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)

v. 1. Nicomachean ethics. Politics. The Athenian Constitution. Rhetoric. On Poetics.--v. 2. Logic.--v. 3. Physics. Metaphysics. On the soul. Short physical treaties.--v. 4. On the heavens. On generation and corruption. Meteorology. Biological treatises.

This article is part of a For-Discussion-Section of Methods of Information in Medicine about the paper "Biomedical Informatics: We Are What We Publish", written by Peter L. Elkin, Steven H. Brown, and Graham Wright. It is introduced by an editorial. This article contains the combined commentaries invited to independently comment on the Elkin et al. paper. In subsequent issues the discussion can continue through letters to the editor.

The objective of the study was to investigate the relationship between childhood IQ of parents and characteristics of their adult offspring. It was a prospective family cohort study linked to a mental ability survey of the parents and set in Renfrew and Paisley in Scotland. Participants were 1921-born men and women who took part in the Scottish Mental Survey in 1932 and the Renfrew/Paisley study in the 1970s, and whose offspring took part in the Midspan Family study in 1996. There (...) were 286 offspring from 179 families. Parental IQ was related to some, but not all characteristics of offspring. Greater parental IQ was associated with taller offspring. Parental IQ was inversely related to number of cigarettes smoked by offspring. Higher parental IQ was associated with better education, offspring social class and offspring deprivation category. There were no significant relationships between parental IQ and offspring systolic blood pressure, diastolic blood pressure, cholesterol, glucose, lung function, weight, body mass index, waist hip ratio, housing, alcohol consumption, marital status, car use and exercise. Structural equation modelling showed parental IQ associated with offspring education directly and mediated via parental social class. Offspring education was associated with offspring smoking and social class. The smoking finding may have implications for targeting of health education. (shrink)

A substantial body of evidence suggests that autobiographical recollection and simulation of future happenings activate a shared neural network. Many of the neural regions implicated in this network are affected in patients with bipolar disorder , showing altered metabolic functioning and/or structural volume abnormalities. Studies of autobiographical recall in BD reveal overgeneralization, where autobiographical memory comprises primarily factual or repeated information as opposed to details specific in time and in place and definitive of re-experiencing. To date, no study has examined (...) whether these deficits extend to future event simulation. We examined the ability of patients with BD and controls to imagine positive, negative and neutral future events using a modified version of the Autobiographical Interview that allowed for separation of episodic and non-episodic details. Patients were selectively impaired in imagining future positive, negative, and neutral episodic details; simulation of non-episodic details was equivalent across groups. (shrink)

BackgroundIn the Canadian Alliance for Healthy Hearts and Minds (CAHHM) cohort, participants underwent magnetic resonance imaging (MRI) of the brain, heart, and abdomen, that generated incidental findings (IFs). The approach to managing these unexpected results remain a complex issue. Our objectives were to describe the CAHHM policy for the management of IFs, to understand the impact of disclosing IFs to healthy research participants, and to reflect on the ethical obligations of researchers in future MRI studies.MethodsBetween 2013 and 2019, 8252 participants (...) (mean age 58 ± 9 years, 54% women) were recruited with a follow-up questionnaire administered to 909 participants (40% response rate) at 1-year. The CAHHM policy followed a restricted approach, whereby routine feedback on IFs was not provided. Only IFs of severe structural abnormalities were reported.ResultsSevere structural abnormalities occurred in 8.3% (95% confidence interval 7.7–8.9%) of participants, with the highest proportions found in the brain (4.2%) and abdomen (3.1%). The majority of participants (97%) informed of an IF reported no change in quality of life, with 3% of participants reporting that the knowledge of an IF negatively impacted their quality of life. Furthermore, 50% reported increased stress in learning about an IF, and in 95%, the discovery of an IF did not adversely impact his/her life insurance policy. Most participants (90%) would enrol in the study again and perceived the MRI scan to be beneficial, regardless of whether they were informed of IFs. While the implications of a restricted approach to IF management was perceived to be mostly positive, a degree of diagnostic misconception was present amongst participants, indicating the importance of a more thorough consent process to support participant autonomy.ConclusionThe management of IFs from research MRI scans remain a challenging issue, as participants may experience stress and a reduced quality of life when IFs are disclosed. The restricted approach to IF management in CAHHM demonstrated a fair fulfillment of the overarching ethical principles of respect for autonomy, concern for wellbeing, and justice. The approach outlined in the CAHHM policy may serve as a framework for future research studies.Clinical trial registrationhttps://clinicaltrials.gov/ct2/show/nct02220582. (shrink)

Cultural norms may dictate how grief is displayed. The present study explores the display behaviours and rules in the bereavement context from a cross-cultural perspective. 86 German-speaking Swiss and 99 Chinese bereaved people who lost their first-degree relative completed the adapted bereavement version of the Display Rules Assessment Inventory. Results indicated that the German-speaking Swiss bereaved displayed more emotions than the Chinese bereaved. The Chinese bereaved, but not the German-speaking Swiss bereaved, thought that bereaved people should display more emotions than (...) they actually did when they were with their close others (but not when they were alone). Bereaved people endorsed more emotional expression “when alone” than “when with close others”, demonstrating a social disconnection tendency, which was more evident in the Chinese sample. Bereaved people endorsed more expression of positive emotions (e.g. affection/love) and less expression of powerful negative emotions (e.g. blame/guilt, anger) across cultures. Compared to their Chinese counterparts, the German-speaking Swiss sample indicated more actual expressions for most emotion types (i.e. joy/happiness, affection/love, sadness, anger, and denial) but thought bereaved people should express more joy/happiness and less blame/guilt. The results suggest that bereaved people’s display behaviours and rules are influenced by culture, situation, and type of emotion. (shrink)

MEDIEVAL LOGICS LAMBERT MARIE DE RIJK (ed.), Die mittelalterlichen Traktate De mod0 opponendiet respondendi, Einleitung und Ausgabe der einschlagigen Texte. (Beitrage zur Geschichte der Philosophie und Theologie des Mittelalters, Neue Folge Band 17.) Miinster: Aschendorff, 1980. 379 pp. No price stated. THE SEVENTEENTH CENTURY MARTA FATTORI, Lessico del Novum Organum di Francesco Bacone. Rome: Edizioni dell'Ateneo 1980. Two volumes, il + 543, 520 pp. Lire 65.000. VIVIAN SALMON, The study of language in 17th century England. (Amsterdam Studies in the Theory (...) and History of Linguistic Science, Series 111: Studies in theHistory of Linguistics, Volume 17.) Amsterdam: John Benjamins B.V., 1979.x + 218 pp. Dfl. 65. Theoria cum Praxi. Zum Verhaltnis von Theorie und Praxis im 17. und 18. Jahrhundert. (Akten des 111. Internationalen Leibnizkongress, Hannover, 12. bis 17.November 1977, Band 111: Logik, Erkenntnistheorie, Wissenschaftstheorie, Metaphysik, Theologie.) Wiesbaden: Franz Steiner Verlag, 1980. vii + 269 pp. DM 48. CLASSICAL AND NON-CLASSICAL LOGICS MICHAEL CLARK, The place of syllogistic in logical theory. Nottingham: University of Nottingham Press, 1980. ix + 151 pp. £3.00. A.F. PARKER-RHODES, The theory of indistinguishables. Dordrecht, Boston and London: D. Reidel Publishing Company, 1981. xvii + 216 pp. Dfl.90.00/$39.50. NICHOLAS RESCHER and ROBERT BRANDOM, The logic of inconsistency. Oxford:Basil Blackwell, 1980. x + 174 pp. f 11.50. MISCELLANEOUS J. ZELENY, The logic of Marx. Translated from the German by T. Carver. Oxford: Basil Blackwell, 1980. xcii + 247 pp. £12.50. FELIX KAUFMANN, The infinite in mathematics. Edited by Brian McGuinness. Introduction by E. Nagel. Translation from the German by Paul Foulkes. Dordrecht: Reidel, 1978. xvii + 235 pp. Dfl 85/$39.50 (cloth); Dfl 45/$19.95 (paper). PAMELA MCCORDUCK, Machines who think. San Francisco: W.H. Freeman and Company, 1979. xiv + 275 pp. $14.95. J. MITTELSTRASS (ed.), Enzyklopadie Philosophie und Wissenschaftstheorie Bd. 1 : A-G. Mannheim, Wien, Ziirich: Bibliographisches Institut, 1980. 835 pp. DM 128. (shrink)

Since the first selection of George Santayana's letters was published in 1955, shortly after his death, many more letters have been located. The Works of George Santayana, Volume V, brings together a total of more than 3,000 letters. The volume is divided chronologically into eight books of roughly comparable length. Book Two covers Santayana's first decade as a "freelance philosopher," following his resignation from Harvard University and move to Europe. Of particular interest is Santayana's continuing correspondence with the American philosopher (...) Charles Augustus Strong and with his sister Susana Sturgis de Sastre. Also included is correspondence with such notable figures as Bertrand Russell, Robert Seymour Bridges, Horace Kallen, and Logan Pearsall Smith. The correspondence covers Santayana's resignation from Harvard, his time in England during World War I, and comments on his philosophical work during this period. (shrink)

Johnstone, H. W., Jr. Rhetoric and communication in philosophy.--Smith, C. R. and Douglas, D. G. Philosophical principles in the traditional and emerging views of rhetoric.--Wallace, K. R. Bacon's conception of rhetoric.--Thonssen, L. W. Thomas Hobbes's philosophy of speech.--Walter, O. M., Jr. Descartes on reasoning.--Douglas, D. G. Spinoza and the methodology of reflective knowledge in persuasion.--Howell, W. S. John Locke and the new rhetoric.--Doering, J. F. David Hume on oratory.--Douglas, D. G. A neo-Kantian approach to the epistomology of judgment in (...) criticism.--Bevilacqua, V. M. Lord Kames's theory of rhetoric.--Brockriede, W. E. Bentham's philosophy of rhetoric.--Anderson, R. E. Kierkegaard's theory of communication.--Macksoud, S. J. Ludwig Wittgenstein, radical operationism and rhetorical stance.--Stewart, J. J. L. Austin's speech act analysis.--Torrence, D. L. A philosophy of rhetoric from Bertrand Russell.--Clark, A. Martin Buber, dialogue, and the philosophy of rhetoric.--Bennett, W. Kenneth Burke--a philosophy in defense of un-reason.--Dearin, R. D. The philosophical basis of Chaim Perelman's theory of rhetoric. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:Buddhist-Christian Studies 21.1 (2001) v-vi [Access article in PDF] In Memoriam: Wilfred Cantwell Smith Wilfred Cantwell Smith, a Canadian who taught for most of the first half of his career at McGill University in Montreal and for most of the second half at Harvard, died February 7, 2000, in his native Toronto at the age of eighty-three. His wife and companion of sixty years, Muriel, survives him, (...) as do five children and a dozen grandchildren.Smith, a Protestant Christian and clergyman, played an influential role among both academics and church bodies in advocating open dialogue and personal encounter with the adherents of diverse religious traditions. As one of his students, Professor John Ross Carter of Colgate University, put it, "Before I met Wilfred, I had studied Buddhism as a system. Under him, I came to appreciate the faith of Buddhists as persons."As an undergraduate, Smith studied Middle Eastern languages at the University of Toronto. He then studied theology in Cambridge, England, and taught during the early 1940s at Forman Christian College, Lahore, in what was then India but is now Pakistan. He became involved in the vital contemporary life of Muslims, and in the Hindu-Muslim-Sikh interface in the Punjab. The partition of India along communal lines in 1947 reinforced his strong sense of the moral urgency of interreligious understanding.After completing a Ph.D. degree at Princeton University with a dissertation on modern Islam, Smith took up the chair of comparative religion in McGill University's Faculty of Divinity and soon organized McGill's Institute of Islamic Studies, which he directed until 1963. The institute was innovative in two respects. First, it treated Islam as the faith of millions in southern Asia today, where the numerical majority of Muslims live, in contrast with the emphasis of most Orientalist scholarship on classical Arabic, Persian, and Turkish literature. Second, it strove to include roughly equal numbers of Muslims and Westerners in both its faculty and its student body.Though he had already made seminal contributions to comparative studies, Smith moved fully into that realm when in 1964 he took over the directorship of Harvard Divinity School's Center for the Study of World Religions, and later, of Harvard's entire graduate program in religion in arts and sciences. Through two decades, until his 1984 retirement, the world religions Ph.D. graduates emerging from Harvard, including a significant cohort of specialists in Buddhist studies, were inspired by Smith to focus on the faith dimension of the traditions they studied.Religious bodies turned to Smith for scholarly advice. To take one important example, he served in 1967 on a commission on world mission of the United Church of Canada. As a result of his input, the commission's report, adopted by the denomination, [End Page v] affirmed God to be working creatively and redemptively in the religious traditions of humankind. Some view this as the first declaration by any church to go so far in the entire history of Christianity.Numerous responsibilities and honors came to Smith. He became president of practically every organization to which he belonged, such as the American Academy of Religion, the American Society for the Study of Religion (which he said was his favorite), the Canadian Society for the Study of Religion, and the Canadian Theological Society. His writings have been translated into many languages, as diverse as Spanish, Turkish, Urdu, and Korean. He received a dozen honorary degrees, was elected to the Royal Society of Canada, and less than a month before the end of his life was inducted in a special bedside ceremony as an Officer of the Order of Canada, the nearest honor that country has to a title of nobility awarded for merit.Smith was primarily a historian, ever fascinated by process and change. He observed it not only in the societies and traditions of world culture, but in the conceptual vocabulary with which we describe it. His landmark book, from this point of view, is TheMeaning and End of Religion(1963), in which he traced both the emergence of the view of particular traditions... (shrink)