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2018

Statistics and Probability

University of Kentucky

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Full-Text Articles in Physical Sciences and Mathematics

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) …


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 Dec 2018

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 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. …


A Logitudinal Feature Selection Method Identifies Relevant Genes To Distinguish Complicated Injury And Uncomplicated Injury Over Time, Suyan Tian, Chi Wang, Howard H. Chang Dec 2018

A Logitudinal Feature Selection Method Identifies Relevant Genes To Distinguish Complicated Injury And Uncomplicated Injury Over Time, Suyan Tian, Chi Wang, Howard H. Chang

Biostatistics Faculty Publications

Background: Feature selection and gene set analysis are of increasing interest in the field of bioinformatics. While these two approaches have been developed for different purposes, we describe how some gene set analysis methods can be utilized to conduct feature selection.

Methods: We adopted a gene set analysis method, the significance analysis of microarray gene set reduction (SAMGSR) algorithm, to carry out feature selection for longitudinal gene expression data.

Results: Using a real-world application and simulated data, it is demonstrated that the proposed SAMGSR extension outperforms other relevant methods. In this study, we illustrate that a gene’s expression profiles over …


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 Nov 2018

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) …


Can Maternity Benefits Have Long-Term Effects On Childbearing? Evidence From Soviet Russia, Olga Malkova Oct 2018

Can Maternity Benefits Have Long-Term Effects On Childbearing? Evidence From Soviet Russia, Olga Malkova

Economics Faculty Publications

This paper quantifies the effects of Russia’s 1981 expansion in maternity benefits on completed childbearing. The program provided one year of partially paid parental leave and a small cash transfer upon a child’s birth. I exploit the program’s two-stage implementation and find evidence that women had more children as a result of the program. Fertility rates rose immediately by 8.2% over twelve months. The increase in fertility rates not only persisted for the ten-year duration of the program, but it reflected large increases in higher-order births to older women who already had children before the program started.


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 …


Comprehensive Evaluation Of Treatment And Outcomes Of Low-Grade Diffuse Gliomas, Catherine R. Garcia, Stacey A. Slone, Thomas A. Pittman, William H. St. Clair, Donita D. Lightner, John L. Villano Sep 2018

Comprehensive Evaluation Of Treatment And Outcomes Of Low-Grade Diffuse Gliomas, Catherine R. Garcia, Stacey A. Slone, Thomas A. Pittman, William H. St. Clair, Donita D. Lightner, John L. Villano

Markey Cancer Center Faculty Publications

Background

Low-grade gliomas affect younger adults and carry a favorable prognosis. They include a variety of biological features affecting clinical behavior and treatment. Having no guidelines on treatment established, we aim to describe clinical and treatment patterns of low-grade gliomas across the largest cancer database in the United States.

Methods

We analyzed the National Cancer Database from 2004 to 2015, for adult patients with a diagnosis of World Health Organization grade II diffuse glioma.

Results

We analyzed 13,621 cases with median age of 41 years. Over 56% were male, 88.4% were white, 6.1% were black, and 7.6% Hispanic. The most …


Systemic Immunosuppression And Risk Of Age-Related Macular Degeneration, Harpal S. Sandhu, Joshua Lambert, Yan Xu, Henry J. Kaplan Sep 2018

Systemic Immunosuppression And Risk Of Age-Related Macular Degeneration, Harpal S. Sandhu, Joshua Lambert, Yan Xu, Henry J. Kaplan

Applied Statistics Laboratory Faculty Publications

A local immune response has been implicated in the pathogenesis of age-related macular degeneration (AMD), but it is unclear if systemic immunosuppressive/immunomodulatory therapy (IMT) protects against the onset and/or progression of AMD. We performed a retrospective cohort study using a Cox proportional hazards model of two cohorts. Cohort 1 included patients with stage V chronic kidney disease (CKD) status post kidney transplantation, on at least one IMT agent, and older than 50. Cohort 2 included patients with stage IV or V CKD who had not undergone kidney transplantation, were not on IMT, and were older than 50. The main outcomes …


Association Analyses Of Repeated Measures On Triglyceride And High-Density Lipoprotein Levels: Insights From Gaw20, Saurabh Ghosh, David W. Fardo Sep 2018

Association Analyses Of Repeated Measures On Triglyceride And High-Density Lipoprotein Levels: Insights From Gaw20, Saurabh Ghosh, David W. Fardo

Biostatistics Faculty Publications

Background: The GAW20 group formed on the theme of methods for association analyses of repeated measures comprised 4sets of investigators. The provided “real” data set included genotypes obtained from a human whole-genome association study based on longitudinal measurements of triglycerides (TGs) and high-density lipoprotein in addition to methylation levels before and after administration of fenofibrate. The simulated data set contained 200 replications of methylation levels and posttreatment TGs, mimicking the real data set.

Results: The different investigators in the group focused on the statistical challenges unique to family-based association analyses of phenotypes measured longitudinally and applied a wide spectrum of …


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 …


Longitudinal Data Methods For Evaluating Genome-By-Epigenome Interactions In Families, Justin C. Strickland, I-Chen Chen, Chanung Wang, David W. Fardo Sep 2018

Longitudinal Data Methods For Evaluating Genome-By-Epigenome Interactions In Families, Justin C. Strickland, I-Chen Chen, Chanung Wang, David W. Fardo

Psychology Faculty Publications

Background: Longitudinal measurement is commonly employed in health research and provides numerous benefits for understanding disease and trait progression over time. More broadly, it allows for proper treatment of correlated responses within clusters. We evaluated 3 methods for analyzing genome-by-epigenome interactions with longitudinal outcomes from family data.

Results: Linear mixed-effect models, generalized estimating equations, and quadratic inference functions were used to test a pharmacoepigenetic effect in 200 simulated posttreatment replicates. Adjustment for baseline outcome provided greater power and more accurate control of Type I error rates than computation of a pre-to-post change score.

Conclusions: Comparison of all modeling approaches indicated …


Latent Tuberculosis Infection Is Associated With Increased Unstimulated Levels Of Interferon-Gamma In Lima, Peru, Moises A. Huaman, David Henson, Paola L. Rondan, Eduardo Ticona, Gustavo Miranda, Richard J. Kryscio, Raquel Mugruza, Ernesto Aranda, Cesar Ticona, Susan Abarca, Paula Heredia, Andres Aguirre, Timothy R. Sterling, Beth A. Garvy, Carl J. Fichtenbaum Sep 2018

Latent Tuberculosis Infection Is Associated With Increased Unstimulated Levels Of Interferon-Gamma In Lima, Peru, Moises A. Huaman, David Henson, Paola L. Rondan, Eduardo Ticona, Gustavo Miranda, Richard J. Kryscio, Raquel Mugruza, Ernesto Aranda, Cesar Ticona, Susan Abarca, Paula Heredia, Andres Aguirre, Timothy R. Sterling, Beth A. Garvy, Carl J. Fichtenbaum

Internal Medicine Faculty Publications

Background

We previously reported increased unstimulated blood levels of interferon-gamma in persons with latent tuberculosis infection (LTBI) in the United States, suggesting enhanced immune activation in LTBI. To investigate this further in a TB-endemic setting, we assessed interferon-gamma levels in persons with and without LTBI in Peru.

Methods

We analyzed data from patients with and without a recent type 1 (spontaneous) acute myocardial infarction (AMI) who were enrolled from two public hospital networks in Lima, Peru, and underwent LTBI testing using the QuantiFERON® TB Gold In-tube (QFT) assay. Participants with a positive QFT test were defined as having LTBI, whereas …


Effects Of The Affordable Care Act On Health Care Access And Self-Assessed Health After 3 Years, Charles J. Courtemanche, James Marton, Benjamin Ukert, Aaron Yelowitz, Daniela Zapata Sep 2018

Effects Of The Affordable Care Act On Health Care Access And Self-Assessed Health After 3 Years, Charles J. Courtemanche, James Marton, Benjamin Ukert, Aaron Yelowitz, Daniela Zapata

Economics Faculty Publications

Using data from the Behavioral Risk Factor Surveillance System, we examine the causal impact of the Affordable Care Act on health-related outcomes after 3 years. We estimate difference-in-difference-in-differences models that exploit variation in treatment intensity from 2 sources: (1) local area prereform uninsured rates from 2013 and (2) state participation in the Medicaid expansion. Including the third postreform year leads to 2 important insights. First, gains in health insurance coverage and access to care from the policy continued to increase in the third year. Second, an improvement in the probability of reporting excellent health emerged in the third year, with …


P-Value Histograms: Inference And Diagnostics, Patrick Breheny, Arnold Stromberg, Joshua Lambert Aug 2018

P-Value Histograms: Inference And Diagnostics, Patrick Breheny, Arnold Stromberg, Joshua Lambert

Statistics Faculty Publications

It is increasingly common for experiments in biology and medicine to involve large numbers of hypothesis tests. A natural graphical method for visualizing these tests is to construct a histogram from the p-values of these tests. In this article, we examine the shapes, both regular and irregular, that these histograms can take on, as well as present simple inferential procedures that help to interpret the shapes in terms of diagnosing potential problems with the experiment. We examine potential causes of these problems in detail, and discuss potential remedies. Throughout, examples of irregular-looking p-value histograms are provided and based …


A Programme For Risk Assessment And Minimisation Of Progressive Multifocal Leukoencephalopathy Developed For Vedolizumab Clinical Trials, Asit Parikh, Kristin Stephens, Eugene Major, Irving Fox, Catherine Milch, Serap Sankoh, Michael H. Lev, James M. Provenzale, Jesse Shick, Mark Patti, Megan Mcauliffe, Joseph R. Berger, David B. Clifford Aug 2018

A Programme For Risk Assessment And Minimisation Of Progressive Multifocal Leukoencephalopathy Developed For Vedolizumab Clinical Trials, Asit Parikh, Kristin Stephens, Eugene Major, Irving Fox, Catherine Milch, Serap Sankoh, Michael H. Lev, James M. Provenzale, Jesse Shick, Mark Patti, Megan Mcauliffe, Joseph R. Berger, David B. Clifford

Neurology Faculty Publications

Introduction Over the past decade, the potential for drug-associated progressive multifocal leukoencephalopathy (PML) has become an increasingly important consideration in certain drug development programmes, particularly those of immunomodulatory biologics. Whether the risk of PML with an investigational agent is proven (e.g. extrapolated from relevant experience, such as a class effect) or merely theoretical, the serious consequences of acquiring PML require careful risk minimisation and assessment. No single standard for such risk minimisation exists. Vedolizumab is a recently developed monoclonal antibody to α4β7 integrin. Its clinical development necessitated a dedicated PML risk minimisation assessment as part of a global preapproval regulatory …


Low-Fat Abiraterone Food Effect Is Of Little Consequence, Jill M. Kolesar, Glenn X. Liu May 2018

Low-Fat Abiraterone Food Effect Is Of Little Consequence, Jill M. Kolesar, Glenn X. Liu

Pharmacy Practice and Science Faculty Publications

No abstract provided.


The Influence Of Parental Control And Parent-Child Relational Qualities On Adolescent Internet Addiction: A 3-Year Longitudinal Study In Hong Kong, Daniel T. L. Shek, Xiaoqin Zhu, Cecilia M. S. Ma May 2018

The Influence Of Parental Control And Parent-Child Relational Qualities On Adolescent Internet Addiction: A 3-Year Longitudinal Study In Hong Kong, Daniel T. L. Shek, Xiaoqin Zhu, Cecilia M. S. Ma

Pediatrics Faculty Publications

This study investigated how parental behavioral control, parental psychological control, and parent-child relational qualities predicted the initial level and rate of change in adolescent internet addiction (IA) across the junior high school years. The study also investigated the concurrent and longitudinal effects of different parenting factors on adolescent IA. Starting from the 2009/2010 academic year, 3,328 Grade 7 students (Mage = 12.59 ± 0.74 years) from 28 randomly selected secondary schools in Hong Kong responded on a yearly basis to a questionnaire measuring multiple constructs including socio-demographic characteristics, perceived parenting characteristics, and IA. Individual growth curve (IGC) analyses …


Evaluating Preexisting Qualitative Research Data For Secondary Analysis, Victoria Sherif May 2018

Evaluating Preexisting Qualitative Research Data For Secondary Analysis, Victoria Sherif

Educational Leadership Studies Faculty Publications

In this article, I explore the nature of secondary analysis and provide a brief history of the method. Qualitative secondary analysis is a relatively under-used method in education and the social sciences, often due to the lack of easily accessible, relevant, trustworthy, and complete data. I address some of the potentials and limitations that influence its use and explore criteria for assessing the quality and sufficiency of preexisting qualitative research data. Qualitative secondary analysis has important implications for qualitative researchers, students and practitioners interested in generating new knowledge via unobtrusive, reliable, valid, and time/cost effective research through the wider use …


Quality Of Life During Treatment With Chemohormonal Therapy: Analysis Of E3805 Chemohormonal Androgen Ablation Randomized Trial In Prostate Cancer, Alicia K. Morgans, Yu-Hui Chen, Christopher J. Sweeney, David F. Jarrard, Elizabeth R. Plimack, Benjamin A. Gartrell, Michael A. Carducci, Maha Hussain, Jorge A. Garcia, David Cella, Robert S. Dipaola, Linda J. Patrick-Miller Apr 2018

Quality Of Life During Treatment With Chemohormonal Therapy: Analysis Of E3805 Chemohormonal Androgen Ablation Randomized Trial In Prostate Cancer, Alicia K. Morgans, Yu-Hui Chen, Christopher J. Sweeney, David F. Jarrard, Elizabeth R. Plimack, Benjamin A. Gartrell, Michael A. Carducci, Maha Hussain, Jorge A. Garcia, David Cella, Robert S. Dipaola, Linda J. Patrick-Miller

Internal Medicine Faculty Publications

Purpose

Chemohormonal therapy with docetaxel and androgen deprivation therapy (ADT+D) for metastatic hormone-sensitive prostate cancer improves overall survival as compared with androgen deprivation therapy (ADT) alone. We compared the quality of life (QOL) between patients with metastatic hormone-sensitive prostate cancer who were treated with ADT+D and those who were treated with ADT alone.

Methods

Men were randomly assigned to ADT+ D (six cycles) or to ADT alone. QOL was assessed by Functional Assessment of Cancer Therapy-Prostate (FACT-P), FACT-Taxane, Functional Assessment of Chronic Illness Therapy-Fatigue, and the Brief Pain Inventory at baseline and at 3, 6, 9, and 12 months. The …


Self-Reported Risk And Delinquent Behavior And Problem Behavioral Intention In Hong Kong Adolescents: The Role Of Moral Competence And Spirituality, Daniel T. L. Shek, Xiaoqin Zhu Mar 2018

Self-Reported Risk And Delinquent Behavior And Problem Behavioral Intention In Hong Kong Adolescents: The Role Of Moral Competence And Spirituality, Daniel T. L. Shek, Xiaoqin Zhu

Pediatrics Faculty Publications

Based on the six-wave data collected from Grade 7 to Grade 12 students (N = 3,328 at Wave 1), this pioneer study examined the development of problem behaviors (risk and delinquent behavior and problem behavioral intention) and the predictors (moral competence and spirituality) among adolescents in Hong Kong. Individual growth curve models revealed that while risk and delinquent behavior accelerated and then slowed down in the high school years, adolescent problem behavioral intention slightly accelerated over time. After controlling the background socio-demographic factors, moral competence and spirituality were negatively associated with risk and delinquent behavior as well as problem …


Telotristat Ethyl In Carcinoid Syndrome: Safety And Efficacy In The Telecast Phase 3 Trial, Marianne Pavel, David J. Gross, Marta Benavent, Petros Perros, Raj Srirajaskanthan, Richard R. P. Warner, Matthew H. Kulke, Lowell B. Anthony, Pamela L. Kunz, Dieter Hörsch, Martin O Weickert, Pablo Lapuerta, Wenjun Jiang, Kenneth Kassler-Taub, Suman Wason, Rosanna Fleming, Douglas Fleming, Rocio Garcia-Carbonero Mar 2018

Telotristat Ethyl In Carcinoid Syndrome: Safety And Efficacy In The Telecast Phase 3 Trial, Marianne Pavel, David J. Gross, Marta Benavent, Petros Perros, Raj Srirajaskanthan, Richard R. P. Warner, Matthew H. Kulke, Lowell B. Anthony, Pamela L. Kunz, Dieter Hörsch, Martin O Weickert, Pablo Lapuerta, Wenjun Jiang, Kenneth Kassler-Taub, Suman Wason, Rosanna Fleming, Douglas Fleming, Rocio Garcia-Carbonero

Internal Medicine Faculty Publications

Telotristat ethyl, a tryptophan hydroxylase inhibitor, was efficacious and well tolerated in the phase 3 TELESTAR study in patients with carcinoid syndrome (CS) experiencing ≥ 4 bowel movements per day (BMs/day) while on somatostatin analogs (SSAs). TELECAST, a phase 3 companion study, assessed the safety and efficacy of telotristat ethyl in patients with CS (diarrhea, flushing, abdominal pain, nausea or elevated urinary 5-hydroxyindoleacetic acid (u5-HIAA)) with < 4 BMs/day on SSAs (or ≥ 1 symptom or ≥ 4 BMs/day if not on SSAs) during a 12-week double-blind treatment period followed by a 36-week open-label extension (OLE). The primary safety and efficacy endpoints were incidence of treatment-emergent adverse events (TEAEs) and percent change from baseline in 24-h u5-HIAA at week 12. Patients (N = 76) were randomly assigned (1:1:1) to receive placebo or telotristat ethyl 250 mg or 500 mg 3 times per day (tid); 67 continued receiving telotristat ethyl 500 mg tid during the OLE. …


Motivators For Alzheimer's Disease Clinical Trial Participation, Shoshana H. Bardach, Sarah D. Holmes, Gregory A. Jicha Feb 2018

Motivators For Alzheimer's Disease Clinical Trial Participation, Shoshana H. Bardach, Sarah D. Holmes, Gregory A. Jicha

Graduate Center for Gerontology Faculty Publications

Background

Alzheimer’s disease (AD) research progress is impeded due to participant recruitment challenges. This study seeks to better understand, from the perspective of individuals engaged in clinical trials (CTs), research motivations.

Methods

Participants, or their caregivers, from AD treatment and prevention CTs were surveyed about research motivators.

Results

The 87 respondents had a mean age of 72.2, were predominantly Caucasian, 55.2% were male, and 56.3% had cognitive impairment. An overwhelming majority rated the potential to help themselves or a loved one and the potential to help others in the future as important motivators. Relatively few respondents were motivated by free …


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 Feb 2018

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 …


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 …


Improved Methods And Selecting Classification Types For Time-Dependent Covariates In The Marginal Analysis Of Longitudinal Data, I-Chen Chen Jan 2018

Improved Methods And Selecting Classification Types For Time-Dependent Covariates In The Marginal Analysis Of Longitudinal Data, I-Chen Chen

Theses and Dissertations--Epidemiology and Biostatistics

Generalized estimating equations (GEE) are popularly utilized for the marginal analysis of longitudinal data. In order to obtain consistent regression parameter estimates, these estimating equations must be unbiased. However, when certain types of time-dependent covariates are presented, these equations can be biased unless an independence working correlation structure is employed. Moreover, in this case regression parameter estimation can be very inefficient because not all valid moment conditions are incorporated within the corresponding estimating equations. Therefore, approaches using the generalized method of moments or quadratic inference functions have been proposed for utilizing all valid moment conditions. However, we have found that …


Multifactor Dimensionality Reduction With P Risk Scores Per Person, Ye Li Jan 2018

Multifactor Dimensionality Reduction With P Risk Scores Per Person, Ye Li

Theses and Dissertations--Statistics

After reviewing Multifactor Dimensionality Reduction(MDR) and its extensions, an approach to obtain P(larger than 1) risk scores is proposed to predict the continuous outcome for each subject. We study the mean square error(MSE) of dimensionality reduced models fitted with sets of 2 risk scores and investigate the MSE for several special cases of the covariance matrix. A methodology is proposed to select a best set of P risk scores when P is specified a priori. Simulation studies based on true models of different dimensions(larger than 3) demonstrate that the selected set of P(larger than 1) risk scores outperforms the single …


Modeling And Mapping Location-Dependent Human Appearance, Zachary Bessinger Jan 2018

Modeling And Mapping Location-Dependent Human Appearance, Zachary Bessinger

Theses and Dissertations--Computer Science

Human appearance is highly variable and depends on individual preferences, such as fashion, facial expression, and makeup. These preferences depend on many factors including a person's sense of style, what they are doing, and the weather. These factors, in turn, are dependent upon geographic location and time. In our work, we build computational models to learn the relationship between human appearance, geographic location, and time. The primary contributions are a framework for collecting and processing geotagged imagery of people, a large dataset collected by our framework, and several generative and discriminative models that use our dataset to learn the relationship …


Occurrence And Attributes Of Two Echinoderm-Bearing Faunas From The Upper Mississippian (Chesterian; Lower Serpukhovian) Ramey Creek Member, Slade Formation, Eastern Kentucky, U.S.A., Ann Well Harris Jan 2018

Occurrence And Attributes Of Two Echinoderm-Bearing Faunas From The Upper Mississippian (Chesterian; Lower Serpukhovian) Ramey Creek Member, Slade Formation, Eastern Kentucky, U.S.A., Ann Well Harris

Theses and Dissertations--Earth and Environmental Sciences

Well-preserved echinoderm faunas are rare in the fossil record, and when uncovered, understanding their occurrence can be useful in interpreting other faunas. In this study, two such faunas of the same age from separate localities in the shallow-marine Ramey Creek Member of the Slade Formation in the Upper Mississippian (Chesterian) rocks of eastern Kentucky are examined. Of the more than 5,000 fossil specimens from both localities, only 9–34 percent were echinoderms from 3–5 classes. Nine non-echinoderm (8 invertebrate and one vertebrate) classes occurred at both localities, but of these, bryozoans, brachiopods and sponges dominated. To understand the attributes of both …


Categorizing A Continuous Predictor Subject To Measurement Error, Betsabé G. Blas Achic, Tianying Wang, Ya Su, Victor Kipnis, Kevin Dodd, Raymond J. Carroll Jan 2018

Categorizing A Continuous Predictor Subject To Measurement Error, Betsabé G. Blas Achic, Tianying Wang, Ya Su, Victor Kipnis, Kevin Dodd, Raymond J. Carroll

Statistics Faculty Publications

Epidemiologists often categorize a continuous risk predictor, even when the true risk model is not a categorical one. Nonetheless, such categorization is thought to be more robust and interpretable, and thus their goal is to fit the categorical model and interpret the categorical parameters. We address the question: with measurement error and categorization, how can we do what epidemiologists want, namely to estimate the parameters of the categorical model that would have been estimated if the true predictor was observed? We develop a general methodology for such an analysis, and illustrate it in linear and logistic regression. Simulation studies are …