Graph theory reveals dysconnected hubs in 22q11DS and altered nodal efficiency in patients with hallucinations.

Schizophrenia is postulated to be the prototypical dysconnection disorder, in which hallucinations are the core symptom. Due to high heterogeneity in methodology across studies and the clinical phenotype, it remains unclear whether the structural brain dysconnection is global or focal and if clinical symptoms result from this dysconnection. In the present work, we attempt to clarify this issue by studying a population considered as a homogeneous genetic sub-type of schizophrenia, namely the 22q11.2 deletion syndrome (22q11.2DS). Cerebral MRIs were acquired for 46 patients and 48 age and gender matched controls (aged 6-26, respectively mean age = 15.20 ± 4.53 and 15.28 ± 4.35 years old). Using the Connectome mapper pipeline (connectomics.org) that combines structural and diffusion MRI, we created a whole brain network for each individual. Graph theory was used to quantify the global and local properties of the brain network organization for each participant. A global degree loss of 6% was found in patients' networks along with an increased Characteristic Path Length. After identifying and comparing hubs, a significant loss of degree in patients' hubs was found in 58% of the hubs. Based on Allen's brain network model for hallucinations, we explored the association between local efficiency and symptom severity. Negative correlations were found in the Broca's area (p < 0.004), the Wernicke area (p < 0.023) and a positive correlation was found in the dorsolateral prefrontal cortex (DLPFC) (p < 0.014). In line with the dysconnection findings in schizophrenia, our results provide preliminary evidence for a targeted alteration in the brain network hubs' organization in individuals with a genetic risk for schizophrenia. The study of specific disorganization in language, speech and thought regulation networks sharing similar network properties may help to understand their role in the hallucination mechanism.

Objectives and motivations of small-scale forest owners : theoretical modelling and qualitative assessment

Abstract

Place branding : a conceptual and theoretical framework

Within the context of rising competition between territories, identity has become the most important element of recognition, differentiation and commodification in the communicative process within which cities, regions and countries position themselves. Geographical spaces thus compete in terms of this identity, which is then subjected to fierce comparison and competition (Nogué, 1999; Anholt, 2007a). The territorial brand thus entails the reinvention of places through a process of brand construction (branding) based on the promotion of the individual and collective identities of geographical spaces; these identities, in turn, are imbued with the intangible factors associated with their respective territorial identities.

Application of theoretical models to financial innovation

The present paper is aimed at providing a general strategic overview of the existing theoretical models that have applications in the field of financial innovation. Whereas most financialdevelopments have relied upon traditional economic tools, a new stream of research is defining a novel paradigm in which mathematical models from diverse scientific disciplines are being applied to conceptualize and explain economic and financial behavior. Indeed, terms such as ‘econophysics’ or ‘quantum finance’ have recently appeared to embrace efforts in this direction. As a first contact with such research, the project will present a brief description of some of the main theoretical models that have applications in finance and economics, and will try to present, if possible, potential new applications to particular areas in financial analysis, or new applicable models. As a result, emphasiswill be put on the implications of this research for the financial sector and its future dynamics.

Maintenance of polymorphism : a theoretical approach using multilocus systems

Résumé La thématique de cette thèse peut être résumée par le célèbre paradoxe de biologie évolutive sur le maintien du polymorphisme face à la sélection et par l'équation du changement de fréquence gamétique au cours du temps dû, à la sélection. La fréquence d'un gamète xi à la génération (t + 1) est: !!!Equation tronquée!!! Cette équation est utilisée pour générer des données utlisée tout au long de ce travail pour 2, 3 et 4 locus dialléliques. Le potentiel de l'avantage de l'hétérozygote pour le maintien du polymorphisme est le sujet de la première partie. La définition commune de l'avantage de l'hétérozygote n'etant applicable qu'a un locus ayant 2 allèles, cet avantage est redéfini pour un système multilocus sur les bases de précédentes études. En utilisant 5 définitions différentes de l'avantage de l'hétérozygote, je montre que cet avantage ne peut être un mécanisme général dans le maintien du polymorphisme sous sélection. L'étude de l'influence de locus non-détectés sur les processus évolutifs, seconde partie de cette thèse, est motivée par les travaux moléculaires ayant pour but de découvrir le nombre de locus codant pour un trait. La plupart de ces études sous-estiment le nombre de locus. Je montre que des locus non-détectés augmentent la probabilité d'observer du polymorphisme sous sélection. De plus, les conclusions sur les facteurs de maintien du polymorphisme peuvent être trompeuses si tous les locus ne sont pas détectés. Dans la troisième partie, je m'intéresse à la valeur attendue de variance additive après un goulot d'étranglement pour des traits sélectionés. Une études précédente montre que le niveau de variance additive après goulot d'étranglement augmente avec le nombre de loci. Je montre que le niveau de variance additive après un goulot d'étranglement augmente (comparé à des traits neutres), mais indépendamment du nombre de loci. Par contre, le taux de recombinaison a une forte influence, entre autre en regénérant les gamètes disparus suite au goulot d'étranglement. La dernière partie de ce travail de thèse décrit un programme pour le logiciel de statistique R. Ce programme permet d'itérer l'équation ci-dessus en variant les paramètres de sélection, recombinaison et de taille de populations pour 2, 3 et 4 locus dialléliques. Cette thèse montre qu'utiliser un système multilocus permet d'obtenir des résultats non-conformes à ceux issus de systèmes rnonolocus (la référence en génétique des populations). Ce programme ouvre donc d'intéressantes perspectives en génétique des populations. Abstract The subject of this PhD thesis can be summarized by one famous paradox of evolu-tionary biology: the maintenance of polymorphism in the face of selection, and one classical equation of theoretical population genetics: the changes in gametic frequencies due to selection and recombination. The frequency of gamete xi at generation (t + 1) is given by: !!! Truncated equation!!! This equation is used to generate data on selection at two, three, and four diallelic loci for the different parts of this work. The first part focuses on the potential of heterozygote advantage to maintain genetic polymorphism. Results of previous studies are used to (re)define heterozygote advantage for multilocus systems, since the classical definition is for one diallelic locus. I use 5 different definitions of heterozygote advantage. And for these five definitions, I show that heterozygote advantage is not a general mechanism for the maintenance of polymorphism. The study of the influence of undetected loci on evolutionary processes (second part of this work) is motivated by molecular works which aim at discovering the loci coding for a trait. For most of these works, some coding loci remains undetected. I show that undetected loci increases the probability of maintaining polymorphism under selection. In addition, conclusions about the factor that maintain polymorphism can be misleading if not all loci are considered. This is, therefore, only when all loci are detected that exact conclusions on the level of maintained polymorphism or on the factor(s) that maintain(s) polymorphism could be drawn. In the third part, the focus is on the expected release of additive genetic variance after bottleneck for selected traits. A previous study shows that the expected release of additive variance increases with an increase in the number of loci. I show that the expected release of additive variance after bottleneck increases for selected traits (compared with neutral), but this increase is not a function of the number of loci, but function of the recombination rate. Finally, the last part of this PhD thesis is a description of a package for the statistical software R that implements the Equation given above. It allows to generate data for different scenario regarding selection, recombination, and population size. This package opens perspectives for the theoretical population genetics that mainly focuses on one locus, while this work shows that increasing the number of loci leads not necessarily to straightforward results.

Comparing Random-based and k-Anonymity-Based Algorithms for Graph Anonymization

Recently, several anonymization algorithms have appeared for privacy preservation on graphs. Some of them are based on random-ization techniques and on k-anonymity concepts. We can use both of them to obtain an anonymized graph with a given k-anonymity value. In this paper we compare algorithms based on both techniques in orderto obtain an anonymized graph with a desired k-anonymity value. We want to analyze the complexity of these methods to generate anonymized graphs and the quality of the resulting graphs.

Uncovering the genetic basis of adaptive change: on the intersection of landscape genomics and theoretical population genetics

A workshop recently held at the Ecole Polytechnique Federale de Lausanne (EPFL, Switzerland) was dedicated to understanding the genetic basis of adaptive change, taking stock of the different approaches developed in theoretical population genetics and landscape genomics and bringing together knowledge accumulated in both research fields. Indeed, an important challenge in theoretical population genetics is to incorporate effects of demographic history and population structure. But important design problems (e.g. focus on populations as units, focus on hard selective sweeps, no hypothesis-based framework in the design of the statistical tests) reduce their capability of detecting adaptive genetic variation. In parallel, landscape genomics offers a solution to several of these problems and provides a number of advantages (e.g. fast computation, landscape heterogeneity integration). But the approach makes several implicit assumptions that should be carefully considered (e.g. selection has had enough time to create a functional relationship between the allele distribution and the environmental variable, or this functional relationship is assumed to be constant). To address the respective strengths and weaknesses mentioned above, the workshop brought together a panel of experts from both disciplines to present their work and discuss the relevance of combining these approaches, possibly resulting in a joint software solution in the future.

Validation des SCORES cliniques: notions théoriques et pratiques de base. [Validation of clinical scores: theoretical and practical basic notions].

Chaque jour, le médecin utilise dans sa pratique des scores cliniques. Ces scores sont souvent des aides à la décision médicale. Les étapes de validation des scores cliniques sont par contre souvent méconnues du médecin. Cette revue rappelle les bases théoriques de la validation d'un score clinique et propose des exercices pratiques. [Abstract] Physicians are using clinical scores on a regular basis. These scores are generally helpful in making medical decisions. However, the process of validation of clinical scores is often unknown to the physicians. This paper reviews the theory of validation of clinical scores and proposes practical exercises.

Cancer chronotherapeutics: experimental, theoretical, and clinical aspects.

The circadian timing system controls cell cycle, apoptosis, drug bioactivation, and transport and detoxification mechanisms in healthy tissues. As a consequence, the tolerability of cancer chemotherapy varies up to several folds as a function of circadian timing of drug administration in experimental models. Best antitumor efficacy of single-agent or combination chemotherapy usually corresponds to the delivery of anticancer drugs near their respective times of best tolerability. Mathematical models reveal that such coincidence between chronotolerance and chronoefficacy is best explained by differences in the circadian and cell cycle dynamics of host and cancer cells, especially with regard circadian entrainment and cell cycle variability. In the clinic, a large improvement in tolerability was shown in international randomized trials where cancer patients received the same sinusoidal chronotherapy schedule over 24h as compared to constant-rate infusion or wrongly timed chronotherapy. However, sex, genetic background, and lifestyle were found to influence optimal chronotherapy scheduling. These findings support systems biology approaches to cancer chronotherapeutics. They involve the systematic experimental mapping and modeling of chronopharmacology pathways in synchronized cell cultures and their adjustment to mouse models of both sexes and distinct genetic background, as recently shown for irinotecan. Model-based personalized circadian drug delivery aims at jointly improving tolerability and efficacy of anticancer drugs based on the circadian timing system of individual patients, using dedicated circadian biomarker and drug delivery technologies.

The environmental effectiviness of alternative agri-environmental policy reforms : theoretical and empirical analysis

Selostus: Maatalouden ympäristöpolitiikan reformien tehokkuus ravinnepäästöjen vähentämisessä - teoreettinen ja empiirinen analyysi

Selection of the most informative morphoagronomic descriptors for cassava germplasm

The objective of this work was to select the most informative morphoagronomic descriptors for cassava (Manihot esculenta) germplasm and to evaluate the ability of different methods to select the descriptors. Ninety-five accessions were characterized using 51 morphoagronomic descriptors. Data were subjected to a multiple correspondence analysis (MCA), whose information was used in the following four methods of descriptor selection: reverse order of the descriptor for the pth factorial axis of the MCA (Jolliffe); sequential, multiple correspondence analysis (SMCA); mean of the contribution orders of the descriptor in the first three factorial axes (C3PA); and C3PA method weighted by the respective eigenvalues of the full analysis (C3PAWeig). The correlations between the dissimilarity matrix with all descriptors and the most informative descriptors were high and significant (0.75, 0.77, 0.83, and 0.84 for C3PAWeig, C3PA, SMCA, and Jolliffe, respectively). The less informative descriptors were discarded, considering those common among the selection methods and relevant for the breeding interests. Therefore, 32 morphoagronomic descriptors with correlation between the dissimilarity matrices (r=0.81) were selected, due to their high capacity to discriminate cassava germplasm and to their ability to maintain some preliminary agronomic traits, useful for the initial characterization of the germplasm.