The actin-bundling protein Fascin is overexpressed in inflammatory bowel disease and may be important in tissue repair

<b>Background</b> Fascin is associated with increased cell motility in colorectal tumours but is absent from the normal colonic epithelium. We examined the expression of fascin in inflammatory bowel disease (IBD) and its location at regions undergoing restitution and regeneration. Tissue repair is essential for disease remission and we sought to determine the effects of therapeutic modalities on fascin expression and function using an in vitro model.<p></p> <b>Methods</b> Immunohistochemistry was performed on colonic tissue from IBD patients to determine changes in fascin expression and distribution. A human colorectal epithelial cell line was treated with 5-aminosalicylate (a common treatment for IBD), or sodium butyrate to determine the effect on fascin expression and cell motility.<p></p> <b>Results</b> Fascin overexpression was observed in both ulcerative colitis and Crohn's colitis and expression correlated with disease severity. Immunoreactivity was more intense and widespread in Crohn's compared to ulcerative colitis. Interestingly, highly expressing foci were consistently observed at the edges of ulcers where flattened, motile epithelial cells are actively involved in restitution, and also in areas of mucosal regeneration. 5-aminosalicylate reduced fascin expression in colorectal epithelial cells and inhibited their motility. Conversely, sodium butyrate increased fascin expression and stimulated cell motility in the same cells.<p></p> <b>Conclusions</b> Our data shows that fascin is overexpressed in inflammatory bowel disease and its location is indicative of a role in tissue repair. Our in vitro studies show that different therapeutic modalities may have converse effects on fascin expression and may have significant consequences for disease remission and the clinical management of IBD

The origin of the early time optical emission of Swift GRB 080310

We present broadband multi-wavelength observations of GRB 080310 at redshift z = 2.43. This burst was bright and long-lived, and unusual in having extensive optical and near IR follow-up during the prompt phase. Using these data we attempt to simultaneously model the gamma-ray, X-ray, optical and IR emission using a series of prompt pulses and an afterglow component. Initial attempts to extrapolate the high energy model directly to lower energies for each pulse reveal that a spectral break is required between the optical regime and 0.3 keV to avoid over predicting the optical flux. We demonstrate that afterglow emission alone is insufficient to describe all morphology seen in the optical and IR data. Allowing the prompt component to dominate the early-time optical and IR and permitting each pulse to have an independent low energy spectral indices we produce an alternative scenario which better describes the optical light curve. This, however, does not describe the spectral shape of GRB 080310 at early times. The fit statistics for the prompt and afterglow dominated models are nearly identical making it difficult to favour either. However one enduring result is that both models require a low energy spectral index consistent with self absorption for at least some of the pulses identified in the high energy emission model.Comment: 24 pages, 12 figures, 12 tables. Accepted to MNRA

Recommendations from Two Citizens’ Juries on the Surgical Management of Obesity

Background: It is important that guidelines and criteria used to prioritise access to bariatric surgery are informed by the values of the tax-paying public in combination with the expertise of healthcare professionals. Citizens’ juries are increasingly used around the world to engage the public in healthcare decision-making. This study investigated citizens’ juries about prioritising patient access to bariatric surgery in two Australian cities. Objectives: The objective of this study is to examine public priorities for government expenditure on the surgical management of obesity developed through either a one or three-day citizen jury. Subjects/Methods: A three-day jury was held in Brisbane and a one-day jury in Adelaide. Jurors were selected in Brisbane (n = 18) and in Adelaide (n = 12) according to pre-specified criteria. Expert witnesses from various medical disciplines and consumers were cross-examined by jurors. Results: The verdicts of the juries were similar in that both juries agreed bariatric surgery was an important option in the management of obesity and related comorbidities. Recommendations about who should receive treatment differed slightly across the juries. Both juries rejected the use of age as a rationing tool, but managed their objections in different ways. Participants’ experiences of the jury process were positive, but our observations suggested that many variables may influence the nature of the final verdict. Conclusions: Citizen’s juries, even when shorter in duration, can be an effective tool to guide the development of health policy and priorities. However, our study has identified a range of variables that should be considered when designing and running a jury and when interpreting the verdict

Improving the use of research evidence in guideline development: 12. Incorporating considerations of equity

BACKGROUND: The World Health Organization (WHO), like many other organisations around the world, has recognised the need to use more rigorous processes to ensure that health care recommendations are informed by the best available research evidence. This is the 12(th )of a series of 16 reviews that have been prepared as background for advice from the WHO Advisory Committee on Health Research to WHO on how to achieve this. OBJECTIVES: We reviewed the literature on incorporating considerations of equity in guidelines and recommendations. METHODS: We searched PubMed and three databases of methodological studies for existing systematic reviews and relevant methodological research. We did not conduct systematic reviews ourselves. Our conclusions are based on the available evidence, consideration of what WHO and other organisations are doing and logical arguments. KEY QUESTIONS AND ANSWERS: We found few directly relevant empirical methodological studies. These answers are based largely on logical arguments. When and how should inequities be addressed in systematic reviews that are used as background documents for recommendations? • The following question should routinely be considered: Are there plausible reasons for anticipating differential relative effects across disadvantaged and advantaged populations? • If there are plausible reasons for anticipating differential effects, additional evidence should be included in a review to inform judgments about the likelihood of differential effects. What questions about equity should routinely be addressed by those making recommendations on behalf of WHO? • The following additional questions should routinely be considered: • How likely is it that the results of available research are applicable to disadvantaged populations and settings? • How likely are differences in baseline risk that would result in differential absolute effects across disadvantaged and advantaged populations? • How likely is it that there are important differences in trade-offs between the expected benefits and harms across disadvantaged and advantaged populations? • Are there different implications for disadvantaged and advantaged populations, or implications for addressing inequities? What context specific information is needed to inform adaptation and decision making in a specific setting with regard to impacts on equity? • Those making recommendations on behalf of WHO should routinely consider and offer advice about the importance of the following types of context specific data that might be needed to inform adaptation and decision making in a specific setting: • Effect modifiers for disadvantaged populations and for the likelihood of differential effects • Baseline risk in relationship to social and economic status • Utilization and access to care in relationship to social and economic status • Costs in relationship to social and economic status • Ethics and laws that may impact on strategies for addressing inequities • Availability of resources to address inequities What implementation strategies are likely be needed to ensure that recommendations are implemented equitably? • Organisational changes are likely to be important to address inequities. While it may only be possible to consider these in relationship to specific settings, consideration should be given to how best to provide support for identifying and addressing needs for organisational changes. In countries with pervasive inequities institutional, cultural and political changes may first be needed. • Appropriate indicators of social and economic status should be used to monitor the effects of implementing recommendations on disadvantaged populations and on changes in social and economic status

Guidance on priority setting in health care (GPS-Health) : The inclusion of equity criteria not captured by cost-effectiveness analysis

This Guidance for Priority Setting in Health Care (GPS-Health), initiated by the World Health Organization, offers a comprehensive map of equity criteria that are relevant to health care priority setting and should be considered in addition to cost-effectiveness analysis. The guidance, in the form of a checklist, is especially targeted at decision makers who set priorities at national and sub-national levels, and those who interpret findings from cost-effectiveness analysis. It is also targeted at researchers conducting cost-effectiveness analysis to improve reporting of their results in the light of these other criteria. The guidance was develop through a series of expert consultation meetings and involved three steps: i) methods and normative concepts were identified through a systematic review; ii) the review findings were critically assessed in the expert consultation meetings which resulted in a draft checklist of normative criteria; iii) the checklist was validated though an extensive hearing process with input from a range of relevant stakeholders. The GPS-Health incorporates criteria related to the disease an intervention targets (severity of disease, capacity to benefit, and past health loss); characteristics of social groups an intervention targets (socioeconomic status, area of living, gender; race, ethnicity, religion and sexual orientation); and non-health consequences of an intervention (financial protection, economic productivity, and care for others)

The LeVe CPAP System for Oxygen-Efficient CPAP Respiratory Support: Development and Pilot Evaluation

Background: The COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has placed a significant demand on healthcare providers (HCPs) to provide respiratory support for patients with moderate to severe symptoms. Continuous Positive Airway Pressure (CPAP) non-invasive ventilation can help patients with moderate symptoms to avoid the need for invasive ventilation in intensive care. However, existing CPAP systems can be complex (and thus expensive) or require high levels of oxygen, limiting their use in resource-stretched environments. Technical Development + Testing: The LeVe (“Light”) CPAP system was developed using principles of frugal innovation to produce a solution of low complexity and high resource efficiency. The LeVe system exploits the air flow dynamics of electric fan blowers which are inherently suited to delivery of positive pressure at appropriate flow rates for CPAP. Laboratory evaluation demonstrated that performance of the LeVe system was equivalent to other commercially available systems used to deliver CPAP, achieving a 10 cm H2O target pressure within 2.4% RMS error and 50–70% FiO2 dependent with 10 L/min oxygen from a commercial concentrator. Pilot Evaluation: The LeVe CPAP system was tested to evaluate safety and acceptability in a group of ten healthy volunteers at Mengo Hospital in Kampala, Uganda. The study demonstrated that the system can be used safely without inducing hypoxia or hypercapnia and that its use was well-tolerated by users, with no adverse events reported. Conclusions: To provide respiratory support for the high patient numbers associated with the COVID-19 pandemic, healthcare providers require resource efficient solutions. We have shown that this can be achieved through frugal engineering of a CPAP ventilation system, in a system which is safe for use and well-tolerated in healthy volunteers. This approach may also benefit other respiratory conditions which often go unaddressed in Low and Middle Income Countries (LMICs) for want of context-appropriate technology designed for the limited oxygen resources available