30 research outputs found
Communication brève sur les perceptions et les comportements postulants potentiels aux études de médecine par rapport à la recherche en lien avec l’admission dans une faculté de médecine canadienne
Background: Aspiring medical students behave based on their perception of what is valued in the selection process. While research experience is not explicitly considered in most Canadian admissions policies, it is commonly held as valuable within aspiring medical student communities. The purpose of this study is to describe the perceptions and behaviours of aspiring medical students with respect to gaining research experience in support of their medical school applications.
Methods: We surveyed prospective applicants of Canadian medical schools between August 2021 and November 2021, then compiled descriptive statistics pertaining to their perceptions and behaviours.
Results: Respondents affirmed the belief that research experience is valued in medical school admissions processes. They reported spending approximately 13 hours per week engaged in research, which usually did not yield publication or presentation recognition.
Conclusion: Aspiring medical students invest substantial time and energy in research experiences to benefit their applications. There is room for medical schools to be more transparent about the value of research experience in their admissions processes.Contexte : Le comportement des candidats aux études de médecine est déterminé par leur perception de ce qui est valorisé dans le processus de sélection. Tandis que la plupart des établissements canadiens ne mentionnent pas explicitement l’expérience en recherche comme prérequis d’admission, les futurs candidats, eux, voient une telle expérience comme un atout précieux. L’objectif de cette étude est de décrire les perceptions et les comportements des futurs étudiants en médecine par rapport à l’acquisition d’une expérience en recherche en appui à leur demande d’admission dans une école de médecine.
Méthodes : Nous avons interrogé des postulants potentiels aux programmes de médecine au Canada entre août 2021 et novembre 2021, et nous avons compilé des statistiques descriptives relatives à leurs perceptions et à leurs comportements.
Résultats : Les répondants ont affirmé croire que l’expérience en recherche est valorisée dans les processus d’admission aux facultés de médecine. Ils ont déclaré consacrer environ 13 heures par semaine à la recherche, qui, le plus souvent, n’a pas mené à des publications ou des présentations.
Conclusion : Les futurs candidats aux études de médecine investissent beaucoup de temps et d’énergie dans des activités de recherche afin d’améliorer leur dossier de candidature. Les facultés de médecine devraient se prononcer de manière transparente sur l’importance attribuée à l’expérience en recherche dans le cadre de leur processus d’admission
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Pooling Different Placebos as a Control Group in a Randomized Platform Trial: Benefits and Challenges From Experience in the ACTIV-2 COVID-19 Trial
Adaptive platform trials were implemented during the coronavirus disease 2019 (COVID-19) pandemic to rapidly evaluate therapeutics, including the placebo-controlled phase 2/3 ACTIV-2 trial, which studied 7 investigational agents with diverse routes of administration. For each agent, safety and efficacy outcomes were compared to a pooled placebo control group, which included participants who received a placebo for that agent or for other agents in concurrent evaluation. A 2-step randomization framework was implemented to facilitate this. Over the study duration, the pooled placebo design achieved a reduction in sample size of 6% versus a trial involving distinct placebo control groups for evaluating each agent. However, a 26% reduction was achieved during the period when multiple agents were in parallel phase 2 evaluation. We discuss some of the complexities implementing the pooled placebo design versus a design involving nonoverlapping control groups, with the aim of informing the design of future platform trials. Clinical Trials Registration. NCT04518410
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Statistical Challenges When Analyzing SARS-CoV-2 RNA Measurements Below the Assay Limit of Quantification in COVID-19 Clinical Trials
Most clinical trials evaluating coronavirus disease 2019 (COVID-19) therapeutics include assessments of antiviral activity. In recently completed outpatient trials, changes in nasal severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA levels from baseline were commonly assessed using analysis of covariance (ANCOVA) or mixed models for repeated measures (MMRM) with single imputation for results below assay lower limits of quantification (LLoQ). Analyzing changes in viral RNA levels with singly imputed values can lead to biased estimates of treatment effects. In this article, using an illustrative example from the ACTIV-2 trial, we highlight potential pitfalls of imputation when using ANCOVA or MMRM methods, and illustrate how these methods can be used when considering value
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Variant-Specific Viral Kinetics in Acute COVID-19
Understanding variant-specific differences in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral kinetics may explain differences in transmission efficiency and provide insights on pathogenesis and prevention. We evaluated SARS-CoV-2 kinetics from nasal swabs across multiple variants (Alpha, Delta, Epsilon, Gamma) in placebo recipients of the ACTIV-2/A5401 trial. Delta variant infection led to the highest maximum viral load and shortest time from symptom onset to viral load peak. There were no significant differences in time to viral clearance across the variants. Viral decline was biphasic with first- and second-phase decays having half-lives of 11 hours and 2.5 days, respectively, with differences among variants, especially in the second phase. These results suggest that while variant-specific differences in viral kinetics exist, post-peak viral load all variants appeared to be efficiently cleared by the host. Clinical Trials Registration. NCT04518410
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Targeting PI3Kδ function for amelioration of murine chronic graft-versus-host disease
Chronic graft-versus-host disease (cGVHD) is a leading cause of morbidity and mortality following allotransplant. Activated donor effector T cells can differentiate into pathogenic T helper (Th)-17 cells and germinal center (GC)-promoting T follicular helper (Tfh) cells, resulting in cGVHD. Phosphoinositide-3-kinase-δ (PI3Kδ), a lipid kinase, is critical for activated T cell survival, proliferation, differentiation, and metabolism. We demonstrate PI3Kδ activity in donor T cells that become Tfh cells is required for cGVHD in a nonsclerodermatous multiorgan system disease model that includes bronchiolitis obliterans (BO), dependent upon GC B cells, Tfhs, and counterbalanced by T follicular regulatory cells, each requiring PI3Kδ signaling for function and survival. Although B cells rely on PI3Kδ pathway signaling and GC formation is disrupted resulting in a substantial decrease in Ig production, PI3Kδ kinase-dead mutant donor bone marrow-derived GC B cells still supported BO cGVHD generation. A PI3Kδ-specific inhibitor, compound GS-649443, that has superior potency to idelalisib while maintaining selectivity, reduced cGVHD in mice with active disease. In a Th1-dependent and Th17-associated scleroderma model, GS-649443 effectively treated mice with active cGVHD. These data provide a foundation for clinical trials of US Food and Drug Administration (FDA)-approved PI3Kδ inhibitors for cGVHD therapy in patients
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Immune Status and SARS-CoV-2 Viral Dynamics
Immunocompromised individuals are disproportionately affected by severe coronavirus disease 2019, but immune compromise is heterogenous, and viral dynamics may vary by the degree of immunosuppression. In this study, we categorized ACTIV-2/A5401 participants based on the extent of immunocompromise into none, mild, moderate, and severe immunocompromise. Moderate/severe immunocompromise was associated with higher nasal viral load at enrollment (adjusted difference in means: 0.47 95% confidence interval, .12-.83 log10 copies/mL) and showed a trend toward higher cumulative nasal RNA levels and plasma viremia compared to nonimmunocompromised individuals. Immunosuppression leads to greater viral shedding and altered severe acute respiratory syndrome coronavirus 2 viral decay kinetics. Clinical Trials Registration. NCT04518410
Mechanisms of Response and Resistance to Combined Decitabine and Ipilimumab for Advanced Myeloid Disease
The challenge of eradicating leukemia in patients with acute myelogenous leukemia (AML) after initial cytoreduction has motivated modern efforts to combine synergistic active modalities including immunotherapy. Recently, the ETCTN/CTEP 10026 study tested the combination of the DNA methyltransferase inhibitor decitabine together with the immune checkpoint inhibitor ipilimumab for AML/myelodysplastic syndrome (MDS) either after allogeneic hematopoietic stem cell transplantation (HSCT) or in the HSCT-naïve setting. Integrative transcriptome-based analysis of 304 961 individual marrow-infiltrating cells for 18 of 48 subjects treated on study revealed the strong association of response with a high baseline ratio of T to AML cells. Clinical responses were predominantly driven by decitabine-induced cytoreduction. Evidence of immune activation was only apparent after ipilimumab exposure, which altered CD4+ T-cell gene expression, in line with ongoing T-cell differentiation and increased frequency of marrow-infiltrating regulatory T cells. For post-HSCT samples, relapse could be attributed to insufficient clearing of malignant clones in progenitor cell populations. In contrast to AML/MDS bone marrow, the transcriptomes of leukemia cutis samples from patients with durable remission after ipilimumab monotherapy showed evidence of increased infiltration with antigen-experienced resident memory T cells and higher expression of CTLA-4 and FOXP3. Altogether, activity of combined decitabine and ipilimumab is impacted by cellular expression states within the microenvironmental niche of leukemic cells. The inadequate elimination of leukemic progenitors mandates urgent development of novel approaches for targeting these cell populations to generate long-lasting responses. This trial was registered at www.clinicaltrials.gov as #NCT02890329
Advances in multiangle satellite remote sensing of speciated airborne particulate matter and association with adverse health effects: from MISR to MAIA
Inhalation of airborne particulate matter (PM) is associated with a variety of adverse health outcomes. However, the relative toxicity of specific PM types—mixtures of particles of varying sizes, shapes, and chemical compositions—is not well understood. A major impediment has been the sparse distribution of surface sensors, especially those measuring speciated PM. Aerosol remote sensing from Earth orbit offers the opportunity to improve our understanding of the health risks associated with different particle types and sources. The Multi-angle Imaging SpectroRadiometer (MISR) instrument aboard NASA’s Terra satellite has demonstrated the value of near-simultaneous observations of backscattered sunlight from multiple view angles for remote sensing of aerosol abundances and particle properties over land. The Multi-Angle Imager for Aerosols (MAIA) instrument, currently in development, improves on MISR’s sensitivity to airborne particle composition by incorporating polarimetry and expanded spectral range. Spatiotemporal regression relationships generated using collocated surface monitor and chemical transport model data will be used to convert fractional aerosol optical depths retrieved from MAIA observations to near-surface PM_(10), PM_(2.5), and speciated PM_(2.5). Health scientists on the MAIA team will use the resulting exposure estimates over globally distributed target areas to investigate the association of particle species with population health effects
Transcending the Male–Female Binary in Biomedical Research: Constellations, Heterogeneity, and Mechanism When Considering Sex and Gender
Accounting for the influences of sex- and gender-related factors on health is one of the most interesting and important challenges in contemporary health research. In biomedical research, models, experimental designs, and statistical analyses create particular challenges in attempting to incorporate the complex, dynamic, and context-dependent constructs of sex and gender. Here, we offer conceptual elaborations of the constructs of sex and gender and discuss their application in biomedical research, including a more mechanism-oriented and context-driven approach to experimental design integrating sex and gender. We highlight how practices of data visualization, statistical analysis, and rhetoric can be valuable tools in expanding the operationalization of sex and gender biomedical science and reducing reliance on a male–female binary approach