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    EXAMINING THE EFFECTS OF VIOLENCE EXPOSURE ON NEUROBEHAVIORAL DEVELOPMENT DURING EARLY ADOLESCENCE

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    Childhood exposure to violence is a global epidemic, affecting over one billion children annually. Early adolescence, a critical developmental stage, is marked by rapid changes. While the impact of violence on developmental outcomes has been extensively studied, understanding the precise pathways linking exposure to violence and neurobehavioral development remains limited. This study aimed to examine the effects of violence exposure on neurobehavioral development and the role of environmental factors in youth ages 9-10, using data from the Adolescent Brain and Cognitive Development (ABCD) Study. Participants (n=2420) with baseline violence exposure were followed for three years. Linear regression, mixed effects modeling, and multiple linear regression were used to assess the cumulative impact of violence on neurobehavioral development, the mediating role of brain connectivity, and the moderating effect of caregiver support. Results showed that internet victimization had persistent effects on brain communication. Cumulative violence exposure was linked to increased progression of brain communication between the Default Mode Network (DMN) and Salience Network (SN), as well as between the SN and Hippocampus. Additionally, several cortical network and subcortical region pairs were found to partially mediate the relationship between violence exposure and psychopathological outcomes. Notably, increased communication between the SN and Hippocampus partially mediated the link between violence exposure and both internalizing and externalizing symptoms. Lifetime exposure to witnessing violence influenced connectivity between the Frontoparietal Network and SN, with stronger effects in youth reporting low caregiver support and weaker effects in those with high caregiver support. Findings highlight how violence exposure alters brain communication across networks involved in emotional regulation, cognitive control, and threat detection, suggesting targeting these neural pathways could mitigate the mental health impact of violence. Violence exposure disrupts neural development, increasing the risk for psychopathology. Addressing violence exposure early is crucial to mitigating its long-term mental health impact. Pediatric primary care providers play a critical role in screening, evaluating, and addressing violence exposure in children and adolescents to promote healthy transitions into adulthood. Findings from this study support expansion of nursing practice to include comprehensive screening tools inclusive of various forms of violence encompassing both virtual and in person exposure. An interdisciplinary approach to understanding violence exposure’s impact on neurodevelopment and mental health, including collaborations across healthcare providers, will enhance the ability to develop targeted, effective treatments. Integration of these findings into nursing practice offers a holistic, translatable approach to care, positioning nurse clinician scientists to bridge the gap between research and practice, ultimately improving long-term outcomes for violence exposed youth

    THE THING WITH FEATHERS: ESSAYS AND STORIES ON THE ENVIRONMENT, ANIMALS, AND OUR CHANGING WORLD

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    In 1861, the young Emily Dickinson wrote, “Hope is the thing with feathers.” Quiet and daring, this line serves as a gentle reminder of the hope that resides in all of us, especially in times of political, societal, and ecological uncertainty. From climate change to cancer, articles and personal essays presented in this thesis examine our fragile ecosystems and existence. This thesis demonstrates how science can provide some answers but seems to harbor far more questions

    CHARACTERIZING DISTRIBUTION OF BODY MASS INDEX AND BLOOD PRESSURE OVER TIME (1997-2017) IN QIDONG, JIANGSU PROVINCE, CHINA

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    From 1990s to 2010s, China had experienced rapid economic development and urbanization, accompanied by dramatic dietary shift from traditional to more westernized diet, decreased physical activity and increased air pollution. We aimed to describe the body mass index (BMI), systolic blood pressure (SBP), and diastolic blood pressure (DBP) distributions among adults screened for clinical trials in Qidong, Jiangsu Province, China, between 1997 and 2017. Cross-sectional physical and clinical data from screenings for a series of 7 clinical trials were collected. Height, weight, and blood pressure were measured by trained personnel, and BMI was calculated from the formula: weight (kg) / height2 (m2). Participants were stratified by sex and age (60). Violin plots and cumulative distribution curves visualized trends in BMI, SBP, and DBP over time. Distributions were modeled using generalized gamma family, and the best-fitting distribution was selected. Relative percentiles of BMI, SBP, and DBP were compared (e.g. BMI quantiles for X year / BMI quantiles for reference year). Likelihood ratio test was used to compare each year’s distribution to the reference year to assess significance. Results showed an overall aging of the screened population. SBP increased substantially and consistently across different sex and age groups, particularly among those aged 50 and older. DBP also increased over time, but the trends were less consistent, with fluctuations over time and more variations by sex and age. BMI increased modestly across many subgroups, with the most noticeable rises among younger adults, especially women under 50. These findings reflect broader lifestyle and environmental transitions during China’s economic development and urbanization and highlight the growing burden of increased blood pressure and BMI in the urbanizing population. They underscore the need for targeted public health strategies to address the emerging cardiometabolic risks associated with rapid socioeconomic change

    Adaptation of Transposon-Sequencing Library Generation to Identify Colonization Genes in Animal Models of Candidiasis

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    Candida glabrata, the second leading cause of candidiasis infection, is an emerging pathogen with innate resistance to current frontline antifungals. The broad genetic variation, innate resistance profile, and our lack of mechanistic understanding of this strain necessitates further investigation into C. glabrata fitness and virulence pathways. Recent studies in C. glabrata use transposon sequencing (Tn-seq) in forward genetic screens to identify genes involved in drug resistance and pathogenicity. However, growth deficits in parent strains of existing models prevent complex and unbiased Tn-seq pools for host infection models. Here, a robust new method of Tn-seq in C. glabrata (now Nakaseomyces glabratus) using cycloheximide selection is established for use in host-colonization studies. This new method avoided parent strain growth deficits and successfully generated better enriched and more highly complex pools in multiple strains of C. glabrata than previous methods. With this new method, colonization genes can be studied in animal models with greater library depth than ever before. Further, colonization of new-method pools in the mouse gut allowed specific mechanistic comparison between CBS138 and BG2 reference strains in a host-infection model. This comparison revealed key differences in enriched gene insertion mutants between the two strains, highlighting the immense genetic variation in C. glabrata and the importance of clarifying divergent fitness mechanisms within reference strains of the species. Sequencing also identified commonly depleted gene-insertions in both BG2 and CBS138 pools, including phosphate homeostasis (PHO4, PHO84) genes. These conserved virulence-related genes could serve as promising new targets for future antimycotics

    The impact of xenobiotics on the gut microbiome, virome, resistome, and host health

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    Xenobiotics are compounds foreign to the human body, and include classes of molecules such as antimicrobials, supplements, and dietary additives, such as artificial sweeteners. Prior studies have suggested that antiretroviral therapy (ART) and non-nutritive sweeteners (NNS) may detrimentally impact cardiometabolic health, but the exact mechanism is unknown. Furthermore, in aerobic bacterial cultures, NNS have been observed to promote the transfer of antibiotic resistance genes, and exposure to antiretrovirals (ARVs) has induced phenotypic resistance and mutations conferring cross-resistance to antibiotics. The gut resistome is the reservoir of antibiotic resistance genes (ARGs) carried by commensal bacteria within the gut microbiome, which has been demonstrated to facilitate the emergence of antibiotic-resistant pathogens through horizontal transfer of ARGs from commensals. Our preliminary work shows an expansion of the gut resistome in mixed microbiome communities following NNS administration, as well as perturbances to the gut microbiome and virome following ART consumption. We hypothesize that NNS and ARVs alter the gut microbiome and resistome, resulting in cardiometabolic impairment and increased susceptibility to antibiotic-resistant pathogens. Using both computational and wet-lab based approaches, I investigated the impact of NNS on humans, and ARVs on mice and two complex microbiome communities in vitro under anaerobic conditions. The choice of analytical pipeline significantly impacted the outcome of resistome profiling, highlighting the importance of cross-validation. Nonetheless, this work provides evidence that ART may alter gut resistomes, impact bacterial growth in culture, impair glucose tolerance, and promote weight gain. Understanding how xenobiotics such as NNS and ART impact the microbiome and human health can provide valuable information to support efforts to limit the spread of antibiotic resistance and prevent the increasing trends in cardiometabolic syndrome

    ADVANCING THE UNDERSTANDING OF SWAGED STRUCTURAL REACTIVE MATERIALS: A COMPREHENSIVE STUDY OF MECHANICAL PROPERTIES, FRAGMENTATION, AND PERFORMANCE

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    This dissertation explores the microstructure, mechanical properties, and fragmentation of swaged structural reactive materials, with a particular focus on aluminum as a model system. The study aims to advance the understanding of these materials by examining their mechanical properties and behavior under various conditions, utilizing innovative techniques such as rotary infeed swaging and ballistic launch studies. The research begins with a comprehensive review of the current state of structural reactive materials, highlighting their potential applications in defense and other industries. The methodology section details the experimental setup, including the rotary infeed swaging process and the ballistic launch apparatus used to simulate real-world impact conditions. A key aspect of this work is the characterization of the materials' microstructures, performed using Scanning Electron Microscopy (SEM) and micro–Computed Tomography (micro-CT or µCt). These techniques provide detailed insights into the internal structures and help in understanding the correlation between microstructure and material performance. The results demonstrate significant findings in the mechanical properties of swaged aluminum, including its strength and ductility at quasi-static strain rates and its fragmentation patterns under high-strain-rate conditions. The analysis of fragmentation and performance metrics reveals critical aspects of material behavior, offering valuable data for future material design and application. Moreover, the study discusses the influence of the swaging process on the material's microstructure, linking specific microstructural features to observed performance outcomes. Despite the constraints imposed by the sensitivity of some data, this dissertation contributes to the field by providing a broad understanding of the fundamental properties and potential of structural reactive materials. The findings have implications for the development of advanced materials with tailored properties for specific applications. Future research directions include exploring other high-density reactive systems and further refining characterization techniques to enhance the understanding of these complex materials

    HUMAN CELL BASED MODEL TO ASSESS THE IMPACT OF DEVELOPMENTAL IMMUNOTOXICANTS ON BRAIN DEVELOPMENT

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    In recent decades, the number of people diagnosed with neurodevelopmental disorders (NDDs) has increased dramatically (Shaw, 2025). Genetic factors have been investigated, but fail to explain all NDD diagnoses (Grandjean, 2014; Shelton, 2014). New research aims to explore non-genetic, environmental exposures that may hinder neuronal development as a potential contributor to NDDs. Data suggests toxicant exposures might deleteriously affect the developing immune and nervous systems (Sotgiu, 2020). Epidemiological studies have linked maternal immune dysregulation with altered neurodevelopment (Han, 2021). However, there remains a need for human models to understand the mechanisms of these connections better. In this project, we have developed a novel approach to characterize how inflammation from developmental immunotoxicity affects neurodevelopment. Human monocyte-derived macrophages (hMDMs) were differentiated in the presence of environmentally relevant toxicant exposures. Chemicals analyzed include lead (Pb) as lead (II) acetate trihydrate, dexamethasone (DEX), tributyltin oxide (TBTO), and chlorpyrifos (CPF). Lipopolysaccharide (LPS) was also used in combination with toxicant exposures to activate an inflammatory response (Park, 2013). Supernatants from exposed and activated macrophages were then introduced to brain organoid cultures to simulate systemic neuroinflammation. Following a 72-hour exposure, neurite outgrowth was measured by fluorescent microscopy. We found that brain organoids exposed to supernatant from macrophages treated with TBTO significantly increased neurite complexity compared to controls containing either 50% macrophage media, 100% organoid media, or direct TBTO organoid exposures (adjusted P= 0.0036, 0.0133, 0.0040, respectively). We also found that supernatants from macrophages treated with DEX significantly increased neurite outgrowth compared to macrophages stimulated with LPS following exposure to DEX (adjusted P=0.0141). More data is needed to conclusively say whether the exposures impede or enhance the growth of neurites. This model has the potential to provide a holistic understanding of the causes of neurodevelopmental disorders by investigating the effects of systemic immunotoxicity on brain cultures. Future research investigating proinflammatory molecules expressed by hMDMs and their respective molecular pathways is needed to elucidate the synergistic relationship between the immune and nervous systems. Further understanding of these pathways will allow for advancements in diagnoses, legislation, and treatment for individuals affected by neurodevelopmental disorders

    Paper Tigers: Deconstruction and Semiotics of Gender Equity as Signifier in Water Governance Policies — A Case Study in Ghana

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    A “paper tiger” refers to something that appears threatening or powerful but lacks real strength or effectiveness—it seems formidable, nonetheless is fundamentally weak. Ghana's 2015 Gender Equity Bill, while a significant step toward addressing gender disparities, has been criticized as a “paper tiger” for its lack of enforceability and tangible impact. This study examines gender equity in water governance and gender equity policies in Ghana, focusing on the gap between policy discourse and structural outcomes. Using a mixed-methods approach—including a cross-regional survey (N = 100), expert interviews, and deconstructive analysis of policy texts—the research finds that women's inclusion is symbolic rather than substantive. Although 59% of male and 41% of female respondents identified women’s underrepresentation as a major governance barrier, 17% of relevant policies lack enforceable gender equity mechanisms. Framed by Kanter’s theory of tokenism, the theory of gender politics, and Derrida’s Deconstruction, the study introduces the concept of the “paper tiger” policy: documents that perform equity through language while deferring real structural change. Deconstruction exposes how signifiers like “empowerment” obscure exclusion through euphemism and technocratic abstraction. The research recommends including parliamentary seat rotation and institutional reform. It contributes a new method of applying Deconstruction and Semiotics to governance, centering language as a site of power and exclusion

    SCIENTIFIC APPROACHES TO SUICIDE RESEARCH WITH THE U.S. MUSLIM COMMUNITY: PILOT PHASE FINDINGS OF U.S. MUSLIM COMMUNITY STUDY OF MENTAL HEALTH

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    Objectives: The study aimed to examine suicidality and psychosocial factors in U.S. Muslims: 1) Quantitatively assess psychosocial variables associated with suicidality among U.S Muslims. 2) Qualitatively explore community-specific risk and resilience factors; and 3) Develop prevention strategies by partnering with Community Based Organizations (CBOs). Background: Suicide is a leading cause of death globally, yet arguably the most preventable of all health outcomes. In Muslim-majority countries, suicide attempt behaviors and fatality rates are underreported in data due to judicial, social, and religious norms. Research shows Muslims in the United States report twice the lifetime attempt rates compared to other faith groups, yet epidemiological data on Muslim identity and health behaviors remains absent from national databases in the Global North. Methods: Employing Community-Based Participatory Research (CBPR), this cross-sectional, multi-method study engaged three different Muslim-serving CBOs. Using Qualtrics, an anonymous online survey collected data from January 2023 to February 2024 through snowball recruitment (N=111 participants). Participants met the eligibility criteria of: identifying as Muslim currently or formerly, living in the U.S. for at least 1 year, and adults aged 18 or older. Quantitative measures included an augmented Suicide-Behaviors Questionnaire-Revised (SBQ-R), an adapted Stigma Consciousness Scale (SCS-M), the Challenged Sense of Belongingness (CSB) scale, an adapted Psychological Acculturation Scale, and the Lifetime Discrimination scale. Statistical analyses involved descriptive statistics, correlation, and linear regression, with adjustments for nativity, education, and age. Qualitative data were collected though six open-ended qualitative questions that explored potential risk (e.g., hopelessness, ingroup discrimination) and resilience factors of suicide (e.g., safe space guidelines, connectedness) through a lived experience perspective. Results: A total of N=111 self-reporting participants remained, with a retention rate close to 80%. Sixty-four percent of participants (64%) reported a lifetime history of ideation, or a previous suicide attempt, with 44.1% reporting future desire to attempt suicide. Linear regression analyses (N=70; adjusted R2=0.534), revealed significant positive associations between suicidality and lifetime discrimination (p<0.001), followed by a challenged sense of belongingness (p=0.001), and psychological acculturation (p<0.05). Stigma consciousness of Muslim identity did not associate significantly with the outcome at an a=0.05 cutoff (p=0.232). Qualitative findings indicated themes of: social and mental health determinants, religious and community factors, family conflict and intimate partner factors, gender norms and identity challenges, emotional factors and trauma/abuse, political events and overall health factors. Resilience factors revealed needs for ground rules, professional resources, social support, religious approaches, diverse leadership, inclusive attitudes, shared identity experiences, and culturally relevant affirmations. Conclusion: The pilot study suggests that there may be homophily dynamics in suicide transmission within the U.S. Muslim community, and discrimination is a critical factor associated with suicidality. The findings provide a foundation for community-led intervention guidelines for public health suicide prevention and culturally relevant strategies that promote life-affirming values within the U.S. Muslim community

    THE PROTON-ACTIVATED CHLORIDE CHANNEL: A REVIEW OF FORM AND FUNCTION AND SPECIFIC ROLES IN THE CENTRAL NERVOUS SYSTEM

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    The transport of ions through cellular membranes is essential for life and is achieved by ion transporters that are usually specific for one type of ion. Of known ion channels, cation-specific channels are disproportionally better characterized than anion channels. Due to this, the understanding of anion homeostasis, particularly of chloride, has lagged despite their important roles in the cell. Chloride is involved in maintaining electrostatic balance, cell excitability, acid/base homeostasis, cell volume regulation, and many other functions. Thus, discovering and understanding the roles of novel chloride channels is physiologically important. We provide a comprehensive review of what is known about the proton-activated chloride (PAC) channel (encoded by PACC1 or TMEM206) from multiple studies that have been published since the cloning of the channel in 2019. Insights into its trimeric structure, proton-sensing, inactivation mechanism, and lipid regulation are discussed. PAC also has a newly discovered function as an endosomal chloride channel that maintains pH balance. This has functional significance in various cellular contexts, such as receptor trafficking and phagosome/macropinosome maturation. PAC is highly enriched in the brain. The role of PAC in neurons is explored in-depth, with the finding that PAC is involved in neurotransmitter receptor trafficking during synaptic plasticity. Synaptic plasticity entails long-term potentiation (LTP) and long-term depression (LTD), or the activity-dependent strengthening and weaking of synapses, respectively. This has been proposed to be the mechanistic basis of cognitive processes such as learning and memory and is shown to depend on endosomal PAC channel. Mice with neuron-specific PAC deletion had impaired hippocampal LTD and performed poorly in the Morris water maze reversal test, which assesses behavioral adaptation. PAC is also highly expressed in microglia, the resident immune cells of the brain. PAC notably participates in phagosome acidification and cellular uptake of amyloid β, which forms pathogenic protein aggregates in Alzheimer’s disease. PAC has important roles in broad cellular contexts. Specifically in the central nervous system, regulation of vesicular chloride and pH homeostasis have emerged as important players in endocytic processes that support neuronal and microglial function

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