Biostatistics Commons^™

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 …

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, …

Incorporating Network Structure In Integrative Analysis Of Cancer Prognosis Data, Shuangge Ma

Shuangge Ma

In high-throughput cancer genomic studies, markers identified from the analysis of single datasets may have unsatisfactory properties because of low sample sizes. Integrative analysis pools and analyzes raw data from multiple studies, and can effectively increase sample size and lead to improved marker identification results. In this study, we consider the integrative analysis of multiple high-throughput cancer prognosis studies. In the existing integrative analysis studies, the interplay among genes, which can be described using the network structure, has not been effectively accounted for. In network analysis, tightly-connected nodes (genes) are more likely to have related biological functions and similar regression …

Risk Factors Of Follicular Lymphoma, Shuangge Ma

Shuangge Ma

No abstract provided.

Health Insurance Coverage And Impact: A Survey In Three Cities In China, Shuangge Ma

Shuangge Ma

No abstract provided.

Integrative Analysis Of Multiple Cancer Genomic Datasets Under The Heterogeneity Model, Shuangge Ma

Shuangge Ma

No abstract provided.

Health Insurance Coverage, Medical Expenditure And Coping Strategy: Evidence From Taiwan, Shuangge Ma

Shuangge Ma

No abstract provided.

Impact Of Illness And Medical Expenditure On Household Consumptions: A Survey In Western China, Shuangge Ma

Shuangge Ma

No abstract provided.

Identification Of Gene-Environment Interactions In Cancer Prognosis Studies Using Penalization, Shuangge Ma

Shuangge Ma

High-throughput cancer studies have been extensively conducted, searching for genetic risk factors independently associated with prognosis beyond clinical and environmental risk factors. Many studies have shown that the gene-environment interactions may have important implications. Some of the existing methods, such as the commonly adopted single-marker analysis, may be limited in that they cannot accommodate the joint effects of a large number of genetic markers or use ineffective marker identification techniques. In this study, we analyze cancer prognosis studies, and adopt the AFT (accelerated failure time) model to describe survival. A weighted least squares approach, which has the lowest computational cost, …

Adaptive Matching In Randomized Trials And Observational Studies, M. Van Der Laan, Laura Balzer, M. Petersen

Laura B. Balzer

Resampling-Based Information Criteria For Best-Subset Regression, Philip T. Reiss, Lei Huang, Joseph E. Cavanaugh, Amy Krain Roy

Philip T. Reiss

When a linear model is chosen by searching for the best subset among a set of candidate predictors, a fixed penalty such as that imposed by the Akaike information criterion may penalize model complexity inadequately, leading to biased model selection. We study resampling-based information criteria that aim to overcome this problem through improved estimation of the effective model dimension. The first proposed approach builds upon previous work on bootstrap-based model selection. We then propose a more novel approach based on cross-validation. Simulations and analyses of a functional neuroimaging data set illustrate the strong performance of our resampling-based methods, which are …

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.

Adjusting Medicare Capitation Payments Using Prior Hospitalization Data, Arlene Ash, Frank Porell, Leonard Gruenberg, Eric Sawitz, Alexa Beiser

Frank Porell

The diagnostic cost group approach to a reimbursement model for health maintenance organizations is presented. Diagnostic information about previous hospitalizations is used to create empirically determined risk groups, using only diagnoses involving little or no discretion in the decision to hospitalize. Diagnostic cost group and other models (including Medicare's current formula and other prior-use models) are tested for their ability to predict future costs, using R2 values and new measures of predictive performance. The diagnostic cost group models perform relatively well with respect to a range of criteria, including administrative feasibility, resistance to provider manipulation, and statistical accuracy.

Geographic Disparities Associated With Stroke And Myocardial Infarction In East Tennessee, Ashley Pedigo Golden

Doctoral Dissertations

Stroke and myocardial infarction (MI) are serious conditions whose burdens vary by socio-demographic and geographic factors. Although several studies have investigated and identified disparities in burdens of these conditions at the county and state levels, little is known regarding their geographic epidemiology at the neighborhood level. Both conditions require emergency treatments and therefore timely geographic accessibility to appropriate care is critical. Investigation of disparities in geographic accessibility to stroke and MI care and the role of Emergency Medical Services (EMS) in reducing treatment delays are vital in improving health outcomes. Therefore, the objectives of this work were to: (i) classify …

An Analysis Of Breast Cancer Metastasis, Jennifer Lee Gildner

Statistics

The main objective of this paper is to evaluate possible socio-economic status, clinical, and treatment associations with the occurrence of distant metastasis in Stage I – III breast cancer patients. After analysis in a logistic regression model, four variables were found to be significant with occurrence of distant metastases. These variables were: education, disease group (Triple-negative, Her2Neu-positive and Luminal A), stage at diagnosis, and concordance to chemotherapy based on the NCCN guidelines. Patients without a college degree were found to be more likely to develop distant metastasis than those with a college degree (OR = 2.46 95% CI 1.44 – …

Time-Dependent Cortical Activation In Voluntary Muscle Contraction, Qi Yang, Xiao-Feng Wang, Yin Fang, Vlodek Siemionow, Wanxiang Yao, Guang H. Yue

Xiaofeng Wang

This study was to characterize dynamic source strength changes estimated from high-density scalp electroencephalogram (EEG) at different phases of a submaximal voluntary muscle contraction. Eight healthy volunteers performed isometric handgrip contractions of the right arm at 20% maximal intensity. Signals of the handgrip force, electromyography (EMG) from the finger flexor and extensor muscles and 64-channel EEG were acquired simultaneously. Sources of the EEG were analyzed at 19 time points across preparation, execution and sustaining phases of the handgrip. A 3-layer boundary element model (BEM) based on the MNI (Montréal Neurological Institute) brain MRI was used to overlay the sources. A …

Development Of A Bayesian Joint Logistic Model To Better Study The Association Between Haplotypes And Disease, Anthony M. D'Amelio Jr

Dissertations & Theses (Open Access)

In 2011, there will be an estimated 1,596,670 new cancer cases and 571,950 cancer-related deaths in the US. With the ever-increasing applications of cancer genetics in epidemiology, there is great potential to identify genetic risk factors that would help identify individuals with increased genetic susceptibility to cancer, which could be used to develop interventions or targeted therapies that could hopefully reduce cancer risk and mortality.

In this dissertation, I propose to develop a new statistical method to evaluate the role of haplotypes in cancer susceptibility and development. This model will be flexible enough to handle not only haplotypes of any …

Testing For Improvement In Prediction Model Performance, Margaret S. Pepe Phd, Kathleen F. Kerr Phd, Gary Longton, Zheyu Wang Phd

Margaret S Pepe PhD

New methodology has been proposed in recent years for evaluating the improvement in prediction performance gained by adding a new predictor, Y, to a risk model containing a set of baseline predictors, X, for a binary outcome D. We prove theoretically that null hypotheses concerning no improvement in performance are equivalent to the simple null hypothesis that the coefficient for Y is zero in the risk model, P(D=1|X,Y). Therefore, testing for improvement in prediction performance is redundant if Y has already been shown to be a risk factor. We investigate properties of tests through simulation studies, focusing on the change …

Exploration And Comparison Of Methods For Combining Population- And Family-Based Genetic Association Using The Genetic Analysis Workshop 17 Mini-Exome, David W. Fardo, Anthony R. Druen, Jinze Liu, Lucia Mirea, Claire Infante-Rivard, Patrick Breheny

Biostatistics Faculty Publications

We examine the performance of various methods for combining family- and population-based genetic association data. Several approaches have been proposed for situations in which information is collected from both a subset of unrelated subjects and a subset of family members. Analyzing these samples separately is known to be inefficient, and it is important to determine the scenarios for which differing methods perform well. Others have investigated this question; however, no extensive simulations have been conducted, nor have these methods been applied to mini-exome-style data such as that provided by Genetic Analysis Workshop 17. We quantify the empirical power and false-positive …