© 2015, Springer-Verlag Berlin Heidelberg.Genetic studies have identified single nucleotide polymorphisms associated with the risk of prostate cancer. It remains unclear whether such genetic variants are associated with disease aggressiveness. The NCI-SPORE Genetics Working Group retrospectively collected clinicopathologic information and genotype data for 36 SNPs which at the time had been validated to be associated with PC risk from 25,674 cases with PC. Cases were grouped according to race, Gleason score and aggressiveness. Statistical analyses were used to compare the frequency (...) of the SNPs between different disease cohorts. After adjusting for multiple testing, only PC-risk SNP rs2735839 was significantly and inversely associated with aggressive and high-grade disease in European men. Similar associations with aggressive and high-grade disease were documented in African-American subjects. The G allele of rs2735839 was associated with disease aggressiveness even at low PSA levels in both European and African-American men. Our results provide further support that a PC-risk SNP rs2735839 near the KLK3 gene on chromosome 19q13 may be associated with aggressive and high-grade PC. Future prospectively designed, case-case GWAS are needed to identify additional SNPs associated with PC aggressiveness. (shrink)

Significant associations have been found between specific human leukocyte antigen (HLA) alleles and organ transplant rejection, autoimmune disease development, and the response to infection. Traditional searches for disease associations have conventionally measured risk associated with the presence of individual HLA alleles. However, given the high level of HLA polymorphism, the pattern of amino acid variability, and the fact that most of the HLA variation occurs at functionally important sites, it may be that a combination of variable amino acid sites shared (...) by several alleles (shared epitopes) are better descriptors of the actual causative genetic variants. Here we describe a novel approach to genetic association analysis in which genes/proteins are broken down into smaller sequence features and then variant types defined for each feature, allowing for independent analysis of disease association with each sequence feature variant type. We have used this approach to analyze a cohort of systemic sclerosis patients and show that a sequence feature composed of specific amino acid residues in peptide binding pockets 4 and 7 of HLA-DRB1 explains much of the molecular determinant of risk for systemic sclerosis. (shrink)

This collection of essays on themes in the work of John Locke , George Berkeley , and David Hume , provides a deepened understanding of major issues raised in the Empiricist tradition. In exploring their shared belief in the experiential nature of mental constructs, The Empiricists illuminates the different methodologies of these great Enlightenment philosophers and introduces students to important metaphysical and epistemological issues including the theory of ideas, personal identity, and skepticism. It will be especially useful in courses devoted (...) to the history of modern philosophy. (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)

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.

The application of ontology has thus far [in 1998] been confined almost exclusively to the field of knowledge representation. Ontology has been applied, for example, in the design of medical databases and in the construction of geographical information systems. One area which is naturally suited to ontological analysis is that of the law and of social institutions in general. -/- Legal systems are composed of legal entities, such as laws, contracts, obligations, and rights. Their application yields new categories of entities (...) such as: corporations, trademarks, marriages, and parcels of real estate. The categorization of these entities by different legal systems has not, by-and-large, been conducted in ways which exploit the tools of modern ontology. Consequently, contradictions and inconsistencies often arise in the law when, for instance, one type of entity is forced into two mutually exclusive categories (e.g., when software is considered both patentable and copyrightable). Papers are invited which consider these and related issues from a philosophical point of view. (shrink)

Summary Ian Hunter has made a name for himself as a critic of German university metaphysics, finding its progeny at work in places where many of us would not even think of looking, for example in the late twentieth-century celebration of theory in the humanities. Some of his recent work has focused on a rather different issue: the methodological task of making intellectual history empirical. Here he builds on Quentin Skinner's rationale for the Cambridge School's efforts to make the history (...) of political thought more properly historical. Skinner's argument draws on the work of R. G. Collingwood, at least in its earlier versions, and on neo-Kantian tendencies in mid-twentieth century Oxford philosophy. Thus, in aligning his methodological programme with Skinner's argument, Hunter may risk bringing elements of university metaphysics back in another form. (shrink)

The empirical literature exploring lawyers and their moral decision making is limited despite the “crisis” of unethical and unprofessional behavior in the bar that has been well documented for over a decade. In particular we are unaware of any empirical studies that investigate the moral landscape of the health lawyer’s practice. In an effort to address this gap in the literature, an interdisciplinary team of researchers at Vanderbilt University designed an empirical study to gather preliminary evidence regarding the moral reasoning (...) of health care attorneys. The primary research question was how health lawyers respond when they encounter ethical or moral dilemmas in their practice for which the law fails to offer a bright-line solution. In exploring this question, we sought to understand better what motivations or influences guide action when health lawyers confront ethical quandaries, and whether there are specific differences, e.g., gender, experience, or religiosity, that are associated with specific responses to situations testing ethical or moral boundaries. (shrink)

The analytical philosophy of the last hundred years has been heavily influenced by a doctrine to the effect that the key to the correct understanding of reality is captured syntactically in the ‘Fa’ (or, in more sophisticated versions, in the ‘Rab’) of standard first order predicate logic. Here ‘F’ stands for what is general in reality and ‘a’ for what is individual. Hence “f(a)ntology”. Because predicate logic has exactly two syntactically different kinds of referring expressions—‘F’, ‘G’, ‘R’, etc., and ‘a’, (...) ‘b’, ‘c’, etc.—so reality must consist of exactly two correspondingly different kinds of entity: the general (properties, concepts) and the particular (things, objects). We describe the historical influence of this view, and also show how standard first-order predicate logic can be used for the logical formalization of a more adequate “six category ontology”, which recognizes, at the level of both particulars and universals, not only things or objects but also events and qualities. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:PHARAOH'S.MAGICIANS: THE ETHICS AND EFFICA:CY OF HUMAN FETAiL TISSUE TRANSPLANTS ROBERT BARRY, O.P. Program for the Study of Religion University of Illinois, Champaign-Urbana DARREL KESLER Department of Animal Sciences University of Illinois, Champaign-Urbana. IN RECENT YEARS increasing attention ha;s been given to v:rurious types of scientific riese,arch involving the human fetus. In the 1970s, :a tremendous amount of concern was expres1 sed IJ.'egiaroing the fetus,a;.s a rSU!bject of (...) e~erimenrtation. In this debate, the announced " research impeiiat:i:ve " was pos,ed against other moral imperativ;es.1 Following much soctiet :JaJl drebarte, protootlive meiaisumeis 1 WeIDe il!dopited 1by oompireihensive regiutatiions in 1975 estaiblishiing protections foT a number of research sUibjects. These regulrutions protect the fetus from non-beneficiail experimentation. that iworuild pose more than minima;l risk rto the fetus. Current debates in science and ethics now swirl arlOiund a new topic regarding human '.fetal life: the fetus as a sourrce of tissue for triansplaintation into other persons ais run e~erimental thempy. It is an issue that is rapidly moving torward the same Jevel of" research imperative" as did the earlier debate on the 1 See Paul Ramsey, The Ethics of Fetal Research (New Haven: Yale University Press, 1975): "Today one often hears statements like' Fetal Research must be done,' or 'It would be immoral not to do this research'" (P. xv). The validity of such opinions and utterances entirely depends on a netbenefits ethics, and the validity of that moral universe has been called increasingly into question in recent years. 575 576 ROBERT BARRY, O.P. AND DARREL KESLER ~etus as subject. Recently,,a new level of intensity was added to this deharte rby the imposition of an indefinite moratorium on federal support for research on transplantrution experiments inv;olving human.fetirul tissue and other!humans. 1Thls " :indefinite moratorium " w1as a result of a process that 1 began with research p110posaJs considered rby the National In- 'stituites of Health (NIH) in October 1987. In Marich 1988 a momtorium wa;g plaioed on the r:eseareh, and an 1advisory panel was summoned to consider the ethical issues involved. This panel presented 1a cveoommendation for the procedures. However, the Secretary of the Department of Health and Ruman Se1wfoes (HHS), Dr. Louis Sullivan, decided against the research proposal on etmcal grounds. His decision w:as with the 'concU'l'Tenoe of the Assistant Secretary :£m.· Health of HHS, Dr. James Mason, who has Tespons~bility for the NIH. Secretary SulliV1an's decision was oommumcarted to the Acting Director of the NIH, Dr. William Raub, in Nov,ember 1989. A :firestorm of criticism erupted from,rudv;ocates of this research, including the Council of Judicial and Ethical Affairs of tihe American Medical Association, which 5.n June 1989 called for an end to the:ban.2 In this article, we wish to question both the science and the ethics of the rproposed fotal tissue transplantation therapy. We!Will 1support the £edeml funding moratorium and surggest new pmtections for the fetuses (whether po,ssibly living or de2 " Medical Applications of Fetal Tissue Transplantation", JAMA, Vol. 263, No. 4, January 26, 1990, 'PP· 565-570. There has been a.great deal of public debate, not only in the U.S. but also in Europe over whether human embryo research should be supported with public funds. Many Catholic countries in Europe have prohibited such research, while a number of other nations have allowed it. Dickson, D., "Europe Split on Embyro Research", Science, Vol. 242, November 21, 1988, pp. 1117-1118. The most interesting controversy is in West Germany where there is a strong movement to prohibit it because many there believe such an experimentation requires judgments that there are certain forms of human life that do not deserve to survive. Ibid., p. 1117. Many Germans regard these sorts of judgments as too close to those made by Nazis, and there is strong sentiment to prohibit such research altogether. Ibid. HUMAN FETAL TISSUE TRANSPLANTS 577 oea:sed) of elective a.bortfons. We will also describe new reseaooh directions in t~apy.for the diseases in which it is claimed that fetal... (shrink)

Frankena, W. K. Morality and moral philosophy.--Soltis, J. F. Men, machines and morality.--Chazan, B. I. The moral situation.--Phenix, P. H. Ethics and the will of God.--Moore, G. E. The indefinability of good.--Morgenbesser, S. Approaches to ethical objectivity.--Sartre, J. P. Existentialism and ethics.--Hare, R. M. Decisions of principle.--Singer, M. G. Moral rules and principles.--Hare, R. M. Adolescents into adults.--Wilson, J. Assessing the morally educated person.--Kohlberg, L. The child as a moral philosopher.--Frankena, W. K. Toward a philosophy of moral education.--Archambault, R. D. (...) Criteria for success in moral instruction.--Raths, L., Harmin, M., and Simon, S. Teaching for value clarity.--Bibliography (p. 188-192). (shrink)

Deontological evidentialism is the claim that we ought to form and maintain our beliefs in accordance with our evidence. In this paper, I criticize two arguments in its defense. I begin by discussing Berit Broogard’s use of the distinction between narrow-scope and wide-scope requirements against W.K. Clifford’s moral defense of. I then use this very distinction against a defense of inspired by Stephen Grimm’s more recent claims about the moral source of epistemic normativity. I use this distinction once again to (...) argue that Hilary Kornblith’s criticism of Richard Feldman’s defense of is incomplete. Finally, I argue that Feldman’s defense is insensitive to the relation between normative requirements and privileged values: values that have normative authority over us. (shrink)

Deontological internalism is the family of views where justification is a positive deontological appraisal of someone's epistemic agency: S is justified, that is, when S is blameless, praiseworthy, or responsible in believing that p. Brian Weatherson discusses very briefly how a plausible principle of ampliative transmission reveals a worry for versions of deontological internalism formulated in terms of epistemic blame. Weatherson denies, however, that similar principles reveal similar worries for other versions. I disagree. In this article, I argue that plausible (...) principles of ampliative transmission reveal a worry for deontological internalism in general. (shrink)

This paper defends a novel account of how to determine the intrinsic value of possible worlds. Section 1 argues that a highly intuitive and widely accepted account leads to undesirable consequences. Section 2 takes the first of two steps towards a novel account by clarifying and defending a view about value-contribution that is based on some of W. D. Ross’ claims about the value of pleasure. Section 3 takes the second step by clarifying and defending a view about value-suppression that (...) is based on Ross’ claims about the interplay between prima-facie duties. Section 4 states and defends the account that I call Rossian Totalism. According to this account, the atoms of intrinsic value within a world only sometimes contribute their intrinsic value to the value of that world. (shrink)

The claim that ordinary ethical discourse is typically true and that ethical facts are typically knowable seems in tension with the claim that ordinary ethical discourse is about features of reality friendly to a scientific worldview. Cornell Realism attempts to dispel this tension by claiming that ordinary ethical discourse is, in fact, discourse about the same kinds of things that scientific discourse is about: natural properties. We offer two novel arguments in reply. First, we identify a key assumption that we (...) find unlikely to be true. Second, we identify two features of typical natural properties that ethical properties lack. We conclude that Cornell Realism falls short of dispelling the tension between ethical conservativism and ethical naturalism. (shrink)

First published in 1998, this volume argues that two conditions need to be met for any agreement between people with conflicting desires to count as an unforced one, namely, that the parties argue as if they had equal power and that their antipathy to being coerced exceeds their desire to coerce others. These conditions entail objective moral principles and a theory of justice, modifying and developing Rawls' contractarian theory, but without the veil of ignorance. They support Rawls on basic civil (...) liberties and constitutional liberal democratic government, including religious tolerance, anti-paternalism, anti-racism and anti-sexism, but dispute his Difference Principle, his circumstances of justice, Laws of Peoples, reflective equilibrium, and freedom of conscience as a basic liberty. The book also gives a contractarian account of epistemology, metaethics, education, the rationality of being moral, the rights of animals and other non-persons, and the rights of indigenous peoples. Writers such as Brian Barry, R.S. Peters, Isaiah Berlin, Vinit Haksar, Jurgen Habermas, R.M. Hare, Philip Pettit, Derek Parfit, Michael Smith, Peter Geach, Philippa Foot, Bronwyn Davies, Quentin Skinner and Will Kymlicka are also discussed. (shrink)

The 2010 Nagoya Protocol is an international framework for access and benefit sharing (ABS) of the use of genetic and biological resources, with particular focus on indigenous communities. This is especially important in Africa, where local communities have a close reliance on environmental resources and ecosystems. However, national legislation and policies commonly lag behind international agreements, and this poses challenges for legal compliance as well as practical applications. This study reviews the academic literature on the Nagoya Protocol and ABS applications, (...) and then considers the implications of this analysis for research in Africa. Results show that there is uneven engagement with the principles of the Nagoya Protocol across different academic disciplines; local communities are sometimes sidelined in these studies; and only 8% of researchers in the literature analysed are located in Africa. Future developments should focus on ensuring national compliance with the Nagoya Protocol, and that researchers and industry work in partnership with local African communities on ABS issues. (shrink)

An impressive book whose purpose is to "relate the outstanding events of contemporary life and thought to the accumulated wisdom of the past." Forming part of the series The Great Books of the Western World, its contributors are among the most qualified in their fields: Alfred Kazin, George Gamow, Irving Kristol, Karl Ubell, and James Collins, not to mention the editors themselves. Five parts make up the book: in Part I, The Great Debate of the Year: "Does America's best hope (...) for the future lie in political conservatism?", Barry Goldwater speaks for the affirmative and Jacob Javits for the negative; Part II, The Editors' Review of the Year, analyzes three problems as yet unsolved: the divided world, automation, and television; Part III, the largest portion of the work, reviews the contemporary scene in literature, physical science and technology, social sciences and law, biology and medicine, and philosophy and religion ; Part IV offers four important additions to the Great Books Library: M. Luther's The Freedom of a Christian, R. H. Tawney's The Acquisitive Society, Max Planck's The Universe in the Light of Modern Physics, and James Joyce's The Dead; finally, Part V gives a bibliography of significant books published in the last ten years.--V. G. P., S. J. (shrink)