852 resultados para Medicaments antineoplàstics -- Efectes secundaris


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L’acer és un dels materials més destacats dins l’àmbit estructural degut, en gran part, a laseva elevada capacitat tensional, tant en tracció com en compressió. Aquesta capacitatpermet estructures lleugeres i cobrir grans llums. En pòrtics de nusos rígids d’una nauindustrial és habitual l’ús de perfils oberts en doble T. Aquests perfils presenten una baixarigidesa a torsió i flexió lateral, el qual els fa propensos a patir inestabilitat quan es produeixcompressió en una de les seves ales en flexió, fenòmen que es coneix com a vinclamentlateral. Per aquest motiu, el càlcul en efectes de 2n ordre adquireix una importància mésrellevant a l’hora de dimensionar els elements estructurals. Un altre punt important és queels elements estructurals estan units entre ells, no treballen de manera individual, fet quecomporta un estudi més complex a l’hora de determinar les condicions de contorn de cadaelement.El present estudi pretén determinar l'efecte estabilitzador de les corretges en un pòrtic denusos rígids, i si és així, en quina magnitud pot arribar a afectar aquest grau de travat alconjunt estructural.L'Estudi s'ha realitzat seguint dues metodologies diferents. Els anàlisis estructurals parteixendels criteris indicats a les normatives d'estructures metàl•liques espanyola (CTE-DB-SE-A) il'europea (Eurocodig 3)

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BACKGROUND: The need for an integrated view of data obtained from high-throughput technologies gave rise to network analyses. These are especially useful to rationalize how external perturbations propagate through the expression of genes. To address this issue in the case of drug resistance, we constructed biological association networks of genes differentially expressed in cell lines resistant to methotrexate (MTX). METHODS: Seven cell lines representative of different types of cancer, including colon cancer (HT29 and Caco2), breast cancer (MCF-7 and MDA-MB-468), pancreatic cancer (MIA PaCa-2), erythroblastic leukemia (K562) and osteosarcoma (Saos-2), were used. The differential expression pattern between sensitive and MTX-resistant cells was determined by whole human genome microarrays and analyzed with the GeneSpring GX software package. Genes deregulated in common between the different cancer cell lines served to generate biological association networks using the Pathway Architect software. RESULTS: Dikkopf homolog-1 (DKK1) is a highly interconnected node in the network generated with genes in common between the two colon cancer cell lines, and functional validations of this target using small interfering RNAs (siRNAs) showed a chemosensitization toward MTX. Members of the UDP-glucuronosyltransferase 1A (UGT1A) family formed a network of genes differentially expressed in the two breast cancer cell lines. siRNA treatment against UGT1A also showed an increase in MTX sensitivity. Eukaryotic translation elongation factor 1 alpha 1 (EEF1A1) was overexpressed among the pancreatic cancer, leukemia and osteosarcoma cell lines, and siRNA treatment against EEF1A1 produced a chemosensitization toward MTX. CONCLUSIONS: Biological association networks identified DKK1, UGT1As and EEF1A1 as important gene nodes in MTX-resistance. Treatments using siRNA technology against these three genes showed chemosensitization toward MTX.

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Background: Vorapaxar is a new oral protease-activatedreceptor 1 (PAR-1) antagonist that inhibits thrombin-induced platelet activation. Methods: In this multinational, double-blind, randomized trial, we compared vorapaxar with placebo in 12,944 patients who had acute coronary syndromes without ST-segment elevation. The primary end point was a composite of death from cardiovascular causes, myocardial infarction, stroke, recurrent ischemia with rehospitalization, or urgent coronary revascularization. RESULTS: Follow-up in the trial was terminated early after a safety review. After a median follow-up of 502 days (interquartile range, 349 to 667), the primary end point occurred in 1031 of 6473 patients receiving vorapaxar versus 1102 of 6471 patients receiving placebo (KaplanMeier 2-year rate, 18.5% vs. 19.9%; hazard ratio, 0.92; 95% confidence interval [CI], 0.85 to 1.01; P = 0.07). A composite of death from cardiovascular causes, myocardial infarction, or stroke occurred in 822 patients in the vorapaxar group versus 910 in the placebo group (14.7% and 16.4%, respectively; hazard ratio, 0.89; 95% CI, 0.81 to 0.98; P = 0.02). Rates of moderate and severe bleeding were 7.2% in the vorapaxar group and 5.2% in the placebo group (hazard ratio, 1.35; 95% CI, 1.16 to 1.58; P<0.001). Intracranial hemorrhage rates were 1.1% and 0.2%, respectively (hazard ratio, 3.39; 95% CI, 1.78 to 6.45; P<0.001). Rates of nonhemorrhagic adverse events were similar in the two groups. Conclusions: In patients with acute coronary syndromes, the addition of vorapaxar to standard therapy did not significantly reduce the primary composite end point but significantly increased the risk of major bleeding, including intracranial hemorrhage. (Funded by Merck; TRACER ClinicalTrials.gov number, NCT00527943.)

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Background: Methotrexate is a chemotherapeutic agent used to treat a variety of cancers. However, the occurrence of resistance limits its effectiveness. Cytochrome c in its reduced state is less capable of triggering the apoptotic cascade. Thus, we set up to study the relationship among redox state of cytochrome c, apoptosis and the development of resistance to methotrexate in MCF7 human breast cancer cells. Results: Cell incubation with cytochrome c-reducing agents, such as tetramethylphenylenediamine, ascorbate or reduced glutathione, decreased the mortality and apoptosis triggered by methotrexate. Conversely, depletion of glutathione increased the apoptotic action of methotrexate, showing an involvement of cytochrome c redox state in methotrexateinduced apoptosis. Methotrexate-resistant MCF7 cells showed increased levels of endogenous reduced glutathione and a higher capability to reduce exogenous cytochrome c. Using functional genomics we detected the overexpression of GSTM1 and GSTM4 in methotrexate-resistant MCF7 breast cancer cells, and determined that methotrexate was susceptible of glutathionylation by GSTs. The inhibition of these GSTM isoforms caused an increase in methotrexate cytotoxicity in sensitive and resistant cells. Conclusions: We conclude that overexpression of specific GSTMs, GSTM1 and GSTM4, together with increased endogenous reduced glutathione levels help to maintain a more reduced state of cytochrome c which, in turn, would decrease apoptosis, thus contributing to methotrexate resistance in human MCF7 breast cancer cells.

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An enantioselective approach to (-)-isoavenaciolide was achieved starting from 1- undecyn-3-ol. The synthesis relied upon the preparation of a chiral 4-silyloxy-2-alkenylborane by hydroboration of a protected 2,3-allenol and subsequent stereoselective addition to 2- thiophenecarboxaldehyde

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[spa] Este texto forma parte de un proyecto de investigación Los efectos de los cambios sociales en el trabajo y la vida profesional de los docentes universitarios, parcialmente financiado por el Ministerio de Ciencia e Innovación (SEJ2006-01876), en el que nos planteamos explorar los cambios los ámbitos de la legislación, laorganización institucional, la investigación, la gestión y la docencia en los últimos treinta años. El principal objetivo del estudio era profundizar en nuestra comprensión sobre el impacto del cambio económico, social, cultural, tecnológico y laboral que están experimentando las universidades españolas en la vida y la identidad profesional del personal docente e investigador, teniendo en cuenta el contexto nacional y europeo. Estapublicación recoge la 24 historias de vida profesional realizas con o sobre otros tantos docentes universitarios. Sus relatos analizados y contextualizados, significan una contribución significativa al conocimiento basado en la investigación sobre el saber profesional y la experiencia laboral en las universidades españolas, y en consecuencia, a nuestra comprensión sobre cómo los académicos se están enfrentando con los cambios actuales.

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[spa] Este texto forma parte de un proyecto de investigación Los efectos de los cambios sociales en el trabajo y la vida profesional de los docentes universitarios, parcialmente financiado por el Ministerio de Ciencia e Innovación (SEJ2006-01876), en el que nos planteamos explorar los cambios los ámbitos de la legislación, laorganización institucional, la investigación, la gestión y la docencia en los últimos treinta años. El principal objetivo del estudio era profundizar en nuestra comprensión sobre el impacto del cambio económico, social, cultural, tecnológico y laboral que están experimentando las universidades españolas en la vida y la identidad profesional del personal docente e investigador, teniendo en cuenta el contexto nacional y europeo. Estapublicación recoge la 24 historias de vida profesional realizas con o sobre otros tantos docentes universitarios. Sus relatos analizados y contextualizados, significan una contribución significativa al conocimiento basado en la investigación sobre el saber profesional y la experiencia laboral en las universidades españolas, y en consecuencia, a nuestra comprensión sobre cómo los académicos se están enfrentando con los cambios actuales.

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[spa] Este texto forma parte de un proyecto de investigación Los efectos de los cambios sociales en el trabajo y la vida profesional de los docentes universitarios, parcialmente financiado por el Ministerio de Ciencia e Innovación (SEJ2006-01876), en el que nos planteamos explorar los cambios los ámbitos de la legislación, laorganización institucional, la investigación, la gestión y la docencia en los últimos treinta años. El principal objetivo del estudio era profundizar en nuestra comprensión sobre el impacto del cambio económico, social, cultural, tecnológico y laboral que están experimentando las universidades españolas en la vida y la identidad profesional del personal docente e investigador, teniendo en cuenta el contexto nacional y europeo. Estapublicación recoge la 24 historias de vida profesional realizas con o sobre otros tantos docentes universitarios. Sus relatos analizados y contextualizados, significan una contribución significativa al conocimiento basado en la investigación sobre el saber profesional y la experiencia laboral en las universidades españolas, y en consecuencia, a nuestra comprensión sobre cómo los académicos se están enfrentando con los cambios actuales.

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[spa] Este texto forma parte de un proyecto de investigación Los efectos de los cambios sociales en el trabajo y la vida profesional de los docentes universitarios, parcialmente financiado por el Ministerio de Ciencia e Innovación (SEJ2006-01876), en el que nos planteamos explorar los cambios los ámbitos de la legislación, laorganización institucional, la investigación, la gestión y la docencia en los últimos treinta años. El principal objetivo del estudio era profundizar en nuestra comprensión sobre el impacto del cambio económico, social, cultural, tecnológico y laboral que están experimentando las universidades españolas en la vida y la identidad profesional del personal docente e investigador, teniendo en cuenta el contexto nacional y europeo. Estapublicación recoge la 24 historias de vida profesional realizas con o sobre otros tantos docentes universitarios. Sus relatos analizados y contextualizados, significan una contribución significativa al conocimiento basado en la investigación sobre el saber profesional y la experiencia laboral en las universidades españolas, y en consecuencia, a nuestra comprensión sobre cómo los académicos se están enfrentando con los cambios actuales.

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The age at which school children begin instruction in the foreign language has been brought forward on two main grounds: (1) young children are better language learners than older children, and (2) bilingualism brings cognitive advantages to children. Both statements are critically analysed in this paper. First of all, recent research findings show that the advantage that younger learners show in a naturalistic language learning situation (or through school immersion) disappears in a formal language learning situation with very limited exposure to the target language. Secondly, the positive effects on cognitive development that have been revealed through research correspond to situations of balanced bilingualism, that is, situations in which children have a high command of the two languages. In contrast, children¿s command of the foreign language in our context is very limited and hence far from the situation of balanced bilingualism (or trilingualism) that is said to bring positive cognitive effects.

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The purpose of this article is to treat a currently much debated issue, the effects of age on second language learning. To do so, we contrast data collected by our research team from over one thousand seven hundred young and adult learners with four popular beliefs or generalizations, which, while deeply rooted in this society, are not always corroborated by our data.Two of these generalizations about Second Language Acquisition (languages spoken in the social context) seem to be widely accepted: a) older children, adolescents and adults are quicker and more efficient at the first stages of learning than are younger learners; b) in a natural context children with an early start are more liable to attain higher levels of proficiency. However, in the context of Foreign Language Acquisition, the context in which we collect the data, this second generalization is difficult to verify due to the low number of instructional hours (a maximum of some 800 hours) and the lower levels of language exposure time provided. The design of our research project has allowed us to study differences observed with respect to the age of onset (ranging from 2 to 18+), but in this article we focus on students who began English instruction at the age of 8 (LOGSE Educational System) and those who began at the age of 11 (EGB). We have collected data from both groups after a period of 200 (Time 1) and 416 instructional hours (Time 2), and we are currently collecting data after a period of 726 instructional hours (Time 3). We have designed and administered a variety of tests: tests on English production and reception, both oral and written, and within both academic and communicative oriented approaches, on the learners' L1 (Spanish and Catalan), as well as a questionnaire eliciting personal and sociolinguistic information. The questions we address and the relevant empirical evidence are as follows: 1. "For young children, learning languages is a game. They enjoy it more than adults."Our data demonstrate that the situation is not quite so. Firstly, both at the levels of Primary and Secondary education (ranging from 70.5% in 11-year-olds to 89% in 14-year-olds) students have a positive attitude towards learning English. Secondly, there is a difference between the two groups with respect to the factors they cite as responsible for their motivation to learn English: the younger students cite intrinsic factors, such as the games they play, the methodology used and the teacher, whereas the older students cite extrinsic factors, such as the role of their knowledge of English in the achievement of their future professional goals. 2 ."Young children have more resources to learn languages." Here our data suggest just the opposite. The ability to employ learning strategies (actions or steps used) increases with age. Older learners' strategies are more varied and cognitively more complex. In contrast, younger learners depend more on their interlocutor and external resources and therefore have a lower level of autonomy in their learning. 3. "Young children don't talk much but understand a lot"This third generalization does seem to be confirmed, at least to a certain extent, by our data in relation to the analysis of differences due to the age factor and productive use of the target language. As seen above, the comparably slower progress of the younger learners is confirmed. Our analysis of interpersonal receptive abilities demonstrates as well the advantage of the older learners. Nevertheless, with respect to passive receptive activities (for example, simple recognition of words or sentences) no great differences are observed. Statistical analyses suggest that in this test, in contrast to the others analyzed, the dominance of the subjects' L1s (reflecting a cognitive capacity that grows with age) has no significant influence on the learning process. 4. "The sooner they begin, the better their results will be in written language"This is not either completely confirmed in our research. First of all, we perceive that certain compensatory strategies disappear only with age, but not with the number of instructional hours. Secondly, given an identical number of instructional hours, the older subjects obtain better results. With respect to our analysis of data from subjects of the same age (12 years old) but with a different number of instructional hours (200 and 416 respectively, as they began at the ages of 11 and 8), we observe that those who began earlier excel only in the area of lexical fluency. In conclusion, the superior rate of older learners appears to be due to their higher level of cognitive development, a factor which allows them to benefit more from formal or explicit instruction in the school context. Younger learners, however, do not benefit from the quantity and quality of linguistic exposure typical of a natural acquisition context in which they would be allowed to make use of implicit learning abilities. It seems clear, then, that the initiative in this country to begin foreign language instruction earlier will have positive effects only if it occurs in combination with either higher levels of exposure time to the foreign language, or, alternatively, with its use as the language of instruction in other areas of the curriculum.

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The age at which school children begin instruction in the foreign language has been brought forward on two main grounds: (1) young children are better language learners than older children, and (2) bilingualism brings cognitive advantages to children. Both statements are critically analysed in this paper. First of all, recent research findings show that the advantage that younger learners show in a naturalistic language learning situation (or through school immersion) disappears in a formal language learning situation with very limited exposure to the target language. Secondly, the positive effects on cognitive development that have been revealed through research correspond to situations of balanced bilingualism, that is, situations in which children have a high command of the two languages. In contrast, children¿s command of the foreign language in our context is very limited and hence far from the situation of balanced bilingualism (or trilingualism) that is said to bring positive cognitive effects.

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The purpose of this article is to treat a currently much debated issue, the effects of age on second language learning. To do so, we contrast data collected by our research team from over one thousand seven hundred young and adult learners with four popular beliefs or generalizations, which, while deeply rooted in this society, are not always corroborated by our data.Two of these generalizations about Second Language Acquisition (languages spoken in the social context) seem to be widely accepted: a) older children, adolescents and adults are quicker and more efficient at the first stages of learning than are younger learners; b) in a natural context children with an early start are more liable to attain higher levels of proficiency. However, in the context of Foreign Language Acquisition, the context in which we collect the data, this second generalization is difficult to verify due to the low number of instructional hours (a maximum of some 800 hours) and the lower levels of language exposure time provided. The design of our research project has allowed us to study differences observed with respect to the age of onset (ranging from 2 to 18+), but in this article we focus on students who began English instruction at the age of 8 (LOGSE Educational System) and those who began at the age of 11 (EGB). We have collected data from both groups after a period of 200 (Time 1) and 416 instructional hours (Time 2), and we are currently collecting data after a period of 726 instructional hours (Time 3). We have designed and administered a variety of tests: tests on English production and reception, both oral and written, and within both academic and communicative oriented approaches, on the learners' L1 (Spanish and Catalan), as well as a questionnaire eliciting personal and sociolinguistic information. The questions we address and the relevant empirical evidence are as follows: 1. "For young children, learning languages is a game. They enjoy it more than adults."Our data demonstrate that the situation is not quite so. Firstly, both at the levels of Primary and Secondary education (ranging from 70.5% in 11-year-olds to 89% in 14-year-olds) students have a positive attitude towards learning English. Secondly, there is a difference between the two groups with respect to the factors they cite as responsible for their motivation to learn English: the younger students cite intrinsic factors, such as the games they play, the methodology used and the teacher, whereas the older students cite extrinsic factors, such as the role of their knowledge of English in the achievement of their future professional goals. 2 ."Young children have more resources to learn languages." Here our data suggest just the opposite. The ability to employ learning strategies (actions or steps used) increases with age. Older learners' strategies are more varied and cognitively more complex. In contrast, younger learners depend more on their interlocutor and external resources and therefore have a lower level of autonomy in their learning. 3. "Young children don't talk much but understand a lot"This third generalization does seem to be confirmed, at least to a certain extent, by our data in relation to the analysis of differences due to the age factor and productive use of the target language. As seen above, the comparably slower progress of the younger learners is confirmed. Our analysis of interpersonal receptive abilities demonstrates as well the advantage of the older learners. Nevertheless, with respect to passive receptive activities (for example, simple recognition of words or sentences) no great differences are observed. Statistical analyses suggest that in this test, in contrast to the others analyzed, the dominance of the subjects' L1s (reflecting a cognitive capacity that grows with age) has no significant influence on the learning process. 4. "The sooner they begin, the better their results will be in written language"This is not either completely confirmed in our research. First of all, we perceive that certain compensatory strategies disappear only with age, but not with the number of instructional hours. Secondly, given an identical number of instructional hours, the older subjects obtain better results. With respect to our analysis of data from subjects of the same age (12 years old) but with a different number of instructional hours (200 and 416 respectively, as they began at the ages of 11 and 8), we observe that those who began earlier excel only in the area of lexical fluency. In conclusion, the superior rate of older learners appears to be due to their higher level of cognitive development, a factor which allows them to benefit more from formal or explicit instruction in the school context. Younger learners, however, do not benefit from the quantity and quality of linguistic exposure typical of a natural acquisition context in which they would be allowed to make use of implicit learning abilities. It seems clear, then, that the initiative in this country to begin foreign language instruction earlier will have positive effects only if it occurs in combination with either higher levels of exposure time to the foreign language, or, alternatively, with its use as the language of instruction in other areas of the curriculum.

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L’envelliment és un procés personal, multidimensional i de canvi constant que té lloc al llarg de tota la nostra vida. Amb independència de l’existència de malaltia, amb l’edat el nostre organisme experimenta canvis en els diferents sistemes, que suposen el seu deteriorament. L’adquisició d’un estil de vida saludable, és determinant per mantenir un envelliment òptim. L’activitat física esdevé un instrument útil per minimitzar els efectes de la progressiva pèrdua de funcionalitat, fins i tot en persones de més edat i més fràgils. Per aquest motiu, en les persones grans es recomana participar en programes d’activitat física, i la seva pràctica. Per al disseny i desenvolupament d’aquestes pràctiques cal tenir en compte l’estat biològic de la gent gran, les recomanacions de prescripció d'exercici físic, les barreres i factors d’èxit de les intervencions en aquest col·lectiu. A Catalunya, les pràctiques físiques i esportives vinculades a les persones grans han experimentat una ràpida evolució durant els darrers anys, convertint-se en un important instrument a considerar entre els professionals encarregats de les polítiques de salut. Dia a dia augmenta la consciència entre aquest col·lectiu de la importància que té la pràctica d’activitat física en la prevenció de malalties cròniques i l’augment de l’esperança de vida.

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Aquest estudi va analitzar la interacció del canvi organitzatiu, els valors culturals i el canvi tecnològic en el sistema sanitari català. L'estudi se subdivideix en cinc parts diferents. La primera és una anàlisi de contingut de webs relacionats amb la salut a Catalunya. La segona és un estudi dels usos d'Internet en qüestions relacionades amb la salut entre la població en general, les associacions de pacients i els professionals de la salut, i es basa en un sondeig per Internet adaptat a cada un d'aquests grups. La tercera part és un estudi de treball de camp dels programes experimentals duts a terme pel Govern català en diverses àrees i hospitals locals per a integrar electrònicament la història clínica dels pacients. La quarta és un estudi de les implicacions organitzatives de la introducció de sistemes d'informació en la gestió d'hospitals i centres d'assistència primària a l'Institut Català de Salut, el principal proveïdor de salut pública a Catalunya, i es basa en un sondeig per Internet i entrevistes en profunditat. La cinquena part és un estudi de cas dels efectes organitzatius i socials de la introducció de les tecnologies de la informació i la comunicació en un dels principals hospitals de Catalunya, l'Hospital Clínic de Barcelona. L'estudi es va dur a terme entre el maig del 2005 i el juliol del 2007.