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Research has demonstrated that prenatal exposure to antiepileptic drugs is associated with an increased risk of physical malformations. The potential risk such exposure conveys to the developing brain and therefore the later cognitive functioning of the child is now the focus of both national and international research. This thesis investigated the relationship between prenatal exposure to antiepileptic drugs and child cognitive functioning. This investigation was undertaken in three phases: a systematic review of the published literature; an original research piece investigating prenatal exposure to sodium valproate and levetiracetam and finally a critical review of the research undertaken as part of this thesis and in the wider published literature. The systematic review identified 30 studies which had investigated the cognitive abilities of children with a history of prenatal exposure to antiepileptic drugs. Methodological quality of the studies was considered against the criteria of the Newcastle Ottawa Scale. Differential findings were noted across the antiepileptic drug types, with the largest number of studies documenting increased risks associated with prenatal exposure to sodium valproate. A lack of high quality research across all antiepileptic drugs, and in particular the more recently licensed antiepileptic drugs is highlighted. In the research paper presented here children aged between five and nine years of age exposed to either levetiracetam (n=37), sodium valproate (n=40) or who were born to women with epilepsy but did not require medication (n=43) were recruited from throughout the UK. Demographic and health information was collected from prospective records and supplemented with maternal interview. Formal standardised neuropsychological assessments were undertaken to inform on the child's current level of intellectual, memory, language, attentional and executive functioning. Following adjustment for variables likely to influence child cognitive ability, prenatal exposure to sodium valproate was found to be associated with poorer intellectual and language functioning in a dose dependent manner. When stratified by dose, 57.9% of children exposed to doses of sodium valproate above 800mg daily scored below the average range for their global intellectual ability. Prenatal exposure to levetiracetam was not found to be associated with poorer cognitive functioning. The critical review highlighted a number of methodological strengths of this research, despite time and resource implications. However, consideration should be given to the retrospective nature of this cohort and the potential for recruitment bias. This thesis concludes that women who require continuation of their treatment during pregnancy to control their seizures should be counselled regarding the risks and the benefits of their treatment to allow them to make informed decisions.

Class of 2012 Abstract / Specific Aims: The purpose of this study is to identify the incidence of symptoms associated after exposure to “bath salts,” a term for synthetic cathinones in Arizona. Methods: This is a retrospective chart review of reported exposures to synthetic cathinones to the Arizona Poison and Drug Information Center and the Banner Good Samaritan Poison and Drug Information Center. Main Results: There were 306 cases of synthetic cathinone exposures reviewed and 76.5% were males (n=234) and 23.5% were females (n=72). They were ingested, inhaled, snorted, or injected. The mean age of exposure to synthetic cathinones was 29 years old. The most common symptoms included agitation (48.7%), hallucinations (27.1%), confusion (17.6%), hypertension (21.9%), tachycardia (50.6%), CK elevation (17.3%) and chest pain (9.5%). Less frequent symptoms exhibited in synthetic cathinone abuse included other CNS effects, gastrointestinal symptoms, muscular dysfunction, visual disturbances, and respiratory issues. Conclusions: The symptoms exhibited after exposure to synthetic cathinones were mainly neurologic and cardiovascular. In most cases, symptoms were effectively resolved within 24 to 48 hours after treatment with intravenous fluids and benzodiazepines. In some reports, patients were also given oxygen, anti-emetics, sedatives and anti-psychotic medications. Medical outcomes included major (1.6%), moderate (42.2%) and minor effects (26.1%) while 92 patients were lost to follow-up.

Class of 2015 Abstract / Objectives: The purpose of this study is to explore potential changes in cytokine and interferon expression during co-infection of rhinovirus and Alternaria. Methods: Alternaria filtrates were used to represent Alternaria spores in real-life. The responses were assessed by production of IL-6, IL-8 and interferon, which were measured by ELISA. mRNA expression was detected by quantitative real-time PCR. For data analysis, a two-sided t-test was performed to compare individual experimental groups. Results: Co-infection of Alternaria and rhinovirus enhanced IL-6 and IL-8 production significantly (p< 0.05). However, Alternaria significantly inhibited production of interferon which would otherwise be induced by rhinovirus. Average interferon-beta (IFN β) production was reduced by about 67%; interferon-lambda (IFN λ) was decrease by about 75%. The differences between treatment and control groups were also statistically significant (p < 0.05). Conclusions: These findings suggested that the Alternaria may cause an imbalanced mucosal antiviral response through inhibiting production of interferon while enhancing production of proinflammatory cytokines. These results indicated that Alternaria may lead to inhibit host innate immunity against virus infection, causing more inflammatory response.

It is known that musicians are exposed to potentially harmful sound levels during the course of regular practice, rehearsal, and performance. As a result, these individuals may have an increased risk of noise-induced hearing loss (NIHL). Previous research has shown that in typical daily practice, musicians can exceed daily recommended exposure limits (O'Brien et al., 2013). This research suggests that classical musicians are at high risk for NIHL according to t he National Institute for Occupational Safety and Health ( US Department of Health and Human Services, 1998) and the Occupational Safety and Health Administration (OSHA) guidelines . In addition, distortion-product otoacoustic emission (DPOAE) amplitude shifts have been found to be a sensitive measure for impact of high noise levels on inner-ear function (Lonsbury-Martin et al., 1990). The very livelihoods of musicians could depend on the development of NIHL awareness and prevention strategies. This study reports the sound-level exposures that University of Arizona music students experience in two hours of solitary practice and whether any correlative change in DPOAE amplitude occurred. Utilizing noise dosimetry, measurements of average sound levels and equivalent exposure for an eight-hour period were taken and compared to NIOSH and OSHA guidelines. Changes in inner-ear function were measured by DPOAE amplitudes taken immediately before and after each practice session. The goal of this research is to present data regarding sound-level exposure and address any significance in the correlative relationship between practice-session exposure levels and any shift in outer hair-cell function as determined by pre- and post-practice DPOAE evaluation.

In individuals living with obesity, adipose tissue aids in reducing (H_loss) and also serves as a heat storage compartment. Moreover, lean body mass, which has a higher H_prod than adipose tissue plays a crucial role in energy production and thermoregulation. The extent of resistance to the cold remains underexplored in this population, and it is important to understand these responses given the global obesity rise and its health implications. This study aimed to quantify how various body anthropometric variations affected thermal responses in individuals living with obesity during acute compensable cold exposure. A liquid-conditioned suit, connected to a temperature-controlled water circulating bath set at 10°C, was used for 90 min to elicit a compensable cold response in these individuals. Validated methods regarding subjective thermal comfort and sensations, skin temperature (T_skin; °C), heat production (H_prod; kJ ⋅min⁻¹), metabolic fuel selection and shivering intensity were recorded to determine the effect of obesity (and muscle and fat mass) on thermogenic and thermal responses. Our study revealed that individuals with obesity, like their lean counterparts, manifest an increased H_prod during cold exposure by 1.7 ± 1.3 kJ ⋅min⁻¹. However, this increase was observed to be lesser in magnitude among individuals living with obesity compared to lean ones. We also explored the source of fuel during cold exposure and found that carbohydrate and lipid oxidation collectively accounted for a significant proportion of H_prod, with lipid oxidation dominating at 61%, and carbohydrates at 21%. Regarding muscle activity, it was observed that a decrease in T_skin incited an increase in shivering. However, similar to the metabolic responses, shivering in this cohort was much less pronounced than in lean individuals. The study opens avenues for further research, addressing the implications of repeated cold exposure and different lengths, temperatures, or modalities on individuals living with obesity.

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The EPA recently completed a major study to evaluate exposure and risk associated with a primary contaminant, radon and its progeny in drinking water (EPA, 1995). This work resulted in the development of a Monte Carlo Simulation model written in the programming language C. The model developed by the EPA has been used to estimate the cancer fatality risk from radon in water for exposed populations served by community ground water supplies, and to provide a quantitative analysis of the uncertainty associated with the calculations (EPA, 1995). This research is a continuation of the study conducted by the EPA. In this project, a Monte Carlo computer model will be developed to evaluate the risk associated with exposure to volatile compounds in drinking water. The model will be based on a computer program (developed previously by the EPA) for estimating the risks associated with exposure to radon in drinking water. The model will be re-implemented in the form of a computer program written in C. The analysis for radon will be extended to include the entire range of contaminants found in drinking water supplies. The initial focus of the project has been on extending the analysis to cover the ingestion exposure pathway for volatile compounds, but ultimately the risk via ingestion and dermal sorption will also be evaluated. The integrated model can estimate the risks associated with various levels of contaminants in drinking water and should prove valuable in establishing Maximum Contaminant Levels (MCLs) for the entire range of contaminants found in water supplies and generated in water treatment and distribution systems. / Master of Science