Value / personality - attitude - behavior hierarchy and its impact on individual performance in the context of market orientation

The purpose of this dissertation is to better understand how individual employees? values and personality traits influence their attitudes toward market orientation; how such attitudes impact their market-oriented behaviors; and how in turn, these behaviors lead to their superior individual performance. To investigate these relationships, an empirical study was conducted in the French speaking part of Switzerland and data were collected from a sample of service firms? employees from diverse departments and hierarchical levels. To a large extent, the results support the hypothesis of a hierarchical chain moving from value / personality to attitude to behavior to individual performance in relation to market orientation. Le sujet de cette thèse de doctorat est de mieux comprendre comment les valeurs et les traits de personnalité des employés influencent leurs attitudes envers l'orientation vers le marché ; comment ces attitudes ont un effet sur les comportements orientés vers le marché de ces employés et enfin, comment ces comportements conduisent à une meilleure performance individuelle. Afin d'étudier ces relations, une enquête a été conduite en Suisse romande et des données ont été collectées auprès d'un échantillon d'employés d'entreprises de service de différents départements et niveaux hiérarchiques. Les résultats sont concordants avec l'hypothèse d'une chaîne causale allant des valeurs / traits de personnalité aux attitudes, aux comportements et finalement à la performance individuelle dans le contexte de l'orientation vers le marché.

Structure-function relationships of the alpha1b-adrenergic receptor.

The alpha1b-adrenergic receptor (AR) is a member of the large superfamily of seven transmembrane domain (TMD) G protein-coupled receptors (GPCR). Combining site-directed mutagenesis of the alpha1b-AR with computational simulations of receptor dynamics, we have explored the conformational changes underlying the process of receptor activation, i.e. the transition between the inactive and active states. Our findings suggest that the structural constraint stabilizing the alpha1b-AR in the inactive form is a network of H-bonding interactions amongst conserved residues forming a polar pocket and R143 of the DRY sequence at the end of TMDIII. We have recently reported that point mutations of D142, of the DRY sequence and of A293 in the distal portion of the third intracellular loop resulted in ligand-independent (constitutive) activation of the alpha1b-AR. These constitutively activating mutations could induce perturbations resulting in the shift of R143 out of the polar pocket. The main role of R143 may be to mediate receptor activation by triggering the exposure of several basic amino acids of the intracellular loops towards the G protein. Our investigation has been extended also to the biochemical events involved in the desensitization process of alpha1b-AR. Our results indicate that immediately following agonist-induced activation, the alpha1b-AR can undergo rapid agonist-induced phosphorylation and desensitization. Different members of the G protein coupled receptor kinase family can play a role in agonist-induced regulation of the alpha1b-AR. In addition, constitutively active alpha1b-AR mutants display different phosphorylation and internalization features. The future goal is to further elucidate the molecular mechanism underlying the complex equilibrium between activation and inactivation of the alpha1b-AR and its regulation by pharmacological substances. These findings can help to elucidate the mechanism of action of various agents displaying properties of agonists or inverse agonists at the adrenergic system.

Family relationships and learning experiences in anxious vs. non-anxious families: Are there differences ?

L'objectif principal de ce travail était d'explorer les relations parent-enfant et les processus d'apprentissage familiaux associés aux troubles anxieux. A cet effet, des familles ayant un membre anxieux (la mère ou l'enfant) ont été comparées avec des familles n'ayant aucun membre anxieux. Dans une première étude, l'observation de l'interaction mère-enfant, pendant une situation standardisée de jeu, a révélé que les mères présentant un trouble panique étaient plus susceptibles de se montrer verbalement contrôlantes, critiques et moins sensibles aux besoins de l'enfant, que les mères qui ne présentaient pas de trouble panique. Une deuxième étude a examiné les perceptions des différents membres de la famille quant aux relations au sein de la famille et a indiqué que, par comparaison aux adolescents non-anxieux, les adolescents anxieux étaient plus enclins à éprouver un sentiment d'autonomie individuelle diminué par rapport à leurs parents. Finalement, une troisième étude s'est intéressée à déterminer l'impact d'expériences d'apprentissage moins directes dans l'étiologie de l'anxiété. Les résultats ont indiqué que les mères présentant un trouble panique étaient plus enclines à s'engager dans des comportements qui maintiennent la panique et à impliquer leurs enfants dans ces comportements, que les mères ne présentant pas de trouble panique. En se basant sur des recherches antérieures qui ont établi une relation entre le contrôle parental, la perception de contrôle chez l'enfant et les troubles anxieux, le présent travail non seulement confirme ce lien mais propose également un modèle pour résumer l'état actuel des connaissances concernant les processus familiaux et le développement des troubles anxieux. Deux routes ont été suggérées par lesquelles l'anxiété pourrait être transmise de manière intergénérationnelle. Chacune de ces routes attribue un rôle important à la perception de contrôle chez l'enfant. L'idée est que lorsque les enfants présentent une prédisposition à interpréter le comportement de leurs parents comme hors de leur contrôle, ils seraient plus enclins à développer de l'anxiété. A ce titre, la perception du contrôle représenterait un tampon entre le comportement de contrôle/surprotection des parents et le trouble anxieux chez l'enfant. - The principal objective of the present work was to explore parent-child relationships and family learning processes associated with anxiety disorders. To this purpose, families with and without an anxious family member (mother or child) were compared. In a first study, observation of mother-child interaction, during a standard play situation, revealed that mothers with panic disorder were more likely to display verbal control and criticism, and less likely to display sensitivity toward their children than mothers without panic disorder. A second study examined family members' perceptions of family relationships and indicated that compared to non-anxious adolescents, anxious adolescents were more prone to experience a diminished sense of individual autonomy in relation to their parents. Finally a third study was interested in determining the effect of less direct learning experiences in the aetiology of anxiety. Results indicated that mothers with panic disorder were more likely to engage in panic-maintaining behaviour and to involve their children in this behaviour than mothers without panic disorder. Based on previous research showing a relationship between parental control, children's perception of control, and anxiety disorders, the present work not only further adds evidence to support this link but also proposes a model summarizing the current knowledge concerning family processes and the development of anxiety disorders. Two pathways have been suggested through which anxiety may be intergenerationally transmitted. Both pathways assign an important role to children's perception of control. The idea is that whenever children have a predisposition towards interpreting their parents' behaviour as beyond of their control, they may be more prone to develop anxiety. As such, perceived control may represent a buffer between parental overcontrolling/overprotective behaviours and childhood anxiety disorder.

Relationships between imatinib plasma levels and efficacy

Purpose: While imatinib has revolutionized the treatment of chronic myeloid leukaemia (CML) and gastrointestinal stromal tumors (GIST), its pharmacokinetic-pharmacodynamic relationships have been poorly studied. This study aimed to explore the issue in oncologic patients, and to evaluate the specific influence of the target genotype in a GIST subpopulation. Patients and methods: Data from 59 patients (321 plasma samples) were collected during a previous pharmacokinetic study. Based on a population model purposely developed, individual post-hoc Bayesian estimates of pharmacokinetic parameters were derived, and used to estimate drug exposure (AUC; area under curve). Free fraction parameters were deduced from a model incorporating plasma alpha1-acid glycoprotein levels. Associations between AUC (or clearance) and therapeutic response (coded on a 3-point scale), or tolerability (4-point scale), were explored by ordered logistic regression. Influence of KIT genotype on response was also assessed in GIST patients. Results: Total and free drug exposure correlated with the number of side effects (p < 0.005). A relationship with response was not evident in the whole patient set (with good-responders tending to receive lower doses and bad-responders higher doses). In GIST patients however, higher free drug exposure predicted better responses. A strong association was notably observed in patients harboring an exon 9 mutation or a wild type KIT, known to decrease tumor sensitivity towards imatinib (p < 0.005). Conclusions: Our results are arguments to further evaluate the potential benefit of a therapeutic monitoring program for imatinib. Our data also suggest that stratification by genotype will be important in future trials.

PHYTOCHROME KINASE SUBSTRATE4 modulates phytochrome-mediated control of hypocotyl growth orientation

Gravity and light are major factors shaping plant growth. Light perceived by phytochromes leads to seedling deetiolation, which includes the deviation from vertical hypocotyl growth and promotes hypocotyl phototropism. These light responses enhance survival of young seedlings during their emergence from the soil. The PHYTOCHROME KINASE SUBSTRATE (PKS) family is composed of four members in Arabidopsis (Arabidopsis thaliana): PKS1 to PKS4. Here we show that PKS4 is a negative regulator of both phytochrome A- and B-mediated inhibition of hypocotyl growth and promotion of cotyledon unfolding. Most prominently, pks4 mutants show abnormal phytochrome-modulated hypocotyl growth orientation. In dark-grown seedlings hypocotyls change from the original orientation defined by seed position to the upright orientation defined by gravity and light reduces the magnitude of this shift. In older seedlings with the hypocotyls already oriented by gravity, light promotes the deviation from vertical orientation. Based on the characterization of pks4 mutants we propose that PKS4 inhibits changes in growth orientation under red or far-red light. Our data suggest that in these light conditions PKS4 acts as an inhibitor of asymmetric growth. This hypothesis is supported by the phenotype of PKS4 overexpressers. Together with previous findings, these results indicate that the PKS family plays important functions during light-regulated tropic growth responses

Dimensionality of the Rosenberg self-esteem scale and its relationships with the three- and five-factor personality models

The authors investigated the dimensionality of the French version of the Rosenberg Self-Esteem Scale (RSES; Rosenberg, 1965) using confirmatory factor analysis. We tested models of 1 or 2 factors. Results suggest the RSES is a 1-dimensional scale with 3 highly correlated items. Comparison with the Revised NEO-Personality Inventory (NEO-PI-R; Costa, McCrae, & Rolland, 1998) demonstrated that Neuroticism correlated strongly and Extraversion and Conscientiousness moderately with the RSES. Depression accounted for 47% of the variance of the RSES. Other NEO-PI-R facets were also moderately related with self-esteem.

Authority relationships between obedience and disobedience

Recent episodes of public dissent (such as the demonstrations against G8 policies) raise the issue of the psychological processes triggered in obeying and disobeying the authority. Even if obedience to authority is an important aspect of social life and it plays a key role in maintaining social order, the concept of obedience has been studied in social psychology mainly in terms of its destructive aspects. Besides, most of the studies have overlooked the role of disobedience in the authority relationship. Disobedience may be conceived of as a protest that undermines the legitimacy of the authority or it can represent an instrument for controlling the legitimacy of the authority's demands, becoming a factor protecting against authoritarianism. In this article, a new perspective on the study of the relationship between the individual and the authority is put forward, considering obedience and disobedience as parallel concepts, each having constructive and destructive aspects. 2008 Elsevier Ltd. All rights reserved.

Correlation of tumor-associated antigens MAGE, NY-ESO-1 and P53 expression with clinical and pathological relationships of patients with oral squamous cell carcinoma

Despite advances in the diagnosisand treatment of head and neck cancer,survival rates have not improvedover recent years. New therapeuticstrategies, including immunotherapy,are the subject of extensive research.In several types of tumors, the presenceof tumor infiltrating lymphocytes(TILs), notably CD8+ T cellsand dendritic cells, has been correlatedwith improved prognosis. Moreover,some T cells among TILs havebeen shown to kill tumor cells in vitroupon recognition of tumor-associatedantigens. Tumor associated antigensare expressed in a significant proportionof squamous cell carcinoma ofthe head and neck and apparently mayplay a role in the regulation of cancercell growth notably by inhibition ofp53 protein function in some cancers.The MAGE family CT antigens couldtherefore potentially be used as definedtargets for immunotherapy andtheir study bring new insight in tumorgrowth regulation mechanisms. Between1995 - 2005 54 patients weretreated surgically in our institution forsquamous cell carcinoma of the oralcavity. Patient and clinical data wasobtained from patient files and collectedinto a computerized database.For each patient, paraffin embeddedtumor specimens were retrieved andexpression of MAGE CT antigens,p53, NY-OESO-1 were analyzed byimmunohistochemistry. Results werethen correlated with histopathologicalparameter such as tumor depth,front invasion according to Bryne andboth, local control and disease freesurvival. MAGE-A was expressed in52% of patients. NY-ESO-1 and p53expression was found in 7% and 52%cases respectively. A higher tumordepth was significantly correlatedwith expression of MAGE-Aproteins(p = 0.03). No significant correlationcould be made between the expressionof both p53 andNY-OESO-1 andhistopathological parameters. Expressionof tumor-associated antigendid not seem to impact significantlyon patient prognosis. As does thedemonstration of p53 function inhibitionby CT antigens of MAGE family,our results suggest, that tumor associatedantigens may be implicated in tumorprogression mechanisms. Thishypothesis need further investigationto clarify the relationship betweenhost immune response and local tumorbiology.

Simulation-based systematic review of imatinib population pharmacokinetics and PK-PD relationships in chronic myeloid leukemia (CML) patients

Objectives: Several population pharmacokinetic (PPK) and pharmacokinetic-pharmacodynamic (PK-PD) analyses have been performed with the anticancer drug imatinib. Inspired by the approach of meta-analysis, we aimed to compare and combine results from published studies in a useful way - in particular for improving the clinical interpretation of imatinib concentration measurements in the scope of therapeutic drug monitoring (TDM). Methods: Original PPK analyses and PK-PD studies (PK surrogate: trough concentration Cmin; PD outcomes: optimal early response and specific adverse events) were searched systematically on MEDLINE. From each identified PPK model, a predicted concentration distribution under standard dosage was derived through 1000 simulations (NONMEM), after standardizing model parameters to common covariates. A "reference range" was calculated from pooled simulated concentrations in a semi-quantitative approach (without specific weighting) over the whole dosing interval. Meta-regression summarized relationships between Cmin and optimal/suboptimal early treatment response. Results: 9 PPK models and 6 relevant PK-PD reports in CML patients were identified. Model-based predicted median Cmin ranged from 555 to 1388 ng/ml (grand median: 870 ng/ml and inter-quartile range: 520-1390 ng/ml). The probability to achieve optimal early response was predicted to increase from 60 to 85% from 520 to 1390 ng/ml across PK-PD studies (odds ratio for doubling Cmin: 2.7). Reporting of specific adverse events was too heterogeneous to perform a regression analysis. The general frequency of anemia, rash and fluid retention increased however consistently with Cmin, but less than response probability. Conclusions: Predicted drug exposure may differ substantially between various PPK analyses. In this review, heterogeneity was mainly attributed to 2 "outlying" models. The established reference range seems to cover the range where both good efficacy and acceptable tolerance are expected for most patients. TDM guided dose adjustment appears therefore justified for imatinib in CML patients. Its usefulness remains now to be prospectively validated in a randomized trial.

Reliable acetabular cup orientation with a new gravity-assisted guidance system.

Acetabular cup orientation is a key factor determining hip stability, and standard mechanical guides have shown little help in improving alignment. An in vitro study was carried out to compare the accuracy and precision of a new gravity-assisted guidance system with a standard mechanical guide. Three hundred ten cups were impacted by 5 surgeons, and the final cup orientation was measured. With the new guide, the average error in anteversion was 0.4 degrees , compared with 10.4 degrees with the standard guide and 0.3 degrees and -4.7 degrees , respectively, for abduction angles. The average time required for orienting the cups was similar for both guides. The accuracy and reproducibility obtained with the new guide were better (P < .0001). These good results would require a clinical validation.

Efficacité du counseling d'orientation: impacts de l'alliance de travail et du contexte psychosocial

La problématique centrale de cette thèse de doctorat est l'efficacité de l'accompagnement à l'orientation. Elle renvoie en particulier à la multiplicité des types d'interventions ainsi qu'aux tensions entre les finalités de l'orientation qui rendent improbable une mesure univoque et objective de l'efficacité des pratiques. Le «mythe » de l'efficacité trouve notamment sa source dans le persistent monopole du modèle de l'appariement qui a largement influencé le développement de la discipline. Le manuscrit est basé sur deux études empiriques. Premièrement, « voies professionnelles » est une étude longitudinale visant l'évaluation de l'efficacité d'un service de counseling d'orientation au travers de mesures intraindividuelles. Les résultats immédiats (pre-post) indiquent une forte diminution de l'indécision vocationnelle des consultants ainsi qu'une augmentation de leur bien-être. Les résultats longitudinaux sur un an indiquent une évolution positive des difficultés plus ancrées ainsi qu'un fort taux d'implémentation des projets professionnels. La qualité de l'alliance de travail démontre un impact positif sur l'efficacité de la démarche. Deuxièmement, l'étude « orientation et genre » a permis de mettre en évidence un effet d'interaction entre le sexe et le niveau scolaire d'élèves en fin de scolarité sur leurs profils d'intérêts professionnels. Ce résultat affecte en particulier les jeunes filles dans une filière à exigences élémentaires car ces deux identités psychosociales semblent restreindre doublement les options professionnelles envisageables. Les deux études ont permis de soulever cinq implications centrales : (1) La distinction entre les aspects cognitifs et émotionnels de l'indécision vocationnelle est importante. En particulier, la préparation au choix est un construit qui nécessite clarification ; (2) Les processus de transitions professionnelles ainsi que leur accompagnement doivent être considérés dans leur dimension temporelle ; (3) L'interconnexion des différentes sphères de vie est centrale dans les processus d'orientation et leur accompagnement ; (4) L'efficacité du conseil en orientation est affectée par la qualité des aspects relationnels ; (5) La complexité des pratiques et de leurs finalités confronte l'orientation à son rôle envers des identités psychosociales fragilisées. - The central issue of this doctoral thesis is the effectiveness of career counseling and guidance. In particular, this refers to the many types of career interventions as well as the tensions between their objectives. Those aspects make it unlikely to get an unambiguous and objective measure of the effectiveness of career practices. The "myth of efficiency" is particularly rooted in the persistent monopoly of person-environment fit models, which greatly influenced the development of the discipline. This manuscript is based on two empirical studies. First, "career paths" is a longitudinal study looking at the effectiveness of a career counseling service through intraindividual measures. Pre-post impacts showed a significant decrease in clients' vocational indecision as well as a moderate increase in their well-being. The one year-longitudinal results highlighted significant decreases in more constant decision-making difficulties with a high proportion of clients having implemented their professional projects. The quality of the working alliance had a positive impact on the effectiveness of the intervention. The second study, "vocational development and gender" highlighted an interaction effect between late schoolchildren's gender and school level on their professional interests profile. This result particularly affected girls at a low school level, because these psychosocial identities were a double restraint in restricting career options. The two studies raised five central implications: (1) The distinction between cognitive and emotional aspects of vocational indecision is important. In particular, readiness to make a choice is a construct that requires clarification; (2) career transitions processes as well as supporting these transitions, should be considered in their temporal dimension (3) the interconnection of different spheres of life is central to vocational development and career guidance and counseling; (4) the effectiveness of career counseling is affected by the quality of the relational aspects in the intervention; (5) and the complexity of career interventions and their objectives forces practitioners to consider their role and responsibilities towards clients with marginalized psychosocial identities.

Probability of achieving optimal molecular response to imatinib in chronic myeloid leukemia (CML) patients: Pharmacokinetic/Pharmacodynamic (PK/PD) relationships observed under field-conditions

Objectives: Imatinib has been increasingly proposed for therapeutic drug monitoring (TDM), as trough concentrations (Cmin) correlate with response rates in CML patients. This analysis aimed to evaluate the impact of imatinib exposure on optimal molecular response rates in a large European cohort of patients followed by centralized TDM.¦Methods: Sequential PK/PD analysis was performed in NONMEM 7 on 2230 plasma (PK) samples obtained along with molecular response (PD) data from 1299 CML patients. Model-based individual Bayesian estimates of exposure, parameterized as to initial dose adjusted and log-normalized Cmin (log-Cmin) or clearance (CL), were investigated as potential predictors of optimal molecular response, while accounting for time under treatment (stratified at 3 years), gender, CML phase, age, potentially interacting comedication, and TDM frequency. PK/PD analysis used mixed-effect logistic regression (iterative two-stage method) to account for intra-patient correlation.¦Results: In univariate analyses, CL, log-Cmin, time under treatment, TDM frequency, gender (all p<0.01) and CML phase (p=0.02) were significant predictors of the outcome. In multivariate analyses, all but log-Cmin remained significant (p<0.05). Our model estimates a 54.1% probability of optimal molecular response in a female patient with a median CL of 14.4 L/h, increasing by 4.7% with a 35% decrease in CL (percentile 10 of CL distribution), and decreasing by 6% with a 45% increased CL (percentile 90), respectively. Male patients were less likely than female to be in optimal response (odds ratio: 0.62, p<0.001), with an estimated probability of 42.3%.¦Conclusions: Beyond CML phase and time on treatment, expectedly correlated to the outcome, an effect of initial imatinib exposure on the probability of achieving optimal molecular response was confirmed in field-conditions by this multivariate analysis. Interestingly, male patients had a higher risk of suboptimal response, which might not exclusively derive from their 18.5% higher CL, but also from reported lower adherence to the treatment. A prospective longitudinal study would be desirable to confirm the clinical importance of identified covariates and to exclude biases possibly affecting this observational survey.