25 research outputs found
The impact of viral mutations on recognition by SARS-CoV-2 specific TÂ cells.
We identify amino acid variants within dominant SARS-CoV-2 T cell epitopes by interrogating global sequence data. Several variants within nucleocapsid and ORF3a epitopes have arisen independently in multiple lineages and result in loss of recognition by epitope-specific T cells assessed by IFN-γ and cytotoxic killing assays. Complete loss of T cell responsiveness was seen due to Q213K in the A∗01:01-restricted CD8+ ORF3a epitope FTSDYYQLY207-215; due to P13L, P13S, and P13T in the B∗27:05-restricted CD8+ nucleocapsid epitope QRNAPRITF9-17; and due to T362I and P365S in the A∗03:01/A∗11:01-restricted CD8+ nucleocapsid epitope KTFPPTEPK361-369. CD8+ T cell lines unable to recognize variant epitopes have diverse T cell receptor repertoires. These data demonstrate the potential for T cell evasion and highlight the need for ongoing surveillance for variants capable of escaping T cell as well as humoral immunity.This work is supported by the UK Medical Research Council (MRC); Chinese Academy of Medical Sciences(CAMS) Innovation Fund for Medical Sciences (CIFMS), China; National Institute for Health Research (NIHR)Oxford Biomedical Research Centre, and UK Researchand Innovation (UKRI)/NIHR through the UK Coro-navirus Immunology Consortium (UK-CIC). Sequencing of SARS-CoV-2 samples and collation of data wasundertaken by the COG-UK CONSORTIUM. COG-UK is supported by funding from the Medical ResearchCouncil (MRC) part of UK Research & Innovation (UKRI),the National Institute of Health Research (NIHR),and Genome Research Limited, operating as the Wellcome Sanger Institute. T.I.d.S. is supported by a Well-come Trust Intermediate Clinical Fellowship (110058/Z/15/Z). L.T. is supported by the Wellcome Trust(grant number 205228/Z/16/Z) and by theUniversity of Liverpool Centre for Excellence in Infectious DiseaseResearch (CEIDR). S.D. is funded by an NIHR GlobalResearch Professorship (NIHR300791). L.T. and S.C.M.are also supported by the U.S. Food and Drug Administration Medical Countermeasures Initiative contract75F40120C00085 and the National Institute for Health Research Health Protection Research Unit (HPRU) inEmerging and Zoonotic Infections (NIHR200907) at University of Liverpool inpartnership with Public HealthEngland (PHE), in collaboration with Liverpool School of Tropical Medicine and the University of Oxford.L.T. is based at the University of Liverpool. M.D.P. is funded by the NIHR Sheffield Biomedical ResearchCentre (BRC – IS-BRC-1215-20017). ISARIC4C is supported by the MRC (grant no MC_PC_19059). J.C.K.is a Wellcome Investigator (WT204969/Z/16/Z) and supported by NIHR Oxford Biomedical Research Centreand CIFMS. The views expressed are those of the authors and not necessarily those of the NIHR or MRC
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Current Orthopaedic Residency Letters of Recommendation Are Not Biased by Gender of Applicant.
Letters of recommendation (LORs) are highly influential in the residency selection process. Differences in language and length of LORs by gender have been demonstrated for applicants applying to surgical residencies and fellowships. This had yet to be studied in orthopaedic surgery. Given the gender disparity in the field, we sought to investigate the impact of gender on orthopaedic residency applicant LORs. We hypothesized that differences in length and language would be present for women applicants as compared to men. LORs for 2019 to 2020 applicants who applied to a single academic institution were selected for review. Female and male applicants were matched by medical school attended and United States Medical Licensing Examination Step 1 score. LORs were analyzed using both qualitative and quantitative analyses. Letters were evaluated for their word count, presence of language terms, and frequency of language terms. A similar subgroup language analysis was performed for standardized LORs (SLORs). Six hundred fifty-six applicants met the initial screening criteria-126 women and 530 men. After matching, 71 female applicants were paired with 111 male applicants. Word count was, on average, longer for female applicants. LORs for female applicants were more likely to contain language terms that characterized their ability, achievement, participation in athletics, awards received, fit, leadership, and personality traits. Of these terms, ability and participation in athletics were also found more frequently in LORs written for women. In addition, language characterizing technical skills was found more frequently in LORs of female applicants. Similar codes were found to be statistically significant in the SLOR subgroup analysis. This study highlights that current orthopaedic surgery residency LORs do not appear to be biased by applicant gender. LORs were longer for female applicants and described them more positively. Future female orthopaedic residency applicants should be assured that current female candidates are applying with at least similar if not greater subjective qualifications to their male counterparts based on the findings of this study
Factors Associated with Long-Term Survival of Family Businesses: Duration Analysis
Family business, Family firm, Business owning family, Disaster resiliency, Family business sustainability, Family business survival, Duration analysis,
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Global Surgery 2030: a roadmap for high income country actors.
The Millennium Development Goals have ended and the Sustainable Development Goals have begun, marking a shift in the global health landscape. The frame of reference has changed from a focus on 8 development priorities to an expansive set of 17 interrelated goals intended to improve the well-being of all people. In this time of change, several groups, including the Lancet Commission on Global Surgery, have brought a critical problem to the fore: 5 billion people lack access to safe, affordable surgical and anaesthesia care when needed. The magnitude of this problem and the world's new focus on strengthening health systems mandate reimagined roles for and renewed commitments from high income country actors in global surgery. To discuss the way forward, on 6 May 2015, the Commission held its North American launch event in Boston, Massachusetts. Panels of experts outlined the current state of knowledge and agreed on the roles of surgical colleges and academic medical centres; trainees and training programmes; academia; global health funders; the biomedical devices industry, and news media and advocacy organisations in building sustainable, resilient surgical systems. This paper summarises these discussions and serves as a consensus statement providing practical advice to these groups. It traces a common policy agenda between major actors and provides a roadmap for maximising benefit to surgical patients worldwide. To close the access gap by 2030, individuals and organisations must work collectively, interprofessionally and globally. High income country actors must abandon colonial narratives and work alongside low and middle income country partners to build the surgical systems of the future