Effects of GeneXpert MTB/RIF Testing and GxAlert eHealth Platforms on MDR-TB Diagnosis and Linkage to Care in Sofala Province, Mozambique

Thesis (Master's)--University of Washington, 2016-06

Evaluation of a Post Discharge Intervention on 30-Day Re-admission and Emergency Room Use in Patients with Diabetes A Pilot Program

Thesis (Master's)--University of Washington, 2016-06

Perceptions of Malingering or Factitious Disorder by Army Behavioral health Providers

Thesis (Master's)--University of Washington, 2016-06

Methylomic and Transcriptomic Insights Linking Air Pollution and Atherosclerosis

Thesis (Ph.D.)--University of Washington, 2016-06

Genetic effects of chronic habitat fragmentation on tree species: the case of Sorbus aucuparia in a deforested Scottish landscape

Sustainable forest restoration and management practices require a thorough understanding of the influence that habitat fragmentation has on the processes shaping genetic variation and its distribution in tree populations. We quantified genetic variation at isozyme markers and chloroplast DNA (cpDNA), analysed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in severely fragmented populations of Sorbus aucuparia (Rosaceae) in a single catchment (Moffat) in southern Scotland. Remnants maintain surprisingly high levels of gene diversity (H-E) for isozymes (H-E = 0.195) and cpDNA markers (H-E = 0.490). Estimates are very similar to those from non-fragmented populations in continental Europe, even though the latter were sampled over a much larger spatial scale. Overall, no genetic bottleneck or departures from random mating were detected in the Moffat fragments. However, genetic differentiation among remnants was detected for both types of marker (isozymes Theta(n) = 0.043, cpDNA Theta(c) = 0.131; G-test, P-value < 0.001). In this self-incompatible, insect-pollinated, bird-dispersed tree species, the estimated ratio of pollen flow to seed flow between fragments is close to 1 (r = 1.36). Reduced pollen-mediated gene flow is a likely consequence of habitat fragmentation, but effective seed dispersal by birds is probably helping to maintain high levels of genetic diversity within remnants and reduce genetic differentiation between them.

An Incremental EM-based Learning Approach for On-Line Prediction of Hospital Resource Utilization

Objective: Inpatient length of stay (LOS) is an important measure of hospital activity, health care resource consumption, and patient acuity. This research work aims at developing an incremental expectation maximization (EM) based learning approach on mixture of experts (ME) system for on-line prediction of LOS. The use of a batchmode learning process in most existing artificial neural networks to predict LOS is unrealistic, as the data become available over time and their pattern change dynamically. In contrast, an on-line process is capable of providing an output whenever a new datum becomes available. This on-the-spot information is therefore more useful and practical for making decisions, especially when one deals with a tremendous amount of data. Methods and material: The proposed approach is illustrated using a real example of gastroenteritis LOS data. The data set was extracted from a retrospective cohort study on all infants born in 1995-1997 and their subsequent admissions for gastroenteritis. The total number of admissions in this data set was n = 692. Linked hospitalization records of the cohort were retrieved retrospectively to derive the outcome measure, patient demographics, and associated co-morbidities information. A comparative study of the incremental learning and the batch-mode learning algorithms is considered. The performances of the learning algorithms are compared based on the mean absolute difference (MAD) between the predictions and the actual LOS, and the proportion of predictions with MAD < 1 day (Prop(MAD < 1)). The significance of the comparison is assessed through a regression analysis. Results: The incremental learning algorithm provides better on-line prediction of LOS when the system has gained sufficient training from more examples (MAD = 1.77 days and Prop(MAD < 1) = 54.3%), compared to that using the batch-mode learning. The regression analysis indicates a significant decrease of MAD (p-value = 0.063) and a significant (p-value = 0.044) increase of Prop(MAD

Brachial blood pressure but not carotid arterial waveforms predict cardiovascular events in elderly female hypertensives

Central arterial waveforms and related indices of large artery properties can be determined with relative ease. This would make them an attractive adjunct in the risk stratification for cardiovascular disease. Although they have been associated with some classical risk factors and the presence of coronary disease, their prospective value in predicting cardiovascular outcomes is unknown. The present study determined the relative predictive value for cardiovascular disease-free survival of large artery properties as compared with noninvasive brachial blood pressure alone in a population of elderly female hypertensive subjects. We measured systemic arterial compliance, central systolic pressure, and carotid augmentation index in a subset of female participants in the Second Australian National Blood Pressure Study ( untreated blood pressure 169/88 +/- 12/ 8 mm Hg). There were a total of 53 defined events during a median of 4.1 years of follow-up in 484 women with complete measurements. Although baseline blood pressures at the brachial artery predicted cardiovascular disease-free survival ( hazard ratio [HR], 2.3; 95% CI, 1.3 to 4.1 for pulse pressure >= 81 versus < 81 mm Hg; P = 0.01), no such relation was found for carotid augmentation index ( HR, 0.80; 95% CI, 0.44 to 1.44; P value not significant) or systemic arterial compliance ( HR, 1.25; 95% CI, 0.72 to 2.16; P value not significant). Blood pressure, but not noninvasively measured central arterial waveforms, predict outcome in the older female hypertensive patient. Thus, blood pressure measurement alone is superior to measurement of arterial waveforms in predicting outcome in this group.

O Conflito de Agência Exposto ao Efeito de Mercado: Um Estudo Empírico de Precificação de Ações da Bombril S/A

Esta dissertação apresenta um estudo exploratório que tem como objetivo a avaliação da reação do mercado frente aos problemas de agência e assimetria informacional entre os acionistas majoritários-controladores e os acionistas minoritários de uma empresa brasileira de capital aberto, no tocante ao valor das suas ações negociadas na Bolsa de Valores de São Paulo. O estudo se propõe a investigar o impacto de precificação dessas ações promovendo a análise do seu comportamento frente à divulgação de notícias de crise e fraude da empresa por meio da mídia especializada. A metodologia adotada consiste na aplicação de estudo de eventos para identificação de retornos anormais da empresa desde a divulgação da primeira notícia selecionada, datada de maio de 2001, até a última notícia em outubro de 2005, utilizando-se de procedimentos estatísticos como a regressão linear e aplicação do teste t de student para estimar e comparar os resultados. Os dados foram obtidos por meio do banco de dados da Economática Ltda, conforme acesso realizado na Universidade de São Paulo. Para objeto de pesquisa foi selecionada a empresa Bombril S/A, por estar em evidências quanto a problemas de agência no âmbito do mercado nacional. Os resultados obtidos apontaram que o mercado reagiu significantemente aos anúncios dos conflitos selecionados, apresentando um valor de p-value <0,05 para os blocos de eventos, o que significa a rejeição da hipótese nula, constatando que a evidencia estatística dos dados testados comprova retornos anormais acumulados diferentes de zero. Entretanto, sugere-se novas pesquisas com outros parâmetros de eventos na busca de mais evidências sobre o efeito das informações no preço das ações.

The case for aluminium as the neurotoxin in sporadic Alzheimer's disease

The flash-pattern evoked potential difference (F - P) in man increases with age (93 subjects), correlates with decreasing cognitive ability and when it exceeds a unique critical level the subject is clinically diagnosed as having Alzheimer's disease. Aluminium accumulates in the human brain with age, increases the F - P value close to the critical value in a dose dependent manner, and at such a rate that normal environmental exposure to aluminium accounts for all or nearly all the F - P increases in man. Aluminium neurotoxicity is therefore a major cause of sporadic Alzheimer's disease.

Factors preventing myopia progression with orthokeratology correction

PURPOSE: To examine which baseline measurements constitute predictive factors for axial length growth over 2 years in children wearing orthokeratology contact lenses (OK) and single-vision spectacles (SV). METHODS: Sixty-one children were prospectively assigned to wear either OK (n = 31) or SV (n = 30) for 2 years. The primary outcome measure (dependent variable) was axial length change at 2 years relative to baseline. Other measurements (independent variables) were age, age of myopia onset, gender, myopia progression 2 years before baseline and baseline myopia, anterior chamber depth, corneal power and shape (p value), and iris and pupil diameters as well as parental refraction. The contribution of all independent variables to the 2-year change in axial length was assessed using univariate and multivariate regression analyses. RESULTS: After univariate analyses, smaller increases in axial length were found in the OK group compared to the SV group in children who were older, had earlier onset of myopia, were female, had lower rate of myopia progression before baseline, had less myopia at baseline, had longer anterior chamber depth, had greater corneal power, had more prolate corneal shape, had larger iris diameter, had larger pupil sizes, and had lower levels of parental myopia (all p < 0.05). In multivariate analyses, older age and greater corneal power were associated with smaller increases in axial length in the OK group (both p < 0.05), whereas in SV wearers, smaller iris diameter was associated with smaller increases in axial length (p = 0.021). CONCLUSIONS: Orthokeratology is a successful treatment option in controlling axial elongation compared to SV in children of older age, had earlier onset of myopia, were female, had lower rate of myopia progression before baseline, had lower myopia at baseline, had longer anterior chamber depth, had greater corneal power, had more prolate corneal shape, had larger iris and pupil diameters, and had lower levels of parental myopia. © American Academy of Optometry.

Regional variability in visual field sensitivity during hypercapnia

PURPOSE: Previous investigations have demonstrated a relative vascular autoregulatory inefficiency of the inferior compared to the superior retina in healthy subjects breathing increased CO2. The purpose of this study was to determine whether the superior and inferior visual field sensitivities of healthy eyes are similarly affected during mild hypercapnia. DESIGN: Experimental study. METHODS: Visual field analysis (Humphrey Field Analyser; SITA standard 24-2 program) was carried out on one randomly selected eye of 22 subjects (mean age, 27.7 ± 5 years) during normal room air breathing and isoxic hypercapnia. The Student paired t-tests were used to compare the visual field indices mean deviation (MD) and pattern standard deviation (PSD) for each breathing condition. A secondary, sectoral analysis of mean pointwise sensitivity was performed for each condition. In each case a P value of <.01 was considered statistically significant (Bonferroni corrected). RESULTS: Visual field MD was -0.23 ± 0.95dB during room air breathing and -0.49 ± 1.04dB during hypercapnia (P = .034). Sectoral pointwise mean sensitivity deteriorated by 0.46dB (P = .006) in the upper visual hemifield during hypercapnia, whereas no significant difference was observed for the lower hemifield (P = .331). CONCLUSIONS: The upper visual hemifield exhibited a significantly greater degree of deterioration in pointwise visual field mean sensitivity compared to the lower hemifield during hypercapnic conditions. This suggests that the upper visual hemifield and hence inferior retina is more susceptible to insult during hypercapnia than the superior retina in healthy individuals. A regional susceptibility of inferior retinal function to altered vascular or metabolic effects may account for the earlier and more frequent inferior nerve fibre damage associated with glaucomatous optic neuropathy. © 2003 by Elsevier Science Inc. All rights reserved.

Monocyte subset counts associations with left ventricular systolic function post ST elevation myocardial infarction

Background: Monocytes are implicated in the initiation and progression of theatherosclerotic plaque contributing to plaque instability and rupture. Little is knownof the role played by the 3 phenotypically and functionally different monocytesubpopulations in determining ventricular remodeling following ST elevation my-ocardial infarction (STEMI). Mon1 are "classical" inflammatory monocytes, whilstMon3 are considered reparative with fibroblast deposition ability. The function ofthe newly described Mon2 is yet to be elucidated. Method: STEMI patients (n=196, mean age 62±13 years; 72% male) treatedwith percutaneous revascularization were recruited within the first 24 hours. Pe-ripheral blood monocyte subpopulations were enumerated and characterizedusing flow cytometry after staining for CD14, CD16 and CCR2. Phenotypi-cally, monocyte subpopulations are defined as: CD14+CD16-CCR2+ (Mon1),CD14+CD16+CCR+ (Mon2) and CD14lowCD16+CCR2- (Mon3) cells. Transtho-racic 2D echocardiography was performed within 7 days and 6 months post infarctto assess ventricular volumes, mass, systolic, and diastolic functions. Results: Using linear regression analysis higher counts for Mon1, and lowercounts for Mon2 and Mon3 were significantly associated with the baseline leftventricular ejection fraction (LVEF) within seven days post infarction. At 6 monthspost STEMI lower counts of Mon2 remained positively associated with decreasedLVEF (p value= 0.002).Monocyte subsets correlation with LVEFMonocytes mean florescence Baseline left ventricular Left ventricular ejectionintensity (cells/μl) ejection fraction (%) fraction (%) at 6 months post infarctβ-value P-valueβ-value P-valueTotal Mon0.31 P<0.001 0.360.009Mon 10.019 0.020.070.62Mon 2−0.28 0.001 −0.420.002Mon 3−0.27 0.001 −0.180.21 Conclusion: Peripheral monocytes of all three subsets correlate with LVEF af-ter a myocardial infarction. High counts of the inflammatory Mon1 are associatedwith reduction in the baseline LVEF. Post remodelling, the convalescent EF wasindependently predicted by monocyte subpopulation 2. As lower counts depictednegative ventricular remodeling, this suggests a reparative role for the newly de-scribed Mon2, possibly via myofibroblast deposition and angiogenesis, in contrastto an anticipated inflammatory role.

Analysis and comparison of the moral development of students required to graduate with an ethics course

Accounting students become practitioners facing ethical decision-making challenges that can be subject to various interpretations; hence, the profession is concerned with the appropriateness of their decisions. Moral development of these students has implications for a profession under legal challenges, negative publicity, and government scrutiny. Accounting students' moral development has been studied by examining their responses to moral questions in Rest's Defining Issues Test (DIT), their professional attitudes on Hall's Professionalism Scale Dimensions, and their ethical orientation-based professional commitment and ethical sensitivity. This study extended research in accounting ethics and moral development by examining students in a college where an ethics course is a requirement for graduation. ^ Knowledge of differences in the moral development of accounting students may alert practitioners and educators to potential problems resulting from a lack of ethical understanding as measured by moral development levels. If student moral development levels differ by major, and accounting majors have lower levels than other students, the conclusion may be that this difference is a causative factor for the alleged acts of malfeasance in the profession that may result in malpractice suits. ^ The current study compared 205 accounting, business, and nonbusiness students from a private university. In addition to academic major and completion of an ethics course, the other independent variable was academic level. Gender and age were tested as control variables and Rest's DIT score was the dependent variable. The primary analysis was a 2 x 3 x 3 ANOVA with post hoc tests for results with significant p-value of less than 0.05. ^ The results of this study reveal that students who take an ethics course appear to have a higher level of moral development (p = 0.013), as measured by the (DIT), than students at the same academic level who have not taken an ethics course. In addition, a statistically significant difference (p = 0.034) exists between freshmen who took an ethics class and juniors who did not take an ethics class. For every analysis except one, the lower class year with an ethics class had a higher level of moral development than the higher class year without an ethics class. These results appear to show that ethics education in particular has a greater effect on the level of moral development than education in general. Findings based on the gender specific analyses appear to show that males and females respond differently to the effects of taking an ethics class. The male students do not appear to increase their moral development level after taking an ethics course (p = 0.693) but male levels of moral development differ significantly (p = 0.003) by major. Female levels of moral development appear to increase after taking an ethics course (p = 0.002). However, they do not differ according to major (p = 0.097). ^ These findings indicate that accounting students should be required to have a class in ethics as part of their college curriculum. Students with an ethics class have a significantly higher level of moral development. The challenges facing the profession at the current time indicate that public confidence in the reports of client corporations has eroded and one way to restore this confidence could be to require ethics training of future accountants. ^

Identification of Conserved Splicing Motifs in Mutually Exclusive Exons of 15 Insect Species

Background: During alternative splicing, the inclusion of an exon in the final mRNA molecule is determined by nuclear proteins that bind cis-regulatory sequences in a target pre-mRNA molecule. A recent study suggested that the regulatory codes of individual RNA-binding proteins may be nearly immutable between very diverse species such as mammals and insects. The model system Drosophila melanogaster therefore presents an excellent opportunity for the study of alternative splicing due to the availability of quality EST annotations in FlyBase. Methods: In this paper, we describe an in silico analysis pipeline to extract putative exonic splicing regulatory sequences from a multiple alignment of 15 species of insects. Our method, ESTs-to-ESRs (E2E), uses graph analysis of EST splicing graphs to identify mutually exclusive (ME) exons and combines phylogenetic measures, a sliding window approach along the multiple alignment and the Welch’s t statistic to extract conserved ESR motifs. Results: The most frequent 100% conserved word of length 5 bp in different insect exons was “ATGGA”. We identified 799 statistically significant “spike” hexamers, 218 motifs with either a left or right FDR corrected spike magnitude p-value < 0.05 and 83 with both left and right uncorrected p < 0.01. 11 genes were identified with highly significant motifs in one ME exon but not in the other, suggesting regulation of ME exon splicing through these highly conserved hexamers. The majority of these genes have been shown to have regulated spatiotemporal expression. 10 elements were found to match three mammalian splicing regulator databases. A putative ESR motif, GATGCAG, was identified in the ME-13b but not in the ME-13a of Drosophila N-Cadherin, a gene that has been shown to have a distinct spatiotemporal expression pattern of spliced isoforms in a recent study. Conclusions: Analysis of phylogenetic relationships and variability of sequence conservation as implemented in the E2E spikes method may lead to improved identification of ESRs. We found that approximately half of the putative ESRs in common between insects and mammals have a high statistical support (p < 0.01). Several Drosophila genes with spatiotemporal expression patterns were identified to contain putative ESRs located in one exon of the ME exon pairs but not in the other.

A Case-Only Genome-wide Association Study of Gender- and Age-specific Risk Markers for Childhood Leukemia

Males and age group 1 to 5 years show a much higher risk for childhood acute lymphoblastic leukemia (ALL). We performed a case-only genome-wide association study (GWAS), using the Illumina Infinium HumanCoreExome Chip, to unmask gender- and age-specific risk variants in 240 non-Hispanic white children with ALL recruited at Texas Children’s Cancer Center, Houston, Texas. Besides statistically most significant results, we also considered results that yielded the highest effect sizes. Existing experimental data and bioinformatic predictions were used to complement results, and to examine the biological significance of statistical results. Our study identified novel risk variants for childhood ALL. The SNP, rs4813720 (RASSF2), showed the statistically most significant gender-specific associations (P < 2 x 10-6). Likewise, rs10505918 (SOX5) yielded the lowest P value (P < 1 x 10-5) for age-specific associations, and also showed the statistically most significant association with age-at-onset (P < 1 x 10-4). Two SNPs, rs12722042 and 12722039, from the HLA-DQA1 region yielded the highest effect sizes (odds ratio (OR) = 15.7; P = 0.002) for gender-specific results, and the SNP, rs17109582 (OR = 12.5; P = 0.006), showed the highest effect size for age-specific results. Sex chromosome variants did not appear to be involved in gender-specific associations. The HLA-DQA1 SNPs belong to DQA1*01:07and confirmed previously reported male-specific association with DQA1*01:07. Twenty one of the SNPs identified as risk markers for gender- or age-specific associations were located in the transcription factor binding sites and 56 SNPs were non-synonymous variants, likely to alter protein function. Although bioinformatic analysis did not implicate a particular mechanism for gender- and age-specific associations, RASSF2 has an estrogen receptor-alpha binding site in its promoter. The unknown mechanisms may be due to lack of interest in gender- and age-specificity in associations. These results provide a foundation for further studies to examine the gender- and age-differential in childhood ALL risk. Following replication and mechanistic studies, risk factors for one gender or age group may have a potential to be used as biomarkers for targeted intervention for prevention and maybe also for treatment.