The recent speculation which I have in view is that which finds its inspiration in the great development of scientific discovery and scientific thought in our day. It would be impossible to range over the whole field. Moreover, the efforts which have been made to frame a comprehensive scheme of thought on the foundation supplied by science are those which are truly characteristic of our time. In recent years, science has been passing beyond the experimental stage, and also beyond the (...) limits which, in former times, made it departmental. The great conception of Evolution, and the intimate linking up of astronomy with chemistry and physics, and of chemistry and physics with physiology and biology, have quite altered our outlook on the universe. The mind of to-day passes from space-time to the electron, and from the electron to the structure of the cell, and from the cell to the living organism, with hardly a jolt. Not that the problems which mark the passage from stage to stage in this series have been solved, far from it; but that the different tages have so much the appearance of closing up into one continuous process that we seem to be approaching a view which will regard the whole as one unbroken development. No wonder that philosophic minds, among students and dreamers speculating on the mystery of the Universe, begin to think that some account of it, based on assured results of science, is becoming possible. (shrink)

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)

'Why did the window break when it was hit by the stone? Because the window is brittle and the stone is hard; hardness and brittleness are powers, dispositional properties or dispositions.' Dispositions are essential to our understanding of the world. This book is a record of the debate on the nature of dispositions between three distinguished philosophers - D. M. Armstrong, C. B. Martin and U. T. Place - who have been thinking about dispositions all their working lives. Their (...) distinctive accounts cover many of the issues surrounding dispositions such as the nature of mind, matter, universals, existence, laws of nature and causation. Dispositions illuminates this central topic in analytic philosophy and at the same time highlights deeper concerns of metaphysics. (shrink)