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)

Een wijsgerig-methodologische studie welke zich alleen bezighoudt met het van de ervaring afhankelijke karakter van het empirisch onderzoek.

Building on a well-developed philosophy of language, Shibles proposes a theory of metaphor. Whereas one philosophy of language may regard metaphor as an inadequate or fallacious form of reasoning, another may consider it to be the very foundation of language. Shibles’ views lie in the latter direction, and he employs Wilbur Urban’s philosophy of language, presented in his Language and Reality, to develop his theory. Urban’s importance lies in his avoidance of reducing the philosophy of language to symbolic logic and (...) recognition of the importance of metaphor, symbol, and analogy. Also significant for a theory of metaphor is the fact that Urban saw a "high evaluation" of language as being more adequate than a "low evaluation" of language. (shrink)

In his last major work, the posthumously published Crisis of European Sciences, Husserl presented what he described as a new path into transcendental phenomenology: the path through the "life-world" on which objective science is founded. To make objective science intelligible, Husserl held, we must inquire back into the world of everyday involvement and experience from which it emerges; this inquiry leads in turn to a thematization of the subjective structures through which the always "pre-given" life-world is itself constituted. Husserl’s demand (...) for a return to the life-world has been the subject of much discussion in the twenty-five years since the publication of the Crisis. Yet debate over the precise sense and ultimate significance of the demand continues. In this most recent contribution, E. Ströker has gathered ten essays originally presented at a 1978 conference of prominent German and American scholars. At least some of the essays should prove helpful to Husserl specialists and others interested in Husserl’s concept of the life-world. (shrink)

P D Walsh; Value Education in a Pluralist Society, Journal of Philosophy of Education, Volume 10, Issue 1, 30 May 2006, Pages 24–33, https://doi.org/10.1111/j.1.

Collection of essays around the work of H.L.A. Hart.

A repulsive core force is derived which, assuming π mesons are the field particles, gives binding energies in good agreement with binding energies per nucleon of heavy nuclei. The physical model consists of a field of relatively short range, in which emission of a π meson by a nucleon and subsequent absorption by a neighboring nucleon is equivalent to a potential well. The binding energy at the equilibrium spacing of the nucleons is the self-energy of the π mesons, which is (...) calculated by analogy with classical electric fields. (shrink)

Purpose The search for cause of death is important to improve knowledge and provide answers for the relatives of the deceased. Medical autopsy following unexplained death in hospital is one way to identify cause of death but is difficult to carry out routinely. Post mortem sampling (PMS) of tissues via thin biopsy needle or ‘mini incisions’ in the skin may be a useful alternative. A study was undertaken to assess how this approach is perceived by intensive care doctors and also (...) to evaluate how this practice is considered in ethical terms in France. Methods A study of PMS practices immediately after death in 10 intensive care departments was performed. The medical director of each centre was interviewed by telephone and asked to describe practices in their unit and to outline the questions raised by this practice. Results PMS is routinely performed in 70% of the units which responded, without systematically obtaining formal consent and without precise rules for communicating results. Approaches to PMS differed between centres, but all physicians felt that PMS is useful for the scientific information it gives and also for the information it provides for relatives. All physicians regret the lack of standards to structure PMS practices. Conclusion Information from post mortem examinations is important for society to inform about causes of death, for doctors to improve practices and for decision-makers responsible for organising care. Debate persists regarding the balance between individual rights and community interests. It is suggested that an approach for identifying cause of death could easily be integrated into the relationship between carers and relatives, provided full transparency is maintained. (shrink)

We propose a model mechanism for the initiation and spatial positioning of teeth primordia in the alligator, Alligator mississippiensis. Detailed embryological studies by Westergaard and Ferguson have shown that jaw growth plays a crucial role in the developmental patterning of the tooth initiation process. Based on biological data we develop a dynamic patterning mechanism, which crucially includes domain growth. The mechanism can reproduce the spatial pattern development of the first seven teeth primordia in each half jaw of A. mississippiensis. The (...) results for the precise spatio-temporal sequence compare well with experiment. Simulation of the model also predicts that certain transplantations can alter the spatial sequence of teeth primordia initiation. (shrink)

Context The conduct of medical research led by Northern countries in developing countries raises ethical questions. The assessment of research protocols has to be twofold, with a first reading in the country of origin and a second one in the country where the research takes place. This reading should benefit from an independent local ethical review of protocols. Consequently, ethics committees for medical research are evolving in Africa. Objective To investigate the process of establishing ethics committees and their independence. Method (...) Descriptive study of 25 African countries and two North American countries. Data were recorded by questionnaire and interviews. Two visits of ethics committee meetings were conducted on the ground: over a period of 3 months in Kigali (Rwanda) and 2 months in Washington DC (USA). Results 22 countries participated in this study, 20 from Africa and two from North America. The response rate was 80%. 75% of local African committees developed into national ethics committees. During the last 5 years, these national committees have grown on a structural level. The circumstances of creation and the general context of underdevelopment remain the major challenges in Africa. Their independence could not be ensured without continuous training and efficient funding mechanisms. Institutional ethics committees are well established in USA and in Canada, whereas ethics committees in North America are weakened by the institutional affiliation of their members. Conclusion The process of establishing ethics committees could affect their functioning and compromise their independence in some African countries and in North America. (shrink)