The gelsolin gene family encodes a number of higher eukaryotic actin-binding proteins that are thought to function in the cytoplasm by severing, capping, nucleating or bundling actin filaments. Recent evidence, however, suggests that several members of the gelsolin family may have adopted unexpected nuclear functions including a role in regulating transcription. In particular, flightless I, supervillin and gelsolin itself have roles as coactivators for nuclear receptors, despite the fact that their divergence appears to predate the evolutionary appearance of nuclear receptors. (...) Flightless I has been shown to bind both actin and the actin-related BAF53a protein, which are subunits of SWI/SNF-like chromatin remodelling complexes. The primary sequences of some actin-related proteins such as BAF53a exhibit conservation of residues that, in actin itself, are known to interact with gelsolin-related proteins. In summary, there is a growing body of evidence supporting a biological role in the nucleus for actin, Arps and actin-binding proteins and, in particular, the gelsolin family of actin-binding proteins. (c) 2005 Wiley Periodicals, Inc. (shrink)

Randomized controlled trial trial designs exist on an explanatory-pragmatic spectrum, depending on the degree to which a study aims to address a question of efficacy or effectiveness. As conceptualized by Schwartz and Lellouch in 1967, an explanatory approach to trial design emphasizes hypothesis testing about the mechanisms of action of treatments under ideal conditions, whereas a pragmatic approach emphasizes testing effectiveness of two or more available treatments in real-world conditions. Interest in, and the number of, pragmatic trials has grown substantially (...) in recent years, with increased recognition by funders and stakeholders worldwide of the need for credible evidence to inform clinical decision-making. This increase has been accompanied by the onset of learning healthcare systems, as well as an increasing focus on patient-oriented research. However, pragmatic trials have ethical challenges that have not yet been identified or adequately characterized. The present study aims to explore the views of key stakeholders with respect to ethical issues raised by the design and conduct of pragmatic trials. It is embedded within a large, four-year project that seeks to develop guidance for the ethical design and conduct of pragmatic trials. As a first step, this study will address important gaps in the current empirical literature with respect to identifying a comprehensive range of ethical issues arising from the design and conduct of pragmatic trials. By opening up a broad range of topics for consideration within our parallel ethical analysis, we will extend the current debate, which has largely emphasized issues of consent, to the range of ethical considerations that may flow from specific design choices. Semi-structured interviews with key stakeholders, across multiple jurisdictions, identified based on their known experience and/or expertise with pragmatic trials. We expect that the study outputs will be of interest to a wide range of knowledge users including trialists, ethicists, research ethics committees, journal editors, regulators, healthcare policymakers, research funders and patient groups. All publications will adhere to the Tri-Agency Open Access Policy on Publications. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:IntroductionStuart J. Youngner (bio), Laura A. Siminoff (bio), and Renie Schapiro (bio)This issue of the Kennedy Institute of Ethics Journal (KIEJ) centers on a piece of empirical research. The motivation behind the study of Laura Siminoff, Christopher Burant, and Stuart Youngner (2004) was to find out more about what the general public understands and believes about when a person is dead. More specifically, the study tried to determine (...) how members of the public define death, especially their acceptance and interpretation of the medical concept of "brain death," and their attitudes toward the so-called "dead donor rule," an informal but powerful social and legal norm insisting that the taking of organs for transplantation not cause the death of the source of those organs.As the demand for organs increases and the waiting list grows, the United States has explored multiple ways to expand the pool of potential donors. One approach has been to gerrymander (coherently or not) the line between life and death to shift patients who are extremely compromised but traditionally considered to be in the living category into the dead category. In this way, the dead donor rule remains technically intact. This reasoning is explicit in the report of the Harvard Medical School Ad Hoc Committee (1968) that "introduced" "brain death" to the American culture. Since then, other efforts to redraw the line have been proposed and rejected.One alternative to gerrymandering is to consider under what conditions, if any, it is morally acceptable to violate the dead donor rule. Some would argue that this alternative is the more "honest" approach. Rather than sidestepping moral problems by calling people dead, it brings the moral problems to the surface where the necessity of sticking to the rule can be considered on its own merits. However, when the Journal of the American Medical Association printed a position paper that proposed making anencepahlic newborns an exception to the dead donor rule, along with arguments about why this was acceptable, the outcry was so great that the proposal was retracted (AMA 1995).Clearly, our society has identified organ transplantation as a priority, although two papers in this volume (those by Courtney Campbell and by Megan Crowley-Matoka and Robert Arnold) take issue with that prioritization. The fact that the donor pool has remained relatively stable (and inadequate) despite massive efforts [End Page 211] to increase it speaks, at least in part, to the cultural and legal resistance to "new" ways to procure more organs. Voluntarism seems to have peaked. Financial incentives clash with the heavily endorsed notion of the "gift of life" and seem to many to violate the dignity of the human body. Presumed consent or eminent domain, in which the community has a greater claim to a person's organs than that person or his/her family, go against the grain of American individual freedom and the ethos of patient autonomy.Abandoning the dead donor rule generally is regarded as an even tougher sell to the American public and its legislators. The study by Siminoff and colleagues attempts, among other things, to gauge just how tough this sell would be. What the data actually demonstrate is a matter of interpretation, and this issue of the KIEJ is devoted to some of those interpretations. The authors, with the exception of Daniel Hausman, came together for a meeting in Cleveland, Ohio, during which the study's methods and data were presented with time for questions, clarifications, and general discussion. The authors then worked with the editors to generate the papers printed in this volume.The issue begins with a presentation of the study conducted by Siminoff and colleagues. The same paper also appears in the journal Social Science and Medicine, where it includes the conclusions of the authors (Siminoff, Burant, and Youngner 2004). In the current volume, we present only the methodology of and data from the study, allowing a number of distinguished commentators to offer their own conclusions and reflections.The first response comes from Tracy Schmidt, Executive Director of Intermountain Donor Services, one of our nation's organ procurement organizations (OPOs). For years, organ procurement professionals have reported anecdotal stories about families who wished to donate organs of... (shrink)

We take rights to be fundamental to everyday life. Rights are also controversial and hotly debated both in theory and practice. Where do rights come from? Are they invented or discovered? What sort of rights are there and who is entitled to them? In this comprehensive introduction, Tom Campbell introduces and critically examines the key philosophical debates about rights. The first part of the book covers historical and contemporary theories of rights, including the origin and variety of rights and (...) standard justifications of them. He considers challenges to rights from philosophers such as Bentham, Burke and Marx. He also examines different theories of rights, such as natural law, social contract, utilitarian and communitarian theories of rights and the philosophers and political theorists associated with them, such as John Stuart Mill, John Rawls, Robert Nozick and Michael Sandel. The second part of the book explores the role of rights-promoting institutions and critically assesses legal rights and international human rights, including the United Nations. The final part of the book examines how philosophies of rights can be applied to freedom of speech, issues of social welfare and the question of self-determination for certain groups or peoples. _Rights: A Critical Introduction_ is essential reading for anyone new to the subject of rights and any student of political philosophy, politics and law. (shrink)

This book is a thoroughgoing analysis, interpretation, and defense of John Stuart Mill's proof of the principle of utility. It answers the traditional charges levelled against that proof, supports a comprehensive interpretation by painstaking study of Mill's text in Utilitarianism , and marshals arguments on behalf of utility as the first principle of morality. Universal Justice is dedicated to the advancement of justice conceived globally. It publishes interpretations of the history of thought as well as original monographs and collective (...) volumes, including work related to the activities of the International Society for Universalism. (shrink)

The debate over teaching Darwin's theory in public schools has been a feature of American public life since at least the Scopes trial of 1925. Drawing on the liberal arts tradition centered in rhetoric and civic argument, this essay argues that science education should not merely prepare tomorrow's scientists, but also educate scientifically articulate citzens. It offers the Origin of Species as a model for educational strategies that would protect the integrity of science, while addressing the objections of students and (...) their parents to Darwin's ideas. Darwin's work belongs in the great tradition of two-sided humanistic argument central to Western education since antiquity, and exemplified in John Milton and John Stuart Mitt. Debate between Darwin's theory and its alternatives, whether young earth creationism or Intelligent Design, is recommended as a means to teach Darwin's theory and train students in the central role of critique and argument in scientific reasoning. (shrink)

Whilst this paper was initially part of a larger project tracing the development of Anglo-American thought from the colonial through to the post-colonial era, below it stands alone as reflection on the colonialism of John Stuart Mill read from a post-colonial perspective. It aims to show that Mill's views on colonial rule were largely informed by his principle of liberty which, in turn, was based on his qualitative utilitarianism. The driving force behind his colonialism, as with his work in (...) general, was his unwavering belief in the importance of human progress and development. Mill never believed, as did many of his contemporaries, that the ‘backward’ societies of the colonies were inherently inferior, but rather that they needed paternal intervention from more civilised, progressive societies in order to stimulate growth in that spontaneous human development was not inevitable. When read in this light Mill's views on colonial rule, while culturally bigoted and ethnocentric, appear less contradictory to his liberalism as a whole. (shrink)

The criticism that voluntary codes of conduct are ineffective can be met by giving greater centrality to human rights in such codes. Provided the human rights obligations of multinational corporations are interpreted as moral obligations specifically tailored to the situation of multinational corporations, this could serve to bring powerful moral force to bear on MNCs and could provide a legitimating basis for NGO monitoring and persuasion. Approached in this way the human rights obligations of MNCs can be taken to include (...) support for political as well as economic rights. This will go some way towards filling the regulatory gap created by the difficulty of controlling the activities of corporations operating globally. However, such a proposal will require a measure of ‘meta-regulation’ whereby the operations of MNCs are legally required to be sufficiently transparent to create the conditions for effective external moral scrutiny. (shrink)

In this book of essays, he argues that morality cannot be defined solely by rational and universal principles; instead, a major place must be found for changing and conflicting ideals, values peculiar to specific times and cultures.

Science and the originality of life -- Christian facticity -- Grasping life as a topic -- Ruinance -- The retrieval of history -- Facticity and ontology -- Factical speaking -- Rhetoric -- Sophistry.

In this book, Stuart Hampshire argues that no individual and no modern society can avoid conflicts between incompatible moral interests.

Ethical descriptivism is the view that all ethical properties are descriptive properties. Frank Jackson has proposed an argument for this view which begins with the premise that the ethical supervenes on the descriptive, any worlds that differ ethically must differ also descriptively. This paper observes that Jackson's argument has a curious structure, taking a linguistic detour between metaphysical starting and ending points, and raises some worries stemming from this. It then proposes an improved version of the argument, which avoids these (...) worries, and responds to some potential objections to this version of the argument. (shrink)

The philosopher John J. McDermott comes out of the long American tradition that takes the aim of philosophical inquiry to be interpretation of the open meanings of experience, so that we might all live fuller and richer lives. Here, the authors of these nine essays explore his highly original interpretations of philosophy's various questions about our shared existence. How are we to understand the nature of American culture and to carry forward its important contributions? What is the personal importance of (...) embodiment, of living in the realization of death? How does our physical and personal environment nourish bodies and spirits? What does the deliberate pursuit of a morality offer us? How can we carry forward the fundamental tasks of education to enable those who follow us to use our shared past to address their civic and spiritual problems? What are the possibilities for community? Together, these essays offer a clear, multi-layered understanding of the compelling vision that McDermott has presented over the years. In an Afterword, McDermott responds to the authors' queries and concerns, offering a restatement of his understanding of the American philosopher's task. These essays indicate, and McDermott's response confirms, that for him philosophy is not a purely cerebral activity. Philosophy is, rather, an intellectual means of exploring the fullness of human experience, and it functions best when it operates in the context of the broad sweep of the humanities. Similarly, for McDermott the self is no given substantial entity. On the contrary, it is relational, rooted geographically and socially in its place and its fellows, and damaged when these life-giving processes fail. Further, McDermott does not accept any ultimate canopy of meaning. The human journey is a personal project within which provisional meanings must be created to sustain our advance. (shrink)

The Second World War put an end to America's historical isolationism. Three American thinkers -- Reinhold Niebuhr, Hans Morgenthau, and Kenneth Waltz -- developed a modern strategic framework that sought to introduce Americans to the harsher realities of international politics. Yet even as the United States began to embrace this new Realism, atomic weaponry threatened to make it absurd. This engrossing story of how the three chief architects of a powerful ideology struggled with the implications of their own creation offers (...) crucial context for contemporary debates about the resort to war and weapons of mass destruction. (shrink)

Fetal pain has long been a contentious issue, in large part because fetal pain is often cited as a reason to restrict access to termination of pregnancy or abortion. We have divergent views regarding the morality of abortion, but have come together to address the evidence for fetal pain. Most reports on the possibility of fetal pain have focused on developmental neuroscience. Reports often suggest that the cortex and intact thalamocortical tracts are necessary for pain experience. Given that the cortex (...) only becomes functional and the tracts only develop after 24 weeks, many reports rule out fetal pain until the final trimester. Here, more recent evidence calling into question the necessity of the cortex for pain and demonstrating functional thalamic connectivity into the subplate is used to argue that the neuroscience cannot definitively rule out fetal pain before 24 weeks. We consider the possibility that the mere experience of pain, without the capacity for self reflection, is morally significant. We believe that fetal pain does not have to be equivalent to a mature adult human experience to matter morally, and so fetal pain might be considered as part of a humane approach to abortion. (shrink)

In Better Never to Have Been, David Benatar argues that existence is always a harm. His argument, in brief, is that this follows from a theory of personal good which we ought to accept because it best explains several ‘asymmetries’. I shall argue here that Benatar's theory suffers from a defect which was already widely known to afflict similar theories, and that the main asymmetry he discusses is better explained in a way which allows that existence is often not a (...) harm. (shrink)

Taking a fundamentally critical approach to the subject of business ethics, this book deals with the traditional material of ethics in business, as well as introducing and surveying some of the most interesting developments in critical ethical theory which have not yet been introduced to the mainstream. Including chapters on different philosophical approaches to ethics, this is a highly structured and clearly written textbook, the first book of its kind on this often neglected aspect of business.

There is no strong reason to believe that human-level intelligence represents an upper limit of the capacity of artificial intelligence, should it be realized. This poses serious safety issues, since a superintelligent system would have great power to direct the future according to its possibly flawed motivation system. Solving this issue in general has proven to be considerably harder than expected. This paper looks at one particular approach, Oracle AI. An Oracle AI is an AI that does not act in (...) the world except by answering questions. Even this narrow approach presents considerable challenges. In this paper, we analyse and critique various methods of controlling the AI. In general an Oracle AI might be safer than unrestricted AI, but still remains potentially dangerous. (shrink)

When philosophers discuss the possibility of machines making scientific discoveries, they typically focus on discoveries in physics, biology, chemistry and mathematics. Observing the rapid increase of computer-use in science, however, it becomes natural to ask whether there are any scientific domains out of reach for machine discovery. For example, could machines also make discoveries in qualitative social science? Is there something about humans that makes us uniquely suited to studying humans? Is there something about machines that would bar them from (...) such activity? A close look at the methodology of interpretive social science reveals several abilities necessary to make a social scientific discovery, and one capacity necessary to possess any of them is imagination. For machines to make discoveries in social science, therefore, they must possess imagination algorithms. (shrink)

Campbell Brown is one of the most recent additions to our faculty. We thought we’d welcome him to the Department with some questions.

Despite tendencies to compete for a prime place in moral theory, neither virtue ethics nor the four principles approach should claim to be superior to, or logically prior to, the other. Together they provide a more adequate account of the moral life than either can offer on its own. The virtues of principlism are clarity, simplicity and (to some extent) universality. These are well illustrated by Ranaan Gillon’s masterly analysis of the cases he has provided. But the vices of this (...) approach are the converse of its virtues: neglect of emotional and personal factors, oversimplification of the issues, and excessive claims to universality. Virtue ethics offers a complementary approach, providing insights into moral character, offering a blend of reason and emotion, and paying attention to the context of decisions. The cases provided can be more adequately understood if we combine the approaches. Both should foster the virtues of humility and magnanimity. (shrink)

Michel Foucault's The Archaeology of Knowledge was published in March 1969; Discipline and Punish in February 1975. Although only six years apart, the difference in tone is stark: the former is a methodological treatise, the latter a call to arms. What accounts for the radical shift in Foucault's approach? Foucault's time in Tunisia had been a political awakening for him, and he returned to a France much changed by the turmoil of 1968. He taught at the experimental University of Vincennes (...) and then moved to a prestigious position at the Collège de France. He quickly became involved in activist work concerning prisons and health issues such as abortion rights, and in his seminars he built research teams to conduct collaborative work, often around issues related to his lectures and activism. Foucault: The Birth of Power makes use of a range of archival material, including newly available documents at the Bibliothèque nationale de France, to provide a detailed intellectual history of Foucault as writer, researcher, lecturer and activist. Through a careful reconstruction of Foucault's work and preoccupations, Elden shows that, while Discipline and Punish may be the major published output of this period, it rests on a much wider range of concerns and projects. (shrink)

This volume argues for a new image of science that understands both natural and social phenomena to be the product of mechanisms, casting the work of science as an effort to understand those mechanisms. Glennan offers an account of the nature of mechanisms and of the models used to represent them in physical, life, and social sciences.

Ethicists and economists commonly assume that if A is all things considered better than B, and B is all things considered better than C, then A is all things considered better than C. Call this principle Transitivity. Although it has great conceptual, intuitive, and empirical appeal, I argue against it. Larry S. Temkin explains how three types of ethical principle, which cannot be dismissed a priori, threaten Transitivity: (a) principles implying that in some cases different factors are relevant to comparing (...) A to C than to comparing A to B or B to C; (b) principles of limited scope; (c) principles implying that morally relevant differences in degree can amount to differences in kind. My counterexamples employ a principle of type (c): pleasures and pains enormously different in intensity differ in kind. Temkin has also endorsed this type of counterexample, using arguments based on earlier drafts of this paper. (shrink)

While philosophers hold that it is patently absurd to blame robots or hold them morally responsible [1], a series of recent empirical studies suggest that people do ascribe blame to AI systems and robots in certain contexts [2]. This is disconcerting: Blame might be shifted from the owners, users or designers of AI systems to the systems themselves, leading to the diminished accountability of the responsible human agents [3]. In this paper, we explore one of the potential underlying reasons for (...) robot blame, namely the folk's willingness to ascribe inculpating mental states or "mens rea" to robots. In a vignette-based experiment (N=513), we presented participants with a situation in which an agent knowingly runs the risk of bringing about substantial harm. We manipulated agent type (human v. group agent v. AI-driven robot) and outcome (neutral v. bad), and measured both moral judgment (wrongness of the action and blameworthiness of the agent) and mental states attributed to the agent (recklessness and the desire to inflict harm). We found that (i) judgments of wrongness and blame were relatively similar across agent types, possibly because (ii) attributions of mental states were, as suspected, similar across agent types. This raised the question - also explored in the experiment - whether people attribute knowledge and desire to robots in a merely metaphorical way (e.g., the robot "knew" rather than really knew). However, (iii), according to our data people were unwilling to downgrade to mens rea in a merely metaphorical sense when given the chance. Finally, (iv), we report a surprising and novel finding, which we call the inverse outcome effect on robot blame: People were less willing to blame artificial agents for bad outcomes than for neutral outcomes. This suggests that they are implicitly aware of the dangers of overattributing blame to robots when harm comes to pass, such as inappropriately letting the responsible human agent off the moral hook. (shrink)

The ‘No Ought From Is’ principle (or ‘NOFI’) states that a valid argument cannot have both an ethical conclusion and non-ethical premises. Arthur Prior proposed several well-known counterexamples, including the following: Tea-drinking is common in England; therefore, either tea-drinking is common in England or all New Zealanders ought to be shot. My aim in this paper is to defend NOFI against Prior’s counterexamples. I propose two novel interpretations of NOFI and prove that both are true.

The philosopher John J. McDermott comes out of the long American tradition that takes the aim of philosophical inquiry to be interpretation of the open meanings of experience, so that we might all live fuller and richer lives. Here, the authors of these nine essays explore his highly original interpretations of philosophy's various questions about our shared existence. How are we to understand the nature of American culture and to carry forward its important contributions? What is the personal importance of (...) embodiment, of living in the realization of death? How does our physical and personal environment nourish bodies and spirits? What does the deliberate pursuit of a morality offer us? How can we carry forward the fundamental tasks of education to enable those who follow us to use our shared past to address their civic and spiritual problems? What are the possibilities for community? Together, these essays offer a clear, multi-layered understanding of the compelling vision that McDermott has presented over the years. In an Afterword, McDermott responds to the authors' queries and concerns, offering a restatement of his understanding of the American philosopher's task. These essays indicate, and McDermott's response confirms, that for him philosophy is not a purely cerebral activity. Philosophy is, rather, an intellectual means of exploring the fullness of human experience, and it functions best when it operates in the context of the broad sweep of the humanities. Similarly, for McDermott the self is no given substantial entity. On the contrary, it is relational, rooted geographically and socially in its place and its fellows, and damaged when these life-giving processes fail. Further, McDermott does not accept any ultimate canopy of meaning. The human journey is a personal project within which provisional meanings must be created to sustain our advance. (shrink)