Physical Sciences and Mathematics Commons^™

Analysis Of Genes (Tmem106b, Grn, Abcc9, Kcnmb2, And Apoe) Implicated In Risk For Late-Nc And Hippocampal Sclerosis Provides Pathogenetic Insights: A Retrospective Genetic Association Study, Adam J. Dugan, Peter T. Nelson, Yuriko Katsumata, Lincoln M. P. Shade, Kevin L. Boehme, Merilee A. Teylan, Matthew D. Cykowski, Shubhabrata Mukherjee, John S. K. Kauwe, Timothy J. Hohman, Julie A. Schneider, Alzheimer’S Disease Genetics Consortium, David W. Fardo

Biostatistics Faculty Publications

Limbic-predominant age-related TDP-43 encephalopathy neuropathologic change (LATE-NC) is the most prevalent subtype of TDP-43 proteinopathy, affecting up to 1/3rd of aged persons. LATE-NC often co-occurs with hippocampal sclerosis (HS) pathology. It is currently unknown why some individuals with LATE-NC develop HS while others do not, but genetics may play a role. Previous studies found associations between LATE-NC phenotypes and specific genes: TMEM106B, GRN, ABCC9, KCNMB2, and APOE. Data from research participants with genomic and autopsy measures from the National Alzheimer’s Coordinating Center (NACC; n = 631 subjects included) and the Religious Orders Study and Memory …

Associations Of Circulating Dimethylarginines With The Metabolic Syndrome In The Framingham Offspring Study, Ibrahim Musa Yola, Carlee Moser, Meredith S. Duncan, Edzard Schwedhelm, Dorothee Atzler, Renke Maas, Juliane Hannemann, Rainer H. Böger, Ramachandran S. Vasan, Vanessa Xanthakis

Biostatistics Faculty Publications

BACKGROUND: Circulating levels of the endogenous inhibitor of nitric oxide synthase, asymmetric dimethylarginine (ADMA), are positively associated with the prevalence of metabolic syndrome (MetS) in cross-sectional investigations. It is unclear if circulating ADMA and other methylarginines are associated with incident MetS prospectively.

METHODS: We related circulating ADMA, symmetric dimethylarginine (SDMA), L-arginine (ARG) concentrations (measured with a validated tandem mass spectrometry assay) and the ARG/ADMA ratio to MetS and its components in 2914 (cross-sectional analysis, logistic regression; mean age 58 years, 55% women) and 1656 (prospective analysis, Cox regression; mean age 56 years, 59% women) individuals from the Framingham Offspring Study …

Age And Sex Are Associated With The Plasma Lipidome: Findings From The Goldn Study, Emily Slade, Marguerite R. Irvin, Kevin Xie, Donna K. Arnett, Steven A. Claas, Tobias Kind, David W. Fardo, Gregory A. Graf

Biostatistics Faculty Publications

Background
Developing an understanding of the biochemistry of aging in both sexes is critical for managing disease throughout the lifespan. Lipidomic associations with age and sex have been reported, but prior studies are limited by measurements in serum rather than plasma or by participants taking lipid-lowering medications.

Methods
Our study included lipidomic data from 980 participants aged 18–87 years old from the Genetics of Lipid-Lowering Drugs and Diet Network (GOLDN). Participants were off lipid-lowering medications for at least 4 weeks, and signal intensities of 413 known lipid species were measured in plasma. We examined linear age and sex associations with …

Measurement Matters: Changing Penalty Calculations Under The Hospital Acquired Condition Reduction Program (Hacrp) Cost Hospitals Millions, Olga A. Vsevolozhskaya, Karina C. Manz, Pierre M. Zephyr, Teresa M. Waters

Biostatistics Faculty Publications

BACKGROUND: Since October 2014, the Centers for Medicare and Medicaid Services has penalized 25% of U.S. hospitals with the highest rates of hospital-acquired conditions under the Hospital Acquired Conditions Reduction Program (HACRP). While early evaluations of the HACRP program reported cumulative reductions in hospital-acquired conditions, more recent studies have not found a clear association between receipt of the HACRP penalty and hospital quality of care. We posit that some of this disconnect may be driven by frequent scoring updates. The sensitivity of the HACRP penalties to updates in the program's scoring methodology has not been independently evaluated.

METHODS: We used …

Distinct Clinicopathologic Clusters Of Persons With Tdp-43 Proteinopathy, Yuriko Katsumata, Erin L. Abner, Shama Karanth, Merilee A. Teylan, Charles N. Mock, Matthew D. Cykowski, Edward B. Lee, Kevin L. Boehme, Shubhabrata Mukherjee, John S. K. Kauwe, Richard J. Kryscio, Frederick A. Schmitt, David W. Fardo, Peter T. Nelson

Biostatistics Faculty Publications

To better understand clinical and neuropathological features of TDP-43 proteinopathies, data were analyzed from autopsied research volunteers who were followed in the National Alzheimer’s Coordinating Center (NACC) data set. All subjects (n = 495) had autopsy-proven TDP-43 proteinopathy as an inclusion criterion. Subjects underwent comprehensive longitudinal clinical evaluations yearly for 6.9 years before death on average. We tested whether an unsupervised clustering algorithm could detect coherent groups of TDP-43 immunopositive cases based on age at death and extensive neuropathologic data. Although many of the brains had mixed pathologies, four discernible clusters were identified. Key differentiating features were age at …

Epidemiologic Evaluation Of Nhanes For Environmental Factors And Periodontal Disease, P. Emecen-Huja, H. -F. Li, J. L. Ebersole, J. Lambert, Heather M. Bush

Biostatistics Faculty Publications

Periodontitis is a chronic inflammation that destroys periodontal tissues caused by the accumulation of bacterial biofilms that can be affected by environmental factors. This report describes an association study to evaluate the relationship of environmental factors to the expression of periodontitis using the National Health and Nutrition Examination Study (NHANES) from 1999–2004. A wide range of environmental variables (156) were assessed in patients categorized for periodontitis (n = 8884). Multiple statistical approaches were used to explore this dataset and identify environmental variable patterns that enhanced or lowered the prevalence of periodontitis. Our findings indicate an array of environmental variables were …

Interrupted Time Series Design To Evaluate The Effect Of The Icd-9-Cm To Icd-10-Cm Coding Transition On Injury Hospitalization Trends, Svetla Slavova, Julia F. Costich, Huong Luu, Judith Fields, Barbara A. Gabella, Sergey Tarima, Terry L. Bunn

Biostatistics Faculty Publications

Background: Implementation of the International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) in the U.S. on October 1, 2015 was a significant policy change with the potential to affect established injury morbidity trends. This study used data from a single state to demonstrate 1) the use of a statistical method to estimate the effect of this coding transition on injury hospitalization trends, and 2) interpretation of significant changes in injury trends in the context of the structural and conceptual differences between ICD-9-CM and ICD-10-CM, the new ICD-10-CM-specific coding guidelines, and proposed ICD-10-CM-based framework for reporting of injuries by intent …

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 …

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 …

Evaluating The Efficiency Of Treatment Comparison In Crossover Design By Allocating Subjects Based On Ranked Auxiliary Variable, Yisong Huang, Hani Samawi, Robert Vogel, Jingjing Yin, Worlanyo E. Gato, Daniel Linder

Biostatistics Faculty Publications

The validity of statistical inference depends on proper randomization methods. However, even with proper randomization, we can have imbalanced with respect to important characteristics. In this paper, we introduce a method based on ranked auxiliary variables for treatment allocation in crossover designs using Latin squares models. We evaluate the improvement of the efficiency in treatment comparisons using the proposed method. Our simulation study reveals that our proposed method provides a more powerful test compared to simple randomization with the same sample size. The proposed method is illustrated by conducting an experiment to compare two different concentrations of titanium dioxide nanofiber …

Estimation Of P(X > Y) When X And Y Are Dependent Random Variables Using Different Bivariate Sampling Schemes, Hani M. Samawi, Amal Helu, Haresh Rochani, Jingjing Yin, Daniel Linder

Biostatistics Faculty Publications

The stress-strength models have been intensively investigated in the literature in regards of estimating the reliability θ = P (X > Y) using parametric and nonparametric approaches under different sampling schemes when X and Y are independent random variables. In this paper, we consider the problem of estimating θ when (X, Y) are dependent random variables with a bivariate underlying distribution. The empirical and kernel estimates of θ = P (X > Y), based on bivariate ranked set sampling (BVRSS) are considered, when (X, Y) are paired dependent continuous random variables. The estimators obtained are compared to their counterpart, bivariate simple random …

Improved Estimation Of Optimal Cut-Off Point Associated With Youden Index Using Ranked Set Sampling, Jingjing Yin, Hani M. Samawi, Daniel Linder

Biostatistics Faculty Publications

A diagnostic cut-off point of a biomarker measurement is needed for classifying a random subject to be either diseased or healthy. However, the cut-off point is usually unknown and needs to be estimated by some optimization criteria. One important criterion is the Youden index, which has been widely adopted in practice. The Youden index, which is defined as the maximum of (sensitivity + specificity −1), directly measures the largest total diagnostic accuracy a biomarker can achieve. Therefore, it is desirable to estimate the optimal cut-off point associated with the Youden index. Sometimes, taking the actual measurements of a biomarker is …

Uncovering Local Trends In Genetic Effects Of Multiple Phenotypes Via Functional Linear Models, Olga A. Vsevolozhskaya, Dmitri V. Zaykin, David A. Barondess, Xiaoren Tong, Sneha Jadhav, Qing Lu

Biostatistics Faculty Publications

Recent technological advances equipped researchers with capabilities that go beyond traditional genotyping of loci known to be polymorphic in a general population. Genetic sequences of study participants can now be assessed directly. This capability removed technology-driven bias toward scoring predominantly common polymorphisms and let researchers reveal a wealth of rare and sample-specific variants. Although the relative contributions of rare and common polymorphisms to trait variation are being debated, researchers are faced with the need for new statistical tools for simultaneous evaluation of all variants within a region. Several research groups demonstrated flexibility and good statistical power of the functional linear …

Motorcycle Helmet Effectiveness In Reducing Head, Face And Brain Injuries By State And Helmet Law, Cody S. Olsen, Andrea M. Thomas, Michael Singleton, Anna M. Gaichas, Tracy J. Smith, Gary A. Smith, Justin Peng, Michael J. Bauer, Ming Qu, Denise Yeager, Timothy Kerns, Cynthia Burch, Lawrence J. Cook

Biostatistics Faculty Publications

Background: Despite evidence that motorcycle helmets reduce morbidity and mortality, helmet laws and rates of helmet use vary by state in the U.S.

Methods: We pooled data from eleven states: five with universal laws requiring all motorcyclists to wear a helmet, and six with partial laws requiring only a subset of motorcyclists to wear a helmet. Data were combined in the Crash Outcome Data Evaluation System's General Use Model and included motorcycle crash records probabilistically linked to emergency department and inpatient discharges for years 2005-2008. Medical outcomes were compared between partial and universal helmet law settings. We estimated adjusted relative …

A Test Of Symmetry Based On The Kernel Kullback-Leibler Information With Application To Base Deficit Data, Hani M. Samawi, Robert L. Vogel

Biostatistics Faculty Publications

The assumption of the symmetry of the underlying distribution is important to many statistical inference and modeling procedures. This paper provides a test of symmetry using kernel density estimation and the Kullback-Leibler information. Based on simulation studies, the new test procedure outperforms other tests of symmetry found in the literature, including the Runs Test of Symmetry. We illustrate our new procedure using real data.

Correction Of Verication Bias Using Log-Linear Models For A Single Binaryscale Diagnostic Tests, Haresh Rochani, Hani M. Samawi, Robert L. Vogel, Jingjing Yin

Biostatistics Faculty Publications

In diagnostic medicine, the test that determines the true disease status without an error is referred to as the gold standard. Even when a gold standard exists, it is extremely difficult to verify each patient due to the issues of costeffectiveness and invasive nature of the procedures. In practice some of the patients with test results are not selected for verification of the disease status which results in verification bias for diagnostic tests. The ability of the diagnostic test to correctly identify the patients with and without the disease can be evaluated by measures such as sensitivity, specificity and predictive …

Monitoring For Adverse Events Post Marketing Approval Of Drugs, Karl E. Peace, Macaulay Okwuokenye

Biostatistics Faculty Publications

This brief communication provides information to those developing monitoring plans for serious adverse events (SAE’s) following regulatory approval of a new drug. In addition, we (1) illustrate how many patients would need to be treated in order to have high confidence of seeing at least 1 pre-specified SAE, (2) show that absence of proof of a SAE is not proof of absence of that SAE, and (3) identify statistical methodology that could be used for formal statistical monitoring of SAE’s.

Size And Power Of Tests Of Hypotheses On Survival Parameters From The Lindley Distribution With Covariates, Macaulay Okwuokenye, Karl E. Peace

Biostatistics Faculty Publications

The Lindley model is considered as an alternative model facilitating analyses of time-to-event data with covariates. Covariate information is incorporated using the Cox’s proportional hazard model with the Lindley model at the timedependent component. Simulation studies are performed to assess the size and power of tests of hypotheses on parameters arising from maximum likelihood estimators of parameters in the Lindley model. Results are contrasted with that arising from Cox’s partial maximum likelihood estimator. The Linley model is used to analyze a publicly available data set and contrasted with other models.

Joint Modeling Of Treatment Effect On Time-To-Event Endpoint And Safety Covariates In Control Clinical Trial Data Analysis, Kao-Tai Tsai, Karl E. Peace

Biostatistics Faculty Publications

It is a common practice to perform a separate analysis of efficacy and safety data from clinical trials to estimate the benefit and risk aspects of a particular treatment regimen. However, by doing so, one is likely to miss the complete picture of the treatment effect given that these data are generated from the same study subjects and therefore most likely will be correlated. Therefore, it is desirable to analyze these data jointly to obtain a more complete profile of the treatment regimen. A substantial number of statistical methodologies have been proposed in the last decade to model the time-to-event …

Inequalities And Approximations Of Weighted Distributions By Lindley Reliability Measures, And The Lindley-Cox Model With Applications, Broderick O. Oluyede, Macaulay Okwuokenye, Karl E. Peace

Biostatistics Faculty Publications

In this note, stochastic comparisons and results for weighted and Lindley models are presented. Approximation of weighted distributions via Lindley distribution in the class of increasing failure rate (IFR) and decreasing failure rate (DFR) weighted distributions with monotone weight functions are obtained including approximations via the length-biased Lindley distribution. Some useful bounds and moment-type inequality for weighted life distributions and applications are presented. Incorporation of covariates into Lindley model is considered and an application to illustrate the usefulness and applicability of the proposed Lindley-Cox model is given.

How Long Does That 10-Year Smoke Alarm Really Last? A Survival Analysis Of Smoke Alarms Installed Through The Saife Program In Rural Georgia, Haresh Rochani, Valamar Malika Reagon, Steve Davidson

Biostatistics Faculty Publications

Background: When functioning properly, a smoke alarm alerts individuals in the residence that smoke is near the alarm. Smoke alarms serve as a primary prevention mechanism to abate morbidity and mortality related to residential fires.

Methods: Using survival analysis, we examined the length of operability of 10-year lithium battery powered smoke alarms installed through the Georgia Public Health/CDC SAIFE program in Moultrie, Georgia. Attempts were made to reach all homes in the city limits. The premise of the study is that geographic clusters (in the case of Moultrie city quadrants) are associated with decreases in the length of time that …

A More Efficient Nonparametric Test Of Symmetry Based On Overlapping Coefficient, Hani M. Samawi, Robert L. Vogel

Biostatistics Faculty Publications

In this paper we provide a more efficient nonparametric test of symmetry based on the empirical overlap coefficient using kernel density estimation applied to an extreme order statistics, namely extreme ranked set sampling. Our simulation investigation reveals that our proposed test of symmetry is at least as powerful as currently available tests of symmetry. Intensive simulation is conducted to examine the power of the proposed test. An illustration is provided using cardiac output and body weight of neonates in a neonatal intensive care unit.

Overview Of Inference About Roc Curve In Medical Diagnosis, Jingjing Yin

Biostatistics Faculty Publications

Medical diagnosis aims to identify diseased individuals through the evaluation of the measurements of some biomarkers by performing a diagnostic test based on some biomarker measurements. Biomarkers are measured on either discrete or continuous scale and continuous biomarkers are utilized more often in medical practice. This article introduces the most popular tool for evaluating continuous biomarkers: the Receiver Operating Characteristic (ROC) curve.

Lung Flute Improves Symptoms And Health Status In Copd With Chronic Bronchitis: A 26 Week Randomized Controlled Trial, Sanjay Sethi, Jingjing Yin, Pamela K. Anderson

Biostatistics Faculty Publications

Background: Chronic obstructive pulmonary disease (COPD) is characterized by mucus hypersecretion that contributes to disease related morbidity and is associated with increased mortality. The Lung Flute® is a new respiratory device that produces a low frequency acoustic wave with moderately vigorous exhalation to increase mucus clearance. We hypothesized that the Lung Flute, used on a twice daily basis will provide clinical benefit to patients with COPD with chronic bronchitis.

Methods: We performed a 26 week randomized, non-intervention controlled, single center, open label trial in 69 patients with COPD and Chronic Bronchitis. The primary endpoint was change in respiratory symptoms measured …

A Novel Three Serum Phospholipid Panel Differentiates Normal Individuals From Those With Prostate Cancer, Nima Patel, Robert L. Vogel, Kumar Chandra-Kuntal, Wayne Glasgow, Uddhav Kelavkar

Biostatistics Faculty Publications

Background: The results of prostate specific antigen (PSA) and digital rectal examination (DRE) screenings lead to both under and over treatment of prostate cancer (PCa). As such, there is an urgent need for the identification and evaluation of new markers for early diagnosis and disease prognosis. Studies have shown a link between PCa, lipids and lipid metabolism. Therefore, the aim of this study was to examine the concentrations and distribution of serum lipids in patients with PCa as compared with serum from controls.

Method: Using Electrospray ionization mass spectrometry (ESI-MS/MS) lipid profiling, we analyzed serum phospholipids from age-matched subjects who …

A Phylogenetic Model For Understanding The Effect Of Gene Duplication On Cancer Progression, Qin Ma, Jaxk H. Reeves, David A. Liberles, Lili Yu, Zheng Chang, Jing Zhao, Juan Cui, Ying Xu, Liang Liu

Biostatistics Faculty Publications

As biotechnology advances rapidly, a tremendous amount of cancer genetic data has become available, providing an unprecedented opportunity for understanding the genetic mechanisms of cancer. To understand the effects of duplications and deletions on cancer progression, two genomes (normal and tumor) were sequenced from each of five stomach cancer patients in different stages (I, II, III and IV). We developed a phylogenetic model for analyzing stomach cancer data. The model assumes that duplication and deletion occur in accordance with a continuous time Markov Chain along the branches of a phylogenetic tree attached with five extended branches leading to the tumor …

Causality Is Logically Definable-Toward An Equilibrium-Based Computing Paradigm Of Quantum Agents And Quantum Intelligence (Qaqi), Wen-Ran Zhang, Karl E. Peace

Biostatistics Faculty Publications

A survey on agents, causality and intelligence is presented and an equilibrium-based computing paradigm of quantum agents and quantum intelligence (QAQI) is proposed. In the survey, Aristotle’s causality principle and its historical extensions by David Hume, Bertrand Russell, Lotfi Zadeh, Donald Rubin, Judea Pearl, Niels Bohr, Albert Einstein, David Bohm, and the causal set initiative are reviewed; bipolar dynamic logic (BDL) is introduced as a causal logic for bipolar inductive and deductive reasoning; bipolar quantum linear algebra (BQLA) is introduced as a causal algebra for quantum agent interaction and formation. Despite the widely held view that causality is undefinable with …

Revealing The Ubiquitous Effects Of Quantum Entanglement-Toward A Notion Of God Logic, Wen-Ran Zhang, Karl E. Peace

Biostatistics Faculty Publications

Following Spinoza-Einstein’s interpretation of God or nature, the notion “God Logic” is proposed. This notion is to serve as an elicitation for a consistent set of necessary criteria for: 1) developing the logical foundation of quantum gravity as envisaged by Einstein, 2) revealing the ubiquitous effects of quantum entanglement as suggested by Roger Penrose, and 3) programming the universe as proposed by Seth Lloyd. An evolving set of eleven criteria is proposed for the notion. The possibility of inventing such a logical system is analyzed. A supersymmetrical candidate logic of negative-positive energy dynamic equilibrium is introduced and assessed against the …

Analysis Of Subgroup Data Of Clinical Trials, Kao-Tai Tsai, Karl E. Peace

Biostatistics Faculty Publications

Large randomized controlled clinical trials are the gold standard to evaluate and compare the effects of treatments. It is common practice for investigators to explore and even attempt to compare treatments, beyond the first round of primary analyses, for various subsets of the study populations based on scientific or clinical interests to take advantage of the potentially rich information contained in the clinical database. Although subjects are randomized to treatment groups in clinical trials, this does not imply the same degree of randomization among sub-populations of the original trials. Therefore, comparisons of treatments in sub-populations may not produce fair and …