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 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 his article ‘God and Probability’, 1 Hugh Mellor introduced the notion of the ‘bridge-hand fallacy’, allegedly committed by those who think they can appeal to probabilities in arguments for design. I should like to give this notion another airing, partly because of its recent criticism in two interesting books - R. G. Swinburne' The Existence of God and D. J. Bartholomew's God of Chance - and partly because it seems worth asking how it fares in relation to the most (...) recent examples of design argument, namely those which appeal to the so-called ‘anthropic principle’ in cosmology. (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)

Does the recent success of Podemos and Syriza herald a new era of inclusive, egalitarian left populism? Because leaders of both parties are former students of Ernesto Laclau and cite his account of populism as guiding their political practice, this essay considers whether his theory supports hope for a new kind of populism. For Laclau, the essence of populism is an “empty signifier” that provides a means by which anyone can identify with the people as a whole. However, the concept (...) of the empty signifier is not as neutral as he assumes. As I show by analyzing the role of race in his theory, some subjects are constituted in a way that prevents their unmediated identification with the people. Consequently, Laclau’s view should be read as symptomatic of the problems with populist logic if its adherents are to avoid reproducing its exclusions and practice a more inclusive politics. (shrink)

A comparative study of Zumel's and other scholastic theories concerning the influence of the understanding or reason upon the will.--L. K. B.

B L Curtis; Learning and Intentionality, Journal of Philosophy of Education, Volume 5, Issue 1, 30 May 2006, Pages 105–121, https://doi.org/10.1111/j.1467-9752.

B L Curtis; Learning and Intentionality, Journal of Philosophy of Education, Volume 5, Issue 1, 30 May 2006, Pages 105–121, https://doi.org/10.1111/j.1467-9752.

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)

On August 29, 1995, the United States District Court for the Northern District of Ohio ruled that certain practices of Blue Cross and Blue Shield of Ohio relating to the calculation of copayments on insurance claims violated provisions of ERISA, and thus BCBSO could be liable for unpaid benefits and breach of fiduciary duty ). According to BCBSO's Explanation of Benefits and Schedule of Benefits, beneficiaries were responsible for a 20 percent copayment for hospital charges, and the remaining 80 percent (...) of the Provider's Reasonable Charges would be paid by BCBSO. BCBSO negotiated with the hospitals to create discount agreements whereby the actual charge to BCBSO was less than 80 percent of the total amount of the hospital's charges. By this arrangement, BCBSO paid less than 80 percent of what patients were billed; concurrently, patients paid more than 20 percent of the amount ultimately paid to hospitals for their services. (shrink)