No description available.

No description available.

Typically, simulation project is highly complex process, which relies heavily on the expertise and knowledge of the simulation analyst. It also requires the research of large amounts of systems data. This comprehensive data, together with the specialist skills of the analyst is integral to the success of any simulation project and it would seem obvious that a record of this information is ideally required for future references. However, it appears that, usually, very little or no effort is taken to record and maintain this significant information. This oversight often removes the opportunity for the subsequent use of the model by members of the project team themselves. It also hinders the reuse of simulation models in the development of future models that could use the same data. Hence, proper and complete documentation is seen as an essential requirement to overcome such situations. A simulation study involves, not only developing the model, but also managing the process prior to model construction and subsequent tasks. Documentation in simulation involves, not only recording the model description, but also other exhaustive details embraced with the whole project. Clearly, the project team and model re-users are benefited from such in-depth and effective documentation. Model Representation and Documentation (MRD) is a new concept for documentation in simulation. It addresses the different purposes or needs of different audiences in respect of the simulation project, model reuse, and other interested parties. No structured documentation methodology, either to satisfy this context, or to encompass the complete simulation project has been found in existing literature, or in simulation software. However, it is feasible that a progressive documentation with the model development process would fulfil the needs of different audiences and allows structuring the documentation process. The proposed MRD process is based on task-orientation, which is attributed to the system development methodology in software engineering. It offers the user the ability to manage the documentation process with micro-level of task documents and to capture project details as the project progresses. Subsequently, task documents are accumulated to produce complete documents to fulfil different purposes of documentation. Pre-structured forms of task documents, which are based on typical simulation project procedure and enriched with reusable model elements, not only provide the uniform and consistent structure to capture task details, but also offer a sound foundation for an integrated documentation system. An isolated MRD process, though concurrent with the model development, does not improve the present poor attempt to documentation. The integration of MRD process with model development offers the user the ability to perform both processes simultaneously as a single process while both are benefited directly and mutually through model exchange. The documentation models, which are constructed with reusable generic model elements, and the common database, which stores model details within a standard internal structure, make provision for such model exchange. Hence, an integrated MRD process improves, not only the documentation in simulation, but also model reusability. The study has produced a novel approach for documenting the details of simulation projects in an integrated environment.

In today's world, with ever increasing competition, modelling and simulation proves to be a very helpful tool. Many methodologies exist to help build a simulation model from scratch. In terms of adaptability, most current attempts focus on either the operational side, ie the automated integration of data into a model, or the creation of new software. However, very few attempts are being made to improve the adaptability of shelved models built in existing simulation software. As a result, there is a certain reluctance, in some areas, to use simulation to its full potential. Based on these facts, it is obvious that anything, which makes reuse of simulation models easier, can help improve the use and spread of simulation as a valuable tool to maintain a company's competitiveness. In order to find such a solution, the following issues are looked at in this thesis: The changes to a simulation model that constitute the biggest problem, ways to minimise those changes, and possibilities to simplify the implementation of those changes. Those factors are evaluated, first by investigating current practices of building adaptable simulation models via a literature review, then the most difficult changes to implement in a simulation model, and the most frequent types of simulation software, are identified by means of interviews and questionnaire surveys. Next, parameters describing the adaptability of a simulation model are defined. In a further step, two of the most widely used simulation packages are benchmarked against a variety of tasks, reflecting the changes most frequent to models. The benchmarking study also serves to define and test certain elements regarding their suitability for adaptable models. Based on all those steps, model building guidelines for the creation of adaptable simulation models are developed and then validated by means of interviews and a framed field experiment. The interviews and questionnaire reveal that deleting is the easiest task and modifying the most complicated, while handling devices are the most difficult element to modify. The results also show that simulators (eg Arena) are the most widespread type of simulation software. The benchmarking showed that Arena is overall more adaptable than Simul8, and confirms the findings from the user survey. Also, it shows that sequencing is very helpful for modifying models, while the use of sub-models decrease the adaptability. Finally, the validation proves that the model building guidelines substantially increase the adaptability of models.

This thesis presents a new methodology to accelerate the simulation model development process. Three research strategies were adopted during the research namely; case study, questionnaire survey and literature survey. Investigations done during the research revealed that among the stages within a simulation project life cycle the model development phase is the longest. Results of the case study research and literature review revealed that two major reasons for the lengthiness are the lack of understanding of the system to be simulated between the modeller and the user, and difficulty in programming. Many researchers have tried to accelerate the process mainly by improving the programming efficiency. However it is important to develop a model which represents the actual system to be simulated. Existing approaches to accelerating the simulation model development process do not guarantee that the model developed in a shorter time is the model which represents the actual physical system. Therefore there is a need for a new methodology to develop a model at a shorter time while ensuring that it represents the actual system. A simulation model is a piece of software. Therefore, the new methodology was developed by adopting Rapid Application Development approach of software development which emphasises the active user involvement. There are three components of the proposed methodology; Joint Application Development (JAD) team, a CASE tool to develop the simulation software independent conceptual model of the system, and a translator programme to convert the developed conceptual model into the computer simulation model. The proposed mythology accelerates the model development process not only by improving the effectiveness of the process, i.e. development of the model required by the user once but also the efficiency of the process, i.e. development of the model at a shorter time by automating the model development process.

Chemometrics and Design of Experiments (DOE) are fast becoming integral parts of process analysis and incorporated into the resulting advances in technology. To this end, two major studies were undertaken to explore the existing methods of modelling using both traditional and modern forms of process analytical technology, and to create new methods using the most current developments in the field. The first study involved the use of chemometrics and DOE with low-resolution NMR FID spectra of a series of polymers that were collected over a period of ten months. Accompanying the NMR FID spectra were the associated laboratory reference measurements for a series of quality assurance parameters. This information was used to build an online prediction model for the Xylene Soluble (XS) content of polymer pellets. The installation of the online model was accomplished in numerous stages during which various sample selection methods, including work by Shenk and Westerhaus, were developed and evaluated. The intrinsic nature of the NMR data meant that traditional methods of sample selection could not be employed. The final model used the principal component analysis scores as a means of selecting samples for calibration. DOE was used to determine the best method of pre-processing to be applied to the data prior to partial least squares modelling. The final PLS model was evaluated and the error in prediction for the XS content was found to be 0.672%. The success of this project lead to the installation of this product online at the point of analysis in December 2006. The second study employed chemometrics and DOE with a more traditional method of process analytical technology, the NIR spectral analysis of pharmaceutical tablets. The NIR spectra of over 250 tablets were collected over three production campaigns from 1997 to 1999. Accompanying the NIR spectral data were the chemical and physical tablet parameters, active pharmaceutical ingredient, weight, and tablet thickness. The sample selection techniques developed as part of the polymer study were evaluated. In order to correct for variations due to specular and diffuse scattering effects, extended multiplicative scatter correction was applied to the data. As with the polymer study, DOE was used to determine the best method of data pre-processing prior to the partial least squares modelling. The best method of sample selection for this study was found to be the use of the condition number. The final prediction models for the active pharmaceutical ingredient, weight, and tablet thickness were produced. The final step for this study would be to apply this model online at the point of analysis in the same manner as the polymer study.

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Des progrès remarquables ont été réalisés ces dix dernières années dans le traitement des anévrismes endovasculaires. Les avancées technologiques permettent de traiter un nombre croissant de patients atteints d’anévrismes cérébraux par différentes procédures endovasculaires, en particulier par l’utilisation de coils détachables en platine. L’embolisation vasculaire à l’aide de coils reste néanmoins une procédure médicale complexe qui requiert une planification minutieuse est associée à des compétences techniques avancées pour être réussie. Dans ce contexte, un système de planification informatique qui permet aux radiologistes interventionnels de choisir différents coils et de tester leur comportement dans un environnement spécifique à un patient est particulièrement pertinent. Une telle approche nécessite, outre la modélisation du flux sanguin et la déformation du coil dans un anévrisme, la simulation en (quasi) temps-réel des interactions entre les coils et le flux complexes qui sont présents dans l’anévrisme. Pour parvenir à une simulation précise et rapide, nous introduisons la méthode du calcul extérieur discret (DEC) pour la simulation dynamique. La méthode DEC, initialement introduite en informatique graphique, avait pour objectif de produire des résultats visuellement convaincants mais non physiquement corrects. Nous avons réalisé une analyse détaillée des résultats et une comparaison à l’aide d’un code de calcul de référence a été menée pour comprendre la précision, la stabilité et la complexité algorithmique ainsi que les facteurs qui influencent ces aspects. Nous avons amélioré la stabilité numérique de la méthode DEC par l’utilisation de schémas de retour-arrière avancés et en optimisant la qualité des maillages utilisés dans le calcul. De plus, un compromis optimal entre la précision et le temps de calcul est choisi afin de simuler le flux sanguin de manière très rapide (quasiment temps-réel). En utilisant cette nouvelle approche, nous décrivons également un processus complet pour la simulation propre à chaque patient d’une opération d’embolisation: de la génération de maillages à l’aide d’images médicales jusqu’à au calcul de l’influence réciproque sang-coil. Nous proposons une nouvelle approche en deux phases pour la simulation temps-réel de ces interactions, premièrement en prenant en compte l’influence du flux sanguin sur les premières étapes du déploiement du coil, et deuxièmement en diminuant la vitesse du sang dans l’anévrisme résultant de la densité des coils. Cette approche permet une planification interactive de l’embolisation pour deux étapes clés de la procédure: choix et positionnement du coil suivi d’une estimation du nombre de coils à introduire pour réduire la vélocité du sang dans l’anévrisme. La procédure d’embolisation est simulée en temps-réel dans des anévrismes obtenus à partir de données patients et le status pré et post opératoire est enregistré. Nos résultats de simulations démontrent que l’influence réciproque est essentielle dans le contexte de planification d’embolisation. Enfin, nous proposons une approche préliminaire pour la simulation de l’interaction sang-réseau vasculaire lors de la formation d’un anévrisme. Les résultats de la simulation 2D en utilisant des données patients sont encourageants. / Over the last decade, remarkable progress has been made in the field of endovascular treatment of aneurysms. Technological advances continue to make it possible for a growing number of patients with cerebral aneurysms to be treated with a variety of endovascular strategies, essentially using detachable platinum coils. Yet, coil embolization remains a very complex medical procedure for which careful planning must be combined with advanced technical skills in order to be successful. In this context, a computer-assisted planning system, allowing interventional radiologists to interactively select different coils and test their behavior in a patient-specific environment, could make a difference. This requires to not only model the blood and coil behavior in a patient-specific aneurysm geometry, but also to simulate the interaction between coil(s) and the complex flow occurring within aneurysm in (near) real time. In order to achieve accurate and fast simulation, we introduce the Discrete Exterior Calculus (DEC) method to hemodynamic simulation for the first time. The DEC method, initially introduced in the field of computer graphics, was aimed at visually convincing results, but not physical accuracy. A detailed analysis of the results and comparison with a reference software are performed to understand the accuracy, stability and computational efficiency of the method, as well as the factors affecting these aspects. We improve the numerical stability of the DEC method by using more advanced backtracking schemes, and more importantly by optimizing quality of the mesh used in the computation. Additionally, an optimal trade-off between accuracy and computational time is obtained to simulate the blood flow in (near) real time. Based on this new method for blood flow simulation, we describe a complete process for patient-specific simulation of aneurysm coil embolization, from mesh generation with medical datasets to computation of blood-coil bilateral influence. We propose a new approach to real-time simulation of the twofold interactions, first involving the impact of blood flow on the coil during the initial stages of its deployment, and second concerning the decrease of blood velocity within aneurysm, as a consequence of coil packing. This allows dynamical planning coil embolization for two key steps in the procedure: choice and placement of the first coil, and assessment of the number of coils necessary to reduce the blood velocity within aneurysm. The coil embolization procedure is simulated within patient-specific aneurysms in real time, and pre- and post-operative status is reported. Our simulated results demonstrated that the bilateral influence is essential in the context of planning the coil embolization surgery. Besides, we propose a preliminary framework for the simulation of blood-vessel interaction during the process of aneurysm growth. The results of the two-dimensional simulation using actual patients data sets is encouraging.

Un embryon, initialement composé de cellules identiques, se transforme progressivement en une structure spatialement organisée de tissus distincts aux frontières clairement démarquées. Les interactions cellulaires jouent un rôle clé dans la formation de motifs, et l’effet de communauté est un exemple d’une telle interaction. Une population de cellules dans un embryon présente un effet de communauté quand elle forme une communauté de cellules ayant une identité commune obtenue grâce à l’échange de molécules de signalisation. Cet effet permet aux cellules de la communauté de maintenir un profil d’expression génétique commun.Dans ce travail, nous étudions le comportement de l’effet de communauté dans l’espace et étudions ses rôles dans d’autres processus de formation de motif, en utilisant la modélisation computationnelle:• Une méthode de réduction de modèle est développée pour l’analyse stochastique. Par cette méthode nous avons pu démontrer que le modèle de l’effet de communauté dans Xenopus est influencé par un bruit stochastique.• Nous montrons que l'effet de communauté doit finalement se propager dans l’ensemble de la population de cellules qui réagissent au morphogène.• Deux modèles montrant comment cette expansion peut être contrôlée sont présentés. 1) Si l’effet de communauté est augmenté d’un mécanisme de rétroaction négative, il forme un système qui s’auto-organise et forme une zone d’activation stable et localisée. 2) Quand un circuit simple de répression génétique est associé au circuit produisant l’effet de communauté, un motif d’expression de gène avec une frontière bien démarquée apparaît en réponse à un gradient de morphogène transitoire. / A developing embryo, consisting initially of identical cells, transforms itself into a spatially organized structure made of distinct tissues with clear boundaries. Cell interaction plays a key role in pattern formation, and the community effect is an example of such an interaction. A population of cells in an embryo is said to exhibit a community effect when they form a cell community with a common identity by virtue of exchanging diffusible signalling molecules. This effect helps the cell community to maintain a common gene expression profile over an extended period of time.In this work, we study the behaviour of a community effect in space and investigate its roles in other pattern formation processes, using computational modelling:• A model reduction method is developed for stochastic analysis, and using it we have shown how the model of the community effect in Xenopus is influenced by stochastic noise.• Using a simple spatial community effect model, we show that the community effect spreads across the entire population of cells which respond to the morphogen.• Two models demonstrating how this expansion can be controlled are presented. 1) If the community effect is augmented with a negative feedback mechanism, it forms a reaction-diffusion system which self-organizes and forms a stable, localized area of activation. 2) When a simple cross-repression gene circuitry is combined with a community effect loop, a gene expression pattern with a well-demarcated boundary appears in response to a transient morphogen gradient. The pattern remains stable even after the gradient disappears, which shows that the gene network has the memory of morphogen dynamics.

Cette thèse apporte une solution pour permettre de couplage entre fluide et solide déformable dans le cadre d’applications médicales en temps-réel. Le modèle de couplage concerne le cas d’un film de fluide compris entre deux solides déformables. La première contribution de ce document concerne une méthode de fluide semi-lagrangienne. Nous proposons une modification d’une méthode existante pour pouvoir l’utiliser en tant que modèle de fluide 2.5D. La seconde contribution se concentre sur le modèle de couplage en lui-même où nous avons choisi de prédire le comportement de l’interface fluide-solide pendant le calcul du fluide. La troisième contribution repose sur des applications médicales basées sur cette approche. Elles contribuent dans les domaines de la chirurgie ophtalmologique et reconstruction chirurgicale. / This thesis provides a solution to the coupling of a fluid with a deformable solid in the context of real-time medical applications. This work focuses on the special case of a fluid film embedded within two layers of soft tissues. The first contribution of this document is related to a semi-Lagrangian fluid method. We propose a modification of an existant method to use it as a 2.5D fluid model. The second contribution concerns the coupling model, where the behavior of the fluid-solid interface is predicted during the fluid computation. The third contribution highlights 2 medical applications which rely on this approach, in the fields of eye surgery and reconstructive surgery.