Theses and Dissertations from UMD
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Item ALLOSTATIC LOAD INFLUENCES VASCULAR FUNCTION AND SYMPATHOLYSIS IN YOUNG BLACK ADULTS(2024) Eagan, Lauren Elizabeth; Ranadive, Sushant M; Kinesiology; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)In the U.S., Black individuals tend to face a disproportionately higher risk for hypertension. This is largely attributed to chronic sympathetic activation induced by heightened exposure to psychosocial stressors. Allostatic load (AL), an index of cumulative physiological dysfunction from chronic stress, is associated with hypertensive risk and is also heightened in Black adults compared to those of other racial groups. Indeed, increased sympathetic activity is a hallmark characteristic of both hypertension and AL. The inability to blunt sympathetic-induced vasoconstriction during exercise (impaired functional sympatholysis) is also associated with hypertension. This dissertation aimed to investigate whether AL was associated with measures of vascular health in young Black adults, both at rest and during a sympathetic stressor. In our first study, we examined associations between AL and indices of vascular function and structure among young Black adults at rest, finding that higher AL was associated with greater macrovascular dysfunction and amplified wave-reflections. Additionally, we identified significant correlations among greater self-perceived stress with smaller brachial artery diameters and greater wave-reflections. The second aim of this dissertation focused on the associations between AL and the magnitude of functional sympatholysis among this population. Results indicated a positive association between AL and functional sympatholysis, with amplified sympatholytic responses among young Black females, as compared to their male counterparts, when forearm volume was controlled for. Overall, our findings suggest that elevated AL might predict macrovascular dysfunction at rest, with larger arterial diameters potentially compensating for chronic stress. These adaptive mechanisms, commonly observed in aging and diseased states, may also explain the positive correlations between AL and the functional sympatholytic response in young Black adults. Our consistent observations of the redundant vascular mechanisms among young Black adults allowing for adaptation to chronic stress strengthen our findings and further highlight the complex interplay between stress and cardiovascular health in Black adults.Item LGBTQ+ Youth Therapeutic Engagement and Experiences: Associations with LGBTQ+ Family Environment(2024) Zheng, Azure; Fish, Jessica N,; Family Studies; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)LGBTQ+ youth experience unique stressors that increase the risk for poor mental health. LGBTQ+ youth’s family environment, often measured as parental acceptance and rejection of youth’s LGBTQ+ status, is associated with youth mental health; less often studied is how the family environment may be linked to LGBTQ+ youth’s access to therapy and, more importantly, experiences with LGBTQ+ affirmative and competent providers. Using a contemporary non-probability national sample of LGBTQ+ youth ages 13-17, our study examined the association among LGBTQ+ youth’s reports of caregiver supportive and rejection behaviors related to their LGBTQ+ identity and youth’s engagement and experiences in therapy. Using a step-wise logistic regression method, results tell a clear story. There is a consistent positive association between parent’s LGBTQ+ support behaviors and (1) youth access to therapy and (2) their therapists' LGBTQ+ competency. In the absence of controls, we found that parents’ rejecting behaviors were also positively associated with the youth’s access to therapy, but this relationship was mediated by the youth’s depression and anxiety symptoms. For youth who did not access therapy in the last year, those who reported more parental support were inversely related, and parental rejection positively related to wanting therapy but not receiving it. Youth who reported more rejecting behaviors from parents were less likely to perceive their therapists as LGBTQ+ competent. Findings point to varied pathways and experiences in therapy engagement for LGBTQ+ youth based on parents' support of their LGBTQ+ identity.Item LOWER LIMB ASYMMETRY AND LOADING IN INDIVIDUALS WITH UNILATERAL TRANSFEMORAL AMPUTATIONS WITH A LIFETIME OF OSSEOINTEGRATED PROSTHESIS USE(2023) Burnett, Jenna K; Shim, Jae Kun; Kinesiology; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Individuals with transfemoral amputation commonly develop chronic health problems due to decreased physical activity as a result of the missing musculature and tissue on the amputated side, and the poor imitation of the intact limb provided by the prosthesis. In addition, the indirect and semi-rigid connection of the socket to the body may increase interlimb asymmetries, as well as lead to pain and discomfort on the residual limb. Recent innovations have introduced a bone-anchored or osseointegrated (OI) implant which connects the prosthesis to the skeleton, and removes most of the socket related pain and discomfort complaints, as well as providing a rigid connection which may reduce the interlimb asymmetries. However, the direct bone and prosthesis connection may also introduce longitudinal bone health concerns due to the repetitive loads during walking. This dissertation investigated the effect of walking speed on the loads placed on the lower limbs of 11 individuals who use an OI prosthesis at 3 different anatomical levels, including the whole limb through interlimb ground reaction force, the joints through interlimb joint kinematics and kinetics, and finally the residual limb bone through implant input forces, finite element analysis of bone strain, and the probability of bone injury with a simulated lifetime of use.In study 1, the interlimb ground reaction force asymmetries were found to be moderate to large at all walking speeds, and to have a general increase as individuals walked faster, indicating there is an intact limb reliance strategy which may be used to compensate for the limitations of the amputated limb. Similarly, in study 2, the interlimb joint kinematics and kinetics were found to have moderate to large asymmetries at each joint level, with a general increase in asymmetry at faster walking, with this increase largely due to limitations within the prothesis. In study 3, the abutment force decreased in magnitude with walking speed, but the peak strain on the bone, and the probability of injury was greater for the preferred speed and fast speed walking when compared to slow speed walking. However, the overall probability of injury was low for all speeds, indicating the ability of the bone to repair and adapt with sustained loading likely provides effective protection over a lifetime of simulated OI prothesis use. The findings of this dissertation suggest that the more rigid connection afforded by the OI implant cannot fully remove the interlimb asymmetries which occur as a result of the poor imitation of the intact limb provided by the prosthesis and prosthesis components, but that there is minimal risk to the bone due to a lifetime of sustained walking with an OI prosthesis as a result the inherent ability of the bone to repair and adapt to variable loads over time. Therefore, while an OI prosthesis may not fully mitigate the interlimb asymmetries which occur as a result of the prosthesis limitations, individuals who use an OI prosthesis may feel confident that there is minimal longitudinal risk to the bone as a result of walking over their lifetime.Item Home Hemodialysis Utilization and Health Outcomes among Racial and Ethnic Minority Populations(2023) Zhu, Ying; Franzini, Luisa; Health Services Administration; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Background: Home hemodialysis (HHD) offers end-stage renal disease (ESRD) patients greater flexibility and advantages in terms of health outcomes over in-center hemodialysis. There is limited research on the differences between home and center hemodialysis (CHD) and preferences among racial/ethnic minorities, despite ESRD disproportionately affecting these groups. Methods: This project aims to explore the usage and health outcomes of HHD vs. CHD with a focus on racial/ethnic differences using a systematic review of the global main academic database from 2004 to 2022 (study 1), logistic regression and negative binomial analysis of the U.S. Renal Disease System (USRDS) cumulative core data since 2010 merged with 2016-2019 Medicare clinical claims (study 2), and qualitative research using semi-structured interviews with 18 nephrologists and 5 other hemodialysis providers in 8 states of the U.S. (study 3). Results: Study 1: from 3,114 unique studies, six studies met the inclusion criteria and all of them were comparative cohort studies; five out of six studies with a total of 3,172 White patients (68%) and 1,477 minority patients (32%) reported the utilization of HHD; in four of the six studies, the adjusted odds ratio for HHD treatment was shown to be significantly lower for patients of racial or ethnic minorities than for White patients; three out of six studies examined racial/ethnic differences in mortality and other outcomes indicating a lower risk of death for minorities in home hemodialysis. Study 2: minorities were significantly less likely to use HHD than Whites; most minority patients were younger and had fewer comorbidities than Whites, and all minority groups displayed significantly lower mortality and hospitalization incidences than the White group with adjustment on multiple covariates; in the overall and main racial/ethnic cohorts, HHD showed a significantly lower risk of death than CHD after confounding for major risk factors. Study 3: the majority of the interviewees felt that HHD was a viable, safe, and most cost-effective treatment for those with kidney failure, it offered many advantages over traditional CHD but there is a need for additional training and support for the patient, family, provider; minorities and White patients differed in their attitude toward dialysis care, social norms on HHD, and perceived control of personal health. Conclusion: There were major obstacles and considerable racial/ethnic variations in HHD utilization and health outcomes in the US. This study showed that the promotion of HHD will probably require a systematic overhaul in kidney disease management and education.Item Show and Tell: Exploring how audio narratives can complement visualizations of stroke survivors’ personal health data(2023) Shettigar, Aishwarya; Choe, Eun Kyoung; Library & Information Services; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Wearable technology in healthcare could give individuals awareness and independence in rehabilitation. In this qualitative work, I investigate how using speech-based, audio narrative summaries alongside graphical visualizations affect users’ understanding of their personal data. I conducted this work in the context of stroke recovery, where stroke survivors experiencing hemiparesis can monitor their physical progress using a wearable ring sensor. Using a co-design approach, I engaged with stroke survivors and their caregivers to elicit recommendations for multimodal (speech/visual) feedback of the wearable ring data. Reflexive thematic analysis of the sessions showed that multimodal feedback can potentially lend therapeutic support for stroke survivors. Audio narratives helped to reinforce the visual feedback, and positively framed narrative content that was reflective, motivational, and suggestive was able to support stroke survivors as they navigate their independent recovery journeys.Item Development and characterization of Epstein-Barr virus (EBV) antibodies and testing their efficacy in a humanized mouse model(2022) Kim, JungHyun Rachel; Zhu, Xiaoping; Biology; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Epstein-Barr virus (EBV) is one of the most prevalent human viruses with more than 90% of the adult population infected with EBV. EBV is well-known to cause infectious mononucleosis, but also is associated with several B cell lymphomas and epithelial cell carcinomas. In bone marrow or solid organ transplant patients and individuals with X-linked lymphoproliferative disease, primary EBV infection can lead to life-threatening complications. There is no licensed vaccine and even if one is available, these immunocompromised individuals might not respond well to the vaccine. Thus, an effective vaccine and therapeutic are both needed. Here, I have evaluated the efficacy of (a) EBV hyperimmune globulin isolated from healthy plasma donors with high EBV gp350 antibody and EBV B cell neutralizing titers, (b) several EBV gp350, gH/gL and gp42 monoclonal antibodies (mAbs) isolated from human plasma or vaccinated monkeys, (c) a bispecific antibody targeting both gH/gL and gp42, and (d) gH/gL and gH/gL/gp42 nanoparticle vaccines in a humanized mouse model. Animals that received hyperimmune globulin showed protection from EBV infection at a similar level as that seen in animals receiving intravenous immunoglobulin. However, humanized mice that received gH/gL mAb B10 or gp42 mAb A10 showed increased survival and reduced viremia compared to animals that received other gH/gL or gp42 mAbs. These two mAbs also demonstrated protection from development of EBV B cell lymphomas in animals. Humanized mice that received bispecific antibody derived from gH/gL mAb B10 and gp42 mAb A10 showed similar protection against EBV as animals that received the combination of the two antibodies. Passive transfer of IgG isolated from mice immunized with a gH/gL or gH/gL/gp42 nanoparticle vaccine showed reduction in viremia and no development of EBV lymphomas compared to mice that received IgG from naïve mice. These findings suggest that development of vaccines or therapeutics targeting gH/gL and/or gp42 may provide protection in healthy individuals and severely immunocompromised individuals from EBV infection and B cell lymphoma.Item A Qualitative Examination of the Barriers and Facilitators of Pre-Exposure Prophylaxis (PrEP) Uptake Among Heterosexual HIV Serodiscordant Couples(2022) Mathews, Ronneal; Mittal, Mona; Family Studies; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)It is estimated that there are 140,000 heterosexual serodiscordant couples in the United States. Given the considerable number of these couples and the high risk of HIV acquisition among non-infected partners, it is important to focus prevention methods on programs and interventions that target transmission of HIV infection among serodiscordant heterosexual couples. Currently, we understand little about factors that influence these couples to use pre-exposure prophylaxis (PrEP). According to the CDC, this population is one of the highest risk groups, therefore, understanding the factors that influence them to use PrEP as a strategy in their HIV prevention regimen is an important step in preventing new HIV cases among this population. This study was a qualitative analysis that explored potential motivators and inhibitors for PrEP among heterosexual HIV serodiscordant couples. Secondary data from 26 qualitative interviews of HIV serodiscordant couples (N = 52 individuals) was examined to determine the factors that influenced the decision to use PrEP. Overall, there were five overarching themes from the Health Belief Model that manifested in all participant interviews. Perceived threat, perceived barriers (concerns about side effects, fear/anxiety about taking medication, indifference about HIV transmission), perceived benefits, cues to action (partner protection, PrEP use as condom replacement, PrEP use due to concerns about condom efficacy), and relational efficacy emerged as the most salient themes that determined whether couples chose to use PrEP as an HIV prevention method. Two constructs from the Theory of Gender and Power, sexual division of power and cathexis also emerged as relevant factors that influenced the decision to use PrEP in these couples. Findings from this study indicate that practitioners need to consider the motivators and barriers to PrEP uptake, and critically examine how power dynamics impact the decision to use PrEP. There is a need for the development of couples-based interventions to encourage PrEP uptake and adherence in mixed status couples.Item Regulation of Mitochondrial Metabolism and Lipogenesis(2021) Surugihalli, Chaitra; Sunny, Nishanth E; Animal Sciences; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Non-alcoholic fatty liver disease is one of the most common liver disorders with a global prevalence of over 25%. Fatty liver is the most common comorbidity of insulin resistance, obesity, and type 2 diabetes mellitus. During fatty liver, nutrient overload and the associated hyperinsulinemia results in elevated circulating free fatty acids and lipid accumulation in the liver. High rates of lipid accumulation in the liver is partly attributed to high rates of lipogenesis from carbohydrates, together with dysfunctional lipid oxidation. Further, these dysfunctional metabolic networks will induce oxidative stress and inflammation. Thus, understanding the metabolic mechanisms contributing towards the etiology of fatty liver and its associated morbidities is of major interest towards developing prevention and management strategies. This dissertation utilizes a combination of in-vivo (chicken and mice) and in-vitro (isolated mitochondria) systems with stable isotope-based methodologies to study metabolic regulation.Chicken embryos utilize yolk lipids (>45%), deriving over 90% of their energy through lipid oxidation for development. However, during the last few days of incubation and immediately after hatch, there is a substantial induction of lipogenesis. Despite the hepatic lipid overload, the synergistic remodeling of hepatic metabolic networks during embryonic-to-neonatal development blunted inflammatory onset, prevented accumulation of lipotoxic intermediates, and reduced reactive oxygen species production. Elevated plasma branched-chain amino acids (BCAAs) are a characteristic of insulin resistance and are relevant in predicting T2DM. Defects in BCAA degradation networks are also evident in several tissues during insulin resistance and associated co-morbidities. Furthermore, alterations in BCAA metabolism are associated with changes in lipogenesis and mitochondrial oxidative networks. We utilize a combination of isolated mitochondrial systems and stable isotope tracers in diet-induced mouse models of fatty liver, to determine its impact on mitochondrial metabolism and lipogenesis. In summary, the dissertation highlights i) the importance of the natural but dynamic remodeling of hepatic mitochondrial metabolism and lipogenesis during the efficient embryonic-to-neonatal transition in chicken ii) the significance of BCAAs as important regulators of hepatic mitochondrial lipid metabolism. Thus, these studies provide a platform to modulate hepatic metabolic networks and utilize the embryonic-to-neonatal transition phase and dietary intervention of BCAAs as management strategies to alleviate metabolic dysfunctions.Item A DISCOURSE ON CHILD MALNUTRITION: ANTHROPOMETRY, EMERGENT THEMES, QUALITY CONTROL MAXIMS, AND CLIMATIC AND ECONOMIC DETERMINANTS(2021) Sandler, Austin; Sun, Laixiang; Geography; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Malnutrition is a detrimental and significant plight for young children, responsible for 45% of all deaths among children worldwide. The aim of my dissertation is to assess the history of the science of anthropometry, synthesize the cumulative findings within the contemporary child malnutrition literature, dispute certain quality control maxims of anthropometric child-health surveys, and quantify the responsible latent factors of child malnutrition. These efforts are in service of a better characterization of malnutrition, a more reliable estimate of how many children are malnourished, and a better understanding of the geographical distribution and dynamic stochastic characteristics of malnutrition. It is essential to better understand malnutrition and its causes to suggest appropriate corrective policy. This dissertation consists of four principal essays, each from a unique conceptual perspective. The first essay is a historical and epistemological perspective of the science of anthropometry. I contextualize the legacy of child malnutrition efforts, including the link between eugenics and contemporary notions of “normal” child growth, the institutional power-struggle for child growth chart superiority, the obfuscated distinction between growth references and standards of growth, and the consequences of universal standards that do not reflect observable populations. The second essay is a systematic review of the literature, the largest of its kind to date. I synthesize 184 disaggregate empirical studies of the determinants of child malnutrition in Africa published since 1990. I find numerous opportunities for development within this corpus, in particular opportunities to enrich the scope, scale, and quantification of the field. The third essay is an analytical perspective on the quality control mechanisms applied to anthropometric surveys. I challenge the practice of rejecting datasets based on overlarge z-score standard deviation values and offer an alternative approach. The fourth essay is an econometric empirical analysis in Kenya and Nigeria of child malnutrition determinants. I use spatial Bayesian kriging and four-level random intercept hierarchical logit models to show the spatial heterogeneity of malnutrition prevalence, and to quantify various socio-economic and climatic determinants of child malnutrition. I find significant spatial and hierarchical relationships and determinants, which can move malnutrition rates by over 50%.Item Novel Immunotherapy Agents in Oncology: Generalizability of Trial Results and Drivers of Clinical Utilization(2021) Mishkin, Grace; Franzini, Luisa; Health Services Administration; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Cancer is the second most common cause of death in the United States after heart disease. Novel immunotherapy agents such as nivolumab and pembrolizumab have become an essential, albeit extremely expensive, component of oncology care since their first approvals in melanoma in 2014 and lung cancer in 2015. However, little is known about differences between immunotherapy clinical trial participants and the real-world patient population, or about the drivers of provider utilization of these agents. The first objective of this dissertation used the SEER-Medicare linked database with claims data from 2014-2016 to conduct two aims analyzing potential disparities between Medicare beneficiaries on active treatment for melanoma and lung cancer and Medicare clinical trial participants. Aim one compared the characteristics of Medicare patients on active cancer treatment to Medicare patients on active cancer treatment clinical trials. Aim two compared Medicare patients receiving the novel immunotherapy agents nivolumab or pembrolizumab to Medicare patients participating in trials of these two immunotherapy agents. Because of the demographic differences in the melanoma and lung cancer patient populations, these aims were analyzed separately in melanoma and lung cancer. As hypothesized, patients in clinical trials were significantly younger and had fewer comorbid conditions than patients undergoing active cancer treatment not in clinical trials. Underrepresentation of non-White and female patients in clinical trials was hypothesized, but these results were less consistent. The second objective used Medicare Open Payments data from 2016 and Medicare provider utilization data from 2017 to analyze 1) if industry payments promoting nivolumab or pembrolizumab were positively associated with whether a provider was a high utilizer of the agent, and 2) among these high utilizers, if industry payments were positively associated with greater utilization amounts. The hypothesized results, that industry payments were associated with greater likelihood of high utilization and more utilization among high utilizers, were seen in some of the analyses but not consistently throughout the study. Through unique analyses of recent datasets, this dissertation advances our understanding of potential disparities in clinical trial representativeness and the generally positive relationship between promotional payments and provider utilization of immunotherapy agents in the Medicare cancer patient population.