Progressive supranuclear palsy is a movement disorder with prominent tau neuropathology. Brain diseases with abnormal tau deposits are called tauopathies, the most common of which is Alzheimer's disease. Environmental causes of tauopathies include repetitive head trauma associated with some sports. To identify common genetic variation contributing to risk for tauopathies, we carried out a genome-wide association study of 1,114 individuals with PSP and 3,247 controls followed by a second stage in which we genotyped 1,051 cases and 3,560 controls for the (...) stage 1 SNPs that yielded P ≤ 10-3. We found significant previously unidentified signals associated with PSP risk at STX6, EIF2AK3 and MOBP. We confirmed two independent variants in MAPT affecting risk for PSP, one of which influences MAPT brain expression. The genes implicated encode proteins for vesicle-membrane fusion at the Golgi-endosomal interface, for the endoplasmic reticulum unfolded protein response and for a myelin structural component. © 2011 Nature America, Inc. All rights reserved. (shrink)

In the leadership literature of the past 100 years or so, rhetoric has been a topic for a long time and ethics was introduced some 30 years ago. However, the three topics, leadership, rhetoric, and ethics, have not been connected. This is astonishing because when ethical leadership made its comeback, scholars acknowledged the debt that ethical leadership owes to Aristotelian ideas. For Aristotle, leadership, ethics, and rhetoric were inseparable: without ethics, there could neither be good leadership nor rhetoric, and rhetoric (...) was the bridge from leader to follower and back. Aristotle is known as the practical philosopher and we argue that closing this major lacuna in leadership theory, would be beneficial for practice too and would help prevent Theranos-like scandals. The lacuna lies in what some call a Machiavellian view of leadership and rhetoric: both are regarded as amoral tools to achieve given ends. Aristotle would bristle at that idea. Both, leadership and rhetoric, to be good, must aim at the noble. The noble is not dictated by a heroic despot nor by a selfless saint but is understood by a leader because s/he is a socially embedded individual. We argue that leadership should be understood as personal development, that organisational rules must not inhibit virtue, that leadership is more about listening than talking, that synthesising that which is heard is central, and finally, that the common, not the collective, good is the goal of leadership. (shrink)

Introduction Families of patients with dementia may need support in difficult end-of-life decision making. Such guidance may be culturally sensitive. Methods To support families in Canada, a booklet was developed to aid decision making on palliative care issues. For reasons of cost effectiveness and promising effects, we prepared for its implementation in Italy, the Netherlands and Japan. Local teams translated and adapted the booklet to local ethical, legal and medical standards where needed, retaining guidance on palliative care. Using qualitative content (...) analyses, we grouped and compared adaptations to understand culturally sensitive aspects. Results Three themes emerged: (1) relationships among patient, physician and other professionals—the authority of the physician was more explicit in adapted versions; (2) patient rights and family position—adding detail about local regulations; and (3) typology of treatments and decisions. Considerations underlying palliative care decisions were detailed (Dutch and Italian versions), and the Japanese version frequently referred to professional and legal standards, and life-prolongation was a competing goal. Text on artificial feeding or fluids and euthanasia was revised extensively. Conclusions Providing artificial feeding and fluids and discussing euthanasia may be particularly sensitive topics, and guidance on these subjects needs careful consideration of ethical aspects and possible adaptations to local standards and practice. The findings may promote cross-national debate on sensitive, core issues regarding end-of-life care in dementia. (shrink)

There is increasing evidence that dynamic changes to chromatin, chromosomes and nuclear architecture are regulated by RNA signalling. Although the precise molecular mechanisms are not well understood, they appear to involve the differential recruitment of a hierarchy of generic chromatin modifying complexes and DNA methyltransferases to specific loci by RNAs during differentiation and development. A significant fraction of the genome-wide transcription of non-protein coding RNAs may be involved in this process, comprising a previously hidden layer of intermediary genetic information that (...) underpins developmental ontogeny and the differences between species, ecotypes and individuals. It is also evident that RNA editing is a primary means by which hardwired genetic information in animals can be altered by environmental signals, especially in the brain, indicating a dynamic RNA-mediated interplay between the transcriptome, the environment and the epigenome. Moreover, RNA-directed regulatory processes may also transfer epigenetic information not only within cells but also between cells and organ systems, as well as across generations. (shrink)

An ideal vision model accounts for behavior and neurophysiology in both naturalistic conditions and designed lab experiments. Unlike psychological theories, artificial neural networks (ANNs) actually perform visual tasks and generate testable predictions for arbitrary inputs. These advantages enable ANNs to engage the entire spectrum of the evidence. Failures of particular models drive progress in a vibrant ANN research program of human vision.

Marcel is concerned with human existence or, better, with the quality of human life which we usually recognize more or less clearly under the concepts of freedom and responsibility. Such humanity is a de jure rather than a strictly de facto notion. We are always in danger of losing, caricaturing, or forfeiting our humanity and thus the adjective subhuman assumes a genuine significance, at least as indicating a limiting concept that stands as a warning before those "techniques of degradation," (...) the modern systems of mass propaganda and thought control. (shrink)

Because of their basic level, textbooks show the assumptions and biases of art historians more clearly than does advanced, and therefore more restricted, scholarship. Textbooks are the rock, as it were, within which lie the strata of historical method. They bury, and so preserve for the good and ill of students , not so much individual historical data, which can be picked up or rejected rather easily, as those things which give the appearance of intellectual grasp to historical writing: its (...) generalizations, its interpretations, its sweeping perspectives. The successive editions of Helen Gardner's Art through the Ages can tell us much about the assumptions that have pervaded art historical education in America over the past century. The first edition, published fifty years ago last year, is worth looking at in some detail, because for all its seminal importance in the teaching of art history it is by now little more than a deposit in library stacks. A mere glance will show that it is not ours. Indeed, the distance we have gone since then is exactly measured by the gaucheries it displays. It is half the length of modern surveys, and it makes no pretense either to completeness or to objectivity. It is arranged by period and style until we reach the Renaissance , at which point, in keeping with the interest of an earlier age in national characteristics, each country receives its due chapter. The Italian Renaissance, as befits the central position of the primitives in American taste then, has four chapters to itself. Thereafter, except for a final, brief section on contemporary art, each national school is taken to the period of its decline. This, of course, will vary. France is taken through Cézanne; England through the Pre-Raphaelites and William Morris; Spain, thanks to Goya, into the early nineteenth century; and Dutch and Flemish art only through the seventeenth century, but without Bosch or Bruegel. As for Germany, though the chapter heading promises us "From the Gothic Age to the Nineteenth Century," in fact it is on Durer and Holbein. What fulfills the promise of the title appears in its entirety thus: "After the death of these two masters, largely on account of exhaustion from wars there was very little production, until the second great manifestation of the German people came in the music of the eighteenth and nineteenth centuries."1 No pretense here at dutiful compilation; high points, after all, are high points. · 1. Helen Gardner, Art through the Ages: An Introduction to Its History and Significance , p. 345. Marcel Franciscono is the author of Walter Gropius and the Creation of the Bauhaus in Weimar. He is associate professor of art history at the University of Illinois at Urbana-Champaign. (shrink)

The aim of the paper is to show the philosophy of G. Marcel as a personally expe_rienced encounter with the most burning problems of our times. In his view the philosophical reflection is discovering of the meaningful order of the world. Attention is paid also to the influence, of G. Marcel's work on the thinking of Slovak and Czech philosophers.

Immanuel Kant states that indirect arguments are not suitable for the purposes of transcendental philosophy. If he is correct, this affects contemporary versions of transcendental arguments which are often used as an indirect refutation of scepticism. I discuss two reasons for Kant’s rejection of indirect arguments. Firstly, Kant argues that we are prone to misapply the law of excluded middle in philosophical contexts. Secondly, Kant points out that indirect arguments lack some explanatory power. They can show that something is true (...) but they do not provide insight into why something is true. Using mathematical proofs as examples, I show that this is because indirect arguments are non-constructive. From a Kantian point of view, transcendental arguments need to be constructive in some way. In the last part of the paper, I briefly examine a comment made by P. F. Strawson. In my view, this comment also points toward a connection between transcendental and constructive reasoning. (shrink)

In 2004 a survey was conducted in the member states of the European Union designed to gain greater insight into the views on control strategies for foot and mouth disease, classical swine fever, and avian influenza with respect to the epidemiological, economic and social-ethical consequences of each of these animal diseases. This article presents the results of the social-ethical survey. A selection of stakeholders from each member state was asked to prioritize issues for the prevention and control of these diseases. (...) A majority of stakeholders chose preventive measures as the preferred issue. An analysis was done to determine whether there were differences in views expressed by stakeholders from member states with a history of recent epidemics and ones without such a history, and whether there were regional differences. There were no differences between member states with or without a history of recent epidemics. There were indeed regional differences between the priority orders from Northern and Southern Europe on the one hand, and from Eastern Europe on the other. (shrink)

Eric Weil, who died at Nice on February 1, 1977, was a prominent philosopher and an authority on Hegel. He was born at Parchim on June 6, 1904. From 1922 to 1928 he studied under E. Cassirer at Hamburg and Berlin. His doctoral thesis “Die Philosophie des Pietro Pomponazziz” was published in 1932 in the Archiv für Geschichte der Philosophie. In 1933 he migrated to France, received French nationality, took part in World War II, and became a prisoner of war (...) in Germany. From 1946 to 1956 he taught in the Ecole Practique des Hautes Etudes in Paris, graduated again, this time in France, with La Logique de la philosophie, his main work published in 1950, was a professor at the universities of Lille, where he organized the Congress of the Internationale Hegel Vereinigung in 1968, and Nice, received an honorary degree at Munster in 1969. His main works are also: Hegel et l’Etat, Philosophie politique, Philosophie morale, Problemes kantiens, Essais et Conférences. For a complete bibliography up to 1970 see Archives de Philosophie 1970, p. 605–622. He helped to get rid of some false interpretations rejected also emphatically the marxist interpretation of Hegel. For Weil, as for, so he thought, Aristotle and Hegel, philosophy is an endless endeavor to build up a “discours coherent” of reality as a whole. Man is a finite being, needy, compelled to act in order to live but, as he is at the same time reasonable, he may live meaningfully, promote freedom and justice, undertake to understand himself and the whole of reality, even violence and error, and mainly the behavior of other people and their conceptions of the world. As philosophy considers man not as an object but as a subject, it is not a science properly but, mainly as the logic of philosophy, it is as coherent and as strict as a science. Weil disliked “constructivism” - as deducing a system from a “necessary being”, or predicting the course of history. Though he was often a fellow traveller of Hegel, he acknowledged more and more that he felt a kantian, but a “post-hegelian” kantian. (shrink)

L’auteure, Simone Goyard-Fabre, est professeure émérite de philosophie à l’Université de Caen, en plus d’assumer la codirection scientifique du Thesaurus de philosophie du droit, à l’Université de Paris II. Poursuivant avec cet essai une réflexion, ponctuée de moult publications, sur l’architectonique juridico-politique de la Modernité occidentale et sur ses enjeux théoriques et pratiques, Goyard-Fabre dessine d’abord, avec sa vivacité habituelle, les principaux philosophèmes qui ont présidé à l’édification de ce qu’elle désigne comme la «cathédrale rationnelle du droit politique moderne», qui (...) trouve ses fondations dans les principes de l’ordre public, de l’autorité centralisatrice du Pouvoir et de la constitutionnalité. (shrink)

Cette étude a eu pour objet le journal d'un curé de campagne, mais un journal qui n'a pas été écrit à la manière de Bernanos. Il s'agit en effet, comme l'indique le titre, d'un bulletin paroissial, qui a aussi fait office, à l'occasion, de bulletin communal. Dans la préface et l'introduction (p. 3-6), M. Winninger présente le curé Ackerer, auquel il était lié d'amitié depuis le temps de leurs études communes, et explique l'intérêt de cette imposante masse documentaire constituée au (...) fil d'une .. (shrink)