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)

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)

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)

Suffering evokes moral and metaphysical reflection, the bioethics of suffering concerns the proper ethos of living with suffering. Because empirical and philosophical explorations of suffering are imprisoned in the world of immanent experience, they cannot reach to a transcendent meaning. Even if religious and other narratives concerning the meaning of suffering have no transcendent import, they can have aesthetic and moral significance. This understanding of narratives of suffering and of their custodians has substantial ecumenical implications: chaplains can function as general (...) custodians of narratives and sustainers of a generic religious meaning. This understanding is contrary to traditional Christianity, which discloses a transcendent significance of human suffering found in a very particular history involving particular persons: Christ as the second Adam through the submission of the second Eve has taken on our nature so that we can be united with God. Human suffering is tied to human sin, not simply as a punishment for sin, much less as an opportunity to discharge a supposed temporal punishment due to sin. Human suffering is the result of our rebellious free choices. It provides an opportunity for humility and submission, so that, united to the cross of Christ, sin can be forgiven and suffering set aside in the Resurrection. Knowledge of this framing context for all human suffering is accessible not through rational argument. It is a knowledge garnered through repentance, purification of the heart, illumination by God's grace, and unification with God. Christian bioethics is embedded in the narrative of suffering, which is part of the history of salvation and which encompasses and places all of medicine in its terms. (shrink)

Because sin is anything that turns our heart from God, sins are both voluntary and jnvoluntary. As a consequence, double effect can only be adequately understood in a Christian context in which it is recognized that, even when evil is not willed, our involvement in its causation can still mar our hearts. The acknowledgement of involuntary sins resituates double effect so that the traditional Christian concern with spiritual harm and healing can be maintained. In this way, one can overcome the (...) underdeveloped Western theological appreciation of double effect, which ignores the effect on the heart of causing evil. (shrink)

Rather than revealing itself as a single, unified, ecumenical faith, Christianity is sundered with Christians united neither in one communion nor in one baptism. Christian Bioethics seeks to examine the traditional content-full moral commitments which the Christian faiths bring to life, sexuality, suffering, illness and death within the contexts of medicine and health care. Seeking to understand the differences which separate the bioethics of Roman Catholics, Protestants, and the Orthodox, Christian Bioethics explores the manners in which the faiths diverge. The (...) failure of the Enlightenment project to disclose a content-full communality that would bind mankind has left much to be reconsidered by Christians who face new ethical dilemmas in the novel guise of advances in health care technologies. (shrink)

In the face of the moral pluralism that results from the death of God and the abandonment of a God's eye perspective in secular philosophy, bioethics arose in a context that renders it essentially incapable of giving answers to substantive moral questions, such as concerning the permissibility of abortion, human embryonic stem cell research, euthanasia, etc. Indeed, it is only when bioethics understands its own limitations and those of secular moral philosophy in general can it better appreciate those tasks that (...) it can actually usefully perform in both the clinical and academic setting. It is the task of this paper to understand and reevaluate bioethics by understanding these limits. Academic bioethicists can analyze ideas, concepts, and claims necessary to understanding the moral questions raised in health care, assessing the arguments related to these issues, and provide an understanding of the different moral perspectives on bioethical issues. In the clinical setting, bioethicists can provide legal advice, serve as experts on IRBs, mediating disputes, facilitating decision-making and risk management, and clarifying normative issues. However, understanding this is only possible when one understands the history, genesis, and foundations of bioethics and its inability to provide a resolution to postmodern moral pluralism. (shrink)

This paper presents four different understandings of the family and their concomitant views of the authority of the family in pediatric medical decision making. These different views are grounded in robustly developed, and conflicting, worldviews supported by disparate basic premises about the nature of morality. The traditional worldviews are often found within religious communities that embrace foundational metaphysical premises at odds with the commitments of the liberal account of the family dominant in the secular culture of the West. These disputes (...) are substantial and ultimately irresolvable by sound rational argument because of the failure to share common foundational premises and rules of evidence. It is in light of these fundamental disagreements that there is a need to evaluate critically the claims and agenda advanced by the Convention on the Rights of the Child. (shrink)

Generalized anxiety disorder is among the world’s most prevalent psychiatric disorders and often manifests as persistent and difficult to control apprehension. Despite its prevalence, there is no integrative, formal model of how anxiety and anxiety disorders arise. Here, we offer a perspective derived from the free energy principle; one that shares similarities with established constructs such as learned helplessness. Our account is simple: anxiety can be formalized as learned uncertainty. A biological system, having had persistent uncertainty in its past, will (...) expect uncertainty in its future, irrespective of whether uncertainty truly persists. Despite our account’s intuitive simplicity—which can be illustrated with the mere flip of a coin—it is grounded within the free energy principle and hence situates the formation of anxiety within a broader explanatory framework of biological self-organization and self-evidencing. We conclude that, through conceptualizing anxiety within a framework of working generative models, our perspective might afford novel approaches in the clinical treatment of anxiety and its key symptoms. (shrink)

Marx's critique of political economy as a problem-posing framework Political economy and its critique Writing in the late, Friedrich Engels drew attention ...

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)