Statistics and Probability Commons^™

Bayesian Kinetic Modeling For Tracer-Based Metabolomic Data, Xu Zhang

Theses and Dissertations--Statistics

Kinetic modeling of the time dependence of metabolite concentrations including the unstable isotope labeled species is an important approach to simulate metabolic pathway dynamics. It is also essential for quantitative metabolic flux analysis using tracer data. However, as the metabolic networks are complex including extensive compartmentation and interconnections, the parameter estimation for enzymes that catalyze individual reactions needed for kinetic modeling is challenging. As the pa- rameter space is large and multi-dimensional while kinetic data are comparatively sparse, the estimation procedure (especially the point estimation methods) often en- counters multiple local maximum such that standard maximum likelihood methods may yield …

Statistical Intervals For Various Distributions Based On Different Inference Methods, Yixuan Zou

Theses and Dissertations--Statistics

Statistical intervals (e.g., confidence, prediction, or tolerance) are widely used to quantify uncertainty, but complex settings can create challenges to obtain such intervals that possess the desired properties. My thesis will address diverse data settings and approaches that are shown empirically to have good performance. We first introduce a focused treatment on using a single-layer bootstrap calibration to improve the coverage probabilities of two-sided parametric tolerance intervals for non-normal distributions. We then turn to zero-inflated data, which are commonly found in, among other areas, pharmaceutical and quality control applications. However, the inference problem often becomes difficult in the presence of …

Moment Kernels For T-Central Subspace, Weihang Ren

Theses and Dissertations--Statistics

The T-central subspace allows one to perform sufficient dimension reduction for any statistical functional of interest. We propose a general estimator using a third moment kernel to estimate the T-central subspace. In particular, in this dissertation we develop sufficient dimension reduction methods for the central mean subspace via the regression mean function and central subspace via Fourier transform, central quantile subspace via quantile estimator and central expectile subsapce via expectile estima- tor. Theoretical results are established and simulation studies show the advantages of our proposed methods.

Measuring Change: Prediction Of Early Onset Sepsis, Aric Schadler

Theses and Dissertations--Statistics

Sepsis occurs in a patient when an infection enters into the blood stream and spreads throughout the body causing a cascading response from the immune system. Sepsis is one of the leading causes of morbidity and mortality in today’s hospitals. This is despite published and accepted guidelines for timely and appropriate interventions for septic patients. The largest barrier to applying these interventions is the early identification of septic patients. Early identification and treatment leads to better outcomes, shorter lengths of stay, and financial savings for healthcare institutions. In order to increase the lead time in recognizing patients trending towards septicemia …

Simultaneous Tolerance Intervals For Response Surface And Mixture Designs Using The Adjusted Product Set Method, Aisaku Nakamura

Theses and Dissertations--Statistics

Various methods for constructing simultaneous tolerance intervals for regression models have been developed over the years, but all of them can be shown to be conservative. In this thesis, extensive simulations are conducted to evaluate the degree of conservatism with respect to their coverage probabilities. A new strategy to fit simultaneous tolerance intervals on linear models is proposed by modifying an existing method, which we call the adjusted product set (APS) method. The APS method will also be used to construct simultaneous tolerance bands on response surface and mixture designs.

Impact Of Motor Therapy With Dynamic Body-Weight Support On Functional Independence Measures In Traumatic Brain Injury: An Exploratory Study, Emily F. Anggelis, Elizabeth Salmon Powell, Philip M. Westgate, Amanda C. Glueck, Lumy Sawaki

Physical Medicine and Rehabilitation Faculty Publications

BACKGROUND: Contemporary goals of rehabilitation after traumatic brain injury (TBI) aim to improve cognitive and motor function by applying concepts of neuroplasticity. This can be challenging to carry out in TBI patients with motor, balance, and cognitive impairments.

OBJECTIVE: To determine whether use of dynamic body-weight support (DBWS) would allow safe administration of intensive motor therapy during inpatient rehabilitation and whether its use would yield greater improvement in functional recovery than standard-of-care (SOC) therapy in adults with TBI.

METHODS: Data in this retrospective cohort study was collected from patients with TBI who receive inpatient rehabilitation incorporating DBWS (n = …

Chronic Muscle Weakness And Mitochondrial Dysfunction In The Absence Of Sustained Atrophy In A Preclinical Sepsis Model, Allison M. Owen, Samir P. Patel, Jeffrey D. Smith, Beverly K. Balasuriya, Stephanie F. Mori, Gregory S. Hawk, Arnold J. Stromberg, Naohide Kuriyama, Masao Kaneki, Alexander G. Rabchevsky, Timothy A. Butterfield, Karyn A. Esser, Charlotte A. Peterson, Marlene E. Starr, Hiroshi Saito

Physiology Faculty Publications

Chronic critical illness is a global clinical issue affecting millions of sepsis survivors annually. Survivors report chronic skeletal muscle weakness and development of new functional limitations that persist for years. To delineate mechanisms of sepsis-induced chronic weakness, we first surpassed a critical barrier by establishing a murine model of sepsis with ICU-like interventions that allows for the study of survivors. We show that sepsis survivors have profound weakness for at least 1 month, even after recovery of muscle mass. Abnormal mitochondrial ultrastructure, impaired respiration and electron transport chain activities, and persistent protein oxidative damage were evident in the muscle of …

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 …

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 …

Metformin Blunts Muscle Hypertrophy In Response To Progressive Resistance Exercise Training In Older Adults: A Randomized, Double‐Blind, Placebo‐Controlled, Multicenter Trial: The Masters Trial, R. Grace Walton, Cory M. Dungan, Douglas E. Long, S. Craig Tuggle, Kate Kosmac, Bailey D. Peck, Heather M. Bush, Alejandro G. Villasante Tezanos, Gerald Mcgwin, Samuel T. Windham, Fernando Ovalle, Marcas M. Bamman, Philip A. Kern, Charlotte A. Peterson

Center for Muscle Biology Faculty Publications

Progressive resistance exercise training (PRT) is the most effective known intervention for combating aging skeletal muscle atrophy. However, the hypertrophic response to PRT is variable, and this may be due to muscle inflammation susceptibility. Metformin reduces inflammation, so we hypothesized that metformin would augment the muscle response to PRT in healthy women and men aged 65 and older. In a randomized, double-blind trial, participants received 1,700 mg/day metformin (N = 46) or placebo (N = 48) throughout the study, and all subjects performed 14 weeks of supervised PRT. Although responses to PRT varied, placebo gained more lean body …

Incidence And Cost Of Acute Kidney Injury In Hospitalized Patients With Infective Endocarditis, Victor M. Ortiz-Soriano, Katherine Donaldson, Gaixin Du, Ye Li, Joshua Lambert, Dan Cleland, Alice C. Thornton, Laura C. Fanucchi, Moises A. Huaman, Javier A. Neyra

Internal Medicine Faculty Publications

Acute kidney injury (AKI) is a frequent complication of hospitalized patients with infective endocarditis (IE). Further, AKI in the setting of IE is associated with high morbidity and mortality. We aimed to examine the incidence, clinical parameters, and hospital costs associated with AKI in hospitalized patients with IE in an endemic area with an increasing prevalence of opioid use. This retrospective cohort study included 269 patients admitted to a major referral center in Kentucky with a primary diagnosis of IE from January 2013 to December 2015. Of these, 178 (66.2%) patients had AKI by Kidney Disease Improving Global Outcomes (KDIGO) …

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 …

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 …

Disparities In Prostate Cancer Survival In Appalachian Kentucky: A Population-Based Study, Zin W. Myint, Richard O'Neal, Quan Chen, Bin Huang, Robin C. Vanderpool, Peng Wang

Internal Medicine Faculty Publications

Introduction: Prostate cancer (PC) is the most common male cancer in the USA. When comparing the incidence and mortality rates of PC, the Surveillance Epidemiology and End Results data of 2005–2014 show that Appalachian Kentucky had a lower incidence (113/100 000 v 137/100 000) but a higher mortality rate (23.8% v 21.8%) when compared to non-Appalachian Kentucky. The aim of this study was to further characterize the survival disparities of PC between Appalachian and non-Appalachian Kentucky.

Methods: All stages of PC patients diagnosed between 2007 and 2011 were collected through the Kentucky Cancer Registry. Baseline characteristics and survival outcomes were …

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: …

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, …

Tobacco Smoking And Dementia In A Kentucky Cohort: A Competing Risk Analysis, Erin L. Abner, Peter T. Nelson, Gregory A. Jicha, Gregory E. Cooper, David W. Fardo, Frederick A. Schmitt, Richard J. Kryscio

Epidemiology and Environmental Health Faculty Publications

Tobacco smoking was examined as a risk for dementia and neuropathological burden in 531 initially cognitively normal older adults followed longitudinally at the University of Kentucky’s Alzheimer’s Disease Center. The cohort was followed for an average of 11.5 years; 111 (20.9%) participants were diagnosed with dementia, while 242 (45.6%) died without dementia. At baseline, 49 (9.2%) participants reported current smoking (median pack-years = 47.3) and 231 (43.5%) former smoking (median pack-years = 24.5). The hazard ratio (HR) for dementia for former smokers versus never smokers based on the Cox model was 1.64 (95% CI: 1.09, 2.46), while the HR for …

Feature Selection For Longitudinal Data By Using Sign Averages To Summarize Gene Expression Values Over Time, Suyan Tian, Chi Wang

Biostatistics Faculty Publications

With the rapid evolution of high-throughput technologies, time series/longitudinal high-throughput experiments have become possible and affordable. However, the development of statistical methods dealing with gene expression profiles across time points has not kept up with the explosion of such data. The feature selection process is of critical importance for longitudinal microarray data. In this study, we proposed aggregating a gene’s expression values across time into a single value using the sign average method, thereby degrading a longitudinal feature selection process into a classic one. Regularized logistic regression models with pseudogenes (i.e., the sign average of genes across time as predictors) …

Evaluating Trajectories Of Episodic Memory In Normal Cognition And Mild Cognitive Impairment: Results From Adni, Xiuhua Ding, Richard J. Charnigo, Frederick A. Schmitt, Richard J. Kryscio, Erin L. Abner, Alzheimer’S Disease Neuroimaging Initiative

Statistics Faculty Publications

BACKGROUND: Memory assessment is a key factor for the diagnosis of cognitive impairment. However, memory performance over time may be quite heterogeneous within diagnostic groups.

METHOD: To identify latent trajectories in memory performance and their associated risk factors, we analyzed data from Alzheimer's Disease Neuroimaging Initiative (ADNI) participants who were classified either as cognitively normal or as Mild Cognitive Impairment (MCI) at baseline and were administered the Rey Auditory Verbal Learning test (RAVLT) for up to 9 years. Group-based trajectory modeling on the 30-minute RAVLT delayed recall score was applied separately to the two baseline diagnostic groups.

RESULTS: There were …

Impact Of The Affordable Care Act On Colorectal Cancer Screening, Incidence, And Survival In Kentucky, Tong Gan, Heather F. Sinner, Samuel C. Walling, Quan Chen, Bin Huang, Thomas C. Tucker, Jitesh A. Patel, B. Mark Evers, Avinash S. Bhakta

Surgery Faculty Publications

Background

Kentucky ranks first in the US in cancer incidence and mortality. Compounded by high poverty levels and a high rate of medically uninsured, cancer rates are even worse in Appalachian Kentucky. Being one of the first states to adopt the Affordable Care Act (ACA) Medicaid expansion, insurance coverage markedly increased for Kentucky residents. The purpose of our study was to determine the impact of Medicaid expansion on colorectal cancer (CRC) screening, diagnosis, and survival in Kentucky.

Study Design

The Kentucky Cabinet for Health and Family Services and the Kentucky Cancer Registry were queried for individuals (≥20 years) undergoing CRC …

A Parent-Led Intervention To Promote Recovery Following Pediatric Injury: Study Protocol For A Randomized Controlled Trial, Meghan L. Marsac, Ginny Sprang, Leila Guller, Kristen L. Kohser, John M. Draus Jr., Nancy Kassam-Adams

Pediatrics Faculty Publications

Background: Injury is one of the most prevalent potentially emotionally traumatic events that children experience and can lead to persistent impaired physical and emotional health. There is a need for interventions that promote full physical and emotional recovery and that can be easily accessed by all injured children. Based on research evidence regarding post-injury recovery, we created the Cellie Coping Kit for Children with Injury intervention to target key mechanisms of action and refined the intervention based on feedback from children, families, and experts in the field. The Cellie Coping Kit intervention is parent-guided and includes a toy (for engagement), …

Volleyball Overhead Swing Volume And Injury Frequency Over The Course Of A Season, Heather Wolfe, Katherine Poole, Alejandro G. Villasante Tezanos, Robert A. English, Timothy L. Uhl

Statistics Faculty Publications

Background: Overuse injuries are common in volleyball; however, few studies exist that quantify the workload of a volleyball athlete in a season. The relationship between workload and shoulder injury has not been extensively studied in women's collegiate volleyball athletes.

Hypothesis/Purpose: This study aims to quantify shoulder workloads by counting overhead swings during practice and matches. The purpose of the current study is to provide a complete depiction of typical overhead swings, serves, and hits, which occur in both practices and matches. The primary hypothesis was that significantly more swings will occur in practices compared to matches. The secondary hypothesis was …

The Use Of 3-D Highway Differential Geometry In Crash Prediction Modeling, Kiriakos Amiridis

Theses and Dissertations--Civil Engineering

The objective of this research is to evaluate and introduce a new methodology regarding rural highway safety. Current practices rely on crash prediction models that utilize specific explanatory variables, whereas the depository of knowledge for past research is the Highway Safety Manual (HSM). Most of the prediction models in the HSM identify the effect of individual geometric elements on crash occurrence and consider their combination in a multiplicative manner, where each effect is multiplied with others to determine their combined influence. The concepts of 3-dimesnional (3-D) representation of the roadway surface have also been explored in the past aiming to …

Evaluating The Impacts Of Antidepressant Use On The Risk Of Dementia, Ran Duan

Theses and Dissertations--Epidemiology and Biostatistics

Dementia is a clinical syndrome caused by neurodegeneration or cerebrovascular injury. Patients with dementia suffer from deterioration in memory, thinking, behavior and the ability to perform everyday activities. Since there are no cures or disease-modifying therapies for dementia, there is much interest in identifying modifiable risk factors that may help prevent or slow the progression of cognitive decline. Medications are a common focus of this type of research.

Importantly, according to a report from the Centers for Disease Control and Prevention (CDC), 19.1% of the population aged 60 and over report taking antidepressants during 2011-2014, and this number tends to …

A New Independence Measure And Its Applications In High Dimensional Data Analysis, Chenlu Ke

Theses and Dissertations--Statistics

This dissertation has three consecutive topics. First, we propose a novel class of independence measures for testing independence between two random vectors based on the discrepancy between the conditional and the marginal characteristic functions. If one of the variables is categorical, our asymmetric index extends the typical ANOVA to a kernel ANOVA that can test a more general hypothesis of equal distributions among groups. The index is also applicable when both variables are continuous. Second, we develop a sufficient variable selection procedure based on the new measure in a large p small n setting. Our approach incorporates marginal information between …

Transforms In Sufficient Dimension Reduction And Their Applications In High Dimensional Data, Jiaying Weng

Theses and Dissertations--Statistics

The big data era poses great challenges as well as opportunities for researchers to develop efficient statistical approaches to analyze massive data. Sufficient dimension reduction is such an important tool in modern data analysis and has received extensive attention in both academia and industry.

In this dissertation, we introduce inverse regression estimators using Fourier transforms, which is superior to the existing SDR methods in two folds, (1) it avoids the slicing of the response variable, (2) it can be readily extended to solve the high dimensional data problem. For the ultra-high dimensional problem, we investigate both eigenvalue decomposition and minimum …

Unsupervised Learning In Phylogenomic Analysis Over The Space Of Phylogenetic Trees, Qiwen Kang

Theses and Dissertations--Statistics

A phylogenetic tree is a tree to represent an evolutionary history between species or other entities. Phylogenomics is a new field intersecting phylogenetics and genomics and it is well-known that we need statistical learning methods to handle and analyze a large amount of data which can be generated relatively cheaply with new technologies. Based on the existing Markov models, we introduce a new method, CURatio, to identify outliers in a given gene data set. This method, intrinsically an unsupervised method, can find outliers from thousands or even more genes. This ability to analyze large amounts of genes (even with missing …

Serial Testing For Detection Of Multilocus Genetic Interactions, Zaid T. Al-Khaledi

Theses and Dissertations--Statistics

A method to detect relationships between disease susceptibility and multilocus genetic interactions is the Multifactor-Dimensionality Reduction (MDR) technique pioneered by Ritchie et al. (2001). Since its introduction, many extensions have been pursued to deal with non-binary outcomes and/or account for multiple interactions simultaneously. Studying the effects of multilocus genetic interactions on continuous traits (blood pressure, weight, etc.) is one case that MDR does not handle. Culverhouse et al. (2004) and Gui et al. (2013) proposed two different methods to analyze such a case. In their research, Gui et al. (2013) introduced the Quantitative Multifactor-Dimensionality Reduction (QMDR) that uses the overall …