be one where there is implicit bias against Black people compared to White. In an experiment by Kilteni et al. (2013), people were embodied either in a dark-skinned casually dressed (Jimi Hendrix-like) body or in a light-skinned virtual body. The body moved with visuomotor synchrony, but also there was synchronous visuotactile feedback through a drumming task, so that participants saw their virtual hands hit a virtual hand drum that was coincident in space with a real hand drum. Hence, when they hit the virtual drum they would also feel it.20 In this experiment, those embodied in the dark-skinned casual body expressed significantly greater body movement while drumming than those embodied in the light-skinned body that was wearing a formal suit. This result occurred, in the view of the stereotype theory, because there is greater expectation that people who look more like Jimi Hendrix would be more bodily expressive. However, self-perception theory and stereotyping cannot account for attitudinal changes that have been observed in experiments where only the body changes, and there are no particular behavioral demands within the study. These results are better explained within the multisensory perception framework based on the research that has stemmed from the RHI. Peck et al. (2013) carried out a racial bias study where participants were embodied for 12 min in either a Black body, a White one, a purple one, or no body at all. The body moved synchronously with real body movements of the participants through real-time motion capture and was seen directly by looking toward the self with the head-tracked HMD and in a mirror.21 Those in the “no body” condition saw a mirror reflection of a Black body, but which moved asynchronously to their own movements. A racial IAT was applied some days before the experience and then immediately after. It was found that average implicit racial bias significantly decreased only for those who had the Black embodiment. During the 12 min of exposure, the participant did not have any task except to move and to look toward themselves and in the mirror while doing so. The only events that occurred were that 12 virtual characters walked by, 6 of them Black and the others White. It is likely that the results are different from Groom et al. (2009) because of the much longer exposure time, the full body synchronous movement, and the fact that there was no task, so that this was only based on body ownership through multisensory perception. Given the contrary earlier result of Groom et al. (2009), it was hard to believe that just 12 min of this experience could apparently reduce implicit racial bias. However, independently it was shown by Maister et al. (2013) that the RHI over a black rubber hand also leads to a reduction of implicit racial bias in light-skinned people. For a review of this area of research see Maister et al. (2015). Recent results demonstrate that the decrease in implicit bias lasts for at least 1 week after the exposure (Banakou et al., 2016). van der Hoort et al. (2011) showed using the multisensory techniques of Petkova and Ehrsson (2008) that when average sized adults have an illusion of body ownership over smaller or larger manikin bodies that this results in changes in their perception of object sizes (in a small body objects seem to be larger, but smaller in a large body). Banakou et al. (2013) reproduced this result in immersive VR.22 They showed that the illusion of body ownership of adults over small body leads to overestimation of object sizes. However, if the form of the body represented that of a (4-year-old) child then the size overestimation was approximately double that compared to when the form of the body was an adult body but shrunk down to the same size as the child. Moreover, in the child embodiment case, there were changes in implicit attitudes about the self toward being child-like substantially beyond changes induced by the illusion of ownership of the adult-shaped body of the same size. In other words, only the form of the body (child-like compared to adult-like) has this effect. The child and racial bias studies relied on an IAT – e.g., Greenwald et al. (1998) – a reaction time measure where participants have to quickly associate between two target concepts (e.g., Black and White people) and an attribute (e.g., Positive and Negative). When the concept and attributes must be simultaneously selected (e.g., when deciding if a stimulus matches White or Black but where each is also associated with Positive or Negative), then a faster choice in pairing say Black and Negative and White and Positive, compared to Black and Positive with White and Negative, would indicate an implicit racial bias. Such implicit bias is found notwithstanding the explicit attitudes of people, which may not be discriminatory, there being a dissociation between implicit and explicit bias (Greenwald and Krieger, 2006). Indeed, in the explicit racial attitudes test in Peck et al. (2013) there was no evidence of explicit racial bias – although there was implicit racial bias shown in the preexperiment IAT. When it comes to discriminatory behavior, the IAT results have better predictive power in social interaction than explicit measures (Greenwald et al., 2009) – for example, with respect to eye contact, proxemics, and hiring practice (Ziegert and Hanges, 2005; Rooth, 2010). Even though the use and interpretation of the IAT may be controversial, there is evidence supporting its explanatory and predictive power (Jost et al., 2009). With respect to embodiment in a child body, it is known that perception from the perspective of a smaller body results in size overestimations (van der Hoort et al., 2011), and indeed this occurred for both the adult and child conditions in Banakou et al. (2013). However, this does not explain why the overestimation in the child condition was almost double that of the adult condition. Since we have all been children it is possible that the brain relies on autobiographical memory thus making the world appear larger, and more rapidly finds associations between the self and child-like categories. However, with respect to the racial bias study (Peck et al., 2013), none of the participants had ever had dark skin, and yet 12 min of exposure was enough to significantly change their IAT score away from indications of bias. How is this possible? Our answer suggests that the body ownership and agency over the virtual body is more than a superficial illusion, and that it goes beyond the perceptual to influence cognitive processing. It was argued in Banakou et al. (2013); Llobera et al. (2013) that a fundamental mechanism may be through the postulated “cortical body matrix” (Moseley et al., 2012), which maintains a multisensory representation of the space immediately around the body in a body-centered reference frame. The system is responsible for homeostatic regulation of the body, and for dynamically reconstructing the body representation moment to moment based on current multisensory information. It was argued that if, as seems likely, such a system exists, it then operates globally in a hierarchical top-down fashion, so that attribution of the whole body to the self leads to attribution of the body parts to the self. Moreover, it was proposed that it also maintains an overall consistency between the multifaceted aspects of self (personality, attitudes, and behaviors) and the body representation. We can view IAT changes as direct evidence of this – changing the body apparently leads to changes in implicit attitudes. We can say that as well as body ownership over a different body leading to changes in implicit attitudes, the documented changes in implicit attitudes are a very strong signal that in fact there has been a change in body ownership. A further study also hints at the likelihood that a change in body ownership can also result in cognitive changes (Osimo et al., 2015), where it was shown that swapping bodies with (virtual) Sigmund Freud led to an improvement in mood after a self-counseling process.23 The use of embodiment and the transformative power that it seems to have is fundamental feature that separates immersive VR from other types of system, and recent scientific results do back up the statement by Jaron Lanier in the quote at the head of this section, said a quarter of a century ago. Virtual reality is especially suitable for the study of spatial representation and spatial navigation. This at the core of the use of VR: to break down the walls of our room, to transport us to another space, a space that we can explore with or without moving (see Section 6). Spatial navigation is useful for a number of areas and purposes: for learning to navigate a certain model space such as a foreign city to be visited, for rehabilitation of spatial abilities after a neurological disorder or brain injury that affected this function, for neuroscience research (to understand the basis of spatial cognition, memory, and sensory processing), for city design, or to treat post-traumatic stress disorder (PTSD) associated with a space, among others. We may want to move around the city of Paris and to become oriented before we travel to the real city. Or we do not plan to go, and we just want to visit virtual Paris. First of all, how do we move around the city? We can move with a joystick. This allows us to navigate easily from our couch, for example. However, this method may not be optimal if we are planning to internalize, to “learn” the spatial map of Paris, which is better achieved if we move our bodies, since this then enhances theta frequencies in the hippocampus (Kahana et al., 1999). We can also navigate by walking-in-place (Slater et al., 1995; Usoh et al., 1999). Another technique for moving through distances that are greater than the physical space in which the participant can move is called “redirected walking,” where, for example, the system takes advantage of participant head turns to rotate the environment more than the head turn – in this way giving people the impression that they had walked in a long straight line when in reality they had walked in a curve or vice versa (Razzaque et al., 2001, 2002), research that is ongoing, e.g., Suma et al. (2015). Or, we could eventually navigate by thought alone if the VR is connected to a BCI (Pfurtscheller et al., 2006). This is an excellent possibility for patients who are completely immobilized since they can feel the freedom of navigating by thought, an experience very positively evaluated by users (Friedman et al., 2007; Leeb et al., 2007) (see Section 6.5). Understanding the brain mechanisms that underlie the generation of internal maps of the external world, the storage (or memory) of these maps, and their use in the form of navigation strategies is an important field in neuroscience (notice that the Nobel Prize in Physiology or Medicine 2014 was shared, one-half awarded to John O’Keefe, the other half jointly to May-Britt Moser and Edvard I. Moser “for their discoveries of cells that constitute a positioning system in the brain,” known as “place cells” and “grid cells”). Many of the associated studies have been carried out in rodents that were navigating in laboratory mazes. But, how can we study navigation in humans? VR navigation has been found to provide a consistent sensitive method for the study of hippocampal function (Gould et al., 2007). The hippocampus is the main brain structure supporting spatial representation, a structure that is larger than average in London taxi drivers, who are famous for learning the map of London in great detail (Maguire et al., 2000). Virtual cities have been used to determine, for example, that we activate different parts of the brain when we do wayfinding versus route following (Hartley et al., 2003), and to identify spatial cognition deficits in disorders such as depression (Gould et al., 2007) or Alzheimer (Cushman et al., 2008). Even though the brain processes underlying spatial navigation in rodents used to be studied in real mazes, in recent years VR for rodents has also become a valuable tool in basic research in neuroscience. This technique allows navigation of virtual spaces while the animals walk in place on a rotating ball, such that their head is stable and their brain can be visualized while they do spatial tasks (Harvey et al., 2009). Even more recent VR systems for rodents allow 2D navigation including head rotations, resulting in the activation of all the same brain mechanisms that had been identified for freely moving animals, while the animals remain static and walking-in-place (Aronov and Tank, 2014). This approach allows detailed observation of specific brain cells during navigation. Since navigation in virtual space can activate the same brain mechanisms as navigation in the real world, spatial “presence” can be successfully generated (Brotons-Mas et al., 2006; Wirth et al., 2007). The illusory sensation of spatial presence allows the recreation of all the sensations associated with a particular place by using VR, which is useful in order to treat PTSD associated with a space. This has been widely used with soldiers that had been in Iraq and Afghanistan (Rizzo et al., 2010). Virtual spaces such as virtual Iraq, and in particular virtual navigation, have also been used for assessment and rehabilitation following traumatic brain injury, a lesion also frequent in soldiers (Reger et al., 2009). Assessment tasks and training tasks for rehabilitation often go hand in hand, and thus retraining in topographical orientation, wayfinding, and spatial navigation in VR is often used in cognitive rehabilitation following traumatic brain injury, neurological disorders (Bertella et al., 2001; Koenig et al., 2009; Kober et al., 2013). Furthermore, it has been proposed that sustained experiential demands on spatial ability carried out in VR protect hippocampal integrity against age-related decline (Lovden et al., 2012). Virtual reality can be used to study the strategies that humans use for spatial navigation, which reveals the underlying geometry of cognitive maps. These maps could have a Euclidean structure preserving metrics and angles or a topological graph structure. To study this, experiments in the VENLab24 (Rothman and Warren, 2006; Schnapp and Warren, 2007) included a large area that allowed tracked displacements while in VR. A virtual environment representing a virtual hedge maze allowed identification of the location of certain landmarks. By creating two “wormholes” that rotate and/or translate a walker between remote places in the virtual hedge maze, they made the space non-Euclidean, in order to explore the navigational strategies used by different subjects. This is a good example of how VR can be used in this domain to achieve things that are impossible in reality. The study of navigation and wayfinding in VR has a long history. A good starting point for those interested in following this up is the special issue of the journal Presence – Teleoperators and Virtual Environments, edited by Darken et al. (1998). There is a difference between techniques for navigating effectively within a virtual environment, and the extent to which learning wayfinding through a space in a virtual environment transfers to real-world knowledge. Darken and Goerger (1999) pointed out that while the use of VR seems to produce the best results in terms of acquiring spatial knowledge of a terrain, when it comes to actual performance VR training often does not transfer, and can even make the situation worse. The authors, based on a number of studies, concluded that using specific VR techniques (e.g., a virtual compass) and relying on specific virtual imagery during the learning process does not transfer well to real-world wayfinding. However, those who use the VR to rehearse what they will later do in reality, to make a plan, without relying on detailed cues but rather transferring their experience into more abstract spatial knowledge do a lot better. Ruddle et al. (1999) carried out a direct comparison between navigation on a desktop system compared to a head-tracked HMD. They found that although there were no differences in task performance between the two systems in the sense of measuring the distance traveled, the HMD users stopped more frequently to look around the scene and were able to better estimate straight line paths between waypoints. On the other hand, those using the desktop system seemed to develop a kind of tunnel vision. This difference between the two illustrates that in immersive VR there is generation of the types of kinesthetic and proprioceptive cues, i.e., body-centered perception – contributing to what we referred to earlier as natural sensorimotor contingencies for perception – that improve the chance of transfer of knowledge to real-world task behavior. Ruddle and Lessels (2009) carried out a further study where they compared navigation task performance in a virtual environment under three different conditions: (1) a desktop interface, (2) an HMD that was tethered, so that although participants could look around, they could not walk, and (3) a wide area tracking system that allowed participants to really walk. They found that in both their reported experiments (which differ in rendering style of the environment) that those who were able to really walk outperformed the other two groups. See also Ruddle et al. (2011b). In fact, it was later found that walking (in this case enabled through an omnidirectional treadmill) clearly resulted in improved cognitive maps of the space compared to other methods (Ruddle et al., 2011a, 2013) as predicted by Brotons-Mas et al. (2006). In this context, it is worth noting that when comparing presence in a virtual environment through a head-tracked HMD, using (1) point-and-click techniques, (2) walking-in-place where the body moves somewhat like walking but not actually walking, and (3) real walking using wide area tracking, Usoh et al. (1999) found that subjectively reported PI (the component of presence referring to the sense of “being there”) was greater for both types of walking compared to the point-and-click technique. On some presence measures, real walking was preferred to walking-in-place, and as would be expected, real walking was the most efficient form of navigation. A recent study by Sauzéon et al. (2015) used a powerwall-based VR system to test the effect on episodic memory of a virtual apartment. Participants had two methods for navigation through the apartment, either passively watching or using a joystick to actively explore. It was found that episodic memory was superior in the active condition. A similar setup using a virtual model of the city of Tübingen was shown to be advantageous in helping stroke patients to recover some wayfinding ability (Claessen et al., 2015). In a very famous experiment in 1963, Held and Hein (1963) took 10 pairs of neonatal kittens and arranged that 1 navigated an environment by actively moving around it, but the second was carried along passively in a basket by movements of the first. They found that the kittens that were passively moved around, although in principle subject to the same visual stimuli as the active ones, developed significant visual-motor deficits. The authors concluded that “self produced movement with its concurrent visual feedback is necessary for the development of visually-guided behavior.” A similar observation was obtained in rats while walking versus being driven in a toy car (Terrazas et al., 2005), while simultaneous brain recordings were obtained, and the spatial information carried per neuronal spikes in place cells was found to be smaller in the passive navigation. This type of finding fits very well with findings in human studies in virtual environments. The conclusion from these studies is that simply putting someone in a VR in order to learn a particular environment can be effective provided that the form of locomotion includes active control by the participant. Concomitant with our views that the most important factor behind PI is the affordance by the system of perception through natural sensorimotor contingencies, the more that the whole body can be involved in the process of locomotion, the better the result in transfer to the real world, and the formation of cognitive maps. This is an important and vitally important area of research, and above, we have scratched the surface. As VR becomes used on a mass scale, one of its most frequent uses will probably be for virtual travel. If people simply use VR to observe an environment then the form of interface for navigation does not matter much – other than adhering to excellent user interface principles suitable for VR: of greater interest are the sights and sounds encountered. However, if people want to use it for rehearsal, to learn about how to get from A to B, then they had better use a form of body-centered interface, at least equivalent to walking-in-place, but preferably one of the new generation of treadmill interfaces that are currently in development. Immersive VR visualization and interaction with data is relevant for scientific evaluation and also in the fields of training and education. It also allows an active interaction with the representations, e.g., in drug design (see below). We can walk through brains25,26 or molecules, and we can fly through galaxies. The requirements and level of interaction will vary depending on whether this “walk” is for professional use, for students, or for the general public. Immersion in the data could take place alone or in a shared environment, where we explore and evaluate with others. The data could be static, or we could be immersed in dynamic processes. The data should be viewable in multiscale form. Three-dimensional representation of real or modeled data is important for understanding data and for decision-making following this understanding, a relevant topic for a number of fields, especially at this time of exponentially growing datasets. Even when most of the analysis tools are computer-run algorithms, human vision is highly sensitive to patterns, trends, and anomalies (van Dam et al., 2002). There is a substantial difference between looking at 3D data representations on a screen and being immersed in the data, navigating through it, interacting with it with our own body, and exploring it from the outside and the inside. It is logical to expect that when VR commercial systems are pervasive, there will be a trend for currently used 3D data representations on a flat screen to be visualized in immersive media. This, along with the body-tracking systems, will allow a more natural interaction with the data. The extent to which this interaction with data goes further than the “cool” effect and adds real value to the comprehension, evaluation, and subsequent decisions taken as a result is an important issue to explore. It is also important to identify ways to maximally exploit the potential of this data immersion capability. Specific examples of VR for data visualization include molecular visualization and chemical design. In a recently described system called the “Molecular Rift,” the immersive 3D visualization of molecules is combined with interaction with molecules based on gesture-recognition (Norrby et al., 2015). In this version, participants were immersed into protein–ligand complexes. The system was evaluated by groups with experience in medical chemistry and drug design, and the study was focused on the improvement of the user-interaction with the molecules based on gestures and not in the evaluation of improved performance of drug design or specific tasks. Out of 14 users, all of them found the system potentially useful for drug design, and they enjoyed using it, while none experienced motion sickness. A more specific task in interaction with molecules was tested by Leinen et al. (2015). In this study, a task of manipulating nanometer-sized molecular compounds on surfaces was tested under usual scanning probe microscopy versus immersive visualization through an Oculus Rift HMD. The hand-controlled manipulation for extracting a molecule from a surface was improved by the visual feedback provided by immersive VR visualization: preestablished 3D trajectories were followed with higher precision, and deviations from them were better controlled than in immersive than in non-immersive systems (Leinen et al., 2015). Moving from the nanoscale to the microscale, a specific task consisting of the evaluation of the spatial distribution of glycogen granules in astrocytes (glial cells, a type of brain cells) was evaluated in an immersive environment in a Cave-like system (Cali et al., 2015). A section of the hippocampus of 226 μm3 at a voxel resolution of 6 nm was 3D reconstructed based on electron microscopy image stacks. A set of procedures and software was developed to allow such immersive reconstruction. The distribution of glycogen granules initially appeared to have a random distribution, but they were discovered to be grouped into clusters of various sizes with particular spatial relationships to specific tissue features. The authors found the immersive evaluation of the 3D structure to be pivotal to identify such non-random distribution (Cali et al., 2015). The use of an interactive VR room also allowed multiple users to share and discuss the evaluation of the cellular details. In this study there were, however, no comparisons between task performance across different display media. A comparison across three different media – 3D reconstructions rendered on (1) a monoscopic desktop display, (2) a stereoscopic visual display on a computer screen (fishtank), and (3) a Cave-like system – was carried out by Prabhat et al. (2008). In this study, confocal images of Drosophila data: the egg chamber, the brain, and the gut, were evaluated by subjects who had to describe or quantify specific features mostly related to spatial distribution or colocalization and geometrical relationships. A more immersive environment was preferred qualitatively by subjects, and task performance was also superior. Immersive VR is of great value for surgery training, an aspect that is developed in Section 2.4 where specific examples are described. Visualization of the human body from an immersive perspective can provide medical students an unprecedented understanding of anatomy, being able to explore the organs from micro to macro scales. Furthermore, immersive dynamic models of body processes in physiological and pathological conditions would result in an experience of “immersive medicine.” Large-scale coordinated efforts to understand the brain are under way in projects such as the European Human Brain Project27,28 and BRAIN29 Initiative of the United States. These projects are generating detailed multiscale and multidimensional information about the brain. Immersive VR will have a role in the visualization of these brain reconstructions or of the simulations built based on the experimental data. The Blue Brain Project (predecessor of the Human Brain Project) has already generated a full digital reconstruction of a rat slice of somatosensory cortex with 31,000 neurons based on real neurons, and 37 million synapses (Markram et al., 2015). This simulation generates patterns of neuronal activity that reproduce those generated in the brain and is amenable of immersive exploration into the structure and function of the brain. Considering now a larger spatial scale, astronomical visualization in immersive VR has also been explored, both for professional and educational purposes (Schaaff et al., 2015). These authors represented high-resolution simulations of re-ionization of an Isolated Milky Way-M31 Galaxy Pair, with various different representations. It is interesting for education that information can be added to the immersive displays. There is an exciting perspective in the scientific and data visualization area that will open new doors to our understanding. It will be important to evaluate the extent to which immersion and interaction with data results in a more thorough, intuitive, and profound understanding of structures and processes. But in any event, once this route is open, visualization of 3D models on a flat screen will feel like watching Star Wars on a small black and white TV (see Presentation S1 in Supplementary Material). Isaac Asimov’s novels Fantastic Voyage (1966),30 based on the movie of the same name,31 and Fantastic Voyage II: Destination Brain (1987)32 portrayed a situation with humans shrunk to microscopic scale entering into the body of a patient. VR and the detailed human body scans that now exist make this possible (of course in virtual reality). McGhee et al. (2015) have used the “fantastic voyage” approach to support education of stroke patients about their condition by allowing them to move through a brain representation using the Oculus Rift HMD. The area of application of VR in education is vast. For recent reviews, see Abulrub et al. (2011), Mikropoulos and Natsis (2011), Merchant et al. (2014), and Freina and Ott (2015). There are several reasons why VR is an excellent tool for education. First, it can change the abstract into the tangible. This could be especially powerful in the teaching of mathematics. For example, Hwang and Hu (2013) suggest that the use of a collaborative virtual environment has advantages for students learning geometrical concepts compared to traditional paper and pencil learning. However, it is not completely clear which type of VR system was used, although it appears to be of the desktop variety. Kaufmann et al. (2000) describe an HMD-based augmented reality system that provides a learning environment for spatial abilities including concepts from vector algebra. They provide anecdotal evidence for the effectiveness of the method. Roussou (2009) reviews the teaching of mathematics in VR using a “virtual playground”33,34 and in particular describes an experiment on learning how to compare fractions by 50 children of between 8 and 12 years in a Cave-like system (Roussou et al., 2006). In a between-groups experiment, there were three conditions – children who learned using active exploration of the scenario (n = 17), those who used the virtual playground but who learned by passively observing a friendly virtual robot (n = 14), and another group who did not use VR but rather a Lego-based method (n = 19). Quantitative analysis of the results found no advantage to any system. A detailed qualitative analysis, however, suggested that the passive VR condition tended to foster a reflective process among the children, and great enjoyment in interacting with the robot, associated with better understanding. The second advantage of VR in education is, notwithstanding the results of the virtual playground experiment, that it supports “doing” rather than just observing. One example of this is surgical training (see Section 2.4), for example, one review emphasizes how VR is increasingly used in neurosurgery training (Alaraj et al., 2011), ideally in conjunction with a haptic interface (Müns et al., 2014). Indeed, a European consensus program for endoscopic surgery VR training has been designed and agreed (van Dongen et al., 2011). For an example in engineering learning see Ewert et al. (2014). The third advantage is that it can substitute methods that are desirable but practically infeasible even if possible in reality. For example, if a class needs to learn about Niagara Falls 1 week, the Grand Canyon the next, and Stonehenge35 the week after, it is infeasible for the class to visit all of those places. Yet, virtual visits are entirely possible, and such environments have been under construction (Lin et al., 2013) including the idea of virtual field trips (Çaliskan, 2011). It has certainly been suggested that immersive VR will change the nature of field trips,36 and although there have been plenty of inventive demonstrations37,38,39 it seems that as yet there have been no studies of the effectiveness of this, although perhaps it is so obviously advantageous that formal studies may be unnecessary. The fourth advantage of VR in education involves breaking the bounds of reality as part of exploration. For example, changing how activities such as juggling would be if there was a small change in gravity, or how it would be to ride on a light beam, a universe where the speed of light were different. These ideas were envisaged and implemented for VR by Dede et al. (1997); however, there has been no more recent follow-up, which could now occur given greater availability of VR equipment. In this article, we have emphasized that the real power of VR is that it enables approaches that go beyond reality in a very fundamental way – more than just exploring strange physics. An example of this in the field of education was provided by Bailenson et al. (2008), concerned with the delivery of teaching rather than the content. In a collaborative virtual environment, it is possible to arrange the virtual classroom so that every student is at the center of attention of the teacher, and where the teacher has feedback about which students are not receiving enough eye gaze contact. Additionally, virtual colearners who could be either model students or distracting students can influence learning, and the results overall showed that these techniques do improve educational outcomes. Bailenson and Beall (2006) referred to this type of technique as “transformed social interaction.” Overall, for the reasons we have given, and no doubt others, VR is an extremely promising tool for the enhancement of learning, education, and training. We have not mentioned other possibilities such as music or dance, or various dexterous skills, but for these areas VR has clearly great potential. Within the area of VR for training, surgical training has been a thoroughly investigated field (Alaraj et al., 2011). The use of simulations in surgical planning, training, and teaching is highly necessary. To give an illustrative example of why VR is necessary for surgery: interventional cardiology has currently no other satisfactory training strategy than learning on patients (Gallagher et al., 2005). It seems that acquiring such training on a virtual human body would be a better option. In the training of medical students and in particular of surgeons, there is a relevant potential role for VR as a tool to learn anatomy through virtual 3D models. Even though there are studies trying to evaluate how useful VR can be to improve the learning of anatomy (Nicholson et al., 2006; Seixas-Mikelus et al., 2010; Codd and Choudhury, 2011) – including studies proposing that VR could replace the use of corpses in medical school – fully immersive and interactive systems have hardly been used up to now. Most of the 3D models used so far are for screen displays. Still, even the visualization of non-immersive 3D body models to study anatomy yields good results for learning, and therefore this is an area that should expand in the future, integrating fully immersive systems and different forms of manipulation and interaction of the trainees with the body models. One of the first publications of VR in the field of surgery was on VR-hepatic surgery training, and the words “Surgical simulation and virtual reality: the coming revolution” were on the title of both the article (Marescaux et al., 1998) and the editorial (Krummel, 1998) in the Annals of Surgery nearly 20 years ago. However, the revolution has not happened yet, although the field is now ready for this possibility. Surgical training in VR requires a combination of haptic devices and visual displays. Haptic devices transmit forces consisting of both the forces exerted by the surgeon and a simulation of the forces and resistances of the various body tissues. A critical question is whether the skills acquired in a virtual training are successfully transferred to the real world of surgery. Seymour et al. (2002), in a highly cited article, provides one of the first demonstrations that this is the case. The performance of laparoscopic cholecystectomy gallbladder dissection was found to be 29% faster for VR-trained versus classically trained surgeons, while errors were six times less likely to occur in the VR-trained group. The system used though (Minimally Invasive Surgical Trainer-Virtual Reality – MIST VR system – Mentice AB, Gothenburg, Sweden), was a 2D representation on a screen of a haptic system used for simulated surgery. These results are likely to improve with a more immersive system. To illustrate the value given to surgical training in VR, an FDA panel voted in August 2004 to make VR simulation of carotid stent placement an important component of training. In the same month, the Society for Cardiovascular Angiography and Interventions, the Society for Vascular Medicine and Biology, and the Society for Vascular Surgery all publicly endorsed the use of VR simulation in carotid stent training (Gallagher and Cates, 2004). The most common uses so far of VR for surgical training have been those of laparoscopic procedures (Seymour et al., 2002), carotid artery stenting (Gallagher and Cates, 2004; Dawson, 2006), and ophthalmology [Eyes Surgical, based on Jonas et al. (2003)]. In general terms, a large number of studies – out of which only a few seminal ones are cited here – coincide in finding positive results of VR training. Most of the systems mentioned above concentrate on the local surgical procedure, e.g., how to place a stent or dissect the gallbladder. However, the reality in a surgery room is more complex, and the surgery may need to be performed in situations where the patient’s physiological variables are not stable, or there can be a hemorrhage, or even a fire in the surgical theater. The response of the surgical team to these situations will be critical for the well-being of the patient, and immersive VR should be an optimal frame for such training. VR can embed the specific surgical procedure, for example, the placement of the carotid stent, into various contexts and under a number of emergency situations. In this way, during training, not only the contents but also the skills and the experience of being in a surgery room for many years can be transmitted to the trainees, which can include not only surgeons but all the sanitary personnel, each in their specialized roles. There is a huge explosion of research in the effectiveness of VR-based training for surgery including meta-analyses and reviews (Al-Kadi et al., 2012; Zendejas et al., 2013; Lorello et al., 2014), transfer of training (Buckley et al., 2014; Connolly et al., 2014), and many specialized applications (Arora et al., 2014; Jensen et al., 2014; Singh et al., 2014). This is likely to be a field that expands considerably. Here, we broadly address issues relating to physical training and improvement through sports and exercise, an area of growing interest to professional sports. In the 1990 SIGGRAPH Panel (Barlow et al., 1990), Jaron Lanier mentioned the idea of being able to play table tennis (ping-pong) with a remote player using networked VR. Of course this is now possible40 and is certain to be readily available in the near future. For example, a version has been implemented using two powerwall displays plus tracking for each player (Li et al., 2010). However, the opponent need not be a remote player in a shared VR but may be a virtual character. Immersive VR, at least with hand tracking if not full body tracking, has ideal characteristics for playing table tennis or other competitive sports, with the possible advantage of not having to spend time traveling to the gym. There are several areas where VR can provide useful advantage for sport activities. First, for leisure and entertainment reasons – such as the table tennis example above. Second, for learning, training, and rehearsal. To the extent that VR supports natural sensorimotor contingencies at high enough precision, it could be used for these purposes. However, here it would be important to carry out rigorous studies to check in case small differences between the VR version and the real version might lead to poor skills transfer, or incorrect learning. For example, learning to spin or slam in table tennis requires very fine motor control depending on vision, proprioception, vestibular feedback, tactile feedback, force feedback, even the movement of air, and the sound of the ball hitting the table and the bat. Hence, to build a virtual table tennis that is useful for skill acquisition or improvement must take into account all of these factors, or the critical ones if these are known. On the other hand, virtual table tennis could be thought of as a game in its own right and nothing much to do with the real thing. In this case, virtual table tennis would fall under the first category – entertainment and leisure. Additionally, as we will see in Section 6.3 in the context of acting rehearsal, although VR misses fine detailed facial expression that is critical for successful acting, it is nevertheless useful for that aspect of rehearsal known as “blocking,” which is concerned more with overall spatial configuration of the actors in the scenario. Similarly, even without being able to reproduce all the fine detail necessary for the transfer of training skills to reality, VR may be useful in team sports to plan overall strategy and tactics. A third utility of VR in sports is for rehabilitation following injury. We will briefly consider some of these areas. In a comprehensive review of VR for training in ball sports Miles et al. (2012) analyze eight challenges: effective transfer of training, the types of skills best learned in VR, the technologies that result in the best quantifiable performance measures, stereoscopic displays have both advantages and disadvantages (e.g., vision is not the same as in real life) – under which conditions should they be used?, the role of fidelity – to what extent and under what conditions is it important?, what kind of feedback should be delivered to the learner, how and when is feedback appropriate?, the effectiveness of teaching motor skills in the inevitable presence of latency and inaccuracies of representation, and finally, cost. The review points out several inevitable hurdles that must be overcome. For example, in training for field games such as American Football or soccer, the area of play is huge compared to the effective space in which someone in a VR system can typically move. A play on a field may involve running 25 m, whereas the effective area of tracking is say 2 m around a spot where the participant in VR must stand. Clearly, using a Wand to navigate or even a treadmill may miss critical aspects of the play (see also Section 2.1.3 for a brief discussion of different methods of moving through a large virtual environment). The paper reports many such pitfalls that need to be overcome and points out that studies have been inconclusive and therefore, there is the need for more research. Craig (2013) reviews how VR might be used to understand perception and action in sport. She argues that VR offers some clear advantages for this and gives a number of examples where it has been successful, as well as pointing out problems. However, she wonders why if it is successful it has not been widely used in training up to now, but where there is reliance on alternatives such as video. She points out that one problem has been cost, though this is likely to be ameliorated in the near term. A second problem is to effectively and differentially meet the needs of players and coaches, pointing out how VR action replays could be seen from many different viewpoints, including those of the player and of the coach so that different relevant learning would be possible. Another advantage of VR would be to train players to notice deceptive movements in opponents, by directing attention to specific moves or body parts that signal such intentions. However, she points out as mentioned above how it is critical to provide appropriate cues to avoid mislearning. Ruffaldi et al. (2011) examined the theoretical requirements for successful training transfer in the context of rowing and described a haptic-enabled VR system with a single large screen for visual feedback. Rauter et al. (2013) described a different VR simulator for rowing. This was a Cave-like system enhanced with auditory and haptic capabilities, an earlier version described in von Zitzewitz et al. (2008). Their study, carried out with eight participants, compared skill acquisition between conventional training on water, with training in the simulator. Examining the differences between the two they concluded that both with respect to questionnaire and biomechanical responses that the methods were similar enough for the simulator to be used as a complementary training tool, since there was sufficient and appropriate transfer of training using this method. Wellner et al. (2010b) described an experiment where 10 participants took part in simulated rowing. The novelty was that they added a virtual audience to test the idea that the presence of an audience would encourage the rowers in a competitive situation. They did not find a notable outcome in this regard, only the relatively high degree of presence felt by the participants. On similar lines, Wellner et al. (2010a) examined whether the presence of virtual competitors in a rowing competition would boost performance. No definite results were found, but according to the authors, the study had some flaws, and in any case the sample size was small (n = 10). In spite of null results, it is important to note how VR affords the possibility to experiment with such factors that would be possible, but logistically very difficult to do in reality. Another example of this use of VR that is logistically very difficult to do otherwise is for spectators to attend sports matches when they cannot physically attend (e.g., someone in the US who is a fan of English soccer). Instead, they can view them, as if they were there – and have the excitement of seeing the game life-sized, first hand, and among a crowd of enthusiasts. Kalivarapu et al. (2015) implemented a system to display American Football in a high-resolution, six-sided, Cave-like system and also in an Oculus DK2 HMD. They carried out a study with 60 participants who were divided into three conditions: Cave (n = 20), HMD (n = 20), and video (n = 20), where the game and associated events were shown on video. They concluded that the Cave and HMD experiences gave the participants greater opportunity to interact (i.e., view from different vantage points) compared to the video. Participants nevertheless experienced a greater degree of realism in the Cave, perhaps not surprising because of its greater resolution (and several orders of magnitude greater cost). On the whole, the HMD and Cave produced similar results across a number of aspects of presence. There is a growing interest in the use of VR for sports viewing and other events, mainly using 360° video. See also the “Wear the Rose” system that gives fans the chance to experience rugby games first hand,41,42,43,44 and an example of its use in American Football.45 There have been many other applications of VR in sports – impossible to cover all of them here – for example, a baseball simulator,46 for handball goalkeeping (Bideau et al., 2003; Vignais et al., 2009), skiing (Solina et al., 2008), detecting deceptive movements in rugby (Brault et al., 2009; Bideau et al., 2010), and pistol shooting47 (Argelaguet Sanz et al., 2015), among others. A special issue of Presence – Teleoperators and Virtual Environments was devoted to VR and sports (Vignais et al., 2009; Multon et al., 2011), which would be a good starting point for readers wishing to follow up this topic in more detail (see Presentation S2 in Supplementary Material). It is well known that aerobic exercise is extremely good for us, especially as we age. A meta study of research relating to older adults carried out by Colcombe and Kramer (2003) showed that there is a clear benefit for certain cognitive functions. A more recent survey by Sommer and Kahn (2015) again showed the benefits of exercise for cognition for a variety of conditions. Yu et al. (2015) showed its utility for Alzheimer patients and Tiozzo et al. (2015) for stroke patients. However, repetitive exercise with aerobic benefits can be boring; indeed, Hagberg et al. (2009) found in a study that enjoyment is important in increasing physical exercise. Virtual reality opens up the possibility of radically altering how we engage in exercise. Instead of just being on a stepping machine watching a simple 2D representation of a terrain, we can be walking up an incline on the Great Wall of China, or walking up the steps in a huge auditorium where we are excitedly going to watch a sports game, or even walking up steps to a fantasy castle in a science fiction scenario. Instead of just riding an exercise bike, we can be cycling through the landscape of Mars.48,49,50 One use of VR for exercising would be an extension of approaches that have already been tested, normally referred to as “exergaming.” This involves, for example, connecting an exercise bike to a display, so that the actions of the rider affect what is displayed, e.g., faster pedaling leads to corresponding depiction of increased optic flow on the display. Moreover, other motivational factors can be introduced such as virtual competitors (as we saw in the rowing example above). Anderson-Hanley et al. (2011) carried out a study with n = 14 older adults using a cybercycle (an exercise bike with a screen in front) and competitive avatars as in a race.51 Their evidence suggested that this social factor tended to increase participants’ effort. Finkelstein and Suma (2011) used a three-walled stereoscopic display and upper body tracking of participants who had to dodge virtual planets flying toward them. Their experiment included n = 30 participants who played for 15 min. They found that the method produces increased heart rate (i.e., is aerobic) and motivates children and adults to exercise. Mestre et al. (2011) had n = 12 participants in an experiment that used an exerbike (with a large screen) where they compared video feedback with video and music feedback. They found that the addition of music was beneficial both psychologically (for motivation and pleasure) and behaviorally. Anderson-Hanley et al. (2012) carried out a formal clinical trial where they used “cybercycling,” as above, stationary cycling tied to a screen display, with older people (n = 102). They were interested in testing among other things whether such cycling would improve executive function. They found that cognitive function was improved among the cybercyclers, and that it was likely that it would help to prevent cognitive decline compared to traditional exercise. Overall, while there has been significant work in this area, a systematic review carried out by Bleakley et al. (2013) found that although these types of approach are safe and effective, that that there is limited high quality evidence currently available. It is one thing to be cycling or walking on a treadmill or exercise steps while looking at a screen, since this is anyway the case with most exercise machines even though the display may be very simplistic. Since the exerciser is not actually moving through space, looking at a screen should be harmless. However, it is not obvious that the same activities could be safely or successfully carried while people are wearing an HMD, which not only obscures their vision of the real world but may also lead to a degree of nausea – which is all the more likely to occur while moving through virtual space. Shaw et al. (2015b) discussed five major design challenges in this field. First, to overcome the problem of possible sickness; second, to have reliable tracking of the body; third to deal with health and safety aspects; fourth the choice of player visual perspective; and fifth, the problem of latency. They described a system that was designed to overcome these problems, that used an Oculus DK2 HMD, and which was evaluated in an experimental study (Shaw et al., 2015a). This had n = 24 participants (2 females, ages between 20 and 24). They compared three setups: a standard exercise bike with no feedback, the exercise bike with an external display, and the bike with the HMD. The fundamental findings were that on several measures (calories burned, distance traveled) the two feedback systems outperformed the bike only condition but did not differ from each other. The two systems with feedback were also evaluated as more enjoyable than the bike only, and the HMD was more enjoyable and was associated with greater motivation than the external display system. Only 4 out of 26 reported some minor symptoms of simulator sickness. As the authors pointed out, the study was limited, since the participants were almost all males, and with limited age range, and it is not known how well these results would generalize. Bolton et al. (2014) also described a system that combined an Oculus Rift HMD52 with an exercise bike that was designed to reduce the possibility of motion sickness; however, no experimental results were given. There are several other applications without associated papers such as RiftRun53 where participants run on the spot to virtually run through an environment. Overall, as in other fields, there are promising but far from conclusive results, but irrespective of scientific studies it is highly likely that immersive VR will be combined with personal exercise systems, since the relatively low cost now makes this possible, and some sports providers may decide that the “cool” factor makes such an enterprise worth the economic risk. Whether these are successful or not will obviously depend on consumer uptake. Finally, as in other applications, we emphasize that VR allows us to go beyond what is possible in reality. Even cycling through Mars is just cycling. It is physically possible, if highly unlikely to be realized. Perhaps though there are fundamentally new paradigms that can really exploit the power of VR – the virtual unreality that we mentioned in the opening of this article. One approach is to use VR to implicitly motivate people toward greater exercise rather than as a means to carry out the exercise itself. Fox and Bailenson (2009) carried out a study where participants using a head-tracked HMD-based VR saw a virtual character from 3PP (i.e., across the room and looking toward them) with a face that was based on a photograph of their own face and that therefore had some likeness to themselves. Participants at various points were required to carry out physical exercises or not. While they did not carry out these exercises the body of their virtual doppelganger became fatter, and while they did the exercises the virtual body became thinner. There were n = 22 participants in this reinforcement condition, n = 22 in another condition where the virtual body did not change, and n = 19 in another condition where there was just an empty virtual room with no character. The dependent variable was the amount of voluntary exercise that participants carried out in a final phase of the experiment (during which there was also positive and negative reinforcement). It was found that the greatest exercise was carried out by the group that had the positive and negative reinforcement. In order to check that it was the facial likeness that accounted for this result, a second experiment introduced another condition, which was that the face of the virtual body was that of someone else. Here, the result only occurred for the condition of the virtual doppelganger. Finally, it could be argued that the participants in the voluntary exercise phase only exercised to avoid the unpleasant sensation of seeing their virtual doppelganger “gaining weight.” A third study examined participants’ level of exercise during a 24-h period after the conclusion of the study, through a questionnaire returned online. The setup was that they saw their doppelganger exercising on a treadmill, or a virtual character that did not look like themselves exercising, or a condition where their doppelganger was not doing any exercise but just standing around. The results suggested that those who saw their virtual look-alike exercising did carry out significantly more exercise in the real world in a period after the experiment than the other two conditions. A second approach might be to use VR to provide a surrogate for exercising, rather than providing a motivation to exercise physically in reality. Kokkinara et al. (2016) illustrated what might be possible. Participants who were seated wearing an HMD and unmoving (except for their head) saw from 1PP their virtual body standing and carrying out walking movements across a field. They saw this when they looked down directly toward their legs that would be walking, and also in a shadow. In another condition they saw the body from a 3PP. After experiencing this virtual walking for a while they approached a hill, and the body walked up the hill. In the embodied 1PP condition participants had a high level of body ownership and agency over the walking, compared with the 3PP condition. More importantly, for this discussion, while walking up the hill participants had stronger skin conductance responses (more sweat) and greater mean heart rate in the embodied condition, compared to a period before the hill climbing, which did not occur for those in the 3PP. There were 28 participants each of whom experienced both conditions (there was another factor, but it is not relevant to this discussion). Although there are caveats for both of these studies, the important aspect for our present purpose is that they illustrate how VR might be used to break out of the boundaries of physical reality and achieve useful results through quite novel paradigms. Of course it must always be better to carry out actual physical exercise rather than relying on your virtual body to do it for you. Yet sometimes, for example, on a long flight, virtual exercise might be the only possibility. Indeed, in this context, it has been found that participants who perceive their virtual body from 1PP in a comfortable posture are more likely to feel actual comfort than those who see their body in an uncomfortable posture (Bergström et al., 2016).54 The point is that VR has the power to go beyond what we can do in physical reality, even in principle, and become a radically new medium with different ways of thinking and novel ways of accomplishing life-changing goals. There are many areas of social interaction between people where it is important to have good scientific understanding. What factors are involved in aggression of one group against another, or in various forms of discrimination? Which factors might be varied in order to decrease conflict, improve social harmony? It is problematic to carry out experimental studies in this area for reasons discussed below. However, immersive VR provides a powerful tool for the simulation of social scenarios, and due to its presence-inducing properties can be effectively used for laboratory-based controlled studies. Similarly, away from the domain of experiments, there are many aspects of our cultural heritage that people cannot experience – how an ancient site might have looked in its day, the experience of being in a Roman amphitheater as it might have been at the time, and so on. Again, VR offers the possibility of direct experience of such historical and cultural sites and events. In this section, we consider some examples of the application of VR in these fields, starting first with social psychology. Loomis et al. (1999) pointed out how VR would be a useful tool for research in psychology and Blascovich et al. (2002) in social psychology. Here, the potential benefits are enormous. First, studies that are impossible in reality for practical or ethical reasons are possible in VR. Second, VR allows exact repetition of experimental conditions across all trials of an experiment. Moreover, virtual human characters programed to perform actions in a social scenario can do so multiple times. This is not possible with confederates or actors, who can become tired and also have to be paid. Although it is costly to produce a VR scenario, once it is done, it can be used over and over again. Also, the scenarios can be arbitrary rather than restricted to laboratory settings. Rovira et al. (2009) pointed out how the use of VR in social science allows for both internal and ecological validity. The first refers to the possibility of valid experimental designs including issues such as repeatability across different trials and conditions, the precision at which outcomes can be measured, and so on. The second refers to generalizability. For example, in a study of the causes of violence, VR can place people in a situation of violence, which cannot be done in a real-life setting. This means that there is the possibility of generalization of results out of the laboratory to what may occur in reality. In particular, VR can be used to study extreme situations that are ethically and practically impossible in reality. This relies on presence – PI and Psi – leading to behavior in VR that is sufficiently similar to what would be expected in real-life behaviors under the approximately the same conditions. In the sections below, we briefly review examples of research in this area. How do you feel when a stranger approaches you and stands very close? The answer may vary from culture to culture, but at least in the “Anglo-Saxon” world you are likely to back away. Proxemics is the study of interpersonal distances between people, discussed in depth by Hall (1969). He defined intimate, personal, social, and public distances that people maintain toward each other (and these distances may be culturally dependent). An interesting question is the extent to which these findings also occur in VR. If a virtual human character approaches and stands close to you, in principle this is irrelevant since nothing real is happening – there is no one there. Even if the character represents a physically remote actual person who is in the same shared virtual environment as you, they are not really in the same space as you, and therefore not close. We briefly consider proxemics behavior in VR because it is a straightforward but fundamental social behavior, and finding that the predictions of proxemics theory hold true for VR is a foundation for showing that VR could be useful for the study of social interaction. There has not been a great deal of work on this topic that has exploited VR. Bailenson et al. (2001) showed that people tend to keep greater distances from virtual representations of people than cylinders in an immersive VR. This work was continued in Bailenson et al. (2003) where it was shown that participants maintain greater distances from virtual people when approaching them from the front, than from the back, and also greater distances when there is mutual eye gaze. Participants also moved away when virtual characters approached them. Readers might be wondering – so what? This is obvious. It has to be remembered though that these are virtual characters, no real social interaction is taking place at all. Further studies have shown that proxemics behavior tends to operate in virtual environments (Guye-Vuilleme et al., 1999; Wilcox et al., 2006; Friedman et al., 2007). McCall et al. (2009) showed that proxemics behavior can be used as a predictor of aggression. Proxemics distances of n = 47 (mainly self-identified as White) participants were measured from two White or two Black virtual characters. Subsequently, participants engaged in a shooting game with those virtual characters. It was found that there was a positive correlation between the distance maintained from the characters in the first phase and the degree of aggression exhibited toward them in the second phase but only for the condition where both virtual characters were Black. Llobera et al. (2010) examined proxemics in immersive VR by measuring how skin conductance response varied with the approach of one or multiple virtual characters toward the participant, to different interpersonal distances. This was to test the finding of McBride et al. (1965) of a relationship between proximity and heightened skin conductance. It was found that there was a greater skin conductance response as a function of the closeness to which the characters approached participants and the number of characters simultaneously approaching. However, it was found that there was no difference in these responses when cylinders were used instead of characters. It was suggested that skin conductance cannot differentiate between the arousal caused by characters breaking social distance norms and the arousal caused by fear of collision with a large object (the cylinder) moving close to the participants. Kastanis and Slater (2012) showed how a reinforcement learning (RL) agent controlling the movements of a virtual character could essentially learn proxemics behavior in order to realize the goal of moving the participant to a specific location in the virtual environment. Participants in an immersive VR saw a male humanoid virtual character standing at a distance and facing them. Every so often the character would walk varying distances toward the participant, walk away from the participant, or wave for the participant to move closer to him.55 The RL behind the character gained a positive reward every time the participant stepped backwards toward a target position. The long run aim was to get the participant to move far back to this target, unknown to the participant herself. The RL eventually learned that if its character went very close to the participant, then the participant would step backwards. Moreover, if the character was far away then it sacrificed short-term reward by simply waiving toward the participant to come closer to itself, because then its moving forwards action would be effective in moving the participant backwards. Hence, the RL relied on presence (the participant moving back when approached too close – from the prediction of proxemics theory) and learned how to exploit this proxemics behavior to achieve its task. For all participants, the RL learned to get the participant back to the target within a short time. This method could not have worked unless proxemics occurred in the VR. Having shown that this is the case we move on to more complex social interaction. Research suggests that VR can provide insights into discrimination by affording the opportunity for people to have simulated experiences of the world through another group’s perspective even if only briefly. For example, we saw earlier how simply placing White people in a Black body in a situation known to be associated with race discrimination led to an increase in implicit racial bias (Groom et al., 2009). On the other hand, virtual body representation has been shown to be effective with respect to racial bias, where White people embodied in a Black-skinned body show a reduction in implicit racial bias (Peck et al., 2013)56 in a neutral social situation as we saw in Section 2.1.2. More generally, the method of virtual embodiment has also been used to give adults the experience of being a child (Banakou et al., 2013), has been shown to affect motor behavior while playing the drums (Kilteni et al., 2013), and has been used to give people the illusory sensation of having carried out an action that they had in fact not carried out (Banakou and Slater, 2014). Some of the work in the area of body representation applied to implicit bias is reviewed in Slater and Sanchez-Vives (2014) and Maister et al. (2015). A further question is whether embodied experiences as an “outgroup” member will actually translate into different behavior toward members of the group. Although not in the context of discrimination there is some evidence from the work of Ahn et al. (2013) that this might be the case. They immersed people with normal vision into an HMD-delivered VR where they experienced certain types of color blindness. In three experiments (N = 44, N = 97, and N = 57), they compared the effects of perspective taking where participants simply imagined being color blind to a condition where the display actually made them color blind in the virtual environment. They found that indeed the VR experience did result in greater helping behavior of participants toward color blind people both within the experiment and in their behavior after the experiment (with a moderate effect size of the squared multiple correlation of around 10%). It illustrates how VR might be used to put people experientially in situations and how this may influence their behavior compared with only imaginal techniques. Stanley Milgram carried out a number of experiments in the 1960s designed to address the question of how events such as the Holocaust could have occurred (Milgram, 1974). He was interested in finding explanations of how ordinary people can be persuaded to carry out horrific acts. The type of experiments that he conducted involved experimental subjects giving apparently lethal electric shocks to strangers. These are a very famous experiments that are as topical today as in the 1960s, and barely a week goes by when there is not some mention of it in news media,57 or further research relating to it is reported.58 There were several different variants of the experiment that Milgram designed. Typically, the experimental subject, normally recruited from the local town (near Yale University) rather than from among psychology students, were invited to the laboratory where he or she met another person, also supposedly recruited in the same way. The other person was in fact a confederate of the experimenter, an actor hired for the purpose, this being unknown to the subject. The experimenter invited the subject and the actor to draw lots to determine their respective roles in the experiment. It turned out that the subject was to play the role of Teacher, and the actor the role of Learner, but the outcome of this draw was fixed in advance. Then both the Teacher (subject) and Learner (actor) were taken to another room, where the Learner had electrodes placed on his body connected to an electric shock machine. It was explained that the idea was to examine how punishment might aid in learning. The Learner was to learn some word-pair associations, and whenever he gave a wrong answer he was to be shocked. The Learner, acting in a jovial manner, explained that he had a mild heart condition, and the experimenter assured both Learner and Teacher that “Although the shocks may be painful they are not dangerous.” There are online videos showing the original experiment.59 The Learner was left in the room, and the experimenter took the Teacher back into the main laboratory, closing the door to that room. He explained to the Teacher that he had to read out cues for the word-pair tests and whenever the Learner gave the wrong answer the Teacher should increase the voltage on a dial and administer an electric shock at that voltage. The voltages were labeled from 15 V (slight shock) to 375 V (danger: severe shock) to 450 V (marked “XXX”). During the course of the experiment, a tape was played giving the responses of the Learner. With the low voltage shocks there was no response. After a while though the Learner could be heard saying “ouch!” and as the voltage increased further he complained more and more vociferously, eventually saying that he had the heart condition and that his heart was starting to bother him. He shouted that he wanted to be let out of the experiment, and finally with the strongest shocks he became completely silent. If at any point the Teachers said that they felt uncomfortable or that they wanted to stop, the experimenter would say one of “The experiment requires that you continue,” “It is absolutely essential that you continue,” or “You have no other choice, you must go on” in a prescribed sequence. Participants generally found that the experience was extremely stressful, and even if they continued through to lethal voltages they were clearly very upset. Prior to the experiment, Milgram had asked a number of psychologists about how many people would go all the way and administer even lethal voltages to the Learner. The view was that only a tiny minority of people, those with psychopathic tendencies, would do so. In the version of the experiment described above, about 60% of subjects went all the way to administer the most lethal shocks. The results stunned the world since it apparently showed that ordinary people could be led to administer severe pain to another at the behest of an authority figure. There is a wealth of data and analysis and a description of many different versions of this experiment in Milgram (1974), but the basic conclusion was that people will tend to obey authority figures. Here, ordinary people were being asked to carry out actions in a lab in a prestigious institution (Yale University) and in the cause of science. They tended to obey even if they found that doing so was extremely uncomfortable. Although this is not the place for discussion of this interpretation, interested readers can find alternative explanations for the results in, for example, Burger (2009); Miller (2009); Haslam and Reicher (2012); and Reicher et al. (2012). Participants in these experiments were deceived – they were led to believe that the Learner was really just another subject, a stranger, and that he was really receiving the electric shocks. The problem was not so much the stress, but that fact that participants were not informed about what might happen, were not aware that they may be faced with an extremely stressful situation, and were ordered to continue participating even after they had clearly expressed the desire to stop. These and other issues led to strong criticism from within the academic community that eventually led to a change in ethical standards – informed consent, the right to withdraw from an experiment at any moment without giving reasons, and care for the participants including debriefing. See also a discussion of these issues as they relate to VR in Madary and Metzinger (2016). Hence, these experiments on obedience, no matter how useful, cannot be carried out today for research purposes, no matter how valuable they might seem to be scientifically. Yet, the questions addressed are fundamental since it appears that humans may be too ready to obey the authority of others even to the extent of committing horrific acts. In 2006, a virtual reprise of one version of the Milgram experiments was carried out (Slater et al., 2006), with full ethical approval. The approval was given because participants were warned in advance about possible stress, could leave the experiment whenever they wanted, and of course they knew for sure that no one in reality was being harmed because in this experiment the Learner was a (poorly rendered) virtual female character displayed in a Cave-like VR setting.60 The participants (Teachers) sat in the Cave system by a desk on which there was an electric shock machine. They saw the virtual Learner on the other side of a (virtual) partition, projected in stereo on the front wall of the Cave. They went through the same routine with the virtual Learner as in Milgram’s experiment, reading out cue words, and administering “electric shocks” to the virtual Learner whenever she answered with an incorrect wrong word-pair association. Just as in the original experiment, after a while she began to complain and demanded to be let out of the experiment, and eventually seemed to faint. However, if participants expressed a wish to stop, no argument against this was given, and they stopped immediately. Even though carried out in VR, many of the same results as the original were obtained, though at a lower level of intensity of stress. There were n = 34 participants, 23 of whom saw and heard the virtual Learner throughout the experiment, and 11 who saw and spoke to her initially but then a curtain descended, and they only communicated with her through text once the question and answer session began. All those who communicated by text gave all of the shocks. However, 6 of the 23 who saw and heard the Learner withdrew from the experiment before giving all shocks. In other words, 74% continued to the end, in spite of the fact of feeling uncomfortable, as was shown by their physiological responses (skin conductance and electrocardiogram responses). In the paper, it was argued that the gap between reality and VR makes these types of experiments possible. Presence (PI and Psi) leads to participants tending to respond to virtual stimuli as if they were real. But, on the other hand, they know that it is not real, which can also dampen down their responses. In debriefing, when participants were asked why they did not stop even though they felt uncomfortable, a typical answer was “Since I kept reminding myself that it wasn’t real.” From the original experiments of Stanley Milgram we know (at least for the 1960s around Yale in the US) how people actually responded. In VR, we see that they responded similarly, though not with the very strong and visible stress that many of the original participants displayed. Using VR, we can study these types of events, and how people respond to them, and construct predictive theory that may help us understand how people might respond in reality. The predictions can then be tested against what happens in naturally occurring events and the theory examined for its viability. This type of approach can also be used to gather real-time data about brain activity of people when faced with such a situation (Cheetham et al., 2009). You are in a bar or other public place and suddenly a violent argument breaks out between two other people there. It seems to be about something trivial. One man is clearly the perpetrator, and the victim is trying to calm down the situation, but his every attempt at conciliation is used by the perpetrator as a cue for greater belligerence. Eventually the perpetrator starts to physically assault the victim. What do you do? Suppose you are alone there? Suppose there are other people? Perhaps the victim shares some social identity with you, such as being a member of the same club or same ethnic group different to that of the aggressor. How do you respond? Do you try to intervene to stop the argument? Or walk away? How is your response influenced by these factors such as number of other bystanders or shared social identity with the victim or aggressor? This area of research was initiated in the late 1960s provoked by a specific incident when apparently 38 bystanders observed a woman being murdered and did nothing to help.61 Latane and Darley (1968) introduced the notion of the “bystander effect,” which postulates that the more bystanders there are at an emergency event such as this, the less likely it is that anyone would intervene, due to diffusion of responsibility, see also Darley and Latané (1968). However, other researchers have also suggested the importance of social identity as a factor, the perceived relationships between the people involved, for example, see Reicher et al. (2006); Hopkins et al. (2007); Manning et al. (2007); and Levine and Crowther (2008). There is a meta-analysis and review of the field by Fischer et al. (2011). As pointed out by Rovira et al. (2009), one of the problems in this area of research is that for ethical and practical reasons it is not possible to actually carry out controlled experimental studies that depict a violent incident such as that described in the opening paragraph of this section. This is very similar to the situation of the Obedience studies discussed above. Instead, researchers have to study surrogates such as the responses of people to someone falling (Latane and Rodin, 1969) or responses to an injured person laying on the ground (Levine et al., 2005). However, these are not violent emergencies so that it may not be valid to extrapolate results from such scenarios to what might happen in actual violent emergencies. In VR it is possible to set up simulated situations, where we know from presence research that people are likely to react realistically to the events portrayed. King et al. (2008) suggested the use of Second Life to provide a non-immersive simulation of the bystander situation and described a case study where a particular person was victimized to examine how the presence of bystanders mediated the level of helping offered. It was concluded that one reason that people did not intervene was that they thought that this should be the responsibility of the Second Life monitors rather than the ordinary “citizens.” In another video-game setting, Kozlov and Johansen (2010) found that participants were less prone to helping behavior in the presence of larger groups of virtual characters. A possible problem though with using video games is that they do not mobilize the body – there are no natural sensorimotor contingencies so that PI becomes something at best imaginal. In some applications this may not be important. However, when studying people’s responses to emergency situations it may be prudent to have whole body engagement, some illusion that the body itself is present and at risk. Garcia et al. (2002) showed that only imagining the presence of other bystanders results in a bystander effect to the extent that participants are less likely to help others after the end of the study if they had been primed to think about or being in a group than being alone. Hence, it might be the case that video games are mainly aids to imagination and that results obtained from video games might be the same as those from imagination. Indeed, a result from Stenico and Greitemeyer (2014) suggests that this might be the case. This is not to say that such results are invalid but that by themselves they are not convincing enough, and some experimental evidence is needed that does place participants into the midst of a violent emergency so that various factors influencing their responses can be investigated. But, as we have said this cannot be done both for practical and above all ethical reasons. Slater et al. (2013) used immersive VR (a Cave-like system) to study the social identity hypothesis: that participants who share social identity with the victim are more likely to intervene to help than if they do not share social identity. The method to foster social identity with a virtual human character was through the use of soccer club affiliation. All of the n = 40 participants were fans of the English soccer team Arsenal. They were in a virtual bar where they had an initial conversation with a life-sized male virtual character (V). This character was either an Arsenal supporter depicted through his shirt and his enthusiastic conversation about Arsenal (n = 20, “ingroup” condition), or a generic football fan, not a supporter of Arsenal (n = 20, “outgroup” condition). After a while of this conversation another character (P) – also wearing a generic soccer shirt but not Arsenal – butted in and started to attack V especially because of his support of Arsenal. This attack increased in ferocity until after about 2 min it became a physically violent attack.62 The main response variable was the number of times that the participant intervened on the side of V. It was found in accordance with social identity theory that those in the group where V was an enthusiastic Arsenal supporter intervened much more than those in the other group. There was a second factor, which was whether or not V occasionally looked toward the participant during the confrontation, but this had no effect. However, there was a positive correlation between the number of interventions and the extent to which participants believed that V was looking toward them for help – but only in the ingroup condition. Since it is impossible to compare these results with any study in real life, of course their validity in the sense of how much they would generalize to real-life behavior cannot be known. However, experiments such as these generate data and concomitant theory, which can be compared in a predictive manner with what happens in real-life events. In fact, there is no other way to do this other than the use of actors – which as mentioned earlier can run into ethical and practical problems. Moreover, the knowledge gained from such experiments can be used also in the policy field, for example, providing advice to victims on how to maximize the chance that other people might intervene to help them, or of use to the emergency or security services on how to defuse such a situation.63 It is a way to provide evidence-based policy, and if the evidence is not generalizable to real situations then with proper monitoring, the policy will ultimately be changed. “In today’s interconnected world, culture’s power to transform societies is clear. Its diverse manifestations – from our cherished historic monuments and museums to traditional practices and contemporary art forms – enrich our everyday lives in countless ways. Heritage constitutes a source of identity and cohesion for communities disrupted by bewildering change and economic instability.” (Protecting Our Heritage and Fostering Creativity, UNESCO).64 The preservation of the cultural heritage of a society is considered as a fundamental human right, and there is a Hague Convention on the protection of cultural property in the event of armed conflict.65 As we have seen tragically in recent years, there has been massive and deliberate destruction of cultural heritage, two well-known examples being the Buddhas of Bamiyan66 and the partial destruction of Palmyra.67 UNESCO maintains a country-by-country world heritage list.68 The ideal way to preserve cultural heritage is physical protection, preservation, and restoration of the sites. There has also been significant work over many years concerned with digital capture and visualization of such sites, which of course can be displayed in VR (Ch’ng, 2009; Rua and Alvito, 2011). The first and obvious application of VR in this field is to allow people all over the world to virtually visit such sites and interactively explore them. This is no different from virtual travel or tourism, except for the nature of the sight visited. This is also possible through museums that have VR installations. The second is digitization of sites for future generations, and especially those that are in danger of destruction either through factors such as environment change or conflict. The third type of application is to show how these sites might have looked fully restored in the past and under different conditions such as lighting conditions. For example, it is quite different to see the interior of a building or a cave with electric lighting than under the original conditions that the inhabitants of that time would have seen them – by candlelight or fire. The fourth is to see how sites, both cultural heritage and non-cultural heritage sites might look in the future, under different conditions such as under different global warming scenarios. This is a massive field and mainly concerned with digitization, computer vision, reconstruction, and computer graphics techniques. Here, we give a few examples of some of the virtual constructions that have been done and that potentially could be experienced immersively in VR. An example of one type of application is described by Gaitatzes et al. (2001) who show how museum visitors can walk through various ancient sites visualized in a Cave-like system, in particular through the ancient Greek city of Miletus.69 Carrozzino and Bergamasco (2010) give various examples of museum installations.70,71 Interestingly, they speculate on a number of reasons why the use of VR in museum settings may not have been taken up so much recent years: (1) cost; (2) it requires a team to be able to do this; (3) lots of space is needed for the installation; (4) visitors do not want to wear VR equipment; (5) it is a single person experience; and (6) VR might be thought to be not serious enough to include in such august settings as museums. Apart possibly from the last issue, each of these problems is largely overcome with the advent of low-cost, high-quality HMDs with built-in head tracking. Of course it is still true that an interdisciplinary team is required to create the environments, although see Wojciechowski et al. (2004) and Dunn et al. (2012) for an example of how to do this. In particular, digital acquisition and rendering of cultural heritage sites requires a huge amount of data to be processed. An example of how this was handled for the site of the Monastery of Santa Maria de Ripoll in Catalonia, Spain, is presented in Besora et al. (2008) and Callieri et al. (2011) and an example of a user interface for virtually navigating this site in Andújar et al. (2012). A famous example of the virtual recreation of world heritage is the digitization and rendering of Michelangelo’s statue of David plus several statues and other artifacts of ancient Rome (Levoy et al., 2000). The David statue72 required 2 billion polygons for its representation, and the software is available as freeware from Stanford.73 Sometimes a digital reconstruction is the only way to view a site. The ancient Egyptian temple of Kalabsha was physically moved in its location to preserve it from rising flood waters. Sundstedt et al. (2004) digitally reconstructed it to show it in its original site, and also how it may have looked two millennia earlier, including illuminating it with simulations of the type lighting that may have been used at that time. Gutierrez et al. (2008) describe a method for highly accurate illumination methods for heritage sites. Happa et al. (2010) review various examples of illuminating the past, together with descriptions of the methodology used. Many examples of virtual cultural heritage in the past have been implemented for desktop or projection systems – though of course they could always be displayed immersively in HMDs. However, this raises other issues such as appropriate tracking, interfaces, and so on. A joystick for navigation, for example, is not always appropriate for an HMD (especially bearing in mind that movement without body action can sometimes be a cause of simulator sickness). Also a screen display has the advantage that typically it can be much higher resolution than what is possible in an HMD, where all the detailed lighting and detail rendering might not even be perceivable. Webel et al. (2013) describe their experience with a number of the newer technologies for display and tracking in the virtual construction of four different sites for display in a museum. They point out how traditional systems, such as tracking, requiring the wearing of devices, and expensive Caves are not always suitable for busy environments such as museums. However, low–cost, camera-based tracking systems do not require physical contact with visitors, and the use of the Oculus Rift HMD (in their application) allowed visitors to look around the virtual environment simply by turning their head rather than learning a joystick type of navigation method. In other words, these systems provide a natural means of interaction. As the authors wrote: “With the Oculus Rift as a display and head-tracking device, the user’s immersion can be extremely increased. The natural camera control just by turning the head, like one would do in the real world, lets users control this aspect without even thinking about it. The combination with natural interaction inputs with the Kinect or the Leap Motion enables the user to directly interact with the virtual world.” Kateros et al. (2015) review the use of Oculus HMDs for cultural heritage and show how they were used in a number of applications and give insight into their ideas for preparing a user study. Casu et al. (2015) carried out such a study comparing the viewing of art masterpieces in the classroom through a non-immersive multimedia white board display and the Oculus Rift. Their experiment had n = 23 students in a between-groups design (12 saw the non-immersive display) and found that the HMD method was superior across a range of subjective questionnaire-based factors including motivation. Such studies, while useful, do not address the problem of the “wow factor,” i.e., using the HMD is novel, and it certainly provides a quite different experience than the multimedia white board. However, maybe once such systems become commonplace, the same results might not be obtained. There are no clear-cut answers, and it is not easy to establish criteria for the success or otherwise in comparing such systems (since there are many factors that vary between them). For example, Loizides et al. (2014) compared a powerwall with an Oculus Rift HMD for virtual visits to cultural heritage scenarios in Cyprus. They found that participants appreciated both types of display and especially the presence-inducing capabilities of the HMD. However, the HMD also led to greater nausea. As mentioned though, it is very difficult to make such comparisons because on the one hand the HMD had the natural interface for viewing (head tracking) but on the other hand much lower resolution. Moreover, the price ratio between powerwall and HMD was (at that time) 40 to 1, a factor not reflected in the difference in participant evaluation. Finally, it should be noted that cultural heritage is not only buildings and statues. There are rich traditions in societies that are passed down the generations that are certainly no less important to preserve for the future – intangible heritage. An obvious example is folklore stories, but the medium for the ultimate representation of these for preservation through the generations is in written form. However, there are other examples, such as folk dances – which can be preserved through younger generations learning these from their elders – but this does not provide a form for others to experience. Aristidou et al. (2014) show how folk dancing can be digitally captured and represented.74 They concentrate on the technical aspects, but clearly such efforts can be portrayed immersively (see Presentation S3 in Supplementary Material). Sometimes in our professional and personal lives we are faced with problems that cannot be answered by any kind of evidence-based scientific reasoning. The science can provide information, but it cannot determine what should be done. Imagine that there is a nuclear reactor providing power for millions of people, and that the science determines that in the next 10 years there is a 5% chance that it will explode causing massive contamination. There are no resources to repair it and no alternatives. It can be decommissioned, and in the short to medium term this will cost many lives and great suffering. It can be left to run, with the corresponding risk. The science can determine the level of risk, but it cannot determine the action. In military or police action, there is the issue of “collateral damage.” Action to resolve one kind of threat that might save many lives may indeed cost many lives in its execution. The science can inform about relative risks and costs, but it cannot determine what is the right thing to do. How people “should” and do make decisions under such conditions of moral uncertainty are subjects for study in moral philosophy and neuroscience. Normally, abstract situations are used for reasoning or gathering evidence about the responses of people. A famous example is the “trolley problem,”75 where you have to make a choice between allowing a runaway trolley (or tram or train…) to run over and kill five unaware people in its path or diverting it to kill another person (Foot, 1967; Thomson, 1976). What do you do? Suppose the trolley were running toward the one person, but there were five others on another track. Would you divert to the train to save the one but kill the five? According to survey evidence (Hauser et al., 2007), most people will choose the action that saves the greatest number – five rather than one.76 Suppose to save the five, however, you have to push someone else onto the track to divert the train. In this case, few people will choose to take that action. Philosophers distinguish between utilitarian and deontological principles. The first states that it is best to take the action that maximizes the greatest good, i.e., is concerned with consequences (the end justifies the means). The second emphasizes rather that an action in itself must be ethical, based on universal maxims. For example, if it is wrong to steal then it is wrong to steal in any circumstances, irrespective of possible beneficial outcomes. See Hauser (2006) for an exposition of these various principles in the context of psychology and neuroscience. Although sacrificing one person to save five is the utilitarian solution, people also do act out of deontological principles – which is why few support actively pushing someone onto the track even though the outcome is exactly the same in utilitarian terms. Moreover, choosing to take the action of diverting the train to save five rather than one has the same outcome as not choosing to divert the train when it is running toward one with five on another track (omission). However, omission could be argued to be both utilitarian (five are saved rather than one) and deontological (not personally taking an action that would kill). These discussions have been going on for centuries. But, how can we know what people would actually do? As we saw in the example of the Stanley Milgram Obedience experiments (Section 4.3) what people might say they would do and what they do actually do when faced with a situation are not necessarily the same. Below we give some examples where VR has been used, relying on its presence-inducing capabilities, to face people with such dilemmas and where their behavior can be observed. Of course, this does not solve the moral problem of what the “right” behavior should be, but rather can inform about what people actually do, and ultimately the factors and brain activity behind this. Transforming a short verbal description of a scenario such as the trolley problem into VR is non-trivial. There are “five people” – which people? Gender? Age? Ethnicity? Social class? How do they look? What are they doing? Why are they there? There is a trolley or train – exactly how does it look? How fast is it going? What is the surrounding scenery? The experimental subject can divert the train – exactly how? Which action needs to be taken? How can the designer be sure that the subject will even be looking in the necessary direction? How can it be set up so that the subject sees the five and also sees the one? Doing something in VR means making it concrete and specific, obviously changing the scenario – which in one case is dependent on the imagination of the subject in response to a statement in a questionnaire, but in the other is there to be seen and heard. Navarrete et al. (2012) implemented a version of the trolley problem, making all of the above choices but staying true to the story line, and they carried out an experiment where participants were faced with the choice between saving five or one.77 There were n = 293 participants who experienced the scenario in an HMD-based system (NVIS). This was a between-groups experiment where one group experienced the action condition (they could act to save five) and the other group the omission condition (if they did not act five would be saved). Just over 90% of subjects chose the utilitarian solution in line with questionnaire-based results. However, those who had to actively save the five showed greater arousal (skin conductance levels) than those who could save the five by doing nothing. Moreover, the greater level of arousal was associated with a lower propensity to take the utilitarian outcome. This could indicate that following the utilitarian path leads to greater internal conflict within participants, but following it without simultaneously violating deontological principles is a less stressful choice. Ideally, in order to rule out the effect on arousal simply of carrying out the action there should be a condition that equalizes the level of physical action across the conditions. However, the important point is that such studies can be carried out at all. Pan and Slater (2011) portrayed a dilemma equivalent to the trolley problem. Participants were taught how to control a platform that operated as an elevator in an art gallery. The gallery consisted of two floors, ground and upper level. Virtual characters entered and could ask to be taken to the upper level to view the paintings there or remained on the ground floor. At one point – in the Action condition – there were five characters on the upper level and one on the ground level. A seventh person entered and asked to be taken to the upper level. While still on the elevator, that character raised a gun and started to shoot toward all those on the upper level. The participant could leave the shooter there (risking the five) or bring the elevator down (risking the one). The Omission condition was similar except that at the critical moment there was one character upstairs and five downstairs. To avoid the problem that the types of people represented by the virtual visitors might influence the results they were portrayed as stick figures, so that characteristics such as those mentioned above – age, gender, etc. – could not be inferred. This was a between-groups experiment with 36 participants in 2 factors: the situation was portrayed in a 4-screen Cave-like system or on a single PC screen. The second factor was the Action and Omission conditions. Running such an experiment in VR really illustrates how different it is than telling people a story and asking for their response. For those in the Cave their fundamental reaction was confusion or panic illustrated by the fact that 61% of them carried out multiple actions in response to the shooting compared to 33% of those in the desktop condition. However, taking into account the final resting point of the platform, 89% of those in the Action condition in the Cave brought the lift down, whereas 22% did so in the Omission condition. For those in the desktop condition the equivalent proportions are 67 and 22%. The differences between Cave and desktop were not significant, although being a pilot experiment the sample sizes were small. This experiment was featured in a BBC Horizon documentary “Are You Born Good or Evil?” where people naïve to the experiment were filmed. More than the statistics, their reactions pointed to the fact that they did actually experience a genuine dilemma.78,79 A more sophisticated version of this setup was repeated in an HMD-based study (Friedman et al., 2014) concerned with embodiment and time travel, where realistic virtual characters were portrayed. In terms of responses to the dilemma they were similar to the other studies. In these studies it has been found that people become more utilitarian in VR compared to what they will say in response to a questionnaire – i.e., they are more likely to adopt a decision depending on the outcome (saving five rather than one). In another study that used desktop VR the same was found. Specifically, subjects were more likely to make utilitarian decisions in VR compared to the same scenario described textually. In other words, although participants judged it less acceptable to sacrifice one person to save five when this dilemma was presented verbally, when it came to their actual action in VR they were more likely to do so. There is therefore a division between what people will say they would do and what they would actually do faced with the situation. This illustrates what VR is useful for in these types of context. Finally, Skulmowski et al. (2014) used a screen-based system to situate participants in a trolley that they could control and avoid colliding with people standing on branching tracks. They investigated a number of hypotheses relating to specific types of potential victims (male, female), the number balanced against each other (e.g., 10 people rather than 5 against 1, or 1 against 1), ethnicity, altogether with 11 different hypotheses. They found that there were different response times depending on gender of the potential virtual victims, with a greater tendency to sacrifice males. In this study, arousal was estimated by measuring pupil dilation (see Presentation S4 in Supplementary Material). One area in which VR is likely to flourish in the coming years, as its cost comes down and it becomes more ubiquitous, is for the training of professionals. In many professions, people make fundamental ethical decisions – not so dramatic as the trolley problem, but nevertheless often very important. How does a lawyer act knowing for certain that a client has committed a horrific crime? Does a health inspector close down a factory putting at risk hundreds of jobs or allow the factory to continue with unsanitary practices – when it is clear after several warnings that there will be no significant improvement? With limited resources should an agency responsible for deciding which medicinal drugs should be available on prescription go for the cheaper one that has been shown to have limited success, or the vastly superior one that is also vastly more expensive? Choosing the latter might disadvantage the greater number of people due to restrictions on other drugs, yet also save the lives of a few. Sometimes, these issues are covered by law and sometimes not. We consider one example. How do medical professionals learn to interact with their patients in such circumstances? Of course they observe their supervisors and teachers, and they read and learn about this in medical school. However, there is no substitute for experience. But, experience requires that prior to interacting with patients the doctors have already learned to interact with patients. Hence, VR can provide training and many different scenarios that will help toward gaining experience (Cook et al., 2010). The idea of using virtual patients has been very thoroughly studied for many years80 (Cendan and Lok, 2012). For example Kleinsmith et al. (2015) has investigated empathy training with virtual patients. Here, though we consider only ethical problems in dealing with patients – where contrary to medical advice a patient demands a certain medicine; the first time that a doctor confronts this problem with a patient would typically be with a real patient. A case in point is the overprescription of antibiotics. This is a balance between the needs of society as a whole (to avoid enhanced bacterial resistance to antibiotics) and the needs of the individual. If a patient demands antibiotics but the medical evidence suggests that these would not be appropriate, does the doctor prescribe in order to have a quieter life, or perhaps avoid being sued should the decision ultimately have been a wrong one, or follow the higher principle that not prescribing unless clearly necessary may be the best thing to do for the greater good? Pan et al. (2016) carried out an experiment with n = 21 medical doctors (general practitioners; 9 being trainees with limited experience and the remainder with an average of about 6 years’ experience). The experiment was carried out using an Oculus DK2 through which each doctor had a consultation with a virtual mother and her daughter. The mother had a small cough, and the daughter demanded that the mother be given antibiotics because when faced with the same problem a year before, the antibiotics had cured the problem immediately. Since the medical indications were that this was probably a viral infection, the participants (GPs) resisted the demand for antibiotics, which unleashed a torrent of complaints and anger from the virtual daughter.81 Finally 8 out of the 9 trainees prescribed the antibiotics, whereas 7 out of the 12 experienced doctors did so. The results also suggested that for those in experienced group, the greater their reported level of presence the less the probability that they would administer the antibiotic. The use of this type and many other scenarios in the medical and other professions could be of great utility in training, and preparing people for situations that they are almost bound to face eventually. Just as airline pilots first learn on simulators so the same is likely to be true across a range of professions. Using VR, it is possible that you may not need to have physically gone to a place to say that you have visited it. Sitting in your home you can be navigating the streets and shopping in Hong Kong, ascending Mount Everest, visiting the Taj Mahal, exploring the Forbidden City in Beijing, or even the landscape of Mars. You can watch at first hand ceremonies and customs from Polynesia to Greenland.82 This is an obvious and long-discussed application. There are various possibilities: to visit a place virtually before going there, to visit the place instead of going there, to have a business meeting virtually with remote partners, meeting in a shared virtual environment, have a break on a beach in the middle of the day in winter during your coffee break in the office; the possibilities are limited only by imagination and what technology can deliver at the time (which of course is always changing). This is far from a new idea. Already two decades ago people in the travel industry were considering the “virtual threat to travel and tourism” (Cheong, 1995), arguing that “the perceived threat of virtual reality becoming a substitute for travel is not unfounded and should not be ignored. Virtual reality offers numerous distinct advantages over the actual visitation of a tourist site … that could result in the eventual replacement of travel and tourism by virtual reality.” The advantages of VR suggested were (1) technology could eventually support “the perfect virtual experience” where the sun never stops shining (for one kind of holiday), or the snow is perfect (for another kind), there are no unruly (real) people around, and so on. (2) It is convenient – there is not the stress of traveling, it is significantly cheaper, there are no inconveniences. (3) Places could be visited that are not easily accessible (Mars is an extreme example). One could even travel in the past or to fantasy worlds. (4) People who are unable to travel because of illness or disability would easily be able to do so. (5) There are no risks – tropical diseases, accidents, and food poisoning. (6) There is no damage to the places visited. (7) Business travel could be simplified. However, Cheong (1995) goes on to discuss the reasons why this might not really be a threat – virtual immersion is not the same as really being there; it would be difficult in VR to engage in exchanges with the locals (like discussions in a market, learning to dance the Hula); there is a level of complexity and randomness in the real world that cannot be reproduced in VR; people might confuse reality and VR; and there would be problems with countries whose revenues depend greatly on tourism. On the one hand, of course since 1995 tourism has not been replaced by VR (on the contrary – see the next section), but on the other hand, none of the objections above seem insurmountable (even revenue from tourism could be protected by some kind of royalty system). Moreover, as global warming becomes an increasingly serious prospect and threat, VR could provide a way of lessening some of the negative impact of travel. An article by Guttentag (2010) suggested that VR could be useful for tourism for planning, management, marketing, entertainment, education, providing accessibility to inaccessible places such as archeological sites (see Section 4.5) with consequent heritage preservation. However, Guttentag wondered whether VR could ever provide an alternative to real travel, emphasizing a point made in Cheong (1995) that VR may never be able to substitute basic sensory experiences – “the smell of ocean spray” or make virtual surfing feel like the real thing. In other words, at the end of the day will VR ever be technically up to the mark in providing a genuine substitute for the real experience? In this section, we do not attempt to answer this question, since the answer cannot be known. Rather, we describe what has already been accomplished in this realm across a variety of applications that require some kind of travel. Perhaps, VR is not meant to be a substitute for real travel but just another form of travel, no less valid in its own terms than all that physically boarding the real aeroplane entails. The contribution of travel to the world economy is colossal. According to the World Travel and Tourism Council (WTTC, 2015), travel and tourism generated $7.6 trillion in 2014, amounting to 10% of global GDP. It also accounted for 10% of all jobs (277 million), with the travel economy growing faster than other sectors such as health, financial services, and automotive. See also the extensive statistics produced by the World Tourism Organization UNWTO.83 On the other side, travel comes with significant costs (Reford and Leston, 2011). The first obvious one is the potentially disastrous impact on the planet’s environment (Zhou and Levy, 2007) including the negative impact on health of air pollutants – e.g., Curtis et al. (2006) and Kampa and Castanas (2008) – see, for example, a meta-analysis by Mustafić et al. (2012) that reports a clear relationship between many of the associated pollutants and the near-term risk of heart disease. A second problem is especially in regard to business travel. In the US alone, $283B was spent on business travel in 2014.84 However, such travel can be disruptive both to the business and the personal life of the traveler (Gustafson, 2012) including contributing to family conflict and burnout (Jensen, 2014). Nevertheless, for business (let alone personal and family relationships) face-to-face contact is thought to be essential. Even if face-to-face meetings can be substituted by one of the various forms of teleconferencing systems available, it has been suggested that these types of virtual meetings may even generate greater physical travel (Gustafson, 2012). In an analysis of the relationship between air travel and the possibilities offered by videoconferencing in the past four decades Denstadli et al. (2013) did not find any clear picture and certainly not the case that videoconferencing might substitute air travel. Based on the analysis by Jones (2007), it is argued that face-to-face meetings are important for completing projects across international sites, maintaining commitment to strategic plans and shared organizational culture, knowledge sharing, creativity, and new services. There are of course related issues such as trust, using business meetings to get away from the office from time to time, taking the opportunity to meet friends or relatives in remote locations, and so on. Hence, face-to-face meetings seem to be essential, and interestingly it is precisely those who travel the most who engage in most videoconferencing meetings. Hence, there is a complex relationship between the two. Nevertheless, in the study of Denstadli et al. (2013) (n = 1413), of those who had access to videoconferencing tools one-third said that they believed that some air travel could be replaced by videoconferencing. For example, probably some readers of this article would have experienced the situation of several hours of travel to attend or speak at a 1-h meeting and then to travel home shortly afterward – sometimes wondering what the point of it all might have been. Can VR be of benefit in this domain? In this section, we briefly review the possibilities offered by immersive VR as a means for enabling remote communication and collaboration. We consider a virtual environment that is shared between multiple participants. Each participant is represented by a virtual body (an “avatar”) and can see the representations of the others. Ideally participants’ movements are tracked, they can move through the virtual environment, and can talk to one another. Hence, they are in a 3D stereo surrounding space along with others. Of course, there are several technical issues involved in how to realize such a system (Steed and Oliveira, 2009), such as how and where to distribute the computation (one master machine broadcasting to all the others or a distributed network?), how to keep the various participant environments synchronized with one another so that they are all able to perceive the same consistent environment etc., but these issues are not considered here. In its ideal form, such a system must be superior to videoconferencing – since for example, the latter cannot display spatial relationships, eye contact, and so on. However, an ideal form of a shared VR would require real-time full facial capture, eye tracking, real-time rendering of subtle emotional changes such as blushing and sweating, subtle facial muscle movements such as almost imperceptible eyebrow raising, the possibility of physical contact such as the ability to shake hands, or embrace, or even push, and so on. Such a system does not exist today, though it is one to strive for. Some of these capabilities might be realized with the type of VR referred to as 360° surround, but we defer the discussion of this to Section 7.2. In the following section, we review some of what has been achieved and what the likely prospects are. Probably, the first published work where more than one person could simultaneously inhabit the same virtual environment was presented by Blanchard et al. (1990). This was the VPL system that allowed two people each with their own HMD (Eye Phone) and data glove to be simultaneously copresent in a virtual environment. Over the next few years, there were many systems that provided this and typically extending to multiple participants rather than two (Greenhalgh and Benford, 1995; Frécon and Stenius, 1998; Frecon et al., 2001), and today it is a matter of course that VR systems support this capability (Bierbaum et al., 2001; Tecchia et al., 2010), and VR development platforms of recent choice such as Unreal Engine or Unity3D are also multi-participant systems. So, the capability for virtual environments shared by multiple participants has been around for a long time, supported by many platforms, and realized in massive online systems such as Second Life, although typically non-immersively. The work by Apostolellis and Bowman (2014) is a good recent illustration of collaboration in a learning context that was realized with screen-based displays. The early days of research in this area, apart from the technical issues of how to build systems, concentrated on exploiting the capabilities of VR to improve remote collaboration beyond what might be possible even in face-to-face communications – for example, the type of work reported in Benford and Fahlén (1993) and Koleva et al. (2001). However, the primitive representations of people (very crude block-like characters) due to the relatively limited graphics and processing power at the time made this of interest only in a research context. Later work concentrated on exploring social dynamics within shared virtual environments. For example, the research described in Tromp et al. (1998); Steed et al. (1999); Sadagic and Slater (2000) and Slater et al. (2000) had three-person groups carry out a task together although they were physically in different places (including even different countries). This also compared the group dynamics in VR to real encounters and found that the dynamics was greatly influenced by the computational power and type of immersion. For example, the group leader that would emerge in VR was the one with an HMD rather than those interacting with the others on screen, but this same person was less likely to be the leader when the group met for real. Also, people were quite respectful of each others’ avatars, notwithstanding their extreme simplicity – for example, avoiding collisions and apologizing when collisions invariably happened. Steed et al. (2003) carried this further by having pairs of people, one in London, UK, and the other in Gothenburg, Sweden, each in a Cave-like system spend around 3.5 h working together. Some of the pairs were friends, and some were strangers. They found that the partners could collaborate well on spatial tasks, where the avatars representing their whole bodies played an important role. However, on other negotiation tasks, where facial expression would be quite important to gage the intentions of the other, the friends did better together than the strangers. A review of this type of avatar-mediated communications can be found in Schroeder (2011). Although during the 2000s the graphics power to display more realistic human avatars in real time and in large numbers became available, the type of “ideal” system mentioned earlier still was far from possible. Nevertheless, researchers began to address critical aspects of non-verbal communications that can make remote face-to-face interactions in virtual environments effective, such as shaking hands (Giannopoulos et al., 2011; Wang et al., 2011). Steptoe et al. (2008) introduced eye tracking as a way to determine the gaze of each individual avatar in virtual meetings between three remote participants (one in London, one in Salford, and the other in Reading, UK) each in a Cave-like system. Analysis suggested that participants automatically used gaze direction much as they would in a similar conversation in reality. This was followed up by Steptoe et al. (2010) who showed that eye tracking data that allowed avatars to be rendered showing gaze direction, blinking, and pupil size resulted in participants being able to better detect one another telling lies compared to a video conferencing system. This was between two participants in different physical places one using a Cave-like system and the other a power wall. Another recent idea for remote collaborative working is for each party to use a whiteboard, where they would see a silhouette of the remote person, like a shadow, on the white board. It was found that participants tended to act as if they were in the presence of the remote person (Pizarro et al., 2015). Although a lot of work on such avatar-mediated communication during this period took place using projection systems such as Caves, Dodds et al. (2011) used HMDs to embody two remote people in the same environment. They found that body tracking, in particular showing arm gestures, played an important role in bidirectional communication between the partners. When, for example, the gestures of the avatar of one of the partners were replaced by prerecorded animations then the communication was not as successful in task achievement. A combination of HMD and Cave system was used for a case study of remote acting, where two actors rehearsed a short scene using a script from The Maltese Falcon movie85 (Normand et al., 2012a). One actor was in Barcelona wearing a full motion capture suit and a wide field-of-view high-resolution HMD. The other actor was in a Cave in London and had some level of body tracking (arm gestures). The two were in the same virtual environment and could see and hear the avatars representing the other. A director was in a separate room in London. He could see and hear the scenario on screen, and video of the director’s face was streamed in real time to both actors. Therefore, the director could communicate to the actors and tell them where to stand, what to say, how to improve their performance – generally act like a director.86 The professional actor involved in London concluded that such a system could be used for remote acting rehearsal especially for aspects such as blocking concerned with spatial locations and movements of actors, lines of sight, and so on. This work was followed up by Steptoe et al. (2012) who used again an actor in Barcelona in VR who saw a virtual representation of the remote London scenario, and she was represented as a wall screen avatar with a spherical display to represent her head to the actor, and the director was in the Cave. See also Steed et al. (2012) for a description of the technology. Observers from the Royal Academy of Dramatic Art commented on the positive potential uses of such a system for rehearsal and blocking, which are the arrangements and lines-of-sights of actors at the different stages of a play. Of course, again the lack of facial expression shown on the avatars is a drawback in these types of system. Another drawback is the lack of touch – if one participant touches the avatar of another then typically nothing would be felt. Bourdin et al. (2013) set up an application where two remote people wearing an HMD and body-tracking suit interacted with a third person (an experimenter) who was in a Cave, so that all three saw representations of one another in a shared virtual environment. The experimenter had the task of persuading the other two to sing together. As part of the persuasion, she could touch the avatars of the two participants on the shoulder, upon which they could feel a vibration from a small actuator located on their shoulder. Thus touch was used as part of the persuasion.87 Earlier Bailenson et al. (2007) carried out experiments using haptic only virtual environments where they showed that touch helped in the communication of emotions between people, both with respect to recognizing emotions recorded as haptics earlier by others, and with respect to simultaneous communications between remote partners. Their paper also contains a review of the field and a theoretical model. Basdogan et al. (2000) using a haptic only environment carried out a series of experiments, which also found that haptic feedback could impart critical information in remote communications. This work culminated in a “hands across the Atlantic” experiment where remote participants, one in London, UK, and the other in Cambridge, MA, USA, carried out joint tasks together such as lifting an object that they saw on screen and using haptics to help in the communication between them (Kim et al., 2004). Apart from describing the technological issues involved in setting up such a system, the results showed that the haptic feedback improved the sense of copresence, that is, that the remote participants felt that they were together. One obvious way to introduce haptics into remote VR-enabled communication is to actually use physical representations of people in the form of remotely controlled robots. This was envisaged and implemented in the very early days of VR. Fisher et al. (1987) described a telerobotic control system developed at NASA Ames (CA, USA), where the participant wearing a head-tracked HMD and other tracking, audio, and tactile feedback equipment received visual input from the cameras mounted on a remote robot. The robotic body essentially visually substituted the person’s own body, therefore appearing to be colocated somewhat like the discussion of embodiment in Section 2.1.1. Recently, this idea of the symbiosis between a person in VR being represented remotely as a humanoid robot has seen some new applications as a particularly exciting form of remote collaboration where the participants are given physical form in the remote place. Here, the participant uses VR to perceive the remote location in full stereo with head- and body-tracking but is represented as a humanoid robot in the remote location. The humanoid robot moves as a function of the real-time body tracking of the participant, who can speak (through the robot) to local people in the remote location. It is a further and up-to-date realization of what was presented in Fisher et al. (1987) except now for the purposes of remote collaboration. An example was shown in a BBC interview.88 The BBC interviewer in London (Technology Correspondent Rory Cellan-Jones) interviewed a scientist in Barcelona who was fitted with a wide field-of-view head-tracked HMD and a body-tracking suit. She was represented as a humanoid robot that was in the same room as the journalist in London. Her movements captured by the motion capture suit were transmitted across the Internet to the robot and applied to it so that it moved almost synchronously and in correspondence with her. A Skype connection allowed her to speak through the robot, whose mouth opened and closed in sync with her speech. Cameras fitted as the eyes of the robot transmitted video back to the HMD, so that she saw the surrounding London environment in stereo. Since the HMD head tracking data were transmitted and applied to the robot head, she could look around the room in London and converse with the BBC interviewer. The technology used was described in Spanlang et al. (2013). The same technology was used to beam journalist Nonny de la Peña from Los Angeles (CA, USA) to Barcelona. In Los Angeles, she wore the body-tracking suit and HMD. She was represented as the humanoid robot in Barcelona. Embodied as the robot, she conducted a debate between three students on the issue of Catalan independence from Spain and also interviewed a scientist about his research on HIV.89 The idea is reminiscent of “beaming” in Star Trek. Instead of a person being physically decomposed, transmitted to a remote place, and then recomposed there, a person in VR has their movements and speech transmitted to the remote place and applied to a humanoid robot, and sensory data – vision, sound, and touch – is transmitted back from the robot’s sensory apparatus to the person, that is perceived in VR. The locals in the remote place interact with the robot that is embodied by the beamer. The beamer, however, through the VR becomes present in the remote place. This has also been used by journalist Nonny de la Peña to beam from London, UK, to Barcelona to interview neuroscientist Dr. Perla Kaliman about food for the brain.90 This journalism resulted in a news article about the results of the interview itself, rather than about the system used to realize it91 (Kishore et al., 2016). The same kind of beaming setup has been used to create a shared environment between a small animal and a human. Normand et al. (2012b) showed a human participant in VR interacting with a virtual human, which in fact was a tracked rat in a cage 12 km away. Simultaneously, the rat interacted with a rat-sized robot, which in fact was moving determined by the tracked the movements of the remote human. Hence, each interacted with an entity at its own scale (the rat with a small robot, the human with a human-sized avatar), leading to interspecies communication. This type of setup is of value in ethology. In an article on animal geography and related issues, Hodgetts and Lorimer (2015) wrote in reference to this work that “… it is claimed that the human and the rat were able to participate in a purportedly playful meeting of species that seems straight from the pages of science fiction. Such experiments in adjusting scale do little to shift power dynamics in interspecies communication. Nor does the lab maze create anything more than a novel environment for encounter. Yet the prospect of engaging with animal worlds in more embodied, interactive and exploratory ways opens new avenues for developing richer accounts of animal lifeworlds.” The issue of non-verbal communications is critical for face-to-face communications, and as we have mentioned above there are attempts to overcome this problem, for example, using eye tracking to animate the eyes of avatars. Telerobotics enables physical presence and to some extent the conveyance of body language, depending on the extent of body tracking and the capabilities of the robot; however, facial expression remains a problem, even though some robots can do this. Nevertheless, the subtle cues of which we are not consciously even aware in communication are not rendered. One way out of this problem has been explored through the combination of animatronics and “shader lamp” technology. Shader lamps project computer-generated images onto neutral objects so that observers would see the simple object as animated. In particular, an animated human face can be projected onto, for example, a spherical or egg-shaped object, thus making it appear as if the physical object were an animated face. Moreover, the face could be one that is captured by face-tracking or video from a remote person. Lincoln et al. (2009) proposed and implemented shader lamps for the faces of remote people projected onto animatronic puppets. The participant could be far away seeing the real surroundings of the puppet through a VR, and his or her face back-projected onto a shell, so that an observer of the puppet would see video of the real face of the distant person, and be able to interact with that person.92 Some research has suggested that this type of technology, where faces are displayed on physical objects, in this case a spherical display, can improve the aspects of trust in remote communications (Pan et al., 2014) (see Presentation S5 in Supplementary Material). The descriptions above of embodiment in remote robots through which social interaction can take place with distant people are reminiscent of movies such as Avatar (see text footnote 11) and Surrogates.93 The fundamental difference is that whereas in the systems above people move their remote robotic bodies through their own deliberate movement (realized through real-time motion capture), in the vision presented in these movies, the remote representation is moved through a brain interface. The participant only has to think or imagine moving the remote body, and it moves the corresponding cyborg or robot body (in the movies perfectly) just as if they were moving their own real body. To a limited extent, this has been achieved today. For example, Millan et al. (2004) were able to control a mobile robot through non-invasive brain recordings or BCIs. Leeb et al. (2006) described their research with a tetraplegic patient who was able to use a BCI to navigate through a virtual environment presented in a Cave. He triggered his movement entirely by the voluntary production or halting of a specified electrical brain signal (EEG pattern).94 The same motor-imagery paradigm was used for the voluntary control of an arm belonging to the participant’s virtual body (Perez-Marcos et al., 2009), resulting in an illusion of ownership over the virtual arm. BCI was used in a telepresence application for disabled patients by Tonin et al. (2011), although the patients did not see the remote environment via VR but rather video on a PC display. Nevertheless, this demonstrated the possibility. A survey of the use of BCI in VR and games was presented by Lécuyer et al. (2008). Martens et al. (2012) demonstrated that a number of whole body tasks could be realized by a participant wearing an HMD embodied in a remote robot controlled through various BCI paradigms. Participants could pick and place objects, and engage in a game. This study also illustrated how the BCI could be used to recognize the intentions of the participant (for example, pick up a glass) and the robot would execute and complete the intention (since non-invasive BCI today simply does not permit the fine control necessary). The lack of fine motor control results from the fact that most BCI systems use non-invasive scalp electrodes that therefore record brain signals of low spatial resolution. For patients who cannot otherwise move, acting in the world through the motor control of a robot is a possibility that may justify (invasive) brain implants. Small electrodes placed in the cortical tissue record the activity of groups of neurons with higher spatial resolution, allowing the control of finer movements. Wessberg et al. (2000) first showed that direct recording from the neurons in monkeys enables them to control quite sophisticated movements of a remote robot arm without using their own real arm. A similar approach has been used in people with tetraplegia that could successfully control robotic arms through brain implants (Hochberg et al., 2006, 2012). Moreover, depending on what the actuators may encounter, feedback can be used to stimulate appropriate groups of neurons that cause different tactile sensations. This was realized in monkeys by O’Doherty et al. (2011) where they were able to move a virtual arm that touched virtual objects distinguished only by their texture. Such technology could be used to drive prostheses that replace missing limbs, or exoskeletons that move actual but paralyzed limbs, or virtual bodies experienced in immersive VR or remote physical robots or cyborgs. The latter possibility is the vision of Avatar and Surrogates. In each case, people perceive through the senses of their remotely embodied cyborg or robot and act in the world through those bodies. In John Scalzi’s novel Lock In95 people suffering from “locked in syndrome” are present in the world through such robot embodiment. Although these are works of science fiction they are beginning now to be technically feasible and almost surely are going to be realized with the advance of neuroscience, VR, and robotic technology. For example, Kishore et al. (2014) showed how BCI could be used to embody people in a remote robot through which they could gesture and maintain a conversation with the people there.96,97 The “Embodiment Station” reported by Leonardis et al. (2014) was inspired by the setup in Surrogates. The Embodiment Station is a large chair that is a mobile platform that can induce force feedback (see text footnote 97 from minute 2:50). The participant is fitted with an HMD and has a multitude of physiological responses recorded and various different types of stimulation applied to his or her body. The participant may be embodied in a virtual body or remote physical body. People in Avatar are shut into a tubular structure that monitors their brain and provides feedback so that they become embodied into a remote genetically engineered cyborg body. Cohen et al. (2014b) [see also Cohen et al. (2012)] show how to use real-time fMRI to decode particular thoughts of participants so that they are able to embody a virtual character98 and control a remote robot thousands of kilometers away (Cohen et al., 2014a).99 Although of course the degree of control and the level of embodiment are generations away from what is depicted in Avatar, it is nevertheless a clear step along the road toward this vision (see Presentations S6 and S7 in Supplementary Material). During the 25 years when VR was supposedly dead, or at best confined to University laboratories, industry was busy using it to develop products, inventing new methods of manufacturing, assembly and training, maintenance, and shopping. We briefly review some work in this area. In a major review of the use of VR in car manufacture, Lawson et al. (2016) pointed out that VR can be used for design, avoiding the complex and expensive procedure of building physical mockups. With a mockup, any small change can result in major new work. Of course, VR is far more flexible in this regard. VR is also used for virtual manufacturing, that is part of the preparation, planning, and risk assessment in the manufacturing process, and clearly also invaluable for training. VR can be used for learning the assembly and disassembly of parts. Data from an in-depth survey revealed that VR was being used for a number of aspects in the design, manufacture, and evaluation – to examine the look of the vehicle including product reviews with clients, motion capture of manufacturing procedures, reviews relating to ergonomic use of the vehicle. There has been significant work on industrial assembly, training for maintenance and remote maintenance – for example, Gavish et al. (2011, 2015) and Seth et al. (2011). This is also enhanced by the possibility of mixed reality where a participant in a VR can see their own hands incorporated into the virtual environment (Tecchia et al., 2014; Sportillo et al., 2015).100 Immersive VR is also being used for automobile testing.101 In another context, Tiainen et al. (2014) found that customers were equally at home in evaluating furniture presented virtually as physically. Indeed, they made more suggestions for design improvements in evaluations of the virtual products. Customers designing aspects of the interior of automobiles is also being prototyped using HMD-based VR.102 Virtual reality has also been used in the clothing industry where powerful computer graphics-based cloth simulators are used to allow customers to virtually try on clothes on virtual representations of their own bodies (Hauswiesner et al., 2011; Magnenat-Thalmann et al., 2011; Sun et al., 2015). Although not yet used in an immersive way, such systems are bound eventually to be a normal part of shopping – as we will have our own body representations, trying on clothing in the comfort of our homes without the inconvenience of traveling, queues, and fitting rooms would be a possible major application. A final example is a highly innovative potential application in the food industry. Ruppert (2011) describes how VR is used to study the behavior of shoppers in response to different kinds of packaging and layout in supermarkets. It is suggested that where consumers want to buy healthier products that experimentation with different types of presentation could result in knowledge about how to best present such products so that they stand out for these types of consumer. As argued by Lawson et al. (2016), VR can improve the prototyping, production, evaluation processes in manufacture, it can also be part of the design process, and ultimately for marketing. It also offers the possibility of consumers being involved in design and even designing aspects of the products that they will buy. In fact, VR combined with 3D printing could totally revolutionize how products are designed, manufactured, and delivered, giving enormous new power and possibilities to consumers103 (see Presentations S8 and S9 in Supplementary Material). We have already mentioned the potential benefits of VR for travel, for visiting remote relatives, and so on. Moreover, the use of VR in games is obviously going to be a huge area of application and one of the driving forces of the industry.104,105 There is a clear role also for immersive movies, where the participant plays a role within the story, somewhere between a game and a movie. These are such obvious applications of VR we are not going to discuss them further here. The chances are that any person first learning of VR in 2016 will do so because of a game or movie. In this section, we therefore concentrate on a quite novel field that VR opens up, which is the immersive presentation of news. This is usually called “immersive journalism.” However, it is important to note that it is not the journalism that is immersive but the presentation of its results through immersive media, leading to the creation of a genuine new type of media for news reporting. We will consider the issues involved, including ethical issues, and finally discuss the differences between computer graphics-based VR and 360° video. The idea of immersive journalism is “the production of news in a form in which people can gain first-person experiences of the events or situation described in news stories” (de la Peña et al., 2010). Let’s consider the main headlines (online) of the Los Angeles Times on January 23, 2016 and see what this might mean. If we compare the report with the VR version we can see that they reflect quite different purposes. In each row, the left side is the reporting of “news” (“Newly received or noteworthy information, especially about recent events,” Oxford English Dictionary). There are masses of academic research studies and theories of what makes it into “The News” (as reported by newspapers, radio, TV, and of course now myriad online outlets). Interested readers could read, for example, a classic analysis by Galtung and Ruge (1965) who identify a number of factors that influence what events typically get into the news, and a follow-up study by Harcup and O’Neill (2001) who examined the earlier theory in the light of a content analysis of stories in three British newspapers. The theory includes factors such as those events involving elite nations or persons are more like to be newsworthy than non-elites. For example, news in Western media is more likely to report on events in the USA, Europe, China, and Russia than in the Seychelles, except, for example, when events in other places directly affect those countries (e.g., events in the Middle East). The divorce of a movie star is far more likely to make it into the news than the divorce of your next-door neighbor (unless you happen to live next to a movie star). However, who decides what is important? This reflects another aspect of news, which is that there are not events just “out there” floating around, and they just happen and then are selected by journalists according to some criteria and then reported factually, but it is an active process where what is news is defined by journalists and multifarious interests and ideologies that make up particular media cultures (O’Neill and Harcup, 2008). For example, a President attends an important international event. If the President is a man, the reporting may focus on the event and its background. If the President is a woman, a great deal of attention may be instead paid to her clothing.106,107 News values can differ enormously between different organizations. What makes it into the equivalent of the left side of each row in the table above, and how it is reported, are not simply matters of fact. Now considering the possible immersive VR versions there is quite a difference – the goal is not so much the presentation of “what happened” but to give people experiential, non-analytic insight into the events, to give them the illusion of being present in them. That presence may lead to another understanding of the events, perhaps an understanding that cannot be well expressed verbally or even in pictures. It reflects the fundamental capability of what you can experience in VR – to be there and to experience a situation from different perspectives. This is no more or less “objective” than news in traditional forms – what is selected, and how it is presented inevitably will reflect the interests, culture, political views of the journalists involved, and perhaps even more importantly their news organizations. There is no way around that, since what might be “news” is infinite, and something has to be selected. Moreover, how news in VR will be understood will also be actively shaped by the participant. Recall that in VR there are neither “users” nor “observers” but participants or consumer-participants. Even if you are just an observer without the actual ability to intervene, presence in VR is such that you will likely have the perception that ongoing events could affect you. Hence, the consumer of a news story in one medium becomes a participant in the virtual story in the other, the “immersive journalism” that creates a scenario to represent aspects of the news story in VR. However, there is a difference. Let’s go back to the woman President attending an event. A VR rendition of this puts you in the scene in the 1PP of someone who attended and who was greeted by the President. She moves over to you, smiles, and says some words of greeting: to you. Assuming that the journalist had made every effort in visual reconstruction to be faithful to the original event, whether the clothes that the President is wearing stand out or not depend wholly on you, the perceiver. You may pay attention to them or not, you may see them as remarkable or not. If the journalist wanted to really point out to participants the clothing worn by the President, this is of course entirely possible in VR – whether openly or surreptitiously. However, if the goal is to try to be objective, then how certain aspects of the events are interpreted will depend more on the perceiver than on the designer. We will come back to some of these points later. The first immersive journalism piece was developed in 2010 in Barcelona, Spain, and directed by journalist Nonny de la Peña with the help of digital artist Peggy Weil. It followed on from the idea of their 2009 interactive Second Life piece that portrayed a virtual Guantánamo Bay prison.108 The immersive news story was displayed in a Wide5 HMD by Fakespace for the display (see text footnote 18) and incorporated body tracking. It established a pattern that was to be used by Nonny de la Peña in later productions, which was to use a mix of data from actual events combined with a computer graphics-based reconstruction. It relied on transcripts of the interrogation of Detainee 063, Mohammed Al Qahtani, at Guantánamo Bay Prison 2002–2003. The scenario was in a single cell-like room, and the participant was embodied in a virtual character wearing an orange “jump-suit.” From a 1PP, the participant’s virtual body posture was shown in a stress position – one reportedly used for “harsh interrogations.” The participant could see the virtual body either directly looking toward his own body and in a virtual mirror. However, in fact the participant was seated comfortably in a chair. The participant would hear an interrogation as if coming from a cell next door.109 A case study (de la Peña et al., 2010) with three participants was carried out who were interviewed after their experience. All reported that even though they were seated comfortably, they felt uncomfortable, even pain, from the posture of their virtual body. This result that the posture of the virtual body can actually influence feelings of comfort or discomfort of participants has recently found new evidence (Bergström et al., 2016) (see text footnote 54). The three participants felt a foreboding that the interrogation in the next cell would soon shift to them. Although the participants had not been given any forewarning of the meaning of the event that they were to experience, one of them said: “During the experience I was kind of reminded of the news that I heard about the Guantánamo prisoners and how they feel and I really felt like if I were a prisoner in Iraq or some… war place and I was being interrogated.” It illustrates the difference between the left column (traditional reporting of news) and right column (news in VR) in the Table above. The left column might be a written piece about harsh interrogation methods, or a TV news piece illustrating aspects of this. But, on the right hand side there is experience. Of course, this is not the real experience, but may give participants insight into how some aspects of the situations depicted might have been. “Hunger in Los Angeles”110 was a subsequent piece by Nonny de la Peña. This puts participants in a food line in Los Angeles where one of the people in the queue faints due to diabetes, and the various characters around react. It was based on an actual event and blended real sound recordings with computer graphics. The virtual characters in the food line were animated through the motion capture of actors. It was experienced by hundreds of people at the Sundance Film Festival in 2012. The 2014 World Economic Forum featured “Project Syria” by de la Peña, which depicted a bomb explosion in a Syrian town and its aftermath (see text footnote 110). This followed the same pattern of being based on an actual event and starting from video and audio from the real scenario. Further pieces on the same lines are “One Dark Night”111 about the shooting of teenager Travyon Martin and “Kiya” about an incident of domestic violence and murder112 (recall the fifth item in the table above). An alternative to using computer graphics to reconstruct events is the use of 360° video. A scenario is captured by using a special camera and subsequent software to patch video together to form a completely surrounding scene that can be displayed in an HMD. Due to head tracking, the viewer can look all around the scene, and depending on how it has been captured, it can also be displayed in stereo. We will return to the technology in Section 7.2. This is therefore an alternative way of displaying events immersively. “Waves of Grace”113 by Gabo Arora (Senior Advisor and Filmmaker, United Nations) and Chris Milk ( use this technique to recreate the true story of a survivor of Ebola in Liberia. They also created “Clouds over Sidra,” a documentary about a child refugee in the Syrian war.114 Louis Jebb founder and Edward Miller head of visuals of use 360° video to create immersive news events. Some examples have been the coverage of unrest in Hong Kong115 and a 360° VR experience of the paintings of the artist Gretchen Andrew on a self-guided interactive tour of a computer-generated recreation of the De Re Galler in Los Angeles.116 The Des Moines Register working with Dan Pacheco produced a documentary that combined both computer graphics-generated VR and 360°, which can be viewed in an Oculus HMD that provided an in-depth study of the situation of farmers in Iowa, called “Harvest of Change.”117 The New York Times has started VR news based on 360°, using Google Cardboard as the means of display and has created a number of stories with this technology.118 The BBC is also experimenting with 360° HMD-based news,119 for example, providing experience of the refugee crisis.120 At the same time as the great enthusiasm of VR in this domain,121 there are also warnings about its ethics. For example, in an excellent and comprehensive article on potential problems, Tom Kent (Standards Editor, Associated Press and Columbia University) urges “an ethical reality check for virtual reality journalism.”122 The first point concerns the depiction of reality. For example, “Hunger in Los Angeles” was a reconstruction using computer graphics for the display. It was not the real thing. It is important for consumer-participants to always be made aware of this, and it should form part of the ethics code being devised by digital journalists.123 However, it is important to note that all journalistic reporting necessarily involves transformation and cannot possibly ever depict every aspect of reality. At the moment that the news camera focuses on the face of a politician, it of course misses everything else that is happening at the same time, some of which may change the meaning of the facial expression. Depicting any event with its infinite aspects and nuances in any media whatsoever necessarily involves a transformation. As we argued above, starting from what is selected to how it is portrayed involves myriads of choices. VR is no different in this regard. It can be argued that in VR a journalist could, for example, deliberately change the facial expression of a protagonist from a friendly smile (as it was in reality) to an arrogant grin. This could happen deliberately or by accident. However, how different is this from taking a small sentence in a speech of a politician out of context, thus distorting its meaning away from that intended? The use of VR requires ethical standards no more or less than conventional news reporting. Another point relates to 360° video-based pieces, where there is an issue of image integrity. Since the Associated Press does not allow manipulation of images should particularly disturbing parts of a scene on a battlefield or bomb site be left in or not? Again, this is nothing special for VR. Of course a 360° view is less selective than a single camera shot or normal video shot. There are conventions where images are “distorted” though – such as blurring the faces of vulnerable people in order to protect them. It is not clear why such conventions could not be applied in the same way. This is nothing really to do with VR. As we argued in Section 1.1, VR is a media where conventional approaches will eventually be overtaken by a new paradigm. Today, shooting a 3D movie inevitably draws on the conventions of traditional movie making, so that problems of inclusion are paramount, since 360° in principle shows “everything.” New paradigms will eventually overcome this problem. The third point is that there may be competing views of what happened in any event, so VR portraying one version may not reflect the diversity of views. This also has nothing to do with VR. In fact, VR may have an advantage that it is possible to relive a scenario from multiple points of view – from the viewpoints of different protagonists, which may sometimes even explain why they describe an event quite differently. The 1950 Japanese movie “Rashomon”124 received international acclaim for doing this – depicting a story from the multiple points of view of the characters involved. Another version was released in 1964 called “The Outrage.”125 VR could excel in such multi-viewpoint recreations. Tom Kent argues that since VR is excellent for producing empathy, and identification with characters who may be experienced as being physically close to consumer-participants, that journalists have a special responsibility to make sure that their piece is balanced. For example, if they have the goal of producing sympathy toward particular people or situations they could emphasize aspects that provoke empathy or leave out balancing information that could be inconvenient to their story. This is of course true but again it applies no less than to conventional media. It could be argued though that VR is particularly adept at raising emotions and therefore unwitting consumer-participants might be more easily manipulated. This may be true. For example, we have seen in Section 2.1.2 how embodying White people in a Black body appears to reduce their implicit racial bias against Black people (Peck et al., 2013). However, we also saw in Section 4.4 that in a fight between two virtual characters about soccer teams, only participants who supported the same team as the victim tended to try to intervene to stop the fight (Slater et al., 2013). People did not change their behavior simply as a result of being near a virtual character that was attacked by another. In other words, people are not like sponges and just soak up whatever emotion is poured into them. In the racial bias example, participants were generally not explicitly biased, so in reducing their implicit (i.e., largely non-conscious) bias perhaps they were being helped toward realizing their own non-biased preferences. Imagine a VR scenario that placed a United States Democrat supporter into a Republican rally or an English vociferously anti-European voter into the heart of the Brussels decision-making community. Are either of these likely to change their views as a result? Of course, research is needed on this issue, but people should not be considered as empty vessels ready to be filled by whatever propaganda comes along. At the end of the day if a journalist wants to present a particular viewpoint they will do so with whatever means they have, so that the critical requirement is openness, information about potential distortions, and appropriate ethical standards. The final main point made in the article by Tom Kent is that the virtual environment is a circumscribed world, and of course the scenario is embedded in a wider world in which other related events may be happening. On the one side, the VR gives the impression to participants that they can freely go wherever they want, but of course the specific virtual environment has boundaries outside of which nothing can be perceived. This is a problem of selection, applying no less to other news media. When you are reading a story in a newspaper is it the whole story? Of course not, and it never can be. Arguments about the ethics of VR miss the point that it is not the only way or even the “best” way to deliver news (or indeed any story at all, whether supposedly real or fictional). Just as VR is not going to replace novels in the form of books, it is not going to replace traditional media. It is another medium, another method for the production and display of narrative, providing a different kind of “information,” providing a different kind of emotional engagement. These are not “better” or “worse” but just different. You can read about the refugee camp at Calais in France full of people wanting to enter the UK, or you can visit there virtually,126 or really go there. Each of these will provide quite different information and responses. One may give facts and figures and talk about policy and implications for the future of the European Union, another may show the physical and emotional plight of particular people in that camp. Visiting the camp virtually might lead someone already so inclined to do something to try to help the individuals concerned, but not necessarily result in a change in their political convictions about immigration. What is important is that all types of journalism follow ethical standards, and this applies no matter what the medium (see Presentation S10 in Supplementary Material). There is some discussion about whether 360° video as has been used in some of the pieces described above is “really” VR. For example, Will Smith in an article in Wired127 argued that systems such as 360° video as might be seen through Google Cardboard should not be called “VR,” the main argument being that the relationship between head moves and image changes are more likely to lead to simulator sickness in 360°. However, this battle has already been lost. Mainstream media are already referring to 360° video as VR, and that is not going to change. In order to consider this question, we return to the concept of “immersion” discussed in Section 1.3. Immersion refers exclusively to the technical affordances of a system. Different types of immersion may give rise to different types of subjective experience, but this is a different issue. One system is “more immersive” than another if the first can be used to simulate the second. This can classify all systems into what mathematicians call a “partial order.” It is partial because that not all pairs can be classified in this way – there may be two systems where neither can be used to simulate the other.128 Now, if we consider 360° VR as video captured in a real setting and displayed in a head-tracked HMD then that can, in principle, be entirely simulated by a computer graphics rendering of the same scene, but not vice versa. By a graphics rendering of the scene we mean one based on a computer model (the model ultimately describes all the geometry, material properties, lighting, and dynamics of objects in the scene). Since there is a model, participants can change their point of view to anywhere within the scene. For example, they can move close to any object and then circle around it while observing it. If the viewpoint is restricted to only a few specific points, where from those points the viewer can turn around and look 360° then this is equivalent to “360-degree” VR. However, 360° VR cannot allow participants the full range of movement through the scene, to be able to observe any object arbitrarily from any angle. In normal vision based on natural sensorimotor contingencies, when we see one object obscuring another, we can move our head and in principle see completely behind the obscuring object. This can be done with correct perspective and head movement parallax in graphics-based VR. This cannot be done, or to a very limited extent in 360° video. Graphics-based VR can be restricted to simulate the 360° simulation, but not vice versa. Therefore, there is a fundamental technical difference that will always persist by definition between 360° and model-based VR. Model-based VR can simulate 360°, but not vice versa. Therefore, technically it has a greater immersion in this classification of systems. Ultimately, this means that they are useful for different purposes. If the VR is meant to depict something up-close and personal, such as interaction with a virtual character where the participant and virtual character might be arbitrarily changing their positions in the space, then this cannot be accomplished by 360°, since this type of parallax effect (e.g., just moving the head to see behind the character) just is not possible, unless every possible move that the participant was going to make was determined in advance and camera data made available for these possibilities. On the other hand, for a large-scale scene such as witnessing street protests as in’s Hong Kong protests mentioned above, then 360° is sufficient. Provided that the designers did not intend the possibility for a participant to move up close to any arbitrary protestor for one-on-one unplanned interaction then this is fine. Therefore, we would conclude that model or graphics-based VR and 360° VR are different possibilities in the domain that is referred to as “virtual reality,” and designers and application builders will use the type of system that fits best with their goals. For close-up interaction, 360° will quickly break the natural sensorimotor contingencies that are necessary for the generation of presence. On the other hand, for large-scale scenes looking at objects far enough away, 360° is not only the simpler form of construction and rendering, but it is good enough in terms of sensorimotor contingencies. It is not either one or the other, both have their role. A major worry of Will Smith is that one would be confused with the other, and that people with poor experiences in 360° will therefore label “virtual reality” as poor. Sensible and careful use of both types of technology where they are most appropriate would avoid this possibility. It should be noted that it is not the model-based solution in itself that is important here, but what it offers in terms of natural sensorimotor contingencies for perception. There will eventually be other solutions that are not model-based but offer the same. One likely solution will be based on light fields (Levoy and Hanrahan, 1996; Ng et al., 2005), which attempt to fully simulate the propagation of light through an environment, and therefore allow a viewer to dynamically move anywhere within a scene. The problem is that dynamic changes to objects, and especially changing lights, cannot easily be supported. Some recent developments for HMDs based on light field displays are discussed in Lanman and Luebke (2013). In this article, we have mainly reviewed developments in VR that have taken place since its origins in the 1980s, focusing on applications, and especially those with outcomes that have some level of research support. The field is changing extremely rapidly, and the inventiveness of people is amazing, with new ideas and projects emerging daily. Here, we briefly list some recent ideas that have caught our attention (as of May 2016). Mostly, these are ideas in progress, with no results, or maybe not even any level of implementation. They are presented in random order. Mark Zuckerberg: Virtual Reality Might Be Coming to Your Baby Photos The idea that VR may be used to share photos immersively. Dreams of Dali A VR experience based on Dali’s 1935 painting Archeological Reminiscence of Millet’s “Angelus.” Visualizing Big Data How “big data” in particular a longitudinal social survey can be explored in HMD-based VR. Topshop – London Fashion Week Attend the show using VR. A History of Cuban Dance A 360° VR documentary. Second Life in VR San Francisco Business Times reports “In virtual reality, Second Life prepares for its second act.” Megadeth in VR A YouTube documentary about Megadeth bringing heavy metal to VR. In the eyes of the Animal A Sundance Festival winner showing views of how the world might look to various animals Virtual Reality in Court A Popular Science report “Scientists Want To Take Virtual Reality To Court – Jurors May One Day Visit Crime Scenes Using Forensic Holodecks.” Project Nourished – A Gastronomical Virtual Reality Experience “You can eat anything you want without regret.” Curing Cataract Blindness NDTV report “Virtual Reality Could Be The Next Big Thing In Curing Cataract Blindness.” Oculus Quill Drawing in VR. Producer of Acclaimed “First” Sets Sights on Anne Frank VR Experience Plans for a historical VR reconstruction of aspects of the life of Anne Franke. Step inside the Large Hadron Collider (360 video)—BBC News “A 360 tour of CERN that takes you deep inside the Large Hadron Collider—the world’s greatest physics experiment—with BBC Click’s Spencer Kelly.” And so on… We have reviewed numerous applications of VR many of which were already envisioned or developed in its earlier forms in the 1980–1990s and have been more extensively developed and tested in the last 25 years. In most cases, the societal reach has been restricted given that the VR systems used (in combination or not with robotics, tracking, etc.) were too costly to move out the research laboratories and reach consumers. There has nevertheless been significant testing and validation of potential applications in many different areas. This article has shown that the applications of VR are very extensive and range across numerous domains of knowledge. This means that even though the most frequent use that the mass of people are going to experience as a consumer product will probably be for games and entertainment, all advances and developments in VR will also have an impact in more specialized research and professional fields. More affordable systems will facilitate not only the reach to final consumers but also to more developers and research groups, resulting in a much wider range of applications and generation of content for VR that will emerge in the near future. Even though applications in psychology, medicine, education, or research will reach many, there are some sectors of the population that may be also directly benefited from VR: those with reduced mobility for any reason, lesions, neurological disorders, or aging. To such people VR may provide a new space to move freely, interact, or work. This could be achieved by acting in VR through various means including motor action, BCIs, eye tracking, or physiological responses. Finally, we also point out that since the use of VR in these many application realms should be evidence-based, that scientific papers should adhere to the highest standards of rigor and reporting. In the hundreds of papers we have reviewed in the preparation of this article, there are many that do not even say what type of equipment was being used. The term “virtual reality” has been overused, when scientific papers are often simply talking about a PC display with a mouse, and the reader has to look very hard through the paper in order to discover that – if is stated at all. “I’ve seen things you people wouldn’t believe; attack ships on fire off the shoulder of Orion. I watched C-beams glitter in the dark near the Tannhäuser Gate. All those moments will be lost, in time, like tears in rain. Time to die.” (Replicant Roy Batty, near the closing scene of the movie Blade Runner).129 In the introduction to this article, we defined our notion of “immersion” as the “physics” of a system – how well it can afford people real-world sensorimotor contingencies for perception and action. We pointed out that this also offers a way of ordering systems – where one system is “more immersive” than a second if the first can be used to simulate experiences on the second, but not vice versa. We used this classification, for example, to show that model-based VR is “more immersive” than 360° VR, so that these have different functionality and uses. Yet, this raises a paradox. Immersive VR simulates experiences of physical reality. Does that mean that VR is more “immersive” than reality? Like any paradox, this helps us to understand the underlying concepts. There must always be some aspect of the VR that does not conform with reality. This is certain. Why? Because were it not the case then what the participant experiences would be his or her reality! This is not word play but rather illustrates a fundamental aspect of VR. The reader may respond – “Yes, but it is only a matter of time before the graphics, sound, tracking, haptics, etc. become so advanced that people will not be able to distinguish a VR experience from a real one, just like nowadays it is becoming difficult to distinguish pictures or videos that are photographs of real world scenes from those that are wholly generated by graphics.” However, in order for the VR to be indistinguishable from reality, the participant would have to not remember that they hadgone intoa VR system. Even if the devices become almost completely transparent and just a part of normal clothing, still the participant has to not know, in other words, has to forget that this is VR, has to forget pressing the button, or having the right thought in a BCI that commands: “Now put me into VR.” If it goes so far that they do not remember getting into VR and they consider that they are directly perceiving physical reality, then they are perceiving their own physical reality. When we think of VR we are typically thinking about experiences in the visual and auditory domains, rather than haptics (touch and force feedback). The field of haptics has excellent solutions for specific types of interaction, such as pushing a needle through soft tissue (as in medical applications), or using an exoskeleton to apply force feedback to an arm. However, unlike the visual and auditory fields, there is no generalized solution. By a generalized solution we mean a single device whereby participants in a VR can feel anything (just as a display can be programmed to display anything), for example, feel something when their virtual body accidentally brushes against a virtual wall or fall backwards when hit by a tidal wave of virtual water. As argued by Slater (2014), solutions to such issues may well have to go down the route of direct brain interfaces to solve such fundamental problems in a general way that can never be solved with external devices, which in the haptics domain always provide very specific stimuli. VR would become an applied branch of neuroscience in this view. Since as we and others have argued before our notion of reality is a constructed one, by activating the appropriate brain areas, our perception in this type of VR based on direct neural intervention would be indistinguishable from perception of “reality.” As the philosopher Thomas Metzinger has pointed out130 we are about to embark on an enormous process of new learning through mass availability of VR: “The real news, however, may be that the general public will gradually acquire a new and intuitive understanding of what their very own conscious experience really is and what it always has been” – that our conscious experience is one possible model – an interpretation – of the world. Now, let us imagine the perfect VR system with perfect immersion, so perfect that for most people it is completely indistinguishable from reality – it is their reality (recall that they must not remember that they “went into VR” and likewise they must not know when they “come out of VR”). Again seemingly paradoxically in such a situation the notion of presence vanishes. There is no sense of presence in physical reality. Presence is the feeling of being transported to another place. This is why our notion of “place illusion” as “being there” includes the rider “…in spite of the fact that you know for sure that you are not actually there.” It contains an element of surprise: “I know I am at home wearing a HMD, but I feel as if I am in the Himalayas.” In physical reality, there is no perceptual surprise, no feeling “Wow! Look at that, it is amazing that I am here!” (except, for example, as a way of expressing good fortune at being in a fabulous place). We are just “here.” We do not comment on it or think about it from the perceptual point of view – only sometimes at the content of our perception – the scenery or surprising events. There is no special or remarkable feeling associated with being in a place. It is how things always are. The only time we might feel something unusual is when some aspect of our perception breaks – for example, through mental illness, hallucinogens, the aftermath of an injury – where we find ourselves outside of the reference frame of our normal perception. In the movie The Matrix,131 almost everyone was living in perfect immersion, perfect VR. They only became aware of “presence” (i.e., that their world was illusory) at moments when the system failed. Hence, the illusion of presence actually represents the non-perfection of immersion. On one side, as we improve immersion more and more through technical advances what this means in terms of “presence” is that the “wow” factor, the sensation of the difference between where we know ourselves to be, but where we feel ourselves to be, i.e., the level of illusion, will become stronger and stronger. The shock of putting on the HMD and seeing an alternate reality in high-resolution, all around, with fantastic vision, sound, haptics, smell, taste, and full body tracking will become overwhelming. But, on the other side, when immersion becomes perfect – to the point that we do not in any way distinguish between perception of reality and VR even to the extent of not knowing when we are perceiving from one rather than the other – then presence will disappear. However, it is also possible that the surprise element of “presence” will disappear for another reason. Imagine the generation that grows up where VR is just as much part of their lives as cell phones are today. Although they will distinguish reality from VR, their illusion of presence may diminish because the surprise element will disappear through acclimatization. Older generations today still marvel at being able to have real-time video connections at virtually zero added cost with people half way around the world, but a younger generation that is growing up with that find it completely unremarkable. So, this new generation that grows up with VR will of course have the illusion of “being there” in VR, but it will be nothing special, and therefore there will be all the more reason that they will tend to behave the same in VR as they do in reality in similar circumstances. It will be like: Now I am at home. Now I am at school. Now I am in place X in VR. They will become equivalent perceptually, cognitively, and behaviorally. But, just as kids learn “Don’t run in the school corridor,” “Don’t shout in the classroom,” so they will learn different forms of behavior that apply to different places in different modes of reality. VR will have its own customs, norms of behavior, and politeness. Today all we can say is that however we imagine this might be – it won’t be like that, since it will be the result of an unpredictable and complex product of technological advance and social evolution. We have used the term “presence” slightly loosely here. Recall that there are two components: PI (resting as a necessary condition on sensorimotor contingencies) and Psi (the illusion that events are real). The latter is just as critical and maybe more difficult to get right in many applications. For example, in a real street we might avoid parking our car because we see a police officer standing nearby. On closer inspection we realize that the police officer is actually a manikin dummy. So we park. This is a failure of Psi of the dummy. In VR, we are enjoying talking to a very nice virtual person. Eventually, we realize that the virtual person is going through some repetitive actions and is not actually aware of what we are doing. We move away. This is a failure of Psi, even though our illusion of being in the place is intact. Both PI and Psi are critical components of successful VR applications. Virtual reality, however, can deliver forms of Psi that have never existed in reality and yet still lead to the illusion of these happening. In Slater et al. (1996), we put people in a VR where they could play 3D chess (like in Star Trek). Not one person was shocked or made any comment about the fact that when they touched the chess pieces these would float in the virtual space to their next location. When asked about this one participant said: “Oh that’s just how things behave in this reality.” So Psi is a difficult concept. In some circumstances, expectations cannot be broken. In others VR can create new expectations that seem completely natural even though they could never happen in physical reality. This is something really worth understanding, and it is connected to our final point. Virtual Reality encompasses virtual unreality. Almost all the applications we have reviewed, and a lot of what we see, translate something from reality into VR. A fear of heights application puts people … on a height. A fear of public speaking application puts people … in front of an audience. These are fine. However, maybe there are completely new ways to think about these types of applications that make use of the amazing power to put people outside of the bounds of reality and have a positive effect. Even though VR has been around for half a century, still not enough is known about it. The goal is to shape it to create moments that enhance the lives of people and maybe help secure the future of the planet. And those moments need not be lost.132 All the authors listed have made substantial, direct, and intellectual contribution to the work and approved it for publication. The authors were approached by the company Facebook to write an article on potential applications of VR. After completion, the article was subject to a review by the Facebook legal team. There was neither implicit nor explicit encouragement to promote or favor any Facebook products or services. The authors were free to write about virtual reality as they wished. The work is a review of virtual reality in general and not related to any particular products, software, or services. Thanks to James Hairston of Oculus for his support of this work. In addition, the authors thank the following people who have provided images or video that appear in the Supplementary Presentations: Abderrahmane Kheddar, Aitor Rovira, Albert ‘Skip’ Rizzo, Anatole Lécuyer, Angus Antley, Anthony Steed, Antonio Frisoli, Barbara Rothbaum, Christoph Guger, Daniel Freeman, Doron Friedman, Emmanuele Tidoni, Ferran Argelaguet, Franck Multon, Franco Tecchia, Greg Welch, Henry Fuchs, Henry Markram, Hunter Hoffman, Jeremy Bailenson, Jordi Moyes Ardiaca, Larry Hodges, Louis Jebb, Lucia Valmaggia, Mark Huckvale, Nonny de la Peña, Pablo Bermell, Pere Brunet, Rafi Malach, Robert Riener, Salvatore Aglioti, Stephen Ellis, Sylvie Delacroix, Will Steptoe, Xueni (Sylvia) Pan, Yiorgos Chrysanthou, and Zillah Watson. This work was funded by Oculus VR, LLC, a Facebook Company. The Supplementary Material for this article can be found online at Abulrub, A.-H. G., Attridge, A. N., and Williams, M. 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No use, distribution or reproduction is permitted which does not comply with these terms. *Correspondence: Mel Slater, [email protected]
, , Sylvie Boermans, Melissa Desmedt, Sam Pless, Steven Van Den Oord, Nick Verhaeghe, Geert Van Hootegem
Published: 17 October 2017
International Journal of Integrated Care, Volume 17;

Introduction: In November 2013, a 4-year research project on integrated care in Flanders (Belgium) was launched: “Care Organisation: a Re-Thinking EXpedition in search for Sustainability” (CORTEXS). Expertise on management, organization sciences, social innovation, patient participation, health law, patient safety, care quality and health economics was brought together. CORTEXS closely cooperates with over 30 stakeholders from policy and practice. The project will end in Octobre 2017. The multidisciplinary research team focuses on the fundamental challenge which many care systems face: how to organize care integration? The CORTEXS team developed a social systems based approach for redesigning care systems, resulting in a comprehensive framework of redesign principles, contextual preconditions, and care system performances. We submitted a proposal for an oral presentation in a plenary session, where we plan to present this comprehensive framework:Dessers E. e.a., Organizing integration of care: a social systems based approach. Results from Project CORTEXS (Flanders, Belgium).The framework is based on extensive theoretical and empirical work that has been done by the CORTEXS researchers over the past years. The main goal of this special symposium session is to present some major results from the various CORTEXS substudies, followed by Q&A and discussion. The presence of a broad delegation of eight CORTEXS research team members, including the project coordinators, will assure extensive and in-depth coverage of the different aspects of the CORTEXS research project.Theory/Methods: A comprehensive research design was developed to integrate multiple disciplines, methods and levels of analysis, and to support both theory- and action-based research. Integrated care was studied from the micro-level of care recipients and their informal caregivers, over the meso-level of intra- and inter-organizational processes, to the macro-level of legal and financial frameworks. At each level, the most appropriate research methods are applied, including document analysis, process mapping, network analysis, legal analysis, comparative case analysis, economic modeling, and patient and care worker surveys. Results from the various substudies are integrated trough social lab sessions, business canvas model exercises, and simulation gaming in order to explore future options for realizing care integration. Furthermore, CORTEXS actively stimulates transfer, exploitation and utilization of the research results.Results: The session aims to group the following oral presentations (which have been submitted separately via the conference submission tool).The first two presentations are on redesign principles, within organizations and organizational networks.Pless S., e.a., Analyzing Task Division, Coordination and Continuity of Care in Care Processes. A Comparative Case Study of four Specialized Multiple Sclerosis Hospitals [CORTEXS]van den Oord S., e.a., The Governance, Structure and Management Processes of an Emergent Goal-directed Organizational Network: an Evaluation of a Configurational Framework of Goal-directed Networks.The next two presentations focus on preconditions for redesigning care systems, in the field of financial incentives and information technology.Verhaeghe N., e.a., Financial Incentives for Integrated Care for People with Chronic Conditions in Belgium: a Qualitative Study within the CORTEXS Research ProjectBoermans S., e.a., Information technologies and patient engagement for in integrated care: Lessons from an international comparison for the CORTEXS-project.The fifth presentation is about care system performance, in terms of care quality and safety.Desmedt M., e.a., Quality and Safety of Chronic Illness Care through Patients’ Eyes (CORTEXS).The final presentation deals with the application of the CORTEXS redesign principles for reorganizing mental health care networks.Van Hootegem G., e.a., Organizing mental health care networks. Testing the CORTEXS redesign approach.The presentations are followed by Q&A and discussion, moderated by the session chairs.
, , Nevin Cohen, Terry T. K. Huang
Published: 25 October 2021
Frontiers in Public Health, Volume 9;

In the United States, enrollment in online education has increased over the last decade. By fall of 2018, one third of almost 19.7 million students enrolled in degree-granting post-secondary institutions had enrolled in online courses with nearly 40% of graduate students taking online courses (1, 2). Among 120 CEPH-accredited schools of public health, 57 schools have fully online programs and 48 have hybrid online and on-campus models (3). During the COVID-19 pandemic, universities and colleges across the United States were forced to shift rapidly from in-person education to “emergency remote learning” with little time to redesign courses and programs appropriately (4). Several challenges made the transition difficult: limited resources due to pandemic-related costs and revenue losses; equipment and workspace constraints for students; and misunderstandings about the pedagogical differences between instructional modes. Schools and programs restricted by hiring freezes and reduced budgets made it difficult for instructors to plan, build and manage courses, and to get extra help to use new technologies. The shift to remote learning also exposed that many students lacked resources and capacity to continue their education online, including unreliable internet access and computer hardware and inadequate space and time conducive for study. Without training in online education or resources to develop different types of courses, many faculty simply tried to replicate online the methods of teaching they had been doing in-person. The pandemic-induced shift online presents substantial problems and pressure for academic services and support units. We propose three ways that schools and programs can respond: (1) training faculty on pedagogy and the technology that enables online learning; (2) improving student readiness and preparation for online education; and (3) reimagining educational offerings that respond to skills in demand. Together, these strategies will help programs and schools keep pace with peer institutions with well-developed online programs. With the exception of undergraduate colleges that emphasize teaching, faculty in graduate schools are often rewarded more for research skills than teaching acumen. Most instructors learn to teach by doing, copying the kind of instruction they received in college and as teaching assistants. An assistant professor may have only practiced teaching a handful of courses before having to manage a 4–6 course teaching load. For instructors with limited to no experience teaching online, the abrupt shift to remote teaching proved highly disruptive and stressful, forcing many to do the best they could in a very difficult situation. Delivering a course online is not simply recording and making available hour long lectures. Designing an effective online course requires partitioning didactic material into shorter “chunks” and micro-lectures followed by a variety of assessments such as quizzes, games, real-world based simulations, discussions led by students as moderators, icebreaker activities, and microblogging to keep students engaged (5). Online courses are designed with navigation and structured modules to facilitate how the student flows through the course. Modules should contain different types of assessments and activities to reinforce skills. These may be group-based or individual projects with appropriate selection of software and hardware (6). Instructors should sustain instructor presence and facilitate learner-to-learner interaction on a regular basis. Especially for online courses taught for the first time, formative evaluation is important to check how students are responding to the structure, navigation, activities, and peer interaction. These are some of the skills necessary to successfully develop and manage an online course (7). Properly designed online courses require instructional design and technology expertise. Instructional designers have expertise in reworking instructional material for different modalities and instructional goals. It is also very useful to identify a group of instructors and colleagues experienced in online learning in order to share tips and advice. This could lead to learning communities within the organization to support each other as online courses are introduced and refined every semester. Schools and programs should ensure that instructors of all ranks have access to expertise and centers of teaching and learning. Centers of teaching and learning typically provide training in basic instructional design, accessibility and universal design for learning (UDL) principles, and adult pedagogy techniques. Online modes offer opportunities that in-person courses do not: easier and more robust peer interaction and learning; access to more geographically diverse student bodies; different student demographics including older students, students with jobs and family obligations, students with physical disabilities; more time for students to interact with and learn from people within their communities; and greater and more even participation in course activities. Many instructors have looked to technology as the solution, but technology only works if tailored to meet instructional goals that are grounded in effective and evidence-based pedagogy. Delivering online courses synchronously without modifying instructional strategy may lead to disappointing results and may exacerbate inequities, particularly among students from disadvantaged backgrounds (8). Just as sitting in a classroom does not ensure that a student is learning, being on a Zoom conference does not ensure learning; the mode of interaction in both cases needs to be designed to engage students in active and meaningful learning. Large variability in teaching quality already exists in traditional in-person classrooms. Online education may be particularly risky business for schools that do not have properly trained and supported...
Tarrant J. Falcke, , David J. Brennan, Sarah E. Sinclair
Published: 1 January 2011
Process Safety and Environmental Protection, Volume 89, pp 41-52;

The publisher has not yet granted permission to display this abstract.
Ana Filipa Guedes, , José Braz-Nogueira, Nuno Lousada, Carlos Moreira, ,
Published: 19 January 2018
Annals of Medicine, Volume 50;

Erythrocyte aggregation is an indicator of cardiovascular risk, which is influenced by plasma fibrinogen concentration. Fibrinogen levels are elevated during cardiovascular diseases. Our main goals were to understand how fibrinogen-erythrocyte binding influences erythrocyte aggregation and how it constitutes a cardiovascular risk factor in essential arterial hypertension (EAH) and chronic heart failure (CHF). Fibrinogen-erythrocyte and erythrocyte-erythrocyte adhesion measurements were conducted by atomic force microscopy (AFM)-based force spectroscopy. Upon increasing fibrinogen concentration, there was an increase in the work and force necessary for cell-cell detachment, both for healthy donors and EAH patients. Nevertheless, higher values were obtained for the EAH patients at each fibrinogen concentration. Fibrinogen-erythrocyte (un)binding forces were higher in EAH and CHF patients, when compared with the control group, despite a lower binding frequency. Ischemic CHF patients showed increased binding forces compared to non-ischemic patients. Erythrocyte deformability (assessed as elongation index) results show that heart failure patients presented higher erythrocyte deformability than the control group at lower shear stresses, and lower deformability at higher shear stresses. This indicates that patients’ erythrocytes are more deformable than those from healthy donors in blood vessels with larger internal diameters; however, in smaller-diameter vessels the opposite trend exists. Finally, a 12-month clinical follow-up shows that CHF patients with higher fibrinogen-erythrocyte binding forces, probed by AFM at the beginning of the assessment, had a significantly higher probability of being hospitalized due to cardiovascular complications on the subsequent year. Our results show that AFM can be a promising tool for clinical prognosis, pinpointing those patients with increased risk for cardiovascular diseases. Inflammation and calcification-related diseases are pathological processes involving several factors and a complex interplay between inflammation and calcification events that lead to disease progression. Gla-rich protein (GRP) is a vitamin K dependent protein (VKDP) () shown to function as a calcification inhibitor in cardiovascular [] and articular tissues [] and as an anti-inflammatory agent in chondrocytes, synoviocytes and monocytes/macrophages [,,]. In a context of chronic inflammation and calcification-related pathologies, GRP is able to act as an endogenous mediator of inflammatory responses and a novel molecular mediator linking inflammation and calcification events, with potential therapeutic application (). Vascular calcification (VC) is highly prevalent in chronic kidney disease (CKD) and associated with increased morbidity and mortality. This complex process, known to be associated with inflammatory status and enhanced by inflammatory cytokines, relies on the presence of systemic and local calcification inhibitors like fetuin-A and Gla-rich protein (GRP). Increased levels of calcium (Ca), and Ca phosphate product in circulation have been related with increased frequency of VC in CKD. The study of circulating nanoparticles as calciprotein particles (CPPs) and extracellular vesicles (EVs) and their pathophysiological role and mechanistic link, with the prevalence of vascular calcification in CKD patients, is greatly highlighted. In particular, results on the association of GRP with CPP and circulating EVs isolated from CKD patients show a higher mineral content and reduced levels of GRP and fetuin A, when compared with healthy controls. Moreover, the study of the effect of these biological CKD nanoparticles in VSMC calcification, differentiation and inflammation, reveal its pro-inflammatory and mineralization pathogenic activity. In conclusion, in a context of chronic inflammation and calcification-related pathologies, GRP acts as a novel molecular mediator linking inflammation and calcification events, with potential therapeutic application. This also precludes a great potential use for GRP, as part of circulating EVs and CPPS, for the diagnostic of these highly prevalent vascular calcification-related diseases. Acknowledgements: This work was funded by projects PTDC/SAU-ORG/117266/2010, PTDC/BIM-MEC/1168/2012 and project UID/Multi/04326/2013, all from the Portuguese Science and Technology Foundation (FCT) and UCIBIO-REQUIMTE. Aquaporins (AQPs) are membrane channels that transport water and glycerol across cell membranes and are crucial for many biological functions. Mammals AQPs (0-12) have essential roles in health and disease, suggesting that their modulation may have broad therapeutic potential. Detecting AQPs expression and function in cells and tissues is critical for screening modulators for the development of efficient medicines []. We have disclosed inhibition of the aquaglyceroporin AQP3 by gold-based compounds [] and highlighted the relation between AQP3 expression, glycerol permeation across cell membranes and cell proliferation []. The mechanism of inhibition has been recently described using molecular dynamics, combined with density functional theory and electrochemical studies []. The selectivity of gold compounds towards aquaglyceroporins was confirmed by its inhibitory effect on AQP7, largely expressed in adipocytes and important in adipose tissue homeostasis and obesity []. By facilitating glycerol efflux from adipocytes during fasting and its uptake into the liver for gluconeogenesis, aquaglyceroporins are emerging as key players in adipose tissue homeostasis and insulin response with potential implications in obesity and metabolic-related complications []. AQPs are also involved in tumor invasion, metastasis and growth []. Our recent studies pointed to a role of AQP5 on adipocyte cell differentiation [] and its involvement in cell oxidative stress response by facilitating hydrogen peroxide permeation across membranes []. Interestingly, we have also detected aberrant expression of AQP5 in pancreatic tumors of high malignancy, suggesting it may be used as a biomarker for early diagnosis []. Altogether, our studies highlight AQPs as promising drug targets in obesity and cancer. Nosocomial infections caused by multidrug-resistant bacteria represent a growing problem worldwide and are well documented. There are statements by the WHO and CDC describing a global crisis and an impending catastrophe of a return to the pre-antibiotic era. Metagenomic studies have revealed homologues of known resistance genes broadly distributed across environmental locales and allowed the formation of a database with more than 20,000 potential resistance genes predicted from available bacterial genome sequences. However, the number of resistance determinants functional in pathogens are much smaller. The widespread dissemination of antibiotic resistance elements is inconsistent with a hypothesis of contemporary emergence and instead suggests a richer natural history of resistance. Several mechanisms are responsible for the emergence and prevalence of antimicrobial resistance, and such mechanisms have been divided into genetic mutation occurred at a low frequency and acquisition of various genes among bacteria. All the known antibiotic resistance mechanisms, acquired by opportunistic and pathogenic bacteria, evolve mutations occurring in pre-existing genes of the bacterial chromosome positively selected by environmental forces and can be responsible for the decreased affinity of antibiotics to their targets. Acquisition of resistance genes has been regarded as major contributor for the wide distribution and spread of antimicrobial resistance, via either vertical transfer or horizontal transfer, with the latter mechanism involving mobile genetic elements such as plasmids, transposons, integrons and bacteriophages. The role played by these elements among bacteria has been well established and documented, which had also been considered to contribute to the unleashing of “Super Bugs”. However little is known about the diversity and origin of resistance genes among the unculturable environmental bacteria. The soil is one potentially rich but largely unstudied reservoir. The complexity of its microbial community coupled with its high density of antibiotic-producing bacteria makes the soil a likely origin for diverse antibiotic resistance determinants. This raises many questions about the natural functions of environment. Recently, there are evidences that environmental habitats especially waterbodies such as rivers and streams are ideal vectors for the antibiotic resistance dissemination. The emergence and rise of antibiotic resistance observed worldwide cannot be explained only by the increasing modern use of antibiotics in humans, but involves a complex interaction in an ecosystem comprising microbial communities, antibiotics, and antibiotic resistance genes. The human oral cavity holds one of the most diverse microbiome in the human body. It includes viruses, fungi, protozoa, archaea and bacteria. These microorganisms regulate each other and coexist within the microbial community. They can be found in complex biofilms attached to soft and hard tissues assembled in an ordered process that begins with adherence of microbial colonizers to a surface followed by attachment of different microbial species to initial colonizers. The presence of these microorganisms may affect the wear. In order to understand the impact of the presence of bacteria on the dental materials testing two tribological systems were studied: zirconia dental crown against natural teeth and zirconia abutment against titanium implant. Thus in order to evaluate the effect of the presence of bacteria a nom cariogenic bacteria was selected: Streptococcus salivarius (S. salivarius). The bacteria growth profiles were studied in artificial saliva with three different nutrients (meat extract, urea and glucose), pH (from 5 to 9) and motion conditions (static and movement) in order to set the wear tests. Reciprocating pin on plate tests were performed for both tribological systems (human cusps/zirconia plates and Ti6Al4V ball/zirconia plates) using three lubricants: artificial saliva, artificial saliva with glucose and artificial saliva with glucose and S. salivarius, at a temperature of 37 °C and pH 7. The best bacteria growth condition were found for glucose as nutrient, at pH 7 and without motion. For the tribological system human cusps/zirconia plates the results showed that the presence of bacteria reduced the friction coefficient, dental wear loss and reduces de thickness of the smear layer formed on the worn surfaces. For the tribological system Ti6Al4V ball/zirconia plates the results revealed that bacteria reduced the titanium wear and the titanium corrosion activity during wear. Over all, the presence of S. salivarius leads to a dramatic changes of the tribological performance of the tested dental materials. Acknowledgements: The authors are grateful to Fundação para a Ciência e Tecnologia (FCT, Portugal) for financial support under project Pest-OE/CTM/UI0084/2014. To promote resin polymers adhesion to dentin, the mineral phase from the substrate has to be removed by acids and the voids left by mineral should be filled with the adhesive resin that undergoes complete in situ polymerization to form the hybrid layer. It is generally accepted that there is a discrepancy between the depth of demineralization and the depth of resin infiltration. Matrix metalloproteinases are present in dentin and contribute to collagen degradation at the dentin–resin bonded interfaces, jeopardizing the longevity of bonded restorations. A decrease of bonding efficacy over time has been reported and attributed to the action of host-derived MMPs. Therefore, one of the proposed strategies used to increase the longevity of adhesive restorations has been to inhibit the MMP-induced degradation of dentin collagen [,]. Zinc effectively reduces the MMP-mediated degradation of collagen in dentin [,]. It seems that subtle conformational changes occur in collagen following zinc binding and lead to the protection of sensitive cleavage sites of metalloproteinases. Moreover, zinc is able to promote dentin remineralization [,]. Zinc and phosphate are important for hydroxylapatite homeostasis. Scholzite formation was encountered in dentin stored in zinc-containing solutions []. Zinc might allow to reach the balance between dentin demineralization and remineralization processes. Thus, the zinc concentration around matrix-bound MMPs might be very important in determining longevity of resin-dentin interfaces []. Acknowledgements: This work was supported by the Ministry of Economy and Competitiveness (MINECO) [Project MAT2014-52036-P] and European Regional Development Fund (FEDER). Introduction: The aim of this study was to evaluate the effectiveness of different nanogels-based solutions for dentin permeability reduction and to determine the viscoelastic performance of cervical dentin after their application. Materials and Methods: Four experimental nanogels based on zinc, calcium or doxycycline-loaded polymeric nanoparticles (four products) were applied on citric acid etched dentin (fifteen specimens) to facilitate the occlusion and the reduction of the fluid flow at the dentinal tubules. After 24 h and 7 d of storage, cervical dentin was evaluated by a highly sensitive fluid filtration system. Field emission scanning electron microscopy, energy dispersive analysis, AFM and Nano-DMA analysis were performed. Complex, storage, loss modulus and tan delta (δ) were assessed []. Results: Tubules were 100% covered in dentin treated with Ca-nanoparticles and Zn-nanoparticles, analysed at 24 h and 7 d, respectively. All tubules were visible after 7 d when dentin was treated with Ca-NPs, and 95% of them were filled. Dentin treated with both Zn-nanoparticles and Ca-nanoparticles attained the greatest reduction of dentinal fluid flow. The complex modulus and the tan delta between peritubular and intertubular dentin treated with Zn-nanoparticles was bigger than that obtained with when Ca-nanoparticles, showing zones of stress concentrations with dentin structure breakdown []. Discussion and Conclusions: Crack-bridging with frictional pullout due to precipitation of minerals were produced. This mineralization, as sight of energy dissipation, improved the sealing of the micro-cracks and the hydraulic conductance of dentin [,]. Acknowledgements: This work was supported by the Ministry of Economy and Competitiveness (MINECO) [Project MAT2014-52036-P] and European Regional Development Fund (FEDER). Introduction: Thermography is a non-radiating and contact-free technology which can be used to monitor skin temperature. The efficiency and safety of thermography make it a useful tool for detecting and locating thermal changes in skin surface. Being a non-invasive technology, the interest of its application in the field of health has been growing, with its application in biomechanics domains. This work intends to be a contribution for the use of thermography as a methodology for evaluation of skin temperature in the context of orofacial biomechanics. The study aims to identify the oscillations of skin temperature in the left and right hemiface regions of the masseter muscle, before, during and after ice therapy. The study involves the observation of the recovery with and without an induced stimulus based on the use of a chewing gum. Materials and Methods: Using a FLIR T430sc camera, a data acquisition protocol was followed with a group of 8 volunteers, aged between 22 and 27 years. The tests were performed in a controlled environment with the volunteers in a comfortably static position. The thermal stimulus involves the use of an ice volume with controlled size and contact surface. The skin surface temperature was recorded in two distinct situations, namely without further stimulus and with the addition of the induced stimulus. The thermal data obtained were treated using FLIR Research IR Max software. The considered emissivity was set to 0.98, the normal value for the skin []. The statistical analysis of the results was performed with RStudio Software. Results: The results obtained show that the time required to recover until the initial temperature ranged from 20 to 52 min when no stimulus was added and ranged between 8 and 26 min with the chewing gum stimulus. The analysis of the results reveals a variation of averages with statistical significance when comparing the application and absence of stimulus with a p = .4756 (p > .05). Discussion and conclusions: This work, despite the reduced sample, intends to demonstrate the utility of thermography in the study of some aspects of orofacial biomechanics. In fact, the applied methodology clearly shows a decrease in the time needed to reestablish the initial temperature when implementing a simple chewing gum stimulus. This can be due to the increase in metabolic recruitment of the muscle by the chewing process, with an increase of blood circulation on muscle metabolism and by the neutralizing effect of the vascularization itself increased by the function. In other hand, dentists should be aware that with the current ice protocols they are most likely to be maintaining skin temperature in lower values for longer times, raising questions of potential iatrogenic effects and tissue hypothermia by maintaining a temperature much lower than normal values. However, these questions remain unclear and not studied in the literature. Acknowledgements: The authors would like to thank for LBA – Applied Biomechanics Laboratory from Polytechnic Institute of Coimbra and also all volunteers of the study. This research was sponsored by the project UID/EMS/00285/2013. Introduction: The last decade presented an unprecedented increase in the number of new psychoactive substances (NPS) released in the drug market []. Recently a new class of drugs known as NBOH started to be reported in many Brazilian States []. The NBOH compounds are N-benzylhydroxy derivatives of the 2C hallucinogen. The 25I-NBOH is a liable molecule that undergoes degradation when exposed to routine screening gas chromatography methods posing an extra challenge to correct identification as the main degradation product is another phenethylamine, 2C-I []. Materials and Methods: GC–MS analyses were performed on an Agilent 7890A gas chromatograph connected to a 5975C Mass Spectrometer (Agilent Technologies, Santa Clara, CA, USA.). An Agilent J&W HP-1MS fused silica capillary column was used. Sample injection volume was 1 μL with a 25:1 split ratio. Helium was used as carrier gas and injector temperature was 280 °C. The oven program: t 150 °C for 1.5 min, 30 °C min−1 to 250 °C hold for 1 min, and 50 °C min−1 to 300 °C hold for 3 min. Mass scan range was m/z 35–550. Results: Firstly, we present the GC–mass spectrometry (MS), liquid chromatography–quadrupole time-of-flight-MS, and Fourier transform infrared and nuclear magnetic resonance analyses to complete 25I-NBOH molecular characterization. Secondly, a GC-MS method that allows distinction between 25I-NBOH and 2C-I using routine GC–MS without resorting to derivatization is described. While direct detection of 25I-NBOH under routine GC conditions is still to be achieved, slight adjustments in standard GC methods, including shortening of the solvent delay window, enabled the detection of an additional peak containing 25I-NBOH degradation product’s fragmentation ions. Consequently, this secondary early chromatographic peak is characteristic of the 25I-NBOH, thus preventing misidentification. Discussion and Conclusions: With the active and continuous emergence of NPSs over the last years, most of them derived from previously known ones, correct identification of questioned samples becomes an increasingly subtler task, because some species of compounds undergo chemical changes during analysis, potentially leading to serious misidentification. In this context, forensic scientists dealing with routine GC–MS testing of seized samples should be mindful of this issue and be ready to recognize the possibility that such a change may take place during analysis, specially when solely relying on GC–MS. Introduction: Nowadays, journalism is one of the top ten most stressful occupations [] but it was only after 9/11, that research has come to acknowledge journalists as an at-risk occupational group, and to focus on the impact of the events they report on their health and well-being. A recent meta-analysis of studies from 2001 to 2015 on journalists’ occupational stress revealed that little is known about the differences and similarities between occupational stress experiences and variables of journalists in their daily work and in the context of reporting critical events []. Furthermore, there are no studies that try to identify the positive impacts on the life and health of these professionals and that use a theoretical occupational model as a backdrop to their research. Taking the occupational stress model [] as a framework, this study attempts to overcome this shortcomings by seeking to shed light upon the similarities and differences in occupational stress variables between daily work journalists and special envoys reporting major disasters, thus offering important contributions to theory and practice. This study also brings together both qualitative and quantitative data in the analysis of the variables under study, according to the number of deployments to a critical event. Method: 25 Portuguese journalists were interviewed on their perceptions of the core variables of the model []: occupational stressors, emotional reactions, coping and savoring strategies and the consequences of these experiences on their well-being, either in their daily context or critical scenarios. The number of times they had been abroad reporting a major disaster (natural or human made) was also questioned in order to ascertain whether repeated exposure to trauma influenced journalists’ occupational stress perceptions. Results: The data content analysis gave rise to 113 inter-related categories, structured in a hierarchical system. For the daily professional context of the journalists, 39 categories (35%) were identified while for critical events, 74 categories (65%) were constructed. Occupational stressors and emotional reactions differed across both settings, emotion-focused coping strategies were the most frequently mentioned for both settings, while savoring strategies were only referred to for critical events. Perceptions of coping strategies were four times more frequent than those of savoring. Consequences associated with journalists’ experiences were perceived as being mainly negative in both occupational contexts. Significant differences were identified in all of these variables according to the number of deployments to a critical event. Discussion and conclusions: This study offers a valid contribution to the understanding of occupational stress among journalists and it serves to alert media organizations to the fact that suitable preparation and support should be provided to journalists in their work performance. Funding: This work was supported by the Fundação para a Ciência e Tecnologia of Portugal [grant number SFRH/BD/41454/2007]. In this study we try to understand the experience of the return to everyday life of adults faced with a limit-situation; to make clear the experienced processes involved in the limit-situation and to describe the lived circumscribed experience and punctuating the return path to everyday life. It is based in the health existential concept within the framework of caring as a vital dimension of human behaviour, namely when the challenge is to safeguard and activate all that makes living and existence possible. The experience of the concrete possibility and close to finitude is a process present in the human response facing the disruption of a serious illness lived as a limit-situation. The phenomenological approach has permitted access to the narration of the lived experience of returning to everyday life. The meaning units are determined by the experienced moments – the way the subject relates to them, lives them in its own body and inscribes in the grammar of his/her existence – that trace them as analytical possibilities in the context of this study. The event is a threatening situation for the person due to the suffering, unease and strangeness experienced suddenly and expressed in the body, now the focus of all attention. The body is an object outside oneself, revealing the division body-consciousness. The event it triggers is not lived as an illness but as a struggle between death and life, each participant searching for meaning and reason in the context of existence. It is a threat to concrete survival, to the physical body, biologic in its vital functions. In this perspective, the return to everyday life, its existence in (his/her) world is seen as a “hard” work of surviving the fight it has begun, and, as it is solitary work, it lacks the presence and companionship of others. It is a transformation work of the self – to become another, better person. At first it is the work of delivering oneself from the disease in the body which is followed by silent and long work of freeing the disease from life which in turn translates into trusting the body that you are and “drop the illness’s routines, enter the everyday life circuit, and this is what best characterizes life and feeling healthy within it”. Introduction: Nursing practice care has been developed in an environment of increasing complexity []. Research shown that environment health organizations should be favorable to nursing professional practice and is fundamental to improve quality care provided. Many studies identify some traits of the organizational environment in which care are provided and influence client’s outcomes, nurses, and health organizations. Positive nursing practice environments are associated with better perceptions of nurses' quality of care and satisfaction [,]. The aim of this study was to evaluate nursing environment professional practice in four public portuguese hospitals. Materials and Methods: This study is a quantitative, observational, descriptive, cross-sectional study, with the research question: How nurses evaluate the organizational environment professional practice? To evaluate the nurses professional environment was applied the Portuguese version of the Revised Nursing Work Index (NWI-R). Ethical procedures such as informed consent have been followed. Of the 1304 nurses of four public portuguese hospitals, selected for the study who were invited, 767 nurses collaborated, responding to the questionnaires. Results: The nurses who participated in the study 83.4% are licensed, 84.2% female, with an average age of 37.24 years and 14.25 years of professional activity, 47.4% were working in medical units, 7.7% in Surgery and 44.9% in units of other types. The nursing professional practice environment had a generally positive assessment (mean of 3.33). All subscales that are defined in the study of Aiken [], Multidisciplinary Relation, Autonomy, Organizational Support and Control over the Environment - had positive averages with 3.55; 3.35; 3.30 and 3.12, respectively. Discussion and Conclusions: A professional nursing organizational environment was generally considered favorable. The Control over the Environment, Organizational Support and Autonomy are strongly conditioning of a conductive environment to the practice of nursing care. Contributions to consider to Nursing Management and Nursing Research should be considered.
, Wilfred Otten, Alexandra Kravchenko
Published: 7 June 2019
Frontiers in Environmental Science, Volume 7;

Editorial on the Research TopicElucidating Microbial Processes in Soils and Sediments: Microscale Measurements and Modeling Over the last decade, soils have become increasingly central to a number of crucial debates on issues of great societal concern, related to climate change, environmental pollution, or feeding the estimated 10 billion people who will live on earth by 2050, a mere 30 years from now (Baveye, 2015). In order to successfully meet the extremely daunting challenges that confront us in these different contexts, we need to understand what controls the growth and activity of the soil microorganisms that mediate many if not most of the underlying processes. However, the information we have in this respect is still woefully inadequate, arguably at least in part because of a lack of appropriate technology. Half a century ago, soil microbiologists reached the conclusion that a full understanding of the growth and activity of microorganisms in soils and sediments would require quantitative observations at spatial scales as near as possible to the size of the organisms themselves (Alexander, 1964). Back then, this type of observation was not feasible at all, unfortunately. The development of electron microscopes in the 60s and 70s provided qualitative insight into microscopic parameters that controlled the activity of bacteria, archaea, and fungi in pore spaces (Foster, 1988), but produced no quantitative information. It is only with the technological advances in X-ray computed micro-tomography (μCT), first at synchrotron facilities in the 90s, then with commercial table-top scanners in the early 2000s, that quantitative, micrometric data on the geometry of the pore space has finally become available. In the last decade, different methods have also been developed to measure the spatial distribution of microorganisms at fine resolution in thin sections (e.g., Nunan et al., 2001), as well as to map the composition of organic soil constituents (e.g., Solomon et al., 2005) or the nature of nitrogenous compounds at micrometric or even nanometric scales (e.g., Mueller et al., 2012, 2017). After these novel techniques became available, an initial stage in the research has consisted of identifying and resolving the problems associated with their use to elucidate microbial processes in heterogeneous soils and sediments. Significant progress has been achieved in this respect, for example in the development of objective (operator-independent), local segmentation techniques adapted for X-ray μCT images [e.g., (Schlüter et al., 2010; Hapca et al., 2013; Houston et al., 2013a,b)], in terms of improvements of hybridization (FISH) technologies to locate bacterial and archaeal cells in soil thin sections (Eickhorst and Tippkötter, 2008; Schmidt et al., 2012), or in the in elaboration of statistical tools to interpolate 2-D measurements to produce 3-D data (Hapca et al., 2011, 2015). Shortly before the Research Topic on “Elucidating microbial processes in soils and sediments” was launched in August 2017, we felt that the time had come to switch to a higher gear, more focused on interdisciplinarity, in the research in this area, and we were convinced that encouraging our colleagues to submit jointly a number of manuscripts describing their work on this topic was the best approach to pave the way for this switch to occur. As part of the Research Topic, it was decided that a comprehensive review article would be put together, covering as much as possible of the relevant literature, and trying to identify major axes, or “paths,” in it. In the resulting article (Baveye et al.), we identify three major disciplinary paths along which research efforts have taken place in the last 15 years, and which, when they will eventually converge in full interdisciplinary mode, should provide a far better grasp than what is currently available of what controls the activity of microorganisms in soils. The key take-home message of Baveye et al.'s review, visualized in Figure 1, is that significant progress has been achieved on a number of fronts, but that progress unfortunately is very uneven. At the extremes of the spectrum are the research on the physical characteristics of soils at the microscale and the (arguably more complicated) experimental observation of microbial processes. While the former has moved full speed ahead, the latter has been lagging far behind, casting doubt on the soundness of some of the modeling that has been carried out in this field, and hindering the needed integration of physical, (bio)chemical, and microbiological perspectives. Clearly, the picture that emerges from the extensive literature covered in Baveye et al.'s review suggests that, as of 2018, there was still a long way to go before reaching the Holy Grail, with many daunting challenges on the different paths leading to it. Figure 1. Visual assessment of the level of progress along various paths in the research on the emergent properties of microbial activity in heterogeneous soil microenvironments. The colored parts correspond to Baveye et al.'s estimate of the progress achieved to date along each path. The shaded portions of the diagram still largely remain to be tackled. In more ways than one, the various articles published as part of our Research Topic have managed, if not to reach the Holy Grail (that may have been a bit much to hope for), at least to address some of the challenges head on, and to make significant progress concerning quite a few of them. A first group of articles focuses on the characterization of the geometry of the pore space, in which all the (bio)chemical and microbial processes take place in soils, and deepens our understanding of how this geometry as well as the architecture of the solid phase influence, or are symptomatic of, soil behavior. San José Martinez et al. explore the ability of Minkowski functionals of the connected soil pore space to discriminate between the pore geometries exhibited by soils with different managements and depths, and that are therefore expected a priori to be dissimilar. The crucial question of how well microscale measurements carried out via X-ray microtomography can help us unravel the relationship between microscopic soil architecture and macroscopic soil properties is addressed by Smet et al. These authors deal in particular with practical questions associated with the implementation of X-ray computed microtomography, including how well the samples represent the uniqueness of the pore network or architecture, and the systemic compromise between sample size and resolution. A second group of four articles deals with the “hot” topic of the distribution and fate of soil organic matter (SOM). Maenhout et al. are interested in the impact of soil structure on N availability to microbes, and thus on heterotrophic microbial activity and community structure. Their results with artificially reconstructed miniature soil cores with contrasting soil structures, viz. high or low degree of contact between soil particles ascertained via X-ray μCT, suggest that soil structure controls carbon mineralization through mediation of N diffusion and in turn N availability. Working with aggregates from a California forest and a Nevada shrubland soil subjected to different soil moisture and “heating” regimes, Jian et al. show that low-severity fires can accelerate the decomposition of soil organic carbon (SOC) protected in soil aggregates. Quigley et al. try to characterize the spatial heterogeneity of the soil matrix in macroaggregates obtained from soils associated with three contrasting long-term managements (conventionally-managed and biologically-based row-crop agricultural systems, along with a primary successional unmanaged system), and they explore the usefulness of grayscale gradients as proxies to determine the microscale spatial distribution of soil organic matter (SOM). Finally, Quigley et al. use the natural difference between carbon isotopes of C3 and C4 plants to determine how the presence of pores of different sizes affects spatial distribution patterns of newly added carbon immediately after plant termination and then after 1-month incubation. The results indicate that, in the studied soil, pores of 40–90 μm size range are associated with the fast influx of new C followed by its quick decomposition, whereas pores <40 μm tend to be associated with C protection. The next group of articles deal with microscale aspects of soils related to the presence of plant roots. van Veelen et al. use correlative X-ray CT (resolution ~20 μm) in combination with Magnetic Resonance Imaging (MRI, resolution ~120 μm) to set up groundwork to enable in situ visualization of root-produced mucilage in soil. Benard et al. also focus their attention on this mucilage. They use a percolation approach to predict the flow behavior in the rhizosphere near the critical mucilage content. At that particular stage, a sufficient fraction of pores is blocked and the rhizosphere turns water repellent. Two other articles deal with the influence that plant roots, by themselves or through chemicals they exude, can have on microorganisms in their vicinity. Rodeghiero et al. combine planar optodes and spatial analysis to assess how tomato roots influence the metabolic activity and growth patterns of the fungus Fusarium oxysporum f. sp. lycopersici (Fol), one of the most destructive soil-borne diseases of tomatoes. Using fluorescence microscopy combined with automated image analysis and spatial statistics, Schmidt et al. carry out a gnotobiotic experiment using a potential nitrogen-fixing bacterial strain in combination with roots of wetland rice to explore the distribution of bacterial colonization patterns on rhizoplanes of the rice roots. Another group of articles in this Research Topic deals with observations of the distribution and dynamics of microorganisms in soils. Chamizo et al. inoculated two cyanobacterial species, Phormidium ambiguum (non N-fixing) and Scytonema javanicum (N-fixing) on different textured soils (from silt loam to sandy), and used scanning electron microscopy to analyze the development of cyanobacteria biocrust and the evolution of selected physicochemical properties of the soils for 3 months under laboratory conditions. Couradeau et al. also worked on biocrusts. They developed methodologies to visualize and quantify the water dynamics within an undisturbed biocrust undergoing desiccation. In particular, using synchrotron-based X-ray microtomography, they were able to resolve the distribution of air, liquid water, mineral particles and cyanobacterial bundles at the microscale. Vermeire et al. assess the reciprocal interactions between soil minerals, SOM, and the broad composition of microbial populations in a 530-year chronosequence of podzolic soils. Choi et al. use a metagenomic sequencing method to assess the distribution of genes encoding for key cellulose-degrading enzymes among aggregate fractions in a fertilized prairie soil. Watteau and Villemin. illustrate with studies involving a variety of soils in different contexts (i.e., five cropped soils, one forest soil, and one Technosol) that Transmission Electron Microscopy (TEM) can be used advantageously to localize microorganisms and deduce their influence within soil structures. In particular, organic matter turnover can be assessed within microhabitats through a combination of TEM, Electron Energy Loss Spectroscopy (EELS) or NanoSIMS. Finally, Juyal et al. address the extent to which it is possible to control the pore geometry at microscopic scales in microcosms made of repacked aggregates, through manipulation of common variables such as density and aggregate size. In addition, they analyze in these microcosms the effect of pore geometry on the growth and spread dynamics of Pseudomonas sp. and Bacillus sp. bacteria following their introduction into soil. The next group of articles focuses on the use of artificial media to gain a better understanding of the factors that control the distribution and activity of microorganisms in pores. Schlüter et al. introduce an experimental framework relying on simplified porous media (consisting of aggregates of porous, sintered glass beads) that circumvents some of the complexities occurring in natural soils while fully accounting for physical constraints believed to control microbial activity in general, and denitrification in particular. They use this framework to explore the impact of aggregate size and external oxygen concentration on the kinetics of O2 consumption, as well as CO2 and N2O production. Guo et al. are interested in how the pore geometry of a soil can affect the extent to which bacteria are able to influence local moisture conditions through the secretion of extracellular polymeric substances (EPS). They systematically measured the rate and extent of water evaporation from pore structures as a function of both EPS concentration and pore size. They used for that purpose three different types of two-dimensional chambers: glass capillary tubes with a uniform macropore geometry, emulated soil micromodels representing an aggregated sandy loam pore geometry, and microfluidic capillary arrays to represent a uniform micropore geometry. Using the same type of micromodel of a sandy loam soil, Soufan et al. try to ascertain that the fungus Rhizoctonia solani can indeed grow in such an environment, and then to identify and analyze in detail the pattern by which it spreads in the tortuous pores of the micromodel. Finally, a last group of articles uses theoretical calculations or computer modeling to describe processes that control the interaction of bacteria with pore surfaces, or the activity of bacteria in soils. Bradford et al. present a theoretical method to determine the mean interaction energy between a colloid and a solid-water-interface when both surfaces contain binary nanoscale roughness and chemical heterogeneity, and they illustrate the application of the method to bacterial retention on solid surfaces. Portell et al. explore in silico the hypothesis that the heterogeneous distribution of soil organic matter, in addition to the spatial connectivity of the soil moisture, might account for the observed microbial biodiversity in soils. The analysis rests on a multi-species, individual-based, pore-scale model that is parameterized with data from 3 Arthrobacter sp. strains, known to be, respectively, competitive, versatile, and poorly competitive. One may wonder to what extent all these 22 manuscripts, published over the last year, have managed to put some color in the schematic diagram of Figure 1, i.e., dissipate a little bit the knowledge gap that existed on many questions at the time the graph was established. We lack the necessary perspective to determine if the articles contained in this Research Topic will contribute to make a serious dent in the gray zones of Figure 1, but it is comforting in this context to see that quite a few articles, either through experiments or modeling, deal head on with the challenges associated with the distribution and activity of microorganisms in soils at the microscale. As mentioned earlier and as illustrated by Baveye et al. in Figure 1, microscale research on the microbial components of soil systems until recently has been seriously lagging behind the work on the physical and (bio)chemical characteristics. It is encouraging to see, among the various articles gathered in this Research Topic, several resolutely engage along this relatively unexplored path. Arguably as a result of the Research Topic, or at least stimulated by it, the research on the microscale properties of soils is now entering into another phase, where different techniques and disciplinary outlooks will be systematically combined to apprehend more completely the characteristics of microhabitats in terrestrial systems. A number of research groups around the world are now trying to quantify the physical and (bio)chemical features of these microhabitats, as well as to describe as thoroughly as possible the composition and biodiversity of microbial populations they contain. The very recent article by Schlüter et al. (2019) is an excellent example of the type of work that is unfolding in this area. Using a combination of X-ray μCT, fluorescence microscopy, scanning electron microscopy and nanoSIMS, these authors are able to study the distribution of bacteria in a soil, and to show that they have a preference toward foraging near macropore surfaces and near fresh particulate organic matter. Juyal et al. (2019) combined X-ray CT with biological thin sections to elucidate the impact of pore architecture on bacterial distribution in soil. They highlighted that when different methods are being integrated, one needs to consider an “appropriate spatial scale” to understand the factors that regulate the distribution of microbial communities in soils. It is hoped that these type of interdisciplinary efforts will not only help us understand better what controls the activity of microorganisms in soils, but will also enable us to (finally) make progress on the intimately linked topic of the dynamics of humic substances (e.g., Baveye and Wander, 2019). We feel confident that within the next few years an increasing focus will be placed on integration of techniques. Progress in this respect will likely be fueled very significantly by the development of an array of new techniques, e.g., single-cell metabolomics or X-rays produced by plasma wave accelerators, which offer great promise for the research on soils and sediments. It may take a significant time, still, to develop the type of macroscopic descriptors of the emergent properties of microbial activity that are all the way in the gray zone in Figure 1, and that we desperately need to predict how soils are likely to react to the changes we impose on them, but at least we now seem to be on track to 1 day get there. This brief description of the salient aspects of the Research Topic on “Elucidating microbial processes in soils and sediments” would not be complete without mentioning an event that took place in June 2018 and, although distinct from the Research Topic per se, was nonetheless intimately connected with it. A workshop, entitled MicroSoil 2018, was organized in the château of Saint Loup Lamairé (Deux Sèvres, France) in part to allow a sizeable number of authors of articles published in this Research Topic to get together and interact. A group of 50 researchers from 7 different countries gathered for 3 days (Figure 2), and actively debated about the status of the research, about impediments to its necessarily interdisciplinary character, and about plans for future research activities. A very positive outcome of the workshop is that several researchers from different institutions have decided to collaborate on joint projects (e.g., Vidal et al., 2019). A follow-up MicroSoil Summer school will take place in June 2019, again in Saint Loup Lamairé, and another workshop, MicroSoil 2020, similar to the 2018 one, will be held there in June 2020. Figure 2. Group picture of the attendees of the Microsoil 2018 workshop, held in the château of Saint Loup Lamairé (Deux Sèvres, France) in June 2018. The group comprised 50 researchers from 7 countries, who for 3 days, debated issues associated with the Research Topic in a very relaxed atmosphere. All authors listed have made a substantial, direct and intellectual contribution to the work, and approved it for publication. The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Alexander, M. (1964). Biochemical ecology of soil microorganisms. Annu. Rev. Microbiol. 18, 217–250. doi: 10.1146/annurev.mi.18.100164.001245 PubMed Abstract | CrossRef Full Text | Google Scholar Baveye, P. 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W., Nguyen Tu, T.-T., Buegger, F., et al. (2019). Earthworm cast formation and development: a shift from plant litter to mineral associated organic matter Front. Environ. Sci. 7:55. doi: 10.3389/fenvs.2019.00055 CrossRef Full Text | Google Scholar Keywords: microbial ecology, carbon sequestration, soil organic matter, greenhouse gas production, dynamics, modeling Citation: Baveye PC, Otten W and Kravchenko A (2019) Editorial: Elucidating Microbial Processes in Soils and Sediments: Microscale Measurements and Modeling. Front. Environ. Sci. 7:78. doi: 10.3389/fenvs.2019.00078 Received: 02 May 2019; Accepted: 20 May 2019; Published: 07 June 2019. Edited and reviewed by: Denis Angers, Agriculture and Agri-Food Canada (AAFC), Canada Copyright © 2019 Baveye, Otten and Kravchenko. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. *Correspondence: Philippe C. Baveye, [email protected]
Published: 25 September 2018
Frontiers in Aging Neuroscience, Volume 10;

Editorial on the Research TopicMood and Cognition in Old Age Depression and cognitive impairment are great challenges for the elderly population. The Research Topic “Mood and Cognition” by Frontiers in Aging Neurosciences comprises 16 articles addressing new findings and perspectives concerning mood and cognition in old age, including age-related disorders (e.g., elderly depression, mild cognitive impairment, and Alzheimer's disease). The articles presented focus on the role of the brain structure and activity in mood and cognition and explore several hypotheses regarding their association with new pathophysiological processes such as inflammation, the association with other comorbidities, as well as the impact of invasive medical procedures on cognition and delirium. Other approaches are focused on the influence of socialization, interpersonal relations, and social learning on cognitive performance and quality of life. Three articles are focused on the connection between dementia (Alzheimer's Disease-AD) and depression. Liu et al., conducted a study explaining how the hypothalamus interacts with other brain regions in AD patients with depression (D-AD), using a functional connectivity (FC) analysis. This promising study showed that D-AD patients had reduced FC in the hypothalamus, the right middle temporal gyrus and the right superior temporal gyrus compared with the FC of nD-AD patients, and suggested that the abnormal FC between the hypothalamus and the temporal lobe may play a key role in the pathophysiology of depression in AD patients. Lebedeva et al., assessed whether structural brain magnetic resonance imaging (MRI) in late-life depressed patients (LLD) could predict mild cognitive impairment or dementia 1 year prior to the diagnosis. The authors concluded that the analysis of the baseline structural MRI alone was able to accurately distinguish LLD patients developing MCI and dementia, from those remaining cognitively stable. Moreover, the authors showed that the ventral diencephalon, including the hypothalamus, might play an important role in the preservation of cognitive functions in LLD. Following the same line, Liu et al. investigated the relationship among a history of depression, depressive states, and dementia in a community-based old-old cohort in Japan. This valuable study concluded that a history of depression should be considered a risk factor for all-cause dementia and that, in the old-old population, depression was associated with a higher prevalence of dementia, lower cognitive performance, and a smaller hippocampus. The study of Hou et al. examined the implicit relationship between the disruption of interhemispheric functional coordination and cognitive impairment in late-onset depression (LOD), using functional magnetic resonance imaging (fMRI). The authors state that the altered linkage patterns of intrinsic homotopic connectivity and impaired cognitive flexibility may constitute a novel clue regarding the neural substrates underlying cognitive impairment in LOD. Zhao et al. present a hypothesis and theory article focusing on post-stroke depression (PSD), which is a common neuropsychiatric complication in patients who have suffered a stroke. The authors explored the inflammation hypothesis for PSD and point to preventive and therapeutic strategies, specifically remote ischemic conditioning (RIC). They concluded that RIC may be a novel approach to prevent PSD, with potential to be widely used in clinical practice and to be applied in other neurobehavioral disorders. Moretti and Signori conducted a very interesting review regarding the neural correlates for apathy in frontal-prefrontal and parietal cortical-subcortical circuits. In spite of the controversial definitions, with different categorizations of this nosographical entity, the present discussion may contribute to new insights about apathy in the context of several pathologies being degenerative, vascular, acute, or chronic. The authors concluded by highlighting important future directions toward goal-specific problems. In their article Gamaldo et al. examine the rates, predictors, and outcomes of sleep disturbances in older hospitalized patients. This is the first study to use a large national (USA) healthcare database, with 35,258,031 of older adults. Stating that the proportion of older adults with a sleep diagnosis has increased significantly over the last decade, this study documented an important association between increasing sleep disturbance rates and expenditures within hospital settings. Moreover, co-morbidities such as depression, cardiovascular risk factors, and neurological disorders steadily increased over time in these patients. Also from the USA, Assari and Lankarani conducted a study focused on the reciprocal and longitudinal associations between depressive symptoms and mastery, comparing black and white American older adults. They found that, among white but not black older adults, higher levels of depressive symptoms at baseline predicted a greater decline in sense of mastery over 3 years' follow-up, stating that race may alter how depression is linked to changes in evaluation of self (e.g., mastery) over time. Focusing on cognition, the article of Palaci et al. explored how parental economic socialization affects the planning for retirement (FPR) through the mediation of financial literacy, financial planning decisions, and financial management. The results show that parental economic socialization directly and indirectly influences FPR, and that parental economic behavior acts as a positive model for the development of financial literacy and skills and for decisions about FPR. Based on this, the authors point out important future lines of research. Ouanes et al. conducted a population-based study, hypothesizing that increased cortisol may be associated with poorer cognition and with certain personality traits (mainly high neuroticism), and that personality might explain the association between cortisol and cognition. This study found that high agreeableness and openness might be associated with poorer executive performance in later life. Moreover, increased cortisol may be associated with both specific personality traits (high extraversion, low openness) and worse cognitive performance. In spite of this, the authors concluded that the association between personality traits and cognitive impairment seems to be independent of increased cortisol production and its effects on cognition. Two articles are specifically dedicated to Alzheimer Disease (AD). The article from Wang et al. explored the interaction dynamics between different electroencephalographic (EEG) oscillations in AD patients, comparing the resting eye-closed EEG signals in AD patients and healthy volunteers. The authors propose that the pathological increase of ongoing gamma-band power might result from the disruption of the GABAergic interneuron network in AD patients. They also suggest that the cross-frequency overcouplings, might indicate the attenuated complexity of the neuronal network, and that AD patients have to use more neural resources to maintain the resting brain state. These promising findings provide new evidence of the disturbance of the brain oscillation network in AD and further deepen the understanding of the central mechanisms of AD. Focused on the genetics of the disease, Lukiw et al. provide recent evidence for the mis-regulation of a small family of genes expressed in the human hippocampus that appear to be significantly involved in the expression patterns common to both AD and aggression. The magnitude of genes expression implicated in aggressive behavior appears to be more pronounced in the later stages of AD when compared to MCI. These recent genetic data further indicate that the extent of cognitive impairment may have some bearing on the degree of aggression which accompanies the AD phenotype. Two other important articles focused on delirium. El-Gabalawy et al. developed a novel stress-diathesis model based on comprehensive pre-operative psychiatric and neuropsychological testing, a blood oxygenation level-dependent (BOLD) magnetic resonance imaging (MRI) carbon dioxide (CO2) stress test, and high fidelity measures of intra-operative parameters that may interact facilitating post-operative delirium (POD). Results provide preliminary support for the interacting of diatheses (vulnerabilities) and intra-operative stressors on the POD phenotype. Based on these initial findings, the authors offer some recommendations for intra-operative management for patients at risk of POD. The article from Dong et al. presents the results of a clinical investigation on the associations between the preoperative expression levels of microRNA (miR)-146a, miR-125b, and miR-181c in cerebrospinal fluid (CSF) and serum and the development and severity of post-operative delirium (POD). It found that dysregulation of preoperative miR-146a and miR-181c in CSF and serum was associated with the development and severity of POD, and that these NeurimmiRs might participate in the neuropathogenesis of POD. Also exploring cognitive changes after invasive medical procedures, Kulason et al. present preliminary results of a pilot study, being the first report to examine Postoperative Cognitive Decline (POCD) after major thoracic surgery (partial pulmonary lobectomy lung) in elderly Japanese patients. This pioneer study clarified that decline in cognition is detectable to a certain extent after the surgery. Additionally, longer anesthetic exposure may negatively impact on attention and working memory, and preoperative mental well-being is a possible predictor of POCD. Cleutjens et al. investigated whether macrostructural brain MRI features of cerebral small vessel disease (SVD) and hippocampal volume (HCV) are related to cognitive performance in patients with chronic obstructive pulmonary disease (COPD). No group differences were reported, regarding demographics, clinical characteristics, comorbidities and the presence of SVD features and HCV. This way, the authors concluded that there is not yet evidence for a relationship between cerebral SVD and HCV and cognitive functioning in patients with COPD and that additional studies will be needed to determine other possible mechanisms of cognitive impairment in these patients. In all, this Research Topic may contribute to building different perspectives on how mood and cognition in late life could be influenced by the brain structure, activity and aging, and how this may interact with environmental stimuli and interpersonal relationships. All these studies would enrich our understanding of the bio-psycho-social mechanisms underlying improving psychological well-being and cognitive health. All authors listed have made a substantial, direct and intellectual contribution to the work, and approved it for publication. The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. HW received support from the National Research and Development Project of Ministry of Science and Technology (2017YFC1311100). Keywords: mood disorder, mild cognitive impairment, Alzheimer's disease, neuroimaging, psychology Citation: Fernandes L and Wang H (2018) Editorial: Mood and Cognition in Old Age. Front. Aging Neurosci. 10:286. doi: 10.3389/fnagi.2018.00286 Received: 20 July 2018; Accepted: 03 September 2018; Published: 25 September 2018. Edited and reviewed by: Thomas Wisniewski, New York University, United States Copyright © 2018 Fernandes and Wang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. *Correspondence: Huali Wang, [email protected]
Chih-Hui Lai
Published: 1 March 2007
Journal: M/c Journal
M/c Journal, Volume 10;

Exhausted after a working day, a fatigued New Yorker may be desperate to find a place to relax and meet friends. With the help of Dodgeball and a series of text messages back and forth on his mobile phone, he immediately knows that two of his buddies are in a pub three blocks away from his office. Across the Pacific Ocean, in Tokyo, Japan, a group of twenty-something girls may be also exploiting the similar service, ImaHima, to check out their friends’ location, activity and mood while they are arranging a spontaneous meeting on their way out. In Taiwan, a large number of mobile users, young and old, are involved in EzMoBo’s EzDating and EzFriend to express themselves and make acquaintances via texts, pictures and video clips. Aggregately, this is how the emerging mobile social networking service works. Given the relative youth of mobile social networking, and the fact that few extant studies are dedicated to this subject, a case study of exploratory nature is deemed a preferred approach in order to understand its use. There are several reasons explaining the selection of the Taiwanese case-EzMoBo. In terms of evidence, Taiwan’s mobile penetration rate was 97.37% in 2005 and the SMS volume reached 2,796 million in the same year (“Penetration Rate” 1; “SMS Volume” 1). In addition, 36.4% of all Taiwanese mobile phone users have used the mobile phone for non-voice services, such as Wireless Application Protocol (WAP), General Packet Radio Services (GPRS) and SMS (“Proportion in the Number” 1). These figures generally represent mature mobile culture in Taiwan. In other words, the mobile use in Taiwan has played a role in human communication in various aspects. This fact makes Taiwan a perfect social setting to observe the adoption of mobile social networking and extrapolate it to the explanation of similar cases in other cultural contexts. Particularly, EzMoBo was selected due to its large user base of 400,000 as well as its relatively developed mobile social network application since 2001. As the enquiry unfolds, four major components are found to be associated with the use of mobile social networking, which are Taiwanese cultural contexts, personalized mobile communication, the formation of unique mobile community and the value of visual content and texting. When it comes to the adoption of a new communication technology, a connection should be made to users’ existing and typical media uses. In Taiwan, media culture is characteristic of highly popular uses of mobile phones, BBS (bulletin board system) and online gaming. Through contextualization of these three aspects of Taiwanese media uses, a better understanding of EzMoMo’s design can be achieved. It is also reasonable that, due to this consideration, the local contextual associations occupy a relatively large portion of the analyses. Meanwhile, in order to provide explanations of this observation, a number of academic studies are referred to. First, Barry Wellman’s study of cyberspace has provided insights into the effects of mobile communication and subsequent social changes (“Physical Place” 227). Among several aspects he mentioned, two of which, wireless portability and personalization of technology, are germane to the topic of interest in this paper. Considering the important feature that mobile social networking serves to enable people to manage community on the go based on their common interest, therefore, the third part of the analysis is focused on the formation of mobile community. The investigation will include the characteristics of the mobile community and its relation to the design principle as well as cultural factors. Lastly, in the technical aspect, the role of Short Messaging Service (SMS, or text messaging) and Multimedia Messaging Services (MMS) is discussed regarding their functional and symbolic contribution in achieving human interactions. SMS is the main technical standard of text message transmission between mobile devices whereas MMS is the upgraded version of SMS by incorporating image, video, picture and other forms of messages. The data is obtained from a semi-structured interview with Irene Liu, senior project manager of EzMoBo, as well as from the relevant documents provided by EzMoBo. As the first inter-operator mobile community service, EzMoBo started business in September 2002 and positioned itself as a content platform provider. Featuring various forms of mobile community services, such as social networking, mobile online games and picture/video albums, EzMobo’s most popular services, EzFriend and EzDating, are considered to be composite mobile communities. Applying multiple interfaces, such as SMS, MMS, location-based service (LBS), Wireless Application Protocol (WAP), avatar and RPG, EzFriend and EzDating make good use of user-centered contributions in various forms. In other words, without directly providing contents, EzFriend and EzDating relied on users to generate the content and share it among the entire community. For example, users can participate in writing entries in the blog area, posting messages in BBS, joining chat rooms, and communicating with personalized pictures and video clips. EzFriend, launched in September 2002, is EzMoBo’s first generation of mobile community service. Compared with less sophisticated EzFriend, EzMoBo later introduced the second generation mobile community-EzDating, which incorporates the concept of role-playing game (RPG) and avatar. According to EzMobo’s estimate, the user base of these two community services has reached 400,000 as of July 2006, which crowns EzMoBo’s success as the largest mobile community service in Taiwan. Furthermore, its service map has expanded to China and Singapore in 2005 and 2006, respectively. Similar to web-based instant messaging, in EzFriend and EzDating, once users are logging into the portal, their online status will be updated. The only difference is that this mobile community is a public discussion forum without a separate conversation window for the pair-based discussion, as in the web-based instant messaging. In terms of community interface, as shown in Figure 1, each user is generally presented with their nickname, mood status, the number of e-coins, their level (EzDating), the number of online users and online friends, and the number of new messages. The level, ranging from one to twenty, represents the overall evaluation of one’s appeal index and force index (see Figure 2). For example, if users receive a mail, they will be able to gain ten points. If they use real-world money to purchase accessories for the avatar, their appeal index will increase by 300-1000 points. According to EzMoBo, the presentation of one’s level is an incentive for users to be more actively involved in various mobile community activities, including sending and receiving messages, creating a message board, initiating a vote topic and sending a gift. For instance, every time one’s picture is downloaded by other users, they will get 10 e-coins. Alternatively, this mechanism encourages users to make efforts to strengthen their currency stock as well as monitoring other users’ level. There are some cases that users complained to EzMoBo about other users’ abnormal level presentation and the number of virtual currency revealed. Investigating further, EzMoBo’s large user base is ascribed to its creation of a competitive and playful environment, which encourages users to vie with each other to accumulate virtual currency and use it to exhibit one’s appeal and force ranking as well as purchase virtual gifts. For example, users can spend virtual currency they earn on staging a promotion show. In the case of EzDating, there is evidence showing that many users tend to user real-world money to purchase expensive avatar accessories and send them as virtual gifts to their friends. The recipients then will get a MMS notification, which inquires them whether to wear the new accessories received. If the recipients deem the new gift redundant, they could pawn it to get virtual currency in return. This mechanism has delicately rendered the separation of the virtual world and the real world indistinguishable. It is not surprising to find that users are accustomed to the use of virtual currency as part of gift exchanges, especially on the occasion of making new friends and making impression on people they admire. In the aspect of user demographics, the users cover a wide range of ages, from 15-year-olds to 70-year-olds. Those 21-30 years of age are the major user group, followed by those ages 31-40. Approximately, 38.8% of EzFriend users and 20.1% of EzDating users are 21-30 years of age while those ages 31-40 occupy 12.8% and 6% of these two services, respectively. Nonetheless, those in their 60s or 70s are found to be the highly loyal users of these two services. In terms of gender differences, males dominate the usage with the ratio of six to four, as compared with the female users. Geographically, the usage of these two mobile community services is still ahead in the northern metropolitan areas, with roughly 35% of users concentrating in Taipei and other northern developed cities. Lastly, another aspect concerning user category is intriguing. According to EzMoBo’s investigation, army officers, janitors, and 24-hour open convenient store clerks are the chief members of these two mobile communities. Interestingly, the use of mobile social networking could be better understood by explaining its association with three prevalent cultural practices in Taiwan, which are mobile phones, BBS and online gaming. First, the importance of mobile phones in daily life of Taiwanese people is manifested in several aspects. Wei and Lo’s study on Taiwanese college students revealed that mobile phones have replaced the traditional means of maintaining family bonds and significant relationships (68). In a broader sense, sharing similar national culture background and the Confucian tradition, the use of mobile phones in Taiwan, China, Japan, and Korea are somewhat tinted with entertainment (Ishii and Wu 96). In Taiwan, diverse uses of mobile phones for entertaining purposes are common. For example, college students use mobile phones mainly to chat with their close friends about mundane things (Lin, Cheng and Lin; Cheng). According to a survey conducted by the official research institute FIND in 2005, almost 40 percent of Internet users used their mobile handsets for Internet activities and 35 percent of these uses occurred on public transport, waiting queues or any idle time. SMS, screen graphics and ring tone downloading, mobile games, and MMS were the top popular five applications (“Taiwan Mobile Internet Survey 2004”). What renders these applications popular is attributed to their interactivity, customization and entertaining features. Taken together, these descriptions point out Taiwanese people’s tendency of accepting diverse and entertainment-oriented mobile applications. Secondly, the unique element of Taiwanese Internet culture, BBS, is found to mesh well with user practices employed in EzFriend and EzDating. The Telnet-based BBS incorporates multiple functions that have been applied in the web-based instant messenger and online games. Once users register, they are able to create a plain profile and nickname for their identity. Then, they can post messages, participate in a wide range of topical discussions, talk with friends, exchange emails and initiate a vote topic. Evidently, these practices derived from BBS are observable in the use of EzFriend and EzDating. Moreover, in well-established BBS, board masters are required for establishing board rules and maintaining order among the virtual BBS community. In EzFriend and EzDating, similar mechanism is also present, which helps create a coherent spirit among the mobile community. More advanced BBS has already introduced online games and the trade mechanism of exchanging virtual treasure and token (Ishii and Wu 100). Through pure textual communication, BBS users pay attention to their e-signatures and writing styles in order to exhibit their personal characteristics. The influence of BBS on Taiwanese society is notable in that it has become a subculture among the Taiwanese Internet world (Ishii and Wu 100; Hsueh; Fu and Wang). The third parallel social factor is related to Taiwanese online gaming culture, which has evolved with the use of mobile phones and BBS. In Taiwan, teenagers are generally constrained by the social rules of pursuing academic achievements. Playing online games with a few friends in a cyber café thus becomes an identifiable vehicle for relaxing (Ishii and Wu 101; Huang; Chai). This background explains why various forms of electronic games easily garnered notable popularity among Taiwanese young people. Particularly, the younger Taiwanese generation is found to have been growing with online games, which are alternatively viewed as a subculture among teenagers (Chen; Pan). In fact, propelled by the high penetration rate of broadband Internet, online game playing becomes the dominant activities among Taiwanese Internet users across all age brackets, with the youngest age group of five (Pan). According to the latest survey on a national scale, 64 % of the Internet population is involved in online games, with students and 15-19 year-olds as the major users (Y. Lin). In the same survey, it identifies that role-playing is the most popular online game categories, followed by action and strategy. Role playing games enable users not only to exercise creative learning but also to make friends and find partners to cooperate and connect with (“From PC to Mobile Phones, Avatar Enables Friend-Making”). Among the various mechanism of role-playing gaming, avatar has been widely used, whether in Internet forums or online games. Avatar is the digitalized representation of individuals and is usually denoting the “paper doll” game mechanism (J. Lin). With the aid of avatar, users are exposed themselves to a more intimate environment and are able to express themselves as well as communicate with other people. The popularity of avatar in Taiwan is basically rooted in Korea, where avatar is the equivalent of email communication. Wayi, an online game developer in Taiwan, partnered with Koreas developers and introduced “Noritel” in Taiwan, which won over 50,000 users within two months of its introduction in July 2003. The inclusion of avatar is well accepted among the Taiwanese online game population as well as the mobile phone users. Taiwan Mobile and FarEas Tone both provided a mobile social networking service called “e7Play Love City,” enabling mobile users to participate in the process of making friends through decorating avatars and personal rooms (e7Play Love City). Another mobile social networking service, Pet Sweety, offered by Taiwan Mobile, FarEas Tone and Chunghwa Telecom, has similar functionalities. These are only two of a number of examples of avatar-embedded mobile applications in Taiwan. In general, within this local context of online gaming culture, the successful adoption of EzFriend and EzDating can be linked to its integration of role-playing games, virtual currency and avatar mechanisms since Taiwanese consumers have familiarized themselves well with these online games practices over time. Nonetheless, it is still too early to conclude whether there is any overlapping or migration occurring between the online game and the mobile social networking population. According to the foregoing analysis, a majority of online gamers are under the age of 15. In Taiwan, those target groups of teenagers and children are not allowed to purchase mobile phones themselves and thus, they are more likely to use pre-paid cards or financed by their parents. Drawing upon this fact, obviously, either the pre-paid mechanism or the parental control is a barrier of using advanced mobile applications since young users are more inclined to spare the limited minutes for voice communication. Conceivably, in this phase, it is appropriate to state that the feature of online gaming is only one of the many incentives offered to use mobile social networking. Another two contextual factors, the highly penetrated mobile usage and mature development of BBS should also account for the popularity of EzFriend and EzDating. Mobile technologies, from mobile phones to text messaging, have transformed interpersonal connections, which are independent from the fixed location, and have resulted in the phenomenon of “situated nowhere,” in which communication occurs everywhere (Wellman, “Physical Place” 230). The ubiquitous form of communication allows people to micro-coordinate activities without prearranging an agreed-upon time and space (Ling and Yttri 2). This consideration of ubiquity is evidenced by the characteristics of the main user groups of EzFriend and EzDating. According to EzMoBo’s survey, the major users, such as soldiers and convenient store clerks, are characterized by having inadequate access to PC and web-based social networking. Thus they are attracted by the anytime-anywhere wireless capability enabled by mobile social networking. In addition to the wireless aspect, the personalization of technologies plays a role in influencing the way people interact with each other. Specifically, the use of personalized software, such as setting the preference for matching persons nearby and limiting the number of recipients to receive message, is therefore shifting community ties from “linking people-in-places” to “linking people where they are,” or namely personal communities (Wellman, “Physical Place” 238). The emphasis on personalized communication is reflected in the multi-interface design of EzFriend and EzDating, which incorporates multiple modalities of communication, such as verbal communication through voice and text messaging, and non-verbal communication by way of picture and video messaging. Furthermore, users of EzFriend and EzDating are armed with the capability of managing their contextual information through the modification of availability status and of optimizing their competitive advantage through the accumulation of virtual currency. Particularly, the user-generation content is considered as another solution to intertwine the mobile technology with human need to express themselves and communicate with each other. This nicely explains EzFriend and EzDating’s dependence on user-generated content. Whether using it for moblogging, communicating with a large group of community members or uploading personalized picture profiles or video clips, users have relatively more freedom to make use of mobile social networking as a benefit. Technically, mobile instant messaging, text messaging, voice communication, moblogging, and photo messaging are the available means serving community members’ various needs. In a broad sense, mobile social networking can be defined in parallel with the mobile community. Rheingold defined that the mobile virtual community is characterized by blending the features of virtual communities and mobile communication, which are characteristic of affinity-based and local-acquaintance-based social communication (“Mobile Virtual Community”). More specifically, mobile virtual communities are known as a platform for many-to-many communication, a platform for coordinating activities in geographic space, and an arena for gaming and socializing. In the case of EzFriend and EzDating, groups were formed in a spontaneous manner through the cooperation of a few initiators. For example, a group of users once initiated a roll call to encourage its group members to cling to the service, according to EzMobo’s observation. In addition, by incorporating various forms of user-generated content, such as BBS and the decoration of the avatar, the group formation in EzFriend and EzDating makes good use of the value of chat messages. According to Taylor and Harper, the value of chat message lies in its ability to help people establish chat groups, which serves to cement alliances with groups and sustain a sense of place in a virtual space (294). In general, reflecting upon these characters of mobile community, a discernible fact is detected as to the difference between mobile-enabled community and mobile community. The former refers to the conventional social networks communicating with each other using mobile phones whereas the latter focuses on the interest-based virtual group mediated through mobile phones. Similar to online social networking, membership of a mobile community, for the most part, is built on the commonality, either expressing oneself or making friends. This observation corresponds to Rheingold’s delineation of mobile social networking. He envisioned that the mobile community, which combines user-controlled social network information, locative media, and mobile telephony, is expected to take shape as the way “virtual communities, online markets, and self-organized dating services emerged from wired cyberspace” (Rheingold, “Mobile Social Presence”). In addition to the forgoing BBS factor, the unique spending behavior among the users of EzFriend and EzDating helps to form coherence as a community. According to EzMoBo’s investigation, the users tend to expend a large amount of money on their participation. Unlike the web-based users accustomed to free service, these mobile community users naturally accept the payment mechanism for participation. For example, with the aim to court the admiring girls, some male users are eager to purchase expensive virtual gifts. On the design level, EzMoBo encourages users to be involved in various community activities, such as creating a message board or initiating a vote topic to increase virtual currency, which is viewed as an incentive for the formation of mobile community. In other words, the concept of community underlies the mechanism of EzFriend and EzDating. Technically, the main mechanism used across the platform of mobile social networking is messaging, including text, graphic, picture and video. In particular, most of the extant studies concern the influence of text messaging. There are two reasons explaining why the discussion of messaging is important. The first one is in relation to the functional orientations of text messaging. Compared with synchronous voice communication, asynchronous text messaging gives participants more control over the timing and content of their self-disclosures (Walther 199). Moreover, from the perspective of cultural consideration, it is agreed that text messaging is greatly assisting people that are reserved in expressing their feelings, such as Taiwanese people. Concurrently, another reason is concerned with the symbolic significance, in which messaging acts as a form of embodying memories and feelings that can be recalled through later readings (Colombo and Scifo 98; Taylor and Harper 275). Not merely an exchange of physical words or pictorial expression, the action of sending/receiving messaging itself also represents an offering of commitment to the relationship (Taylor and Harper 276; Thurlow). Correspondingly, this emotional significance is found in the multimedia message use of EzFriend and EzDating. It is obvious that the rich meaning enabled through MMS constitutes the main reason of the success of EzFriend and EzDating services. This attitude of adoption is also reflected in the user habit. The users of EzFriend and EzDating are characterized by adeptness of communicating with SMS and MMS. In addition, the embedded mechanism of gift-giving in EzFriend and EzDating can be associated with Johnsen’s discussion of digital gift-giving. In Johnsen’s argument, the gift in the form of text messages has been observed in playing a role in nurturing social ties and connections (166). In a more materialized manner, the gift performance in EzFriend and EzDating is observed in the exchange of multimedia messages as well as virtual gifts, such as flowers and avatar accessories. With multiple purposes, these gift exchanges allow users not only to manage their social relationships but also to increase their appeal and force index. Based on the case study of EzMoBo in Taiwan, four aspects of the use of mobile social networking are discussed, which are Taiwanese cultural contexts, personalized mobile communication, mobile community and mobile messaging. The uses of mobile phones, BBS and online gaming are prevalent in Taiwan society in the past two decades. Relevant users practices acquired through using these three communication technologies are found to extend to the utilization of mobile social networking. For instance, it is observable that the design of EzFriend and EzDating combines virtual currency, role-playing gaming and avatar mechanisms, which fit in with Taiwanese online gaming culture. The fact that users of EzFriend and EzDating are spontaneously forming group-oriented communication provides evidence of the orientation of community in human interaction, be it web-based, or mobile interface. Certainly, this is also related to the dominant user practices and community formation embedded in Taiwanese BBS culture. Finally, in terms of mobile messaging, EzFriend and EzDating are composite mobile social networking mediated through multimedia messaging. In addition to matchmaking, users are primarily counting on this forum to express themselves in text, picture and video forms. The value of visual content and text messaging finds its place in the realization of emotional connection and commitment to relationships. Since these innovative services are still in the early-adopted stage, related social issues and consequences might become more evident after they reach the full-adopted phase. Therefore, when that happens, the conclusion derived from the singular case study in Taiwan would be a starting point of analyzing mobile social networking in other cultural contexts, such as those in Japan, South Korea and the United States. It is needless to say that the support from further empirical research is necessary to provide an excellent complement to this exploratory study. In addition, some aspects pertaining to the development of location-based applications, such as emergency services, location-enabled advertising and travel guides, are subjects of interest for future studies. For instance, these topics would deal with cultural dimensions and their relationships with the usage patterns of these emerging services. By this way, the difference in the user interface would be rationalized using a more comprehensive perspective. Figure 1: EzFriend interface Figure 2: The avatar design in EzDating
Nwachukwu Ma
Published: 23 February 2018
Aspects in Mining & Mineral Science, Volume 1;

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Jiayong Liu, Chaoqian Zhao, Bin Liu, Hua Liu, Lixin Wang
Published: 10 May 2019
Journal: Oncology Letters
Oncology Letters, Volume 18, pp 771-775;

The curative effect and adverse reactions of pamidronate disodium in elderly patients with advanced metastatic bone cancer were evaluated. A total of 160 elderly patients with advanced metastatic bone cancer admitted to Affiliated Hospital of Nantong University from February 2012 to January 2015, were divided into the chemotherapy group (n=60) that received routine therapy and the pamidronate disodium group (n=100) that received pamidronate disodium therapy based on the chemotherapy. Pain relief, analgesic time, analgesic duration and side effects were compared between the two groups after treatment. The effect of pain relief in the pamidronate disodium group was significantly higher than that in the chemotherapy group (P Introduction Bone metastasis, a common complication of solid tumors such as advanced breast cancer, prostate cancer and lung cancer, has high incidence (1–3). Patients with advanced tumors suffer from bone pain and fracture due to the deterioration of tumors and bone metastases, causing bone cell absorption and osteolysis, or even bone destruction (4,5). Patients with bone metastases endure severe pain resulting in low quality of life and poor mental health, as well as loss of confidence in life (6). Morphine is a routine analgesic in the late stage of clinical treatment but with poor effect for patients with bone metastasis because of short onset time and side effects (7). Therefore, the effective analgesic treatment for patients with bone metastases is currently a hot topic in clinical research (8). Chemoradiotherapy, radionuclide, analgesic and bisphosphonate therapies are currently important methods for bone metastases from malignant tumors (9–11). In the treatment and prevention of complications of bone metastasis from malignant tumors, some studies have indicated that bisphosphonates are effective in alleviating pathological bone pain of patients (12). Bisphosphonates play an important role in reversing bone destruction such as bone cell absorption and osteolysis, especially pamidronate disodium, one of the bisphosphonates, which was effective in inhibiting bone resorption and osteolytic bone metastasis (13). Zoledronic acid and pamidronate disodium are widely-used bisphosphonates clinically (14,15). Therefore, this study aimed to analyze the curative effect and side effects of pamidronate disodium in the treatment of elderly patients with advanced metastatic bone cancer. Patients and methods Patients data A total of 160 elderly patients with advanced metastatic bone cancer admitted to Affiliated Hospital of Nantong University (Nantong, China) from February 2012 to January 2015 were divided into in the chemotherapy group (n=60) that received routine therapy and the pamidronate disodium group (n=100) that received pamidronate disodium therapy based on the chemotherapy. Patients in the chemotherapy group ranged in age from 46 to 72 years, with an average age of 53.15±4.93 years. Patients in the pamidronate disodium group ranged in age from 47 to 69 years, with an average age of 53.67±4.81 years. Inclusion criteria were as follows: i) patients who met the international diagnostic criteria for malignant tumors and were diagnosed as bone metastases through pathological examination and medical imaging technology (16); and ii) patients who did not have surgical treatment. Exclusion criteria were as follows: i) presence of neurological diseases, liver and renal dysfunction and organic diseases, severe complications, failure of chemotherapy and follow-up. The study was approved by the Ethics Committee of Affiliated Hospital of Nantong University. Signed informed consents were obtained from the patients or guardians. Methods Treatment methods: Both groups received chemotherapy according to the clinical medication guidelines for primary tumors. Based on the chemotherapy group, patients in the pamidronate disodium group were treated with 45 mg pamidronate disodium (SFDA approval no. H19980200; Shenzhen Neptunus Pharmaceutical Co., Ltd.) and 500 ml sodium chloride solution with 0.9% concentration twice a week, once a day, four weeks a course and three courses for the treatment. Liver and kidney functions were measured each week. Evaluation of curative effect Criteria of pain relief effect and bone lesions were as follows: according to Verbal Rating Scale (VRS) (17), pain is divided into grade 0 to III: the higher the grade, the more severe the pain. The pain grading standard is as follows: downregulation by one level indicating effectiveness, by two levels indicating marked effectiveness, upregulation or unchanged indicating ineffectiveness. The total effective rate of pain relief = (marked effectiveness)/effectiveness + effectiveness/total number of cases ×100%. Evaluation of curative effect of bone lesions: CR indicates the disappearance of bone lesions for 4 weeks or less. PR indicates that the area of diseased tissue reduced and the density of calcification of bone lesions was 4 weeks or less. NC indicates no change in the area of bone lesions. PD indicates that new bone lesions or the area of original bone lesions increased. The total effective rate of bone lesions = (CR+PR)/total number of cases ×100%. Statistical analysis SPSS19.0 (Bizinsight Information Technology Co., Ltd.) software was used for statistical analysis. The enumeration data were expressed as the number of cases/percentage [n (%)] and tested by χ2 test. The measurement data were expressed as mean ± standard deviation and tested by independent sample t-test at the same time-point. P<0.05 was considered to indicate a statistically significant difference. Results General data of patients There was no significant difference in general data between the two groups (P>0.05; Table I). Table I. General data of the two groups [n (%)]. Table I. General data of the two groups [n (%)]. Variables Pamidronate disodium group (n=100) Chemotherapy group (n=60) t/χ2 P-value Age (years) 53.67±4.81 53.15±4.93 0.656 0.513 Sex 0.220 0.639 Men 63 (63.00) 40 (66.67) Women 37 (37.00) 20 (33.33) BMI (kg/m2) 18.93±4.12 18.42±3.84 0.778 0.438 Types of cancer Esophageal carcinoma 15 (15.00) 7 (11.67) 0.351 0.553 Lung cancer 24 (24.00) 16 (26.67) 0.142 0.706 Cervical cancer 20 (20.00) 12 (20.00) 0.000 1.000 Prostate cancer 13 (13.00) 5 (8.33) 0.818 0.366 Nasopharyngeal cancer 28 (28.00) 20 (33.33) 0.508 0.476 Number of bone metastases 0.886 0.347 1 68 (68.00) 45 (75.00) >1 32 (32.00) 15 (25.00) [i] BMI, body mass index. Comparison of pain relief between the two groups after treatment The pain relief effect in the pamidronate disodium group was as follows: patients with marked effectiveness: 39 cases, effectiveness: 46 cases, ineffectiveness: 15 cases. While in the chemotherapy group, patients with marked effectiveness: 21 cases, effectiveness: 12 cases, ineffectiveness: 27 cases. The total effective rate of pain relief in the pamidronate disodium group was 85%, higher than that in the chemotherapy group (P<0.001; Table II). Table II. Comparison of pain relief between the two groups after treatment [n (%)]. Table II. Comparison of pain relief between the two groups after treatment [n (%)]. Groups n No. of marked effectiveness No. of effectiveness No. of ineffectiveness or deterioration Total effective rate Pamidronate disodium 100 39 (39.00) 46 (46.00) 15 (15.00) 85 (85.00) Chemotherapy 60 21 (35.00) 12 (20.00) 27 (45.00) 33 (55.00) χ2 – – – 17.430 P-value – – – <0.001 Comparison of curative effect of bone metastases between the two groups after treatment The curative effect of bone metastases in the pamidronate disodium group was: CR cases: 35, PR cases: 19, SD cases: 24, PD cases: 22; while in the chemotherapy group was: CR cases: 11, PR cases: 1, SD cases: 28, PD cases: 20. The total effective rate of pain relief in the pamidronate disodium group was 54%, higher than that in the chemotherapy group (P<0.001; Table III). Table III. Comparison of the curative effect of bone metastases between the two groups after treatment [n (%)]. Table III. Comparison of the curative effect of bone metastases between the two groups after treatment [n (%)]. Groups n CR PR SD PD Total effective rate Pamidronate disodium 100 35 (35.00) 19 (19.00) 24 (24.00) 22 (22.00) 54 (54.00) Chemotherapy 60 11 (18.33) 1 (1.67) 28 (46.67) 20 (33.33) 12 (20.00) χ2 – – – – 18.360 P-value – – – – <0.001 Analysis of analgesic time and duration between the two groups The analgesic onset time in the pamidronate disodium group was 4.59±0.74 h, while the chemotherapy group was 8.12±0.62 h. Compared between the two groups, the onset time in the pamidronate disodium group was earlier than that in the chemotherapy group (P<0.001). The duration of analgesic time in the pamidronate disodium group was 21.01±2.45 h, while the chemotherapy group was 12.45±3.15 h. The duration of analgesic time in the pamidronate disodium group was longer than that in the chemotherapy group (P<0.001; Table IV and Fig. 1).
Open Access
Published: 24 May 2021
Frontiers in Virology, Volume 1;

In the last decades, emerging and reemerging infectious diseases marked the third epidemiological transition (Figure 1A), characterized by: (i) identification of new emerging diseases; (ii) increased incidence and prevalence of preexisting infectious diseases; (iii) appearance of antimicrobial-resistant strains (1). These trends occur within a context of globalization, international trade, migration, and ecological changes. Figure 1. The perpetual challenge of viral infections. (A) Epidemiological transitions. Communicable diseases became known when human beings organized in prehistoric hunter-gatherer societies. About 10,000 years ago, the Neolithic Revolution, also called the first agricultural revolution occurred, which was characterized by a transition from a nomadic hunting and gathering lifestyle to sedentariness (1). The introduction of agriculture and of domestication and herding of animals created the conditions for a rise in infectious diseases, known as the first epidemiological transition. Infectious diseases such as malaria, tuberculosis, leprosy, influenza, and smallpox were already present several millennia ago. In the mid-nineteenth century, the second epidemiologic transition took place with the industrial revolution, featured by a shift from infectious to chronic and degenerative diseases. In the last decades, emerging and reemerging infectious diseases marked the beginning of the third epidemiological transition, characterized by three main trends: (i) identification of a substantial number of new diseases associated with significant morbidity and mortality in human beings; (ii) an increase in incidence and prevalence of preexisting infectious diseases thought to be under control; (iii) appearance of antimicrobial-resistant strains that are difficult to manage (1). These trends occur within a context of globalization, international trade, migration, and ecological changes that affect the climate and the environmental equilibrium. (B) Major viral pandemics in human history. Smallpox, one of the greatest scourges in human history, first appeared in agricultural communities in northeastern Africa about 10,000 B.C.E, spreading throughout the Old World (2). Smallpox was endemic to Europe, Asia, and Africa for centuries, killing millions of people. Variola virus, caused devastation on native populations because the indigenous populations lacked natural immunity to smallpox, wiping out 90 to 95% of the indigenous people over a century. It is unknown how many people smallpox has killed throughout centuries, but only in the twentieth century, smallpox estimated mortality is of 300 to 500 million people. Smallpox could be eradicated thanks to massive vaccination campaigns (3, 4). The 1918 pandemic influenza (Spanish flu), caused by an antigenically distinct H1N1 influenza virus, occurred in three different waves, starting in March 1918, and waning by the summer of 1919 (5). The virus infected about one-third of the planet's population (~500 million people at that time) and made an estimated 50 million victims. During the 1918 influenza pandemic, the cause of the Spanish flu was unknown; there were no antivirals to treat the disease or vaccines to prevent infection, no antibiotics for therapy of secondary bacterial infections, and no healthcare notion. The main response to the Spanish flu was based on physical and social distancing, isolation, and quarantine. The Spanish Flu marked an inflection point in global health as the concept of socialized medicine emerged and the importance of coordinating public health at the international level was recognized. Since the discovery of HIV/AIDS [beginning of 1980's, more than 77 million people have been infected with this virus, and about 35 million people have died of AIDS (6, 7). To date, around 37 million worldwide live with HIV, of whom 22 million are on treatment. Although there is no cure for AIDS and no vaccines to prevent HIV, HAART can successfully control HIV. The HIV/AIDS pandemic have had a negative influence on the global economy, though Africa, where the highest percentage of HIV/AIDS cases occur, was particularly affected. Developed countries engaged with the developing world to give access to antiretroviral therapy and to establish a health care infrastructure. In December 2019, a cluster of pneumonia cases of unknown etiology was reported in Wuhan City (Hubei province, China) (8, 9). By mid-January 2020, a novel coronavirus, named SARS-CoV-2, was identified as the etiologic agent of this outbreak. The COVID-19 pandemic is not only a health crisis; it affects our society and the economy. The impact of the pandemic will differ from country to country, but at a global scale, it will increase poverty and inequalities, propelling the amount of people living in conditions of extreme poverty in the next decade. COVID-19 is changing the trajectory of development the world had before the emergence of SARS-CoV-2. (C) Examples of newly emerging and reemerging viral diseases in the past decades. The (re)emergence of infectious diseases is mostly the consequence of the changes humans introduced in nature. Most zoonosis have occurred because of an increase contact between human beings with animals, linked to the agricultural revolution of the last decades (10). Bush meat handling and consumption of non-human primates is an effective route for the transmission of zoonotic pathogens into human populations. Several viruses, such as HIV/AIDS (via SIV) and HTLV, associated with leukemia, lymphoma, and myelopathy, have been related to pathogens of non-human primates. Bush meat is also linked to the reemergence of Ebola virus in 2015–2016. Since the 1918–1919 Spanish flu, other less severe influenza pandemics have occurred in 1957 (H2N2 Asian Flu), 1968 (N3H2 Hong Kong Flu), and 2009–2010 (H1N1 Swine Flu) (11). Besides, several epidemics caused by novel avian influenza viruses, including the Asian H7N9 virus, and the Asian H5N1 virus, which normally do not infect humans, have occurred after exposure to infected poultry or contaminated environments. Vector-borne diseases are highly sensitive to climate changes (10). Arthropod-borne viruses, including dengue virus, chikungunya virus Zika virus, West Nile virus, and Crimean Congo hemorrhagic fever virus have reemerged in many tropical and subtropical areas in the two last decades. In addition to SARS-CoV-2, two other coronaviruses crossed animal-human barriers and emerged as major human pathogens in the twenty-first century, causing deadly diseases in humans (12). SARS-CoV was reported by China in 2002 and MERS-CoV by Saudi Arabia in 2012. Unfortunately, no actions were taken to reduce the risks of emergence of new coronaviruses following these two alerts. The outbreaks of novel human coronaviruses are the result of the interactions between humans and animals. Preparedness to face the appearance of other pandemics caused by another coronavirus, an influenza virus, a paramyxovirus, a flavivirus, or any other known or a new zoonotic virus is mandatory. Lessons can be learned from previous coronavirus outbreaks and from the deadly Spanish Flu pandemic, taking into account the (dis)similar biological features and clinical characteristics of the illnesses these viruses caused (13, 14). The COVID-19 pandemic was unpredictable and overwhelming, completely, and radically changing our lives and lifestyle, causing traumatic events comparable to a war world for some people. It has resulted in millions of people infected around the World and thousands of deaths. What is more stressful is that there is still a great uncertainty on how this crisis will evolve and on the possible post-crisis scenarios. The efficacy and public uptake of the already available vaccines and of those arriving to the market soon as well as the development of a specific antiviral treatment will be key factors for the recovery of this unprecedented global health crisis. Highly pathogenic viruses have been related to some of the major pandemic and epidemics that affected the course of human history [(15); Figure 1B]. Since HIV outbreak in the 80s, we have witnessed the discovery of other highly pathogenic viruses as well as reemerging pathogens (Figure 1C), including SARS-CoV-2 responsible for the currently ongoing COVID-19 pandemic. Vaccines have clearly been game-changers in the fight against viral diseases. Antivirals play an invaluable role mainly to control the HIV pandemics, the hepatitis C, and several herpesviruses where vaccination has so far failed. Successful control and eradication of pandemic viruses can only be achieved by prophylactic vaccination while antivirals can decrease the morbidity and mortality related to the viral infection. However, using effective antivirals to fight pandemics or any viral disease which appears as epidemics could be pivotal to control the spread of (re)emerging viruses. The armaments (hygiene, vaccines, and antivirals) we dispose to fight against viral diseases are continuously developing to counteract not only (re)emerging viral pathogens but also endemic viral pathogens (e.g., HBV and herpesviruses) that had been infecting and co-evolved with human beings over very long time periods. Though several approaches have been used to control viral disease (improved sanitation, quarantine, and vector control), successful disease prevention has occurred mostly thanks to vaccination (16). Traditional vaccination strategies, based on inactivated viral preparations or live-attenuated strains, have successfully controlled dreadful viral diseases (e.g., smallpox, polio, and measles). Smallpox eradication, thanks to massive vaccination worldwide, is one of the greatest achievements of humankind. Without vaccination, it is projected that smallpox would cause as many as 5 million deaths per year, measles 2.7 million deaths and polio 600,000 deaths or paralytic cases (17). In addition to traditional inactivated or live attenuated vaccines, virus-vectored, subunit, viral-like particle, nucleic acid-based vaccines, and rational vaccine design provide innovative technologies to surmount existing challenges of vaccine development. These novel vaccine strategies significantly provided insights into vaccine immunology, and proved extremely useful in rapid vaccine development for emerging infectious diseases. Safer formulations based on purified recombinant proteins led to effective vaccines against HBV, rotavirus, and HPV. Vaccines based on nucleic acids have gained popularity as RNA and DNA vaccines can be made fast because no culture or fermentation is required, instead synthetic processes are used. Due to the simplicity of in vitro mRNA transcription, RNA vaccines can be developed and changed extremely fast and, importantly, they are safe in theory and have shown acceptable tolerability. Though they are not cost-effective, are expensive, not very easy to produce in high quantity, and hard to deliver, the enormous global collaborative research efforts and immense investments made it possible that the RNA vaccines reached commercialization in an unprecedented time and are in the frontline combating the COVID-19 pandemic. However, for many important known viral pathogens (HIV, herpesviruses others than VZV, HCV, and RSV), effective vaccines are not available. Fully protective vaccination against influenza virus continues to be a challenge. Newer vaccine technologies are also urgently needed to combat (re)emerging viruses. Several substantial issues must be considered for viral vaccine development, at the level of basic virology and efficacy (18). A main barrier in vaccine development is pathogen variability due to: (i) huge genetic diversity among viral types (e.g., >160 different rhinovirus serotypes); (ii) antigenic shift and drift (e.g., influenza virus requiring yearly vaccine formulations); (iii) viruses with high mutation rate (e.g., HIV and HCV); (iv) zoonotic viruses (e.g., SARS-CoV, MERS, SARS-CoV-2, influenza H5N1 and H7N9). Zoonotic viruses may show limited variability in their natural hosts; however, these viruses have the potential to infect humans (an immunological naïve population). If the pathogens establish themselves in the new host, in the process of adaptation to humans, new variants will appear, increasing the viral genetic variability. Although SARS-CoV-2 shows less genetic variability than HIV or HCV, variants with higher transmissibility are being detected, raising concerns on vaccine efficacy. A major hurdle in HIV vaccine development is linked to HIV extensive genetic variability (19). For dengue vaccines, imbalanced immunity against the four serotypes is a major drawback (20). Molecular mimicry between pathogenic viruses and human proteins may lead to immune cross-reactivity playing a role in the etiologies of different inflammatory and autoimmune diseases as the reaction of the immune system toward the pathogenic antigens may also injure the similar human proteins. In some SARS-CoV-2 infected patients, molecular mimicry–induced adverse autoimmune-related manifestations (e.g., transverse myelitis) have been reported, highlighting the need for continuous surveillance of vaccine side-effects (21). Antibody-dependent disease enhancement (ADE) occurs when antibodies generated during an immune response can recognize and bind to a pathogen, but they cannot prevent infection; instead, these antibodies allow the virus getting into cells or triggering harmful immunopathology. This complication has been an impediment in development of vaccines for dengue, RSV, and coronavirus disease in cats, and is a potential barrier to COVID-19 vaccines (22). Anti-SARS-CoV-2 antibodies could exacerbate COVID-19 through ADE, which is a general concern for vaccine development because the mechanisms that trigger antibody protection against any virus have theoretically the potential to intensify the infection or exacerbate immune responses. Understanding host genetic variability is another important challenge in vaccinology as host gene polymorphisms influence vaccine-specific immune responses, a phenomenon demonstrated for HBV, measles, rubella, mumps, smallpox, cytomegalovirus, and influenza virus (18). Ethnicity, race, age, and sex can impact vaccine-induced immune responses, leading to variability of immune responses. The lower immune response to vaccination in the elderly, young children, and patients with congenital or acquired immunodeficiency needs special consideration. Immunodominance is a crucial principle in host response to viral infections since the immune system recognizes and respond only to a small set of immunodominant epitopes despite the generation of hundreds of distinct antigenic peptides. Pathogens exploits host immunodominance by modifying immunodominant epitopes allowing the virus the evasion of host immune responses (23, 24). Due to the high complexity of the human immune system, we have an incomplete understanding of immunity development at the system-level. For some pathogens, e.g., CMV, we still do not fully comprehend how protective immunity is conferred and therefore, we are unable to reliable predict the outcome of a natural infection or of vaccination. Neutralizing antibodies serve as a correlate of immunity for many viruses (e.g., rubella) but for some pathogens, antibody presence is clearly not a correlate of immunity/protection since infected individuals are not protected against disease despite development of antibodies. Lack of correlates of immunity/protection for some pathogens, e.g., HIV, CMV, is an important barrier in vaccine development. Another big challenge is vaccination acceptance because of fear of some individuals that vaccines may cause diseases (e.g., autism or multiple sclerosis), despite lack of scientific evidence. A growing vaccine hesitancy movement in USA and Europe in the last years has led to decreased vaccination rates causing an increase in global measles cases (>400,000 in 2019), reversing the progress done over the last decades in measles eradication (25). Viral genomics is of great utility for determination of viral strains diversity, virulence factors identification, selection of conserved regions, construction of vectors, generation of recombinant proteins, attenuation of vaccine strains, and design of nucleic-acid based vaccines. Identification of genetically conserved regions allows targeting epitopes present across multiple strains and thus cross-protective immune responses, highly valuable to develop universal influenza vaccines, and pan coronavirus vaccines to be prepared for a next pandemic. Systems biology and vaccinomics are used to understand the complex interactions of the different immune components in response to a natural infection or following vaccination. Transcriptomics, epigenomics, proteomics, and metabolomics have proven extremely valuable in understanding immune function, host-pathogen interactions, and pathogen genetics, providing insights into how vaccination can lead to antibody-dependent enhancement, a complication seen in development of vaccines for dengue, RSV and coronavirus disease in cats, and thus a potential barrier to COVID-19 vaccines (22). A viral genetic approach together with host genetics analysis are needed to reveal the factors determining host immunodominant responses against dominant epitopes and how viruses exploits this phenomenon to evade the host immune system. Structural vaccinology made possible mapping viral epitopes onto the three-dimensional structure of viral proteins, determination of antibody-antigen complexes (important to understand critical antibody functionality, such as neutralization) and identification of critical conserved regions (that can be targeted for more efficient immune responses). Human genome-wide association studies are being used to delineate inter-individual variability, non-responders populations and impact of sex, age, race, and ethnicity in vaccine-induced immunity (26). A fundamental focus of vaccine development for immunosuppressed persons is the activation of innate immune response without using life-attenuated vaccines. To increase the immunogenicity of subunit vaccines, the use of adjuvants is necessary. Since the first generation of adjuvants (aluminum salts and mineral oil-in-water emulsions), much efforts have been done toward delivery of novel safe adjuvants (27). Although several conventional viral vaccines (attenuated or inactivated pathogens or protein subunits) have been produced, new vaccines are being developed, consisting of nucleic acid that encode the desired antigen(s). These novel vaccines are designed based on data obtained from systems biology, adjuvant discovery, new formulations and vaccine vectors, immunization routes, host factors studies, and results from animal models. CRISPR/Cas9 genome editing technology was used to excise virulence genes and create viral vaccines (18). Monitoring of vaccine safety is a necessity and genetic approaches (immunogenomics, system biology, computational modeling and bioinformatics, termed “adversomics”) are being used to better understand genetic and non-genetic determinants of aberrant vaccines responses at molecular level (18). Significant efforts need to be conducted at the scientific level and public advocacy level to restore confidence in vaccines. The COVID-19 pandemic has increased fear and uncertainty because of rapid SARS-CoV-2 vaccine development. The foundations of antiviral therapy began in the early 1950s with the search of new molecules capable of hindering DNA synthesis for anticancer treatments. In the 1960s, scientists had doubts that specific drugs could be found to fight viruses. Acyclovir approval (in 1982) was a breakthrough, providing proof-of-concept that highly effective and non-toxic antivirals could be developed, pioneering a more rational approach to antiviral drug development (28). At present, 106 drugs have been licensed for therapy of viral diseases. Despite the vast diversity of human viruses (over 200 currently known), antivirals are approved only for a handful of viruses (HIV, HCV, influenza virus, RSV, HBV, HPV, herpesviruses, and SARS-CoV-2 (29). Half of the approved antiviral drugs are used for HIV therapy. The development of effective HIV treatments was remarkable in speed and success, boosting antiviral research. After the approval of the first antiretroviral drug in 1987, a breakthrough in HIV therapy was the introduction in mid-1990's of HAART able to reduce AIDS-related deaths by 60–80% (30). Although tremendous efforts have been done in antiretroviral therapy, culminating in the one-pill once-a-day regimens, there are still about one million people dying of AIDS per year. The antiviral drugs available to treat viral infections have saved tens of millions of human lives over the last decades, and they will continue to be a cornerstone for treatment of current as well as (re)emerging viral infections. Although great achievements have been made, there are big challenges to undertake. Antiviral compounds displaying broad-spectrum activity against different virus subtypes or genotypes should be developed. Several anti-HCV drugs show activity against genotype 1 but not against other genotypes. However, acyclovir, foscarnet, ribavirin, tenofovir, and cidofovir are used for therapy of infections caused by different viruses, indicating that development of broad-spectrum antivirals is doable, which is of extreme importance as first-line measure for (re)emergent new viruses. We also still need antiviral drugs that are more potent than the currently available antivirals to suppress completely viral replication, limiting drug-resistance, a major cause of HIV therapy failure. At present, we are unable to eradicate herpesviruses and HIV from their latent state, hence we need to tackle the viral genomes that persist in the host. Effective treatments to treat co-infections with different viruses (HBV/HIV, HCV/HIV) need to be developed. Importantly, we need cost-effective and non-toxic antivirals. Although viruses are intracellular parasites that rely on the host cells for replication sharing many stages of their replicative cycle with cellular life cycles, most antivirals target specific steps of virus multiplication. It is challenging to identify compounds that specifically shut down viral replication without harming the host cells. In addition, some viruses may rapidly acquire resistance to a drug (31, 32). High-throughput screening is based on evaluation of hundreds of thousands of natural and synthetic chemicals for antiviral activity and toxicity with the aim at identifying candidate compounds (33). Thanks to the advances in molecular virology enabling production of functional viral proteins for biochemical testing, antivirals for viruses that cannot be grown in cell culture can be discovered. Another alternative for the discovery of new antivirals is rational drug design where modifications are made to a chemical structure with the aim of increasing its antiviral potency and/or reducing its cytotoxicity. Modeling programs are used to computationally screen chemicals for predicting interactions with viruses, reducing lab work. There are currently being reported in silico docking studies or other computer-based predictions of antiviral activity without support of biological assays (34). Although this is an interesting approach for accelerating and reducing drug discovery and development process costs, theoretical findings should be sustained by biological data to provide promising new insights and speed up the drug discovery workflow. Computational drug discovery methods (e.g., molecular docking, molecular similarity calculation, pharmacophore modeling and mapping, sequence-based virtual screening, and de novo design) can be applied at different stages in drug discovery and development, being particularly important for target identification in conjunction with biological validation. Preclinical evaluation in an animal model before clinical trials is a critical step (33). Unfortunately, many initially promising drugs fail to show efficacy in vivo, or prove toxic to animals, and an important number of candidates fail in clinical trials. The use of in vitro systems that are not representative of the in vivo situation can explain, at least in part, this failure. Many antiviral tests use a cell type that is different from the one the virus infects in the host. Numerous assays utilize established cell lines, which are immortalized cells or even worse transformed cells with alterations in several cellular pathways. Drug metabolism and viral replication can be different in these cells than in normal primary cells. Cell culture adapted viral strains that have acquire genetic changes or loose part of their genome are often used. Most in vitro systems are based on cells grown in monolayers that do not always behave as in the natural host. Human-specific viruses, for which no animal model exist, pose a major problem for drug-preclinical testing and data obtained in animals cannot directly be extrapolated to the human situation. Therefore, we need to develop and validate novel in vitro tests that can mimic the in vivo situation, such as three-dimensional cultures, and to develop animal models for which data can be extrapolated more faithfully to the human situation. The process required to develop a new antiviral drug is complex, highly expensive (an estimated 2.8 billons for a single drug) and long (on average 12 years). In emergency situations (COVID-19 pandemic), the search for an effective treatment can be accelerated through drug repurposing (35); a strategy that takes a drug already licensed for therapy of another disease and repurpose it to be used to treat an infection caused by a novel virus. Because safety and pharmacokinetic profile of the potential drug-candidates are already known, a limited number of in vitro studies to evaluate their antiviral activity and specificity is mandatory. Most approved antiviral drugs are small molecules that inhibit the replication of the viral genomes. During the last years, efforts are being made to target different steps of the viral replicative cycle (29). Besides, new treatment perspectives including nanoparticles, monoclonal antibodies, and the CRISPR/Cas-9 system are being explored (36). Nanoparticles are used in different formats and composition as delivery system of antiviral molecules to improve their therapeutic efficacy and reduce their toxicity (37). Both polyclonal and monoclonal neutralizing antibodies can be potentially used as antivirals because of their capacity to target specific epitopes. Despite some limitations of neutralizing antiviral antibodies as therapeutic agents, they have potential for prevention and treatment of several viral infections (Ebola, HIV, chikungunya virus, MERS-CoV, SARS-CoV, and SARS-CoV-2) (38). The CRISPR/Cas-9 technology is being used in different antiviral strategies, including: (i) modification of viral entry receptors, (ii) knock-down of host viral factors, (iii) induction of host restrictions factors, (iv) excision and removal of viral genomes that are integrated in the host genome or persisting as episomes (39, 40). To date, only a few approved antivirals target the host systems (28). Even though much efforts have been directed toward the development of host cell-directed therapeutics with the advantage that they can potentially have a broad spectrum antiviral activity and a high genetic barrier to resistance, results have been disappointing, mostly due to toxicity issues. However, targeting host factors remains an active research area. Proteomics and genome-wide CRISPR screens can be used to reveal host factors critical for viral Infection (41, 42). We have experienced the global progress in infectious diseases control in the last years thanks to improved sanitation, effective vaccination and use of effective antiviral therapy. However, infectious diseases remain a leading cause of mortality worldwide, new viral diseases are emerging and known diseases are reemerging. Though new and improved vaccines and antivirals are being made, several endemic and (re)emerging viral diseases remain a threat for humankind. It is almost certain that we will face an increased number of viral diseases. Pathogenic viruses can move fast and unexpectedly spill over into new populations. The major epidemics and pandemics seen in the last decades and the social and environmental changes promoted by humans contributing to the emergence of these viruses forecast the appearance of a next pandemic. At present, politicians and key decision-makers pay full attention to COVID-19 but we need to learn from this cruel experience to rethink our approaches to future national and international preparedness (Figure 2). Figure 2. Pillars to improve pandemic preparedness and management. Of most importance, preparedness to manage the next pandemics needs to encompass the implementation of the discovery of novel vaccine and therapeutic strategies that can be rapidly made available, which will require important research efforts and investments, without neglecting research on known viral pathogens. Thanks to years of research on vaccine development for related coronaviruses, faster ways to manufacture vaccines, and colossal investments allowing the run of multiple trials in parallel, and regulatory agencies moving more rapidly than usual, COVID-19 vaccines could be delivered so quickly. This success might be beneficial for the development of vaccines against other pathogens though researchers were fortunate with SARS-CoV-2 as this virus does not mutate so fast and does not have sophisticated strategies for hindering the human immune system, unlike HIV, herpesviruses, or influenza. Herpesviruses have higher and multiple immune evasion capabilities (e.g., actively block antibodies from binding) and HIV and influenza have faster mutation rates. In contrast to vaccination, antiviral drugs for SARS-CoV-2 failed to deliver on their expectations. To date, clinically approved antivirals are available for only a limited series of viruses and it is imperative that this precarious situation changes and hopefully, the COVID-19 pandemic will boost antiviral research. SARS-CoV-2/COVID-19 pandemic has underscored the pivotal need for antivirals that can be rapidly employed before a (re)emerging virus reaches the global emergency status and more efforts should be put into the development of antivirals. The author confirms being the sole contributor of this work and has approved it for publication. The author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. AIDS, acquired immunodeficiency syndrome; CMV, cytomegalovirus; COVID-19, coronavirus disease 2019; CRISPR/Cas9, Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) and CRISPR-associated (Cas); HAART, highly active antiretroviral therapy; HBV, hepatitis B virus; HCV, hepatitis C virus; HIV, human immunodeficiency virus; HPV, human papillomavirus; HTLV, human T-lymphotropic virus; MERS, Middle East respiratory syndrome; MERS-CoV, Middle East respiratory syndrome coronavirus; RSV, respiratory syncytial virus; SARS, severe acute respiratory syndrome; SARS-CoV, severe acute respiratory syndrome coronavirus; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2; VZV, varicella-zoster virus. 1. Zuckerman MK, Harper KN, Barrett R, Armelagos GJ. The evolution of disease: anthropological perspectives on epidemiologic transitions. Glob Health Action. (2014) 7:23303. doi: 10.3402/gha.v7.23303 PubMed Abstract | CrossRef Full Text | Google Scholar 2. 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Emerging cellular targets for influenza antiviral agents. Trends Pharmacol Sci. (2012) 33:89–99. doi: 10.1016/ PubMed Abstract | CrossRef Full Text | Google Scholar Keywords: vaccines, antivirals, (re)emerging infectious disease, pandemics, epidemics, drug discovery, viral targets Citation: Andrei G (2021) Vaccines and Antivirals: Grand Challenges and Great Opportunities. Front. Virol. 1:666548. doi: 10.3389/fviro.2021.666548 Received: 10 February 2021; Accepted: 20 April 2021; Published: 24 May 2021. Edited by: Reviewed by: Copyright © 2021 Andrei. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. *Correspondence: Graciela Andrei, [email protected]
19 Ismics Annual Scientific Meeting
Innovations: Technology and Techniques in Cardiothoracic and Vascular Surgery, Volume 14, pp 63S-115S;

Systematic reviews of minimally invasive aortic valve surgery showed certain advantages over conventional surgery. New trends were introduced in aortic arch surgery. The aim of our study was to compare the results of conventional aortic arch replacement with minimally invasive technique (MIT). The sample comprised a total of 258 patients undergoing aortic arch surgery from 2009 to 2018 at our center. Minimally invasive surgical approach included J-ministernotomy and peripheral cannulation (right subclavian artery and femoral vein) and was performed in 21 (8.2%) patients; of them, 10 (47.6%) patients underwent frozen elephant trunk procedure, 2 (9.5%) elephant trunk procedure, and 9 (42.9%) hemiarch procedure ( Figure PC1-1 ). Propensity score matching produced 21 (ministernotomy vs. full sternotomy [FS]) well-matched pairs to correct for differences in baseline characteristics. Primary endpoints were in-hospital mortality, blood loss, complications, intensive care unit stay, hospital stay, and 30-day survival; secondary endpoints were 1-year follow-up survival, stroke, reinterventions, and reoperations. A p-value <0.05 was considered significant. Figure PC1-1. Of all 155 included patients, 42 remained after propensity score matching. After matching, there was no difference between groups in cross-clamp time (116 ± 41 [MIT] vs. 109±15 [FS], p = 0.467), circulatory arrest (53 ± 7 [MIT] vs. 48.5 ± 8 [FS], p = 0.059), antegrade bilateral cerebral perfusion (48 ± 13 [MIT] vs. 42.7 ± 9 [FS], p = 0.132). Blood loss (862 ± 96 ml vs. 1373.81 ± 96 ml, p = 0.001), postoperative drainage loss (388 ± 96 vs. 590 ± 96 ml, p = 0.001), ventilation time (7.8 ± 1.9 vs. 12.7 ± 1.5 hours, p = 0.001), intensive care unit stay (1.2 ± 0.4 vs. 5.6 ± 0.6 days, p = 0.001), and hospital stay (8 ± 1.2 vs. 14 ± 1.7 days, p = 0.001) were lower after MIT. Rate of pulmonary complications was lower in the MIT group (2 [9.6%] vs. 6 [28%], p = 0.05). One patient died from septic shock at 43 days after operation in MIT group. In-hospital mortality was 4.8% in both groups. One-year follow-up does not have any difference in both 95% (MIT) vs. 95% (FS) groups. MIT is associated with a lower blood loss, postoperative drainage loss, ventilation time, pulmonary complications, and shorter length of stay compared with conventional surgery. Partial sternotomy was not associated with a significantly increased mortality and postoperative complications. However, retrospective design and limitations of less number of patients require prospective, randomized trials to further define the safety and efficacy of the minimally invasive approach. Thoracic endovascular aortic repair (TEVAR) for the treatment of aortic dissection has experienced rapid development and has been widely accepted in the past 20 years. However, there still does not exist a stent graft especially designed for aortic arch, which can reconstruct the supra-arch vessels. Castor branched aortic stent graft system has obtained the regulatory approval from China Food and Drug Administration. It is globally the first branched stent graft especially designed for the aortic arch, with the single branch extending into the left subclavian artery. The present research was to evaluate the early results of Castor in complicated Stanford B dissection. Figure PC2-1. Fifteen consecutive patients who underwent TEVAR with Castor branched aortic stent graft system were retrospectively reviewed from June 2017 to December 2018. Indications were acute B dissection (n = 12), complicated type B dissection with retrograde dissection involving the mid-arch (n = 1), and mid-arch aneurysms of the inner arch curvature (n = 2). Perioperative clinical data were recorded. Follow-up time was 2–12 months. The median patient age was 56 (range, 46–83) years, and 14 of the 15 patients were male. There was no death, stroke, spinal cord injury, or retrograde type A dissection. All the cases were deployed MicroPort Castor stent. Mean operation time was 112 (range, 108–143) minutes. Mean duration of hospital stay was 7 ± 3 days (range, 3–10 days). Only one branch of the Castor stent was put into the left common carotid because the arch aneurysm was just near the left subclavian artery, which had to be occluded to protect the type I endoleak. During follow-up, no postoperative complications occurred, all target vessels remained patent, and there was no stent-related type I or type III endoleak. Castor branched aortic stent graft system could be a good alternative for patients with type B dissection encroaching into the left subclavian artery or the original tear located within 20 mm distal to the left subclavian artery and 15 mm distal to the left carotid artery. It could effectively avoid type III endoleak and long-term migration. Ministernotomy is an attractive option for proximal aortic procedures because it may allow for faster recovery and less postoperative pain. This study investigates the feasibility and safety of ministernotomy (MS) in aortic root replacement. Between 2000 and 2018, 142 consecutive patients underwent aortic root replacement. Forty-four patients underwent MS with extension to the right 3rd or 4th intercostal space. Ninety-seven patients underwent full sternotomy (FS). Exclusion criteria were cases involving acute dissection, deep hypothermia, and circulatory arrest, arch and hemi-arch, root abscess, and concomitant procedures. FS group had significantly more Marfan patients (12.4% vs. 0%, p = 0.01) and a trend toward more chronic dissections (0% vs. 8.3%, p = 0.06). Medial degeneration (95.6% vs. 73.2%, p = 0.001) and hypercholesterolemia (55.6% vs. 30.9%, p = 0.006) were significantly more common in MS group. Hospital mortality was 0% in MS vs. 1% in FS (p = ns). Stroke rate was 2.2% vs. 0% in MS compared to FS (p = ns). The rate of reoperation for bleeding was 0% vs. 5.2%, renal insufficiency was 0% vs. 0%, atrial fibrillation 24.4% vs. 23.7%, and prolonged ventilatory support was 8.9% vs. 9.3% in MS vs. FS groups, respectively (p = ns). Median bypass and cross-clamp times were 153 and 141 minutes for MS group and 187 and 167 minutes for FS group, respectively (p < 0.05). No differences in transfusions of packed red blood cells (1.0 vs. 1.5), fresh frozen plasma (1.3 vs. 1.3), and platelets (1.1 vs. 1.2) were noted in either group. Transfusion of cryoprecipitate was more frequent in FS (1.5 vs. 1.2, p = 0.01). The median intubation time was shorter in MS (6 vs. 17.5 hours, p < 0.001). The mean length of stay in MS and FS groups was 8 and 9 days, respectively (p = 0.14). The survival at 1, 2, and 3 years was 100% vs. 99%, 100% vs. 99%, and 100% vs. 98% for MS and FS patients, respectively (p = 0.54). MS is feasible with similar intra- and postoperative outcomes and has comparable mid-term survival to FS. Further studies are needed to assess the quality-of-life metrics and long-term survival. Treatment of thoracoabdominal aortic dissections (TAAD) frequently requires open repair with increased procedural risk. Conventional endovascular prostheses have had limited repairing TAAD due to inadequate fenestration coverage and inability to maintain branch vessel flow. We evaluated the outcomes of patients with TAAD treated with multilayer flow-modulating (MFM) stents. A retrospective analysis of a prospectively maintained institutional database was undertaken for all patients with TAAD treated with MFM stents (n = 21) between April 2014 and July 2018. Outcome data were collected, including stroke, paraplegia, branch vessel patency, endoleaks, degree of aortic remodeling, and death. Patients were followed with annual computed tomography angiography (CTA) scans and regular telephone interviews. Morphologic computational fluid dynamics analysis of CTA scans was performed using Momics and Ansys software to assess aortic remodeling as defined as a reduction in total aortic length along with changes to the volume and diameters of the true and false lumens. Male:female ratio was 16:5. Mean age was 49 years (27–73). Indications for treatment included chronic type B aortic dissection (n = 15), prior type A dissection repair with false lumen expansion (n = 5), and distal malperfusion post-acute type A dissection repair (n = 1). Proximal landing zones were zone 0 (n = 17), zone 2 (n = 3), and zone 3 (n = 1). Seventy-two stents were used (mean 3.42 devices/patient) and 136 branch vessels were covered. Procedural success was 100% with no strokes, paraplegia, acute kidney injuries, endoleaks, or deaths. There was 1 reintervention for an access sheath-related iliac artery dissection. Follow-up was available for all patients (average 18 months; range 1–51 months). At 3 years, branch vessel patency was 100% and there were no aortic-related deaths ( Figure PC4-1 ). Two patients died from non-aortic-related causes subsequent to their 2-year follow-up imaging. Positive aortic remodeling (reduction in volume and diameter of the false lumen) was observed in all patients. Figure PC4-1. MFM stents appear to provide a safe treatment option for TAAD patients, with low risk of complications. Patency is preserved to cover aortic arch and visceral side-branches and positive aortic remodeling is observed in the short term. Additional study is needed to better understand the role of MFM stents in the management of TAAD. The frozen elephant trunk (FET) procedure is a treatment of patients with extensive thoracic aortic disease. Despite modern cerebral perfusion strategies, due to the complex surgical technique, early mortality rates are high ranging from 6.4% to 15.8%. As patients with DeBakey type I dissections are primarily treated with nonstented grafts in many centers, subsequent redo operations due to residual dissections are frequently necessary. Therefore, we sought to identify prevalence and outcome of patients undergoing FET procedures as redo operation. One hundred consecutive patients who underwent FET surgery between October 2010 and November 2018 at our center were registered in a dedicated database and retrospectively analyzed. Clinical and follow-up characteristics were compared between patients undergoing FET as primary (primary group) or redo procedure (redo group). Twenty-four percent (n = 24) of the procedures were redo operations (redo group). Patients in the redo group were significantly younger when compared to patients receiving primary surgery (66.2 ± 11.6 years vs. 54.6 ± 12.1; p < 0.001). The EuroScore II did not significantly differ between groups (primary group: 14.0 ± 13.6; redo group: 10.0 ± 9.4; p = 0.32). Patients of the redo group suffered from genetic aortic syndrome (GAS) more frequently (5.7% [n = 4] vs. 54.2% [n = 13]; p < 0.0001). There was no significant difference in occurrence of postoperative acute kidney failure (primary group: 17.1% [n = 13]; redo group: 8.3% [n = 2]; p = 0.4), recurrence nerve palsy (primary group: 10.5% [n = 8]; redo group: 29.2% [n = 7]; p = 0.06), paraparesis (primary group: 2.6% [n = 2]; redo group: 0.0% [n = 0]; p = 1.00), transient neurological deficit (primary group: 2.6% [n = 2]; redo group: 0.0% [n = 0]; p = 1.00), and postoperative stroke (primary group: 11.8% [n = 9]; redo group: 4.1% [n = 1]; p = 0.44). Although not statistically significant, the 30-day mortality rate was 3 times lower in the redo group (14.4% [n = 11] vs. 4.1% [n = 1]; p = 0.28). The one case of death after redo surgery occurred on postoperative day 18 due to acute pancreatitis after an uneventful postoperative period, which was unrelated to the surgical technique. Treatment of residual aortic arch dissections with FET procedures performed as redo operation appears feasible and safe with low mortality and stroke rates. Redo FET procedures are mainly performed in relatively young patients frequently suffering from GAS. Reoperation for aneurysmal dilation of the aortic arch after ascending hemiarch repair for type A dissection occurs in approximately 5% of patients. This typically requires redo open heart surgery with circulatory arrest and is associated with significant morbidity rendering many patients unsuitable for redo open repair owing to their comorbid conditions. Endovascular arch repair is an attractive alternative for patients that develop aneurysmal degeneration of the aortic arch after ascending hemiarch replacement for type A dissection. We describe the first case of total endovascular aortic arch repair with prefabricated custom branch device reported in the United States. The case involves an 80-year-old gentleman with enlarging aneurysmal degeneration of his aortic arch and proximal descending thoracic aorta after ascending hemiarch repair with free-style aortic root replacement for type A dissection 3 years earlier complicated by perioperative hemorrhage and delayed sternal closure. His medical history was significant for hypertension, heart failure, metastatic prostate cancer, and aortic stenosis. Given his advanced age and comorbidities, the risk of open reoperation was prohibitively high. After discussions between vascular surgeons, cardiothoracic surgeons, and cardiothoracic anesthetists, and appropriate preoperative evaluation and imaging, the patient underwent total endovascular repair of the aortic arch and proximal descending thoracic aorta using a three-vessel branched arch device. He was extubated in the operating room and was in the intensive care unit for 1 night. He was transferred to the stepdown unit on postoperative day 1. He was discharged on postoperative day 2 with dual antiplatelet therapy. Branch devices are well described for treatment of thoracoabdominal aortic disease, but this is the first report of a custom-manufactured branch device used for total endovascular repair of the aortic arch in the United States. Total endovascular repair of the aortic arch has wide-reaching implications for the treatment of aortic disease. Further research is needed to determine long-term benefits in patients who are too frail to undergo open surgery, and the utility in lower-risk patients as well. Additionally, further research is needed to evaluate the results of endovascular repair for aortic pathologies involving the arch and ascending aorta. There is no standard timing of delayed repair for blunt thoracic aortic injury (BTAI). Complying with the BTAI grade proposed by Society for Vascular Surgery, we perform elective thoracic endovascular aortic repair (TEVAR) even for grade III (pseudoaneurysm) without secondary sign of injury (SSI), following the treatment of other trauma injuries. Stent-graft was placed more proximal beyond the left subclavian artery (LSA) as zone 2 landing TEVAR for BTAI to use the noninjured aorta as a proximal neck. LSA was aggressively preserved by physician-modified fenestrated TEVAR (F-TEVAR), if anatomically possible. Otherwise, LSA was simply covered. We report early and mid-term results of this strategy. From 2008 through 2017, 12 patients (53 ± 21 years, 8 male) underwent zone 2 TEVAR for BTAI within a median of 8.4 days (0–36) of injury. The injuries were caused by 10 traffic accidents (9 cars, 2 motorcycles) and 2 fall accidents. The mean Injury Severity Score and Trauma and Injury Severity score were 20.8 ± 7.0 and 0.7 ± 0.2, respectively. All the aortic injuries were categorized into grade III with pseudoaneurysm. Emergency TEVAR was performed in 6 patients (50%) with SSI (5: extensive mediastinal hematoma, 1: pseudocoarctation) and elective TEVAR was in 6 patients (50%) without SSI. The injuries of other organs were 4 cases of intracranial injury (33%), 6 cases of lung injury (50%), 7 cases of multiple rib fracture (58%), 5 cases (42%) of intraperitoneal organ injury, 4 cases of pelvic fracture (33%), and 1 mediastinum injury (8%). Successful deployment was achieved in all patients. LSA was preserved in 7 patients (58%) by F-TEVAR, whereas it was intentionally covered in 5 patients (42%) on emergency TEVAR. The following factors had significant differences between emergency and elective TEVAR: preoperative fibrinogen degradation product value (59.8 vs.14.3; p = 0.04), operation time (90.1 vs. 122.0 minutes; p = 0.06), initial heparin injection dose (2,416 vs. 4,500 units; p = 0.04), bleeding (405 ± 591 vs. 107 ± 205 ml; p = 0.05). Although hospital mortality due to traumatic intraperitoneal bleeding was observed in 1 patient (8%), there were no TEVAR-related complications as stroke, spinal cord ischemia, and retrograde type A aortic dissection. In the follow-up periods of mean 25 months [0–83), there were a type II endoleak from intercostal artery, and 1 patient (8%) who had the symptoms of arm claudication required LSA revascularization by additional axillo-axillary bypass grafting postoperatively on 16 months; however, there was no case of aorta-related mortality. In the case of grade III without SSI, our strategy of delayed repair could be acceptable. Zone 2 TEVAR for BTAI might be promising since the preservation of LSA flow by F-TEVAR ensures the reliable surgical outcomes. For acute aortic dissection type A (AADA) with large patent false lumen, total arch replacement (TAR) may be desirable to prevent acute visceral malperfusion and downstream aortic event in the late phase. We simplify and minimize the risk of the procedure by utilizing total debranching method, which is often performed concomitant with thoracic endovascular aortic repair. This is a retrospective single-center study. From November 2017 to May 2018, consecutive 5 patients who underwent TAR with total debranching of the supra-aortic vessels and a novel frozen elephant trunk technique for AADA were reviewed. Immediately after median sternotomy, total debranching of the right carotid, left carotid, and left axillary artery was performed with quadrifurcated graft. TAR was performed under moderate hypothermia with true lumen perfusion through the debranching graft. A frozen elephant trunk was inserted into the aortic arch, following closure of the orifice of the supra-aortic vessels. The ascending aorta was replaced with one-branch graft. Finally, the quadrifurcated graft was anastomosed to the graft. The procedure was successfully performed in all patients. Preoperative arch vessel malperfusion was observed in 4 patients. One patient had preoperative neurological symptom. The mean clamp time of the right carotid, left carotid, and left axillary artery was 12.4 ± 2.3, 13.1 ± 4.1, and 20.7 ± 6.5 minutes, respectively. The mean change of regional cerebral oxygen saturation (rSO2) during clamp of right/left carotid artery was 9.7 ± 4.5 on the right side and 13.7 ± 5.1 on the left side. The rSO2 values before and after clamp were statistically similar. After total debranching, there were no significant rSO2 changes through the procedure. The mean operative, cardiopulmonary bypass, and selective cerebral perfusion time was 443.1 ± 123.8, 152.7 ± 57.0, and 34.9 ± 10.4 minutes. There was no postoperative neurological complication. There was no 30-day mortality. Total debranching of the supra-aortic vessels with a novel frozen elephant trunk technique would facilitate TAR for AADA with minimizing the risk of procedure and obtaining optimal brain protection. Figure PC8-1. Postoperative three-dimensional computed tomography imaging. Various devices have been developed for surgical ablation of atrial fibrillation (AF) in order to simplify and replace the surgical incisions of the Cox-maze procedure. One of the most common devices presently used is the bipolar radiofrequency (RF) clamps. However, the relative efficacy of bipolar irrigated RF compared to non-irrigated clamps has not been investigated. Between May 2003 and December 2017, 764 patients underwent a biatrial Cox-maze IV procedure (CMP-IV) for refractory AF. Irrigated bipolar RF clamps were used in 156 patients (group A) while non-irrigated bipolar RF clamps were used in the remaining 608 patients (group B). Patients in group A were propensity score matched to those in group B, using a logistic model with nearest neighbor 1:1 matching and a 0.1 caliper algorithm. Freedom from atrial tachyarrhythmias (ATAs) was determined by either electrocardiography, Holter, or pacemaker interrogation at 3, 6, and 12 months and yearly thereafter and was compared between the 2 groups. The majority of patients in both groups had prolonged monitoring. One hundred fifty-one patients were propensity matched in each group using 18 preoperative variables. There were no preoperative differences between the 2 groups including age (63.9 ± 12.2 vs. 62.5 ± 11.3 years, p = 0.318), body mass index (31.0 ± 7.5 vs. 31.2 ± 7.6, p = 0.819), left atrial size (5.1 ± 1.0 vs. 5.1 ± 1.1 cm, p = 0.820), type (65% vs. 62% with nonparoxysmal AF, p = 0.720), duration of AF (median [interquartile range]) (42 [12, 93] vs. 48 [11, 84] months, p = 0.643), and ejection fraction (54.3% ± 11.1% vs. 55.7% ± 11.2%, p = 0.294). In comparison to group B, more patients in group A underwent CMP-IV via sternotomy (91% vs. 66%, p < 0.001). There were no differences in operative mortality or postoperative complications between the 2 groups. Early and late freedom from ATAs on or off antiarrhythmic drugs were similar between the two groups ( Figure PC9-1 ). Figure PC9-1. Freedom from atrial tachyarrhythmias in patients who underwent Cox-maze IV procedure using irrigated bipolar radiofrequency clamp (group A) compared to non-irrigated bipolar radiofrequency clamp (group B). The bipolar irrigated and non-irrigated RF clamps had similar complication rates and efficacy at restoring sinus rhythm at mid-term follow-up after a CMP-IV. Concomitant surgical ablation is an established procedure for patients with atrial fibrillation (AF) undergoing cardiac surgery. Different energy sources are available to perform surgical ablation. At the moment, there is no clear evidence which energy source is superior. We, therefore, compared bipolar radiofrequency (RF) with cryoablation in concomitant AF surgery. Between 2003 and 2013, 556 patients underwent concomitant surgical AF ablation in our institution. One hundred sixteen patients were treated with cryoablation (Cryo-group) and 164 patients were ablated with bipolar RF (RF-group) and were included in this retrospective data analysis. Rhythm monitoring was done by either 24-hour-Holter ECG (Cryo-group: 90 patients; RF-group: 86 patients) or implantable loop recorder (Cryo-group: 26 patients; RF-group: 78 patients). Logistic regression analysis was used to identify predictors for rhythm outcome. Primary endpoint of the study was freedom from AF at 12 months follow-up. Mean age was similar in both groups (Cryo-group: 68.9 ± 7.9 vs. RF-group: 70.3 ± 8.6; p = 0.194) and both groups consisted of predominantly male patients (Cryo-group: 77.5% vs. RF-group: 71.3%; p = 0.270). Paroxysmal AF was present in 50.4% of the Cryo-group and 39.9% of the RF-group; p = 0.086. There were no major ablation-related complications and no intraoperative death. Survival at 12 months was 97.9% and 95.6% in both groups; p = 0.299. Freedom from AF did not differ significantly between cryoablation and RF at 3 (Cryo-group: 52.3% vs. RF-group: 61.9%; p = 0.124) and 6 months (Cryo-group: 66.7%; RF-group: 71.1%; p = 0.497). At 12 months, freedom of AF was significantly higher in the RF-group (78.7%) compared to the Cryo-group (63.4%); p = 0.006. During 12 months follow-up, cardioversion (RF-group: 9.5% vs. cryo-group: 5.3%; p = 0.215) and catheter-based ablation (RF-group: 3.6% vs. cryo-group: 2.6%; p = 0.648) were performed similarly often in both groups. Multivariate logistic regression analysis for freedom of AF at 12 months showed simultaneous double-valve procedures (odds ratio [OR] 0.045; p = 0.019) and longer duration of AF (OR 0.835; p = 0.042) as negative predictors in the Cryo-group and paroxysmal AF (OR 2.701; p = 0.037) as positive predictor in the RF-group. In our studied cohort, bipolar RF was more effective to restore sinus rhythm at 12 months compared to cryoablation. Predictors for freedom from AF are shorter duration of AF (cryoablation) and paroxysmal AF (RF). Catheter ablation is the cornerstone of treatment for paroxysmal atrial fibrillation (AF). Alternative techniques have been developed, such as minimally invasive epicardial ablation. The aim of this study is to report the efficacy and safety of thoracoscopic epicardial left atrial ablation (TELA) procedure in patients with paroxysmal AF. Between April 2011 and June 2017, 56 patients (77% males) with paroxysmal AF (mean CHA2DS2-VASc2 Score 2.0 ± 1.6) underwent TELA, including bilateral pulmonary vein isolation, ganglia mapping and ablation, left atrial dome lesions, superior vena cava lesion, and left atrial appendage exclusion. All patients received an internal loop recorder, 30 days postoperatively. Antiarrhythmic and anticoagulation therapies were discontinued at 90 and 180 days postoperatively, respectively, if patients were free of AF recurrence. Failure was defined as ≥2 minutes of continuous AF or flutter on any internal loop recorder download. Figure PC11-1. During the follow-up period (36.8 ± 21.1 months), 66% of patients (n = 37) were free of AF, atrial flutter, or tachycardia recurrence. Success rates were 88% (n = 49), 84% (n = 47), 77% (n = 43), 70% (n = 39), 68% (n = 38), and 66% (n = 37) at 6 months, and 1, 2, 3, 4, and 5 years, respectively. One patient experienced superior vena cava injury during the procedure and recovered without complications. Otherwise, no major procedural complications occurred in this group of patients, including major bleeding, and cardiovascular or cerebrovascular events. In this single-center experience, TELA was an efficacious procedure for patients with paroxysmal AF and seemed to be safe. The sympathetic nervous system has an important role in the production of ventricular tachyarrythmias. Sympathectomy with denervation of left lower fibers of stellate ganglion up to T4 level has shown long-lasting benefits and is an important consideration in treatment for these patients. We retrospectively analyzed 62 patients who underwent left video-assisted thoracoscopic (VATS) sympathectomy at our institution from September 2008 to October 2018. One approach involved a 3-port axillary access technique while the other approach employed a single port in the axilla. All patients underwent intubation to allow for left lung isolation. The sympathetic fibers from lower third of stellate ganglion to T4 level were cauterized. At the end of all procedures, air was evacuated and no intraoperative intercostal drains were inserted. Patient demographics, indication for sympathectomy, procedural technique, operating times, length of hospital stay, need for postoperative chest drain, electrocardiographic outcomes, and complications were noted. Of the 62 patients, 53 had long QT syndrome, 8 had catecholaminergic polymorphic ventricular tachycardia, and 1 patient had drug-induced long QT. The mean age was 22 years. The indications in most of them were syncopal episodes, which led to the diagnosis. Many patients had family members with long QT syndrome. The mean procedural time was 23 minutes. Two patients required chest drain postoperatively for pneumothorax. Patients were discharged home in a mean of 2.0 days. Shortening of QT interval was seen in approximately 62% of patients. The requirement for implantable defibrillators (ICD) later was roughly 28%. Compensatory hyperhidrosis was seen in 9% and partial Horner’s syndrome in 8%. Only 2 patients had mild left ptosis persisting for longer than 6 months. VATS sympathectomy is a simple uncomplicated promising adjunctive therapy in patients with symptoms and could reduce the load of sudden death due to life-threatening arrhythmias. This operation is to be considered in all patients who fail optimal medical management and who have frequent discharges of their defibrillator devices. Many patients could do away with ICD for a longer time with this procedure. Thromboembolic (TE) stroke remains a common and morbid complication of atrial fibrillation (AF) despite maximal medical therapy. Open surgical control of the left atrial appendage, in patients with AF, has been associated with a reduction in the incidence of stroke. Minimally invasive surgical approaches to the left atrial appendage provide an attractive option facilitating increased access for patients. We sought to investigate the incidence of TE stroke in our patients who underwent left atrial appendage exclusion and compare those outcomes to expected stroke rates based on CHA2DS2-VASc scoring. All adult cardiac surgical patients who underwent left atrial appendage exclusion at our institution were retrospectively studied. Baseline clinical data including age, type of surgery, approach, and CHA2DS2-VASc score were evaluated. The incidence of stroke was calculated at the most recent follow-up. The observed stroke rate was compared to the expected stroke rate base on CHA2DS2-VASc scoring. Between September 2011 and June 2017, 241 patients underwent left atrial appendage exclusion as a stand-alone procedure or with other concomitant cardiac surgical procedures. Two hundred thirty patients (95%) were available for follow-up. One hundred sixty-eight patients (73%) of these patients had the procedure performed minimally invasively either by a right minithoracotomy, upper sternotomy, or via a video-assisted approach. Median age was 72 (range 43–89 years), percent male was 68, median baseline CHA2DS2-VASc was 3. One hundred ten patients (48%) were on oral anticoagulation at the time of follow-up. At an average of 21 months follow-up, the incidence of embolic stroke was 0.9% vs. an expected stroke rate of 5.6% based on their CHA2DS2-VASc (p < 0.05). Various minimally invasive approaches are feasible for left atrial appendage exclusion. These approaches to left atrial appendage exclusion are associated with a reduction in stroke incidence. Randomized, prospective trials may help clarify the benefits of surgical left atrial appendage exclusion. To evaluate early results in prospective randomized controlled trial (RCT) prophylactic pulmonary vein ablation (PULVAB) for coronary artery bypass grafting (CABG). The RCT including 96 patients with coronary artery disease was conducted. There were 3 groups: group 1 (n = 34) was the controlled group of the conventional CABG without ablation. In group 2 (n = 29), conventional CABG was combined with prophylactic pulmonary bipolar radiofrequency ablation (RFA). In group 3, conventional CABG and prophylactic PULVAB were added with the administration of amiodarone in the postoperative period. Concomitant ablation did not lead to the increase of the operation’s main stages’ length. The time of operation was 251 ± 37.7 minutes in group 1, 250.4 ± 42.5 minutes in group 2, and 244.2 ± 29 minutes in group 3 (p = 0.114) and did not differ in the cardiopulmonary bypass time (88.6 ± 19.2; 92 ± 18.4 and 84.8 ± 17.3 minutes; p = 0.08). In-hospital mortality was 0 among the studied groups. Wound complications, bleeding, perioperative myocardial infarction, and stroke were not also noted. Postoperative atrial fibrillation (AF) was registered in 11 (32.4%) patients from the 1st group, in 6 (20.7%) from the 2nd group, and in 2 (6.1%) from the 3rd group. There was no significant difference between groups 1 and 2 (p = 0.298) and also between groups 2 and 3 (p = 0.086). Statistically significant difference was registered between patients from groups 1 and 3 (p = 0.0065), which indicates the effectiveness of the combined methods for preventing AF. AF in 91% of patients occurred at 2–4 days of the postoperative period. Sinus rhythm at discharge was recorded in 97.1% (group 1), 96.7% (group 2), and 97% (group 3), respectively (p = 0.293). There was a tendency to a decrease in the frequency of AF in patients undergoing preventive bipolar RFA of the pulmonary veins. The combination of prophylactic bipolar RFA and amiodarone usage revealed significantly positive results in the postoperative AF prevention. Cryoenergy, together with radiofrequency energy, is the most used method of lesion formation in patients undergoing surgical ablation of atrial fibrillation. Despite its frequent use, the clinical effect of cryoenergy use in endocardial and epicardial approach is unknown. The aim of this study was to compare the effect of different cryoenergy applications on the postoperative incidence of sinus rhythm and the completeness of the lesions performed. A total of 55 patients underwent surgical ablation of atrial fibrillation as part of another cardiac surgery procedure (myocardial revascularization, valve surgery, and combined procedure). The standard protocol of surgical ablation contains isolation of the pulmonary veins and creation of box lesion by cryoenergy under various conditions – epicardially on extracorporeal circulation and cardiac arrest, epicardially on extracorporeal circulation on beating heart, and endocardially. In the postoperative period, patients were invited to electrophysiological examination, where the completeness of surgical ablation lesions was evaluated and completed by catheter ablation if necessary. Twenty-four patients underwent epicardial ablation on the arrested heart (group 1), 12 patients underwent epicardial ablation on the beating heart (group 2), and 19 patients underwent endocardial ablation (group 3). The interval between cardiac surgery and electrophysiological examination was 144 ± 138 days vs. 178 ± 84 days vs. 102 ± 76 days. In the electrophysiological examination, the sinus rhythm was presented in 71% vs. 83% vs. 89% of patients. The completeness of pulmonary vein isolation was confirmed in 31% vs. 25% vs. 95% of patients, complete box lesions then in 15% vs. 0% vs. 79% of patients. Despite the similar clinical effect of surgical ablation in all three approaches, the most morphologically effective use of cryoenergy is endocardial ablation. This approach has a very good result. Our finding further supports the endocardial use of cryoenergy during surgical ablation of atrial fibrillation. We evaluated the outcomes of minimally invasive box-lesion ablation for the treatment of stand-alone atrial fibrillation (AFiB) in our institution. Prospective analysis of 65 patients (mean age of 62.7 years) who were scheduled for bilateral thoracoscopic ablation of either symptomatic paroxysmal (n = 14; 21.5%) or long-standing persistent AFiB (n = 51; 78.5%) from January 2014 to December 2017. The box-lesion procedure comprised bilateral pulmonary veins and left atrial posterior wall ablation using irrigated bipolar radiofrequency. No severe ablation-related complications were observed (bleeding, myocardial infarction, stroke, or death) during in-hospital stay. During 1-year follow-up, sinus rhythm was maintained in 44 patients (67.7%) with no need of antiarrhythmic drug therapy in 42 patients (64.6%). Fourteen patients out of 21 (21.5%) who suffered from after-procedure AFib recurrence underwent endocardial electrophysiological mapping. Completeness of conduction block, which did not require additional catheter ablation, was confirmed in only 4 of those patients (28.6%). Minimally invasive thoracoscopic box-lesion ablation is considered to be a safe and an effective method of stand-alone AFiB treatment. High risk of box-lesion incompleteness in patients with AFiB recurrence in our cohort justifies routine implementation of staged hybrid approach for all patients considering undergoing this procedure. Supported by MH CZ - DRO (FNOl, 00098892). Advantages of del Nido cardioplegia (DNC) over Buckberg cardioplegia (BC) include longer redosing intervals and lower cardioplegia volume delivered. While totally endoscopic robotic cases may derive benefit from having fewer interruptions for cardioplegia administration, adequacy of myocardial protection remains unknown. We reviewed case-matched outcomes of DNC vs. BC in intracardiac robotic patients. From 5/11 to 4/18, 601 consecutive patients underwent robotic intracardiac surgery requiring cardioplegia at a single institution using the daVinciXi Surgical System (Intuitive Surgical, Sunnyvale, CA, USA). Operations were performed via right chest ports without minithoracotomy. After an initial experience with BC (n = 73), we transitioned to DNC in 5/13. We case-matched DNC and BC groups based on age, gender, cross-clamp time, and left ventricular ejection fraction resulting in 66 patients in each group. Parametric and nonparametric tests were used to analyze differences between the case-matched groups. Statistical analysis was performed using SPSS 25 (IBM Corp, Armonk, NY, USA). Mitral repairs accounted for 95% (125/132) of our case-matched operations. Median bypass and cross-clamp time in DNC patients were 115 and 80 minutes, respectively. DNC was associated with less frequent redosing (median number of injections 2 vs. 4, p < 0.001), greater rates of single-injection cardioplegia administration (22.7% vs. 7.6%, p = 0.027), and less cardioplegia volume delivered (median 2,000 vs. 3,100 ml, p < 0.001) ( Table PC17-1 ). DNC and BC had similar rates of antegrade/retrograde (66.7% vs. 69.7%), antegrade only (30.3% vs. 28.8%), and retrograde only (3.0% vs. 1.5%) cardioplegia delivery (p = 0.817). DNC and BC groups had similar salvaged blood utilization (340 vs. 300 ml, p = 0.080), similar postoperative glucose levels (163 vs. 149, p = 0.069), and similar intraoperative blood product utilization (10.6% vs. 9.1%, p = 1.000). Both DNC and BC patients had similar rates of prolonged postoperative inotropic (13.6% vs. 13.6%, p = 1.000) or vasopressor (16.7% vs. 11.4%, p = 0.583) support. There were no 30-day mortalities in either group. Median hospital length of stay (LOS) was 4 days in both DNC and BC patients (p = 0.627). Table PC17-1. Pre-operative variables, intra-operative variables, and outcomes between case-matched robotic patients who received del Nido cardioplegia (DNC) vs Buckberg cardioplegia(BC) BC: Buckberg cardioplegia; BMI: body mass index; CPB: cardiopulmonary bypass; DNC: del Nido cardioplegia; LVEF: left ventricular ejection fraction; NYHA: New York Health Association; XC: cross-clamp. By minimizing the frequency of redosing, DNC allows fewer interruptions for cardioplegia administration than BC. Utilization of DNC did not compromise patient outcomes compared to BC as evidenced by similar rates of prolonged inotropic and vasopressor support, equivalent hospital LOS, and no 30-day mortalities. In minimally invasive cardiac surgery (MICS), the common femoral artery (CFA) cannulation during cardiopulmonary bypass (CPB) could cause limb ischemia (LI). We hypothesize that lack of or poor collateral circulation via the deep femoral artery (DFA) or side branches may be more significant than the size discrepancy in terms of LI. This study evaluates the risk factors of LI in MICS from the point of view of anatomy of the femoral arteries. We performed a retrospective review of 47 patients who underwent MICS without prosthetic graft conduit for femoral arterial cannulation between January 2014 and August 2017 at our institution. Regional oxygen saturation (rSO2) of both lower extremities was monitored during the operation by INVOS®. The diameters of CFA, superficial femoral artery (SFA), and DFA were measured using preoperative computed tomography. Based on those diameters and the presence or absence of side branches that can have collateral circulation, we divided them into the following 4 anatomical types (type A: DFA > SFA without branch, type B: DFA < SFA with side branch in CFA, type C: DFA < SFA with side branch in bifurcation of SFA and DFA, type D: DFA < SFA without side branch). We used maximum value of postoperative creatine kinase (CKmax) as the index of postoperative LI. To exclude the influence of each muscle mass, CK divided the area of muscles of femoral regions and it is defined as CK/MA. The predictors for LI, including age, sex, body surface area, body mass index, CPB time, the diameter of CFA, SFA, and DFA, remaining lumen size of CFA after the cannulation, the anatomical types of femoral artery, and the baseline and the drop rate from the baseline of rSO2 of lower extremities, were analyzed. No critical LI occurred in 47 patients. In the anatomical type of femoral artery, type A was the most numerous (type A: 27 [57%] legs, type B: 5 [11%] legs, type C: 3 [6%] legs, type D: 12 [26%] legs). In this cohort, the median CKmax was 1973 U/l (1,293–2,894) and the median CK/MA was 15.6 U/l/cm2 (9.9–20.1). In multivariate analysis of CK/MA >20, anatomical type D was the only predictor (odds ratio 7.188; 95% confidence interval: 1.023–50.506, p = 0.0047) and the remaining lumen size of CFA after the cannulation and the drop rate of rSO2 were not predictors. Our result suggested that anatomical type D was a risk factor for LI in MICS. In type D cases, attention should be paid to the choice of the cannulation site. Acute cardiogenic shock is associated with high mortality rates. The Impella device is a microaxial left ventricular assist device that can be inserted through the axillary artery. The purpose of our study is to determine the role of the axillary Impella devices on patients with acute cardiogenic shock. A retrospective chart review was conducted to identify patients who underwent Axillary Impella device placement for acute cardiogenic shock from January 1, 2014 to September 30, 2018 at a single institution. In-patient records were examined to determine the duration of device, length of stay (LOS), postoperative complications, and 30-day in-hospital mortality. A total of 40 patients, who were primarily men (N = 29) with a mean age of 61.2 ± 10.7 years, underwent Axillary Impella placement for cardiogenic shock. The primary reasons for implant were (1) requirement of upgraded support from an Impella CP or intra-aortic balloon pump (IABP) to Impella 5.0, (2) to treat left ventricular (LV) distention for patients on extracorporeal mechanical oxygenation (ECMO), and (3) to provide longer-term support and allow for mobilization of the patients. Twenty-three of the patients had previous devices already in place including a femoral Impella CP device or an IABP and 9 patients were on ECMO support. The duration of the device was 21.05 ± 17 days with the LOS of 40.8 ± 28 days for those patients. Seventeen of the patients went on to additional surgery including (1) Heartmate 3 device placement (N = 6), (2) other cardiac procedures such as surgical revascularization (N = 9), and orthotopic heart transplantation (N = 2). A total of 21 patients of the 40 (52%) died during hospitalization with 7 patients (17%) having complications related to the Impella device. These complications included right arm ischemia or neuropathy (N = 3) and Impella malfunction requiring device replacement (N = 4). The majority of these devices were placed in the right axillary artery (N = 38) vs. the left axillary artery (N = 2). A total of 58% (N = 23) of the study patients had previous mechanical support and 23% (N = 9) were on ECMO demonstrating the severity of disease and accounting for the high mortality. The Axillary Impella device allows for a minimally invasively placed device that is durable with a mean duration of 3 weeks. The Axillary artery Impella 5.0 provides upgraded full cardiac support while allowing for mobilization of the patient. In addition, it treats LV distention in patients on ECMO while avoiding sternotomy. Finally, the Axillary Impella provides time for decision making for additional therapy with either long-term devices or orthotopic heart transplant. Therapy of severe pulmonary embolism (PE) in patients immediately after surgery poses a difficult challenge with regard to bleeding complications. Ultrasound-accelerated thrombolysis (USAT) has proven to be an effective therapy for severe PE using a fraction of conventional lysis doses. In this case series, we present 3 cases with severe PE immediately after surgery treated by ultra-low-dose USAT. Between June and October 2017, 3 patients (2 male, 60 and 61 years old; 1 female, 16 years old) with symptomatic massive PE early after surgery were presented to our interdisciplinary PE response team where ultra-low-dose USAT was decided to be applied due to the extent of PE and previous surgery in all patients. The patients were fitted with 2 EKOS® 12 cm devices (BTG Ltd, Surrey, UK) in each respective pulmonary artery across the occlusive thrombi for 6 hours receiving 1 mg rt-PA/h/catheter. Transthoracic echograms and computed tomography (CT) scans were performed before and within 48 hours of therapy initiation. All 3 patients survived USAT uneventful with minor bleeding receiving a total dose of 12 mg rt-PA per patient. Within the first hours of therapy significant reduction of RV/LV ratio (1.3 ± 0.2 vs. 0.7 ± 0.08, p: 0.043) and mean pulmonary arterial pressure (33.4 ± 6.1 mmHg vs. 21.7 ± 3.2 mmHg, p: 0.021) as well as significant increase of oxygen saturation on room air (O2 sat, 83.6 ± 4.1 vs. 99.3 ± 1.1, p: 0.012) and right ventricular peak systolic strain rate (−1.12 ± 0.07 s−1 vs. −1.37 ± 0.05 s−1, p: 0.011) was observed. Notable reduction of heart rate, systolic pulmonary arterial pressure, and longitudinal peak systolic strain, and an increase in tricuspid annular plane systolic excursion and tricuspid annular systolic velocity were also documented (Table PC20-1). Follow-up CT scans revealed only minor remaining nonobstructive thrombi. Table PC20-1. Table PC20-1. In this case series, ultra-low-dose USAT resulted in nearly complete resolution of thrombus within 6 hours of therapy with very rapid recovery of hemodynamics in these highly symptomatic patients. Thus, ultra-low-dose USAT appears to be a safe and reasonable therapy option for early postoperative PE. Femoral artery perfusion represents a standard cannulation approach in minimally invasive mitral valve surgery, while several limitations due to retrograde aortic perfusion exist. Antegrade arterial flow through the axillary artery has theoretical advantages as compared to the retrograde femoral approach, which have to be confirmed yet in the clinical setting. We aimed to compare the postoperative outcomes of axillary artery perfusion vs. retrograde femoral perfusion in the minimally invasive mitral valve surgery setting. We systematically analyzed the outcomes of 46 consecutive patients who underwent minimally invasive mitral valve surgery between 2016 and 2018 using the arterial cannulation of right axillary artery (group A) due to severe aortic arteriosclerosis. Perioperative outcomes of the study group were compared with a historical control group of retrograde femoral perfusion (group F), which was adjusted for age and gender (n = 46) according to the propensity score matching. Primary endpoint of the study was in-hospital mortality and perioperative cerebrovascular events. Perioperative risk score values were significantly higher in group A compared to group F (EuroSCORE II: 3.99 ± 2.57 vs. 1.67 ± 1.58; p = 0.001; Society of Thoracic Surgery score: 2.19 ± 1.49 vs. 1.31 ± 0.64; p = 0.023). Cardiopulmonary bypass time (group A: 172 ± 46; group F: 178 ± 51 minutes; p = 0.627) and duration of surgery (group A: 260 ± 65; group F: 257 ± 69 minutes; p = 0.870) were comparable in both groups. However, aortic cross-clamp time was significantly shorter in group A as compared to group F (86 ± 20 vs. 111 ± 29 minutes; p < 0.001). There was no perioperative stroke in both study groups. In-hospital mortality was comparable in both groups (p = 0.495). In group A, 1 patient required median sternotomy and central aortic repair due to intraoperative aortic dissection. No major cardiovascular events occurred in group A, despite significantly increased perioperative risk profile. Right axillary artery perfusion is a safe and reproducible technique in an elderly cohort of patients undergoing minimally invasive mitral valve surgery who present with the signs of systemic atherosclerosis. Given the appropriate institutional expertise in minimally invasive mitral valve surgery, high-risk patients with severe arteriosclerosis can be safely treated via the minimally invasive approach using antegrade arterial perfusion. Acute biventricular failure poses a unique challenge due to the morbidity associated with conventional support techniques, such as venoarterial extracorporeal membrane oxygenation (VA ECMO). Recent developments in percutaneously inserted right and left ventricular support devices have made these minimally invasive options useful in acute failure. Biventricular percutaneous support in the adult population for treatment of acute cardiogenic shock has not been reported yet. Here we present our early experience with this technique. A retrospective review of a prospectively collected database was performed for all patients receiving biventricular percutaneous support from March 2018 to December 2018. Inclusion criteria were patients suffering acute cardiogenic shock and who received concomitant percutaneous biventricular support. This support was provided via a right ventricular support device (RVAD) inserted in the right internal jugular vein combined with a left ventricular support device (LVAD) inserted in the right subclavian artery. Primary endpoint was patient survival to device explant. Patient characteristics, pre- and postoperative variables, and short-term outcomes were collected with a focus on patient hemodynamics and device-related complications. Four patients met inclusion criteria age 20–75 (median 59). Etiologies of heart failure included viral cardiomyopathy (n = 1), acute ischemic heart disease (n = 2), and post-cardiotomy biventricular failure (n = 1). Median preoperative cardiac index was 1.8 l/min/m2 (range 1.5–2.6), with a median cardiac output of 3.8 l/min (2.9–6.7). Ejection fraction was 5%–60% on inotropic support, with a median preoperative vasoactive inotrope score (VIS) of 32.1 (18–43.8). Patients normalized their preoperative lactic acidosis after a median of 3 hours and were noted to have a median immediate postoperative reduction in VIS of 12.2 (1–23.1, Figure PC22-1 ) after device implantation. Patients received biventricular support for 5.5 days (range 1–11). Two patients survived to device explant, with no patient suffering device-related stroke, pulmonary emboli, valvular injury, or bleeding requiring reintervention. Figure PC22-1. Vasoactive Inotrope Score Prior and After Implant. VIS: vasoactive inotrope score. Combined percutaneous RVAD and LVAD implantation can successfully be employed as a stand-alone therapy, or as a bridge to further treatment in patients with cardiogenic shock. This novel technique warrants further investigation and refinement, and can potentially offer a rapidly deployed minimally invasive alternative to VA ECMO in select patients. Patients with acute mitral valve regurgitation (MR) presenting with cardiogenic shock have a high risk of mortality. Preoperative stabilization may improve overall patient survival. The purpose of this study is to evaluate the application of the transcatheter mitral valve repair system in patients with acute severe MR and cardiogenic shock. From 2014 to 2018, 6 patients underwent MitraClip placement for acute MR and cardiogenic shock. The median age was 83 years (range 73–89). Five patients (83%) were female. Three patients (50%) had a prior myocardial infarction. Five patients (83%) had severe and 1 patient (17%) had moderate MR prior to MitraClip implantation. Three patients (50%) had ejection fraction below 40% (median 42%, range 28%–65%). Four patients required preoperative left ventricular assist device placement to support their left ventricular function. Transcatheter mitral valve repair system was implanted at a median 6.5 days (range 0–17 days) from admission. Post procedure, 4 patients (66%) had mild MR and 2 (44%) patients had moderate MR. The median duration of ventilatory support was 3.3 days (0–35.8 days). Thirty-day mortality was 33% (2 patients). One patient had mitral valve replacement 6 months after MitraClip implantation for severe recurrent MR. The transcatheter mitral valve repair system may decrease mortality in critically ill patients presenting with acute mitral regurgitation and cardiogenic shock and avoids emergency surgery owing to successful acute stabilization. Myocardial bridges (MBs) are a congenital coronary variant in which contractile myocardium overlies a coronary artery. Patients with hemodynamically significant MBs of the left anterior descending (LAD) coronary artery may present with debilitating angina despite optimal medical therapy. We previously demonstrated that surgical MB unroofing via sternotomy significantly improves symptoms and quality of life. We hypothesized that minimally invasive MB unroofing could achieve similar results. Adult patients (n = 101) who underwent LAD MB unroofing at our institution between November 2011 and December 2018 were included. MBs were characterized by coronary angiography and intravascular ultrasonography. Hemodynamic significance was determined by diastolic fractional flow reserve (dFFR) measured distal to the MB. Surgical unroofing was performed via sternotomy (n = 72, 2011–2018) or left anterior minithoracotomy (n = 29, 2016–2018). The primary outcome was symptom status assessed by Seattle Angina Questionnaire (SAQ) before and 6 months after surgery. Secondary outcomes included surgery duration, length of hospital stay, and incidence of postoperative complications. There were no significant differences in baseline patient characteristics between the groups. Patients were young (sternotomy 45.5 [36.5–58.0] years, mini 54.0 [39.0–57.0] years) and mostly female (sternotomy 58.3%, mini 51.7%). All patients were symptomatic. MB lengths were comparable (sternotomy 2.87 [2.07–4.62] cm, mini 2.84 [2.16–3.60] cm), although dFFR was lower in the mini group (0.59 [0.53–0.68] vs. 0.67 [0.57–0.73], p = 0.036). While all minithoracotomy cases were performed off-pump, 51.4% of sternotomy cases were performed with the heart arrested on cardiopulmonary bypass. The mini group experienced a shorter surgery duration (134 [120–149] minutes vs. 162 [134–216] minutes, p = 0.001) and shorter hospital stay (3 [3–4] days vs. 4 [4–5] days, p = 0.001). There were no occurrences of death, myocardial infarction, or stroke in either group. The mini group experienced no blood transfusions or surgical wound infections, whereas these occurred in 4.2% and 2.8% of sternotomy cases, respectively. SAQ scores improved significantly after mini MB unroofing with regard to physical limitation, anginal stability and frequency, treatment satisfaction, and quality of life ( Figure PC25-1 ). Figure PC25-1. Graphical presentation of preoperative (orange) and 6-month postoperative (blue) seattle Angina Questionnaire scores for patients who underwent minimally invasive myocardial bridge unroofing. Data are presented as median [interquartile range]. Dots indicate median; boxes indicate interquartile range. P-value <0.05 was considered statistically significant. In selected patients, minimally invasive MB unroofing is safe, expedites recovery compared to a sternotomy approach, and provides significant improvements in symptoms and quality of life. The da Vinci Xi surgical system (Intuitive Surgical, Sunnyvale, CA, USA) cannot give tactile feedback to surgeons. This shortcoming may increase the risk of left internal thoracic artery (LITA) injury during its harvest. We utilized Firefly® Fluorescence Imaging (Firefly) to assess LITA quality in robot-assisted minimally invasive direct coronary artery bypass (R-MIDCAB). We retrospectively reviewed clinical records and intraoperative video of 30 patients who underwent R-MIDCAB with LITA-left anterior descending (LAD) coronary bypass. All patients had postharvest assessment of LITA blood flow by Firefly with 1 ml (2.5 mg/ml) of indocyanine green injection through a central line. Twenty-seven of the patients were male, mean age was 67.7 ± 10.7 (SD) years. In postharvest assessment performed before transection of the distal LITA, blood flow in LITA was well visualized in 28 patients. In the remaining 2 patients, one had dissection and the other had severe spasm of the LITA. Firefly was also useful for locating LITA and LAD and for assessing blood flow of the graft after anastomosis. Time required for each Firefly assessment was approximately 20 seconds. There were no side-effects or complications due to Firefly intra- and postoperatively. Twenty-six patients had postoperative coronary computed tomography; LITA patency rate was 100% (26/26). Firefly is fast, simple, and effective for locating and assessing flow in LITA and LAD before and after anastomosis in R-MIDCAB. The ideal blood salvaging strategies for off-pump coronary artery bypass graft procedures have not been determined. We developed a new blood salvaging system that uses a cardiotomy suction. The purpose of this study was to examine the efficacy of this novel method. This was a retrospective study involving 100 consecutive patients undergoing off-pump coronary artery bypass grafting from June 2015 to July 2018 in our hospital. In 50 patients, a simple cardiotomy suction system was used (cardiotomy suction group). These individuals were compared with 50 historical cohorts who were treated with the conventional cell saver system (cell saver group). There was no significant difference in the patient’s background. There was no in-hospital mortality in either group. The patients who received a blood transfusion were significantly fewer in the cardiotomy suction group (cardiotomy: 22%; 11/50 vs. cell saver: 44%; 22/50, p = 0.03). The cardiotomy suction group tended to have received fewer transfused red blood cells (cardiotomy: 0.85 ± 2.1 units vs. cell saver: 1.44 ± 2.4 units, p = 0.18). The postoperative serum total protein and albumin levels were significantly higher in the cardiotomy group. As there was concern about kidney injury due to crushed erythrocyte because it had not been removed in the cardiotomy suction group, there was no significant difference about the rate of change in serum creatinine level and the postoperative amount of urine. Our newly developed simple cardiotomy suction system, when compared with the conventional cell saver system, produced similar clinical results and attenuated postoperative hemodilution. Our system may emerge as a preferable alternative for blood salvage during off-pump coronary artery bypass grafting. Figure PC27-1. Minimally invasive approaches for graft procurement are associated with excellent outcomes in terms of morbidity and patients’ discomfort, thus without affecting graft quality, patency rate, and long-term outcomes in patients undergoing coronary artery bypass grafting (CABG) surgery. We aim to extensively describe the technique for endoscopic radial artery (RA) and saphenous vein (SV) harvesting using non-sealed approach for grafts procurement during CABG surgery. All patients scheduled for coronary artery bypass surgery can potentially benefit of an endoscopic approach when the use of RA and/or SV is planned. In this video, endoscopic harvesting of RA and SV was performed by means of nonsealed system. Nonsealed systems do not require active carbon dioxide insufflation; however, CO2 may be used as a visual flush without any occlusive port at the entry point; thus, adoption of a nonsealed approach encompasses any potential drawbacks of active CO2 insufflation. Endoscopic harvesting for RA and SV showed similar macroscopic results when compared to “open” techniques. Microscopically, structural and functional viability of the endothelium and vasoreactivity are preserved after endoscopic harvesting. Detrimental effects were demonstrated on functional and structural properties of the SV and RA and such changes are significantly higher when a “sealed system” approach is used. Minimally invasive techniques demonstrated significant better outcomes in terms of incidence of wound and neurological complications as well as patients’ satisfaction when compared to “open” techniques for graft harvesting. Harvesting-related pain and discomfort, mobility, and sensory disfunction are significantly less relevant after minimally invasive conduit harvesting. In conclusion, increasing evidences support the use of endoscopic approaches for graft procurement and such techniques showed to be safe and effective with comparable results in terms of graft quality and cardiac-related adverse events but a significantly superiority in terms of complications and patients’ satisfaction when compared to open approaches. Post-pericardiotomy syndrome has been reported in 10%–40% of all cardiac surgery patients. In spite of a lower incidence of this syndrome in patients undergoing sternal-sparing surgery, we continue to observe it in our beating-heart totally endoscopic coronary bypass (TECAB) patients. The aim of this study is to evaluate if a 6-day steroid taper after TECAB would decrease the incidence and manifestations of post-pericardiotomy syndrome. This retrospective study evaluated the outcomes of 100 patients undergoing single- and multivessel TECAB from January 2017 to October 2018 in our center. We compared postoperative outcomes of 100 patients who did and did not receive a postoperative steroid taper. STATA software was used to evaluate the effect of steroids on each outcome of interest using multiple linear regression for continuous outcomes and logistic regression for binary outcomes. During the study period, the “steroid group” (n = 50) was given 100 mg of intravenous (IV) hydrocortisone intraoperatively and a 6-day oral methylprednisolone taper starting on postoperative day 1 with 24 mg. The control “non-steroid group” (n = 50) did not receive any postoperative steroids after the initial intraoperative IV dose. The groups were similar with respect to gender, age, number of vessels bypassed, Society of Thoracic Surgery risk, and operative time. Although mean intensive care unit and hospital lengths of stay trended shorter in the “non-steroid” group and the number of patients diagnosed with postoperative pericarditis was lower (1.08 days vs. 1.44 days, p = 0.094, and 2.6 days vs. 3.2 days, p = 0.062, and 2 patients vs. 6 patients, p = 0.099 respectively), none of these outcomes reached statistical significance. Average pain scores and postoperative complications (including atrial fibrillation, pericardial effusion, pleural effusion, stroke, acute renal failure, myocardial infarction, readmission, and mortality) showed no significant differences between the groups. Average chest tube drainage was lower and mean glucose level was higher on the first postoperative day in the “steroid group” (105 ml vs. 205 ml, p = 0.009 and 169 vs. 147, p = 0.007, respectively). In this pilot study of patients undergoing beating-heart TECAB, we found a trend of shorter lengths of stay and a decreased incidence of clinical post-pericardiotomy syndrome when postoperative oral steroids were given. Further larger studies are warranted. Table PC29-1. Table PC29-1. The robotic-assisted minimally invasive coronary artery bypass (MIDCAB) consists of facilitating the endoscopic harvesting of the left internal mammary artery. As many centers are increasingly implanting minimally invasive programs, we sought to evaluate the impact of the learning curve on early outcomes following robotic-assisted MIDCAB. From 2006 to 2018, 236 consecutive robotic-assisted MIDCAB procedures were performed, representing the entire inaugural experience. The cohort was divided into 2 consecutive periods of 118 patients according to the period of surgery (P1 and P2). Efficiency endpoints included surgery and coronary occlusion duration, and safety included mortality and major morbidity. A cumulative sum (CUSUM) analysis was performed for a composite endpoint including early mortality, reintervention for bleeding, prolonged intubation, stroke, myocardial infarction, hemofiltration, and urgent conversion. The expected major complication was set at 10%. There were 2 operative mortalities (0.8%). In terms of safety, there was no difference in the incidence of major complications between the two periods (P1: 13 [11%] and P2: 9 [8%]; p = 0.37). The CUSUM analysis showed that the rate of major complications remained constant during the study period. In terms of efficiency, there was a statistically significant improvement of surgery duration after the first period (P1: 2.5 [1.6–5.5] hours vs. P2: 2.2 [1.6–5.3] hours; p = 0.01). However, the duration of the coronary occlusion was similar across the two study periods (P1: 9.5 ± 4.3 minutes vs. P2: 8.8 ± 2.9 minutes). The median length of hospital was similar between the 2 periods (5 [1–33] days). In conclusion, there is no significant impact of the learning curve on early complications following robotic-assisted MIDCAB. However, surgery duration improves over time. Figure PC30-1. CUSUM: cumulative sum. No-touch (NT) saphenous vein (SV) harvesting preserves the adventitial vaso vasorum, prevents medial ischemia, and is associated with an improved short- and long-term vein graft patency. However, the wound complications after NT-SV harvesting are reported to be more significant than the associated skeletonized technique. The majority of the complications are caused by thermal injury resulting from the use of heat-generating monopolar electrocautery. The superficial inguinal lymph nodes and large lymph vessels accompany the SV anatomically and are prone to damage during the harvesting, which may also be associated with a higher rate of the complications. The electrothermal bipolar vessel sealing device (EBVSD) has been designed to aid in coagulation and dissection with less thermal spread than conventional electrocautery. We introduced EBVSD to NT-SV harvesting thorough mini-incisions, considering the ability of this method to firmly seal the lymphatic vessels. The aim of this study was to clarify whether EBVSD contributed to the feasibility of this minimal NT-SV harvesting. After anesthetic induction, ultrasonography mapping was performed to assess the course and quality of SV. Some surgical instruments have been devised to facilitate with small incisions. Through small incisions made at levels of upper thigh, knee, and ankle, a cordless retractor with a built-in LED light source was inserted to enhance the visualization of the operating field and brightens up the operating field. The SV was harvested with a pedicle of surrounding tissue of about 5 mm attached to the main trunk of the SV using EBVSD. Due to the lack of smooth muscle cells in the wall of lymphatic vessels, and a lack of thrombocytes in lymphatic fluids, it was attempted to seal the surrounding connective tissue together with the lymphatic vessels to reinforce the sealing effect. NT-SV was harvested successfully without any complications through mini-incisions. After insertion of a 15 Fr round silicone drain in the SV harvest site, the skin is closed with running suture with absorbable monofilament suture without postoperative complications. This technique is highly possible and could have certain vessels sealing and improved workability and postoperative outcome. Further research is required to refine technology and techniques. Off-pump myocardial revascularization allows improved short-term results of coronary surgery regarding mortality and neurological outcome. Still, there is limited data about the long-term major adverse cardiac and cerebral events (MACCE) results in large cohort studies with long-term follow-up. This study demonstrates those results of more than 3,000 patients. Between 2006 and 2012, 5,915 patients received an isolated coronary artery bypass grafting procedure in our department. We excluded all patients receiving an emergency or redo procedure and patients operated via left-sided minithoracotomy. Of the remaining 3,217 patients, 2,337 were operated off pump and 880 on pump. All patients were interviewed regarding survival, repeat revascularization, recurrence of angina, and MACCE rate. The perioperative data did not differ between the two groups. During the long-term follow-up a significant advantage for the off-pump coronary bypass (OPCAB) technique was found regarding cerebrovascular stroke and survival (Table PC32-1). Table PC32-1. Table PC32-1. Although the OPCAB technique is described as more demanding for the surgeon compared to the on-pump revascularization, patients operated off-pump show a significant benefit regarding long-term survival and interestingly late-onset of cerebrovascular stroke. Outcomes of the Florida Sleeve (FS) procedure in patients with bicuspid aortic valve (BAV) have not been reported before. We compared outcomes of the FS procedure in patients with BAV vs. those with trileaflet aortic valve (TAV). From May 2002 to January 2018, 177 patients including 18 BAV and 159 TAV underwent the FS procedure. Baseline characteristics, perioperative outcomes, ventricular dimensions, ejection fraction, and degree of aortic insufficiency were compared between the two groups. Kaplan–Meier analysis evaluated survival and freedom from reintervention. Mean ± standard deviation of age and aortic root diameter were comparable in BAV and TAV groups, 47.83 ± 11.19 vs. 49.59 ± 15.79 years (p = 0.55) and 56.57 ± 6.18 vs. 55.17 ± 8.84 mm (p = 0.46), respectively. Thirteen (72.22%) patients in the BAV group and 115 (72.33%) patients in the TAV group were male (p = 0.85). Left ventricular end-systolic and -diastolic diameters decreased from baseline to 1 week in BAV group (p = 0.037 and 0.12). Left ventricular end-diastolic diameter improved at both 1 week (p < 0.001) and 30-day (p = 0.001) in the TAV group (Table PC33-1). The 30-day mortality and stroke rates were zero in the BAV group and 1.88% in the TAV group (p = 1.0). One patient (5.55%) in the BAV group and 8 (5.03%) patients in the TAV group needed permanent pacemaker implantation (p = 0.62). Freedom from reoperation was 93% at 1–8 years in the BAV group and 100% at 1 and 2 years and 99% at 3–8 years in the TAV group (p = 0.041). Patients’ survival rate was 100% at 1–8 years in the BAV group and 97% at 1 year, 96% at 2–5 years, and 91% at 6–8 years in the AV group (p = 0.42). Freedom from aortic insufficiency greater than mild was 93% in the BAV group and 96.5% in the TAV group at 5 years. Table PC33-1. Comparison of Outcomes Between Bicuspid and Tricuspid Aortic Valve Patients After the Florida Sleeve Procedure Table PC33-1. Comparison of Outcomes Between Bicuspid and Tricuspid Aortic Valve Patients After the Florida Sleeve Procedure This is the first report to examine outcomes of the FS procedure in patients with BAV. This technique is feasible and the results appear durable when compared to patients with TAV. To assess the degree of oversizing with the Perceval sutureless valve at the time of implantation and related short-term outcomes including post-implantation gradients, paravalvular leak, and requirements for a permanent pacemaker. Fifty-five consecutive patients scheduled for elective aortic valve replacement were imaged with a cardiac computed tomography angiography. Detailed measurements of the left ventricular outflow tract, aortic annulus, and sinuses of Valsalva were obtained and compared against the implant size. The degree of oversizing was calculated as a percentage using the perimeter of the fully expanded valve size and the annular perimeter. Hemodynamic data from postoperative echocardiography, requirement for permanent pacemaker, and mortality within 30 days were recorded. The sizing ranged from 33% undersizing to 36% oversizing. On average the valve/annulus perimeter ratio was 0.96. Two of 55 patients had trace paravalvular leak (PVL) (3.6%, 0.4%–12.5%). The ratio in these 2 patients was 0.97 and 0.67 (the most undersized prosthesis). Four patients required a permanent pacemaker (7.2%, 2%–17.5%). The ratio in these 4 patients was between 0.86 and 1.36. There was no mortality at 30 days and the average post-implantation gradient was very low at 7.9 mmHg (range 2–14). This study reports the extent of under- and oversizing of a sutureless, surgically placed aortic bioprosthetic valve that has strong similarities with a transcatheter aortic valve replacement (TAVR) valve. In contrast to TAVR, where oversizing is pursued deliberately, our data suggest that oversizing is not required with the Perceval valve. Even with slight undersizing, in reference to the annular diameter, PVL is not commonly seen. On the other hand, oversizing may result in higher pacemaker rates and higher gradients because of restricted leaflet motion. Aortic valve replacement through a right minithoracotomy is a minimally invasive procedure not frequently used because of having been reported longer cardiopulmonary bypass and cross-clamping times compared to the standard full sternotomy. We reviewed 634 patients (350 male 55% with median age of 75; range 16–93 years) who received an aortic valve replacement between January 2010 and April 2018 through a right minithoracotomy. A total central cannulation was preferred in more than 90% of patients. The majority received an aortic valve replacement with a pericardial bioprothesis sutured using three 2/0 prolene running sutures or more recently a sutureless prosthesis (80 patients; 12%). Mean prosthesis size was 24 mm. Aortic replacement was performed through a 4–6 cm skin incision at the third intercostal space. Six patients were a REDO case. Overall median cardiopulmonary bypass and aortic cross-clamping time was, respectively, 58.5 minutes (range 25–172) and 46 minutes (range 16–134). Median ventilation time and intensive care stay were 7 and 44 hours. Patients transfused were 42%. Hospital mortality was 1.4% (9/634). This single-center experience shows that aortic valve replacement achieved through a right minithoracotomy is a safe procedure with excellent results. Thanks to a standardized technique, cardiopulmonary bypass and cross-clamping times comparable with the standard can be obtained and peripheral cannulation avoided. The implementation of a multidisciplinary patient blood management (PBM) program may contribute to a reduction in transfusion requirements, a decrease in health costs, and an improvement in patient outcomes. We compared 2 different time intervals of aortic valve replacement (via conventional and minimally invasive techniques) under different strategies of blood management. This retrospective cohort study included high-risk patients (Euroscore II >5) undergoing aortic valve surgery under different PBM strategies during the period from January 2011 until November 2018 ( Table PC36-1 ). Patients were matched for age, gender, body mass index, and Society of Thoracic Surgery score: group 1 (control): (2011–2014) N = 294 and group 2: (2015–2018) N = 277. Table PC36-1. Components of Patient Blood Management Strategies Within Years IV: intravenous; PBM: patient blood management; SAVR: surgical aortic valve replacement. The percentage of patients who received transfusion was 14.3% in group 2 and 34.6% in control (p < 0.05). Postoperative hemorrhage (group 2: 220 ± 30 and 775 ± 60 ml in control; p = 0.012), respiratory support duration (8.3 ± 2/16.7 ± 2 hours; p = 0.011) and intensive care unit stay (1.03 ± 1 vs. 2.6 ± 1.1 days, p = 0.025) were significantly better in group 2 vs. control. No difference in mortality and major complications were noted. Stepwise multiple logistic regression analysis demonstrated minimally invasive surgery (odds ratio [OR]: 5.1), minimally invasive extracorporeal circuitry (OR: 3.66), and cardioplegia type (OR: 3.2) as leading independent predictors of the reduction in transfusion. Cost analysis demonstrated 11.9% decrease in group 2 with respect to group 1 (p = 0.035). Based on the available evidence, PBM protocols are likely to be most productive for high-risk cardiac patients. The extent is in significant progress introducing minimally invasive techniques and circulation. Studies with higher patient population are still warranted. Although conclusive data compared to conventional surgery are still lacking, minimally invasive surgery is rising in proportion. This study aimed to provide a contemporary, risk-adjusted comparison of early postoperative outcomes of aortic valve replacement through a full sternotomy (CAVR) or upper ministernotomy (MIAVR). Between January 2014 and June 2018, 297 patients underwent primary, elective, isolated aortic valve replacement. Early postoperative outcomes were compared among 2 propensity-matched groups of 120 patients who had MIAVR or CAVR. Our MIAVR technique relies on 4 principles: (1) very limited skin incision and upper ministernotomy preserving the xiphoid process; (2) central aortic cannulation in order to provide anterograde arterial flow; (3) percutaneous, ultrasound, and radioscopic-guided common femoral vein cannulation; and 4) percutaneous, ultrasound, and radioscopic-guided pulmonary artery and coronary sinus cannulation for left heart venting and retrograde cardioplegia delivery, respectively. MIAVR patients had longer cardiopulmonary bypass (109 ± 26 vs. 100 ± 24 minutes, p = 0.01) and operative times (254 ± 39 vs. 226 ± 37 minutes, p < 0.001). However, aortic cross-clamp times were comparable (75 ± 22 vs. 79 ± 18 minutes for MIAVR and CAVR, respectively, p = 0.12). Overall, conversion rate was 1.7% (2 patients). MIAVR patients had less blood loss during the first 24 hours (253 ± 204 vs. 323 ± 296, p = 0.03), less red blood cell transfusions (1.4 packs [1.1–1.9] vs. 2.1 packs [1.8–2.7]), and shorter assisted ventilation time (7.1 ± 3.3 vs. 9.7 ± 3.8 hours, p < 0.001) when compared to CAVR patients. These results led to a significantly shorter intensive care unit and hospital stay for MIAVR patients (2.5 ± 1.3 vs. 3.4 ± 1.1, p < 0.001 and 6.9 ± 4.1 vs. 8.2 ± 4.8, p = 0.03, respectively) ( Figure PC37-1 ). All other postoperative outcomes were comparable between groups. Figure PC37-1. Hybrid aortic valve replacement through upper ministernotomy significantly reduced 24 blood loss (A) and postoperative red blood cell transfusions (B). Moreover, mechanical ventilatory support was suspended faster for these patients (C). Overall, minimally invasive aortic valve replacement was associated with significantly shorter ICU and hospital stays than the conventional approach (D). CAVR: conventional aortic valve replacement; ICU: intensive care unit; MIAVR: minimally invasive aortic valve replacement. MIAVR provides early postoperative outcomes at least comparable to CAVR. Moreover, it might reduce transfusions, postoperative bleeding, and assisted ventilation time quickening patient recovery. This could be of paramount importance in the elderly and frail patients. Right anterior minithoracotomy for surgical aortic valve replacement (SAVR) is effective and with excellent outcomes. We believe this approach might be safe and effective even in those patients with intermediate surgical risk (4% < Society of Thoracic Surgery [STS] risk score < 8%) and severe calcified aortic stenosis, ideally suitable for transcatheter aortic valve implantation procedures in the PARTNER 2 Trial setting. Retrospectively, from January 2010 to June 2018, we collected 102 consecutive adult patients with intermediate surgical risk, undergoing isolated SAVR for tricuspid severe aortic stenosis. Minimally invasive aortic valve replacement was performed by a single surgeon, through a 4–6-cm-long RAT at the third intercostal space without rib avulsion or ligation of the right internal mammary artery. As our standard setting, we perform a complete central cannulation with normothermic systemic perfusion and blood-based cardioplegia. All procedure went successfully. Complete central cannulation (arterial = distal ascending aorta, vein = atrial appendage) and RAT approach have been used in all cases. Baseline characteristics: male 36.36%; mean age of 83.4 ± 3.8 years; mean STS risk score of mortality 4.81% ± 0.71% (range 4.02%–6.83%) and of morbidity/mortality 24.57% ± 4,65%. Results: median implanted prosthesis diameter was 23 mm; mean cardiopulmonary bypass (CPB) duration was 49.3 ± 14.9 minutes; aortic cross-clamping time was 36.8 ± 14.7 minutes; median ventilation time was 6 hours; median intensive care unit stay 2.5 days. Observed mean bleeding rate in the first 12 hours was 476 ± 230 ml, 37.5% patients needed blood transfusion (median number of bags: 2). Pacemaker implantation rate was 2.17%. The total in-hospital stay median duration was 7 days. Observed 30-day mortality rate was 1.96%, and observed morbidity/mortality rate was 9.3%. No paravalvular aortic regurgitation more than mild at discharge was observed. Results show that our approach is safe and effective for surgical aortic valve replacement in intermediate-risk patients. RAT approach is a valid option in this subset of patients to avoid the most common complications after transcatheter aortic valve replacement procedure. Complete central cannulation is safe, avoiding the risk of peripheral CPB implantation with no impact on perioperative mortality. No-rib-spreading and video-assisted right anterior minithoracotomy aortic valve replacement (AVR) is an approach that is currently adopted by centers experienced in right anterior minithoracotomy aortic valve surgery. The effort of this endoscopic AVR collaborative group is to analyze results of AVR performed with the lowest degree of invasiveness, by trained teams and in low- and intermediate-risk patients. This is a multicentric retrospective study with a prospective data collection protocol. Centers, with surgeons who have an experience of at least 20 AVRs performed through right anterior minithoratotomies with the use of a rib retractor, were contacted to include patients in the study. Main technical features of the protocol are avoidance of a rib retractor and exclusive use of a soft tissue retractor with a limited skin incision (<6 cm); use of femoro-femoral peripheral cardiopulmonary bypass (CPB); use of fiberoptics introduced laterally to the minithoracotomy (2nd space); carbon dioxide insufflation and transesophageal echocardiogram for perioperative monitoring; use of sutureless or rapid-deployment or sutured valve prosthesis with or without automated knotting devices. Exclusion criteria were preoperative CT scan showing a short ascending aorta (intrapericardial ascending aorta <6 cm), calcifications of ascending aorta at the site of cross clamping and at the site of the aortotomy, inadequacy for safe peripheral retrograde CPB (due to occlusive or aneurysmal peripheral vessels), redo surgery, reconstructive surgery of the aortic annulus, and requirement of associated surgery of the ascending aorta . Early postoperative life quality assessments (SF-12, I.A.D.L. scale) are included in the protocol. Six centers have formally accepted to participate in the study and data are being processed since January 2018. A target of 200 patients is planned to be included in the study. This is a first initiative step before designing a study comparing this patient subset to similar patients who have undergone transcatheter aortic valve implantation. Early results of over 60 patients will be included and presented. Figure PC39-1. Second-space no-rib-spreading right anterior minithoracotomy (left) and video-assisted aortic valve debridement (right). Robotic-assisted mitral valve surgery has been validated and practically used. Meanwhile, robotic-assisted aortic valve aortic valve surgery is still challenging and debatable in methodology. We retrospectively collected data and assessed feasibility on 2 patients, who underwent robotic-assisted aortic valve replacement (AVR) in our institution. Two patients with severe aortic valve stenosis, mean age of 75 (73 and 78), underwent robotic-assisted AVR. Peripheral cannulation was achieved via the right femoral artery and vein. A 12-mm endoscopic port was inserted into right 2nd intercostal space. Two separate 7-mm ports were inserted in the 1st and 3rd intercostal space. The endoscopic ports were adapted to the da Vinci robotic system (Intuitive Surgical, Sunnyvale, CA, USA). Using robotic assistance, the pericardium was opened and anchored to the skin from outside to expose the aorta. A small working incision was made in the same intercostal space as the camera port. After full heparinization, cardiopulmonary bypass was initiated.A vent cannula was placed through the right superior pulmonary vein and a cardioplegia cannula in the ascending aorta. The aorta was separated from the pulmonary artery and then cross-clamped with the transthoracic aortic cross-clamp placed through the 2nd intercostal space in the anterior axillary line. After cardioplegic arrest, the aortic valve was exposed through a clam shell aortotomy. Valvectomy along with decalcification of the annulus of the aortic valve was performed. Three guiding sutures of 3-0 prolene were inserted in the nadirs of each aortic sinus. The Perceval S valve (Liva Nova, Milan, Italy) was parachuted down using 3 guiding sutures and deployed. After confirming valve position, the aortotomy was closed. One patient developed atrial fibrillation postoperatively. Otherwise postoperative convalescence was uncomplicated. Robotic assistance as an addition to minimally invasive aortic valve procedure enabled excellent exposure of the aortic valve and improved manipulation and suturing of the aortic annulus and aorta. There needs to be improvement of instrumentation for valve debridement and removal of calcium from the annulus. In addition, the sutureless or rapid deployment valve technology further contributes to the feasibility and the efficacy of this procedure. Minimally invasive approaches to mitral valve surgery have prevailed recently, but have potential pitfalls because of the limited operative field. Clinical outcomes should not be compromised at the cost of a smaller incision. To ensure the patient’s safety, access to a good operative field is mandatory, but unexpectedly poor operative fields are sometimes encountered. We developed a new device, so called “Loop Retractor,” for better access to an operative field in the setting of minimally invasive mitral valve surgery. Loop retractor we developed makes the limited operative field in itself larger, by letting a stainless steel wire in the shape of loop enlarged, when mitral annuloplasty is performed. After placing the strings for annuloplasty, loop retractor is reset inside the strings and it makes the operative field larger, by letting a loop enlarged. Then, valve plasty such as resection and suture and neochord reconstruction makes the manipulation of mitral surgery easier. A new device, namely “Loop Retractor,” makes the limited operative field larger, and makes manipulation of mitral surgery easier. Loop retractor could help surgeons when they perform minimally invasive mitral surgery. Figure PC41-1. The aging of the population in western countries has determined the increase of fragile complex patients due to multiple comorbidities. Among these, a significant number of octogenarians with mitral disease are not referred to surgical treatment because of the high operative risk. We performed a retrospective analysis of our 12-year experience in mitral valve surgery. One thousand five hundred sixty patients underwent mitral valve surgery from January 2006 to March 2018. Patients under 80 years were excluded (1,432), resulting in a reference population of 128 octogenarians: 96 patients (75%) were operated with minimally invasive technique (MIMVS) and 32 (25%) with standard technique (sternotomy). The preoperative characteristics of MIMVS compared to sternotomy are comparable in most variables, and they differ only in pulmonary hypertension (47.1 ± 16.7 vs. 56.4 ± 15.5, p < 0.01, respectively). There were no differences in intraoperative data: comparable cardiopulmonary bypass (128.5 ± 39.7 vs. 122.4 ± 50.7 minutes, p > 0.05) and aortic cross-clamping time (85.5 ± 28.5 vs. 84.6 ± 31.6 minutes, p > 0.05). Mitral repair rate was higher in the MIMVS group (36.5% vs. 25.0%, p > 0.05). The only exception was a more frequent tricuspid-associated procedure in the sternotomy group (50% vs. 3.5%). MIMVS outcomes compared to sternotomy showed reduction of ventilation time (37.2 ± 104.2 vs. 52.8 ± 84.9 hours, p < 0.0001), intensive care unit stay (4.0 ± 8.6 vs. 4.4 ± 5.4 days, p < 0.0279), transfusions (3.6 ± 5.1 vs. 4.3 ± 2.8, p < 0.0158), thoracentesis (2.1% vs. 15.6%, p < 0.0107), creatinine values (0.99 ± 0.46 vs. 1.23 ± 0.63 mg/dl, p < 0.0334), total complications (0.5 ± 0.9 vs. 1.3 ± 1.1, p < 0.0001), and 30-day mortality (3.1% vs. 15.6%, p < 0.0232). A propensity score (area under the curve = 0.82) was used to identify 27 patient pairs. The matched comparison confirmed a trend of advantage for MIMVS: less prolonged ventilation (7.4% vs. 15.4%), reintubation (7.4% vs. 11.1%), tracheostomy (3.7% vs. 7.4%), intensive care unit stay (2.9 ± 3.4 vs. 3.4 ± 5.0 days), patients transfused (40.7% vs. 55.6%), re-exploration for bleeding (3.7% vs. 11.1%), neurological events (7.4% vs. 11.1%), pacemaker implantation (0.0% vs. 7.4%), and hospital stay (10.5 ± 4.2 vs. 11.6 ± 7.3 days), respectively. Significant advantage for MIMVS remained in ventilation time (22.5 ± 29.5 vs. 40.3 ± 77.5 hours, p = 0.0105) and total complications (0.6 ± 0.9 vs. 1.1 ± 0.9, p = 0.01539). In octogenarians MIMVS is feasible, reduces hospitalization, complications, and postoperative morbidity and allows early postoperative mobilization as well as improved quality of life. Thoracoscopy-assisted minimally invasive mitral valve repair (MICS-MVR) through a small right thoracotomy is a novel technique for mitral valve surgery and is increasingly adopted worldwide. This study aims to identify areas of improvement by describing characteristics of MA’s tri-port chest thoracoscopic cardiac surgery and mid-term outcomes of a series of MICS-MVR. This surgical breakthrough is known as the MA technique (MAT) in clinical literature. MAT was first pioneered by the author and his research team in 2009. It is a form of totally thoracoscopic heart surgery conducted through three ports on the right chest wall and belongs to the field of microsurgery. The associated procedure is simple and effective, leading to minimal surgical trauma. As of October 2018, MAT has witnessed 2,166 cases of successful application. Among them, 762 cases treated for rheumatic mitral valve disease involved patients aged 32–81 years and weighed from 43 to 106. Moreover, 697 treated cases consisted of mitral valve replacement and 55 cases for mitral valvuloplasty. An additional 36 control patients were recruited to undergo open-chest MVR. Patient information is collected for further statistical analysis. The data processed include but are not limited to preoperative cardiac information, operation time, cardiopulmonary bypass (CPB) time, cardiac arrest time, intensive caer unit (ICU) stay duration, ventilator-support time, hospitalization period, postoperative drainage volume, blood transfusion rate, incidence of morbidity, rate of mortality, and postsurgery assessment. Postsurgery information points to a 14.3% blood transfusion rate and a postoperative ventilator-support time ranging from 3.1 to 29.4 hours (with a mean and deviation of 5.1 ± 0.8 hours). Similarly, pleural fluid drainage ranged between 45 and 650 ml (95 ± 26 ml). The research team tabulated a 19-hour average ICU stay length with a range of 3–56 hours. An average 6.1-day postsurgery hospitalization time that ranged between 4 and 14 days for all 762 treated cases of rheumatic mitral valve disease was also computed. It is pertinent to note that there were 2 cases of death, 2 cases that required conventional open surgery, 9 cases of pulmonary infection postoperative, and 12 cases of secondary hemostasis. The team tracked 750 cases for 1–94 months in a subsequent follow-up. This group of patients had 3 cases of death in post-hospital discharge, and 2 cases of death resulting from cardiac causes. Compared to the control group, MAT significantly reduces the time associated with surgical operation, CPB, cardioplegia, ICU length of stay, ventilator support, and hospitalization. Additionally, MAT has smaller odds of complication and postoperative drainage while lowering the rates of blood transfusion and use of pain medication. Through repeated surgical amendments, MAT has evolved to deliver clinical excellence and is more advantageous than the conventional surgery. It overcomes the drawbacks of small-incision-based cardiac surgery in terms of field of vision, procedural challenges, surgical trauma, and postsurgical pain in tandem to circumventing the shortcomings of robotically assisted heart surgery. To report early and late clinical results comparing right minithoracotomy (RMT) versus full sternotomy (FS) mitral valve surgery (MVS). Five hundred seventy-four consecutive patients who underwent MVS were prospectively nonrandomized reviewed during January 2002–October 2018. There were 241 in FS group and 241 in RMT group by propensity matching. Baseline characteristics were compared. Early and late clinical outcomes of 30-day mortality, reoperation for bleeding, stroke, prolonged ventilation, renal failure, permanent pacemaker, and echocardiographic hemodynamic performance were assessed and compared between 2 groups. Similar results were found between RMT and FS MVS groups including age 58.8 ± 13.6, 57.2 ± 14.2, p = 0.2, new atrial fibrillation 5 (2%), 4 (1.7%), p = 1.0, and reoperation for bleeding 2 (0.8%), 1 (0.3%), p = 0.9. There were more degenerative valve pathology (79%, 45.6%, p < 0.001), less aortic cross-clamp time (107 ± 37.3, 115.4 ± 36.4, p = 0.017), less cardiopulmonary bypass time (157.6 ± 51.2, 171.3 ± 53.4, p = 0.005), less bleeding, and blood transfusion requirement in the RMT group. Early clinical results of 30-day mortality, stroke, renal failure, new pacemaker, and hemodynamic performance at 1 month, 3–6 months, and 1 year were comparable in both groups. Mean follow-up (year) was 5.2 + 2.5 (RMT) and 10.2 + 4.0 (FS). Survival probability and freedom from major cardiac and cerebrovascular events at 10 years in the RMT and FS groups were 94.05%, 95.44% and 99.5%, 90.46%, p < 0.001, respectively. RMT approach for MVS is associated with cosmetic satisfaction, less bleeding, blood transfusion requirement, similar effective hemodynamic performance, and comparable early and late clinical results to FS approach. To investigate the efficiency and safety of totally endoscopic tricuspid ring annuloplasty technique on beating hearts in combination with atrial septal defect (ASD) repair. Twenty-four patients (39–71 years, mean 52.2 ± 12.3) underwent ASD closure and tricuspid ring annuloplasty on beating hearts by a totally endoscopic approach. All of them had moderate-to-severe tricuspid valve regurgitation (TVR) with mean pulmonary artery pressure (PAP) was 61.8 ± 10.89 mmHg. Cardiopulmonary bypass was achieved peripherally. Three 5-mm trocars and one 12-mm trocar were used; only the superior vena cava is snared, filling the pleural and pericardial cavities with CO2. Tricuspid ring placement was successful in all cases. No extension of the incision was needed. Mean bypass time was 90.2 ± 12.04 minutes. After surgery, there were 15 cases with nontrivial TVR and 9 cases with mild TVR. Postoperative mean PAP was 28.4 ± 12.19 mmHg. No arrhythmia or atrioventricular block was recorded. Tricuspid ring annuloplasty in nonrobotic totally endoscopic ASD closure on beating hearts is a safe and an efficient technique. Figure PC45-1. Advance technological improvement has facilitated the implementation of minimally invasive approaches in cardiac surgery even for redo interventions. Redo heart valve surgeries via sternotomy are associated with substantial morbidity and mortality. This study evaluated the minimally invasive technique for heart valves implantation in patients undergoing redo cardiac surgery. Three hundred eighty-five patients underwent aortic, mitral, and/or tricuspid valve repair or replacement via a right minithoracotomy between June 2013 and December 2018 in our center, and 45 patients underwent redo valve surgery using a minimally invasive approach. Previous cardiac surgeries included 14 patients with aortic and mitral valve replacement, 19 patients with coronary artery bypass grafting, and 12 patients with mitral valve repair or replacement. In all cases, femoro-femoral cannulation was performed. Three-dimensional video-assisted access technique was applied in all patients concomitantly. Most of the operations were performed using normothermia cardiopulmonary arrest except in the cases with isolated tricuspid valve repair or replacement and isolated mitral valve repair (n = 5) in whom the aortic valve competence was normal. In addition, continuous carbon dioxide is used, and adequate de-airing is monitored by transesophageal echocardiography. In all cases, a sternotomy was avoided. The mitral valve was replaced in 20 patients and repaired in 19. The outcomes of patients (in-hospital mortality about 1.55%) are encouraging and intraoperative times are highly competitive with published data on the standard full sternotomy. Time of surgery and cross-clamp time were compared with the overall series (168 ± 73 [redo] vs. 168 ± 58 minutes and 52 ± 21 [redo] vs. 58 ± 25 minutes). Two patients had transient hemiplegia due to air embolism. All other patients had uneventful outcomes and normal valve function at first-year follow-up. Redo valve surgery can be performed safely using a minimally invasive approach in patients with a previous sternotomy. The right anterior or lateral minithoracotomy offers excellent exposure. It minimizes the need for cardiac dissection, and, thus, the risk for injury. Avoiding a resternotomy increases patient comfort of redo mitral valve surgery. Mitral valve surgery in patients who have undergone coronary artery bypass grafting (CABG) using bilateral internal mammary artery (BIMA) is of particular risk when performed through redo sternotomy. The outcome of minimally invasive mitral valve surgery (MIMVS) via a right anterolateral minithoracotomy (5–7 cm) that can also be performed without aortic clamping has not yet been evaluated in these patients. From 534 patients undergoing MIMVS between January 2012 and April 2018 at our institution, 10 patients (median age 72, 8 male) required MIMVS at 99 months (33–179) postoperatively. Nine of the 10 patients underwent the procedure under hypothermic ventricular fibrillation without aortic clamping. The preoperative, intraoperative, and postoperative data were retrospectively collected and analyzed. Preoperative left ventricular ejection fraction (LV-EF) was 44 (30%–55%) and EuroScore II was 25.0% (6.7–33.0). Mitral valve replacement with biological prosthesis was performed in 8 (80%) and reconstruction in 2 (20%) patients. Four patients (40%) required concomitant tricuspid valve repair. There was no conversion to sternotomy, no intraoperative death, no postoperative neurological deficit, no bypass damage, and no myocardial infarction. Reoperation for bleeding was required in 2 patients, whereas cardiac resuscitation was required in 1 patient. Reintubation was necessary in 3 (30%) patients and temporary hemodialysis in 4 (40%) patients all suffering from sepsis. Cardiac arrhythmias were documented in 6 patients, from which one required pacemaker implantation. The median intensive care unit stay was 5 days (3–10), whereas hospital stay was 9 days (7–19). Mortality at discharge was 20% and was associated with resuscitation and sepsis. All discharged patients (80%) survived the follow-up period of 21 months (9–29) without complications. MIMVS can be performed safely after BIMA CABG also in elderly patients with reduced LV-EF. The low mortality was not related to the operative characteristics and postoperative cardiac function, but rather to advanced age, postoperative need for mechanical ventilation and dialysis, development of sepsis, and multiorgan failure. Surgical robotics allows incision size to be dramatically reduced with expedited postoperative recovery. Percutaneous approaches to cannulation have reduced the morbidity of transcatheter procedures. We report our early experience performing totally endoscopic robotic cardiac surgery with percutaneous access. From July 2018 through December 2018, 29 consecutive patients underwent totally endoscopic robotic cardiac surgery with percutaneous peripheral cannulation. The mean age was 62.3 years (34–80), 13 male, 16 female, and mean body mass index 29.8 (19.6–58.1). Robotic procedures included mitral valve repair (17), mitral valve replacement (5), atrial septal defect closure (3), septal myectomy (2), and atrial mass resection (2). Thoracic access was composed of four 8-mm robotic ports. Additionally, there was one 12-mm working port for the bedside assistant, except mitral valve replacement that requires a 35-mm port. All percutaneous cannulation were achieved with surface ultrasound, transesophageal echocardiography, and fluoroscopic guidance. Percutaneous pulmonary artery vent and retrograde cardioplegia catheters are placed by anesthesia. The surgeon places a common femoral multistage venous canula, common femoral arterial canula, and internal jugular venous canula for superior vena cava drainage. A preclose technique is used to facilitate decannulation. The aorta was occluded using an endoaortic balloon. Lower-extremity perfusion is monitored continuously with tissue and pulse oximetry. At the conclusion of the case, vascular Doppler ultrasound is used to confirm arterial flow. The mean hospital stay was 4.7 days (1–16). Aortic clamp and cardiopulmonary bypass times were 75.9 (29–108) and 119.1 (67–148) minutes, respectively. No patient was converted to thoracotomy or sternotomy. There were no hospital or follow-up mortalities. There was one patient with acute limb ischemia following deployment of a percutaneous vascular closure device related to a posterior plaque. This was immediately diagnosed, and an endarterectomy was performed with good result. All patients have reported no pain at the site of cannulation and there have been no lymphoceles or other complications related to cannulation. Our experience with endoscopic robotic cardiac surgery with percutaneous cannulation suggests that this technique is both feasible and safe. To our knowledge these cases represent the smallest-incision open heart surgery currently being performed in the world today. Table PC48-1. Robotic Endoscopic Cardiac Surgery with Percutaneous Cannulation AV: atrioventricular; BMI: body mass index; VATS: video-assisted thoracoscopic surgery. Thymectomy is the most important treatment for anterior mediastinal mass and myasthenia gravis (MG). Until now, different surgical approaches have been described to perform thymectomy, from median sternotomy to robotic thymectomy. But there is no consensus on the best approach of thymectomy. Depending on the approach to perform thymectomy, the advantages and disadvantages are different. Currently, the lateral intercostal approach in video-assisted thoracoscopic surgery thymectomy (VATS thymectomy) is the most frequently performed surgical approach for thymectomy. But this approach has difficulty to identify the contralateral phrenic nerve and intercostal nerve impairment. Recently, to overcome the shortcomings of VATS thymectomy, subxiphoid single-port thymectomy (SPT) was introduced. We have performed modified subxiphoid SPT using our own manufacturing sternal retractor without carbon dioxide insufflation under one-lung ventilation. We report the initial operative results of modified subxiphoid SPT. Subjects of this study were patients who underwent thymectomy or extended thymectomy at Inje University Haeundae Paik Hospital between July 2016 and November 2018. We reviewed the medical records of these patients retrospectively. Indication of thymectomy is anterior mediastinal mass without tumor invasion. In our department, we performed thymectomy for anterior mediastinal mass in the absence of MG. And extended thymectomy, which involves the removal of all adipose tissues anterior to the phrenic nerve, was performed for MG. Subxiphoid uniportal thoracoscopic thymectomy was attempted first in July 2016. From this time, thymectomy for anterior mediastinal mass or extended thymectomy for MG was preformed via SPT with sternal retraction. All surgical procedures were performed by a single surgeon. Twenty nine patients who underwent thymectomy or extended thymectomy were enrolled. Information of patient demographics, and intraoperative and postoperative data were collected and retrospectively evaluated. The patient’s demographics are presented in Table PC49-1. The results of operative outcome of subxiphoid SPT are presented in Tables PC49-2 and PC49-3. Table PC49-1. Patients’ Demographics Table PC49-1. Patients’ Demographics Table PC49-2. Operative Outcomes Table PC49-2. Operative Outcomes Table PC49-3. Pathologic Diagnosis Table PC49-3. Pathologic Diagnosis The benefit of subxipohid approach with sternal retraction is that it makes it easier to identify the contralateral phrenic nerve. Also, our procedure has 3 advantages when compared with carbon dioxide insufflation subxiphoid SPT. First, because we do not insufflate carbon dioxide, there is no need to worry about hypotension. Second, we do not use air tight trocar, so we use more instruments and have more flexibility in them. Finally, sternum retraction provides more optimal space for the surgery. SPT through the subxiphoidal incision using sternal retractor under one-lung ventilation without carbon dioxide insufflation was feasible. Pericardial effusion, besides being a complication of cardiac surgery, may be caused by renal impairment, infections, neoplasms, or autoimmune diseases. As it is not simple to diagnose its etiology, pericardial drainage is often necessary for both therapeutic and diagnostic purposes. The target of this study is to demonstrate the safety, simplicity, and usefulness of subxiphoid drainage. Between September 1, 2015 and September 30, 2018, 12 patients underwent subxiphoid drainage, 7 patients had a failed pericardiocentesis, 2 patients had late pericardial effusion after cardiac surgery, and 10 had pericardial effusion of an unknown origin. Six patients underwent emergency drainage. All procedures were performed in awake patient without intubation. After Xylocaine local anesthesia, a 3-cm incision was performed above the xyphoid process. Once the pericardium was opened, liquid samples were sent for chemical-physical, cytological, and bacteriological examination. Also, it was always possible to send a fragment of pericardium for histological examination. A small drainage was placed and wound closed. No patient died due to the procedure, and no patient required intubation or intensive care stay. All patients were discharged 48 hours after the procedure. Excluding cardiac surgery patients, the etiology was uremic in 2 patients, infectious/viral in 2, malignant in 3, and idiopathic in the rest of the cases. No patient had a recurrence of pericardial effusion after 30 days. Subxiphoid pericardial drainage is a simple and a safe procedure, even in patients undergoing cardiac surgery in the past, where pericardiocentesis could be difficult and dangerous. It does not require intubation of the patient and above all no need for long hospital stay. It allows to send pericardial portions useful in the differential diagnosis of tumor pathology. Thoracic surgery has seen a significant increase in the use of robotic-assisted thoracoscopic surgery (RATS) with an aim to replace current video-assisted thoracoscopic surgery (VATS). Thymectomy is a common procedure used in the early stages of RATS training to introduce surgeons to the robotic method. The aim of this project is to evaluate the early learning curve of RATS compared with VATS for thymectomy and its impact on length of stay. Data were prospectively collected between 2015 and 2018 for all VATS and RATS thymectomy cases completed in a tertiary thoracic center. Baseline patient characteristics, operating times, and length of stay were recorded in the chronological order of date of surgery. All cases that were converted to sternotomy were discounted from analysis. Median (interquartile range) operating times were calculated and linear regression analysis completed to assess correlation between operating times and days from first procedure for RATS cases, initial VATS cases, VATS cases performed by the robotic surgeons, and all VATS cases performed in the center. Mann–Whitney U test was used to compare the length of stay between RATS and VATS. p < 0.05 was considered significant. There was a total of 41 thymectomies performed comprising of 31 VATS and 10 RATS procedures. The median operating time for all VATS thymectomies (n = 31) was 137 (56) minutes (r2 = −0.1004, p = 0.0825). For the surgeons now performing RATS thymectomy, the median VATS operating time (n = 21) was 133 minutes (55.5) (r2 = −0.111, p = 0.1399) with the median time for their first 10 VATS thymectomies 147 minutes (63.8) (r2 = −0.2855, p = 0.1116). RATS thymectomy operation times had a median of 136.5 minutes (47.8) (r2 = −0.2224, p = 0.1688) and have crossed the median operating time for all VATS thymectomies performed in the center. Mean length of stay was 2 days in RATS thymectomy and 4 days in VATS thymectomy (p = 0.006). Figure PC51-1. RATS operations with median VATS time X = Time from first operation (days), Y = Operation time (min) RATS: Robot-assisted thoracoscopic surgery, VATS: Video-assisted thoracoscopic surgery. Transfer of the surgical skills of thymectomy from video-assisted to robotic-assisted surgery helps surgeons achieve similar initial learning curves and may explain the reduced operating times in early RATS thymectomy. The benefit in reduction of length of stay supports the adoption of RATS in other aspiring thoracic centers. Hydatid cyst caused by Echinococcus granulosus is endemic in Asia. Pulmonary hydatid does not have a uniform treatment recommendation. This case series presents the thoracoscopic management of hydatid disease from India. Retrospective multicentric case series of patients treated between 2003 and 2018 at three multispeciality centers was included in this study. Twenty-one patients with an average follow-up of 17 months were included. Thoracoscopic surgery was performed in all 21 patients with a mean duration of hospital stay of 5 days and mean age 33 years, and there was no recurrence noted at 6 months follow-up. Thoracoscopic surgery helps in faster recovery early back to work and there were no added complications and hence needs to be offered in all patients with hydatid cyst. Pulmonary metastasectomy is a commonly performed operation and tends to further increase as part of a concept for personalized treatment in advanced stages of cancer. Various surgical tools have been utilized to improve the resectability of pulmonary metastases while reducing the rate of complications: from electrosurgical instruments and mechanical staplers to Nd:YAG laser. More recently, pure argon plasma has provided an electrically neutral energy source for cutting and coagulating tissue with minimal depth of necrosis. These characteristics make argon plasma energy an appealing candidate for pulmonary metastasectomy, where the goal is complete excision of the lesion with simultaneous aerostasis, hemostasis, and preservation of lung parenchyma. In this study, we assess the safety and efficacy of thoracoscopic pulmonary metastasectomy with argon plasma energy and we compare its clinical results with those observed by using more conventional surgical technologies. During a two-month period, 5 patients (3 males and 2 females) aged between 67 and 85 years (mean age of 77 years) underwent uniportal video-assisted thoracoscopic surgery for pulmonary metastasectomy with the use of argon plasma energy. All patients had a medical history of colorectal carcinoma and presented with a solitary, less than 3 cm in maximal diameter, peripherally located lung lesion with radiological features suspicious for metastasis. In all cases, histopathological analysis of the lesion confirmed colorectal metastasis that was completely excised. The mean operative time was 22 minutes (range, 18–25). All surgeries were performed without complications, including bleeding and air leakage, thus allowing removal of the intercostal chest drain on the following day. All patients were discharged on the first postoperative day and were followed up for a mean period of 6 months (range, 4–8 months), during which no complications occurred. The use of argon plasma energy for thoracoscopic excision of pulmonary metastases appears to be simple, safe, and efficacious. When compared to more conventional surgical techniques, argon plasma energy represents a valid alternative method for pulmonary metastasectomy. Intercostal thoracic surgical incisions are painful and in the postoperative period following open or thoracoscopic surgery patients typically require significant amounts of opioids to provide adequate perioperative analgesia. However, the use of opioids is commonly associated with adverse effects such as opioid-induced hyperalgesia, sedation, nausea and vomiting, and postoperative ileus. It is recognized that these complications can delay patient mobilization and hospital discharge. We have successfully piloted the use of opioid-free anesthesia (OFA) in patients undergoing lung cancer resection at our center. All data were recorded prospectively. The anesthetic technique comprised induction of anesthesia with intravenous lidocaine, propofol, and nondepolarizing muscle relaxant; locoregional analgesia (i.e. serratus anterior plane block or paravertebral block) and pre-incision paracetamol, parecoxib, and magnesium sulfate as routine. Clonidine and phrenic nerve blocks were also used in selected patients. All patients received postoperative patient-controlled analgesia with morphine. Continuous data are presented as mean ± standard deviation; nonparametric data are expressed as median (interquartile range [IQR]). During the pilot, 37 patients were included in the study: 23 male and 14 female. The mean age was 67.7 ± 10.3 years. The mean body mass index was 28.3 ± 5.7 kg/m2with median American Society of Anesthesiologists’ status 3 (range 2–4). The mean percentage predicted forced expiratory volume in 1 second was 88.0% ± 23.1%. The mean 6-minute walk test distance was 367 ± 108 m. The surgeries included 32 lobectomies and 5 anatomical segmentectomies; 31 procedures were performed thoracoscopically (28 uniportal, 2 subxiphoid, and 1 multiportal) and 6 were performed by thoracotomy. The mean duration of surgery was 189 ± 58 minutes. The mean length of stay in the postanesthetic recovery area was 114 ± 37 minutes. The mean opioid consumption of the patients within the first 24 hours was 15.5 ± 20.7mg. The median hospital length of stay was 3 days (IQR 2–4). We have demonstrated that OFA is feasible and safe in patients undergoing thoracic surgery and it should be considered as part of the enhanced recovery programmes, to minimize the complications associated with the perioperative use of opioids. The introduction of the robotic system in thoracic surgery has revolutionized the treatment of pulmonary and mediastinal pathologies. Over the years, different technological upgrades have allowed the surgeons to change the technique. The aim of this study was to illustrate the impact of three upgrades in robotic thoracic surgery: the use of robotic staplers for lung resections, the green indocyanine infusion associated with intraoperative infrared vision for identification of pulmonary nodules and phrenic nerve during thymectomies, and the technical improvements between third and fourth generations of robotic system. We retrospectively analyzed 20 patients who underwent anatomic pulmonary resection for non-small-cell lung cancer (NSCLC) from January 2015 to January 2016. Patients were divided into 2 groups: group I: 10 patients, resections performed with robotic staplers and group II: 10 patients, resections performed with endoscopic staplers. We evaluated the effectiveness in terms of postoperative complications and postoperative pain. We evaluated 20 patients in which the indocyanine green infusion was used for the visualization of suspicious nodules for NSCLC (5 patients) and visualization of the phrenic nerve during thymectomies (15 patients). We retrospectively evaluated 52 patients who underwent robotic thymectomy (group I: 23 patients treated using the 3rd robotic generation, group II 29 patients treated with the 4th generation). We evaluated effectiveness in terms of postoperative pain and analgesic request. Figure PC55-1. No postoperative complication in both groups. Lower mean numerical rating score (NRS) and analgesic request in group I. The use of indocyanine green has proved to be useful in the identification of invisible pulmonary nodules and in the execution of thymectomy in case of thymomas adjacent to the phrenic nerve. We found a statistically significant difference in the mean value of the NRS 24 hours after surgery (p < 0.05). Group I 4.07 (standard deviation [SD] 2.51), group II 1.72 (SD 1.15), and a statistically significant difference in the administration of analgesics. Group I 2.62 administrations (SD 0.94), group II 1.52 administrations (SD 1.12) 1 day after surgery. The evolution of technology has improved the execution of robotic surgical procedures with a positive impact on postoperative outcomes. Video-assisted thoracoscopic surgery (VATS). We present a case of successful removal of an 8.5-cm noncompliant mass with a broad attachment to the parietal pleura. We describe a complex clinical case report of a patient who underwent VATS mass resection. We describe a 34-year-old male who presented to University Medical Center after an acute onset of dyspnea. A chest radiograph and subsequent computed tomograph chest revealed a large posterior mediastinal mass at 8.0 × 8.0 × 8.5 cm. Mass excision was scheduled by VATS vs. thoracotomy. The attachment to the parietal pleura was very broad with an array of venous and arterial vasculature. A 30° camera scope was able to maneuver tight imaging windows. Some bleeding was encountered that was easily controlled with sponge stick and pressure. The posterior mediastinal mass was successfully removed by VATS resection. VATS as a minimally invasive surgical resection for a large posterior mediastinal mass is not well described. Tumor greater than 4 cm is a soft contraindication to VATS removal. The benefits of VATS vs. thoracotomy have been thoroughly explored. Knowing when to convert given bleeding, loss of visualization, and inability to perform with appropriate dexterity are all reasonable concerns leading to thoracotomy conversion. An algorithm must also exist for the more senior surgeon contemplating when one should and could remain in VATS. Several types of annuloplasty rings and bands have been used in mitral valve repair (MVP) with different concepts, but their actual effects on left ventricular hemodynamics especially on mitral inflow and aortic outflow have not been fully revealed. We performed vortex flow evaluation with four-dimensional (4D) flow magnetic resonance imaging (MRI) in patients after MVP. Twenty-one normal controls, 7 patients with CG future band (CG), 5 with Physio II ring (PHY), and 1 with Tailor band (TA) with different sizes were examined in 4D flow MRI. Influences of annuloplasty procedure types on diastolic intraventricular vortex flow patterns and systolic aortic outflow patterns were examined in addition to flow energy loss (EL) in 1 cardiac cycle. The band sizes of CG were 28 mm in 1 patient, 30 mm in 1, 32 mm in 1, 34 mm in 2, and 36 mm in 2, and the ring sizes of PHY used were 28 mm in 1 patient, 30 mm in 1, 32 mm in 1, 34 mm in 1, and 36 mm in 2, and the ring size of TA used was 33 mm. Diastolic intraventricular flow after MVP made larger vortices beneath anterior and posterior leaflets compared with those in normal controls. Anterior vortices after MVP were consisted of 2 strands. Relationship between EL and the transmitral mean pressure gradient during diastole was significant (r = 0.63, p = 0.04). In systole, some patients with smaller rings or bands compared with patient’s body size had disturbed outflow due to vortex flow inside left ventricle (LV), resulting in high EL. PHY restricted aortic annulus systolic motion, and then it caused slight EL elevation with EL distribution pattern changed. Mean arterial pressure patients had larger left ventricular vortex in diastole regardless of the repair type than the healthy volunteer. In systole, small-size annular ring or band caused narrowed LV outflow pattern. The effect of vortex flow pattern change on long-term ventricular function after the MVP is to be studied. Aortic valve reconstruction with three same-sized autologous pericardial leaflets (AVLR) has been performed for patients with narrow aortic roots or contraindication for valve prostheses. Since this procedure requires precise information of the aortic root including configuration of Valsalva sinus, we assessed physiologic-anatomical condition of the aortic root by virtual reality (VR) image in order to accomplish this technique with a reproducible fashion. VR imaging; axial images using enhanced electrocardiogram-triggered cardiac computed tomography with a slice thickness of 0.625 mm were obtained during mid-to-end diastole. Subtracted volume rendering data of the aortic root were converted to a 3D workstation. Basic surgical technique: (1) three same-sized leaflets from autologous pericardium were prepared by original templates referred by STJ diameter; (2) new commissures and nadirs were confirmed based on VR image in cases of unbalanced aortic root, like type 0 bicuspid valve; (3) three leaflets were sutured on cusp-suture-line; (4) commissure coaptation stitches were placed between each leaflet to prevent from minor leakage and coronary orifices obstruction. Twenty-four of 82 AVLR were evaluated by VR. In 15cases, the Valsalva sinus was unbalanced, which required neo-commissure setting and adjustment of deviated nadir. Postoperative echocardiography revealed nice opening of new leaflet with no aortic regurgitation, although we had one case without 3D analysis who had taken down to AVR due to mild AR. A median follow-up period was 38 months, while we have no redo due to aortic valve failure. VR image analysis had notably provided valuable information for understanding of precise anatomy of the aortic root for AVLR. The validity of the high-frequency epicardial ultrasound (ECUS) in coronary artery bypass graft (CABG) has been described. However, the echo image is a partial cross section and is insufficient for the evaluation of three-dimensional (3D) structure. So, we intended for visualization and evaluation of CABG anastomosis by performing the real-time 3D construction of the ECUS images. ECUS we have chosen was VeriQ C (MEDISTIM, Oslo, Norway) to obtain the ultrasound images, and attached the electromagnetic position-tracking sensor (trakSTAR, Ascension Technology Corp., Sherburne, Vermont, USA) to ECUS probe. We implemented the function for integrating scanned ultrasound images with positional information and making them 3D in real time with the open-source 3D Slicer application (, SlicerIGT extension (, and PLUS toolkit ( We evaluated this system using CABG anastomosis model, which was made with the extracted pig heart. Harvested right coronary artery was anastomosed to left anterior descending artery, and normal saline was injected from the graft continuously. We scanned the CABG anastomosis model and created the 3D images ( Figure PC59-1(A) ). Figure PC59-1. Real-time three-dimensional imaging of coronary artery bypass graft anastomosis. (A) The system which built 3D image by the combination of ECUS and positional information sensor. (B) Scanned ECUS along LAD and provided a 3D image in real time. 3D: three-dimensional; ECUS: epicardial ultrasound; LAD: left anterior descending artery. Bypass graft and anastomosis evaluation using ECUS is valuable, because it describes the vessel lumen and anastomotic form more exactly. The anastomotic 3D construction was possible by volume rendering of the ultrasound images merging image stack on the z-axis with general-purpose software, but it needs too much editing time and it is unsuitable for intraoperative use. On the other hand, our method becomes able to edit the 3D image in a few minutes ( Figure PC59-1(B) ) and we can evaluate the anastomotic quality instantly. Furthermore, indications by 3D viewer or write output into 3D printer are possible. It is useful to view the anastomotic form from multidirectional angles. Real-time evaluation of the anastomotic form was enabled by 3D building of ECUS images by combining a position sensor. And it may be used for intraoperative graft evaluation in future by improving precision. To share this novel approach to a complex situation. A 68-year-old male had previously undergone an aortic valve replacement (AVR) in 2006. Subsequently he required a redo AVR and root replacement in 2016 but this was complicated by worsened mitral regurgitation, resulting in the need for a salvage mitral valve replacement via thoracotomy. Unfortunately this was further complicated by a trapped valve leaflet. He recovered well initially but represented with worsening heart failure. Due to the high risk of sternotomy, a transventricular cardioscopic release of the trapped mitral valve leaflet was undertaken. The procedure was successful and the patient was discharged home on day 12. This is a novel minimally invasive approach for high-risk patients with this rare complication. This technique is carried out using small incisions and negates the need for myocardial ischemia. We hope that by sharing it, others will consider this approach in the future. The aim of our study was to evaluate outcomes of a redo cardiac surgery using the endoscopic vaso-view system to facilitate sternal re-entry. Between May 2016 until June 2018, a total of 29 patients underwent redo cardiac surgery using the endoscopic vaso-view system introducing the blunt dissector through a small substernal incision, which facilitates blunt dissection of adhesions underneath the sternum making a space between the sternum and the heart under vision then followed by a sternotomy with an oscillating saw. All patients had preoperative computed tomography scan. A total of 29 patients were identified and the procedures performed were valvular surgery in 82% and coronary artery bypass grafting in 18% at King Fahad Armed Forces Hospital. Twenty-four percent were second redo and 76% were first redo. The patients’ characteristics were that the mean age was 55 ± 32 years, 65% were female, 45% were males, and mean left ventricular ejection fraction was 50% ± 30% with an average EuroSCORE II of 4.8 ± 1.6. Intraoperatively patients had femoral cannulation in 20.6%, central cannulation in 71%, and off pump in 3.4%, while the mean bypass time was 125 ± 20 minutes, cross-clamp time 111 ± 10 minutes, and 6.8% had right ventricular injury. Overall in-hospital mortality was 3.5%, mean intensive care unit stay 5 ± 3 days, and length of stay 16 ± 10 days. There was no reoperation for bleeding, mean blood loss in the first 24 hours was 474 ± 230 ml, number of blood products used intraoperatively was 1.4 ± 1 units and postoperatively 1.5 ± 1 units, stroke rate was 6.8%, atrial fibrillation 38%, and myocardial infarction 3.5%, there was no renal failure requiring dialysis, and 13.7% had prolonged ventilation. Redo cardiac surgery using the endoscopic vase view system to facilitate sternal re-entry showed that it is a safe and effective approach in our hands to clear adhesions under vision facilitating sternal re-entry. A comparative study will be our next step to validate our conclusion and encourage surgeons to adopt this approach. Minimally invasive coronary artery bypass surgery in selected patients can be performed safely and efficiently, with the markedly reduced postoperative length of stay when compared to conventional surgical revascularization. A left thoracotomy is preferred during minimally invasive direct coronary bypass (MIDCAB) for both left internal mammary artery (LIMA) harvesting and performing the anastomosis. However, LIMA harvesting is sometimes challenging via the thoracotomy, which makes some surgeons prefer not to harvest the proximal LIMA. We reported our experience in three-dimensional (3D) video-assisted LIMA harvesting in MIDCAB surgery. Twelve patients who underwent MIDCAB surgery had 3D video-assisted LIMA harvesting. In these patients, LIMA was harvested in the closed chest through 3 ports, 2 for surgical equipment and 1 for the 3D camera. Following the harvest, thoracotomy was performed for off-pump left anterior descending (LAD) artery-LIMA anastomosis. All the patients underwent 1 vessel MIDCAB surgery and LIMA was anastomosed to the LAD, following video-assisted harvesting. LIMA was harvested including the first branch and finished at the level of the distal bifurcation. Mean harvest duration was 31 + 9 minutes, and the mean operation time was 107 + 19 minutes. All the LIMA grafts harvested were anastomosed and there was no sternotomy conversion. Minimally invasive coronary procedures are becoming an important option for the treatment of coronary artery disease especially with the addition of 3D visions and robotic arms lately. Three-dimensional video assistance in closed chest allows LIMA harvesting in a safe and efficient way. In mitral valve (MV) surgery after previous sternotomy, right minithoracotomy and fibrillatory arrest (FA) offer the simplest approach with no need for mediastinal adhesiolysis. Despite this advantage, limited dissection and fibrillating heart sometimes yield limited exposure. A three-dimensional (3D) endoscope might facilitate to visualize and manipulate the MV, which enables totally endoscopic surgery. We present the earliest Korean experience of applying 3D endoscopic system in redo MV surgery with FA. Between May 2018 and November 2018, we performed aortic no-touch totally endoscopic redo MV surgery on 16 patients, 2nd time in 12 patients, 3rd time in 3 patients, and 4th time in 1 patient. All patients had undergone previous valve surgeries involving MVs only through sternotomy approach (EuroScore II 11.09% ± 7.91%). Previously implanted prosthetic aortic valves existed in 6 patients. All procedures were performed through 5–6 cm right minithoracotomy incision with 2 extra ports: a left atrial sump drain and a 10-mm scope trocar ( Figure PC63-1 ). Temporary pacing wires were implanted on the right ventricular anterior wall or right ventricular endocardium after right atriotomy, and left atrium was opened after inducing FA with a fibrillator. Figure PC63-1. Mean cardiopulmonary bypass time was 175.1 ± 33.4 minutes. No intraoperative events such as great vessel injury or lung laceration occurred. There were no perioperative mortality, postoperative bleeding reoperation, low cardiac output syndrome, pneumonia, or wound problem. One minor stroke (cerebellar embolic infarction) occurred in a patient with third-time redo MV replacement. Concomitant procedures including tricuspid valvuloplasty in 10 and maze procedure in 3 were performed. Our experience illustrates feasibility and safety of the 3D totally endoscopic right minithoracotomy approach under FA to treat mitral pathology without reoperative sternotomy risks. In the decision making of the surgical treatment of acute aortic dissection, the detection of the entry site is considered important. However, its accurate detection is sometimes difficult, because the computed tomography (CT) image is inevitable from the motion artifacts caused by the heartbeat. Electrocardiogram (ECG)-gated CT scanning can reduce such artifacts and may be useful in determining the entry site of aortic dissection. The accuracy of the entry-site detection was compared between ECG-gated CT images (sync images) and nongated CT images (async images). We extracted 20 CT images (9 sync and 11 async) from patents undergoing surgical repair of aortic dissection. Six physicians (2 cardiac surgeons, 2 radiologists, 2 medical interns), who were not informed the results of operations, participated in the study. The examinee reviewed the CT images to determine the entry site of aortic dissection, and the answers were verified with the operative findings. The examinee scored each CT image according to the easiness of entry site identification into a 5-point scale. The entry site was correctly determined in 22.7% for async images. The correction rate was improved to 70.4% for sync images (p < 0.001). The difference was remarkable in medical interns or cardiac surgeons (async: 9.1% vs. sync: 63.9%), compared with the radiologists (50.0% vs. 83.3%). The average readability score was higher in sync images (async: 2.8 vs. sync: 4.5). The accurate detection of the entry site based on the conventional CT images may be difficult for nonprofessionals. ECG-gated CT scanning is considered useful to determine the entry site in aortic dissection. The CorCinch functional mitral regurgitation (fMR) study is a multicenter, nonrandomized, prospective early feasibility study. The objective of the study was to evaluate the safety and performance of the AccuCinch® Ventricular Repair System and assess the indices of heart failure and functional mitral regurgitation in symptomatic adult patients with mitral regurgitation and left ventricular remodeling due to dilated cardiomyopathy (ischemic or nonischemic etiology), who are of high operative risk. The AccuCinch® employs a catheter-based delivery system retrograde via the femoral artery to deliver a series of anchors into the subvalvular myocardium, using a flexible cinching cable to thereby directly reduce the basal left ventricular diameter. Procedures were performed under general anesthesia using fluoroscopy and transesophageal echocardiography guidance. Single-center data from Nebraska Heart Hospital were collected on all patients for safety, echocardiographic, and clinical outcomes as well as a subset of patients receiving a later, modified implantation technique. Longer-term follow-up data will also be presented as available. All 6 patients underwent AccuCinch implantation procedures and there were no 30-day adverse events (or serious adverse events) from this initial series. Echocardiographic follow-up was performed on all over the course of 6 months. Of the 4 patients receiving the latest implantation technique, average ejection fraction improved from 33% to 46%, left ventricular end-systolic volume decreased from 104 to 67 ml, and regurgitant volume decreased from 62 to 31 ml. Average 6-minute walk test for these patients increased from 182 to 218, while their average overall summary KCCQ quality-of-life scores improved by 14 points, from 46 to 60 points. These findings provide early feasibility data supporting the concept that a percutaneously delivered, basal left ventricular implant that cinches the myocardial wall below the mitral annulus has the potential to improve left ventricular function and reduce the severity of fMR. Surgical management of residual pulmonary regurgitation (PR) after initial repair of some congenital heart defects is truly challenging. Transcatheter pulmonary valve replacement (TPVR) is a new, less-invasive alternative to surgical valve replacement. We report the first-in-man implantation using a novel designed TPV device for patients with severe residual PR in native right ventricular outflow tract (RVOT). Patients with native RVOT and severe residual PR were selected on a case-by-case basis according to the anatomy feature of the patient and design of the valve. Patient demographics and preprocedural, intraprocedural, and follow-up data were reviewed. Four patients (2 females) with severe residual (grade 4+) were enrolled in this study with a mean age of 35.50 ± 5.67 years. Three patients had previous surgery for Tetralogy of Fallot and 1 for congenital pulmonary stenosis. All patients were symptomatic with New York Health Association heart function III at baseline. The inflow and outflow landing zone in these 4 patients was 41/39, 27/31, 27/31, and 28/30 mm, and 4 devices (44 mm/36 mm/36 mm/36 mm) were used for these patients, respectively. Successful valve implantation was achieved in all 4 patients. No device malposition, coronary obstruction, reduced flow to the pulmonary artery (PA) branches, and paravalvular leak were noted during the procedures. Mean PA diastolic pressure increased from 3.7 ± 1.5 to 16.5 ± 3.6 mmHg (p < 0.05). In 1 month follow-up, magnetic resonance imaging revealed positive right ventricular remodeling with right ventricular end-diastolic volume that decreased from 164.3 ± 5.5 to 89.8 ± 3.1 ml after intervention (p < 0.05) with the mean RVOT pressure gradient being 7 ± 0.7 mmHg. This first-in-man study demonstrates the initial safety and feasibility of the Med-Zenith PT valve in the treatment of severe PR. Dialysis-dependent patients undergoing aortic valve replacement (AVR) for aortic stenosis have poor short-term survival. Many patients who could benefit from AVR are deemed at elevated risk to undergo standard surgery. Transcatheter aortic valve replacement (TAVR) has proven to be a good option for these patients but there is little data on outcomes. Our goal was to assess morbidity and short-term mortality of dialysis-dependent patients who were deemed at elevated risk for surgery and underwent TAVR. A retrospective study of all dialysis-dependent patients undergoing TAVR over a 7-year period at 2 institutions was performed. Baseline characteristics, perioperative outcomes, and follow-up echocardiographic data were examined. Survival was determined using the Kaplan–Meier method. Variables are reported as mean ± standard deviation. Paired-samples t-test was used to determine the differences between continuous variables. Forty-seven patients, 31 (66%) of whom were male, underwent TAVR at 2 academic institutions during the 7-year period. Average age was 73.8 ± 9.1 years. Preoperative EuroScore II was 11.4% ± 8.2%. Forty-one of the 47 (87%) patients had NYHA class III or IV symptoms prior to TAVR. Twenty-six patients (55%) had peripheral vascular disease, 15/47 (32%) had chronic lung disease, and 29/47 (61%) had diabetes mellitus. Preoperative ejection fraction was 47.9% ± 16.7 %. Three patients (6%) suffered a postoperative stroke, 4 patients (9%) developed postoperative atrial fibrillation, and 2 patients (4%) had cardiac arrest. Seven patients (15%) died within 30 days. Survival at 1 and 2 years was 72% and 49%, respectively ( Figure PC67-1 ). By comparison, the 1- and 2-year survival for 237 patients on hemodialysis who underwent surgical AVR in the same time period was 64% and 55%, respectively. At a mean follow-up time of 12.1 ±11.1 months postoperatively, mean ejection fraction increased to 52.1 ± 14.1 (p = 0.016). Figure PC67-1. Survival analysis of dialysis-dependent patients who underwent transcatheter aortic valve replacement. Dialysis-dependent patients who had TAVR had poor operative and short-term survival. This was similar to patients who underwent surgical AVR. These poor short-term outcomes should temper enthusiasm for AVR, either transcatheter or surgical, in this patient population; careful patient selection is needed. A study to determine specific variables that dictate poor outcomes is warranted. Frailty is a geriatric syndrome frequently observed in elder-ly high-risk patients undergoing transcatheter aortic valve implantation (TAVI), which decreases the potential for functional recovery after TAVI and diminishes postoperative life expectancy. The study sought to develop a preprocedural frailty assessment based on parameters measured by a wearable health-monitoring device. The predictive performance of this multimodality frailty assessment (MFA) with respect to hospital mortality after TAVI was compared to conventional frailty scoring methods. A prospective cohort of elderly adults undergoing TAVI procedure via a transapical approach between December 2017 and December 2018 in a single center was included in the present study. Patients wore the device for 1 week prior to the procedure. Threshold levels in 3 categories (steps, heart rate range, and stress) were calculated with receiver operating characteristic analysis. The patients were assigned 1 point per category when exceeding the cutoff value and then classified in 4 stages (no, borderline, frail, and very frail). The MFA was then compared to gait speed category derived from 6-minute-walking-test (GSC) and the Edmonton Frailty Scale classification (EFS-C). The primary study endpoint was hospital mortality. In total, 36 patients with a mean age of 77.75 years (±5.1) were included. All-cause hospital mortality was 8.3% (n = 3). Depending on the frailty scores used, the prevalence of frailty ranged from 55.5% (MFA) and 60.6% (EFS-C) to 62.5% (GSC). Overall preprocedural stress level (p = 0.036), minutes of high stress per day (p = 0.042), minutes of rest per day (p = 0.034), and daily heart rate maximum (p = 0.036) as single parameters were the strongest predictors of hospital mortality. When comparing the different frailty scores, the MFA demonstrated the highest predictability of hospital mortality (MFA: AUC: 0.845 [0.657–1.000], p = 0.052; GSC: AUC: 0.730 [0.474–0.986], p = 0.196; EFS-C: AUC: 0.638 [0.265–1.000], p = 0.438). The preliminary findings of this study demonstrate the strong predictive performance of MFA compared to conventional frailty methods. The promising initial results warrant further evaluation of MFA as a predictor of short- and long-term mortality after transcatheter structural interventions or conventional surgery. Figure PC68-1. Comparison of the different frailty scores with ROC analysis. EFS-C: Edmonton Frailty Scale classification; MFA: multimodality frailty assessment; ROC: receiver operating characteristic. Transcatheter aortic valve replacement (TAVR) valve-in-valve (V-i-V) for homograft structural valve degeneration (SVD) is feasible, but should be implemented with caution, as the predominant homograft SVD mechanism is regurgitation. We present our concept of distributed, “aortic-to-ventricular” in-homograft fixation and outcomes of TAVR ViV for homograft vs. bioprostheses SVD. Between 2015 and 2017, 41 patients underwent TAVR ViV for the aortic valve prosthesis SVD. Of them, 33 patients presented with degenerated bioprostheses (TAVR-BP group) and 8 with homografts (TAVR-H group). The Valve Academic Research Consortium criteria were used for reporting purposes. Patients in TAVR-BP group were older (72.5 ± 15.1 years vs. 50.8 ± 16.7 years; p < 0.001) and 94% of them had prosthetic stenosis, compared to TAVR-H group (p = 0.002), while 88% of TAVR-H patients had aortic regurgitation (p ≤ 0.001). The Society of Thoracic Surgery score was 5.7% ± 3.7% in TAVR-BP vs. 1.9% ± 0.6% in TAVR-H group, p = 0.006. TAVR-H patients received Sapien-3 (6), Sapien-XT (1), and CoreValve (1) devices. Deep, 30%–40% ventricular fixation was attempted to anchor the prosthesis on the homograft suture line. In the entire cohort, there was zero 30-day mortality and stroke. One TAVR-BP patient experienced distal prosthesis migration and type-B aortic dissection, treated with immediate transcatheter endovascular aortic repair. First-attempt device implantation was successful in 26 (78%) TAVR-BP and in 7 (87%) TAVR-H patients. In 3 (9%) TAVR-BP individuals, a second device was used. No patient required pacemaker implantation. In 2 TAVR-H patients with preoperative homograft regurgitation, a moderate paravalvular leak (PVL) occurred in mid-term follow-up. In both of them, extensive, 60% ventricular fixation led to mismatch between fixation points and homograft suture line. Recent imaging revealed progressive device migration in 1 patient. There were no differences in perioperative (19.5 ± 8.9 mmHg vs. 19.1 ± 5.5 mmHg, p = 0.92) and mid-term follow-up transvalvular gradients (18.2 ± 7.5 mmHg vs. 17.9 ± 5.0 mmHg, p = 0.91) between groups. Aortic regurgitation was the predominant homograft SVD mechanism. However, lack of calcification did not cause perioperative prosthesis migration. TAVR ViV in regurgitant homograft can be safely implanted provided that the prosthesis fixation points match the homograft suture line. Precise, 30%–40% ventricular device positioning is crucial for procedural success and avoidance of PVL/late prosthesis migration. Figure PC69-1. We report a fully endoscopic implantation of a Sapien 3 transcatheter prosthesis, which was used to treat a high-risk patient with severe mitral valve disease and mitral annular calcification (MAC). This technique has all the advantages of the already reported full sternotomy transatrial technique plus the added advantage of the minimally invasive approach through a 3-cm periareolar incision and the more precise transcatheter valve placement due to the excellent stereoscopic vision available today through the three-dimensional (3D) endoscopes. A 61-year-old lady was admitted with pulmonary edema. She had a history of chronic renal failure on dialysis and aortic valve replacement with a mechanical prosthesis 4 years ago. A transesophageal echocardiography showed torrential mitral valve regurgitation because of immobile and calcified posterior leaflet and extended MAC. Preoperative computed tomography scan confirmed extensive calcification of the ascending aorta, the aortic annulus, and severe MAC, which was forming an incomplete ring. Her Society of Thoracic Surgery mortality score was calculated as 19.1%. The patient was also not a candidate for a transapical or transfemoral transcatheter mitral valve replacement due to the risk of left ventricular outflow tract obstruction (LVOT). Therefore, a hybrid endoscopic approach was offered to the patient. The chest was entered through a 3-cm right periareolar incision, in the 4th intercostal space. On full cardiopulmonary bypass, a left atriotomy was performed and the anterior mitral leaflet was excised and 3 anchoring annular sutures inserted at 12, 4, and 8 o’ clock. The annulus was sized with a 26-mm balloon and a 26-mm Sapien 3 valve was positioned and inflated under 3D endoscopic vision, with care taken that the skirt of the valve was sitting against the annulus. Then the three anchoring sutures were passed through the stent and secured. Postoperative TEE confirmed excellent function of the Sapien 3, without any paravalvular leaks or LVOT obstruction. The patient was extubated on the 2nd postoperative day and had an uneventful recovery. She remains well and in class II 8 months after her discharge with normal Sapien 3 function on echocardiogram. Acute heart failure is known to be the most frequent cause of hospital readmission after transcatheter aortic valve implantation (TAVI). Furthermore, it is associated with an increased risk of mortality. The aim of the study was to define independent predictors for acute heart failure after TAVI. From 2008 to 2017, 298 patients with isolated aortic stenosis undergoing either transfemoral or transapical TAVI were included in this single-center study. The primary study endpoint was defined as hospital readmission due to acute heart failure. All analyses were performed as time-to-first-event analysis. Stepwise multivariable Cox regression analysis was used to determine independent predictors for acute heart failure. Society of Thoracic Surgery (STS) score >4.6% (hazard ratio [HR] 2.481, 95% confidence interval [CI] 1.331–4.622, p = 0.004) and HS-Troponin T >23.3 pg/ml (HR 2.892, 95% CI 1.434–5.829, p = 0.003) were significant prognostic factors after multivariate cox regression. NT-proBNP >2,762 pg/ml (HR 1.708, 95% CI 0.909–3.208, p = 0.096) and mean gradient >45 mmHg (HR 0.661, 95% CI 0.363–1.206, p = 0.117) were significant in univariate analysis, but not in multivariate regression analysis. STS score and highly sensitive Troponin T are independent predictors for acute heart failure after TAVI. N-terminal prohormone of brain natriuretic peptide seems to be less accurate as a risk factor for heart failure after TAVI. Tetralogy of Fallot is corrected conservatively through median sternotomy universally. We have series of patients undergoing total correction for the same through minimally invasive incisions. Significant improvement in overall performance of patients in the postoperative period. In trained hands minimally invasive intracardiac repair for Tetralogy is feasible and reproducible by junior surgeons. In congenital heart disease patients, access to the pulmonary artery and pulmonary valve has traditionally been accomplished via median sternotomy or thoracotomy. Given the complex anatomy involved in congenital heart surgery and the frequent need for redo surgery, a minimally invasive approach to the pulmonary artery is desirable. We devised a minimally invasive and less-morbid surgical approach to the pulmonary artery utilizing a minithoracotomy and an innovative surgical device. Peripheral arterial cannulation and dual peripheral venous cannulation utilizing the femoral and internal jugular veins is employed. A left-sided 5 cm transverse, rib-sparing minithoracotomy is placed in either the 3rd intercostal space for pulmonary valve access or the 2nd intercostal space for distal pulmonary artery access. For pulmonary valve replacement (PVR) an automated dual-curved needle suturing device is used to place 3.5-mm-wide horizontal mattress sutures along the posterior wall, while the rest of the procedure uses hand-sewn technique and an anterior pulmonary artery polytetrafluoroethylene patch to augment the right ventricular outflow tract. Our minithoracotomy approach was initiated in July 2018 and to date has been used in 7 patients, all males so far, and ranging in age from 12 to 48 years. We have performed 4 successful PVRs, 1 PVR that was converted to an open procedure, 1 plication of the main pulmonary artery for Melody valve deployment, and 1 pulmonary artery translocation for anomalous aortic origin of the left coronary artery. Our approach provides a safe, versatile, and less-morbid method for surgically accessing the pulmonary artery and pulmonary valve. Unroofed coronary sinus syndrome (UCS), also known as coronary sinus atrial septal defect, is a rare congenital cardiac anomaly. We performed UCS repair and tricuspid annuloplasty under totally three-dimensional (3D) endoscopic vision. We utilized three-port system (1 inch main working port, camera port, and left-hand port) without robotic assistance. Both left and right atrium were entered. The UCS opening in the left atrium was closed with bovine pericardial patch. Totally 3D endoscopic repair for UCS is a safe and effective procedure. Right ventricular (RV) failure severely compromises the prognosis of many congenital heart disease (CHD) children. However, little is known about how RV failure is epigenetically regulated. Here we used CHD-associated RV failure model, neonatal rat pulmonary arterial banding (PAB), and the most common cyanotic CHD, Tetralogy of Fallot (TOF), to reveal the role of histone transferase CBP/p300 in the control of transverse tubules (T-tubules) of RV cardiomyocytes. Figure PC75-1. PAB performed on P0 significantly increased RV afterload, which induced RV hypertrophy on P7 and RV failure on P28. Compared with normal RV, RV with heart failure displayed reduced T-tubules and T-tubules-associated genes JPH2, Cav3. Calcium imaging indicated that contraction amplitude of RV cardiomyocytes significantly decreased and time to peak increased. Similar results were found in the cardiomyocytes of TOF. Lower expression of histone transferases CBP/p300 and H3K27ac were observed both in PAB-induced RV and TOF hearts. Mosaic deletion of CBP/p300 with AAV-cTnT-Cre in RV resulted in lower expression of H3K27ac in RV cardiomyocytes, loss of T-tubules and T-tubules-associated genes, and the contraction ability of cardiomyocytes. Histone transferases CBP/p300 directly regulated T-tubules of RV cardiomyocytes and its histone transferase activity plays an important role in the maintenance of T-tubules in the process of CHD RV failure development. Partial, incomplete, atrioventricular septal defect is a prevalent congenital disorder and must be researched by aiming to reach a surgical technique with minimal invasiveness and best results possible. To report the case of a 10-year-old female patient with partial defect of the atrioventricular septum, with consequent damage in the execution of their daily activities, whose correction was made by means of the surgical technique minimally invasive thoracoscopy. The ostium primum-type atrial septal defect (ASD) results from the abnormality of the cushions atrioventricular, poor embryological formation, with difficulties of anchoring the atrial septa, and may be associated with other anomalies due to defects in the cushions, such as septal leaflet fissure of the mitral valve known as a cleft as in the case in question. The therapeutic option of choice was surgical correction through the use of thoracoscopy, which enabled the procedure without direct vision and without sternotomy. The procedure was conducted with no accidents, and cardiopulmonary bypass (CPB) was conducted using a jugular, femoral, femoral cannulation and a 2 in incision posterior of the midclavicular line on the 4th intercostal space. The total CPB was 60 minutes and aortic cross-clamp 45 minutes. There was minimal blood loss and the repair of the mitral cleft was done using separate stiches and a pericardial patch for the ASD closure. The patient stayed in intensive care unit (ICU) for 18 hours and after removing the thoracic drain she was discharged to the ward. There was only 150 ml of drainage volume. On the 3rd postoperative day she was discharged home. She was cleared to all her normal activities without any restriction on postoperative day 10. This technique permits less aggression to the patient, allowing in some cases extubation of the patient still inside the operating room, right before being referred to ICU, known as FAST TRACK. In addition to that are a notably lower inflammatory response, lower intra- and postoperative bleeding, with consequent reduction of ICU and hospital length of stay. To evaluate the early results of totally endoscopic closure of ventricular septal defect (VSD) in Vietnam. Totally endoscopic VSD closure was performed in 8 patients (3 children and 5 adults). All patients were diagnosed with perimembranous VSD in which 5 patients had right ventricular outflow tract stenosis. We used 3 trocarts of 5 mm and 1 trocart of 12 mm in the right chest, using peripheral cannulation for cardiopulmonary bypass, bicaval occlusion, Chitwood aortic clamp, right atriotomy, and closing VSD by endoscopy without a robotically assisted surgical system. No postoperative complications and deaths. Mean ± standard deviation of cardiopulmonary bypass time and aortic clamping time were 70 ± 23.6 and 50.6 ± 25.3 minutes. The mean mechanical ventilation time was 1.2 ± 0.3 hours. Patients were hospitalized for 5.8 days and could resume normal activities after 1 week. Totally endoscopic closure of VSD without robotic assistance is feasible and safe, with a small surgical scar and high esthetics. Myo-myectomy for hypertrophic obstructive cardiomyopathy (HOCM) through aortic valve had limitations such as limited operative view, risk of aortic valve damage, and insufficient muscle resection. Via left atrial (transmitral) approach can provide an opportunity for mitral valve repair/replacement for mitral regurgitation. Six patients (6–73 years old) had myo-myectomy for diffuse subaortic obstruction of HOCM with our approach. Three had mitral valve repair and 3 had mitral valve replacement. Every case had relief of obstruction and symptom (left ventricular outflow tract gradient; 5~26 mmHg). Our approach could provide a wide view of subaortic region and lower portion of the septum and adequate operative view for those with diffuse type of HOCM. Figure PC78-1. Myo-mectomy for subaortic obstruction through mitral annulus. The purpose of this study was to evaluate the safety and efficacy of direct intralesional diode laser vaporization for venous malformations (VMs) with oroparyngeal involvement after a temporary tracheotomy. A retrospective assessment was carried out to evaluate the efficacy of direct intralesional diode laser vaporization on 21 consecutive patients presenting with extensive VMs involving the oropharynx in the head and neck and who had undergone tracheotomy. Of the 21 patients, 4 were treated once and 17 were treated from 2 to 5 times. The duration of follow-up was, on average, 9.1 months. Of the 21 patients, 11 (53.3%) had complete palliation, whereas the rest (46.7%) achieved partial palliation. Minor complications occurred in 12 of the 21 patients. Direct intralesional diode laser vaporization after a temporary tracheotomy is a safe and effective treatment for extensive VMs involving oropharyngeal areas of the head and neck.
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