Severe early onset preeclampsia: short and long term clinical, psychosocial and biochemical aspects

Preeclampsia is a pregnancy specific disorder commonly defined as de novo hypertension and proteinuria after 20 weeks gestational age. It occurs in approximately 3-5% of pregnancies and it is still a major cause of both foetal and maternal morbidity and mortality worldwide1. As extensive research has not yet elucidated the aetiology of preeclampsia, there are no rational preventive or therapeutic interventions available. The only rational treatment is delivery, which benefits the mother but is not in the interest of the foetus, if remote from term. Early onset preeclampsia (<32 weeks’ gestational age) occurs in less than 1% of pregnancies. It is, however often associated with maternal morbidity as the risk of progression to severe maternal disease is inversely related with gestational age at onset2. Resulting prematurity is therefore the main cause of neonatal mortality and morbidity in patients with severe preeclampsia3. Although the discussion is ongoing, perinatal survival is suggested to be increased in patients with preterm preeclampsia by expectant, non-interventional management. This temporising treatment option to lengthen pregnancy includes the use of antihypertensive medication to control hypertension, magnesium sulphate to prevent eclampsia and corticosteroids to enhance foetal lung maturity4. With optimal maternal haemodynamic status and reassuring foetal condition this results on average in an extension of 2 weeks. Prolongation of these pregnancies is a great challenge for clinicians to balance between potential maternal risks on one the eve hand and possible foetal benefits on the other. Clinical controversies regarding prolongation of preterm preeclamptic pregnancies still exist – also taking into account that preeclampsia is the leading cause of maternal mortality in the Netherlands5 - a debate which is even more pronounced in very preterm pregnancies with questionable foetal viability6-9. Do maternal risks of prolongation of these very early pregnancies outweigh the chances of neonatal survival? Counselling of women with very early onset preeclampsia not only comprises of knowledge of the outcome of those particular pregnancies, but also knowledge of outcomes of future pregnancies of these women is of major clinical importance. This thesis opens with a review of the literature on identifiable risk factors of preeclampsia

Discutindo a educação ambiental no cotidiano escolar: desenvolvimento de projetos na escola formação inicial e continuada de professores

A presente pesquisa buscou discutir como a Educação Ambiental (EA) vem sendo trabalhada, no Ensino Fundamental e como os docentes desta escola compreendem e vem inserindo a EA no cotidiano escolar., em uma escola estadual do município de Tangará da Serra/MT, Brasil. Para tanto, realizou-se entrevistas com os professores que fazem parte de um projeto interdisciplinar de EA na escola pesquisada. Verificou-se que o projeto da escola não vem conseguindo alcançar os objetivos propostos por: desconhecimento do mesmo, pelos professores; formação deficiente dos professores, não entendimento da EA como processo de ensino-aprendizagem, falta de recursos didáticos, planejamento inadequado das atividades. A partir dessa constatação, procurou-se debater a impossibilidade de tratar do tema fora do trabalho interdisciplinar, bem como, e principalmente, a importância de um estudo mais aprofundado de EA, vinculando teoria e prática, tanto na formação docente, como em projetos escolares, a fim de fugir do tradicional vínculo “EA e ecologia, lixo e horta”.Facultad de Humanidades y Ciencias de la Educació

Reconstruction de muons cosmiques en collision et recherche de gluinos se désintégrant en stop-top dans l'expérience CMS au LHC

The CMS experiment (Compact Muon Solenoid), built on the ring of the LHC (Large Hadron Collider), is recording data from proton-proton collisions for 2 years now. The alignment between all layers of the tracker, the sub-detector of CMS allowing the reconstruction and the measurement of the momentum of charged particles, is made by using tracks of particles created during collisions and tracks created by the passage of cosmic muons through this sub-detector. A first part of the presentation will be dedicated to the reconstruction of the tracks of these cosmic muons during collisions. A new method, called regional cosmic reconstruction, was developed and implemented. The 69 % efficiency and the fake rate around 1 % allow to use these tracks for the alignment. The second part, dedicated to the analysis of collision data, will concern the search of particles predicted by a model of extension of the Standard Model, the Supersymmetry, in a particular scenario, the light Stop scenario. In the case of a strong mixing in the third generation of squarks, the stop, supersymmetric partner of the top quark, could be light. In the analysis developped during this thesis, we were interested in the case where the mstop < mtop. In the MSSM with R-parity conservation, the gluino would be created by pair and would decay in a stop squark and a top quark. Stop would decays in a c quark and a neutralino, the lightest supereymmetric particle of the model, stable and interacting weakly. No excess with regards to Standard Model predictions was observed in 40pb-1 of data recorded by CMS in 2010. The limits obtained at 95 % confidence level allow to exclude masses of stop until 175 GeV for masses of gluinos going up to 350 GeV and low differences of masses between stop and neutralino.L'expérience CMS (Compact Muon Solenoid), construite sur l'anneau du LHC (Large Hadron Collider), enregistre des données provenant des collisions proton-proton depuis 2 ans. L'alignement entre toutes les couches du trajectographe, sous-détecteur de CMS permettant la reconstruction et la mesure de l'impulstion des particules chargées, est effectué à l'aide de traces de particules créées lors de la collision et des traces créées par le passage de muons d'origine cosmique à travers ce détecteur. La première partie de ce livre sera dédiée à la reconstruction des traces de ces muons lors des collisions. Une nouvelle méthode, appelée reconstruction cosmique régionale, a été développée et mise en place. L'efficacité de 69% et le taux de faux de l'ordre de 1% permettent l'utilisation de ces traces pour l'alignement. La deuxième partie, portant sur l'analyse des données de collision, s'intéressera à la recherche de particules prédites par un modèle d'extension du Modèle Standard, la Supersymétrie, dans un scénario particulier, le scénario du Stop Léger. Dans le cas d'un fort mélange dans la troisième génération de squarks, le stop, partenaire supersymétrique du quark top, peut être léger. Dans l'analyse effectuée au cours de cette thèse, nous nous sommes intéressés au cas au mstop < mtop. Dans le MSSM avec conservation de la R-parité, le gluino serait formé par paire et se désintégrerait en un squark stop et un quark top. Le stop se désintégrerait quant-à-lui en un quark c et un neutralino, particule supersymétrique la plus légère du modèle, stable et interagissant faiblement. Aucun excès par rapport aux prédictions du Modèle Standard n'a été relevé en utilisant les 40pb-1 de données enregistrées par CMS en 2010. Les limites obtenues à 95% de niveau de confiance permettent d'exclure des masses de stop jusqu'à 175 GeV pour des masses de gluinos allant jusqu'à 350 GeV et des faibles différences de masses entre le stop et le neutralino

Regional reconstruction for muons during collisions and search for gluinos decaying in stop-top in the CMS experiment at the LHC

L'expérience CMS (Compact Muon Solenoid), construite sur l'anneau du LHC (Large Hadron Collider), enregistre des données provenant des collisions proton-proton depuis 2 ans. L'alignement entre toutes les couches du trajectographe, sous-détecteur de CMS permettant la reconstruction et la mesure de l'impulstion des particules chargées, est effectué à l'aide de traces de particules créées lors de la collision et des traces créées par le passage de muons d'origine cosmique à travers ce détecteur. La première partie de ce livre sera dédiée à la reconstruction des traces de ces muons lors des collisions. Une nouvelle méthode, appelée reconstruction cosmique régionale, a été développée et mise en place. L'efficacité de 69% et le taux de faux de l'ordre de 1% permettent l'utilisation de ces traces pour l'alignement. La deuxième partie, portant sur l'analyse des données de collision, s'intéressera à la recherche de particules prédites par un modèle d'extension du Modèle Standard, la Supersymétrie, dans un scénario particulier, le scénario du Stop Léger. Dans le cas d'un fort mélange dans la troisième génération de squarks, le stop, partenaire supersymétrique du quark top, peut être léger. Dans l'analyse effectuée au cours de cette thèse, nous nous sommes intéressés au cas au mstop < mtop. Dans le MSSM avec conservation de la R-parité, le gluino serait formé par paire et se désintégrerait en un squark stop et un quark top. Le stop se désintégrerait quant-à-lui en un quark c et un neutralino, particule supersymétrique la plus légère du modèle, stable et interagissant faiblement. Aucun excès par rapport aux prédictions du Modèle Standard n'a été relevé en utilisant les 40pb-1 de données enregistrées par CMS en 2010. Les limites obtenues à 95% de niveau de confiance permettent d'exclure des masses de stop jusqu'à 175 GeV pour des masses de gluinos allant jusqu'à 350 GeV et des faibles différences de masses entre le stop et le neutralinoThe CMS experiment (Compact Muon Solenoid), built on the ring of the LHC (Large Hadron Collider), is recording data from proton-proton collisions for 2 years now. The alignment between all layers of the tracker, the sub-detector of CMS allowing the reconstruction and the measurement of the momentum of charged particles, is made by using tracks of particles created during collisions and tracks created by the passage of cosmic muons through this sub-detector. A first part of the presentation will be dedicated to the reconstruction of the tracks of these cosmic muons during collisions. A new method, called regional cosmic reconstruction, was developed and implemented. The 69 % efficiency and the fake rate around 1 % allow to use these tracks for the alignment. The second part, dedicated to the analysis of collision data, will concern the search of particles predicted by a model of extension of the Standard Model, the Supersymmetry, in a particular scenario, the light Stop scenario. In the case of a strong mixing in the third generation of squarks, the stop, supersymmetric partner of the top quark, could be light. In the analysis developped during this thesis, we were interested in the case where the mstop < mtop. In the MSSM with R-parity conservation, the gluino would be created by pair and would decay in a stop squark and a top quark. Stop would decays in a c quark and a neutralino, the lightest supereymmetric particle of the model, stable and interacting weakly. No excess with regards to Standard Model predictions was observed in 40pb-1 of data recorded by CMS in 2010. The limits obtained at 95 % confidence level allow to exclude masses of stop until 175 GeV for masses of gluinos going up to 350 GeV and low differences of masses between stop and neutralin

Prostate cancer radiomics and the promise of radiogenomics

Prostate cancer exhibits intra-tumoral heterogeneity that we hypothesize to be the leading confounding factor contributing to the underperformance of the current pre-treatment clinical-pathological and genomic assessment. These limitations impose an urgent need to develop better computational tools to identify men with low risk of prostate cancer versus others that may be at risk for developing metastatic cancer. The patient stratification will directly translate to patient treatments, wherein decisions regarding active surveillance or intensified therapy are made. Multiparametric MRI (mpMRI) provides the platform to investigate tumor heterogeneity by mapping the individual tumor habitats. We hypothesize that quantitative assessment (radiomics) of these habitats results in distinct combinations of descriptors that reveal regions with different physiologies and phenotypes. Radiogenomics, a discipline connecting tumor morphology described by radiomic and its genome described by the genomic data, has the potential to derive "radio phenotypes" that both correlate to and complement existing validated genomic risk stratification biomarkers. In this article we first describe the radiomic pipeline, tailored for analysis of prostate mpMRI, and in the process we introduce our particular implementations of radiomics modules. We also summarize the efforts in the radiomics field related to prostate cancer diagnosis and assessment of aggressiveness. Finally, we describe our results from radiogenomic analysis, based on mpMRI-Ultrasound (MRI-US) biopsies and discuss the potential of future applications of this technique. The mpMRI radiomics data indicate that the platform would significantly improve the biopsy targeting of prostate habitats through better recognition of indolent versus aggressive disease, thereby facilitating a more personalized approach to prostate cancer management. The expectation to non-invasively identify habitats with high probability of housing aggressive cancers would result in directed biopsies that are more informative and actionable. Conversely, providing evidence for lack of disease would reduce the incidence of non-informative biopsies. In radiotherapy of prostate cancer, dose escalation has been shown to reduce biochemical failure. Dose escalation only to determinate prostate habitats has the potential to improve tumor control with less toxicity than when the entire prostate is dose escalated

Classification of suspicious lesions on prostate multiparametric MRI using machine learning

We present a radiomics-based approach developed for the SPIE-AAPM-NCI PROSTATEx challenge. The task was to classify clinically significant prostate cancer in multiparametric (mp) MRI. Data consisted of a "training dataset" (330 suspected lesions from 204 patients) and a "test dataset" (208 lesions/140 patients). All studies included T2-weighted (T2-W), proton density-weighted, dynamic contrast enhanced, and diffusion-weighted imaging. Analysis of the images was performed using the MIM imaging platform (MIM Software, Cleveland, Ohio). Prostate and peripheral zone contours were manually outlined on the T2-W images. A workflow for rigid fusion of the aforementioned images to T2-W was created in MIM. The suspicious lesion was outlined using the high b-value image. Intensity and texture features were extracted on four imaging modalities and characterized using nine histogram descriptors: 10%, 25%, 50%, 75%, 90%, mean, standard deviation, kurtosis, and skewness (216 features). Three classification methods were used: classification and regression trees (CART), random forests, and adaptive least absolute shrinkage and selection operator (LASSO). In the held out by the organizers test dataset, the areas under the curve (AUCs) were: 0.82 (random forests), 0.76 (CART), and 0.76 (adaptive LASSO). AUC of 0.82 was the fourth-highest score of 71 entries (32 teams) and the highest for feature-based methods

Automatic Detection of Prostate Tumor Habitats using Diffusion MRI

Abstract A procedure for identification of optimal Apparent Diffusion Coefficient (ADC) thresholds for automatic delineation of prostatic lesions with restricted diffusion at differing risk for cancer was developed. The relationship between the size of the identified Volumes of Interest (VOIs) and Gleason Score (GS) was evaluated. Patients with multiparametric (mp)MRI, acquired prior to radical prostatectomy (RP) (n = 18), mpMRI-ultrasound fused (MRI-US) (n = 21) or template biopsies (n = 139) were analyzed. A search algorithm, spanning ADC thresholds in 50 µm2/s increments, determined VOIs that were matched to RP tumor nodules. Three ADC thresholds for both peripheral zone (PZ) and transition zone (TZ) were identified for estimation of VOIs at low, intermediate, and high risk of prostate cancer. The determined ADC thresholds for low, intermediate and high risk in PZ/TZ were: 900/800; 1100/850; and 1300/1050 µm2/s. The correlation coefficients between the size of the high/intermediate/low risk VOIs and GS in the three cohorts were 0.771/0.778/0.369, 0.561/0.457/0.355 and 0.423/0.441/0.36 (p < 0.05). Low risk VOIs mapped all RP lesions; area under the curve (AUC) for intermediate risk VOIs to discriminate GS6 vs GS ≥ 7 was 0.852; for high risk VOIs to discriminate GS6,7 vs GS ≥ 8 was 0.952. In conclusion, the automatically delineated volumes in the prostate with restricted diffusion were found to strongly correlate with cancer aggressiveness

An Automated Multiparametric MRI Quantitative Imaging Prostate Habitat Risk Scoring System for Defining External Beam Radiation Therapy Boost Volumes

To develop a prostate tumor habitat risk scoring (HRS) system based on multiparametric magnetic resonance imaging (mpMRI) referenced to prostatectomy Gleason score (GS) for automatic delineation of gross tumor volumes. A workflow for integration of HRS into radiation therapy boost volume dose escalation was developed in the framework of a phase 2 randomized clinical trial (BLaStM).An automated quantitative mpMRI-based 10-point pixel-by-pixel method was optimized to prostatectomy GSs and volumes using referenced dynamic contrast-enhanced and apparent diffusion coefficient sequences. The HRS contours were migrated to the planning computed tomography scan for boost volume generation.There were 51 regions of interest in 12 patients who underwent radical prostatectomy (26 with GS ≥7 and 25 with GS 6). The resultant heat maps showed inter- and intratumoral heterogeneity. The HRS6 level was significantly associated with radical prostatectomy regions of interest (slope 1.09, r = 0.767; P < .0001). For predicting the likelihood of cancer, GS ≥7 and GS ≥8 HRS6 area under the curve was 0.718, 0.802, and 0.897, respectively. HRS was superior to the Prostate Imaging, Reporting and Diagnosis System 4/5 classification, wherein the area under the curve was 0.62, 0.64, and 0.617, respectively (difference with HR6, P < .0001). HRS maps were created for the first 37 assessable patients on the BLaStM trial. There were an average of 1.38 habitat boost volumes per patient at a total boost volume average of 3.6 cm.An automated quantitative mpMRI-based method was developed to objectively guide dose escalation to high-risk habitat volumes based on prostatectomy GS

Search for narrow resonances using the dijet mass spectrum in pp collisions at s√=8 TeV

Results are presented of a search for the production of new particles decaying to pairs of partons (quarks, antiquarks, or gluons), in the dijet mass spectrum in proton-proton collisions at s√=8  TeV. The data sample corresponds to an integrated luminosity of 4.0  fb−1, collected with the CMS detector at the LHC in 2012. No significant evidence for narrow resonance production is observed. Upper limits are set at the 95% confidence level on the production cross section of hypothetical new particles decaying to quark-quark, quark-gluon, or gluon-gluon final states. These limits are then translated into lower limits on the masses of new resonances in specific scenarios of physics beyond the standard model. The limits reach up to 4.8 TeV, depending on the model, and extend previous exclusions from similar searches performed at lower collision energies. For the first time mass limits are set for the Randall–Sundrum graviton model in the dijet channel