Biostatistics Commons^™

Healthcare Utilization Costs Of Emerging Adults With Mood And Anxiety Disorders In An Early Intervention Treatment Program Compared To A Matched Cohort, Ava A. John-Baptiste, Lihua Li, Wanrudee Isaranuwatchai, Elizabeth Osuch, Kelly K. Anderson

Epidemiology and Biostatistics Publications

AIM: The First Episode Mood and Anxiety Disorder Program (FEMAP) provides treatment to emerging adults with mood and anxiety disorders in an accessible, youth-friendly environment. We sought to investigate FEMAP's impact on the costs of care.

METHODS: We conducted a retrospective observational study of one-year health service costs using linked administrative datasets to compare emerging adults treated at FEMAP (FEMAP users) to propensity-score matched controls (non-users). Costs from the perspective of the Ontario Ministry of Health and Long-Term Care, included drug benefit claims, inpatient, physician and ambulatory care services. We used bootstrapping to perform unadjusted comparisons between FEMAP users and …

Post-Acquisition Processing Confounds In Brain Volumetric Quantification Of White Matter Hyperintensities, Ahmed A. Bahrani, Omar M. Al-Janabi, Erin L. Abner, Shoshana H. Bardach, Richard J. Kryscio, Donna M. Wilcock, Charles D. Smith, Gregory A. Jicha

Neurology Faculty Publications

BACKGROUND: Disparate research sites using identical or near-identical magnetic resonance imaging (MRI) acquisition techniques often produce results that demonstrate significant variability regarding volumetric quantification of white matter hyperintensities (WMH) in the aging population. The sources of such variability have not previously been fully explored.

NEW METHOD: 3D FLAIR sequences from a group of randomly selected aged subjects were analyzed to identify sources-of-variability in post-acquisition processing that can be problematic when comparing WMH volumetric data across disparate sites. The methods developed focused on standardizing post-acquisition protocol processing methods to develop a protocol with less than 0.5% inter-rater variance.

RESULTS: A series …

Enhancing Timeliness Of Drug Overdose Mortality Surveillance: A Machine Learning Approach, Patrick J. Ward, Peter J. Rock, Svetla Slavova, April M. Young, Terry L. Bunn, Ramakanth Kavuluru

Kentucky Injury Prevention and Research Center Faculty Publications

BACKGROUND: Timely data is key to effective public health responses to epidemics. Drug overdose deaths are identified in surveillance systems through ICD-10 codes present on death certificates. ICD-10 coding takes time, but free-text information is available on death certificates prior to ICD-10 coding. The objective of this study was to develop a machine learning method to classify free-text death certificates as drug overdoses to provide faster drug overdose mortality surveillance.

METHODS: Using 2017–2018 Kentucky death certificate data, free-text fields were tokenized and features were created from these tokens using natural language processing (NLP). Word, bigram, and trigram features were created …

Differences In Duration Of Untreated Psychosis For Racial And Ethnic Minority Groups With First-Episode Psychosis: An Updated Systematic Review And Meta-Analysis., Nicole Schoer, Chen Wei Huang, Kelly K. Anderson

Epidemiology and Biostatistics Publications

PURPOSE: Ethnic minority groups with early psychosis may have longer treatment delays, potentially leading to poorer outcomes. We updated a previous systematic review of the literature on racial and ethnic differences in duration of untreated psychosis (DUP) among people with first-episode psychosis.

RESULTS: Six of 17 studies described significant differences across aggregated racial groups; however, the pooled estimates did not show differences across groups. Additional data from this update allowed for disaggregated analyses, finding that Black-African groups have a shorter DUP, whereas Black-Caribbean groups have longer DUP, relative to White groups.

CONCLUSIONS: These findings highlight the importance of in-depth research …

Socioemotional Selectivity And Psychological Health In Amyotrophic Lateral Sclerosis Patients And Caregivers: A Longitudinal, Dyadic Analysis, Suzanne C. Segerstrom, Edward J. Kasarskis, David W. Fardo, Philip M. Westgate

Psychology Faculty Publications

Objective: Socioemotional selectivity theory predicts that as the end of life approaches, goals and resources that provide immediate, hedonic reward become more important than those that provide delayed rewards. This study tested whether these goal domains differentially affected psychological health in the context of marital dyads in which one partner had been diagnosed with amyotrophic lateral sclerosis (ALS), a life-limiting disease.

Design: ALS patients (N = 102) being treated in three multidisciplinary clinics and their spouses (N = 100) reported their loneliness, financial worry and psychological health every 3 months for up to 18 months.

Main …

Effectiveness Of High-Intensity Interval Training For Fitness And Mobility Post Stroke: A Systematic Review., Joshua C. Wiener, Amanda Mcintyre, Scott Janssen, Jeffrey Ty Chow, Cristina Batey, Robert Teasell

Epidemiology and Biostatistics Publications

OBJECTIVE: To evaluate the evidence on the effectiveness of high-intensity interval training (HIIT) in improving fitness and mobility post stroke. TYPE: Systematic review.

LITERATURE SURVEY: Medline, Embase, CINAHL, PsycINFO, and Scopus were searched for articles published in English up to January 2018.

METHODOLOGY: Studies were included if the sample was adult human participants with stroke, the sample size was ≥3, and participants received >1 session of HIIT. Study and participant characteristics, treatment protocols, and results were extracted.

SYNTHESIS: Six studies with a total of 140 participants met inclusion criteria: three randomized controlled trials and three pre-post studies. HIIT protocols ranged …

Involuntary Hospitalization Among Young People With Early Psychosis: A Population-Based Study Using Health Administrative Data., Rebecca Rodrigues, Arlene G Macdougall, Guangyong Zou, Michael Lebenbaum, Paul Kurdyak, Lihua Li, Salimah Z Shariff, Kelly K Anderson

Epidemiology and Biostatistics Publications

OBJECTIVE: Early psychosis is an important window for establishing long-term trajectories. Involuntary hospitalization during this period may impact subsequent service engagement in people with newly diagnosed psychotic disorder. However, population-based studies of involuntary hospitalization in early psychosis are lacking. We sought to estimate the proportion of people aged 16 to 35 years with early psychosis in Ontario who are hospitalized involuntarily at first admission, and to identify the associated risk factors and outcomes.

METHODS: Using linked population-based health administrative data, we identified incident cases of non-affective psychosis over a five-year period (2009-2013) and followed cases for two years to ascertain …

Tumor Heterogeneity As A Predictor Of Response To Neoadjuvant Chemotherapy In Locally Advanced Rectal Cancer, Alissa Greenbaum, David R. Martin, Therese J. Bocklage, Ji-Hyun Lee, Scott A. Ness, Ashwani Rajput

Pathology and Laboratory Medicine Faculty Publications

BACKGROUND: Neoadjuvant chemoradiotherapy (nCRT) is the standard of care for locally advanced adenocarcinoma of the rectum, but it is currently unknown which patients have disease that will respond. This study tested the correlation between response to nCRT and intratumoral heterogeneity using next-generation sequencing assays.

PATIENTS AND METHODS: DNA was extracted from formalin-fixed, paraffin-embedded biopsy samples from a cohort of patients with locally advanced rectal adenocarcinoma (T3/4 or N1/2 disease) who received nCRT. High read-depth sequencing of > 400 cancer-relevant genes was performed. Tumor mutations and variant allele frequencies were used to calculate mutant-allele tumor heterogeneity (MATH) scores as measures of intratumoral …

Tdp-43 Proteinopathy In Aging: Associations With Risk-Associated Gene Variants And With Brain Parenchymal Thyroid Hormone Levels, Peter T. Nelson, Zsombor Gal, Wang-Xia Wang, Dana M. Niedowicz, Sergey C. Artiushin, Samuel Wycoff, Angela Wei, Gregory A. Jicha, David W. Fardo

Pathology and Laboratory Medicine Faculty Publications

TDP-43 proteinopathy is very prevalent among the elderly (affecting at least 25% of individuals over 85 years of age) and is associated with substantial cognitive impairment. Risk factors implicated in age-related TDP-43 proteinopathy include commonly inherited gene variants, comorbid Alzheimer's disease pathology, and thyroid hormone dysfunction. To test parameters that are associated with aging-related TDP-43 pathology, we performed exploratory analyses of pathologic, genetic, and biochemical data derived from research volunteers in the University of Kentucky Alzheimer's Disease Center autopsy cohort (n = 136 subjects). Digital pathologic methods were used to discriminate and quantify both neuritic and intracytoplasmic TDP-43 pathology …

Incorporating Pathway Information Into Feature Selection Towards Better Performed Gene Signatures, Suyan Tian, Chi Wang, Bing Wang

Biostatistics Faculty Publications

To analyze gene expression data with sophisticated grouping structures and to extract hidden patterns from such data, feature selection is of critical importance. It is well known that genes do not function in isolation but rather work together within various metabolic, regulatory, and signaling pathways. If the biological knowledge contained within these pathways is taken into account, the resulting method is a pathway-based algorithm. Studies have demonstrated that a pathway-based method usually outperforms its gene-based counterpart in which no biological knowledge is considered. In this article, a pathway-based feature selection is firstly divided into three major categories, namely, pathway-level selection, …

Saturated Fat Intake Is Associated With Lung Function In Individuals With Airflow Obstruction: Results From Nhanes 2007⁻2012, Kasey Cornell, Morshed Alam, Elizabeth Lyden, Lisa Wood, Tricia D. Levan, Tara M. Nordgren, Kristina L. Bailey, Corrine K. Hanson

Journal Articles: Biostatistics

Nutritional status is a well-recognized prognostic indicator in chronic obstructive pulmonary disease (COPD); however, very little is known about the relationship between lung function and saturated fat intake. We used data from the cross-sectional National Health and Nutrition Examination Surveys (NHANES) to assess the relationship between saturated fatty acid (SFA) intake and lung function in the general US adult population. Adults in NHANES (2007⁻2012) with pre-bronchodilator spirometry measurements and dietary SFA intake were included. Primary outcomes were lung function including forced expiratory volume in one second (FEV₁)

Large-Scale Genome-Wide Meta-Analysis Of Polycystic Ovary Syndrome Suggests Shared Genetic Architecture For Different Diagnosis Criteria, Felix Day, Tugce Karaderi, Michelle R. Jones, Cindy Meun, Chunyan He, Alex Drong, Peter Kraft, Nan Lin, Hongyan Huang, Linda Broer, Reedik Magi, Richa Saxena, Triin Laisk, Margrit Urbanek, M. Geoffrey Hayes, Gudmar Thorleifsson, Juan Fernandez-Tajes, Anubha Mahajan, Benjamin H. Mullin, Bronwyn G. A. Stuckey, Timothy D. Spector, Scott G. Wilson, Mark O. Goodarzi, Lea Davis, Barbara Obermayer-Pietsch, André G. Uitterlinden, Verneri Anttila, Benjamin M. Neale, Marjo-Riitta Jarvelin, Bart Fauser

Internal Medicine Faculty Publications

Polycystic ovary syndrome (PCOS) is a disorder characterized by hyperandrogenism, ovulatory dysfunction and polycystic ovarian morphology. Affected women frequently have metabolic disturbances including insulin resistance and dysregulation of glucose homeostasis. PCOS is diagnosed with two different sets of diagnostic criteria, resulting in a phenotypic spectrum of PCOS cases. The genetic similarities between cases diagnosed based on the two criteria have been largely unknown. Previous studies in Chinese and European subjects have identified 16 loci associated with risk of PCOS. We report a fixed-effect, inverse-weighted-variance meta-analysis from 10,074 PCOS cases and 103,164 controls of European ancestry and characterisation of PCOS related …

Serum Nutrient Levels And Aging Effects On Periodontitis, Jeffrey L Ebersole, Joshua Lambert, Heather Bush, Pinar Emecen Huja, Arpita Basu

Biostatistics Faculty Publications

Periodontal disease damages tissues as a result of dysregulated host responses against the chronic bacterial biofilm insult and approximately 50% of US adults > 30 years old exhibit periodontitis. The association of five blood nutrients and periodontitis were evaluated due to our previous findings regarding a potential protective effect for these nutrients in periodontal disease derived from the US population sampled as part of the National Health and Nutrition Examination Survey (1999–2004). Data from over 15,000 subjects was analyzed for blood levels of cis-β-carotene, β-cryptoxanthin, folate, vitamin D, and vitamin E, linked with analysis of the presence and severity of periodontitis. …

Subject Level Clustering Using A Negative Binomial Model For Small Transcriptomic Studies., Qian Li, Janelle R. Noel-Macdonnell, Devin C. Koestler, Ellen L. Goode, Brooke L. Fridley

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Unsupervised clustering represents one of the most widely applied methods in analysis of high-throughput 'omics data. A variety of unsupervised model-based or parametric clustering methods and non-parametric clustering methods have been proposed for RNA-seq count data, most of which perform well for large samples, e.g. N ≥ 500. A common issue when analyzing limited samples of RNA-seq count data is that the data follows an over-dispersed distribution, and thus a Negative Binomial likelihood model is often used. Thus, we have developed a Negative Binomial model-based (NBMB) clustering approach for application to RNA-seq studies.

RESULTS: We have developed a Negative …

Safety, Tolerability, And Pharmacokinetics Of Long-Acting Injectable Cabotegravir In Low-Risk Hiv-Uninfected Individuals: Hptn 077, A Phase 2a Randomized Controlled Trial., Raphael J Landovitz, Sue Li, Beatriz Grinsztejn, Halima Dawood, Albert Y Liu, Manya Magnus, Mina C Hosseinipour, Ravindre Panchia, Leslie Cottle, Gordon Chau, Paul Richardson, Mark A Marzinke, Craig W Hendrix, Susan H Eshleman, Yinfeng Zhang, Elizabeth Tolley, Jeremy Sugarman, Ryan Kofron, Adeola Adeyeye, David Burns, Alex R Rinehart, David Margolis, William R Spreen, Myron S Cohen, Marybeth Mccauley, Joseph J Eron

Epidemiology Faculty Publications

BACKGROUND: Cabotegravir (CAB) is a novel strand-transfer integrase inhibitor being developed for HIV treatment and prevention. CAB is formulated both as an immediate-release oral tablet for daily administration and as a long-acting injectable suspension (long-acting CAB [CAB LA]) for intramuscular (IM) administration, which delivers prolonged plasma exposure to the drug after IM injection. HIV Prevention Trials Network study 077 (HPTN 077) evaluated the safety, tolerability, and pharmacokinetics of CAB LA in HIV-uninfected males and females at 8 sites in Brazil, Malawi, South Africa, and the United States.

METHODS AND FINDINGS: HPTN 077 was a double-blind, placebo-controlled phase 2a trial. Healthy …

Trends In Obesity And Multimorbidity In Canada., Michael Lebenbaum, Gregory S Zaric, Amardeep Thind, Sisira Sarma

Epidemiology and Biostatistics Publications

Very few studies have examined trends in multimorbidity over time and even fewer have examined trends over time across different body mass index (BMI) groups. Given a general decline in death rates but increased cardiovascular risk factors among individuals with obesity, the trend in the association between obesity and multimorbidity is hypothesized to be increasing over time. The data for our study came from the 1996-97 National Population Health Survey and the 2005 and 2012-13 Canadian Community Health Surveys (N = 277,366 across all 3 surveys). We examined trends in the association between BMI groups and multimorbidity using a logistic …

Blood Transfusions In Preterm Infants: Changes On Perfusion Index And Intermittent Hypoxemia, Katrina T. Ibonia, Henrietta S. Bada, Philip M. Westgate, Enrique Gomez Pomar, Prasad Bhandary, Abhijit R. Patwardhan, Elie G. Abu Jawdeh

Pediatrics Faculty Publications

BACKGROUND

Red blood cell (RBC) transfusion decreases intermittent hypoxemia (IH) events beyond the first week of life. This benefit may be related to improved perfusion to the respiratory control network. Perfusion index (PI) is a perfusion measure provided by the pulse oximeter. We hypothesized that the benefit in IH after RBC transfusion is associated with an increase in PI. In addition, we assessed the value of PI and clinical measures in predicting the effect of RBC transfusion on IH.

STUDY DESIGN AND METHODS

We prospectively enrolled infants less than 30 weeks' gestation age. PI and oxygen saturation (SpO₂) …

Family Physician Remuneration Schemes And Specialist Referrals: Quasi-Experimental Evidence From Ontario, Canada., Sisira Sarma, Nirav Mehta, Rose Anne Devlin, Koffi Ahoto Kpelitse, Lihua Li

Epidemiology and Biostatistics Publications

Understanding how family physicians respond to incentives from remuneration schemes is a central theme in the literature. One understudied aspect is referrals to specialists. Although the theoretical literature has suggested that capitation increases referrals to specialists, the empirical evidence is mixed. We push forward the empirical research on this question by studying family physicians who switched from blended fee-for-service to blended capitation in Ontario, Canada. Using several health administrative databases from 2005 to 2013, we rely on inverse probability weighting with fixed-effects regression models to account for observed and unobserved differences between the switchers and nonswitchers. Switching from blended fee-for-service …

Neurotensin Receptor 3/Sortilin Contributes To Tumorigenesis Of Neuroendocrine Tumors Through Augmentation Of Cell Adhesion And Migration, Ji Tae Kim, Dana L. Napier, Heidi L. Weiss, Eun Y. Lee, Courtney M. Townsend, B. Mark Evers

Markey Cancer Center Faculty Publications

Neurotensin (NTS), a 13–amino acid peptide which is distributed predominantly along gastrointestinal tract, has multiple physiologic and pathologic functions, and its effects are mediated by three distinct NTS receptors (NTSRs). Overexpression and activation of NTS signaling components, especially NTS and/or NTSR1, are closely linked with cancer progression and metastasis in various types of cancers including neuroendocrine tumors (NETs). Although deregulation of NTSR3/sortilin has been implicated in a variety of human diseases, the expression and role of NTSR3/sortilin in NETs have not been elucidated. In this study, we investigated the expression and oncogenic effect of NTSR3/sortilin in NETs. Increased protein levels …

A Customized Quantitative Pcr Microrna Panel Provides A Technically Robust Context For Studying Neurodegenerative Disease Biomarkers And Indicates A High Correlation Between Cerebrospinal Fluid And Choroid Plexus Microrna Expression, Wang-Xia Wang, David W. Fardo, Gregory A. Jicha, Peter T. Nelson

Sanders-Brown Center on Aging Faculty Publications

MicroRNA (miRNA) expression varies in association with different tissue types and in diseases. Having been found in body fluids including blood and cerebrospinal fluid (CSF), miRNAs constitute potential biomarkers. CSF miRNAs have been proposed as biomarkers for neurodegenerative diseases; however, there is a lack of consensus about the best candidate miRNA biomarkers and there has been variability in results from different research centers, perhaps due to technical factors. Here, we sought to optimize technical parameters for CSF miRNA studies. We examined different RNA isolation methods and performed miRNA expression profiling with TaqMan® miRNA Arrays. More specifically, we developed a customized …

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 …

Increased Birth Weight Is Associated With Altered Gene Expression In Neonatal Foreskin, Leryn J. Reynolds, Rebecca I. Pollack, Richard J. Charnigo, Cetewayo S. Rashid, Arnold J. Stromberg, Shu Shen, John O'Brien, Kevin J. Pearson

Pharmacology and Nutritional Sciences Faculty Publications

Elevated birth weight is linked to glucose intolerance and obesity health-related complications later in life. No studies have examined if infant birth weight is associated with gene expression markers of obesity and inflammation in a tissue that comes directly from the infant following birth. We evaluated the association between birth weight and gene expression on fetal programming of obesity. Foreskin samples were collected following circumcision, and gene expression analyzed comparing the 15% greatest birth weight infants (n = 7) v. the remainder of the cohort (n = 40). Multivariate linear regression models were fit to relate expression levels on differentially …

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 …

Risk Of Incident Clinical Diagnosis Of Alzheimer's Disease-Type Dementia Attributable To Pathology-Confirmed Vascular Disease, Hiroko H. Dodge, Jian Zhu, Randy Woltjer, Peter T. Nelson, David A. Bennett, Nigel J. Cairns, David W. Fardo, Jeffrey A. Kaye, Deniz-Erten Lyons, Nora Mattek, Julie A. Schneider, Lisa C. Silbert, Chengjie Xiong, Lei Yu, Frederick A. Schmitt, Richard J. Kryscio, Erin L. Abner, Smart Data Consortium

Sanders-Brown Center on Aging Faculty Publications

INTRODUCTION: The presence of cerebrovascular pathology may increase the risk of clinical diagnosis of Alzheimer's disease (AD).

METHODS: We examined excess risk of incident clinical diagnosis of AD (probable and possible AD) posed by the presence of lacunes and large infarcts beyond AD pathology using data from the Statistical Modeling of Aging and Risk of Transition study, a consortium of longitudinal cohort studies with more than 2000 autopsies. We created six mutually exclusive pathology patterns combining three levels of AD pathology (low, moderate, or high AD pathology) and two levels of vascular pathology (without lacunes and large infarcts or with …

Demographics, Patterns Of Care, And Survival In Pediatric Medulloblastoma, Emily V. Dressler, Therese A. Dolecek, Meng Liu, John L. Villano

Internal Medicine Faculty Publications

We evaluated the American College of Surgeon’s National Cancer Data Base (NCDB) to describe current hospital-based epidemiologic frequency, survival, and patterns of care of pediatric medulloblastoma. We analyzed NCDB 1998–2011 data on medulloblastoma for children ages 0–19 years using logistic and poisson regression, Kaplan–Meier survival estimates, and Cox proportional hazards models. 3647 cases of medulloblastoma in those aged 0–19 years were identified. Chemotherapy was received by 79 and 74% received radiation, with 65% receiving both therapies. Those who received radiation were more likely to be older than four, while those who received chemotherapy were more likely to be age four …

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 …

Functional Human Grin2b Promoter Polymorphism And Variation Of Mental Processing Speed In Older Adults, Yang Jiang, Ming Kuan Lin, Gregory A. Jicha, Xiuhua Ding, Sabrina L. Mcilwrath, David W. Fardo, Lucas S. Broster, Frederick A. Schmitt, Richard J. Kryscio, Robert H. Lipsky

Behavioral Science Faculty Publications

We investigated the role of a single nucleotide polymorphism rs3764030 (G > A) within the human GRIN2B promoter in mental processing speed in healthy, cognitively intact, older adults. In vitro DNA-binding and reporter gene assays of different allele combinations in transfected cells showed that the A allele was a gain-of-function variant associated with increasing GRIN2B mRNA levels. We tested the hypothesis that individuals with A allele will have better memory performance (i.e. faster reaction times) in older age. Twenty-eight older adults (ages 65-86) from a well-characterized longitudinal cohort were recruited and performed a modified delayed match-to-sample task. The rs3764030 polymorphism was …

Outcomes After Diagnosis Of Mild Cognitive Impairment In A Large Autopsy Series, Erin L. Abner, Richard J. Kryscio, Frederick A. Schmitt, David W. Fardo, Daniela C. Moga, Eseosa T. Ighodaro, Gregory A. Jicha, Lei Yu, Hiroko H. Dodge, Chengjie Xiong, Randall L. Woltjer, Julie A. Schneider, Nigel J. Cairns, David A. Bennett, Peter T. Nelson

Epidemiology and Environmental Health Faculty Publications

OBJECTIVE: To determine clinical and neuropathological outcomes following a clinical diagnosis of mild cognitive impairment (MCI).

METHODS: Data were drawn from a large autopsy series (N = 1,337) of individuals followed longitudinally from normal or MCI status to death, derived from 4 Alzheimer Disease (AD) Centers in the United States.

RESULTS: Mean follow‐up was 7.9 years. Of the 874 individuals ever diagnosed with MCI, final clinical diagnoses were varied: 39.2% died with an MCI diagnosis, 46.8% with a dementia diagnosis, and 13.9% with a diagnosis of intact cognition. The latter group had pathological features resembling those with a final clinical …

A Statistical Method For The Conservative Adjustment Of False Discovery Rate (Q-Value)., Yinglei Lai

Epidemiology Faculty Publications

BACKGROUND: q-value is a widely used statistical method for estimating false discovery rate (FDR), which is a conventional significance measure in the analysis of genome-wide expression data. q-value is a random variable and it may underestimate FDR in practice. An underestimated FDR can lead to unexpected false discoveries in the follow-up validation experiments. This issue has not been well addressed in literature, especially in the situation when the permutation procedure is necessary for p-value calculation.

RESULTS: We proposed a statistical method for the conservative adjustment of q-value. In practice, it is usually necessary to calculate p-value by a permutation procedure. …