Made available in DSpace on 2017-07-10T17:31:09Z (GMT). No. of bitstreams: 1 Cesar Augusto Lustosa.pdf: 3148509 bytes, checksum: 1509365a24976bafd602471441bde073 (MD5) Previous issue date: 2010-10-14 / The relationship between global and local should be seen in a dialectical perspective, in which neither the whole can be decomposed or divided into parts, neither the sum of its parts reconstitutes the whole, and therefore they are not divided or self organized. In this perspective the theoretical conceptions and experiences focused on planning, isolated regions. The processes of globalization and technological and structural changes have changed the nature and conditions of local development. The locales should be seen as active spaces with culture, history, human and material resources. In this perspective the innovation and institutional stand formats as central elements, both for understanding as for local development policies. To this end we use mainly the references from Sandra Lencioni, Clério Campolina, Eduardo Gonçalves and Ester Limonad among others we search for a thorough interviewing owners and/or managers of industrial units of industrial park "Eduardo Dágios s" employees etc., to information and data about the thematic studied. This dissertation have reviewed: 1) industrial diversity in the State of Paraná, analyzing the formations of industrial parks and because of this a new territorialization of industry in the State and finally a study on the industry in the region of southwestern Paraná; 2) we see the historical formation of industry in Pato Branco until the formation of the industrial park "Eduardo Dágios"; 3) observe the importance that the bairro Planalto has for some people while dwelling place, leisure entertainment and everyday relations; 4) we see the process of industrialization and local development, having as consequence of the increased quality of life promoted by government agencies and industries, by the way the General infrastructure of the bairro Planalto from the creation of the industrial park "Eduardo Dágios". / A relação entre global e o local devem ser vistas em uma perspectiva dialética, na qual nem o todo pode ser fracionado ou dividido em partes, nem a soma das partes reconstitui o todo, pois são auto-organizativos e, portanto, não desmembráveis. Nesta perspectiva, as concepções teóricas e as experiências de planejamento, não estão voltadas para regiões isoladas. O processo de globalização e as mudanças tecnológicas e estruturais mudaram a natureza e as condições do desenvolvimento local. As localidades devem ser vistas como espaços ativos dotados de cultura, história, recursos humanos e materiais diferenciados. Dessa forma, a inovação e os formatos institucionais se sobressaem como elementos centrais, tanto para o entendimento quanto para as políticas de desenvolvimento local. Para tanto, foram utilizados principalmente os referenciais de Sandra Lencioni, Clério Campolina, Eduardo Gonçalves e Ester Limonad entre outros. A partir desses conceitos foi possível ter embasamento suficiente para realizar uma pesquisa minuciosa entrevistando proprietários, administradores e trabalhadores assalariados de unidades industriais do Parque Industrial ―Eduardo Dágios‖, visando obter informações e dados acerca da temática estudada. Nesta dissertação foram analisados: 1) a diversidade industrial no Estado do Paraná e como ocorrem as formações dos parques industriais e como isso influencia a formação de uma nova territorialização da indústria no Estado e também um estudo sobre a indústria na região do Sudoeste do Paraná; 2) verificou-se a formação histórica da indústria em Pato Branco até a formação do Parque Industrial ―Eduardo Dágios‖; 3) observou-se a importância que o bairro Planalto tem para algumas pessoas enquanto lugar de moradia, lazer entretenimento e relações cotidianas; 4) foi verificado o processo de industrialização e o desenvolvimento local, tendo como consequência o aumento da qualidade de vida promovido pelos órgãos públicos e as indústrias, contribuindo significativamente para a melhoria geral de infra-estrutura do bairro Planalto a partir da criação do Parque Industrial ―Eduardo Dágios‖.

Made available in DSpace on 2017-05-12T14:42:41Z (GMT). No. of bitstreams: 1 Cesar Augusto Lustosa.pdf: 3148509 bytes, checksum: 1509365a24976bafd602471441bde073 (MD5) Previous issue date: 2010-10-14 / The relationship between global and local should be seen in a dialectical perspective, in which neither the whole can be decomposed or divided into parts, neither the sum of its parts reconstitutes the whole, and therefore they are not divided or self organized. In this perspective the theoretical conceptions and experiences focused on planning, isolated regions. The processes of globalization and technological and structural changes have changed the nature and conditions of local development. The locales should be seen as active spaces with culture, history, human and material resources. In this perspective the innovation and institutional stand formats as central elements, both for understanding as for local development policies. To this end we use mainly the references from Sandra Lencioni, Clério Campolina, Eduardo Gonçalves and Ester Limonad among others we search for a thorough interviewing owners and/or managers of industrial units of industrial park "Eduardo Dágios s" employees etc., to information and data about the thematic studied. This dissertation have reviewed: 1) industrial diversity in the State of Paraná, analyzing the formations of industrial parks and because of this a new territorialization of industry in the State and finally a study on the industry in the region of southwestern Paraná; 2) we see the historical formation of industry in Pato Branco until the formation of the industrial park "Eduardo Dágios"; 3) observe the importance that the bairro Planalto has for some people while dwelling place, leisure entertainment and everyday relations; 4) we see the process of industrialization and local development, having as consequence of the increased quality of life promoted by government agencies and industries, by the way the General infrastructure of the bairro Planalto from the creation of the industrial park "Eduardo Dágios". / A relação entre global e o local devem ser vistas em uma perspectiva dialética, na qual nem o todo pode ser fracionado ou dividido em partes, nem a soma das partes reconstitui o todo, pois são auto-organizativos e, portanto, não desmembráveis. Nesta perspectiva, as concepções teóricas e as experiências de planejamento, não estão voltadas para regiões isoladas. O processo de globalização e as mudanças tecnológicas e estruturais mudaram a natureza e as condições do desenvolvimento local. As localidades devem ser vistas como espaços ativos dotados de cultura, história, recursos humanos e materiais diferenciados. Dessa forma, a inovação e os formatos institucionais se sobressaem como elementos centrais, tanto para o entendimento quanto para as políticas de desenvolvimento local. Para tanto, foram utilizados principalmente os referenciais de Sandra Lencioni, Clério Campolina, Eduardo Gonçalves e Ester Limonad entre outros. A partir desses conceitos foi possível ter embasamento suficiente para realizar uma pesquisa minuciosa entrevistando proprietários, administradores e trabalhadores assalariados de unidades industriais do Parque Industrial ―Eduardo Dágios‖, visando obter informações e dados acerca da temática estudada. Nesta dissertação foram analisados: 1) a diversidade industrial no Estado do Paraná e como ocorrem as formações dos parques industriais e como isso influencia a formação de uma nova territorialização da indústria no Estado e também um estudo sobre a indústria na região do Sudoeste do Paraná; 2) verificou-se a formação histórica da indústria em Pato Branco até a formação do Parque Industrial ―Eduardo Dágios‖; 3) observou-se a importância que o bairro Planalto tem para algumas pessoas enquanto lugar de moradia, lazer entretenimento e relações cotidianas; 4) foi verificado o processo de industrialização e o desenvolvimento local, tendo como consequência o aumento da qualidade de vida promovido pelos órgãos públicos e as indústrias, contribuindo significativamente para a melhoria geral de infra-estrutura do bairro Planalto a partir da criação do Parque Industrial ―Eduardo Dágios‖.

In this thesis, we study three supply chain planning problems. The first two problems fall in the tactical planning level, while the third one falls in the strategic/tactical level. We present a direct application for the first two planning problems in the wind turbines industry. For the third problem, we show how it can be applied to supply chains in the food industry. Many countries and localities have the explicitly stated goal of increasing the fraction of their electrical power that is generated by wind turbines. This has led to a rapid growth in the manufacturing and installation of wind turbines. The globally installed capacity for the manufacturing of different components of the wind turbine is nearly fully utilized. Because of the large penalties for missing delivery deadlines for wind turbines, the effective planning of its supply chain has a significant impact on the profitability of the turbine manufacturers. Motivated by the planning challenges faced by one of the world’s largest manufacturers of wind turbines, we present a comprehensive tactical supply chain planning model for manufacturing of wind turbines in the first part of this thesis. The model is multi-period, multi-echelon, and multi-commodity. Furthermore, the model explicitly incorporates backorder penalties with a general cost structure, i.e., the cost structure does not have to be linear in function of the backorder delay. To the best of our knowledge, modeling-based supply chain planning has not been applied to wind turbines, nor has a model with all the above mentioned features been described in the literature. Based on real-world data, we present numerical results that show the significant impact of the capability to model backorder penalties with general cost structures on the overall cost of supply chains for wind turbines. With today’s rapidly changing global market place, it is essential to model uncertainty in supply chain planning. In the second part of this thesis, we develop a two-stage stochastic programming model for the comprehensive tactical planning of supply chains under supply uncertainty. In the first stage, procurement decisions are made while in the second stage, production, inventory, and delivery decisions are made. The considered supply uncertainty combines supplier random yields and stochastic lead times, and is thus the most general form of such uncertainty to date. We apply our model to the same wind turbines supply chain. We illustrate theoretical and numerical results that show the impact of supplier uncertainty/unreliability on the optimal procurement decisions. We also quantify the value of modeling uncertainty versus deterministic planning. Supplier selection with quantity discounts has been an active research problem in the operations research community. In this the last part of this thesis, we focus on a new quantity discounts scheme offered by suppliers in some industries. Suppliers are selected for a strategic planning period (e.g., 5 years). Fixed costs associated with suppliers’ selection are paid. Orders are placed monthly from any of the chosen suppliers, but the quantity discounts are based on the aggregated annual order quantities. We incorporate all this in a multi-period multi-product multi-echelon supply chain planning problem and develop a mixed integer programming (MIP) model for it. Leading commercial MIP solvers take 40 minutes on average to get any feasible solution for realistic instances of our model. With the aim of getting high-quality feasible solutions quickly, we develop an algorithm that constructs a good initial solution and three other iterative algorithms that improve this initial solution and are capable of getting very fast high quality primal solutions. Two of the latter three algorithms are based on MIP-based local search and the third algorithm incorporates a variable neighborhood Descent (VND) combining the first two. We present numerical results for a set of instances based on a real-world supply chain in the food industry and show the efficiency of our customized algorithms. The leading commercial solver CPLEX finds only a very few feasible solutions that have lower total costs than our initial solution within a three hours run time limit. All our iterative algorithms well outperform CPLEX. The VND algorithm has the best average performance. Its average relative gap to the best known feasible solution is within 1% in less than 40 minutes of computing time.

Dans ce travail, nous définissons des objets composés de disques complexes marqués reliés entre eux par des segments de droite munis d’une longueur. Nous construisons deux séries d’espaces de module de ces objets appelés clus- ters, une qui sera dite non symétrique, la version ⊗, et l’autre qui est dite symétrique, la version •. Cette construction permet des choix de perturba- tions pour deux versions correspondantes des trajectoires de Floer introduites par Cornea et Lalonde ([CL]). Ces choix devraient fournir une nouvelle option pour la description géométrique des structures A∞ et L∞ obstruées étudiées par Fukaya, Oh, Ohta et Ono ([FOOO2],[FOOO]) et Cho ([Cho]). Dans le cas où L ⊂ (M, ω) est une sous-variété lagrangienne Pin± mono- tone avec nombre de Maslov ≥ 2, nous définissons une structure d’algèbre A∞ sur les points critiques d’une fonction de Morse générique sur L. Cette struc- ture est présentée comme une extension du complexe des perles de Oh ([Oh]) muni de son produit quantique, plus récemment étudié par Biran et Cornea ([BC]). Plus généralement, nous décrivons une version géométrique d’une catégorie de Fukaya avec seul objet L qui se veut alternative à la description (relative) hamiltonienne de Seidel ([Sei]). Nous vérifions la fonctorialité de notre construction en définissant des espaces de module de clusters occultés qui servent d’espaces sources pour des morphismes de comparaison. / We define objects made of marked complex disks connected by metric line seg- ments and construct two sequences of moduli spaces of these objects, referred as the ⊗ version (nonsymmetric) and the • version (symmetric). This allows choices of coherent perturbations over the corresponding versions of the Floer trajectories proposed by Cornea and Lalonde ([CL]). These perturbations are intended to lead to an alternative geometric description of the (obstructed) A∞ and L∞ structures studied by Fukaya, Oh, Ohta and Ono ([FOOO2],[FOOO]) and Cho ([Cho]). Given a Pin± monotone lagrangian submanifold L ⊂ (M, ω) with mini- mal Maslov number ≥ 2, we define an A∞ -algebra structure from the critical points of a generic Morse function on L. We express this structure as a cochain complex extending the pearl complex introduced by Oh ([Oh]) and further ex- plicited by Biran and Cornea ([BC]), equipped with its quantum product. This could also be seen as an alternative geometric description of a Fukaya cate- gory of (M, ω) with L as its only object, a hamiltonian relative version appear- ing in [Sei]. Using spaces of quilted clusters, we verify, using more general quilted cluster spaces, that this defines a functor from a homotopy category of Pin± monotone lagrangian submanifolds hL mono,± (M, ω) to the homotopy category of cochain complexes hK(Λ-mod) where Λ is an appropriate Novikov ring.

L’approche psycholinguistique suggère que la rétention à court terme verbale et le langage dépendent de mécanismes communs. Elle prédit que les caractéristiques linguistiques des items verbaux (e.g. phonologiques, lexicales, sémantiques) influencent le rappel immédiat (1) et que la contribution des niveaux de représentations linguistiques dépend du contexte de rappel, certaines conditions expérimentales (e.g. format des stimuli) favorisant l’utilisation de codes spécifiques (2). Ces prédictions sont évaluées par le biais de deux études empiriques réalisées auprès d’une patiente cérébrolésée qui présente une atteinte du traitement phonologique (I.R.) et de participants contrôles. Une première étude (Article 1) teste l’impact des modes de présentation et de rappel sur les effets de similarité phonologique et de catégorie sémantique de listes de mots. Une seconde étude (Article 2) évalue la contribution du code orthographique en mémoire à court terme (MCT) verbale en testant l’effet de la densité du voisinage orthographique des mots sur le rappel sériel immédiat de mots présentés visuellement. Compte tenu du rôle déterminant du code phonologique en MCT et du type d’atteinte de I.R., des effets linguistiques distincts étaient attendus chez elle et chez les contrôles. Selon le contexte de rappel, des effets sémantiques (Article 1) et orthographiques (Article 2) plus importants étaient prédits chez I.R. et des effets phonologiques plus marqués étaient attendus chez les participants contrôles. Chez I.R., le rappel est influencé par les caractéristiques sémantiques et orthographiques des mots, mais peu par leurs caractéristiques phonologiques et le contexte de rappel module l’utilisation de différents niveaux de représentations linguistiques. Chez les contrôles, une contribution relativement plus stable des représentations phonologiques est observée. Les données appuient une approche psycholinguistique qui postule que des mécanismes communs régissent la rétention à court terme verbale et le langage. Les implications théoriques et cliniques des résultats sont discutées en regard de modèles psycholinguistiques actuels. / The psycholinguistic view of verbal short-term retention suggests that verbal short-term retention and language processing rely on common mechanisms. It predicts that all linguistic characteristics of verbal items (e.g. phonological, lexical, semantic) influence their immediate recall (1). It also predicts that the relative contribution of the different linguistic representational levels is a function of the recall context (2). In this view, some experimental conditions (e.g. modes of presentation of stimuli) are thought to promote the use of specific coding. Two studies assess these predictions in a brain-damaged patient (I.R.) who shows a phonological deficit as well as in control participants. In a first article, the impact of presentation and recall modes on phonological and semantic similarity effects of words is tested. In a second article, the contribution of orthographic coding in verbal short-term memory (STM) is assessed by testing the effect of orthographic Neighborhood (N) density of words on immediate serial recall (ISR) of written words. Due to her phonological deficit and because phonological representations play a predominant role in STM, distinct linguistic effects were expected in I.R. and in controls. Overall, (and) depending on the recall context, larger semantic and orthographic effects were predicted in I.R. and larger phonological effects were predicted in controls. In I.R., the data indicate that recall is influenced by semantic and orthographic characteristics of items but less by their phonological properties. The results also indicate that the impact of representations depends of recall conditions. In controls, a different pattern of results is obtained, suggesting an overall predominant contribution of phonological representations. Results support the psycholinguistic view of verbal short-term retention and are discussed in regard to current interactive activation psycholinguistic models of verbal STM and language processing.

L’implantation répandue de nouveaux quartiers résidentiels sur le territoire de la périphérie urbaine est en partie responsable de la baisse du couvert végétal et de l’augmentation des surfaces imperméables à grande échelle. Les villes sont maintenant aux prises avec une augmentation constante de la production de ruissellement qu'elles doivent gérer au moyen d’un vaste réseau d’égouts et de canalisations. Des données sur les impacts de ces modèles de quartier résidentiel nous révèlent que cette forme d’habitat provoque la dégradation des milieux naturels et aquatiques. La présente étude vise à mettre à l’épreuve la stratégie d’aménagement de l’Open space design en comparant l’effet de trois situations d’aménagement d’ensembles résidentiels sur le coefficient de ruissellement pondéré (Cp). Les trois situations étudiées sont 1 : le développement actuel tel que conçu par le promoteur, 2 : un scénario de quartier visant la préservation des cours d’eau existants ainsi qu’une réduction des lots et des surfaces imperméables et 3 : un quartier avec des types d’habitation plus denses. Les coefficients pondérés obtenus sont respectivement de 0,50 pour le quartier actuel, de 0,40 pour le scénario 1 et de 0,34 pour le scénario 2. Au terme de cet exercice, il apparaît, d’une part, que la densification du bâti, la nature des surfaces et l’organisation spatiale peuvent concourir à diminuer la production de ruissellement d’un quartier. Cette étude permet de situer l’importance de la gestion du ruissellement dans la planification et l’aménagement du territoire. / The widespread introduction of new residential developments in the urban periphery is partly responsible for declining vegetation cover and a large scale increase in impervious surfaces. Cities are now grappling with a constant increase in runoff, which they have to manage through a vast network of sewers and drains. Data on the impacts of current residential models reveal that this form of development causes the degradation of natural and aquatic environments. The present study aims to test Open space design strategy by comparing the effect of three development situations on the weighted runoff coefficient (Cw). The three situations are 1: the actual development as conceived by the project’s promoter; 2: development aimed at preserving existing streams, reducing lot sizes and impervious surfaces; and 3: a higher-density cluster development plan. The weighted coefficients obtained are 0.50 for scenario 1, 0.40 for scenario 2 and 0.34 for scenario 3. As a result, it appears that the density of the structures, the nature of the surfaces and the spatial organization can all contribute to reducing the runoff in a given area. This study underlines the importance of runoff management in planning and land use.

Cette thèse porte sur les problèmes de tournées de véhicules avec fenêtres de temps où un gain est associé à chaque client et où l'objectif est de maximiser la somme des gains recueillis moins les coûts de transport. De plus, un même véhicule peut effectuer plusieurs tournées durant l'horizon de planification. Ce problème a été relativement peu étudié en dépit de son importance en pratique. Par exemple, dans le domaine de la livraison de denrées périssables, plusieurs tournées de courte durée doivent être combinées afin de former des journées complètes de travail. Nous croyons que ce type de problème aura une importance de plus en plus grande dans le futur avec l'avènement du commerce électronique, comme les épiceries électroniques, où les clients peuvent commander des produits par internet pour la livraison à domicile. Dans le premier chapitre de cette thèse, nous présentons d'abord une revue de la littérature consacrée aux problèmes de tournées de véhicules avec gains ainsi qu'aux problèmes permettant une réutilisation des véhicules. Nous présentons les méthodologies générales adoptées pour les résoudre, soit les méthodes exactes, les méthodes heuristiques et les méta-heuristiques. Nous discutons enfin des problèmes de tournées dynamiques où certaines données sur le problème ne sont pas connues à l'avance. Dans le second chapitre, nous décrivons un algorithme exact pour résoudre un problème de tournées avec fenêtres de temps et réutilisation de véhicules où l'objectif premier est de maximiser le nombre de clients desservis. Pour ce faire, le problème est modélisé comme un problème de tournées avec gains. L'algorithme exact est basé sur une méthode de génération de colonnes couplée avec un algorithme de plus court chemin élémentaire avec contraintes de ressources. Pour résoudre des instances de taille réaliste dans des temps de calcul raisonnables, une approche de résolution de nature heuristique est requise. Le troisième chapitre propose donc une méthode de recherche adaptative à grand voisinage qui exploite les différents niveaux hiérarchiques du problème (soit les journées complètes de travail des véhicules, les routes qui composent ces journées et les clients qui composent les routes). Dans le quatrième chapitre, qui traite du cas dynamique, une stratégie d'acceptation et de refus des nouvelles requêtes de service est proposée, basée sur une anticipation des requêtes à venir. L'approche repose sur la génération de scénarios pour différentes réalisations possibles des requêtes futures. Le coût d'opportunité de servir une nouvelle requête est basé sur une évaluation des scénarios avec et sans cette nouvelle requête. Enfin, le dernier chapitre résume les contributions de cette thèse et propose quelques avenues de recherche future. / This thesis studies vehicle routing problems with time windows, where a gain is associated with each customer and where the objective is to maximize the total gain collected minus the routing costs. Furthermore. the same vehicle might be assigned to different routes during the planning horizon. This problem has received little attention in the literature in spite of its importance in practice. For example, in the home delivery of perishable goods (like food), routes of short duration must be combined to form complete workdays. We believe that this type of problem will become increasingly important in the future with the advent of electronic services, like e-groceries, where customers can order goods through the Internet and get these goods delivered at home. In the first chapter of this thesis, we present a review of vehicle routing problems with gains, as well as vehicle routing problems with multiple use of vehicles. We discuss the general classes of problem-solving approaches for these problems, namely, exact methods, heuristics and metaheuristics. We also introduce dynamic vehicle routing problems, where new information is revealed as the routes are executed. In the second chapter, we describe an exact algorithm for a vehicle routing problem with time windows and multiple use of vehicles, where the first objective is to maximize the number of served customers. To this end, the problem is modeled as a vehicle routing problem with gains. The exact algorithm is based on column generation, coupled with an elementary shortest path algorithm with resource constraints. To solve realistic instances in reasonable computation times, a heuristic approach is required. The third chapter proposes an adaptative large neighborhood search where the various hierarchical levels of the problem are exploited (i.e., complete vehicle workdays, routes within workdays and customers within routes). The fourth chapter deals with the dynamic case. In this chapter, a strategy for accepting or rejecting new customer requests is proposed. This strategy is based on the generation of multiple scenarios for different realizations of the requests in the future. An opportunity cost for serving a new request is then computed, based on an evaluation of the scenarios with and without the new request. Finally, the last chapter summarizes the contributions of this thesis and proposes future research avenues.

The astronomical increase in the number of wireless devices such as smart phones in 21th century has revolutionized the way people communicate with one another and share information. The new wireless technologies have also enabled researchers to collect real data about how people move and meet one another in different social settings. Understanding human mobility has many applications in different areas such as traffic planning in cities and public health studies of epidemic diseases. In this thesis, we study the fundamental properties of human contact graphs in order to characterize how people meet one another in different social environments. Understanding human contact patterns in return allows us to propose a cost-effective routing algorithm for spreading information in Delay Tolerant Networks. Furthermore, we propose several contact predictors to predict the unobserved parts of contact graphs when only partial observations are available. Our results show that we are able to infer hidden contacts of real contact traces by exploiting the underlying properties of contact graphs. In the last few years, we have also witnessed an explosion in the number of people who use social media to share information with their friends. In the last part of this thesis, we study the running times of several information spreading algorithms in social networks in order to find the fastest strategy. Fast information spreading has an obvious application in advertising a product to a large number of people in a short amount of time. We prove that a fast information spreading algorithm should efficiently identify communication bottlenecks in order to speed up the running time. Finally, we show that sparsifying large social graphs by exploiting the edge-betweenness centrality measure can also speed up the information spreading rate. / Graduate

Σκοπός της παρούσας διδακτορικής διατριβής είναι η ανάπτυξη ενός ολοκληρωμένου συστήματος υποστήριξης της διάγνωσης (Decision Support System - DSS) με χρήση μεθόδων εξόρυξης δεδομένων για την ταξινόμηση επιχρισμάτων βιοψίας με λεπτή βελόνα (Fine Needle Aspiration - FNA). Δύο κατηγορίες επιλέχθηκαν για τα δείγματα FNA: καλοήθεια και κακοήθεια. Το σύστημα αυτό αποτελείται από τις ακόλουθες βαθμίδες: 1) συλλογής δεδομένων, 2) επιλογής δεδομένων, 3) εύρεσης κατάλληλων χαρακτηριστικών, 4) εφαρμογής ταξινόμησης με χρήση μεθόδων εξόρυξης δεδομένων. Επίσης, βασικός στόχος της παρούσας διδακτορικής διατριβής ήταν η βελτίωση της ορθής ταξινόμησης των ύποπτων επιχρισμάτων (suspicious), για τα οποία είναι γνωστή η αδυναμία της μεθόδου FNA να τα ταξινομήσει. Το σύστημα εκπαιδεύτηκε και ελέγχθηκε σε σχέση με το δείγμα για το οποίο είχαμε ιστολογικές επιβεβαιώσεις (ground truth). Για περιπτώσεις οι οποίες χαρακτηρίστηκαν ως μη κακοήθεις από την FNA, και για τις οποίες δεν είχαμε ιστολογικές επιβεβαιώσεις, το δείγμα προέκυψε από την συνεκτίμηση και άλλων κλινικών, εργαστηριακών και απεικονιστικών εξετάσεων. Στα πλαίσια της παρούσας διδακτορικής διατριβής συλλέχθηκαν εξετάσεις FNA θυρεοειδούς από το Εργαστήριο Παθολογοανατομίας του Α’ Τμήματος Παθολογίας της Ιατρικής Σχολής του Πανεπιστημίου Αθηνών. Δεδομένου ότι το εν λόγω εργαστήριο λειτουργεί και σαν κέντρο αναφοράς, σημαντικός αριθμός των δειγμάτων εστάλησαν εκεί και από άλλα Εργαστήρια Παθολογοανατομίας για επανέλεγχο. Το αρχειακό υλικό ήταν πολύ καλά ταξινομημένο σε χρονολογική σειρά αλλά ήταν σε έντυπη μορφή. Αρχικά πραγματοποιήθηκε η ανάλυση απαιτήσεων για τη δομή και το σχεδιασμό της βάσης δεδομένων. Με βάση τα στοιχεία από την τεκμηριωμένη διάγνωση σχεδιάστηκε και αναπτύχθηκε προηγμένο σύστημα για την κωδικοποίηση και αρχικοποίηση των δεδομένων. Με τη βοήθεια του σχεδιασμού και ανάλυσης απαιτήσεων αναπτύχθηκε και υλοποιήθηκε η βάση δεδομένων στην οποία αποθηκεύτηκαν τα δεδομένα προς επεξεργασία. Παράλληλα, με το σχεδιασμό της βάσης έγινε και η προεργασία για το σχεδιασμό και την ανάλυση απαιτήσεων του γραφικού περιβάλλοντος εισαγωγής στοιχείων. Λαμβάνοντας υπόψη ότι το σύστημα θα μπορούσε να χρησιμοποιηθεί και πέρα από τα πλαίσια της παρούσας διδακτορικής διατριβής λήφθηκε μέριμνα ώστε να παρέχεται ένα φιλικό και ευέλικτο προς το χρήστη περιβάλλον. Σύμφωνα με τη μεθοδολογία προσέγγισης η οποία ακολουθήθηκε προηγήθηκε στατιστική ανάλυση των 9.102 συλλεχθέντων δειγμάτων FNA ως προς τα κυτταρολογικά χαρακτηριστικά τους και τις διαγνώσεις. Οι κυτταρολογικές διαγνώσεις των συγκεκριμένων δειγμάτων συσχετίστηκαν με τις ιστολογικές διαγνώσεις, στοχεύοντας στον υπολογισμό της πιθανής επίδρασης και συμβολής κάθε κυτταρολογικού χαρακτηριστικού σε μια ορθή ή ψευδή κυτταρολογική διάγνωση, έτσι ώστε να προσδιοριστούν οι πιθανές πηγές λανθασμένης διάγνωσης. Τα δείγματα τα οποία περιείχαν μόνο αίμα ή πολύ λίγα θυλακειώδη κύτταρα χωρίς κολλοειδές θεωρήθηκαν ανεπαρκή για τη διάγνωση. Οι βιοψίες εκτελέσθηκαν είτε στο Α’ τμήμα του Πανεπιστημίου Αθηνών (οι περισσότερες από τις περιπτώσεις με ψηλαφητούς όζους) είτε αλλού (κυρίως κάτω από την καθοδήγηση του κέντρου αναφοράς). Τα δείγματα επιστρωμένα σε πλακάκια, στάλθηκαν στο κέντρο αναφοράς από διάφορα νοσοκομεία, με διαφορετικά πρωτόκολλα σχετικά με τα κριτήρια εκτέλεσης βιοψίας FNA σε θυρεοειδή. Μετεγχειρητικές ιστολογικές επαληθεύσεις ήταν διαθέσιμες για 266 ασθενείς (κακοήθειες και μη). Το χαμηλό ποσοστό ιστολογικών επαληθεύσεων οφείλεται στην ετερογενή προέλευση των ασθενών και στην έλλειψη ολοκληρωμένης παρακολούθησης και επανελέγχου των ασθενών. Για την αξιολόγηση των δεδομένων χρησιμοποιήθηκαν περιγραφικά στατιστικά μεγέθη όπως, μέση τιμή, τυπική απόκλιση, ποσοστά, μέγιστο και ελάχιστο. Έγιναν επίσης και χ2 δοκιμές επιπέδου σημαντικότητας διαφόρων παραμέτρων για να ελεγχθεί η πιθανή συσχέτιση ή η ανεξαρτησία. Για τη συσχέτιση των κυτταρολογικών και των ιστολογικών διαγνώσεων και την αξιολόγηση των εργαστηριακών ευρημάτων, πέραν των περιγραφικών στατιστικών μεγεθών χρησιμοποιήθηκαν και υπολογισμοί της ευαισθησίας, της ειδικότητας, της συνολικής ακρίβειας, της αρνητικής και θετικής αξίας πρόβλεψης (negative and positive predictive value). Προκειμένου να καθοριστεί εάν μια κατηγορία ασθενειών συσχετίζεται ή όχι με συγκεκριμένες κυτταρολογικές παραμέτρους εφαρμόστηκε μέθοδος ελέγχου στατιστικής σημαντικότητας σε επίπεδο 5% (p < 0,05). Η διαδικασία ακολουθήθηκε για κάθε κατηγορία ασθενειών ή συνδυασμό τους και για κάθε παράμετρο των κυτταρολογικών και αρχιτεκτονικών στοιχείων της κυτταρολογικής διάγνωσης. Τα αποτελέσματα της στατιστικής ανάλυσης επέτρεψαν το διαχωρισμό των δεδομένων σε καλοήθη, κακοήθη, νεοπλασματικά, ύποπτα για κακοήθεια και οριακά με χαρακτηριστικά γνωρίσματα μεταξύ ενός καλοήθους και ενός νεοπλασματικού. Στην συνέχεια αναπτύχθηκε σύστημα υποστήριξης της διάγνωσης χρησιμοποιώντας εξειδικευμένες μεθόδους εξόρυξης δεδομένων. Το σύστημα αποτελείται από τέσσερις βαθμίδες. Η πρώτη βαθμίδα αυτού του συστήματος είναι το περιβάλλον Συλλογής Δεδομένων στην οποία τα δεδομένα αποθηκεύονται στη βάση δεδομένων. Η Δεύτερη Βαθμίδα αυτού του συστήματος αφορά στην Επιλογή Δεδομένων. Σύμφωνα με την καταγραφή των απαιτήσεων, την εισαγωγή και τη ψηφιοποίηση των στοιχείων, δημιουργήθηκαν 111 χαρακτηριστικά για κάθε ασθενή (record). Τα περισσότερα χαρακτηριστικά είχαν τιμές δυαδικού τύπου, αποτυπώνοντας την ύπαρξη ή μη του κάθε χαρακτηριστικού, ενώ κάποιες άλλες είχαν τιμές τύπων αριθμών ή αλφαριθμητικών χαρακτήρων. Από τα 111 χαρακτηριστικά επιλέχθηκαν 60 χαρακτηριστικά τα οποία περιγράφουν τη δομή των επιχρισμάτων ενώ δημιουργήθηκαν άλλα 7 χαρακτηριστικά τα οποία αφορούσαν στην ομαδοποίηση άλλων χαρακτηριστικών. Η Τρίτη Βαθμίδα του συστήματος αφορά στην εύρεση των Κατάλληλων Χαρακτηριστικών. Λόγω του αρχικά υψηλού αριθμού χαρακτηριστικών παραμέτρων (67 ανά περίπτωση), ήταν απαραίτητο να εξαλειφθούν οι χαρακτηριστικές παράμετροι που συσχετίζονταν γραμμικά ή δεν είχαν καμία διαγνωστική πληροφορία. H μέθοδος επιλογής χαρακτηριστικών εφαρμόστηκε πριν από την ταξινόμηση, με γνώμονα την ανεύρεση ενός υποσυνόλου των χαρακτηριστικών παραμέτρων που βελτιστοποιούν σε ακρίβεια τη διαδικασία ταξινόμησης. Εφαρμόστηκε η τεχνική επιπλέουσας πρόσθιας ακολουθιακά μεταβαλλόμενης επιλογής (SFFS). Ο αριθμός των δειγμάτων που χρησιμοποιήθηκαν είναι 2.036 (1.886 καλοήθειες και 150 κακοήθειες). Εξ αυτών, όλες οι κακοήθειες είναι ιστολογικά επιβεβαιωμένες. Επίσης, 140 καλοήθειες είναι ιστολογικά επιβεβαιωμένες με επάρκεια υλικού. Οι υπόλοιπες 1.726 καλοήθειες είναι επιβεβαιωμένες με συνεκτίμηση κλινικών, εργαστηριακών και απεικονιστικών ιατρικών εξετάσεων (υπέρηχοι κ.λπ.). Από τα 2.036 δείγματα, το 25% χρησιμοποιήθηκε για την επιλογή χαρακτηριστικών παραμέτρων, δηλαδή 37 περιπτώσεις κακοήθειας (Malignant) και 472 περιπτώσεις καλοήθειας (Non Malignant). Από την εφαρμογή της τεχνικής (SFFS) επιλέχθηκαν τελικά 12 χαρακτηριστικά ως βέλτιστα για την ταξινόμηση των δεδομένων FNA σε καλοήθη και κακοήθη. Η Τέταρτη βαθμίδα επεξεργασίας είναι η Εφαρμογής Ταξινόμησης με χρήση Μεθόδων Εξόρυξης Δεδομένων ή Ταξινομητής. Για το σκοπό αυτό, επιλέχθηκε να εφαρμοστεί μια πληθώρα αξιόπιστων, καλά επιβεβαιωμένων και σύγχρονων μεθόδων εξόρυξης δεδομένων. Το σύστημα εκπαιδεύτηκε και ελέγχθηκε σε σχέση με το δείγμα για το οποίο είχαμε ιστολογικές επιβεβαιώσεις (ground truth). Η ανεξάρτητη εφαρμογή τεσσάρων αξιόπιστων μεθόδων, Δέντρων Αποφάσεων (Decision Trees), Τεχνιτών Νευρωνικών Δικτύων (Artificial Neural Network), Μηχανών Στήριξης Διανυσμάτων (Support Vector Machine), και Κ - κοντινότερου γείτονα (k-NN), έδωσε αποτελέσματα συγκρίσιμα με αυτά της FNA μεθόδου. Περαιτέρω βελτίωση των αποτελεσμάτων επιτεύχθηκε με την εφαρμογή της μεθόδου πλειοψηφικού κανόνα (Majority Vote - CMV) συνδυάζοντας τα αποτελέσματα από την εφαρμογή των τριών καλύτερων αλγορίθμων, ήτοι των Νευρωνικών Δικτύων, Μηχανών Στήριξης Διανυσμάτων και Κ - κοντινότερου γείτονα. Η τροποποιημένη μέθοδος τεχνητών αυτοάνοσων συστημάτων (Artificial Immune Systems – AIS) χρησιμοποιήθηκε για πρώτη φορά στην ταξινόμηση και παρουσίασε ιδιαίτερα βελτιωμένα αποτελέσματα στην ταξινόμηση των επιχρισμάτων τα οποία χαρακτηρίζονται ύποπτα (suspicious) από τους ειδικούς και αποτελούν το αδύναμο σημείο της μεθόδου FNA. Αυτές οι περιπτώσεις υπόνοιας αποτελούν ένα πολύ δύσκολο κομμάτι για τη διάκριση μεταξύ των καλοηθειών και των κακοηθειών, ακόμα και για τους πλέον ειδικούς. Επειδή όλα τα περιστατικά που χαρακτηρίζονται από την βιοψία FNA ως υπόνοιες αντιμετωπίζονται κλινικά σαν κακοήθειες, η εφαρμογή των αλγοριθμικών μεθόδων βελτιώνει αισθητά τη διαχείριση αυτών των περιπτώσεων μειώνοντας τον αριθμό των άσκοπων χειρουργικών επεμβάσεων θυρεοειδεκτομών. / The Aim of present thesis is the development of an integrated system for supporting diagnosis (Decision Support System - DSS) using for categorizing FNA biopsy smears. Two categories were selected for the FNA smears: malignant and nonmalignant. The system is constituted by the following stages of 1) data collection, 2) data selection 3) choice of suitable clinical and cytological features, 4) application of data mining method for the categorization of FNA biopsy smears. Furthermore a fundamental objective of the doctoral thesis was the improvement of suspect smears (suspicious) categorization, for the latter FNA Biopsy has a known restriction. The system had been trained and checked in relation to the sample that histologic evaluation existed (ground truth). For smears that characterized as nonmalignant by FNA and histological data we’re not available, complementary clinical, laboratory and imaging evaluations took into account in order to create the sample. Τhe smears that were available in this thesis, were collected from FNA biopsies in Pathologoanatomy Laboratory, A’ Pathology Department, Medical School of Athens University. Given that the above referred laboratory is a reference center, an important number of FNA smears were sent to it from other laboratories for cross check. The examination files were sorted in chronological order, but there were in paper forms. The requirements for the formation and the design of database system were collected. Based on the material of the diagnosis an improved system was designed and developed for data initialization and coding. The database was developed based on the design and analysis of requirements; in this database data were stored for further investigation. Analysis of the graphical user interface design was performed in parallel to the database design. Taking into account that the system might be used after the completion of thesis, the graphical user interface was designed in order to be user friendly and flexible environment. According to the methodological approach that was followed, the various cytological characteristic of 9102 FNA smears aspired among 2000-2004 was analyzed statistically. The cytological reports cross correlated with histological diagnoses, aiming to calculate the effect or contribution of each cytological characteristic to a false or true cytological diagnosis and to find the possible sources of erroneous diagnosis. The smears that have blood or a few follicular cells without colloid were characterized as insufficient for further diagnosis. The aspiration was performed either in Α’ department of Athens University (most of the cases with palpable nodules) or elsewhere (mainly under guidance of the reference center). The acquired smears being send to the reference center from various hospitals with different protocols concerning criteria to perform a thyroid FNA. Histological reports were available for 266 patients. The small number of histological verifications was due to the heterogeneity and the lack of patients files. For evaluating of data, descriptive statistic values were used like mean, standard deviation, percentage, maximum and minimum. In addition to that χ2 tests of significance were performed in order to check possible correlation or independence. For correlating cytological and histological diagnosis and evaluating laboratory findings, apart from the descriptive statistic parameters also calculated sensitivity, specificity, total accuracy, negative predictive value and positive predictive value. Method of statistical significance in the level of 5% (p < 0,05) was applied in order to specify if a disease was correlated to a cytological parameter. Those checks were performed for each disease category in correlation to any cytological parameter. Statistical analysis divided the smears into nonmalignant, malignant, neoplasms, suspicious for malignancy and borderline. A diagnosis support system was implemented using data mining methods. The system is consisted of four stages. The First stage of the system is the Data Collection environment, which stores the data to the database. The Second stage of this system concerns the Selection of Data. User requirements concluded that 111 characteristics are needed to describe each patient (record). Most of them have binary values, presenting existence and not existence, other have alphanumeric and number values. Among them 60 were selected and 7 more are produced from grouping other characteristics. The final analysis reveals that 67 characteristics of the smears are capable for describing the structure of smears in general. The Third stage of system concerns the Selection of Best Characteristics. Due to the high number of attributes (67 per case), it was essential to eliminate the characteristics that are connected linearly or do not bring diagnostics information. The choice of characteristics applied before the classification, having the aim of discovering a subset of characteristics that optimizes the process of classification. The technique of Sequential Float Forward Search (SFFS) was applied. The number of patients that used was 2,036 (1886 non malignancies and 150 malignancies). Among them all malignancies were histologically confirmed. In addition to that 140 no malignancies were histologically confirmed in correlation to evaluation of clinics, laboratorial and medical image actions (ultrasounds etc.). Among 2.036 smears the 25% used for characteristics selection, 37 smears of Malignant and smears of Non Malignant. The Sequential Float Forward Search (SFFS) Technique, choose the best 12 elements that they reveal high performance to FNA data categorization. The Fourth stage is the Application of Classification using Data Mining Methods or in other words data mining method. For this aim a set of reliable, well confirmed but also modern methods applied. In addition to that the system was trained and was checked using the sample with histological verifications (ground truth). The independent application of four reliable methods, Decision Trees, Artificial Neural Network, Support Vector Machine, and k-NN, resulting to comparable outcomes concerning those of FNA. However, further improvement was achieved with the application of Majority (Majority Vote - CMV) using of previous results of three algorithms Artificial Neural Network, Support Vector Machine, and k-NN. The modified Artificial Immune System (AIS) was applied for first time. AIS presents particularly improved results for the categorization of smears, which are characterised “suspicious” by the experts and is a known weakness of FNA method. These cases constitute a very difficult part for the discrimination among non-malignant and malignant, even for a specialist. Since all these cases are faced clinically using FNA as malignancies, the application of an improved algorithmic method improves accordingly the management of these cases by decreasing the number of useless surgical thyroid operations.

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