Open Access. Powered by Scholars. Published by Universities.®

Physical Sciences and Mathematics Commons

Open Access. Powered by Scholars. Published by Universities.®

Articles 1 - 19 of 19

Full-Text Articles in Physical Sciences and Mathematics

Nonlinear Mixed-Effects Models For Hiv Viral Load Trajectories Before And After Antiretroviral Therapy Interruption, Incorporating Left Censoring, Sihaoyu Gao, Lang Wu, Tingting Yu, Roger Kouyos, Huldrych F. Gunthard, Rui Wang Jan 2022

Nonlinear Mixed-Effects Models For Hiv Viral Load Trajectories Before And After Antiretroviral Therapy Interruption, Incorporating Left Censoring, Sihaoyu Gao, Lang Wu, Tingting Yu, Roger Kouyos, Huldrych F. Gunthard, Rui Wang

Harvard University Biostatistics Working Paper Series

Characterizing features of the viral rebound trajectories and identifying host, virological, and immunological factors that are predictive of the viral rebound trajectories are central to HIV cure research. In this paper, we investigate if key features of HIV viral decay and CD4 trajectories during antiretroviral therapy (ART) are associated with characteristics of HIV viral rebound following ART interruption. Nonlinear mixed effect (NLME) models are used to model viral load trajectories before and following ART interruption, incorporating left censoring due to lower detection limits of viral load assays. A stochastic approximation EM (SAEM) algorithm is used for parameter estimation and inference. …


Variable-Domain Functional Regression For Modeling Icu Data, Jonathan E. Gellar, Elizabeth Colantuoni, Dale M. Needham, Ciprian M. Crainiceanu May 2014

Variable-Domain Functional Regression For Modeling Icu Data, Jonathan E. Gellar, Elizabeth Colantuoni, Dale M. Needham, Ciprian M. Crainiceanu

Johns Hopkins University, Dept. of Biostatistics Working Papers

We introduce a class of scalar-on-function regression models with subject-specific functional predictor domains. The fundamental idea is to consider a bivariate functional parameter that depends both on the functional argument and on the width of the functional predictor domain. Both parametric and nonparametric models are introduced to fit the functional coefficient. The nonparametric model is theoretically and practically invariant to functional support transformation, or support registration. Methods were motivated by and applied to a study of association between daily measures of the Intensive Care Unit (ICU) Sequential Organ Failure Assessment (SOFA) score and two outcomes: in-hospital mortality, and physical impairment …


Mediation Analysis With Time-Varying Exposures And Mediators, Tyler J. Vanderweele, Eric Tchetgen Tchetgen Mar 2014

Mediation Analysis With Time-Varying Exposures And Mediators, Tyler J. Vanderweele, Eric Tchetgen Tchetgen

Harvard University Biostatistics Working Paper Series

In this paper we consider mediation analysis when exposures and mediators vary over time. We give non-parametric identification results, discuss parametric implementation, and also provide a weighting approach to direct and indirect effects based on combining the results of two marginal structural models. We also discuss how our results give rise to a causal interpretation of the effect estimates produced from longitudinal structural equation models. When there are no time-varying confounders affected by prior exposure and mediator values, identification of direct and indirect effects is achieved by a longitudinal version of Pearl's mediation formula. When there are time-varying confounders affected …


Regression Trees For Longitudinal Data, Madan Gopal Kundu, Jaroslaw Harezlak Sep 2013

Regression Trees For Longitudinal Data, Madan Gopal Kundu, Jaroslaw Harezlak

COBRA Preprint Series

Often when a longitudinal change is studied in a population of interest we find that changes over time are heterogeneous (in terms of time and/or covariates' effect) and a traditional linear mixed effect model [Laird and Ware, 1982] on the entire population assuming common parametric form for covariates and time may not be applicable to the entire population. This is usually the case in studies when there are many possible predictors influencing the response trajectory. For example, Raudenbush [2001] used depression as an example to argue that it is incorrect to assume that all the people in a given population …


Vertically Shifted Mixture Models For Clustering Longitudinal Data By Shape, Brianna C. Heggeseth, Nicholas P. Jewell Mar 2013

Vertically Shifted Mixture Models For Clustering Longitudinal Data By Shape, Brianna C. Heggeseth, Nicholas P. Jewell

U.C. Berkeley Division of Biostatistics Working Paper Series

Longitudinal studies play a prominent role in health, social and behavioral sciences as well as in the biological sciences, economics, and marketing. By following subjects over time, temporal changes in an outcome of interest can be directly observed and studied. An important question concerns the existence of distinct trajectory patterns. One way to determine these distinct patterns is through cluster analysis, which seeks to separate objects (subjects, patients, observational units) into homogeneous groups. Many methods have been adapted for longitudinal data, but almost all of them fail to explicitly group trajectories according to distinct pattern shapes. To fulfill the need …


Likelihood Ratio Tests For The Mean Structure Of Correlated Functional Processes, Ana-Maria Staicu, Yingxing Li, Ciprian Crainiceanu, David M. Ruppert Nov 2012

Likelihood Ratio Tests For The Mean Structure Of Correlated Functional Processes, Ana-Maria Staicu, Yingxing Li, Ciprian Crainiceanu, David M. Ruppert

Johns Hopkins University, Dept. of Biostatistics Working Papers

The paper introduces a general framework for testing hypotheses about the structure of the mean function of complex functional processes. Important particular cases of the proposed framework are: 1) testing the null hypotheses that the mean of a functional process is parametric against a nonparametric alternative; and 2) testing the null hypothesis that the means of two possibly correlated functional processes are equal or differ by only a simple parametric function. A global pseudo likelihood ratio test is proposed and its asymptotic distribution is derived. The size and power properties of the test are confirmed in realistic simulation scenarios. Finite …


Longitudinal Functional Models With Structured Penalties, Madan G. Kundu, Jaroslaw Harezlak, Timothy W. Randolph Nov 2012

Longitudinal Functional Models With Structured Penalties, Madan G. Kundu, Jaroslaw Harezlak, Timothy W. Randolph

Johns Hopkins University, Dept. of Biostatistics Working Papers

Collection of functional data is becoming increasingly common including longitudinal observations in many studies. For example, we use magnetic resonance (MR) spectra collected over a period of time from late stage HIV patients. MR spectroscopy (MRS) produces a spectrum which is a mixture of metabolite spectra, instrument noise and baseline profile. Analysis of such data typically proceeds in two separate steps: feature extraction and regression modeling. In contrast, a recently-proposed approach, called partially empirical eigenvectors for regression (PEER) (Randolph, Harezlak and Feng, 2012), for functional linear models incorporates a priori knowledge via a scientifically-informed penalty operator in the regression function …


Longitudinal Analysis Of Spatiotemporal Processes: A Case Study Of Dynamic Contrast-Enhanced Magnetic Resonance Imaging In Multiple Sclerosis, Russell T. Shinohara, Ciprian M. Crainiceanu, Brian S. Caffo, Daniel S. Reich Sep 2011

Longitudinal Analysis Of Spatiotemporal Processes: A Case Study Of Dynamic Contrast-Enhanced Magnetic Resonance Imaging In Multiple Sclerosis, Russell T. Shinohara, Ciprian M. Crainiceanu, Brian S. Caffo, Daniel S. Reich

Johns Hopkins University, Dept. of Biostatistics Working Papers

Multiple sclerosis (MS) is an immune-mediated disease in which inflammatory lesions form in the brain. In many active MS lesions, the blood-brain barrier (BBB) is disrupted and blood flows into white matter; this disruption may be related to morbidity and disability. Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) allows quantitative study of blood flow and permeability dynamics throughout the brain. This technique involves a subject being imaged sequentially during a study visit as an intravenously administered contrast agent flows into the brain. In regions where flow is abnormal, such as white matter lesions, this allows the quantification of the BBB damage. …


Marginal Regression Modeling Under Irregular, Biased Sampling, Petra Buzkova, Thomas Lumley Sep 2005

Marginal Regression Modeling Under Irregular, Biased Sampling, Petra Buzkova, Thomas Lumley

UW Biostatistics Working Paper Series

In longitudinal studies observations are often obtained at continuous subject-specific times. Frequently the availability of outcome data may be related to the outcome measure or other covariates that are related to the outcome measure. Under such biased sampling designs unadjusted regression analysis yield biased estimates. Building on the work of Lin & Ying (2001) that integrates counting processes techniques with longitudinal data settings we propose a class of estimators that can handle biased sampling. We call those estimators ``inverse--intensity--rate--ratio--weighted'' (IIRR) estimators. Of major focus is a mean--response model where we examine the marginal effect of the covariate X at time …


Longitudinal Data Analysis For Generalized Linear Models Under Irregular, Biased Sampling: Situations With Follow-Up Dependent On Outcome Or Auxiliary Outcome-Related Variables, Petra Buzkova, Thomas Lumley Sep 2005

Longitudinal Data Analysis For Generalized Linear Models Under Irregular, Biased Sampling: Situations With Follow-Up Dependent On Outcome Or Auxiliary Outcome-Related Variables, Petra Buzkova, Thomas Lumley

UW Biostatistics Working Paper Series

In longitudinal studies, observations are often obtained at subject-specific observation times. Those times can be continuous times, not at a set of prespecified times. Frequently the observation times may be related to the outcome measure or other auxiliary variables that are related to the outcome measure but undesirable to condition upon in the regression model for outcome. Regression analysis unadjusted for such sampling designs yield biased estimates. Based on estimating equations, we propose a class of estimators in generalized linear regression models that can handle biased sampling under continuous observation times. We call those estimators ``inverse--intensity rate--ratio--weighted'' (IIRR) estimators. The …


Semiparametric Loglinear Regression For Longitudinal Measurements Subject To Irregular, Biased Follow-Up, Petra Buzkova, Thomas Lumley Sep 2005

Semiparametric Loglinear Regression For Longitudinal Measurements Subject To Irregular, Biased Follow-Up, Petra Buzkova, Thomas Lumley

UW Biostatistics Working Paper Series

We propose a method for analysis of loglinear regression models for longitudinal data that are subject to continuous and irregular follow-up. Frequently, if the follow-up is irregular, the availability of outcome data may be related to the outcome measure or other covariates that are related to the outcome measure. Under such biased sampling designs unadjusted regression analysis yield biased estimates. We examine the marginal association of the covariates X at time t and the logarithm of the mean of response Y at time t. We focus on semiparametric regression with unspecified baseline function of time. To predict the follow-up times …


G-Computation Estimation Of Nonparametric Causal Effects On Time-Dependent Mean Outcomes In Longitudinal Studies, Romain Neugebauer, Mark J. Van Der Laan Jul 2005

G-Computation Estimation Of Nonparametric Causal Effects On Time-Dependent Mean Outcomes In Longitudinal Studies, Romain Neugebauer, Mark J. Van Der Laan

U.C. Berkeley Division of Biostatistics Working Paper Series

Two approaches to Causal Inference based on Marginal Structural Models (MSM) have been proposed. They provide different representations of causal effects with distinct causal parameters. Initially, a parametric MSM approach to Causal Inference was developed: it relies on correct specification of a parametric MSM. Recently, a new approach based on nonparametric MSM was introduced. This later approach does not require the assumption of a correctly specified MSM and thus is more realistic if one believes that correct specification of a parametric MSM is unlikely in practice. However, this approach was described only for investigating causal effects on mean outcomes collected …


History-Adjusted Marginal Structural Models And Statically-Optimal Dynamic Treatment Regimes, Mark J. Van Der Laan, Maya L. Petersen Sep 2004

History-Adjusted Marginal Structural Models And Statically-Optimal Dynamic Treatment Regimes, Mark J. Van Der Laan, Maya L. Petersen

U.C. Berkeley Division of Biostatistics Working Paper Series

Marginal structural models (MSM) provide a powerful tool for estimating the causal effect of a treatment. These models, introduced by Robins, model the marginal distributions of treatment-specific counterfactual outcomes, possibly conditional on a subset of the baseline covariates. Marginal structural models are particularly useful in the context of longitudinal data structures, in which each subject's treatment and covariate history are measured over time, and an outcome is recorded at a final time point. However, the utility of these models for some applications has been limited by their inability to incorporate modification of the causal effect of treatment by time-varying covariates. …


Estimation Of Direct And Indirect Causal Effects In Longitudinal Studies, Mark J. Van Der Laan, Maya L. Petersen Aug 2004

Estimation Of Direct And Indirect Causal Effects In Longitudinal Studies, Mark J. Van Der Laan, Maya L. Petersen

U.C. Berkeley Division of Biostatistics Working Paper Series

The causal effect of a treatment on an outcome is generally mediated by several intermediate variables. Estimation of the component of the causal effect of a treatment that is mediated by a given intermediate variable (the indirect effect of the treatment), and the component that is not mediated by that intermediate variable (the direct effect of the treatment) is often relevant to mechanistic understanding and to the design of clinical and public health interventions. Under the assumption of no-unmeasured confounders, Robins & Greenland (1992) and Pearl (2000), develop two identifiability results for direct and indirect causal effects. They define an …


Marginal Modeling Of Multilevel Binary Data With Time-Varying Covariates, Diana Miglioretti, Patrick Heagerty Dec 2003

Marginal Modeling Of Multilevel Binary Data With Time-Varying Covariates, Diana Miglioretti, Patrick Heagerty

UW Biostatistics Working Paper Series

We propose and compare two approaches for regression analysis of multilevel binary data when clusters are not necessarily nested: a GEE method that relies on a working independence assumption coupled with a three-step method for obtaining empirical standard errors; and a likelihood-based method implemented using Bayesian computational techniques. Implications of time-varying endogenous covariates are addressed. The methods are illustrated using data from the Breast Cancer Surveillance Consortium to estimate mammography accuracy from a repeatedly screened population.


Equivalent Kernels Of Smoothing Splines In Nonparametric Regression For Clustered/Longitudinal Data, Xihong Lin, Naisyin Wang, Alan H. Welsh, Raymond J. Carroll Sep 2003

Equivalent Kernels Of Smoothing Splines In Nonparametric Regression For Clustered/Longitudinal Data, Xihong Lin, Naisyin Wang, Alan H. Welsh, Raymond J. Carroll

The University of Michigan Department of Biostatistics Working Paper Series

We compare spline and kernel methods for clustered/longitudinal data. For independent data, it is well known that kernel methods and spline methods are essentially asymptotically equivalent (Silverman, 1984). However, the recent work of Welsh, et al. (2002) shows that the same is not true for clustered/longitudinal data. First, conventional kernel methods fail to account for the within- cluster correlation, while spline methods are able to account for this correlation. Second, kernel methods and spline methods were found to have different local behavior, with conventional kernels being local and splines being non-local. To resolve these differences, we show that a smoothing …


Histospline Method In Nonparametric Regression Models With Application To Clustered/Longitudinal Data, Raymond J. Carroll, Peter Hall, Tatiyana V. Apanasovich, Xihong Lin Sep 2003

Histospline Method In Nonparametric Regression Models With Application To Clustered/Longitudinal Data, Raymond J. Carroll, Peter Hall, Tatiyana V. Apanasovich, Xihong Lin

The University of Michigan Department of Biostatistics Working Paper Series

Kernel and smoothing methods for nonparametric function and curve estimation have been particularly successful in "standard" settings, where function values are observed subject to independent errors. However, when aspects of the function are known parametrically, or where the sampling scheme has significant structure, it can be quite difficult to adapt standard methods in such a way that they retain good statistical performance and continue to enjoy easy computability and good numerical properties. In particular, when using local linear modeling it is often awkward to both respect the sampling scheme and produce an estimator with good variance properties, without resorting to …


Efficient Semiparametric Marginal Estimation For Longitudinal/Clustered Data, Naisyin Wang, Raymond J. Carroll, Xihong Lin Sep 2003

Efficient Semiparametric Marginal Estimation For Longitudinal/Clustered Data, Naisyin Wang, Raymond J. Carroll, Xihong Lin

The University of Michigan Department of Biostatistics Working Paper Series

We consider marginal generalized semiparametric partially linear models for clustered data. Lin and Carroll (2001a) derived the semiparametric efficinet score funtion for this problem in the mulitvariate Gaussian case, but they were unable to contruct a semiparametric efficient estimator that actually achieved the semiparametric information bound. We propose such an estimator here and generalize the work to marginal generalized partially liner models. Asymptotic relative efficincies of the estimation or throughout are investigated. The finite sample performance of these estimators is evaluated through simulations and illustrated using a longtiudinal CD4 count data set. Both theoretical and numerical results indicate that properly …


Double Robust Estimation In Longitudinal Marginal Structural Models, Zhuo Yu, Mark J. Van Der Laan Jun 2003

Double Robust Estimation In Longitudinal Marginal Structural Models, Zhuo Yu, Mark J. Van Der Laan

U.C. Berkeley Division of Biostatistics Working Paper Series

Consider estimation of causal parameters in a marginal structural model for the discrete intensity of the treatment specific counting process (e.g. hazard of a treatment specific survival time) based on longitudinal observational data on treatment, covariates and survival. We assume the sequential randomization assumption (SRA) on the treatment assignment mechanism and the so called experimental treatment assignment assumption which is needed to identify the causal parameters from the observed data distribution. Under SRA, the likelihood of the observed data structure factorizes in the auxiliary treatment mechanism and the partial likelihood consisting of the product over time of conditional distributions of …