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)

Public health and service delivery programmes, interventions and policies (collectively, ‘programmes’) are typically developed and implemented for the primary purpose of effecting change rather than generating knowledge. Nonetheless, evaluations of these programmes may produce valuable learning that helps determine effectiveness and costs as well as informing design and implementation of future programmes. Such studies might be termed ‘opportunistic evaluations’, since they are responsive to emergent opportunities rather than being studies of interventions that are initiated or designed by researchers. However, current (...) ethical guidance and registration procedures make little allowance for scenarios where researchers have played no role in the development or implementation of a programme, but nevertheless plan to conduct a prospective evaluation. We explore the limitations of the guidance and procedures with respect to opportunistic evaluations, providing a number of examples. We propose that one key missing distinction in current guidance is moral responsibility: researchers can only be held accountable for those aspects of a study over which they have control. We argue that requiring researchers to justify an intervention, programme or policy that would occur regardless of their involvement prevents or hinders research in the public interest without providing any further protections to research participants. We recommend that trial consent and ethics procedures allow for a clear separation of responsibilities for the intervention and the evaluation. (shrink)

The ratio of index- and ring-finger lengths is thought to be related to prenatal androgen exposure, and in many, though not all, populations, men have a lower average digit ratio than do women. In many studies an inverse relationship has been observed, among both men and women, between 2D:4D ratio and measures of athletic ability. It has been further suggested that, in hunter-gatherer populations, 2D:4D ratio might also be negatively correlated with hunting ability, itself assumed to be contingent on athleticism. (...) This hypothesis has been tested using endurance running performance among runners from a Western, educated, and industrialized population as a proximate measure of hunting ability. However, it has not previously been tested among actual hunter-gatherers using more ecologically valid measures of hunting ability and success. The current study addresses this question among Tanzanian Hadza hunter-gatherers. I employ a novel method of assessing hunting reputation that, unlike previous methods, allows granular distinctions to be made between hunters at all levels of perceived ability. I find no statistically significant relationship between digit ratio and either hunting reputation or two important hunting skills. I confirm that Hadza men have higher mean 2D:4D ratios than men in many Western populations. I discuss the notion that 2D:4D ratio may be the consequence of an allometric scaling relationship between relative and absolute finger lengths. Although it is difficult to draw clear conclusions from these results, the current study provides no support for the theorized relationship between 2D:4D ratio and hunting skill. (shrink)

BACKGROUND: Hallucinations and delusions that complicate Parkinson’s disease could lead to nursing home placement and are linked to increased mortality. Cognitive impairments are typically associated with the presence of hallucinations but there are no data regarding whether such a relationship exists with delusions. OBJECTIVE: We hypothesized that hallucinations would be associated with executive and visuospatial disturbance. An exploratory examination of cognitive correlates of delusions was also completed to address the question of whether they differ from hallucinations. METHODS: 144 PD subjects (...) completed a neuropsychological battery to assess cognition and the SAPS to examine psychosis. Correlational analyses assessed associations between hallucinations and delusions with cognitive domains. RESULTS: 48 subjects reported psychotic symptoms: 25 experienced hallucinations without delusions, 23 had symptoms dominated by delusions. Severity and/or number of hallucination subtypes were significantly correlated with lower scores in language, memory, attention, executive functioning, and visuospatial ability. Correlations with delusions were non-significant. Tests of differences in the size of the correlations between groups revealed a significant relationship between language and visuospatial performance with hallucinations. CONCLUSIONS: Cognitive correlates of hallucinations and delusions appear to be different in PD, suggesting distinct pathogenic mechanisms and possibly anatomical substrates. Hence, delusions may not share the same associations with dementia as hallucinations. Since this is a new finding, further studies will be needed to confirm our results. (shrink)

Anagrams and syllabic wordplay of the kind championed by Frederick Ahl in his Metaformations have not always been favourably received by scholars of Latin poetry; I would hesitate to propose the following instance, were it not for the fact that its occurrence seems peculiarly apposite to the context in which it appears. That Roman poets were prepared to use such techniques to enhance the presentation of an argument by exemplifying its operation at a verbal level is demonstrated by the famous (...) passage of Lucretius in which the poet seeks to illustrate the tendency of semina … ardoris to create fire in wood by the literal presence of elements from the word for ‘fires’ in that denoting wood. A similar conception may underlie the association insinuated by the love elegists between amor and mors, suggesting that death is somehow ‘written into’ love: so Propertius declares laus in amore mori, while Tibullus appears to point to the lurking presence of death in the pursuit of love in the lines interea, dum fata sinunt, iungamus amores: | iam ueniet tenebris Mors adoperta caput – so swift and unexpected is death's approach that it is already present in aMOReS in the preceding line. Ovid's awareness of the poetic potential of this kind of play is fully exhibited in his celebrated account of Echo and Narcissus in Metamorphoses 3, where the subject matter gives the poet ample scope to exploit the humorous and pathetic possibilities afforded by Echo's fragmented repetitions of the frustrated entreaties of her beloved. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:MEISTER ECKHART AND THE NEOPLATONIC HERITAGE: THE THINKER'S WAY TO GOD RICHARD Wooos, O.P. Loyola University of Ohioago Ohicago, Illinois IN BOTH HIS LIFE rand preaching, Meister Eokrhart's " way" was pre-eminently.a spirituality of the mind. The srpeoulat:ive inqui.rires.and p:roibings thaJt animate his iSChD'l-·arly woliks 1also f!:>iervrude his sermons ·and treatisies, while a pastoral, homiletic inrberrtion iieciproca:1ly permeates the scholarly.worrks, particularly in regard to.the Meister'1s fascination with rthe Woil1d. (...) Heinrich Deni:fle, 1who disonviered and first commented upon Eckhart's Laitin writings in the 1880s, concluded that the Meister faclmd the clarity of conception and precision of expression characteristic of the great scholastic figmes who preoeded him, partiou1ady Albert the Grea:t 1and 'lihomas Aquinrus.1 B:ut more reoent Eckhart scholars have increasingly •argued that Denifle's oonoern to :ve£ute uncritically inflated characteriz,ations of Eckhart's philosophloa:l genius, notrubly that of Wilhelm Preger,.led him to undel'V'alue and indeed misrepvesen:t •the Meister's ireal goal a;nd bme achievement. Indeed, tto the modern critical eye, aided :by a oontury 1 "Eckhart ein unklarer Denker war, der sich der Consequenzen seiner Lehrer resp. seiner ausdruckweise nicht bewusst war. Gerade bei den schwierigen Lehrpunkten, wo Klarheit und Scharfe der Begriffe und des Ausdrucks mehr als je geboten ist, tritt dies zu Tage. Gerade in den entscheidenden Momenten verlasst ihn die Klarheit.... Eckhart besass aber nicht die geistige Begabung iiber die Scholastik hinauszugeben und doch innerhalb der Granzen der Wahrheit zu bleiben." "Meister Eckharts lateinische Schriften, und die Grundanschauung seiner Lehre," in A.rahiv fii,r Literatur unCl Kirchengeschichte Cles Mittelalters, ed. H. Denifie and Franz Ehrle (Graz: Akademische Druck u. Verlagsanstalt, 1956), vol. 2, pp. 482, 521. 609 610 RICHARD WOODS, O.P. of ]urbher di:s:cioverieis 1rund study, " the scholastic Eckhart is an original.and spooulaxbivie til:rintker, 1and not only a spirit's itineriary fa~om.aJJJd ha:ck to its eternail. Sourioe-4hie Ohristian NoopLatonic schema th.at Eckhart im.heri'bed room St. Albert tb!e Greait rund, 1behind him, Hugh and Richa;rid of St. Victo:r, Thomas Ga1lus, John Sarraoenus, John Soottus Eriugena, Diornysiius the Areop1aigibe, P!l.'odus, and, penultimrutely, Pilotinus!himself. For thls gre:art theoa Meister Eckhart: Die deutschen und lateinischen Werke: Herausgegeben im Auftrage der Deutschen Forschungsgemeinschaft, 11 Vols. to date (Stuttgart and Berlin: Verlag W. Kohlhammer, 1958-). German sermons will be identified hereafter by their number in the Deutsche Werke and, for English translation, by the corresponding page number in the Walshe edition. 9 " Eine Koiner Handscrift mit lateinischen Eckhart-Exzerpten," Archivum Fratrum Praedicatorum 31 (1961) : 204-12. In volume three of his edition, Walshe includes a translation of a fragment of one of Eckhart's sermons discovered by Prof. Kurt Ruh in 1967 and published in the Zeitschrift fii,r deutohes Aitertum 111 (1982) : 219-25. See ed. cit., pp. 131-35. ECKHART AND NEOPLATONISM 618 ~ogical tradition, liecently examined in some detail iby John Macquarrie alllld Andrew Louth, stretches hack evoo £artlier to tbie Oappadocian Fraithe'I"s, Origien, Philo, :and at the source, Pilato.in Smee the 1app1e1amance of Eoklhamt'1s more aoadiemic Laltin wiorrks, op;inion has heen divided as 1 00 their importance :velative ibo the more familiar German sermons iand tT1eatises for understarndmg the Meister~s authentic tooching. Some recent commenibato 'l.1s 1 sti1l 1:Jend to favor the lattier aJ.moot enti'11ely, even wihile acknOW11edging t:hie impo'11tooce of the forn11er; some favor the Latin.11 Critical opinion :seems 'bo have turned in the direction of remphrusizing the importalllice of both.the Latin and the German :works in 01der 1bo unders:tand the whole Eckhartthe teacher and the p:veacheT.12 But to understand to what extent Ed.mart ias,a tlheologian, philosopher, arrd mystic was indebted to Obrisltian Nooplatmrism it is raliso n:ecess1acy to see him in the oonteJct of his,w;orks, his method, and his scholarly and apostolic career. The Scholar and His Temper While Echltart had ra ik!een phi1osorphica1 temperament, he did not 1rus,a rule compose racrudemic 1weatises. Ratiher, he scatltJeTed... (shrink)

Books reviewed in this article: The Anchor Bible Dictionary. Edited by David Noel Freedman with Gary A. Herion, David F. Graf, John David Pleins. The Gospel of Matthew. By Daniel J. Harrington. Paul: An Introduction to his Thought. By C. K. Barrett. A Radical Jew: Paul and the Politics of Identiy. By Daniel Boyarin. New Testament Theology. By G. B. Caird, completed and edited by L. D. Hurst. The Fatherhood of God from Origen to Athanasius. By Peter Widdicombe. Dieu et (...) le Christ selon Grégoire de Nysse. By Bernard Pottier. Eucharistic Presence: A Study in the Theology of Disclosure. By Robert Sokolowski. Theological Hermeneutics: Development and Significance. By Werner Jeanrond. Theologie aus Efahrung der Gnade. Annäherungen an Karl Rahner: Edited by Mariano Delgado and Mathias‐Lutz Bachmann. Bernhard Welte's Fundamental Theological Approach to Christology.. By Anthony J. Godzieba. Sacred Identity: Exploring a Theology of the Person. By Jane Kopas. A Salvation Audit. By Colin Grant. Medical Ezhics: Sources Of Catholic Teachings, Second Edition. Edited by Kevin O'Rourke and Philip Boyle. Mission and Conversion: Proselytizing in the Religious History of the Roman Empire. By Martin Goodman. Literacy and Power in the Ancient World. Edited by Alan K. Bowman and Greg Woolf. St Cyril of Alexandria: The Christological Controversy. Its History, Theology and Texts. By John A. McGuckin. Ambrose of Milan: Church and Court in a Christian Capital. By Neil B. McLynn. Basil of Cuesareu. By Philip Rousseau. Augustine. By Mary T. Clark. Irenaeus. By Dennis Minns. Divine Heiress: The Virgin Mary and the Creation of Christian Constantinople. By Vasiliki Limberis. The Irish Tradition in Old English Literature. By Charles D. Wright. Relics, Apocalypse and the Deceils of History: Ademar of Chabannes, 989–1034. By Richard Landes. Huguccio: The Life, Works, and Thought of a Twelfth‐Centuy Jurist. By Wolfgang P. Müller. The Presence of God: A History of Western Christian Mysticism, Volume II: The Growth of Mysticism. By Bernard McGinn. Preaching the Crusades: Mendicant Friars and the Cross in the Thirteenth Century. By Christoph T. Maier. Mary Ward: A World in Contemplation. By Henriette Peters. The Letters of Teilhard de Chardin and Lucile Swan. Edited by Thomas M. King and Mary Wood Gilbert. Pseudo‐Marry: By John Donne. Edited, with an Introduction and Commentary, by Anthony Raspa. Donne and the Politics of Conscience in Early Modern England. By M. L. Brown. The Caroline Captivity of the Church: Charles 1 and the Remoulding of Anglicanism. By Julian Davies. Érudition et religion aux XVIIe et XVIIIe siécles. By Bruno Neveu. Cardinal Lavigerie: Churchman, Prophet and Missionary. By François Renault. Dom Columba Marmion: A Biography By Mark Tierney. Christian Mission in the Twentieth Century. By Timothy Yates. Religion in Africa: Experience and Expression. Edited by Thomas D. Blakely, Walter E. A. van Beek and Dennis Thomson. (shrink)

Books Reviewed in this Article: Theological Investigations, Vol. XVIII: God and Revelation. By Karl Rahner. Pp.vi, 304, London, Darton, Longman and Todd, 1984, £18.50. Theological Investigations, Volume XIX: Faith and Ministry. By Karl Rahner. Pp.vi, 282, London, Darton, Longman & Todd, 1984, £18.50. Theological Investigations: Volume XX: Concern for the Church. By Karl Rahner. Pp.vi, 191, London, Darton, Longman & Todd, 1981, £14.50. Concise Theological Dictionary. Edited by Karl Rahner and Herbert Vorgrimler. Pp.541, London, Burns & Oates, 1983, £12.50. A (...) New Dictionary of Christian Theology. Edited by Alan Richardson and John Bowden. Pp.xvii, 614, London, SCM Press, 1983, £19.50. The God of Forgiveness and Healing in the Theology of Karl Rahner. By J.N. King, Pp.93, Washington, University Press of America, 1982, $17.50, $6.75. In Search of Humanity, A Theological and Philosophical Approach. By John Macquarrie. Pp.vii, 280, London, SCM Press, 1982, £8.50. Faith and the Mystery of God. By Maurice Wiles. Pp.viii, 146, London, SCM Press, 1982, £4.50. Trinity and Temporality: The Christian Doctrine of God in the Light of Process Theology and the Theology of Hope. By John J. O'Donnell. Pp.xii, 215, Oxford University Press, 1983, £15.00. The Cosmic Christ in Origen and Teilhard de Chardin: A comparative Study. By James A. Lyons and edited by Maurice Wiles. Pp.xii, 236, Oxford University Press, 1982, £13.50. Grounded in Love: Sacramental Theology in an Ecumenical Perspective. By Frans Josef van Beeck. Pp.x, 151, Washington, University Press of America, 1982, $19.50, $9.25. Justification: The Author's First Book reissued with a New Introductory Chapter and the Original Response of Karl Barth. By Hans Küng. Pp.xlvi, 332, London, Burns and Oates, 1982, no price given. Reality and Evangelical Theology. By T.F. Torrance. Pp.174, Philadelphia, Westminster Press, 1982, $8.95. The Quest for the Historical Israel: Reconstructing Israel's Early History. By George W. Ramsey. Pp.xiv, 193, London, SCM Press, 1982, £5.50. Cantico del Cantici: Interpretatio Ludica. By Enrica Salvaneschi. Pp.140. Genoa, II Melangolo, 1982, 15, 000 Lire. Love Lyrics from the Bible: A Translation and Literary Study of the Song of Songs. By Marcia Falk. Pp.142, Sheffield, Almond Press, 1982, £14.95, £5.95. Old Testament Wisdom: An Introduction. By James L. Crenshaw. Pp.286, London, SCM Press, 1982, £5.95. The Sciences and Theology. Edited by A.R. Peacocke. Pp.xviii, 309, Stocksfield, Oriel Press, 1982, £14.00. Vision and Character: A Christian Educator's Alternative to Kohlberg. By C.R. Dykstra. Pp.viii, 160, Leominster, Fowler Wright Books, 1981, £4.45. Aristotle's Eudemian Ethics, Books I, II & III. Translated with a commentary by Michael Woods. Pp.xii, 234, Oxford, Clarendon Press: Oxford University Press, 1982, £11.50. Kant's Theory of Mind: An Analysis of the Paralogisms of Pure Reason. By Karl Ameriks. Pp.ix, 314, Oxford, Clarendon Press, 1982, £15.00. Heidegger's‘Being and Time’and the Possibility of Political Philosophy. By Mark Blitz. Pp.260, Ithaca, Cornell University Press, 1981, £13.75. Symbol as Sense: New Approaches to the Analysis of Meaning. Edited by Mary Le Cron Foster and Stanley H. Brandes. Pp.xvi, 416, New York, Academic Press, 1980, £19.60. The God Within. By Harry R. Klocker. Pp.x, 147, Washington, University Press of America, 1982, $19.00, $9.25. The Philosophical Frontiers of Christian Theology: Essays Presented to D.M. MacKinnon. Edited by Brian Hebblethwaite and Stewart Sutherland. Pp.ix, 252, Cambridge University Press, 1982, £17.50. Jews, Pagans and Christians in Conflict. By David Rokeah. Pp.232, Jerusalem, The Magnes Press, The Hebrew University, Leiden; E.J. Brill, 1982, 94 gld. Religion, Law, and the Growth of Constitutional Thought 1150–1650. By Brian Tierney. Pp.xi, 114, Cambridge University Press, 1982, £12.50. St John of the Cross: The Life and Thought of a Christian Mystic. By Alain Cugno. Pp.vi, 153, London, Burns & Oates, 1982, £6.95. Meister Eckhart: The Essential Sermons, Commentaries, Treatises and Defense. Translated by Edmund Colledge and Bernard McGinn. Pp.xviii, 360, London, SPCK, 1981, £8.50. Francisco de Osuna: the Third Spiritual Alphabet. Translated by May E. Giles. Pp.xvi, 624, London, SPCK, 1981, £12.50. Rome and the Anglicans. Edited with a Postscript by Wolfgang Haase. Pp.301, Berlin, Walter de Gruyter, 1982, 138 DM. The Westminster Confession in the Church today: Papers Prepared for the Church of Scotland Panel on Doctrine. Edited by Alasdair I.C. Heron. Pp.vii, 154, Edinburgh, Saint Andrew Press, 1982, £4.00. Essaying Montaigne: A Study of the Renaissance Institution of Writing and Reading. By John O'Neill, Pp.ix, 244, London, Routledge and Kegan Paul, 1982, £12.50. Rousseau after 200 years: Proceedings of the Cambridge Bicentennial Colloquium. Edited by R.A. Leigh. Pp.xv, 299, Cambridge University Press, 1982, £30.00 An American Experience of God: The Spirituality of Isaac Hecker. By John Farina. Pp.xii, 217, New York, Paulist Press, 1981, $11.95. Hecker Studies: Essays on the Thought of Isaac Hecker. Edited by John Farina. Pp.vii, 243, New York, Paulist Press, 1983, $6.95. (shrink)

© The Authors 2017. Published by Oxford University Press on behalf of The Analysis Trust. All rights reserved. For Permissions, please email: [email protected] Clark is usually among the first in philosophy to ride a new and important wave on the frontiers of cognitive science research. His Microcognition and Associative Engines chronicled connectionism, Being There explored embodied cognition, Natural Born Cyborgs deals with BCIs and environmental and technological scaffolding, and Supersizing the Mind is an extended argument for extended minds. Clark's latest, (...) showcases his new enthusiasm about predictive coding, a computational framework for understanding cognition that is generating more excitement and controversy across diverse areas of cognitive science than an offshore wind at Maverick’s does among the boarding elite....Clark is a master at taking complex ideas in cognitive science and conveying them in less technical fashion to a wide audience, doing so with panache and wit.... (shrink)

Publicity for (and laterly increased economic stringency which makes more likely), failures of care in the NHS engender concern for care quality while its assurance remains the subject of a fragmented and unhelpful literature. A selective attempt is made to examine some underlying principles by posing and answering three questions. What is the quality of care? What basic principles must be followed in defining `standards'? How then may quality be assured? Any definition of care must be multi-faceted and in common (...) use pervaded with the patients' pre-occupation with a search for cures. Nevertheless, it is argued that there are gains in restricting the technical use of the term `care' to those systematic processes of health services and their culture which impinge on the personal experience of patients and which fashion their response. In contemporary society care ought to be designed to restore and enhance the independence, dignity and choice of the patient. Although there is a contrary tendency to abandon problems of care to the professionals, standards for care should be judged ultimately not from the specialised professional but from the viewpoint of lay people whose behaviour in the outside world fashions those norms by which independence, dignity and choice are judged. A number of difficulties in identifying and securing improvements in care are discussed. In particular, it is argued that such is the interdependence of the style of management of an institution and the style of care it provides that enforcement of high quality care is likley to be a contradiction in terms. Only trained and sensitive staff can act intuitively and pre-emptively to prevent even incipient deterioration in care. They cannot carefully foster at all times the independence and dignity of their patients unless they are treated in a similar way as professional employees. As an initial step in improving the quality of care a simple start is urged upon implementing an inventory of checks. These are designed to establish the identification and operation of health care policies and practices which give appropriate recognition to the characteristics of care that patients and public expect, coming as they do from a lay rather than professional world. The article concludes with an appropriate inventory of questions to be put to professionals by those laymen who are increasingly imported into health care management through community representation (in CHCs) and staff participation (in joint consultation) and whose interest and concern should be harnessed appropriately. (shrink)

The greatest contemporary challenge in the arena of cognitive neuroscience concerns the relation between consciousness and the brain. Over recent years the focus of work in this area has switched from the analysis of diverse spatial regions of the brain to that of the timing of neural events. It appears that two conditions are necessary in order for neural events to become correlated with conscious experience. First, the firing of assemblies of neurones must achieve a degree of coherence, and, second, (...) reflexive (i.e. top-down, or reentrant) neural pathways must be activated. It does not, of course, follow that such neural activity causes consciousness; it may be, for example, that the neural activity formats the brain to interact with consciousness. The latter possibility is suggested by analysis of mystical texts suggesting that coherence and reflexivity constitute the conditions for the influx of “spirit.” Kabbalistic sources, for example, describe a hierarchy of “brains” in the human and divine realms through which the principles of coherence and reflexivity operate. Whilst the ontological assumptions of such a scheme place it beyond the realm of psychology, parallels with the picture deriving from the contemporary cognitive neuroscience of consciousness are striking. (shrink)

There is now a rapidly expanding population of interlinked developmental biology databases on the World Wide Web that can be readily accessed from a desk‐top PC using programs such as Netscape or Mosaic. These databases cover popular organisms (Arabidopsis, Caenorhabditis, Drosophila, zebrafish, mouse, etc.) and include gene and protein sequences, lists of mutants, information on resources and techniques, and teaching aids. More complex are databases relating domains of gene expression to embryonic anatomy and these range from existing text‐based systems for (...) specific organs such as kidney, to a massive project under development, that will cover gene expression during the whole of mouse embryogenesis. In this brief article, we review selected examples of databases currently available, look forward to what will be available soon, and explain how to gain access to the World Wide Web. (shrink)