Polychlorinated biphenyls (PCBs) are synthetic persistent organic compounds that are known to be carcinogenic to humans. Changes in telomerase activity and telomere length are hallmarks of aging and carcinogenesis. Retention of telomerase activity and long telomeres are key characteristics of stem cells and progenitor cells. I hypothesize that PCBs modulate telomerase activity and telomeres of hematopoietic stem cells and progenitor cells via interference of gene regulation and potentially disrupt cell differentiation. To investigate this possibility, I used progenitor-like cells, human promyelocytic leukemia cells (HL-60), and stem cells from rat bone marrow. I show that PCB126 and PCB153 display toxic effects on telomerase activity, telomere length and their related gene expression in progenitor-like HL-60 cells, but they did not exert much effect on differentiation. Further, an in vivo/in vitro study using rat bone marrow cells shows that PCB126-induced hematotoxicity, evidenced by reduction in telomerase activity and TERT gene expression, an increase of the differentiation and a change in the differentiation direction towards granulocytes, which indicate an effect on stem cell function. I also show that the most potent dioxin-like congener, PCB126, regulates hTERT gene expression by activation of the AhR pathway. Both AhR and ARNT work together as a repressor of hTERT transcription. This research improves our understanding of mechanisms of PCB126 and PCB153 toxicity on hematopoietic stem cells and progenitor cells, which will ultimately have significant implications for human health.

There is an increasing demand for subscore reporting in the testing industry. Many testing programs already include subscores as part of their score report or consider a plan of reporting subscores. However, relatively few studies have been conducted on subscore equating. The purpose of this dissertation is to address the necessity for subscore equating and to evaluate the performance of various equating methods for subscores. Assuming the random groups design and number-correct scoring, this dissertation analyzed two sets of real data and simulated data with four study factors including test dimensionality, subtest length, form difference in difficulty, and sample size. Equating methods considered in this dissertation were linear equating, equipercentile equating, equipercentile with log-linear presmoothing, equipercentile equating with cubic-spline postsmoothing, IRT true score equating using a three-parameter logistic model (3PL) with separate calibration (3PsepT), IRT observed score equating using 3PL with separate calibration (3PsepO), IRT true score equating using 3PL with simultaneous calibration (3PsimT), IRT observed score equating using 3PL with simultaneous calibration (3PsimO), IRT true score equating using a bifactor model (BF) with simultaneous calibration (BFT), and IRT observed score equating using BF with simultaneous calibration (BFO). They were compared to identity equating and evaluated with respect to systematic, random, and total errors of equating. The main findings of this dissertation were as follows: (1) reporting subscores without equating would provide misleading information in terms of score profiles; (2) reporting subscores without a pre-specified test specification would bring practical issues such as constructing alternate subtest forms with comparable difficulty, conducting equating between forms with different lengths, and deciding an appropriate score scale to be reported; (3) the best performing subscore equating method, overall, was 3PsepO followed by equipercentile equating with presmoothing, and the worst performing method was BFT; (4) simultaneous calibration involving other subtest items in the calibration process yielded larger bias but smaller random error than did separate calibration, indicating that borrowing information from other subtests increased bias but decreased random error in subscore equating; (5) BFO performed the best when a test is multidimensional, form difference is small, subtest length is short, or sample size is small; (6) equating results for BFT and BFO were affected by the magnitude of factor loading and variability for the estimated general and specific factors; and (7) smoothing improved equating results, in general.

Vulvodynia is a chronic pain condition in which women experience extreme discomfort and pain during sexual intercourse. Although widely misdiagnosed and under-diagnosed, many women suffer from vulvodynia, with prevalence rates estimated as high as 16% within the United States (U.S.) However, very little is known as to what causes this chronic pain condition, resulting in inconsistent and varied treatment protocols. In turn, women with vulvodynia often report experiencing multidimensional levels of distress, particularly psychological, sexual, and relational in nature. It is also evident that vulvodynia can negatively impact women’s gender identity, especially the working definition of womanhood. The purpose of this qualitative study was to utilize Interpretative Phenomenological Analysis to develop greater understanding and insight as to the ways in which the lived experience of vulvodynia impacted four heterosexual women’s gender identity. Results of this study revealed the following four superordinate themes and seven subordinate themes: 1) critical time periods (i) initial adjustment to vulvodynia after first sexual intercourse was the most difficult time period, (ii) diagnosis was a turning point, and (iii) acceptance of vulvodynia and development of healthy coping strategies; 2) alienation and isolation (iv) feeling inherently different from other women and (v) feeling misunderstood, dismissed, and not believed by others, especially by medical professionals; 3) positive impacts upon life (vi) finding my voice and (vii) reclaiming and renewed appreciation for my body and my physical self; and 4) personalized definitions of womanhood based on individuals’ lived experiences and social contexts. In conclusion, implications for healthcare providers and future directions of research are offered.

Huntington's disease (HD) is an autosomal dominant neurodegenerative disease caused by a mutation involving an expansion of the CAG trinucleotide repeats in the gene encoding for huntingtin (HTT) protein. The discovery of the disease-causing faulty gene (mutant huntingtin; mHTT) has enabled valid presymptomatic gene assessment for HD with results being categorized as ‘gene-expanded (GE; CAG repeats ≥ 36)' or ‘gene non-expanded (GNE)'. Individuals tested to be gene-expanded are destined to develop HD symptoms and will receive clinical diagnosis at an average age of 40 years when abnormal motor symptoms manifest. Those who are GNE will not develop HD. The availability of genetic testing has also provided a valuable research opportunity to study the pathoetiology of HD in PreHD subjects (those tested to be ‘gene-expanded' but are in the prediagnostic stage of HD). The genetic mutation results in widespread neuronal degeneration preferentially within the striatum. The clinical manifestations of HD include a triad of motor, cognitive and psychiatric symptoms. Challenging the classical view of HD as a neurodegenerative disease, recent studies have brought about a conceptual shift to include abnormal neurodevelopmental aspects in the etiology of HD1, based on the notion that lifelong HTT gene mutation may compromise HTT's crucial role in normal brain development. The fronto-striatal circuitry has been a main interest in HD research for its profound pathological association with symptom manifestation and marked neuroanatomical change. However, no study to date has investigated the neuropathological alteration of the fronto-striatal circuitry during childhood in mHTT carriers. In line with the proposed new perspective, the overall hypothesis of the current proposal is that the deteriorating effect of mHTT on the fronto-striatal circuits stems from abnormal development of these circuits. Therefore, the main goal of the current study was to enhance our understanding of how mHTT alters the evolving capacity of the fronto-striatal circuitry from a developmental perspective. To this end, the study examined the fronto-striatal circuit structure (using magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI)) and function (using resting state functional MRI and cognitive/behavior tests) in children (6-18 years of age) at risk for HD. Healthy control children with no family history of HD were also evaluated. For research purposes only, children at risk for HD were genotyped and designated as GE or GNE based the result of their genetic testing. While the assessment of the fronto-striatal circuit development focused on anatomical delineations, the tests of the fronto-striatal circuit functionality were carried out separately for the three distinct cognitive, motor and affective loops within the fronto-striatal circuitry. The overall aim of the project was to evaluate the effect of mHTT on subcortical brain structures, white matter connection development and functional integrity of the cognitive, motor and affective loops within the fronto-striatal circuitry in Gene-Expanded (GE) children compared to those of Healthy Control (HC) children and again to those who are Gene Non-Expanded (GNE). Test of the hypothesized mHTT-associated developmental alteration of the fronto-striatal circuitry was addressed in two specific aims: Specific Aim #1: To observe subcortical gray matter volumes and white matter integrity of the fronto-striatal circuitry in children at risk for HD Decline in corpus striatal volume as well as aberrant fronto-striatal circuit connectivity has been reported in manifest HD patients and also in preHD adults.2-4 However, there is no experimental evidence of the onset or pattern of the pathophysiological change in the fronto-striatal circuitry. Therefore, volumes of subcortical structures and white matter integrity were measured in order to assess the development of the fronto-striatal circuitry in children at risk for HD. Specific Aim #2: To assess the functionalities of specific fronto-striatal circuit loops in children at risk for HD Functional abnormalities of the fronto-striatal circuitry have been observed in HD patients as well as in preHD adults.5 In order to closely examine the mHTT effect on fronto-striatal circuit function, resting state functional connectivity as well as performances on cognitive and behavioral tasks tapping into the functionality of the three fronto-striatal loops were evaluated in children at risk for HD. It was hypothesized that GE children would have diminished fronto-striatal circuit function. The GE children were predicted to show statistically significant deficits in 1) resting state functional connectivity between specific frontal lobe areas and striatal sub-regions, 2) cognitive control, 3) motoric control and 4) behavior control when compared to healthy controls and children without the HTT CAG expansion. The current study reports the baseline profile of the fronto-striatal structure and function in children at risk for HD. We have found that children who are on average 30 years ahead of HD diagnosis to have developmental alterations in the brain structure and function directly linked to the effect of mHTT. Brain morphology analysis revealed specific subcortical gray and white matter changes. The changes include disproportionately smaller caudate and putamen volumes and increased radial diffusivity localized to the external capsule which were more evident in males with HTT gene expansion. Fronto-striatal circuit functional assessment revealed a drop in motor functionality (both at rest and active performance) and externalizing behavior problems indicative of compromised inhibition than aggression. Children from HD families but do not have the genetic mutation also showed development aberrations in both brain structure and function when compared to healthy controls. Importantly, the altered structural morphology and functional profile seen in the GNE group differed from that of the GE children, emphasizing the impact of mHTT. The findings from those who share similar household environment but differ in genetic expansion status are important in highlighting the potential interaction of gene-environment effect on the manifestation of mHTT related changes seen in the children with the genetic expansion for HD. Investigation of subtle but persistent effects of mHTT on normal neural developmental processes may further our understanding of the pathogenesis of HD. Continuous longitudinal comprehensive assessments of the mHTT associated neurophenotype would aid in prognostic scenario estimation and thereby lead to effective clinical decision making to maximize the benefit of early intervention.

An analysis of experiences of immigrant parents, in a Midwestern college community, accessing services for their child with a disability. A qualitative study using phenomenological theory was used wherein access to services was explored from the parents lived experience. Four immigrant parents were chosen using purposive sampling. Grand tour questions were asked leading to follow-up questions based on respondent answers. Interviews were audio recorded in a location chosen by respondents, and transcribed. Home environment and interactions with child were noted. Grounded theory emerged from analysis using the constant comparative method. Transcripts were read multiple times and categories began to emerge. Based on emergent categories transcripts were cut into segments and categorized accordingly. Comparisons of categories led to reanalysis and emergence of three primary themes; experience of accessing services, feelings about services, and factors affecting experience of accessing services. To enhance credibility, negative case analysis was used to incorporate differential experiences. Thick description was used to increase transferability. Dependability and Confirmability were addressed using an audit process. Two parallel theories emerged from the analysis; one regarding factors leading to positive experiences of accessing services, one regarding factors leading to negative experiences. The theories are supported by original data from the interviews and show how providers, the Department of Human Services, school systems and advocates can improve the situation. This study adds knowledge by exploring a previously unexplored type of community in this research area, but is limited by researcher requirement of English speaking respondents.

As Yet Uncertain: A Portrait in Procession is an installation of prints featuring a combination of image and text. Drawing inspiration from various depictions of the grotesque in art and literature, the project examines the grotesque form, both in body and mind. As Yet Uncertain: A Portrait in Procession observes how the grotesque—a body that is always in the act of becoming—relates to uncertainties and ambivalence in identity and humanity.

Diarrheal disease is one of the leading causes of mortality of children under 5 years of age. Despite this, diarrheal disease is easily preventable through adequate water, sanitation and hygiene. Sanitation access is currently classified as “improved” or “unimproved” based on level of latrine access. This does not account for differences in human behaviors, or differences in exposure risk. A sanitation score was built using behavioral and access data in order to better classify the sanitation environment of a household. Due to low levels of sanitation access and practice of open defecation in Ghana, households in four neighborhoods in Accra, Ghana were selected to participate in the data collection. Data was collected through a survey, environmental sanitary inspections and collection of hand rinse and environmental swab samples. These samples were then tested for fecal indicators, by measuring presence and concentration of E. coli and human Adenovirus. A novel sanitation score based on latrine access and use for each household was created. Hierarchical linear and logistic regression was used to compare the sanitation score to the environmental contamination as indicated by the E. coli and Adenovirus. Higher sanitation scores were significantly associated with increases in Adenovirus concentration (PR=1.6, 95%CI=1.1, 2.2). The sanitation score was not significantly associated with E. coli or presence of Adenovirus. Further development of a sanitation score variable could help to better understand sanitation environments.

No description available.

The People's Republic of China is home to numerous beliefs, practices, and customs dating back hundreds, if not thousands of years. In the time since the death of Mao Zedong, many practices have been revived, including the practice of spirit possession. Through careful examination of books, articles, videos, and other sources, I have come to the conclusion that individuals now capable of being possessed in China are a break from previously documented spirit-mediums, nor do they fit into the category termed `shamans' best defined by Mircea Eliade and I.M. Lewis. These individual are heirs to a long history, but have innovated as well as revived previous practices. They now embody a new category, one I have termed spirit-worker. Spirit-workers incorporate aspects of both traditional spirit-mediumship as well as what has been termed shamanism. Although I did not have a chance to do my own fieldwork, through looking at the various sources, we can come to understand how spirit-workers have begun to emerge in China, and what the future may hold for these individuals.

The following paper is a summary of my personal process as an actor. My process, as any process is in a constant state of flux. I discuss my current approach to a role from the callback portion of an audition to performance.