449 research outputs found

    Teachers' and students' views and attitudes towards a new mathematics curriculum: A case study

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    The education system in Portugal is in the midst of a period of intensive reform. This paper describes the findings of a qualitative case study focusing on the views and attitudes of teachers and students participating in a pilot curriculum development programme stressing active methodologies and group work, conducted by the Ministry of Education In particular it discusses their views and attitudes about mathematics, mathematics teaching and curriculum innovation. The teachers were found to struggle with a contradiction: whilst they approved the new orientations, which were seen as adequate and innovative, they complained strongly about the design and implementation of the programme Students had a generally positive attitude towards mathematics, although there were differences among them. The 7th graders were satisfied with their mathematics classes and with the new curriculum. The 10th graders did not consider the changes as significant in themselves, but expressed concern for their academic progress

    Roadmap to cure multiple myeloma

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    Despite significant advances in the treatment of multiple myeloma which had led to unprecedented rates of response and survival, patients still relapse, and cure remains elusive. We propose in this review a roadmap to achieve the dream of cure for multiple myeloma based on five complementary strategies. First, to increase knowledge about disease pathogenesis with a focus on the biology of circulating tumor cells, responsible for dissemination and extramedullary disease, and minimal residual disease clones who represent the reservoir of clonal evolution and disease recurrence. Second, to consider undetectable measurable residual disease (MRD), defined by high-sensitive techniques, as the new endpoint of therapy. Third, to treat disease causation instead of symptomatology through early detection and intervention. Thereby, by treating high-risk smoldering myeloma patients early, we may not only contribute to delay disease progression into active disease but also to increase the cure rates. Fourth, to use the most active scheme in standard-risk patients if the cure is in the horizon. Fifth, to investigate experimental therapies in newly diagnosed patients with high-risk MM, implementing early rescue intervention strategies with the goal of eradicating all tumor clones, and achieving minimal residual disease negativity

    Murine muscle engineered from dermal precursors: an in vitro model for skeletal muscle generation, degeneration and fatty infiltration.

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    Skeletal muscle can be engineered by converting dermal precursors into muscle progenitors and differentiated myocytes. However, the efficiency of muscle development remains relatively low and it is currently unclear if this is due to poor characterization of the myogenic precursors, the protocols used for cell differentiation, or a combination of both. In this study, we characterized myogenic precursors present in murine dermospheres, and evaluated mature myotubes grown in a novel three-dimensional culture system. After 57 days of differentiation, we observed isolated, twitching myotubes followed by spontaneous contractions of the entire tissue-engineered muscle construct on an extracellular matrix (ECM). In vitro engineered myofibers expressed canonical muscle markers and exhibited a skeletal (not cardiac) muscle ultrastructure, with numerous striations and the presence of aligned, enlarged mitochondria, intertwined with sarcoplasmic reticula (SR). Engineered myofibers exhibited Na+- and Ca2+-dependent inward currents upon acetylcholine (ACh) stimulation and tetrodotoxin-sensitive spontaneous action potentials. Moreover, ACh, nicotine, and caffeine elicited cytosolic Ca2+ transients; fiber contractions coupled to these Ca2+ transients suggest that Ca2+ entry is activating calcium-induced calcium release from the SR. Blockade by d-tubocurarine of ACh-elicited inward currents and Ca2+ transients suggests nicotinic receptor involvement. Interestingly, after 1 month, engineered muscle constructs showed progressive degradation of the myofibers concomitant with fatty infiltration, paralleling the natural course of muscular degeneration. We conclude that mature myofibers may be differentiated on the ECM from myogenic precursor cells present in murine dermospheres, in an in vitro system that mimics some characteristics found in aging and muscular degeneration

    Maternal fish consumption, fatty acid levels and angiogenic factors: The Generation R Study

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    Introduction Angiogenic factors, such as placental growth factor (PlGF) and soluble Flt-1 (sFlt-1), are key regulators of placental vascular development. Evidence from in vitro studies indicates that fatty acids can affect angiogenesis. We investigated the associations of maternal fish consumption and fatty acids levels with angiogenic factors during pregnancy, and in cord blood in a large population-based prospective cohort. Methods First trimester fish consumption was assessed among 3134 pregnant women using a food-frequency questionnaire. Plasma fatty acid levels were measured in second trimester. Plasma PlGF and sFlt-1 were measured in first and second trimester and in cord blood. Associations of fish consumption or fatty acid levels with angiogenic factors were assessed by multivariable linear regression analyses. Results There were no consistent associations of total fish or lean fish consumption with levels of PlGF, sFlt-1, or sFlt-1/PlGF ratio. Neither fatty fish nor shellfish were associated with angiogenic factors. Plasma omega-3 polyunsaturated fatty acids, which are the main type of fatty acids in fish, were inconsistently associated with angiogenic factors in second trimester and cord blood. Yet, higher levels of arachidonic acid, an omega-6 polyunsaturated fatty acid, were associated with lower levels of PlGF and sFlt-1. Discussion We found no consistent associations of fish consumption or fatty acids levels with angiogenic factors in a population with low fish consumption. Studies including populations with higher fish consumption are required to fully grasp the potential effects of maternal fish consumption on placental angiogenesis

    CAR T-Cells in Multiple Myeloma Are Ready for Prime Time

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    The survival of patients with multiple myeloma (MM) has been dramatically improved in the last decade thanks to the incorporation of second-generation proteasome inhibitors (PI), immunomodulatory drugs (IMID), and, more recently, anti-CD38 monoclonal antibodies (MoAb). Nevertheless, still, a major proportion of MM patients will relapse, underscoring the need for new therapies in this disease. Moreover, survival in patients failing the current standard of care regimens (including PI, IMIDs, and anti-CD38 MoAb), which is now defined as triple-class refractory, remains dismal, and new drugs with different mechanism of action are needed. B-cell maturation antigen (BCMA)-targeted therapies and in particular chimeric antigen receptor T cell (CAR T-cell) treatment have emerged as promising platforms to overcome refractoriness to conventional drugs. In this manuscript, we review the current available data regarding CAR T-cell therapy for MM, with a special focus on target selection, clinical results, limitations, and future strategies

    Monitoring Guidance for Underwater Noise in European Seas- Part II: Monitoring Guidance Specifications

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    This document has been prepared by the Technical Subgroup on Underwater Noise and other forms of Energy (TSG Noise), established in 2010 by the Marine Directors, i.e. the representatives of directorates or units in European Union Member States, Acceding Countries, Candidate Countries and EFTA Member States dealing with or responsible for marine issues. In December 2011, the Marine Directors requested the TSG Noise to provide monitoring guidance that could be used by Member States in establishing monitoring schemes to meet the needs of the Marine Strategy Framework Directive indicators for underwater noise in their marine waters. This document presents the recommendations and information needed to commence the monitoring required for underwater noise.JRC.H.1-Water Resource

    Monitoring Guidance for Underwater Noise in European Seas - Part I: Executive Summary

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    This document has been prepared by the Technical Subgroup on Underwater Noise and other forms of Energy (TSG Noise), established in 2010 by the Marine Directors, i.e. the representatives of directorates or units in European Union Member States, Acceding Countries, Candidate Countries and EFTA Member States dealing with or responsible for marine issues. In December 2011, the Marine Directors requested the TSG Noise to provide monitoring guidance that could be used by Member States in establishing monitoring schemes to meet the needs of the Marine Strategy Framework Directive indicators for underwater noise in their marine waters. This document presents the key conclusions and recommendations that support the implementation of the practical guidance to commence the monitoring required for underwater noise.JRC.H.1-Water Resource

    Folate, vitamin B12, and homocysteine in smoking-exposed pregnant women: A systematic review

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    Smoking exposure is associated with pregnancy complications, as are levels of folate, vitamin B12, and homocysteine. In nonpregnant adults, smoking exposure is associated negatively with folate and vitamin B12 levels and positively with homocysteine levels. A complete overview of the literature on this topic in pregnant women is lacking. To evaluate evidence of associations of maternal smoking exposure during pregnancy and levels of folate, homocysteine, and vitamin B12 in pregnancy and in cord blood, we searched MEDLINE, Embase, CINAHL, Cochrane, Scopus, Web of Science, and reference lists of relevant studies until August 2017. We selected studies in pregnant women describing the association of passive or active smoking and levels of folate, homocysteine, and/or vitamin B12. Data were extracted by two independent reviewers. We included 32 studies of 2,015 identified references with a total of 37,822 participants and more than 6,000 smokers. Twenty-eight studies measured folate, 14 measured vitamin B12, and 13 measured homocysteine. Nineteen out of 28 studies assessing folate reported significantly lower levels in pregnant women exposed to smoking compared with those unexposed. Vitamin B12 levels were lower in smoking mothers in eight out of 14 studies. Homocysteine levels tended to be higher in mothers exposed to smoking. Smoking exposure during pregnancy is generally associated with lower folate and vitamin B12 levels and higher homocysteine levels. This may help raise further awareness about the consequences of smoking and the need to encourage stopping smoking in all, especially in pregnant women
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