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  • 1. Myers, Jessica Contributors to Pathologic Depolarization in Myotonia Congenita

    Doctor of Philosophy (PhD), Wright State University, 2023, Biomedical Sciences PhD

    Myotonia congenita is an inherited skeletal muscle disorder caused by loss-of-function mutation in the CLCN1 gene. This gene encodes the ClC-1 chloride channel, which is almost exclusively expressed in skeletal muscle where it acts to stabilize the resting membrane potential. Loss of this chloride channel leads to skeletal muscle hyperexcitability, resulting in involuntary muscle action potentials (myotonic discharges) seen clinically as muscle stiffness (myotonia). Stiffness affects the limb and facial muscles, though specific muscle involvement can vary between patients. Interestingly, respiratory distress is not part of this disease despite muscles of respiration such as the diaphragm muscle also carrying this mutation. In addition to stiffness, patients experience episodes of transient weakness that remained poorly understood despite years of study. Current treatment focuses on use-dependent block of sodium channels, with off-label use of the antiarrhythmic mexiletine and the antianginal ranolazine. We performed intracellular recordings from muscle of both genetic and pharmacologic mouse models of myotonia congenita to identify the mechanism underlying transient weakness. Our recordings revealed transient depolarizations (plateau potentials) of the membrane potential to –25 to –35 mV in our mouse models. Na+ persistent current (NaP) through Nav1.4 channels is the key trigger of plateau potentials. Inhibition of Nav1.4 with Ranolazine eliminates transient weakness in vivo and prevents the development of plateau potentials. These data suggest that targeting NaP may be an effective v treatment to prevent attacks of transient weakness in myotonia congenita. We also performed intracellular, and ex vivo force recordings on the diaphragm muscle of our myotonic mouse model and found that the diaphragm muscle is immune to myotonic discharges and relatively spared from myotonia. Through comparison with myotonia-affected EDL we propose that some of the resistance of diap (open full item for complete abstract)

    Committee: Mark M. Rich M.D., Ph.D. (Advisor); Eric S. Bennett Ph.D. (Committee Member); Brent D. Foy Ph.D. (Committee Member); Dan R. Halm Ph.D. (Committee Member); Lynn K. Hartzler Ph.D. (Committee Member) Subjects: Biomedical Research
  • 2. Crano, Ricky Posthuman Capital: Neoliberalism, Telematics, and the Project of Self-Control

    Doctor of Philosophy, The Ohio State University, 2014, Comparative Studies

    The goal of this dissertation is to demonstrate some of the ways in which neoliberal social and economic discourse, in particular the work of Friedrich Hayek and Gary Becker, has influenced the cultural evolution of the late-twentieth and early-twenty-first centuries. Chapter One introduces the scope and methods of the project and situates market-oriented social epistemology alongside the development of complexity theory in the physical and information sciences. Chapter Two situates Hayek's philosophies of social science and communication within the broader science cultures of the postwar decades, arguing that his conceptualization of prices and markets is deeply rooted in coterminous projects of cybernetics and general systems theory. Consequently, Hayek's ideas about autonomy, information, and cultural transmission are seen to dovetail with the dominant scientific paradigms and media technologies of the late twentieth century. Chapter Three argues that contemporary financial markets and telematic screen cultures have become operationally analogous in their actualization of neoliberal rationality and social thought. Expanding my reading of neoliberalism beyond Hayek's macrological approach to examine the emerging and all-consuming micrological approach of “human capital” theorists like Becker, this chapter details the ways in which new media platforms, algorithmic cultural practices, and what cultural critics have named the “financialization of daily life” have become primary agents of governmentality today. Chapter Four offers an original interpretation of Michel Foucault's 1979 lectures on neoliberalism, one that reads the abrupt change of course in his research—which, directly following his interrogations of Hayek, Becker, and others, jumped from contemporary political economy to ancient cultures of self-care—as an attempt to locate a genealogical precedent for the subjectivist governmental rationality he had revealed as a dominant theme of neoliberal discourse. (open full item for complete abstract)

    Committee: Brian Rotman (Committee Co-Chair); Philip Armstrong (Committee Co-Chair); Eugene Holland (Committee Member); Kris Paulsen (Committee Member) Subjects: Communication; Comparative; Economic Theory; Philosophy; Philosophy of Science; Social Research; Social Structure; Technology; Web Studies
  • 3. Carlisle, Lemuel Novel Approaches Toward the Synthesis of Bis (2,2,2 trifluroethoxy) Phosphono Esters

    Master of Science in Chemistry, Youngstown State University, 2007, Department of Chemistry

    The aim of this project was the synthesis of several phosphonate esters via reaction of the salt of bis (2,2,2 trifluoroethyl) phosphite and a given alpha halo carbonyl compound in a Michealis-Becker reaction scheme. As an alternative to the use of strong base, we employed cesium carbonate as a mild reagent in hopes of successfully synthesizing our target compounds in high yields.

    Committee: John Jackson (Advisor) Subjects: Chemistry, Organic
  • 4. Khudai, Chandni A Descriptive Study on the Effect of Carrier Status on Mothers' Wellbeing and Adaptation to Duchenne and Becker Muscular Dystrophy

    MS, University of Cincinnati, 2012, Medicine: Genetic Counseling

    Duchenne and Becker muscular dystrophy (DBMD) are progressive and debilitating neuromuscular disorders caused by X-linked recessive mutations in the dystrophin gene. DMD presents in childhood and limits life to the second or third decade. BMD, a relatively milder form, presents in childhood to adulthood. Although improvements in the care of patients with DBMD have enhanced patients' quality and duration of life, there has been no effect on long-term prognosis. Little is known of the psychological morbidity associated with DBMD on families and patients. Birth mothers of children with DBMD, who are themselves carriers of DBMD, may have increased psychological burden. The purpose of this analysis was to describe differences in adaptation and wellbeing between mothers who were carriers and those who were not carriers of DBMD. Data was collected from mothers with biological children with DBMD using a mixed-methods web-based survey. The primary outcome variable, adaptation score, was generated for each participant using the Psychological Adaptation to Illness Scale. Various other scales and investigator-developed questions were also used to measure secondary outcome variables. One hundred twenty-five participants completed the questionnaire and 116 responses were analyzed. Fifty-one (44%) were carriers of a DMD gene mutation, 47 (40%) were not carriers, and 18 (16%) did not know their carrier status. The mean adaptation score was 3.68 (SD=0.9) for carriers and 3.25 (SD=0.9) for non-carriers. Carriers showed better adaptation and higher perceived control than non-carriers (pooled t-test, p=0.02 and p=0.05, respectively). These results were limited by several factors including small sample size, recruitment bias, and increased risk of type 1 error resulting from multiple tests on the data. An open-ended question completed by the carriers revealed various positive and negative effects of being a carrier. In conclusion, carrier status may affect mothers' adaptation to DBMD an (open full item for complete abstract)

    Committee: James Collins PhD (Committee Chair); Kathleen Kinnett MSN (Committee Member); Xue Zhang PhD (Committee Member); Martha Walker (Committee Member) Subjects: Genetics
  • 5. Engels, Andrea W. G. Sebalds Nach der Natur. Ein Elementargedicht.

    PhD, University of Cincinnati, 2009, Arts and Sciences : Germanic Languages and Literature

    „W.G. Sebalds Nach der Natur. Ein Elementargedicht“ bemuht sich, die Missverstandnisse und Verwirrungen, die sich im Laufe der Zeit um das Elementargedicht Nach der Natur in der Sekundarliteratur uber den Text angesammelt haben, aufzulosen. Bis zu dieser Arbeit blieb die Sebald-Forschung dem Gedicht eine genaue Analyse schuldig. In der Einleitung wird nicht nur die kurze Rezeptionsgeschichte des Gedichtes Nach der Natur behandelt, sondern weiterhin auch die Entstehungsgeschichte. Dabei wird die originale Greno-Publikation von 1988 verwendet, die ebenfalls eine Erlauterung der Photographien des Munchener Photographen Thomas Becker beinhaltet. Das Kapitel „Sebalds Grunewald“ bemuht sich, zum einen der Intertextualitat Sebalds in Nach der Natur auf die Spur zukommen und weiterhin eine verstandliche Interpretation der Ergebnisse anzubieten. Es wird dabei deutlich, dass Sebald sich in diesem Abschnitt nicht nur auf die Forschung uber Grunewald vor, sondern auch nach dem Zweiten Weltkrieg stutzt, und sie folglich kontrastiert. Durch diese Vorgehensweise ist es dem Autor moglich, eine nicht nur von unserer Gegenwart entfernte historische Gestalt in Form des Malers des Isenheimer Altares in unsere heutige Realitat zu integrieren. Einer ahnlichen Vorgehensweise wird in dem Kapitel „Sebalds Steller“ nachgegangen. Dabei wird wahrend der Analyse der Intertextualitat klar, dass sich Sebald in diesem Teil auf den amerikanischen Autoren Corey Ford und seine fiktionale Biographie uber Steller mit dem Titel Where the Sea Breaks Its Back aus dem Jahre 1967 stutzt. Abschließend wird die Frage erhoben, ob es sich dabei weiterhin um eine Referenz zu dem Kalten Krieg handeln konnte. Die in den ersten zwei Teilen von Nach der Natur erarbeitete Vorgehensweise und Analyse der Intertextualitat Sebalds muss im vorletzten Kapitel dieser Arbeit mit der Uberschrift „Sebalds Alter Ego“ adaptiert werden. Es kann gezeigt werden, dass der Erzahler eine Art Alter Ego des Autors darstellt und mit (open full item for complete abstract)

    Committee: Sara Friedrichsmeyer PhD (Committee Chair); Manfred Zimmermann PhD (Committee Co-Chair); Todd Herzog PhD (Committee Member) Subjects: German literature
  • 6. Richards, Kevin Soldiering On: Images of the German Soldier (1985-2008)

    Doctor of Philosophy, The Ohio State University, 2012, Germanic Languages and Literatures

    The criminal legacy of National Socialism cast a shadow of perpetration and collaboration upon the post-war image of the German soldier. These negative associations impeded Helmut Kohl's policy to normalize the state use of the military in the mid-eighties, which prompted a politically driven public relations campaign to revise the image of the German soldier. This influx of new narratives produced a dynamic interplay between political rhetoric and literature that informed and challenged the intuitive representations of the German soldier that anchor positions of German national identity in public culture. This study traces that interplay via the positioning of those representations in relation to prototypes of villains, victims, and heroes in varying rescue narrative accounts in three genre of written culture in Germany since 1985: that is, since the overt attempts to change the function of the Bundeswehr in the context of (West) German normalization began to succeed. These genre are (1) security publications (and their political and academic legitimizations), (2) popular fantasy literature, and (3) texts in the tradition of the Vergangenheitsbewaltigung. I find that the accounts presented in the government's White Papers and by Kohl, Nolte, and Hillgruber in the mid-1980s gathered momentum over the course of three decades and dislodged the dominant association of the German soldier with the villainy of National Socialism. The new dominant account established in the genre of security policy publications and their political and academic legitimations positions the German soldier as a European Christian hero and displaces the villainy previously associated with his image onto foreign powers and their populace. An overview of the developments in the genre of popular Nibelung adaptations echoes the development of the antagonistic accounts in the White Papers of their periods, but then these adaptations conform to the generic expectations of the Nibelungen material, tho (open full item for complete abstract)

    Committee: John Davidson PhD (Advisor); Anna Grotans (Committee Member); Katra Byram (Committee Member) Subjects: Germanic Literature; Modern History
  • 7. Vespa, Jonathan Union Formation in Later Life: The Economic Determinants of Cohabitation and Marriage Among Older Adults

    Doctor of Philosophy, The Ohio State University, 2010, Sociology

    This study examines union formation at older ages. It explores the process of entering marriage and cohabitation among single Americans who are at least 50 years old, and explores whether older cohabiters marry, separate, or remain cohabiting. The goal is to document the prevalence, timing, and patterns of union formation during older adulthood, concentrating especially on the gendered role of economic determinants. To explore these research questions, the study draws on Becker's independence hypothesis and Oppenheimer's theory of marriage timing. It uses 5 waves of longitudinal data from the 1998–2006 rounds of the Health and Retirement Study and employs event history analysis. Findings suggest that, among single older adults, wealth increases the likelihood of marrying and cohabiting as compared to staying single, regardless of gender, while wealth has no effect on the likelihood of cohabiting versus marrying. Only among older women do financial transfers increase the risk of remaining single or of cohabiting rather than marrying. These findings support Oppenheimer's theory of marriage timing in that the resources of both men and women facilitate union formation. The findings are in contrast to what is known about young adults' cohabiting unions, however. Among young adults, cohabiters are economically disadvantaged compared to married individuals but among older adults this does not appear to be the case. Cohabiting unions among older adults also appear relatively stable. Roughly two thirds of older adults' cohabiting unions are intact after 2 years and half after 5 years, although these estimates vary largely by age. The cohabiting unions of women who are at least 65 years old are the most stable and least likely to end in marriage compared to similarly aged male cohabiters and those in their 50s and early 60s. Wealth has a pronounced stabilizing effect on older women's cohabitations, deterring marriage and separation. In contrast, wealth has a transformative (open full item for complete abstract)

    Committee: Zhenchao Qian PhD (Committee Chair); Elizabeth Cooksey PhD (Committee Member); Elizabeth Menaghan PhD (Committee Member) Subjects: Demographics; Sociology
  • 8. Gladstone, Amy Assessing the Genetic Counseling Needs of Parents who have Adopted a Child with Duchenne or Becker Muscular Dystrophy

    MS, University of Cincinnati, 2013, Medicine: Genetic Counseling

    Introduction: Duchenne / Becker muscular dystrophy (DBMD) is an x-linked condition with a wide variation of clinical presentation due to specific gene mutations and the gender of the affected individual. For families of the most severely affected male patients, care needs, natural history, and potential interventions are paramount. In contrast, reproductive risks may be important for less severely affected individuals as in the case of Becker phenotype or DBMD carrier females. The published literature has suggested the caregiver burden and poor prognosis of DBMD has an impact on the biological family as a whole. Additionally, published literature suggests a high disruption rate of adoptions that involve a child with special needs. However, the literature does not currently describe the role of genetic counselors in addressing the needs of families who have adopted a child with DBMD. Purpose: The purpose of this study was to determine the needs of adoptive families with sons diagnosed with DBMD, and how genetic counseling could be tailored to improve this population's experience. Methods: Participants were adoptive parents of males who were under age 18 and had a DBMD Diagnosis. They were recruited through Cincinnati Children's Hospital Medical Center or Duchenne Connect. Semi-structured qualitative interviews were conducted by telephone with use of an interview guide. The interview content was analyzed for recurrent themes using NVivo© software. These themes were organized into categories to summarize the findings. Results: Thirteen adoptive parents were interviewed. Their needs, relative to the diagnosis of DBMD, genetic counseling, and the genetics information, were not specific to adoptive families. In addition to the anticipated themes, 2 adoption specific points were described. Parents of adopted children with DBMD place importance on communicating the diagnostic implication of DBMD to the biological parents. Second, adoptive parents who questioned thei (open full item for complete abstract)

    Committee: Robert Hopkin M.D. (Committee Chair); Martha Walker (Committee Member) Subjects: Surgery