Constructing optimal designs for fitting pharmacokinetic models

We consider some computational issues that arise when searching for optimal designs for pharmacokinetic (PK) studies. Special factors that distinguish these are (i) repeated observations are taken from each subject and the observations are usually described by a nonlinear mixed model (NLMM), (ii) design criteria depend on the model fitting procedure, (iii) in addition to providing efficient parameter estimates, the design must also permit model checking, (iv) in practice there are several design constraints, (v) the design criteria are computationally expensive to evaluate and often numerical integration is needed and finally (vi) local optimisation procedures may fail to converge or get trapped at local optima.We review current optimal design algorithms and explore the possibility of using global optimisation procedures. We use these latter procedures to find some optimal designs.For multi-purpose designs we suggest two surrogate design criteria for model checking and illustrate their use.     

A New Model of Trend Inflation

This article introduces a new model of trend inflation. In contrast to many earlier approaches, which allow for trend inflation to evolve according to a random walk, ours is a bounded model which ensures that trend inflation is constrained to lie in an interval. The bounds of this interval can either be fixed or estimated from the data. Our model also allows for a time-varying degree of persistence in the transitory component of inflation. In an empirical exercise with CPI inflation, we find the model to work well, yielding more sensible measures of trend inflation and forecasting better than popular alternatives such as the unobserved components stochastic volatility model. This article has supplementary materials online.     

Inference Under Right Censoring in a Discrete Setup

In this article, we consider the right random censoring scheme in a discrete setup when the lifetime and censoring variables are independent and have geometric distributions with means 1/θ₁ and 1/θ₂, respectively. We first obtain the Maximum Likelihood and Method of Moment estimators of the unknown parameters. We also find the Bayes and Posterior Regret Gamma Minimax estimators of the parameters for the two cases when the prior distributions are dependent and independent, assuming a squared error loss function. We then discuss the Proportional Hazard model, and obtain Maximum Likelihood estimators of the unknown parameters and derive the Bayes estimators assuming squared error loss using Markov Chain Monte Carlo methods.     

Additive Transformation Models for Recurrent Events

In this article, we propose a class of additive transformation models for recurrent event data, which includes the additive rates model as a special case. The new models offer great flexibility in formulating the effects of covariates on the mean function of recurrent events. Estimating equation approaches are developed for the model parameters, and asymptotic properties of the resulting estimators are established. In addition, a model checking procedure is presented to assess the adequacy of the model. The finite sample performance of the proposed estimators is examined through simulation studies, and an application to a bladder cancer study is presented.     

Modeling Endogenous Mobility in Earnings Determination

ABSTRACT

We evaluate the bias from endogenous job mobility in fixed-effects estimates of worker- and firm-specific earnings heterogeneity using longitudinally linked employer–employee data from the LEHD infrastructure file system of the U.S. Census Bureau. First, we propose two new residual diagnostic tests of the assumption that mobility is exogenous to unmodeled determinants of earnings. Both tests reject exogenous mobility. We relax exogenous mobility by modeling the matched data as an evolving bipartite graph using a Bayesian latent-type framework. Our results suggest that allowing endogenous mobility increases the variation in earnings explained by individual heterogeneity and reduces the proportion due to employer and match effects. To assess external validity, we match our estimates of the wage components to out-of-sample estimates of revenue per worker. The mobility-bias-corrected estimates attribute much more of the variation in revenue per worker to variation in match quality and worker quality than the uncorrected estimates. Supplementary materials for this article are available online.     

A note on connectedness in fixed effects manova and gmanova models withmissing cells

Murray and Smith (1985) and Hocking (1985) give a generalized definition and test of connectedness in the case of missing cells using the univariate cell-means model with linear restrictions on the cell-means. The test of connectedness is here extended to multivariate fixed effects models, including the usual MANOVA model with linear restrictions, the MANOVA model with double linear restrictions, and the GMANOVA model.     

A Conditional Variance Model for Daily Deviations of an Exchange Rate

A model for the distribution of daily deviations of an exchange rate is suggested. The distribution is Gaussian with a variance that depends on previous deviations. The model is applied to the exchange rate of the U.S. dollar to special drawing rights.     

Goodness-of-Fit Tests for Multiplicative Models with Dependent Data

Abstract.  Several classical time series models can be written as a regression model between the components of a strictly stationary bivariate process. Some of those models, such as the ARCH models, share the property of proportionality of the regression function and the scale function, which is an interesting feature in econometric and financial models. In this article, we present a procedure to test for this feature in a non-parametric context. The test is based on the difference between two non-parametric estimators of the distribution of the regression error. Asymptotic results are proved and some simulations are shown in the paper in order to illustrate the finite sample properties of the procedure.     

A note on the equality of the OLSE and the BLUE of the parametric function in the general Gauss–Markov model

In this note we consider the equality of the ordinary least squares estimator (OLSE) and the best linear unbiased estimator (BLUE) of the estimable parametric function in the general Gauss–Markov model. Especially we consider the structures of the covariance matrix V for which the OLSE equals the BLUE. Our results are based on the properties of a particular reparametrized version of the original Gauss–Markov model.      

On cumulative entropies

In analogy with the cumulative residual entropy recently proposed by Wang et al. [2003a. A new and robust information theoretic measure and its application to image alignment. In: Information Processing in Medical Imaging. Lecture Notes in Computer Science, vol. 2732, Springer, Heidelberg, pp. 388–400; 2003b. Cumulative residual entropy, a new measure of information and its application to image alignment. In: Proceedings on the Ninth IEEE International Conference on Computer Vision (ICCV’03), vol. 1, IEEE Computer Society Press, Silver Spring, MD, pp. 548–553], we introduce and study the cumulative entropy, which is a new measure of information alternative to the classical differential entropy. We show that the cumulative entropy of a random lifetime X can be expressed as the expectation of its mean inactivity time evaluated at X. Hence, our measure is particularly suitable to describe the information in problems related to ageing properties of reliability theory based on the past and on the inactivity times. Our results include various bounds to the cumulative entropy, its connection to the proportional reversed hazards model, and the study of its dynamic version that is shown to be increasing if the mean inactivity time is increasing. The empirical cumulative entropy is finally proposed to estimate the new information measure.