Pancreatitis is a complex, progressively destructive inflammatory disorder. Alcohol was long thought to be the primary causative agent, but genetic contributions have been of interest since the discovery that rare PRSS1, CFTR and SPINK1 variants were associated with pancreatitis risk. We now report two associations at genome-wide significance identified and replicated at PRSS1-PRSS2 and X-linked CLDN2 through a two-stage genome-wide study. The PRSS1 variant likely affects disease susceptibility by altering expression of the primary trypsinogen gene. The CLDN2 risk allele is (...) associated with atypical localization of claudin-2 in pancreatic acinar cells. The homozygous CLDN2 genotype confers the greatest risk, and its alleles interact with alcohol consumption to amplify risk. These results could partially explain the high frequency of alcohol-related pancreatitis in men. © 2012 Nature America, Inc. All rights reserved. (shrink)

Il est une question fondamentale dont il semble pourtant qu’elle n’ait pas été posée: celle de savoir ce qui fait que le cogito soit effectivement un principe métaphysique, c’est-à-dire une vérité première. Il semble aussi que ce qui d’ordinaire tient lieu de réponse à cette question dans l’esprit des lecteurs de Descartes, c’est le sentiment vague qu’il s’agit là de la première vérité qui surgisse après la dévastation laissée par le doute universel de la Première Méditation, ou peut-être qui surgisse (...) au cœur de ce doute, puisque le doute ne s’autodétruit que pour faire place à ego sumOr s’en tenir à cela pour justifier le statut de principe métaphysique du cogito, c’est confondre priorité chronologique et primauté métaphysique ou épistémique: en effet, qu’y aurait-il dans le seul fait de se présenter ainsi qui assure que le cogito doive fonder d’autres connaissances, d’éventuelles sciences? Qu’est-ce qui empêcherait aussi qu’il ne soit lui-même assujetti à d’autres connaissances, plus fondamentales, et dont le méditant ne se serait peut-être pas encore aperçu? Il est vrai que cette confusion est compréhensible, puisque la primauté métaphysique du cogito coïncide effectivement avec sa priorité dans l’ordre des connaissancesMais dans le doute ambiant, celle-ci n’est en réalité qu’un effet de celle-là, et le simple fait de constater l’une ne revient pas à être assuré de l’autre. Il ne peut s’agir donc que d’une coïncidence, et la question se pose dès lors de savoir comment se traduit sa primauté, c’est-à-dire comment doivent se concevoir ses rapports avec le reste de nos éventuelles connaissances. (shrink)

We consider the potential impact of Computer Supported Cooperative Work, with special reference to large technically advanced projects involving several organizations. It is vital that such projects are managed efficiently, without delays, since a product that reaches the market a few months earlier than its competitors enjoys a great advantage. Traditional methods of coordinating large projects, based on hierarchical communication, tend to produce delays, since technicians at remote sites are obliged to solve coordination problems by passing them up the hierachy. (...) It would be better if such problems were solved by improvising conferences among the technicians; Computer Supported Cooperative Work will provide the technical means of implementing this heterarchical style of management without losing control of the project. The use of computers as a social medium raises methodological and ethical issues which are discussed in the final section. (shrink)

The question of the dimensionality of space has informed the development of physics since the beginning of the twentieth century in the quest for a unified picture of quantum processes and gravitation. Scientists have worked within various approaches to explain why the universe appears to have a certain number of spatial dimensions. The question of why space has three dimensions has a genuinely philosophical nature that can be shaped as a problem of justifying a contingent necessity of the world. In (...) contrast to explanations of three-dimensionality based on anthropic arguments, we support the search for a theory that provides a justification for the dimensionality of space based on a combination of deductive and inductive reasoning applied to science. In doing so, we argue that Kant correctly approached the question in “Thoughts on the true estimation of living forces” by connecting space dimensionality and the inverse square law. In expounding the strategy of Kant’s argument, we describe the main features of a general Kantian explanation of the dimensionality of space and discuss them with respect to current accounts of explanation in the philosophy of science, such as inference to the best explanation and the deductive-nomological model. (shrink)

In dieser Aufsatzsammlung wird Johann Georg Hamanns Grundthese von Gott als Schriftsteller interpretiert und in weitest reichende literarische Zusammenhange gestellt. Der Zusammenhang von Reden, Horen und Sehen wird theologisch und eschatologisch untersucht. Hamanns Gedanken zum Abendmahl und Sacrament der Sprache werden mit der Rolle des Essens und Trinkens in Beziehung gebracht. Die Narziss-Episode der Metamorphosen des Ovid deutete der Schriftsteller christologisch und als Kenner des Hebraerbriefs verfasste er eine kritische Rezension des Kommentars von J. D. Michaelis (Gottingen). Der Autor (...) arbeitet die Bedeutung Hamanns als der massgebliche theologische Sprachdenker nach Luther heraus, dessen Worttheologie u. a. Kierkegaard gepragt hat. (shrink)

J D Marshall; Thomas Hobbes: education and obligation in the Commonwealth, Journal of Philosophy of Education, Volume 14, Issue 2, 30 May 2006, Pages 193–203, h.

Scientists and laypeople alike use the sense of understanding that an explanation conveys as a cue to good or correct explanation. Although the occurrence of this sense or feeling of understanding is neither necessary nor sufficient for good explanation, it does drive judgments of the plausibility and, ultimately, the acceptability, of an explanation. This paper presents evidence that the sense of understanding is in part the routine consequence of two well-documented biases in cognitive psychology: overconfidence and hindsight. In light of (...) the prevalence of counterfeit understanding in the history of science, I argue that many forms of cognitive achievement do not involve a sense of understanding, and that only the truth or accuracy of an explanation make the sense of understanding a valid cue to genuine understanding. (shrink)