Generalizing rapid flood predictions to unseen urban catchments with conditional generative adversarial networks

Two-dimensional hydrodynamic models are computationally expensive. This drawback can limit their application to solving problems requiring real-time predictions or several simulation runs. Although the literature presented improvements in using Deep Learning as an alternative to hydrodynamic models, Artificial Neural Networks applications for flood prediction cannot satisfactorily predict floods for areas outside the training datasets with different boundary conditions. In this paper, we used a conditional generative adversarial network (cGAN) aiming to generalize flood predictions in catchments not included in the training process. The proposed method, called cGAN-Flood, uses two cGAN models to solve a rain-on-grid problem by first identifying wet cells and then estimating the water depths. The cGANs were trained using HEC-RAS outputs as ground truth. cGAN-Flood distributes a target flood volume (vt) in a given catchment, which can be calculated via water balance from hydrological simulations. Our approach was trained on ten and tested on five urban catchments with distinct characteristics. The cGAN-Flood was compared to HEC-RAS for different rainfall magnitudes and surface roughness. We also compared our approach to the Weighted Cellular Automata 2D (WCA2D), a rapid flood model (RFM) used for rain-on-grid simulations. Our method successfully predicted water depths in the testing areas, showing that cGAN-Flood could generalize to different locations. However, cGAN-Flood tended to underestimate depths in channels in some areas for events with a small peak of precipitation intensity. cGAN-Flood was 50 and 250 times faster than WCA2D and HEC-RAS, respectively. Due to its computational efficiency and accuracy, we suggest that cGAN-Flood can be applied when fast simulations are necessary, and it can be a viable modeling solution for flood forecasts in large-scale watersheds.Green Open Access added to TU Delft Institutional Repository 'You share, we take care!' - Taverne project https://www.openaccess.nl/en/you-share-we-take-care Otherwise as indicated in the copyright section: the publisher is the copyright holder of this work and the author uses the Dutch legislation to make this work public.Sanitary Engineerin

Sparsentan in patients with IgA nephropathy: a prespecified interim analysis from a randomised, double-blind, active-controlled clinical trial

Background: Sparsentan is a novel, non-immunosuppressive, single-molecule, dual endothelin and angiotensin receptor antagonist being examined in an ongoing phase 3 trial in adults with IgA nephropathy. We report the prespecified interim analysis of the primary proteinuria efficacy endpoint, and safety. Methods: PROTECT is an international, randomised, double-blind, active-controlled study, being conducted in 134 clinical practice sites in 18 countries. The study examines sparsentan versus irbesartan in adults (aged ≥18 years) with biopsy-proven IgA nephropathy and proteinuria of 1·0 g/day or higher despite maximised renin-angiotensin system inhibitor treatment for at least 12 weeks. Participants were randomly assigned in a 1:1 ratio to receive sparsentan 400 mg once daily or irbesartan 300 mg once daily, stratified by estimated glomerular filtration rate at screening (30 to 1·75 g/day). The primary efficacy endpoint was change from baseline to week 36 in urine protein-creatinine ratio based on a 24-h urine sample, assessed using mixed model repeated measures. Treatment-emergent adverse events (TEAEs) were safety endpoints. All endpoints were examined in all participants who received at least one dose of randomised treatment. The study is ongoing and is registered with ClinicalTrials.gov, NCT03762850. Findings: Between Dec 20, 2018, and May 26, 2021, 404 participants were randomly assigned to sparsentan (n=202) or irbesartan (n=202) and received treatment. At week 36, the geometric least squares mean percent change from baseline in urine protein-creatinine ratio was statistically significantly greater in the sparsentan group (-49·8%) than the irbesartan group (-15·1%), resulting in a between-group relative reduction of 41% (least squares mean ratio=0·59; 95% CI 0·51-0·69; p<0·0001). TEAEs with sparsentan were similar to irbesartan. There were no cases of severe oedema, heart failure, hepatotoxicity, or oedema-related discontinuations. Bodyweight changes from baseline were not different between the sparsentan and irbesartan groups. Interpretation: Once-daily treatment with sparsentan produced meaningful reduction in proteinuria compared with irbesartan in adults with IgA nephropathy. Safety of sparsentan was similar to irbesartan. Future analyses after completion of the 2-year double-blind period will show whether these beneficial effects translate into a long-term nephroprotective potential of sparsentan. Funding: Travere Therapeutics