Multi-barrier cleavage models consider cleavage fracture which is characterized by a series of microscale events. One of the challenges for multi-barrier cleavage models is the strong variations of cleavage parameters across different types of steels. The source and magnitude of the variations have not been studied systematically. In the current paper, cleavage parameters corresponding to fracture initiation at a hard particle and crack propagation overcoming grain boundaries are determined for three bainitic steels, a martensitic steel, and a ferritic steel, using a recently proposed model. It is found that the particle fracture parameter depends on particle morphology and composition, while the grain boundary cleavage parameter depends on the hierarchical grain structure. The determined values of cleavage parameters present a high degree of consistency among the five different steels, which allows the further application on microstructure design to control macroscopic toughness.

Offshore wind energy development (OWED) is rapidly expanding globally and has the potential to contribute significantly to renewable energy portfolios. However, development of infrastructure in the marine environment presents risks to wildlife. Marine birds in particular have life history traits that amplify population impacts from displacement and collision with offshore wind infrastructure. Here, we present a broadly applicable framework to assess and mitigate the impacts of OWED on marine birds. We outline existing techniques to quantify impact via monitoring and modeling (e.g., collision risk models, population viability analysis), and present a robust mitigation framework to avoid, minimize, or compensate for OWED impacts. Our framework addresses impacts within the context of multiple stressors across multiple wind energy developments. We also present technological and methodological approaches that can improve impact estimation and mitigation. We highlight compensatory mitigation as a tool that can be incorporated into regulatory frameworks to mitigate impacts that cannot be avoided or minimized via siting decisions or alterations to OWED infrastructure or operation. Our framework is intended as a globally-relevant approach for assessing and mitigating OWED impacts on marine birds that may be adapted to existing regulatory frameworks in regions with existing or planned OWED.

For structural assessment and optimal design of thick-section high-strength steels in applications under harsh service conditions, it is essential to understand the cleavage fracture micromechanisms. In this study, we assess the effects of through-thickness microstructure of an 80-mm-thick quenched and tempered S690 high-strength steel, notch orientation, and crack tip constraint in cleavage nucleation and propagation via sub-sized crack tip opening displacement (CTOD) testing at −100 °C. The notch was placed parallel and perpendicular to the rolling direction, and the crack tip constraint was analysed by varying the a/W ratio: 0.5, 0.25, and 0.1. The notch orientation does not play a role, and the material is considered isotropic in-plane. Nb-rich inclusions were observed to act as the weak microstructural link in the steel, triggering fracture in specimens with the lowest CTOD values. While shallow-cracked specimens from the top section present larger critical CTOD values than deep-cracked ones due to stress relief ahead of the crack tip, the constraint does not have a significant influence in the middle due to the very detrimental microstructure in the presence of Nb-rich inclusions. Some specimens show areas of intergranular fracture due to the combined effect of C, Cr, Mn, Ni, and P segregation along with precipitation of Nb-rich inclusions clusters on the grain boundaries. Several crack deflections at high-angle grain boundaries were observed where the neighbouring sub-structure has different Bain axes.

Introduction. The advantages of fixed-dose combination losartan + amlodipine + rosuvastatin compared to mono-drugs and two-component combinations are to increase the therapeutic efficacy, to reduce the cost of the product and to make the drug easier to take which helps to improve patient adherence to therapy. A bioequivalence study of the three-component fixed-dose combinations Losartan + amlodipine + rosuvastatin Sanofi with coadministered Lozap® AM (Losartan+Amlodipine) and Crestor® (Rosuvastatin) was conducted. Aim. The purpose of the bioequivalence trial was a comparative study of the pharmacokinetics and evidence of the bioequivalence of two strengths of fixed-dose combination: 1) Losartan + amlodipine + rosuvastatin Sanofi (tablets, 50 mg + 5 mg + 10 mg) in comparison with coadministrated drugs Lozap® AM (losartan + amlodipine, tablets, 50 mg + 5 mg,) and Crestor® (rosuvastatin, tablets, 10 mg) in fasting healthy volunteers after a single administration; 2) Losartan + amlodipine + rosuvastatin Sanofi (tablets, 100 mg + 5 mg + 20 mg) in comparison with coadministrated drugs Lozap® AM (losartan + amlodipine, tablets, 100 mg + 5 mg) and Crestor® (rosuvastatin, tablets, 20 mg) in fasting healthy volunteers 18–45 years old after a single dose. Materials and methods. To prove bioequivalence, an open label, comparative, randomized, crossover four-period clinical trial was conducted for each strengths of fixed-dose combination. The concentrations of losartan, amlodipine and rosuvastatin in blood plasma samples obtained from volunteers were determined by a validated HPLC-MS/MS method. A pharmacokinetic and statistical analysis was performed and confidence intervals (CI) for the pharmacokinetic parameters Сmax, AUC0-72 (for amlodipine) and AUC0-t (for losartan and rosuvastatin) were calculated. Results and discussion. Based on the results of statistical and pharmacokinetic analysis, it was shown that the studied formulations are bioequivalent in terms of pharmacokinetic parameters of losartan, amlodipine and rosuvastatin. 90 % CI were in the acceptable range for Сmax (of amlodipine), AUC0-72 (of amlodipine) and AUC0-t (of losartan and rosuvastatin). 90 % CI for Сmax of losartan and rosuvastatin were in the acceptable extended calculated range according to the protocol. Conclusion. Thus, according to the criteria used in the studies, the three-component fixed-dose combinations Losartan + amlodipine + rosuvastatin Sanofi are proved to be bioequivalent in comparison with coadministered Lozap® AM and Crestor®.

The through-thickness heterogeneous microstructure of thick-section high strength steels is responsible for the significant scatter of properties along the thickness. In this study, in order to identify the critical microstructural features in the fracture behaviour and allow for design optimisation and prediction of structural failure, the through-thickness microstructure of thick-section steels was extensively characterised and quantified. For this purpose, samples were extracted from the top quarter and middle thickness positions, and a combination of techniques including chemical composition analysis, dilatometry, and microscopy was used. The hardness variation through the thickness was analysed via micro-Vickers measurements and the local hardness variation in the middle section was studied via nanoindentation. The middle section presented larger prior austenite grain (PAG) sizes and larger sizes and area fraction of inclusions than the top section. Additionally, cubic inclusions were observed distributed as clusters in the middle, sometimes decorating PAG boundaries. Defects associated with the cubic inclusions or the interface between the matrix and the circular and cubic inclusions were observed in the mid-thickness. Moreover, the middle section presented long interfaces with the most significant hardness gradients due to the presence of hard centreline segregation bands. Hence, the microstructural and nanoindentation analyses indicated the middle section as the most likely area to have the lowest fracture toughness and, therefore, the most unfavourable section for fracture performance of the investigated S690QL high strength steel. The detrimental effect of the middle section was confirmed via CTOD tests where the middle presents lower fracture toughness than the top section.

The current research studies the coupled combustion inside the furnace and the steam generation inside the radiant and convection tubes through a typical Once-Through Steam Generator (OTSG). A 3-D CFD model coupling the combustion and the two-phase flow was developed to model the entire system of OTSG. Once the combustion simulation was converged, the results were compared to field data showing a convincing agreement. The CFD analysis provides the detailed flow behavior inside the combustion chamber and the stack, as well as the two-phase flow steam generation process in the radiant and convective sections. The flame shape and orientation, the velocity, the species, and the temperature distribution at the various parts of the furnace, as well as the steam generation and the steam distribution inside the pipes were investigated using the developed CFD model

AbstractSmall and medium enterprises (SME) are crucial for economy and have a higher exposure rate to default than large corporates. In this work, we address the problem of predicting the default of an SME. Default prediction models typically only consider the previous financial situation of each analysed company. Thus, they do not take into account the interactions between companies, which could be insightful as SMEs live in a supply chain ecosystem in which they constantly do business with each other. Thereby, we present a novel method to improve traditional default prediction models by incorporating information about the insolvency situation of customers and suppliers of a given SME, using a graph-based representation of SME supply chains. We analyze its performance and illustrate how this proposed solution outperforms the traditional default prediction approaches.KeywordsDefault predictionTransactional networkNetwork featuresNetwork-based modelsNetwork centrality

Macroscale cleavage fracture toughness of high strength steels is strongly related to the fracture of hard microstructural inclusions. Therefore, an accurate determination of the local stress on these inclusions based on the matrix stress is necessary for the statistical modelling of macroscale cleavage fracture. This paper presents analytical equations to quantitatively estimate the stress of the microstructural inclusions from the far-field stress of the matrix. The analytical equations account for the inclusion shape, the inclusion orientation, the far-field stress state and matrix material properties. Finite element modelling of a representative volume element containing a hard inclusion shows that the equations provide an accurate representation of the local stress state. The equations are implemented into a multi-barrier model and compared with CTOD experiments with two different levels of constraint.

Introduction. A fixed dose combination of telmisartan and amlodipine is widely used in clinical practice during hypertension treatment. Combination of telmisartan and amlodipine demonstrates potentiating synergistic effect on blood pressure decrease. A bioequivalence study of Telzap® AM with coadministered Mikardis® and Norvask® was conducted with 60 volunteers.Aim. The purpose of the bioequivalence trial was a comparative study of the pharmacokinetics and evidence of the bioequivalence of the fixed dose combination drug product Telzap® AM (telmisartan + amlodipine, tablets, 80 + 10 mg, Zentiva ks company, Czech Republic) and coadministrated monocomponent drug products Mikardis® (telmisartan, tablets 80 mg, Beringer Ingelheim International GmbH, Germany) and Norvask® [amlodipine, tablets 10 mg, Pfizer HCP Corporation (USA), Russia] in healthy volunteers after a single administration under fasting.Materials and methods. To prove bioequivalence, an open label, comparative, randomized, crossover four-period replicate clinical trial was conducted. The concentrations of amlodipine and telmisartan in plasma samples were determined by a validated HPLC-MS/MS method. A pharmacokinetic and statistical analysis was performed and confidence intervals for the pharmacokinetic parameters Cmax and AUC0-72 were calculated.Results and discussion. It can be concluded that the studied formulations are bioequivalent in terms of pharmacokinetic parameters of amlodipine and telmisartan. All 90 % confidence intervals for the estimated pharmacokinetic parameters of amlodipine were in the range of 80–125 %, 90 % confidence intervals for telmisartan were within the bioequivalence range of 80–125 % for AUC0-72, and 76.73–130.32 % for Cmax.Conclusion. Thus, according to the criteria used in the study, the formulations are proved to be bioequivalent.