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 study, we developed and validated an instrument that researchers can use to measure the collective effort of principals and teachers who excise their own unique leadership to genera...

Gene therapy approaches have great promise in the treatment of neurodegenerative disorders and malignant brain tumors. Neuwelt et al. review available viral-mediated gene therapy methods and their blood-brain-barrier (BBB) disruption delivery technique, briefly mentioning nonviral mediated gene therapy methods. This commentary discussed the BBB disruption delivery technique, viral and nonviral mediated gene therapy approaches to Parkinson's disease, and the potential use of antisense oligo to suppress malignant brain tumors.

Urban contexts are widely conceived as inherently violent due to their putatively disorderly nature. Such a conception of violence effectively conceives it as singular and fundamentally destructive, neither of which necessarily hold universally true. Drawing on Benjamin’s ‘Critique of Violence’ and the life history of Bismarck, a former gang member turned drug dealer turned property entrepreneur living in a poor neighbourhood in Managua, Nicaragua, this article highlights how different forms of urban violence interrelate with each other over time, and how (...) they shape an individual’s urban experience and environment. In doing so, it underscores how urban violence is not a singular phenomenon, how it intertwines with a range of urban social processes, and how it is often socially constitutive rather than destructive. Seen from this perspective, the key question to ask is less to what extent violence is a hallmark of urban contexts but rather how different articulations of violence emerge in cities, and why it is that they can play such contrasting roles in the constitution of urban life. (shrink)

In the year 1471 a member of the Sorbonne, Guillaume Fichet, looking back on the history of what today we should call communication technology, divided it into three periods: antiquity , a subsequent period which we should identify as the Middle Ages , and a period just beginning . Just over five hundred years later an American scholar, Walter J. Ong, looking back on a longer historical span, divided it into orality, writing, printing, and electronic communications. No matter how (...) much these two figures may differ over details, they occupy a similar position: each stands at the start of a communications shift which has alerted him to changes in the past, and Ong claims explicitly that contrasts “between electronic media and print have sensitized us to the earlier contrast between writing and orality.” We do not have to go as far as Eric A. Havelock, who suggests that our new awareness can be precisely dated by a number of publications appearing in the annus mirabilis 1963 , in order to accept the general point that recent work has been stimulated by recent technology. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:OBJECTIVITY AND RELlGIOUS TRUTH: A COMPARISON OF WILFRED CANTWELL SMITH AND BERNARD LONERGAN DENNIS M. DOYLE University of Dayton Dayton, Ohio WILFRED CANTWELL SMITH •and Bernard Lonergan both propose a new agenda for theology n response to ;the same basic cultura.I developments.1 Both Smith and Lonergan pinpoint the crux of the current siturution!aJS the convergence of various cultures in a world where Western culture had.been heM by its pwrticiipants (...) to be univers•al.and normrutive. The majo'l" problem concerning religious truth :that 1 arises out of this situation concerns universality. Formulrutions tha:t were once taken for granted are now seen to he relative to their context. Concepts that it.T1anscend particular formulations are themselves recognized irus indigenous to 1a culture. T·ruth itself is questioned as to whether it too is not!l'elative to eaich oontert. The responses of Smith and Lonergan to this situa:tion are remarkably ·similar in structure. In the midst of these similarities, 1 however, arise some differences with important implications concerning oibjectivity, itruth, and theology in a global context. Objec:tivity, Method, and Human Knowledge Smith and Lonergan both 'address rthe issue of human knowing before establishing their programs for theo1 logy.2 For botih, 1 Smith's proposal is put forth in Towards a World Theology (Phila.: Westminster Press, 1981 )• Lonergan's proposal can be found in Method in Theology (N.Y.: Herder and Herder, 1972). 2 Smith's reflections on human knowing are in "Objectivity and the Humane Sciences,'' in Towards a World Theology, pp. 56·80'. Lonergan's 461 462 DENNIS M. DOYLE a major problem in wayis of conceiving human knowing in recent centuries has heen an ohjectivism according to which knowledge was iheld to he absolute without regard to human SUJbjectivity and without an openness to other cultures. Both find a £acile cultural remtivism to he.an unsatisfactory reaction to this problem. In response, :both Smith and Lonergan try to re-root human knowing in a human conte:rl. Lonergan does ·this hy establishing the ground of knowing in an analysis of human intentionality. Smith does this by estaiblishing the ground of knowing in a mutual interchange between persons who participate in some traditions and who are observers of other traditions. Smith la.bels such knowing ·a" 001·iporaite critica1 self-iconsciousness." What emerges from such consciousness is "humane knowledge." Although some major di:ffevences arise at this point, the context of istructul'lal similarities must he noted.3 For hoth Smith and Lonergan, hruman knowing is intrinsically connected with :the quality of living both individually and oommullla1ly. Eiach in his own way stresses that knowing is vitally linked to the consciousness of individuals. Each in his own way stresses that knowing takes place within ·community, and that the breadth and quality of the community affects the breadth and quality of the knowing. Smith •and Lonergan both, furthermore, envision the taisk of theology as the conceptualization and articulation in a new context of wihat was once known in a strictly objective, theoretical f:vame;work. Both, finailily, 'lay ouit the major work on human knowing is Insight: A Study of Human Understo;nding (N.Y.: Philosophical Library, 1957). For a summary view, see chapter one of Method in Theology. For Lonergan's position on objectivity, see "The Origins of Christian Realism" in A Second Collection (Phila.: Westminster Press, 1974), ·pp. 239-61. a For an earlier comparison of the methods of Smith and Lonergan, see Walter E. Conn, "'Faith' and 'Cumulative Tradition' in Functional Specialization : A Study in the Methodologies of Wilfred Cantwell Smith and Bernard Lonergan," Studies in ReligiOn/Soiences Religieuses 5 (1975/76) : 221-46•.Although this article was published before several of Smith's major works in the area, the methodological similarities unearthed by Conn still hold true. WILFRED CANTWELL SMITH & BERNARD LONERGAN 463 problem specifically in terms of tmnscending false subject/object :dichotomies. At this point, however, differences between Smith and Lonwgian begin to emerge, foir each attempts to transcend false.suibjoot/oibject dichotomies in a different way. Lonergan holds that objectivity is the fruit of authentic ;subjectivity.4 1t is intended hy the self-transcending subject who loves... (shrink)

In “Minds, Brains, and Norms,” Michael Pardo and Dennis Patterson claim that the idea that ‘you are your brain’ does not contribute to a plausible account of human behavior. I argue that they leave too little of the brain in their account of different types of behavior.

In this essay, I attempt to explore Dennis Schmidt’s pervasive claim throughout his work of a deep affinity between aesthetic experience and ethical life. In a discussion of what Schmidt calls the intensification of life, the essay shows how for Schmidt birth and death are moments that have a peculiar capacity to reveal what he calls the idiom of the ethical. At the end of the essay, I turn to Schmidt’s discussion of Greek tragedy as an exemplary site for his (...) unique sense of original ethics. (shrink)

At the invitation of the Editors, we wrote an article (entitled, “Minds, Brains, and Norms”) detailing our views on a variety of claims by those arguing for the explanatory power of neuroscience in matters of law and ethics. The Editors invited comments on our article from four distinguished academics (Walter Glannon, Carl Craver, Sarah Robins, and Thomas Nadelhoffer) and invited our reply to their critique of our views. In this reply to our commentators, we correct some potential misunderstandings of (...) our views and further clarify our positions with discussions of the conceptual-empirical distinction, rule-following, explanations at the personal and subpersonal levels, memory, and lie detection. Although we acknowledge many of the criticisms advanced by our distinguished colleagues, we conclude that, in several important respects, their criticisms confirm the points made in our original article. (shrink)

In the past decades, reductionism has dominated both research directions and funding policies in clinical psychology and psychiatry. The intense search for the biological basis of mental disorders, however, has not resulted in conclusive reductionist explanations of psychopathology. Recently, network models have been proposed as an alternative framework for the analysis of mental disorders, in which mental disorders arise from the causal interplay between symptoms. In this target article, we show that this conceptualization can help explain why reductionist approaches in (...) psychiatry and clinical psychology are on the wrong track. First, symptom networks preclude the identification of a common cause of symptomatology with a neurobiological condition; in symptom networks, there is no such common cause. Second, symptom network relations depend on the content of mental states and, as such, feature intentionality. Third, the strength of network relations is highly likely to depend partially on cultural and historical contexts as well as external mechanisms in the environment. Taken together, these properties suggest that, if mental disorders are indeed networks of causally related symptoms, reductionist accounts cannot achieve the level of success associated with reductionist disease models in modern medicine. As an alternative strategy, we propose to interpret network structures in terms of D. C. Dennett's (1987) notion ofreal patterns, and suggest that, instead of being reducible to a biological basis, mental disorders feature biological and psychological factors that are deeply intertwined in feedback loops. This suggests that neither psychological nor biological levels can claim causal or explanatory priority, and that a holistic research strategy is necessary for progress in the study of mental disorders. (shrink)

Concerns about exploiting the poor or economically disadvantaged in clinical research are widespread in the bioethics community. For some, any research that involves economically disadvantaged individuals is de facto ethically problematic. The economically disadvantaged are thought of as “venerable” to exploitation, impaired decision making, or both, thus requiring either special protections or complete exclusion from research. A closer examination of the worries about vulnerabilities among the economically disadvantaged reveals that some of these worries are empirically or logically untenable, while others (...) can be better resolved by improved study designs than by blanket exclusion of poorer individuals from research participation. The scientific objective to generate generalisable results and the ethical objective to fairly distribute both the risks and benefits of research oblige researchers not to unnecessarily bar economically disadvantaged subjects from clinical research participation. (shrink)

I explore gender messages in Boy Scout and Girl Scout handbooks through an analysis of how gender is infused in the context and content of Scout activities as well as in instructions about how the Scouts are to approach these activities. I find that girls are offered more activities intended to be performed in group contexts than are boys. Boys are offered proportionately more activities with scientific content and proportionately fewer artistic activities than are girls. The girls’ handbook conveys messages (...) about approaching activities with autonomous and critical thinking, whereas the boys’ handbook facilitates intellectual passivity through a reliance on organizational scripts. Taken together, girls’ messages promote an “up-to-date traditional woman” consistent with the Girl Scouts’ organizational roots; boys’ messages promote an assertive heteronormative masculinity that is offset by facilitating boys’ intellectual passivity. (shrink)

An effective restructuring of the social sciences around the evolutionary model requires that evolutionary theory has explanatory power with respect to the spread of cultural traits: The causal mechanisms involved should be structurally analogous to those of biological evolution. I argue that this is implausible because phenotypical consequences of cultural traits are not causally relevant to their chances of “survival.” (Published Online November 9 2006).

Since the Supreme Court upheld the partial birth abortion ban in 2007, more U.S. abortion providers have begun performing intraamniotic digoxin injections prior to uterine dilation and evacuations. These injections can cause medical harm to abortion patients. Our objective is to perform an in-depth bioethical analysis of this procedure, which is performed mainly for the provider’s legal benefit despite potential medical consequences for the patient.

Jones & Love (J&L) suggest that Bayesian approaches to the explanation of human behavior should be constrained by mechanistic theories. We argue that their proposal misconstrues the relation between process models, such as the Bayesian model, and mechanisms. While mechanistic theories can answer specific issues that arise from the study of processes, one cannot expect them to provide constraints in general.

Inadequate pain control, especially in older adults, remains a significant issue when caring for this population. Older adults, many of whom experience multiple acute and chronic conditions, are especially vulnerable to having their pain seriously underassessed and inadequately treated. Nurses have an ethical obligation to appropriately treat patients’ pain. To fulfill their ethical obligation to relieve pain in older patients, nurses often need to advocate on their behalf. This article provides an overview of the persistent problem of undertreated pain in (...) older adults and explores how nurses can meet this ethical duty through the application of Beauchamp and Childress’ three principles of beneficence. (shrink)

When it originated in the late 19th century, psychometrics was a field with both a scientific and a social mission: psychometrics provided new methods for research into individual differences, and at the same time, these psychometric instruments were considered a means to create a new social order. In contrast, contemporary psychometrics - due to its highly technical nature and its limited involvement in substantive psychological research - has created the impression of being a value-free discipline. In this article, we develop (...) a contrasting characterization of contemporary psychometrics as a value-laden discipline. We expose four such values: that individual differences are quantitative (rather than qualitative), that measurement should be objective in a specific sense, that test items should be fair, and that utility of a model is more important than its truth. Our goal is not to criticize psychometrics for employing these values, but rather to bring them into the open and to show that these values are not inevitable and are in need of systematic evaluation. (shrink)

his paper presents a unified treatment of the propositional and first-order many-valued logics through the method of tableaux. It is shown that several important results on the proof theory and model theory of those logics can be obtained in a general way. We obtain, in this direction, abstract versions of the completeness theorem, model existence theorem (using a generalization of the classical analytic consistency properties), compactness theorem and Lowenheim-Skolem theorem. The paper is completely self-contained and includes examples of application to (...) particular many-valued formal systems. (shrink)

Wollen (2022) is a critique of deontological libertarianism, the version of this philosophy predicated upon private property rights and the non-aggression principle. The launching pad for this article of his is the difficulty faced by conjoined twins, who diverge sharply in their view of their desirable future. The present rejoinder maintains that this author’s critique fails; further, that it really has little or nothing to do with conjoined twins per se, but, rather, aims at an entirely different challenge, that of (...) the tie or the dead heat. This latter is a critique that all political economic philosophies face, without exception, and libertarianism does no worse on this challenge than any other, the critique of Wollen to the contrary notwithstanding. (shrink)

OntoClean is an approach towards the formal evaluation of taxonomic relations in ontologies. The application of OntoClean consists of two main steps. First, concepts are tagged according to meta-pr...