Positive predictive values for detection of trisomies 21, 18 and 13 and termination of pregnancy rates after referral for advanced maternal age, first trimester combined test or ultrasound abnormalities in a national screening programme (2007-2009)

Objective: The objective of this article is to analyse the positive predictive value (PPV) of trisomies 21, 18 and 13 after referral for advanced maternal age (AMA), first trimester combined test or ultrasound findings to suggest improvements for clinical practice. Methods: Data (48457 combined tests, 134000 fetal anomaly scans and 24379 invasive prenatal tests) were combined to calculate PPV and termination of pregnancy rates. Results: For referral for AMA, the PPV for T21 was 1.0% and 1.8% for amniocentesis and chorionic villus biopsy, respectively; for the combined test at a maternal age ≥36years, these percentages were 4.9% and 12.5%, respectively and for maternal age 90% unless detected after referral for ultrasound findings (71.5-85.9%). About 50% of pregnant women with a high combined test risk chose not to have invasive testing. Conclusions: Advanced MA is still a large contributor to invasive testing but should be abandoned (low PPV, high fetal loss rate) and be replaced by reimbursable combined test screening for all women. Patient information on second trimester ultrasound screening should indicate that abnormal ultrasound findings are associated with high trisomy rate

Subcellular localization of MC4R with ADCY3 at neuronal primary cilia underlies a common pathway for genetic predisposition to obesity.

Most monogenic cases of obesity in humans have been linked to mutations in genes encoding members of the leptin-melanocortin pathway. Specifically, mutations in MC4R, the melanocortin-4 receptor gene, account for 3-5% of all severe obesity cases in humans1-3. Recently, ADCY3 (adenylyl cyclase 3) gene mutations have been implicated in obesity4,5. ADCY3 localizes to the primary cilia of neurons 6 , organelles that function as hubs for select signaling pathways. Mutations that disrupt the functions of primary cilia cause ciliopathies, rare recessive pleiotropic diseases in which obesity is a cardinal manifestation 7 . We demonstrate that MC4R colocalizes with ADCY3 at the primary cilia of a subset of hypothalamic neurons, that obesity-associated MC4R mutations impair ciliary localization and that inhibition of adenylyl cyclase signaling at the primary cilia of these neurons increases body weight. These data suggest that impaired signaling from the primary cilia of MC4R neurons is a common pathway underlying genetic causes of obesity in humans

Achieving autonomic Web service compositions with models at runtime

[EN] Several exceptional situations may arise in the complex, heterogeneous, and changing contexts where Web service operations run. For instance, a Web service operation may have greatly increased its execution time or may have become unavailable. The contribution of this article is to provide a tool-supported framework to guide autonomic adjustments of context-aware service compositions using models at runtime. During execution, when problematic events arise in the context, models are used by an autonomic architecture to guide changes of the service composition. Under the closed-world assumption, the possible context events are fully known at design time. Nevertheless, it is difficult to foresee all the possible situations arising in uncertain contexts where service compositions run. Therefore, the proposed framework also covers the dynamic evolution of service compositions to deal with unexpected events in the open world. An evaluation demonstrates that our framework is efficient during dynamic adjustments.Alférez-Salinas, GH.; Pelechano Ferragud, V. (2017). Achieving autonomic Web service compositions with models at runtime. Computers & Electrical Engineering. 63:332-352. doi:10.1016/j.compeleceng.2017.08.004S3323526

Impact of obesity on taste receptor expression in extra-oral tissues: emphasis on hypothalamus and brainstem OPEN

Sweet perception promotes food intake, whereas that of bitterness is inhibitory. Surprisingly, the expression of sweet G protein-coupled taste receptor (GPCTR) subunits (T1R2 and T1R3) and bitter GPCTRs (T2R116, T2R118, T2R138 and T2R104), as well as the α-subunits of the associated signalling complex (αGustducin, Gα14 and αTransducin), in oral and extra-oral tissues from lean and obese mice, remains poorly characterized. We focused on the impact of obesity on taste receptor expression in brain areas involved in energy homeostasis, namely the hypothalamus and brainstem. We demonstrate that many of the GPCTRs and α-subunits are co-expressed in these tissues and that obesity decreases expression of T1R3, T2R116, Gα14, αTrans and TRPM5. In vitro high levels of glucose caused a prominent down-regulation of T1R2 and Gα14 expression in cultured hypothalamic neuronal cells, leptin caused a transient down-regulation of T1R2 and T1R3 expression. Intriguingly, expression differences were also observed in other extra-oral tissues of lean and obese mice, most strikingly in the duodenum where obesity reduced the expression of most bitter and sweet receptors. In conclusion, obesity influences components of sweet and bitter taste sensing in the duodenum as well as regions of the mouse brain involved in energy homeostasis, including hypothalamus and brainstem. Taste perception is an important aspect in the control of food intake. Taste is mainly sensed by taste receptor containing cells located in the taste buds distributed in the different gustatory epitheliums in the tongue, palate, larynx and epiglottis. The sensing of sweet, umami and bitter taste is mediated by two G protein-coupled taste receptor (GPCTR) families: the T1R family, which is mainly involved in the sensing of sweet and umami taste-like signalling molecules and the T2R family, involved in the sensing of bitter taste-like signalling molecules 1 . The T1R family consists of three different GPCTRs that generate at least two heterodimeric receptors: T1R1+T1R3 associated with umami taste sensing and T1R2+T1R3 associated with sweet taste sensing 1,2 . In mice the T2R family consists of at least 36 distinct taste receptor members, which individually sense bitter taste like molecules 3 . The human T2R16 selectively recognizes β-glucopyranosides 4 , while the human T2R38 recognizes phenylthiocarbamide (PTC) 5 . The functional importance of the latter two human receptors was demonstrated by the finding that overexpression of either receptor in mice increases food avoidance 6 . Although the T1R and T2R receptor families drive different taste perceptions, they share similar downstream G protein-coupled signalling pathways. In particular, the taste specific α-subunit of the G protein α-gustducin (αGust) is coupled to both receptor families and has been described as critical for sweet and bitter taste responses 7 . Nevertheless, αGust knockout animals still preserve a moderate sensitivity to some bitter compounds and to sweet compounds in higher mM concentration

Serotonin controlling feeding and satiety

Serotonin has been implicated in the control of satiety for almost four decades. Historically, the insight that the appetite suppressant effect of fenfluramine is linked to serotonin has stimulated interest in and research into the role of this neurotransmitter in satiety. Various rodent models, including transgenic models, have been developed to identify the involved 5-HT receptor subtypes. This approach also required the availability of receptor ligands of different selectivity, and behavioural techniques had to be developed simultaneously which allow differentiating between unspecific pharmacological effects of these ligands and ‘true’ satiation and satiety. Currently, 5-HT1B, 5-HT2C and 5-HT6 receptors have been identified to mediate serotonergic satiety in different ways. The recently approved anti-obesity drug lorcaserin is a 5-HT2C receptor agonist. In brain, both hypothalamic (arcuate nucleus, paraventricular nucleus) and extrahypothalamic sites (parabrachial nucleus, nucleus of the solitary tract) have been identified to mediate the serotonergic control of satiety. Serotonin interacts within the hypothalamus with endogenous orexigenic (Neuropeptide Y/Agouti related protein) and anorectic (α-melanocyte stimulating hormone) peptides. In the nucleus of the solitary tract serotonin integrates peripheral satiety signals. Here, the 5-HT3, but possibly also the 5-HT2C receptor play a role. It has been found that 5-HT acts in concert with such peripheral signals as cholecystokinin and leptin. Despite the recent advances of our knowledge, many of the complex interactions between 5-HT and other satiety factors are not fully understood yet. Further progress in research will also advance the development of new serotonergic anti-obesity drugs

Explaining variation in Down's syndrome screening uptake: comparing the Netherlands with England and Denmark using documentary analysis and expert stakeholder interviews.

Background: The offer of prenatal Down’s syndrome screening is part of routine antenatal care in most of Europe; however screening uptake varies significantly across countries. Although a decision to accept or reject screening is a personal choice, it is unlikely that the widely differing uptake rates across countries can be explained by variation in individual values alone. The aim of this study was to compare Down’s syndrome screening policies and programmes in the Netherlands, where uptake is relatively low ( 90% respectively), in an attempt to explain the observed variation in national uptake rates. Methods: We used a mixed methods approach with an embedded design: a) documentary analysis and b) expert stakeholder analysis. National central statistical offices and legal documents were studied first to gain insight in demographic characteristics, cultural background, organization and structure of healthcare followed by documentary analysis of primary and secondary sources on relevant documents on DSS policies and programme. To enhance interpretation of these findings we performed in-depth interviews with relevant expert stakeholders. Results: There were many similarities in the demographics, healthcare systems, government abortion legislation and Down’s syndrome screening policy across the studied countries. However, the additional cost for Down’s syndrome screening over and above standard antenatal care in the Netherlands and an emphasis on the ‘right not to know’ about screening in this country were identified as potential explanations for the ‘low’ uptake rates of Down’s syndrome screening in the Netherlands. The social context and positive framing of the offer at the service delivery level may play a role in the relatively high uptake rates in Denmark. Conclusions: This paper makes an important contribution to understanding how macro-level demographic, social and healthcare delivery factors may have an impact on national uptake rates for Down’s syndrome screening. It has suggested a number of policy level and system characteristics that may go some way to explaining the relatively low uptake rates of Down’s syndrome screening in the Netherlands when compared to England and Denmark

Output Prediction for non Demand-Driven Power Systems using Neural Networks

In the Dutch liberalized electricity market, parties involved in the use of the electricity network need to send their planned electricity activities to the national grid administrator each day in advance. When a market party creates imbalance by deviating from the planned activity, it has to pay imbalance costs. The output of non demand-driven power systems is irregular and depends on different stochastic factors. To minimize the producer's imbalance costs, the power output has to be accurately predicted.This thesis investigates the output prediction of non demand-driven power systems using neural networks. Models based on the multilayer perceptron neural network are used for this purpose. The results obtained when building models based on real-life data, as well as the simulation of the models in use are described. A detailed analysis of the influence of various parameters in neural network based modeling is given, like input relevance and the optimal division of one year for separate models.It is shown that ensembles of these neural networks are able to generalize from real-life dataand achieve a reasonably well performance in predicting the power output.

Ubikima: Ubiquitous authentication using a smartphone, migrating from passwords to strong cryptography

Contains fulltext : 120036.pdf (publisher's version ) (Open Access)CCS'13 2013 ACM SIGSAC Conference on Computer and Communications Security Berlin, Germany — November 04 - 08, 201