While outcomes for children with T-cell acute lymphoblastic leukemia have improved dramatically, survival rates for patients with relapsed/refractory disease remain dismal. Prior studies indicate that glucocorticoid resistance is more common than resistance to other chemotherapies at relapse. In addition, failure to clear peripheral blasts during a prednisone prophase correlates with an elevated risk of relapse in newly diagnosed patients. Here we show that intrinsic GC resistance is present at diagnosis in early thymic precursor T-ALLs as well as in a subset (...) of non-ETP T-ALLs. GC-resistant non-ETP T-ALLs are characterized by strong induction of JAK/STAT signaling in response to interleukin-7 stimulation. Removing IL7 or inhibiting JAK/STAT signaling sensitizes these T-ALLs, and a subset of ETP T-ALLs, to GCs. The combination of the GC dexamethasone and the JAK1/2 inhibitor ruxolitinib altered the balance between pro- and anti-apoptotic factors in samples with IL7-dependent GC resistance, but not in samples with IL7-independent GC resistance. Together, these data suggest that the addition of ruxolitinib or other inhibitors of IL7 receptor/JAK/STAT signaling may enhance the efficacy of GCs in a biologically defined subset of T-ALL.Leukemia advance online publication, 30 May 2017; doi:10.1038/leu.2017.136. (shrink)

This article engages through an interdisciplinary approach to re-envision Tangintebu Theological College’s (TTC) model of theological education in the context of climate change in Kiribati. It utilises the anthropological theory of symbolic interactionism within missiological, cultural and, theological studies of climate change. It argues for the coconut tree as an appropriate cultural conceptual metaphorical idiom for translating and understanding Christian faith and shaping a theological pedagogy within the Kiribati context of climate change. The coconut image is an indigenous, holistic way (...) of knowing and learning informed by Kiribati cosmology embedded within people’s experiences and understanding of the coconut tree. Its life-centeredness has the potential to contextualise the theological curriculum and teaching methodology to assist in equipping theological students with climate change-sensitive approaches. The qualitative method was utilised to allow participants to reflect on their experiences of climate change in relation to the mission of the church. The data that informs this article was generated through unstructured interviews and focus group discussions with members of the Kiribati Uniting Church (KUC). The data was analysed using symbolic interactionism. The results suggest that the Kiribati people symbolically interact with God through their understanding of the coconut tree, which is conceived as the embodiment of God’s presence. It became clear that while this world view informs the faith of members of the KUC, the TTC curriculum has sidelined it, resulting in miseducation of pastors because this omission means they are not equipped to engage with the challenge of climate change. The participants argued that there is an urgent need to understand theological education and ministerial formation within the indigenous framework of Kiribati coconut imagination that is embedded in the promotion of justice and equitable society not only for human beings but for all of God’s creation through symbolic interaction with the presence of God in the coconut. (shrink)

Background If trials of therapeutic interventions are to serve society's interests, they must be of high methodological quality and must satisfy moral commitments to human subjects. The authors set out to develop a clinical - trials compendium in which standards for the ethical treatment of human subjects are integrated with standards for research methods. Methods The authors rank-ordered the world's nations and chose the 31 with >700 active trials as of 24 July 2008. Governmental and other authoritative entities of the (...) 31 countries were searched, and 1004 English-language documents containing ethical and/or methodological standards for clinical trials were identified. The authors extracted standards from 144 of those: 50 designated as ‘core’, 39 addressing trials of invasive procedures and a 5% sample of the remainder. As the integrating framework for the standards we developed a coherent taxonomy encompassing all elements of a trial's stages. Findings Review of the 144 documents yielded nearly 15 000 discrete standards. After duplicates were removed, 5903 substantive standards remained, distributed in the taxonomy as follows: initiation, 1401 standards, 8 divisions; design, 1869 standards, 16 divisions; conduct, 1473 standards, 8 divisions; analysing and reporting results, 997 standards, four divisions; and post-trial standards, 168 standards, 5 divisions. Conclusions The overwhelming number of source documents and standards uncovered in this study was not anticipated beforehand and confirms the extraordinary complexity of the clinical trials enterprise. This taxonomy of multinational ethical and methodological standards may help trialists and overseers improve the quality of clinical trials, particularly given the globalisation of clinical research. (shrink)

This book examines influential conceptions of sport and then analyses the interplay of challenging borderline cases with the standard definitions of sport. It is meant to inspire more thought and debate on just what sport is, how it relates to other activities and human endeavors, and what we can learn about ourselves by studying sport.

We surveyed selected physician members of the Society for Health and Human Values (SHHV) to study the benefits and problems of combining a medical career with a strong scholarly interest in the humanities. The 19 usable narrative responses characterized major benefits as experiential base and teaching opportunities. Barriers were numerous and fell under the general headings of: lack of time; lack of institutional rewards; lack of money for research and scholarship; lack of support from humanities peers; lack of suport from (...) medical colleagues; personal financial sacrifice; and lack of training. Some respondents offered creative solutions to these problems, including assertive negotiation of a job description, identification of helpful mentors, and various networking and administrative strategies. The survey results, while preliminary, suggest ways in which SHHV can assist clinicians who wish to develop a serious commitment to humanities study and teaching. (shrink)

J. S. Mill's distinction between higher and lower pleasures is often thought to conflict with his commitment to psychological and ethical hedonism: if the superiority of higher pleasures is quantitative, then the higher/lower distinction is superfluous and Mill contradicts himself; if the superiority of higher pleasures is not quantitative, then Mill's hedonism is compromised.

Probably no other psychologist has aroused such contrary reactions from the public and from the scientific community as Hans Eysenck. To the public, he was some kind of noble "IQ warrior" or that disgraceful "race and IQ guy." Playing with Fire is the first full-length biography of Eysenck's career to be published since his death in 1997.

Professor Roderick John Flower, Biochemical Pharmacology, William Harvey Research Institute, St Barts and the London School of Medicine Queen Mary University of London Charterhouse Square, London EC1M 6BQ, UK; [email protected] O'Neill, a molecular biologist in Frank Herbert's 1982 novel ‘The White Plague’,1 seeks retributive justice for the death of his wife in a terrorist bomb blast by infecting those he holds responsible with an engineered pathogen that kills only women. The eponymous plague soon spreads uncontrollably with predictable catastrophic global (...) consequences.When the definitive history of armed conflict is written, the chapter on biological weapons will make for a long and disagreeable read. Now, happily, disavowed by most nations under the 1972 Biological Weapons Convention, the presumption is that any future deployment would be at the hands of rogue states, criminal gangs or perhaps terrorist organisations, to whom they could appeal because of their apparent ease of preparation and dissemination coupled with their sinister reputation and potential for causing mass casualties.But Herbert's villain is different. He is a trained scientist possessing expert skills and with access to pathogens, reagents and cutting-edge technology. Such a person might appear outwardly to be part of the conventional academic establishment except that their motives impel them to act covertly outside the accepted ethical and legal boundaries of their profession. Such ‘outsiders’ evade detection because they act alone and can, through their privileged position, anticipate and thwart regulation or investigation. But is this frightening scenario more than just a plot for apocalyptic novels? Is it a credible threat?In reality, such occurrences seem to be rare. In a comprehensive analysis of 180 incidents involving the use of biological agents during the last century, for instance, Carus2 noted that none of the confirmed bioterrorist attacks by non-state actors …. (shrink)

A series of papers on different aspects of practical knowledge by Roderick Chisholm, Rudolf Haller, J. C. Nyiri, Eva Picardi, Joachim Schulte Roger Scruton, Barry Smith and Johan Wrede.

Taylor, R. A tribute.--Epistemology: Cornman, J. W. Chisholm on sensing and perceiving. Ross, J. F. Testimonial evidence. Lehrer, K. Reason and consistency. Keim, R. Epistemic values and epistemic viewpoints. Hanen, M. Confirmation, explanation, and acceptance. Canfield, J. V. "I know that I am in pain" is senseless. Steel, T. J. Knowledge and the self-presenting.--Metaphysics: Cartwright, R. Scattered objects. Duggan, T. J. Hume on causation. Arnaud, R. B. Brentanist relations. Johnson, M. L., Jr. Events as recurrables.--Ethics: Stevenson, J. T. On doxastic (...) responsibility. Feldman, F. World utilitarianism. Lamb, J. W. Some definitions for the theory of rules. Donnelly, J. Suicide: some epistemological considerations. (shrink)

Nelson, L. The impossibility of the "Theory of knowledge."--Moore, G. E. Four forms of skepticism.--Lehrer, K. Skepticism & conceptual change.--Quine, W. V. Epistemology naturalized.--Rozeboom, W. W. Why I know so much more than you do.--Price, H. H. Belief and evidence.--Lewis, C. I. The bases of empirical knowledge.--Malcolm, N. The verification argument.--Firth, R. The anatomy of certainty.--Chisholm, R. M. On the nature of empirical evidence.--Meinong, A. Toward an epistemological assessment of memory.--Brandt, R. The epistemological status of memory beliefs.--Malcolm, N. A definition (...) of factual memory.--Martin, C. B. and Deutscher, M. Remembering.--Ayer, A. J. Basic propositions.--Reichenbach, H. Are phenomenal reports absolutely certain?--Goodman, N. Sense and certainty.--Lewis, C. I. The given element in empirical knowledge.--Alston, W. Varieties of privileged access.--Schlick, M. The foundation of knowledge.--Russell, B. Epistemological premisses, basic propositions, and factual premisses.--Firth, R. Coherence, certainty, and epistemic priority.--Sellars, W. Empiricism and the philosophy of mind.--Quinton, A. The foundations of knowledge. (shrink)

Morality based upon categorical imperatives. On a supposed right to tell lies from benevolent motives, by I. Kant.--Utilitarian morality, by H. Sidgwick.--What makes right acts right? by Sir D. Ross.--Utilitarianism, universalisation, and our duty to be just, by J. Harrison.--Extreme and restricted utilitarianism, by J. J. C. Smart.--What if everyone did that? by C. Strang.--Toward a credible form of utilitarianism, by R. B. Brandt.

[TofC cont.] Social ideals: Justice, A utilitarian theory of justice / J.S. Mill, Egalitarianism with changed motivation / G. Cohen; Equality, Multidimensional equality / M. Walzer, Equality of capacity / A. Sen; Liberty, rights, property, and self-ownership, A defense of the primacy of liberty rights / L. Lomasky, Atomism and the primacy of rights / C. Taylor -- Social institutions: Education, Educating about familial values / W. Galston, For vouchers and parental choice / M. Friedman; Family, In defense of filial (...) obligations / C.H. Sommers; Punishment, A utilitarian theory of punishment / J. Bentham. In [this book, the editors] provide students [with] a wide variety of readings covering the problems of political and social philosophy. Such topics as political obligation, democracy, rights, and justice are represented, in addition to less widely discussed subjects as the family. Both common approaches and those which are less familiar are presented, as well as recent developments in the topic area. -Back cover. (shrink)

PERSON AND OBJECT by Roderick M. Chisholm. U.K.: Allen & Unwin; U.S.A.: Humanities Press, 1976. 230 pp. £7.25.

The aim of this series is to inform both professional philosophers and a larger readership (of social and natural scientists, methodologists, mathematicians, students, teachers, publishers, etc. ) about what is going on, who's who, and who does what in contemporary philosophy and logic. PROFILES is designed to present the research activity and the results of already outstanding personalities and schools and of newly emerging ones in the various fields of philosophy and logic. There are many Festschrift volumes dedicated to various (...) philosophers. There is the celebrated Library oj Living Phi/osophers edited by P. A. Schilpp whose format influenced the present enterprise. Still they can only cover very little of the contemporary philosophical scene. Faced with a tremendous expansion of philosophical information and with an almost frightening division of labor and increasing specialization we need systematic and regular ways of keeping track of wh at happens in the profession. PRO FILES is intended to perform such a function. Each volume is devoted to one or several philosophers whose views and results are presented and discussed. The profiled philosopher(s) will summarize and review his (their) own work in the main fields of signifi cant contribution. This work will be discussed and evaluated by invited contributors. Relevant historical and/or biographical data, an up-to date bibliography with short abstracts of the most important works and, whenever possible, references to significant reviews and discussions will also be included. (shrink)

This essay explains various significant errors, imprecisions, and omissions concerning libertarianism in Long 2013. The “right not to be aggressed against” is not, as such, the libertarian right because the ‘right to liberty’ must be that right (although not being aggressed against can charitably be interpreted as equivalent). There are non-libertarian rights, but they don’t override the right to liberty. Unsupported assumptions are inevitable because justifications are impossible. Rights should not be “defined” but, rather, morally and metaphysically theorised—with criticism permanently (...) invited. Moral and legal permissibility need to be clearly distinguished. The conceptions of “aggression” and “force” are normative and confused. It is possible to advocate the right to liberty on no grounds whatsoever and also to conjecture that liberty (deontologically) and welfare (consequentially) are systematically compatible in practice for theoretical and causal reasons. The rejection of positive rights is “privileging” and not “conceptual”. Libertarian property needs to be derived from an explicit, non-normative, theory of libertarian liberty. Long 2013’s overall account is “mysterious” and “one-sided”. (shrink)

A fundamental assumption of Alexius Meinong's 1904 Theory of Objects is the act-content-object analysis of psychological experiences. I suggest that Meinong's theory need not be based on this analysis, but that an adverbial theory might suffice. I then defend the adverbial alternative against an objection raised by Roderick Chisholm, and conclude by presenting an apparently more serious objection based on a paradox discovered by Romane Clark.