Improved testing inference in mixed linear models

Mixed linear models are commonly used in repeated measures studies. They account for the dependence amongst observations obtained from the same experimental unit. Oftentimes, the number of observations is small, and it is thus important to use inference strategies that incorporate small sample corrections. In this paper, we develop modified versions of the likelihood ratio test for fixed effects inference in mixed linear models. In particular, we derive a Bartlett correction to such a test and also to a test obtained from a modified profile likelihood function. Our results generalize those in Zucker et al. (Journal of the Royal Statistical Society B, 2000, 62, 827-838) by allowing the parameter of interest to be vector-valued. Additionally, our Bartlett corrections allow for random effects nonlinear covariance matrix structure. We report numerical evidence which shows that the proposed tests display superior finite sample behavior relative to the standard likelihood ratio test. An application is also presented and discussed.Comment: 17 pages, 1 figur

Fitting Linear Mixed-Effects Models using lme4

Maximum likelihood or restricted maximum likelihood (REML) estimates of the parameters in linear mixed-effects models can be determined using the lmer function in the lme4 package for R. As for most model-fitting functions in R, the model is described in an lmer call by a formula, in this case including both fixed- and random-effects terms. The formula and data together determine a numerical representation of the model from which the profiled deviance or the profiled REML criterion can be evaluated as a function of some of the model parameters. The appropriate criterion is optimized, using one of the constrained optimization functions in R, to provide the parameter estimates. We describe the structure of the model, the steps in evaluating the profiled deviance or REML criterion, and the structure of classes or types that represents such a model. Sufficient detail is included to allow specialization of these structures by users who wish to write functions to fit specialized linear mixed models, such as models incorporating pedigrees or smoothing splines, that are not easily expressible in the formula language used by lmer.Comment: 51 pages, including R code, and an appendi

Spike-and-Slab Priors for Function Selection in Structured Additive Regression Models

Structured additive regression provides a general framework for complex Gaussian and non-Gaussian regression models, with predictors comprising arbitrary combinations of nonlinear functions and surfaces, spatial effects, varying coefficients, random effects and further regression terms. The large flexibility of structured additive regression makes function selection a challenging and important task, aiming at (1) selecting the relevant covariates, (2) choosing an appropriate and parsimonious representation of the impact of covariates on the predictor and (3) determining the required interactions. We propose a spike-and-slab prior structure for function selection that allows to include or exclude single coefficients as well as blocks of coefficients representing specific model terms. A novel multiplicative parameter expansion is required to obtain good mixing and convergence properties in a Markov chain Monte Carlo simulation approach and is shown to induce desirable shrinkage properties. In simulation studies and with (real) benchmark classification data, we investigate sensitivity to hyperparameter settings and compare performance to competitors. The flexibility and applicability of our approach are demonstrated in an additive piecewise exponential model with time-varying effects for right-censored survival times of intensive care patients with sepsis. Geoadditive and additive mixed logit model applications are discussed in an extensive appendix

Simultaneous inference for misaligned multivariate functional data

We consider inference for misaligned multivariate functional data that represents the same underlying curve, but where the functional samples have systematic differences in shape. In this paper we introduce a new class of generally applicable models where warping effects are modeled through nonlinear transformation of latent Gaussian variables and systematic shape differences are modeled by Gaussian processes. To model cross-covariance between sample coordinates we introduce a class of low-dimensional cross-covariance structures suitable for modeling multivariate functional data. We present a method for doing maximum-likelihood estimation in the models and apply the method to three data sets. The first data set is from a motion tracking system where the spatial positions of a large number of body-markers are tracked in three-dimensions over time. The second data set consists of height and weight measurements for Danish boys. The third data set consists of three-dimensional spatial hand paths from a controlled obstacle-avoidance experiment. We use the developed method to estimate the cross-covariance structure, and use a classification setup to demonstrate that the method outperforms state-of-the-art methods for handling misaligned curve data.Comment: 44 pages in total including tables and figures. Additional 9 pages of supplementary material and reference

Fixed Effect Estimation of Large T Panel Data Models

This article reviews recent advances in fixed effect estimation of panel data models for long panels, where the number of time periods is relatively large. We focus on semiparametric models with unobserved individual and time effects, where the distribution of the outcome variable conditional on covariates and unobserved effects is specified parametrically, while the distribution of the unobserved effects is left unrestricted. Compared to existing reviews on long panels (Arellano and Hahn 2007; a section in Arellano and Bonhomme 2011) we discuss models with both individual and time effects, split-panel Jackknife bias corrections, unbalanced panels, distribution and quantile effects, and other extensions. Understanding and correcting the incidental parameter bias caused by the estimation of many fixed effects is our main focus, and the unifying theme is that the order of this bias is given by the simple formula p/n for all models discussed, with p the number of estimated parameters and n the total sample size.Comment: 40 pages, 1 tabl

Small sample inference for probabilistic index models

Probabilistic index models may be used to generate classical and new rank tests, with the additional advantage of supplementing them with interpretable effect size measures. The popularity of rank tests for small sample inference makes probabilistic index models also natural candidates for small sample studies. However, at present, inference for such models relies on asymptotic theory that can deliver poor approximations of the sampling distribution if the sample size is rather small. A bias-reduced version of the bootstrap and adjusted jackknife empirical likelihood are explored. It is shown that their application leads to drastic improvements in small sample inference for probabilistic index models, justifying the use of such models for reliable and informative statistical inference in small sample studies

Improving likelihood-based inference in control rate regression

Control rate regression is a diffuse approach to account for heterogeneity among studies in meta-analysis by including information about the outcome risk of patients in the control condition. Correcting for the presence of measurement error affecting risk information in the treated and in the control group has been recognized as a necessary step to derive reliable inferential conclusions. Within this framework, the paper considers the problem of small sample size as an additional source of misleading inference about the slope of the control rate regression. Likelihood procedures relying on first-order approximations are shown to be substantially inaccurate, especially when dealing with increasing heterogeneity and correlated measurement errors. We suggest to address the problem by relying on higher-order asymptotics. In particular, we derive Skovgaard's statistic as an instrument to improve the accuracy of the approximation of the signed profile log-likelihood ratio statistic to the standard normal distribution. The proposal is shown to provide much more accurate results than standard likelihood solutions, with no appreciable computational effort. The advantages of Skovgaard's statistic in control rate regression are shown in a series of simulation experiments and illustrated in a real data example. R code for applying first- and second-order statistic for inference on the slope on the control rate regression is provided

Stochastic ordinary differential equations in applied and computational mathematics

Using concrete examples, we discuss the current and potential use of stochastic ordinary differential equations (SDEs) from the perspective of applied and computational mathematics. Assuming only a minimal background knowledge in probability and stochastic processes, we focus on aspects that distinguish SDEs from their deterministic counterparts. To illustrate a multiscale modelling framework, we explain how SDEs arise naturally as diffusion limits in the type of discrete-valued stochastic models used in chemical kinetics, population dynamics, and, most topically, systems biology. We outline some key issues in existence, uniqueness and stability that arise when SDEs are used as physical models, and point out possible pitfalls. We also discuss the use of numerical methods to simulate trajectories of an SDE and explain how both weak and strong convergence properties are relevant for highly-efficient multilevel Monte Carlo simulations. We flag up what we believe to be key topics for future research, focussing especially on nonlinear models, parameter estimation, model comparison and multiscale simulation

Modeling and inference of multisubject fMRI data

Functional magnetic resonance imaging (fMRI) is a rapidly growing technique for studying the brain in action. Since its creation [1], [2], cognitive scientists have been using fMRI to understand how we remember, manipulate, and act on information in our environment. Working with magnetic resonance physicists, statisticians, and engineers, these scientists are pushing the frontiers of knowledge of how the human brain works. The design and analysis of single-subject fMRI studies has been well described. For example, [3], chapters 10 and 11 of [4], and chapters 11 and 14 of [5] all give accessible overviews of fMRI methods for one subject. In contrast, while the appropriate manner to analyze a group of subjects has been the topic of several recent papers, we do not feel it has been covered well in introductory texts and review papers. Therefore, in this article, we bring together old and new work on so-called group modeling of fMRI data using a consistent notation to make the methods more accessible and comparable