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)

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)

Volume 10, Issue 2, June 2019, Page 237-245.

Over the last 50 years, the term professionalism has undergone a widespread expansion in its use and a semantic shift in its meaning. As a result, it is at risk of losing its descriptive and analytical value and becoming instead simply an empty evaluative label, a fate described by C. S. Lewis as ‘verbicide’. This article attempts to rescue professionalism from this fate by down-sizing its extension and reassigning some of its work to two other ethical domains, introduced as the (...) neologisms organizationalism and sur-moralism. Professionalism is defined as a morality based in system of obligations that are assumed by physicians over the course of their professional training and which primarily refer to two groups: patients and colleagues, including trainees. Organizationalism is also a morality, but the obligations are owed to the employing organization and on different grounds. A third ethical domain, here called sur-moralism, comprises actions that are not based in obligations. They are discretionary and potentially meritorious; they cannot be required by the profession or organization. This article presents a conceptual model of the three ethical domains and the shifting borders between them. One practical benefit of this typology is that physicians can more accurately understand the nature and sources of obligations that they are asked to accept, and when necessary prioritize them. Another is that physicians will be able to describe the potential tension between the three domains and understand how and why the borders between them can move. Both should help physicians to be more ethically oriented to their work settings. (shrink)

Legal moralists hold that the immorality of an action is a sufficient reason for the state to prevent it. Liberals in the tradition of Mill generally reject legal moralism. However, Larry Alexander has recently developed an argument that suggests that a class of legal restrictions on freedom that most liberals endorse is, and perhaps can only be, justified on moralistic grounds. According to Alexander, environmental restrictions designed to preserve nature or beauty are forms of legal moralism. In this paper, I (...) explore two liberal lines of response to Alexander’s argument. The first argues that an aesthetic interest is among our basic legally protectable interests. This argument claims that environmental and other regulations designed to protect beauty and nature are justified in order to prevent setbacks to this aesthetic interest. The second focuses on a democratic conception of the public interest. It holds that democratic communities are entitled, through their institutions, to shape the community and environment they live in. On this view, the community need not appeal to moralism to justify its adoption of environmental regulations, since in adopting such regulations it is simply enacting its collective preferences. On these grounds, I claim that Alexander’s case for the claim that aesthetic regulations can only be justified on moralistic grounds is much weaker than he takes it to be. (shrink)

A collection of essays examining the contentious, dynamic, and ethically complicated relationship between race and religion in Judaism. Includes perspectives from the fields of history, philosophy, sociology, ethics, religious studies, law, psychology, literary studies, and theology.

In lieu of an abstract, here is a brief excerpt of the content:PrefaceMost of the papers in this special issue of Diacritics were presented at a conference on the future of French studies organized at Cornell University with a special grant from the Office of the President, Hunter Rawlings III. The charge to the speakers was less to reflect on the situation of French studies in the American academy than to offer possibilities for the future, whether through programmatic argument or (...) illustration of the sort of work that might be undertaken under the banner of French studies. The editors have substituted for two papers from the conference that were already committed elsewhere two new papers from colleagues engaged in French studies at Cornell.The ongoing arguments about the future of French studies seem riven by a conflict of motives and aims. There are those who wish to confirm the dissolution of any fetishized notion of Frenchness, insisting on the multiplicity of francophonies and the fragmenting effects of globalization on anything that claims to be a specifically French identity. Conversely, there are those who promote French studies precisely as the defense of an irreducible specificity of things French, which is threatened by changes in the university and in the world and which the new field of French studies might have a chance of preserving. If these are not the options that our contributors embrace, it is not because they are insensible of their attractions—or of the beguiling possibility of combining them, by defining that essential Frenchness, to be pursued or preserved, as the dissolution of the idea of an essential Frenchness.One of the general aims of these papers is to promote and illustrate possibilities for novel kinds of reading and writing and for inventive modes of interdisciplinary study, which make French studies a lively field for students and teachers. But if there is a single substantial theme that runs through them all, it may be the mundane concern that Tom Conley calls “wondering what can be done to invigorate one of the richest of all literary canons.” How does that canon respond to the kinds of questions and issues that the unraveling and dissolution of boundaries—including those of France itself—have made possible? And should French studies, in the end, be conceived as the integration of the numerous interdisciplinary trajectories that depart from or traverse this canon or as a more distinctively specific practice for the study of everything French that is structured like a language?Copyright © 1999 The Johns Hopkins University Press... (shrink)

Introduces various distinctions: between the reasons why we should act, those for which we act, and the reasons why we act. It also distinguishes between Humeanism and anti‐Humeanism in the theory of motivation, psychologism, and anti‐psychologism in the theory of motivation, internalism, and externalism and desire‐based and value‐based theories of normative reasons.

Quevedo brings together a number of philosophical traditions in the Suenos. One chapter of the thesis examines Quevedo's use of Epicurean dream theory as well as the larger ramifications of the dream setting for the satires. Another chapter analyzes the exact nature of Quevedo's sceptical views and their classical sources with emphasis on the content of El mundo por de dentro. Included is a discussion of the moral philosophy presented in the Suenos, deriving primarily from Stoic sources. In each case, (...) Quevedo reconciles these classical influences with Christian doctrine, leading to a discussion in the thesis as to the exact nature of his Christian beliefs as they are expressed in the Suenos, i.e., whether Quevedo was indeed an existentialist and nihilist as many have labeled him. (shrink)

The debate concerning the moral permissibility of using human embryos in human embryonic stem cell (hESC) research has long centred on the question of the embryo's supposed right to life. However, in focussing only on this question, many opponents to hESC research have escaped rigorous scrutiny by making vague and unfounded appeals to the concept of moral respect in order to justify their opposition to certain hESC practices. In this paper, I offer a critical analysis of the concept of moral (...) respect, and its use to support the intuitively appealing principle of proportionality in hESC research. I argue that if proponents of this principle are to justify its adoption by appealing to the concept of moral respect, they must explain two things concerning the nature of the moral respect owed to embryos. First, they must explain which particular aspect of the embryo is morally relevant, and why. Second, they must explain why some uses of embryos in research fail to acknowledge what is morally relevant about the embryo, and thereby involve a violation of the moral respect that they are due. I shall show that providing such explanations may be more difficult than it first appears. (shrink)

Sartre's concept of ‘non-thetic awareness’ must be understood as equivalent to the concept of ‘nonconceptual content’ currently discussed in anglophone epistemology and philosophy of mind, since it could not otherwise play the role in the structure of ‘bad faith’, or self-deception, that Sartre ascribes to it. This understanding of the term makes sense of some otherwise puzzling features of Sartre's early philosophy, and has implications for understanding certain areas of his thought.

This book focuses on how we perceive, know and interpret culture across disciplinary boundaries. The study ranges from the Bible and classical works to those by and about men and women in Europe, the Americas and beyond of Native, African, European and different backgrounds.

In Matthew 23:1-3, Jesus commands His disciples and the crowd to listen to the scribes and Pharisees even while not imitating their actions. Many modern interpreters have lessened the force of Matthew 23:1-3 by an assumption of irony on the part of Jesus. We presume that God could never ordain this for His people. However, this easier reading may not be the best reading. A more straightforward interpretation, but one that is difficult to hear, suggests that at times we may (...) need to sit under bad leadership as means of receiving God’s Word. Pre-critical and modern interpreters provide an understanding of the words of Jesus that is consistent with a theology of God’s providence in times of transition and bad leadership. In addition, there are instances of His direction in both the Old and New Testaments that reinforce this challenging path. It is through this more faithful stance that we grow and flourish in difficult times. (shrink)

This book addresses the challenges of living together after empire in many post-colonial cities. It is organized in two sections. The first section focuses on efforts by people of multiple faiths to live together within their contexts, including such efforts within a neighborhood in urban Manchester; the array of attempts at creating multi-faith spaces for worship across the globe; and initiatives to commemorate divisive conflict together in Northern Ireland. The second section utilizes particular postcolonial methods to illuminate pressing issues within (...) specific contexts—including women’s leadership in an indigenous denomination in the variegated African landscape, and baptism and discipleship among Dalit communities in India. In the context of growing multiculturalism in the West, this volume offers a postcolonial theological resource, challenging the epistemologies in the Western academy. (shrink)

The second of three commentaries on “A Defense of Genetic Discrimination,” from the July‐August 2013 issue.

Con questa ricerca vorremmo soffermarci su quattro punti che riteniamo fondamentali per la comprensione dell'influenza delle fonti neoplatoniche nella Firenze del Quattrocento. Il punto di partenza è l'analisi dei rapporti tra i due massimi esponenti del neoplatonismo fiorentino: Pico della Mirandola e Marsilio Ficino, autori fondamentali non solo per le loro interpretazioni, ma anche per aver riscoperto e tradotto, dopo secoli di silenzio, i tesori del pensiero greco. Non si comprenderebbe l'influenza delle fonti neoplatoniche antiche nel Quattrocento senza rendere conto (...) del confronto – spesso molto aspro – tra i due protagonisti pricipali della riscoperta rinascimentale di Platone e di tutta la tradizione neoplatonica. Il secondo punto affronta un'importante interpretazione in senso tomista dell'opera di Pico, quella di Giovanni di Napoli, che aiuta ad intendere tanto le differenze tra il mirandolano e Ficino, quanto ad introdurre all'influenza importantissima dello Pseudo-Dionigi in tutto il dibattito filosofico del tardo Quattrocento. Il terzo punto cerca di affrontare un tema fondamentale: l'esigenza di definire e organizzare nuovi ordini del sapere. Dal recupero del passato emergevano nuove contraddizioni e nuove esigenze, non si trattava affatto di una semplice imitazione dell'antico, ma al contrario, significava farlo rivivere in nuove forme e costruire nuovi sistemi dei saperi capaci di rispondere alle esigenze culturali e politiche che stavano alla base della nascita del moderno. L'ultimo punto riguarda invece un'analisi specifica tra il pensiero di Giovanni Pico e lo Pseudo-Dionigi, discorso che ovviamente comporta anche l'analisi di altre fonti fondamentali, in particolare Damascio. Parole chiave: Neoplatonismo fiorentino, Giovanni Pico, della Mirandola, Marsilio Ficino, Pseudo-Areopagita. (shrink)

Book reviewed in this article: The Insanity Defense and the Trial of John W. Hinckley, Jr. By Lincoln Caplan.

For some contemporary historical theorists, the postmodernist movement in history and its nearly unilateral orientation towards language or discourse recently became subject to ‘the law of diminishing returns’ due to shifts in interests of philosophers and theorists of history at this time. Nevertheless, the contributions left by postmodernism in Western historical thought are too noticeable to be denied, even by those who have criticized it in the past. Frank Ankersmit is one of the few theorists that has been on both (...) sides; firstly, he swiftly tied his case to postmodernism, and secondly, he joined those who, then and now, think that postmodernism was nothing more than an irresponsible and irretrievable trend. Hence, the aim of this paper is to explore some of the particularities of Ankersmit’s affair with postmodernism, taking his metaphor of ‘the autumn of historiography’ as an example of the limits of this relationship and its eventual end. (shrink)

French end-of-life law aims at protecting patients from unreasonable treatments, but has been used to force caregivers to prolong treatments deemed unreasonable. We describe six cases (five intensi...