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)

BackgroundPreprint usage is growing rapidly in the life sciences; however, questions remain on the relative quality of preprints when compared to published articles. An objective dimension of quality that is readily measurable is completeness of reporting, as transparency can improve the reader’s ability to independently interpret data and reproduce findings.MethodsIn this observational study, we initially compared independent samples of articles published in bioRxiv and in PubMed-indexed journals in 2016 using a quality of reporting questionnaire. After that, we performed paired comparisons (...) between preprints from bioRxiv to their own peer-reviewed versions in journals.ResultsPeer-reviewed articles had, on average, higher quality of reporting than preprints, although the difference was small, with absolute differences of 5.0% [95% CI 1.4, 8.6] and 4.7% [95% CI 2.4, 7.0] of reported items in the independent samples and paired sample comparison, respectively. There were larger differences favoring peer-reviewed articles in subjective ratings of how clearly titles and abstracts presented the main findings and how easy it was to locate relevant reporting information. Changes in reporting from preprints to peer-reviewed versions did not correlate with the impact factor of the publication venue or with the time lag from bioRxiv to journal publication.ConclusionsOur results suggest that, on average, publication in a peer-reviewed journal is associated with improvement in quality of reporting. They also show that quality of reporting in preprints in the life sciences is within a similar range as that of peer-reviewed articles, albeit slightly lower on average, supporting the idea that preprints should be considered valid scientific contributions. (shrink)

This volume has 41 chapters written to honor the 100th birthday of Mario Bunge. It celebrates the work of this influential Argentine/Canadian physicist and philosopher. Contributions show the value of Bunge’s science-informed philosophy and his systematic approach to philosophical problems. The chapters explore the exceptionally wide spectrum of Bunge’s contributions to: metaphysics, methodology and philosophy of science, philosophy of mathematics, philosophy of physics, philosophy of psychology, philosophy of social science, philosophy of biology, philosophy of technology, moral philosophy, social and political (...) philosophy, medical philosophy, and education. The contributors include scholars from 16 countries. Bunge combines ontological realism with epistemological fallibilism. He believes that science provides the best and most warranted knowledge of the natural and social world, and that such knowledge is the only sound basis for moral decision making and social and political reform. Bunge argues for the unity of knowledge. In his eyes, science and philosophy constitute a fruitful and necessary partnership. Readers will discover the wisdom of this approach and will gain insight into the utility of cross-disciplinary scholarship. This anthology will appeal to researchers, students, and teachers in philosophy of science, social science, and liberal education programmes. 1. Introduction Section I. An Academic Vocation Section II. Philosophy Section III. Physics and Philosophy of Physics Section IV. Cognitive Science and Philosophy of Mind Section V. Sociology and Social Theory Section VI. Ethics and Political Philosophy Section VII. Biology and Philosophy of Biology Section VIII. Mathematics Section IX. Education Section X. Varia Section XI. Bibliography. (shrink)

Psychiatry is rapidly adopting digital phenotyping and artificial intelligence/machine learning tools to study mental illness based on tracking participants’ locations, online activity, phone and text message usage, heart rate, sleep, physical activity, and more. Existing ethical frameworks for return of individual research results (IRRs) are inadequate to guide researchers for when, if, and how to return this unprecedented number of potentially sensitive results about each participant’s real-world behavior. To address this gap, we convened an interdisciplinary expert working group, supported by (...) a National Institute of Mental Health grant. Building on established guidelines and the emerging norm of returning results in participant-centered research, we present a novel framework specific to the ethical, legal, and social implications of returning IRRs in digital phenotyping research. Our framework offers researchers, clinicians, and Institutional Review Boards (IRBs) urgently needed guidance, and the principles developed here in the context of psychiatry will be readily adaptable to other therapeutic areas. (shrink)

ObjectiveTo further delineate risk and resilience factors contributing to trajectories of mental health symptoms experienced by college students through the pandemic.Participantsn = 183 college students.MethodsLinear mixed models examined time effects on depression and anxiety. Propensity-matched subgroups exhibiting “increased” versus “low and stable” depression symptoms from before to after the pandemic-onset were compared on pre-pandemic demographic and psychological factors and COVID-related experiences and coping strategies.ResultsStudents experienced worsening of mental health symptoms throughout the pandemic, particularly during Fall 2020 compared with Fall 2019. (...) The propensity-matched subgroup exhibiting relative resilience reported less alcohol use prior to the pandemic, greater use of active coping strategies, and less of an impact on their college progress.ConclusionsResults point to several potential targets of screening and intervention to decrease residual impacts of the pandemic. (shrink)

In the life sciences, there is an ongoing discussion about a perceived ‘reproducibility crisis’. However, it remains unclear to which extent the perceived lack of reproducibility is the consequence of issues that can be tackled and to which extent it may be the consequence of unrealistic expectations of the technical level of reproducibility. Large-scale, multi-institutional experimental replication studies are very cost- and time-intensive. This Perspective suggests an alternative, complementary approach: meta-research using sociological and philosophical methodologies to examine researcher trust in (...) data. An improved understanding of the criteria used by researchers to judge data reliability will provide crucial, initial evidence on the actual scale of the reproducibility crisis and on measures to tackle it. (shrink)

It seems that, whereas a person's death needn't be a bad thing for him, it can be. In some circumstances, death isn't a "bad thing" or an "evil" for a person. For instance, if a person has a terminal and very painful disease, he might rationally regard his own death as a good thing for him, or at least, he may regard it as something whose prospective occurrence shouldn't be regretted. But the attitude of a "normal" and healthy human being (...) - adult or child - toward the prospect of his death is different; it is not unreasonable in certain cases to regard one's own death as a bad thing for oneself. If this is so, then the question arises as to why death is bad, in those cases in which it is bad. (shrink)

A book on history and theory which takes a fresh new look at the whole subject. It takes as its starting point historical ideas and thought about the past - rather than falling into the usual pattern of endlessly debating what history as a discipline does or should do. He doesn't take it for granted that history as a discipline has to exist at all - and looks at the influence and importance of historical ideas across the disciplines more generally. (...) This is quite a complex argument, but the book is written very clearly and takes on real empirical questions as well as theoretical ones. (shrink)

Astroturf organizations are fake grassroots organizations usually sponsored by large corporations to support any arguments or claims in their favor, or to challenge and deny those against them. They constitute the corporate version of grassroots social movements. Serious ethical and societal concerns underline this astroturfing practice, especially if corporations are successful in influencing public opinion by undertaking a social movement approach. This study is motivated by this particular issue and examines the effectiveness of astroturf organizations in the global warming context, (...) wherein large corporate polluters have an incentive to set up astroturf organizations to undermine the importance of human activities in climate change. We conduct an experiment to determine whether astroturf organizations have an impact on the level of user certainty about the causes of global warming. Results show that people who used astroturf websites became more uncertain about the causes of global warming and humans’ role in the phenomenon than people who used grassroots websites. Astroturf organizations are hence successful in promoting business interests over environmental protection. In addition to the multiple business ethics issues it raises, astroturfing poses a significant threat to the legitimacy of the grassroots movement. (shrink)

Because of the growing debate concerning the nature of Soviet-type societies, a symposium-review was organized around two important recent books on the subject. The following are discussions of either one or both of the following volumes: Ferenc Feher, Agnes Heller, Gyorgy Markus, Dictatorship over Needs, St. Martin's Press (New York, 1983). Victor Zaslavsky, The Neo-Stalinist State: Class, Ethnicity and Consensus in Soviet Society, M.E. Sharpe, Inc. (New York, 1982). In social analysis, effective explanations alternate “thick description” with “thin description” (...) Zaslavsky's The Neo-Stalinist State and Feher's, Heller's and Markus’ Dictatorship over Needs, can be seen to track “actually existine socialism” down the respective paths of “thick” and “think” analysis. (shrink)

In his paper ‘Scmantic Theory and Tacit Knowlcdgc’, Gareth Evans uscs a familiar kind of cxamplc in ordcr to render vivid his account of tacit knowledge. We arc to consider a finite language, with just one hundrcd scntcnccs. Each scntcncc is made up of a subjcct (a name) and a prcdicatc. The names are ‘a’, ‘b’, . . ., T. The prcdicatcs arc ‘F’, ‘G’, . . ., ‘O’. Thc scntcnccs have meanings which dcpcnd in a systematic way upon their (...) construction. Thus, all scntcnccs containing ‘a’ mean something about john; all scntcnccs containing ‘b’ mean something about Harry; all scntcnccs containing ‘F’ mean something about being bald; all scntcnccs containing ‘G’ mean something about being happy; and so 011. For this vcry simple language L, wc arc to consider various semantic theories. We could consider thcorics whosc dclivcranccs about wholc scntcnccs are of.. (shrink)

O presente artigo objetiva apresentar uma compreensão crítica do tempo presente, que se pode chamar de contemporaneidade. Nessa direção, as reflexões sobre esse momento histórico priorizaram os questionamentos filosóficos de Heidegger. Para interpretação mais ampla do pensamento heideggeriano, foi abordada, rapidamente, as concepções existenciais de homem e de mundo trazidas em sua obra “Ser e tempo”. Após essas considerações, a “Era da Técnica”, marcada pelo esquecimento do ser, foi tomada enquanto foco de discussão. Por fim, ressalta-se a inquietação não com (...) relação ao crescimento da técnica planetária, mas sim acerca do fato de o homem não compreender a dimensão e o sentido das transformações empreendidas por esta destinação; rejeitando, com isso, aquilo que tem de mais próprio, a condição de ser o único ser que reflete. (shrink)

A is for Alice and astronomers arguing about acceleration -- B is for Bernard's body-exchange machine -- C is for the Catholic cannibal -- D is for Maxwell's demon -- E is for evolution (and an embarrassing problem with it) -- F is for the forms lost forever to the prisoners of the cave -- G is for Galileo's gravitational balls -- H is for Hume's shades -- I is for the identity of indiscernibles -- J is for Henri Poincaré (...) and alternative geometries -- K is for the Kritik and Kant's kind of thought experiments -- L is for Lucretius' spear -- M is for Mach's motionless chain -- N is for Newton's bucket -- O is for Olbers' paradox -- P is for Parfit's person -- Q is for the questions raised by thought experiments quotidiennes -- R is for the rule-ruled room -- S is for Salvatius' ship, sailing along its own space-time line -- T is for the time-travelling twins -- U is for the universe, and Einstein's attempts to understand it -- V is for the vexed case of the violinist -- W is for Wittgenstein's beetle -- X is for xenophanes and thinking by examples -- Y is for counterfactuals and a backwards approach to history -- Z is for Zeno and the mysteries of infinity. (shrink)

Dès le prologue du Conte de l’Universitaire d’Oxford, l’Hôtelier impose les formes du conte qu’il attend de l’Universitaire, un « beau récit d’aventures ». Le thème de l’obéissance structure l’ensemble du conte. S’agit-il d’un plaidoyer en faveur de la soumission des femmes que la patience transformerait en saintes, en héroïnes dignes de figurer dans les récits hagiographiques? Que signifie l’effacement de Grisildis? Le narrateur cherche-t-il à peindre une Grisildis effacée ou plutôt à effacer ce type de femme admirable, certes, mais (...) peu authentique? Le conte ne suggère-t-il pas au contraire l’envers de ce décor, teinté de légendaire, ainsi que les coulisses d’un monde réel reflétant les mutations économiques et sociales de l’Angleterre du xive siècle. (shrink)

Fille de l’Encyclopédie (1751-1772, 28 vol.) de Diderot et d’Alembert, l’Encyclopédie méthodique (1782-1832, 212 vol.) de Panckoucke conserve la palme du gigantisme. Est-ce cette raison qui l’a fait passer dans l’oubli ou a-t-elle été elle-même dépassée tant par les événements historiques que par les développements scientifiques fulgurants? Pourtant, cette encyclopédie « par ordre de matières » revêt un intérêt considérable. En synthétisant ce moment particulier des savoirs liant mots et choses, elle représente un chaînon incontournable entre l’épistémè des Lumières et (...) celle du xixè siècle. La Méthodique met en évidence le circuit étendu de chaque science et son utilité sociale. Par ailleurs Panckoucke choisit les directeurs de Dictionnaires pour leur qualité d’expert et ils font autorité. Il faut aussi prendre en compte qu’entre Diderot et Wikipédia, il y a eu la Révolution française qui, dans le domaine de la pensée n’a rien changé ni aboli, mais qui « a changé les conditions d’exercice » au cœur desquelles travaille Naigeon, auteur des trois tomes du Dictionnaire de Philosophie ancienne et moderne présentés, sous forme d’extraits, dans ce Vol. IV de nos Anthologies. Malgré les tragédies individuelles de la Terreur, la voie vers la démocratie a été ouverte. Dans la conception de son Dictionnaire, Naigeon ne cache pas son militantisme athée qui fait qu’à la discussion de la dimension politique du religieux s’ajoute le point de vue de l’historien des sciences. L’éditrice, Claire Fauvergue, montre comment à travers le Discours préliminaire et les 14 articles recueillis qui vont de d’Alembert à Religieux-Irréligieux en passant par Condillac, Hobbes ou Diderot et Fréret, Naigeon renouvelle non seulement les sources de l’histoire de la philosophie mais aussi leur usage et leur analyse. Attentive à l’efficacité de son travail original d’auteur, veillant à la diversité de ses choix éditoriaux, privilégiant ce qui est représentatif du genre encyclopédique et de son évolution, Fauvergue illustre avec précision comment la figure de l’éditeur se mêle indissolublement à celle de l’auteur. (shrink)

"Qu'appelle-t-on "poétiser" à l'âge romantique? Telle est la question que cet essai philosophique sur Gérard de Nerval adopte comme fil conducteur pour interroger la puissance de l'art et le sens de la création au sein d'une modernité désenchantée. Tendue entre sublime et mélancolie, ruines et chimères, l'écriture nervalienne réfléchit son propre geste poétique en même temps qu'elle reconfigure nos représentations de l'existence. En philosophant avec la littérature, cet essai entend faire droit à la singularité d'une pensée qui se tisse à (...) même les formes, les tours et les détours des oeuvres de Gérard de Nerval."--Page 4 of cover. (shrink)

Dans quelles circonstances et pourquoi Robert K. Merton a-t-il rencontré l’idée de serendipity? Quelle place occupe-t-elle dans son œuvre? Cet article propose de reconstituer pas à pas l’histoire de cette rencontre, qui ne manque pas d’ironie ni de piquant. En elle-même « sérendipienne », la découverte accidentelle mais tellement féconde du mot serendipity ouvrit à Merton nombre de pistes de recherche au cours des années 1940. Le concept intrigant de la découverte fortuite qui – entre autres vertus – engendre des (...) résultats de nature à transformer la théorie promettait d’enrichir et de renouveler la connaissance objective. Mais la serendipity était plus qu’une recette heuristique à appliquer en science. Chez Merton, c’était aussi l’objet privilégié et « auto-exemplifiant » d’une sémantique sociologique des concepts, dont l’ambition est d’étudier les itinéraires des terminologies dans la culture. En retraçant la genèse de la recherche qu’il mena avec Elinor Barber sur l’histoire du mot et des significations parfois volatiles de la serendipity, on parviendra à saisir pourquoi ce thème revêtait pour Merton un double intérêt stratégique, à la fois épistémologique et autobiographique. On comprendra aussi pourquoi une nouvelle traduction en français du premier fragment d’article dans lequel le sociologue conceptualise la serendipity en 1948 est de bonne méthode sérendipienne. (shrink)

Cet article examine la concurrence entre des structures de gouvernance des entreprises. Il y est souligné qu’une panoplie de structures “constitutionnelles” peut être observée dans le cadre marchand et que cette variété a servi des objectifs transactionnels importants sur un plan historique. L’article met en contraste les approches coasienne et autrichienne de l’explication des structures de gouvernance. Nous examinons la tendance récente du déplacement de la propriété des entreprises vers les investisseurs par opposition aux arrangements coopératifs et “mutuels”. L ’ (...) a r gument a t ion sout i ent que l’intervention étatique peut être une explication importante des tendances récentes au Royaume Uni, notamment dans le domaine des institutions financières. Les suggestions selon lesquelles des modèles de gouvernance des entreprises par les “partenaires” devraient être introduits à travers l’intervention de l’Etat ignorent à la fois les coûts de transaction et l’importance d’assurer l’affectation du talent entrepreneurial en direction des ressources économiques.This paper considers competition between governance arrangements for firms. It is argued that a variety of ‘constitutional’ structures can be observed in the market and that historically this variety has served important transactional purposes. The Coasian and Austrian approaches to the explanation of governance arrangements are contrasted. Recent trends towards investor ownership of firms and away from co-operative and ‘mutual’ arrangements are considered. It is argued that government regulatory intervention may be an important explanation for recent trends in the UK, especially in the area of financial institutions. Suggestions that ‘stakeholder’ models of firm governance should be introduced through state intervention ignore considerations both of transactions costs and the importance of ensuring the allocation of entrepreneurial talent to the direction of economic resources. (shrink)