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.     

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.     

On the preservation of copula structure under truncation

The author characterizes the copula associated with the bivariate survival model of Clayton (1978) as the only absolutely continuous copula that is preserved under bivariate truncation.     

Semiparametric linear transformation models for current status data

Current status data arise when the death of every subject in a study cannot be determined precisely, but is known only to have occurred before or after a random monitoring time. The authors discuss the analysis of such data under semiparametric linear transformation models for which they propose a general inference procedure based on estimating functions. They determine the properties of the estimates they propose for the regression parameters of the model and illustrate their technique using tumorigenicity data.     

Estimation of the parameters of symmetric stable ARMA and ARMA–GARCH models

In this article, we first propose the modified Hannan–Rissanen Method for estimating the parameters of autoregressive moving average (ARMA) process with symmetric stable noise and symmetric stable generalized autoregressive conditional heteroskedastic (GARCH) noise. Next, we propose the modified empirical characteristic function method for the estimation of GARCH parameters with symmetric stable noise. Further, we show the efficiency, accuracy and simplicity of our methods with Monte-Carlo simulation. Finally, we apply our proposed methods to model the financial data.     

ASSESSING THE RELATIONSHIP BETWEEN SYMPTOMS OF ALLERGIC RHINOCONJUNCTIVITIS AND POLLEN COUNTS

The relationship between daily pollen counts during the peak pollen season and hay fever symptoms in known sufferers of pollen allergy was investigated in a Sydney hospital‐based study. This paper develops statistical models for both the short term (day to day) associations and the longer term relationships between these time series. Possible effects of asthma status are investigated. The analyses illustrate how different relationships between time series may be explored in a simple way by working on different time scales with suitably transformed variables.     

Multiparameter evidence synthesis in epidemiology and medical decision-making: current approaches

Summary.  Alongside the development of meta-analysis as a tool for summarizing research literature, there is renewed interest in broader forms of quantitative synthesis that are aimed at combining evidence from different study designs or evidence on multiple parameters. These have been proposed under various headings: the confidence profile method, cross-design synthesis, hierarchical models and generalized evidence synthesis. Models that are used in health technology assessment are also referred to as representing a synthesis of evidence in a mathematical structure. Here we review alternative approaches to statistical evidence synthesis, and their implications for epidemiology and medical decision-making. The methods include hierarchical models, models informed by evidence on different functions of several parameters and models incorporating both of these features. The need to check for consistency of evidence when using these powerful methods is emphasized. We develop a rationale for evidence synthesis that is based on Bayesian decision modelling and expected value of information theory, which stresses not only the need for a lack of bias in estimates of treatment effects but also a lack of bias in assessments of uncertainty. The increasing reliance of governmental bodies like the UK National Institute for Clinical Excellence on complex evidence synthesis in decision modelling is discussed.     

Bayesian inference for generalized additive mixed models based on Markov random field priors

Most regression problems in practice require flexible semiparametric forms of the predictor for modelling the dependence of responses on covariates. Moreover, it is often necessary to add random effects accounting for overdispersion caused by unobserved heterogeneity or for correlation in longitudinal or spatial data. We present a unified approach for Bayesian inference via Markov chain Monte Carlo simulation in generalized additive and semiparametric mixed models. Different types of covariates, such as the usual covariates with fixed effects, metrical covariates with non-linear effects, unstructured random effects, trend and seasonal components in longitudinal data and spatial covariates, are all treated within the same general framework by assigning appropriate Markov random field priors with different forms and degrees of smoothness. We applied the approach in several case-studies and consulting cases, showing that the methods are also computationally feasible in problems with many covariates and large data sets. In this paper, we choose two typical applications.     

Recovering Information from Incremental Responses

Some yields analysed and reported in the literature have been adjusted by subtracting a control. It is found that full information can be recovered for estimable parameters and the error variance using these incremental responses, in comparison with unadjusted data. These findings are of practical importance, and they supplement materials usually found in a graduate course in linear inference. The issues are illustrated using a case study from the literature.     

Analysis of incomplete durations with application to contraceptive use

Models for analysing incomplete durations obtained from cross-sectional surveys are presented. The aim of the paper is to develop a framework for analysing the incomplete duration of episodes in progress at the time of the survey by formulating generalized linear models and fitting and assessing them by using standard statistical packages. The maximum quasi-likelihood method is used for model fitting. The choice of the distribution and the diagnostic procedures are discussed. Simulated data from two distributions (the Weibull and log-logistic distributions) are used to evaluate the methodology developed and to assess model misspecifications. A data set on the current use of the contraceptive pill from a cross-sectional survey in Egypt is analysed.