Exaggerated contraction of airway smooth muscle is the major cause of symptoms in asthma, but the mechanisms that prevent exaggerated contraction are incompletely understood. Here, we showed that integrin α 9β 1on airway smooth muscle localizes the polyamine catabolizing enzyme spermidine/spermine N 1-acetyltransferase in close proximity to the lipid kinase PIP5K1γ. As PIP5K1γ is the major source of PIP2 in airway smooth muscle and its activity is regulated by higher-order polyamines, this interaction inhibited IP3-dependent airway smooth muscle contraction. Mice lacking (...) integrin α 9β 1 in smooth muscle had increased airway responsiveness in vivo, and loss or inhibition of integrin α 9β 1 increased in vitro airway narrowing and airway smooth muscle contraction in murine and human airways. Contraction was enhanced in control airways by the higher-order polyamine spermine or by cell-permeable PIP2, but these interventions had no effect on airways lacking integrin α 9β 1 or treated with integrin α 9β 1-blocking antibodies. Enhancement of SSAT activity or knockdown of PIP5K1γ inhibited airway contraction, but only in the presence of functional integrin α 9β 1. Therefore, integrin α 9β 1 appears to serve as a brake on airway smooth muscle contraction by recruiting SSAT, which facilitates local catabolism of polyamines and thereby inhibits PIP5K1γ. Targeting key components of this pathway could thus lead to new treatment strategies for asthma. (shrink)

Jean‐Luc Marion has recently established himself as one of the most important and theologically fertile thinkers within the phenomenological tradition. With his study of ‘the gift’ and ‘the saturated phenomenon’, Marion presents a challenge to theology to rethink revelation in its surprising givenness, as exceeding the boundaries often set up in advance by metaphysics and a priori anthropological foundations. This paper examines Marion's mature thought, particularly within the perspective of Christology. The paper argues that Marion's phenomenological style of reflection, as (...) adapted to theology, is deeply contemplative and markedly Johannine in sensibility. As a strategy for theology, the phenomenological style gives to it important incentives and skills for reading off God's self‐revelation in Christ in its surprising and counter‐intuitive beauty. Marion's challenge/gift to theology is, however, in need of a balancing emphasis, one that appears too infrequently in his work: the ethical‐prophetic dimension of the Christ event. In view of keeping both the mystical and prophetic poles of theology closely linked, the paper argues that just as beauty is a key category for saturated phenomena, so too is the reality of suffering and evil. However, whereas beauty invites a humble receptivity to and contemplative enjoyment of the gift, the inscrutable reality of suffering and evil, which so often exceeds comprehension, touches off a critical and practical response. In broadening the study of saturated phenomena to include the refractory character of experience, especially that which threatens humanity, Marion's valuable contributions to theology require a complementary emphasis from those narrative‐practical Christologies that highlight the prophetic aspects of the tradition. (shrink)

Increasingly, national governments across the globe are prioritizing investments in neuroscience. Currently, seven active or in-development national-level brain research initiatives exist, spanning four continents. Engaging with the underlying values and ethical concerns that drive brain research across cultural and continental divides is critical to future research. Culture influences what kinds of science are supported and where science can be conducted through ethical frameworks and evaluations of risk. Neuroscientists and philosophers alike have found themselves together encountering perennial questions; these questions are (...) engaged by the field of neuroethics, related to the nature of understanding the self and identity, the existence and meaning of free will, defining the role of reason in human behavior, and more. With this Perspective article, we aim to prioritize and advance to the foreground a list of neuroethics questions for neuroscientists operating in the context of these international brain initiatives. (shrink)

In this paper I argue that Direct realism is less prone to internal incoherence as a theory of knowledge than alternative theories. The theory of Direct realism best grounds our capacity for cognition of the external world, whereas other epistemological theories claim to ground our capacity for cognition, but end in skepticism in the final analysis. I propose to show this contrast by bringing in different theories of a well-known Indirect realist, Bertrand Russell. Illustrating this point mainly through Russell makes (...) the approach purely historical in nature even when the paper includes a brief discussion of two theories in the current debate that support Direct realism. (shrink)

A volume in the International Library of the Philosophy of Education under the general editorship of R. S. Peters, which will both interest and repay close study by epistemologists and philosophers of language, as well as philosophers of education. The book concerns concept formation and the growth of knowledge, i.e., as the general editor of the series writes, "the genesis of knowledge and not just the logical properties of its outcome." The book is divided into two parts: in the first, (...) Hamlyn, employing a Piagetian framework and terminology, examines first the classical empiricist account of the genesis of knowledge, which, after Piaget, he strictures as "genesis without structure." This account fails to explain the existence of intersubjective agreement. Then Hamlyn goes on to examine the rival rationalist account, which he strictures as "structure without genesis." Here, the failure is that there is no good account of how knowledge even gets started. Finally, Hamlyn examines an account of the growth of knowledge to which he is more sympathetic; that of the French psychologist, Piaget: "structure with genesis." Hamlyn finds striking similarities between the Piagetian theory and that of Kant, but, in the end, this account has a fatal flaw as well. Indeed, according to Hamlyn, all three accounts really fail for the same basic cause, viz., their account of knowledge is too egocentric, and "they all start from the same starting point, the individual set against his environment." In the second part of the book, Hamlyn sets out his own view, the object of which is to correct the egocentric view of knowledge which undermines the traditional theories and even their more modern versions, in Chomsky as the representative of Rationalism, and Piaget, as the Kantian representative. Here Hamlyn argues that knowledge would be impossible without what Wittgenstein called "agreement in judgments" and then argues that this implies common reactions, attitudes, wants, and interests, in relation to the world. Finally, Hamlyn proceeds to apply this "social view" of knowledge and understanding to the acquisition of both in the case of the child. In the course of doing so, he relates the acquisition of knowledge and understanding in the child to the child’s acquisition of language. In the course of his discussion, Hamlyn has interesting things to say about a wide variety of topics such as "non-epistemic seeing" and the relations between knowledge and understanding. In addition he provides illuminatingly critical discussions of the main ideas of Piaget and Chomsky; and although most philosophers are persuaded that they should become familiar with the ideas of the latter, Hamlyn makes out a good case that philosophers ought to start to think about the work of the former as well. All of this is done in a pleasingly straightforward way, devoid of any tiresome literary conceits. (shrink)

The unknown nature of tomorrow’s research makes informed consent in biobank research a challenge. Whether the consent given by biobank participants is ‘broad’ or ‘narrow’, the ever present question remains the same: are new activities covered by the original consent? In this article, we focus on the meaning of, and the relation between, broad consent and re-consent in biobank research. We argue that broad consent should be understood as consenting to a framework—a framework which covers aims, core conditions for acceptable (...) use, governance and how these affect participants. Changes that alter the framework in a fundamental way call for re-consent. Three biobank cases of current international interest are used to debate when re-consent is an ethical necessity: whole-genome sequencing, data sharing and commercial utilization. These reflections give us a more nuanced view on what consent is for. We claim that the introduction of broad consents in biobank research has not represented a betrayal of individual participant interests, as some critics have asserted. Broad consents combined with the possible use of re-consent are in certain settings not inferior, but rather ethically superior to narrow consents. In population-based research biobanks, they allow for a reconciliation between individual interest and public matters in society at large. (shrink)

This paper explores one aspect of the political in the early Hegel, that of criminal action and its relationship to the concept of recognition in the System of Ethical Life. While it is clear that in this work Hegel thinks that criminal action plays an important role in the transformation of simple ethical communities, it is not clear that, for Hegel, the formal character of crime in the struggle for recognition is anything but negative. I attempt to show how this (...) role for crime leads Hegel to a legalistic conception of Right that has no solid connection with recognition as a social force. (shrink)

The first edition of ELL (1993, Ron Asher, Editor) was hailed as "the field's standard reference work for a generation". Now the all-new second edition matches ELL's comprehensiveness and high quality, expanded for a new generation, while being the first encyclopedia to really exploit the multimedia potential of linguistics. * The most authoritative, up-to-date, comprehensive, and international reference source in its field * An entirely new work, with new editors, new authors, new topics and newly commissioned articles with a handful (...) of classic articles * The first Encyclopedia to exploit the multimedia potential of linguistics through the online edition * Ground-breaking and International in scope and approach * Alphabetically arranged with extensive cross-referencing * Available in print and online, priced separately. The online version will include updates as subjects develop ELL2 includes: * c. 7,500,000 words * c. 11,000 pages * c. 3,000 articles * c. 1,500 figures: 130 halftones and 150 colour * Supplementary audio, video and text files online * c. 3,500 glossary definitions * c. 39,000 references * Extensive list of commonly used abbreviations * List of languages of the world (including information on no. of speakers, language family, etc.) * Approximately 700 biographical entries (now includes contemporary linguists) * 200 language maps in print and online Also available online via ScienceDirect - featuring extensive browsing, searching, and internal cross-referencing between articles in the work, plus dynamic linking to journal articles and abstract databases, making navigation flexible and easy. For more information, pricing options and availability visit www.info.sciencedirect.com. The first Encyclopedia to exploit the multimedia potential of linguistics Ground-breaking in scope - wider than any predecessor An invaluable resource for researchers, academics, students and professionals in the fields of: linguistics, anthropology, education, psychology, language acquisition, language pathology, cognitive science, sociology, the law, the media, medicine & computer science. The most authoritative, up-to-date, comprehensive, and international reference source in its field. (shrink)

OBJECTIVES: To compare the perceptions of physician executives and clinicians regarding ethical issues in Saudi Arabian hospitals and the attributes that might lead to the existence of these ethical issues. DESIGN: Self-completion questionnaire administered from February to July 1997. SETTING: Different health regions in the Kingdom of Saudi Arabia. PARTICIPANTS: Random sample of 457 physicians (317 clinicians and 140 physician executives) from several hospitals in various regions across the kingdom. RESULTS: There were statistically significant differences in the perceptions of physician (...) executives and clinicians regarding the existence of various ethical issues in their hospitals. The vast majority of physician executives did not perceive that seven of the eight issues addressed by the study were ethical concerns in their hospitals. However, the majority of the clinicians perceived that six of the same eight issues were ethical considerations in their hospitals. Statistically significant differences in the perceptions of physician executives and clinicians were observed in only three out of eight attributes that might possibly lead to the existence of ethical issues. The most significant attribute that was perceived to result in ethical issues was that of hospitals having a multinational staff. CONCLUSION: The study calls for the formulation of a code of ethics that will address specifically the physicians who work in the kingdom of Saudi Arabia. As a more immediate initiative, it is recommended that seminars and workshops be conducted to provide physicians with an opportunity to discuss the ethical dilemmas they face in their medical practice. (shrink)

Nonadherence to treatment continues to be one of psychiatry's greatest challenges. To improve adherence and thus improve the care of patients, clinicians and patients' family members sometimes resort to hiding medication in food or drink, a practice referred to as covert/ surreptitious medication. The practice of covert drug administration in food and beverages is well known in the treatment of psychiatrically ill world-wide but no prevalence rates exist. Covert medication may seem like a minor matter, but it touches on legal (...) and ethical issues of a patient's competence, autonomy, and insight. Medicating patients without their knowledge is not justifiable solely as a shortcut for institutions or families wishing to calm a troublesome patient and thus alleviate some of the burdens of care giving. The paramount principle is ensuring the well-being of a patient who lacks the competence to give informed consent. Ethically, covert/surreptitious administration can be seen as a breach of trust by the doctor or by family members who administer the drugs. Covert medication contravenes contemporary ethical practice. Legally, treatment without consent is permissible only where common law or statute provides such authority. The practice of covert administration of medication is not specifically covered in the mental health legislation in developing countries. Many of the current dilemmas in this area have come to public attention because of two important developments in medical ethics and the law - the increasing importance accorded to respect for autonomy and loss of the parens patriae jurisdiction of the courts [parens patriae means 'parent of the country'; it permitted a court to consent or refuse treatment on behalf of an 'incapacity', or alternatively to appoint a guardian with such powers]. (shrink)

The increasingly foreshortening of bioethics known as narrative and even literary bioethics is analyzed in article. This analysis is realized on the material of Rudyard Kipling’s story «The miracle of Purun Bhagat». Deconstruction in its ethical aspect comes out in this case as method of the overcoming of logocentrism and becomes radicalization of ethics. The talk is about consideration of bioethics not simply as the science of survival but as radical ethics of the salvation of life. The text of the (...) story is interpreted as pharrmacon, remedy, sure remedy for human consciousness, society and nature. The result of the analysis is the idea of the consideration of conservative bioethics as radical ethics of salvation and science about spiritual-moral essence of human. This essence is consciousness, which is always moral consciousness in contradiction to intellect deprivated of moral dimension and leading humankind on the way of catastrophic progress to transhumanistic, posthuman future. (shrink)