Human Salmonellosis: Estimation of Dose-Illness from Outbreak Data

The quantification of the relationship between the amount of microbial organisms ingested and a specific outcome such as infection, illness, or mortality is a key aspect of quantitative risk assessment. A main problem in determining such dose-response models is the availability of appropriate data. Human feeding trials have been criticized because only young healthy volunteers are selected to participate and low doses, as often occurring in real life, are typically not considered. Epidemiological outbreak data are considered to be more valuable, but are more subject to data uncertainty. In this article, we model the dose-illness relationship based on data of 20 Salmonella outbreaks, as discussed by the World Health Organization. In particular, we model the dose-illness relationship using generalized linear mixed models and fractional polynomials of dose. The fractional polynomial models are modified to satisfy the properties of different types of dose-illness models as proposed by Teunis et al . Within these models, differences in host susceptibility (susceptible versus normal population) are modeled as fixed effects whereas differences in serovar type and food matrix are modeled as random effects. In addition, two bootstrap procedures are presented. A first procedure accounts for stochastic variability whereas a second procedure accounts for both stochastic variability and data uncertainty. The analyses indicate that the susceptible population has a higher probability of illness at low dose levels when the combination pathogen-food matrix is extremely virulent and at high dose levels when the combination is less virulent. Furthermore, the analyses suggest that immunity exists in the normal population but not in the susceptible population.     

线性科学与非线性科学哲学思想研究

在简述线性科学的科学基础、科学方法和哲学思想的基础上，研究了非线性科学的科学基础、科学方法和哲学思想，其中较为详细地探讨了非线性科学的哲学范畴和哲学思想，认为要多角度观察事物，要从变化中认识主要矛盾，事物的发展是多元竞争与协同的统一，这一结果将对非线性科学的哲学思想的进一步研究有一定的启发和借鉴作用。     

独立学院应用性人才培养模式的构建与探索

独立学院是我国现行高教体制的突破与革新，既不同于传统的公办普通高校，又有别于已有的民办高校和职业技术学院。随着高等教育大众化，面对着竞争愈演愈烈的人才市场，独立学院如何在高等教育竞争中的勇立潮头，赢得一席之地，必须就“独立学院应用性人才培养模式的构建”进行认真的研究与探索，根据社会对人才需求呈现出多样化趋势的实际，找准学院定位，明确办学理念，理清办学思路，创新培养模式，全力打造“应用性”人才。     

ADDITIVE MODELS WITH PREDICTORS SUBJECT TO MEASUREMENT ERROR

This paper develops a likelihood‐based method for fitting additive models in the presence of measurement error. It formulates the additive model using the linear mixed model representation of penalized splines. In the presence of a structural measurement error model, the resulting likelihood involves intractable integrals, and a Monte Carlo expectation maximization strategy is developed for obtaining estimates. The method's performance is illustrated with a simulation study.     

An empirical likelihood goodness-of-fit test for time series

Summary. Standard goodness-of-fit tests for a parametric regression model against a series of nonparametric alternatives are based on residuals arising from a fitted model. When a parametric regression model is compared with a nonparametric model, goodness-of-fit testing can be naturally approached by evaluating the likelihood of the parametric model within a nonparametric framework. We employ the empirical likelihood for an α -mixing process to formulate a test statistic that measures the goodness of fit of a parametric regression model. The technique is based on a comparison with kernel smoothing estimators. The empirical likelihood formulation of the test has two attractive features. One is its automatic consideration of the variation that is associated with the nonparametric fit due to empirical likelihood's ability to Studentize internally. The other is that the asymptotic distribution of the test statistic is free of unknown parameters, avoiding plug-in estimation. We apply the test to a discretized diffusion model which has recently been considered in financial market analysis.     

图的点星荫度

引入了图的点星荫度的概念,研究了一般图的点星荫度的上界,着重讨论了平面图和外平面图的点星荫度。     

Pseudo–Modelling of Outliers for Estimation of Regression And Time Series Models

This paper documents situations where the variance inflation model for outliers has undesirable properties. The model is commonly used to accommodate outliers in a Bayesian analysis of regression and time series models. The alternative approach provided here does not suffer from these undesirable properties but gives inferences similar to those of the variance inflation model when this is appropriate. It can be used with regression, time series, and regression with correlated errors in a unified way, and adheres to the scientific principle that inference should be based on the data after obvious outliers have been discarded. Only one parameter is required for outliers; it is interpretable as the a priori willingness to remove observations from the analysis.     

Defining the linear portion of a sigmoid‐shaped curve: bend points

Formulae are provided that define the ‘bend points’, the beginning and end of the essentially linear dose–response region, for the four‐parameter logistic model. The formulae are expressed in both response and dose units. The derivation of the formulae is shown in order to illustrate the general nature of the methodology. Examples are given that describe how the formulae may be used while planning and conducting bioassays. Copyright © 2003 John Wiley & Sons, Ltd.     

Exposure Reconstruction for the TCDD-Exposed NIOSH Cohort Using a Concentration- and Age-Dependent Model of Elimination

Recent studies demonstrating a concentration dependence of elimination of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) suggest that previous estimates of exposure for occupationally exposed cohorts may have underestimated actual exposure, resulting in a potential overestimate of the carcinogenic potency of TCDD in humans based on the mortality data for these cohorts. Using a database on U.S. chemical manufacturing workers potentially exposed to TCDD compiled by the National Institute for Occupational Safety and Health (NIOSH), we evaluated the impact of using a concentration- and age-dependent elimination model (CADM) (Aylward et al., 2005) on estimates of serum lipid area under the curve (AUC) for the NIOSH cohort. These data were used previously by Steenland et al. (2001) in combination with a first-order elimination model with an 8.7-year half-life to estimate cumulative serum lipid concentration (equivalent to AUC) for these workers for use in cancer dose-response assessment. Serum lipid TCDD measurements taken in 1988 for a subset of the cohort were combined with the NIOSH job exposure matrix and work histories to estimate dose rates per unit of exposure score. We evaluated the effect of choices in regression model (regression on untransformed vs. ln-transformed data and inclusion of a nonzero regression intercept) as well as the impact of choices of elimination models and parameters on estimated AUCs for the cohort. Central estimates for dose rate parameters derived from the serum-sampled subcohort were applied with the elimination models to time-specific exposure scores for the entire cohort to generate AUC estimates for all cohort members. Use of the CADM resulted in improved model fits to the serum sampling data compared to the first-order models. Dose rates varied by a factor of 50 among different combinations of elimination model, parameter sets, and regression models. Use of a CADM results in increases of up to five-fold in AUC estimates for the more highly exposed members of the cohort compared to estimates obtained using the first-order model with 8.7-year half-life. This degree of variation in the AUC estimates for this cohort would affect substantially the cancer potency estimates derived from the mortality data from this cohort. Such variability and uncertainty in the reconstructed serum lipid AUC estimates for this cohort, depending on elimination model, parameter set, and regression model, have not been described previously and are critical components in evaluating the dose-response data from the occupationally exposed populations.     

一类两个相同部件并联的可修系统的稳定性

研究一类两个相同部件并联的可修系统．使用泛函分析方法，特别是Banach空间上的线性算子理论，证明了严格占优本征值的存在性，以及系统解的渐近稳定性，线性稳定性和指数稳定性．