Physical Sciences and Mathematics Commons^™

Estimating Effects With Rare Outcomes And High Dimensional Covariates: Knowledge Is Power, Laura Balzer, J. Ahern, S. Galea, M. Van Der Laan

Laura B. Balzer

Targeted Estimation Of Marginal Absolute And Relative Associations In Case-Control Data: An Application In Social Epidemiology, M. Pearl, Laura Balzer, J. Ahern

Laura B. Balzer

Introduction To Targeted Learning, Laura Balzer

Laura B. Balzer

No abstract provided.

Early Diagnosis Of Dengue Disease Severity In A Resource-Limited Asian Country, Philippe Cavailler, Arnaud Tarantola, Yee Sin Leo, Andrew A. Lover, Anne Rachline, Duch Moniboth, Rekol Huy, Ai Li Quake, Kdan Yuvatha, Veasna Duong, Jeremy L. Brett, Philippe Buchy

Andrew Lover

Serological Evidence For Localized And Persistent Antibody Response In Zika Virus-Positive Neonates With Microcephaly (Brazil, 2015)- A Secondary Analysis, Andrew A. Lover

Andrew Lover

Corn-Soybean And Alternative Cropping Systems Effects On No 3 -N Leaching Losses In Subsurface Drainage Water, Rameshwar S. Kanwar, Richard M. Cruse, Mohammadreza Ghaffarzadeh, Allah Bakhsh, Douglas Karlen, Theodore B. Bailey

Douglas L Karlen

Alternative cropping systems can improve resource use efficiency, increase corn grain yield, and help in reducing negative impacts on the environment. A 6-yr (1993 to 1998) field study was conducted at the Iowa State University’s Northeastern Research Center near Nashua, Iowa, to evaluate the effects of non-traditional cropping systems [strip inter cropping (STR)-corn (Zea mays L.)/soybean (Glycine max L.)/oats (Avina sativa L.)]; alfalfa rotation (ROT)-3-yr (1993 to 1995) alfalfa (Medicago sativa L.) followed by corn in 1996, soybean in 1997, and oats in 1998), and traditional cropping system (corn after soybean (CS) and soybean after corn (SC) on the flow …

Cropping System Effects On No3-N Loss With Subsurface Drainage Water, Allah Bakhsh, Rameshwar S. Kanwar, Theodore B. Bailey, Cynthia A. Cambardella, Douglas Karlen, Thomas S. Colvin

Douglas L Karlen

An appropriate combination of tillage and nitrogen management practices will be necessary to develop sustainable farming practices. A six–year (1993–1998) field study was conducted on subsurface–drained Clyde–Kenyon–Floyd soils to quantify the impact of two tillage systems (chisel plow vs. no tillage) and two N fertilizer management practices (preplant single application vs. late–spring soil test based application) on nitrate–nitrogen (NO3–N) leaching loss with subsurface drain discharge from corn (Zea mays L.) soybean (Glycine max L.) rotation plots. Preplant injected urea ammonium nitrate solution (UAN) fertilizer was applied at the rate of 110 kg ha–1 to chisel plow and no–till corn plots, …

Flexible Penalized Regression For Functional Data...And Other Complex Data Objects, Philip T. Reiss

Philip T. Reiss

No abstract provided.

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

Alex Luedtke

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 …

Set-Based Tests For Genetic Association In Longitudinal Studies, Zihuai He, Min Zhang, Seunggeun Lee, Jennifer A. Smith, Xiuqing Guo, Walter Palmas, Sharon L.R. Kardia, Ana V. Diez Roux, Bhramar Mukherjee

Jennifer McMahon

Genetic association studies with longitudinal markers of chronic diseases (e.g., blood pressure, body mass index) provide a valuable opportunity to explore how genetic variants affect traits over time by utilizing the full trajectory of longitudinal outcomes. Since these traits are likely influenced by the joint eff#11;ect of multiple variants in a gene, a joint analysis of these variants considering linkage disequilibrium (LD) may help to explain additional phenotypic variation. In this article, we propose a longitudinal genetic random field model (LGRF), to test the association between a phenotype measured repeatedly during the course of an observational study and a set …

A Latent Variable Transformation Model Approach For Exploring Dysphagia, Anna Snavely, David P. Harrington, Yi Li

David E. Harrington

No abstract provided.

Wavelet-Domain Regression And Predictive Inference In Psychiatric Neuroimaging, Philip T. Reiss, Lan Huo, Yihong Zhao, Clare Kelly, R. Todd Ogden

Philip T. Reiss

An increasingly important goal of psychiatry is the use of brain imaging data to develop predictive models. Here we present two contributions to statistical methodology for this purpose. First, we propose and compare a set of wavelet-domain procedures for fitting generalized linear models with scalar responses and image predictors: sparse variants of principal component regression and of partial least squares, and the elastic net. Second, we consider assessing the contribution of image predictors over and above available scalar predictors, in particular via permutation tests and an extension of the idea of confounding to the case of functional or image predictors. …

Adaptive Pre-Specification In Randomized Trials With And Without Pair-Matching, Laura B. Balzer, Mark J. Van Der Laan, Maya L. Petersen

Laura B. Balzer

In randomized trials, adjustment for measured covariates during the analysis can reduce variance and increase power. To avoid misleading inference, the analysis plan must be pre-specified. However, it is unclear a priori which baseline covariates (if any) should be included in the analysis. Consider, for example, the Sustainable East Africa Research in Community Health (SEARCH) trial for HIV prevention and treatment. There are 16 matched pairs of communities and many potential adjustment variables, including region, HIV prevalence, male circumcision coverage and measures of community-level viral load. In this paper, we propose a rigorous procedure to data-adaptively select the adjustment set …

Targeted Estimation And Inference For The Sample Average Treatment Effect, Laura B. Balzer, Maya L. Petersen, Mark J. Van Der Laan

Laura B. Balzer

While the population average treatment effect has been the subject of extensive methods and applied research, less consideration has been given to the sample average treatment effect: the mean difference in the counterfactual outcomes for the study units. The sample parameter is easily interpretable and is arguably the most relevant when the study units are not representative of a greater population or when the exposure's impact is heterogeneous. Formally, the sample effect is not identifiable from the observed data distribution. Nonetheless, targeted maximum likelihood estimation (TMLE) can provide an asymptotically unbiased and efficient estimate of both the population and sample …

Matching Methods For Biomarker Evaluation: A Mapping With Causal Inference, Debashis Ghosh, Michael Sabel

Debashis Ghosh

In many medical settings, there is interest in evaluating the predictive ability of a candidate biomarker while adjusting appropriately for confounding factors. Recently, Janes and Pepe (2008, {\it Biometrics} 64: 1 -- 9) evaluated the effects of matching on classification accuracy for biomarkers. In this article, we note an analogy between the use of matching in causal inference with its role in the biomarker evaluation problem. This leads us to be able to import much of the literature on matching from causal inferential settings to the biomarker evaluation problem. This leads to a theoretical characterization of the bias properties of …

A Review Of Frequentist Tests For The 2x2 Binomial Trial, Chris Lloyd

Chris J. Lloyd

The 2x2 binomial trial is the simplest of data structures yet its statistical analysis and the issues it raises have been debated and revisited for over 70 years. Which analysis should biomedical researchers use in applications? In this review, we consider frequentist tests only, specifically tests with control size either exactly or very close to exactly. These procedures can be classified as conditional and unconditional. Amongst tests motivated by a conditional model, Lancaster’s mid-p and Liebermeister’s test are less conservative than Fisher’s classical test, but do not control type 1 error. Within the conditional framework, only Fisher’s test can be …

Prognostic And Predictive Directions For Clinical Trials, Debashis Ghosh

Debashis Ghosh

In many clinical trials, treatment effects can be quite heterogeneous across subgroups so that individuals in different subgroups can receive different benefits of the treatment. This can be quite important for the purposes of clinical decision-making purposes. In this article, we introduce a general concept of risk score that is motivated by potential outcomes consider- ations. The concepts of prognostic and predictive directions for outcome data are defined. Their basis is in the dimension reduction (DR) literature and can also be motivated by con- ditional independence assumptions. Under some conditions, one can use existing methods from the DR literature to …

Case Studies In Evaluating Time Series Prediction Models Using The Relative Mean Absolute Error, Nicholas G. Reich, Justin Lessler, Krzysztof Sakrejda, Stephen A. Lauer, Sopon Iamsirithaworn, Derek A T Cummings

Nicholas G Reich

Statistical prediction models inform decision-making processes in many real-world settings. Prior to using predictions in practice, one must rigorously test and validate candidate models to ensure that the proposed predictions have sufficient accuracy to be used in practice. In this paper, we present a framework for evaluating time series predictions that emphasizes computational simplicity and an intuitive interpretation using the relative mean absolute error metric. For a single time series, this metric enables comparisons of candidate model predictions against naive reference models, a method that can provide useful and standardized performance benchmarks. Additionally, in applications with multiple time series, this …

Adaptive Pair-Matching In Randomized Trials With Unbiased And Efficient Effect Estimation, Laura Balzer, M Petersen, M Van Der Laan, The Search Consortium

Laura B. Balzer

Quantile Rank Maps: A New Tool For Understanding Individual Brain Development, Huaihou Chen, Clare Kelly, F. Xavier Castellanos, Ye He, Xi-Nian Zuo, Philip T. Reiss

Philip T. Reiss

We propose a novel method for neurodevelopmental brain mapping that displays how an individual’s values for a quantity of interest compare with age-specific norms. By estimating smoothly age-varying distributions at a set of brain regions of interest, we derive age-dependent region-wise quantile ranks for a given individual, which can be presented in the form of a brain map. Such quantile rank maps could potentially be used for clinical screening. Bootstrap-based confidence intervals are proposed for the quantile rank estimates. We also propose a recalibrated Kolmogorov-Smirnov test for detecting group differences in the age-varying distribution. This test is shown to be …

Cross-Validation And Hypothesis Testing In Neuroimaging: An Irenic Comment On The Exchange Between Friston And Lindquist Et Al., Philip T. Reiss

Philip T. Reiss

The “ten ironic rules for statistical reviewers” presented by Friston (2012) prompted a rebuttal by Lindquist et al. (2013), which was followed by a rejoinder by Friston (2013). A key issue left unresolved in this discussion is the use of cross-validation to test the significance of predictive analyses. This note discusses the role that cross-validation-based and related hypothesis tests have come to play in modern data analyses, in neuroimaging and other fields. It is shown that such tests need not be suboptimal and can fill otherwise-unmet inferential needs.

Epidemiology Of Latency And Relapse In Plasmodium Vivax Malaria, Andrew A. Lover

Andrew Lover

Considerations For Comprehensive Analyses Of Sporozoite-Based Controlled Human Malaria Infection Studies, Andrew A. Lover

Andrew Lover

Short Report: Study Variability In Recent Human Challenge Experiments With Plasmodium Falciparum Sporozoites (Pfspz Challenge), Andrew A. Lover

Andrew Lover

Can Acute Dermal Systemic Toxicity Tests Be Replaced With Oral Tests? A Comparison Of Route-Specific Systemic Toxicity And Hazard Classifications Under The Globally Harmonized System Of Classification And Labelling Of Chemicals (Ghs), Nigel P. Moore, David J. Andrew, Donald L. Bjerke, Stuart Creton, David Dreher, Thomas Holmes, Pilar Prieto, Troy Seidle, Tim G. Rowan

Troy Seidle, PhD

Acute systemic toxicity data (LD50 values) and hazard classifications derived in the rat following oral administration and dermal application have been analysed to examine whether or not orally-derived hazard classification or LD50 values can be used to determine dermal hazard classification. Comparing the oral and dermal classifications for 335 substances derived from oral and dermal LD50 values respectively revealed 17% concordance, and indicated that 7% of substances would be classified less severely while 76% would be classified more severely if oral classifications were applied directly to the dermal route. In contrast, applying the oral LD50 values within the dermal classification …

An Overview Of Statistical Approaches For Comparative Effectiveness Research For Assessing In-Hospital Complications Of Percutaneous Coronary Interventions By Access Site, Lauren Kunz, Sherri Rose, Donna Spiegelman, Sharon-Lise Normand

Sherri Rose

No abstract provided.

Cluster Randomized Trials And Statistical Power, Stephen A. Lauer, Nicholas G. Reich

Nicholas G Reich

The cluster-randomized trial (CRT) is a common study design in public health research. In situations where dividing a group of individuals into treatment and controls is unethical or impossible, a CRT design maintains the strengths of a randomized study design. By comparing the outcomes of small populations (clusters), we can observe the impacts of interventions on the community as a whole. Public health researchers around the world have utilized CRTs to measure the effect of, for example, de-worming medication on school attendance, financial incentives on doctor absenteeism, and providing chlorine to waterholes. The CRT can be a potent tool, however …

Depicting Estimates Using The Intercept In Meta-Regression Models: The Moving Constant Technique, Blair T. Johnson Dr., Tania B. Huedo-Medina Dr.

Blair T. Johnson

In any scientific discipline, the ability to portray research patterns graphically often aids greatly in interpreting a phenomenon. In part to depict phenomena, the statistics and capabilities of meta-analytic models have grown increasingly sophisticated. Accordingly, this article details how to move the constant in weighted meta-analysis regression models (viz. “meta-regression”) to illuminate the patterns in such models across a range of complexities. Although it is commonly ignored in practice, the constant (or intercept) in such models can be indispensible when it is not relegated to its usual static role. The moving constant technique makes possible estimates and confidence intervals at …

Massively Parallel Nonparametric Regression, With An Application To Developmental Brain Mapping, Philip T. Reiss, Lei Huang, Yin-Hsiu Chen, Lan Huo, Thaddeus Tarpey, Maarten Mennes

Lei Huang

We propose a penalized spline approach to performing large numbers of parallel nonparametric analyses of either of two types: restricted likelihood ratio tests of a parametric regression model versus a general smooth alternative, and nonparametric regression. Compared with naively performing each analysis in turn, our techniques reduce computation time dramatically. Viewing the large collection of scatterplot smooths produced by our methods as functional data, we develop a clustering approach to summarize and visualize these results. Our approach is applicable to ultra-high-dimensional data, particularly data acquired by neuroimaging; we illustrate it with an analysis of developmental trajectories of functional connectivity at …

Adaptive Pair-Matching In The Search Trial And Estimation Of The Intervention Effect, Laura Balzer, Maya L. Petersen, Mark J. Van Der Laan

Laura B. Balzer

In randomized trials, pair-matching is an intuitive design strategy to protect study validity and to potentially increase study power. In a common design, candidate units are identified, and their baseline characteristics used to create the best n/2 matched pairs. Within the resulting pairs, the intervention is randomized, and the outcomes measured at the end of follow-up. We consider this design to be adaptive, because the construction of the matched pairs depends on the baseline covariates of all candidate units. As consequence, the observed data cannot be considered as n/2 independent, identically distributed (i.i.d.) pairs of units, as current practice assumes. …