Nonlinear poisson equation for heterogeneous media

The Poisson equation is a widely accepted model for electrostatic analysis. However, the Poisson equation is derived based on electric polarizations in a linear, isotropic, and homogeneous dielectric medium. This article introduces a nonlinear Poisson equation to take into consideration of hyperpolarization effects due to intensive charges and possible nonlinear, anisotropic, and heterogeneous media. Variational principle is utilized to derive the nonlinear Poisson model from an electrostatic energy functional. To apply the proposed nonlinear Poisson equation for the solvation analysis, we also construct a nonpolar solvation energy functional based on the nonlinear Poisson equation by using the geometric measure theory. At a fixed temperature, the proposed nonlinear Poisson theory is extensively validated by the electrostatic analysis of the Kirkwood model and a set of 20 proteins, and the solvation analysis of a set of 17 small molecules whose experimental measurements are also available for a comparison. Moreover, the nonlinear Poisson equation is further applied to the solvation analysis of 21 compounds at different temperatures. Numerical results are compared to theoretical prediction, experimental measurements, and those obtained from other theoretical methods in the literature. A good agreement between our results and experimental data as well as theoretical results suggests that the proposed nonlinear Poisson model is a potentially useful model for electrostatic analysis involving hyperpolarization effects.     

Quasi Likelihood/Moment Method for Generalized and Restricted Generalized Poisson Regression Models and Its Application

This paper reviews the generalized Poisson regression model, the restricted generalized Poisson regression model and the mixed Poisson regression (negative binomial regression and Poisson inverse Gaussian regression) models which can be used for regression analysis of counts. The aim of this study is to demonstrate the quasi likelihood/moment method, which is used for estimation of the parameters of mixed Poisson regression models, also applicable to obtain the estimates of the parameters of the generalized Poisson regression and the restricted generalized Poisson regression models. Besides, at the end of this study an application related to this method for zoological data is given.     

Graphical representation of a generalized linear model-based statistical test estimating the fit of the single-hit Poisson model to limiting dilution assays.

Standardized statistical and graphical methods for analysis of limiting dilution assays are highly desirable to enable investigators to compare and interpret results and conclusions with greater accuracy and precision. According to these requirements, we present in this work a powerful statistical slope test that estimates the fit of the single-hit Poisson model to limiting dilution experiments. This method is readily amenable to a graphical representation. This slope test is obtained by modeling limiting dilution data according to a linear log-log regression model, which is a generalized linear model specially designed for modeling binary data. The result of the statistical slope test can then be graphed to visualize whether the data are compatible or not with the single-hit Poisson model. We demonstrate this statistical test and its graphical representation by using two examples: a real limiting dilution experiment evaluating the growth frequency of IL-2-responsive tumor-infiltrating T cells in a malignant lymph node involved by a B cell non-Hodgkin's lymphoma, and a simulation of a limiting dilution assay corresponding to a theoretical non-single-hit Poisson model, suppressor two-target Poisson model.     

A two-state Markov mixture model for a time series of epileptic seizure counts.

This paper discusses a model for a time series of epileptic seizure counts in which the mean of a Poisson distribution changes according to an underlying two-state Markov chain. The EM algorithm (Dempster, Laird, and Rubin, 1977, Journal of the Royal Statistical Society, Series B 39, 1-38) is used to compute maximum likelihood estimators for the parameters of this two-state mixture model and extensions are made allowing for nonstationarity. The model is illustrated using daily seizure counts for patients with intractable epilepsy and results are compared with a simple Poisson distribution and Poisson regressions. Some simulation results are also presented to demonstrate the feasibility of this model.     

Analysis of Longitudinal Data of Epileptic Seizure Counts – A Two‐State Hidden Markov Regression Approach

This paper discusses a two‐state hidden Markov Poisson regression (MPR) model for analyzing longitudinal data of epileptic seizure counts, which allows for the rate of the Poisson process to depend on covariates through an exponential link function and to change according to the states of a two‐state Markov chain with its transition probabilities associated with covariates through a logit link function. This paper also considers a two‐state hidden Markov negative binomial regression (MNBR) model, as an alternative, by using the negative binomial instead of Poisson distribution in the proposed MPR model when there exists extra‐Poisson variation conditional on the states of the Markov chain. The two proposed models in this paper relax the stationary requirement of the Markov chain, allow for overdispersion relative to the usual Poisson regression model and for correlation between repeated observations. The proposed methodology provides a plausible analysis for the longitudinal data of epileptic seizure counts, and the MNBR model fits the data much better than the MPR model. Maximum likelihood estimation using the EM and quasi‐Newton algorithms is discussed. A Monte Carlo study for the proposed MPR model investigates the reliability of the estimation method, the choice of probabilities for the initial states of the Markov chain, and some finite sample behaviors of the maximum likelihood estimates, suggesting that (1) the estimation method is accurate and reliable as long as the total number of observations is reasonably large, and (2) the choice of probabilities for the initial states of the Markov process has little impact on the parameter estimates.     

Testing approaches for overdispersion in poisson regression versus the generalized poisson model

Overdispersion is a common phenomenon in Poisson modeling, and the negative binomial (NB) model is frequently used to account for overdispersion. Testing approaches (Wald test, likelihood ratio test (LRT), and score test) for overdispersion in the Poisson regression versus the NB model are available. Because the generalized Poisson (GP) model is similar to the NB model, we consider the former as an alternate model for overdispersed count data. The score test has an advantage over the LRT and the Wald test in that the score test only requires that the parameter of interest be estimated under the null hypothesis. This paper proposes a score test for overdispersion based on the GP model and compares the power of the test with the LRT and Wald tests. A simulation study indicates the score test based on asymptotic standard Normal distribution is more appropriate in practical application for higher empirical power, however, it underestimates the nominal significance level, especially in small sample situations, and examples illustrate the results of comparing the candidate tests between the Poisson and GP models. A bootstrap test is also proposed to adjust the underestimation of nominal level in the score statistic when the sample size is small. The simulation study indicates the bootstrap test has significance level closer to nominal size and has uniformly greater power than the score test based on asymptotic standard Normal distribution. From a practical perspective, we suggest that, if the score test gives even a weak indication that the Poisson model is inappropriate, say at the 0.10 significance level, we advise the more accurate bootstrap procedure as a better test for comparing whether the GP model is more appropriate than Poisson model. Finally, the Vuong test is illustrated to choose between GP and NB2 models for the same dataset.     

On the generalized poisson regression mixture model for mapping quantitative trait loci with count data

Statistical methods for mapping quantitative trait loci (QTL) have been extensively studied. While most existing methods assume normal distribution of the phenotype, the normality assumption could be easily violated when phenotypes are measured in counts. One natural choice to deal with count traits is to apply the classical Poisson regression model. However, conditional on covariates, the Poisson assumption of mean-variance equality may not be valid when data are potentially under- or overdispersed. In this article, we propose an interval-mapping approach for phenotypes measured in counts. We model the effects of QTL through a generalized Poisson regression model and develop efficient likelihood-based inference procedures. This approach, implemented with the EM algorithm, allows for a genomewide scan for the existence of QTL throughout the entire genome. The performance of the proposed method is evaluated through extensive simulation studies along with comparisons with existing approaches such as the Poisson regression and the generalized estimating equation approach. An application to a rice tiller number data set is given. Our approach provides a standard procedure for mapping QTL involved in the genetic control of complex traits measured in counts.     

Effect of nonindependent substitution on phylogenetic accuracy

All current phylogenetic methods assume that DNA substitutions are independent among sites. However, ample empirical evidence suggests that the process of substitution is not independent but is, in fact, temporally and spatially correlated. The robustness of several commonly used phylogenetic methods to the assumption of independent substitution is examined. A compound Poisson process is used to model DNA substitution. This model assumes that substitution events are Poisson-distributed in time and that the number of substitutions associated with each event is geometrically distributed. The asymptotic properties of phylogenetic methods do not appear to change under a compound Poisson process of DNA substitution. Moreover, the rank order of the performance of different methods does not change. However, all phylogenetic methods become less efficient when substitution follows a compound Poisson process.     

Spatial modeling of data with excessive zeros applied to reindeer pellet‐group counts

We analyze a real data set pertaining to reindeer fecal pellet‐group counts obtained from a survey conducted in a forest area in northern Sweden. In the data set, over 70% of counts are zeros, and there is high spatial correlation. We use conditionally autoregressive random effects for modeling of spatial correlation in a Poisson generalized linear mixed model (GLMM), quasi‐Poisson hierarchical generalized linear model (HGLM), zero‐inflated Poisson (ZIP), and hurdle models. The quasi‐Poisson HGLM allows for both under‐ and overdispersion with excessive zeros, while the ZIP and hurdle models allow only for overdispersion. In analyzing the real data set, we see that the quasi‐Poisson HGLMs can perform better than the other commonly used models, for example, ordinary Poisson HGLMs, spatial ZIP, and spatial hurdle models, and that the underdispersed Poisson HGLMs with spatial correlation fit the reindeer data best. We develop R codes for fitting these models using a unified algorithm for the HGLMs. Spatial count response with an extremely high proportion of zeros, and underdispersion can be successfully modeled using the quasi‐Poisson HGLM with spatial random effects.     

Point and Interval Estimation of the Population Size Using a Zero‐Truncated Negative Binomial Regression Model

This paper presents the zero‐truncated negative binomial regression model to estimate the population size in the presence of a single registration file. The model is an alternative to the zero‐truncated Poisson regression model and it may be useful if the data are overdispersed due to unobserved heterogeneity. Horvitz–Thompson point and interval estimates for the population size are derived, and the performance of these estimators is evaluated in a simulation study. To illustrate the model, the size of the population of opiate users in the city of Rotterdam is estimated. In comparison to the Poisson model, the zero‐truncated negative binomial regression model fits these data better and yields a substantially higher population size estimate. (© 2008 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)     

Some extensions of a linear model for categorical variables

The Grizzle-Starmer-Koch (GSK) model is extended to include the traditional log-linear model and a general class of Poisson and conditional Poisson distributions. Estimators of the model parameters are defined under general exact and stochastic linear constraints.     

Simulation of deformable models with the Poisson equation

In this paper, we present a new methodology for the deformation of soft objects by drawing an analogy between the Poisson equation and elastic deformation from the viewpoint of energy propagation. The potential energy stored due to a deformation caused by an external force is calculated and treated as the source injected into the Poisson system, as described by the law of conservation of energy. An improved Poisson model is developed for propagating the energy generated by the external force in a natural manner. An autonomous cellular neural network (CNN) model is established by using the analogy between the Poisson equation and CNN to solve the Poisson model for the real-time requirement of soft object deformation. A method is presented to derive the internal forces from the potential energy distribution. The proposed methodology models non-linear materials with the non-linear Poisson equation and thus non-linear CNN, rather than geometric non-linearity. It not only deals with large-range deformations, but also accommodates isotropic, anisotropic and inhomogeneous materials by simply modifying constitutive coefficients. A haptic virtual reality system has been developed for deformation simulation with force feedback. Examples are presented to demonstrate the efficiency of the proposed methodology.     

Comparison of Bayesian methods for flexible modeling of spatial risk surfaces in disease mapping

Bayesian hierarchical models usually model the risk surface on the same arbitrary geographical units for all data sources. Poisson/gamma random field models overcome this restriction as the underlying risk surface can be specified independently to the resolution of the data. Moreover, covariates may be considered as either excess or relative risk factors. We compare the performance of the Poisson/gamma random field model to the Markov random field (MRF)‐based ecologic regression model and the Bayesian Detection of Clusters and Discontinuities (BDCD) model, in both a simulation study and a real data example. We find the BDCD model to have advantages in situations dominated by abruptly changing risk while the Poisson/gamma random field model convinces by its flexibility in the estimation of random field structures and by its flexibility incorporating covariates. The MRF‐based ecologic regression model is inferior. WinBUGS code for Poisson/gamma random field models is provided.     

Bringing consistency to simulation of population models--Poisson simulation as a bridge between micro and macro simulation

Population models concern collections of discrete entities such as atoms, cells, humans, animals, etc., where the focus is on the number of entities in a population. Because of the complexity of such models, simulation is usually needed to reproduce their complete dynamic and stochastic behaviour. Two main types of simulation models are used for different purposes, namely micro-simulation models, where each individual is described with its particular attributes and behaviour, and macro-simulation models based on stochastic differential equations, where the population is described in aggregated terms by the number of individuals in different states. Consistency between micro- and macro-models is a crucial but often neglected aspect. This paper demonstrates how the Poisson Simulation technique can be used to produce a population macro-model consistent with the corresponding micro-model. This is accomplished by defining Poisson Simulation in strictly mathematical terms as a series of Poisson processes that generate sequences of Poisson distributions with dynamically varying parameters. The method can be applied to any population model. It provides the unique stochastic and dynamic macro-model consistent with a correct micro-model. The paper also presents a general macro form for stochastic and dynamic population models. In an appendix Poisson Simulation is compared with Markov Simulation showing a number of advantages. Especially aggregation into state variables and aggregation of many events per time-step makes Poisson Simulation orders of magnitude faster than Markov Simulation. Furthermore, you can build and execute much larger and more complicated models with Poisson Simulation than is possible with the Markov approach.     

Simulation of deformable models with the Poisson equation

In this paper, we present a new methodology for the deformation of soft objects by drawing an analogy between the Poisson equation and elastic deformation from the viewpoint of energy propagation. The potential energy stored due to a deformation caused by an external force is calculated and treated as the source injected into the Poisson system, as described by the law of conservation of energy. An improved Poisson model is developed for propagating the energy generated by the external force in a natural manner. An autonomous cellular neural network (CNN) model is established by using the analogy between the Poisson equation and CNN to solve the Poisson model for the real-time requirement of soft object deformation. A method is presented to derive the internal forces from the potential energy distribution. The proposed methodology models non-linear materials with the non-linear Poisson equation and thus non-linear CNN, rather than geometric non-linearity. It not only deals with large-range deformations, but also accommodates isotropic, anisotropic and inhomogeneous materials by simply modifying constitutive coefficients. A haptic virtual reality system has been developed for deformation simulation with force feedback. Examples are presented to demonstrate the efficiency of the proposed methodology.     

Minimum Hellinger distance estimation for k-component poisson mixture with random effects

Summary .   The k-component Poisson regression mixture with random effects is an effective model in describing the heterogeneity for clustered count data arising from several latent subpopulations. However, the residual maximum likelihood estimation (REML) of regression coefficients and variance component parameters tend to be unstable and may result in misleading inferences in the presence of outliers or extreme contamination. In the literature, the minimum Hellinger distance (MHD) estimation has been investigated to obtain robust estimation for finite Poisson mixtures. This article aims to develop a robust MHD estimation approach for k-component Poisson mixtures with normally distributed random effects. By applying the Gaussian quadrature technique to approximate the integrals involved in the marginal distribution, the marginal probability function of the k-component Poisson mixture with random effects can be approximated by the summation of a set of finite Poisson mixtures. Simulation study shows that the MHD estimates perform satisfactorily for data without outlying observation(s), and outperform the REML estimates when data are contaminated. Application to a data set of recurrent urinary tract infections (UTI) with random institution effects demonstrates the practical use of the robust MHD estimation method.     

Background stratified Poisson regression analysis of cohort data

Background stratified Poisson regression is an approach that has been used in the analysis of data derived from a variety of epidemiologically important studies of radiation-exposed populations, including uranium miners, nuclear industry workers, and atomic bomb survivors. We describe a novel approach to fit Poisson regression models that adjust for a set of covariates through background stratification while directly estimating the radiation-disease association of primary interest. The approach makes use of an expression for the Poisson likelihood that treats the coefficients for stratum-specific indicator variables as ‘nuisance’ variables and avoids the need to explicitly estimate the coefficients for these stratum-specific parameters. Log-linear models, as well as other general relative rate models, are accommodated. This approach is illustrated using data from the Life Span Study of Japanese atomic bomb survivors and data from a study of underground uranium miners. The point estimate and confidence interval obtained from this ‘conditional’ regression approach are identical to the values obtained using unconditional Poisson regression with model terms for each background stratum. Moreover, it is shown that the proposed approach allows estimation of background stratified Poisson regression models of non-standard form, such as models that parameterize latency effects, as well as regression models in which the number of strata is large, thereby overcoming the limitations of previously available statistical software for fitting background stratified Poisson regression models.     

Statistical methods for estimating doubling time in in vitro cell growth

Summary Doubling time has been widely used to represent the growth pattern of cells. A traditional method for finding the doubling time is to apply gray-scaled cells, where the logarithmic transformed scale is used. As an alternative statistical method, the log-linear model was recently proposed, for which actual cell numbers are used instead of the transformed gray-scaled cells. In this paper, I extend the log-linear model and propose the extended log-linear model. This model is designed for extra-Poisson variation, where the log-linear model produces the less appropriate estimate of the doubling time. Moreover, I compare statistical properties of the gray-scaled method, the log-linear model, and the extended log-linear model. For this purpose, I perform a Monte Carlo simulation study with three data-generating models: the additive error model, the multiplicative error model, and the overdispersed Poisson model. From the simulation study, I found that the gray-scaled method highly depends on the normality assumption of the gray-scaled cells; hence, this method is appropriate when the error model is multiplicative with the log-normally distributed errors. However, it is less efficient for other types of error distributions, especially when the error model is additive or the errors follow the Poisson distribution. The estimated standard error for the doubling time is not accurate in this case. The log-linear model was found to be efficient when the errors follow the Poisson distribution or nearly Poisson distribution. The efficiency of the log-linear model was decreased accordingly as the overdispersion increased, compared to the extended log-linear model. When the error model is additive or multiplicative with Gamma-distributed errors, the log-linear model is more efficient than the gray-scaled method. The extended log-linear model performs well overall for all three data-generating models. The loss of efficiency of the extended log-linear model is observed only when the error model is multiplicative with log-normally distributed errors, where the gray-scaled method is appropriate. However, the extended log-linear model is more efficient than the log-linear model in this case.     

Promotion time models with time-changing exposure and heterogeneity: application to infectious diseases

Promotion time models have been recently adapted to the context of infectious diseases to take into account discrete and multiple exposures. However, Poisson distribution of the number of pathogens transmitted at each exposure was a very strong assumption and did not allow for inter-individual heterogeneity. Bernoulli, the negative binomial, and the compound Poisson distributions were proposed as alternatives to Poisson distribution for the promotion time model with time-changing exposure. All were derived within the frailty model framework. All these distributions have a point mass at zero to take into account non-infected people. Bernoulli distribution, the two-component cure rate model, was extended to multiple exposures. Contrary to the negative binomial and the compound Poisson distributions, Bernoulli distribution did not enable to connect the number of pathogens transmitted to the delay between transmission and infection detection. Moreover, the two former distributions enable to account for inter-individual heterogeneity. The delay to surgical site infection was an example of single exposure. The probability of infection was very low; thus, estimation of the effect of selected risk factors on that probability obtained with Bernoulli and Poisson distributions were very close. The delay to nosocomial urinary tract infection was a multiple exposure example. The probabilities of pathogen transmission during catheter placement and catheter presence were estimated. Inter-individual heterogeneity was very high, and the fit was better with the compound Poisson and the negative binomial distributions. The proposed models proved to be also mechanistic. The negative binomial and the compound Poisson distributions were useful alternatives to account for inter-individual heterogeneity.