TY - GEN A1 - Palmer, Matthew D. A1 - Gregory, Jonathan A1 - Bagge, Meike A1 - Calvert, Daley A1 - Hagedoorn, Jan Marius A1 - Howard, Tom A1 - Klemann, Volker A1 - Lowe, Jason A. A1 - Roberts, Chris A1 - Slangen, Aimee B. A. A1 - Spada, Giorgio T1 - Exploring the drivers of global and local sea‐level change over the 21st century and beyond T2 - Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe N2 - We present a new set of global and local sea‐level projections at example tide gauge locations under the RCP2.6, RCP4.5, and RCP8.5 emissions scenarios. Compared to the CMIP5‐based sea‐level projections presented in IPCC AR5, we introduce a number of methodological innovations, including (i) more comprehensive treatment of uncertainties, (ii) direct traceability between global and local projections, and (iii) exploratory extended projections to 2300 based on emulation of individual CMIP5 models. Combining the projections with observed tide gauge records, we explore the contribution to total variance that arises from sea‐level variability, different emissions scenarios, and model uncertainty. For the period out to 2300 we further breakdown the model uncertainty by sea‐level component and consider the dependence on geographic location, time horizon, and emissions scenario. Our analysis highlights the importance of local variability for sea‐level change in the coming decades and the potential value of annual‐to‐decadal predictions of local sea‐level change. Projections to 2300 show a substantial degree of committed sea‐level rise under all emissions scenarios considered and highlight the reduced future risk associated with RCP2.6 and RCP4.5 compared to RCP8.5. Tide gauge locations can show large ( > 50%) departures from the global average, in some cases even reversing the sign of the change. While uncertainty in projections of the future Antarctic ice dynamic response tends to dominate post‐2100, we see substantial differences in the breakdown of model variance as a function of location, time scale, and emissions scenario. T3 - Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe - 1353 KW - climate change KW - CMIP5 models KW - RCP scenarios KW - sea-level projections KW - tide gauge observations Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-549881 SN - 1866-8372 IS - 9 ER - TY - JOUR A1 - Palmer, Matthew D. A1 - Gregory, Jonathan A1 - Bagge, Meike A1 - Calvert, Daley A1 - Hagedoorn, Jan Marius A1 - Howard, Tom A1 - Klemann, Volker A1 - Lowe, Jason A. A1 - Roberts, Chris A1 - Slangen, Aimee B. A. A1 - Spada, Giorgio T1 - Exploring the drivers of global and local sea‐level change over the 21st century and beyond JF - Earth's future N2 - We present a new set of global and local sea‐level projections at example tide gauge locations under the RCP2.6, RCP4.5, and RCP8.5 emissions scenarios. Compared to the CMIP5‐based sea‐level projections presented in IPCC AR5, we introduce a number of methodological innovations, including (i) more comprehensive treatment of uncertainties, (ii) direct traceability between global and local projections, and (iii) exploratory extended projections to 2300 based on emulation of individual CMIP5 models. Combining the projections with observed tide gauge records, we explore the contribution to total variance that arises from sea‐level variability, different emissions scenarios, and model uncertainty. For the period out to 2300 we further breakdown the model uncertainty by sea‐level component and consider the dependence on geographic location, time horizon, and emissions scenario. Our analysis highlights the importance of local variability for sea‐level change in the coming decades and the potential value of annual‐to‐decadal predictions of local sea‐level change. Projections to 2300 show a substantial degree of committed sea‐level rise under all emissions scenarios considered and highlight the reduced future risk associated with RCP2.6 and RCP4.5 compared to RCP8.5. Tide gauge locations can show large ( > 50%) departures from the global average, in some cases even reversing the sign of the change. While uncertainty in projections of the future Antarctic ice dynamic response tends to dominate post‐2100, we see substantial differences in the breakdown of model variance as a function of location, time scale, and emissions scenario. KW - climate change KW - CMIP5 models KW - RCP scenarios KW - sea-level projections KW - tide gauge observations Y1 - 2020 U6 - https://doi.org/10.1029/2019EF001413 SN - 2328-4277 VL - 8 IS - 9 SP - 1 EP - 25 PB - Wiley-Blackwell CY - Hoboken ER - TY - JOUR A1 - Minichmayr, Iris K. A1 - Roberts, Jason A. A1 - Frey, Otto R. A1 - Roehr, Anka C. A1 - Kloft, Charlotte A1 - Brinkmann, Alexander T1 - Development of a dosing nomogram for continuous-infusion meropenem in critically ill patients based on a validated population pharmacokinetic model JF - Journal of Antimicrobial Chemotherapy N2 - Background: Optimal antibiotic exposure is a vital but challenging prerequisite for achieving clinical success in ICU patients. Objectives: To develop and externally validate a population pharmacokinetic model for continuous-infusion meropenem in critically ill patients and to establish a nomogram based on a routinely available marker of renal function. Methods: A population pharmacokinetic model was developed in NONMEM (R) 7.3 based on steady-state meropenem concentrations (C-ss) collected during therapeutic drug monitoring. Different serum creatinine-based markers of renal function were compared for their influence on meropenem clearance (the Cockcroft-Gault creatinine clearance CLCRcG, the CLCR bedside estimate according to Jelliffe, the Chronic Kidney Disease Epidemiology Collaboration equation and the four-variable Modification of Diet in Renal Disease equation). After validation of the pharmacokinetic model with independent data, a dosing nomogram was developed, relating renal function to the daily doses required to achieve selected target concentrations (4/8/16 mg/L) in 90% of the patients. Probability of target attainment was determined for efficacy (C-ss >= 8 mg/L) and potentially increased likelihood of adverse drug reactions (C-ss >32 mg/L). Results: In total, 433 plasma concentrations (3.20-48.0 mg/L) from 195 patients (median/P-0.05 - P-0.95 at baseline: weight 77.0/55.0-114 kg, CLCRCG 63.0/19.6-168 mL/min) were used for model building. We found that CLCRCG best described meropenem clearance (CL = 7.71 L/h, CLCRCG = 80 mL/min). The developed model was successfully validated with external data (n = 171, 73 patients). According to the nomogram, daily doses of 910/1480/2050/2800/ 3940 mg were required to reach a target C-ss = 8 mg/L in 90% of patients with CLCRCG = 20/50/80/120/180 mL/min, respectively. A low probability of adverse drug reactions (<0.5%) was associated with these doses. Conclusions: A dosing nomogram was developed for continuous-infusion meropenem based on renal function in a critically ill population. Y1 - 2018 U6 - https://doi.org/10.1093/jac/dkx526 SN - 0305-7453 SN - 1460-2091 VL - 73 IS - 5 SP - 1330 EP - 1339 PB - Oxford Univ. Press CY - Oxford ER -