Predictors of substance use reduction in an epidemiological first-episode psychosis cohort.

AIM: To assess the predictors of a significant decrease or cessation of substance use (SU) in a treated epidemiological cohort of first-episode psychosis (FEP) patients. METHOD: Participants were FEP patients of the Early Psychosis Prevention and Intervention Centre in Australia. Patients' medical files were reviewed using a standardized file audit. Data on 432 patients with FEP and baseline co-morbid substance use disorder (SUD) were available for analysis. Predictors of reduction/cessation of SU at follow up were examined using logistic regression analyses. RESULTS: In univariate analyses, a reduction/cessation of SU was predicted by baseline measures reflecting higher education, employment, accommodation with others, cannabis use disorder (CUD) only (rather than poly-SUDs), better global functioning and better premorbid social and occupational functioning, later age at onset of psychosis, and a diagnosis of non-affective psychosis. In multivariate analysis, CUD alone and better premorbid social and occupational functioning remained significant predictors. CONCLUSIONS: Addressing SUDs and social and occupational goals in people with FEP may offer opportunities to prevent SUDs becoming more severe or entrenched. Further longitudinal research on recovery from SU and FEP is needed to disentangle directions of influence and identify key targets for intervention.

Neurocognitive deficits and personality traits among euthymic patients with mood disorders in late life.

BACKGROUND: Previous studies revealed that acute depressive episodes are associated with both cognitive deficits and modified personality patterns in late life. Whether or not these psychological changes are present after remission remains a matter of debate. To date, no study provided concomitant assessment of cognition and psychological functions in this particular clinical setting. METHOD: Using a cross-sectional design, 58 remitted outpatients (36 with unipolar early-onset depression (EOD) and 22 with bipolar disorder (BD)) were compared to 62 healthy controls. Assessment included detailed neurocognitive measures and evaluation of the five factor personality dimensions (NEO-Personality Inventory). RESULTS: Group comparisons revealed significant slower processing speed, working and episodic memory performances in BD patients. EOD patients showed cognitive abilities comparable to those of elderly controls. In NEO PI assessment, both BD and EOD patients displayed higher Depressiveness facet scores. In addition, the EOD but not BD group had lower Extraversion factor, and Warmth and Positive Emotion facet scores than controls. CONCLUSIONS: After remission from acute affective symptoms, older BD patients show significant impairment in several cognitive functions while neuropsychological performances remained intact in elderly patients with EOD. Supporting a long-lasting psychological vulnerability, EOD patients are more prone to develop emotion-related personality trait changes than BD patients.

Emotions in a Web-based Learning Environment

The aim of this thesis was to examine emotions in a web-based learning environment (WBLE). Theoretically, the thesis was grounded on the dimensional model of emotions. Four empirical studies were conducted. Study I focused on students’ anxiety and their self-efficacy in computer-using situations. Studies II and III examined the influence of experienced emotions on students’ collaborative visible and non-collaborative invisible activities and lurking in a WBLE. Study II also focused on the antecedents of the emotions students experience in a web-based learning environment. Study IV concentrated on clarifying the differences between emotions experienced in face-to-face and web-based collaborative learning. The results of these studies are reported in four original research articles published in scientific journals. The present studies demonstrate that emotions are important determinants of student behaviour in a web-based learning, and justify the conclusion that interactions on the web can and do have an emotional content. Based on the results of these empirical studies, it can be concluded that the emotions students experience during the web-based learning result mostly from the social interactions rather than from the technological context. The studies indicate that the technology itself is not the only antecedent of students’ emotional reactions in the collaborative web-based learning situations. However, the technology itself also exerted an influence on students’ behaviour. It was found that students’ computer anxiety was associated with their negative expectations of the consequences of using technology-based learning environments in their studies. Moreover, the results also indicated that student behaviours in a WBLE can be divided into three partially overlapping classes: i) collaborative visible ii) non-collaborative invisible activities, and iii) lurking. What is more, students’ emotions experienced during the web-based learning affected how actively they participated in such activities in the environment. Especially lurkers, i.e. students who seldom participated in discussions but frequently visited the online environment, experienced more negatively valenced emotions during the courses than did the other students. This result indicates that such negatively toned emotional experiences can make the lurking individuals less eager to participate in other WBLE courses in the future. Therefore, future research should also focus more precisely on the reasons that cause individuals to lurk in online learning groups, and the development of learning tasks that do not encourage or permit lurking or inactivity. Finally, the results from the study comparing emotional reactions in web-based and face-to-face collaborative learning indicated that the learning by means of web-based communication resulted in more affective reactivity when compared to learning in a face-to-face situation. The results imply that the students in the web-based learning group experienced more intense emotions than the students in the face-to-face learning group.The interpretations of this result are that the lack of means for expressing emotional reactions and perceiving others’ emotions increased the affectivity in the web-based learning groups. Such increased affective reactivity could, for example, debilitate individual’s learning performance, especially in complex learning tasks. Therefore, it is recommended that in the future more studies should be focused on the possibilities to express emotions in a text-based web environment to ensure better means for communicating emotions, and subsequently, possibly decrease the high level of affectivity. However, we do not yet know whether the use of means for communicating emotional expressions via the web (for example, “smileys” or “emoticons”) would be beneficial or disadvantageous in formal learning situations. Therefore, future studies should also focus on assessing how the use of such symbols as a means for expressing emotions in a text-based web environment would affect students’ and teachers’ behaviour and emotional state in web-based learning environments.

Quality of web-based information on bipolar disorder

OBJECTIVE: To evaluate web-based information on bipolar disorder and to assess particular content quality indicators. METHODS: Two keywords, "bipolar disorder" and "manic depressive illness" were entered into popular World Wide Web search engines. Websites were assessed with a standardized proforma designed to rate sites on the basis of accountability, presentation, interactivity, readability and content quality. "Health on the Net" (HON) quality label, and DISCERN scale scores were used to verify their efficiency as quality indicators. RESULTS: Of the 80 websites identified, 34 were included. Based on outcome measures, the content quality of the sites turned-out to be good. Content quality of web sites dealing with bipolar disorder is significantly explained by readability, accountability and interactivity as well as a global score. CONCLUSIONS: The overall content quality of the studied bipolar disorder websites is good.

Perceptual defense in anxiety disorders

RÉSUMÉ Plusieurs auteurs ont étudié la perception en fonction de la psychopathologie. Dans cette optique, Borgeat, David, Saucier et Dumont en 1994 et Borgeat, Sauvageau, David et Saucier en 1997 ont utilisé la méthode tachistoscopique afin de comparer, dans une étude prospective, la perception de stimuli émotionnels entre des femmes souffrant d'une dépression du post- partum et des femmes non atteintes. Par ailleurs, des études antérieures, notamment les travaux de MacLeod et Rutherford en 1992, avaient montré la possibilité d'un processus de perception différent entre sujets anxieux et non anxieux. L'étude actuelle pose l'hypothèse d'une interaction entre caractéristiques du stimulus et trouble anxieux du sujet. Cette hypothèse suppose donc un processus préconscient de l'information, avec analyse sémantique de cette dernière, à même d'influencer (inhiber ou faciliter) la perception de certains stimuli en fonction de leur charge affective. L'étude que nous présentons a pour but d'évaluer la perception de stimuli anxiogènes chez les patients atteints de troubles anxieux, et plus particulièrement chez des sujets souffrant d'attaque de panique et de troubles obsessionnels-compulsifs. A cette fin, nous avons choisi, contrairement à la plupart des études effectuées jusqu'à présent où la méthode Stroop avait été utilisée, la technique tachistoscopique qui, à notre avis, permet une mesure plus directe de la rapidité du processus perceptuel. Ainsi, trois groupes de sujets ont pris part à l'étude : un groupe contrôle (N = 22), un groupe de patients souffrant d'attaques de panique (N = 21) et un groupe de patients atteints de troubles obsessionnels-compulsifs (N = 20). Ces 63 sujets, âgés entre 18 et 60 ans, ont à la fois répondu au Fear Questionnaire ainsi qu'au Questionnaire Beck 13 pour la dépression et procédé à la reconnaissance de 42 mots (six groupes de sept mots) présentés aléatoirement à l'ordinateur, en cycles successifs de 15 millisecondes. Cinq parmi les six groupes de mots se référaient à un trouble anxieux spécifique, le sixième étant considéré comme un groupe de mots « neutres ». Le temps, en millisecondes, nécessaire à la reconnaissance de chaque mot a été enregistré. Les résultats montrent une lenteur de la part des patients souffrant d'attaques de panique pour la reconnaissance de tous les stimuli par rapport aux sujets contrôle, avec une performance intermédiaire entre les deux groupes pour les patients atteints de troubles obsessionnels-compulsifs. De plus, l'analyse statistique a révélé deux effets d'interaction : les patients atteints d'attaques de panique sont plus rapides à reconnaître le groupe de mots en rapport avec leur angoisse, de même que les patients soufflant de troubles obsessionnels- compulsifs ont un temps moyen de reconnaissance des mots en rapport avec leur trouble plus bas que prévu. Ces résultats amènent à une double conclusion. La première est que les patients anxieux manifestent une défense perceptuelle globale face aux stimuli anxiogènes en général, et que cette défense est plus marquée chez les patients atteints d'attaques de panique que chez les sujets souffrant de troubles obsessionnels-compulsifs. La deuxième est que ces mêmes patients, confrontés à des stimuli en rapport avec leur propre angoisse, montrent une vigilance accrue. Ainsi, ces données évoquent une double stratégie de traitement de l'information chez les patients anxieux : un évitement perceptuel général face à l'information émotionnellement chargée, et un traitement sélectif de l'information ayant un rapport direct avec l'angoisse dont ils soufflent. SUMMARY Prior research by MacLeod and Rutherford (1992) indicates that anxious subjects could have perceptual strategies different from nonanxious subjects. 42 verbal stimuli of six types (disease, social anxiety, panic, agoraphobia, obsessive-compulsive, and neutral) were tachistoscopically presented to three groups of subjects, aged 18 to 60 years: Panic Disorder group (n =21: 13 women and 8 men), and Obsessive-Compulsive Disorder group (n=20: 14 women and 6 men), recruited from an outpatient clinic, and a Control group (n=22: 14 women and 8 men), recruited among students and hospital staff. The times required for correct identification were generally longer for anxious subjects but quicker for stimuli specifically related to their disorder. The data could indicate a two-step perceptual strategy or two distinct ways of perceiving, usually, a generalized perceptual defense for a majority of anxiety-loaded stimuli, but also a selectively facilitated processing for stimuli specific to the disorder.

Validation of the spiritual distress assessment tool in older hospitalized patients.

ABSTRACT:¦BACKGROUND: The Spiritual Distress Assessment Tool (SDAT) is a 5-item instrument developed to assess unmet spiritual needs in hospitalized elderly patients and to determine the presence of spiritual distress. The objective of this study was to investigate the SDAT psychometric properties.¦METHODS: This cross-sectional study was performed in a Geriatric Rehabilitation Unit. Patients (N = 203), aged 65 years and over with Mini Mental State Exam score ≥ 20, were consecutively enrolled over a 6-month period. Data on health, functional, cognitive, affective and spiritual status were collected upon admission. Interviews using the SDAT (score from 0 to 15, higher scores indicating higher distress) were conducted by a trained chaplain. Factor analysis, measures of internal consistency (inter-item and item-to-total correlations, Cronbach α), and reliability (intra-rater and inter-rater) were performed. Criterion-related validity was assessed using the Functional Assessment of Chronic Illness Therapy-Spiritual well-being (FACIT-Sp) and the question "Are you at peace?" as criterion-standard. Concurrent and predictive validity were assessed using the Geriatric Depression Scale (GDS), occurrence of a family meeting, hospital length of stay (LOS) and destination at discharge.¦RESULTS: SDAT scores ranged from 1 to 11 (mean 5.6 ± 2.4). Overall, 65.0% (132/203) of the patients reported some spiritual distress on SDAT total score and 22.2% (45/203) reported at least one severe unmet spiritual need. A two-factor solution explained 60% of the variance. Inter-item correlations ranged from 0.11 to 0.41 (eight out of ten with P < 0.05). Item-to-total correlations ranged from 0.57 to 0.66 (all P < 0.001). Cronbach α was acceptable (0.60). Intra-rater and inter-rater reliabilities were high (Intraclass Correlation Coefficients ranging from 0.87 to 0.96). SDAT correlated significantly with the FACIT-Sp, "Are you at peace?", GDS (Rho -0.45, -0.33, and 0.43, respectively, all P < .001), and LOS (Rho 0.15, P = .03). Compared with patients showing no severely unmet spiritual need, patients with at least one severe unmet spiritual need had higher odds of occurrence of a family meeting (adjOR 4.7, 95%CI 1.4-16.3, P = .02) and were more often discharged to a nursing home (13.3% vs 3.8%; P = .027).¦CONCLUSIONS: SDAT has acceptable psychometrics properties and appears to be a valid and reliable instrument to assess spiritual distress in elderly hospitalized patients.

Neuropeptide Y and corticotropin-releasing hormone in CSF mark response to antidepressive treatment with citalopram.

Neuropeptides appear to play a role in the pathophysiology of depression and electroconvulsive treatment and lithium affect these compounds in human cerebrospinal fluid (CSF) and rodent brain. Consequently, we investigated whether long-term treatment with the selective serotonin reuptake inhibitor (SSRI) citalopram (Cit) would also affect neuropeptides in CSF of depressed patients. Changes in CSF monoamine metabolites were also explored. CSF concentrations of corticotropin-releasing hormone (CRH)-like immunoreactivity (-LI), neuropeptide Y (NPY)-LI, and Cit were determined in 21 patients with major depression. Lumbar puncture was performed in the morning at baseline and was repeated after at least 4 wk of Cit treatment (40 mg/d). The severity of depression was assessed by the Hamilton Rating Scale for Depression (HAMD). Cit treatment was associated with a significant increase in NPY-LI and decrease in CRH-LI. An evaluation of the relationship between changes in concentrations of NPY-LI, CRH-LI, and the clinical response showed significant correlations between these parameters. Significant NPY and CRH changes in CSF following treatment as well as correlations to changes in HAMD support the hypothesis that these two peptides play a role in affective disorders and are markers of therapeutic response.

Multimodal MRI analysis of structural and functional networks in the human brain : application to two clinical studies : driving abilities under THC intoxication and early white matter changes in FXTAS

Les approches multimodales dans l'imagerie cérébrale non invasive sont de plus en plus considérées comme un outil indispensable pour la compréhension des différents aspects de la structure et de la fonction cérébrale. Grâce aux progrès des techniques d'acquisition des images de Resonance Magnetique et aux nouveaux outils pour le traitement des données, il est désormais possible de mesurer plusieurs paramètres sensibles aux différentes caractéristiques des tissues cérébraux. Ces progrès permettent, par exemple, d'étudier les substrats anatomiques qui sont à la base des processus cognitifs ou de discerner au niveau purement structurel les phénomènes dégénératifs et développementaux. Cette thèse met en évidence l'importance de l'utilisation d'une approche multimodale pour étudier les différents aspects de la dynamique cérébrale grâce à l'application de cette approche à deux études cliniques: l'évaluation structurelle et fonctionnelle des effets aigus du cannabis fumé chez des consommateurs réguliers et occasionnels, et l'évaluation de l'intégrité de la substance grise et blanche chez des jeunes porteurs de la prémutations du gène FMR1 à risque de développer le FXTAS (Fragile-X Tremor Ataxia Syndrome). Nous avons montré que chez les fumeurs occasionnels de cannabis, même à faible concentration du principal composant psychoactif (THC) dans le sang, la performance lors d'une tâche visuo-motrice est fortement diminuée, et qu'il y a des changements dans l'activité des trois réseaux cérébraux impliqués dans les processus cognitifs: le réseau de saillance, le réseau du contrôle exécutif, et le réseau actif par défaut (Default Mode). Les sujets ne sont pas en mesure de saisir les saillances dans l'environnement et de focaliser leur attention sur la tâche. L'augmentation de la réponse hémodynamique dans le cortex cingulaire antérieur suggère une augmentation de l'activité introspective. Une investigation des ef¬fets au niveau cérébral d'une exposition prolongée au cannabis, montre des changements persistants de la substance grise dans les régions associées à la mémoire et au traitement des émotions. Le niveau d'atrophie dans ces structures corrèle avec la consommation de cannabis au cours des trois mois précédant l'étude. Dans la deuxième étude, nous démontrons des altérations structurelles des décennies avant l'apparition du syndrome FXTAS chez des sujets jeunes, asymptomatiques, et porteurs de la prémutation du gène FMR1. Les modifications trouvées peuvent être liées à deux mécanismes différents. Les altérations dans le réseau moteur du cervelet et dans la fimbria de l'hippocampe, suggèrent un effet développemental de la prémutation. Elles incluent aussi une atrophie de la substance grise du lobule VI du cervelet et l'altération des propriétés tissulaires de la substance blanche des projections afférentes correspondantes aux pédoncules cérébelleux moyens. Les lésions diffuses de la substance blanche cérébrale peu¬vent être un marquer précoce du développement de la maladie, car elles sont liées à un phénomène dégénératif qui précède l'apparition des symptômes du FXTAS. - Multimodal brain imaging is becoming a leading tool for understanding different aspects of brain structure and function. Thanks to the advances in Magnetic Resonance imaging (MRI) acquisition schemes and data processing techniques, it is now possible to measure different parameters sensitive to different tissue characteristics. This allows for example to investigate anatomical substrates underlying cognitive processing, or to disentangle, at a pure structural level degeneration and developmental processes. This thesis highlights the importance of using a multimodal approach for investigating different aspects of brain dynamics by applying this approach to two clinical studies: functional and structural assessment of the acute effects of cannabis smoking in regular and occasional users, and grey and white matter assessment in young FMR1 premutation carriers at risk of developing FXTAS. We demonstrate that in occasional smokers cannabis smoking, even at low concentration of the main psychoactive component (THC) in the blood, strongly decrease subjects' performance on a visuo-motor tracking task, and globally alters the activity of the three brain networks involved in cognitive processing: the Salience, the Control Executive, and the Default Mode networks. Subjects are unable to capture saliences in the environment and to orient attention to the task; the increase in Hemodynamic Response in the Anterior Cingulate Cortex suggests an increase in self-oriented mental activity. A further investigation on long term exposure to cannabis, shows a persistent grey matter modification in brain regions associated with memory and affective processing. The degree of atrophy in these structures also correlates with the estimation of drug use in the three months prior the participation to the study. In the second study we demonstrate structural changes in young asymptomatic premutation carriers decades before the onset of FXTAS that might be related to two different mechanisms. Alteration of the cerebellar motor network and of the hippocampal fimbria/ fornix, may reflect a potential neurodevelopmental effect of the premutation. These include grey matter atrophy in lobule VI and modification of white matter tissue property in the corresponding afferent projections through the Middle Cerebellar Peduncles. Diffuse hemispheric white matter lesions that seem to appear closer to the onset of FXTAS and be related to a neurodegenerative phenomenon may mark the imminent onset of FXTAS.

Intercultural Competence of Masters of Science in Business Administration and in Technology

Tutkielman tavoitteena on selvittää minkälaista kulttuurienvälistä kompetenssia Lappeenrannan teknillisestä yliopistosta vastavalmistuneilla kauppatieteenmaistereilla sekä diplomi-insinööreillä tulisi olla työnantajien näkökulmasta. Tutkimuksen tarkoituksena on myös tarkastella, että voidaanko kaikkia Lappeenrannan teknillisestä yliopistosta valmistuvia kutsua Kansainvälisiksi Huippuosaajiksi sekä kuinka Lappeenrannan teknillinen yliopisto voisi parantaa vastavalmistuvien kulttuurienvälistä kompetenssia. Teoreettinen osa tarkastelee kulttuurienvälisen kommunikaation tärkeimpiä elementtejä, kulttuurienvälistä kompetenssia ja vastavalmistuneiden kauppatieteenmaistereiden sekä diplomi-insinöörien tarvitsemaa ammatillista osaamista. Empiria koostuu kymmenen työnantajien teemahaastattelun tuloksista. Lopuksi johtopäätöksissä empirian tuloksia verrataan teorian löydöksiin. Tulokset osoittavat että kulttuurienvälinen kompetenssi koostuu kolmesta dimensiosta: henkilökohtaisista ominaisuuksista, tiedosta ja kommunikointikyvystä. Henkilökohtaisiin ominaisuuksiin sisältyvät empaattisuus, epävarmuuden sietokyky sekä avoin ja utelias asenne. Tieto - ulottuvuus koostuu yleisestä ja erityisestä kulttuuritiedosta, kielitaidosta sekä ammatillisesta osaamisesta. Kommunikointikykyyn puolestaan sisältyvät hyvät vuorovaikutustaidot. Työnantajat olettavat nykyään vastavalmistuneilla olevan ammatillisen osaamisen ja kielitaidon lisäksi, kulttuuritietoutta sekä kansainvälistä kokemusta. Lappeenrannan teknillinen yliopisto voisi parantaa vastavalmistuneiden kulttuurienvälistä kompetenssia tarjoamalla kulttuurienvälisen kommunikaation opetusta.

Dysregulated activation of the CXCR4/CXCL12 Axisand its role in the malignant phenotype of neural crest-derived neuroblastoma tumours

Résumé: Le neuroblastome (NB) est un néoplasme dévastateur de la petite enfance, pour lequel il n'existe pas encore de traitement efficace. Les chimiokines et leurs récepteurs ont été impliqués dans la croissance des tumeurs et la formation de métastases, et en particulier, il a été rapporté que l'axe CXCR4/CXCL12 dirigeait le guidage, ainsi que l'invasion des cellules cancéreuses vers des organes spécifiques. Notre étude avait pour objectif d'analyser le rôle de CxCR4 exogène dans le comportement malin du NB, en étudiant la croissance des cellules tumorales, leur capacité de survie, de migration et d'invasion in vitro et en validant ces résultats grâce à un modèle orthotopique murin de la progression tumorale du NB in vivo. La surexpression de CXCR4 dans les cellules faiblement métastatiques IGR-NB8 n'exprimant pas CXCR4, a augmenté la mobilité des cellules vers CXCL12 in vitro. De plus, les cellules surexprimant CXCR4 ont été moins affectées par la privation de sérum que les cellules contrôles. Le volume des tumeurs chez les animaux greffés de manière orthotopique avec les cellules NB8-CXCR4-C3 était significativement plus élevé que celui des tumeurs issues des cellules contrôles NB8-E6 au moment du sacrifice des animaux. Cependant, aucune induction des métastases n'a été observée. La lignée cellulaire IGR-N91, aux propriétés invasives et métastatiques in vivo, exprime constitutivement des quantités modérées de CXCR4. La surexpression du récepteur dans cette lignée a accéléré la croissance tumorale in vivo, mais n'a pas augmenté pas l'occurrence des métastases. Les cellules IGR-N91, dans lesquelles l'expression de CXCR4 a été éteinte, suite à l'introduction de shRNA stable contre CXCR4, a présenté une croissance cellulaire plus lente, in vitro et in vivo. Afin d'identifier les gènes et les voies de signalisation impliqués dans les effets dépendants de CXCR4-CXCL12 dans le NB, des analyses du profil d'expression des gènes ont été effectuées sur les lignées cellulaires transfectées ou non (contrôle). Trois clones contrôles ont été comparés à 3 clones surexprimant CXCR4 pour chacune des lignées (IGR-NB8 et IGR-N91). Les analyses biostatiques ont identifié 10 gènes induits, dont CXCR4, et 31 gènes réprimés, communs entre tous les clones surexprimant CXCR4. Ces observations démontrent que la surexpression de CXCR4 dans le NB stimule la croissance, la survie et la migration chémotactique des cellules tumorales, mais est insuffisante pour induire ou augmenter leurs capacités invasives et métastatiques. Les voies de signalisation activées suite à la surexpression de CXCR4 et identifiées à travers le profil global de l'expression des gènes pourraient être des cibles intéressantes pour le développement de drogues capables d'inhiber la croissance tumorale. Abstact: Neuroblastoma (NB) is a devastating childhood neoplasm for which there is not yet an efficient treatment. Chemokines and their receptors have been involved in tumour growth and metastasis, and in particular the CXCR4/CXCL12 axis has been reported to mediate organ-specific cancer cells homing and invasion. The purpose of the study was to investigate the role of ectopic CXCR4 in the malignant behaviour of NB by studying tumour cell growth, survival, migration, and invasion in vitro and by validating these results using a murine orthotopic model of NB tumour progression in vivo. CXCR4 overexpression in the low metastatic, CXCR4-negative IGR-NB8 cells resulted in CXCL12-mediated chemotaxis in vitro. Furthermore, CXCR4 overexpressing cells were less affected by serum deprivation than mock-transduced cells. In vivo studies revealed that, at sacrifice, volumes of tumours developing in mice with orthotopically implanted NB8-CXCR4-C3 cells, were significantly increased compared to NB8-E6 control tumours. However, no induction of metastases was observed. The in vivo invasive and metastatic cell line IGR-N91 cell line constitutively expresses moderate levels of CXCR4. Overexpression of CXCR4 enhanced in vivo tumour growth but did not increase the occurrence of metastases. IGR-N91 cells where CXCR4 has been knocked-down by stable shRNA grew slower in vitro and in vivo. To identify genes and pathways involved in the CXCR4/CXCL12-mediated effects in NB expression, profiles analyses (Affymetrix) were performed on transduced and control cell lines. Three mock-transduced clones were compared to three CXCR4 overexpressing clones of either cell line IGR-NB8 and IGR-N91. Biostatistical analysis identified 10 commonly upregulated genes (including CXCR4) and 31 downregulated genes common to all CXCR4 overexpressing clones. These observations demonstrate that overexpression of CXCR4 in NB stimulates tumour cell growth, survival, and chemotactic migration but is not sufficient to induce or enhance invasive and metastatic capacities. Activated pathways upon CXCR4 overexpression, identified through global gene expression profiling may be interesting targets for drugs inhibiting tumour growth.

Evaluación de la educación emocional en el ciclo medio de Educación Primaria

El principal propósito de la educación consiste en favorecer el desarrollo integral de la persona, lo cual implica atender el aspecto cognitivo y afectivo. Tradicionalmente, se han priorizado sólo los contenidos cognitivos por este motivo queremos incidir sobre los afectos. El objetivo general de este trabajo de investigación que presentamos consiste en aplicar y evaluar un Programa de Educación Emocional (PEEP), integrado dentro del currículum de Primaria de ciclo medio que ayude a prevenir los efectos nocivos de las emociones negativas y facilite la relación consigo mismo y con los demás. Objetivo general que se constatara a partir de cuatro criterios: conseguir un mejor conocimiento de las propias emociones y de las emociones de los demás, desarrollar estrategias de regulación emocional, mejorar la autoestima, aprender habilidades de vida y socioemocionales. Pues, la finalidad es intervenir en la mejora de la educación emocional de los alumnos entre los 8 y los 10 años, en total 510 alumnos de los cuales 104 formaron la muestra de investigación. Fueron divididos en dos grupos el grupo experimental y el grupo control, ambos constituían una muestra homogénea y estadísticamente comparable por lo que podíamos plantearnos una intervención y valorar su incidencia. Los resultados indican que mejora el nivel de Educación Emocional (EE) de estos alumnos con un nivel de significación de p= 0,001. A partir de este momento, podemos concretar que los resultados conseguidos por los alumnos que han seguido la aplicación del programa mejoran significativamente. Este resultado, nos permite afirmar que el uso intencional del programa de educación emocional para mejorar el ámbito afectivo ha incidido positivamente en el proceso de aprendizaje de los alumnos. Sin embargo consideramos esencial llevar a cabo una formación y posterior evaluación del profesorado en EE, como paso previo necesario para una aplicación óptima del programa.

Scaffolding through the network: analysing the promotion of improved online scaffolds among university students

This article explores how to enrich scaffolding processes among university students using specific Computer Supported Collaborative Learning –CSCL- software. A longitudinal case study was designed, in which eighteen students participated in a twelve-month learning project. During this period the students followed an instructional process, using the CSCL software to support and improve the students’ interaction processes, in particular the processes of giving and receiving assistance. Our research analyzed the evolution of the quality of the students’ interaction processes and the students’ learning results. The effects of the students’ participation in the CSCL environment have been described in terms of their development of affective, cognitive and metacognitive learning processes. Our results showed that the specific activities that students performed while working with the CSCL system triggered specific learning processes, which had a positive incidence on their learning results.

The Impact of a Character Posture Model on the Communication of Affect in an Immersive Virtual Environment

This paper presents the quantitative and qualitative findings from an experiment designed to evaluate a developing model of affective postures for full-body virtual characters in immersive virtual environments (IVEs). Forty-nine participants were each requested to explore a virtual environment by asking two virtual characters for instructions. The participants used a CAVE-like system to explore the environment. Participant responses and their impression of the virtual characters were evaluated through a wide variety of both quantitative and qualitative methods. Combining a controlled experimental approach with various data-collection methods provided a number of advantages such as providing a reason to the quantitative results. The quantitative results indicate that posture plays an important role in the communication of affect by virtual characters. The qualitative findings indicated that participants attribute a variety of psychological states to the behavioral cues displayed by virtual characters. In addition, participants tended to interpret the social context portrayed by the virtual characters in a holistic manner. This suggests that one aspect of the virtual scene colors the perception of the whole social context portrayed by the virtual characters. We conclude by discussing the importance of designing holistically congruent virtual characters especially in immersive settings.

Aspirin and statin use and the subsequent development of depression in men and women: Results from a longitudinal population-based study.

OBJECTIVE: Low-grade chronic inflammation is one potential mechanism underlying the well-established association between major depressive disorder (MDD) and increased cardiovascular morbidity. Both aspirin and statins have anti-inflammatory properties, which may contribute to their preventive effect on cardiovascular diseases. Previous studies on the potentially preventive effect of these drugs on depression have provided inconsistent results. The aim of the present paper was to assess the prospective association between regular aspirin or statin use and the incidence of MDD. METHOD: This prospective cohort study included 1631 subjects (43.6% women, mean age 51.7 years), randomly selected from the general population of an urban area. Subjects underwent a thorough physical evaluation as well as semi-structured interviews investigating DSM-IV mental disorders at baseline and follow-up (mean duration 5.2 years). Analyses were adjusted for a wide array of potential confounders. RESULTS: Our main finding was that regular aspirin or statin use at baseline did not reduce the incidence of MDD during follow-up, regardless of sex or age (hazard ratios, aspirin: 1.19; 95%CI, 0.68-2.08; and statins: 1.25; 95%CI, 0.73-2.14; respectively). LIMITATIONS: Our study is not a randomized clinical trial and could not adjust for all potential confounding factors, information on aspirin or statin use was collected only for the 6 months prior to the evaluations, and the sample was restricted to subjects between 35 and 66 years of age. CONCLUSION: Our data do not support a large scale preventive treatment of depression using aspirin or statins in subjects aged from 35 to 66 years from the community.

Targeted inactivation of hypocretin receptors in dopaminergic and noradrenergic systems alters brain activity in wakefulness

Since the discovery of hypocretins/orexins (Hcrt/Ox) in 1998, several narcoleptic mouse models, such as Hcrt-KO, Hcrtrl-KO, Hcrtr2-KO and double receptors KO mice, and orexin-ataxin transgenic mice were generated. The available Hcrt mouse models do not allow the dissection of the specific role of Hcrt in each target region. Dr. Anne Vassalli generated loxP-flanked alleles for each Hcrt receptor, which are manipulated by Cre recombinase to generate mouse lines with disrupted Hcrtrl or Hcrtr2 (or both) in cell type-specific manner. The role of noradrenaline (NA) and dopamine (OA) in ttie regulation of vigilance states is well documented. The purpose of this thesis is to explore the role of the Hcrt input into these two monoaminergic systems. Chronic loss of Hcrtrl in NA neurons consolidated paradoxical sleep (PS), and altered wakefulness brain activity in baseline, during the sleep deprivation (SD), and when mice were challenged by a novel environment, or exposed to nest-building material. The analysis of alterations in the sleep EEG delta power showed a consistent correlation with the changes in the preceding waking quality in these mice. Targeted inactivation of Hcrt input into DA neurons showed that Hcrtr2 inactivation present the strongest phenotype. The loss of Hcrtr2 in DA neurons caused modified brain activities in spontaneous wakefulness, during SD, and in novel environmental conditions. In addition to alteration of wakefulness quality and quantity, conditional inactivation of Hcrtr2 in DA neurons caused an increased in time spent in PS in baseline and a delayed and less complete PS recovery after SD. In the first 30 min of sleep recovery, single (i.e. for Hcrtrl or Hcrtr2) conditional knockout receptor mice had opposite changes in delta activity, including an increased power density in the fast delta range with specific inactivation of Hcrtr2, but a decreased power density in the same range with specific inactivation of Hcrtrl in DA cells. These studies demonstrate a complex impact of Hcrt receptors signaling in both NA and DA system, not only on quantity and quality of wakefulness, but also on PS amount regulation as well as on SWS delta power expression. -- Depuis la découverte des hypocrétines/orexines (Hcrt/Ox) en 1998, plusieurs modèles de souris, narcoleptiques telles que Hcrt-KO, Hcrtr2-KO et récepteurs doubles KO et les souris transgéniques orexine-ataxine ont été générés. Les modèles de souris Hcrt disponibles ne permettaient pas la dissection du rôle spécifique de l'Hcrt dans chaque noyau neuronal cible. Notre laboratoire a généré des allèles loxP pour chacun des 2 gènes codant pour les récepteurs Hcrtr, qui sont manipulés par recombinase Cre pour générer des lignées de souris avec Hcrtrl inactivé, ou Hcrtr2 inactivé, (ou les deux), spécifiquement dans un type cellulaire particulier. Le rôle de la noradrénaline (NA) et la dopamine (DA) dans la régulation des états de vigilance est bien documentée. Le but de cette thèse est d'étudier le rôle de l'afférence Hcrt dans ces deux systèmes monoaminergiques au niveau de l'activité cérébrale telle qu'elle apparaît dans l'électroencéphalogramme (EEG). Mon travail montre que la perte chronique de Hcrtrl dans les neurones NA consolide le sommeil paradoxal (PS), et l'activité cérébrale de l'éveil est modifiée en condition spontanée, au cours d'une experience de privation de sommeil (SD), et lorsque les souris sont présentées à un nouvel environnement, ou exposées à des matériaux de construction du nid. Ces modifications de l'éveil sont corrélées à des modifications de puissance de l'activité delta du sommeil lent qui le suit. L'inactivation ciblée des Hcrtrs dans les neurones DA a montré que l'inactivation Hcrtr2 conduit au phénotype le plus marqué. La perte de Hcrtr2 dans les neurones DA mène à des modification d'activité cérébrale en éveil spontané, pendant SD, ainsi que dans des conditions environnementales nouvelles. En plus de l'altération de la qualité de l'éveil et de la quantité, l'inactivation conditionnelle de Hcrtr2 dans les neurones DA a provoqué une augmentation du temps passé en sommeil paradoxal (PS) en condition de base, et une reprise retardée et moins complète du PS après SD. Dans les 30 premières minutes de la récupération de sommeil, les modèles inactivés pour un seul des récepteurs (ie pour Hcrtrl ou Hcrtr2 seulement) montrent des changements opposés en activité delta, en particulier une densité de puissance accrue dans le delta rapide avec l'inactivation spécifique de Hcrtr2, mais une densité de puissance diminuée dans cette même gamme chez les souris inactivées spécifiquement en Hcrtrl dans les neurones DA. Ces études démontrent un impact complexe de l'inactivation de la neurotransmission au niveau des récepteurs d'Hcrt dans les deux compartiments NA et DA, non seulement sur la quantité et la qualité de l'éveil, mais aussi sur la régulation de quantité de sommeil paradoxal, ainsi que sur l'expression de la puissance delta pendant le sommeil lent.