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 heroic Latin hexameter, after the essential alternation of long and short syllables, by far the most important feature is unquestionably the caesura. Nevertheless, ancient writers on metre dismiss it with the most cursory notice; all we get from them is that the chief caesura is the penthemimeral, the trochaic and hephthemimeral coming next; the fourth trochaic and the bucolic are usually rejected, and the trihemimeral is mentioned only by Ausonius, Modern writers, among whom are Müller and Winbolt, deal (...) with the question at greater length, but do not agree even on fundamental points, and often base their statements on an insufficient analysis of the extant remains of Latin hexameter verse. The purpose of the following paper is to attempt a more complete analysis, at least in the case of Virgil, the acknowledged master of the Latin hexameter. But before we proceed further there are two preliminaries which must be settled—what are the main types of caesura, and how many caesurae are admissible in one verse? (shrink)

Nature of the problem: Testimony from scientists. Reflex action and theism (1881) by W. James. The organization of thought (1916) by A.N. Whitehead. The changing scientific scene 1900-1950 (1952) by J.B. Conant. A note on methods of analysis (1943) by H.J. Muller. The way things are (1959) by P.W. Bridgman. A definition of style (1948) by J.R. Oppenheimer.--Consequences of the problem: Testimony from artists and writers. Existentialism (1947) by J.-P. Sartre. The testimony of modern art (1957) by W. Barrett. (...) Parts of speech and punctuation (1935) by G. Stein. The waves (1931) by V. Woolf. The imperfect paradise, by W. Stevens. A note on style and the limits of language, by W. Gibson. (shrink)

May lethal autonomous weapons systems—‘killer robots ’—be used in war? The majority of writers argue against their use, and those who have argued in favour have done so on a consequentialist basis. We defend the moral permissibility of killer robots, but on the basis of the non-aggregative structure of right assumed by Just War theory. This is necessary because the most important argument against killer robots, the responsibility trilemma proposed by Rob Sparrow, makes the same assumptions. We show that the (...) crucial moral question is not one of responsibility. Rather, it is whether the technology can satisfy the requirements of fairness in the re-distribution of risk. Not only is this possible in principle, but some killer robots will actually satisfy these requirements. An implication of our argument is that there is a public responsibility to regulate killer robots ’ design and manufacture. (shrink)

This volume is a critical edition of the eight-year correspondence between Gottfried Wilhelm Leibniz and Burcher de Volder, professor of philosophy and mathematics at Leiden University. Containing the surviving correspondence between Leibniz and De Volder, the volume also presents a generous selection from the letters between Leibniz and his friend Johann Bernoulli, through whose intercession the correspondence began. Bernoulli acted as intermediary throughout, and the often candid discussions between Leibniz and Bernoulli provide illuminating background to the correspondence proper. Each of (...) the selections appears both in the original Latin and in English translation. (shrink)

The issue of advocacy has dominated discussion of the ethical dilemmas facing nurses. However, despite this, nurses seem to be no further towards a solution of how they can be effective advocates for patients without compromising their working identity or facing conflicts of loyalty. This article considers some of the problems around advocacy and, by the use of critical incidents written by nurses involved in a diploma module, attempts to highlight where the problem could lie. A communications model is outlined, (...) using a theoretical framework taken from the work of Jürgen Habermas, and applied to nursing practice. Finally, two examples are given from the research, which illustrate how the model could be used, highlighting the problems and pitfalls that still have to be overcome. The conclusion is a positive one, in that it suggests that advocacy is possible if nurses re-examine their practice in the light of the model proposed.Copyright of Nursing Ethics is the property of Sage Publications Inc. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (shrink)

Saul Kripke is one of the most original and creative philosophers writing today. His work has had a tremendous impact on the direction that philosophy has taken in the last thirty years and continues to dominate some of its most fundamental aspects. Given Kripke's importance it is perhaps surprising that there is no introduction to his philosophy available to the general student. This book fills that gap. As much of Kripke's work is highly technical, the book's central aim is to (...) provide clear exposition of Kripke's ideas in a form that is understandable to a beginning readership as well as a commentary on them that more advanced students will find useful. The book begins with a discussion of Kripke's early work on modal logic, which provides the foundation for many of his later philosophical contributions, before examining in detail Kripke's central ideas and arguments contained in Naming and Necessity. In further chapters, Kripke's work on semantic paradoxes and his theory of truth are outlined as well as his controversial interpretation of Wittgenstein's famous private language argument. Kripke's ideas are situated alongside those of his precursors and some of the most important and interesting responses to them are explored. The reader is thus able to appreciate the path-breaking nature of Kripke's contributions, how they have challenged fundamentally traditional interpretations, and how they have sparked some of the most important philosophical debates of recent years. (shrink)

Saul Kripke is one of the most original and creative philosophers writing today. His work has had a tremendous impact on the direction that philosophy has taken in the last thirty years and continues to dominate some of its most fundamental aspects. Given Kripke's importance it is perhaps surprising that there is no introduction to his philosophy available to the general student. This book fills that gap. As much of Kripke's work is highly technical, the book's central aim is to (...) provide clear exposition of Kripke's ideas in a form that is understandable to a beginning readership as well as a commentary on them that more advanced students will find useful. The book begins with a discussion of Kripke's early work on modal logic, which provides the foundation for many of his later philosophical contributions, before examining in detail Kripke's central ideas and arguments contained in Naming and Necessity. In further chapters, Kripke's work on semantic paradoxes and his theory of truth are outlined as well as his controversial interpretation of Wittgenstein's famous private language argument. Kripke's ideas are situated alongside those of his precursors and some of the most important and interesting responses to them are explored. The reader is thus able to appreciate the path-breaking nature of Kripke's contributions, how they have challenged fundamentally traditional interpretations, and how they have sparked some of the most important philosophical debates of recent years. (shrink)