@misc{PalmerGregoryBaggeetal.2020, author = {Palmer, Matthew D. and Gregory, Jonathan and Bagge, Meike and Calvert, Daley and Hagedoorn, Jan Marius and Howard, Tom and Klemann, Volker and Lowe, Jason A. and Roberts, Chris and Slangen, Aimee B. A. and Spada, Giorgio}, title = {Exploring the drivers of global and local sea-level change over the 21st century and beyond}, series = {Zweitver{\"o}ffentlichungen der Universit{\"a}t Potsdam : Mathematisch-Naturwissenschaftliche Reihe}, journal = {Zweitver{\"o}ffentlichungen der Universit{\"a}t Potsdam : Mathematisch-Naturwissenschaftliche Reihe}, number = {9}, issn = {1866-8372}, doi = {10.25932/publishup-54988}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-549881}, pages = {27}, year = {2020}, abstract = {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.}, language = {en} } @article{PalmerGregoryBaggeetal.2020, author = {Palmer, Matthew D. and Gregory, Jonathan and Bagge, Meike and Calvert, Daley and Hagedoorn, Jan Marius and Howard, Tom and Klemann, Volker and Lowe, Jason A. and Roberts, Chris and Slangen, Aimee B. A. and Spada, Giorgio}, title = {Exploring the drivers of global and local sea-level change over the 21st century and beyond}, series = {Earth's future}, volume = {8}, journal = {Earth's future}, number = {9}, publisher = {Wiley-Blackwell}, address = {Hoboken}, issn = {2328-4277}, doi = {10.1029/2019EF001413}, pages = {1 -- 25}, year = {2020}, abstract = {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.}, language = {en} } @article{MinichmayrRobertsFreyetal.2018, author = {Minichmayr, Iris K. and Roberts, Jason A. and Frey, Otto R. and Roehr, Anka C. and Kloft, Charlotte and Brinkmann, Alexander}, title = {Development of a dosing nomogram for continuous-infusion meropenem in critically ill patients based on a validated population pharmacokinetic model}, series = {Journal of Antimicrobial Chemotherapy}, volume = {73}, journal = {Journal of Antimicrobial Chemotherapy}, number = {5}, publisher = {Oxford Univ. Press}, address = {Oxford}, issn = {0305-7453}, doi = {10.1093/jac/dkx526}, pages = {1330 -- 1339}, year = {2018}, abstract = {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.}, language = {en} }