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In Vitro Characterization And Evolution Of Sylvatic And Endemic Dengue-4 Viruses, Andrew Peric

Yale Graduate School of Arts and Sciences Dissertations

Dengue virus is the world’s preeminent arthropod-borne virus that infects hundreds of millions of people each year, and circulates in four distinct serotypes named 1, 2, 3, and 4. Dengue virus cycles between mosquito and human hosts in a transmission cycle called the endemic cycle, which is responsible for the majority of recorded dengue infections worldwide. However, dengue also exists in a second transmission cycle called the sylvatic cycle, which mirrors the endemic cycle with wildlife, including non-human primates, replacing humans in this transmission cycle. Phylogenetic analyses support the hypothesis that spillover events from the sylvatic cycle into human populations …

West From West Point: The U.S. Military Academy And The Romantic Frontier, Ryan Shaw

Yale Graduate School of Arts and Sciences Dissertations

This dissertation examines the influence of Romanticism on the culture and curriculum of the United States Military Academy in the early nineteenth century, and demonstrates how it shaped the behavior of U.S. Army officers on the far western frontier. While historians have long associated Romanticism with the frontier experience, it has traditionally been framed as an output, rather than an input. This study identifies West Point as an unexpected but significant source of Romantic ideals.

The history of the Academy is presented uniquely here as a contest between three competing visions: A republican ideal of a modest military …

Insights Into How A C. Elegans Neural Circuit Transitions Between Two Internal States To Produce Egg-Laying Behavior, Shavanie Prashad

Yale Graduate School of Arts and Sciences Dissertations

A challenge in neuroscience is understanding how neural circuits generate and sustain behavior over time. Neural circuits consist of interconnected groups of neurons that process and integrate sensory information to perform specific tasks and behaviors. These circuits organize behaviors by maintaining internal states—stable neural activity patterns influenced by sensory and physiological contexts, as discussed in Chapter One.

To understand how neural circuits generate internal states, we examined how the well-characterized C. elegans egg-laying circuit transitions between inactive and active states to produce egg-laying behavior. The active internal state lasts approximately 2 to 3 minutes, during which one or more eggs …

Identifying How Pseudomonas Aeruginosa Cells Become Primed For Expression Of Type Iii Secretion System Genes, Kristen Alicia Ramsey

Yale Graduate School of Arts and Sciences Dissertations

Pseudomonas aeruginosa is an opportunistic pathogen known to cause acute infections in individuals with epithelial damage or medically placed devices, leading to sepsis or death in immunocompetent and immunocompromised individuals. Like many other Gram-negative bacteria, P. aeruginosa uses a Type III Secretion System (T3SS) to intoxicate eukaryotic cells. This T3SS is essential for P. aeruginosa to establish an infection and avoid clearance by immune cells and is also linked to increased morbidity and mortality in infections. Despite this necessity, activation of the T3SS slows P. aeruginosa’s cell growth and permits innate immune system detection and resulting inflammation. To balance …

Development Of Genome-Scale Technologies For Writing And Recoding Cyanobacteria, Laura Beth Quinto

Yale Graduate School of Arts and Sciences Dissertations

Diverse microorganisms have delivered unique solutions in medicine, food, energy, and nutrient cycling through atmospheric gas fixation. Yet despite tremendous progress in model organisms like E. coli and S. cerevisiae, tools for editing and predictably manipulating undomesticated species – which comprise the vast majority of microbes1 – remain scarce. Cyanobacteria, with their light- and CO₂-powered metabolism, hold particular promise for bioproduction, bioremediation, and in situ fertilization, but have been difficult to engineer. Furthermore, many of the most valuable applications of cyanobacteria would involve implementation in an open system. Such strains require two critical safeguards: biocontainment to ensure that their propagation …

A Hierarchical Bayesian Meta-Regression Model For Incorporating Exposure Range Variability, Xiaotong Xu

Public Health Theses

Accurately synthesizing evidence from epidemiologic studies is essential for understanding complex environmental risk relationships and establishing causal relationships. However, the majority of meta-analyses in this area ignore the possibility of variability in risk due to differences in study-specific exposure levels while typical dose-response statistical methods assume a single dose amount per study and not a distribution or range of doses (i.e., exposures). We develop a novel hierarchical Bayesian meta-regression framework that incorporates functional averaging over study-specific exposure ranges and models the underlying exposure-response relationship using a flexible Gaussian process. Using a low-rank predictive process formulation, our approach efficiently projects functional …

Enhancing Dengue Forecasting With Remotely Sensing-Derived Vector Proxies And Random Forest Models: A Case Study For Sri Lanka, Shuyu Ye

Public Health Theses

Dengue fever is a growing global public health threat, especially in tropical and subtropical regions such as Sri Lanka, where seasonal outbreaks impose recurring burdens on health systems. Accurate and timely forecasting of dengue incidence is essential for public health preparedness, yet most existing models suffer from key limitations: they rely on historical case trends without accounting for real-time ecological dynamics, and often require entomological surveillance data that is not consistently available. This thesis addresses these gaps by proposing a machine learning forecasting framework that integrates remote sensing-derived environmental proxies to estimate latent mosquito vector abundance.Using Principal Component Analysis (PCA), …

The Prescription Drug User Fee Act (Pdufa): The Design, Evolution, And Challenges Of User Fees And The Reauthorization Process, Therese Ziaks

Public Health Theses

The Prescription Drug User Fee Act (PDUFA) has had a critical role in funding the Food and Drug Administration (FDA) through the form of industry user fees since 1992 with user fees comprising 48% of the FDA’s Fiscal Year 2024 budget. As the FDA faced pressure from Congress and the pharmaceutical industry to reduce drug application review times, the legislation was enacted to provide a funding source in addition to Congressional appropriations so the agency could meet proposed review time goals. As the FDA began to hire additional review staff, reduce application review times, and increase the number of pharmaceuticals …

Dnabert Reveals Tf Motifs Information In Dna With Attention, Zetong Zhao

Public Health Theses

Traditional motif discovery tools often do not capture cooperative interactions between transcription factors (TFs). This study employs DNABERT, a transformer-based deep learning model, to analyze TF binding sites (TFBS) using attention mechanisms and k-mer tokenization. Fine-tuned on ENCODE ChIP-seq data, DNABERT achieved high predictive accuracy and could identify co-binders such as FOS and JUND through motif enrichment analysis. The model inferred position weight matrices (PWMs) aligning with JASPAR motifs and highlighted the regulatory importance of sequences near gene start regions. Comparisons with BPNet showed strong correlations, which validated DNABERT’s ability to capture TF-specific patterns. While constrained by dataset biases and …

Evaluating The Impact Of P. Falciparum Genetic Diversity On Pfrh5 Blood Stage Vaccine Protection Through A Multi-Method Approach, Alyssa Agarwal

Public Health Theses

Malaria remains a major global health threat as control efforts have stalled in recent years. Recently, theWHO began recommending two vaccines, RTS,S/AS01 and R21, both of which target the pre-erythrocytic stage of malaria. However, these vaccines are only partially protective and do not protect against the blood-stage of malaria where clinical disease begins. Therefore, a more broadly protective vaccine is still needed. Plasmodium falciparum reticulocyte-binding protein homolog 5 (PfRH5) is a leading candidate for next-generation blood-stage malaria vaccines with the most advanced formulation, RH5.1/Matrix-M, recently entering Phase 2b clinical trials. However, historically, malaria vaccine development has been challenged by the …

Period Poverty And The Politics Of Refusal: Building Menstrual Equity Beyond The State Through Mutual Aid, Alanah Armstead

Public Health Theses

This thesis examines period poverty as a consequence of systemic neglect, disproportionately affecting those made vulnerable by intersecting structures of racial, gendered, and economic injustice. Situating menstruation as a public health crisis shaped by policy failure, social stigma, and institutional disregard, this research critiques dominant legal and policy frameworks that approach menstrual equity through a limited scope that overlooks deeper structural inequalities rooted in race and class. This thesis explores how marginalized populations experience legal and welfare systems as sites of surveillance and moral judgment in the context of menstrual equity. Through seven semi-structured interviews with menstrual justice organizers, this …

Cost-Effectiveness Of New Monoclonal Antibody And Maternal Immunization For The Prevention Of Respiratory Syncytial Virus (Rsv) Disease In Infants: A Systematic Review, Yuwei Che

Public Health Theses

AbstractIntroduction: Respiratory syncytial virus (RSV) remains a major cause of morbidity and mortality among infants and young children worldwide. Given the lack of specific therapeutic treatments for RSV that are suitable for universal use, the development of effective prevention strategies is of paramount importance. Previously, palivizumab was utilized for long-term prophylaxis of RSV infections; however, it was only recommended for specific populations due to its high cost and limited overall effectiveness. In 2023, the U.S. FDA approved RSVpreF maternal vaccine (Abrysvo™, Pfizer), and nirsevimab (Beyfortus™, Sanofi and AstraZeneca) for the prevention of RSV to newborns. Two newly developed interventions have …

Assessing Impact Of Maternal Proximity To Unconventional Oil And Gas Wells On Neonatal Birthweight In Ohio: A Retrospective Cohort Study (2010–2017), Alan Cao

Public Health Theses

AbstractBackground: Unconventional oil and gas development (UOGD) has expanded rapidly in the United States, particularly in states like Ohio, which is home to approximately 5,000 horizontal shale wells and more than 80,000 hydraulically fractured wells since 1952. Although oil and gas extraction has occurred in Ohio for over 60 years, the recent surge in UOGD activity has raised renewed public health concerns about environmental exposures during pregnancy. While previous studies have linked maternal proximity to UOGD with adverse birth outcomes, evidence remains limited regarding its association with birthweight and fetal growth indicators in high-production states such as Ohio.

Methods: We …

The Impact Of Climate Change On Japanese Encephalitis Trends In China, Jiayi Du

Public Health Theses

Japanese encephalitis (JE) is a mosquito-borne viral disease that poses a significant public health threat across Asia, including China. Climate change has been increasingly recognized as a key driver of JE transmission dynamics, influencing mosquito vector distribution and virus proliferation. This study aimed to assess how climatic variables affect the ecological suitability for Japanese encephalitis virus (JEV) transmission, using species distribution modeling with MaxEnt.

Using climate data from WorldClim and JE incidence data from published sources, we applied the MaxEnt model to identify the key environmental predictors of JE transmission and project future risk areas under changing climatic conditions. The …

Evaluating Clinical Outcomes And Cost-Effectiveness Of Aspirin And Clopidogrel Versus Factor Xa Inhibitors And Clopidogrel For Treatment Of Patients With Peripheral Arterial Disease After Lower Extremity Revascularization, Uday Dhanda

Public Health Theses

Introduction and Objective: Antithrombotic treatment plays a critical role in managingperipheral arterial disease (PAD) and reducing the risk of major adverse limb events (MALE) and major adverse cardiovascular events (MACE) after revascularization. Dual antiplatelet therapy (DAPT) with aspirin and clopidogrel is the most commonly used regimen for medical management to prevent cardiovascular events following revascularization. Still, emerging studies suggest that dual antithrombotic pathway inhibition (DAPI), which combines a Factor Xa inhibitor with clopidogrel, may offer enhanced protection. This study evaluates the clinical outcomes and cost-effectiveness of DAPI compared to DAPT in patients undergoing lower extremity revascularization (LER).

Methods: A retrospective …

Secondhand Smoke Exposure And The Risk Of Tuberculosis In Children: A Systematic Review And Meta-Analysis, Cenyun Guan

Public Health Theses

ABSTRACT

Introduction: Tuberculosis (TB) remains one of the leading causes of death globally, with children and young adolescents having a significant burden of the disease. Smoking is a well-established risk factor for TB, but the association between secondhand smoke (SHS) exposure and TB remains inconclusive. Pediatric populations are commonly exposed to SHS due to living with smokers in their households. Inconsistencies in the findings of previous systematic reviews on the associations between SHS exposure and TB status (infection and disease) highlight the need for an updated systematic review to better establish these associations and provide evidence-based guidance for reducing the …

Swift: Strong-Signal Weighted Prs Integration For Fine-Tuning, Yikai Dong

Public Health Theses

Polygenic risk scores (PRS) hold immense promise for personalized medicine but suffer from reduced accuracy in non-European populations, hindering equitable application. We introduce SWIFT (Strong-signal Weighted PRS Integration for Fine-Tuning), a novel framework to enhance cross-population PRS prediction by optimally combining base scores from diverse ancestries using only GWAS summary statistics. SWIFT employs a GWAS subsampling technique based on data fission to generate internal training and tuning sets, circumventing the need for external validation cohorts. A key innovation is its focus on strong genetic signals (p < 0.1) for estimating robust combination weights via cross-validation, which mitigates overfitting and significantly reduces computational burden. We evaluated SWIFT across 22 complex traits using data from five populations (EUR, AFR, AMR, EAS, SAS) and independent validation cohorts (UK Biobank, All of Us). Applied to state-of-the art base methods (PRS-CSx, X-Wing, JointPRS), SWIFT achieved predictive accuracy comparable or superior to the recent LEOPARD integration method and baseline implementations. Crucially, SWIFT demonstrated a 3.5- to 9.5-fold reduction in computational runtime compared to LEOPARD and exhibited robust performance even when using a single, unified LD reference panel. SWIFT provides an efficient, robust, and practical approach to improve the accuracy and applicability of PRS across diverse populations, representing a significant step towards more equitable genomic medicine.

Present Tense Love: How To Stay Close Amidst A Changing Mind, Brit Fleck

Public Health Theses

This thesis examines how long-term partners sustain intimacy when one partner lives with dementia. Through an Appreciative Inquiry (AI) workshop with four couples from the Empowering Partnership Network—a joint initiative of the Yale Social Gerontology Lab and the Livewell Institute—this research explores how relationships adapt and endure amidst cognitive change. Drawing on Irene Smith’s Touch Awareness methodology and theories of relational autonomy, the study challenges dominant deficit-based narratives by highlighting the enduring capacity for meaningful connection. Participants described intimacy as grounded in embodied practices, daily rituals, and what they called the “third body”—a shared relational space that transforms rather than …

Comparative Effectiveness Of Digital Breast Tomosynthesis And Digital Mammography In Detecting Invasive Lobular Carcinoma And Smaller Tumors Among Older Women, Sida Huang

Public Health Theses

AbstractBackground: Digital breast tomosynthesis (DBT) has demonstrated improved cancer detection and reduced false-positive and recall rates compared with digital mammography (DM) alone in trials of women aged over 50. However, its benefits for older women remain uncertain. We hypothesized that among women aged 67+, breast cancer detected via DBT are more likely to be invasive lobular carcinoma (ILC) and present at a smaller size at diagnosis, and this association persists among women aged 75+. Additionally, we hypothesized that DBT detects ILC at a smaller tumor size. Methods: We conducted a retrospective cohort study of women aged 67+ with screen-detected ER+/HER2- …

Cost-Effectiveness Of Active Surveillance, Radical Prostatectomy, And Radiotherapy For Patients With High-Risk Non-Metastatic Prostate Cancer, Nathan Lai

Public Health Theses

Background: Current standards of care guide patients with high-risk prostate cancer (T3a or Gleason score 8–10 or PSA >20 ng/ml) toward treatment options such as radical prostatectomy (RP), or radiotherapy (RT) regardless of their life expectancy. These interventions are often invasive, costly, and may offer limited benefit compared to active surveillance (AS). While previous cost-effectiveness analyses have established that active surveillance in low-risk prostate cancer patients (T1–T2a, Gleason score ≤6, and PSA <10 ng/ml) is a cost-effective initial strategy, its role in the management of high-risk patients, especially those with limited life expectancy, remains unclear. This study aims to extend previous cost-effectiveness modeling to the high-risk population to inform decision makers on the most appropriate strategy of care considering a 10-year time horizon.

Methods: This retrospective cost-effectiveness cohort study using the Veterans Affairs Cohort Study (VACS) dataset, which contain electronic health records of men with high-risk prostate cancer. Patients included in …

The Evolution And Effectiveness Of Sterile Insect Technique For Vector Control: A Historical And Modern Analysis, Katerina Karaiskos

Public Health Theses

Sterile Insect Technique (SIT) has emerged as an important tool in the control of vector-borne diseases, providing an alternative to traditional chemical insecticides. Initially based on the irradiation of insects to induce sterility, SIT has proven effective in eradication campaigns, including the cases of the screwworm and tsetse fly. SIT’s primary strengths lie in its species specificity, environmental safety, and the avoidance of pesticide resistance. However, “classic” irradiating SIT is limited by high operational costs, reduced mating competitiveness of sterilized males, and difficulties in addressing high-density vector populations. Recent advancements in genetic-based SIT methods, such as the Release of Insects …

Assessing The Cross-Species Vaccine Potential Of Pfripr Using Transgenic Chimeric Plasmodium Knowlesi Models, Peiqi Li

Public Health Theses

Malaria remains a major global health burden, with an estimated 263 million cases and597,000 deaths reported in 83 countries in 2023 (1). While P. falciparum is responsible for the most severe cases, non-falciparum species such as P. vivax, P. ovale curtisi, P. ovale wallikeri, P. malariae, and P. knowlesi also pose significant public health risks, particularly in co-endemic regions. Current malaria vaccine efforts mainly focus on P. falciparum which is reasonable because over 90% of the global malaria-related morbidity and mortality are caused by P. falciparum (2). However, laying emphasis on targeting P. falciparum leaves a critical gap in cross- …

Prevalence And Correlates Of Antipsychotic Use Without An Indicated Diagnosis Among Long-Stay Residents In Nursing Facilities In Massachusetts, Hongyi (Sophie) Liu

Public Health Theses

Background: In 2012, the Centers for Medicare & Medicaid Services (CMS) implemented initiatives to reduce unnecessary antipsychotic medication use in elderly nursing home residents to ensure quality of care. While antipsychotic use among long-stay nursing home residents has decreased nationwide, Massachusetts still exceeds the national average and ranks 6th in the U.S. This study aims to evaluate and identify both facility-level characteristics and resident-level correlates of antipsychotic use without an indicated diagnosis among long-stay residents in Massachusetts nursing homes. Methods: The study examined 30,857 long-stay residents across 345 nursing facilities in CY2023, using data from the Minimum Data Set (MDS), …

Global Perspectives On 1,4-Dioxane: Environmental Persistence, Detection Strategies, And Policy Frameworks, Haoyu Lyu

Public Health Theses

1,4-Dioxane is a persistent environmental contaminant present in industrial activities, pharmaceutical manufacturing, and consumer items, particularly challenging to manage due to its high solubility in water and resistance to traditional water treatment processes. Although some countries have implemented stringent regulatory measures, there is a lack of consistent detection and remediation of 1,4-Dioxane in the environment, potentially leading to unregulated contamination in areas with insufficient monitoring capabilities.

In this literature review, studies that have already been published focusing on 1,4-dioxane pollution in China, South America (including Brazil, Argentina, and Peru), and Europe (Germany and the Netherlands) will be evaluated against relevant …

Joint Realities: Prevalence, Frequency, And Modality Of Cannabis Use By Sexual Identity In A Multi-State Brfss Sample (2022–2023), Meredith Audrey Rose Mcgee

Public Health Theses

Cannabis use has increased substantially among U.S. adults, yet disparities by sexual orientation and sex remain underexplored, particularly regarding frequency and consumption modality (Hammond et al., 2022; Dyar, 2022). Leveraging 2022–2023 Behavioral Risk Factor Surveillance System (BRFSS) data from eight U.S. states, this study examined patterns of past-month cannabis use among U.S. adults, stratified by sexual orientation–sex group (e.g., bisexual women, gay men).Guided by minority stress theory and prior research (Dyar, 2022; Meyer, 2003; Poole et al., 2021; Schofield et al., 2023), we hypothesized that sexual minority adults, especially bisexual individuals across both sexes, would report: (1) higher prevalence of …

Stage-Specific Disruption Of Cancer Cell Metabolism By Pfas: Connecting “Forever Chemicals” To The Growing Public Health Challenge Of Colorectal Cancer, Hannah O'Halloran

Public Health Theses

Per and polyfluoroalkyl substances (PFAS), termed “forever chemicals” for their persistence in the environment, are under investigation for their carcinogenic effects, but their specific impacts on colorectal cancer (CRC) progression remain largely unexplored. This study uses untargeted metabolomics to examine the effects of PFAS exposure on cells of CRC stages 2, 3, and 4, and identify state-specific alterations in important metabolic pathways. Later stage cells exhibit a greater response than early stage cells, suggesting increased susceptibility to PFAS effects in cells of more advanced cancer. PFOS had a greater effect on the metabolism of the cell lines compared to PFOA, …

Characterizing The Genetic Diversity Of Pfrh5 In Plasmodium Falciparum Clinical Isolates From Burkina Faso, Ghana, And Tanzania: A Next-Generation Sequencing Study To Inform Blood-Stage Malaria Vaccine Development, Manuel Emilio Perez

Public Health Theses

The development of a highly effective malaria vaccine is of global health priority, given the persistently high malaria burden in Sub-Saharan Africa (SSA) and growing resistance to antimalarial treatment and vector control measures. P. falciparum reticulocyte-binding protein homolog 5 (PfRH5) has emerged as a leading target among blood-stage malaria vaccine candidates due to its essential role in erythrocyte invasion and initial documentation of limited polymorphisms. However, recent studies have revealed greater PfRH5 genetic diversity than previously believed, raising concerns about potential parasite evasion of vaccine-induced immunity. This study utilized deep targeted amplicon next-generation sequencing to characterize PfRH5 genetic variation in …

From Success To Setbacks: A Case Study Of The Sex Wrap And The Impact Of Instagram's Evolving Policies On Sexual Health Education, Megan Piller

Public Health Theses

Due to the inconsistent and noncomprehensive nature of sexual health education across the United States, many adolescents and emerging adults are turning to digital platforms, specifically social media, for necessary information. The Sex Wrap (TSW), a podcast and Instagram-focused intervention, was established to fill critical knowledge gaps among these populations and empower them in their sexual decision-making. To serve as a case study, engagement metrics from TSW’s Instagram account between October 2020 and September 2021 were analyzed to determine which post types, tones, and thematic categories resonated most with users across the platform. However, Instagram, once a highly effective tool …

Global Comparison Of Children’S Exposomes, Inumidun Oyebode

Public Health Theses

Environmental influences impact health, often with enhanced susceptibility for theyoung. Understanding the sources of these environmental factors is critical for mitigating exposures. Globally, children are exposed to many sources that differ by policy, urbanization, and socioeconomic conditions. Specifically, urbanization creates variation in exposure sources that differ in rural (refuse combustion, cooking biomass combustion, indoor residual spray) and urban areas (vehicle combustion, industrial activity). Differences in policy further shape these exposure patterns by regulating pollution sources, chemical use, and environmental protections across countries. This thesis evaluated environmental exposures of children living in United States, South Africa, and Singapore contributing to a …

Liver Epigenetic Changes In Mice Exposed To 1,4-Dioxane In The Drinking Water: Implications For 1,4-Dioxane Liver Carcinogenicity, Shuya Qiao

Public Health Theses

1,4-Dioxane, a probable human carcinogen and widespread environmental contaminant, has been consistently associated with liver tumor development in rodents. However, limited research has addressed its role in epigenetic dysregulation. This study investigated epigenetic alterations in liver tissue following chronic exposure to 1,4-dioxane. Male mice of wild-type (WT) and glutamate-cysteine ligase modifier subunit knockout (Gclm-KO) genotypes were exposed to 0, 50, or 500 ppm of 1,4-dioxane in drinking water for six months. qPCR, Western blotting, and immunohistochemistry (IHC) were used to assess changes in DNA methylation-related enzyme gene expression, histone acetylation, and SAM (S-adenosylmethionine) distribution. qPCR results showed significant downregulation of …