Intramode and Fermi relaxation in CO2, their influence on multiple-pass, short-pulse energy extraction

Analytical, experimental and numerical results concerning the influence of intramode and Fermi relaxation on multiple-pass, nanosecond-pulse energy extraction are presented. Multiple-pass energy extraction experiments show satisfactory agreement with the analytical and numerical calculations which predict a significant increase in extracted energy. In three passes, an amount of 9.7 J/l was extracted at an efficiency of 4.3%, These values are taken with respect to the volume of the beam inside the amplifier. In a single pass only 3.5 J/l was extracted

Impact of dynamic computed tomographic angiography on endograft sizing for endovascular aneurysm repair.

Contains fulltext : 80349.pdf (publisher's version ) (Open Access)PURPOSE: To quantify dynamic changes in aortoiliac dimensions using dynamic electrocardiographically (ECG)-gated computed tomographic angiography (CTA) and to investigate any potential impact on preoperative endograft sizing in relation to observer variability. METHODS: Dynamic ECG-gated CTA was performed in 18 patients with abdominal aortic aneurysms. Postprocessing resulted in 11 datasets per patient: 1 static CTA and 10 dynamic CTA series. Vessel diameter, length, and angulation were measured for all phases of the cardiac cycle. The differences between diastolic and systolic aneurysm dimensions were analyzed for significance using paired t tests. To assess intraobserver variability, 20 randomly selected datasets were analyzed twice. Intraobserver repeatability coefficients (RC) were calculated using Bland-Altman analysis. RESULTS: Mean aortic diameter at the proximal neck was 21.4+/-3.0 mm at diastole and 23.2+/-2.9 mm at systole, a mean increase of 1.8+/-0.4 mm (8.5%, p<0.01). The RC for the aortic diameter at the level of the proximal aneurysm neck was 1.9 mm (8.9%). At the distal sealing zones, the mean increase in diameter was 1.7+/-0.3 mm (14.1%, p<0.01) for the right and 1.8+/-0.5 mm (14.2%, p<0.01) for the left common iliac artery (CIA). At both distal sealing zones, the mean increase in CIA diameter exceeded the RC (10.0% for the right CIA and 12.6% for the left CIA). CONCLUSION: The observed changes in aneurysm dimension during the cardiac cycle are small and in the range of intraobserver variability, so dynamic changes in proximal aneurysm neck diameter and aneurysm length likely have little impact on preoperative endograft selection. However, changes in diameter at the distal sealing zones may be relevant to sizing, so distal oversizing of up to 20% should be considered to prevent distal type I endoleak

Flavonoids Influence Monocytic GTPase Activity and Are Protective in Experimental Allergic Encephalitis

In the chronic disabling disease multiple sclerosis (MS), migration of monocytes across the blood-brain barrier is a crucial step in the formation of new lesions in the central nervous system (CNS). Infiltrating monocyte-derived macrophages secrete inflammatory mediators such as oxygen radicals, which contribute to axonal demyelination and damage, resulting in neurological deficits. Flavonoids are compounds occurring naturally in food, which scavenge oxygen radicals and have antiinflammatory properties. To investigate whether they might suppress clinical symptoms in MS, we treated rats sensitized for acute and chronic experimental allergic encephalomyelitis, an experimental model of MS, with flavonoids. We demonstrated that the flavonoid luteolin substantially suppressed clinical symptoms and prevented relapse when administered either before or after disease onset. Luteolin treatment resulted in reduced inflammation and axonal damage in the CNS by preventing monocyte migration across the brain endothelium. Luteolin influenced migration by modulating the activity of Rho GTPases, signal transducers involved in transendothelial migration. Oral administration of luteolin also significantly reduced clinical symptoms

Is optimising gout treatment the key to closing the mortality gap in gout patients?

Pathophysiology and treatment of rheumatic disease

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

Functional mechanisms underlying pleiotropic risk alleles at the 19p13.1 breast-ovarian cancer susceptibility locus

A locus at 19p13 is associated with breast cancer (BC) and ovarian cancer (OC) risk. Here we analyse 438 SNPs in this region in 46,451 BC and 15,438 OC cases, 15,252 BRCA1 mutation carriers and 73,444 controls and identify 13 candidate causal SNPs associated with serous OC (P=9.2 × 10-20), ER-negative BC (P=1.1 × 10-13), BRCA1-associated BC (P=7.7 × 10-16) and triple negative BC (P-diff=2 × 10-5). Genotype-gene expression associations are identified for candidate target genes ANKLE1 (P=2 × 10-3) and ABHD8 (P<2 × 10-3). Chromosome conformation capture identifies interactions between four candidate SNPs and ABHD8, and luciferase assays indicate six risk alleles increased transactivation of the ADHD8 promoter. Targeted deletion of a region containing risk SNP rs56069439 in a putative enhancer induces ANKLE1 downregulation; and mRNA stability assays indicate functional effects for an ANKLE1 3′-UTR SNP. Altogether, these data suggest that multiple SNPs at 19p13 regulate ABHD8 and perhaps ANKLE1 expression, and indicate common mechanisms underlying breast and ovarian cancer risk