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)

Gert H. Müller The growth of the number of publications in almost all scientific areas,· as in the area of (mathematical) logic, is taken as a sign of our scientifically minded culture, but it also has a terrifying aspect. In addition, given the rapidly growing sophistica tion, specialization and hence subdivision of logic, researchers, students and teachers may have a hard time getting an overview ofthe existing literature, partic ularly if they do not have an extensive library available in their (...) neighbourhood: they simply do not even know what to ask for! More specifically, if someone vaguely knows that something vaguely connected with his interests exists some where in the literature, he may not be able to find it even by searching through the publications scattered in the review journals. Answering this challenge was and is the central motivation for compiling this Bibliography. The Bibliography comprises (presently) the following six volumes (listed with the corresponding Editors): I. Classical Logic W. Rautenberg II. Non-c1assical Logics W. Rautenberg IH. Model Theory H. -D. Ebbinghaus IV. Recursion Theory P. G. Hinman V. Set Theory A. R. Blass VI. ProofTheory; Constructive Mathematics J. E. Kister; D. van Dalen & A. S. Troelstra. (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)

The concept of viewing historical change as a cyclical process is analyzed, beginning with the works of Polybius, historian of the Roman empire, and ending with Machiavelli, with an examination of the biblical concept of historical change.

Mill's feminism has been attacked as being logically incoherent. The general verdict has been that Mill can easily be defended from the charge. However, both sides in the debate have ignored the fact that his feminism is part of a broader theory of liberal empiricism. Placing The Subjection of Women in this context re–opens the question of its logical credentials and reveals a basic weakness in Millian feminism.

The principles of historical materialism involve Marx in making two crucial claims about freedom. The first is that the revolutionary proletariat is, in an important sense, more free than its class antagonist the bourgeoisie. The second is that the beneficiaries of a successful proletarian revolution—the members of a solidly established communist society—enjoy a greater freedom than even proletarians engaged in revolutionary praxis. It is perhaps natural to take Marx to be operating here with what might be called a logically continuous (...) notion of freedom, established communists enjoying to perfection (or as near as maybe) what revolutionary proletarians merely imperfectly experience and what the bourgeoisie entirely misses. But whatever one's views might be about what Marx in fact says about freedom this cannot be what he ought to say for his theory of freedom to work. The kind of line Marx (and Marxists) need to take finds a significant precedent in his economics where we find a theory implying two quite distinct logical dimensions in that the principles and concepts designed to apply to the transactions of capitalism (commodity, capital, wage-labour, surplus-value, and so on) necessarily lack descriptive purchase on communist economic reality. The existence of these two dimensions, and particularly Marx's comparative silence as to the nature of the second, reflect his conviction that the transition between the two systems must be marked by a profound conceptual as well as material break. Consequently it is not unreasonable, perhaps, to look for an analogous discontinuity in his metaphysics and to expect to find two distinct varieties of freedom, the one reflecting the nature of class society, the other of human community. (shrink)

Koonin, in an article in this issue, claims that CRISPR–Cas systems are mechanisms for the inheritance of acquired adaptive characteristics, and that the operation of such systems comprises a “Lamarckian mode of evolution.” We argue that viewing the CRISPR–Cas mechanism as facilitating a form of “directed mutation” more accurately represents how the system behaves and the history of neoDarwinian thinking, and is to be preferred.

Despite the significant contribution of cognitive-behavioral therapy to effective treatment options for specific syndromes, treatment progress has been stagnating, with response rates plateauing over the past several years. This stagnation has led clinical researchers to call for an approach that instead focuses on processes of change and the individual in their particular context. Process-based therapy is a general approach representing a model of models, grounded in evolution science, with an emphasis on idiographic methods, network models of case conceptualization, and enhancing (...) wellbeing. In this paper, we describe the theory underlying PBT and present a case study for how to apply PBT tools and principles to deliver process-informed and person-centered evidence-based treatment. In addition, we discuss lessons learned from our case and provide suggestions for future considerations when implementing PBT in clinical settings. (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)