Still-births among the offspring of male radiation workers at the Sellafield nuclear reprocessing plant: detailed results and statistical aspects

Summary. This study investigates whether there was evidence of increasing risk of still-birth with increasing paternal exposure to ionizing radiation received during employment at the Sellafield nuclear installation before the child was conceived. A significant positive association is found between the total paternal preconceptional exposure to external ionizing radiation and the risk of still-birth (after adjustment for year of birth, social class, birth order and paternal age, odds ratio at 100 mSv 1.24 (95% confidence interval 1.04–1.45)). A summary of the principal scientific findings of this study has been published in the Lancet . This paper describes in detail the statistical methods that were used in the investigation and presents the results in full.     

Estimation of Hazard, Density and Survivor Functions for Randomly Censored Data

Maximum likelihood estimation and goodness-of-fit techniques are used within a competing risks framework to obtain maximum likelihood estimates of hazard, density, and survivor functions for randomly right-censored variables. Goodness-of- fit techniques are used to fit distributions to the crude lifetimes, which are used to obtain an estimate of the hazard function, which, in turn, is used to construct the survivor and density functions of the net lifetime of the variable of interest. If only one of the crude lifetimes can be adequately characterized by a parametric model, then semi-parametric estimates may be obtained using a maximum likelihood estimate of one crude lifetime and the empirical distribution function of the other. Simulation studies show that the survivor function estimates from crude lifetimes compare favourably with those given by the product-limit estimator when crude lifetimes are chosen correctly. Other advantages are discussed.     

Nonparametric smoothing in the analysis of air pollution and respiratory illness

While most of epidemiology is observational, rather than experimental, the culture of epidemiology is still derived from agricultural experiments, rather than other observational fields, such as astronomy or economics. The mismatch is made greater as focus has turned to continue risk factors, multifactorial outcomes, and outcomes with large variation unexplainable by available risk factors. The analysis of such data is often viewed as hypothesis testing with statistical control replacing randomization. However, such approaches often test restricted forms of the hypothesis being investigated, such as the hypothesis of a linear association, when there is no prior empirical or theoretical reason to believe that if an association exists, it is linear. In combination with the large nonstochastic sources of error in such observational studies, this suggests the more flexible alternative of exploring the association. Conclusions on the possible causal nature of any discovered association will rest on the coherence and consistency of multiple studies. Nonparametric smoothing in general, and generalized additive models in particular, represent an attractive approach to such problems. This is illustrated using data examining the relationship between particulate air pollution and daily mortality in Birmingham, Alabama; between particulate air pollution, ozone, and SO₂ and daily hospital admissions for respiratory illness in Philadelphia; and between ozone and particulate air pollution and coughing episodes in children in six eastern U.S. cities. The results indicate that airborne particles and ozone are associated with adverse health outcomes at very low concentrations, and that there are likely no thresholds for these relationships.     

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.     

我国推行住宅抵押贷款证券化问题分析

目前,在我国推行住宅抵押贷款证券化存在着抵押贷款规模过小、房地产开发融资渠道不宽、商业银行积极性不高、信用制度不健全、法律环境不完善等问题。我国还不具备大规模推广住宅抵押贷款证券化的条件。     

Conditional Likelihood Estimators for Hidden Markov Models and Stochastic Volatility Models

ABSTRACT.  This paper develops a new contrast process for parametric inference of general hidden Markov models, when the hidden chain has a non-compact state space. This contrast is based on the conditional likelihood approach, often used for ARCH-type models. We prove the strong consistency of the conditional likelihood estimators under appropriate conditions. The method is applied to the Kalman filter (for which this contrast and the exact likelihood lead to asymptotically equivalent estimators) and to the discretely observed stochastic volatility models.     

A Bayesian Hierarchical Model for the Evaluation of a Website

Consider a website and the surfers visiting its pages. A typical issue of interest, for example while monitoring an advertising campaign, concerns whether a specific page has been designed successfully, i.e. is able to attract surfers or address them to other pages within the site. We assume that the surfing behaviour is fully described by the transition probabilities from one page to another, so that a clickstream (sequence of consecutively visited pages) can be viewed as a finite-state-space Markov chain. We then implement a variety of hierarchical prior distributions on the multivariate logits of the transition probabilities and define, for each page, a content effect and a link effect. The former measures the attractiveness of the page due to its contents, while the latter signals its ability to suggest further interesting links within the site. Moreover, we define an additional effect, representing overall page success, which incorporates both effects previously described. Using WinBUGS, we provide estimates and credible intervals for each of the above effects and rank pages accordingly.     

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.