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)

Greenberg restructures the history of modern Jewish thought comprehensively, providing first-time English translations of Reggio, Krokhmal, Maimon, Samuel Hirsch, Formstecher, Steinheim, Ascher, Einhorn, Samuel David Luzzatto, and Hermann Cohen. The availability of these sources fills a gap in the field and stimulates new directions for teaching and scholarly research in modern Jewish thought.

In this book, which thoroughly revises and greatly expands his classic work Sameness and Substance, David Wiggins retrieves and refurbishes in the light of twentieth-century logic and logical theory certain conceptions of identity, of substance and of persistence through change that philosophy inherits from its past. In this new version, he vindicates the absoluteness, necessity, determinateness and all or nothing character of identity against rival conceptions. He defends a form of essentialism that he calls individuative essentialism, and then a (...) form of realism that he calls conceptualist realism. In a final chapter he advocates a human being-based conception of the identity and individuation of persons, arguing that any satisfactory account of personal memory must make reference to the life of the rememberer himself. This important book will appeal to a wide range of readers in metaphysics, philosophical logic, and analytic philosophy. (shrink)

Lipsey and Lancaster's "general theory of second best" is widely thought to have significant implications for applied theorizing about the institutions and policies that most effectively implement abstract normative principles. It is also widely thought to have little significance for theorizing about which abstract normative principles we ought to implement. Contrary to this conventional wisdom, I show how the second-best theorem can be extended to myriad domains beyond applied normative theorizing, and in particular to more abstract theorizing about the normative (...) principles we should aim to implement. I start by separating the mathematical model used to prove the second-best theorem from its familiar economic interpretation. I then develop an alternative normative-theoretic interpretation of the model, which yields a novel second best theorem for idealistic normative theory. My method for developing this interpretation provides a template for developing additional interpretations that can extend the reach of the second-best theorem beyond normative theoretical domains. I also show how, within any domain, the implications of the second-best theorem are more specific than is typically thought. I conclude with some brief remarks on the value of mathematical models for conceptual exploration. (shrink)

Artificial intelligence has historically been conceptualized in anthropomorphic terms. Some algorithms deploy biomimetic designs in a deliberate attempt to effect a sort of digital isomorphism of the human brain. Others leverage more general learning strategies that happen to coincide with popular theories of cognitive science and social epistemology. In this paper, I challenge the anthropomorphic credentials of the neural network algorithm, whose similarities to human cognition I argue are vastly overstated and narrowly construed. I submit that three alternative supervised learning (...) methods—namely lasso penalties, bagging, and boosting—offer subtler, more interesting analogies to human reasoning as both an individual and a social phenomenon. Despite the temptation to fall back on anthropomorphic tropes when discussing AI, however, I conclude that such rhetoric is at best misleading and at worst downright dangerous. The impulse to humanize algorithms is an obstacle to properly conceptualizing the ethical challenges posed by emerging technologies. (shrink)

A collection of 14 essays honoring the life and work of Oxford philosopher Wiggins touching on topics from ancient philosophy to ethics, metaphysics and the theory of meaning. The contributing scholars debate many of the seminal issues of Wiggins' work, including the determinancy of distinctness, relative identity, naturalism in ethics, logic and truth in moral judgments, and the practical wisdom of Aristotle. The collection uniquely features replies by Wiggins to each of the papers. Annotation copyright by Book News, Inc., Portland, (...) OR. (shrink)

Why study notations, diagrams, or more broadly the variety of nonverbal “representations” or “signs” that are used in mathematical practice? This chapter maps out recent work on the topic by distinguishing three main philosophical motivations for doing so. First, some work (like that on diagrammatic reasoning) studies signs to recover norms of informal or historical mathematical practices that would get lost if the particular signs that these practices rely on were translated away; work in this vein has the potential to (...) broaden our view of the specific normativity of mathematics beyond logical proof. Second, some work focuses on signs to highlight the open-ended and “nonrigorous” aspects of mathematical practice, and the role of these aspects in the historical development of mathematics. The third motivation is based on the following observation: the reason differences in signs matter in mathematics is that humans are finite agents, with cognitive and computational limitations. Accordingly, studying signs can be a way to study how human computational constraints shape the mathematics that we do, and to tackle the topic of mathematical understanding. (shrink)

The cinematic Other is interpreted as an unconscious personality, a denied part of the protagonist that appears in his life as a shadowy menace who won't go away. Overall the book aims to show how movies envision the unconscious Other we all too often project on other people.

The cinematic Other is interpreted as an unconscious personality, a denied part of the protagonist that appears in his life as a shadowy menace who won't go away. Overall the book aims to show how movies envision the unconscious Other we all too often project on other people.

According to dispositionalism about modality, a proposition <p> is possible just in case something has, or some things have, a power or disposition for its truth; and <p> is necessary just in case nothing has a power for its falsity. But are there enough powers to go around? In Yates (2015) I argued that in the case of mathematical truths such as <2+2=4>, nothing has the power to bring about their falsity or their truth, which means they come out both (...) necessary and not possible. Combining this with axiom (T), it is easy to derive a contradiction. I suggested that dispositionalists ought to retreat a little and say that <p> is possible just in case either p, or there is a power to bring it about that p, grounding the possibility of mathematical propositions in their truth rather than in powers. Vetter’s (2015) has the resources to provide a response to my argument, and in her (2018) she explicitly addresses it by arguing for a plenitude of powers, based on the idea that dispositions come in degrees, with necessary properties a limiting case of dispositionality. On this view there is a power for <2+2=4>, without there being a power to bring about its truth. In this paper I argue that Vetter’s case for plenitude does not work. However, I suggest, if we are prepared to accept metaphysical causation, a case can be made that there is indeed a power for <2+2=4>. (shrink)

We propose a formal framework for interpretable machine learning. Combining elements from statistical learning, causal interventionism, and decision theory, we design an idealised explanation game in which players collaborate to find the best explanation for a given algorithmic prediction. Through an iterative procedure of questions and answers, the players establish a three-dimensional Pareto frontier that describes the optimal trade-offs between explanatory accuracy, simplicity, and relevance. Multiple rounds are played at different levels of abstraction, allowing the players to explore overlapping causal (...) patterns of variable granularity and scope. We characterise the conditions under which such a game is almost surely guaranteed to converge on a optimal explanation surface in polynomial time, and highlight obstacles that will tend to prevent the players from advancing beyond certain explanatory thresholds. The game serves a descriptive and a normative function, establishing a conceptual space in which to analyse and compare existing proposals, as well as design new and improved solutions. (shrink)

While there are many legal textbooks on the laws of armed conflict and academic works on ethical issues in international relations, this is the first text on the relevance of legal and normative issues in military practice. It covers the entire spectrum of military operations and is written with military deicision-makers particularly in mind.

Extant theoretical work on the political resource curse implies that dependence on resource revenues should decrease autocracies’ likelihood of democratizing but not necessarily affect democracies’ chances of survival. Yet most previous empirical studies estimate models that are ill-suited to address this claim. We improve upon earlier studies, estimating a dynamic logit model that interacts a continuous measure of resource dependence with an indicator of regime type using data from 166 countries, covering the period from 1816-2006. We find that an increase (...) in resource dependence at time t - 1 increases the likelihood of autocratic persistence at t, but has no appreciable effect on democratic survival. We go beyond existing empirical studies to show that increases in resource dependence have persistent and substantial cumulative effects on autocracies' likelihood of becoming democratic over the long-term, showing that the total effect of resource dependence on regime type is much larger than the short-term (one period) effect indicates. (shrink)

Japan and the Enemies of Open Political Science argues that Eurocentric blindness is a scientific failing, not a moral one. In a way true of no other political system, Japan's greatness has the potential to enliven and reform almost all the main branches of Western Political Science. David Williams criticizes Western social science, Anglo-American Philosophy and French Theory and explains why mainstream economists, historians of political thought and postculturalists have ignored Japan's modern achievements. Williams demonstrates why the renewal of (...) social science and the nurturing of a "a philosophy of the Pacific Century" requires a sustained act of intellectual demolition. (shrink)

This is an in-depth study of J.G. Fichte’s philosophy of mathematics and theory of geometry. It investigates both the external formal and internal cognitive parallels between the axioms, intuitions and constructions of geometry and the scientific methodology of the Fichtean system of philosophy. In contrast to “ordinary” Euclidean geometry, in his Erlanger Logik of 1805 Fichte posits a model of an “ursprüngliche” or original geometry – that is to say, a synthetic and constructivistic conception grounded in ideal archetypal elements that (...) are grasped through geometrical or intelligible intuition. -/- Accordingly, this study classifies Fichte’s philosophy of mathematics as a whole as a species of mathematical Platonism or neo-Platonism, and concludes that the Wissenschaftslehre itself may be read as an attempt at a new philosophical mathesis, or “mathesis of the mind.” -/- “This work testifies to the author's exact and extensive knowledge of the Fichtean texts, as well as of the philosophical, scientific and historical contexts. Wood has opened up completely new paths for Fichte research, and examines with clarity and precision a domain that up to now has hardly been researched.” Professor Dr. Marco Ivaldo -/- “This study, written in a language distinguished by its limpidity and precision, and constantly supported by a close reading of the Fichtean texts and secondary literature, furnishes highly detailed and convincing demonstrations. In directly confronting the difficult historical relationship between the Wissenschaftslehre and mathematics, the author has broken new ground that is at once stimulating, decidedly innovative, and elegantly audacious.” Professor Dr. Emmanuel Cattin. (shrink)

In 1962, the philosopher Richard Taylor used six commonly accepted presuppositions to imply that human beings have no control over the future. David Foster Wallace not only took issue with Taylor's method, which, according to him, scrambled the relations of logic, language, and the physical world, but also noted a semantic trick at the heart of Taylor's argument. _Fate, Time, and Language_ presents Wallace's brilliant critique of Taylor's work. Written long before the publication of his fiction and essays, Wallace's (...) thesis reveals his great skepticism of abstract thinking made to function as a negation of something more genuine and real. He was especially suspicious of certain paradigms of thought-the cerebral aestheticism of modernism, the clever gimmickry of postmodernism-that abandoned "the very old traditional human verities that have to do with spirituality and emotion and community." As Wallace rises to meet the challenge to free will presented by Taylor, we witness the developing perspective of this major novelist, along with his struggle to establish solid logical ground for his convictions. This volume, edited by Steven M. Cahn and Maureen Eckert, reproduces Taylor's original article and other works on fatalism cited by Wallace. James Ryerson's introduction connects Wallace's early philosophical work to the themes and explorations of his later fiction, and Jay Garfield supplies a critical biographical epilogue. (shrink)

The author of this book has traced the major lines of argument over those years in a most engaging style with clear descriptions of the concepts and ideas.

David Williams explores the complex links between Condorcet as visionary ideologist and pragmatic legislator, and between his concept of modernity and the management of change. The Marquis de Condorcet was one of the few Enlightenment thinkers to witness and participate in the French Revolution. Based on an extensive array of printed and original manuscript sources, Williams' analysis of Condorcet's politics will be a major contribution to Enlightenment studies.

The Discovery of Evolution explains what the theory of evolution is all about by providing a historical narrative of discovery. Some of the major puzzles that confront anyone studying living things are discussed and it details how these were solved from an evolutionary perspective. Beginning with the emergence of the early naturalists in the seventeenth century, the scientific discoveries that led up to and then flowed from Darwin and Wallace's theory of evolution by natural selection are then discussed, and finally (...) the modern evolutionary studies at the close of the twentieth century are detailed. This new edition of The Discovery of Evolution is fully updated and contains a new chapter on the evolutionary studies of the twentieth century. By approaching the topic of evolution in this way, it is made accessible to the non-specialist and no previous study of biology is required in order to read and understand this book. (shrink)

Interpretation -- Introduction -- Interpreting Plato -- The political culture of Plato's early dialogues -- Dialogue -- Character and history -- The mouthpiece principle -- Forms of evidence -- Desire -- Socrates and eros -- The subjectivist conception of desire -- Instrumental and terminal desire -- Rational and irrational desires -- Desire in the critique of Akrasia -- Interpreting Lysis -- The deficiency conception of desire -- Inauthentic friendship -- Platonic desire -- Antiphilosophical desires -- Knowledge -- Excellence as wisdom (...) -- The epistemic unity of excellence -- Dunamis and technê -- Goodness and form -- The epistemological priority of definitional knowledge -- Ordinary ethical knowledge -- Method -- The Socratic fallacy -- Socrates' pursuit of definitions -- Hupothesis -- Two postulates -- The geometrical illustration -- Geometrical analysis -- The method of reasoning from a postulate -- Elenchus and hupothesis -- Knowledge and aitia -- F-conditions -- Cognitive security -- Aporia -- Forms of aporia -- Dramatic aporia -- The example of Charmides -- Charmides as autobiography -- The politics of Sôphrosunê -- Critias' Philotimia -- Self-knowledge and the knowledge of knowledge -- Knowledge of knowledge and knowledge of the good -- Philosophy and the polis. (shrink)

There have been serious controversies in the latter part of the 20th century about the roles and functions of scientific and medical research. In whose interests are medical and biomedical experiments conducted and what are the ethical implications of experimentation on subjects unable to give competent consent? From the decades following the Second World War and calls for the global banning of medical research to the cautious return to the notion that in controlled circumstances, medical research on human subjects is (...) in the best interest of the given individual and the broader population, this book addresses the key implications of experimentation on humans. This volume covers major ethical themes within biomedical research providing historical, philosophical, legal and policy reflections on the literature and specific issues in the field of research on human subjects. Focusing on special populations (the elderly, children, prisoners and the cognitively impaired) it represents the most up-to-date review of the special ethical and legal conflicts that arise with relation to experimentation on subjects from these groups. In the light of current initiatives for law reform pertaining to research ethics the world over, this volume provides a timely, comprehensive and provocative exploration of the field. The volume has been carefully organized to present important philosophical perspectives on organizing principles that should underlie any practical application. A forward-looking historical review of the regulatory regimes of principal jurisdictions, including of the legal controls already in place, provides the backdrop for future policy initiatives. Additionally, in the light of global restructuring of health care systems, several chapters have been devoted to epidemiological research and related issues. (shrink)