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, , Homa Yousefi Khoshsabeghe
Published: 1 January 2013
Abstract:
Public health facilities in Iran are exposed to a wide range of natural hazards. This article presents the first survey of the impacts of such natural hazards on primary health care (PHC) centers in Iran from 2001 to 2011. A retrospective survey was conducted in 25 out of 30 provinces of Iran. Archival reports at provincial public health departments were cross-referenced with key informant interviews. During a 10-year period, 119 natural hazard events were recorded that led to physical damage and/or functional failure in 1,401 health centers, 127 deaths and injury or illness in 644 health staff. Earthquakes accounted for the most physical damage and all health-worker deaths. However, there was an increasing trend of impacts due to hydro-meteorological hazards. Iran’s health system needs to establish a registry to track the impact of natural hazards on health facilities, conduct regular hazard and vulnerability assessments and increase mitigation and preparedness measures. Keywords: Disaster, primary health care, facility, Iran, natural hazard Corresponding author: Ali Ardalan MD, PhD. Iran’s National Institute of Health Research, Tehran University of Medical Sciences. Harvard Humanitarian Initiative. Email: [email protected]
, , Bert Vanmechelen, , Erik Verbeken, ,
PLOS Neglected Tropical Diseases, Volume 11; https://doi.org/10.1371/journal.pntd.0006042

Abstract:
Hantavirus, the hemorrhagic causative agent of two clinical diseases, is found worldwide with variation in severity, incidence and mortality. The most lethal hantaviruses are found on the American continent where the most prevalent viruses like Andes virus and Sin Nombre virus are known to cause hantavirus pulmonary syndrome. New World hantavirus infection of immunocompetent hamsters results in an asymptomatic infection except for Andes virus and Maporal virus; the only hantaviruses causing a lethal disease in immunocompetent Syrian hamsters mimicking hantavirus pulmonary syndrome in humans. Hamsters, immunosuppressed with dexamethasone and cyclophosphamide, were infected intramuscularly with different New World hantavirus strains (Bayou virus, Black Creek Canal virus, Caño Delgadito virus, Choclo virus, Laguna Negra virus, and Maporal virus). In the present study, we show that immunosuppression of hamsters followed by infection with a New World hantavirus results in an acute disease that precisely mimics both hantavirus disease in humans and Andes virus infection of hamsters. Infected hamsters showed specific clinical signs of disease and moreover, histological analysis of lung tissue showed signs of pulmonary edema and inflammation within alveolar septa. In this study, we were able to infect immunosuppressed hamsters with different New World hantaviruses reaching a lethal outcome with signs of disease mimicking human disease. Hemorrhagic fever viruses have become of much greater importance in recent years. The more prominent presence of these viruses in a day-to-day setting and their impact on global health has had a positive impact on studying these viruses. Resolving their disease mechanisms and ways to intervene in their replication and associated health burden will stay a challenge for the upcoming decades. This challenge also counts for hantavirus, an emerging zoonosis. No vaccine or antiviral treatment is WHO prequalified or has shown to elicit a good protective or therapeutic antiviral response in humans. One of the main reasons is the lack of good animal disease models and the research focusing on this topic. Without a representative model, it is difficult to investigate new potential drugs. Within this setting we focused on establishing a disease model for the most prominent New World hantaviruses.
, Glenn Vinnicombe
PLOS Computational Biology, Volume 13; https://doi.org/10.1371/journal.pcbi.1005687

Abstract:
Noise is a prevalent and sometimes even dominant aspect of many biological processes. While many natural systems have adapted to attenuate or even usefully integrate noise, the variability it introduces often still delimits the achievable precision across biological functions. This is particularly so for visual phototransduction, the process responsible for converting photons of light into usable electrical signals (quantum bumps). Here, randomness of both the photon inputs (regarded as extrinsic noise) and the conversion process (intrinsic noise) are seen as two distinct, independent and significant limitations on visual reliability. Past research has attempted to quantify the relative effects of these noise sources by using approximate methods that do not fully account for the discrete, point process and time ordered nature of the problem. As a result the conclusions drawn from these different approaches have led to inconsistent expositions of phototransduction noise performance. This paper provides a fresh and complete analysis of the relative impact of intrinsic and extrinsic noise in invertebrate phototransduction using minimum mean squared error reconstruction techniques based on Bayesian point process (Snyder) filters. An integrate-fire based algorithm is developed to reliably estimate photon times from quantum bumps and Snyder filters are then used to causally estimate random light intensities both at the front and back end of the phototransduction cascade. Comparison of these estimates reveals that the dominant noise source transitions from extrinsic to intrinsic as light intensity increases. By extending the filtering techniques to account for delays, it is further found that among the intrinsic noise components, which include bump latency (mean delay and jitter) and shape (amplitude and width) variance, it is the mean delay that is critical to noise performance. As the timeliness of visual information is important for real-time action, this delay could potentially limit the speed at which invertebrates can respond to stimuli. Consequently, if one wants to increase visual fidelity, reducing the photoconversion lag is much more important than improving the regularity of the electrical signal. The invertebrate phototransduction system captures and converts environmental light inputs into electrical signals for use in later visual processing. Consequently, one would expect it to be optimised in some way to ensure that only a minimal amount of environmental information is lost during conversion. Confirming this requires an understanding and quantification of the performance limiting noise sources. Photons, which are inherently random and discrete, introduce extrinsic noise. The phototransduction cascade, which converts photons into electrical bumps possessing non-deterministic shapes and latencies, contributes intrinsic noise. Previous work on characterising the relative impact of all these sources did not account for the discrete, causal, point process nature of the problem and thus results were often inconclusive. Here we use non-linear Poisson process filtering to show that photon noise is dominant at low light intensity and cascade noise limiting at high intensity. Further, our analysis reveals that mean bump delay is the most deleterious aspect of the intrinsic noise. Our work emphasises a new approach to assessing sensory noise and provides the first complete description and evaluation of the relative impact of noise in phototransduction that does not rely on continuity, linearity or Gaussian approximations.
Ping Li, , Huamei Yue, Chuangju Li, Hao Du, Xinmei Qiao, Zhigang Liu, Qiong Zhou,
Published: 27 October 2017
Abstract:
Conventional sperm analysis (i.e., motility and fertility) has been used to evaluate sperm quality. Understanding the quality of sperm on the molecular level in the sturgeons, Acipenser baerii and A. schrenckii, is essential for the improvement of the conservation of genetic resources and farming performance. In this study, we used the iTRAQ proteomics approach to perform proteomic profiling of spermatozoa associated with sperm quality in sturgeons (Data are available via ProteomeXchange with identifier PXD006108). The results showed 291 and 359 differentially expressed proteins in A. baerii and A. schrenckii, respectively, of which 72 were common to both species and all were upregulated in high quality compared with low quality samples. The differentially expressed proteins were mainly categorized into the generation of precursor metabolites and energy and oxidation, and they were localized to the mitochondria. Three distinguishing pathways, Arginine and proline metabolism, Pyruvate metabolism and the Citrate cycle (TCA cycle) were found to play an important role in energy metabolism, and some substrates could be used in the sperm medium for storage and cryopreservation. The quantity levels of two proteins, CKMT1 and LDHB, were verified by western blot analysis. Moreover, other potential biomarkers involved in oxidation reduction, ubiquitin-proteasome-dependent proteolysis, chaperones and binding activity were also discussed. Our study is the first to use the iTRAQ-based proteomics approach to analyse the sturgeon spermatozoa proteome, and the results that we obtained are valuable for the prediction of sperm quality and reproduction management in these threatened species.
Yang Xu, Wenli Zhao, Te Li, Ye Zhao, , Shilin Song
Published: 27 October 2017
Abstract:
Endometriosis is a multifactorial, oestrogen-dependent, inflammatory, gynaecological condition that can result in long-lasting visceral pelvic pain and infertility. Acupuncture could be an effective treatment for endometriosis and may relieve pain. Our aim in the present study was to determine the effectiveness of acupuncture as a treatment for endometriosis-related pain. In December 2016, six databases were searched for randomised controlled trials that determined the effectiveness of acupuncture in the treatment of endometriosis-related pain. Ultimately, 10 studies involving 589 patients were included. The main outcomes assessed were variation in pain level, variation in peripheral blood CA-125 level, and clinical effective rate. All analyses were performed using comprehensive meta-analysis statistical software. Of the 10 studies included, only one pilot study used a placebo control and assessed blinding; the rest used various controls (medications and herbs), which were impossible to blind. The sample sizes were small in all studies, ranging from 8 to 36 patients per arm. The mean difference (MD) in pain reduction (pre- minus post-interventional pain level—measured on a 0–10-point scale) between the acupuncture and control groups was 1.36 (95% confidence intervals [CI] = 1.01–1.72, P<0.0001). Acupuncture had a positive effect on peripheral blood CA-125 levels, as compared with the control groups (MD = 5.9, 95% CI = 1.56–10.25, P = 0.008). Similarly, the effect of acupuncture on clinical effective rate was positive, as compared with the control groups (odds ratio = 2.07; 95% CI = 1.24–3.44, P = 0.005). Few randomised, blinded clinical trials have addressed the efficacy of acupuncture in treating endometriosis-related pain. Nonetheless, the current literature suggests that acupuncture reduces pain and serum CA-125 levels, regardless of the control intervention used. To confirm these findings, additional, blinded studies with proper controls and adequate sample sizes are needed.
, Birthe Heitkötter, , Christoph Schliemann, , , Alessandro Marra, Ludger Hillejan, Michael Mohr, Georg Evers, et al.
Published: 27 October 2017
Abstract:
PSMA (prostate-specific membrane antigen) is overexpressed in prostate cancer cells and is reported to be a promising target for antibody-based radioligand therapy in patients with metastasized prostate cancer. Since PSMA expression is not restricted to prostate cancer, the underlying study investigates PSMA expression in non-small cell lung cancer (NSCLC). Immunohistochemistry was used to identify PSMA expression in n = 275 samples of NSCLC tissue specimens. By means of CD34 co-expression, the level of PSMA expression in tumor associated neovasculature was investigated. The impact of PSMA expression on clinicopathologic parameters and prognosis was evaluated. PSMA tumor cell expression in NSCLC is as low as 6% and was predominantly found in squamous cell carcinoma (p = 0.002). Neovascular PSMA expression was found in 49% of NSCLC. High neovascular PSMA expression was associated with higher tumor grading (G3/G4) (p < 0.001). Neither for PSMA tumor cell expression, nor for PSMA neovascular cell expression prognostic effects were found for the investigated NSCLC cases. Here, we report on the expression of PSMA in NSCLC tissue samples. Against the background of a potential treatment with radiolabeled PSMA ligands, our data might serve for the future identification of patients who could benefit from this therapeutic option.
, , Jean-Luc Bonnet, Christine Henry, Alain Belo, Philippe Mabo, Guy Carrault, Alfredo I. Hernández
Published: 27 October 2017
Abstract:
Vagus nerve stimulation (VNS) is an established adjunctive therapy for pharmacologically refractory epilepsy and depression and is currently in active clinical research for other applications. In current clinical studies, VNS is delivered in an open-loop approach, where VNS parameters are defined during a manual titration phase. However, the physiological response to a given VNS configuration shows significant inter and intra-patient variability and may significantly evolve through time. VNS closed-loop approaches, allowing for the optimization of the therapy in an adaptive manner, may be necessary to improve efficacy while reducing side effects. This paper proposes a generic, closed-loop control VNS system that is able to optimize a number of VNS parameters in an adaptive fashion, in order to keep a control variable within a specified range. Although the proposed control method is completely generic, an example application using the cardiac beat to beat interval (RR) as control variable will be developed in this paper. The proposed controller is based on a state transition model (STM) that can be configured using a partially or a fully-connected architecture, different model orders and different state-transition algorithms. The controller is applied to the adaptive regulation of heart rate and evaluated on 6 sheep, for 13 different targets, using partially-connected STM with 10 states. Also, partially and fully-connected STM defined by 30 states were applied to 7 other sheep for the same 10 targets. Results illustrate the interest of the proposed fully-connected STM and the feasibility of integrating this control system into an implantable neuromodulator.
D. Cooper Campbell,
Published: 27 October 2017
Abstract:
North America’s Great Basin has long been of interest to biologists due to its high level of organismal endemicity throughout its endorheic watersheds. One example of such a group is the subfamily Empetricthyinae. In this paper, we analyzed the relationships of the Empetrichtyinae and assessed the validity of the subspecies designations given by Williams and Wilde within the group using concatenated phylogenetic tree estimation and species tree estimation. Samples from 19 populations were included covering the entire distribution of the three extant species of Empetricthyinae–Crenichthys nevadae, Crenichthys baileyi and Empetricthys latos. Three nuclear introns (S8 intron 4, S7 intron 1, and P0 intron 1) and one mitochondrial gene (Cytb) were sequenced for phylogenetic analysis. Using these sequences, we generated two separate hypotheses of the evolutionary relationships of Empetrichtyinae- one based on the mitochondrial data and one based on the nuclear data using Bayesian phylogenetics. Haplotype networks were also generated to look at the relationships of the populations within Empetrichthyinae. After comparing the two phylogenetic hypotheses, species trees were generated using *BEAST with the nuclear data to further test the validity of the subspecies within Empetrichthyinae. The mitochondrial analyses supported four lineages within C. baileyi and 2 within C. nevadae. The concatenated nuclear tree was more conserved, supporting one clade and an unresolved polytomy in both species. The species tree analysis supported the presence of two species within both C. baileyi and C. nevadae. Based on the results of these analyses, the subspecies designations of Williams and Wilde are not valid, rather a conservative approach suggests there are two species within C. nevadae and two species within C. baileyi. No structure was found for E. latos or the populations of Empetricthyinae. This study represents one of many demonstrating the invalidity of subspecies and their detriment to species identification, conservation, and understanding.
, , Rula Ghandour, Suzan Mitwalli, Shiraz Nasr, , Rita Giacaman
Published: 27 October 2017
Abstract:
The links between two commonly used measures of health—self-rated health (SRH) and self-reported illness (SRI)–and socio-economic and contextual factors are poorly understood in Low and Middle Income Countries (LMICs) and more specifically among women in conflict areas. This study assesses the socioeconomic determinants of three self-reported measures of health among women in the occupied Palestinian territories; self-reported self-rated health (SRH) and two self-reported illness indicators (acute and chronic diseases). Data were obtained from the 2010 Palestinian Family Health Survey (PFHS), providing a sample of 14,819 women aged 15–54. Data were used to construct three binary dependent variable—SRH (poor or otherwise), and reporting two SRI indicators—general illness and chronic illness (yes or otherwise). Multilevel logistic regression models for each dependent variable were estimated, with individual level socioeconomic and sociodemographic predictors and random intercepts at the governorate and community level included, to explore the determinants of inequalities in health. Consistent socioeconomic inequalities in women’s reports of both SRH and SRI are found. Better educated, wealthier women are significantly less likely to report an SRI and poor SRH. However, intra-oPt regional disparities are not consistent across SRH and SRI. Women from the Gaza Strip are less likely to report poor SRH compared to women from all other regions in the West Bank. Geographic and residential factors, together with socioeconomic status, are key to understanding differences between women’s reports of SRI and SRH in the oPt. More evidence is needed on the health of women in the oPt beyond the ages currently included in surveys. The results for SRH show discrepancies which can often occur in conflict affected settings where a combination of ill-health and poor access to health services impact on women’s health. These results indicate that future policies should be developed in a holistic manner by targeting physical and mental health and well-being in programmes addressing the health needs of women, especially those in conflict affected zones.
Ryan T. Philips, Mriganka Sur,
PLOS Computational Biology, Volume 13; https://doi.org/10.1371/journal.pcbi.1005785

Abstract:
Orientation preference maps (OPMs) are present in carnivores (such as cats and ferrets) and primates but are absent in rodents. In this study we investigate the possible link between astrocyte arbors and presence of OPMs. We simulate the development of orientation maps with varying hypercolumn widths using a variant of the Laterally Interconnected Synergetically Self-Organizing Map (LISSOM) model, the Gain Control Adaptive Laterally connected (GCAL) model, with an additional layer simulating astrocytic activation. The synaptic activity of V1 neurons is given as input to the astrocyte layer. The activity of this astrocyte layer is now used to modulate bidirectional plasticity of lateral excitatory connections in the V1 layer. By simply varying the radius of the astrocytes, the extent of lateral excitatory neuronal connections can be manipulated. An increase in the radius of lateral excitatory connections subsequently increases the size of a single hypercolumn in the OPM. When these lateral excitatory connections become small enough the OPM disappears and a salt-and-pepper organization emerges. Columns of neurons in the primary visual cortex (V1) are known to be tuned to visual stimuli containing edges of a particular orientation. The arrangement of these cortical columns varies across species. In many species such as in ferrets, cats, and monkeys a topology preserving map is observed, wherein similarly tuned columns are observed in close proximity to each other, resulting in the formation of Orientation Preference Maps (OPMs). The width of the hypercolumns, the fundamental unit of an OPM, also varies across species. However, such an arrangement is not observed in rodents, wherein a more random arrangement of these cortical columns is reported. We explore the role of astrocytes in the arrangement of these cortical columns using a self-organizing computational model. Invoking evidence that astrocytes could influence bidirectional plasticity among effective lateral excitatory connections in V1, we introduce a mechanism by which astrocytic inputs can influence map formation in the neuronal network. In the resulting model-generated OPMs the radius of the hypercolumns is found to be correlated with that of astrocytic arbors, a feature that finds support in experimental studies.
Helene M. Wolsk, , Augusto A. Litonjua, Bruce W. Hollis, Johannes Waage, , , ,
Published: 27 October 2017
Abstract:
We recently published two independent randomized controlled trials of vitamin D supplementation during pregnancy, both indicating a >20% reduced risk of asthma/recurrent wheeze in the offspring by 3 years of age. However, neither reached statistical significance. To perform a combined analysis of the two trials and investigate whether maternal 25-hydroxy-vitamin D (25(OH)D) level at trial entry modified the intervention effect. VDAART (N = 806) and COPSAC2010. (N = 581) randomized pregnant women to daily high-dose vitamin D3 (4,000 IU/d and 2,400 IU/d, respectively) or placebo. All women also received a prenatal vitamin containing 400 IU/d vitamin D3. The primary outcome was asthma/recurrent wheeze from 0-3yrs. Secondary end-points were specific IgE, total IgE, eczema and lower respiratory tract infections (LRTI). We conducted random effects combined analyses of the treatment effect, individual patient data (IPD) meta-analyses, and analyses stratified by 25(OH)D level at study entry. The analysis showed a 25% reduced risk of asthma/recurrent wheeze at 0-3yrs: adjusted odds ratio (aOR) = 0.74 (95% CI, 0.57–0.96), p = 0.02. The effect was strongest among women with 25(OH)D level ≥30ng/ml at study entry: aOR = 0.54 (0.33–0.88), p = 0.01, whereas no significant effect was observed among women with 25(OH)D level <30ng/ml at study entry: aOR = 0.84 (0.62–1.15), p = 0.25. The IPD meta-analyses showed similar results. There was no effect on the secondary end-points. This combined analysis shows that vitamin D supplementation during pregnancy results in a significant reduced risk of asthma/recurrent wheeze in the offspring, especially among women with 25(OH)D level ≥ 30 ng/ml at randomization, where the risk was almost halved. Future studies should examine the possibility of raising 25(OH)D levels to at least 30 ng/ml early in pregnancy or using higher doses than used in our studies. COPSAC2010: ClinicalTrials.gov NCT00856947; VDAART: ClinicalTrials.gov NCT00920621
, , Gustavo C. Cerqueira, , Timothy J. C. Anderson, Kanlaya Sriprawat, , , Daniel E. Neafsey, Caroline O. Buckee
Published: 27 October 2017
Abstract:
With the rapidly increasing abundance and accessibility of genomic data, there is a growing interest in using population genetic approaches to characterize fine-scale dispersal of organisms, providing insight into biological processes across a broad range of fields including ecology, evolution and epidemiology. For sexually recombining haploid organisms such as the human malaria parasite P. falciparum, however, there have been no systematic assessments of the type of data and methods required to resolve fine scale connectivity. This analytical gap hinders the use of genomics for understanding local transmission patterns, a crucial goal for policy makers charged with eliminating this important human pathogen. Here we use data collected from four clinics with a catchment area spanning approximately 120 km of the Thai-Myanmar border to compare the ability of divergence (FST) and relatedness based on identity by descent (IBD) to resolve spatial connectivity between malaria parasites collected from proximal clinics. We found no relationship between inter-clinic distance and FST, likely due to sampling of highly related parasites within clinics, but a significant decline in IBD-based relatedness with increasing inter-clinic distance. This association was contingent upon the data set type and size. We estimated that approximately 147 single-infection whole genome sequenced parasite samples or 222 single-infection parasite samples genotyped at 93 single nucleotide polymorphisms (SNPs) were sufficient to recover a robust spatial trend estimate at this scale. In summary, surveillance efforts cannot rely on classical measures of genetic divergence to measure P. falciparum transmission on a local scale. Given adequate sampling, IBD-based relatedness provides a useful alternative, and robust trends can be obtained from parasite samples genotyped at approximately 100 SNPs. The spatiotemporal dispersal of organisms can inform efforts to conserve endangered species, to contain the spread of drug resistance, and to eliminate disease. As genomic data become increasingly more affordable and accessible via public depositories, the demand for methods capable of extracting fine-scale population structure from genomic data grows. However, to the best of our knowledge, there are no guidelines regarding the type of data and methods required to resolve local spatial trends over sexually recombining haploid organisms, such as the malaria parasite. The approach we present here compares relatedness based on identity by descent, which accounts for recombination while distinguishing genetic identity due to inheritance from genetic identity due to chance, to a classic population genetic measure of divergence, using data from sexually recombining malaria parasites. Using identity by descent, we uncover a significant decrease in highly related malaria parasites collected from proximal clinics on the Thai-Myanmar border, a region where human mobility is high. Our results demonstrate the power of analyses based on identity by descent to detect recent and local trends. Similar analyses could be used to inform the molecular epidemiology of other sexually recombining organisms.
, Debananda Padhy, Prity Sahay, Amiya Pradhan, Sarada Sarangi, Gopinath Das, Niranjan Raj
Published: 27 October 2017
Abstract:
To evaluate different clinical variants of pseudoexfoliation syndrome and their risk of developing ocular hypertension (OHT) or glaucoma (PXG) Cross sectional hospital based study. All patients seen at glaucoma services of a tertiary eye care center in east India. Electronic medical records search of hospital database including consecutive new and old cases seen during April 2013 to March 2015 was done to retrieve case sensitive words including pseudoexfoliation, PXF, PEX, PXG and pseudoexfoliative glaucoma over any part of the clinical electronic sheet of the patient. All demographic and clinical details including laterality, the pattern of deposits, need for medicines and disc damage at presentation was compared in eyes with radial pigmentary, classical or combined forms of PXF phenotypes. Of 110313 PXF patients seen during the period of 2013–2015, a total of 2297 eyes of 1150 PXF patients were identified including 525 unilateral PXF (meaning a total of 1775 PXF eyes with 625 patients having bilateral disease, n = 1250 eyes, other clinically normal eye, n = 522) at presentation. Of 525 unilateral PXF eyes, 105 had OHT and 131 had glaucoma while bilateral cases had more >50% (675 eyes of 1250 eyes) with glaucoma. Glaucoma with significant changes in IOP with or without disc damage was seen in 32% of pigmentary and 39% of classical PXF forms with eyes with combined forms of PXF having around 50% with glaucoma at presentation compared to other forms, p<0.001. Different phenotypic variants of PXF in this Indian cohort was associated with 30–50% risk of OHT or glaucoma respectively. Adequate care is required while examining the pattern of PXF in each case to prognosticate each patient/eye.
Astrid Marot, Jean Henrion, , Christophe Moreno,
Published: 27 October 2017
Abstract:
Cirrhosis is a heterogeneous clinical condition that includes patients at wide-ranging stages of severity. The role of the underlying liver disease on patient prognosis remains unclear. To assess the impact of the underlying liver disease on the occurrence of hepatocellular carcinoma (HCC) and death. Data related to the occurrence of HCC and death were collected during a 21-year period among patients with cirrhosis related to alcoholic liver disease (ALD) (n = 529), chronic hepatitis C virus (HCV) infection (n = 145) or non-alcoholic fatty liver disease (NAFLD) (n = 78). At inclusion, ALD patients were younger than HCV and NAFLD patients (56 vs. 67 vs. 63 years; p<0.001) and had worse liver function (percent of patients with Child-Pugh stages B or C: 48% vs. 8% vs. 17%; p<0.001). During follow-up, 85 patients developed HCC and 379 died. The 10-year cumulative incidence rate of HCC was lower in ALD patients than in HCV and NAFLD patients (8.4% vs. 22.0% vs. 23.7%; p<0.001). The 10-year cumulative incidence rates of mortality were not statistically different between ALD, HCV and NAFLD patients (58.1% vs. 47.7% vs. 49.9%; p = 0.078). Alcohol abstinence and viral eradication were associated with reduced mortality among ALD and HCV patients, respectively. In multivariate analyses, ALD was associated with a reduced risk of HCC (0.39; 95% CI, 0.20–0.76; p = 0.005) but with a higher risk of mortality (1.53; 95% CI, 1.20–1.95; p<0.001). ALD patients died more frequently from decompensation of cirrhosis. Despite a lower incidence of HCC, patients with ALD-related cirrhosis have a worse outcome than those with chronic HCV infection or NAFLD-related cirrhosis.
Xiaoxiao Zhang, , Yun-Dong Wu,
Published: 27 October 2017
Abstract:
Bromodomains are epigenetic readers of acetylated lysines that are integral parts of histone tails. The 61 bromodomains in humans are structurally highly conserved but specifically bind to widely varying recognition motifs, suggesting that dynamic rather than static factors are responsible for recognition selectivity. To test this hypothesis, the dynamics of the binding sites and structural water molecules of four bromodomains (ATAD2, BAZ2B, BRD2(1) and CREBBP) representing four different subtypes is studied with 1 μs MD simulations using the RSFF2 force field. The different dynamics of the ZA-loops and BC-loops between the four bromodomains leads to distinct patterns for the opening and closing of the binding pocket. This in turn determines the structural and energetic properties of the structural waters in the binding pocket, suggesting that these waters are not only important for the recognition itself, as has been proposed previously, but also contribute to the selectivity of different bromodomains.
Naoki Miura, Kazuko Omodaka, Koudai Kimura, Akiko Matsumoto, Tsutomu Kikawa, Seri Takahashi, Naoko Takada, Hidetoshi Takahashi, , Masahiro Akiba, et al.
Published: 27 October 2017
Abstract:
The assessment of retinal nerve fiber layer defects (RNFLDs) is a useful part of glaucoma care. Here, we obtained en-face images of retinal layers below the inner limiting membrane (ILM) with swept source-optical coherence tomography (SS-OCT), and measured RNFLD angle with new software. This study included 105 eyes of 105 normal tension glaucoma (NTG) patients (age, 59.8 ± 13.2). Exclusion criteria were best-corrected visual acuity < 0.5, axial length > 28 mm, non-glaucoma ocular disease, and systemic disease affecting the visual field. We obtained 12 x 9 mm 3D volume scans centered on the macula with SS-OCT (DRI OCT-1, Topcon), and from these scans, created 3 averaged en-face images, each comprising 7 horizontal en-face images (total thickness: 18.2 μm). We labeled these averaged images, according to their depth below the ILM, as en-face images 1 (shallowest), 2 (middle) and 3 (deepest). In each image, a circle was drawn centered on the disc, with a radius of half the distance between the centers of the disc and macula. The investigator marked points where the edge of the RNFLD intersected this circle, and RNFLD angle (RNFLDA) was calculated with new software. Finally, we analyzed the association between RNFLDA, cpRNFLT, weighted RGC count (wrgc) and Humphrey field analyzer (HFA)-measured mean deviation (MD) and hemifield total deviation (TD), both overall and in each hemifield. En-face image 2 had the highest interclass reproducibility for measuring RNFLDA (intra-rater intraclass correlation coefficient (ICC): 0.988, inter-rater ICC: 0.962). The correlation coefficients with RNFLDA were: HFA MD, -0.60; superior TD, -0.73; inferior TD, -0.69; overall cpRNFLT, -0.27; superior hemifield cpRNFLT, -0.39; and inferior hemifield cpRNFLT, -0.53 (all p<0.001). RNFLDA measured in SS-OCT images had high reproducibility and was correlated to glaucoma severity. Our new method may be a valuable future part of glaucoma care.
Elvis Ofon, Harry Noyes, , , Martin Simuunza, Vincent Ebo’O, Flobert Njiokou, Mathurin Koffi, Bruno Bucheton, Pythagore Fogue, et al.
PLOS Neglected Tropical Diseases, Volume 11; https://doi.org/10.1371/journal.pntd.0005979

Abstract:
Human African Trypanosomiasis (HAT) is a neglected disease targeted for elimination as a public health problem by 2020. Elimination requires a better understanding of the epidemiology and clinical evolution of HAT. In addition to the classical clinical evolution of HAT, asymptomatic carriers and spontaneous cure have been reported in West Africa. A genetic component to human susceptibility to HAT has been suggested to explain these newly observed responses to infection. In order to test for genetic associations with infection response, genetic polymorphism in 17 genes were tested (APOL1, IL1B, IL4, IL4R, IL6, IL8, IL12B, IL12RB1, IL10, TNFA, INFG, MIF, HLA-G, HLA-A, HP, HPR and CFH). A case-control study was performed on 180 blood samples collected from 56 cases and 124 controls from Cameroon. DNA was extracted from blood samples. After quality control, 25 samples (24 controls and 1 case) were eliminated. The genotyping undertaken on 155 individuals including 55 cases and 100 controls were investigated at 96 loci (88 SNPs and 8 indels) located on 17 genes. Associations between these loci and HAT were estimated via a case-control association test. Analyses of 64 SNPs and 4 indels out of 96 identified in the selected genes reveal that the minor allele (T) of rs8062041 in haptoglobin (HP) appeared to be protective against HAT (p = 0.0002395, OR 0.359 (CI95 [0.204–0.6319])); indicating higher frequency in cases compared to controls. This minor allele with adjusted p value of 0.0163 is associated with a lower risk (protective effect) of developing sleeping sickness. The haptoglobin related protein HPR and HP are tightly linked and both are duplicated in some people and may lead to higher activity. This increased production could be responsible of the protection associated with rs8062041 even though this SNP is within HP. Human African trypanosomiasis (HAT) or sleeping sickness is a neglected tropical disease targeted for elimination by 2020. This elimination requires a better understanding of the epidemiology and clinical evolution of this disease. Beside the classical clinical evolution, asymptomatic carriers, seropositive and spontaneous cure of infected persons have been reported in West Africa. Arguments in favor of human genetic susceptibility to HAT have been raised to explain this variability in clinical presentation. This study investigated the genetic polymorphism of 17 genes between controls and sleeping sickness patients in Southern Cameroon in order to improve our knowledge of human susceptibility to trypanosome infections. We identified single nucleotide polymorphisms and indels in 17 selected genes involved in immune responses and carried out a case-control candidate gene association study and demonstrated differences between variants associated with the disease. From these genes, only haptoglobin (HP) at the SNP rs8062041 was found to have polymorphisms which were strongly associated with trypanosomiasis. The minor allele (T) at this SNP position appeared to be protective against HAT (p = 0.0002395, OR 0.359 (CI95 [0.204–0.6319])) reducing the risk of developing disease approximately threefold. The haptoglobin related protein (HPR) is adjacent to HP and is a component of the Trypanolytic factor that kills trypanosomes. The HP and HPR locus is duplicated in some people. The rs8062041 variant may be associated with this duplication and it is possible that increased production of HPR is the cause of the protection associated with rs8062041. The results reported here will contribute to the knowledge of the role of human genetics in disease progression, and thus lead to the identification of novel biomarkers which could involve development of new diagnostics, treatments and intervention strategies.
Jian Li, Zhen-Yu Yao, Chang She, Bin Ten, Chang Liu, Shu-Bin Lin, Qi-Rong Dong,
Published: 27 October 2017
Abstract:
Low-dose irradiation (LDI) has been used in clinics to treat human diseases, including chronic inflammation. This study assessed the effects of LDI on the inflammatory response of activated mouse primary peritoneal macrophages, and the underlying signal pathways. Primary peritoneal macrophages were isolated from mice and then incubated with lipopolysaccharide (LPS)-coated Ti microparticles (Ti-positive control) with or without brief exposure to LDI (X-ray, 0.5 Gy) 1 h later (Ti-LDI group) or left untreated in culture medium (Ti-negative control). The macrophages were then subjected to qRT-PCR, Western blot, cell viability CCK-8 assay, and ELISA. qRT-PCR analysis revealed the Ti-LDI group expressed significantly lower levels of IL-1β, IL-6, and TNF-α mRNA than those of the Ti-positive control group, while the ELISA data showed that Ti-LDI group had significantly lower secretion of IL-1β, IL-6, and TNF-α proteins. The most significant reduction associated with LDI was the secretion TNF-α protein, which barely increased from 13 to 25 h after treatment. Western blot data demonstrated that phosphorylation of p65 and ERK was much lower in the Ti-LDI group than in the controls. The data from the current study suggests that LDI of activated mouse macrophages was associated with significantly lower inflammation responses, compared with non-exposed activated macrophages, which was possibly through inhibition of the NF-κB and ERK pathways.
, , Muhammad Khalid Bashir, ,
Published: 27 October 2017
Abstract:
In most of the developing countries, lack of resources and little market accessibility are among the major factors that affect small farming household food security. This study aims to investigate the status of small farming households’ food security, and its determinants including the role of market accessibility factors in enhancing food security at household level. In addition, this study also determines the households’ perception about different kinds of livelihoods risks. This study is based on a household survey of 576 households conducted through face-to-face interviews using structured interviews in Punjab, Pakistan. Food security status is calculated using dietary intake method. The study findings show that one-fourth of the households are food insecure. The study findings reveal that farm households perceive increase in food prices, crop diseases, lack of irrigation water and increase in health expenses as major livelihood risks. Further, the results of logistic regression show that family size, monthly income, food prices, health expenses and debt are main factors influencing the food security status of rural households. Furthermore, the market accessibility factors (road distance and transportation cost) do significantly affect the small farming household food security. The results suggest that local food security can be enhanced by creating off-farm employment opportunities, improved transportation facilities and road infrastructure.
, Mavuto Mukaka, Brigitte Denis, Veronica S. Mlozowa, Malango Msukwa, Khumbo Kasambala, Mulinda Nyrienda, Theresa J. Allain, Brian Faragher, , et al.
Published: 27 October 2017
Abstract:
Mortality from acute bacterial meningitis (ABM) in sub-Saharan African adults and adolescents exceeds 50%. We tested if Goal Directed Therapy (GDT) was feasible for adults and adolescents with clinically suspected ABM in Malawi. Sequential patient cohorts of adults and adolescents with clinically suspected ABM were recruited in the emergency department of a teaching hospital in Malawi using a before/after design. Routine care was monitored in year one (P1). In year two (P2), nurses delivered protocolised GDT (rapid antibiotics, airway support, oxygenation, seizure control and fluid resuscitation) to a second cohort. The primary endpoint was composite mean number of clinical goals attained. Secondary endpoints were individual goals attained and death or disability from proven or probable ABM at day 40. 563 patients with suspected ABM were enrolled in the study; 273 were monitored in P1; 290 patients with suspected ABM received GDT in P2. 61% were male, median age 33 years and 90% were HIV co-infected. ABM was proven or probable in 132 (23%) patients. GDT attained more clinical goals compared to routine care: composite mean number of goals in P1 was 0·55 vs. 1·57 in P2 GDT (p<0·001); Death or disability by day 40 from proven or probable ABM occurred in 29/57 (51%) in P1 and 38/60 (63%) in P2 (p = 0·19). Nurse-led GDT in a resource-constrained setting was associated with improved delivery of protocolised care. Outcome was unaffected. www.isrctn.com ISRCTN96218197
, Jinha Park,
Published: 27 October 2017
Abstract:
The Hopfield model is a pioneering neural network model with associative memory retrieval. The analytical solution of the model in mean field limit revealed that memories can be retrieved without any error up to a finite storage capacity of O(N), where N is the system size. Beyond the threshold, they are completely lost. Since the introduction of the Hopfield model, the theory of neural networks has been further developed toward realistic neural networks using analog neurons, spiking neurons, etc. Nevertheless, those advances are based on fully connected networks, which are inconsistent with recent experimental discovery that the number of connections of each neuron seems to be heterogeneous, following a heavy-tailed distribution. Motivated by this observation, we consider the Hopfield model on scale-free networks and obtain a different pattern of associative memory retrieval from that obtained on the fully connected network: the storage capacity becomes tremendously enhanced but with some error in the memory retrieval, which appears as the heterogeneity of the connections is increased. Moreover, the error rates are also obtained on several real neural networks and are indeed similar to that on scale-free model networks.
, Xiao-Qing Sun, Rui Zhu, Ming Li, Wang Miao
Published: 27 October 2017
Abstract:
Emergency rescue material reserves are vital for the success of emergency rescue activities. In this study, we consider a situation where a government owned distribution center and framework agreement suppliers jointly store emergency rescue materials. Using a scenario-based approach to represent demand uncertainty, we propose a comprehensive transportation pattern for the following supply chain: “suppliers—government distribution center—disaster area.” Using a joint reserves model that includes the government and framework agreement suppliers, we develop a non-linear mathematic model that determines the choices of the framework suppliers, the corresponding optimal commitment quantities, and the quantity of materials that are stored at a government distribution center. Finally, we use IBM ILOG CPLEX to solve the numerical examples to verify the effectiveness of the mode and perform sensitivity analyses on the relevant parameters.
Michael Burnim, Julianne A. Ivy,
PLoS Neglected Tropical Diseases, Volume 11; https://doi.org/10.1371/journal.pntd.0006043

Abstract:
The mainstay of current schistosomiasis control programs is mass preventive chemotherapy of school-aged children with praziquantel. This treatment is delivered through school-based, community-based, or combined school- and community-based systems. Attaining very high coverage rates for children is essential in mass schistosomiasis treatment programs, as is ensuring that there are no persistently untreated subpopulations, a potential challenge for school-based programs in areas with low school enrollment. This review sought to compare the different treatment delivery methods based both on their coverage of school-aged children overall and on their coverage specifically of non-enrolled children. In addition, qualitative community or programmatic factors associated with high or low coverage rates were identified, with suggestions for overall coverage improvement. This review was registered prospectively with PROSPERO (CRD 42015017656). Five hundred forty-nine publication of potential relevance were identified through database searches, reference lists, and personal communications. Eligible studies included those published before October 2015, written in English or French, containing quantitative or qualitative data about coverage rates for MDA of school-aged children with praziquantel. Among the 22 selected studies, combined community- and school-based programs achieved the highest median coverage rates (89%), followed by community-based programs (72%). School-based programs had both the lowest median coverage of children overall (49%) and the lowest coverage of the non-enrolled subpopulation of children. Qualitatively, major factors affecting program success included fear of side effects, inadequate education about schistosomiasis, lack of incentives for drug distributors, and inequitable distribution to minority groups. This review provides an evidence-based framework for the development of future schistosomiasis control programs. Based on our results, a combined community and school-based delivery system should maximize coverage for both in- and out-of-school children, especially when combined with interventions such as snacks for treated children, educational campaigns, incentives for drug distributors, and active inclusion of marginalized groups. ClinicalTrials.gov CRD42015017656 Schistosomiasis is a chronic inflammatory condition, caused by parasitic flukes, that affects over 290 million people worldwide. Consequences of infection include anemia, stunted growth, liver abnormalities, and subfertility. Currently, the main approach to schistosomiasis control involves mass preventive treatment of school-aged children in endemic areas. The treatment, praziquantel, can be distributed through school-based, community-based, or combined school- and community-based systems. The first part of this systematic review compared the three delivery modes and found that combined delivery resulted in the best overall coverage of school-aged children, with community-only delivery the next-best approach. School-only delivery not only had the lowest overall coverage, but especially fell behind in targeting children not enrolled in school. As a whole, these results support the more frequent use of a combined approach to delivery in order to achieve the highest coverage rates and ensure that out-of-school children are not left persistently untreated. In the second part of this review the qualitative factors affecting program success were examined. The results indicate that overall treatment coverage can be improved via small interventions, such as snacks for participating children to reduce drug side effects, educational campaigns about schistosomiasis, incentives for drug distributors, and active inclusion of marginalized groups.
, , Eva Christalle, Holger Schulz, Birgit Watzke, , Lutz Götzmann, Harald Bailer, Sabine Zahn, Hanne Melchior
Published: 27 October 2017
Abstract:
Patients with depression often have limited access to outpatient psychotherapy following inpatient treatment. The objective of the study was to evaluate the long-term effectiveness of a telephone-based aftercare case management (ACM) intervention for patients with depression. We performed a prospective randomized controlled trial in four psychotherapeutic inpatient care units with N = 199 patients with major depression or dysthymia (F32.x, F33.x, F34.1, according to the ICD-10). The ACM consisted of six phone contacts at two-week intervals performed by trained and certified psychotherapists. The control group received usual care (UC). The primary outcome was depressive symptom severity (BDI-II) at 9-month follow-up, and secondary outcomes were health-related quality of life (SF-8, EQ-5D), self-efficacy (SWE), and the proportion of patients initiating outpatient psychotherapy. Mixed model analyses were conducted to compare improvements between treatment groups. Regarding the primary outcome of symptom severity, the groups did not significantly differ after 3 months (p = .132; ES = -0.23) or at the 9-month follow-up (p = .284; ES = -0.20). No significant differences in health-related quality of life or self-efficacy were found between groups. Patients receiving ACM were more likely to be in outpatient psychotherapy after 3 months (OR: 3.00[1.12–8.07]; p = .029) and 9 months (OR: 4.78 [1.55–14.74]; p = .006) than those receiving UC. Although telephone-based ACM did not significantly improve symptom severity, it seems to be a valuable approach for overcoming treatment barriers to the clinical pathways of patients with depression regarding their access to outpatient psychotherapy.
Marie Hagbom, , Malin Ekström, Younis Khalid, Maria Andersson, Magnus Lindh, Johan Nordgren,
Published: 27 October 2017
Abstract:
Rotavirus and norovirus cause acute gastroenteritis with severe diarrhoea and vomiting, symptoms that may lead to severe dehydration and death. The objective of this randomized double-blinded placebo-controlled study was to investigate whether ondansetron, a serotonin receptor antagonist could attenuate rotavirus- and norovirus-induced vomiting and diarrhoea, which would facilitate oral rehydration and possibly accelerate recovery and reduce need for hospitalization. Children with acute gastroenteritis, aged 6 months to 16 years where enrolled (n = 104) and randomized to one single oral dose (0.15mg/kg) of ondansetron (n = 52) or placebo (n = 52). The number of diarrhoea and vomiting episodes during the 24 hours following treatment was reported as well as the number of days with symptoms. Pathogens in faeces were diagnosed by real-time PCR. Outcome parameters were analyzed for rotavirus- and norovirus-positive children. One dose of oral ondansetron reduced duration of rotavirus clinical symptoms (p = 0.014), with a median of two days. Furthermore, ondansetron reduced diarrhea episodes, most pronounced in children that had been sick for more than 3 days before treatment (p = 0.028). Ondansetron may be a beneficial treatment for children with rotavirus gastroenteritis. European Clinical Trial Database EudraCT 2011-005700-15.
, Jaimie Poon, Michael W. Weiss
Published: 27 October 2017
Abstract:
After only two exposures to previously unfamiliar melodies, adults remember the tunes for over a week and the key for over a day. Here, we examined the development of long-term memory for melody and key. Listeners in three age groups (7- to 8-year-olds, 9- to 11-year-olds, and adults) heard two presentations of each of 12 unfamiliar melodies. After a 10-min delay, they heard the same 12 old melodies intermixed with 12 new melodies. Half of the old melodies were transposed up or down by six semitones from initial exposure. Listeners rated how well they recognized the melodies from the exposure phase. Recognition was better for old than for new melodies, for adults compared to children, and for older compared to younger children. Recognition ratings were also higher for old melodies presented in the same key at test as exposure, and the detrimental effect of the transposition affected all age groups similarly. Although memory for melody improves with age and exposure to music, implicit memory for key appears to be adult-like by 7 years of age.
, Marco Calabrò, Ricard Garcia-Serna, Carmen Ferrajolo, Concetta Crisafulli, ,
Published: 27 October 2017
Abstract:
Antipsychotic (AP) safety has been widely investigated. However, mechanisms underlying AP-associated pneumonia are not well-defined. The aim of this study was to investigate the known mechanisms of AP-associated pneumonia through a systematic literature review, confirm these mechanisms using an independent data source on drug targets and attempt to identify novel AP drug targets potentially linked to pneumonia. A search was conducted in Medline and Web of Science to identify studies exploring the association between pneumonia and antipsychotic use, from which information on hypothesized mechanism of action was extracted. All studies had to be in English and had to concern AP use as an intervention in persons of any age and for any indication, provided that the outcome was pneumonia. Information on the study design, population, exposure, outcome, risk estimate and mechanism of action was tabulated. Public repositories of pharmacology and drug safety data were used to identify the receptor binding profile and AP safety events. Cytoscape was then used to map biological pathways that could link AP targets and off-targets to pneumonia. The literature search yielded 200 articles; 41 were included in the review. Thirty studies reported a hypothesized mechanism of action, most commonly activation/inhibition of cholinergic, histaminergic and dopaminergic receptors. In vitro pharmacology data confirmed receptor affinities identified in the literature review. Two targets, thromboxane A2 receptor (TBXA2R) and platelet activating factor receptor (PTAFR) were found to be novel AP target receptors potentially associated with pneumonia. Biological pathways constructed using Cytoscape identified plausible biological links potentially leading to pneumonia downstream of TBXA2R and PTAFR. Innovative approaches for biological substantiation of drug-adverse event associations may strengthen evidence on drug safety profiles and help to tailor pharmacological therapies to patient risk factors.
, Allen R. Kunselman, Christy M. Stetter, Sadeer B. Hannush, Benjamin W. Roberts
Published: 27 October 2017
Abstract:
To review the graft survival rate, visual outcomes, and patient demographics of primary penetrating keratoplasty performed at Tenwek Hospital, a mission hospital in rural Kenya. A retrospective review was performed of the clinical records of patients who underwent primary penetrating keratoplasty for optical purposes from January 2012 to October 2014. The graft survival rates were constructed using the Kaplan-Meier method, and the effect of clinical and socioeconomic characteristics on time to graft failure were examined using Cox regression models. 118 patients met the inclusion criteria. The most common indication for surgery was keratoconus (66.1%), followed by corneal scar (22.0%). Despite all patients giving a verbal commitment to do so, 40 patients (33.9%) failed to make it to followup one year postoperatively. Graft survival at one year, inclusive of all indications, was 85.8%. Of the different indications, keratoconus had the highest one-year graft survival rate of 89.9%. Compared to the preoperative uncorrected visual acuity, 85.3% achieved an improvement at one year. Compared to patients who had completed college or university, the risk of developing graft failure was 4.7 times higher among patients with less education (P = 0.01). Corneal transplantation at Tenwek Hospital can be performed with a reasonable chance of success at one year, particularly in cases of keratoconus and in patients with higher educational backgrounds. Adherence to followup recommendations proves to be a challenge in this patient population. Additional studies of larger patient populations with longer follow up periods in similar settings may be helpful in informing appropriate patient selection and maximizing successful outcomes of corneal transplantation in low-resource settings.
, Tomoe Shimada, Yukiya Motomura,
Published: 27 October 2017
Abstract:
Transcription factors control many processes in plants and have high potentials to manipulate specialized metabolic pathways. Transcriptional regulation of the biosynthesis of monoterpenoid indole alkaloids (MIAs), nicotine alkaloids, and benzylisoquinoline alkaloids (BIAs) has been characterized using Catharanthus roseus, Nicotiana and Coptis plants. However, metabolic engineering in which specific transcription factors are used in alkaloid biosynthesis is limited. In this study, we characterized the effects of ectopic expression of CjWRKY1, which is a transcriptional activator with many targets in BIA biosynthesis in Coptis japonica (Ranunculaceae) and Eschscholzia californica (California poppy, Papaveraceae). Heterologous expression of CjWRKY1 in cultured California poppy cells induced increases in transcripts of several genes encoding BIA biosynthetic enzymes. Metabolite analyses indicated that the overexpression of the CjWRKY1 gene also induced increases in the accumulation of BIAs such as sanguinarine, chelerythrine, chelirubine, protopine, allocryptopine, and 10-hydroxychelerythrine in the culture medium. Previous characterization of EcbHLH1 and current results indicated that both transcription factors, WRKY1 and bHLH1, are substantially involved in the regulation of BIA biosynthesis. We discuss the function of CjWRKY1 in E. californica cells and its potential for metabolic engineering in BIA biosynthesis.
, , , Gabor Holló, Luciano Quaranta, Luca Agnifili, , Sara Giammaria, Davide Rastelli,
Published: 27 October 2017
Abstract:
To compare the detection rate of central visual field defect (CVFD) between the 30-degree Octopus G1 program (Dynamic strategy) and the HFA 10–2 SITA-Standard test in early glaucoma eyes not showing any CVFD on the HFA 24–2 SITA-Standard test. One eye of 41 early glaucoma patients without CVFD in the central 10° on HFA 24–2 test was tested with both the HFA 10–2 test and the Octopus G1 program 15 minutes apart, in random order. The primary outcome measure was the comparison of CVFD detection rates. Secondary outcome measures comprised the agreement in detecting CVFD, and the comparison of test durations and the numbers of depressed test points outside the central 10-degree area between the HFA 24–2 test and the Octopus G1 program. The mean age of the population was 65.2±10.1 years, and the mean deviation with HFA 24–2 was -3.26±2.6 dB. The mean test duration was not significantly different between the tests (p = 0.13). A CVFD was present in 33 (80.4%) HFA 10–2 test and in 23 (56.0%) Octopus G1 tests (p = 0.002). The overall agreement between the HFA 10–2 and Octopus G1 examinations in classifying eyes as having or not having CVFD was moderate (Cohen’s kappa 0.47). The Octopus G1 program showed 69.6% sensitivity and 100% specificity to detect CVFD in eyes where the HFA 10–2 test revealed a CVFD. The number of depressed test points (p<5%) outside the central 10° area detected with the Octopus G1 program (19.68±10.6) was significantly higher than that detected with the HFA 24–2 program (11.95±5.5, p<0.001). Both HFA 10–2 and Octopus G1programs showed CVFD not present at HFA 24–2 test although the agreement was moderate. The use of a single Octopus G1 examination may represent a practical compromise for the assessment of both central and peripheral visual field up to 30° eccentricity without any additional testing and increasing the total investigation time.
, Erin B. Palmisano, Emily Dansereau, Alexandra Schaefer, Alexander Woldeab, , Benito Salvatierra, Bernardo Hernandez-Prado, Ali H. Mokdad
Published: 27 October 2017
Abstract:
The Salud Mesoamérica Initiative (SMI) is a three-operation strategy, and is a pioneer in the world of results-based aid (RBA) in terms of the success it has achieved in improving health system inputs following its initial operation. This success in meeting pre-defined targets is rare in the world of financial assistance for health. We investigated the influential aspects of SMI that could have contributed to its effectiveness in improving health systems, with the aim of providing international donors, bilateral organizations, philanthropies, and recipient countries with new perspectives that can help increase the effectiveness of future assistance for health, specifically in the arena of RBA. Qualitative methods based on the criteria of relevance and effectiveness proposed by the Development Assistance Committee of the Organization for Economic Co-operation and Development. Our methods included document review, key informant interviews, a focus group discussion, and a partnership analysis. A purposive sample of 113 key informants, comprising donors, representatives from the Inter-American Development Bank, ministries of health, technical assistance organizations, evaluation organizations, and health care providers. During May–October 2016, we interviewed regarding the relevance and effectiveness of SMI. Themes emerged relative to the topics we investigated, and covered the design and the drivers of success of the initiative. The success is due to 1) the initiative’s regional approach, which pressured recipient countries to compete toward meeting targets, 2) a robust and flexible design that incorporated the richness of input from stakeholders at all levels, 3) the design-embedded evaluation component that created a culture of accountability among recipient countries, and 4) the reflective knowledge environment that created a culture of evidence-based decision-making. A regional approach involving all appropriate stakeholders, and based on knowledge sharing and embedded evaluation can help ensure the effectiveness of future results-based aid programs for health in global settings.
, Danna Liu, Hongyan Cheng, Dai Qionglin, Junzhong Yang
Published: 27 October 2017
Abstract:
Chimera states, which consist of coexisting domains of spatially coherent and incoherent dynamics, have been intensively investigated in the past decade. In this work, we report a special chimera state, 2-frequency chimera state, in one-dimensional ring of nonlocally coupled Brusselators. In a 2-frequency chimera state, there exist two types of coherent domains and oscillators in different types of coherent domains have different mean phase velocities. We present the stability diagram of 2-frequency chimera state and study the transition between the 2-frequency chimera state and an ordinary 2-cluster chimera state.
Behnoushsadat Ghodsalavi, Nanna Bygvraa Svenningsen, Xiuli Hao, , , , , Ole Nybroe
Published: 27 October 2017
Abstract:
It is important to identify and recover bacteria associating with fungi under natural soil conditions to enable eco-physiological studies, and to facilitate the use of bacterial-fungal consortia in environmental biotechnology. We have developed a novel type of baiting microcosm, where fungal hyphae interact with bacteria under close-to-natural soil conditions; an advantage compared to model systems that determine fungal influences on bacterial communities in laboratory media. In the current approach, the hyphae are placed on a solid support, which enables the recovery of hyphae with associated bacteria in contrast to model systems that compare bulk soil and mycosphere soil. We used the baiting microcosm approach to determine, for the first time, the composition of the bacterial community associating in the soil with hyphae of the phosphate-solubilizer, Penicillium bilaii. By applying a cultivation-independent 16S rRNA gene-targeted amplicon sequencing approach, we found a hypha-associated bacterial community with low diversity compared to the bulk soil community and exhibiting massive dominance of Burkholderia OTUs. Burkholderia is known be abundant in soil environments affected by fungi, but the discovery of this massive dominance among bacteria firmly associating with hyphae in soil is novel and made possible by the current bait approach.
, Lishuai Liu, Xuemin Ye
Published: 27 October 2017
Abstract:
The stability of magnetohydrodynamic flow in a duct with perfectly conducting walls is investigated in the presence of a homogeneous and constant static magnetic field. The temporal growth and spatial distribution of perturbations are obtained by solving iteratively the direct and adjoint governing equations with respect of perturbations, based on nonmodal stability theory. The effect of the applied magnetic field, as well as the aspect ratio of the duct on the stability of the magnetohydrodynamic duct flow is taken into account. The computational results show that, weak jets appear near the sidewalls at a moderate magnetic field and the velocity of the jet increases with the increase of the intensity of the magnetic field. The duct flow is stable at either weak or strong magnetic field, but becomes unstable at moderate intensity magnetic field, and the stability is invariance with the aspect ratio of the duct. The instability of magnetohydrodynamic duct flow is related with the exponential growth of perturbations evolving on the fully developed jets. Transient growth of perturbations is also observed in the computation and the optimal perturbation is found to be in the form of streamwise vortices and localized within the sidewall layers. By contrast, the Hartmann layer perpendicular to the magnetic field is irrelevant to the stability issue of the magnetohydrodynamic duct flow.
, B. Silvano Zanutto
Published: 27 October 2017
Abstract:
Animals are proposed to learn the latent rules governing their environment in order to maximize their chances of survival. However, rules may change without notice, forcing animals to keep a memory of which one is currently at work. Rule switching can lead to situations in which the same stimulus/response pairing is positively and negatively rewarded in the long run, depending on variables that are not accessible to the animal. This fact raises questions on how neural systems are capable of reinforcement learning in environments where the reinforcement is inconsistent. Here we address this issue by asking about which aspects of connectivity, neural excitability and synaptic plasticity are key for a very general, stochastic spiking neural network model to solve a task in which rules change without being cued, taking the serial reversal task (SRT) as paradigm. Contrary to what could be expected, we found strong limitations for biologically plausible networks to solve the SRT. Especially, we proved that no network of neurons can learn a SRT if it is a single neural population that integrates stimuli information and at the same time is responsible of choosing the behavioural response. This limitation is independent of the number of neurons, neuronal dynamics or plasticity rules, and arises from the fact that plasticity is locally computed at each synapse, and that synaptic changes and neuronal activity are mutually dependent processes. We propose and characterize a spiking neural network model that solves the SRT, which relies on separating the functions of stimuli integration and response selection. The model suggests that experimental efforts to understand neural function should focus on the characterization of neural circuits according to their connectivity, neural dynamics, and the degree of modulation of synaptic plasticity with reward.
, Gróa Pétursdóttir, Hlynur Bárðarson, Ragnar Edvardsson
Published: 27 October 2017
Abstract:
Archaeological excavations of historical fishing sites across the North Atlantic have recovered high quantities of Atlantic cod (Gadus morhua) bones. In the current study we use Atlantic cod otoliths from archaeological excavations of a historical fishing sites in north-west Iceland, dated to AD 970 –AD 1910 to examine historical growth trajectories of cod. No large scale growth variations or shifts in growth patterns were observed in the current chronologies, supporting the stability of historical Atlantic cod growth trajectories. The most significant variation in growth patterns was consistent with those that have been observed in recent times, for example, reduced early juvenile growth during periods of colder ocean temperature. The current results represent a high resolution chronological record of north-east Atlantic cod growth, greatly increasing the prior temporal range of such data, thereby providing a valuable baseline for a broad range of studies on Atlantic cod growth.
Bo-I Chuang, , , , I-Ming Jou, Wei-Jr Lin,
Published: 27 October 2017
Abstract:
Trigger finger has become a prevalent disease that greatly affects occupational activity and daily life. Ultrasound imaging is commonly used for the clinical diagnosis of trigger finger severity. Due to image property variations, traditional methods cannot effectively segment the finger joint’s tendon structure. In this study, an adaptive texture-based active shape model method is used for segmenting the tendon and synovial sheath. Adapted weights are applied in the segmentation process to adjust the contribution of energy terms depending on image characteristics at different positions. The pathology is then determined according to the wavelet and co-occurrence texture features of the segmented tendon area. In the experiments, the segmentation results have fewer errors, with respect to the ground truth, than contours drawn by regular users. The mean values of the absolute segmentation difference of the tendon and synovial sheath are 3.14 and 4.54 pixels, respectively. The average accuracy of pathological determination is 87.14%. The segmentation results are all acceptable in data of both clear and fuzzy boundary cases in 74 images. And the symptom classifications of 42 cases are also a good reference for diagnosis according to the expert clinicians’ opinions.
Mukherjee Sunil Kumar, Bhaben Tanti, , Sunil Kumar Mukherjee,
Published: 27 October 2017
Abstract:
Cowpea is an important grain legume crop of Africa, Latin America, and Southeast Asia. Leaf curl and golden mosaic diseases caused by Mungbean yellow mosaic India virus (MYMIV) have emerged as most devastating viral diseases of cowpea in Southeast Asia. In this study, we employed RNA interference (RNAi) strategy to control cowpea-infecting MYMIV. For this, we generated transgenic cowpea plants harbouring three different intron hairpin RNAi constructs, containing the AC2, AC4 and fusion of AC2 and AC4 (AC2+AC4) of seven cowpea-infecting begomoviruses. The T0 and T1 transgenic cowpea lines of all the three constructs accumulated transgene-specific siRNAs. Transgenic plants were further assayed up to T1 generations, for resistance to MYMIV using agro-infectious clones. Nearly 100% resistance against MYMIV infection was observed in transgenic lines, expressing AC2-hp and AC2+AC4-hp RNA, when compared with untransformed controls and plants transformed with empty vectors, which developed severe viral disease symptoms within 3 weeks. The AC4-hp RNA expressing lines displayed appearance of milder symptoms after 5 weeks of MYMIV-inoculation. Northern blots revealed a positive correlation between the level of transgene-specific siRNAs accumulation and virus resistance. The MYMIV-resistant transgenic lines accumulated nearly zero or very low titres of viral DNA. The transgenic cowpea plants had normal phenotype with no yield penalty in greenhouse conditions. This is the first demonstration of RNAi-derived resistance to MYMIV in cowpea.
, Corina E. Van Middelaar, Pim F. Mostert, Ariëtte T. M. Van Knegsel, Bas Kemp, ,
Published: 27 October 2017
Abstract:
Shortening or omitting the dry period of dairy cows improves metabolic health in early lactation and reduces management transitions for dairy cows. The success of implementation of these strategies depends on their impact on milk yield and farm profitability. Insight in these impacts is valuable for informed decision-making by farmers. The aim of this study was to investigate how shortening or omitting the dry period of dairy cows affects production and cash flows at the herd level, and greenhouse gas emissions per unit of milk, using a dynamic stochastic simulation model. The effects of dry period length on milk yield and calving interval assumed in this model were derived from actual performance of commercial dairy cows over multiple lactations. The model simulated lactations, and calving and culling events of individual cows for herds of 100 cows. Herds were simulated for 5 years with a dry period of 56 (conventional), 28 or 0 days (n = 50 herds each). Partial cash flows were computed from revenues from sold milk, calves, and culled cows, and costs from feed and rearing youngstock. Greenhouse gas emissions were computed using a life cycle approach. A dry period of 28 days reduced milk production of the herd by 3.0% in years 2 through 5, compared with a dry period of 56 days. A dry period of 0 days reduced milk production by 3.5% in years 3 through 5, after a dip in milk production of 6.9% in year 2. On average, dry periods of 28 and 0 days reduced partial cash flows by €1,249 and €1,632 per herd per year, and increased greenhouse gas emissions by 0.7% and 0.5%, respectively. Considering the potential for enhancing cow welfare, these negative impacts of shortening or omitting the dry period seem justifiable, and they might even be offset by improved health.
Published: 27 October 2017
Abstract:
Convergent evolution in organismal function can arise from nonconvergent changes in traits that contribute to that function. Theory predicts that low resource availability and high maintenance costs in extreme environments select for reductions in organismal energy demands, which could be attained through modifications of body size or metabolic rate. We tested for convergence in energy demands and underlying traits by investigating livebearing fish (genus Poecilia) that have repeatedly colonized toxic, hydrogen sulphide-rich springs. We quantified variation in body size and routine metabolism across replicated sulphidic and non-sulphidic populations in nature, modelled total organismal energy demands, and conducted a common-garden experiment to test whether population differences had a genetic basis. Sulphidic populations generally exhibited smaller body sizes and lower routine metabolic rates compared to non-sulphidic populations, which together caused significant reductions in total organismal energy demands in extremophile populations. Although both mechanisms contributed to variation in organismal energy demands, variance partitioning indicated reductions of body size overall had a greater effect than reductions of routine metabolism. Finally, population differences in routine metabolism documented in natural populations were maintained in common-garden reared individuals, indicating evolved differences. In combination with other studies, these results suggest that reductions in energy demands may represent a common theme in adaptation to physiochemical stressors. Selection for reduced energy demand may particularly affect body size, which has implications for life history evolution in extreme environments.
PLOS Neglected Tropical Diseases, Volume 11; https://doi.org/10.1371/journal.pntd.0006026

Abstract:
Leishmania is a protozoan parasite that alternates its life cycle between the sand-fly vector and the mammalian host. This alternation involves environmental changes and leads the parasite to dynamic modifications in morphology, metabolism, cellular signaling and regulation of gene expression to allow for a rapid adaptation to new conditions. The L-arginine pathway in L. amazonensis is important during the parasite life cycle and interferes in the establishment and maintenance of the infection in mammalian macrophages. Host arginase is an immune-regulatory enzyme that can reduce the production of nitric oxide by activated macrophages, directing the availability of L-arginine to the polyamine pathway, resulting in parasite replication. In this work, we performed transcriptional profiling to identify differentially expressed genes in L. amazonensis wild-type (La-WT) versus L. amazonensis arginase knockout (La-arg-) promastigotes and axenic amastigotes. A total of 8253 transcripts were identified in La-WT and La-arg- promastigotes and axenic amastigotes, about 60% of them codifying hypothetical proteins and 443 novel transcripts, which did not match any previously annotated genes. Our RNA-seq data revealed that 85% of genes were constitutively expressed. The comparison of transcriptome and metabolome data showed lower levels of arginase and higher levels of glutamate-5-kinase in La-WT axenic amastigotes compared to promastigotes. The absence of arginase activity in promastigotes increased the levels of pyrroline 5-carboxylate reductase, but decreased the levels of arginosuccinate synthase, pyrroline 5-carboxylate dehydrogenase, acetylornithine deacetylase and spermidine synthase transcripts levels. These observations can explain previous metabolomic data pointing to the increase of L-arginine, citrulline and L-glutamate and reduction of aspartate, proline, ornithine and putrescine. Altogether, these results indicate that arginase activity is important in Leishmania gene expression modulation during differentiation and adaptation to environmental changes. Here, we confirmed this hypothesis with the identification of differential gene expression of the enzymes involved in biosynthesis of amino acids, arginine and proline metabolism and arginine biosynthesis. All data provided information about the transcriptomic profiling and the expression levels of La-WT and La-arg- promastigotes and axenic amastigotes. These findings revealed the importance of arginase in parasite survival and differentiation, and indicated the existence of a coordinated response in the absence of arginase activity related to arginine and polyamine pathways. Leishmania are auxotrophic for many essential nutrients, including amino acids. In this way, the parasite needs to uptake the amino acids from the environment. The uptake of amino acids is mediated by amino acid transporters that are unique for Leishmania. As part of polyamine pathway, the arginase converts L-arginine to ornithine and furthermore to putrescine, products which are essential for parasite growth. On the other hand, the absence of arginase activity could alter the metabolism of the parasite to surpass the external signals during the life cycle and the fate of infection. The transcriptional profiling of La-WT and La-arg- promastigotes and axenic amastigotes revealed 8253 transcripts, 60% encoding hypothetical proteins and 443 novel transcripts. In addition, our data revealed that 85% of the genes were constitutively expressed. Among the 15% (1268 genes) of the differentially expressed genes, we identified genes up- and down-regulated comparing the transcript abundance from different life cycle stages of the parasite and in the presence or absence of arginase. We also combined the transcriptional with metabolic profile that revealed a proportional correlation between enzyme and metabolites in the polyamine pathway. The differentiation of promastigotes to amastigotes alters the expression of enzymes from polyamines biosynthesis, which modulates ornithine, L-glutamate, proline and putrescine levels. In addition, the absence of arginase activity increased the levels of L-arginine, citrulline and L-glutamate and decreased the levels of aspartate, proline, ornithine and putrescine in promastigotes by differential modulation of genes involved in its metabolism. Altogether these data provided additional insights into how Leishmania is able to modulate its biological functions in the presence or absence of arginase activity to survive during environmental changes.
, , , Ninna S. Hansen, Christa Broholm, , , Elisabeth R. Mathiesen, ,
Published: 27 October 2017
Abstract:
Fetal exposure to maternal diabetes increases the risk of type 2 diabetes (T2DM), possibly mediated by epigenetic mechanisms. Low blood TXNIP DNA methylation has been associated with elevated glucose levels and risk of T2DM, and increased skeletal muscle TXNIP gene expression was reported in subjects with impaired glucose metabolism or T2DM. Subcutaneous adipose tissue (SAT) and skeletal muscle play a key role in the control of whole body glucose metabolism and insulin action. The extent to which TXNIP DNA methylation levels are decreased and/or gene expression levels increased in SAT or skeletal muscle of a developmentally programmed at-risk population is unknown. The objective of this study was to investigate TXNIP DNA methylation and gene expression in SAT and skeletal muscle, and DNA methylation in blood, from adult offspring of women with gestational diabetes (O-GDM, n = 82) or type 1 diabetes (O-T1DM, n = 67) in pregnancy compared with offspring of women from the background population (O-BP, n = 57). SAT TXNIP DNA methylation was increased (p = 0.032) and gene expression decreased (p = 0.001) in O-GDM, but these differences were attenuated after adjustment for confounders. Neither blood/muscle TXNIP DNA methylation nor muscle gene expression differed between groups. We found no evidence of decreased TXNIP DNA methylation or increased gene expression in metabolic target tissues of offspring exposed to maternal diabetes. Further studies are needed to confirm and understand the paradoxical SAT TXNIP DNA methylation and gene expression changes in O-GDM subjects.
, , , Jai Deep Thakur, Rimal H. Dossani, Devi Prasad Patra, Kevin Phan, Hesam Akbarian-Tefaghi, Frank Farokhi, Christina Notarianni, et al.
Published: 27 October 2017
Abstract:
United States healthcare reforms are focused on curtailing rising expenditures. In neurosurgical domain, limited or no data exists identifying potential modifiable targets associated with high-hospitalization cost for cerebrovascular procedures such as extracranial-intracranial (ECIC) bypass. Our study objective was to develop a predictive model of initial cost for patients undergoing bypass surgery. In an observational cohort study, we analyzed patients registered in the Nationwide Inpatient Sample (2002–2011) that underwent ECIC bypass. Split-sample 1:1 randomization of the study cohort was performed. Hospital cost data was modelled using ordinary least square to identity potential drivers impacting initial hospitalization cost. Subsequently, a validated clinical app for estimated hospitalization cost is proposed (https://www.neurosurgerycost.com/calc/ec-ic-by-pass). Overall, 1533 patients [mean age: 45.18 ± 19.51 years; 58% female] underwent ECIC bypass for moyamoya disease [45.1%], cerebro-occlusive disease (COD) [23% without infarction; 12% with infarction], unruptured [12%] and ruptured [4%] aneurysms. Median hospitalization cost was $37,525 (IQR: $16,225-$58,825). Common drivers impacting cost include Asian race, private payer, elective admission, hyponatremia, neurological and respiratory complications, acute renal failure, bypass for moyamoya disease, COD without infarction, medium and high volume centers, hospitals located in Midwest, Northeast, and West region, total number of diagnosis and procedures, days to bypass and post-procedural LOS. Our model was validated in an independent cohort and using 1000-bootstrapped replacement samples. Identified drivers of hospital cost after ECIC bypass could potentially be used as an adjunct for creation of data driven policies, impact reimbursement criteria, aid in-hospital auditing, and in the cost containment debate.
, , Lee Smith, Benjamin Gardner, Davy Vancampfort
Published: 27 October 2017
Abstract:
Considering that physical activity is associated with healthy ageing and helps to delay, prevent, or manage a plethora of non-communicable diseases in older adults, there is a need to investigate the factors that influence physical activity participation in this population. Thus, we investigated physical activity correlates among community-dwelling older adults (aged ≥50 years) in six low- and middle-income countries. Cross-sectional data were analyzed from the World Health Organization’s Study on Global Ageing and Adult Health. Physical activity was assessed by the Global Physical Activity Questionnaire. Participants were dichotomized into low (i.e., not meeting 150 minutes of moderate physical activity per week) and moderate-to-high physically active groups. Associations between physical activity and a range of correlates were examined using multivariable logistic regressions. The overall prevalence (95%CI) of people not meeting recommended physical activity levels in 34,129 participants (mean age 62.4 years, 52.1% female) was 23.5% (22.3%-24.8%). In the multivariable analysis, older age and unemployment were significant sociodemographic correlates of low physical activity. Individuals with low body mass index (<18.5kg/m2), bodily pain, asthma, chronic back pain, chronic obstructive pulmonary disease, hearing problems, stroke, visual impairment, slow gait, and weak grip strength were less likely to meet physical activity targets in the overall sample (P<0.05). The associations varied widely between countries. Our data illustrates that a multitude of factors influence physical activity target achievement in older adults, which can inform future interventions across low- and middle-income countries to assist people of this age group to engage in regular physical activity. Future prospective cohort studies are also required to investigate the directionality and mediators of the relationships observed.
, Rebecca E. Ravenelle, Johanna J. Monro,
Published: 27 October 2017
Abstract:
White Nose Syndrome (WNS) greatly increases the over-winter mortality of little brown (Myotis lucifugus), Indiana (M. sodalis), northern (M. septentrionalis), and tricolored (Perimyotis subflavus) bats, and is caused by cutaneous infections with Pseudogymnoascus destructans (Pd). Big brown bats (Eptesicus fuscus) are highly resistant to Pd infections. Seven different fatty acids (myristic, pentadecanoic, palmitic, palmitoleic, oleic, and, linoleic acids) occur in the wing epidermis of both M. lucifugus and E. fuscus, 4 of which (myristic, palmitoleic, oleic, and, linoleic acids) inhibit Pd growth. The amounts of myristic and linoleic acids in the epidermis of M. lucifugus decrease during hibernation, thus we predicted that the epidermal fatty acid profile of M. lucifugus during hibernation has a reduced ability to inhibit Pd growth. Laboratory Pd growth experiments were conducted to test this hypothesis. The results demonstrated that the fatty acid profile of M. lucifugus wing epidermis during hibernation has a reduced ability to inhibit the growth of Pd. Additional Pd growth experiments revealed that: a) triacylglycerols composed of known anti-Pd fatty acids do not significantly affect growth, b) pentadecanoic acid inhibits Pd growth, and c) 1-oleoglycerol, which is found in the wing epidermis of E. fuscus, also inhibits the growth of this fungus. Analyses of white adipose from M. lucifugus also revealed the selective retention of oleic and linoleic acids in this tissue during hibernation.
Published: 27 October 2017
Abstract:
In principle, formal dynamical models of decision making hold the potential to represent fundamental computations underpinning value-based (i.e., preferential) decisions in addition to perceptual decisions. Sequential-sampling models such as the race model and the drift-diffusion model that are grounded in simplicity, analytical tractability, and optimality remain popular, but some of their more recent counterparts have instead been designed with an aim for more feasibility as architectures to be implemented by actual neural systems. Connectionist models are proposed herein at an intermediate level of analysis that bridges mental phenomena and underlying neurophysiological mechanisms. Several such models drawing elements from the established race, drift-diffusion, feedforward-inhibition, divisive-normalization, and competing-accumulator models were tested with respect to fitting empirical data from human participants making choices between foods on the basis of hedonic value rather than a traditional perceptual attribute. Even when considering performance at emulating behavior alone, more neurally plausible models were set apart from more normative race or drift-diffusion models both quantitatively and qualitatively despite remaining parsimonious. To best capture the paradigm, a novel six-parameter computational model was formulated with features including hierarchical levels of competition via mutual inhibition as well as a static approximation of attentional modulation, which promotes “winner-take-all” processing. Moreover, a meta-analysis encompassing several related experiments validated the robustness of model-predicted trends in humans’ value-based choices and concomitant reaction times. These findings have yet further implications for analysis of neurophysiological data in accordance with computational modeling, which is also discussed in this new light.
, , Shuai Zhang, Wenyu Zhang, Rongyu Liu
Published: 27 October 2017
Abstract:
The challenge of detecting research topics in a specific research field has attracted attention from researchers in the bibliometrics community. In this study, to solve two problems of clustering papers, i.e., the influence of different distributions of citation links and involved textual features on similarity computation, the authors propose a hybrid self-optimized clustering model to detect research topics by extending the hybrid clustering model to identify “core documents”. First, the Amsler network, consisting of bibliographic coupling and co-citation links, is created to calculate the citation-based similarity based on the cosine angle of papers. Second, the cosine similarity is also used to compute the text-based similarity, which consists of the textual statistical and topological features. Then, the cosine angle of the linear combination of citation- and text-based similarity is considered as the hybrid similarity. Finally, the Louvain method is applied to cluster papers, and the terms based on term frequency are used to label clusters. To test the performance of the proposed model, a dataset related to the data envelopment analysis field is used for comparison and analysis of clustering results. Based on the benchmark built, different clustering methods with different citation links or textual features are compared according to evaluation measures. The results show that the proposed model can obtain reasonable and effective clustering results, and the research topics of data envelopment analysis field are also analyzed based on the proposed model. As different features are considered in the proposed model compared with previous hybrid clustering models, the proposed clustering model can provide inspiration for further studies on topic identification by other researchers.
Daniel B. Kramer, Kara Stevens, Nicholas E. Williams, Seeta A. Sistla, , Gerald R. Urquhart
Published: 27 October 2017
Abstract:
Anthropogenic threats to natural systems can be exacerbated due to connectivity between marine, freshwater, and terrestrial ecosystems, complicating the already daunting task of governance across the land-sea interface. Globalization, including new access to markets, can change social-ecological, land-sea linkages via livelihood responses and adaptations by local people. As a first step in understanding these trans-ecosystem effects, we examined exit and entry decisions of artisanal fishers and smallholder farmers on the rapidly globalizing Caribbean coast of Nicaragua. We found that exit and entry decisions demonstrated clear temporal and spatial patterns and that these decisions differed by livelihood. In addition to household characteristics, livelihood exit and entry decisions were strongly affected by new access to regional and global markets. The natural resource implications of these livelihood decisions are potentially profound as they provide novel linkages and spatially-explicit feedbacks between terrestrial and marine ecosystems. Our findings support the need for more scientific inquiry in understanding trans-ecosystem tradeoffs due to linked-livelihood transitions as well as the need for a trans-ecosystem approach to natural resource management and development policy in rapidly changing coastal regions.
Kenta Furukawa, , Eiji Miyoshi, Hidetoshi Eguchi, Hiroaki Nagano, Katsuyoshi Matsunami, Satoshi Nagaoka, Daisaku Yamada, Tadafumi Asaoka, , et al.
Published: 27 October 2017
Abstract:
Single-agent immunotherapy is ineffective against poorly immunogenic cancers, including pancreatic ductal adenocarcinoma (PDAC). The aims of this study were to demonstrate the feasibility of production of novel autologous tumor lysate vaccines from resected PDAC tumors, and verify vaccine safety and efficacy. Fresh surgically resected tumors obtained from human patients were processed to enzymatically synthesize α-gal epitopes on the carbohydrate chains of membrane glycoproteins. Processed membranes were analyzed for the expression of α-gal epitopes and the binding of anti-Gal, and vaccine efficacy was assessed in vitro and in vivo. Effective synthesis of α-gal epitopes was demonstrated after processing of PDAC tumor lysates from 10 different patients, and tumor lysates readily bound an anti-Gal monoclonal antibody. α-gal(+) PDAC tumor lysate vaccines elicited strong antibody production against multiple tumor-associated antigens and activated multiple tumor-specific T cells. The lysate vaccines stimulated a robust immune response in animal models, resulting in tumor suppression and a significant improvement in survival without any adverse events. Our data suggest that α-gal(+) PDAC tumor lysate vaccination may be a practical and effective new immunotherapeutic approach for treating pancreatic cancer.
Argelia Figueroa, Reena K. Gulati, Jeanette J. Rainey
Published: 27 October 2017
Abstract:
Mass gatherings create environments conducive to the transmission of infectious diseases. Thousands of mass gatherings are held annually in the United States; however, information on the frequency and characteristics of respiratory disease outbreaks and on the use of nonpharmaceutical interventions at these gatherings is scarce. We administered an online assessment to the 50 state health departments and 31 large local health departments in the United States to gather information about mass gathering-related respiratory disease outbreaks occurring between 2009 and 2014. The assessment also captured information on the use of nonpharmaceutical interventions to slow disease transmission in these settings. We downloaded respondent data into a SAS dataset for descriptive analyses. We received responses from 43 (53%) of the 81 health jurisdictions. Among these, 8 reported 18 mass gathering outbreaks. More than half (n = 11) of the outbreaks involved zoonotic transmission of influenza A (H3N2v) at county and state fairs. Other outbreaks occurred at camps (influenza A (H1N1)pdm09 [n = 2] and A (H3) [n = 1]), religious gatherings (influenza A (H1N1)pdm09 [n = 1] and unspecified respiratory virus [n = 1]), at a conference (influenza A (H1N1)pdm09), and a sporting event (influenza A). Outbreaks ranged from 5 to 150 reported cases. Of the 43 respondents, 9 jurisdictions used nonpharmaceutical interventions to slow or prevent disease transmission. Although respiratory disease outbreaks with a large number of cases occur at many types of mass gatherings, our assessment suggests that such outbreaks may be uncommon, even during the 2009 influenza A (H1N1) pandemic, which partially explains the reported, but limited, use of nonpharmaceutical interventions. More research on the characteristics of mass gatherings with respiratory disease outbreaks and effectiveness of nonpharmaceutical interventions would likely be beneficial for decision makers at state and local health departments when responding to future outbreaks and pandemics.
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