Although activated spinal cord glia contribute importantly to neuropathic pain, how nerve injury activates glia remains controversial. It has recently been proposed, on the basis of genetic approaches, that toll-like receptor 4 may be a key receptor for initiating microglial activation following L5 spinal nerve injury. The present studies extend this idea pharmacologically by showing that TLR4 is key for maintaining neuropathic pain following sciatic nerve chronic constriction injury. Established neuropathic pain was reversed by intrathecally delivered TLR4 receptor antagonists derived (...) from lipopolysaccharide. Additionally, -naltrexone, -naloxone, and -naloxone, which we show here to be TLR4 antagonists in vitro on both stably transfected HEK293-TLR4 and microglial cell lines, suppressed neuropathic pain with complete reversal upon chronic infusion. Immunohistochemical analyses of spinal cords following chronic infusion revealed suppression of CCI-induced microglial activation by -naloxone and -naloxone, paralleling reversal of neuropathic pain. Together, these CCI data support the conclusion that neuron-to-glia signaling through TLR4 is important not only for initiating neuropathic pain, as suggested previously, but also for maintaining established neuropathic pain. Furthermore, these studies suggest that the novel TLR4 antagonists -naloxone and -naloxone can each fully reverse established neuropathic pain upon multi-day administration. This finding with -naloxone is of potential clinical relevance. This is because -naloxone is an antagonist that is inactive at the -opioid selective receptors on neurons that produce analgesia. Thus, these data suggest that -opioid antagonists such as -naloxone may be useful clinically to suppress glial activation, yet -opioid agonists suppress pain. (shrink)

PURPOSE:To report the localization of a gene causing drusen and macular degeneration in a previously undescribed North American family. METHODS:Genetic mapping studies were performed using linkage analysis in a single family with drusen and atrophic macular degeneration. RESULTS:The clinical manifestations in this family ranged from fine macular drusen in asymptomatic middle-aged individuals to atrophic macular lesions in two children and two elderly patients. We mapped the gene to chromosome 6q14 between markers D6S2258 and D6S1644. CONCLUSIONS:In a family with autosomal dominant (...) drusen and atrophic macular degeneration, the gene maps to a 3.2-cM region on chromosome 6q14. This locus appears to be distinct from, but adjacent to, the loci for cone-rod dystrophy 7 (CORD7) and North Carolina macular dystrophy (MCDR1). Future identification of the gene responsible for the disease in this family will provide a better understanding of macular degeneration. (shrink)

Coronavirus disease 2019 can lead to respiratory failure. Some patients require extracorporeal membrane oxygenation support. During the current pandemic, health care resources in some cities have been overwhelmed, and doctors have faced complex decisions about resource allocation. We present a case in which a pediatric hospital caring for both children and adults seeks to establish guidelines for the use of extracorporeal membrane oxygenation if there are not enough resources to treat every patient. Experts in critical care, end-of-life care, bioethics, and (...) health policy discuss if age should guide rationing decisions. (shrink)

This clinical case report illustrates the potential dilemmas that can arise from knowledge gained through genetic analysis. These conflicts require careful ethical analysis of presumed duties to protect patient privacy and maintain confidentiality, the duty to warn a second party of a health risk, and the duty of veracity. While the questions raised by genetic testing of one individual for disease that reveals potentially important information about relatives, such as risk for Huntington chorea or breast cancer, have been discussed, the (...) continuing expansion in our capacity for sophisticated genetic analysis continues to present new and challenging situations. The resolution of this case and others like it requires close collaboration among the treatment team, geneticists, and clinical ethicists. (shrink)

© 2015, Springer-Verlag Berlin Heidelberg.Genetic studies have identified single nucleotide polymorphisms associated with the risk of prostate cancer. It remains unclear whether such genetic variants are associated with disease aggressiveness. The NCI-SPORE Genetics Working Group retrospectively collected clinicopathologic information and genotype data for 36 SNPs which at the time had been validated to be associated with PC risk from 25,674 cases with PC. Cases were grouped according to race, Gleason score and aggressiveness. Statistical analyses were used to compare the frequency (...) of the SNPs between different disease cohorts. After adjusting for multiple testing, only PC-risk SNP rs2735839 was significantly and inversely associated with aggressive and high-grade disease in European men. Similar associations with aggressive and high-grade disease were documented in African-American subjects. The G allele of rs2735839 was associated with disease aggressiveness even at low PSA levels in both European and African-American men. Our results provide further support that a PC-risk SNP rs2735839 near the KLK3 gene on chromosome 19q13 may be associated with aggressive and high-grade PC. Future prospectively designed, case-case GWAS are needed to identify additional SNPs associated with PC aggressiveness. (shrink)

The completeness of the modal logic S4 for all topological spaces as well as for the real line , the n-dimensional Euclidean space and the segment etc. was proved by McKinsey and Tarski in 1944. Several simplified proofs contain gaps. A new proof presented here combines the ideas published later by G. Mints and M. Aiello, J. van Benthem, G. Bezhanishvili with a further simplification. The proof strategy is to embed a finite rooted Kripke structure for S4 into a subspace (...) of the Cantor space which in turn encodes . This provides an open and continuous map from onto the topological space corresponding to . The completeness follows as S4 is complete with respect to the class of all finite rooted Kripke structures. (shrink)

Outstanding translations by leading contemporary scholars--many commissioned especially for this volume--are presented here in the first single edition to include the entire surviving corpus of works attributed to Plato in antiquity. In his introductory essay, John Cooper explains the presentation of these works, discusses questions concerning the chronology of their composition, comments on the dialogue form in which Plato wrote, and offers guidance on approaching the reading and study of Plato's works. Also included are concise introductions by Cooper and Hutchinson (...) to each translation, meticulous annotation designed to serve both scholar and general reader, and a comprehensive index. This handsome volume offers fine paper and a high-quality Smyth-sewn cloth binding in a sturdy, elegant edition. (shrink)

Theodor W. Adorno is best known for his contributions to aesthetics and social theory. Critics have always complained about the lack of a practical, political or ethical dimension to Adorno's philosophy. In this highly original contribution to the literature on Adorno, J. M. Bernstein offers the first attempt in any language to provide an account of the ethical theory latent in Adorno's writings. Bernstein relates Adorno's ethics to major trends in contemporary moral philosophy. He analyses the full range of Adorno's (...) major works, with a special focus on Dialectic of Enlightenment, Minima Moralia and Negative Dialectics. In developing his account Bernstein lays particular stress on Adorno's contention that the event of Auschwitz demands a new categorical imperative. This book will be widely acknowledged as the standard work on Adorno's ethics and as such will interest professionals and students of philosophy, political theory, sociology, history of ideas, art history and music. (shrink)

CONSCIOUSNESS AND THE BRAIN SELF-REGULATION PARADOX The relationship of consciousness to biology has intrigued mankind thoroughout recorded history. However, little progress has been made not only in understanding these issues but also in raising fundamental questions central to the problem. As Davidson and Davidson note in their introduction, William James suggested, almost a century ago in his Principles of Psychology, that the brain was the organ of mind and be havior. James went so far as to suggest that the remainder (...) of the Principles was but a "footnote" to this central thesis. This volume brings together diverse biobehavioral scientists who are addressing the various aspects of the mindlbrainlbodylbehavior issue. Although some of the authors have previously published together in other volumes, by and large the particular combination of authors and topics selected by the editors makes this volume unique and timely. Unlike the Consciousness and Self-Regulation series (Schwartz & Shapiro, 1976, 1978), also published by Plenum, this volume is devoted entirely to a psychobiological approach to consciousness. Although readers will differ in their interest in specific chapters, the well-rounded investigator who is concerned with the psychobiology of consciousness will want to become intimately acquainted with all the views presented in this volume. As noted by the individual contributors, the topic of this volume stimulates fundamental questions which, on the surface, may appear trivial, yet, on further reflection, turn out to have deep significance. (shrink)

The idea of human cruelty to animals so consumes novelist Elizabeth Costello in her later years that she can no longer look another person in the eye: humans, especially meat-eating ones, seem to her to be conspirators in a crime of stupefying magnitude taking place on farms and in slaughterhouses, factories, and laboratories across the world. Costello's son, a physics professor, admires her literary achievements, but dreads his mother’s lecturing on animal rights at the college where he teaches. His colleagues (...) resist her argument that human reason is overrated and that the inability to reason does not diminish the value of life; his wife denounces his mother’s vegetarianism as a form of moral superiority. At the dinner that follows her first lecture, the guests confront Costello with a range of sympathetic and skeptical reactions to issues of animal rights, touching on broad philosophical, anthropological, and religious perspectives. Painfully for her son, Elizabeth Costello seems offensive and flaky, but—dare he admit it?—strangely on target. In this landmark book, Nobel Prize–winning writer J. M. Coetzee uses fiction to present a powerfully moving discussion of animal rights in all their complexity. He draws us into Elizabeth Costello’s own sense of mortality, her compassion for animals, and her alienation from humans, even from her own family. In his fable, presented as a Tanner Lecture sponsored by the University Center for Human Values at Princeton University, Coetzee immerses us in a drama reflecting the real-life situation at hand: a writer delivering a lecture on an emotionally charged issue at a prestigious university. Literature, philosophy, performance, and deep human conviction—Coetzee brings all these elements into play. As in the story of Elizabeth Costello, the Tanner Lecture is followed by responses treating the reader to a variety of perspectives, delivered by leading thinkers in different fields. Coetzee’s text is accompanied by an introduction by political philosopher Amy Gutmann and responsive essays by religion scholar Wendy Doniger, primatologist Barbara Smuts, literary theorist Marjorie Garber, and moral philosopher Peter Singer, author of Animal Liberation. Together the lecture-fable and the essays explore the palpable social consequences of uncompromising moral conflict and confrontation. (shrink)

The number of discriminable colours is often assumed to be of the order of several million but the extent of detectable chromatic diversity present in individual natural scenes is an open question. Here, the aim was to estimate the number of discriminable colours seen in natural scenes. Hyperspectral data were obtained from a set of natural scenes over the range 400 - 720 nm at 10 nm intervals (Nascimento et al, 2002 Journal of the Optical Society of America A 19 (...) 1484 - 1490) and the representation of each scene in CIELAB space computed for all pixels of the image. The number of discriminable colours was estimated by counting the number of unit volumes in the three-dimensional volume defined by the scene when represented in CIELAB space. We found that the number of discriminable colours estimated in a scene could vary by an order of magnitude from scene to scene, but rarely exceeded 105, indicating a limited chromatic diversity. (shrink)

In this unflinching look at the experience of suffering and one of its greatest manifestations—torture—J.M. Bernstein critiques the repressions of traditional moral theory, showing that our morals are not immutable ideals but fragile constructions that depend on our experience of suffering itself. Morals, Bernstein argues, not only guide our conduct but also express the depth of mutual dependence that we share as vulnerable and injurable individuals. Beginning with the attempts to abolish torture in the eighteenth century, and then sensitively examining (...) what is suffered in torture and related transgressions, such as rape, Bernstein elaborates a powerful new conception of moral injury. Crucially, he shows, moral injury always involves an injury to the status of an individual as a person—it is a violent assault against his or her dignity. Elaborating on this critical element of moral injury, he demonstrates that the mutual recognitions of trust form the invisible substance of our moral lives, that dignity is a fragile social possession, and that the perspective of ourselves as potential victims is an ineliminable feature of everyday moral experience. (shrink)

In this 1974 book a practising scientist and gifted expositor sets forth an exciting point of view on the nature of science and how it works.

Theodor Adorno's Aesthetic Theory offers one of the most powerful and comprehensive critiques of art and of the discipline of aesthetics ever written. The work offers a deeply critical engagement with the history and philosophy of aesthetics and with the traditions of European art through the middle of the 20th century. It is coupled with ambitious claims about what aesthetic theory ought to be. But the cultural horizon of Adorno's Aesthetic Theory was the world of high modernism, and much has (...) happened since then both in theory and in practice. Adorno's powerful vision of aesthetics calls for reconsideration in this light. Must his work be defended, updated, resisted, or simply left behind? This volume gathers new essays by leading philosophers, critics, and theorists writing in the wake of Adorno in order to address these questions. They hold in common a deep respect for the power of Adorno's aesthetic critique and a concern for the future of aesthetic theory in response to recent developments in aesthetics and its contexts. (shrink)

Book reviewed in this article: Just War Tradition and the Restraint of War: A Moral and Historical Inquiry. By James Turner Johnson.

Jurgen Habermas' construction of a critical social theory of society grounded in communicative reason is one of the very few real philosophical inventions of recent times that demands and repays extended engagement. In this elaborate and sympathetic study which places Habermas' project in the context of critical theory as a whole past and future, J. M. Bernstein argues that despite its undoubted achievements, it contributes to the very problems of ethical dislocation and meaninglessness it aims to diagnose and remedy. Bernstein (...) further argues that the precise character of the failures of Habermas' program demonstrate the necessity for a return to the first generation critical theory of Adorno. Reading across nearly the whole range of Habermas' corpus, Recovering Ethical Life traces the development of the theory of communicative reason from its inception in Knowledge and Human Interests through its elaboration in The Theory of Communicative Action and into its defense against postmodernism in The Philosophical Discourse of Modernity . In separate chapters Habermas' readings of Freud, Durkheim amd Mead, Adorno and Foucault, Castoriadis and Taylor are critically examined. The focus of Bernstein's analyses, however, is always problem centered and thematic rather than textual psychoanalytic theory as an account of self knowledge, the competing claims of ethical identity and moral reason, the place of judgment in practical reason, and the debate between philosophies of language based communities versus those oriented towards world-disclosure. Critical theory is unique among current philosophies in engaging with the problems of social injustice and nihilism by siding with an abstract moral reason that forfeits the processes of intersubjective recognition it intended to salvage. Even in the fine grain of Habermas' account of performative contradictions and the theory of discourses of application, Bernstein perceives a squandering of the resources of an ethical life in need of transfiguration. (shrink)

Aesthetic alienation may be described as the paradoxical relationship whereby art and truth have come to be divorced from one another while nonetheless remaining entwined. J. M. Bernstein not only finds the separation of art and truth problematic, but also contends that we continue to experience art as sensuous and particular, thus complicating and challenging the cultural self-understanding of modernity. Bernstein focuses on the work of four key philosophers—Kant, Heidegger, Derrida, and Adorno—and provides powerful new interpretations of their views. Bernstein (...) shows how each of the three post-Kantian aesthetics to construct a philosophical language that can criticize and displace the categorical assumption of modernity. He also examines in detail their responses to questions concerning the relations among art, philosophy, and politics in modern societies. (shrink)

The problem of 'no fault' compensation for patients who suffer adverse effects as a result of their participation in clinical trials is discussed in the light of the guidelines issued by the Association of the British Pharmaceutical Industry (ABPI) and our recent experiences in reviewing protocols submitted to the local ethics of surgical research sub-committee. We have found a variety of qualifications being applied by pharmaceutical firms which are not in the spirit of the guidelines, let alone the interests of (...) the patient, and we suggest a means whereby the patients can be assured of fair treatment in the event of 'no fault' injury. (shrink)