Methotrexate polyglutamates as a potential marker of adherence to long-term therapy in children with juvenile idiopathic arthritis and juvenile dermatomyositis: an observational, cross-sectional study

Introduction: Methotrexate (MTX) is a cornerstone of treatment in a wide variety of inflammatory conditions, including juvenile idiopathic arthritis (JIA) and juvenile dermatomyositis (JDM). However, owing to its narrow therapeutic index and the considerable interpatient variability in clinical response, monitoring of adherence to MTX is important. The present study demonstrates the feasibility of using methotrexate polyglutamates (MTXPGs) as a biomarker to measure adherence to MTX treatment in children with JIA and JDM.
Methods: Data were collected prospectively from a cohort of 48 children (median age 11.5 years) who received oral or subcutaneous (SC) MTX therapy for JIA or JDM. Dried blood spot samples were obtained from children by finger pick at the clinic or via self- or parent-led sampling at home, and they were analysed to determine the variability in MTXPG concentrations and assess adherence to MTX therapy.
Results: Wide fluctuations in MTXPG total concentrations (>2.0-fold variations) were found in 17 patients receiving stable weekly doses of MTX, which is indicative of nonadherence or partial adherence to MTX therapy. Age (P = 0.026) and route of administration (P = 0.005) were the most important predictors of nonadherence to MTX treatment. In addition, the study showed that MTX dose and route of administration were significantly associated with variations in the distribution of MTXPG subtypes. Higher doses and SC administration of MTX produced higher levels of total MTXPGs and selective accumulation of longer-chain MTXPGs (P < 0.001 and P < 0.0001, respectively).
Conclusions: Nonadherence to MTX therapy is a significant problem in children with JIA and JDM. The present study suggests that patients with inadequate adherence and/or intolerance to oral MTX may benefit from SC administration of the drug. The clinical utility of MTXPG levels to monitor and optimise adherence to MTX in children has been demonstrated.Trial Registration: ISRCTN Registry identifier: ISRCTN93945409 . Registered 2 December 2011.

English and English literature : complete study and revision guide.

Guía actualizada de acuerdo con las modificaciones del contenido curricular. Contiene todo lo que los estudiantes necesitan saber para lograr superar el General Certificate of Secundary Education (GCSE) de inglés y literatura inglesa. Ha sido escrito por un examinador para ayudar en el aprendizaje de los alumnos y orientar su revisión. Su contenido se puede utilizar como obra de referencia, para apoyar el estudio a lo largo del curso, o como para una revisión para la preparación de los exámenes. El estudio de textos de teatro, novelas y cuentos se centra en antes y después de mil novecientos catorce. Ofrece comentarios en el margen de algunas páginas para llamar la atención del estudiante sobre puntos importantes que de otro modo podría perder. Al final de cada sección hay ejemplos de preguntas GCSE y preguntas de examen práctico. Las respuestas a las preguntas de examen, simulacros de exámenes e índice de documentos se encuentran al final de la publicación.

AQA English and English literature.

Guía actualizada de acuerdo con las modificaciones del contenido curricular. Contiene todo lo que los estudiantes necesitan saber para lograr superar el General Certificate of Secundary Education (GCSE) de inglés y literatura inglesa. Ha sido escrito por un examinador para ayudar en el aprendizaje de los alumnos y orientar su revisión. Su contenido se puede utilizar como obra de referencia, para apoyar el estudio a lo largo del curso, o como para una revisión para la preparación de los exámenes. El estudio de textos de teatro, novelas y cuentos se centra en antes y después de mil novecientos catorce. Ofrece comentarios en el margen de algunas páginas para llamar la atención del estudiante sobre puntos importantes que de otro modo podría perder. Al final de cada sección hay ejemplos de preguntas GCSE y preguntas de examen práctico. Las respuestas a las preguntas de examen, simulacros de exámenes e índice de documentos se encuentran al final de la publicación.

AQA English and English literature : revision guide.

Esta guía ofrece ayuda a los estudiantes para gestionar la revisión de sus conocimientos en lengua y literatura y preparar los exámenes del General Certificate of Secundary Education (GCSE) de manera eficiente. El contenido de este título se divide en seis secciones:puntuación, expresión oral y escrita; escritos y los medios de comunicación; Shakespeare, plan de ensayo de La tempestad; poesía ; novelas y cuentos; asesoramiento de examen. Al final de cada sección hay preguntas prácticas para reforzar lo aprendido. Las soluciones, junto con un índice, en las últimas páginas de la publicación.

AQA English and English literature. Workbook.

Libro de trabajo que ayudará a los estudiantes que estén preparando la lengua y literatura para el General Certificate of Secundary Education (GCSE), a acostumbrarse al estilo de las preguntas utilizadas en los exámenes. El contenido de este título se divide en seis secciones:puntuación, hablar y escuchar; escritos y los medios de comunicación; Shakespeare ; novelas y cuentos; prácticas de exámenes y modelos de respuestas. Las soluciones, junto con un índice, en las últimas páginas de la publicación.

Revise WJEC : GCSE english and english literature.

Prepara a los alumnos para los cursos WJEC GCSE de inglés y WJEC GCSE de literatura inglesa, es decir, para el General Certificate Secondary Education en Galés. Ofrece muestras de preguntas y respuestas de los exámenes, junto con comentarios de los examinadores a estas respuestas y consejos para mejorarlas. También, proporciona un apartado para localizar y recuperar información, en el que se repasan las cuestiones principales de cada capítulo, así como un CD-ROM con material complementario.

Of mice and men : literature guide for GCSE.

Guía de lectura para la obra 'De ratones y hombres' del autor estadounidense John Steinbeck, que ayuda a los estudiantes que estén preparando el examen GCSE (General Certificate of Secondary Education) a entender la novela. Incluye un análisis del argumento, de la estructura de la novela y de sus personajes, una sección sobre el autor y el contexto histórico, comentarios sobre el texto de la obra y preguntas para afianzar los conocimientos del texto con respuestas al final del libro.

English as a Second Language and Children’s literature : An empirical study on Swedish elementary school teachers’ methods and attitudes towards the use of children’s literature in the English classroom

Previous research has shown multiple benefits and challenges with the incorporation of children’s literature in the English as a Second language (ESL) classroom. In addition, the use of children’s literature in the lower elementary English classroom is recommended by the Swedish National Agency for Education. Consequently, the current study explores how teachers in Swedish elementary school teach ESL through children’s literature. This empirical study involves English teachers from seven schools in a small municipality in Sweden. The data has been collected through an Internet survey. The study also connects the results to previous international research, comparing Swedish and international research. The results suggest that even though there are many benefits of using children’s literature in the ESL classroom, the respondents seldom use these authentic texts, due to limited time and a narrow supply of literature, among other factors. However, despite these challenges, all of the teachers claim to use children’s literature by reading aloud in the classroom. Based on the results, further research exploring pupils’ thoughts in contrast to teachers would be beneficial. In addition, the majority of the participants expressed that they wanted more information on how to use children’s literature. Therefore, additional research relating to beneficial methods of teaching English through children’s literature, especially in Sweden, is recommended.

Longitudinal distribution and lateral pattern of megalopal settlement and juvenile recruitment of Carcinus maenas (L.) (Brachyura, Portunidae) in the Mira River Estuary, Portugal

Settlement is a critical process in the life history of crabs, and thus affecting the abundance, distribution and structure of estuarine communities. The spatial pattern of settlement of megalopae of the shore crab Carcinus maenas along a longitudinal estuarine gradient (Mira River Estuary, Portugal) was examined, as well as its effects on the juvenile population. To measure megalopal settlement, four replicate collectors were deployed in six equally spaced stations along the estuarine axis. Juveniles were collected on the same locations with a quadrat randomly deployed on the substrate. To assess fine-scale megalopal settlement within a curved region of the estuary, replicate collectors were deployed on both margins along Moinho da Asneira curve. Megalopae settled differently along the six longitudinal points, with a tendency to attenuate their settlement upstream. Within the curved region, megalopae preferentially settled on the left margin collectors, probably due to the weaker velocity speeds felt on this margin. Concerning the overall juvenile density, there were significant differences among the stations distributed along the estuary, but they did no reflect a longitudinal dispersion attenuation pattern. Size-frequency distribution of the juvenile population showed that the average size is higher on the left margin. Recruits (carapace length between 1.0 mm and 3.4 mm) were more abundant on the upstream stations. Density of early juveniles (3.4 mm-6.5 mm) and juveniles (6.5 mm-10 mm) was more stable throughout the estuary axis than that of recruits. This distribution pattern may result from tidal excursion processes or mechanisms to avoid biotic interactions, such as predation and competition. (c) 2006 Elsevier Ltd. All rights reserved.

Determination of fiber length and juvenile and mature wood zones from Hevea brasiliensis trees grown in Brazil

The aim of this study was to verify the average fiber length and the juvenile and mature wood zones from Hevea brasiliensis proveniences from a reforestation area in São Paulo, Brazil. For this purpose, five Hevea brasiliensis trees were randomly collected from a 50-year-old plantation, located in Balsamo, São Paulo, Brazil. The trees were cut and five flat sawn boards were obtained. The juvenile and mature wood zones were determined by fiber length measurement from the pith to the bark. The results showed that: (a) the juvenile wood of this species occurred approx. between 40 and 55 mm, from the pith, and from this point forward, the mature wood zone was found; (b) there was a significant difference between the average fiber length of juvenile wood (1.26 mm) and mature wood (1.51 mm).

The megalopa and juvenile development of Pachygrapsus transversus (Gibbes, 1850) (Decapoda, Brahyura) compared with other grapsid crabs

Megalopae were reared in the laboratory to the 7(th) crab stage. The megalopa and 1(st) crab stage are described and juvenile development was studied with emphasis on pleopodal differentiation. The megalopal phase, is easily identified, and shares with those of other Grapsinae and Plagusiinae big size, the presence of many natatory setae, and a series of conspicuous teeth on the inner margin of the dactyli from the 2(nd) to 4(th) walking leg. These features are regarded as adaptive for settlement in a wave-swept environment, such as the rocky marine intertidal where most of those species live. Fast development of juvenile pleopods is another characteristic of these subfamilies. In Pachygrapsus transversus, the sexes can be distinguished from the 2(nd) crab stage. Gonopod differentiation in males and the basic segmentation of all four pleopod pairs in females are already concluded at the 5(th) instar. A review of the available information indicated that settlement of large megalopae and fast juvenile development, preceding a precocious sexual maturity, are trends in Grapsinae and Plagusiinae. on the other hand, the Sesarminae pass through a more extensive juvenile instar sequence and presumably a delayed maturity.

Tolerance to the air exposition test of Hoplias lacerdae larvae and juvenile during its initial development

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Treatment of pediatric myelodysplastic syndromes and juvenile myelomonocytic leukemia: the Brazilian experience in the past decade

Background: Therapy strategies for myelodysplastic syndromes (MDS) and juvenile myelomonocytic leukemia (JMML) vary considerably. Objective: To review the treatment of Brazilian children who were diagnosed with MDS or JMML in the past decade and reported to the Brazilian Cooperative Group on Pediatric Myelodysplastic syndromes (BCG-MDS-PED). Results: of 173 children reported to the BCG-MDS-PED from January 1997 to January 2003 with a suspected diagnosis of MDS or JMML, 91 had the diagnosis confirmed after central review of the bone marrow aspirate and biopsy. Information on previous treatments was available for 78 MDS/JMML patients. Treatment varied from different schedules of low-dose (14%) and standard-dose chemotherapy (50%), granulocyte-colony-stimulating factor (G-CSF 7%), interferon (5%), steroids (2%) and erythropoietin (2%) to allogeneic stem-cell transplantation (SCT) (14%). No survival advantage could be demonstrated based on Hasle's classification or based on treatment. Conclusion: This report reflects the current practice in treating Brazilian children with MDS/JMML without specific Cooperative Group guidelines. Treatment modalities were very heterogeneous. The strategies for implementing a national protocol should consider international guidelines and focus on local experience and available resources. (C) 2004 Elsevier Ltd. All rights reserved.