Novel associations for hypothyroidism include known autoimmune risk loci

Hypothyroidism is the most common thyroid disorder, affecting about 5% of the general population. Here we present the first large genome-wide association study of hypothyroidism, in 2,564 cases and 24,448 controls from the customer base of 23andMe, Inc., a personal genetics company. We identify four genome-wide significant associations, two of which are well known to be involved with a large spectrum of autoimmune diseases: rs6679677 near _PTPN22_ and rs3184504 in _SH2B3_ (p-values 3.5e-13 and 3.0e-11, respectively). We also report associations with rs4915077 near _VAV3_ (p-value 8.3e-11), another gene involved in immune function, and rs965513 near _FOXE1_ (p-value 3.1e-14). Of these, the association with _PTPN22_ confirms a recent small candidate gene study, and _FOXE1_ was previously known to be associated with thyroid-stimulating hormone (TSH) levels. Although _SH2B3_ has been previously linked with a number of autoimmune diseases, this is the first report of its association with thyroid disease. The _VAV3_ association is novel. These results suggest heterogeneity in the genetic etiology of hypothyroidism, implicating genes involved in both autoimmune disorders and thyroid function. Using a genetic risk profile score based on the top association from each of the four genome-wide significant regions in our study, the relative risk between the highest and lowest deciles of genetic risk is 2.1

Exploring the evidence base for national and regional policy interventions to combat resistance

The effectiveness of existing policies to control antimicrobial resistance is not yet fully understood. A strengthened evidence base is needed to inform effective policy interventions across countries with different income levels and the human health and animal sectors. We examine three policy domains—responsible use, surveillance, and infection prevention and control—and consider which will be the most effective at national and regional levels. Many complexities exist in the implementation of such policies across sectors and in varying political and regulatory environments. Therefore, we make recommendations for policy action, calling for comprehensive policy assessments, using standardised frameworks, of cost-effectiveness and generalisability. Such assessments are especially important in low-income and middle-income countries, and in the animal and environmental sectors. We also advocate a One Health approach that will enable the development of sensitive policies, accommodating the needs of each sector involved, and addressing concerns of specific countries and regions

Emissions of transboundary air pollutants in the Netherlands 1990-2012 : Informative Inventory Report 2014

Emissies Nederland blijven in 2012 onder nationale plafonds De uitstoot van stikstofoxiden (NOx), ammoniak, zwaveldioxide en niet-methaan vluchtige organische stoffen (NMVOS) is in 2012 in Nederland licht gedaald. Daarmee bleef de uitstoot onder de maxima die de Europese Unie daaraan sinds 2010 stelt. Nederland voldoet daardoor, net als in 2011, aan de vier 'nationale emissieplafonds' (NEC) voor deze stoffen. Dit blijkt uit de Nederlandse emissiecijfers van grootschalige luchtverontreinigende stoffen. Het RIVM verzamelt en analyseert deze cijfers. Behalve bovengenoemde stoffen gaat het om de uitstoot van koolmonoxide, fijn stof (PM10), zware metalen en persistente organische stoffen (POP's). De uitstoot van al deze stoffen is tussen 1990 en 2012 gedaald. Dit komt vooral door schonere auto's en brandstoffen en door emissiebeperkende maatregelen van industriële sectoren. Meer kilometers door bromfietsen Door de jaren heen zijn de methoden om de emissies te berekenen verbeterd, wat nu resulteert in nauwkeurigere cijfers. De emissies van bromfietsen en motorfietsen zijn afhankelijk van het aantal gereden kilometers per jaar en daar is nu beter inzicht in. Het totale aantal gereden kilometers door bromfietsen blijkt in de afgelopen jaren bijna twee keer zo hoog is als werd gedacht. Daarmee is de uitstoot van schadelijke stoffen navenant hoger. Ten opzichte van andere typ voertuigen blijven bromfietsen echter een relatief kleine emissiebron en dragen ze beperkt bij aan de totale nationale emissies. In steden zijn ze wel een relevante bron. Het aantal gereden kilometers door motorfietsen, en daarmee de uitstoot, blijft in lijn met eerdere inzichten. Vrachtauto's zwaarder beladen De uitstoot van schadelijke stoffen door vrachtauto's is voor het eerst berekend op basis van recente inzichten in het gewicht van vrachtauto's. Trekker-opleggers blijken zwaarder beladen dan tot nu toe werd verondersteld. Ook rijden vrachtauto's vaker met een aanhanger dan tot nu toe werd aangenomen, waardoor ze zwaarder zijn. Een hoger gewicht betekent een hoger brandstofverbruik, en veelal ook een hogere uitstoot per gereden kilometer. De uitstoot van PM10 door vrachtauto's is hierdoor circa 5 procent hoger dan in de vorige IIR-rapportage. Hogere emissies ammoniak De uitstoot van ammoniak blijkt hoger dan eerder werd verondersteld vanwege enkele nieuwe inzichten; de cijfers zijn hierdoor vanaf 1997 bijgesteld. Zo worden luchtwassers, die voornamelijk op varkensstallen zitten, niet altijd gebruikt. Ook is vanaf 2002 in melkveestallen het leefoppervlak per dier toegenomen. Door het grotere contactoppervlak van mest met lucht wordt meer ammoniak uitgestoten. Door de aangepaste aannames is het nationale totaal met 6,6 kiloton verhoogd ten opzichte van 2011.Emissions the Netherlands in 2012 remain under national ceilings Emissions of nitrogen oxides (NOx), ammonia, sulphur dioxide and non-methane volatile organic compounds (NMVOC) in the Netherlands have slightly decreased in 2012. Consequently, the emissions stayed below the caps the European Union has set from 2010. Herewith, the Netherlands comply with all four so-called emission ceilings (NEC). This has become apparent from the emission data on air pollutants from the Netherlands. RIVM collects and reports these data. Besides above-mentioned substances, emissions of carbon monoxide, particulate matter (PM10), heavy metals and persistent organic pollutants (POPs) have been reported. The emissions of all substances have decreased in the 1990 - 2012 period. The downward trend may in particular be attributed to cleaner fuels, cleaner car engines and to emission reductions in the industrial sectors. More kilometres by mopeds Over the years emission calculation methods have been improved, resulting in higher data accuracy. In 2012, the emissions from mopeds and motorcycles have been calculated, based on improved knowledge of the mileages. The total number of kilometres driven by mopeds appears to have been nearly twice as high in recent years. As a result, the emissions of pollutants are proportionally higher. In relation to the total number of vehicles, the number of mopeds however remains relatively low and their contribution to the total national emissions is limited. In cities, they are a relevant source. The mileages by motorcycles, and consequently their emissions remain in line with previous insights. Heavy-duty vehicles carry heavier loads Emissions of pollutants by heavy-duty trucks have for the first time been calculated on the basis of recent insights in truck loads. Tractor-trailer combinations appear to carry heavier loads and the fraction of trailers behind rigid trucks is larger than previously assumed. A heavier load means a higher fuel use and for most substances a higher emission per kilometre driven. PM10 emissions by heavy-duty trucks are about 5 percent higher than in the previous IIR report. Higher agricultural ammonia emissions Agricultural ammonia emissions appear to be higher than previously assumed because of new insights. Air scrubbers on animal housing (predominantly pigs) were not always in use or even employed. Since 2002, the living space per animal has increased for dairy cattle housing. This resulted in a higher contact surface manure-air and thus more ammonia emitted. The new insights have raised the national total of ammonia emissions by about 6 percent compared to 2011

Potentiation of thrombus instability: a contributory mechanism to the effectiveness of antithrombotic medications

© The Author(s) 2018The stability of an arterial thrombus, determined by its structure and ability to resist endogenous fibrinolysis, is a major determinant of the extent of infarction that results from coronary or cerebrovascular thrombosis. There is ample evidence from both laboratory and clinical studies to suggest that in addition to inhibiting platelet aggregation, antithrombotic medications have shear-dependent effects, potentiating thrombus fragility and/or enhancing endogenous fibrinolysis. Such shear-dependent effects, potentiating the fragility of the growing thrombus and/or enhancing endogenous thrombolytic activity, likely contribute to the clinical effectiveness of such medications. It is not clear how much these effects relate to the measured inhibition of platelet aggregation in response to specific agonists. These effects are observable only with techniques that subject the growing thrombus to arterial flow and shear conditions. The effects of antithrombotic medications on thrombus stability and ways of assessing this are reviewed herein, and it is proposed that thrombus stability could become a new target for pharmacological intervention.Peer reviewedFinal Published versio

Silicon Mie Resonators for Highly Directional Light Emission from monolayer MoS2

Controlling light emission from quantum emitters has important applications ranging from solid-state lighting and displays to nanoscale single-photon sources. Optical antennas have emerged as promising tools to achieve such control right at the location of the emitter, without the need for bulky, external optics. Semiconductor nanoantennas are particularly practical for this purpose because simple geometries, such as wires and spheres, support multiple, degenerate optical resonances. Here, we start by modifying Mie scattering theory developed for plane wave illumination to describe scattering of dipole emission. We then use this theory and experiments to demonstrate several pathways to achieve control over the directionality, polarization state, and spectral emission that rely on a coherent coupling of an emitting dipole to optical resonances of a Si nanowire. A forward-to-backward ratio of 20 was demonstrated for the electric dipole emission at 680 nm from a monolayer MoS2 by optically coupling it to a Si nanowire

From chaos to order: Chain-length dependence of the free energy of formation of meso-tetraalkylporphyrin self-assembled monolayer polymorphs

© 2016 American Chemical Society. We demonstrate that systematic errors can be reduced and physical insight gained through investigation of the dependence of free energies for meso-tetraalkylporphyrin self-assembled monolayers (SAMs) polymorphism on the alkyl chain length m. These SAMs form on highly ordered pyrolytic graphite (HOPG) from organic solution, displaying manifold densities and atomic structures. SAMs with m = 11-19 are investigated experimentally while those with m = 6-28 are simulated using density-functional theory (DFT). It is shown that, for m = 15 or more, the alkyl chains crystallize to dominate SAM structure. Meso-tetraalkylporphyrin SAMs of length less than 11 have never been observed, a presumed effect of inadequate surface attraction. Instead, we show that free energies of SAM formation actually enhance as the chain length decreases. The inability to image regular SAMs stems from the appearance of many polymorphic forms of similar free energy, preventing SAM ordering. We also demonstrate a significant odd/even effect in SAM structure arising from packing anomalies. Comparison of the chain-length dependence of formation free energies allows the critical dispersion interactions between molecules, solvent, and substrate to be directly examined. Interpretation of the STM data combined with measured enthalpies indicates that Grimme's D3 explicit-dispersion correction and the implicit solvent correction of Floris, Tomasi and Pascual Ahuir are both quantitatively accurate and very well balanced to each other

Comparing nuclear power trajectories in Germany and the UK: from ‘regimes' to ‘democracies’ in sociotechnical transitions and Discontinuities

This paper focuses on arguably the single most striking contrast in contemporary major energy politics in Europe (and even the developed world as a whole): the starkly differing civil nuclear policies of Germany and the UK. Germany is seeking entirely to phase out nuclear power by 2022. Yet the UK advocates a ‘nuclear renaissance’, promoting the most ambitious new nuclear construction programme in Western Europe.Here,this paper poses a simple yet quite fundamental question: what are the particular divergent conditions most strongly implicated in the contrasting developments in these two countries. With nuclear playing such an iconic role in historical discussions over technological continuity and transformation, answering this may assist in wider understandings of sociotechnical incumbency and discontinuity in the burgeoning field of‘sustainability transitions’. To this end, an ‘abductive’ approach is taken: deploying nine potentially relevant criteria for understanding the different directions pursued in Germany and the UK. Together constituted by 30 parameters spanning literatures related to socio-technical regimes in general as well as nuclear technology in particular, the criteria are divided into those that are ‘internal’ and ‘external’ to the ‘focal regime configuration’ of nuclear power and associated ‘challenger technologies’ like renewables. It is ‘internal’ criteria that are emphasised in conventional sociotechnical regime theory, with ‘external’ criteria relatively less well explored. Asking under each criterion whether attempted discontinuation of nuclear power would be more likely in Germany or the UK, a clear picture emerges. ‘Internal’ criteria suggest attempted nuclear discontinuation should be more likely in the UK than in Germany– the reverse of what is occurring. ‘External’ criteria are more aligned with observed dynamics –especially those relating to military nuclear commitments and broader ‘qualities of democracy’. Despite many differences of framing concerning exactly what constitutes ‘democracy’, a rich political science literature on this point is unanimous in characterising Germany more positively than the UK. Although based only on a single case,a potentially important question is nonetheless raised as to whether sociotechnical regime theory might usefully give greater attention to the general importance of various aspects of democracy in constituting conditions for significant technological discontinuities and transformations. If so, the policy implications are significant. A number of important areas are identified for future research, including the roles of diverse understandings and specific aspects of democracy and the particular relevance of military nuclear commitments– whose under-discussion in civil nuclear policy literatures raises its own questions of democratic accountability