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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)

This is a protocol for a Cochrane Review (Intervention). The objectives are as follows: -/- The main aim of this review will be to assess the effects of changing practitioner empathy or patient expectations for all conditions. The main objective is to conduct a systematic review of randomised trials where the intervention involves manipulating either (a) practitioner empathy or (b) patient expectations, or (c) both.

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 invaluable resource is the first one-volume, in-depth, comprehensive history of modern science ever published.

A subspace V of an infinite dimensional fully effective vector space V ∞ is called decidable if V is r.e. and there exists an r.e. W such that $V \oplus W = V_\infty$ . These subspaces of V ∞ are natural analogues of recursive subsets of ω. The set of r.e. subspaces forms a lattice L(V ∞ ) and the set of decidable subspaces forms a lower semilattice S(V ∞ ). We analyse S(V ∞ ) and its relationship with L(V (...) ∞ ). We show: Proposition. Let U, V, W ∈ L(V ∞ ) where U is infinite dimensional and $U \oplus V = W$ . Then there exists a decidable subspace D such that U |oplus D = W. Corollary. Any r.e. subspace can be expressed as the direct sum of two decidable subspaces. These results allow us to show: Proposition. The first order theory of the lower semilattice of decidable subspaces, Th(S(V ∞ )), is undecidable. This contrasts sharply with the result for recursive sets. Finally we examine various generalizations of our results. In particular we analyse S * (V ∞ ), that is, S(V ∞ ) modulo finite dimensional subspaces. We show S * (V ∞ ) is not a lattice. (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)

Biologically motivated computing seeks to transfer ideas from the biosciences to computer science. In seeking to make transfers it is helpful to be able to appreciate the metaphors which people use. This is because metaphors provide the context through which analogies and similes are made and by which many scientific models are constructed. As such, it is important for any rapidly evolving domain of knowledge to have developments accounted for in these terms. This paper seeks to provide one overview of (...) the process of modelling and shows how it can be used to account for a variety of biologically motivated computational models. Certain key ideas are identified in the subsequent analysis of biological sources, notably, systemic metaphors. Three important aspects of biological thinking are then considered in the light of computer science applications: biological organization, the cell, and models of evolution. The analysis throughout the paper is descriptive rather than formalized so that a large variety of potential applications may be considered. (shrink)

Recognising and responding appropriately to emotions is critical to adaptive psychological functioning. Psychopathic traits (e.g. callous, manipulative, impulsive, antisocial) are related to differences in recognition and response when emotion is conveyed through facial expressions and language. Use of emotional music stimuli represents a promising approach to improve our understanding of the specific emotion processing difficulties underlying psychopathic traits because it decouples recognition of emotion from cues directly conveyed by other people (e.g. facial signals). In Experiment 1, participants listened to clips (...) of emotional music and identified the emotional content (Sample 1, N = 196) or reported on their feelings elicited by the music (Sample 2, N = 197). Participants accurately recognised (t(195) = 32.78, p <.001, d = 4.69) and reported feelings consistent with (t(196) = 7.84, p <.001, d = 1.12) the emotion conveyed in the music. However, psychopathic traits were associated with reduced emotion recognition accuracy (F(1, 191) = 19.39, p <.001) and reduced likelihood of feeling the emotion (F(1, 193) = 35.45, p <.001), particularly for fearful music. In Experiment 2, we replicated findings for broad difficulties with emotion recognition (Sample 3, N = 179) and emotional resonance (Sample 4, N = 199) associated with psychopathic traits. Results offer new insight into emotion recognition and response difficulties that are associated with psychopathic traits. (shrink)

The ratification of the United Nations Convention on the Rights of the Child (UNCRC) demands that those participating nations, adopt the aims of the convention as state responsibilities toward their child citizens. The central premise of the convention is clear: that it is the right of all children to develop to their full potential. The authors propose six basic interdependent developmental requirements if the child is to reach ‘full potential’. Without prioritising any one need, but instead concentrating on the facilitation (...) of complete care of the child, the paper aims to examine how the UNCRC may finally be realised. This is achieved by highlighting several key situations and associated factors, which contribute to deficient care. Whilst the factors leading to the creation of such situations are often culturally specific, the consequences for the child, and the implications for care providers (parents, aid agencies, and policy makers), are often very similar within and between continents. (shrink)