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)

This is the text of The Lindley Lecture for 1996, given by T.M. Scanlon, an American philosopher.

We introduce a simple model for so-called spin-echo experiments. We show that the model is a mincing system. On the basis of this model we study fine-grained entropy and coarse-grained entropy descriptions of these experiments. The coarse-grained description is shown to be unable to provide an explanation of the echo signals, as a result of the way in which it ignores dynamically generated correlations. This conclusion is extended to the general debate on the foundations of statistical mechanics. We emphasize the (...) need for an appropriate mechanism to explain the gradual suppression over time of the correlations in a thermodynamic system. We argue that such a mechanism can only be provided by the interventionist approach, in which the interaction of the system with its environment is taken into account. Irreversible behavior is then seen to arise not as a result of limited measurement accuracy , but as a result of the fact that thermodynamic systems are limited systems which interact with their environment. A detailed discussion is given of recent objections to the interventionist approach in the literature. (shrink)

Modern commentators like Allen Wood have noted that for Kant there “is a basic tension in human nature between loving people and respecting them.” Love is a threat to pure morality insofar as love is an empirical inclination and any will determined by such an inclination is unfree. In this paper, I begin by exploring why Kant thinks that love is a threat to moral freedom. Drawing on the insights of Dietrich von Hildebrand, I propose instead an analysis of love (...) as “value-response.” I argue that a more complete phenomenological analysis of the nature of human affectivity (as fundamentally intentional and responsive) exposes a serious defect in Kant’s moral psychology, particularly his unreasonable denial of the compatibility of higher-order affectivity and human freedom. Drawing on von Hildebrand’s notion of “cooperative freedom,” I argue that not only is a higher-order spiritual affectivity compatible with freedom and morality, but it is essential to it. (shrink)