Brock Macdonald1, Evi Vakiani2, Rhonda K Yantiss3, Jun Lee4, Robert S Brown Jr5, Samuel H Sigal61Division of Gastroenterology, Department of Medicine, University of California-San Francisco, San Francisco, CA, 2Department of Pathology, Memorial Sloan–Kettering Cancer Center, New York, NY, 3Department of Pathology and Laboratory Medicine, New York Weill Cornell Medical College, New York, NY, 4Division of Nephrology, Department of Medicine, Weill Cornell Medical College, New York, NY, 5Division of Gastroenterology, Department of Medicine, Columbia University College of Physicians and Surgeons, New York, (...) NY, 6Division of Gastroenterology and Hepatology, Department of Medicine, New York University, New York, NY, USA: The use of sirolimus as an alternative to calcineurin inhibitors for posttransplant immunosuppression is associated with a variety of inflammatory conditions. In this report, we describe the case of a 34-year-old man who developed abnormal liver tests 6 years after live-donor kidney transplantation and 5 years after initiation of sirolimus-based immunosuppression. Elevated aminotransferase levels persisted after withdrawal of potentially hepatotoxic medications, and serologic evaluation for viral hepatitis, autoimmune disease, and genetic disorders was unrevealing. Liver biopsy revealed prominent hepatocellular injury associated with a mixed inflammatory infiltrate and liver tests normalized within 2 weeks of discontinuation of sirolimus. In this report, we review previous reports of sirolimus hepatotoxicity and propose a unifying hypothesis for the various inflammatory conditions that have been attributed to sirolimus.Keywords: sirolimus, immunosuppression, transplant, inflammatory conditions, hepatotoxicity. (shrink)

1 Evidence-based policy requires researchers to provide the answers to ecological questions that are of interest to policy makers. To find out what those questions are in the UK, representatives from 28 organizations involved in policy, together with scientists from 10 academic institutions, were asked to generate a list of questions from their organizations. 2 During a 2-day workshop the initial list of 1003 questions generated from consulting at least 654 policy makers and academics was used as a basis for (...) generating a short list of 100 questions of significant policy relevance. Short-listing was decided on the basis of the preferences of the representatives from the policy-led organizations. 3 The areas covered included most major issues of environmental concern in the UK, including agriculture, marine fisheries, climate change, ecosystem function and land management. 4 The most striking outcome was the preference for general questions rather than narrow ones. The reason is that policy is driven by broad issues rather than specific ones. In contrast, scientists are frequently best equipped to answer specific questions. This means that it may be necessary to extract the underpinning specific question before researchers can proceed. 5 Synthesis and applications. Greater communication between policy makers and scientists is required in order to ensure that applied ecologists are dealing with issues in a way that can feed into policy. It is particularly important that applied ecologists emphasize the generic value of their work wherever possible. (shrink)

The covariant Klein-Gordon equation requires twice the boundary conditions of the Schrödinger equation and does not have an accepted single-particle interpretation. Instead of interpreting its solution as a probability wave determined by an initial boundary condition, this paper considers the possibility that the solutions are determined by both an initial and a final boundary condition. By constructing an invariant joint probability distribution from the size of the solution space, it is shown that the usual measurement probabilities can nearly be recovered (...) in the non-relativistic limit, provided that neither boundary constrains the energy to a precision near ℏ/t 0 (where t 0 is the time duration between the boundary conditions). Otherwise, deviations from standard quantum mechanics are predicted. (shrink)

There is a great deal of interest in the relation between the status of women and fertility—by humanists, academics and policy-makers concerned with bringing about fertility declines. The three aspects of women's status most frequently linked to fertility are their education, employment and type of husband-wife interaction. Research to date has not given us a clear and consistent explanation of these relationships and has not confirmed causality. The effects of these three factors on fertility vary considerably across national boundaries and (...) even within different sectors of the same society. Some of the assumptions held by both researchers and policymakers must be re-thought in the interests of more useful future research and of sounder policy. (shrink)

A time-symmetric formulation of nonrelativistic quantum mechanics is developed by applying two consecutive boundary conditions onto solutions of a time- symmetrized wave equation. From known probabilities in ordinary quantum mechanics, a time-symmetric parameter P0 is then derived that properly weights the likelihood of any complete sequence of measurement outcomes on a quantum system. The results appear to match standard quantum mechanics, but do so without requiring a time-asymmetric collapse of the wavefunction upon measurement, thereby realigning quantum mechanics with an important (...) fundamental symmetry. (shrink)

Provider claims to conscientious objection have generated a great deal of heated debate in recent years. However, the conflicts that arise when providers make claims to the "conscience" are only a subset of the more fundamental challenges that arise in health care practice when patients and providers come into conflict. In this piece, the author provides an account of patient-provider conflict from within the moral tradition of St. Thomas Aquinas. He argues that the practice of health care providers should be (...) understood as a form of practical reasoning and that this practical reasoning must necessarily incorporate both "moral" and "professional" commitments. In order to understand how the practical reasoning of provider should account for the needs and commitments of the patient and vice versa, he explores the account of dependence provided by Alasdair MacIntyre in his book Dependent Rational Animals. MacIntyre argues that St. Thomas’ account of practical reasoning should be extended and adapted to account for the embodied vulnerability of all humans. In light of this insight, providers must view patients not only as the subjects of their moral reflection but also as fellow humans upon whom the provider depends for feedback on the effectiveness and relevance of her practical reasoning. The author argues that this account precludes responsive providers from adopting either moral or professional conclusions on the appropriateness of interventions outside the individual circumstances that arise in particular situations. The adoption of this orientation toward patients will neither eradicate provider-patient conflict nor compel providers to perform interventions to which they object. But this account does require that providers attend meaningfully to the suffering of patients and seek feedback on whether their intervention has effectively addressed that suffering. (shrink)

Mind uploading speculation and debate often concludes that a procedure described as gradual in-place replacement preserves personal identity while a procedure described as destructive scan-and-copy produces some other identity in the target substrate such that personal identity is lost along with the biological brain. This paper demonstrates a chain of reasoning that establishes metaphysical equivalence between these two methods in terms of preserving personal identity.

Unique in all of literature, the Confessions combines frank and profound psychological insight into Augustine's formative years along with sophisticated and beguiling reflections on some of the most important issues in philosophy and theology. The essays contained in this volume, by some of the most distinguished recent and contemporary thinkers in the field, insightfully explore Augustinian themes not only with an eye to historical accuracy but also to gauge the philosophical acumen of Augustine's reflections.

This volume brings together flux essays by an eminent scholar on the origins, development, and import of Kant's philosophy, chiefly in its metaphysical aspects. Four of these were separately published between 1924 and 1926, but until now have been difficult to obtain, despite great demand. Their appearance here will be welcomed. The thesis emerging from these studies is that the critical philosophy originates in metaphysical probings concerning the nature and presuppositions of being, and issues in doctrines which, despite psychological, epistemological, (...) and ethical presentation, are intended to have definite ontological import. --L. K. B. (shrink)

Another beginners' text, emphasizing the problem of the relation between ordinary language and formal logic. From an exceedingly simplified introduction to semiotics, it moves through an analysis of conventions of ordinary English discourse to a presentation of an elementary non-standard symbolic propositional, class and modal logic. A matrix method is used throughout, facilitating the use of the same symbols for class and propositional relations. Chapters are included on probability, Mill's inductive methods, and logic and scientific method. Abundant, typically dull exercises (...) are provided.--L. K. B. (shrink)

A critique of modern empiricism, pressed ploddingly but capably from a renovated pragmatist standpoint. In Part I the author argues that a rigid distinction between the analytic and synthetic is presupposed by empiricism and yet leads to a conventionalism out of touch with experience. Part II attacks various attempts to base knowledge on of perceptual experience. The constructive position developed in Part III stresses the concept of experience as a plurality of contextual happenings, always involving formal and nonformal elements; the (...) formal structure is held to rest on conventions which should remain flexible, varying according to purposes. Though often clumsy, cluttered, and over-abstract, the discussion is informed and perceptive.--L. K. B. (shrink)

A characterization of the categories and theoretical orientation of Argentine "positivism" --in a broad but classical sense, amounting roughly to the identification of knowledge with the conclusions of experimental science--carried out through an historical study of the origins, development, and doctrines of indigenous philosophical and sociological theories. --L. K. B.

The wounds inflicted by Homer's warriors fascinate readers, since they are vividly described and often curious or even grotesque. Commentators have struggled to explain some of them since commentaries began: some of the explanations are more curious than the wounds. Not surprisingly, the commentaries have not usually been graced by a high standard of anatomical or, especially, physiological background knowledge, and are often misleading in these respects. When such knowledge is applied, some wounds which have appeared problematic become realistic, but (...) some which have been accepted as straightforward become problematic. (shrink)

A clear and well-written defense of the Christian theistic world-view, marked by a constructive and well-balanced philosophical orientation, with only slight hints, through most of the book, of the underlying religious fundamentalism. The stress on the fundamental importance of commitment is balanced by a recognition of its constitutive role in reasoning, and by an insistence on the need for the integration of the intellectual, the practical, and the religious. The author takes as his main field of evidence man's "power of (...) moral and rational self-transcendence," and builds upon an epistemological scheme involving a triad of methods of knowing--by acquaintance, by inference, and by moral self-acceptance. The book concludes with a frankly dogmatic summary of the author's evangelical convictions. --L. K. B. (shrink)

Background: Emergency exception to informed consent regulation was introduced to provide a venue to perform research on subjects in emergency situations before obtaining informed consent. For a study to proceed, institutional review boards need to determine if the regulations have been met.Aim: To determine IRB members’ experience reviewing research protocols using emergency exception to informed consent.Methods: This qualitative research used semistructured telephone interviews of 10 selected IRB members from around the US in the fall of 2003. IRB members were chosen (...) as little is known about their views of exception to consent, and part of their mandate is the protection of human subjects in research. Interview questions focused on the length of review process, ethical and legal considerations, training provided to IRB members on the regulations, and experience using community consultation and notification. Content analysis was performed on the transcripts of interviews. To ensure validity, data analysis was performed by individuals with varying backgrounds: three emergency physicians, an IRB member and a layperson.Results: Respondents noted that: emergency exception to informed consent studies require lengthy review; community consultation and notification regulations are vague and hard to implement; current regulations, if applied correctly, protect human subjects; legal counsel is an important aspect of reviewing exception to informed-consent protocols; and IRB members have had little or no formal training in these regulations, but are able to access materials needed to review such protocols.Conclusions: This preliminary study suggests that IRB members find emergency exception to informed consent studies take longer to review than other protocols, and that community consultation and community notification are the most difficult aspect of the regulations with which to comply but that they adequately protect human subjects. (shrink)

An attempt to clarify and establish systematically foundations for a "formal" science of axiology, relating it to the social sciences and humanities as mathematics is related to the natural sciences.--L. K. B.

A comparative methodological examination of neo-positivism and analytic philosophy, phenomenology, and existentialism. These are interpreted as springing from the cultural and existential crisis of our time, each responding to a genuine element of this crisis, and thus tending toward integration into a unified method by which modern thought can extricate itself from the crisis--a recognition of the logical analysis of language, tempered by phenomenology and an historical orientation, as the methodological basis of modern philosophy. Speculative metaphysics and cosmology are much (...) too lightly dismissed.--L. K. B. (shrink)

The report of a special commission engaged by the National Book Committee, Inc. to make an inquiry into the theory of censorship and the freedom to read. It presents 1. a philosophical, sociological, and legal analysis of the grounds and implications of censorship, 2. recommendations concerning the needed systematic empirical investigation into the effects of books, the formation of reading taste, etc., and 3. suggestions as to immediate action.--L. K. B.