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)

This paper aims to lay bare the underlying logical structure of early Buddhist moral thinking. It argues that moral vocabulary in the Pali Suttas varies depending on the kind of agent under discussion and that this variance reflects an understanding that the phenomenology of moral experience also differs on the same basis. An attempt is made to spell this out in terms of attachment. The overall picture of Buddhist ethics that emerges is that of an agent-based moral contextualism. This account (...) does not imply that the prescription for moral conduct differs according to class of agent, but rather that the correct description of moral experience does. Further it implies that the descriptions of the moral experiences of different classes of agent differ phenomenologically, rather than in terms of overt behavioral characteristics. While most of the discussion is centered on the distinction between ordinary persons and disciples in higher training, the paper concludes with a brief exploration of the problematic moral experience of the arahat. (shrink)

The present article aims to explain Kamala??la’s understanding of the nature of insight, specifically considering it as the ‘discernment of reality’ -- a technical term identified with insight in the author’s well known Bh?van?krama? texts. I approach my analysis of bh?ta-pratyavek?? from three different angles. I begin by providing a rationale for its translation. This is followed by an account of Kamala??la’s reading of key passages in the La?k?vat?ra S?tra describing the process to which the term refers. Here the aim (...) is to illustrate Kamala??la’s understanding of bh?ta-pratyavek?? as it is actually experienced in meditation. The final section examines bh?ta-pratyavek?? in relation to other important technical terminology employed in the course of making arguments against his historical rival in debate, the Ch’an monk Mo ho yen. By providing these three different perspectives on the same process it is my hope that both scholars and practitioners will be able to more fully comprehend and benefit from the instructions provided by the ancient master Kamala??la. (shrink)

A close reading of the three Bhavanakramah texts, written by Kamalasila, reveals that their author was aware of two competing concepts of meditation prevalent in Tibet at the time of their composition. The two concepts of meditation,associated with the Sanskrit words bhavana and dhyana, can be related respectively to the Indian and Chinese sides of the well-known debates at bSam yas. The account of the Mahayana path outlined in these texts implies an acceptance of the precedence of bhavana over dhyana. (...) In this paper I argue that Kamalasila advocated bhavana – a conception of meditation which encompasses non-conceptual dhyana, but which also includes a discernment of reality that is conceptual in nature. Such conceptual discernment should not be understood simply as a process of ordinary rational understanding but rather as constituting a special kind of meditative wisdom. A failure to recognize the subtle differences between Kamalasila’s employment of the terms dhyana and bhavana, along with his advocacy of the latter, could easily lead to mistranslation and, with this, a basic misunderstanding of his position. In particular, it could lead to a conception of insight that is overly intellectual in nature. Given the historically important role that these texts played in the formation of Tibetan Buddhism, the implications of such a misconception could be far-reaching. This paper attempts to clarify the key meditation terminology found in the Bhavanakramas as well as demonstrate the rationale for using ‘meditation’ as the default translation for bhavana. (shrink)

What if a tree told a joke in the woods and there was no one there to hear it? Occasionally I watch The Ellen DeGeneres Show. I have appreciated Ellen as a comedian since she first came on the public scene, and one part of her talk show that I enjoy is the dancing in the opening segment, where Ellen dances to music played by a DJ, and she goes up into the audience and the overwhelmingly female audience dances (...) with her. I like to dance and I enjoy watching other people dance, but the Ellen dance segment also holds a special fascination for me, as there is a style of dancing I have observed over the last twenty-five years or so, a style that might as well be called “lesbian,” and which, if you don’t .. (shrink)

Scholars and environmentalists in the industrialized nations have repeatedly deplored the destruction of tropical forests as a byproduct of economic development. Their position is based upon scientific, economic, and ethical arguments. Proponents of economic development from the tropical nations recognize that its immediate benefits are enjoyed by their own relatively poor populations while the benefits of habitat preservation are enjoyed by the world as a whole. So far, few institutional mechanisms have been developed that can reconcile the competing perspectives. In (...) addition to reviewing the arguments in favor of and against habitat preservation, this paper proposes some innovative institutions that can both satisfy developmental aspirations and account for the global benefits of habitat preservation. (shrink)

Scholars and environmentalists in the industrialized nations have repeatedly deplored the destruction of tropical forests as a byproduct of economic development. Their position is based upon scientific, economic, and ethical arguments. Proponents of economic development from the tropical nations recognize that its immediate benefits are enjoyed by their own relatively poor populations while the benefits of habitat preservation are enjoyed by the world as a whole. So far, few institutional mechanisms have been developed that can reconcile the competing perspectives. In (...) addition to reviewing the arguments in favor of and against habitat preservation, this paper proposes some innovative institutions that can both satisfy developmental aspirations and account for the global benefits of habitat preservation. (shrink)

Fluctuating asymmetry (FA) is small deviations from perfect symmetry in normally bilaterally symmetrical traits. We examined the relationship between FA of five body traits (ear height, length of three digits, and ankle circumference) and self-reported scores of physical and verbal aggression in a sample of 90 boys aged 10 to 15 years. The relationships between FA and scores of aggression (particularly physical aggression) were found to be negative; in other words, the most symmetrical boys showed highest aggression. One trait (ankle (...) circumference) showed the characteristics of “ideal” FA—parametric mean of zero and a normal distribution. Mean asymmetries calculated from six repeated measures of ankle FA in 30 subjects taken over a period of five months showed strong negative associations with scores of physical aggression which were independent of age, height, and weight.It is argued that soft tissue “cyclical” FA (as opposed to “fixed” bony FA) is dependent on the secretion of hormones: for example, cortisol. Causal associations between behavioral traits such as aggresion and hormones will lead to similar correlations between FA and behavior. (shrink)

Like proper names, demonstratives, and definite descriptions, pronouns have referential uses. These can be 'essentially indexical' in the sense that they cannot be replaced by non-pronominal forms of reference. Here we show that the grammar of pronouns in such occurrences is systematically different from that of other referential expressions, in a way that illuminates the differences in reference in question. We specifically illustrate, in the domain of Romance clitics and pronouns, a hierarchy of referentiality, as related to the topology of (...) the grammatical phase. Our explanation is based on extending the 'Topological Mapping Hypotheses' of Longobardi and Sheehan & Hinzen. The extended topology covers the full range of interpretations, from purely predicative to quantificational, to referential and deictic. Along this scale, grammatical complexity increases, and none of these forms of reference is lexical. This provides evidence for the foundational conclusion that the source of essential indexicality is grammatical rather than lexical, semantic or pragmatic. (shrink)

Redish et al. trace vulnerabilities in habit and planning systems almost exclusively to pharmacological effects of addictive substances on underlying brain systems. As we discuss, however, these systems also can be disrupted by purely psychological factors inherent in normal decision-making and everyday behavior. A truly unified model must integrate the contribution of both sets of factors in driving addiction.

The present article aims to explain Kamala??la’s understanding of the nature of insight, specifically considering it as the ‘discernment of reality’ -- a technical term identified with insight in the author’s well known Bh?van?krama? texts. I approach my analysis of bh?ta-pratyavek?? from three different angles. I begin by providing a rationale for its translation. This is followed by an account of Kamala??la’s reading of key passages in the La?k?vat?ra S?tra describing the process to which the term refers. Here the aim (...) is to illustrate Kamala??la’s understanding of bh?ta-pratyavek?? as it is actually experienced in meditation. The final section examines bh?ta-pratyavek?? in relation to other important technical terminology employed in the course of making arguments against his historical rival in debate, the Ch’an monk Mo ho yen. By providing these three different perspectives on the same process it is my hope that both scholars and practitioners will be able to more fully comprehend and benefit from the instructions provided by the ancient master Kamala??la. (shrink)

I propose that a distinction can be drawn between two fundamental kinds of racism: own-race-present racism and own-race-absent racism. In own-racepresent racism, the race of the racist figures as a term in her racist thinking; in own-race-absent racism it does not. While own-race-present racism might conform readily to commonsense understandings of racism, own-race-absent racism less clearly does. I provide evidence that these two kinds are there to be identified and raise considerations regarding the benefits, both theoretical and practical, of adopting (...) the less-obvious concept of own-race-absent racism. (shrink)

The vast majority of research in nursing ethics over the last decade indicates that nurses may not be fully prepared to ‘deliver the good’ for their patients, or to contribute appropriately in the wider current health care climate. When suitable research projects were evaluated for this article, one key question emerged: if nurses are educationally better prepared than ever before to exercise their ethical decision-making skills, why does research still indicate that the expected practice-based improvements remain elusive? Hence, a number (...) of ideas gleaned from recent research about the current nature of nursing ethics, and especially teaching nursing ethics to student nurses, are analysed and critiqued in this article, which concludes with a cluster of ideas and conclusions based on that analysis. It is hoped that such a review may serve as a catalyst for nurse educators to re-examine their teaching practices with a view to enhancing good nursing practice through educational means. (shrink)

Background:Acting ethically, in accordance with professional and personal moral values, lies at the heart of nursing practice. However, contextual factors, or obstacles within the work environment, can constrain nurses in their ethical practice – hence the importance of the workplace ethical climate. Interest in nurse workplace ethical climates has snowballed in recent years because the ethical climate has emerged as a key variable in the experience of nurse moral distress. Significantly, this study appears to be the first of its kind (...) carried out in New Zealand.Aim/objective:The purpose of this study was to explore and describe how registered nurses working on a medical ward in a New Zealand hospital perceive their workplace ethical climate.Research design/participants/context:This was a small, qualitative descriptive study. Seven registered nurses were interviewed in two focus group meetings. An inductive method of thematic data analysis was used for this research.Ethical considerations:Ethics approval for this study was granted by the New Zealand Ministry of Health’s Central Regional Health and Disability Ethics Committee on 14 June 2012.Findings:The themes identified in the data centred on three dominant elements that – together – shaped the prevailing ethical climate: staffing levels, patient throughput and the attitude of some managers towards nursing staff.Discussion:While findings from this study regarding staffing levels and the power dynamics between nurses and managers support those from other ethical climate studies, of note is the impact of patient throughput on local nurses’ ethical practice. This issue has not been singled out as having a detrimental influence on ethical climates elsewhere.Conclusion:Moral distress is inevitable in an ethical climate where the organisation’s main priorities are perceived by nursing staff to be budget and patient throughput, rather than patient safety and care. (shrink)

This study investigated students’ perceptions following a prepared, common presentation regarding academic integrity provided by their residence dons. This peer instruction study utilized both quantitative and qualitative analyses of survey data within a pre-test post-test design. Overall, students reported gains in knowledge, as well as confidence in their knowledge of academic integrity. Notably, students reported increases in their personal value for academic integrity after participating in the presentations. Overall, the quality and content of the presentations were judged positively, and participants’ (...) ratings of the presentation were predictive of increases in personal value of academic integrity, as well as self-reported knowledge and confidence gains. Qualitative analyses supported that the key ideas in the presentation served as the focal material for discussion, but also introduced specific topics that students wanted to explore in greater depth. (shrink)

This paper continues a recent exchange in this journal concerning explanationist accounts of epistemic justification. In the first paper in this exchange, Byerly argues that explanationist views judge that certain beliefs about the future are unjustified when in fact they are justified. In the second paper, McCain defends a version of explanationism which he argues escapes Byerly’s criticism. Here we contribute to this exchange in two ways. In the first section, we argue that McCain’s defense of explanationism against Byerly’s objection (...) is unsuccessful. Then, in the second section, we develop an independent objection to explanationism from a different direction. If our arguments in each section are sound, then not only do explanationist accounts of epistemic justification judge beliefs that are justified to be unjustified, but they judge beliefs that are unjustified to be justified. Explanationism faces problems on both sides. (shrink)

Essays by various philosphers on the work of Tyler Burge and Burge's extensive responses.