Critical illness in COVID-19 is an extreme and clinically homogeneous disease phenotype that we have previously shown1 to be highly efficient for discovery of genetic associations2. Despite the advanced stage of illness at presentation, we have shown that host genetics in patients who are critically ill with COVID-19 can identify immunomodulatory therapies with strong beneficial effects in this group3. Here we analyse 24,202 cases of COVID-19 with critical illness comprising a combination of microarray genotype and whole-genome sequencing data from cases of critical illness in the international GenOMICC (11,440 cases) study, combined with other studies recruiting hospitalized patients with a strong focus on severe and critical disease: ISARIC4C (676 cases) and the SCOURGE consortium (5,934 cases). To put these results in the context of existing work, we conduct a meta-analysis of the new GenOMICC genome-wide association study (GWAS) results with previously published data. We find 49 genome-wide significant associations, of which 16 have not been reported previously. To investigate the therapeutic implications of these findings, we infer the structural consequences of protein-coding variants, and combine our GWAS results with gene expression data using a monocyte transcriptome-wide association study (TWAS) model, as well as gene and protein expression using Mendelian randomization. We identify potentially druggable targets in multiple systems, including inflammatory signalling (JAK1), monocyte–macrophage activation and endothelial permeability (PDE4A), immunometabolism (SLC2A5 and AK5), and host factors required for viral entry and replication (TMPRSS2 and RAB2A).

This article compares and contrasts two versions of the Education Endowment Foundation's (EEF) Teaching and Learning Toolkit (‘Toolkit’), a web‐based summary of international evidence on teaching 3–18 year‐olds. The Toolkit has localised versions in six different languages in Australia, Cameroon, Chile, Jordan and Spain. The initial Toolkit, created in 2011 with funding from the Sutton Trust and updated since then with funding from EEF, drew upon over 250 meta‐analyses across 30 areas of education research. An updated version, drawing on a database of over 2500 single studies from these meta‐analyses was launched in Autumn 2021. This change was motivated by increased interest in evidence‐use in education, and a desire to engage in more rigorous synthesis of primary studies. The article presents the rationale for these changes, outlines the methods adopted to populate and analyse the Toolkit database and presents results from this analysis. Findings indicate that although the broad picture of the relative benefits of the different approaches is similar, a more fine‐grained analysis is possible. This deeper synthesis can provide more specific guidance about what has been successful in the different areas of the Toolkit in research studies and offers opportunities for further refinement and improvement. This increased specificity, however, comes at the cost of greater complexity in the findings and the implications for policy and practice, and it increases the challenge of ensuring findings are both accurate and accessible. A final section reflects on the challenges of summarising evidence from research to inform decision‐making in education.

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2017) 'Educatorstudent communication in sex relationship education : a comparison of teacher and peer-led interventions.', Pastoral care in education., 35 (4). pp. 267-283.The full-text may be used and/or reproduced, and given to third parties in any format or medium, without prior permission or charge, for personal research or study, educational, or not-for-prot purposes provided that:• a full bibliographic reference is made to the original source • a link is made to the metadata record in DRO • the full-text is not changed in any way The full-text must not be sold in any format or medium without the formal permission of the copyright holders.Please consult the full DRO policy for further details. ABSTRACTThis paper presents findings from a comparative study of peer-and teacher-led Sex and Relationship Education (SRE). One lesson delivered by a peer educator, and one lesson delivered by a teacher was observed with the aim of exploring the communicative process between educators and students within SRE. It is claimed that open communication between students and peer educators promotes the adoption of positive attitudes to sexual health, making it a potential alternative to teacher-led provision. Yet to our knowledge, no studies have investigated the communicative process within peer-led adolescent health interventions to examine factors underpinning its potential efficacy. The development of a coding scheme to measure the extent to which educators and students are communicating openly within SRE is used to describe the communicative process between sex educators and students, characterise differences in communication within peer and teacher-led conditions and discuss how these differences affect student participation in SRE. Results suggest interaction of students in the peer-led condition was different to that of students receiving teacher-led SRE; and provide valuable insight into educator-student communication in the context of classroom-based SRE.

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