半参数纵向模型的惩罚二次推断函数估计

针对纵向数据半参数模型E(y|x,t)=XTβ+f(t),采用惩罚二次推断函数方法同时估计模型中的回归参数β和未知光滑函数f(t)。首先利用截断幂函数基对未知光滑函数进行基函数展开近似,然后利用惩罚样条的思想构造关于回归参数和基函数系数的惩罚二次推断函数,最小化惩罚二次推断函数便可得到回归参数和基函数系数的惩罚二次推断函数估计。理论结果显示,估计结果具有相合性和渐近正态性,通过数值方法也得到了较好的模拟结果。     

A COMPARISON OF MIXED MODEL SPLINES FOR CURVE FITTING

Three types of polynomial mixed model splines have been proposed: smoothing splines, P‐splines and penalized splines using a truncated power function basis. The close connections between these models are demonstrated, showing that the default cubic form of the splines differs only in the penalty used. A general definition of the mixed model spline is given that includes general constraints and can be used to produce natural or periodic splines. The impact of different penalties is demonstrated by evaluation across a set of functions with specific features, and shows that the best penalty in terms of mean squared error of prediction depends on both the form of the underlying function and the signal:noise ratio.     

Thin plate regression splines

Summary. I discuss the production of low rank smoothers for d  ≥ 1 dimensional data, which can be fitted by regression or penalized regression methods. The smoothers are constructed by a simple transformation and truncation of the basis that arises from the solution of the thin plate spline smoothing problem and are optimal in the sense that the truncation is designed to result in the minimum possible perturbation of the thin plate spline smoothing problem given the dimension of the basis used to construct the smoother. By making use of Lanczos iteration the basis change and truncation are computationally efficient. The smoothers allow the use of approximate thin plate spline models with large data sets, avoid the problems that are associated with 'knot placement' that usually complicate modelling with regression splines or penalized regression splines, provide a sensible way of modelling interaction terms in generalized additive models, provide low rank approximations to generalized smoothing spline models, appropriate for use with large data sets, provide a means for incorporating smooth functions of more than one variable into non-linear models and improve the computational efficiency of penalized likelihood models incorporating thin plate splines. Given that the approach produces spline-like models with a sparse basis, it also provides a natural way of incorporating unpenalized spline-like terms in linear and generalized linear models, and these can be treated just like any other model terms from the point of view of model selection, inference and diagnostics.     

Analysis of growth curve data by using cubic smoothing splines

Longitudinal data frequently arises in various fields of applied sciences where individuals are measured according to some ordered variable, e.g. time. A common approach used to model such data is based on the mixed models for repeated measures. This model provides an eminently flexible approach to modeling of a wide range of mean and covariance structures. However, such models are forced into a rigidly defined class of mathematical formulas which may not be well supported by the data within the whole sequence of observations. A possible non-parametric alternative is a cubic smoothing spline, which is highly flexible and has useful smoothing properties. It can be shown that under normality assumption, the solution of the penalized log-likelihood equation is the cubic smoothing spline, and this solution can be further expressed as a solution of the linear mixed model. It is shown here how cubic smoothing splines can be easily used in the analysis of complete and balanced data. Analysis can be greatly simplified by using the unweighted estimator studied in the paper. It is shown that if the covariance structure of random errors belong to certain class of matrices, the unweighted estimator is the solution to the penalized log-likelihood function. This result is new in smoothing spline context and it is not only confined to growth curve settings. The connection to mixed models is used in developing a rough testing of group profiles. Numerical examples are presented to illustrate the techniques proposed.     

Inference in generalized additive mixed modelsby using smoothing splines

Generalized additive mixed models are proposed for overdispersed and correlated data, which arise frequently in studies involving clustered, hierarchical and spatial designs. This class of models allows flexible functional dependence of an outcome variable on covariates by using nonparametric regression, while accounting for correlation between observations by using random effects. We estimate nonparametric functions by using smoothing splines and jointly estimate smoothing parameters and variance components by using marginal quasi-likelihood. Because numerical integration is often required by maximizing the objective functions, double penalized quasi-likelihood is proposed to make approximate inference. Frequentist and Bayesian inferences are compared. A key feature of the method proposed is that it allows us to make systematic inference on all model components within a unified parametric mixed model framework and can be easily implemented by fitting a working generalized linear mixed model by using existing statistical software. A bias correction procedure is also proposed to improve the performance of double penalized quasi-likelihood for sparse data. We illustrate the method with an application to infectious disease data and we evaluate its performance through simulation.     

Penalized spline joint models for longitudinal and time-to-event data

The joint models for longitudinal data and time-to-event data have recently received numerous attention in clinical and epidemiologic studies. Our interest is in modeling the relationship between event time outcomes and internal time-dependent covariates. In practice, the longitudinal responses often show non linear and fluctuated curves. Therefore, the main aim of this paper is to use penalized splines with a truncated polynomial basis to parameterize the non linear longitudinal process. Then, the linear mixed-effects model is applied to subject-specific curves and to control the smoothing. The association between the dropout process and longitudinal outcomes is modeled through a proportional hazard model. Two types of baseline risk functions are considered, namely a Gompertz distribution and a piecewise constant model. The resulting models are referred to as penalized spline joint models; an extension of the standard joint models. The expectation conditional maximization (ECM) algorithm is applied to estimate the parameters in the proposed models. To validate the proposed algorithm, extensive simulation studies were implemented followed by a case study. In summary, the penalized spline joint models provide a new approach for joint models that have improved the existing standard joint models.     

A Mixed Model Approach for Geoadditive Hazard Regression

Abstract.  Mixed model based approaches for semiparametric regression have gained much interest in recent years, both in theory and application. They provide a unified and modular framework for penalized likelihood and closely related empirical Bayes inference. In this article, we develop mixed model methodology for a broad class of Cox-type hazard regression models where the usual linear predictor is generalized to a geoadditive predictor incorporating non-parametric terms for the (log-)baseline hazard rate, time-varying coefficients and non-linear effects of continuous covariates, a spatial component, and additional cluster-specific frailties. Non-linear and time-varying effects are modelled through penalized splines, while spatial components are treated as correlated random effects following either a Markov random field or a stationary Gaussian random field prior. Generalizing existing mixed model methodology, inference is derived using penalized likelihood for regression coefficients and (approximate) marginal likelihood for smoothing parameters. In a simulation we study the performance of the proposed method, in particular comparing it with its fully Bayesian counterpart using Markov chain Monte Carlo methodology, and complement the results by some asymptotic considerations. As an application, we analyse leukaemia survival data from northwest England.     

Estimation of the Force of Infection from Current Status Data Using Generalized Linear Mixed Models

Based on sero-prevalence data of rubella, mumps in the UK and varicella in Belgium, we show how the force of infection, the age-specific rate at which susceptible individuals contract infection, can be estimated using generalized linear mixed models (McCulloch & Searle, 2001). Modelling the dependency of the force of infection on age by penalized splines, which involve fixed and random effects, allows us to use generalized linear mixed models techniques to estimate both the cumulative probability of being infected before a given age and the force of infection. Moreover, these models permit an automatic selection of the smoothing parameter. The smoothness of the estimated force of infection can be influenced by the number of knots and the degree of the penalized spline used. To determine these, a different number of knots and different degrees are used and the results are compared to establish this sensitivity. Simulations with a different number of knots and polynomial spline bases of different degrees suggest - for estimating the force of infection from serological data - the use of a quadratic penalized spline based on about 10 knots.     

Smoothing spline Gaussian regression: more scalable computation via efficient approximation

Summary.  Smoothing splines via the penalized least squares method provide versatile and effective nonparametric models for regression with Gaussian responses. The computation of smoothing splines is generally of the order O ( n ³), n being the sample size, which severely limits its practical applicability. We study more scalable computation of smoothing spline regression via certain low dimensional approximations that are asymptotically as efficient. A simple algorithm is presented and the Bayes model that is associated with the approximations is derived, with the latter guiding the porting of Bayesian confidence intervals. The practical choice of the dimension of the approximating space is determined through simulation studies, and empirical comparisons of the approximations with the exact solution are presented. Also evaluated is a simple modification of the generalized cross-validation method for smoothing parameter selection, which to a large extent fixes the occasional undersmoothing problem that is suffered by generalized cross-validation.     

Fast covariance estimation for sparse functional data

Smoothing of noisy sample covariances is an important component in functional data analysis. We propose a novel covariance smoothing method based on penalized splines and associated software. The proposed method is a bivariate spline smoother that is designed for covariance smoothing and can be used for sparse functional or longitudinal data. We propose a fast algorithm for covariance smoothing using leave-one-subject-out cross-validation. Our simulations show that the proposed method compares favorably against several commonly used methods. The method is applied to a study of child growth led by one of coauthors and to a public dataset of longitudinal CD4 counts.     

Penalized Spline Estimation for Varying-Coefficient Models

Varying-coefficient models are useful extensions of classical linear models. They arise from multivariate nonparametric regression, nonlinear time series modeling and forecasting, longitudinal data analysis, and others. This article proposes the penalized spline estimation for the varying-coefficient models. Assuming a fixed but potentially large number of knots, the penalized spline estimators are shown to be strong consistency and asymptotic normality. A systematic optimization algorithm for the selection of multiple smoothing parameters is developed. One of the advantages of the penalized spline estimation is that it can accommodate varying degrees of smoothness among coefficient functions due to multiple smoothing parameters being used. Some simulation studies are presented to illustrate the proposed methods.     

Knot selection for least-squares and penalized splines

Two new stochastic search methods are proposed for optimizing the knot locations and/or smoothing parameters for least-squares or penalized splines. One of the methods is a golden-section-augmented blind search, while the other is a continuous genetic algorithm. Monte Carlo experiments indicate that the algorithms are very successful at producing knot locations and/or smoothing parameters that are near optimal in a squared error sense. Both algorithms are amenable to parallelization and have been implemented in OpenMP and MPI. An adjusted GCV criterion is also considered for selecting both the number and location of knots. The method performed well relative to MARS in a small empirical comparison.     

Mixed effects smoothing spline analysis of variance

We propose a general family of nonparametric mixed effects models. Smoothing splines are used to model the fixed effects and are estimated by maximizing the penalized likelihood function. The random effects are generic and are modelled parametrically by assuming that the covariance function depends on a parsimonious set of parameters. These parameters and the smoothing parameter are estimated simultaneously by the generalized maximum likelihood method. We derive a connection between a nonparametric mixed effects model and a linear mixed effects model. This connection suggests a way of fitting a nonparametric mixed effects model by using existing programs. The classical two-way mixed models and growth curve models are used as examples to demonstrate how to use smoothing spline analysis-of-variance decompositions to build nonparametric mixed effects models. Similarly to the classical analysis of variance, components of these nonparametric mixed effects models can be interpreted as main effects and interactions. The penalized likelihood estimates of the fixed effects in a two-way mixed model are extensions of James–Stein shrinkage estimates to correlated observations. In an example three nested nonparametric mixed effects models are fitted to a longitudinal data set.     

Reference priors for linear models with general covariance structures

We develop a new class of reference priors for linear models with general covariance structures. A general Markov chain Monte Carlo algorithm is also proposed for implementing the computation. We present several examples to demonstrate the results: Bayesian penalized spline smoothing, a Bayesian approach to bivariate smoothing for a spatial model, and prior specification for structural equation models.     

ON CONFIDENCE INTERVALS FOR GENERALIZED ADDITIVE MODELS BASED ON PENALIZED REGRESSION SPLINES

Generalized additive models represented using low rank penalized regression splines, estimated by penalized likelihood maximisation and with smoothness selected by generalized cross validation or similar criteria, provide a computationally efficient general framework for practical smooth modelling. Various authors have proposed approximate Bayesian interval estimates for such models, based on extensions of the work of Wahba, G. (1983) [Bayesian confidence intervals for the cross validated smoothing spline. J. R. Statist. Soc. B 45 , 133–150] and Silverman, B.W. (1985) [Some aspects of the spline smoothing approach to nonparametric regression curve fitting. J. R. Statist. Soc. B 47 , 1–52] on smoothing spline models of Gaussian data, but testing of such intervals has been rather limited and there is little supporting theory for the approximations used in the generalized case. This paper aims to improve this situation by providing simulation tests and obtaining asymptotic results supporting the approximations employed for the generalized case. The simulation results suggest that while across‐the‐model performance is good, component‐wise coverage probabilities are not as reliable. Since this is likely to result from the neglect of smoothing parameter variability, a simple and efficient simulation method is proposed to account for smoothing parameter uncertainty: this is demonstrated to substantially improve the performance of component‐wise intervals.     

Functional variance estimation using penalized splines with principal component analysis

In many fields of empirical research one is faced with observations arising from a functional process. If so, classical multivariate methods are often not feasible or appropriate to explore the data at hand and functional data analysis is prevailing. In this paper we present a method for joint modeling of mean and variance in longitudinal data using penalized splines. Unlike previous approaches we model both components simultaneously via rich spline bases. Estimation as well as smoothing parameter selection is carried out using a mixed model framework. The resulting smooth covariance structures are then used to perform principal component analysis. We illustrate our approach by several simulations and an application to financial interest data.     

Some asymptotic results on generalized penalized spline smoothing

Summary.  The paper discusses asymptotic properties of penalized spline smoothing if the spline basis increases with the sample size. The proof is provided in a generalized smoothing model allowing for non-normal responses. The results are extended in two ways. First, assuming the spline coefficients to be a priori normally distributed links the smoothing framework to generalized linear mixed models. We consider the asymptotic rates such that the Laplace approximation is justified and the resulting fits in the mixed model correspond to penalized spline estimates. Secondly, we make use of a fully Bayesian viewpoint by imposing an a priori distribution on all parameters and coefficients. We argue that with the postulated rates at which the spline basis dimension increases with the sample size the posterior distribution of the spline coefficients is approximately normal. The validity of this result is investigated in finite samples by comparing Markov chain Monte Carlo results with their asymptotic approximation in a simulation study.     

Estimating curves and derivatives with parametric penalized spline smoothing

Accurate estimation of an underlying function and its derivatives is one of the central problems in statistics. Parametric forms are often proposed based on the expert opinion or prior knowledge of the underlying function. However, these strict parametric assumptions may result in biased estimates when they are not completely accurate. Meanwhile, nonparametric smoothing methods, which do not impose any parametric form, are quite flexible. We propose a parametric penalized spline smoothing method, which has the same flexibility as the nonparametric smoothing methods. It also uses the prior knowledge of the underlying function by defining an additional penalty term using the distance of the fitted function to the assumed parametric function. Our simulation studies show that the parametric penalized spline smoothing method can obtain more accurate estimates of the function and its derivatives than the penalized spline smoothing method. The parametric penalized spline smoothing method is also demonstrated by estimating the human height function and its derivatives from the real data.     

MODEL SELECTION FOR PENALIZED SPLINE SMOOTHING USING AKAIKE INFORMATION CRITERIA

Two different forms of Akaike's information criterion (AIC) are compared for selecting the smooth terms in penalized spline additive mixed models. The conditional AIC (cAIC) has been used traditionally as a criterion for both estimating penalty parameters and selecting covariates in smoothing, and is based on the conditional likelihood given the smooth mean and on the effective degrees of freedom for a model fit. By comparison, the marginal AIC (mAIC) is based on the marginal likelihood from the mixed‐model formulation of penalized splines which has recently become popular for estimating smoothing parameters. To the best of the authors' knowledge, the use of mAIC for selecting covariates for smoothing in additive models is new. In the competing models considered for selection, covariates may have a nonlinear effect on the response, with the possibility of group‐specific curves. Simulations are used to compare the performance of cAIC and mAIC in model selection settings that have correlated and hierarchical smooth terms. In moderately large samples, both formulations of AIC perform extremely well at detecting the function that generated the data. The mAIC does better for simple functions, whereas the cAIC is more sensitive to detecting a true model that has complex and hierarchical terms.