Doctor of Philosophy, Case Western Reserve University, 2013, Genetics

Testicular germ cell tumours (TGCTs), which comprise 95% of all testicular cancers, are a group of neoplasms that affect young men. In the last 40 years, the incidence of this cancer has steadily risen throughout the world. Despite the strong heritability of the disease, few genetic or epigenetic risk factors have been identified. Metastases are a prominent feature of the human disease and are responsible for most of the morbidity and mortality associated with TGCTs. The 129 strain family of mice develop spontaneous TGCTs and are a useful organism to study this disease, but the applicability to human disease is subject to debate. We discovered that the mouse model also develops spontaneous metastases in approximately 11% of affected males, suggesting that TGCTs in mice may be more relevant to human TGCTs than previously thought. Moreover, metastasis rates remain consistent between 129 strains with TGCT modifier genes, even when TGCT rates vary. This suggests that the TGCT genetic susceptibility found in 129 strain mice may include a predisposition to metastasis. In order to further characterize one of these genetic modifiers, Dnd1Ter, we created Dnd1 knockout mice and have found several new functions for DND1. Surprisingly, we found that complete loss of DND1 is embryonically lethal, and that intercrossing animals with Dnd1KO alleles reveals a Dnd1 segregation bias. We have also shown that the most powerful TGCT modifier gene in mice, Dnd1Ter, is not a loss of function allele. Loss of a copy of Dnd1 does not affect TGCT rates, but the presence of the Dnd1Ter allele significantly increases TGCT rates. This increase is dose-dependent; a second copy of Dnd1Ter further increases TGCT rates. We have also found that the pro-oncogenic effects of Dnd1Ter are not limited to testicular cancer; it also increases polyp numbers and burden in an APCMIN mouse model of intestinal polyposis. These results show that the mouse model of TGCTs may allow for experimental inv (open full item for complete abstract)

Committee: Joseph Nadeau (Advisor); Helen Salz (Advisor); Hua Lou (Committee Chair); Ronald Conlon (Committee Member); Zhenghe (John) Wang (Committee Member); Ruth Keri (Committee Member) Subjects: Biomedical Research; Developmental Biology; Genetics

MA, Kent State University, 2024, College of Arts and Sciences / Department of Psychological Sciences

Obesity is associated with adverse neurocognitive outcomes, including greater risk for cognitive impairment. Bariatric surgery (BS) patients show improved cognitive functioning postoperatively, though evidence suggests that weight loss is not the primary mechanism for this improvement. Physical activity (PA) and sedentary behavior (SB) may play an important role in the cognitive outcomes of BS patients, given that greater PA and less SB is associated with better cognitive functioning in other populations. The current study prospectively examined the relationship among light-intensity PA (LPA) and SB with cognitive functioning in BS patients, as well as possible sex differences in these relationships. A total of 138 participants (42.9 ± 10.5 years of age, BMI of 46.3 ± 7.3 kg/m²) undergoing Roux-en-Y Gastric Bypass or Sleeve Gastrectomy were included in the study and attended study visits at preoperative baseline, as well as at one-month, six-month, and twelve-months postoperative follow-up. Participants completed the NIH Toolbox for the Assessment of Neurological and Behavioral Function, a computerized neuropsychological battery that assesses functioning across several domains at all time points. Participants wore a waist-mounted accelerometer for seven consecutive days prior to each study visit to measure average daily minutes spent in SB, LPA, and moderate-to-vigorous intensity PA. Body mass index (BMI) and percentage of excess body weight loss (%EBWL) were calculated using height and weight at each visit. Multilevel modeling was used to examine the associations among SB and LPA with cognitive function over the course of the study, controlling for %EBWL, as well as the possible moderating role of sex in these associations. We hypothesized that greater LPA and lower SB would be associated with greater cognitive functioning, and that these associations would be stronger for women. Results showed that SB displayed a negative relationship with Lis (open full item for complete abstract)

Committee: John Gunstad (Advisor); John Updegraff (Committee Member); Mary Beth Spitznagel (Committee Member); Jeffrey Ciesla (Advisor) Subjects: Psychology

Doctor of Philosophy, The Ohio State University, 2021, Speech and Hearing Science

Children who are deaf or hard-of-hearing (DHH) exhibit considerable variability in their spoken language and executive function (EF) outcomes, despite on-going improvements in sensory aid technology and public health policies that target early diagnosis and intervention. Maternal parenting cognitions and behaviors (e.g., the patterns of interactions and metacognitive processes involved in parenting) are robust predictors of at-risk outcomes in children who are DHH. However, only recently have pediatric researchers recognized that the dyadic relations between mothers and their children occur within the context, organization, and structure of a complex system: the family. Moreover, no models within the hearing sciences have consistently incorporated fathers within a family-systems perspective of child development, representing a critical barrier to understanding pediatric DHH outcomes variability. The Social-Behavioral-Risk model (SBR) of pediatric hearing loss recognizes that child development occurs within ecological and transactional contexts, and that at-risk outcomes are influenced by proximal relations within the family system. However, very little is known about the specific impacts that fathers have on developmental trajectories of children who are DHH. Even less in known about joint coparenting dimensions in families with children who are DHH and their associations with at-risk outcomes. This dissertation consists of four chapters, three of which represent individual manuscripts which examine different relations between paternal characteristics and at-risk DHH developmental domains in families with children with DHH or typical hearing (TH). Chapter 1 provides an introduction to this line of research and lays the foundation for the following three chapters. Chapter 2 examines attachment- and activation-based behaviors of fathers during play and presents evidence that both types of behaviors are associated with EF skills for both groups of children. In particul (open full item for complete abstract)

Committee: Rachael Frush Holt (Advisor); Laura Wagner (Committee Member); Allison Bean (Committee Member); Eric Healy (Committee Member) Subjects: Audiology; Families and Family Life

Master of Science, The Ohio State University, 2020, Public Health

Outcome weighted learning is a weighted classification-based approach for finding the optimal individualized treatment regime to prolong survival when subject characteristics impact response to different treatment options. Previous research on this method utilizes the hinge loss from machine learning to perform classification. However, there are other loss functions for binary classification that could be leveraged, such as the logit loss from logistic regression. This study compares the performance of outcome weighted learning models via simulations with different surrogate loss functions to determine whether the logit loss is a reasonable alternative to the hinge loss. Data are right censored with two possible treatments and decision functions are assumed to be linear. Simulations are conducted under three forms of the true decision function, using a correctly specified model with two covariates and an incorrectly specified model with an extra nuisance covariate. Logit loss and hinge loss outcome weighted learning models are applied to data from a randomized trial on aortic stenosis. Results indicate that the logit loss offers comparable performance to the hinge loss and therefore can be used as an alternative to the latter, though the performance of both outcome weighted learning models may suffer from instability when they are misspecified.

Committee: Andy Ni PhD (Advisor); Bo Lu PhD (Committee Member) Subjects: Biostatistics

Doctor of Philosophy, The Ohio State University, 2018, Speech and Hearing Science

High-frequency sensorineural hearing loss is a common side effect of platinum-based chemotherapies due to the degeneration of cochlear structures. The speech perception of individuals with hearing loss due to chemotherapy has not been as extensively investigated. Studies investigating the speech perception abilities in individuals with hearing loss due to chemotherapy reveal speech perception difficulties and self-perceived hearing handicap greater than expected given pure tone thresholds. This suggests that platinum-based chemotherapies reduce speech perception abilities more than expected given pure-tone thresholds and supports the need for further evaluation of potential underlying mechanisms, such as substantial cochlear damage. The purpose of the present study was to investigate both speech perception abilities and cochlear function in children and adults with hearing loss due to chemotherapy. Speech perception was evaluated for sentence stimuli that were low-pass filtered to create five filter conditions and presented in the presence of speech spectrum noise at three signal-to-noise ratios (SNR). Speech stimuli were presented via digital hearing aids programmed based on the participant's pure tone thresholds. Cochlear function was investigated as a mechanism to identify regions of substantial cochlear damage using Fast Psychophysical Tuning Curves (PTCs) and the Threshold Equalizing Noise (TEN) test. Speech perception and cochlear function were measured in four groups: 30 children and 15 adults with normal hearing, and five children and five adults with hearing loss due to chemotherapy. Participants with hearing impairment generally had poorer speech perception in noise across all filter cut-off and SNR conditions and showed smaller gains in speech perception as the filter-cut off frequency increased when compared to normal-hearing controls. For one child and one adult with hearing impairment, TEN test results demonstrated abnormally high mas (open full item for complete abstract)

Committee: Lawrence Feth Ph.D. (Advisor); Christina Roup Ph.D. (Committee Member); Eric Bielefeld Ph.D. (Committee Member) Subjects: Audiology; Medicine

Master of Arts, The Ohio State University, 2017, Psychology

Obesity is a major public health concern with over a third of Americans considered obese, as defined by a BMI equal to or greater than 30. Obesity is associated with risky decision making which may lead to less engagement in activities that promote weight loss, including diet and physical activity. Engagement in physical activity is associated with less risky decision making and improved executive control. However, the current literature provides limited comparisons of non-obese adults and obese, weight-loss seeking adults on tasks of decision making. The literature also includes limited evaluation of how physical fitness relates to hot decision making, or decision making under ambiguity, and cold decision making, or decision making under risk. The aim of this observational study was to evaluate differences in decision making among non-obese and obese individuals, and to evaluate the relationship of obesity, physical fitness, and decision making. Obese participants (n=50) were recruited and assessed during orientation to a university-based behavioral weight management program, and non-obese participants (n=40) were recruited from the community. All participants completed a demographics questionnaire and four computerized tasks of decision making. Study personnel calculated BMI via height and weight measurements for all participants. Data concerning body fat percentage and meters walked on a 12-minute walk test were collected from obese participants' patient files. The sample was primarily female (84.4%), and Caucasian (84.4%) with an average age of 42.9 (¿11.9) years and an average BMI of 36.3(¿13.9). Pearson correlations, analyses of variance, chi-square analyses, and the PROCESS macro in Statistical Analysis Software (SAS) version 9.2 were used to analyze data. Results provide preliminary evidence for physical fitness as a mediator in the relationship between obesity and decision making such that higher BMI is associated with a riskier decision making, as measure (open full item for complete abstract)

Committee: Charles Emery (Advisor); Melissa Buelow (Committee Member); Julian Thayer (Committee Member) Subjects: Psychology

Master of Science, The Ohio State University, 2015, Materials Science and Engineering

Electron energy-loss spectroscopy (EELS) is capable of probing the electronic structure of materials at the nanometer scale; however, accurate models for the interpretation of energy-loss spectra is lacking, particularly for complex material systems. The focus of this work is on the modeling and interpretation of EELS for two complex systems, bone mineral and the battery cathode material lithium iron phosphate (LFP). For the first case study, DFT was employed to model the spectra of HA and carbonated HA (CHA) using a density of states interpretation. It was found that the twin peak appearance in both HA and CHA may be due to a distribution in the magnitude of core-hole screening on either crystallographically inequivalent sites, meaning the magnitude of screening is site-specific, or across equivalent sites following a general statistical distribution. It was also found that the low-energy shoulder peak that is present in the oxygen K-edge spectra of CHA, as well as the overall broadening seen in the twin peak appearance relative to HA is due to additional states added by the substitutional carbonate groups. The second case study deals with the battery cathode material, lithium iron phosphate (LFP). While considerable work has gone into the predictive modeling capabilities of DFT fore core-loss spectra, the same is not true for the valence loss region, which contains collective excitations effects as well as single-excitation effects. Even less research has focused on the modeling of VEEL spectra for complex highly correlated systems, such as LFP and FP. DFT+U formalism was used to model the complex dielectric function of LFP and delithiated LFP (FP) from which the valence electron energy-loss function could be extracted. The Hubbard correction term, Ueff, was calculated from linear response theory (LRT) found in literature and employed and the corresponding models were compared with models found in literature employing other values. The only major di (open full item for complete abstract)

Committee: David McComb Dr. (Advisor); Wolfgang Windl Dr. (Committee Member) Subjects: Biochemistry; Biomedical Research; Chemistry; Materials Science; Physical Chemistry; Physics

Master of Arts, The Ohio State University, 2013, Geography

Recently, flood damage raises a great concern due to the increasing weather extremes and fast urbanization speed. However, due to limited damage data and crude methodology in this field, few flood damage studies could provide accurate results for flood management. To evaluate current methods of flood damage assessment and provide effective information for flood planning, this study investigate and evaluate the damage assessment method e.g. loss functions which are widely used in damage studies, and study the social vulnerability of local residents as auxiliary information to explain the total flood damage of Hurricane Sandy in New York City. Firstly, two types of loss functions are applied to the flood damage on buildings and subways. The estimates thus obtained is then, compared with the real flood loss report from FEMA. Secondly, as the current benchmark and terminology of flood are based on 1/100 year flood event, current flood protection strategies based on such 1/100 year criteria is facing increasing challenges due to the raising intensity or frequency of floods today. Therefore, a comparison between Sandy’s floodplain and FEMA-produced 1/100 year floodplain is made to improve the awareness and understanding of Sandy’s impact as well as current flood planning. With the consideration of the crude methodologies and limited data of damage study, the third task is to generate a social vulnerability (SoVI) map to account for social and economic damages which are hard to be estimated through current loss functions. The study is ended with several conclusions: 1), those loss functions which only use inundation depth cannot accurately estimate the flood damage in each county. Wind speed could be another indispensable indicator expressing the flood hazard. The damage estimate of subways should include the damage of subway station. In addition, improving the estimates of loss functions for different kinds of objects or property need further adjustments wit (open full item for complete abstract)

Committee: Desheng Liu (Advisor); Ola Ahlqvist (Advisor) Subjects: Geography

PhD, University of Cincinnati, 2010, Engineering : Mechanical Engineering

Simulation-based study of human auditory response characteristics and development of a prototype for advanced noise guideline are two major focuses of this dissertation research. This research was conducted as a part of the long-term effort to develop an improved noise guideline for better protection of the workers exposed to various noise environments. The human auditory responses were studied with simulation models. A human full-ear model derived from an existing model, Auditory Hazard Assessment Algorithm for Human (AHAAH), was utilized as a baseline for the study. Frequency- and time-domain responses of well-known human middle ear network models were cross-compared to estimate expected accuracy of the models and understand their proper use. Responses of the stapes to impulsive noises were investigated by using the middle ear models to understand the effects of the temporal characteristics of impulsive noises on the responses. Available measured transfer functions between the free-field pressure and the stapes response for human and chinchilla were also used to study the auditory response characteristics. The measured transfer functions were refined and reconditioned to make them have equivalent formats. Using the reconstructed transfer functions, time-domain stapes responses of human and chinchilla to impulsive and complex type noises were calculated and compared. Applicability of the noise metrics defined in terms of the stapes response to assess the risk of the noise induced hearing loss was studied. A prototype of an improved noise guideline was developed from existing chinchilla noise exposure data. Applying a new signal processing technique to the time histories of the exposed noises and studying the relationship between the noise metric and the permanent threshold shift (PTS), the dose-response relationship (DRR) was established in a compatible way with the definition used in current human noise guidelines. From the DDR, noise induced hearing loss (NIHL (open full item for complete abstract)

Committee: J. Kim PhD (Committee Chair); William Murphy PhD (Committee Member); Mark Schulz PhD (Committee Member); Teik Lim PhD (Committee Member) Subjects: Mechanical Engineering