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)

If dominating functions in ω ω are adjoined repeatedly over a model of GCH via a finite-support c.c.c. iteration, then in the resulting generic extension there are no long towers, every well-ordered unbounded family of increasing functions is a scale, and the splitting number s (and hence the distributivity number h) remains at ω 1.

Should mental health insurance cover only disorders found in DSM‐IV, or should it be extended to treatment for ordinary shyness, unhappiness, and other responses to life's hard knocks?

The paper considers the recently published British Medical Association Guidance on ethical issues arising in relation to rationing of treatment during the COVID-19 Pandemic. It considers whether it...

In his new book, Constitutional Essentials, Frank Michelman provides a splendid elaboration and defense of ‘the constitutional theory of political liberalism’ implicit in John Rawls’s classic work, Political Liberalism. In this essay, we make some observations about what a difference 30 years makes, comparing the political and constitutional climate in which Rawls wrote and published Political Liberalism in 1993 with the climate in which Michelman wrote and published this exegesis of it. We focus on (1) changes in our circumstances of (...) pluralism, including the accentuation of polarization and unreasonable views, and (2) the simultaneous breakdown of trust in the Supreme Court authoritatively to resolve disputes concerning constitutional essentials. Throughout, we acknowledge and seek to reckon with the possibility that Michelman may have given Rawls’s liberal principle of legitimacy its fullest, most coherent account just at the moment when the possibility of realizing it seems to be passing. (shrink)

Unchanging God -- Simple God -- Simple God lost -- Eternal creator -- One God, three persons.

This paper discusses global corporate citizenship in the twenty-first century. The primary focus is on the responsibility of managementeducators to foster among students an understanding of the causes and consequences of business activitiy that creates organizationalwealth, including the role of stakeholders. The modern corporation is a stakeholder enterprise: stakeholders enable the business to create wealth and require that it distribute wealth appropriately. The stakeholder enterprise model, which has been so economically successful, also implies corporate citizenship responsibilities. The Clarkson Principles are (...) discussed as a means through which educators and managers can better understand and address the challenges of corporate citizenship in the modern world. (shrink)

A series of topical philosophy studies aiming to publish original essays by foremost thinkers in their fields, with each volume confined to a main area of philosophical research.

An adequate approach to any of Aristotle's qualitative parts of tragedy must be grounded in an understanding of their hierarchical ranking within the Poetics. Any "whole" must present "a certain order in its arrangement of parts" ,1 and in a drama each part is "for the sake of" the one "above" it. Contrary to Rosenstein's formulation, for instance, the Aristotelian view is that character as a form "concretizes" and individualizes thought as matter. Rosenstein's question as to whether "these . . (...) . indeed form a genuine disjunction" should not even arise. By ignoring the hierarchy, and therefore collapsing it, Rosenstein weakens his otherwise sound assertion that tragedy is not philosophy. Such is the result, whether intended or not, of holding that "thought must also be some form or concretization of action, just as plot and character are" . This vocabulary seems to suggest in the end that a tragic work is organized by philosophical "themes." "To understand spoken thought as an object of imitation in this manner is to understand it not merely as a content or object being imitated . . . but as the supposedly valid expression of an interpretation of the doings of the aesthetically worked world generally. . . . Thought in this sense becomes theme" . · 1. Unless otherwise noted, all quotations of Aristotle are from The Basic Works of Aristotle, ed. Richard McKeon . James E. Ford responds in this essay to Leon Rosenstein's "On Aristotle and Thought in the Drama" . An assistant professor of English at Brigham Young University—Hawaii Campus, he is currently writing on interpretative theory. See also: "Metaphor and Transcendence" by Karsten Harries in Vol. 5, No. 1. (shrink)

This commentary raises a number of questions in connection with Colin Koopman's paper “Conceptual Analysis for Genealogical Philosophy: How to Study the History of Practices after Foucault and Wittgenstein.” Specifically, this commentary asks about the precise relationship between concepts and practices in Koopman's account and the possibility of resisting certain practices of subjectivation.

Systems theory provides a surprisingly fruitful approach to several important ideas held in common by Paul Tillich and Pierre Teilhard de Chardin. These include complexity or organization as the key to understanding the distinction between the inorganic and the organic, and hierarchy or levels in complex systems. Teilhard and systems theorists accept hierarchy as fundamental. Tillich questions the concept and prefers “dimensions,” including the inorganic, organic, psychological, spiritual, and historical dimensions. Tillich's rejection of hierarchy is questioned, but significant correlations are (...) discovered in the systems interpretation of the psychological and spiritual dimensions as well as in the use of “centeredness” by both thinkers. (shrink)

Institutional investors are increasingly becoming active owners through voting their shares and engaging in dialogue with investee companies to improve corporate environmental, social and corporate governance (ESG) performance. This article applies a model of stakeholder salience to the shareholder context, analysing the attributes of power, legitimacy and urgency, to determine the factors that are likely to enhance shareholder salience. It is found that a strong business case and the values of the managers of investee companies are likely to be the (...) most important contributors to shareholder salience. (shrink)

Let κ denote a regular uncountable cardinal and NS the normal ideal of nonstationary subsets of κ. Our results concern the well-known open question whether NS fails to be κ + -saturated, i.e., are there κ + stationary subsets of κ with pairwise intersections nonstationary? Our first observation is: Theorem. NS is κ + -saturated iff for every normal ideal J on κ there is a stationary set $A \subseteq \kappa$ such that $J = NS \mid A = \{X \subseteq (...) \kappa:X \cap A \in NS\}$ . Turning our attention to large cardinals, we extend the usual (weak) Mahlo hierarchy to define "greatly Mahlo" cardinals and obtain the following: Theorem. If κ is greatly Mahlo then NS is not κ + -saturated. Theorem. If κ is ordinal Π 1 1 -indescribable (e.g., weakly compact), ethereal (e.g., subtle), or carries a κ-saturated ideal, then κ is greatly Mahlo. Moreover, there is a stationary set of greatly Mahlo cardinals below any ordinal Π 1 1 -indescribable cardinal. These methods apply to other normal ideals as well; e.g., the subtle ideal on an ineffable cardinal κ is not κ + -saturated. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:166 HUME'S INTEREST IN NEWTON AND SCIENCE Many writers have been forced to examine — in their treatments of Hume's knowledge of and acquaintance with scientific theories of his day — the related questions of Hume's knowledge of and acquaintance with Isaac Newton and of the nature and extent of Newtonian influences upon Hume's thinking. Most have concluded that — in some sense — Hume was acquainted with and (...) influenced by Newton's thought in particular and scientific thought in general. The genesis of this paper is the recent point of view put forward by Peter Jones which challenges the many permutations of this almost ritualistic standard line by removing Hume entirely from the Newtonian and the scientific scenes of thought. Jones argues that Hume knew less about Newton and science, and needed to know less about Newton and 2 science, than he believes is required by the above interpretation. Indeed, Jones argues that Hume's fundamental assumptions, which, according to Jones, derive ultimately from a form of Ciceronian humanism, drive a "wedge" between Newton's thought and that of 3 Hume. Even Hume's introductory remarks in the Treatise about his universal "science of man" are, for Jones, a declaration of independence from the materialistic trend (as Jones sees it) of Newtonian 4 science and not, as so many commentators have maintained — however tenuously or strongly evidence for linkage of Hume's project with Newtonian or scientific thought. Jones baldly argues that Hume totally lacked interest in science in general and in Newton and Newtonian science in particular. Following J. H. Burton's observation that Hume's work is surprisingly free from the "opinions" of contemporary scientists, 167 Jones states there is no evidence that Hume ever studied science at the University of Edinburgh or that he "pursued" scientific studies of any formal sort. Regarding Newtonian scientific thought, he emphasizes the paucity of specifically Newtonian scientific textbooks in the early eighteenth century 7 which might have been available for Hume to study and argues that nowhere in Hume's writings is there evidence of precise and detailed knowledge of Newton's science beyond what is available in Q Chamber's Cyclopaedia. Jones acknowledges that, in the Introduction to the Treatise, Hume utilizes a "general version" of Newton's "Regulae Philosophandi" from the beginning of Book III of Newton's Principia. Nevertheless, in Jones' view, Hume's fundamentally humanistic orientation separates him completely from g any Newtonian influence. Finally, according to Jones, Hume does not betray the least bit of knowledge of Newton's mathematics and its role in Newton's experimental methodology. On this evidence Jones grounds his central claim of Hume's "total lack of interest in contemporary science." What references there are to Newton and to science in Hume's works Jones finds "traceable to essentially literary predecessors such as Fontenelle or Montesquieu, or to standard works of theologians ] 2 or free-thinkers." The absence of clearly direct references to what Jones feels are scientific works results both from Hume's "total lack of interest in science" and from his commitment to a form of Ciceronian humanism which is "inimical" to what Jones finds to be the obvious materialistic tendencies of 13 science in the early modern period. Jones' account of the Ciceronian and French contexts of Hume's thought is excellent. But his claim that Hume had no interest whatsoever in science 168 is simply too strong and finally forces us to view science in Hume's day as equivalent to science in our own time, a manifestly anachronistic point of view. Throughout this paper, my argument will be conditioned by my view that Hume's interest in science cannot be separated from his epistemology or his religious scepticism. Hume's interest in science was precisely that of a man of letters of the eighteenth century vitally engaged in determining the proper use of scientific methodology in establishing the limits of the secular science of man once it has 14 been freed from the fetters of theology. Hume's interest in theological and epistemological issues inevitably gave rise to a strong interest on his part in the science of his day and in Newton's contributions... (shrink)

The main thesis of this paper is that it is not possible to determine the nature of epistemic justification apart from scientific psychological investigation. I call this view the strong thesis of methodological psychologism. Two sub-theses provide the primary support for this claim. The first sub-thesis is that no account of epistemic justification is correct which requires for the possession of at least one justified belief a psychological capacity which humans do not have. That is, the correct account of epistemic (...) justification must be psychologically realistic. The second sub-thesis is that it is not possible to determine whether an account of epistemic justification is psychologically realistic apart from scientific psychological investigation. After defending these subtheses, I point out some interesting consequences of the overall thesis which present a challenge to traditional epistemology. (shrink)

A philosophical movement, correctly called logical pragmatism, is growing up around the philosophy of W. V. O. Quine. Soviet scholars follow this development with clear and well-grounded understanding of the origins and tenets of the system. This essay continues the "dialogue" between contemporary Marxism-Leninism and logical pragmatism recommended by Soviet scholars.

It is shown that if ZF is consistent, then so is ZFC + GCH + "There is a graph with cardinality ℵ 2 and chromatic number ℵ 2 such that every subgraph of cardinality ≤ ℵ 1 has chromatic number ≤ ℵ 0 ". This partially answers a question of Erdos and Hajnal.

What are cells? How are they related to each other and to the organism as a whole? These questions have exercised biology since Schleiden and Schwann (1838–1839) first proposed cells as the key units of structure and function of all living things. But how do we try to understand them? Through new technologies like the achromatic microscope and the electron microscope. But just as importantly, through the metaphors our culture has made available to biologists in different periods and places. These (...) two new volumes provide interesting history and philosophy of the development of cell biology. Reynolds surveys the field's changing conceptual structure by examining the varied panoply of changing metaphors used to conceptualize and explain cells – from cells as empty boxes, as building blocks, to individual organisms, to chemical factories, and through many succeeding metaphors up to one with great currency today: cells as social creatures in communication with others in their community. There is some of this approach in theVisionsedited collection as well. But this collection also includes rich material on the technologies used to visualize cells and their dialectical relationship with the epistemology of the emerging distinct discipline of cell biology. This volume centres on, but is not limited to, ‘reflections inspired by [E.V.] Cowdry's [1924 volume]General Cytology’; it benefits from a conference on the Cowdry volume as well as a 2011 Marine Biological Lab/Arizona State University workshop on the history of cell biology. (shrink)

Role of lawyer -- Regulation of lawyers -- Defining and forming the lawyer-client relationship -- Compensating lawyers -- Confidentiality -- Incompatible relations -- Representing organizations -- Duties to the court and others -- Advertising and solicitation -- Judicial conduct.

Introduction -- Interlude #1: Consider the oxen -- The agrarian ideals of Cerridwen farm -- Vine sanctuary responds -- Interlude #2: Moral syllogism 101 -- Green Mountain College students mount a defense -- Professors and administrators make their case -- Voices of dissent shatter the cocoon at GMC -- Interlude #3: President Fonteyn provides a reprieve -- A wise intervention, a suspicious death -- Conclusion -- About the author -- About the publisher.

The essays are happily reprinted here in a systematic manner. The first eight, written with a minimal use of technical logic, develop Prior's views about three main philosophical problems of time: temporal succession, time and determinism, and existence and temporal identity. There follow five papers of considerably more formal character, in which Prior at once expands and renders more precise his philosophical views. The ultimate aim of the present study is to clarify certain points connected with the above problems about (...) time. But the immediate task is to provide a comprehensive discussion of some of Prior's most important methodological and doctrinal positions concerning these problems. (shrink)

Fully grown Xenopus oocytes can remain in their immature state essentially indefinitely, or, in response to the steroid hormone progesterone, can be induced to develop into fertilizable eggs. This process is termed oocyte maturation. Oocyte maturation is initiated by a novel plasma membrane steroid hormone receptor. Progesterone brings about inhibition of adenylate cyclase and activation of the Mos/MEK1/p42 MAP kinase cascade, which ultimately brings about the activation of the universal M phase trigger Cdc2/cyclin B. Oocyte maturation provides an interesting example (...) of how signaling cascades entrain the cell cycle clock to environmental changes. BioEssays 21:833–842, 1999. © 1999 John Wiley & Sons, Inc. (shrink)