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)

"Permanent Things reminds us that some of the century's most imaginative minds - G. K. Chesterton, T. S. Eliot, C. S. Lewis, Dorothy Sayers, and Evelyn Waugh - were profoundly at odds with the secularist spirit of the age, seeing progressive enlightenment as ushering in, not a millennium of perfect freedom, but a Waste Land whose inhabitants - Waugh's "vile bodies," Eliot's "hollow men," Lewis's "men without chests" - can find refuge from their boredom and anomie only in the ceaseless (...) acquisition of things or in the consoling illusions of pseudo religions - "distracted from distraction by distraction," as Eliot memorably put it." "How does one explain the desolation of a world which, though richly endowed with material comforts, is mentally and spiritually impoverished? The essayists here are united, as were their subjects, by a need to try to answer this question. Modern man's poverty of spirit, visible alike in so much of his art and architecture, his literature and philosophy and political science, reflects his loss of any good reasons for living - his loss of the Permanent Things." "The Christian writers whose work is eloquently interpreted in this book repay our attention for at least two reasons. First is their ability to sharpen our awareness of what, by any previous civilized standards, must be called the abnormal condition of modern man. For all the writers treated in this book, it was never enough to simply capture the spiritual aridity of modern life. It was also necessary to speak of a moral order that may yet be restored by the expressive power and beauty of the written word."--BOOK JACKET.Title Summary field provided by Blackwell North America, Inc. All Rights Reserved. (shrink)

We agree with Caplan & Waters that there are problems with the single-resource theory of sentence comprehension. However, we challenge their dual-resource alternative on theoretical and empirical grounds and point to a more coherent solution that abandons the notion of working memory resources.

Peter Abelard (1079–1142 ce) was the most wide‐ranging philosopher of the twelfth century. He quickly established himself as a leading teacher of logic in and near Paris shortly after 1100. After his affair with Heloise, and his subsequent castration, Abelard became a monk, but he returned to teaching in the Paris schools until 1140, when his work was condemned by a Church Council at Sens. His logical writings were based around discussion of the “Old Logic”: Porphyry's Isagoge, aristotle'S Categories and (...) On Interpretation and boethius'S textbook on topical inference. They comprise a freestanding Dialectica (“Logic”; probably c.1116), a set of commentaries (known as the Logica [Ingredientibus], c. 1119) and a later (c. 1125) commentary on the Isagoge (Logica Nostrorum Petititoni Sociorum or Glossulae). In a work Abelard called his Theologia, issued in three main versions (between 1120 and c.1134), he attempted a logical analysis of trinitarian relations and explored the philosophical problems surrounding God's claims to omnipotence and omniscience. The Collationes (“Debates,” also known as “Dialogue between a Christian, a Philosopher and a Jew”; probably c.1130) present a rational investigation into the nature of the highest good, in which the Christian and the Philosopher (who seems to be modeled on a philosopher of pagan antiquity) are remarkably in agreement. The unfinished Scito teipsum (“Know thyself,” also known as the “Ethics”; c.1138) analyses moral action. (shrink)

It is argued that “human-centredness” will be an important characteristic of systems that learn tasks from human users, as the difficulties in inductive inference rule out learning without human assistance. The aim of “programming by example” is to create systems that learn how to perform tasks from their human users by being shown examples of what is to be done. Just as the user creates a learning environment for the system, so the system provides a teaching opportunity for the user, (...) and emphasis is placed as much on facilitating successful teaching as on incorporating techniques of machine learning. If systems can “learn” repetitive tasks, their users will have the power to decide for themselves which parts of their jobs should be automated, and teach the system how to do them — reducing their dependence on intermediaries such as system designers and programmers.This paper presents principles for programming by example derived from experience in creating four prototype learners: for technical drawing, text editing, office tasks, and robot assembly. A teaching metaphor (a) enables the user to demonstrate a task by performing it manually, (b) helps to explain the learner's limited capabilities in terms of a persona, and (c) allows users to attribute intentionality. Tasks are represented procedurally, and augmented with constraints. Suitable mechanisms for attention focusing are necessary in order to control inductive search. Hidden features of a task should be made explicit so that the learner need not embark on the huge search entailed by hypothesizing missing steps. (shrink)

Abstract:Vulnerability is an important criterion to assess the ethical justification of the inclusion of participants in research trials. Currently, vulnerability is often understood as an attribute inherent to a participant by nature of a diagnosed condition. Accordingly, a common ethical concern relates to the participant’s decisionmaking capacity and ability to provide free and informed consent. We propose an expanded view of vulnerability that moves beyond a focus on consent and the intrinsic attributes of participants. We offer specific suggestions for how (...) relational aspects and the dynamic features of vulnerability could be more fully captured in current discussions and research practices. (shrink)

BackgroundThe proper and ethical inclusion of PWLHIV and their young children in research is paramount to ensure valid evidence is generated to optimize treatment and care. Little empirical data exists to inform ethical considerations deemed most critical to these populations. Our study aimed to systematically review the empiric literature regarding ethical considerations for research participation of PWLHIV and their young children.MethodsWe conducted this systematic review in partnership with a medical librarian. A search strategy was designed and performed within the following (...) electronic databases: Ovid MEDLINE, Embase and CINAHL. We screened titles and abstracts using the following inclusion criteria: (1) a study population of PWLHIV or children under 5 years of age; and (2) collection of qualitative or quantitative data regarding ethics of research participation. Excluded were reviews, commentaries, policy statements, clinical care-related ethics concerns, abstracts, case studies, or studies unrelated to HIV research. Studies were appraised for quality, data were extracted, and studies were qualitatively analyzed using a principle-based ethical framework within the Belmont Report.ResultsOf the 7470 titles identified, 538 full-text articles were reviewed for eligibility and only three articles met full criteria for inclusion within this review. While we allowed for inclusion of studies involving young children born to mothers with HIV, only articles focused on PWLHIV were identified. Within the results of these studies, four themes emerged: (1) adequacy of informed consent; (2) consideration of paternal involvement; (3) balancing risks; and (4) access to research and treatment. A strength of this review is that it included perspectives of international research investigators, community leaders, and male partners. However, only two studies collected empiric data from PWLHIV regarding their experiences participating in researchConclusionResearchers and funding agencies should be aware of these considerations and appreciate the value of and critical need for formative research to ensure clinical trials involving PWLHIV promote ethical, well-informed research participation and, ultimately, improve care outcomes. More research is needed to create a comprehensive ethical framework for researchers when conducting studies with PWLHIV. (shrink)