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    Other Duties as Assigned: Turnover and Turnover Intentions among Early Career Undergraduate Admissions Officers at Selective Higher Education Institutions

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    Undergraduate admissions offices are tasked with recruiting, admitting, and yielding students for their respective institutions, a process that impacts the current student body and ultimately, the alumni of a given school. At selective undergraduate institutions, job responsibilities for admissions officers can include traveling to meet prospective students, reading thousands of applications, and hosting on-campus events throughout each year. However, these components of the role, along with the relatively low compensation and long work hours, lead to admissions jobs anecdotally being considered as having high levels of turnover among early career staff relative to other functional areas in higher education. Such turnover leads not only to financial costs for a college, but also to the loss of institutional experience, as well as the potential for emotional exhaustion for other employees. This qualitative research study explored the phenomenon of admissions turnover from the perspectives of 20 current and 15 former early career admissions officers from selective higher education institutions, looking to identify and explore the factors that contribute to turnover or turnover intentions among such professionals. The study revealed factors that concentrated around themes of connection and community, as well as advancement and professional development, with both current and former admissions professionals highlighting many intersectional factors. These factors included the critical role of supervisors, access to onboarding training and ongoing professional development, compensation and advancement opportunities, and work-life balance. Given these findings, admissions leaders are encouraged to consider creating intentional onboarding and training pathways for early career admissions officers, fostering strong organizational community to encourage connection to admissions work, and establishing intentional supervisory structures to promote support networks and provide ongoing feedback for staff. Other recommendations include reevaluating compensation structures within a set of roles and an office, designing ongoing professional development opportunities within and beyond the admissions office for all staff, and highlighting clear organizational policies around advancement pipelines

    Does Administration Timing of Ondansetron, a 5-HT3 Receptor Antagonist, Affect Inhibition of the Bezold-Jarisch Reflex in OB C-section Patients Receiving Spinal Anesthesia

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    Ondansetron (a 5HT-3 receptor antagonist) has been shown in multiple randomized controlled trials (RCT’s) and meta-analysis to inhibit activation of Bezold-Jarisch Reflex (BJR) in response to spinal anesthesia for elective cesarean section patients. Studies have not determined whether the timing of administration changes the inhibitory affect of ondansetron in this patient population. This project addressed the following question: Does administration timing of Ondansetron, a 5-HT3 receptor antagonist, affect inhibition of the Bezold-Jarisch Reflex in obstetric cesarean section patients receiving spinal anesthesia? De-identified aggregated electronic medical record data for a one-year period was obtained. Data was grouped by ondansetron administration timing prior to spinal administration: ≤ 15 minutes (G1), \u3e 15 minutes and ≤ 30 minutes (G2), \u3e 30 minutes (G3). Blood Pressure (BP) data, including systolic, diastolic and mean arterial pressure (MAP), was included for four time points: pre spinal, 5-, 15- and 30-minutes post spinal. Change in BP from baseline were used for analysis. Total vasopressor usage was also included for analysis. Sixty-six obstetric cases were included, (G1 n=24), (G2 n=24) and (G3 n=18). Data was analyzed using the one-way ANOVA test for BP change scores and the Kruskal-Wallis for evaluating vasopressor use. No statistical significance between groups was found in BP change scores or vasopressor use. However, G3 did show greater drops in BP and increased vasopressor usage compared to G2 and G1. Further evaluation is recommended through either a large-scale retrospective study or randomized control trial (RCT)

    Advance Directives and the ESRD Patient: Why are They Missing?

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    Standardizing Handoff: From Operating Room to Intensive Care Unit

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    The transfer of patient information that is shared among health care providers during transitions of care is an integral component of the handoff process that ensures patient safety and continuity of care. The postoperative period is one of high acuity. Communication failures during the acute phase of transfer from operating room to intensive care unit leave critically ill patients vulnerable to devastating adverse outcomes. The problem identified in the Surgical Intensive Care Unit (SICU) of a North Philadelphia hospital is a lack of standardization with postoperative patient handoffs. The purpose of this project is to assess the impact of utilizing a standardized postoperative handoff tool and to evaluate the satisfaction of SICU nurses through a Plan Do Study Act (PDSA) methodology of quality improvement (QI)

    Scalable Machine Learning Methods for the Analysis of Single-Cell Transcriptomics and Multiomics Data

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    Transcriptomics and proteomics-based expression profiling technologies have become increasingly popular, more affordable, and more accurate in recent years. Expression profiling of expression at the single-cell resolution allows investigators to identify rare cell subtypes in human tissue which would be otherwise confounded in lower-resolution, bulk sequencing technologies. Previously, investigators studied human cell populations by profiling RNA expression in single cells using single-cell RNA sequencing (scRNA-seq) technologies. More recently, multi-modality sequencing technologies such as Cellular Indexing of Transcriptomes and Epitopes by Sequencing (CITE-seq) have emerged, which allow investigators to profile multiple forms of biological expression (in this case RNA and protein expression) simultaneously in the same cells. Investigators can study human biology now with greater detail than ever before, but challenges remain. (1) Cell subpopulations are not always neatly separated from one another, which makes cell type classification difficult. (2) Technical batch effects also often plague scRNA-seq studies and confound real biological signals. (3) Multi-modality technologies are excellent but remain expensive to do at scale. In this work, we seek to address these various challenges and difficulties associated with scRNA-seq and CITE-seq analyses. To address challenge (1), we propose a smooth pseudotemporal modeling approach which characterizes a cell’s identity as a mixture of two discrete identities, allowing for a continuous sliding-scale cell type rather than requiring cells to separate into discrete types. To address challenge (2), we propose an augmented autoencoder which uses a self-supervised Kullback–Leibler divergence, along with a specialized branching architecture to correct for batch effects in the full gene expression feature space. Lastly, to address challenge (3), we develop a hybrid feedforward-recurrent neural network approach which supports protein prediction, imputation, embedding, uncertainty quantification, and cell type label transfer, allowing the user to use reference CITE-seq datasets to predict and study protein expression in larger single modality RNA-only data. We validate the utility of each of our approaches using real datasets with gold standard true expression and experimentally validated cell type labels. We also demonstrate real use cases for our methods, such as improving downstream pseudotime analyses using batch correction and identifying immune response biomarkers to an H1N1 vaccine

    Developmental Role of H19 and IGF2 in Mouse and Human

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    Genomic imprinting is a mammalian-specific phenomenon where gene expression is regulated differently between maternally- or paternally-inherited alleles. As most imprinted genes are important growth regulators, proper expression of these genes is crucial for normal development in humans and mice. A well-known H19/IGF2 imprinted cluster harbors two growth regulators with opposite functions, H19 and IGF2. The maternally expressed H19 gene is a long noncoding RNA implicated in growth suppression, while the paternally expressed IGF2 gene is a major growth factor in multiple developmental pathways. Dysregulation of the imprinted H19/IGF2 cluster is associated with Beckwith-Wiedemann Syndrome (BWS) and Silver-Russel Syndrome (SRS). Although both are primarily represented by abnormal growth, BWS and SRS show substantial variability in the severity of symptoms among patients. The mechanism underlying how the dysregulated H19/IGF2 expression leads to a specific pathological defect is still unknown. BWS and SRS phenotypes have been largely attributed to aberrant IGF2 expression because the exact role of H19 has been difficult to discern due to its coupled regulation with IGF2. Additionally, because of the mosaic nature of the epimutations in human patients, it has been challenging to understand the contribution of abnormally expressed H19 and IGF2 to the tissue-specific BWS/SRS pathologies. To dissect the effect of H19/IGF2 dysregulation in various lineages, we utilized two model systems. In chapter 2, we present the human induced pluripotent stem cells (hiPSCs) that are derived from BWS patient fibroblasts with paternal uniparental disomy of chromosome 11 (pUPD11). Our iPSC clones maintained proper imprinting in H19/IGF2 locus with an expected epigenetic profile of pUPD11. Differentiation of hiPSCs into a hepatic lineage enabled us to examine the effect of pUPD11 in a tissue type that is prone to BWS-related tumors. Through the transcriptomic profiling of pUPD11 and non-pUPD11 hepatocytes, we could identify the target pathways that are affected by pUPD11 and likely contributing to the increased occurrence of hepatoblastoma and growth anomalies in BWS. In chapter 3, we utilized mouse models with subtle perturbations of H19 and Igf2 expression to address the independent roles of H19 and Igf2 in SRS-like pathologies. We started with a previously described humanized mouse model that substituted the human H19 imprinting control region for the corresponding mouse region (H19+/hIC1), which exhibited H19 overexpression and Igf2 depletion. These mice had severe developmental defects in the heart and placenta, which may significantly contribute to the previously described perinatal lethality and severe growth restriction. While normalizing H19 expression was not sufficient for the full rescue of the growth restriction and lethality, altering both H19 and Igf2 expression restored viability, although certain cardiac defects were still retained. Our results demonstrate that physiological levels of H19 and Igf2 are crucial for normal cardiac and placental development. Overall, this work emphasizes the importance of precise regulation of H19 and IGF2 expression in embryonic growth and tissue formation. These results enhance our understanding of how molecular defects in the H19/IGF2 cluster lead to the characteristic BWS and SRS phenotypes, further helping to establish molecular subtype-specific therapeutic strategies

    VIP Interneuron Cell and Circuit Dysfunction Underlying Dravet Syndrome

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    GABAergic inhibitory interneurons of the cerebral cortex expressing vasoactive intestinal peptide (VIP-INs) are rapidly emerging as important regulators of network dynamics and normal circuit development. Several recent studies have also identified VIP-IN dysfunction in models of genetically determined neurodevelopmental disorders (NDDs). In this dissertation, we review the known circuit functions of VIP-INs and how they may relate to accumulating evidence implicating VIP-IN dysfunction in the mechanisms of prominent NDDs. We highlight recurring VIP-IN mediated circuit motifs that are shared across cerebral cortical areas, and how VIP-IN activity can shape sensory input, development, and behavior. Ultimately, we extract a set of themes that inform our understanding of how VIP-INs influence pathogenesis of NDDs. We focus on a particularly enticing disease candidate: Dravet Syndrome, a severe NDD characterized by epilepsy, autism spectrum disorder (ASD), and intellectual disability (ID) caused by loss of function variants in SCN1A which codes for the voltage-gated Na+ channel α subunit, Nav1.1. We go on to show that Nav1.1 is expressed in VIP-INs, and loss of a single copy causes VIP-INs to be hypoexcitable in acute brain slices from Scn1a+/- mice. Using this same model, we show that this intrinsic hypoexcitability translates to decreased VIP-IN activity and impaired cortical network dynamics in vivo using two-photon calcium imaging. We find that the above results are replicated when using a conditional deletion of Scn1a in VIP-INs. However, these conditional mutants do not have epilepsy like the global model, but do replicate core features of ASD and ID. This dissociates the roles of VIP-IN dysfunction from potential involvement of other cell types in Dravet pathogenesis. Finally, using publicly available single cell RNA sequencing (scRNA-seq) data from the Allen Institute, we also identify several underexplored disease-associated genes that are highly expressed in VIP-INs. We survey these genes and their shared related disease phenotypes that may broadly implicate VIP-INs in ASD and ID rather than epilepsy. We conclude with a discussion of the relevance of cell type-specific investigations to drive the potential development of therapeutics targeting VIP-INs in the age of genomic diagnosis and precision medicine

    A New Era in the Fight for Nursing Civil Rights: Mercy-Douglass Hospital School of Nursing

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    The mid-twentieth century marked a critical turning point in the history of race and American nursing. The political strategies traditionally employed by Black Americans for racial advancement and health improvement, particularly self-help and racial solidarity, gave way to new demands for equal citizenship rights. Black nurses were pioneers in the fight for racial equality in healthcare, battling interlocking racial, gender, and class oppression. Their quest for inclusion and equal opportunity intensified during World War II and culminated in their integration into the American Nurses Association in 1948, and the subsequent dissolution of their separate professional organization, the National Association of Colored Graduate Nurses, three years later. Yet, little is known about the professional development of Black nurses during the classical civil rights era. Using oral history and archival methodologies, this study draws on the experiences of women who trained and worked at Mercy-Douglass Hospital School of Nursing in Philadelphia, Pennsylvania to address this gaping silence in the literature. Established in 1948, Mercy-Douglass provided vital medical services to the city’s expanding Black population, and was a key site for the training, employment, and leadership development of Black nurses and doctors who were barred from white institutions. The study’s findings revealed that Black nurses’ struggle for racial equality was more complicated than simply being integrated into the mainstream of nursing. It also entailed a battle to safeguard and integrate their own educational and medical institutions. In the end, Black-run nursing schools like Mercy-Douglass acted as a life vest during the turbulent period of desegregation, keeping the professional Black nursing class afloat until the system of legalized racial segregation and inequality was dismantled. This research has important implications for understanding the persistence of racism in nursing education, research, and practice in the United States, as well as strategies for combating it

    Rheology of Marine Sponges and Magnetoviscoelastic Solids

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    Most everyone has heard of a marine sponge, probably not many have heard of a magnetoviscoelastic solid. Both are complex materials in the sense that they are heterogeneous and responsive to stimuli like applied flows and fields. The natural way to describe these materials is rheology: the study of how things deform and flow and how those macroscopic, mechanically responsive properties can be attributed to mesoscopic and microscopic processes. In the case of sponges, those processes are likely biologically important (not to mention fascinating), and thus the goal of Ch. 2–3 of this thesis is to construct the beginnings of a rheological picture of living sponges. Ch. 1 provides relevant biological information about the pore bearers and also theoretical physics background. Ch. 2 asks the question of what elastic properties do sponges of different growth form shave. Small uniaxial deformation experiments on a set of common species of spherical, cylindrical, and more disordered growth forms, are presented. Sponge tissue mechanics are shown to be diverse, particularly in the behavior of the shear modulus as a function of applied compression. Correlations between degree of tissue anisotropy and growth morphology are discussed from which are drawn broad, physiologically relevant conclusions about sponges. Ch. 3 asks if it can be shown that sponges are somehow tuned to the local hydrodynamics of their environment, leading to the high plasticity observed as no two sponges are alike. A natural experimental extension of Ch. 2 is to make the deformations time-dependent. If sponge tissue mechanics are highly time-dependent, this immediately suggests tuning, or a memory of recent straining. Oscillatory shear strains of different frequencies at both small and larger amplitudes are made on the same set of sponges as in Ch. 2. Further diversity is uncovered and conclusions made about the dynamical properties of sponges – particularly those of more disordered growth forms and tissue microstructures and their potential to tune to local flow. Ch. 2–3 resulted in the manuscript “rheology of marine sponges reveals diverse dynamics and anisotropic mechanics.” Ch. 4 is a short chapter born from years of thinking about sponges as a physicist. A simple phenomenological transport view of passive flow in sponges is presented and back-of-the-envelope estimates of hydraulic properties of some sponges made. Implications of this non-equilibrium steady state description of flow in sponges are explored. In the case of magnetoviscoelastic solids, the magic of the magnetic field is utilized for new substrates in mechanobiology. The goal of Ch. 5–6 of this thesis is to outline novel techniques for magnetically controlling the mechanics of substrates populated with cells– ultimately for learning about 3D cellular mechanotransduction. These chapters are the result of collaborations in the Center for Engineering Mechanobiology at U Penn, the BiofluidMechanics Laboratory at Rowan University, and the Laboratory of Magnetic Soft Materials at the University of Latvia. The magnetic-field induced stiffening effect in carbonyl iron microparticle embedded polydimethylsiloxane (PDMS) based elastomers is characterized in Ch. 5 and the tunability of these ultrasoft substrates for applications in mechanobiology are explored. Collaborators for this chapter include Andy Clark (Ph.D. candidate, Physicsat Bryn Mawr College) and Alex Bennett (Bioengineering postdoc, U Penn), and the other coauthors on the published work: (Clark et al., 2021). Ch. 6 extends the general field-stiffening effect of magnetic microparticles embedded in a polymer network to the more physiologically relevant collagen and fibrin based hydrogels. The main part of this work was done by Kiet Tran (Ph.D. candidate, Biomedical Engineering at Rowan University): the confirmation of rapid cellular response to three-dimensional changes in substrate mechanics affected by an applied magnetic field (Tran et al., 2021). Andrejs Cebers (Professor, Theoretical Physics, University of Latvia) constructed and I communicated and validated a continuum magnetoelastic stiffening model with the data for both the biopolymer gels as well as the PDMS-based elastomer of Ch. 5. Ch. 7 is an extremely short, poetic conclusion to the science presented. Rheology is a natural bridge between biology and physics. Complex materials, such as living marine sponges and cellularized magnetoviscoelastic solids are here powerfully probed by a rheometer. The contributions presented in this thesis push the boundaries of how to describe biological materials and their behaviors with physics

    The Role of Morphological Structure in Phonetic Variation

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    This dissertation is situated in broad debates about the architecture of the phonological grammar, and the sensitivity of gradient phonetic parameters to morphological structure. It takes, as its primary case study, a linguistic variable that is of prevailing interest to sociolinguists and phonologists alike: English Coronal Stop Deletion (old~ol\u27; CSD). While CSD is robustly sensitive to the morphological class of words in which coronal stops are contained, its alignment with the small class of other morphology--phonetics interactions is not straightforward. I approach this problem from several angles, incorporating diverse methodologies. In the first place, I provide new articulatory evidence suggesting that CSD does indeed have its primary locus in the gradient phonetics, demonstrating that the magnitude of tongue tip raising to a coronal stop constriction is gradiently conditioned by morphology. Moreover, this variation is typologically distinct from the majority of other examples of phonetic phenomena conditioned by morphology, which primarily concern durational parameters. In the rest of the dissertation, I problematise CSD\u27s status as exceptional in this way, probing how well explanations for other morphology-sensitive phonetic phenomena (i.e. effects of prosody and word predictability) account for CSD patterns. In two perception experiments, listeners do not show perceptual sensitivity to the covert tongue tip raising observed in articulation, but do reflect an association between morphological complexity and increased duration. Finally, a large-scale corpus study shows only measures of word frequency that are relative to a word’s larger morphological paradigm predict CSD patterns accurately. This suggests that morphological structure was a key missing element in predictability accounts of the variable. Ultimately, surface CSD may amount to the confluence of more than one type of morphologically conditioned phonetic phenomenon. This dissertation sets the stage for continued progress towards an account integrating these different factors, and generates new puzzles in the asymmetry between production and perception for variable phonology and phonetics

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