24 research outputs found
Solving Forward and Inverse Problems of Contact Mechanics using Physics-Informed Neural Networks
This paper explores the ability of physics-informed neural networks (PINNs)
to solve forward and inverse problems of contact mechanics for small
deformation elasticity. We deploy PINNs in a mixed-variable formulation
enhanced by output transformation to enforce Dirichlet and Neumann boundary
conditions as hard constraints. Inequality constraints of contact problems,
namely Karush-Kuhn-Tucker (KKT) type conditions, are enforced as soft
constraints by incorporating them into the loss function during network
training. To formulate the loss function contribution of KKT constraints,
existing approaches applied to elastoplasticity problems are investigated and
we explore a nonlinear complementarity problem (NCP) function, namely
Fischer-Burmeister, which possesses advantageous characteristics in terms of
optimization. Based on the Hertzian contact problem, we show that PINNs can
serve as pure partial differential equation (PDE) solver, as data-enhanced
forward model, as inverse solver for parameter identification, and as
fast-to-evaluate surrogate model. Furthermore, we demonstrate the importance of
choosing proper hyperparameters, e.g. loss weights, and a combination of Adam
and L-BFGS-B optimizers aiming for better results in terms of accuracy and
training time
Impact of primary kidney disease on the effects of empagliflozin in patients with chronic kidney disease: secondary analyses of the EMPA-KIDNEY trial
Background: The EMPA KIDNEY trial showed that empagliflozin reduced the risk of the primary composite outcome of kidney disease progression or cardiovascular death in patients with chronic kidney disease mainly through slowing progression. We aimed to assess how effects of empagliflozin might differ by primary kidney disease across its broad population. Methods: EMPA-KIDNEY, a randomised, controlled, phase 3 trial, was conducted at 241 centres in eight countries (Canada, China, Germany, Italy, Japan, Malaysia, the UK, and the USA). Patients were eligible if their estimated glomerular filtration rate (eGFR) was 20 to less than 45 mL/min per 1·73 m2, or 45 to less than 90 mL/min per 1·73 m2 with a urinary albumin-to-creatinine ratio (uACR) of 200 mg/g or higher at screening. They were randomly assigned (1:1) to 10 mg oral empagliflozin once daily or matching placebo. Effects on kidney disease progression (defined as a sustained ≥40% eGFR decline from randomisation, end-stage kidney disease, a sustained eGFR below 10 mL/min per 1·73 m2, or death from kidney failure) were assessed using prespecified Cox models, and eGFR slope analyses used shared parameter models. Subgroup comparisons were performed by including relevant interaction terms in models. EMPA-KIDNEY is registered with ClinicalTrials.gov, NCT03594110. Findings: Between May 15, 2019, and April 16, 2021, 6609 participants were randomly assigned and followed up for a median of 2·0 years (IQR 1·5–2·4). Prespecified subgroupings by primary kidney disease included 2057 (31·1%) participants with diabetic kidney disease, 1669 (25·3%) with glomerular disease, 1445 (21·9%) with hypertensive or renovascular disease, and 1438 (21·8%) with other or unknown causes. Kidney disease progression occurred in 384 (11·6%) of 3304 patients in the empagliflozin group and 504 (15·2%) of 3305 patients in the placebo group (hazard ratio 0·71 [95% CI 0·62–0·81]), with no evidence that the relative effect size varied significantly by primary kidney disease (pheterogeneity=0·62). The between-group difference in chronic eGFR slopes (ie, from 2 months to final follow-up) was 1·37 mL/min per 1·73 m2 per year (95% CI 1·16–1·59), representing a 50% (42–58) reduction in the rate of chronic eGFR decline. This relative effect of empagliflozin on chronic eGFR slope was similar in analyses by different primary kidney diseases, including in explorations by type of glomerular disease and diabetes (p values for heterogeneity all >0·1). Interpretation: In a broad range of patients with chronic kidney disease at risk of progression, including a wide range of non-diabetic causes of chronic kidney disease, empagliflozin reduced risk of kidney disease progression. Relative effect sizes were broadly similar irrespective of the cause of primary kidney disease, suggesting that SGLT2 inhibitors should be part of a standard of care to minimise risk of kidney failure in chronic kidney disease. Funding: Boehringer Ingelheim, Eli Lilly, and UK Medical Research Council
Good governance in the hand of the judiciary: Lessons from the European example
This note is based on the author’s guest presentation delivered at the Konrad-Adenauer Foundation/North-West University (Faculty of Law) Colloquium on 21 August 2009. Justice von Danwitz was invited to set the scene for further academic discourse on the broad topic of Good Governance and Sustainable Development. This contribution hence draws on the author’s personal views and experience in the European context, and it is shown that the quest for good governance is universal and not specific to our times and that in fact, “(t)he true administration of justice is the firmest pillar of good government”. The contribution considers what Europe has been able to realize in this field over the past 10 years by means of a description of the legal concepts and practical consequences of the quest for good governance in the European Union and some comments on the role of the judiciary in this process. The contribution serves to show that good government is a notion of which the meaningtranscends geographical and jurisdictional borders and that it is possible for different countries and regions to exchange lessons and learning experiences in relation to good government in operation as well as the role of good government towards the achievement of sustainable development.Keywords: good government, good governance, role of judiciary in goodgovernance; European Union perspective