Du droit comme facteur déterminant de la participation sociale des personnes ayant des incapacités

Le présent article a pour objectifs de proposer à la communauté juridique les résultats des travaux du Comité québécois sur la Classification internationale des déficiences, incapacités et handicaps (CQCIDIH) depuis 1991 et de les appliquer concrètement au droit québécois. Ces travaux amènent en effet un nouvel éclairage au droit des personnes ayant des incapacités, en particulier en matière de discrimination fondée sur le « handicap ». Dans la première partie, l'approche conceptuelle élaborée dans ces travaux récents ainsi que la terminologie qui l'accompagne sont présentées. Dans la seconde partie, la vision du droit qui se dégage des travaux du CQCIDIH est d'abord analysée. On procède ensuite à la première application au droit québécois de la proposition du CQCIDIH. On examine concrètement en quoi le droit est un facteur environnemental déterminant de la participation sociale des personnes ayant des incapacités, potentiellement un facilitateur de leur participation sociale ou un obstacle à celle-ci.The purpose of this paper is to propose to the legal community the results of work performed by QCICIDH (the Québec Committee for the International Classification of Impairments, Disabilities and Handicaps) since 1991 and to apply them specifically to Québec law. This work sheds new light on people with disabilities, particularly regarding discrimination based on « handicap ». The first part presents the conceptual approach developed in this recent work and the terminology that accompanies it. In the second part, an analysis is made of the perspective on law that emerges from QCICIDH work and an initial application to Québec law of the QCICIDH proposal is described. An in-depth examination is then made of the law as a determining environmental factor in the social participation of persons with disabilities and how it may potentially be a facilitator or an obstacle to such social participation

Targeting dendritic cell dysfunction to circumvent anti-PD1 resistance in head and neck cancer

PURPOSE: Neoadjuvant anti-PD1 (aPD1) therapies are being explored in surgically resectable head and neck squamous cell carcinoma (HNSCC). Encouraging responses have been observed, but further insights into the mechanisms underlying resistance and approaches to improve responses are needed. EXPERIMENTAL DESIGN: We integrated data from syngeneic mouse oral carcinoma (MOC) models and neoadjuvant pembrolizumab HNSCC patient tumor RNA-sequencing data to explore the mechanism of aPD1 resistance. Tumors and tumor-draining lymph nodes (DLN) from MOC models were analyzed for antigen-specific priming. CCL5 expression was enforced in an aPD1-resistant model. RESULTS: An aPD1-resistant mouse model showed poor priming in the tumor DLN due to type 1 conventional dendritic cell (cDC1) dysfunction, which correlated with exhausted and poorly responsive antigen-specific T cells. Tumor microenvironment analysis also showed decreased cDC1 in aPD1-resistant tumors compared with sensitive tumors. Following neoadjuvant aPD1 therapy, pathologic responses in patients also positively correlated with baseline transcriptomic cDC1 signatures. In an aPD1-resistant model, intratumoral cDC1 vaccine was sufficient to restore aPD1 response by enhancing T-cell infiltration and increasing antigen-specific responses with improved tumor control. Mechanistically, CCL5 expression significantly correlated with neoadjuvant aPD1 response and enforced expression of CCL5 in an aPD1-resistant model, enhanced cDC1 tumor infiltration, restored antigen-specific responses, and recovered sensitivity to aPD1 treatment. CONCLUSIONS: These data highlight the contribution of tumor-infiltrating cDC1 in HNSCC aPD1 response and approaches to enhance cDC1 infiltration and function that may circumvent aPD1 resistance in patients with HNSCC

Complete Genome Sequence of \u3ci\u3eBurkholderia phymatum\u3c/i\u3e STM815T , a Broad Host Range and Efficient Nitrogen-Fixing Symbiont of \u3ci\u3eMimosa\u3c/i\u3e Species

Burkholderia phymatum is a soil bacterium able to develop a nitrogen-fixing symbiosis with species of the legume genus Mimosa, and is frequently found associated specifically with Mimosa pudica. The type strain of the species, STM 815T , was isolated from a root nodule in French Guiana in 2000. The strain is an aerobic, motile, non-spore forming, Gram-negative rod, and is a highly competitive strain for nodulation compared to other Mimosa symbionts, as it also nodulates a broad range of other legume genera and species. The 8,676,562 bp genome is composed of two chromosomes (3,479,187 and 2,697,374 bp), a megaplasmid (1,904,893 bp) and a plasmid hosting the symbiotic functions (595,108 bp)

A cognitive prosthesis for complex decision-making

While simple heuristics can be ecologically rational and effective in naturalistic decision making contexts, complex situations require analytical decision making strategies, hypothesis-testing and learning. Sub-optimal decision strategies – using simplified as opposed to analytic decision rules – have been reported in domains such as healthcare, military operational planning, and government policy making. We investigate the potential of a computational toolkit called “IMAGE” to improve decision-making by developing structural knowledge and increasing understanding of complex situations. IMAGE is tested within the context of a complex military convoy management task through (a) interactive simulations, and (b) visualization and knowledge representation capabilities. We assess the usefulness of two versions of IMAGE (desktop and immersive) compared to a baseline. Results suggest that the prosthesis helped analysts in making better decisions, but failed to increase their structural knowledge about the situation once the cognitive prosthesis is removed

Parallel genome-scale loss of function screens in 216 cancer cell lines for the identification of context-specific genetic dependencies

Using a genome-scale, lentivirally delivered shRNA library, we performed massively parallel pooled shRNA screens in 216 cancer cell lines to identify genes that are required for cell proliferation and/or viability. Cell line dependencies on 11,000 genes were interrogated by 5 shRNAs per gene. The proliferation effect of each shRNA in each cell line was assessed by transducing a population of 11M cells with one shRNA-virus per cell and determining the relative enrichment or depletion of each of the 54,000 shRNAs after 16 population doublings using Next Generation Sequencing. All the cell lines were screened using standardized conditions to best assess differential genetic dependencies across cell lines. When combined with genomic characterization of these cell lines, this dataset facilitates the linkage of genetic dependencies with specific cellular contexts (e.g., gene mutations or cell lineage). To enable such comparisons, we developed and provided a bioinformatics tool to identify linear and nonlinear correlations between these features

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Stress analysis and fabrication of composite monocoque bicycle frames

An analytical and experimental investigation was conducted to study the design and fabrication of carbon fiber track bicycle frames. A finite element software was used for the geometry development, laminate configuration, and for predicting failure using the maximum stress criteria. A load case and boundary conditions simulating actual riding conditions were developed. The stresses in each of the composite layers were found to be lower than the allowable stresses because of a properly designed geometry and laminate. Two composite frames were fabricated using the hand lay-up technique, using unidirectional and woven carbon fiber pre-preg material over an internal foam core. Using static testing techniques and comparisons with traditional tubular frames, the carbon fiber prototypes were shown to be better in all rigidity aspects. Combining the experimental and theoretical results, a good understanding of the critical problems related to composite monocoque bicycle frame design was obtained