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)

For some of us, the defeasibility theory of knowledge remains the most plausible approach to the Gettier Problem. Epistemological fashion and faded memories notwithstanding, persuasive objections to the theory are very hard to find. The most impressive of those objections to the theory that have hitherto gone unanswered are examined and rejected here. These are objections put forward by Richard Feldman, Richard Foley, and John Turri. While these are all interesting, the objection recently put forward by Turri is, we think, (...) by far, the most serious threat to the theory that we have seen in a long time. A successful reply to it requires a surprising amount of care, as it turns out. If tenable, Turri's objection deals a devastating blow to the theory developed by Roderick Chisholm, Keith Lehrer, Peter Klein, Marshall Swain, Risto Hilpinen, John Pollock, and Paul Moser, among others. Under scrutiny, however, the threat proves illusory. It results from inattention to a crucial, but relatively subtle, aspect of.. (shrink)

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)

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)

Information can be public among a group. Whether or not information is public matters, for example, for accounts of interdependent rational choice, of communication, and of joint intention. A standard analysis of public information identifies it with (some variant of) common belief. The latter notion is stipulatively defined as an infinite conjunction: for p to be commonly believed is for it to believed by all members of a group, for all members to believe that all members believe it, and so (...) forth. This analysis is often presupposed without much argument in philosophy. Theoretical entrenchment or intuitions about cases might give some traction on the question, but give little insight about why the identification holds, if it does. The strategy of this paper is to characterize a practical-normative role for information being public, and show that the only things that play that role are (variants of) common belief as stipulatively characterized. In more detail: a functional role for “taking a proposition for granted” in non-isolated decision making is characterized. I then present some minimal conditions under which such an attitude is correctly held. The key assumption links this attitude to beliefs about what is public. From minimal a priori principles, we can argue that a proposition being public among a group entails common commitment to believe among that group. Later sections explore partial converses to this result, the factivity of publicity and publicity from the perspective of outsiders to the group, and objections to the aprioricity of the result deriving from a posteriori existential presuppositions. (shrink)

That space and time should be integrated into a single entity, spacetime, is the great insight of Einstein's special theory of relativity, and leads us to regard spacetime as a fundamental context in which to make sense of the world around us. But it is not the only one. Causality is equally important and at least as far as the special theory goes, it cannot be subsumed under a fundamentally geometrical form of explanation. In fact, the agent of propagation of (...) causal influence is electromagnetic radiation. In this examination, the authors find support for a rationalist approach to physics, never neglecting experimentation, but rejecting a simple empiricist or positivist view of science. (shrink)

The best philosophy of science during the last generation has been highly historical; and the best history of science, highly philosophical. No one has better exemplified this intimate relationship between history and philosophy than has Robert E. Butts in his work. Through out his numerous writings, science, its philosophy, and its history have been treated as a seamless web. The result has been a body of work that is sensitive in its conception, ambitious in its scope, and illuminat ing in (...) its execution. Not only has his work opened new paths of inquiry, but his enthusiasm for the discipline, his encouragement of others (particularly students and younger colleagues), and his tireless efforts to build an international community of scholars, have stimulated the growth of HPS throughout Europe and North America. Many of the essays in this volume reflect that influence. Our title, of course, is deliberately ambiguous. The essays herein are by colleagues and former students, all of us wishing to honour an intimate friend. Happy Birthday, Bob! IX INTRODUCTION The essays herein cover a variety of concerns: from Descartes to reduction, from Galileo to gambling, from Freud's psychoanalysis to Kant's thing-in-itself. But under this diversity there is an approach common to them all. Things are largely done with a concern for and a sensitivity to historical matters (including contemporary history, of course). (shrink)

The author of the acclaimed Gay Fiction Speaks brings us new interviews with twelve prominent gay writers who have emerged in the last decade. Hear Us Out demonstrates how in recent decades the canon of gay fiction has developed, diversified, and expanded its audience into the mainstream. Readers will recognize names like Michael Cunningham, whose Pulitzer Prize-winning novel The Hours inspired the hit movie; and others like Christopher Bram, Bernard Cooper, Stephen McCauley, and Matthew Stadler. These accounts explore the vicissitudes (...) of writing on gay male themes in fiction over the last thirty years--prejudices of the literary marketplace; social and political questions; the impact of AIDS; commonalities between gay male and lesbian fiction... and even some delectable bits of gossip. (shrink)

According to the thought experiment most commonly used to argue against reliabilism, Mr. Truetemp is given an unusual but reliable cognitive faculty. Since he is unaware of the existence of this faculty, its deliverances strike him as rather odd. Many think that Truetemp would not have justified beliefs. Since he satisfies the reliabilist conditions for justified belief, reliabilism appears to be mistaken. I argue that the Truetemp case is underdescribed and that this leads readers to make erroneous assumptions about Truetemp's (...) epistemic situation. After examining empirical studies of actual subjects who, like Truetemp, have received new perceptual faculties, I show that Truetemp must have been endowed with all of the reorganized neural circuitry and cognitive skills that subjects with new perceptual faculties normally acquire during a long and difficult process of adaptation and development. When readers realize how much more the designers of Truetemp's new faculty had to do than simply slip an artificial device under Truetemp's scalp, I find that they no longer think his beliefs would be unjustified. Because the thought experiment fails to support anti-reliabilist intuitions when further details of the case are made explicit, the Truetemp thought experiment does not constitute a clear and decisive counterexample to reliabilism. (shrink)

In this article, Lucas maintains the falseness of Mechanism - the attempt to explain minds as machines - by means of Incompleteness Theorem of Gödel. Gödel’s theorem shows that in any system consistent and adequate for simple arithmetic there are formulae which cannot be proved in the system but that human minds can recognize as true; Lucas points out in his turn that Gödel’s theorem applies to machines because a machine is the concrete instantiation of a formal system: therefore, for (...) every machine consistent and able of doing simple arithmetic, there is a formula that it can’t produce as true but that we can see to be true, and so human minds and machines have to be different. Lucas considers as well in this article some possible objections to his argument: for any Gödelian formula we could, for instance, construct a machine able to produce it or we could put the Gödelian formulae that we had proved as axioms of a further machine. However - as Lucas underlines - for every of such machines we could again formulate another Gödelian formula, the Gödelian formula of these machines, that they are not able to proof but that we can recognize as true. More general arguments, such as the possibility to escape Gödelian argument by suggesting that Gödel’s theorem applies to consistent systems while we could be inconsistent ones, are moreover refuted by Lucas by maintaining that our inconsistency corresponds to occasional malfunctioning of a machine and not to his normal inconsistency; indeed, a inconsistent machine is characterized by producing any statement, on the contrary human being are selective and not disposed to assert anything. (shrink)

Although there is a high degree of consensus in the existing literature regarding the importance of respect in mental health care, a realistic appraisal suggests that there is something of a disconnect between what is espoused in policy documents and what actually occurs in practice. As a result, this article seeks to explore and advance our understanding of the phenomenon of respect in mental health care and draws on real practice situations to illustrate this schism. To this end, the authors (...) present three case studies that focus on the following: “use of seclusion,” “respecting professional boundaries,” and “horizontal workplace violence.” The authors advance the, perhaps for some, provocative argument that it is relatively easy to write/speak about respect, while the reality of communicating respect to others is more difficult, challenging, and makes significant demands on the individual psychiatric/mental health nurse. (shrink)

In this 1970 introduction to philosophy Mr Taylor concentrates on two central topics - explanation and meaning. He takes the argument far enough to acquaint the reader first-hand with the methods and approach of analytical philosophy, and yet because of the scope of these two topics he is able to introduce many of the traditional philosophical problems in epistemology, metaphysics, ethics, aesthetics, and logic. By this approach he avoids the dangers both of superficiality and of undue technicality. Philosophers are concerned (...) to analyse and describe certain concepts and modes of argument, not to establish facts or conclusions of any sort that can be tested by formal demonstration or controlled observation; their findings cannot be conveniently categorized or graded into a comprehensive and progressive course of studies. Mr Taylor meets this difficulty with his extended discussions of specific topics and questions which have implications over the whole subject. (shrink)

This paper addresses the definition and the operational use of intuitions in philosophical methods in the form of a research study encompassing several regions of the globe, involving 282 philosophers from a wide array of academic backgrounds and areas of specialisation. The authors tested whether philosophers agree on the conceptual definition and the operational use of intuitions, and investigated whether specific demographic variables and philosophical specialisation influence how philosophers define and use intuitions. The results obtained point to a number of (...) significant findings, including that philosophers distinguish between intuitions used to formulate (discovery) and to test (justification) philosophical theory. The survey results suggest that strategies implemented to characterise philosophical intuition are not well motivated since, even though philosophers do not agree on a single account of intuition, they fail to capture a preferred usage of intuitions as aspects of discovery. The quantitative summary of survey findings informs the debate on this topic, and advances more defined routes for subsequent approaches to the study of intuitions. (shrink)

Arenhart_Krause_Uma-logica-da-indistinguibilidade.