The evolutionarily conserved Notch signaling pathway regulates a broad spectrum of cell fate decisions and differentiation processes during fetal and postnatal life. It is involved in embryonic organogenesis as well as in the maintenance of homeostasis of self‐renewing systems. In this article, we review the role of Notch signaling in the hematopoietic system with particular emphasis on lymphocyte development and highlight the similarities in Notch function between Drosophila and mammalian differentiation processes. Recent studies indicating that aberrant NOTCH signaling is frequently (...) linked to the induction of T leukemia in humans will also be discussed. BioEssays 27:1117–1128, 2005. © 2005 Wiley Periodicals, Inc. (shrink)

This volume is the first-ever collection of essays devoted to the Lurianic concept of tsimtsum. It contains eighteen studies in philosophy, theology, and intellectual history, which demonstrate the historical development of this notion and its evolving meaning: from the Hebrew Bible and the classical midrashic collections, through Kabbalah, Isaac Luria himself and his disciples, up to modernity (ranging from Spinoza, Böhme, Leibniz, Newton, Schelling, and Hegel to Scholem, Rosenzweig, Heidegger, Benjamin, Adorno, Horkheimer, Levinas, Jonas, Moltmann, and Derrida).

Over one hundred genes have been isolated from the human genome and shown to be causally related to specific human genetic diseases. Studies with gene‐specific probes have demonstrated that the mutations resulting in a particular phenotype are highly heterogeneous as a group, ranging from alterations in transcription or RNA processing in the nucleus, through to errors in mRNA translation in the cytoplasm. Even where the gene‐specific probe is not available, defects have been localized to chromosomal regions by family studies. Recently (...) developed methods for moving along the chromosome from a linked marker to the mutation are resulting in rapid advances in the understanding of many monogenic disorders. (shrink)

Researchers are required to seek consent from Indigenous communities prior to conducting research but there is inadequate information about how Indigenous people understand and become fully engaged with this consent process. Few studies evaluate the preference or understanding of the consent process for research with Indigenous populations. Lack of informed consent can impact on research findings. The Picture Talk Project was initiated with senior Aboriginal leaders of the Fitzroy Valley community situated in the far north of Western Australia. Aboriginal people (...) were interviewed about their understanding and experiences of research and consent processes. Transcripts were analysed using NVivo10 software with an integrated method of inductive and deductive coding and based in grounded theory. Local Aboriginal interpreters validated coding. Major themes were defined and supporting quotes sourced. Interviews with Aboriginal leaders were facilitated by a local Aboriginal Community Navigator who could interpret if necessary and provide cultural guidance. Participants were from all four major local language groups of the Fitzroy Valley; aged 31 years and above; and half were male. Themes emerging from these discussions included Research—finding knowledge; Being respectful of Aboriginal people, Working on country, and Being flexible with time; Working together with good communication; Reciprocity—two-way learning; and Reaching consent. The project revealed how much more there is to be learned about how research with remote Aboriginal communities should be conducted such that it is both culturally respectful and, importantly, meaningful for participants. We identify important elements in community consultation about research and seeking consent. (shrink)

Globalization has brought people around the world closer together in ways that have created greater uncertainty in their identity politics. This has sometimes strengthened local identities, despite attempts to create ‘universal’ forms of identity that impose one standard of appropriate conduct in the face of difference. Drawing from Dialogical Self Theory and from cosmopolitanism, we propose that adequately responding to the ethical and identity challenges presented by globalization requires having Global Consciousness: “a knowledge of both the interconnectedness and difference of (...) humankind, and a will to take moral actions in a reflexive manner on its behalf”. We argue that this approach can ground a distinctively normative psychology of globalization. We consider negative and positive aspects of the golden rule in equal and close relationships, and benevolence in unequal power relationships as behaviour guides for global consciousness, and theorize about institutional leadership that supports the provision of public goods. We offer empirical tests of this approach. (shrink)

The first comprehensive treatment of the relationship between biblical interpretation and Christian ethics.

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.

Book reviewed in this article: Mystical Bedlam: Madness, Anxiety, and Healing in Seventeenth Century England. By Michael MacDonald. Making It Crazy: An Ethnography of Psychiatric Clients in an American Community. By Sue E. Estroff. Mind, Mood, and Medicine: A Guide to the New Biopsychiatry. By Paul H. Wender, M.D. and Donald F. Klein, M.D.

ObjectivesDuring their lifetimes, a majority of musicians experience playing-related musculoskeletal disorders. PRMD prevalence is tied to instrument choice, yet most studies examine heterogeneous groups of musicians, leaving some high-risk groups such as oboists understudied. This paper aims to ascertain the prevalence and nature of PRMDs in oboists, determine relevant risk factors, and evaluate the efficacy of treatment methods in preventing and remedying injuries in oboe players.MethodsA 10-question online questionnaire on PRMDs and their treatments was completed by 223 oboists. PRMDs were (...) compared across gender, weekly playing hours, career level, age, and years of playing experience.ResultsOf all respondents, 74.9% reported having had at least one PRMD in their lifetime. A majority of these injuries were of moderate to extreme severity. Females reported significantly more severe injuries than males. No significant effects of career level, age, or years of playing experience were observed. We found significant non-linear relationships between weekly playing hours and PRMD prevalence and severity. Injuries were most commonly on the right side of the body, with the right thumb, wrist, hand, and forearm being most affected in frequency and severity. Of those injuries for which recovery information was provided, only 26.1% of injuries were “completely recovered.” The perceived effectiveness of a few treatments tended to be ranked more highly than others.ConclusionThe oboists in this study experienced high rates of PRMD, particularly in the right upper extremities. Females and those playing 7-9 and 16-18 h per week reported a significantly higher severity of injuries than other groups. (shrink)

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)

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)

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)

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)

Aim To ascertain the quantity and nature of gifts and items provided by the pharmaceutical industry in Australia to medical specialists and to consider whether these are appropriate in terms of justifiable ethical standards, empirical research and views expressed in the literature.

Of all my recollections connected with the H of C that of my having had the honour of being the first to make the claim of women to the suffrage a parliamentary question, is the most gratifying as I believe it to have been the most important public service that circumstances made it in my power to render. This is now a thing accomplished.….

So, on 22 July 1865, under the title ‘Philosophy and Punch’, did England's premier comic weekly greet the election of J. S. Mill as MP for Westminster. Mill held his seat for only one term, until the general election of 1868, when his Whig-Liberal colleague Robert Wellesley Grosvenor was re-elected, but Mill was replaced by the loser in 1865, the Conservative W. H. Smith, Jr., who, though he never went to sea, became the ruler of the Queen's navy. The reasons (...) for that reversal have engaged the attention of many, including Mill himself; I should like to introduce into the discussion material from an ignored source, the comic weeklies, which took a continued and close look at Mill's behaviour during his parliamentary years. While this evidence generally does not disconfirm earlier judgments—including my own— it does more than merely add to the induction. First, it shows how different political stances led journals to focus on different aspects of Mill's parliamentary career, and to adopt different rhetorical strategies in portraying him in picture and word. Second, it demonstrates how the hardening of party allegiances during the parliament of 1865–68, which accelerated in the preparatory campaigns for the general election of 1868, affected Mill adversely. Third, it suggests strongly that it was not his ‘crotchets’ or ‘whims’, especially women's suffrage and proportional representation, that damaged his chances for re-election, but his advocacy of causes unpopular with the majority of Liberals as well as with Conservatives. (shrink)

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)

By the death, last summer, of Jack Robson, the world of utilitarian studies and a wider world of scholarship on both sides of the Atlantic lost one of their most distinguished figures. It would not be appropriate here, even if it were possible now, to attempt a full and measured assessment of his work. Writing only a few months after the news of his death, while the sense of loss is still so sharp for all his many friends, two (...) things are possible. Something can and should be said to acknowledge and celebrate Robson's achievement as a scholar; and to this can be added some personal recollections of one whose human qualities were as outstanding as his scholarship. (shrink)