Centering the Complexity of Long-Term Unemployment: Lessons Learned from a Critical Occupational Science Inquiry

Inquiries that rely on temporal framings to demarcate long-term unemployment risk generating partial understandings and grounding unrealistic policy solutions. In contrast, this four-phase two-context study aimed to generate complex understandings of post-recession long-term unemployment in North America. Grounded in a critical occupational perspective, this collaborative ethnographic study also drew on street-level bureaucracy and governmentality perspectives to understand how social policies and discursive constructions shaped people’s everyday ‘doing’ within the arena of long-term unemployment. Across three phases, study methods included interviews with 15 organizational stakeholders who oversaw employment support services; interviews, participant observations, and focus groups with 18 people who provided front-line employment support services; and interviews, participant observations, time diaries, and occupational mapping with 23 people who self-identified as being long-term unemployed. We draw on selected interviews and mapping data to illustrate how participants’ definitions and experiences of long-term unemployment reflected and moved beyond dominant temporally based framings. These findings reinforce the need to expand the dominant conceptualizations of long-term unemployment that shape scholarly inquiries and policy responses. Reflections on the benefits and challenges of this study’s design also reinforce the need to use multiple, flexible methods to center the complexity of long-term unemployment as it is experienced in everyday life.Medicine, Faculty ofNon UBCOccupational Science and Occupational Therapy, Department ofReviewedFacult

Potentiels et verrous d'une filière protéagineuse pour une agriculture durable en Bourgogne

International audienc

The NADPH Oxidase NOX4 Drives Cardiac Differentiation: Role in Regulating Cardiac Transcription Factors and MAP Kinase Activation

Reactive oxygen species (ROS) generated by the NOX family of NADPH oxidases have been described to act as second messengers regulating cell growth and differentiation. However, such a function has hitherto not been convincingly demonstrated. We investigated the role of NOX-derived ROS in cardiac differentiation using mouse embryonic stem cells. ROS scavengers prevented the appearance of spontaneously beating cardiac cells within embryoid bodies. Down-regulation of NOX4, the major NOX isoform present during early stages of differentiation, suppressed cardiogenesis. This was rescued by a pulse of low concentrations of hydrogen peroxide 4 d before spontaneous beating appears. Mechanisms of ROS-dependent signaling included p38 mitogen-activated protein kinase (MAPK) activation and nuclear translocation of the cardiac transcription factor myocyte enhancer factor 2C (MEF2C). Our results provide first molecular evidence that the NOX family of NADPH oxidases regulate vertebrate developmental processes

Rare predicted loss-of-function variants of type I IFN immunity genes are associated with life-threatening COVID-19

BackgroundWe previously reported that impaired type I IFN activity, due to inborn errors of TLR3- and TLR7-dependent type I interferon (IFN) immunity or to autoantibodies against type I IFN, account for 15-20% of cases of life-threatening COVID-19 in unvaccinated patients. Therefore, the determinants of life-threatening COVID-19 remain to be identified in similar to 80% of cases.MethodsWe report here a genome-wide rare variant burden association analysis in 3269 unvaccinated patients with life-threatening COVID-19, and 1373 unvaccinated SARS-CoV-2-infected individuals without pneumonia. Among the 928 patients tested for autoantibodies against type I IFN, a quarter (234) were positive and were excluded.ResultsNo gene reached genome-wide significance. Under a recessive model, the most significant gene with at-risk variants was TLR7, with an OR of 27.68 (95%CI 1.5-528.7, P=1.1x10(-4)) for biochemically loss-of-function (bLOF) variants. We replicated the enrichment in rare predicted LOF (pLOF) variants at 13 influenza susceptibility loci involved in TLR3-dependent type I IFN immunity (OR=3.70[95%CI 1.3-8.2], P=2.1x10(-4)). This enrichment was further strengthened by (1) adding the recently reported TYK2 and TLR7 COVID-19 loci, particularly under a recessive model (OR=19.65[95%CI 2.1-2635.4], P=3.4x10(-3)), and (2) considering as pLOF branchpoint variants with potentially strong impacts on splicing among the 15 loci (OR=4.40[9%CI 2.3-8.4], P=7.7x10(-8)). Finally, the patients with pLOF/bLOF variants at these 15 loci were significantly younger (mean age [SD]=43.3 [20.3] years) than the other patients (56.0 [17.3] years; P=1.68x10(-5)).ConclusionsRare variants of TLR3- and TLR7-dependent type I IFN immunity genes can underlie life-threatening COVID-19, particularly with recessive inheritance, in patients under 60 years old