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)

We generalize two well-known model-theoretic characterization theorems from propositional modal logic to first-order modal logic. We first study FML-definable frames and give a version of the Goldblatt–Thomason theorem for this logic. The advantage of this result, compared with the original Goldblatt–Thomason theorem, is that it does not need the condition of ultrafilter reflection and uses only closure under bounded morphic images, generated subframes and disjoint unions. We then investigate Lindström type theorems for first-order modal logic. We show that FML has (...) the maximal expressive power among the logics extending FML which satisfy compactness, bisimulation invariance and the Tarski union property. (shrink)

ARISTOTLE'S PROGRAM Aristotle says outright that the law of non-contradiction cannot be demonstrated: you can't prove everything, and among the things you ...

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)

Looking at the early work in the philosophy of conspiracy theory theory, I put in context the papers in this special issue on new work on conspiracy theory theory (itself the product of the 1st International Conference on the Philosophy of Conspiracy Theory held in February 2022), showing how this new generation of work not only grew out of, but is itself a novel extension of the first generation of philosophical interest in these things called ‘conspiracy theories’.

This reply to an ongoing debate between conspiracy theory researchers from different disciplines exposes the conceptual confusions that underlie some of the disagreements in conspiracy theory research. Reconciling these conceptual confusions is important because conspiracy theories are a multidisciplinary topic and a profound understanding of them requires integrative insights from different fields. Specifically, we distinguish research focussing on conspiracy *theories* (and theorizing) from research of conspiracy *belief* (and mindset, theorists) and explain how particularism with regards to conspiracy theories does not (...) mean we cannot define a problematic subclass of conspiracy beliefs, while avoiding the problems of generalism. We hope this reply helps conspiracy theory researchers recognize the differences between studying conspiracy theories and conspiracy beliefs and appreciate the possibilities for fruitful, integrative, and interdisciplinary research. (shrink)

Two and a half thousand years ago Greek philosophers "looked up at the sky and formed a theory of everything." Though their solutions are little credited today, the questions remain fresh. Early Greek thinkers struggled to come to terms with and explain the totality of their surroundings, to identitify an original substance from which the universe was compounded, and to reconcile the presence of balance and proportion with the apparent disorder of the cosmos. M. R. Wright examines cosmological theories of (...) the "natural philosophers" from Thales, Anaximander and Anaximenes to Plato, the Stoics and the NeoPlatonists. The importance of Babylonian and Egyptian forerunners is also emphasized. Cosmology in Antiquity is a comprehensive introduction to the cosmological thought in ancient times. (shrink)

An analysis of Mark Bevir's account of the role of language and tradition on the one hand, and the individual on the other in the generation of ideas, and proposal of an alternative account It endorses Bevir's project of finding a middle way between individualism and collectivism, but finds that Bevir exaggerates the role of the individual. It argues that human selves always remains dependent on language even to articulate their own intentions to themselves. Whilst they have a capacity to (...) create new linguistic expressions, this is always limited to the exploration of possibilities already latent in the language. However, no one is a mere recipient and conduit of a given language: everyone hands it on transformed by their unique appropriation of it. The antifoundationalist analyses of Wittgenstein, Newman Collingwood, and Neurath are invoked to argue that this state of affairs also applies to the individual's relation to the beliefs and values inherited traditionally: there is no possibility of a wholesale rejection of what is received; no individual can reject all received traditions, and erect an entire belief structure from scratch, but can only modify it on a piecemeal basis, so that received tradition always remains constitutive of the individual mind. It is also argued that human self-consciousness is always socially formed, and no person ever completely integrated, and stabilized. No one is ever therefore in a state of complete self-possession. One therefore must reject Bevir's claim that the historian of ideas must initially presume that individuals are sincere, conscious and rational in their expressed beliefs: ‘sincere’ self-consciousness is an ideal never fully achieved, and beliefs as to what constitutes ‘rationality’ are so varied that specific presumptions cannot be made. (shrink)