American Society for Eighteenth-Century Studies

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    Non-legged locomotion on complex 3-D terrain and wet flowable substrates

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    Animals can traverse any complex 3-D terrain and substrate by modifying their primary locomotion strategy or transitioning to other strategies. Robots, unlike animals, often struggle to traverse similar environments due to lack of understanding of robot obstacle/substrate interaction to generate propulsion. Understanding this interaction will help develop control strategies for robots to locomote similarly to animals. Snake and amphibious fish locomotion are excellent for traversing complex 3-D terrains and wet flowable substrates respectively. Snakes can successfully traverse such terrains via 3-D body bending to generate the right propulsion. Snake robots still struggle to traverse such terrains due to lack of understanding in controlling 3-D body bending to push against obstacles to generate and control propulsion. Previous studies show that generalist snakes likely sense body-terrain contact forces via tactile sensing to adjust body bending in real-time. We took the robophysics approach to understand snake locomotion on complex 3-D terrain due to lack of knowledge of tactile sensing. We developed a sensorized snake robot capable of 3-D body bending and tactile sensing. We allowed this robot to traverse an obstacle using vertical bending and showed that it is useful for systematic studies due to high repeatability. Despite challenges in traversing wet flowable substrates due to variable wetness, amphibious fishes can easily adapt to such variations via body and fin adjustments with substrate interaction. To understand how locomotor morphology, control, and kinematics permit performance, quantification of locomotor-substrate interaction and how propulsive forces are generated are necessary. Despite several studies on dry, wet, and saturated sand, only few animal studies focused on mud with no study in interaction mechanics yet. We developed tools and methods to prepare, control, and maintain mud with different strengths similar to sand. We performed systematic studies of mudskipper and ropefish, and a preliminary study of bichir moving on different mud strengths with each animal representing a distinct strategy used by amphibious fishes on land. All three fishes had more sinkage and contact length as mud weakened. Mudskipper used its tail to propel against weaker mud. Bichir and ropefish vertically lifted some body sections likely to reduce drag on stronger mud

    Characterizing Well-being in Families Affected by Pediatric Genetic Conditions

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    Background: Family well-being is a multifaceted construct encompassing various dimensions, including but not limited to emotional, social, financial, and physiological aspects. Understanding these domains is crucial for measuring the effects of interventions on family-centered outcomes and developing targeted interventions and support services tailored to the unique needs of families with a child or children affected by genetic conditions. This study aims to identify and organize domains of family well-being important to family members of children with genetic conditions. Methods: The research consists of a scoping review and narrative synthesis of qualitative studies to explore dimensions of family well-being specific to families with children affected by genetic conditions. The scoping review was conducted following the framework developed by Arksey and O’Malley.1 A conceptual model of family well-being in this context was designed through analysis of the data extracted from the scoping review. Results: The scoping review identified 53 articles assessing elements of family well-being in parents, caregivers, and/or siblings of children with a genetic condition. Thematic analysis of these articles yielded the development of four primary domains of family well-being, those domains being Emotional, Physical, Social, and Financial. Specific to families with children with genetic conditions, this review identified sub-domains including Health Service Quality, Awareness and Stigma, Child Autonomy, and more as relevant sub-domains. Discussion: In the context of families with children with genetic conditions, domains and sub-domains of family well-being emerge as nuanced and interconnected concepts. The identified domains and sub-domains underscore the complex interplay of factors impacting these families. This research lays the groundwork for further exploration into how these domains can be effectively measured, including the identification and development of appropriate tools to assess these latent concepts. Understanding these domains can aid in the design of targeted interventions and support services that address the unique challenges faced by families navigating genetic conditions and also advance understanding of how genetic medicine interventions impact family well-being. Future research should focus on validating these domains across diverse populations and investigating their relative importance for the well-being of families

    Enhancing Guidewire Coupling in Balloon Catheters

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    This paper explores enhancements to the PUMA-G System, a proprietary medical device by CoapTech®, designed for the efficient placement of enteral nutrition feeding tubes (G-tubes). Central to this procedure is the mechanical coupling of a percutaneous guidewire (PGW) with an internal balloon catheter (IBC). Despite thousands of successful implementations, inconsistencies from the internal decoupling of the PGW and IBC necessitate improvements, particularly to accommodate obese patients. A detailed analysis of the PUMA-G procedure highlights unique challenges in using guidewires, emphasizing metrics such as trackability and coupling strength. The study investigates the effects of obesity on guidewire performance, noting increased tissue resistance and anatomical complexity in larger patients. Existing guidewire technologies, while advanced, lack the specific requirements for PUMA-G, necessitating novel solutions. This research proposes integrating a cannula to reduce friction in adipose tissue while exploring new PGW designs and a novel balloon-snare catheter to enhance coupling strength. Methodological rigor is maintained through standardized testing of needle/cannula configurations and PGW variants, focusing on compatibility and procedural efficacy. The findings suggest that a cannula could significantly reduce frictional forces while maintaining compatibility with current product safety requirements, thus enhancing trackability. The redesigned PGW tips and balloon-snare prototype exhibit improved coupling strength. These innovations promise to mitigate complications, ensuring safer and more reliable PUMA-G procedures, particularly in obese patients. Future work will focus on further optimization and validation of these enhancements

    Cells in the Polyaneuploid Cancer Cell State are Pro-Metastatic

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    Emerging evidence has implicated a role of the Polyaneuploid Cancer Cell (PACC) state in cancer progression. PACCs are enlarged endocycling cells with increased genomic content that arise in response to stress. Our correlative study of patients with prostate cancer revealed that PACC presence was predictive of future metastasis. Ergo, we hypothesized that PACCs are pro-metastatic. Though research has delineated the steps of the metastatic cascade, the determinants of bone-specific metastasis have remained elusive. Applying critical concepts from foraging theory and movement ecology, we hypothesized that organotropism results from habitat selection by foraging cancer cells. Specifically, we posited that cancer cells only perform habitat selection when employing reversible motile foraging strategies. Importantly, our framework emphasized the importance of testing chemotaxis when studying metastasis. Upon in vitro investigation, we found PACCs exhibit increased capacity for environment-sensing and directional migration in chemotactic environments. These data indicate that PACCs are chemotactic and thus have increased metastatic potential, making them worthy of further in vivo analysis. Rigorous evaluation of in vivo metastasis models requires rapid and reliable circulating tumor cell (CTC) and disseminated tumor cell (DTC) detection. We developed a flow cytometry-based method that enables swift and simultaneous comparison of CTCs and DTCs from single animals, enabling evaluation of multiple metastatic steps within one model system. This approach is reproducible, high-throughput, broadly applicable and highly adaptable to a range of scientific inquiries. Most important for the present work, it enables the recovery and PACC-state analysis of CTCs and DTCs, allowing for a rapid first look at the comparative metastatic competency of PACCs vs. nonPACCs. We used our technique to query the metastatic competency of PACCs in vivo. Across all models, the majority of CTCs and DTCs were in the PACC state. Additionally, in vivo colonization assays proved PACC populations can regain proliferative capacity at metastatic sites following dormancy. An exploratory return to in vitro mechanistic experimentation revealed a PACC-specific partial-Epithelial-to-Mesenchymal-Transition phenotype, a phenotype that supports our hypothesized reversible motile foraging framework. Altogether, our data point to a causative relationship between PACCs and increased metastatic risk, revealing a new approach through which to target metastatic disease

    Emergent, decaying, and spinning nematic order in collective motion of active semiflexible filaments

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    Spontaneous ordered collective motions frequently emerge in systems composed of numerous interacting active units, from animal flocks, cellular tissues, and bacterial colonies to self-propelled colloids. These active matter systems provide new opportunities to study nonequilibrium physics as they are constantly driven by energy input, leading to unique and often surprising behaviors. The complexity of active phases becomes especially pronounced when the active components possess sufficient shape anisotropy to form liquid crystalline order, resulting in active nematic behaviors. Gliding assay in vitro experiments have provided a test bed to study the collective motions of biological cytoskeletal filaments like actin and microtubules and unlocked diverse collective active phases, including states with dynamic lanes and long-ranged orientational (LRO) order. Recent gliding assay experiments with mobile motors have reported spatial motor restructuring where the concentration of motors becomes enriched below the microtubule lanes that they drive, leading to a case of non-uniform motor distribution. Using Brownian dynamics, we simulate the collective motion of self-propelled semiflexible filaments in order to gain insights into the aligning mechanisms at work in these gliding assay systems. We find that a microtubule lane decorrelates in its position and becomes more dynamic in the presence of non-uniform activity arising from a non-uniform motor distribution. We also find that, without aligning torques in the microscopic model, LRO order can only be achieved when the filaments are able to overlap. Our model predicts that a LRO active nematic state is merely transient, whereas LRO polar order is the only active dynamical steady state in systems with finite filament rigidity. Chirality is also an important complication of the microtubule gliding assay system. Multiple research groups have reported a consistent counterclockwise rotation of the LRO nematic director. Understanding how this global rotation arises from the molecular-scale chirality of microtubules is deemed crucial for comprehending left-right symmetry breaking and cortical chiral flows during embryonic development and morphogenesis. We demonstrate with the introduction of chiral activity, even in the absence of shape chirality, can produce a coherently rotating active nematic director. Chiral activity is also seen to significantly affect the interplay of polar and nematic symmetries in the LRO steady state. In general, study of these nonequilibrium systems allows us to understand complex systems and their emergent order at the collective level as arising from interactions at the individual level

    Essays on Higher Education and Labor Markets

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    Higher education in the United States is highly differentiated across institutions, degrees, credentials, and educational experiences. In this dissertation, I explore returns to different post-secondary investments, how students from diverse backgrounds sort into them, and what kind of students accrue these returns. In the first essay, I examine the impact of state-mandated remedial placement policies on community college students. I collected data on state remedial policies and combined it with transcript data to assess the effects of the policies on students. I find that state-mandated remedial placement policies increased the number of remediated students without affecting community college enrollment. Students’ grades increase after the policy, increasing their chances of transferring to four-year colleges and attaining bachelor’s degrees. In the second essay, co-authored with Bledi Taska, we analyze the effects of large plant openings on higher education enrollment decisions utilizing the universe of online vacancies in the United States. We find that recent high school graduates take available jobs and move away from college enrollment upon plant openings. However, when the share of jobs requiring two-year college credentials increases, more high school graduates are attracted to two- year colleges, indicating that the type of labor market shocks is relevant in understanding college enrollment decisions. In the third essay, I investigate the impact of college loans on post-college occupational decisions. I do not find any effect of additional college loans on occupational decisions indicating that college students are not credit- constrained or debt-averse. White students with higher debt take jobs with lower hourly wages by entering into occupations requiring less interpersonal skills, and racial differences in social capital can explain this result

    Healthcare Behaviors in Secondary Findings Recipients: A Qualitative Study

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    As more individuals receive broad genetic testing as access and technology improves, more individuals are receiving secondary findings (SFs), or genetic variants of medical value unrelated to the primary reason for testing (Katz et al., 2020). The principle justification for disclosing SFs to patients is the medical actionability of these variants (Green et al., 2013). However, the limited literature that exists suggests a significant portion of SF recipients are not adherent to recommended medical actions associated with their result (Sapp et al., 2021). The determinants of adherence in this population remain unexplored. Through a secondary analysis of semi-structured interviews from participants in the Genomic Services Research Program (GSRP) at NHGRI, this research project begins to address the gaps noted above by examining individuals’ experiences considering and accessing care after receiving a SF. Analysis focused on SFs associated with Lynch syndrome (LS) and BRCA1/2-hereditary breast and ovarian cancer (HBOC), as these cancer predisposition syndromes have been flagged by the CDC as candidates with the greatest potential to improve public health if included in future genomic population screening efforts. Twenty-six interviews were selected from LS and HBOC SF recipients, maximizing time spent engaging with recommendations and demographic diversity. Barriers and facilitators to adherence were identified and mapped onto existing behavior change and implementation science frameworks to yield potential interventions to increase adherence. Interviews were analyzed thematically until saturation was reached. SF recipients are a heterogeneous population, receiving results from a mixture of pathways and with variable personal and family histories of cancer or other illness. Overall, personal and family health histories informed SF recipients’ acceptance of health risk as well as their preparedness and rationale for healthcare action, but rarely featured in their experience with genetic counseling for their result. Pathway to receiving the SF and strength of existing care networks informed participants’ experiences and ease seeking care for the secondary finding. Adherence remained vulnerable to challenges and change over time. Greater use of family history in SF counseling as well as enhanced and active referral and follow-up plans are needed to overcome barriers to fulfilling the promise of SFs

    Navigating Medical Interdependence as a Young Adult with Neurofibromatosis Type 1: Parent and Young Adult Perspectives

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    Transitioning from pediatric to adult healthcare represents a prominent care management challenge for people with childhood-onset conditions, such as Neurofibromatosis Type 1 (NF1). Much of the research into pediatric to adult care transition has traditionally focused on the needs of young adults (ages 18 to 21) to prevent discontinuation of care. Efforts have been made to understand the needs of young adults with NF1 undergoing this transition, leading to the development of clear guidelines and recommendations. However, this guidance does not extend beyond initial adult care transition and does not clearly address the roles of parents in helping young adults manage their health beyond this initial transition. Semi-structured qualitative interviews were conducted with young adults diagnosed with NF1 in childhood, now aged 23- to 33-years-old, and their respective parents. A total of 15 young adults and 14 parents, representing 13 pairs of young adults and parents, were purposively selected and interviewed separately. Thematic analyses across parent and young adult datasets highlight how parents provide logistic, financial, and decisional support for young adults as they move toward independence. Parents’ support extends into interdependent care relationships where parents provide varying degrees of support in accessing care, engaging in care, influencing decision-making, and providing informal support. These care relationships, shaped by individual parent and young adult motivations, exist on a spectrum of interdependence. Familial interdependence in managing care represents what can be considered a ‘secondary care transition,’ where clinicians may need to balance fostering independence and incorporating familial roles

    DEVELOPMENT OF A 3D SIMULATION TOOL LEVERAGING GENETIC ALGORITHMS FOR NEURAL NETWORK OPTIMIZATION IN AUTOMATED DRIVING SYSTEMS: AN APPLICATION FOR SCENARIO ANALYSIS

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    As vehicular automation progresses, designing and validating reliable yet proficient automated driving systems (ADS) remains a challenging imperative, as the current state relies on live driving scenarios and datasets. This research centers on advancing ADS capabilities by proposing a simulation framework and software tool for machine learning consisting of a genetic algorithm (GA) with selection methods and artificial neural network (ANN) architectures all configurable via a user interface (UI), which guides the training and optimization of ANNs, allowing ADS policies to learn and evolve rather than relying on existing datasets. The Unity game engine provides the development environment for crafting the UI to configure driving agents, and for selecting from three different 3D simulation scenario environments of Pasadena, San Diego, and Tampa that are constructed from OpenStreetMap data. The research experiments aim to enhance ADS performance through simulation-based evaluation which aligns with the Intelligent Transportation Systems Joint Program Office (ITS JPO) technical activities, and the National Highway Traffic Safety Administration (NHTSA) vision for safety to accelerate the safe integration of autonomous vehicles into the transportation system. Simulation experiments using different GA and ANN configurations were conducted in each of the 3D scenario environments. Analysis of the simulation results revealed several significant patterns of evolutionary performance of ADS agents across different parameter configurations, yielding varying levels of optimization success across generations in the simulations

    FINDING HOPE IN MIDUS: IDENTIFYING AND EXAMINING THE ROLE OF HOPE IN THE MIDLIFE IN THE UNITED STATES (MIDUS), A NATIONAL LONGITUDINAL STUDY OF HEALTH AND WELLBEING

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    Background: Hope has been associated with health outcomes, but the construct is not usually measured in large health studies. The objective of this dissertation is to construct a proxy measure of hope in a large diverse prospective health study and to investigate associations of hope, depression, and other potential risk and protective factors for depression. Methods: The study utilized data from the Midlife in the United States (MIDUS), a national longitudinal study of health and wellbeing. A hope scale was developed utilizing confirmatory factor analysis (CFA). The hope scale was invariance tested at the configural, metric, and scalar levels. Factor scores from the constructed hope scale were used to examine associations between depression (outcome) and hope (main exposure) controlling for other exposures using multivariable logistic regression. Results: A four-factor hope model consisting of attachment, mastery, survival, and spirituality was developed and the model showed good fit and convergent validity with positive affect, negative affect, and depression in the expected directions. The model was invariance tested and shown to be invariant by sex, age, race, education, and income level. While all four hope factors were not associated with depression in the full analysis or the group specific analyses, hope factors were associated with depression controlling for covariates. Higher levels of spirituality were associated with increased odds of depression in the full sample and in group-specific analysis of females, older adults, Whites, and lower income groups. In African Americans, lower levels of attachment and mastery and higher levels of survival were all associated with higher odds of depression controlling for all covariates. Lower levels of survival were associated with increased odds of depression in Whites controlling for all other covariates. Conclusion: Hope may be protective in some populations and a risk factor in other populations. The result of this dissertation lends support for the inclusion of more nuanced hope measures, like CHS, in large health studies. Further research is needed to determine the temporal and causal relationships between hope and depression with particular emphasis on spirituality in the general population; attachment, mastery, and survival in African Americans; and survival in White Americans

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