Extended Poisson process modelling of dilution series data

Summary.  Data comprising colony counts, or a binary variable representing fertile (or sterile) samples, as a dilution series of the containing medium are analysed by using extended Poisson process modelling. These models form a class of flexible probability distributions that are widely applicable to count and grouped binary data. Standard distributions such as Poisson and binomial, and those representing overdispersion and underdispersion relative to these distributions can be expressed within this class. For all the models in the class, likelihoods can be obtained. These models have not been widely used because of the perceived difficulty of performing the calculations and the lack of associated software. Exact calculation of the probabilities that are involved can be time consuming although accurate approximations that use considerably less computational time are available. Although dilution series data are the focus here, the models are applicable to any count or binary data. A benefit of the approach is the ability to draw likelihood-based inferences from the data.     

Accounting for uncertainty in extremal dependence modeling using Bayesian model averaging techniques

Modeling the joint tail of an unknown multivariate distribution can be characterized as modeling the tail of each marginal distribution and modeling the dependence structure between the margins. Classical methods for modeling multivariate extremes are based on the class of multivariate extreme value distributions. However, such distributions do not allow for the possibility of dependence at finite levels that vanishes in the limit. Alternative models have been developed that account for this asymptotic independence, but inferential statistical procedures seeking to combine the classes of asymptotically dependent and asymptotically independent models have been of limited use. We overcome these difficulties by employing Bayesian model averaging to account for both types of asymptotic behavior, and for subclasses within the asymptotically independent framework. Our approach also allows for the calculation of posterior probabilities of different classes of models, allowing for direct comparison between them. We demonstrate the use of joint tail models based on our broader methodology using two oceanographic datasets and a brief simulation study.     

Estimating numbers of infectious units from serial dilution assays

Summary.  The paper concerns the design and analysis of serial dilution assays to estimate the infectivity of a sample of tissue when it is assumed that the sample contains a finite number of indivisible infectious units such that a subsample will be infectious if it contains one or more of these units. The aim of the study is to estimate the number of infectious units in the original sample. The standard approach to the analysis of data from such a study is based on the assumption of independence of aliquots both at the same dilution level and at different dilution levels, so that the numbers of infectious units in the aliquots follow independent Poisson distributions. An alternative approach is based on calculation of the expected value of the total number of samples tested that are not infectious. We derive the likelihood for the data on the basis of the discrete number of infectious units, enabling calculation of the maximum likelihood estimate and likelihood-based confidence intervals. We use the exact probabilities that are obtained to compare the maximum likelihood estimate with those given by the other methods in terms of bias and standard error and to compare the coverage of the confidence intervals. We show that the methods have very similar properties and conclude that for practical use the method that is based on the Poisson assumption is to be recommended, since it can be implemented by using standard statistical software. Finally we consider the design of serial dilution assays, concluding that it is important that neither the dilution factor nor the number of samples that remain untested should be too large.     

进口需求函数选择及弹性分析——以美国苹果汁进口需求为例

运用2002年1月至2010年12月间,共108组美国苹果汁进口月度数据,比较分析Barten（1993）发展的一般化需求模型与其交错的四种可微分的需求模型,探寻和检验适合美国苹果汁进口需求数据资料的模型形式;对模型的加总性、齐次性、对称性、自变量内生性、需求系统的拟合优度进行检验,结果显示：一般化需求模型更符合数据资料。美国对中国苹果汁进口需求的支出弹性显著为正;受中国苹果汁自价格影响不显著;中国苹果汁对美出口的主要竞争国家是加拿大。     

Parameter estimates and tests of fit for infinite mixther distrirutions

Al though mixtures form a rich class of probability models, they often present difficulties for statistical inference. Likelihood functions are sometimes unbounded at certain values of the parameters, and densities often have no closed form. These features complicate hoth maximum-likelihood estimation and tests of fit based on the empirical distribution function. New inferential methods using sample characteristic functions (Cfs) and moment generating functions (MGFs) seem well-suited to mixtures. since these transforms often take simple form/ This paper reports a simulation study of the properties of estimators and tests of fit based on CFs, MGFs, and sample moments when applied to three specific families of thick tailed mixture distributios.     

Semiparametric Efficient Estimation for a Class of Generalized Proportional Odds Cure Models

We present a mixture cure model with the survival time of the "uncured" group coming from a class of linear transformation models, which is an extension of the proportional odds model. This class of model, first proposed by Dabrowska and Doksum (1988), which we term "generalized proportional odds model," is well suited for the mixture cure model setting due to a clear separation between long-term and short-term effects. A standard expectation-maximization algorithm can be employed to locate the nonparametric maximum likelihood estimators, which are shown to be consistent and semiparametric efficient. However, there are difficulties in the M-step due to the nonparametric component. We overcome these difficulties by proposing two different algorithms. The first is to employ an majorize-minimize (MM) algorithm in the M-step instead of the usual Newton-Raphson method, and the other is based on an alternative form to express the model as a proportional hazards frailty model. The two new algorithms are compared in a simulation study with an existing estimating equation approach by Lu and Ying (2004). The MM algorithm provides both computational stability and efficiency. A case study of leukemia data is conducted to illustrate the proposed procedures.     

A Comparison of Bayes Factors for Separated Models: Some Simulation Results

Some alternative Bayes Factors: Intrinsic, Posterior, and Fractional have been proposed to overcome the difficulties presented when prior information is weak and improper prior are used. Additional difficulties also appear when the models are separated or non nested. This article presents both simulation results and some illustrative examples analysis comparing these alternative Bayes factors to discriminate among the Lognormal, the Weibull, the Gamma, and the Exponential distributions. Simulation results are obtained for different sample sizes generated from the distributions. Results from simulations indicates that these alternative Bayes factors are useful for comparing non nested models. The simulations also show some similar behavior and that when both models are true they choose the simplest model. Some illustrative example are also presented.     

Robust estimation for order of hidden Markov models based on density power divergences

In this paper, we study the robust estimation for the order of hidden Markov model (HMM) based on a penalized minimum density power divergence estimator, which is obtained by utilizing the finite mixture marginal distribution of HMM. For this task, we adopt the locally conic parametrization method used in [D. Dacunha-Castelle and E. Gassiate, Testing in locally conic models and application to mixture models. ESAIM Probab. Stat. (1997), pp. 285–317; D. Dacunha-Castelle and E. Gassiate, Testing the order of a model using locally conic parametrization: population mixtures and stationary arma processes, Ann. Statist. 27 (1999), pp. 1178–1209; T. Lee and S. Lee, Robust and consistent estimation of the order of finite mixture models based on the minimizing a density power divergence estimator, Metrika 68 (2008), pp. 365–390] to avoid the difficulties that arise in handling mixture marginal models, such as the non-identifiability of the parameter space and the singularity problem with the asymptotic variance. We verify that the estimated order is consistent and simulation results are provided for illustration.     

Markov Chain Monte Carlo Methods for Fitting Spatiotemporal Stochastic Models in Plant Epidemiology

Strategies for controlling plant epidemics are investigated by fitting continuous time spatiotemporal stochastic models to data consisting of maps of disease incidence observed at discrete times. Markov chain Monte Carlo methods are used for fitting two such models to data describing the spread of citrus tristeza virus (CTV) in an orchard. The approach overcomes some of the difficulties encountered when fitting stochastic models to infrequent observations of a continuous process. The results of the analysis cast doubt on the effectiveness of a strategy identified from a previous spatial analysis of the CTV data. Extensions of the approaches to more general models and other problems are also considered.     

Objective Testing Procedures in Linear Models: Calibration of the p-values

Abstract.  An optimal Bayesian decision procedure for testing hypothesis in normal linear models based on intrinsic model posterior probabilities is considered. It is proven that these posterior probabilities are simple functions of the classical F -statistic, thus the evaluation of the procedure can be carried out analytically through the frequentist analysis of the posterior probability of the null. An asymptotic analysis proves that, under mild conditions on the design matrix, the procedure is consistent. For any testing hypothesis it is also seen that there is a one-to-one mapping – which we call calibration curve – between the posterior probability of the null hypothesis and the classical bi p -value. This curve adds substantial knowledge about the possible discrepancies between the Bayesian and the p -value measures of evidence for testing hypothesis. It permits a better understanding of the serious difficulties that are encountered in linear models for interpreting the p -values. A specific illustration of the variable selection problem is given.     

Reliability modeling of systems with two dependent degrading components based on gamma processes

Abstract

Many engineering systems have multiple components with more than one degradation measure which is dependent on each other due to their complex failure mechanisms, which results in some insurmountable difficulties for reliability work in engineering. To overcome these difficulties, the system reliability prediction approaches based on performance degradation theory develop rapidly in recent years, and show their superiority over the traditional approaches in many applications. This paper proposes reliability models of systems with two dependent degrading components. It is assumed that the degradation paths of the components are governed by gamma processes. For a parallel system, its failure probability function can be approximated by the bivariate Birnbaum–Saunders distribution. According to the relationship of parallel and series systems, it is easy to find that the failure probability function of a series system can be expressed by the bivariate Birnbaum–Saunders distribution and its marginal distributions. The model in such a situation is very complicated and analytically intractable, and becomes cumbersome from a computational viewpoint. For this reason, the Bayesian Markov chain Monte Carlo method is developed for this problem that allows the maximum likelihood estimates of the parameters to be determined in an efficient manner. After that, the confidence intervals of the failure probability of systems are given. For an illustration of the proposed model, a numerical example about railway track is presented.     

Bayesian emulation of complex multi-output and dynamic computer models

Computer models are widely used in scientific research to study and predict the behaviour of complex systems. The run times of computer-intensive simulators are often such that it is impractical to make the thousands of model runs that are conventionally required for sensitivity analysis, uncertainty analysis or calibration. In response to this problem, highly efficient techniques have recently been developed based on a statistical meta-model (the emulator) that is built to approximate the computer model. The approach, however, is less straightforward for dynamic simulators, designed to represent time-evolving systems. Generalisations of the established methodology to allow for dynamic emulation are here proposed and contrasted. Advantages and difficulties are discussed and illustrated with an application to the Sheffield Dynamic Global Vegetation Model, developed within the UK Centre for Terrestrial Carbon Dynamics.     

Inference in model-based cluster analysis

A new approach to cluster analysis has been introduced based on parsimonious geometric modelling of the within-group covariance matrices in a mixture of multivariate normal distributions, using hierarchical agglomeration and iterative relocation. It works well and is widely used via the MCLUST software available in S-PLUS and StatLib. However, it has several limitations: there is no assessment of the uncertainty about the classification, the partition can be suboptimal, parameter estimates are biased, the shape matrix has to be specified by the user, prior group probabilities are assumed to be equal, the method for choosing the number of groups is based on a crude approximation, and no formal way of choosing between the various possible models is included. Here, we propose a new approach which overcomes all these difficulties. It consists of exact Bayesian inference via Gibbs sampling, and the calculation of Bayes factors (for choosing the model and the number of groups) from the output using the Laplace–Metropolis estimator. It works well in several real and simulated examples.     

Threshold‐free estimation of functional antibody titers of a group B streptococcus opsonophagocytic killing assay

Opsonophagocytic killing assays (OPKA) are routinely used for the quantification of bactericidal antibodies in blood serum samples. Quantification of the OPKA readout, the titer, provides the basis for the statistical analysis of vaccine clinical trials having functional immune response endpoints. Traditional OPKA titers are defined as the maximum serum dilution yielding a predefined bacterial killing threshold value, and they are estimated by fitting a dose‐response model to the dilution‐killing curve. This paper illustrates a novel definition of titer, the threshold‐free titer, which preserves biological interpretability while not depending on any killing threshold or on a postulated shape of the dose‐response curve. These titers are shown to be more precise than the traditional threshold‐based titers when using simulated and experimental group B streptococcus OPKA experimental data. Also, titer linearity is shown to be not measurable when using threshold‐based titers, whereas it becomes measurable using threshold‐free titers. The biological interpretability and operational characteristics demonstrated here indicate that threshold‐free titers are an appropriate tool for the routine analysis of OPKA data. Copyright © 2015 John Wiley & Sons, Ltd.     

Panel—Data下Granger因果检验的理论和应用发展综述

Panel-Data下Granger因果检验的相关理论是最近几年才发展起来的,现有的研究提出了关于Panel-Data下Granger因果检验的四个基本假设:同质无因果关系假设(HNCH)、同质因果关系假设(HCH)、异质因果关系假设(HECH)以及异质无因果关系假设(HENCH),根据检验参数的特点给出三种类型的检验模型:固定系数模型、随机系数模型和混合固定随机系数模型。目前,还只有固定系数模型的相关理论较为完善,另外两种模型的检验还都存在一定的难度。因此,只有从理论研究和实际应用两个方面对该理论进行阐述,并对现有的理论进行简要的评述,才可指出其存在的不足及可能的改进方向。     

Some subjective bayesian considerations in the selection of models

Some considerations relating to the post-data selection of models are discussed. These include some difficulties with orthodox theory, implementation of the likelihood principle, and Bayesian tests of hypotheses.     

Functional analysis of high-content high-throughput imaging data

High-content automated imaging platforms allow the multiplexing of several targets simultaneously to generate multi-parametric single-cell data sets over extended periods of time. Typically, standard simple measures such as mean value of all cells at every time point are calculated to summarize the temporal process, resulting in loss of time dynamics of the single cells. Multiple experiments are performed but observation time points are not necessarily identical, leading to difficulties when integrating summary measures from different experiments. We used functional data analysis to analyze continuous curve data, where the temporal process of a response variable for each single cell can be described using a smooth curve. This allows analyses to be performed on continuous functions, rather than on original discrete data points. Functional regression models were applied to determine common temporal characteristics of a set of single cell curves and random effects were employed in the models to explain variation between experiments. The aim of the multiplexing approach is to simultaneously analyze the effect of a large number of compounds in comparison to control to discriminate between their mode of action. Functional principal component analysis based on T-statistic curves for pairwise comparison to control was used to study time-dependent compound effects.     

Hyper Inverse Wishart Distribution for Non-decomposable Graphs and its Application to Bayesian Inference for Gaussian Graphical Models

While conjugate Bayesian inference in decomposable Gaussian graphical models is largely solved, the non-decomposable case still poses difficulties concerned with the specification of suitable priors and the evaluation of normalizing constants. In this paper we derive the DY-conjugate prior ( Diaconis & Ylvisaker, 1979 ) for non-decomposable models and show that it can be regarded as a generalization to an arbitrary graph G of the hyper inverse Wishart distribution ( Dawid & Lauritzen, 1993 ). In particular, if G is an incomplete prime graph it constitutes a non-trivial generalization of the inverse Wishart distribution. Inference based on marginal likelihood requires the evaluation of a normalizing constant and we propose an importance sampling algorithm for its computation. Examples of structural learning involving non-decomposable models are given. In order to deal efficiently with the set of all positive definite matrices with non-decomposable zero-pattern we introduce the operation of triangular completion of an incomplete triangular matrix. Such a device turns out to be extremely useful both in the proof of theoretical results and in the implementation of the Monte Carlo procedure.     

How to compare interpretatively different models for the conditional variance function

This study considers regression-type models with heteroscedastic Gaussian errors. The conditional variance is assumed to depend on the explanatory variables via a parametric or non-parametric variance function. The variance function has usually been selected on the basis of the log-likelihoods of fitted models. However, log-likelihood is a difficult quantity to interpret – the practical importance of differences in log-likelihoods has been difficult to assess. This study overcomes these difficulties by transforming the difference in log-likelihood to easily interpretative difference in the error of predicted deviation. In addition, methods for testing the statistical significance of the observed difference in test data log-likelihood are proposed.     

PARAMETER ESTIMATION FOR LOW-ORDER AUTO-REGRESSIVE MODELS WITH MISSING VALUES

Longitudinal data analysis in epidemiological settings is complicated by large multiplicities of short time series and the occurrence of missing observations. To handle such difficulties Rosner & Muñoz (1988) developed a weighted non-linear least squares algorithm for estimating parameters for first-order autoregressive (AR1) processes with time-varying covariates. This method proved efficient when compared to complete case procedures. Here that work is extended by (1) introducing a different estimation procedure based on the EM algorithm, and (2) formulating estimation techniques for second-order autoregressive models. The second development is important because some of the intended areas of application (adult pulmonary function decline, childhood blood pressure) have autocorrelation functions which decay more slowly than the geometric rate imposed by an AR1 model. Simulation studies are used to compare the three methodologies (non-linear, EM based and complete case) with respect to bias, efficiency and coverage both in the presence and in the absence of time-varying covariates. Differing degrees and mechanisms of missingness are examined. Preliminary results indicate the non-linear approach to be the method of choice: it has high efficiency and is easily implemented. An illustrative example concerning pulmonary function decline in the Netherlands is analyzed using this method.