Because of the potentially harmful repercussions of undiagnosed dysphagia, a quick and accurate assessment is necessary to initiate proper treatment as soon as possible. In many situations and settings, the clinical dysphagia evaluation is the only assessment tool available to the speech-language pathologist for the evaluation of swallowing. Although the clinical evaluation does provide useful information, it is reportedly insensitive for diagnosing some forms of dysphagia. Cervical auscultation and measures of tongue function during swallowing are proposed in this investigation to augment the clinical dysphagia evaluation to improve its accuracy for diagnosing dysphagia. Prior to diagnosing disordered swallowing, however, it is necessary to characterize normal swallowing. One-hundred-and-one healthy participants, ages 20-79, with no history of swallowing impairment participated in this investigation. Participants consumed teaspoon boluses of puree, honey, thin, and soft consistencies while the sounds of swallowing were recorded. Participants also consumed 30 ml boluses of honey and thin consistencies while their peak tongue strengths were measured. Descriptive statistics were calculated and reported for the duration of the acoustic swallowing signal, the duration to the peak intensity of the signal, the peak intensity of the signal, the frequency of the peak intensity of the swallow, and the peak frequency of the swallow, as was the mean peak anterior tongue strength during swallowing. Correlations between the variables were also computed. Analyses were conducted with data collapsed across bolus types, as well as for individual bolus consistencies. The objective of this study was to provide a quantitative characterization of swallowing acoustics and peak anterior tongue strength in a sample of normal individuals. Overall, results compared favorably with previous research. Significant correlations were found between the age and the duration variables (positive), age and the intensity variables (negative), the duration variables (positive), the duration to peak intensity and the frequency at peak intensity (negative), the intensity and the frequency variables (positive), and the frequency variables (positive). The current study can serve as a point of reference for future studies, which should further investigate normal swallowing across multiple bolus consistencies and volumes, and eventually compare these measures to those with individuals with disordered swallowing. / A Dissertation submitted to the Department of Communication Disorders in partial fulfillment of the requirements for the degree of Doctor of Philosophy. / Degree Awarded: Summer Semester, 2003. / Date of Defense: June 12, 2003. / Undiagnosed Dysphagia / Includes bibliographical references. / Richard J. Morris, Professor Directing Dissertation; Gary W. Peterson, Outside Committee Member; Julie A. G. Stierwalt, Committee Member; Leonard L. LaPointe, Committee Member.

Theory of Mind (ToM) involves a person's ability to infer what another person knows, thus taking his or her perspective. Initial evidence has been presented for a ToM impairment in individuals with mild to moderate Alzheimer's disease (AD), however preliminary investigations have failed to dissociate theory of mind difficulty from impairments in general inferencing, executive functions, and working memory. Deficits in any of these areas could be sufficient to explain the apparent ToM impairment in the AD population. Ten participants with mild to moderate AD profiles completed first order and second order false belief tasks with and without memory support, and their performances on ToM testing were compared to the performances of elderly controls. All theory of mind testing was controlled with memory, comprehension, and general inferencing questions, and AD participants completed neuropsychological testing to concurrently assess general cognitive functioning, memory, and executive functioning. Independent and paired t-tests compared experimental and control group ToM performances. Correlations assessed relations between ToM and neurocognitve test performances. Descriptive statistics were calculated, and individual case analyses for performances of AD participants were presented. Results indicated that AD participants did not exhibit a specific ToM difficulty as compared to control participants when support for memory was not provided. However, significant group differences for specific ToM impairment that appeared to be separable from comprehension, memory and general inferencing difficulties emerged during ToM testing when support for memory was provided. On individual case analysis, eight of the ten AD participants exhibited a mild, specific ToM difficulty. Correlations between ToM performance and neurocognitive test performances were not significant; however four of the eight AD participants who exhibited specific, ToM difficulty also had difficulty with executive function testing. The results of the current study indicate that individuals with mild to moderate AD may possess an underlying, mild, specific ToM impairment which becomes apparent during supported memory testing. Such mild ToM impairment in high to moderate AD individuals must be further investigated, and possible contributions of executive function impairments to apparent ToM difficulty further explored before the current results can be confidently generalized to a larger AD population. / A Dissertation submitted to the Department of Communication Disorders in partial fulfillment of the requirements for the degree of Doctor of Philosophy. / Degree Awarded: Summer Semester, 2004. / Date of Defense: June 15, 2004. / Mentalizing, Mental Inferencing Dementia, Alzheimer's Disease, Perspective Taking, Theory of Mind / Includes bibliographical references. / Michelle S. Bourgeois, Professor Directing Dissertation; Michael E. Rashotte, Outside Committee Member; Howard Goldstein, Committee Member; Leonard L. LaPointe, Committee Member.

Introduction: Although there is a general convergence of research which indicates that children with autism spectrum disorders (ASD) have deficits in play behavior, substantial gaps remain in our knowledge of play in children with ASD. Areas in need of more investigation include research focusing on very early development of play skills in children with ASD, study of the type or types of play impaired in children with ASD, examination of how individual variation in play relates to the three diagnostic domains of ASD, and study of the underlying theories that may account for play differences observed in this population. Method: This prospective study examined play behavior in children between 18 and 24 months of age who were later diagnosed with ASD (n=48). These children were matched with groups of children with developmental delay (DD) in whom ASD had been ruled out (n=25) and children with typical development (TD; n=48). Precise measures of proportion and rate of exploratory, combinatorial, and functional and symbolic play actions were obtained through systematic observation of Behavior Samples from the Communication and Symbolic Behavior Scales (Wetherby & Prizant, 2002). Results: Children with ASD demonstrated significantly higher proportions of exploratory play behavior than children in the TD group, but not the DD group. Children in the ASD group also demonstrated significantly lower proportions and rates of functional and symbolic play behavior than children in the TD group. In the ASD group, functional play behaviors were significantly related to concurrent social communication skills and repetitive movements, as well as nonverbal development assessed at the time of the third birthday. In addition, exploratory play in the ASD group was significantly related to concurrent symbolic skills and repetitive movements, as well as social affect scores at age three. Discussion: The results add important information to the play literature in ASD about the type of play deficits found in very early development and their relationship to other diagnostic domains central to ASD. The results have important implications for improving early identification of play deficits in this population. / A Dissertation submitted to the School of Communication Science and Disorders in partial fulfillment of the requirements for the degree of Doctor of Philosophy. / Degree Awarded: Fall Semester, 2009. / Date of Defense: October 27, 2009. / Toddlers, Play, Autism / Includes bibliographical references. / Amy M. Wetherby, Professor Directing Dissertation; Chris Schatschneider, University Representative; Juliann Woods, Committee Member; Joanne Lasker, Committee Member.

Schizoaffective Disorder remains poorly understood. Experts still disagree on whether it is a discrete disorder; whether it exists on a spectrum between Bipolar Disorder and Schizophrenia or whether it even exists. Objectives: The study aimed to describe the demographic, clinical and treatment profile of mental health care users (MHCUs) diagnosed with Schizoaffective Disorder at a regional hospital (Helen Joseph Hospital) in Johannesburg, Gauteng. It also aimed to determine the degree of agreement between the clinicians‟ diagnosis and Operational Criteria (OPCRIT). Methods: All MHCUs at Helen Joseph Hospital psychiatric unit with a discharge diagnosis of Schizoaffective Disorder between January 2004 and December 2010 were included. The demographic, clinical and treatment profiles as well as data required for OPCRIT were extracted from hospital records and discharge summaries. Results: The main findings were that most MHCUs diagnosed with Schizoaffective Disorder were female with a mean age of illness onset of 25 years; had impaired social, occupational and interpersonal functioning; had a family history of mood disorders; were non-adherent on admission and were treated with at least 1 antipsychotic and 1 mood stabiliser. Also, there was no agreement between the clinicians‟ diagnosis and OPCRIT. Conclusion: More rigorous research is needed to accurately describe the profile of MHCUs diagnosed with Schizoaffective Disorder to improve understanding and management of their condition.

Thesis(Ph.D.)--Case Western Reserve University, 2010 / Title from PDF (viewed on 2010-01-28) Department of Psychology Includes abstract Includes bibliographical references and appendices Available online via the OhioLINK ETD Center

With the completion of human genome sequencing project and the rapid development of sequencing technologies, our capacity in tackling with genetic and genomic changes that underlie human diseases has never been greater. The recent successes in identifying disease causal single nucleotide variations (SNVs) for Mendelian disorders using whole exome sequencing may bring us one step further to understand the pathogenesis of Mendelian diseases. However, many hurdles need to be overcome before the promises can become widespread reality. In this study, we investigated various strategies and designed a toolkit named PriSNV for SNV identification and prioritization, respectively. The SNV identification pipeline including read alignment, PCR duplication removal, indel realignment, base quality score recalibration, SNV and genotype calling was examined by simulation and real sequencing data. By incorporating sequencing errors and small indels, most of the read alignment software can achieve satisfied results. Nonetheless, the reads with medium size and large indels are prone to be wrongly mapped to the reference genome due to the limitation of gap opening strategies of available read alignment software. In addition, although mapping quality can only reflect certain information of the mapping error rate, it is still important to be adopted to filter out obvious read alignment errors. The PCR duplication removal, indel realignment and base quality score recalibration have proven to be necessary and can substantially reduce the false positive SNV calls. Based on the same quality criterion, Varscan performs as the most sensitive software for SNV calling, unfortunately at mean time the false positive calls are enriched in its result. In order to prioritize the small subset of functionally important variants from tens of thousands of variants in whole human exome, we developed a toolkit called PriSNV, a systematic prioritization pipeline that makes use of information on variant quality, gene candidacy based on the number of novel nonsynonymous mutations in a gene, gene functional annotation, known involvement in the disease or relevant pathways, and location in linkage regions. Prediction of functional impact of the coding variants is also used to aid the search for causal mutations in Mendelian disorders. For the patient affected by Chron's disease, the candidate genes can be substantially reduced from 9615 to 3 by the gene selection strategies implemented in PriSNV. In general, our results for SNV identification can help the biologists to realize the limitation of available software and shed light on the development of new strategies for accurately identifying SNV calls in the future. PriSNV, the software we developed for SNV prioritization, can provide significant help to biologists in prioritizing SNV calls in a systematic way and reducing search space for further analysis and experimental verification. / published_or_final_version / Paediatrics and Adolescent Medicine / Master / Master of Philosophy

Recent founder mutations may play important roles in complex diseases and Mendelian disorders. Detecting shared haplotypes of identity by descent (IBD) could facilitate discovery of these mutations. Several programs address this such as threshold-based methods on genetic distance and probabilistic model-based methods, but they are usually limited to only detecting pair-wise shared haplotypes and not providing a comparison between cases and controls. In this study, a novel algorithm and a applied software package (HaploShare)is developed to detect extended haplotypes that are shared by multiple individuals, which also allows comparisons between cases and controls. A catalog of haplotypes is firstly generated from healthy controls from the same population and used for phasing genotypes in cases. By accounting for all possible haplotype pairs that could explain the genotypes for each individual in a given haplotype block and possible transitions between blocks, the effect of phase uncertainty on detection power is minimized. In cases, haplotypes shared by pairs are identified and used to detect sharing of these haplotypes by different pairs. A likelihood ratio of a shared haplotype due to IBD or chance is estimated for each extended haplotype. Controls are used similarly through many rounds of simulations to obtain an empirical null distribution of the largest likelihood ratios of shared haplotypes, to give statistical estimates of shared haplotypes detected in cases that may be associated with an underlying disease. Series of tests were performed to investigate the performance of HaploShare. Simulations of shared haplotypes demonstrated that HaploShare has better power not only on the detection of pair-wise shared haplotypes but multiple shared haplotypes in most of the simulation scenarios, comparing with other four commonly used programs. False positive rate (FPR) and the false discovery rate (FDR) were also evaluated by statistical calculation. According to the result, both of the two values were extremely low (FPR = 6.28x10-6 , FDR = 0.006), indicating that very few randomly shared haplotypes can be wrongly reported as IBD by HaploShare. HaploShare was also tested on real cases on population data and family linkage analysis. 14 out of 173 Hirschsprung's disease cases were reported by HaploShare of carrying a common haplotype of 250 kb in length, which was consistent with previous findings by direct genotyping and candidate approach. Another testing case is an affected family with 8 cases and 9 unaffected individuals. Disease linked region can be correctly identified by traditional methods if all the data and the entire pedigree were provided. HaploShare showed the ability to locate the shared region even when very limited cases are available, which is clearly beyond the detection power of traditional methods. The results from empirical simulations and real case applications indicate that HaploShare could effectively make use of population genotype information to improve the power of detection of shared haplotypes. The method may extend the findings in human genetics of both complex and single gene diseases. / published_or_final_version / Psychiatry / Doctoral / Doctor of Philosophy

No description available.

Thesis (Psy.D.)--University of Hong Kong, 2008. / Includes bibliographical references (p. 119-133).

Thesis (Ph. D.)--University of Washington, 1997. / Vita. Includes bibliographical references (leaves [108]-119).