Abstractp53 is a multifunctional protein which plays a role in modulating gene transcription, policing cell cycle checkpoints, activating apoptosis, controlling DNA replication and repair, maintaining genomic stability and responding to genetic insults. Mutation of the p53 gene confers the single greatest known selective advantage favoring cancer formation. Point mutations result not only in the loss of tumor suppressor functions, but also in the gain of tumor promotion functions. These dual circumstances may be unique to p53 and, in part, could explain (...) the relatively powerful force behind this selection pressure. General mechanisms of gain of function by mutated p53 may include alteration in transcriptional modulation and newly acquired targets for transcriptional regulation and protein binding. Despite the direct significance of p53 mutations, loss of the remaining wild‐type allele is usually required for the formation of tumors in the natural setting. Novel applications of the basic scientific knowledge of p53 could lead to an improvement in cancer treatment, hopefully in the not so distant future. (shrink)

In light of a history of categorical exclusion, it is critical that pregnant people are included in research to help improve the knowledge base and interventions needed to address public health. Yet the volatile legal landscape around reproductive rights in the United States threatens to undue recent progress made toward the greater inclusion of pregnant people in research. We offer ethical and practical guidance for researchers, sponsors, and institutional review boards to take specific steps to minimize legal risks and ensure (...) the ethical conduct of research with pregnant people in an evolving legal environment. (shrink)

This honest, forthright, and beautifully-written book introduces readers to the human variations on medical topics spoken of in abstract in the daily news--euthanasia, assisted suicide, abortion, "extreme procedures", genetic testing, experimental surgeries--and to the people who must agonize over those decisions regarding themselves and their loved ones.

Four prominent views of the nature and methods of clinical ethics (especially in consultation forums) are reviewed; each is then submitted to a criticism intended to show both weaknesses and strengths. It is argued that clinical ethics needs to be responsive to the specific complexities of clinical situations. For this, the need for an expanded notion of practical reason within unique situations is emphasized, one whose aim is to facilitate decision-making on the part of those directly responsible for them and (...) consonant with their own respective moral frameworks and conceptions of what is most worthwhile. Keywords: Casuistry, clinical ethics, consultation, decision-making, dialogue, facilitator, practical reason, relationships CiteULike Connotea Del.icio.us What's this? (shrink)

This article reviews the historical and current controversies about the nature of clinical ethics consultation, as a way to focus on the place and responsibility of ethics consultants within the context of clinical conversation — interpreted as a form of dialogue. These matters are approached through a particularly compelling instance of the controversy that involves several major figures in the field. The analysis serves to highlight very significant questions of the nature and constraints of clinical situations, and the moral responsibility (...) and legal accountability that are especially important for clinical ethics consultants. (shrink)

This book uses Kant's idea of imperfect duty to extend the theory of the firm. Unlike perfect duty which is contractual or otherwise legally binding, imperfect duty consists of those commitments of choice that pursue some moral value, but that have practical limits to their pursuit. The author presents a broad view of the imperfect duties of management, defined as a nexus of all commitments to do good involving relations internal and external to the firm. This nexus consists of three (...) overlapping categories of (i) building a virtuous managerial community, (ii) pursuing reasoned managerial discourse, and (iii) diligent and reasoned pursuit of the body of routine managerial duties such as capital budgeting and internal controls. Specific applications of the nexus theory for stakeholder relations via fair negotiation, and for analysis of the effects on the managerial team of perquisite consumption are presented. This book has major implications for research in business ethics and allows critical insights into managerial decision making. (shrink)

Many of the errors that occur in children' subtraction are due to the use of incorrect strategies rather than to the incorrect recall of number facts. A production system is presented for performing written subtraction which is consistent with an earlier analysis of the nature of such a cognitive skill. Most of the incorrect strategies used by schoolchildren can be accounted for in a principled way by simple changes in the production system, such as the omission of individual rules or (...) the inclusion of rules appropriate to other arithmetical tasks. The production system model is evaluated against a corpus of over 1500 subtraction problems done by 10‐year olds and is shown to account for about two‐thirds of the (nonnumber fact) errors. It also provides an alternative, simpler interpretation of the subtraction errors analysed by Brown and Burton (1978). Some implications for teaching are discussed. (shrink)

Richard M Weaver, a thinker and writer celebrated for his unsparing diagnoses and realistic remedies for the ills of our age, is known largely through a few of his works that remain in print. This new collection of Weaver's shorter writings, assembled by Ted J Smith III, Weaver's leading biographer, presents many long-out-of-print and never-before-published works that give new range and depth to Weaver's sweeping thought. Included are eleven previously unpublished essays and speeches that were left in near-final form (...) at the time of Weaver's death in 1963. In all, there are some one hundred and twenty-six essays, speeches, book reviews, and editorials. (shrink)

Physicians have for some time been questioning the prevailing view of medicine as applied biology. It is urged that medicine needs to be reconceived so as to provide appropriate emphasis on the patient's experience and understanding of illness. After reviewing these arguments and the scientific paradigm underlying the received view in light of certain themes in medicine's history and of current thinking, Pellegrino's thesis is analyzed: medicine should be understood as an inherently moral enterprise, a form of praxis focused on (...) "the healing relationship". Understanding the illness experience and the professed healer's "compassion" supports Pellegrino's view, and suggests that the healing relationship is perhaps best conceived as a form of dialogue. Keywords: compassion, dialogue, healing relationship, illness experience, interpretation CiteULike Connotea Del.icio.us What's this? (shrink)

After a brief, personal reflection on Aron Gurwitsch’s life and his many influences on my career, I devote this lecture to some of the central themes of a phenomenology of medicine. Its core is the clinical encounter, which displays a certain structure I term the asymmetry of power (physician) and vulnerability (patient, family)—a complex contextual imbalance characterized by multiple points of view, hence points for reflective entrance. These are then interpreted phenomenologically in terms of epoché and reduction (practical distantiation), evidence, (...) reflection, and other related themes. I conclude with a suggestion about “the fundamental method” of phenomenology, free fantasy variation. (shrink)

Our intention here is to present the essential character of classical, sunnī kalām within a strictly formal perspective and to set out its basic aspects. It was conceived by the mutakallimīn as a rational, conceptual, and critical science and, although kalām differed in a number of basic concepts and constructs and in its analytic system, the topical organisation of the major compendia parallels that of metaphysics as understood in the contemporary Aristotelian tradition. The debates between kalām and falsafa need to (...) be examined within this context. Kalām, however, is theological in the strict sense of the term and it is as such that its problematic and its procedures are primarily to be understood. Thus seen, the object of kalām is to rationalise the cognitive content presented to Believers in the symbolic language of the koranic revelation. It has, then, four principal tasks, sc, to conceptualise, to order, to explain, and where possible to justify the primary doctrines of the community whose belief is held to be normative. Within this framework the differences that characterise the major schools as such and the various tendencies of individual masters within each school may readily be brought to light. On se propose ici de présenter, d'un point de vue strictement formel, la nature du kālam classique sunnite et d'identifier ses caractéristiques principales. II avait été conçu par les mutakallimin comme une science rationelle, conceptuelle et critique. L'organisation des matières dans ses traités reprend celle de la métaphysique dans la tradition aristotélicienne de l'époque, bien que le kalām s'en distingue par plusieurs de ses structures et concepts fondamentaux, ainsi que par son système analytique. C'est dans ce contexte qu'il faut considérer les debats qui s'instaurèrent entre kalām et falsafa. Le kalām, cependant, est d'ordre strictement théologique et c'est principalement dans ce cadre qu'il faut comprendre sa problématique et ses procédures. Le kalām a pour fonction de rationaliser le contenu cognitif offert aux croyants dans le langage symbolique de la révélation coranique. Il en résulte quatre tâches principales; il s'agit de conceptualiser, ordonner, expliquer et, dans le mesure du possible, justifier les doctrines principales reconnues par la communauté faisant référence en matière de croyance. Dans ce cadre, il sera possible de mettre en lumière les différences entre les principales écoles, ainsi que les tendances qui distinguent certains de leurs grands maîtres respectifs. (shrink)

Tested the 2-process theory of detection, search, and attention presented by the current authors in a series of experiments. The studies demonstrate the qualitative difference between 2 modes of information processing: automatic detection and controlled search; trace the course of the learning of automatic detection, of categories, and of automatic-attention responses; and show the dependence of automatic detection on attending responses and demonstrate how such responses interrupt controlled processing and interfere with the focusing of attention. The learning of categories is (...) shown to improve controlled search performance. A general framework for human information processing is proposed. The framework emphasizes the roles of automatic and controlled processing. The theory is compared to and contrasted with extant models of search and attention. (shrink)

In this volume, fourteen scholars, many of them contemporaries of Professor Frank, engage with his legacy with important and seminal works which take some of ...

In an overview of the essays in this project, a number of clinical ethics issues receive emphasis. (1) One cluster concerns the ethical concerns presented within the relationship between the providers (doctor, nurse, etc.) and patient (and family), as distinct from those associated with being a clinical ethics consultant invited into a situation to assist. (2) Distinct from these are ethical issues intrinsic to the ways in which clinical encounters are variously written about (from chart notes to published articles). (3) (...) Finally, there is a set of issues connected with the major characteristics of clinical encounters, in view of which it is imperative to be specifically attentive to the fine details and complex interactions among patient, doctor, family, and others, within a specific social context. Keeping these matters in mind helps to clarify the differences between consulting (talking and listening) and writing about consultations, as well as among the various kinds of writing about clinical encounters. (shrink)

The present study seeks to lay out the most basic elements of the ontology of classical Aš‘arite theology. In several cases this requires a careful examination of the traditional and the formal lexicography of certain key expressions. The topics primarily treated are: how they understood “Being/ existence” and “being/existent” and essential natures; the systematic exploitation of the equivocities of certain expressions within a general context in which other than words there are no universals proves to be elegant as well as (...) insightful; the basic categories of primary entities: independant beings and nonindependant beings, created and uncreated, the equivocity of “being/existent” as predicated of contingent entities on the one hand and of God and His attributes on the other, and certain problems that arise because of the rigid application of the system's underlying analytic principles. Nous essayons ici de presenter les éléments fondamentaux de l'ontologie de l'aš‘arisme classique. Pour quelques expressions, il a fallu examiner la lexicographie et ordinaire et technique pour bien comprendre leur emploi et leur signification. Les sujets examinés sont: le sens de “Etre/existence” et de “être/existant” et le concept de réalité essentielle; l'emploi nuancé des équivocités de quelques expressions dans un contexte où les seuls universaux sont des mots, emploi qui se révèle philosophiquement élégant; les catégories fondamentales des êtres: êtres indépendants et êtres non-indépendants, soit créés soit incréés, l'équivocité de “être/existant” dit des êtres contingents d'une part, de Dieu et ses attributs d'autre part, et enfin quelques difficultiés qui résultent de l'application rigide des principes analytiques du système. (shrink)

Despite the efforts of such notable thinkers as Sartre, Camus, and Ricoeur to affirm philosophically the being of evil, a systematic critique of the traditional metaphysical understanding of evil as privation of being has not yet been fully worked out. The task of this paper is to sketch out just such a critique and to suggest a more adequate philosophical reflection on the being of evil by turning to the thought of Heidegger. Part 1 examines Heidegger’s commentary on Aristotle’s remarks (...) on steresis. Aristotle is our teacher, Heidegger argues, in learning “to hold on to the wonder” of the steresis-dimension of Being (physis), and, thus, to hold on to the wonder that “lack,” “loss,” “absence” - is. Part II considers Heidegger’s recognition that the k-not at the very heart of our existence is yet much more complex. He turns to the fragments of Parmenides and Heraclitus to bring to light a dissembling-dimension of Being. (shrink)

The criterion of computational universality for an architecture should be replaced by the notion of compliancy, where a model built within an architecture is compliant to the extent that the model allows the architecture to determine the processing. The test should be that the architecture does easily – that is, enables a compliant model to do – what people do easily.

After expressing gratitude to each contributor, and briefly commenting on each, I probe several main themes of my work, addressing the question of the apparent difference between my earlier philosophical and later clinical writings. Central to both is the reflexivity of the human agent, and that each exhibits a form of practice regardless of the specific aims embedded in each. I then address the theme of narrative writing as my work has developed over the past several decades – at the (...) heart of which are questions of self and integrity. (shrink)

Ethics and the Clinical Encounter explores the moral dimensions of clinical medicine and the phenomenon of illness, to determine what ethics must be in order to be fully responsive to clinical encounters. Written in a lively and conversational style with minimal technical terminology, and enhanced by actual experience or real clinical situations, this volume lays out a clinical ethics methodology both in practical and theoretical terms. Here's what the experts had to say: Professor Zaner has provided us with a remarkably (...) lucid and trenchant discussion of the interface of philosophy and the field of medicine. He brings into play an extraordinary range of historial knowledge, extensive observations based on firsthand experience with medical practices, and an acute sense of philosophical argumentation. This is a work that will be an exemplary and indispensable text in the philosophy of medicine for years to come. -- Calvin Schrag... it is a highly original contribution usable in a number of fields.... It really has no competition.... The genius of Zaner's approach is to ground ethics from the 'bottom up' and to direct us to the concrete particulars of therapeutic encounters wherein lie moral and ethical matters... meaty, challenging, and ultimately rewarding.... -- Paul R. Dokecki Richard M. Zaner founded the Center for Clinical and Research Ethics at Vanderbilt University Medical Center. Having established Vanderbilt's first Hospital Ethics Committee (1985), he served as co-chair of VUMC's Ethics Committee since its inception in 1990. Zaner has published five original books, edited ten, and translated four more, and has published more than 100 sections of books and professional journals. (shrink)

This paper reviews objections to the proposal to allow parents of anencephalics to donate their infant's organs for transplantation and finds them unpersuasive. Instead, interpretations of ‘Baby Doe’ legislation, a ‘higher-brain’ functional conception of death, the idea of ‘viability’ in many abortion statutes, and the wishes of many patients, give strong support for the proposal for organ transplantation using anencephalics. Keywords: anencephalic, definition of death, transplantation CiteULike Connotea Del.icio.us What's this?

This essay focuses on questions central to Husserl’s essential methodology, specifically his notion of ‘free-fantasy variation,’ which he regarded as his ‘fundamental methodological insight.’ At the heart of this ‘vital element of phenomenology’ is what he often terms ‘as-if experience’ thanks to which anything whatever can be considered either for its own sake or as an example of something else. Further analysis explores the act of exemplification, the act of feigning and the shifts of attention and orientation that ground free-fantasy (...) variation. Exemplification and possibilizing are then examined in daily life to discern what makes the complex act of feigning at all possible. An examination of the phenomenon of upsets brings the core sense of possibilizing to light. A focus on the dramatic force intrinsic to these experiences, and the essential place of reflective awareness inherent to them, makes apparent how the rudimentary sense of self begins to emerge, and there follows an analysis of this self-referentiality of possibilizing. The analysis then concludes with a brief examination of Husserl’s so-called ‘zig-zag’ method of constitutive phenomenology. (shrink)