941 resultados para Multi-Criteria Optimisation
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The objective of the research is to know the factors that in Spain determine the choice of banking organization. The obtained results indicate that the dimension of the network of branches is the reason more valued. In spite of the increasing symmetry of the Spanish banking market, the preferences of the clients of the savings banks and those of the banks are not absolutely coincident, being the proximity - the main reason for election- much more valued by the former than by the latter. The existence of divergences in the preferences has also been detected according to the region and the typology of city of residence.
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BACKGROUND: Mild cognitive impairment (MCI) has been defined as a transitional state between normal aging and dementia. In many cases, MCI represents an early stage of developing cognitive impairment. Patients diagnosed with MCI do not meet the criteria for dementia as their general intellect and everyday activities are preserved, although minor changes in instrumental activities of daily living (ADL) may occur. However, they may exhibit significant behavioral and psychological signs and symptoms (BPS), also frequently observed in patients with Alzheimer's disease (AD). Hence, we wondered to what extent specific BPS are associated with cognitive decline in participants with MCI or AD. METHODS: Our sample consisted of 164 participants, including 46 patients with amnestic (single or multi-domain) MCI and 54 patients with AD, as well as 64 control participants without cognitive disorders. Global cognitive performance, BPS, and ADL were assessed using validated clinical methods at baseline and at two-year follow-up. RESULTS: The BPS variability over the follow-up period was more pronounced in the MCI group than in patients with AD: some BPS improve, others occur newly or worsen, while others still remain unchanged. Moreover, specific changes in BPS were associated with a rapid deterioration of the global cognitive level in MCI patients. In particular, an increase of euphoria, eating disorders, and aberrant motor behavior, as well as worsened sleep quality, predicted a decline in cognitive functioning. CONCLUSIONS: Our findings confirm a higher variability of BPS over time in the MCI group than in AD patients. Moreover, our results provide evidence of associations between specific BPS and cognitive decline in the MCI group that might suggest a risk of conversion of individuals with amnestic MCI to AD.
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OBJECTIVES: To develop data-driven criteria for clinically inactive disease on and off therapy for juvenile dermatomyositis (JDM). METHODS: The Paediatric Rheumatology International Trials Organisation (PRINTO) database contains 275 patients with active JDM evaluated prospectively up to 24 months. Thirty-eight patients off therapy at 24 months were defined as clinically inactive and included in the reference group. These were compared with a random sample of 76 patients who had active disease at study baseline. Individual measures of muscle strength/endurance, muscle enzymes, physician's and parent's global disease activity/damage evaluations, inactive disease criteria derived from the literature and other ad hoc criteria were evaluated for sensitivity, specificity and Cohen's κ agreement. RESULTS: The individual measures that best characterised inactive disease (sensitivity and specificity >0.8 and Cohen's κ >0.8) were manual muscle testing (MMT) ≥78, physician global assessment of muscle activity=0, physician global assessment of overall disease activity (PhyGloVAS) ≤0.2, Childhood Myositis Assessment Scale (CMAS) ≥48, Disease Activity Score ≤3 and Myositis Disease Activity Assessment Visual Analogue Scale ≤0.2. The best combination of variables to classify a patient as being in a state of inactive disease on or off therapy is at least three of four of the following criteria: creatine kinase ≤150, CMAS ≥48, MMT ≥78 and PhyGloVAS ≤0.2. After 24 months, 30/31 patients (96.8%) were inactive off therapy and 69/145 (47.6%) were inactive on therapy. CONCLUSION: PRINTO established data-driven criteria with clearly evidence-based cut-off values to identify JDM patients with clinically inactive disease. These criteria can be used in clinical trials, in research and in clinical practice.
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We consider a principal who deals with a privately informed agent protected by limited liability in a correlated information setting. The agent's technology is such that the fixed cost declines with the marginal cost (the type), so that countervailing incentives may arise. We show that, with high liability, the first-best outcome can be effected for any type if (1) the fixed cost is non-concave in type, under the contract that yields the smallest feasible loss to the agent; (2) the fixed cost is not very concave in type, under the contract that yields the maximum sustainable loss to the agent. We further show that, with low liability, the first-best outcome is still implemented for a non-degenerate range of types if the fixed cost is less concave in type than some given threshold, which tightens as the liability reduces. The optimal contract entails pooling otherwise.
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Este trabajo presenta un sistema para detectar y clasificar objetos binarios según la forma de éstos. En el primer paso del procedimiento, se aplica un filtrado para extraer el contorno del objeto. Con la información de los puntos de forma se obtiene un descriptor BSM con características altamente descriptivas, universales e invariantes. En la segunda fase del sistema se aprende y se clasifica la información del descriptor mediante Adaboost y Códigos Correctores de Errores. Se han usado bases de datos públicas, tanto en escala de grises como en color, para validar la implementación del sistema diseñado. Además, el sistema emplea una interfaz interactiva en la que diferentes métodos de procesamiento de imágenes pueden ser aplicados.
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In recent years, multi-atlas fusion methods have gainedsignificant attention in medical image segmentation. Inthis paper, we propose a general Markov Random Field(MRF) based framework that can perform edge-preservingsmoothing of the labels at the time of fusing the labelsitself. More specifically, we formulate the label fusionproblem with MRF-based neighborhood priors, as an energyminimization problem containing a unary data term and apairwise smoothness term. We present how the existingfusion methods like majority voting, global weightedvoting and local weighted voting methods can be reframedto profit from the proposed framework, for generatingmore accurate segmentations as well as more contiguoussegmentations by getting rid of holes and islands. Theproposed framework is evaluated for segmenting lymphnodes in 3D head and neck CT images. A comparison ofvarious fusion algorithms is also presented.
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NORTH SEA STUDY OCCASIONAL PAPER No. 112
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Two logically distinct and permissive extensions of iterative weak dominance are introduced for games with possibly vector-valued payoffs. The first, iterative partial dominance, builds on an easy-to check condition but may lead to solutions that do not include any (generalized) Nash equilibria. However, the second and intuitively more demanding extension, iterative essential dominance, is shown to be an equilibrium refinement. The latter result includes Moulin’s (1979) classic theorem as a special case when all players’ payoffs are real-valued. Therefore, essential dominance solvability can be a useful solution concept for making sharper predictions in multicriteria games that feature a plethora of equilibria.
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Les progrès de la thérapie antirétrovirale ont transformé l'infection par le VIH d'une condition inévitablement fatale à une maladie chronique. En dépit de ce succès, l'échec thérapeutique et la toxicité médicamenteuse restent fréquents. Une réponse inadéquate au traitement est clairement multifactorielle et une individualisation de la posologie des médicaments qui se baserait sur les facteurs démographiques et génétiques des patients et sur les taux sanguins totaux, libres et/ou cellulaires des médicaments pourrait améliorer à la fois l'efficacité et la tolérance de la thérapie, cette dernière étant certainement un enjeu majeur pour un traitement qui se prend à vie.L'objectif global de cette thèse était de mieux comprendre les facteurs pharmacocinétiques (PK) et pharmacogénétiques (PG) influençant l'exposition aux médicaments antirétroviraux (ARVs) nous offrant ainsi une base rationnelle pour l'optimisation du traitement antiviral et pour l'ajustement posologique des médicaments chez les patients VIH-positifs. Une thérapie antirétrovirale adaptée au patient est susceptible d'augmenter la probabilité d'efficacité et de tolérance à ce traitement, permettant ainsi une meilleure compliance à long terme, et réduisant le risque d'émergence de résistance et d'échec thérapeutique.A cet effet, des méthodes de quantification des concentrations plasmatiques totales, libres et cellulaires des ARVs ainsi que de certains de leurs métabolites ont été développées et validées en utilisant la chromatographie liquide coupée à la spectrométrie de masse en tandem. Ces méthodes ont été appliquées pour la surveillance des taux d'ARVs dans diverses populations de patients HIV-positifs. Une étude clinique a été initiée dans le cadre de l'étude VIH Suisse de cohorte mère-enfant afin de déterminer si la grossesse influence la cinétique des ARVs. Les concentrations totales et libres du lopînavir, de l'atazanavir et de la névirapine ont été déterminées chez les femmes enceintes suivies pendant leur grossesse, et celles-ci ont été trouvées non influencées de manière cliniquement significative par la grossesse. Un ajustement posologique de ces ARVs n'est donc pas nécessaire chez les femmes enceintes. Lors d'une petite étude chez des patients HIV- positifs expérimentés, la corrélation entre l'exposition cellulaire et plasmatique des nouveaux ARVs, notamment le raltégravir, a été déterminée. Une bonne corrélation a été obtenue entre taux plasmatiques et cellulaires de raltégravir, suggérant que la surveillance des taux totaux est un substitut satisfaisant. Cependant, une importante variabilité inter¬patient a été observée dans les ratios d'accumulation cellulaire du raltégravir, ce qui devrait encourager des investigations supplémentaires chez les patients en échec sous ce traitement. L'efficacité du suivi thérapeutique des médicaments (TDM) pour l'adaptation des taux d'efavirenz chez des patients avec des concentrations au-dessus de la cible thérapeutique recommandée a été évaluée lors d'une étude prospective. L'adaptation des doses d'efavirenz basée sur le TDM s'est montrée efficace et sûre, soutenant l'utilisation du TDM chez les patients avec concentrations hors cible thérapeutique. L'impact des polymorphismes génétiques des cytochromes P450 (CYP) 2B6, 2A6 et 3A4/5 sur la pharmacocinétique de l'efavirenz et de ces métabolites a été étudié : un modèle de PK de population intégrant les covariats génétiques et démographiques a été construit. Les variations génétiques fonctionnelles dans les voies de métabolisation principales (CYP2B6) et accessoires {CYP2A6et 3A4/S) de l'efavirenz ont un impact sur sa disposition, et peuvent mener à des expositions extrêmes au médicament. Un? ajustement des doses guidé par le TDM est donc recommandé chez ces patients, en accord avec les polymorphismes génétiques.Ainsi, nous avons démonté qu'en utilisant une approche globale tenant compte à la fois des facteurs PK et PG influençant l'exposition aux ARVs chez les patients infectés, il est possible, si nécessaire, d'individualiser la thérapie antirétrovirale dans des situations diverses. L'optimisation du traitement antirétroviral contribue vraisemblablement à une meilleure efficacité thérapeutique à iong terme tout en réduisant la survenue d'effets indésirables.Résumé grand publicOptimisation de la thérapie antirétrovirale: approches pharmacocinétiques et pharmacogénétiquesLes progrès effectués dans le traitement de l'infection par le virus de llmmunodéficienoe humaine acquise (VIH) ont permis de transformer une affection mortelle en une maladie chronique traitable avec des médicaments de plus en plus efficaces. Malgré ce succès, un certain nombre de patients ne répondent pas de façon optimale à leur traitement etyou souffrent d'effets indésirables médicamenteux entraînant de fréquentes modifications dans leur thérapie. Il a été possible de mettre en évidence que l'efficacité d'un traitement antirétroviral est dans la plupart des cas corrélée aux concentrations de médicaments mesurées dans le sang des patients. Cependant, le virus se réplique dans la cellule, et seule la fraction des médicaments non liée aux protéines du plasma sanguin peut entrer dans la cellule et exercer l'activité antirétrovirale au niveau cellulaire. Il existe par ailleurs une importante variabilité des concentrations sanguines de médicament chez des patients prenant pourtant la même dose de médicament. Cette variabilité peut être due à des facteurs démographiques et/ou génétiques susceptibles d'influencer la réponse au traitement antirétroviral.Cette thèse a eu pour objectif de mieux comprendre les facteurs pharmacologiques et génétiques influençant l'efficacité et ta toxicité des médicaments antirétroviraux, dans le but d'individualiser la thérapie antivirale et d'améliorer le suivi des patients HIV-positifs.A cet effet, des méthodes de dosage très sensibles ont été développées pour permettre la quantification des médicaments antirétroviraux dans le sang et les cellules. Ces méthodes analytiques ont été appliquées dans le cadre de diverses études cliniques réalisées avec des patients. Une des études cliniques a recherché s'il y avait un impact des changements physiologiques liés à la grossesse sur les concentrations des médicaments antirétroviraux. Nous avons ainsi pu démontrer que la grossesse n'influençait pas de façon cliniquement significative le devenir des médicaments antirétroviraux chez les femmes enceintes HIV- positives. La posologie de médicaments ne devrait donc pas être modifiée dans cette population de patientes. Par ailleurs, d'autres études ont portés sur les variations génétiques des patients influençant l'activité enzymatique des protéines impliquées dans le métabolisme des médicaments antirétroviraux. Nous avons également étudié l'utilité d'une surveillance des concentrations de médicament (suivi thérapeutique) dans le sang des patients pour l'individualisation des traitements antiviraux. Il a été possible de mettre en évidence des relations significatives entre l'exposition aux médicaments antirétroviraux et l'existence chez les patients de certaines variations génétiques. Nos analyses ont également permis d'étudier les relations entre les concentrations dans le sang des patients et les taux mesurés dans les cellules où le virus HIV se réplique. De plus, la mesure des taux sanguins de médicaments antirétroviraux et leur interprétation a permis d'ajuster la posologie de médicaments chez les patients de façon efficace et sûre.Ainsi, la complémentarité des connaissances pharmacologiques, génétiques et virales s'inscrit dans l'optique d'une stratégie globale de prise en charge du patient et vise à l'individualisation de la thérapie antirétrovirale en fonction des caractéristiques propres de chaque individu. Cette approche contribue ainsi à l'optimisation du traitement antirétroviral dans la perspective d'un succès du traitement à long terme tout en réduisant la probabilité des effets indésirables rencontrés. - The improvement in antirétroviral therapy has transformed HIV infection from an inevitably fatal condition to a chronic, manageable disease. However, treatment failure and drug toxicity are frequent. Inadequate response to treatment is clearly multifactorial and, therefore, dosage individualisation based on demographic factors, genetic markers and measurement of total, free and/or cellular drug level may increase both drug efficacy and tolerability. Drug tolerability is certainly a major issue for a treatment that must be taken indefinitely.The global objective of this thesis aimed at increasing our current understanding of pharmacokinetic (PK) and pharmacogenetic (PG) factors influencing the exposition to antirétroviral drugs (ARVs) in HIV-positive patients. In turn, this should provide us with a rational basis for antiviral treatment optimisation and drug dosage adjustment in HIV- positive patients. Patient's tailored antirétroviral regimen is likely to enhance treatment effectiveness and tolerability, enabling a better compliance over time, and hence reducing the probability of emergence of viral resistance and treatment failure.To that endeavour, analytical methods for the measurement of total plasma, free and cellular concentrations of ARVs and some of their metabolites have been developed and validated using liquid chromatography coupled with tandem mass spectrometry. These assays have been applied for the monitoring of ARVs levels in various populations of HIV- positive patients. A clinical study has been initiated within the frame of the Mother and Child Swiss HIV Cohort Study to determine whether pregnancy influences the exposition to ARVs. Free and total plasma concentrations of lopinavir, atazanavir and nevirapine have been determined in pregnant women followed during the course of pregnancy, and were found not influenced to a clinically significant extent by pregnancy. Dosage adjustment for these drugs is therefore not required in pregnant women. In a study in treatment- experienced HIV-positive patients, the correlation between cellular and total plasma exposure to new antirétroviral drugs, notably the HIV integrase inhibitor raltegravir, has been determined. A good correlation was obtained between total and cellular levels of raltegravir, suggesting that monitoring of total levels are a satisfactory. However, significant inter-patient variability was observed in raltegravir cell accumulation which should prompt further investigations in patients failing under an integrase inhibitor-based regimen. The effectiveness of therapeutic drug monitoring (TDM) to guide efavirenz dose reduction in patients having concentrations above the recommended therapeutic range was evaluated in a prospective study. TDM-guided dosage adjustment of efavirenz was found feasible and safe, supporting the use of TDM in patients with efavirenz concentrations above therapeutic target. The impact of genetic polymorphisms of cytochromes P450 (CYP) 2B6, 2A6 and 3A4/5 on the PK of efavirenz and its metabolites was studied: a population PK model was built integrating both genetic and demographic covariates. Functional genetic variations in main (CYP2B6) and accessory (2A6, 3A4/5) metabolic pathways of efavirenz have an impact on efavirenz disposition, and may lead to extreme drug exposures. Dosage adjustment guided by TDM is thus required in those patients, according to the pharmacogenetic polymorphism.Thus, we have demonstrated, using a comprehensive approach taking into account both PK and PG factors influencing ARVs exposure in HIV-infected patients, the feasibility of individualising antirétroviral therapy in various situations. Antiviral treatment optimisation is likely to increase long-term treatment success while reducing the occurrence of adverse drug reactions.
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In this study we propose an application of the MuSIASEM approach which is used to provide an integrated analysis of Laos across different scales. With the term “integrated analysis across scales” we mean the generation of a series of packages of quantitative indicators, characterizing the performance of the socioeconomic activities performed in Laos when considering: (i) different hierarchical levels of organization (farming systems described at the level of household, rural villages, regions of Laos, the whole country level); and (ii) different dimensions of analysis (economic dimension, social dimension, ecological dimension, technical dimension). What is relevant in this application is that the information carried out by these different packages of indicators is integrated in a system of accounting which establishes interlinkages across these indicators. This is a essential feature to study sustainability trade-offs and to build more robust scenarios of possible changes. The multi-scale integrated representation presented in this study is based on secondary data (gathered in a three year EU project – SEAtrans and integrated by other available statistical sources) and it is integrated in GIS, when dealing with the spatial representation of Laos. However, even if we use data referring to Laos, the goal of this study is not that of providing useful information about a practical policy issue of Laos, but rather, to illustrate the possibility of using a multipurpose grammar to produce an integrated set of sustainability indicators at three different levels: (i) local; (ii) meso; (iii) macro level. The technical issue addressed is the simultaneous adoption of two multi-level matrices – one referring to a characterization of human activity over a set of different categories, and another referring to a characterization of land uses over the same set of categories. In this way, it becomes possible to explain the characteristics of Laos (an integrated set of indicators defining the performance of the whole country) in relation to the characteristics of the rural Laos and urban Laos. The characteristics of rural Laos, can be explained using the characteristics of three regions defined within Laos (Northern Laos, Central Laos and Southern Laos), which in turn can be defined (using an analogous package of indicators), starting from the characteristics of three main typologies of farming systems found in the regions.
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This study presents a first attempt to extend the “Multi-scale integrated analysis of societal and ecosystem metabolism (MuSIASEM)” approach to a spatial dimension using GIS techniques in the Metropolitan area of Barcelona. We use a combination of census and commercial databases along with a detailed land cover map to create a layer of Common Geographic Units that we populate with the local values of human time spent in different activities according to MuSIASEM hierarchical typology. In this way, we mapped the hours of available human time, in regards to the working hours spent in different locations, putting in evidence the gradients in spatial density between the residential location of workers (generating the work supply) and the places where the working hours are actually taking place. We found a strong three-modal pattern of clumps of areas with different combinations of values of time spent on household activities and on paid work. We also measured and mapped spatial segregation between these two activities and put forward the conjecture that this segregation increases with higher energy throughput, as the size of the functional units must be able to cope with the flow of exosomatic energy. Finally, we discuss the effectiveness of the approach by comparing our geographic representation of exosomatic throughput to the one issued from conventional methods.
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Background: Distinguishing postmortem gas accumulations in the body due to natural decomposition and other phenomena such as gas embolism can prove a difficult task using purely Multi-Detector Computed Tomography (MDCT). The Radiological Alteration Index (RAI) was created with the intention to be able to identify bodies undergoing the putrefaction process based on the quantity of gas detected within the body. The flaw in this approach is the inability to absolutely determine putrefaction as the origin of gas volumes in cases of moderate alteration. The aim of the current study is to identify percentage compositions of O2, N2, CO2 and the presence of gases such as H2 and H2S within these sampling sites in order to resolve this complication. Materials and methods: All cases investigated in our University Center of Legal Medicine are undergoing a Post-Mortem Computed Tomography (PMCT)-scan before external examination or autopsy as a routine investigation. In the obtained images, areas of gas were characterized as 0, I, II or III based on the amount of gas present according to the RAI (1). The criteria for these characterizations were dependent of the site of gas, for example thoracic and abdominal cavities were graded as I (1 - 3cm gas), II (3 - 5cm gas) and III (>5cm gas). Cases showing gaseous sites with grade II or III were selected for this study. The sampling was performed under CT-guidance to target the regions to be punctured. Luer-lock PTFE syringes equipped with a three-way valve and needles were used to sample the gas directly (2). Gaseous samples were then analysed using gas chromatography coupled to a thermal conductivity detector (GC-TCD). The components present in the samples were expressed as a percentage of the overall gas present. Results: Up to now, we have investigated more than 40 cases using our standardized procedure for sampling and analysis of gas. O2, N2 and CO2 were present in most samples. The following distributions were found to correlate to gas origins of gas embolism/scuba diving accidents, trauma and putrefaction: ? Putrefaction → O2 = 1 - 5%; CO2 > 15%; N2 = 10 - 70%; H2 / H2S / CH4 variable presence ? Gas embolism/Scuba diving accidents → O2 and N2= varying percentages; CO2 > 20% ? Trauma → O2 = small percentage; CO2 < 15%; N2 > 65% H2 and H2S indicated levels of putrefaction along with methane which can also gauge environmental conditions or conditions of body storage/burial. Many cases showing large RAI values (advanced alteration) did reveal a radiological diagnosis which was in concordance with the interpretation of the gas composition. However, in certain cases (gas embolism, scuba divers) radiological interpretation was not possible and only chemical gas analysis was found to lead to the correct diagnosis, meaning that it provided complementary information to the radiological diagnosis. Conclusion: Investigation of postmortem gases is a useful tool to determine origin of gas generation which can aid the diagnosis of the cause of death. Levels of gas can provide information on stage of putrefaction and help to perform essential medico-legal diagnosis such as vital gas embolism.
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To compare the impact of meeting specific classification criteria [modified New York (mNY), European Spondyloarthropathy Study Group (ESSG), and Assessment of SpondyloArthritis international Society (ASAS) criteria] on anti-tumor necrosis factor (anti-TNF) drug retention, and to determine predictive factors of better drug survival. All patients fulfilling the ESSG criteria for axial spondyloarthritis (SpA) with available data on the axial ASAS and mNY criteria, and who had received at least one anti-TNF treatment were retrospectively retrieved in a single academic institution in Switzerland. Drug retention was computed using survival analysis (Kaplan-Meier), adjusted for potential confounders. Of the 137 patients classified as having axial SpA using the ESSG criteria, 112 also met the ASAS axial SpA criteria, and 77 fulfilled the mNY criteria. Drug retention rates at 12 and 24 months for the first biologic therapy were not significantly different between the diagnostic groups. Only the small ASAS non-classified axial SpA group (25 patients) showed a nonsignificant trend toward shorter drug survival. Elevated CRP level, but not the presence of bone marrow edema on magnetic resonance imaging (MRI) scans, was associated with significantly better drug retention (OR 7.9, ICR 4-14). In this cohort, anti-TNF drug survival was independent of the classification criteria. Elevated CRP level, but not positive MRI, was associated with better drug retention.