AMRC Open Research

Journal Information
EISSN : 25176900
Current Publisher: F1000 Research Ltd (10.12688)
Total articles ≅ 14
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Latest articles in this journal

Published: 29 May 2020
AMRC Open Research; doi:10.12688/amrcopenres

Sophie R. Cook, Rafael A. Badell-Grau, Emily D. Kirkham, Kimberley M. Jones, Brendan P. Kelly, Jincy Winston, Helen Waller-Evans, Nicholas D. Allen, Emyr Lloyd-Evans
Published: 18 May 2020
AMRC Open Research, Volume 2; doi:10.12688/amrcopenres.12903.1

Abstract:
Good’s buffers are commonly used for cell culture and, although developed to have minimal to no biological impact, they cause alterations in cellular processes such as autophagy and lysosomal enzyme activity. Using Chinese hamster ovary cells and induced pluripotent stem cell-derived neurons, this study explores the effect of zwitterionic buffers, specifically HEPES, on lysosomal volume and Ca2+ levels. Certain zwitterionic buffers lead to lysosomal expansion and reduced lysosomal Ca2+. Care should be taken when selecting buffers for growth media to avoid detrimental impacts on lysosomal function.
Grant Mair, Francesca Chappell, Chloe Martin, David Dye, Philip M. Bath, Keith W. Muir, Rüdiger Von Kummer, Rustam Al-Shahi Salman, Peter A. G. Sandercock, Malcolm Robert MacLeod, et al.
Published: 28 April 2020
AMRC Open Research, Volume 2; doi:10.12688/amrcopenres.12904.1

Abstract:
Background: Artificial intelligence-based software may automatically detect ischaemic stroke lesions and provide an Alberta Stroke Program Early CT score (ASPECTS) on CT, and identify arterial occlusion and provide a collateral score on CTA. Large-scale independent testing will inform clinical use, but is lacking. We aim to test e-ASPECTS and e-CTA (Brainomix, Oxford UK) using CT scans obtained from a range of clinical studies. Methods: Using prospectively collected baseline CT and CTA scans from 10 national/international clinical stroke trials or registries (total >6600 patients), we will select a large clinically representative sample for testing e-ASPECTS and e-CTA compared to previously acquired independent expert human interpretation (reference standard). Our primary aims are to test agreement between software-derived and masked human expert ASPECTS, and the diagnostic accuracy of e-ASPECTS for identifying all causes of stroke symptoms using follow-up imaging and final clinical opinion as diagnostic ground truth. Our secondary aims are to test when and why e-ASPECTS is more or less accurate, or succeeds/fails to produce results, agreement between e-CTA and human expert CTA interpretation, and repeatability of e-ASPECTS/e-CTA results. All testing will be conducted on an intention-to-analyse basis. We will assess agreement between software and expert-human ratings and test the diagnostic accuracy of software. Conclusions: RITeS will provide comprehensive, robust and representative testing of e-ASPECTS and e-CTA against the current gold-standard, expert-human interpretation.
Rebecca Charlton, Catherine J Crompton, Amanda Roestorf, Christopher Torry, The Autistica Physical Health and Ageing Study Group
Published: 27 April 2020
AMRC Open Research, Volume 2; doi:10.12688/amrcopenres.12901.1

Abstract:
Social Prescribing (SP) is the referral of patients to non-clinical services for practical, physical or psychosocial support. Recent guidelines from the National Health Service England mean that SP will become commonplace for people with complex healthcare needs. Autistic adults make up 1% of the population and commonly have co-existing physical and mental health conditions, therefore they are likely to be referred to SP services. As yet, no studies have examined the efficacy of SP for autistic adults. In this letter, we review the existing literature examining the efficacy of SP in the general population. We further examine the factors that should be considered when offering SP to autistic adults in order to optimise outcomes.
Margaret G. Keane, Hannah R. Dadds, Ghassan El Sayed, Tu Vinh Luong, Brian R. Davidson, Guiseppe K. Fusai, Douglas Thorburn, Stephen P. Pereira
Published: 16 January 2020
AMRC Open Research, Volume 1; doi:10.12688/amrcopenres.12860.2

Abstract:
Background: Pancreatic cystic lesions (PCL) are being detected with increasing frequency. Current methods of stratifying risk of malignant transformation are imperfect. This study aimed to determine the frequency of pancreatic malignancy in patients with PCL and define clinical and radiological features that predict malignant transformation in patients managed by surgery and/or surveillance.
Nele Demeyere, Shuo Sun, Elise Milosevich, Kathleen Vancleef
Published: 13 August 2019
AMRC Open Research, Volume 1; doi:10.12688/amrcopenres.12882.1

Abstract:
Background: Cognitive impairment is common following stroke. The Oxford Cognitive Screen (OCS) was designed to assess focal post-stroke cognitive deficits in five domains. Here, we investigated whether results generated by the OCS vs the domain-general Montreal Cognitive Assessment (MoCA) at baseline impacted patient outcomes at 6 months follow-up. Methods: Patients Results: A total of 821 patients from 37 different hospital or rehabilitation sites (England, UK) were recruited to the OCS-CARE study, with 467 completing 6-month follow-up. Patient outcomes defined by overall SIS scores and changes in NIHSS did not differ between the OCS or MoCA groups. There were high accordance rates between the OCS and MoCA at 6 months, with severity of cognitive impairment reflected in both screening tools. Cognitive performance in both groups over the 6-month follow-up declined in 22% of patients. A larger proportion of OCS group patients demonstrated improvements in cognitive scores (49% vs 40% in MoCA). Conclusions: The type of cognitive screening test did not impact broad stroke outcome measures, and the two screening tools showed a high overall accordance. The results suggest that more of the domain-specific deficits in OCS recover subacutely, providing a more granular picture of cognitive recovery as well as decline. Registration: ISRCTN50857950; registered on 27/03/2014.
Bogna Drozdowska, Carlos A. Celis-Morales, Donald M. Lyall, Terry Quinn
Published: 7 August 2019
AMRC Open Research, Volume 1; doi:10.12688/amrcopenres.12862.2

Abstract:
Background: Findings from studies in older adult populations suggest that measures of social engagement may be associated with health outcomes, including cognitive function. Plausibly the magnitude and direction of this association may differ in stroke. The disabling nature of stroke increases the likelihood of social isolation and stroke survivors are at high risk of cognitive decline. We assessed the association between social engagement and cognitive function in a sample of stroke survivors. Methods: We included available data from stroke survivors in the UK Biobank (N=8776; age range: 40-72; 57.4% male). In a series of regression models, we assessed cross-sectional associations between proxies of social engagement (frequency of family/friend visits, satisfaction with relationships, loneliness, opportunities to confide in someone, participation in social activities) and performance on domain specific cognitive tasks: reaction time, verbal-numerical reasoning, visual memory and prospective memory. We adjusted for demographics, health-, lifestyle-, and stroke-related factors. Accounting for multiple testing, we set our significance threshold at p Results: After adjusting for covariates, we found independent associations between faster reaction times and monthly family visits as compared to no visit (standardised beta=-0.32, 99.7% CI: -0.61 to -0.03, N=4,930); slower reaction times and religious group participation (standardised beta=0.25, 99.7% CI 0.07 to 0.44, N=4,938); and poorer performance on both verbal-numerical reasoning and prospective memory tasks with loneliness (standardised beta=-0.19, 99.7% CI: -0.34 to -0.03, N=2,074; odds ratio=0.66, 99.7% CI: 0.46 to 0.94, N=2,188; respectively). In models where all proxies of social engagement were combined, no associations remained significant. Conclusions: We found limited task-specific associations between cognitive performance and proxies of social engagement, with only loneliness related to two tasks. Further studies are necessary to confirm and improve our understanding of these relationships and investigate the potential to target psychosocial factors to support cognitive function in stroke survivors.
Sarah Northcott, Alan Simpson, Shirley A Thomas, Shashivadan P. Hirani, Chris Flood, Katerina Hilari
Published: 15 July 2019
AMRC Open Research, Volume 1; doi:10.12688/amrcopenres.12873.2

Abstract:
Background: Around a quarter of people post stroke will experience aphasia, a language disability. Having aphasia places someone at risk of becoming depressed and isolated. There is limited evidence for effective interventions to enhance psychological well-being for this client group. A potential intervention is Solution Focused Brief Therapy (SFBT), which supports a person to build meaningful, achievable change through focusing on a person’s skills and resources rather than their deficits. The SOFIA Trial aims to explore the acceptability of SFBT to people with varying presentations of aphasia, including severe aphasia, and to assess the feasibility of conducting a future definitive trial investigating clinical and cost effectiveness. Methods: The trial is a single-blind, randomised, wait-list controlled feasibility trial with nested qualitative research and pilot economic evaluation comparing SFBT plus usual care to usual care alone. The study will recruit 32 participants with aphasia who are ≥6 months post stroke. All participants will be assessed on psychosocial outcome measures at baseline, three, and six months post randomisation by assessors blinded to treatment allocation. Participants will be randomly assigned to intervention group (start intervention immediately post randomisation) or wait-list group (start intervention six months post randomisation). Wait-list group will additionally be assessed nine months post randomisation. The intervention consists of up to six SFBT sessions delivered over three months by speech and language therapists. Participants and therapists will also take part in in-depth interviews exploring their experiences of the study. The pilot economic evaluation will use the EQ-5D-5L measure and an adapted Client Service Receipt Inventory. People with aphasia have been involved in designing and monitoring the trial. Discussion: Given the high levels of depression and isolation, there is a need to investigate effective interventions that enhance the psychological wellbeing of people with aphasia. Trial registration: ClinicalTrials.gov NCT03245060 10/08/2017.
Kelly Hares, Scott Miners, Neil Scolding, Seth Love, Alastair Wilkins
Published: 26 June 2019
AMRC Open Research, Volume 1; doi:10.12688/amrcopenres.12861.2

Abstract:
Background: Early disturbances in axonal transport, before the onset of gross neuropathology, occur in a spectrum of neurodegenerative diseases including Alzheimer’s disease. Kinesin superfamily motor proteins (KIFs) are responsible for anterograde protein transport within the axon of various cellular cargoes, including synaptic and structural proteins. Dysregulated KIF expression has been associated with AD pathology and genetic polymorphisms within kinesin-light chain-1 (KLC1) have been linked to AD susceptibility. We examined the expression of KLC1 in AD, in relation to that of the KLC1 motor complex (KIF5A) and to susceptibility genotypes. Methods: We analysed KLC1 and KIF5A gene and protein expression in midfrontal cortex from 47 AD and 39 control brains. Results: We found that gene expression of both KIF5A and KLC1 increased with Braak tangle stage (0-II vs III-IV and V-VI) but was not associated with significant change at the protein level. We found no effect of KLC1 SNPs on KIF5A or KLC1 expression but KIF5A SNPs that had previously been linked to susceptibility in multiple sclerosis were associated with reduced KIF5A mRNA expression in AD cortex. Conclusions: Future in vitro and in vivo studies are required to understand the cause of upregulated KIF5A and KLC-1 gene expression in AD and any potential downstream consequences on pathogenesis, including any contribution of genetic polymorphisms within the KIF5A gene locus.
Sarah Northcott, Alan Simpson, Shirley A. Thomas, Shashivadan P. Hirani, Chris Flood, Katerina Hilari
Published: 21 May 2019
AMRC Open Research, Volume 1; doi:10.12688/amrcopenres.12873.1

Abstract:
Background: Around a quarter of people post stroke will experience aphasia, a language disability. Having aphasia places someone at risk of becoming depressed and isolated. There is limited evidence for effective interventions to enhance psychological well-being for this client group. A potential intervention is Solution Focused Brief Therapy (SFBT), which supports a person to build meaningful, achievable change through focusing on a person’s skills and resources rather than their deficits. The SOFIA Trial aims to explore the acceptability of SFBT to people with varying presentations of aphasia, including severe aphasia, and to assess the feasibility of conducting a future definitive trial investigating clinical and cost effectiveness. Methods: The trial is a single-blind, randomised, wait-list controlled feasibility trial with nested qualitative research and pilot economic evaluation comparing SFBT plus usual care to usual care alone. The study will recruit 32 participants with aphasia who are ≥6 months post stroke. All participants will be assessed on psychosocial outcome measures at baseline, three, and six months post randomisation by assessors blinded to treatment allocation. Participants will be randomly assigned to intervention group (start intervention immediately post randomisation) or wait-list group (start intervention six months post randomisation). Wait-list group will additionally be assessed nine months post randomisation. The intervention consists of up to six SFBT sessions delivered over three months by speech and language therapists. Participants and therapists will also take part in in-depth interviews exploring their experiences of the study. The pilot economic evaluation will use the EQ-5D-5L measure and an adapted Client Service Receipt Inventory. People with aphasia have been involved in designing and monitoring the trial. Discussion: Given the high levels of depression and isolation, there is a need to investigate effective interventions that enhance the psychological wellbeing of people with aphasia. Trial registration: ClinicalTrials.gov NCT03245060 10/08/2017.
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