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)

Hegel introduced the Phenomenology of Mind as a work on the problem of knowledge. In the first chapter, entitled “Sense Certainty, or the This and Meaning,” he concluded that knowledge cannot consist of an immediate awareness of particulars ). The tradition discusses sense certainty in terms of this failure of immediate knowledge without, however, specifically addressing the problem of reference. Yet reference is distinct from knowledge in the sense that while there can be no knowledge of objects without reference, there (...) may be reference without knowledge. If that is the case, then the failure of immediate knowledge does not entitle us to conclude anything about the success or failure of reference. It is not surprising, then, that a few scholars have begun to examine sense certainty primarily as a thesis about reference. (shrink)

Hierarchical Bayesian models provide an account of Bayesian inference in a hierarchically structured hypothesis space. Scientific theories are plausibly regarded as organized into hierarchies in many cases, with higher levels sometimes called ‘paradigms’ and lower levels encoding more specific or concrete hypotheses. Therefore, HBMs provide a useful model for scientific theory change, showing how higher-level theory change may be driven by the impact of evidence on lower levels. HBMs capture features described in the Kuhnian tradition, particularly the idea that higher-level (...) theories guide learning at lower levels. In addition, they help resolve certain issues for Bayesians, such as scientific preference for simplicity and the problem of new theories. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:“Normalizing” Intersex Didn’t Feel Normal or Honest to Me.Karen A. WalshI am an intersex woman with Complete Androgen Insensitivity Syndrome (CAIS). My 57–year history with this has its own trajectory—mostly driven by medical events, and how I and my parents reacted. Most of my treatment by physicians has not been positive. It didn’t make me “normal” at all. I was born normal and didn’t require medical interventions. And by (...) the way, I’ve never been confused about who or what I am.Truthful disclosure didn’t come to me about my biology and what was done to me as an infant until I was 33, when I forced the issue by removing my medical records from my endocrinologist’s office. I learned that there was never full disclosure to my [End Page 119] parents either, and therefore there was no informed consent for the “corrective” surgeries performed on me as an infant. My parents were only told that their little girl would get cancer and would not have a normal development as a girl unless her “deformed ovaries” were removed, and that they should never discuss these problems with me. Thus, after having presented with an inguinal hernia and having exploratory surgery at age 16 months, my intra–abdominal testes were removed in a second surgery two months later. I was pronounced a “male pseudohermaphrodite,” a diagnosis that was shared neither with my parents nor with me.Years later, I discovered an article my surgeon published in 1960 in the Delaware Medical Journal about me and another intersex person he operated on (whom he labeled a “true hermaphrodite”). The article gives a very detailed pathology report of my gonads, but only two sentences regarding my welfare and the rationale for performing those surgeries. Dr. J. F. Kustrup wrote in this article, “These [two cases] emphasize the need for early diagnosis and treatment in order to avoid the possibility of malignant change and to permit these individuals to follow a normal psychosexual pattern.” And: “Hermaphroditism and pseudohermaphroditism are conditions in which early diagnosis and treatment are essential to avoid malignant degeneration and to allow the child some chance toward normal pyschic [sic] development.” I was grateful to find this article because it revealed the unfounded assumptions underpinning the recommendations for treatment, much of which continues today. Worse even than the sort of social prejudice that shapes treatment is the absence of evidence for what doctors treat as “necessary” interventions. For my syndrome, CAIS, there never was—and still is not—data to support the cancer scare, or the opinion that I’d be confused and not have a normal life.From about the age of four, I can remember being different and being stonewalled by my doctor and prevented by my parents from talking about it. The feelings and fears I tried to express were shushed away, and I could tell that my questions were upsetting everyone. Even if I had wanted to be complicit with their lame diversions and nonsensical explanations, the massive abdominal scars were there as a daily reminder and hinted at a very different story.The Road to Hell is Paved with Good IntentionsGrowing up, I was treated like a fascinoma and a lab rat at a major teaching hospital on the East Coast. All I learned from those doctors as a young kid was what it feels like to be ogled, photographed and probed by a roomful of white–coated male doctors. Dissociation made itself my friend, and helped me to cope through the annual genital and anal exams and probing. I thought I was a freak and I felt completely powerless to protect myself from them and their “care”.At my annual appointment at age 12, with my mom present, three doctors told me I was infertile. Learning that I couldn’t have kids really saddened and shocked me, but there was no opportunity to talk about my feelings—either that day, or any time afterward. I was told to stop crying. I remember them telling me that there was no one else like me and that this was a random genetic anomaly, thereby reinforcing the freakishness... (shrink)

This is a collection of sixteen essays by a diverse group of international scholars that offers a wide-ranging and contemporary perspective on the major aspects of Christian Wolff’s ethics. The volume focuses on Wolff’s German Ethics, arguably his most important and influential text on moral philosophy, but many of the chapters also consider the development of the basic tenets of Wolff’s moral theory in his later Latin writings. The contributions cover a range of topics, including the systematic structure of the (...) text itself and the relation between Wolff’s ethics and the preceding natural law tradition. Many chapters pay special attention to the core concepts of Wolff’s moral philosophy, such as obligation, perfection, the highest good, and happiness. Other notable topics include Wolff’s conception of moral judgment and moral education, as well as the role of psychology and anthropology in his ethical thought. The volume also contains discussion of the influence of Wolff’s ethics on subsequent figures such as C.A. Crusius, G.F. Meier, and Kant. As a whole, the volume seeks to establish the importance of Wolff’s German Ethics within the history of ethics as well as inspire others to engage with his thought. (shrink)

The Denjoy integral is an integral that extends the Lebesgue integral and can integrate any derivative. In this paper, it is shown that the graph of the indefinite Denjoy integral f↦∫xaf is a coanalytic non-Borel relation on the product space M[a,b]×C[a,b], where M[a,b] is the Polish space of real-valued measurable functions on [a,b] and where C[a,b] is the Polish space of real-valued continuous functions on [a,b]. Using the same methods, it is also shown that the class of indefinite Denjoy integrals, (...) called ACG∗[a,b], is a coanalytic but not Borel subclass of the space C[a,b], thus answering a question posed by Dougherty and Kechris. Some basic model theory of the associated spaces of integrable functions is also studied. Here the main result is that, when viewed as an ℝ[X]-module with the indeterminate X being interpreted as the indefinite integral, the space of continuous functions on the interval [a,b] is elementarily equivalent to the Lebesgue-integrable and Denjoy-integrable functions on this interval, and each is stable but not superstable, and that they all have a common decidable theory when viewed as ℚ[X]-modules. (shrink)

We examine recursive monotonic functions on the Lindenbaum algebra of EA. We prove that no such function sends every consistent φ to a sentence with deductive strength strictly between φ and (φ∧Con(φ)). We generalize this result to iterates of consistency into the effective transfinite. We then prove that for any recursive monotonic function f, if there is an iterate of Con that bounds f everywhere, then f must be somewhere equal to an iterate of Con.

Theravada Buddhism. A Social History from Ancient Times to Modern Colombo. Richard F. Gombrich. Routledge, London 1988. x, 237 pp. Hbk £20.00, pbk £7.95.

On the nature of Aristotle's Ethics, by R. A. Gauthier.--Reason, happiness, and goodness, by F. Siegler.--The nature of aims, by J. Dewey.--Thought and action in Aristotle, by G. E. M. Anscombe.--On forgetting the difference between right and wrong, by G. Ryle.--Aristotle and the punishment of psychopaths, by V. Haksar.--Suggested further readings (p. 121-123).

Portraits of Wittgenstein is a major collection of memoirs and reflections on one of the most influential and yet elusive personalities in the history of modern philosophy, Ludwig Wittgenstein. Featuring a wealth of illuminating and profound insights into Wittgenstein's extraordinary life, this unique collection reveals Wittgenstein's character and power of personality more vividly and comprehensively than ever before. With portraits from more than seventy-five figures, Portraits of Wittgenstein brings together the personal recollections of philosophers, students, friends and acquaintances, including Bertrand (...) Russell, G. E. Moore, F. R. Leavis, A. J. Ayer, Karl Popper, Friedrich von Hayek, G. H. von Wright, Rush Rhees, Freeman Dyson, G. E. M. Anscombe, Iris Murdoch, Mary Midgley and Mary Warnock. These authors testify to the life-long influence Wittgenstein had on the lives of those he met. Their fascinating memoirs, reflections and commentaries, often at odds with each other, reveal Wittgenstein's kindness, and how much genuine friendship meant to him, as well as his suffering and despair. They show too how the philosopher's ruthless honesty and uncompromising integrity often resulted in stern advice and harsh rebukes to friends and foes alike. Now available in a single, revised and updated volume, Portraits of Wittgenstein includes new selections, revised contributions, photographs, maps and introductory overviews that provide historical context to Wittgenstein's relationships with his intellectual and social circle. This collection of valuable and hard-to-find material is an indispensable resource for scholars and students of the life and work of Ludwig Wittgenstein. (shrink)

The dual-code proposal of number representation put forward by Cohen Kadosh & Walsh (CK&W) accounts for only a fraction of the many modes of numerical abstraction. Contrary to their proposal, robust data from human infants and nonhuman animals indicate that abstract numerical representations are psychologically primitive. Additionally, much of the behavioral and neural data cited to support CK&W's proposal is, in fact, neutral on the issue of numerical abstraction.