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Fractures are a common comorbidity in children with the neural tube defect (NTD) spina bifida. Mutations in the Wnt/planar cell polarity (PCP) pathway contribute to NTDs in humans and mice, but whether this pathway independently determines bone mass is poorly understood. Here, we first confirmed that core Wnt/PCP components are expressed in osteoblasts and osteoclasts in vitro. In vivo, we performed detailed µCT comparisons of bone structure in tibiae from young male mice heterozygous for NTD-associated mutations versus WT littermates. PCP signalling disruption caused by Vangl2 (Vangl2Lp/+) or Celsr1 (Celsr1Crsh/+) mutations significantly reduced trabecular bone mass and distal tibial cortical thickness. NTD-associated mutations in non-PCP transcription factors were also investigated. Pax3 mutation (Pax3Sp2H/+) had minimal effects on bone mass. Zic2 mutation (Zic2Ku/+) significantly altered the position of the tibia/fibula junction and diminished cortical bone in the proximal tibia. Beyond these genes, we bioinformatically documented the known extent of shared genetic networks between NTDs and bone properties. 46 genes involved in neural tube closure are annotated with bone-related ontologies. These findings document shared genetic networks between spina bifida risk and bone structure, including PCP components and Zic2. Genetic variants which predispose to spina bifida may therefore independently diminish bone mass.

Objective: To project the prevalence of obesity across the WHO European region and examine whether the WHO target of halting obesity at 2010 levels by 2025 is achievable. Methods: BMI data were collected from online databases and the literature. Past and present BMI trends were extrapolated to 2025 using a non-linear categorical regression model fitted to nationally representative survey data. Where only 1 year of data was available, a flat trend was assumed. Where no data were available, proxy country data was used adjusted for demographics. Results: By 2025, obesity is projected to increase in 44 countries. If present trends continue, 33 of the 53 countries are projected to have an obesity prevalence of 20% or more. The highest prevalence is projected for Ireland (43%, 95% confidence interval (CI): 28-58%). Lithuania, Finland, and the Netherlands were each estimated to have an absolute increase of 2 percentage points in the prevalence of obesity between 2015 and 2025. Discussion: The quality of BMI data across Europe is highly variable, with fewer than 50% of the 53 countries having measured nationally representative data and often not enough data to interpret projections meaningfully. Nevertheless, the prevalence of obesity in the European Region appears to be increasing in most countries and, with it, the health and economic burden of its associated diseases. This paints a concerning picture of the future burden of obesity-related noncommunicable diseases across the region. Greater and continued effort for the implementation of effective preventive policies and interventions is required from governments.

Summary There is an increasing policy commitment to address the avoidable burdens of unhealthy diet, overweight and obesity. However, to design effective policies, it is important to understand why people make unhealthy dietary choices. Research from behavioural economics suggests a critical role for time discounting, which describes how people's value of a reward, such as better health, decreases with delay to its receipt. We systematically reviewed the literature on the relationship of time discounting with unhealthy diets, overweight and obesity in Web of Science and PubMed. We identified 41 studies that met our inclusion criteria as they examined the association between time discount rates and (i) unhealthy food consumption; (ii) overweight and (iii) response to dietary and weight loss interventions. Nineteen out of 25 cross‐sectional studies found time discount rates positively associated with overweight, obesity and unhealthy diets. Experimental studies indicated that lower time discounting was associated with greater weight loss. Findings varied by how time discount rates were measured; stronger results were observed for food than monetary‐based measurements. Network co‐citation analysis revealed a concentration of research in nutrition journals. Overall, there is moderate evidence that high time discounting is a significant risk factor for unhealthy diets, overweight and obesity and may serve as an important target for intervention. © 2016 The Authors Obesity Reviews published by John Wiley & Sons Ltd on behalf of International Association for the Study of Obesity (IASO)

INTRODUCTION AND OBJECTIVES Intracavernosal injection (ICI) of vasoactive agents has been successfully used in the treatment of erectile dysfunction (ED). The authors' pharmacologic erection program, using a fixed combination of prostaglandin E1 (PGE1) and papaverine, is notable for its simplicity and acceptance by patients who have suffered spinal cord injuries (SCIs). METHODS Patients undergo baseline questionnaire, physical examination, and hormone profile followed by instruction and injection of a fixed combination of PGE1 and papaverine. On successive visits, the patient injects himself and the dosage is titrated until a satisfactory erection is obtained. Patients who do not respond to injection of 1.0 cc are considered treatment failures. Patients return periodically for routine follow-up. RESULTS From May 1994 to March 1997, 37 patients with SCI underwent initial evaluation and 28 (76%) responded to injection therapy and were successfully using self-injection therapy at 3-month follow-up. Twenty-three patients are still on injection therapy. Five patients have dropped out for several reasons including a lack of a current sexual partner (60%) and pain with injection (40%). Patient age ranges from 24 to 72. The dosage range was 0.10 to 0.50 cc (mean = 0.29 cc). The average duration of erection was 43 minutes. At 3-month follow-up, 85% of the patients rated their erections as good or excellent. Forty-three percent of patients are using ICI 1 or more times per week. Seventy-seven percent of patients are moderately or extremely satisfied with their treatment and 89% said that they would recommend this program to a friend. CONCLUSIONS This simplified pharmacologic erection program offers safe, well accepted, and effective therapy for ED to a SCI population with very high patient satisfaction.

The leading priority for the Polish Presidency of the Council of the European Union was to reduce health inequalities across European societies, and, within its framework, prevention and control of respiratory diseases in children. This very important paper contain proposal of international cooperation on the prevention, early detection and monitoring of asthma and allergic diseases in childhood which will be undertaken by the EU member countries as a result of EU conclusion developed during the Polish Presidency of the Council of the European Union. This will result in collaboration in the field of chronic diseases, particularly respiratory diseases, together with the activity of the network of national institutions and NGOs in this area. Paper also contains extensive analysis of the socio-economic, political, epidemiological, technological and medical factors affecting the prevention and control of childhood asthma and allergy presented during Experts presidential conference organized in Warsaw-Ossa 21-22 September 2011. © 2012 John Wiley & Sons A/S.

The catchment area of Timis-Bega (13000 km²) is located on the western part of Romania. The orographical context, the Mediterranean climatic influence, the nature of the ground and the vegetation make that this relatively restricted geographical area has a rather great diversity of the flows. The latter is considered starting from 19 sub-basins, of a few km² to several hundred km². The annual mean discharge and low flow regionalizations of the Timis-Bega catchment was undertaken following similar work realised on the catchment area of the French Moselle (GALEA and CANALI, 2005). This work had shown the two-parameter Weibull distribution adequacy to describe the variability in time and space of the annual mean discharges and low flows of the sub-basins observed. Two principal results had been underlined, on the one hand the weak differentiation of the regional models established for annual mean discharges and the low flows, and on the other hand recommended use of episodic gauging of low flows to improve the regional models. Our intention is to check these preceding considerations, established on the French Moselle basin, in the hydro-climatic context of Timis-Bega. The results obtained make it to confirm as well the little differentiation between the regional models as the improvement of the regional models. More precisely, this improvement results from a better precision, than that obtained by traditional multiple regression, of the local discharge descriptor estimate, the median annual mean discharge or the median minimal daily low flow discharge. The use of low flow episodic discharge measurements, that are concomitant between the studied sub-basin and the reference sub-basin, allows the estimate of the median minimal daily low flow discharge and the median annual mean discharge in a fortuitous way. An explanation of this could be found in the observed weak differentiation between the regional annual mean discharge model and the regional average low flow discharge model for the average years to the dry ones. The interest of the low flow episodic measurements is sufficiently convincing to hold account of it in a later regionalization approach of the flow descriptors by geostatistical methods. Lastly, an unexpected result about the similarity of the regional distributions of the Moselle and Timis-Bega as well for the annual mean discharges or for the low flows. This result should be considered with prudence, it would abound towards the theory of the homogeneous hydrological regions.; Le bassin hydrographique du Timis-Bega, d'une superficie d'environ 13000 km², est situé à l'ouest de la Roumanie. Le contexte orographique, l'influence climatique méditerranéenne, la nature et l'occupation du sol font que cette zone géographique relativement restreinte présente une assez grande diversité des écoulements. Cette dernière est considérée à travers le choix de 19 sous-bassins, de quelques km² à plusieurs centaines de km². La régionalisation des modules et des débits d'étiage du Timis-Bega a été entreprise à la suite de travaux analogues réalisés sur le bassin hydrographique de la Moselle française (GALEA et CANALI, 2005). Ces travaux avaient montré l'adéquation de la loi de Weibull à 2 paramètres pour décrire la variabilité temporelle et spatiale des modules annuels et des étiages des sous-bassins observés. Deux principaux résultats avaient été soulignés, l'un concernait la faible différenciation des lois régionales établies pour les modules et les étiages des années moyenne à "sèches" (F£0,5), l'autre mettait l'accent sur l'usage de jaugeages épisodiques d'étiage pour améliorer la performance des modèles régionaux. Notre propos est de vérifier ces considérations précédentes, établies pour le bassin de la Moselle, dans le contexte hydro-climatique du Timis-Bega. Les résultats obtenus permettent de confirmer tant l'aspect peu différencié des lois régionales que l'aspect amélioration de la performance des modèles régionaux. Plus précisément, cette amélioration résulte d'une meilleure précision, que celle obtenue par régression multiple classique, de l'estimation du descripteur de régime local, le module annuel médian ou le débit journalier médian d'étiage qui représente une source d'incertitude importante du modèle régional respectif. L'usage d'une information épisodique sur les débits d'étiage, concomitante à un site étudié et à un sous-bassin de référence, permet l'estimation du débit journalier médian et par extension celle du module annuel médian. Une explication à cette extension pourrait être trouvée dans la faible différenciation des lois régionales pour les fréquences moyenne à "sèches". L'intérêt des jaugeages épisodiques d'étiage nous semble assez porteur pour être pris en considération lors d'une démarche ultérieure de régionalisation à bases géostatistiques des descripteurs de régime. Enfin, un résultat inattendu concerne la quasi similitude des lois régionales de la Moselle et du Timis-Bega tant pour ce qui concerne les modules annuels que les étiages. Ce résultat, à considérer avec prudence, abonderait dans le sens de la théorie des régions hydrologiques homogènes.

The characteristics of low flow, in Timis-Bega hydrographical area, are presented in this paper. The low flow analysis will be done using the flow-duration-frequency (QdF) modelling, establishing for each analyzed sub-basin a local modelling associated to a Weibull Law with two parameters. Local modelling requires the knowledge of two local descriptors: the characteristic times of the low flow De and the median value of annual daily minima quantils. Based on these models, a dimensionless regional model for low flow was established. On other hand, the theoretical distribution of mean annual discharges was drawn for each analysed sub-basin using also Weibull Law with two parameters. Theoretical distribution comparison of dimensionless regional models corresponding to low and mean flow shows that these are almost identical. Thus a low flow estimation for several durations and mean return periods was tested, based on mean flow characteristics. The utilization of this method to the ungauged sites supposes the knowledge of two parameters of Weibull regional distribution corresponding to annual mean discharges, as well as an estimation of two local descriptors of low flow based on the river basin characteristics.

National audience; The water needs for farming irrigation in the Tescou and Séoune sub-basins (Basin Adour-Garonne) have increased considerably over the past thirty years. The needs were met, in part, by the creation of numerous reservoirs. For the Tescou catchment, with rapid but small-volume floods, we have 184 individual reservoirs with an accumulated theoretical volume of 4.3 Mm3, which intercept about a third (92 km²) of its surface (287 km²). For the Séoune catchment, the need for irrigation is a little less strong, considering its size (463 km²) and a water resource relatively more abundant. Close to 160 reservoirs can be counted, with a theoretical storage volume of 6.5 Mm3 for an intercepted surface of about a quarter of the sub-basin (122 km²). Hydrological monitoring data are available in the form of an influenced time series Q(t) with a period of observation of about 30 years for each sub-basin. From the observed discharges, our objective was to identify and to quantify anthropogenic impacts on three components of the hydrological regime: floods, annual mean discharge and low-flows. The seasonal approach of floods and annual mean discharges permitted a differentiation of the anthropogenic impact according to the "winter" (months 12 to 6) and "summer" (months 7 to 11) seasons. This approach reflects the present management of water in these agricultural sub-basins: storage in winter and irrigation during the first months of summer. To identify the impact, we used tests to detect stationnarity breaks in the time series: LANG for floods and an adaptation of BOIS for annual mean discharges and low-flows. For summer floods and summer annual mean discharges, the tests showed that the time series were stationary during the period of observation. For winter floods and winter annual mean discharges the tests showed stationnarity breaks in the time series, which allowed us to define the stationary sub-periods. These sub-periods were consistent with the evolution of the accumulated theoretical withdrawals during the last thirty years. The same analysis of stationnarity breaks made on flows was also done on rainfall to strengthen our results. The stationnarity of the rainfall observed over the time series shows that there is not a climatic component; in other words, the trends detected in the streamflow record are essentially of anthropogenic origin. The test shows any impact of possible pumpings of the low-flow and especially for the VCN30 norm (minimum annual mean flow on 30 consecutive days) for both sub-basins. Finally, the use of water for irrigation essentially affects winter floods and annual mean discharges. A test to quantify this trend was carried out with a statistical analysis associating the observations of each stationary sub-period and the discharges simulated for a similar rainfall. From the resulting statistical models and the curves of pressure of theoretical irrigation requirements, we deduced a probable trend for the quantiles of winter floods and mean annual winter discharges. In a general way, winter floods in both sub-basins were strongly reduced in peak and volume by the set of the small reservoirs. The impact observed on the flood quantiles remains coherent in relation to the theoretical withdrawal volumes referenced above. The reservoirs are without significant action on the transfer time (approximately 19 days) in the Séoune sub-basin, where the floods are voluminous. On the other hand, for the Tescou sub-basin, with rapid and small-volume floods, the time of transfer increases considerably (8 h) between the state of zero withdrawal (natural: 1.73 days) and the present state close to 6 Mm3 (2.07 days). Concerning winter annual mean discharge in both sub-basins, the winter mean runoff coefficient decreased 31% and 42%, for the Séoune and Tescou sub-basins respectively, between the natural state and the present state. This reduction of the runoff coefficients does not correspond to the theoretical volumes stocked in the reservoirs. In other words, the theoretical volumes of the reservoirs cannot completely explain the observed strong reduction of the runoff coefficients. However, the consistency of the various controls, so much on the observed time series that on the done models, incite us to validate these results. These results should be taken into consideration in water management, if the climatic conditions and soil occupation don't change.; Les besoins en eau pour l'irrigation des cultures des sous-bassins du Tescou et de la Séoune (Bassin Adour-Garonne) se sont considérablement accrus ces trente dernières années. Cela s'est manifesté, entre autres, par la création de très nombreuses retenues collinaires. Pour le sous-bassin du Tescou, aux crues rapides et peu volumineuses, on totalise 184 retenues individuelles dont le volume théorique cumulé s'élève à 4,3 Mm3 et qui interceptent environ un tiers (92 km²) de sa superficie (287 km²). Pour la Séoune, la pression due à l'usage de l'eau pour l'irrigation est un peu moins forte, compte tenu de sa taille (463 km²) et d'une ressource en eau relativement plus abondante. Près de 160 retenues collinaires sont dénombrées, elle représentent un volume de stockage théorique de 6,5 Mm3 pour une superficie interceptée d'environ un quart du sous-bassin (122 km²). Le suivi hydrométrique des sous-bassins permet de disposer pour chacun d'eux d'une chronique de débit influencée Q(t) sur une période d'observation d'environ 30 ans. A partir des débits observés, notre objectif a été d'identifier et de quantifier l'impact anthropique pour trois composantes du régime hydrologique : crue, module et étiage. L'approche saisonnière des crues et modules a permis une différenciation de l'impact anthropique selon les saisons "hiver" (mois 12 à 6) et "été" (mois 7 à 11). Cette saisonnalisation hydrologique reflète bien le mode de gestion actuel de la ressource en eau de ces sous-bassins agricoles : stockage l'hiver et irrigation à partir des retenues collinaires durant les premiers mois d'été. Pour identifier l'impact, nous avons fait usage de tests de détection de rupture de stationnarité des chroniques hydrologiques : de LANG (2004) pour les crues et d'une adaptation du test de BOIS (1986) pour les modules et étiages des sous-bassins. Pour ce qui concerne les crues d'été et les modules d'été les tests montrent que les chroniques sont stationnaires sur l'ensemble de la période d'observation. Pour les crues et les modules d'hiver par contre, les tests relèvent des ruptures de stationnarité des chroniques qui vont nous permettre de définir des sous-périodes stationnaires. Ces sous-périodes sont sensiblement cohérentes avec l'évolution des prélèvements théoriques cumulés de ces trente dernières années. L'analyse des ruptures de stationnarité menée sur les débits a été de même effectuée sur les pluies pour consolider nos résultats. La stationnarité des chroniques de pluie observées montre qu'il n'y a pas de composante climatique, autrement dit que la tendance détectée sur les débits est essentiellement d'origine anthropique. Le test statistique de BOIS ne révèle aucun impact des éventuels pompages sur les débits d'étiage et tout particulièrement pour ce qui concerne la norme VCN30 "débit moyen minimum annuel sur 30 jours consécutifs" des deux sous-bassins. Finalement, l'usage de l'eau pour l'irrigation affecte essentiellement les crues et les modules de la saison hiver. Un essai de quantification de cette tendance a été mené à partir d'une analyse statistique associant les observations des sous-périodes stationnaires et les débits simulés pour une même référence pluviométrique. A partir des modélisations statistiques réalisées et des courbes de pression des besoins théoriques de l'irrigation, nous en avons déduit une tendance vraisemblable sur les quantiles de crue et les modules d'hiver. De manière générale, les crues de la saison hiver des deux sous-bassins sont fortement réduites en pointe et volume par l'ensemble des petites retenues. L'impact observé sur les quantiles de crue reste cohérent par rapport aux volumes théoriques prélevés dernièrement référencés. Les retenues collinaires sont sans action significative sur le temps de transfert (19j environ) du sous-bassin de la Séoune dont les crues sont volumineuses. Pour le Tescou par contre, aux crues rapides et peu volumineuses, le temps de transfert augmente sensiblement de 8h entre l'état de prélèvement zéro ("naturel" : 1,73j) et l'état actuel proche de 6 Mm3 (2,07j). Pour ce qui concerne les modules d'hiver des sous-bassins de la Séoune et du Tescou le coefficient d'écoulement moyen d'hiver diminue respectivement de 31% en moyenne et de 42% en moyenne entre l'état "naturel" et l'état anthropisé actuel. Cette diminution des coefficients d'écoulement est sans commune mesure avec les volumes théoriques stockés à partir des retenues collinaires. Autrement dit, les volumes théoriques des retenues collinaires ne peuvent expliquer à eux seuls la forte diminution des coefficients d'écoulement observés. Cependant, la cohérence des divers contrôles effectués, tant sur les chroniques observées que sur les modélisations effectuées, nous incitent à valider ces résultats. Ceux-ci devraient être retenus pour des objectifs de gestion immédiats ou ultérieurs de la ressource, si les conditions climatiques et d'occupation du sol n'évoluent guère.

A flow-duration-frequency regionalisation is carried out on the Timis and Bega drainage basins in the west of Romania. This regionalisation concerns 28 sub-basins having about thirty years of streamflow measurements (daily flow, instantaneous flood peaks and hydrographs). This work about the floods regionalisation is realized in the framework of the Riverlife European project. The regional model will allow defining the hydrographs of the project necessary for the hydraulic modelling. This hydraulic project is necessary for protecting Timişoara - city against the floods. The method uses the hypotheses of the converging QdF model and adapts the index flood method for obtaining a regional dimensionless distribution. For long return periods, this approach uses the GRADEX method, which extrapolates discharge distributions according to the rainfall distributions.The dimensionless regional QdF model needs two local descriptors of target site to be denormed: QIXA10 and Δ: the annual maximum instantaneous flow with a 10% probability to be exceeded (the 10-year peak flood) and a characteristic duration, respectively. For these both variables, the relations obtained by regression are presented, involving morphologic and climatic basin characteristics., Une régionalisation débit-durée-fréquence a été menée sur les bassins hydrographiques du Timi et du Béga à l`ouest de la Roumanie. Elle a concerné 28 sous-bassins dont les chroniques d`observation d`environ 30 ans concernent essentiellement les débits quotidiens, les débits de pointes et quelques hydrogrammes des crues les plus importantes. Ce travail de régionalisation des régimes de crue est réalisé dans le cadre du projet européen Riverlife. Le modèle régional établi permettra de définir les hydrogrammes de projet nécessaires à la modélisation hydraulique. L`enjeu de l`étude hydraulique est de protéger la ville de Timisoara contre les inondations. La méthode utilise les hypothèses de convergence du modèle QdF et la méthode de l`indice de crue est adaptée pour définir la loi régionale. L`utilisation du modèle QdF régional sur un site quelconque nécessite de connaître deux descripteurs locaux du régime des crues : le débit de pointe décennal QIXA10 et la durée caractéristique de crue D. Pour ces deux descripteurs, les régressions établies en fonction des caractéristiques morpho-climatiques sont présentées.