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    Pathways for the Increased Use of Nature-Inclusive Design in U.S. Offshore Wind Farms

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    Compared to many other countries, offshore wind is still an emerging industry in the United States; however, U.S. offshore wind farm (OWF) capacity is expected to increase dramatically in the coming years. This significant increase in offshore wind capacity will provide clean energy for millions of American households, generate billions in economic benefits, and support states’ climate goals. The use of nature-inclusive design (NiD) approaches could allow OWFs to provide even greater fish and wildlife habitat benefits than can be provided by an OWF that does not incorporate NiD approaches. By supporting robust populations of marine species, the incorporation of NiD elements can then help sustain ocean-based industries that depend on thriving fish, crustacean, and other marine populations. This capstone assesses the benefits and drawbacks of the inclusion of NiD in OWFs, highlights how this approach could be utilized in OWFs within the Bureau of Ocean Energy Management's (BOEM) Atlantic region, details the policies that could be used to advance this approach. The project identified several polices that would be effective at increasing the use of NiD at OWFs in BOEM’s Atlantic region, as well as at fixed bottom OWFs in other BOEM regions, including establishing a federal bidding credit for companies that commit to using NiD approaches, the utilization of non-price criteria in state’s OWF solicitations, and requiring the consideration of NiD elements through BOEM’s Record of Decisions

    PRECISION MEDICINE GUIDED VANCOMYCIN USE AND MONITORING AMONG HOSPITALIZED PATIENTS

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    Therapeutic drug monitoring (TDM) refers to the act of using clinically relevant measurable chemical parameters to predict dosing. The Area Under the Curve to the Minimum Inhibitory Concentration (AUC/MIC) have been shown to directly correlate with bacterial clearance in preclinical models, but troughs have come to be widely used as a surrogate for AUC/MIC in vancomycin TDM. Trough concentrations have shown widely varied and unreliable correlation with AUC/MIC. This dissertation aims to provide a better understanding of the current trough based vancomycin TDM practices and assess the accuracy of an AUC based Bayesian TDM model in the prediction of serum vancomycin concentration. This body of research was conducted in three parts, first a scoping review to assess the current body of literature on vancomycin TDM, and identify research gaps in vancomycin TDM. We identified a limited number of studies assessing trough based and or AUC based TDM monitoring. We also identified some software used in aiding TDM monitoring. The second part was a retrospective chart review to characterize vancomycin use among hospitalized patients and to validate an AUC based monitoring software. We identified some challenges with the timing of vancomycin sample collection for trough based monitoring and suboptimal target therapeutic target trough attainment among hospitalized patients. The final and third part was a prospective study to assess the accuracy of vancomycin serum concentration prediction with an AUC based monitoring software using blood samples collected early in the vancomycin treatment course, before attainment of steady state. We were able to demonstrate the predictive ability of an AUC based TDM monitoring software. We also demonstrated an iterative improvement in the software’s predictive accuracy as more patient specific data was inputted in the software

    HEARING AND VISION LOSS AND ACTIVITY PARTICIPATION AMONG OLDER ADULTS: FINDINGS FROM THE NATIONAL HEALTH AND AGING TRENDS STUDY

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    Background Hearing and vision loss are highly prevalent among older adults and can negatively impact functional ability and quality of life. However, little is known about how sensory loss influences preferred activity engagement, which is crucial for well-being in older adults. Objectives We aimed to evaluate the association between sensory loss status (hearing loss only, vision loss only, or dual sensory loss) and preference for physical versus non-physical activities among older adults. Methods We used data from Round 12 (2022) of the National Health and Aging Trends Study (NHATS), a nationally representative survey of U.S. Medicare beneficiaries aged 65 years and older. Sensory loss was objectively assessed through pure-tone audiometry and vision testing. Participants' favorite activities were categorized as physical or non- physical. Logistic regression models, adjusted for demographic and health-related covariates, were used to estimate the association between sensory loss and preference for physical activities, accounting for survey weights. Results Among 4,640 participants, 38% had no sensory loss, 43% had hearing loss only, 7% had vision loss only, and 13% had dual sensory loss. Walking or jogging was the most commonly preferred activity. In fully adjusted models, dual sensory loss was associated with 30% lower odds of preferring physical over non-physical activities compared to no sensory loss (OR=0.70, 95% CI: 0.57–0.87). Conclusions Dual sensory loss is associated with a reduced preference for physical activities among older adults. These findings suggest the need for targeted interventions that address both individual sensory loss and broader environmental barriers to support active aging and preserve participation in personally meaningful activities

    IMPROVED COOKSTOVES: GLOBAL DEVELOPMENT, INDIGENOUS TECHNOLOGY, AND HEALTH

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    This thesis analyzes six decades of the history to explore the transformation of cookstove technology within the context of global development and international aid, as well as indigenous efforts aimed at improving efficient cooking and health. Billions of people utilize cookstoves daily for food preparation and heating. This thesis aims to answer the questions of how and why cookstove technology evolved in the 20th century. Using published articles, local case studies, oral histories and archival sources covering six decades of local and international efforts to improve cookstove technology, this thesis describes social, economic and political factors leading to changes in cookstove design in global settings. It places modifications to cookstoves both within the context of external efforts on the part of NGOs and intergovernmental bodies to provide foreign aid as well as local efforts to improve health and wellbeing. Additionally, it seeks to utilize cookstove technology to explore or highlight wider changes to developmental assistance from the 1950s to the present. The history of cookstove modification is a part of a larger development narrative in low- and middle-income settings. With each modification the stove was remolded to meet a purpose (i.e. decreased fuel consumption, improved air quality). This thesis also aims to identify discrepancies in intended purpose between foreign developers and local populations. Despite sixty years of development work, uptake of “improved” cookstoves remains inconsistent. Cookstove modifications occurred because of competing priorities by international donors, local government and the populations who utilized these devices. This project leverages several resources that allow for longitudinal assessments of the adaptation of cookstoves and cooking fuel to understand how recurrent agendas including appropriate technology, environmentalism, developmental economics, women’s rights and global health influence modification of stove technology and at times compete. This thesis serves to build on previous work concerning developmental economics in the early 20th century as well as the appropriate technology movement in the mid-20th century. It defines the introduction of cookstoves not as a singular event but rather a technology that morphs, reconstructs, and helps contextualize our understanding of technology and development efforts in the 20th century

    ROLE OF TEMPORALLY RESTRICTED TRANSCRIPTION FACTORS IN RETINAL TRANSCRIPTOMICS AND DEVELOPMENTAL CELL FATE SPECIFICATION

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    The mammalian central nervous system relies on complex signaling networks that drive cognition and problem-solving. Understanding how diverse cell populations arise and interact is crucial for assessing disease pathology. The retina serves as an ideal model for studying these processes and developing neuron-restorative therapies. This thesis reviews recent advances in retinal neurogenesis, emphasizing insights from single-cell multiomic analyses. We explore how extrinsic signals drive transcriptional changes that pattern the optic cup and regulate neurogenesis. Additionally, we examine core, evolutionarily conserved gene regulatory networks (GRNs) that define early- and late-stage retinal progenitor cells (RPCs) and their roles in cell fate determination. Lastly, we discuss species-specific variations in retinal development and key unresolved questions. To address these gaps, it is essential to understand molecular techniques available for studying developmental neuroscience. The Blackshaw lab has pioneered single-cell transcriptomics and genomics, contributing protocols on multiplexed single-cell RNA sequencing and fixed sample scRNA-seq and scATAC-seq. Multiplexing enables cost-effective phenotyping across genotypes or treatments early in investigations. Fixed sample sequencing provides insights into transcriptomic and genomic changes, revealing how gene expression is influenced by chromatin accessibility. Our research focused on transcription factors regulating temporal identity. First, we examined the Kruppel-like factor family, which maintains late-stage progenitor identity. Overexpression during their temporal window expanded progenitor populations while repressing differentiation genes. Next, we studied MEINOX transcription factors, overexpressing them in late-stage development to assess their role in temporal identity shifts. While cell fate specification remained unchanged, we observed significant alterations in progenitor identity and maturation. Lastly, we analyzed NR2F transcription factors, identifying shifts in both cell fate specification and temporal identity through bioinformatics. This work enhances our understanding of temporal identity regulation. These findings provide critical insights into reprogramming strategies, offering a foundation for future therapeutic applications in neuroregeneration

    USE OF GLUCAGON-LIKE PEPTIDE 1 AGONISTS (GLP-1s) AMONG INDIVIDUALS UNDERGOING BARIATRIC SURGERY IN THE UNITED STATES: A RETROSPECTIVE COHORT STUDY

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    Importance: Although randomized and well-controlled observational studies demonstrate the efficacy of glucagon-like peptide 1 agonists (GLP-1s) for weight management after bariatric surgery, little is known regarding the frequency and predictors of such use. Objective: To characterize the use and factors associated with GLP-1 initiation among U.S. adults undergoing bariatric surgery. Design: Retrospective cohort study. Setting: National multicenter database of electronic health records of ~113 million U.S. adults. Participants: Adults undergoing bariatric surgery from 2015 to 2021 who did not use GLP-1s during the 12-months prior to surgery. Exposures: Sociodemographic (age, sex, race, region, etc) and clinical (bariatric surgery procedures, body mass index [BMI], comorbidities, co-medications) factors. Measurements: We first used descriptive statistics to characterize GLP-1 initiation after bariatric surgery. We then used Cox proportional hazards models to identify baseline patient characteristics associated with GLP-1 initiation. We also used time-dependent Cox models to examine the association of post-surgery BMI with GLP-1 initiation. Results: Among 35,286 individuals undergoing bariatric surgery, the mean (standard deviation) age was 47.9 (13.3) years, while 75.1% were female and 62.1% were white. A total of 6,067 individuals (17.2%) initiated GLP-1s after surgery, with approximately 22% beginning within two years of surgery, and the remainder initiating during post-surgical years 3-4 (36%), years 5-6 (27%) or beyond (14%). The overall median BMI before GLP-1 initiation was 37.5 kg/m2 (interquartile range 33.1 – 42.1). In regression models, females (adjusted hazard ratio [aHR] 1.82, 95% confidence intervals [CI] 1.69 to 1.96) and those undergoing sleeve gastrectomy (aHR 1.57, CI 1.48 to 1.67) were more likely to initiate GLP-1 than their counterparts. Each 1 kg/m2 increase in post-surgical BMI was associated with a 7% increase in likelihood of GLP-1 initiation (aHR 1.07, CI 1.07 to 1.08). Conclusion: Among individuals undergoing bariatric surgery, approximately one in eight initiated a GLP-1. Initiation was greater among women, those undergoing sleeve gastrectomy and individuals with larger BMI regain than among their counterparts

    Optimization and Characterization of 3D-Printed Bioreactors for Advanced Cellular Systems

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    This thesis presents the development and characterization of 3D-printed microfluidic bioreactors for advanced cellular systems. Current brain organoid culture methods face significant limitations due to diffusion constraints, restricting structures to diameters below 500 μm before core necrosis occurs. This challenge is addressed through systematic optimization of high-resolution microfluidic platforms that support larger tissue constructs through enhanced nutrient delivery. Using projection micro-stereolithography (PμSL) and stereolithography (SLA) printing technologies, resolution capabilities and channel clearance was characterized across multiple photopolymer resins, demonstrating that BMF Bio resin with PμSL printing achieved features as small as 250 μm with error rates below 10%. This thesis also establishes protocols for post-processing, surface treatment, and sterilization, including UV/thermal curing regimens tailored to specific material properties and PDMS compatibility requirements.Three bioreactor variants were developed: a global perfusion bioreactor incorporating a 5×5 array of microtubes with varying pore sizes, an electrode bioreactor integrating a 3×3 electrode port array for electrophysiological monitoring, and a bacterial bioreactor demonstrating crossover applications to microbial systems. The innovative "jacket" sealing strategy with integrated cell access points effectively eliminated leakage while maintaining experimental accessibility. Validation studies with neural progenitor cells demonstrated successful maintenance of viable cultures for up to 8 weeks, with immunofluorescence analysis confirming both proliferation and differentiation into mature cell types. Perfusion visualization using gelatin hydrogels verified efficient nutrient distribution throughout the culture chambers This work establishes a versatile foundation for uspporting larger, more complex tissue constructs, potentially enabling advanced models for studying neural development, disease mechanisms, and cellular interactions in more physiologically relevant microenvironments

    ECONOMIC INCENTIVES AND ADVERTISING MARKET STRUCTURES IN FOOD POLICY: THE ROLE OF CASH TRANSFERS, FREQUENCY OF PAYMENT, AND TV ADVERTISING IN SHAPING NUTRITIONAL BEHAVIOR

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    Objectives: This dissertation examines how economic incentives and advertising market structures shape food policy and consumer nutritional behavior. The first study evaluates the impact of an unconditional cash transfer (UCT) program on diet quality among elderly individuals. The second study examines how UCT payment frequency influences food purchasing decisions and diet quality. The third study investigates structural disparities in television advertising costs and exposure, comparing the market positioning of healthy and unhealthy foods. Methods: The studies employ quasi-experimental and econometric approaches. The first study applies a Regression Discontinuity Design using the Colombian National Quality of Life Survey (2020–2022) to estimate the effect of UCT participation on diet quality and food expenditures. The second study employs Multivalued Treatment Models (MTM) and Augmented Inverse Probability Weighting to assess the impact of monthly versus bi-monthly UCT payments on food variety and nutritional intake. The third study analyzes Kantar IBOPE Media data (2016–2017), applying cost-per-rating-point (CPP) and Herfindahl-Hirschman Index (HHI) measures to evaluate disparities in food advertising. Results: The first study finds that UCT participation improves diet quality (7%–51%) and protein food purchases (14%) among elderly females, while reducing ultra-processed food consumption (65%) among males. The second study shows that monthly UCT payments enhance dietary diversity, whereas bi-monthly payments lead to a 9.6% lower diet quality. The third study reveals that unhealthy food brands dominate advertising volume and benefit from nonlinear pricing, securing lower costs per rating point. In contrast, healthy food ads face disproportionately higher costs, limiting their market visibility. A market concentration analysis (HHI = 2532) shows that 4% of unhealthy food advertisers control 30% of total food TV ad spending. Policy Implications: These findings have important implications for food policy and public health. Cash transfer programs can improve diet quality among low-income elderly populations, but optimizing payment frequency is essential to maximize their impact. Monthly payments should be prioritized to support better food choices. Targeted subsidies, transparency in ad pricing, and regulatory measures can promote healthier advertising and support equitable food policy

    INNOVATIONS IN MICROFLUIDICS-ENABLED PLATFORMS FOR HIGH-THROUGHPUT BIOASSAYS

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    Microfluidics has emerged as a transformative technology for high-throughput bioassays, offering advantages in sensitivity, automation, and reagent efficiency while enabling precise control of small fluid volumes for biomarker detection, drug screening, and nanoparticle synthesis. However, despite these advancements, current microfluidic technologies face critical limitations across multiple performance metrics, including sensitivity and specificity, scalability, throughput, multiplexing, reagent consumption, reaction manipulation, ease of integration, timescale feasibility, and adaptability to diverse applications. Addressing these challenges, this dissertation presents four distinct microfluidic platforms that enhance high-throughput screening and bioassay performance while overcoming key barriers in existing technologies. First, we developed CRISPR-AMPED (CRISPR-based Amplification via Magnetic Proximity Extension and Detection), a CRISPR/Cas12a-based digital immunoassay that integrates magnetic proximity extension to enable rapid, highly sensitive biomarker detection. This approach enhances target amplification while reducing reaction complexity, achieving attomolar sensitivity for protein detection. Further improvements were realized through a microwell array format, increasing detection precision, minimizing reaction volumes and broadening dynamic range (Chapter 2). Next, we introduced TESLI (Tubing-Eliminated Sample Loading Interface) to improve droplet-based high-throughput screening (HTS). TESLI removes traditional tubing constraints, enabling direct sample spotting, automated droplet generation, and high-throughput analysis with minimal sample loss. We further integrated dual TESLIs into a continuous droplet workflow, minimizing idle time while expanding scalability. This system sets a new benchmark for high- throughput droplet microfluidics (Chapter 3). To advance automated combinatorial drug screening, we developed RoboDrop (Robotic- Printed Combinatorial Droplet System), a robotic-driven microfluidic platform that enables precise droplet deposition and real-time analysis. RoboDrop was validated through antibiotic synergy studies, successfully identifying new three-drug combinations for treating bacterial infections. The system represents a scalable, automation-friendly approach to antimicrobial resistance (AMR) research and drug discovery (Chapter 4). Finally, we developed μLNP-Pur (Microfluidic Lipid Nanoparticle Purification Platform), a continuous microfluidic-enhanced system that enables millisecond-scale purification of lipid nanoparticles (LNPs). This platform provided mechanistic insights into how pH, salt concentration, and solvent polarity influence LNP stability and composition during purification. Additionally, real- time Förster Resonance Energy Transfer (FRET) monitoring allowed for in-depth analysis of LNP fusion dynamics, enhancing our understanding of the LNP production process and its implications for scalable nanomedicine manufacturing (Chapter 5)

    MECHANISTIC INSIGHTS INTO TRANSCRIPTION ACTIVATION BY HISTONE METHYLATION AND DEUBIQUITINATION

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    The reading, writing, and erasing of post-translational modifications on histone proteins plays critical roles in the regulation of transcription. One such example is the delicate coordination of various enzymes to activate transcription in heterochromatin, or transcriptionally silent areas of chromatin. The first step of this process is the removal of the monoubiquitin mark of nucleosomal histone H2A lysine 119 (H2AK119ub), which drives gene silencing and heterochromatin formation. USP21 is one of four major deubiquitinating enzymes that are responsible for the removal of H2AK119ub. Subsequently, histone proteins undergo a cascade of modifications to initiate transcription, including the ubiquitination of histone H2B lysine 120 (H2BK120ub) which stimulates the tri-methylation of histone H3 lysine 4 (H3K4me3) by the Mixed Lineage Leukemia-1 (MLL-1) complex. Although cellular functions of USP21 and MLL1 are known, the molecular mechanisms by which these enzymes specifically recognize and modify nucleosomes are unknown. I have determined the structures of the core MLL1 complex bound to a H2BK120ub nucleosome and the catalytic domain of USP21 bound to a H2AK119ub nucleosome by cryo-electron microscopy and integrative modeling. To this end, I identified critical interactions of both enzymes that facilitates recognition of ubiquitinated nucleosome substrates through biochemical and structural analysis. In addition, I identify mechanisms by which each enzyme is regulated, ranging from complex assembly of MLL1 to auto-inhibition of USP21. Together, these structural and biochemical findings further paint the diverse molecular landscape of chromatin-modifying enzymes by revealing mechanisms of nucleosome engagement and activity

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