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)

Circadian rhythm abnormalities in bipolar disorder have led to a search for genetic abnormalities in circadian "clock genes" associated with BD. However, no significant clock gene findings have emerged from genome-wide association studies. At least three factors could account for this discrepancy: complex traits are polygenic, the organization of the clock is more complex than previously recognized, and/or genetic risk for BD may be shared across multiple illnesses. To investigate these issues, we considered the clock gene network at three levels: (...) essential "core" clock genes, upstream circadian clock modulators, and downstream clock controlled genes. Using relaxed thresholds for GWAS statistical significance, we determined the rates of clock vs. control genetic associations with BD, and four additional illnesses that share clinical features and/or genetic risk with BD. Then we compared the results to a set of lithium-responsive genes. Associations with BD-spectrum illnesses and lithium-responsiveness were both enriched among core clock genes but not among upstream clock modulators. Associations with BD-spectrum illnesses and lithium-responsiveness were also enriched among pervasively rhythmic clock-controlled genes but not among genes that were less pervasively rhythmic or non-rhythmic. Our analysis reveals previously unrecognized associations between clock genes and BD-spectrum illnesses, partly reconciling previously discordant results from past GWAS and candidate gene studies. (shrink)

This book is a defense of modal realism; the thesis that our world is but one of a plurality of worlds, and that the individuals that inhabit our world are only a few out of all the inhabitants of all the worlds. Lewis argues that the philosophical utility of modal realism is a good reason for believing that it is true.

In lieu of an abstract, here is a brief excerpt of the content:Louis Agassiz and the Platonist Story of Creation at Harvard, 1795-1846David K. NartonisIn 1846, naturalist Louis Agassiz took Harvard College by storm with his idealist approach to nature. In his initial lectures, repeated in New York the following year, Agassiz announced, "We have that within ourselves which assures us of participation in the Divine Nature and it is a particular characteristic of man to be able to rise in (...) that way above material Nature, and to understand intellectual existences." He then made it clear that by intellectual existences he meant a divine plan of creation. "What naturalists intend when they speak of what they call 'types'... may be easily understood by comparison. We all know that architects construct our dwellings according to plans conceived by them before the erection of the edifice."1 There is no doubt that Agassiz valued the careful collection of observational data. "It has only been step by step that man has acquired an insight into this plan."2 But his empiricism, if that is the right term, was entirely subordinate to apprehension of divine ideas, which alone deserved to be called science. In one recent account, The Metaphysical Club, which contains an excellent discussion of Agassiz's American career, author Louis Menand accurately describes this dual emphasis on observation and intuition. But Menand leaves unstated the problem of [End Page 437] Agassiz's welcome at Harvard, attributing his instant popularity to force of character.3A fuller explanation of Agassiz's welcome is to be found in the Scottish textbooks that dominated the Harvard philosophy curriculum prior to his arrival.4 Like Agassiz, textbook authors Thomas Reid, Dugald Stewart, and Thomas Brown recognized observation and intuition as twin sources of human knowledge. According to them, we observe our own moral tendencies and interpret them in the light of intuited ethical principles that even God must obey. Similarly, we observe nature and interpret its workings with the aid of intuited principles of common sense.5 There is no doubt that this dual emphasis on observation and intuition was entirely consistent with Agassiz's idealist biology. But his definition of species and genera as intellectual existences in the divine mind was not to be found in the official Scottish texts. In fact, Dugald Stewart, who governed the philosophy curriculum after 1820, insisted that there are "no existences in nature corresponding to general terms, and the objects of our attention in all our general speculations are not ideas but words."6 This was "long misunderstood by philosophers, who imagined that a generic word expresses an actual existence distinct from the individuals of which the genus is composed."7 Similarly, Thomas Brown lamented, "One fundamental error... as long as it retained its hold of the understanding, must have rendered all its energies ineffectual, by wasting them in search of objects, which had no real existence... I allude to... the various orders of universals."8 In this one respect, Stewart and Brown were in agreement with Alexander Pope when he counseled his many American readers "presume not God to scan" and ridiculed those who would "soar with Plato to th' empyreal sphere."9But Harvard students and faculty were also reading books that promoted the intellectual existences that Agassiz saw behind nature and the Scots did [End Page 438] not. Chief among these books were Plato's Works (ca. 360 BCE), Philo's De Opificio Mundi (20 BCE to 50 CE), Ralph Cudworth's The True Intellectual System of the World (1678), and John Norris's An Essay towards the Theory of the Ideal or Intellectual World (1701–04). These combined with such widely popular literature as John Milton's Paradise Lost (1668) and the prose works of Samuel Coleridge to form a kind of unofficial curriculum that ultimately made Agassiz's idealist view of nature especially welcome at Harvard.10 Modest at first, Harvard interest in intellectual existences bloomed with the appearance of books by Romantic writers on campus. In order to illustrate this long development, I will bolster my explanation with data from Harvard College library borrowing records—handwritten lists of the books borrowed by each library user during a one- or two-year period... (shrink)

Counterfactuals is David Lewis' forceful presentation of and sustained argument for a particular view about propositions which express contrary to fact conditionals, including his famous defense of realism about possible worlds and his theory of laws of nature.

This monograph examines the past, present, and potential relationship between American pragmatism and communication research. The contributors provide a bridge between communication studies and philosophy, subjects often developed somewhat in isolation from each other. Addressing topics, such as qualitative and quantitative research, ethics, media research, and feminist studies, the chapters in this volume: *discuss how a pragmatic, Darwinian approach to inquiry has guided and might further guide communication research; *advocate a functional view of communication, based on Dewey's mature notion of (...) transaction; *articulate a pragmatist's aesthetics and connect it to Deweyan democracy; *discuss the similarities and differences between Dewey's notion of inquiry and the philosophical hermeneutics of Hans-Georg Gadamer; *apply accommodation theory, linked to symbolic interactionism and more generally to the social behaviorism of George H. Mead and his followers, to media research; *interpret media-effects evidence in light of pragmatist ideas about inquiry; and *argue that pragmatism theorizes about despair and life's sense of the tragic. This book is written to be readily accessible to students and professional academics within and outside the field of communication studies without extensive training in specialized areas of communication study. (shrink)

Second part of the translation into Spanish of David Lewis' "New Work for a Theory of Universals", corresponding to the last sections of the original paper. || Segunda parte de la traducción al español del trabajo de David Lewis "New Work for a Theory of Universals", correspondiente a últimas secciones del artículo original. Artículo original publicado en: Australasian Journal of Philosophy, Vol. 61, No. 4, Dec. 1983, pp. 343-377.

Topics in Cognitive Science, Volume 13, Issue 1, Page 128-141, January 2021.

It is advisable to treat some sorts of discourse about fiction with the aid of an intensional operator "in such-And-Such fiction...." the operator may appear either explicitly or tacitly. It may be analyzed in terms of similarity of worlds, As follows: "in the fiction f, A" means that a is true in those of the worlds where f is told as known fact rather than fiction that differ least from our world, Or from the belief worlds of the community in (...) which the fiction originated. (shrink)

The aim of the paper is to show that there are actions which are non-intentional. An account is first given which links intentional and unintentional action to acting for a reason, or appropriate causation by an intention. Mannerisms and habitual actions are then presented as examples of behavior which are actions, but which are not done in the course of acting for a reason. This account has advantages over that of Hursthouse's "arational actions," which are allegedly intentional actions done for (...) no reason at all. Finally, one consequence of neglecting non-intentional action is discussed to illustrate its importance. (shrink)

What knowledge would suffice to yield an interpretation of an arbitrary utterance of a language when such knowledge is based on evidence plausibly available to a nonspeaker of that language? it is argued that it is enough to know a theory of truth for the language and that the theory satisfies tarski's 'convention t' and that it gives an optimal fit to data about sentences held true, Under specified conditions, By native speakers.

D. H. Hodgson has argued that among highly knowledgeable and rational act-Utilitarians there is no non-Circular reason to be truthful or to expect truthfulness from others; wherefore these utilitarians forfeit the benefits of communication. I reply that hodgson goes wrong by tacitly assuming that his utilitarians have no premises to reason from except those that hodgson lays down in specifying the example under consideration.

Are today’s wars different from earlier wars? Or do we need a different ethics for old and new wars alike? Unlike most books on the morality of war, this book rejects the ‘just war’ tradition, proposing a virtue ethics of war to take its place. Like torture, war cannot be justified. This book asks and answers the question: “If war is a very great evil, would a leader with courage, justice, compassion, and all the other moral virtues ever choose to (...) fight a war?” A ‘philosophy of co-existence’ is proposed which is much more restrictive than just war theory but not pacifist. War can be correctly chosen by a virtuous leader only in rare ‘supreme emergencies’ when faced with enemies as evil as Hitler. This virtue ethics approach to war is used to find new answers to difficult issues such as humanitarian intervention, terrorism and weapons of mass destruction. (shrink)

If a guilty offender is justly sentenced to be punished and an innocent volunteer agrees to be punished instead, is that any reason to leave the offender unpunished? In the context of mundane criminal justice, we mostly think not. But in a religious context, some Christians do believe in penal substitution as a theory of the atonement. However, it is not just these Christians, but most of us, who are of two minds. If the punishment is an imprisonment or death, (...) we do not believe in penal substitution. But if it’s a fine, even a big fine, we mostly do. (shrink)

An extrinsic desire is defined as a desire for something, not for its own sake, but for its supposed propensity to secure something else that one desires. I argue that the notion of ‘extrinsic desire’ is theoretically redundant. I begin by defining desire as a propositional attitude with a desirability characterization. The roles of desire and intention in practical reasoning are distinguished. I show that extrinsic desire does not have its own motivational role. I also show that extrinsic desire is (...) not needed for other roles besides motivation to carry out the means, and is not generated by reason. Finally, I argue that an account of extrinsic motivation in terms of intention is preferable to an account in terms of extrinsic desire. Because of the fundamental differences between extrinsic desire and intrinsic desire, it is more advantageous to distinguish between them as different kinds of mental states: intention and desire. (shrink)

The void is deadly. If you were cast into a void, it would cause you to die in just a few minutes. It would suck the air from your lungs. It would boil your blood. It would drain the warmth from your body. And it would inflate enclosures in your body until they burst}.

A solution to the problem of intrinsic change for enduring things should meet three conditions. It should not replace monadic intrinsic properties by relations. It should not replace the having simpliciter of properties by standing in some relation to them. It should not rely on an unexplained notion of having an intrinsic property at a time. Johnston's solution satisfies the first condition at the expense of the second. Haslanger's solution satisfies the first and second at the expense of the third.

In his note "can there be vague objects?" ("analysis", 1978), Gareth evans presents a purported proof that there can be no vague identity statements. Some readers think that evans endorses the proof and its false conclusion. Not so. His point is that those who put vagueness in the world, Rather than in language, Will have no way to fault the proof and no way to escape the false conclusion.

I argue that the moral distinction in double effect cases rests on a difference not in intention as traditionally stated in the Doctrine of Double Effect (DDE), but in desire. The traditional DDE has difficulty ensuring that an agent intends the bad effect just in those cases where what he does is morally objectionable. I show firstly that the mental state of a rational agent who is certain that a side-effect will occur satisfies Bratman's criteria for intending that effect. I (...) then clarify the nature of the moral distinction in double effect cases and how it can be used to evaluate the moral blameworthiness of agents rather than the moral status of acts. The agent's blameworthiness is reduced not by his lack of intention but by his desire not to bring about the side-effect, and the 'counterfactual test' can be used to determine whether he desires the effect in acting. In my version, the DDE has its rationale in virtue ethics; it is not liable to abuse as the traditional version is; and it makes more plausible distinctions when applied to standard examples. (shrink)

is the second-order theory of the part-whole relation. It can express such hypotheses about the size of Reality as that there are inaccessibly many atoms. Take a non-empty class to have exactly its non-empty subclasses as parts; hence, its singleton subclasses as atomic parts. Then standard set theory becomes the theory of the member-singleton function—better, the theory of all singleton functions—within the framework of megethology. Given inaccessibly many atoms and a specification of which atoms are urelements, a singleton function exists, (...) unique up to isomorphism. (This article is partly abridged from my Parts of Classes, partly a sequel.). (shrink)

As the interest in the quality of work life grows, it becomes increasingly apparent that certain practices within this arena require critical scrutiny. This paper is an examination of one such area, performance appraisal (PA). We examine some of the main conceptual issues in PA, and we sketch some key, practical dilemmas that may arise in the use of PA. We conclude that one can morally justify the use of PA under certain condition, and we suggest possible solutions to key (...) ethical dilemmas that are faced by the manager and the employee. (shrink)

This is the second volume of philosophical essays by one of the most innovative and influential philosophers now writing in English. Containing thirteen papers in all, the book includes both new essays and previously published papers, some of them with extensive new postscripts reflecting Lewis's current thinking. The papers in Volume II focus on causation and several other closely related topics, including counterfactual and indicative conditionals, the direction of time, subjective and objective probability, causation, explanation, perception, free will, and rational (...) decision. Throughout, Lewis analyzes global features of the world in such a way as to show that they might turn out to supervene on the spatiotemporal arrangement of local qualities. (shrink)

My paper critiques the comparability requirement that practical reason is limited by the possibility of comparing alternatives. I describe methods of reasoning that are compatible with choice between incomparable options, and discuss a mistake about intention that supports the view that comparing alternatives is the only way to choose rationally. I then explain how a model of rational choice that prescribes the comparison of alternatives invents unacceptable concepts to make comparability possible. Finally, I criticize the assumption of the unity of (...) practical reason that requires that prudential and moral choices are both made by comparing alternatives. It turns out that moral conflicts that are intractable for those who reason with a method of comparison may be resolvable by using moral reasoning that does not involve the comparison of alternatives in terms of a comprehensive value. Making room for such forms of reasoning is preferable to denying incomparability. (shrink)