Christian Woman\u27s Board of Missions Golden Jubilee

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Use of next-generation sequencing and candidate gene analysis to identify underlying defects in patients with inherited platelet function disorders

Background: Inherited platelet function disorders (PFDs) are heterogeneous, and identification of the underlying genetic defects is difficult when based solely on phenotypic and clinical features of the patient. Objective: To analyze 329 genes regulating platelet function, number, and size in order to identify candidate gene defects in patients with PFDs. Patients/methods: Targeted analysis of candidate PFD genes was undertaken after next-generation sequencing of exomic DNA from 18 unrelated index cases with PFDs who were recruited into the UK Genotyping and Phenotyping of Platelets (GAPP) study and diagnosed with platelet abnormalities affecting either Gi signaling (n = 12) or secretion (n = 6). The potential pathogenicity of candidate gene defects was assessed using computational predictive algorithms. Results: Analysis of the 329 candidate PFD genes identified 63 candidate defects, affecting 40 genes, among index cases with Gi signaling abnormalities, while 53 defects, within 49 genes, were identified among patients with secretion abnormalities. Homozygous gene defects were more commonly associated with secretion abnormalities. Functional annotation analysis identified distinct gene clusters in the two patient subgroups. Thirteen genes with significant annotation enrichment for 'intracellular signaling' harbored 16 of the candidate gene defects identified in nine index cases with Gi signaling abnormalities. Four gene clusters, representing 14 genes, with significantly associated gene ontology annotations were identified among the cases with secretion abnormalities, the most significant association being with 'establishment of protein localization.' Conclusion: Our findings demonstrate the genetic complexity of PFDs and highlight plausible candidate genes for targeted analysis in patients with platelet secretion and Gi signaling abnormalities

Walk with Me: a protocol for a pilot RCT of a peer-led walking programme to increase physical activity in inactive older adults

Background: Levels of physical activity decline with age. Some of the most disadvantaged individuals in society, such as those from lower socio-economic position, are also the most inactive. Increasing physical activity levels, particularly among those most inactive, is a public health priority. Peer-led physical activity interventions may offer a model to increase physical activity in the older adult population. This study aims to test the feasibility of a peer-led, multicomponent physical activity intervention in socio-economically disadvantaged community dwelling older adults. Methods: The Medical Research Council framework for developing and evaluating complex interventions will be used to design and test the feasibility of a randomised controlled trial (RCT) of a multicomponent peer-led physical activity intervention. Data will be collected at baseline, immediately after the intervention (12 weeks) and 6 months after baseline measures. The pilot RCT will provide information on recruitment of peer mentors and participants and attrition rates, intervention fidelity, and data on the variability of the primary outcome (minutes of moderate to vigorous physical activity measured with an accelerometer). The pilot trail will also assess the acceptability of the intervention and identify potential resources needed to undertake a definitive study. Data analyses will be descriptive and include an evaluation of eligibility, recruitment, and retention rates. The findings will be used to estimate the sample size required for a definitive trial. A detailed process evaluation using qualitative and quantitative methods will be conducted with a variety of stakeholders to identify areas of success and necessary improvements. Discussion: This paper describes the protocol for the ‘Walk with Me’ pilot RCT which will provide the information necessary to inform the design and delivery of a fully powered trial should the Walk with Me intervention prove feasible

Around the tangent cone theorem

A cornerstone of the theory of cohomology jump loci is the Tangent Cone theorem, which relates the behavior around the origin of the characteristic and resonance varieties of a space. We revisit this theorem, in both the algebraic setting provided by cdga models, and in the topological setting provided by fundamental groups and cohomology rings. The general theory is illustrated with several classes of examples from geometry and topology: smooth quasi-projective varieties, complex hyperplane arrangements and their Milnor fibers, configuration spaces, and elliptic arrangements.Comment: 39 pages; to appear in the proceedings of the Configurations Spaces Conference (Cortona 2014), Springer INdAM serie

From START to FINISH : the influence of osmotic stress on the cell cycle

Peer reviewedPublisher PD

An app-, web- and social support-based weight loss intervention for adults with obesity: the 'HelpMeDoIt!' feasibility randomised controlled trial

This is the final version. Available on open access from BMC via the DOI in this recordAvailability of data and materials: The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.Background: Social support has an important role in successful weight loss. The aim of this study was to assess the feasibility and acceptability of an app-, web- and social support-based intervention in supporting adults with obesity to achieve weight loss. Methods: The intervention and evaluation methods were tested in a feasibility randomised controlled trial. Adults in the Greater Glasgow and Clyde Health Board area of Scotland with a body mass index ≥ 30 kg/m2 were recruited and randomised 2:1 (intervention to control). The feasibility and acceptability of the intervention and trial methods were assessed against pre-specified progression criteria, via process, economic and outcome evaluation. Three primary outcomes were explored: BMI, diet and physical activity, as well as a number of secondary outcomes. The intervention group had access to the HelpMeDoIt! intervention for 12 months. This encouraged them to (i) set goals, (ii) monitor progress and (iii) harness social support by inviting 'helpers' from their existing social network. The control group received a healthy lifestyle leaflet. Results: One hundred and nine participants were recruited, with 84 participants (77%) followed-up at 12 months. The intervention and trial methods were feasible and acceptable. Participants and helpers were generally positive. Of the 54 (74%) participants who downloaded the app, 48 (89%) used it. Interview data indicated that HelpMeDoIt! promoted social support from existing social networks to support weight loss. This support was often given outside of the app.Outcomes were compared using linear regression models, with randomised group, the baseline measurement of the outcome, age and gender as predictor variables. These analyses were exploratory and underpowered to detect effects. However, all pre-specified primary outcome effects (BMI, diet and physical activity) had wide confidence intervals and were therefore consistent with clinically relevant benefits. Objective physical activity measures perhaps showed most potential (daily step count (p = 0.098; 1187 steps [- 180, 2555])) and sedentary time (p = 0.022; - 60.8 min [- 110.5, - 11.0]). However, these outcomes were poorly completed. Conclusions: The study demonstrated that a novel social support intervention involving support from participants' close social networks, delivered via app and website, has potential to promote weight loss and is feasible and acceptable. Trial registration: ISRCTN, ISRCTN85615983. Registered 25 September 2014.National Institute for Health Research (NIHR)Medical Research Council (MRC)Chief Scientist Office Social and Public Health Sciences Uni

Peer-led walking programme to increase physical activity in inactive 60- to 70-year-olds: Walk with Me pilot RCT

Background Levels of physical activity decline with age. Some of the most disadvantaged individuals in society, such as those with a lower rather than a higher socioeconomic position, are also the most inactive. Peer-led physical activity interventions may offer a model to increase physical activity in these older adults and thus help reduce associated health inequalities. This study aims to develop and test the feasibility of a peer-led, multicomponent physical activity intervention in socioeconomically disadvantaged community-dwelling older adults. Objectives The study aimed to develop a peer-led intervention through a rapid review of previous peer-led interventions and interviews with members of the target population. A proposed protocol to evaluate its effectiveness was tested in a pilot randomised controlled trial (RCT). Design A rapid review of the literature and the pilot study informed the intervention design; a pilot RCT included a process evaluation of intervention delivery. Setting Socioeconomically disadvantaged communities in the South Eastern Health and Social Care Trust and the Northern Health and Social Care Trust in Northern Ireland. Participants Fifty adults aged 60–70 years, with low levels of physical activity, living in socioeconomically disadvantaged communities, recruited though community organisations and general practices. Interventions ‘Walk with Me’ is a 12-week peer-led walking intervention based on social cognitive theory. Participants met weekly with peer mentors. During the initial period (weeks 1–4), each intervention group participant wore a pedometer and set weekly step goals with their mentor’s support. During weeks 5–8 participants and mentors met regularly to walk and discuss step goals and barriers to increasing physical activity. In the final phase (weeks 9–12), participants and mentors continued to set step goals and planned activities to maintain their activity levels beyond the intervention period. The control group received only an information booklet on active ageing. Main outcome measures Rates of recruitment, retention of participants and completeness of the primary outcome [moderate- and vigorous-intensity physical activity measured using an ActiGraph GT3X+ accelerometer (ActiGraph, LLC, Pensacola, FL, USA) at baseline, 12 weeks (post intervention) and 6 months]; acceptability assessed through interviews with participants and mentors. Results The study planned to recruit 60 participants. In fact, 50 eligible individuals participated, of whom 66% (33/50) were female and 80% (40/50) were recruited from general practices. At 6 months, 86% (43/50) attended for review, 93% (40/43) of whom returned valid accelerometer data. Intervention fidelity was assessed by using weekly step diaries, which were completed by both mentors and participants for all 12 weeks, and checklists for the level of delivery of intervention components, which was high for the first 3 weeks (range 49–83%). However, the rate of return of checklists by both mentors and participants diminished thereafter. Outcome data indicate that a sample size of 214 is required for a definitive trial. Limitations The sample was predominantly female and somewhat active. Conclusions The ‘Walk with Me’ intervention is acceptable to a socioeconomically disadvantaged community of older adults and a definitive RCT to evaluate its effectiveness is feasible. Some modifications are required to ensure fidelity of intervention delivery is optimised. Future research needs to identify methods to recruit males and less active older adults into physical activity interventions

Common health assets protocol: a mixed-methods, realist evaluation and economic appraisal of how community-led organisations (CLOs) impact on the health and well-being of people living in deprived areas

Introduction: This research investigates how community-led organisations’ (CLOs’) use of assets-based approaches improves health and well-being, and how that might be different in different contexts. Assets-based approaches involve ‘doing with’ rather than ‘doing to’ and bring people in communities together to achieve positive change using their own knowledge, skills and experience. Some studies have shown that such approaches can have a positive effect on health and well-being. However, research is limited, and we know little about which approaches lead to which outcomes and how different contexts might affect success. Methods and analysis: Using a realist approach, we will work with 15 CLOs based in disadvantaged communities in England, Scotland and Northern Ireland. A realist synthesis of review papers, and a policy analysis in different contexts, precedes qualitative interviews and workshops with stakeholders, to find out how CLOs’ programmes work and identify existing data. We will explore participants’ experiences through: a Q methodology study; participatory photography workshops; qualitative interviews and measure outcomes using a longitudinal survey, with 225 CLO participants, to assess impact for people who connect with the CLOs. An economic analysis will estimate costs and benefits to participants, for different contexts and mechanisms. A ‘Lived Experience Panel’ of people connected with our CLOs as participants or volunteers, will ensure the appropriateness of the research, interpretation and reporting of findings. Ethics and dissemination: This project, research tools and consent processes have been approved by the Glasgow Caledonian University School of Health and Life Sciences Ethics Committee, and affirmed by Ethics Committees at Bournemouth University, Queen’s University Belfast and the University of East London. Common Health Assets does not involve any National Health Service sites, staff or patients. Findings will be presented through social media, project website, blogs, policy briefings, journal articles, conferences and visually in short digital stories, and photographic exhibitions