Models of Neurotoxicity: Extrapolation of Benchmark Doses in Vitro

In risk assessment, no observed exposure level (NOAEL) and benchmark dose (BMD) are usually derived either from epidemiological studies in humans or from animal experiments. In many in vitro studies, concentration-effect/response curves have been analyzed using different mathematical models finalized to the identification of EC50. In the present article, we propose a model to fit dose-response curves in vitro. The BMD approach has been used to compare the cell viability (MIT assay) of different rat (C6 and PC12, glial and neuronal, respectively) and human cell lines (D384 and SK-N-MC, glial and neuronal, respectively) after 24-hour exposure to the following neurotoxic substances: manganese chloride (MnCl2), methyl-mercury (Me-Hg), and the enantiomers of styrene oxide (SO). For all rat and human cell lines, the potency of the examined compounds was: MnCl2 < S-SO < R-SO < Me-Hg. A preliminary comparison with in vivo toxicity data for these substances gave rise to consistent results. Whereas a reasonable agreement between in vitro and in vivo data has been found for Mn and styrene oxide, a wide scatter of LOAEL has been reported for Me-Hg and these appear to be either much higher or lower than the BMD for the MIT assay we observed in vitro.     

The Origin,Development, and Contemporary Status of Critical Theory*

This paper describes the nature of critical theory, its historical development, its connections to sociology and Marxism, and the central debates over its core ideas.     

Tree-structured subgroup analysis for censored survival data: Validation of computationally inexpensive model selection criteria

The performance of computationally inexpensive model selection criteria in the context of tree-structured subgroup analysis is investigated. It is shown through simulation that no single model selection criterion exhibits a uniformly superior performance over a wide range of scenarios. Therefore, a two-stage approach for model selection is proposed and shown to perform satisfactorily. Applied example of subgroup analysis is presented. Problems associated with tree-structured subgroup analysis are discussed and practical solutions are suggested.     

Strong formulation for the spot 5 daily photograph scheduling problem

Earth observation satellites, such as the SPOT 5, take photographs of the earth according to consumers’ demands. Obtaining a good schedule for the photographs is a combinatorial optimization problem known in the literature as the daily photograph scheduling problem (DPSP). The DPSP consists of selecting a subset of photographs, from a set of candidates, to different cameras, maximizing a profit function and satisfying a large number of constraints. Commercial solvers, with standard integer programming formulations, are not able to solve some DPSP real instances available in the literature. In this paper we present a strengthened formulation for the DPSP, based on valid inequalities arising in node packing and 3-regular independence system polyhedra. This formulation was able, with a commercial solver, to solve to optimality all those instances in a short computation time.     

Design of Stockless Production Systems

In make‐to‐stock production systems finished goods are produced in anticipation of demand. By contrast, in stockless production systems finished goods are not produced until demand is observed. In this study we investigate the problem of designing a multi‐item manufacturing system, where there is both demand‐ and production‐related uncertainty, so that stockless operation will be optimal for all items. For the problem of interest, we focus on gaining an understanding of the effect of two design variables: (i) manufacturing speed—measured by the average manufacturing rate or, equivalently, the average unit manufacturing time, and (ii) manufacturing consistency—measured by the variation in unit manufacturing times. We establish conditions on these two variables that decision makers can use to design stockless production systems. Managerial implications of the conditions are also discussed.     

A Robust Procedure in Nonlinear Models for Repeated Measurements

Nonlinear regression models arise when definite information is available about the form of the relationship between the response and predictor variables. Such information might involve direct knowledge of the actual form of the true model or might be represented by a set of differential equations that the model must satisfy. We develop M-procedures for estimating parameters and testing hypotheses of interest about these parameters in nonlinear regression models for repeated measurement data. Under regularity conditions, the asymptotic properties of the M-procedures are presented, including the uniform linearity, normality and consistency. The computation of the M-estimators of the model parameters is performed with iterative procedures, similar to Newton–Raphson and Fisher's scoring methods. The methodology is illustrated by using a multivariate logistic regression model with real data, along with a simulation study.     

Standard Exponential Cure Rate Model with Informative Censoring

In this article, we consider the standard cure rate model proposed by Boag (1949 Boag , J. W. ( 1949 ). Maximum likelihood estimates of the proportion of patients cured by cancer therapy . J. Roy. Statist. Soc. B 11 : 15 – 53 . [Google Scholar]) and Berkson and Gage (1952 Berkson , J. , Gage , R. ( 1952 ). Survival curve for cancer patients following treatment . J. Amer. Statist. Assoc. 47 : 501 – 515 .[Taylor & Francis Online], [Web of Science ®] , [Google Scholar]). We present a new definition of informative censoring similar to Lawless (1982 Lawless , J. F. ( 1982 ). Statistical Models and Methods for Lifetime Data . New York : Wiley .[Crossref] , [Google Scholar]) and the corresponding likelihood function. Under informative censoring, we obtain the Fisher information matrix of the exponential standard cure rate model. We verify, with simulated data, the impact caused by informative censoring in the coverage probabilities and in the lengths of asymptotic confidence intervals of the parameters of interest. An example with real data is analyzed.     

Lower posterior death probabilities from a quick medical response in road traffic accidents

Introduction: We use data from Spain on roads and motorways traffic accidents in May 2004 to quantify the statistical association between quick medical response time and mortality rate. Method: Probit and logit parameters are estimated by a Bayesian method in which samples from the posterior densities are obtained through an MCMC simulation scheme. We provide posterior credible intervals and posterior partial effects of a quick medical response at several time levels over which we express our prior beliefs. Results: A reduction of 5 min, from a 25-min response-time level, is associated with lower posterior probabilities of death in roads and motorways accidents of 24% and 30%, respectively.     

Learning in and from projects: the learning modes and a learning capability model

Abstract

The notion of ‘project delivery’ is well embedded in and across the management and organizational sciences literature – generating a narrative that reflects and recognizes the instrumental nature of projects and programmes in strategy execution. Project management, as a distinct and well-established body of research enquiry, has increasingly sought to focus our attention on the impacts of complexity, risk and uncertainty in projects; the corollary being a desideratum to strengthen our theoretical understanding of how insight and learning from projects may influence improvements to organizational efficiency. The wider literature suggests that organizational learning remains a challenging proposition, particularly in the context of organizations operating in environments of high complexity. In this paper, we enhance the conversation on organizational learning through a series of case studies, generating evidence of thirteen ‘learning modes’. The paper proposes that mature organizations tend to exhibit a greater number of learning modes and that there is a tendency to capture and socialize knowledge with a greater emphasis on the context of the learning situation rather than the learning artefact in isolation. The empirical evidence gathered in this paper forms the basis of a capability model, characterized by the thirteen modes of learning. The model intimates that learning occurs, and is more effective, when knowledge and information are enacted in practice through the learning modes which form a nucleus of the organizational learning capability. The research concludes with a 'call to action' that emphasizes the strategic importance of learning practices and routines in project oriented-organizations.     

The roles of supply network centralities in firm performance and the moderating effects of reputation and export-orientation

Abstract

This study explores how supply network degree, closeness, and betweenness centralities affect firm performance, and the moderating effects of organizational reputation (measured by PageRank centrality) and export-orientation. The supply chain relationship empirical data are drawn from manufacturing and manufacturing service companies in Hong Kong, China. Social network analysis and moderated regression analysis were adopted to test the hypotheses for a sample of 814 focal firms with 3086 supply chain ties. The results indicate that in-degree and closeness centralities improve firm performance. Reputation is found to positively moderate the relationship between closeness and sales performance, but negatively moderates the relationship between betweenness and sales performance. Export-orientation has no effect on relationships. This study contributes to the literature by providing additional empirical evidence on the role of supply network position in firm performance. It also introduces PageRank centrality as a new measure of organizational reputation in a supply network.