Clinical and clinicopathological features and outcomes of cats with suspected dietary induced pancytopenia

Background: After a strong epidemiological link to diet was established in an outbreak of pancytopenia in cats in spring 2021 in the United Kingdom, 3 dry diets were recalled. Concentrations of the hemato- and myelotoxic mycotoxins T-2, HT-2 and diacetoxyscirpenol (DAS) greater than the European Commission guidance for dry cat foods were detected in the recalled diets. Objectives: To describe clinical and clinicopathological findings in cats diagnosed with suspected diet induced pancytopenia. Animals: Fifty cats presenting with pancytopenia after exposure to a recalled diet. Methods: Multicenter retrospective case series study. Cats with known exposure to 1 of the recalled diets were included if presented with bi- or pancytopenia and underwent bone marrow examination. Results: Case fatality rate was 78%. Bone marrow aspirates and biopsy examination results were available in 23 cats; 19 cats had a bone marrow aspirate, and 8 cats had a biopsy core, available for examination. Bone marrow hypo to aplasia—often affecting all cell lines—was the main feature in all 31 available core specimens. A disproportionately pronounced effect on myeloid and megakaryocytic cells was observed in 19 cats. Myelofibrosis or bone marrow necrosis was not a feature. Conclusion and Clinical Importance: Mycotoxin induced pancytopenia should be considered as differential diagnosis in otherwise healthy cats presenting with bi- or pancytopenia and bone marrow hypo- to aplasia

International genome-wide meta-analysis identifies new primary biliary cirrhosis risk loci and targetable pathogenic pathways.

Primary biliary cirrhosis (PBC) is a classical autoimmune liver disease for which effective immunomodulatory therapy is lacking. Here we perform meta-analyses of discovery data sets from genome-wide association studies of European subjects (n=2,764 cases and 10,475 controls) followed by validation genotyping in an independent cohort (n=3,716 cases and 4,261 controls). We discover and validate six previously unknown risk loci for PBC (Pcombined<5 × 10(-8)) and used pathway analysis to identify JAK-STAT/IL12/IL27 signalling and cytokine-cytokine pathways, for which relevant therapies exist

Exploring UK medical school differences: the MedDifs study of selection, teaching, student and F1 perceptions, postgraduate outcomes and fitness to practise.

BACKGROUND: Medical schools differ, particularly in their teaching, but it is unclear whether such differences matter, although influential claims are often made. The Medical School Differences (MedDifs) study brings together a wide range of measures of UK medical schools, including postgraduate performance, fitness to practise issues, specialty choice, preparedness, satisfaction, teaching styles, entry criteria and institutional factors. METHOD: Aggregated data were collected for 50 measures across 29 UK medical schools. Data include institutional history (e.g. rate of production of hospital and GP specialists in the past), curricular influences (e.g. PBL schools, spend per student, staff-student ratio), selection measures (e.g. entry grades), teaching and assessment (e.g. traditional vs PBL, specialty teaching, self-regulated learning), student satisfaction, Foundation selection scores, Foundation satisfaction, postgraduate examination performance and fitness to practise (postgraduate progression, GMC sanctions). Six specialties (General Practice, Psychiatry, Anaesthetics, Obstetrics and Gynaecology, Internal Medicine, Surgery) were examined in more detail. RESULTS: Medical school differences are stable across time (median alpha = 0.835). The 50 measures were highly correlated, 395 (32.2%) of 1225 correlations being significant with p < 0.05, and 201 (16.4%) reached a Tukey-adjusted criterion of p < 0.0025. Problem-based learning (PBL) schools differ on many measures, including lower performance on postgraduate assessments. While these are in part explained by lower entry grades, a surprising finding is that schools such as PBL schools which reported greater student satisfaction with feedback also showed lower performance at postgraduate examinations. More medical school teaching of psychiatry, surgery and anaesthetics did not result in more specialist trainees. Schools that taught more general practice did have more graduates entering GP training, but those graduates performed less well in MRCGP examinations, the negative correlation resulting from numbers of GP trainees and exam outcomes being affected both by non-traditional teaching and by greater historical production of GPs. Postgraduate exam outcomes were also higher in schools with more self-regulated learning, but lower in larger medical schools. A path model for 29 measures found a complex causal nexus, most measures causing or being caused by other measures. Postgraduate exam performance was influenced by earlier attainment, at entry to Foundation and entry to medical school (the so-called academic backbone), and by self-regulated learning. Foundation measures of satisfaction, including preparedness, had no subsequent influence on outcomes. Fitness to practise issues were more frequent in schools producing more male graduates and more GPs. CONCLUSIONS: Medical schools differ in large numbers of ways that are causally interconnected. Differences between schools in postgraduate examination performance, training problems and GMC sanctions have important implications for the quality of patient care and patient safety

The Analysis of Teaching of Medical Schools (AToMS) survey: an analysis of 47,258 timetabled teaching events in 25 UK medical schools relating to timing, duration, teaching formats, teaching content, and problem-based learning.

BACKGROUND: What subjects UK medical schools teach, what ways they teach subjects, and how much they teach those subjects is unclear. Whether teaching differences matter is a separate, important question. This study provides a detailed picture of timetabled undergraduate teaching activity at 25 UK medical schools, particularly in relation to problem-based learning (PBL). METHOD: The Analysis of Teaching of Medical Schools (AToMS) survey used detailed timetables provided by 25 schools with standard 5-year courses. Timetabled teaching events were coded in terms of course year, duration, teaching format, and teaching content. Ten schools used PBL. Teaching times from timetables were validated against two other studies that had assessed GP teaching and lecture, seminar, and tutorial times. RESULTS: A total of 47,258 timetabled teaching events in the academic year 2014/2015 were analysed, including SSCs (student-selected components) and elective studies. A typical UK medical student receives 3960 timetabled hours of teaching during their 5-year course. There was a clear difference between the initial 2 years which mostly contained basic medical science content and the later 3 years which mostly consisted of clinical teaching, although some clinical teaching occurs in the first 2 years. Medical schools differed in duration, format, and content of teaching. Two main factors underlay most of the variation between schools, Traditional vs PBL teaching and Structured vs Unstructured teaching. A curriculum map comparing medical schools was constructed using those factors. PBL schools differed on a number of measures, having more PBL teaching time, fewer lectures, more GP teaching, less surgery, less formal teaching of basic science, and more sessions with unspecified content. DISCUSSION: UK medical schools differ in both format and content of teaching. PBL and non-PBL schools clearly differ, albeit with substantial variation within groups, and overlap in the middle. The important question of whether differences in teaching matter in terms of outcomes is analysed in a companion study (MedDifs) which examines how teaching differences relate to university infrastructure, entry requirements, student perceptions, and outcomes in Foundation Programme and postgraduate training

Early immunological development and mortality from infectious disease in later life.

In rural Gambia the risk of mainly infection-related mortality is 10-fold higher for adults born in the nutritionally-debilitating 'hungry' season, suggesting that immune function may be compromised by events early in life. The current programme of research focuses on the biological mechanisms underlying this hypothesis, exploring early-life environmental influences on immune development and the long-term functional consequences these influences may have. Results obtained to date show that thymus development during infancy is critically sensitive to environmental exposures, with smaller thymuses observed in the hungry season. Measurement of the frequency of T-cell receptor excision circles indicate that thymus function is also sensitive to seasonal influences, with further studies implicating variations in breast-milk IL-7 as a possible mediator of these effects. Studies in adults have shown that size at birth is positively correlated with antibody responses to vaccination with polysaccharide antigens, thus providing evidence for long-term functional deficits. The present paper will review progress made to date within this field of research

Immune function in rural Gambian children is not related to season of birth, birth size, or maternal supplementation status.

BACKGROUND: We previously showed that mortality from infectious diseases among young adults in rural Gambia is strongly correlated with the season of their birth. This suggests that early life insults that involve fetal malnutrition, exposure to natural toxins, or highly seasonal infections affecting the infant or pregnant mother cause permanent damage to the immune system. Excess mortality begins after puberty and has a maximal odds ratio of >10 for deaths between ages 25 and 50 y. OBJECTIVE: We investigated the immune function of children according to birth weight, season of birth, and exposure to maternal dietary supplementation during pregnancy. DESIGN: Immune function was measured in 472 prepubertal children aged 6.5-9.5 y from 28 villages in rural Gambia. The mothers of these children had been randomly assigned to a high-energy prenatal supplementation program, which significantly increased birth weight. This permitted supplementation status, birth weight, and season of birth to be investigated as exposure variables. The outcome variables tested were naive responses to rabies and pneumococcus vaccines, delayed-type hypersensitivity skin reactions, and mucosal defense (secretory immunoglobulin A and dual-sugar permeability). RESULTS: Immune responses were strongly related to current age and sex, suggesting a high level of sensitivity, but were not consistently related to birth weight, season of birth, or maternal supplementation (control compared with intervention). CONCLUSION: Events in early life did not predict a measurable defect in immune response within this cohort of rural Gambian children. It is possible that the early programming of immune function may be mediated through a defect in immunologic memory or early senescence rather than through impairment of early responses

Structured elicitation of expert judgement in real-time eruption scenarios: an exercise for Piton de la Fournaise volcano, La Réunion island

co-auteur étrangerInternational audienceFormalised elicitation of expert judgements has been used to help tackle several problematic societal issues, including volcanic crises and pandemic threats. We present an expert elicitation exercise for Piton de la Fournaise volcano, La Réunion island, held remotely in April 2021. This involved 28 experts from nine countries who considered a hypothetical effusive eruption crisis involving a new vent opening in a high-risk area. The tele-elicitation presented several challenges, but is a promising and workable option for application to future volcanic crises. Our exercise considered an “uncommon” eruptive scenario with a vent outside the present caldera and within inhabited areas, and provided uncertainty ranges for several hazard-related questions for such a scenario (e.g. probability of eruption within a defined timeframe; elapsed time until lava flow reaches a critical location, and other hazard management issues). Our exercise indicated that such a scenario would probably present very different characteristics compared to recent eruptions, and that it is fundamental to include well-prepared expert elicitations in updated civil protection evacuation plans to improve disaster response procedures