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)

The earlier volume in this series dealt with two religions of Indian origin, namely, Buddhism and Jainism. The Indian religious scene, however, is characterized by not only religions which originated in India but also by religions which entered India from outside India and made their home here. Thus religious life in India has been enlivened throughout its history by the presence of religions of foreign origin on its soil almost from the very time they came into existence. This volume covers (...) three such religions—Zoraoastrianism, Judaism, and Islam. In the case of Zoraostianism, even its very beginnings are intertwined with India, as Zoroastrianism reformed a preexisting religion which had strong links to the Vedic heritage of India. This relationship took on a new dimension when a Zoroastrian community, fearing persecution in Persia after its Arab conquest, sought shelter in western India and ultimately went on to produce India’s pioneering nationalist in the figure of Dadabhai Naoroji ( 1825-1917), also known as the Grand Old Man of India. Jews found refuge in south India after the destruction of the Temple by the Romans in 70 C.E. and have remained a part of the Indian religious scene since then, some even returning to Israel after it was founded in 1948. Islam arrived in Kerala as soon as it was founded and one of the earliest mosques in the history of Islam is found in India. Islam differs from the previously mentioned religions inasmuch as it went on to gain political hegemony over parts of the country for considerable periods of time, which meant that its impact on the religious life of the subcontinent has been greater compared to the other religions. It has also meant that Islam has existed in a religiously plural environment in India for a longer period than elsewhere in the world so that not only has Islam left a mark on India, India has also left its mark on it. Indeed all the three religions covered in this volume share this dual feature, that they have profoundly influenced Indian religious life and have also in turn been profoundly influenced by their presence in India. (shrink)

The earlier volume in this series dealt with two religions of Indian origin, namely, Buddhism and Jainism. The Indian religious scene, however, is characterized by not only religions which originated in India but also by religions which entered India from outside India and made their home here. Thus religious life in India has been enlivened throughout its history by the presence of religions of foreign origin on its soil almost from the very time they came into existence. This volume covers (...) three such religions—Zoraoastrianism, Judaism, and Islam. In the case of Zoraostianism, even its very beginnings are intertwined with India, as Zoroastrianism reformed a preexisting religion which had strong links to the Vedic heritage of India. This relationship took on a new dimension when a Zoroastrian community, fearing persecution in Persia after its Arab conquest, sought shelter in western India and ultimately went on to produce India’s pioneering nationalist in the figure of Dadabhai Naoroji ( 1825-1917), also known as the Grand Old Man of India. Jews found refuge in south India after the destruction of the Temple by the Romans in 70 C.E. and have remained a part of the Indian religious scene since then, some even returning to Israel after it was founded in 1948. Islam arrived in Kerala as soon as it was founded and one of the earliest mosques in the history of Islam is found in India. Islam differs from the previously mentioned religions inasmuch as it went on to gain political hegemony over parts of the country for considerable periods of time, which meant that its impact on the religious life of the subcontinent has been greater compared to the other religions. It has also meant that Islam has existed in a religiously plural environment in India for a longer period than elsewhere in the world so that not only has Islam left a mark on India, India has also left its mark on it. Indeed all the three religions covered in this volume share this dual feature, that they have profoundly influenced Indian religious life and have also in turn been profoundly influenced by their presence in India. (shrink)

Introduction: The aim of this study was to investigate time-trial (TT) performance in the presence of one competitor and in a group with competitors of various abilities. Methods: In a randomized order, 24 participants performed a 5-km cycling TT individually (IND), with one similarly matched participant (1v1), and in a group of four participants (GRP). For the GRP session, two pairs of matched participants from the 1v1 session were used. Pairs were selected so that TT duration was considered either inferior (...) (INF) or superior (SUP) compared to the other pair of participants. Results: Overall, TT duration (P = 0.86, ηp2 < 0.01) was not different between conditions, whilst heart rate (HR) was significantly greater in GRP compared to IND (P < 0.01, ηp2 = 0.16). For INF, a large effect size for both mean power (P = 0.07, ηp2 = 0.15) and HR (P = 0.05, ηp2 = 0.16), indicates greatest effort in GRP. Pacing behaviour was affected by competition but similar in 1v1 and GRP for SUP, whilst large effect sizes indicate an increased power output in the initial 750-m for INF in GRP. Additionally, for INF, there was a significant correlation with ego orientation for an increase in TT duration between the GRP session and both the IND (r = 0.43, P = 0.04) and 1v1 (r = 0.54, P = 0.01) sessions. Conclusion: For INF participants, intensity was increased when competing in GRP. Yet, the presence of the SUP competitors resulted in lesser performance improvements for ego oriented INF participants. These findings demonstrate that consideration should be given to the ability of competitors in a group setting to provide adequate motivation. (shrink)

One hypothesis concerning the human dorsal anterior cingulate cortex (ACC) is that it functions, in part, to signal the occurrence of conflicts in information processing, thereby triggering compensatory adjustments in cognitive control. Since this idea was first proposed, a great deal of relevant empirical evidence has accrued. This evidence has largely corroborated the conflict-monitoring hypothesis, and some very recent work has provided striking new support for the theory. At the same time, other findings have posed specific challenges, especially concerning the (...) way the theory addresses the processing of errors. Recent research has also begun to shed light on the larger function of the ACC, suggesting some new possibilities concerning how conflict monitoring might fit into the cingulate's overall role in cognition and action. (shrink)

The global pandemic needs to mark a turning point for the peoples of Aotearoa New Zealand. How can we make sure that our culturally diverse nation charts an equitable and sustainable path through and beyond this new world? In a less affluent future, how can we ensure that all New Zealanders have fair access to opportunities? One challenge is to preserve the sense of common purpose so critical to protecting each other in the face of Covid-19. How can we centre (...) what we have learnt about resilience within Māori and wider Pacific communities in our reforms? How can public understanding of Covid-19 science create a platform for the future social valuing of expertise? How can we ensure that the impact of Covid-19 in New Zealand results in a more sustainable, and inclusive workforce–for instance by expanding our perceptions of the value of our workers through promoting digital inclusion? To meet these challenges, we must reimagine our existing traditions of thought, breathing new life into perennial concepts and debates. Our paper indicates some of the ways that Philosophy is central to this collective reimagining, highlighting solutions to be found across our rich philosophical traditions. (shrink)

Cognitive control has long been one of the most active areas of computational modeling work in cognitive science. The focus on computational models as a medium for specifying and developing theory predates the PDP books, and cognitive control was not one of the areas on which they focused. However, the framework they provided has injected work on cognitive control with new energy and new ideas. On the occasion of the books' anniversary, we review computational modeling in the study of cognitive (...) control, with a focus on the influence that the PDP approach has brought to bear in this area. Rather than providing a comprehensive review, we offer a framework for thinking about past and future modeling efforts in this domain. We define control in terms of the optimal parameterization of task processing. From this vantage point, the development of control systems in the brain can be seen as responding to the structure of naturalistic tasks, through the filter of the brain systems with which control directly interfaces. This perspective lays open a set of fascinating but difficult research questions, which together define an important frontier for future computational research. (shrink)

Although a great deal of literature has looked at how individuals respond to stigma, far less has been written about how professional groups address challenges to their self-perception as abiding by clear moral standards. In this paper, we ask how professional group members maintain a positive self-perception in the face of moral stigma. Drawing on pragmatic and cultural sociology, we claim that professional communities hold narratives that link various aspects of the work their members perform with specific understanding of the (...) common good. These narratives allow professionals to maintain a shared view of their work as benefitting society and to perceive themselves as moral individuals. As a case study, we focus on the advertising industry, which has long been stigmatized as complicit in exploitative capitalist mechanisms and cultural degradation. We draw on nine total months of fieldwork and seventy-four interviews across three US advertising agencies. We find that advertising practitioners use narratives to present their work as contributing to the common good, depicting themselves as moral individuals who care about others in the process. We analyze three prevalent narratives: the account-driven narrative, which links moral virtue to caring for clients; the creative-driven narrative, which ties caring to the production of meaningful advertisements; and the strategic-driven narrative, which sees caring in finding meaningful relationships for consumers and brands. (shrink)

Despite having international and national legislative frameworks and policies that guarantee children’s rights and encourage their participation in matters affecting them, consulting children has received scant scholarly attention in the African context. Notwithstanding this state of affairs, it is important to ask whether, in keeping with growing progressive practices, having children as active researchers is a feasible goal to achieve and, if so, how might this be possible. Drawing on Swartz and Nyamnjoh’s framework of research existing along an emancipatory continuum, (...) we argue for practical, methodological interventions to bridge the researcher–researched divide. We show, using four case studies, how giving children a voice – a key feature of emancipatory research – as participants in educational research has the potential to afford them space to co-enact the research and develop their sense of agency. The four case studies were drawn from investigations of lived experiences of orphaned children and conceptions of education quality in South Africa; consulting children about sex and HIV/AIDS education in South Africa, Tanzania and Kenya; a study of a community-based peer education programme in South Africa and language and mathematics skills assessments in a large-scale study. Within each case, we evaluate the extent to which the research methods used aims for and achieves children’s participation and emancipation and offer ways to overcome challenges for adopting emancipatory approaches in the schooling sector from ethical, policy and political perspectives. The article concludes with recommendations for implementing emancipatory methodologies in educational research involving children. (shrink)

The potential to instrumentalize drug use based upon the detection of very many different drug states undoubtedly exists, and such states may play a role in psychiatric and many other drug uses. Nevertheless, nonaddictive drug use is potentially more parsimoniously explained in terms of sensation seeking/impulsivity and drug expectations. Cultural factors also play a major role in nonaddictive drug use.

Medical care of critically ill and injured infants and children globally should be based on best research evidence to ensure safe, efficacious treatment. In South Africa and other low and middle-income countries, research is needed to optimise care and ensure rational, equitable allocation of scare paediatric critical care resources.

The focus of this study was to analyze the content, distribution, and comparative genome relationships of 996 chromosome bin-mapped expressed sequence tags accounting for 2266 restriction fragments on the homoeologous group 3 chromosomes of hexaploid wheat. Of these loci, 634, 884, and 748 were mapped on chromosomes 3A, 3B, and 3D, respectively. The individual chromosome bin maps revealed bins with a high density of mapped ESTs in the distal region and bins of low density in the proximal region of the (...) chromosome arms, with the exception of 3DS and 3DL. These distributions were more localized on the higher-resolution group 3 consensus map with intermediate regions of high-mapped-EST density on both chromosome arms. Gene ontology classification of mapped ESTs was not significantly different for homoeologous group 3 chromosomes compared to the other groups. A combined analysis of the individual bin maps using 537 of the mapped ESTs revealed rearrangements between the group 3 chromosomes. Approximately 232 of the consensus mapped ESTs matched sequences on rice chromosome 1 and revealed large- and small-scale differences in gene order. Of the group 3 mapped EST unigenes ∼21 and 32% matched the Arabidopsis coding regions and proteins, respectively, but no chromosome-level gene order conservation was detected. (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)

Nearly one-quarter of Costa Rica's export earnings derive from an expanding tourist sector, one that is increasingly diversified in a mix of tourist niches. Ecotourism is the fastest growing niche and its promises are featured in a range of sites and practices, including the largest multinational hospitality and hotel corporations. These companies promote a vision of sustainability that relies on expanding consumption of ‘environmental' amenities through profit-driven global corporations – a vision that is, to some, antithetical to the very meaning (...) of ecotourism. Our study explores the historical evolution of tourist development in Costa Rica, specifically large-scale coastal development, as a means for national development. Amid pressures to attract foreign direct investment in a neoliberal era, Costa Rica has struggled to maintain its developmentalism, which includes social welfare, environmental protection, and public goods, including coastal preservation and public access. We argue Costa Rica's simult.. (shrink)

Human moral judgement may have evolved to maximize the individual's welfare given parochial culturally constructed moral systems. If so, then moral condemnation should be more severe when transgressions are recent and local, and should be sensitive to the pronouncements of authority figures (who are often arbiters of moral norms), as the fitness pay-offs of moral disapproval will primarily derive from the ramifications of condemning actions that occur within the immediate social arena. Correspondingly, moral transgressions should be viewed as less objectionable (...) if they occur in other places or times, or if local authorities deem them acceptable. These predictions contrast markedly with those derived from prevailing non-evolutionary perspectives on moral judgement. Both classes of theories predict purportedly species-typical patterns, yet to our knowledge, no study to date has investigated moral judgement across a diverse set of societies, including a range of small-scale communities that differ substantially from large highly urbanized nations. We tested these predictions in five small-scale societies and two large-scale societies, finding substantial evidence of moral parochialism and contextual contingency in adults' moral judgements. Results reveal an overarching pattern in which moral condemnation reflects a concern with immediate local considerations, a pattern consistent with a variety of evolutionary accounts of moral judgement. (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)

The processes mediating dynamic and flexible responding to rapidly changing task-environments are not well understood. In the present research we employ a Stroop procedure to clarify the contribution of context-sensitive control processes to online performance. In prior work Stroop interference varied as a function of probe location context, with larger Stroop interference occurring for contexts associated with a high proportion of congruent items [Crump, M. J., Gong, Z., & Milliken, B. . The context-specific proportion congruent stroop effect: location as a (...) contextual cue. Psychonomic Bulletin & Review, 13, 316–321.] Here, we demonstrate that this effect does not depend on awareness of the context manipulation, but that it can depend on attention to the predictive context dimension, and on the relative salience of the target and predictive context dimensions. We discuss the implications of our results for current theories of cognitive control. (shrink)

Everyone is talking about food. Chefs are celebrities. "Locavore" and "freegan" have earned spots in the dictionary. Popular books and films about food production and consumption are exposing the unintended consequences of the standard American diet. Questions about the principles and values that ought to guide decisions about dinner have become urgent for moral, ecological, and health-related reasons. In _Philosophy Comes to Dinner_, twelve philosophers—some leading voices, some inspiring new ones—join the conversation, and consider issues ranging from the sustainability of (...) modern agriculture, to consumer complicity in animal exploitation, to the pros and cons of alternative diets. (shrink)

The effect of recent experience on current behavior has been studied extensively in simple laboratory tasks. We explore the nature of sequential effects in the more naturalistic setting of automobile driving. Driving is a safety-critical task in which delayed response times may have severe consequences. Using a realistic driving simulator, we find significant sequential effects in pedal-press response times that depend on the history of recent stimuli and responses. Response times are slowed up to 100 ms in particular cases, a (...) delay that has dangerous practical consequences. Further, we observe a significant number of history-related pedal misapplications, which have recently been noted as a cause for concern in the automotive safety community. By anticipating these consequences of sequential context, driver assistance systems could mitigate the effects of performance degradations and thus critically improve driver safety. (shrink)

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 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)