Risk factors for transmission of Ebola or Marburg virus disease: a systematic review and meta-analysis

Background The Ebola virus disease outbreak that started in Western Africa in 2013 was unprecedented because it spread within densely populated urban environments and affected many thousands of people. As a result, previous advice and guidelines need to be critically reviewed, especially with regard to transmission risks in different contexts. Methods Scientific and grey literature were searched for articles about any African filovirus. Articles were screened for information about transmission (prevalence or odds ratios especially). Data were extracted from eligible articles and summarised narratively with partial meta-analysis. Study quality was also evaluated. Results 31 reports were selected from 6552 found in the initial search. Eight papers gave numerical odds for contracting filovirus illness, 23 further articles provided supporting anecdotal observations about how transmission probably occurred for individuals. Many forms of contact (conversation, sharing a meal, sharing a bed, direct or indirect touching) were unlikely to result in disease transmission during incubation or early illness. Amongst household contacts who reported directly touching a case, the attack rate was 32% (95% CI 26-38%). Risk of disease transmission between household members without direct contact was low (1%; 95% CI 0-5%). Caring for a case in the community, especially until death, and participation in traditional funeral rites were strongly associated with acquiring disease, probably due to a high degree of direct physical contact with case or cadaver. Conclusions Transmission of filovirus is unlikely except through close contact, especially during the most severe stages of acute illness. More data are needed about the context, intimacy and timing of contact required to raise the odds of disease transmission. Risk factors specific to urban settings may need to be determined

Student Belonging Good Practice Guide

This Good Practice Guide offers a toolkit and a conversation starter for anyone working in higher education (HE) who is thinking about embarking on a student belonging project. As well as sharing hints and tips, it draws upon student belonging insights via case studies, an extended literature review and student voice. We aim to provide those of you working within student partnerships or with a professional interest in student engagement easy access to key definitions and debates in the field of student belonging. As this guide provides a shorthand to the contexts of student belonging, we anticipate readers may wish to use the ideas presented here during your curriculum planning or project setting phase, to ensure student voice, orientation and partnership working are at the core of your academic lifecycles and institutional activity preparations. We hope this guide will help you to facilitate communication, influence policy and encourage focus and investment in student engagement in your institution. We believe in being inclusive so much of what you read below will describe student belonging and engagement through this lens. Through our case studies this guide will touch on key themes aligned to student belonging and engagement: student voice, student-staff collaborative working, transitions and orientation, the student journey/lifecycle. These cases are a work in progress – we don’t have all the answers (yet) but we do hope it will be useful to those of you who are looking to explore methods to gain further insights into student mattering, engagement and identity. We will discuss initial findings and the next steps that the partner institutions have adopted but in the main these case studies will set the scene for others wishing to follow suit. Throughout the case studies we offer tools for colleagues in higher education institutions (HEI) to use – these include pre-arrival survey questions, and activities to harness self-perceived student identity and attachment to the university. However, these are not prescriptive; we recognise that each institution will need – and should, in the name of good practice – use these as conversation starters or prompts for approaches that are specific and tailored to your institution and its unique student body.This guide is the output of a RAISE Network-funded project, in partnership with Teesside University, Edinburgh Napier University and Nottingham Trent University. Researching Advancing and Inspiring Student Engagement (RAISE) is a worldwide network of staff and students in HE who work or have an interest in the research and promotion of student engagemen

Epoxy–amine oligomers from terpenes with applications in synergistic antifungal treatments

A bis-epoxide monomer was synthesised in two steps from (R)-carvone, a terpenoid renewable feedstock derived from spearmint oil, and used to prepare β-aminoalcohol oligomers in polyaddition reactions with bis-amines without requiring solvent or catalyst. A sub-set of the resultant materials were readily water soluble and were investigated for antifungal activity in combination with the fungicide iodopropynyl-butylcarbamate (IPBC) or the antifungal drug amphotericin B. The oligo-(β-aminoalcohol)s alone were inactive against Trichoderma virens and Candida albicans but in combination with IPBC and amphotericin B demonstrated synergistic growth-inhibition of both fungi. Quantitative analysis showed that the presence of the terpene-based oligomers decreased the minimum inhibitory concentration (MIC) of IPBC by up to 64-fold and of amphotericin B by 8-fold. The efficacy of the combined formulation was further demonstrated with agar disk diffusion assays, which revealed that IPBC and amphotericin B reduced the growth of the fungi, as shown by zones of inhibition, to a greater extent when in the presence of the oligo-(β-aminoalcohol)s. These data suggest potential future use of these renewable feedstock derived oligomers in antifungal material and related biomedical applications

A randomised controlled trial assessing the use of citalopram, sertraline, fluoxetine and mirtazapine in preventing relapse in primary care patients who are taking long-term maintenance antidepressants (ANTLER : ANTidepressants to prevent reLapse in dEpRession): study protocol for a randomised controlled trial

BACKGROUND: Antidepressants are used both for treating acute episodes and for prophylaxis to prevent future episodes of depression, also called maintenance treatment. This article describes the protocol for a randomised controlled trial (ANTLER: ANTidepressants to prevent reLapse in dEpRession) to investigate the clinical effectiveness and cost-effectiveness in UK primary care of continuing on long-term maintenance antidepressants compared with a placebo in preventing relapse of depression in those who have taken antidepressants for more than 9 months and who are currently well enough to consider stopping maintenance treatment. METHODS/DESIGN: The ANTLER trial is an individually randomised, double-blind, placebo-controlled trial in which participants are randomised to remain on active medication or to take an identical placebo after a tapering period of 2 months. Eligible participants are those who: are between the ages of 18 and 74 years; have had at least two episodes of depression; and have been taking antidepressants for 9 months or more and are currently taking citalopram 20 mg, sertraline 100 mg, fluoxetine 20 mg or mirtazapine 30 mg but are well enough to consider stopping their medication. The participants will be followed up at 6, 12, 26, 39 and 52 weeks. The primary outcome will be the time in weeks to the beginning of the first episode of depression after randomisation. This will be measured using a retrospective version of the Clinical Interview Schedule-Revised administered at 12, 26, 39 and 52 weeks. Secondary outcomes will include depressive and anxiety symptoms, adverse effects, withdrawal symptoms, emotional processing tasks, quality of life and the resources and costs used. We will also perform a cost-effectiveness analysis based on results of the trial. DISCUSSION: The ANTLER trial findings will inform primary care prescribing practice by providing a valid and generalisable estimate of the clinical effectiveness and cost-effectiveness of long-term maintenance treatment with antidepressants in UK primary care. TRIAL REGISTRATION: Controlled Trials ISRCTN Registry, ISRCTN15969819. Registered on 21 September 2015

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

The twilight of the Liberal Social Contract? On the Reception of Rawlsian Political Liberalism

This chapter discusses the Rawlsian project of public reason, or public justification-based 'political' liberalism, and its reception. After a brief philosophical rather than philological reconstruction of the project, the chapter revolves around a distinction between idealist and realist responses to it. Focusing on political liberalism’s critical reception illuminates an overarching question: was Rawls’s revival of a contractualist approach to liberal legitimacy a fruitful move for liberalism and/or the social contract tradition? The last section contains a largely negative answer to that question. Nonetheless the chapter's conclusion shows that the research programme of political liberalism provided and continues to provide illuminating insights into the limitations of liberal contractualism, especially under conditions of persistent and radical diversity. The programme is, however, less receptive to challenges to do with the relative decline of the power of modern states

Constitutivism

A brief explanation and overview of constitutivism

Cumulative Burden of Colorectal Cancer-Associated Genetic Variants Is More Strongly Associated With Early-Onset vs Late-Onset Cancer.

BACKGROUND & AIMS: Early-onset colorectal cancer (CRC, in persons younger than 50 years old) is increasing in incidence; yet, in the absence of a family history of CRC, this population lacks harmonized recommendations for prevention. We aimed to determine whether a polygenic risk score (PRS) developed from 95 CRC-associated common genetic risk variants was associated with risk for early-onset CRC. METHODS: We studied risk for CRC associated with a weighted PRS in 12,197 participants younger than 50 years old vs 95,865 participants 50 years or older. PRS was calculated based on single nucleotide polymorphisms associated with CRC in a large-scale genome-wide association study as of January 2019. Participants were pooled from 3 large consortia that provided clinical and genotyping data: the Colon Cancer Family Registry, the Colorectal Transdisciplinary Study, and the Genetics and Epidemiology of Colorectal Cancer Consortium and were all of genetically defined European descent. Findings were replicated in an independent cohort of 72,573 participants. RESULTS: Overall associations with CRC per standard deviation of PRS were significant for early-onset cancer, and were stronger compared with late-onset cancer (P for interaction = .01); when we compared the highest PRS quartile with the lowest, risk increased 3.7-fold for early-onset CRC (95% CI 3.28-4.24) vs 2.9-fold for late-onset CRC (95% CI 2.80-3.04). This association was strongest for participants without a first-degree family history of CRC (P for interaction = 5.61 × 10-5). When we compared the highest with the lowest quartiles in this group, risk increased 4.3-fold for early-onset CRC (95% CI 3.61-5.01) vs 2.9-fold for late-onset CRC (95% CI 2.70-3.00). Sensitivity analyses were consistent with these findings. CONCLUSIONS: In an analysis of associations with CRC per standard deviation of PRS, we found the cumulative burden of CRC-associated common genetic variants to associate with early-onset cancer, and to be more strongly associated with early-onset than late-onset cancer, particularly in the absence of CRC family history. Analyses of PRS, along with environmental and lifestyle risk factors, might identify younger individuals who would benefit from preventive measures

Discovery of common and rare genetic risk variants for colorectal cancer.

To further dissect the genetic architecture of colorectal cancer (CRC), we performed whole-genome sequencing of 1,439 cases and 720 controls, imputed discovered sequence variants and Haplotype Reference Consortium panel variants into genome-wide association study data, and tested for association in 34,869 cases and 29,051 controls. Findings were followed up in an additional 23,262 cases and 38,296 controls. We discovered a strongly protective 0.3% frequency variant signal at CHD1. In a combined meta-analysis of 125,478 individuals, we identified 40 new independent signals at P < 5 × 10-8, bringing the number of known independent signals for CRC to ~100. New signals implicate lower-frequency variants, Krüppel-like factors, Hedgehog signaling, Hippo-YAP signaling, long noncoding RNAs and somatic drivers, and support a role for immune function. Heritability analyses suggest that CRC risk is highly polygenic, and larger, more comprehensive studies enabling rare variant analysis will improve understanding of biology underlying this risk and influence personalized screening strategies and drug development.Goncalo R Abecasis has received compensation from 23andMe and Helix. He is currently an employee of Regeneron Pharmaceuticals. Heather Hampel performs collaborative research with Ambry Genetics, InVitae Genetics, and Myriad Genetic Laboratories, Inc., is on the scientific advisory board for InVitae Genetics and Genome Medical, and has stock in Genome Medical. Rachel Pearlman has participated in collaborative funded research with Myriad Genetics Laboratories and Invitae Genetics but has no financial competitive interest