Biostatistics Commons^™

Statistical Estimation Of T1 Relaxation Time Using Conventional Magnetic Resonance Imaging, Amanda Mejia, Elizabeth M. Sweeney, Blake Dewey, Govind Nair, Pascal Sati, Colin Shea, Daniel S. Reich, Russell T. Shinohara

UPenn Biostatistics Working Papers

Quantitative T₁ maps estimate T₁ relaxation times and can be used to assess diffuse tissue abnormalities within normal-appearing tissue. T₁ maps are popular for studying the progression and treatment of multiple sclerosis (MS). However, their inclusion in standard imaging protocols remains limited due to the additional scanning time and expert calibration required and susceptibility to bias and noise. Here, we propose a new method of estimating T₁ maps using four conventional MR images, which are intensity- normalized using cerebellar gray matter as a reference tissue and related to T₁ using a smooth regression model. Using …

Confident Difference Criterion: A New Bayesian Differentially Expressed Gene Selection Algorithm With Applications., Fang Yu, Ming-Hui Chen, Lynn Kuo, Heather Talbott, John S. Davis

Journal Articles: Biostatistics

BACKGROUND: Recently, the Bayesian method becomes more popular for analyzing high dimensional gene expression data as it allows us to borrow information across different genes and provides powerful estimators for evaluating gene expression levels. It is crucial to develop a simple but efficient gene selection algorithm for detecting differentially expressed (DE) genes based on the Bayesian estimators.

RESULTS: In this paper, by extending the two-criterion idea of Chen et al. (Chen M-H, Ibrahim JG, Chi Y-Y. A new class of mixture models for differential gene expression in DNA microarray data. J Stat Plan Inference. 2008;138:387-404), we propose two new gene …

C-Learning: A New Classification Framework To Estimate Optimal Dynamic Treatment Regimes, Baqun Zhang, Min Zhang

The University of Michigan Department of Biostatistics Working Paper Series

Personalizing treatment to accommodate patient heterogeneity and the evolving nature of a disease over time has received considerable attention lately. A dynamic treatment regime is a set of decision rules, each corresponding to a decision point, that determine that next treatment based on each individual’s own available characteristics and treatment history up to that point. We show that identifying the optimal dynamic treatment regime can be recast as a sequential classification problem and is equivalent to sequentially minimizing a weighted expected misclassification error. This general classification perspective targets the exact goal of optimally individualizing treatments and is new and fundamentally …

On Simple Relations Between Difference-In-Differences And Negative Outcome Control Of Unobserved Confounding, Tamar Sofer, David B. Richardson, Elena Colincino, Joel Schwartz, Eric J. Tchetgen Tchetgen

Harvard University Biostatistics Working Paper Series

No abstract provided.

Lepski's Method And Adaptive Estimation Of Nonlinear Integral Functionals Of Density, Rajarshi Mukherjee, Eric J. Tchetgen Tchetgen, James M. Robins

Harvard University Biostatistics Working Paper Series

No abstract provided.

Extended Followup Of A Cohort Of Chromium Production Workers, Herman Jones Gibb, Peter St. John Lees, Jing Wang, Keri O'Leary

Epidemiology Faculty Publications

Background

The current study evaluates the mortality of 2,354 workers first employed at a Baltimore chromate production plant between 1950 and 1974.

Methods

The National Death Index (NDI Plus) was used to determine vital status and cause of death. Cumulative chromium (VI) exposure and nasal and skin irritation were evaluated as risk factors for lung cancer mortality.

Results

There are 91,186 person-years of observation and 217 lung cancer deaths. Cumulative chromium (VI) exposure, nasal irritation, nasal perforation, nasal ulceration, and other forms of irritation (e.g., skin irritation) were associated with lung cancer mortality.

Conclusion

Cumulative chromium (VI) exposure was a …

Sexual Networks And Hiv Risk Among Black Men Who Have Sex With Men In 6 U.S. Cities, Hong-Van Tieu, Ting-Yuan Liu, Sophia Hussen, Matthew Connor, Lei Wang, Gregory Phillips Ii, + 11 More

Epidemiology Faculty Publications

Background

Sexual networks may place U.S. Black men who have sex with men (MSM) at increased HIV risk.

Methods

Self-reported egocentric sexual network data from the prior six months were collected from 1,349 community-recruited Black MSM in HPTN 061, a multi-component HIV prevention intervention feasibility study. Sexual network composition, size, and density (extent to which members are having sex with one another) were compared by self-reported HIV serostatus and age of the men. GEE models assessed network and other factors associated with having a Black sex partner, having a partner with at least two age category difference (age difference between …

Germline Mutation Detection In Next Generation Sequencing Data And Tp53 Mutation Carrier Probability Estimation For Li-Fraumeni Syndrome, Gang Peng

Dissertations and Theses (Open Access)

Next generation sequencing technology has been widely used in genomic analysis, but its application has been compromised by the missing true variants, especially when these variants are rare. We proposed a family-based variant calling method, FamSeq, integrating Mendelian transmission information with de novo mutation and sequencing data to improve the variant calling accuracy. We investigated the factors impacting the improvement of family-based variant calling in simulation data and validated it in real sequencing data. In both simulation and real data, FamSeq works better than the single individual based method.

In FamSeq, we implemented four different methods for the Mendelian genetic …

Computerizing Efficient Estimation Of A Pathwise Differentiable Target Parameter, Mark J. Van Der Laan, Marco Carone, Alexander R. Luedtke

U.C. Berkeley Division of Biostatistics Working Paper Series

Frangakis et al. (2015) proposed a numerical method for computing the efficient influence function of a parameter in a nonparametric model at a specified distribution and observation (provided such an influence function exists). Their approach is based on the assumption that the efficient influence function is given by the directional derivative of the target parameter mapping in the direction of a perturbation of the data distribution defined as the convex line from the data distribution to a pointmass at the observation. In our discussion paper Luedtke et al. (2015) we propose a regularization of this procedure and establish the validity …

Caffeine Consumption Contributes To Skin Intrinsic Fluorescence In Type 1 Diabetes., Karen M Eny, Trevor J Orchard, Rachel Grace Miller, John Maynard, Denis M Grant, Tina Costacou, Patricia A. Cleary, Barbara H Braffett, Andrew D Paterson, Dcct/Edic Research Group

GW Biostatistics Center

Background: A variant (rs1495741) in the gene for the N-acetyltransferase 2 (NAT2) protein is associated with skin intrinsic fluorescence (SIF), a noninvasive measure of advanced glycation end products and other fluorophores in the skin. Because NAT2 is involved in caffeine metabolism, we aimed to determine whether caffeine consumption is associated with SIF and whether rs1495741 is associated with SIF independently of caffeine.

Materials and Methods: SIF was measured in 1,181 participants with type 1 diabetes from the Epidemiology of Diabetes Interventions and Complications study. Two measures of SIF were used: SIF1, using a 375-nm excitation light-emitting diode (LED), and …

Drawing Valid Targeted Inference When Covariate-Adjusted Response-Adaptive Rct Meets Data-Adaptive Loss-Based Estimation, With An Application To The Lasso, Wenjing Zheng, Antoine Chambaz, Mark J. Van Der Laan

U.C. Berkeley Division of Biostatistics Working Paper Series

Adaptive clinical trial design methods have garnered growing attention in the recent years, in large part due to their greater flexibility over their traditional counterparts. One such design is the so-called covariate-adjusted, response-adaptive (CARA) randomized controlled trial (RCT). In a CARA RCT, the treatment randomization schemes are allowed to depend on the patient’s pre-treatment covariates, and the investigators have the opportunity to adjust these schemes during the course of the trial based on accruing information (including previous responses), in order to meet a pre-specified optimality criterion, while preserving the validity of the trial in learning its primary study parameter.

In …

Negative Outcome Control For Unobserved Confounding Under A Cox Proportional Hazards Model, Eric J. Tchetgen Tchetgen, Tamar Sofer, David Richardson

Harvard University Biostatistics Working Paper Series

No abstract provided.

Survival Analysis With Functions Of Mis-Measured Covariate Histories: The Case Of Chronic Air Pollution Exposure In Relation To Mortality In The Nurses' Health Study, Xiaomei Liao, Molin Wang, Jaime E. Hart, Francine Laden, Donna Spiegelman

Harvard University Biostatistics Working Paper Series

Environmental epidemiologists are often interested in estimating the effect of functions of time-varying exposure histories, such as the 12-month moving average, in relation to chronic disease incidence or mortality. The individual exposure measurements that comprise such an exposure history are usually mis-measured, at least moderately, and, often, more substantially. To obtain unbiased estimates of Cox model hazard ratios for these complex mis-measured exposure functions, an extended risk set regression calibration (RRC) method for Cox models is developed and applied to a study of long-term exposure to the fine particulate matter ($PM_{2.5}$) component of air pollution in relation to all-cause mortality …

Nitrate And Nitrite Ingestion And Risk Of Ovarian Cancer Among Postmenopausal Women In Iowa, Maki Inoue-Choi, Rena R. Jones, Kristin E. Anderson, Kenneth P. Cantor, James R. Cerhan, Stuart Krasner, Kimberly Robien, Peter J. Weyer, Mary H. Ward

Epidemiology Faculty Publications

Nitrate and nitrite are precursors in the endogenous formation of N-nitroso compounds (NOC), potential human carcinogens. We evaluated the association of nitrate and nitrite ingestion with postmenopausal ovarian cancer risk in the Iowa Women's Health Study. Among 28,555 postmenopausal women, we identified 315 incident epithelial ovarian cancers from 1986 to 2010. Dietary nitrate and nitrite intakes were assessed at baseline using food frequency questionnaire data. Drinking water source at home was obtained in a 1989 follow-up survey. Nitrate-nitrogen (NO₃-N) and total trihalomethane (TTHM) levels for Iowa public water utilities were linked to residences and average levels were …

Fast, Accurate, And Reliable Molecular Docking With Quickvina 2, Amr Alhossary, Stephanus Daniel Handoko, Yuguang Mu, Chee-Keong Kwoh

Research Collection School Of Computing and Information Systems

Motivation: The need for efficient molecular docking tools for high-throughput screening is growing alongside the rapid growth of drug-fragment databases. AutoDock Vina ('Vina') is a widely used docking tool with parallelization for speed. QuickVina ('QVina 1') then further enhanced the speed via a heuristics, requiring high exhaustiveness. With low exhaustiveness, its accuracy was compromised. We present in this article the latest version of QuickVina ('QVina 2') that inherits both the speed of QVina 1 and the reliability of the original Vina.Results: We tested the efficacy of QVina 2 on the core set of PDBbind 2014. With the default exhaustiveness level …

Size And Power Of Tests Of Hypotheses On Survival Parameters From The Lindley Distribution With Covariates, Macaulay Okwuokenye, Karl E. Peace

Biostatistics: Faculty Publications

The Lindley model is considered as an alternative model facilitating analyses of time-to-event data with covariates. Covariate information is incorporated using the Cox’s proportional hazard model with the Lindley model at the timedependent component. Simulation studies are performed to assess the size and power of tests of hypotheses on parameters arising from maximum likelihood estimators of parameters in the Lindley model. Results are contrasted with that arising from Cox’s partial maximum likelihood estimator. The Linley model is used to analyze a publicly available data set and contrasted with other models.

Joint Modeling Of Treatment Effect On Time-To-Event Endpoint And Safety Covariates In Control Clinical Trial Data Analysis, Kao-Tai Tsai, Karl E. Peace

Biostatistics: Faculty Publications

It is a common practice to perform a separate analysis of efficacy and safety data from clinical trials to estimate the benefit and risk aspects of a particular treatment regimen. However, by doing so, one is likely to miss the complete picture of the treatment effect given that these data are generated from the same study subjects and therefore most likely will be correlated. Therefore, it is desirable to analyze these data jointly to obtain a more complete profile of the treatment regimen. A substantial number of statistical methodologies have been proposed in the last decade to model the time-to-event …

Doubly Robust Estimation Of A Marginal Average Effect Of Treatment On The Treated With An Instrumental Variable, Lan Liu, Wang Miao, Baoluo Sun, James M. Robins, Eric J. Tchetgen Tchetgen

Harvard University Biostatistics Working Paper Series

No abstract provided.

One-Step Targeted Minimum Loss-Based Estimation Based On Universal Least Favorable One-Dimensional Submodels, Mark J. Van Der Laan

U.C. Berkeley Division of Biostatistics Working Paper Series

Consider a study in which one observes n independent and identically distributed random variables whose probability distribution is known to be an element of a particular statistical model, and one is concerned with estimation of a particular real valued pathwise differentiable target parameter of this data probability distribution. The canonical gradient of the pathwise derivative of the target parameter, also called the efficient influence curve, defines an asymptotically efficient estimator as an estimator that is asymptotically linear with influence curve equal to the efficient influence curve.The targeted maximum likelihood estimator is a two stage estimator obtained by constructing a so …

Identification And Doubly Robust Estimation Of Data Missing Not At Random With An Ancillary Variable, Wang Miao, Eric Tchetgen Tchetgen, Zhi Geng

Harvard University Biostatistics Working Paper Series

No abstract provided.