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)

Providing the most thorough coverage available in one volume, this comprehensive, broadly based collection offers a wide variety of selections in four major genres, and also includes a section on film. Each of the five sections contains a detailed critical introduction to each form, brief biographies of the authors, and a clear, concise editorial apparatus. Updated and revised throughout, the new Fourth Edition adds essays by Margaret Mead, Russell Baker, Joan Didion, Annie Dillard, and Alice Walker; fiction by Nathaniel Hawthorne, (...) Ursula K. LeGuin, Anton Chekov, James Joyce, Katherine Mansfield, F. Scott Fitzgerald, William Faulkner, Alice Walker, Louise Erdrich, Donald Barthelme, and James McPherson; poems by John Donne, Robert Browning, Walt Whitman, Edwin Arlington Robinson, e.e. cummings, Langston Hughes, W.H. Auden, Philip Levine, and Louise Gluck; and plays by August Wilson, Marsha Norman, Wendy Wasserstein, and Vaclav Havel. The chapter devoted to film examines the relation of film to literature and gives the complete screenplay for Citizen Kane plus close analysis of a scene from the film. With its innovative structure, comprehensive coverage, and insightful and stimulating presentation of all kinds of literature, this is an anthology readers will turn to again and again. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:The Environmental Genome Project and BioethicsRichard R. Sharp (bio) and J. Carl Barrett (bio)Eight years ago, the Kennedy Institute of Ethics Journal published a brief selection by Eric Juengst (1991) entitled “The Human Genome Project and Bioethics.” That essay introduced and described the Ethical, Legal, and Social Implications (ELSI) Program at the National Center for Human Genome Research. 1 Since that time, the ELSI program has grown to (...) become one of the largest and most well regarded bioethics programs in the country, sponsoring the work of hundreds of researchers and coordinating bioethics activities both nationally and internationally (Marshall 1996; Meslin, Thomson, and Boyer 1997). In 1991, however, Juengst, the first director of the ELSI program, had no way of anticipating these developments. Juengst’s goal in his essay was simply to highlight some of the moral and social issues that were emerging as focal points for the ELSI program. Looking back, the issues he outlined may seem vague and overly broad. At the time, however, the essay served an important purpose, to identify areas requiring additional study and thereby to serve as a guide to others interested in joining in these discussions.In many ways, Juengst’s article serves as an inspiration to those of us working on a new bioethics project. The National Institute of Environmental Health Sciences (NIEHS) recently launched a multi-year project aimed at better understanding genetic influences on environmentally associated diseases (Albers 1997; Brown and Hartwell 1998; Cannon 1997; Kaiser 1997). This project, known as the Environmental Genome Project (EGP), plans to identify and study a number of common genetic variants that may play an important role in determining how individuals respond to environmental exposures. NIEHS hopes that the information learned through the EGP will be instrumental in developing more effective disease-prevention strategies and intervention programs. Following the precedent developed in connection with the Human Genome Project, NIEHS also plans to address the moral and social implications of the EGP. Efforts in this regard include sponsoring workshops and conferences to address such issues, as well as supporting research on the ethical, legal, and social implications of the EGP. Through this work, NIEHS hopes to anticipate potential problems before [End Page 175] they arise and to develop policies that maximize the benefits of the research while avoiding potential misuses of the information learned.In exploring the social implications of the EGP, we at NIEHS are very fortunate to be able to draw upon the work being done by the ELSI program at the National Human Genome Research Institute (NHGRI), as well as the ever-expanding bioethics literature that has been sparked by the ELSI program. Still, there is much to be done and this is an exciting time for those of us involved with the EGP. Many of the ethical, legal, and social implications of the project are only beginning to become clearer, and several of these issues appear quite different from the sorts of concerns that have previously been discussed in connection with other types of genetic research.This essay highlights some of the ethical, legal, and social implications that are emerging as important focal points for the Environmental Genome Project. Like Juengst’s 1991 paper, the goal of this article is to provide an overview of current areas of interest and to encourage others to join us in thinking about these difficult issues.The Environmental Genome ProjectIndividuals differ greatly in their responses to chemicals, drugs, radiation, smoking, alcohol, and other environmental exposures. These differential responses are the result of complex interactions between many factors, including an individual’s genetic make-up, age, sex, nutritional status, and overall health. The EGP aims to better understand the genetic basis of differential responses to environmental exposures. The vast majority of diseases, many forms of cancer, for example, are the consequence of both environmental and genetic contributions (Perera 1997). Hence, understanding the relationships between genetic variation and response to environmental exposure is important for understanding the causes of human disease and is crucial for the development of effective disease-prevention strategies.The EGP and projects like it represent a new stage of genomic research. It is expected that the Human Genome Project will complete... (shrink)

This initial volume in a series of new translations of Plato’s works includes a general introduction and interpretive comments for the dialogues translated: the _Euthyphro, Apology, Crito, Meno, Gorgias, _and _Menexenus. _ _ _“Allen’s work is very impressive. The translations are readable, lucid, and highly accurate. The general introduction is succinct and extremely clear. The discussion of the dating of the dialogues is enormously useful; there has previously been no brief account of these issues to which one could refer the (...) student. Finally, the particular introductions are first rate: fine jobs of clear philosophical and historical explanation—succinct and yet sophisticated, both close to the text and philosophically incisive.”—Martha Nussbaum, _Brown University_ “This is an important work that deserves our respect and attention.”—_Ethics _ _ _“This and the promised succeeding volumes will probably become the standard English version of the complete dialogues…. The commentaries take advantage of the best scholarship, judge judiciously between divergent views, and often introduce new and brilliant interpretations. This is true both in the area of philosophy and in that of literary criticism.”—Anthony C. Daly, S.J., _Modern Schoolman_ _ _“Allen is a superb translator, whose elegantly simple yet precise language gives access to Plato both as a philosopher and as a literary artist.”—_Library Journal__ _ “An important event in the world of scholarship.”—_London Review of Books_ _ _R.E. Allen is professor of classics and philosophy at Northwestern University. (shrink)

In this systematic introduction to the philosophy of Charles S. Peirce, the author focuses on four of Peirce's fundamental conceptions: pragmatism and Peirce's development of it into what he called 'pragmaticism'; his theory of signs; his phenomenology; and his theory that continuity is of prime importance for philosophy. He argues that at the centre of Peirce's philosophical project is a unique form of metaphysical realism, whereby continuity and evolutionary change are both necessary for our understanding of experience. In his final (...) chapter Professor Hausman applies this version of realism to contemporary controversies between anti-realists and anti-idealists. Peirce's views are compared to those of such contemporary figures as Davidson, Putnam, and Rorty. The book will be of particular interest to philosophers concerned with American philosophy and current debates on realism as well as linguists working in semiotics. (shrink)

In this systematic introduction to the philosophy of Charles S. Peirce, the author focuses on four of Peirce's fundamental conceptions: pragmatism and Peirce's development of it into what he called 'pragmaticism'; his theory of signs; his phenomenology; and his theory that continuity is of prime importance for philosophy. He argues that at the centre of Peirce's philosophical project is a unique form of metaphysical realism, whereby continuity and evolutionary change are both necessary for our understanding of experience. In his final (...) chapter Professor Hausman applies this version of realism to contemporary controversies between anti-realists and anti–idealists. Peirce's views are compared to those of such contemporary figures as Davidson, Putnam, and Rorty. The book will be of particular interest to philosophers concerned with American philosophy and current debates on realism as well as linguists working in semiotics. (shrink)

Physical Relativity explores the nature of the distinction at the heart of Einstein's 1905 formulation of his special theory of relativity: that between kinematics and dynamics. Einstein himself became increasingly uncomfortable with this distinction, and with the limitations of what he called the 'principle theory' approach inspired by the logic of thermodynamics. A handful of physicists and philosophers have over the last century likewise expressed doubts about Einstein's treatment of the relativistic behaviour of rigid bodies and clocks in motion in (...) the kinematical part of his great paper, and suggested that the dynamical understanding of length contraction and time dilation intimated by the immediate precursors of Einstein is more fundamental. Harvey Brown both examines and extends these arguments, after giving a careful analysis of key features of the pre-history of relativity theory. He argues furthermore that the geometrization of the theory by Minkowski in 1908 brought illumination, but not a causal explanation of relativistic effects. Finally, Brown tries to show that the dynamical interpretation of special relativity defended in the book is consistent with the role this theory must play as a limiting case of Einstein's 1915 theory of gravity: the general theory of relativity.Appearing in the centennial year of Einstein's celebrated paper on special relativity, Physical Relativity is an unusual, critical examination of the way Einstein formulated his theory. It also examines in detail certain specific historical and conceptual issues that have long given rise to debate in both special and general relativity theory, such as the conventionality of simultaneity, the principle of general covariance, and the consistency or otherwise of the special theory with quantum mechanics. Harvey Brown' s new interpretation of relativity theory will interest anyone working on these central topics in modern physics. (shrink)

On Becoming an Effective Teacher presents the final unpublished writings of Rogers and as such has a unique historical value. It also documents the research results of four highly relevant, related but independent studies which comprise the biggest collection of data ever accumulated to test a person-centred theory in the field of education. This body of comprehensive research on effective teaching was accomplished over a twenty-year period in 42 States in the U.S. and in six other countries including the UK, (...) Germany, Brazil, Canada, Israel, and Mexico, and is highly relevant to the concerns of teachers, psychologists, students, and parents. The principal findings of the research in this book show that teachers and schools can significantly improve their effectiveness through programs focusing on facilitative interpersonal relationships. Teachers who either naturally have, or are trained to have empathy, genuineness (congruence), and who prize their students (positive regard) create an important level of trust in the classroom and exert significant positive effects on student outcomes including achievement scores, interpersonal functioning, self-concept, and attendance. The dialogues between Rogers and Lyon offer a unique and timeless perspective on teaching, counselling and learning. The work of Reinhard Tausch on person-centered teaching to counselors, parents, athletics, and even textbook materials, as well as research on the interactions of teachers and students, is among the most thorough and rigorous research ever accomplished on the significance and potential of a person-centered approach to teaching and learning. (shrink)

The distinction between discovery and justification is ambiguous. This obscures the debate over a logic of discovery. For the debate presupposes the distinction. Real discoveries are well established. What is well established is justified. The proper distinctions are three: initial thinking, plausibility, and acceptability. Logic is not essential to initial thinking. We do not need good supporting reasons to initially think of an hypothesis. Initial thoughts need be neither plausible nor acceptable. Logic is essential, as Hanson noted, to both plausibility (...) and acceptability. An hypothesis needs good supporting reasons to be either plausible or acceptable. Such reasons need not be relative to the particular scientific theory undergoing test at the time. There is no fundamental difference between reasons relevant to plausibility and acceptability. The difference is one of degree. Acceptability requires more than plausibility. (shrink)

Based on author's dissertation--Yale University.

Humans have undergone a long evolutionary history of violent agonistic exchanges, which would have placed selective pressures on greater body size and the psychophysical systems that detect them. The present work showed that greater body size in humans predicted increased knockout power during combative contests (Study 1a-1b: total N = 5,866; Study 2: N = 44 openweight fights). In agonistic exchanges reflective of ancestral size asymmetries, heavier combatants were 200% more likely to win against their lighter counterparts because they were (...) 200% more likely to knock them out (Study 2). Human dominance judgments (total N = 500 MTurkers) accurately tracked the frequency with which men (N = 516) knocked out similar-sized adversaries (Study 3). Humans were able to directly perceive a man’s knockout power because they were attending to cues of a man’s body size. Human dominance judgments—which are important across numerous psychological domains, including attractiveness, leadership, and legal decision-making—accurately predict the likelihood with which a potential mate, ally, or rival can incapacitate their adversaries. (shrink)

Feyerabend claims that what is perceived depends upon what is believed ; and he maintains that among really efficient alternative theories "each theory will possess its own experience, and there will be no overlap between these experiences". According to Feyerabend "scientific theories are ways of looking at the world; and their adoption affects our general beliefs and expectations, and thereby also our experiences...". Toulmin, Hanson, and Kuhn concur with this view. Toulmin claims that men who accept different "ideals" and "paradigms" (...) will see different phenomena. He thinks theories not only give significance to facts, but also determine what facts are for us at all. Like Feyerabend, Toulmin asserts that "we see the world through" our fundamental concepts of science "to such an extent that we forget what it would look like without them". Indeed, both Feyerabend and Toulmin would have previous thinkers "live in an observational world very different from our own". Kuhn expresses quite similar views. He feels that. (shrink)

: When language is expressed metaphorically, metaphors seem to "say" something that has never seen said before. Some of them seem to express insights. What then are the constraints on their interpretations? Charles Peirce's semeiotic suggests a way to answer the question. Crucial to the answer is Peirce's account of semeiotic objects as two-fold, one side, the dynamic or "real" object to be interpreted, the other side, the immediate object, which is the dynamic object that has been interpreted. The interaction (...) account of metaphor is reviewed and related to Peirce's conception of semeiotic objects. The result is my suggestion that the dynamic objects to which metaphorical objects are directed are transformed into interpreted, immediate objects through the mediation of incipient immediate objects. Incipient immediate objects initially appear as dyadic objects recognized through identity expressions—e.g., "Juliet is the sun," which is not a classification but an identification of the referents of the subject and the predicate. The incipient mediating immediate object parallels the percipium referred to in Peirce's account of the formation of perceptual judgments, which are interpretations of percepts. (shrink)

When language is expressed metaphorically, metaphors seem to "say" something that has never seen said before. Some of them seem to express insights. What then are the constraints on their interpretations? Charles Peirce's semeiotic suggests a way to answer the question. Crucial to the answer is Peirce's account of semeiotic objects as two-fold, one side, the dynamic or "real" object to be interpreted, the other side, the immediate object, which is the dynamic object that has been interpreted. The interaction account (...) of metaphor is reviewed and related to Peirce's conception of semeiotic objects. The result is my suggestion that the dynamic objects to which metaphorical objects are directed are transformed into interpreted, immediate objects through the mediation of incipient immediate objects. Incipient immediate objects initially appear as dyadic objects recognized through identity expressions—e.g., "Juliet is the sun," which is not a classification but an identification of the referents of the subject and the predicate. The incipient mediating immediate object parallels the percipium referred to in Peirce's account of the formation of perceptual judgments, which are interpretations of percepts. (shrink)

In this article I discuss the justification of scientific change and argue that it rests on different sorts of invariance. Against this background I consider notions of observation, meaning, and regulative standards. I sketch an account of the rationale of scientific change which preserves the merits and avoids the shortcomings of the approach of Feyerabend, Hanson, Kuhn, Toulmin, and others. Each of these writers would hold that transitions from one scientific tradition to another force radical changes in what is observed, (...) in the meanings of the terms employed, and in the metastandards involved. They would claim that "incommensurable" replacement is what does, and should, occur during scientific "revolutions." Such writers, however, have trouble in comparing different scientific theories. My account permits different theories to be compared in various ways. These comparisons, I argue, are possible through appeal to "first-level" and "second-level" invariance. In this connection I argue that observation, meaning, and regulative standards should be, and in fact usually are, nontrivially invariant with respect to scientific change. (shrink)

There is a strong mystical strain running through the Neo-Platonic tradition. It arises from the claim that the One is absolutely transcendent, beyond all thought and all being, ineffable and incomprehensible. This claim readily appears in the doctrines of Plotinus, Iamblichus, and Damascius. It is, however, most carefully dealt with and receives its most systematic espousal from the celebrated Proclus of Athens. Proclus’ Commentary On The Parmenides is a polished espousal of the first hypothesis of Plato’s Parmenides. It is there (...) that he expresses his own view of the One and shows his acute sensitivity to logical problems arising from it. It will be my attempt here to examine the tenability of Proclus’ view of the One. In the course of this examination I will evaluate some of his solutions to the logical difficulties resulting from his position as to the One. I wish to argue that his position is beset with insurmountable difficulties and that his solutions to them are unsatisfactory. (shrink)

Pseudo-appeals to conscience stress that the dictates of conscience are always either morally obligatory or at least not morally wrong. These appeals are untenable. They result in an indefensible moral relativism. They should be abandoned.