A indisciplina no 1.º ciclo: conceções e práticas dos professores

Relatório de Estágio apresentado à Escola Superior de Educação de Lisboa para obtenção de grau de mestre em Ensino do 1.º e 2.º ciclos do Ensino Básico

First-cycle rash and survival in patients with advanced non-small-cell lung cancer receiving cetuximab in combination with first-line chemotherapy : a subgroup analysis of data from the FLEX phase 3 study

Background: The randomised phase 3 First-Line Erbitux in Lung Cancer (FLEX) study showed that the addition of cetuximab to cisplatin and vinorelbine significantly improved overall survival compared with chemotherapy alone in the first-line treatment of advanced non-small-cell lung cancer (NSCLC). The main cetuximab-related side-effect was acne-like rash. Here, we assessed the association of this acne-like rash with clinical benefit. Methods: We did a subgroup analysis of patients in the FLEX study, which enrolled patients with advanced NSCLC whose tumours expressed epidermal growth factor receptor. Our landmark analysis assessed if the development of acne-like rash in the first 21 days of treatment (first-cycle rash) was associated with clinical outcome, on the basis of patients in the intention-to-treat population alive on day 21. The FLEX study is registered with ClinicalTrials.gov, number NCT00148798. Findings: 518 patients in the chemotherapy plus cetuximab group-290 of whom had first-cycle rash-and 540 patients in the chemotherapy alone group were alive on day 21. Patients in the chemotherapy plus cetuximab group with first-cycle rash had significantly prolonged overall survival compared with patients in the same treatment group without first-cycle rash (median 15·0 months [95% CI 12·8-16·4] vs 8·8 months [7·6-11·1]; hazard ratio [HR] 0·631 [0·515-0·774]; p<0·0001). Corresponding significant associations were also noted for progression-free survival (median 5·4 months [5·2-5·7] vs 4·3 months [4·1-5·3]; HR 0·741 [0·607-0·905]; p=0·0031) and response (rate 44·8% [39·0-50·8] vs 32·0% [26·0-38·5]; odds ratio 1·703 [1·186-2·448]; p=0·0039). Overall survival for patients without first-cycle rash was similar to that of patients that received chemotherapy alone (median 8·8 months [7·6-11·1] vs 10·3 months [9·6-11·3]; HR 1·085 [0·910-1·293]; p=0·36). The significant overall survival benefit for patients with first-cycle rash versus without was seen in all histology subgroups: adenocarcinoma (median 16·9 months, [14·1-20·6] vs 9·3 months [7·7-13·2]; HR 0·614 [0·453-0·832]; p=0·0015), squamous-cell carcinoma (median 13·2 months [10·6-16·0] vs 8·1 months [6·7-12·6]; HR 0·659 [0·472-0·921]; p=0·014), and carcinomas of other histology (median 12·6 months [9·2-16·4] vs 6·9 months [5·2-11·0]; HR 0·616 [0·392-0·966]; p=0·033). Interpretation: First-cycle rash was associated with a better outcome in patients with advanced NSCLC who received cisplatin and vinorelbine plus cetuximab as a first-line treatment. First-cycle rash might be a surrogate clinical marker that could be used to tailor cetuximab treatment for advanced NSCLC to those patients who would be most likely to derive a significant benefit. Funding: Merck KGaA. © 2011 Elsevier Ltd.

The Personal tutorial guidance sessions in the framework of the teaching-learning field of the Bologna process: University of Minho (first cycle) courses students’ perceptions

The Bologna Process defends the adoption of a higher education in teaching-learning methodologies that – in contraposition to the previous model based on the transmission of knowledge, which for being essentially theoretical, gives the student a passive role in the knowledge construction process – allows a (pro) active, autonomous and practical learning, where the student acquires and develops his competences. The personal tutorial guidance sessions are included in the teaching contact hours. This abstract presents a study about the University of Minho (first cycle) Courses Students’ perceptions of the personal tutorial guidance sessions’ relevance in the scope of the learning-teaching process, so as to confirm if the implementation/implantation of the commonly called tutorial (type) education, as an approach to an active, autonomous and practical learning, is sensed by the learners themselves

Extra activities for the English class in the first cycle of Primary School. 'Actividades extra para la clase de inglés del primer ciclo de Educación Primaria'.

Resumen basado en el de los autores. Trabajo al que se le concedió una ayuda para la creación de materiales curriculares interactivos en el año 2003

Ethyl-eicosapentaenoic acid in first-episode psychosis : a 1H-MRS study

Ethyl-eicosapentaenoic acid (E-EPA) is an omega-3 fatty acid that has been used in a range of neuropsychiatric conditions with some benefits. However, its mechanism of action is unknown. Here, we investigate its effects on in vivo brain metabolism in first-episode psychosis (FEP). Proton magnetic resonance spectroscopy at 3 T was performed in the temporal lobes of 24 FEP patients before and after 12 weeks of treatment in the context of a larger double-blind, placebo-controlled E-EPA augmentation study. Treatment group effects for glutathione (F1,12=6.1, p=0.03), and a hemisphere-by-group interaction for glutamine/glutamate (F1,20=4.4, p=0.049) were found. Glutathione increased bilaterally and glutamate/glutamine increased in the left hemisphere following E-EPA administration. Improvement in negative symptoms correlated with metabolic brain changes, particularly glutathione (r=-0.57). These results suggest that E-EPA augmentation alters glutathione availability and modulates the glutamine/glutamate cycle in early psychosis, with some of the metabolic brain changes being correlated with negative symptom improvement. Larger confirmatory studies of these postulated metabolic brain effects of E-EPA are warranted.

Incorporating sustainability measures in life-cycle financial decision making for highway construction

Public awareness and the nature of highway construction works demand that sustainability measures are first on the development agenda. However, in the current economic climate, individual volition and enthusiasm for such high capital investments do not present as strong cases for decision making as the financial pictures of pursuing sustainability. Some stakeholders consider sustainability to be extra work that costs additional money. Though, stakeholders realised its importance in infrastructure development. They are keen to identify the available alternatives and financial implications on a lifecycle basis. Highway infrastructure development is a complex rocess which requires expertise and tools to evaluate investment options, such as environmentally sustainable features for road and highway development. Life-cycle cost analysis (LCCA) is a valuable approach for investment decision making for construction works. However, LCCA applications in highway development are still limited. Current models, for example focus on economic issues alone and do not deal with sustainability factors, which are more difficult to quantify and encapsulate in estimation modules. This paper reports the research which identifies sustainability related factors in highway construction projects, in quantitative and qualitative forms of a multi-criteria analysis. These factors are then incorporated into past and proven LCCA models to produce a new long term decision support model. The research via questionnaire, model building, analytical hierarchy processes (AHP) and case studies have identified, evaluated and then processed highway sustainability related cost elements. These cost elements need to be verified by industry before being integrated for further development of the model. Then the Australian construction industry will have a practical tool to evaluate investment decisions which provide an optimum balance between financial viability and sustainability deliverables.

The importance of environmental issues and costs in Life Cycle Cost Analysis (LCCA) for highway projects

Sustainability has been increasingly recognised as an integral part of highway infrastructure development. In practice however, the fact that financial return is still a project’s top priority for many, environmental aspects tend to be overlooked or considered as a burden, as they add to project costs. Sustainability and its implications have a far-reaching effect on each project over time. Therefore, with highway infrastructure’s long-term life span and huge capital demand, the consideration of environmental cost/ benefit issues is more crucial in life-cycle cost analysis (LCCA). To date, there is little in existing literature studies on viable estimation methods for environmental costs. This situation presents the potential for focused studies on environmental costs and issues in the context of life-cycle cost analysis. This paper discusses a research project which aims to integrate the environmental cost elements and issues into a conceptual framework for life cycle costing analysis for highway projects. Cost elements and issues concerning the environment were first identified through literature. Through questionnaires, these environmental cost elements will be validated by practitioners before their consolidation into the extension of existing and worked models of life-cycle costing analysis (LCCA). A holistic decision support framework is being developed to assist highway infrastructure stakeholders to evaluate their investment decision. This will generate financial returns while maximising environmental benefits and sustainability outcome.

Intensity-dependent asymmetric photoionization in few-cycle laser pulses

The asymmetric photoionization of atoms irradiated by intense, few-cycle laser pulses is studied numerically. The results show that the pulse intensity affects the asymmetric photoionization in three aspects. First, at higher intensities, the asymmetry becomes distinctive for few-cycle pulses of longer durations. Second, as the laser intensity increases, the maximal asymmetry first decreases then increases after it has reached a minimal value. Last, the value of the carrier-envelope phase corresponding to the maximal asymmetry varies with the pulse intensity. This study reveals that the increasing of pulse intensity is helpful for observing the asymmetric photoionization.

The United Kingdom, the United Nations Human Rights Council and the first cycle of the Universal Periodic Review

The introduction of the Universal Periodic Review (UPR) mechanism as an innovative component of the new Human Rights Council in 2006 has suffered little academic scrutiny. This is partly because it holds as its objective an improvement in human rights situations on the ground, a goal that is difficult to test amongst so many possible causal factors attributable to law reform and policy change, and partly due to the fact that the mechanism has only completed one full cycle of review. This article seeks to remedy this absence of analysis by examining the experience of the United Kingdom during its first review. In doing so, the article first considers the conception of the UPR, before progressing to examine the procedure and recommendations made to the UK by its peers. Finally, the article considers the five year review of the UPR which occurred as a subset of the Human Rights Council Review in 2011 and the resulting changes to the process modalities.

Bcl-xL regulation and function in cell cycle checkpoints and progression

Quelques évidences suggèrent que Bcl-xL, un membre anti-apoptotique de la famille Bcl-2, possède également des fonctions au niveau du cycle cellulaire et de ses points-contrôle. Pour étudier la régulation et fonction de Bcl-xL au cours du cycle cellulaire, nous avons généré et exprimé dans des cellules humaines une série de mutants de phosphorylation incluant Thr41Ala, Ser43Ala, Thr47Ala, Ser49Ala, Ser56Ala, Ser62Ala et Thr115Ala. L'analyse de cette série de mutants révèle que les cellules exprimant Bcl-xL(Ser62Ala) sont moins stables au point-contrôle G2 du cycle cellulaire comparées aux cellules exprimant le type sauvage ou les autres mutants de phosphorylation incluant Thr41Ala, Ser43Ala, Thr47Ala, Ser56Ala et Thr115Ala. Les études de cinétiques de phosphorylation et de localisation de phospho-Bcl-xL(Ser62) dans des cellules synchronisées et suite à l'activation du point-contrôle en G2 médié par l'étoposide (VP16), nous indiquent que phospho-Bcl-xL(Ser62) migre dans les corps nucléolaires durant l'arrêt en G2 dans les cellules exposées au VP16. Une série d'expériences incluant des essais kinase in vitro, l'utilisation d'inhibiteurs pharmacologiques et d'ARN interférant, nous révèlent que Polo kinase 1 (PLK1) et MAPK9/JNK2 sont les protéines kinase impliquées dans la phosphorylation de Bcl-xL(Ser62), et pour son accumulation dans les corps nucléolaires pendant le point-contrôle en G2. Nos résultats indiquent que durant le point-contrôle en G2, phospho-Bcl-xL(Ser62) se lie et se co-localise avec CDK1(CDC2), le complexe cycline-kinase qui contrôle l'entrée en mitose. Nos résultats suggèrent que dans les corps nucléolaires, phospho-Bcl-xL(Ser62) stabilise l'arrêt en G2 en séquestrant CDK1(CDC2) pour retarder l'entrée en mitose. Ces résultats soulignent également que les dommages à l'ADN influencent la composition des corps nucléolaires, structure nucléaire qui émerge maintenant comme une composante importante de la réponse aux dommages à l'ADN. Dans une deuxième étude, nous décrivons que les cellules exprimant le mutant de phosphorylation Bcl-xL(Ser62Ala) sont également plus stables au point-contrôle de l'assemblage du fuseau de la chromatine (SAC) suite à une exposition au taxol, comparées aux cellules exprimant le type sauvage ou d'autres mutants de phosphorylation de Bcl-xL, incluant Thr41Ala, Ser43Ala, Thr47Ala, Ser56Ala. Cet effet est indépendent de la fonction anti-apoptotique de Bcl-xL. Bcl-xL(Ser62) est fortement phosphorylé par PLK1 et MAPK14/SAPKp38α à la prométaphase, la métaphase et à la frontière de l'anaphase, et déphosphorylé à la télophase et la cytokinèse. Phospho-Bcl-xL(Ser62) se trouve dans les centrosomes avec γ-tubuline, le long du fuseau mitotique avec la protéine moteure dynéine et dans le cytosol mitotique avec des composantes du SAC. Dans des cellules exposées au taxol, phospho-Bcl-xL(Ser62) se lie au complexe inhibiteur CDC20/MAD2/BUBR1/BUB3, alors que le mutant Bcl-xL(Ser62Ala) ne se lie pas à ce complexe. Ces résultats indiquent que durant le SAC, la phosphorylation de Bcl-xL(Ser62) accélère la résolution du SAC et l'entrée des cellules en anaphase. Des expériences bloquant l'expression de Bcl-xL révèlent ègalement un taux très élevé de cellules tétraploïdes et binuclées après un traitement au nocodazole, consistant avec une fonction de Bcl-xL durant la mitose et dans la stabilité génomique. Dans la troisième étude, l'analyse fonctionnelle de cette série de mutants de phosphorylation indique également que les cellules exprimant Bcl-xL(Ser49Ala) sont moins stables durant le point-contrôle G2 et entre en cytokinèse plus lentement dans des cellules exposées aux inhibiteurs de la polymérisation/dépolymérisation des tubulines, composantes des microtubules. Ces effets de Bcl-xL(Ser49Ala) sont indépendents de sa fonction anti-apoptotique. La phosphorylation de Bcl-xL(Ser49) est dynamique au cours du cycle cellulaire. Dans des cellules synchronisées, Bcl-xL(Ser49) est phosphorylé en phase S et G2, déphosphorylé à la prométaphase, la métaphase et à la frontière de l'anaphase, et re-phosphorylé durant la télophase et la cytokinèse. Au cours du point-contrôle G2 induit par les dommages à l'ADN, un pool important de phospho-Bcl-xL(Ser49) se trouve aux centrosomes, un site important pour la régulation de l'entrée en mitose. Durant la télophase et la cytokinèse, phospho-Bcl-xL(Ser49) se trouve le long des microtubules avec la protéine moteure dynéine et dans le cytosol mitotique. Finalement, nos résultats suggèrent que PLK3 est responsable de la phosphorylation de Bcl-xL(Ser49), une protéine kinase impliquée pour l'entrée des cellules en mitose et pour la progression de la mitose jusqu'à la division cellulaire.

Engaging Students in the Implementation of Criterion Referenced Assessment in First Year Law

The Queensland University of Technology (QUT) University Academic Board approved a new QUT Assessment Policy in September 2003, which requires a criterion-referenced approach as opposed to a norm-referenced approach to assessment across the university(QUT,MOPP,2003). In 2004, the QUT Law School embarked upon a process of awareness raising about criterion-referenced assessment amongst staff and from 2004 – 2005 staggered the implementation of criterion-referenced assessment in all first year core undergraduate law units. This paper will briefly discuss the benefits and potential pitfalls of criterion referenced assessment and the context for implementing it in the first year law program, report on student’s feedback on the introduction of criterion referenced assessment and the strategies adopted in 2005 to engage students more fully in criterion referenced assessment processes to enhance their learning outcomes.

Integrating health and sustainability in life cycle assessment

Until now health impact assessment and environmental impact assessment are two different issues, often not addressed together. Both issues have to be dealt with for sustainable building. The aim of this paper is to link healthy and sustainable housing in life cycle assessment. Two strategies are studied: clean air as a functional unity and health as a quality indicator. The strategies are illustrated with an example on the basis of Eco-Quantum, which is a Dutch whole-building assessment tool. It turns out that both strategies do not conflict with the LCA methodology. The LCA methodology has to be refined for this purpose.