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)

So a frenzied matron cries out to Phoebus as she rushes through an appalled Rome. In CQ 34 , 454f. I pointed out that the words primos in ortus could not here bear their normal sense ‘to the far east’ , which in view of the next line would be geographically absurd, and, distraught as the lady was, even so highly improbable. I did, however, then think R. J. Getty right in taking the expression primos ortus as simply = ‘the (...) east’, and adding ‘the epithet primos appears to be otiose’. But I now feel very doubtful about the epithet being viewed as otiose in order that the words may denote Egypt; quite different are the passages noted in OLD primus 6 ‘belonging to the rising sun, eastern’, as Stat. Silv. 1.4.73 ‘occidiias primasque domos’ in the cited Sen. Oed. 116 ‘miles… ausus Eois equitare campis / figere et mundo tua signa primo’ the literal meaning is no doubt ‘on the world's first edge’ , but its development into ‘eastern’ is readily seen. Egypt, however, as viewed by Rome, is but the bare beginning of the east, and that is what primos must indicate above : see OLD primus 10 b ‘the nearest part of, the entrance, threshold, or sim., of, noting e.g. Ov. Fast. 1.717 ‘horreat Aeneadas et primus et ultimus orbis’, Cic. Fam. 3.6.2. ‘te in prima prouincia uelle esse, ut quam primum decederes’. In a characteristic departure from their stock meaning Lucan's words primos in ortus must then mean ‘to the threshold of the east’, i.e. the delta of the Nile, as explained in the next line : contrast 7.360 primo gentes oriente = ‘the nations of the far east’ . For Egypt viewed as the beginning of the east, cf. Mela 1.9 ‘Asiae prima pars Aegyptus’, Plin. Nat. 5.47 ‘[Africae] adhaeret Asia, quam patere a Canopico ostio [Nili] ad Ponti ostium Timosthenes…tradidit’, Mart. Cap. 6.675 ‘Aegyptus… Asiae caput, 3 quae una ab ostio Canopi ad ostium Ponti habet… milia passuum’; cf. the close association of Egypt with the east in Virg. Aen. 8.687 ‘Aegyptum uiresque Orientis’. For the varied use of the word primus should be noted too Luc. 9.413f. ‘nee… plus litora Nili / quam Scythicus Tanais primis a Gadibus absunt’, ‘from Gades in the far west’ , ‘Gades the first place in the west’ , i.e. the threshold of the Mediterranean. (shrink)

The text quoted above each note is that of the edition of Seneca's tragedies by Otto Zwierlein , OCT 1986; numerous passages are discussed in his Kritischer Kommentar zu den Tragüdien Senecas , Stuttgart, 1986; various textual suggestions were made in a correspondence with Zw. by B. Axelson . Other works on Seneca's tragedies, referred to by the scholar's name only, are: Text and translation: F. J. Miller, Loeb, 1917; L. Herrmann, Budé, 1924–6. Text with commentary: R. J. Tarrant, Agamemnon (...) , and Thyestes ; J. G. Fitch, Hercules Furens . Text with commentary and translation: Elaine Fantham, Troades ; A. J.Boyle, Phaedra. (shrink)

In spite of the seeming heterogeneity of topics in its title - Revolutions, Systems, and Theories - this volume purports to be something more than a random collection of Essays in Political Philosophy. The Colloquium of the Philosophy Department of the University of Western Ontario (29-31 Octo­ ber, 1971) at which initial versions of the first eight papers were delivered was entitled 'Political Theory'; and while the organizers anticipated and indeed welcomed topicality in the issues accorded priority arid in the (...) empirical evidence invoked, they were also hoping for a reasonably comprehensive explorat ion of some of the central issues of political philosophy. For this reason it was quickly decided that in such a field a philosophical focus on clarification of ordering concepts required the suppIement - and test - of researches into more particular subject maUers by social scientists. Thus, to speak in general terms (where the specializatlons and their taxonomies multi­ ply fissiparously!), contributors include political scientists, economists and sociologists (Barnard, Baston, Tullock, Rapoport) as well as philosophers (Scriven, Morgenbesser, Braybrooke, TayIor), and juxtaposed as proponents and commentators ·to generate exchanges across disciplinary frontiers. While the five additional invited papers are alI by professional philosophers, they extend the original Colloquium either by continuing controversy on its funda­ mental issues (e. g., Rubinoff, Nielsen, Roy) or by their continued explorations in what are acknowledged to be boundary areas (e. g., Schick, Wartofsky). The greatest topical emphasis is that on revolution. (shrink)

Ship design needs to respond to and attract an ever more design conscious society. However, little research has been conducted into perceptions of beauty and pleasure and how such perceptions can be usefully absorbed into ship design. Aesthetic consideration, is seen as a distraction from the bespoke nature of the ship design process and is often avoided, second guessed or left for external consultancy. The ship design discipline requires the nurturing of its own aesthetic methods, for future development, and to (...) adapt some of the aesthetic ideals found in architecture, art and design. This paper argues that philosophy can be effective in interpreting what the passenger finds attractive and pleasurable. To illustrate the philosophical approach proposed, the `Elbe SWATH’ and the `Oasis of the Seas’ are investigated and compared using theoretical resources from the culturally focused philosophy of `Functional Beauty’. Conclusions suggest that the interpretation of the end users most valued appreciations can lead to design directives that deliver subjective qualities of beauty - beauty similar to those seen in the pure aims of the Elbe SWATH’s purposeful work craft, or comparable to nature’s beauty and purity in aim. (shrink)

We used computer simulations to study the possible role of the dispersion of cellular coupling, refractoriness or both, in the mechanisms underlying cardiac arrhythmias. Local ischemia was first assumed to induce cell to cell dispersion of the coupling resistance (Case 1), refractory period (Case 2), or both of them (Case 3). Our numerical experiments based on the van Capelle and Durrer model showed that vortices could not be induced by cell to cell variations. With cellular properties dispersed in a patchy (...) way within the ischemic zone, a single activation wave could give rise to abnormal activities. This demonstrates the stability of the wave front under small inhomogeneities. Probabilities of reentry, estimated for the three cases cited above showed that a severe alteration of the coupling resistance may be an important factor in the genesis of reentry. Moreover, use of isochronal maps revealed that vortices were both stable and sustained with an alteration of the coupling alone or combined with a reduction of the action potential duration. Conversely, simulations with reduction of the refractoriness alone, inducing only transient patterns, could exhibit functionally determined reentries. (shrink)

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Mr Olding's recent attack on my exposition of the argument from design gives me an opportunity to defend the central theses of my original article. My article pointed out that there were arguments from design of two types—those which take as their premisses regularities of copresence and those which take as their premisses regularities of succession. I sought to defend an argument of the second type. One merit of such an argument is that there is no doubt about the truth (...) of its premisses. Almost all objects in the world behave in a highly regular way describable by scientific laws. Further, any scientific explanation of such a regularity must invoke some more general regularity. The most general regularities of all are, as such, scientifically inexplicable. The question arises whether there is a possible explanation of another kind which can be provided for them, and whether their occurrence gives any or much support to that explanation. I urged that we do explain some phenomena by explanation of an entirely different kind from the scientific. We explain states of affairs by the action of agents who bring them about intentionally of their own choice. Regularities of succession, as well as other phenomena may be explained in this way. Explanation of this kind I will term intentional explanation. Intentional explanation of some phenomenon E consists in adducing an agent A who brought E about of his own choice and a further end G which, he believed, would be forwarded by the production of E. (shrink)

An alleged moral right to informational privacy assumes that we should have control over information about ourselves. What is the philosophical justification for this control? I think that one prevalent answer to this question—an answer that has to do with the justification of negative rights generally—will not do.

On what grounds will the rational man become a Christian? It is often assumed by many, especially non-Christians, that he will become a Christian if and only if he judges that the evidence available to him shows that it is more likely than not that the Christian theological system is true, that, in mathematical terms, on the evidence available to him, the probability of its truth is greater than half. It is the purpose of this paper to investigate whether or (...) not this is a necessary and sufficient condition for the rational man to adopt Christianity. (shrink)