Adaptive designs in the time to event setting: The potential for benefit and risk

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

Statistical Hurdle Models for Single Cell Gene Expression: Differential Expression and Graphical Modeling

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

Single patient (n-of-1) trials with binary treatment preference

The use of a fully parametric Bayesian method for analysing single patient trials based on the notion of treatment 'preference' is described. This Bayesian hierarchical modelling approach allows for full parameter uncertainty, use of prior information and the modelling of individual and patient sub-group structures. It provides updated probabilistic results for individual patients, and groups of patients with the same medical condition, as they are sequentially enrolled into individualized trials using the same medication alternatives. Two clinically interpretable criteria for determining a patient's response are detailed and illustrated using data from a previously published paper under two different prior information scenarios. Copyright (C) 2005 John Wiley & Sons, Ltd.

Coronary heart disease risk factors among tri-ethnic students at Florida International University

The present study identified and compared Coronary Heart Disease (CHD) risk factors quantified as “CHD risk point standards” (CHDRPS) among tri-ethnic (White non-Hispanic [WNH], Hispanic [H], and Black non-Hispanic [BNH]) college students. All 300 tri-ethnic subjects completed the Cardiovascular Risk Assessment Instruments and had blood pressure readings recorded on three occasions. The Bioelectrical Impedance Analysis (BIA) was used to measure body composition. Students' knowledge of CHD risk factors was also measured. In addition, a 15 ml fasting blood sample was collected from 180 subjects and blood lipids and Homocysteine (tHcy) levels were measured. Data were analyzed by gender and ethnicity using one-way Analysis of Variance (ANOVA) with Bonferroni's pairwise mean comparison procedure, Pearson correlation, and Chi-square test with follow-up Bonferroni's Chi-square tests. ^ The mean score of CHDRPS for all subjects was 19.15 ± 6.79. Assigned to the CHD risk category, college students were below-average risk of developing CHD. Males scored significantly (p < 0.013) higher for CHD risk than females, and BNHs scored significantly (p < 0.033) higher than WNHs. High consumption of dietary fat saturated fat and cholesterol resulted in a high CHDRPS among H males and females and WNH females. High alcohol consumption resulted in a high CHDRPS among all subjects. Mean tHcy ± SD of all subjects was 6.33 ± 3. 15 μmol/L. Males had significantly (p < 0.001) higher tHcy than females. Black non-Hispanic females and H females had significantly (p < 0.003) lower tHcy than WNH females. Positive associations were found between tHcy levels and CHDRPS among females (p < 0.001), Hs (p < 0.001), H males (p < 0.049), H females (p < 0.009), and BNH females (p < 0.005). Significant positive correlations were found between BMI levels and CHDRPS in males (p < 0.001), females (p < 0.001), WNHs (p < 0.008), Hs (p < 0.001), WNH males (p < 0.024), H males (p < 0.004) and H females (p < 0.001). The mean knowledge of CHD questions of all subjects was 71.70 ± 7.92 out of 100. The mean knowledge of CHD was significantly higher for WNH males (p < 0.039) than BNH males. A significant inverse correlation (r = 0.392, p < 0.032) was found between the CHD knowledge and CHDRPS in WNH females. The researcher's findings indicate strong gender and ethnic differences in CHD risk factors among the college-age population. ^

Statistical analysis and optimal classification of blood cell populations using Gaussian distributions

This dissertation develops a new figure of merit to measure the similarity (or dissimilarity) of Gaussian distributions through a novel concept that relates the Fisher distance to the percentage of data overlap. The derivations are expanded to provide a generalized mathematical platform for determining an optimal separating boundary of Gaussian distributions in multiple dimensions. Real-world data used for implementation and in carrying out feasibility studies were provided by Beckman-Coulter. It is noted that although the data used is flow cytometric in nature, the mathematics are general in their derivation to include other types of data as long as their statistical behavior approximate Gaussian distributions. ^ Because this new figure of merit is heavily based on the statistical nature of the data, a new filtering technique is introduced to accommodate for the accumulation process involved with histogram data. When data is accumulated into a frequency histogram, the data is inherently smoothed in a linear fashion, since an averaging effect is taking place as the histogram is generated. This new filtering scheme addresses data that is accumulated in the uneven resolution of the channels of the frequency histogram. ^ The qualitative interpretation of flow cytometric data is currently a time consuming and imprecise method for evaluating histogram data. This method offers a broader spectrum of capabilities in the analysis of histograms, since the figure of merit derived in this dissertation integrates within its mathematics both a measure of similarity and the percentage of overlap between the distributions under analysis. ^

Assessing Methods for Assigning SNPs to Genes in Gene-Based Tests of Association Using Common Variants

Gene-based tests of association are frequently applied to common SNPs (MAF>5%) as an alternative to single-marker tests. In this analysis we conduct a variety of simulation studies applied to five popular gene-based tests investigating general trends related to their performance in realistic situations. In particular, we focus on the impact of non-causal SNPs and a variety of LD structures on the behavior of these tests. Ultimately, we find that non-causal SNPs can significantly impact the power of all gene-based tests. On average, we find that the “noise” from 6–12 non-causal SNPs will cancel out the “signal” of one causal SNP across five popular gene-based tests. Furthermore, we find complex and differing behavior of the methods in the presence of LD within and between non-causal and causal SNPs. Ultimately, better approaches for a priori prioritization of potentially causal SNPs (e.g., predicting functionality of non-synonymous SNPs), application of these methods to sequenced or fully imputed datasets, and limited use of window-based methods for assigning inter-genic SNPs to genes will improve power. However, significant power loss from non-causal SNPs may remain unless alternative statistical approaches robust to the inclusion of non-causal SNPs are developed.

Evaluation of Some Statistical Methods for the Identification of Differentially Expressed Genes

Microarray platforms have been around for many years and while there is a rise of new technologies in laboratories, microarrays are still prevalent. When it comes to the analysis of microarray data to identify differentially expressed (DE) genes, many methods have been proposed and modified for improvement. However, the most popular methods such as Significance Analysis of Microarrays (SAM), samroc, fold change, and rank product are far from perfect. When it comes down to choosing which method is most powerful, it comes down to the characteristics of the sample and distribution of the gene expressions. The most practiced method is usually SAM or samroc but when the data tends to be skewed, the power of these methods decrease. With the concept that the median becomes a better measure of central tendency than the mean when the data is skewed, the tests statistics of the SAM and fold change methods are modified in this thesis. This study shows that the median modified fold change method improves the power for many cases when identifying DE genes if the data follows a lognormal distribution.

Características dos programas de residência médica em cardiologia do estado do Rio Grande do Norte

The present study had as goal to evaluate Rio Grande do Norte state’s medical residency programs (MRP) in Cardiology. It’s a descriptive study, including a documental analysis of the program’s accreditation processes (PAP) of cardiology’s medical residency in Rio Grande do Norte state in 2014 and the analysis of the resident’s perception about his professional education as a specialist in Cardiology. Beside the documental analysis of the PAPs, it was applied a semi-structured questionnaire with closed questions Likert style and open questions to all the current and former residents of the MRPs analyzed. Two MRPs in Cardiology were identified in Rio Grande do Norte state, one hosted in a public institution and the other in a private institution. The documental analysis showed a greater amount of preceptors with a good level of ownership on the public institution in comparison with the private one, as well as a bigger number of publications, participation in congresses and in book’s publications. The private institution presents a better Urgency’s infrastructure, with emergency room and cardiologic ICU. It IS clear that the residents are aware of how a good residency must work, as well as the strengths and fragilities of their own residences. Most of Onofre Lopes Universitary Hospital’s residents point out as a strength the organization, participation and quality of the preceptors, practice activities and scientific debates, great amount of patients and the visits and debates with the preceptors on the sickrooms. As the greatest fragilities, they emphasize the lack of a urgency service of their own and a specialized ICU. In Coração Hospital of Natal (HCor), it is listed as weak points the theoretic scheduling and the few ambulatory practices. As positive aspects, they report the preceptors, the agility on the execution of exams, a good number of serious patients and procedures. In both residences, it is seen a certain difficulty in accepting the important and mandatory items imposed by the rules of the Medical Residences’ National Committee, such as: biostatistics, bioethics, medical ethic, epidemiology and research methodology. Besides that, the residents recognize that both hospitals have a good infrastructure and technological support, especially in imaging methods. The evaluation of PRMCs identifies the strengths of each program and the aspects to be improved in both programs. It also allowed the observation of difficulties in accepting some regulations contained in the CNRM resolution by the resident, such as participation in activities such as biostatistics, epidemiology and research methodology as well as the improvement needs of specific technical training, such as in emergency care. Thus, our results make possible to develop strategies for continued improvement of PRMC in RN state. In addition, it enabled the preparation of the resident’s manual in cardiology, containing even a breakdown of resident evaluation system, which could serve as a model for other residency programs.

Evaluating statistical and machine learning methods to predict risk of in-hospital child mortality in Uganda

Thesis (Master's)--University of Washington, 2016-08

Data-Adaptive Modeling using Convex Regression

Thesis (Ph.D.)--University of Washington, 2016-08

Recovering Natural History: Modeling Cardiovascular Biomarkers in the Presence of Endogenous Medication Use

Thesis (Ph.D.)--University of Washington, 2016-08

Methods for Hypothesis Testing in Animal Carcinogenicity Experiments

Thesis (Ph.D.)--University of Washington, 2016-08

Stepped Wedge Design for Multiple Interventions

Thesis (Master's)--University of Washington, 2016-08

Searching for Predictive Subgroups

Thesis (Ph.D.)--University of Washington, 2016-08