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)

Summary In his book Serpentum et Draconum Historiae Libri Duo, the sixteenth-century Italian naturalist Ulisse Aldrovandi described and illustrated an alleged dragon that had supposedly been killed in 1572. The ?dragon? became famous and was the centrepiece of Aldrovandi's museum. The specimen, a long-necked, long-tailed, scale-covered biped with a thickened torso and a forked tongue, was unlike any currently known bipedal animal and is therefore suspicious. Even so, an explicit description of its true nature has not been published before now. (...) Here we examine Aldrovandi's description and illustration, compare these with extant animals, and conclude that the specimen was a taxidermic hoax. It was made by attaching the forelimbs of a common toad (Bufo bufo) to a European grass snake (Natrix natrix) the midsection of which had been replaced by that of a fish. Fake dragons abounded in the museums of Renaissance Europe, but only in a few cases has the mystery of their true nature been investigated. Aldrovandi's dragon can now be added to the list of such solved zoological mysteries. (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)

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.

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)

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.

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)

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)

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)

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.

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)

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)

This work, written from a neo-Pyrrhonian perspective, is an examination of contemporary theories of knowledge and justification. It takes ideas primarily found in Sextus Empiricus's Outlines of Pyrrhonism, restates them in a modern idiom, and then asks whether any contemporary theory of knowledge meets the challenges they raise. The first part, entitled "Gettier and the Problem of Knowledge," attempts to rescue our ordinary concept of knowledge from those philosophers who have assigned burdens to it that it cannot bear. Properly understood, (...) Fogelin shows that the concept of knowledge is unproblematic. The second part of this study, called "Agrippa and the Problem of Justification," examines Agrippa's contribution to Pyrrhonism, a systematic reduction of its procedures which came to be known as the "Five Modes Leading to the Suspension of Belief." These modes present a completely general procedure for refuting any claim a dogmatist might make. Though largely unnoticed, there is, according to Fogelin, an uncanny resemblance between problems posed by Agrippa's "Five Modes" and those that contemporary epistemologists address under the heading of a theory of justification. Fogelin examines the strongest contemporary theories of justification--in both foundationalist and anti-foundationalist forms. The conclusion is that recent philosophical writings on justification have made no significant progress in responding to the Pyrrhonian problems these writings have addressed. (shrink)

This chapter contains sections titled: Background Chisholm's Theory of Action Remaining Questions References.

Plantinga’s God and Other Minds, Reformed Epistemology articles, and Warrant Trilogy are all part of the same epistemological project. Although the project develops in phases focusing progressively on anti-theism, evidentialism, and internalism, the epistemology is consistently a Reidian particularism. It follows Roderick Chisholm’s famous particularist strategy for finding an epistemic criterion, uses principles of common sense from Thomas Reid as clear cases of beliefs satisfying that criterion, and applies that criterion to belief in God in order to show that (...) this belief is epistemically respectable. Understanding this will help to clarify Plantinga’s philosophical contributions to our understanding of religious belief. In my article I introduce Plantinga’s epistemological sources, explain the structure of his project, overview its development in these three phases, and correct some misunderstandings of Plantinga that arise from inattention to his Reidian particularism. I also show how Reidian particularism itself suggests an improvement to Plantinga’s epistemology which his critics often recommend: that we recognize that evidence for the existence of God, even if it is not necessary for theistic belief to be warranted, may yet be valuable. (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.

In his celebrated article on the contrary-to-fact conditional Roderick Chisholm makes the following astute observation.

A review‐article of Loren Baritz, City On a Hill, A History of Ideas and Myths in America, John Wiley and Sons C. Wright Mills, Sociology and Pragmatism, Paine‐Whitman Publishers Roderick M. Chisholm, Herbert Feigl, William K. Frankena, John Passmore, Manley Thompson, Philosophy, Prentice‐Hall Max Black, Philosophy in America, Cornell University Press.