Дисертації: "Multi-Organ"

1

Mali, Shruti Atul. "Multi-Modal Learning for Abdominal Organ Segmentation." Thesis, KTH, Skolan för kemi, bioteknologi och hälsa (CBH), 2020. http://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-285866.

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Deep Learning techniques are widely used across various medical imaging applications. However, they are often fine-tuned for a specific modality and are not generalizable when it comes to new modalities or datasets. One of the main reasons for this is large data variations for e.g., the dynamic range of intensity values is large across multi-modal images. The goal of the project is to develop a method to address multi-modal learning that aims at segmenting liver from Computed Tomography (CT) images and abdominal organs from Magnetic Resonance (MR) images using deep learning techniques. In this project, a self-supervised approach is adapted to attain domain adaptation across images while retaining important 3D information from medical images using a simple 3D-UNet with a few auxiliary tasks. The method comprises of two main steps: representation learning via self-supervised learning (pre-training) and fully supervised learning (fine-tuning). Pre-training is done using a 3D-UNet as a base model along with some auxiliary data augmentation tasks to learn representation through texture, geometry and appearances. The second step is fine-tuning the same network, without the auxiliary tasks, to perform the segmentation tasks on CT and MR images. The annotations of all organs are not available in both modalities. Thus the first step is used to learn general representation from both image modalities; while the second step helps to fine-tune the representations to the available annotations of each modality. Results obtained for each modality were submitted online, and one of the evaluations obtained was in the form of DICE score. The results acquired showed that the highest DICE score of 0.966 was obtained for CT liver prediction and highest DICE score of 0.7 for MRI abdominal segmentation. This project shows the potential to achieve desired results by combining both self and fully-supervised approaches.

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2

Karlsson, Albin, and Daniel Olmo. "Multi-organ segmentation med användning av djup inlärning." Thesis, KTH, Medicinteknik och hälsosystem, 2020. http://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-277813.

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Medicinsk bildanalys är både tidskonsumerade och kräver expertis. I den härrapporten vidareutvecklas en 2.5D version av faltningsnätverket U-Net anpassadför automatiserad njuresegmentering. Faltningsnätverk har tidigare visatliknande prestation som experter. Träningsdata för nätverket anpassades genomatt manuellt segmentera MR-bilder av njurar. 2.5D U-Net nätverket tränades med64 st njursegmenteringar från tidigare arbete. Volymanalys på nätverketssegmenterings förslag av 38.000 patienter visade den mängden segmenteradevoxlar som inte tillhörde njurarna var 0,35 %. Efter tillägg av 56 st av vårasegmenteringar minskade det till 0.11 %, en reduktion av cirka 68 %. Det är enstor förbättring av nätverket och ett viktigt steg mot tillämpning avautomatiserad segmentering.
Medical image analysis is both time consuming and requires expertise. In thisreport, a 2.5D version of the U-net convolution network adapted for automatedkidney segmentation is further developed. Convolution neural networks havepreviously shown expert level performance in image segmentation. Training datafor the network was created by manually segmenting MRI images of kidneys.The 2.5D U-Net network was trained with 64 kidney segmentations fromprevious work. Volume analysis on the network’s kidney segmentation proposalsof 38,000 patients showed that the ammount of segmented voxels that are notpart of the kidneys was 0.35%. After the addition of 56 of our segmentations, itdecreased to just 0.11%, indicating a reduction of about 68%. This is a majorimprovement of the network and an important step towards the development ofpractical applications of automated segmentation.

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3

Carrizo, Gabriel. "Organ Segmentation Using Deep Multi-task Learning with Anatomical Landmarks." Thesis, KTH, Skolan för kemi, bioteknologi och hälsa (CBH), 2018. http://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-241640.

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This master thesis is the study of multi-task learning to train a neural network to segment medical images and predict anatomical landmarks. The paper shows the results from experiments using medical landmarks in order to attempt to help the network learn the important organ structures quicker. The results found in this study are inconclusive and rather than showing the efficiency of the multi-task framework for learning, they tell a story of the importance of choosing the tasks and dataset wisely. The study also reflects and depicts the general difficulties and pitfalls of performing a project of this type.

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4

Jacobzon, Gustaf. "Multi-site Organ Detection in CT Images using Deep Learning." Thesis, KTH, Skolan för elektroteknik och datavetenskap (EECS), 2020. http://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-279290.

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When optimizing a controlled dose in radiotherapy, high resolution spatial information about healthy organs in close proximity to the malignant cells are necessary in order to mitigate dispersion into these organs-at-risk. This information can be provided by deep volumetric segmentation networks, such as 3D U-Net. However, due to limitations of memory in modern graphical processing units, it is not feasible to train a volumetric segmentation network on full image volumes and subsampling the volume gives a too coarse segmentation. An alternative is to sample a region of interest from the image volume and train an organ-specific network. This approach requires knowledge of which region in the image volume that should be sampled and can be provided by a 3D object detection network. Typically the detection network will also be region specific, although a larger region such as the thorax region, and requires human assistance in choosing the appropriate network for a certain region in the body. Instead, we propose a multi-site object detection network based onYOLOv3 trained on 43 different organs, which may operate on arbitrary chosen axial patches in the body. Our model identifies the organs present (whole or truncated) in the image volume and may automatically sample a region from the input and feed to the appropriate volumetric segmentation network. We train our model on four small (as low as 20 images) site-specific datasets in a weakly-supervised manner in order to handle the partially unlabeled nature of site-specific datasets. Our model is able to generate organ-specific regions of interests that enclose 92% of the organs present in the test set.
Vid optimering av en kontrollerad dos inom strålbehandling krävs det information om friska organ, så kallade riskorgan, i närheten av de maligna cellerna för att minimera strålningen i dessa organ. Denna information kan tillhandahållas av djupa volymetriskta segmenteringsnätverk, till exempel 3D U-Net. Begränsningar i minnesstorleken hos moderna grafikkort gör att det inte är möjligt att träna ett volymetriskt segmenteringsnätverk på hela bildvolymen utan att först nedsampla volymen. Detta leder dock till en lågupplöst segmentering av organen som inte är tillräckligt precis för att kunna användas vid optimeringen. Ett alternativ är att endast behandla en intresseregion som innesluter ett eller ett fåtal organ från bildvolymen och träna ett regionspecifikt nätverk på denna mindre volym. Detta tillvägagångssätt kräver dock information om vilket område i bildvolymen som ska skickas till det regionspecifika segmenteringsnätverket. Denna information kan tillhandahållas av ett 3Dobjektdetekteringsnätverk. I regel är även detta nätverk regionsspecifikt, till exempel thorax-regionen, och kräver mänsklig assistans för att välja rätt nätverk för en viss region i kroppen. Vi föreslår istället ett multiregions-detekteringsnätverk baserat påYOLOv3 som kan detektera 43 olika organ och fungerar på godtyckligt valda axiella fönster i kroppen. Vår modell identifierar närvarande organ (hela eller trunkerade) i bilden och kan automatiskt ge information om vilken region som ska behandlas av varje regionsspecifikt segmenteringsnätverk. Vi tränar vår modell på fyra små (så lågt som 20 bilder) platsspecifika datamängder med svag övervakning för att hantera den delvis icke-annoterade egenskapen hos datamängderna. Vår modell genererar en organ-specifik intresseregion för 92 % av organen som finns i testmängden.

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5

Hasal, Steven John 1965. "A model for the multi-organ metabolism and nephrotoxicity of chlorotrifluoroethylene." Diss., The University of Arizona, 1998. http://hdl.handle.net/10150/288818.

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During the past decade precision-cut tissue slices have begun to be utilized for toxicity and metabolism studies. These studies have primarily involved a single organ type. In this study, a new preparation of rat renal cortical slices was validated and used to investigate the toxicity of chlorotrifluoroethylene and its cysteine and glutathione conjugates. An additional level of complexity was added by utilizing a sequential incubation system in which rat renal cortical slices were directly incubated in the medium from liver slice incubations. Once the new renal slice preparation and sequential incubation system had been validated, these new methods were used to study the mechanism of toxicity of chlorotrifluoroethylene and it metabolites. The hypothesis being tested in these studies is that sequential biotransformation in the liver and the kidney is required for CTFE nephrotoxicity. In these studies I developed a sequential incubation system with precision-cut rat liver slices as the drug activating system and renal cortical slices as the target tissue for toxicity. Utilizing the sequential incubation system, I found that first incubating liver slices with CTFE and then transferring kidney slices to this liver slice incubation medium causes toxicity in the kidney slices. I also found that this toxicity correlates well with the toxicity observed with kidney slice incubations with the cysteine and glutathione conjugates of CTFE. By incubating slices with inhibitors of the various enzymes in the proposed metabolic pathway of CTFE, it was determined that glutathione conjugation in the liver and subsequent degradation by gamma-glutamyltranspeptidase are important steps in toxicity of CTFE. Although previous research with inhibitors of β-lyase have indicated that β-lyase is an essential enzyme in the bioactivation of CTFE, inhibition of the pyridoxal phosphate cofactor of this enzyme in renal slices did not reduce the toxicity of conjugates of CTFE. There was no reduction in toxicity when dipeptidases were inhibited when transport via the organic anion transporter or neutral amino acid transporter were inhibited. These data indicate that the glutathione conjugate of CTFE is formed in the liver and that the subsequent metabolism of this glutathione conjugate in the kidney is required for nephrotoxicity.

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6

Boussaid, Haithem. "Efficient inference and learning in graphical models for multi-organ shape segmentation." Thesis, Châtenay-Malabry, Ecole centrale de Paris, 2015. http://www.theses.fr/2015ECAP0002/document.

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Cette thèse explore l’utilisation des modèles de contours déformables pour la segmentation basée sur la forme des images médicales. Nous apportons des contributions sur deux fronts: dans le problème de l’apprentissage statistique, où le modèle est formé à partir d’un ensemble d’images annotées, et le problème de l’inférence, dont le but est de segmenter une image étant donnée un modèle. Nous démontrons le mérite de nos techniques sur une grande base d’images à rayons X, où nous obtenons des améliorations systématiques et des accélérations par rapport à la méthode de l’état de l’art. Concernant l’apprentissage, nous formulons la formation de la fonction de score des modèles de contours déformables en un problème de prédiction structurée à grande marge et construisons une fonction d’apprentissage qui vise à donner le plus haut score à la configuration vérité-terrain. Nous intégrons une fonction de perte adaptée à la prédiction structurée pour les modèles de contours déformables. En particulier, nous considérons l’apprentissage avec la mesure de performance consistant en la distance moyenne entre contours, comme une fonction de perte. L’utilisation de cette fonction de perte au cours de l’apprentissage revient à classer chaque contour candidat selon sa distance moyenne du contour vérité-terrain. Notre apprentissage des modèles de contours déformables en utilisant la prédiction structurée avec la fonction zéro-un de perte surpasse la méthode [Seghers et al. 2007] de référence sur la base d’images médicales considérée [Shiraishi et al. 2000, van Ginneken et al. 2006]. Nous démontrons que l’apprentissage avec la fonction de perte de distance moyenne entre contours améliore encore plus les résultats produits avec l’apprentissage utilisant la fonction zéro-un de perte et ce d’une quantité statistiquement significative.Concernant l’inférence, nous proposons des solveurs efficaces et adaptés aux problèmes combinatoires à variables spatiales discrétisées. Nos contributions sont triples: d’abord, nous considérons le problème d’inférence pour des modèles graphiques qui contiennent des boucles, ne faisant aucune hypothèse sur la topologie du graphe sous-jacent. Nous utilisons un algorithme de décomposition-coordination efficace pour résoudre le problème d’optimisation résultant: nous décomposons le graphe du modèle en un ensemble de sous-graphes en forme de chaines ouvertes. Nous employons la Méthode de direction alternée des multiplicateurs (ADMM) pour réparer les incohérences des solutions individuelles. Même si ADMM est une méthode d’inférence approximative, nous montrons empiriquement que notre implémentation fournit une solution exacte pour les exemples considérés. Deuxièmement, nous accélérons l’optimisation des modèles graphiques en forme de chaîne en utilisant l’algorithme de recherche hiérarchique A* [Felzenszwalb & Mcallester 2007] couplé avec les techniques d’élagage développés dans [Kokkinos 2011a]. Nous réalisons une accélération de 10 fois en moyenne par rapport à l’état de l’art qui est basé sur la programmation dynamique (DP) couplé avec les transformées de distances généralisées [Felzenszwalb & Huttenlocher 2004]. Troisièmement, nous intégrons A* dans le schéma d’ADMM pour garantir une optimisation efficace des sous-problèmes en forme de chaine. En outre, l’algorithme résultant est adapté pour résoudre les problèmes d’inférence augmentée par une fonction de perte qui se pose lors de l’apprentissage de prédiction des structure, et est donc utilisé lors de l’apprentissage et de l’inférence. [...]
This thesis explores the use of discriminatively trained deformable contour models (DCMs) for shape-based segmentation in medical images. We make contributions in two fronts: in the learning problem, where the model is trained from a set of annotated images, and in the inference problem, whose aim is to segment an image given a model. We demonstrate the merit of our techniques in a large X-Ray image segmentation benchmark, where we obtain systematic improvements in accuracy and speedups over the current state-of-the-art. For learning, we formulate training the DCM scoring function as large-margin structured prediction and construct a training objective that aims at giving the highest score to the ground-truth contour configuration. We incorporate a loss function adapted to DCM-based structured prediction. In particular, we consider training with the Mean Contour Distance (MCD) performance measure. Using this loss function during training amounts to scoring each candidate contour according to its Mean Contour Distance to the ground truth configuration. Training DCMs using structured prediction with the standard zero-one loss already outperforms the current state-of-the-art method [Seghers et al. 2007] on the considered medical benchmark [Shiraishi et al. 2000, van Ginneken et al. 2006]. We demonstrate that training with the MCD structured loss further improves over the generic zero-one loss results by a statistically significant amount. For inference, we propose efficient solvers adapted to combinatorial problems with discretized spatial variables. Our contributions are three-fold:first, we consider inference for loopy graphical models, making no assumption about the underlying graph topology. We use an efficient decomposition-coordination algorithm to solve the resulting optimization problem: we decompose the model’s graph into a set of open, chain-structured graphs. We employ the Alternating Direction Method of Multipliers (ADMM) to fix the potential inconsistencies of the individual solutions. Even-though ADMMis an approximate inference scheme, we show empirically that our implementation delivers the exact solution for the considered examples. Second,we accelerate optimization of chain-structured graphical models by using the Hierarchical A∗ search algorithm of [Felzenszwalb & Mcallester 2007] couple dwith the pruning techniques developed in [Kokkinos 2011a]. We achieve a one order of magnitude speedup in average over the state-of-the-art technique based on Dynamic Programming (DP) coupled with Generalized DistanceTransforms (GDTs) [Felzenszwalb & Huttenlocher 2004]. Third, we incorporate the Hierarchical A∗ algorithm in the ADMM scheme to guarantee an efficient optimization of the underlying chain structured subproblems. The resulting algorithm is naturally adapted to solve the loss-augmented inference problem in structured prediction learning, and hence is used during training and inference. In Appendix A, we consider the case of 3D data and we develop an efficientmethod to find the mode of a 3D kernel density distribution. Our algorithm has guaranteed convergence to the global optimum, and scales logarithmically in the volume size by virtue of recursively subdividing the search space. We use this method to rapidly initialize 3D brain tumor segmentation where we demonstrate substantial acceleration with respect to a standard mean-shift implementation. In Appendix B, we describe in more details our extension of the Hierarchical A∗ search algorithm of [Felzenszwalb & Mcallester 2007] to inference on chain-structured graphs

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7

Allen, Elizabeth Jane. "Multi-organ rheumatological disease : statistical analysis of outcome measures and their interrelationships." Thesis, University College London (University of London), 2004. http://discovery.ucl.ac.uk/1446556/.

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Idiopathic inflammatory myopathies are usually regarded as a heterogeneous group of autoimmune rheumatic diseases. Dermatomyositis and polymyositis may affect children and adults and, although rare, are a major cause of disability. In order to assess the value of conventional and newer therapies, a core set of measures for assessing myositis outcomes are being developed . This thesis reports on the design and analysis of two real patient exercises carried out to study proposed measures. An approach to the study of reliability and agreement is presented. Inference procedures for ratios of standard errors are developed. The myostitis measures are based on previous work in systemic lupus erythematosus (lupus), a major autoimmune rheumatic disease. International attempts to define validated disease activity and damage indices to assess patients with lupus have provided a consistent way to assess the disease. However, its multiple clinical manifestations prove a great challenge to rheumatologists managing patients with lupus. There is a need to better understand predictors of disease activity in order to improve and standardize therapy and to prevent the development of chronic damage. This thesis presents an analysis of a clinical database for patients with lupus. The aim is to develop approaches to examine the interrelationships between disease activity in the different organ systems. The database available for analysis consists of data collected on 440 patients over a period of 10 years. The analysis is based on logistic regression methodology with outcomes defined at the times of clinic visits. The usefulness of separate logistic regressions with dynamic covariates for the analysis of multinomial panel data is illustrated. The efficiency of the approach relative to modelling disease activity in continuous time is investigated.

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8

Millar, Benjamin John Minford. "The role of the formyl-peptide receptor in multi-organ fibrosis mechanisms." Thesis, University of Newcastle upon Tyne, 2016. http://hdl.handle.net/10443/3500.

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Mitochondrial Damage-associated molecular patterns (mtDAMPs) are an emerging source of endogenous alarmins. N-formylated peptides bind members of the formyl-peptide receptor (FPR) family. From its original role in chemotaxis of immune cells towards sites of infection the part that this G-protein coupled receptor (GPCR) plays in the human body is expanding with expression evident in cells of non-phagocyte origin as well as neutrophils and macrophage. To investigate how FPR1 affects the development of pulmonary fibrosis the bleomycin acute injury in vivo model was employed as its pathogenesis shares features with Idiopathic pulmonary fibrosis (IPF). Transgenic mice lacking functional fpr1 displayed a reduced inflammatory profile and fibrotic phenotype at acute and end-stage endpoints respectively post-bleomycin instillation. In vivo models of fibrosis in different organs such as the liver and kidney there was not the same protective effect with deletion of fpr1 as with acute bleomycin lung injury mechanism. This in turn brought the pathogenesis of the in vivo models into question particularly due to the abundance of fpr1 expression on neutrophils, the first line of defense of the immune system. By depleting neutrophils prior to the bleomycin injury the nature of these myeloid cells in this lung fibrosis model and through evaluation of the inflammatory and fibrotic phases post-instillation it is evident that these cells play a major role in how the disease develops. Translation to the human disease (IPF) was a vital step to elucidate the true role of FPR1 in chronic fibrosis mechanisms. Expression was demonstrated by immunofluorescence in CD45+ leukocytes as well as in isolated fibroblasts. This was corroborated by mRNA levels in primary cultured cells when FPR1 expression was ‘primed’ by inflammatory stimuli such as lipopolysaccharide (LPS). With effects observed in a murine setting and also in primary tissue/cells the FPR1 effect may be microenvironment/neutrophil dependent.

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9

Samarakoon, Prasad. "Random Regression Forests for Fully Automatic Multi-Organ Localization in CT Images." Thesis, Université Grenoble Alpes (ComUE), 2016. http://www.theses.fr/2016GREAM039/document.

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La localisation d'un organe dans une image médicale en délimitant cet organe spécifique par rapport à une entité telle qu'une boite ou sphère englobante est appelée localisation d'organes. La localisation multi-organes a lieu lorsque plusieurs organes sont localisés simultanément. La localisation d'organes est l'une des étapes les plus cruciales qui est impliquée dans toutes les phases du traitement du patient à partir de la phase de diagnostic à la phase finale de suivi. L'utilisation de la technique d'apprentissage supervisé appelée forêts aléatoires (Random Forests) a montré des résultats très encourageants dans de nombreuses sous-disciplines de l'analyse d'images médicales. De même, Random Regression Forests (RRF), une spécialisation des forêts aléatoires pour la régression, ont produit des résultats de l'état de l'art pour la localisation automatique multi-organes.Bien que l'état de l'art des RRF montrent des résultats dans la localisation automatique de plusieurs organes, la nouveauté relative de cette méthode dans ce domaine soulève encore de nombreuses questions sur la façon d'optimiser ses paramètres pour une utilisation cohérente et efficace. Basé sur une connaissance approfondie des rouages des RRF, le premier objectif de cette thèse est de proposer une paramétrisation cohérente et automatique des RRF. Dans un second temps, nous étudions empiriquement l'hypothèse d'indépendance spatiale utilisée par RRF. Enfin, nous proposons une nouvelle spécialisation des RRF appelé "Light Random Regression Forests" pour améliorant l'empreinte mémoire et l'efficacité calculatoire
Locating an organ in a medical image by bounding that particular organ with respect to an entity such as a bounding box or sphere is termed organ localization. Multi-organ localization takes place when multiple organs are localized simultaneously. Organ localization is one of the most crucial steps that is involved in all the phases of patient treatment starting from the diagnosis phase to the final follow-up phase. The use of the supervised machine learning technique called random forests has shown very encouraging results in many sub-disciplines of medical image analysis. Similarly, Random Regression Forests (RRF), a specialization of random forests for regression, have produced the state of the art results for fully automatic multi-organ localization.Although, RRF have produced state of the art results in multi-organ segmentation, the relative novelty of the method in this field still raises numerous questions about how to optimize its parameters for consistent and efficient usage. The first objective of this thesis is to acquire a thorough knowledge of the inner workings of RRF. After achieving the above mentioned goal, we proposed a consistent and automatic parametrization of RRF. Then, we empirically proved the spatial indenpendency hypothesis used by RRF. Finally, we proposed a novel RRF specialization called Light Random Regression Forests for multi-organ localization

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10

Olde, Damink Stephanus Wilibrordus Maria Jalan Rajiv. "Pathophysiological basis of hepatic encephalopathy: a multi-organ perspective in patients with liver failure." Maastricht : Maastricht : Universiteit Maastricht ; University Library, Maastricht University [Host], 2005. http://arno.unimaas.nl/show.cgi?fid=6361.

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11

Osabutey, Casmiel K. "The pathophysiology of sepsis-induced multi-organ dysfunction in a clinically relevant rat model." Thesis, St George's, University of London, 2007. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.582566.

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INTRODUCTION: Systemic sepsis occurs in 20-50 % of patients admitted to non-cardiac intensive care units and despite management, continues to be a serious clinical challenge. Development of novel therapeutic strategies is hampered by lack of an animal model which accurately and reproducibly mimics the clinical condition. AIMS: To refine a rat model of caecal ligation and puncture (CLP) induced sepsis; to investigate the effect of CLP on the structure of selected regions of the central and peripheral nervous system; to investigate the effect of CLP on structure and function of the gastrointestinal tract. METHODS: Under anaesthesia, the caecum was either ligated below the ileocaecal valve and punctured or only mobilised and the animals were allowed to recover for 18- 20 hours, during which time the following parameters were investigated: bacteraemia; locomotor activity; food and water intake; body weight; core temperature; serum lactate and glucose; white blood cell and platelet cell counts. The spinal cord, sciatic nerves and gut tissues were taken for quantitative and qualitative analysis using light microscopy. The above parameters were also investigated in a group of un-operated rats. In vitro studies were performed to compare the spontaneous and evoked contractile activity of the stomach, duodenum, colon and hepatic portal vein from either CLP or sham CLP animals. RESULTS: CLP but not sham CLP induced bacteraemia, lethargy (depressed nocturnal locomotor activity), anorexia, gastric retention, weight loss, pyrexia (within 4-5 hours) followed by hypothermia (from 17 hours), leucopaenia, thrombocytopaenia and hypoglycaemia after 18-20 hours. CLP also induced injury to the spinal cord and sciatic nerve characterised by peri-vascular oedema and myelin sheath swelling. There was massive mucosal sloughing, mucosal haemorrhage and vascular congestion in the gut tissue, indicative of gastrointestinal dysfunction in CLP but not in sham CLP rats. No significant differences were found between un-operated and sham CLP animals. Although CLP inflicted severe damage to the gut mucosa and inflammatory cell infiltration of the muscle layers, gastric, duodenal, colonic and hepatic portal vein tissue exhibited spontaneous contractile activity, although generally at a frequency lower than in sham CLP animals and with an elevated baseline tone. In addition, tissues were still capable of responding to a range of pharmacological agonists including acetylcholine, 5- hydroxytryptamine, phenylephrine and thrombin although the responses were modified in CLP animals. CONCLUSION: The spectrum of functional and histopathological changes described in the current study following CLP in the rat are consistent with the development of multi-organ dysfunction syndrome observed in patients with sepsis and argue that the refined model described is more clinically relevant for investigation of novel therapies than other models (e.g. LPS infusion). The results allow a reduction in the number of animals used by obviating the need for an un-operated group and permit the reduction of the post-CLP observation time required to obtain valid pathological results compared to previous investigations. The pathological changes observed in the spinal cord and sciatic nerve following CLP could explain the acute myelopathy and critical illness polyneuropathy that frequently occur following sepsis. The in vitro gut studies provide an insight into the mechanism(s) underlying gut dysfunction observed in patients with sepsis and show that despite severe damage the gut is likely to retain its capacity to respond to prokinetic drugs which could be used to treat motor disorders. These findings raise the possibility of identifying therapeutic interventions to restore neural and gastrointestinal tract function to normal and promote patients recovery

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12

Golfieri, Lucia <1980&gt. "The biopsychosocial approach in liver and multi-organ transplantation: assessment of the outcome predictors." Doctoral thesis, Alma Mater Studiorum - Università di Bologna, 2020. http://amsdottorato.unibo.it/9172/1/TESI%20PHD%20GOLFIERI.pdf.

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Introduction: During all phases of Liver Transplant (LT) process patients tend to develop psychological distress. Aims of the present study were to evaluate psychological variables at the time of evaluation for listing for LT (T0) and enter in the waitlist for LT (T1). Methods: We prospectively enrolled patients admitted at the Bologna Transplant Center between 2017 and 2018. Patients were compared with an age- and gender- matched control group. Significant differences between variables were estimated with non-parametric tests. χ2 or Fisher’s exact test was used for categorical variables while Mann-Whitney for continuous ones. Changes between T0 and T1 were analyzed with Wilcoxon Test. A p value less than 0.05 was pondered as noteworthy for all tests. Results: We enrolled 50 patients mainly males (68%) with mean age of 57±7 years. A DSM 5 diagnosis was present in one fifth of patients and DCPR syndrome in 44%. Enrolled subjects at T0 showed anxiety, depression and somatic symptoms. In comparison with control group, experimental one displayed lower scores in PCS and MCS of SF-12 (p=0.000, p=0.000, respectively), BC positive refraining, venting, instrumental support, humor, behavioural disengagement, emotional support, self-blame (all p<0.05) and in ISEL and PTG Scale (all p=0.000). Experimental group reported higher scores in the scale of SQ about anxiey, depression, somatic symptom and BC substance use score (all p<0.05). Twenty-five patients were admitted in the waitlist (T1). From T0 to T1, there was an increase of DSM-5 and DCPR diagnosis. At T1 in comparison with T0, we registered higher scores in SQ Hostility subscale (p=0.084) and BC Self distraction (p=0.079). Conclusions: Patients in screening for LT show many psychological disorders, often more pronounced than general population. From screening to enter into waitlist, many psychological patterns tend to worsen. Psychological support and multidisciplinary view might be useful during the transplant process.

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13

Paakkola, T. (Teija). "Novel genetic causes and functional studies of severe neurological and multi-organ diseases in children." Doctoral thesis, University of Oulu, 2019. http://urn.fi/urn:isbn:9789529407712.

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Abstract Undefined severe neurological and multi-organ diseases are rare as single diseases, but as a group of diseases, they are responsible for significant morbidity, impaired quality of life and mortality, emphasizing the importance of neuroscience research and its translation into novel diagnostic and treatment strategies. Molecular karyotyping and whole-exome sequencing were used to identify three novel disease-causing genes, GLE1, NHLRC2 and MYH7B, in Northem Finnish families having children with undefined progressive neuromuscular diseases. Functional studies on GLE1, NHLRC2, and MYH7B were conducted in order to understand better the impact of these mutations. The studies revealed that the cellular localization of GLE1 was impaired due to a mutation in the coding gene. The NHLRC2 is involved in many biological processes and its dysfunction has a role in the development of a novel FINCA disease and in fibrosis. Furthermore, mutations in MYH7B in the myosin family have now been connected to encephalomyopathies. Mutations in GLE1, NHLRC2 and MYH7B are involved in encephalomyopathies and neurodegeneration, stressing the important role of these genes in normal psychomotor development Analyses of these previously uncharacterized disease-causing gene mutations provided new insights into the etiologies behind these diseases, representing a relevant starting point for resolving the pathomechanisms underpinning these disorders. The newly-discovered human disease-causing genes and the novel phenotypes of childhood onset neuromuscular diseases provide the possibility for offering the relevant families preclinical diagnostics and may be beneficial in the identification of similar clinical phenotypes all around the world
Tiivistelmä Yksittäiset, määrittelemättömät, vaikeat neurologiset monielinsairaudet ovat harvinaisia. Sen sijaan neurologisten ja monielinsairauksien alle ryhmittyvät taudit ovat merkittävä syy useisiin sairauksiin, jotka heikentävät elämänlaatua ja aiheuttavat kuolleisuutta. Tästä johtuen neurotieteiden tutkimus ja saatujen tulosten soveltaminen diagnostiikassa ja hoitomuotojen kehittämisessä on hyvin tärkeää. Molekyylikaryotyypitys- ja eksomisekvensointi-menetelmiä hyödynnettiin etsittäessä taudin syytä eteneville neuromuskulaarisairauksille pohjoissuomalaisissa perheissä. Tutkimuksessa tehtiin lisäksi funktionaalisia kokeita GLE1-, NHLRC2- ja MYH7B-proteiineilla, jotta ymmärrettäisiin paremmin löydettyjen mutaatioiden vaikutus potilaiden sairauksiin. Havaittiin, että GLE1-mutaatio vaikutti proteiinin solunsisäiseen paikantumiseen. NHLRC2-proteiini puolestaan on mukana useissa solun biologisissa prosesseissa ja sen toiminnanhäiriö vaikuttaa FINCA-taudin ja fibroosin kehittymiseen. MYH7B-myosiinigeenimutaatio puolestaan yhdistettiin ensimmäistä kertaa enkefalomyopatiaan. Havaittujen tautigeenien; GLE1, NHLRC2 ja MYH7B, vaikutus enkefalomyopatioissa ja neurodegeneraatiossa kertoo, että kyseisillä geeneillä on hyvin todennäköisesti tärkeä rooli ihmisen kehityksessä. Kyseisten, aiemmin tuntemattomien sairautta-aiheuttavien geenimutaatioiden analysointi lisäsi tietoa sairauksien etiologiasta ja loi pohjan tautimekanismien ratkaisemiselle tulevaisuudessa. Työssä esitettyjä uusia sairautta-aiheuttavia geenejä ja uusia karakterisoituja lapsuusiän neuromuskulaarisairauksien ilmiasuja voidaan hyödyntää perheille tarjotun sikiödiagnostiikan lisäksi myös muiden potilaiden samankaltaisen taudinkuvan diagnosoinnissa maailmanlaajuisesti

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14

Tappenden, Kelly Anne. "Short-chain fatty acids enhance intestinal adaptation in rats receiving total parenteral nutrition, a multi-organ analysis." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1997. http://www.collectionscanada.ca/obj/s4/f2/dsk3/ftp04/nq21646.pdf.

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15

Hsu, Hao-Hsiang [Verfasser], and Ralf [Akademischer Betreuer] Pörtner. "Charakterisierung und numerische Simulation an Hautmodellen in einem Multi-Organ-Chip / Hao-Hsiang Hsu ; Betreuer: Ralf Pörtner." Hamburg : Universitätsbibliothek der Technischen Universität Hamburg-Harburg, 2019. http://d-nb.info/1200057791/34.

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16

Smith, Zaneta. "Hiding behind a mask : a grounded theory study of perioperative nurses’ experiences of participating in multi-organ procurement surgery." Thesis, Curtin University, 2012. http://hdl.handle.net/20.500.11937/1831.

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Multi-organ procurement surgical procedures are undertaken on donors who have consented at the time of their death to donate multiple organs, body parts or tissues. These donors fulfil the criteria for donation by either being certified as brain dead as a result of an injury or via a donation after cardiac death (DCD) pathway. Worldwide multi-organ procurement surgery has made a huge impact in both extending and enhancing the quality of life for recipient patients who have received organs from donors. Perioperative nurses working in surgical teams play a vital role in procuring organs from both paediatric and adult cadaver organ donors. The nature of the surgical procedure used for procuring organs, the urgency of coordinating surgical procurement teams and the removal of organs for urgent transplantation to awaiting recipients is fast paced and technical. The experience has been reported to evoke emotions which traumatically impact on perioperative nurses when assisting in these surgical procedures. There is currently a dearth of research examining the experiences of Australian perioperative nurses assisting within multi-organ procurement surgery.The objective of this study was to describe and gain a greater understanding of the personal experiences nurses encountered as part of their professional roles when involved in these surgical procedures. This thesis presents the substantive theory which has used a grounded theory methodology to describe the experiences of 35 perioperative nurses working within multi-organ procurement surgical teams from metropolitan, regional and rural hospitals in both New South Wales and Western Australia. The qualitative data from in-depth interviews were simultaneously collected and analysed to develop the substantive theory. The study findings draw attention to the complexities that exist for perioperative nurses to participate in these surgical procedures.The basic social psychological problem of hiding behind a mask was found to be a fundamental shared concern that the majority of perioperative nurses in this study faced when participating in multi-organ procurement surgery. The problem of hiding behind a mask was comprised of three stages: being unprepared, being overwhelmed and hiding the burden. The first stage, conceptualised as being unprepared, consisted of not knowing what to expect during the surgical procedure when they lacked prior knowledge and experience and felt unprepared for being exposed to death by operating on a cadaver donor and managing DCD donors within the operating room. Moreover participants were unprepared for witnessing the circumstances of each donor patient in addition to dealing with the grieving family.During the second stage participants described being overwhelmed with fears of facilitating death of the donor when they lacked understanding of the process of brain death diagnosis. They reported being overwhelmed at also having to witness the graphic nature of the procurement process and feeling overwhelmed by their own emotional responses to the donor’s death which they tried to hide and contain from their work colleagues through hiding behind a mask. Lastly the third stage of hiding behind a mask was identified as hiding the burden where participants were forced to contain their own personal beliefs and attitudes towards these surgical procedures whilst undertaking their professional roles. They reported hiding behind a mask when suppressing personal beliefs, hiding an objection to participate, not disclosing their own views or attitudes on death and spiritual ‘afterlife’ beliefs and lastly hiding not being able to cope when participating in these surgical procedures. The majority of the participants in this study articulated that various conditions influenced and directly contributed towards their experiences of hiding behind a mask. Three conditions were identified and these were reported as: work conditions, levels of knowledge and experience and levels of support.In an attempt to overcome the problem of hiding behind a mask, the data revealed that participants had to reach a turning point which was labelled as taking control. The turning point of taking control was described by participants as taking control of their own internal turmoil and rationalising the situation they were placed in whilst also changing their attitudes and thoughts towards their participation in the procedure. Once they had passed through the turning point of taking control participants were able to move beyond this point into the basic social psychological process of finding meaning.The basic social psychological process of finding meaning comprised of three stages: pushing through; preserving self and coming to terms. The first stage of finding meaning was conceptualised as pushing through. For many of the study participants in pushing through they dissociated themselves from their internal feelings and conflicts by focusing on the importance of their role and professional contributions towards the surgical procedure. The second stage of the basic social psychological process of finding meaning was conceptualised as preserving self, this saw participants implement strategies to protect themselves from both the traumatic experiences of procurement surgery and the tragic circumstances of the donors they came in contact with. Three aspects of preserving self were identified: being resilient; nurse self care and seeking personal support. The third and final stage of the basic social psychological process of finding meaning was conceptualised as coming to terms. During this stage participants were able to gain some understanding from their experiences by placing their participation role into perspective, honouring the donation wish and assisting in preserving life for the greater good when focusing on the needs of recipient patients requiring the organs they were assisting to procure. Conditions influencing the basic social psychological process of finding meaning encompassed: work conditions, levels of knowledge and experience and levels of support. Participants articulated these as positive influencing conditions such as a changing work environment, feeling less isolated and being supported by their work organisations.Throughout this thesis pertinent scientific literature has been woven into the research findings to illustrate the relevance of the newly developed theory and to place the substantive theory within the context of other findings and related theories to further support the trustworthiness of the current study data and the newly developed theory. The findings detailed in the substantive theory illustrate new contributions to the knowledge and understanding of the Australian perioperative nurses experiences when undertaking multi-organ procurement surgical procedures which will have relevance both nationally and internationally. The findings have implications and recommendations directed towards perioperative nurses, health services, perioperative organisations, government and policy makers.

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Ono, Masahiro. "Control of autoimmune myocarditis and multi-organ inflammation by GITR[high], Foxp3-expressing CD25[+] and CD25[-] regulatory T cells." Kyoto University, 2006. http://hdl.handle.net/2433/143877.

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18

Chen, Huiwen, Sean Thomas Mcphillips, and Vishnu Chundi. "Contralateral compartment syndrome inoculated by invasive group A streptococcus." TAYLOR & FRANCIS LTD, 2017. http://hdl.handle.net/10150/622921.

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Compartment syndrome is a rare but a well-documented complication in patients with trauma-induced group A streptococcus infection. Here, we present a case of a male who developed compartment syndrome on the left lower extremity after an injury inoculated by group A streptococcus on the right lower extremity. The patient was resuscitated with antibiotics, urgent fasciotomy, and immunoglobulin. The patient was eventually transferred to a burn center for further care.

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19

Seliger, Verena Ingeborg [Verfasser]. "Identification and evaluation of the predictive and diagnostic value of biomarkers applied to multi organ deficiencies in Cystic Fibrosis / Verena Ingeborg Seliger." Ulm : Universität Ulm. Medizinische Fakultät, 2014. http://d-nb.info/1047840588/34.

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20

Theobald, Jannick Florian [Verfasser], and Stefan [Akademischer Betreuer] Wölfl. "Entwicklung von mikrofluidischen Multi-Organ-Zellchipsystemen für die in vitro Metabolisierung und Bestimmung der Toxizität von Substanzen / Jannick Florian Theobald ; Betreuer: Stefan Wölfl." Heidelberg : Universitätsbibliothek Heidelberg, 2018. http://d-nb.info/1177253828/34.

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21

Theobald, Jannick Florian Verfasser], and Stefan [Akademischer Betreuer] [Wölfl. "Entwicklung von mikrofluidischen Multi-Organ-Zellchipsystemen für die in vitro Metabolisierung und Bestimmung der Toxizität von Substanzen / Jannick Florian Theobald ; Betreuer: Stefan Wölfl." Heidelberg : Universitätsbibliothek Heidelberg, 2018. http://nbn-resolving.de/urn:nbn:de:bsz:16-heidok-252159.

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22

Wagner, Ilka [Verfasser], Roland [Akademischer Betreuer] Lauster, Peter [Akademischer Betreuer] Neubauer, and Stetten Otto [Akademischer Betreuer] von. "Multi-organ-chip based skin models for research and substance testing / Ilka Wagner. Gutachter: Roland Lauster ; Peter Neubauer ; Otto von Stetten. Betreuer: Roland Lauster." Berlin : Technische Universität Berlin, 2014. http://d-nb.info/1066161968/34.

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23

Hing, Alfred Victor Chang Cardiac Research Institute Faculty of Medicine UNSW. "Optimising the quality of donor organs for transplantation: studies of hormone resuscitation of the brain-dead multi-organ donor and the development of a long-term preservation strategy to optimise function of the transplanted heart in a porcine model." Awarded by:University of New South Wales. Victor Chang Cardiac Research Institute, 2009. http://handle.unsw.edu.au/1959.4/44792.

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Brain death has adverse effects on the organ donor, increasing organ dysfunction and affecting transplantation outcomes. It can also render organs unsuitable for transplantation. Another determinant of organ quality is ischaemia-reperfusion injury, which limits ischaemic storage time for hearts to six hours. The aim of this thesis was to investigate the effectiveness of hormone resuscitation (HR) of the donor to ameliorate the effects of brain death. Another aim was to develop a donor management and organ preservation strategy to ameliorate the effects of ischaemia-reperfusion injury on the heart, thereby extending ischaemic preservation times. A porcine model of the brain-dead multi-organ donor with orthotopic cardiac transplantation was utilised. Donor HR was shown to improve cardiac contractility and haemodynamics, thereby reducing inotrope requirements. A follow-up study investigating the effects of three different donor management protocols demonstrated that donor haemodynamics, renal arterial flow and creatinine clearance were superior in HR animals compared with animals treated with noradrenaline or intravenous fluid alone. Noradrenaline was associated with a significant deterioration in pulmonary function (PaO2 and alveolar-arterial oxygen gradient) and a decline in donor pH. HR was not associated with any detrimental effects on the lungs, liver or pancreas compared with the other two groups. Preservation strategies incorporating glyceryl trinitrate (GTN) and cariporide, a Na+-H+ exchange inhibitor, were investigated to safely extend cardiac ischaemic preservation times. Pre-treatment with intravenous cariporide prior to heart explantation (donor) and reperfusion of the transplanted heart (recipient) was shown to effectively extend ischaemic time to 14 hours, evidenced by weaning off cardiopulmonary bypass. GTN and cariporide-supplemented Celsior, used as a cardioplegic/storage solution, was also effective in extending preservation time to 14 hours, with superior cardiac contractility compared with cariporide pre-treated hearts. Both treatments also ameliorated reperfusion injury, stabilising haemodynamics for up to three hours post-bypass. This thesis has demonstrated the effectiveness of HR to ameliorate the negative effects of donor brain death. It also provides evidence that combined GTN and cariporide-supplemented Celsior improves long-term preservation of the donor heart. These strategies offer the potential to increase the proportion of transplantable organs, to improve donor organ quality, and thereby improve transplantation outcomes.

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24

Materne, Eva-Maria [Verfasser], Roland [Akademischer Betreuer] Lauster, Jens [Akademischer Betreuer] Kurreck, and Horst [Akademischer Betreuer] Spielmann. "Generation of a multi-organ-chip-based liver equivalent for toxicity testing / Eva-Maria Materne. Gutachter: Roland Lauster ; Jens Kurreck ; Horst Spielmann. Betreuer: Roland Lauster." Berlin : Technische Universität Berlin, 2014. http://d-nb.info/1065669593/34.

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25

Gloger, Oliver [Verfasser]. "Combined Applications of the Level Set Method with Multi-Step Recognition and Refinement Algorithms for Fully Automatic Organ and Tissue Segmentation in MRI Data / Oliver Gloger." Greifswald : Universitätsbibliothek Greifswald, 2012. http://d-nb.info/1022617842/34.

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26

Hasenberg, Tobias [Verfasser], Roland [Akademischer Betreuer] Lauster, Uwe [Akademischer Betreuer] Marx, Eva-Maria [Akademischer Betreuer] Materne, Roland [Gutachter] Lauster, Peter [Gutachter] Neubauer, and Horst [Gutachter] Spielmann. "Emulating the human vasculature in a Multi-Organ-Chip platform : rheology and vasculogenesis / Tobias Hasenberg ; Gutachter: Roland Lauster, Peter Neubauer, Horst Spielmann ; Roland Lauster, Uwe Marx, Eva-Maria Materne." Berlin : Technische Universität Berlin, 2018. http://d-nb.info/1156331269/34.

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27

Madiedo-Podvršan, Sabrina. "Development of a lung-liver in vitro coculture model for the risk assessment of inhaled xenobiotics." Electronic Thesis or Diss., Compiègne, 2022. http://www.theses.fr/2022COMP2703.

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L’urbanisation et la mondialisation sont des phénomènes de société qui multiplient et complexifient les sources de pollution. Parmi elles, la pollution atmosphérique impacte notablement la santé humaine à l’échelle mondiale de par son caractère transfrontière. L’appareil respiratoire est une voie d’absorption de nombreux xénobiotiques, sous forme de gaz, d’aérosols ou de nanoparticules. Une fois dans les voies respiratoires, les substances inhalées sont susceptibles d’interagir avec les cellules pulmonaires. Les mécanismes par lesquels des xénobiotiques inhalés induisent des dommages pulmonaires sont complexes, notamment en raison de l’hétérogénéité cellulaire des poumons. En raison de cette complexité, les modèles animaux constituent un outil de référence pour les études toxicologiques prédictives, cependant, dans le contexte européen de réduction de l’expérimentation animale (REACH, et les règles 3R), le développement de méthodes alternatives fiables est devenu une nécessité. Les modèles in vitro sont de bons candidats car plus simple et moins couteux à mettre en oeuvre que les modèles vivo et permettent de travailler avec des cellules ou des tissus d’origine humaine ce qui contribue à améliorer la pertinence des résultats. Cependant, l’extrapolation limitée du vitro au vivo est souvent liée à un manque de complexité des modèles, notamment en raison de l’absence de communication inter-organes. Les technologies des multi-organes sur puce cherchent à surmonter ces limitations en connectant plusieurs organoïdes métaboliquement actifs au sein d’un même circuit de culture afin de reproduire des interactions de type systémiques. Dans ce contexte, nous décrivons un modèle permettant de connecter in vitro, par le biais de la microfluidique, une barrière pulmonaire (voie d’entrée des xénobiotiques inhalés) à un organe détoxifiant tel que le foie, afin d’évaluer la toxicité liée à un stress inhalatoire de façon plus systémique. Cette approche permet de considérer la biotransformation des composés inhalés et l’interaction inter-organes comme possible modulateurs de la toxicité. Le projet étant dans les premières phase de développement, la robustesse expérimentale était au coeur du projet. L’objectif principal était de prouver qu’une substance modèle était capable de transiter dans le dispositif, au travers des deux compartiments tissulaires, afin de pouvoir étudier la dynamique inter-organes poumon/foie en condition de stress xénobiotique. Le projet a été articulé en trois phases expérimentales : - Caractérisation des réponses biologiques spécifiques aux tissus pulmonaire et hépatique en réponse à un stress. La viabilité, la fonctionnalité et les activités métaboliques des monocultures ont été évaluées après exposition à une substance modèle. - Adaptation et préparation des monocultures aux conditions de co-culture afin de préserver la viabilité et la fonctionnalité des tissus. - Les compartiments pulmonaire et hépatique ont été cultivés jointement dans un circuit de culture microfluidique fermé. La co-culture a été exposée à une substance modèle à travers la barrière pulmonaire afin d’imiter un mode d’exposition inhalatoire. Les paramètres de viabilité et de fonctionnalité des tissus ont été évalué post-culture afin de mettre en évidence quelconque phénomène d’interaction inter-organe. La caractérisation du modèle de co-culture a été réalisé grâce à l’exposition d’un agent hépatotoxique de référence, largement étudié dans la littérature : l’acétaminophène aussi connu sous le nom de paracétamol (APAP). L’exposition à la barrière pulmonaire n’est pas physiologique mais permet d’observer quantitativement le passage et la circulation du xénobiotique à travers le dispositif car l’APAP interfère avec la viabilité et les performances métaboliques hépatique, permettant ainsi de vérifier que le compartiment hépatique peut avoir accès à l’exposition effectuée à travers la barrière pulmonaire
Urbanization and globalization are prevailing social phenomena that multiply and complexify the sources of modern pollution. Amongst others, air pollution has been recognized as an omnipresent life-threatening hazard, comprising a wide range of toxic airborne xenobiotics that expose man to acute and chronic threats. The defense mechanisms involved in hazardous exposure responses are complex and comprise local and systemic biological pathways. Due to this complexity, animal models are considered prime study models. However, in light of animal experimentation reduction (3Rs), we developed and investigated an alternative in vitro method to study systemic-like responses to inhalationlike exposures. In this context, a coculture platform was established to emulate interorgan crosstalks between the pulmonary barrier, which constitutes the route of entry of inhaled compounds, and the liver, which plays a major role in xenobiotic metabolism. Both compartments respectively comprised a Calu-3 insert and a HepG2/C3A biochip which were jointly cultured in a dynamically-stimulated environment for 72 hours. The present model was characterized using acetaminophen (APAP), a well-documented hepatotoxicant, to visibly assess the passage and circulation of a xenobiotic through the device. Two kinds of models were developed: (1) the developmental model allowed for the technical setup of the coculture, and (2) the physiological-like model better approximates a vivo environment. Based on viability, and functionality parameters the developmental model showed that the Calu-3 bronchial barrier and the HepG2/C3A biochip can successfully be maintained viable and function in a dynamic coculture setting for 3 days. In a stress-induced environment, present results reported that the coculture model emulated active and functional in vitro crosstalk that seemingly was responsive to high (1.5 and 3 mM) and low (12 and 24 μM) xenobiotic exposure doses. Lung/liver crosstalk induced modulation of stress response dynamics, delaying cytotoxicity, proving that APAP fate, biological behaviors and cellular stress responses were modulated in a broader systemic-like environment

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Guinin, Maxime. "Segmentation 3D des organes à risque du tronc masculin à partir d'images anatomiques TDM et IRM à l'aide de méthodes hybrides." Thesis, Normandie, 2017. http://www.theses.fr/2017NORMR019/document.

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Le cancer de la prostate est une cause majeure de décès dans le monde. La radiothérapie externe est une des techniques utilisée pour traiter ce cancer. Pour ce faire, la segmentation de la prostate et de ses organes à risque (OAR) associés (le rectum, la vessie et les têtes fémorales) est une étape majeure dans l’application du traitement. L’objectif de cette thèse est de fournir des outils afin de segmenter la prostate et les OAR de manière automatique ou semi-automatique. Plusieurs approches ont été proposées ces dernières années pour répondre à ces problématiques. Les OAR possédant un contraste relativement bon dans l’image, nous nous sommes orientés vers une approche semi-automatique de leur segmentation, consistant en une sur-segmentation de l’image en petites régions homogènes appelées superpixels. L’utilisateur de la méthode choisit ensuite de labelliser quelques superpixels dans les OAR comme des germes. Enfin, la méthode segmente les OAR grâce à une diffusion sur le graphe (à partir des germes) construit par des superpixels. Quant à la segmentation de la prostate, un sous-volume de l’image appelé VOI (Volume Of Interest), dans lequel se trouve la prostate, est tout d’abord défini. À l’intérieur de ce VOI, la segmentation de la prostate est réalisée. Un dictionnaire composé des caractéristiques de textures extraites sur chaque patch du VOI est d’abord construit. La sélection de caractéristiques du dictionnaire sous contraintes parcimonieuses permet ensuite de trouver celles qui sont le plus informatives. Enfin, basé sur ces caractéristiques sélectionnées, une propagation de label de patch sous contrainte parcimonieuse est appliquée pour segmenter la prostate à deux échelles, superpixels et pixels. Notre méthode a été évaluée sur des images TDM du Centre Henri Becquerel et IRM du challenge ISBI 2013 avec des résultats prometteurs
Prostate cancer is a leading cause of death worldwide. External radiotherapy is one of the techniques used to this disease. In order to achieve this, the segmentation of the prostate and its associated organs at risk (OAR) (rectum, bladder and femoral heads) is a major step in the application of the treatment. The objective of this thesis is to provide tools to segment prostate and OAR automatically or semi-automatically. Several approaches have been proposed in recent years to address these issues. As OAR have a relatively good contrast in the image, we have focused on a semi-automatic approach to segment them, consisting of an over-segmentation of the image into small homogeneous regions called superpixels. Then, the user labels some superpixels in the OAR as germs. Finally, the OAR segmentation is performed by a graph diffusion (from germs) constructed by superpixels. Regarding the prostate segmentation, a sub-volume of the image called VOI (Volume Of Interest), in which the prostate is located, is first defined. The prostate segmentation is performed within this VOI. A dictionary composed of the texture characteristics extracted on each patch of the VOI is first constructed. Then, the selection of characteristics of the dictionary under parsimonious constraints allows to find the most informative ones. Finally, based on these selected characteristics, patch label propagation under parsimonious constraint is applied to segment the prostate at two scales, superpixels and pixels. Our method was evaluated with promising results on TDM images of the Henri Becquerel Center and IRM of the 2013 ISBI challenge

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29

Kolam, Kerstin. "Lokala organ i Norden 1968-1986 : från idé till verklighet." Doctoral thesis, Umeå universitet, Statsvetenskapliga institutionen, 1987. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-67657.

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Neighbourhood councils are sub-municipal committees which operate within a geographically delimited area of a municipality or a municipal department. Their activities cover a single established policy area such as social services (single functioned committee) or several areas such as education, leisure, and social issues (multi-functioned committee). The thesis includes a comparative analysis of the origin, occurance, and performance of multi-functioned neighbourhood councils in Finland, Norway, and Sweden during the period 1968-1986. In the case of Denmark, the debate is analyzed and the question posed as to why neighbourhood councils were not introduced during this period.It is the interplay between a number of factors which determines how and why neighbourhood councils occur and in some cases endure and are developed further. The countries' traditions and characteristics - such as the size of the public sector and local government's share of it, size of municipalities, and political culture - are important in this context. Increased democracy and greater effectivity were the main aims of the reform and these have been achieved to some extent. The occurance of neighbourhood councils also means that participation, recruitment, articulation of demands, and communication between elector and elected are changed and somewhat improved. Where neighbourhood councils exist, greater consideration is given to geographical (rather than departmental) principles in the distribution and redistribution of services and welfare. Neighbourhood councils are clearly a source of further variation between and within the Nordic countries. It is, however, too early to judge whether the variation within countries will develop into inappropriate deviations from the principal of equal services for all or if they, on the contrary, are indications of greater future responsiveness.
digitalisering@umu

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30

Dunja, Mihajlović. "Dijagnostički i prognostički značaj markera disfunkcije endotela i poremećaja mehanizma hemostaze u sepsi." Phd thesis, Univerzitet u Novom Sadu, Medicinski fakultet u Novom Sadu, 2015. http://www.cris.uns.ac.rs/record.jsf?recordId=94104&source=NDLTD&language=en.

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Uvod: Sepsa je jedan od vodećih uzroka smrtnosti u jedinicama intenzivnog lečenja i van njih uprkos implementaciji novih dijagnostičkih i terapijskih protokola širom sveta. Multiorganska disfunkcija (MODS), koja predstavlja najtežu formu nepovoljnog toka sepse, je u osnovi svojih patofizioloških dešavanja obeležena promenama, koje se dešavaju na nivou kapilara, pre svega u endotelu. Poremećaji koagulacije koji se javljaju kao posledica ovih promena u endotelu su prepoznati kao jedan od dijagnostičkih kriterijuma prema najnovijim smernicama za dijagnostiku i lečenje sepse, međutim njihov značaj u predviđanju toka i ishoda ovog oboljenja još uvek nije precizno definisan. Cilj istraživanja: Odrediti koncentraciju markera endotelne aktivacije, aktivacije koagulacije, aktivnost prirodnih inhibitora koagulacije i funkcionalnost fibrinolize kod obolelih od sepse u odnosu na njihove vrednosti u zdravoj populaciji. Ispitati mogućnost upotrebe markera endotelne disfunkcije i pokazatelja poremećaja mehanizma hemostaze za postavljanje dijagnoze sepse i predikciju pojave komplikacija. Ispitati mogućnost upotrebe markera endotelne disfunkcije i pokazatelja poremećaja mehanizma hemostaze za procenu ishoda kod obolelih od sepse. Materijal i metode: Istraživanje je sprovedeno analitičkom metodom u formi studije preseka, a obuhvatilo je pacijente lečene na Odeljenju anestezije i reanimacije Urgentnog centra Kliničkog centra Vojvodine i na Klinici za infektivne bolesti Kliničkog centra Vojvodine, u Novom Sadu. Istraživanje je sprovođeno tokom 2012. i 2013. godine u trajanju od dve godine. U studiju je bilo uključeno 180 ispitanika od kojih je 150 imalo postavljenu dijagnozu sepse,a 30 ispitanika su činili kontrolnu grupu su klinički i biohemijski zdravih ispitanika, dobrovoljni davaoci krvi. Ispitanici su kategorisani u četiri grupe u odnosu na kliničko stanje i laboratorijske nalaze unutar prvih 24 časa od prijema: bolesnici sa sepsom, teškom sepsom, septičkim šokom i multiorganskom disfunkcijom na prijemu. Nakon kategorizacije ispitanika, izračunati su APACHE II i SOFA numerički pokazatelji procene težine bolesti ispitanika. U roku 24 časa od trenutka postavljanja dijagnoze sepse, iz uzoraka krvi ispitanika, izvršene su predviđene laboratorijske analize u cilju praćenja endotelne aktivacije, aktivacije koagulacije i inhibicije antikoagulantnih mehanizama. U toku 48 časova od prijema, bolesnici koji nisu imali MODS na prijemu su intenzivno praćeni u cilju evidentiranja razvoja multiorganske disfunkcije, dok su bolesnici koji su imali MODS praćeni radi evidentiranja perzistiranja ili eventualne rezolucije MODS-a. Zdravstveno stanje bolesnika je praćeno tokom 28 dana od trenutka uključivanja u studiju i nakon tog perioda je evidentiran ishod lečenja u smislu preživljavanja ili smrtnog ishoda. Statistička analiza je izvršena pomoću statističkog paketa IBM SPSS 20 Statistics. Podaci su predstavljeni tabelarno i grafički, a statistička značajnost određivana je na nivou p< 0,05. Rezultati: Vrednosti bioloških markera endotelne aktivacije i aktivacije koagulacije su statistički značajno povišene kod obolelih od sepse u odnosu na njihove vrednosti u zdravoj populaciji, dok su vrednosti prirodnih inhibitora koagulacije statistički značajno snižene kod obolelih od sepse u odnosu na njihove vrednosti u zdravoj populaciji. Vrednosti APTT-a, PT-a, D-dimera, fibrinogena, prirodnih inhibitora koagulacije i markera endotelne aktivacije (endokan i vWF antigena i aktivnosti) imaju značajan i veoma visok dijagnostički potencijal. Vrednosti biomarkera endotelne disfunkcije i pokazatelja poremećaja hemostaznog mehanizma su značajni prediktori komplikacija kod bolesnika sa sepsom. APTT, PT, D-dimer, broj trombocita, vrednosti priorodnih inhibitora koagulacije, trombomodulina, endokana i ETP-a su jednako validni u inicijalnoj proceni toka kliničke slike sepse kao i prediktivni APACHE II i SOFA skorovi. Koncentracija trombomodulina, D-dimera, ETP-a i PC su dobri prediktori nastanka MODS-a u prvih 48 časova u toku sepse. Endokan, PT, APTT, koncentracija fibrinogena, prirodnih inhibitora koagulacije i vrednosti ETP-a su značajni u predikciji mortaliteta kod bolesnika sa sepsom. Zaključci: Ukoliko bi pokazatelji aktivacije endotela i mehanizma hemostaze bili inkorporirani u određeni sistem skorovanja u cilju procene težine bolesti u smislu ishoda kod bolesnika sa sepsom, to bi moglo doneti doprinos boljoj klasifikaciji bolesnika, te primeni pravovremene i adekvatne terapije u cilju postizanja pozitivnog ishoda kod bolesnika sa sepsom. Prilikom interpretacije pokazatelja inflamacije i koagulacije neophodno je steći uvid u celokupnu sliku pro-i antikoagulantnih dešavanja koja se odvijaju tokom sepse, odnosno adekvatno proceniti pravac toka disbalansa mehanizma hemostaze da bi se eventualnim terapijskim merama mogao postići pozitivan učinak.
Introduction: Sepsis is one of the main causes of death in intensive care units and other hospital wards in spite of implementation of new sepsis treatment guidelines in everyday hospital practice worldwide. Changes that occur in the microvasculature, affecting primarily endothelial cell, are the basis of the pathophysiology of multiorgan dysfunction (MODS) in sepsis. Coagulation abnormalities which occur as a consequence of endothelial changes are recognized as diagnostic criteria for sepsis, but significance of these changes in the outcome prognosis and prediction of the course of sepsis is still not accurately defined. Aims: Evaluation of hemostasis related parameters and endothelial activation biomarkers values in patients with sepsis and healthy volunteers. Determination whether the levels of hemostasis-related parameters and biomarkers of endothelial activation have diagnostic significance and are they associated with MODS development and persistence in the first 48 hours of hospitalization and 28-day mortality in patients with sepsis. Material and methods: This is cross-sectional study conducted in 2012 and 2013 in the Department of Anesthesia and Reanimation at the Emergency Center of the Clinical Center of Vojvodina and in the Clinic of Infectious Disease at the Clinical Center of Vojvodina. 150 patients who fulfilled criteria for diagnosis of sepsis were included in the study. Patients were divided into 4 groups: sepsis, severe sepsis, septic shock and MODS. 30 healthy volunteers, blood donors were the control group. After the categorization of patients, during the first 24 hours of hospitalization, predictive APACHE II and SOFA scores were calculated. Hemostasis related parameters and endothelial activation biomarkers concentrations were determined within the first 24 hours of the onset of the disease. To assess the development of complication of the disease, patients were monitored for 48 hours for MODS development and persistence or resolution and for 28 days from the onset of sepsis for outcome assessment. Data were analyzed using SPSS 20.0 software and are presented in tables and graphs, statistical significance was set at p< 0,05. Results: Biomarkers of endothelial and coagulation activation are significantly higher in patients with sepsis in comparison to their values in healthy volunteers, while concentrations of natural anticoagulants are significantly lower in patients with sepsis than in healthy volunteers. APTT, PT, D-dimer, fibrinogen, natural anticoagulants and biomarkers od endothelial activation (endocan and vWF antigen and activity) have diagnostic significance in patients with sepsis. Hemostasis related parameters and endothelial activation biomarkers are good prognostic factors for complication development in patients with sepsis. APTT, PT, D-dimer, platelet count, natural anticoagulants, thrombomodulin, endocan and ETP are equally valuable in early prediction of sepsis development as APACHE II and SOFA scores. Thrombomodulin, D-dimer, ETP and PC are good predictors of MODS development during the first 48 hours from sepsis onset. Endocan, PT, APTT, fibrinogen concentration, values of natural anticoagulants and ETP values are significant in 28-day mortality prediction in patients with sepsis. Conclusion: A combination of markers of endothelial dysfunction with widely used ICU scores and organ failure assessment could contribute to an early recognition of complication development and consequent death in patients with sepsis. It is necessary to obtain the full insight in pro-and anticoagulant dynamic evaluation while interpreting coagulation and inflammation processes in sepsis development, in order to accurately lead early resuscitation therapy.

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Barbier, Emeline. "Étude des mécanismes physiopathologiques impliqués dans la toxicité des particules ultrafines chez un modèle murin : une approche multi-organes." Electronic Thesis or Diss., Université de Lille (2022-....), 2023. http://www.theses.fr/2023ULILS063.

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Bien qu'une diminution conséquente de la pollution atmosphérique soit constatée depuis les années 1990, cette dernière demeure un problème de santé publique majeur, à l'origine de plus de 4,2 millions de décès prématurés par an dans le monde. À l'heure actuelle, l'attention des experts se concentre sur les particules ultrafines (PM0,1 ou PUF) en raison de leur capacité à transloquer dans la circulation systémique pour atteindre les organes périphériques où elles seront alors susceptibles d'avoir un impact néfaste. Néanmoins, les connaissances en termes de mécanismes cellulaires et moléculaires impliqués dans la toxicité de ces particules restent encore très parcellaires et demeurent, le plus souvent, centrées sur leur cible principale qu'est le poumon. Ainsi, ce projet de thèse avait pour objectifs principaux d'apporter des éléments novateurs sur la toxicocinétique (i.e., distribution/persistance) et la toxicodynamique (i.e., mécanismes physiopathologiques, voies de signalisation associées) de PUF prélevées en milieu urbain, d'une part, et les effets organo-spécifiques des PUF et l'utilisation des miARN circulants comme indicateurs d'exposition chronique et/ou cumulées aux PUF dans un modèle murin, d'autre part. Afin de répondre à ces interrogations, des souris Balb/cJRj ont été exposées durant 3 mois à différentes doses de PUF prélevées dans la zone urbaine de Lille, puis des analyses ont été réalisés au sein de différents organes-cibles richement vascularisés, et par conséquent directement exposés aux PUF lors de leur phase de translocation et de distribution systémique. Les résultats obtenus ont démontré que, dans l'ensemble des organes cibles, le potentiel oxydant intrinsèque des PUF induisait indéniablement la production d'espèces pro-oxydantes et l'activation de défenses antioxydantes en quantité suffisante pour rétablir un état d'homéostasie redox mais ne parvenant pas, cependant, à éviter l'apparition d'une réponse inflammatoire au niveau pulmonaire, cardiaque et cérébral. Des approches transcriptomiques réalisés au sein des poumons, organes cibles présentant les effets délétères les plus marqués, ont suggéré la dérégulation de nombreuses voies de signalisation en relation avec les réponses oxydante et inflammatoire, qui constituent les mécanismes centraux de toxicité des PUF mais aussi avec des mécanismes de toxicité plus originaux tels que la dysfonction mitochondriale, la transition épithélio-mésenchymateuse et le remodelage tissulaire, dont la modulation a également été validée d'un point de vue fonctionnel. Ces données prometteuses pourraient à terme contribuer à une meilleure prise de décision quant à la réduction des émissions des PUF de même qu'à la réactualisation des normes réglementaires actuellement en vigueur
Although there has been a significant reduction in air pollution since the 1990s, it remains a major public health problem, responsible for over 4.2 million premature deaths worldwide every year. At present, experts' attention is focused on ultrafine particles (PM0.1 or UFP) because of their ability to translocate into the systemic circulation and reach peripheral organs, where they are likely to have a harmful impact. Nevertheless, the knowledge of the cellular and molecular mechanisms involved in the toxicity of these particles is still very patchy, and most often remains focused on their main target, the lung. Thus, the main objectives of this thesis project were to provide innovative insights into the toxicokinetics (i.e., distribution/persistence) and toxicodynamics (i.e., pathophysiological mechanisms, associated cell signaling pathways) of UFP collected in urban environments, on the one hand, and the organospecific effects of UFP and the use of circulating miRNA as indicators of chronic and/or cumulative exposure to UFP in a mouse model, on the other hand. To answer these questions, Balb/cJRj mice were exposed for 3 months to various doses of UFP collected in the urban area of Lille, then analyzed in various target organs richly vascularized, and therefore directly exposed to UFP during their translocation and systemic distribution phase. The results showed that, in all target organs, the intrinsic oxidative potential of UFP undeniably induced the production of oxidative oxygen species and the activation of antioxidant defenses in sufficient quantities to restore a state of redox homeostasis, but were unable to prevent the onset of an inflammatory response in the lungs, heart and brain. Transcriptomic approaches carried out in the lungs, the target organ with the most marked deleterious effects, have suggested the deregulation of numerous signaling pathways in relation to oxidative and inflammatory responses, which constitute the central mechanisms of UFP toxicity, but also with more original toxicity mechanisms such as mitochondrial dysfunction, epithelial-mesenchymal transition and tissue remodeling, whose modulation has also been validated from a functional point of view. These promising data could ultimately contribute to better decision-making on the reduction of UFP emissions, as well as to the updating of current regulatory standards

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32

Kollander, Barbro. "Inductively Coupled Plasma Atomic Emission Spectrometry : Exploring the Limits of Different Sample Preparation Strategies." Doctoral thesis, Uppsala universitet, Analytisk kemi, 2011. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-150861.

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This thesis describes two different sample preparation strategies for inductively coupled plasma atomic emission spectrometry (ICP-AES), and their ability regarding multi element quantification in complex samples. Sensitivity, repeatability, reproducibility and accuracy were investigated. The aim was to increase the over all efficiency, the speed of analysis, and/or the sensitivity of the analytical method. The intention was to measure analytes with concentrations ranging from ng/g to mg/g simultaneously. The aim was additionally to study chemical and physical processes occurring during the sample preparation, the sample transport to the plasma, and the atomization therein. In the first sample preparation strategy, a hydrophilic highly cross-linked iminodiacetate-agarose adsorbent, IDA-Novarose, was used for preconcentration of metal ions, and matrix elimination in natural water samples. The sorbent was synthesized with different binding capacities. The effect of the capacity on preconcentration, matrix elimination, and uptake capability at high flow rates was studied. For a high capacity IDA-Novarose (≥ 45 µmole/ml) quantitative uptake was seen even at high flow rates (100 ml/min) for Cu2+ with a high affinity to the adsorbent, and for Cd2+ with a moderate affinity. For lower capacities the uptake of Cd2+ was affected by the sample matrix and the flow rate. A method based on the determination of the conditional stability constant of the metal sorbent complex was suggested for the prediction of the sorbent capacity needed to obtain quantitative recovery and optimal matrix elimination. The sorbent was used in a flow system with online buffering for the analysis of a certified riverine water (SLRS-3), tap water and lake water. With few exceptions the results obtained by ICP-AES after preconcentration agreed well with the certified concentrations and results obtained by ICP-MS. The other sample preparation strategy discussed is a method for non digested biological samples from different animal organs for the multi element analysis by ICP-AES. This “mix and measure method” consists of a simple homogenization of the sample with a mixing rod in a small amount of neutral media, followed by dilution and direct measurement with ICP-AES. The total time of analysis is only a few minutes. The ability of this fast method to accurately quantify some elements of toxic, environmental, and/or physiological concern with the lowest possible sample dilution and the highest possible plasma load was evaluated. In 10 % liver slurry Cd, Co, and Sr, at concentration levels around 0.05 µg/g were quantified simultaneously with P and K around 2000 µg/g and with several other elements in between (Al, Ca, Cu, Fe, Mg, Mn, Pb, and Zn). The relative standard deviation of repeated measurements of samples was around 5 - 6 % for regardless of the concentration of the element. The method was also used for fast screening of the elemental distribution in mice organs (brain, heart, kidney, liver, lung and spleen).

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Huber, Adrian Thomas. "Multi-organ non-invasive tissue characterization of fibrosis, adipose tissue, edema and inflammation with magnetic resonance (MR) imaging : applications to myocardium, skeletal muscle and liver interactions Cardiac MR strain: a noninvasive biomarker of fibro-fatty remodeling of the left atrial myocardium Comparison of MR T1 and T2 mapping parameters to characterize myocardial and skeletal muscle involvement in systemic Idiopathic Inflammatory Myopathy (IIM) Non-invasive differentiation of acute viral myocarditis and idiopathic inflammatory myopathy with cardiac involvement using magnetic resonance imaging T1 and T2 mapping CT predicts liver fibrosis: Prospective evaluation of morphology- and attenuationbased quantitative scores in routine portal venous abdominal scans." Thesis, Sorbonne université, 2019. http://www.theses.fr/2019SORUS135.

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Cette thèse réalise une preuve de concept pour quantifier la déformation de l’oreillette gauche (OG) en IRM, ainsi que la relaxométrie IRM dans le myocarde, dans les muscles squelettiques et dans le foie. Grâce à l’interaction entre radiologues et ingénieurs, deux logiciels différents ont été développés, appliqués et validés pour l'analyse de la déformation myocardique multi-chambre et pour la cartographie quantitative du T1 multi-organes. La première publication a montré une forte corrélation de la déformation de l’OG, avec le degré de remplacement fibro-graisseux en histologie. Ce biomarqueur d'imagerie fonctionnelle est prometteur, puisque le remodelage structurel du myocarde est un substrat morphologique connu du dysfonctionnement électro-physiologique et de la fibrillation atriale. La deuxième publication a démontré l'influence de la composition et de la vascularisation de différents tissus sur les paramètres cartographiques T1. ΔT1 (prise de contraste musculaire relative) et EHF (prise de contraste musculaire normalisée par la prise de contraste dans le sang) ont été introduits comme alternatives simples au volume extracellulaire (ECV). Dans la troisième publication, les paramètres de relaxométrie appliqués aux muscles squelettiques ont permis une discrimination entre patients avec myocardite aiguë et patients avec des myosites systémiques. La quatrième publication a introduit le T1 du foie pour quantifier l’insuffisance cardiaque chez des patients avec des cardiomyopathies idiopathiques dilatées, montrant de meilleures performances que les paramètres fonctionnels établis tels que les volumes, la fraction d'éjection ou la déformation myocardique
This thesis provides a proof of concept for MR atrial strain, as well as MR relaxometry in the myocardium, in skeletal muscles and in the liver. Thanks to a close interaction between radiologist and software engineers, two different softwares were developed, applied and validated: one for multiorgan T1 mapping in the myocardium, skeletal muscle and liver, another one for cardiac four-chamber strain analysis and volumetry. The first publication showed a strong correlation of LA strain with the degree of fibro-fatty replacement in histology. Such functional imaging biomarker in combination with LA volumetry could help to guide clinical decisions, since myocardial structural remodeling is a known morphologic substrate of LA dysfunction, atrial fibrillation and adverse outcome. In the second publication, MR relaxometry parameters applied to the myocardium and skeletal muscles in IIM patients and healthy volunteers were used as a model to demonstrate influences of different tissue composition and vascularization on T1 mapping parameters. ΔT1 and EHF were introduced as simple alternatives to ECV in highly vascularized tissues such as the myocardium. In the third publication, MR relaxometry parameters applied to the skeletal muscls allowed for an accurate discrimination of AVM and IIM with cardiac involvement. However, when applied to the myocardium, parametric mapping did not separate between the two groups. The fourth publication introduced native T1 of the liver an easily accessible and accurate non-invasive imaging associate of congestive HF in IDCM patients with better performance than established functional parameters such as LV volumes, ejection fraction or strain

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Yi, Lin Chung, and 林忠義. "An Analysis of Organ Donation Legal System from Multi-perspectives：Focusing on Cadaveric Organ Donation." Thesis, 2003. http://ndltd.ncl.edu.tw/handle/11308875134591431784.

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碩士
國立交通大學
科技法律學程碩士班
91
According to Organ Procurement Association, R.O.C., 5000~6000 patients are in the waiting list of organ transplantation, but there are less than 100 donors a year in Taiwan. The organ donation rate is about 3pmp in Taiwan, less than west world 20pmp. Legal profession does not pay much attention to organ donation. Medical profession though discusses this subject a lot, they usually talk about promoting organ supply, no sharing. Medical profession puts utilitarianism in mind, not Kantianism. Many papers in medical profession talk about UNOS, but dismiss Spain the best in organ donation rate, they do not discuss the successful experience of bone marrow or blood donation in Taiwan, either. This thesis tries to examine organ donation problems through ethics, economic analysis of law, social analysis of law, comparative law, legal history, secondary material review, interview research. The purpose of this thesis is to suggest an appropriate organ donation legal system from introducing European and American organ donation system, and referring to the experience of bone marrow and blood donation in Taiwan. This thesis analyzes proposals from scholars, including organ donation from executed prisoners, organ market, future market, compensation system, presumed consent, mandated choice, mutual insurance pool, xenotransplantation, organ reproduction, for the goal of promoting organ supply. Because the public’s attitudes influence organ supply deeply, this thesis tries to find out the attitudes of public and medical profession from scholars’ survey reports, and also I interviewed 16 related persons. This thesis also discusses the legal history of Human Organ Transplant Act, the most important law in organ donation in Taiwan. This thesis suggests that organ donation system should base on Spain model, and adopt the experience of U.S. organ donation system, Taiwan’s bone marrow and blood donation system. In the near future, it will still be few of donative organs, so I think we must set up fair organ sharing principles in Taiwan. In addition, Human Organ Transplant Act needs to be reformed, in order to run organ donation legal system effectively. Of course, it is not enough just to reform Human Organ Transplant Act, we need to take suitable legal policies to promote organ supply under humanity and efficiency. This thesis proposes：giving up organ donation from executed prisoners, adopting compensation system, mandated choice, mutual insurance pool , encouraging the development of gene engineering and xenotransplantation technology , forbidding overseas organ sale , reforming the running of prosecutors’ autopsy.

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McDermott, Sean Patrick. "The role of syndecan-1 in multi-organ tumor resistance to chemical carcinogens." 2005. http://catalog.hathitrust.org/api/volumes/oclc/70821376.html.

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Josiah, M. Robina. "Evaluating the determinants of a successful organ donor process in a multi-hospital system." 2006. http://etda.libraries.psu.edu/theses/approved/WorldWideIndex/ETD-1501/index.html.

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37

Bagulho, Inês Correia. "Reference tissue normalization of prostate MRI with automatic multi-organ deep learning pelvis segmentation." Master's thesis, 2018. http://hdl.handle.net/10451/36792.

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Tese de mestrado integrado, Engenharia Biomédica e Biofísica (Engenharia Clínica e Instrumentação Médica) Universidade de Lisboa, Faculdade de Ciências, 2018
Prostate cancer is the most common cancer among male patients and second leading cause of death from cancer in men (excluding non-melanoma skin cancer). Magnetic Resonance Imaging (MRI) is currently becoming the modality of choice for clinical staging of localized prostate cancer. However, MRI lacks intensity quantification which hinders its diagnostic ability. The overall aim of this dissertation is to automate a novel normalization method that can potentially quantify general MR intensities, thus improving the diagnostic ability of MRI. Two Prostate multi-parametric MRI cohorts, of 2012 and 2016, were used in this retrospective study. To improve the diagnostic ability of T2-Weighted MRI, a novel multi-reference tissue normalization method was tested and automated. This method consists of computing the average intensity of the reference tissues and the corresponding normalized reference values to define a look-up-table through interpolation. Since the method requires delineation of multiple reference tissues, an MRI-specific Deep Learning model, Aniso-3DUNET, was trained on manual segmentations and tested to automate this segmentation step. The output of the Deep Learning model, that consisted of automatic segmentations, was validated and used in an automatic normalization approach. The effect of the manual and automatic normalization approaches on diagnostic accuracy of T2-weighted intensities was determined with Receiver Operating Characteristic (ROC) analyses. The Areas Under the Curve (AUC) were compared. The automatic segmentation of multiple reference-tissues was validated with an average DICE score higher than 0.8 in the test phase. Thereafter, the method developed demonstrated that the normalized intensities lead to an improved diagnostic accuracy over raw intensities using the manual approach, with an AUC going from 0.54 (raw) to 0.68 (normalized), and automatic approach, with an AUC going from 0.68 to 0.73. This study demonstrates that multi-reference tissue normalization improves quantification of T2-weighted images and diagnostic accuracy, possibly leading to a decrease in radiologist’s interpretation variability. It is also possible to conclude that this novel T2-weighted MRI normalization method can be automatized, becoming clinically applicable.

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38

Pratt, Mary Margaret. "Chlorophyllin chemoprevention against Dibenzo[a,l]pyrene-initiated multi-organ carcinogenesis in the rainbow trout model." Thesis, 2003. http://hdl.handle.net/1957/31143.

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Chlorophyllin (CHL), a water-soluble derivative of the green plant pigment, chlorophyll, is an effective antimutagen and anticarcinogen in various model systems when used as a modulator against a class of carcinogens that, in general, have a structure consisting of at least three fused rings. Dibenzo[a,l]pyrene (DBP), an extremely potent environmental carcinogen, has been isolated from urban air samples, tobacco smoke, and coal smoke condensate. A study was conducted to evaluate the complex interrelationships among dietary DBP doses with co-exposure to a range of CHL doses. In order to achieve adequate statistical power in the generation of multiple dose-response curves, this dose-dose matrix experiment utilized over 12,000 rainbow trout. The resulting DNA adducts were assessed and evaluated as biomarkers of exposure to discern their relationship with the final tumor outcome. CHL was highly effective in reducing DBP-initiated DNA adduct formation in the liver and stomach and strongly inhibited tumor formation in the liver (56-79% inhibition), stomach (30-68%), and swim bladder (over 80% at the highest DBP dose). Molecular dosimetry revealed adduct formation to be predictive of final tumor response in both organs regardless of CHL dose. Other parameters evaluated were consistent with CHL-mediated protection. A clinical CHL preparation, evaluated in a human population subsequent to the seminal demonstration of CHL chemopreventive properties against AFB�� in trout (1), revealed CHL to be just as effective in reducing biomarkers of alfatoxin exposure to humans (2). Dietary administration of this clinical preparation along with DBP in the rainbow trout demonstrated CHL protective capacity against DBP-initiated multi-organ DNA adduct formation and final tumor incidence. Sucrose was evaluated, deemed unlikely to be sequestered in a complex with CHL, and was used as a control in a pharmacokinetic study evaluating the biodistribution of DBP with and without CHL. The results provide evidence against a non-specific masking mechanism for CHL-mediated blocking of DBP (or aflatoxin)-initiated tumorigenesis. CHL at multiple doses provided significant protection against multi-dose DBP-initiated DNA adduction and tumor formation in multiple organs. CHL-mediated protection, primarily by reduced carcinogen biouptake and consistent with a complexation mechanism, is supported by these results.
Graduation date: 2003

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39

Chih-Wen, Yu, and 游智雯. "A study on the functional indicators construct of public relationship for house organ of the multi-level marketing industry." Thesis, 2010. http://ndltd.ncl.edu.tw/handle/90167765088201443312.

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40

Karam, Oliver. "Évaluation de l’effet clinique de la durée d’entreposage des culots érythrocytaires chez les enfants admis aux soins intensifs." Thèse, 2011. http://hdl.handle.net/1866/5021.

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Les transfusions de culots érythrocytaires (CE) sont un traitement fréquent en soins intensifs pédiatriques. Des études chez l’adulte suggèrent qu’une durée prolongée d’entreposage des CE est associée à une mauvaise évolution clinique. Aucune étude prospective n’a été conduite en pédiatrie. Notre objectif était d’évaluer l’effet clinique de la durée d’entreposage des CE chez des patients de soins intensifs pédiatriques. Nous avons donc conduit une étude observationnelle prospective dans 30 centres de soins intensifs pédiatriques en Amérique du Nord, chez tous les patients consécutifs de moins de 18 ans, séjournant aux soins intensifs pendant plus de 48 heures. Le critère de jugement primaire était l’incidence de cas de syndrome de défaillance multiviscérale après transfusion. Les critères de jugement secondaire étaient la mortalité à 28 jours et la durée d’hospitalisation aux soins intensifs. En utilisant un modèle de régression logistique, les risques relatifs furent ajustés pour le sexe, l’âge, la sévérité de la maladie à l’admission, le nombre total de transfusions et la dose totale de transfusion. L’étude a montré que les patients recevant des CE entreposés pendant 14 jours ou plus avaient un risque relatif ajusté de 1.87 (IC 95% 1.04 :3.27, p=0.03) de contracter ou de détériorer un syndrome de défaillance multiviscérale après transfusion. Ces mêmes patients avaient une durée d’hospitalisation aux soins intensifs prolongée (+3.7 jours, p<0.001), mais pas de risque augmenté de mortalité. En conclusion, chez les patients de soins intensifs pédiatriques, la transfusion de CE entreposés 14 jours ou plus est associée avec une augmentation de l’incidence de syndrome de défaillance multiviscérale et une durée d’hospitalisation prolongée aux soins intensifs.
Transfusion is a common treatment in pediatric intensive care units. Studies in adults suggest that prolonged storage of red blood cell units is associated with worse clinical outcome. No prospective study has been conducted in children. Our objectives were to assess the clinical impact of the length of storage of red blood cell units on clinical outcome in critically ill children. We conducted a prospective, observational study in 30 North American centers, in consecutive patients aged <18 years with a stay ≥48 hours in a pediatric intensive care unit. The primary outcome measure was the incidence of multiple organ dysfunction syndrome after transfusion. The secondary outcomes were 28-day mortality and pediatric intensive care unit length of stay. Odds ratios were adjusted for gender, age, number of organ dysfunctions at admission, total number of transfusions, and total dose of transfusion, using a multiple logistic regression model. Our study showed that for patients receiving blood stored ≥14 days, the adjusted odds ratio for an increased incidence of multiple organ dysfunction syndrome was 1.87 (95% CI 1.04;3.27, p=0.03). There was also a significant difference in the total pediatric intensive care unit length of stay (adjusted median difference +3.7 days, p<0.001) but no significant change in mortality. In critically ill children, transfusion of red blood cell units stored for ≥14 days is independently associated with an increased occurrence of multiple organ dysfunction syndrome and prolonged PICU stay.

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Pokorná, Lenka. "Ošetřovatelské postupy u komplikované peritonitis." Master's thesis, 2019. http://www.nusl.cz/ntk/nusl-404851.

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(v AJ) For my diploma thesis I chose Nursing care for patients with complicated peritonitis as a topic, because care for these patients must be complex and often requires long-term stay at the anesthesiology and resuscitation department. These patients require organ support, undergo repeated surgical revisions, and ultimately, if they overcome this critical period, they learn very often self- care, walking, and sometimes adapt to permanent changes in health. It is a disease where there are often sudden changes in the patient's condition. In the theoretical part I tried to describe the disease leading to the development of peritonitis and complications in the form of septic shock and multiorgan failure. In the National Medical Library, I have searched for a comprehensive review of literature since 2005. I searched for keywords and phrases: Peritonitis, Nursing Care, Sepsis, Multiorgan Failure, Circulatory Support, Artificial Pulmonary Ventilation, Continuous Function Replacement kidney care, laparotomy care, drainage care, intra-abdominal hypertension. I obtained other documents using the central search engine UKAŽ, I drew from licensed databases: Bibliographia medica Čechoslovaca, Ebsco, Medline, Pubmed. For the processing of nursing procedures I used the recommendations of professional societies:...

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Willems, Ariane. "Comparaison entre deux stratégies transfusionnelles en postopératoire de chirurgie cardiaque pédiatrique." Thèse, 2009. http://hdl.handle.net/1866/3637.

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L’anémie est fréquente chez les patients pédiatriques en postopératoire de chirurgie cardiaque. Malgré le nombre important de patients transfusés, le taux d’hémoglobine (Hb) pour lequel les bénéfices surpassent les risques est inconnu chez ces patients. Récemment, Lacroix et al. ont démontré qu’une stratégie transfusionnelle restrictive n’était pas inférieure à une stratégie libérale en ce qui concerne le développement ou la progression du syndrome de défaillance multiviscérale (SDMV) et la mortalité chez les patients de soins intensifs pédiatriques (SIP).Devant le manque d’évidence, une analyse de sous-groupes des patients en postopératoire de chirurgie cardiaque de l’étude Transfusion Requirements in Pediatric Intensive Care (TRIPICU) a été réalisée. L’objectif de cette étude était de déterminer l’impact d’une stratégie transfusionnelle restrictive comparée à une stratégie libérale sur l’acquisition ou l’aggravation du syndrome de défaillance multiviscérale (SDMV) chez les enfants en postopératoire de chirurgie cardiaque. Cette étude n’a pas démontré de différences statistiquement, ni cliniquement significatives du nombre de patients ayant acquis ou aggravés un SDMV, ni des issues secondaires entre les stratégies transfusionnelles restrictive et libérale. L’analyse de sous-groupes permet de générer une hypothèse de recherche et les résultats devraient être confirmés par un essai randomisé contrôlé.
Anemia is frequent in pediatric patients following cardiac surgery. Despite frequent transfusions, the optimal hemoglobin threshold where benefits surpass risks is still unknown for these patients. Recently, Lacroix et al. showed that a restrictive transfusion strategy was not inferior to a liberal strategy concerning the development or progression of multiple organ dysfunction syndrome (MODS) and mortality in pediatric intensive care patients. In the absence of evidence, the aim of this study was to determine the impact of a restrictive versus a liberal transfusion strategy on new or progressive multiple organ dysfunction syndrome (MODS) in children following cardiac surgery. We conducted a subgroup analysis of the postoperative cardiac surgery patients of the Transfusion Requirements in Pediatric Intensive Care Unit (TRIPICU) study. Our study showed no statistically and clinically significant differences in the number of patients who acquired or worsened MODS, nor secondary outcomes between a restrictive and a liberal transfusion strategy. This subgroup analysis generates a research hypothesis that should be confirmed by a randomized controlled trial.

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43

Willems, Ariane. "Comparaison entre deux stratégies transfusionnellles en postopératoire de chirurgie cardiaque pédiatrique." Thèse, 2009. http://hdl.handle.net/1866/3637.

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Анотація:

L’anémie est fréquente chez les patients pédiatriques en postopératoire de chirurgie cardiaque. Malgré le nombre important de patients transfusés, le taux d’hémoglobine (Hb) pour lequel les bénéfices surpassent les risques est inconnu chez ces patients. Récemment, Lacroix et al. ont démontré qu’une stratégie transfusionnelle restrictive n’était pas inférieure à une stratégie libérale en ce qui concerne le développement ou la progression du syndrome de défaillance multiviscérale (SDMV) et la mortalité chez les patients de soins intensifs pédiatriques (SIP).Devant le manque d’évidence, une analyse de sous-groupes des patients en postopératoire de chirurgie cardiaque de l’étude Transfusion Requirements in Pediatric Intensive Care (TRIPICU) a été réalisée. L’objectif de cette étude était de déterminer l’impact d’une stratégie transfusionnelle restrictive comparée à une stratégie libérale sur l’acquisition ou l’aggravation du syndrome de défaillance multiviscérale (SDMV) chez les enfants en postopératoire de chirurgie cardiaque. Cette étude n’a pas démontré de différences statistiquement, ni cliniquement significatives du nombre de patients ayant acquis ou aggravés un SDMV, ni des issues secondaires entre les stratégies transfusionnelles restrictive et libérale. L’analyse de sous-groupes permet de générer une hypothèse de recherche et les résultats devraient être confirmés par un essai randomisé contrôlé.
Anemia is frequent in pediatric patients following cardiac surgery. Despite frequent transfusions, the optimal hemoglobin threshold where benefits surpass risks is still unknown for these patients. Recently, Lacroix et al. showed that a restrictive transfusion strategy was not inferior to a liberal strategy concerning the development or progression of multiple organ dysfunction syndrome (MODS) and mortality in pediatric intensive care patients. In the absence of evidence, the aim of this study was to determine the impact of a restrictive versus a liberal transfusion strategy on new or progressive multiple organ dysfunction syndrome (MODS) in children following cardiac surgery. We conducted a subgroup analysis of the postoperative cardiac surgery patients of the Transfusion Requirements in Pediatric Intensive Care Unit (TRIPICU) study. Our study showed no statistically and clinically significant differences in the number of patients who acquired or worsened MODS, nor secondary outcomes between a restrictive and a liberal transfusion strategy. This subgroup analysis generates a research hypothesis that should be confirmed by a randomized controlled trial.

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