Efficient training sets for surrogate models of tokamak turbulence with Active Deep Ensembles

Model-based plasma scenario development lies at the heart of the design and operation of future fusion powerplants. Including turbulent transport in integrated models is essential for delivering a successful roadmap towards operation of ITER and the design of DEMO-class devices. Given the highly iterative nature of integrated models, fast machine-learning-based surrogates of turbulent transport are fundamental to fulfil the pressing need for faster simulations opening up pulse design, optimization, and flight simulator applications. A significant bottleneck is the generation of suitably large training datasets covering a large volume in parameter space, which can be prohibitively expensive to obtain for higher fidelity codes. In this work, we propose ADEPT (Active Deep Ensembles for Plasma Turbulence), a physics-informed, two-stage Active Learning strategy to ease this challenge. Active Learning queries a given model by means of an acquisition function that identifies regions where additional data would improve the surrogate model. We provide a benchmark study using available data from the literature for the QuaLiKiz quasilinear transport model. We demonstrate quantitatively that the physics-informed nature of the proposed workflow reduces the need to perform simulations in stable regions of the parameter space, resulting in significantly improved data efficiency. We show an up to a factor of 20 reduction in training dataset size needed to achieve the same performance as random sampling. We then validate the surrogates on multichannel integrated modelling of ITG-dominated JET scenarios and demonstrate that they recover the performance of QuaLiKiz to better than 10\%. This matches the performance obtained in previous work, but with two orders of magnitude fewer training data points.Comment: Submitted to Nuclear Fusion. Comments welcom

Yukawa Unified Supersymmetric SO(10) Model: Cosmology, Rare Decays and Collider Searches

It has recently been pointed out that viable sparticle mass spectra can be generated in Yukawa unified SO(10) supersymmetric grand unified models consistent with radiative breaking of electroweak symmetry. Model solutions are obtained only if $\tan\beta \sim 50$, $\mu <0$ and positive $D$-term contributions to scalar masses from SO(10) gauge symmetry breaking are used. In this paper, we attempt to systematize the parameter space regions where solutions are obtained. We go on to calculate the relic density of neutralinos as a function of parameter space. No regions of the parameter space explored were actually cosmologically excluded, and very reasonable relic densities were found in much of parameter space. Direct neutralino detection rates could exceed 1 event/kg/day for a $^{73}$Ge detector, for low values of GUT scale gaugino mass $m_{1/2}$. We also calculate the branching fraction for $b\to s \gamma$ decays, and find that it is beyond the 95% CL experimental limits in much, but not all, of the parameter space regions explored. However, recent claims have been made that NLO effects can reverse the signs of certain amplitudes in the $b\to s\gamma$ calculation, leading to agreement between theory and experiment in Yukawa unified SUSY models. For the Fermilab Tevatron collider, significant regions of parameter space can be explored via $b\bar{b}A$ and $b\bar{b}H$ searches. There also exist some limited regions of parameter space where a trilepton signal can be seen at TeV33. Finally, there exist significant regions of parameter space where direct detection of bottom squark pair production can be made, especially for large negative values of the GUT parameter $A_0$.Comment: Added comparison to Blazek/Raby results and added Comments on de Boer et al. b->s gamma result

Meta-analysis across Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium provides evidence for an association of serum vitamin D with pulmonary function

The role that vitamin D plays in pulmonary function remains uncertain. Epidemiological studies reported mixed findings for serum 25-hydroxyvitamin D (25(OH)D)-pulmonary function association. We conducted the largest cross-sectional meta-analysis of the 25(OH)D-pulmonary function association to date, based on nine European ancestry (EA) cohorts (n 22 838) and five African ancestry (AA) cohorts (n 4290) in the Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium. Data were analysed using linear models by cohort and ancestry. Effect modification by smoking status (current/former/never) was tested. Results were combined using fixed-effects meta-analysis. Mean serum 25(OH)D was 68 (SD 29) nmol/l for EA and 49 (SD 21) nmol/l for AA. For each 1 nmol/l higher 25(OH)D, forced expiratory volume in the 1st second (FEV1) was higher by 1.1 ml in EA (95 % CI 0.9, 1.3; P< 0.0001) and 1.8 ml (95 % CI 1.1, 2.5; P< 0.0001) in AA (P-race (difference) = 0.06), and forced vital capacity (FVC) was higher by 1.3 ml in EA (95 % CI 1.0, 1.6; P <0.0001) and 1.5 ml (95 % CI 0.8, 2.3; P= 0.0001) in AA (P-race difference = 0.56). Among EA, the 25(OH)D-FVC association was stronger in smokers: per 1 nmol/l higher 25(OH) D, FVC was higher by 1.7 ml (95 % CI 1.1, 2.3) for current smokers and 1.7 ml (95 % CI 1.2, 2.1) for former smokers, compared with 0.8 ml (95 % CI 0.4, 1.2) for never smokers. In summary, the 25(OH)D associations with FEV1 and FVC were positive in both ancestries. In EA, a stronger association was observed for smokers compared with never smokers, which supports the importance of vitamin D in vulnerable populations

Traditional Excluding Forces: A Review of the Quantitative Literature on the Economic Situation of Indigenous Peoples, Afro-Descendants, and People Living with Disability

Unequal income distribution in Latin America and the Caribbean is linked to unequal distributions of (human and physical) assets and differential access to markets and services. These circumstances, and the accompanying social tensions, need to be understood in terms of traditional fragmenting forces; the sectors of the population who experience unfavorable outcomes are also recognized by characteristics such as ethnicity, race, gender and physical disability. In addition to reviewing the general literature on social exclusion, this paper surveys several more specific topics: i) relative deprivation (in land and housing, physical infrastructure, health and income); ii) labor market issues, including access to labor markets in general, as well as informality, segregation and discrimination; iii) the transaction points of political representation, social protection and violence; and iv) areas where analysis remains weak and avenues for further research in the region

The structural plasticity of white matter networks following anterior temporal lobe resection

Anterior temporal lobe resection is an effective treatment for refractory temporal lobe epilepsy. The structural consequences of such surgery in the white matter, and how these relate to language function after surgery remain unknown. We carried out a longitudinal study with diffusion tensor imaging in 26 left and 20 right temporal lobe epilepsy patients before and a mean of 4.5 months after anterior temporal lobe resection. The whole-brain analysis technique tract-based spatial statistics was used to compare pre- and postoperative data in the left and right temporal lobe epilepsy groups separately. We observed widespread, significant, mean 7%, decreases in fractional anisotropy in white matter networks connected to the area of resection, following both left and right temporal lobe resections. However, we also observed a widespread, mean 8%, increase in fractional anisotropy after left anterior temporal lobe resection in the ipsilateral external capsule and posterior limb of the internal capsule, and corona radiata. These findings were confirmed on analysis of the native clusters and hand drawn regions of interest. Postoperative tractography seeded from this area suggests that this cluster is part of the ventro-medial language network. The mean pre- and postoperative fractional anisotropy and parallel diffusivity in this cluster were significantly correlated with postoperative verbal fluency and naming test scores. In addition, the percentage change in parallel diffusivity in this cluster was correlated with the percentage change in verbal fluency after anterior temporal lobe resection, such that the bigger the increase in parallel diffusivity, the smaller the fall in language proficiency after surgery. We suggest that the findings of increased fractional anisotropy in this ventro-medial language network represent structural reorganization in response to the anterior temporal lobe resection, which may damage the more susceptible dorso-lateral language pathway. These findings have important implications for our understanding of brain injury and rehabilitation, and may also prove useful in the prediction and minimization of postoperative language deficits

Genome-wide association meta-analysis in 269,867 individuals identifies new genetic and functional links to intelligence

Intelligence is highly heritable(1) and a major determinant of human health and well-being(2). Recent genome-wide meta-analyses have identified 24 genomic loci linked to variation in intelligence3-7, but much about its genetic underpinnings remains to be discovered. Here, we present a large-scale genetic association study of intelligence (n = 269,867), identifying 205 associated genomic loci (190 new) and 1,016 genes (939 new) via positional mapping, expression quantitative trait locus (eQTL) mapping, chromatin interaction mapping, and gene-based association analysis. We find enrichment of genetic effects in conserved and coding regions and associations with 146 nonsynonymous exonic variants. Associated genes are strongly expressed in the brain, specifically in striatal medium spiny neurons and hippocampal pyramidal neurons. Gene set analyses implicate pathways related to nervous system development and synaptic structure. We confirm previous strong genetic correlations with multiple health-related outcomes, and Mendelian randomization analysis results suggest protective effects of intelligence for Alzheimer's disease and ADHD and bidirectional causation with pleiotropic effects for schizophrenia. These results are a major step forward in understanding the neurobiology of cognitive function as well as genetically related neurological and psychiatric disorders.Peer reviewe

Analysis of protein-coding genetic variation in 60,706 humans

Large-scale reference data sets of human genetic variation are critical for the medical and functional interpretation of DNA sequence changes. We describe the aggregation and analysis of high-quality exome (protein-coding region) sequence data for 60,706 individuals of diverse ethnicities generated as part of the Exome Aggregation Consortium (ExAC). This catalogue of human genetic diversity contains an average of one variant every eight bases of the exome, and provides direct evidence for the presence of widespread mutational recurrence. We have used this catalogue to calculate objective metrics of pathogenicity for sequence variants, and to identify genes subject to strong selection against various classes of mutation; identifying 3,230 genes with near-complete depletion of truncating variants with 72% having no currently established human disease phenotype. Finally, we demonstrate that these data can be used for the efficient filtering of candidate disease-causing variants, and for the discovery of human “knockout” variants in protein-coding genes

Genetic diversity fuels gene discovery for tobacco and alcohol use

Tobacco and alcohol use are heritable behaviours associated with 15% and 5.3% of worldwide deaths, respectively, due largely to broad increased risk for disease and injury(1-4). These substances are used across the globe, yet genome-wide association studies have focused largely on individuals of European ancestries(5). Here we leveraged global genetic diversity across 3.4 million individuals from four major clines of global ancestry (approximately 21% non-European) to power the discovery and fine-mapping of genomic loci associated with tobacco and alcohol use, to inform function of these loci via ancestry-aware transcriptome-wide association studies, and to evaluate the genetic architecture and predictive power of polygenic risk within and across populations. We found that increases in sample size and genetic diversity improved locus identification and fine-mapping resolution, and that a large majority of the 3,823 associated variants (from 2,143 loci) showed consistent effect sizes across ancestry dimensions. However, polygenic risk scores developed in one ancestry performed poorly in others, highlighting the continued need to increase sample sizes of diverse ancestries to realize any potential benefit of polygenic prediction.Peer reviewe