Les idéalistes britanniques et la poésie

Cet article explore la conception que les idéalistes britanniques se firent de la relation entre la philosophie et la poésie. J’examine la classification proposée par Hegel ainsi que la façon dont ils la modifièrent, et les difficultés auxquelles ils firent face dans leur tentative d’accommoder les critiques bien connues de Platon. J’examine ensuite certaines critiques adressées aux idéalistes à partir du point de vue de la philosophie analytique pour en conclure qu’elles ne sont guère convaincantes.This article explores the relation between philosophy and poetry according to the British Idealists. I examine their place in Hegel’s classification as they modified it and the difficulties that they faced when trying to accommodate Plato’s well-known criticisms. I examine further some of the criticisms of the British Idealist conceptions from the standpoint of Analytic Philosophy, in order to show how inconclusive they are

Further investigations into the preparation and [4+2] cycloaddition reactions of vinyl norcaradiene derivatives

Copyright © ARKAT USA, Inc The document attached has been archived with permission from the publisher.Norcaradiene derivatives derived from the copper-catalyzed intramolecular cyclopropanation reactions of 2-(5-vinyl-1,2,3,4-tetrahydronaphthalene) diazomethyl ketones have been prepared and submitted to Diels–Alder reactions with a range of dienophiles, including methyl acrylate, methyl 2-chloroacrylate, maleic anhydride and citraconic anhydride. The cycloaddition reactions gave better yields and were more selective when the vinyl norcaradienes were based on 8-methoxynaphthyl diazoketones.Lisa A. Buttle, Jonathan C. Morris, and Lewis N. Mande

A product of independent beta probabilities dose escalation design for dual-agent phase I trials.

Dual-agent trials are now increasingly common in oncology research, and many proposed dose-escalation designs are available in the statistical literature. Despite this, the translation from statistical design to practical application is slow, as has been highlighted in single-agent phase I trials, where a 3 + 3 rule-based design is often still used. To expedite this process, new dose-escalation designs need to be not only scientifically beneficial but also easy to understand and implement by clinicians. In this paper, we propose a curve-free (nonparametric) design for a dual-agent trial in which the model parameters are the probabilities of toxicity at each of the dose combinations. We show that it is relatively trivial for a clinician's prior beliefs or historical information to be incorporated in the model and updating is fast and computationally simple through the use of conjugate Bayesian inference. Monotonicity is ensured by considering only a set of monotonic contours for the distribution of the maximum tolerated contour, which defines the dose-escalation decision process. Varied experimentation around the contour is achievable, and multiple dose combinations can be recommended to take forward to phase II. Code for R, Stata and Excel are available for implementation.We would like to acknowledge funding from the UK Medical Research Council (grant code U1052.00.014) for this work. We would also like to thank the reviewers for providing some excellent suggestions to help improve the manuscript.This is the final published version. It first appeared at http://onlinelibrary.wiley.com/doi/10.1002/sim.6434/abstract

Do single-arm trials have a role in drug development plans incorporating randomised trials?

Often, single-arm trials are used in phase II to gather the first evidence of an oncological drug's efficacy, with drug activity determined through tumour response using the RECIST criterion. Provided the null hypothesis of 'insufficient drug activity' is rejected, the next step could be a randomised two-arm trial. However, single-arm trials may provide a biased treatment effect because of patient selection, and thus, this development plan may not be an efficient use of resources. Therefore, we compare the performance of development plans consisting of single-arm trials followed by randomised two-arm trials with stand-alone single-stage or group sequential randomised two-arm trials. Through this, we are able to investigate the utility of single-arm trials and determine the most efficient drug development plans, setting our work in the context of a published single-arm non-small-cell lung cancer trial. Reference priors, reflecting the opinions of 'sceptical' and 'enthusiastic' investigators, are used to quantify and guide the suitability of single-arm trials in this setting. We observe that the explored development plans incorporating single-arm trials are often non-optimal. Moreover, even the most pessimistic reference priors have a considerable probability in favour of alternative plans. Analysis suggests expected sample size savings of up to 25% could have been made, and the issues associated with single-arm trials avoided, for the non-small-cell lung cancer treatment through direct progression to a group sequential randomised two-arm trial. Careful consideration should thus be given to the use of single-arm trials in oncological drug development when a randomised trial will follow.Michael J. Grayling is supported by the Wellcome Trust [grant number 099770/Z/12/Z]. Adrian P. Mander is supported by the Medical Research Council [grant number G0800860].This is the final version of the article. It first appeared from Wiley via http://dx.doi.org/10.1002/pst.172

Damage avoidance design steel beam-column moment connection using high-force-to-volume dissipators

Existing welded steel moment frames are designed to tolerate substantial yielding and plastic rotation under earthquake loads. This sacrificial design approach can lead to permanent, and often irreparable damage when interstory drifts exceed 2%. The experimental seismic performance of a 50% full-scale damage avoidance designed structural steel beam-column connection is presented. The beam-column joint region consists of a top flange-hung beam connected to the column by an angle bracket. High-force-to-volume (HF2V) devices are attached from the column to the beam to provide joint rigidity and energy dissipation as the joint opens and closes. The HF2V devices are connected either below the beam flange or concealed above the beam's lower flange. Reversed cyclic lateral load tests are conducted with drift amplitudes up to 4%. No damage is observed in the principal beam and column structural elements. The need for stiff device connections to achieve optimal device performance is demonstrated, and potential design solutions presented. Stable hysteresis and repeatable energy dissipation for a large number of cycles up to the 4% drift level is observed. It is concluded that superior and repeatable energy dissipation without damage can be achieved for every dynamic motion cycle, in contrast to conventional sacrificially designed welded moment frame connections

Understanding jumping to conclusions in patients with persecutory delusions: working memory and intolerance of uncertainty

Background. Persecutory delusions are a key psychotic experience. A reasoning style known as ‘jumping to conclusions’ (JTC) – limited information gathering before reaching certainty in decision making – has been identified as a contributory factor in the occurrence of delusions. The cognitive processes that underpin JTC need to be determined in order to develop effective interventions for delusions. In the current study two alternative perspectives were tested: that JTC partially results from impairment in information-processing capabilities and that JTC is a motivated strategy to avoid uncertainty.Method. A group of 123 patients with persistent persecutory delusions completed assessments of JTC (the 60:40 beads task), IQ, working memory, intolerance of uncertainty, and psychiatric symptoms. Patients showing JTC were compared with patients not showing JTC.Results. A total of 30 (24%) patients with delusions showed JTC. There were no differences between patients who did and did not jump to conclusions in overall psychopathology. Patients who jumped to conclusions had poorer working memory performance, lower IQ, lower intolerance of uncertainty and lower levels of worry.Working memory and worry independently predicted the presence of JTC.Conclusions. Hasty decision making in patients with delusions may partly arise from difficulties in keeping information in mind. Interventions for JTC are likely to benefit from addressing working memory performance, while in vivo techniques for patients with delusions will benefit from limiting the demands on working memory. The study provides little evidence for a contribution to JTC from top down motivational beliefs about uncertainty

Group sequential designs for stepped-wedge cluster randomised trials.

BACKGROUND/AIMS: The stepped-wedge cluster randomised trial design has received substantial attention in recent years. Although various extensions to the original design have been proposed, no guidance is available on the design of stepped-wedge cluster randomised trials with interim analyses. In an individually randomised trial setting, group sequential methods can provide notable efficiency gains and ethical benefits. We address this by discussing how established group sequential methodology can be adapted for stepped-wedge designs. METHODS: Utilising the error spending approach to group sequential trial design, we detail the assumptions required for the determination of stepped-wedge cluster randomised trials with interim analyses. We consider early stopping for efficacy, futility, or efficacy and futility. We describe first how this can be done for any specified linear mixed model for data analysis. We then focus on one particular commonly utilised model and, using a recently completed stepped-wedge cluster randomised trial, compare the performance of several designs with interim analyses to the classical stepped-wedge design. Finally, the performance of a quantile substitution procedure for dealing with the case of unknown variance is explored. RESULTS: We demonstrate that the incorporation of early stopping in stepped-wedge cluster randomised trial designs could reduce the expected sample size under the null and alternative hypotheses by up to 31% and 22%, respectively, with no cost to the trial's type-I and type-II error rates. The use of restricted error maximum likelihood estimation was found to be more important than quantile substitution for controlling the type-I error rate. CONCLUSION: The addition of interim analyses into stepped-wedge cluster randomised trials could help guard against time-consuming trials conducted on poor performing treatments and also help expedite the implementation of efficacious treatments. In future, trialists should consider incorporating early stopping of some kind into stepped-wedge cluster randomised trials according to the needs of the particular trial