The Kolmogorov-Smirnov test for the CMB

We investigate the statistics of the cosmic microwave background using the Kolmogorov-Smirnov test. We show that, when we correctly de-correlate the data, the partition function of the Kolmogorov stochasticity parameter is compatible with the Kolmogorov distribution and, contrary to previous claims, the CMB data are compatible with Gaussian fluctuations with the correlation function given by standard Lambda-CDM. We then use the Kolmogorov-Smirnov test to derive upper bounds on residual point source power in the CMB, and indicate the promise of this statistics for further datasets, especially Planck, to search for deviations from Gaussianity and for detecting point sources and Galactic foregrounds.Comment: Improved significance of the results (which remain unchanged) by using patches instead of ring segments in the analysis. Added sky maps of the Kolmogorov-parameter for original and de-correlated CMB ma

Photon mixing in universes with large extra-dimensions

In presence of a magnetic field, photons can mix with any particle having a two-photon vertex. In theories with large compact extra-dimensions, there exists a hierachy of massive Kaluza-Klein gravitons that couple to any photon entering a magnetic field. We study this mixing and show that, in comparison with the four dimensional situation where the photon couples only to the massless graviton, the oscillation effect may be enhanced due to the existence of a large number of Kaluza-Klein modes. We give the conditions for such an enhancement and then investigate the cosmological and astrophysical consequences of this phenomenon; we also discuss some laboratory experiments. Axions also couple to photons in the same way; we discuss the effect of the existence of bulk axions in universes with large extra-dimensions. The results can also be applied to neutrino physics with extra-dimensions.Comment: 41 pages, LaTex, 6 figure

The genetic architecture of the human cerebral cortex

INTRODUCTION The cerebral cortex underlies our complex cognitive capabilities. Variations in human cortical surface area and thickness are associated with neurological, psychological, and behavioral traits and can be measured in vivo by magnetic resonance imaging (MRI). Studies in model organisms have identified genes that influence cortical structure, but little is known about common genetic variants that affect human cortical structure. RATIONALE To identify genetic variants associated with human cortical structure at both global and regional levels, we conducted a genome-wide association meta-analysis of brain MRI data from 51,665 individuals across 60 cohorts. We analyzed the surface area and average thickness of the whole cortex and 34 cortical regions with known functional specializations. RESULTS We identified 306 nominally genome-wide significant loci (P < 5 × 10−8) associated with cortical structure in a discovery sample of 33,992 participants of European ancestry. Of the 299 loci for which replication data were available, 241 loci influencing surface area and 14 influencing thickness remained significant after replication, with 199 loci passing multiple testing correction (P < 8.3 × 10−10; 187 influencing surface area and 12 influencing thickness). Common genetic variants explained 34% (SE = 3%) of the variation in total surface area and 26% (SE = 2%) in average thickness; surface area and thickness showed a negative genetic correlation (rG = −0.32, SE = 0.05, P = 6.5 × 10−12), which suggests that genetic influences have opposing effects on surface area and thickness. Bioinformatic analyses showed that total surface area is influenced by genetic variants that alter gene regulatory activity in neural progenitor cells during fetal development. By contrast, average thickness is influenced by active regulatory elements in adult brain samples, which may reflect processes that occur after mid-fetal development, such as myelination, branching, or pruning. When considered together, these results support the radial unit hypothesis that different developmental mechanisms promote surface area expansion and increases in thickness. To identify specific genetic influences on individual cortical regions, we controlled for global measures (total surface area or average thickness) in the regional analyses. After multiple testing correction, we identified 175 loci that influence regional surface area and 10 that influence regional thickness. Loci that affect regional surface area cluster near genes involved in the Wnt signaling pathway, which is known to influence areal identity. We observed significant positive genetic correlations and evidence of bidirectional causation of total surface area with both general cognitive functioning and educational attainment. We found additional positive genetic correlations between total surface area and Parkinson’s disease but did not find evidence of causation. Negative genetic correlations were evident between total surface area and insomnia, attention deficit hyperactivity disorder, depressive symptoms, major depressive disorder, and neuroticism. CONCLUSION This large-scale collaborative work enhances our understanding of the genetic architecture of the human cerebral cortex and its regional patterning. The highly polygenic architecture of the cortex suggests that distinct genes are involved in the development of specific cortical areas. Moreover, we find evidence that brain structure is a key phenotype along the causal pathway that leads from genetic variation to differences in general cognitive function

Geographical and temporal distribution of SARS-CoV-2 clades in the WHO European Region, January to June 2020

We show the distribution of SARS-CoV-2 genetic clades over time and between countries and outline potential genomic surveillance objectives. We applied three available genomic nomenclature systems for SARS-CoV-2 to all sequence data from the WHO European Region available during the COVID-19 pandemic until 10 July 2020. We highlight the importance of real-time sequencing and data dissemination in a pandemic situation. We provide a comparison of the nomenclatures and lay a foundation for future European genomic surveillance of SARS-CoV-2.Peer reviewe

New insights into the genetic etiology of Alzheimer's disease and related dementias

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele

085 Systolic vs diastolic acquisition in cardiovascular magnetic resonance myocardial perfusion imaging

Introduction: Although differences in systolic and diastolic myocardial blood flow (MBF) estimates have been shown in healthy volunteers, the impact of cardiac phase on detecting coronary artery disease (CAD) using cardiovascular magnetic resonance (CMR) myocardial perfusion imaging is unknown. The aim of this study was to compare MBF estimates in systole and diastole in patients with suspected CAD and determine if either phase has greater diagnostic accuracy.&lt;p&gt;&lt;/p&gt; Methods: Following invasive coronary angiography, 40 patients (68% men, 64±8 yrs) underwent stress/rest perfusion-CMR (1.5T Philips) which was acquired at mid-systole and end-diastole simultaneously. Based on angiographic stenosis &#62;70% (quantitative coronary angiography), patients were grouped as having “CAD” or “no CAD.” In patients with CAD, myocardial segments were classified as “stenosis-dependent” (downstream of a significant stenosis) or “remote.” For each segment, MBF (Fermi-constrained deconvolution) and myocardial perfusion reserve (MPR) were calculated. The diagnostic accuracy of each phase was determined with receiver operator characteristic analysis.&lt;p&gt;&lt;/p&gt; Results: 21 patients (53%) had CAD. A typical example of a patient with ischaemia is shown in Abstract 085 figure 1. Resting MBF was similar in the two cardiac phases for both normal and CAD patients (all p values &#62;0.05). MBF at stress was greater in diastole than systole in normal, remote and stenosis-dependent segments (3.75±1.5 vs 3.15±1.1 ml/g/min; 2.75±1.20 vs 2.38±0.99 ml/g/min; 2.49±1.07 vs 2.23±0.90 ml/g/min; all p values &#60;0.01). MPR was also greater in diastole than systole in all three segment groups (all p values &#60;0.05) (Abstract 085 figure 2). On receiver operator characteristic analysis, the optimal MPR cut-off for the detection of CAD was 1.95 for systole and 2.04 for diastole (area under curve 0.82 vs 0.79; p=0.30)

Systolic versus diastolic acquisition in myocardial perfusion MR imaging

&lt;br&gt;Purpose: To compare myocardial blood flow (MBF) at systole and diastole and determine the diagnostic accuracy of both phases in patients suspected of having coronary artery disease (CAD).&lt;/br&gt; &lt;br&gt;Materials and Methods: The study was approved by the regional ethics committee, and all patients gave written informed consent. After coronary angiography, 40 patients (27 men; mean age, 64 years ± 8) underwent stress-rest perfusion magnetic resonance (MR) imaging at 1.5 T, with images aquired simultaneously at end systole and middiastole. Patients were classified as having CAD (stenosis &#62;70%) or no significant CAD. In patients with CAD, myocardial segments were classified as stenosis-dependent (downstream of significant stenosis) or remote. MBF and myocardial perfusion reserve (MPR) were calculated for each segment, and mean values in each phase were compared with paired t tests. The diagnostic accuracy of each phase was determined with receiver operating characteristic (ROC) analysis. &lt;/br&gt; &lt;br&gt;Results: Twenty-one of the 40 patients (53%) had CAD. Resting MBF was similar in both phases for patients with and patients without CAD (P &#62; .05). Stress MBF was greater in diastole than systole in normal, remote, and stenosis-dependent segments (3.75 mL/g/min ± 1.50 vs 3.15 mL/g/min ± 1.10, respectively, for normal segments; 2.75 mL/g/min ± 1.20 vs 2.38 mL/g/min ± 0.99, respectively, for remote segments; 2.49 mL/g/min ± 1.07 vs 2.23 mL/g/min ± 0.90, respectively, for stenosis-dependent segments; P &#60;.01). MPR was greater in diastole than systole in all segment groups (P &#60; .05). The diagnostic accuracies at diastole and systole were similar (area under the ROC curve = 0.79 and 0.82, respectively; P = .30). &lt;/br&gt; &lt;br&gt;Conclusion: Myocardial perfusion MR estimates of stress MBF and MPR were greater in diastole than systole in patients with and patients without CAD. However, both phases had similar diagnostic accuracy. These observations may be relevant to other dynamic perfusion methods, including computed tomography and echocardiography. &lt;/br&gt