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 his paper, ‘Twin pregnancy, fetal reduction and the ‘all or nothing problem’, Räsänen sets out to apply Horton’s ‘all or nothing’ problem to the ethics of multifetal pregnancy reduction from a twin to a singleton pregnancy. Horton’s problem involves the following scenario: imagine that two children are about to be crushed by a collapsing building. An observer would have three options: do nothing, save one child by allowing their arms to be crushed, or save both by allowing their (...) arms to be crushed. Horton offers two intuitively plausible claims: it is morally permissible not to save either child and it is morally impermissible to save only one of the children, which taken together lead to the problematic conclusion that if an observer does not save both children, then it is better to save neither than save only one. Räsänen applies this problem to the case of 2-to-1 MFPR, arguing ultimately that, in cases where there is no medical reason to reduce, the woman ought to bring both fetuses to term. We will argue that Räsänen does not provide adequate support for the claim, crucial to his argument, that aborting only one of the fetuses in a twin pregnancy is wrong, so the ‘all or nothing’ problem does not arise in this context. Furthermore, we argue that the scenario Räsänen presents is highly unrealistic because of the clinical realities of 2-to-1 MFPR, making his argument of limited use for real-life decision making in this area. (shrink)

Background and objectives: Physicians are exposed to matters of existential character at work, but little is known about the personal impact of such issues. Methods: To explore how physicians experience and cope with existential aspects of their clinical work and how such experiences affect their professional identities, a qualitative study using individual semistructured interviews has analysed accounts of their experiences related to coping with such challenges. Analysis was by systematic text condensation. The purposeful sample comprised 10 physicians (including three women), (...) aged 33–66 years, residents or specialists in cardiology or cardiothoracic surgery, working in a university hospital with 24-hour emergency service and one general practitioner. Results: Participants described a process by which they were able to develop a capacity for coping with the existential challenges at work. After episodes perceived as shocking or horrible earlier in their career, they at present said that they could deal with death and mostly keep it at a distance. Vulnerability was closely linked to professional responsibility and identity, perceived as a burden to be handled. These demands were balanced by an experience of meaning related to their job, connected to making a difference in their patients’ lives. Belonging to a community of their fellows was a presupposition for coping with the loneliness and powerlessness related to their vulnerable professional position. Conclusions: Physicians’ vulnerability facing life and death has been underestimated. Belonging to caring communities may assist growth and coping on exposure to existential aspects of clinical work and developing a professional identity. (shrink)

One of the earliest and most influential treatises on the subject of this volume is Aristotle's Categories. Aristotle's title is a form of the Greek verb for speaking against or submitting an accusation in a legal proceeding. By the time of Aristotle, it also meant: to signify or to predicate. Surprisingly, the "predicates" Aristotle talks about include not only bits of language, but also such nonlinguistic items as the color white in a body and the knowledge of grammar in a (...) man's soul. (Categories I/ii) Equally surprising are such details as Aristotle's use of the terms 'homonymy' and 'synonymy' in connection with things talked about rather than words used to talk about them. Judging from the evidence in the Organon, the Metaphysics, and elsewhere, Aristotle was both aware of and able to mark the distinction between using and men tioning words; and so we must conclude that in the Categories, he was not greatly concerned with it. For our purposes, however, it is best to treat the term 'predication' as if it were ambiguous and introduce some jargon to disambiguate it. Code, Modrak, and other authors of the essays which follow use the terms 'linguistic predication' and 'metaphysical predication' for this. (shrink)

To localize wheat ESTs on chromosomes, 882 homoeologous group 6-specific ESTs were identified by physically mapping 7965 singletons from 37 cDNA libraries on 146 chromosome, arm, and sub-arm aneuploid and deletion stocks. The 882 ESTs were physically mapped to 25 regions flanked by 23 deletion breakpoints. Of the 5154 restriction fragments detected by 882 ESTs, 2043 were localized to group 6 chromosomes and 806 were mapped on other chromosome groups. The number of loci mapped was greatest on chromosome 6B and (...) least on 6D. The 264 ESTs that detected orthologous loci on all three homoeologs using one restriction enzyme were used to construct a consensus physical map. The physical distribution of ESTs was uneven on chromosomes with a tendency toward higher densities in the distal halves of chromosome arms. About 43% of the wheat group 6 ESTs identified rice homologs upon comparisons of genome sequences. Fifty-eight percent of these ESTs were present on rice chromosome 2 and the remaining were on other rice chromosomes. Even within the group 6 bins, rice chromosomal blocks identified by 1-6 wheat ESTs were homologous to up to 11 rice chromosomes. These rice-block contigs were used to resolve the order of wheat ESTs within each bin. (shrink)

The presence and impact of Hispanics/Latinos in the United States cannot be ignored. Already the largest minority group, by 2050 their numbers will exceed all the other minority groups in the United States combined. The diversity of this population is often understated, but the people differ in terms of their origin, race. language, custom, religion, political affiliation, education and economic status. The heterogeneity of the Hispanic/Latino population raises questions about their identity and their rights: do they really constitute a group? (...) That is, do they have rights as a group, or just as individuals? This volume, addresses these concerns through a varied and interdisciplinary approach. (shrink)

This essay explores the role of God’s omnipresence in Newton’s natural philosophy, with special emphasis placed on how God is related to space. Unlike Descartes’ conception, which denies the spatiality of God, or Gassendi and Charleton’s view, which regards God as completely whole in every part of space, it is argued that Newton accepts spatial extension as a basic aspect of God’s omnipresence. The historical background to Newton’s spatial ontology assumes a large part of our investigation, but with attention also (...) focused on the details of Newton’s unique approach to these traditional Scholastic conceptions. (shrink)

The primary purpose of Institutional Review Boards (IRBs) is to protect the rights and welfare of human research participants. Evaluation and measurement of how IRBs satisfy this purpose and other important goals are open questions that demand empirical research. Research on IRBs, and the Human Research Protection Programs (HRPPs) of which they are often a part, is necessary to inform evidence-based practices, policies, and approaches to quality improvement in human research protections. However, to date, HRPP and IRB engagement in empirical (...) research about their own activities and performance has been limited. To promote engagement of HRPPs and IRBs in self-reflective research on HRPP and IRB quality and effectiveness, barriers to their participation need to be addressed. These include: extensive workloads, limited information technology systems, and few universally accepted or consistently measured metrics for HRPP/irb quality and effectiveness. Additionally, institutional leaders may have concerns about confidentiality. Professional norms around the value of participating in this type of research are lacking. Lastly, obtaining external funding for research on IRBs and HRPPs is challenging. As a group of HRPP professionals and researchers actively involved in a research consortium focused on IRB quality and effectiveness, we identify potential levers for supporting and encouraging HRPP and IRB engagement in research on quality and effectiveness. We maintain that this research should be informed by the core principles of patient- and community-engaged research, in which members and key stakeholders of the community to be studied are included as key informants and members of the research team. This ensures that relevant questions are asked and that data are interpreted to produce meaningful recommendations. As such, we offer several ways to increase the participation of HRPP professionals in research as participants, as data sharers, and as investigators. (shrink)

By building upon Raz's analysis of the spectrum of voluntary obligations, the author produces a typology of agreements, and then assesses the extent to which these different kinds of agreements underpin the common law of contract. While recognizing that the law of contract purports to deal with a broad range of voluntarily undertaken obligations, the typology of agreements suggests that the present law is primarily suited to dealing only with bargains. This suggests that there are situations in which agreements should (...) be legally recognized, but which should not be dealt with by all of the conceptual tools of contract law, for these agreements and voluntary undertakings serve the interests of those undertaking them in significantly different ways than do bargains. (shrink)

This comprehensive reference volume features essays by some of the most distinguished scholars in the field. Provides a comprehensive "who's who" guide to medieval philosophers. Offers a refreshing mix of essays providing historical context followed by 140 alphabetically arranged entries on individual thinkers. Constitutes an extensively cross-referenced and indexed source. Written by a distinguished cast of philosophers. Spans the history of medieval philosophy from the fourth century AD to the fifteenth century.

Lists of species underpin many fields of human endeavour, but there are currently no universally accepted principles for deciding which biological species should be accepted when there are alternative taxonomic treatments (and, by extension, which scientific names should be applied to those species). As improvements in information technology make it easier to communicate, access, and aggregate biodiversity information, there is a need for a framework that helps taxonomists and the users of taxonomy decide which taxa and names should be used (...) by society whilst continuing to encourage taxonomic research that leads to new species discoveries, new knowledge of species relationships, and the refinement of existing species concepts. Here, we present 10 principles that can underpin such a governance framework, namely (i) the species list must be based on science and free from nontaxonomic considerations and interference, (ii) governance of the species list must aim for community support and use, (iii) all decisions about list composition must be transparent, (iv) the governance of validated lists of species is separate from the governance of the names of taxa, (v) governance of lists of accepted species must not constrain academic freedom, (vi) the set of criteria considered sufficient to recognise species boundaries may appropriately vary between different taxonomic groups but should be consistent when possible, (vii) a global list must balance conflicting needs for currency and stability by having archived versions, (viii) contributors need appropriate recognition, (ix) list content should be traceable, and (x) a global listing process needs both to encompass global diversity and to accommodate local knowledge of that diversity. We conclude by outlining issues that must be resolved if such a system of taxonomic list governance and a unified list of accepted scientific names generated are to be universally adopted. (shrink)

David Hume's most brilliant and ambitious work is entitled A Treatise of Human Nature, and it, together with his other writings, has left an indelible mark on philosophical conceptions of human nature. So it is not merely the title of Hume's work that makes discussion of it an appropriate inclusion to this volume, but the fact of its sheer influence. However, its pattern of influence – including, of course, the formulations of ideas consciously antithetical Hume's own – is an immensely (...) complex one, subtle and incredibly difficult to decode. In all probability ‘Hume's’ presence in contemporary thinking of human nature is to likened to the end product of a historiographical game of Chinese whispers, whereby ‘Hume's’ view on x and y is now inflected with interpretations his work – or, more accurately, selected parts of it – that are in turn filtered by thinkers and traditions with different focuses and interest from Hume's own. I am not equipped even to begin to trace this line of influence, a lack compounded by my relative ignorance of the present state of the debate on human nature. Nevetheless various ‘humean’ doctrines still orient debate and I guess these claims include the idea that causation is a matter of instantiating a universal regularity, that normativity can understood causally, that motivation is a matter of belief plus some independently intelligibly ‘attitude’, that a self is best conceived as a collection of independent states that combine to yield a self and so on. (shrink)