Evaluation of Focal Adhesion Mediated Subcellular Curvature Sensing in Response to Engineered Extracellular Matrix

Fibril curvature is bioinstructive to attached cells. Similar to natural healthy tissues, an engineered extracellular matrix can be designed to stimulate cells to adopt desired phenotypes. To take full advantage of the curvature control in biomaterial fabrication methodologies, an understanding of the response to fibril subcellular curvature is required. In this work, we examined morphology, signaling, and function of human cells attached to electrospun nanofibers. We controlled curvature across an order of magnitude using nondegradable poly(methyl methacrylate) (PMMA) attached to a stiff substrate with flat PMMA as a control. Focal adhesion length and the distance of maximum intensity from the geographic center of the vinculin positive focal adhesion both peaked at a fiber curvature of 2.5 μm-1 (both ∼2× the flat surface control). Vinculin experienced slightly less tension when attached to nanofiber substrates. Vinculin expression was also more affected by a subcellular curvature than structural proteins α-tubulin or α-actinin. Among the phosphorylation sites we examined (FAK397, 576/577, 925, and Src416), FAK925 exhibited the most dependance on the nanofiber curvature. A RhoA/ROCK dependance of migration velocity across curvatures combined with an observation of cell membrane wrapping around nanofibers suggested a hybrid of migration modes for cells attached to fibers as has been observed in 3D matrices. Careful selection of nanofiber curvature for regenerative engineering scaffolds and substrates used to study cell biology is required to maximize the potential of these techniques for scientific exploration and ultimately improvement of human health

Factors that affect powered wheelchair use for an adult population: A systematic Review

PurposeThe purpose of the review was to explore current factors affecting the use of a powered wheelchair for an adult person a with a disability.Materials and MethodsThis review followed the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) statement. Information about the characteristics of the studies (type, setting) and perceived barriers and facilitators to powered wheelchair use were extracted using a data extraction sheet. Data synthesis was achieved using narrative synthesis. The quality of the included studies was assessed using the Standard Quality Assessment Criteria for Evaluating Primary Research Papers from a Variety of Fields (SQAC) and the CASP checklist (Critical Appraisal Skills Programme), Centre for Evidence-Based Medicine, SIGN (Scottish Intercollegiate Guidelines Network).ResultsFifteen studies qualified for inclusion in the review. The narrative synthesis produced a conceptual map of reported factors affecting the usability of a powered wheelchair.ConclusionsThis review demonstrates that powered wheelchair use is a multifaceted and multidisciplinary phenomenon that is dependent on numerous interconnected factors including individual adjustment, stakeholder cooperation, societal attitudes, functional performance, and environmental features. Based on the review findings, there are several applied learning outcomes and practical applications to the powered wheelchair prescription and provision.IMPLICATIONS FOR REHABILITATIONThe rejection, misuse or damage of a powered wheelchair can result in condition deterioration and loss of independence for the user.Adult powered wheelchair prescription, maintenance, and use is a multi-faceted process spanning social, individual, environmental, technical and functional, and organisational factors.Individuals in this stakeholder network should aim to account for these interdisciplinary factors when engaging with people who use powered wheelchairs

Detection of Hepatocellular Carcinoma in Hepatitis C Patients: Biomarker Discovery by LC-MS

Hepatocellular carcinoma (HCC) accounts for most cases of liver cancer worldwide; contraction of hepatitis C (HCV) is considered a major risk factor for liver cancer even when individuals have not developed formal cirrhosis. Global, untargeted metabolic profiling methods were applied to serum samples from patients with either HCV alone or HCC (with underlying HCV). The main objective of the study was to identify metabolite based biomarkers associated with cancer risk, with the long term goal of ultimately improving early detection and prognosis. Serum global metabolite profiles from patients with HCC (n=37) and HCV (n=21) were obtained using high performance liquid chromatography-mass spectrometry (HPLC-MS) methods. The selection of statistically significant metabolites for partial least-squares discriminant analysis (PLS-DA) model creation based on biological and statistical significance was contrasted to that of a traditional approach utilizing p-values alone. A PLS-DA model created using the former approach resulted in a model with 92% sensitivity, 95% specificity, and an AUROC of 0.93. A series of PLS-DA models iteratively utilizing three to seven metabolites that were altered significantly (p<0.05) and sufficiently (FC≤0.7 or FC≥1.3) showed the best performance using p-values alone, the PLS-DA model was capable of generating 73% sensitivity, 95% specificity, and an AUROC of 0.92. Metabolic profiles derived from LC-MS readily distinguish patients with HCC and HCV from those with HCV only. Differences in the metabolic profiles between highrisk individuals and HCC indicate the possibility of identifying the early development of liver cancer in at risk patients. The use of biological significance as a selection process prior to PLSDA modeling may offer improved probabilities for translation of newly discovered biomarkers to clinical application

Short Form Report: Supporting Extra Care Tenants to Reintegrate into their Community Post-Covid: An Exploration of Barriers and Facilitators

Project Development: This project is an outcome of the collaborative research partnership established in 2022 between Linc Cymru and the USW Health and Housing Centre of Excellence. The project was funded by Linc Cymru via a Knowledge Exchange Skills Scholarship (KESS) Masters by Research project which was completed by Holly Driscoll and supervised by Dr Phil Tyson, Dr Alexis Jones, Dr Klara Price and Dr Dan Bowers. This report provides a precis of the key findings and recommendations and is submitted alongside the long form thesis which contains a significantly higher level of detail of the project. Background: Anecdotal evidence from Linc staff had suggested that the Covid 19 pandemic had precipitated a decrease in engagement with social activities amongst tenants in Extra Care settings. Social engagement allied with independent and active living are key tenets of the Extra Care model and these are underpinned by Welsh Government aspirations for independence and autonomy amongst older adults. As such, Linc Cymru were keen to understand the barriers to engagement and the potential facilitators which may subsequently increase engagement. Aims: The aim of this study therefore was to understand how key aspects of life changed during the pandemic and how this continued post-pandemic within Extra Care settings. Key factors for exploration were behaviours, environment, quality of life and general living experiences within these settings. Method: The project employed a qualitative design and engaged a multi stakeholder approach. Interviews were conducted with six staff (scheme managers and the community engagement team) and ten Extra Care tenants. The two groups of stakeholders were recruited from three existing extra care schemes in South Wales. Data was collected from May 2022 to June 2022, which was an ideal time frame for initial post COVID interviews to occur after the year of lockdowns and months of restrictions. Reflexive Thematic Analysis (RTA; Braun &amp; Clarke, 2022) was used to analyse the participant responses. Results: Results yielded two staff themes and two tenant themes with each providing several sub-themes. ·       Staff themes: 1.       The Right Environment for Engaging: How to Best Support and Provide Engagement §  Subthemes: (i) Barriers (ii) Knowing your punters; types and levels to engagement 2.       Working in Extra Care through the Pandemic §  Subthemes: (i) The sick got sicker, (ii) Staff health and wellbeing, Staff shift in responsibilities. ·       Staff themes: 3.       Experiences of Living in Extra Care §  Subthemes: (i) What makes a house a home? (ii) Living through a pandemic, &amp; (iii) Social Impact 4.       Engagement and Social Activities §  Subthemes: (i) Facilitators to engagement, (ii) Barriers to engagement. Conclusions: There are a range of conclusions and recommendations derived from this project (see section below for detail). Overall, the recommendations fell into four key categories, (1) Staffing Considerations, (2) Forward Planning, (3) Activity Types, &amp; (4) Accessibility and Inclusivity</p

Mid-Atlantic Wind - Overcoming the Challenges

This study, supported by the US Department of Energy, Wind Powering America Program, Maryland Department of Natural Resources and Chesapeake Bay Foundation, analyzed barriers to wind energy development in the Mid-Atlantic region along with options for overcoming or mitigating them. The Mid-Atlantic States including Delaware, Maryland, North Carolina and Virginia, have excellent wind energy potential and growing demand for electricity, but only two utility-scale projects have been installed to date. Reasons for this apathetic development of wind resources were analyzed and quantified for four markets. Specific applications are: 1) Appalachian mountain ridgeline sites, 2) on coastal plains and peninsulas, 3) at shallow water sites in Delaware and Chesapeake Bays, Albemarle and Pamlico Sounds, and 4) at deeper water sites off the Atlantic coast. Each market has distinctly different opportunities and barriers. The primary barriers to wind development described in this report can be grouped into four categories; state policy and regulatory issues, wind resource technical uncertainty, economic viability, and public interest in environmental issues. The properties of these typologies are not mutually independent and do interact. The report concluded that there are no insurmountable barriers to land-based wind energy projects and they could be economically viable today. Likewise potential sites in sheltered shallow waters in regional bay and sounds have been largely overlooked but could be viable currently. Offshore ocean-based applications face higher costs and technical and wind resource uncertainties. The ongoing research and development program, revision of state incentive policies, additional wind measurement efforts, transmission system expansion, environmental baseline studies and outreach to private developers and stakeholders are needed to reduce barriers to wind energy development