Digital Commons Network^™

Geospatial Analysis Of Violent Crime And Premature Mortality From Chd, Sarah Elise Conderino

Public Health Theses

Background: Cardiovascular disease (CVD) is the leading cause of death in the United States and many of these deaths are preventable. Studies have shown that neighborhood-level characteristics may contribute to health outcomes, but no study has yet examined whether neighborhood crime contributes to early mortality from CVD.

Objective: We examined geographic trends in the association between neighborhood crime rates and premature mortality from coronary heart disease (CHD) using New Haven, CT USA as a model city.

Methods: Neighborhoods in New Haven were established by existing census tracts. CHD deaths were identified from the Connecticut Master Death Files and violent crime …

Impact Of Gain-Of-Function Mutations In The Low-Density Lipoprotein Receptor Related Protein 5 (Lrp5) On Glucose And Lipid Homeostasis, Dinah Foer

Yale Medicine Thesis Digital Library

IMPACT OF GAIN-OF-FUNCTION MUTATIONS IN THE LOW DENSITY LIPOPROTEIN RECEPTOR RELATED PROTEIN 5 (LRP5) ON GLUCOSE AND LIPID HOMEOSTASIS. Dinah Foer, Meiling Zhu, Christine Simpson, Grace Lee, Rebecca Sullivan, and Karl L. Insogna. Section of Endocrinology, Department of Internal Medicine, Yale University, School of Medicine, New Haven, CT.

Investigations in animal models suggest a physiologic link between LRP5 and glucose and lipid homeostasis. However, the data in human studies is far from consensus. While LRP5 has been shown to be critical to Wnt signaling, the molecular mechanism for the effect on metabolism is unknown. We hypothesize that a high bone …

Modulation Of Immunity By The Immunologic Zipper: The Role Of Glucocorticoid-Induced Leucine Zipper In Extracoporeal Photochemotherapy, Hao Feng

Yale Medicine Thesis Digital Library

Extracorporeal photochemotherapy (ECP) is a cellular therapy that is FDA approved for the treatment of a variety of T cell mediated diseases, including cutaneous T cell lymphoma, graft-versus-host disease, and solid organ transplantation rejection. Its ability to selectively suppress and stimulate immunity while causing minimal to no side effects in patients distinguishes it from other therapies including pharmacologic agents. Despite the clinical success of ECP, the exact mechanism by which ECP generates immunotolerance and immunogenicity in patients has been elusive. Since monocytes interact with platelets and serum proteins in the ECP chamber to undergo differentiation into dendritic cells (DCs), we …

Longitudinal Characteristics Of Depression And Mood States Beginning In Primary Hiv Infection, Jessica Ashley Gold

Yale Medicine Thesis Digital Library

LONGITUDINAL CHARACTERIZATION OF DEPRESSION AND MOOD STATES BEGINNING IN PRIMARY HIV INFECTION. Jessica A. Gold, Marie Grill, Julia Peterson, Christopher Pilcher, Evelyn Lee, Frederick M. Hecht, Dietmar Fuchs, Constantin T. Yiannoutsos, Richard W. Price, Kevin Robertson, and Serena Spudich. Department of Neurology, Yale University, School of Medicine, New Haven, CT.

Though depression is known to frequently afflict those with chronic HIV, mood during the early course of HIV is not well characterized. In a prospective study we assessed mood during primary HIV infection (PHI, <1 year duration), its association with neuropsychological performance and markers of neurological disease, and its longitudinal course including effects of highly active antiretroviral therapy (HAART). The Beck Depression Inventory (BDI) and Profile of Mood States (POMS) subscales were longitudinally administered prior to and after HAART in PHI subjects. This evaluation of mood was done concurrently with blood, cerebrospinal fluid (CSF) and neuropsychological (total z and global deficit score, GDS) evaluation at each visit. Analysis employed Spearman's rho, logistic regression, and linear mixed models. 47.7% of the 65 men recruited at a median 3.5 months HIV duration met BDI criteria for clinical depression at baseline, classified as `mild' (n=11), `moderate' (n=11), or `severe' (n=9). Drug, alcohol, and depression history did not associate with BDI score. Proportional somatic-performance scores were worse than cognitive-affective scores (p=. 0045). Vigor subscore of POMS was reduced compared to norms and correlated with total z (r=0.33, p=0.013) and GDS (r=-0.32, p=0.016). BDI and POMS correlated with one another (r=0.85, p< .0001), but not with CSF or plasma HIV RNA, white blood cell (WBC) count, albumin ratio or neopterin. Improvement was not observed in BDI and POMS over 330 total follow-up visits, even after initiation of HAART. Depression was prevalent during PHI in our subjects, associated with abnormal somatic-performance and vigor scores. Neither neuropsychological performance nor disease biomarkers correlated with depressed mood. Mood indices did not improve over time in the presence of HAART.

Langerhans Cell Contributions To Ultraviolet Light-Induced Cutaneous Carcinogenesis, Marianna Freudzon

Yale Medicine Thesis Digital Library

Epidermal dendritic cells, called Langerhans cells (LC), were recently shown to facilitate DMBA/TPA-induced chemical carcinogenesis. LC contribution to UV-induced carcinogenesis, however, remains to be elucidated. We used the Langerin-DTA transgenic mouse model that lacks LC to characterize early and late effects of DNA damage in epidermis following exposure to UVB light. We found that LC density in LC-intact mice remains unchanged at 1hr and 24hr post 100 J/m2 UVB, suggesting that LC are poised to affect the surrounding epidermal cells following acute low-dose UVB exposure. During this time interval, LC-deficient mice had significantly fewer γH2Ax-positive cells within the epidermis, indicative …

Genomic Predictor Of Residual Risk Of Recurrence After Chemotherapy In High Risk Estrogen Receptor Positive Breast Cancers, Sabrina Khan

Yale Medicine Thesis Digital Library

Gene signature based prognostic tests can help improve adjuvant treatment decisions in early stage estrogen receptor positive (ER) breast cancers. Available tests in the clinic include Oncotype DX recurrence score (RS), PAM50 molecular class, and the Genomic Grade Index (GGI), which can identify high risk tumors that are likely to recur and have less favorable survival when treated with surgery and endocrine therapy alone. These high risk patients are recommended to also receive chemotherapy to improve their chance of survival. A subset of these "high risk" tumors is highly sensitive to adjuvant chemotherapy due to their high proliferation rates, and …

Predictors And Potential Mechanisms Of Improvement
 In Asthma Control In Children Following Adenotonsillectomy, Maria Koenigs

Yale Medicine Thesis Digital Library

Recent small observational studies suggest that asthmatic children receive clinical benefit in asthma control following adenotonsillectomy (TA), but little is known about which clinical and biological characteristics impact improvement. We enrolled 213 children undergoing TA, including 136 children with asthma and 78 controls, in a longitudinal observational cohort study (YCAAD). An asthma questionnaire, Asthma Control Test (ACT) scores, and serum asthma biomarkers levels were obtained at baseline and at six-months. Interim analysis compared patient characteristics to a historical cohort (CT-Kids) of 49 children with asthma who underwent TA. Urgent care visits (P < 0.001), oral steroid courses (P < 0.001), and ACT scores (P < 0.001) all improved in children with asthma following TA. Serum Th2 inflammatory markers, including IL-4 (P = 0.022) and IL-5 (P = 0.002), decreased following TA. Decreased IL-5 levels following surgery correlated with improvement in urgent care visits (P = 0.021), decreases in oral steroids (P = 0.02), and overall improvement in asthma control (P = 0.008). Children who were low or healthy weight, younger, female, had a history of sinusitis, and/or had a history of persistent asthma were more likely have improvement in their asthma following surgery. Elevations of serum IL-2, IL-4, IL-5, IL-13, IFN-γ, TNF-α, and GM-CSF levels were found in children whose asthma improved after TA. These clinical characteristics and biomarkers may help predict which children will receive maximum benefit in asthma control following TA.

Prevalence Of Tuberculosis Symptoms And Latent Tuberculosis Infection Among Prisoners In Northeastern Malaysia, Benjamin Margolis

Yale Medicine Thesis Digital Library

Background: Tuberculosis (TB) is a known public health threat to prison systems due to poor hygiene, crowded living conditions, poor health of inmates, and poor prison healthcare systems. The large population of HIV-infected people living in prisons is especially susceptible to increased TB transmission and higher mortality. In Northeastern Malaysia, there is no screening for active or latent TB infection (LTBI) in the prison system.

Aims and Hypothesis: This study serves to measure the prevalence and correlates of LTBI and active TB symptoms in HIV-infected and non-HIV-infected prisoners in Northeastern Malaysia. Given the host of factors that contribute to TB …

Characterization Of The Effect Of Braf Inhibitors On Melanoma Metabolism In Vitro And In Vivo, Alexander Marzuka

Yale Medicine Thesis Digital Library

Vemurafenib is the first FDA-approved personalized treatment for metastatic melanoma to show an improvement in survival. This serine threonine kinase inhibitor targets the mutated BRAF V600E protein, which occurs in approximately 50% of melanomas. The downstream effect of BRAF V600E blockade is inhibition of cell proliferation. Little is known about the effect of vemurafenib on glucose metabolism in melanoma cells. The Warburg effect, or the use aerobic glycolysis to generate energy and building blocks for cell proliferation, is a hallmark of cancer. Normal cells, in contrast, metabolize glucose through oxidative phosphorylation in the presence of oxygen and through glycolysis in …

A Novel Controlled Release Platform For In Situ Vascular Tissue Engineering, Joseph Thomas Patterson

Yale Medicine Thesis Digital Library

Autologous tissue engineered vascular grafts (TEVGs) are limited by graft stenosis. Small diameter TEVGs implanted as unseeded scaffolds are prone to failure by occlusive luminal proliferation of smooth muscle cells derived from endothelial precursors within a critical period of two weeks. The development, validation, and application novel platform for controlling TEVG performance by local delivery of peptide and/or small molecule therapeutic agents from the TEVG scaffold is presented with insights into the autologous TEVG biology and development.

We hypothesized that inhibition of TGF-βR1 by local delivery of SB-431542, a competitive inhibitor of ALK5/TGFβR1 signaling, is superior to systemic administration of …

Evaluation And Characterization Of The Biomechanical Properties Of Tissue Engineered Vascular Grafts Implanted In The Arterial Circulation, Brooks Van Udelsman

Yale Medicine Thesis Digital Library

We used a murine model to assess the in vivo evolving biomechanical properties of tissue engineered vascular grafts (TEVGs) implanted in the arterial circulation. The initial polymeric tubular scaffold was fabricated from (poly)lactic acid (PLA) and coated with a 50:50 copolymer of (poly)caprolactone and (poly)lactic acid (P[PC/LA]). Following seeding with syngeneic bone marrow derived mononuclear cells, the TEVGs (n=50) were implanted as aortic interposition grafts in wild-type mice and monitored serially using ultrasound. A custom biaxial mechanical testing device was used to quantify in vitro the circumferential and axial mechanical properties of grafts explanted at 3 or 7 months. At …

Identification Of Novel Anti-Brain Tumor-Initiating Cell Compounds Using High-Throughput Screening, Garth William Strohbehn

Yale Medicine Thesis Digital Library

Glioblastoma multiforme is the most common malignant primary intracranial tumor in adults. Despite years of advances in basic science knowledge about this disease including but not limited to cellular hierarchy, genetics, and mechanisms of proliferation and spread, overall survival of patients has remained unmoved for the past fifteen years, and long-term survivors are nearly nonexistent. Barriers to improved treatment occur in the realms of engineering and drug discovery: creation of an efficient delivery vehicle and identification of novel, efficacious small molecule compounds are necessary to achieve survival benefit in this disease.

In the following thesis, I describe efforts made by …

Group Based Trajectories Of Blood Pressure Components From Adulthood To Elderly In Chinese Workers, Ji Young Kwon

Public Health Theses

Objective: The study aimed to identify trajectories of systolic blood pressure (SBP),

diastolic blood pressure (DBP), and pulse pressure (PP) in Chinese adult workers from ages 18 to 81 years.

Methods: Analysis was conducted with a longitudinal data from Qingdao Port Health and Nutrition Examination Survey. This is a prospective study of employees of China's Qingdao Port Company that was initiated in 1999 and has been collecting annual measure of blood pressure. For our analysis, we focused on the cohort from 2000 to 2011. A group-based trajectory modeling was adopted to identify patterns of blood pressure over the lifespan. The …

Bulletin Of Yale University School Of Nursing 2014-2015, Yale School Of Nursing

Yale School of Nursing Bulletins and Catalogues

Series 110, Number 15

September 5, 2014

The Role Of Gene Regulation In Cancer: Studies Of Cancer-Related Phenotypes Mediated By Mex3d And By Microrna-618 Implicate Their Potential Oncogenic Role, Travis Whitfill

Public Health Theses

The control of gene expression is pivotal in the context of molecular pathogenesis of a number of diseases, and thus is of critical relevance to public health. An array of cellular tools exist in controlling gene expression, including epigenetic effects, non-coding RNAs, and RNA-binding proteins. These tools are critical to the modern study of public health, and are used in tandem with population-based studies. This work focuses on specific examples of non-coding RNAs and RNA-binding proteins, describing the effects of microRNA-618, a non-coding RNA, and MEX3D, a post-transcriptional regulator, in cancer.

MicroRNAs (miRNAs) form a class of highly conserved endogenous …

An Unhealthy Click: An Investigation Of Pro-Eating Disorder Website Visitation In A Community Sample, Andrea Alvarez Marin

Public Health Theses

Objective: This study compared pro-eating disorder website visitors and non-visitors on demographic characteristics, weight and diet related variables, eating disorder psychopathology, overvaluation of thinness and attitudes towards these sites. A new measure, the Thin Commandments Scale (TCS), was developed and preliminarily validated.

Methods: The study employed a community sample of 420 adults who completed a battery of questionnaires, which also included the Eating Disorder Examination Questionnaire (EDE-Q), the Sociocultural Attitudes Toward Appearance Questionnaire (SATAQ-3)-Internalization Subscale, and the Beck Depression Inventory (BDI). Additionally, participants responded questions regarding the harmfulness and acceptability of these sites, as well as regarding visitors' health.

Results: …

Evidence For Selection Acting On Immune-Related Iron Transport Genes In Wild Rodents, Dylan Adam Duchen

Public Health Theses

Every organism requires certain resources that they cannot endogenously produce; one such dietary component, iron, is essential for many basic cellular functions and the host-immune response. By studying patterns of genetic diversity within the genes involved in immune-related iron transport we can achieve a greater understanding of the evolutionary mechanisms which drive these processes, including those underlying host-pathogen interactions.

This thesis describes further evidence of patterns indicative of positive selection within apical regions of the transferrin receptor complex (Tfr1), sites known to be involved in an evolutionary arms race with pathogens, within two rodent species endemic to Europe and Asia, …

Variations In Semen Sample Parameters Among Men In A Fertility Clinic: Implications For Reproducibility In Epidemiologic Studies, Regina Esenam Edifor

Public Health Theses

BACKGROUND: In population studies, one semen sample is usually collected per individual but in clinical settings it is recommended that multiple semen samples are collected per individual for analysis. The goal of this study is to estimate the size of within-person variability in semen quality parameters with the ultimate goal of figuring out how many repeat samples are needed in a semen quality study to represent this. We will also investigate how accurately one can predict semen parameter values for an individual using the long-term average as a standard.

HYPOTHESIS: We hypothesize that a maximum of 2 semen samples has …

Designing Multi-Layered Nanoparticles For Combination Gene And Drug Cancer Therapy., Asiri Saumya Ediriwickrema

Yale Medicine Thesis Digital Library

Cancer continues to be a highly prevalent and lethal disease, despite significant advances in understanding tumor biology and developing new chemotherapies. Major obstacles in cancer chemotherapy are drug resistance and systemic toxicities. Potential strategies for addressing these problems include delivering combination therapies to overcome drug resistance, and utilizing synergistic agents to minimize dosing and subsequently drug toxicity. In turn, delivery can also be optimized to target the tumor site and consequently minimize systemic side effects. Polymer nanocarriers are gaining interest as vehicles for cancer therapeutics for their abilities to not only deliver multiple agents, but also target the tumor itself. …

Yale Medicine : Alumni Bulletin Of The School Of Medicine, Winter 2014, Yale University. School Of Medicine

Yale Medicine Magazine - alumni bulletin and magazine

This is the Winter 2014 issue of Yale Medicine: alumni bulletin of the School of Medicine, v. 48, no. 1. Prepared in cooperation with the alumni and development offices at the School of Medicine. Earlier volumes are called Yale School of Medicine alumni bulletins, dating from v.1 (1953) through v.13 (1965).

Antidepressants And Melanoma: Is There A Link?, Stephanie Douglas

Yale Medicine Thesis Digital Library

ANTIDEPRESSANTS AND MELANOMA: IS THERE A LINK? Stephanie R. Douglas, Deepak Narayan. Section of Plastic and Reconstructive Surgery, Department of Surgery, Yale University School of Medicine, New Haven, CT.

Cutaneous melanoma is the sixth most common cancer in the United States, and its incidence continues to rise steadily at a rate of 2-3% per year. Meanwhile nearly 11% of the general population is treated with antidepressant medication. Laboratory studies suggest a number of theoretical links between antidepressants and melanoma. Serotonin is a growth factor for melanocytes, and antidepressants upregulate components of the Wnt/beta-catenin, mTOR, and MAP kinase signaling pathways, all …

Eph-B4 Activation Reduces Neointimal Hyperplasia In Human Saphenous Vein, Daniel James Wong

Yale Medicine Thesis Digital Library

Despite the rise in percutaneous interventions, bypass surgery is an essential therapy for patients with advanced coronary and peripheral artery disease. Nearly half of the saphenous vein grafts used in these operations are eventually complicated by pathologic remodeling known as neointimal hyperplasia (NIH). Recent work in animal models has shown that the development of NIH can be reduced by stimulation of the receptor tryrosine kinase Eph-B4 by systemic injections of its ligand ephrin-b2. The purpose of this study was to determine whether the reduction of intimal hyperplasia observed with Eph-B4 stimulation in animal models translated into human tissues. Specifically we …

Thermohaline Staircases In The Western Mediterranean Sea, Harry L. Bryden, Katrin Schroeder, Stefania Sparnocchia, Mireno Borghini, Anna Vetrano

Journal of Marine Research

Thermohaline staircase structures are commonly observed in the western Mediterranean Sea within the halocline-thermocline connecting the Levantine Intermediate Water at about 400 m depth with the western Mediterranean deep waters below 1,500 m. In this halocline-thermocline where warmer, saltier waters overlie colder, fresher deep waters, salt finger mixing processes are thought to be active and produce staircases with layers of order 75 m thickness containing nearly constant properties separated by sharp steps of order 6 m thickness with jumps in properties between the layers. While the layers have nearly constant salinity, potential temperature, and potential density, each property decreases very …

A Constraint On The Thickness-Weighted Average Equation Of Motion Deduced From Energetics, Kunihiro Aoki

Journal of Marine Research

This study reviews the system governed by the thickness-weighted average (TWA) equation of motion, considering energetics. It is known that the TWA equation of motion based on the primitive equation describes the fluid motion with the residual mean velocity defined as the TWA velocity and is written in the same form as the nondissipative primitive equation, except that the eddy momentum fluxes (the interfacial form stress and Reynolds flux associated with eddy motion) are embedded in this equation. Also, incompressibility and density (buoyancy) conservation in the adiabatic condition hold in this system. In this study, considering that the TWA system …

On The Structure And Distribution Of Thin Anticyclonic Lenses In The Southeast Pacific Ocean, T. Rossby

Journal of Marine Research

The velocity structure of an anticyclonic lens in the southeast Pacific centered at 300–400 m depth was scanned in detail with a 75 kHz acoustic Doppler current profiler on the RV Atlantis during a February 2010 transit along 20° S. Embedded in the main thermocline with a vertical span of ∼500 m, the lens had an overall diameter of ∼150 km with a peak speed of 0.33 m s^–1 at ∼35 km radius. Knowledge of the velocity field permitted determination of energetics and vorticity properties in detail. The ratio of potential to kinetic energy was ∼14, and the relative …

Medicine@Yale July/August 2014 Volume 10, Issue 2, Yale School Of Medicine Office Of Communications

Medicine@Yale - development newsletter

Medicine@Yale : advancing biomedical science, education and health care was a print and online newsletter which published news about academics, research and philanthropy for alumni, donors, faculty, students and the general public. It was initially published 6 times a year and then changed to a quarterly schedule. The first issue came out June/Jul. 2005. The final issue was published in May/June 2022, vol. 17, issue 1. Published by Yale School of Medicine, Office of Communications.

Novel Interdisciplinary Approaches To Understanding Kidney Transplantation Outcomes, Neel Butala

Yale Medicine Thesis Digital Library

This thesis details 2 studies using novel approaches to understand kidney transplant outcomes: instrumental variables and social network analysis. Together, these studies demonstrate the value of interdisciplinary approaches to advance the field of kidney transplantation.

While some studies have found an association between delayed graft function (DGF) after kidney transplantation and worse long-term outcomes, a causal relationship remains controversial. In our first study, we investigate this relationship using an instrumental variables model (IVM), a quasi-randomization technique for drawing causal inferences. We identified 73,714 adult, deceased-donor, kidney-only transplant recipients from the Scientific Registry of Transplant Recipients (SRTR) between 1997 and 2010. …

Playforward: Elm City Stories Interactive Group-Based Curriculum: An Intervention On Hiv Risk Behaviors In Urban Racial And Ethnic Minority Youth, Anna North

Public Health Theses

There is a growing epidemic of HIV in young, racial and ethnic minority populations (Centers for Disease Control and Prevention, 2008). PlayForward: Elm City Stories is an evidence-based, theory-driven videogame intervention developed by the Yale School of Medicine research group, play2PREVENT to impact HIV risk behaviors in urban racial and ethnic minority youth, ages 11-14 (play2PREVENT). The PlayForward: Elm City Stories intervention manual seeks to build on the videogame by adding an in-person group dimension to the individualized intervention. The manual provides a group-based interactive, in-person curriculum addressing decision-making and risk behaviors for HIV exposure among 11-14 year olds, and …

Household Food Insecurity And Obesity Risk In An Urban Slum In Brazil, Krysta Peterson

Public Health Theses

Background: The prevalence of obesity is growing among the poor. Household food insecurity (HFI) may partly explain this trend as individuals experiencing it may cope by consuming low-cost high calorie meals with little nutritive value. This study aimed to estimate the prevalence of HFI, identify its risk factors, and assess the relationship with obesity among adults in an urban slum community in Salvador, Brazil.

Design: This cross-sectional study interviewed participants at home to assess socioeconomic status, demographics, HFI (measured by the Brazilian Food Insecurity Scale (EBIA)), and health. Anthropometric measurements (height, weight, waist circumference) of each respondent were taken to …

Soil-Transmitted Nematode Infections Among School-Age Children In Rakai District, Uganda, Jensen Dalton Reckhow

Public Health Theses

One billion people are currently infected with at least one soil-transmitted nematode (STN), and over 161,600 school-aged children in sub-Saharan Africa live in areas where the prevalence exceeds 20%. STN infections cause malnutrition and cognitive deficits that limit productivity and may contribute to endemic poverty. Despite this significant and recognized disease burden, research on these diseases remains piecemeal; the majority of scientific understanding of these conditions is derived from a handful of small studies. Data regarding prevalence, intensity, and effectiveness of treatment of STN infections in Rakai District, Uganda is particularly limited, and the Ministry of Health has discontinued surveillance …