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 article reviews the book Jak to jest być świadomym? Analityczne teorie umysłu a problem świadomości [What Is It Like to be Conscious? Analytical Theories of Mind and the Problem of Consciousness], by Józef Bremer.

The primary aim of this study was to investigate the relation between self-perceived executive functions and the school achievement of young adolescents, while controlling for parental education and sex. We specifically focused on executive aspects of daily life behavior and the higher-order EFs, as measured with self-report, rather than on the more basic EFs which have been the primary focus of prior investigations. In two independent samples of sixth graders, students evaluated their EFs on a self-report questionnaire, the Amsterdam Executive (...) Functioning Inventory. School achievement in the domains of mathematics and reading comprehension were evaluated with nationally used, norm-based achievement tests. Results revealed that the self-perceived EFs of young adolescents were significantly correlated with their school achievement in both study samples. School achievement was also correlated with the level of parental education, but the factor sex did not have such influence. In study 1, self-perceived EFs explained additional variance in school achievement, while controlling for parental education and sex. In study 2, this was only the case for the most robust measure of school achievement, i.e., the end-of-primary-school final achievement test. Furthermore, besides the relation with achievement tests, we also found a relation between self-perceived EFs and teacher ratings behavioral problems in the classroom. Together, our findings imply that young students can properly reflect on the effectiveness and appropriateness of their EFs in a way that is relevant to their academic achievement and classroom behavior. The findings underscore the importance of considering the development of EFs and parental education in the evaluation of academic achievements in early adolescence. (shrink)

Three remarks, which are sometimes made about Freud's distiction between Ego and Id are discussed: 1. This distinction would have no analogy in other psychological concepts. 2. The essence of the "I" would be misjudged here. 3. It would be the rest of an atomising psychology, not yet arriving at the modern views of totality. Although the common parlance concerning psychic "parts" has indeed analogies in the old atomistic-psychological conceptions, these instances, as well as the conflicting drives are and have (...) been always considered in psychoanalysis as expressions of which the person himself is the subject. Especially the concept "Id" must be looked at as equivalent to the biological total, to the concept: Person-Stern. The concept I or Ego, as a special structure of "figure" within this whole, means no split-off part, but is equivalent to what is called elsewhere "durchstrukturiertes Unterganze". Freud entitles a certain intern organisation with the word "Ich". He that thinks the essence of "the" I herewith misjudged, confuses word and concept -- the word I contains a lot of equivocations. That there are conflicts within the person is a basic matter of fact, which is not to be pushed aside in favour of totalitarian dogmatics, this conflict must be expressed in our terminology in some way or other. Terms, by way of comparison borrowed from material situations cannot always be avoided, and need not give any inconvenience, provided reflecting over the import of the terms is practised sufficiently. (shrink)

Platónovy pokusy o určení dobra lze nalézt v celém jeho díle. Zahrnují jak relativně „univoční“ koncepci dobra ve smyslu sókratovského intelektualismu, tak pluralističtější koncepci obsaženou v politickém projektu Zákonů. Podle vývojové interpretace Platónových dialogů to naznačuje posun v autorově myšlení způsobený poznáním obtížnosti problému. Byl to přitom údajně teprve Aristotelés, kdo vyřešil Platónův problém dobra pomocí pojmu analogie. Proti této interpretaci článek zdůrazňuje, že aristotelské pojetí analogie je hluboce zakořeněno v Platónově vlastním potýkání se s rozdílem mezi morálním a politickým (...) dobrem. Byla to především Platónovo pochopení specifické hodnoty politické plurality, které stojí v základě akademického rozlišení mezi analogia a pros hen. (shrink)

A number of recent papers have described the successful derivation of egg and sperm precursor cells from mouse embryonic stem cells—so-called “artificial” gametes. Although many scientific questions remain, this research suggests numerous new possibilities for stem cell research and assisted reproductive technology, if a similar breakthrough is achieved with human embryonic stem cells. The novel opportunities raised by artificial gametes also prompt new ethical questions, such as whether same-sex couples should be able to access this technology to have children who (...) are genetically related to them both.THE CREATION OF “ARTIFICIAL” GAMETESOver the past two years, a number of papers have been published detailing the first successful attempts at differentiating mouse embryonic stem cells into egg1 and sperm2 precursor cells. Previously, researchers had used embryonic stem cells to generate tissues such as brain, liver, and pancreatic cells, but not germ cells of any kind. Production of gamete precursor cells was achieved initially through allowing stem cell lines to differentiate more or less randomly, but recent research has focused on identifying the precise ways in which differentiation into gametes can be precipitated and controlled. These breakthroughs make it seem likely that ongoing research on human stem cells will yield similar possibilities,3 raising questions over the practicalities of what might be achieved with such “artificial” gametes. In turn, the novel opportunities presented by artificial gametes raise a number of ethical concerns.The initial breakthrough, namely the obtaining of egg cells from mouse stem cells, was achieved by means of relatively simple science. Rather than coaxing stem cells to develop into eggs using complicated cocktails of growth factors, researchers adopted standard cell culture conditions, but grew the cells at higher density than usual.3–6 Growing the cells in this way led to the formation of ovary-like cell aggregates, which (when separated and stimulated with …. (shrink)

The use of the temporal augment in narrative we have found to be purely scansional. Scansional, too, is the use of the syllabic, though this has a grammatical restriction which is of some interest; indeed, next to the maintenance of type öρovδΕ, it is the most vital fact for the whole question. The unaugmented aorist is not felt as an inflection which has been docked of its first syllable; quite the reverse, the augmented tense is treated as a compound. For (...) example, é normally stands second in its clause; and so, if the syllabic augment was still consciously regarded as what it really is—viz. an adverb in composition—we should expect to see a great unwillingness to place Be after a tense thus augmented. Our expectation is fully borne out by the text; in the whole narrative of the Iliad there are only sixteen sure examples of é standing after the syllabically augmented aorist. (shrink)

Peter Geach supports his case that the religion of Thomas Hobbes was both genuine and a version of Socinianism principally by comparing the theological and scriptural sections of Leviathan with the main doctrines of Socinianism and its latter-day developments in Unitarianism and Christadelphianism. He pays particular attention to comparisons with the Racovian Catechism, the theological writings of Joseph Priestley and the Christadelphian document Christendom Astray by Robert Roberts.

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Spinoza’s Ethics must contain some of philosophy’s most baffling statements. All things are animate; the order and connection of ideas is the same as the order and connection of things: what would I be committed to in agreeing with these doctrines? His austere mode of exposition, sparing of illustrations and discursive explanations, ensures that any answer must be highly speculative.His weakness for dark sayings seems to have communicated itself to some of his best-known commentators. Of course where a philosopher’s thought (...) is itself opaque one would be unreasonable to expect lucidity in a commentator’s exposition of it. However he has been described as holding puzzling, to my mind unintelligible opinions on subjects concerning which, as far as I can see, his own statements more naturally suggest a much clearer and more comprehensible interpretation. There are problems enough in understanding his thought without adding needlessly to the list. I think there has been such an addition in discussion of his doctrines about the causal relationship between God and finite creatures, and this paper is devoted to suggesting another account of his thought on that topic which combines, I think, the advantages of being more intelligible and a more natural construction to place on his own statements, than the set of opinions generally laid at his door. (shrink)

Marion Lee Sanders,1 Anthony James Langone2 1Department of Medicine, Division of Nephrology and Hypertension, University of Iowa, Iowa City, IA, 2Department of Medicine, Division of Nephrology and Hypertension, Vanderbilt University Medical Center, Nashville, TN, USA: Transplantation is the preferred treatment option for individuals with end-stage renal disease. Individuals who undergo transplantation must chronically be maintained on an immunosuppression regimen for rejection prophylaxis to help ensure graft survival. Current rejection prophylaxis consists of using a combination of calcineurin inhibitors, mTOR inhibitors, antimetabolite (...) agents, and/or corticosteroids. These agents have collectively improved the short-term outcomes of renal transplantation, but improvements in late/chronic graft loss and recipient survival have lagged significantly behind challenging the field of transplantation to develop novel prophylactic agents. There have been several clinical trials conducted within the last 5 years in an attempt to bring such novel agents to the commercial market. These trials have resulted in the US Food and Drug Administration approval of extended-release tacrolimus, as well as belatacept, which has the potential to replace calcineurin inhibitors for rejection prophylaxis. Other trials have focused on the development of novel calcineurin inhibitors, costimulation blockade, kinase inhibitors, and inhibitors of leukocyte migration. While these later agents have not been FDA-approved for use in transplantation, they remain noteworthy, as these agents explore pathways not previously targeted for allograft-rejection prophylaxis. The purpose of this review was to consolidate available clinical trial data with regard to the recent developments in rejection prophylaxis in kidney transplantation. Keywords: rejection, prophylaxis, immunosuppression, transplantation. (shrink)

The author deals with the meaning of metamerism. Two contrary points of view may serve to clear the problem. From the morphological point of view probably outgrowth of the organism in longitudinal direction has led to the development of metameres. So the first segmentation is due to a functional differentiation. In Phylogeny this segmentation has been maintained and the originally developed metameres remain the primary morphotic units of the organisms. Further specialising of function and organ-concentration destroyed the original absolute metamerism (...) and only left a rest of the original.The functional point of view renounces an original absolute metamerism for the present moment. It only asks for the functional meaning of the segmentation in organisms, showing this segmentation. From the functional point of view it is possible that metamerism may be the morphological expression of quite different functional requirements and that in one organism the metamerism starts from another system of organs than in another.Es wird gefragt welche Bedeutung die Metamerie haben kann. Zur Erläuterung des Problems werden zwei extremen Betrachtungsweisen einander gegenübergestellt. Nach der morphologischen Betrachtungsweise hat Wachstum der Organismen in die Länge wahrscheinlich zur Ausbildung der Metamerie geführt. Diese erste Metamerie ist wahrscheinlich ein funktioneller Differenzierungsprozess gewesen.In der Phylogenese hat sich diese Metamerie behauptet und die ursprünglich entstandene Metamere sind die primären morphotischen Einheiten der Organismen geblieben. Weitergehende Funktionsspezialisierung und Organkonzentration hat die ursprüngliche absolute Metamerie vernichtet. Was davon übrig blieb sind die Reste der ursprünglichen.Die funktioneile Betrachtungsweise verzichtet vorläufig auf eine ursprüngliche absolute Metamerie. Sie fragt bloss nach der funktionellen Bedeutung, welche die Metamerie besitzt bei denjenigen Organismen, wo diese gefunden wird. Sie achtet es möglich, dass Metamerie der Ausdruck sein kann von ganz verschiedenen funktionellen Anforderungen und dass somit die Metamerie bei der einen Tiergruppe von einem ganz anderen Organsystem ausgeht wei bei einer anderen. (shrink)

William Burnside was one of the three most important algebraists who were involved in the transformation of group theory from its nineteenth-century origins to a deeper twentieth-century subject. Building on work of earlier mathematicians, they were able to develop sophisticated tools for solving difficult problems. His works are of enormous historical importance; they remain also a source of inspiration and information. The works of his contemporaries, such as Klein, Frobenius, Schur, have been published as also have the works of his (...) immediate successors such as Phillip Hall. All of Burnside's papers are reproduced here, organized chronologically and with a detailed bibliography. Walter Feit has contributed a foreword, and a collection of introductory essays are included to provide a commentary on Burnside's work and set it in perspective along with a modern biography that draws on archive material. This is the first reference volume of Burnside's collected papers, enhanced by a series of critical essays on his work, and is important for group theorists and historians and philosophers of mathematics and fills the gap in this area of literature. (shrink)

Routine management of geriatric problems often raises ethical problems, particularly regarding autonomy of the old person. The carers or children may be unaware of the sensitivity of role reversal in dealing with the financial affairs; the need for a residential carer may compromise the old person’s privacy. Attending a day centre confers much benefit, but one must understand the old person’s resistance to change in the proposal of a new daily regimen. Similarly his or her autonomy must be the priority (...) in planning for admittance to an old age home, and not the assumption that the family knows best. A common dilemma is the assessment of an old person’s competency in decision making, either about management of his affairs, or regarding consent to treatment, or participation in research. Because cognitive capacity is not always identical with competency, meaningful tools have recently been developed in which the emphasis is on the specific situation to be investigated. (shrink)

Fraenkel dismissed Epode 11 with the statement that it ‘is an elegant piece of writing, but there is little real life in it’. By this ambiguously expressed comment he did not mean that the poem fails to ‘come alive’, but that it is artificial: he saw the poem as little more than an assembly of themes and motifs which recur in other genres, especially epigram and elegy. This has also been the perspective of some other twentieth-century scholars: Georg Luck's self-styled (...) ‘interpretation’ of the poem consists largely of a numbered list of thirteen motifs which the epode has in common with elegy and which in Luck's opinion were derived by Horace from Gallus. Alessandro Barchiesi, on the other hand, capitalizes on the perceived elegiac motifs in order to see the poem as a dynamic fusion of elegy and iambus. As for commentators, although older representatives seem to have regarded Epode 11 as generally self-explanatory, the poem receives increasing attention from Cavarzere, Mankin and Watson, the last of whom originally discussed some of its problems in a paper published twenty years earlier. Yet various problems still remain, and in this paper I propose to re-examine lines 1–6 and 15–18 in the hope that a clearer view of the epode as a whole may emerge. (shrink)

What can literary education contribute to moral education? In this article the inherent practical, moral or political, relevance of literature and literary education is defended, which is opposed to a moralist approach to (children's) literature. A much debated danger in literature and the arts, viz. that it gives rise to a flight into a "promised land" instead of having relevance for real life and the real world, can be overcome by bringing to the fore the active part the reader plays (...) in realizing the "world of the work." The classical idea of mimesis (i.e. of art mirroring reality) then makes room for a historicity of reading with an ongoing interplay of the (real) worlds of readers and the (fictive) world of the text. This idea is elaborated on from the point of view of Ricoeur's hermeneutics and from that of Iser's reception aesthetics, respectively. In realizing the world of the work the world of the reader is transcended and opened up towards the possible. In this reconfiguration lies the practical relevance of literature. Books, therefore, do not have to mirror the actual world in order to be morally or politically relevant. It is in the act of reading that the lasting significance of so-called classics is renewed time and time again. (shrink)

Lifelines discusses two approaches to biology, “ultra-Darwinism” which Rose criticises, and the “homeodynamic perspective,” which he offers as an alternative. This review suggests that ultra-Darwinism is a caricature of the theoretical positions Rose wishes to oppose and that the homeodynamic perspective is not an alternative, but is complementary to so-called ultra-Darwinism.

Commentators on the Annals naturally observe that the famous first sentence of Tacitus' preface alludes to the preface of Sallust's Bellum Catilinae . But it seems that none of them has observed a further allusion to Sallust's preface in the last sentence of Tacitus', which is almost equally famous.