American Society for Eighteenth-Century Studies

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    INITIAL TISSUE RESPONSE TO VOLAR FIBROBLAST TRANSPLANTATION IN NON-VOLAR DERMIS

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    This study investigates the early tissue response to volar fibroblast transplantation into non-volar dermis using a mouse model. The central research question is to determine the immediate effects of transplanting volar fibroblasts into non-volar skin, focusing on dermal disruption, immune and inflammatory responses, and donor cell survival. The goal is to establish a baseline for optimizing future fibroblast-based skin therapies. Methods: Primary volar and non-volar fibroblasts were isolated from transgenic mice that express green fluorescent protein (GFP) upon tamoxifen induction. These cells were cultured in vitro to assess confluency, proliferation, and average cell size over a two-week period. For in vivo analysis, 50,000 volar fibroblasts were injected into the ear dermis of recipient mice. Non-volar fibroblasts and media-only injections served as controls. Three days post-injection, tissue samples were harvested and analyzed using Hematoxylin and Eosin (H&E) staining to assess tissue structure and inflammation, and immunofluorescence staining to visualize GFP+ donor cells, DAPI-stained nuclei, and native red fluorescence from tdT+ recipient cells. Results: In vitro, volar fibroblasts exhibited significantly higher proliferation and confluency than non-volar fibroblasts, despite being smaller in size. In vivo, H&E staining revealed dermal disruption at injection sites across all groups, including cartilage damage, tissue expansion, increased vascular density, red blood cell extravasation, and inflammatory cell infiltration. These features suggest acute physical trauma from injection rather than cell-specific remodeling. GFP+ donor fibroblasts were successfully detected in the dermis of recipient mice three days post-injection, confirming short-term cell survival. Conclusions: The findings indicate that three days post-injection is too early to observe biologically meaningful remodeling driven by fibroblast transplantation. The observed changes primarily reflect acute mechanical injury and early immune response. However, the ability to detect viable donor cells at this early time point establishes a clear and reproducible baseline for future studies. This model provides a valuable platform for testing how variables such as cell number and pre-treatment conditions affect fibroblast survival, immune response, and long-term tissue remodeling in skin regeneration research

    Creating Accessible, Patient-Centered Education Materials for Fetal Blood Sampling and Intrauterine Transfusion

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    Fetal anemia, caused by conditions such as hemolytic disease of the fetus and newborn (HDFN) or parvovirus B19 infection, can lead to severe complications, including hydrops fetalis and fetal death. The most common treatment for fetal anemia is intrauterine transfusion (IUT), a lifesaving but historically risky intervention with limited patient-friendly educational resources. Existing materials often lack visual aids, are text-heavy, or contain outdated information, contributing to patient anxiety and knowledge gaps. This study aimed to create and evaluate an animated educational video to improve patient understanding of IUT, reduce anxiety, and promote self-advocacy. The animation was designed using evidence-based multimedia learning principles and assessed for educational value and emotional impact. The animation was developed with iterative feedback from clinicians, patient stakeholders, and the Patient Education Material Assessment Tool for Audiovisual Material (PEMAT-A/V). A 5-minute animation depicting an overview of a typical IUT procedure at a high-volume fetal therapy center was produced. A study was conducted with 11 participants, including IUT-experienced and inexperienced individuals, to evaluate the video’s understandability (via the PEMAT-A/V) and emotional impact (via Likert scales and open-response feedback). The animation scored 97.5% on the PEMAT-A/V, exceeding the 70% threshold required for effective educational materials. Participants rated it 4.5/5 stars and reported overall positive emotions (e.g. calmness, confidence) despite some anxiety-related responses. Key strengths included clear visuals of needle placement and explanations of medical terms. Feedback highlighted opportunities to expand content (e.g. complications, support resources) and adjust tonal elements (e.g. voiceover style). This animation serves as an accessible patient education tool that improves understanding of IUT while reducing anxiety. It also demonstrates how patient-centered multimedia resources can bridge critical information gaps for rare medical procedures, ultimately empowering patients, improving informed consent, and setting a model for similar fetal therapy education initiatives. Future directions include increasing survey sample size, iterating further based on survey feedback, and eventually hosting the animation on the Johns Hopkins Center for Fetal Therapy website and YouTube channel for increased accessibility and credibility

    Career Education and Employment Outcomes: A Multidimensional Study of the School-to-Work Transition, Teacher Influence, and Career Education Practices in the Midwest

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    This dossier is composed of three parts. In Part 1, the author conducts a literature synthesis to understand the factors contributing to unemployment for Black and Latinx high school graduates transitioning from school to work. Based on findings from the first project, Part 2 contains a mixed-methods needs assessment that examines educator attitudes and activities related to career education to understand a possible contributing factor to graduate unemployment. Finally, Part 3 is a qualitative content analysis focusing on the career education policies, statutes, and guidance documentation that informs career learning across eight midwestern states linked through their labor markets

    THERMODYNAMICS OF BETA BARREL MEMBRANE PROTEIN FOLDING INSIGHTS INTO HYDROXYL SIDE CHAINS AND INTERMEDIATE STRUCTURES

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    Membrane proteins are vital for cellular functions, with their thermodynamic stability and folding mechanisms playing key roles in their activity. This dissertation explores the energetic contributions of hydroxyl residues in lipid-facing environments and the folding mechanism of outer membrane proteins (OMPs) in Gram-negative bacteria. Using a host-guest system, we measured side chain transfer energies for serine and threonine residues, revealing that -OH groups are most destabilizing at the bilayer center and less so near the interface. From all atom molecular dynamics simulation, we found the -OH energies are determined by both local polar atom concentration and exposure to the bilayer. These findings align with knowledge-based models and provide a framework for understanding membrane protein thermodynamics. Additionally, we characterized a partially exposed intermediate of OmpLA during chemical denaturation, demonstrating distinct microenvironments for lipid-facing sites and uncovering new insights into lipid-protein interactions and β-barrel folding. This work advances the understanding of membrane protein stability and folding, with implications for drug discovery, protein design, and biotechnological applications

    Modeling the Effect of Sleeve Gastrectomy on Gastric Digestion in the Stomach: Insights from Multiphase Flow Modeling

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    The geometry and motility of the stomach play a critical role in the digestion of ingested liquid meals. Sleeve gastrectomy, a common type of bariatric surgery used to reduce the size of the stomach, significantly alters the stomach’s anatomy and motility, which impacts gastric emptying and digestion. In this study, we use an imaging data-based computational model, StomachSim, to investigate the consequences of sleeve gastrectomy. The pre-operative stomach anatomy was derived from imaging data and the post-sleeve gastrectomy shapes were generated for different resection volumes. We investigate the effect of sleeve sizes and motility patterns on gastric mixing and emptying. Simulations were conducted using an immersed-boundary flow solver, modeling a liquid meal to analyze changes in gastric content mixing and emptying rates. The results reveal that different degrees of volume reduction and impaired gastric motility have complex effects on stomach's mixing and emptying functions, which are important factors in gastric health of the patient. Specifically, the total gastric liquid emptying rates increased by 21% with a 30% volume reduction and by 51% with reductions exceeding 50%, due to altered intragastric pressure. Additionally, impaired motility functions resulted in slower mixing, leading to delayed food emptying. These findings provide insights into the biomechanical effects of sleeve gastrectomy on gastric digestion and emptying functions, highlighting the potential of computational models to inform surgical planning and post-operative management

    The Systems Behind the Scholarships: The Role of Community-Based Educational Organizations in Furthering Social Justice

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    A society’s health, prosperity, and capacity to thrive depend heavily on the engagement of its citizens in economic activity. Education is integral in preparing young people to become economic contributors, and a four-year college degree is linked to a greater capacity for earnings over the course of one’s lifetime. Equitable access to the pursuit and attainment of a degree and subsequent economic participation thus not only represents a matter of social justice, but a necessary condition for a flourishing society. In the United States, wide disparities exist between the rate of degree acquisition by students from low-income backgrounds and that of their higher income peers. Organizations in the nonprofit sector play an important role in addressing such disparities by providing college access and support services to historically marginalized young people, including low-income, first-generation students. However, the processes and practices of the nonprofit sector largely remain uninterrogated for the production of optimal outcomes and potentially unintended consequences. This paper provides insight into the inner workings of community-based organizations (CBOs) through two original inquiries: an in-depth analysis of a CBO’s operational practices, conducted through observer participation and ethnographic methods, and a qualitative study of the student selection processes of five CBOs that serve low-income, first-generation students. The studies reveal that a CBO’s processes and practices may be informed by historically American social narratives and broader ideologies that are harmful to low-income individuals, which are then amplified and expressed through the organization’s programs, services, and communications. Secondly, CBOs’ practices are frequently shaped by the organizational pressures of resource dependence and the need for legitimacy, and tend to reinforce broader social systems, focus on the individual, and capture organizational benefit. Finally, leaders in CBOs navigate substantial ambiguity when designing and delivering their programs and services, and rely on the discretion of staff and volunteers in the execution of many of their processes. The paper concludes with four actionable recommendations for practitioners

    Trajectories of PrEP Engagement Among Female Sex Workers in South Africa: A Data-Driven Exploration

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    Background: Female sex workers (FSW) in South Africa are disproportionately affected by HIV, with a prevalence around 60%. Daily oral pre-exposure prophylaxis (PrEP) can reduce HIV acquisition by over 90% with optimal adherence. Understanding longitudinal patterns of PrEP use and the characteristics of individuals following distinct trajectories is essential to inform targeted interventions. Methods: We analyzed routine programmatic data from TB HIV Care (THC), a South African non-profit HIV service provider. Records from 6,866 FSW initiating PrEP across nine sites (2018–2021) were used to examine PrEP engagement over 12 months. Engagement was defined as having a follow-up visit within 40 days of the previous visit. Group-based trajectory modeling (GBTM) identified longitudinal patterns of engagement. Baseline demographic and psychosocial variables were compared across trajectory groups. Results: Two distinct PrEP engagement trajectories were identified: rapid disengagement (68.3%) and gradual disengagement (31.7%). Rapid disengagement, comprising 73% disengagement by month 2; and gradual disengagement, comprising a slower decline in engagement whereby 90% disengaged by month 5. Most women initiated PrEP and did not return for subsequent visits. Younger age (18–24) was associated with rapid disengagement, while older women and those from certain sites were more likely to show prolonged engagement. Descriptive analysis of psychosocial and behavioral factors showed minimal differences between groups. Baseline self-reported condom use was more common in the gradual disengagement group, and sex under the influence of substances was very common in both groups. Interpretation of these findings was limited by substantial missingness in behavioral data due to variability in clinical form usage. Conclusion: Most FSW in South Africa discontinue PrEP within three months of initiation, and nearly all discontinue within a year. Tailored strategies supporting PrEP persistence and re-engagement, especially for younger FSW and those facing structural barriers, are needed to enhance the effectiveness of PrEP programs in real-world settings

    Language, Equity, and Assessment in Gifted and Talented Education

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    Gifted and talented education occupies a highly contested space in research, policy, and practice because of how the field historically has been employed to withhold opportunities and perpetuate structures of exclusion and inequity. This dissertation probes the influence that language bias may have on gifted and talented identification, and it forms a narrative about how language bias is understood and experienced in the field. The dissertation opens with a literature review on equity in education and continues with three studies examining one form of inequity, language bias, in gifted and talented education. The studies are a systematic review of the gifted and talented literature, a differentiated qualitative replication interview study with educators of the gifted and talented, and an original qualitative cognitive interview study with gifted and talented students. The findings from the studies are summarized and connected in the concluding chapter. This work revealed that language bias is insufficiently studied and inconsistently defined even though the influences of language are keenly felt by both educators and students. Moreover, the findings indicate that the field needs to unravel how it has intertwined language and culture and the assumptions related to language, culture, and bias that have underpinned previous research in the gifted education landscape. The findings also suggest that creativity and context can be in competition in testing environments, and patterns that are correlated with divergent thinking and access to relevant learning opportunities may underlie incorrect responses. My findings add texture to the conflicted findings about the appropriateness of using such a measure for GT identification, and they challenge the commonly-held perception that nonverbal measurements are language-free measures that serve students from diverse language backgrounds equally well. Specifically, the findings counter the belief that removing written text from a test is equivalent to removing the presence of language from the testing experience. I argue that consensus around a definition for language bias is the first critical step in advancing the field, and I conclude this dissertation by offering a possible definition for the term. I also argue that the field will benefit from increasing innovation in how we conduct research, and I propose integrating more open science practices (e.g., replication) in education research, especially qualitative research, to expand our knowledge and inform best-practices for the field

    Environmental Localization, Mapping, and Guidance for Visual Prosthesis Users

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    A human-centric navigation system has been developed with a focus on supporting blind users of prosthetic vision devices by providing these users the ability to navigate their environment independently. The system maps the environment and localizes the user while incorporating context-enhanced information about the scene generated by AI-based methods. A deep learning semantic segmentation engine is utilized to process information from RGB and incorporates depth imaging sensors to produce semantic mappings of the scene. The heightened level of environmental interpretability provided by semantic mapping enables high-level human-computer interactions with the user, such as queries for guidance to specific objects or features within the environment. Unlike traditional sensor-based mapping frameworks that represent the environment as simple occupied / unoccupied space, our semantic mapping approach interprets the identity of occupied space as specific types of objects and their regional association to region types (e.g., static, movable, dynamic). The semantic segmentation also enables contextually-aware scene processing, which our framework leverages for robust ground estimation and tracking with fused depth data to distinguish above-ground obstacles. To help address the highly limited vision performance of current prosthetic vision technology, the processed depth information is used to generate augmented vision feedback for the prosthetic vision user by filtering out ground and background scene elements and highlighting near-field obstacles to aid in visual identification and avoidance of obstacles while navigating. Supplemental user feedback is provided via a directional haptic headband for path following along autonomously computed trajectories towards desired destinations and voice-based notifications paired with spatial sound for additional information, such as obstacle alerts. An optimized architecture enables real-time performance on a wearable embedded processing platform, which provides high-fidelity update rates for time-critical tasks such as localization and user feedback while decoupling tasks with heavy computational loads. Substantial speed-up is thereby achieved compared to the conventional baseline implementation. The user feedback mechanisms, in conjunction with the navigation software framework, were tested for navigating a human user through a mapped scene, showcasing a holistic understanding of how each component contributes to the overall user experience and navigation performance and highlighting the framework’s potential to enable spatial navigation for visually impaired individuals

    SITE-SPECIFIC MECHANISMS GOVERN BRAIN AND PERIPHERAL ANTIRETROVIRAL THERAPY METABOLISM AND TRANSPORT

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    Neurologic deficits associated with human immunodeficiency virus (HIV) infection demonstrate the need to eliminate viral reservoirs in the brain. Tenofovir (TFV), emtricitabine (FTC), and dolutegravir (DTG) are first-line antiretroviral therapeutics (ART) prescribed for the treatment and prevention of HIV. While these ART drugs distribute across the brain, the mechanisms that contribute to their disposition remain unknown. Here, we demonstrate site-specific metabolism and transport at the blood brain barrier (BBB) that is driven by astrocytes as a primary mechanism that may influence ART disposition by expressing differentially active ART metabolizing enzymes and transporters between primary human BBB cells. We used proteomics by liquid chromatography-mass spectrometry (LC-MS) and functional assays to measure differentially active nucleotide metabolizing kinases and transporters between BBB cells, including brain microvascular endothelial cells (BMVEC), pericytes, and astrocytes. These findings demonstrated the distinct pharmacological capabilities of BBB cell types that contribute to ART metabolism and transport in the brain. Functional assays also demonstrated that BBB cells and astrocytes isolated from rhesus macaque brains possessed cell-dependent capabilities to activate TFV and FTC to their pharmacologically active metabolites. Next, we demonstrated that expression of first-line ART metabolizing enzymes and transporters across brain regions harvested from mouse and rhesus macaques was largely comparable. Additionally, our proteomics analyses demonstrated that BMVEC and pericyte abundance was comparable across brain regions whereas astrocytes were enriched in a site-specific manner. These results suggested that site-specific mechanisms of drug metabolism and transport were localized to the BBB, particularly in astrocytes, rather than in brain tissue. We then demonstrated that drugs of abuse, age, HIV, and ART may differentially modulate ART metabolizing enzymes and transporters at the BBB, brain and periphery, which may also contribute to the site-dependent mechanisms that impact ART availability. Together, this body of work identifies site-specific drug metabolizing and transport mechanisms at the BBB that may determine variable ART disposition in the brain and are distinct from peripheral organs. Further, we provide multifactorial considerations for evaluating ART availability in the CNS in the context of HIV, drugs of abuse, age, and therapeutic intervention

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