CBME framework to promote transition to senior

Residency programs across Canada are transitioning to Competence by Design (CBD). Our innovative framework improves the traditional transition to independent senior overnight call process by adding workplace-based (WBA) assessments. Our process ensures that faculty and residents have a shared understanding of what competencies need to be demonstrated before residents can work independently as the in-house senior resident overnight. This protocol is worth exploring; initial perceptions suggest an increase in resident confidence while on call and improved faculty comfort when paired with these senior residents. We believe that this in turn will be reflected in enhanced patient care

Évaluateurs attitrés : description d'une intervention éducative inédite visant à faciliter l'observation directe en milieu clinique

Background: The Department of Pediatrics at Queen’s University undertook a pilot project in July 2017 to increase the frequency of direct observations (DO) its residents received without affecting the patient flow in a busy hospital-based pediatric ambulatory care clinic. Facilitating DO for authentic workplace-based assessments is essential for assessing resident’s core competencies. The purpose of this study was to pilot an innovative education intervention to address the challenge of implementing DO in the clinical setting. Methods: The project allowed for staff physicians to act as “dedicated assessors” (DA), a faculty member who was scheduled to conduct direct observations of trainees’ clinical skills, while not acting as the attending physician on duty. At the end of the project, focus group interviews were conducted with faculty and residents, and thematic analysis was completed. Results: Participants reported an increase in the overall quality of feedback received during the observations performed by a DA, with more specific feedback and a broader focus of assessment. There seemed to be little disruption to patient care. Some residents described the observations as anxiety-provoking. Conclusions: Overall, this project provides insight into an educational approach that medical residency programs can apply to increase the frequency of workplace-based DO and boost the quality of feedback residents receive while maintaining the flow of already busy ambulatory care clinics.Contexte: En juillet 2017, le département de pédiatrie de l’Université Queen’s a lancé un projet pilote visant à augmenter la fréquence des observations directes (OD) dont faisaient l’objet ses résidents sans affecter le flux de patients dans une clinique achalandée de soins pédiatriques ambulatoires. Il est essentiel de faciliter l’OD, permettant une évaluation authentique en milieu de travail, afin d’évaluer les compétences fondamentales des résidents. L’objectif de cette étude était de piloter une intervention éducative novatrice pour relever le défi de la mise en place de l’OD dans le cadre clinique. Méthodes: Le projet permettait aux médecins d’agir en tant qu’« évaluateurs attitrés » (ÉA) : c’est-à-dire un membre du corps professoral chargé de l’observation directe des compétences cliniques des apprenants alors qu’il n’était pas le médecin traitant de service. Une analyse thématique a été réalisée sur la base d’entrevues de groupe menées avec le corps professoral et les résidents à la fin du projet. Résultats: Les participants ont signalé une augmentation de la qualité générale de la rétroaction reçue au cours des observations effectuées par un ÉA, notamment des commentaires plus précis et une évaluation plus complète. Il semble y avoir eu peu de perturbations dans les soins aux patients. Certains résidents ont décrit les observations comme étant anxiogènes. Conclusions: Dans l’ensemble, ce projet donne un aperçu d’une approche éducative qui peut être appliquée dans le cadre des programmes de résidence en médecine dans le but d’augmenter la fréquence des OD en milieu de travail et d’améliorer la qualité de la rétroaction reçue par les résidents sans perturber le flux de patients dans les cliniques de soins ambulatoires déjà très achalandées

An Analysis of Ontario's pre-service teacher candidates' attitudes and approach towards teaching the Holocaust

Unexpectedly, 79% of the respondents expressed no discomfort in teaching lessons about the Holocaust, despite the complexity and sensitivity of the topic. Respondents indicated the necessity of Holocaust Education as a means to explore historical evidence, while developing students' empathy and morals. Most significantly, along with an anti-racist pedagogy that was evident in the findings, the respondents expressed a strong commitment to advance Holocaust Education in their classrooms beyond what is currently specified in Ontario Ministry of Education curriculum documents

Effect of non-linearity in predicting doppler waveforms through a novel model

BACKGROUND: In pregnancy, the uteroplacental vascular system develops de novo locally in utero and a systemic haemodynamic & bio-rheological alteration accompany it. Any abnormality in the non-linear vascular system is believed to trigger the onset of serious morbid conditions like pre-eclampsia and/or intrauterine growth restriction (IUGR). Exact Aetiopathogenesis is unknown. Advancement in the field of non-invasive doppler image analysis and simulation incorporating non-linearities may unfold the complexities associated with the inaccessible uteroplacental vessels. Earlier modeling approaches approximate it as a linear system. METHOD: We proposed a novel electrical model for the uteroplacental system that uses MOSFETs as non-linear elements in place of traditional linear transmission line (TL) model. The model to simulate doppler FVW's was designed by including the inputs from our non-linear mathematical model. While using the MOSFETs as voltage-controlled switches, a fair degree of controlled-non-linearity has been introduced in the model. Comparative analysis was done between the simulated data and the actual doppler FVW's waveforms. RESULTS & DISCUSSION: Normal pregnancy has been successfully modeled and the doppler output waveforms are simulated for different gestation time using the model. It is observed that the dicrotic notch disappears and the S/D ratio decreases as the pregnancy matures. Both these results are established clinical facts. Effects of blood density, viscosity and the arterial wall elasticity on the blood flow velocity profile were also studied. Spectral analysis on the output of the model (blood flow velocity) indicated that the Total Harmonic Distortion (THD) falls during the mid-gestation. CONCLUSION: Total harmonic distortion (THD) is found to be informative in determining the Feto-maternal health. Effects of the blood density, the viscosity and the elasticity changes on the blood FVW are simulated. Future works are expected to concentrate mainly on improving the load with respect to varying non-linear parameters in the model. Heart rate variability, which accounts for the vascular tone, should also be included. We also expect the model to initiate extensive clinical or experimental studies in the near future

The Evolution of Amastin Surface Glycoproteins in Trypanosomatid Parasites

Amastin is a transmembrane glycoprotein found on the cell surfaces of trypanosomatid parasites. Encoded by a large, diverse gene family, amastin was initially described from the intracellular, amastigote stage of Trypanosoma cruzi and Leishmania donovani. Genome sequences have subsequently shown that the amastin repertoire is much larger in Leishmania relative to Trypanosoma. However, it is not known when this expansion occurred, whether it is associated with the origins of Leishmania and vertebrate parasitism itself, or prior to this. To examine the timing of amastin diversification, as well as the evolutionary mechanisms regulating gene repertoire and sequence diversity, this study sequenced the genomic regions containing amastin loci from two related insect parasites (Leptomonas seymouri and Crithidia sp.) and estimated a phylogeny for these and other amastin sequences. The phylogeny shows that amastin includes four subfamilies with distinct genomic positions, secondary structures, and evolution, which were already differentiated in the ancestral trypanosomatid. Diversification in Leishmania was initiated from a single ancestral locus on chromosome 34, with rapid derivation of novel loci through transposition and accelerated sequence divergence. This is absent from related organisms showing that diversification occurred after the origin of Leishmania. These results describe a substantial elaboration of amastin repertoire directly associated with the origin of Leishmania, suggesting that some amastin genes evolved novel functions crucial to cell function in leishmanial parasites after the acquisition of a vertebrate host

Gene expression modulation is associated with gene amplification, supernumerary chromosomes and chromosome loss in antimony-resistant Leishmania infantum

Antimonials remain the first line drug against the protozoan parasite Leishmania but their efficacy is threatened by resistance. We carried out a RNA expression profiling analysis comparing an antimony-sensitive and -resistant (Sb2000.1) strain of Leishmania infantum using whole-genome 70-mer oligonucleotide microarrays. Several genes were differentially expressed between the two strains, several of which were found to be physically linked in the genome. MRPA, an ATP-binding cassette (ABC) gene known to be involved in antimony resistance, was overexpressed in the antimony-resistant mutant along with three other tandemly linked genes on chromosome 23. This four gene locus was flanked by 1.4 kb repeated sequences from which an extrachromosomal circular amplicon was generated in the resistant cells. Interestingly, gene expression modulation of entire chromosomes occurred in the antimony-resistant mutant. Southern blots analyses and comparative genomic hybridizations revealed that this was either due to the presence of supernumerary chromosomes or to the loss of one chromosome. Leishmania parasites with haploid chromosomes were viable. Changes in copy number for some of these chromosomes were confirmed in another antimony-resistant strain. Selection of a partial revertant line correlated antimomy resistance levels and the copy number of aneuploid chromosomes, suggesting a putative link between aneuploidy and drug resistance in Leishmania

Trypanosomatid RACK1 Orthologs Show Functional Differences Associated with Translation Despite Similar Roles in Leishmania Pathogenesis

RACK1 proteins belong to the eukaryote WD40-repeat protein family and function as spatial regulators of multiple cellular events, including signaling pathways, the cell cycle and translation. For this latter role, structural and genetic studies indicate that RACK1 associates with the ribosome through two conserved positively charged amino acids in its first WD40 domain. Unlike RACK1s, including Trypanosoma brucei RACK1 (TbRACK1), only one of these two positively-charged residues is conserved in the first WD40 domain of the Leishmania major RACK1 ortholog, LACK. We compared virulence-attenuated LACK single copy (LACK/-) L. major, with L. major expressing either two LACK copies (LACK/LACK), or one copy each of LACK and TbRACK1 (LACK/TbRACK1), to evaluate the function of these structurally distinct RACK1 orthologs with respect to translation, viability at host temperatures and pathogenesis. Our results indicate that although the ribosome-binding residues are not fully conserved in LACK, both LACK and TbRACK1 co-sedimented with monosomes and polysomes in LACK/LACK and LACK/TbRACK1 L. major, respectively. LACK/LACK and LACK/TbRACK1 strains differed in their sensitivity to translation inhibitors implying that minor sequence differences between the RACK1 proteins can alter their functional properties. While biochemically distinguishable, both LACK/LACK and LACK/TbRACK1 lines were more tolerant of elevated temperatures, resistant to translation inhibitors, and displayed robust pathogenesis in vivo, contrasting to LACK/- parasites

Deletion of transketolase triggers a stringent metabolic response in promastigotes and loss of virulence in amastigotes of Leishmania mexicana

Transketolase (TKT) is part of the non-oxidative branch of the pentose phosphate pathway (PPP). Here we describe the impact of removing this enzyme from the pathogenic protozoan Leishmania mexicana. Whereas the deletion had no obvious effect on cultured promastigote forms of the parasite, the Δtkt cells were not infective to mice. Δtkt promastigotes were more susceptible to oxidative stress and various leishmanicidal drugs than wild-type, and metabolomics analysis revealed profound changes to metabolism in these cells. In addition to changes consistent with those directly related to the role of TKT in the PPP, central carbon metabolism was substantially decreased, the cells consumed significantly less glucose, flux through glycolysis diminished, and production of the main end products of metabolism was decreased. Only minor changes in RNA abundance from genes encoding enzymes in central carbon metabolism, however, were detected although fructose-1,6-bisphosphate aldolase activity was decreased two-fold in the knock-out cell line. We also showed that the dual localisation of TKT between cytosol and glycosomes is determined by the C-terminus of the enzyme and by engineering different variants of the enzyme we could alter its sub-cellular localisation. However, no effect on the overall flux of glucose was noted irrespective of whether the enzyme was found uniquely in either compartment, or in both

Comparative Expression Profiling of Leishmania: Modulation in Gene Expression between Species and in Different Host Genetic Backgrounds

The single-celled parasite Leishmania, transmitted by sand flies in more than 88 tropical and sub-tropical countries globally, infects man and other mammals, causing a spectrum of diseases called the leishmaniases. Over 12 million people are currently infected worldwide with 2 million new cases reported each year. The type of leishmaniasis that develops in the mammalian host is dependent on the species of infecting parasite and the immune response to infection (that can be influenced by host genetic variation). Our research is focused on identifying parasite factors that contribute to pathogenicity in the host and understanding how these might differ between parasite species that give rise to the different clinical forms of leishmaniasis. Molecules of this type might lead to new therapeutic tools in the longer term. In this paper, we report a comparative analysis of gene expression profiles in three Leishmania species that give rise to different types of disease, focusing on the intracellular stages that reside in mammalian macrophages. Our results show that there are only a small number of differences between these parasite species, with host genetics playing only a minor role in influencing the parasites' response to their intracellular habitat. These small changes may be significant, however, in determining the clinical outcome of infection