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1
Bonfrate, Anthony. "Développement d'un modèle analytique dédié au calcul des doses secondaires neutroniques aux organes sains des patients en protonthérapie." Thesis, Université Paris-Saclay (ComUE), 2016. http://www.theses.fr/2016SACLS408/document.
Full textAbstract:
Les doses secondaires neutroniques ne sont actuellement pas estimées lors de la planification de traitement dans les centres de protonthérapie puisque les logiciels de planification de traitement (TPS) ne le proposent pas tandis que les simulations Monte Carlo (MC) et les mesures sont inadaptées pour un environnement clinique. L’objectif de la thèse est de développer un modèle analytique dédié à l’estimation des doses secondaires neutroniques aux organes sains qui reste pratique et simple d’utilisation en routine clinique. Dans un premier temps, la géométrie existante de la gantry installée au Centre de protonthérapie d’Orsay (CPO) de l’institut Curie modélisée avec le code de calcul MCNPX a été étendue à trois configurations de traitement supplémentaires (énergie en entrée de ligne de 162, 192 et 220 MeV). Une approche comparative simulation-mesure a ensuite été entreprise afin de vérifier la capacité de ces modélisations à reproduire les distributions de doses (en profondeur et latérales) des protons primaires ainsi que le champ secondaire neutronique. Des écarts inférieurs à 2 mm ont été observés pour les protons primaires. Pour les neutrons secondaires, les écarts sont plus mitigés avec des rapports simulation sur mesure de ~2 et de ~6, respectivement pour la spectrométrie et les équivalents de dose dans un fantôme physique. L’analyse des résultats a permis d’identifier l’origine de ces écarts et de mettre en perspective la nécessité de conduire de nouvelles études pour améliorer à la fois les mesures expérimentales et les simulations MC. Dans un deuxième temps, une approche purement numérique a été considérée pour calculer les doses neutroniques aux organes sains de fantômes voxélisés représentant des patients d’un an, de dix ans et adulte, traités pour un craniopharyngiome. Une variation de chaque paramètre de traitement a été réalisée afin d’étudier leur influence respective sur les doses neutroniques. Ces paramètres ont pu être ordonnés par ordre décroissant d’influence : incidence de traitement, distance organe-collimateur et organe-champ de traitement, taille/âge des patients, énergie de traitement, largeur de modulation, ouverture du collimateur, etc. Des suggestions ont également été avancées pour réduire les doses neutroniques.Dans un troisième temps, un modèle analytique a été conçu de façon à être utilisable en routine clinique, pour tous les types de tumeur et toutes les installations de protonthérapie. Son entraînement séparé pour trois incidences de traitement a montré des écarts inferieurs à ~30% et ~60 µGy Gy⁻¹ entre les données d’apprentissage (doses neutroniques calculées aux organes sains) et les valeurs prédites par le modèle analytique. La validation a consisté à comparer les doses neutroniques estimées par le modèle analytique à celles calculées avec MCNPX pour des conditions différentes des données d’apprentissage. Globalement, un accord acceptable a été observé avec des écarts moyens de ~30% et ~100 µGy Gy⁻¹. La flexibilité et la fiabilité du modèle analytique ont ainsi été mises en évidence. L’entraînement du modèle analytique à partir d’équivalents de dose neutroniques mesurés dans un fantôme solide au Centre Antoine Lacassagne a confirmé son universalité, bien qu’il requière néanmoins quelques ajustements supplémentaires pour améliorer sa précisionStray neutron doses are currently not evaluated during treatment planning within proton therapy centers since treatment planning systems (TPS) do not allow this feature while Monte Carlo (MC) simulations and measurements are unsuitable for routine practice. The PhD aims at developing an analytical model dedicated to the estimation of stray neutron doses to healthy organs which remains easy-to-use in clinical routine. First, the existing MCNPX model of the gantry installed at the Curie institute - proton therapy center of Orsay (CPO) was extended to three additional treatment configurations (energy at the beam line entrance of 162, 192 and 220 MeV). Then, the comparison of simulations and measurements was carried out to verify the ability of the MC model to reproduce primary proton dose distributions (in depth and lateral) as well as the stray neutron field. Errors within 2 mm were observed for primary protons. For stray neutrons, simulations overestimated measurements by up to a factor of ~2 and ~6 for spectrometry and dose equivalent in a solid phantom, respectively. The result analysis enabled to identify the source of these errors and to put into perspective new studies in order to improve both experimental measurements and MC simulations. Secondly, MC simulations were used to calculate neutron doses to healthy organs of a one-year-old, a ten-year-old and an adult voxelized phantoms, treated for a carniopharyngioma. Treatment parameters were individually varied to study their respective influence on neutron doses. Parameters in decreasing order of influence are: beam incidence, organ-to-collimator and organ-to-treatment field distances, patient’ size/age, treatment energy, modulation width, collimator aperture, etc. Based on these calculations, recommendations were given to reduce neutron doses. Thirdly, an analytical model was developed complying with a use in clinical routine, for all tumor localizations and proton therapy facilities. The model was trained to reproduce calculated neutron doses to healthy organs and showed errors within ~30% and ~60 µGy Gy⁻¹ between learning data and predicted values; this was separately done for each beam incidence. Next, the analytical model was validated against neutron dose calculations not considered during the training step. Overall, satisfactory errors were observed within ~30% and ~100 µGy Gy⁻¹. This highlighted the flexibility and reliability of the analytical model. Finally, the training of the analytical model made using neutron dose equivalent measured in a solid phantom at the center Antoine Lacassagne confirmed its universality while also indicating that additional modifications are required to enhance its accuracy
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Bessières, Igor. "Développement et validation expérimentale d'un outil de détermination de la dose hors-champ en radiothérapie." Phd thesis, Université Paris Sud - Paris XI, 2013. http://tel.archives-ouvertes.fr/tel-00801314.
Full textAbstract:
Depuis deux décennies, les nombreux développements des techniques de radiothérapie par modulation d'intensité (RCMI) ont permis de mieux conformer la dose au volume cible et ainsi, d'augmenter les taux de réussite des traitements des cancers. Ces techniques ont souvent l'avantage de réduire la dose aux organes à risque proches de la zone traitée, mais elles ont l'inconvénient d'apporter un niveau de dose périphérique plus important que les techniques basiques sans modulation d'intensité. Dans ce contexte, l'augmentation du taux de survie des patients qui en résulte, accroît également la probabilité de manifestation d'effets iatrogènes dus aux doses périphériques (tels que les cancers secondaires). Aujourd'hui, la dose périphérique n'est pas considérée lors de la planification du traitement et il n'existe aucun outil numérique fiable pour sa prédiction. Il devient cependant indispensable de prendre en compte le dépôt de dose périphérique lors de la planification du traitement, notamment dans les cas pédiatriques. Cette étude doctorale a permis la réalisation de plusieurs étapes du développement d'un outil numérique, précis et rapide, de prédiction de la dose hors-champ fondé sur le code Monte Carlo PENELOPE. Dans cet objectif, nous avons démontré la capacité du code PENELOPE à estimer la dose périphérique en comparant ses résultats avec des mesures de référence réalisées à partir de deux configurations expérimentales (métrologique et pré-clinique). Ces travaux expérimentaux ont notamment permis la mise en place d'un protocole d'utilisation des dosimètres OSL pour la mesure des faibles doses. En parallèle, nous avons pu mettre en évidence la convergence lente et rédhibitoire du calcul en vue d'une utilisation clinique. Par conséquent nous avons réalisé un travail d'accélération du code en implémentant une nouvelle technique de réduction de variance appelée transport pseudo-déterministe spécifiquement dédiée à l'amélioration de la convergence dans des zones lointaines du faisceau principal. Ces travaux ont permis d'améliorer l'efficacité des estimations dans les deux configurations de validation définies (gain d'un facteur 20) pour atteindre des temps de calcul raisonnables pour une application clinique. Des travaux d'optimisation du code restent à entreprendre de façon à améliorer encore la convergence de l'outil pour ensuite en envisager une utilisation clinique.
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Bessières, Igor. "Développement et validation expérimentale d’un outil de détermination de la dose hors-champ en radiothérapie." Thesis, Paris 11, 2013. http://www.theses.fr/2013PA112016/document.
Full textAbstract:
Depuis deux décennies, les nombreux développements des techniques de radiothérapie par modulation d’intensité (RCMI) ont permis de mieux conformer la dose au volume cible et ainsi, d’augmenter les taux de réussite des traitements des cancers. Ces techniques ont souvent l’avantage de réduire la dose aux organes à risque proches de la zone traitée, mais elles ont l’inconvénient d’apporter un niveau de dose périphérique plus important que les techniques basiques sans modulation d’intensité. Dans ce contexte, l’augmentation du taux de survie des patients qui en résulte, accroît également la probabilité de manifestation d’effets iatrogènes dus aux doses périphériques (tels que les cancers secondaires). Aujourd’hui, la dose périphérique n’est pas considérée lors de la planification du traitement et il n’existe aucun outil numérique fiable pour sa prédiction. Il devient cependant indispensable de prendre en compte le dépôt de dose périphérique lors de la planification du traitement, notamment dans les cas pédiatriques. Cette étude doctorale a permis la réalisation de plusieurs étapes du développement d’un outil numérique, précis et rapide, de prédiction de la dose hors-champ fondé sur le code Monte Carlo PENELOPE. Dans cet objectif, nous avons démontré la capacité du code PENELOPE à estimer la dose périphérique en comparant ses résultats avec des mesures de référence réalisées à partir de deux configurations expérimentales (métrologique et pré-clinique). Ces travaux expérimentaux ont notamment permis la mise en place d’un protocole d’utilisation des dosimètres OSL pour la mesure des faibles doses. En parallèle, nous avons pu mettre en évidence la convergence lente et rédhibitoire du calcul en vue d’une utilisation clinique. Par conséquent nous avons réalisé un travail d’accélération du code en implémentant une nouvelle technique de réduction de variance appelée transport pseudo-déterministe spécifiquement dédiée à l’amélioration de la convergence dans des zones lointaines du faisceau principal. Ces travaux ont permis d’améliorer l’efficacité des estimations dans les deux configurations de validation définies (gain d’un facteur 20) pour atteindre des temps de calcul raisonnables pour une application clinique. Des travaux d’optimisation du code restent à entreprendre de façon à améliorer encore la convergence de l’outil pour ensuite en envisager une utilisation cliniqueOver the last two decades, many technical developments have been achieved on intensity modulated radiotherapy (IMRT) and allow a better conformation of the dose to the tumor and consequently increase the success of cancer treatments. These techniques often reduce the dose to organs at risk close to the target volume; nevertheless they increase peripheral dose levels. In this situation, the rising of the survival rate also increases the probability of secondary effects expression caused by peripheral dose deposition (second cancers for instance). Nowadays, the peripheral dose is not taken into account during the treatment planification and no reliable prediction tool exists. However it becomes crucial to consider the peripheral dose during the planification, especially for pediatric cases. Many steps of the development of an accurate and fast Monte Carlo out-of-field dose prediction tool based on the PENELOPE code have been achieved during this PhD work. To this end, we demonstrated the ability of the PENELOPE code to estimate the peripheral dose by comparing its results with reference measurements performed on two experimental configurations (metrological and pre-clinical). During this experimental work, we defined a protocol for low doses measurement with OSL dosimeters. In parallel, we highlighted the slow convergence of the code for clinical use. Consequently, we accelerated the code by implementing a new variance reduction technique called pseudo-deterministic transport which is specifically with the objective of improving calculations in areas far away from the beam. This step improved the efficiency of the peripheral doses estimation in both validation configurations (by a factor of 20) in order to reach reasonable computing times for clinical application. Optimization works must be realized in order improve the convergence of our tool and consider a final clinical use
4
Ronga, Maria Grazia. "Study and modelling of very high energy electrons (VHEE) radiation therapy." Electronic Thesis or Diss., université Paris-Saclay, 2024. http://www.theses.fr/2024UPAST036.
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Le développement de méthodes innovantes susceptibles de réduire la sensibilité des tissus sains aux radiations, tout en maintenant l'efficacité du traitement sur la tumeur, est un aspect central de l'amélioration de l'efficacité de la radiothérapie pour le traitement du cancer. Parmi les développements et innovations méthodologiques possibles, la combinaison d'une irradiation à ultra-haut débit de dose (FLASH) et d'électrons de très haute énergie (VHEE) pourrait permettre d'exploiter les avantages radiobiologiques de l'effet FLASH pour le traitement des tumeurs profondes. En particulier, les VHEEs dans la gamme d'énergie de 100 à 250 MeV seraient particulièrement intéressants d'un point de vue balistique et biologique pour l'application des irradiations FLASH en radiothérapie. Cette thèse étudie donc l'utilisation possible des VHEEs en radiothérapie et en particulier leur utilisation à ultra-haut débit de dose, évaluant ainsi la faisabilité de la radiothérapie FLASH-VHEE. Bien que prometteuse, plusieurs aspects de cette technique doivent être étudiés avant qu'elle puisse être employée dans un contexte clinique. Une première partie du travail étudie les paramètres de la machine nécessaires pour répondre aux contraintes des irradiations FLASH. À cette fin, un modèle analytique de calcul de la dose basé sur la théorie de la diffusion multiple de Fermi-Eyges a été développé et testé. Ce modèle analytique a également été utilisé pour concevoir et optimiser un système de double diffusion pour la thérapie VHEE et ainsi obtenir des tailles de champ supérieures à 15x15 cm², et pour évaluer la possible adaptation des méthodes de conformation conventionnelles du faisceau de particules pour la thérapie FLASH-VHEE. La deuxième partie de ce travail porte sur la planification du traitement par VHEE et l'évaluation des plans cliniques. Quatre cas cliniques représentatifs ont été étudiés, pour lesquels des plans de traitement par balayage de mini-faisceau (PBS) et par double diffusion (DS) ont été calculés. L'influence de l'énergie du faisceau sur la qualité du plan a été étudiée et les techniques PBS et DS ont été comparées. Une description temporelle de l'irradiation a également été réalisée ainsi que l'incorporation d'un facteur de modification FLASH lors de l'évaluation du plan et de son effet sur les tissus sains en mode FLASH. Enfin, l'estimation des doses liées aux particules secondaires et les questions de radioprotection ont été abordées. Un calcul de la dose secondaire due aux photons de Bremsstrahlung et aux neutrons provenant des deux systèmes de délivrance de la dose a été développé dans l'eau. La dose dues aux particules secondaires reçues par divers organes a également été évaluée dans le cadre de traitements intracrâniens et afin de démontrer l'avantage des faisceaux VHEE par rapport aux faisceaux de protons en terme de dose neutrons hors champ. En résumé, les modèles analytiques accélérés et paramétrés dans cette étude permettent une estimation de la distribution de la dose produite par un système VHEE avec une bonne précision, ce qui fournit des informations importantes pour la conception éventuelle d'un système VHEE. Les résultats de ce travail pourraient soutenir le développement de la radiothérapie FLASH-VHEEThe development of innovative methods capable of reducing the sensitivity of healthy tissue to radiation, while maintaining the effectiveness of the treatment on the tumour, is a central aspect of improving the effectiveness of radiotherapy in the treatment of cancer. Among possible developments and methodological innovations, the combination of ultra-high dose rate irradiation (FLASH) and very high energy electrons (VHEE) could make it possible to exploit the radiobiological advantages of the FLASH effect for the treatment of deep tumours. In particular, VHEEs in the 100 to 250 MeV energy range would be particularly interesting from a ballistic and biological point of view for the application of FLASH irradiation in radiotherapy. This thesis therefore studies the possible use of VHEEs in radiotherapy, and in particular their use at ultra-high dose rates, thus assessing the feasibility of FLASH-VHEE radiotherapy. Although promising, several aspects of this technique need to be studied before it can be used in a clinical context. The first part of this work studies the machine parameters required to meet the constraints of FLASH irradiation. To this end, an analytical model for calculating the dose based on Fermi-Eyges multiple scattering theory was developed and tested. This analytical model has also been used to design and optimise a double-scattering system for VHEE therapy, in order to obtain field sizes greater than 15x15 cm², and to assess the possible adaptation of conventional particle beam conformation methods for FLASH-VHEE therapy. The second part of this work focuses on VHEE treatment planning and the evaluation of clinical plans. Four representative clinical cases were studied, for which pencil-beam scanning (PBS) and double scattering (DS) treatment plans were calculated. The influence of beam energy on plan quality was studied and the PBS and DS techniques were compared. A temporal description of the irradiation was also carried out, as well as the incorporation of a FLASH modification factor when evaluating the plan and its effect on healthy tissue in FLASH mode. Finally, the estimation of doses from secondary particles and radiation protection issues were addressed. A calculation of the secondary dose due to Bremsstrahlung photons and neutrons from the two dose delivery systems was developed in water. The secondary particle dose received by various organs was also assessed in the context of intracranial treatments and in order to demonstrate the advantage of VHEE beams over proton beams in terms of out-of-field neutron dose. In summary, the fast analytical models parameterised in this study allow the dose distribution produced by a VHEE system to be estimated with good accuracy, providing important information for the potential design of a VHEE system. The results of this work could support the development of FLASH-VHEE radiotherapy
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Hourcade-Potelleret, Florence. "De la dose à l'effet clinique : utilisation de la modélisation dans les différentes étapes du processus de prédiction du critère clinique : Exemple avec un nouveau médicament en prévention secondaire de la morbidité-mortalité cardiovasculaire." Phd thesis, Université Jean Monnet - Saint-Etienne, 2012. http://tel.archives-ouvertes.fr/tel-00979667.
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Les données épidémiologiques montrent une association inverse entre les taux de HDL-cholestérol (HDL-C) et le risque d'évènements cardiovasculaires. Des traitements ayant montré une augmentation significative du HDL-C, comme les inhibiteurs de la protéine de transfert des esters de cholestérol, devraient donc permettre de réduire le risque cardio-vasculaire. En utilisant différentes techniques de modélisation, nous avons tenté de quantifier l'efficacité attendue sur les événements cardiovasculaires de l'un d'entre eux, le dalcétrapib, ne disposant que de données pharmacocinétiques et pharmacodynamiques. Tout d'abord, afin d'établir la relation pharmacocinétique / pharmacodynamique entre les concentrations et la modification de HDL-C, nous avons analysé les données individuelles des patients dyslipidémiques par une approche de population. Une hausse moyenne de HDL-C de 26.4 % par rapport au placebo était alors anticipée. Nous avons ensuite tenté de corréler l'effet observé sur l'HDL-C et l'effet clinique à partir de données d'autres études par méta-régression des essais évaluant l'effet des principaux hypolipémiants en prévention secondaire. Cette modélisation n'a pas permis de montrer de corrélation entre le changement de l'HDL-C (P5 P95 :-3.0 et 36 %) et la réduction du risque cardiovasculaire. Une analyse de sensibilité par type de traitement suggère qu'une même hausse de HDL-C entre deux classes thérapeutiques pourrait se traduire par un effet clinique dissemblable, indiquant que HDL-C ne peut pas être utilisé comme critère intermédiaire puisqu'il ne serait pas un prédicteur indépendant du risque cardiovasculaire
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Ryckman, Jeffrey M. "Using MCNPX to calculate primary and secondary dose in proton therapy." Thesis, Georgia Institute of Technology, 2011. http://hdl.handle.net/1853/39499.
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Proton therapy is a relatively new treatment modality for cancer, having recently been incorporated into hospitals in the last two decades. Although proton therapy has much higher start up and treatment costs than traditional methods of radiotherapy, it continues to expand in use today. One reason for this is that proton therapy has the advantage of a more precise localization of dose compared to traditional radiotherapy. Other proposed advantages of proton therapy in the treatment of cancer may lead to a faster expanse in its use if proven to be more effective than traditional radiotherapy. Therefore, much research must be done to investigate the possible negative and positive effects of using proton therapy as a treatment modality.
In proton therapy, protons do account for the vast majority of dose. However, when protons travel through matter, secondary particles are created by the interactions of protons and matter en route to and within the patient. It is believed that secondary dose can lead to secondary cancer, especially in pediatric cases. Therefore, the focus of this work is determining both primary and secondary dose.
In order to develop relevant simulations, the specifications of the treatment room and beam were based off of real-world facilities as closely as possible. Using available data from proton accelerators and clinical facilities, an accurate proton therapy nozzle was designed. Dose calculations were performed by MCNPX using a simple water phantom, and then beam characteristics were investigated to ensure the accuracy of the model. After validation of the beam nozzle, primary and secondary dose values were tabulated and discussed. By demonstrating the method of these calculations, the purpose of this work is to serve as a guide into the relatively recent field of Monte Carlo methods in proton therapy.
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Fricker, Katherine. "Collateral exposure: the additional dose from radiation treatment." Thesis, University of Canterbury. Physics and Astronomy, 2012. http://hdl.handle.net/10092/10361.
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For patients receiving radiation therapy, there is a risk of developing radiation induced carcinomas, especially if they have a long life expectancy. However, radiotherapy is not the only contributor of radiation exposure to healthy tissue. With the introduction of highly conformal treatment techniques comes the increase in pretreatment imaging necessary to accurately target tumour volumes and consequently, radiation exposure to healthy tissue.
In this work the radiation dose delivered to radiosensitive organs from a number of treatment planning techniques was evaluated and the risk of radiation induced cancer was assessed. MOSFET detectors and Gafchromic film were used to measure the accumulative concomitant dose to the thyroid and contralateral breast from early stage breast carcinoma
radiotherapy and to the contralateral testis from seminoma radiotherapy, with dose contributions from CT imaging for treatment planning, pretreatment imaging (CBCT) and treatment
delivery peripheral dose. To the author's knowledge this is the first work investigating the total concomitant treatment related dose and associated risk to these treatment sites.
Peripheral dose contributed the largest concomitant dose to the healthy tissue, measuring up to 0.7, 1.0 and 5.0 Gy to the testis, thyroid and contralateral breast, respectively. The
highest testicular, thyroid and contralateral breast carcinoma risk was found to be 0.4, 0.2 and 1.4%, respectively.
In conclusion, the risk of radiation induced carcinoma to the assessed radiosensitive tissues was found to be minimal, however, when considering treatment techniques and/or
introducing pretreatment imaging protocols, the dose to the normal tissue should be kept as low as reasonably achievable.
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Leitão, João Luís Vieira. "Climate changes: effects of secondary salinisation in freshwater organisms." Master's thesis, Universidade de Aveiro, 2011. http://hdl.handle.net/10773/8332.
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Mestrado em Biologia AplicadaAs global climate patterns change, so will freshwater availability. Specially, salinisation of freshwater costal ecosystem is a major point of concern; either by surface flooding or by groundwater intrusions of seawater. This may be potentiated by the decrease of freshwater availability provoked by longer drought periods, evaporation, and increased freshwater extraction (for example for agriculture and other human uses). According, the present work aimed at evaluating how freshwater organisms responded to an increase in salinity. To achieve this main objective two specific goals were delineated: (i) to compare the toxicity of seawater with a surrogate (NaCl), commonly used in laboratory toxicity assays, to two standard freshwater species, and (ii) to assess if an association exist between resistance to chemical contamination and to increased salinity; since many populations, predicted to experience future increased salinity, are presently exposed to chemical contamination. To accomplish the first objective the sensitivity of the green algae Pseudokirchneriella subcapitata (Korshikov) F. Hindák and of the cladoceran Daphnia magna Straus to NaCl and to natural seawater was evaluated. Growth rate for P. subcapitata, and mortality, time to release the first brood, body size, total reproduction, and intrinsic rate of natural increase for D. magna, were monitored after exposing these species to two series of solutions with an increasing gradient of salinity. One series of solutions was established with a natural seawater sample and the other with NaCl dissolved artificial media. To address the second objective, four cloned lineages of Daphnia longispina O.F. Müller, exhibiting different sensitivities to lethal levels of copper, were exposed to a gradient of lethal and sublethal levels of salinity, established with the salt NaCl. The same endpoins described for D. magna were also monitored for D. longispina. The obtained results showed that NaCl exerted a higher toxicity to P. subcapitata (LOEC of 5.9mS/cm and 9.6mS/cm, respectively for NaCl and seawater) and to D. magna (LC50,48h of 9.88mS/cm and 11.32mS/cm; and EC50 for total reproduction of 8.9mS/cm and 10.4mS/cm, respectively for NaCl and seawater) than the natural seawater. These data suggest that the use of NaCl as a surrogate for seawater to predict, in laboratory, the effects of seawater intrusion in freshwater is a protective approach as it simulates a “Worst Case Scenario” of exposure. An association between resistance to copper and to NaCl was not observed for the tested cloned lineages of D. longispina (r < 0.92 and p > 0.08), though the two clonal lineages most resistant to copper also exhibited the highest sensitivity to sublethal levels of NaCl (determined as the EC20 for total reproduction). Finally, obtained data demonstrated that D. longispina was more sensitive to increased salinity (LC50,48h of 2.85g/L to 2.48g/L or, conductivity values of LC50,48h of 5.50mS/cm to LC50,48h= 4.57mS/cm which correspond respectively to the highest and lowest recorded values in these assays) than the standard species (D. magna), highlighting the importance of using autochthonous species for the ecological risk assessment of secondary salinisation.
À medida que os padrões climáticos se alteram também a disponibilidade de água doce se irá alterar. Como tal, a salinização de ecossistemas costeiros, principalmente os dulçaquicolas, torna-se um ponto de preocupação fundamental. Quer devido ao aumento de intrusões de água do mar por inundação ou por intrusões salinas através dos lençóis freáticos, quer devido à diminuição de entrada de água doce, provocada por períodos mais prolongados de seca, evaporação e aumento do uso de água para actividades antropogénicas. De acordo com o exposto, o presente trabalho pretendeu avaliar as respostas de organismos dulçaquicolas a alterações provocadas pelo aumento de salinidade. Para atingir este objectivo principal foram delineados dois objectivos específicos: (i) comparar a toxicidade de água do mar com a do sal NaCl, comummente usado em laboratório como substituto de água do mar e (ii) averiguar uma possível correlação entre a resistência a contaminação química (cobre) e a aumento de salinidade; uma vez que muitas das populações que se prevê virem a ser afectadas por salinização estão, presentemente, já expostas a contaminação química. Para abordar o primeiro objectivo, a alga verde Pseudokirchneriella subcapitata (Korshikov) F. Hindák e o cladócero Daphnia magna Straus foram expostos a dois gradientes crescentes de salinidade estabelecidos com água do mar natural e com NaCl dissolvido num meio artificial.. No ensaio com a alga verde unicelular foi avaliada a inibição do crescimento; no ensaio com D. magna foram avaliados os seguintes parâmetros: mortalidade, tempo decorrido até libertar a primeira ninhada, comprimento corporal, reprodução total, taxa de crescimento intrínseco. Para atingir o segundo objectivo, foram seleccionadas quatro linhagens do cladócero Daphnia longispina O.F Müller com sensibilidades diferentes a níveis letais de cobre. As quatro linhagens foram expostas a um gradiente de concentrações, letais e sub-letais, de NaCl. Neste ensaio foram analisados os mesmo parâmetros descritos anteriormente para o ensaio com D. magna. Os resultados demonstram que o sal NaCl apresentou maior toxicidade do que a água do mar natural, quer para P. subcapitata (LOEC de 5.9mS/cm e de 9.6mS/cm, respectivamente para NaCl e água do mar), quer para D. magna (LC50,48h de 9.88mS/cm e LC50,48h= 11.32mS/cm; e EC50, para reprodução total, de 8.9mS/cm e 10.4mS/cm, respectivamente para NaCl e água do mar). Estes dados sugerem que o uso de NaCl, em laboratório, como um substituto de água do mar deve ser considerado como uma abordagem protectora, uma vez que simula um cenário de maior toxicidade. Não foi observada uma associação significativa entre maior resistência a cobre e a NaCl nas linhagens de D. longispina testadas (r < 0.92 and p ≥ 0.08), apesar de as duas linhagens mais resistentes a cobre apresentarem as maiores sensibilidades a níveis subletais (para reprodução total) de NaCl. Finalmente, os dados obtidos demonstram que D. longispina é mais sensível ao aumento de salinidade (o intervalo de valores de LC50,48h calculados foi de 2.85g/l a 2.48g/l de NaCl, correspondente a valores de conductividade de 5.50mS/cm e 4.57mS/cm, respectivamente) que a espécie padrão (D. magna), salientando a importância do uso de espécies autóctones na avaliação de risco ecológico em situações de intrusões salinas.
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Jaillet, Cyprien. "Modifications du glycome endothélial vasculaire dans le contexte d'une irradiation à forte dose." Thesis, Paris 6, 2017. http://www.theses.fr/2017PA066021/document.
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La radiothérapie constitue l’un des principaux traitements pour l’éradication des cancers. Cependant, elle présente un risque d’effets secondaires aux tissus sains environnant la tumeur. Dans ce processus, le système vasculaire et plus particulièrement l’endothélium jouent un rôle clé. Les cellules endothéliales activées favorisent le recrutement chronique des thrombocytes et des leucocytes, contribuant ainsi aux effets secondaires. D’autre part, dans les maladies inflammatoires, les glycanes exprimés à la surface des cellules endothéliales sont modifiés et influencent le recrutement des cellules immunitaires. Dans cette étude, nous avons évalué la modification des glycanes endothéliaux en réponse à une irradiation à forte dose, et étudié les effets fonctionnels de ces modifications sur le recrutement des leucocytes en utilisant un modèle de cellules endothéliales (HUVECs) in vitro. Nos résultats apportent les premières preuves d’une modification du glycome des cellules endothéliales en réponse à l’irradiation. Les N-glycanes hautement mannosylés, les O-glycanes et les motifs sialylées sont surexprimés. Parallèlement, le glycocalyx endothélial semble subir une dégradation. Nous avons évalué l’effet fonctionnel des modifications glycanique des cellules endothéliales irradiées sur l’adhésion d’une lignée de monocyte (THP-1). Nos résultats montrent que l’adhésion radio-induite est en partie due à la surexpression endothéliale des N-glycanes hautement mannosylés. Nous avons aussi évalué le glycome sur un modèle de souris irradiées et sur des pièces opératoires de patients traités par radiothérapies. Nos résultats de transcriptomiques sur la souris suggèrent l’existence de modifications glycaniques radio-induites in vivo. L’intégration de la composante glycanique permet de porter un regard nouveau sur le continuum d’évènement qui conduit aux lésions tissulaires radio-induites. A l’avenir, l’étude du glycome pourrait ouvrir de nouvelles pistes thérapeutiques pour une meilleure prise en charge des effets secondaires de la radiothérapieRadiotherapy is one of the main treatments against cancers. However, it presents a risk of adverse effects for the normal tissues surrounding the tumors. The vascular network and especially the endothelium are considered as main targets to limit normal tissue damages and prevent side effects of radiotherapy. Activated endothelial cells are involved in the chronic recruitment of thrombocytes and leukocytes, resulting in tissue complications. On the other hand, in inflammatory diseases, the glycans expressed on the surface of endothelial cells are modified and lead to immune cells recruitment. We sought to evaluate changes in endothelial glycome in a context of exposure to high dose of radiation, and studied the functional consequences on the recruitment of leukocytes. In vitro, the characterization of the glycome was performed on a primary endothelial cell model (HUVEC). Our results provide the first evidences of an endothelial modification of the glycome after exposure to ionizing radiation. We report an overexpression of high mannose N-glycans, O-glycans and syalilated motifs. At the same time, endothelial glycocalyx appeared to be damaged by exposure to radiation. Next, we evaluated these radiation-induced modifications of endothelial glycans on monocyte adhesion. We show that the radiation induced adhesion was mediated by overexpression of high mannose N-glycans. We also investigated changes in glycome in an irradiated mouse model of enteropathy and in resections of patients treated with radiotherapy. In mice, a transcriptomic study suggests changes in glycans following radiation exposure. Collectively, these findings on glycome changes provide a new perspective of the continuum of events leading to normal tissue complications. In the future, the study of the glycome should open new therapeutics opportunities for better management of tissue damages induced by radiation
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Borucki, Suzanne Janette. "Parent involvement at the secondary level? It can be done!" CSUSB ScholarWorks, 1998. https://scholarworks.lib.csusb.edu/etd-project/1665.
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Sayah, Rima. "Evaluations des doses dues aux neutrons secondaires reçues par des patients de différents âges traités par protonthérapie pour des tumeurs intracrâniennes." Phd thesis, Université Paris Sud - Paris XI, 2012. http://tel.archives-ouvertes.fr/tel-00810289.
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La protonthérapie est une technique avancée de radiothérapie qui permet de délivrer une dose élevée à la tumeur, tout en épargnant au mieux les tissus sains environnants, grâce aux propriétés balistiques des protons. Cependant, des particules secondaires, principalement des neutrons, sont créées par les interactions nucléaires que les protons initient dans les composantes de la ligne et de la salle de traitement, ainsi que dans le patient. Ces neutrons secondaires conduisent à des doses indésirables déposées aux tissus sains situés à distance du volume cible, dont la conséquence pourrait être une augmentation du risque de développement de seconds cancers chez les patients traités et en particulier chez les enfants. Cette thèse a pour objectif d'évaluer par calcul les doses dues aux neutrons secondaires reçues par des patients de différents âges traités à l'Institut Curie- centre de protonthérapie d'Orsay (ICPO) par des faisceaux de protons de 178 MeV pour des tumeurs intracrâniennes. Les traitements sont réalisés dans la nouvelle salle de l'ICPO équipée d'un bras isocentrique IBA. Les composants de la ligne et de la salle de traitement ainsi que la source de protons ont été modélisés à l'aide du code de calcul Monte Carlo MCNPX. Le modèle obtenu a été validé par une série de comparaisons de calculs à des mesures expérimentales. Ces comparaisons ont concerné : a) les distributions de doses latérales et en profondeur du faisceau de protons primaire dans un fantôme d'eau, b) la spectrométrie des neutrons en une point de la salle, c) les équivalents de doses ambiants en différents points de la salle et d) les doses à distance du volume cible au sein d'un fantôme physique anthropomorhe. Des accords satisfaisants ont été obtenus entre les calculs et les mesures, permettant ainsi de considérer le modèle comme validé.Les fantômes hybrides-voxels de différents âges, développés par l'Université de Floride ont été ensuite introduits dans le modèle et des calculs de doses dues aux neutrons secondaires aux différents organes de ces fantômes ont été réalisés. Les doses diminuent lorsque la distance de l'organe au champ de traitement augmente et lorsque l'âge du patient augmente. Un patient de 1 an peut recevoir des doses deux fois plus élevées qu'un adulte. La dose maximale, égale à 16,5 mGy pour un traitement délivrant 54 Gy à la tumeur, est reçue, pour le fantôme de 1 an, par les glandes salivaires. Une incidence latérale (gauche ou droite) du faisceau de protons peut délivrer des doses deux fois plus élevées qu'une incidence supérieure (gauche ou droite), et quatre fois plus élevées qu'une incidence antéro-supérieure pour certains organes. Des doses équivalentes aux organes dues aux neutrons ont été aussi calculées. Les facteurs de pondération wR des neutrons varient entre 4 et 10, et les doses équivalentes atteignent au maximum 155 mSv au cours d'un traitement complet.
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Wilson, G. Stuart. "Understanding what needs to be done to improve a school." Thesis, Brunel University, 2003. http://bura.brunel.ac.uk/handle/2438/5525.
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The purpose of this research is to discover different ways of understanding what needs to be done to improve a school, with particular reference to secondary school head teachers. The variation within those understandings, and how the understandings are logically and hierarchically related, are also of interest. Contributions of theory and knowledge to the quality of head teachers' thinking, in terms of negotiating personal and collective meanings, and implying interventions based on interpretations, are suggested. It is argued that the place of thinking (feeling and awareness) within school improvement is supreme, as thinking determines action, and we can only act in relation to how we perceive, experience, or understand a situation. The relevant literature offers indicators of effective schools, helpful descriptors for aspects of the school improvement processes, suggestions for leadership actions, examples of expert practitioners, and a wide spectrum of theories of organisations and education management. What it does not consider is how this knowledge might combine and interact with experience to form different ways of understanding what needs to be done to improve a school. This research addresses the identified gap in the literature, and deepens our knowledge of the inner aspects of school improvement for both theorist and reflective practitioner. The distinct understandings are derived from two sources, a range of literature that can be related to school improvement, and some empirical research consisting of a simulation exercise undertaken by 18 secondary school head teachers. A particular type of critical analysis is applied to the literature, and a phenomenographical approach is adopted for the scrutiny of the empirical data. Phenomenographic principles are utilised throughout the research, as they represent the only approach concerned directly with the different ways of understanding a phenomenon, and the relationships between understandings. From a range of literature, four abstracted understandings of what needs to be done to improve a school are discovered. They are based on reflecting on excellence, adapting leadership, interpreting the organisation, and developing the inter-dependence of active learning. Each understanding offers a framework through which specific aspects of the relevant literature can be interpreted, applied and integrated, within a given context. From the empirical research, five ways of understanding what needs to be done to improve a school are discovered. They consist of increasing knowledge diagnostically, encouraging a dynamic environment, involving stakeholders in the re-establishment of priorities, enforcing expectations, and co-ordinating initiatives through development planning. Our understanding of our work is an appropriate point from which to increase our competence, as it determines both what competences we develop, and how we develop them. Competence is increasingly concerned with how a situation is understood, what is required according to that understanding, and taking the necessary action. Competence is a consequence of the interaction between our understandings and the extent to which our work context empowers or controls us. For secondary school head teachers, it is argued that competence is dependent on how they understand what needs to be done to improve a school, and the extent to which their environments enable them to act on their understandings.
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Peet, Samuel. "Out-of-field dosimetry in contemporary radiation therapy." Thesis, Queensland University of Technology, 2022. https://eprints.qut.edu.au/234916/1/9325565_samuel_peet_thesis.pdf.
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Radiation therapy is a beneficial treatment for approximately half of all people diagnosed with cancer. This project improved the safety of radiation therapy for several vulnerable cohorts: pregnant patients, patients with electronic implants such as pacemakers, and young people at risk of developing secondary cancers later in life. In doing so, this research furthered equitable access to safe, high-quality health care.
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Wedel, Elsa. "Biology in Swedish Upper Secondary School : Does it Contribute to Ecocentrism?" Thesis, Linköpings universitet, Institutionen för fysik, kemi och biologi, 2019. http://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-157624.
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Environmental issues are increasingly on the agenda and education is recognised as an important part in turning the negative trend. Originally formulated in 1976, the intent of environmental education was toprotect the nature from human impact and to induce in students a sense of the natural worlds’ own values.However, this has come to change during the years and the focus now lies on the values that nature possess for humans, in the shape of education for sustainable development. Though creating a concern for the environmental issues, critics point out that the anthropocentric attitude is not as strongly committed to protecting the nature as the ecocentric attitudes are, and therefore suggest that ecocentrism should be included in the curriculums. Assuming that biology in Swedish upper secondary school is the only subject where such values may be considered this study examines whether there is a significant difference between students who undergo these classes and students who do not, in terms of their attitudes. The study was divided in two parts, where firstly a content analysis was performed to confirm that biology was indeed the only subject to include ecocentric values, and secondly a comparative study was performed with students (n=82) taking biology and students not taking biology in Swedish upper secondary school. The results imply that biology is unique in including ecocentric attitudes, however, not to the extent that was expected. Furthermore, the results reveal that there is no significant difference between students taking the biology classes and students who do not, implying that the subject biology is not successful in increasing students ecocentric attitudes.
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Dalmann, Romain. "Etude du mécanisme antalgique du Paracétamol ; région cérébrale et mécanisme mis en jeu." Thesis, Clermont-Ferrand 1, 2015. http://www.theses.fr/2015CLF1MM08/document.
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Le paracétamol est sujet à controverse depuis sa découverte. Que ce soit son mécanisme d’action, ses effets indésirables ou son efficacité, de nombreuses études ont été réalisées et parfois se contredisent. Parfois critiqué pour son efficacité limitée, il n’a pourtant rien à envier aux autres antalgiques : il soulage les douleurs faibles à modérées sans effets indésirables aux doses thérapeutiques. Cela en fait un médicament de premier recours chez la femme enceinte, le nourrisson et l’enfant. D’après un rapport de l’ANSM, sur les 30 substances actives les plus vendues en France en 2013 (montant total 1,15 milliard de boîtes), le paracétamol domine très largement (plus de 500 millions de boîtes). C'est l’antalgique et l’antipyrétique le plus consommé au monde. La pharmacopée des antalgiques est vieillissante, l’évolution de l’arsenal thérapeutique depuis 50 ans est limitée. Ce constat amène à réévaluer les stratégies de recherche. Maintenant, notre intérêt serait de comprendre les mécanismes et les cibles de ces antalgiques afin de développer des analogues plus affins tout en limitant leurs effets indésirables. Basée cette stratégie, le paracétamol est un parfait candidat. En effet, son mécanisme d’action n’est pas parfaitement connu mais son efficacité n’est plus à prouver. L’objectif de ces travaux est d’élucider le mystère qui entoure son mécanisme d’action et de découvrir ses cibles. Les dernières études redéfinissent le paracétamol comme un précurseur métabolique à l’origine d’un dérivé lipidique actif, nommé AM404. Ce dernier serait synthétisé dans certaines régions cérébrales exprimant l’enzyme FAAH capable de catalyser cette réaction. Le mécanisme alors mis en jeu montre que le paracétamol, via l’AM404, activerait les récepteurs TRPV1 centraux et indirectement les récepteurs CB1 pour renforcer un mécanisme central d’atténuation de la douleur via les voies descendantes sérotoninergiques. Cependant, le noyau cérébral concerné et le mécanisme cellulaire mis en jeu demeurent inconnus. Des données comportementales associées à une étude d’imagerie fonctionnelle ont levé le voile sur plusieurs régions cérébrales potentiellement impliquées dans l’action du paracétamol, notamment la substance grise périaqueducale. Cette dernière a suscité notre intérêt, car ce noyau exprime à la fois la triade FAAH/TRPV1/CB1, mais aussi est un carrefour des voies descendantes sérotoninergiques. Une activation dans la substance grise périaqueducale des récepteurs TRPV1 et CB1 est à même de produire un effet antinociceptif dépendant de ces contrôles descendants. Ces travaux de thèse ont conduit à conforter que l’action antalgique du paracétamol implique un mécanisme supra-spinal dépendant de l’enzyme FAAH en condition pathologique. Plus précisément, nous avons étudié le rôle de la triade FAAH/TRPV1/CB1 au niveau de la SGPA. Nous avons découvert que le paracétamol interagissait avec une voie de signalisation cellulaire mGLUR5-PLC-DAGL responsable de la production de l’endocannabinoïde 2-AG. Ce mécanisme pourrait à la fois expliquer l’étroite collaboration existant entre les récepteurs TRPV1 et CB1 dans l’effet antalgique du paracétamol et le renforcement des voies descendantes sérotoninergiques. Le paracétamol est donc un promédicament dont l’action cérébrale recruterait un ensemble de systèmes complexes pour médier son effet antalgique. Ce mécanisme séduisant ouvre la piste à de nouveaux antalgiques toujours plus efficaces avec des effets indésirables moindres, à l’image du paracétamolParacetamol is since its discovery controversial. Whether with respect to the mechanism of action, its side effects or effectiveness, many studies have been performed, at times contradictory. Sometimes criticized for its limited effectiveness, it has nothing to envy in contrast to other analgesics whose effectiveness are often associated with side effects. Paracetamol has proven itself to relieve low to moderate pain without side effects at therapeutic doses. This makes it drug of choice for pregnant women, infants and children. According to a report by the ANSM of the 30 top-selling active substances in France in 2013, with a total of 1.15 billion boxes, paracetamol largely dominates this ranking as its sales are over 500 million boxes. Thus it has become the analgesic and antipyretic most consumed in the world. Today, the pharmacopoeia of analgesics is outdated; evolution of the therapeutic arsenal for 50 years is limited with few major discoveries reported. This observation leads to the need to reassess research strategies to innovate new and more effective molecules. Until now, the aim was to focus on a few molecules with high therapeutic potential in order to optimize their effectiveness without understanding their mechanisms. Now our interest is to understand the mechanisms and targets of these analgesics in order to develop more comparable molecules while limiting their adverse effects. Based on this strategy, paracetamol is a perfect candidate. Indeed, its mechanism of action is not fully known, but its effectiveness is proven. The aim of this work is to elucidate the mystery surrounding its mechanism of action and discover its targets. The latest studies redefine paracetamol as a metabolic precursor to the origin of an active lipid derivative, called AM404. The latter is synthesized in certain regions of the brain expressing the FAAH enzyme capable of catalyzing this reaction. The mechanism thus put into play shows that paracetamol, via AM404, activates TRPV1 receptors and the central CB1 receptors indirectly to reinforce a central mechanism of pain relief via serotonergic descending pathways. However, the cerebral area concerned and the cellular mechanism involved remain unknown. Behavioral data associated with a functional imaging study unveiled several brain regions potentially involved in the action of paracetamol, including the periaqueductal gray matter. The latter sparked our interest for two reasons: one because it expresses the core triad FAAH/TRPV1/CB1; and two it also represents a crossroad of descending serotonergic pathways. Activation in the periaqueductal gray matter of the TRPV1 and CB1 receptors is adapted to produce an antinociceptive effect dependent on these descendant control systems. This work of this thesis has led to re-affirm that the analgesic action induced by paracetamol involves a supra-spinal mechanism dependent on the FAAH enzyme in pathological conditions. Specifically, we investigated the role of the triad FAAH/TRPV1/CB1 in the periaqueductal gray matter. We found that paracetamol interacted with the cell signaling pathway mGluR5-PLC-DAGL responsible for production of the endocannabinoid 2-AG. This mechanism can explain both the close collaboration between the TRPV1 and CB1 receptors in the analgesic effect of paracetamol and the reinforcing of serotonergic descending pathways. Paracetamol is thus a prodrug whose cerebral action involves a set of complex systems to mediate its analgesic effect. This attractive mechanism opens the track to new painkillers ever more effective with fewer side effects, reflected paracetamol mechanism
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Micallef-Roll, Joëlle. "Evaluation des effets psychocomportementaux de doses subanesthésiques de kétamine chez le sujet sain." Aix-Marseille 2, 2002. http://theses.univ-amu.fr.lama.univ-amu.fr/2002AIX20663.pdf.
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Malgré les avancées pharmacologiques avec les antipsychotiques «atypiques» certains patients schizophrènes ne sont pas améliorés par le traitement ou ne le tolèrent pas ou ne sont que partiellement améliorés avec la persistance des symptômes négatifs et des signes cognitifs. Aussi est-il nécessaire d'améliorer à la fois les outils diagnostiques et d'identifier des cibles pharmacologiques futures. Le système glutamatergique pourrait offrir cette double opportunité. L'implication du glutamate dans la physiopathologie de la schizophrénie repose, entre autres, sur le fait que la phencyclidine et la kétamine, antagonistes des récepteurs glutamatergiques NMDA soient à l'origine de. Symptômes rappelant étrangement les signes observés dans la schizophrénie. Aussi la compréhension des symptômes induits par la kétamine pourrait constituer une première approche dans cette nouvelle voie de recherche et le développement d'un « modèle » pharmacologiquement induit chez le sujet·sain permettrait d'orienter le choix des molécules lors des phases cliniques précoces. L'objectif de ce travail a été d'étudier cet outil pharmacologique en évaluant les effets de doses subanesthésiques de kétamine sur des indices perturbés chez le patient schizophrène et aisément explorés chez le sujet sain : les troubles de l'émotion, le traitement de l'information et les mouvements oculaires. Au cours de ces études réalisées au Centre de Pharmacologie Clinique et d’Evaluations Thérapeutiques, il a été montré que la kétamine à des doses subanesthésiques chez le sujet sain entraînait des effets psychomimétiques, d'apparition rapide, transitoires et réversibles, reproduisant ainsi les résultats d'études précédemment publiés. En outre, des anomalies de la sphère émotionnelle et du traitement de l'information ont été mises en évidence, grâce à des outils de mesure validés et sensibles (test des inductions des émotions et temps de réaction) et étaient comparables à celles observées chez le patient schizophrène. L'étude des effets de la kétamine sur l'oculomotricité dont l'analyse est en cours, nous permettra d'évaluer si cette molécule est aussi capable d'induire des anomalies oculaires documentées chez le schizophrène. L'ensemble de ces résultats permet d'envisager les aspects éthiques liés à·l’utilisation de la kétamine, la validité de cet outil pharmacologique et son utilité éventuelle pour l'exploration de nouvelles approches thérapeutiques.
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Burrows, Andrea C. "Secondary Teacher and University Partnerships: Does Being in a Partnership Create Teacher Partners?" University of Cincinnati / OhioLINK, 2011. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1307323122.
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Dupont, Stéphane. "Dose absorbée en surface en conditions d'obliquité dans les faisceaux de photons de haute énergie." Toulouse 3, 1994. http://www.theses.fr/1994TOU30204.
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Notre etude a consiste a obtenir un ensemble de donnees sur la variation de la dose absorbee a la surface et dans les premiers millimetres du milieu en fonction de l'angle d'incidence (de 0 a 80) pour differentes energies de faisceaux de photons (rx 4, 6, 10, 15 et 25 mv) et pour differentes ouvertures de collimateur de 5; a 300 cm#2. Afin de quantifier cette variation en fonction de l'obliquite, nous avons introduit un facteur d'obliquite. Pour chaque qualite de faisceau de photons, nous avons alors etudie l'evolution de ce facteur en fonction de la profondeur, de l'ouverture du collimateur et de l'incidence du faisceau. Les resultats de ces mesures indiquent que le facteur d'obliquite a l'entree du milieu est fortement dependant de ces differents parametres. Pour tester la validite de nos resultats experimentaux, nous avons egalement mene une etude theorique grace a un programme de calcul de dose associant la methode de monte-carlo et les techniques de calcul par convolution et par superposition. Ce programme, auquel nous avons apporte des modifications pour simuler les obliquites de surface, a ete d'une aide precieuse dans la comprehension et l'analyse du role respectif des electrons et des photons dans la mise en equilibre electronique lorsque l'angle d'incidence du faisceau varie. En definitive, le tres bon accord des variations theoriques et experimentales de la dose avec les differents parametres etudies a donc permis de proposer une interpretation physique pour chacune de ces variations. L'ensemble des resultats experimentaux et theoriques qui decoulent de ce travail a permis la mise en uvre d'une methode analytique de calcul de la dose absorbee a la surface de faisceaux de photons de haute energie pour differentes incidences et ouvertures de collimateur, en introduisant la notion de champ carre equivalent au champ d'entree deforme par l'incidence. Ces resultats ont permis egalement de proposer une methode de prise en compte des obliquites de surface dans le calcul des distributions de dose par ordinateur
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De, Graaf Brandon Michael. "Determining the Effect of Shielding for an Eye Exposed to Secondary Particles Produced by Galactic Cosmic Rays using MCNPX Modeling." University of Cincinnati / OhioLINK, 2010. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1288379556.
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Eiden, Céline. "Essai de faisabilité du suivi thérapeutique pharmacologique et de l'optimisation des antifongiques azolés récents : voriconazole et posaconazole." Montpellier 1, 2009. http://www.theses.fr/2009MON13508.
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Le voriconazole (VCZ) et le posaconazole (PCZ) sont des antifongiques récents à structure triazolée. Après avoir rapporté un cas d'allongement de l'espace QT avec torsade de pointes, suivi d'un arrêt cardiaque sous VCZ, nous avons effectué une étude sur l'ensemble des cas d'effets indésirables notifiés dans la Base Nationale de Pharmacovigilance et analysé les cas rapportés dans la littérature. Ces données nous ont permis de préciser les circonstances d'apparition des effets indésirables du VCZ. Nous avons ensuite mis au point et validé une méthode de dosage par chromatographie liquide haute performance avec détection ultraviolet du voriconazole et de son principal métabolite le N-oxide voriconazole. L'analyse du suivi thérapeutique et pharmacologique en conditions réelles de soins nous a ensuite permis d'établir un "profil de ratio métabolique de base" chez les patients immunodéprimés traités par VCZ dans le cadre d'une infection fongique invasive ou d'un traitement empirique. Enfin pour le PCZ, après avoir mis au point une méthode de dosage nous avons réalisé une étude pharmaco-clinique afin d'analyser les concentrations plasmatiques en PCZ à la posologie recommandée en traitement prophylactique ainsi que leurs variations dans une population de patients atteints d'hémopathies malignes. Notre travail s'intègre dans une démarche de qualité des soins visant à optimiser ces thérapeutiques chères, efficaces mais non dénuées d'effets indésirables.
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Stitzel, Cody Dee. "Empathetic Responding in Psychopathy Subtypes: Does Gender Equivalence between Offender and Victim Matter?" University of Dayton / OhioLINK, 2017. http://rave.ohiolink.edu/etdc/view?acc_num=dayton1502088898905774.
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Guerra, Cátia Carina de Almeida. "Salt effects on growth, nutrient and secondary compound contents of Diplotaxis tenuifolia." Master's thesis, Universidade de Aveiro, 2008. http://hdl.handle.net/10773/915.
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Mestrado em Biologia MarinhaA salinidade do solo é considerada, a nível mundial, como o principal factor abiótico de stress agrícola. Este facto levou ao desenvolvimento de diversos projectos em tolerância salina com o intuito de melhorar as culturas tradicionais e descobrir novas plantas passíveis de crescer nesses solos. Este trabalho centra-se nas respostas de crescimento de Diplotaxis tenuifolia Lquando cultivada sob condições de stress salino. O conhecimento do grau de tolerância salino desta planta é de grande interesse para a agricultura, uma vez que existem observações da ocorrência natural desta planta em zonas sujeitas a stress salino. As plantas foram cultivadas num gradiente de solução nutritiva com as concentrações de 0, 50, 100, 200 e 300 mM NaCl. Em todosos tratamentos as plantas não só sobreviveram, como cresceram e floriram. No entanto, notaram-se alguns sinais inibitórios de crescimento para os doisvalores de salinidade mais elevados. O peso seco e a área foliar foram medidos e a o crescimento relativo (RGR), bem como os seus componentes,rácio foliar unitário (Unit Leaf Ratio – ULR, comummente designado por NAR) e rácio de área foliar (Leaf Area Ratio – LAR), foram calculados. A expansão da área foliar decresceu com o aumento de salinidade. A produtividadefisiológica máxima (ULR) foi atingida nos 100 Mm NaCl. LAR foi provavelmente o maior responsável pelo ligeiro aumento nos valores de RGR, já que o ULR se manteve relativamente constante. No entanto o crescimento relativo manteve-se constante até 100 mM NaCl não apresentando diferençassignificativas. A acumulação de iões como Ca2+, Mg2+, K+, decresceu com o aumento da salinidade, ocorrendo comportamento inverso com o Na+, que atingiu valores bastante elevados nas salinidades mais altas. O rácio Na/K aumentou significativamente com o aumento da salinidade, sendo de notar que nas folhas velhas se obtiveram valores muito mais baixos que nas folhas novas, o que é indicativo da compartimentação do Na+ para as folhas mais velhas. O conteúdo total de polifenóis e do flavonóide queracitina foi máximo nos 50 mM NaCl. O conteúdo em azoto decresceu com o aumento da salinidade mas não tão acentuadamente como nos restantes iões (Ca2+, Mg2+, K+). Os resultados revelaram um crescimento óptimo desta planta asalinidades moderadas, com o máximo de produtividade (peso seco) a ser atingido a 100 mM NaCl. De acordo com o sistema de classificação usado, Diplotaxis tenuifolia foi classificada como uma espécie tolerante ao sal até um valor de salinidade máximo de 100 mM. Os resultados deste trabalho servirãode ajuda a programas de implementação de culturas de agricultura salina que visam uma maior sustentabilidade agrícola.
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Bannwarth, E. "Pancytopénie au méthotrexate à faible dose dans la polyarthrite rhumatoi͏̈de : à propos d'un cas et revue de la littérature." Bordeaux 2, 1992. http://www.theses.fr/1992BOR2M203.
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Martinetti, Florent. "Estimation des doses dues aux neutrons secondaires reçues par les patients en protonthérapie : cas des traitements ophtalmologiques." Paris 11, 2009. http://www.theses.fr/2009PA112250.
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Les travaux de recherche menés au cours de cette thèse ont eu pour objet d’évaluer les doses dues aux neutrons secondaires reçues par les organes du patient situés en dehors du champ de traitement. L’étude a été axée sur le cas des traitements ophtalmologiques réalisés à l’Institut Curie – centre de Protonthérapie d’Orsay (ICPO). En premier lieu, un modèle de la ligne de faisceau de 75 MeV utilisée pour ces traitements à Orsay a été développé avec le code de calcul Monte Carlo MCNPX. Dans un second temps plusieurs validations expérimentales du modèle ont été mises en œuvre. Elles concernent : (i) la distribution de dose des protons dans un fantôme d’eau, (ii) l’équivalent de dose ambiant dû aux neutrons secondaires, H*(10), ainsi que les spectres neutroniques dans la salle de traitement, et (iii) les doses déposées par les neutrons secondaires dans un mannequin anthropomorphe. L’accord entre les simulations et les mesures a été jugé suffisamment correct pour considérer le modèle de la ligne de traitement comme représentatif du faisceau utilisé en clinique à l’ICPO. L’estimation numérique des doses secondaires reçues par les organes du patient a été réalisée à l’aide d’un fantôme mathématique de type MIRD. Les doses absorbées dues aux neutrons secondaires ont été calculées pour plusieurs organes. Les valeurs les plus élevées, estimées au niveau de l’œil non traité, du cerveau et de la thyroïde, sont respectivement égales à 800, 310 et 235 µGy pour un traitement de 60 Gy équivalent 60Co délivrés à l’œil. Les organes recevant une dose équivalente supérieure à 1 mSv sont ceux situés sur la partie antérieure du corps, directement exposée aux neutrons générés dans la ligne de traitement. Un facteur 10 sur la dose équivalente est observé entre les organes situés à proximité de la zone traitée et ceux plus profond et éloignés du champ de traitement. L’utilisation du concept de dose efficace s’avère peu adapté pour caractériser la protection radiologique du patient en protonthérapieThe research work conducted during this thesis was to evaluate the neutrons secondary doses received by the organs of the patient outside the treatment field. The study focused on cases of eye treatments performed at the Institut Curie – Centre de Protonthérapie d’Orsay (ICPO). First, a model of the 75 MeV beam line used for the treatments at Orsay has been developed with the Monte Carlo code MCNPX. In a second time, several experimental validations of the model have been performed. They are: (i) the dose distribution of protons in a water phantom, (ii) the ambient dose equivalent due to secondary neutrons, H*(10) and the neutron spectra in the treatment room and (iii) the dose deposited by secondary neutrons in an anthropomorphic phantom. The agreement between simulations and measurements has been deemed sufficiently correct to consider the beam line model as representative of the beam used in clinics et the ICPO. The numerical estimation of secondary doses received by the organs of the patient was performed using a mathematical phantom type MIRD. The absorbed doses due to secondary neutrons were calculated for several organs. The highest values, estimated for the non treated eye, brain and thyroid, are respectively equal to 800, 310 and 235 μGy for a therapeutic dose of 60 GyE (60Co equivalent) delivered to the eye. The organs receiving an equivalent dose greater than 1 mSv are those located on the anterior part of the body directly exposed to neutrons generated in the beam line. A factor of 10 on the equivalent dose is observed between the organs located near the treated area and those located deeper and far from the treatment field. Using the concept of effective dose is not well adapted to characterize the radiological protection of patients in proton therapy
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Rosenthal, Robert. "How does student teacher research contribute to knowledge creation within the secondary school context?" Thesis, University of Sussex, 2014. http://sro.sussex.ac.uk/id/eprint/51479/.
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The extent to which participation in research is seen as an essential part of Initial Teacher Education programmes is very variable across time and institutions. Where it is a necessary part of the programme, student teachers are expected to engage in classroom enquiry and this is considered beneficial for them, the schools involved and to others more widely. This thesis explores student teacher research as knowledge creation, how the knowledge created by examples of the University of Sussex PGCE Special Study was used by the students, their school-based mentors and professional tutors and what effect this had on the culture of the schools. The research is presented through multiple embedded case studies derived from interviews with three participants in each of three schools: a student teacher researcher, their departmental mentor and the professional tutor. These are discussed through a micro-political lens by cross-section according to their collective role and holistically in relation to each school case. This analysis is further developed using a Bourdieusian analysis to support an understanding of how participants used the Special Studies to further their individual interests. The place of student research in the contested field of national initial teacher education policy is also discussed in order to highlight conflicted constructs of teacher professionalism. The ‘insider-outsider' binary is explored throughout the thesis and is reflected in its iterative methodology, types of knowledge, models of research, communities of practice and the researcher's own biography. Conflict and disruption are reviewed as offering creative potential and it is proposed that student teachers and their research are uniquely positioned to constitute a hybrid ‘semi-insider/outsider'. It is argued that by occupying this mid-space they can make a unique contribution to their school communities and the professional knowledge of teachers. However, the extent to which this takes place will depend on the potential that agents see for student research to further their own positional interests in a contested field. The thesis concludes that research projects can not only prepare student teachers for a research-active model of teacher professionalism, but also allow them to make an important contribution to partnership schools.
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Riemen, Anna Helene Katrin. "Does synovial hyperplasia after traumatic joint surface injury affect the development of secondary osteoarthritis?" Thesis, University of Aberdeen, 2018. http://digitool.abdn.ac.uk:80/webclient/DeliveryManager?pid=239453.
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The burden of osteoarthritis continuous to increase. While joint replacement surgery provides a cost effective and efficacious treatment for end stage osteoarthritis, no treatment exists to prevent or slow the progression of the disease. Understanding the cellular and molecular changes in the synovium following trauma and in early osteoarthritis could facilitate the identification of novel therapeutic targets. Previous studies identified synovial hyperplasia following intra-articular fractures, cartilage injury and in osteoarthritis. In mice, proliferation of synovial mesenchymal stromal/stem cells (MSCs) leads to synovial hyperplasia following joint surface injury. The driver for this expansion of MSCs in the synovium is unknown. Recently, YAP, a key downstream effector of the Hippo pathway, has been shown to causes tissue overgrowth due to modulation of MSC proliferation. The joint surface injury model of osteoarthritis was used to investigate whether YAP may play a role in synovial hyperplasia following joint surface injury. This work shows that synovial hyperplasia is common to both healer and non-healer mouse strains after joint injury and that Yap expression is up regulated on a protein and mRNA level. Using the same injury model in a mouse with a conditional knockout of Yap in Gdf5 lineage cells, showed that a Yap knockout in Gdf5 progeny cells prevented hyperplasia of synovial lining after joint surface injury, suggesting that YAP is required for MSCs in the synovium to proliferate. In patient synovial samples, YAP expression was up regulated in activated synovium, including a subset of CD55 positive fibroblast-like synoviocytes in the synovial lining. Proliferating cells were positive for active YAP. This suggests that findings in our mouse model are clinically relevant. Furthermore, modulation of YAP and synovial MSC proliferation after JSI provides a means to study the role of synovial hyperplasia after trauma. This could lead to a potential novel therapeutic target for the treatment of posttraumatic osteoarthritis.
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Andersson, Claes. "How does the moving of the family affect the outcome in swedish secondary school?" Thesis, Malmö högskola, Fakulteten för lärande och samhälle (LS), 2011. http://urn.kb.se/resolve?urn=urn:nbn:se:mau:diva-27944.
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Mitt syfte med detta arbete har varit att belysa det problem som det kan innebära för en skola atthantera elever som flyttat in under grundskoletiden och undersöka hur dessa elevers resultatpåverkas av det faktum att de har flyttat in från en annan skola.Den teori jag har använt är huvudsakligen systemteorin som den beskrivs i Peter Senges ”Denfemte disciplinen”. Jag valde denna teori eftersom frågeställningen i detta arbete förutsätter attman intar ett övergripande perspektiv på frågor som rör hela den svenska grundskolan – helasystemet.I undersökningen används till största delen statistiska metoder för att ta fram och analysera hurstor andel av eleverna i tre svenska grundskolor i en kommun som har flyttat under singrundskoletid och hur det har påverkat deras resultat, mätt som meritvärde i slutet av årskurs nio.Undersökningen visar att deras resultat, mätt som genomsnittet av meritvärdena i årskurs nio ärsignifikant lägre än genomsnittet för den aktuella årskullen. Mer studier kommer att behövas föratt säkerställa reliabiliteten i undersökningsresultatet och framför allt för att kunna diskuteralämpliga åtgärder för att hantera dessa resultat.How the moving of the family affect student outcome in Swedish secondary school. I found that students in a community that have moved at least once during their nine years in the Swedish compulsory school get significantly lower grades than others.
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Gerrard, Edward. "How does coursework based study affect the learning of pupils in secondary science education?" Thesis, University of Gloucestershire, 2010. http://eprints.glos.ac.uk/3254/.
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The GCSE science syllabus and curriculum changed considerably between 2005 and 2008. A key specification of coursework which had been identified as encouraging routine completion was replaced, requiring coursework to be completed under exam conditions, while a vocational alternative with increased coursework content was also introduced. I set out in this PhD study, as a 'researching teacher', to ascertain the attitudes of pupils and teachers to GCSE science coursework, and whether there exist any differences in pupil attainment linked to the reform of coursework and GCSE examination. I also have looked at how pupils learn in science through completing coursework as part of an evaluation of the effectiveness of coursework in the GCSE science curriculum. This thesis takes the form of a case study comprising reflecting a practitioner based enquiry using mixed methods methodology. It is therefore an integrated longitudinal design combining qualitative and quantitative methods. Qualitative data was elicited from interviews, questionnaires, observation and field notes. Quantitative analyses were undertaken of pupil performance in coursework and examination results. Key research findings include confirmation that many pupils in the case study preferred a coursework based approach to their science education, and they found they learned more from this approach. Pupils were also found to prefer learning when a constructivist model of teaching and learning was adopted in the classroom. Active learning led to improvements in understanding and completing coursework. Additional analysis of quantitative data showed that many pupils achieved Significantly better grades for their science coursework than they did through examinations. Further, the data revealed when coursework can be improved using an assessment-based approach to learning, and that there Were no Significant statistical differences between boys and girls in coursework and examination results. The research revealed that when coursework for GCSE science is reviewed and improved as part of a constructivist model of learning, there is a positive contribution to attainment levels in the GCSE examination. Furthermore, there is a need to consider how the format of that coursework ensure it does not encourage routine completion, but instead encourages assessment for learning, active learning and individual responsibility for learning. The thesis, overall, represents a personal, scholarly and professional engagement in understanding the work of teaching GCSE science.
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Leech, Andrea Dawn. ""What Does This Graph Mean?" Formative Assessment With Science Inquiry to Improve Data Analysis." PDXScholar, 2014. https://pdxscholar.library.pdx.edu/open_access_etds/1537.
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This study investigated the use of formative assessment to improve three specific data analysis skills within the context of a high school chemistry class: graph interpretation, pattern recognition, and making conclusions based on data. Students need to be able to collect data, analyze that data, and produce accurate scientific explanations (NRC, 2011) if they want to be ready for college and careers after high school. This mixed methods study, performed in a high school chemistry classroom, investigated the impact of the formative assessment process on data analysis skills that require higher order thinking. We hypothesized that the use of evaluative feedback within the formative assessment process would improve specific data analysis skills. The evaluative feedback was given to the one group and withheld from the other for the first part of the study. The treatment group had statistically better data analysis skills after evaluative feedback over the control. While these results are promising, they must be considered preliminary due to a number of limitations involved in this study.
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陳素心 and So-sum Chan. "How does principal's leadership influence teachers' beliefs?: case study of a secondary school in HongKong." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2002. http://hub.hku.hk/bib/B31962798.
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Dewar, Louise H. "The advanced placement program| Does the cost outweigh the value for independent schools in the 21st century?" Thesis, College of Saint Elizabeth, 2014. http://pqdtopen.proquest.com/#viewpdf?dispub=3619006.
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The purpose of this action research, mixed methods study was to explore the impact of the AP Program on the high school and college experience of students, both from an academic and a "lived experience" perspective. In addition, the study investigated the costs and values of the AP Program to the institution itself. The study revealed that the AP Program continues to contribute significant value to students' high school educations, generally prepares them well for success at college, and often contributes to the acquisition of important credit and placement accommodations for students when matriculating at college. The study also revealed that, although the Program contributes a great deal of stress to the high school experience, students do not see this as a significant impediment to participation. However, the study also revealed several opportunities for the institution to better prepare students for the rigor of the Program and their use of AP scores in obtaining accommodations at college. Finally, the study demonstrated that while the AP Program contributes important value to the teaching experience, marketing of the institution, and the college admissions success of the school, there are important issues that warrant further consideration and review, not the least of which is the quality of the non-AP curriculum that is offered to students who do not meet the prerequisites of the AP Program.
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Reeves, Todd. "Does Content Knowledge Matter for New Teachers?" Thesis, Boston College, 2013. http://hdl.handle.net/2345/3346.
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Thesis advisor: Joseph J. PedullaThere is considerable evidence that new teachers are ill prepared for classroom practice, including self-reported evidence collected from teachers (e.g., Levine, 2006), and statistical evidence for differences in the achievement of students with new versus more experienced teachers (Rivkin, Hanushek, and Kain, 2005). In light of the challenges encountered by new teachers (e.g., Levine, 2006), this study examined the value of different forms of teacher knowledge for teachers with different levels of experience. In particular, this study investigated the interactive relationship between teaching experience and teacher content knowledge, and student achievement in mathematics and science. In New York City, Boyd et al. (2009) linked practice-focused teacher preparation to student mathematics achievement in the first year of teaching and teacher content preparation to achievement in the second. However, other studies demonstrated interactions between teaching experience and content knowledge with different interpretations (e.g., Kukla-Acevedo, 2009; Monk, 1994). At the same time, this study examined the interactive relationship between teaching experience and teachers' pedagogical content knowledge, and student achievement. Extant models of teacher career development (Huberman, 1989; National Research Council, 2010) and how teacher education affects student achievement (e.g., Desimone, 2009) offered theoretical grounding for the study. With nationally representative samples of fourth and eighth grade U.S. students--participants in the 2011 Trends in International Mathematics and Science Study--this study employed hierarchical linear modeling to address its research questions among an array of student achievement outcomes in the domains of mathematics and science. This study attempted to account for salient student, teacher, and contextual factors, and the probabilities of teachers' receipt of various teacher education "treatments" (i.e., propensity score analysis) to reduce the plausibility of selection threats to internal validity. The study found no evidence for relationships between teacher content knowledge or pedagogical content knowledge and student mathematics and science achievement in fourth and eighth grade. Furthermore, the results indicated no interactive relationships between forms of teacher knowledge and teaching experience, and student achievement in these grades/subjects. The limitations of cross-sectional, observational studies using large-scale data and directions for further research are discussed
Thesis (PhD) — Boston College, 2013
Submitted to: Boston College. Lynch School of Education
Discipline: Educational Research, Measurement, and Evaluation
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Gonon, Géraldine. "Space radiation-induced bystander effect : kinetics of biologic responses, mechanisms, and significance of secondary radiations." Phd thesis, Université de Franche-Comté, 2011. http://tel.archives-ouvertes.fr/tel-00987717.
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Widespread evidence indicates that exposure of cell cultures to α particles results in significant biological changes in both the irradiated and non-irradiated bystander cells in the population. The induction of non-targeted biological responses in cell cultures exposed to low fluences of high charge (Z) and high energy (E) particles is relevant to estimates of the health risks of space radiation and to radiotherapy. Here, we investigated the mechanisms underlying the induction of stressful effects in confluent normal human fibroblast cultures exposed to low fluences of 1000 MeV/u iron ions (linear energy transfer (LET) ~151 keV/µm), 600 MeV/u silicon ions (LET ~50 keV/µm) or 290 MeV/u carbon ions (LET ~13 keV/µm). We compared the results with those obtained in cell cultures exposed, in parallel, to low fluences of 0.92 MeV/u α particles (LET ~109 keV/µm).Induction of DNA damage, changes in gene expression, protein carbonylation and lipid peroxidation during 24 h after exposure of confluent cultures to mean doses as low as 0.2 cGy of iron or silicon ions strongly supported the propagation of stressful effects from irradiated to bystander cells. At a mean dose of 0.2 cGy, only ~1 and 3 % of the cells would be targeted through the nucleus by an iron or silicon ion, respectively. Within 24 h post-irradiation, immunoblot analyses revealed significant increases in the levels of phospho-TP53 (serine 15), p21Waf1 (also known as CDKN1A), HDM2, phospho-ERK1/2, protein carbonylation and lipid peroxidation. The magnitude of the responses suggested participation of non-targeted cells in the response. Furthermore, when the irradiated cell populations were subcultured in fresh medium shortly after irradiation, greater than expected increases in the levels of these markers were also observed during 24 h. Together, the results imply a rapidly propagated and persistent bystander effect. In situ analyses in confluent cultures showed 53BP1 foci formation, a marker of DNA damage, in more cells than expected based on the fraction of cells traversed through the nucleus by an iron or silicon ion. The effect was expressed as early as 15 min after exposure, peaked at 1 h and decreased by 24 h. A similar tendency occurred after exposure to a mean absorbed dose of 0.2 cGy of 3.7 MeV α particles, but not after 0.2 cGy of 290 MeV/u carbon ions.Analyses in dishes that incorporate a CR-39 solid state nuclear track detector bottom identified the cells irradiated with iron or silicon ions and further supported the participation of bystander cells in the stress response. Mechanistic studies indicated that gap junction intercellular communication, DNA repair, and oxidative metabolism participate in the propagation of the induced effects.We also considered the possible contribution of secondary particles produced along the primary particle tracks to the biological responses. Simulations with the FLUKA multi-particle transport code revealed that fragmentation products, other than electrons, in cells cultures exposed to HZE particles comprise <1 % of the absorbed dose. Further, the radial spread of dose due to secondary heavy ion fragments is confined to approximately 10-20 µm Thus, the latter are unlikely to significantly contribute to the stressful effects in cells not targeted by primary HZE particles.
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Watts, Kim. "Does teenage pregnancy and childbirth really increase risk? : exploring outcomes through secondary analysis of NHS data." Thesis, University of Nottingham, 2010. http://eprints.nottingham.ac.uk/12590/.
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This retrospective cohort study, examined pregnancy and birth related outcomes for 32,895 births between 1st January 1992 and 31st December 2001 in two maternity units in the East Midlands. The study compared seven outcomes in younger teenagers (<16 year), older teenagers (17-19 years) and a comparison group (20-25 year olds). The sample included 1105 births to younger teenagers, 6923 to older teenagers and 24867 to the comparative group. 14824 were to primiparous women and 18071 were to multiparous women of which 1711 births to multiparous women were rapid repeat births (<18 months of a previous birth). Results showed that compared to those in their early 20s, primiparous teenagers had an increased risk of antepartum haemorrhage (APH) (<16, OR=1.67,95% CI 1.262 to 2.227; 17-19, OR=1.48,95% CI 1.253 to 1.751) and low Apgar score (<16, OR=1.36,95% CI 1.102 to 1.669; 17-19, OR=1.15, 95% CI 1.023 to 1.297) but were less likely to have an instrumental birth (<16, 0R=0.64,95% CI 0.499 to 0.819; 17-19, OR=0.708,95% CI 0.622 to 0.807) or perineal trauma (<16, OR=0.63,95% CI 0.534 to 0.745; 17-19, OR=0.667, 95% CI 0.608 to 0.734). Teenagers had a similar statistical risk as the comparative group for lower segment Caesarean section (LSCS), low birth weight (LBW) and premature birth. Compared to those in their early 20s multiparous older teenagers had a reduced risk of both instrumental (OR= 0.711, 95% CI 0.555 to 0.912) and perineal trauma (OR=0.863, 95% CI 0.752 to 0.99 1) but in younger teenagers there was a similar risk. Multiparous teenagers were at an increased risk of premature birth (<16, OR=1.934,95% CI 1.153 to 3.243; 17-19, OR=1.227,95% CI 1.043 to 1.442) but for LSCS, low Apgar score and low birth weight a similar statistical risk was found as the comparative group. When comparing multiparous teenagers with primiparous teenagers, multiparous teenagers had a reduced risk of instrumental birth (OR=0.429, 95% CI 0.339 to 0.541), perineal trauma (OR=0.668, 95% CI 0.595 to 0.750), low Apgar score (OR=0.782,95% CI 0.664 to 0.921) and LBW (OR=0.760, 95% CI 0.587 to 0.982) but an increased risk of premature birth (OR=1.269, 95% CI 1.061 to 1.517). For the remaining outcomes both primiparous and multiparous teenagers had a similar statistical risk. Teenagers having a rapid repeat birth had a reduced risk of instrumental birth (OR=0.32, 0.110 to 0.931) but an increased risk for premature birth (OR=1.617 95% CI 1.150 to 2.272). For APH, Apgar score and LBW teenagers having a rapid repeat birth had a similar statistical risk to those who had not. In conclusions teenagers should not be treated as a homogenous group and outcomes should be investigated separately for age groupings and parity as teenagers birth well and only APII and neonatal complications are worse in some groups of teenagers.
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Tong, Chung-fan, and 湯仲勳. "How does the teamwork culture affect the teachers' ways of working in a local secondary school?" Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2004. http://hub.hku.hk/bib/B30257141.
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Davids, Eugene Lee. "Does family structure matter? A comparison of the goals and aspirations of learners in secondary school." University of the Western Cape, 2012. http://hdl.handle.net/11394/5115.
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Magister Artium - MASelf Determination Theory (SDT) proposes that individuals are motivated to have goals and aspirations which are either intrinsic or extrinsic in nature. Intrinsic life goals are associated with greater psychological health and well-being. Research shows that family structure plays a role in the way children are raised and has implications for later adult adjustment. In South Africa 42.8% of children are raised in a single parent household. This study aimed to compare the goals and aspirations of learners from single and married parent households. The study used a quantitative methodology with a cross-sectional comparative research design. The sample consisted of 853 Grade 11 learners from schools in the Northern, Southern and Metro Central Education Districts in the Western Cape. The data was collected using a selfreport questionnaire that consisted of two sections, demographical information and the Aspirations Index. The Aspirations Index assessed the life goals of the learners and categorised the goals and aspirations into intrinsic and extrinsic life goals. The data was analysed using the Statistical Package for Social Sciences V20 (SPSS). The results suggest that there was a significant main effect of family structure on certain goals and aspirations of Grade 11 learners in secondary schools. These goals and aspirations included wealth, image, personal growth, relationships and health. Furthermore, participants from single parent households placed more emphasis on intrinsic goals than participants from married parent.
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Chan, So-sum. "How does principal's leadership influence teachers' beliefs? : case study of a secondary school in Hong Kong /." Hong Kong : University of Hong Kong, 2002. http://sunzi.lib.hku.hk/hkuto/record.jsp?B25752091.
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Wood, J. M. "To what extent does school leadership facilitate Community Cohesion for students in an English secondary school?" Thesis, University College London (University of London), 2017. http://discovery.ucl.ac.uk/1536125/.
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This thesis is a study of the implementation of the policy of Community Cohesion in one maintained secondary school in England. It explores the policy cycle through the stages of influence, production and practice and notes how discourses at national and local levels influenced the policy. The literature review considers the discourses of multiculturalism, interculturalism, citizenship, identity and security that influenced the policy at its inception at national level. The case study examines documentary evidence including the racist incidents log and elicits the views of staff and students through interviews and focus groups addressing the process of implementation. The study uses the standards set by the ministry to describe and evaluate Community Cohesion in the study school. The analysis seeks to explain the outcomes of the Community Cohesion policy and the relative influence of national and school level discourses on the practice of Community Cohesion. The top down dominant discourse identified as influencing the policy is neo-liberalism, expressed in the national drive for standards and effectiveness and prioritising results. The system leadership model, adopted by the school’s leaders, accommodates to 4 the national agenda but also includes a moral purpose that influences the local response both to standards and to Community Cohesion. During the study, inspectors recognised the school as effectively developing Community Cohesion. The research identifies the extent to which the successful outcomes can be attributed to the influence of the system leadership that enables individual school leaders to exercise initiative based on moral purpose, personal conviction and positive relationships. Examples include a focus on the achievement of all students, a link to the local Jewish school and a twinning link with Kenya. The sense of moral purpose was disseminated through the leadership team’s interactions with the school community, school activities and the school’s newsletter.
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Svensson, Ofir. "Does small-scale land use affect the understory birds negative in the Peruvian National Reserve Allpahuayo Mishana?" Thesis, Högskolan i Halmstad, Sektionen för ekonomi och teknik (SET), 2014. http://urn.kb.se/resolve?urn=urn:nbn:se:hh:diva-25017.
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Human activities that lead to fragmentation and habitat loss are big problems in the world. Due to global climate change the negative effects of fragmented habitats can be catastrophic for many organisms. In the Amazon rainforest, that is most sensitive to human impact, stands a big risk to lose its species diversity. Fragmentation and climate change together seems to escalate the death rate of rainforest plants and that will change the whole ecosystem. Birds and insects are depending on the trees and the trees faces big challenges now. Many of the rainforest organisms have been noticed to emigrate further up to northern altitudes due to the warmer climate and maybe also because of deforestation. Many of the lowland forest birds are predicted to distribute from their origin habitats. The national reserve Allpahuayo Mishana in the Peruvian Amazon is known for its diversity of birds. It is a big challenge for the reserve to maintain the origin forest composition from climate change, which will lead to losses of species. The reserve allows the local community to utilize the land for small-scale uses inside the protected zone. Many of the birds are sensitive for external disturbance. Most human activities are resulting in that the forest becomes less dense, which can lead to that the territory for the birds decreases. This makes it important for the reserve to improve the human land use not to restrict the birds' habitat inside the reserve. This project will investigate if the small-scale land uses affects the understory birds’ diversity and habitat negative. The purpose is to see if the fragmented forests in the reserve, closest to the utilized land, can functioning as a secondary forest for the understory birds, or are the understory birds limited by the small-scale land use, in the national reserve Allpahuayo Mishana? Four sites with various human activities were chosen to investigate if the sites contain any understory birds. The result showed that the most disturbed sites had poor bird diversity compare to the sites with no human disturbance.
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Vardinakis, Mindie H. C. "Does Student Choice Improve Students' Attitudes Toward their Language Arts Class?" Defiance College / OhioLINK, 2008. http://rave.ohiolink.edu/etdc/view?acc_num=def1281705744.
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Hostutler, Roger Allen. "Comparison of Effects of Daily and Pulse Dose Calcitriol in Treating Renal Secondary Hyperparathyroidism in Cats with Primary Chronic Renal Failure." The Ohio State University, 2004. http://rave.ohiolink.edu/etdc/view?acc_num=osu1396282849.
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Cardoso, Jorge Luiz. "Evaluation of the precipitation of secondary phases on CO2 environment corrosion resistance of austenitic and super austenitic stainless steels." reponame:Repositório Institucional da UFC, 2016. http://www.repositorio.ufc.br/handle/riufc/18440.
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CARDOSO, J. L. Evaluation of the precipitation of secondary phases on CO2 environment corrosion resistance of austenitic and super austenitic stainless steels. 2016. 133 f. Tese (Doutorado em Ciência de Materiais) – Centro de Tecnologia, Universidade Federal do Ceará, Fortaleza, 2016.Submitted by Hohana Sanders (hohanasanders@hotmail.com) on 2016-07-15T13:48:21Z No. of bitstreams: 1 2016_tese_jlcardoso.pdf: 8753874 bytes, checksum: a423033a537ecd65f676406b27740c08 (MD5)
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Austenitic stainless steels are widely used in several applications including the manufacture of pipelines for the oil and gas industry. This work discusses the corrosion behavior of austenitic and super austenitic stainless steels in CO2-containing environments. The steels used in this work were the AL-6XN PLUS™ (UNS Designation N08367) and 904L (UNS Designation N08904) super austenitic stainless steels. Two conventional austenitic stainless steels, 316L (UNS S31600/ S31603) and 317L (UNS S31703) were also used for comparison purposes. Potentiodynamic polarization measurements were taken in CO2-saturated synthetic oil field formation water, deaerated with nitrogen to simulate some conditions in the pre-salt region. Potentiostatic measurements were also carried out to evaluate the corrosive level of the solution without the presence of CO2. Pressurized experiments using autoclave in CO2-containing environment and in synthetic air environment were also conducted to evaluate the corrosion resistance of the alloys when pressure and temperature act together. Heat treatments at high temperatures between 600 °C and 760°C in different ranges of time were also conducted to evaluate the possible sigma phase precipitation and its effect on the corrosion resistance. The AL-6XN PLUS™ and 904L super austenitic stainless steels showed a good performance in CO2-containing environment. The AL-6XN PLUS™ steel also exhibited the best performance in the pressurized experiments. The conventional 316L and 317L steels showed susceptibility to pitting and crevice corrosion. The results showed that the conventional alloys are not suitable for the use in CO2-containing environment under severe conditions. Pitting potential of the 316L alloy was affected by the pH of the solution in CO2-saturated solution. No sigma phase precipitated in the heat treatments for the range of time used indicating that its precipitation kinetics in austenitic stainless steels is very slow. This result is an advantage when working with austenitic stainless steels for long periods of exposure at high temperatures.
Os aços inoxidáveis austeníticos e super austenític os são amplamente utilizados na fabricação de tubulações na industria de petróleo e gás. Esse trabalho discute o comportamento da corrosão de aços inoxidáveis austeníticos e super a usteníticos em meio contendo CO 2 . Os aços usados nesse trabalho foram os aços super aust eníticos AL-6XN PLUS™ (Designação UNS N08367) e 904L (Designação UNS N08904). Dois aç os austeníticos convencionais, 316L (UNS S31600/ S31603) e 317L (UNS S31703), tamb ém foram usados para comparação. Foram realizadas medidas de polarização potenciodinâmica em água artificial de formação de poço de petróleo saturada com CO 2 e desaerada com nitrogênio para simular algumas condições do pré-sal. Foram também realizad as medidas potenciostáticas para avaliar o nível corrosivo da solução sem a presença de CO 2 . Experimentos pressurizados usando autoclaves em meio contendo CO 2 e ar sintético também foram realizados para avalia r a resistência à corrosão das ligas quando pressão e t emperatura agem juntas. Foram realizados tratamentos térmicos em altas temperaturas entre 60 0 °C e 760 °C em diferentes faixas de tempo para avaliar a formação de fase sigma e seu e feito na resistência à corrosão. Os aços super austeníticos AL-6XN PLUS™ e 904L mostraram um a boa performance em meio contendo CO 2 . O aço AL-6XN PLUS™ também exibiu uma boa performa nce nos experimentos pressurizados. Os aços convencionais 3 16L e 317L apresentaram susceptibilidade à corrosão por pites e frestas. Os resultados mostraram que os aços convencionais não são apropriados para uso em meio contendo CO 2 sob condições severas. O potencial de pite do aço 316L foi afetado pelo pH d a solução em meio saturado com CO 2 . Não houve precipitação de fase sigma nos tratamento s térmicos para as faixas de tempo usadas indicando que sua cinética de precipitação e m aços inoxidáveis austeníticos é muito lenta. Esse resultado é uma vantagem ao se trabalha r com aço inoxidáveis austeníticos em logos períodos de exposição em altas temperaturas.
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Minjares, Amador Jr. "Human skeletal remains of the ancient Maya in the caves of Dos Pilas, Guatemala." Thesis, Texas A&M University, 2003. http://hdl.handle.net/1969.1/243.
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This study focuses on the assessment of the depositional activity that occurred in six caves of the Petexbatun region of the Peten, Guatemala through a quantitative analysis of the human skeletal material recovered from them. Five of these caves are associated with the site of Dos Pilas; the sixth cave (Cueva de Los Quetzales) is located beneath the site of Las Pacayas. The cave is an important aspect of the Maya worldview, as evidenced in the artifactual and skeletal material found in caves by archaeological exploration. My study is specifically focused on the assessment of the primary and/or secondary burial of Maya dead within these caves via analyses of the relative skeletal element frequencies, the minimum and probable number of individuals, and the identification of human cut marks. Based on these lines of evidence and data from preliminary reports, between 100 and 150 individuals of both sexes and various age groups were primarily deposited/buried in these caves. Secondary activity may be inferred based on evidence of human-made cut marks on several elements. There is no osteological evidence to support the hypothesis of human sacrifice. I was unable to determine the status of the individuals deposited in the caves. The best interpretation is that several types of depositional activity occurred within these caves over time.
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Petersson, Theres. "Peer Feedback in a Swedish EFL Textbook -Does it align with best practices?" Thesis, Örebro universitet, Institutionen för humaniora, utbildnings- och samhällsvetenskap, 2021. http://urn.kb.se/resolve?urn=urn:nbn:se:oru:diva-92956.
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Peer feedback and its role for students’ language learning receive considerable interest in thefield of English as a foreign language. A related area of interest is the ways in which teachersare trained in their use of peer feedback and its integration into their classroom practice. Yet,research on the ways in which English language textbooks include opportunities for andinstructions in peer feedback are sparse. Given the importance of textbooks in EFLclassrooms as one of the primary sources of L2 input, the aims of this study are to investigate:1) Whether commonly used textbooks for teaching English in Swedish upper-secondaryschools recommend or integrate peer feedback, and what a) the frequency, and b) type ofthese recommendations and exercises are. 2) How the recommendations and exercises alignwith a) recommendations and best practices as identified in the literature, and b) the nationalcurriculum and the syllabus for English 7.To answer these questions, we analyze one of the most commonly used textbooks for teachingEnglish 7 in Swedish upper-secondary schools, Blueprint C Version 2.0. The findings showonly two instances in the book where the use of peer feedback is promoted as a valuablestrategy for improving the quality of students’ productions. It also shows that the bookcontains a total of 52 writing and speaking exercises, out of which 30 include the use of peerfeedback that, to some extent, aligns with best practice recommendations. As for thealignment with the curriculum and syllabus, the identified recommendations and support forthe use of peer feedback, as well as the peer feedback exercises, are shown to specificallymeet one of the goals of the national curriculum and three of the bullet points listed in thecore content in the syllabus for English 7.
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Chiu, Suk-kwan, and 趙淑君. "Does the relative age effect (RAE) exist in the selection of athletes in Hong Kong secondary schools?" Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2005. http://hub.hku.hk/bib/B45013834.
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Bhogal, Balbir Kaur. "How does patient choice impact on secondary care : an in depth investigation in a large teaching hospital." Thesis, University of Birmingham, 2016. http://etheses.bham.ac.uk//id/eprint/6490/.
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Over recent decades health care policy in the English NHS has focused on the role of patient choice of provider as a lever for health care improvement (Mays 2010; Fotaki 2013). The thesis explores the degree to which patient choice policy has been successful in its aim. Specifically, it explores the influence that patient choice policy has on changing and shaping organisation culture in an acute hospital trust. A qualitative case study was undertaken in a teaching hospital Trust involving interviews with 30 interviewees drawn from different levels of the hierarchy in the hospital. The study also reviewed documents to understand where PCP was positioned in the hospitals ambition. The study found that patient choice had not changed organisational behaviour in the hospital and did not have the desired impact as expected by policy makers. The study identified that the PCP programme theory had failed to recognise the impact that the culture of an organisation has on change. The culture of the hospital was still one of ‘knowing what was best for its patients’ and rejecting the notion that patients wanted choice. Also, the incentives of patient choice policy were considered weak in the context of hospitals overrun with demand and competing priorities.
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Brooks, Kanini Wanjira Ward. "Does an Online Post-baccalaureate Secondary Teacher Certification Program Produce Certified Teachers Who Remain in the Field?" Thesis, University of North Texas, 2015. https://digital.library.unt.edu/ark:/67531/metadc804832/.
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Given issues in education concerning teacher shortages, the omnipresence of alternative certification programs and the growth of online programs in higher education, this study investigated teacher retention for 77 secondary education teachers who completed an online teacher preparation program in Texas. Teacher retention was examined from 2003-2013 and investigated the influence of factors such personal characteristics, working conditions and school setting characteristics on teacher retention. Data was collected electronically utilizing a survey instrument designed by two teacher education experts and I. A total of 21 variables and two open-ended questions were investigated using the survey instrument. Exploratory factor and hierarchical multiple regression analyses were conducted to identify a multi-factor model for teacher retention utilizing the participants' survey responses. These analyses yielded evidence of the program's effectiveness in preparing teachers for long careers. Specifically, the areas of program support, field experience, and classroom management were statistically significant factors that contributed positively to teacher retention. Additionally, variables outside the program, were examined. These factors included personal characteristics, working conditions, and school setting factors. The predictor model accounted for 56% of the variance; F (17, 54) = 3.015; p = < 0.001. In particular, working conditions contributed to 41% of the variance associated with the teacher retention model. A qualitative analysis of open-ended survey questions was used to further examine decisions to remain in teaching. Support of administration, colleagues, staff, and parents was shown to influence teacher retention.
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Faaulufalega, Tailetai Pale. "How does Culture Impact on Educational Leadership in Samoa?" The University of Waikato, 2008. http://hdl.handle.net/10289/2260.
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The aim of this research was to explore the relationship between culture and the educational leadership of six secondary school principals in Samoa. Educational leadership is a bounded process and is subject to the cultural traditions and values of the society in which it is exercised. To date, no research has been undertaken on this topic in Samoa. This qualitative study used a semi-structured interview process to gather data from the secondary school principals who had been principals for more than three years in government schools. It also sought to explore how professional development of the principals might be undertaken. The principals in this study were interviewed both face-to-face and by telephone. The findings revealed that culture significantly impacted on their leadership. The matai culture was particularly influential. For example, respect, Christianity, role modelling and the importance of using the Samoan language to communicate within the school context were all influential. The findings also revealed the effective leadership styles applicable to Samoan school context in relation to indigenous cultural leadership. For example, inclusive/consensus/collaborative leadership style that is practiced in Samoan culture is effectively used by principals to lead schools. The organisational culture of the Ministry of Education Sports and Culture in Samoa (MESC) also considerably impacts on educational leadership. For example, the policies from the MESC sometimes contradict with the practice of the principals, such as the principal's practice of corporal punishment is a crime in the MESC and United Nation policies. This research also revealed the gap between the western models of leadership and the Samoan indigenous cultural context and leadership practice by the principals. Therefore, all the principals involved in this study positively engaged with their Samoan cultural values and beliefs to lead schools effectively. However some Samoan indigenous cultural values and beliefs impact negatively on the education system. They need to be considered so as not to inhibit the development of educational leadership of Samoan principals. Today's education has grown rapidly in terms of technology therefore educational leaders must adapt and change their leadership. Principals must be professionally trained so that they would lead effectively. According to Smith (1992, p. 9) To change education is to change society
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Nascimento, HÃlio Oliveira do. "Study of the chemical and cytotoxic potential of secondary metabolites of endophytic fungus Periconia hispidula." Universidade Federal do CearÃ, 2016. http://www.teses.ufc.br/tde_busca/arquivo.php?codArquivo=16271.
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CoordenaÃÃo de AperfeÃoamento de Pessoal de NÃvel SuperiorConselho Nacional de Desenvolvimento CientÃfico e TecnolÃgico
Periconia hispidula is an endophytic fungus isolated from dried leaves from semi-arid dunes of Bahia. The fungus was subjected to cultivation by varying nutritional factors in four different culture mediuns: MPD (malt, peptone and dextrose), BD (potato dextrose), BDL (potato, dextrose and yeast) and MntPL (mannitol, peptone and yeast), and analyzing the extracts on different incubation days (7, 14, 21, 28 days). A survey of primary cytotoxic activity was carried out from the extracts against tumor cell line of colon cancer (HCT-116). The MPD extracts - 28 days BDL - 28 days and BD - 21 days showed a promising cytotoxic activity and were preliminarily selected for the chemical study. The chromatographic fractionation of MPD-28 days extract resulted in the isolation of 11 secondary metabolites characterized as {4-chromanone, 6-hydroxy-(R) -methyl- (PS-1)}, {4-chromanone, 6-hydroxy-(S) -methyl- (PS-2)}, {E, 1-(2,5 dihydroxyphenyl) but-2-en-1-one (PS-3)}, {1-(2, 5 dihydroxyphenyl)-butan-1-one (PS-4)}, {Z-methyl-3-(3-hydroxyphenyl) propenoate (PS-5)}, modiolide A (PS-7), fusanolide B (PS-8), stagonolide E (PS-9), {(3R,4R)-3,4-dihydro, 3,4,8- trihdroxy, naphthalen-1(2H)-one (PS-11)}, {(4S) isosclerona (PS-12)}, furtermore PS-10 without structural characterization yet. The BDL-BD-28 days and 21 days extracts presented a chromatographic profile very similar to MPD-28 days extract, thus, the chromatographic fractionations of both extracts were targeted for isolation of substances absent in MPD-28 days. The 3,4 dihydoxy-benzoic acid was isolated just from the BD-extract 21 days, while the fractionation of the extract BDL 28days gave (PS-13 without structural characterization yet) as different. Among the isolated metabolites, {4-chromanone, 6-hydroxy-(S) -methyl- (PS-2)}, fusanolido B and PS10 (probably) showed were new compounds. The isolated compounds were shown to be inactive in cytotoxicity assays against strains of HCT-116 and MC-27 (breast adenocarcinoma). However, the 1- (2,5-dihydroxyphenyl) but-2-en-1-one showed strong inhibition with a MIC of 62.5 Âg/mL to be subjected to antimicrobial test against strains of fungi Candida Krusei (ATCCÂ 142432TM) and Candida albicans (ATCCÂ 10231TM) and CIM of 125 Âg/mL against Candida parapsilosis (ATCCÂ 22019TM), while {4-chromanone, 6-hydroxy-(S) -methyl-}, Z-3-(3-hydroxyphenyl) propenoate methyl, modiolide A, estagonolide E, fusanolido B and 3R,4R-dihydro-3,4,8-trihydroxy-1-(2H) -naftalelone showed moderate activity with MIC of 500 Âg / mL.Usual chromatographic techniques including liquid-liquid partitioning, flash chromatography and high pressure liquid chromatography (HPLC) were used for the isolation of secondary metabolites, while the structural characterization was possible through the use of spectrometric techniques using infrared (IR), mass spectrometry (MS), and uni and bidimensional techniques of nuclear magnetic resonance (NMR), and comparison with literature data.
Periconia hipidula à um fungo endofÃtico isolado de folhas secas provenientes de dunas do semiÃrido do estado da Bahia. O fungo foi submetido ao cultivo atravÃs da variaÃÃo de fatores nutricionais em quatro meios diferentes: MPD (malte, peptona e dextrose), BD (batata, dextrose), BDL (batata, dextrose e levedura) e MntPL (manitol, peptona e levedura), e anÃlise dos extratos em diferentes dias de incubaÃÃo (7, 14, 21, 28 dias). A prospecÃÃo da atividade citotÃxica preliminar foi realizada a partir dos extratos obtidos frente à linhagem de cÃlulas tumorais de cÃncer de cÃlon (HCT-116). Os extratos MPD â 28 dias, BDL - 28 dias e BD - 21 dias apresentaram uma atividade citotÃxica promissora e foram preliminarmente selecionados para o estudo quÃmico. O fracionamento cromatogrÃfico do extrato MPD-28 dias, resultou no isolamento de 11 metabÃlitos secundÃrios caracterizados como {(R), 6-hidroxi-2-metil, 4-cromanona (PS-1)}, { (S), 6-hidroxi-2-metil, 4-cromanona (PS-2)}, {E, 1-(2,5 diidroxi-fenil) but-2-en-1-ona (PS-3)}, {1-(2, 5 diidroxi-fenil)-butan-1-ona (PS-4)}, Z-3-(3 hidroxifenil) propenoato de metila (PS-5), modiolido A (PS-7), fusanolido B (PS-8), estagonolido E (PS-9), {(3R,4R)-3,4diidro,3,4,8 triidroxi,naftalen-1-(2H)-ona (PS-11)}, (4S)-isosclerona (PS-12), alÃm de PS-10 que se encontram em fase de caracterizaÃÃo estrutural. Os extratos BDL-28 dias e BD-21 dias apresentaram um perfil cromatogrÃfico bastante semelhante ao extrato MPD-28 dias, desta forma, os fracionamentos cromatogrÃficos de ambos os extratos foram direcionados para o isolamento de substÃncias ausentes em MPD-28 dias. O Ãcido 3,4 diidroxi-benzÃico (PS-6) foi isolado apenas do extrato BD-21 dias, enquanto que o fracionamento do extrato BDL 28d forneceu PS-13 (em fase de caracterizaÃÃo estrutural) como diferente. Dentre os metabÃlitos isolados, os compostos (2S)-6-hidroxi-2-metil-4-cromanona, fusanolido B apresentaram carÃter inÃdito na literatura. Os compostos isolados mostraram-se inativos em ensaios de atividade citotÃxica frente a cepas de HCT-116 e MC-27 (adenocarcinoma de mama). No entanto, o composto 1-(2,5-diidroxifenil)-but-2-en-1-ona apresentou elevada inibiÃÃo com CIM de 62,5 Âg/mL ao ser submetido à ensaio antimicrobiano frente a cepas de fungos Candida Krusei (ATCC 142432TM) e Candida albicans (ATCC 10231TM) e 125 Âg/mL frente à Candida parapsilosis (ATCC 22019TM), enquanto que o (2R)-6-hidroxi-2-metil-4-cromanona, Z-3-(3-hidroxifenil)-propenoato de metila, o modiolido A, o estagonolido E, o fusanolido B e a 3,4-diidro- 3,4,8-triidroxi-1(2H)-naftalelona apresentaram moderada atividade com CIM de 500 Âg/mL. TÃcnicas cromatogrÃficas usuais, incluindo partiÃÃo lÃquido-lÃquido, coluna de sÃlica flash e cromatografia de alta eficiÃncia (CLAE) foram utilizadas para o isolamento dos metabÃlitos secundÃrios, enquanto que a caracterizaÃÃo estrutural foi possÃvel atravÃs do uso de tÃcnicas espectromÃtricas utilizando infravermelho (IV), espectrometria de massa (EM) e ressonÃncia magnÃtica nuclear (RMN) com experimentos uni e bidimensionais, alÃm de comparaÃÃo com dados da literatura.
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Smith, D. L. "What does religious education achieve? : an investigation into the effect of secondary school pupils' experience of religious education on their attitude to religion." Thesis, University of Wales Trinity Saint David, 1999. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.683379.
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