What types of science count? Exploring the formal, informal and hidden curricula in undergraduate medical education, with a particular focus on beliefs about science and knowledge.

Background and Purpose. This PhD thesis is a qualitative research project using interpretive and socio-cultural theories in a case study design. It explores medical students’ beliefs about scientific knowledge and the nature of evidence as applied to medicine, at key transition points in their education. This thesis situates current theories and conceptual models of epistemological development from the fields of psychology and education within the emergent field of medical education. Its aim is to provide insights into personal epistemological development, any curriculum barriers to such and provide insights into how students can be better supported, notably in transition periods. It addresses both a gap in the literature and the calls for more research into the development of student epistemologies in professional education. The thesis key research questions are: • What are medical students’ beliefs and understandings about the nature of scientific knowledge as applied to medicine? • What curriculum factors appear to facilitate or inhibit medical students’ epistemological development, at key transitions? Methodology. The case study design involved a four phase approach; • Phase 1: This was a critical discourse analysis of key policy and curricula texts to explore assumptions, inconsistencies or disputes relating to science and scientific content in the field of medical education. • Phase 2: This was the observation of learning episodes in preparation for Phase 3 involving participants. The purpose of Phase 2 was to situate and ground conversations with participants in real experiences. • Phase 3: This phase involved task groups and semi-structured interviews with medical students and faculty participants based at the University of Exeter Medical School (UEMS). Task groups and semi-structured interviews explored individual beliefs about the nature of science and scientific evidence as applied to medicine generally and the Bachelor of Medicine, Bachelor of Surgery (BMBS) curriculum content specifically. This included its contested scientific content and the nature of complexity and uncertainty in evidence based medicine. • Phase 4: This final phase involved presenting the case study findings to two other UK medical schools to explore the tentative applicability or transferability. The purpose of Phase 4 was to consider how case-specific and context bound the case study findings are. Findings. Findings suggest there is substantial variation in how medical students and faculty talk about science and evidence in medicine. This is influenced by their experiences of courses studied prior to entering medical school and their maturity in age. Medical students described how faculty informally spoke about the ambiguity within medical practice as clinical decision making, but there were very few reports of faculty explicitly speaking about the uncertain and tentative nature of scientific knowledge underpinning applied medicine. The bio-sciences were still dominant in terms of curriculum and assessment content. Where science in medicine is defined and approaches to scientific research are stated, formal curriculum documents espouse a narrow and positivistic methodological approach, which serves to perpetuate misconceptions regarding scientific research within medicine and may influence epistemological beliefs about the nature of science within medicine. Discussion and Conclusions. It is anticipated this case study will afford medical educators and curriculum designers insights upon which to address imbalances, include appropriate content, and reinforce good practice, so that medical graduates are effectively prepared for the challenges of a career in medicine

Stratified analyses refine association between TLR7 rare variants and severe COVID-19

Summary: Despite extensive global research into genetic predisposition for severe COVID-19, knowledge on the role of rare host genetic variants and their relation to other risk factors remains limited. Here, 52 genes with prior etiological evidence were sequenced in 1,772 severe COVID-19 cases and 5,347 population-based controls from Spain/Italy. Rare deleterious TLR7 variants were present in 2.4% of young (<60 years) cases with no reported clinical risk factors (n = 378), compared to 0.24% of controls (odds ratio [OR] = 12.3, p = 1.27 × 10−10). Incorporation of the results of either functional assays or protein modeling led to a pronounced increase in effect size (ORmax = 46.5, p = 1.74 × 10−15). Association signals for the X-chromosomal gene TLR7 were also detected in the female-only subgroup, suggesting the existence of additional mechanisms beyond X-linked recessive inheritance in males. Additionally, supporting evidence was generated for a contribution to severe COVID-19 of the previously implicated genes IFNAR2, IFIH1, and TBK1. Our results refine the genetic contribution of rare TLR7 variants to severe COVID-19 and strengthen evidence for the etiological relevance of genes in the interferon signaling pathway