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)

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)

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; r.j.flower@qmul.ac.ukJohn 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)

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)

This landmark collection of essays by six renowned philosophers explores the implications of the contentious realism/antirealism debate for epistemology. The essays examine issues such as whether epistemology needs to be realist, the bearing of a realist conception of truth on epistemology, and realism and antirealism in terms of a pragmatist conception of epistemic justification. Richard Rorty's essay provides a critical commentary on the other five.

The following statement is a report of the Committee on Philosophy in Education of the American Philosophical Association and was approved by the Association's Board of Officers in September, 1959. The Committee was composed of the following: C. W. Hendel, Chairman, H. G. Alexander, R. M. Chisholm, Max Fisch, Lucius Garvin, Douglas Morgan, A. E. Murphy, Charner Perry, and R. G. Turnbull. Primary responsibility for the preparation of this report belonged to a subcommittee composed of Roderick M. Chisholm, Chairman, (...) H. G. Alexander, Lewis Hahn, Paul C. Hayner, and Charles W. Hendel. (shrink)

We define a concept of truthmaker function, and prove the functional completeness, w.r.t. truthmaker functions in this sense, of a set of four-valued functions corresponding to standard connectives of the system of relevance logic known as First-Degree Entailment or Belnap–Dunn logic.

This Is A New Release Of The Original 1905 Edition.

XLRI, in association with a few Tata Group companies, established the XLRI-JRD Tata Foundation in Business Ethics in 1991 to mark their long-standing commitment and contribution to business ethics in India. The foundation seeks to address this by publicly affirming the urgent need for ethics in business and the need to bring about a conducive culture in which it can thrive.

Robert Nozick sharply distinguished his vision of the free society from egalitarian liberals such as John Rawls. Less remarked upon is the distinction he drew between the free society governed by a strictly limited government and the society without any government at all. In this volume, the editors have brought together a selection of specially commissioned essays from key theorists actively involved in this debate.

“Towards a Theory of Taxation” is a proper theme for an Englishman to take when giving a paper in America. After all it was from the absence of such a theory that the United States derived its existence. The Colonists felt strongly that there should be no taxation without representation, and George III was unable to explain to them convincingly why they should contribute to the cost of their defense. Since that time, understanding has not advanced much. In Britain we (...) still maintain the fiction that taxes are a voluntary gift to the Crown, and taxing statutes are given the Royal Assent with the special formula, “La Reine remercie ses bons sujets, accepte leur benevolence, et ainsi le veult” instead of the simple “La Reine le veult,” and in the United States taxes have regularly been levied on residents of the District of Columbia who until recently had no representation in Congress, and by the State of New York on those who worked but did not reside in the State, and so did not have a vote. Taxes are regularly levied, in America as elsewhere, on those who have no say on whether they should be levied or how they should be spent. I am taxed by the Federal Government on my American earnings and by state governments on my American spending, but I should be hard put to it to make out that it was unjust. Florida is wondering whether to follow California in taxing multinational corporations on their world-wide earnings. (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)

This article investigates the claim that some truths are fundamentally or really true — and that other truths are not. Such a distinction can help us reconcile radically minimal metaphysical views with the verities of common sense. I develop an understanding of the distinction whereby Fundamentality is not itself a metaphysical distinction, but rather a device that must be presupposed to express metaphysical distinctions. Drawing on recent work by Rayo on anti-Quinean theories of ontological commitments, I formulate a rigourous theory (...) of the notion. In the final sections, I show how this package dovetails with ' interpretationist' theories of meaning to give sober content to thought that some things — perhaps sets, or gerrymandered mereological sums — can be 'postulated into existence'. (shrink)

This paper examines two puzzles of indeterminacy. The first puzzle concerns the hypothesis that there is a unified phenomenon of indeterminacy. How are we to reconcile this with the apparent diversity of reactions that indeterminacy prompts? The second puzzle focuses narrowly on borderline cases of vague predicates. How are we to account for the lack of theoretical consensus about what the proper reaction to borderline cases is? I suggest (building on work by Maudlin) that the characteristic feature of indeterminacy is (...) alethic normative silence, and use this to explain both plurality and lack of consensus. (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.

In the literature on supervaluationism, a central source of concern has been the acceptability, or otherwise, of its alleged logical revisionism. I attack the presupposition of this debate: arguing that when properly construed, there is no sense in which supervaluational consequence is revisionary. I provide new considerations supporting the claim that the supervaluational consequence should be characterized in a ‘global’ way. But pace Williamson (1994) and Keefe (2000), I argue that supervaluationism does not give rise to counterexamples to familiar inference-patterns (...) such as reductio and conditional proof. (shrink)

A change in sense of self is an outcome commonly associated with Buddhist meditation. However, the sense of self is construed in multiple ways, and which changes in self-related processing are expected, intended, or possible through meditation is not well understood. In a qualitative study of meditation-related challenges, six discrete changes in sense of self were reported by Buddhist meditators: change in narrative self, loss of sense of ownership, loss of sense of agency, change in sense of embodiment, change in (...) self-other or self-world boundaries, and loss of sense of basic self. Changes in sense of self could be transient or enduring, positive or distressing, enhancing or impairing. These changes were also given varied appraisals, ranging from insights associated with Buddhist doctrines to psychopathologies such as depersonalization. In this study of practitioners reporting meditation-related challenges, more global changes in sense of self were associated with higher levels of impairment. These results have implications for both Buddhist meditation as well as mindfulness-based interventions. (shrink)

We extend the theory of “Fine structure and iteration trees” to models having more than one Woodin cardinal.

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)

J. R. Lucas; XII—Or Else, Proceedings of the Aristotelian Society, Volume 69, Issue 1, 1 June 1969, Pages 207–222, https://doi.org/10.1093/aristotelian/69.1.207.