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)

Do cultural models facilitate particular ways of perceiving interactions in nature? We explore variability in folkecological principles of reasoning about interspecies interactions. In two studies, Indigenous Panamanian Ngöbe and U.S. participants interpreted an illustrated, wordless nonfiction book about the hunting relationship between a coyote and badger. Across both studies, the majority of Ngöbe interpreted the hunting relationship as cooperative and the majority of U.S. participants as competitive. Study 2 showed that this pattern may reflect different beliefs about, and perhaps different (...) awareness of, plausible interspecies interactions. Further probes suggest that these models of ecological interaction correlate with recognition of social agency in nonhuman animals. We interpret our results in terms of cultural models of nature and nonhuman agency. (shrink)

Theory‐of‐mind (ToM) is an integral part of social cognition, but how it develops remains a critical question. There is evidence that children can gain insight into ToM through experience, including language training and explanatory interactions. But this still leaves open the question of how children gain these insights—what processes drive this learning? We propose that analogical comparison is a key mechanism in the development of ToM. In Experiment 1, children were shown true‐ and false‐belief scenarios and prompted to engage in (...) multiple comparisons (e.g., belief vs. world). In Experiments 2a, 2b, and 3, children saw a series of true‐ and false‐belief events, varying in order and in their alignability. Across these experiments, we found that providing support for comparing true‐ and false‐belief scenarios led to increased performance on false‐belief tests. These findings show that analogical comparison can support ToM learning. (shrink)

In January 2023, the Science and Security Board of the Bulletin of the Atomic Scientists moved the hands of the Doomsday Clock forward to 90 s before midnight.

> Wealthy nations must do much more, much faster. The United Nations General Assembly in September 2021 will bring countries together at a critical time for marshalling collective action to tackle the global environmental crisis. They will meet again at the biodiversity summit in Kunming, China, and the climate conference 26) in Glasgow, UK. Ahead of these pivotal meetings, we—the editors of health journals worldwide—call for urgent action to keep average global temperature increases below 1.5°C, halt the destruction of nature (...) and protect health. Health is already being harmed by global temperature increases and the destruction of the natural world, a state of affairs health professionals have been bringing attention to for decades.1 The science is unequivocal; a global increase of 1.5°C above the preindustrial average and the continued loss of biodiversity risk catastrophic harm to health that will be impossible to reverse.2 3 Despite the world’s necessary preoccupation with COVID-19, we cannot wait for the pandemic to pass to rapidly reduce emissions. Reflecting the severity of the moment, this editorial appears in health journals across the world. We are united in recognising that only fundamental and equitable changes to societies will reverse our current trajectory. The risks to health of increases above 1.5°C are now well established.2 Indeed, no temperature rise is ‘safe’. In the past 20 years, heat-related mortality among people aged over 65 has increased by more than 50%.4 Higher temperatures have brought increased dehydration and renal function loss, dermatological malignancies, tropical infections, adverse mental health outcomes, pregnancy complications, allergies, and cardiovascular and pulmonary morbidity and mortality.5 6 Harms disproportionately affect the most vulnerable, including children, older populations, ethnic minorities, poorer communities and those with underlying health problems.2 4 Global heating is also contributing to the decline in …. (shrink)

This commentary addresses public health issues underlying homelessness and related law, policy, and advocacy options. After framing public health issues for affected individuals and the community, legal and policy approaches and related barriers are assessed. Major topics include deficits in housing availability, the role of state-based Medicaid programs, criminalization of homelessness, and the use of emergency declarations seeking to address particular issues related to homelessness in select states and localities.

Intuitionistic logic is presented here as part of familiar classical logic which allows mechanical extraction of programs from proofs. to make the material more accessible, basic techniques are presented first for propositional logic; Part II contains extensions to predicate logic. This material provides an introduction and a safe background for reading research literature in logic and computer science as well as advanced monographs. Readers are assumed to be familiar with basic notions of first order logic. One device for making this (...) book short was inventing new proofs of several theorems. The presentation is based on natural deduction. The topics include programming interpretation of intuitionistic logic by simply typed lambda-calculus (Curry-Howard isomorphism), negative translation of classical into intuitionistic logic, normalization of natural deductions, applications to category theory, Kripke models, algebraic and topological semantics, proof-search methods, interpolation theorem. The text developed from materal for several courses taught at Stanford University in 1992-1999. (shrink)

In the book, basic principles of syncretic logic (sycretics) are expounded upon, with the help of which group relationships of a philosophical nature are treated. Classical philosophical laws are analyzed, new assertions are formulated, laying claim to the position of laws. Syncretic logic is used for constructing the axiomatic theory of carriers and the analysis of its consequences. The problem of the origins of life is considered, the connection between the course of existence and the laws of conservation in physics (...) is expounded upon, the universal scheme of logical operations is described, the components of the structure of a world view are specified. The work is intended for a wide circle of individuals with philosophical and general scientific interests. (shrink)

Ancient allures the postmodern social subject trapped in the strangeness of time—the time after the end of history. For that time-beaten subject ancient is the unconscious of coherence, predictability, and certainty. Or perhaps that ancient is a glory fled. Whatsoever, ancient is generally sacralized—irrespective of the type of socialization that happened in the past—and journey to the ancient is often deemed to be a pilgrimage. When ideas of the ancient in their individuality and totality inter alia become the natural intellectual (...) resource for rebuilding postmodern societies, discriminative ingenuity becomes an essential faculty. Any uncritical reverence of the ancient becomes antithetical to modern social and political values, inviting the risk of reproducing inequities of the past. This article problematizes such uncritical dependence on the ancient using Ancient Indian Jurisprudence, which has been looked up on as a repository of moral and legal values, as a case in point. It meditates from the experiences and perspectives of an imaginary ‘teaching subject’ on the many pitfalls and possibilities of the ancient as it builds a framework of teaching and learning, and a representative scheme of evaluation for Ancient Indian Jurisprudence. (shrink)

The Irish poet W. B. Yeats once wrote, with great sapience and perception: Nor dread, nor hope attend A dying animal; A man awaits his end Dreading and hoping all. That death has ever been a problem to man is attested as far back as we can trace our species in the archaeological record—indeed, it seems to have been a problem even for that immediate precursor of homo sapiens, the so-called Neanderthal Man; for he buried his dead.

In lieu of an abstract, here is a brief excerpt of the content:FEYERABEND'S EPISTEMOLOGY AND BRECHTS THEORY OF THE DRAMA by S. G. Couvalis In his early paper, "On the Improvement of the Sciences and the Arts," Feyerabend argues that, just as rival hypotheses show the shortcomings of entrenched scientific hypotheses, so theatre which presents hypotheses contrary to common beliefs about human beings shows the shortcomings of these beliefs. It develops understanding of human relations more effectively than intellectual debate because (...) it is a more complex medium whose elements can "represent the contrary hypotheses at the same time."1 He takes Brecht to be the first theorist of such a theatre. I shall argue that Brecht's epistemology is similar to Feyerabend's early epistemology and that his dramatic theory is a consequence of it.2 1 shall also argue, however, that Feyerabend is wrong in saying that Brechtian theatre presents contrary hypotheses at the same time, because plays, like descriptions, are theory-laden and Brecht, in any case, intends to show on stage that tragedies have social origins and not to present contrary hypotheses about human beings. According to Brecht, most people improperly assume that human behavior and social relations follow fixed patterns inherent in nature because they have been unable to compare the human behavior they know with that in other societies. They take what they experience to be typically human. Moreover, they interpret their social world as they have been taught: "A child, living in a world of old men... knows the run of things before he can walk."3 Feyerabend brings out the effect of such training very vividly: "The teaching procedures both shape the 'appearance,' or 'phenomenon' and establish a firm connection with words, so that finally the phenomena seem to speak for themselves...."4 Because these interpretations of the social world which children are taught are descriptive, explanatory, and prescriptive, they are more 117 118Philosophy and Literature complex and more dangerous than the interpretations of physical objects they are taught. For example, children learn different evaluations of precisely the same behavior in males and females through being taught how to describe it. In being taught to describe certain behavior as "manly" they are taught both that it arises from a male's nature and that it is laudable behavior for boys but not for girls. "Manly" behavior in a woman is not "confident" or "forthright," but "aggressive" or "pushy." In order to stop us from regarding traditional behavior patterns and social relations as unchangeable, and to enable us to question our descriptions of them, Brecht argues that the dramatist must cause us to cease to regard such patterns and social relations as familiar givens that can only be described in one way. To achieve this, he must not structure his plays on the Aristotelian model. The Aristotelian model makes audiences incapable of criticizing the dramatic message, imparts the view that the sources of tragedy lie in an inexplicable human essence, and presents social rules as if they were unquestionable natural laws. Instead, he should structure his plays to induce in audiences a scientific attitude to social relations and patterns of behavior. Like Feyerabend, Brecht realizes that a scientific attitude is not displayed by collecting descriptions of experience without considering whether the interpretations contained in the descriptions are correct. In Galileo, his view of those who mechanically describe experience in traditional terms is shown in Galileo's replies to the Aristotelian arguments of Andrea. When Andrea argues, "I can see that the sun's not in the same place in the evening and morning. So it can't stand still. It just can't," Galileo replies, "You 'W! What do you see? You see nothing at all. You're just gaping. Gaping isn't seeing." He then demonstrates to Andrea that the apparent motions of objects need not be their real motions because an apparent motion can be caused in more than one way. 5 Brecht shows that the central question for the scientist is not "How shall I collect descriptions of appearances?" but "What is it that I really perceive and how is it caused?" He argues elsewhere that "there's a vast difference between experiment and experience" because experiments are set up to test... (shrink)