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)

Since the middle of the 20th century, suicidology, as a group of disciplines working to understand and prevent suicide, has reinforced the long-held view that suicide is caused first and foremost b...

Summary Using the neurological syndrome kuru as a frame, Warwick Anderson examines the social dynamics and material culture of its medical investigation among the Fore people conducted by D. Carleton Gajdusek beginning at midcentury. The Collectors of Lost Souls: Turning Kuru Scientists into White Men uses a postcolonial framework to complicate dominant/subordinate binaries and diffusionist accounts of indigenous contacts with medical science. Anderson proposes that colonies are specific sites of production of medical knowledge. He draws a distinction between traditional and (...) advanced economies in regard to individual rights to make an argument in support of context-specific ethical regulation for medical research and suggests a role for historians of science in interrogating the process of globalisation. (shrink)

James I. The Political Works of James I. Reprinted from the Edition of 1616. With an Introduction by Charles Howard McIlwain. Cambridge: Harvard University Press, 1918. cxi, 354 pp. Reprinted 2002 by The Lawbook Exchange, Ltd.

Summary Watters questions the universality of mental illness and warns of the harms that accompany the exportation of Western typologies to non-Western cultures. He is particularly concerned that these effects will be exacerbated by the upcoming revisions of the Diagnostic and Statistical Manual of Mental Disorders (DSM-V). Building on his examination of non-Western practices, Watters exposes the historical instability of mental health classifications in North America to question the validity of current DSM categories. Although Watters' warnings about the dangers of (...) the globalisation of the DSM are persuasive, they may be overreaching as our examination of the successful incorporation of Western created autism services, information, and interventions in the developing world suggests. (shrink)

In El Salvador from 1978 to 1988, contraceptive use among married women 15–44 years of age increased from 34% to 47%, and the total fertility rate declined from 6·3 to 4·6 children per woman. Most of this change took place from 1978 to 1985. Sterilization is the most prevalent method used, but nearly one-half of the women who are sterilized did not use any contraception before their operation. Few young couples use reversible methods of contraception to space births or delay (...) the start of childbearing. On average, women wait 8 years after marriage and have nearly three children before they use contraception. (shrink)

Employing the National Institute of Mental Health-funded Prevention of Suicide in Primary Care Elderly Collaborative Trial as a case study, we discuss 2 sets of ethical issues: obtaining informed consent for a clinic-based intervention study and using treatment as usual (TAU) as the control condition. We then address these ethical issues in the context of the debate about the quality improvement efforts of health care organizations. Our analysis reveals the tension between ethics and scientific integrity involved with using TAU as (...) a control condition and the difficulty in designing high-quality research in a community-based setting. (shrink)

Although sensorimotor contingencies may explain visual perception, it is difficult to extend this concept to speech perception. However, the basic concept of perception as active hypothesis testing using attention does extend well to speech perception. We propose that the concept of sensorimotor contingencies can be broadened to sensory-attentional contingencies, thereby accounting for speech perception as well as vision.

There is considerable evidence that the hippocampal system contributes both to (1) the temporary maintenance of memories and to (2) the processing of a particular type of memory representation. The findings on amnesia suggest that these two distinguishing features of hippocampal memory processing are orthogonal. Together with anatomical and physiological data, the neuropsychological findings support a model of cortico-hippocampal interactions in which the temporal and representational properties of hippocampal memory processing are mediated separately. We propose that neocortical association areas maintain (...) shortterm memories for specific items and events prior to hippocampal processing as well as providing the final repositories of long-term memory. The parahippocampal region supports intermediate-term storage of individual items, and the hippocampal formation itself mediates an organization of memories according to relevant relationships among items. Hippocampal-cortical interactions produce (i) strong and persistent memories for events, including their constituent elements and the relationships among them, and (ii) a capacity to express memories flexibly across a wide range of circumstances. (shrink)

The first full-length study in English of Gassendi's life and work. I. The Man and his Work - II. Gassendi the Critic (separate chapters devoted to the Aristoteleans, Herbert of Cherbury and Descartes) - III. Gassendi the Philosopher. (Bibliotheca Humanistica & Reformatorica, Vol. XXXIV).

Faith in God conflicts with reason—or so we’re told. We focus on two arguments for this conclusion. After evaluating three criticisms of them, we identify an assumption they share, namely that faith in God requires belief that God exists. Whether the assumption is true depends on what faith is. We sketch a theory of faith that allows for both faith in God without belief that God exists, and faith in God while in belief-cancelling doubt God’s existence. We then argue that (...) our theory, unlike the theory of Thomas Aquinas, makes sense of four central items of faith-data: (i) pístis in the Synoptics, (ii) ʾemunāh in the Hebrew scriptures, (iii) exemplars of faith in God, including Abraham, Jesus, and Mother Teresa, and (iv) the widespread experience of people of faith today. We close by assessing revisions of the two arguments we began with, revisions that align with our theory of faith, and find them dubious, at best. (shrink)

This paper is concerned with the implication from value to fittingness. I shall argue that those committed to this implication face a serious explanatory challenge. This argument is not intended as a knock-down argument against FA but it will, I think, show that those who endorse the theory incur a particular explanatory burden: to explain how counterfactual favouring of actual value is possible. After making two important preliminary points I briefly discuss an objection to FA made by Krister Bykvist a (...) few years ago. The point of discussing this objection is to enable me to more easily present my own, and I believe stronger, version of that objection. The overall argument takes the form of, simply, a counterexample which can be constructed on the back of of my two preliminary points. Throughout the paper I try to respond to various objections. (shrink)

In this chapter I defend a methodological view about how we should conduct substantive ethical inquiries in the fields of normative and practical ethics. I maintain that the direct plausibility and implausibility of general ethical principles – once fully clarified and understood – should be foundational in our substantive ethical reasoning. I argue that, in order to expose our ethical intuitions about particular cases to maximal critical scrutiny, we must determine whether they can be justified by directly plausible principles. To (...) expose apparently plausible principles to maximal critical scrutiny, we must determine whether their direct plausibility can survive careful clarification of what they are really saying. This means that intuitions about cases are useful only in (a) suggesting principles that must stand on their own two feet, and (b) illustrating or otherwise helping us clarify what a principle is really saying. We should not reject principles that seem most directly plausible after we have fully clarified their content simply because they conflict with our intuitions about cases, because to do so is to side with uncritical prejudices over the teachings of critical scrutiny. (shrink)

The New Zealand philosopher, Robert Nola (1940-2022), has died. He was a kind man, a good friend, and a fine philosopher. Here is how I remember him.

Can we ever be fully practically justified in acting contrary to moral demands? My contention is that the answer is 'no'. I argue that by adopting a 'buck-passing' account of wrongness we can provide a philosophically satisfying answer to the familiar 'why should I be moral?'. In working my way toward the buck-passing account of wrongness, I outline the metaethical and 'metanormative' assumptions on which my theory stands. I also consider and reject the 'internalist' answer to 'why should I be (...) moral?'. The account I end up with is decidedly non-consequentialist and it is consistent with common-sense morality. It also provides a way of showing why moral considerations are overridingly normative in a way that is consistent with our best current understanding of what practical reason requires of us. (shrink)

Bernard Williams has famously argued that there are only “internal” reasons for action. Although Williams has produced several, slightly different versions of internalism over the years, one core idea has remained the same: the reasons a person has for acting must be essentially linked to, derived from, or in some other way connected to, that person’s “subjective motivational set”. I have two aims in this paper. First, after having cleared up some initial ambiguities, I try to show that Williams’s internalism (...) admits of two rather different interpretations. Second, I will argue that both these interpretations are inadequate. The first interpretation is incompatible with certain claims that supposedly provide the reasons why we should accept internalism in the first place. The second interpretation faces other problems: given the essential link between reasons and motivation, this interpretation cannot adequately deal with the phenomenon of accidie. Furthermore, those who subscribe to this interpretation of internalism are, on pain of inconsistency, forced to accept an implausible account of reasonable regret. (shrink)

The World Health Organisation (WHO) is leading a global effort to deliver improved diagnostic testing to people living in low‐resource settings. A reliance on the healthcare technologies marketplace and industry, shapes many aspects of the WHO project, and in this situation normative guidance comes by way of the ASSURED criteria — Affordable, Sensitive, Specific, User‐friendly, Rapid and robust, Equipment‐free, and Delivered. While generally improving access to diagnostics, I argue that the ASSURED approach to distributive justice — efficiency — and assessment (...) of worth — productivity — may constrain efforts to deliver timely and accurate diagnosis in the developing world equitably by holding back new and innovative diagnostics and indirectly encouraging program and device design that may unfairly discriminate against certain groups. Even as we try to overcome the problem of global healthcare injustice, we may be entrenching disadvantage. I present my critique of ASSURED by 1) referencing Boltanski and Thévenot's theory of orders of worth to highlight the industrial and market foundations of the ASSURED guidelines; 2) comparing ASSURED with other normative guides that elevate the importance of civic responsibility in evaluations of distributive justice; 3) presenting a case study of the failed promise of microfluidic diagnostic devices. I conclude that a new approach to normative guidance is required to assess the value of developing world diagnostics, preferably, one that does not force global public goods into the marketplace. (shrink)

The most common form of direct realism is Phenomenological Direct Realism. PDR is the theory that direct realism consists in unmediated awareness of the external object in the form of unmediated awareness of its relevant properties. I contrast this with Semantic Direct Realism, the theory that perceptual experience puts you in direct cognitive contact with external objects but does so without the unmediated awareness of the objects’ intrinsic properties invoked by PDR. PDR is what most understand by direct realism. My (...) argument is that, under pressure from the arguments from illusion and hallucination, defenders of intentionalist theories, and even of relational theories, in fact retreat to SDR. I also argue briefly that the sense-datum theory is compatible with SDR and so nothing is gained by adopting either of the more fashionable theories. (shrink)

According to the Christian religion, Jesus was “crucified under Pontius Pilate; he suffered death and was buried. On the third day he rose again”. I take it that this rising again—the Resurrection of Jesus, as it’s sometimes called—is, according to the Christian religion, an historical event, just like his crucifixion, death, and burial. And I would have thought that to investigate whether the Resurrection occurred, we would need to do some historical research: we would need to assess the reliability of (...) the New Testament documents and related manuscripts; we would need to look into the credibility of the witnesses to his post-mortem appearances, the empty tomb, and the like. The task looks rather daunting. But, according to David Hume, we don’t have to do anything of the kind. For no matter how strong the testimony in favor of a miracle is—indeed, even if we “suppose…that the testimony considered apart and in itself, amounts to an entire proof”—we have at our disposal a “full proof…against the existence of any miracle”. So we can avoid all that tedious historical work. We can simply use Hume’s shortcut, a proof against the existence of any miracle, and hence a proof against the Resurrection. So Hume says he has a “a decisive argument,” “an everlasting check to all kinds of superstitious delusion,” superstitious delusions like the Resurrection. There is good news and bad news in Hume’s proclamation. The good news is that he really has two arguments, not just one—or, at any rate, many scholars discern in his writings two arguments. The bad news is that neither succeeds; at any rate, try as I might, I can’t see how they do. (shrink)

In this rethinking of Marxism and its blind spots, Dick Howard argues that the collapse of European communism in 1989 should not be identified with a victory for capitalism and makes possible a wholesale reevaluation of democratic politics in the U.S. and abroad. The author turns to the American and French Revolutions to uncover what was truly "revolutionary" about those events, arguing that two distinct styles of democratic life emerged, the implications of which were misinterpreted in light of the (...) rise of communism. Howard uses a critical rereading of Marx as a theorist of democracy to offer his audience a new way to think about this political ideal. He argues that it is democracy, rather than Marxism, that is radical and revolutionary, and that Marx could have seen this but did not. In Part I, Howard explores the attraction Marxism held for intellectuals, particularly French intellectuals, and he demonstrates how the critique of totalitarianism from a Marxist viewpoint allowed these intellectuals to see the radical nature of democracy. Part II examines two hundred years of democratic political life--comparing America's experience as a democracy to that of France. Part III offers a rethinking of Marx's contribution to democratic politics. Howard concludes that Marx was attempting a "philosophy by other means," and that paradoxically, just because he was such an astute philosopher, Marx was unable to see the radical political implications of his own analyses. The philosophically justified "revolution" turns out to be the basis of an anti-politics whose end was foreshadowed by the fall of European communism in 1989. (shrink)

In I 7 Aristotle lays down criteria for what is to count as human happiness. Happiness for man is self-sufficient, complete without qualification, peculiar to humans, excellent, and best and most complete. Many interpreters agree that in X 6–8 Aristotle uses these along with other criteria to disqualify the life of amusement and rank one happy life above another.

In I 7 Aristotle lays down criteria for what is to count as human happiness. Happiness for man is self-sufficient , complete without qualification , peculiar to humans , excellent , and best and most complete . Many interpreters agree that in X 6–8 Aristotle uses these along with other criteria to disqualify the life of amusement and rank one happy life above another.

In this rethinking of Marxism and its blind spots, Dick Howard argues that the collapse of European communism in 1989 should not be identified with a victory for capitalism and makes possible a wholesale reevaluation of democratic politics in the U.S. and abroad. The author turns to the American and French Revolutions to uncover what was truly "revolutionary" about those events, arguing that two distinct styles of democratic life emerged, the implications of which were misinterpreted in light of the (...) rise of communism. Howard uses a critical rereading of Marx as a theorist of democracy to offer his audience a new way to think about this political ideal. He argues that it is democracy, rather than Marxism, that is radical and revolutionary, and that Marx could have seen this but did not. In Part I, Howard explores the attraction Marxism held for intellectuals, particularly French intellectuals, and he demonstrates how the critique of totalitarianism from a Marxist viewpoint allowed these intellectuals to see the radical nature of democracy. Part II examines two hundred years of democratic political life -- comparing America's experience as a democracy to that of France. Part III offers a rethinking of Marx's contribution to democratic politics. Howard concludes that Marx was attempting a "philosophy by other means," and that paradoxically, just because he was such an astute philosopher, Marx was unable to see the radical political implications of his own analyses. The philosophically justified "revolution" turns out to be the basis of an anti-politics whose end was foreshadowed by the fall of European communism in 1989. (shrink)

In any probabilistic theory, we say that a bipartite state ω on a composite system AB steers its marginal state ω B if, for any decomposition of ω B as a mixture ω B =∑ i p i β i of states β i on B, there exists an observable {a i } on A such that the conditional states $\omega_{B|a_{i}}$ are exactly the states β i . This is always so for pure bipartite states in quantum mechanics, a fact (...) first observed by Schrödinger in 1935. Here, we show that, for weakly self-dual state spaces (those isomorphic, but perhaps not canonically isomorphic, to their dual spaces), the assumption that every state of a system A is steered by some bipartite state of a composite AA consisting of two copies of A, amounts to the homogeneity of the state cone. If the state space is actually self-dual, and not just weakly so, this implies (via the Koecher-Vinberg Theorem) that it is the self-adjoint part of a formally real Jordan algebra, and hence, quite close to being quantum mechanical. (shrink)

This unpublished 1990 preprint argues that a crucial distinction in discussions of the many-worlds interpretation of quantum mechanics (MWI) is that between versions of the interpretation positing a physical multiplicity of worlds, and those in which the multiplicity is merely psychological, and due to the splitting of consciousness upon interaction with amplified quantum superpositions. It is argued that Everett's original version of the MWI belongs to the latter class, and that most of the criticisms leveled against the MWI, in particular (...) that it is illogical or incoherent, are not valid against such "psychological-multiplicity" versions. Attempts to derive the quantum-mechanical probabilities from the many-worlds interpretation are reviewed, and Everett's initial derivation is extended in an attempt to show that these are the unique possible probabilities. But there remains a challenge for proponents of the MWI: to show that their interpretation requires probabilities, rather than merely nonprobabilistic indeterminacy. A 2002 preface, revised in 2004, briefly discusses the extent to which I still agree with the claims in the paper. While its derivation of probabilities used, and failed to justify, noncontextuality, I still agree with the paper's general interpretation of the MWI, though not with the MWI itself. (shrink)