Medicine and Health Sciences Commons^™

Bayesian Prediction Intervals For Assessing P-Value Variability In Prospective Replication Studies, Olga A. Vsevolozhskaya, Gabriel Ruiz, Dmitri Zaykin

Biostatistics Faculty Publications

Increased availability of data and accessibility of computational tools in recent years have created an unprecedented upsurge of scientific studies driven by statistical analysis. Limitations inherent to statistics impose constraints on the reliability of conclusions drawn from data, so misuse of statistical methods is a growing concern. Hypothesis and significance testing, and the accompanying P-values are being scrutinized as representing the most widely applied and abused practices. One line of critique is that P-values are inherently unfit to fulfill their ostensible role as measures of credibility for scientific hypotheses. It has also been suggested that while P-values …

Systems Biology Approach To Late-Onset Alzheimer's Disease Genome-Wide Association Study Identifies Novel Candidate Genes Validated Using Brain Expression Data And Caenorhabditis Elegans Experiments, Shubhabrata Mukherjee, Joshua C. Russell, Daniel T. Carr, Jeremy D. Burgess, Mariet Allen, Daniel J. Serie, Kevin L. Boehme, John S. K. Kauwe, Adam C. Naj, David W. Fardo, Dennis W. Dickson, Thomas J. Montine, Nilufer Ertekin-Taner, Matt R. Kaeberlein, Paul K. Crane

Biostatistics Faculty Publications

Introduction—We sought to determine whether a systems biology approach may identify novel late-onset Alzheimer's disease (LOAD) loci.

Methods—We performed gene-wide association analyses and integrated results with human protein-protein interaction data using network analyses. We performed functional validation on novel genes using a transgenic Caenorhabditis elegans Aβ proteotoxicity model and evaluated novel genes using brain expression data from people with LOAD and other neurodegenerative conditions.

Results—We identified 13 novel candidate LOAD genes outside chromosome 19. Of those, RNA interference knockdowns of the C. elegans orthologs of UBC, NDUFS3, EGR1, and ATP5H were associated with Aβ …

Judging The Neonatal Abstinence Syndrome Assessment Tools To Guide Future Tool Development: The Use Of Clinimetrics As Opposed To Psychometrics, Philip M. Westgate, Enrique Gomez-Pomar

Biostatistics Faculty Publications

In the face of the current Neonatal Abstinence Syndrome (NAS) epidemic, there is considerable variability in the assessment and management of infants with NAS. In this manuscript, we particularly focus on NAS assessment, with special attention given to the popular Finnegan Neonatal Abstinence Score (FNAS). A major instigator of the problem of variable practices is that multiple modified versions of the FNAS exist and continue to be proposed, including shortened versions. Furthermore, the validity of such assessment tools has been questioned, and as a result, the need for better tools has been suggested. The ultimate purpose of this manuscript, therefore, …

Impact Of Home Visit Capacity On Genetic Association Studies Of Late-Onset Alzheimer's Disease, David W. Fardo, Laura E. Gibbons, Shubhabrata Mukherjee, M. Maria Glymour, Wayne Mccormick, Susan M. Mccurry, James D. Bowen, Eric B. Larson, Paul K. Crane

Biostatistics Faculty Publications

INTRODUCTION—Findings for genetic correlates of late-onset Alzheimer's disease (LOAD) in studies that rely solely on clinic visits may differ from those with capacity to follow participants unable to attend clinic visits.

METHODS—We evaluated previously identified LOAD-risk single nucleotide variants in the prospective Adult Changes in Thought study, comparing hazard ratios (HRs) estimated using the full data set of both in-home and clinic visits (n = 1697) to HRs estimated using only data that were obtained from clinic visits (n = 1308). Models were adjusted for age, sex, principal components to account for ancestry, and additional health indicators.

RESULTS …

Peripheral Inflammation, Apolipoprotein E4, And Amyloid-Β Interact To Induce Cognitive And Cerebrovascular Dysfunction, Felecia M. Marottoli, Yuriko Katsumata, Kevin P. Koster, Riya Thomas, David W. Fardo, Leon M. Tai

Biostatistics Faculty Publications

Cerebrovascular dysfunction is rapidly reemerging as a major process of Alzheimer’s disease (AD). It is, therefore, crucial to delineate the roles of AD risk factors in cerebrovascular dysfunction. While apolipoprotein E4 (APOE4), Amyloid-β (Aβ), and peripheral inflammation independently induce cerebrovascular damage, their collective effects remain to be elucidated. The goal of this study was to determine the interactive effect of APOE4, Aβ, and chronic repeated peripheral inflammation on cerebrovascular and cognitive dysfunction in vivo. EFAD mice are a well-characterized mouse model that express human APOE3 (E3FAD) or APOE4 (E4FAD) and overproduce human Aβ42 via expression of …

Estimated Probability Of Becoming A Case Of Drug Dependence In Relation To Duration Of Drug-Taking Experience: A Functional Analysis Approach, Olga A. Vsevolozhskaya, James C. Anthony

Biostatistics Faculty Publications

Measured as elapsed time from first use to dependence syndrome onset, the estimated "induction interval" for cocaine is thought to be short relative to the cannabis interval, but little is known about risk of becoming dependent during first months after onset of use. Virtually all published estimates for this facet of drug dependence epidemiology are from life histories elicited years after first use. To improve estimation, we turn to new month-wise data from nationally representative samples of newly incident drug users identified via probability sampling and confidential computer-assisted self-interviews for the United States National Surveys on Drug Use and Health, …

Tuberculosis And Risk Of Acute Myocardial Infarction: A Propensity Score-Matched Analysis, Moises A. Huaman, Richard J. Kryscio, Carl J. Fichtenbaum, David Henson, Elizabeth G. Salt, Timothy R. Sterling, Beth A. Garvy

Biostatistics Faculty Publications

Several pathogens have been associated with increased cardiovascular disease (CVD) risk. Whether this occurs with Mycobacterium tuberculosis infection is unclear. We assessed if tuberculosis disease increased the risk of acute myocardial infarction (AMI). We identified patients with tuberculosis index claims from a large de-identified database of ~15 million adults enrolled in a U.S. commercial insurance policy between 2008 and 2010. Tuberculosis patients were 1:1 matched to patients without tuberculosis claims using propensity scores. We compared the occurrence of index AMI claims between the tuberculosis and non-tuberculosis cohorts using Kaplan–Meier curves and Cox Proportional Hazard models. Data on 2026 patients with …

Identification Of Prognostic Genes And Gene Sets For Early-Stage Non-Small Cell Lung Cancer Using Bi-Level Selection Methods, Suyan Tian, Chi Wang, Howard H. Chang, Jianguo Sun

Biostatistics Faculty Publications

In contrast to feature selection and gene set analysis, bi-level selection is a process of selecting not only important gene sets but also important genes within those gene sets. Depending on the order of selections, a bi-level selection method can be classified into three categories – forward selection, which first selects relevant gene sets followed by the selection of relevant individual genes; backward selection which takes the reversed order; and simultaneous selection, which performs the two tasks simultaneously usually with the aids of a penalized regression model. To test the existence of subtype-specific prognostic genes for non-small cell lung cancer …

Level Of Patient-Physician Agreement In Assessment Of Change Following Conservative Rehabilitation For Shoulder Pain, Stephanie D. Moore-Reed, W. Ben Kibler, Heather M. Bush, Timothy L. Uhl

Biostatistics Faculty Publications

Background Assessment of health-related status has been shown to vary between patients and physicians, although the degree of patient–physician discordance in the assessment of the change in status is unknown.

Methods Ninety-nine patients with shoulder dysfunction underwent a standardized physician examination and completed several self-reported questionnaires. All patients were prescribed the same physical therapy intervention. Six weeks later, the patients returned to the physician, when self-report questionnaires were re-assessed and the Global Rating of Change (GROC) was completed by the patient. The physician completed the GROC retrospectively. To determine agreement between patient and physician, intra-class correlation (ICC) coefficient and Pearson’s …

Using The Roc Curve To Measure Association And Evaluate Prediction Accuracy For A Binary Outcome, Jingjing Yin, Robert L. Vogel

Biostatistics Faculty Publications

This review article addresses the ROC curve and its advantage over the odds ratio to measure the association between a continuous variable and a binary outcome. A simple parametric model under the normality assumption and the method of Box-Cox transformation for non-normal data are discussed. Applications of the binormal model and the Box-Cox transformation under both univariate and multivariate inference are illustrated by a comprehensive data analysis tutorial. Finally, a summary and recommendations are given as to the usage of the binormal ROC curve.

Using Ranked Auxiliary Covariate As A More Efficient Sampling Design For Ancova Model: Analysis Of A Psychological Intervention To Buttress Resilience, Rajai Jabrah, Hani Samawi, Robert Vogel, Haresh Rochani, Daniel Linder

Biostatistics Faculty Publications

Drawing a sample can be costly or time consuming in some studies. However, it may be possible to rank the sampling units according to some baseline auxiliary covariates, which are easily obtainable, and/or cost efficient. Ranked set sampling (RSS) is a method to achieve this goal. In this paper, we propose a modified approach of the RSS method to allocate units into an experimental study that compares L groups. Computer simulation estimates the empirical nominal values and the empirical power values for the test procedure of comparing L different groups using modified RSS based on the regression approach in analysis …