Organization and plasticity of auditory spatial representations

Spatial hearing refers to a set of abilities enabling us to determine the location of sound sources, redirect our attention toward relevant acoustic events, and recognize separate sound sources in noisy environments. Determining the location of sound sources plays a key role in the way in which humans perceive and interact with their environment. Deficits in sound localization abilities are observed after lesions to the neural tissues supporting these functions and can result in serious handicaps in everyday life. These deficits can, however, be remediated (at least to a certain degree) by the surprising capacity of reorganization that the human brain possesses following damage and/or learning, namely, the brain plasticity. In this thesis, our aim was to investigate the functional organization of auditory spatial functions and the learning-induced plasticity of these functions. Overall, we describe the results of three studies. The first study entitled "The role of the right parietal cortex in sound localization: A chronometric single pulse transcranial magnetic stimulation study" (At et al., 2011), study A, investigated the role of the right parietal cortex in spatial functions and its chronometry (i.e. the critical time window of its contribution to sound localizations). We concentrated on the behavioral changes produced by the temporarily inactivation of the parietal cortex with transcranial magnetic stimulation (TMS). We found that the integrity of the right parietal cortex is crucial for localizing sounds in the space and determined a critical time window of its involvement, suggesting a right parietal dominance for auditory spatial discrimination in both hemispaces. In "Distributed coding of the auditory space in man: evidence from training-induced plasticity" (At et al., 2013a), study B, we investigated the neurophysiological correlates and changes of the different sub-parties of the right auditory hemispace induced by a multi-day auditory spatial training in healthy subjects with electroencephalography (EEG). We report a distributed coding for sound locations over numerous auditory regions, particular auditory areas code specifically for precise parts of the auditory space, and this specificity for a distinct region is enhanced with training. In the third study "Training-induced changes in auditory spatial mismatch negativity" (At et al., 2013b), study C, we investigated the pre-attentive neurophysiological changes induced with a training over 4 days in healthy subjects with a passive mismatch negativity (MMN) paradigm. We showed that training changed the mechanisms for the relative representation of sound positions and not the specific lateralization themselves and that it changed the coding in right parahippocampal regions. - L'audition spatiale désigne notre capacité à localiser des sources sonores dans l'espace, de diriger notre attention vers les événements acoustiques pertinents et de reconnaître des sources sonores appartenant à des objets distincts dans un environnement bruyant. La localisation des sources sonores joue un rôle important dans la façon dont les humains perçoivent et interagissent avec leur environnement. Des déficits dans la localisation de sons sont souvent observés quand les réseaux neuronaux impliqués dans cette fonction sont endommagés. Ces déficits peuvent handicaper sévèrement les patients dans leur vie de tous les jours. Cependant, ces déficits peuvent (au moins à un certain degré) être réhabilités grâce à la plasticité cérébrale, la capacité du cerveau humain à se réorganiser après des lésions ou un apprentissage. L'objectif de cette thèse était d'étudier l'organisation fonctionnelle de l'audition spatiale et la plasticité induite par l'apprentissage de ces fonctions. Dans la première étude intitulé « The role of the right parietal cortex in sound localization : A chronometric single pulse study » (At et al., 2011), étude A, nous avons examiné le rôle du cortex pariétal droit dans l'audition spatiale et sa chronométrie, c'est-à- dire le moment critique de son intervention dans la localisation de sons. Nous nous sommes concentrés sur les changements comportementaux induits par l'inactivation temporaire du cortex pariétal droit par le biais de la Stimulation Transcrânienne Magnétique (TMS). Nous avons démontré que l'intégrité du cortex pariétal droit est cruciale pour localiser des sons dans l'espace. Nous avons aussi défini le moment critique de l'intervention de cette structure. Dans « Distributed coding of the auditory space : evidence from training-induced plasticity » (At et al., 2013a), étude B, nous avons examiné la plasticité cérébrale induite par un entraînement des capacités de discrimination auditive spatiale de plusieurs jours. Nous avons montré que le codage des positions spatiales est distribué dans de nombreuses régions auditives, que des aires auditives spécifiques codent pour des parties données de l'espace et que cette spécificité pour des régions distinctes est augmentée par l'entraînement. Dans « Training-induced changes in auditory spatial mismatch negativity » (At et al., 2013b), étude C, nous avons examiné les changements neurophysiologiques pré- attentionnels induits par un entraînement de quatre jours. Nous avons montré que l'entraînement modifie la représentation des positions spatiales entraînées et non-entrainées, et que le codage de ces positions est modifié dans des régions parahippocampales.

The knock-out of ARP3a gene affects F-actin cytoskeleton organization altering cellular tip growth, morphology and development in moss Physcomitrella patens.

The seven subunit Arp2/3 complex is a highly conserved nucleation factor of actin microfilaments. We have isolated the genomic sequence encoding a putative Arp3a protein of the moss Physcomitrella patens. The disruption of this ARP3A gene by allele replacement has generated loss-of-function mutants displaying a complex developmental phenotype. The loss-of function of ARP3A gene results in shortened, almost cubic chloronemal cells displaying affected tip growth and lacking differentiation to caulonemal cells. In moss arp3a mutants, buds differentiate directly from chloronemata to form stunted leafy shoots having differentiated leaves similar to wild type. Yet, rhizoids never differentiate from stem epidermal cells. To characterize the F-actin organization in the arp3a-mutated cells, we disrupted ARP3A gene in the previously described HGT1 strain expressing conditionally the GFP-talin marker. In vivo observation of the F-actin cytoskeleton during P. patens development demonstrated that loss-of-function of Arp3a is associated with the disappearance of specific F-actin cortical structures associated with the establishment of localized cellular growth domains. Finally, we show that constitutive expression of the P. patens Arp3a and its Arabidopsis thaliana orthologs efficiently complement the mutated phenotype indicating a high degree of evolutionary conservation of the Arp3 function in land plants.

Stochastic inversion of tracer test and electrical geophysical data to estimate hydraulic conductivities.

Quantifying the spatial configuration of hydraulic conductivity (K) in heterogeneous geological environments is essential for accurate predictions of contaminant transport, but is difficult because of the inherent limitations in resolution and coverage associated with traditional hydrological measurements. To address this issue, we consider crosshole and surface-based electrical resistivity geophysical measurements, collected in time during a saline tracer experiment. We use a Bayesian Markov-chain-Monte-Carlo (McMC) methodology to jointly invert the dynamic resistivity data, together with borehole tracer concentration data, to generate multiple posterior realizations of K that are consistent with all available information. We do this within a coupled inversion framework, whereby the geophysical and hydrological forward models are linked through an uncertain relationship between electrical resistivity and concentration. To minimize computational expense, a facies-based subsurface parameterization is developed. The Bayesian-McMC methodology allows us to explore the potential benefits of including the geophysical data into the inverse problem by examining their effect on our ability to identify fast flowpaths in the subsurface, and their impact on hydrological prediction uncertainty. Using a complex, geostatistically generated, two-dimensional numerical example representative of a fluvial environment, we demonstrate that flow model calibration is improved and prediction error is decreased when the electrical resistivity data are included. The worth of the geophysical data is found to be greatest for long spatial correlation lengths of subsurface heterogeneity with respect to wellbore separation, where flow and transport are largely controlled by highly connected flowpaths.

The branch-site test of positive selection is surprisingly robust but lacks power under synonymous substitution saturation and variation in GC

Positive selection is widely estimated from protein coding sequence alignments by the nonsynonymous-to-synonymous ratio omega. Increasingly elaborate codon models are used in a likelihood framework for this estimation. Although there is widespread concern about the robustness of the estimation of the omega ratio, more efforts are needed to estimate this robustness, especially in the context of complex models. Here, we focused on the branch-site codon model. We investigated its robustness on a large set of simulated data. First, we investigated the impact of sequence divergence. We found evidence of underestimation of the synonymous substitution rate for values as small as 0.5, with a slight increase in false positives for the branch-site test. When dS increases further, underestimation of dS is worse, but false positives decrease. Interestingly, the detection of true positives follows a similar distribution, with a maximum for intermediary values of dS. Thus, high dS is more of a concern for a loss of power (false negatives) than for false positives of the test. Second, we investigated the impact of GC content. We showed that there is no significant difference of false positives between high GC (up to similar to 80%) and low GC (similar to 30%) genes. Moreover, neither shifts of GC content on a specific branch nor major shifts in GC along the gene sequence generate many false positives. Our results confirm that the branch-site is a very conservative test.

Indeterminate test results of T-SPOT.TB performed under routine field conditions

Interferon-gamma release assays for the diagnosis of tuberculosis (TB) can give indeterminate results. The prevalence of indeterminate test results (ITRs) among T-SPOT.TB tests was assessed. A retrospective analysis of samples processed in 2005 was performed. ITRs were assessed by age, sex, immunosuppression, distance to the laboratory and season. A subgroup of tests performed for specific indications (contact tracing, migrants with positive tuberculin skin test, TB suspects and immunosuppression) were analysed separately. Of a total of 1,429 tests, 49 (3.4%) were indeterminate. ITRs were significantly associated with old age (>75 versus 5-75 yrs; odds ratio (OR) 7.97, 95% confidence interval (CI) 3.968-15.438) and the season during which samples were transported (autumn and winter versus spring and summer; OR 3.47, 95% CI 1.753-7.514). The incidence of ITR was 302 (2.0%) among TB contacts, 75 (1.6%) among immigrants, 156 (3.0%) in TB suspects and 32 (3.0%) among immunosuppressed patients. Sex, young age and distance to the laboratory were not associated with the rate of ITR. Of the 13 tests with ITR that were repeated, 10 gave a clear positive or negative result. Indeterminate test results with T-SPOT.TB under routine conditions were infrequent and more common in individuals aged >75 yrs than in children and younger adults. The incidence of indeterminate test results was low and similar among healthy tuberculosis contacts, immigrants with a positive tuberculin skin test, tuberculosis suspects and the immunosuppressed. The conditions of transportation may influence the incidence of indeterminate test results.

Measurement of the whole body clearance of infused glycerol as a test of liver function after major hepatectomy.

Major liver resection can be used in the treatment of liver cancer. The functional capacity of liver parenchyma needs to be evaluated preoperatively because it conditions the outcome. We assessed whether the whole body clearance of glycerol, a substrate essentially metabolized in liver cells, may be suitable as a simple test of liver function. Seven patients after major hepatectomy, six patients after colectomy and 12 healthy subjects were studied. Patients were investigated on the first day after surgery. All participants were studied during a 150-min basal period followed by a 120-min infusion of 16 mumol kg-1 min-1 13C-labelled glycerol. Whole body glycerol clearance was calculated from the change in plasma glycerol concentration. Whole body glucose production was measured with 6,6 2H2 glucose infused as a tracer in the basal state and during glycerol infusion. In addition, 13C glucose synthesis was monitored to quantitate gluconeogenesis from glycerol. Patients after liver resection had higher plasma glycerol concentrations and lower whole body glycerol clearance than healthy subjects and patients after colectomy. They also had higher plasma glucagon concentrations. Their fasting glucose production was mildly elevated in the fasting state and did not change after glycerol infusion, indicating a normal hepatic autoregulation of glucose production. These results indicate that whole body glycerol clearance can be simply determined from plasma glycerol concentrations during exogenous glycerol infusion. It is significantly reduced in patients after major hepatectomy, suggesting that it constitutes a sensitive test of hepatic function. Its use as a preoperative testing procedure remains to be evaluated.

Latent tuberculosis: which test in which situation?

Detection of latent tuberculosis infection (LTBI) is a cost-effective procedure in patients at high risk of developing tuberculosis later and who could benefit from preventive treatment. The commonest situation where screening is indicated is the search for infected contacts of an index case with pulmonary tuberculosis. As a screening procedure the current tendency is to replace the time-honoured tuberculin skin test by one of the new blood tests measuring the release of interferon gamma by sensitised T lymphocytes after stimulation by specific peptides from M. tuberculosis. The main advantage of the new tests is the absence of interference with BCG and non-tuberculous mycobacteria, which confers high specificity on the test. This allows a more selective choice of persons for whom preventive treatment is indicated. Some controversial issues remain, such as sensitivity in children and immunocompromised subjects, the predictive value of the blood test and interpretation of possible changes in test results over time. The technical aspects required for performance of the tests must be considered.

Métropolisation, morphologie urbaine et développement durable : transformations urbaines et régulation de l'étalement : le cas de l'agglomération lausannoise

Résumé Métropolisation, morphologie urbaine et développement durable. Transformations urbaines et régulation de l'étalement : le cas de l'agglomération lausannoise. Cette thèse s'inscrit clans la perspective d'une analyse stratégique visant à un définir et à expliciter les liens entre connaissance, expertise et décision politique. L'hypothèse fondamentale qui oriente l'ensemble de ce travail est la suivante : le régime d'urbanisation qui s'est imposé au cours des trente dernières années correspond à une transformation du principe morphogénétique de développement spatial des agglomérations qui tend à alourdir leurs bilans écologiques et à péjorer la qualité du cadre de vie des citadins. Ces enjeux environnementaux liés aux changements urbains et singulièrement ceux de la forme urbaine constituent un thème de plus en plus important dans la recherche de solutions d'aménagement urbain dans une perspective de développement durable. Dans ce contexte, l'aménagement urbain devient un mode d'action et une composante de tout premier ordre des politiques publiques visant un développement durable à l'échelle locale et globale. Ces modalités de développement spatial des agglomérations émergent indiscutablement au coeur de la problématique environnementale. Or si le concept de développement durable nous livre une nouvelle de de lecture des territoires et de ses transformations, en prônant le modèle de la ville compacte et son corollaire la densification, la traduction à donner à ce principe stratégique reste controversée, notamment sous l'angle de l'aménagement du territoire et des stratégies de développement urbain permettant une mise en oeuvre adéquate des solutions proposées. Nous avons ainsi tenté dans ce travail de répondre à un certain nombre de questions : quelle validité accorder au modèle de la ville compacte ? La densification est-elle une réponse adéquate ? Si oui, sous quelles modalités ? Quelles sont, en termes de stratégies d'aménagement, les alternatives durables au modèle de la ville étalée ? Faut-il vraiment densifier ou simplement maîtriser la dispersion ? Notre objectif principal étant in fine de déterminer les orientations et contenus urbanistiques de politiques publiques visant à réguler l'étalement urbain, de valider la faisabilité de ces principes et à définir les conditions de leur mise en place dans le cas d'une agglomération. Pour cela, et après avoir choisi l'agglomération lausannoise comme terrain d'expérimentation, trois approches complémentaires se sont révélées indispensables dans ce travail 1. une approche théorique visant à définir un cadre conceptuel interdisciplinaire d'analyse du phénomène urbain dans ses rapports à la problématique du développement durable liant régime d'urbanisation - forme urbaine - développement durable ; 2. une approche méthodologique proposant des outils d'analyse simples et efficaces de description des nouvelles morphologies urbaines pour une meilleure gestion de l'environnement urbain et de la pratique de l'aménagement urbain ; 3. une approche pragmatique visant à approfondir la réflexion sur la ville étalée en passant d'une approche descriptive des conséquences du nouveau régime d'urbanisation à une approche opérationnelle, visant à identifier les lignes d'actions possibles dans une perspective de développement durable. Cette démarche d'analyse nous a conduits à trois résultats majeurs, nous permettant de définir une stratégie de lutte contre l'étalement. Premièrement, si la densification est acceptée comme un objectif stratégique de l'aménagement urbain, le modèle de la ville dense ne peut être appliqué saris la prise en considération d'autres objectifs d'aménagement. Il ne suffit pas de densifier pour réduire l'empreinte écologique de la ville et améliorer la qualité de vie des citadins. La recherche d'une forme urbaine plus durable est tributaire d'une multiplicité de facteurs et d'effets de synergie et la maîtrise des effets négatifs de l'étalement urbain passe par la mise en oeuvre de politiques urbaines intégrées et concertées, comme par exemple prôner la densification qualifiée comme résultante d'un processus finalisé, intégrer et valoriser les transports collectifs et encore plus la métrique pédestre avec l'aménagement urbain, intégrer systématiquement la diversité à travers les dimensions physique et sociale du territoire. Deuxièmement, l'avenir de ces territoires étalés n'est pas figé. Notre enquête de terrain a montré une évolution des modes d'habitat liée aux modes de vie, à l'organisation du travail, à la mobilité, qui font que l'on peut penser à un retour d'une partie de la population dans les villes centres (fin de la toute puissance du modèle de la maison individuelle). Ainsi, le diagnostic et la recherche de solutions d'aménagement efficaces et viables ne peuvent être dissociés des demandes des habitants et des comportements des acteurs de la production du cadre bâti. Dans cette perspective, tout programme d'urbanisme doit nécessairement s'appuyer sur la connaissance des aspirations de la population. Troisièmement, la réussite de la mise en oeuvre d'une politique globale de maîtrise des effets négatifs de l'étalement urbain est fortement conditionnée par l'adaptation de l'offre immobilière à la demande de nouveaux modèles d'habitat répondant à la fois à la nécessité d'une maîtrise des coûts de l'urbanisation (économiques, sociaux, environnementaux), ainsi qu'aux aspirations émergentes des ménages. Ces résultats nous ont permis de définir les orientations d'une stratégie de lutte contre l'étalement, dont nous avons testé la faisabilité ainsi que les conditions de mise en oeuvre sur le territoire de l'agglomération lausannoise. Abstract This dissertation participates in the perspective of a strategic analysis aiming at specifying the links between knowledge, expertise and political decision, The fundamental hypothesis directing this study assumes that the urban dynamics that has characterized the past thirty years signifies a trans-formation of the morphogenetic principle of agglomerations' spatial development that results in a worsening of their ecological balance and of city dwellers' quality of life. The environmental implications linked to urban changes and particularly to changes in urban form constitute an ever greater share of research into sustainable urban planning solutions. In this context, urban planning becomes a mode of action and an essential component of public policies aiming at local and global sustainable development. These patterns of spatial development indisputably emerge at the heart of environmental issues. If the concept of sustainable development provides us with new understanding into territories and their transformations, by arguing in favor of densification, its concretization remains at issue, especially in terms of urban planning and of urban development strategies allowing the appropriate implementations of the solutions offered. Thus, this study tries to answer a certain number of questions: what validity should be granted to the model of the dense city? Is densification an adequate answer? If so, under what terms? What are the sustainable alternatives to urban sprawl in terms of planning strategies? Should densification really be pursued or should we simply try to master urban sprawl? Our main objective being in fine to determine the directions and urban con-tents of public policies aiming at regulating urban sprawl, to validate the feasibility of these principles and to define the conditions of their implementation in the case of one agglomeration. Once the Lausanne agglomeration had been chosen as experimentation field, three complementary approaches proved to be essential to this study: 1. a theoretical approach aiming at definying an interdisciplinary conceptual framework of the ur-ban phenomenon in its relation to sustainable development linking urban dynamics - urban form - sustainable development ; 2. a methodological approach proposing simple and effective tools for analyzing and describing new urban morphologies for a better management of the urban environment and of urban planning practices 3. a pragmatic approach aiming at deepening reflection on urban sprawl by switching from a descriptive approach of the consequences of the new urban dynamics to an operational approach, aiming at identifying possible avenues of action respecting the principles of sustainable development. This analysis approach provided us with three major results, allowing us to define a strategy to cur-tail urban sprawl. First, if densification is accepted as a strategic objective of urban planning, the model of the dense city can not be applied without taking into consideration other urban planning objectives. Densification does not suffice to reduce the ecological impact of the city and improve the quality of life of its dwellers. The search for a more sustainable urban form depends on a multitude of factors and effects of synergy. Reducing the negative effects of urban sprawl requires the implementation of integrated and concerted urban policies, like for example encouraging densification qualified as resulting from a finalized process, integrating and developing collective forms of transportation and even more so the pedestrian metric with urban planning, integrating diversity on a systematic basis through the physical and social dimensions of the territory. Second, the future of such sprawling territories is not fixed. Our research on the ground revea-led an evolution in the modes of habitat related to ways of life, work organization and mobility that suggest the possibility of the return of a part of the population to the center of cities (end of the rule of the model of the individual home). Thus, the diagnosis and the search for effective and sustainable solutions can not be conceived of independently of the needs of the inhabitants and of the behavior of the actors behind the production of the built territory. In this perspective, any urban program must necessarily be based upon the knowledge of the population's wishes. Third, the successful implementation of a global policy of control of urban sprawl's negative effects is highly influenced by the adaptation of property offer to the demand of new habitat models satisfying both the necessity of urbanization cost controls (economical, social, environ-mental) and people's emerging aspirations. These results allowed us to define a strategy to cur-tail urban sprawl. Its feasibility and conditions of implementation were tested on the territory of the Lausanne agglomeration.

Tuberculosis screening in patients with psoriasis before antitumour necrosis factor therapy: comparison of an interferon-gamma release assay vs. tuberculin skin test.

BACKGROUND: Antitumour necrosis factor (anti-TNF) treatments may reactivate latent tuberculosis infection (LTBI). For detecting LTBI, the tuberculin skin test (TST) has low sensitivity and specificity. Interferon-gamma release assays (IGRA) have been shown to be more sensitive and specific than TST. OBJECTIVE: To compare the TST and the T-SPOT.TB IGRA for identifying LTBI in patients with psoriasis before anti-TNF treatment. METHODS: A retrospective study was carried out over a 4-year period on patients with psoriasis requiring anti-TNF treatment. All were subjected to the TST, T-SPOT.TB and chest X-ray. Risk factors for LTBI and history of bacillus Calmette-Guérin (BCG) vaccination were recorded. The association of T-SPOT.TB and TST results with risk factors for LTBI was tested through univariate logistic regression models. Agreement between tests was quantified using kappa statistics. Treatment for LTBI was started 1 month before anti-TNF therapy when indicated. RESULTS: Fifty patients were included; 90% had prior BCG vaccination. A positive T-SPOT.TB was strongly associated with a presumptive diagnosis of LTBI (odds ratio 7.43; 95% confidence interval 1.38-39.9), which was not the case for the TST. Agreement between the T-SPOT.TB and TST was poor, kappa = 0.33 (SD 0.13). LTBI was detected and treated in 20% of the patients. In 20% of the cases, LTBI was not retained in spite of a positive TST but a negative T-SPOT.TB. All patients received an anti-TNF agent for a median of 56 weeks (range 20-188); among patients with a positive TST/negative T-SPOT.TB, no tuberculosis was detected with a median follow-up of 64 weeks (44-188). One case of disseminated tuberculosis occurred after 28 weeks of adalimumab treatment in a patient with LTBI in spite of treatment with rifampicin. CONCLUSION: This study is the first to underline the frequency of LTBI in patients with psoriasis (20%), and to support the use of IGRA instead of the TST for its detection. Nevertheless, there is still a risk of tuberculosis under anti-TNF therapy, even if LTBI is correctly diagnosed and treated.

Etalonnage de trois épreuves de recognition continue : Effets de l'âge, du sexe et du niveau socio-professionnel sur les mesures de discrimination et de biais de réponse. [Standardization of three continuous recognition test forms - Effects of age, sex and socio-economic level on measurements of discrimination and response bias.]

Nous présontons l'étalonnage d'un test mnésique de recognition dans un échantillon de 180 adultes francophones de la Suisse Romande. Le test comprend trois formes utilisant un matériel verbal (mots) ou non verbal (visages ou paysages). Une attention particulière est accordée à l'âge dans la présentation des résultats. Celui-ci affecte plus précocement et plus intensément la performance aux formes non verbales qu'à la forme verbale du test. Il induit également une importante augmentation du nombre de fausses reconnaissances pour les formes non verbales.

Comparison of the organization and fine structure of a chicken and a Xenopus laevis vitellogenin gene.

The structural organization and the coding nucleotide sequence of the Xenopus laevis A2 and the chicken major vitellogenin genes have been compared. Both genes show the same exon-intron organization. However, the degree of homology between the nucleotide and derived amino acid sequences varies extensively along the genes. Several of the 35 exons are quite similar, and a unique cysteine motif in the lipovitellin II domain is conserved between the two genes. In contrast, one internal region is quite divergent. Part of this region encodes phosvitin, which appears to have evolved rapidly by both point mutations and duplications of serines or short other amino acid stretches. On the basis of these observations, we discuss the possible mechanism of evolution of phosvitin in vertebrates.

The Alcohol Use Disorders Identification Test (AUDIT) as a screening tool for excessive drinking in primary care: reliability and validity of a French version.

BACKGROUND: Excessive drinking is a major problem in Western countries. AUDIT (Alcohol Use Disorders Identification Test) is a 10-item questionnaire developed as a transcultural screening tool to detect excessive alcohol consumption and dependence in primary health care settings. OBJECTIVES: The aim of the study is to validate a French version of the Alcohol Use Disorders Identification Test (AUDIT). METHODS: We conducted a validation cross-sectional study in three French-speaking areas (Paris, Geneva and Lausanne). We examined psychometric properties of AUDIT as its internal consistency, and its capacity to correctly diagnose alcohol abuse or dependence as defined by DSM-IV and to detect hazardous drinking (defined as alcohol intake >30 g pure ethanol per day for men and >20 g of pure ethanol per day for women). We calculated sensitivity, specificity, positive and negative predictive values and Receiver Operator Characteristic curves. Finally, we compared the ability of AUDIT to accurately detect "alcohol abuse/dependence" with that of CAGE and MAST. RESULTS: 1207 patients presenting to outpatient clinics (Switzerland, n = 580) or general practitioners' (France, n = 627) successively completed CAGE, MAST and AUDIT self-administered questionnaires, and were independently interviewed by a trained addiction specialist. AUDIT showed a good capacity to discriminate dependent patients (with AUDIT > or =13 for males, sensitivity 70.1%, specificity 95.2%, PPV 85.7%, NPV 94.7% and for females sensitivity 94.7%, specificity 98.2%, PPV 100%, NPV 99.8%); and hazardous drinkers (with AUDIT > or =7, for males sensitivity 83.5%, specificity 79.9%, PPV 55.0%, NPV 82.7% and with AUDIT > or =6 for females, sensitivity 81.2%, specificity 93.7%, PPV 64.0%, NPV 72.0%). AUDIT gives better results than MAST and CAGE for detecting "Alcohol abuse/dependence" as showed on the comparative ROC curves. CONCLUSIONS: The AUDIT questionnaire remains a good screening instrument for French-speaking primary care.