Objective. to determine how patterns of respiratory symptom change, patient behavior, and health status are related among patients with chronic obstructive pulmonary disease (COPD) and a history of exacerbations. Methods. The study population was 421 community-dwelling adults with moderate to severe COPD. Symptom-based events (exacerbations) were defined to be any increase in at least one key symptom (dyspnea, sputum amount, sputum color) recorded in the daily diary on at least two consecutive days. An event was reported if it resulted in an exacerbation phone call or documented health-care utilization. Predictors of reporting were assessed using a Cox proportional hazards model. Results. Two-thirds of all events and 40% of events with 4 or more symptoms were not reported. Reporting an event was positively associated with a greater number of respiratory symptoms (HR:1.58, 95% CI: 1.37-1.81), a younger age (HR:1.12, 95% Cl:1.02-1.22 each 5 years), a lower FEV1 (HR:1.20, 95% CI:1.01-1.43 each 10% of predicted FEV1), and weekdays versus weekend (HR:3.03 and 95% CI:1.89-4.76). Conclusion. There was a high incidence of unreported exacerbations and some were important enough (4 or more symptoms) to have an indication for treatment. Reporting was related to the severity of exacerbation and underlying disease.

<p> This work presents a novel size-structured model to mathematically describe the transmission dynamics of <i>Mycobacterium marinum</i> in an aquatic environment. Biological background on the formation of the model is discussed in Chapter 1. In Chapter 2, the model is developed and consisted of a system on nonlinear partial differential equations coupled to three nonlinear ordinary differential equations. The weak solution is defined and current numerical work on structured models is discussed.</p><p> In Chapter 3, a first-order method is developed to approximate the solution to the model, and in Chapter 4, a second-order high resolution method is developed. Theoretical foundations for both methods are established. Also, convergence to the unique weak solution is verified for both methods.</p><p> In Chapters 3 and 4, the numerical results begin with showing each method is in fact of the appropriate order for a simple version of the model, and then with the full nonlinear version. Chapter 3 continues the numerical results section with preliminary studies on the key features of this model, such as various forms of growth rates (indicative of possible theories of development), and conditions for competitive exclusion or coexistence as determined by reproductive fitness and genetic spread in the population. In Chapter 4, we compare the first and second-order methods to show the computational benefits that come with a second-order method. We also demonstrate that the model can be a tool to understand surprising or nonintuitive phenomena regarding competitive advantage in the context of biologically realistic growth, birth, and death rates.</p>

<p> Community-acquired urinary tract infections (CA-UTI) are common in young women. Reports of increasing resistance to the antimicrobial drugs commonly prescribed to treat CA-UTI, evidence of wide-spread dissemination of strains of multi-drug resistant i that can cause community outbreaks and expanding appreciation of the importance of the rational use of antibiotics are challenging the traditional management of this disease. </p><p> Two population-based studies were performed to investigate the epidemiological features of CA-UTI with an emphasis on the antimicrobial resistance of causative bacteria. An eight-year retrospective cohort study was conducted in a large health maintenance organization to identify changes in uropathogen etiology and antimicrobial resistance and in empirical antimicrobial treatment practices and outcomes. A cross-sectional study was performed in a university population to investigate the relationship between changes in the prevalence of genotype-based clonal groups of uropathogen E. coli and the prevalence of antimicrobial resistance. </p><p> From 1998 through 2005, less than 20% of the <i>Escherichia coli </i> causing uncomplicated CA-UTI (UCA-UTI) were resistant to the first line empirical treatment antimicrobial, trimethoprim/sulfamethoxazole (TMP/SMX). No trends were detected in the proportions of <i>Escherichia coli</i> that were resistant to TMP/SMX or to nitrofurantoin. In contrast, a small but steady increase in the proportion of Escherichia coli that were resistant to ciprofloxacin was observed. Over the same period of time, the use of ciprofloxacin as empirical treatment for UCA-UTI steadily increased while the use of TMP/SMX decreased. No sustained decreases in treatment failure or in microbiologically incompatible treatment were detected. Thus TMP/SMX remains a viable empirical treatment for women with UCA- UTI in these populations. Molecular typing of Escherichia coli causing CA-UTI revealed that the prevalence of antimicrobial resistance was influenced by a small number of <i>Escherichia coli</i> clonal groups. This suggests that the prevalence of antimicrobial resistant UTI in a community is not only the result of community prescribing practices and individual antimicrobial use but can be significantly impacted by the introduction and circulation of strains of uropathogens that are already drug resistant. Thus, strategies developed to maintain the usefulness of empirical treatment options for CA-UTI must include interventions that target sources of antimicrobial resistant uropathogens.</p>

The course and prognosis of childhood onset multiple sclerosis (MS) is not well defined unlike that with adult onset. / A cohort of 380 patients with childhood onset (before the age of 16) MS and 3367 with adult onset were identified through the European Database for Multiple Sclerosis. The median time to reaching scores of four and six on the disability status scale was longer for childhood onset MS patients (20 and 29 years) compared with adult onset patients (12.8 and 23.7 years; p&lt;0.0001). Two years after onset, the main prognostic factors of disability in childhood onset MS patients were age at onset, gender and the number of relapses during the first two years of MS. We showed that immortal time bias explains the previously reported protective effect of the time between the first two relapses on disability. / Childhood onset MS has a slower evolution to disability than adult onset MS.

Thesis (Ph.D.)--University of California, San Francisco, 2008. / Source: Dissertation Abstracts International, Volume: 69-09, Section: B, page: 5181. Adviser: Esteban G. Burchard.

Thesis (Ph.D.)--University of Cincinnati, 2007. / (UMI)AAI3295391. Source: Dissertation Abstracts International, Volume: 68-12, Section: B, page: 7905. Adviser: Kim N. Dietrich.

Thesis (Ph.D.)--University of Illinois at Urbana-Champaign, 2006. / Source: Dissertation Abstracts International, Volume: 67-07, Section: B, page: 3676. Adviser: Uriel D. Kitron. Includes bibliographical references. Available on microfilm from Pro Quest Information and Learning.

In this dissertation, we first assess the associations between circulating metabolites and body mass index in two U.S. prospective cohorts. Then, we propose several methods to analyze multiple phenotypes in genetic association studies based on summary statistics. In the Chapter 1, we investigate the associations between circulating metabolites and repeatedly measured body mass index (BMI) among Caucasian men and women. We employed linear mixed models with a random intercept term to account for the within-subject correlation and adjust for potential baseline confounders including baseline obesity status, smoking, physical activity, alcohol intake, total caloric intake, age at blood draw and follow-up years. We didn't find the associations were heterogeneous between Caucasian men and women, and therefore we used fixed effect meta-analysis to combine evidences of associations from these two cohorts. We found that valine, leucine and isoleucine were positively associated with BMI, while acetylglycine was negatively associated with BMI. In Chapter 2, we present linear mixed model based score tests for the detection of pleotropic genetic variants that are associated with multiple correlated traits based on summary statistics. Our tests are robust to effect heterogeneity and correlation structures among multiple traits. We conducted simulation studies to compare the proposed methods with existing methods. We also applied our methods to a global lipids GWAS summary statistics data set and identified hundreds of novel genetic variants. In Chapter 3, we propose a geometric perspective on the powers of principal component association tests based on GWAS summary statistics. Utilizing eigen-analysis of the correlation matrix and asymptotic power analysis, we investigate when PCA is powerful and when it is not to detect the genetic signals. We further apply our methods to a global lipids level genome-wide association study data set and identify hundreds of novel genetic variants that were missed by conventional single-trait analysis approaches. Our results can help guide researchers to choose powerful PCAT methods in multiple phenotype association studies and also better interpret the association results. / Epidemiology

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