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)

Throughout the biological and biomedical sciences there is a growing need for, prescriptive ‘minimum information’ (MI) checklists specifying the key information to include when reporting experimental results are beginning to find favor with experimentalists, analysts, publishers and funders alike. Such checklists aim to ensure that methods, data, analyses and results are described to a level sufficient to support the unambiguous interpretation, sophisticated search, reanalysis and experimental corroboration and reuse of data sets, facilitating the extraction of maximum value from data sets (...) them. However, such ‘minimum information’ MI checklists are usually developed independently by groups working within representatives of particular biologically- or technologically-delineated domains. Consequently, an overview of the full range of checklists can be difficult to establish without intensive searching, and even tracking thetheir individual evolution of single checklists may be a non-trivial exercise. Checklists are also inevitably partially redundant when measured one against another, and where they overlap is far from straightforward. Furthermore, conflicts in scope and arbitrary decisions on wording and sub-structuring make integration difficult. This presents inhibit their use in combination. Overall, these issues present significant difficulties for the users of checklists, especially those in areas such as systems biology, who routinely combine information from multiple biological domains and technology platforms. To address all of the above, we present MIBBI (Minimum Information for Biological and Biomedical Investigations); a web-based communal resource for such checklists, designed to act as a ‘one-stop shop’ for those exploring the range of extant checklist projects, and to foster collaborative, integrative development and ultimately promote gradual integration of checklists. (shrink)

Dr. Elisabeth Kübler-Ross is credited as one of the first clinicians to formalize recommendations for working with patients with advanced medical illnesses. In her seminal book, On Death and Dying,...

This volume offers the first-ever complete English translation of Leibniz’s Dissertatio De Arte Combinatoria together with a critical edition of the original Latin text on fa...

Conspiracy theories and conspiracy theorists have been accused of a great many sins, but are the conspiracy theories conspiracy theorists believe epistemically problematic? Well, according to some recent work, yes, they are. Yet a number of other philosophers like Brian L. Keeley, Charles Pigden, Kurtis Hagen, Lee Basham, and the like have argued ‘No!’ I will argue that there are features of certain conspiracy theories which license suspicion of such theories. I will also argue that these features only license a (...) limited suspicion of these conspiracy theories, and thus we need to be careful about generalising from such suspicions to a view of the warrant of conspiracy theories more generally. To understand why, we need to get to the bottom of what exactly makes us suspicious of certain conspiracy theories, and how being suspicious of a conspiracy theory does not always tell us anything about how likely the theory in question is to be false. (shrink)

A remarkable feature of the philosophical work on conspiracy theory theory has been that most philosophers agree there is nothing inherently problematic about conspiracy theories (AKA the thesis of particularism). Recent work, however, has challenged this consensus view, arguing that there really is something epistemically wrong with conspiracy theorising (AKA generalism). Are particularism and generalism incompatible? By looking at just how much particularists and generalists might have to give away to make their theoretical viewpoints compatible, I will argue that particularists (...) can accept many of the concerns that motivate generalism because generalism can never be about ‘all’ conspiracy theories without being either ahistorical or apolitical. In the end generalist critiques are best seen as useful guidelines or considerations for the appraising of particular conspiracy theories. (shrink)

In this paper I interrogate the notion of `debunking conspiracy theories’, arguing that the term `debunk’ carries with it pejorative implications, given that the verb `to debunk’ is commonly understood as `to show the wrongness of a thing or concept’. As such, the notion of `debunking conspiracy theories’ builds in the notion that such theories are not just wrong but ought to be shown as being wrong. I argue that we should avoid the term `debunk’ and focus on investigating conspiracy (...) theories. Looking at recent research work in epistemology on conspiracy theory, I argue that the best way to avoid talk of `debunking’ conspiracy theories is by working with a non-pejorative definition of `conspiracy theory’, and forming communities of inquiry which allow us to investigate the warrant of such theories without the prejudice associated with working with a pejorative definition. (shrink)

Woodger first gives a rough account of the "Boole-Frege" movement in modern logic and persuasively argues as to the importance of formalized language-systems for the methodology of science. Some of these arguments are as follows: A natural language such as English, he notes, "is not only used for purposes of communication in the scientific sense. It is also used for the writing of poetry, for religious devotion, for political controversy, and for persuading people to buy some of the products of (...) industrial activity which they would not otherwise want. But these pursuits make demands upon language which are very different from those made by science. The requirements of science prove on investigation to be quite surprisingly meagre and the excessive riches of a natural language like English are a source of embarrassment. They tempt us to employ linguistic devices borrowed from extra-scientific usages which can have unfortunate consequences. Metaphors, for example, with which some branches of biology abound, are often suggestive and may be harmless enough if they are recognized for what they are. But at best they are makeshifts and substitutes for genuine biological statements, and the fact that recourse is had to them is surely a sign of immaturity. Science demands great linguistic austerity and discipline, and the canons of good style in scientific writing are different from those of good writing in other kinds of literature." Another argument is that "sooner or later the linguistic habits of everyday life will cease to do justice to... the... increasing complexity and novelty of observation and hypothesis." A third argument is that scientific language is used not only for the purpose of communication, for recording observations, or for formulating general laws or hypotheses. It is also used for calculation and the unearthing of the consequences of our assumptions. The logic underlying a formalized language is explicitly designed to enable us to calculate easily and efficiently. The important, and now thoroughly established, methodological distinction between object-language and meta-language is blurred for natural language and is best maintained in terms of formalized language-systems. And, finally, in natural language the important distinction between syntax and semantics also tends to be blurred. "From both the syntactical and the semantical points of view natural languages are incredibly complicated and unruly. The rules of ordinary gram mar are quite insufficient from the standpoint of the requirements of science, and the problems connected with meaning and truth in relation to natural languages are enormously complicated and perhaps insoluble.". (shrink)