Medicine and Health Sciences Commons^™

Cost-Benefit Analysis Of A Pediatric Patient Blood Management Program, Karen D. Gibbs

Dissertations & Theses (Open Access)

Introduction

Red blood cell (RBC) transfusions can be a life-saving and important intervention used to replace blood loss or manage anemia, but they also come with risks from transfusion-associated adverse events (TAAEs). Patient blood management (PBM) involves a multidisciplinary approach to optimize care of patients who may need a transfusion, including blood conservation modalities, patient-centered decision making, among others. The impact of PBM in the pediatric setting is not well understood, particularly the impact on TAAEs and the economic impact of these programs.

The following specific aims were pursued: (1) To investigate the effect of a PBM program on transfusion …

Good Faith: Surveillance And Evaluation Of 911 Good Samaritan Laws In The United States, Shane W. Reader

Dissertations & Theses (Open Access)

To fight soaring overdose mortality rates in the United States, lawmakers adopted a variety of harm reduction tools. Among these, 911 Good Samaritan Laws (GSLs) derive their name from the biblical parable of the Good Samaritan, a bystander who broke cultural convention to come to the aid of a man beset by thieves. These laws provide limited criminal immunity for bystanders in possession of controlled substances to encourage them to report drug overdoses. While previous studies associate GSLs with a modest reduction in opioid mortality, analyses often model them as equivocal or divide them coarsely across individual provisions. Evaluating these …

Concomitant Inhibition Of Flt3 And Mcl-1 In Flt3 Mutated Acute Myeloid Leukemia, Paul Panis

Dissertations & Theses (Open Access)

The MCL-1 inhibitor S63845 synergizes with the FLT3 inhibitor midostaurin for potent anti-leukemic effect in preclinical human models of FLT3-ITD mutated acute myeloid leukemia (AML). Acute Myeloid leukemia (AML) is a neoplastic blood disorder defined by a characteristically rapid growth rate and altered behavior of myeloid cells in the bone marrow. The FLT3 receptor is responsible for the upstream regulation of many key processes in hematopoietic cells. FLT3 internal tandem duplication (ITD) mutations are common in leukemia and have been observed in up to a third of newly diagnosed AML patients. FLT3-ITD have been implicated as a driver mutation partly …

Quantifying The Magnitude Of Total Dose Deviation Caused By Various Sources Of Error Among Iroc Phantom Irradiation Results, Sharbacha S. Edward

Dissertations & Theses (Open Access)

The Imaging and Radiation Oncology Core (IROC) phantoms are used as an end-to-end test of an institution’s radiotherapy processes, and for clinical trial credentialing. Phantoms are treated like patients, and evaluation of the doses received by the thermoluminescent dosimeters (TLDs) inside the phantom, reflects the accuracy with which an institution can image, plan and irradiate a phantom or patient. Recent phantom results show that among the hundreds of various IROC phantoms irradiated annually, 8-17% of institutions fail this test. The purpose of this work was to investigate the various types of errors that may occur during the treatment process and …

Individual Differences In Lpp Amplitude And Theta Power Predict Cue-Induced Eating During A Cued Food Delivery Task, Kyla Gibney

Dissertations & Theses (Open Access)

Due to individual differences in the brain’s reward system, some individuals are more vulnerable than others to maladaptive, reward-seeking behaviors, such as substance use or compulsive eating. A body of research has demonstrated that individuals who attribute higher levels of incentive salience to reward-associated cues than to pleasant images (termed “C>P group” throughout) are more vulnerable to compulsive eating than those who attribute higher incentive salience to pleasant images than reward- associated cues (P>C group). Meanwhile, a separate body of research has demonstrated that cognitive control also regulates eating by enabling top-down attentional control. This dissertation aims to …

Med12 Is A Critical Regulator Of Neural Crest Lineage And Nervous System Myelination, Fatma Betul Aksoy Yasar

Dissertations & Theses (Open Access)

The Mediator complex (MED) is a multi-subunit protein complex integral to the eukaryotic transcription machinery. MED12 is a Cdk8- regulatory kinase module subunit directly implicated in human disease and is genetically altered in neurological disease and cancer. Numerous attempts at generating an in vivo system to study the role of Med12 failed due to embryonic lethality associated with germline or developmental disruption of Med12 gene. To understand the cellular and molecular processes associated with its role in disease, we generated multiple mouse models with targeted depletion of MED12 in distinct cellular lineages. Our genetically engineered models with induced and conditional …

Risk-Factor Induced Changes In The Breast Microenvironment Facilitate Inflammatory Breast Cancer Progression And Lymphovascular Invasion, Wintana Balema, Wintana Balema

Dissertations & Theses (Open Access)

Inflammatory breast cancer (IBC) is a rapidly progressing, rare and highly lethal form of breast cancer. IBC is a clinical diagnosis, requiring >1/3 involvement on the affected breast and/or skin by erythema, and disease onset of < 6 months. The clinical symptoms of IBC vary in severity and presentation, these include redness, warmth, skin thickening and bruised or pink/purple discoloration appearance and skin changes such as peau d’orange. These skin symptoms are not attributed to inflammation, rather IBC is characterized by florid lymphovascular tumor emboli clogging dermal lymphatics. This leads to “classic” symptoms of breast swelling and skin edema or discoloration. To date, unique genomic drivers which differentiate IBC from non-IBC invasive breast cancers have not been identified highlighting a role for the microenvironment. Several epidemiological studies have unveiled subtype-specific risk factors associated with IBC that are known to alter the microenvironment. Obesity is an established risk factor for all subtypes of IBC. Never-breastfeeding increases risk for developing the most aggressive, triple-negative IBC. Further, never breastfeeding is associated with later clinical stage and worse outcomes. We worked to model these overlapping risk factors to understand microenvironment changes that may lead to the lymphatic change’s indicative of IBC.

First, we investigated the association of a “classic” triad of clinical IBC signs with overall survival among patients to demonstrate the most overt clinical findings of lymphatic involvement were impacting prognosis. We evaluated a triad of IBC signs, including swollen involved breast, nipple change, and diffuse skin change, using breast medical photographs from patients enrolled on a prospective IBC registry. We reported that the …

Ankyrin Dependent Mitochondrial Function And Bioenergetics In The Heart, Janani Subramaniam, Janani Subramaniam

Dissertations & Theses (Open Access)

ANK2 mutations in patients are associated with numerous arrhythmias, cardiomyopathies, and other heart defects. In the heart, AnkB, the protein encoded by ANK2, clusters relevant ion channels and cell adhesion molecules in several important domains; however, its role at Mitochondria Associated ER/SR Membranes (MAMs) has yet to be investigated. MAMs are crucial to mitochondrial function and metabolism and are signaling hubs implicated in various cardiac pathologies. Among several functions, these sites mediate the direct transfer of calcium from the ER/SR to the mitochondria to modulate ATP synthesis. Given that mitochondrial function and energy production are paramount to cardiovascular heath, …

Visualization Literacy And Decision-Making In Healthcare, Stacy Weil

Translational Projects (Open Access)

The ability of workers in the healthcare industry to analyze, interpret and communicate with health data is critical to decision-making and impacts both health and business outcomes. Optimal decision-making requires having real-time access to information that provides useful insights and that lends itself to collaborative decision-making. Data visualizations have the potential to facilitate decision-making in healthcare when presented as a dashboard. However, dashboards have shown varying results in both effectiveness and adoption. Data or graphical literacy challenges experienced by health team members could complicate strategic decision-making through an inability to correctly interpret or summarize the information presented in a dashboard. …

Usability And Technology Acceptance Of An Electronic Child Abuse Screening Tool In A Pediatric Emergency Department, Angela Hayes

Translational Projects (Open Access)

Up to half of all child physical abuse victims with major abuse injuries seen in hospitals had sentinel injuries assessed by medical providers. Universal screening for child abuse and neglect in the emergency department can potentially increase detection at lower levels of injury. However, we must consider usability for the electronic health record embedded child abuse and neglect-screening tool to be most effective. The user most likely to interact with the screening tool is the bedside nurse. The interface of the initial screening tool and the process of inputting information must be perceived as useful, usable, and satisfying to the …

Investigating Fruit And Vegetable Variety In A National Food Co-Op: A Brighter Bites Evaluation, Katherine G. Hearne

Dissertations & Theses (Open Access)

American children eat fewer fruits and vegetables (F&V) and less variety of F&V than recommended for health. Food cooperatives and other programs have become a popular way to increase F&V intake, but little is known about the variety of F&V distributed by these programs or its relationship with program attendance or child F&V intake. Brighter Bites is a national, school-based food co-op distributing rescued, donated, fresh F&V to families in low-income schools. We evaluated, for the first time, the variety of F&V Brighter Bites distributed to families in the 2018-2019 school year and the relationships between that variety and both …

Perceptions And Roles Of Genetic Counselors In Perinatal Palliative Care: Where Are We Now?, Amanda Chamberlain

Dissertations & Theses (Open Access)

After the identification of a life-limiting fetal diagnosis, a perinatal palliative care (PPC) team can provide specialized medical care and emotional support for the family throughout the pregnancy and after delivery. Although the growth of the field of PPC over the last ten years is well-documented, there is only one study to date that explores the experiences of genetic counselors with regards to PPC. This study seeks to further the understanding of genetic counselors’ current perceptions of, experiences with, and roles in the delivery of PPC.

An edited version of the Perinatal Palliative Care Perceptions and Barriers Scale was used …

Absolute Quantification Of Tc-99m Activity Distributions Using A Planar Molecular Breast Imaging Commercial System, Benjamin P. Lopez

Dissertations & Theses (Open Access)

Molecular breast imaging (MBI) uses two dedicated-breast semiconductor detectors to visualize the preferential uptake of technetium-99m-sestamibi (^99mTc-sestamibi) by breast cancer cells relative to surrounding benign breast tissues. Clinically, MBI is used primarily as a supplementary tool to standard-of-care mammography because of its improved detection of breast cancers, especially in women with mammographically-dense breasts. Because of a lack of image corrections, MBI applications are currently limited to qualitative evaluations of relative pixel intensities between image regions with suspected lesions and normal tissue.

The objective of this dissertation was to use Monte Carlo simulations to better characterize the MBI imaging …

Defining The Cooperation Between Mhc-I And Mhc-Ii Neoantigen-Driven T Cell Responses To Develop Effective Personalized Immunotherapies, Charmelle Williams

Dissertations & Theses (Open Access)

Immune checkpoint therapy (ICT) (e.g. anti-CTLA-4 (α-CTLA-4), anti-PD-1 (α-PD-1)) enables durable T cell-dependent anti-tumor immunity in certain cancer patients. Since a subset of patients respond to ICT, this work aims at developing a more in-depth understanding of T-cell responses to MHC class I (MHC-I) and MHC class II (MHC-II) tumor antigens that are derived from aberrant expression of non-mutant antigens or driver and passenger somatic alterations that can function as tumor neoantigens. We used a poorly immunogenic Braf^v600e Pten^-/- Cdkn2a^-/- YUMM1.7 (Y1.7) murine melanoma line with a paucity of endogenous neoantigens that is unresponsive to ICT, and …

Yap And Taz Are Required For Neural Crest-Derived Cardiovascular Development, Shannon Erhardt

Dissertations & Theses (Open Access)

Congenital heart defects (CHDs) are the most common human birth defect, occurring in ~1/100 newborns, and are a leading cause of early infant death. Cardiac neural crest cells (NCCs) are a migratory and multipotent cell population known to aid in the development of the cardiac outflow tract (OFT), valves, and interventricular septum, during embryogenesis. Yap and Taz are downstream effectors of the fundamental Hippo signaling pathway and are vital for proper organ and tissue development, yet their role in neural crest (NC)-derived heart formation is still largely unknown. We generated Yap and Taz conditional knockout (CKO) mice using a Cre-lox …

The Role Of The Hypoxia-Inducible Factor 2 In Pancreatic Cancer: Mechanisms Of Tumor Immunosuppression And Intestinal Radioprotection, Carolina Garcia Garcia

Dissertations & Theses (Open Access)

Pancreatic ductal adenocarcinoma (PDAC) is a devastating disease with dismal prognosis. The only curative option for patients is surgery, but over 80% of patients are not surgical candidates. Unfortunately, PDAC is resistant to the three remaining options. PDAC is characterized by a profoundly hypoxic and immunosuppressive stroma, which contributes to its therapeutic recalcitrance. Alpha-smooth muscle actin+ (αSMA+) cancer-associated fibroblasts (CAFs) are the most abundant stromal component, as well as mediators of stromal deposition. The hypoxia-inducible factors (HIF1 and HIF2) coordinate responses to hypoxia, yet, despite their known association to poor patient outcomes, their functions within the PDAC tumor microenvironment (TME) …

Roles Of Oxidative Stress And Dna Methylation In Cigarette Smoking-Induced Accelerated Acute Myeloid Leukemia Progression, Mary Figueroa

Dissertations & Theses (Open Access)

Acute myeloid leukemia (AML) is a commonly diagnosed cancer in smokers. When current or former smokers have AML, they have worse survival compared to never smoking patients. This has been observed clinically for decades, but then it is unknown how smoking leads to worsened AML survival. Smoking causes oxidative stress and altered DNA methylation that persists for decades in peripheral blood mononuclear cells, but these changes from smoking have not been evaluated in the context of AML. We hypothesize that smoking-induced molecular changes, including altered DNA methylation associated with poor AML prognosis, promote AML. We developed a novel model to …

Induced Cytotoxicity In Crebbp/Ep300mut Head And Neck Squamous Cell Carcinoma, Thomaia Pamplin

Dissertations & Theses (Open Access)

INDUCED CYOTOXICTY IN CREBBP/EP300mut HEAD AND NECK SQUAMOUS CELL CARCINOMA

Thomaia Pamplin

Advisor: Curtis Pickering, Ph.D.

Background: Head and neck squamous cell carcinoma HNSCC is the most common malignancy in the head and neck. Most cases are found in advanced stages and depending on the location can be treated with surgical resection and/or radiation (XRT), chemotherapy, or chemoradiation. Our lab groups have identified that HNSCC with a mutation in its CREBBP/EP300 genes can be sensitized to XRT when the histone acetyltransferase activity of CREBBP/EP300 is inhibited. This radiosensitization manifests in the form of increased cell death for …

A Microfluidics-Based Approach For Isolation Of Antigen-Specific Cd8+ T Cells, Meredith Frank

Dissertations & Theses (Open Access)

Cancer is a global epidemic: there are predicted to be 200 million new cases this year alone. Almost a quarter of all cancer-related deaths are caused by lung cancer, for which 5-year survival rates are just above 20%. 85% of lung cancer diagnoses are classified as non-small cell lung cancer (NSCLC) for which 5-year survival rates in metastatic disease are less than 10%. Early detection and targeted therapies have improved prognoses, yet relapse is still common among patients.

Immunotherapies that leverage tumor-specific CD8⁺ cytotoxic T cells have shown great promise for the treatment of NSCLC. However, although highly promising, …

The Novel Role Of Dnmbp In Kidney Development, Brandy Walker

Dissertations & Theses (Open Access)

Congenital anomalies of the kidney and urinary tract (CAKUT) accounts for nearly one-fourth of all birth defects and more than 40% of pediatric end-stage renal disease, yet only 10-20% of CAKUT cases have a known monogenetic cause. Human kidneys are composed of up to a million epithelial tubules called nephrons. Disruption of nephron development is one of the many congenital anomalies that cause CAKUT, often resulting in chronic or end-stage renal disease which requires transplant. During nephron epithelialization, the formation of stable cadherin-mediated adhesion junctions is essential for maintaining cell-cell contacts. To understand the cell behaviors underlying abnormalities in renal …

Unraveling The Effects Of Aerobic Exercise And Erk5 Signaling In The Solid Tumor Microenvironment Using Murine Models, Hannah Savage

Dissertations & Theses (Open Access)

Solid tumors are comprised of multiple cell types which communicate and work together to promote tumor progression. Advances in the treatment of solid tumors have armed clinicians with more efficacious pharmacologic agents and combinations. However, a focus on drug adjuvants in the treatment of solid cancer has left gaps in knowledge regarding non-pharmacologic treatment adjuvants, like aerobic exercise. The current dissertation investigates pharmacologic and non-pharmacologic based approaches to remodel the solid tumor microenvironment landscape and alter therapeutic efficacy. We disassemble compartments of the tumor microenvironment, including tumor vasculature and immune infiltrate, using mouse models and single cell techniques, to elucidate …

Bhlhe40: Required For Tumor Microenvironment Remodeling And Immune Checkpoint Therapy Efficacy, Avery Salmon, Avery J. Salmon

Dissertations & Theses (Open Access)

Advancements in immunotherapy treatments have become essential in the treatment of various cancers, such as those with high tumor burden like melanoma(Brahmer et al., 2012; Hodi et al., 2010). Immunotherapy, specifically immune checkpoint therapy (ICT) provides antagonist effect on specific immune checkpoints to control effector T cell functions(Pardoll, 2012). This therapy allows for the modulation of anti-tumor responses through the use of monoclonal antibodies, such as anti-CTLA-4 or anti-PD-1 that block the receptors from binding with their ligands, thus allowing for CD4⁺ and CD8⁺ T cell priming and activation(Wei et al., 2017). However, the required epigenetic and transcriptional …

Development Of Graphical Models And Statistical Physics Motivated Approaches To Genomic Investigations, Yashwanth Lagisetty

Dissertations & Theses (Open Access)

Identifying genes involved in disease pathology has been a goal of genomic research since the early days of the field. However, as technology improves and the body of research grows, we are faced with more questions than answers. Among these is the pressing matter of our incomplete understanding of the genetic underpinnings of complex diseases. Many hypotheses offer explanations as to why direct and independent analyses of variants, as done in genome-wide association studies (GWAS), may not fully elucidate disease genetics. These range from pointing out flaws in statistical testing to invoking the complex dynamics of epigenetic processes. In the …

Cell-Free Dna Sequencing In Multiple Myeloma, Russell Irwin

Dissertations & Theses (Open Access)

Multiple myeloma (MM) is an incurable plasma cell dyscrasia. Recent advances in MM therapy, including CAR-T therapy, have increased survival and shown the value of assessing treatment response with great sensitivity, both in acute and long-term settings. Cell-free DNA, DNA fragments which are released into circulation as a part of normal cellular turnover, is a useful and dynamic biomarker in cancer patients due to the presence of circulating tumor DNA (ctDNA), which is readily identified using next generation sequencing. Here we report the analytical sensitivity, applicability, consistency, and prognostic ability of M5Seq, a novel hybrid capture panel designed for MM …

Development Of Advanced Mr-Guided Adaptive Radiation Therapy Methods For Head & Neck Cancers On The 1.5t Mr-Linac, Brigid Mcdonald

Dissertations & Theses (Open Access)

The 1.5T hybrid MRI/linear accelerator (MR-linac) has recently been introduced into clinical practice and used for the treatment of head and neck cancers (HNC). This device enables on-line adaptive radiation therapy (ART) based on anatomical changes throughout treatment and variations in patient position. This novel technology also has the potential for advanced ART strategies such as dose-optimized ART, in which the treatment plan is optimized based on the accumulated dose over previous fractions, or biological image-guided ART, in which the plan is adapted based on individual tumor response as measured through quantitative imaging techniques such as diffusion-weighted imaging (DWI). The …

Listening To Remotely Monitored Home-Based Preferred Music For Pain In Older Adults With Low Back Pain: A Pilot Study Of Feasibility And Acceptability, Setor Kofi Sorkpor

Dissertations & Theses (Open Access)

Background: Low back pain (LBP) is a complex, multifaceted, and widespread condition that impairs the quality of life of older adults aged 65 years or older. Although nonpharmacologic interventions informed by the biopsychosocial model are recommended as first-line therapy for LBP, pharmacologic therapies, including opioids, are commonly used as first-line interventions in practice. This could be attributed to a lack of understanding of the analgesic properties of most nonpharmacologic interventions. Nonetheless, some nonpharmacologic therapies, such as passive music listening, have been shown to modulate pain via pathways that target the neurophysiological mechanisms associated with pain.

Specific Aims: The specific aims …

Social Network Analysis Of Online Support Communities For Adolescent And Young Adult Cancer Survivors, Carlos Perez Aldana

Dissertations & Theses (Open Access)

There are an estimated 633,000 adolescent and young adult (AYA) cancer survivors in the U.S. and nearly 89,500 AYAs are diagnosed with cancer every year. Cancer creates developmental and life stage disruptions, which result in multiple survivorship challenges, particularly among AYAs. Despite the advances made in cancer oncology and survivorship care, AYA cancer survivors continue to face diverse and unique psychosocial needs. Research suggests that online support communities have the potential to positively impact psychosocial care by providing AYA cancer survivors with access to social support which can help them successfully transition from treatment back to normal life as well …

Leveraging Single Cell Technologies For The Characterization And Treatment Of Refractory Pancreatic Cancer, Maria Monberg

Dissertations & Theses (Open Access)

Heterogeneity is a hallmark of cancer, and the advent of multimodal single-cell technologies has helped uncover heterogeneity in a high-throughput manner in different cancers across varied contexts at an unprecedented resolution. In an effort to improve precision medicine approaches in pancreatic ductal adenocarcinoma (PDAC), a highly lethal malignancy with a mere 11% 5-year survival rate, this dissertation focuses on first questioning the assumptions of the most basic models used to study PDAC via multimodal single-cell characterization methods at multiple levels of biological organization (scCNVseq and snATACseq for DNA assays, scRNAseq for transcriptomics, and paired protein assays such as multiplexed immunofluorescence …

Postpartum Depression Screening In The Neonatal Intensive Care Unit: Maternal And Provider Perspectives, Candice Triulzi

Dissertations & Theses (Open Access)

Objective: Although mothers of preterm infants are at increased risk for postpartum depression (PPD), PPD screening conducted by neonatal providers in the Neonatal Intensive Care Unit (NICU) is currently not a standard of care. The purpose of this study was to explore maternal and provider perceptions of neonatal providers conducting PPD screening in the NICU.

Design: This study was conducted with a qualitative approach.

Setting: A 24-bed Level III NICU in Houston, TX acted as the study site.

Participants: Participants were purposively sampled (N=31) and included mothers of NICU infants (n=15) and NICU providers (n=16).

Methods: Semi-structured individual and paired …

Perceptions Of Integrating Immersive Virtual Reality Simulation As A Teaching Methodology In A Hospital Setting, Ladonna Christy

Dissertations & Theses (Open Access)

Introduction As newly licensed nurses enter the workforce with limited experience and limited clinical reasoning skills, nursing educators must employ innovative strategies to teach graduate nurses how to identify and manage clinical deterioration – skills which are vital to saving lives and improving outcomes. Fully immersive Virtual Reality (VR), (also defined as Immersive VR) is one effective educational strategy available for hospital educators to use for preparing newly licensed nurses to recognize and manage clinical deterioration.

Objective The purpose of this study was to explore perceptions of hospital-based nurse educators, simulation specialists, and nursing leaders with respect to integrating immersive …