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Conventional dendritic cells expressing the XCR1 chemokine receptor (cDC1s) excel at cross-presentation. Here, we developed and used a mouse model in which a Cre recombinase is expressed under the control of the Xcr1 gene while preserving XCR1 expression. We used it to generate mice with conditional deletion of MHC class II (MHCII) molecules on cDC1s. By preventing cDC1s to receive suppressive regulatory T cell inputs via MHCII-restricted interactions, the objective of the present study was to gauge whether MHCII-deficient cDC1s lose their capacity of tolerizing autoreactive CD8+ T cells. Whereas MHCII+ cDC1 readily cross-tolerized strongly autoreactive CD8+ T cells specific for a keratinocyte-derived self-antigen, MHCII-deficient cDC1s converted them into potent effectors capable of triggering a fast-onset lethal autoimmunity associated with severe skin histopathological manifestations. Preventing egress of such pathogenic self-reactive CD8+ T cell effectors from the cutaneous draining lymph nodes abrogated the autoimmune condition. Therefore, our results revealed that the cross-tolerizing capacity of cDC1s is not a property fully acquired at the time they undergo homeostatic maturation but needs to be enforced via MHCII-restricted, suppressive interactions with regulatory T cells. Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.The antibodies of jawless vertebrates consist of leucine-rich repeat arrays encoded by somatically assembled VLRB genes. It is unknown how the incomplete germline VLRB loci are converted into functional antibody genes during B lymphocyte development in lampreys. In Lampetra planeri larvae lacking the cytidine deaminase CDA2 gene, VLRB assembly fails, whereas the T lineage-associated VLRA and VLRC antigen receptor gene assemblies occur normally. Thus, CDA2 acts in a B cell lineage-specific fashion to support the somatic diversification of VLRB antibody genes. CDA2 is closely related to activation-induced cytidine deaminase (AID), which is essential for the elaboration of immunoglobulin gene repertoires in jawed vertebrates. Our results thus identify a convergent mechanism of antigen receptor gene assembly and diversification that independently evolved in the two sister branches of vertebrates. Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.AIMS This study explores the opinions and experiences of Irish Defences Forces' (IDF) graduates from University College Dublin's Diploma in Military Medicine Care (DMMC). It aims to identify which aspects of medical education are relevant for the development of military graduates in the role of Combat Medical Technician (CMT) in future. METHODS A validated Clinical Learning Environment Score tool was adapted and incorporated into an online survey. This was sent electronically to 71 graduates. Responses were anonymous. RESULTS 38 (54%) graduates responded. Student feedback was positive regarding teaching and clinical placements in the DMMC. In total 16 (42%) students reported use of their new skills in their daily work. Of the 9 (24%) deployed overseas, all used their new skills. Emergency and occupational health skills were used more frequently, while advanced skills were used rarely. CONCLUSION An increased emphasis on frequently used skills should be considered. Links to healthcare services would be of benefit to graduates in skills maintenance. Key advanced skills, such as intravenous cannulation and advanced airway management are rarely used but mechanisms to maintain them will improve the relevance of the programme to the CMT role. A change in how the IDF acknowledges qualifications may support more graduates in advancing and maintaining their career in the military medical workforce. © Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.INTRODUCTION A review of ballistic gelatin calibration standards has highlighted that data used from studies with different calibrations methods may not be able to be compared. Calibration of ballistic gelatin did not occur until the mid-1980s when Fackler recognised the deficiencies of uncalibrated gelatin. He determined that the calibration standard should be 85±5 mm of ball bearing penetration for a 180 m/s impact velocity. This study looks to improve on and optimise current ballistic gelatin calibration standards METHODS Nine 0.177 cal (4.5 mm) spheres were fired using a Daisy Powerline air rifle at velocities between 134 m/s and 224 m/s at 25 gelatin blocks (n=225). Velocities were measured using an Oehler Model 36 Chronograph with three Model 57 screens. Depth of penetration (DoP) was measured from the entry surface to the back end of the sphere via a Mitutoyo Absolute vernier calliper. RESULTS The R-squared regression model showed that all batches had a close fit to the regression line. Using the R-squared regression model, the equation y=0.584x - 20.02 (where x is the velocity) returned a DoP of 84.918 mm for a 180 m/s impact and therefore needed minimal adjustment to align with Fackler's 85 mm DoP. The equation can be adjusted to y=0.584x - 20.12 to return a DoP of 85 mm for 180 m/s. CONCLUSIONS We propose that the calibration standard of ballistic gelatin with 4.5 mm spheres is DoP=0.584x - 20.12 where DoP is the depth of penetration (mm) and x is the impact velocity (m/s), The measured DoP should be within 5% of the calculated DoP. © Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.Recent experience of humanitarian and disaster relief efforts have demonstrated the critical importance of the local health infrastructure and its response to a disaster in both the short and long term. With increasing involvement of Foreign Medical Teams (FMT), both military and civilian, in these relief efforts, there is a necessity to review how best a FMT can involve and develop the local response; it is no longer valid to design an intervention insular from the local population. Key themes found in interventions that have damaged the local infrastructure and response include bypassing, undermining and overstretching local capacities; poaching local staff; aid-fuelled inflation; lack of accountability; developing an intervention that the local population is incapable of providing once the FMT has gone and using the local infrastructure for service delivery for the FMT. Principles written by the Organisation for Economic Co-operation and Development summarise concepts that can be used when designing an intervention so as to avoid damaging the local response and their infrastructure. They focus on involving the local population, understanding the complexities and history of the area and the requirement to develop and instil resilience to future crises. © Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.BACKGROUND This article reports on the development and validation of a contextualised measure of personal resources for resilience in veterinary practice. METHODS Exploratory factor analysis and structural equation modelling were used to evaluate data from two surveys of veterinary practitioners. RESULTS Exploratory factor analysis of the first survey (n=300) revealed six items comprising the Veterinary Resilience Scale-Personal Resources (VRS-PR). These items focused on flexibility, adaptability, optimism, building strengths, enjoying challenges, and maintaining motivation and enthusiasm at work. Structural equation modelling using the second survey (n=744) confirmed the factor structure of the VRS-PR and established convergent validity with an established measure of general resilience, the Brief Resilience Scale. Examination of the mean and standard deviation of the combined survey data enabled scores on the VRS-PR to be provisionally classified into 'low', 'moderate' and 'high' (reported by approximately 13%, 72% and 15% of respondents, respectively). Respondents also reported results spanning 'low', 'moderate' and 'high' classifications for the Brief Resilience Scale (approximately 34%, 57% and 9%, respectively). CONCLUSION The VRS-PR may be used to evaluate the extent to which respondents draw upon the personal resources captured in the scale and identify areas for improvement. © British Veterinary Association 2020. No commercial re-use. See rights and permissions. Published by BMJ.BACKGROUND Canine parvovirus (CPV) represents one of the major infections in dogs. While supportive therapy significantly reduces mortality, other approaches have been reported to provide significant benefits. Unfortunately, the high cost of these treatments is typically a limiting factor. Consequently, a reliable prognostic tool allowing for an informed therapeutic approach would be of great interest. However, current methods are essentially based on 'a priori' selection of predictive variables, which could limit their predictive potential. METHODS In the present study, the predictive performances in terms of CPV enteritis survival likelihood of an operator-validated logistic regression were compared with those of more flexible methods featured by automatic variable selection. Several anamnestic, clinical, haematological and biochemical parameters were collected from 134 dogs at admission in a veterinary practice. Animal status was monitored until dismissal or death (mortality=21.6%). RESULTS The best automatic variable selection method (random forest) showed excellent discriminatory capabilities (AUC=0.997, sensitivity=0.941 and specificity=1) compared with the logistic regression model (AUC=0.831, sensitivity=0.882 and specificity=0.652), when evaluated on a fully independent test data set. The implemented approaches allowed to identify antithrombin, serum aspartate aminotransferase, serum lipase, monocyte and lymphocyte count as the clinical parameter combination with the highest predictive capability, thus limiting the panel of required tests. CONCLUSION The model validated in the present study allows prompt prediction of disease severity at admission and provides objective and reliable criteria to support the clinician in selection of the therapeutic approach. © British Veterinary Association 2020. No commercial re-use. See rights and permissions. Published by BMJ.BACKGROUND Teaching and learning how to perform examination of the ocular fundus is challenging. Smartphones can support to enhance students' confidence and experience. METHODS Following an optional year-4 ophthalmoscopy practical using hand-held ophthalmoscopes, students completed a questionnaire using a visual analogue scale (VAS) investigating if students felt smartphone use aided learning and if student's self-assessed confidence in visualising the ocular fundus had improved. VAS scores were compared using the Wilcoxon signed rank test (significance P less then 0.05). RESULTS All 30 year-4 students attending the practical participated to the study. Confidence in performing direct ophthalmoscopy significantly increased after the practical. Confidence after the practical was 65.3 (±19.8) per cent compared with before the practical when confidence was 20.1 (±15.6) per cent (P less then 0.001). The perceived usefulness of traditional teaching was 62.3 (±23.8) per cent. The perceived usefulness of the teaching with the smartphone was 91.
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