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Running in Circles: A Return to an Old Idea about Asylum Reform in Nineteenth-Century France
(Proceedings of the Western Society for French History, 2014) Nelson, Elizabeth
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Bias in pain care: What patient variables do providers report as influencing their treatment decisions?
(2024-10) Rose-McCandlish, Margaret; Hirsh, Adam; Mosher, Catherine; Stewart, Jesse
Racialized and low socioeconomic status (SES) patients are often under-treated for chronic pain, despite reporting more pain on average. This disparity is likely due to multiple systemic factors, including healthcare provider bias. Providers often treat patients differently for chronic pain depending on the patient’s race and SES, but little is known about providers’ awareness of the extent to which patient demographic variables influence their pain treatment decisions. The present study examined the variables that providers report as influencing their pain treatment decisions, whether these variables group together to form distinct factors, and whether providers who demonstrate racial or socioeconomic bias in their treatment decisions report different patient variables or factors as influencing their treatment decisions compared to providers who did not demonstrate biases. Four hundred thirty-two United States-based physician residents and fellows (“providers”) made treatment decisions for 12 computer-simulated patients with chronic pain who varied by race (Black/White) and SES (high/low). Providers then rated the level to which 15 different variables influenced their treatment decision-making. Robust repeated measures ANOVAs indicated that providers rated patient sex/gender, age, and race as the least influential variables in their pain treatment decisions for the simulated patients. For the factor analysis, I sequentially omitted variables to achieve proper model fit and reliability and arrived at a three-factor solution; I labelled these factors Demographic, Biomedical, and Psychosocial, according to the variables’ conceptual overlap. Robust repeated measures ANOVAs found that reported use of variables did not differ between the providers who demonstrated bias and those who did not demonstrate bias, nor did factor scores for the three factors. The present study suggests that providers have low awareness of the extent to which patient race and SES may influence their clinical decision-making in pain care. Results can help inform future research to improve interventions to reduce the impact of racial and socioeconomic bias on providers’ treatment decisions for patients with chronic pain.
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Immunological and Social Determinants of Asthma: From Cytokine Signaling to Air Pollution Disparities
(2024-10) Cheung, Cherry Cheuk Lam; Kaplan, Mark H.; Cook, Nathan; Cook-Mills, Joan; Yang, Kai
Asthma is a chronic respiratory disease characterized by airway inflammation and hyperresponsiveness, impacting 262 million individuals globally. This heterogeneous condition results from a complex interplay of genetic, environmental, and social factors. The pathophysiology involves dysregulated immune responses, particularly through cytokine signaling, and is exacerbated by environmental pollutants and social determinants of health (SDOH). This thesis aims to (1) elucidate novel cytokine signaling pathways involved in asthma, specifically a potential type II IL-9 receptor complex, and (2) evaluate the impact of California's Assembly Bill 617 (AB 617) on reducing air pollution and asthma disparities in disadvantaged communities. The research employs molecular biology techniques, including flow cytometry, proximity ligation assay, and RNA sequencing, to investigate IL-9 signaling in airway epithelial cells. It also involves a policy analysis of AB 617's initial effectiveness in reducing fine particulate matter (PM2.5) levels and asthmaassociated emergency room (ER) visits through environmental monitoring and hospital records. The study identifies a novel type II IL-9 receptor complex composed of IL-9Rα and IL-13Rα1, suggesting new therapeutic targets for asthma management. Policy analysis reveals limited initial success of AB 617 in reducing air pollution and asthma incidence, highlighting the need for enhanced regulatory measures and community engagement. Understanding the molecular mechanisms of IL-9 signaling and addressing environmental and social determinants are crucial for comprehensive asthma management. Integrating scientific research with policy interventions can improve health outcomes and reduce disparities in asthma prevalence and severity.
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Role of Tumor Oxygen Tension in Signaling and Response to Targeted Therapies
(2024-10) Adebayo, Adedeji Kolawole; Nakshatri, Harikrishna; Quilliam, Lawrence; Capitano, Maegan; Kim, Jaeyeon
Most tumor cells in solid tumors are exposed to oxygen levels ranging from 0.5% to 5%, but never to ambient air oxygen levels of about 21%. We developed an approach that allows collection, processing and evaluation of cancer and non-cancer cells under physioxia (3%-5% oxygen), ensuring little to no exposure to ambient air. This approach allowed for comparison of baseline and targeted therapy-induced changes in signaling pathways in cells under physioxia and ambient air and to identify potentially efficacious therapeutic combinations based on signaling pathways uniquely active under physioxia. Using tumor cells from two transgenic models of breast cancer and cells from breast tissues of clinically breast cancer-free women, we demonstrate oxygen level-dependent differences in cell preference for EGFR or PDGFRβ signaling. Physioxia caused PDGFRβ-mediated activation of AKT and ERK that reduced tumor cell sensitivity to EGFR and PIK3CA inhibition and maintained PDGFRβ+ epithelial-mesenchymal hybrid cells with potential cancer stem cell properties. Cells in ambient air displayed differential EGFR activation and were sensitive to EGFR and PIK3CA inhibition. Tumor cells grown under physioxia were sensitive to high affinity PDGFRβ inhibitor sunitinib. Furthermore, significantly higher synergistic growth inhibition and apoptosis was observed with lapatinib (a clinically used dual EGFR and ErbB2/HER2 inhibitor) and sunitinib combination only in tumor cells under physioxia both in vitro and in vivo. Our data emphasize the importance of oxygen considerations in preclinical cancer research to evaluate clinically relevant signaling pathways and identify novel drug targets or combination therapy approaches. We suggest that evaluation of candidate drugs for their efficacy under physiologic oxygen levels in preclinical models, prior to transitioning into clinical trials, would not only accelerate the development of effective drugs but also reduce failure at the clinical trial stage.
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A Glacier through a Grain of Sand: Sediment Micromorphology from a Land-Terminating Glacier in West Greenland
(2024-10) Woodie, Kayla Pearl; Licht, Kathy; Gilhooly, William P., III; Graly, Joseph
Isunnguata Sermia is a land terminating glacier in West Greenland with prominent upwellings of subglacial water in the outwash plain. Sediment that is suspended in the upwelling water is preserved in ice, creating a window into the subglacial environment. The presence of certain established microtextures, such as those caused by fluvial or high-stress processes, is indicative of a grain’s impact and transport history. Scanning electron microscopy (SEM) imaging of quartz sand grains is used to analyze this micromorphology. Across sand grains collected from different glacial depositional environments and the frozen subglacial water of Isunnguata Sermia, the microtexture distributions are extremely similar despite their different transport processes. While this may represent the limitations of microtexture analysis, it also suggests a high degree of sediment recycling in a basin that includes both the subglacial and the proglacial environment.