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)

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)

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)

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)

It is rarely, if at all, thought that Socrates committed suicide; but such was the case, or so I want to suggest. My suggestion turns not upon any new interpretation of ancient sources but rather upon seeking a determination of the concept of suicide itself.

R. G. Swinburne; XIII*—Personal Identity, Proceedings of the Aristotelian Society, Volume 74, Issue 1, 1 June 1974, Pages 231–247, https://doi.org/10.1093/arist.

This treatise on aesthetics criticizes various psychological theories of art, offers new theories and interpretations, and draws important inferences concerning ...

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.

In this article we show that it is possible to completely classify the degrees of r.e. bases of r.e. vector spaces in terms of weak truth table degrees. The ideas extend to classify the degrees of complements and splittings. Several ramifications of the classification are discussed, together with an analysis of the structure of the degrees of pairs of r.e. summands of r.e. spaces.

_Purpose._ This article reveals the importance of the analysis of the theory of generations to identify the essential characteristics of the phenomenon of youth. _Theoretical basis_ of this study is socio-philosophical anthropology, i.e. philosophical anthropology using certain methods of sociological, socio-psychological and ethnological research, as well as philosophical comprehension of the application of these methods in special sciences. _Originality._ The authors rethought the theoretical and practical potential of generational theory through its reconceptualization based on philosophical anthropology, which created an opportunity (...) to shift research attention from the attempts to identify superhistorical characteristics of youth to the identification of the essential nature of specific historical and sociocultural features of young people as representatives of a particular culture. _Conclusions._ Defining the youth phenomenon requires accounting at least three constraints that on the one hand, play a role of warnings that deter from theoretical and practical errors in the study of the youth phenomenon, and on the other hand, guidelines for identifying real, specific characteristics of youth as a social phenomenon. Limitations of theoretical and practical analysis of young people are as follows: first, the need to consider demographic data not as final, but only as initial and preliminary, such that require further substantive socio-cultural analysis; second, the inadmissibility of ignoring the cultural diversity of the manifestations of the youth phenomenon, instead the need to identify the special characteristics of youth of different ethnic, religious and other groups; third, the need to take into account the specifics of self-identification of those who identify themselves as young people as a social group. (shrink)

Informed choice is increasingly recognised as important in supporting patient autonomy and ensuring that people are neither deceived nor coerced. In cancer screening the emphasis has shifted away from just promoting the benefits of screening to providing comprehensive information to enable people to make an informed choice. Cancer screening programmes in the UK now have policies in place which state that it is their responsibility to ensure that individuals are making an individual informed choice. There is a need to evaluate (...) whether such policies mean that those people invited for screening are making informed choices, and how comprehensive information affects other variables such as uptake, cost effectiveness, and satisfaction. At the present time, there is no validated measure of informed choice in cancer screening. Such a measure could be used to evaluate the effectiveness of interventions to increase informed choice and levels of informed choice in a population invited for screening. It could encourage health professionals to be accountable. Factors important when measuring informed choice in cancer screening include an individual’s understanding of the limitations of screening, the ability to make an autonomous choice, and the difference between choice and behaviour. (shrink)

Media attention to retracted research suggests that a substantial number of papers are corrupted by misinformation. In reality, every paper contains misinformation; at issue is whether the balance of correct versus incorrect information is acceptable. This paper postulates that analysis of retracted research papers can provide insight into medical misinformation, although retracted papers are not a random sample of incorrect papers. Error is the most common reason for retraction and error may be the principal cause of misinformation as well. Still, (...) one-quarter of retracted papers are fraudulent, and misinformation may also arise through fraud. This paper hypothesises that error and fraud are the main sources of misinformation and that error is more common than fraud. Retraction removes misinformation from the literature; bias is non-retracted misinformation. Bias arises when scientific impropriety results in false research findings. Impropriety can involve experimental design, data collection, data analysis, or data presentation. Yet impropriety also arises through earnest error or statistical naiveté; not all bias is fraud. Several measures are proposed to minimise misinformation in the medical literature, including: greater detail in the clinical trial registry, with rigorous definition of inclusion and exclusion criteria and primary endpoints; clear statistical criteria for every aspect of clinical trials, especially sample size; responsibility for data integrity that accrues to all named authors; increased transparency as to how the costs of research were paid; and greater clarity as to the reasons for retraction. Misinformation can arise without malicious intent; authors of incorrect papers are owed a presumption of incompetence, not malice. (shrink)

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)

Background Clinical papers so flawed that they are eventually retracted may put patients at risk. Patient risk could arise in a retracted primary study or in any secondary study that draws ideas or inspiration from a primary study. Methods To determine how many patients were put at risk, we evaluated 788 retracted English-language papers published from 2000 to 2010, describing new research with humans or freshly derived human material. These primary papers—together with all secondary studies citing them—were evaluated using ISI (...) Web of Knowledge. Excluded from study were 468 basic science papers not studying fresh human material; 88 reviews presenting older data; 22 case reports; 7 papers retracted for journal error and 23 papers unavailable on Web of Knowledge. Overall, 180 retracted primary papers (22.8%) met the inclusion criteria. Subjects enrolled and patients treated in 180 primary studies and 851 secondary studies were combined. Results Retracted papers were cited over 5000 times, with 93% of citations being research related, suggesting that ideas promulgated in retracted papers can influence subsequent research. Over 28 000 subjects were enrolled—and 9189 patients were treated—in 180 retracted primary studies. Over 400 000 subjects were enrolled—and 70 501 patients were treated—in 851 secondary studies which cited a retracted paper. Papers retracted for fraud (n=70) treated more patients per study (p<0.01) than papers retracted for error (n=110). Conclusions Many patients are put at risk by retracted studies. These are conservative estimates, as only patients enrolled in published clinical studies were tallied. (shrink)