Biostatistics Commons^™

Integrative Pathway Analysis Pipeline For Mirna And Mrna Data, Diana Mabel Diaz Herrera

Wayne State University Theses

The identification of pathways that are involved in a particular phenotype helps us understand the underlying biological processes. Traditional pathway analysis techniques aim to infer the impact on individual pathways using only mRNA levels. However, recent studies showed that gene expression alone is unable to capture the whole picture of biological phenomena. At the same time, MicroRNAs (miRNAs) are newly discovered gene regulators that have shown to play an important role in diagnosis, and prognosis for different types of diseases. Current pathway analysis techniques do not take miRNAs into consideration. In this project, we investigate the effect of integrating miRNA …

A Predictive Probability Interim Design For Phase Ii Clinical Trials With Continuous Endpoints, Meng Liu

Theses and Dissertations--Epidemiology and Biostatistics

Phase II clinical trials aim to potentially screen out ineffective and identify effective therapies to move forward to randomized phase III trials. Single-arm studies remain the most utilized design in phase II oncology trials, especially in scenarios where a randomized design is simply not practical. Due to concerns regarding excessive toxicity or ineffective new treatment strategies, interim analyses are typically incorporated in the trial, and the choice of statistical methods mainly depends on the type of primary endpoints. For oncology trials, the most common primary objectives in phase II trials include tumor response rate (binary endpoint) and progression disease-free survival …

Statistical Analyses To Detect And Refine Genetic Associations With Neurodegenerative Diseases, Yuriko Katsumata

Theses and Dissertations--Epidemiology and Biostatistics

Dementia is a clinical state caused by neurodegeneration and characterized by a loss of function in cognitive domains and behavior. Alzheimer’s disease (AD) is the most common form of dementia. Although the amyloid β (Aβ) protein and hyperphosphorylated tau aggregates in the brain are considered to be the key pathological hallmarks of AD, the exact cause of AD is yet to be identified. In addition, clinical diagnoses of AD can be error prone. Many previous studies have compared the clinical diagnosis of AD against the gold standard of autopsy confirmation and shown substantial AD misdiagnosis Hippocampal sclerosis of aging (HS-Aging) …

Informational Index And Its Applications In High Dimensional Data, Qingcong Yuan

Theses and Dissertations--Statistics

We introduce a new class of measures for testing independence between two random vectors, which uses expected difference of conditional and marginal characteristic functions. By choosing a particular weight function in the class, we propose a new index for measuring independence and study its property. Two empirical versions are developed, their properties, asymptotics, connection with existing measures and applications are discussed. Implementation and Monte Carlo results are also presented.

We propose a two-stage sufficient variable selections method based on the new index to deal with large p small n data. The method does not require model specification and especially focuses …

Family-Based Association Studies Of Autism In Boys Via Facial-Feature Clusters, Luke Andrew Settles

Masters Theses

"Autism spectrum disorder (ASD) refers to a set of developmental disorders with varied attributes. Due to its substantial heterogeneity in terms of behavioral and clinical phenotypes, it is challenging to discern the genetic biomarkers behind ASD, even though the disease is known to be genetic in nature. This serves as a motivation to detect relationships between single nucleotide polymorphisms (SNPs) and a causal autism disease susceptibility locus (DSL) within more homogeneous subgroups. Recently, clinically meaningful subclassifications of ASD have been discovered utilizing facial features of prepubescent boys. Therefore, through the employment of data from 44 prepubertal Caucasian boys with ASD …

Analysis Of Data From A Study To Identify Potential Biomarkers To Indicate Renal Injury, Mitchell D. Tahtinen

Dissertations, Master's Theses and Master's Reports

Ureteropelvic junction obstruction is a disease in which flow from the kidney to the bladder is obstructed for extended periods of time causing irreversible damage to the kidney. Current tests to detect kidney damage caused by obstruction are not effective until significant damage occurs. The purpose of this report is to identify a panel of biomarkers in urine to detect kidney damage earlier by analyzing data collected from a two-part study. Currently, two established urinary biomarkers to indicate kidney damage are NGAL and KIM-1. Biomarkers of interest in this study are CD13, CD10, and CD26. Results from the linear mixed …

The Generalized Monotone Incremental Forward Stagewise Method For Modeling Longitudinal, Clustered, And Overdispersed Count Data: Application Predicting Nuclear Bud And Micronuclei Frequencies, Rebecca Lehman

Theses and Dissertations

With the influx of high-dimensional data there is an immediate need for statistical methods that are able to handle situations when the number of predictors greatly exceeds the number of samples. One such area of growth is in examining how environmental exposures to toxins impact the body long term. The cytokinesis-block micronucleus assay can measure the genotoxic effect of exposure as a count outcome. To investigate potential biomarkers, high-throughput assays that assess gene expression and methylation have been developed. It is of interest to identify biomarkers or molecular features that are associated with elevated micronuclei (MN) or nuclear bud (Nbud) …

Longitudinal And Geographical Modeling Of Circular Data With An Application To Sudden Infant Death Syndrome, Xinyan Cai

Theses and Dissertations

The aim of this thesis is to study seasonality of death in U.S. infants who died from SIDS. We also propose to investigate secular trends and geographical patterns of seasonal patterns of mortality. The application of circular statistics is used to describe the seasonality of the month of death in infants who died from SIDS in 1990, 2000 and 2010. The secular trends of seasonal patterns of SIDS mortality are investigated using a circular linear regression model after adjusting for potential confounders. The geographical variation in seasonal patterns of SIDS mortality is explored from the U.S. map and quantified by …

Statistical Methods For Multivariate And Correlated Data, Xinling Xu

Theses and Dissertations

A commonly encountered data type in real life is count data, especially in selfreported behavioral studies. One issue of the self-reported count data is the inaccuracy. In the first part of the dissertation, we are going to address one specific type of inaccuracy in bivariate count data–heaping. Copula functions are used for the formulation of the bivariate distribution. Using copula functions for solving data inaccuracy problems is still a new area, which we are going to explore in this dissertation.

We also discuss the methods for variable selection when the explanatory variables are highly correlated. In particular, our method is …

Evaluation Of Goodness-Of-Fit Tests For The Cox Proportional Hazards Model With Time-Varying Covariates, Shanshan Hong

Theses and Dissertations

The proportional hazards (PH) model, proposed by Cox (1972), is one of the most popular survival models for analyzing time-to-event data. To use the PH model properly, one must examine whether the data satisfy the PH assumption. An alternative model should be suggested if the PH assumption is invalid. The main purpose of this thesis is to examine the performance of five existing methods for assessing the PH assumption. Through extensive simulations, the powers of five different existing methods are compared; these methods include the likelihood ratio test, the Schoenfeld residuals test, the scaled Schoenfeld residuals test, Lin et al. …

Marginal Structural Cox Model For Survival Data With Treatment-Confounder Feedback, Yanan Zhang

Theses and Dissertations

In an observational longitudinal study, there can be time-varying exposure/treatment and time-varying confounders. When the confounders affect the exposure and prior exposure also has an impact on levels of confounders, there is treatment confounder feedback. To admit estimation of unbiased causal effects, these conditions need to be hold, exchangeability, positivity, consistency. The traditional method of conditioning on potential confounders does not meet these 3 conditions. Therefore, parameter estimates from traditional Cox model are biased casual effect estimates when the treatment confounder feedback exists. The marginal structural Cox model can be used to address this issue. By calculating and including inverse …

Comparing The Structural Components Variance Estimator And U-Statistics Variance Estimator When Assessing The Difference Between Correlated Aucs With Finite Samples, Anna L. Bosse

Theses and Dissertations

Introduction: The structural components variance estimator proposed by DeLong et al. (1988) is a popular approach used when comparing two correlated AUCs. However, this variance estimator is biased and could be problematic with small sample sizes.

Methods: A U-statistics based variance estimator approach is presented and compared with the structural components variance estimator through a large-scale simulation study under different finite-sample size configurations.

Results: The U-statistics variance estimator was unbiased for the true variance of the difference between correlated AUCs regardless of the sample size and had lower RMSE than the structural components variance estimator, providing better type 1 error …

Weighted Quantile Sum Regression For Analyzing Correlated Predictors Acting Through A Mediation Pathway On A Biological Outcome, Bhanu M. Evani

Theses and Dissertations

Abstract

Weighted Quantile Sum Regression for Analyzing Correlated Predictors Acting Through a Mediation Pathway on a Biological Outcome

By

Bhanu M. Evani, Ph.D.

A thesis submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy at Virginia Commonwealth University.

Virginia Commonwealth University, 2017.

Major Director: Robert A. Perera, Asst. Professor, Department of Biostatistics

This work examines mediated effects of a set of correlated predictors using the recently developed Weighted Quantile Sum (WQS) regression method. Traditionally, mediation analysis has been conducted using the multiple regression method, first proposed by Baron and Kenny (1986), which has since …

Characterization Of Hiv Diversity, Phylodynamics And Drug Resistance In Washington, Dc., Marcos Pérez-Losada, Amanda D Castel, Brittany Lewis, Michael Kharfen, Charles P Cartwright, Bruce Huang, Taylor Maxwell, Alan E Greenberg, Keith A Crandall

Epidemiology Faculty Publications

No abstract provided.

Novel Models Of Visual Topographic Map Alignment In The Superior Colliculus., Ruben A Tikidji-Hamburyan, Tarek A El-Ghazawi, Jason W. Triplett

Pediatrics Faculty Publications

The establishment of precise neuronal connectivity during development is critical for sensing the external environment and informing appropriate behavioral responses. In the visual system, many connections are organized topographically, which preserves the spatial order of the visual scene. The superior colliculus (SC) is a midbrain nucleus that integrates visual inputs from the retina and primary visual cortex (V1) to regulate goal-directed eye movements. In the SC, topographically organized inputs from the retina and V1 must be aligned to facilitate integration. Previously, we showed that retinal input instructs the alignment of V1 inputs in the SC in a manner dependent on …

Improving Power In Group Sequential, Randomized Trials By Adjusting For Prognostic Baseline Variables And Short-Term Outcomes, Tianchen Qian, Michael Rosenblum, Huitong Qiu

Johns Hopkins University, Dept. of Biostatistics Working Papers

In group sequential designs, adjusting for baseline variables and short-term outcomes can lead to increased power and reduced sample size. We derive formulas for the precision gain from such variable adjustment using semiparametric estimators for the average treatment effect, and give new results on what conditions lead to substantial power gains and sample size reductions. The formulas reveal how the impact of prognostic variables on the precision gain is modified by the number of pipeline participants, analysis timing, enrollment rate, and treatment effect heterogeneity, when the semiparametric estimator uses correctly specified models. Given set prognostic value of baseline variables and …

Stochastic Optimization Of Adaptive Enrichment Designs For Two Subpopulations, Aaron Fisher, Michael Rosenblum

Johns Hopkins University, Dept. of Biostatistics Working Papers

An adaptive enrichment design is a randomized trial that allows enrollment criteria to be modified at interim analyses, based on a preset decision rule. When there is prior uncertainty regarding treatment effect heterogeneity, these trial designs can provide improved power for detecting treatment effects in subpopulations. We present a simulated annealing approach to search over the space of decision rules and other parameters for an adaptive enrichment design. The goal is to minimize the expected number enrolled or expected duration, while preserving the appropriate power and Type I error rate. We also explore the benefits of parallel computation in the …

An Examination Of The Neural Unreliability Thesis Of Autism, John Butler, Sophie Molholm, Gizely Andrade, John J. Foxe

Articles

An emerging neuropathological theory of Autism, referred to here as “the neural unreliability thesis,” proposes greater variability in moment-to-moment cortical representation of environmental events, such that the system shows general instability in its impulse response function. Leading evidence for this thesis derives from functional neuroimaging, a methodology ill-suited for detailed assessment of sensory transmission dynamics occurring at the millisecond scale. Electrophysiological assessments of this thesis, however, are sparse and unconvincing. We conducted detailed examination of visual and somatosensory evoked activity using high-density electrical mapping in individuals with autism (N = 20) and precisely matched neurotypical controls (N = 20), recording …

Very Rapid Onset Cannabis Dependence Risk In Relation To Co-Occurring Use Of Other Psychoactive Drugs, Olga A. Vsevolozhskaya, Fernando A. Wagner, James C. Anthony

Biostatistics Presentations

Background: Epidemiological estimates for lifetime cumulative incidence indicate that for every 9-11 who start using cannabis, one becomes a case of the cannabis dependence syndrome (CDS) – i.e., roughly 9%-11%. More recent estimates clarify that CDS risk might be much lower among ’cannabis only’ users, due in part to the fact that many ’cannabis only’ users try the drug a few times and never again. We turned to Hill functional analysis in order to study CDS probability soon after 1st cannabis use, estimated across strata defined by the number of recent days of cannabis use, with an acknowledgment that a …

Pertussis-Associated Pneumonia In Infants And Children From Low- And Middle-Income Countries Participating In The Perch Study., Breanna Barger-Kamate, Maria Deloria Knoll, E Wangeci Kagucia, Christine Prosperi, Henry C Baggett, Daniel E. Park, +31 Additional Authors

Epidemiology Faculty Publications

BACKGROUND:  Few data exist describing pertussis epidemiology among infants and children in low- and middle-income countries to guide preventive strategies.

METHODS:  Children 1-59 months of age hospitalized with World Health Organization-defined severe or very severe pneumonia in 7 African and Asian countries and similarly aged community controls were enrolled in the Pneumonia Etiology Research for Child Health study. They underwent a standardized clinical evaluation and provided nasopharyngeal and oropharyngeal swabs and induced sputum (cases only) for Bordetella pertussis polymerase chain reaction. Risk factors and pertussis-associated clinical findings were identified.

RESULTS:  Bordetella pertussis was detected in 53 of 4200 (1.3%) cases …

Analysis Of Hiv Diversity In Hiv-Infected Black Men Who Have Sex With Men (Hptn 061), Iris Chen, Gordon Chau, Jing Wang, William Clarke, Mark A. Marzinke, Manya Magnus, +14 Additional Authors

Epidemiology Faculty Publications

Background

HIV populations often diversify in response to selective pressures, such as the immune response and antiretroviral drug use. We analyzed HIV diversity in Black men who have sex with men who were enrolled in the HIV Prevention Trials Network 061 study.

Methods

A high resolution melting (HRM) diversity assay was used to measure diversity in six regions of the HIV genome: two in gag, one in pol, and three in env. HIV diversity was analyzed for 146 men who were HIV infected at study enrollment, including three with acute infection and 13 with recent infection (identified …

Genomics And Csf Analyses Implicate Thyroid Hormone In Hippocampal Sclerosis Of Aging, Peter T. Nelson, Yuriko Katsumata, Kwangsik Nho, Sergey C. Artiushin, Gregory A. Jicha, Wang-Xia Wang, Erin L. Abner, Andrew J. Saykin, Walter A. Kukull, Alzheimer’S Disease Neuroimaging Initiative (Adni), David W. Fardo

Sanders-Brown Center on Aging Faculty Publications

We report evidence of a novel pathogenetic mechanism in which thyroid hormone dysregulation contributes to dementia in elderly persons. Two single nucleotide polymorphisms (SNPs) on chromosome 12p12 were the initial foci of our study: rs704180 and rs73069071. These SNPs were identified by separate research groups as risk alleles for non-Alzheimer’s neurodegeneration. We found that the rs73069071 risk genotype was associated with hippocampal sclerosis (HS) pathology among people with the rs704180 risk genotype (National Alzheimer’s Coordinating Center/Alzheimer’s Disease Genetic Consortium data; n = 2113, including 241 autopsy-confirmed HS cases). Furthermore, both rs704180 and rs73069071 risk genotypes were associated with widespread brain …

Characterizing The Effects Of Repetitive Head Trauma In Female Soccer Athletes For Prevention Of Mild Traumatic Brain Injury, Diana Otero Svaldi

Open Access Dissertations

As participation in women’s soccer continues to grow and the longevity of female athletes’ careers continues to increase, prevention of mTBI in women’s soccer has become a major concern for female athletes as the long-term risks associated with a history of mTBI are well documented. Among women’s sports, soccer exhibits the highest concussion rates, on par with those of men’s football at the collegiate level. Head impact monitoring technology has revealed that “concussive hits” occurring directly before symptomatic injury are not predictive of mTBI, suggesting that the cumulative effect of repetitive head impacts experienced by collision sport athletes should be …

Self-Reported Sleep Apnea And Dementia Risk: Findings From The Prevention Of Alzheimer's Disease With Vitamin E And Selenium Trial, Xiuhua Ding, Richard J. Kryscio, Joshua Turner, Gregory A. Jicha, Gregory E. Cooper, Allison M. Caban-Holt, Frederick A. Schmitt, Erin L. Abner

Sanders-Brown Center on Aging Faculty Publications

OBJECTIVES: To investigate the association between baseline sleep apnea and risk of incident dementia in the Prevention of Alzheimer's Disease with Vitamin E and Selenium (PREADViSE) study and to explore whether the association depends on apolipoprotein E (APOE) ɛ4 allele status.

DESIGN: Secondary analysis based on data collected during PREADViSE.

SETTING: Participants were assessed at 128 local clinical study sites during the clinical trial phase and later were followed by telephone from a centralized location.

PARTICIPANTS: Men enrolled in PREADViSE (without dementia or other active neurological conditions that affect cognition such as major psychiatric disorders, including depression; N = …

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. …

Gathering Steam In Health Care: A Student History, Michael J. Leach

The Transdisciplinary STEAM+ Journal

In this reflection, I demonstrate STEAM in health care by outlining my 15 years as a university student engaged in formal education, extracurricular learning, research, and employment.

Efficiency Of Two Sample Tests Via The T-Mean Survival Time For Analyzing Event Time Observations, Lu Tian, Haoda Fu, Stephen J. Ruberg, Hajime Uno, Lj Wei

Harvard University Biostatistics Working Paper Series

In comparing two treatments with the event time observations, the hazard ratio (HR) estimate is routinely used to quantify the treatment difference. However, this model dependent estimate may be difficult to interpret clinically especially when the proportional hazards (PH) assumption is violated. An alternative estimation procedure for treatment efficacy based on the restricted means survival time or t-year mean survival time (t-MST) has been discussed extensively in the statistical and clinical literature. On the other hand, a statistical test 1 via the HR or its asymptotically equivalent counterpart, the logrank test, is asymptotically distribution-free. In this paper, we assess the …

Effectivity Of Foot Care Education Program In Improving Knowledge, Self-Efficacy And Foot Care Behavior Among Diabetes Mellitus Patients In Banjarbaru, Indonesia, Mahdalena Mahdalena, Endang Sri Purwanti Ningsih

Kesmas

Masalah kaki diabetik di Indonesia masih merupakan masalah besar dan masih memerlukan perhatian yang optimal. Edukasi perawatan kaki adalah salah satu upaya yang harus dilakukan dalam mencegah masalah kaki untuk pasien diabetes melitus. Penelitian ini bertujuan untuk menganalisis efektivitas program pendidikan perawatan kaki dalam meningkatkan pengetahuan, efikasi diri, dan perilaku perawatan kaki pasien diabetes di wilayah Banjarbaru. Jenis penelitian yang digunakan adalah quasi experimental dengan prepost test, dilakukan di puskesmas wilayah Banjarbaru tahun 2013. Kelompok intervensi diberikan program pendidikan perawatan kaki. Sampel berjumlah 48 pasien (32 orang kelompok intervensi dan 16 orang kelompok kontrol) menggunakan teknik purposive sampling. Variabel yang …

Lack Of Exclusive Breastfeeding Among Working Mothers In Indonesia, Yulia Sari

Kesmas

Keberlangsungan proses menyusui pada saat ibu kembali bekerja merupakan isu serius yang harus segera ditindaklanjuti agar program pemberian Air Susu Ibu (ASI) eksklusif selama enam bulan pertama kehidupan dapat tercapai. Selain memberikan banyak manfaat bagi bayi, ASI juga bermanfaat bagi ibu dan pengusaha. Penelitian ini bertujuan untuk mengetahui hubungan ibu bekerja terhadap pemberian ASI eksklusif. Desain penelitian yang digunakan adalah potong lintang dengan data sekunder Survei Demografi dan Kesehatan Indonesia (SDKI) tahun 2012 dengan sampel berjumlah 1.193 ibu berusia 15 – 49 tahun yang memiliki bayi berusia 0-5 bulan. Berdasarkan analisis multivariat, ibu bekerja dapat menurunkan peluang pemberian ASI eksklusif …

The Risk Of Pneumonia Among Toddlers In Lambatee, Aceh, Rapitos Sidiq, Ritawati Ritawati, Roma Sitio, Siti Hajar

Kesmas

Pneumonia merupakan salah satu masalah kesehatan global yang sangat penting pada anak bawah lima tahun (balita), khususnya pada negara-negara berkembang. Saat ini, pneumonia merupakan salah satu kasus penyebab kematian pada anak terbesar, terutama pada periode baru lahir. Di Provinsi Aceh, penyakit pneumonia merupakan penyakit urutan ke-8 dari 25 penyakit terbesar yang ditemukan di puskesmas dengan jumlah 1.112 kasus. Sedangkan besarnya kasus pneumonia pada penderita rawat jalan di Aceh mencapai 434 kasus (29,03%). Penelitian ini bertujuan untuk mengetahui faktor-faktor yang berhubungan dengan kejadian pneumonia pada balita. Penelitian bersifat analitik dengan desain potong lintang. Sampel penelitian adalah ibu dan balita yang berjumlah …