Cyclic changes of blood echogenicity in high-frequency ultrasound

Ultrasound images from human arteries obtained in vivo with an intravascular 30 MHz ultrasound imaging device show that blood echogenicity changes during the cardiac cycle. Quantitative measurements of blood echogenicity during the cardiac cycle suggest that these variations may be related to changes in the state of erythrocyte aggregation, which are induced by varying shear rate

Mechanical features and in vivo imaging of a polymer stent

A polyethylene-terephthalate (PETP, polyester), self-expanding, braided mesh stent has been developed for percutaneous (coronary) arterial implantation. In vitro measurements showed that the radial pressure delivered by this device was similar to a self-expanding, stainless steel stent. Due to hysteresis-like behaviour, it proved necessary to mount the polymer stent on the delivery system immediately before the placement procedure, and to select a diameter in the unconstrained condition, which was 60% larger than the diameter of the target vessel. Eight polyester stents were implanted in peripheral arteries of four pigs. Except for heparin during the implantation procedure, antithrombotic or antiplatelet drugs were not administered. After four weeks repeat angiography revealed that one of the stents was subtotally occluded. At autopsy, two other stents proved to be located in the aortic bifurcation, probably due to failure of the delivery system. Quantitative angiographic assessment showed that the mean luminal diameters at the site of stent placement were 3.3±0.2 mm before, 3.2±0.2 mm immediately after, and 2.7±0.5 mm at four weeks after implantation. Intravascular ultrasound (IVUS) examination after 4 weeks could identify the individual struts of the stents, as well as their length. In addition, a description of the extent of neointimal hyperplasia was feasible. The IVUS assessment was validated by histological examination. In conclusion, polyester stents can be constructed with mechanical properties similar to stainless steel stents. After implantation in porcine peripheral arteries, five of six correctly placed stents were patent at four weeks. Imaging of stents by angiography and IVUS provided complementary information

Identification of independent association signals and putative functional variants for breast cancer risk through fine-scale mapping of the 12p11 locus.

BACKGROUND: Multiple recent genome-wide association studies (GWAS) have identified a single nucleotide polymorphism (SNP), rs10771399, at 12p11 that is associated with breast cancer risk. METHOD: We performed a fine-scale mapping study of a 700 kb region including 441 genotyped and more than 1300 imputed genetic variants in 48,155 cases and 43,612 controls of European descent, 6269 cases and 6624 controls of East Asian descent and 1116 cases and 932 controls of African descent in the Breast Cancer Association Consortium (BCAC; http://bcac.ccge.medschl.cam.ac.uk/ ), and in 15,252 BRCA1 mutation carriers in the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). Stepwise regression analyses were performed to identify independent association signals. Data from the Encyclopedia of DNA Elements project (ENCODE) and the Cancer Genome Atlas (TCGA) were used for functional annotation. RESULTS: Analysis of data from European descendants found evidence for four independent association signals at 12p11, represented by rs7297051 (odds ratio (OR) = 1.09, 95 % confidence interval (CI) = 1.06-1.12; P = 3 × 10(-9)), rs805510 (OR = 1.08, 95 % CI = 1.04-1.12, P = 2 × 10(-5)), and rs1871152 (OR = 1.04, 95 % CI = 1.02-1.06; P = 2 × 10(-4)) identified in the general populations, and rs113824616 (P = 7 × 10(-5)) identified in the meta-analysis of BCAC ER-negative cases and BRCA1 mutation carriers. SNPs rs7297051, rs805510 and rs113824616 were also associated with breast cancer risk at P < 0.05 in East Asians, but none of the associations were statistically significant in African descendants. Multiple candidate functional variants are located in putative enhancer sequences. Chromatin interaction data suggested that PTHLH was the likely target gene of these enhancers. Of the six variants with the strongest evidence of potential functionality, rs11049453 was statistically significantly associated with the expression of PTHLH and its nearby gene CCDC91 at P < 0.05. CONCLUSION: This study identified four independent association signals at 12p11 and revealed potentially functional variants, providing additional insights into the underlying biological mechanism(s) for the association observed between variants at 12p11 and breast cancer risk.UK funding includes Cancer Research UK and NIH.This is the final version of the article. It first appeared from BioMed Central via http://dx.doi.org/10.1186/s13058-016-0718-

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

Two truncating variants in FANCC and breast cancer risk

Fanconi anemia (FA) is a genetically heterogeneous disorder with 22 disease-causing genes reported to date. In some FA genes, monoallelic mutations have been found to be associated with breast cancer risk, while the risk associations of others remain unknown. The gene for FA type C, FANCC, has been proposed as a breast cancer susceptibility gene based on epidemiological and sequencing studies. We used the Oncoarray project to genotype two truncating FANCC variants (p.R185X and p.R548X) in 64,760 breast cancer cases and 49,793 controls of European descent. FANCC mutations were observed in 25 cases (14 with p.R185X, 11 with p.R548X) and 26 controls (18 with p.R185X, 8 with p.R548X). There was no evidence of an association with the risk of breast cancer, neither overall (odds ratio 0.77, 95% CI 0.44-1.33, p = 0.4) nor by histology, hormone receptor status, age or family history. We conclude that the breast cancer risk association of these two FANCC variants, if any, is much smaller than for BRCA1, BRCA2 or PALB2 mutations. If this applies to all truncating variants in FANCC it would suggest there are differences between FA genes in their roles on breast cancer risk and demonstrates the merit of large consortia for clarifying risk associations of rare variants.Peer reviewe

Enhancing resilience: Understanding the impact of flood hazard and vulnerability on business interruption and losses

Without taking additional measures, flooding is becoming more likely and intense in a changing climate, which causes large economic damage. Households and firms are directly impacted by physical flood damage, but further ripple effects on society occur through business disruptions. By using post-disaster survey data from the 2021 flood event in the Netherlands, this study adds to the literature on business interruption duration and losses after flooding. The current empirical literature on flood impacts on firms is often unable to distinguish separate effects for flooded and non-flooded firms and does not incorporate flood severity and the influence of risk reduction measures. Here, we use multivariate regression models to determine depth-duration functions that describe the relationship between flood hazard characteristics and business interruption duration. This relationship can be used to calibrate flood damage models that capture indirect firm impacts. The prediction of business interruption after flooding allows for differentiation in business interruption between firms within a flooded area, reducing the reliance of these macroeconomic models on restrictive assumptions. Our results indicate that a day of business interruption duration costs a firm on average 0.5 % of their annual revenue; an effect that is stronger for firms with a weaker connection to their region. Flood damage mitigation (FDM) measures taken at the building level do not significantly affect business interruption duration, although further research on this is required. Finally, quick damage compensation is found to reduce business interruption duration and thus revenue losses, calling for higher insurance uptake and rapid and streamlined post-disaster insurance and government compensation.Hydraulic Structures and Flood Ris

In-vivo validation of on-line and off-line geometric coronary measurements using insertion of stenosis phantoms in procine coronary arteries

Geometric coronary artery measurements with the Phillips Digital Cardiac Imaging System (DCI) and the Cardiovascular Angiography Analysis System (CAAS) were validated using percutaneous insertion of radiolucent stenosis phantoms in swine coronary arteries. Angiographic visualization of the stenosis lumens (phi 0.5, 0.7, 1.0, 1.4, 1.9 mm) was simultaneously recorded on DCI and cinefilm. The acquisition systems were calibrated by either the diameter of the guiding catheter (catheter CAL) or the isocenter method (isocenter CAL). Minimal luminal diameters (MLD) obtained with CAAS and DCI on 20 corresponding cineframes were compared with the true phantom diameters (PD). The accuracy of MLD measurements with the CAAS using isocenter CAL was -0.07mm, the precision 0.21 mm (r = 0.91; y = 0.30 + 0.79x; SEE = 0.19), with catheter CAL the accuracy was 0.09 mm, the precision 0.23 mm (r = 0.89; y = 0.19 + 0.74x; SEE = 0.19). The accuracy of MLD measurements using the DCI with isocenter CAL was 0.08 mm, the precision 0.15 min (r = 0.96; y = 0.08 + 0.86x; SEE = 0.14), with catheter CAL the accuracy was 0.18 mm, the precision 0.21 mm (r = 0.92; y = 0.09 + 0.76x; SEE = 0.17). DCI underestimated PD with isocenter CAL (p less than 0.05) and with catheter CAL (p less than 0.001). MLD can be measured with high accuracy, both applying on-line digital as well as off-line cineangiographic analysis. The results of digital measurements demonstrate high reliability of the new digital software package