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.

On 26 August 1974, Michel Foucault completed work on Discipline and Punish, and on that very same day began writing the first volume of The History of Sexuality. A little under ten years later, on 25 June 1984, shortly after the second and third volumes were published, he was dead. This decade is one of the most fascinating of his career. It begins with the initiation of the sexuality project, and ends with its enforced and premature closure. Yet in 1974 (...) he had something very different in mind for The History of Sexuality than the way things were left in 1984. Foucault originally planned a thematically organised series of six volumes, but wrote little of what he promised and published none of them. Instead over the course of the next decade he took his work in very different directions, studying, lecturing and writing about historical periods stretching back to antiquity. This book offers a detailed intellectual history of both the abandoned thematic project and the more properly historical version left incomplete at his death. It draws on all Foucault’s writings in this period, his courses at the Collège de France and lectures elsewhere, as well as material archived in France and California to provide a comprehensive overview and synthetic account of Foucault’s last decade. (shrink)

William James has long been recognized as a central figure in the American philosophic tradition, and his ideas continue to play a significant role in contemporary thinking. Yet there has never been a comprehensive exploration of the thought of this seminal philosopher and psychologist. In Experiencing William James, renowned scholar James Campbell provides the fuller and more complete analysis that James scholarship has long needed. Commentators typically address only pieces of James's thought or aspects of his vision, often in (...) an attempt to make the task of understanding James seem easier than it is or else to dismiss him as a philosophically unprepared if well-meaning amateur. The isolated nature of these examinations, too often divorced from the original contexts, badly hinders and even distorts their conclusions. Focusing on James's own ideas rather than his critiques of others, and drawing from a wealth of scholarship that includes the completed editions of his writings and correspondence, Experiencing William James provides an invaluable, comprehensive view of James as he participates in and advances the pragmatic spirit that is at the core of American philosophy. Taking the whole of the man's thinking into account, this book offers the richest perspective so far on this great but not fully comprehended intellectual. (shrink)

What role does the imagination play in scientific progress? After examining several studies in cognitive science, I argue that one thing the imagination does is help to increase scientific understanding, which is itself indispensable for scientific progress. Then, I sketch a transcendental justification of the role of imagination in this process.

The last three decades have witnessed a heated debate of the merits of intelligent design (ID) as a way to understand a number of observable natural phenomena. The present dispute has its roots in a much older discussion: that of natural theology, which has always had as its goal the discernment of design(s) attributable to God in the natural world. Despite its ongoing relevance, natural theology does not have a coherent scholarly history. Turning Points in Natural Theology from Bacon to (...) Darwin deftly fills that gap, analysing the argument of design during the period from Francis Bacon (1561-1626) to Charles Darwin (1809-82), with a specific focus on those moments at which the rhetorical terms changed significantly. (shrink)

I claim that one way thought experiments contribute to scientific progress is by increasing scientific understanding. Understanding does not have a currently accepted characterization in the philosophical literature, but I argue that we already have ways to test for it. For instance, current pedagogical practice often requires that students demonstrate being in either or both of the following two states: 1) Having grasped the meaning of some relevant theory, concept, law or model, 2) Being able to apply that theory, concept, (...) law or model fruitfully to new instances. Three thought experiments are presented which have been important historically in helping us pass these tests, and two others that cause us to fail. Then I use this operationalization of understanding to clarify the relationships between scientific thought experiments, the understanding they produce, and the progress they enable. I conclude that while no specific instance of understanding (thus conceived) is necessary for scientific progress, understanding in general is. (shrink)

Every action, touch, utterance, and look, every listening, taste, smell, and feel is a living question; but it is no ordinary propositional one-by-one question, rather it is a plenisentient sensing and probing non-propositional enquiry about how our world is, in its present continuous sense, and in relation to how we anticipate its becoming. I will take this assumption as my first premise and, by using the notion of enkinaesthesia, I will explore the ways in which an agent’s affectively-saturated co-engagement with (...) its world establishes patterns of co-articulation of meaning within the anticipatory affective dynamics and the experiential entanglement necessary for expedient action and adaptation. In advancing this thesis I will reject the minimalist notions of embodiment by amplifying and extending the claims made by the most radical of the embodied mind theories. Crucially, I will offer a new wave of embodiment theory which has at its core the radical extension of sensorimotor affect into the life and being of other agents where their experience is for us both direct and immediate. This I will present as an immanent intercorporeality. (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)

1. Animal Cruelty Industrial farming is appallingly abusive to animals. Pigs. In America, nine-tenths of pregnant sows live in “gestation crates. ” These pens are so small that the animals can barely move. When the sows are first crated, they may flail around, in an attempt to get out. But soon they give up. Crated pigs often show signs of depression: they engage meaningless, repetitive behavior, like chewing the air or biting the bars of the stall. The sows live like (...) this for four months. Gestation crates will be phased out in Europe by the end of 2012, but they will still be used in America.1 In nature, pigs nurse their young for about thirteen weeks. But in industrial farms, piglets are taken from their mothers after about ten days. Because the piglets are weaned prematurely, they develop a lifelong craving to suck and chew. But the farmers don’t want them sucking and chewing on other pigs’ tails. So the growers routinely snip off the tails of all their pigs. They do this with a pair of pliers and no anesthetic. However, the whole tail is not removed; a tender stump remains. The point is to render the area sensitive, so the pigs being chewed on will fight back. Which they do.2 Over 113 million pigs are slaughtered each year in America.3 Typically, these pigs are castrated, their needle teeth are clipped, and one of their ears is notched for identification —all without pain relief.4 In nature, pigs spend up to three quarters of their waking hours foraging and exploring their environment.5 But in the factory farms, “tens of thousands of hogs spend their entire lives ignorant of earth or straw or sunshine, crowded together beneath a metal roof standing on metal slats suspended over a septic tank. ”6 Bored, and in constant pain, the pigs must perpetually inhale the fumes of their own waste. These pigs often get sick, and their ill health is exacerbated by the overcrowding. In 2000, the U.S. Department of Agriculture compared hog farms containing over 10,000 pigs—which is the norm—with farms containing under 2,000 pigs. (shrink)

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 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.

“Descartes on Spontaneity, Indifference, and Alternatives” This essay argues for a “two‐way” compatibilist reading of Descartes on the topic of free will, i.e., Descartes holds that free will is compatible with determinism, and yet also thinks that free will requires a two‐way power to pursue or avoid, and affirm or deny.

Ever since the publication of 'Truth' in 1959 Sir Michael Dummett has been acknowledged as one of the most profoundly creative and influential of contemporary philosophers. His contributions to the philosophy of thought and language, logic, the philosophy of mathematics, and metaphysics have set the terms of some of most fruitful discussions in philosophy. His work on Frege stands unparalleled, both as landmark in the history of philosophy and as a deep reflection on the defining commitments of the analytic school. (...) This volume of specially composed essays on Dummett's philosophy presents a new perspective on his achievements, and provides a focus for further research fully informed by the Dummett's most recent publications. Collectively the essays in philosophy of mathematics provide the most sustained discussion to date of the role of Dummett's diagnosis of the root of the logico-mathematical paradoxes in his case for an intuitionist revision of classical mathematics. The themes of other essays include a fundamental challenge to Dummett's Fregean understanding of predication, and a criticism of his case for logical revision outside of mathematics. (shrink)

Humans are moral creatures. Among all life on Earth, we alone experience rich moral emotions, follow complex rules governing how we treat one another, and engage in moral dialogue. But how did human morality evolve? And can humans become morally evolved? -/- In A Better Ape, Victor Kumar and Richmond Campbell draw on the latest research in the biological and social sciences to explain the key role that morality has played in human evolution. They explore the moral traits that (...) humans share with chimpanzees; how a more complex moral mind enabled Homo sapiens to arise and out-compete other human species; and the place of morality alongside historic revolutions in technology and social organization. Throughout the book, Kumar and Campbell argue that morality co-evolved with intelligence and complex sociality. Morality prevents societal collapse and enables complex knowledge. -/- After unearthing the ancient origins of human morality, Kumar and Campbell use evolutionary theory to deliver profound insights about how to advance moral progress and resist moral regress, such as reducing animal suffering on industrial farms; capitalizing on the recent revolution in gay rights to foster a nascent revolution in transgender rights; opposing intersectional inequality that impacts women and people of color in lower socioeconomic classes; and addressing major problems of global inequality, especially impending crises of injustice caused by anthropogenic climate change. Understanding how we evolved--and how we continue to evolve--can help us become a better ape. (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)