Biostatistics Commons^™

Statistical Methods For Two Problems In Cancer Research: Analysis Of Rna-Seq Data From Archival Samples And Characterization Of Onset Of Multiple Primary Cancers, Jialu Li

Dissertations and Theses (Open Access)

My dissertation is focused on quantitative methodology development and application for two important topics in translational and clinical cancer research.

The first topic was motivated by the challenge of applying transcriptome sequencing (RNA-seq) to formalin-fixation and paraffin-embedding (FFPE) tumor samples for reliable diagnostic development. We designed a biospecimen study to directly compare gene expression results from different protocols to prepare libraries for RNA-seq from human breast cancer tissues, with randomization to fresh-frozen (FF) or FFPE conditions. To comprehensively evaluate the FFPE RNA-seq data quality for expression profiling, we developed multiple computational methods for assessment, such as the uniformity and continuity …

Comparison Of Survival Curves Between Cox Proportional Hazards, Random Forests, And Conditional Inference Forests In Survival Analysis, Brandon Weathers

All Graduate Plan B and other Reports, Spring 1920 to Spring 2023

Survival analysis methods are a mainstay of the biomedical fields but are finding increasing use in other disciplines including finance and engineering. A widely used tool in survival analysis is the Cox proportional hazards regression model. For this model, all the predicted survivor curves have the same basic shape, which may not be a good approximation to reality. In contrast the Random Survival Forests does not make the proportional hazards assumption and has the flexibility to model survivor curves that are of quite different shapes for different groups of subjects. We applied both techniques to a number of publicly available …

Functional Human Grin2b Promoter Polymorphism And Variation Of Mental Processing Speed In Older Adults, Yang Jiang, Ming Kuan Lin, Gregory A. Jicha, Xiuhua Ding, Sabrina L. Mcilwrath, David W. Fardo, Lucas S. Broster, Frederick A. Schmitt, Richard J. Kryscio, Robert H. Lipsky

Behavioral Science Faculty Publications

We investigated the role of a single nucleotide polymorphism rs3764030 (G > A) within the human GRIN2B promoter in mental processing speed in healthy, cognitively intact, older adults. In vitro DNA-binding and reporter gene assays of different allele combinations in transfected cells showed that the A allele was a gain-of-function variant associated with increasing GRIN2B mRNA levels. We tested the hypothesis that individuals with A allele will have better memory performance (i.e. faster reaction times) in older age. Twenty-eight older adults (ages 65-86) from a well-characterized longitudinal cohort were recruited and performed a modified delayed match-to-sample task. The rs3764030 polymorphism was …

Estimating Autoantibody Signatures To Detect Autoimmune Disease Patient Subsets, Zhenke Wu, Livia Casciola-Rosen, Ami A. Shah, Antony Rosen, Scott L. Zeger

Johns Hopkins University, Dept. of Biostatistics Working Papers

Autoimmune diseases are characterized by highly specific immune responses against molecules in self-tissues. Different autoimmune diseases are characterized by distinct immune responses, making autoantibodies useful for diagnosis and prediction. In many diseases, the targets of autoantibodies are incompletely defined. Although the technologies for autoantibody discovery have advanced dramatically over the past decade, each of these techniques generates hundreds of possibilities, which are onerous and expensive to validate. We set out to establish a method to greatly simplify autoantibody discovery, using a pre-filtering step to define subgroups with similar specificities based on migration of labeled, immunoprecipitated proteins on sodium dodecyl sulfate …

Network Exploration Of Correlated Multivariate Protein Data For Alzheimer's Disease Association, Matthew J. Lane

Theses

Alzheimer Disease (AD) is difficult to diagnose by using genetic testing or other traditional methods. Unlike diseases with simple genetic risk components, there exists no single marker determining as to whether someone will develop AD. Furthermore, AD is highly heterogeneous and different subgroups of individuals develop the disease due to differing factors. Traditional diagnostic methods using perceivable cognitive deficiencies are often too little too late due to the brain having suffered damage from decades of disease progression. In order to observe AD at early stages prior to the observation of cognitive deficiencies, biomarkers with greater accuracy are required. By using …

Positive Affect Predicts Cerebral Glucose Metabolism In Late Middle-Aged Adults., Christopher Nicholas, Siobhan M Hoscheidt, Lindsay R Clark, Annie M Racine, Sara E Berman, Rebecca L Koscik, N Maritza Dowling, Sanjay Asthana, Bradley T Christian, Mark A Sager, Sterling C Johnson

GW Biostatistics Center

Positive affect is associated with a number of health benefits; however, few studies have examined the relationship between positive affect and cerebral glucose metabolism, a key energy source for neuronal function and a possible index of brain health. We sought to determine if positive affect was associated with cerebral glucose metabolism in late middle-aged adults (n = 133). Participants completed the positive affect subscale of the Center for Epidemiological Studies Depression Scale at two time points over a two-year period and underwent 18F-fluorodeoxyglucose-positron emission tomography scanning. After controlling for age, sex, perceived health status, depressive symptoms, anti-depressant use, family …

Identification Of Prognostic Genes And Gene Sets For Early-Stage Non-Small Cell Lung Cancer Using Bi-Level Selection Methods, Suyan Tian, Chi Wang, Howard H. Chang, Jianguo Sun

Biostatistics Faculty Publications

In contrast to feature selection and gene set analysis, bi-level selection is a process of selecting not only important gene sets but also important genes within those gene sets. Depending on the order of selections, a bi-level selection method can be classified into three categories – forward selection, which first selects relevant gene sets followed by the selection of relevant individual genes; backward selection which takes the reversed order; and simultaneous selection, which performs the two tasks simultaneously usually with the aids of a penalized regression model. To test the existence of subtype-specific prognostic genes for non-small cell lung cancer …

Outcomes After Diagnosis Of Mild Cognitive Impairment In A Large Autopsy Series, Erin L. Abner, Richard J. Kryscio, Frederick A. Schmitt, David W. Fardo, Daniela C. Moga, Eseosa T. Ighodaro, Gregory A. Jicha, Lei Yu, Hiroko H. Dodge, Chengjie Xiong, Randall L. Woltjer, Julie A. Schneider, Nigel J. Cairns, David A. Bennett, Peter T. Nelson

Epidemiology and Environmental Health Faculty Publications

OBJECTIVE: To determine clinical and neuropathological outcomes following a clinical diagnosis of mild cognitive impairment (MCI).

METHODS: Data were drawn from a large autopsy series (N = 1,337) of individuals followed longitudinally from normal or MCI status to death, derived from 4 Alzheimer Disease (AD) Centers in the United States.

RESULTS: Mean follow‐up was 7.9 years. Of the 874 individuals ever diagnosed with MCI, final clinical diagnoses were varied: 39.2% died with an MCI diagnosis, 46.8% with a dementia diagnosis, and 13.9% with a diagnosis of intact cognition. The latter group had pathological features resembling those with a final clinical …

Level Of Patient-Physician Agreement In Assessment Of Change Following Conservative Rehabilitation For Shoulder Pain, Stephanie D. Moore-Reed, W. Ben Kibler, Heather M. Bush, Timothy L. Uhl

Biostatistics Faculty Publications

Background Assessment of health-related status has been shown to vary between patients and physicians, although the degree of patient–physician discordance in the assessment of the change in status is unknown.

Methods Ninety-nine patients with shoulder dysfunction underwent a standardized physician examination and completed several self-reported questionnaires. All patients were prescribed the same physical therapy intervention. Six weeks later, the patients returned to the physician, when self-report questionnaires were re-assessed and the Global Rating of Change (GROC) was completed by the patient. The physician completed the GROC retrospectively. To determine agreement between patient and physician, intra-class correlation (ICC) coefficient and Pearson’s …

Pre-Pregnancy Body Mass Index Is Associated With Dietary Inflammatory Index And C-Reactive Protein Concentrations During Pregnancy, Dayeon Shin, Junguk Hur, Eun-Hee Cho, Hae-Kyung Chung, Nitin Shivappa, Michael D. Wirth, James R. Hébert, Kyung Won Lee

Faculty Publications

There have been a limited number of studies examining the association between pre-pregnancy body mass index (BMI) and dietary inflammation during pregnancy. Our aim is to examine the association between pre-pregnancy BMI and the Dietary Inflammatory Index (DII)™ and C-reactive protein (CRP) concentrations during pregnancy. The study included 631 pregnant American women from the National Health and Nutrition Examination Survey (NHANES) cross-sectional examinations from 2003 to 2012. Pre-pregnancy BMI was calculated based on self-reported pre-pregnancy weight and measured height. The cut-offs of <18.5 (underweight), 18.5–24.9 (normal), 25.0–29.9 (overweight), and ≥30 kg/m2 (obese) were used to categorize the weight status of pregnant women prior to pregnancy. The DII, a literature-based dietary index to assess the inflammatory properties of diet, was estimated based on a one-day 24-h recall. Multivariable linear and logistic regressions were performed to estimate beta coefficients and the adjusted odds ratios (AORs) and 95% confidence intervals (95% CIs) on the association of pre-pregnancy BMI categories with the DII and CRP concentrations during pregnancy. After controlling for variables including: race/ethnicity, family poverty income ratio, education, marital status, month in pregnancy, and smoking status during pregnancy; women who were obese before pregnancy (n = 136) had increased odds for being in the highest tertile of the DII and CRP concentrations compared to women with normal weight (AORs 2.40, 95% CIs 1.01–5.71; AORs 24.84, 95% CIs 6.19–99.67, respectively). These findings suggest that women with pre-pregnancy obesity had greater odds of reporting higher DII and having elevated CRP. In conclusion, high pre-pregnancy BMI was associated with increased odds of pro-inflammatory diet and elevated CRP levels during pregnancy in the USA.

Examining The Prevalence Rates Of Preexisting Maternal Medical Conditions And Pregnancy Complications By Source: Evidence To Inform Maternal And Child Research, Candace A. Robledo, Edwina H. Yeung, Pauline Mendola, Rajeshwari Sundaram, Nansi S. Boghossian, Erin M. Bell, Charlotte Druschel

School of Medicine Publications

Objectives—We sought to examine whether there are systematic differences in ascertainment of preexisting maternal medical conditions and pregnancy complications from three common data sources used in epidemiologic research

Methods—Diabetes mellitus, chronic hypertension, gestational diabetes mellitus (GDM), gestational hypertensive disorders (GHD), placental abruption and premature rupture of membranes (PROM) among 4821 pregnancies were identified via birth certificates, maternal self-report at approximately 4 months postpartum and by discharge codes from the Statewide Planning and Research Cooperative System (SPARCS), a mandatory New York State hospital reporting system. The kappa statistic (k) was estimated to ascertain beyond chance agreement of outcomes between birth certificates …

Contributions To Statistical Testing, Prediction, And Modeling, John C. Pesko

Mathematics & Statistics ETDs

1. "Parametric Bootstrap (PB) and Objective Bayesian (OB) Testing with Applications to Heteroscedastic ANOVA": For one-way heteroscedastic ANOVA, we show a close relationship between the PB and OB approaches to significance testing, demonstrating the conditions for which the two approaches are equivalent. Using a simulation study, PB and OB performance is compared to a test based on the predictive distribution as well as the unweighted test of Akritas & Papadatos (2004). We extend this work to the RCBD with subsampling model, and prove a repeated sampling property and large sample property for general OB significance testing.

2. "Early Identification of …

Using The Roc Curve To Measure Association And Evaluate Prediction Accuracy For A Binary Outcome, Jingjing Yin, Robert L. Vogel

Biostatistics: Faculty Publications

This review article addresses the ROC curve and its advantage over the odds ratio to measure the association between a continuous variable and a binary outcome. A simple parametric model under the normality assumption and the method of Box-Cox transformation for non-normal data are discussed. Applications of the binormal model and the Box-Cox transformation under both univariate and multivariate inference are illustrated by a comprehensive data analysis tutorial. Finally, a summary and recommendations are given as to the usage of the binormal ROC curve.

A Statistical Method For The Conservative Adjustment Of False Discovery Rate (Q-Value)., Yinglei Lai

Epidemiology Faculty Publications

BACKGROUND: q-value is a widely used statistical method for estimating false discovery rate (FDR), which is a conventional significance measure in the analysis of genome-wide expression data. q-value is a random variable and it may underestimate FDR in practice. An underestimated FDR can lead to unexpected false discoveries in the follow-up validation experiments. This issue has not been well addressed in literature, especially in the situation when the permutation procedure is necessary for p-value calculation.

RESULTS: We proposed a statistical method for the conservative adjustment of q-value. In practice, it is usually necessary to calculate p-value by a permutation procedure. …

A Statistical Method For The Conservative Adjustment Of False Discovery Rate (Q-Value), Yinglei Lai

Epidemiology Faculty Publications

Background

q-value is a widely used statistical method for estimating false discovery rate (FDR), which is a conventional significance measure in the analysis of genome-wide expression data. q-value is a random variable and it may underestimate FDR in practice. An underestimated FDR can lead to unexpected false discoveries in the follow-up validation experiments. This issue has not been well addressed in literature, especially in the situation when the permutation procedure is necessary for p-value calculation.

Results

We proposed a statistical method for the conservative adjustment of q-value. In practice, it is usually necessary to calculate p …

Using A Respiratory Navigator Significantly Reduces Variability When Quantifying Left Ventricular Torsion With Cardiovascular Magnetic Resonance, Sean M. Hamlet, Christopher M. Haggerty, Jonathan D. Suever, Gregory J. Wehner, Kristin N. Andres, David K. Powell, Richard J. Charnigo, Brandon K. Fornwalt

Electrical and Computer Engineering Faculty Publications

Background: Left ventricular (LV) torsion is an important indicator of cardiac function that is limited by high inter-test variability (50% of the mean value). We hypothesized that this high inter-test variability is partly due to inconsistent breath-hold positions during serial image acquisitions, which could be significantly improved by using a respiratory navigator for cardiovascular magnetic resonance (CMR) based quantification of LV torsion.

Methods: We assessed respiratory-related variability in measured LV torsion with two distinct experimental protocols. First, 17 volunteers were recruited for CMR with cine displacement encoding with stimulated echoes (DENSE) in which a respiratory navigator was used to measure …

Using Ranked Auxiliary Covariate As A More Efficient Sampling Design For Ancova Model: Analysis Of A Psychological Intervention To Buttress Resilience, Rajai Jabrah, Hani Samawi, Robert Vogel, Haresh Rochani, Daniel Linder

Biostatistics: Faculty Publications

Drawing a sample can be costly or time consuming in some studies. However, it may be possible to rank the sampling units according to some baseline auxiliary covariates, which are easily obtainable, and/or cost efficient. Ranked set sampling (RSS) is a method to achieve this goal. In this paper, we propose a modified approach of the RSS method to allocate units into an experimental study that compares L groups. Computer simulation estimates the empirical nominal values and the empirical power values for the test procedure of comparing L different groups using modified RSS based on the regression approach in analysis …

The Impact Of National Health Insurance Policy To The Implementation Of Health Promotion Program On Public Health Center In Indonesia, Mochamad Iqbal Nurmansyah, Bulent Kilic

Kesmas

Jaminan Kesehatan Nasional (JKN) telah diimplementasikan di Indonesia pada 1 Januari 2014. Hal tersebut membawa beberapa perubahan pada aspek manajerial pada pusat kesehatan masyarakat (puskesmas). Penelitian ini bertujuan untuk mengidentifikasi dampak dari kebijakan JKN terhadap implementasi program promosi kesehatan di puskesmas di Kota Tangerang Selatan, Indonesia. Penelitian menggunakan metode kualitatif. Data dikumpulkan pada Februari – Maret 2016. Dampak program dilihat dalam hal kebijakan, pendanaan, fasilitas, sumber daya manusia dan pelaksanaan program promosi kesehatan. Dengan menggunakan metode purposive sampling, enam pengambil kebijakan, delapan pemberi layanan dan delapan penerima layanan diambil sebagai informan dalam penelitian ini. Pada analisis dokumen, 17 dokumen telah …

Effect Of School Community Empowerment Model Towards Handwashing Implementation Among Elementary School Students In Dayeuhkolot Subdistrict, Tetti Solehati, Cecep Eli Kosasih, Sri Susilawati, Mamat Lukman, Sayu Putu Yuni Paryati

Kesmas

Perilaku mencuci tangan dengan sabun di Indonesia masih menjadi masalah. Penyebabnya dikaitkan dengan kurangnya kesadaran dalam mencuci tangan pakai sabun. Penelitian ini bertujuan untuk mengetahui pengaruh pemberdayaan komunitas sekolah terhadap penerapan mencuci tangan di kalangan siswa sekolah dasar di Kecamatan Dayeuhkolot, Kabupaten Bandung. Penelitian ini menggunakan desain quasi eksperimental dengan pretest dan posttest serta melakukan analisis deskriptif dan inferensial. Sampel terdiri dari 24 guru, 377 siswa di kelas 4-6, dan 24 dokter kecil. Metode pendekatan dalam penelitian ini menggunakan usaha kesehatan sekolah terpadu (gabungan model fit for school dan UKS terpilih), yang terdiri dari enam tahap. Instrumen terdiri dari kuesioner …

Acceptance Of Medical Resume Completion At Dr. Radjiman Wediodiningrat Lawang Psychiatric Hospital, Silvia Shinta Devi, Aryo Dewanto, Lukman Hakim

Kesmas

Sistem kesehatan di Indonesia mengalami perubahan besar dengan diberlakukannya program Asuransi Kesehatan Nasional. Resume medis memiliki peran penting dalam klaim asuransi kesehatan, sehingga resume medis yang terlambat dan tidak lengkap akan mengganggu proses klaim asuransi. Penelitian ini bertujuan untuk mengetahui pengaruh persepsi kemudahan penggunaan, persepsi manfaat, dan sikap pada penerimaan dokter dalam menyelesaikan resume medis. di Dr Radjiman Wedyodiningrat Psychiatric Hospital Lawang berdasarkan Technology Acceptance Model. Technology Acceptance Model digunakan sebagai model dalam penelitian ini karena resume medis merupakan salah satu bentuk teknologi informasi yang masih dilakukan secara manual. Pengumpulan data untuk penelitian ini dilakukan pada bulan Maret 2016 dengan …