Well Balanced Finite Volume Methods for Nearly Hydrostatic Flows

In numerical approximations of nearly hydrostatic flows, a proper representation of the dominant hydrostatic balance is of crucial importance: unbalanced truncation errors can induce unacceptable spurious motions, e.g., in dynamical cores of models for numerical weather prediction (NWP) in particular near steep topography. In this paper we develop a new strategy for the construction of discretizations that are “well-balanced” with respect to dominant hydrostatics. The classical idea of formulating the momentum balance in terms of deviations of pressure from a balanced background distribution is realized here through local, time dependent hydrostatic reconstructions. Balanced discretizations of the pressure gradient and of the gravitation source term are achieved through a “discrete Archimedes' buoyancy principle”. This strategy is applied to extend an explicit standard finite volume Godunov-type scheme for compressible flows with minimal modifications. The resulting method has the following features: (i) It inherits its conservation properties from the underlying base scheme. (ii) It is exactly balanced, even on curvilinear grids, for a large class of near-hydrostatic flows. (iii) It solves the full compressible flow equations without reference to a background state that is defined for an entire vertical column of air. (iv) It is robust with respect to details of the implementation, such as the choice of slope limiting functions, or the particularities of boundary condition discretizations

Modelling survival and connectivity of Mnemiopsis leidyi in the south-western North Sea and Scheldt estuaries

Three different models were applied to study the reproduction, survival and dispersal of Mnemiopsis leidyi in the Scheldt estuaries and the southern North Sea: a high-resolution particle tracking model with passive particles, a low-resolution particle tracking model with a reproduction model coupled to a biogeochemical model, and a dynamic energy budget (DEB) model. The results of the models, each with its strengths and weaknesses, suggest the following conceptual situation: (i) the estuaries possess enough retention capability to keep an overwintering population, and enough exchange with coastal waters of the North Sea to seed offshore populations; (ii) M. leidyi can survive in the North Sea, and be transported over considerable distances, thus facilitating connectivity between coastal embayments; (iii) under current climatic conditions, M. leidyi may not be able to reproduce in large numbers in coastal and offshore waters of the North Sea, but this may change with global warming; however, this result is subject to substantial uncertainty. Further quantitative observational work is needed on the effects of temperature, salinity and food availability on reproduction and on mortality at different life stages to improve models such as used here

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]

Experimental Evaluation of Ultrasonic Simulation Techniques in Anisotropic Material

The high performance of the available computer technology provides the possibility to simulate the real life for ultrasonic inspections in terms of primary ultrasonic data like rf-time signals. For isotropic material codes like Generalized Point Source Synthesis (GPSS) or Elastodynamic Finite Integration Technique (EFIT) and the theoretical predictions correlate well with experimental results. Recently, the codes mentioned above have been extended to operate also in anisotropic material. In a first step the codes GPSS and EFIT have been expanded to work in materials of parallel oriented columnar grain structure with transversely isotropic symmetry. In order to verify these codes a set of experiments was carried out on weld metal pads and on welds of defined grain structure. Radiation, propagation, reflexion on boundaries and interaction of the sound field with defects for the modes “through transmission” and “pulse echo” were simulated and compared with the experiment

Coordination-driven magnetic-to-nonmagnetic transition in manganese doped silicon clusters

The interaction of a single manganese impurity with silicon is analyzed in a combined experimental and theoretical study of the electronic, magnetic, and structural properties of manganese-doped silicon clusters. The structural transition from exohedral to endohedral doping coincides with a quenching of high-spin states. For all geometric structures investigated, we find a similar dependence of the magnetic moment on the manganese coordination number and nearest neighbor distance. This observation can be generalized to manganese point defects in bulk silicon, whose magnetic moments fall within the observed magnetic-to-nonmagnetic transition, and which therefore react very sensitively to changes in the local geometry. The results indicate that high spin states in manganese-doped silicon could be stabilized by an appropriate lattice expansion

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

Racial Differences in the Distribution of Posterior Circulation Occlusive Disease

We Compared Clinical and Arteriographic Features in 27 White and 24 Black Patients with Symptomatic Posterior Circulation Occlusive Disease. the Degree of Arterial Stenosis Was Measured Independently by Two Examiners at 12 Sites within the Vertebrobasilar Territory. Racial Comparisons Were Made based Upon the Distribution of Extra- and Intracranial Occlusive Lesions and Symptomatic Sites of the Lesions. White Patients Had Significantly More Angina Pectoris, More Lesions of the Origin of the Left Vertebral Artery and More High-Grade Lesions of the Extracranial Vertebral Arteries. Black Patients Had Significantly Higher Mean Diastolic Blood Pressure, More Diabetes Mellitus, More Lesions of the Distal Basilar Artery, More High-Grade Lesions of Intracranial Branch Vessels and More Symptomatic Intracranial Branch Disease. Race Was Found to Be the Only Factor Increasing the Risk of Intracranial Posterior Circulation Occlusive Disease. Knowledge of the Contribution of Race to the Distribution of Posterior Circulation Lesions Will Help Guide Evaluation and Treatment Strategies for Patients with Vertebrobasilar Occlusive Disease. © 1985 American Heart Association, Inc

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

Spin-phonon coupling in epitaxial Sr0.6Ba0.4MnO3 thin films

Spin-phonon coupling is investigated in epitaxially strained Sr1-xBaxMnO3 thin films with perovskite structure by means of microwave (MW) and infrared (IR) spectroscopy. In this work we focus on the Sr0.6Ba0.4MnO3 composition grown on (LaAlO3)0.3(Sr2AlTaO6)0.7 substrate. The MW complex electromagnetic response shows a decrease in the real part and a clear anomaly in the imaginary part around 150 K. Moreover, it coincides with a 17% hardening of the lowest-frequency polar phonon seen in IR reflectance spectra. In order to further elucidate this phenomenon, low-energy muon-spin spectroscopy was carried out, signaling the emergence of antiferromagnetic order with Néel temperature (TN) around 150 K. Thus, our results confirm that epitaxial Sr0.6Ba0.4MnO3 thin films display strong spin-phonon coupling below TN, which may stimulate further research on tuning the magnetoelectric coupling by controlling the epitaxial strain and chemical pressure in the Sr1-xBaxMnO3 system