Erratum to: 36th International Symposium on Intensive Care and Emergency Medicine

[This corrects the article DOI: 10.1186/s13054-016-1208-6.]

4D objects-by-change: Spatiotemporal segmentation of geomorphic surface change from LiDAR time series

Time series of topographic data are becoming increasingly widespread for monitoring geomorphic activity. Dense 3D time series are now obtained by near-continuous terrestrial laser scanning (TLS) installations, which acquire data at high frequency (e.g. hourly) and over long periods. Such datasets contain valuable information on topographic evolution over varying spatial and temporal scales. Current analyses however are mostly conducted based on pairwise surface or object-based change, which typically require the selection of thresholds and intervals to identify the processes involved and fail to account for the full history of change. Detected change may therefore be difficult to attribute to one or more underlying geomorphic processes causing the surface alteration. We present an automatic method for 4D change analysis that includes the temporal domain by using the history of surface change to extract the period and spatial extent of changes. A 3D space-time array of surface change values is derived from an hourly TLS time series acquired at a sandy beach over five months (2967 point clouds). Change point detection is performed in the time series at individual locations and used to identify change processes, such as the appearance and disappearance of an accumulation form. These provide the seed to spatially segment ‘4D objects-by-change’ using a metric of time series similarity in a region growing approach. Results are compared to pairwise surface change for three selected cases of anthropogenic and natural processes on the beach. The obtained information reflects the evolution of a change process and its spatial extent over the change period, thereby improving upon the results of pairwise analysis. The method allows the detection and spatiotemporal delineation of even subtle changes induced by sand transport on the surface. 4D objects-by-change can therefore provide new insights on spatiotemporal characteristics of geomorphic activity, particularly in settings of continuous surfaces with dynamic morphologies.Accepted Author ManuscriptOptical and Laser Remote SensingCoastal 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