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Evaluating Nebulizer Efficiency For Phage Therapy In Drug-Resistant Pseudomonas Infections, Daniel Thompson

Yale Medicine Thesis Digital Library

Background

The global rise of multidrug-resistant (MDR) Pseudomonas aeruginosa necessitates novel therapeutic approaches, particularly for patients with cystic fibrosis (CF). Bacteriophage therapy, delivered via inhalation, offers a targeted and potentially transformative treatment for pulmonary infections caused by MDR pathogens. This study aimed to evaluate the effects of nebulizer type and bacteriophage morphology on viable phage recovery and aerosol particle size distribution, hypothesizing that nebulizer-phage compatibility significantly influences the delivery of viable phages to the lower respiratory tract.

Methods

We conducted an in vitro study utilizing two clinically relevant nebulizer systems: the Pari LC Plus jet nebulizer and the Altera eFlow …

Personalized Therapeutic Approaches For Cutaneous T-Cell Lymphoma (Ctcl), Madisen Swallow

Yale Medicine Thesis Digital Library

Cutaneous T-cell lymphoma (CTCL) is a non-Hodgkin lymphoma characterized as a malignancy of T-cells that variably involves the skin, lymph nodes, and blood. Many therapeutic options exist for patients with CTCL, ranging from narrow-band UVB, extracorporeal photopheresis, total skin electron beam therapy, retinoids, histone deacetylase inhibitors, antibody drug conjugates, and chimeric antigen receptor (CAR) T-cell therapy. Despite the various advances in treatment options, these therapies are non-curative with overall response rates ranging from 30 to 55%, warranting the need for better alternatives that also aim to reduce toxic systemic effects. Project 1: Prior work in a series of publications by …

Confessions Of A Failed Revolutionary Subject: Toi Derricotte And The Black Notebooks In The Archive, Kavya Jain

Kaplan Senior Essay Prize for Use of Library Special Collections

In this essay, I use black feminist methodologies to theorize archival voice as opposed to silence, drawing from Toi Derricotte’s 1997 book The Black Notebooks: An Interior Journey and its drafts. I examine Derricotte’s published and unpublished writings on the psychological wounds of racism, internalized antiblackness, shame, and the racial and relational politics of being white-presenting to understand her vision of how we free ourselves from the toxic imaginaries of race. I focus on Derricotte’s use of confession and her commitment to wayward speech, or saying the unsayable, to challenge political ideology’s domination of language and harness the political possibility …

Contraceptive Counseling For Transgender & Gender Diverse Patients: Provider Knowledge & Experience, Kathryn Callahan

Yale Medicine Thesis Digital Library

Many transgender and gender diverse (TGD) individuals have contraceptive needs. Contraceptive counseling in this population is often nuanced due to the diverse experiences and healthcare goals of TGD individuals. Testosterone therapy is an important component of gender affirming care for some transgender and gender diverse (TGD) individuals. A common misconception among patients and providers is the role of testosterone in pregnancy prevention. Testosterone is not an effective form of contraception due to its inconsistent suppression of ovulation. Previous studies have shown that some patients who use testosterone for contraception do so based on guidance from their healthcare provider. Therefore, this …

Atrial Myocyte Ampk Deletion Alters Single Nuclear Profiles In Mice, Julia Nicole Eisen

Yale Medicine Thesis Digital Library

Atrial fibrillation (AF) is the most common arrhythmia worldwide with about 1 in 4 adults expected to develop the condition in their lifetime. AMP-activated kinase (AMPK) is a critical energy sensor and regulates tissue energy and substrate metabolism. Our lab has previously shown that atrial cardiomyocyte-specific cardiac AMPK deletion induces electrophysiologic changes, left atria structural remodeling and spontaneous AF. The mechanism by which loss of AMPK and consequent metabolic stress leads to AF has not yet been elucidated. Using single nuclear RNA sequencing (snRNA sequencing) of mouse heart atria from mice with atrial cardiomyocyte AMPK deletion, we begin to investigate …

Mass Sars-Cov-2 In A State Correctional System During The Pandemic, Charlotte Kim

Yale Medicine Thesis Digital Library

Mass screening has been shown to be more efficient in identifying infections in correctional facilities compared to symptom-based screening, but little is known about the impact of systematic mass screening on timely isolation of infectious cases over the course of the entire pandemic. Between March 2020 and May 2023, the Connecticut Department of Correction (CT DOC) performed a multifaceted SARS-CoV-2 testing strategy for its incarcerated population, which included RT-PCR for mass screening, as well as rapid antigen testing for contact tracing, symptom-based screening, and other miscellaneous reasons. Testing data reveals that mass screening identified 48% of all positive results, whereas …

Pregnancy Outcomes After Glp-1 Receptor Agonist Exposure And Ethical Considerations, Nishita Pondugula

Yale Medicine Thesis Digital Library

The objective of this study is 1) to understand the effect of GLP-1 receptor agonist (GLP-1RA) use in the year prior to conception on risk of developing hypertensive disorders of pregnancy (HDP) and on gestational weight gain (GWG), and 2) to analyze important ethical considerations relevant to research in pregnancy and specifically related to GLP-1RAs.All patients delivering between 2014-2024 with evidence of GLP-1RA exposure in the year prior to conception were identified through electronic medical record (EMR) query with hand review to confirm exposure. GLP-1RA exposed patients were classified according to GLP-1RA indication for use: 1) pregestational diabetes mellitus (PGDM) …

Macrophage Migration Inhibitory Factor And D-Dopachrome Tautomerase As Biomarkers And Key Modulators Of Tumor Progression In Head And Neck Cancer And Melanoma, Caroline Naomi Valdez

Yale Medicine Thesis Digital Library

Macrophage Migration Inhibitory Factor (MIF) and its homolog D-dopachrome Tautomerase (DDT) are pro-inflammatory cytokines implicated in tumor progression across multiple cancers. Both MIF and DDT act through canonical CD74 and non-canonical CXCR2/4/7 signaling pathways, which contribute to immune suppression and tumor progression. Elevated MIF levels are associated with metastasis and poor prognosis in HNC and contribute to immune checkpoint inhibitor (ICI) resistance in melanoma. DDT’s role in cancer is not well understood. This study aims to evaluate the expression and therapeutic potential of MIF and DDT inhibition, focusing on their ability to modulate immune responses and improve survival outcomes as …

Bringing Culinary Medicine Teaching Principles To Children In The New Haven Community: An Interventional Pilot Study, Rachel Lutz

Yale Medicine Thesis Digital Library

Culinary medicine is a growing field dedicated to combining culinary skills and evidenced-based practices to promote health. While it has proven to be efficacious in improving biometrics for chronic diseases in adults, potential remains for its application in pediatric populations. This pilot study creates and evaluates a one-time community-based culinary medicine intervention for a mixed-age pediatric group. The intervention included a didactic lecture and five interactive stations for 20 research participants and 22 non-research participants at a community site. The intervention was evaluated for knowledge, attitudinal, and behavioral impact using pre-post surveys. Given the importance of food access in the …

Chimerism Testing In Myeloid Malignancies: Practical Guidance And Clinical Correlates, Christian Puzo

Yale Medicine Thesis Digital Library

Relapse is the primary cause of mortality for patients with myeloid malignancies post-allogeneic stem cell transplant (aSCT). As early intervention for those deemed high risk for relapse may improve outcomes, identification of residual malignant cell burden is of critical importance. Chimerism testing, the use of DNA sequencing technology to determine the relative percentage of donor to recipient hematopoietic cells post-aSCT, offers a practical metric to monitor for residual leukemic cell burden. The precise value of donor chimerism is influenced by many procedural and contextual factors, and multiple strategies, including the analysis of specific hematopoietic cell subsets, termed lineage-specific chimerism (LSC), …

Development And Application Of New Method And Platform For Correlated Oxides, Zheting Jin

Yale Graduate School of Arts and Sciences Dissertations

Strongly correlated oxides, including high-temperature superconductors such as cuprates and nickelates, exhibit complex quantum phenomena that can challenge conventional electronic structure theories. This thesis develops and applies advanced computational methods to study these systems, aiming to provide a comprehensive first-principles description of their structural, spin, and electronic properties. First, a novel cluster slave-particle method is introduced to improve the treatment of electron correlations in extended Hubbard models, capturing strong correlation effects with high computational efficiency and benchmarking well against established many-body techniques. This method is then combined with density functional theory calculations and applied to cuprates, where we demonstrate how …

The Influences Of Redox-Active Ligands On Nitrogen Reduction Catalysts, Alexander S. Hegg

Yale Graduate School of Arts and Sciences Dissertations

This thesis describes the synthesis, characterization, and reactivity towards N2 reduction of a number of group 6 and 7 transition metal complexes bearing redox-active ligands. Chapter 1 introduces the field of nitrogen fixation, the role of transition metal catalysts in mediating nitrogen reduction, and some of the challenges that potential catalysts must overcome. Chapter 2 describes a number of molybdenum porphyrin complexes that were viable catalysts for N2 reduction with samarium diiodide and alcohol. The reduction of the ligand facilitates chemical transformations at the metal with strong acids and leads to NH3 formation. Chapter 3 describes the effects of exchanging …

The Shaping Of Religion Through Empire In Modern Korea, 1876-1948, John Grisafi

Yale Graduate School of Arts and Sciences Dissertations

This dissertation covers the roles of multiple empires in the discursive formation of religion in modern Korea, with emphasis on the period from 1876 through 1948. I argue that although semi-analogous terms and ideas to “religion” existed in Korea prior, the coinage of the modern Korena term for religion, chonggyo (종교, 宗敎) in 1883 and its subsequent discursive development were heavily shaped by imperialism, colonialism, and modern globalization. The pressures and influences of empires triggered a coalescence of Korean concepts of religion and related ideas. But the involvement of multiple empires as well as Korean interests, and the beliefs and …

Structural Studies Of Cellular Prion Protein And Amyloid-B Oligomers, Lauren Klein

Yale Graduate School of Arts and Sciences Dissertations

Alzheimer's Disease (AD) is a neurodegenerative disease with significant societal impacts. AD is the only top ten leading cause of death that cannot be prevented, cured, slowed, or even diagnosed before symptoms are present. AD, similar to other neurodegenerative diseases, has been linked to protein aggregation as the key factor in the disease pathology. However, the mechanism by which AD proliferates is poorly understood. Recent advancements in techniques and methods in structural biology, including nuclear magnetic resonance (NMR) and electron microscopy (EM), have opened a new era of studies into protein aggregates implicated in neurodegenerative diseases, including AD. Therefore, this …

Gene Expression Regulation By Pabpn1 Phosphorylation And Microexon Splicing, Jackson Miles Gordon

Yale Graduate School of Arts and Sciences Dissertations

The processing of pre-mRNAs into mature mRNAs is a key regulatory step in eukaryotic gene expression programs. Before an mRNA can be exported to the cytoplasm, its 5′ end must be modified with a 7-methylguanosine cap structure, intervening non-coding sequence must be removed (spliced), and a poly(A) tail must be synthesized at its 3′ end. Each of these processes are dynamic and provide contextual regulation, tuning an mRNAs coding capacity, stability, and translation potential as needed. The Neugebauer Lab has developed highly specialized tools to dissect how RNAs are spliced, cleaved, and polyadenylated in numerous biological systems. In this study, …

Long Covid And Vulnerability To Climate Change’S Health Effects: An Informational Booklet For Healthcare Settings, Rachel Nussbaum

Public Health Theses

According to the World Health Organization, around 10–20% of people infected by COVID-19 may go on to develop symptoms that can be diagnosed as Long COVID, also known as the post-acute sequelae of COVID-19 (PASC). While the risk of Long Covid among people who received the primary vaccine series fell to 3.5% in one study, as of September 2024, over 1.3 million Americans were being infected with SARS-CoV-2 every day, and reinfections increase the likelihood of experiencing Long Covid in some studies. Continued transmission of SARS-CoV-2 has led to roughly 400 million people experiencing infection-associated chronic conditions, creating an accumulating …

The Role Of Climate Change In The Pandemic Agreement Negotiations, Cristina Arnes Sanz

Public Health Theses

Introduction: For over three years, Member States of the World Health Organization (WHO) have been negotiating a treaty to prevent, prepare for, and respond to future pandemics. The Pandemic Agreement is anticipated to be adopted at the World Health Assembly in May 2025. Growing scientific evidence underscores the effects of climate change on infectious diseases, including those that could lead to pandemics. This thesis examines how climate change has been addressed in the drafting and negotiations of the Pandemic Agreement.

Methods: All the references related to climate change in the transcripts of the publicly broadcast Intergovernmental Negotiating Body (INB) meetings …

Innovative Approaches To Combat Triple-Negative Breast Cancer: Integrating Metabolic Modulation, Advanced Therapies, And Lifestyle Interventions, Ngozi Damilola Chidumebi Akingbesote

Yale Graduate School of Arts and Sciences Dissertations

Triple-negative breast cancer (TNBC), an aggressive and often lethal subtype of breast cancer, continues to challenge researchers and clinicians due to its poor prognosis and limited therapeutic options. This thesis explores novel therapeutic strategies that integrate metabolic modulation, advanced radionuclide therapies, and lifestyle interventions to combat TNBC effectively. The first component investigates metabolic scaling and its implications for cancer metabolism. Gene and protein expression analyses across species reveal that metabolic processes, including oxidative metabolism and detoxification, scale inversely with body mass. This foundational insight underscores the importance of systemic metabolic regulation in understanding cancer progression. In the realm of cancer …

Mental Representations Of Computational Processes, Marlene Berke

Yale Graduate School of Arts and Sciences Dissertations

Human intelligence is uniquely powerful and flexible - operating in an enormous range ofsituations, from those as everyday as driving in traffic while carrying on a conversation, to those as extraordinary as cooperating to shift a culture. Work in cognitive science over the past decades has argued that two foundational types of representations form the building blocks of human intelligence: representations of the physical world in terms of objects, forces, spaces, substances, and so on (Carey, 2009), and representations of the social world in terms of agents and their mental states, like goals, beliefs, and knowledge (Gopnik, Meltzoff, & Bryant, …

Essays In Macroeconomics And Finance, Francesco Beraldi

Yale Graduate School of Arts and Sciences Dissertations

This dissertation consists of three independent essays in which I study how financial markets affect macroeconomic outcomes. I combine rich micro-data and structural models with heterogeneity to shed light on how interactions among different agents influence business cycle fluctuations and the distribution of resources in the economy. I leverage this approach to address central questions covering financial intermediation, household and corporate finance, and their implications for macroeconomic policy and financial stability. Chapter 1: Banking Relationship and Loan Pricing Disconnect. In the first chapter, I study how long-term relationships between banks and firms shape loan pricing and capital allocation. I use …

Essays On Consumer Inferences, Mohin Banker

Yale Graduate School of Arts and Sciences Dissertations

Consumers infer from what they know to impute what they wish to know. For example, to estimate the quality of a new product, one may infer that a product's price reflects its quality. This dissertation is composed of three essays investigating factors that affect consumers' inferences. The first essay examines how inferences of positive information differ from inferences of negative information, and shows that positive information is generalized to new objects more than negative information, all else equal. For instance, a good restaurant affects judgments of similar restaurants more than a bad restaurant does. The second essay investigates inferences about …

When Do Children Think Inequality Is Fair?, Pinar Aldan

Yale Graduate School of Arts and Sciences Dissertations

Psychological research suggests that from infancy, humans are highly attuned to fairness and expect resources to be fairly allocated. However, despite this early sensitivity, people ultimately learn to live with - and sometimes even justify - widespread societal inequalities. This thesis explores how children, who in principle deeply value fairness, come to tolerate economic disparities. Through four chapters, this thesis examines how individuals of different ages interpret reasons for inequality that are common in social life yet underexplored in developmental research. Chapter 2 investigates how people reason about unequal compensation in division-of-labor contexts, where individuals assume distinct, qualitatively different roles. …

Microwave Techniques For Neutrino Mass Measurement, Arina Bykadorova Telles

Yale Graduate School of Arts and Sciences Dissertations

Direct neutrino mass measurement is one of the frontiers of particle and nuclear physics, with the most recent measurements setting an upper bound of 0.45 eV/c^2 and cosmological models and observations predicting an upper bound on the sum of neutrino masses of 0.12 eV/c^2. The next generation of neutrino mass experiments require new technology to push beyond the statistical and systematic limits of current measuring capabilities. Project 8 is a collaboration seeking to make this possible by combining the well-established tritium endpoint method with a relatively new technique called CRES. CRES uses the RF emission of electrons undergoing cyclotron motion …

Investigating Non-Canonical Roles Of Atr And Chk1 Throughout The Cell Cycle, Yoon Ki Joo

Yale Graduate School of Arts and Sciences Dissertations

Chromosome Instability (CIN), which results from DNA damage in interphase and chromosome missegregation in mitosis, is considered to be a potent driver of cancer. To prevent CIN, cells harbor the DNA Damage Response (DDR) pathway, which is responsible for detecting and repairing damaged DNA. Because of their importance in preventing CIN, the core members of the DDR pathway such as Ataxia Telangiectasia and Rad3-related (ATR) and Checkpoint kinase 1 (CHK1) have been studied as promising targets in cancer therapy. However, clinical trials show that ATR and CHK1 inhibitors elicit adverse side effects with unknown reasons. Recent research suggests that one …

Resolving The Three-Dimensional Interactome Of Human Accelerated Regions During Human And Chimpanzee Neurodevelopment, Atreyo Pal

Yale Graduate School of Arts and Sciences Dissertations

Human Accelerated Regions (HARs) are regulatory elements highly conserved across species but exhibit a significant excess of human-specific sequence changes. They include transcriptional enhancers with human-specific activity and have been implicated in the evolution of the human brain. However, our understanding of how HARs contributed to uniquely human features of the brain is hindered by a lack of insight into the genes and pathways that HARs regulate. It is unclear whether HARs acted by altering the expression of gene targets conserved between HARs and their chimpanzee orthologs or by gaining new gene targets in human, a mechanism termed enhancer hijacking. …

Continization And Language Representation Of Chemical Information, Haote Li

Yale Graduate School of Arts and Sciences Dissertations

Throughout human history, our ancestors have continuously expanded the frontiers of their interests in nature. Chemistry is one of the essences of such explorations. Yet, despite countless discoveries and experiments, we are still on a journey to examine the possibilities within our finite time. With an ever-growing amount of information and open access to public resources, we are experiencing an inflection point. This moment redefines how efficiently we can solve problems, and the key lies in integrating increasing insights from the entire history of knowledge. Algorithms, in contrast to human efforts, are scalable with the amount of available hardware. In …

Methodological Innovations In Causal Inference: Estimation, Testing, And Decision Making, Yitan Wang

Yale Graduate School of Arts and Sciences Dissertations

Causal inference has been an important topic across many fields, such as computer science, statistics, econometrics, epidemiology, psychometrics, and political science, for decades. In this dissertation, we present methodological innovations in causal inference for three problems: estimation, testing, and decision making. In the first chapter, we provide an overview of this dissertation and introduce potential outcomes framework and confounded contextual bandit. In the second chapter, we describe a new design-based framework for drawing causal inference in randomized experiments. Causal effects in the framework are defined as linear functionals evaluated at potential outcome functions. Knowledge and assumptions about the potential outcome …

New Statistical Methods For Mediation Analysis With Independent And Correlated Data, Chao Cheng

Yale Graduate School of Arts and Sciences Dissertations

Causal mediation analysis is a popular statistical tool for evaluating the extent to which an observed exposure-outcome relationship is mediated by an intermediate variable, also referred to as the mediator. Through mediation analysis, the total effect (TE) from the exposure on the outcome can be decomposed into a natural indirect effect (NIE) through the mediator and a natural direct effect (NDE) whose impact is due solely to the exposure and possibly other mediators. Causal mediation analysis has been applied in a variety of empirical research fields, including but not limited to epidemiology, implementation science, economics, and psychology. In implementation science, …

Real-Time Synthesis And Characterization In Quantum Materials: Insights From Superconducting Nickelate Research, Wenzheng Wei

Yale Graduate School of Arts and Sciences Dissertations

This dissertation reports on developments in quantum materials synthesis and characterization, with an emphasis on the study of superconducting nickelates through molecular beam epitaxy (MBE) and real-time synchrotron hard X-ray data analysis. The work elaborates on the developments in MBE synthesis, real-time characterization, and strategic materials design, and leads to the discovery of a nickelate superconductor. High resolution X-ray diffraction measurements were taken at the Advanced Photon Source, Argonne National Laboratory.The dissertation reports on the development of real-time analysis frameworks for both synthesis and characterization. This includes dynamic MBE source flux calibration techniques using RHEED and the shutter-control method, as …

Digital Identity Infrastructure, Jonathan Evan Hochman

Yale Graduate School of Arts and Sciences Dissertations

This dissertation proposes a uniform infrastructure for identifying users and data on the Internet. It identifies the questions we need to ask, provides terminology to think and speak about digital identity, introduces new cryptographic primitives to support digital identity services, and finally presents a sequence of applications that could be built upon the foundation of a shared digital identity infrastructure. These solution sketches are not meant as final specifications. They are examples to demonstrate how digital identity infrastructure could make it easier for digital platforms to deploy new services, improve privacy, reduce user frustration, and support the rule of law …