Early adversity and 5-HTT-BDNF genes: New evidences of Gene-Environment interactions on depressive symptoms in a general population

Background Adverse childhood experiences have been described as one of the major environmental risk factors for depressive disorder. Similarly, the deleterious impact of early traumatic experiences on depression seems to be moderated by individual genetic variability. Serotonin transporter (5-HTT) and brain-derived neurotrophic factor (BDNF) modulate the effect of childhood adversity on adult depression, although inconsistencies across studies have been found. Moreover, the gene×environment (G×E) interaction concerning the different types of childhood adversity remains poorly understood. The aim of this study was to analyse the putative interaction between the 5-HTT gene (5-HTTLPR polymorphism), the BDNF gene (Val66Met polymorphism) and childhood adversity in accounting for adult depressive symptoms. Method A sample of 534 healthy individuals filled in self-report questionnaires of depressive symptomatology [the Symptom Check List 90 Revised (SCL-90-R)] and different types of childhood adversities [the Childhood Trauma Questionnaire (CTQ)]. The 5-HTTLPR polymorphism (5-HTT gene) and the Val66Met polymorphism (BDNF gene) were genotyped in the whole sample. Results Total childhood adversity (β=0.27, p<0.001), childhood sexual abuse (CSA; β=0.17, p<0.001), childhood emotional abuse (β=0.27, p<0.001) and childhood emotional neglect (β=0.22, p<0.001) had an impact on adult depressive symptoms. CSA had a greater impact on depressive symptoms in Met allele carriers of the BDNF gene than in the Val/Val group (F=5.87, p<0.0001), and in S carriers of the 5-HTTLPR polymorphism (5-HTT gene) (F=5.80, p<0.0001). Conclusions Childhood adversity per se predicted higher levels of adult depressive symptoms. In addition, BDNF Val66Met and 5-HTTLPR polymorphisms seemed to moderate the effect of CSA on adult depressive symptoms.

Non-thermal emission from microquasar/ISM interaction

Context. The interaction of microquasar jets with their environment can produce non-thermal radiation as in the case of extragalactic outflows impacting on their surroundings. Significant observational evidence of jet/medium interaction in galactic microquasars has been collected in the past few years, although little theoretical work has been done regarding the resulting non-thermal emission. Aims. In this work, we investigate the non-thermal emission produced in the interaction between microquasar jets and their environment, and the physical conditions for its production. Methods. We developed an analytical model based on those successfully applied to extragalactic sources. The jet is taken to be a supersonic and mildly relativistic hydrodynamical outflow. We focus on the jet/shocked medium structure in its adiabatic phase, and assume that it grows in a self-similar way. We calculate the fluxes and spectra of the radiation produced via synchrotron, inverse Compton, and relativistic bremsstrahlung processes by electrons accelerated in strong shocks. A hydrodynamical simulation is also performed to investigate further the jet interaction with the environment and check the physical parameters used in the analytical model. Results. For reasonable values of the magnetic field, and using typical values of the external matter density, the non-thermal particles could produce significant amounts of radiation at different wavelengths, although they do not cool primarily radiatively, but by adiabatic losses. The physical conditions of the analytical jet/medium interaction model are consistent with those found in the hydrodynamical simulation. Conclusions. Microquasar jet termination regions could be detectable at radio wavelengths for current instruments sensitive to ~arcminute scales. At X-ray energies, the expected luminosities are moderate, although the emitter is more compact than the radio one. The source may be detectable by XMM-Newton or Chandra, with 1-10 arcsec of angular resolution. The radiation at gamma-ray energies may be within the detection limits of the next generation of satellite and ground-based instruments.

Computational and Experimental Investigation of the Grooved Roll in Paper Machine Environment

In the paper machine, it is not a desired feature for the boundary layer flows in the fabric and the roll surfaces to travel into the closing nips, creating overpressure. In this thesis, the aerodynamic behavior of the grooved roll and smooth rolls is compared in order to understand the nip flow phenomena, which is the main reason why vacuum and grooved roll constructions are designed. A common method to remove the boundary layer flow from the closing nip is to use the vacuum roll construction. The downside of the use of vacuum rolls is high operational costs due to pressure losses in the vacuum roll shell. The deep grooved roll has the same goal, to create a pressure difference over the paper web and keep the paper attached to the roll or fabric surface in the drying pocket of the paper machine. A literature review revealed that the aerodynamic functionality of the grooved roll is not very well known. In this thesis, the aerodynamic functionality of the grooved roll in interaction with a permeable or impermeable wall is studied by varying the groove properties. Computational fluid dynamics simulations are utilized as the research tool. The simulations have been performed with commercial fluid dynamics software, ANSYS Fluent. Simulation results made with 3- and 2-dimensional fluid dynamics models are compared to laboratory scale measurements. The measurements have been made with a grooved roll simulator designed for the research. The variables in the comparison are the paper or fabric wrap angle, surface velocities, groove geometry and wall permeability. Present-day computational and modeling resources limit grooved roll fluid dynamics simulations in the paper machine scale. Based on the analysis of the aerodynamic functionality of the grooved roll, a grooved roll simulation tool is proposed. The smooth roll simulations show that the closing nip pressure does not depend on the length of boundary layer development. The surface velocity increase affects the pressure distribution in the closing and opening nips. The 3D grooved roll model reveals the aerodynamic functionality of the grooved roll. With the optimal groove size it is possible to avoid closing nip overpressure and keep the web attached to the fabric surface in the area of the wrap angle. The groove flow friction and minor losses play a different role when the wrap angle is changed. The proposed 2D grooved roll simulation tool is able to replicate the grooved aerodynamic behavior with reasonable accuracy. A small wrap angle predicts the pressure distribution correctly with the chosen approach for calculating the groove friction losses. With a large wrap angle, the groove friction loss shows too large pressure gradients, and the way of calculating the air flow friction losses in the groove has to be reconsidered. The aerodynamic functionality of the grooved roll is based on minor and viscous losses in the closing and opening nips as well as in the grooves. The proposed 2D grooved roll model is a simplification in order to reduce computational and modeling efforts. The simulation tool makes it possible to simulate complex paper machine constructions in the paper machine scale. In order to use the grooved roll as a replacement for the vacuum roll, the grooved roll properties have to be considered on the basis of the web handling application.

Thalassemia intermedia as a result of heterozygosis for ß0-thalassemia and aaaanti-3.7/aa genotype in a Brazilian patient

We report a case in which the interaction of heterozygosis for both the ß0-IVS-II-1 (G->A) mutation and the aaaanti-3.7 allele was the probable cause for the clinical occurrence of thalassemia intermedia. The propositus, a 6-year-old Caucasian Brazilian boy of Portuguese descent, showed a moderately severe chronic anemia in spite of having the ß-thalassemia trait. Investigation of the alpha-globin gene status revealed heterozygosis for alpha-gene triplication (aaa/aa). The patient's father, also presenting mild microcytic and hypochromic anemia, had the same alpha and ß genotypes as his son, while the mother, not related to the father and hematologically normal, was also a carrier of the aaaanti-3.7 allele. The present case emphasizes the need for considering the possibility of alpha-gene triplication in ß-thalassemia heterozygotes who display an unexpected severe phenotype. The ß-thalassemia mutation found here is being described for the first time in Brazil.

Plant-Herbivore Interaction in a Fragmented Landscape: Local Adaptation and Inbreeding

Reciprocal selection between interacting species is a major driver of biodiversity at both the genetic and the species level. This reciprocal selection, or coevolution, has led to the diversification of two highly diverse and abundant groups of organisms, flowering plants and their insect herbivores. In heterogeneous environments, the outcome of coevolved species interactions is influenced by the surrounding community and/or the abiotic environment. The process of adaptation allows species to adapt to their local conditions and to local populations of interacting species. However, adaptation can be disrupted or slowed down by an absence of genetic variation or by increased inbreeding, together with the following inbreeding depression, both of which are common in small and isolated populations that occur in fragmented environments. I studied the interaction between a long-lived plant Vincetoxicum hirundinaria and its specialist herbivore Abrostola asclepiadis in the southwestern archipelago of Finland. I focused on mutual local adaptation of plants and herbivores, which is a demonstration of reciprocal selection between species, a prerequisite for coevolution. I then proceeded to investigate the processes that could potentially hamper local adaptation, or species interaction in general, when the population size is small. I did this by examining how inbreeding of both plants and herbivores affects traits that are important for interaction, as well as among-population variation in the effects of inbreeding. In addition to bi-parental inbreeding, in plants inbreeding can arise from self-fertilization which has important implications for mating system evolution. I found that local adaptation of the plant to its herbivores varied among populations. Local adaptation of the herbivore varied among populations and years, being weaker in populations that were most connected. Inbreeding caused inbreeding depression in both plants and herbivores. In some populations inbreeding depression in herbivore biomass was stronger in herbivores feeding on inbred plants than in those feeding on outbred ones. For plants it was the other way around: inbreeding depression in anti-herbivore resistance decreased when the herbivores were inbred. Underlying some of the among-population variation in the effects of inbreeding is variation in plant phenolic compounds. However, variation in the modification of phenolic compounds in the digestive tract of the herbivore did not explain the inbreeding depression in herbivore biomass. Finally, adult herbivores had a preference for outbred host plants for egg deposition, and herbivore inbreeding had a positive effect on egg survival when the eggs were exposed to predators and parasitoids. These results suggest that plants and herbivores indeed exert reciprocal selection, as demonstrated by the significant local adaptation of V. hirundinaria and A. asclepiadis to one another. The most significant cause of disruption of the local adaptation of herbivore populations was population connectivity, and thus probably gene flow. In plants local adaptation tended to increase with increasing genetic variation. Whether or not inbreeding depression occurred varied according to the life-history stage of the herbivore and/or the plant trait in question. In addition, the effects of inbreeding strongly depended on the population. Taken together, inbreeding modified plant-herbivore interactions at several different levels, and can thus affect the strength of reciprocal selection between species. Thus inbreeding has the potential to affect the outcome of coevolution.

Environment is crucial to the cooking time of beans

The objectives of this study were to understand how genotype, storage time, and storage conditions affect cooking time of beans and to indicate storage techniques that do not affect the cooking time. The grains were subjected to five different storage periods and six different storage conditions. The cooking time was estimated using the Mattson Cooker. The data were subjected to analysis of variance and a subsequent adjustment of simple linear regression for deployment of the interactions between the factors. Contrasts were used to determine the best levels of the factor storage condition. Genotype did not impact cooking time when the storage time and storage conditions were considered. Time and storage conditions affect the cooking time of beans in a dependent manner, but time of storage had the biggest influence. The best conditions for long-term storage of beans ensuring a smaller increase in cooking time is plastic storage at low temperatures. Thus, plastic freezer storage is a practical alternative for consumers.

Non-parametric stability analyses of dough properties in wheat

AbstractLiterature has unveiled that a paper has not been published yet on using non-parametric stability statistics (NPSSs) for evaluating genotypic stability in dough properties of wheat. Accordingly, the effects of genotype (G), environment (E) and GE interaction (GEI) on alveograph parameters, i.e. dough baking strength (W) and its tenacity (P)/extensibility (L), of 18 wheat (T. aestivum L.) genotypes were studied under irrigated field conditions in an 8-year trial (2006-2014) in central Turkey. Furthermore, genotypic stability for W and P/L was determined using 8 NPSSs viz. RM-Rank mean, RSD-Rank’s standard deviation, RS-Rank Sum, TOP-Ranking, Si(1), Si(2), Si(3) and Si(6) rank statistics. The ANOVA revealed that W and P/L were primarily controlled by E, although G and GEI also had significant effects. Among the 8 NPSSs, only RM, RS and TOP statistics were suitable for detecting the genotypes with high stable and bread making quality (e.g. G1 and G17). In conclusion, using RM, RS and TOP statistics is advisable to select for dough quality in wheat under multi-environment trials (METs).

Promoting Healthy Lifestyles with Personalized, APOE Genotype Based Health Information: The Effects on Psychological-, Health Behavioral and Clinical Factors

There is an increasing demand for individualized, genotype-based health advice. The general population-based dietary recommendations do not always motivate people to change their life-style, and partly following this, cardiovascular diseases (CVD) are a major cause of death in worldwide. Using genotype-based nutrition and health information (e.g. nutrigenetics) in health education is a relatively new approach, although genetic variation is known to cause individual differences in response to dietary factors. Response to changes in dietary fat quality varies, for example, among different APOE genotypes. Research in this field is challenging, because several non-modifiable (genetic, age, sex) and modifiable (e.g. lifestyle, dietary, physical activity) factors together and with interaction affect the risk of life-style related diseases (e.g. CVD). The other challenge is the psychological factors (e.g. anxiety, threat, stress, motivation, attitude), which also have an effect on health behavior. The genotype-based information is always a very sensitive topic, because it can also cause some negative consequences and feelings (e.g. depression, increased anxiety). The aim of this series of studies was firstly to study how individual, genotype-based health information affects an individual’s health form three aspects, and secondly whether this could be one method in the future to prevent lifestyle-related diseases, such as CVD. The first study concentrated on the psychological effects; the focus of the second study was on health behavior effects, and the third study concentrated on clinical effects. In the fourth study of this series, the focus was on all these three aspects and their associations with each other. The genetic risk and health information was the APOE gene and its effects on CVD. To study the effect of APOE genotype-based health information in prevention of CVD, a total of 151 volunteers attended the baseline assessments (T0), of which 122 healthy adults (aged 20 – 67 y) passed the inclusion criteria and started the one-year intervention. The participants (n = 122) were randomized into a control group (n = 61) and an intervention group (n = 61). There were 21 participants in the intervention Ɛ4+ group (including APOE genotypes 3/4 and 4/4) and 40 participants in the intervention Ɛ4- group (including APOE genotypes 2/3 and 3/3). The control group included 61 participants (including APOE genotypes 3/4, 4/4, 2/3, 3/3 and 2/2). The baseline (T0) and follow-up assessments (T1, T2, T3) included detailed measurements of psychological (threat and anxiety experience, stage of change), and behavioral (dietary fat quality, consumption of vegetables, - high fat/sugar foods and –alcohol, physical activity and health and taste attitudes) and clinical factors (total-, LDL- HDL cholesterol, triglycerides, blood pressure, blood glucose (0h and 2h), body mass index, waist circumference and body fat percentage). During the intervention six different communication sessions (lectures on healthy lifestyle and nutrigenomics, health messages by mail, and personal discussion with the doctor) were arranged. The intervention groups (Ɛ4+ and Ɛ4-) received their APOE genotype information and health message at the beginning of the intervention. The control group received their APOE genotype information after the intervention. For the analyses in this dissertation, the results for 106/107 participants were analyzed. In the intervention, there were 16 participants in the high-risk (Ɛ4+) group and 35 in the low-risk (Ɛ4-) group. The control group had 55 participants in studies III-IV and 56 participants in studies I-II. The intervention had both short-term (≤ 6 months) and long-term (12 months) effects on health behavior and clinical factors. The short-term effects were found in dietary fat quality and waist circumference. Dietary fat quality improved more in the Ɛ4+ group than the Ɛ4- and the control groups as the personal, genotype-based health information and waist circumference lowered more in the Ɛ4+ group compared with the control group. Both these changes differed significantly between the Ɛ4+ and control groups (p<0.05). A long-term effect was found in triglyceride values (p<0.05), which lowered more in Ɛ4+ compared with the control group during the intervention. Short-term effects were also found in the threat experience, which increased mostly in the Ɛ4+ group after the genetic feedback (p<0.05), but it decreased after 12 months, although remaining at a higher level compared to the baseline (T0). In addition, Study IV found that changes in the psychological factors (anxiety and threat experience, motivation), health and taste attitudes, and health behaviors (dietary, alcohol consumption, and physical activity) did not directly explain the changes in triglyceride values and waist circumference. However, change caused by a threat experience may have affected the change in triglycerides through total- and HDL cholesterol. In conclusion, this dissertation study has given some indications that individual, genotypebased health information could be one potential option in the future to prevent lifestyle-related diseases in public health care. The results of this study imply that personal genetic information, based on APOE, may have positive effects on dietary fat quality and some cardiovascular risk markers (e.g., improvement in triglyceride values and waist circumference). This study also suggests that psychological factors (e.g. anxiety and threat experience) may not be an obstacle for healthy people to use genotype-based health information to promote healthy lifestyles. However, even in the case of very personal health information, in order to achieve a permanent health behavior change, it is important to include attitudes and other psychological factors (e.g. motivation), as well as intensive repetition and a longer intervention duration. This research will serve as a basis for future studies and its information can be used to develop targeted interventions, including health information based on genotyping that would aim at preventing lifestyle diseases. People’s interest in personalized health advices has increased, while also the costs of genetic screening have decreased. Therefore, generally speaking, it can be assumed that genetic screening as a part of the prevention of lifestyle-related diseases may become more common in the future. In consequence, more research is required about how to make genetic screening a practical tool in public health care, and how to efficiently achieve long-term changes.

Federal-provincial relations and the environment : attaining sustainable development through cooperation /

A study of intergovernmental relations in the area of the environment will determine whether the current Canadian federal structure represents a dangerous impediment to the promotion of sustainable development. This paper examines the interjurisdictional quagmire that has developed from the fact that authority over the environment is a functionally concurrent field for the two orders of government. A history of federal-provincial relations in the area of environmental protection is followed by an analysis of the advantages and disadvantages associated with competitive and cooperative federalism. For the purpose of this paper, cooperative federalism is characterized by the presence of a formal institutional system to facilitate interaction between politicians and bureaucrats from both orders of government. Competitive federalism is defined as a system that lacks a formal institutional structure to promote discussion and coordination between federal and provincial officials in a specific field of interest. Last, I examine thirty sustainable development issues following the structure established in Agenda 21 to determine the impact of the present federal system on the development of these objectives. This study concludes that Canadian federalism is not a dangerous impediment to the promotion of sustainable development. Cooperative federalism in a form that does not eliminate the ability of governments to revert to competition promotes the emergence of an institutional system that facilitates information-sharing and discussion between the two orders of government, thus leading to coordinated efforts in the field of the environment. Respect for the current division of powers in this area is also essential to the cohesiveness of Canadian society. Policy-makers and advocates for a sustainable society should focus on working within the present system.

Job Demands and Organizational Citizenship Behavior: The Roles of Organizational Commitment and Social Interaction

Drawing from the Job Demands-Resources (JD-R) model and research on social exchange relationships, this study investigates the impact of three job demands (work overload, interpersonal conflict, and dissatisfaction with the organization’s current situation) on employees’ organizational citizenship behavior (OCB), the hitherto unexplored mediating role of organizational commitment in the link between job demands and organizational citizenship behavior (OCB), as well as how this mediating effect might be moderated by social interaction. Using a multi-source, two-wave research design, surveys were administered to 707 employees and their supervisors in a Mexican-based organization. The hypotheses were tested with hierarchical regression analysis. The results indicate a direct negative relationship between interpersonal conflict and OCB, and a mediating effect of organizational commitment for interpersonal conflict and dissatisfaction with the organization’s current situation. Further, social interaction moderates the mediating effect of organizational commitment for each of the three job demands such that the mediating effect is weaker at higher levels of social interaction. The study suggests that organizations aiming to instill OCB among their employees should match the immediate work context surrounding their task execution with an internal environment that promotes informal relationship building.

Virus-Host Interaction during Therapy against Hepatitis C Virus

Le virus de l’hépatite C (VHC) est un problème mondial. La majorité des personnes infectées (70-85%) développent une infection chronique qui cause des complications hépatiques. Le seul régime thérapeutique approuvé pour le VHC est l'interféron alpha (IFN-α). Ce traitement a un taux de réussite de 50-80% selon le génotype de virus et le moment de l'initiation de la thérapie. Les facteurs régissant la réponse au traitement ne sont pas bien définis. Des études antérieures ont suggéré un rôle potentiel de la réponse immunitaire de l'hôte au succès de la thérapie, toutefois, ces résultats sont controversés. Nous avons émis l'hypothèse que la réponse immunitaire de l’hôte sera plus efficace chez les patients qui commencent la thérapie tôt pendant la phase aiguë de l'infection. En revanche, la réponse immunitaire sera épuisée lorsque le traitement est initié pendant la phase chronique. L'objectif principal de ce mémoire est d’étudier les facteurs immunologiques qui régissent la réponse à la thérapie, et de déterminer si la contribution de la réponse immunitaire de l'hôte peut être influencée par la période de l'infection. Nos résultats démontrent l'efficacité de la restauration de la réponse immunitaire spécifique au VHC lorsque la thérapie par l'interféron est initiée tôt. Ceci est démontré par le sauvetage des cellules T efficaces spécifiques au VHC efficace similaires à celles observées chez les individus qui ont résolu spontanément, suggérant ainsi qu'elles jouent un rôle actif dans la réponse au traitement. Toutefois, cette réponse n'a pas été restaurée chez les patients traités au cours de la phase chronique. Ces résultats ont des implications importantes dans la compréhension des mécanismes sous-jacents à la réponse aux traitements actuels et au développement des nouvelles thérapies.

Study of baleen whales’ ecology and interaction with maritime traffic activities to support management of a complex socio-ecological system

Thesis written in co-mentorship with Robert Michaud.

Interaction d'Escherichia coli entérohémorragique (EHEC) avec Acanthamoeba castellanii et rôle du régulon Pho chez les EHEC

Les EHEC de sérotype O157:H7 sont des agents zoonotiques d’origine alimentaire ou hydrique. Ce sont des pathogènes émergeants qui causent chez l’humain des épidémies de gastro-entérite aiguë et parfois un syndrome hémolytique-urémique. Les EHEC réussissent leur transmission à l’humain à partir de leur portage commensal chez l’animal en passant par l’étape de survie dans l’environnement. L’endosymbiose microbienne est une des stratégies utilisées par les bactéries pathogènes pour survivre dans les environnements aquatiques. Les amibes sont des protozoaires vivants dans divers écosystèmes et connus pour abriter plusieurs agents pathogènes. Ainsi, les amibes contribueraient à transmettre les EHEC à l'humain. La première partie de mon projet de thèse est centrée sur l'interaction de l’amibe Acanthamoeba castellanii avec les EHEC. Les résultats montrent que la présence de cette amibe prolonge la persistance des EHEC, et ces dernières survivent à leur phagocytose par les amibes. Ces résultats démontrent le potentiel réel des amibes à héberger les EHEC et à contribuer à leur transmission. Cependant, l’absence de Shiga toxines améliore leur taux de survie intra-amibe. Par ailleurs, les Shiga toxines sont partiellement responsables de l’intoxication des amibes par les EHEC. Cette implication des Shiga toxines dans le taux de survie intracellulaire et dans la mortalité des amibes démontre l’intérêt d’utiliser les amibes comme modèle d'interaction hôte/pathogène pour étudier la pathogénicité des EHEC. Durant leur cycle de transmission, les EHEC rencontrent des carences en phosphate inorganique (Pi) dans l’environnement. En utilisant conjointement le système à deux composantes (TCS) PhoB-R et le système Pst (transport spécifique de Pi), les EHEC détectent et répondent à cette variation en Pi en activant le régulon Pho. La relation entre la virulence des EHEC, le PhoB-R-Pst et/ou le Pi environnemental demeure inconnue. La seconde partie de mon projet explore le rôle du régulon Pho (répondant à un stress nutritif de limitation en Pi) dans la virulence des EHEC. L’analyse transcriptomique montre que les EHEC répondent à la carence de Pi par une réaction complexe impliquant non seulement un remodelage du métabolisme général, qui est critique pour sa survie, mais aussi en coordonnant sa réponse de virulence. Dans ces conditions le régulateur PhoB contrôle directement l’expression des gènes du LEE et de l’opéron stx2AB. Ceci est confirmé par l’augmentation de la sécrétion de l’effecteur EspB et de la production et sécrétion de Stx2 en carence en Pi. Par ailleurs, l’activation du régulon Pho augmente la formation de biofilm et réduit la motilité chez les EHEC. Ceci corrèle avec l’induction des gènes régulant la production de curli et la répression de la voie de production d’indole et de biosynthèse du flagelle et du PGA (Polymère β-1,6-N-acétyle-D-glucosamine).

Interaction entre ventilation mécanique et traumatisme à la moelle épinière : réponses inflammatoires pulmonaires et médullaires

Le traumatisme de la moelle épinière est à l’origine d’une inflammation locale importante caractérisée par l’augmentation massive des cellules inflammatoires et la présence de réactions oxydatives. Cette inflammation locale peut déclencher une réponse inflammatoire systémique par voie hématogène. Au niveau cervical, les lésions médullaires peuvent entraîner des faiblesses ou la paralysie des muscles respiratoires. Le patient, qui ne peut plus respirer de façon autonome, doit avoir recours à un support respiratoire. Bien que la ventilation mécanique soit la thérapie traditionnellement appliquée aux blessés médullaires souffrant d’insuffisance respiratoire, les études ont démontré qu’elle pouvait contribuer à promouvoir une réponse inflammatoire ainsi que des dommages pulmonaires. L’interaction entre le traumatisme médullaire et la ventilation mécanique, indispensable au maintien de l’équilibre des échanges respiratoires, est inconnue à ce jour. En voulant protéger les tissus, cellules et organes, l’organisme met en œuvre toute une panoplie de réponses inflammatoires à différents endroits. Nous pensons que ces réponses peuvent être altérées via l’interaction entre ce traumatisme et cette ventilation mécanique, sous l’influence de la principale source cellulaire de cytokines pour la défense de l’hôte, le macrophage, récemment classé en deux phénotypes principaux: 1) l’activation classique de type M1 et 2) l’activation alternative de type M2. Le phénotype M1 est conduit par le facteur GM-CSF et induit par l’interféron IFN-ɣ ainsi que le lipopolysaccharide. Le phénotype M2 quant à lui, est conduit par le facteur M-CSF et induit par les interleukines IL-4, IL-13 ou IL-21. M1 relâche principalement IL-1β, IL-6, TNF-α et MIP-1α tandis que M2 principalement IL-10 et MCP-1. Toutefois, nous ignorons actuellement par quel type d’activation se manifestera cette réponse immunitaire et si l’application de support respiratoire pourrait entraîner un risque inflammatoire additionnel au site du traumatisme. Nous ignorons également si la ventilation mécanique affecterait, à distance, les tissus de la moelle épinière via une inflammation systémique et amplifierait alors le dommage initial. Il n’existe pas à ce jour, de thérapie qui ait montré d’effet bénéfique réel envers une récupération fonctionnelle des patients blessés médullaires. Il paraît donc essentiel de déterminer si la ventilation mécanique peut moduler l’inflammation post-traumatique à la fois au niveau pulmonaire et au site de la lésion. Ce travail visait à caractériser les liens entre l’inflammation issue du traumatisme médullaire et celle issue de la ventilation, dans le but de fournir une meilleure compréhension des mécanismes inflammatoires activés dans ce contexte. L’étude a été menée sur un modèle animal. Elle consistait à évaluer : 1) si le traumatisme médullaire influençait les réponses inflammatoires pulmonaires induites par la ventilation mécanique, y compris le phénotype des macrophages alvéolaires et 2) si la ventilation pouvait altérer à distance, les tissus de la moelle épinière. L’impact de la blessure médullaire sur l’inflammation pulmonaire et locale, induite par la ventilation fut interprété grâce à l’analyse des cellules inflammatoires dans les lavages broncho-alvéolaires et dans les tissus prélevés à l’endroit de la blessure après 24 heures. Ces analyses ont démontré un profil spécifique des cytokines pulmonaires et médullaires. Elles ont révélé que la ventilation mécanique a engendré un environnement pro-inflammatoire en faveur d’un phénotype M1 chez les animaux ayant bénéficié de la thérapie respiratoire. Inversement, l’atteinte thoracique chez les animaux sans ventilation, a montré qu’une réponse immunitaire avait été activée en faveur d’un environnement anti-inflammatoire de phénotype M2. La lésion cervicale quant à elle a induit un profil de cytokines différent et les réponses au stress oxydatif dans le poumon induites par la ventilation ont été réduites significativement. De plus, une lésion médullaire a augmenté l’expression d’IL-6 et la ventilation a diminué l’IL-1β et augmenté le TNF-α dans les tissus de la moelle. Finalement, ces données ont fourni les premières évidences que la ventilation a induit d’avantage à un phénotype pulmonaire M1 et que le traumatisme médullaire a impacté spécifiquement les réponses inflammatoires et oxydatives dans le poumon. La ventilation a contribué non seulement à distance à une inflammation des tissus médullaires lésés mais aussi des tissus sains.

Adaptive business intelligence for an open negotiation environment

Engineering of negotiation model allows to develop effective heuristic for business intelligence. Digital ecosystems demand open negotiation models. To define in advance effective heuristics is not compliant with the requirement of openness. The new challenge is to develop business intelligence in advance exploiting an adaptive approach. The idea is to learn business strategy once new negotiation model rise in the e-market arena. In this paper we present how recommendation technology may be deployed in an open negotiation environment where the interaction protocol models are not known in advance. The solution we propose is delivered as part of the ONE Platform, open source software that implements a fully distributed open environment for business negotiation