Geostatistical radar-raingauge combination with nonparametric correlograms: methodological considerations and application in Switzerland

Modelling spatial covariance is an essential part of all geostatistical methods. Traditionally, parametric semivariogram models are fit from available data. More recently, it has been suggested to use nonparametric correlograms obtained from spatially complete data fields. Here, both estimation techniques are compared. Nonparametric correlograms are shown to have a substantial negative bias. Nonetheless, when combined with the sample variance of the spatial field under consideration, they yield an estimate of the semivariogram that is unbiased for small lag distances. This justifies the use of this estimation technique in geostatistical applications. Various formulations of geostatistical combination (Kriging) methods are used here for the construction of hourly precipitation grids for Switzerland based on data from a sparse realtime network of raingauges and from a spatially complete radar composite. Two variants of Ordinary Kriging (OK) are used to interpolate the sparse gauge observations. In both OK variants, the radar data are only used to determine the semivariogram model. One variant relies on a traditional parametric semivariogram estimate, whereas the other variant uses the nonparametric correlogram. The variants are tested for three cases and the impact of the semivariogram model on the Kriging prediction is illustrated. For the three test cases, the method using nonparametric correlograms performs equally well or better than the traditional method, and at the same time offers great practical advantages. Furthermore, two variants of Kriging with external drift (KED) are tested, both of which use the radar data to estimate nonparametric correlograms, and as the external drift variable. The first KED variant has been used previously for geostatistical radar-raingauge merging in Catalonia (Spain). The second variant is newly proposed here and is an extension of the first. Both variants are evaluated for the three test cases as well as an extended evaluation period. It is found that both methods yield merged fields of better quality than the original radar field or fields obtained by OK of gauge data. The newly suggested KED formulation is shown to be beneficial, in particular in mountainous regions where the quality of the Swiss radar composite is comparatively low. An analysis of the Kriging variances shows that none of the methods tested here provides a satisfactory uncertainty estimate. A suitable variable transformation is expected to improve this

Efficacy, safety, and tolerability of adjunctive brivaracetam for secondarily generalized tonic-clonic seizures: Pooled results from three Phase III studies

AbstractPurposeSecondarily generalized tonic-clonic seizures (SGTCS) are among the most devastating types of seizures, contributing to increased morbidity and mortality. Brivaracetam (BRV), a selective, high-affinity ligand for synaptic vesicle 2A (SV2A), has been shown to be useful for the adjunctive treatment of focal seizures. We sought to determine its specific efficacy in treating SGTCS.MethodsData were pooled from three Phase III studies (NCT00490035; NCT00464269; NCT01261325) of adults with focal seizures taking 1⿿2 antiepileptic drugs (AEDs) who received placebo or BRV 50⿿200mg/day without titration over a 12-week treatment period. We report efficacy and safety/tolerability data for the BRV therapeutic dose range (50⿿200 mg/day) in patients with focal seizures including baseline SGTCS.ResultsPatients (efficacy population, N=409) had been diagnosed with epilepsy for a mean±standard deviation duration of 22.2±13.1years. Baseline median SGTCS frequency was 3.0 per 28days. The majority (293, 71.6%) had failed ⿥2 AEDs prior to study enrollment. The median percent reduction from baseline in SGTCS frequency/28days was: placebo, 33.3%; BRV 50mg/day, 66.6% (p<0.001); BRV 100mg/day, 61.2% (p=0.002); and BRV 200mg/day, 82.1% (p<0.001). The ⿥50% responder rate for SGTCS was: placebo, 33.0%; BRV 50mg/day, 61.3% (p=0.003); BRV 100mg/day, 55.0% (p<0.001); and BRV 200mg/day, 64.0% (p<0.001). Freedom from SGTCS was achieved by: placebo, 14.8%; BRV 50mg/day, 22.6%; BRV 100mg/day, 31.0%; and BRV 200mg/day, 36.0% of patients. Time to first SGTCS during the treatment period was longer in patients receiving BRV than placebo (26days vs 8days, hazard ratio 0.55, p<0.001). In the SGTCS safety population (N=487), treatment-emergent adverse events (TEAEs) were reported by 60.6% of patients receiving placebo vs 65.0% of patients receiving BRV ⿥50mg/day. Serious TEAEs were reported by 3.1% placebo vs 3.9% BRV ⿥50mg/day. Discontinuations due to TEAEs were 3.9% placebo vs 6.3% BRV ⿥50mg/day.ConclusionsIn patients with drug-resistant focal seizures, adjunctive BRV is effective in reducing the frequency of SGTCS. Almost one-third (30.4%) of patients were rendered completely free of SGTCS during the 12-week treatment period when taking BRV ⿥50mg/day. BRV was well tolerated, with a TEAE profile consistent with that of the overall study population

Clear-air turbulence trends over the North Atlantic in high-resolution climate models

Clear-air turbulence (CAT) has a large impact on the aviation sector. Our current understanding of how CAT may increase with climate change in future is largely based on simulations from CMIP3 and CMIP5 global climate models (GCMs). However, these models have now been superseded by high-resolution CMIP6 GCMs, which for the first time have grid lengths at which individual turbulence patches may start to be resolved. Here we use a multi-model approach to quantify projected moderate CAT changes over the North Atlantic using CMIP6 models. The influence of the model resolution on CAT projections is analysed. Twenty-one CAT diagnostics are used, in order to represent uncertainties in CAT production mechanisms. Each diagnostic responds differently in time, but the majority display an increase in moderate CAT between 1950 and 2050. Although winter is historically the most turbulent season, there is strong multi-model agreement that autumn and summer will have the greatest overall relative increase in CAT frequency. By 2050, summers are projected to become as turbulent as 1950 winters and autumns. The global-mean seasonal near-surface temperature is used as a comparative metric. For every 1 °C of global near-surface warming, autumn, winter, spring, and summer are projected to have an average of 14%, 9%, 9%, and 14% more moderate CAT, respectively. Our results confirm that the aviation sector should prepare for a more turbulent future

Rachis brittleness in a hybrid–parent barley (Hordeum vulgare) breeding germplasm with different combinations at the non‐brittle rachis genes

Two dominant, closely linked and complementary genes, Btr1 and Btr2, control rachis brittleness in barley. Recessive mutations in any of these genes turn the fragile rachis (brittle) into a tough rachis phenotype (non‐brittle). The cross of parents with alternative mutations in the btr genes leads to a brittle F1 hybrid that presents grain retention problems. We evaluated rachis fragility through a mechanical test and under natural conditions, in F1 crosses with different compositions at the btr genes. Brittleness was significantly higher in Btr1btr1Btr2btr2 crosses compared to hybrids and inbred parents carrying one of the mutations (btr1btr1Btr2Btr2/Btr1Btr1btr2btr2). This fact could jeopardize the efficient harvest of hybrids bearing alternative mutations, reducing the choice of possible crosses for hybrid barley breeding and hindering the exploitation of potential heterotic patterns. Furthermore, non‐brittle hybrids showed higher brittleness than inbreds, suggesting the presence of other dominant factors affecting the trait. In conclusion, this work encourages a deeper study of the genetic control of the rachis brittleness trait and urges the consideration of rachis tenacity as a target for hybrid barley breeding.This work was supported by the Spanish Ministry of Economy, Industry and Competitiveness grants RFP2015 00006‐00‐00, and RTA2012‐00033‐C03‐02, and by the contract “Iberia region hybrid barley variety development and understanding effects of adaptation genes in hybrids,” between CSIC and Syngenta Crop Protection AG, which included funding for MFC PhD scholarship

Northern Hemisphere blocking simulation in current climate models: evaluating progress from the Climate Model Intercomparison Project Phase 5 to 6 and sensitivity to resolution

Global climate models (GCMs) are known to suffer from biases in the simulation of atmospheric blocking, and this study provides an assessment of how blocking is represented by the latest generation of GCMs. It is evaluated (i) how historical CMIP6 (Climate Model Intercomparison Project Phase 6) simulations perform compared to CMIP5 simulations and (ii) how horizontal model resolution affects the simulation of blocking in the CMIP6-HighResMIP (PRIMAVERA – PRocess-based climate sIMulation: AdVances in high-resolution modelling and European climate Risk Assessment) model ensemble, which is designed to address this type of question. Two blocking indices are used to evaluate the simulated mean blocking frequency and blocking persistence for the Euro-Atlantic and Pacific regions in winter and summer against the corresponding estimates from atmospheric reanalysis data. There is robust evidence that CMIP6 models simulate blocking frequency and persistence better than CMIP5 models in the Atlantic and Pacific and during winter and summer. This improvement is sizeable so that, for example, winter blocking frequency in the median CMIP5 model in a large Euro-Atlantic domain is underestimated by 33 % using the absolute geopotential height (AGP) blocking index, whereas the same number is 18 % for the median CMIP6 model. As for the sensitivity of simulated blocking to resolution, it is found that the resolution increase, from typically 100 to 20 km grid spacing, in most of the PRIMAVERA models, which are not re-tuned at the higher resolutions, benefits the mean blocking frequency in the Atlantic in winter and summer and in the Pacific in summer. Simulated blocking persistence, however, is not seen to improve with resolution. Our results are consistent with previous studies suggesting that resolution is one of a number of interacting factors necessary for an adequate simulation of blocking in GCMs. The improvements reported in this study hold promise for further reductions in blocking biases as model development continues

Characterisation of machinable structural polymers in restorative dentistry

Objectives To characterise the mechanical properties of the machinable polymers Pekkton® (Cendres-Meteaux, Biel/Bienne, Switzerland), Lava Ultimate® (3MESPE, Seefeld, Germany), Vita Enamic® (Ivoclar Vivadent, Schaan, Liechtenstein) and the ceramic IPS e.Max Press® (Ivoclar Vivadent, Schaan, Liechtenstein). To determine the structural integrity of full coverage crowns fabricated from these materials. Methods The following tests were conducted: Biaxial flexural strength (BFS) using the piston on 3 balls jig (n = 10); Vickers Hardness (VH) 10 indentations per sample with 10 kg load & 20 s dwell time (n = 5); Hygroscopic Expansion Change (HEC) in artificial saliva over 68 days (n = 5). Structural Strength (SS) of teeth analogues (n = 20) restored with monolithic crowns from the four materials. Mean values and standard deviations for BFS, VH, HEC and SS tests were calculated and compared using one-way ANOVA with post-hoc Tukey’s test at a level of 5% significance. Results BFS: IPS e.Max Press® (317 MPa ± 37 MPa), Pekkton® (227 MPa ± 18 MPa), Lava Ultimate® (145 MPa ± 18 MPa) and Vita Enamic® (137 MPa ± 7 MPa) with a significance between groups of p < 0.0001. VH: IPS e.Max Press® (5064 MPa ± 131 MPa), Vita Enamic® (1976 MPa ± 12 MPa), Lava Ultimate® (924 MPa ± 27 MPa) and Pekkton® (445MPa ± 21 MPa) with a significance between groups of p < 0.0001. HEC (%vol change): Pekkton® (0.14% ± 0.14%), Vita Enamic® (0.38% ± 0.16%) and Lava Ultimate® (1.06% ± 0.17%). SS for full-coverage crowns: Pekkton® (2037 N ± 49 N no fracture), IPS e.Max Press® (1497 N ± 165 N), Lava Ultimate® (1476 N ± 142 N) and Vita Enamic® (1127 N ± 108 N). Significance The properties investigated suggest that full coverage monolithic PEKK crowns possess adequate mechanical and physical properties for use in the posterior region of the mouth. These results must be considered alongside other data including clinical studies

(Re)constructing Dimensions

Compactifying a higher-dimensional theory defined in R^{1,3+n} on an n-dimensional manifold {\cal M} results in a spectrum of four-dimensional (bosonic) fields with masses m^2_i = \lambda_i, where - \lambda_i are the eigenvalues of the Laplacian on the compact manifold. The question we address in this paper is the inverse: given the masses of the Kaluza-Klein fields in four dimensions, what can we say about the size and shape (i.e. the topology and the metric) of the compact manifold? We present some examples of isospectral manifolds (i.e., different manifolds which give rise to the same Kaluza-Klein mass spectrum). Some of these examples are Ricci-flat, complex and K\"{a}hler and so they are isospectral backgrounds for string theory. Utilizing results from finite spectral geometry, we also discuss the accuracy of reconstructing the properties of the compact manifold (e.g., its dimension, volume, and curvature etc) from measuring the masses of only a finite number of Kaluza-Klein modes.Comment: 23 pages, 3 figures, 2 references adde

Description of the resolution hierarchy of the global coupled HadGEM3-GC3.1 model as used in CMIP6 HighResMIP experiments

CMIP6 HighResMIP is a new experimental design for global climate model simulations that aims to assess the impact of model horizontal resolution on climate simulation fidelity. We describe a hierarchy of global coupled model resolutions based on the HadGEM3-GC3.1 model that range from an atmosphere-ocean resolution of 130 km-1° to 25 km-1/12°, all using the same forcings and initial conditions. In order to make such high resolution simulations possible, the experiments have a short 30 year spinup, followed by at least century-long simulations with both constant forcing (to assess drift and the focus of this work), and historic forcing. We assess the change in model biases as a function of both atmosphere and ocean resolution, together with the effectiveness and robustness of this new experimental design. We find reductions in the biases in top of atmosphere radiation components and cloud forcing. There are significant reductions in some common surface climate model biases as resolution is increased, particularly in the Atlantic for sea surface temperature and precipitation, primarily driven by increased ocean resolution. There is also a reduction in drift from the initial conditions both at the surface and in the deeper ocean at higher resolution. Using an eddy-present and eddy-rich ocean resolution enhances the strength of the North Atlantic ocean circulation (boundary currents, overturning circulation and heat transports), while an eddy-present ocean resolution has a considerably reduced Antarctic Circumpolar Current strength. All models have a reasonable representation of El Nino – Southern Oscillation. In general the biases present after 30 years of simulations do not change character markedly over longer timescales, justifying the experimental design

Options to Reform the European Union Legislation on GMOs: Scope and Definitions

We discuss options to reform the EU genetically modified organisms (GMO) regulatory framework, make risk assessment and decision-making more consistent with scientific principles, and lay the groundwork for international coherence. The first in a three-part series, this article focuses on reform options related to the scope of the legislation and the GMO definition