Effect of reheating on predictions following multiple-field inflation

We study the sensitivity of cosmological observables to the reheating phase following inflation driven by many scalar fields. We describe a method which allows semi-analytic treatment of the impact of perturbative reheating on cosmological perturbations using the sudden decay approximation. Focusing on $\mathcal{N}$-quadratic inflation, we show how the scalar spectral index and tensor-to-scalar ratio are affected by the rates at which the scalar fields decay into radiation. We find that for certain choices of decay rates, reheating following multiple-field inflation can have a significant impact on the prediction of cosmological observables.Comment: Published in PRD. 4 figures, 10 page

Two spatial scales in a bleaching event : corals from the mildest and the most extreme thermal environments escape mortality

Author Posting. © Association for the Sciences of Limnology and Oceanography, 2013. This article is posted here by permission of Association for the Sciences of Limnology and Oceanography for personal use, not for redistribution. The definitive version was published in Limnology and Oceanography 58 (2013): 1531-1545, doi:10.4319/lo.2013.58.5.1531.In summer 2010, a bleaching event decimated the abundant reef flat coral Stylophora pistillata in some areas of the central Red Sea, where a series of coral reefs 100–300 m wide by several kilometers long extends from the coastline to about 20 km offshore. Mortality of corals along the exposed and protected sides of inner (inshore) and mid and outer (offshore) reefs and in situ and satellite sea surface temperatures (SSTs) revealed that the variability in the mortality event corresponded to two spatial scales of temperature variability: 300 m across the reef flat and 20 km across a series of reefs. However, the relationship between coral mortality and habitat thermal severity was opposite at the two scales. SSTs in summer 2010 were similar or increased modestly (0.5°C) in the outer and mid reefs relative to 2009. In the inner reef, 2010 temperatures were 1.4°C above the 2009 seasonal maximum for several weeks. We detected little or no coral mortality in mid and outer reefs. In the inner reef, mortality depended on exposure. Within the inner reef, mortality was modest on the protected (shoreward) side, the most severe thermal environment, with highest overall mean and maximum temperatures. In contrast, acute mortality was observed in the exposed (seaward) side, where temperature fluctuations and upper water temperature values were relatively less extreme. Refuges to thermally induced coral bleaching may include sites where extreme, high-frequency thermal variability may select for coral holobionts preadapted to, and physiologically condition corals to withstand, regional increases in water temperature.J.C.B.S. was partially supported by Fundac¸a˜o para a Cieˆncia e a Tecnologia (project PEst-C/MAR/LA0015/2011) and by the European Regional Development Fund through the Operational Competitiveness Programme (National Strategic Reference Framework). Kristen Davis was partially supported by a Woods Hole Oceanographic Institution postdoctoral scholarship. This research was supported by KAUST with awards USA 00002 and KSA 00011

An interdisciplinary mixed-methods approach to developing antimicrobial stewardship interventions:Protocol for the preserving antibiotics through safe stewardship (PASS) research programme [version 1; peer review: 2 approved]

Behaviour change is key to combating antimicrobial resistance. Antimicrobial stewardship (AMS) programmes promote and monitor judicious antibiotic use, but there is little consideration of behavioural and social influences when designing interventions. We outline a programme of research which aims to co-design AMS interventions across healthcare settings, by integrating data-science, evidence- synthesis, behavioural-science and user-centred design. The project includes three work-packages (WP): WP1 (Identifying patterns of prescribing): analysis of electronic health-records to identify prescribing patterns in care-homes, primary-care, and secondary-care. An online survey will investigate consulting/antibiotic-seeking behaviours in members of the public. WP2 (Barriers and enablers to prescribing in practice): Semi-structured interviews and observations of practice to identify barriers/enablers to prescribing, influences on antibiotic-seeking behaviour and the social/contextual factors underpinning prescribing. Systematic reviews of AMS interventions to identify the components of existing interventions associated with effectiveness. Design workshops to identify constraints influencing the form of the intervention. Interviews conducted with healthcare-professionals in community pharmacies, care-homes, primary-, and secondary-care and with members of the public. Topic guides and analysis based on the Theoretical Domains Framework. Observations conducted in care-homes, primary and secondary-care with analysis drawing on grounded theory. Systematic reviews of interventions in each setting will be conducted, and interventions described using the Behaviour Change Technique taxonomy v1. Design workshops in care-homes, primary-, and secondary care. WP3 (Co-production of interventions and dissemination). Findings will be integrated to identify opportunities for interventions, and assess whether existing interventions target influences on antibiotic use. Stakeholder panels will be assembled to co-design and refine interventions in each setting, applying the Affordability, Practicability, Effectiveness, Acceptability, Side-effects and Equity (APEASE) criteria to prioritise candidate interventions. Outputs will inform development of new AMS interventions and/or optimisation of existing interventions. We will also develop web-resources for stakeholders providing analyses of antibiotic prescribing patterns, prescribing behaviours, and evidence reviews

A Qualitative Exploration of Patient and Staff Experiences of the Receipt and Delivery of Specialist Weight Management Services in the UK

Background Addressing the increasing prevalence of obesity is a global public health priority. Severe obesity (body mass index > 40) reduces life expectancy, due to its association with people developing complications (e.g. diabetes, cancer, cardiovascular disease), and greatly impairs quality of life. The National Health Service (NHS) in the UK provides specialist weight management services (SWMS) for people with severe obesity, but key uncertainties remain around patient access to and engagement with weight management services, as well as pathways beyond the service. Methods In this multiple methods study, using online forum data and semi-structured interviews, stakeholders’ experiences of delivering and receiving SWMS were explored. Using the web search engine Google with keywords and web address (URL) identifiers, relevant public online platforms were sourced with snowball sampling and search strings used to identify threads related to people’s experiences of accessing SWMS (n = 57). Interviews were conducted with 24 participants (nine patients, 15 staff), and data from all sources were analysed thematically using the framework approach. Results Six themes related to access to and engagement with SWMS emerged during data analysis: (1) making the first move, (2) uncertainty and confusion, (3) resource issues, (4) respect and understanding, (5) mode of delivery, and (6) desire for ongoing support. Conclusion There is a mixed and varied picture of SWMS provision across the UK. The service offered is based on local clinical decision making and available resources, resulting in a range of patient experiences and perspectives. Whilst service capacity issues and patient anxiety were seen as barriers to accessing care, peer support and positive clinical and group interactions (connectedness between individuals) were considered to increase engagement

Patient experience and reflective learning (PEARL): a mixed methods protocol for staff insight development in acute and intensive care medicine in the UK

INTRODUCTION: Patient and staff experiences are strongly influenced by attitudes and behaviours, and provide important insights into care quality. Patient and staff feedback could be used more effectively to enhance behaviours and improve care through systematic integration with techniques for reflective learning. We aim to develop a reflective learning framework and toolkit for healthcare staff to improve patient, family and staff experience. METHODS & ANALYSIS: Local project teams including staff and patients from the acute medical units (AMUs) and intensive care units (ICUs) of three National Health Service trusts will implement two experience surveys derived from existing instruments: a continuous patient and relative survey and an annual staff survey. Survey data will be supplemented by ethnographic interviews and observations in the workplace to evaluate barriers to and facilitators of reflective learning. Using facilitated iterative co-design, local project teams will supplement survey data with their experiences of healthcare to identify events, actions, activities and interventions which promote personal insight and empathy through reflective learning. Outputs will be collated by the central project team to develop a reflective learning framework and toolkit which will be fed back to the local groups for review, refinement and piloting. The development process will be mapped to a conceptual theory of reflective learning which combines psychological and pedagogical theories of learning, alongside theories of behaviour change based on capability, opportunity and motivation influencing behaviour. The output will be a locally-adaptable workplace-based toolkit providing guidance on using reflective learning to incorporate patient and staff experience in routine clinical activities. ETHICS & DISSEMINATION: The PEARL project has received ethics approval from the London Brent Research Ethics Committee (REC Ref 16/LO/224). We propose a national cluster randomised step-wedge trial of the toolkit developed for large-scale evaluation of impact on patient outcomes

How can an understanding of plant-pollinator interactions contribute to global food security?

Pollination of crops by animals is an essential part of global food production, but evidence suggests that wild pollinator populations may be declining while a number of problems are besetting managed honey bee colonies. Animal-pollinated crops grown today, bred in an environment where pollination was less likely to limit fruit set, are often suboptimal in attracting and sustaining their pollinator populations. Research into plant-pollinator interactions is often conducted in a curiosity-driven, ecological framework, but may inform breeding and biotechnological approaches to enhance pollinator attraction and crop yield. In this article we review key topics in current plant-pollinator research that have potential roles in future crop breeding for enhanced global food security

Incidence, healthcare-seeking behaviours, antibiotic use and natural history of common infection syndromes in England:results from the Bug Watch community cohort study

Background: Better information on the typical course and management of acute common infections in the community could inform antibiotic stewardship campaigns. We aimed to investigate the incidence, management, and natural history of a range of infection syndromes (respiratory, gastrointestinal, mouth/dental, skin/soft tissue, urinary tract, and eye). Methods: Bug Watch was an online prospective community cohort study of the general population in England (2018–2019) with weekly symptom reporting for 6 months. We combined symptom reports into infection syndromes, calculated incidence rates, described the proportion leading to healthcare-seeking behaviours and antibiotic use, and estimated duration and severity. Results: The cohort comprised 873 individuals with 23,111 person-weeks follow-up. The mean age was 54 years and 528 (60%) were female. We identified 1422 infection syndromes, comprising 40,590 symptom reports. The incidence of respiratory tract infection syndromes was two per person year; for all other categories it was less than one. 194/1422 (14%) syndromes led to GP (or dentist) consultation and 136/1422 (10%) to antibiotic use. Symptoms usually resolved within a week and the third day was the most severe. Conclusions: Most people reported managing their symptoms without medical consultation. Interventions encouraging safe self-management across a range of acute infection syndromes could decrease pressure on primary healthcare services and support targets for reducing antibiotic prescribing

Adjunctive rifampicin for Staphylococcus aureus bacteraemia (ARREST): a multicentre, randomised, double-blind, placebo-controlled trial.

BACKGROUND: Staphylococcus aureus bacteraemia is a common cause of severe community-acquired and hospital-acquired infection worldwide. We tested the hypothesis that adjunctive rifampicin would reduce bacteriologically confirmed treatment failure or disease recurrence, or death, by enhancing early S aureus killing, sterilising infected foci and blood faster, and reducing risks of dissemination and metastatic infection. METHODS: In this multicentre, randomised, double-blind, placebo-controlled trial, adults (≥18 years) with S aureus bacteraemia who had received ≤96 h of active antibiotic therapy were recruited from 29 UK hospitals. Patients were randomly assigned (1:1) via a computer-generated sequential randomisation list to receive 2 weeks of adjunctive rifampicin (600 mg or 900 mg per day according to weight, oral or intravenous) versus identical placebo, together with standard antibiotic therapy. Randomisation was stratified by centre. Patients, investigators, and those caring for the patients were masked to group allocation. The primary outcome was time to bacteriologically confirmed treatment failure or disease recurrence, or death (all-cause), from randomisation to 12 weeks, adjudicated by an independent review committee masked to the treatment. Analysis was intention to treat. This trial was registered, number ISRCTN37666216, and is closed to new participants. FINDINGS: Between Dec 10, 2012, and Oct 25, 2016, 758 eligible participants were randomly assigned: 370 to rifampicin and 388 to placebo. 485 (64%) participants had community-acquired S aureus infections, and 132 (17%) had nosocomial S aureus infections. 47 (6%) had meticillin-resistant infections. 301 (40%) participants had an initial deep infection focus. Standard antibiotics were given for 29 (IQR 18-45) days; 619 (82%) participants received flucloxacillin. By week 12, 62 (17%) of participants who received rifampicin versus 71 (18%) who received placebo experienced treatment failure or disease recurrence, or died (absolute risk difference -1·4%, 95% CI -7·0 to 4·3; hazard ratio 0·96, 0·68-1·35, p=0·81). From randomisation to 12 weeks, no evidence of differences in serious (p=0·17) or grade 3-4 (p=0·36) adverse events were observed; however, 63 (17%) participants in the rifampicin group versus 39 (10%) in the placebo group had antibiotic or trial drug-modifying adverse events (p=0·004), and 24 (6%) versus six (2%) had drug interactions (p=0·0005). INTERPRETATION: Adjunctive rifampicin provided no overall benefit over standard antibiotic therapy in adults with S aureus bacteraemia. FUNDING: UK National Institute for Health Research Health Technology Assessment

Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK.

BACKGROUND: A safe and efficacious vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), if deployed with high coverage, could contribute to the control of the COVID-19 pandemic. We evaluated the safety and efficacy of the ChAdOx1 nCoV-19 vaccine in a pooled interim analysis of four trials. METHODS: This analysis includes data from four ongoing blinded, randomised, controlled trials done across the UK, Brazil, and South Africa. Participants aged 18 years and older were randomly assigned (1:1) to ChAdOx1 nCoV-19 vaccine or control (meningococcal group A, C, W, and Y conjugate vaccine or saline). Participants in the ChAdOx1 nCoV-19 group received two doses containing 5 × 1010 viral particles (standard dose; SD/SD cohort); a subset in the UK trial received a half dose as their first dose (low dose) and a standard dose as their second dose (LD/SD cohort). The primary efficacy analysis included symptomatic COVID-19 in seronegative participants with a nucleic acid amplification test-positive swab more than 14 days after a second dose of vaccine. Participants were analysed according to treatment received, with data cutoff on Nov 4, 2020. Vaccine efficacy was calculated as 1 - relative risk derived from a robust Poisson regression model adjusted for age. Studies are registered at ISRCTN89951424 and ClinicalTrials.gov, NCT04324606, NCT04400838, and NCT04444674. FINDINGS: Between April 23 and Nov 4, 2020, 23 848 participants were enrolled and 11 636 participants (7548 in the UK, 4088 in Brazil) were included in the interim primary efficacy analysis. In participants who received two standard doses, vaccine efficacy was 62·1% (95% CI 41·0-75·7; 27 [0·6%] of 4440 in the ChAdOx1 nCoV-19 group vs71 [1·6%] of 4455 in the control group) and in participants who received a low dose followed by a standard dose, efficacy was 90·0% (67·4-97·0; three [0·2%] of 1367 vs 30 [2·2%] of 1374; pinteraction=0·010). Overall vaccine efficacy across both groups was 70·4% (95·8% CI 54·8-80·6; 30 [0·5%] of 5807 vs 101 [1·7%] of 5829). From 21 days after the first dose, there were ten cases hospitalised for COVID-19, all in the control arm; two were classified as severe COVID-19, including one death. There were 74 341 person-months of safety follow-up (median 3·4 months, IQR 1·3-4·8): 175 severe adverse events occurred in 168 participants, 84 events in the ChAdOx1 nCoV-19 group and 91 in the control group. Three events were classified as possibly related to a vaccine: one in the ChAdOx1 nCoV-19 group, one in the control group, and one in a participant who remains masked to group allocation. INTERPRETATION: ChAdOx1 nCoV-19 has an acceptable safety profile and has been found to be efficacious against symptomatic COVID-19 in this interim analysis of ongoing clinical trials. FUNDING: UK Research and Innovation, National Institutes for Health Research (NIHR), Coalition for Epidemic Preparedness Innovations, Bill & Melinda Gates Foundation, Lemann Foundation, Rede D'Or, Brava and Telles Foundation, NIHR Oxford Biomedical Research Centre, Thames Valley and South Midland's NIHR Clinical Research Network, and AstraZeneca