Variational Multiscale Stabilization and the Exponential Decay of Fine-scale Correctors

This paper addresses the variational multiscale stabilization of standard finite element methods for linear partial differential equations that exhibit multiscale features. The stabilization is of Petrov-Galerkin type with a standard finite element trial space and a problem-dependent test space based on pre-computed fine-scale correctors. The exponential decay of these correctors and their localisation to local cell problems is rigorously justified. The stabilization eliminates scale-dependent pre-asymptotic effects as they appear for standard finite element discretizations of highly oscillatory problems, e.g., the poor $L^2$ approximation in homogenization problems or the pollution effect in high-frequency acoustic scattering

2019 international consensus on cardiopulmonary resuscitation and emergency cardiovascular care science with treatment recommendations : summary from the basic life support; advanced life support; pediatric life support; neonatal life support; education, implementation, and teams; and first aid task forces

The International Liaison Committee on Resuscitation has initiated a continuous review of new, peer-reviewed, published cardiopulmonary resuscitation science. This is the third annual summary of the International Liaison Committee on Resuscitation International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations. It addresses the most recent published resuscitation evidence reviewed by International Liaison Committee on Resuscitation Task Force science experts. This summary addresses the role of cardiac arrest centers and dispatcher-assisted cardiopulmonary resuscitation, the role of extracorporeal cardiopulmonary resuscitation in adults and children, vasopressors in adults, advanced airway interventions in adults and children, targeted temperature management in children after cardiac arrest, initial oxygen concentration during resuscitation of newborns, and interventions for presyncope by first aid providers. Members from 6 International Liaison Committee on Resuscitation task forces have assessed, discussed, and debated the certainty of the evidence on the basis of the Grading of Recommendations, Assessment, Development, and Evaluation criteria, and their statements include consensus treatment recommendations. Insights into the deliberations of the task forces are provided in the Justification and Evidence to Decision Framework Highlights sections. The task forces also listed priority knowledge gaps for further research

Association study in the 5q31-32 linkage region for schizophrenia using pooled DNA genotyping

<p>Abstract</p> <p>Background</p> <p>Several linkage studies suggest that chromosome 5q31-32 might contain risk loci for schizophrenia (SZ). We wanted to identify susceptibility genes for schizophrenia within this region.</p> <p>Methods</p> <p>We saturated the interval between markers D5S666 and D5S436 with 90 polymorphic microsatellite markers and genotyped two sets of DNA pools consisting of 300 SZ patients of Bulgarian origin and their 600 parents. Positive associations were followed-up with SNP genotyping.</p> <p>Results</p> <p>Nominally significant evidence for association (p < 0.05) was found for seven markers (D5S0023i, IL9, RH60252, 5Q3133_33, D5S2017, D5S1481, D5S0711i) which were then individually genotyped in the trios. The predicted associations were confirmed for two of the markers: D5S2017, localised in the <it>SPRY4-FGF1 </it>locus (p = 0.004) and IL9, localized within the IL9 gene (p = 0.014). Fine mapping was performed using single nucleotide polymorphisms (SNPs) around D5S2017 and IL9. In each region four SNPs were chosen and individually genotyped in our full sample of 615 SZ trios. Two SNPs showed significant evidence for association: rs7715300 (p = 0.001) and rs6897690 (p = 0.032). Rs7715300 is localised between the <it>TGFBI </it>and <it>SMAD5 </it>genes and rs6897690 is within the <it>SPRY4 </it>gene.</p> <p>Conclusion</p> <p>Our screening of 5q31-32 implicates three potential candidate genes for SZ: <it>SMAD5</it>, <it>TGFBI </it>and <it>SPRY4</it>.</p

On the Wegener granulomatosis associated region on chromosome 6p21.3

BACKGROUND: Wegener granulomatosis (WG) belongs to the heterogeneous group of systemic vasculitides. The multifactorial pathophysiology of WG is supposedly caused by yet unknown environmental influence(s) on the basis of genetic predisposition. The presence of anti-neutrophil cytoplasmic antibodies (ANCA) in the plasma of patients and genetic involvement of the human leukocyte antigen system reflect an autoimmune background of the disease. Strong associations were revealed with WG by markers located in the major histocompatibility complex class II (MHC II) region in the vicinity of human leukocyte antigen (HLA)-DPB1 and the retinoid X receptor B (RXRB) loci. In order to define the involvement of the 6p21.3 region in WG in more detail this previous population-based association study was expanded here to the respective 3.6 megabase encompassing this region on chromosome 6. The RXRB gene was analysed as well as a splice-site variation of the butyrophilin-like (BTNL2) gene which is also located within the respective region. The latter polymorphism has been evaluated here as it appears as a HLA independent susceptibility factor in another granulomatous disorder, sarcoidosis. METHODS: 150–180 German WG patients and a corresponding cohort of healthy controls (n = 100–261) were used in a two-step study. A panel of 94 microsatellites was designed for the initial step using a DNA pooling approach. Markers with significantly differing allele frequencies between patient and control pools were individually genotyped. The RXRB gene was analysed for single strand conformation polymorphisms (SSCP) and restriction fragment length polymorphisms (RFLP). The splice-site polymorphism in the BTNL2 gene was also investigated by RFLP analysis. RESULTS: A previously investigated microsatellite (#1.0.3.7, Santa Cruz genome browser (UCSC) May 2004 Freeze localisation: chr6:31257596-34999883), which was used as a positive control, remained associated throughout the whole two-step approach. Yet, no additional evidence for association of other microsatellite markers was found in the entire investigated region. Analysis of the RXRB gene located in the WG associated region revealed associations of two variations (rs10548957 p(allelic )= 0.02 and rs6531 p(allelic )= 5.20 × 10(-5), OR = 1.88). Several alleles of markers located between HLA-DPB1, SNP rs6531 and microsatellite 1.0.3.7 showed linkage disequilibrium with r(2 )values exceeding 0.10. Significant differences were not demonstrable for the sarcoidosis associated splice-site variation (rs2076530 p(allelic )= 0.80) in our WG cohort. CONCLUSION: Since a microsatellite flanking the RXRB gene and two intragenic polymorphisms are associated significantly with WG on chromosome 6p21.3, further investigations should be focussed on extensive fine-mapping in this region by densely mapping with additional markers such as SNPs. This strategy may reveal even deeper insights into the genetic contributions of the respective region for the pathogenesis of WG

Statistical indicators useful in real spectrum location

In this paper some new results are described, useful for locating the spectrum of a matrix A through mean, standard deviation and third centered moment of the spectrum distribution which can be expressed in terms of traces

Sequence of a complete chicken BG haplotype shows dynamic expansion and contraction of two gene lineages with particular expression patterns.

Many genes important in immunity are found as multigene families. The butyrophilin genes are members of the B7 family, playing diverse roles in co-regulation and perhaps in antigen presentation. In humans, a fixed number of butyrophilin genes are found in and around the major histocompatibility complex (MHC), and show striking association with particular autoimmune diseases. In chickens, BG genes encode homologues with somewhat different domain organisation. Only a few BG genes have been characterised, one involved in actin-myosin interaction in the intestinal brush border, and another implicated in resistance to viral diseases. We characterise all BG genes in B12 chickens, finding a multigene family organised as tandem repeats in the BG region outside the MHC, a single gene in the MHC (the BF-BL region), and another single gene on a different chromosome. There is a precise cell and tissue expression for each gene, but overall there are two kinds, those expressed by haemopoietic cells and those expressed in tissues (presumably non-haemopoietic cells), correlating with two different kinds of promoters and 5' untranslated regions (5'UTR). However, the multigene family in the BG region contains many hybrid genes, suggesting recombination and/or deletion as major evolutionary forces. We identify BG genes in the chicken whole genome shotgun sequence, as well as by comparison to other haplotypes by fibre fluorescence in situ hybridisation, confirming dynamic expansion and contraction within the BG region. Thus, the BG genes in chickens are undergoing much more rapid evolution compared to their homologues in mammals, for reasons yet to be understood.This is the final published version. It was originally published by PLOS in PLOS Genetics here: http://www.plosgenetics.org/article/info%3Adoi%2F10.1371%2Fjournal.pgen.1004417

2019 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations

The International Liaison Committee on Resuscitation has initiated a continuous review of new, peer-reviewed, published cardiopulmonary resuscitation science. This is the third annual summary of the International Liaison Committee on Resuscitation International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations. It addresses the most recent published resuscitation evidence reviewed by International Liaison Committee on Resuscitation Task Force science experts. This summary addresses the role of cardiac arrest centers and dispatcher-assisted cardiopulmonary resuscitation, the role of extracorporeal cardiopulmonary resuscitation in adults and children, vasopressors in adults, advanced airway interventions in adults and children, targeted temperature management in children after cardiac arrest, initial oxygen concentration during resuscitation of newborns, and interventions for presyncope by first aid providers. Members from 6 International Liaison Committee on Resuscitation task forces have assessed, discussed, and debated the certainty of the evidence on the basis of the Grading of Recommendations, Assessment, Development, and Evaluation criteria, and their statements include consensus treatment recommendations. Insights into the deliberations of the task forces are provided in the Justification and Evidence to Decision Framework Highlights sections. The task forces also listed priority knowledge gaps for further research