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)

Según una sofisticada versión del llamado rule of law, las reglas del derecho deben ser generales, en el sentido de que deben regular clases de casos, no situaciones particulares. La posibilidad de prever cuáles van a ser las decisiones jurídicas depende, entre otras cosas, de este carácter general de las normas. Pero junto a la previsibilidad y certeza que aporta, el carácter general de las reglas puede tener un reverso negativo: en algunas ocasiones, cuando se aplican a algunas circunstancias particulares, (...) lo que parecía funcionar de forma satisfactoria en la teoría o en abstracto, proporciona soluciones inadmisibles (inadmisibles con arreglo a alguna concepción de la justicia). Esos casos son conocidos como casos recalcitrantes. En este artículo propongo una manera de entender el razonamiento jurídico-práctico que mitiga ese reverso negativo de las reglas generales conservando buena parte de la certeza que aportan. (shrink)

In this article we discuss the political thought of the French philosopher Simone Weil. In particular, we analyse two fundamental elements of her critique of Marxism, namely her reflections on the phenomenon of power and her critique of the theory of the unlimited development of productive forces. We do so in dialogue with two of the pioneers of the ecosocialist critique of Marx in Spain: Manuel Sacristán and Francisco Fernández Buey, both readers of Weil. The aim: to point out the (...) relevance of this philosopher’s thought not only for its influence on some of the great ethical-political reflections of the socialist tradition in the twentieth century, but also for its ability to address the current challenges. (shrink)

A script concordance test was developed as an innovative tool for assessing ethical reasoning ability. An SCT of 12 medical ethical vignettes were constructed from the UNESCO Casebook on Human Dignity and Human Rights. The vignettes were reviewed by a panel of 15 medical experts before administration to a panel of 18 clinicians. The clinician’s answers were used to constitute the scoring key. The SCT was then administered to first and final year medical students. Data were analysed using SPSS. Internal (...) consistency was assessed using Cronbach’s alpha. SCT performance was tested for association with sex, year of study and race by comparing the mean SCT scores between categories within each variable. Internal consistency as measured by Cronbach’s alpha values, ranging from 0.597 to 0.902, indicated high intra-vignette reliability for 10 of the vignettes. Inter-vignette reliability was high at 0.797. Mean SCT scores were not significantly different between students of different gender, year of study and ethnicity. However, each vignette was able to distinguish between overall poor and good test performers. The SCT was able to differentiate between students with varying degrees of ethical reasoning ability. (shrink)

Este artículo explora la posibilidad de que las constituciones contemporáneas puedan ser interpretadas de manera armónica, es decir, irenista. Las objeciones más importantes a las que una concepción irenista de la constitución debería hacer frente son las objeciones de la incoherencia y de la inestabilidad. La primera afirma que la armonía no es posible porque se dan conflictos normativos entre los diversos componentes de las constituciones contemporáneas. La segunda afirma que no es posible una armonía de tipo universalista. Una concepción (...) irenista con visos de ser plausible debería poder ser capaz de dar una respuesta a cada una de estas objeciones. (shrink)

Desarrollamos un análisis comparativo de las vivencias del dolor físico y de la imaginación desde la perspectiva fenomenológica. Partimos de la hipótesis de que ambas vivencias forman los estados límite de la vida consciente. Nuestro objetivo es mostrar las características esenciales de dichas vivencias y para ello seguimos los textos más relevantes de la tradición fenomenológica, especialmente los de Husserl y Sartre. Los de Husserl dedicados al cuerpo vivido y a las sensaciones táctiles, por un lado, y los dedicados a (...) la conciencia de imagen y a la fantasía, por el otro, son totalmente imprescindibles, y los complementamos con los de Sartre dedicados a la imaginación. Recurrimos también a estudios fenomenológicos actuales sobre ambas vivencias. En primer lugar describiremos la vivencia del dolor físico como una auto-afección que en casos de dolor severo destruye el fundamento de la constitución de sentido que es el cuerpo vivido. En segundo lugar, describiremos la imaginación (o fantasía) como la reproducción de una experiencia posible. La conciencia como auto-afección es opuesta a la conciencia como reproducción de modo que, efectivamente, ambas forman los limites extremos de la conciencia humana como subjetividad encarnada. (shrink)

El propósito de este artículo es discutir la posibilidad y tarea de la estética bajo un enfoque fenomenológico. Nos centramos en la arquitectura, de la cual analizamos su estructura estratificada, siguiendo los análisis de Roman Ingarden, y la especificidad de la actitud estética, frente a otras actitudes que también reclama la arquitectura, según las observaciones de Paul Valéry. Planteamos finalmente la cuestión central acerca de la posibilidad de la comprensión del arte en general y de la arquitectura en particular comparando (...) la estética fenomenológica con la estética de la negatividad. (shrink)

The debate concerning the so-called U.S. Health and Human Services Contraception Mandate has been adequately framed, in the academic field, within the traditional ethical doctrine on cooperation with evil. This principle will allow us to conclude whether employers may ethically comply with the onerous existing law or not. The discussion has been quite heated, because the practical conclusions authors have reached vary widely, depending on which interpretation of the theory they rely on. In this paper, some of these explanations are (...) addressed and analyzed from the standpoint of the Thomistic theory of action, which is now the most common point of view. This work concludes that, although the Contraception Mandate will most likely be repealed by the current U.S. administration, as things once stood, compliance with it may have been ethically licit in some cases. (shrink)

This book explores secession from three normative disciplines: political philosophy, international law and constitutional law. The author first develops a moral theory of secession based on a hypothetical multinational contract. Under this contract theory, injustices do not determine the existence of a right to secede, but the requirements to exercise it. The book’s second part then argues that international law is more inclined to accept and advance a remedial right approach to secession. Therefore, justice as multinational fairness is to be (...) fully institutionalized under the constitutional law of liberal democracies. The final part proposes constitutionalizing a qualified right to secede with the aim of fostering recognition and accommodation of national pluralism as well as cooperation and compromise between majority and minority nations. (shrink)

This paper is divided into two main parts. In the first half, I identify a tension within Bernard Williams’ political realist conception of political legitimacy. On the one hand, he was committed to a peculiar universalist criterion of political legitimacy – what is politically unacceptable is summed up in the old Catholic saying quod semper, quod ubique, quod ab omnibus creditum est. On the other, he supported the idea that what counts as political legitimacy depends on what we, in the (...) here and now, deem to be politically legitimate – thus suggesting some kind of relativist criterion for political legitimacy. In order to eliminate this tension, I propose a two-step reconstruction of Williams’ works on political philosophy. The second half of the article assesses three criticisms to Willliams’ conception of political legitimacy levied by contemporary political realists. I use my two-step reconstruction of Williams to reject two of these three objections. In addressing the third, I sketch a reading of Williams’ notion of political legitimacy in the context of his ethical project as a whole and, in so doing, overcome the difficulty. (shrink)

Early Christian writers defined idolatry around the monotheistic distinction between proper worship of the creator and vain worship of the creature, which they had inherited from Hellenistic Judaism. Despite the remarkable consensus about the validity of this theological analysis, the medieval synthesis was under severe strain throughout the early modern period, mainly because of the concept's extended range of application in the new contexts of religious controversy. In all these cases, deciding what practices constituted idolatry was open to debate. By (...) the eighteenth century, libertine writers could retain the concept of superstition at the expense of that of idolatry, which Voltaire (himself an anti-Christian deist) denounced as meaningless. (shrink)

El contenido de este artículo consiste en mostrar que la experiencia estética es la esencia de la experiencia de la obra de arte. Argumentaré en contra de la concepción del arte de Arthur C. Danto según la cual el arte moderno ya no requiere de la experiencia estética y este hecho determina el fin del arte. La experiencia estética permitiría dar cuenta del arte desde el Renacimiento hasta el siglo XIX pero el arte moderno del siglo XX solo puede ser (...) explicado conceptualmente y, por tanto, la filosofía del arte es necesaria para explicitar ese contenido.Para defender el estatuto estético de la obra de arte mostraré que la experiencia estética se identifica con la experiencia fenomenológica. Esto quiere decir que la experiencia estética nos hace concientes de la diferencia entre el contenido de la obra y el medio de la experiencia sensible en el que este contenido se da. El “aparecer” y “lo que aparece” se corresponden en la experiencia estética con los dos polos de la relación intencional y constituyen los dos estratos fundamentales de la obra de arte. A través de la aproximación fenomenológica intentaré mostrar que la obra de arte no excluye el contenido conceptual, pero este contenido ha de estar necesariamente incorporado. No es la filosofía la que tiene que comprender este contenido sino exclusivamente la experiencia estética.The subject of this paper is to claim that the aesthetic experience is the essence of the experience of the work of art. I argue against the view hold by Arthur C. Danto, according to which modern art does not require the aesthetic experience any more and that this fact means the end of art. The aesthetic experience allows explaining only the art made be-tween the Renaissance and the XIX century. The modern work of art of the XX century can only be explained conceptually and therefore a philosophy of art is required to make that content explicit and clear.To defend the aesthetic status of the work of art I will show that the aesthetic experience identifies itself with the phenomenological ex-perience. This means that the aesthetic experience makes us aware of the difference between the content of the work and the sensible lived experience in which this content appears. The “appearance” and “what appears” are the two poles of Intentionality and the two fundamental layers of the work of art. Through the phenomenological approach I will make clear that the work of art does not exclude the conceptual content at all. This content has to be necessarily embodied. It is not philosophy that has to disclose this con-tent but the aesthetic experience alone. (shrink)

Timothy Williamson defensa que la filosofia és una ciència teòrica que s’ocupa d’investigar sobre la realitat, d’obtenir coneixement, i que ho fa construint teories, confrontant-les amb l’evidència, d’una manera sistemàtica, disciplinada i socialment organitzada, com les altres ciències. En aquest article es compara aquesta posició, d’una banda, amb la que considera que la filosofia és una reflexió de segon ordre sobre la ciència, la moral, la política, l’art…; i, de l’altra, amb la concepció de la filosofia com a guia de (...) la vida, com a recerca de la saviesa pràctica. (shrink)

Phenomenology is often described as a paradigm shift that calls for a re-assessment of inherited themes and concepts. One of its most important contributions is the central role given to the embodied subject as opposed to the conception of the disembodied subject that has dominated philosophy since Descartes. If perspectival painting best represents the paradigm of modern philosophy since the Renaissance, it is the multiple perspectives of Cubist painting that best represent the phenomenological paradigm. While the relationship between phenomenology and (...) art has been widely studied, my aim in this article is to focus on the way in which Cubism represents the embodied, horizonal structure of our perception, and then to discuss the new form of contemporary art installation as an actualization of Cubist principles in the age of digital reproduction. The embodiment of the subject necessarily involves intersubjectivity, for others appear in the subject’s contextual frame of public space. While for Arendt the shift from private subjective space to public intersubjective space is effected through dialogue, I argue that it is also effected architecturally, for architecture facilitates dialogue by offering multiple perspectives on common space and shared time. I suggest, finally, that architecture’s multiperspectival strategies offer the humanities a useful model of a multidisciplinary methodology. (shrink)

India and its religion played an important role in the assault on Christian orthodoxy during the late Enlightenment. However, the late-seventeenth century transition from antiquarian apologetics to libertinism is harder to explain, and yet historically more crucial. This chapter maps this process with particular reference to the interpretation of the remarkable range of materials concerning Hinduism that appeared in the illustrated encyclopedia of world religions Cérémonies et coutumes de tots les peuples du monde. Its editor, Jean-Fréderic Bernard, went well beyond (...) the mere task of compilation and publication, and his interpretative choices, colored by a rationalist form of Deism, often departed from the differing agendas present in his sources. On the basis of considering these differences, this chapter seeks to elucidate how exactly the shift from comparative antiquarian apologetics to a comparative libertine anthropology of religion took place and analyzes its implications for the religious culture of the Enlightenment. (shrink)

L'étude aborde la question de la méthode théologique, en considérant sa nature et sa typologie, ses possibilités et ses limites, ainsi que les conditions de sa légitimité devant les instances du «depositum fidei». On attribue une importance spéciale à la tension de fond entre l'usage de la méthode kérygmatique et de la méthode dialogale dans la théologie du passé, mais surtout dans le débat actuel, spécialement entre divers courants de la théologie de la transcendance, telles les «théologies de la parole» (...) et la «méthode de corrélation», ou encore entre les «théologies du mystère» et la «méthode transcendantale». Pareille tension s'aggrave dans les «théologies de l'immanence», telles les théologies de la «mort de Dieu» ou les «théologies de l'histoire», ou entre les «théologies de la modernité» et certaines «théologies de la praxis». A la fin de ce panorama du pluralisme méthodologique actuel, on formule certains principes fondamentaux sur le problème débattu. Finalement, on considère le caractère obligatoire du «depositum fidei» comme instance théologique définitive. (shrink)