Higher Education outreach to widen participation: toolkits for practitioners. Overview

The toolkits are a distillation of the learning, methods and resources developed by Aimhigher and the Lifelong Learning Network programmes to support the effective strategy, management and delivery of outreach work to encourage progression to higher education for under-represented groups. The toolkits recontextualise the learning from these programmes to fit the current higher education environment. The toolkits form a suite of four (see links to right). They include: • Toolkit 1 Partnership • Toolkit 2 Targeting • Toolkit 3 Programmes • Toolkit 4 Evaluation • Resources and glossary.This is the second and updated edition, the first edition of the Toolkits was published in December 2012.Higher Education Funding Council for England (HEFCE

Basic science232. Certolizumab pegol prevents pro-inflammatory alterations in endothelial cell function

Background: Cardiovascular disease is a major comorbidity of rheumatoid arthritis (RA) and a leading cause of death. Chronic systemic inflammation involving tumour necrosis factor alpha (TNF) could contribute to endothelial activation and atherogenesis. A number of anti-TNF therapies are in current use for the treatment of RA, including certolizumab pegol (CZP), (Cimzia ®; UCB, Belgium). Anti-TNF therapy has been associated with reduced clinical cardiovascular disease risk and ameliorated vascular function in RA patients. However, the specific effects of TNF inhibitors on endothelial cell function are largely unknown. Our aim was to investigate the mechanisms underpinning CZP effects on TNF-activated human endothelial cells. Methods: Human aortic endothelial cells (HAoECs) were cultured in vitro and exposed to a) TNF alone, b) TNF plus CZP, or c) neither agent. Microarray analysis was used to examine the transcriptional profile of cells treated for 6 hrs and quantitative polymerase chain reaction (qPCR) analysed gene expression at 1, 3, 6 and 24 hrs. NF-κB localization and IκB degradation were investigated using immunocytochemistry, high content analysis and western blotting. Flow cytometry was conducted to detect microparticle release from HAoECs. Results: Transcriptional profiling revealed that while TNF alone had strong effects on endothelial gene expression, TNF and CZP in combination produced a global gene expression pattern similar to untreated control. The two most highly up-regulated genes in response to TNF treatment were adhesion molecules E-selectin and VCAM-1 (q 0.2 compared to control; p > 0.05 compared to TNF alone). The NF-κB pathway was confirmed as a downstream target of TNF-induced HAoEC activation, via nuclear translocation of NF-κB and degradation of IκB, effects which were abolished by treatment with CZP. In addition, flow cytometry detected an increased production of endothelial microparticles in TNF-activated HAoECs, which was prevented by treatment with CZP. Conclusions: We have found at a cellular level that a clinically available TNF inhibitor, CZP reduces the expression of adhesion molecule expression, and prevents TNF-induced activation of the NF-κB pathway. Furthermore, CZP prevents the production of microparticles by activated endothelial cells. This could be central to the prevention of inflammatory environments underlying these conditions and measurement of microparticles has potential as a novel prognostic marker for future cardiovascular events in this patient group. Disclosure statement: Y.A. received a research grant from UCB. I.B. received a research grant from UCB. S.H. received a research grant from UCB. All other authors have declared no conflicts of interes

Metrics for optimising the multi-dimensional value of resources recovered from waste in a circular economy: A critical review

© 2017 The Authors - Established assessment methods focusing on resource recovery from waste within a circular economy context consider few or even a single domain/s of value, i.e. environmental, economic, social and technical domains. This partial approach often delivers misleading messages for policy- and decision-makers. It fails to accurately represent systems complexity, and obscures impacts, trade-offs and problem shifting that resource recovery processes or systems intended to promote circular economy may cause. Here, we challenge such partial approaches by critically reviewing the existing suite of environmental, economic, social and technical metrics that have been regularly observed and used in waste management and resource recovery systems' assessment studies, upstream and downstream of the point where waste is generated. We assess the potential of those metrics to evaluate ‘complex value’ of materials, components and products, i.e., the holistic sum of their environmental, economic, social and technical benefits and impacts across the system. Findings suggest that the way resource recovery systems are assessed and evaluated require simplicity, yet must retain a suitable minimum level of detail across all domains of value, which is pivotal for enabling sound decision-making processes. Criteria for defining a suitable set of metrics for assessing resource recovery from waste require them to be simple, transparent and easy to measure, and be both system- and stakeholder-specific. Future developments must focus on providing a framework for the selection of metrics that accurately describe (or at least reliably proxy for) benefits and impacts across all domains of value, enabling effective and transparent analysis of resource recovery form waste in circular economy systems.We gratefully acknowledge support of the UK Natural Environ-ment Research Council (NERC) and the UK Economic and SocialResearch Council (ESRC) who funded this work in the context of‘Complex Value Optimisation for Resource Recovery’(CVORR)project (Grant No. NE/L014149/1)

Genomic epidemiology of SARS-CoV-2 in a UK university identifies dynamics of transmission

AbstractUnderstanding SARS-CoV-2 transmission in higher education settings is important to limit spread between students, and into at-risk populations. In this study, we sequenced 482 SARS-CoV-2 isolates from the University of Cambridge from 5 October to 6 December 2020. We perform a detailed phylogenetic comparison with 972 isolates from the surrounding community, complemented with epidemiological and contact tracing data, to determine transmission dynamics. We observe limited viral introductions into the university; the majority of student cases were linked to a single genetic cluster, likely following social gatherings at a venue outside the university. We identify considerable onward transmission associated with student accommodation and courses; this was effectively contained using local infection control measures and following a national lockdown. Transmission clusters were largely segregated within the university or the community. Our study highlights key determinants of SARS-CoV-2 transmission and effective interventions in a higher education setting that will inform public health policy during pandemics.</jats:p

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Higher Education outreach to widen participation: toolkits for practitioners. Partnership.

The toolkits are a distillation of the learning, methods and resources developed by Aimhigher and the Lifelong Learning Network programmes to support the effective strategy, management and delivery of outreach work to encourage progression to higher education for under-represented groups. The toolkits recontextualise the learning from these programmes to fit the current higher education environment. The toolkits form a suite of four.They include: • Toolkit 1 Partnership • Toolkit 2 Targeting • Toolkit 3 Programmes • Toolkit 4 Evaluation • Resources and glossary.This is the second and updated edition, the first edition of the Toolkits was published in December 2012.Higher Education Funding Council for England (HEFCE