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The Efficacy Of Plant-Based Dietary Program In Patients With Diabetes: A Pilot Study, Reuben Adatorwovor, Nisha Sharma, Dakota Mccoy, Sharon Wasserstrom, Matthew Robinson, Jacquelyn Nyenhuis, Sowmya Suryanarayanan Dec 2021

The Efficacy Of Plant-Based Dietary Program In Patients With Diabetes: A Pilot Study, Reuben Adatorwovor, Nisha Sharma, Dakota Mccoy, Sharon Wasserstrom, Matthew Robinson, Jacquelyn Nyenhuis, Sowmya Suryanarayanan

Biostatistics Faculty Publications

Dietary choices play a key role in insulin sensitivity among diabetes patients. An 8-week pilot study was conducted to evaluate whether a mostly plant-based dietary program will lead to improvement in biochemical markers in adults with diabetes. The dietary program included educational presentations, weekly cooking demonstrations and small group discussions. A sample of thirty-two adults with diabetes (types 1 and 2) were recruited and seventeen (53%) completed the study. Matched-pair tests and Fishers exact tests were used to compare the changes in means and proportion of the participants’ responses. There were changes in HbA1c, lipids, CRP (mg/L), cholesterol (mg/dL), HDL …


Ovarian Cancer Epidemiology, Healthcare Access And Disparities (Orchid): Methodology For A Population-Based Study Of Black, Hispanic And White Patients With Ovarian Cancer, Tomi Akinyemiju, April Deveaux, Lauren Wilson, Anjali Gupta, Ashwini Joshi, Malcolm Bevel, Chioma Omeogu, Onyinye Ohamadike, Bin Huang, Maria Pisu, Margaret Liang, Molly Mcfatrich, Erin Daniell, Laura Jane Fish, Kevin Ward, Maria Schymura, Andrew Berchuck, Arnold L. Potosky Oct 2021

Ovarian Cancer Epidemiology, Healthcare Access And Disparities (Orchid): Methodology For A Population-Based Study Of Black, Hispanic And White Patients With Ovarian Cancer, Tomi Akinyemiju, April Deveaux, Lauren Wilson, Anjali Gupta, Ashwini Joshi, Malcolm Bevel, Chioma Omeogu, Onyinye Ohamadike, Bin Huang, Maria Pisu, Margaret Liang, Molly Mcfatrich, Erin Daniell, Laura Jane Fish, Kevin Ward, Maria Schymura, Andrew Berchuck, Arnold L. Potosky

Biostatistics Faculty Publications

INTRODUCTION: Less than 40% of patients with ovarian cancer (OC) in the USA receive stage-appropriate guideline-adherent surgery and chemotherapy. Black patients with cancer report greater depression, pain and fatigue than white patients. Lack of access to healthcare likely contributes to low treatment rates and racial differences in outcomes. The Ovarian Cancer Epidemiology, Healthcare Access and Disparities study aims to characterise healthcare access (HCA) across five specific dimensions-Availability, Affordability, Accessibility, Accommodation and Acceptability-among black, Hispanic and white patients with OC, evaluate the impact of HCA on quality of treatment, supportive care and survival, and explore biological mechanisms that may contribute to …


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 Sep 2021

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 …


Hiv Infection And The Risk Of World Health Organization-Defined Sudden Cardiac Death, Matthew S. Freiberg, Meredith S. Duncan, Charles Alcorn, Chung-Chou H. Chang, Suman Kundu, Asri Mumpuni, Emily K. Smith, Sarah Loch, Annie Bedigian, Eric Vittinghoff, Kaku So-Armah, Priscilla Y. Hsue, Amy C. Justice, Zian H. Tseng Sep 2021

Hiv Infection And The Risk Of World Health Organization-Defined Sudden Cardiac Death, Matthew S. Freiberg, Meredith S. Duncan, Charles Alcorn, Chung-Chou H. Chang, Suman Kundu, Asri Mumpuni, Emily K. Smith, Sarah Loch, Annie Bedigian, Eric Vittinghoff, Kaku So-Armah, Priscilla Y. Hsue, Amy C. Justice, Zian H. Tseng

Biostatistics Faculty Publications

Background

People living with HIV have higher sudden cardiac death (SCD) rates compared with the general population. Whether HIV infection is an independent SCD risk factor is unclear.

Methods and Results

This study evaluated participants from the Veterans Aging Cohort Study, an observational, longitudinal cohort of veterans with and without HIV infection matched 1:2 on age, sex, race/ethnicity, and clinical site. Baseline for this study was a participant's first clinical visit on or after April 1, 2003. Participants were followed through December 31, 2014. Using Cox proportional hazards regression, we assessed whether HIV infection, CD4 cell counts, and/or HIV viral …


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 Sep 2021

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 …


Analysis Of Genetic Variants Associated With Levels Of Immune Modulating Proteins For Impact On Alzheimer’S Disease Risk Reveal A Potential Role For Siglec14, Benjamin C. Shaw, Yuriko Katsumata, James F. Simpson, David W. Fardo, Steven Estus Jun 2021

Analysis Of Genetic Variants Associated With Levels Of Immune Modulating Proteins For Impact On Alzheimer’S Disease Risk Reveal A Potential Role For Siglec14, Benjamin C. Shaw, Yuriko Katsumata, James F. Simpson, David W. Fardo, Steven Estus

Biostatistics Faculty Publications

Genome-wide association studies (GWAS) have identified immune-related genes as risk factors for Alzheimer’s disease (AD), including TREM2 and CD33, frequently passing a stringent false-discovery rate. These genes either encode or signal through immunomodulatory tyrosine-phosphorylated inhibitory motifs (ITIMs) or activation motifs (ITAMs) and govern processes critical to AD pathology, such as inflammation and amyloid phagocytosis. To investigate whether additional ITIM and ITAM-containing family members may contribute to AD risk and be overlooked due to the stringent multiple testing in GWAS, we combined protein quantitative trait loci (pQTL) data from a recent plasma proteomics study with AD associations in a recent …


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 Apr 2021

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 …


Real World Clinicopathologic Observations Of Patients With Metastatic Solid Tumors Receiving Immune Checkpoint Inhibitor Therapy: Analysis From Kentucky Cancer Registry, Aasems Jacob, Jianrong Wu, Jill M. Kolesar, Eric B. Durbin, Aju Mathew, Susanne Arnold, Aman Chauhan Feb 2021

Real World Clinicopathologic Observations Of Patients With Metastatic Solid Tumors Receiving Immune Checkpoint Inhibitor Therapy: Analysis From Kentucky Cancer Registry, Aasems Jacob, Jianrong Wu, Jill M. Kolesar, Eric B. Durbin, Aju Mathew, Susanne Arnold, Aman Chauhan

Biostatistics Faculty Publications

The state of Kentucky has the highest cancer incidence and mortality in the United States. High‐risk populations such as this are often underrepresented in clinical trials. The study aims to do a comprehensive analysis of molecular landscape of metastatic cancers among these patients with detailed evaluation of factors affecting response and outcomes to immune checkpoint inhibitor (ICI) therapy. We performed a retrospective analysis of metastatic solid tumor patients who received ICI and underwent molecular profiling at our institution.

Sixty nine patients with metastatic solid tumors who received ICI were included in the study. Prevalence of smoking and secondhand tobacco exposure …


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 Feb 2021

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 Nov 2020

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 Jun 2019

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 …


Measurement Of Bystander Actions In Violence Intervention Evaluation: Opportunities And Challenges, Heather M. Bush, Samuel C. Bell, Ann L. Coker May 2019

Measurement Of Bystander Actions In Violence Intervention Evaluation: Opportunities And Challenges, Heather M. Bush, Samuel C. Bell, Ann L. Coker

Biostatistics Faculty Publications

Purpose of Review

This review discusses design and methodological challenges specific to measuring bystander actions in the evaluation of bystander-based violence prevention programming. “Bystanders” are defined as people who are present immediately before, during and/or after a violent event, but are not a perpetrator nor the intended victim. Bystander-based violence prevention programs seek to prevent or mitigate violent events by empowering bystanders to intervene on acts of violence and social norms that promulgate violence.

Recent Findings

Effective bystander-based violence prevention programs demonstrate increased bystander intentions, actions, and attitudes [Bringing in the Bystander: Banyard et al. J Community Psychol. 2007;35:463-481; iSCREAM: …


Incorporating Pathway Information Into Feature Selection Towards Better Performed Gene Signatures, Suyan Tian, Chi Wang, Bing Wang Apr 2019

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, …


Dichotomous Scoring Of Tdp-43 Proteinopathy From Specific Brain Regions In 27 Academic Research Centers: Associations With Alzheimer's Disease And Cerebrovascular Disease Pathologies, Yuriko Katsumata, David W. Fardo, Walter A. Kukull, Peter T. Nelson Dec 2018

Dichotomous Scoring Of Tdp-43 Proteinopathy From Specific Brain Regions In 27 Academic Research Centers: Associations With Alzheimer's Disease And Cerebrovascular Disease Pathologies, Yuriko Katsumata, David W. Fardo, Walter A. Kukull, Peter T. Nelson

Biostatistics Faculty Publications

TAR-DNA binding protein 43 (TDP-43) proteinopathy is a common brain pathology in elderly persons, but much remains to be learned about this high-morbidity condition. Published stage-based systems for operationalizing disease severity rely on the involvement (presence/absence) of pathology in specific anatomic regions. To examine the comorbidities associated with TDP-43 pathology in aged individuals, we studied data from the National Alzheimer’s Coordinating Center (NACC) Neuropathology Data Set. Data were analyzed from 929 included subjects with available TDP-43 pathology information, sourced from 27 different American Alzheimer’s Disease Centers (ADCs). Cases with relatively unusual diseases including autopsy-proven frontotemporal lobar degeneration (FTLD-TDP or FTLD-tau) …


Serum Nutrient Levels And Aging Effects On Periodontitis, Jeffrey L Ebersole, Joshua Lambert, Heather Bush, Pinar Emecen Huja, Arpita Basu Dec 2018

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. …


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 Oct 2018

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 …


Gaw20: Methods And Strategies For The New Frontiers Of Epigenetics And Pharmacogenomics, Nathan L. Tintle, David W. Fardo, Marzia De Andrade, Stella Aslibekyan, Julia N. Bailey, Justo Lorenzo Bermejo, Rita M. Cantor, Saurabh Ghosh, Philip Melton, Xuexua Wang, Jean W. Maccluer, Laura Almasy Sep 2018

Gaw20: Methods And Strategies For The New Frontiers Of Epigenetics And Pharmacogenomics, Nathan L. Tintle, David W. Fardo, Marzia De Andrade, Stella Aslibekyan, Julia N. Bailey, Justo Lorenzo Bermejo, Rita M. Cantor, Saurabh Ghosh, Philip Melton, Xuexua Wang, Jean W. Maccluer, Laura Almasy

Biostatistics Faculty Publications

GAW20 provided a platform for developing and evaluating statistical methods to analyze human lipid-related phenotypes, DNA methylation, and single-nucleotide markers in a study involving a pharmaceutical intervention. In this article, we present an overview of the data sets and the contributions analyzing these data. The data, donated by the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN) investigators, included data from 188 families (N = 1105) which included genome-wide DNA methylation data before and after a 3-week treatment with fenofibrate, single-nucleotide polymorphisms, metabolic syndrome components before and after treatment, and a variety of covariates. The contributions from individual …


Treatment And Outcomes Of Non-Small-Cell Lung Cancer Patients With High Comorbidity, Jorge Rios, Rahul Gosain, Bernardo H. L. Goulart, Bin Huang, Margaret N. Oechsli, Jaclyn K. Mcdowell, Quan Chen, Thomas Tucker, Goetz H. Kloecker Jan 2018

Treatment And Outcomes Of Non-Small-Cell Lung Cancer Patients With High Comorbidity, Jorge Rios, Rahul Gosain, Bernardo H. L. Goulart, Bin Huang, Margaret N. Oechsli, Jaclyn K. Mcdowell, Quan Chen, Thomas Tucker, Goetz H. Kloecker

Biostatistics Faculty Publications

Background: The life expectancy of untreated non-small-cell lung cancer (NSCLC) is dismal, while treatment for NSCLC improves survival. The presence of comorbidities is thought to play a significant role in the decision to treat or not treat a given patient. We aim to evaluate the association of comorbidities with the survival of patients treated for NSCLC.

Methods: We performed a retrospective study of patients aged ≥66 years with invasive NSCLC between the years 2007 and 2011 in the Surveillance, Epidemiology, and End Results Kentucky Cancer Registry. Comorbidity was measured using the Klabunde Comorbidity Index (KCI), and univariate and multivariate logistic …


Bayesian Prediction Intervals For Assessing P-Value Variability In Prospective Replication Studies, Olga A. Vsevolozhskaya, Gabriel Ruiz, Dmitri Zaykin Dec 2017

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 Oct 2017

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 Sep 2017

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 Aug 2017

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 Jul 2017

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 Jun 2017

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 May 2017

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 Apr 2017

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 Apr 2017

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 Mar 2017

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 Mar 2017

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 …


Inter-Relationships Linking Probability Of Becoming A Case Of Nicotine Dependence With Frequency Of Tobacco Cigarette Smoking, Olga A. Vsevolozhskaya, James C. Anthony Dec 2016

Inter-Relationships Linking Probability Of Becoming A Case Of Nicotine Dependence With Frequency Of Tobacco Cigarette Smoking, Olga A. Vsevolozhskaya, James C. Anthony

Biostatistics Faculty Publications

INTRODUCTION: Once smoking starts, some tobacco cigarette smokers (TCS) can make very rapid transitions into tobacco dependence syndromes (TCD). With adjustment for smoking frequency, we posit female excess risk for this rapid-onset TCD. In a novel application of functional analysis for tobacco research, we estimate four Hill function parameters and plot TCD risk against a gradient of smoking frequency, as observed quite soon after smoking onset.

METHODS: In aggregate, the National Surveys of Drug Use and Health, 2004-2013, identified 1546 newly incident TCS in cross-sectional research, each with standardized TCD assessment.

RESULTS: Hill function estimates contradict our apparently over-simplistic hypothesis. …