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)

Throughout the biological and biomedical sciences there is a growing need for, prescriptive ‘minimum information’ (MI) checklists specifying the key information to include when reporting experimental results are beginning to find favor with experimentalists, analysts, publishers and funders alike. Such checklists aim to ensure that methods, data, analyses and results are described to a level sufficient to support the unambiguous interpretation, sophisticated search, reanalysis and experimental corroboration and reuse of data sets, facilitating the extraction of maximum value from data sets (...) them. However, such ‘minimum information’ MI checklists are usually developed independently by groups working within representatives of particular biologically- or technologically-delineated domains. Consequently, an overview of the full range of checklists can be difficult to establish without intensive searching, and even tracking thetheir individual evolution of single checklists may be a non-trivial exercise. Checklists are also inevitably partially redundant when measured one against another, and where they overlap is far from straightforward. Furthermore, conflicts in scope and arbitrary decisions on wording and sub-structuring make integration difficult. This presents inhibit their use in combination. Overall, these issues present significant difficulties for the users of checklists, especially those in areas such as systems biology, who routinely combine information from multiple biological domains and technology platforms. To address all of the above, we present MIBBI (Minimum Information for Biological and Biomedical Investigations); a web-based communal resource for such checklists, designed to act as a ‘one-stop shop’ for those exploring the range of extant checklist projects, and to foster collaborative, integrative development and ultimately promote gradual integration of checklists. (shrink)

Background: The traditional approach to resolving ethics concerns may not address underlying organisational issues involved in the evolution of these concerns. This represents a missed opportunity to improve quality of care “upstream”. The purpose of this study was to understand better which organisational issues may contribute to ethics concerns. Methods: Directed content analysis was used to review ethics consultation notes from an academic children’s hospital from 1996 to 2006 (N = 71). The analysis utilised 18 categories of organisational issues derived (...) and modified from published quality improvement protocols. Results: Organisational issues were identified in 68 of the 71 (96%) ethics consult notes across a range of patient settings and reasons for consultation. Thirteen of the 18 categories of organisational issues were identified and there was a median of two organisational issues per consult note. The most frequently identified organisational issues were informal organisational culture (eg, collective practices and approaches to situations with ethical dimensions that are not guided by policy), policies and procedures (eg, staff knows policy and/or procedural guidelines for an ethical concern but do not follow it) and communication (eg, communication about critical information, orders, or hand-offs repeatedly does not occur among services). Conclusions: Organisational issues contribute to ethical concerns that result in clinical ethics consults. Identifying and addressing organisational issues such as informal culture and communication may help decrease the recurrence of future similar ethics concerns. (shrink)

Ethics, communication skills, and the law ('practice skills') are important in all aspects of modern health care. Doctors and nurses must be sensitive to the ethical aspects of their work and understand the legal framework within which clinical decisions are made. Well developed skills of communication, with patients, their relatives and other members of the clinical team, are a key feature of good clinical practice Until recently, the important of practice skills has been relatively neglected in health care education. This (...) situation is changing. The UK General Medical Council, for example, has recently identified three aspects as part of the core of the medical course, and the move to degree courses in nursing has led to an increasing focus of practice skills in nurse education. The Oxford Practice Skills Project (OPSP) team have developed a course, within the University of Oxford Clinical School, which covers the teaching of practice skills in an integrated manner. This course is widely recognized as one of the most systematic developments of education in these areas. This manual describes the OPSP course in detail and provides teaching materials. Although developed initially for medical students, it should be helpful to all those involved in teaching ethics, communication skills, and law in health care. Each Seminar is described in detail Tutors' guides are provided Student handouts are included Contains guidelines for introducing 'practice skills' into a busy clinical curriculum Includes over forty case histories for teaching and examination Gives details of many useful sources and resources Details a variety of teaching methods together with their advantages and disadvantages Provides an ethics teaching toolkit for clinical teachers new to this area Readers are welcome to photocopy any part of this manual for their own teaching. (shrink)

The present paper describes a number of ethical quandaries facing the implementors of motivational interventions in organizational settings. A critical analysis of the traditional solutions to these issues within the organizational literature finds them lacking for want of considering unwitting cognitive biases and self presentational doublespeak, both of which may result in the rights of research participants being underprotected. The establishment of an Institutional Review process, loosely analogized from the biomedical and behavioral science research traditions, is suggested as a means (...) of protecting the rights of research participants as well as humanizing future motivational interventions. (shrink)

I am interested in extending modal calculi by adding propositional quantifiers, given by the rules for quantifier introduction: provided that p does not occur free in A.

This article draws on scientific explanations of obesity to motivate the creation of a system of paternalistic public health interventions into the obesity epidemic. Libertarian paternalists argue that paternalism is warranted in light of the cognitive limits of human decision-making abilities. There are further, specific biological limits on our capacity to choose and maintain a healthy diet. These biological facts strengthen the general motivation for libertarian paternalism. As a consequence, the creation of a system of paternalistic public health interventions into (...) the obesity epidemic is warranted. (shrink)

Study of Samayasāra, treatise on Jaina philosophy by Kundakunda.

We can gain fresh insights into aspects of criminal liability by focusing first on the prior topic of criminal responsibility, and on the relational dimensions of responsibility: responsibility is responsibility for something, to someone. We are criminally responsible as citizens, to our fellow citizens, for committing 'public' wrongs: I discuss the difficulty of giving determinate content to this idea of public wrongs, and the way in which, whereas moral responsibility is typically strict, criminal responsibility is not. Finally, I explore the (...) grounds on which defendants might deny that they are criminally responsible before the courts that seek to try them. (shrink)

Three arguments are proposed against the idea that ordinary talk about the mind constitutes a folk psychology, a sort of prescientific theory which explains human behaviour and which is ripe for replacement by a neurological or computational theory with better scientific credentials. First, not all talk of the mind is introduced to explain in the way assumed by those who think that mental talk hypothesizes inner processes to explain behaviour. Second, the individuation of the behaviour which is explained by the (...) inner processes itself requires reference to ?mental? states such as intentions or desires. Consequently the project is circular. Finally, scientific theory is a practice with a history which may be matched in the case of ordinary talk of the mind. Certainly ordinary talk of motives, intentions, and thoughts may be infected by the theorizing of economists and sociologists et al., but it is impossible that all talk of the mind should be theoretical in this way. (shrink)

In _Sentient Flesh _R. A. Judy takes up freedman Tom Windham’s 1937 remark “we should have our liberty 'cause... us is human flesh" as a point of departure for an extended meditation on questions of the human, epistemology, and the historical ways in which the black being is understood. Drawing on numerous fields, from literary theory and musicology, to political theory and phenomenology, as well as Greek and Arabic philosophy, Judy engages literary texts and performative practices such as music and (...) dance that express knowledge and conceptions of humanity appositional to those grounding modern racialized capitalism. Operating as critiques of Western humanism, these practices and modes of being-in-the-world—which he theorizes as “thinking in disorder,” or “poiēsis in black”—foreground the irreducible concomitance of flesh, thinking, and personhood. As Judy demonstrates, recognizing this concomitance is central to finding a way past the destructive force of ontology that still holds us in thrall. Erudite and capacious, _Sentient Flesh _offers a major intervention in the black study of life. (shrink)

Discussions of responsibility typically focus on the person who is held responsible: what are the conditions or criteria of responsibility; what can be done to or demanded of a person who is responsible? This paper shifts focus onto those who hold, rather than those who are held, responsible: what do we owe to those whom we hold responsible? After distinguishing responsibility as answerability from responsibility as liability, it attends mainly to the former, and points out the ways in which it (...) is multiply relational: I am responsible for something to someone who has the standing to call me to account for it, under the norms of some particular practice. Responsibility as thus understood is also reciprocal: if you are to be answerable to me, I must treat you with a certain respect, attend seriously to your answer, and be ready to answer to you myself. The paper explores some of the implications of this point both for our moral dealings with each other, and for criminal law and the criminal trial. (shrink)

Nigel Walker’s first principle of criminalization declares that ‘Prohibitions should not be included in the criminal law for the sole purpose of ensuring that breaches of them are visited with retributive punishment’. I argue that we should reject this principle, for ‘mala prohibita’ as well as for ‘mala in se’: conduct should be criminalized in order to ensure (as far as we reasonably can) that those who engage in it receive retributive punishment. In the course of the argument, I show (...) why we should not see the criminal law as consisting in ‘prohibitions’; I explain different species of mala prohibita, and show how their commission does involve genuine wrongdoing; and I show the importance of distinguishing the question of regulation from that of sanction. (shrink)

After distinguishing different species of Legal Moralism I outline and defend a modest, positive Legal Moralism, according to which we have good reason to criminalize some type of conduct if it constitutes a public wrong. Some of the central elements of the argument will be: the need to remember that the criminal law is a political, not a moral practice, and therefore that in asking what kinds of conduct we have good reason to criminalize, we must begin not with the (...) entire realm of wrongdoing, but with conduct falling within the public realm of our civic life; the need to look at the different processes of criminalization, and to ask what kinds of consideration can properly figure in those processes; the need to attend to the relationship, and the essential differences, between criminal law and other modes of legal regulation. (shrink)

The author's motivation for constructing the calculi of this paper\nis so that time and tense can be "discussed together in the same\nlanguage" (p. 282). Two types of enriched propositional caluli for\ntense logic are considered, both containing ordinary propositional\nvariables for which any proposition may be substituted. One type\nalso contains "clock-propositional" variables, a,b,c, etc., for\nwhich only clock-propositional variables may be substituted and that\ncorrespond to instants or moments in the semantics. The other type\nalso contains "history-propositional" variables, u,v,w, etc., for\nwhich only history-propositional variables may (...) be substituted and\nthat correspond to maximally linearly ordered subsets of instants.\nThis second type is for tense logics in which time is not linear\nand where at any moment there may exist alternative future courses\nof events. Quantifiers are included in both types but only for clock-\nand history-propositional variables. However, these quantifiers are\ngiven an essentially substitutional interpretation. In addition,\nbesides each clock-propositional variable being true at exactly one\ninstant, the semantics requires that for each instant there be at\nleast one clock-propositional variable true at that instant, which\nin effect amounts to having each instant of the model "denoted" in\nthe formalism by some clock-propositional variable. Thus it is not\nsurprising that quantification over clock-propositional variables\nturns out to have a "well behaved first-order semantics" (p. 284).\n{One axiom relating history- with clock-propositions seems to need\nrevision: CKTauTbuAUabUba. Since the clock-propositional variables\nmight be true at the same instant the consequent should include an\nalternative, namely, LCab.} Besides the standard truth-functional\nand tense operators G,H,F,P, the author includes L for "it is\nalways the case that". The model-theoretic earlier-than relation\nordering instants and the semantic truth-at (an instant) relation\nare formalized by Uab and Taα (for a wff α) which\nare defined respectively as LCbPa (whenever the clock-proposition\nb is the case the clock-proposition a was the case) and LCaα\n(α is the case whenever the clock-proposition a is the case).\nBecause the future tense operators are definable in terms of U\nand T and the latter are definable in terms of L and P, the\ndual of H, the author notes that his completeness proofs can be\nrestricted to L and H as primitive and with the future tense\noperators used for other interpretations, especially Prior, A.'s\nindeterminist "it will be the case that", where time is not linear.\nThe author concludes with some rather technical observations showing\nthat "in ordinary tense logics the instants are nonstandard elements\nof the models. This provides", according to the author, "a semantic\npressure to build the instants into tense logic, so that they will\nappear as standard elements in the models" (p. 283). (shrink)

He then proceeds with an examination of the picture theory developed by Wittgenstein, Carnap, and Goodman, and concludes with an examination of Patricia Churchland, Ruth Millikan, Robert Cummins, and Mark Rollins. The use of the historical development of representationalism to pose a central problem in contemporary cognitive science is unique.