The rapid rise of international collaborative science has enabled access to genomic data. In this article, it is argued that to move beyond mapping genomic variation to understanding its role in complex disease aetiology and treatment will require extending data sharing for the purposes of clinical research translation and implementation.

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)

Francis J. Ambrosiso begins with sentence that is either self-effacing or alarming “Truly, I do not know why I must write this book, so I must begin by asking for your forgiveness for having done son without knowing why and therefore, necessarily, without knowing how.” An Associate Professor of Philosophy at Georgetown University, Ambrosio believes “the difference the book makes is this: it traces and remarks in the texts of Dante and Derrida two episodes in the history of forgiveness” (p. (...) xi). (shrink)

The remarks I wish to make upon the Thucydides scholia in Bâle University MS. no. E III 4 will be clearer if prefaced by an outline history of the scholia to Thucydides in general.The editio princeps contained no scholia. They made their first appearance in the following year as an appendix to the Aldine Gemistius and Herodian. The same scholia were then reprinted in the Juntine edition as a frame to the text. In the Hervagian edition of Camerarius they were (...) relegated to the end, and Camerarius claims in his prefatory epistle to have expended some trouble in emending them. Henceforward the same corpus of scholia, unchanged save for occasional emendation, passes on from edition to edition, either framing the text, as in Stephanus, or beneath it, as in Stephanus, Hudson, Duker, Gottleber-Bauer-Beck. (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)

Here we discuss the challenge posed by self-organization to the Darwinian conception of evolution. As we point out, natural selection can only be the major creative agency in evolution if all or most of the adaptive complexity manifest in living organisms is built up over many generations by the cumulative selection of naturally occurring small, random mutations or variants, i.e., additive, incremental steps over an extended period of time. Biological self-organization—witnessed classically in the folding of a protein, or in the (...) formation of the cell membrane—is a fundamentally different means of generating complexity. We agree that self-organizing systems may be fine-tuned by selection and that self-organization may be therefore considered a complementary mechanism to natural selection as a causal agency in the evolution of life. But we argue that if self-organization proves to be a common mechanism for the generation of adaptive order from the molecular to the organismic level, then this will greatly undermine the Darwinian claim that natural selection is the major creative agency in evolution. We also point out that although complex self-organizing systems are easy to create in the electronic realm of cellular automata, to date translating in silico simulations into real material structures that self-organize into complex forms from local interactions between their constituents has not proved easy. This suggests that self-organizing systems analogous to those utilized by biological systems are at least rare and may indeed represent, as pre-Darwinists believed, a unique ascending hierarchy of natural forms. Such a unique adaptive hierarchy would pose another major challenge to the current Darwinian view of evolution, as it would mean the basic forms of life are necessary features of the order of nature and that the major pathways of evolution are determined by physical law, or more specifically by the self-organizing properties of biomatter, rather than natural selection. (shrink)

Alexandre Koyre was one of the most prominent historians of science of the twentieth century. The standard interpretation of Koyre is that he falls squarely within the internalist camp of historians of science-that he focuses on the history of the ideas themselves, eschewing cultural and sociological interpretations regarding the influence of ideologies and institutions on the development of science. When we read what Koyre has to say about his historical studies (and most of what others have said about them), we (...) find him embracing and championing this Platonic view of his work. Ultimately I think this interpretation of Koyre's history of science is lopsided and in need of correction. I claim, rather, that a careful reading of Koyre's work suggests that a tension exists between internal and external methodological considerations. The external considerations stem from Koyre's commitment to the unity of human thought and the influence he admits that the 'transscientifiques' (philosophy, metaphysics, religion) have on the development of science. I suggest in conclusion then, that if we are to put a philosophical label on his work, rather than 'Platonist', as has been the custom, 'Hegelian' makes a better fit. (shrink)