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)

David Lewis has complained about the truthmaker theory as a version of the correspondence theory of truth (Lewis 2001a; Lewis 2001b). His main criticism is that the truthmaker theory, if combined with the redundancy theory, is not a theory about truth, but only »about the existential grounding of all manner of other things: the flying of pigs, or what-have-you« (Lewis 2001a: 279; Lewis 2001b: 603-4). In his view, to call such a truthmaker theory a theory (...) of truth is a »misnomer« (Lewis 2001a: 279). Lewis does not claim that the truthmaker theory is false, nor does he reject it. Indeed, he expresses agreement with its spirit. But of course it would be an embarrassment to any defender of the truthmaker theory to find out that it is not about truth at all. Indeed, if it were not about truth we should »forget about the ´correspondence theory of truth´«, as the title of Lewis´ paper suggests. Therefore, it is highly desirable for any adherent of the truthmaker theory to look for an understanding of the truthmaker theory which will let it be about truth, and to see whether anything of what Lewis has said provides an argument against it. We will argue that there is such an understanding and that Lewis has not provided any material for an argument against it. (shrink)

Frank and Nagel are very interested in the causes and consequences of moralizing about addiction. If addiction is a disease, moralistic concerns are sidelined. If it's a choice, we'd better identify clear reasons to absolve addicts from blame. While these are interesting considerations, they don't have much to do with the model of addiction I put forward in the target article.

In lieu of an abstract, here is a brief excerpt of the content:Reviewed by:A Search for Unity in Diversity: The "Permanent Hegelian Deposit" in the Philosophy of John DeweyFrank X. RyanJames A. Good A Search for Unity in Diversity: The "Permanent Hegelian Deposit" in the Philosophy of John Dewey Lanham, MD: Lexington Books, 2006. xxx + 288 pp.Among the revelations of Dewey's rare moments of autobiographical reflection, none has generated more curiosity and investigative zeal than his 1930 claim to have (...) "drifted" from Hegel in the decade following his move from Michigan to Chicago in 1894. Beginning with Morton White's Origin of Dewey's Instrumentalism (1943), biographers have divided on the question of whether Dewey's later philosophy was more strongly influenced by William James's experimental psychology or F. J. E. Woodbridge's Aristotelian naturalism. Despite their differences, both approaches are essentially empirical and realistic, and thus the majority of sympathetic commentators have agreed that Dewey was a realist, albeit of a decidedly unorthodox stripe. For them the notion that Dewey retained any significant commitment to idealism, given its virtual eradication at the beginning of the twentieth century, would damage his influence and legacy.It has been something of a puzzle, accordingly, that in the same autobiographical essay Dewey alludes to a "permanent Hegelian deposit." For years Richard Rorty has claimed this differentiates a "good" Dewey committed to "social flourishing" from a "bad" Dewey prone to metaphysical dalliance. But the first systematic inquiry into Dewey's enduring Hegelianism is John R. Shook's Dewey's Empirical Theory of Knowledge and Reality (2000). Shook argues convincingly that Dewey never abandoned idealism, but rather transformed it into an experimental naturalism by doing away with both "mind-stuff" and equally noxious "things-in-themselves." In many ways James Good's A Search for Unity in Diversity is a bookend to Shook's project, though Good further differentiates Anglo-American Neo-Hegelianism from Hegel himself. According to Good, Dewey endorsed a Humanistic/Historicist interpretation of Hegel rooted in the reciprocal engagement of individuals and societies, rather than the supernatural and architectonic absolute championed by Neo-Hegelians such as T. H. Green, and F. H. Bradley. With [End Page 216] top-notch scholarship and scrupulous attention to detail, A Search for Unity in Diversity is both an excellent intellectual biography and a penetrating plea for a radical reinterpretation of Dewey's contribution to philosophy. I'll briefly sketch the historical account before addressing the more controversial claims about the "permanent Hegelian deposit."Even readers familiar with the half-dozen book-length treatments of Dewey's development will find this account refreshing and informative. Good's professional credentials as a historian shine as he recreates the rough and bustling Burlington of Dewey's youth. In the 1870s, German idealism was considered the epitome of political liberalism and progressive education, and Dewey's journey toward the "inclusive philosophical idea" of the social began in an environment swirling with the crosscurrents of Kant, Hegel, and Schelling. At the White Street Congregational Church, Lewis Barstow preached a liberal orthodoxy that was essentially "man-building" (102), and Good presents a convincing case for the likelihood that even in boyhood Dewey never viewed God as an aloof law-giver or cosmic architect, but as a process unifying the individual and the social within a natural world of unlimited potential. At the University of Vermont Dewey encountered a struggling rural college transformed into the first bastion of American transcendentalism by James Marsh, who inspired a "Burlington philosophy" that rejected atomistic empiricism for a holistic integrity of knowing and doing, facts and values, and pure and practical reasons (57–59).In noting the influence of the "St. Louis Hegelians" upon Dewey, most biographers have focused on W. T. Harris, the prominent founder of The Journal of Speculative Philosophy who published Dewey's earliest submissions and offered encouragement that led to his pursuit of graduate work at Johns Hopkins. Good augments this familiar tale with fascinating depictions of equally influential yet lesser-known Hegelians such as H. C. Brokmeyer, Denton Snider, and Thomas Davidson. At a time when European Hegelianism was polarized between, on the one hand, reactionary apologists for traditional Christianity and Prussian militarism and, on the other, radical... (shrink)

Although the notion of spatiality has always lurked in the background of discussions of literary form, the self-conscious use of the term as a critical concept is generally traced to Joseph Frank's seminal essay of 1945, "Spatial Form in Modern Literature."1 Frank's basic argument is that modernist literary works are "spatial" insofar as they replace history and narrative sequence with a sense of mythic simultaneity and disrupt the normal continuities of English prose with disjunctive syntactic arrangements. This argument (...) has been attacked on several fronts. An almost universal objection is that spatial form is a "mere metaphor" which has been given misplaced concreteness and that it denies the essentially temporal nature of literature. Some critics will concede that the metaphor contains a half-truth, but one which is likely to distract attention from more important features of the reading experience. The most polemical attacks have come from those who regard spatial form as an actual, but highly regrettable, characteristic of modern literature and who have linked it with antihistorical and even fascist ideologies.2 Advocates of Frank's position, on the other hand, have generally been content to extrapolate his premises rather than criticize them, and have compiled an ever-mounting list of modernist texts which can be seen, in some sense, as "antitemporal." The whole debate can best be advanced, in my view, not by some patchwork compromise among the conflicting claims but by a radical, even outrageous statement of the basic hypothesis in its most general form. I propose, therefore, that far from being a unique phenomenon of some modern literature, and far from being restricted to the features which Frank identifies in those works , spatial form is a crucial aspect of the experience and interpretation of literature in all ages and cultures. The burden of proof, in other words, is not on Frank to show that some works have spatial form but on his critics to provide an example of any work that does not. · 1. Frank's essay first appeared in Sewanee Review 53 and was revised in his The Widening Gyre . Frank's basic argument has not changed essentially even in his most avante-garde statements; he still regards spatial form "as a particular phenomenon of modern avante-garde writing." See "Spatial Form: An Answer to Critics," Critical Inquiry 4 : 231-52. A useful bibliography, "Space and Spatial Form in Narrative," is being complied by Jeffrey Smitten .· 2. This charge generally links the notion of spatial form with Wyndham Lewis and Ezra Pound, the imagist movement, the "irrationality" and pessimistic antihistoricism of modernism, and the conservative Romantic tradition. Frank discusses the complex motives behind these associations in the work of Robert Weimann and Frank Kermode in his "Answer to Critics," pp. 238-48. W. J. T. Mitchell, editor of Critical Inquiry, is the author of Blake's Composite Art, and The Last Dinosaur Book: The Life and Times of a Cultural Icon. The present essay is part of Iconology: The Image in Literature and the Visual Arts. "Diagrammatology" appeared in the Spring 1981 issue of Critical Inquiry. Leon Surette responds to the current essay in "‘Rational Form in Literature’". (shrink)

A brief review is given of the continuous spontaneous localization (CSL) model, in which a classical field interacts with quantized particles to cause dynamical wavefunction collapse. One of the model's predictions is that particles “spontaneously” gain energy at a slow rate. When applied to the excitation of a nucleon in a Ge nucleus, it is shown how a limit on the relative collapse rates of neutron and proton can be obtained, and a rough estimate is made from data. When applied (...) to the spontaneous excitation of 1s electrons in Ge, by a more detailed analysis of more accurate data than given previously, an updated limit is obtained on the relative collapse rates of the electron and proton, suggesting that the coupling of the field to electrons and nucleons is mass proportional. (shrink)

An attempt to discover what can be learned from the recent work of Frank Tipler on the Omega Point theory requires an analysis of his framework of understanding from scientific, philosophical, and theological perspectives. A critique of his crucial ideas, and of the salient points raised by some of his critics, can then be undertaken within the compass of his strengths. A critique of the critiques of Tipler's work allows one to evaluate the extent and limitations of his contributions.

A geometric model is proposed in which the interaction types, namely the strong, weak, electromagnetic, and gravitational interactions, are stratified in a five-dimensional manifold. The strong and electromagnetic interactions are confined to disjoint four-spaces and the weak and gravitational interactions are proposed unified in a five-manifold bounded topologically by the strong and electromagnetic four-spaces. Further, some advantages of the five-dimensional approach to current-current interactions are discussed, and a five-dimensional approach to PCAC is presented. The model is presented in hopes of (...) reconciling some contradictory lines of theoretical thought, and new fields for investigation are stressed. (shrink)

The English critic Bentley first proposed emending the transmitted text of Troades 1109 from teget, the reading of all manuscripts, to leget. Bentley's suggestion subsequently gained wide acceptance and was printed in many later editions of the tragedies, including those of Leo , Richter , and Moricca . More recent critics have favoured retention of the manuscript reading. Carlsson, for example, underlines the distinctive alliterative quality which the reading teget imparts to the line; and the latest commentator on the Troades (...) has produced a spirited defence of the transmitted text: Andromache has not yet realized the condition of the corpse, and is thinking, not of gathering up fragmented limbs, but merely of the formal requirements of burial. What Carlsson defends on grounds of alliteration should be retained on grounds of sense: teget tumuloque tradet is a doublet of which the second part makes clear the religious meaning of the first, more general, word. (shrink)

Based on concepts of self-organization, we interpret apparent motion as the result of a so-called non-equilibrium phase transition of the perceptual system with the stimulus-onset asynchrony (SOA) acting as a control parameter. Accordingly, we predict a significantly increasing variance of the quality index of apparent motion close to critical SOAs. [Shepard].

Rolls demonstrates how reward/punishment systems are key mediators of cognitive appraisal, and this suggests a fundamental, causal role for emotion in thought and behaviour. However, this causal role for emotion seems to drop out of Rolls's model of consciousness, to be replaced by the old idea that emotion is essentially epiphenomenal. We suggest a modification to Rolls's model in which cognition and emotion activate each other reciprocally, both in appraisal and consciousness, thus allowing emotion to maintain its causal status where (...) it matters most. (shrink)

Recent studies uncovered critical roles of the adhesion protein E‐cadherin in health and disease. Global inactivation of Cdh1, the gene encoding E‐cadherin in mice, results in early embryonic lethality due to an inability to form the trophectodermal epithelium. To unravel E‐cadherin's functions beyond development, numerous mouse lines with tissue‐specific disruption of Cdh1 have been generated. The consequences of E‐cadherin loss showed great variability depending on the tissue in question, ranging from nearly undetectable changes to a complete loss of tissue structure (...) and function. This review focuses on these studies and discusses how they provided important insights into E‐cadherin's role in cell adhesion, proliferation and differentiation, and its consequences for biological processes as epithelial‐to‐mesenchymal transition, vascularization, and carcinogenesis. Lastly, we present some perspectives and possible approaches for future research. (shrink)

A critical discussion is provided of three central assumptions underlying Nunez's approach to modeling cortical activity. A plea is made for neurophysiologically realistic models involving nonlinearities, multiple time scales, and stochasticity.

This chapter describes the potential far‐reaching consequences of contemplative higher education for the fields of science and medicine.

We give a historical overview of the development of almost 50 years of empirical research on the affordances in the past and in the present. Defined by James Jerome Gibson in the early development of the Ecological Approach to Perception and Action as the prime of perception and action, affordances have become a rich topic of investigation in the fields of human movement science and experimental psychology. The methodological origins of the empirical research performed on affordances can be traced back (...) to the mid 1980’s and the works of Warren (1984, 1988) and Michaels (1988). Most of the research in Ecological Psychology performed since has focused on the actualization of discretely defined actions, the perception of action boundaries, the calculation of pi-numbers, and the measurement of response times. The research efforts have resulted in advancements in the understanding of the dynamic nature of affordances, affordances in a social context and the importance of calibration for perception of affordances. Although affordances are seen as an instrumental part of the control of action most studies investigating affordances do not pay attention to the control of the action. We conclude that affordances are still primarily treated as a utility to select behaviour, which creates a conceptual barrier that hinders deeper understanding of affordances. A focus on action-boundaries has largely prevented advancement in other aspects of affordances, most notably an integrative understanding of the role of affordances in the control of action. (shrink)

The topic of homonymy, especially the variety of homonymy that has gone under the title, “focal meaning,” is of fundamental importance to large portions of Aristotle’s work—not to mention its central place in the ongoing controversies between Aristotle and Plato. It is quite astonishing, therefore, that the topic should have gone so long without a book-length treatment. And it is all the more gratifying that the new book on homonymy by Christopher Shields should be so comprehensive, and of such uniformly (...) high quality. Everyone who cares about Aristotle will be in his debt. (shrink)

This book takes up the central themes of Aristotle's metaphysical theory and the various transformations they undergo prior to their full expression in the Metaphysics. Aristotle's metaphysics is bedevilled by classic puzzles involving such notions as form, predication, universal, and substance, which result from his attempt to adapt the various requirements on primary substance developed in his earlier works so that they fit the very different metaphysical picture in his later work. Professor Lewis argues that Aristotle is himself aware (...) of most if not all of these difficulties and in the Metaphysics works hard to ensure the coherence of his theory. He presents Aristotle's views as a formal theory complete with axioms, definitions, and theorems. (shrink)

Frank A. Lewis presents a close study of book Zeta of Aristotle's Metaphysics, one of his most dense and controversial texts, commonly understood to contain his deepest thoughts on the definition of substance and related metaphysical issues. Lewis argues that Aristotle returns to the causal view of primary substance from his Posterior Analytics.