Using In Vitro High‐Throughput Screening Data for Predicting Benzo[k]Fluoranthene Human Health Hazards

Today there are more than 80,000 chemicals in commerce and the environment. The potential human health risks are unknown for the vast majority of these chemicals as they lack human health risk assessments, toxicity reference values, and risk screening values. We aim to use computational toxicology and quantitative high‐throughput screening (qHTS) technologies to fill these data gaps, and begin to prioritize these chemicals for additional assessment. In this pilot, we demonstrate how we were able to identify that benzo[k]fluoranthene may induce DNA damage and steatosis using qHTS data and two separate adverse outcome pathways (AOPs). We also demonstrate how bootstrap natural spline‐based meta‐regression can be used to integrate data across multiple assay replicates to generate a concentration–response curve. We used this analysis to calculate an in vitro point of departure of 0.751 μM and risk‐specific in vitro concentrations of 0.29 μM and 0.28 μM for 1:1,000 and 1:10,000 risk, respectively, for DNA damage. Based on the available evidence, and considering that only a single HSD17B4 assay is available, we have low overall confidence in the steatosis hazard identification. This case study suggests that coupling qHTS assays with AOPs and ontologies will facilitate hazard identification. Combining this with quantitative evidence integration methods, such as bootstrap meta‐regression, may allow risk assessors to identify points of departure and risk‐specific internal/in vitro concentrations. These results are sufficient to prioritize the chemicals; however, in the longer term we will need to estimate external doses for risk screening purposes, such as through margin of exposure methods.     

Choosing Prior Hyperparameters: With Applications to Time-Varying Parameter Models

Time-varying parameter models with stochastic volatility are widely used to study macroeconomic and financial data. These models are almost exclusively estimated using Bayesian methods. A common practice is to focus on prior distributions that themselves depend on relatively few hyperparameters such as the scaling factor for the prior covariance matrix of the residuals governing time variation in the parameters. The choice of these hyperparameters is crucial because their influence is sizeable for standard sample sizes. In this article, we treat the hyperparameters as part of a hierarchical model and propose a fast, tractable, easy-to-implement, and fully Bayesian approach to estimate those hyperparameters jointly with all other parameters in the model. We show via Monte Carlo simulations that, in this class of models, our approach can drastically improve on using fixed hyperparameters previously proposed in the literature. Supplementary materials for this article are available online.     

Outlier detection in high-dimensional regression model

An outlier is defined as an observation that is significantly different from the others in its dataset. In high-dimensional regression analysis, datasets often contain a portion of outliers. It is important to identify and eliminate the outliers for fitting a model to a dataset. In this paper, a novel outlier detection method is proposed for high-dimensional regression problems. The leave-one-out idea is utilized to construct a novel outlier detection measure based on distance correlation, and then an outlier detection procedure is proposed. The proposed method enjoys several advantages. First, the outlier detection measure can be simply calculated, and the detection procedure works efficiently even for high-dimensional regression data. Moreover, it can deal with a general regression, which does not require specification of a linear regression model. Finally, simulation studies show that the proposed method behaves well for detecting outliers in high-dimensional regression model and performs better than some other competing methods.     

Bayesian Design of Special Type of Double Sampling Plans for Compliance Testing

Bayesian acceptance sampling plans, which utilize prior information on the process variation, can be employed as an alternative to conventional types of plans for taking decisions on the disposition of submitted lots. A special type of double sampling inspection plans by attributes with small acceptance numbers using Bayesian methodology is presented in this paper emphasizing its significance over small acceptance number single sampling plans. The procedures for designing such sampling plans for specified degree of discrimination which would ensure protection to the producer and consumer are discussed with illustrations under the conditions for the application of gamma-Poisson distribution.     

Elasticity function of a discrete random variable and its properties

Elasticity (or elasticity function) is a new concept that allows us to characterize the probability distribution of any random variable in the same way as characteristic functions and hazard and reverse hazard functions do. Initially defined for continuous variables, it was necessary to extend the definition of elasticity and study its properties in the case of discrete variables. A first attempt to define discrete elasticity is seen in Veres-Ferrer and Pavía (2014a). This paper develops this definition and makes a comparative study of its properties, relating them to the properties shown by discrete hazard and reverse hazard, as both defined in Chechile (2011). Similar to continuous elasticity, one of the most interesting properties of discrete elasticity focuses on the rate of change that this undergoes throughout its support. This paper centers on the study of the rate of change and develops a set of properties that allows us to carry out a detailed analysis. Finally, it addresses the calculation of the elasticity for the resulting variable obtained from discretizing a continuous random variable, distinguishing whether its domain is in real positives or negatives.     

浅析本科院校《导游实务》实践教学的改革与创新

本科院校《导游实务》实践教学的改革与创新,是一个急需解决的课题。针对目前本科院校《导游实务》实践教学效果不佳、教师实践经验不足以及学校对学生职业素养培养不够等问题,提出学校应该从教学手段和方法、师资队伍结构以及教学理念上进行改革,丰富实践教学形式、科学调配师资结构、改革招生方式、重视学生导游素质的培养。     

Stochastic properties of the mixed accelerated hazard models

The accelerated hazard model in survival analysis assumes that the covariate effect acts the time scale of the baseline hazard rate. In this paper, we study the stochastic properties of the mixed accelerated hazard model since the covariate is considered basically unobservable. We build dependence structure between the population variable and the covariate, and also present some preservation properties. Using some well-known stochastic orders, we compare two mixed accelerated hazards models arising out of different choices of distributions for unobservable covariates or different baseline hazard rate functions.     

Diagnostics for quasi-likelihood nonlinear models

Quasi-likelihood nonlinear models (QLNMs) are an extension of generalized linear model and include a widen class of models as special cases. This article investigates some diagnostic methods in QLNMs. An equivalency between a case-deletion model and a mean-shift outlier model in QLNM is established. Two simulation study and a real dataset are used to illustrate the proposed diagnostic methods.