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)

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)

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)

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)

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)

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.

The development and utility of genetically modified crops for smallholders around the world is controversial. Critical questions include what traits and crops are to be developed; how they can be adapted to smallholders’ ecological, social and economic contexts; which dissemination channels should be used to reach smallholders; and which policy environments will enable the greatest benefits for smallholders and the rural poor. A key question is how the voices of smallholders who have experience with or desire to use GM technologies (...) enter the larger debate. Africa has the greatest number of smallholders and poor with the least exposure to GM crops. Because of the well-established use of GM crops in South Africa by commercial farmers, we formed a community of practice involving smallholders, extension, researchers, non-profits and agribusiness in KwaZulu-Natal to examine the conditions under which GM crops are used by smallholders, how smallholders interact with GM technologies and what insights smallholders and other stakeholders can provide regarding these questions. One of the advantages of the CoP approach is that it brings stakeholders together in a non-hierarchical way that encourages new ways of thinking and new partnerships. Such interaction around a specific project can enhance the voice of smallholders in a variety of ways. In our project, smallholder participants have increased their knowledge and can make better decisions about GM technologies, which had been barriers for them. Notably, they have also improved their knowledge of maize production practices, accessed new practice networks, and met new researchers and resource providers. They are now being integrated into these networks in a way that should improve their livelihoods and make the wants and needs of smallholders better known. Such knowledge and experience has improved their voice in agriculture and rural development discussions. (shrink)

L’emploi est au cœur du bien-être d’un individu. Les attentes liées au travail des personnes ayant une déficience intellectuelle ont été comparées à celles des coordonnateurs de services. Les variables comprenaient le type de travail attendu, le nombre d’heures de travail prévu, les préoccupations liées à l’emploi, les mesures de soutien souhaitées sur le lieu de travail et l’influence de la gravité de la déficience intellectuelle et de l’expérience de travail du coordonnateur de services sur les attentes en matière de (...) travail. Les données ont été recueillies auprès de 46 personnes ayant une déficience intellectuelle par le biais d’entretiens et de 46 coordonnateurs au moyen d’un sondage en ligne. Les résultats indiquaient des attentes professionnelles positives globales. Le travail le plus courant attendu était le service et le commerce. L’emploi concurrentiel était attendu plus fréquemment que les ateliers protégés. Alors que les attentes des coordonnateurs de services et des personnes ayant une déficience intellectuelle légère étaient étroitement alignées, il existait une distinction plus grande entre les attentes des coordonnateurs et celles ayant une déficience intellectuelle modérée ou grave. Ces résultats ont des implications importantes pour faciliter le placement des adultes ayant une déficience intellectuelle. (shrink)

The purpose of this paper is to formulate first-order Peano arithmetic within the resources of relevant logic, and to demonstrate certain properties of the system thus formulated. Striking among these properties are the facts that it is trivial that relevant arithmetic is absolutely consistent, but classical first-order Peano arithmetic is straightforwardly contained in relevant arithmetic. Under, I shall show in particular that 0 = 1 is a non-theorem of relevant arithmetic; this, of course, is exactly the formula whose unprovability was (...) sought in the Hilbert program for proving arithmetic consistent. Under, I shall exhibit the requisite translation, drawing some Goedelian conclusions therefrom. Left open, however, is the critical problem whether Ackermann’s rule γ is admissible for theories of relevant arithmetic. The particular system of relevant Peano arithmetic featured in this paper shall be called R♯. Its logical base shall be the system R of relevant implication, taken in its first-order form RQ. Among other Peano arithmetics we shall consider here in particular the systems C♯, J♯, and RM3♯; these are based respectively on the classical logic C, the intuitionistic logic J, and the Sobocinski-Dunn semi-relevant logic RM3. And another feature of the paper will be the presentation of a system of natural deduction for R♯, along lines valid for first-order relevant theories in general. This formulation of R♯ makes it possible to construct relevantly valid arithmetical deductions in an easy and natural way; it is based on, but is in some respects more convenient than, the natural deduction formulations for relevant logics developed by Anderson and Belnap in Entailment. (shrink)

The system R## of "true" relevant arithmetic is got by adding the ω-rule "Infer VxAx from AO, A1, A2, ...." to the system R# of "relevant Peano arithmetic". The rule ⊃E (or "gamma") is admissible for R##. This contrasts with the counterexample to ⊃E for R# (Friedman & Meyer, "Whither Relevant Arithmetic"). There is a Way Up part of the proof, which selects an arbitrary non-theorem C of R## and which builds by generalizing Henkin and Belnap arguments a prime theory (...) T which still lacks C. (The key to the Way Up is a Witness Protection Program, using the ω-rule.) But T may be TOO BIG, whence there is a Way Down argument that produces a better theory TR, such that R## ⊆ TR ⊆ T. (The key to the Way Down is a Metavaluation, on which membership in T is combined with ordinary truth-functional conditions to determine TR.) The result is a theory that is Just Right, whence it never happens that A ⊃ C and A are theorems of R## but C is a non-theorem. (shrink)

C I Lewis showed up Down Under in 2005, in e-mails initiated by Allen Hazen of Melbourne. Their topic was the system Hazen called FL (a Funny Logic), axiomatized in passing in Lewis 1921. I show that FL is the system MEN of material equivalence with negation. But negation plays no special role in MEN. Symbolizing equivalence with → and defining ∼A inferentially as A→f, the theorems of MEN are just those of the underlying theory ME of pure material equivalence. (...) This accords with the treatment of negation in the Abelian l-group logic A of Meyer and Slaney (Abelian logic. Abstract, Journal of Symbolic Logic 46, 425–426, 1981), which also defines ∼A inferentially with no special conditions on f. The paper then concentrates on the pure implicational part AI of A, the simple logic of Abelian groups. The integers Z were known to be characteristic for AI, with every non-theorem B refutable mod some Zn for finite n. Noted here is that AI is pre-tabular, having the Scroggs property that every proper extension SI of AI, closed under substitution and detachment, has some finite Zn as its characteristic matrix. In particular FL is the extension for which n = 2 (Lewis, The structure of logic and its relation to other systems. The Journal of Philosophy 18, 505–516, 1921; Meyer and Slaney, Abelian logic. Abstract. Journal of Symbolic Logic 46, 425–426, 1981; This is an abstract of the much longer paper finally published in 1989 in G. G. Priest, R. Routley and J. Norman, eds., Paraconsistent logic: essays on the inconsistent, Philosophica Verlag, Munich, pp. 245–288, 1989). (shrink)

Based on the relevant logic R, the system R# was proposed as a relevant Peano arithmetic. R# has many nice properties: the most conspicuous theorems of classical Peano arithmetic PA are readily provable therein; it is readily and effectively shown to be nontrivial; it incorporates both intuitionist and classical proof methods. But it is shown here that R# is properly weaker than PA, in the sense that there is a strictly positive theorem QRF of PA which is unprovable in R#. (...) The reason is interesting: if PA is slightly weakened to a subtheory P+, it admits the complex ring C as a model; thus QRF is chosen to be a theorem of PA but false in C. Inasmuch as all strictly positive theorems of R# are already theorems of P+, this nonconservativity result shows that QRF is also a nontheorem of R#. As a consequence, Ackermann's rule γ is inadmissible in R#. Accordingly, an extension of R# which retains its good features is desired. The system R##, got by adding an omega-rule, is such an extension. Central question: is there an effectively axiomatizable system intermediate between R# and R##, which does formalize arithmetic on relevant principles, but also admits γ in a natural way? (shrink)

Modus ponens provides the central theme. There are laws, of the form A→C. A logic L collects such laws. Any datum A provides input to the laws of L. The central ternary relation R relates theories L,T and U, where U consists of all of the outputs C got by applying modus ponens to major premises from L and minor premises from T. Underlying this relation is a modus ponens product operation on theories L and T, whence RLTU iff LTU. (...) These ideas have been expressed, especially with Routley, as worlds semantics for relevant and other substructural logics.Worlds are best demythologized as theories, subject to truth-functional and other constraints. The chief constraint is that theories are taken as closed under logical entailment, which clearly begs the question if we are using the semantics to determine which theory L is Logic itself. Instead we draw the modal logicians’ conclusion—there are many substructural logics, each with its appropriate ternary relational postulates.Each logic L gives rise to a Calculus of L-theories, on which particular candidate logical axioms have the combinatorial properties expected from the well-known Curry–Howard isomorphism . We apply their bubbling lemma, updating the Fools Model of Combinatory Logic at the pure → level for the system BT. We make fusion an explicit connective, proving a combinator correspondence theorem. Having taken relevant → as a left residual for , we explore its right residual mate →r. Finally we concentrate on and prove a finite model property for the classical minimal relevant logic CB, a conservative extension of the minimal positive relevant logic B+. (shrink)

The essays in this volume are based on addresses given during a colloquium on free logic, modal logic, and related areas held at the University of California in 1968. The majority of the contributors are well known for their writings in these fields and their papers are as illuminating as they are technical. In the first paper, Lambert and Bas C. Van Fraassen apply free logic to several controversies in quantified modal logic. One of these is Putman's argument that 'Nothing (...) is both red and green all over' can be had as a theorem of modal logic. Lambert and Van Fraassen provide a counter example to this claim and then show that the argument only holds in systems allowing possible individuals. Jaako Hintikka's essay also deals with 'free' modal logics in much the same way as Hintikka's other papers and discusses some of the criticisms of Quine of the entire enterprise of quantified modal logic. In another paper, H. Leblanc and R. K. Meyer provide truth-value semantics for the theory of types and hence an alternative semantic structure for functional calculi of any order. In addition to these essays, there are papers by R. Thomason and Dana Scott on modal logic, J. Vickers on probability logic, and Peter Woodruff on truth value gaps. To anyone interested in these various areas this collection is sure to be welcome.--R. P. M. (shrink)

The object of this article is to set forth certain evidence that emerges from a study of three of Plutarch's Lives, the Titus, the Paullus, and the Cato Maior, evidence which indicates that these Lives are based upon a definite type of biographical composition, and to suggest its possible origin and date. Since E. Meyer's article on the Cimon of Nepos and Plutarch, biographical sources have generally been assumed for the Greek Lives, and there has been a tendency to make (...) the same assumption for the Roman Lives also, without, however, setting forth the evidence that might justify it. Uxkull Gyllenband maintained that biographies of Greeks and Romans, the sources of Plutarch, were written in the second century b.c., but he gives no evidence for his contention, which is indeed refuted by the observations of Jacoby. Mühl argued with some force that Plutarch's source for the Marcellus was a biography. There is good reason to doubt his conclusion that Plutarch has used a biography of Poseidonius; but the arguments advanced by Klotz for the thesis that the source was the annalist Valerius Antias are still less convincing. Liedmeier postulates a biographical source for the Paullus, but without doing more than asserting the general improbability that Plutarch here used a multiplicity of sources. It seems therefore desirable to collect such evidence as there is of a biographical source in these three Roman Lives of the second century b.c., and it is with such an attempt rather than with a priori considerations that I am here concerned. (shrink)

The title of this and proposed second volume presents the basic idea which unifies the wide variety of topics developed and investigated by the principal authors, major contributing authors, J. M. Dunn and Robert K. Meyer, and eleven other contributors. The other contributors are: J. R. Chidgey, J. A. Coffa, Dorthy L. Grover, Bas van Fraassen, H. Leblanc, Storrs McCall, A. Parks, G. Pottinger, R. Routley, A. Urquhart, and R. G. Wolf. From both the useful analytic table of contents and (...) from the section titles it is clear which contributing author has written each section. Chapter I, "The Pure Calculus of Entailment," suggests how logics of entailment are logics of relevance and necessity. When we explain why a large number of systems are investigated, it will be clear why we write of logics of entailment instead of the logic of entailment. The principal authors build a case in Chapter I, and elsewhere, that a genuinely valid formal inference, viz., a formal entailment, from a formula A to a formula B requires that A be relevant to B in addition to it being impossible that there be an interpretation making A true and B false. So, a claim that A entails B tells us, explicitly or implicitly, that A is relevant to B and that "if A then B" is necessarily true, i.e., A strictly implies B. Consequently since a logic of entailment presents allegedly unfalsifiable claims, i.e., theses, using entailment claims, a logic of entailment presents theses about relevance between antecedents and consequents and necessity. It should be noted that the systems of logic developed are for formal entailments; they may not be logics for material entailments such as: being a cube entails having six surfaces. (shrink)

Neuroscientists are searching for the engram within the conceptual framework established by John Locke's theory of mind. This framework was elaborated before the development of information theory, before the development of information processing machines and the science of computation, before the discovery that molecules carry hereditary information, before the discovery of the codon code and the molecular machinery for editing the messages written in this code and translating it into transcription factors that mark abstract features of organic structure such as (...) anterior and distal. The search for the engram needs to abandon Locke's conceptual framework and work within a framework informed by these developments. The engram is the medium by which information extracted from past experience is transmitted to the computations that inform future behavior. The information-conveying symbols in the engram are rapidly generated in the course of computations, which implies that they are molecules. (shrink)

Cognitive neuroenhancement involves the use of medical interventions to improve normal cognitive functioning such as memory, focus, concentration, or willpower. In this paper I give a Kantian argument defending the use of CNE in science, scholarly research, and creative fields. Kant’s universal law formulation of the categorical imperative shows why enhancement is morally wrong in the familiar contexts of sports or competitive games. This argument, however, does not apply to the use of CNE in higher education, scholarly or scientific research, (...) or creative endeavors such as visual art, fiction or poetry, or musical composition. This is because performance in these areas is embedded within practices that differ in morally significant ways from competitive practices. This important difference provides good reason to think that there is nothing morally wrong with the use of CNE in these areas. My approach is not simply to assume a full-fledged Kantian ethical theory and apply it straight away to the enhancement issue but to establish a reflective equilibrium between our moral intuitions, moral principles that support those intuitions, and the nature of the practices involved. (shrink)

In this article, we describe the social and economic changes that have contributed to contemporary problems of work—family conflict, gender inequality, and risks to children's healthy development. We draw on feminist welfare state scholarship to outline an institutional arrangement that would support an earner—carer society—a social arrangement in which women and men engage symmetrically in paid work and unpaid caregiving and where young children have ample time with their parents. We present a blueprint for work—family reconciliation policies in three areas—paid (...) family-leave provisions, working-time regulations, and early childhood education and care—and we identify key policy design principles. We describe and assess these work—family reconciliation policies as they operate in six European countries widely considered to be policy exemplars: Denmark, Finland, Norway, Sweden, Belgium, and France. We close with an analysis of potential objections to these policies. (shrink)

Papers presented at a seminar held in 2011 organized by the Department of Philosophy, University of Hyderabad.