Genome-wide association meta-analysis of single-nucleotide polymorphisms and symptomatic venous thromboembolism during therapy for acute lymphoblastic leukemia and lymphoma in caucasian children

Symptomatic venous thromboembolism (VTE) occurs in five percent of children treated for acute lymphoblastic leukemia (ALL), but whether a genetic predisposition exists across different ALL treatment regimens has not been well studied.MethodsWe undertook a genome-wide association study (GWAS) meta-analysis for VTE in consecutively treated children in the Nordic/Baltic acute lymphoblastic leukemia 2008 (ALL2008) cohort and the Australian Evaluation of Risk of ALL Treatment-Related Side-Effects (ERASE) cohort. A total of 92 cases and 1481 controls of European ancestry were included.ResultsNo SNPs reached genome-wide significance (p -8) in either cohort. Among the top 34 single-nucleotide polymorphisms (SNPs) (p -6), two loci had concordant effects in both cohorts: ALOX15B (rs1804772) (MAF: 1%; p = 3.95 × 10-7) that influences arachidonic acid metabolism and thus platelet aggregation, and KALRN (rs570684) (MAF: 1%; p = 4.34 × 10-7) that has been previously associated with risk of ischemic stroke, atherosclerosis, and early-onset coronary artery disease.ConclusionThis represents the largest GWAS meta-analysis conducted to date associating SNPs to VTE in children and adolescents treated on childhood ALL protocols. Validation of these findings is needed and may then lead to patient stratification for VTE preventive interventions. As VTE hemostasis involves multiple pathways, a more powerful GWAS is needed to detect combination of variants associated with VTE.Marion K. Mateos, Morten Tulstrup, Michael CJ Quinn, Ruta Tuckuviene, Glenn M. Marshall, Ramneek Gupt

Multilayer design of crN/MoN superhard protective coatings and their characterisation

Multilayer CrN/MoN transition metal nitride coatings were studied in this research. Films were deposited by vacuum arc deposition (Arc-PVD) from Cr and Mo cathodes in nitrogen atmosphere p = 0.4 Pa. Three series of samples with different values of negative bias voltage (−20, −150, and −300 V) applied to the surface were fabricated. Each series has samples with 11, 22, 44, 88, 180 and 354 layers while total thickness was maintained with the same value. Samples were studied by scanning electron microscopy (SEM) on cross-sections and coatings surface, energy-dispersive X-ray spectroscopy (EDS), electron backscatter diffraction (EBSD), high-resolution transmission electron microscopy (HRTEM), X-ray diffraction (XRD), micro-indentation. Two main cubic phases of γ-Mo N and cubic CrN were detected. It was observed that the crystal growth orientation changes while the negative bias voltage of the substrate decreases. The maximum values of hardness (38–42 GPa) among the studied samples were obtained for coatings with a minimal individual layer thickness of 20 nm deposited at U = −20 V. N 2 bFCT - Sumy State University(0116U002621). Foundation of Science and Technology (FCT) of Portugal [references NORTE-01- 0145-FEDER-022096, SFRH/BD/129614/2017], Network of Extreme Conditions Laboratories (NECL) and by Ukrainian state budget programs [No. 0116U006816, 0118U003579 and 0116U002621]. Partial support by COST Action CA15102 is also greatly appreciate