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A Lockean Theory of Intuition
No full textThis dissertation attempts to extract a Lockean theory of general intuitions from Locke’s various commitments. It starts by identifying the intentional object of Lockean intuitions based on his ontological commitments. This is followed by a characterization of the mental content of Lockean intuitions and their relations to their representata and subjects. Finally, it identifies the nature of Lockean general intuitions based on previous considerations and Locke’s position on knowledge and judgment. It argues that the intentional objects of general intuitions are abstract ideas, which are also the mental content of general intuitions. These conclusions, in addition to Locke’s position on knowledge and judgment, support the view that the Lockean theory of general intuitions is nominalist naïve realism.</p
Impact of Maternal Factors on Infant Immunity to BCG and TB
No full textInfants from high Tuberculosis (TB) burden settings have a higher risk of exposure to Human Immunodeficiency Virus (HIV) and latent TB infection (LTBI) in utero. Whether or not exposure to HIV and TB in utero influences the development of infant immunity is unclear. Therefore, we investigated the effects of LTBI exposure in HIV-exposed uninfected infants on Mycobacterium tuberculosis (Mtb)-specific antibody levels and function, phenotypic profiles of immune subsets, and the proliferation and functional capacity of T cell responses to Bacille Calmette-Guérin (BCG) vaccine and Mtb-specific antigens. Frozen plasma and peripheral blood mononuclear cells (PBMC) from 199 pregnant women living with HIV and their infants were studied from the IMPAACT P1078 clinical trial. Mothers and infants were assessed for LTBI via the interferon gamma release assay (IGRA). 6 mothers progressed to possible, probable, or confirmed active TB (ATB). We revealed that antibody functional responses were impaired in the context of HIV/TB coinfection. Progression to ATB in mothers was marked by reduced lipoarabinomannan (LAM)-specific antibodies and enhanced Mtb-specific phagocytosis. This data also revealed that exposure to LTBI in utero influenced functional antibody and T cell responses with exposed infants demonstrating a Th1-dominated response to BCG. Further analysis of infants who became IGRA+ at 44 weeks showed that IGRA+ infants had enhanced Mtb-specific phagocytosis, similar to TB progressors, while T cell responses to BCG were dominated by a suboptimal Th17 response when compared to IGRA- infants. In utero exposure to LTBI results in immune alterations that mimic a classic TB response potentially indicating the presence of in utero sensitization. However, it is unclear if immune priming is beneficial to infants in the first year of life. While this research provides evidence of the short-term impact on in utero exposure to LTBI, further studies are warranted to understand the impact of these changes in the long term and whether these infants are more or less likely to develop TB as they age.</p
Estimating Aerosol-Derived Phosphorus and Iron Fluxes to the Surface Ocean: Looking Beyond Mineral Dust to Understand the Aerosol Indirect Effect on Biogeochemical Cycles
No full textWhile many factors affect climate via impacts on radiative forcing, the magnitude of impacts associated with aerosol-related processes remains the most uncertain. Two mechanisms through which aerosols impact radiative forcing have been considered in climate models and projections for decades. However, a third mechanism, the “aerosol indirect effect on biogeochemical cycles,” has only been considered in the last 15 years. This mechanism describes aerosols’ ability to impact atmospheric carbon dioxide concentrations via releasing nutrients that stimulate photosynthetic growth and/or nitrogen fixation upon deposition. For example, in the North Atlantic Ocean, mineral dust deposition releases significant amounts of phosphorus (P) and iron (Fe), which stimulate phytoplankton production, nitrogen fixation, and carbon dioxide drawdown. However, we lack definitive estimates for P and Fe bioavailability in mineral dust, and little is known about nutrient release from other aerosol types like volcanic ash. My work shows that P solubility in mineral dust deposited in the North Atlantic has declined since the 1990s due to air pollution regulations like the Clean Air Act. I also demonstrate that volcanic ash, in addition to mineral dust, can serve as a source of soluble and bioavailable P to seawater. Finally, Fe in mineral dust is nearly 10% bioavailable to marine phytoplankton, while Fe in volcanic ash is only about 6% bioavailable. I show that aerosol mineralogy and interaction with acidity prior to deposition are the dominant factors controlling aerosol Fe bioavailability. My work provides evidence that atmospheric aerosols besides mineral dust provide important fluxes of soluble and bioavailable nutrients to the North Atlantic Ocean, and the relative importance of non-dust aerosol in this region is likely increasing with air quality regulations that have reduced nutrient solubility in mineral dust.</p
Identifying Predictors of Withdrawal of Life-Sustaining Therapies in Acute Brain Injury at a Level I Trauma Center
No full textBackground: Withdrawal of life-sustaining therapy (WLST) decisions in acute brain injury (ABI) remain complex and variable, with limited data on predictors in Level I trauma centers. This study examines sociodemographic and clinical factors influencing WLST decisions for adults with ABI.Methods: This retrospective cohort study analyzed data from adults with ABI admitted to the Neuroscience ICU at Jackson Health System from June 2020 to January 2025. Mann-Whitney U and Chi-square tests were used to compare continuous and categorical variables, respectively, between WLST and non-WLST patients. Univariate (UVA) and multivariate (MVA) binary logistic regression models were used to explore the relationship between WLST and age, Charlson Comorbidity Index (CCI), Glasgow Coma Scale (GCS), and pupillary reactivity. Bonferroni correction was appplied to address multiple comparisons across all statistical analyses. Crude (OR) and adjusted odds ratios (aOR) were reported with corresponding 95% confidence intervals (95% CI) to quantify associationsResults: Among 127 participants, most were male (81.1%), White (67.7%), or privately insured (38.6%). In total, 22.8% of patients (n=29) underwent WLST; this group was significantly older (pConclusion: The single-center study provides insight into WLST decisions for adults with ABI at a Level I trauma center. Our results align with aggregated data from diverse centers and registries, and the recognition of age as a predictor of WLST, supporting the importance of adjusting for age in clinical decision-making and the need for standardized, patient-centered, and equitable approaches to WLST.</p
Further Characterization of the Affective Itch Circuit in Mice
No full textThe central amygdala (CeA) is known to be highly involved in mediating itch and anxiety, but the pathways and mechanisms are yet to be fully understood. The goal of this project was to further study two subsets of the neuronal population within the parabrachial nucleus (PBN)-CeA pathway. The first population is itch-responsive PBN neurons, which project to the CeA. These neurons were captured using the targeted recombination in active populations system and were activated using optogenetic stimulation. I found that activating these neurons could cause an increase in spontaneous scratching, but caused no change in pruritogen induced scratching, anxiety-like behaviors, or pain-like behaviors. Additionally, I found that inhibiting these neurons in a chronic itch model could decrease the amount of spontaneous scratching but did not change anxiety-like behaviors. The second population of neurons are CeA neurons that express neuropeptide y receptor 2. When activated with optogenetics, these neurons had a significant decrease in pruritogen induced scratching behaviors, but no change in anxiety-like behaviors or pain-like behaviors. Overall, I found that these two subsets of the neuronal population within the PBN-CeA pathway seem to be itch specific but have opposite effects on itch behavior when activated. Further research is necessary to fully understand how they interact with each other in the itch affective circuit.</p
Advanced Heterogeneous Recurrence Analysis of Complex Spatial Temporal Dynamics with Biomedical Applications
No full textModern healthcare increasingly relies on analyzing biomedical sensor data, yet modeling such data is difficult because many physiological systems exhibit nonlinear, nonstationary behaviors. Classical time- and frequency-domain methods support many applications but assume linearity or stationarity but miss the nonlinear dynamics driving complex physiological processes. Deep learning can capture such patterns, but its dynamic representations are opaque and offer limited interpretability. Recurrence analysis (RA), grounded in nonlinear dynamics, provides an alternative by tracing returns in state-space to reveal periodic, intermittent, and chaotic behaviors. However, existing RA approaches underrepresent heterogeneity across modalities and scales, insufficiently capture within- and cross-dynamic variability, and impose heavy computational burdens due to pairwise state comparisons.This dissertation advances a recurrence-based framework that addresses these challenges in three parts. (1) Advanced Dynamic System Characterization: heterogeneous recurrence analyses for quantifying nonlinear dynamics in spatial and spatiotemporal systems. (2) Rapid Recurrence Quantification: a deep-learning-aided surrogate that amortizes pairwise comparisons to enable near-real-time RA. (3) Quantification-Guided High-Fidelity Synthesis: a conditional generative model constrained by recurrence structure to produce faithful, controllable signals for augmentation, evaluation, and robustness testing.Together, these methods capture nonlinear and nonstationary dynamics, account for heterogeneous modalities and scales, and deliver calibrated, interpretable metrics. They support diagnosis and prognosis, enable real-time monitoring, and help reveal disease mechanisms. Recurrence-constrained synthesis enhances robustness and efficiency through data augmentation. Overall, this framework offers a principled, interpretable foundation for modeling complex biomedical systems and bridging nonlinear dynamics with clinical translation.</p
Navigating Sexuality and Resilience: A Multi-Method Study on Black Queer Women Living With HIV
No full textThis study investigates the evolving nature of sexuality among Black women living with HIV (BWLWH) and explores how Black queer women in this population experience and cope with microaggressions. Black queer women living with HIV (BQWLWH) experience numerous oppressive systems in their day-to-day life, including but not limited to racism, sexism, HIV-related stigma, homophobia, classism, and ableism. However, there is little literature on the impact of intersectional marginalization on the mental and HIV-related health outcomes of BQWLWH. Qualitative interviews were administered to further discuss the role of structural oppression, coping mechanisms, and resilience strategies that BQWLWH have utilized to navigate systems of oppression. Additionally, a quantitative analysis was utilized to understand how sexuality changes over time for BWLWH and how various factors (e.g., education, income, microaggression) impact and influence identity synthesis and acceptance. For the qualitative component, a thematic analysis was utilzed to interpret data and identify recurring patterns and themes (n = 20). For the quantitative component, it was analyzed using Generalized Estimating Equations (GEE; n = 260). This study’s findings reveal the complex, intersecting challenges faced by BQWLWH, including frequent experiences of racism, sexism, homophobia, and HIV-related stigma. These forms of discrimination - anticipated, enacted, and internalized - were linked to psychological distress but also prompted adaptive coping, particularly through faith and spirituality. While quantitative data showed stability in sexual identity over time, qualitative accounts highlighted fluidity and evolution in participants’ self-identification. Participants shared experiences of exclusion from families, healthcare, and both Black and LGBTQ+ communities, yet also described resilience through reflection, spirituality, and advocacy. These results underscore the need for trauma-informed, culturally responsive interventions that support the well-being and agency of BQWLWH.</p
Deep Learning for Predicting Cancer Prognosis
No full textAccurate cancer prognosis is critical for personalized treatment but remains challenging due to high-dimensional, heterogeneous biomedical data and limited sample sizes. This dissertation proposes a novel deep learning framework integrating supervised contrastive learning (CL) and a semi-supervised mean-teacher model, both optimized for survival prediction via the Cox proportional hazards loss.First, we apply supervised CL to whole-transcriptome gene expression data across 19 cancer types from The Cancer Genome Atlas (TCGA). This approach yields compact, biologically meaningful embeddings that significantly enhance the concordance index (c-index) and risk stratification compared to traditional methods. Notably, the model exhibits robust out-of-distribution generalization on external CPTAC and DKFZ cohorts without retraining.To improve robustness and leverage unlabeled data, we introduce a semi-supervised mean-teacher architecture. By enforcing student-teacher consistency using the proposed Cox loss, this approach achieves a increase in c-index over supervised baselines. Incorporating a large unlabeled external BRCA cohort further elevates the TCGA BRCA prognostic c-index to 0.89.The framework is subsequently extended to multimodal analysis by integrating diagnostic whole-slide images (WSIs). We developed a pipeline to automatically segment tumor regions and encode features using pre-trained models, including ResNet and DINOv2. These WSI features are fused with genomic data via a mutual attention mechanism, yielding an additional 5% improvement in the c-index over the unimodal model.This dissertation presents a unified semi-supervised, multimodal framework that synergizes gene expression and imaging data. The resulting methods and open-source tools establish a scalable foundation for next-generation precision oncology, effectively bridging advanced deep learning with clinical practice.</p
Reprogramming the Epigenome of (Pre)malignant Hematopoietic Cells with Retinoic Acid and Ascorbate
No full textEnhancing TET2 activity through genetic or pharmacologic approaches, such as ascorbate supplementation, can slow myeloid malignancy progression. However, ascorbate alone may be insufficient to fully activate TET2 in malignant cells due to pharmacokinetic constraints and the need for chromatin remodeling to enable effective epigenetic reprogramming. Here, we identify a novel mechanism to enhance TET2 activity via all-trans retinoic acid (ATRA), which induces RARA-mediated TET2 transcription in myeloid leukemia cells and synergizes with ascorbate to promote DNA hydroxymethylation and chromatin remodeling at key myeloid differentiation loci. Using Tet1/2/3-deficient mice and primary human AML models, we show that ATRA plus ascorbate more effectively induces differentiation, inhibits leukemia stem cell self-renewal in a TET2-dependent manner, and sensitizes AML cells to targeted therapies in vivo leading to improved survival. These findings support the combined use of ATRA and ascorbate as a strategy to enhance TET2 activity for the treatment of myeloid malignancies.</p
Intergenerational and Cultural Drivers of Depressive Symptoms in Hispanic Sexual Minority Youth
No full textAdverse childhood experiences (ACEs) are traumatic events occurring within the first 18 years of life. ACEs disproportionately impact Hispanic individuals compared to their non-Hispanic White counterparts. These early adversities are associated with long-term negative effects on mental health and impaired parenting behaviors that can transmit risk across generations. As such, the elevated burden of parental ACEs within Hispanic communities may be a contributing factor to persistent mental health disparities among Hispanic youth. This risk may be especially pronounced among Hispanic sexual minority youth (HSMY), who face higher rates of depressive symptoms relative to their nonHispanic White peers and who may be burdened by both ethnic and sexual minority stressors. This dissertation’s purpose will be to: (1) examine the relationship between parental ACEs and youth depressive symptoms, (2) determine whether acculturation differences between caregivers and their youth and the sexual minority identity of the youth affect this relationship, and (3) explore how marginalized identities may intersect with cultural values and contribute to depressive symptom development among HSMY. This study will use secondary data from samples of HSMY and Hispanic non-SMY and primary data from qualitative interviews with HSMY to accomplish its purpose. </p