Hybrid (Symbolic-Numerical) Optimization in Mechanism Design for the Elimination of Redundant Constraints

Introduction Today, one of the challenges of computer-based optimization lies in the application of artificial intelligence (AI) principles to the creation of systematic and well-structured design procedures Universal joints are used extensively to couple misaligned power shafts. Mazziotti [14] presents a discussion of some o

2016 ACR-EULAR adult dermatomyositis and polymyositis and juvenile dermatomyositis response criteria-methodological aspects

Objective. The objective was to describe the methodology used to develop new response criteria for adult DM/PM and JDM. Methods. Patient profiles from prospective natural history data and clinical trials were rated by myositis specialists to develop consensus gold-standard ratings of minimal, moderate and major improvement. Experts completed a survey regarding clinically meaningful improvement in the core set measures (CSM) and a conjoint-analysis survey (using 1000Minds software) to derive relative weights of CSM and candidate definitions. Six types of candidate definitions for response criteria were derived using survey results, logistic regression, conjoint analysis, application of conjoint-analysis weights to CSM and published definitions. Sensitivity, specificity and area under the curve were defined for candidate criteria using consensus patient profile data, and selected definitions were validated using clinical trial data. Results. Myositis specialists defined the degree of clinically meaningful improvement in CSM for minimal, moderate and major improvement. The conjoint-analysis survey established the relative weights of CSM, with muscle strength and Physician Global Activity as most important. Many candidate definitions showed excellent sensitivity, specificity and area under the curve in the consensus profiles. Trial validation showed that a number of candidate criteria differentiated between treatment groups. Top candidate criteria definitions were presented at the consensus conference. Conclusion. Consensus methodology, with definitions tested on patient profiles and validated using clinical trials, led to 18 definitions for adult PM/DM and 14 for JDM as excellent candidates for consideration in the final consensus on new response criteria for myositis

Influence of the entorhinal cortex on accumbal and striatal dopaminergic responses in a latent inhibition paradigm

International audienceThe use of latent inhibition paradigms is one means of investigating the involvement of mesencephalic dopaminergic (DA) neurons in cognitive processes. We have shown recently that DA neurons reaching the core and the dorsomedial shell parts of the nucleus accumbens and the anterior part of the striatum are differentially involved in latent inhibition. In other respects, theoretical, behavioral and anatomo-functional data suggest that the entorhinal cortex (ENT) may control latent inhibition expression. In this study, using in vivo voltammetry in freely moving rats, we investigated the influence of the ENT on the DA responses obtained in the core and dorsomedial shell parts of the nucleus accumbens and the anterior part of the striatum. For this purpose a reversible inactivation of the left ENT was achieved by the local microinjection of tetrodotoxin, 3 h before pre-exposure to the conditional stimulus (banana odour). During the second session, animals were aversively conditioned to banana odour. Results obtained during the third session (test session), in animals submitted to the reversible blockade of the ENT before the first session were as follows: (1) pre-exposed conditioned animals displayed behavioral aversive responses; (2) where core DA responses were concerned, responses were situated between those observed in pre-exposed and non-pre-exposed conditioned animals; (3) by contrast, where the dorsomedial shell part of the nucleus accumbens and the anterior striatum were concerned, DA variations were not statistically different in pre-exposed and non-pre-exposed conditioned rats. These data suggest that the left ENT exerts a crucial influence over the latent-inhibition-related DA responses in the left dorsomedial shell part of the nucleus accumbens and the left anterior part of the striatum, whereas one or more other brain regions control DA variations in the left core part of the nucleus accumbens. These data may help us to understand the pathophysiology of schizophrenic psychoses