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.     

发展高新技术应处理好的六大关系

高新技术的成长发育离不开风险投资以及政府、市场的引导 ,离不开基础研究与人力资源的开发 ,更需要引进大量的资金及国外的先进技术 ,同时其发展也与传统产业的提升有着密不可分的关系 ,因此发展高新技术产业应在妥善处理好这些关系上下功夫     

论创新教育的几个辩证关系

创新教育是由多方面的辩证关系构成的复杂体系。探讨了创新教育对象的主客体二重性 ,社会化和个性化 ,创新教育的实施途径三个问题     

Bayesian analysis of directed graphs data with applications to social networks

Summary.  A fully Bayesian analysis of directed graphs, with particular emphasis on applica- tions in social networks, is explored. The model is capable of incorporating the effects of covariates, within and between block ties and multiple responses. Inference is straightforward by using software that is based on Markov chain Monte Carlo methods. Examples are provided which highlight the variety of data sets that can be entertained and the ease with which they can be analysed.     

New imperfect rankings models for ranked set sampling

Ranked set sampling is a sampling approach that leads to improved statistical inference in situations where the units to be sampled can be ranked relative to each other prior to formal measurement. This ranking may be done either by subjective judgment or according to an auxiliary variable, and it need not be completely accurate. In fact, results in the literature have shown that no matter how poor the quality of the ranking, procedures based on ranked set sampling tend to be at least as efficient as procedures based on simple random sampling. However, efforts to quantify the gains in efficiency for ranked set sampling procedures have been hampered by a shortage of available models for imperfect rankings. In this paper, we introduce a new class of models for imperfect rankings, and we provide a rigorous proof that essentially any reasonable model for imperfect rankings is a limit of models in this class. We then describe a specific, easily applied method for selecting an appropriate imperfect rankings model from the class.     

D-efficient window experimental designs

In the paper we present a new method of calculating sampling intervals, so-called windows, allowing an experimenter some flexibility in timing the sample collection, while a minimum required design efficiency for parameter estimation is assured. The method is based on the Equivalence Theorem for D-optimality what makes the length of each window related to the parameter sensitivities. An example of calculating the windows in a pharmacokinetic study is presented. Some other methods of calculating efficient sampling windows are briefly discussed.     

The evaluation of DNA evidence in pedigrees requiring population inference

Summary. The evaluation of nuclear DNA evidence for identification purposes is performed here taking account of the uncertainty about population parameters. Graphical models are used to detail the hypotheses being debated in a trial with the aim of obtaining a directed acyclic graph. Graphs also clarify the set of evidence that contributes to population inferences and they also describe the conditional independence structure of DNA evidence. Numerical illustrations are provided by re-examining three case-studies taken from the literature. Our calculations of the weight of evidence differ from those given by the authors of case-studies in that they reveal more conservative values.     

A spatiotemporal auto-regressive moving average model for solar radiation

Summary.  To investigate the variability in energy output from a network of photovoltaic cells, solar radiation was recorded at 10 sites every 10 min in the Pentland Hills to the south of Edinburgh. We identify spatiotemporal auto-regressive moving average models as the most appropriate to address this problem. Although previously considered computationally prohibitive to work with, we show that by approximating using toroidal space and fitting by matching auto-correlations, calculations can be substantially reduced. We find that a first-order spatiotemporal auto-regressive (STAR(1)) process with a first-order neighbourhood structure and a Matern noise process provide an adequate fit to the data, and we demonstrate its use in simulating realizations of energy output.     

Estimation of dependence between paired correlated failure times in the presence of covariate measurement error

Summary. In many biomedical studies, covariates are subject to measurement error. Although it is well known that the regression coefficients estimators can be substantially biased if the measurement error is not accommodated, there has been little study of the effect of covariate measurement error on the estimation of the dependence between bivariate failure times. We show that the dependence parameter estimator in the Clayton–Oakes model can be considerably biased if the measurement error in the covariate is not accommodated. In contrast with the typical bias towards the null for marginal regression coefficients, the dependence parameter can be biased in either direction. We introduce a bias reduction technique for the bivariate survival function in copula models while assuming an additive measurement error model and replicated measurement for the covariates, and we study the large and small sample properties of the dependence parameter estimator proposed.     

Conditional Likelihood Estimators for Hidden Markov Models and Stochastic Volatility Models

ABSTRACT.  This paper develops a new contrast process for parametric inference of general hidden Markov models, when the hidden chain has a non-compact state space. This contrast is based on the conditional likelihood approach, often used for ARCH-type models. We prove the strong consistency of the conditional likelihood estimators under appropriate conditions. The method is applied to the Kalman filter (for which this contrast and the exact likelihood lead to asymptotically equivalent estimators) and to the discretely observed stochastic volatility models.