Medicine and Health Sciences Commons^™

Frozen By Worry And Fatigue? A Mixed Methods Approach To Understanding The Lived Experiences Of Freezing Of Gait, Sarah M. Ghose

Theses and Dissertations

This study utilized a mixed methods emergent, phenomenological approach to (1) understanding the lived experience of freezing of gait for individuals diagnosed with Parkinson’s Disease and (2) determining the role of anxiety and sleep in freezing of gait outcomes. Participants included 13 adults diagnosed with Parkinson’s Disease (N=14 for qualitative data, N=13 for quantitative data; 23.1% female-identifying, 76.9% male-identifying) who were predominantly white (92.3%) with an average age of 69 years (SD = 6.73 years). Data collection consisted of semi-structured interviews, self-report measures, actigraphic sleep data, and salivary alpha amylase biomarker collection. Results are organized into …

Molecular Mechanisms Of Prdm16 As A Tumor Suppressor In Pancreatic Ductal Adenocarcinoma, Eric Hurwitz

Theses and Dissertations

The transcription factor Prdm16 functions as a potent suppressor of transforming growth factor-beta (TGF-b) signaling, whose inactivation is deemed essential to the progression of pancreatic ductal adenocarcinoma (PDAC). Using the Kras^G12D-based mouse model of human PDAC, we surprisingly found that ablating Prdm16 did not block but instead accelerated PDAC formation and progression, suggesting that Prdm16 might function as a tumor suppressor in this malignancy. Subsequent genetic experiments showed that ablating Prdm16 along with Smad4 resulted in a shift from a well-differentiated and confined neoplasm to a highly aggressive and metastatic disease, which was associated with a striking deviation …

Prospective Investigation Of Insomnia Symptoms And Sleep Duration As Risk Factors For Stroke Incidence And All-Cause Mortality In U.S Adult, Wendemi Sawadogo

Theses and Dissertations

Background and Objectives: Stroke is the second leading cause of death in the world. In the United States, on average, someone has a stroke every 40 seconds and someone dies as a result of stroke every 3.5 minutes. Identifying modifiable risk factors of stroke is therefore a public health priority. The purpose of this study was to investigate the extent to which insomnia symptoms and sleep duration contribute to stroke incidence, all-cause mortality, and explore potential causal pathways.

Methods: The Health and Retirement Study (HRS) and the REasons for Geographic And Racial Differences in Stroke (REGARDS) study were …

Contribution Of Metabolic Cell Swelling On Microcirculatory Perfusion In Septic Shock, Charles E. Payne

Theses and Dissertations

Sepsis, a systemic immunological response that leads to organ-dysfunction, the development of septic shock, and death has mortality rate of 15-25%. A subset of sepsis, septic shock, has an in-hospital mortality rate of 30-50%. Sepsis and its treatment are the most expensive healthcare problem in the United States with the US Agency for Healthcare Research and Quality estimating annual costs over $20 billion. Hypoxia experienced in septic shock induces metabolic cell and tissue swelling leading to further microcirculatory dysfunction and poor tissue perfusion. Reversing metabolic cell swelling corrects these perfusion defects. Two models were used in rats to induce septic …

A Learning Health System For Radiation Oncology, Rishabh Kapoor

Theses and Dissertations

The proposed research aims to address the challenges faced by clinical data science researchers in radiation oncology accessing, integrating, and analyzing heterogeneous data from various sources. The research presents a scalable intelligent infrastructure, called the Health Information Gateway and Exchange (HINGE), which captures and structures data from multiple sources into a knowledge base with semantically interlinked entities. This infrastructure enables researchers to mine novel associations and gather relevant knowledge for personalized clinical outcomes.

The dissertation discusses the design framework and implementation of HINGE, which abstracts structured data from treatment planning systems, treatment management systems, and electronic health records. It utilizes …

Addressing Death Distress In Caregivers Of Patients With Malignant Glioma, Kelcie D. Willis

Theses and Dissertations

The field of psychosocial oncology seeks to improve the quality of life of patients and families affected by cancer. This task becomes increasingly important when there are limited, non-curative treatment options, a high probability of recurrence, and rapid functional decline, such as in the case of a malignant glioma (MG). Indeed, the diagnosis of a MG is associated with negative sequalae that often translates to higher caregiver burden. Caregivers—who must manage the functional decline of the patient, changes within the family, and a complicated medical system—often feel overwhelmed, isolated, and ill-equipped to handle these myriad responsibilities. While they also report …

Isoprenylation Inhibition Significantly Reduces Ige Mediated Mast Cell Function And Allergic Disease, Jordan Dailey

Theses and Dissertations

Allergic disease is the 6^th leading cause of chronic illness in the US and accounts for billions of dollars in healthcare annually. Mast cells are tissue resident innate immune cells linked to allergic disease and activated by IgE and other ligands. Upon activation, they release histamine, cytokines, chemokines, proteases, and lipid mediators evoking allergic symptoms. New ways of targeting mast cells could greatly benefit allergic disease therapy. Previous findings supported repurposing statin drugs, such as Fluvastatin, as a therapeutic treatment of allergic disease reduced allergic symptoms in vitro and in vivo. We found that Fluvastatin suppressed IgE-mediated mast cell …

Characterization Of A Solid-State Detector For Dosimetry In The Diagnostic Energy Range With Verification Via Monte Carlo Estimation Of Average Breast Dose In Mammography, Areej Aljabal

Theses and Dissertations

This dissertation aims to develop a simplified QA metric for estimating radiation dose in mammography. This metric, the Mid-Breast Dose (MDB) Index, maybe be proposed as an alternative dose index, consistent with average glandular dose (AGD), for routine QA. MBD was obtained using “Phantom mid-point Air Kerma (AK) measurement” for conventional mammography. The advantage of this method is that MBD can be measured directly without requiring multiple conversion factors. The accuracy of clinical measurements in computing the MBD was assessed by comparing it with the AGD estimated by the Dance formalism experimentally and Monte Carlo simulation.

MBD methodology relies on …

Characterization And Investigation Of Cold Atmospheric Plasma And Its Effects On Cancer Cell Biology, Thomas M. Ritrosky

Theses and Dissertations

Modern cancer treatment uses radiation therapy in over 50% of patient cases. It is an e↵ective way of treating tumors because the mechanisms of cell killing are well known through the damage that ionizing radiation does to DNA. The amount of radiation can be tracked through measuring the dose of the clinical photon or electron beam used. However, there are limitations in the usage of radiation therapy, for example, a tumor can create hypoxic areas that become radioresistant leading to complete ine↵ectiveness of further radiation treatment. This project looks into the application of cold atmospheric plasma as an adjuvant therapy …

Role Of Histone Deacetylase (Hdac) In Epithelial To Mesenchymal Transition (Emt) In A Human Cholangiocyte Model Of Ischemic Cholangiopathy, Priyanshi Pragnesh Parikh

Theses and Dissertations

Organ transplants are a vital intervention for many diseases that result in end stage organ failure. Currently, the donation pool is not meeting the demands of the transplant list. Expanding this pool to include donation after cardiac death (DCD) is highly sought-after. However, the use of DCD livers can lead to increased odds of graft failure and ischemic cholangiopathy. The loss of epithelialization and fibrosis that occurs during ischemic cholangiopathy is characteristic of these cells undergoing epithelial-to-mesenchymal transition (EMT). The biological changes the cell experiences enhance migratory capacity, invasiveness, and increased resistance to apoptosis. Our earlier studies have shown differential …

Characterizing The Effects Of Antiandrogens And Senolytics To Enhance The Therapeutic Response To Castration-Resistant Prostate Cancer, Justin M. Silverman

Theses and Dissertations

Prostate cancer is the most frequently diagnosed cancer in males and the second most common cause of cancer deaths. Androgen deprivation therapy, whether through surgical or chemical castration, is the mainstay for treatment of advanced prostate cancer; however, despite an initial response, most patients eventually develop a progressive PSA rise, and castration- sensitive prostate cancer gives rise to castration-resistant prostate cancer. The standard of care therapy includes the antiandrogens such as enzalutamide and abiraterone acetate as well as the microtubule poison, docetaxel, and various immunotherapies; however, while prostate cancer research is progressing, there continues to be a compelling need for …

Modeling Of Patient-Specific Periaortic Mechanics And Pulmonary Artery Hemodynamics Based On Phase-Contrast Magnetic Resonance Imaging Sequences., Johane H. Bracamonte

Theses and Dissertations

Inverse modeling in cardiovascular medicine is a collection of methodologies that can provide non-invasive patient-specific estimations of clinical risk factors using medical imaging as inputs. Its incorporation into clinical practice has the potential to improve diagnosis and treatment planning with low associated risks and costs.

Herein, three different phase contrast magnetic resonance imaging (MRI) modalities were implemented as input data, displacement encoding with stimulated echoes (DENSE MRI) applied, and time-resolved velocity encoding phase-contrast MRI, in 1D and 3D, applied to pulmonary artery (PA) hemodynamics.

A model to account for the effect of periaortic interactions due to static and dynamic structures …

Theta Burst Brain Stimulation In Painful Diabetic Neuropathy Patients: Investigating Neural Mechanisms, Bhushan Thakkar

Theses and Dissertations

Chronic pain (CP) is a significant contributor to disability and disease burden globally. In 2019, approximately 50.2 million adults (20.4% of the US population) experienced chronic pain, contributing to $560-635 billion in direct medical costs. In addition, the worldwide prevalence of diabetes mellitus has reached epidemic proportions and is set to increase to 629 million by 2045. Almost 50% of patients with diabetes present with diabetic neuropathy (DN), and one in five patients with diabetes presents with painful DN (pDN) which is the most common cause of neuropathic pain (NP) in the US. Symptomatic treatment is the mainstay of management …

A Method For Predicting Dose Changes For Hn Treatment Using Surface Imaging, Sarah E. Holler

Theses and Dissertations

Head and neck cancer is commonly treated with a six- to seven-week course of radiotherapy, during which a patient’s anatomy may change substantially, due to target reduction or weight loss. Anatomical changes lead to reduction in treatment quality due to decreased setup reproducibility and altered dose deposition compared to the original plan. Few clinics have developed a standard method for triggering resimulation and replan due to anatomic changes. This work investigates a new method for determining when to resimulate and replan HNC patients by utilizing their topographic anatomical changes to predict differences in planned versus delivered dose distributions. The first …

Tummy Time In Infancy: Real-World Assessments And Associations With Developmental Outcomes In Early Childhood, Ketaki Inamdar

Theses and Dissertations

Tummy time or awake, supervised, prone play is an important developmental play position in infancy. Engaging in more than 15 minutes of tummy time per day is associated with a lower risk of plagiocephaly, lower body mass index, and achievement of higher motor scores in full-term and at-risk preterm infants. However, there are significant gaps in the measurement of tummy time in current literature. Conventionally used subjective parent reports have not been validated against gold standard direct observation, and the feasibility and real-world validity of objective solutions such as wearable sensors has not been examined in full-term and at-risk preterm …

Changes In Physical Activity And Relationships To Submaximal Exercise Capacity And Cardiac Function During Breast Cancer Therapy, Moriah P. Bellissimo

Theses and Dissertations

Background: Breast cancer (BC) survivors are at high risk for heart failure due to curative cancer therapies. In non-cancer populations, physical activity is a first line treatment for preventing cardiovascular disease. This study examined whether more physical activity was associated with better submaximal exercise capacity and cardiac function during the first three months of cancer therapy.

Methods: Participants included 223 women with stage I-III BC before therapy and after three months of undergoing treatment and 126 controls. Leisure time physical activity was reported using the Godin Sheppard leisure time exercise questionnaire. Cardiac function was assessed by cardiac magnetic resonance, and …

Multi-Modality Automatic Lung Tumor Segmentation Method Using Deep Learning And Radiomics, Siqiu Wang

Theses and Dissertations

Delineation of the tumor volume is the initial and fundamental step in the radiotherapy planning process. The current clinical practice of manual delineation is time-consuming and suffers from observer variability. This work seeks to develop an effective automatic framework to produce clinically usable lung tumor segmentations. First, to facilitate the development and validation of our methodology, an expansive database of planning CTs, diagnostic PETs, and manual tumor segmentations was curated, and an image registration and preprocessing pipeline was established. Then a deep learning neural network was constructed and optimized to utilize dual-modality PET and CT images for lung tumor segmentation. …

Exosomal Mirnas As Biomarkers For Radiation Toxicity In Breast Cancer Patients, Mina V. Mcginn

Theses and Dissertations

Radiotherapy (RT) is a standard treatment for most breast cancer patients (BCPs), but is often accompanied by acute and late toxic effects in normal tissue. Exosomes are nano vesicles about 30-150nm in size that originate from the endosomal network and are found in most body fluids. Exosomes are a fundamental driver of intercellular communication by transferring proteins, lipids and microRNA (miRNA). Exosomal miRNA (Exo-miRNA) signatures may serve as non-invasive prediction biomarkers of post-radiation toxicities of BCPs. Eighty six BCPs treated in the Radiation Oncology Department were enrolled in an IRB approved study. BCPs were evaluated weekly during RT and at …

Targeting Bcl-2 Family Proteins In Therapy Induced Senescent Cancer Cell Models, Wade Cook

Theses and Dissertations

Non-small Cell Lung Cancer (NSCLC) originates from numerous different cell types in the lungs and is among the deadliest of cancers. Head and Neck Squamous Cell Carcinomas (HNSCC) are derived from the mucosal membranes of the oral cavity, pharynx, and larynx. Both NSCLC and HNSCC are predominately caused by tobacco smoke inhalation and as such mutations in the tumor suppressor gene TP53 are common. Since similarities exist in the root cause of NSCLC and HNSCC, they may also share similarities in treatment methods. Cisplatin is a platinum-based DNA damaging agent that has been used as a cancer chemotherapy for decades. …

Using The Memorial Sloan Kettering Frailty Index To Identify Patients At High Risk For Postoperative Intensive Care Unit Admission, Specialized Advanced Care Unit Admission, And 30-Day Readmission, Timothy J. Donoghue

Theses and Dissertations

Frailty is roughly defined as an accumulation of physiological, emotional, cognitive, and social deficits that impair a person’s response to stressful events. A frailty diagnosis has been associated with poor outcomes following surgical procedures. Cancer surgical patients aged 65 or older represent a vulnerable population susceptible to being frail and the potential associated complications that can accompany frailty. Measuring frailty is an objective risk assessment that identifies increased risk better than age or American Society of Anesthesiologists Physical Status (ASA-PS) score such that frailty can independently predict poor surgical outcomes.

Frailty is not specifically a result of having cancer, disability, …

Strengthening Mental Health Diagnostic Detection In Integrated Primary Care, Julia Brechbiel

Theses and Dissertations

Primary care behavioral health (PCBH) is crucial for providing mental health treatment to underserved, minority, and uninsured populations. There is a lack of knowledge about accurate mental health diagnoses at PCBH. Underdetection of mental health symptoms has the potential to worsen racial and socioeconomic disparities. Using an expert review process, I developed an abbreviated diagnostic clinical interview (ADCI) for integrated primary care. Next, patients (N = 82) completed the interview after attending PCBH appointments. According to the interview, 63.4% of participants met criteria for a diagnosis, while 64.7% received a diagnosis from their provider. A large portion of patients …

A Multilevel Mixed Methods Examination Of Treatment Nonadherence Among Rural Cancer Survivors, Bonny Morris

Theses and Dissertations

While mortality rates have been decreasing over the last 40 years, cancer remains a leading cause of death in the United States. Over 1.7 million people were diagnosed with cancer in 2019, and there were more than 600,000 cancer deaths. Of the 15 million cancer survivors in the US, nearly 3 million reside in rural areas and experience 3% higher cancer incidence and 10% higher cancer mortality compared to their nonrural counterparts. During 2006-2015, the annual age-adjusted mortality rates for all cancer sites combined decreased at a slower pace in rural areas versus nonrural areas (-1.0% vs -1.6% per year, …

Sleep-Related Problems, Sleep-Related Distress, And Sleep-Related Functional Status Among Adult Inpatients Receiving Palliative Care, Lisa C. Sievers

Theses and Dissertations

Palliative care patients may be at a higher risk for sleep-related problems and their negative effects compared to the general population, yet limited sleep research has been done with this population. The purpose of this dissertation was to determine prevalence rates for excessive sleepiness, insomnia, restless legs syndrome (RLS), and high risk for sleep apnea (HRSA); examine relationships between the aforementioned sleep-related problems, sleep-related distress (SD), and sleep-related functional status (SFS); and to determine which sleep-related problem measures along with age and gender predicted SD and SFS among a sample of adult palliative care inpatients. Secondary aims were to understand …

A Deep Learning U-Net For Detecting And Segmenting Liver Tumors, Vidhya Cardozo

Theses and Dissertations

Visualization of liver tumors on simulation CT scans is challenging even with contrast-enhancement, due to the sensitivity of the contrast enhancement to the timing of the CT acquisition. Image registration to magnetic resonance imaging (MRI) can be helpful for delineation, but differences in patient position, liver shape and volume, and the lack of anatomical landmarks between the two image sets makes the task difficult. This study develops a U-Net based neural network for automated liver and tumor segmentation for purposes of radiotherapy treatment planning. Non-contrast simulation based abdominal CT axial scans of 52 patients with primary liver tumors were utilized. …

Evaluating The Clinical Utility Of A Novel Electroencephalography System For Assessing Perioperative Neurocognition In Older Surgical Patients, Lloyd H. Barnwell Iii

Theses and Dissertations

Postoperative delirium (POD) is a public health and research priority (American Society of Anesthesiologists, 2019). POD is a risk factor for long-term neurocognitive decline, and the rate of decline is directly proportional to the severity of POD (Vasunilashorn et al., 2018). Baseline cognitive function is a strong, independent predictor for POD (Culley et al., 2017). The International Perioperative Neurotoxicity Working Group recommends baseline cognitive function be assessed for older patients prior to surgery and anesthesia (Berger, et al., 2018). Perioperative cognitive screening tools trialed in anesthesia are not routinely incorporated into clinical practice related to validity, reliability, or practicality problems …

Nebulizer-Based Systems To Improve Pharmaceutical Aerosol Delivery To The Lungs, Benjamin M. Spence

Theses and Dissertations

Combining vibrating mesh nebulizers with additional new technologies leads to substantial improvements in pharmaceutical aerosol delivery to the lungs across therapeutic administration methods. In this dissertation, streamlined components, aerosol administration synchronization, and/or Excipient Enhanced Growth (EEG) technologies were utilized to develop and test several novel devices and aerosol delivery systems. The first focus of this work was to improve the poor delivery efficiency, e.g., 3.6% of nominal dose (Dugernier et al. 2017), of aerosolized medication administration to adult human subjects concurrent with high flow nasal cannula (HFNC) therapy, a form of continuous-flow non-invasive ventilation (NIV). The developed Low-Volume Mixer-Heater (LVMH) …

The Effects Of Interleukin-1Β On Cardiac Reserve And Exercise Capacity In The Mouse, Habeebah Z. Vohra

Theses and Dissertations

Heart failure (HF) is characterized by dyspnea, fatigue, and exercise intolerance. Clinical evidence points to increased interleukin-1β (IL-1β) activity in patients with HF, with an IL-1 blockade improving the exercise capacity in HF patients. In healthy mice, recombinant-mouse IL-1β (rmIL-1β) induces acute systolic dysfunction, peaking 4 hours after administration. However, the direct effects of rmIL-1β on exercise capacity are unknown. We hypothesized that rmIL-1β diminishes the exercise capacity in the mouse. Adult mice were trained to run on a treadmill and exercise capacity was assessed before, 4 hours, and 96 hours after intraperitoneal administration of rmIL-1β (3 μg/kg) or vehicle …

Investigation Of Molecular Mechanisms Of Liver Preservation Injury: A Complication Preceding Organ Transplantation, Ria C. Fyffe-Freil

Theses and Dissertations

Of the over 108,000 American awaiting a life-saving organ transplant today, over 12,000 (11%) of those need a new liver (OPTN, 2020). Last year, only 35% of patients on the waiting list for an organ were transplanted. Improving the quality of marginal organs by preventing or reversing preservation injury could vastly increase the number of transplants performed. Washout of circulating blood during liver procurement with cold University of Wisconsin solution flushes out any endogenous pro-survival signaling molecules. We investigated lysophospholipid (LPL) surface receptors (G-protein coupled receptors for lysophosphatidic acid (LPA) and sphingosine- 1-phosphate (S1P)) and their role in protecting hepatocytes …

Development Of A Torque-Based Device For The Quantification Of Arm Rigidity In Patients With Parkinson’S Disease, Georgina O. Miller

Theses and Dissertations

Parkinsonian rigidity is caused by the inability of the muscles to relax and extend properly, due to reduced dopamine levels and often begins on one side of the body before spreading contralaterally. The current standard for determining joint rigidity in a clinical setting is a test completed by the clinician based on the feel of the relaxed wrist and elbow joints as they are passively flexed and extended and a series of ordinal rating scales, the Movement Disorder Society’s – Unified Parkinson’s Disease Rating Scale (MDS-UPDRS), Hoehn and Yahr Scale (H&Y), and Parkinson’s Disease Questionnaire-39 (PDQ-39). These methods are used …

Process Factors Affecting Reperfusion Time In Patients Presenting With St-Segment Elevation Myocardial Infarction (Stemi), Richard R. Wall

Theses and Dissertations

Abstract PROCESS FACTORS AFFECTING REPERFUSION TIME IN PATIENTS

PRESENTING WITH ST-SEGMENT ELEVATION MYOCARDIAL INFARCTION (STEMI) By Richard R. Wall MSRS, RT(R)(CT)(CI), RCIS

A dissertation submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy at Virginia Commonwealth University.

Virginia Commonwealth University, 2020.

Dissertation Chair: Jeffrey S. Legg Ph.D. Associate Professor and Chair, Department of Radiation Sciences

An ST-segment myocardial infarction (STEMI) occurs when the blood flow to the myocardium is suddenly and completely blocked causing the myocardium to become ischemic. A STEMI is a life-threatening condition that necessitates emergent medical treatment. Research has shown that longer …