Longitudinal Data Analysis and Time Series Commons^™

Early-Warning Alert Systems For Financial-Instability Detection: An Hmm-Driven Approach, Xing Gu

Electronic Thesis and Dissertation Repository

Regulators’ early intervention is crucial when the financial system is experiencing difficulties. Financial stability must be preserved to avert banks’ bailouts, which hugely drain government's financial resources. Detecting in advance periods of financial crisis entails the development and customisation of accurate and robust quantitative techniques. The goal of this thesis is to construct automated systems via the interplay of various mathematical and statistical methodologies to signal financial instability episodes in the near-term horizon. These signal alerts could provide regulatory bodies with the capacity to initiate appropriate response that will thwart or at least minimise the occurrence of a financial crisis. …

Modelling The Common Risk Among Equities Using A New Time Series Model, Jingjia Chu

Electronic Thesis and Dissertation Repository

A new additive structure of multivariate GARCH model is proposed where the dynamic changes of the conditional correlation between the stocks are aggregated by the common risk term. The observable sequence is divided into two parts, a common risk term and an individual risk term, both following a GARCH type structure. The conditional volatility of each stock will be the sum of these two conditional variance terms. All the conditional volatility of the stock can shoot up together because a sudden peak of the common volatility is a sign of the system shock.

We provide sufficient conditions for strict stationarity …

Models For Hsv Shedding Must Account For Two Levels Of Overdispersion, Amalia Magaret

UW Biostatistics Working Paper Series

We have frequently implemented crossover studies to evaluate new therapeutic interventions for genital herpes simplex virus infection. The outcome measured to assess the efficacy of interventions on herpes disease severity is the viral shedding rate, defined as the frequency of detection of HSV on the genital skin and mucosa. We performed a simulation study to ascertain whether our standard model, which we have used previously, was appropriately considering all the necessary features of the shedding data to provide correct inference. We simulated shedding data under our standard, validated assumptions and assessed the ability of 5 different models to reproduce the …

Functional Car Models For Spatially Correlated Functional Datasets, Lin Zhang, Veerabhadran Baladandayuthapani, Hongxiao Zhu, Keith A. Baggerly, Tadeusz Majewski, Bogdan Czerniak, Jeffrey S. Morris

Jeffrey S. Morris

We develop a functional conditional autoregressive (CAR) model for spatially correlated data for which functions are collected on areal units of a lattice. Our model performs functional response regression while accounting for spatial correlations with potentially nonseparable and nonstationary covariance structure, in both the space and functional domains. We show theoretically that our construction leads to a CAR model at each functional location, with spatial covariance parameters varying and borrowing strength across the functional domain. Using basis transformation strategies, the nonseparable spatial-functional model is computationally scalable to enormous functional datasets, generalizable to different basis functions, and can be used on …

Shrinkage Estimation For Multivariate Hidden Markov Mixture Models, Mark Fiecas, Jürgen Franke, Rainer Von Sachs, Joseph Tadjuidje

Mark Fiecas

Optimal Restricted Estimation For More Efficient Longitudinal Causal Inference, Edward Kennedy, Marshall Joffe, Dylan Small

Edward H. Kennedy

Efficient semiparametric estimation of longitudinal causal effects is often analytically or computationally intractable. We propose a novel restricted estimation approach for increasing efficiency, which can be used with other techniques, is straightforward to implement, and requires no additional modeling assumptions.

On Likelihood Ratio Tests When Nuisance Parameters Are Present Only Under The Alternative, Cz Di, K-Y Liang

Chongzhi Di

In parametric models, when one or more parameters disappear under the null hypothesis, the likelihood ratio test statistic does not converge to chi-square distributions. Rather, its limiting distribution is shown to be equivalent to that of the supremum of a squared Gaussian process. However, the limiting distribution is analytically intractable for most of examples, and approximation or simulation based methods must be used to calculate the p values. In this article, we investigate conditions under which the asymptotic distributions have analytically tractable forms, based on the principal component decomposition of Gaussian processes. When these conditions are not satisfied, the principal …

Spectral Density Shrinkage For High-Dimensional Time Series, Mark Fiecas, Rainer Von Sachs

Mark Fiecas

Targeted Maximum Likelihood Estimation For Dynamic Treatment Regimes In Sequential Randomized Controlled Trials, Paul Chaffee, Mark J. Van Der Laan

Paul H. Chaffee

Sequential Randomized Controlled Trials (SRCTs) are rapidly becoming essential tools in the search for optimized treatment regimes in ongoing treatment settings. Analyzing data for multiple time-point treatments with a view toward optimal treatment regimes is of interest in many types of afflictions: HIV infection, Attention Deficit Hyperactivity Disorder in children, leukemia, prostate cancer, renal failure, and many others. Methods for analyzing data from SRCTs exist but they are either inefficient or suffer from the drawbacks of estimating equation methodology. We describe an estimation procedure, targeted maximum likelihood estimation (TMLE), which has been fully developed and implemented in point treatment settings, …

Proportional Mean Residual Life Model For Right-Censored Length-Biased Data, Gary Kwun Chuen Chan, Ying Qing Chen, Chongzhi Di

Chongzhi Di

To study disease association with risk factors in epidemiologic studies, cross-sectional sampling is often more focused and less costly for recruiting study subjects who have already experienced initiating events. For time-to-event outcome, however, such a sampling strategy may be length-biased. Coupled with censoring, analysis of length-biased data can be quite challenging, due to the so-called “induced informative censoring” in which the survival time and censoring time are correlated through a common backward recurrence time. We propose to use the proportional mean residual life model of Oakes and Dasu (1990) for analysis of censored length-biased survival data. Several nonstandard data structures, …

Targeted Maximum Likelihood Estimation For Dynamic Treatment Regimes In Sequential Randomized Controlled Trials, Paul Chaffee, Mark J. Van Der Laan

U.C. Berkeley Division of Biostatistics Working Paper Series

Sequential Randomized Controlled Trials (SRCTs) are rapidly becoming essential tools in the search for optimized treatment regimes in ongoing treatment settings. Analyzing data for multiple time-point treatments with a view toward optimal treatment regimes is of interest in many types of afflictions: HIV infection, Attention Deficit Hyperactivity Disorder in children, leukemia, prostate cancer, renal failure, and many others. Methods for analyzing data from SRCTs exist but they are either inefficient or suffer from the drawbacks of estimating equation methodology. We describe an estimation procedure, targeted maximum likelihood estimation (TMLE), which has been fully developed and implemented in point treatment settings, …

Multilevel Latent Class Models With Dirichlet Mixing Distribution, Chong-Zhi Di, Karen Bandeen-Roche

Chongzhi Di

Latent class analysis (LCA) and latent class regression (LCR) are widely used for modeling multivariate categorical outcomes in social sciences and biomedical studies. Standard analyses assume data of different respondents to be mutually independent, excluding application of the methods to familial and other designs in which participants are clustered. In this paper, we consider multilevel latent class models, in which sub-population mixing probabilities are treated as random effects that vary among clusters according to a common Dirichlet distribution. We apply the Expectation-Maximization (EM) algorithm for model fitting by maximum likelihood (ML). This approach works well, but is computationally intensive when …

Likelihood Ratio Testing For Admixture Models With Application To Genetic Linkage Analysis, Chong-Zhi Di, Kung-Yee Liang

Chongzhi Di

We consider likelihood ratio tests (LRT) and their modifications for homogeneity in admixture models. The admixture model is a special case of two component mixture model, where one component is indexed by an unknown parameter while the parameter value for the other component is known. It has been widely used in genetic linkage analysis under heterogeneity, in which the kernel distribution is binomial. For such models, it is long recognized that testing for homogeneity is nonstandard and the LRT statistic does not converge to a conventional 2 distribution. In this paper, we investigate the asymptotic behavior of the LRT for …

Sequence Comparison And Stochastic Model Based On Multi-Order Markov Models, Xiang Fang

Department of Statistics: Dissertations, Theses, and Student Work

This dissertation presents two statistical methodologies developed on multi-order Markov models. First, we introduce an alignment-free sequence comparison method, which represents a sequence using a multi-order transition matrix (MTM). The MTM contains information of multi-order dependencies and provides a comprehensive representation of the heterogeneous composition within a sequence. Based on the MTM, a distance measure is developed for pair-wise comparison of sequences. The new method is compared with the traditional maximum likelihood (ML) method, the complete composition vector (CCV) method and the improved version of the complete composition vector (ICCV) method using simulated sequences. We further illustrate the application of …

Spatial Cluster Detection For Repeatedly Measured Outcomes While Accounting For Residential History, Andrea J. Cook, Diane Gold, Yi Li

Harvard University Biostatistics Working Paper Series

No abstract provided.

Spatial Cluster Detection For Weighted Outcomes Using Cumulative Geographic Residuals, Andrea J. Cook, Yi Li, David Arterburn, Ram C. Tiwari

Harvard University Biostatistics Working Paper Series

No abstract provided.

Multilevel Functional Principal Component Analysis, Chong-Zhi Di, Ciprian M. Crainiceanu, Brian S. Caffo, Naresh M. Punjabi

Chongzhi Di

The Sleep Heart Health Study (SHHS) is a comprehensive landmark study of sleep and its impacts on health outcomes. A primary metric of the SHHS is the in-home polysomnogram, which includes two electroencephalographic (EEG) channels for each subject, at two visits. The volume and importance of this data presents enormous challenges for analysis. To address these challenges, we introduce multilevel functional principal component analysis (MFPCA), a novel statistical methodology designed to extract core intra- and inter-subject geometric components of multilevel functional data. Though motivated by the SHHS, the proposed methodology is generally applicable, with potential relevance to many modern scientific …

Nonparametric Signal Extraction And Measurement Error In The Analysis Of Electroencephalographic Activity During Sleep, Ciprian M. Crainiceanu, Brian S. Caffo, Chong-Zhi Di, Naresh M. Punjabi

Chongzhi Di

We introduce methods for signal and associated variability estimation based on hierarchical nonparametric smoothing with application to the Sleep Heart Health Study (SHHS). SHHS is the largest electroencephalographic (EEG) collection of sleep-related data, which contains, at each visit, two quasi-continuous EEG signals for each subject. The signal features extracted from EEG data are then used in second level analyses to investigate the relation between health, behavioral, or biometric outcomes and sleep. Using subject specific signals estimated with known variability in a second level regression becomes a nonstandard measurement error problem.We propose and implement methods that take into account cross-sectional and …

Generalized Multilevel Functional Regression, Ciprian M. Crainiceanu, Ana-Maria Staicu, Chong-Zhi Di

Chongzhi Di

We introduce Generalized Multilevel Functional Linear Models (GMFLMs), a novel statistical framework for regression models where exposure has a multilevel functional structure. We show that GMFLMs are, in fact, generalized multilevel mixed models. Thus, GMFLMs can be analyzed using the mixed effects inferential machinery and can be generalized within a well-researched statistical framework. We propose and compare two methods for inference: (1) a two-stage frequentist approach; and (2) a joint Bayesian analysis. Our methods are motivated by and applied to the Sleep Heart Health Study, the largest community cohort study of sleep. However, our methods are general and easy to …

Detailed Version: Analyzing Direct Effects In Randomized Trials With Secondary Interventions: An Application To Hiv Prevention Trials, Michael A. Rosenblum, Nicholas P. Jewell, Mark J. Van Der Laan, Stephen Shiboski, Ariane Van Der Straten, Nancy Padian

U.C. Berkeley Division of Biostatistics Working Paper Series

This is the detailed technical report that accompanies the paper “Analyzing Direct Effects in Randomized Trials with Secondary Interventions: An Application to HIV Prevention Trials” (an unpublished, technical report version of which is available online at http://www.bepress.com/ucbbiostat/paper223).

The version here gives full details of the models for the time-dependent analysis, and presents further results in the data analysis section. The Methods for Improving Reproductive Health in Africa (MIRA) trial is a recently completed randomized trial that investigated the effect of diaphragm and lubricant gel use in reducing HIV infection among susceptible women. 5,045 women were randomly assigned to either the …

Analyzing Direct Effects In Randomized Trials With Secondary Interventions , Michael Rosenblum, Nicholas P. Jewell, Mark J. Van Der Laan, Stephen Shiboski, Ariane Van Der Straten, Nancy Padian

U.C. Berkeley Division of Biostatistics Working Paper Series

The Methods for Improving Reproductive Health in Africa (MIRA) trial is a recently completed randomized trial that investigated the effect of diaphragm and lubricant gel use in reducing HIV infection among susceptible women. 5,045 women were randomly assigned to either the active treatment arm or not. Additionally, all subjects in both arms received intensive condom counselling and provision, the "gold standard" HIV prevention barrier method. There was much lower reported condom use in the intervention arm than in the control arm, making it difficult to answer important public health questions based solely on the intention-to-treat analysis. We adapt an analysis …

Bayesian Hidden Markov Modeling Of Array Cgh Data, Subharup Guha, Yi Li, Donna Neuberg

Harvard University Biostatistics Working Paper Series

Genomic alterations have been linked to the development and progression of cancer. The technique of Comparative Genomic Hybridization (CGH) yields data consisting of fluorescence intensity ratios of test and reference DNA samples. The intensity ratios provide information about the number of copies in DNA. Practical issues such as the contamination of tumor cells in tissue specimens and normalization errors necessitate the use of statistics for learning about the genomic alterations from array-CGH data. As increasing amounts of array CGH data become available, there is a growing need for automated algorithms for characterizing genomic profiles. Specifically, there is a need for …

Estimating A Treatment Effect With Repeated Measurements Accounting For Varying Effectiveness Duration, Ying Qing Chen, Jingrong Yang, Su-Chun Cheng

UW Biostatistics Working Paper Series

To assess treatment efficacy in clinical trials, certain clinical outcomes are repeatedly measured for same subject over time. They can be regarded as function of time. The difference in their mean functions between the treatment arms usually characterises a treatment effect. Due to the potential existence of subject-specific treatment effectiveness lag and saturation times, erosion of treatment effect in the difference may occur during the observation period of time. Instead of using ad hoc parametric or purely nonparametric time-varying coefficients in statistical modeling, we first propose to model the treatment effectiveness durations, which are the varying time intervals between the …

Semiparametric Estimation In General Repeated Measures Problems, Xihong Lin, Raymond J. Carroll

Harvard University Biostatistics Working Paper Series

This paper considers a wide class of semiparametric problems with a parametric part for some covariate effects and repeated evaluations of a nonparametric function. Special cases in our approach include marginal models for longitudinal/clustered data, conditional logistic regression for matched case-control studies, multivariate measurement error models, generalized linear mixed models with a semiparametric component, and many others. We propose profile-kernel and backfitting estimation methods for these problems, derive their asymptotic distributions, and show that in likelihood problems the methods are semiparametric efficient. While generally not true, with our methods profiling and backfitting are asymptotically equivalent. We also consider pseudolikelihood methods …

Direct Effect Models, 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 for treatment and the intermediate variable, Robins & Greenland (1992) define an individual direct effect as the counterfactual effect of …

Causal Inference In Longitudinal Studies With History-Restricted Marginal Structural Models, Romain Neugebauer, Mark J. Van Der Laan, Ira B. Tager

U.C. Berkeley Division of Biostatistics Working Paper Series

Causal Inference based on Marginal Structural Models (MSMs) is particularly attractive to subject-matter investigators because MSM parameters provide explicit representations of causal effects. We introduce History-Restricted Marginal Structural Models (HRMSMs) for longitudinal data for the purpose of defining causal parameters which may often be better suited for Public Health research. This new class of MSMs allows investigators to analyze the causal effect of a treatment on an outcome based on a fixed, shorter and user-specified history of exposure compared to MSMs. By default, the latter represents the treatment causal effect of interest based on a treatment history defined by the …

A Bayesian Mixture Model Relating Dose To Critical Organs And Functional Complication In 3d Conformal Radiation Therapy, Tim Johnson, Jeremy Taylor, Randall K. Ten Haken, Avraham Eisbruch

The University of Michigan Department of Biostatistics Working Paper Series

A goal of radiation therapy is to deliver maximum dose to the target tumor while minimizing complications due to irradiation of critical organs. Technological advances in 3D conformal radiation therapy has allowed great strides in realizing this goal, however complications may still arise. Critical organs may be adjacent to tumors or in the path of the radiation beam. Several mathematical models have been proposed that describe a relationship between dose and observed functional complication, however only a few published studies have successfully fit these models to data using modern statistical methods which make efficient use of the data. One complication …

Cholesky Residuals For Assessing Normal Errors In A Linear Model With Correlated Outcomes: Technical Report, E. Andres Houseman, Louise Ryan, Brent Coull

Harvard University Biostatistics Working Paper Series

Despite the widespread popularity of linear models for correlated outcomes (e.g. linear mixed models and time series models), distribution diagnostic methodology remains relatively underdeveloped in this context. In this paper we present an easy-to-implement approach that lends itself to graphical displays of model fit. Our approach involves multiplying the estimated margional residual vector by the Cholesky decomposition of the inverse of the estimated margional variance matrix. The resulting "rotated" residuals are used to construct an empirical cumulative distribution function and pointwise standard errors. The theoretical framework, including conditions and asymptotic properties, involves technical details that are motivated by Lange and …

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 …

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 …