Understanding the availability of wind turbines (WT) is vital to maximize WT energy production and minimize the capital payback period. Previous work on this subject concentrated on reliability and the location of WT failure modes rather than root causes. This paper concentrates on the influence of weather and WT location on failure rate and downtime, to try to understand root causes and the consequences of failure. The paper goes further than a previous study, which used Windstats data from the whole of Denmark, by considering a limited population of identical WTs at three locations on the German Nordzee, Ostzee and in western Germany, using data from WMEP and local weather stations. This new study focuses more precisely than the previous study by using more reliable data. The data were analysed to find the WT failures and weather conditions and then cross-correlate them. To confirm their representativeness, the reliability characteristics of these smaller WT populatio ns followed the average trends of the overall WMEP survey. However, clear differences were observed in the failure behaviour of the WTs at the three locations. Annual periodicity was seen in the weather data, as expected, but not in individual WT population failure data. However, clear cross-correlations can be seen between WT failures and weather data, in particular wind speed, maximum temperature and humidity. These cross-correlations were more convincing than those found in the earlier, larger Danish study, vindicating the more focused approach. It is also clear from the analysis that Operation & Maintenance also has an impact on WT failure rates. These factors will be important for the operation of offshore WTs with the work indicating how weather conditions may affect offshore WT failure rates

EssentialsAntithrombin Budapest3 (ATBp3; p.Leu131Phe) causing heparin-binding-site defect is common. We studied the clinical and laboratory phenotype of a large Hungarian ATBp3 cohort (n = 102). Founder effect of ATBp3 was confirmed by 12 genetic markers; anti-FXa AT assay was 100% sensitive. The spectrum of thrombotic symptoms was wide in ATBp3 patients including arterial thrombosis.Summary. Background: Antithrombin (AT) is a key regulator of the coagulation. In type II deficiency, the heparinbinding-site defect (type II HBS) is considered to be relatively low thrombosis risk. Objectives: Our aims were to search for SERPINC1 mutation(s) and to describe the clinical and laboratory phenotype of a large number of AT Budapest3 (ATBp3, p.Leu131Phe) carriers and confirm the presence of a founder effect. Patients/Methods: AT-deficient patients were recruited and carriers of ATBp3, n = 102 (63 families) were selected. To investigate the founder effect, eight intragenic single nucleotide polymorphisms, a 5 0 -length dimorphism, and five microsatellite markers were detected. Clinical and laboratory data of the patients were collected and analyzed. Results: In AT deficiency, 16 different causative mutations were found, and the great majority of patients were of type II HBS subtype. Most of them (n = 102/118, 86.5%) carried the ATBp3 mutation. The ATBp3 mutant allele was associated with one single haplotype, while different haplotypes were detected in the case of normal allele. The anti-factor Xabased AT activity assay that we used could detect all ATBp3 patients with high sensitivity in our cohort. ATBp3 homozygosity (n = 26) was associated with thrombosis at a young age and conferred a high thrombotic risk. Half of the heterozygotes (n = 41/76, 53.9%) also had venous and/ or arterial thrombosis, and pregnancy complications were also recorded. Conclusion: In Hungary, the founder mutation, ATBp3, is the most common AT deficiency. Our study is the first in which the clinical characterization of ATBp3 mutation was executed in a large population.

Introduction: Inherited antithrombin (AT) deficiency is a heterogeneous disease. Due to low prevalence, only a few studies are available concerning genotype-phenotype associations. The aim was to describe the clinical, laboratory and genetic characteristics of AT deficiency in a large cohort including children and to add further laboratory data on the different sensitivity of functional AT assays.Patients and methods: Non-related AT deficient patients (n=156) and their family members (total n=246) were recruited. Clinical and laboratory data were collected, the mutation spectrum of SERPINC1 was described. Three different AT functional assays were explored.Results: Thirty-one SERPINC1 mutations including 11 novel ones and high mutation detection rate (98%) were detected. Heparin binding site deficiency (type IIHBS) was the most frequent (75.6%) including AT Budapest3 (ATBp3), AT Padua I and AT Basel (86%, 9% and 4% of type IIHBS, respectively). Clinical and laboratory phenotypes of IIHBS were heterogeneous and dependent on the specific mutation.Arterial thrombosis and pregnancy complications were the most frequent in AT Basel and AT Padua I, respectively. Median age at the time of thrombosis was the lowest in

Anti-FXa antithrombin assay is recommended as a first-line test to detect type II heparin-binding site antithrombin deficiency.

Antithrombin (AT) is a serine protease inhibitor, its activity is highly accelerated by heparin. Mutations at the heparin-binding region lead to functional defect, type II heparin-binding site (IIHBS) AT deficiency. The aim of this study was to investigate and compare the molecular background of AT Budapest 3 (p.Leu131Phe, ATBp3), AT Basel (p.Pro73Leu), and AT Padua (p.Arg79His) mutations. Advanced in silico methods and heparin-binding studies of recombinant AT proteins using surface plasmon resonance method were used. Crossed immunoelectrophoresis and Differential Scanning Fluorimetry (NanoDSF) were performed in plasma samples. Heparin affinity of AT Padua was the lowest (KD = 1.08 × 10−6 M) and had the most severe consequences affecting the allosteric pathways of activation, moreover significant destabilizing effects on AT were also observed. KD values for AT Basel, ATBp3 and wild-type AT were 7.64 × 10−7 M, 2.15 × 10−8 M and 6.4 × 10−10 M, respectively. Heparin-binding of AT Basel was slower, however once the complex was formed the mutation had only minor effect on the secondary and tertiary structures. Allosteric activation of ATBp3 was altered, moreover decreased thermostability in ATBp3 homozygous plasma and increased fluctuations in multiple regions of ATBp3 were observed by in silico methods suggesting the presence of a quantitative component in the pathogenicity of this mutation due to molecular instability.