Mapping Public Engagement with Research in a UK University

Notwithstanding that ‘public engagement’ is conceptualised differently internationally and in different academic disciplines, higher education institutions largely accept the importance of public engagement with research. However, there is limited evidence on how researchers conceptualise engagement, their views on what constitutes engagement and the communities they would (or would not) like to engage with. This paper presents the results of a survey of researchers in the Open University that sought to gather data to fill these gaps. This research was part of an action research project designed to embed engagement in the routine practices of researchers at all levels. The findings indicate that researchers have a relatively narrow view of public engagement with research and the communities with which they interact. It also identified that very few strategically evaluate their public engagement activities. We conclude by discussing some of the interventions we have introduced with the aim of broadening and deepening future researcher engagement

MscS-like mechanosensitive channels in plants and microbes

The challenge of osmotic stress is something all living organisms must face as a result of environmental dynamics. Over the past three decades, innovative research and cooperation across disciplines have irrefutably established that cells utilize mechanically gated ion channels to release osmolytes and prevent cell lysis during hypoosmotic stress. Early electrophysiological analysis of the inner membrane of Escherichia coli identified the presence of three distinct mechanosensitive activities. The subsequent discoveries of the genes responsible for two of these activities, the mechanosensitive channels of large (MscL) and small (MscS) conductance, led to the identification of two diverse families of mechanosensitive channels. The latter of these two families, the MscS family, consists of members from bacteria, archaea, fungi, and plants. Genetic and electrophysiological analysis of these family members has provided insight into how organisms use mechanosensitive channels for osmotic regulation in response to changing environmental and developmental circumstances. Furthermore, determining the crystal structure of E. coli MscS and several homologues in several conformational states has contributed to our understanding of the gating mechanisms of these channels. Here we summarize our current knowledge of MscS homologues from all three domains of life and address their structure, proposed physiological functions, electrophysiological behaviors, and topological diversity

Mid-Holocene pulse of thinning in the Weddell Sea sector of the West Antarctic ice sheet

Establishing the trajectory of thinning of the West Antarctic ice sheet (WAIS) since the last glacial maximum (LGM) is important for addressing questions concerning ice sheet (in)stability and changes in global sea level. Here we present detailed geomorphological and cosmogenic nuclide data from the southern Ellsworth Mountains in the heart of the Weddell Sea embayment that suggest the ice sheet, nourished by increased snowfall until the early Holocene, was close to its LGM thickness at 10 ka. A pulse of rapid thinning caused the ice elevation to fall ~400 m to the present level at 6.5–3.5 ka, and could have contributed 1.4–2 m to global sea-level rise. These results imply that the Weddell Sea sector of the WAIS contributed little to late-glacial pulses in sea-level rise but was involved in mid-Holocene rises. The stepped decline is argued to reflect marine downdraw triggered by grounding line retreat into Hercules Inlet

The experience of living with chronic heart failure: a narrative review of qualitative studies

<p>Abstract</p> <p>Background</p> <p>Chronic heart failure (CHF) is the leading cause of all hospitalisations and readmissions in older people, accounting for a large proportion of developed countries' national health care expenditure. CHF can severely affect people's quality of life by reducing their independence and ability to undertake certain activities of daily living, as well as affecting their psychosocial and economic capacity. This paper reports the findings of a systematic narrative review of qualitative studies concerning people's experience of living with CHF, aiming to develop a wide-ranging understanding of what is known about the patient experience.</p> <p>Methods</p> <p>We searched eight relevant electronic databases using the terms based on the diagnosis of 'chronic heart failure', 'heart failure' and 'congestive heart failure' and qualitative methods, with restrictions to the years 1990-May 2008. We also used snowballing, hand searching and the expert knowledge of the research team to ensure all relevant papers were included in the review. Of 65 papers collected less than half (n = 30) were found relevant for this review. These papers were subsequently summarised and entered into QSR NVivo7 for data management and analysis.</p> <p>Results</p> <p>The review has identified the most prominent impacts of CHF on a person's everyday life including social isolation, living in fear and losing a sense of control. It has also identified common strategies through which patients with CHF manage their illness such as sharing experiences and burdens with others and being flexible to changing circumstances.</p> <p>Finally, there are multiple factors that commonly impact on patients' self care and self-management in the disease trajectory including knowledge, understanding and health service encounters. These health service encounters encompass access, continuity and quality of care, co-morbid conditions, and personal relationships.</p> <p>Conclusions</p> <p>The core and sub-concepts identified within this study provide health professionals, service providers, policy makers and educators with broad insights into common elements of people's experiences of CHF and potential options for improving their health and wellbeing. Future studies should focus on building a comprehensive picture of CHF through examination of differences between genders, and differences within age groups, socioeconomic groups and cultural groups.</p

Outer membrane protein size and LPS O-antigen define protective antibody targeting to the Salmonella surface

Lipopolysaccharide (LPS) O-antigen (O-Ag) is known to limit antibody binding to surface antigens, although the relationship between antibody, O-Ag and other outer-membrane antigens is poorly understood. Here we report, immunization with the trimeric porin OmpD from Salmonella Typhimurium (STmOmpD) protects against infection. Atomistic molecular dynamics simulations indicate this is because OmpD trimers generate footprints within the O-Ag layer sufficiently sized for a single IgG Fab to access. While STmOmpD differs from its orthologue in S. Enteritidis (SEn) by a single amino-acid residue, immunization with STmOmpD confers minimal protection to SEn. This is due to the OmpD-O-Ag interplay restricting IgG binding, with the pairing of OmpD with its native O-Ag being essential for optimal protection after immunization. Thus, both the chemical and physical structure of O-Ag are key for the presentation of specific epitopes within proteinaceous surface-antigens. This enhances combinatorial antigenic diversity in Gram-negative bacteria, while reducing associated fitness costs

Natural History of Tuberculosis: Duration and Fatality of Untreated Pulmonary Tuberculosis in HIV Negative Patients: A Systematic Review

Background The prognosis, specifically the case fatality and duration, of untreated tuberculosis is important as many patients are not correctly diagnosed and therefore receive inadequate or no treatment. Furthermore, duration and case fatality of tuberculosis are key parameters in interpreting epidemiological data. Methodology and Principal Findings To estimate the duration and case fatality of untreated pulmonary tuberculosis in HIV negative patients we reviewed studies from the pre-chemotherapy era. Untreated smear-positive tuberculosis among HIV negative individuals has a 10-year case fatality variously reported between 53% and 86%, with a weighted mean of 70%. Ten-year case fatality of culture-positive smear-negative tuberculosis was nowhere reported directly but can be indirectly estimated to be approximately 20%. The duration of tuberculosis from onset to cure or death is approximately 3 years and appears to be similar for smear-positive and smear-negative tuberculosis. Conclusions Current models of untreated tuberculosis that assume a total duration of 2 years until self-cure or death underestimate the duration of disease by about one year, but their case fatality estimates of 70% for smear-positive and 20% for culture-positive smear-negative tuberculosis appear to be satisfactory

Citizen science breathes new life into participatory agricultural research : A review

Participatory research can improve the efficiency, effectiveness, and scope of research processes, and foster social inclusion, empowerment and sustainability. Yet despite four decades of agricultural research institutions exploring and developing methods for participatory research, it has never become mainstream in the agricultural technology development cycle. Citizen science promises an innovative approach to participation in research, using the unique facilities of new digital technologies, but its potential in agricultural research participation has not been systematically probed. To this end, we conducted a critical literature review. We found that citizen science opens up four opportunities for creatively reshaping research: i) new possibilities for interdisciplinary collaboration, ii) rethinking configurations of socio-computational systems, iii) research on democratization of science more broadly, and iv) new accountabilities. Citizen science also brings a fresh perspective on the barriers to institutionalizing participation in the agricultural sciences. Specifically, we show how citizen science can reconfigure cost-motivation-accountability combinations using digital tools, open up a larger conceptual space of experimentation, and stimulate new collaborations. With appropriate and persistent institutional support and investment, citizen science can therefore have a lasting impact on how agricultural science engages with farming communities and wider society, and more fully realize the promises of participation

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2–4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

Global patient outcomes after elective surgery: prospective cohort study in 27 low-, middle- and high-income countries.

BACKGROUND: As global initiatives increase patient access to surgical treatments, there remains a need to understand the adverse effects of surgery and define appropriate levels of perioperative care. METHODS: We designed a prospective international 7-day cohort study of outcomes following elective adult inpatient surgery in 27 countries. The primary outcome was in-hospital complications. Secondary outcomes were death following a complication (failure to rescue) and death in hospital. Process measures were admission to critical care immediately after surgery or to treat a complication and duration of hospital stay. A single definition of critical care was used for all countries. RESULTS: A total of 474 hospitals in 19 high-, 7 middle- and 1 low-income country were included in the primary analysis. Data included 44 814 patients with a median hospital stay of 4 (range 2-7) days. A total of 7508 patients (16.8%) developed one or more postoperative complication and 207 died (0.5%). The overall mortality among patients who developed complications was 2.8%. Mortality following complications ranged from 2.4% for pulmonary embolism to 43.9% for cardiac arrest. A total of 4360 (9.7%) patients were admitted to a critical care unit as routine immediately after surgery, of whom 2198 (50.4%) developed a complication, with 105 (2.4%) deaths. A total of 1233 patients (16.4%) were admitted to a critical care unit to treat complications, with 119 (9.7%) deaths. Despite lower baseline risk, outcomes were similar in low- and middle-income compared with high-income countries. CONCLUSIONS: Poor patient outcomes are common after inpatient surgery. Global initiatives to increase access to surgical treatments should also address the need for safe perioperative care. STUDY REGISTRATION: ISRCTN5181700

Effect of SGLT2 inhibitors on stroke and atrial fibrillation in diabetic kidney disease: Results from the CREDENCE trial and meta-analysis

BACKGROUND AND PURPOSE: Chronic kidney disease with reduced estimated glomerular filtration rate or elevated albuminuria increases risk for ischemic and hemorrhagic stroke. This study assessed the effects of sodium glucose cotransporter 2 inhibitors (SGLT2i) on stroke and atrial fibrillation/flutter (AF/AFL) from CREDENCE (Canagliflozin and Renal Events in Diabetes With Established Nephropathy Clinical Evaluation) and a meta-Analysis of large cardiovascular outcome trials (CVOTs) of SGLT2i in type 2 diabetes mellitus. METHODS: CREDENCE randomized 4401 participants with type 2 diabetes mellitus and chronic kidney disease to canagliflozin or placebo. Post hoc, we estimated effects on fatal or nonfatal stroke, stroke subtypes, and intermediate markers of stroke risk including AF/AFL. Stroke and AF/AFL data from 3 other completed large CVOTs and CREDENCE were pooled using random-effects meta-Analysis. RESULTS: In CREDENCE, 142 participants experienced a stroke during follow-up (10.9/1000 patient-years with canagliflozin, 14.2/1000 patient-years with placebo; hazard ratio [HR], 0.77 [95% CI, 0.55-1.08]). Effects by stroke subtypes were: ischemic (HR, 0.88 [95% CI, 0.61-1.28]; n=111), hemorrhagic (HR, 0.50 [95% CI, 0.19-1.32]; n=18), and undetermined (HR, 0.54 [95% CI, 0.20-1.46]; n=17). There was no clear effect on AF/AFL (HR, 0.76 [95% CI, 0.53-1.10]; n=115). The overall effects in the 4 CVOTs combined were: Total stroke (HRpooled, 0.96 [95% CI, 0.82-1.12]), ischemic stroke (HRpooled, 1.01 [95% CI, 0.89-1.14]), hemorrhagic stroke (HRpooled, 0.50 [95% CI, 0.30-0.83]), undetermined stroke (HRpooled, 0.86 [95% CI, 0.49-1.51]), and AF/AFL (HRpooled, 0.81 [95% CI, 0.71-0.93]). There was evidence that SGLT2i effects on total stroke varied by baseline estimated glomerular filtration rate (P=0.01), with protection in the lowest estimated glomerular filtration rate (45 mL/min/1.73 m2]) subgroup (HRpooled, 0.50 [95% CI, 0.31-0.79]). CONCLUSIONS: Although we found no clear effect of SGLT2i on total stroke in CREDENCE or across trials combined, there was some evidence of benefit in preventing hemorrhagic stroke and AF/AFL, as well as total stroke for those with lowest estimated glomerular filtration rate. Future research should focus on confirming these data and exploring potential mechanisms