Digital Commons Network^™

The Heterotaxy Candidate Gene, Tmem195, Regulates Nuclear Localization Of Beta-Catenin, Anna Ruth Duncan

Yale Medicine Thesis Digital Library

Congenital heart disease (CHD) affects 1 in every 130 newborns and is the leading cause of infant mortality (2). Heterotaxy (Htx), a disorder of left-right (LR) development, commonly leads to CHD. Despite aggressive surgical management, patients with Htx have poor survival rates and severe morbidity due to their complex CHD. Many of the genetic causes of Htx remain undefined, however, a recent genetic analysis of Htx patients identified a single mutant allele in the novel candidate gene, TMEM195 (3). TMEM195 is an alkylglyercol monooxygenase that cleaves ether lipids, but neither its molecular target nor its role in development has been …

Limitations Of Administrative Databases In Orthopaedic Surgery Research: A Study In Obesity And Anemia, Nicholas Golinvaux

Yale Medicine Thesis Digital Library

The use of national inpatient databases for orthopaedic surgery research has been increasing. However, large databases that rely on administrative data, such as International Classification of Diseases Ninth Revision (ICD-9) codes, may misrepresent patient information, thus affecting the results of studies using this data.

The present study uses easily quantified and objective variables of obesity and anemia as example comorbidities to assess the accuracy of ICD-9 codes in the setting of their continued use in orthopaedic surgery database studies.

For each study arm, a large inpatient population was obtained from the Yale-New Haven hospital. Each patient's medical record was reviewed, …

Complications And Length Of Stay Following Spine Surgery: Analyzing Local And National Cohorts, Jordan Alexander Gruskay

Yale Medicine Thesis Digital Library

Complications following spine surgery are widely reported but poorly characterized. The effect of preoperative comorbidities and postoperative complications on length of stay (LOS) has not been evaluated. It would be ideal to have a clearer understanding of the variables affecting LOS to facilitate setting expectations and control costs. Using complications and LOS as outcomes, we can also characterize the risks inherent with surgical practices, such as the use of iliac crest bone graph (ICBG) in spinal fusion.

The study consisted of three aspects. First, the effect of pre and perioperative variables on LOS for 103 patients undergoing posterior lumbar fusion …

Tartrate-Resistant Acid Phosphatase: Prognosis In Colorectal Cancer And The M1/M2 Distinction., Chi-Joan How

Yale Medicine Thesis Digital Library

Recent research has indicated that separate populations of macrophages are

associated with differing outcomes in cancer survival. In our study, we examine

macrophage expression of tartrate resistant acid phosphatase (TRAP) and its effect on

survival in colon cancer. Immunohistochemical analysis on colorectal adenocarcinomas

confirmed macrophage expression of TRAP. Co-localization of TRAP with CD68, a pan

macrophage marker, revealed that TRAP is present in some but not all subpopulations of

macrophages. Further co-localization of TRAP with CD163, an M2 marker, revealed that

TRAP is expressed by both M2 and non-M2 macrophages. TRAP expression was then

measured using the AQUA method of …

Novel Mechanisms Of Trophoblast Responses To Antiphospholipid Antibodies And Therapeutics In Obstetric Antiphospholipid Syndrome, Stefan Mathias Gysler

Yale Medicine Thesis Digital Library

Obstetric antiphospholipid syndrome (APS) is a systemic autoimmune disorder characterized by circulating antiphospholipid antibodies (aPL) and an increased risk of recurrent pregnancy loss and preeclampsia. Current treatments, such as low molecular weight heparin (LMWH) may maintain pregnancy but do not reduce the risk of these late gestational complications. aPL trigger placental inflammation by activating trophoblast Toll-like receptor 4 (TLR4), leading to cytokine production. Since some microRNAs (miRs) regulate TLR responses, this study sought to determine the functional role of aPL-induced miR expression in regulating trophoblast inflammation. Since vitamin D deficiency is common in APS patients, the effect of vitamin D …

Neuropsychological Testing Impairment In Acute Hiv And The Effects Of Immediate Antiretroviral Therapy, Idil Kore

Yale Medicine Thesis Digital Library

Acute HIV infection (AHI) is accompanied by central nervous system infection and immune activation. We investigated baseline predictors of neuropsychological (NP) performance in Thai participants with AHI and the effect of antiretroviral therapy (ART) on domains of functioning known to be affected by HIV.

36 participants with AHI (89% male, median age of 28 years, median time since HIV exposure of 19 days) were evaluated at baseline and 3 and 6 months after ART. Performance on the Grooved Pegboard test (GP), Color Trails 1 & 2 (CT1, CT2), and Trails Making Test A (TM) were standardized to 251 age and …

Cost Analysis Of Percutaneous Pulmonary Valve Implantation Versus Surgical Pulmonary Valve Replacement, Xin He

Yale Medicine Thesis Digital Library

Right ventricular outflow tract (RVOT) and pulmonary valve dysfunction account for roughly 20% of all congenital heart diseases. Over time, these types of dysfunction can lead to right heart failure, which is associated with significant morbidity and mortality. Improvements in RVOT and pulmonary valve function may reverse some of the deleterious effects. Historically, surgical pulmonary valve replacement has been the mainstay method of pulmonary valve repair. In 2010, percutaneous pulmonary valve implantation (PPVI) was introduced in the US. This study analyzed the healthcare costs for 47 and 51 patients that underwent PPVI and surgical pulmonary repair, respectively, at Yale-New Haven …

Blood-Pressure Reduction Is Associated With Worsening In Renal Function But Does Not Prevent Successful Decongestion In Patients Treated For Acute Decompensated Heart Failure, Alexander Kula

Yale Medicine Thesis Digital Library

Background: Reductions in blood pressure are common during the treatment of acute decompensated heart failure (ADHF) and strongly associated with worsening renal function (WRF). However, it is unclear whether a decline in systolic blood pressure (SBP), and the associated deterioration in renal function, might limit successful diuresis.

Methods: We analyzed consecutive admissions with a primary discharge diagnosis of ADHF (n=657). Metrics of diuresis were assessed for their association with a decline in SBP from admission to discharge in addition to the use or titration of guideline recommended heart failure therapies (GDMT). SBP-reduction was defined as a relative reduction in SBP …

Age-Related Intravenous Induction Dosing In Patients Undergoing Gastrointestinal Surgeries, Jia Liu

Yale Medicine Thesis Digital Library

Background:

It has been shown that elderly patients have decreased anesthetic requirements due to age-related changes in pharmacokinetics, pharmacodynamics and drug sensitivity. Previous work has also shown that anesthetic dosing is often not being rigorously corrected for age.

Purpose:

To determine whether the dosing of intravenous (IV) induction anesthetics in patients undergoing gastrointestinal (GI) surgeries are corrected appropriately for age.

Methods:

We retrospectively reviewed the intraoperative electronic anesthetic records of 1868 adult patients (aged ≥ 18 yrs) receiving general anesthesia for GI surgeries from February 2013 - January 2014. Patients undergoing multiple procedures, those requiring temporary abdominal closure or rapid …

Evaluating Targeted And Immunomodulatory Therapies For Melanoma In A Genetically Engineered Mouse Melanoma Model, Billy Lockhart

Yale Medicine Thesis Digital Library

Melanoma therapy has changed rapidly due to the emergence of new therapies: MAPK-pathway targeted drugs and immunomodulatory agents. Given the relative success of these new individual drugs, this work set out to evaluate and develop effective melanoma treatments using combination therapies in a preclinical mouse melanoma models. Therapies tested include BRAF kinase inhibition in combination with: immune checkpoint inhibitors anti-CTLA4, anti-PDL1, and with the topical TLR7/8 agonist imiquimod. Drugs efficacies were tested in established melanomas in a conditional inducible mouse melanoma model based on activation of Braf and beta catenin and loss of Pten. 
BRAF inhibition in combination with anti-CTLA-4/anti-PD-L1 …

Simulation-Based Training In Brain Death Determination, Benjamin Macdougall

Yale Medicine Thesis Digital Library

Despite straightforward guidelines on brain death determination by the American Academy of Neurology (AAN), substantial practice variability exists internationally, between states, and among institutions. We created a simulation-based training course on proper determination based on the AAN practice parameters to address and assess knowledge and practice gaps at our institution. Our intervention consisted of a didactic course and a simulation exercise, and was bookended by before and after multiple-choice tests. The 40-minute didactic course, including a video demonstration, covered all aspects of the brain death examination. Simulation sessions utilized a SimMan 3G manikin, and involved a complete examination, including an …

Correlates Of Cocaine Use In Pregnancy, Regina Marie Melendez

Yale Medicine Thesis Digital Library

Background: Cocaine is the third most commonly used illicit substance in pregnancy. Few studies exist to specifically look for correlates of cocaine use in pregnancy.

Objective: To identify correlates of frequency of cocaine use in pregnancy

Methods: We analyzed retrospective data from 50 postpartum women with a history of cocaine use or dependence who participated in a treatment trial for postpartum cocaine use. Study variables included severity of baseline cocaine use, age of onset of use, comorbid mental illness, poly-substance use, trauma and social support history. Data were analyzed using GLMM Negative Binomial Regression.

Results: The strongest correlate of cocaine …

Symptoms Of Depression Are Linked To Subsequent Recurrent Chest Pain In Patients Admitted To An Emergency Department Chest Pain Unit., Summer Paradise

Yale Medicine Thesis Digital Library

SYMPTOMS OF DEPRESSION ARE LINKED TO SUBSEQUENT RECURRENT CHEST PAIN IN PATIENTS ADMITTED TO AN EMERGENCY DEPARTMENT CHEST PAIN UNIT. Summer A. Paradise, Matt Naftilan, James Dziura, Aini Jelani, Morgan Soffler and Basmah Safdar. Department of Emergency Medicine, Yale University, School of Medicine, New Haven, CT.

Prior studies suggest a high prevalence of depression in patients with chest pain, but few US studies have examined depression and recurrent chest pain in the emergency room setting. This study sought to compare symptoms of depression, socio-demographic features, and clinical features between low-moderate-risk emergency room (ER) chest pain center (CPC) patients with and …

A 35-Year Analysis Of Gender Trends In Radiology Authorship, Crystal Piper

Yale Medicine Thesis Digital Library

Purpose: To describe trends in authorship among female radiologists, compared to their overall representation in radiology, and to investigate the tendency of female first authors to publish with female last authors.

Material and Methods: We collected and analyzed data on gender of first and last authors for all original research and guest editorial articles from three main radiology journals - Radiology, American Journal of Roentgenology (AJR), and Academic Radiology. We restricted our analysis to authors with M.D. (medical doctorate) degrees from academic institutions within the United States. Manuscript data were collected for years 1978, 1998, 2008, and 2013. We obtained …

A Model For Short-Term Medical Service Trip Evaluation: Impact Of A Hand Surgery Trip To Honduras, Kyle Ragins

Yale Medicine Thesis Digital Library

A MODEL FOR SHORT-TERM MEDICAL SERVICE TRIP EVALUATION: IMPACT OF A HAND SURGERY TRIP TO HONDURAS.

Kyle T Ragins and J Grant Thomson. Section of Plastic and Reconstructive Surgery, Department of Surgery, Yale University, School of Medicine, New Haven, CT.

This study evaluates the impact of a hand-surgery-focused short-term medical service trip (MST) to Honduras on the upper extremity morbidity and health-related quality of life of its patients. The aim of the study is to provide a quantitative measurement of patient impact, while providing a model for how other MSTs can evaluate their outcomes to eventually determine best practices for …

Language And Health In The Hispanic/Latino Population, Gladys Rodriguez

Yale Medicine Thesis Digital Library

Hispanic/Latinos are the fastest growing racial/ethnic minority in the US and are often treated as a monolithic group in health disparities research. Language ability and preference, two distinct linguistic constructs, are some of the factors that contribute to intra-group diversity. Yet, these factors are understudied. To fill this gap, we embarked on multiple research methodologies with the goal to better understand the influence of language factors in the health experiences and health outcomes of the largest ethnic/linguistic minority in the nation.

Specifically, we explored two research questions:

1. Among Hispanic/Latino community residents with varying degrees of English language proficiency, we …

Racial/Ethnic Differences In The Presentation And Management Of Severe Bronchiolitis, Jonathan Santiago

Yale Medicine Thesis Digital Library

We examined if racial/ethnic differences exist in the presentation and management of severe bronchiolitis using a 16-center, prospective cohort study from 2007-2010. Children <2 years hospitalized with a diagnosis of bronchiolitis were included. A structured interview, chart review, and 1-week phone follow-up were completed. Multivariable logistic regression was used to examine the independent association between race/ethnicity and diagnostic imaging, treatment, management, discharge on inhaled corticosteroids, and bronchiolitis relapse. Among 2,130 patients, 818 (38%) were non-Hispanic white (NHW), 511 (24%) were non-Hispanic black (NHB), and 801 (38%) were Hispanic. Compared with all groups, NHB children were most likely to receive albuterol before admission (OR 1.58; 95%CI, 1.20-2.07) and least likely to receive chest x-rays during hospitalization (OR 0.66; 95%CI, 0.49-0.90); Hispanic children were most likely to be discharged on inhaled corticosteroids (OR 1.92; 95%CI, 1.19-3.10). We observed differences between NHW and minority children regarding pre-admission albuterol use, inpatient diagnostic imaging, and prescription of inhaled corticosteroids at discharge; practices that deviate from the American Academy of Pediatrics guidelines. The causes of these differences require further study but they support implementation of clinical care pathways for severe bronchiolitis.

The Role Of Physical Activity In The Quality Of Life Of Cancer Survivors, Apoorva Tewari

Yale Medicine Thesis Digital Library

Beyond its cardiovascular and metabolic benefits, physical activity (PA), may improve the quality of life (QOL) of cancer survivors. However, most studies have been in limited cancer types (breast, colon and prostate) and relatively little focus has been given to its effect on less common cancers. Aim 1 was to conduct a systematic review of the effect of PA on the outcomes of head and neck (H&N) cancer survivors. Aim 2 was to determine the effect of the PA guidelines from the Centers for Disease Control (CDC) on the QOL of a diverse sample of cancer survivors. To do so, …

Development, Implementation, And Evaluation Of An End Of Life Care Online Module For Pre-Clinical Students, Chung Sang Tse

Yale Medicine Thesis Digital Library

Basic palliative and end-of-life care skills are necessary for all physicians regardless of their field of specialty. Education should begin during the early stages of medical training, as early as medical school, to ensure that all physicians acquire a basic understanding of these aspects of medical care. At the Yale School of Medicine, the End-of-Life and Palliative Care Curriculum was formalized in 2008 to address this need and was expanded in 2012 to include an original educational online module. This new module was designed specifically for second-year medical students, who had the opportunity to visit hospice patients but do not …

The Hepatitis C Care Continuum Among Hiv-Infected Patients In A Large Urban Outpatient Clinic: Identifying Barriers To Achieving Optimal Outcomes, Austin Weiss

Yale Medicine Thesis Digital Library

BACKGROUND: Despite the availability of effective therapies for the treatment of chronic hepatitis C virus (HCV) infection, therapeutic benefits have yet to be experienced by patients affected by the disease, including human immunodeficiency virus (HIV) infected individuals. The aims of this study were to describe the continuum of hepatitis C care among HIV/HCV coinfected patients and identify barriers to achieving optimal management outcomes.

DESIGN AND METHODS: We conducted a retrospective analysis of HIV/HCV coinfected patients under care at an urban HIV referral clinic, comprising patients identified with HCV infection from 2002-2014. Electronic medical records of eligible patients were reviewed, capturing …

Tissue Engineering The Neural Retina With Human Embryonic Stem Cells: Exploring The Role Of The Retinal Pigment Epithelium, Yu Cheng Peter Zhao

Yale Medicine Thesis Digital Library

In order to restore vision in the late stages of retinal degeneration, it is necessary to address loss of cells from both the retinal pigment epithelium (RPE) and the neural retina. As a step towards generating neural retinal tissue for translational studies, we evaluated a biodegradable polymer scaffold as a three-dimensional vehicle for the directed differentiation of H9 human embryonic stem cells (H9-hESC) into neural retina. Polymer scaffolds were electrospun from 14% w/v polycaprolactone (PCL), approximated the thickness of native neural retina, and consisted of loose, randomly oriented fibers of subcellular diameter. H9-hESC were seeded to PCL scaffolds, cultured in …

Identification- And Singularity-Robust Inference For Moment Condition Models, Donald W.K. Andrews, Patrik Guggenberger

Cowles Foundation Discussion Papers

This paper introduces a new identification- and singularity-robust conditional quasi-likelihood ratio (SR-CQLR) test and a new identification- and singularity-robust Anderson and Rubin (1949) (SR-AR) test for linear and nonlinear moment condition models. Both tests are very fast to compute. The paper shows that the tests have correct asymptotic size and are asymptotically similar (in a uniform sense) under very weak conditions. For example, in i.i.d. scenarios, all that is required is that the moment functions and their derivatives have 2 + γ bounded moments for some γ > 0: No conditions are placed on the expected Jacobian of the moment functions, …

Nonlinear Pricing With Finite Information, Dirk Bergemann, Ji Shen, Yun Xu, Edmund M. Yeh

Cowles Foundation Discussion Papers

We analyze nonlinear pricing with finite information. A seller offers a menu to a continuum of buyers with a continuum of possible valuations. The menu is limited to offering a finite number of choices representing a finite communication capacity between buyer and seller. We identify necessary conditions that the optimal finite menu must satisfy, either for the socially efficient or for the revenue-maximizing mechanism. These conditions require that information be bundled, or “quantized” optimally. We show that the loss resulting from using the n -item menu converges to zero at a rate proportional to 1 = n 2 . We …

Why Is Pollution From U.S. Manufacturing Declining? The Roles Of Trade, Regulation, Productivity, And Preferences, Joseph S. Shapiro, Reed Walker

Cowles Foundation Discussion Papers

Between 1990 and 2008, emissions of the most common air pollutants from U.S. manufacturing fell by 60 percent, even as real U.S. manufacturing output grew substantially. This paper develops a quantitative model to explain how changes in trade, environmental regulation, productivity, and consumer preferences have contributed to these reductions in pollution emissions. We estimate the model’s key parameters using administrative data on plant-level production and pollution decisions. We then combine these estimates with detailed historical data to provide a model-driven decomposition of the causes of the observed pollution changes. Finally, we compare the model-driven decomposition to a statistical decomposition. The …

Why Is Pollution From U.S. Manufacturing Declining? The Roles Of Trade, Regulation, Productivity, And Preferences, Joseph S. Shapiro, Reed Walker

Cowles Foundation Discussion Papers

Between 1990 and 2008, air pollution emissions from U.S. manufacturing fell by 60 percent despite a substantial increase in manufacturing output. We show that these emissions reductions are primarily driven by within-product changes in emissions intensity rather than changes in output or in the composition of products produced. We then develop and estimate a quantitative model linking trade with the environment to better understand the economic forces driving these changes. Our estimates suggest that the implicit pollution tax that manufacturers face doubled between 1990 and 2008. These changes in environmental regulation, rather than changes in productivity and trade, account for …

Why Is Pollution From U.S. Manufacturing Declining? The Roles Of Environmental Regulation, Productivity, And Trade, Joseph S. Shapiro, Reed Walker

Cowles Foundation Discussion Papers

Between 1990 and 2008, air pollution emissions from U.S. manufacturing fell by 60 percent despite a substantial increase in manufacturing output. We show that these emissions reductions are primarily driven by within-product changes in emissions intensity rather than changes in output or in the composition of products produced. We then develop and estimate a quantitative model linking trade with the environment to better understand the economic forces driving these changes. Our estimates suggest that the implicit pollution tax that manufacturers face doubled between 1990 and 2008. These changes in environmental regulation, rather than changes in productivity and trade, account for …

Why Is Pollution From U.S. Manufacturing Declining? The Roles Of Environmental Regulation, Productivity, And Trade, Joseph S. Shapiro, Reed Walker

Cowles Foundation Discussion Papers

Between 1990 and 2008, air pollution emissions from U.S. manufacturing fell by 60 percent despite a substantial increase in manufacturing output. We show that these emissions reductions are primarily driven by within-product changes in emissions intensity rather than changes in output or in the composition of products produced. We then develop and estimate a quantitative model linking trade with the environment to better understand the economic forces driving these changes. Our estimates suggest that the implicit pollution tax that manufacturers face doubled between 1990 and 2008. These changes in environmental regulation, rather than changes in productivity and trade, account for …

Why Is Pollution From U.S. Manufacturing Declining? The Roles Of Environmental Regulation, Productivity, And Trade, Joseph S. Shapiro, Reed Walker

Cowles Foundation Discussion Papers

Between 1990 and 2008, air pollution emissions from U.S. manufacturing fell by 60 percent despite a substantial increase in manufacturing output. We show that these emissions reductions are primarily driven by within-product changes in emissions intensity rather than changes in output or in the composition of products produced. We then develop and estimate a quantitative model linking trade with the environment to better understand the economic forces driving these changes. Our estimates suggest that the implicit pollution tax that manufacturers face doubled between 1990 and 2008. These changes in environmental regulation, rather than changes in productivity and trade, account for …

Smarter Lunchroom Makeover Pilot- The Effect Of Subtle Nudging Strategies On Fruit And Vegetable Consumption Among Students Participating In The National School Lunch Program, Eliza Webber

Public Health Theses

Childhood obesity is on the rise in the United States, putting many of the nation’s children at an increased risk of developing serious health conditions. One way this crisis is being addressed is through efforts such as those made by the National School Lunch Program to improve children’s dietary quality by increasing the amount of fruits and vegetables provided in school meals. However, offering students more fruits and vegetables does not guarantee that they will consume more fruits and vegetables, and some critics believe these new regulations will simply lead to more meal waste without increasing students’ fruit and vegetable …

Prevalence Of Malaria And Glucose-6-Phosphate Dehydrogenase Deficiency In Malaria-Endemic Southwestern Uganda: Implications For Primaquine Use, Michelle Roh

Public Health Theses

Abstract

Introduction: Malaria transmission in Uganda is remarkably heterogeneous, and declines in prevalence have not been uniform. Previous surveys in southwestern Uganda have shown declines in parasite prevalence from 2004 to 2010. As malaria transmission continues to decline in southwestern Uganda, aggressive strategies, such as the addition of primaquine (PQ) to artemisinin-combination therapies (ACTs), are being considered in low transmission settings. Despite the potential benefit of PQ in reducing transmission, concerns over its safety and efficacy have hampered its deployment. In particular, those with glucose-6-phosphate dehydrogenase (G6PD) deficiency are at a higher risk of hemolytic toxicity.

Methods: To better assess …