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)

Although a large literature demonstrates that object‐extracted relative clauses (ORCs) are harder to process than subject‐extracted relative clauses (SRCs), there is less agreement regarding where during processing this difficulty emerges, as well as how best to explain these effects. An eye‐tracking study by Staub, Dillon, and Clifton (2017) demonstrated that readers experience more processing difficulty at the matrix verb for ORCs than for SRCs when the matrix verb immediately follows the relative clause (RC), but the difficulty is eliminated if a (...) prepositional phrase (PP) intervenes. A careful examination of Staub et al.’s materials reveals that the types of PPs used in the experiment were a mixture of locative and temporal PPs. This is important in that locative PPs can modify either a noun phrase or a verb phrase (VP), whereas temporal PPs typically modify VPs, resulting in systematic differences in PP attachment across ORCs versus SRCs. In the current eye‐tracking experiment, we systematically manipulated RC type and PP type in the same sentences used by Staub et al. The manipulation of PP type resulted in a crossover pattern at the matrix verb such that there was a trend for reading times to be longer for ORCs than SRCs when the PP was locative, but reading times were longer for SRCs than ORCs when the PP was temporal. These results provide important information regarding the locus of RC‐processing effects and highlight the importance of carefully considering how intervening material might unintentionally alter the structure or the meaning of a sentence. (shrink)

With this issue we initiate the policy of expanding the scope of Tulane Studies in Philosophy to include, in addition to the work of members of the department, contributions from philosophers who have earned advanced degrees from Tulane and who are now teaching in other colleges and universities. The Editor THE LOGIC OF OUR LANGUAGE ROBERT L. ARRINGTON Wittgenstein wrote in the Tractatus that "logic is not a body of doctrine, but a mirror-image of the world. " 1 In line (...) with his suggestion that a proposition is a 'picture', Wittgenstein argued that propositions 'show' the logical structure of the real. He was insistent, however, that "the apparent logical form of a proposition need not be its real one. " 2 As a result of this we can misunderstand the structure of fact. Philosophical problems arise just when "the logic of our language is mis understood. " 3 It is common knowledge that much of this view of logic was rejected by Wittgenstein himself in the Philosophical Investi gations. There we are told that language has no ideal or sublime 4 logic which mirrors the structure of the extra-linguistic world. Consequently, inferences from the structure of language to the structure of that extra-linguistic world are invalid. Reality can be 'cut up' in any of a number of ways by language. Wittgenstein adopted a view of philosophy which would render that discipline a non-explanatory, non-critical study of the multiple ways in which language can be used. (shrink)

This book is a collection of secondary essays on America's most important philosophic thinkers—statesmen, judges, writers, educators, and activists—from the colonial period to the present. Each essay is a comprehensive introduction to the thought of a noted American on the fundamental meaning of the American regime.

In the conclusion to this multi-part article I first review the discussions carried out around the six essential questions in psychiatric diagnosis – the position taken by Allen Frances on each question, the commentaries on the respective question along with Frances’ responses to the commentaries, and my own view of the multiple discussions. In this review I emphasize that the core question is the first – what is the nature of psychiatric illness – and that in some manner all further (...) questions follow from the first. Following this review I attempt to move the discussion forward, addressing the first question from the perspectives of natural kind analysis and complexity analysis. This reflection leads toward a view of psychiatric disorders – and future nosologies – as far more complex and uncertain than we have imagined. (shrink)

In face of the multiple controversies surrounding the DSM process in general and the development of DSM-5 in particular, we have organized a discussion around what we consider six essential questions in further work on the DSM. The six questions involve: 1) the nature of a mental disorder; 2) the definition of mental disorder; 3) the issue of whether, in the current state of psychiatric science, DSM-5 should assume a cautious, conservative posture or an assertive, transformative posture; 4) the role (...) of pragmatic considerations in the construction of DSM-5; 5) the issue of utility of the DSM - whether DSM-III and IV have been designed more for clinicians or researchers, and how this conflict should be dealt with in the new manual; and 6) the possibility and advisability, given all the problems with DSM-III and IV, of designing a different diagnostic system. Part I of this article will take up the first two questions. With the first question, invited commentators express a range of opinion regarding the nature of psychiatric disorders, loosely divided into a realist position that the diagnostic categories represent real diseases that we can accurately name and know with our perceptual abilities, a middle, nominalist position that psychiatric disorders do exist in the real world but that our diagnostic categories are constructs that may or may not accurately represent the disorders out there, and finally a purely constructivist position that the diagnostic categories are simply constructs with no evidence of psychiatric disorders in the real world. The second question again offers a range of opinion as to how we should define a mental or psychiatric disorder, including the possibility that we should not try to formulate a definition. The general introduction, as well as the introductions and conclusions for the specific questions, are written by James Phillips, and the responses to commentaries are written by Allen Frances. (shrink)

In face of the multiple controversies surrounding the DSM process in general and the development of DSM-5 in particular, we have organized a discussion around what we consider six essential questions in further work on the DSM. The six questions involve: 1) the nature of a mental disorder; 2) the definition of mental disorder; 3) the issue of whether, in the current state of psychiatric science, DSM-5 should assume a cautious, conservative posture or an assertive, transformative posture; 4) the role (...) of pragmatic considerations in the construction of DSM-5; 5) the issue of utility of the DSM - whether DSM-III and IV have been designed more for clinicians or researchers, and how this conflict should be dealt with in the new manual; and 6) the possibility and advisability, given all the problems with DSM-III and IV, of designing a different diagnostic system. Part I of this article took up the first two questions. Part II will take up the second two questions. Question 3 deals with the question as to whether DSM-V should assume a conservative or assertive posture in making changes from DSM-IV. That question in turn breaks down into discussion of diagnoses that depend on, and aim toward, empirical, scientific validation, and diagnoses that are more value-laden and less amenable to scientific validation. Question 4 takes up the role of pragmatic consideration in a psychiatric nosology, whether the purely empirical considerations need to be tempered by considerations of practical consequence. As in Part 1 of this article, the general introduction, as well as the introductions and conclusions for the specific questions, are written by James Phillips, and the responses to commentaries are written by Allen Frances. (shrink)

In face of the multiple controversies surrounding the DSM process in general and the development of DSM-5 in particular, we have organized a discussion around what we consider six essential questions in further work on the DSM. The six questions involve: 1) the nature of a mental disorder; 2) the definition of mental disorder; 3) the issue of whether, in the current state of psychiatric science, DSM-5 should assume a cautious, conservative posture or an assertive, transformative posture; 4) the role (...) of pragmatic considerations in the construction of DSM-5; 5) the issue of utility of the DSM – whether DSM-III and IV have been designed more for clinicians or researchers, and how this conflict should be dealt with in the new manual; and 6) the possibility and advisability, given all the problems with DSM-III and IV, of designing a different diagnostic system. Part 1 of this article took up the first two questions. Part 2 took up the second two questions. Part 3 now deals with Questions 5 & 6. Question 5 confronts the issue of utility, whether the manual design of DSM-III and IV favors clinicians or researchers, and what that means for DSM-5. Our final question, Question 6, takes up a concluding issue, whether the acknowledged problems with the earlier DSMs warrants a significant overhaul of DSM-5 and future manuals. As in Parts 1 & 2 of this article, the general introduction, as well as the introductions and conclusions for the specific questions, are written by James Phillips, and the responses to commentaries are written by Allen Frances. (shrink)

Introduction, W G Runciman Social Evolution in Primates: The Role of Ecological Factors and Male Behaviour, Carel P van Schaik Determinants of Group Size in Primates: A General Model, R I M Dunbar Function and Intention in the Calls of Non-Human Primates, Dorothy L Cheney & Robert M Seyfarth Why Culture is Common, but Cultural Evolution is Rare, Robert Boyd & Peter J Richerson An Evolutionary and Chronological Framework for Human Social Behaviour, Robert A Foley Friendship and the Banker?s (...) Paradox: Other Pathways to the Evolution of Adaptations for Altruism, John Tooby & Leda Cosmides The Early Prehistory of Human Social Behaviour: Issues of Archaeological Inference and Cognitive Evolution, Steven Mithen The Emergence of Biologically Modern Populations in Europe: A Social and Cognitive ?Revolution??, Paul Mellars Responses to Environmental Novelty: Changes in Men?s Marriage Strategies in a Rural Kenyan Community, Monique Borgerhoff Mulder Genetic Language Impairment: Unruly Grammars, M Gopnik, J Dalalakis, S E Fukuda, S Fukuda & E Kehayia The Emergence of Cultures among Wild Chimpanzees, Christophe Boesch Terrestriality, Bipedalism and the Origin of Language, Leslie C Aiello Conclusions, John Maynard Smith. (shrink)

Over 150 years have elapsed since Hegel lectured on the philosophy of religion in Berlin. Now for the first time a critical edition of the fragmentary manuscript that he used to lecture in 1821 has been published in a masive volume, to be followed by subsequent volumes of equal size containing student notes or transcripts of the 1824 and 1827 lectures. Despite heroic efforts by the editor, Karl-Heinz Ilting of Saarbrucken, who previously edited Hegel’s lectures on the philosophy of right (...) according to the same principles, this new edition is unsatisfactory on several counts, and we shall have to await the appearance of these texts in the Gesammelte Werke slowly being produced by the Hegel-Archiv at the Ruhr-Universität in Bochum before we have a completely adequate critical edition of Hegel’s philosophy of religion lectures. (shrink)

Peter Abelard (1079–1142 ce) was the most wide‐ranging philosopher of the twelfth century. He quickly established himself as a leading teacher of logic in and near Paris shortly after 1100. After his affair with Heloise, and his subsequent castration, Abelard became a monk, but he returned to teaching in the Paris schools until 1140, when his work was condemned by a Church Council at Sens. His logical writings were based around discussion of the “Old Logic”: Porphyry's Isagoge, aristotle'S Categories (...) and On Interpretation and boethius'S textbook on topical inference. They comprise a freestanding Dialectica (“Logic”; probably c.1116), a set of commentaries (known as the Logica [Ingredientibus], c. 1119) and a later (c. 1125) commentary on the Isagoge (Logica Nostrorum Petititoni Sociorum or Glossulae). In a work Abelard called his Theologia, issued in three main versions (between 1120 and c.1134), he attempted a logical analysis of trinitarian relations and explored the philosophical problems surrounding God's claims to omnipotence and omniscience. The Collationes (“Debates,” also known as “Dialogue between a Christian, a Philosopher and a Jew”; probably c.1130) present a rational investigation into the nature of the highest good, in which the Christian and the Philosopher (who seems to be modeled on a philosopher of pagan antiquity) are remarkably in agreement. The unfinished Scito teipsum (“Know thyself,” also known as the “Ethics”; c.1138) analyses moral action. (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)

Given its non-invasive nature, there is increasing interest in the use of transcutaneous vagus nerve stimulation across basic, translational and clinical research. Contemporaneously, tVNS can be achieved by stimulating either the auricular branch or the cervical bundle of the vagus nerve, referred to as transcutaneous auricular vagus nerve stimulation and transcutaneous cervical VNS, respectively. In order to advance the field in a systematic manner, studies using these technologies need to adequately report sufficient methodological detail to enable comparison of results between (...) studies, replication of studies, as well as enhancing study participant safety. We systematically reviewed the existing tVNS literature to evaluate current reporting practices. Based on this review, and consensus among participating authors, we propose a set of minimal reporting items to guide future tVNS studies. The suggested items address specific technical aspects of the device and stimulation parameters. We also cover general recommendations including inclusion and exclusion criteria for participants, outcome parameters and the detailed reporting of side effects. Furthermore, we review strategies used to identify the optimal stimulation parameters for a given research setting and summarize ongoing developments in animal research with potential implications for the application of tVNS in humans. Finally, we discuss the potential of tVNS in future research as well as the associated challenges across several disciplines in research and clinical practice. (shrink)

Given its non-invasive nature, there is increasing interest in the use of transcutaneous vagus nerve stimulation across basic, translational and clinical research. Contemporaneously, tVNS can be achieved by stimulating either the auricular branch or the cervical bundle of the vagus nerve, referred to as transcutaneous auricular vagus nerve stimulation and transcutaneous cervical VNS, respectively. In order to advance the field in a systematic manner, studies using these technologies need to adequately report sufficient methodological detail to enable comparison of results between (...) studies, replication of studies, as well as enhancing study participant safety. We systematically reviewed the existing tVNS literature to evaluate current reporting practices. Based on this review, and consensus among participating authors, we propose a set of minimal reporting items to guide future tVNS studies. The suggested items address specific technical aspects of the device and stimulation parameters. We also cover general recommendations including inclusion and exclusion criteria for participants, outcome parameters and the detailed reporting of side effects. Furthermore, we review strategies used to identify the optimal stimulation parameters for a given research setting and summarize ongoing developments in animal research with potential implications for the application of tVNS in humans. Finally, we discuss the potential of tVNS in future research as well as the associated challenges across several disciplines in research and clinical practice. (shrink)

About one third of patients with epilepsy have seizures refractory to the medical treatment. Electrical stimulation mapping is the gold standard for the identification of “eloquent” areas prior to resection of epileptogenic tissue. However, it is time-consuming and may cause undesired side effects. Broadband gamma activity recorded with extraoperative electrocorticography during cognitive tasks may be an alternative to ESM but until now has not proven of definitive clinical value. Considering their role in cognition, the alpha and beta bands could further (...) improve the identification of eloquent cortex. We compared gamma, alpha and beta activity, and their combinations for the identification of eloquent cortical areas defined by ESM. Ten patients with intractable focal epilepsy participated in a delayed-match-to-sample task, where syllable sounds were compared to visually presented letters. We used a generalized linear model approach to find the optimal weighting of each band for predicting ESM-defined categories and estimated the diagnostic ability by calculating the area under the receiver operating characteristic curve. Gamma activity increased more in eloquent than in non-eloquent areas, whereas alpha and beta power decreased more in eloquent areas. Diagnostic ability of each band was close to 0.7 for all bands but depended on multiple factors including the time period of the cognitive task, the location of the electrodes and the patient’s degree of attention to the stimulus. We show that diagnostic ability can be increased by 3–5% by combining gamma and alpha and by 7.5–11% when gamma and beta were combined. We then show how ECoG power modulation from cognitive testing can be used to map the probability of eloquence in individual patients and how this probability map can be used in clinical settings to optimize ESM planning. We conclude that the combination of gamma and beta power modulation during cognitive testing can contribute to the identification of eloquent areas prior to ESM in patients with refractory focal epilepsy. (shrink)

In his theoretical philosophy, Immanuel Kant argues that experience comes from two sources that are radically different but equally necessary: the rule-governed activity of thinking and the givenness of sensations. He supposes that both could be traced to some common root but concludes that whatever it is, is in principle unknowable. Kant's idealist successors, J.G. Fichte and F.W.J. Schelling, each attempt to provide a unified account of experience by identifying the ultimate basis of subject and object—Fichte by referring to the (...) I's activity and Schelling by referring to the Absolute. Because we can know only appearances, an implication of Kant's transcendental inquiry, Fichte and Schelling have difficulty... (shrink)

This article is part of a For-Discussion-Section of Methods of Information in Medicine about the paper "Biomedical Informatics: We Are What We Publish", written by Peter L. Elkin, Steven H. Brown, and Graham Wright. It is introduced by an editorial. This article contains the combined commentaries invited to independently comment on the Elkin et al. paper. In subsequent issues the discussion can continue through letters to the editor.