American Society for Eighteenth-Century Studies

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    POLITICS INFLUENCE LATIN AMERICA’S ONGOING VENEZUELAN MIGRATION CRISIS: COMPARATIVE STUDY OF COLOMBIA AND PERUS RESPONSE

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    Venezuelan migration has turned from a normative migration pattern of people leaving to seek work and educational opportunities to an ongoing crisis as the deterioration of the government, economy, and security continues to drive out millions. Hosting this overwhelming group of migrants has become the responsibility of neighboring countries already struggling with their internal challenges of poverty, unemployment, violence, and inequality. Initially, governments welcomed Venezuelans migrants and provided legal pathways for residency. However, the diaspora’s magnitude and speed amplified existing structural problems, leading to a shift in host countries’ response as they began enacting restrictions. This thesis examines the factors that influenced a variation in migration policies between Colombia and Peru and how the responses have evolved as political transitions occurred and the number of migrants increased overtime. A combination of historical, legal, and discourse analysis methods was utilized to discover how politics has influenced migration policy in the region—political migration theories in combination with a deep analysis between regional affairs and historical relations. The study concludes that the shift towards increased restrictions and the rise of xenophobia occurred due to the surge of migrants, followed by the Covid-19 pandemic, which intensified economic and social challenges. This thesis challenges previous researchers’ conclusions that the variation in Colombia’s pro-migration policies and Peru’s increased restriction is due to historical ties and highlights the effects that domestic, bilateral relations, and political transitions i

    Beyond Urban Fatalities: An Analysis of Shootings by Police in the United States

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    Shootings by police are an under-examined and unequally experienced source of firearm injury, accounting for at least 1 in 20 US homicides and untold nonfatal injuries. Urban and rural areas are implicated, but the circumstances surrounding non-urban shootings are not well known, nor are the modifiable social conditions and potential policy levers for systematic and nationally inclusive injury prevention. This dissertation analyzes a novel dataset, built from the Gun Violence Archive, of all injurious shootings by US police from 2015-2020. The analyses directly compare fatal and nonfatal incidents and injuries; injuries in urban, suburban, and rural areas; and multiple levels of social and policy correlates of local injury incidence on a national scale. On average, 1,770 people were injured annually. Fifty-five percent of shootings were fatal; 45% occurred in predominantly rural zip codes. Lethality was highest in rural areas. Racial disparities in total injury burden were identified across the urban-rural continuum and exceeded estimates drawn from fatal injuries alone. Co-occurring behavioral health needs were associated with 23% of incidents and 38% higher odds of fatal injury. Permit-to-purchase (PTP) statutes and concealed carry (CCW) licensing were associated with lower county injury incidence. For each percentage increase in adults with unmet substance use needs in a state, a 25% increase in county injurious shootings was observed. To prevent injuries from shootings by police, policymakers should prioritize stronger CCW and PTP statutes, investments in programs to elevate the status of vulnerable residents, and non-policing crisis response systems. Urgent need for mandatory reporting of shootings by police persists. Future research should prioritize improving problem-definition related to behavioral health needs, firearm involvement, urban/rural manifestations, and long-term injury consequences. Intervention research should prioritize studies of the effects of police unions, pandemic disruptions, extreme risk protection orders, and emerging crisis-response innovations on injuries from shootings by police

    Bioreducible Polymer-based Nanoparticle for Intravitreal Retina Gene Delivery

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    In a concerted effort toward effective retinal gene therapy, an adeno-associated virus (AAV)-based product has recently received FDA approval for the treatment of rare retinal disorders. However, more than 2.2 billion people worldwide experience visual impairment for a variety of reasons. AAV also has several disadvantages, such as small packaging capacity, immunogenicity and huge economic burden. Additionally, most current clinical retinal gene therapies involve subretinal injection, which is highly invasive, often cause ocular damage, and limit spatial coverage to the vicinity of the injection site. Intravitreal injection has emerged as an alternative means of administration with the advantages of being less invasive, relatively safe, and potentially providing extensive gene delivery across the entire retinal surface area. Here, we developed intravitreal gene delivery nanoparticles (NPs) for a wide range of retinal gene therapy applications. Bioreducible poly(disulfide amine) (PDSA) was synthesized by ring-opening polymerization and sidechain modification. PDSA NP showed significantly greater in vitro reporter transgene expression compared to other lead synthetic formulations with an excellent safety profile, presumably by promoting intracellular plasmid release. PEG-PDSA NPs, by resisting adhesive interactions with vitreous, exhibited markedly greater diffusion rates in rabbit vitreous compared to PDSA NPs. In vivo transfection of NPs showed that PEG-PDSA NPs provided robust reporter transgene expression with widespread retinal coverage in mouse eyes, following intravitreal injection. Lastly, PDSA NPs modified with various amine containing side chains were evaluated with in vitro transfection test. As a result, PEG-PDSA NPs administered intravitreally demonstrated efficient reporter transgene expression. PDSA can serve as a broadly applicable delivery platform for gene therapy of ocular diseases

    Of Cabbages & Kings: An Exploration of Vibriosis as an Occupational Health Hazard for Watermen & Seafood Processors in the Chesapeake Bay, USA

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    United States (U.S.) fisheries represent one of the most lucrative industries, supporting millions of jobs and billions in commercial sales, including imports and exports. It also is one of the most dangerous industries. The specific types of injuries – e.g., musculoskeletal, wounds, microbial, etc. – are not delineated in official U.S. Bureau of Labor Statistics numbers; however, based on existing literature, primary research concerns pertain to visibly severe on-the-job injuries such as musculoskeletal effects, falls overboard, and deaths. This is despite evidence that microbial hazards such as Vibrio vulnificus and V. parahaemolyticus may present considerable risks to workers. Morbidity and mortality statistics also do not capture the human and societal impacts from injury or consumer illness, writ large, including from microbial hazards that can have long-lasting individual- and community-level impacts due to fisheries closures, product recalls, lawsuits, and insurance claims. Anecdotal evidence suggests that microbial hazards have a wide range of physical, mental, economic, and sociocultural effects on fishermen and fishing communities in the U.S. From a Total Worker Health® (TWH) perspective, this is a lost opportunity, and a disservice to the industry as without empirical substantiation, it is difficult if not impossible to develop and implement effective and efficient interventions and policies that encompass psychosocial, economic, and organizational factors, in addition to physical and microbial hazards. This dissertation provides an overview of how Vibrio and vibriosis are TWH challenges to watermen and seafood processors, by focusing in particular on the Chesapeake Bay region. We provide qualitative context from 28 semi-structured interviews conducted with stakeholders from myriad parts of the industry, showing how negative effects occur to these workers as a result of vibriosis, including in consumers. Then, we provide the framework for developing a quantitative microbial risk assessment on the effectiveness of high hydrostatic pressure as a post-harvest treatment for reducing V. parahaemolyticus concentrations in the two most commonly grown domestic oyster species, Crassostrea virginica, C. gigas. This latter aim is important context for demonstrating a potential intervention that could reduce consumer illness and thus limit effects to watermen and processors

    ANALYSIS AND RECOMMENDATION OF POLICIES TO SUPPORT THE ENERGY TRANSITION OF WEST TEXAS ENERGY COMMUNITIES

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    Declarations of emission reduction goals have left an uncertain future for oil and gas markets. During a transition to increased use of clean energy resources, areas known as energy communities which economically depend on the success of the fossil fuel industry may experience more negative impacts than other areas of the nation. This includes the Permian Basin of West Texas, one of the largest areas of oil and natural gas production in the United States. The following analysis investigates policy solutions which could provide support for the communities in this area and avoid such trends as those seen in coal energy communities which have experienced economic hardship due to a changing energy landscape. For the investigation, review of past policy efforts as well as qualitative data analysis is used to determine a set of policy criteria and two policy alternatives to investigate. The first policy suggests the development of new education and retraining programs through community colleges and vocational schools. A second policy alternative considers support for emerging and developing industries of the area, including wind, solar, geothermal, hydrogen, and aerospace. After contrasting both cases against a “business-as-usual” control scenario, the first policy alternative was determined to be a more likely candidate for success in the area, but certain elements of a policy to develop industry outside the oil and gas energy sector may also be appropriate for policy makers to consider

    RE-ANALYSIS OF DEFINED BACTERIA CONSORTIA’S IMPACT ON IMMUNE CHECKPOINT INHIBITORS RESPONSE IN MURINE MODELS

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    Immune checkpoint inhibitors (ICI) have revolutionized the cancer treatment across all types of tumors, but only 10-30% patients have durable responses. Gut microbiome has shown potential to be a biomarker in predicting tumor responses. Several preclinical and clinical studies have previously identified specific bacterial strains associated with ICI responses. Moreover, some bacterial species have been shown to modulate ICI responses. However, there is little consensus on which bacteria are beneficial or harmful bacteria across all the current studies. Our lab previously conducted a computational re-analysis of five human studies which has suggested potential relationship between specific bacterial strains and ICI responses, and we found new signals that were not seen in the prior studies. To test our computational analysis, we assembled two defined consortia associated with ICI response and nonresponse for further study in our murine tumor models. The initial colonization studies unfortunately had some cross-contamination, but still indicated most of the bacteria in our consortia could successfully colonize in germ-free mice, except Faecalibacterium prausnitzii. Only Akkermansia muciniphila had stable colonization in the response group while most of the nonresponse bacteria can stably colonize in the first two weeks. The nonresponse bacteria also induced B and T cell immune pathways in the distal colon, whereas the response bacteria and uninoculated germ-free mice did not. Finally, murine tumors in mice inoculated with nonresponse bacteria had improved anti-tumor responses to anti-PD-L1 antibody, compared to those inoculated with response bacteria, and had increased myeloid cells infiltration. While this finding contradicts the initial hypothesis and the colonization data for the tumor models is still pending, these findings may lead to additional hypotheses about the effect of A. muciniphila alone and/or the interaction of A. muciniphila with the nonresponse associated bacteria in mediating ICI response

    TWIN-S: A DIGITAL TWIN PARADIGM FOR SKULL BASE SURGERY

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    Digital twins are being used in various industries for design, predictive maintenance, improved operations, risk mitigation, and sustainability. In the field of medicine, digital twins provide a range of benefits to surgeons throughout the entire surgical process, from pre-operative planning to intra-operative guidance and post-operative record- keeping. They help to improve patient outcomes and reduce the risk of complications by enabling greater precision, accuracy, and risk mitigation. This essay introduces Twin-S, a digital twin framework designed to improve surgeons’ situational awareness during skull base surgery. The framework utilizes high-precision optical tracking and real-time simulation to model critical aspects of the surgery, such as surgical tools, patient anatomy, and surgical cameras. The calibration routines used in Twin-S ensure that the virtual representation accurately reflects real-world processes. Twin-S captures the real-world surgical progress and updates the virtual model at a frame rate of 28 with an average error of 1.39 mm during the drilling process. By providing temporally varying augmented Sim-to-Real overlays derived from the continuously updated virtual model, Twin-S offers situational awareness to the surgeon. Future research could concentrate on utilizing vision-based techniques to improve the accuracy of Twin-S. Incorporating additional sensor modalities, such as lidar and robot dynamics would enable Twin-S to model real-world processes more accurately and provide the surgeon with more comprehensive information

    WHAT’S IN THE BOX? EXPLORING MEAL-KIT SERVICES AS A STRATEGY FOR IMPROVING FOOD ACCESS AND MITIGATING DIETARY DISPARITIES

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    Introduction: This research explored the potential of meal-kit services as a tool for improving the dietary habits of US adults and addressing factors known to influence eating behaviors. Using national survey data and information from pilot study of a community-led meal-kit service called SouthEats, we explored associations between the use of meal-kit services and reported dietary intake both nationally and locally, and evaluate the acceptability, adoption, and feasibility of meal-kit services among low and middle -income households in Washington DC. Methods: Secondary analyses of national survey data, were conducted using bivariate and multivariate regression models to identify differences in demographic characteristics and reported dietary behaviors between new and never meal-kit users. This was complemented by examination of administrative records, worker interviews, and pilot study data from a longitudinal SouthEats customer survey. This information was collected during the COVID-19 pandemic. Results: The national data indicated that compared to never users, new users of meal-kit services reported eating more fruits and vegetables (PR: 1.95, 95% CI: 1.42, 2.68), and more red and processed meats (PR: 2.39, 95% CI:1.49-3.85) since the pandemic began. Results from the SouthEats feasibility and pilot study suggest that the meal-kit service was acceptable among people living in low food access areas who may also be low-income. Among SouthEats customers who completed the pilot study there was a significant decrease in the median amount of time spent on meal preparation between baseline and midpoint. In the pilot study, participants’ reported vegetable consumption increased between baseline and midpoint but then decreased between the midpoint and endpoint survey periods. However, there were no statistically significant changes in the outcomes of home eating behaviors, perceptions of neighborhood healthy food access, vegetable self-efficacy, or vegetable consumption among pilot study participants. Conclusion: This research provides preliminary information that meal-kit services may have the potential to increase vegetable consumption. Low-income household have an interest in using meal-kits, and community-based meal-kit models are likely more acceptable among low- and middle-income adults living in areas with low access to healthy food. Meal-kit services may provide an intermediate solution to improving the frequency of home cooking and dietary behaviors

    ENGINEERING BIOMIMETIC TUMOR MICROENVIRONMENTS WITH CONTROLLABLE STROMAL TOPOGRAPHY FOR STUDYING CANCER CELL DISSEMINATION

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    Metastasis resulting from unrestrained dissemination of cancer cells is the primary cause of cancer death. Disseminated cancer cells, especially multicellular clusters, are distinct from their main tumor in various respects to adapt survival advantages during metastasis. Moreover, multicellular clustering allows cancer cells to invade collectively and remodel surrounding extracellular matrix fibers. The remodeled stromal topography characterized by radially aligned fibers predicts unfavorable prognosis and cancer relapse. However, whether and how the aligned topography promotes cancer cell clusters detaching from their main tumor and provides them survival advantages against challenging microenvironments remain incompletely understood. Furthermore, a biomimetic cancer cell cluster dissemination model to recapitulate tumor behavior responding to stromal structures is critically lacking. This thesis takes advantage of multidisciplinary technologies from biomimetic tumor modeling, transcriptome profiling, survival analysis, to high-throughput drug screening to comprehensively unveil how stromal topography facilitates cancer progression. First, we decouple stromal topography from other tumor microenvironmental cues by developing 3D and quasi-3D models recapitulating the topographical transition from tumor center to the invasive front with aligned topography. Our models reveal that aligned topography promotes breast cancer cell dissemination as multicellular clusters. Then the transcriptome profile of topography-induced disseminated clusters isolated from our model identifies upregulated aryl hydrocarbon receptor (AhR) / cytochrome P450 family 1 (CYP1) drug metabolism pathway. On a high throughput topographical platform, the drug response profiles of cancer cell clusters to FDA-approved oncology drugs functionally determine that aligned topography promotes chemoresistance of cancer cell clusters. Finally, blocking the antioxidant function of the AhR/CYP1 pathway enhanced by aligned topography sensitizes cancer cell clusters to chemotherapy, suggesting the potential clinical application of this study. Overall, this thesis advances the technology of biomimetic tumor modeling by recapitulating topography-induced cancer cell cluster dissemination. Furthermore, by indicating a new concept of inhibiting stromal topography upregulated signaling to reverse the chemoresistance of disseminated cancer cell clusters, we provide evidence favor targeting stroma-induced survival advantages of cancer cells as a promising therapeutic strategy

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