Geometric Method and Generalized Linear Models. Two Opposite Multiparametric Approaches Illustrated on a Sample of Pituitary Adenomas

We used two statistical methods to identify prognostic factors: a log-linear model (logistic and COX regression, based on the notions of linearity and multiplicative relative risk), and the CORICO method (ICOnography of CORrelations) based on the geometric significance of the correlation coefficient. We applied the methods to two different situations (a "case-control study' and a "historical cohort'). We show that the geometric exploratory tool is particularly suited to the analysis of small samples with a large number of variables. It could save time when setting up new study protocols. In this instance, the geometric approach highlighted, without preconceived ideas, the potential role of multihormonality in the course of pituitary adenoma and the unexpected influence of the date of tumour excision on the risk attached to haemorrhage.     

Estimation of Metabolic Rate Constants in PBPK‐Models from Liver Slice Experiments: What Are the Experimental Needs?

A mechanistic model is presented describing the clearance of a compound in a precision-cut liver slice that is incubated in a culture medium. The problem of estimating metabolic rate constants in PBPK models from liver slice experiments is discussed using identifiability analysis. From the identifiability problem analysis, it appears that in addition to the clearance, the compound's free fraction in the slice and the diffusion rate of the exchange of the compound between culture medium and liver slice should be identified. In addition, knowledge of the culture medium volume, the slice volume, the compound's free fraction, and octanol-water-based partition between medium and slice is presupposed. The formal solution for identification is discussed from the perspective of experimental practice. A formally necessary condition for identification is the sampling of parent compound in liver slice or culture medium. However, due to experimental limitations and errors, sampling the parent compound in the slice together with additional sampling of metabolite pooled from the medium and the slice is required for identification in practice. Moreover, it appears that identification results are unreliable when the value of the intrinsic clearance exceeds the value of the diffusion coefficient, a condition to be verified a posteriori.     

Uncertainty Analysis for Computer Model Projections of Hurricane Losses

Projecting losses associated with hurricanes is a complex and difficult undertaking that is wrought with uncertainties. Hurricane Charley, which struck southwest Florida on August 13, 2004, illustrates the uncertainty of forecasting damages from these storms. Due to shifts in the track and the rapid intensification of the storm, real-time estimates grew from 2 to 3 billion dollars in losses late on August 12 to a peak of 50 billion dollars for a brief time as the storm appeared to be headed for the Tampa Bay area. The storm hit the resort areas of Charlotte Harbor near Punta Gorda and then went on to Orlando in the central part of the state, with early poststorm estimates converging on a damage estimate in the 28 to 31 billion dollars range. Comparable damage to central Florida had not been seen since Hurricane Donna in 1960. The Florida Commission on Hurricane Loss Projection Methodology (FCHLPM) has recognized the role of computer models in projecting losses from hurricanes. The FCHLPM established a professional team to perform onsite (confidential) audits of computer models developed by several different companies in the United States that seek to have their models approved for use in insurance rate filings in Florida. The team's members represent the fields of actuarial science, computer science, meteorology, statistics, and wind and structural engineering. An important part of the auditing process requires uncertainty and sensitivity analyses to be performed with the applicant's proprietary model. To influence future such analyses, an uncertainty and sensitivity analysis has been completed for loss projections arising from use of a Holland B parameter hurricane wind field model. Uncertainty analysis quantifies the expected percentage reduction in the uncertainty of wind speed and loss that is attributable to each of the input variables.     

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.     

Optimal sampling for repeated binary measurements

The authors consider the optimal design of sampling schedules for binary sequence data. They propose an approach which allows a variety of goals to be reflected in the utility function by including deterministic sampling cost, a term related to prediction, and if relevant, a term related to learning about a treatment effect To this end, they use a nonparametric probability model relying on a minimal number of assumptions. They show how their assumption of partial exchangeability for the binary sequence of data allows the sampling distribution to be written as a mixture of homogeneous Markov chains of order k. The implementation follows the approach of Quintana & Müller (2004), which uses a Dirichlet process prior for the mixture.     

经济法教学实践性模式探讨

现行高校经济法教学模式一般只注重向学生传授基本的经济法学原理和相关法律知识,却忽视对学生实践能力、操作能力和思考能力的培养,造成教学和现实的脱节,同时也面临着学科自身发展瓶颈与学生就业前景暗淡的尴尬.针对经济法课程新、专、广的特点,本着培养学生经济法法律意识和法律实践能力的目的,从教学环节入手,以实践性理念为指导来设定教学目标、安排教学内容、运用多样化的教学方法和手段,构建经济法教学的实践性模式,不失为一条出路.     

古老而鲜活的地域文化记忆——论绍兴的非物质文化遗产

非物质文化遗产是地城文化的重要组成部分.从形态学视阈来审视文化名城绍兴的非物质文化资源,以当代的意识发现和承传这份地域文化遗产,对于挖掘越文化古老的生命记忆、保存活态的文化基因,使地域文化呈现出鲜明的载体均有独特的意义.     

经济发展、资源功能与中国的配置绩效

经济发展理论高度重视各种资源等劳动对象的开发利用。西方经济学的信仰者由于自身存在的认识论缺陷，难以科学认识劳动对象与经济发展的内在关系，进而也难以科学论述资源在发展理论及其模型中的作用和地位。因此，必须遵循马克思的方法论，从理论为实际的反映入手，建立科学的分析模型，以此指导中国经济发展方式的转变，建立生态与经济相协调的可持续发展的资源及能源支撑体系，调整、优化资源及能源的供给与需求结构。     

利用WALL构建双主教学模式深化大学英语教学改革

作为大学英语改革的主要内容，WALL（网络辅助语言学习）为大学英语改革带来了勃勃生机。本文分析了借助WALL构建大学英语双主模式，即教师主导，学生为认知主体的教学模式的实践意义。并根据相关理论分析了新型模式下教师和学生各自的作用和角色，对如何构建双主模式深化大学英语教学改革提出了一些设想。     

A modification of Honoré's triple-link model in the synoptic problem

Summary.  In New Testament studies, the synoptic problem is concerned with the relationships between the gospels of Matthew, Mark and Luke. In an earlier paper a careful specification in probabilistic terms was set up of Honoré's triple-link model. In the present paper, a modification of Honoré's model is proposed. As previously, counts of the numbers of verbal agreements between the gospels are examined to investigate which of the possible triple-link models appears to give the best fit to the data, but now using the modified version of the model and additional sets of data.