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 purpose of this study is to examine the importance that real patients attach to their right to withdraw from an on-going feasibility randomised trial (RCT) evaluating types and timings of breast reconstruction (two parallel trials) following mastectomy for breast cancer. Our results show that, while some respondents appreciated that exercising the right to withdraw would defeat the scientific objective of the trial, some patients with a surgical preference consented only given the knowledge they could withdraw if they were not (...) allocated to their preferred treatment. (shrink)

Brexit activists demonstrating outside the British Houses of Parliament were studied in situ to examine their potential for pro-group extreme behavior. This involved activists of two polarized, opposing views; those of Leave and Remain. The research engaged concepts linking the different theoretical perspectives of identity fusion and personal construct psychology. The study measured participants' degree of fusion to their group using a verbal measure. Willingness to undertake extreme acts was assessed in several ways: a measure of willingness to fight for (...) the group, adaptations of the trolley dilemma and questions regarding political violence. Individual construing was examined using repertory grid technique and a semi-structured interview. Results were similar for both Leave and Remain participants. The majority of activists identified as “fused” to their group and, if so, were more likely to undertake hypothetical extreme behavior compared to those who did not identify as “fused.” Repertory grid technique indicated that becoming an activist provided individuals with a clearer and more positive view of themselves. Opposition activists were construed more negatively and extremely than fellow activists, and this construal was associated with an increased willingness to undertake extreme pro-group behavior. This was consistent with the personal construct model of radicalization and was heightened in those who were “fused.” Interview data provided support for the constructivist model and revealed characteristics and concerns of the two groups. Overall, the findings indicate that campaigning organizations contain fused individuals, who are more likely to undertake hypothetical pro-group violence including self-sacrifice. This has broader implications which may be particularly pertinent, given the violent impact of extremist activists around the globe. (shrink)

In A Climate of History Dipesh Chakrabarty locates Kant’s speculative reading of Genesis as “the Enduring Fable” furnishing the background for human domination and earthly destruction. Writing from the fable’s “ruins,” Chakrabarty urges the elaboration of new fables that provide the background ethics and meanings required to recast relations between humans and the natural world. Responding to Chakrabarty’s challenge, we outline two “fables” based first in the oft ignored Genesis 2, and second, in Matauranga Māori. Although marginalised, these extant fables (...) provide the imaginary for radically other ways of being human in a more-than-human world in turmoil. (shrink)

The idea of dignity is often taken to be a foundation for principles of justice and democracy. In the West it has numerous formulations and conceptualisations. Within the capabilities approach to justice theorists have expanded the concept of dignity to encompass animals and ecological communities. In this article I rework the idea of dignity to include the Māori philosophical concepts of Mauri, tapu and mana – something I argue is necessary if the capabilities approach is to decolonise in the Aotearoa (...) context. Furthermore, the article links the nation’s recognition of three extensive geographical regions – Te Awa Tupua, Te Urewera and Mt Taranaki – as legal persons to Mātauranga Māori and nonhuman dignity. In doing so, I identify the potential that this understanding of dignity and these legal moves have to decolonise democracy within the settler state. (shrink)

This chapter highlighted some salient trends in pediatric ethicsEthics, pediatric from different parts of the globe. It is interesting to note that although diverse, there are many similarities between ethical challenges in pediatrics in different parts of the world.

This article presents a case for thinking that moral principles within Aristotle's ethical theory can be both codifiable and action-guiding without minimizing the role of practical reason in determining what should be done. I argue that McDowell dismisses this possibility too hastily. Much of the force of this case rests on my interpretation of "for the most part" relationships in Aristotle.

Originally published in German, Christoph Wulf’s _Anthropology_ sets its sights on a topic as ambitious as its title suggests: anthropology itself. Arguing for an interdisciplinary and intercultural approach to anthropology that incorporates science, philosophy, history, and many other disciplines, Wulf examines—with breathtaking scope—all the ways that anthropology has been understood and practiced around the globe and through the years. Seeking a central way to understand anthropology in the midst of many different approaches to the discipline, Wulf concentrates on the human (...) body. An emblem of society, culture, and time, the body is also the result of many mimetic processes—the active acquisition of cultural knowledge. By examining the role of the body in the performance of rituals, gestures, language, and other forms of imagination, he offers a bold new look at how culture is produced, handed down, and transformed. Drawing such examinations into a comprehensive and sophisticated assessment of the discipline as a whole, _Anthropology_ looks squarely at the mystery of humankind and the ways we have attempted to understand it. (shrink)

Introduction Perhaps more than any other member of the Frankfurt School, Herbert Marcuse articulated a hope for a radically transfigured world. He imagined a world characterized by receptive, generous relationships rather than domination and violence. Yet Marcuse's philosophy of liberation has been placed on trial within various critical circles. Michel Foucault's rejection of the “repressive hypothesis” and his concomitant analysis of power as generative is typically interpreted as an indirect response to Marcuse's tendency to treat the social order as a (...) primarily repressive force vis-à-vis our instincts and desires.1 Martin Jay has expressed concerns about the…. (shrink)

The exogenous cycles and population dynamics of the community at Penrith, Cumbria, England, have been studied (1557-1812) using aggregative analysis, family reconstitution and time series analysis. This community was living under marginal conditions for the first 200 years and the evidence presented is of a homeostatic regime where famine, malnutrition and epidemic disease acted to regulate the balance between resources and population size. This provides an ideal historic population for an investigation of the direct and indirect effects of malnutrition. Throughout (...) the period studied, a short wavelength oscillation in grain prices was apparently the major external factor that drove exogenous cycles in mortality, birth rate, and migration. In particular, the different responses of children to variations in food supply are emphasised; fluctuations in poor nutrition correlated significantly with the variations in mortality rates for infants (probably indirectly during pregnancy and directly during the first year of life) and for young children (via susceptibility to lethal infectious diseases). Migratory movements contributed to the maintenance of homeostasis in the population dynamics. A medium wavelength cycle in low winter temperatures was associated with a rise in adult mortality which, in turn, promoted an influx of migrants into this saturated habitat. A model incorporating these interacting associations between vital events and exogenous cycles is presented: grain prices were an important density-dependent factor and constituted the major component of the negative feedback of this population and drove the exogenous, short wavelength mortality cycles. Cycles of births and immigration provide a positive feedback for the build-up of susceptibles and the initiation of smallpox epidemics and increased population size. (shrink)

This penultimate volume of Santayana's letters chronicles Santayana's life during a difficult time--the war years and the immediate postwar period. The advent of World War II left Santayana isolated in Rome, and the difficulties of wartime travel across borders forced him to abandon plans to move to more agreeable locations in Switzerland or Spain. During these years, Santayana lived in a single room in a nursing home run by the "Blue Sisters" of the Little Company of Mary in Rome, where, (...) during the winter months, he did much of his writing in bed in order to stay warm. And yet, despite wartime deprivations, illness, and old age, Santayana was remarkably productive, completing both his autobiography Persons and Places and The Idea of Christ in the Gospels: or God in Man, and all but completing Dominations and Powers. He confided to one correspondent that he had "never been more at peace or more happy."The eight books of The Letters of George Santayana bring together over 3,000 letters, many of which have been discovered in the fifty years since Santayana's death. Letters in Book Seven are written to such correspondents as his friend and protégée Daniel Cory, his financial manager and heir George Sturgis, and the American poet Robert Lowell. The correspondence with Lowell--which began when the younger writer sent Santayana a copy of his Pulitzer Prize-winning Lord Weary's Castle--signals an important new friendship, which became a source of affection and intellectual engagement in Santayana's final years. (shrink)

Mohanty, J.N. Understanding Husserl's transcendental phenomenology.--Fink, E. The problem of the phenomenology of Edmund Husserl. Operative concepts in Husserl's phenomenology.--Funke, G. A transcendental-phenomenological investigation concerning universal idealism, intentional analysis, and the genesis of habitus: archē, phansis, hexis, logos.--Pentzopoulou-Valalas, T. Reflections on the foundation of the relation between the a priori and the eidos in the phenomenology of Husserl.--Landgrebe, L. Regions of being and regional ontologies in Husserl's phenomenology. The problem posed by the transcendental science of the a priori of the (...) life world.--Wahl, J. Notes on the first part of Experience and judgment by Husserl.--Landgrebe, L. A letter from Ludwig Landgrebe to Jean Wahl.-- Wahl, J. A note on some empiricist aspects of the thought of Husserl.--Toulemont, R. The specific character of the social according to Husserl. (shrink)

Introduction -- Tending the dark fire: the Boehmian notion of drive -- The night-side of nature: the early Schellingian unconscious -- The speculative psychology of dissociation: the later Schellingian unconscious -- Schellingian libido theory.

There is as yet no general agreement about exactly when Locke's Second Treatise of Government was written. Primarily as a result of Peter Laslett's arguments, the old assumption that it was written after the Revolution of 1688 has been abandoned, and it is almost universally agreed that both of the Two Treatises were written (apart from a small number of additions made in 1689) in the period between Locke's return to England from France at the end of April 1679 and (...) his departure for Holland in August 1683. An earliest possible date for the First Treatise can be established without difficulty. It cannot have been started before Filmer's Patriarcha was published in the winter of 1679-80, and probably not before Locke bought his own copy on 22 January 1680. Theories about the composition of the Second Treatise may therefore be divided into two classes: those which suppose, with Laslett, that it was begun in 1679, before Patriarcha was published, and therefore before Locke could have formed any intention of writing the First Treatise; and those which hold that it was not started until Locke had written at least the main part of the First. The second is of course the traditional view, and one that was taken for granted before Laslett's work; its most notable defender has been Richard Ashcraft, who has accepted Laslett's demolition of the 1689 dating, but has diverged from him in ascribing the Second Treatise to the period after the dissolution of the Oxford Parliament in March 1681. Ashcraft's criticisms of Laslett have been accepted by several recent writers, notably David Wootton, Mark Goldie and John Marshall, but they themselves have not agreed with each other or with Ashcraft in their positive claims. The whole question is therefore worth examining again. (shrink)

In his Meditations Descartes tells us that he initially thought error might be avoided if he withheld assent “no less carefully from what is not plainly certain and indubitable than from what is obviously false.” For example, he thinks it plainly certain and indubitable that he is “sitting by the fire, wearing a winter cloak, holding this paper in my hands, and so on.” And yet even what is “plainly certain and indubitable” can be doubted. “I will suppose, then, not (...) that there is a supremely good God, the source of truth; but that there is an evil spirit, who is supremely powerful and intelligent, and does his utmost to deceive me.” Such a deceiver can spin illusions that appear indubitably real and true—of hands, fire, cloak, paper—and not only when there are none present in any particular case but even where there are none at all in any case. “I will suppose that sky, air, earth, colors, shapes, sounds and all external objects are mere delusive dreams, by means of which he lays snares for my credulity.”2 The deceiver hypothesis is the most difficult skeptical doubt Descartes must surmount in the remaining Meditations. I say the deceiver hypothesis, and for Descartes the deceiver is a mere possibility, raised so as to motivate the reconstitution of knowledge that follows. That there might be a powerful deceiver is itself a threat to knowledge for Descartes. Indeed even the possibility of an evil deceiver is so powerful a threat that Descartes must do nothing less than prove God’s existence to reestablish certainty. It is only at the end of his Meditations that Descartes can say, as if looking back on a hysterical moment, that the evil deceiver idea was “exaggerated” and “ridiculous.”3.. (shrink)

In the academic year 1920-1921 at the University of Freiburg, Martin Heidegger gave a series of extraordinary lectures on the phenomenological significance of the religious thought of St. Paul and St. Augustine. The publication of these lectures in 1995 settled a long disputed question, the decisive role played by Christian theology in the development of Heidegger’s philosophy. The lectures present a special challenge to readers of Heidegger and theology alike. Experimenting with language and drawing upon a wide range of now (...) obscure authors, Heidegger is finding his way to Being and Time through the labyrinth of his Catholic past and his increasing fascination with Protestant theology. A Companion to Heidegger's Phenomenology of Religious Life is written by an international team of Heidegger specialists. (shrink)

This paper considers Cassius Dio's account of the early worship of Augustus. Its main focus is the number of cults consecrated to the worship of Rome's new undisputed leader and his father, the now deceased and deified Divus Iulius, after the triumvir, on his way back from Alexandria in 29 b.c.e., wintered in Asia Minor. In his account of how the first official worship of Augustus was organized, Dio describes how Augustus let two separate cults inaugurate: a joint cult to (...) the worship of Divus Iulius and the goddess Thea Roma—a Greek deity, which since the second century served as a personification of Roman rule or Roman power—and a personal cult to the worship of the victorious triumvir. (shrink)

Temporality underpins how living systems coordinate and function. Unlike measures that use mathematical conventions, lived temporalities grant functional cohesion to organisms-in-the-world. In foxtail grasses, for example, self-maintenance meshes endogenous processes with exogenous rhythms. In embrained animals, temporalities can contribute to learning. And cowbirds coordinate in a soundscape that includes conspecifics: social learning allows them to connect copulating with past events such that females exert ‘long-distance’ control over male singing. Using Howard Pattee’s work, we compare the foxtail’s self-maintenance, gender-based cowbird learning (...) and how humans manage multi-scalar activity. We argue that, while all living things coordinate, temporal ranging is typical of vertebrates. As primates, humans too use temporal ranging – they can draw on social learning, anticipate winter and manage coordinated action. However language behaviour grants new control over the scales of time. People connect the impersonal to lived experience in narratives, as they draw on autobiography and enact cultural practices. Humans become singular individuals who use temporal experience to manage affect, relationships, beliefs, fictions, and knowledge. Individual subjectivity permits collaborative and competitive activity based on linking events with quite different histories. As a result, alone of the vertebrates, we claim that humans become time-rangers. (shrink)

I argue that, when Alcibiades' encomium to Socrates is interpreted in light of Socrates' presentation of Diotima's speech, which immediately proceeds it, it shows Socrates to be at the top level of Diotima's "ladder of ascent" to Beauty. If Alcibiades is correct, Socrates' pretense of ignorance is an ironic sham. Socrates, as Plato's mystagogos, must have experiential knowledge of the Form of Beauty.

Volume 35 contains papers and commentaries presented to the Boston Area Colloquium in Ancient Philosophy during academic year 2018-19. Works: Commentary on _De Anima_ (author), Nicomachean Ethics (moderation). Topics: Humean motivation, memory-oblivion & myth, final causality and ontology of life.

Volume 36 contains papers and commentaries presented to the Boston Area Colloquium in Ancient Philosophy during academic year 2019-20. Works: _Republic 7, Topics 1.2, Nicomachean Ethics 3.5, Isis and Osiris_. Topics: types of dialectic, political philosophy, voluntary, hermeneutical retrieval, (un)wanted emotions.

Volume 37 contains papers and commentaries presented to the Boston Area Colloquium in Ancient Philosophy during 2022. Works: _Phaedo_, _Statesman_, _De Caelo_, _Metaphysics N_, _Enneads_. Topics: immortality, Forms; dialectic, myth, law; elements, inclination, place; mathematics and explanation; mystical union.

In late winter of 1864, Charles Darwin received two folio volumes on radiolarians, a group of one-celled marine organisms that secreted siliceous skeletons of unusual geometry. The author, the young German biologist Ernst Haeckel (fig. 1), had himself drawn the figures for the extraordinary copper-etched illustrations that filled the second volume.1 The gothic beauty of the plates astonished Darwin (fig. 2 ), but he must also have been drawn to passages that applied his theory to construct the descent relations of (...) these little known creatures. He replied to Haeckel that the volumes "were the most magnificent works which I have ever seen, & I am proud to possess a copy from the author."2 Emboldened by his own initiative in contacting the famous naturalist, Haeckel, a few days later, sent Darwin a newspaper clipping that described a meeting of the Society of German Naturalists and Physicians at Stettin, which occurred during the previous autumn. The article gave an extended and laudatory account of Haeckel's lecture defending Darwin's theory.3 Darwin immediately replied in his second letter: "I.. (shrink)

In this paper, we argue that our moral concern for future well-being should reduce over time due to important practical considerations about how humans interact with spacetime. After surveying several of these considerations (around equality, special duties, existential contingency, and overlapping moral concern) we develop a set of core principles that can both explain their moral significance and highlight why this is inherently bound up with our relationship with spacetime. These relate to the equitable distribution of (1) moral concern in (...) a universe that we can only causally affect in one temporal direction; (2) access to the benefits from using spacetime as a resource; and (3) the burdens of care given (1) and (2). We conclude by considering the practical implications of our argument and find that, while it is often assumed that a preference for present over future well-being weakens the case for existential risk mitigation, this likely is not the case. (shrink)

‘Water is H2O’ is one of the most frequently cited sentences in analytic philosophy, thanks to the seminal work of Saul Kripke and Hilary Putnam in the 1970s on the semantics of natural kind terms. Both of these philosophers owe an intellectual debt to the empiricist metaphysics of John Locke's Essay Concerning Human Understanding, while disagreeing profoundly with Locke about the reality of natural kinds. Locke employs an intriguing example involving water to support his view that kinds (or ‘species’), such (...) as water and gold, are the workmanship of the human mind. This is the point of his story about a winter visitor to England from Jamaica, who is astonished to find that the water in his basin has turned solid overnight, and proceeds to call it ‘hardened water’. Locke criticizes this judgement, maintaining that it is more consonant with common sense to regard water and ice as different kinds of substance. Putnam, by implication, disagrees. Deploying his imaginary example of Twin Earth—a distant planet where a watery-looking substance, XYZ, rather than H2O, fills the oceans and rivers—he maintains that common sense supports the judgement that XYZ and H2O, despite their superficial similarity, are not the same kind of substance, precisely because their molecular compositions are different. Here it will be argued that both views are mistaken, but that, in this dispute, Locke has more right on his side than his modern opponents do. (shrink)

This study of three central themes in the logic of Alexander of Aphrodisias, the greatest of the ancient Aristotelian commentators, provides insight not only into Aristotle's logical writings but also into the tradition of scholarship which they spawned.

In _Jesuit Superior General Luis Martín García and His Memorias_, David Schultenover presents an account and interpretation of Martín’s memoir covering most of his sixty years, including candid reflections on church-state events and his personal life.

Volume 35 contains papers and commentaries presented to the Boston Area Colloquium in Ancient Philosophy during academic year 2018-19. Works: Commentary on _De Anima_, Nicomachean Ethics. Topics: Humean motivation, memory-oblivion & myth, final causality and ontology of life.

Volume 36 contains papers and commentaries presented to the Boston Area Colloquium in Ancient Philosophy during academic year 2019-20. Works: _Republic 7, Topics 1.2, Nicomachean Ethics 3.5, Isis and Osiris_. Topics: types of dialectic, political philosophy, voluntary, hermeneutical retrieval, wanted emotions.

Volume 36 contains papers and commentaries presented to the Boston Area Colloquium in Ancient Philosophy during academic year 2019-20. Works: _Republic 7, Topics 1.2, Nicomachean Ethics 3.5, Isis and Osiris_. Topics: types of dialectic, political philosophy, voluntary, hermeneutical retrieval, wanted emotions.