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)

In this consensus report by a diverse group of academics who conduct and/or are concerned about social and behavioral genomics (SBG) research, the authors recount the often‐ugly history of scientific attempts to understand the genetic contributions to human behaviors and social outcomes. They then describe what the current science—including genomewide association studies and polygenic indexes—can and cannot tell us, as well as its risks and potential benefits. They conclude with a discussion of responsible behavior in the context of SBG research. (...) SBG research that compares individuals within a group according to a “sensitive” phenotype requires extra attention to responsible conduct and to responsible communication about the research and its findings. SBG research (1) on sensitive phenotypes that (2) compares two or more groups defined by (a) race, (b) ethnicity, or (c) genetic ancestry (where genetic ancestry could easily be misunderstood as race or ethnicity) requires a compelling justification to be conducted, funded, or published. All authors agree that this justification at least requires a convincing argument that a study's design could yield scientifically valid results; some authors would additionally require the study to have a socially favorable risk‐benefit profile. (shrink)

With the aim of studying foundations for self-other relations and understanding, we conducted an experimental investigation of a specific aspect of imitation in children with autism: the propensity to copy self-other orientation. We hypothesised that children with autism would show limitations inidentifying withthe stance of another person. We tested 16 children with autism and 16 non-autistic children with learning difficulties, matched on both chronological and verbal mental age, for their propensity to imitate the self- or other-orientated aspects of another person’s (...) actions. All participants were attentive to the demonstrator and copied her actions, but the children with autism were significantly less likely to imitate those aspects of her actions that involved movement in relation to her own vis-à-vis the child’s body. There were a number of children with autism who copied the identical geometric orientation of objects acted-upon. These results suggest that children with autism have a diminished propensity to identify with other people, and point to the importance of this mechanism for shaping self-other relations and flexible thinking. (shrink)

With the aim of studying foundations for self-other relations and understanding, we conducted an experimental investigation of a specific aspect of imitation in children with autism: the propensity to copy self-other orientation. We hypothesised that children with autism would show limitations inidentifying withthe stance of another person. We tested 16 children with autism and 16 non-autistic children with learning difficulties, matched on both chronological and verbal mental age, for their propensity to imitate the self- or other-orientated aspects of another person’s (...) actions. All participants were attentive to the demonstrator and copied her actions, but the children with autism were significantly less likely to imitate those aspects of her actions that involved movement in relation to her own vis-à-vis the child’s body. There were a number of children with autism who copied the identical geometric orientation of objects acted-upon. These results suggest that children with autism have a diminished propensity to identify with other people, and point to the importance of this mechanism for shaping self-other relations and flexible thinking. (shrink)

With the aim of studying foundations for self-other relations and understanding, we conducted an experimental investigation of a specific aspect of imitation in children with autism: the propensity to copy self-other orientation. We hypothesised that children with autism would show limitations in identifying with the stance of another person. We tested 16 children with autism and 16 non-autistic children with learning difficulties, matched on both chronological and verbal mental age, for their propensity to imitate the self- or other-orientated aspects of (...) another person’s actions. All participants were attentive to the demonstrator and copied her actions, but the children with autism were significantly less likely to imitate those aspects of her actions that involved movement in relation to her own vis-à-vis the child’s body. There were a number of children with autism who copied the identical geometric orientation of objects acted-upon. These results suggest that children with autism have a diminished propensity to identify with other people, and point to the importance of this mechanism for shaping self-other relations and flexible thinking. (shrink)

Comenius (1592 - 1670) war ein großer Europäer, ein kreativer Metaphysiker und überzeugter, aber nicht indoktrinierender Theologe, ein Pädagoge, der zugleich ein begnadeter Praktiker war, ein Politiktheoretiker, ein Literat und Linguist auf hohem Niveau. Der Wunsch, Gewalt von den Dingen fernzuhalten, stammt von ihm. Er wird verständlich, wenn man sich klar macht, dass Comenius „pansophisch“ (allumfassend) gedacht hat: Die Gewalt gegen die Dinge spiegelt die Gewalt gegen die Menschen, und beides muss aufhören. Die vorliegende Publikation zeigt eine fremde Welt, die (...) doch in unserer Zeit angesichts der Globalisierung aller Lebensbereiche wieder von großer Aktualität ist. Comenius fostered pansophic, all-encompassing thinking in philosophy, theology, history, politics and education. That is why today, in an age of increased globalisation, his works are the subject of renewed interest. Twenty-nine authors from eight countries, dedicated to this task, develop the picture of a great European thinker. (shrink)

This book is a collection of secondary essays on America's most important philosophic thinkers—statesmen, judges, writers, educators, and activists—from the colonial period to the present. Each essay is a comprehensive introduction to the thought of a noted American on the fundamental meaning of the American regime.

Adaptive immunity provides the unique ability to respond to a nearly infinite range of antigenic determinants. Given the inherent plasticity of the adaptive immune system, a series of tolerance mechanisms exist to reduce reactivity toward self. While this reduces the probability of autoimmunity, it also creates an important gap in adaptive immunity: the ability to recognize microbes that look like self. As a variety of microbes decorate themselves in self‐like carbohydrate antigens and tolerance reduces the ability of adaptive immunity to (...) react with self‐like structures, protection against molecular mimicry likely resides within the innate arm of immunity. In this review, we will explore the potential consequences of microbial molecular mimicry, including factors within innate immunity that appear to specifically target microbes expressing self‐like antigens, and therefore provide protection against molecular mimicry. (shrink)

A 'Kripke-style' semantics is given for combinatory logic using frames with a ternary accessibility relation, much as in the Tourley-Meyer semantics for relevance logic. We prove by algebraic means a completeness theorem for combinatory logic, by proving a representation theorem for 'combinatory posets.' A philosophical interpretation is given of the models, showing that an element of a combinatory poset can be understood simultaneously as a set of states and as a set of actions on states. This double interpretation allows (...) for one such element to be applied to another . Application turns out to be modeled the same way as 'fusion' in relevance logic.We also introduce 'dual combinators' that apply from the right. We then explore relationships to some well-known substructural logics, showing that each can be embedded into the structurally free. non-associative Lambek calculus, with the embedding taking a theorem ω to a statement of the form Γ ⊨ ω, where Γ is some fusion of the combinators needed to justify the structural assumptions of the given substructural logic. This builds on earlier ideas from Belnap and Meyer about a Gentzen system wherein structural rules are replaced with rules for introducing combinators. We develop such a system and prove a cut theorem. (shrink)

This paper formalizes part of a well-known psychological model of emotions. In particular, the logical structure underlying the conditions that trigger emotions are studied and then hierarchically organized. The insights gained therefrom are used to guide a formalization of emotion triggers, which proceeds in three stages. The first stage captures the conditions that trigger emotions in a semiformal way, i.e., without committing to an underlying formalism and semantics. The second stage captures the main psychological notions used in the emotion model (...) in dynamic doxastic logic. The third stage introduces a BDI-based framework (belief–desire–intention) with achievement goals, which is used to firmly ground the preceding stages. The result is a formalization of emotion triggers for BDI agents with achievement goals. The idea of proceeding in these stages is to provide different levels of commitment to formalisms, so that it remains relatively easy to extend or replace the used formalisms without having to start from scratch. Finally, we show that the formalization renders properties of emotions that are in line with the psychological model on which it is based. (shrink)

Late in 1990, the Center for the Study of Ethics in the Professions at Illinois Institute of Technology (lIT) received a grant of more than $200,000 from the National Science Foundation to try a campus-wide approach to integrating professional ethics into its technical curriculum.! Enough has now been accomplished to draw some tentative conclusions. I am the grant's principal investigator. In this paper, I shall describe what we at lIT did, what we learned, and what others, especially philosophers, can learn (...) from us. We set out to develop an approach that others could profitably adopt. I believe that we succeeded. (shrink)

Access to abortion services in the United States continues to decline. It does so not because of significant changes in legislation or court rulings but because fewer and fewer physicians wish to perform abortions and because most states now have "conscientious objection" legislation that makes it easy for physicians to refuse to do so. We argue in this paper that physicians have an obligation to perform all socially sanctioned medical services, including abortions, and thus that the burden of justification lies (...) upon those who wish to be excused from that obligation. That is, such persons should have to show how requiring them to perform abortions would represent a serious threat to their fundamental moral or religious beliefs. We use current California law as an example of legislation that does not take physicians' obligations into account and thus allows them too easily to declare conscientious objection. (shrink)

We present a solution to the paradox of free choice permission by introducing strong and weak permission in a deontic logic of action. It is shown how counterintuitive consequences of strong permission can be avoided by limiting the contexts in which an action can be performed. This is done by introducing the only operator, which allows us to say that only is performed (and nothing else), and by introducing contextual interpretation of action terms.

Bullot & Reber (B&R) provide compelling evidence that sensitivity to context, history, and design stance are crucial to theories of art appreciation. We ask how these ideas relate to broader aspects of human cognition. Further open questions concern how psychological essentialism contributes to art appreciation and how essentialism regarding created artifacts (such as art) differs from essentialism in other domains.

Due to natural selection pressure, certain aspects of memory may have been selected to give humans a survival advantage. Research has demonstrated that processing information for survival relevance leads to better item memory (i.e., the content of information) compared to control conditions. The current study investigates the effects of survival processing on context memory (i.e., memory for peripheral episodic details) and item memory to better understand when the survival processing memory advantage emerges. In this study, participants viewed objects in either (...) a plausible color, for example a red apple, or in an implausible color, such as a green pie. We chose this color plausibility manipulation because color is a detail that conveys information about the fitness of an item. After studying items in either a survival or moving (control) condition, participants made item memory judgments (did you see this item before?), and two context memory judgments: color context (in which color did you see this item?), and source context (in which condition did you see this item?). Results indicated better item memory for materials processed in the survival relative to moving condition. Critically, for color context there was a condition by plausibility interaction, where memory was best for plausibly colored items in the survival processing condition. There was no difference, however, in source context memory between the survival and moving conditions. These results suggest the survival processing memory advantage extends to some contextual details, but only those details that tap into the survival utility of items, such as color. (shrink)

As the implementation of new approaches and procedures of medical ethics is as complex and resource-consuming as in other fields, strategies and activities must be carefully planned to use the available means and funds responsibly. Which facilitators and barriers influence the implementation of a medical ethics decision-making model in daily routine? Up to now, there has been little examination of these factors in this field. A medical ethics decision-making model called METAP was introduced on three intensive care units and two (...) geriatric wards. An evaluation study was performed from 7 months after deployment of the project until two and a half years. Quantitative and qualitative methods including a questionnaire, semi-structured face-to-face and group-interviews were used. Sixty-three participants from different professional groups took part in 33 face-to-face and 9 group interviews, and 122 questionnaires could be analysed. The facilitating factors most frequently mentioned were: acceptance and presence of the model, support given by the medical and nursing management, an existing or developing ethics culture, perception of a need for a medical ethics decision-making model, and engaged staff members. Lack of presence and acceptance, insufficient time resources and staff, poor inter-professional collaboration, absence of ethical competence, and not recognizing ethical problems were identified as inhibiting the implementation of the METAP model. However, the results of the questionnaire as well as of explicit inquiry showed that the respondents stated to have had enough time and staff available to use METAP if necessary. Facilitators and barriers of the implementation of a medical ethics decision-making model are quite similar to that of medical guidelines. The planning for implementing an ethics model or guideline can, therefore, benefit from the extensive literature and experience concerning the implementation of medical guidelines. Lack of time and staff can be overcome when people are convinced that the benefits justify the effort. (shrink)

This is a complete exposition of a tight version of a fundamental theorem of computational complexity due to Levin: The inherent space complexity of any partial function is very accurately specifiable in a Π1 way, and every such specification that is even Σ2 does characterize the complexity of some partial function, even one that assumes only the values 0 and 1.

Currently there are persistent doubts about the meaning and contributions of the gene concept, mostly related to its interpretation as a stretch of DNA encoding a single functional product, i.e., the classical molecular gene concept. There is, however, much conceptual variation around genes, leading to important difficulties in genetics teaching. We investigated whether and how conceptual variation related to the gene concept and gene function models is present in school science and what potential problems it may bring to genetics teaching (...) and learning. Here, we report results on how ideas about genes and gene function are treated in textbooks and appear in students’ views and, also, about a teaching strategy for improving higher education students’ understanding of scientific models and conceptual variation around genes and their functions. (shrink)

A useful logic in which to specify normative system behaviour, deontic logic has a broad spectrum of possible applications within the field: from legal expert systems to natural language processing, database integrity to electronic contracting and the specification of fault-tolerant software.

Curriculum programmes are conventionally expected to produce outcomes or specific results demonstrated in the performance of learners. Usually the intended outcomes are expressed in the conceptual framework or design of the curriculum. Programme assessment is intended to collect data that will provide evidence for these effects on learners.

Trust has been identified as an indicator within Social Quality theory. As an important component of social quality, trust has become increasingly important in modern society because literature suggests that trust in a number of democratic countries is declining. Modern technologies and specialties are often beyond the understanding of lay individuals and thus, the need for trusting relations between lay individuals and organizations/individuals has grown. The purpose of the study was to examine the extent to which Australians (dis)trust individuals and (...) organizations/institutions. A national postal survey was conducted with 1,044 respondents recruited using the electronic white pages directory. Findings from multivariate analyses suggest that income, age, sex, and health status are associated with trust in groups of individuals and trust in organizations/institutions. The findings highlight populations where trust needs to be (re)built. Future government policy and practice should utilize these findings as a means of facilitating social quality. (shrink)

This essay briefly describes a few of the problems associated with using personhood language to defend the right to life of the pre‐implantation embryo. Arguing that an immaterial soul explains the personal identity of an embryo is problematic for many people because there is no apparent spiritual activity in the unborn. While some scholars argue that the embryo has the potential to act as an adult person and thus should be protected from harm, others contend that potentiality alone is insufficient (...) reason to ascribe special moral worth to the embryo in utero. For Thomas Aquinas, the soul is not only the life‐principle that organizes the human body, but it is also that by which the human being thinks and wills. By making suitable corrections to Aristotle's hylomorphic depiction of the soul–body relation, I suggest that a rational soul must be present from the moment of conception and that it is at the service of the person. What is of critical importance here is to accept that a human being is present from the moment of conception, something the vast majority of embryologists maintain, notwithstanding the inveiglement of those who state that the pre‐implantation blastocyst is simply a disorganized clump of cells. (shrink)

A Hilbert-style version of an implicational logic can be represented by a set of axiom schemes and modus ponens or by the corresponding axioms, modus ponens and substitution. Certain logics, for example the intuitionistic implicational logic, can also be represented by axioms and the rule of condensed detachment, which combines modus ponens with a minimal form of substitution. Such logics, for example intuitionistic implicational logic, are said to be D-complete. For certain weaker logics, the version based on condensed detachment and (...) axioms (the condensed version of the logic) is weaker than the original. In this paper we prove that the relevant logic T→, and any logic of which this is a sublogic, is D-complete. (shrink)

This essay briefly describes a few of the problems associated with using personhood language to defend the right to life of the pre‐implantation embryo. Arguing that an immaterial soul explains the personal identity of an embryo is problematic for many people because there is no apparent spiritual activity in the unborn. While some scholars argue that the embryo has the potential to act as an adult person and thus should be protected from harm, others contend that potentiality alone is insufficient (...) reason to ascribe special moral worth to the embryo in utero. For Thomas Aquinas, the soul is not only the life‐principle that organizes the human body, but it is also that by which the human being thinks and wills. By making suitable corrections to Aristotle's hylomorphic depiction of the soul–body relation, I suggest that a rational soul must be present from the moment of conception and that it is at the service of the person. What is of critical importance here is to accept that a human being is present from the moment of conception, something the vast majority of embryologists maintain, notwithstanding the inveiglement of those who state that the pre‐implantation blastocyst is simply a disorganized clump of cells. (shrink)

The Alexandrian theologian Origen wrote that God the Father exceeds the Son in a way that surpasses the Son’s own transcendence of creation, and he apparently did so in order to oppose those who disregarded Jesus’ statement that «the Father is greater than I» . Just a few years after Origen’s death, however, when correction of his Son of God theology was well underway, Arius radicalized the latent subordinationism present in Origen’s thought by placing the Son among created things. The (...) Arian tendency to associate the Son with the created realm can be traced back to the attempts of Methodius of Olympus and Eusebius of Caesarea to counter Origen’s doctrine of eternal creation. Arius claimed that Christ is called «Son» because he is the created instrument of God’s will, and he gained sympathy for this voluntaristic view by citing John 14:28. Here was irrefutable scriptural proof of the metaphysical priority of the Father over the Son who is a separate and yet perfect creature of God. (shrink)

In this article I present the Son - Spirit relationship in Christ as the secret to the connection between immanent/economic trinitarian dichotomies without compromising the reality of Christ's human nature. I suggest thatthe Spirit bridges the gap separating God and human beings by linking the inaugurated eschatological present with the future fulfillment of our nascent condition as children of God in Christ. The key notion for understanding God's self-communication rests with the unique role of the Spirit of Christ, who, in (...) the economy, anoints believers in the Son and establishes a real relation between them and God the Father. In effect, the Spirit divinizes all who enter into the risen body of Christ, by activating and bringing to perfection the natural filiation of the Son that is in them by virtue of baptism. This divine gift of participation in the immanent trinitarian life of the Son enables the believer not only to know and love God in a divine way but also to love others as God loves them. (shrink)