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 Part I of his paper Cooper gives indisputable evidence regarding Plato's use of the man-made image as a step to the apprehension of a Form under discussion, whether that image be in fact a diagram or a model, or simply a verbal picture, such as his imaginative account of Justice within a community, which we find used to provide us with in Republic 443 c 4 ff. However, Cooper goes on to assure us that the divided-line figure offers us (...) only three types of object: ‘We have three kinds of objects which differ from one another in clearness and esteem, firstly, the Forms, secondly, the objects of ordinary sense-perception, and thirdly, images, shadows and reflections.’ Now the admitted fact that, as he notes, Republic 10 gives the same three orders of reality, does not entirely absolve Cooper from all the implications of Plato's decision to divide his line into four parts rather than three; for it is made quite clear in 509 b 6–10 that the Form of the Good, is the source of being as well as of knowledge, so the Line must also classify both. (shrink)

I. By Ictus we mean in this paper the sounds emphasized in the pattern of an utterance in the given language under discussion. So in languages like Chinese which depend on variation of tone we mean that the high notes in the intonation tune of a sentence or the rhythmic scheme of a verse carry an ictus; while in a language based, like English, on speech stress, we mean that the syllables uttered most loudly and clearly bear the ictus. Again, (...) some languages, such as Italian, emphasize a syllable by a combination of stress and raised pitch, so in these languages we say that the syllables so emphasized receive the ictus. Lastly, in a language like ancient Greek or Vedic Sanskrit where quantity is decisive in utterance, the syllables which receive emphasis are the long ones, and thus it is these which have an ictus. (shrink)

This brief enquiry concerns two main questions: how and why Sulpicius' law differed from a similar prior rogation of the same year, which he had vetoed; and the probable authorship of the latter.

Discussion starts from Tac. Ann. 4.56, where in a.d. 26 ambassadors from Smyrna, with those of other communities in Asia, present their city's case for selection as the site of the province's cult of Tiberius, and plead a lengthy record of loyalty and past officia to Rome, dating back to the foundation at Smyrna of a temple to Urbs Roma in 195 B.C. amid the tensions with Antiochus III of Syria. Tacitus proceeds.

On any view, the Aristotelian account of Athens' constitutional history between victory over the Persian invaders and Ephialtes' reforms of the Areopagus and indeed beyond must be regarded as factually grudging and difficult to follow. Worse, current orthodoxy1 convicts it of a major chronological blunder for assigning a part in those reforms, which it places securely and beyond doubt correctly in the archonship of Konon, to Themistokles, who had been ostracized from the city perhaps as early as 473/2 and in (...) any case by 467/62. (shrink)

Applied or practical ethics is perhaps the largest growth area in philosophy today, and many issues in moral, social, and political life have come under philosophical scrutiny in recent years. Taken together, the essays in this volume – including two overview essays on theories of ethics and the nature of applied ethics – provide a state-of-the-art account of the most pressing moral questions facing us today. Provides a comprehensive guide to many of the most significant problems of practical ethics Offers (...) state-of-the-art accounts of issues in medical, environmental, legal, social, and business ethics Written by major philosophers presently engaged with these complex and profound ethical issues. (shrink)