Considerable hope surrounds the use of disease‐specific pluripotent stem cells to generate models of human disease allowing exploration of pathological mechanisms and search for new treatments. Disease‐specific human embryonic stem cells were the first to provide a useful source for studying certain disease states. The recent demonstration that human somatic cells, derived from readily accessible tissue such as skin or blood, can be converted to embryonic‐like induced pluripotent stem cells (hiPSCs) has opened new perspectives for modelling and understanding a larger (...) number of human pathologies. In this review, we examine the opportunities and challenges for the use of disease‐specific pluripotent stem cells in disease modelling and drug screening. Progress in these areas will substantially accelerate effective application of disease‐specific human pluripotent stem cells for drug screening. (shrink)

In this series of articles, several new hypotheses on sleep and dreaming are presented. In each case, we feel the data do not adequately support the hypothesis. In their lengthy discourse, Hobson et al. represent to us the familiar reciprocal interaction model dressed in new clothes, but expanded beyond reasonable testability. Vertes & Eastman have proposed that REM sleep is not involved in memory consolidation. However, we do not find their arguments persuasive in that limited differences in activity in REM (...) and waking do not lend credence to the idea that memory consolidation occurs in one state and not the other. Solms makes an argument that dreams are generated from the dopaminergic forebrain based largely on pathological lesion studies in humans. We recognize that this argument has some intuitive appeal and agree with some of the tenets but we do not feel that the arguments are completely convincing due to the lack of anatomical controls, including symmetry and laterality. On the whole, there are interesting arguments put forward in these target articles but the evidence does not convince us that new vistas are opened. No Holy Grail of sleep here! [Hobson et al.; Solms; Vertes & Eastman]. (shrink)

Over the last decade, businesses, policymakers, and researchers alike have advocated the need for value creation through inter-organizational collaboration. Researchers have widely argued that organizations that are engaged in collaborative processes create value. Because researchers have tended to focus on the identification of organizational motivations and on key success factors for collaboration, however, both the nature and processes of value creation in inter-organizational collaboration have yet to be examined. A recent theory by Austin and Seitanidi :726–758, 2012a; Nonprofit Volunt Sect (...) Q 41:929–968, 2012b) has proposed an analytical framework for analyzing value creation in inter-organizational collaboration, based on four types of value. The purpose of this current study is to empirically test this framework, and to provide key pointers for analyzing the nature of value, particularly in relation to learning. Our detailed empirical research is based on a 6-year retrospective case study of an inter-organizational partnership within an international development project for local economic development in Guatemala. The study’s contributions are twofold. First, it provides evidence of the critical path of the creation of diverse types of values in a collaborative process; second, it links the different types of value creation with the types of learning that occur in an inter-organizational process. (shrink)

Is morality rational? In this book Gauthier argues that moral principles are principles of rational choice. He proposes a principle whereby choice is made on an agreed basis of cooperation, rather than according to what would give an individual the greatest expectation of value. He shows that such a principle not only ensures mutual benefit and fairness, thus satisfying the standards of morality, but also that each person may actually expect greater utility by adhering to morality, even though the (...) choice did not have that end primarily in view. In resolving what may appear to be a paradox, the author establishes morals on the firm foundation of reason. Gauthier's argument includes an account of value, linking it to preference and utility; a discussion of the curcumstances in which morality is unnecessary; and an application of morals by agreement to relations between peoples at different levels of development and different generations. Finally, he reflects on the assumptions about individuality and community made by his account of rationality and morality. (shrink)

Over the last decade, businesses, policymakers, and researchers alike have advocated the need for value creation through inter-organizational collaboration. Researchers have widely argued that organizations that are engaged in collaborative processes create value. Because researchers have tended to focus on the identification of organizational motivations and on key success factors for collaboration, however, both the nature and processes of value creation in inter-organizational collaboration have yet to be examined. A recent theory by Austin and Seitanidi :726–758, 2012a; Nonprofit Volunt Sect (...) Q 41:929–968, 2012b) has proposed an analytical framework for analyzing value creation in inter-organizational collaboration, based on four types of value. The purpose of this current study is to empirically test this framework, and to provide key pointers for analyzing the nature of value, particularly in relation to learning. Our detailed empirical research is based on a 6-year retrospective case study of an inter-organizational partnership within an international development project for local economic development in Guatemala. The study’s contributions are twofold. First, it provides evidence of the critical path of the creation of diverse types of values in a collaborative process; second, it links the different types of value creation with the types of learning that occur in an inter-organizational process. (shrink)

This article makes a contribution to interface criticism through the notion of chrono-design: the deliberate shaping of experiences of temporality and time through contemporary software techniques and digital technologies. This notion is articulated through discussions of network optimisation, user experience design, behavioural tracking, Hansen’s work on 21st-century media and Hayles’ framework of cognitive assemblages. In particular, the argument considers how contemporary user interfaces complicate conventional notions of the rational, self-reflexive subject by operating beyond consciousness at vast environmental dimensions and accelerated (...) micro-temporal speeds. These conditions, we argue, provide opportunities for new forms of behavioural suspense and captivation best exemplified through the figure of the trap. The politics and aesthetics of captivation, accordingly, should be considered as central to any expanded ecology of cognition. The article then concludes with a short demonstration of experimental uses of chrono-design methods applied critically to political economies of user tracking and data capture as a prompt for further interdisciplinary applied research in this domain. (shrink)

While Dicer plays an important antiviral role through the RNAi pathway in plants and invertebrates, its contribution to antiviral immunity in vertebrates and more specifically mammals is more controversial. The apparent limited RNAi activity in mammalian cells has been attributed to the reduced long dsRNA processive activity of mammalian Dicer, as well as a functional incompatibility between the RNAi and IFN pathways. Why Dicer has lost this antiviral activity in the profit of the IFN pathway is still unclear. We propose (...) that the primary direct antiviral activity of Dicer has been functionally replaced by other sensors in the IFN pathway, leading to its specialization toward microRNA maturation. As a result, Dicer can regulate the innate immune response and prevent basal activation of the IFN pathway in mammals. Here, we discuss this hypothesis, highlighting how the adaptation of the helicase domain of mammalian Dicer may be key to this process. (shrink)

Objective: The aim of the study was to identify clinical variables associated with changes in specific domains of self-reported depression during treatment by antidepressant and/or repetitive Transcranial Magnetic Stimulation in patients with Major Depressive Disorder.Methods: Data from a trial involving 170 patients with MDD receiving either venlafaxine, rTMS or both were re-analyzed. Depressive symptoms were assessed each week during the 2 to 6 weeks of treatment with the 13-item Beck Depression Inventory. Associations between depression changes on BDI13 domains, treatment arm, (...) time, and clinical variables were tested in a mixed linear model.Results: A significant decrease of self-reported depressive symptoms was observed over time. The main characteristics associated with persistent higher depressive symptomatology on Negative Self-Reference domain of the BDI13 were personality disorders, a past history of suicide attempt, age under 65 years old, and female sex.Conclusions: Early cognitive intervention targeting specifically negative self-referencing process could be considered during pharmacological or rTMS treatment for patients with personality disorders and past history of suicide attempt. (shrink)

This article contributes to the development of a professional responsibility theory of public relations ethics. Toward that end, we examine the roles of a public relations practitioner as a professional, an institutional advocate, and the public conscience of institutions served. In the article, we review previously suggested theories of public relations ethics and propose a new theory based on the public relations professional's dual obligations to serve client organizations and the public interest.

In lieu of an abstract, here is a brief excerpt of the content:Artificial Virtues and the Sensible Knave1 David Gauthier Hume's account in the Treatise ofthe artificial virtues, their obligation and motivation, resists easy interpretation. Two passages, taken from his discussion of promises, will introduce, the problems I propose to examine. First: No action can be requir'd of us as our duty, unless there be implanted in human nature some actuating passion or motive, capable of producing the action. This (...) motive cannot be the sense of duty. A sense of duty supposes an antecedent obligation: And where an action is not requir'd by any natural passion, it cannot be requir'd by any natural obligation; since it may be omitted without proving any defect or imperfection in the mind and temper, and consequently without any vice. Now 'tis evident we have no motive leading us to the performance of promises, distinct from a sense of duty. If we thought, that promises had no moral obligation, we never shou'd feel any inclination to observe them.... But as there is naturally no inclination to observe promises, distinct from a sense of their obligation; it follows, that fidelity is no natural virtue, and that promises have no force, antecedent to human conventions.2 Ignore for the present the last sentence quoted. Hume seems clearly to be claiming that (1) an action can be a duty only if there is some motive to perform it other than a sense of duty, and (2) there is no motive to perform an act of promise-keeping other than a sense of duty. From (1) and (2) we may infer that (3) an act of promise-keeping can not be a duty. But since the sense of duty motivates an action only ifit is apprehended to be a duty, then from (2) and (3) we may conclude that (4) there is no motive to perform an act of promise-keeping that does not involve the mistaken apprehension that it is a duty. And the second passage: Afterwards a sentiment of morals concurs with interest, and becomes a new obligation upon mankind.... The difficulties, Volume XVIII Number 2 401 DAVID GAUTHIER that occur to us, in supposing a moral obligation to attend promises, we either surmount or elude. For instance; the expression of a resolution is not commonly suppos'd to be obligatory; and we cannot readily conceive how the making use of a certain form of words shou'd be able to cause any material difference. Here, therefore, we feign a new act ofthe mind, which we call the willing an obligation; and on this we suppose the morality to depend. But we have prov'd already, that there is no such act of the mind, and consequently that promises impose no natural obligation. (T 523) This time, ignore for the present the first sentence. The remainder would seem to confirm my reading ofthe first passage. Hume claims that (5) there is no natural obligation to perform an act of promise-keeping, but (6) we feign the willing of such an obligation. If, as Hume has claimed in the previous passage, (2) there is no motivation to perform an act ofpromise-keeping other than a sense ofduty, and if obligation and duty may be taken as equivalent, then we may conclude as before that (4) there is no motive to perform an act of promise-keeping that does not involve the mistaken apprehension that it is a duty. In his theory of the artificial virtues and vices, Hume considers "the three fundamental laws ofnature, thatofthestabilityofpossession, of its transference by consent, and of the performance of promises" (T 526). It would seem, from the passages cited, that Hume must suppose that there is no real obligation to keep promises, but only a feigned obligation. And since the reasoning that Hume employs in the first ofthe passages that I have cited is explicitly identified with "that reasoning, which prov'd justice in general to be an artificial virtue" (T 518), it seems clear that he must also suppose that there is no real obligation to uphold stability of possession and its transference by consent—no real obligation to observe the other laws of justice or equity.3... (shrink)

For several decades, David Gauthier has been one of the leading philosophers working on practical rationality and deliberation. This book presents a selection of Gauthier's writings on these topics, all but two of which were written after Morals by Agreement. They represent Gauthier's most important contributions to the theory of practical reason, moving some distance from the view a first presented in Reason and Maximization and developed in a much-reprinted chapter of Morals by Agreement. These essays challenge (...) common misconceptions of Gauthier's revisionist conception of practical rationality, and provide important insights with implications for economic theory. (shrink)

The conception of social relationships as contractual lies at the core of our ideology. Indeed, that core is constituted by the intersection of this conception with the correlative conceptions of human activity as appropriate and of rationality as utility-maximizing. My concern is to clarify this thesis and to enhance its descriptive plausibility as a characterization of our ideology, but to undermine its normative plausibility as ideologically effective.

Towards the ends of their reviews, Annette Baier and Jean Hampton allow, if only momentarily, the real spectres to surface. Baier writes, ‘Gauthier rightly sees the dangers of exploitation and subjection inherent in a kin-based and affection-dependent morality, so purports to try for something totally different. Even if our moral natures cannot recognize themselves in Gauthier’s version of them, the problem that drives the attempt [for an individualist and unsentimental morality] is a real one, and so far, I (...) think, an unsolved one; unsolved for morality as well as for moral theory.’ Hampton writes, ‘Gauthier will point out that anyone who insists that a human being has objective value must develop a theory that will not only justify that claim but also explain what reason one would ever have for respecting this value. I believe this is a challenge one has no choice but to accept, given what the moral facts are.’. (shrink)

Economic man seeks to maximize utility. The rationality of economic man is assumed, and is identified with the aim of utility-maximization. But may rational activity correctly be identified with maximizing activity? The object of this essay is to explore, and in part to answer, this question.This is not an issue solely, or perhaps even primarily, about the presuppositions of economics. The two great modern schools of moral and political thought in the English-speaking world, the contractarian and the utilitarian, identify rationality (...) with maximization, and bring morality into their equations as well. To the contractarian, rational man enters civil society to maximize his expectation of well-being, and morality is that system of principles of action which rational men collectively adopt to maximize their well-being. To the utilitarian, the rational and moral individual seeks the maximum happiness of mankind, with which he identifies his own maximum happiness. (shrink)

In the days when the Great Central and the Midland ran competitive services from Leicester to London, I agreed to meet your train when you came up from Leicester. “It arrives at 12.5”, you said in your letter. But you neglected to mention which station, and only on the morning of your journey did each of us realize that this matter had been left open. You intended to travel from Leicester Central, it being more convenient for you than London Road, (...) and you supposed that I would be able to infer your intention by consulting Bradshaw, and noting a 12.5 arrival from Leicester at Marylebone. (shrink)

Law is the expression of public reason. I want to explicate and justify this assertion, which lies at the core of a normative theory of law. Primarily, I want to focus on the concept of public reason, showing what it is, relating it to private or individual reason, and finding its rationale in that relation. I shall then argue that public reason exhausts the normative space where law may be found. Appealing to public reason, I shall show that the authority (...) that law claims over the judgments and actions of citizens must ultimately be grounded in their own rationality. (shrink)

The intervention ladder, developed by the Nuffield Council on Bioethics, is a framework intended to help evaluate the ethical acceptability and justification of public health interventions according to their intrusion on liberty.1 In their recent article, Paetkau2 argues ‘the ladder obscures potential interventions that operate on a systemic rather than individual level’ (p. 1) and that ‘it is crucial that systemic interventions not be left off the table when considering potential concrete interventions’ (p. 3), leading them to propose instead the (...) ‘intervention stairway’. Yet, in this commentary we argue the intervention ladder does not delimit the sorts of public health interventions that may be considered to address a public health issue, although it may speak to their putative justification. Hence, despite its other considerable shortcomings,3 4 there is no need, as Paetkau argues, to broaden the intervention ladder to include systemic factors. Contrary to Paetkau’s claim, the intervention ladder does not preclude policymakers from considering systemic factors’ impact on health outcomes or the public health interventions and strategies that could be implemented to address them. Paetkau adduces the example of measures to protect patients, healthcare workers and healthcare capacity from the threat of infectious diseases. They argue that certain …. (shrink)

Hobbes on Demonstration and Construction DAVID GAUTHIER 1~ IN 1656 Hobbes published Six Lessons to the Professors of Mathematics, with an Epistle Dedicatory to the Marquis of Dorchester, Lord Pierrepont. In this Epistle, Hobbes distinguishes the demonstrable from the indemonstrable arts: "demonstrable are those the construction of the subject whereof is in the power of the artist himself, who, in his demonstration, does no more but deduce the consequences of his own operation" . Although this passage, with the explication (...) Hobbes offers for it and the consequences he draws from it, and a similar discussion in De homine, published two years later, have not been unnoticed, their significance for Hobbes's account of science in general, and civil philosophy or politics in particular, has not, I think, been I am grateful to the University of East Anglia for appointing me a Visiting Research Fellow during the period in which the first draft of this paper was written. A second draft was presented at the Third Quadrennial International Fellows Conference of the Center for Philosophy of Science at the University of Pittsburgh, sponsored by the Florence Center for the History and Philosophy of Science. I am grateful for the remarks of my commentator, J. E. McGuire, and for the discussion. I am also grateful for the comments of the two referees who read this paper for the Journal of the History of Philosophy. References to Hobbes's works appear as.. (shrink)

Psychologists live in a globalizing world where traditional boundaries are fading and, therefore, increasingly work with persons from diverse cultural backgrounds. The Universal Declaration of Ethical Principles for Psychologists provides a moral framework of universally acceptable ethical principles based on shared human values across cultures. The application of its moral framework in developing codes of ethics and reviewing current codes may help psychologists to respond ethically in a rapidly changing world. In this article, a model is presented to demonstrate how (...) to use the Universal Declaration as a guide for creating or reviewing a code of ethics. This model may assist psychologists in various parts of the world in establishing codes of ethics that will promote global understanding and cooperation while respecting cultural differences. The article describes the steps involved in the application of the model and provides concrete examples as well as several useful comments and suggestions. This guide for the application of the Universal Declaration may also be used for consultation, education, and training relative to the Universal Declaration of Ethical Principles for Psychologists. (shrink)

Current discussion of the normative issues surrounding secession is both helped and hindered by the existence of but one philosophic treatment of these issues sufficiently systematic and comprehensive to qualify as a theory of secession - Allen Buchanan’s. He provides the unique focal point, and so simplifies the task of those who seek to begin from the present state of the art. But in providing the unique focal point, Buchanan complicates the task of those who view, or think they view, (...) secession rather differently than he does. He defends ’a moral right to secede’ but a very qualified right, focusing on state-perpetrated injustice, the preservation of group culture and, in extreme cases, the literal survival of group members. And Buchanan further insists that where preservation of group culture is at stake, ’Neither the state nor any third party has a valid claim to the seceding territory’ -or such a claim is waived so that ’secession in order to preserve a culture is permissible if both parties consent to it’- a condition that he thinks may come to apply to the situation of Quebec. (shrink)

I want to enquire into the relationship between the normative claims of a society and the normative stances of its members. I shall develop a contractarian perspective, as the only one available to persons who may neither expect nor require their fellows to share their own orientation to values and norms. Although I only touch on these matters here, I hope to contribute to an interpretation of the clauses on the establishment and exercise of religion in the First Amendment to (...) the United States constitution, and to suggest guidelines for determining rights and duties in becoming and being a parent. More generally, I offer answers to certain questions about how social practices and institutions may be justified in a democratic society. (shrink)

In his recent paper, “Justice as Fairness: Political not Metaphysical,” John Rawls makes use of a footnote to disown what to many readers must have seemed one of the most striking and original underlying ideas of his theory of justice, that it “is a part, perhaps the most significant part, of the theory of rational choice.” That Rawls should issue this disclaimer indicates, at least in my view, that he has a much clearer understanding of his theory, and its relationship (...) to rational choice than he did at the time that he wrote A Theory of Justice. As I note in Morals by Agreement, Rawls does not show that principles of justice are principles of rational choice. Hence, in appropriating the idea, I can claim diat I am undertaking a pioneering enterprise. No doubt Thomas Hobbes would have undertaken it had the resources of the theory of rational choice been at his disposal, but I do not intend to pursue counterfactuals in a search for historical antecedents. Moral theory as rational choice theory is, I claim, a new venture. (shrink)

Are Hobbes's laws of nature to be understood primarily as theorems of reason, or as commands of God, or as commands of the civil sovereign? Each of these accounts can be given textual support; each identifies a role that the laws may be thought to play. Examining the full range of textual references, discussing the place of the laws of nature in Hobbes's argument, and considering how the laws may be known, give strongest support to the first of the three (...) accounts, that the laws are primarily rational precepts and only secondarily civil and divine commands. (shrink)

Reason, egoism, and utilitarianism, by H. Sidgwick.--Is egoism reasonable? By G. E. Moore.--Ultimate principles and ethical egoism, by B. Medlin.--In defense of egoism, by J. Kalin.--Virtuous affections and self-love, by F. Hutcheson.--Our obligation to virtue, by D. Hume.--Duty and interest, by H. A. Prichard.--The natural condition of mankind and the laws of nature, by T. Hobbes.--Why should we be moral? By K. Baier.--Morality and advantage, by D. P. Gauthier.--Bibliographical essay (p. 181-184).

Lastly, those are not at all to be tolerated who deny the being of a God. Promises, covenants, and oaths, which are the bonds of human society, can have no hold upon an atheist. The taking away of God, though but even in thought, dissolves all.These words, from Locke's Letter Concerning Toleration, ring unconvincingly in our ears. They affirm that the bonds of human society hold only those who believe in God. This affirmation breaks into two propositions: the bonds of (...) human society are promises, covenants, and oaths; promises, covenants, and oaths hold only those who believe in God.Much might be said about the first proposition, but not here. Whether it rings unconvincingly in our ears, surely the second does, and it is this which I shall address. The suppos1t1on that moral conventions depend on religious belief has become alien to our way of thinking. Modern moral philosophers do not meet it with vigorous denials or refutations; usually they ignore it. (shrink)

This is the text of The Lindley Lecture for 1989, given by David Gauthier, a Canadian philosopher.

To sell a new drug, pharmaceutical companies must discover a compound, run clinical trials to test its efficacy and safety, get it approved by regulatory bodies, produce the drug, and market it. As this process brings the drug through so many hands, there are risks of many kinds of corruption. The pharmaceutical industry has recently gone from being one of the most admired industries to being described by the majority of Americans as “dishonest, unethical, and more concerned with profits than (...) with individual and public health.” Legal scholar Marc Rodwin suggested that the pharmaceutical industry can be viewed through the lens of institutional corruption as defined by legal scholar Lawrence Lessig, whereby widespread or systemic practices undermine the main purposes of drug therapy — healing illness, preventing medical problems, and alleviating suffering. Many drugs do serve these goals, yet a significant number of drugs churned out by pharmaceutical companies are ineffective or have dangerous side effects that could have been predicted had the companies conducted the appropriate research. (shrink)

Bringing Hegelian texts into a critical dialogue with the work of a number of important feminists, h.