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 lieu of an abstract, here is a brief excerpt of the content:BOOK REVIEWS 741 pointedly, what he is asking for is " the ' planned dissolution ' of the Latin Church into a considerable number of distinct, autonomous ' patriarchates ' " (p. 132). These suggestions, although not original, are intriguing. They deserve, however, more than three pages. What is needed is a detailed presentation of these changes, indicating their historical context, their advantages and disadvantages, and their practical implementation. (...) Despite the criticisms given above, there is much good material to be found in this crisply written book. I agree in general with Hill's judgment that Church authority should embody a collegial rather than a monarchical ecclesiology. He shows that the MC ecclesiology has a solid foundation in scripture and tradition and its cornerstone is the theology of the local Church. Furthermore, he is correct in insisting that the doctrines of collegiality and the priesthood of the faithful are urgent questions in contemporary ecclesiology and that they have broad ecumenical ramifications. He speaks convincingly of greater lay participation, local autonomy, consultation, and accountability. At the same time, his partisanship leads him to caricature the MP view. He will not persuade many MP supporters by criticizing their "highhanded authoritarianism and paternalism " (p. 53) and " ecclesiastical dishonesty " (p. 127) or by claiming that the Roman Curia " is neuro· tically obsessed with the matter of papal authority" (p. 114). Hill makes many valid and important points, but, on occasion, he weakens them by exaggeration. At times his partisan style overcomes his theo· logical substance. The Catholic University of America Washington, D.C. pATRICK GRANFIELD Many Paths: A Catholic Approach to Religious Pluralism. By EUGENE HILLMAN. Maryknoll, New York: Orbis Books, 1989. Pp. 95. A Christian theology of religions raises fundamental epistemological and methodological questions. Hillman comes to the debate from what Lindbeck has called an " experiential expressivist " background, that is, there is a tacit assumption that reality is experienced and then expressed, that reality precedes language rather than being disclosed and shaped through language. When such an outlook is applied to the theology of religions, the outcome is often the " discovery " of a common experience underlying all religions, despite their different expressions. The latter can be seen to vary according to climate, history, temperament, and so on. Such expressions are loose symbols for a 742 BOOK REVIEWS greater reality, which takes on an increasingly vague shape with the demise of the signifier. History can offer very little resistance to such a model, and the conflicts, differences, intractabilities, and real problems of religious plurality are slowly silenced, almost numbed into a drowsy calm. That history refuses to play this role, while theologies of religion are often demanding it, is indicative of the difficulties with such a model. Hillman's first book on this topic (The Wider Ecumenism, 1968) showed him to be a follower of Rahner. He stressed the universality of grace and its mediation through the historical and particular; he thereby argued for a wider ecumenism with regard to the world religions, in a model analogous to intra-Christian ecumenism. In this book, Hillman advances the same position, but now infused with a strong dose of Wilfred Cantwell Smith. He does not confront the theological criticisms made against either of his mentors. The book is divided into four lucid chapters. The first considers the meaning and role of religion, and much of Hillman's discussion is helpful. However, as the chapter proceeds, one finds that the definition of religion is not controlled by the particularities and intractable dif. ferences presented by the subject matter but rather by an experiential essentialism. Hillman uses Smith's distinction between "faith" and " belief " to two ends, one descriptive, the other evaluative. However he, like Cantwell Smith, conflates description with evaluation. Furthermore, he is untroubled that the subject matter under inspection does not easily yield to such distinctions. Descriptively, " belief " or the " cumulative tradition " involves the " myriad historico-cultural par· ticularizations " that go to make up a religion such as liturgies, doc· trines, ethical systems, practices, histories, and so on {20). Faith is basically an experience of " the tr,anscendent, which is presumably the same for every person," and can be distinguished from the "cumulative tradition, which is different for each people, nation or... (shrink)

In lieu of an abstract, here is a brief excerpt of the content:TAKING OTHER RELIGIONS SERIOUSLY: SOME IRONIES IN THE CURRENT DEBATE ON A CHRISTIAN THEOLOGY OF RELIGJ:ONS * 1GAvIN D'CosTA West London Institute of Higher E'ducation Isleworth, Middlese111 HE QUESTION oi Christian attitudes to the world eligions is becoming increasingly important. An lnterpretatwn of Religion is emblematic of a growing trend, which runs across 1denominational lines, that attempts fo take other,religions seriously. John Hick.argues that for most of its ihistory (...) Christianity has hrud a rpolitioaUy and theologicrully imperialist attitude towards the ireligions of the world. Superiority :and uninformed arrogance have generally prev:ailed with the accompanying attitude that the religions of the world 1aire 1 generally sinful and incapable of being 1 salvific. The 1 time has come foT a change of a;ttitude: the wol"ld reHgions must be taken seriously :and this means ·affil"ming them as alternative paths to salvation, possibly neither worse nor better than·Christianity. This Hick cru1ls a "pluralistic" outlook. The agenda is irrudical and Hick's Vioice is not solitary. Hick'1 s hook!is a ma;gisteri:al 4rn paiges and is ibrused on his Giffol'ld Lectmes of 1986-87. It contains cons!i.derruble indological, philosophicail and theological material, hut in what follows I shall,be dea1ing with one aspect oll!ly, his argument for p1uiialism. Hick is acknowledged :as a leading irepresentative of this pluralistic approach. Initially he began as a conservative,and exclusivist Christian,and has over the years enoompassed a wide!l.'ange of thoofogica1 positions now,culminating *John Hick, An Interpretation of Religion: Human Responses to the Transcendent (New Haven: Yale University Press, 1989). 519 520 GAVIN D'COSTA in this p11esent rbook.1 In :this review discussion I propose that many o[ the most mdical strategies in the theology of re1ligions in 'Spite 0£ their wish to take other rreligions seriously have an il'!Onic tendency to do just the opposite! In attempting to be genuinely accommodating to the 11eligions 0£ the world, Hick, I will argue, unwittingly ends up in danger of accommodating none, including Christianity. This tendency, which iI believe to 1be clearly illustrated in Hick's rrecent rbook, is shared in various degrees hy numerous theologians pursuing a, pluralist p111oject similar to that of Hick's.2 It would he foolish to assume they are " all the 'Saime," hut they certainly share common theological and philosophical tendencies which I wish to isolate and comment on. I should 1state dearly that iby such a critique I do not intend to discount the possibility that 1 a:ll religions ma,y lead fo God, but that the stmtegies often employed to a111g111e.for this are deepJy problematic. ~o put Hiok"s new rbook into :perspective it will he helpful to wace its genesis 1briefly. In 1973, using an astronomical analogy, Hick suggested a Copernican revolution in the Christian theoology of rreligions whereby Christians should "shift from the 1 He began, in his own words, as a "strongly evangelical and indeed fundamentalist " Christian: see God Has Many Names (London: Macmillan, 1980), p. 2. See also my analysis of his entire pilgrimage in John Hick's Theology of Religions (London/New York: University Press of America, 1987). 2 For some of those on Hick's trajectory, see A. Race, Olllristians and Religious Pluralism (London: SCM, 1983); Paul Knitter, No Other Name'! (New York: Orbis, 1985); Wilfred Cantwell Smith, The Meaning and End of Religion (New York: Harper & Row, 1978); R. Ruether, Pluralism and Ohristology; the latter three and other influential co-contributors (including Hick) are to be found in The Myth of Christian Uniqueness: Towards a Pluralistio Theology of Religions, ed. J. Hick and P. Knitter (New York: Orbis, 1987). More recently, we can see the extremely thin line between pluralists and essentialist "inclusivists" in E. Hillman, Many Paths·: A Oatholic Approach to Religious Pluralism (New York: Orbis, 1989), who marries K. Rahner and W. C. Smith, divorces faith from history and tradition, and thereby provides an essentialist analysis. See the pertinent comments of K. Surin on Smith's essentialist project in "An Examination of the Discourse of John Hick and Wilfred Cantwell Smith", in Religious Pluralism and Unbelief, ed. I. Hamnett (London, Routledge... (shrink)

Horace, Janus, and Pighius' Acta In PBSR 54 , 213–28 Andrew Lintott dusts down the fragments of the Acta Urbana published by S. V. Pighius in 1615 and universally supposed today to be a forgery. Lintott himself, after a most learned discussion, concurs, but one senses a wistful longing for the fragments to be genuine. The purpose of this note is to offer another reason why sadly this is unlikely.

Two categories of life are currently recognized—chemosynthetic and photosynthetic—indicating their principal free energy resource as either chemicals or electromagnetic radiation. Building on recent developments in thermodynamics, we posit a third category of life—thermosynthetic life (TL)—which relies on environmental heat rather than traditional free energy sources. Since thermal energy is more abundant than chemicals or light in many settings, thermosynthesis offers compelling evolutionary possibilities for new life forms. Based on variants of standard cellular machinery, a physical model is proposed for the (...) conversion of thermal energy into biochemical work. Conditions favorable to thermosynthetic life and prospects for its discovery are assessed. Terrestrially, deep-subsurface unicellular anaerobic superthermophiles are deduced to be likely TL candidates. (shrink)

No one should be put off from reading Miles' Logik undMetaphysik bei Kant by his telling us that he is following the ‘phenomenological-philological method’ Heidegger practiced, as shown in his Phenomenological Interpretation of Kant's Critique of Pure Reason, his earliest work on Kant and his last to be published. I do not claim to understand Miles' conception of this method. Whatever it be, what Miles actually presents is a careful examination of a number of crucial passages in Kant's first Critique (...) in Kantian terms. From it even the most seasoned student of the Critique will find light. (shrink)

I shall unfold Kant’s views on three topics. Kant holds that knowledge of anything’s existence is obtained only by existential judgments. He distinguishes several respects in which the predicate of such a judgment differs from other predicates. In the light of these, Kant sets forth what is required for verifying existential judgments.

Many medical ethicists accept the thesis that there is no moral difference between withholding and withdrawing life-sustaining therapy. In this paper, we offer an interesting counterexample which shows that this thesis is not always true. Withholding is distinguished from withdrawing by the simple fact that therapy must have already been initiated in order to speak coherently about withdrawal. Provided that there is a genuine need and that therapy is biomedically effective, the historical fact that therapy has been initiated entails a (...) claim to continue therapy that cannot be attributed to patients who have not yet received therapy. This intrinsic difference between withholding and withdrawing therapy is of moral importance. In many instances, patients will waive this claim. But when one considers withdrawing therapy from one patient to help another in a setting of scarce resources, this intrinsic moral difference comes into sharp focus. In an era of shrinking medical resources, this difference cannot be ignored. (shrink)

A recently formulated concept of stochastic localizability is shown to be consistent with a concept of stochastic microcausality, which avoids the conclusions of Hegerfeldt's no-go theorem as to the inconsistency of sharp localizability of quantum particles and Einstein causality. The proposed localizability on quantum space-time is shown to lead to strict asymptotic causality. For finite time evolutions, upper bounds on propagation to the exterior of stochastic light cones are derived which show that the resulting probabilities are too small to be (...) actually observable in a realistic context. (shrink)

The empirical level of research in the experimental sciences always involves description of what is found by observation and experimentation. These descriptions most often take the form of tables of various sorts . In the process of compiling tables of functions, the method of smoothing-out data plays a significant role. It is often performed by graph procedures. This work results in the formulation of laws, general relationships, which are clothed, in mathematical natural science, in the form of empirical or semi-empirical (...) equations. (shrink)

Little is known about distance processing in patients with posterior brain damage. Although many investigators have claimed that distance estimates are normal or abnormal in some of these patients, many of these observations were made informally and the examiners often asked for relative, and not absolute, distance estimates. The present investigation served two purposes. First, we wanted to contrast the use of distance information in peripersonal space for perceptual report as opposed to visuomotor control in our visual form agnosic patient, (...) DF. Second, we wanted to see to what extent her abilities to process distance cues were dependent on binocular vision, in light of Milner et al.'s (1991) observations of preserved stereopsis in DF, and Dijkerman et al.'s (1996) and Marotta et al.'s (1997) observations that her visual guidance of grasping may be particularly dependent on binocular vision of the target. We hypothesized that DF's visuomotor responses would show normal sensitivity to target distance, while her perceptual estimates would not. In the first experiment, we required DF and two age- and sex-matched control subjects to reach out and grasp black cubes placed at varying distances, or to estimate the distance of the cubes from the hand starting position without making a reaching movement. In the second experiment, we required DF and two age-matched control subjects to point as rapidly and accurately as possible to small LED targets which differed in spatial location, under binocular and monocular conditions. The results showed that, relative to the control subjects, DF's grasping movements produced normal peak velocity-distance scaling-when she reached for blocks which varied in depth or pointed to LED targets which were presented at different distances in depth. In contrast, in the cube experiment, her verbal estimates of object distance were poorly scaled, although they improved slightly under the binocular conditions. The results are discussed in terms of current theories of processing streams in extrastriate visual cortex and the distinction between categorical and coordinate spatial processing. (shrink)

The introduction of conscience clauses after the 1973 US Supreme Court decision in Roe v. Wade allowed physicians and nurses to opt out of medical procedures, particularly abortions, to which they were morally opposed. In recent years pharmacists have requested the same consideration with regard to dispensing some medicines. This paper examines the pharmacists’ role and their professional and moral obligations to patients in the light of recent refusals by pharmacists to dispense oral contraceptives. A review of John Rawls’s concepts (...) of the “original position” and the “veil of ignorance”, along with consideration of the concept of compartmentalisation, are used to assess pharmacists’ requests and the moral and legal rights of patients to have their prescriptive needs met. (shrink)

A laboratory-testable, solid-state Maxwell demon is proposed that utilizes the electric field energy of an open-gap p-n junction. Numerical results from a commercial semiconductor device simulator (Silvaco International–Atlas) verify primary results from a 1-D analytic model. Present day fabrication techniques appear adequate for laboratory tests of principle.

To define knowledge in terms of (i) belief, (ii) justification, and (iii) truth is primarily epistemological and therefore seems to be untenable. What is wrong with the ontological view of knowledge? If objects like dream and shadow could be said to be real and worth investigating, why should knowledge itself not be treated as a knowable reality? Knowability suggests its possibility-like, pursuit-like, gradual disclosive—as distinguished from enclosed or complete—character. Disclosure isself-revealing or, as Indians say, svaprakasa. That is, its justification arises (...) from within. (shrink)

Background and methods: Psychiatric research can occasionally present particular ethical dilemmas, but it is not clear what kind of problems local research ethics committees actually experience in this field. We aimed to assess the type of problems that committees encounter with psychiatric research, using a postal survey of 211 LRECs.Results: One hundred and seven of those written to replied within the time limit. Twenty eight experienced few problems with psychiatric applications. Twenty six emphasised the value of a psychiatric expert on (...) the committee. The most common issues raised were informed consent and confidentiality . The use of placebos , the validity of psychiatric questionnaires and overuse of psychiatric “jargon” in psychiatric applications also raised concern.Conclusions: Our results suggest that LRECs have specific concerns regarding methodology, consent, and confidentiality in psychiatric research, and that they find psychiatric input invaluable. (shrink)