Adjoint-Based Error Estimation and Mesh Adaptation for Hybridized Discontinuous Galerkin Methods

We present a robust and efficient target-based mesh adaptation methodology, building on hybridized discontinuous Galerkin schemes for (nonlinear) convection-diffusion problems, including the compressible Euler and Navier-Stokes equations. Hybridization of finite element discretizations has the main advantage, that the resulting set of algebraic equations has globally coupled degrees of freedom only on the skeleton of the computational mesh. Consequently, solving for these degrees of freedom involves the solution of a potentially much smaller system. This not only reduces storage requirements, but also allows for a faster solution with iterative solvers. The mesh adaptation is driven by an error estimate obtained via a discrete adjoint approach. Furthermore, the computed target functional can be corrected with this error estimate to obtain an even more accurate value. The aim of this paper is twofold: Firstly, to show the superiority of adjoint-based mesh adaptation over uniform and residual-based mesh refinement, and secondly to investigate the efficiency of the global error estimate

meta-analytical evaluation of coronary CT angiography studies

Zielsetzung: Ziel der Arbeit ist es, zu bestimmen, ob die Benutzung einer Sechsfeldertafel mit einer Intention-to-Diagnose Herangehensweise sich zur transparenten Darstellung und zum Umgang mit nichtbeurteilbaren Ergebnissen bei der Beurteilung der diagnostischen Genauigkeit eines Testverfahrens besser eignet, als die Benutzung einer "klassischen" Vierfeldertafel. Studiendesign: Basierend auf einer systematischen Suche nach diagnostischen Genauigkeitsstudien zur CT Koronarangiografie wurden Volltexte relevanter Studien dahingehend untersucht, ob alternativ eine Sechsfeldertafel berechnet werden konnte. Um einen Gesamteffekt zu quantifizieren, wurden die diagnostischen Genauigkeitswerte gemäß einer metaanalytischen Methodik statistisch zusammengefasst (gepoolt). Datenquellen: Gesucht wurde in den elektronische Datenbanken Medline (via PubMed), Embase (via Ovid) und ISI Web of Science. Eignungskriterien: Prospektive Studien in Englisch oder Deutsch, die die CT Koronarangiografie mit der konventionellen Koronarangiografie (beide Verfahren bei allen Patienten durchgeführt) verglichen und adäquate Daten für eine Analyse auf Patientenebene lieferten. Ergebnisse: 120 Studien (mit 10.287 Patienten) wurden als relevant identifiziert. Die Studien unterschieden sich stark in ihrer Herangehensweise, mit nichtbeurteilbaren Ergebnissen zu verfahren. Wir fanden 26 Studien (mit 2298 Patienten), für die sowohl eine Vier- als auch eine zusätzliche Sechsfeldertafel berechnet werden konnte. Unter Benutzung eines bivariaten Random Effects Modells verglichen wir die Ergebnisse der Vierfeldertafel mit denen der Sechsfeldertafel und identifizierten statistisch signifikante Unterschiede für die gepoolte Sensitivität ((98,2 (95% Konfidenzintervall (KI) 96,7 bis 99,1) gegenüber 92,7 (88,5 bis 95,3)), die Fläche unter der Kurve (area under the curve) (0,99 (0,98 bis 1,00) gegenüber 0,93 (0,91 bis 0,95)), die positive Likelihood Ratio (9,1 (6,2 bis 13,3) gegenüber 4,4 (3,3 bis 6,0)) und die Negative Likelihood Ratio (0,02 (0,01 bis 0,04) gegenüber 0,09 (0,06 bis 0,15); (p<0,05)). Schlussfolgerung: Die Parameter der diagnostischen Wertigkeit nehmen signifikant ab, wenn nichtbeurteilbare Ergebnisse aus der Sechsfeldertafel mit in die Analyse einfließen (Intention-to-Diagnose Herangehensweise). Diese Herangehensweise liefert ein realistischeres Abbild der klinischen Wertigkeit diagnostischer Tests.Objective: To determine whether a 3×2 table, using an intention to diagnose approach, is better than the “classic” 2×2 table at handling transparent reporting and non-evaluable results, when assessing the accuracy of a diagnostic test. Design: Based on a systematic search for diagnostic accuracy studies of coronary computed tomography (CT) angiography, full texts of relevant studies were evaluated to determine whether they could calculate an alternative 3×2 table. To quantify an overall effect, we pooled diagnostic accuracy values according to a meta-analytical approach. Data sources: Medline (via PubMed), Embase (via Ovid), and ISI Web of Science electronic databases. Eligibility criteria: Prospective English or German language studies comparing coronary CT with conventional coronary angiography in all patients and providing sufficient data for a patient level analysis. Results: 120 studies (10,287 patients) were eligible. Studies varied greatly in their approaches to handling non-evaluable findings. We found 26 studies (including 2298 patients) that allowed us to calculate both 2×2 tables and 3×2 tables. Using a bivariate random effects model, we compared the 2×2 table with the 3×2 table, and found significant differences for pooled sensitivity (98.2 (95% confidence interval 96.7 to 99.1) v 92.7 (88.5 to 95.3)), area under the curve (0.99 (0.98 to 1.00) v 0.93 (0.91 to 0.95)), positive likelihood ratio (9.1 (6.2 to 13.3) v 4.4 (3.3 to 6.0)), and negative likelihood ratio (0.02 (0.01 to 0.04) v 0.09 (0.06 to 0.15); (P<0.05)). Conclusion: Parameters for diagnostic performance significantly decrease if non-evaluable results are included by a 3×2 table for analysis (intention to diagnose approach). This approach provides a more realistic picture of the clinical potential of diagnostic tests

A Comparison of Hybridized and Standard DG Methods for Target-Based hp-Adaptive Simulation of Compressible Flow

We present a comparison between hybridized and non-hybridized discontinuous Galerkin methods in the context of target-based hp-adaptation for compressible flow problems. The aim is to provide a critical assessment of the computational efficiency of hybridized DG methods. Hybridization of finite element discretizations has the main advantage, that the resulting set of algebraic equations has globally coupled degrees of freedom only on the skeleton of the computational mesh. Consequently, solving for these degrees of freedom involves the solution of a potentially much smaller system. This not only reduces storage requirements, but also allows for a faster solution with iterative solvers. Using a discrete-adjoint approach, sensitivities with respect to output functionals are computed to drive the adaptation. From the error distribution given by the adjoint-based error estimator, h- or p-refinement is chosen based on the smoothness of the solution which can be quantified by properly-chosen smoothness indicators. Numerical results are shown for subsonic, transonic, and supersonic flow around the NACA0012 airfoil. hp-adaptation proves to be superior to pure h-adaptation if discontinuous or singular flow features are involved. In all cases, a higher polynomial degree turns out to be beneficial. We show that for polynomial degree of approximation p=2 and higher, and for a broad range of test cases, HDG performs better than DG in terms of runtime and memory requirements

Vortex core switching by coherent excitation with single in-plane magnetic field pulses

The bistability of the core magnetization of nano-scaled magnets with a magnetic vortex configuration has great potential for data storage applications. To exploit this, reliable switching between the two possible states is needed. Time resolved x-ray microscopy was used to study the response of the vortex core to excitation pulses at sub-ns timescales and image the vortex core switching. A reliable switching process by coherent excitation with leading and trailing edges of in-plane magnetic field pulses was found and compared with micromagnetic simulations.Comment: 4 pages, 3 figure

Polarisation selective magnetic vortex dynamics and core reversal in rotating magnetic fields

A magnetic vortex occurs as an equilibrium configuration in thin ferromagnetic platelets of micron and sub-micron size and is characterised by an in-plane curling magnetisation. At the centre, a magnetic singularity is avoided by an out-of-plane magnetisation core. This core has a gyrotropic excitation mode, which corresponds to a circular motion of the vortex around its equilibrium position, where the rotation sense is determined by the direction of the vortex core magnetisation, its polarisation. Unlike linear fields or spin polarised currents, which excite both polarisation states, an in-plane rotating field can selectively excite one of the polarisation states. Here we report the observation of vortex dynamics in response to rotating magnetic fields, imaged with time-resolved scanning X-ray microscopy. We demonstrate that the rotating field only excites the gyrotropic mode if the rotation sense of the field coincides with the vortex gyration sense and that such a field can selectively reverse the vortex polarisation

Combination of computed tomography angiography with coronary artery calcium score for improved diagnosis of coronary artery disease: a collaborative meta-analysis of stable chest pain patients referred for invasive coronary angiography

OBJECTIVES: Coronary computed tomography angiography (CCTA) has higher diagnostic accuracy than coronary artery calcium (CAC) score for detecting obstructive coronary artery disease (CAD) in patients with stable chest pain, while the added diagnostic value of combining CCTA with CAC is unknown. We investigated whether combining coronary CCTA with CAC score can improve the diagnosis of obstructive CAD compared with CCTA alone. METHODS: A total of 2315 patients (858 women, 37%) aged 61.1 ± 10.2 from 29 original studies were included to build two CAD prediction models based on either CCTA alone or CCTA combined with the CAC score. CAD was defined as at least 50% coronary diameter stenosis on invasive coronary angiography. Models were built by using generalized linear mixed-effects models with a random intercept set for the original study. The two CAD prediction models were compared by the likelihood ratio test, while their diagnostic performance was compared using the area under the receiver-operating-characteristic curve (AUC). Net benefit (benefit of true positive versus harm of false positive) was assessed by decision curve analysis. RESULTS: CAD prevalence was 43.5% (1007/2315). Combining CCTA with CAC improved CAD diagnosis compared with CCTA alone (AUC: 87% [95% CI: 86 to 89%] vs. 80% [95% CI: 78 to 82%]; p < 0.001), likelihood ratio test 236.3, df: 1, p < 0.001, showing a higher net benefit across almost all threshold probabilities. CONCLUSION: Adding the CAC score to CCTA findings in patients with stable chest pain improves the diagnostic performance in detecting CAD and the net benefit compared with CCTA alone. CLINICAL RELEVANCE STATEMENT: CAC scoring CT performed before coronary CTA and included in the diagnostic model can improve obstructive CAD diagnosis, especially when CCTA is non-diagnostic. KEY POINTS: • The combination of coronary artery calcium with coronary computed tomography angiography showed significantly higher AUC (87%, 95% confidence interval [CI]: 86 to 89%) for diagnosis of coronary artery disease compared to coronary computed tomography angiography alone (80%, 95% CI: 78 to 82%, p < 0.001). • Diagnostic improvement was mostly seen in patients with non-diagnostic C. • The improvement in diagnostic performance and the net benefit was consistent across age groups, chest pain types, and genders

Multiple Myeloma Treatment in Real-world Clinical Practice : Results of a Prospective, Multinational, Noninterventional Study

Funding Information: The authors would like to thank all patients and their families and all the EMMOS investigators for their valuable contributions to the study. The authors would like to acknowledge Robert Olie for his significant contribution to the EMMOS study. Writing support during the development of our report was provided by Laura Mulcahy and Catherine Crookes of FireKite, an Ashfield company, a part of UDG Healthcare plc, which was funded by Millennium Pharmaceuticals, Inc, and Janssen Global Services, LLC. The EMMOS study was supported by research funding from Janssen Pharmaceutical NV and Millennium Pharmaceuticals, Inc. Funding Information: The authors would like to thank all patients and their families and all the EMMOS investigators for their valuable contributions to the study. The authors would like to acknowledge Robert Olie for his significant contribution to the EMMOS study. Writing support during the development of our report was provided by Laura Mulcahy and Catherine Crookes of FireKite, an Ashfield company, a part of UDG Healthcare plc, which was funded by Millennium Pharmaceuticals, Inc, and Janssen Global Services, LLC. The EMMOS study was supported by research funding from Janssen Pharmaceutical NV and Millennium Pharmaceuticals, Inc. Funding Information: M.M. has received personal fees from Janssen, Celgene, Amgen, Bristol-Myers Squibb, Sanofi, Novartis, and Takeda and grants from Janssen and Sanofi during the conduct of the study. E.T. has received grants from Janssen and personal fees from Janssen and Takeda during the conduct of the study, and grants from Amgen, Celgene/Genesis, personal fees from Amgen, Celgene/Genesis, Bristol-Myers Squibb, Novartis, and Glaxo-Smith Kline outside the submitted work. M.V.M. has received personal fees from Janssen, Celgene, Amgen, and Takeda outside the submitted work. M.C. reports honoraria from Janssen, outside the submitted work. M. B. reports grants from Janssen Cilag during the conduct of the study. M.D. has received honoraria for participation on advisory boards for Janssen, Celgene, Takeda, Amgen, and Novartis. H.S. has received honoraria from Janssen-Cilag, Celgene, Amgen, Bristol-Myers Squibb, Novartis, and Takeda outside the submitted work. V.P. reports personal fees from Janssen during the conduct of the study and grants, personal fees, and nonfinancial support from Amgen, grants and personal fees from Sanofi, and personal fees from Takeda outside the submitted work. W.W. has received personal fees and grants from Amgen, Celgene, Novartis, Roche, Takeda, Gilead, and Janssen and nonfinancial support from Roche outside the submitted work. J.S. reports grants and nonfinancial support from Janssen Pharmaceutical during the conduct of the study. V.L. reports funding from Janssen Global Services LLC during the conduct of the study and study support from Janssen-Cilag and Pharmion outside the submitted work. A.P. reports employment and shareholding of Janssen (Johnson & Johnson) during the conduct of the study. C.C. reports employment at Janssen-Cilag during the conduct of the study. C.F. reports employment at Janssen Research and Development during the conduct of the study. F.T.B. reports employment at Janssen-Cilag during the conduct of the study. The remaining authors have stated that they have no conflicts of interest. Publisher Copyright: © 2018 The AuthorsMultiple myeloma (MM) remains an incurable disease, with little information available on its management in real-world clinical practice. The results of the present prospective, noninterventional observational study revealed great diversity in the treatment regimens used to treat MM. Our results also provide data to inform health economic, pharmacoepidemiologic, and outcomes research, providing a framework for the design of protocols to improve the outcomes of patients with MM. Background: The present prospective, multinational, noninterventional study aimed to document and describe real-world treatment regimens and disease progression in multiple myeloma (MM) patients. Patients and Methods: Adult patients initiating any new MM therapy from October 2010 to October 2012 were eligible. A multistage patient/site recruitment model was applied to minimize the selection bias; enrollment was stratified by country, region, and practice type. The patient medical and disease features, treatment history, and remission status were recorded at baseline, and prospective data on treatment, efficacy, and safety were collected electronically every 3 months. Results: A total of 2358 patients were enrolled. Of these patients, 775 and 1583 did and did not undergo stem cell transplantation (SCT) at any time during treatment, respectively. Of the patients in the SCT and non-SCT groups, 49%, 21%, 14%, and 15% and 57%, 20%, 12% and 10% were enrolled at treatment line 1, 2, 3, and ≥ 4, respectively. In the SCT and non-SCT groups, 45% and 54% of the patients had received bortezomib-based therapy without thalidomide/lenalidomide, 12% and 18% had received thalidomide/lenalidomide-based therapy without bortezomib, and 30% and 4% had received bortezomib plus thalidomide/lenalidomide-based therapy as frontline treatment, respectively. The corresponding proportions of SCT and non-SCT patients in lines 2, 3, and ≥ 4 were 45% and 37%, 30% and 37%, and 12% and 3%, 33% and 27%, 35% and 32%, and 8% and 2%, and 27% and 27%, 27% and 23%, and 6% and 4%, respectively. In the SCT and non-SCT patients, the overall response rate was 86% to 97% and 64% to 85% in line 1, 74% to 78% and 59% to 68% in line 2, 55% to 83% and 48% to 60% in line 3, and 49% to 65% and 36% and 45% in line 4, respectively, for regimens that included bortezomib and/or thalidomide/lenalidomide. Conclusion: The results of our prospective study have revealed great diversity in the treatment regimens used to manage MM in real-life practice. This diversity was linked to factors such as novel agent accessibility and evolving treatment recommendations. Our results provide insight into associated clinical benefits.publishersversionPeer reviewe

Ex Practica Philosophia de Fortitudine

Duce Deo & Praeside M. Michaele Wendelero Schlettano, Alum. Electorali & Facult. Philos. Adiuncto, publice disputabit Georgius Jacobus Schütze Noricus die 26. Iunii in Auditorio Minori horis matutini