3,392 research outputs found

    Undergraduate Catalog of Studies, 2023-2024

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    Graduate Catalog of Studies, 2023-2024

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    Neuromodulatory effects on early visual signal processing

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    Understanding how the brain processes information and generates simple to complex behavior constitutes one of the core objectives in systems neuroscience. However, when studying different neural circuits, their dynamics and interactions researchers often assume fixed connectivity, overlooking a crucial factor - the effect of neuromodulators. Neuromodulators can modulate circuit activity depending on several aspects, such as different brain states or sensory contexts. Therefore, considering the modulatory effects of neuromodulators on the functionality of neural circuits is an indispensable step towards a more complete picture of the brain’s ability to process information. Generally, this issue affects all neural systems; hence this thesis tries to address this with an experimental and computational approach to resolve neuromodulatory effects on cell type-level in a well-define system, the mouse retina. In the first study, we established and applied a machine-learning-based classification algorithm to identify individual functional retinal ganglion cell types, which enabled detailed cell type-resolved analyses. We applied the classifier to newly acquired data of light-evoked retinal ganglion cell responses and successfully identified their functional types. Here, the cell type-resolved analysis revealed that a particular principle of efficient coding applies to all types in a similar way. In a second study, we focused on the issue of inter-experimental variability that can occur during the process of pooling datasets. As a result, further downstream analyses may be complicated by the subtle variations between the individual datasets. To tackle this, we proposed a theoretical framework based on an adversarial autoencoder with the objective to remove inter-experimental variability from the pooled dataset, while preserving the underlying biological signal of interest. In the last study of this thesis, we investigated the functional effects of the neuromodulator nitric oxide on the retinal output signal. To this end, we used our previously developed retinal ganglion cell type classifier to unravel type-specific effects and established a paired recording protocol to account for type-specific time-dependent effects. We found that certain retinal ganglion cell types showed adaptational type-specific changes and that nitric oxide had a distinct modulation of a particular group of retinal ganglion cells. In summary, I first present several experimental and computational methods that allow to study functional neuromodulatory effects on the retinal output signal in a cell type-resolved manner and, second, use these tools to demonstrate their feasibility to study the neuromodulator nitric oxide

    UMSL Bulletin 2023-2024

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    The 2023-2024 Bulletin and Course Catalog for the University of Missouri St. Louis.https://irl.umsl.edu/bulletin/1088/thumbnail.jp

    Graduate Catalog of Studies, 2023-2024

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    Life on a scale:Deep brain stimulation in anorexia nervosa

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    Anorexia nervosa (AN) is a severe psychiatric disorder marked by low body weight, body image abnormalities, and anxiety and shows elevated rates of morbidity, comorbidity and mortality. Given the limited availability of evidence-based treatments, there is an urgent need to investigate new therapeutic options that are informed by the disorder’s underlying neurobiological mechanisms. This thesis represents the first study in the Netherlands and one of a limited number globally to evaluate the efficacy, safety, and tolerability of deep brain stimulation (DBS) in the treatment of AN. DBS has the advantage of being both reversible and adjustable. Beyond assessing the primary impact of DBS on body weight, psychological parameters, and quality of life, this research is novel in its comprehensive approach. We integrated evaluations of efficacy with critical examinations of the functional impact of DBS in AN, including fMRI, electroencephalography EEG, as well as endocrinological and metabolic assessments. Furthermore, this work situates AN within a broader theoretical framework, specifically focusing on its manifestation as a form of self-destructive behavior. Finally, we reflect on the practical, ethical and philosophical aspects of conducting an experimental, invasive procedure in a vulnerable patient group. This thesis deepens our understanding of the neurobiological underpinnings of AN and paves the way for future research and potential clinical applications of DBS in the management of severe and enduring AN

    Multidisciplinary perspectives on Artificial Intelligence and the law

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    This open access book presents an interdisciplinary, multi-authored, edited collection of chapters on Artificial Intelligence (‘AI’) and the Law. AI technology has come to play a central role in the modern data economy. Through a combination of increased computing power, the growing availability of data and the advancement of algorithms, AI has now become an umbrella term for some of the most transformational technological breakthroughs of this age. The importance of AI stems from both the opportunities that it offers and the challenges that it entails. While AI applications hold the promise of economic growth and efficiency gains, they also create significant risks and uncertainty. The potential and perils of AI have thus come to dominate modern discussions of technology and ethics – and although AI was initially allowed to largely develop without guidelines or rules, few would deny that the law is set to play a fundamental role in shaping the future of AI. As the debate over AI is far from over, the need for rigorous analysis has never been greater. This book thus brings together contributors from different fields and backgrounds to explore how the law might provide answers to some of the most pressing questions raised by AI. An outcome of the Católica Research Centre for the Future of Law and its interdisciplinary working group on Law and Artificial Intelligence, it includes contributions by leading scholars in the fields of technology, ethics and the law.info:eu-repo/semantics/publishedVersio

    Redefining Disproportionate Arrest Rates: An Exploratory Quasi-Experiment that Reassesses the Role of Skin Tone

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    The New York Times reported that Black Lives Matter was the third most-read subject of 2020. These articles brought to the forefront the question of disparity in arrest rates for darker-skinned people. Questioning arrest disparity is understandable because virtually everything known about disproportionate arrest rates has been a guess, and virtually all prior research on disproportionate arrest rates is questionable because of improper benchmarking (the denominator effect). Current research has highlighted the need to switch from demographic data to skin tone data and start over on disproportionate arrest rate research; therefore, this study explored the relationship between skin tone and disproportionate arrest rates. This study also sought to determine which of the three theories surrounding disproportionate arrests is most predictive of disproportionate rates. The current theories are that disproportionate arrests increase as skin tone gets darker (stereotype threat theory), disproportionate rates are different for Black and Brown people (self-categorization theory), or disproportionate rates apply equally across all darker skin colors (social dominance theory). This study used a quantitative exploratory quasi-experimental design using linear spline regression to analyze arrest rates in Alachua County, Florida, before and after the county’s mandate to reduce arrests as much as possible during the COVID-19 pandemic to protect the prison population. The study was exploratory as no previous study has used skin tone analysis to examine arrest disparity. The findings of this study redefines the understanding of the existence and nature of disparities in arrest rates and offer a solid foundation for additional studies about the relationship between disproportionate arrest rates and skin color

    Idiopathic inflammatory myopathies and cancer : familial risk, genetics and consequences

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    Idiopathic inflammatory myopathies (IIMs) are a group of rare rheumatic inflammatory diseases (RIDs), characterised by a diverse range of clinical, serological and histopathological characteristics, with muscle weakness as a shared hallmark. While advancements in disease management have improved the survival rates of patients with IIM, the mortality rate among patients with IIM is still higher than the general population, mainly due to association with comorbidities such as cancer. The pathogenesis of IIM, the pathological link between IIM and cancer and the impact of cancer on the survival of patients with IIM remain a subject of uncertainty. The rarity and heterogeneity inherent in IIM pose significant challenges in filing these knowledge gaps. This thesis encompasses five studies, which aimed at addressing research questions concerning the genetic contribution to IIM and its link with other autoimmune diseases and cancer, as well as the disease burden in the context of cancer in a large representative population of patients with IIM. Study I was a population-based case-control family study including 7,615 first-degree relatives of 1,620 patients with IIM diagnosis between 1997 and 2016 and 37,309 first-degree relatives of 7,797 matched comparators without IIM. Patients with IIM were four times more likely to have at least one first-degree relative affected by IIM compared to matched comparators without IIM. The heritability of IIM, a proportion of the phenotypic variance that can be explained by additive genetic variance, was 22% in the Swedish population. Study II, with the same study population as in Study I, analysed the familial associations between IIM and a variety of autoimmune diseases under a causal framework. We found shared familial factors between IIM and other RIDs, inflammatory bowel diseases, autoimmune thyroid diseases and celiac disease. Study III, with a similar study population and analytical approach as in Study II, comprehensively investigated the familial co-aggregation of IIM and cancer. We did not observe a familial association between IIM and cancer overall but modification effect by sex was noted: there was a modest familial association (adjusted odds ratio=1.39) with cancer in male first-degree relatives of patients with IIM. We also found that offspring of patients with IIM were more likely to have a cancer diagnosis at age younger than 50 years compared to those of matched comparators without IIM. In the exploratory analysis by specific cancer types, findings suggest that IIM shared familial factors with myeloid malignancies and liver cancer. Study IV explored genetic correlation between IIM and B-cell lymphomas via a cross-trait secondary analysis using summary statistics from genome-wide associations studies of IIM and four common B-cell lymphoma subtypes including diffuse large B-cell lymphoma, follicular lymphoma, chronic lymphocytic leukaemia and marginal zone lymphoma. We detected a limited number of genomic loci, predominantly within the human leukocyte antigen region, demonstrating significant genetic correlations between IIM and common Bcell lymphoma subtypes. Study V, a cohort study, followed 1,826 patients to (first and second) cancer and death (overall and cause-specific death) events since IIM diagnosis for more than 20 years. Compared to patients with no cancer diagnosis after IIM, patients with a first cancer diagnosis after IIM faced a greater five-year mortality (22% versus 49%). This excessive risk was due to an increased risk of death from cancer. In patients with a first cancer diagnosis after IIM, the one-year risk of having a second primary cancer was 11% and having a second cancer diagnosis slightly increased the risk of death. We also reported several prognostic factors associated with increased risks of cancer and death (overall, from cancer and from other causes). This thesis offers useful insight into the role of genetics in IIM pathogenesis and its connections with other autoimmune diseases and cancer, as well as the impact of cancer on the survival of patients with IIM. The observed familial aggregation of IIM and familial associations between IIM and other autoimmune diseases suggest genetic involvement in the development of IIM. Family history of IIM, other RIDs, inflammatory bowel diseases, autoimmune thyroid diseases and celiac disease may serve as indicators pointing towards an IIM diagnosis. Missing heritability is suggested by the discrepancy between our family-based heritability and the SNP-based heritability, implying yet-to-be discovered genetic variants associated with IIM. The acquired knowledge of shared familial factors between IIM and other autoimmune diseases may inform future genetic studies aiming to uncover novel IIMassociated genetic variants. There is a limited shared familial/genetic susceptibility between IIM and cancer. The human leukocyte antigen region plays an important role in the limited shared genetic susceptibility between IIM and common B-cell lymphoma subtypes. IIM concomitant with cancer leads to a substantial increase in mortality, mainly due to cancer. Future research should focus on reducing cancer-related disease burden in patients with IIM

    UMSL Bulletin 2022-2023

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    The 2022-2023 Bulletin and Course Catalog for the University of Missouri St. Louis.https://irl.umsl.edu/bulletin/1087/thumbnail.jp
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