University of North Carolina Hospitals

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    Reproducing Racial Commonsense regarding “Asian” in Social Interactions

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    This dissertation project adopts an interactionist approach to examine how members of Asian populations collaboratively construct and negotiate racial commonsense associated with the “Asian” category in the US context. I employ a three-chapter format for my dissertation, and each of my dissertation chapter utilizes a different type of interactional data to address one specific question related to “being Asian” in the US context: 1) how do members of Asian populations orient to and negotiate a shared understanding of the relative group positioning of Asians in the contemporary US racial order?; 2) How do members of Asian populations collaboratively construct shared meanings associated with “being Asian” while orienting to within Asian heterogeneity, thereby drawing boundaries against other racial groups while maintaining within-group distinction ?; 3) How do members of Asian populations display and negotiate their attitudes towards racial policies that may affect members of the Asian category as a whole? With each chapter focusing on a unique dimension of racial commonsense regarding the “Asian” category, the three chapters together offer a detailed account of how members of the “Asian” populations make the ethnic/racial group “Asian” from within and how such members’ work contributes to the making of the contemporary racial order in the U.S. context beyond the Black-White binary. The dissertation illustrates how the meticulous work of positioning one’s own group in relation to other racial groups in a national context, of finding commonalities among co-members while embracing subgroup identities, and of forming and negotiating a view towards policies that affect one’s co-members always happen in concrete situations, where various stocks of generalized knowledge and expectations, some regarding race some not, inevitably intersect with tasks and concerns specific to the local settings of interaction.Doctor of Philosoph

    Spatial and Seasonal Dynamics of Methane in the Neuse River-Pamlico Sound Estuary

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    Methane is a potent greenhouse gas that can have substantial sources from aquatic ecosystems. However, little is known about methane stocks and their spatial and seasonal dynamics in estuaries. While extensive eutrophication and phytoplankton dynamics research has been conducted on the Neuse River–Pamlico Sound (NRPS) estuary, methane concentrations and the associated microbial community remain poorly characterized. We quantify spatiotemporal changes in methane across the NRPS and show that concentrations tend to decrease along the salinity gradient and from surface to bottom waters, suggesting that microbial oxidation and/or degassing is occurring in the water column. We demonstrate that methane concentrations are higher in the summer compared to spring. Along the NRPS, methane concentrations correlate with physicochemical variables. These patterns highlight the important variability in methane distribution in estuarine systems and underscore the need for further research into the microbial community composition and environmental factors influencing methane cycling in estuaries.Master of Scienc

    Leveraging Smart Technology: Designing a Phone-Based Turbidimeter for Safer Water Access

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    Turbidity measures the opacity of water and can indicate potential microbial contamination in both surface and well water. Turbidity is typically measured using turbidimeters or secchi disks; however, these can be costly, cumbersome, and/or complex to use. A low-cost, user-friendly turbidity sensor could provide a useful option for individuals interested in timely and cost-effective data about potential microbial contamination in drinking and surface waters. We developed and piloted a low-cost (<$5) turbidimeter comprised of a graduated cylinder and water-proof, high-contrast sticker, used in conjunction with a mobile phone camera and ImageJ to approximate turbidity. Mean-gray and circularity values were quantified, and a standard curve produced including seven points from 0.10 to 100NTU. In the field, gray value difference provided more reliable estimates at higher turbidity levels and circularity for low turbidity. Currently, neither approach replicates the accuracy of standard equipment, therefore, future efforts should seek to advance reliability and usability.Master of Scienc

    The 2016 Zika Epidemic in León, Nicaragua: Spatial Distribution, Predictors, and 4-Year Neurodevelopmental Impact on Children Exposed to Zika Virus in utero

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    Zika virus (ZIKV) is a flavivirus transmitted between humans by Aedes mosquitoes and whose typical clinical presentation includes fever, rash, conjunctivitis and joint pain. A 2015-2016 epidemic in the Americas exposed large numbers of susceptible individuals to ZIKV and revealed an association between ZIKV exposure in utero and a variety of congenital defects and early developmental issues subsequently classified as “congenital Zika syndrome.” The first aim of this research examined the spatial distribution and predictors of ZIKV seropositivity among participants in an observational cohort that prospectively followed mother-infant pairs in León, Nicaragua from 2017 through 2023. This analysis found that the majority of enrolled women were seropositive for ZIKV, and while there was spatial autocorrelation and variation in seropositivity, there were no statistically significant hotspots. Few individual or household-level characteristics were significant predictors of seropositivity, although prior arboviral infection and the use of public wells were associated with seropositivity while outdoor spraying of insecticides by the Ministry of Health was inversely associated with seropositivity. The most significant predictors observed were at the neighborhood level, where vector control activities such as indoor and outdoor application of insecticides by the Ministry of Health were inversely associated with seropositivity.The second aim followed the children of mothers enrolled in León as well as a second cohort in Managua through 48 months of age to assess neurodevelopmental outcomes among children with ZIKV exposure in utero, but without congenital Zika syndrome at birth. Early Learning Composite and subdomain-specific scores on the Mullen Scales of Early Learning neurodevelopmental assessment were compared between exposed and unexposed children, adjusting for potential confounders using inverse probability weighted generalized estimating equations. No statistically significant differences between ZIKV-exposed and -unexposed children persisted at 36 or 48 months of age, suggesting that differences in neurodevelopment previously observed in the first two years of life may resolve as children reach preschool age. The results of this research emphasize the importance of coordinated public health and vector control interventions in the prevention of ZIKV infection, and of follow-up with ZIKV-exposed children to ensure adequate developmental support during the first years of life.Doctor of Philosoph

    THE RADICAL FAR-RIGHT AND CLIMATE CROSSROADS: SHIFTS IN CLIMATE CHANGE POLICY IN THE U.S. AND EU

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    Radical far-right (RFR) parties have grown constituencies worldwide, showcasing their detestment for meaningful climate change policies through their rollback of environmental protections. This thesis examines the influence RFR parties, and their use of populist framing, in the U.S. and EU have on policies to achieve international climate goals. It qualitatively analyzes the historical context and ideological foundations of RFR parties through a mixed-methods approach, and party manifestos and rhetoric in a quantifiable score against emissions. The foundations are laid in collective action theory, the implementation of a K-group, and how these parties challenge climate milestones and foster skepticism toward international agreements under a two-level game theory, examining the interplay between domestic politics and global climate governance in an era of rising populism. This analyzes if/how RFR parties may pose challenges to international cooperation through their alignment of nationalist agendas with anti- establishment rhetoric, potentially hindering collective climate action.Master of Art

    Understanding Associations Between Patient‐Level Factors and Participation in a Breast Cancer Clinical Trial

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    Background Although breast cancer (BC) clinical trials offer novel treatments, participating patients often do not represent populations seen in clinics. This study assessed how patient sociodemographics, attitudes, and knowledge about clinical trials may be associated with participation. Methods This cross sectional analysis used survey data collected August–September 2021 by Translational Breast Cancer Research Consortium (TBCRC) and December 2022 by Patient Advocate Foundation (PAF) among women with a BC diagnosis. Respondents reported BC clinical trial participation, Attitudes Toward Cancer Trials Scale, clinical trial knowledge, diagnosis age, race, education level, household income, employment status, and BC stage. Descriptive and bivariate analyses were conducted using Cramer's V or Cohen's d as effect sizes. Standardized total effects ( b Tot ) were estimated using a prespecified Structural Equation Model with 0.1, 0.3, and 0.5 indicating weak, medium, and large magnitude, respectively. Results Of 612 respondents, 26% were Black, Indigenous, or a Person of Color, 44% < Bachelor's degree, and 48% had incomes < $50,000. Respondents who reported trial participation (18%) more often had positive attitudes toward trials (mean 94 of 126, SD 19.3 vs. 86, SD 15.5; d = 0.48) compared to those not reporting participation. Positive attitude was associated with trial participation for both survey cohorts (TBCRC: b Tot = 0.22, p = 0.0002; PAF: b Tot = 0.13, p = 0.01). Furthermore, clinical trial knowledge was associated with attitudes (TBCRC: b Tot = 0.27, p = < 0.0001; PAF: b Tot = 0.15, p = 0.003). Discussion Although we found that positive attitudes and high knowledge were associated with clinical trial participation, it is unknown if the trial itself directly affected this. However, trial enrollment may be increased and diversified via future interventions focused on promotion of positive attitudes toward clinical trials, potentially through increased trial education and knowledge

    Feasibility of Intravaginal Artesunate as an Adjuvant HPV & Cervical Precancer Treatment Among Women Living With HIV in Kenya: Study Protocol for a Phase II Clinical Trial

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    Introduction Cervical cancer disproportionately affects women in low- and middle-income countries (LMICs), who account for 90% of deaths from the disease. Human papillomavirus (HPV) is responsible for 99% of cervical cancer cases. Women living with HIV (WLWH) have a higher risk of persistent HPV infection and a greater likelihood of developing cervical cancer. Prevention of cervical cancer requires effective screening and precancer treatment programs. In LMICs, the common treatment method for cervical precancer is thermal ablation. However, for WLWH, thermal ablation is associated with high rates of persistent HPV infection following treatment, a key risk factor for precancer recurrence. Adjuvant topical treatments with cytotoxic or antiviral properties may reduce HPV persistence following ablation. Preclinical and early-phase clinical trials indicate that topical artesunate is active against HPV-associated anogenital lesions, including cervical precancer, and can induce HPV clearance. Consequently, intravaginal artesunate may improve HPV clearance following thermal ablation, although no clinical trials have investigated this. Methods We are conducting a phase II, double-blind, randomized, placebo-controlled trial among 120 HIV seropositive women in Kenya to investigate the feasibility of self-administered intravaginal artesunate pessaries as adjuvant therapy following thermal ablation treatment for cervical precancer. The primary outcome is type-specific HPV clearance 6 months after randomization. Secondary outcomes are safety, adherence, acceptability, uptake, and retention. Participants will be enrolled at least 4 weeks after ablation and will self-administer pessaries on weeks 1, 3, and 5, with alternating drug-free weeks. Study follow-up will extend to 24 weeks after randomization. Conclusion High rates of persistent HPV infection in WLWH is a key limitation of thermal ablation, the most accessible cervical precancer treatment in LMICs. This trial will investigate the feasibility of repurposing topical artesunate as an adjuvant therapy to improve HPV clearance following thermal ablation in WLWH. Trial Registration ClinicalTrials.gov identifier: NCT0651999

    Evaluation of potential biomarkers during irinotecan-based systemic treatment for colorectal cancer—study protocol of the OPTIMA study

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    Background Patients with advanced colorectal cancer (CRC) commonly receive irinotecan-based systemic treatment to alleviate symptoms, improve quality of life (QoL), and prolong overall survival (OS). However, predicting efficacy and toxicity of the treatment is challenging. Previous research indicated an association between the tumor molecular profile and response to irinotecan-based systemic treatment. Moreover, the UGT1A1 genotype of the patient, and the activity of the gut microbial enzyme β-glucuronidase (GUS) have been suggested as biomarkers for the development of systemic (e.g. neutropenia) and gastrointestinal toxicity (e.g. diarrhea) respectively. Therefore, the OPTIMA study will evaluate in patients with advanced CRC: 1) whether tumor molecular profiling can predict the efficacy of irinotecan-based systemic treatment; 2) whether high bacterial GUS enzyme activity is associated with increased gastrointestinal toxicity, decreased QoL and OS; as well as 3) the safety of a 70% irinotecan dose intensity in UGT1A1 poor metabolizers (PMs).MethodsThis prospective, observational, multi-center cohort study will include patients with advanced CRC scheduled for irinotecan-based systemic treatment. Archived tumor tissue and routine CT/MRI scans at baseline and after four cycles will be used to investigate the association of tumor molecular profile and treatment response according to RECIST. Before treatment initiation, germline DNA obtained from whole blood will be genotyped using PCR to determine the UGT1A1*28 genotype, followed by 30% irinotecan dose reduction in UGT1A1 PMs. Bacterial GUS activity will be quantified in fecal samples collected before and during treatment by means of an enzyme activity assay and will be related to patient-reported gastrointestinal toxicity (mainly diarrhea). Additionally, patients will fill in questionnaires concerning QoL, medication use, medical history and comorbidities, dietary habits, as well as physical performance. OS will be documented, capturing the duration from the start of treatment until death from any cause. Discussion Results obtained in the context of the OPTIMA study are expected to contribute to the optimization of efficacy and the reduction of toxicity of irinotecan-based systemic treatment, thereby potentially improving QoL of patients. Given that maintaining QoL is particularly critical in the palliative setting, the OPTIMA study has the potential to be of significant benefit for patients and their caregivers. Trial registration This trial is registered in the ClinicalTrials.gov register (NCT05655780) on December 16th, 2022

    Physical Activity, Symptoms, Quality of Life and Exercise Program Preferences in People With Chronic Lymphocytic Leukaemia

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    Chronic lymphocytic leukaemia (CLL) has a heterogeneous lifelong course. While some patients never require treatment, most experience intermittent periods of active monitoring with other time points in active treatment. Most patients experience significant symptoms which negatively impact their quality of life (QoL). Although physical activity and exercise may help manage symptoms, it is unclear what disease‐related factors drive the physical inactivity observed in people with CLL. This study explored physical activity among people with CLL and assessed differences and relationships in treatment stage, symptoms, quality of life, and preferences for physical activity using an online questionnaire. A total of 128 individuals with CLL [66 M/62F: mean age 67 ± 9.1 years (range 38–91 years)] completed the questionnaire. Those who are being/have been treated (N = 55) exhibited worse QoL (p = 0.018) and lower engagement in higher levels of physical activity (p = 0.045) when compared to their treatment naïve (N = 73) counterparts. Both groups had similar symptomology, with fatigue (∼77%) and insomnia (∼55%) being the most reported and associated with less likelihood of being physically active. Physically active participants reported better QoL (p = 0.020), physical functioning (p = 0.003) and role functioning (p = 0.020) as well as lower levels of fatigue (p = 0.036), pain (p = 0.017) and symptom burden (p = 0.026) compared to those who were insufficiently active. Although 79% of respondents wanted to engage in exercise programs for their CLL, 70% reported never receiving exercise guidance from their healthcare professionals. These findings highlight a significant need for targeted interventions to increase physical activity, likely improving QoL, in people with CLL. Furthermore, there is considerable interest from the CLL community in receiving exercise guidance; however, factors such as treatment status and symptomology should be considered when developing CLL‐specific exercise programs

    CSPG4.CAR-T Cells Modulate Extracellular Matrix Remodeling in DMD Cardiomyopathy

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    Targeting fibrosis in Duchenne muscular dystrophy (DMD)-associated cardiomyopathy is a critical outstanding clinical issue, as cardiac failure remains a leading cause of death despite advances in supportive care. This study evaluates the therapeutic efficacy of CSPG4-targeted chimeric antigen receptor (CAR) T cells in reducing cardiac fibrosis and improving heart function in a preclinical model of the disease. DMD is a progressive genetic disorder characterized by degeneration of skeletal and cardiac muscle. Cardiomyopathy, driven by fibrosis and chronic inflammation, is a leading contributor to mortality in affected patients. Proteoglycans such as CSPG4, critical regulators of extracellular matrix dynamics, are markedly overexpressed in dystrophic hearts and promote pathological remodeling. Current treatments do not adequately target the fibrotic and inflammatory processes underlying cardiac dysfunction. CSPG4-specific CAR-T cells were engineered and administered to dystrophic mice. Therapeutic efficacy was assessed through histological, molecular, and echocardiographic analyses evaluating cardiac fibrosis, inflammation, innervation, and overall function. Treatment with CSPG4 CAR-T cells preserved myocardial integrity, improved cardiac performance, and reduced both fibrosis and inflammatory markers. The therapy also restored cardiac innervation, indicating a reversal of neural remodeling commonly seen in muscular dystrophy-related cardiomyopathy. CSPG4-targeted CAR-T therapy offers a novel, cell-based strategy to mitigate cardiac remodeling in dystrophic hearts. By addressing core fibrotic and inflammatory drivers of disease, this approach represents a significant advancement in the development of precision immune therapies for muscular dystrophies and cardiovascular conditions

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