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Repurposing Ezetimibe As A Therapeutic For Parkinson's Disease: Evaluating The Therapeutic Potential And Probing For A Mechanism, Brian Hilton

Yale Medicine Thesis Digital Library

Neurologic disease is the leading cause of disability globally and Parkinson’s disease (PD) has been the fastest growing neurologic brain disease over the last several decades. Despite the immense burden of PD on patients and society, there has yet to be an efficacious disease-modifying therapy. Investigation of candidate pharmaceuticals that have already been approved by the FDA for other conditions might provide an expedited path to the advent of disease-modifying therapy. There is a rich history of drug repurposing for symptomatic therapy for PD, with amantadine as the preeminent example. In order to identify candidate therapeutics for possible repurposing, an …

Rns-Based Early Prediction Of Antiseizure Medication Efficacy, Joshua Hobbs

Yale Medicine Thesis Digital Library

Drug-resistant focal epilepsy accounts for a significant portion of patients with epilepsy. These patients many times experience persistent seizures despite several ASM (anti-seizure medication) trials. RNS (Responsive neurostimulation) has demonstrated efficacy in reducing seizure frequency in patients that are resistant to drug trials, and provide continuous intracranial electroencephalographic monitoring. This longitudinal data may offer an opportunity to identify potential early biomarkers of ASM trial effectiveness, which could lead to quicker optimization of pharmacological therapy. This study in particular evaluated whether early changes in RNS-detection of seizure activity can predict a clinical response to ASMs in patients with drug-resistant focal epilepsy. …

Associating Inflammatory Dermatoses And Gynecological Disorders Using The National Institutes Of Health’S All Of Us Research Program, Christine Myriam Hodelin

Yale Medicine Thesis Digital Library

There remains a gap in the knowledge about the relationship between inflammatory disorders and common gynecological disorders, despite significant quality of life concerns for both. We examined the association between hidradenitis suppurativa (HS) and endometriosis, and the association between atopic dermatitis (AD) and uterine leiomyomas, both with a cross-sectional study using electronic health record and survey data from the National Institutes of Health’s All of Us Research Program.

The All of Us Research Program has a large United States-based cohort and focuses on traditionally underrepresented populations in research. We compared cases and controls, all assigned female at birth, using Pearson’s …

A Spatial Transcriptomic Atlas And Cellular Lineage-Based Analysis Of Chondroblastoma, Will Jiang

Yale Medicine Thesis Digital Library

Chondroblastoma is a benign primary bone tumor with controversial cellular origin. Although bearing the name “chondroblastoma”, this musculoskeletal tumor has faced controversy as to whether chondroblasts are chondrocytes. Moreover, its cellular composition can make it difficult to distinguish amongst its mimics including giant cell tumor of bone, chondrosarcoma, and chondromyxoid fibromas.

This thesis aims to characterize the transcriptomic expression atlas of human chondroblastoma to better define the gene expression profile and diagnostic expression markers of chondroblastoma. Secondarily, this thesis aims to identify the lineage progression and cellular composition of chondroblastoma using spatial and temporal patterning analysis.

Histologically confirmed samples of …

Trends, Predictors, And Cerebrovascular Outcomes Of Vertebral Artery Injury In Cervical Fractures, Rahul Jayaram

Yale Medicine Thesis Digital Library

Background and Scientific Premise: Cervical spine trauma is a common emergencydepartment presentation, and vertebral artery injury (VAI) is a potentially occult but serious complication associated with posterior circulation stroke. Identification of patients at risk remains challenging due to subtle presentations, variable screening practices, and limited prior data. Research Aims: The aims of this study were to characterize temporal trends in VAI detection among adult patients presenting to the emergency department with cervical spine fractures between 2010 and 2022, identify independent demographic, clinical, and injury-related predictors of VAI, and evaluate the association between VAI and ischemic stroke within ninety days of …

Prevalence, Predictors, And Consequences Of Postoperative Dysphagia After Aortic Surgery, Andrew Joseph Johnson

Yale Medicine Thesis Digital Library

Prevalence, Predictors, and Consequences of Postoperative Dysphagia After Aortic SurgeryAndrew Johnson and Ronny Munoz-Acuna, M.D., Department of Anesthesiology, Yale School of Medicine, New Haven, CT 06510. Abstract Background: Postoperative dysphagia is an underrecognized complication following cardiothoracic surgery and is associated with aspiration, prolonged hospitalization, and adverse clinical outcomes. Patients undergoing complex aortic surgery may be at particularly high risk due to prolonged mechanical ventilation, extensive airway instrumentation, and neurologic vulnerability. Data describing the prevalence, predictors, and clinical consequences of postoperative dysphagia in this population remain limited. Research Aim: This study consisted of three aims: first, to determine the prevalence and …

Frailty And Functional Decline After Elective Endovascular Abdominal Aortic Aneurysm Repair, Judy Li

Yale Medicine Thesis Digital Library

Background: Frailty can be used to estimate perioperative and long-term mortality risk in octogenarians undergoing elective endovascular abdominal aortic aneurysm repair (EVAR). Its association with functional decline, an important surrogate of quality of life in older adults, has not been well studied in this population. We aimed to evaluate whether preoperative factors such as frailty are associated with one-year functional decline after elective EVAR in octogenarians and to compare the performance of three different frailty assessments.

Methods: The Vascular Quality Initiative (VQI) database was queried for octogenarians who underwent elective EVAR for an asymptomatic infrarenal abdominal aortic aneurysm (AAA) (2014 …

Economic Development And The Environment, Kelsey Jack, Nicholas Ryan

Discussion Papers

Economic development relies on and transforms the environment. The transformation is evident in the poor environmental quality in many developing countries. For example, air quality in Southeast Asia is three times worse than in the United States, in sub-Saharan Africa four times worse and in South Asia more than six times worse. We model how environmental quality affects health, productivity and well-being and how individuals privately adapt to environmental hazards. We also model how collective action and formal regulation contribute to environmental quality. We draw three main findings from a review of empirical research on these mechanisms. First, individual adaptation …

How Wasteful Is Signaling?, Alex Frankel

Cowles Foundation Discussion Papers

Signaling is wasteful. But how wasteful? We study the fraction of surplus dissipated in a separating equilibrium. For isoelastic environments, this waste ratio has a simple formula: β/(β + σ), where β is the benefit elasticity (reward to higher perception) and σ is the elasticity of higher types’ relative cost advantage. The ratio is constant across types and independent of other parameters, including convexity of cost in the signal. A constant waste ratio characterizes the isoelastic class. In winner-take-all signaling tournaments with N candidates, exactly (N − 1)/N of the surplus dissipates—the same as in Tullock contests.

Using Oyster Genomics To Understand Human Health, Walker Daniel Bargmann

Public Health Theses

As sessile filter feeders that experience continuous environmental exposure, oysters—particularly Crassostrea virginica—offer a unique opportunity to understand how environmental exposure alters the genome and influence health. Furthermore, oysters must be sorted by size for market value for premium size and taste. However, it requires intensive labor, specialized equipment (tumblers), and is susceptible to environmental risks like pollution. Therefore, it is desirable to produce uniform oysters without machines. However, limitations in the previous reference genome [2] have constrained our understanding of how genes are organized and maintained in oyster populations. To this end, we harvested 240 adult oysters in same location, …

Implementation Of Digital Interventions To Address Alcohol Use In Primary Care: A Scoping Review, Sean Becker

Public Health Theses

The development and implementation of digital interventions in the identification andmanagement of unhealthy alcohol use (i.e., the spectrum of consumption including at-risk alcohol use and alcohol use disorder) in the primary care setting has seen numerous advancements in recent years. Such rapid change makes it difficult to understand and assess the current state of the literature as it relates to these implementation topics. To better understand the broader research landscape, we (SB, Advised by EJE and BK and with collaboration from AG) conducted a scoping review to: 1) characterize the focus, components, and mode of digital interventions for targeting alcohol …

Black Carbon Exposure And Adult Mental Health And Cognitive Function: A Scoping Review, Zhihong Cai

Public Health Theses

Background: Black carbon (BC) is a particulate matter component that is closely linked to combustion and traffic sources, serving as both a short-lived climate pollutant and a potential risk factor for brain health. Despite a substantial burden of adult mental health disorders and cognitive decline, epidemiological evidence on BC exposure and brain health remains scattered.Objective: To systematically map study types, main findings, evidence gaps, and methodological limitations regarding BC exposure and its proxy indicators, such as PM₂.₅ absorbance and elemental carbon in relation to mental health and cognitive outcomes in adults. Methods: Following PRISMA-ScR guidelines, I searched PubMed, Web of …

Sex Differences In Metabolic Pathways Of Colorectal Cancer Liver Metastases, Yunhan Chen

Public Health Theses

Background: Colorectal cancer liver metastasis (CRLM) is a major cause of death in colorectal cancer, and growing evidence suggests that sex may influence tumor biology and metabolism. However, sex-specific metabolic changes in CRLM remain poorly understood.Method: This study performed sex-stratified metabolomics analysis of CRLM tissue samples using datasets generated from HILIC and RPLC LC-MS acquisition modes. Differential metabolites were identified using Wilcoxon tests with FDR correction, and pathway enrichment analysis was conducted using MetaboAnalyst to compare shared and sex-specific metabolic patterns between male and female samples. Results: Both male and female CRLM samples showed metabolic alterations in shared pathways, including …

Discrimination And Stress Recovery In Romantic Couples: A Dyadic Analysis Of Vagal Rebound And Stress Appraisal, J. Doris Chi

Public Health Theses

Background: Perceived discrimination is a chronic stressor linked to adverse psychological and physical health outcomes, yet less is known about how it shapes parasympathetic recovery after acute stress within close relationships. The present study examined the direct and vicarious effects of discrimination on vagal rebound and stress appraisal following a social-evaluative speech task, and whether these associations varied by identity attribution.

Methods: Data were drawn from 188 romantic couples (N = 376) from the New Haven area. Participants completed measures of everyday discrimination prior to the laboratory visit and stress appraisal before and after the speech task. Respiratory sinus arrhythmia …

Intergenerational Meaning-Making In Cambodian Americans, Caitlin Gojuk

Public Health Theses

Background: Cambodian Americans face high psychological distress yet remain underrepresented in research, especially second-generation individuals. Intergenerational trauma, stigma, and family dynamics shape mental health understanding and expression. Objective: This study examines how Cambodian American young adults make sense of mental health and distress through cultural identity, family relationships, and inherited meanings of trauma. Methods: In-depth semi-structured interviews were conducted with six second-generation Cambodian American young adults residing in Massachusetts, United States. Participants completed brief measures of depression and anxiety symptoms (PHQ-8; GAD-7) to provide a descriptive context. Interviews were analyzed using inductive thematic analysis informed by relational, narrative, and ecological …

A Mendelian Randomization Study Of Maternal Thyroid Function And Cerebral Palsy, Yuewen Ge

Public Health Theses

Cerebral palsy (CP) is a neuromotor disorder that is strongly associated with adverse perinatal conditions. Thyroid dysfunction in pregnancy was suggested to affect CP risk in a few cohort studies, but the evidence is not yet conclusive. We conducted a two-sample MR study to explore the effect of thyroid function on the risk of CP in offspring, and preterm birth as a potential mediator. Genetic instruments for hyperthyroidism and hypothyroidism were obtained from a large European genome-wide association study (GWAS) by Sakaue et al. (2021), instruments for free thyroxine (FT4) and thyrotropin (TSH) were derived from the ThyroidOmics Consortium, and …

Cost-Effectiveness Analysis Of Twice-Yearly Injectable Lenacapavir Versus Daily Oral Prep For Hiv Prevention Among Men Who Have Sex With Men In China, Xueqing Guo

Public Health Theses

Men who have sex with men (MSM) remain a key at-risk population in China’s HIV epidemic while the real-world effectiveness of daily oral pre-exposure prophylaxis (PrEP) among MSM has been limited by low uptake and suboptimal drug adherence. Lenacapavir, a first-in-class capsid inhibitor administered twice yearly, emerged as a highly efficacious, long-acting prevention strategy with the potential to reduce drug burdens associated with current PrEP strategy. However, its high price ($28,000 per patient per year) raises major affordability concerns, and its economic value in China remains understudied. This study aimed to evaluate the cost-effectiveness of lenacapavir compared with daily oral …

Single-Cell Gene Perturbation Prediction Via Sclambda-Program, Jingyi Guo

Public Health Theses

Predicting single-cell transcriptomic responses to single and multi-gene perturbations is essential for mapping regulatory networks, resolving disease mechanisms and identifying therapeutic targets. Several state-of-the-art deep learning methods, especially scLAMBDA, have demonstrated strong performance in predicting perturbation outcomes. However, computational biology still faces a fundamental trade-off between predictive accuracy and biological interpretability. To reconcile these objectives, there is an urgent need to develop models that can generate accurate perturbation predictions and simultaneously uncover distinct functional pathways. Thus, we introduce scLAMBDA-Program, a novel deep generative variational autoencoder framework that builds upon the robust predictive foundation of the scLAMBDA architecture. scLAMBDA-Program incorporates a …

Water Resource Governance And Health Equity In Angola, Mads Harner

Public Health Theses

AbstractBackground: Angola is confronting a set of intertwined challenges including water insecurity, increasing climate variability, and deep structural inequality that together intensify the burden of waterborne and water-related diseases (Lombana Cordoba et al., 2021; World Health Organization, 2025). Roughly half of the population does not have reliable access to safe drinking water, and gaps in sanitation and hygiene infrastructure, especially in peri-urban and rural areas, facilitate the spread of illnesses such as cholera, diarrheal diseases, and malaria (UNICEF Angola, 2025; Moreira et al., 2012). These issues are further exacerbated by drought and broader climate variability, and underlying them are historical …

Family-Related Stressors And Mental Health Among Internally Displaced Young Adults In Mozambique: A Mixed-Methods Study With Implications For Global Mental Health Interventions, Jaspreet Kandola

Public Health Theses

Mental health outcomes among displaced populations are shaped by post-displacement stressors, yet the role of family dynamics, specifically, remains insufficiently understood. This study examines how family-related stressors are associated with mental health among internally displaced young adults in Nampula Province, Mozambique. Using a convergent parallel mixed methods design, this study integrated survey data from 601 participants with qualitative data from in-depth interviews with a subsample of 16 participants. Quantitative analyses showed that family separation and concern for family members in conflict zones were associated with higher posttraumatic stress disorder (PTSD) symptoms, with family separation also linked to higher anxiety and …

Nowcasting Dengue Cases In Poor Surveillance Nations Using Meteorology And Climate-Similar Countries, Hanna Kim

Public Health Theses

Dengue fever poses a growing public health burden across the Caribbean, yet surveillance infrastructure remains inconsistent and timely outbreak detection in data-poor nations becomes limited. This study investigates whether shared meteorological patterns between Caribbean countries can be leveraged to nowcast dengue activity in low-surveillance settings using climate-matched, well-surveilled nations as epidemiological proxies. Weekly and monthly dengue case data for six countries, the Dominican Republic, Jamaica, Puerto Rico, Trinidad and Tobago, Cuba, and Haiti, were extracted from the OpenDengue database for 2005–2024, and satellite-derived climate data were obtained from the NASA POWER API. Pairwise climate correlations revealed strong temperature synchrony across …

Indoor Environmental Quality Perceptions And Self-Reported Symptoms Among West Haven Va Healthcare Employees, Joseph Hyong Kim

Public Health Theses

Background: Indoor environmental quality in workplace settings influences worker well-being, yet the relationship between perceived workplace environment and reported symptoms remains less well characterized in heterogeneous healthcare settings. This study describes perceived workplace environmental quality and self-reported symptoms among employees at the West Haven Veterans Affairs (VA) Medical Center.

Methods: An observational, cross-sectional study was conducted of VA employees across clinical and non-clinical roles to assess perceived work environment, symptoms and indoor exposures using an electronic survey and personal and area air monitoring of indoor volatile organic compounds (VOCs) and viruses. Perceived workplace environmental quality was assessed using the MM-40 …

Pediatric Rheumatic Heart Disease Screening For Secondary Antibiotic Prophylaxis: An Explainable Shannon Energy Approach Using Heart Phonocardiogram In Northeast Brazil, Zhuohui Lin

Public Health Theses

Rheumatic Heart Disease (RHD), caused by Group A Streptococcus (GAS), remains a significant global health burden, particularly among children in low- and middle-income countries. Untreated GAS infection can lead to acute rheumatic fever and subsequent chronic valvular damage of RHD, such as mitral valve (MV) regurgitation. Hence, early detection is critical for the administration of Secondary Antibiotic Prophylaxis to prevent disease progression. Although deep learning models demonstrate high diagnostic accuracy, limited explainability restricts clinical adoption, especially in resource-limited settings. In this proof-of-concept study, we evaluated Shannon energy (SE) transformation as a proxy to differentiate holosystolic murmurs associated with RHD-related mitral …

Climate, Land Use, And Lyme Disease Risk In The United States, Mohan Li

Public Health Theses

Lyme disease is the most common vector-borne bacterial infection in the United States. It remains an important public health concern due to its high disease burden, expanding geographic distribution, and complex transmission cycle. Climate change is frequently regarded as a driver of Lyme disease emergence, as many previous studies suggested. However, ongoing debate about the magnitude and mechanisms of climate effects complicates the interpretation of this relationship. This review synthesizes evidence on how climate influences Lyme disease through both direct and indirect pathways, with a focus on studies relevant to the United States and North America.Climate directly affects Lyme disease …

Optimizing Positivity Cutpoints Using Validated Assessment Tools For Osteoporosis And Sarcopenia In Aging People Living With Hiv In Peru, Joselito Malca Hernandez

Public Health Theses

AbstractBackground: People living with HIV (PWH) are at increased risk of osteoporosis and sarcopenia, yet access to gold-standard diagnostic tools remains limited in many settings. Low-cost screening tools such as OST, SCORE, and SARC-F offer practical alternatives, but optimal cutpoints and their implications for clinical decision-making in PWH are not well defined.

Methods: We conducted a secondary analysis of cross-sectional data from 229 PWH aged ≥45 years receiving care in Lima, Peru. Osteoporosis was defined using DXA among postmenopausal women and men ≥50 years, and sarcopenia using AWGS-2019 and EWGSOP2 criteria. We evaluated the diagnostic performance of OST, SCORE, their …

Maternal Sleep, Sleep Medication Use, And Birth Outcomes: A Pilot Study Of The Pregnancy, Environment, And Child Health (Peach) Cohort, Samantha Lydell

Public Health Theses

Pregnancy is often a period of poor sleep quality. Previous research has linked reduced sleep quality and difficulty sleeping during pregnancy to adverse maternal and fetal outcomes. However, little is known about how sleep medication use may influence these associations. This pilot study examines the relationships between poor sleep, sleep medication use, and birth outcomes in the Pregnancy, Environment, and Child Health (PEACH) cohort. This study included 136 participants from the PEACH cohort linked to Yale New Haven Health delivery records. Poor sleep and sleep medication use were self-reported. Outcomes were gestational age at birth (days) and birth weight (grams). …

Successive Blood Meal Feeding And Wolbachia Impact On The Intra-Host Genetic Diversity Of Dengue Virus In Aedes Aegypti Mosquitoes, Braiya Nolan

Public Health Theses

Dengue virus (DENV) is a mosquito-borne RNA virus and increasing public health threat. Due to its error prone replication, single-nucleotide variants (iSNVs) are rapidly generated within the vector, leading to heterogeneity in viral populations, fitness, virulence, and transmissibility, including under vector control interventions. One such control strategy is the large-scale deployment of Wolbachia-infected mosquitoes worldwide. Wolbachia is an endosymbiotic bacterial biocontrol method that provides incomplete inhibition of DENV replication and transmission. Given its incomplete inhibition, it is critical to understand how Wolbachia impacts DENV-2 intra-host viral diversity. Additionally, successive blood meal feeding may influence intra-host viral diversity by supporting increased …

Characterization Of Tick Exoproteins Interacting With Anaplasma Phagocytophilum, Yilei Qin

Public Health Theses

Anaplasma phagocytophilum (Ap) is an Ixodes-transmitted obligate intracellular bacterium thatinfects neutrophils and causes human granulocytic anaplasmosis. Ap alternates between an infectious dense-cored (DC) form and a replicative reticulate cell (RC) form, and successful transmission depends on coordinated interactions at the vector–pathogen interface. Tick extracellular and secreted proteins (the tick exoproteome) likely contribute to Ap survival and transmission, yet many proposed tick factors remain computationally annotated with limited experimental validation. In this thesis, I prioritize candidate tick exoproteins, identified from yeast- display screens using whole Ap organisms, and evaluate them using a two-step validation strategy. First, I quantify tissue-specific expression of …

Protecting Older Individuals From Age Discrimination Harming Psychological Well-Being: Role Of Neighborhood Cohesion, Tongyu Qiu

Public Health Theses

Age discrimination is known to harm older adults’ mental health, yet factors that may protect against this harm have received little attention. Prior studies have focused primarily on individual-level factors rather than community-level characteristics, such as neighborhood cohesion, which may be more amenable to large-scale interventions and policies. To our knowledge, no prior study has examined whether neighborhood cohesion buffers the association between age discrimination and worse psychological well-being in older adults. Participants aged 60 years and older were drawn from the Midlife in the United States (MIDUS) study. We hypothesized that baseline age discrimination would predict worse psychological well-being …

Invasive Pneumococcal Disease: Outcomes And Vaccine Effectiveness By Risk Profiles Among A Pediatric Cohort From 2002 – 2025, Keyner Rojas

Public Health Theses

AbstractBackground: Invasive pneumococcal disease (IPD) remains a significant cause of morbidity and mortality among children globally, despite the widespread use of protein conjugate vaccines (PCVs). While the introduction and implementation of these vaccines have drastically reduced the incidence of vaccine-type invasive disease, shifts in circulating serotypes raise concerns of serotype replacement. Methods: This study is a retrospective observational study of pediatric IPD cases in Massachusetts from 2002 – 2025. Over the course of these 23 years, the Massachusetts Department of Public Health has operated an enhanced population-based, statewide surveillance system for IPD. Isolates of Streptococcus pneumoniae from normally sterile sites …