Theses and Dissertations from UMD
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New submissions to the thesis/dissertation collections are added automatically as they are received from the Graduate School. Currently, the Graduate School deposits all theses and dissertations from a given semester after the official graduation date. This means that there may be up to a 4 month delay in the appearance of a give thesis/dissertation in DRUM
More information is available at Theses and Dissertations at University of Maryland Libraries.
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Item Deployment of Large Vision and Language Models for Real-Time Robotic Triage in a Mass Casualty Incident(2024) Mangel, Alexandra Paige; Paley, Derek; Aerospace Engineering; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)In the event of a mass casualty incident, such as a natural disaster or war zone, having a system of triage in place that is efficient and accurate is critical for life-saving intervention, but medical personnel and resources are often strained and struggle to provide immediate care to those in need. This thesis proposes a system of autonomous air and ground vehicles equipped with stand-off sensing equipment designed to detect and localize casualties and assess them for critical injury patterns. The goal is to assist emergency medical technicians in identifying those in need of primary care by using generative AI models to analyze casualty images and communicate with the victims. Large language models are explored for the purpose of developing a chatbot that can ask a casualty where they are experiencing pain and make an informed assessment about injury classifications, and a vision language model is prompt engineered to assess a casualty image to produce a report on designated injury classifiers.Item PREPARATION OF A NANOSUSPENSION OF THE PHOTOSENSITIZER VERTEPORFIN FOR PHOTODYNAMIC AND LIGHT-INDEPENDENT THERAPY IN GLIOBLASTOMA(2024) Quinlan, John Andrew; Huang, Huang-Chiao; Bioengineering; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Photodynamic therapy (PDT) using verteporfin (VP) has treated ocular disease for over 20 years, but recent interest in VP’s light-independent properties has reignited interest in the drug, particularly in glioblastoma (GBM) (NCT04590664). Separate efforts to apply PDT to GBM using 5-aminolevulinic acid (5-ALA)-induced protoporphyrin IX (PpIX) have also garnered attention (NCT03048240), but, unfortunately, clinical trials using 5-ALA-induced PpIX-PDT have yet to yield a survival benefit. Previous studies have shown VP to be a superior PDT agent than 5-ALA-induced PpIX. Our lab has shown that 690 nm light activates VP up to 2 cm into the brain, while 635 nm light only activates PpIX at depths <1 cm into the brain. Additionally, VP is a more effective photosensitizer than PpIX because it has a higher singlet oxygen yield and is active in the vasculature as well as target tumor cells. However, the hydrophobicity of VP limits effective delivery of the drug to the brain for treatment of GBM.In this context, this thesis aims to re-evaluate the delivery method for VP. VP traditionally requires lipids for delivery as Visudyne. Recent shortages of Visudyne and potential drawbacks of liposomal carriers motivated our development of a carrier-free nanosuspension of VP, termed NanoVP. Previous work has shown that cellular uptake of VP is greater when delivered as NanoVP rather than liposomal VP, resulting in improved cell killing after light activation. This thesis builds on this previous work by (1) evaluating synthesis and storage parameters for NanoVP, (2) determining the pharmacokinetics, biodistribution, and brain bioavailability of NanoVP, and (3) evaluating the potential efficacy of NanoVP as a PDT and a chemotherapy agent, and by supporting development of a zebrafish model of the blood-brain barrier (BBB) for mechanistic studies of improved drug delivery to the brain.Item Value sets for the analysis of real-world patient data: Problems, theory, and solutions(2024) Gold, Sigfried; Lutters, Wayne; Information Studies; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Observational, retrospective, in silico studies based on real-world data—that is, data for research collected from sources other than randomized clinical trials—cost a minute fraction of randomized clinical trials and are essential for clinical research, pharmacoepidemiology, clinical quality measurement, health system administration, value-based care, clinical guideline compliance, and public health surveillance. They offer an alternative when randomized trials cannot provide large enough patient cohorts or patients representative of real populations in terms of comorbidities, age range, disease severity, rare conditions.Improvements in the speed, frequency, and quality of research investigations using real-world data have accelerated with the emergence of distributed research networks based on common data models over the past ten years. Analyses of repositories of coded patient data involve data models, controlled medical vocabularies and ontologies, analytic protocols, implementations of query logic, value sets of vocabulary terms, and software platforms for developing and using these. These studies generally rely on clinical data represented using controlled medical vocabularies and ontologies—like ICD10, SNOMED, RxNorm, CPT, and LOINC—which catalogue and organize clinical phenomena such as conditions, treatments, and observations. Clinicians, researchers, and other medical staff collect patient data into electronic health records, registries, and claims databases with each phenomenon represented by a code, a concept identifier, from a medical vocabulary. Value sets are groupings of these identifiers that facilitate data collection, representation, harmonization, and analysis. Although medical vocabularies use hierarchical classification and other data structures to represent phenomena at different levels of granularity, value sets are needed for concepts that cover a number of codes. These lists of codes representing medical terms are a common feature of the cohort, phenotype, or other variable definitions that are used to specify patients with particular clinical conditions in analytic algorithms. Developing and validating original value sets is difficult to do well; it is a relatively small but ubiquitous part of real-world data analysis, it is time-consuming, and it requires a range of clinical, terminological, and informatics expertise. When a value set fails to match all the appropriate records or matches records that do not indicate the phenomenon of interest, study results are compromised. An inaccurate value set can lead to completely wrong study results. When value set inaccuracy causes more subtle errors in study results, conclusions may be incorrect without catching researchers’ attention. One hopes in this case that the researchers will notice a problem and track it down to a value set issue. Verifying or measuring value set accuracy is difficult and costly, often impractical, sometimes impossible. Literature recognizing the deleterious effects of value set quality on the reliability of observational research results frequently recommends public repositories where high-quality value sets for reuse can be stored, maintained, and refined by successive users. Though such repositories have been available for years and populated with hundreds or thousands of value sets, regular reuse has not been demonstrated. Value set quality has continued to be questioned in the literature, but the value of reuse has continued to be recommended and generally accepted at face value. The hope for value set repositories has been not only for researchers to have access to expertly designed value sets but for incremental refinement, that, over time, researchers will take advantage of others’ work, building on it where possible instead of repeating it, evaluating the accuracy of the value sets, and contributing their changes back to the repository. Rather than incremental improvement or indications of value sets being vetted and validated, what we see in repositories is proliferation and clutter: new value sets that may or may not have been vetted in any way and junk concept sets, created for some reason but never finished. We have found general agreement in our data that the presence of many alternative value sets for a given condition often leads value set developers to ignore all of them and start from scratch, as there is generally no easy way to tell which will be more appropriate for the researcher’s needs. And if they share their value set back to the repository, they further compound the problem, especially if they neglect to document the new value set's intention and provenance. The research offered here casts doubt on the value of reuse with currently available software and infrastructure for value set management. It is about understanding the challenges value sets present; understanding how they are made, used, and reused; and offering practice and software design recommendations to advance the ability of researchers to efficiently make or find accurate value sets for their studies, leveraging and adding to prior value set development efforts. This required field work, and, with my advisors, I conducted a qualitative study of professionals in the field: an observational user study with the aim of understanding and characterizing normative and real-world practices in value set construction and validation, with a particular focus on how researchers use the knowledge embedded in medical terminologies and ontologies to inform that work. I collected data through an online survey of RWD analysts and researchers interviews with a subset of survey participants, and observation of certain participants performing actual work to create value sets. We performed open coding and thematic analysis on interview and observation transcripts, interview notes, and open-ended question text from the surveys. The requirements, recommendations, and theoretical contributions in prior literature have not been sufficient to guide the design of software that could make effective leveraging of shared value sets a reality. This dissertation presents a conceptual framework, real-world experience, and deep, detailed account of the challenges to reuse, and makes up that deficit with a high-level requirements roadmap for improved value set creation tools. I argue, based on the evidence marshalled throughout, that there is one way to get researchers to reuse appropriate value sets or to follow best practices in determining whether a new one is absolutely needed creating their own and dedicate sufficient and appropriate effort to create them well and prepare them for reuse by others. That is, giving them software that pushes them to do these things, mostly by making it easy and obviously beneficial to do them. I offer a start in building such software with Value Set Hub, a platform for browsing, comparing, analyzing, and authoring value sets—a tool in which the presence of multiple, sometimes redundant, value sets for the same condition strengthens rather than stymies efforts to build on the work of prior value set developers. Particular innovations include the presentation of multiple value sets on the same screen for easy comparison, the display of compared value sets in the context of vocabulary hierarchies, the integration of these analytic features and value set authoring, and value set browsing features that encourage users to review existing value sets that may be relevant to their needs. Fitness-for-use is identified as the central challenge for value set developers and the strategies for addressing this challenge are categorized into two approaches: value-set-focused and code-focused. The concluding recommendations offer a roadmap for future work in building the next generation of value set repository platforms and authoring tools.Item Attachment and Pain Catastrophizing From a Communal Coping Perspective in Women With Chronic Pain(2021) Reeves, Elizabeth; Hoffman, Mary Ann; Counseling and Personnel Services; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Chronic pain is a devastating public health problem particularly in women, who are at increased risk for chronic conditions and report more depression and disability secondary to pain relative to men. The impact of relationships, which are critical to the experience and management of pain as well as central to the female gender role, may help to explain gender disparities. The present study uses the Communal Coping Model of Pain Catastrophizing (CCM) and the Attachment-Diathesis Model of Chronic Pain (ADMoCP) to investigate how relationship patterns influence coping responses in women with chronic pain. It seeks to clarify the mechanisms by which unmet attachment needs contribute to pain catastrophizing and influence perceptions of others’ responses to pain and pain-related behaviors. Furthermore, it seeks to examine how insecure attachment might contribute to lower levels of adaptive, intrapersonal responses to pain such as self-compassion, and whether addressing these deficits might represent a viable target for intervention. A total of 355 women with generalized chronic pain conditions (Fibromyalgia, Rheumatoid Arthritis, and/or Myofascial Pain Syndrome) completed an online survey. Exploratory analyses examine relationships between attachment, pain appraisals, pain catastrophizing, self-compassion, depression, and disability. Additional analyses test the CCM and the ADMoCP by investigating: (1) two possible mechanisms by which attachment needs might influence pain catastrophizing, depression, and disability; and (2) the role of attachment and pain catastrophizing in shaping perceptions of others’ responses to pain and pain-related behaviors. Findings have implications for conceptualization and treatment from an attachment perspective.Item Formulation and Delivery of Enhanced Extracellular Vesicles for Wound Repair(2021) Born, Louis Joseph; Jay, Steven M; Bioengineering; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Despite the development of a variety of therapies, complex wounds resulting from disease, surgical intervention, or trauma remain a major source of morbidity. Extracellular vesicles (EVs) have recently emerged as an alternative approach to address this issue. In particular, EVs derived from mesenchymal stem/stromal cells (MSCs) have been shown to improve wound healing, especially via enhanced wound angiogenesis. However, despite their clearly established potential, EVs have limitations that limit clinical relevancy, including low potency and rapid clearance from the body. Additionally, the ability to sustainably deliver EVs may enhance their efficacy in wound healing. Here, we leveraged the capability of EVs to be engineered via producer cell modification to investigate the therapeutic potential of EVs from MSCs transfected to overexpress a well-established pro-angiogenic long non-coding RNA HOX transcript antisense RNA (HOTAIR). We established that HOTAIR was able to be successfully loaded into MSC EVs (HOTAIR-MSC EVs) and delivered to endothelial cells in vitro with increased functional angiogenic activity. HOTAIR-MSC EVs injected intradermally around excisional wounds also showed increased angiogenic activity in vivo in two different species of rodents and improved wound healing in diabetic mice. We further report biomaterial-enabled sustained release of EVs using injectable hydrogel nanoparticles containing a composite of thiolated hyaluronic acid, maleimide functionalized poly(ε-caprolactone), and polyethylene glycol tetraacryalte as well as 3D-printed hydrogel discs composed of gelatin methacrylate for topical application. EVs released from the formulation of both of these biomaterials retained angiogenic bioactivity. Nanoparticles containing HOTAIR-MSC EVs were injected intradermally around an excisional wound in diabetic mice and were able to increase angiogenesis and improve wound healing. EVs released from 3D-printed EV-loaded GelMa hydrogels retained bioactivity in an in vitro endothelial scratch assay. Overall, these data suggest increasing the content of lncRNA HOTAIR in MSC EVs as a promising wound healing therapeutic. Additionally, establishing a biomaterial-enabled sustained release therapeutic represents a promising translational product for clinical implementation.Item Troublesome Properties: Race, Disability, and Slavery's Haunting of the Still Image(2019) Mobley, Izetta Autumn; Corbin Sies, Mary; American Studies; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Troublesome Properties: Race, Disability, and Slavery’s Haunting of the Still Image interrogates race, disability, slavery, and the visual, arguing for a reorientation of disability studies toward a comprehensive analysis of how Atlantic slavery structured the West’s conceptualization of the abled body. Slavery haunts the aesthetic impulses, discursive engagements, and visual formations that construct both disability and race. Slavery and disability have been historically mutually constitutive, establishing a network of power relations that define how the United States understands citizenship, sovereignty of the body, capital, labor, and bodily integrity. Troublesome Properties’ intervention places photography – specifically nineteenth-century daguerreotypes, cartes de visites, and portraiture –in conversation with race, disability and slavery, inviting a critical look at the social resonance of photographic production. This interdisciplinary project is deeply invested in the nineteenth century and critically considers how visual imagery establishes concepts of disabled and abled bodies. The visual and material analysis of visual culture and photography links my discussion of disability to racially marked bodies, explicitly illustrating how slavery haunts how we see and tie Blackness to disability. The illustrations, photographs, medical records, biographies, and ephemera of conjoined African American twins Millie and Christine McKoy serve as evidence of the troubled definitions of consent, care, property, and exploitation inherent in enslavement, disability, and display. Octavia Butler’s 1979 speculative novel, Kindred, anchors my discussion of the impact of disability on Black disabled women. Black scholars, artists, and historians have consistently employed photography as a visual tool to assert the humanity of Black people. The photographic suite Dorian Gray by Yinka Shonibare, a series that makes overt the parallels between disability and colonialism, are placed in conversation with W.E. B. Du Bois’ American Negro exhibit, demonstrating how race, disability, and the visual construct notions of which bodies matter, when, where, and why. In Troublesome Properties, I argue that we must approach visual production, material culture, and disability studies with the intention to reclaim the marked, raced, gendered, and disabled Black body, using slavery and an optimistic pessimism to construct a complex genealogy for disability studies.Item INVESTIGATION OF DEFECTIVE CELL SIGNALING CASCADE INVOLVED IN THE OSTEOGENESIS IN HUTCHINSON-GILFORD PROGERIA SYNDROME(2018) Choi, Ji Young; Cao, Kan; Cell Biology & Molecular Genetics; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Human bone homeostasis is maintained through constant bone remodeling, which balances bone formation by osteoblasts and bone resorption by osteoclasts. Patients with Hutchinson-Gilford progeria syndrome (HGPS) have low bone mass that manifests in a high risk of fractures and an atypical skeletal geometry, suggesting impaired bone remodeling. HGPS is a premature aging disease caused by truncated lamin A that is permanently farnesylated. The mutant lamin A is referred as progerin. Several previous clinical reports discussed abnormal skeletal development of the children with HGPS, but the molecular mechanistic study on defective osteogenesis of HGPS stem cells need to be further elucidated. The major aim of my dissertation research is to investigate dysfunction in stem cell differentiation due to aberrant cell signaling in osteoprogenitor cells that express progerin. To achieve this aim, the study demonstrates both in vitro and in vivo models of HGPS to support defective mechanism of the canonical WNT/β-catenin pathway, seemingly at the level of efficiency of nuclear import of β-catenin and impaired osteoblast differentiation. Restoring β-catenin activity rescues osteoblast differentiation and significantly improves bone mass. In particular, HGPS patient-derived induced pluripotent stem cells (iPSCs)-osteoprogenitors and primary mesenchymal stem cells (MSCs) expressing the HGPS mutant progerin display defects in osteoblast differentiation, characterized by deficits in alkaline phosphatase activity and mineralizing capacity. Mechanistic investigation reveals that canonical WNT/β-catenin pathway, a major signaling cascade involved in skeletal homeostasis, is impaired by progerin, causing a reduction in nuclear active β-catenin protein levels and reciprocal aberrant cytoplasmic accumulation which causes reduced transcriptional activity for osteogenesis. Non-farnesylation of progerin in MSCs attains higher level of active β-catenin protein expression and consequently increasing the signaling, enhancing mineralization capacity and ameliorating the defective osteogenesis. Moreover, in vivo analysis of the Zmpste24-/- HGPS mouse model demonstrates that treatment with a sclerostin-neutralizing antibody (SclAb), which targets an antagonist of canonical WNT/β-catenin signaling pathway, fully rescues the low bone mass phenotype to wild-type levels. This study implicates β-catenin signaling cascade as a therapeutic target for restoring defective skeletal microarchitecture in HGPS. Given the fundamental nature of WNT/β-catenin signaling to stem cell renewal and lineage allocation, the findings from this dissertation may provide broader inferences for the treatment options in HGPS.Item Linguistic Orphan: Medical Literacy in Medieval England and the Erasure Of Anglo-Saxon Medical Knowledge(2018) Willis, Margot Rochelle; Bianchini, Janna; History; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)This thesis seeks to answer the question of why medieval physicians “forgot” efficacious medical treatments developed by the Anglo-Saxons and how Anglo-Saxon medical texts fell into obscurity. This thesis is largely based on the 2015 study of Freya Harrison et al., which replicated a tenth-century Anglo-Saxon eyesalve and found that it produced antistaphylococcal activity similar to that of modern antibiotics. Following an examination of the historiography, primary texts, and historical context, this thesis concludes that Anglo-Saxon medical texts, regardless of what useful remedies they contained, were forgotten primarily due to reasons of language: the obsolescence of Old English following the Norman Conquest, and the dominance of Latin in the University-based medical schools in medieval Europe.Item Couples Coping with Li-Fraumeni Syndrome: A Mixed-Methods Study of Family Strengths(2018) Young, Jennnifer Louise; Epstein, Norman B; Family Studies; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Using mixed methodology involving qualitative and quantitative data, this dissertation fills gaps in knowledge regarding psychosocial implications for families living with the genetically-transmitted Li-Fraumeni cancer susceptibility syndrome, specifically targeting couple dyads. An initial review of the existing literature on couples coping with heritable cancer syndromes identified gaps in knowledge, and pointed to future directions for research in this area. The three papers that comprise this dissertation provide multiple perspectives on the levels of distress, coping styles, and social support patterns of couples in which one partner is at high risk of cancer. The first paper investigates spousal distress and coping styles in relation to cancer worry for individuals with Li-Fraumeni Syndrome, using quantitative data from one of the largest existing collections of Li-Fraumeni Syndrome cases. The second paper identifies couples’ coping and communication processes regarding cancer stressors, using semi-structured qualitative interviews of individuals with Li-Fraumeni Syndrome and their partners. The third paper utilizes a social network approach to illustrate shared patterns of emotional, tangible, and informational support that couples report accessing. The integrated findings from these three studies indicate that these subjects are low in general distress but high in cancer-specific worry. Couples cope with this worry by balancing multiple roles, exercising flexibility in family dynamics, and utilizing extensive social support networks. This research provides significant information that can aid in development of effective interventions for couples as they face their ongoing threat of cancer. Recommendations for clinical work with this population include an integrated blend of couple therapy, genetic counseling, and oncology practice that is sensitive to the unique needs of individuals with heritable cancer syndromes and their partners.Item THE USE OF ACTIGRAPHY FOR RISK STRATIFICATION IN PEDIATRIC OBSTRUCTIVE SLEEP APNEA(2018) Bertoni, Dylan Gregory; Isaiah, Amal; Bioengineering; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Objectives. (i) To determine the feasibility of using actigraphy to identify sleep interruption in children with suspected obstructive sleep apnea (OSA); (ii) to assess the utility of actigraphy for prediction of OSA severity. Subjects and Methods. Ten healthy children aged 2 to 15 years with suspicion for OSA underwent polysomnography (PSG) with actigraphy. Statistical learning algorithms were used to (i) identify sleep-related respiratory events (awake, asleep, hypopneas and apneas), and (ii) predict OSA severity (mild, moderate and severe) utilizing actigraphy counts. Results. No adverse events were identified. Actigraphy counts were obtained in all 10 children. Linear discriminant analysis identified 100% of patients with severe OSA. Actigraphy counts reliably identified hypopneas and awakenings but not apneas. Conclusions. Actigraphy counts may provide effective risk stratification for pediatric OSA. Further investigations are necessary to investigate the utility of using actigraphy and pulse oximetry together to identify all respiratory events during sleep.
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