Os Professores Da Educação Primária Em Formação E As Ciências Naturais: Experiência Anterior, Auto-Percepção E Necessidades De Formação

This paper presents didactic research, developed in the subject of Natural Sciences in the Primary Education Program with the double title of Sciences of Physical Activity and Sports and Primary Education, to inquire about the previous experience, self-perception, and training needs of the future teacher concerning the subject. That is quantitative research. Results arise from the analysis and interpretation of data constituted from the application of a questionnaire. We can conclude that the previous experience of future teachers is very heterogeneous. However, they show a positive attitude towards teaching and learning this subject, valuing and demanding further training both in scientific and didactic content to improve their future teaching practice. It is identified as a challenge for science teaching in this professional profile: to investigate how to achieve a conceptual change, identify the key concepts that teachers must have a deep understanding of to teach the primary science curriculum, assess the degree of understanding them, identify problematic concepts and develop strategies to overcome them.En este trabajo se presenta una investigación didáctica, desarrollada en la asignatura de Ciencias Naturales en el Programa de Educación Primaria con el doble título de Ciencias de la Actividad Física y del Deporte y Educación Primaria, con la finalidad de indagar sobre la experiencia previa, autopercepción y necesidades de formación que tiene el futuro profesor en relación a la asignatura. Esta es una investigación cuantitativa. Los resultados son fruto del análisis e interpretación de los datos constituidos a partir de la aplicación de un cuestionario. Podemos concluir que la experiencia previa de los futuros maestros es muy heterogénea y, sin embargo, manifiestan una actitud positiva hacia la enseñanza y hacia el aprendizaje de esta asignatura, valorando y demandando una mayor formación, tanto en contenido científico como didáctico para la mejora de su futura práctica docente. Se identifica como reto para la enseñanza de las ciencias en este perfil profesional: investigar sobre cómo lograr un cambio conceptual, identificando los conceptos clave en que los maestros deben tener una profunda comprensión para poder enseñar el currículum de ciencias de primaria, evaluar el grado de comprensión de los mismos, identificar los conceptos problemáticos y desarrollar estrategias para superarlos.Este trabalho apresenta uma investigação didáctica, desenvolvida na disciplina de Ciências Naturais no Grau do Ensino Primário e no duplo Grau de Actividade Física e Ciências do Desporto e Ensino Primário, com o objectivo de investigar a experiência anterior, auto-percepção e necessidades de formação de futuros professores em relação ao tema. A metodologia utilizada é quantitativa e os resultados obtidos são o resultado da análise e interpretação dos dados obtidos através do preenchimento de um questionário. Os resultados indicam que a experiência anterior dos futuros professores é muito heterogénea e, no entanto, mostram uma atitude positiva em relação ao ensino e aprendizagem desta disciplina, valorizando e exigindo mais formação, tanto em conteúdo científico como didático a fim de melhorar a sua prática pedagógica futura. O desafio para o ensino das ciências neste perfil profissional é identificado como: investigar como conseguir uma mudança conceptual, identificando os conceitos-chave sobre os quais os professores devem ter uma compreensão profunda para poderem ensinar o currículo das ciências primárias, avaliando o grau de compreensão destes conceitos, identificando conceitos problemáticos e desenvolvendo estratégias para os ultrapassar

Mechanism of localization of the magnetization reversal in 3 nm wide Co nanowires

The mechanism of magnetization reversal has been studied in a model system of self-assembled cobalt nanowires with a 3 nm diameter. The structure, orientation and size of grains within the nanowires could be determined by high resolution transmission electron microscopy. The magnetic properties were probed using static and dynamic magnetization measurements. Micromagnetic modeling based on the structural analysis allows us to correlate the structure and the magnetic behavior of the wires, revealing competition between shape anisotropy, magnetocrystalline anisotropy and exchange in the localized reversal within Co hcp oriented grains. These results provide direct experimental evidence of the link between anisotropy fluctuations and reversal localization in nanowires.Fil: Vidal, F.. Universite de Paris Vi. Institut Des Nanosciences de Paris; FranciaFil: Zheng, Y.. Universite de Paris Vi. Institut Des Nanosciences de Paris; FranciaFil: Schio, P.. Universidade Federal Do Sao Carlos; Brasil. Universite de Paris Vi. Institut Des Nanosciences de Paris; FranciaFil: Bonilla, F. J.. Universite de Paris Vi. Institut Des Nanosciences de Paris; FranciaFil: Barturen, Mariana. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universite de Paris Vi. Institut Des Nanosciences de Paris; Francia. Comisión Nacional de Energía Atómica. Gerencia del Area de Investigación y Aplicaciones No Nucleares. Gerencia de Física (Centro Atómico Bariloche); Argentina. Comisión Nacional de Energía Atómica. Gerencia del Area de Energía Nuclear. Instituto Balseiro; Argentina. Universidad Nacional de Cuyo; ArgentinaFil: Milano, Julian. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universite de Paris Vi. Institut Des Nanosciences de Paris; Francia. Comisión Nacional de Energía Atómica. Gerencia del Area de Investigación y Aplicaciones No Nucleares. Gerencia de Física (Centro Atómico Bariloche); Argentina. Universidad Nacional de Cuyo; Argentina. Comisión Nacional de Energía Atómica. Gerencia del Area de Energía Nuclear. Instituto Balseiro; ArgentinaFil: Demaille, D.. Universite de Paris Vi. Institut Des Nanosciences de Paris; FranciaFil: Fonda, E.. L’Orme des Merisiers Saint-Aubin. Synchrotron Soleil; FranciaFil: de Oliveira, A. J. A.. Universidade Federal Do Sao Carlos; BrasilFil: Etgens, V. H.. Universite de Paris Vi. Institut Des Nanosciences de Paris; Francia. Fédération Lavoisier Franklin; Franci

MethylExtract: High-Quality methylation maps and SNV calling from whole genome bisulfite sequencing data

[v2; ref status: indexed, http://f1000r.es/301]Whole genome methylation profiling at a single cytosine resolution is now feasible due to the advent of high-throughput sequencing techniques together with bisulfite treatment of the DNA. To obtain the methylation value of each individual cytosine, the bisulfite-treated sequence reads are first aligned to a reference genome, and then the profiling of the methylation levels is done from the alignments. A huge effort has been made to quickly and correctly align the reads and many different algorithms and programs to do this have been created. However, the second step is just as crucial and non-trivial, but much less attention has been paid to the final inference of the methylation states. Important error sources do exist, such as sequencing errors, bisulfite failure, clonal reads, and single nucleotide variants. We developed MethylExtract, a user friendly tool to: i) generate high quality, whole genome methylation maps and ii) detect sequence variation within the same sample preparation. The program is implemented into a single script and takes into account all major error sources. MethylExtract detects variation (SNVs – Single Nucleotide Variants) in a similar way to VarScan, a very sensitive method extensively used in SNV and genotype calling based on non-bisulfite-treated reads. The usefulness of MethylExtract is shown by means of extensive benchmarking based on artificial bisulfite-treated reads and a comparison to a recently published method, called Bis-SNP. MethylExtract is able to detect SNVs within High-Throughput Sequencing experiments of bisulfite treated DNA at the same time as it generates high quality methylation maps. This simultaneous detection of DNA methylation and sequence variation is crucial for many downstream analyses, for example when deciphering the impact of SNVs on differential methylation. An exclusive feature of MethylExtract, in comparison with existing software, is the possibility to assess the bisulfite failure in a statistical way. The source code, tutorial and artificial bisulfite datasets are available at http://bioinfo2.ugr.es/MethylExtract/ and http://sourceforge.net/projects/methylextract/, and also permanently accessible from 10.5281/zenodo.7144.This work was supported by the Spanish Government [BIO2008-01353 to JLO and BIO2010-20219 to MH], and Basque country 'AE' grant (GB)

Cuidados Intensivos de Anestesia: recomendaciones de la Sección de Cuidados Intensivos de la SEDAR: Monedero P, Paz Martín D, Cardona Pereto J, Barturen F, Fernández Quero L, Aguilera Celorrio L, et al. Cuidados Intensivos de Anestesia: recomendaciones de la Sección de Cuidados Intensivos de la SEDAR. Rev Esp Anestesiol Reanim. 2017;64(5):282-285. doi: 10.1016/j.redar.2016.12.007. PMID: 28258746

Las directrices europeas de formación especializada en Anestesiología son responsabilidad del European Board of Anaesthesiology (EBA UEMS), a través de su comité permanente de Educación y Desarrollo Profesional. Estas directrices han sido aprobadas por el UEMS Council, y en ellas se definen los cuidados intensivos como una competencia central de la especialidad de Anestesiología. A diferencia de otras competencias específicas, la «atención médica y perioperatoria de pacientes críticos/Cuidados Intensivos Generales» es considerada un dominio de competencias básicas que debe alcanzar todo especialista en Anestesiología en Europa. Para alcanzar el conjunto de competencias de la especialidad, las «Normas europeas de formación postgrado de especialistas médicos» en sus «Requisitos de Capacitación para la Especialidad de Anestesiología, Dolor y Medicina de Cuidados Intensivos» establece un tiempo mínimo de formación de 5 años, de los cuales hasta un año puede dirigirse específicamente a la formación en Medicina de Cuidados Intensivos

Pyrazoleamide compounds are potent antimalarials that target Na+ homeostasis in intraerythrocytic Plasmodium falciparum

The quest for new antimalarial drugs, especially those with novel modes of action, is essential in the face of emerging drug-resistant parasites. Here we describe a new chemical class of molecules, pyrazoleamides, with potent activity against human malaria parasites and showing remarkably rapid parasite clearance in an in vivo model. Investigations involving pyrazoleamide-resistant parasites, whole-genome sequencing and gene transfers reveal that mutations in two proteins, a calcium-dependent protein kinase (PfCDPK5) and a P-type cation-ATPase (PfATP4), are necessary to impart full resistance to these compounds. A pyrazoleamide compound causes a rapid disruption of Na+ regulation in blood-stage Plasmodium falciparum parasites. Similar effect on Na+ homeostasis was recently reported for spiroindolones, which are antimalarials of a chemical class quite distinct from pyrazoleamides. Our results reveal that disruption of Na+ homeostasis in malaria parasites is a promising mode of antimalarial action mediated by at least two distinct chemical classes

Trisubstituted Pyrimidines as Efficacious and Fast-acting Antimalarials

In this paper we describe the optimization of a phenotypic hit against Plasmodium falciparum, based on a trisubstituted pyrimidine scaffold. This led to compounds with good pharmacokinetics and oral activity in a P. berghei mouse model of malaria. The most promising compound (13) showed a reduction in parasitemia of 96% when dosed at 30 mg/kg orally once a day for 4 days in the P. berghei mouse model of malaria. It also demonstrated a rapid rate of clearance of the erythrocytic stage of P. falciparum in the SCID mouse model with an ED90 of 11.7 mg/kg when dosed orally. Unfortunately, the compound is a potent inhibitor of cytochrome P450 enzymes, probably due to a 4-pyridyl substituent. Nevertheless, this is a lead molecule with a potentially useful antimalarial profile, which could either be further optimized or be used for target hunting

Characterization of Novel Antimalarial Compound ACT-451840: Preclinical Assessment of Activity and Dose-Efficacy Modeling.

BACKGROUND: Artemisinin resistance observed in Southeast Asia threatens the continued use of artemisinin-based combination therapy in endemic countries. Additionally, the diversity of chemical mode of action in the global portfolio of marketed antimalarials is extremely limited. Addressing the urgent need for the development of new antimalarials, a chemical class of potent antimalarial compounds with a novel mode of action was recently identified. Herein, the preclinical characterization of one of these compounds, ACT-451840, conducted in partnership with academic and industrial groups is presented. METHOD AND FINDINGS: The properties of ACT-451840 are described, including its spectrum of activities against multiple life cycle stages of the human malaria parasite Plasmodium falciparum (asexual and sexual) and Plasmodium vivax (asexual) as well as oral in vivo efficacies in two murine malaria models that permit infection with the human and the rodent parasites P. falciparum and Plasmodium berghei, respectively. In vitro, ACT-451840 showed a 50% inhibition concentration of 0.4 nM (standard deviation [SD]: ± 0.0 nM) against the drug-sensitive P. falciparum NF54 strain. The 90% effective doses in the in vivo efficacy models were 3.7 mg/kg against P. falciparum (95% confidence interval: 3.3-4.9 mg/kg) and 13 mg/kg against P. berghei (95% confidence interval: 11-16 mg/kg). ACT-451840 potently prevented male gamete formation from the gametocyte stage with a 50% inhibition concentration of 5.89 nM (SD: ± 1.80 nM) and dose-dependently blocked oocyst development in the mosquito with a 50% inhibitory concentration of 30 nM (range: 23-39). The compound's preclinical safety profile is presented and is in line with the published results of the first-in-man study in healthy male participants, in whom ACT-451840 was well tolerated. Pharmacokinetic/pharmacodynamic (PK/PD) modeling was applied using efficacy in the murine models (defined either as antimalarial activity or as survival) in relation to area under the concentration versus time curve (AUC), maximum observed plasma concentration (Cmax), and time above a threshold concentration. The determination of the dose-efficacy relationship of ACT-451840 under curative conditions in rodent malaria models allowed prediction of the human efficacious exposure. CONCLUSION: The dual activity of ACT-451840 against asexual and sexual stages of P. falciparum and the activity on P. vivax have the potential to meet the specific profile of a target compound that could replace the fast-acting artemisinin component and harbor additional gametocytocidal activity and, thereby, transmission-blocking properties. The fast parasite reduction ratio (PRR) and gametocytocidal effect of ACT-451840 were recently also confirmed in a clinical proof-of-concept (POC) study

Preclinical characterization and target validation of the antimalarial pantothenamide MMV693183

Drug resistance and a dire lack of transmission-blocking antimalarials hamper malaria elimination. Here, we present the pantothenamide MMV693183 as a first-in-class acetyl-CoA synthetase (AcAS) inhibitor to enter preclinical development. Our studies demonstrate attractive drug-like properties and in vivo efficacy in a humanized mouse model of Plasmodium falciparum infection. The compound shows single digit nanomolar in vitro activity against P. falciparum and P. vivax clinical isolates, and potently blocks P. falciparum transmission to Anopheles mosquitoes. Genetic and biochemical studies identify AcAS as the target of the MMV693183-derived antimetabolite, CoA-MMV693183. Pharmacokinetic-pharmacodynamic modelling predict that a single 30 mg oral dose is sufficient to cure a malaria infection in humans. Toxicology studies in rats indicate a > 30-fold safety margin in relation to the predicted human efficacious exposure. In conclusion, MMV693183 represents a promising candidate for further (pre)clinical development with a novel mode of action for treatment of malaria and blocking transmission

The antimalarial MMV688533 provides potential for single-dose cures with a high barrier to

The emergence and spread of Plasmodium falciparum resistance to first-line antimalarials creates an imperative to identify and develop potent preclinical candidates with distinct modes of action. Here, we report the identification of MMV688533, an acylguanidine that was developed following a whole-cell screen with compounds known to hit high-value targets in human cells. MMV688533 displays fast parasite clearance in vitro and is not cross-resistant with known antimalarials. In a P. falciparum NSG mouse model, MMV688533 displays a long-lasting pharmacokinetic profile and excellent safety. Selection studies reveal a low propensity for resistance, with modest loss of potency mediated by point mutations in PfACG1 and PfEHD. These proteins are implicated in intracellular trafficking, lipid utilization, and endocytosis, suggesting interference with these pathways as a potential mode of action. This preclinical candidate may offer the potential for a single low-dose cure for malaria