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)

Philosophy of history is not a subject which has hitherto attracted much attention in this country. Preoccupation with the methods and achievements of the natural sciences, and distaste for the sort of rationale of history as a whole which Hegel and others offered under the title in the early nineteenth century, have served to make most British philosophers accord its problems only the most casual recognition. It is therefore all the more interesting to find an English writer of unusual powers (...) both of argument and expression, who was himself an historian of distinction in his special field, devoting a large part of his philosophical thinking to the problems of historical knowledge and their wider implications. Unfortunately, R. G. Collingwood was not able to begin the major work on philosophy of history, to writing which, as we are told in the introduction to the present book, he had looked forward for twenty-five years, until his powers were seriously affected by bad health, and he did not live to complete it. But though the full results of his thinking on the subject are lost, we are now able, thanks to the skilful work of his friend Professor T. M. Knox, to study what is in effect an extensive interim report on it. Professor Knox has produced The Idea of History largely on the basis of lectures which Collingwood prepared in 1936, supplemented by two essays already published which date from the same period and a certain amount of material from the unfinished Principles of History written in 1939. (shrink)

The question I want to discuss is that of the sense and respects in which morality is strictly a matter for the individual. To hear some people talk you would think that it is wholly so. Not only do I have to make my own moral decisions; I have in a way to make them on my own terms, in so far as the rules I take to govern my actions are rules I have freely accepted, or at the least (...) not positively repudiated. In law I can be bound by statutes which I regard as abhorrent or even of whose content I am ignorant ; that a similar situation should obtain in morals is commonly treated as absurd. If I see nothing wrong with a certain practice, such as premarital sex or drug-taking, I can’t be brought morally to book for indulging in it. Morals is not solely a matter of personal taste, for the nature of moral judgment is such that the moral agent legislates not just for himself but for all who are similarly situated; equally, however, it is not something which can be externally enforced. There are no objective moral principles, plain for all to see, against which to measure moral error, and though there is fairly widespread agreement among the respectable that some forms of conduct are morally admirable and others morally deplorable, we are under no obligation to respect these “conventions.” A man’s only true obligation here is to follow his conscience and thus do what he takes to be right, in the light of the best information about the situation he can get. (shrink)

A re-examination of the anonymous Commentary on the Theaetetus, henceforth abbreviated K, is overdue. It may yet prove to be the most important document we possess for plotting the course of pre-Plotinian Platonism, and is by far the largest surviving portion of a pre-Plotinian commentary on a complete work of Plato. It offers us insights into the issues of the first century B.C. which are unparalleled in other extant Middle Platonist works, either because of the subject of the work and (...) its consequent tendency to bring to mind the epistemological debates between Philo of Larissa, Antiochus of Ascalon, and Aenesidemus, or because the author, whom we may call A, is writing at a time comparatively close to those debates. (shrink)

Excerpt from Essays on the Religion and Philosophy of the Hindus Called by the indulgence of this meeting to a chair, which I could have wished to have seen more worthily filled, upon so interesting an occasion as the first general meeting of a Society instituted for the important purpose of the advancement of knowledge in relation to Asia, I shall, with your permission, detain you a little from the special business of the day, while I draw your more particular (...) attention to the objects of the Institution, for the furtherance of which we are now assembled. To those countries of Asia, in which civilization may be justly considered to have had its origin, or to have attained its earliest growth, the rest of the civilized world owes a large debt of gratitude, which it cannot but be solicitous to repay; and England, as most advanced in refinement, is, for that very cause, the most beholden; and, by acquisition of dominion in the East, is bound by a yet closer tie. As Englishmen, we participate in the earnest wish, that this duty may be fulfilled, and that obligation requited; and we share in the anxious desire of contributing to such a happy result, by promoting an interchange of benefits, and returning in an improved state that which was received in a ruder form. About the Publisher Forgotten Books publishes hundreds of thousands of rare and classic books. Find more at www.forgottenbooks.com This book is a reproduction of an important historical work. Forgotten Books uses state-of-the-art technology to digitally reconstruct the work, preserving the original format whilst repairing imperfections present in the aged copy. In rare cases, an imperfection in the original, such as a blemish or missing page, may be replicated in our edition. We do, however, repair the vast majority of imperfections successfully; any imperfections that remain are intentionally left to preserve the state of such historical works. (shrink)