Physical Sciences and Mathematics Commons^™

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.

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 …

Introducing Functional Data Analysis To Neuroimaging, And Vice Versa, Philip T. Reiss

Philip T. Reiss

No abstract provided.

Clinically Optimal Dosing In The Treatment Of Duodenal Ulcers: A Case Study Of A Phase Iii Snda Clinical Program, Karl E. Peace

Biostatistics Faculty Publications

Georgia Southern University faculty member Karl E. Peace authored "Case Study in Optimal Dosing in Duodenal Eulcer" in Peptic Ulcer Disease.

Proxy Pattern-Mixture Analysis For A Binary Variable Subject To Nonresponse., Rebecca H. Andridge, Roderick J. Little

The University of Michigan Department of Biostatistics Working Paper Series

We consider assessment of the impact of nonresponse for a binary survey

variable Y subject to nonresponse, when there is a set of covariates

observed for nonrespondents and respondents. To reduce dimensionality and

for simplicity we reduce the covariates to a continuous proxy variable X

that has the highest correlation with Y, estimated from a probit

regression analysis of respondent data. We extend our previously proposed

proxy-pattern mixture analysis (PPMA) for continuous outcomes to the binary

outcome using a latent variable approach. The method does not assume data

are missing at random, and creates a framework for sensitivity analyses.

Maximum …

A Bayesian Model For Gene Family Evolution, Liang Liu, Lili Yu, Venugopal Kalavacharla, Zhanji Liu

Biostatistics Faculty Publications

Background

A birth and death process is frequently used for modeling the size of a gene family that may vary along the branches of a phylogenetic tree. Under the birth and death model, maximum likelihood methods have been developed to estimate the birth and death rate and the sizes of ancient gene families (numbers of gene copies at the internodes of the phylogenetic tree). This paper aims to provide a Bayesian approach for estimating parameters in the birth and death model.

Results

We develop a Bayesian approach for estimating the birth and death rate and other parameters in the birth …

Depicting Estimates Using The Intercept In Meta-Regression Models: The Moving Constant Technique, Blair T. Johnson Dr., Tania B. Huedo-Medina Dr.

CHIP Documents

In any scientific discipline, the ability to portray research patterns graphically often aids greatly in interpreting a phenomenon. In part to depict phenomena, the statistics and capabilities of meta-analytic models have grown increasingly sophisticated. Accordingly, this article details how to move the constant in weighted meta-analysis regression models (viz. “meta-regression”) to illuminate the patterns in such models across a range of complexities. Although it is commonly ignored in practice, the constant (or intercept) in such models can be indispensible when it is not relegated to its usual static role. The moving constant technique makes possible estimates and confidence intervals at …

Estimation Of A Non-Parametric Variable Importance Measure Of A Continuous Exposure, Chambaz Antoine, Pierre Neuvial, Mark J. Van Der Laan

U.C. Berkeley Division of Biostatistics Working Paper Series

We define a new measure of variable importance of an exposure on a continuous outcome, accounting for potential confounders. The exposure features a reference level x0 with positive mass and a continuum of other levels. For the purpose of estimating it, we fully develop the semi-parametric estimation methodology called targeted minimum loss estimation methodology (TMLE) [van der Laan & Rubin, 2006; van der Laan & Rose, 2011]. We cover the whole spectrum of its theoretical study (convergence of the iterative procedure which is at the core of the TMLE methodology; consistency and asymptotic normality of the estimator), practical implementation, simulation …

Bland-Altman Plots For Evaluating Agreement Between Solid Tumor Measurements, Chaya S. Moskowitz, Mithat Gonen

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

Rationale and Objectives. Solid tumor measurements are regularly used in clinical trials of anticancer therapeutic agents and in clinical practice managing patients' care. Consequently studies evaluating the reproducibility of solid tumor measurements are important as lack of reproducibility may directly affect patient management. The authors propose utilizing a modified Bland-Altman plot with a difference metric that lends itself naturally to this situation and facilitates interpretation. Materials and Methods. The modification to the Bland-Altman plot involves replacing the difference plotted on the vertical axis with the relative percent change (RC) between the two measurements. This quantity is the same one used …

A Regularization Corrected Score Method For Nonlinear Regression Models With Covariate Error, David M. Zucker, Malka Gorfine, Yi Li, Donna Spiegelman

Harvard University Biostatistics Working Paper Series

No abstract provided.

Longitudinal Analysis Of Spatiotemporal Processes: A Case Study Of Dynamic Contrast-Enhanced Magnetic Resonance Imaging In Multiple Sclerosis, Russell T. Shinohara, Ciprian M. Crainiceanu, Brian S. Caffo, Daniel S. Reich

Johns Hopkins University, Dept. of Biostatistics Working Papers

Multiple sclerosis (MS) is an immune-mediated disease in which inflammatory lesions form in the brain. In many active MS lesions, the blood-brain barrier (BBB) is disrupted and blood flows into white matter; this disruption may be related to morbidity and disability. Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) allows quantitative study of blood flow and permeability dynamics throughout the brain. This technique involves a subject being imaged sequentially during a study visit as an intravenously administered contrast agent flows into the brain. In regions where flow is abnormal, such as white matter lesions, this allows the quantification of the BBB damage. …

Advancing Stage Of Female Reproductive Life Associated With Bipolar Illness Exacerbation, Wendy K. Marsh, Terence Ketter, Sybil L. Crawford, Julia V. Johnson, Anthony J. Rothschild

Sybil L. Crawford

Introduction: Perimenopause confers an increased risk of depression in the general population, yet bipolar disorder mood course remains unknown. Methods: Clinic visits in 519 premenopausal, 116 perimenopausal including 13 women transitioning from peri- to postmenopause, and 133 postmenopausal women with bipolar disorder who received naturalistic treatment in the multisite STEP-Bipolar Disorder study over 19.8 +/- 15.5 months were analyzed for mood state. Results: Advancing female reproductive stage was associated with significant decline in mood elevation; significant decline in euthymia; no significant difference in major depression; and symptomatic significant increase. Conclusions: Advancing stage of female reproductive life was associated with bipolar …

Tree-Based Methods And A Mixed Ridge Estimator For Analyzing Longitudinal Data With Correlated Predictors, Melissa Nicole Eliot

Open Access Dissertations

Due to recent advances in technology that facilitate acquisition of multi-parameter defined phenotypes, new opportunities have arisen for predicting patient outcomes based on individual specific cell subset changes. The data resulting from these trials can be a challenge to analyze, as predictors may be highly correlated with each other or related to outcome within levels of other predictor variables. As a result, applying traditional methods like simple linear models and univariate approaches such as odds ratios may be insufficient. In this dissertation, we describe potential solutions including tree-based methods, ridge regression, mixed modeling, and a new estimator called a mixed …

The Effects Of 24 Weeks Of Resistance Training With Simultaneous Elastic And Free Weight Loading On Muscular Performance Of Novice Lifters, Todd C. Shoepe, David A. Ramirez, Robert J. Rovetti, David R. Kohler, Hawley C. Almstedt

Hawley Almstedt

The purpose of this investigation was to assess the effectiveness of variable resistance as provided through elastic plus free weight techniques in college aged males and females. Twenty novice lifters were randomly assigned to a traditional free weight only (6 males and 5 females) or elastic band plus free weight group (5 males and 5 females) and 9 more normally active controls (5 males and 4 females), were recruited to maintain normal activity for the duration of the study. No differences existed between control, free weight and elastic band at baseline for age, body height, body mass, body mass index, …

The Effects Of 24 Weeks Of Resistance Training With Simultaneous Elastic And Free Weight Loading On Muscular Performance Of Novice Lifters, Todd C. Shoepe, David A. Ramirez, Robert J. Rovetti, David R. Kohler, Hawley C. Almstedt

Todd Shoepe

The purpose of this investigation was to assess the effectiveness of variable resistance as provided through elastic plus free weight techniques in college aged males and females. Twenty novice lifters were randomly assigned to a traditional free weight only (6 males and 5 females) or elastic band plus free weight group (5 males and 5 females) and 9 more normally active controls (5 males and 4 females), were recruited to maintain normal activity for the duration of the study. No differences existed between control, free weight and elastic band at baseline for age, body height, body mass, body mass index, …

Movelets: A Dictionary Of Movement, Jiawei Bai, Jeff Goldsmith, Brian Caffo, Thomas A. Glass, Ciprian M. Crainiceanu

Johns Hopkins University, Dept. of Biostatistics Working Papers

Recent technological advances provide researchers a way of gathering real-time information on an individual’s movement through the use of wearable devices that record acceleration. In this paper, we propose a method for identifying activity types, like walking, standing, and resting, from acceleration data. Our approach decomposes movements into short components called “movelets”, and builds a reference for each activity type. Unknown activities are predicted by matching new movelets to the reference. We apply our method to data collected from a single, three-axis accelerometer and focus on activities of interest in studying physical function in elderly populations. An important technical advantage …

Some Observations On The Wilcoxon Rank Sum Test, Scott S. Emerson

UW Biostatistics Working Paper Series

This manuscript presents some general comments about the Wilcoxon rank sum test. Even the most casual reader will gather that I am not too impressed with the scientific usefulness of the Wilcoxon test. However, the actual motivation is more to illustrate differences between parametric, semiparametric, and nonparametric (distribution-free) inference, and to use this example to illustrate how many misconceptions have been propagated through a focus on (semi)parametric probability models as the basis for evaluating commonly used statistical analysis models. The document itself arose as a teaching tool for courses aimed at graduate students in biostatistics and statistics, with parts of …

The Importance Of Statistical Theory In Outlier Detection, Sarah C. Emerson, Scott S. Emerson

UW Biostatistics Working Paper Series

We explore the performance of the outlier-sum statistic (Tibshirani and Hastie, Biostatistics 2007 8:2--8), a proposed method for identifying genes for which only a subset of a group of samples or patients exhibits differential expression levels. Our discussion focuses on this method as an example of how inattention to standard statistical theory can lead to approaches that exhibit some serious drawbacks. In contrast to the results presented by those authors, when comparing this method to several variations of the $t$-test, we find that the proposed method offers little benefit even in the most idealized scenarios, and suffers from a number …

Effectively Selecting A Target Population For A Future Comparative Study, Lihui Zhao, Lu Tian, Tianxi Cai, Brian Claggett, L. J. Wei

Harvard University Biostatistics Working Paper Series

When comparing a new treatment with a control in a randomized clinical study, the treatment effect is generally assessed by evaluating a summary measure over a specific study population. The success of the trial heavily depends on the choice of such a population. In this paper, we show a systematic, effective way to identify a promising population, for which the new treatment is expected to have a desired benefit, using the data from a current study involving similar comparator treatments. Specifically, with the existing data we first create a parametric scoring system using multiple covariates to estimate subject-specific treatment differences. …

Targeted Minimum Loss Based Estimation Of An Intervention Specific Mean Outcome, Mark J. Van Der Laan, Susan Gruber

U.C. Berkeley Division of Biostatistics Working Paper Series

Targeted minimum loss based estimation (TMLE) provides a template for the construction of semiparametric locally efficient double robust substitution estimators of the target parameter of the data generating distribution in a semiparametric censored data or causal inference model based on a sample of independent and identically distributed copies from this data generating distribution (van der Laan and Rubin (2006), van der Laan (2008), van der Laan and Rose (2011)). TMLE requires 1) writing the target parameter as a particular mapping from a typically infinite dimensional parameter of the probability distribution of the unit data structure into the parameter space, 2) …

Population Intervention Causal Effects Based On Stochastic Interventions, Ivan Diaz Munoz, Mark J. Van Der Laan

U.C. Berkeley Division of Biostatistics Working Paper Series

Estimating the causal effect of an intervention on a population typically involves defining parameters in a nonparametric structural equation model (Pearl, 2000, NPSEM) in which the treatment or exposure is deter- ministically assigned in a static or dynamic way. We define a new causal parameter that takes into account the fact that intervention policies can result in stochastically assigned exposures. The statistical parameter that identifies the causal parameter of interest is established. Inverse probability of treatment weighting (IPTW), augmented IPTW (A-IPTW), and targeted maximum likelihood estimators (TMLE) are developed. A simulation study is performed to demonstrate the properties of these …

Gene By Bmi Interactions Influencing C-Reactive Protein Levels In European-Americans, Sarah Tudor

Dissertations & Theses (Open Access)

C-Reactive Protein (CRP) is a biomarker indicating tissue damage, inflammation, and infection. High-sensitivity CRP (hsCRP) is an emerging biomarker often used to estimate an individual’s risk for future coronary heart disease (CHD). hsCRP levels falling below 1.00 mg/l indicate a low risk for developing CHD, levels ranging between 1.00 mg/l and 3.00 mg/l indicate an elevated risk, and levels exceeding 3.00 mg/l indicate high risk. Multiple Genome-Wide Association Studies (GWAS) have identified a number of genetic polymorphisms which influence CRP levels. SNPs implicated in such studies have been found in or near genes of interest including: CRP, APOE, APOC, IL-6, …

Bayesian Phase I Dose Finding In Cancer Trials, Lin Yang

Dissertations & Theses (Open Access)

This dissertation explores phase I dose-finding designs in cancer trials from three perspectives: the alternative Bayesian dose-escalation rules, a design based on a time-to-dose-limiting toxicity (DLT) model, and a design based on a discrete-time multi-state (DTMS) model.

We list alternative Bayesian dose-escalation rules and perform a simulation study for the intra-rule and inter-rule comparisons based on two statistical models to identify the most appropriate rule under certain scenarios. We provide evidence that all the Bayesian rules outperform the traditional ``3+3'' design in the allocation of patients and selection of the maximum tolerated dose.

The design based on a time-to-DLT model …

Prediction Of Dna Methylation Based On Genomic Architecture And Applications Of Positional Weight Matrices, Juan Gallegos

Dissertations & Theses (Open Access)

Gene silencing due to epigenetic mechanisms shows evidence of significant contributions to cancer development. We hypothesis that the genetic architecture based on retrotransposon elements surrounding the transcription start site, plays an important role in the suppression and promotion of DNA methylation. In our investigation we found a high rate of SINE and LINEs retrotransposon elements near the transcription start site of unmethylated genes when compared to methylated genes. The presence of these elements were positively associated with promoter methylation, contrary to logical expectations, due to the malicious effects of retrotransposon elements which insert themselves randomly into the genome causing possible …

A Comparison Of Spatio-Temporal Prediction Methods Of Cancer Incidence In The U.S, Michelle Hamlyn

UNLV Theses, Dissertations, Professional Papers, and Capstones

Cancer is the cause of one out of four deaths in the United States, and in 2009, researchers expected over 1.5 million new patients to be diagnosed with some form of cancer. People diagnosed with cancer, whether a common or rare type, need to undergo treatments, the amount and kind of which will depend on the severity of the cancer. So how do healthcare providers know how much funding is needed for treatment? What would better enable a pharmaceutical company to determine how much to allocate for research and development of drugs, the amount of each drug to manufacture, or …