Medicine and Health Sciences Commons^™

Bayesian Designs For Early Phase Clinical Trials With Novel Target Agents, Heng Zhou

Dissertations and Theses (Open Access)

My dissertation mainly focus on Bayesian designs for early phase clinical trials with novel target agents. It includes three specific topics: (1) reviewing novel phase I clinical trial designs and comparing their operating characteristics; (2) Proposing a Bayesian optimal phase II clinical trial (BOP2) design with simple and complex endpoints under a unified framework; and (3) extending the BOP2 design to incorporate the durable clinical response as a primary endpoint.

A number of novel model-based and model-assisted designs have been proposed to find the maximum tolerated dose (MTD) in phase I clinical trials, but their differences and relative pros and …

Identifying Molecular Targets And Validating Novel Therapies For Ovarian Cancer, Alejandro Villar-Prados

Dissertations and Theses (Open Access)

Re-purposing of targeted therapies for additional tumor types is a promising avenue for expanding treatment options for cancer patients, however accurately predicting what re-purposed targeted therapy will be effective remains challenging. To address this need, we developed a Therapy Predicting Tool (TPT) that accurately predicts the beneficial therapeutic effect of clinically relevant targeted therapies and the downstream pathways they may impact in the cancer of interest. Using ovarian cancer as a model to biologically validate our tool, we determined that Bromodomain and Extra-Terminal motif inhibitors (BETis), which target proteins such as BRD4, held the greatest promise to produce therapeutic effects …

Trim24 As An Oncogene In The Mammary Gland, Aundrietta Duncan

Dissertations and Theses (Open Access)

Despite the many advances made in breast cancer research and treatments, breast cancer remains one of the deadliest diseases plaguing women worldwide. While many findings on genetic mutations and their role in predisposing people to breast cancer have been uncovered, we are just beginning to understand the extent to which epigenetic regulators promote tumorigenic phenotypes, metastasis, and chemotherapeutic resistance. Moreover, new experimental tools offer the ability to address questions we were previously unable to assess. My project takes advantage of a new mouse model to understand the role of a proto-oncogenic, transcriptional co-regulator, TRIM24, in mammary gland development and disease. …

The Regulation Of Dna Methylation In Mammalian Development And Cancer, Nicolas Veland

Dissertations and Theses (Open Access)

DNA methylation is an essential epigenetic modification in mammals, as it plays important regulatory roles in multiple biological processes, such as gene transcription, maintenance of chromosomal structure and genomic stability, genomic imprinting, retrotransposon silencing, and X-chromosome inactivation. Dysregulation of DNA methylation is associated with various human diseases. For example, cancer cells usually show global hypomethylation and regional hypermenthylation, which have been implicated in genomic instability and tumor suppressor silencing, respectively. Although great progress has been made in elucidating the biological functions of DNA methylation over the last several decades, how DNA methylation patterns and levels are regulated and dysregulated is …

Development Of 3d-Printed Patient Specific Bolus For Clinical Use In To Tal Scalp Irradiation, Garrett Baltz

Dissertations and Theses (Open Access)

Total scalp irradiation (TSI) is a specialized radiation therapy technique that aims to deliver a uniform dose to the entire scalp. Original electron-based TSI techniques had limited homogeneity due to hot and cold spots created at field junctions due to the multiple matched fields that were required to treat the entire scalp. The transition to photon volumetric-modulated arc therapy based TSI techniques has improved homogeneity, to the point where non-conformal bolus is now a limiting factor. Bolus is required to build-up full dose to the scalp surface in total scalp irradiation. Creating bolus that is conformal to the scalp is …

Uncertainty In Illness And Health Literacy In Pancreatic Cancer Patients, Rae Reynolds

Dissertations and Theses (Open Access)

Background: Despite a shared link to cognitive processing of health information suggested by their definitions, information on the association between uncertainty and health literacy is scarce. Their relationship has not been studied in pancreatic cancer patients.

Aims: To evaluate uncertainty and health literacy in pancreatic cancer patients, examine their bivariate correlation, and determine significant predictors.

Methods: This descriptive, cross-sectional study was conducted in a comprehensive cancer center. Uncertainty was measured using the Mishel Uncertainty in Illness Scale -Community and health literacy was measured using the Cancer Health Literacy Test 30. Spearman’s rho tested correlation and linear regression models were …

A Behavioral Lifestyle Intervention Enhanced With Multiple-Behavior Self-Monitoring Using Mobile And Connected Tools For Underserved Individuals With Type 2 Diabetes And Comorbid Overweight Or Obesity: Pilot Comparative Effectiveness Trial, Jing Wang, Chunyan Cai, Nikhil Padhye, Philip Orlander, Mohammad Zare

Faculty, Staff and Student Publications

BACKGROUND: Self-monitoring is a cornerstone of behavioral lifestyle interventions for obesity and type 2 diabetes mellitus. Mobile technology has the potential to improve adherence to self-monitoring and patient outcomes. However, no study has tested the use of a smartphone to facilitate self-monitoring in overweight or obese adults with type 2 diabetes mellitus living in the underserved community.

OBJECTIVE: The aim of this study was to examine the feasibility of and compare preliminary efficacy of a behavioral lifestyle intervention using smartphone- or paper-based self-monitoring of multiple behaviors on weight loss and glycemic control in a sample of overweight or obese adults …

Discovery And Effects Of Pharmacological Inhibition Of The E3 Ligase Skp2 By Small Molecule Protein-Protein Interaction Disruptors, John K. Morrow

Dissertations and Theses (Open Access)

Skp2 (S-phase kinase-associated protein 2), one component of the SCF E3 ubiquitin ligase complex, directly interacts with Skp1 and indirectly associates with Cullin1 and Rbx1 to bridge the E2 conjugating enzyme with its protein substrate to execute its E3 ligase activity. Skp2 is an Fbox protein (due to it containing an Fbox domain) and it is the rate-limiting component of the SCF complex. Skp2 targets several cell-cycle regulatory proteins for ubiquitination and degradation; most notable and significant for cancer are the cyclin-dependent kinase inhibitor, p27. Skp2 is an oncogene and studies have shown that over-expression of Skp2 leads to increased …

Changes In Coronary Plaque Volume: Comparison Of Serial Measurements On Intravascular Ultrasound And Coronary Computed Tomographic Angiography, Rine Nakanishi, Anas Alani, Suguru Matsumoto, Dong Li, Michael Fahmy, Jeby Abraham, Christopher Dailing, Alexander Broersen, Pieter H Kitslaar, Khurram Nasir, James K Min, Matthew J Budoff

The Texas Heart Institute Journal

Serial measurements of coronary plaque volume have been used to evaluate drug efficacy in atherosclerotic progression. However, the usefulness of computed tomography for this purpose is unknown. We investigated whether the change in total plaque volume on coronary computed tomographic angiography is associated with the change in segment plaque volume on intravascular ultrasound. We prospectively enrolled 11 consecutive patients (mean age, 56.3 ± 5 yr; 6 men) who were to undergo serial invasive coronary angiographic examinations with use of grayscale intravascular ultrasound and coronary computed tomography, performedvolume, nor between normalized coronary plaque volume. However, in the per-patient analysis, there were …

New Pulmonary Valvuloplasty Technique By Use Of An Hourglass-Shaped Balloon In 3 Adults With Severe Pulmonary Valve Stenosis, Teoman Kilic, Tayfun Sahin, Kurtulus Karauzum, Ertan Ural, Wesley R Pedersen

The Texas Heart Institute Journal

Percutaneous balloon pulmonary valvuloplasty is the preferred therapy for pulmonary valve stenosis. However, the designs of the cylindrical balloons historically used for valvuloplasty have limitations, especially in patients who have large pulmonary annular diameters. The hourglass-shaped V8 Aortic Valvuloplasty Balloon may prove to be an effective alternative. The balloon has 2 large bulbous segments that are separated by a narrowed waist. The geometric shape is maintained throughout inflation, improving fixation and enabling broader leaflet opening. We present our first experience with the V8 balloon in 3 adults who had severe, symptomatic pulmonary valve stenosis. In addition to describing their cases, …

Cardiac Magnetic Resonance To Evaluate Percutaneous Pulmonary Valve Implantation In Children And Young Adults, Cesar Gonzalez De Alba, Fernando Molina Berganza, John Brownlee, Muhammad Khan, Dilachew Adebo

The Texas Heart Institute Journal

Experience with cardiac magnetic resonance to evaluate coronary arteries in children and young adult patients is limited. Because noninvasive imaging has advantages over coronary angiography, we compared the effectiveness of these techniques in patients who were being considered for percutaneous pulmonary valve implantation.

We retrospectively reviewed the cases of 26 patients (mean age, 12.53 ± 4.85 yr; range, 5–25 yr), all of whom had previous right ventricular-to-pulmonary artery homografts. We studied T2-prepared whole-heart images for coronary anatomy, velocity-encoded cine images for ventricular morphology, and function- and time-resolved magnetic resonance angiographic findings. Cardiac catheterization studies included coronary angiography, balloon compression testing, …

Murmur Associated With Diastolic Paradoxical Jet Flow In A 43-Year-Old Man With Hypertrophic Cardiomyopathy, Michiyo Yamano, Tatsuya Kawasaki, Hirokazu Shiraishi, Tadaaki Kamitani, Takatomo Shima, Takashi Nakamura, Satoaki Matoba

The Texas Heart Institute Journal

A diastolic paradoxical jet flow, often seen in patients with hypertrophic cardiomyopathy, is a unique flow from the apex toward the base of the left ventricle during isovolumic relaxation. To date, this phenomenon appears to have been noninvasively detected only on echocardiograms. We report the case of a 43-year-old man with hypertrophic cardiomyopathy and a diastolic paradoxical jet flow, in whom cardiac auscultation revealed a soft S4, a systolic ejection murmur, and a low-pitched early diastolic murmur immediately after S2 at the apex. On comparing his echocardiographic findings with those on phonocardiograms and apexcardiograms, we confirmed that the unusual murmur …

Public Hospitals Matter, Herbert L Fred

The Texas Heart Institute Journal

Recent events in this country pose major concerns. Police shoot unarmed blacks, gun-wielding malcontents ambush policemen, white supremacists march, gays are murdered, gender inequality pervades our workforce, and sexual harassment and abuse are surfacing in many segments of our society. In reaction, various social movements have sprung up, including Black Lives Matter, White Lives Matter, Blue Lives (policemen) Matter, Gay Lives Matter, Girls for Gender Equity (GGE), #MeToo, and Time's Up. To that list, I add another battle cry: Public Hospitals Matter.

Endoscopic Full-Thickness Resection Of A Gastric Subepithelial Tumor, Bhavtosh Dedania, Tejal Mistry, Jamie Buryanek, Shashideep Singhal

Faculty, Staff and Student Publications

No abstract provided.

Meta-Analysis Of The Effects Of Exercise Interventions On Obese Adolescents, Brandy E. Strahan Phd, Rn, Hyochol Ahn Phd, Ms-Ece, Ms-Cts, Aprn, Anp-Bc, Jonathan Shuster M.Sc., Ph.D.

Journal of Nursing & Interprofessional Leadership in Quality & Safety

A meta-analysis of 10 randomized control studies published in 2003-2013 was conducted to provide a summary of the effects of exercise interventions on obese adolescents. Outcomes of the reviewed trials included body mass index, weight, glucose, and triglycerides. Data were combined using an inverse variance weighted random effects model. The effect size estimate for BMI was 1.354 kg/m² (p < 0.001, SE 0.321), indicating that the BMI of individuals in treatment groups improved, as compared to control groups. A statistically significant reduction in weight was greater in the intervention groups than the control groups by 3.815 kg (p = 0.001, SE 1.101). The findings of this meta-analysis show that exercise interventions may improve control of weight and BMI and in turn be a factor in decreasing obesity.

Randomized Controlled Trials Evaluating Patient-Reported Outcomes After Cholecystectomy: A Systematic Review, Krislynn M Mueck, Deepa V Cherla, Amy Taylor, Tien C Ko, Mike K Liang, Lillian S Kao

Library Staff Publications

No abstract provided.

Novel Scoring System For Prediction Of Cardiac Syndrome X In Women With Typical Angina And A Positive Exercise Tolerance Test, Farzad Masoudkabir, Ali Vasheghani-Farahani, Elham Hakki, Hamidreza Poorhosseini, Saeed Sadeghian, Seyed Hesameddin Abbasi, Shahram Bahmanyar, Seyed Ebrahim Kassaian

The Texas Heart Institute Journal

A major diagnostic challenge for cardiologists is to distinguish cardiac syndrome X (CSX) from obstructive coronary artery disease in women with typical angina and a positive exercise tolerance test (ETT). We performed this study to develop a scoring system that more accurately predicts CSX in this patient population.

Data on 976 women with typical angina and a positive ETT who underwent coronary angiography at our center were randomly divided into derivation and validation datasets. We developed a backward stepwise logistic regression model that predicted the presence of CSX, and a scoring system was derived from it.

The derivation dataset (809 …

A Great Speech From A Great Man, Herbert L Fred

The Texas Heart Institute Journal

No abstract provided.

Symptomatic Celiomesenteric Trunk: Variable Presentations And Outcomes In 2 Patients, Michael L Kueht, Darrel L Wu, Joseph L Mills, Ramyar Gilani

The Texas Heart Institute Journal

Mesenteric ischemia can be difficult to diagnose without a high degree of suspicion because it presents in a variety of ways. Visceral vascular collaterals between the fore- and midgut often provide protection against ischemia; however, the presence of anatomic variations, such as celiomesenteric trunk, can undermine the expected redundancy. Misdiagnosis can result in prolonged suffering or death, as evidenced in 2 of our patients with celiomesenteric trunk. The first patient with chronic mesenteric ischemia was diagnosed in the clinic and underwent successful surgical correction; the other had overwhelming, acute mesenteric ischemia, which resulted in death. Our cases show that successful …

Cardiac Rehabilitation Improves Cardiometabolic Health In Young Patients With Nonischemic Dilated Cardiomyopathy, Samuel G Wittekind, Yvette Gerdes, Wayne Mays, Clifford Chin, John L Jefferies

The Texas Heart Institute Journal

Nonischemic dilated cardiomyopathy is deadly and costly, and treatment options are limited. Cardiac rehabilitation has proved safe and beneficial for adults with various types of heart failure. Therefore, we retrospectively evaluated the hypothesis that rehabilitation is safe and improves cardiometabolic health in young patients with nonischemic dilated cardiomypathy. From 2011 through 2015, 8 patients (4 males) (mean age, 20.6 ± 6.6 yr; range, 10-31 yr) underwent rehabilitation at our institution. They were in American Heart Association class C or D heart failure and were on maximal medical therapy. Their mean left ventricular ejection fraction at baseline was 0.26 ± 0.15. …

Effects Of Older Donor Age And Cold Ischemic Time On Long-Term Outcomes Of Heart Transplantation, Heidi J Reich, Jon A Kobashigawa, Tamar Aintablian, Danny Ramzy, Michelle M Kittleson, Fardad Esmailian

The Texas Heart Institute Journal

Using older donor hearts in cardiac transplantation may lead to inferior outcomes: older donors have more comorbidities that reduce graft quality, including coronary artery disease, hypertension, diabetes mellitus, and dyslipidemia. Shorter cold ischemic times might overcome the detrimental effect of older donor age. We examined the relationship between donor allograft age and cold ischemic time on the long-term outcomes of heart transplant recipients. rom 1994 through 2010, surgeons at our hospital performed 745 heart transplantations. We retrospectively classified these cases by donor ages of(younger) and ≥50 years (older), then by cold ischemic times of(short), 120 to 240 min (intermediate), and …

Tmc Facts & Figures, Texas Medical Center

TMC Reports

No abstract provided.

Characterizing The Information Needs Of Rural Healthcare Practitioners With Language Agnostic Automated Text Analysis, Melissa Resnick

Dissertations and Theses (Open Access)

Objectives – Previous research has characterized urban healthcare providers' information needs, using various qualitative methods. However, little is known about the needs of rural primary care practitioners in Brazil. Communication exchanged during tele-consultations presents a unique data source for the study of these information needs. In this study, I characterize rural healthcare providers' information needs expressed electronically, using automated methods.

Methods – I applied automated methods to categorize messages obtained from the telehealth system from two regions in Brazil. A subset of these messages, annotated with top-level categories in the DeCS terminology (the regional equivalent of MeSH), was used to …

Using The Literature To Identify Confounders, Scott Malec

Dissertations and Theses (Open Access)

Prior work in causal modeling has focused primarily on learning graph structures and parameters to model data generating processes from observational or experimental data, while the focus of the literature-based discovery paradigm was to identify novel therapeutic hypotheses in publicly available knowledge. The critical contribution of this dissertation is to refashion the literature-based discovery paradigm as a means to populate causal models with relevant covariates to abet causal inference. In particular, this dissertation describes a generalizable framework for mapping from causal propositions in the literature to subgraphs populated by instantiated variables that reflect observational data. The observational data are those …

A Frame-Based Nlp System For Cancer-Related Information Extraction, Yuqi Si, Kirk Roberts

Faculty, Staff and Student Publications

We propose a frame-based natural language processing (NLP) method that extracts cancer-related information from clinical narratives. We focus on three frames: cancer diagnosis, cancer therapeutic procedure, and tumor description. We utilize a deep learning-based approach, bidirectional Long Short-term Memory (LSTM) Conditional Random Field (CRF), which uses both character and word embeddings. The system consists of two constituent sequence classifiers: a frame identification (lexical unit) classifier and a frame element classifier. The classifier achieves an F

Vitamin E Status Is Inversely Associated With Risk Of Incident Tuberculosis Disease Among Household Contacts, Omowunmi Aibana, Molly F Franke, Chuan-Chin Huang, Jerome T Galea, Roger Calderon, Zibiao Zhang, Mercedes C Becerra, Emily R Smith, Carmen Contreras, Rosa Yataco, Leonid Lecca, Megan B Murray

Faculty, Staff and Student Publications

BACKGROUND: Few studies have previously assessed how pre-existing vitamin E status is associated with risk of tuberculosis (TB) disease progression.

OBJECTIVE: We evaluated the association between baseline plasma concentrations of 3 vitamin E isomers (α-tocopherol, γ-tocopherol, and δ-tocopherol) and TB disease risk.

METHODS: We conducted a case-control study nested within a longitudinal cohort of household contacts (HHCs) of pulmonary TB cases in Lima, Peru. We defined cases as HHCs who developed active TB disease ≥15 d after the diagnosis of the index patient, and we matched each case to 4 control cases who did not develop active TB based on …

Amygdala-Frontal Connectivity Predicts Internalizing Symptom Recovery Among Inpatient Adolescents, Amanda Venta, Carla Sharp, Michelle Patriquin, Ramiro Salas, Elizabeth Newlin, Kaylah Curtis, Philip Baldwin, Christopher Fowler, B Christopher Frueh

Staff and Researcher Publications

Background: The possibility of using biological measures to predict the trajectory of symptoms among adolescent psychiatric inpatients has important implications. This study aimed to examine emotion regulation ability (measured via self-report) and a hypothesized proxy in resting-state functional connectivity [RSFC] between the amygdala and frontal brain regions as baseline predictors of internalizing symptom recovery during inpatient care.

Methods: 196 adolescents (61% female; Mage = 15.20; SD = 1.48) completed the Achenbach Brief Problem Monitor (BPM) each week during their inpatient care. RSFC (n = 45) and self-report data of emotion regulation (n = 196) were collected at baseline.

Results: The …

Clinical Utility Of The Dsm-5 Alternative Model For Borderline Personality Disorder: Differential Diagnostic Accuracy Of The Bfi, Scid-Ii-Pq, And Pid-5, J Christopher Fowler, Alok Madan, Jon G Allen, Michelle Patriquin, Carla Sharp, John M Oldham, B Christopher Frueh

Staff and Researcher Publications

Background: With the publication of DSM 5 alternative model for personality disorders it is critical to assess the components of the model against evidence-based models such as the five factor model and the DSM-IV-TR categorical model. This study explored the relative clinical utility of these models in screening for borderline personality disorder (BPD).

Methods: Receiver operator characteristics and diagnostic efficiency statistics were calculated for three personality measures to ascertain the relative diagnostic efficiency of each measure. A total of 1653 adult inpatients at a specialist psychiatric hospital completed SCID-II interviews. Sample 1 (n=653) completed the SCID-II interviews, SCID-II Questionnaire (SCID-II-PQ) …

Genetic Epidemiology Of Neural Tube Defects, Philip J Lupo, A J Agopian, Heidi Castillo, Jonathan Castillo, Gerald H Clayton, Nienke P Dosa, Betsy Hopson, David B Joseph, Brandon G Rocque, William O Walker, John S Wiener, Laura E Mitchell

Faculty, Staff and Student Publications

It has been estimated that 60-70% of neural tube defects (NTDs) have a genetic component, but few causative genes have been identified. The lack of information on genes associated with non-syndromic NTDs in humans is especially notable as the "genomic revolution" has led to new tools (e.g., genome-wide genotyping arrays, next-generation sequencing) that are helping to elucidate the full spectrum of genetic variation (from common to rare) contributing to complex traits, including structural birth defects. However, the application of modern genomic approaches to the study of NTDs has lagged behind that of some other common structural birth defects. This may …

Impact Of Terminology Mapping On Population Health Cohorts Impact, Barbara A. Berkovich

Dissertations and Theses (Open Access)

Background and Objectives: The population health care delivery model uses phenotype algorithms in the electronic health record (EHR) system to identify patient cohorts targeted for clinical interventions such as laboratory tests, and procedures. The standard terminology used to identify disease cohorts may contribute to significant variation in error rates for patient inclusion or exclusion. The United States requires EHR systems to support two diagnosis terminologies, the International Classification of Disease (ICD) and the Systematized Nomenclature of Medicine (SNOMED). Terminology mapping enables the retrieval of diagnosis data using either terminology. There are no standards of practice by which to evaluate and …