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)

Although the University of Leeds has attained something of a reputation for the quality of its scholarship in the history of science, few historians are aware of the impressive collection of early scientific and medical books and manuscripts to be found in the University libraries. In order to make the library resources more widely known, we embarked on a systematic survey of the contents of the main historical collections. We wanted not only to give a general impression of the particular (...) strengths and distinctive features of each collection, but also to mention the interesting or rare copies of individual works to be found in them. We have, therefore, examined every book related to the history of science and medicine in the relevant collections, and in doing so we have uncovered a number of important items. For example, we have identified a book which was once in Newton's library, and a previously unrecorded copy of Joseph Black's chemical lectures. More generally, we had not suspected the true size and range of the Chaston Chapman Collection, which makes it a valuable resource for the history of alchemy and early chemistry; nor were we initially aware of the strength of the Historical Collection of the Medical and Dental Library. The wealth of the legacies to the Brotherton and Special Collections also impressed us. (shrink)

Safe stair negotiation is an everyday task that children with developmental coordination disorder are commonly thought to struggle with. Yet, there is currently a paucity of research supporting these claims. We investigated the visuomotor control strategies underpinning stair negotiation in children with and without DCD by measuring kinematics, gaze behavior and state anxiety as they ascended and descended a staircase. A questionnaire was administered to determine parents' confidence in their child's ability to safely navigate stairs and their child's fall history. (...) Kinematics were measured using three-dimensional motion capture, whilst gaze was measured using mobile eye-tracking equipment. The parents of DCD children reported significantly lower confidence in their child's ability to maintain balance on the stairs and significantly more stair-related falls in the previous year compared to the parents of typically developing children. During both stair ascent and stair descent, the children with DCD took longer to ascend/descend the staircase and displayed greater handrail use, reflecting a more cautious stair negotiation strategy. No differences were observed between groups in their margin of stability, but the DCD children exhibited significantly greater variability in their foot-clearances over the step edge, which may increase the risk of a fall. For stair descent only, the DCD children reported significantly higher levels of state anxiety than the TD children and looked significantly further along the staircase during the initial entry phase, suggesting an anxiety-related response that may bias gaze toward the planning of future stepping actions over the accurate execution of an ongoing step. Taken together, our findings provide the first quantifiable evidence that safe stair negotiation is a significant challenge for children with DCD, and that this challenge is reflected by marked differences in their visuomotor control strategies and state anxiety levels. Whilst it is currently unclear whether these differences are contributing to the frequency of stair-related falls in children with DCD, our findings pave the way for future research to answer these important questions. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:"The Fittest Man in the Kingdom":Thomas Reid and the Glasgow Chair of Moral PhilosophyPaul Wood (bio)Paul Wood Paul Wood is at the Department of History, University of Victoria, PO Box 3045, MS 7381, Victoria BC V8W 3P4 Canada. email: [email protected] August 1996Revised January 1997Notes. An earlier version of this paper was delivered at a plenary session of the 23rd International Hume Conference held at the University (...) of Nottingham. For comments and/or references, the author wishes to thank Roger Emerson, Carol Gibson-Wood, Knud Haakonssen, Ian Simpson Ross, Stephen Snobelen, M. A. Stewart, and the anonymous Hume Studies referees. For permission to cite and quote from manuscripts, he is grateful to the Keeper of the Manuscripts of Scotland as well as to the Librarians of Aberdeen University Library, Edinburgh University Library, Glasgow University Archives and Business Records Centre, Glasgow University Library (Department of Special Collections), the Mitchell Library Glasgow, and Dr. Williams' Library.1. Although little information survives regarding Law's teaching, we do know that he discussed Pufendorf in his classes; see Christine Mary King [Shepherd], "Philosophy and Science in the Arts Curriculum of the Scottish Universities in the Seventeenth Century," (Unpublished Ph.D. Dissertation, University of Edinburgh, 1974), 177. Carmichael's edition of Pufendorf first appeared in Glasgow in 1718, and a second edition was published in Edinburgh in 1724 while Hume was still a student there.2. The surviving correspondence between the two men from this period is to be found in The Letters of David Hume, ed. J.Y.T. Greig, 2 vols. (Oxford: Clarendon Press, 1932), I 32-35; 36-40; 45-48 (hereafter abbreviated as HL).3. The first detailed discussion of the 1745 election appeared in the introduction to David Hume, A Letter from a Gentleman to His Friend in Edinburgh, edited by Ernest C. Mossner and John V. Price (Edinburgh: Edinburgh University Press, 1967). This account has recently been challenged in Roger L. Emerson, "The 'Affair' at Edinburgh and the 'Project' at Glasgow: The Politics of Hume's Attempts to become a Professor," in Hume and Hume's Connexions, edited by M. A. Stewart and John P. Wright (Edinburgh: Edinburgh University Press, 1994), 1-22; and M. A. Stewart, The Kirk and the Infidel (Lancaster: Lancaster University Publications Office, 1995). For historically sensitive contextual analysis of Hume's philosophical relations with Hutcheson, see inter alia James Moore, "Hume and Hutcheson," in Stewart and Wright, 23-57, and M. A. Stewart, Warmth in the Cause of Virtue (Edinburgh: Edinburgh University Press, forthcoming).4. In January 1752, "Mr. Smith read an Account of some of Mr. David Hume's Essays on Commerce" to the Society, and Hume was elected a member in 1753; see Notices and Documents Illustrative of the Literary History of Glasgow, During the Greater Part of Last Century, edited by W. J. Duncan (Glasgow: T. D. Morison, 1886), 132-133. Hume's failed candidacy is discussed in Emerson, "The 'Affair' at Edinburgh," 14-16, and Ian Simpson Ross, The Life of Adam Smith (Oxford: Clarendon Press, 1995), 112-113. Smith's Glasgow colleague from 1751 to 1755, William Cullen, was also sympathetic to Hume's philosophy, as was John Millar, who was elected Professor of Law in 1761. On Cullen and Hume see J.R.R. Christie, "Ether and the Science of Chemistry: 1740-1790," in Conceptions of Ether: Studies in the History of Ether Theories 1740-1900, edited by G. N. Cantor and M.J.S. Hodge (Cambridge: Cambridge University Press, 1981), 90-96.5. David Hume to William Strahan, 26 October 1775, HL II 301.6. See, for example, The Works of Thomas Reid, D.D., edited by Sir William Hamilton, 4th ed. (Edinburgh: Maclachlan and Stewart, 1854), 30n; James McCosh, The Scottish Philosophy, Biographical, Expository, Critical, from Hutcheson to Hamilton (London: Macmillan, 1875), 36; James Veitch, "Philosophy in the Scottish Universities," Mind 2 (1877): 207-234 (209).7. John Rae, Life of Adam Smith (London and New York: Macmillan, 1895); William Robert Scott, Francis Hutcheson: His Life, Teaching and Position in the History of Philosophy (Cambridge: Cambridge University Press, 1900); idem., Adam Smith as Student and Professor (Glasgow: Jackson... (shrink)

In lieu of an abstract, here is a brief excerpt of the content:"The Fittest Man in the Kingdom":Thomas Reid and the Glasgow Chair of Moral PhilosophyPaul Wood (bio)Paul Wood Paul Wood is at the Department of History, University of Victoria, PO Box 3045, MS 7381, Victoria BC V8W 3P4 Canada. email: [email protected] August 1996Revised January 1997Notes. An earlier version of this paper was delivered at a plenary session of the 23rd International Hume Conference held at the University (...) of Nottingham. For comments and/or references, the author wishes to thank Roger Emerson, Carol Gibson-Wood, Knud Haakonssen, Ian Simpson Ross, Stephen Snobelen, M. A. Stewart, and the anonymous Hume Studies referees. For permission to cite and quote from manuscripts, he is grateful to the Keeper of the Manuscripts of Scotland as well as to the Librarians of Aberdeen University Library, Edinburgh University Library, Glasgow University Archives and Business Records Centre, Glasgow University Library (Department of Special Collections), the Mitchell Library Glasgow, and Dr. Williams' Library.1. Although little information survives regarding Law's teaching, we do know that he discussed Pufendorf in his classes; see Christine Mary King [Shepherd], "Philosophy and Science in the Arts Curriculum of the Scottish Universities in the Seventeenth Century," (Unpublished Ph.D. Dissertation, University of Edinburgh, 1974), 177. Carmichael's edition of Pufendorf first appeared in Glasgow in 1718, and a second edition was published in Edinburgh in 1724 while Hume was still a student there.2. The surviving correspondence between the two men from this period is to be found in The Letters of David Hume, ed. J.Y.T. Greig, 2 vols. (Oxford: Clarendon Press, 1932), I 32-35; 36-40; 45-48 (hereafter abbreviated as HL).3. The first detailed discussion of the 1745 election appeared in the introduction to David Hume, A Letter from a Gentleman to His Friend in Edinburgh, edited by Ernest C. Mossner and John V. Price (Edinburgh: Edinburgh University Press, 1967). This account has recently been challenged in Roger L. Emerson, "The 'Affair' at Edinburgh and the 'Project' at Glasgow: The Politics of Hume's Attempts to become a Professor," in Hume and Hume's Connexions, edited by M. A. Stewart and John P. Wright (Edinburgh: Edinburgh University Press, 1994), 1-22; and M. A. Stewart, The Kirk and the Infidel (Lancaster: Lancaster University Publications Office, 1995). For historically sensitive contextual analysis of Hume's philosophical relations with Hutcheson, see inter alia James Moore, "Hume and Hutcheson," in Stewart and Wright, 23-57, and M. A. Stewart, Warmth in the Cause of Virtue (Edinburgh: Edinburgh University Press, forthcoming).4. In January 1752, "Mr. Smith read an Account of some of Mr. David Hume's Essays on Commerce" to the Society, and Hume was elected a member in 1753; see Notices and Documents Illustrative of the Literary History of Glasgow, During the Greater Part of Last Century, edited by W. J. Duncan (Glasgow: T. D. Morison, 1886), 132-133. Hume's failed candidacy is discussed in Emerson, "The 'Affair' at Edinburgh," 14-16, and Ian Simpson Ross, The Life of Adam Smith (Oxford: Clarendon Press, 1995), 112-113. Smith's Glasgow colleague from 1751 to 1755, William Cullen, was also sympathetic to Hume's philosophy, as was John Millar, who was elected Professor of Law in 1761. On Cullen and Hume see J.R.R. Christie, "Ether and the Science of Chemistry: 1740-1790," in Conceptions of Ether: Studies in the History of Ether Theories 1740-1900, edited by G. N. Cantor and M.J.S. Hodge (Cambridge: Cambridge University Press, 1981), 90-96.5. David Hume to William Strahan, 26 October 1775, HL II 301.6. See, for example, The Works of Thomas Reid, D.D., edited by Sir William Hamilton, 4th ed. (Edinburgh: Maclachlan and Stewart, 1854), 30n; James McCosh, The Scottish Philosophy, Biographical, Expository, Critical, from Hutcheson to Hamilton (London: Macmillan, 1875), 36; James Veitch, "Philosophy in the Scottish Universities," Mind 2 (1877): 207-234 (209).7. John Rae, Life of Adam Smith (London and New York: Macmillan, 1895); William Robert Scott, Francis Hutcheson: His Life, Teaching and Position in the History of Philosophy (Cambridge: Cambridge University Press, 1900); idem., Adam Smith as Student and Professor (Glasgow: Jackson... (shrink)

Aristotle and the sea battle, by G. E. M. Anscombe.--Aristotle's different possibilities, by K. J. J. Hintikka.--On Aristotle's square of opposition, by M. Thompson.--Categories in Aristotle and in Kant, by J. C. Wilson.--Aristotle's Categories, chapters I-V: translation and notes, by J. L. Ackrill--Aristotle's theory of categories, by J. M. E. Moravcsik.--Essence and accident, by I. M. Copi.--Tithenai ta phainomena, by G. E. L. Owen.--Matter and predication in Aristotle, by J. Owens.--Problems in Metaphysics Z, chapter 13, by M. J. Woods.--The meaning (...) of agathon in the Ethics of Aristotle, by H. A. Prichard.--Agathon and eudaimonia in the Ethics of Aristotle, by J. L. Austin.--The final good in Aristotle's Ethics, by W. F. R. Hardie.--Aristotle on pleasure, by J. O. Urmson.--Bibliography (p. 335-41). (shrink)

Negative attitudes toward invertebrates are a deep-seated, visceral response among Western peoples. These internalized aversions toward insects and other terrestrial arthropods, both in general and specifically as a food source, subtly and systemically contribute to unsustainable global foodways. Insect cuisine is, for Westerners, emblematic of the alien, a threat to our psychological and cultural identity. Yet failure to embrace entomophagy prevents us from seeing the full humanity of those of other classes, races, and cultures, and leads to agricultural and food (...) policy decisions that fail in their objectives to improve nourishment for all people. Key to enabling the world’s peoples to live sustainably with the land are: awareness of the psychological and cultural barriers to a more insect-positive perspective embracing insects as a desirable food resource, understanding the processes by which those barriers are constructed, their negative consequences, and identifying strategies for transforming our attitudes. (shrink)

The aim of this investigation is to discuss the merits of the three radically divergent views as to the nature and function of the categories held by Kant, Ward and Alexander.

This dissertation seeks to contribute to research in the philosophy of social science. The study focuses upon select epistemological and ontological aspects of Hannah Arendt’s work from which methodological implications are drawn pertaining to sociology. Arendt, although critical of the sociology of her time, has become increasingly cited and influential for emerging sociological research and this study seeks to contribute to this by focusing upon the problem of novelty. The aim is to explore the philosophical and methodological implications of novelty (...) for social science by working through three case studies that are theoretically pivotal for social science—action, the ‘social’, and the self—in terms of novelty as expressed in Arendt’s writing. Arendt is critical of methodology and epistemology, aiming to draw her readers to ontological concerns outlined from her preoccupation with the 'world' and social reality. In this aim, Arendt seeks to distance herself from social sciences that she claims ignore human novelty in favour of reading social regularities, tendencies and similarities. Despite her disdain for method, Arendt suggests a anti-methodological 'method' (outlined in an overlooked footnote) for keeping trained upon and for dealing with novel, anomalous events. In the seed of this method lies a unique opportunity for social science to reassess and extend its methods, addressing this oversight and in so doing bring to light the novel social object as a legitimate subject of social research. (shrink)

The double slit experiment for a massive scalar particle is described using intuitionistic logic with quantum real numbers as the numerical values of the particle's position and momentum. The model assigns physical reality to single quantum particles. Its truth values are given open subsets of state space interpreted as the ontological conditions of a particle. Each condition determines quantum real number values for all the particle's attributes. Questions, unanswerable in the standard theories, concerning the behaviour of single particles in the (...) experiment are answered. (shrink)