Progressive supranuclear palsy is a movement disorder with prominent tau neuropathology. Brain diseases with abnormal tau deposits are called tauopathies, the most common of which is Alzheimer's disease. Environmental causes of tauopathies include repetitive head trauma associated with some sports. To identify common genetic variation contributing to risk for tauopathies, we carried out a genome-wide association study of 1,114 individuals with PSP and 3,247 controls followed by a second stage in which we genotyped 1,051 cases and 3,560 controls for the (...) stage 1 SNPs that yielded P ≤ 10-3. We found significant previously unidentified signals associated with PSP risk at STX6, EIF2AK3 and MOBP. We confirmed two independent variants in MAPT affecting risk for PSP, one of which influences MAPT brain expression. The genes implicated encode proteins for vesicle-membrane fusion at the Golgi-endosomal interface, for the endoplasmic reticulum unfolded protein response and for a myelin structural component. © 2011 Nature America, Inc. All rights reserved. (shrink)

In this article we describe our approach to understanding wrongdoing in medical research and practice, which involves the statistical analysis of coded data from a large set of published cases. We focus on understanding the environmental factors that predict the kind and the severity of wrongdoing in medicine. Through review of empirical and theoretical literature, consultation with experts, the application of criminological theory, and ongoing analysis of our first 60 cases, we hypothesize that 10 contextual features of the medical environment (...) (including financial rewards, oversight failures, and patients belonging to vulnerable groups) may contribute to professional wrongdoing. We define each variable, examine data supporting our hypothesis, and present a brief case synopsis from our study that illustrates the potential influence of the variable. Finally, we discuss limitations of the resulting framework and directions for future research. (shrink)

Executive function (EF) and language learning play a prominent role in early childhood development. Empirical research continues to point to a concurrent relation between these two faculties. What has been given little attention, however, is the association between EF and speech articulation abilities in children. This study investigated this relation in children aged 4–6 years. Significant correlations indicated that children with better EF [via parental report of the Behavior Rating Inventory of Executive Function (BRIEF) inventory] exhibited stronger speech sound production (...) abilities in the articulation of the “s” and “sh” sounds. Furthermore, regression analyses revealed that the Global Executive Composite (GEC) of EF as measured by the BRIEF, served as a predictor for speech sound proficiency and that speech sound proficiency served as a predictor for the GEC. Together, these results demonstrate the imbricated nature of EF and speech sound production while bearing theoretical and practical implications. From a theoretical standpoint, the close link between EF and speech articulation may indicate a common ontogenetic pathway. From a practical perspective, the results suggest that children with speech difficulties could be at higher risk for EF deficits. (shrink)

Scholars of Plato are divided between those who emphasize the literature of the dialogues and those who emphasize the argument of the dialogues, and between those who see a development in the thought of the dialogues and those who do not. In this important book Russell Dancy focuses on the arguments and defends a developmental picture. He explains the Theory of Forms of the Phaedo and Symposium as an outgrowth of the quest for definitions canvassed in the Socratic dialogues, by (...) constructing a Theory of Definition for the Socratic dialogues based on the refutations of definitions in those dialogues, and showing how that theory is mirrored in the Theory of Forms. His discussion, notable for both its clarity and its meticulous scholarship, ranges in detail over a number of Plato's early and middle dialogues, and will be of interest to readers in Plato studies and in ancient philosophy more generally. (shrink)

Through consideration of another practical case, this chapter opens the way to a generalization of the method of argument outlined previously. Multilateral cases raise the question of how the interests of all parties can be resolved into a determinate moral conclusion, which brings the discussion to a standpoint that has affinities with classical utilitarianism. Like the principle of universalizability, the form of the utilitarian principle espoused is purely logical. In both cases, the moral substance comes from fleshing out the parties’ (...) actual inclinations and interests. The chapter embarks on a short survey of the challenges faced by a utilitarian system of this kind, before considering the concept of happiness, act‐utilitarianism, and rule‐utilitarianism. (shrink)

Originally published in 1958. A study in the logical foundations of modern theoretical semantics, this book is concerned with notions of designation and consistency as well as denotation and truth. It presents several semantical theories, each of which with what were new concepts or treatments from the author. Talking at a time when semantical theory was gained great ground, this book also looks at the methodology of the sciences and the semantics of scientific language alongside analysis of meaning and expression. (...) It is influenced by the writings of Carnap, Church, Frege, Goodman, Quine, Russell and Tarski. (shrink)

MY AIM in writing this paper is to ask help in the laying of a pair of ghosts who continue to haunt moral philosophy. Their names are ‘objectivism’ and ’subjectivism'; but the second sometimes assumes the name of ‘relativism'. I have long been convinced that the supposed battles between these two have no real substance; but for all that, they go on confusing many moral philosophers. It would be a great benefit to our profession if somebody could put an end (...) to the confusion once for all; but it has proved harder than might have been hoped, and that is my excuse for trying again. (shrink)