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Patient-derived xenotransplantation models of human myeloid diseases including acute myeloid leukemia, myelodysplastic syndromes and myeloproliferative neoplasms are essential for studying the biology of the diseases in pre-clinical studies. However, few studies have used these models for comparative purposes. Previous work has shown that acute myeloid leukemia blasts respond to human hematopoietic cytokines whereas myelodysplastic syndrome cells do not. We compared the engraftment of acute myeloid leukemia cells and myelodysplastic syndrome cells in NSG mice to that in NSG-S mice, which have transgene expression of human cytokines. We observed that only 50% of all primary acute myeloid leukemia samples (n=77) transplanted in NSG mice provided useful levels of engraftment (>0.5% human blasts in bone marrow). In contrast, 82% of primary acute myeloid leukemia samples engrafted in NSG-S mice with higher leukemic burden and shortened survival. Additionally, all of 5 injected samples from patients with myelodysplastic syndrome showed persistent engraftment on week 6; however, engraftment was mostly low (

BACKGROUND:Although cytogenetics-based prognostication systems are well described in acute myeloid leukemia (AML), overall survival (OS) remains highly variable within risk groups. An integrated genetic prognostic (IGP) model using cytogenetics plus mutations in nine genes was recently proposed for patients ≤60 years to improve classification. This model has not been validated in clinical practice. METHODS AND FINDINGS:We retrospectively studied 197 patients with newly diagnosed de novo AML. We compared OS curves among the mutational profiles defined by the IGP model. The IGP model assigned patients with intermediate cytogenetics as having favorable, intermediate or unfavorable mutational profiles. The IGP model reassigned 50 of 137 patients with intermediate cytogenetics to favorable or unfavorable mutational profiles. Median OS was 2.8 years among 14 patients with intermediate cytogenetics and favorable mutational profiles (mutant NPM1 and mutant IDH1 or IDH2) and 1.3 years among patients with intermediate mutational profiles. Among patients with intermediate cytogenetics labeled as having unfavorable mutational profiles, median OS was 0.8 years among 24 patients with FLT3-ITD positive AML and high-risk genetic changes (trisomy 8, TET2 and/or DNMT3A) and 1.7 years among 12 patients with FLT3-ITD negative AML and high-risk mutations (TET2, ASXL1 and/or PHF6). OS for patients with intermediate cytogenetics and favorable mutational profiles was similar to OS for patients with favorable cytogenetics (p = 0.697) and different from patients with intermediate cytogenetics and intermediate mutational profiles (p = 0.028). OS among patients with FLT3-ITD positive AML and high-risk genetic changes was similar to patients with unfavorable cytogenetics (p = 0.793) and different from patients with intermediate IGP profile (p = 0.022). Patients with FLT3-ITD negative AML and high-risk mutations, defined as 'unfavorable' in the IGP model, had OS similar to patients with intermediate IGP profile (p = 0.919). CONCLUSIONS:The IGP model was not completely validated in our cohort. However, mutations in six out of the nine genes can be used to characterize survival (NPMI, IDH1, IDH2, FLT3-ITD, TET2, DNMT3A) and allow for more robust prognostication in the patients who are re-categorized by the IGP model. These mutations should be incorporated into clinical testing for younger patients outside of clinical trials, in order to guide therapy.

HOROWITZ, Joel, El radicalismo y el movimiento popular (1916-1930), Edhasa, Buenos Aires, 2015, 320 páginas. ISBN 978-987-628-355-7 BELINI Claudio, Convenciendo al capital. Peronismo, burocracia, empresarios y política industrial, 1943-1955, Imago Mundi, Buenos Aires, 2014. CERUSO Diego, La izquierda en la fábrica. La militancia obrera industrial en el lugar de trabajo, 1916-1943, Imago Mundi, Buenos Aires, 2015, pp. 319.

Semantic incommensurability is understood as non-translatability of concepts taken from different theories. My aim is to give a rational reconstruction of the notion of incommensurability underlying the writings of Feyerabend and the later Kuhn. I claim that incommensurability can be reconstructed on this basis as a coherent conception and that relevant instances can be identified. The translation failure between incommensurable concepts arises from the impossibility to jointly fulfil two conditions of adequacy that the context theory of meaning places on translations. Potential conceptual analogues either fail to preserve the conditions of application or to reproduce the relevant inferential relations. Incommensurability is thus construed as the result of a particular type of conceptual relations which is produced by the incompatibility of the pertinent theories. These conceptual relations are sufficiently tight to make an empirical comparison of the relevant theoretical assertions possible. I try to make these claims plausible by elaborating examples from classical electrodynamics and special relativity.

Previous studies have demonstrated that the small molecule thrombopoietin (TPO) mimetic, eltrombopag (E), induces apoptosis in acute myeloid leukemia (AML) cells. Here, we sought to define the mechanism of the anti-leukemic effect of eltrombopag. Our studies demonstrate that, at a concentration of 5 μM E in 2% serum, E induces apoptosis in leukemia cells by triggering PARP cleavage and activation of caspase cascades within 2-6 hours. The induction of apoptotic enzymes is critically dependent on drug concentration and the concentration of serum. This effect is not associated with an alteration in mitochondrial potential but is associated with a rapid decrease in a reactive oxygen species (ROS) in particular hydrogen peroxide (H2O2). Interestingly, E also decreases mitochondrial maximal and spare respiratory capacities suggesting an induced mitochondrial dysfunction that may not be readily apparent under basal conditions but becomes manifest only under stress. Co-treatment of MOLM14 AML cells with E plus Tempol or H2O2 provides a partial rescue of cell toxicity. Ferric ammonioum citrate (FAC) also antagonized the E induced toxicity, by inducing notable increase in ROS level. Overall, we propose that E dramatically decreases ROS levels leading to a disruption of AML intracellular metabolism and rapid cell death.

INTRODUCTION: Sustainable control of malaria in sub-Saharan Africa is jeopardized by dwindling public health resources resulting from competing health priorities that include an overwhelming acquired immunodeficiency syndrome (AIDS) epidemic. In Mpumalanga province, South Africa, rational planning has historically been hampered by a case surveillance system for malaria that only provided estimates of risk at the magisterial district level (a subdivision of a province). METHODS: To better map control programme activities to their geographical location, the malaria notification system was overhauled and a geographical information system implemented. The introduction of a simplified notification form used only for malaria and a carefully monitored notification system provided the good quality data necessary to support an effective geographical information system. RESULTS: The geographical information system displays data on malaria cases at a village or town level and has proved valuable in stratifying malaria risk within those magisterial districts at highest risk, Barberton and Nkomazi. The conspicuous west-to-east gradient, in which the risk rises sharply towards the Mozambican border (relative risk = 4.12, 95% confidence interval = 3.88-4.46 when the malaria risk within 5 km of the border was compared with the remaining areas in these two districts), allowed development of a targeted approach to control. DISCUSSION: The geographical information system for malaria was enormously valuable in enabling malaria risk at town and village level to be shown. Matching malaria control measures to specific strata of endemic malaria has provided the opportunity for more efficient malaria control in Mpumalanga province.

A partir de la relación entre la Hochschule für Gestaltung de Ulm, Alemania (hfg ulm) y América Latina nace la idea de recorrer la historia institucional de la enseñanza del Diseño en la Argentina a fin de poder interpelar la carrera homónima creada en la Escuela Superior de Bellas Artes de la Universidad Nacional de La Plata (ESBA-UNLP). El planteo del problema centra sus hipótesis en tres núcleos clave: 1) la relación con el modelo económico desarrollista impulsado por la presidencia del Dr. Arturo Frondizi (1958-1962), desde el que se ejecutó un plan sistemático para la industria local; 2) las acciones concretas de valiosos profesores poco reconocidos que dejaron su impronta en algunos centros de enseñanza del ámbito local, nacional e internacional, y 3) los debates en torno a la definición del “diseño” en sus diversas áreas, distinguiendo esta categoría respecto de la arquitectura. En definitiva, se busca articular una “microhistoria” muy específica, que entrelace problemáticas mayores en el campo del Diseño, en un intento por evitar que las distancias entre lo general y lo particular constituyan contrastes inviables.

Our object of study is the neighborhood called Nirvana [in City Bell, district of La Plata], and our aim is to describe the traces left by the landscape dynamics which mark different historical periods, and to relate the concept of landscape with this neighborhood's current territorial configuration. Framed in Cultural Geography, we go back to Milton Santos, Paul Claval and Mario Margulis' perspective, from the category of landscape. The methodology used was qualitative, and it entailed observation and photographic records of the area, informal talks with neighbors, compilation of documents and journalistic material about the area, all of which allowed us to dig deep into what is "public" and what is "private" in this neighborhood, where and how the "outside" and the "inside" are established and to decide whether its aim is being an open and including landscape or if what they are actually after is pushing strangers away by means of invisible barriers

Convergent scientific realism entails that science will sooner or later arrive at the final theory of the fundamental constituents of matter. At that stage, all fundamental truths about nature will be discovered so that the search for basic principle seems bound to come to a halt. I explore options for a non-convergent scientific realism that allows for sustained progress in basic research. I defend the views that the coherence of non-convergent realism requires an emergence claim and that this claim can be supported. I develop the example of the relation between equivalence classes among biological functions and their physiological realizations. Given strongly emergent laws in the sense elaborated in the paper, progress in basic research may survive the discovery of the laws governing the tinymost parts of matter.

Abstract Background Malaria control programmes utilising indoor residual spraying are only effective if a high coverage of targeted structures is achieved and an insecticide that is effective against the specific mosquito vector is correctly applied. Ongoing monitoring of spraying operations is essential to assure optimal programme performance and early corrective action, where indicated. Methods Successful development and application of a computerised spraying operations management system in Mpumalanga Province, South Africa during 1998 resulted in its adaptation and introduction in neighbouring Maputo Province, southern Mozambique during 2000. The structure and components of this computerised management system are described, and its' operational benefit in southern Mozambique, where community-based spray operators apply intradomiciliary insecticide, are reviewed. Conclusions The computerised management system allowed malaria programme management and field supervisors to monitor spraying coverage, insecticide consumption and application rates on an ongoing basis. The system supported a successful transition to community-based spraying, while assuring correct insecticide application and spraying completion according to schedule.