Estimation of noncentrality parameters

We propose some estimators of noncentrality parameters which improve upon usual unbiased estimators under quadratic loss. The distributions we consider are the noncentral chi-square and the noncentral F. However, we give more general results for the family of elliptically contoured distributions and propose a robust dominating estimator.     

Estimation of Metabolic Rate Constants in PBPK‐Models from Liver Slice Experiments: What Are the Experimental Needs?

A mechanistic model is presented describing the clearance of a compound in a precision-cut liver slice that is incubated in a culture medium. The problem of estimating metabolic rate constants in PBPK models from liver slice experiments is discussed using identifiability analysis. From the identifiability problem analysis, it appears that in addition to the clearance, the compound's free fraction in the slice and the diffusion rate of the exchange of the compound between culture medium and liver slice should be identified. In addition, knowledge of the culture medium volume, the slice volume, the compound's free fraction, and octanol-water-based partition between medium and slice is presupposed. The formal solution for identification is discussed from the perspective of experimental practice. A formally necessary condition for identification is the sampling of parent compound in liver slice or culture medium. However, due to experimental limitations and errors, sampling the parent compound in the slice together with additional sampling of metabolite pooled from the medium and the slice is required for identification in practice. Moreover, it appears that identification results are unreliable when the value of the intrinsic clearance exceeds the value of the diffusion coefficient, a condition to be verified a posteriori.     

Physiologically Based Liver Modeling and Risk Assessment

Because of the inherent complexity of biological systems, there is often a choice between a number of apparently equally applicable physiologically based models to describe uptake and metabolism processes in toxicology or risk assessment. These models may fit the particular data sets of interest equally well, but may give quite different parameter estimates or predictions under different (extrapolated) conditions. Such competing models can be discriminated by a number of methods, including potential refutation by means of strategic experiments, and their ability to suitably incorporate all relevant physiological processes. For illustration, three currently used models for steady-state hepatic elimination--the venous equilibration model, the parallel tube model, and the distributed sinusoidal perfusion model--are reviewed and compared with particular reference to their application in the area of risk assessment. The ability of each of the models to describe and incorporate such physiological processes as protein binding, precursor-metabolite relations and hepatic zones of elimination, capillary recruitment, capillary heterogeneity, and intrahepatic shunting is discussed. Differences between the models in hepatic parameter estimation, extrapolation to different conditions, and interspecies scaling are discussed, and criteria for choosing one model over the others are presented. In this case, the distributed model provides the most general framework for describing physiological processes taking place in the liver, and has so far not been experimentally refuted, as have the other two models. These simpler models may, however, provide useful bounds on parameter estimates and on extrapolations and risk assessments.     

A simple,automatic and adaptive bivariate density estimator based on conditional densities

The standard approach to non-parametric bivariate density estimation is to use a kernel density estimator. Practical performance of this estimator is hindered by the fact that the estimator is not adaptive (in the sense that the level of smoothing is not sensitive to local properties of the density). In this paper a simple, automatic and adaptive bivariate density estimator is proposed based on the estimation of marginal and conditional densities. Asymptotic properties of the estimator are examined, and guidance to practical application of the method is given. Application to two examples illustrates the usefulness of the estimator as an exploratory tool, particularly in situations where the local behaviour of the density varies widely. The proposed estimator is also appropriate for use as a pilot estimate for an adaptive kernel estimate, since it is relatively inexpensive to calculate.     

Estimation of the parameters of symmetric stable ARMA and ARMA–GARCH models

In this article, we first propose the modified Hannan–Rissanen Method for estimating the parameters of autoregressive moving average (ARMA) process with symmetric stable noise and symmetric stable generalized autoregressive conditional heteroskedastic (GARCH) noise. Next, we propose the modified empirical characteristic function method for the estimation of GARCH parameters with symmetric stable noise. Further, we show the efficiency, accuracy and simplicity of our methods with Monte-Carlo simulation. Finally, we apply our proposed methods to model the financial data.     

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.     

Modelling Variability in the Branching Structure of Strawberry Inflorescences

The branching structure of inflorescences of the cultivated strawberry ( Fragaria × ananassa Duch.) is very variable. This paper demonstrates that some aspects of this variability are well described by a simple stochastic model of branching that has two adjustable parameters. The model is shown to provide a good fit to data from a set of almost 700 inflorescences of the cultivar Elsanta, collected over two successive years. For one parameter the maximum likelihood estimator is a moment estimator which is fully efficient even if the detailed branching structure of the inflorescences is not recorded. This parameter provides a convenient summary of branching vigour. The maximum likelihood estimator of the second parameter must be determined iteratively and can be quite inefficient unless the full branching structure is recorded. The model demonstrates that branching structure is affected by the order in which inflorescences emerge on the plant.     

Detecting a changed segment in DNA sequences

Non-coding deoxyribonucleic acid (DNA) can typically be modelled by a sequence of Bernoulli random variables by coding one base, e.g. T, as 1 and other bases as 0. If a segment of a sequence is functionally important, the probability of a 1 will be different in this changed segment from that in the surrounding DNA. It is important to be able to see whether such a segment occurs in a particular DNA sequence and to pin-point it so that a molecular biologist can investigate its possible function. Here we discuss methods for testing the occurrence of such a changed segment and how to estimate the end points of it. Maximum-likelihood-based methods are not very tractable and so a nonparametric method based on the approach of Pettitt has been developed. The problem and its solution are illustrated by a specific DNA example.     

Multiple roots of estimating functions

Estimating functions can have multiple roots. In such cases, the statistician must choose among the roots to estimate the parameter. Standard asymptotic theory shows that in a wide variety of cases, there exists a unique consistent root, and that this root will lie asymptotically close to other consistent (possibly inefficient) estimators for the parameter. For this reason, attention has largely focused on the problem of selecting this root and determining its approximate asymptotic distribution. In this paper, however, we concentrate on the exact distribution of the roots as a random set. In particular, we propose the use of higher-order root intensity functions as a tool for examining the properties of the roots and determining their most problematic features. The use of root intensity functions of first and second order is illustrated by application to the score function for the Cauchy location model.     

伽马分布的形状参数的一种估计

本文利用服从伽马分布的随机变量 X 与其逆 X~(-1)的协方差只与形状参数有关这一性质,给出伽马分布形状参数的所谓自逆协方差估计,进而构造了相应的无偏估计,并证明了这类估计的大样本性质:强相合性以及渐近正态性。