Reconstruction of Defect Geometries in Ultrasonic NDT

The international activities in developing new flaw characterization methods with special emphasis on acoustic imaging have been increased. To reduce the dependency upon amplitude information and due to the fact that flaw information is buried in the shape and fine structure of wave fronts, considerable attention has been given to the development of methods using time-of-flight information from different probe positions. For this reason, with mechanical scanners and specially build data acquisition and evaluation systems, a vareity of ways to produce images has been developed. These include echotomography, linear or two dimensional mono- or multi-frequency holography, tip echo interference methods, ALOK (amplitude-,time-of-flight-locus curves), Phased Array, SAFT or Rayleigh-Sommerfeld Holography. These methods use mathematical algorithms which seem to be independent or which have been derived heuristically. Based upon the concept of elastodynamic diffraction theory together with that of tomography a concept can be derived which reveals the inner connection of these algorithms. Differences in the reconstructions arise due to limitations like limited aperture, limited bandwidth, use of mode converted signals or due to complex surface shapes. An attempt is made to cover the theoretical background, to give an overview on existing data acquisition systems and to describe the strength, weaknesses, and difficulties in producing acoustic images

Elastic Wave Propagation and Scattering in Austenitic Steel

Ultrasonic nondestructive testing of austenitic steel welds is very difficult, because fundamental wave propagation and scattering effects in such complicated anisotropic environments are only hardly understood [1, 2]. Therefore, a step-by-step evaluation of elastic wave propagation in transversely isotropic media has been initiated. Under the assumption of transverse isotropy the numerical EFIT code (Elastodynamic Finite Integration Technique) [3] - [7] was extended to anisotropic homogeneous media. It allows 3D computation of quasi pressure and quasi shear as well as surface waves in transverse isotropic media. Results for finite aperture transducer radiation and crack scattering in a single crystal austenitic weld are presented; measurements of amplitude dynamics, A-Scans and C-Scans confirm the EFIT simulations [8]

Overview of core impurity transport in the first divertor operation of Wendelstein 7-X

The impurity transport at Wendelstein 7-X during its most recent campaign is characterized and documented for a variety of different plasma scenarios. An overview of its dependence on several quantities is given, which allows identification of transport regimes and the major driver for impurity transport. Beyond this, a comparison with the impurity behavior in other fusion devices is now possible. In contrast to other stellarators, no density dependence of the impurity transport has been found. Additionally, the influence of the turbulence contribution to the overall transport is reflected in the dependence on various parameters, e.g. turbulent diffusion and density fluctuation amplitudes. With this database approach, one can now also apply scaling laws to make extrapolations about the impurity confinement in future plasma scenarios

A Systematic Review of Biomarkers and Risk of Incident Type 2 Diabetes: An Overview of Epidemiological, Prediction and Aetiological Research Literature

$\textbf{BACKGROUND}$ Blood-based or urinary biomarkers may play a role in quantifying the future risk of type 2 diabetes (T2D) and in understanding possible aetiological pathways to disease. However, no systematic review has been conducted that has identified and provided an overview of available biomarkers for incident T2D. We aimed to systematically review the associations of biomarkers with risk of developing T2D and to highlight evidence gaps in the existing literature regarding the predictive and aetiological value of these biomarkers and to direct future research in this field. $\textbf{METHODS AND FINDINGS}$ We systematically searched PubMed MEDLINE (January 2000 until March 2015) and Embase (until January 2016) databases for observational studies of biomarkers and incident T2D according to the 2009 PRISMA guidelines. We also searched availability of meta-analyses, Mendelian randomisation and prediction research for the identified biomarkers. We reviewed 3910 titles (705 abstracts) and 164 full papers and included 139 papers from 69 cohort studies that described the prospective relationships between 167 blood-based or urinary biomarkers and incident T2D. Only 35 biomarkers were reported in large scale studies with more than 1000 T2D cases, and thus the evidence for association was inconclusive for the majority of biomarkers. Fourteen biomarkers have been investigated using Mendelian randomisation approaches. Only for one biomarker was there strong observational evidence of association and evidence from genetic association studies that was compatible with an underlying causal association. In additional search for T2D prediction, we found only half of biomarkers were examined with formal evidence of predictive value for a minority of these biomarkers. Most biomarkers did not enhance the strength of prediction, but the strongest evidence for prediction was for biomarkers that quantify measures of glycaemia. $\textbf{CONCLUSIONS}$ This study presents an extensive review of the current state of the literature to inform the strategy for future interrogation of existing and newly described biomarkers for T2D. Many biomarkers have been reported to be associated with the risk of developing T2D. The evidence of their value in adding to understanding of causal pathways to disease is very limited so far. The utility of most biomarkers remains largely unknown in clinical prediction. Future research should focus on providing good genetic instruments across consortia for possible biomarkers in Mendelian randomisation, prioritising biomarkers for measurement in large-scale cohort studies and examining predictive utility of biomarkers for a given context.This study was supported by the Medical Research Council UK (grant reference no. MC_UU_12015/1), http://gtr.rcuk.ac.uk/projects?ref=MC_UU_12015/1; Netherlands Organization for Scientific Research (NWO project number 825.13.004), http://www.nwo.nl/en/research-and-results/research-projects/i/85/10585.html; Innovative Medicines Initiative Joint Undertaking under EMIF grant agreement no. 115372, resources of which are composed of financial contributions from the European Union's Seventh Framework Programme (FP7/2007-2013), http://www.emif.eu/about. GSK provided support in the form of salaries for DW, DJN, AS. Pfizer provided support in the form of salary to JMB

Implementation of paediatric precision oncology into clinical practice: The Individualized Therapies for Children with cancer program 'iTHER'

iTHER is a Dutch prospective national precision oncology program aiming to define tumour molecular profiles in children and adolescents with primary very high-risk, relapsed, or refractory paediatric tumours. Between April 2017 and April 2021, 302 samples from 253 patients were included. Comprehensive molecular profiling including low-coverage whole genome sequencing (lcWGS), whole exome sequencing (WES), RNA sequencing (RNA-seq), Affymetrix, and/or 850k methylation profiling was successfully performed for 226 samples with at least 20% tumour content. Germline pathogenic variants were identified in 16% of patients (35/219), of which 22 variants were judged causative for a cancer predisposition syndrome. At least one somatic alteration was detected in 204 (90.3%), and 185 (81.9%) were considered druggable, with clinical priority very high (6.1%), high (21.3%), moderate (26.0%), intermediate (36.1%), and borderline (10.5%) priority. iTHER led to revision or refinement of diagnosis in 8 patients (3.5%). Temporal heterogeneity was observed in paired samples of 15 patients, indicating the value of sequential analyses. Of 137 patients with follow-up beyond twelve months, 21 molecularly matched treatments were applied in 19 patients (13.9%), with clinical benefit in few. Most relevant barriers to not applying targeted therapies included poor performance status, as well as limited access to drugs within clinical trial. iTHER demonstrates the feasibility of comprehensive molecular profiling across all ages, tumour types and stages in paediatric cancers, informing of diagnostic, prognostic, and targetable alterations as well as reportable germline variants. Therefore, WES and RNA-seq is nowadays standard clinical care at the Princess Máxima Center for all children with cancer, including patients at primary diagnosis. Improved access to innovative treatments within biology-driven combination trials is required to ultimately improve survival. Keywords: Adolescent; Cancer; Child; Hereditary; Molecular biology; Molecular targeted therapy; Next-generation sequencing; Precision medicin

Strain-Engineered Ferroelastic Structures in PbTiO3 Films and Their Control by Electric Fields

We study the interplay between epitaxial strain, film thickness, and electric field in the creation, modification, and design of distinct ferroelastic structures in PbTiO thin films. Strain and thickness greatly affect the structures formed, providing a two-variable parameterization of the resulting self-assembly. Under applied electric fields, these strain-engineered ferroelastic structures are highly malleable, especially when a/c and a/a superdomains coexist. To reconfigure the ferroelastic structures and achieve self-assembled nanoscale-ordered morphologies, pure ferroelectric switching of individual c-domains within the a/c superdomains is essential. The stability, however, of the electrically written ferroelastic structures is in most cases ephemeral; the speed of the relaxation process depends sensitively on strain and thickness. Only under low tensile strain - as is the case for PbTiO on GdScO - and below a critical thickness do the electrically created a/c superdomain structures become stable for days or longer, making them relevant for reconfigurable nanoscale electronics or nonvolatile electromechanical applications

Type 2 diabetes and incidence of cardiovascular diseases: a cohort study in 1·9 million people.

BACKGROUND: The contemporary associations of type 2 diabetes with a wide range of incident cardiovascular diseases have not been compared. We aimed to study associations between type 2 diabetes and 12 initial manifestations of cardiovascular disease. METHODS: We used linked primary care, hospital admission, disease registry, and death certificate records from the CALIBER programme, which links data for people in England recorded in four electronic health data sources. We included people who were (or turned) 30 years or older between Jan 1, 1998, to March 25, 2010, who were free from cardiovascular disease at baseline. The primary endpoint was the first record of one of 12 cardiovascular presentations in any of the data sources. We compared cumulative incidence curves for the initial presentation of cardiovascular disease and used Cox models to estimate cause-specific hazard ratios (HRs). This study is registered at ClinicalTrials.gov (NCT01804439). FINDINGS: Our cohort consisted of 1 921 260 individuals, of whom 1 887 062 (98·2%) did not have diabetes and 34 198 (1·8%) had type 2 diabetes. We observed 113 638 first presentations of cardiovascular disease during a median follow-up of 5·5 years (IQR 2·1-10·1). Of people with type 2 diabetes, 6137 (17·9%) had a first cardiovascular presentation, the most common of which were peripheral arterial disease (reported in 992 [16·2%] of 6137 patients) and heart failure (866 [14·1%] of 6137 patients). Type 2 diabetes was positively associated with peripheral arterial disease (adjusted HR 2·98 [95% CI 2·76-3·22]), ischaemic stroke (1·72 [1·52-1·95]), stable angina (1·62 [1·49-1·77]), heart failure (1·56 [1·45-1·69]), and non-fatal myocardial infarction (1·54 [1·42-1·67]), but was inversely associated with abdominal aortic aneurysm (0·46 [0·35-0·59]) and subarachnoid haemorrhage (0·48 [0·26-0.89]), and not associated with arrhythmia or sudden cardiac death (0·95 [0·76-1·19]). INTERPRETATION: Heart failure and peripheral arterial disease are the most common initial manifestations of cardiovascular disease in type 2 diabetes. The differences between relative risks of different cardiovascular diseases in patients with type 2 diabetes have implications for clinical risk assessment and trial design. FUNDING: Wellcome Trust, National Institute for Health Research, and Medical Research Council

Механізми пересування мостових кранів

В роботі вирішена актуальна наукова задача, яка складається в обґрунтуванні нової конструкції кранового ходового колеса і розробці методики його розрахунку з урахуванням пружної вставки, що дозволяє значно зменшити динамічні навантаження при пересуванні вантажного візка і мосту крана. Для наукових та науково-педагогічних працівників, докторантів, аспірантів (ад'юнктів), здобувачів вищої освіти в межах навчальної програми технічного вузу IV рівня акредитації