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Imaginaires francophones de l’intelligence artificielle (IA)
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Prothrombotic Biomarkers Are Not Altered by Wood Smoke: A Pilot Controlled Exposure Study
Get PDFInhalation of wood smoke (WS) has been associated with increased risk of cardiovascular events, including heart attacks and strokes, both of which are caused in part by the thrombotic occlusion of blood vessels. To characterize the effects of WS on levels of established, circulating prothrombotic biomarkers, healthy human subjects at rest were exposed to WS (500 μg/m3) or filtered air for 2 h. Plasma samples were then used to assess markers of endogenous procoagulant activity: cellular activation (tissue factor-positive extracellular vesicles, TF + EVs), thrombin-antithrombin complexes (TAT), fibrin formation/breakdown (D-dimer), and thrombin generation potential. No significant differences in TF + EVs, TATs, D-dimer, or thrombin generation parameters were detected between WS- or filtered air-exposed individuals. Although females had significantly higher TATs and D-dimers, and slightly but non-significantly shorter thrombin generation lag times than males, there were no significant differences between WS- or air-exposed males or females in any measurements. These data suggest that acute WS exposure does not increase prothrombotic biomarkers in plasma
Building Access to High Quality Education: Improving Academic Readiness Scores For Low-Income K-8 Students in Granville and Vance Counties
Get PDFAccess to high-quality education is linked to improved health and quality of life across generations. Students in high-yield academic environments are more likely to develop strong foundational skills and connections to school systems, contributing to protection against behaviors such as substance use, violence, truancy, and unsafe sexual activity. As such, it is paramount to strengthen educational systems in historically under-resourced communities. In 2023–2024, Granville and Vance counties in North Carolina both performed below state and national averages in graduation rate, college and career readiness, and performance in math, science, and reading. These indicators can reflect the overall health of an educational system, with special consideration to students in kindergarten through 8th grade. External consultants collaborated with the local community to conduct a multidisciplinary assessment, identifying gaps and intervention strategies. Recommendations include improving cross-sector data sharing, fostering stronger connections between stakeholders across the continuum, and advocating for more equitable education policies.Master of Public Healt
Modelling international spread of clade IIb mpox on the Asian continent
Get PDFObjective: To understand and simulate international spread of the disease mpox, considering variations in sexual activity levels and international travel among men who have sex with men. Methods: We developed a mathematical model that considers differing sexual networks and the volume of international travel among men who have sex with men, calibrated to disease incidence data in Japan. We then used our model to simulate the potential international spread of mpox across 42 countries and territories on the Asian continent, assuming Japan as the origin of spread. Findings: Our simulations identified countries and territories at a high risk of mpox introduction, many being low- and middle-income countries and territories in the Western Pacific and South-East Asia regions. We found that the simulated risk of importation gradually shifted over time from the Western Pacific to the South-East Asia region, and later to the Eastern Mediterranean and European regions. This simulated pattern broadly aligns with actual mpox spread patterns observed between 2023 and 2024. Conclusion: Our multicountry model for mpox outbreaks can help project the possible trajectory of mpox spread across countries and territories on the Asian continent. Our findings warrant global efforts to contain mpox outbreaks, particularly support for low- and middle-income countries and territories which are at higher risk of introduction, so that the risk of continued spread across the Asian continent and beyond is reduced
A mixed methods pilot study of an internal coaching program within an academic emergency department
Get PDFBackground Over 60% of emergency medicine physicians experience burnout. Professional coaching of physicians may reduce emotional exhaustion and burnout, while improving quality of life and resilience; however, few studies have specifically investigated coaching’s impact on job satisfaction and burnout of emergency physicians. This study assesses the effects of a novel coaching program, which utilized internal professional coaches, on burnout and job satisfaction among emergency physicians in an academic emergency department. Methods In January 2022, an internal coaching program commenced for upper-level residents, fellows, and new faculty physicians. Participants engaged in individual coaching sessions, and group coaching sessions (n = 4) were offered to the entire department on a variety of topics (e.g., Leadership, Bedside Teaching). Quantitative data were collected to measure baseline and follow-up burnout and job satisfaction scores via the 2-Question Summative Score of Maslach Burnout Inventory [MBI] and Global Job Satisfaction [GJS] scales, respectively. Qualitative data gathered through surveys were inductively coded, leading to the identification of experiential themes. Results Thirty-two participants enrolled in individual coaching. Eighty-nine individual coaching sessions were delivered, totaling 69.34 h. Participants received a median of 2 (range:1–6) sessions. Department-wide baseline and follow-up survey response rates were 33.7% and 32.7%, respectively. Among all respondents, burnout symptoms did not change significantly (MBI: t(55) = 2.00, p = 0.15), but job satisfaction declined significantly, with mean GJS scores decreasing from 3.73 (SD = 0.70, 95% CI: 3.49–3.98) to 3.15 (SD = 0.91, 95% CI: 2.82–3.47). When analyzed by coaching participation, no significant differences were found in MBI (t(12) = 2.18, p = 0.71) or GJS (t(10) = 2.23, p = 0.75) scores between participants and non-participants. Thematic analysis highlighted benefits and challenges of the internal coaching program. Identified themes reinforced coaching best practices (e.g., solutions-focused sessions), provided context for future efforts (e.g., maintaining diverse perspectives), and highlighted advantages and disadvantages of internal coaches (e.g., familiarity versus privacy). Conclusion Our pilot study did not demonstrate a reduction in burnout or an increase in job satisfaction. However, internal coaching offers valuable opportunities for academic emergency departments, including unique benefits and challenges. Future research should explore system-level impacts on burnout and job satisfaction during coaching program implementation as well as cost-effectiveness
Transient APC/C inactivation by mTOR boosts glycolysis during cell cycle entry
Get PDFMammalian cells entering the cell cycle favour glycolysis to rapidly generate ATP and produce the biosynthetic intermediates that are required for rapid biomass accumulation1. Simultaneously, the ubiquitin-ligase anaphase-promoting complex/cyclosome and its coactivator CDH1 (APC/CCDH1) remains active, allowing origin licensing and blocking premature DNA replication. Paradoxically, glycolysis is reduced by APC/CCDH1 through the degradation of key glycolytic enzymes2, raising the question of how cells coordinate these mutually exclusive events to ensure proper cell division. Here we show that cells resolve this paradox by transiently inactivating the APC/C during cell cycle entry, which allows a transient metabolic shift favouring glycolysis. After mitogen stimulation, rapid mTOR-mediated phosphorylation of the APC/C adapter protein CDH1 at the amino terminus causes it to partially dissociate from the APC/C. This partial inactivation of the APC/C leads to the accumulation of PFKFB3, a rate-limiting enzyme for glycolysis, promoting a metabolic shift towards glycolysis. Delayed accumulation of phosphatase activity later removes CDH1 phosphorylation, restoring full APC/C activity, and shifting cells back to favouring oxidative phosphorylation. Thus, cells coordinate the simultaneous demands of cell cycle progression and metabolism through an incoherent feedforward loop, which transiently inhibits APC/C activity to generate a pulse of glycolysis that is required for mammalian cell cycle entry
Exosomes released from senescent cells and circulatory exosomes isolated from human plasma reveal aging-associated proteomic and lipid signatures.
Get PDFSenescence emerged as significant mechanism of aging and age-related diseases, offering an attractive target for clinical interventions. Senescent cells release a senescence-associated secretory phenotype (SASP), including exosomes that may act as signal transducers between distal tissues, and propagate secondary senescence. However, the composition of exosomal SASP components remains underexplored. We identified ~1,300 exosome proteins released by senescent primary human lung fibroblasts induced by three different senescence inducers. In parallel, a small human plasma cohort from young (20-26 years) and old (65-74 years) individuals revealed 1,350 exosome proteins and 171 plasma exosome proteins were altered in old individuals. Of the age-regulated plasma exosome proteins, we observed 52 exosomal SASP factors that were also regulated in exosomes from the senescent fibroblasts, SERPINs, Prothrombin, Coagulation factor V, Plasminogen, and Reelin. We identified 247 exosome lipids. Following senescence induction phosphatidylcholines, phosphatidylethanolamines, and sphingomyelins increased significantly indicating cellular membrane changes. Significantly changed proteins were related to extracellular matrix remodeling and inflammation, both potentially detrimental pathways that can damage surrounding tissues and even induce secondary senescence. Our proof-of-principle study - even though initially from a rather small human cohort - suggested potential senescence biomarker candidates, enabling future surveillance of senescence burden in the aging population
Neighborhood environment and incident diabetes, a neighborhood environment-wide association study (‘NE-WAS’): Results from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL)
Get PDFThe prevalence of type 2 diabetes is increasing among the Hispanic/Latino population. Type 2 diabetes incidence rates vary between neighborhoods, but no single aspect of the neighborhood environment is known to cause type 2 diabetes. Using data from the Hispanic Community Health Study/Study of Latinos cohort of 16,415 Hispanic/Latino adults in four major US cities, we conducted a neighborhood environment-wide association study to identify neighborhood measures or clusters of measures associated with diabetes incidence. Two-hundred and four neighborhood measures were calculated at the census tract level or within a 1-km buffer of participants' residential addresses. Independent covariate-adjusted and survey-weighted Poisson regressions were run for each neighborhood measure and incident diabetes. Principal component analysis of neighborhood measures was conducted to reduce dimensionality. No coherent pattern of neighborhood measures or principal component scores were associated with diabetes incidence within the cohort, though established individual-level risk factors such as age and family history were strongly associated with diabetes incidence. Results from our analysis did not indicate specific neighborhood measures, clusters, or patterns. Individual, rather than neighborhood, factors distinguish incident diabetes cases from non-cases
Protocol for the Redefining Maternal Anemia in Pregnancy and Postpartum (ReMAPP) study: A multisite, international, population-based cohort study to establish global hemoglobin thresholds for maternal anemia
Get PDFBACKGROUND: Anemia affects one in three pregnant women worldwide, with the greatest burden in South Asia and sub-Saharan Africa. During pregnancy, anemia has been linked to an increased risk of adverse maternal and neonatal health outcomes. Despite widespread recognition that anemia can complicate pregnancy, critical gaps persist in our understanding of the specific causes of maternal anemia and the cutoffs used to diagnose anemia in each trimester and in the postpartum period. METHODS AND ANALYSIS: The Redefining Maternal Anemia in Pregnancy and Postpartum (ReMAPP) study is a multisite, prospective, cohort study nested within the Pregnancy Risk, Infant Surveillance, and Measurement Alliance (PRISMA) Maternal and Newborn Health study. Research sites are located in Kenya, Ghana, Zambia, India, and Pakistan. Participants are up to 12,000 pregnant women who provide serial venous blood samples for hemoglobin assessment at five time points: at <20 weeks, 20 weeks, 28 weeks, and 36 weeks gestation and at six weeks postpartum. We will use two analytical approaches to estimate hemoglobin thresholds for defining anemia: (1) clinical decision limits for cutoffs in each trimester and at six weeks postpartum based on associations of hemoglobin levels with adverse maternal, fetal, and neonatal health outcomes and (2) reference limits for gestational-week-specific cutoffs and at six weeks postpartum for mild, moderate, and severe anemia based on tail statistical percentiles of hemoglobin values in a reference (i.e., clinically healthy) subpopulation. We will also conduct biomarker-intensive testing among a sub-sample of participants in each trimester to explore underlying contributing factors of maternal anemia. ETHICS AND DISSEMINATION: The study received local and national ethical approvals from all participating institutions. Findings from multisite analyses will be published among open-access, peer-reviewed journals and disseminated with local, national, and international partners. STRENGTHS AND LIMITATIONS: Novel study design to allow multiple analytical approaches (clinical decision limits and reference limits) in the same population to establish hemoglobin thresholds.Use of gold standard methods and external quality assurance programs to ensure harmonized hemoglobin measurement across sites.Inclusion of biomarker-intensive study arm to examine the etiology of anemia among pregnant women.All data is contributed by populations historically underrepresented in research in low- and middle-income countries. TRIALS REGISTRATION: ClinicalTrials.gov (PRISMA-MNH 2022; NCT05904145)
Global Division of Responsibility Sharing: How Refugee Systems Operate Through the Economic Management of Mobility and Immobility
Get PDFIn 2023, there were approximately 32 million refugees globally. Nine out of the ten countries with the highest origins of refugees were in the Global South; conversely, only three of the ten countries hosting the highest numbers of refugees were in the Global North. In this study, we introduce the conceptual framework of a global division of responsibility sharing to describe how functions of Global North countries as permanent “resettlement” countries and Global South countries as perpetual countries of “asylum” and “transit” constitute unequal burdens with unequal protections for refugees. We illustrate—theoretically and empirically—how the structural positions of state actors in a global network introduce and reify a global division in refugee flows. Empirically, we test and develop this framework with network analysis of refugee flows to countries of asylum from 1990 to 2015 in addition to employing data on monetary donations to the United Nations High Commissioner for Refugees (UNHCR) from 2017 to 2021. We (1) provide evidence of the structure and role of intermediary countries in refugee flows and (2) examine how UNHCR monetary aid conditions intermediary countries’ role of routing and transit. We illustrate how network constraints and monetary donations affect and constitute a global division in the management of historic and contemporary international refugee flows and explore the consequences of this global division for refugees’ access to resources and social and human rights