Biostatistics Commons^™

Dach1 Mutation Frequency In Endometrial Cancer Is Associated With High Tumor Mutation Burden, Mckayla J. Riggs, Nan Lin, Chi Wang, Dava W. Piecoro, Rachel W. Miller, Oliver A. Hampton, Mahadev Rao, Frederick R. Ueland, Jill M. Kolesar

Obstetrics and Gynecology Faculty Publications

OBJECTIVE: DACH1 is a transcriptional repressor and tumor suppressor gene frequently mutated in melanoma, bladder, and prostate cancer. Loss of DACH1 expression is associated with poor prognostic features and reduced overall survival in uterine cancer. In this study, we utilized the Oncology Research Information Exchange Network (ORIEN) Avatar database to determine the frequency of DACH1 mutations in patients with endometrial cancer in our Kentucky population.

METHODS: We obtained clinical and genomic data for 65 patients with endometrial cancer from the Markey Cancer Center (MCC). We examined the clinical attributes of the cancers by DACH1 status by comparing whole-exome sequencing (WES), …

Bayesian Semi-Supervised Keyphrase Extraction And Jackknife Empirical Likelihood For Assessing Heterogeneity In Meta-Analysis, Guanshen Wang

Statistical Science Theses and Dissertations

This dissertation investigates: (1) A Bayesian Semi-supervised Approach to Keyphrase Extraction with Only Positive and Unlabeled Data, (2) Jackknife Empirical Likelihood Confidence Intervals for Assessing Heterogeneity in Meta-analysis of Rare Binary Events.

In the big data era, people are blessed with a huge amount of information. However, the availability of information may also pose great challenges. One big challenge is how to extract useful yet succinct information in an automated fashion. As one of the first few efforts, keyphrase extraction methods summarize an article by identifying a list of keyphrases. Many existing keyphrase extraction methods focus on the unsupervised setting, …

Bayesian Modeling For Longitudinal Count Data: Applications In Biomedical Research, Morshed Alam

Theses & Dissertations

Biomedical count data such as the number of seizures for epilepsy patients, number of new tumors at each visit or the number vomiting after each chemo-radiation for the cancer patients are common. Often these counts are measured longitudinally from patients or within clusters in multi-site trials. The Poisson and negative binomial models may not be adequate when data exhibit over or under-dispersion, respectively. On the contrary, a variety of dispersion conditions in count data can be captured by Conway-Maxwell Poisson (CMP) model.

This doctoral dissertation relegates to developing a statistical methodology to model longitudinal count data distributed as CMP via …

Multi-Level Small Area Estimation Based On Calibrated Hierarchical Likelihood Approach Through Bias Correction With Applications To Covid-19 Data, Nirosha Rathnayake

Theses & Dissertations

Small area estimation (SAE) has been widely used in a variety of applications to draw estimates in geographic domains represented as a metropolitan area, district, county, or state. The direct estimation methods provide accurate estimates when the sample size of study participants within each area unit is sufficiently large, but it might not always be realistic to have large sample sizes of study participants when considering small geographical regions. Meanwhile, high dimensional socio-ecological data exist at the community level, providing an opportunity for model-based estimation by incorporating rich auxiliary information at the individual and area levels. Thus, it is critical …

The Effect Of Area Deprivation On Covid-19 Risk In Louisiana, K. C. Madhav, Evrim Oral, Susanne Straif-Bourgeois, Ariane L. Rung, Edward S. Peters

School of Public Health Faculty Publications

Background Louisiana in the summer of 2020 had the highest per capita case count for COVID-19 in the United States and COVID-19 deaths disproportionately affects the African American population. Neighborhood deprivation has been observed to be associated with poorer health outcomes. The purpose of this study was to examine the relationship between neighborhood deprivation and COVID-19 in Louisiana. Methods The Area Deprivation Index (ADI) was calculated and used to classify neighborhood deprivation at the census tract level. A total of 17 US census variables were used to calculate the ADI for each of the 1148 census tracts in Louisiana. The …

Cellphone Laws And Teens' Calling While Driving: Analysis Of Repeated Cross-Sectional Surveys In 2013, 2015, 2017, And 2019, Li Li, Caitlin N. Pope, Rebecca R. Andridge, Julie K. Bower, Guoqing Hu, Motao Zhu

Graduate Center for Gerontology Faculty Publications

BACKGROUND: Distracted driving among teens is a public health and safety concern. Most states in the U.S. have sought to restrict cellphone use while driving by enacting laws. This study examines the difference in prevalence of self-reported calling while driving (CWD) between states with different cellphone bans.

METHODS: Demographics and CWD data were extracted from state Youth Risk Behavior Surveys (YRBS) from 14 states in 2013, 2015, 2017, and 2019. The state YRBS is conducted every 2 years with a representative sample of 9th through 12th grade students attending public school. States were grouped by type of cellphone law(s): no …

Uganda As A Role Model For Pandemic Containment In Africa, Ahmed M. Sarki, Alex Ezeh, Saverio Stranges

Epidemiology and Biostatistics Publications

No abstract provided.

Participatory Video As A Novel Recovery-Oriented Intervention In Early Psychosis: A Pilot Study., Arlene G Macdougall, Sahana Kukan, Elizabeth Price, Sarah Glen, Richelle Bird, Laura Powe, Joshua C. Wiener, Paul H Lysaker, Kelly K Anderson, Ross Mg Norman

Epidemiology and Biostatistics Publications

BACKGROUND: Personal narrative plays an important role in the process of recovery from psychotic illnesses. Participatory video is a novel, active intervention that can be used as a tool for fostering narrative development among people with psychosis.

AIM: To assess the feasibility, acceptability and potential clinical utility of participatory video as an innovative tool for promoting recovery in early psychosis.

METHODS: Ten outpatients of an early psychosis intervention programme were recruited to participate in 13 biweekly workshops to plan, film and produce documentary-style videos of their experiences. Feasibility was measured through recruitment and retention. Acceptability was measured through workshop attendance …

Gene Set Testing By Distance Correlation, Sho-Hsien Su

Graduate Theses and Dissertations

Pathways are the functional building blocks of complex diseases such as cancers. Pathway-level studies may provide insights on some important biological processes. Gene set test is an important tool to study the differential expression of a gene set between two groups, e.g., cancer vs normal. The differential expression of a gene set could be due to the difference in mean, variability, or both. However, most existing gene set tests only target the mean difference but overlook other types of differential expression. In this thesis, we propose to use the recently developed distance correlation for gene set testing. To assess the …

The Impact Of The Diabetes Management Incentive On Diabetes-Related Services: Evidence From Ontario, Canada., Thaksha Thavam, Rose Anne Devlin, Amardeep Thind, Gregory S Zaric, Sisira Sarma

Epidemiology and Biostatistics Publications

Financial incentives have been introduced in several countries to improve diabetes management. In Ontario, the most populous province in Canada, a Diabetes Management Incentive (DMI) was introduced to family physicians practicing in patient enrollment models in 2006. This paper examines the impact of the DMI on diabetes-related services provided to individuals with diabetes in Ontario. Longitudinal health administrative data were obtained for adults diagnosed with diabetes and their family physicians. The study population consisted of two groups: DMI group (patients enrolled with a family physician exposed to DMI for 3 years), and comparison group (patients affiliated with a family physician …

Gardasil Vaccine Trends Within Nevada, California, And The U.S.: A Comparative Study, Karen S. Gutierrez

UNLV Theses, Dissertations, Professional Papers, and Capstones

Despite decreasing incidence in cervical cancer in the U.S., there continues to be an increase in public health concern for cervical cancer worldwide. Recent studies report that individuals are disproportionately affected based on region, sex, and race. Additionally, the human papillomavirus (HPV) attributable cancers may be reduced between 70% and 90% through the universal use of HPV-vaccines. In order to expand current knowledge and implement intervention programs in Nevada, it is critical to examine the associations among the Gardasil vaccine, cervical cancer screening, and adverse events following immunization as well as to understand the different socio-demographic subgroups affected. To our …

Statistical Approaches Of Gene Set Analysis With Quantitative Trait Loci For High-Throughput Genomic Studies., Samarendra Das

Electronic Theses and Dissertations

Recently, gene set analysis has become the first choice for gaining insights into the underlying complex biology of diseases through high-throughput genomic studies, such as Microarrays, bulk RNA-Sequencing, single cell RNA-Sequencing, etc. It also reduces the complexity of statistical analysis and enhances the explanatory power of the obtained results. Further, the statistical structure and steps common to these approaches have not yet been comprehensively discussed, which limits their utility. Hence, a comprehensive overview of the available gene set analysis approaches used for different high-throughput genomic studies is provided. The analysis of gene sets is usually carried out based on …

Modified-Half-Normal Distribution And Different Methods To Estimate Average Treatment Effect., Jingchao Sun

Electronic Theses and Dissertations

This dissertation consists of three projects related to Modified-Half-Normal distribution and causal inference. In my first project, a new distribution called Modified-Half-Normal distribution was introduced. I explored a few of its distributional properties, the procedures for generating random samples based on Bayesian approaches, and the parameter estimation based on the method of moments. The second project deals with the problem of selection bias of average treatment effect (ATE) if we use the observational data. I combined the propensity score based inverse probability of treatment weighting (IPTW) method and the directed acyclic graph (DAG) to solve this problem. The third project …

Aspects Of Causal Inference., John A. Craycroft

Electronic Theses and Dissertations

Observational studies differ from experimental studies in that assignment of subjects to treatments is not randomized but rather occurs due to natural mechanisms, which are usually hidden from researchers. Yet objectives of the two studies are frequently the same: identify the causal – rather than merely associational – relationship between some treatment or exposure and an outcome. The statistical issues that arise in properly analyzing observational data for this goal are numerous and fascinating, and these issues are encompassed in the domain of causal inference. The research presented in this dissertation explores several distinct aspects of causal inference. This dissertation …

Conditional Distance Correlation Test For Gene Expression Level, Dna Methylation Level And Copy Number, Shanshan Zhang

Graduate Theses and Dissertations

Over the past years, efforts have been devoted to the genome-wide analysis of genetic and epigenetic profiles to better understand the underlying biological mechanisms of complex diseases such as cancer. It is of great importance to unravel the complex dependence structure between biological factors, and many conditional dependence tests have been developed to meet this need. The traditional partial correlation method can only capture the linear partial correlation, but not the nonlinear correlation. To overcome this limitation, we propose to use the innovative conditional distance correlation (CDC), which measures the conditional dependence between random vectors and detect nonlinear relations. In …

Direct Questioning Of Sensitive Topics In Public Health Studies: A Simulation Study, Jessica K. Fox, Evrim Oral

Annual Symposium on Biomathematics and Ecology Education and Research

No abstract provided.

Evidence Of Nickel And Other Trace Elements And Their Relationship To Clinical Findings In Acute Mesoamerican Nephropathy: A Case-Control Analysis, Rebecca S. B. Fischer, Jason M. Unrine, Chandan Vangala, Wayne T. Sanderson, Sreedhar Mandayam, Kristy O. Murray

Plant and Soil Sciences Faculty Publications

BACKGROUND: Although there are several hypothesized etiologies of Mesoamerican Nephropathy (MeN), evidence has not yet pointed to the underlying cause. Exposure to various trace elements can cause the clinical features observed in MeN.

METHODS AND FINDINGS: We measured 15 trace elements, including heavy metals, in renal case-patients (n = 18) and healthy controls (n = 36) in a MeN high-risk region of Nicaragua. Toenails clippings from study participants were analyzed using inductively coupled plasma mass spectrometry. A case-control analysis was performed, and concentrations were also analyzed over participant characteristics and clinical parameters. Nickel (Ni) concentrations were significantly higher in toenails …

Development Of A Dna Methylation Multiplex Assay For Body Fluid Identification And Age Determination, Quentin Gauthier

FIU Electronic Theses and Dissertations

For forensic laboratories, the determination of body fluid origin of samples collected at a crime scene are typically presumptive and often destructive. However, given that in certain cases the presence of DNA is not in dispute and rather where the DNA came from is of primary concern, new methodologies are needed. Epigenetic modifications, such as DNA methylation, affect gene expression in every cell of every mammal. These DNA methylation patterns typically are observed as the addition of a methyl group on the 5’ carbon of a cytosine followed by guanine (CpG). Methylation patterns have been observed to change in response …

Implementation And Sustainment Of A Statewide Telemedicine Diabetic Retinopathy Screening Network For Federally Designated Safety-Net Clinics, Ana Bastos De Carvalho, S. Lee Ware, Feitong Lei, Heather M. Bush, Robert Sprang, Eric B. Higgins

Ophthalmology and Visual Science Faculty Publications

CONTEXT: Diabetic retinopathy (DR) is the leading cause of incident blindness among working-age adults in the United States. Federally designated safety-net clinics (FDSC) often serve as point-of-contact for patients least likely to receive recommended DR screenings, creating opportunity for targeted interventions to increase screening access and compliance.

STUDY DESIGN AND METHODS: With such a goal, we implemented and assessed the longitudinal performance of an FDSC-based telemedicine DR screening (TDRS) network of 22 clinical sites providing nonmydriatic fundus photography with remote interpretation and reporting. Retrospective analysis of patient encounters between February 2014 and January 2019 was performed to assess rates of …

Blood Pressure Monitoring Following Individual Carpules Of Anesthetic Utilizing Computer-Controlled Anesthetic Delivery, Kristi M. Soileau, Adam E. Degenova, Qingzhao Yu

School of Dentistry Faculty Publications

To date, no study has evaluated blood pressure following administration of each carpule given for dental procedures using a computerized dental anesthesia system. Blood pressures taken prior to performing invasive periodontal procedures were compared with those readings measured following delivery of each of up to three consecutive carpules of Marcaine or Xylocaine in varying order. Pressure differences were also adjusted for age, sex, race, and whether a prescribed anxiolytic was taken beforehand. Neither systolic nor diastolic blood pressures changed significantly as compared to initial blood pressure readings. However, compared with Whites, Hispanics, and Middle Easterners, Blacks had significantly higher systolic …

Stirring The Pot: Switching From Blended Fee-For-Service To Blended Capitation Models Of Physician Remuneration., Nibene H Somé, Rose Anne Devlin, Nirav Mehta, Gregory S Zaric, Sisira Sarma

Epidemiology and Biostatistics Publications

In Canada's most populous province, Ontario, family physicians may choose between the blended fee-for-service (Family Health Group [FHG]) and blended capitation (Family Health Organization [FHO] payment models). Both models incentivize physicians to provide after-hours (AH) and comprehensive care, but FHO physicians receive a capitation payment per enrolled patient adjusted for age and sex, plus a reduced fee-for-service while FHG physicians are paid by fee-for-service. We develop a theoretical model of physician labor supply with multitasking to predict their behavior under FHG and FHO, and estimable equations are derived to test the predictions empirically. Using health administrative data from 2006 to …

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 …

The Use Of Penalized Regression Analysis To Identify County-Level Demographic And Socioeconomic Variables Predictive Of Increased Covid-19 Cumulative Case Rates In The State Of Georgia, Holly L. Richmond, Joana Tome, Haresh Rochani, Isaac Chun-Hai Fung, Gulzar H. Shah, Jessica S. Schwind

Department of Biostatistics, Epidemiology, and Environmental Health Sciences Faculty Publications

Systemic inequity concerning the social determinants of health has been known to affect morbidity and mortality for decades. Significant attention has focused on the individual-level demographic and co-morbid factors associated with rates and mortality of COVID-19. However, less attention has been given to the county-level social determinants of health that are the main drivers of health inequities. To identify the degree to which social determinants of health predict COVID-19 cumulative case rates at the county-level in Georgia, we performed a sequential, cross-sectional ecologic analysis using a diverse set of socioeconomic and demographic variables. Lasso regression was used to identify variables …

Multi-Ancestry Genome-Wide Association Study Accounting For Gene-Psychosocial Factor Interactions Identifies Novel Loci For Blood Pressure Traits, Daokun Sun, Melissa A. Richard, Soloman K. Musani, Yun Ju Sung, Thomas W. Winkler, Karen Schwander, Jin Fang Chai, Xiuqing Guo, Tuomas O. Kilpeläinen, Dina Vojinovic, Hugues Aschard, Traci M. Bartz, Lawrence F. Bielak, Michael R. Brown, Kumaraswamy Chitrala, Fernando P. Hartwig, Andrea R. V. R. Horimoto, Yongmei Liu, Alisa K. Manning, Raymond Noordam, Donna K. Arnett

Epidemiology and Environmental Health Faculty Publications

Psychological and social factors are known to influence blood pressure (BP) and risk of hypertension and associated cardiovascular diseases. To identify novel BP loci, we carried out genome-wide association meta-analyses of systolic, diastolic, pulse, and mean arterial BP, taking into account the interaction effects of genetic variants with three psychosocial factors: depressive symptoms, anxiety symptoms, and social support. Analyses were performed using a two-stage design in a sample of up to 128,894 adults from five ancestry groups. In the combined meta-analyses of stages 1 and 2, we identified 59 loci (p value < 5e−8), including nine novel BP loci. The novel associations were observed mostly with pulse pressure, with fewer observed with mean arterial pressure. Five novel loci were identified in African ancestry, and all but one showed patterns of interaction with at least one psychosocial factor. Functional annotation of the novel loci supports a major role for genes implicated in the immune response (PLCL2), synaptic function and neurotransmission (LIN7A …

Combating Acquired Resistance To Mapk Inhibitors In Melanoma By Targeting Abl1/2-Mediated Reactivation Of Mek/Erk/Myc Signaling, Rakshamani Tripathi, Zulong Liu, Aditi Jain, Anastasia Lyon, Christina Meeks, Dana Richards, Jinpeng Liu, Daheng He, Chi Wang, Marika Nespi, Andrey Rymar, Peng Wang, Melissa Wilson, Rina Plattner

Pharmacology and Nutritional Sciences Faculty Publications

Metastatic melanoma remains an incurable disease for many patients due to the limited success of targeted and immunotherapies. BRAF and MEK inhibitors reduce metastatic burden for patients with melanomas harboring BRAF mutations; however, most eventually relapse due to acquired resistance. Here, we demonstrate that ABL1/2 kinase activities and/or expression are potentiated in cell lines and patient samples following resistance, and ABL1/2 drive BRAF and BRAF/MEK inhibitor resistance by inducing reactivation of MEK/ERK/MYC signaling. Silencing/inhibiting ABL1/2 blocks pathway reactivation, and resensitizes resistant cells to BRAF/MEK inhibitors, whereas expression of constitutively active ABL1/2 is sufficient to promote resistance. Significantly, nilotinib (2nd generation …

Age-Related Losses In Cardiac Autonomic Activity During A Daytime Nap, Pin-Chun Chen, Negin Sattari, Lauren N. Whitehurst, Sara C. Mednick

Psychology Faculty Publications

In healthy, young individuals, a reduction in cardiovascular output and a shift from sympathetic to parasympathetic (vagal) dominance is observed from wake into stages of nocturnal and daytime sleep. This cardiac autonomic profile, measured by heart rate variability (HRV), has been associated with significant benefits for cardiovascular health. Aging is associated with decreased nighttime sleep quality and lower parasympathetic activity during both sleep and resting. However, it is not known whether age-related dampening of HRV extends to daytime sleep, diminishing the cardiovascular benefits of naps in the elderly. Here, we investigated this question by comparing the autonomic activity profile between …

Incorporation And Measurement Of Uncertainty In Clustered And Spatial Data, Yuan Hong

Theses and Dissertations

Analyzing population representative datasets for local estimation and predictions over time is important for monitoring related public health issues, however, there are many statistical challenges associated with such analyses. Mixed effect models are one of the common options which can incorporate time and spatial effect in the model and related inference is well established.

In the first part of this dissertation, to estimate area-level prevalence using individuallevel data, small area estimation (SAE) with post-stratified mixed effect models were used where sampling weights were also incorporated into it. However, if poststratification which requires more computation effort can improve estimation accuracy is …

Contrasting Cumulative Risk And Multiple Individual Risk Models Of The Relationship Between Adverse Childhood Experiences (Aces) And Adult Health Outcomes, Marianna Lanoue, Brandon George, Deborah L Helitzer, Scott W Keith

College of Population Health Faculty Papers

BACKGROUND: A very large body of research documents relationships between self-reported Adverse Childhood Experiences (srACEs) and adult health outcomes. Despite multiple assessment tools that use the same or similar questions, there is a great deal of inconsistency in the operationalization of self-reported childhood adversity for use as a predictor variable. Alternative conceptual models are rarely used and very limited evidence directly contrasts conceptual models to each other. Also, while a cumulative numeric 'ACE Score' is normative, there are differences in the way it is calculated and used in statistical models. We investigated differences in model fit and performance between the …

Call To Action: Sars-Cov-2 And Cerebrovascular Disorders (Cascade), Shahram Abootalebi, Benjamin M. Aertker, Mohammad Sobhan Andalibi, Negar Asdaghi, Ozlem Aykac, M. Reza Azarpazhooh, M. Cecilia Bahit, Kristian Barlinn, Hamidon Basri, Reza Bavarsad Shahripour, Anna Bersano, Jose Biller, Afshin Borhani-Haghighi, Robert D. Brown, Bruce Cv Campbell, Salvador Cruz-Flores, Deidre Anne De Silva, Mario Di Napoli, Afshin A. Divani, Randall C. Edgell, Johanna T. Fifi, Abdoreza Ghoreishi, Teruyuki Hirano, Keun Sik Hong, Chung Y. Hsu, Josephine F. Huang, Manabu Inoue, Amanda L. Jagolino, Moira Kapral, Hoo Fan Kee, Zafer Keser, Rakesh Khatri

Epidemiology and Biostatistics Publications

Background and purpose: The novel severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2), now named coronavirus disease 2019 (COVID-19), may change the risk of stroke through an enhanced systemic inflammatory response, hypercoagulable state, and endothelial damage in the cerebrovascular system. Moreover, due to the current pandemic, some countries have prioritized health resources towards COVID-19 management, making it more challenging to appropriately care for other potentially disabling and fatal diseases such as stroke. The aim of this study is to identify and describe changes in stroke epidemiological trends before, during, and after the COVID-19 pandemic. Methods: This is an international, multicenter, hospital-based …

Machine Learning Applications For Drug Repurposing, Hansaim Lim

Dissertations, Theses, and Capstone Projects

The cost of bringing a drug to market is astounding and the failure rate is intimidating. Drug discovery has been of limited success under the conventional reductionist model of one-drug-one-gene-one-disease paradigm, where a single disease-associated gene is identified and a molecular binder to the specific target is subsequently designed. Under the simplistic paradigm of drug discovery, a drug molecule is assumed to interact only with the intended on-target. However, small molecular drugs often interact with multiple targets, and those off-target interactions are not considered under the conventional paradigm. As a result, drug-induced side effects and adverse reactions are often neglected …