Marginal and association regression models for longitudinal binary data with drop‐outs: A likelihood‐based approach

Longitudinal data often contain missing observations, and it is in general difficult to justify particular missing data mechanisms, whether random or not, that may be hard to distinguish. The authors describe a likelihood‐based approach to estimating both the mean response and association parameters for longitudinal binary data with drop‐outs. They specify marginal and dependence structures as regression models which link the responses to the covariates. They illustrate their approach using a data set from the Waterloo Smoking Prevention Project They also report the results of simulation studies carried out to assess the performance of their technique under various circumstances.     

Proportional reversed hazard rate model and its applications

The purpose of this paper is to study the structure and properties of the proportional reversed hazard rate model (PRHRM) in contrast to the celebrated proportional hazard model (PHM). The monotonicity of the hazard rate and the reversed hazard rate of the model is investigated. Some criteria of aging are presented and the inheritance of the aging notions (of the base distribution) by the PRHRM is studied. Characterizations of the model involving Fisher information are presented and the statistical inference of the parameters is discussed. Finally, it is shown that several members of the proportional reversed hazard rate class have been found to be useful and flexible in real data analysis.     

Horwitz's rule, transforming both sides and the design of experiments for mechanistic models

Summary. The paper develops methods for the design of experiments for mechanistic models when the response must be transformed to achieve symmetry and constant variance. The power transformation that is used is partially justified by a rule in analytical chemistry. Because of the nature of the relationship between the response and the mechanistic model, it is necessary to transform both sides of the model. Expressions are given for the parameter sensitivities in the transformed model and examples are given of optimum designs, not only for single-response models, but also for experiments in which multivariate responses are measured and for experiments in which the model is defined by a set of differential equations which cannot be solved analytically. The extension to designs for checking models is discussed.     

Causal inference with generalized structural mean models

Summary.  We estimate cause–effect relationships in empirical research where exposures are not completely controlled, as in observational studies or with patient non-compliance and self-selected treatment switches in randomized clinical trials. Additive and multiplicative structural mean models have proved useful for this but suffer from the classical limitations of linear and log-linear models when accommodating binary data. We propose the generalized structural mean model to overcome these limitations. This is a semiparametric two-stage model which extends the structural mean model to handle non-linear average exposure effects. The first-stage structural model describes the causal effect of received exposure by contrasting the means of observed and potential exposure-free outcomes in exposed subsets of the population. For identification of the structural parameters, a second stage 'nuisance' model is introduced. This takes the form of a classical association model for expected outcomes given observed exposure. Under the model, we derive estimating equations which yield consistent, asymptotically normal and efficient estimators of the structural effects. We examine their robustness to model misspecification and construct robust estimators in the absence of any exposure effect. The double-logistic structural mean model is developed in more detail to estimate the effect of observed exposure on the success of treatment in a randomized controlled blood pressure reduction trial with self-selected non-compliance.     

Boundary Spaces

While shows like The X-Files and 24 have merged conspiracy theories with popular science (fictions), some video games have been pushing the narrative even further. Electronic Art's Majestic game was released in July 2001 and quickly generated media buzz with its unusual multi-modal gameplay. Mixing phone calls, faxes, instant messaging, real and "fake' websites, and email, the game provides a fascinating case of an attempt at new directions for gaming communities. Through story, mode of playing, and use of technology, Majestic highlights the uncertain status of knowledge, community and self in a digital age; at the same time, it allows examination of alternative ways of understanding games' role and purpose in the larger culture. Drawing on intricate storylines involving government conspiracies, techno-bio warfare, murder and global terror, players were asked to solve mysteries in the hopes of preventing a devastating future of domination. Because the game drew in both actual and Majestic-owned/-designed websites, it constantly pushed those playing the game right to borders where simulation collides with " factuality'. Given the wide variety of "legitimate' conspiracy theory, alien encounters and alternative science web pages, users often could not distinguish when they were leaving the game's pages and venturing into " real' World Wide Web sites. Its further use of AOL's instant messenger system, in which gamers spoke not only to bots but to other players, pushed users to evaluate constantly both the status of those they were talking to and the information being provided. Additionally, the game required players to occupy unfamiliar subject positions, ones where agency was attenuated, and which subsequently generated a multi-layered sense of unease among players. This mix of authentic and staged information in conjunction with technologically mediated roles highlights what are often seen as phenomenon endemic to the Internet itself; that is, the destabilization of categories of knowing, relating, and being.     

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.     

Measuring Substance Abuse Treatment Need Among Adults in Florida: A Social Indicators Approach

Determining the size and demographiccharacteristics of substance abuse populationsis extremely important for implementing publicpolicies aimed at the control of substanceabuse. Such information not only assists in theallocation of limited treatment resources bythe state, but also in the monitoring ofsubstance abuse trends over time and in theevaluation of innovative policy initiatives. Inthis study, we develop three composite measuresof treatment need. We then use these measuresto estimate treatment need for alcohol abuseand for controlled substance abuse within eachof Florida's 67 counties. This study providesan important empirical component of communityplanning, quantifying and, to a limited degree,specifying the level of need for the substanceabuse treatment of community residents. Anadditional benefit is the development of a costeffective and unobtrusive methodology fordetermining empirically when levels of need arechanging so that treatment levels can beadjusted accordingly. With proper use,policymakers can readily employ the methodologydeveloped in this study in Florida andelsewhere to make better-informed decisions inthe allocation of finite substance abusetreatment resources.