Biostatistics Commons^™

Statistical Methods For Normalization And Analysis Of High-Throughput Genomic Data, Tobias Guennel

Theses and Dissertations

High-throughput genomic datasets obtained from microarray or sequencing studies have revolutionized the field of molecular biology over the last decade. The complexity of these new technologies also poses new challenges to statisticians to separate biological relevant information from technical noise. Two methods are introduced that address important issues with normalization of array comparative genomic hybridization (aCGH) microarrays and the analysis of RNA sequencing (RNA-Seq) studies. Many studies investigating copy number aberrations at the DNA level for cancer and genetic studies use comparative genomic hybridization (CGH) on oligo arrays. However, aCGH data often suffer from low signal to noise ratios resulting …

A Systematic Selection Method For The Development Of Cancer Staging Systems, Yunzhi Lin, Richard Chappell, Mithat Gonen

Memorial Sloan-Kettering Cancer Center, Dept. of Epidemiology & Biostatistics Working Paper Series

The tumor-node-metastasis (TNM) staging system has been the anchor of cancer diagnosis, treatment, and prognosis for many years. For meaningful clinical use, an orderly, progressive condensation of the T and N categories into an overall staging system needs to be defined, usually with respect to a time-to-event outcome. This can be considered as a cutpoint selection problem for a censored response partitioned with respect to two ordered categorical covariates and their interaction. The aim is to select the best grouping of the TN categories. A novel bootstrap cutpoint/model selection method is proposed for this task by maximizing bootstrap estimates of …

On Identification Of Natural Direct Effects When A Confounder Of The Mediator Is Directly Affected By Exposure, Eric J. Tchetgen Tchetgen, Tyler J. Vanderweele

Harvard University Biostatistics Working Paper Series

No abstract provided.

Analysis Of Periodontal Data Using Circular Statistics, Samopriyo Maitra, Thomas M. Braun

The University of Michigan Department of Biostatistics Working Paper Series

Periodontal disease is a common cause of tooth loss in adults. The severity of periodontal disease is usually quantified based upon the magnitudes of several tooth-level clinical parameters, the most common of which is clinical attachment level (CAL). Re- cent clinical studies have presented data on the distribution of periodontal disease in hopes of providing information for localized treatments that can reduce the prevalence of periodontal disease. However, these findings have been descriptive without consid- eration of statistical modeling for estimation and inference. To this end, we visualize the mouth as a circle and the teeth as points located on …

The Bayesian Continual Reassessment Method Using A Mixture-Of-Uniforms Prior, Thomas M. Braun

The University of Michigan Department of Biostatistics Working Paper Series

Traditionally, the Bayesian formulation of the Continual Reassessment Method (CRM) is implemented with a one-parameter model describing the association of dose with the probability of dose-limiting toxicity (DLT). Determination of the appropriate value of the prior variance is often done via simulation over a grid search of possible values until suitable operating characteristics are found. However, it is under-appreciated that the operating characteristics for a given value of the prior variance vary by the “skeleton,” which is the vector of a priori probabilities of DLT for each dose. The skeleton implicitly leads to a set of indifference intervals, with one …

Hypothesis Testing And Power Calculations For Taxonomic-Based Human Microbiome Data, P. S. Larossa, J. Paul Brooks, Elena Deych, Edward L. Boone, David J. Edwards, Qin Wang, Erica Sodergren, George Weinstock, William D. Shannon

Statistical Sciences and Operations Research Publications

This paper presents new biostatistical methods for the analysis of microbiome data based on a fully parametric approach using all the data. The Dirichlet-multinomial distribution allows the analyst to calculate power and sample sizes for experimental design, perform tests of hypotheses (e.g., compare microbiomes across groups), and to estimate parameters describing microbiome properties. The use of a fully parametric model for these data has the benefit over alternative non-parametric approaches such as bootstrapping and permutation testing, in that this model is able to retain more information contained in the data. This paper details the statistical approaches for several tests of …

Aspirin But Not Ibuprofen Use Is Associated With Reduced Risk Of Prostate Cancer: A Plco Study, F. M. Shebl, L. C. Sakoda, A. Black, J. Koziol, G. L. Andriole, R. Grubb, T. R. Church, D. Chia, Cindy Zhou, +8 Additional Authors

GW Biostatistics Center

Background:

Although most epidemiological studies suggest that non-steroidal anti-inflammatory drug use is inversely associated with prostate cancer risk, the magnitude and specificity of this association remain unclear.

Methods:

We examined self-reported aspirin and ibuprofen use in relation to prostate cancer risk among 29 450 men ages 55–74 who were initially screened for prostate cancer from 1993 to 2001 in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. Men were followed from their first screening exam until 31 December 2009, during which 3575 cases of prostate cancer were identified.

Results:

After adjusting for potential confounders, the hazard ratios (HRs) of …

Association Between Chemical Constituents Of Particulate Matter And Cardiovascular And Respiratory Morbidities In Nys, Rena Jones

Legacy Theses & Dissertations (2009 - 2024)

Improved understanding of health risks from short- and long-term exposure to fine particulate matter (PM_2.5) constituents may explain seasonal and geographic heterogeneity in PM_{2.5-health associations and inform control efforts targeting PM sources. Few studies have examined PM species health effects; most have been limited by their exposure assessments and modeling approaches. The goals of this project were to improve the PM exposure assessment and explore relationships between PM2.5 species and health in acute and chronic contexts.}

Alternatives To Mixture Model Analysis Of Correlated Binomial Data, N. Rao Chaganty, Roy Sabo, Yihao Deng

Mathematics & Statistics Faculty Publications

While univariate instances of binomial data are readily handled with generalized linear models, cases of multivariate or repeated measure binomial data are complicated by the possibility of correlated responses. Likelihood-based estimation can be applied by using mixture distribution models, though this approach can present computational challenges. The logistic transformation can be used to bypass these concerns and allow for alternative estimating procedures. One popular alternative is the generalized estimating equation (GEE) method, though systematic errors can lead to infeasible correlation estimates or nonconvergence problems. Our approach is the coupling of quasileast squares (QLSs) method with a rarely used matrix factorization, …

The Cumulative Impact Of Unemployment On Risks Of Acute Myocardial Infarction, Guangya Liu, Matthew E. Dupree, Linda K. George, Eric D. Peterson

Faculty Scholarship

Background: Employment instability is a major source of strain affecting an increasing number of adults in the United States. Little is known about the cumulative effect of multiple job losses and unemployment on the risks for acute myocardial infarction (AMI).

Methods: We investigated the associations between different dimensions of unemployment and the risks for AMI in US adults in a prospective cohort study of adults (N=13 451) aged 51 to 75 years in the Health and Retirement Study with biennial follow-up interviews from 1992 to 2010. Unadjusted rates of age-specific AMI were used to demonstrate observed differences by employment status, …

The Analysis Of Image Feature Robustness Using Cometcloud, Xin Qi, Hyunjoo Kim, Fuyong Xing, Manish Parashar, David J. Foran, Lin Yang

Biostatistics Faculty Publications

The robustness of image features is a very important consideration in quantitative image analysis. The objective of this paper is to investigate the robustness of a range of image texture features using hematoxylin stained breast tissue microarray slides which are assessed while simulating different imaging challenges including out of focus, changes in magnification and variations in illumination, noise, compression, distortion, and rotation. We employed five texture analysis methods and tested them while introducing all of the challenges listed above. The texture features that were evaluated include co-occurrence matrix, center-symmetric auto-correlation, texture feature coding method, local binary pattern, and texton. Due …

Analysis Of Binary Data Via Spatial-Temporal Autologistic Regression Models, Zilong Wang

Theses and Dissertations--Statistics

Spatial-temporal autologistic models are useful models for binary data that are measured repeatedly over time on a spatial lattice. They can account for effects of potential covariates and spatial-temporal statistical dependence among the data. However, the traditional parametrization of spatial-temporal autologistic model presents difficulties in interpreting model parameters across varying levels of statistical dependence, where its non-negative autocovariates could bias the realizations toward 1. In order to achieve interpretable parameters, a centered spatial-temporal autologistic regression model has been developed. Two efficient statistical inference approaches, expectation-maximization pseudo-likelihood approach (EMPL) and Monte Carlo expectation-maximization likelihood approach (MCEML), have been proposed. Also, Bayesian …

Evaluating Retention In Medical Care And Its Impact On The Health Outcomes Of Individuals Living With Human Inmmunodeficiency Virus, Timothy N. Crawford

Theses and Dissertations--Epidemiology and Biostatistics

In the last few years, engagement in medical care among individuals living with HIV has become a major priority among HIV medical providers and public health researchers. Engagement in medical care is an important concept as it involves the process of linking newly diagnosed individuals into medical care and retaining those individuals in care throughout the course of their infection. Although there have been major advances in the management of HIV, like the advent of Highly Active Antiretroviral Therapy, morbidity and mortality due to HIV cannot be fully reduced if the individual does not optimally retain in care. Retention in …

Secondary Structure Prediction Of Long Rna Sequences Based On Inversion Excursions And A Modularized Mapreduce Framework, Daniel Tesfai Yehdego

Open Access Theses & Dissertations

Ribonucleic acid (RNA) molecules and their secondary structures play important roles in many biological processes including gene expression and regulation. The genomes of many viruses are also RNA molecules. Since secondary structures are crucial for RNA functionality, computational predictions of the RNA secondary structures have been widely studied. However, the tremendous demands on computer memory and computing time for complex secondary structures limit the capability of existing thermodynamically based algorithms for structure predictions to handling only short RNA sequences with a few hundred bases. One approach to overcome this limitation is by first cutting long RNA sequences into shorter, non-overlapping …

Generalized Linear Latent Mixed Modeling Of Functional Independent Measures And Patient Outcomes, Maduranga Kasun Dassanayake

Open Access Theses & Dissertations

The Functional Independent Measure (FIM) is one of the most widely accepted functional assessment measures used in the rehabilitation community. Past research studies have investigated the relationship between place of discharge, admission FIM scores or FIM difference scores, and patients' characteristics and found relationships between those variables. However, most of these studies fail to account for the multi-layered multidimensionality of the FIM and the measurement error associated with the FIM items. This study utilizes Generalized Linear Latent Mixed Models (GLLAMM) and Structural Equation Models (SEM) to assess which patient characteristics are associated with FIM difference scores and the structural relationship …

Bayesian Inference On Mixed-Effects Models With Skewed Distributions For Hiv Longitudinal Data, Ren Chen

USF Tampa Graduate Theses and Dissertations

Statistical models have greatly improved our understanding of the pathogenesis of HIV-1 infection

and guided for the treatment of AIDS patients and evaluation of antiretroviral (ARV) therapies.

Although various statistical modeling and analysis methods have been applied for estimating the

parameters of HIV dynamics via mixed-effects models, a common assumption of distribution is

normal for random errors and random-effects. This assumption may lack the robustness against

departures from normality so may lead misleading or biased inference. Moreover, some covariates

such as CD4 cell count may be often measured with substantial errors. Bivariate clustered

(correlated) data are also commonly encountered in …

Linear Mixed-Effects Models: Applications To The Behavioral Sciences And Adolescent Community Health, Lizmarie Gabriela Maldonado

USF Tampa Graduate Theses and Dissertations

Linear mixed-effects (LME) modeling is a widely used statistical method for analyzing repeated measures or longitudinal data. Such longitudinal studies typically aim to investigate and describe the trajectory of a desired outcome. Longitudinal data have the advantage over cross-sectional data by providing more accuracy for the model. LME models allow researchers to account for random variation among individuals and between individuals.

In this project, adolescent health was chosen as a topic of research due to the many changes that occur during this crucial time period as a precursor to overall well-being in adult life. Understanding the factors that influence how …

Statistical Estimation Of Physiologically-Based Pharmacokinetic Models: Identifiability, Variation, And Uncertainty With An Illustration Of Chronic Exposure To Dioxin And Dioxin-Like-Compounds., Zachary John Thompson

USF Tampa Graduate Theses and Dissertations

Assessment of human exposure to environmental chemicals is inherently subject to uncertainty and variability. There are data gaps concerning the inventory, source, duration, and intensity of exposure

as well as knowledge gaps regarding pharmacokinetics in general. These gaps result in uncertainties in exposure assessment.

The uncertainties compound further with variabilities due to population variations regarding stage of life, life style, and susceptibility,

etc. Use of physiologically-based pharmacokinetic (PBPK) models promises to reduce the uncertainties and enhance extrapolation between species, between routes, from high to low dose, and from acute to chronic exposure. However, fitting PBPK models is challenging because of …

Evaluation Of Repeated Biomarkers: Non-Parametric Comparison Of Areas Under The Receiver Operating Curve Between Correlated Groups Using An Optimal Weighting Scheme, Ping Xu

USF Tampa Graduate Theses and Dissertations

Receiver Operating Characteristic (ROC) curves are often used to evaluate the prognostic performance of a continuous biomarker. In a previous research, a non-parametric ROC approach was introduced to compare two biomarkers with repeated measurements. An asymptotically normal statistic, which contains the subject-specific weights, was developed to estimate the areas under the ROC curve of biomarkers. Although two weighting schemes were suggested to be optimal when the within subject correlation is 1 or 0 by the previous study, the universal optimal weight was not determined. We modify this asymptotical statistic to compare AUCs between two correlated groups and propose a solution …

Flexible Distributed Lag Models Using Random Functions With Application To Estimating Mortality Displacement From Heat-Related Deaths, Roger D. Peng

Johns Hopkins University, Dept. of Biostatistics Working Papers

No abstract provided.