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)

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)

This report describes the rationale, approaches, organization, and resource development leading to a large-scale deletion bin map of the hexaploid wheat genome. Accompanying reports in this issue detail results from chromosome bin-mapping of expressed sequence tags representing genes onto the seven homoeologous chromosome groups and a global analysis of the entire mapped wheat EST data set. Among the resources developed were the first extensive public wheat EST collection. Described are protocols for sequencing, sequence processing, EST nomenclature, and the assembly of (...) ESTs into contigs. These contigs plus singletons were used for selection of distinct sequence motif unigenes. Selected ESTs were rearrayed, validated by 5′ and 3′ sequencing, and amplified for probing a series of wheat aneuploid and deletion stocks. Images and data for all Southern hybridizations were deposited in databases and were used by the coordinators for each of the seven homoeologous chromosome groups to validate the mapping results. Results from this project have established the foundation for future developments in wheat genomics. (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)

There are methodological problems with the new techniques reviewed by Posner & Raichle. Some brain mechanisms are not detected by the temporal and spatial resolution. Questions are also raised by the stimulation paradigms.

Analogies must be symmetric. If a is like b, then b is like a. So if a has property R, and if R is within the scope of the analogy, then b (probably) has R. However, analogical arguments generally single out, or depend upon, only one of a or b to serve as the basis for the inference. In this respect, analogical arguments are directed by an asymmetry. I defend the importance of this neglected – even when explicitly mentioned – (...) feature in understanding analogical arguments. (shrink)

Prologue: Stormclouds : London, April 1900 -- Quantum of action: The most strenuous work of my life : Berlin, December 1900 ; Annus Mirabilis : Bern, March 1905 ; A little bit of reality : Manchester, April 1913 ; la Comédie Française : Paris, September 1923 ; A strangely beautiful interior : Helgoland, June 1925 ; The self-rotating electron : Leiden, November 1925 ; A late erotic outburst : Swiss Alps, Christmas 1925 -- Quantum interpretation: Ghost field : Oxford, August (...) 1926 ; All this damned quantum jumping : Copenhagen, October 1926 ; The uncertainty principle : Copenhagen, February 1927 ; The 'Kopenhagener geist' : Copenhagen, June 1927 ; There is no quantum world : Lake Como, September 1927 -- Quantum debate: The debate commences : Brussels, October 1927 ; An absolute wonder : Cambridge, Christmas 1927 ; The photon box : Brussels, October 1930 ; A bolt from the blue : Princeton, May 1935 ; The paradox of Schrödinger's cat : Oxford, August 1935 -- Interlude: The first war of physics : Christmas 1938-August 1945 -- Quantum fields: Shelter Island : Long Island, June 1947 ; Pictorial semi-vision thing : New York, January 1949 ; A beautiful idea : Princeton, February 1954 ; Some strangeness in the proportion : Rochester, August 1960 ; Three quarks for Muster Mark! : New York, March 1963 ; The 'God particle' : Cambridge, Massachusetts, Autumn 1967 -- Quantum particles: Deep inelastic scattering : Stanford, August 1968 ; Of charm and weak neutral currents : Harvard, February 1970 ; The magic of colour : Princeton/Harvard, April 1973 ; The November revolution : Long Island/Stanford, November 1974 ; Intermediate vector bosons : Geneva, January/June 1983 ; The standard model : Geneva, September 2003 -- Quantum reality: Hidden variable : Princeton, Spring 1951 ; Bertlmann's socks : Boston, September 1964 ; The Aspect experiments : Paris, September 1982 ; The quantum eraser : Baltimore, January 1999 ; Lab cats : Stony Brook/Delft, July 2000 ; The persistent illusion : Vienna, December 2006 -- Quantum cosmology: The wavefunction of the universe : Princeton, July 1966 ; Hawking radiation : Oxford, February 1974 ; The first superstring revolution : Aspen, August 1984 ; Quanta of space and time : Santa Barbara, February 1986 ; Crisis? What crisis? : Durham, Summer 1994 -- A quantum of solace? : Geneva, March 2010. (shrink)

The discussion of the relation of levels of reality to categories is important because categories have often been interpreted as constituting levels of reality. This article explores whether this view is correct, and argues it is not. Categories as such should not be understood to constitute levels of reality, although particular categories may. The article begins with a discussion of levels of reality and then turns to specific questions about categories and how they are related to these levels.

THE AUDIENCE IS THE REAL or imaginary group of persons who are in fact acquainted, could be acquainted, or are meant to be acquainted with a given text. Etymologically, the term "audience" refers to a group of listeners. This meaning of the term goes back to a time when the primary form of acquaintance with the work of an author was through the spoken word. From the invention of the printing press, however, until the time when the use of the (...) radio became widespread, written texts were the primary way of learning about an author's work. Although contemporary media have changed this to a certain extent, in science and the humanities it is still true that the audience for an author's work consists largely of readers. For my present purposes, the distinction between readers and listeners is immaterial and, hence, I often refer to an audience as a group of readers, although what I say about it will apply, mutatis mutandis, to listeners as well. (shrink)

Although Professor of Philosophy at Calvin College, Alvin Plantinga has developed a theodicy that is fundamentally Arminian rather than Calvinistic. Anthony Flew, although the son of an Arminian Christian minister, regards the Arminian view of ‘free will’ to be both unacceptable on its own terms and incompatible with classical Christian theism. In this paper I hope to disentangle some of the involved controversy regarding theodicy which has developed between Plantinga and Flew, and between Flew and myself. The major portion of (...) this paper is devoted to showing that Plantinga's theodicy contains some serious flaws and undesirable implications. (shrink)

In a recent number of this journal there appeared an article by Niall Shanks and John King-Farlow on the theory of radical interpretation as developed by Donald Davidson. In that paper Davidson was presented as an opponent of “metaphysical openness in general [and] … idealism in particular” and as a philosopher who has “sought to silence all philosophically challenging talk both about the ordinary speaker’s systematic errors and about the claims of revisionary metaphysicians such as phenomenalists or absolute idealists.” I (...) suspect that Davidson would be somewhat surprised by this description of himself. He might also wonder just what it means to be an “opponent of metaphysical openness in general.” Like any other philosopher, Davidson has his own views on matters philosophical; and, like other philosophers, he criticizes what he sees as false or mistaken in the views of others. One cannot help but suspect that what Davidson’s opposition to “metaphysical openness” really comes down to is his criticism of views associated with idealism. (shrink)