Ascertaining late-life depressive symptoms in Europe: an evaluation of the survey version of the EURO-D scale in 10 nations. The SHARE project.

The reported prevalence of late-life depressive symptoms varies widely between studies, a finding that might be attributed to cultural as well as methodological factors. The EURO-D scale was developed to allow valid comparison of prevalence and risk associations between European countries. This study used Confirmatory Factor Analysis (CFA) and Rasch models to assess whether the goal of measurement invariance had been achieved; using EURO-D scale data collected in 10 European countries as part of the Survey of Health, Ageing and Retirement in Europe (SHARE) (n = 22,777). The results suggested a two-factor solution (Affective Suffering and Motivation) after Principal Component Analysis (PCA) in 9 of the 10 countries. With CFA, in all countries, the two-factor solution had better overall goodness-of-fit than the one-factor solution. However, only the Affective Suffering subscale was equivalent across countries, while the Motivation subscale was not. The Rasch model indicated that the EURO-D was a hierarchical scale. While the calibration pattern was similar across countries, between countries agreement in item calibrations was stronger for the items loading on the affective suffering than the motivation factor. In conclusion, there is evidence to support the EURO-D as either a uni-dimensional or bi-dimensional scale measure of depressive symptoms in late-life across European countries. The Affective Suffering sub-component had more robust cross-cultural validity than the Motivation sub-component.

Mothers' and Fathers' Early Relationship With Their Infant: Similar Yet Temporally Discordant Themes [La relation initiale des parents avec leur nourrisson: Thèmes similaires quoique temporellement discordants]

Objective: To examine first-time mothers' and fathers' themes in their relationship with their infant, how these themes change during the first four months postpartum, and similarities and differences in mothers' and fathers' themes. Participants: Eighteen first-time mother-father couples were separately interviewed at one; six and 16 weeks postpartum. Data Analysis: Audio-taped, transcribed interviews were analysed using a Grounded Theory approach. Results: Our findings reveal a common set of themes for mothers and fathers in relation to the infant : 1: Discovery, 2: Physical Proximity, 3: Emotional Closeness, 4: Initiation of Complementary Interactions and 5: Commitment to Love and Care. However, there was a striking lack of concordance between mothers and fathers for these themes at each point in time. Conclusions: Mothers' and fathers' experience of the early relationship with their infant is unique. Focussing on maternal as well as paternal ways of experiencing the early relationship with their infant sets the way to understanding early developing relationships in the family context.

Placebo effect characteristics observed in a single, international, longitudinal study in Huntington's disease.

BACKGROUND: Classically, clinical trials are based on the placebo-control design. Our aim was to analyze the placebo effect in Huntington's disease. METHODS: Placebo data were obtained from an international, longitudinal, placebo-controlled trial for Huntington's disease (European Huntington's Disease Initiative Study Group). One-hundred and eighty patients were evaluated using the Unified Huntington Disease Rating Scale over 36 months. A placebo effect was defined as an improvement of at least 50% over baseline scores in the Unified Huntington Disease Rating Scale, and clinically relevant when at least 10% of the population met it. RESULTS: Only behavior showed a significant placebo effect, and the proportion of the patients with placebo effect ranged from 16% (first visit) to 41% (last visit). Nondepressed patients with better functional status were most likely to be placebo-responders over time. CONCLUSIONS: In Huntington's disease, behavior seems to be more vulnerable to placebo than overall motor function, cognition, and function

Orthogonal higher order structure and confirmatory factor analysis of the French Wechsler Adult Intelligence Scale (WAIS-III).

According to the most widely accepted Cattell-Horn-Carroll (CHC) model of intelligence measurement, each subtest score of the Wechsler Intelligence Scale for Adults (3rd ed.; WAIS-III) should reflect both 1st- and 2nd-order factors (i.e., 4 or 5 broad abilities and 1 general factor). To disentangle the contribution of each factor, we applied a Schmid-Leiman orthogonalization transformation (SLT) to the standardization data published in the French technical manual for the WAIS-III. Results showed that the general factor accounted for 63% of the common variance and that the specific contributions of the 1st-order factors were weak (4.7%-15.9%). We also addressed this issue by using confirmatory factor analysis. Results indicated that the bifactor model (with 1st-order group and general factors) better fit the data than did the traditional higher order structure. Models based on the CHC framework were also tested. Results indicated that a higher order CHC model showed a better fit than did the classical 4-factor model; however, the WAIS bifactor structure was the most adequate. We recommend that users do not discount the Full Scale IQ when interpreting the index scores of the WAIS-III because the general factor accounts for the bulk of the common variance in the French WAIS-III. The 4 index scores cannot be considered to reflect only broad ability because they include a strong contribution of the general factor.

Assessing depression outcome in patients with moderate dementia: sensitivity of the HoNOS65+ scale.

To date, there is no widely accepted clinical scale to monitor the evolution of depressive symptoms in demented patients. We assessed the sensitivity to treatment of a validated French version of the Health of the Nation Outcome Scale (HoNOS) 65+ compared to five routinely used scales. Thirty elderly inpatients with ICD-10 diagnosis of dementia and depression were evaluated at admission and discharge using paired t-test. Using the Brief Psychiatric Rating Scale (BPRS) "depressive mood" item as gold standard, a receiver operating characteristic curve (ROC) analysis assessed the validity of HoNOS65+F "depressive symptoms" item score changes. Unlike Geriatric Depression Scale, Mini Mental State Examination and Activities of Daily Living scores, BPRS scores decreased and Global Assessment Functioning Scale score increased significantly from admission to discharge. Amongst HoNOS65+F items, "behavioural disturbance", "depressive symptoms", "activities of daily life" and "drug management" items showed highly significant changes between the first and last day of hospitalization. The ROC analysis revealed that changes in the HoNOS65+F "depressive symptoms" item correctly classified 93% of the cases with good sensitivity (0.95) and specificity (0.88) values. These data suggest that the HoNOS65+F "depressive symptoms" item may provide a valid assessment of the evolution of depressive symptoms in demented patients.

Knowledge of Glasgow coma scale by air-rescue physicians

Rapport de synthèse Introduction : Le Glasgow coma score (GCS) est un outil reconnu permettant l'évaluation des patients après avoir subi un traumatisme crânien. Il est réputé pour sa simplicité et sa reproductibilité permettant ainsi aux soignants une évaluation appropriée et continue du status neurologique des patients. Le GCS est composé de trois catégories évaluant la réponse oculaire, verbale et motrice. En Suisse, les soins préhospitaliers aux patients victimes d'un trauma crânien sévère sont effectués par des médecins, essdntiellement à bord des hélicoptères médicalisés. Avant une anesthésie générale nécessaire à ces patients, une évaluation du GCS est essentielle indiquant au personnel hospitalier la gravité des lésions cérébrales. Afin d'évaluer la connaissance du GCS par les médecins à bord des hélicoptères médicalisés en Suisse, nous avons élaboré un questionnaire, contenant dans une première partie des questions sur les connaissances générales du GCS suivi d'un cas clinique. Objectif : Evaluation des connaissances pratiques et théoriques du GCS par les médecins travaillant à bord des hélicoptères médicalisés en Suisse. Méthode : Etude observationnelle prospective et anonymisée à l'aide d'un questionnaire. Evaluation des connaissances générales du GCS et de son utilisation clinique lors de la présentation d'un cas. Résultats : 16 des 18 bases d'hélicoptères médicalisés suisses ont participé à notre étude. 130 questionnaires ont été envoyés et le taux de réponse a été de 79.2%. Les connaissances théoriques du GCS étaient comparables pour tous les médecins indépendamment de leur niveau de formation. Des erreurs dans l'appréciation du cas clinique étaient présentes chez 36.9% des participants. 27.2% ont commis des erreurs dans le score moteur et 18.5% dans le score verbal. Les erreurs ont été répertoriées le plus fréquemment chez les médecins assistants (47.5%, p=0.09), suivi par les chefs de clinique (31.6%, p=0.67) et les médecins installés en cabinet (18.4%, p=1.00). Les médecins cadres ont fait significativement moins d'erreurs que les autres participants (0%, p<0.05). Aucune différence significative n'à été observée entre les différentes spécialités (anesthésie, médecine interne, médecine général et «autres »). Conclusion Même si les connaissances théoriques du GCS sont adéquates parmi les médecins travaillant à bord des hélicoptères médicalisés, des erreurs dans son application clinique sont présentes dans plus d'un tiers des cas. Les médecins avec le moins d'expériences professionnelle font le plus d'erreurs. Au vu de l'importance de l'évaluation correcte du score de Glasgow initial, une amélioration des connaissances est indispensable.

Penetrance of marked cognitive impairment in older male carriers of the FMR1 gene premutation.

BACKGROUND: Male carriers of the FMR1 premutation are at risk of developing the fragile X-associated tremor/ataxia syndrome (FXTAS), a newly recognised and largely under-diagnosed late onset neurodegenerative disorder. Patients affected with FXTAS primarily present with cerebellar ataxia and intention tremor. Cognitive decline has also been associated with the premutation, but the lack of data on its penetrance is a growing concern for clinicians who provide genetic counselling. METHODS: The Mattis Dementia Rating Scale (MDRS) was administered in a double blind fashion to 74 men aged 50 years or more recruited from fragile X families (35 premutation carriers and 39 intrafamilial controls) regardless of their clinical manifestation. Based on previous publications, marked cognitive impairment was defined by a score <or=123 on the MDRS. RESULTS: Both logistic and survival models confirmed that in addition to age and education level, premutation size plays a significant (p<0.01 and p<0.03 for logistic and survival model, respectively) role in cognitive impairment. The estimated penetrance of marked cognitive impairment in our sample (adjusted for the mean age 63.4 years and mean education level 9.7 years) for midsize/large (70-200 CGG) and small (55-69 CGG) premutation alleles was 33.3% (relative risk (RR) 6.5; p = 0.01) and 5.9% (RR 1.15; p = 0.9) respectively. Penetrance in the control group was 5.1%. CONCLUSIONS: Male carriers of midsize to large premutation alleles had a sixfold increased risk of developing cognitive decline and the risk increases with allele size. In addition, it was observed that cognitive impairment may precede motor symptoms. These data provide guidance for genetic counselling although larger samples are required to refine these estimates.

A modular approach for integrative analysis of large-scale gene-expression and drug-response data

High-throughput technologies are now used to generate more than one type of data from the same biological samples. To properly integrate such data, we propose using co-modules, which describe coherent patterns across paired data sets, and conceive several modular methods for their identification. We first test these methods using in silico data, demonstrating that the integrative scheme of our Ping-Pong Algorithm uncovers drug-gene associations more accurately when considering noisy or complex data. Second, we provide an extensive comparative study using the gene-expression and drug-response data from the NCI-60 cell lines. Using information from the DrugBank and the Connectivity Map databases we show that the Ping-Pong Algorithm predicts drug-gene associations significantly better than other methods. Co-modules provide insights into possible mechanisms of action for a wide range of drugs and suggest new targets for therapy

État de stress post-traumatique chez les mères et chez les pères d'enfants prématurés: similitudes et différences = Prematurity and parental post-traumatic stress disorder: similarities and differences

Objectifs Évaluer et comparer la présence de symptômes de stress post-traumatique, en fonction de la gravité de la prématurité, chez les mères et chez les pères de bébés nés prématurément. Méthode En fonction du score de risque périnatal (PERI) du bébé, les parents des prématurés (âge gestationnel moins de 34 semaines) ont été divisés en deux groupes : les parents de prématurés à faible risque (n = 16) et à haut risque (n = 26). Les symptômes d'intrusion et d'évitement, de l'état de stress post-traumatique, ont été évalués chez les parents à l'aide d'un questionnaire, l'Impact of Event Scale (IES). Leurs réponses ont été comparées à un groupe témoin de parents de nouveau-nés à terme (n = 24). Les différences entre les réponses des mères et des pères, ont été analysées. Résultats Les parents de bébés prématurés sont plus à risque que les parents de nouveau-nés à terme de présenter des symptômes de stress post-traumatique. Les mères en lien avec le fait même de la prématurité du bébé, les pères en lien avec la gravité de la prématurité. Les mères et les pères des prématurés des deux groupes (prématurés à faible risque, prématurés à haut risque) décrivent des symptômes d'intrusion, alors que les symptômes d'évitement sont décrits par toutes les mères, mais seulement par les pères de prématurés à haut risque périnatal. Conclusion La naissance prématurée est susceptible d'entraîner l'apparition de symptômes de stress post-traumatique chez les parents. Les mères et les pères réagissent différemment. Objectives Evaluation of the symptoms of parental post-traumatic stress disorder (PTSD), according to the severity of the prematurity, in mothers and fathers of premature babies. Materials and methods According to the Perinatal Risk Inventory (PERI), the parents of premature infants (gestational age less than 34 weeks) were divided into two groups, parents of a low-risk premature infants (n = 16) and of high-risk premature infants (n = 26). The symptoms of intrusion and avoidance, as a part of the post-traumatic stress disorder, were evaluated by an autoadministrated questionnaire, the Impact of Event Scale (IES). Their responses were compared with a control group of parents of full-term infants (n = 24). The differences in the answers of mothers and fathers were analysed. Results The occurrence of symptoms of post-traumatic stress disorder is increased in parents of preterm infants compared with the control group. Whereas mothers of premature infants are at risk of presenting symptoms of PTSD, linked to the prematurity, with fathers the infant perinatal risk factors play a greater role. The symptoms of intrusion are present in mothers and fathers of preterm infants of both groups. Mothers of both groups present avoidance symptoms, although only fathers of high-risk preterm infants present them. Conclusions Premature birth has an impact on both parents in terms of post-traumatic stress reactions. However, mothers and fathers react in different ways according to the severity of the prematurity.

Maintien des capacités des myopathes ou l'art de prescrire l'exercice physique [How to maintain the motor capacities in neuromuscular disorders or the art to prescribe physical exercises].

Optimum management of non-acquired neuromuscular disorders requires a multidisciplinary approach in order to prevent secondary complications related to the progression of the disease and to maintain the patient's independency in daily activities. For treatments, the physiotherapists and occupational therapists must have precise and measurable goals to quantify muscle strength and functions in conjunction with a specialist in neurorehabilitation. Examples of simple motor scores or scales are given in order to transmit precise information to the GP and the multidisciplinary team, and type of orthosis and physiotherapy programmes are given as pieces of advice to assume the follow-up of patients.

Quantitative integration of geophysical and hydraulic data : from the local towards the regional scale range

Des progrès significatifs ont été réalisés dans le domaine de l'intégration quantitative des données géophysique et hydrologique l'échelle locale. Cependant, l'extension à de plus grandes échelles des approches correspondantes constitue encore un défi majeur. Il est néanmoins extrêmement important de relever ce défi pour développer des modèles fiables de flux des eaux souterraines et de transport de contaminant. Pour résoudre ce problème, j'ai développé une technique d'intégration des données hydrogéophysiques basée sur une procédure bayésienne de simulation séquentielle en deux étapes. Cette procédure vise des problèmes à plus grande échelle. L'objectif est de simuler la distribution d'un paramètre hydraulique cible à partir, d'une part, de mesures d'un paramètre géophysique pertinent qui couvrent l'espace de manière exhaustive, mais avec une faible résolution (spatiale) et, d'autre part, de mesures locales de très haute résolution des mêmes paramètres géophysique et hydraulique. Pour cela, mon algorithme lie dans un premier temps les données géophysiques de faible et de haute résolution à travers une procédure de réduction déchelle. Les données géophysiques régionales réduites sont ensuite reliées au champ du paramètre hydraulique à haute résolution. J'illustre d'abord l'application de cette nouvelle approche dintégration des données à une base de données synthétiques réaliste. Celle-ci est constituée de mesures de conductivité hydraulique et électrique de haute résolution réalisées dans les mêmes forages ainsi que destimations des conductivités électriques obtenues à partir de mesures de tomographic de résistivité électrique (ERT) sur l'ensemble de l'espace. Ces dernières mesures ont une faible résolution spatiale. La viabilité globale de cette méthode est testée en effectuant les simulations de flux et de transport au travers du modèle original du champ de conductivité hydraulique ainsi que du modèle simulé. Les simulations sont alors comparées. Les résultats obtenus indiquent que la procédure dintégration des données proposée permet d'obtenir des estimations de la conductivité en adéquation avec la structure à grande échelle ainsi que des predictions fiables des caractéristiques de transports sur des distances de moyenne à grande échelle. Les résultats correspondant au scénario de terrain indiquent que l'approche d'intégration des données nouvellement mise au point est capable d'appréhender correctement les hétérogénéitées à petite échelle aussi bien que les tendances à gande échelle du champ hydraulique prévalent. Les résultats montrent également une flexibilté remarquable et une robustesse de cette nouvelle approche dintégration des données. De ce fait, elle est susceptible d'être appliquée à un large éventail de données géophysiques et hydrologiques, à toutes les gammes déchelles. Dans la deuxième partie de ma thèse, j'évalue en détail la viabilité du réechantillonnage geostatique séquentiel comme mécanisme de proposition pour les méthodes Markov Chain Monte Carlo (MCMC) appliquées à des probmes inverses géophysiques et hydrologiques de grande dimension . L'objectif est de permettre une quantification plus précise et plus réaliste des incertitudes associées aux modèles obtenus. En considérant une série dexemples de tomographic radar puits à puits, j'étudie deux classes de stratégies de rééchantillonnage spatial en considérant leur habilité à générer efficacement et précisément des réalisations de la distribution postérieure bayésienne. Les résultats obtenus montrent que, malgré sa popularité, le réechantillonnage séquentiel est plutôt inefficace à générer des échantillons postérieurs indépendants pour des études de cas synthétiques réalistes, notamment pour le cas assez communs et importants où il existe de fortes corrélations spatiales entre le modèle et les paramètres. Pour résoudre ce problème, j'ai développé un nouvelle approche de perturbation basée sur une déformation progressive. Cette approche est flexible en ce qui concerne le nombre de paramètres du modèle et lintensité de la perturbation. Par rapport au rééchantillonage séquentiel, cette nouvelle approche s'avère être très efficace pour diminuer le nombre requis d'itérations pour générer des échantillons indépendants à partir de la distribution postérieure bayésienne. - Significant progress has been made with regard to the quantitative integration of geophysical and hydrological data at the local scale. However, extending corresponding approaches beyond the local scale still represents a major challenge, yet is critically important for the development of reliable groundwater flow and contaminant transport models. To address this issue, I have developed a hydrogeophysical data integration technique based on a two-step Bayesian sequential simulation procedure that is specifically targeted towards larger-scale problems. The objective is to simulate the distribution of a target hydraulic parameter based on spatially exhaustive, but poorly resolved, measurements of a pertinent geophysical parameter and locally highly resolved, but spatially sparse, measurements of the considered geophysical and hydraulic parameters. To this end, my algorithm links the low- and high-resolution geophysical data via a downscaling procedure before relating the downscaled regional-scale geophysical data to the high-resolution hydraulic parameter field. I first illustrate the application of this novel data integration approach to a realistic synthetic database consisting of collocated high-resolution borehole measurements of the hydraulic and electrical conductivities and spatially exhaustive, low-resolution electrical conductivity estimates obtained from electrical resistivity tomography (ERT). The overall viability of this method is tested and verified by performing and comparing flow and transport simulations through the original and simulated hydraulic conductivity fields. The corresponding results indicate that the proposed data integration procedure does indeed allow for obtaining faithful estimates of the larger-scale hydraulic conductivity structure and reliable predictions of the transport characteristics over medium- to regional-scale distances. The approach is then applied to a corresponding field scenario consisting of collocated high- resolution measurements of the electrical conductivity, as measured using a cone penetrometer testing (CPT) system, and the hydraulic conductivity, as estimated from electromagnetic flowmeter and slug test measurements, in combination with spatially exhaustive low-resolution electrical conductivity estimates obtained from surface-based electrical resistivity tomography (ERT). The corresponding results indicate that the newly developed data integration approach is indeed capable of adequately capturing both the small-scale heterogeneity as well as the larger-scale trend of the prevailing hydraulic conductivity field. The results also indicate that this novel data integration approach is remarkably flexible and robust and hence can be expected to be applicable to a wide range of geophysical and hydrological data at all scale ranges. In the second part of my thesis, I evaluate in detail the viability of sequential geostatistical resampling as a proposal mechanism for Markov Chain Monte Carlo (MCMC) methods applied to high-dimensional geophysical and hydrological inverse problems in order to allow for a more accurate and realistic quantification of the uncertainty associated with the thus inferred models. Focusing on a series of pertinent crosshole georadar tomographic examples, I investigated two classes of geostatistical resampling strategies with regard to their ability to efficiently and accurately generate independent realizations from the Bayesian posterior distribution. The corresponding results indicate that, despite its popularity, sequential resampling is rather inefficient at drawing independent posterior samples for realistic synthetic case studies, notably for the practically common and important scenario of pronounced spatial correlation between model parameters. To address this issue, I have developed a new gradual-deformation-based perturbation approach, which is flexible with regard to the number of model parameters as well as the perturbation strength. Compared to sequential resampling, this newly proposed approach was proven to be highly effective in decreasing the number of iterations required for drawing independent samples from the Bayesian posterior distribution.

Multiple-scale hydrological and geophysical data integration through non-linear Bayesian sequential simulation

Significant progress has been made with regard to the quantitative integration of geophysical and hydrological data at the local scale. However, extending the corresponding approaches to the scale of a field site represents a major, and as-of-yet largely unresolved, challenge. To address this problem, we have developed downscaling procedure based on a non-linear Bayesian sequential simulation approach. The main objective of this algorithm is to estimate the value of the sparsely sampled hydraulic conductivity at non-sampled locations based on its relation to the electrical conductivity logged at collocated wells and surface resistivity measurements, which are available throughout the studied site. The in situ relationship between the hydraulic and electrical conductivities is described through a non-parametric multivariatekernel density function. Then a stochastic integration of low-resolution, large-scale electrical resistivity tomography (ERT) data in combination with high-resolution, local-scale downhole measurements of the hydraulic and electrical conductivities is applied. The overall viability of this downscaling approach is tested and validated by comparing flow and transport simulation through the original and the upscaled hydraulic conductivity fields. Our results indicate that the proposed procedure allows obtaining remarkably faithful estimates of the regional-scale hydraulic conductivity structure and correspondingly reliable predictions of the transport characteristics over relatively long distances.