The power of the application of bioinformatics across multiple publicly available transcriptomic data sets was explored. Using 19 human and mouse circadian transcriptomic data sets, we found that NR1D1 and NR1D2 which encode heme‐responsive nuclear receptors are the most rhythmic transcripts across sleep conditions and tissues suggesting that they are at the core of circadian rhythm generation. Analyzes of human transcriptomic data show that a core set of transcripts related to processes including immune function, glucocorticoid signalling, and lipid metabolism is (...) rhythmically expressed independently of the sleep‐wake cycle. We also identify key transcripts associated with transcription and translation that are disrupted by sleep manipulations, and through network analysis identify putative mechanisms underlying the adverse health outcomes associated with sleep disruption, such as diabetes and cancer. Comparative bioinformatics applied to existing and future data sets will be a powerful tool for the identification of core circadian‐ and sleep‐dependent molecules. (shrink)

Although the neoconservative movement has come to dominate American conservatism, this movement has its origins in the old Marxist Left. Communists in their younger days, as the founders of neoconservatism, inverted Marxist doctrine by arguing that moral values and not economic forces were the primary movers of history. Yet the neoconservative critique of biotechnology still borrows heavily from Karl Marx and owes more to the German philosopher Martin Heidegger than to the Scottish philosopher and political economist Adam Smith. Loath (...) to identify these sources - or perhaps unaware of them - neoconservatives do not acknowledge these intellectual underpinnings or their implications. Thus, in the final analysis, their critique is incoherent and even internally inconsistent. By not acknowledging and embracing their intellectual roots, neoconservatives are left with a deeply ambivalent and often confused view of biotechnology and the society that gives rise to it. (shrink)

Integrating concepts of maintenance and of origins is essential to explaining biological diversity. The unified theory of evolution attempts to find a common theme linking production rules inherent in biological systems, explaining the origin of biological order as a manifestation of the flow of energy and the flow of information on various spatial and temporal scales, with the recognition that natural selection is an evolutionarily relevant process. Biological systems persist in space and time by transfor ming energy from one state (...) to another in a manner that generates structures which allows the system to continue to persist. Two classes of energetic transformations allow this; heat-generating transformations, resulting in a net loss of energy from the system, and conservative transformations, changing unusable energy into states that can be stored and used subsequently. All conservative transformations in biological systems are coupled with heat-generating transformations; hence, inherent biological production, or genealogical proesses, is positively entropic. There is a self-organizing phenomenology common to genealogical phenomena, which imparts an arrow of time to biological systems. Natural selection, which by itself is time-reversible, contributes to the organization of the self-organized genealogical trajectories. The interplay of genealogical (diversity-promoting) and selective (diversity-limiting) processes produces biological order to which the primary contribution is genealogical history. Dynamic changes occuring on times scales shorter than speciation rates are microevolutionary; those occuring on time scales longer than speciation rates are macroevolutionary. Macroevolutionary processes are neither redicible to, nor autonomous from, microevolutionary processes. (shrink)

Monoclonal antibodies are essential biomedical research and clinical reagents that are produced by companies and research laboratories. The NIAID ImmPort (Immunology Database and Analysis Portal) resource provides a long-term, sustainable data warehouse for immunological data generated by NIAID, DAIT and DMID funded investigators for data archiving and re-use. A variety of immunological data is generated using techniques that rely upon monoclonal antibody reagents, including flow cytometry, immunofluorescence, and ELISA. In order to facilitate querying, integration, and reuse of data, standardized terminology (...) for describing monoclonal antibody reagents and their targets needs to be used for annotating data submitted to ImmPort. (shrink)

What determines whether an action is right or wrong? Morality, Rules, and Consequences: A Critical Reader explores for students and researchers the relationship between consequentialist theory and moral rules. Most of the chapters focus on rule consequentialism or on the distinction between act and rule versions of consequentialism. Contributors, among them the leading philosophers in the discipline, suggest ways of assessing whether rule consequentialism could be a satisfactory moral theory. These essays, all of which are previously unpublished, provide students in (...) moral philosophy with essential material and ask key questions on just what the criteria for an adequate moral theory might be. (shrink)

1 Evidence-based policy requires researchers to provide the answers to ecological questions that are of interest to policy makers. To find out what those questions are in the UK, representatives from 28 organizations involved in policy, together with scientists from 10 academic institutions, were asked to generate a list of questions from their organizations. 2 During a 2-day workshop the initial list of 1003 questions generated from consulting at least 654 policy makers and academics was used as a basis for (...) generating a short list of 100 questions of significant policy relevance. Short-listing was decided on the basis of the preferences of the representatives from the policy-led organizations. 3 The areas covered included most major issues of environmental concern in the UK, including agriculture, marine fisheries, climate change, ecosystem function and land management. 4 The most striking outcome was the preference for general questions rather than narrow ones. The reason is that policy is driven by broad issues rather than specific ones. In contrast, scientists are frequently best equipped to answer specific questions. This means that it may be necessary to extract the underpinning specific question before researchers can proceed. 5 Synthesis and applications. Greater communication between policy makers and scientists is required in order to ensure that applied ecologists are dealing with issues in a way that can feed into policy. It is particularly important that applied ecologists emphasize the generic value of their work wherever possible. (shrink)

We report the identification of a recurrent, 520-kb 16p12.1 microdeletion associated with childhood developmental delay. The microdeletion was detected in 20 of 11,873 cases compared with 2 of 8,540 controls and replicated in a second series of 22 of 9,254 cases compared with 6 of 6,299 controls. Most deletions were inherited, with carrier parents likely to manifest neuropsychiatric phenotypes compared to non-carrier parents. Probands were more likely to carry an additional large copy-number variant when compared to matched controls. The clinical (...) features of individuals with two mutations were distinct from and/or more severe than those of individuals carrying only the co-occurring mutation. Our data support a two-hit model in which the 16p12.1 microdeletion both predisposes to neuropsychiatric phenotypes as a single event and exacerbates neurodevelopmental phenotypes in association with other large deletions or duplications. Analysis of other microdeletions with variable expressivity indicates that this two-hit model might be more generally applicable to neuropsychiatric disease. © 2010 Nature America, Inc. All rights reserved. (shrink)

Pancreatitis is a complex, progressively destructive inflammatory disorder. Alcohol was long thought to be the primary causative agent, but genetic contributions have been of interest since the discovery that rare PRSS1, CFTR and SPINK1 variants were associated with pancreatitis risk. We now report two associations at genome-wide significance identified and replicated at PRSS1-PRSS2 and X-linked CLDN2 through a two-stage genome-wide study. The PRSS1 variant likely affects disease susceptibility by altering expression of the primary trypsinogen gene. The CLDN2 risk allele is (...) associated with atypical localization of claudin-2 in pancreatic acinar cells. The homozygous CLDN2 genotype confers the greatest risk, and its alleles interact with alcohol consumption to amplify risk. These results could partially explain the high frequency of alcohol-related pancreatitis in men. © 2012 Nature America, Inc. All rights reserved. (shrink)

Le présent article est une tentative nouvelle d’articuler le rôle d’une théorie des vérifacteurs. Nous soutenons que la théorie de la vérifaction constitue une pierre angulaire dans une bonne méthodologie en métaphysique, mais que l’amalgame entre la théorie de la vérifaction et la théorie de la vérité a été responsable de certains excès associés aux approches vérifactionnistes dans la littérature récente. Nous montrons que la théorie de la vérifaction conserve son attrait comme instrument d’investigation métaphysique, et ce, malgré notre accord (...) avec les doctrines déflationnistes telles que celles défendues par Ayer, Quine, Field et Horwich (ou, du moins, malgré notre neutralité à leur égard). Nous soutenons en outre que les intuitions sous-jacentes à la théorie de la vérifaction s’éclairent quand nous les dissocions d’une théorie de la vérité et, par-dessus tout, de la tentative de fournir une définition de la vérité. (shrink)

Western society today is less unified by a set of core values than ever before. Undoubtedly, the concept of moral consensus is a difficult one in a liberal, democratic and pluralistic society. But it is imperative to avoid a rigid majoritarianism where sensitive personal values are at stake, as in bioethics. Bioethics has become an influential part of public and professional discussions of health care. It has helped frame issues of moral values and medicine as part of a more general (...) effort to find consensus about some of the most perplexing questions of our time. But why is it thought that a moral consensus is important or that it deserves respect? How does moral consensus acquire legitimacy in a society that includes diverse value systems? How is moral consensus possible and how do small groups help create or distort consensus processes? Written by a medical school professor trained in philosophy, this timely work tackles these questions from philosophical, historical, and social scientific standpoints. It begins by describing the traditional ambivalence about consensus in Western culture as well as the uncertain relationship in modernity between consensus and expertise. After outlining the current bioethical consensus, the book gives philosophical and political analyses of the idea of consensus, then assesses the role of consensus in national ethics commissions and in the ethics committee movement. Moreno constructs an original, naturalistic philosophy of moral consensus, referred to as "bioethical naturalism", and then applies sociology and social psychology to actual consensus processes. The book concludes with an account of bioethics as a consensus-oriented social reform movement. This insightful volume will be essential reading for bioethicists, philosophers, physicians, members of ethics committees, and all those concerned with ethical and social issues in health care. (shrink)

Color provides an instance of a general puzzle about how to reconcile the picture of the world given to us by our ordinary experience with the picture of the world given to us by our best theoretical accounts. The Red and the Real offers a new approach to such longstanding philosophical puzzles about what colors are and how they fit into nature. It is responsive to a broad range of constraints --- both the ordinary constraints of color experience and the (...) more theoretical constraints of color science, psychology, semantics, and ontology. (shrink)

Three claims are widely held and individually plausible, but jointly inconsistent: (1) Negative actions (intentional omissions, refrainments, etc.) are genuine actions; (2) All actions are events; (3) Some, and perhaps all, negative actions aren't events, but absences thereof (when I omit to raise my arm, no omission-event occurs; what happens is just that no arm-raising occurs). Drawing on resources from metaphysics and the philosophy of language, I argue that (3) is false. Negative actions are events, just as ordinary actions are. (...) Moreover, each token negative action is identical to a token positive event, so we can adopt this realist view of negative actions without adding metaphysically negative entities (absences, negative states of affairs) to our ontology. (shrink)

The generality problem is perhaps the most notorious problem for process reliabilism. Several recent responses to the generality problem have claimed that the problem has been unfairly leveled against reliabilists. In particular, these responses have claimed that the generality problem is either (i) just as much of a problem for evidentialists, or (ii) if it is not, then a parallel solution is available to reliabilists. Along these lines, Juan Comesaña has recently proposed solution to the generality problem—well-founded reliabilism. According to (...) Comesaña, the solution to the generality problem lies in solving the basing problem, such that any solution to the basing problem will give a solution to the generality problem. Comesaña utilizes Conee and Feldman’s evidentialist account of basing (Conee and Feldman’s well-foundedness principle) in forming his version of reliabilism. In this paper I show that Comesaña’s proposed solution to the generality problem is inadequate. Well-founded reliabilism both fails to solve the generality problem and subjects reliabilism to new damning verdicts. In addition, I show that evidentialism does not face any parallel problems, so the generality problem remains a reason to prefer evidentialism to reliabilism. (shrink)

I claim that a whole is identical to its parts. Many find this claim incredible: it seems that a whole and its parts must be distinct, for the whole is one thing while its parts are many things. Byeong-uk Yi has developed a version of this argument which exploits the resources of plural logic. Yi provides logical analyses of the predicates ‘one’ and ‘many’ which seem to show that nothing can satisfy them both. But there are two senses of the (...) word ‘one’. One of these senses is not captured by Yi’s analysis, and in this sense of the word, it is logically possible for many things to be one. Moreover, we should only believe that a whole is one thing in this sense, not that it is one thing in the sense Yi has analysed. Thus, we can identify wholes with their parts without contradiction. (shrink)

Timely and provocative essays on bioethical questions brought to the forefront by the bioterrorist threat.

It is often assumed that, while ordinary actions are events, ‘negative actions’ are absences of events. I claim that a negative action is an ordinary, ‘positive’ event that plays a certain role. I argue that my approach can answer standard objections to the identity of negative actions and positive events.

I explore two accounts of properties within a dispositional essentialist (or causal powers) framework, the pure powers view and the powerful qualities view. I first attempt to clarify precisely what the pure powers view is, and then raise objections to it. I then present the powerful qualities view and, in order to avoid a common misconception, offer a restatement of it that I shall call the truthmaker view. I end by briefly defending the truthmaker view against objections.

Possible worlds, concrete or abstract as you like, are irrelevant to the truthmakers for modality—or so I shall argue in this paper. First, I present the neo-Humean picture of modality, and explain why those who accept it deny a common sense view of modality. Second, I present what I take to be the most pressing objection to the neo-Humean account, one that, I argue, applies equally well to any theory that grounds modality in possible worlds. Third, I present an alternative, (...) properties-based theory of modality and explore several specific ways to flesh the general proposal out, including my favored version, the powers theory. And, fourth, I offer a powers semantics for counterfactuals that each version of the properties-based theory of modality can accept, mutatis mutandis. Together with a definition of possibility and necessity in terms of counterfactuals, the powers semantics of counterfactuals generates a semantics for modality that appeals to causal powers and not possible worlds. (shrink)

Recently Trent Dougherty has claimed that there is a tension between skeptical theism and common sense epistemology—that the more plausible one of these views is, the less plausible the other is. In this paper I explain Dougherty’s argument and develop an account of defeaters which removes the alleged tension between skeptical theism and common sense epistemology.

Metaphysicians of various stripes claim that a single object can have more than one exact location in space or time – e.g. endurantists claim that an object persists by being ‘all there’ at different moments in time. Antony Eagle has developed a formal theory of location which is prima facie consistent with multi-location, but Damiano Costa and Claudio Calosi argue that the theory is unattractive to multi-location theorists on other grounds. I examine their charge that Eagle’s theory won’t allow an (...) endurantist to account for certain cases of mereological change. I argue that the charge sticks, but not for the reasons Costa and Calosi think. Along the way, I explore an issue which is underexplored in their paper, namely, how an endurantist might modify Eagle’s theory to incorporate a parthood relation which obtains, not absolutely, but only relative to times. (shrink)

It is typically assumed that actions are events, but there is a growing consensus that negative actions, like omissions and refrainments, are not events, but absences thereof. If so, then we must either deny the obvious, that we can exercise our agency by omitting and refrainment, or give up on event-based theories of agency. I trace the consensus to the assumption that negative action sentences are negative-existentials, and argue that this is false. The best analysis of negative action sentences treats (...) them as quantifying over omissions and refrainments, conceived of as events. (shrink)

In her foreword to Science Next, Elizabeth Edwards wrote of science as a tool for social progress: "Innovation is not simply the abstract victory of knowledge [or] the research that gave me years to live; the next science can advance human flourishing and serve the common good. That's the kind of world I want to leave for my children, and for yours." With these words, she joined a tradition that goes back to America's founders, who saw America itself as a (...) "great experiment." Yet while no one can deny that science undergirds the American Dream, it has long been fertile terrain for the "culture wars." Along with arguing the pros and cons of abortion and healthcare, policymakers must now grapple with advancements that raise questions about what it means to be human: we've decoded the genome, but should we modify it to enhance certain "desirable" traits? If we can, should we prolong life at any cost? Will we soon be counting robots, cyborgs, and chimeras among our friends and family?The first book to unpack our love/hate relationship with science from our country's origins to today, The Body Politic is essential reading for science buffs and concerned citizens alike.Jonathan D. Moreno is editor of the Center for American Progress' online magazine Science Progress and professor of bioethics at the University of Pennsylvania. Author and editor of many seminal books and articles on science and science policy, he divides his time between Philadelphia, PA, and Washington, DC. (shrink)

Leading scholars debate politically progressive perspectives on bioethics and the implications for society, politics, and science in the twenty-first century.

In lieu of an abstract, here is a brief excerpt of the content:IRBs Under the MicroscopeJonathan D. Moreno (bio)The spring and summer of 1998 were seasons in the sun for institutional review board (IRB) aficionados. Rarely have the arcana of the local human subjects review panels been treated to so much attention in both the executive and the legislative branches of government, not only at the federal but also at the state level. And it looks as if the attention will (...) continue for some time. The spate of interest is due to a series of coincidences: a powerful House of Representatives subcommittee held hearings after its chairman learned about the IRB system during a previous session on research in underdeveloped communities; the Department of Health and Human Services’s Inspector General (DHHS-IG) released a report on IRBs; the National Institutes of Health (NIH) Office of Extramural Research completed a report on clinical trial monitoring; the National Bioethics Advisory Commission (NBAC) readied a report on research involving persons with mental disorders; the states of Maryland and New York completed studies of research with subjects who lack decision-making capacity; and advocacy groups protested a psychiatric research project involving inner city children.Underlying these proximate causes for the IRB blitz is a growing realization that the already considerable clinical trial enterprise will expand significantly over the next few years. Congress is talking about giving the politically popular NIH half again the budget it currently receives, which in turn will stimulate more commercially supported research. The director of the National Cancer Institute is considering a five-fold increase in the number of subjects enrolled in oncology studies over the next several years. Phase I cancer studies are among the most ethically sensitive, so IRBs will have more work cut out for them if this goal is reached. Adding to the rush of interest in IRBs are the government’s recent apology to the survivors of the syphilis study in Tuskegee, continuing congressional dissatisfaction with the way the Pentagon handled its vaccine distribution during the Gulf War, and the controversy about AZT trials in developing countries.On the HillCongressman Christopher Shays, the moderate Connecticut Republican who has developed an interest in human research issues, convened hearings on human [End Page 329] subjects research and the IRB system on 11 June 1998. Shays chairs the House Government Reform/Human Resources Subcommittee. The committee’s ranking minority member is Edolphus Towns of Brooklyn, NY, who shares Shays’s interest in this area.The immediate rationale for the hearings was the release that day of the DHHS-IG report, Institutional Review Boards: A Time for Reform. The subtitle was changed from A System in Jeopardy apparently after some people in DHHS expressed reservations about its seemingly alarmist tone, but the IG staffers who testified before Shays’s subcommittee insisted that they stood behind the message that the IRB system is in trouble if considerable reforms are not undertaken. Among the factors in the research environment cited as support for the bleak forecast: managed care, commercialization, multi-site trials, high IRB workloads, minimal IRB oversight of approved studies, conflicts of interest, insufficient training of IRB members and investigators, and lack of IRB self-studies (DHHS-IG 1998).As is normally the case for congressional oversight hearings, the first panel of witnesses consisted of executive branch officials, including Eric Meslin, Executive Director of the National Bioethics Advisory Commission, and Gary Ellis, Director of the Office for Protection from Research Risks (OPRR). Shays pressed Ellis on the extent to which OPRR conducts on-site investigations of complaints about abuse of human subjects. Admitting that on-site investigations are rare, Ellis suggested that the agency is inadequately staffed to follow up on complaints as quickly as it might wish. The members of Congress who were present at the hearings generally expressed concern about the DHHS-IG’s findings.The second panel that day, which Shays was unable to attend, set a different tone. Four of the panelists—Paul Appelbaum of the University of Massachusetts at Worcester, Robert Levine of Yale University, Angela Bowen of the Western IRB (a private clinical trials review firm), and I—were invited as authorities on the current condition of the IRB system. Bert Spilker... (shrink)

I defend the thesis that Composition Entails Identity (CEI): that is, a whole is identical to all of its parts, taken together. CEI seems to be inconsistent, since it seems to require that the parts of a whole possess incompatible number properties (for instance, being one thing and being many things). I show that these number properties are, in fact, compatible.

Accustomed as many of us have become in the era of clinical bioethics to the idea of a “hospital philosopher”, on reflection the historical novelty of the role is astonishing, as are its ambiguities. As a result of considering my own experience I found myself writing this miniature intellectual autobiography. In the course of this essay I raise two specific questions: what can the Western philosophical tradition contribute to the clinical setting; and (a question that is rarely asked), what are (...) the implications of this experience for that tradition? (shrink)

We use concepts of causal powers and their relatives-dispositions, capacities, and abilities-to describe the world around us, both in everyday life and in scientific practice. This volume presents new work on the nature of causal powers, and their connections with other phenomena within metaphysics, philosophy of science, and philosophy of mind.

Consensus is commonly identified as the goal of ethics committee deliberation, but it is not clear what is morally authoritative about consensus. Various problems with the concept of an ethics committee in a health care institution are identified. The problem of consensus is placed in the context of the debate about realism in moral epistemology, and this is shown to be of interest for ethics committees. But further difficulties, such as the fact that consensus at one level of discourse need (...) not imply consensus at another, oblige us to look more closely at the deliberative process itself. That yields two complementary methods of deliberation that have proven their worth. Finally, placing ethics committees in the context of Dewey's philosophy of social intelligence suggests that consensus should be regarded primarily as a condition rather than as the goal of inquiry. Keywords: ethics committee, consensus, moral authority CiteULike Connotea Del.icio.us What's this? (shrink)

Freedom and moral responsibility have one foot in the practical realm of human affairs and the other in the esoteric realm of fundamental metaphysics—or so we believe. This has been denied, especially in the metaphysics-bashing era occupying the first two-thirds or so of the twentieth century, traces of which linger in the present day. But the reasons for this denial seem to us quite implausible. Certainly, the argument for the general bankruptcy of metaphysics has been soundly discredited. Arguments from Strawson (...) and others that our moral practices are too deeply embedded in human life to rest on anything as tenuous as a metaphysical doctrine far from the thoughts of ordinary people would seem to prove too much: we can easily imagine fantastic scenarios far from the thoughts of ordinary people—involving, say, alien manipulation or massive deception—that, if true, would clearly undermine claims to freedom and responsibility. For still other philosophers, the separation of the moral life from (some) metaphysical issues is prescriptive, not descriptive: it is a recommendation that we revise ordinary moral thought by severing its allegedly problematic links to metaphysics. (Some philosophers appear to hover undecided between such a prescriptive project and a Strawsonian descriptive claim.) We suspect that the prospects of retaining the binding force of ordinary moral thought, were such a reconceived moral practice widely embraced, are bleak. A transition to something closer to moral nihilism seems at least as likely. In any case, our interest here is in descriptive metaphysics, not revisionary. -/- To say as we do that freedom and moral responsibility have a partly metaphysical character is not to suggest that they can be had only if some highly specific version of a particular metaphysical framework is correct. Instead, we suggest in what follows, it is a broadly neo-Humean metaphysics that is not hospitable to freedom (for reasons distinctive to the metaphysics), while a broadly neo-Aristotelian metaphysics is. But we also think (and it is the main aim of our paper to show) that different versions of the neo- Aristotelian metaphysics lead to rather different metaphysical accounts of free and responsible action. Specifically, we will argue that (1) the most satisfactory account of human freedom within the broadly neo-Aristotelian metaphysics is agent-causal, but that (2) two different versions of the general metaphysics will lead to important differences in the agent-causal account of freedom. Adjust the details of your general metaphysics, and the details of your account of freedom are transformed in significant ways. Action theory cannot properly be pursued in isolation from general metaphysics. (shrink)

D. M. Armstrong famously claims that deterministic laws of nature are contingent relations between universals and that his account can also be straightforwardly extended to irreducibly probabilistic laws of nature. For the most part, philosophers have neglected to scrutinize Armstrong’s account of probabilistic laws. This is surprising precisely because his own claims about probabilistic laws make it unclear just what he takes them to be. We offer three interpretations of what Armstrong-style probabilistic laws are, and argue that all three interpretations (...) are incompatible either with some feature of Armstrong’s broader metaphysics or with essential features of his account of laws (or both). (shrink)