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)

This Companion provides a fresh and comprehensive account of this outstanding work, which remains among the most frequently read works of Greek philosophy, indeed of Classical antiquity in general. The sixteen essays, by authors who represent various academic disciplines, bring a spectrum of interpretive approaches to bear in order to aid the understanding of a wide-ranging audience, from first-time readers of the Republic who require guidance, to more experienced readers who wish to explore contemporary currents in the work’s interpretation. The (...) three initial chapters address aspects of the work as a whole. They are followed by essays that match closely the sequence in which topics are presented in the ten books of the Republic. Since the Republic returns frequently to the same topics by different routes, so do the authors of this volume, who provide the readers with divergent yet complementary perspectives by which to appreciate the Republic’s principal concerns. (shrink)

This full-length study of Plato's dialogue Phaedrus, now in paperback, is written in the belief that such concerted scrutiny of a single dialogue is an important part of the project of understanding Plato so far as possible 'from the inside' - of gaining a feel for the man's philosophy. The focus of this account is on how the resources both of persuasive myth and of formal argument, for all that Plato sets them in strong contrast, nevertheless complement and reinforce each (...) other in his philosophy. Not only is the dialogue in its formal structure a dovetail of myth and argument, but the philosophic life that it praises is also shaped by an acknowledgement of the limitations of argument and the importance of mythical understanding. By means of this correlation of form and content Plato invites his readers, through the very act of reading, to take a first step along the path of the philosophical life. (shrink)

Tracing a central theme of Plato's Republic , G. R. F. Ferrari reconsiders in this study the nature and purpose of the comparison between the structure of society and that of the individual soul. In four chapters, Ferrari examines the personalities and social status of the brothers Glaucon and Adeimantus, Plato's notion of justice, coherence in Plato's description of the decline of states, and the tyrant and the philosopher king—a pair who, in their different ways, break with the terms of (...) the city-soul analogy. In addition to acknowledging familiar themes in the interpretation of the Republic —the sincerity of its utopianism, the justice of the philosopher's return to the Cave—Ferrari provocatively engages secondary literature by Leo Strauss, Bernard Williams, and Jonathan Lear. With admirable clarity and insight, Ferrari conveys the relation between the city and the soul and the choice between tyranny and philosophy. City and Soul in Plato's Republic will be of value to students of classics, philosophy, and political theory alike. (shrink)

The ability to feel pain is a property of human beings that seems to be based entirely in our biological natures and to place us squarely within the animal kingdom. Yet the experience of pain is often used as an example of a mental attribute with qualitative properties that defeat attempts to identify mental events with physiological mechanisms. I will argue that neurophysiology and psychology help to explain the interwoven biological and subjective features of pain and recommend a view of (...) pain which differs in important respects from the one most commonly accepted. (shrink)

First published in 2000, this translation of one of the great works of Western political thought is based on the assumption that when Plato chose the dialogue form for his writing, he intended these dialogues to sound like conversations - although conversations of a philosophical sort. In addition to a vivid, dignified and accurate rendition of Plato's text, the student and general reader will find many aids to comprehension in this volume: an introduction that assesses the cultural background to the (...) Republic, its place within political philosophy, and its general argument; succinct notes in the body of the text; an analytical summary of the work's content; a full glossary of proper names; a chronology of important events; and a guide to further reading. The result is an accomplished and accessible edition of this seminal work, suitable for philosophers and classicists as well as historians of political thought at all levels. (shrink)

This paper presents a theoretical elaboration of the ethical framework of classical capitalism as formulated by Adam Smith in reaction to the dominant mercantilism of his day. It is seen that Smith's project was profoundly ethical and designed to emancipate the consumer from a producer and state dominated economy. Over time, however, the various dysfunctions of a capitalist economy — e.g., concentration of wealth, market power — became manifest and the utilitarian ethical basis of the system eroded. Contemporary capitalism, dominated (...) as it is by large corporations, entrenched political interests and persistent social pathologies, bears little resemblance to the system which Smith envisioned would serve the common man. Most critiques of capitalism are launched from a Marxian-based perspective. We find, however, that by illustrating the wide gap between the reality of contemporary capitalism and the model of amoral political economy developed by Smith, the father of capitalism proves to be the most trenchant critic of the current order. (shrink)

Informed consent is required for any medical procedure although the situations in which it is given are beset by uncertainties and indeterminacies. These make medicolegal scrutiny of such situations very difficult. Although some people find the decision in the Sidaway case incomprehensible because of its continuing regard for a 'professional practice standard' in informed consent, I will argue that an important fact in many cases is the moral integrity of the doctor concerned and the pattern of his practice. This may (...) provide the only morally principled and legally accessible evidence enabling a correct decision to be made in a difficult case. Although the epistemological significance of a professional practice standard is thereby defended the 'prudent patient standard' for what counts as consent is left intact. (shrink)

The purpose of this study is to determine the relative frequency of course offerings on social issues and business ethics in American business schools. Specifically, a random sample of the curricula of 119 American business schools were analyzed in order to gauge the importance given to coursework on ethics and social issues. The findings indicated that the incidence of such courses was generally low in American business curricula, particularly at the graduate level. These findings are discussed in light of the (...) current concern for more responsible corporate behavior. (shrink)

§ 21. Until a few years ago the hope of the physicist seems on the whole to have been that he would eventually be able to exhibit a single interconnected system of perfectly deterministic causal laws. He took the relation of cause and effect in all change to be such that from a determinate antecedent state of that which changes there must necessarily follow a different subsequent state of it, and it was assumed by him that complete knowledge of the (...) antecedent state must enable exact prediction of the subsequent state. I do not think it matters here whether that which changes was taken as a limited subject of change or as the whole physical world. (shrink)