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)

The millennial interest in the fable told by Apuleius in The Golden Ass has produced periods of intense preoccupation. Of these uses of the legend none is more interesting, varied, and profound—none possesses greater implications for contemporary life and manners—than the obsessive concern of pre-Romantic and Romantic writers and artists. Hellenistic, Roman, and early Christian culture had produced at least twenty surviving statues of Psyche alone, some seven Christian sarcophagi that used the legend, and a set of mosaics on a (...) Christian ceiling in Rome from the early fourth century;1 and of course to late antiquity belongs the distinction of having produced the seminal telling of the tale by Apuleius in about A. D. 125. But what we possess from that remote time is thin and lacks the power to engage the modern spirit. The allegorizing and erotic responses made in the Renaissance, Mannerist, and Baroque culture produced monuments of painting that the later period cannot rival; but the impregnation of literature by the legend was slight, and the intellectual or moral content was often only a perfunctory and dutiful addendum. The revival of the story in the aesthetic movement of the late Victorians and early moderns has its examples of beauty, particularly in Rodin and in the lush harmonies and occasionally piercing melodies of César Franck's Psyché, a tone poem for chorus and orchestra; but the long retellings by Morris, Bridges, and John Jay Chapman oppress with luxuriant sweetness and remain of interest only as period pieces. · 1. See Elizabeth Hazelton Haight, Apuleius and His Influence , p. 164, and Maxime Collignon, "Essai sur les monuments grecs et romains . . . ," in Bibliothèque des écoles françaises d'Athène et de Rome , fasc. 2, pp. 285-446, esp. pp. 364, 436-38. Jean H. Hagstrum, John C. Shaffer Professor of English and Humanities at Northwestern University, is currently preparing a book on the theme of love in European literature and art from the mid-seventeenth century through the Romantic period. He is the author of books and articles on Blake and Samuel Johnson, and of The Sister Arts, a study of the relations of poetry and painting from antiquity through the eighteenth century. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:“The Whole Internal World His Own”: Locke and Metaphor ReconsideredS. H. ClarkWhy need I name thy Boyle, whose pious search, Amid the dark recesses of his works, The great Creator sought? And why thy Locke, Who made the whole internal world his own?Oh decus! Anglicae certe oh lux altera gentis!... Tu caecas rerum causas, fontemque severum Pande, Pater; tibi enim, tibi, veri magne Sacerdos, Corda patent hominum, atque altae (...) penetralia Mentis.Fourfold Annihilation & at the clangor of the Arrows of Intellect The innumerable Chariots of the Almighty appeard in Heaven And Bacon & Newton & Locke, & Milton & Shakespear & Chaucer1Two features of these encomia to John Locke, composed by James Thomson, Thomas Gray, and William Blake, are immediately striking. Firstly, they are delivered by poets in a tradition customarily seen as a reaction to the intellectual climate induced by Locke’s Essay, a book which Blake famously claimed to regard with “Contempt and Abhorrence.” 2 Secondly, the familiar and somewhat hackneyed characterizations of Locke as philosopher of common-sense, [End Page 241] empiricism, and liberal ideology are refreshingly absent. For Gray he is “veri magne Sacerdos,” great priest of truth; Thomson places him in a pantheon including Shakespeare, Milton, Spenser, and Chaucer; and this ranking is explicitly endorsed in Blake’s “Milton & Shakspear & Chaucer.” Comparable praise of Locke’s imaginative power is conspicuously absent from even the most generous tributes of recent commentators. 3Even if Locke’s philosophical contribution to a variety of debates is fully acknowledged, the question remains of why his major work, An Essay concerning Human Understanding, was held in such high popular esteem—veneration is not too strong a word—during the subsequent century. The text itself appears an improbable candidate for such canonization: George Saintsbury accused its prose of being “positively mean in every point of style,” 4 and certainly in comparison with the poised and lucid ironies of Berkeley and Hume, it cannot but appear prolix, diffuse, and repetitive. The chief (and frequently only) merit grudgingly accorded to it is of disarming informality. Rosalie Colie’s emphasis on the “exploitation of the generic and rhetorical possibilities in the essay form itself “ highlights the conscious manipulation of authorial distance through which Locke creates the effect of sprawling inclusiveness and incom-pletion, but at the expense of conceding that “in exchange for the frankness with which the essayist appeared to present his thinking self, he was allowed certain liberties from logical rigour.” 5 Though the suggestion that a major philosophical text seeks to evade “logical rigour” might seem damning enough, there is a still more insidious equation of Locke’s “middle-style,” his desire “to make, what I have to say, as easie and intelligible to all sort of Readers as I can,” with a complicity with the expectations of his audience. 6 Other critics, notably John Richetti, have put a more positive gloss on the “simple and fortuitously concocted circle of friends” to whom the Essay is addressed, but even these accounts have been obliged to stress the representative and consensual nature of Locke’s thought. 7 This view is perhaps most elegantly expressed by Leslie Stephen: “Locke ruled the thought of his own and the coming period [End Page 242] because he interpreted so completely the fundamental beliefs which had been worked out at this time. He ruled, that is, by obeying.” 8William Walker correctly observes that “identifying and interpreting metaphors of mind” in the Essay are “standard practices of mainstream philosophical commentary from Leibniz to Rorty,” but also notes that these analyses are usually concerned with the degree to which Locke’s reliance on figuration was at variance with and compromised his epistemological doctrine. 9 I would argue that the poetic tributes previously quoted offer a more suggestive and adequate guide to the original impact of his work. In order to substantiate this claim, I shall begin by examining Locke’s apparent renunciation of, yet paradoxical dependence upon metaphor; go on to look at the connection of the “Horizon” to the elegiac presentation of memory and the ethic of mental “Labour”; and conclude by analyzing the complex interdependence of candle and sun within the light imagery employed in the... (shrink)

This book explores how and when biology emerged as a science in Germany. Beginning with the debate about organism between Georg Ernst Stahl and Gottfried Leibniz at the start of the eighteenth century, John Zammito traces the development of a new research program, culminating in 1800, in the formulation of developmental morphology. He shows how over the course of the century, naturalists undertook to transform some domains of natural history into a distinct branch of natural philosophy, which attempted not (...) only to describe but to explain the natural world and became, ultimately, the science of biology. (shrink)

Kant’s philosophy of science takes on sharp contour in terms of his interaction with the practicing life scientists of his day, particularly Johann Blumenbach and the latter’s student, Christoph Girtanner, who in 1796 attempted to synthesize the ideas of Kant and Blumenbach. Indeed, Kant’s engagement with the life sciences played a far more substantial role in his transcendental philosophy than has been recognized hitherto. The theory of epigenesis, especially in light of Kant’s famous analogy in the first Critique, posed crucial (...) questions regarding the ‘looseness of fit’ between the constitutive and the regulative in Kant’s theory of empirical law. A detailed examination of Kant’s struggle with epigenesis between 1784 and 1790 demonstrates his grave reservations about its hylozoist implications, leading to his even stronger insistence on the discrimination of constitutive from regulative uses of reason. The continuing relevance of these issues for Kant’s philosophy of science is clear from the work of Buchdahl and its contemporary reception. (shrink)

A veritable tidal shift in Herder scholarship has taken place over the last quarter century, primarily but not exclusively in German. This review essay seeks to evoke the richness and vitality of this revival with the hope of persuading American academics that some ill-founded opinions still circulating concerning Herder's "irrationalism" and chauvinistic, even racist nationalism, and his philosophical naivety and literary effrontery, might at last be put to rest. The recent revival has brough sharply to the fore two crucial aspects (...) of Herder. First, there is the contribution of Herder's thought to the emergent cultural and social sciences. Second, for Herder the "science of man" was also a natural science: the division between the humanities and the natural sciences that has been such a hallmark of the age from Kant until very recently did not exist for Herder. (shrink)

Reconstructions of Kant are prominent in the contemporary debate over naturalism. Given that this naturalism rejects a priori principles, Kant's anti-naturalism can best be discerned in the “critical turn” as a response to David Hume. Hume did not awaken Kant to criticize but to defend rational metaphysics. But when Kant went transcendental did he not, in fact, go transcendent? The controversy in the 1990s over John McDowell's Mind and World explored just this suspicion: the questions of the normative force (...) of reason and of the ontological “space of reasons” vis- -vis the world. “Bald naturalism” appears to “extrude” rationality both ontologically and epistemologically from the natural world. Kant sought to discriminate a transcendental middle ground, safe from either extrusion. But was Kant's notion of the autonomy and spontaneity of reason as metaphysically innocent as McDowell's critics would have it? Situating Hume and naturalism in the eighteenth-century German context can help us understand the “critical turn” more accurately. While Hume recognized procedural proprieties for reflection, he did not believe in their a priori necessity. Initially, Kant shared that view. What assimilating Leibniz and Locke in the late 1760s garnered for Kant—the simultaneous spontaneity and self-transparency of reason—seemed to provide a means for overcoming Hume's skepticism and establishing a new foundation for metaphysics. Accordingly, all of the efforts of modern Kantianism notwithstanding, there is more than a whiff of the transcendent in Kant's transcendentalism. (shrink)

The two theories that revolutionized physics in the twentieth century, relativity and quantum mechanics, are full of predictions that defy common sense. Recently, we used three such paradoxical ideas to prove “The Free Will Theorem” (strengthened here), which is the culmination of a series of theorems about quantum mechanics that began in the 1960s. It asserts, roughly, that if indeed we humans have free will, then elementary particles already have their own small share of this valuable commodity. More precisely, if (...) the experimenter can freely choose the directions in which to orient his apparatus in a certain measurement, then the particle’s response (to be pedantic—the universe’s response near the particle) is not determined by the entire previous history of the universe. Our argument combines the well-known consequence of relativity theory, that the time order of space-like separated events is not absolute, with the EPR paradox discovered by Einstein, Podolsky, and Rosen in 1935, and the Kochen-Specker Paradox of 1967 (See [2].) We follow Bohm in using a spin version of EPR and Peres in using his set of 33 directions, rather than the original configuration used by Kochen and Specker. More contentiously, the argument also involves the notion of free will, but we postpone further discussion of this to the last section of the article. Note that our proof does not mention “probabilities” or the “states” that determine them, which is.. (shrink)

There is an unspoken distinction in ethical criteria in bioethics. On the one hand, there are criteria that can be used with discretion and judgment by an individual or small group of people like a...

In this issue, McCarthy, Homan and Rozier make the case for re-stablishing the relationship between theological and secular bioethics. I find MHR to be quite...

This chapter discusses the various meanings of the two critical ideas in this book and compares them. These critical ideas are “religion” and “public bioethics”. The chapter focuses most of all not on the different religious roles, but on what we think “public bioethics” is or should be.

This two-part article examines whether Sartre's final interviews, recorded in L'Espoir maintenant [ Hope Now ], indicate a final turn to belief through an overview of his engagement with the idea of God throughout his career. In Part 1 we examine Sartre's early atheism, but note the pervasive nature of secularised Christian metaphors and concepts in his religion of letters and the centrality of man's desire to be God in Being and Nothingness . His theoretical writings seek to refute the (...) idea of God, but in doing so God is paradoxically both absent and present. In Part 2 we assess his anti-theism and consider his final encounter with theism in L'Espoir maintenant, arguing that it is part of Sartre's long-term engagement with the idea of God. (shrink)

Volume 19, Issue 7, July 2019, Page 32-34.

The address of the President to his colleagues at the Medieval Academy is an invitation to speak about a subject close to the heart. I was told by the aunt who met me at the boat when I returned from Persia at the age of fourteen — a typical Kipling child, leaving my family on the other side of the world and returning home to school — that when she asked me what I was going to do when I grew (...) up, I said firmly, “I am going to teach Chaucer.” Well, it has been my privilege to study and teach and edit and write about Chaucer for nearly half a century. So there is no subject that I could speak about closer to my heart. (shrink)

The notion of Trieb, constitutive for Blumenbach’s greatest conceptual intervention, the Bildungstrieb, intentionally separated it from the other Bildungskräfte that had been identified in the physical world. This discrimination proved decisive for Kant. Thus we must endeavor to reconstruct the source and the significance of Blumenbach’s conceptual departure. My argument will be that in his turn to Trieb, Blumenbach drew upon the pioneering work of Hermann Reimarus. Thus, my argument will have three components: first, the conceptualization of Trieb in Reimarus; (...) second, the introduction of that term into Blumenbach’s own theorizing, in the notion Bildungstrieb; and, finally, how that figured in the reception of Blumenbach by Kant. (shrink)

This book is a study of comparative philosophy and theology. The themes are the critical issues arising from the modern interpretation of Confucian doctrine as they confront the Christian beliefs of the nineteenth and twentieth centuries.

In a recent essay, Donald Dripps advanced what he calls a “commodification theory” of rape, offered as an alternative to understanding rape in terms of lack of consent. Under the “commodification theory,” rape is understood as the expropriation of sexual services, i.e., obtaining sex through “illegitimate” means. One aim of Dripps's effort was to show the inadequacy of consent approaches to understanding rape. Robin West, while accepting Dripps's critique of consent theories, criticizes Dripps's commodification approach. In its place, West suggests (...) a more phenomenological approach. The author argues that neither Dripps nor West offers convincing critiques of consent-based theories; the alternatives they offer presuppose the vitality of a consent-based approach to understanding rape; and that both Dripps and West consistently conflate more general moral and political issues with that of the nature of rape. (shrink)

Ankersmit's articulation of a postmodern theory of history takes seriously both the strengths of traditional historicism and the right of historians to decide what makes sense for disciplinary practice. That makes him an exemplary interlocutor. Ankersmit proposes a theory of historical "representation" which radicalizes the narrative approach to historiography along the lines of poststructuralist textualism. Against this postmodernism but invoking some of his own arguments, I defend the traditional historicist position. I formulate criticisms of the theory of reference entailed in (...) his notion of "narrative substance," of his master analogy of historiography with modern painting, and finally of his characterization of historical hermeneutics. In each case I find him guilty of the hyperbole which he himself cautions against. While it is true that historical narratives cannot be taken to be transparent, in taking them to be opaque Ankersmit puts himself in an untenable position. Finally, Ankersmit seeks to buttress his theoretical case by an interpretation of the new cultural historical texts of authors like Davis and Ginzburg. While this is a concreteness heartily to be welcomed in philosophers of history, I cannot find his construction of this new school's work plausible. (shrink)

Few outstanding questions in the human behavioral sciences are timelier or more urgently debated than the evolutionary source of religious behaviors and beliefs. Byproduct theorists locate the origins of religion in evolved cognitive defaults and transmission biases. Others have argued that cultural evolutionary processes integrated non-adaptive cognitive byproducts into coherent networks of supernatural beliefs and ritual that encouraged in-group cooperativeness, while adaptationist models assert that the cognitive and behavioral foundations of religion have been selected for at more basic levels. Here, (...) we survey these differing approaches, noting their respective strengths and weaknesses. We then advance a novel model that centers on the ability of language to generate alternative worlds independent of immediate empirical facts, and thus highlight the similarities between religious belief and the modes of cognition that underlie institutions in general. The institutional cognition model of religion accounts for some of the shortcomings of extant approaches and draws attention to the human ability to create non-empirical worlds; that is, worlds that are imaginary. Both religious beliefs and institutional facts—such as jurisdictional borders—are non-empirical assertions, yet they are socially accepted as truths and reified through ritual and behavior. One type of non-empirical, linguistically generated belief—supernatural agent belief—is particularly effective for stabilizing systems of arbitrary norms by rooting them in deontic rather than utilitarian reasoning. The evolutionary roots and continued persistence of religion are thus functions of the capacity for humans to generate cognitive alternatives to empirical reality, and the need to stably coordinate those alternative conceptions. (shrink)