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 paper describes a systematic review of international research evidence identifying the most promising approaches to attracting and retaining teachers in hard-to-staff areas. Only empirical studies that employed a causal or suitable comparative design and had robust measurements of recruitment and retention outcomes were considered. Studies were assessed for strength of evidence taking into account threats to trustworthiness which may bias the results. A search of 13 electronic databases and Google/Google scholar identified 20 distinct research reports that met the inclusion criteria. Financial incentives was the only approach that seemsto work in attracting teachers to challenging schools, but not effective in retaining them. To keep teachers working in challenging schools a supportive and conducive working environment would be needed. Other approaches such as mentoring, support, or teacher development do not have strong evidence of effectiveness, largely because much of the research on these approaches was weak. More robust research capable of addressing causal questions is therefore urgently required to determine their impact in attracting and retaining good teachers in areas where they are most needed. Long-term solution would be to change schoolallocation policies and improve economic conditions in such areas so that the problem of staffing does not arise.
Feedback is an integral part of education and there is a substantial body of trials exploring and confirming its effect on learning. This evidence base comes mostly from studies of compulsory school age children; there is very little evidence to support effective feedback practice at higher education, beyond the frameworks and strategies advocated by those claiming expertise in the area. This systematic review aims to address this gap. We review causal evidence from trials of feedback and formative assessment in higher education. Although the evidence base is currently limited, our results suggest that low stakes‐quizzing is a particularly powerful approach and that there are benefits for forms of peer and tutor feedback, although these depend on implementation factors. There was mixed evidence for praise, grading and technology‐based feedback. We organise our findings into several evidence‐grounded categories and discuss the next steps for the field and evidence‐informed feedback practice in universities.
Background: A raft of initiatives and reforms have been introduced in many countries to attract and recruit school teachers, many of which do not have a clear evidence base, so their effectiveness remains unclear. Prior research has been largely correlational in design. This paper describes a rigorous and comprehensive review of international evidence, synthesising the findings of some of the strongest empirical work so far. Methods: The review synthesises a total of 120 pieces of research from 13 electronic databases, Google/Google scholar and other sources. Each study is weighted by strength of evidence. Results: The strongest evidence suggests that targeted money can encourage people into teaching but does not necessarily keep them in the teaching profession. The money needs to be large enough to compensate for the disadvantages of working in certain schools and areas, and competitive enough to offset the opportunity costs of not being in more lucrative occupations, and its effect is only short-term. Conclusions: Continuing professional development (CPD) and early career support could be promising approaches for retaining teachers in the profession, but the evidence for them is weak. There is no evidence that any other approaches work, largely because of the lack of robust studies.
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