Évaluation d’un programme de recherche canadien pour les résidents en anesthésiologie par rapport aux normes nationales à l’aide d’un modèle logique : une étude d’amélioration de la qualité

Background: Canadian specialty training programs are expected to deliver curriculum content and assess competencies related to the CanMEDS Scholar role. We evaluated our residency research program and benchmarked it against national norms for quality improvement purposes. Methods: In 2021, we reviewed departmental curriculum documents and surveyed current and recently graduated residents.  We applied a logic model framework to assess if our program’s inputs, activities, and outputs addressed the relevant CanMeds Scholar competencies.  We then descriptively benchmarked our results against a 2021 environmental scan of Canadian anesthesiology resident research programs. Results: Local program content was successfully mapped to competencies.  The local survey response rate was 40/55 (73%).  In benchmarking, our program excelled in providing milestone-related assessments, research funding, administrative, supervisory, and methodologic support, and requiring a literature review, proposal presentation, and local abstract submission as output.  Acceptable activities to meet research requirements vary greatly among programs.  Balancing competing clinical and research responsibilities was a frequently reported challenge.   Conclusions: The logic model framework was easily applied and demonstrated our program benchmarked well against national norms.  National level dialogue is needed to develop specific, consistent scholar role activities and competency assessments to bridge the gap between expected outcome standards and education practice.Contexte : Les programmes de spécialité canadiens doivent proposer un contenu de formation en lien avec le rôle CanMEDS d’érudit et évaluer les compétences qui s’y attachent. Nous avons évalué notre programme de résidence en recherche par rapport aux normes nationales en la matière à des fins d’amélioration de la qualité. Méthodes : En 2021, nous avons examiné les documents du programme d’études du département et interrogé des résidents et des médecins récemment diplômés. Nous avons utilisé un modèle logique pour déterminer si les intrants, les activités et les extrants de notre programme couvraient adéquatement les compétences pertinentes liées au rôle CanMeds d’érudit. Nous avons ensuite comparé de façon descriptive nos résultats à une analyse du milieu des programmes de résidence canadiens en recherche en anesthésiologie effectuée la même année. Résultats : Nous avons établi une correspondance entre le contenu du programme local et les compétences. Le taux de réponse à l’enquête était de 40/55 (73 %). D’après l’analyse comparative, notre programme se démarque par l’offre d’évaluations d’étape, de fonds de recherche, de soutien administratif, de supervision, d’orientation méthodologique, et, en ce qui concerne les extrants, par l’exigence d’une analyse documentaire, de la présentation d’une proposition et de la soumission d’un résumé à l’université. Les activités admissibles pour répondre aux exigences de la recherche varient considérablement d’un programme à l’autre. De nombreux répondants ont signalé la difficulté de concilier les responsabilités cliniques et de recherche. Conclusions : L’application du modèle logique a été aisée et elle a permis de montrer que notre programme respecte les normes nationales. Un dialogue au niveau national est nécessaire pour définir de manière précise et cohérente les activités et les évaluations des compétences en lien avec le rôle d’érudit afin de combler le fossé entre les normes quant aux résultats attendus et les pratiques des programmes

Centromere Protein B Null Mice are Mitotically and Meiotically Normal but Have Lower Body and Testis Weights

CENP-B is a constitutive centromere DNA-binding protein that is conserved in a number of mammalian species and in yeast. Despite this conservation, earlier cytological and indirect experimental studies have provided conflicting evidence concerning the role of this protein in mitosis. The requirement of this protein in meiosis has also not previously been described. To resolve these uncertainties, we used targeted disruption of the Cenpb gene in mouse to study the functional significance of this protein in mitosis and meiosis. Male and female Cenpb null mice have normal body weights at birth and at weaning, but these subsequently lag behind those of the heterozygous and wild-type animals. The weight and sperm content of the testes of Cenpb null mice are also significantly decreased. Otherwise, the animals appear developmentally and reproductively normal. Cytogenetic fluorescence-activated cell sorting and histological analyses of somatic and germline tissues revealed no abnormality. These results indicate that Cenpb is not essential for mitosis or meiosis, although the observed weight reduction raises the possibility that Cenpb deficiency may subtly affect some aspects of centromere assembly and function, and result in reduced rate of cell cycle progression, efficiency of microtubule capture, and/or chromosome movement. A model for a functional redundancy of this protein is presented

Analysis of pairwise comparison matrices: an empirical research

Pairwise comparison (PC) matrices are used in multi-attribute decision problems (MADM) in order to express the preferences of the decision maker. Our research focused on testing various characteristics of PC matrices. In a controlled experiment with university students (N = 227) we have obtained 454 PC matrices. The cases have been divided into 18 subgroups according to the key factors to be analyzed. Our team conducted experiments with matrices of different size given from different types of MADM problems. Additionally, the matrix elements have been obtained by different questioning procedures differing in the order of the questions. Results are organized to answer five research questions. Three of them are directly connected to the inconsistency of a PC matrix. Various types of inconsistency indices have been applied. We have found that the type of the problem and the size of the matrix had impact on the inconsistency of the PC matrix. However, we have not found any impact of the questioning order. Incomplete PC matrices played an important role in our research. The decision makers behavioral consistency was as well analyzed in case of incomplete matrices using indicators measuring the deviation from the final order of alternatives and from the final score vector

Denial of long-term issues with agriculture on tropical peatlands will have devastating consequences

Non peer reviewe

Screening ethnically diverse human embryonic stem cells identifies a chromosome 20 minimal amplicon conferring growth advantage

The International Stem Cell Initiative analyzed 125 human embryonic stem (ES) cell lines and 11 induced pluripotent stem (iPS) cell lines, from 38 laboratories worldwide, for genetic changes occurring during culture. Most lines were analyzed at an early and late passage. Single-nucleotide polymorphism (SNP) analysis revealed that they included representatives of most major ethnic groups. Most lines remained karyotypically normal, but there was a progressive tendency to acquire changes on prolonged culture, commonly affecting chromosomes 1, 12, 17 and 20. DNA methylation patterns changed haphazardly with no link to time in culture. Structural variants, determined from the SNP arrays, also appeared sporadically. No common variants related to culture were observed on chromosomes 1, 12 and 17, but a minimal amplicon in chromosome 20q11.21, including three genes expressed in human ES cells, ID1, BCL2L1 and HM13, occurred in >20% of the lines. Of these genes, BCL2L1 is a strong candidate for driving culture adaptation of ES cells

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

Correction to: Cluster identification, selection, and description in Cluster randomized crossover trials: the PREP-IT trials

An amendment to this paper has been published and can be accessed via the original article

Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts

Visualising antigen-specific T-cells during primary and persistent infection with Epstein-Barr virus

Cytotoxic T lymphocytes play an important role in mediating host immune reactions to viruses and other pathogens. Selective mechanisms operate during V(D)J recombination to enhance the diversity of the T cell repertoire that is generated, particularly in the CDR3 regions of the TCR, which mediate peptide recognition. The influence of V gene 3' sequences on the composition of the CDR3 loop in TCR β chains is analysed; in particular, A/T-rich coding termini are shown to be more susceptible to exonuclease "nibbling" during recombination. The recent development of peptide-MHC tetrameric complexes has enabled us to detect T lymphocytes according to their antigen specificity. Their use in detection and characterisation of EBV-specific CD8+ T cells during the primary acute phase of infection is described here. In particular, CTL responses to EBV lytic cycle antigens have only recently been reported and this study reveals unexpectedly high frequencies of activated, circulating CD8+ T lymphocytes which are directed towards lytic cycle epitopes, compared to well-characterised latent cycle antigens. In a second cohort of healthy long term asymptomatic donors, the frequency of CD8+ T cells recognising EBV lytic and latent cycle antigens was analysed by tetramer staining, ELISpot assays and limiting dilution assays; the tetramers detected antigen-specific CD8+ T lymphocytes with greater efficiency than other methods. Lytic cycle antigen-specific T lymphocytes were clearly detectable in all the asymptomatic donors, at higher frequencies than those specific for latent antigens. The final section of this thesis investigates the existence of enriched populations of EBV-specific T lymphocytes found within synovial joint fluid of rheumatoid arthritis patients. Although these cells do not appear to be directly involved in the initiation of disease, their ability to secrete proinflammatory cytokines within joints probably contributes to the maintenance of chronic inflammation in these patients.</p