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)

The need for informed analyses of health policy is now greater than ever. The twelve essays in this volume show that public debates routinely bypass complex ethical, sociocultural, historical, and political questions about how we should address ideals of justice and equality in health care. Integrating perspectives from the humanities, social sciences, medicine, and public health, this volume illuminates the relationships between justice and health inequalities to enrich debates. Understanding Health Inequalities and Justice explores three questions: How do scholars approach (...) relations between health inequalities and ideals of justice? When do justice considerations inform solutions to health inequalities, and how do specific health inequalities affect perceptions of injustice? And how can diverse scholarly approaches contribute to better health policy? From addressing patient agency in an inequitable health care environment to examining how scholars of social justice and health care amass evidence, this volume promotes a richer understanding of health and justice and how to achieve both. -/- The contributors are Judith C. Barker, Paula Braveman, Paul Brodwin, Jami Suki Chang, Debra DeBruin, Leslie A. Dubbin, Sarah Horton, Carla C. Keirns, J. Paul Kelleher, Nicholas B. King, Eva Feder Kittay, Joan Liaschenko, Anne Drapkin Lyerly, Mary Faith Marshall, Carolyn Moxley Rouse, Jennifer Prah Ruger, and Janet K. Shim. (shrink)

This expanded edition of C L Hardin's ground-breaking work on colour features a new chapter, 'Further Thoughts: 1993', in which the author revisits the dispute ...

One dark and rainy night, Yuso sexually assaults and tortures Zelan. In escaping from the scene of his crime, he falls heavily and becomes an impotent paraplegic. Instead of treating his fate as divine retribution for his wicked acts, Yuso sees it as sheer bad luck. He shows no remorse for what he has done, and vainly hopes that he will recover his powers, which he now treats as involuntarily hoarded resources to be used on less rainy days. In the (...) presence of others, he pretends that he has turned over a new leaf. He asks for religious and educational books, hoping to make up for his poor education and deprived social background. But he immediately discards them when he is alone in favor of the pornographic magazines which he has bribed a nurse to smuggle in for him. His deception and various obscene acts committed in the hospital are exposed; by the time he comes up for trial, everyone knows that he is still a lustful, sadistic, and unrepentant man. Most retributivists have a sufficient justification for punishing Yuso independently of the social consequences of his punishment. Two features of the case might cause some difficulties. First, Yuso has already experienced considerable suffering and deprivation both before and after his crime, and retributivists might disagree about the relevance of the suffering to his punishment. Secondly, Yuso is unrepentant, and it is unlikely that punishment will change him. This might, as we shall see, create a problem for those who think that the justifying aim of punishment is the moral reform of the offender. (shrink)

This detailed and sympathetic, but not uncritical, study of On Liberty' argues for the general consistency and coherence of Mill's defence of individual liberty, but maintains that there are significant non-utilitarian elements in his arguments.

What ecological advantages do animals gain by being able to detect, extract and exploit wavelength information? What are the advantages of representing that information as hue qualities? The benefits of adding chromatic to achromatic vision, marginal in object detection, become apparent in object recognition and receiving biological signals. It is argued that this improved performance is a direct consequence of the fact that many animals' visual systems reduce wavelength information to combinations of four basic hues. This engenders a simple categorical (...) scheme that permits a rich amount of sensory information to be rapidly and efficiently employed by cognitive machinery of limited capacity. (shrink)

Contingent valuation of the environment has proven popular amongst environmental economists in recent years and has increased the role of monetary valuation in public policy. However, the underlying economic model of human psychology fails to explain why certain types of stated behaviour are observed. Thus, good scope exists for interdisciplinary research in the area of economics and psychology with regard to environmental valuation. A critical review is presented here of some recent research by social psychologists in the US attempting to (...) explain stated behaviour in contingent valuation. Attitudinal scales have been used to analyse the role of ecocentric, biocentric and altruistic motives for giving. However, the research is shown to draw some potentially misleading conclusions and be unrepresentative of contingent valuation. Two recent economic studies using contingent valuation are then reported and shown to have identified non-economic motives for WTP. The complexity of value formation and expression is found to go far beyond that generally accepted by economic models. Greater consideration of the role played by attitudes and ethical considerations then becomes relevant to the interpretation of results being used in standard cost-benefit analysis and environmental policy. (shrink)

The purpose of this essay is to study the problem of inherent obscurity of the criterion for maximal utility in utilitarianism. For the sake of convenience of analysis, situations of moral actions are classified into four categories. It is shown that morality is flexible, especially in the positive sense, in that a virtuous action can be taken in various ways and/or to various degrees. For some situations it is inherently unclear what the moral requirement is, and whether it is a (...) maximum or a minimum. It is concluded that the schism of the principle of utility between the principle of the good and the principle of the right seems to be inevitable, and the interpretation of the ultimate criterion for maximal utility should be relaxed or interpreted separately and differently according to the situation of action. (shrink)

John Stuart Mill strongly supports capital punishment for aggravated murder. He rejects various arguments against capital punishment, including the claim that it is incompatible with respect for hu...

Sher's notion of deserved punishment has unacceptable implications. It does not justify punishing some serious wrongdoers, who are unwilling to commit lesser wrongs, more severely than minor offenders. It requires victim-inflicted punishments which repeat the wrongdoings, with the roles reversed. But if Sher moves away from such victim-inflicted punishments, then his theory should treat wrongdoers like tort-feasors who have to pay monetary compensations to their victims.