Rare copy number variants have a prominent role in the aetiology of schizophrenia and other neuropsychiatric disorders. Substantial risk for schizophrenia is conferred by large CNVs at several loci, including microdeletions at 1q21.1, 3q29, 15q13.3 and 22q11.2 and microduplication at 16p11.2. However, these CNVs collectively account for a small fraction of cases, and the relevant genes and neurobiological mechanisms are not well understood. Here we performed a large two-stage genome-wide scan of rare CNVs and report the significant association of copy (...) number gains at chromosome 7q36.3 with schizophrenia. Microduplications with variable breakpoints occurred within a 362-kilobase region and were detected in 29 of 8,290 patients versus 2 of 7,431 controls in the combined sample. All duplications overlapped or were located within 89 kilobases upstream of the vasoactive intestinal peptide receptor gene VIPR2. VIPR2 transcription and cyclic-AMP signalling were significantly increased in cultured lymphocytes from patients with microduplications of 7q36.3. These findings implicate altered vasoactive intestinal peptide signalling in the pathogenesis of schizophrenia and indicate the VPAC2 receptor as a potential target for the development of new antipsychotic drugs. © 2011 Macmillan Publishers Limited. All rights reserved. (shrink)

We report the identification of a recurrent, 520-kb 16p12.1 microdeletion associated with childhood developmental delay. The microdeletion was detected in 20 of 11,873 cases compared with 2 of 8,540 controls and replicated in a second series of 22 of 9,254 cases compared with 6 of 6,299 controls. Most deletions were inherited, with carrier parents likely to manifest neuropsychiatric phenotypes compared to non-carrier parents. Probands were more likely to carry an additional large copy-number variant when compared to matched controls. The clinical (...) features of individuals with two mutations were distinct from and/or more severe than those of individuals carrying only the co-occurring mutation. Our data support a two-hit model in which the 16p12.1 microdeletion both predisposes to neuropsychiatric phenotypes as a single event and exacerbates neurodevelopmental phenotypes in association with other large deletions or duplications. Analysis of other microdeletions with variable expressivity indicates that this two-hit model might be more generally applicable to neuropsychiatric disease. © 2010 Nature America, Inc. All rights reserved. (shrink)

Presents an analysis of Jonathan Edwards' theological position. This book includes a study of his life and the intellectual issues in the America of his time, and examines the problem of free will in connection with Leibniz, Locke, and Hume.

Prepared by editors of the distinguished series The Works of Jonathan Edwards, this authoritative anthology includes selected treatises, sermons, and autobiographical material by early America’s greatest theologian and philosopher.

Alan Millar's paper (2011) involves two parts, which I address in order, first taking up the issues concerning the goal of inquiry, and then the issues surrounding the appeal to reflective knowledge. I argue that the upshot of the considerations Millar raises count in favour of a more important role in value-driven epistemology for the notion of understanding and for the notion of epistemic justification, rather than for the notions of knowledge and reflective knowledge.

Every religion offers both hope and fear. They offer hope in virtue of the benefits promised to adherents, and fear in virtue of costs incurred by adversaries. In traditional Christianity, the costs incurred are expressed in terms of the doctrine of hell, according to which each person consigned to hell receives the same infinite punishment. This strong view of hell involves four distinct theses. First, it maintains that those in hell exist forever in that state (the Existence Thesis) and that (...) at least some human persons will end up in hell (the Anti-Universalism Thesis). Once in hell, there is no possibility of escape (the No Escape Thesis), and the justification of and purpose for hell is to mete out punishment to those whose earthly lives and character deserve it (the Retribution Thesis). (shrink)

v. 1. Freedom of the will -- v. 2. Religious affections -- v. 3. Original sin -- v. 4. The Great Awakening -- v. 5. Apocalyptic writings -- v. 6. Scientific and philosophical writings -- v. 7. The life of David Brainerd -- v. 8. Ethical writings -- v. 9. A history of the work of redemption -- v. 10. Sermons and discourses, 1720-1723 -- v. 13. The "miscellanies" (entry nos. a-z, aa-zz, 1-500) -- v. 15. Notes on Scripture -- (...) v. 17. Sermons and discourses, 1730-1733 -- v. 18. The "miscellanies" (entry nos. 501-832) -- v. 19. Sermons and discourses, 1734-1738 -- v. 20. The miscellanies -- v. 22. Sermons and discourses, 1739-1742 -- v. 24. The "blank Bible" (2 v.). (shrink)

In the World Library of Psychologists series, international experts themselves present career-long collections of what they judge to be their finest pieces - extracts from books, key articles, salient research findings, and their major theoretical and practical contributions. Jonathan St B T Evans is amongst the foremost cognitive psychologists of his generation, having been influential in spearheading developments in the psychological study of reasoning from its very beginnings in the 1970s up to the present day. This volume of self-selected (...) papers recognises Professor Evan's major contribution to the psychological study of thinking and reasoning by bringing together his most influential and important works. Early selections in the book focus upon experimental studies of reasoning - matching bias in the Wason selection task, belief bias in syllogistic reasoning, and also seminal work on the understanding of conditional statements. The later selections include Evans' work on more general forms of dual process and dual system theory, and his recent account of two minds in one brain. The volume also contains chapters which highlight Evans' contribution to the topic of human rationality, and also his influence on the development of the "new paradigm" in the psychology of reasoning. The key developments in the psychology of reasoning are paralleled by those in Evans's own intellectual history, and the book will therefore make essential reading for all researchers in the psychology of reasoning, and a wider audience of graduate and upper-level undergraduate students with an interest in reasoning and/or dual process theory. (shrink)

The human right to health has been established in international law since 1976. However, philosophers have often regarded human rights doctrine as a marginal contribution to political philosophy, or have attempted to distinguish ‘human rights proper’ from ‘aspirations’, with the human right to health often considered as falling into the latter category. Here the human right to health is defended as an attractive approach to global health, and responses are offered to a series of criticisms concerning its demandingness.

Originally published posthumously in 1955, Harvey G. Townsend's Philosophy of Jonathan Edwards reprinted some of Edwards' most important early compositions on natural philosophy, Of Being and The Mind, and collected nearly two hundred Miscellanies entries, some of them published here for the first time. In his introduction, Townsend points to Edwards' radical idealism that derived from Christian Platonism and John Locke rather than George Berkeley, as commonly thought. Townsend's work represents an important sourcebook for Edwards' writings, and his introduction (...) presents a clear picture of mainstream Edwards scholarship at the middle of the twentieth century. (shrink)

I should like to convey to you some doubts which have occurred to me on the subject of the notion of consciousness that prevails in all our treatises on psychology.

The dominant approach to environmental policy endorsed by conservative and libertarian policy thinkers, so-called “free market environmentalism”, is grounded in the recognition and protection of property rights in environmental resources. Despite this normative commitment to property rights, most self-described FME advocates adopt a utilitarian, welfare-maximization approach to climate change policy, arguing that the costs of mitigation measures could outweigh the costs of climate change itself. Yet even if anthropogenic climate change is decidedly less than catastrophic, human-induced climate change is likely (...) to contribute to environmental changes that violate traditional conceptions of property rights. Viewed globally, the actions of some countries—primarily industrialized nations—are likely to increase environmental harms suffered by other countries—less developed nations that have not made any significant contribution to climate change. It may well be that aggregate human welfare would be maximized in a warmer, wealthier world, or that the gains from climate change will offset environmental losses. Yet such claims, even if demonstrated, would not address the normative concern that the consequences of anthropogenic global warming would infringe upon the rights of people in less-developed nations. As a consequence, this paper calls for a rethinking of FME approaches to climate change policy. (shrink)

I came to epistemology through an interest in the concept of rationality, and especially through the attacks on the rationality of religious believers. My thoughts at the time focused on the disappointing quality of the arguments for and against religious belief, and I recall being astonished at the time that philosophers capable of such penetrating insight in other areas had nothing that seemed either penetrating or original. The defenders sounded too much like mere apologists for the faith, and the attackers (...) arid and dull, with both sides often exuding a scent of intellectual dishonesty. (shrink)

Jonathan Dancy works within almost all fields of philosophy but is best known as the leading proponent of moral particularism. Particularism challenges “traditional” moral theories, such as Contractualism, Kantianism and Utilitarianism, in that it denies that moral thought and judgement relies upon, or is made possible by, a set of more or less well-defined, hierarchical principles. During the summer of 2006, the Philosophy Departments of Lund University (Sweden) and the University of Reading (England) began a series of exchanges to (...) take place every other year, alternating between the departments. Andreas Lind and Johan Brännmark arranged to meet Dancy during the first meeting in Lund to talk about questions regarding particularism, moral theory and the shape of the analytical tradition. The major part of the conversation is printed below. (shrink)

COMPARING LAW COMPARING RELIGION -- THE SCIENTIFIC STUDY OF RELIGION AND ITS CULTURED DESPISERS -- INTRODUCING RELIGION -- Index of Authors.

Morality exercises a deep and questionable influence on the way we live our lives. The influence is deep both because moral injunctions are embedded in our psyches long before we can reflect on their status and because even after we become reflective agents, the question of how we should live our lives among others is intimately bound up with the more general question of how we should live our lives: our stance toward morality and our conception of our lives as (...) having significance are of a piece. The influence is questionable because morality pretends to a level of objectivity that it may not possess. Moral injunctions are meant to be binding on us in some way that is independent of the desires or preferences we may happen to have. When one asserts that a certain action is morally worthy or shameful one is, prime facie, doing more than merely expressing approval or disapproval or trying to get others to act as instruments of one's own will. If moral assertions were shown, at bottom, to be merely such exhortations, then they would be shown to wear a disguise. Morality would be revealed as pretending to an objectivity it does not have, and such a revelation could not but have a profound impact on our lives. It is doubtful that such a revelation could be kept locked up inside our studies. (shrink)

Arrhenius and Rabinowicz have argued that Millian qualitative superiorities are possible without assuming that any pleasure, or type of pleasure, is infinitely superior to another. But AR's analysis is fatally flawed in the context of ethical hedonism, where the assumption in question is necessary and sufficient for Millian qualitative superiorities. Marginalist analysis of the sort pressed by AR continues to have a valid role to play within any plausible version of hedonism, provided the fundamental incoherence that infects AR's use of (...) such analysis is removed. But what AR call ‘Millian superiorities’ are never genuine qualitative superiorities in Mill's sense. Mill scholars need to appreciate this point and recognize that the interpretation of qualitative superiorities as infinite superiorities is the only interpretation which is compatible with the text of Mill's Utilitarianism. The continuing failure to appreciate the possibility of infinite superiorities has precluded any adequate understanding of the extraordinary structure of Mill's pluralistic hedonistic utilitarianism. (shrink)

John Stuart Mill argued, in his Principles of Political Economy, that existing laws and customs of private property ought to be reformed to promote a far more egalitarian form of capitalism than hitherto observed anywhere. He went on to suggest that such an ideal capitalism might evolve spontaneously into a decentralized socialism involving a market system of competing worker co-operatives. That possibility of market socialism emerged only as the working classes gradually developed the intellectual and moral qualities required for worker (...) co-operatives to succeed against private firms. Workers would tend to reject the hierarchical wage relation as they developed the requisite personal qualities, he believed, and capitalists, facing escalating wages for skilled labour as a result of the diminishing supply of high-quality workers for hire, would tend to lend their capital to the worker co-operatives ‘at a diminishing rate of interest, and at last, perhaps, even to exchange their capital for terminable annuities. In this or some such mode’, he speculated, ‘the existing accumulations of capital might honestly, and by a kind of spontaneous process, become in the end the joint property of all who participate in their productive employment: a transformation which, thus effected, would be the nearest approach to social justice, and the most beneficial ordering of industrial affairs for the universal good, which it is possible at present to foresee.’. (shrink)

In Direct Belief I argue for the Theory of Direct Belief, which treats having a belief about an individual as an unmediated relation between the believer and the individual the belief is about. After a critical review of alternative positions, I use Grice’s theory of conversational implicature to provide a detailed pragmatic account of substitution failure in belief ascriptions and go on to defend this view against objections, including those based on an unwarranted “Inner Speech” Picture of Thought. The work (...) serves as a case study in pragmatic explanation, dealing also with methodological issues about context-sensitivity in language and the relation between semantics and pragmatics. (shrink)

I continue my argument that Millian qualitative superiorities are infinite superiorities: one pleasant feeling, or type of pleasant feeling, is qualitatively superior to another in Mill's sense if and only if even a bit of the superior is more pleasant than any finite quantity of the inferior, however large. This gives rise to a hierarchy of higher and lower pleasures such that a reasonable hedonist always refuses to sacrifice a higher for a lower irrespective of the finite amounts of each. (...) Some indication of why this absolute refusal may be reasonable is provided in the course of outlining the content of the Millian hierarchy. It emerges that Mill's hedonistic utilitarianism has an extraordinary structure because it gives absolute priority over competing considerations to a code of justice that distributes equal rights and correlative duties for all. His utilitarianism also recognizes that certain aesthetic and spiritual pleasures may be qualitatively superior even to the pleasant feeling of security associated with the moral sentiment of justice. Thus, for instance, a noble individual may reasonably choose to waive his own rights so as to perform beautiful supererogatory actions that provide great benefits for others at the sacrifice of the right-holder's own vital interests. (shrink)

The Oxford Translation of Aristotle was originally published in 12 volumes between 1912 and 1954. It is universally recognized as the standard English version of Aristotle. This revised edition contains the substance of the original Translation, slightly emended in light of recent scholarship three of the original versions have been replaced by new translations and a new and enlarged selection of Fragments has been added. The aim of the translation remains the same: to make the surviving works of Aristotle readily (...) accessible to English speaking readers. (shrink)

The law tends to think that there is no difficulty about identifying humans. When someone is born, her name is entered into a statutory register. She is ‘X’ in the eyes of the law. At some point, ‘X’ will die and her name will be recorded in another register. If anyone suggested that the second X was not the same as the first, the suggestion would be met with bewilderment. During X's lifetime, the civil law assumed that the X who (...) entered into a contract was the same person who breached it. The criminal law assumed that X, at the age of 80, was liable for criminal offences ‘she’ committed at the age of 18. This accords with the way we talk. ‘She's not herself today’, we say; or ‘When he killed his wife he wasn't in his right mind’. The intuition has high authority: ‘To thine own self be true’, urged Polonius.1 It sounds as if we believe in souls—immutable, core essences that constitute our real selves. Medicine conspires in the belief. If you become mentally ill, a psychiatrist will seek to get you back to your right mind. The Mental Capacity Act 1985 states that when a patient loses capacity the only lawful interventions will be interventions which are in that patient's best interests,2 and that in determining what those interests are the decision-maker must have …. (shrink)