42 research outputs found

    Earth Virtualization Engines -- A Technical Perspective

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    Participants of the Berlin Summit on Earth Virtualization Engines (EVEs) discussed ideas and concepts to improve our ability to cope with climate change. EVEs aim to provide interactive and accessible climate simulations and data for a wide range of users. They combine high-resolution physics-based models with machine learning techniques to improve the fidelity, efficiency, and interpretability of climate projections. At their core, EVEs offer a federated data layer that enables simple and fast access to exabyte-sized climate data through simple interfaces. In this article, we summarize the technical challenges and opportunities for developing EVEs, and argue that they are essential for addressing the consequences of climate change

    Pharmacokinetics of meropenem in septic patients on sustained low-efficiency dialysis: a population pharmacokinetic study

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    The aim of the study was to describe the population pharmacokinetics (PK) of meropenem in critically ill patients receiving sustained low-efficiency dialysis (SLED).Prospective population PK study on 19 septic patients treated with meropenem and receiving SLED for acute kidney injury. Serial blood samples for determination of meropenem concentrations were taken before, during and after SLED in up to three sessions per patient. Nonparametric population PK analysis with Monte Carlo simulations were used. Pharmacodynamic (PD) targets of 40% and 100% time above the minimal inhibitory concentration (f T > MIC) were used for probability of target attainment (PTA) and fractional target attainment (FTA) against Pseudomonas aeruginosa.A two-compartment linear population PK model was most appropriate with residual diuresis supported as significant covariate affecting meropenem clearance. In patients without residual diuresis the PTA for both targets (40% and 100% f T > MIC) and susceptible P. aeruginosa (MIC ≤ 2\ua0mg/L) was > 95% for a dose of 0.5\ua0g 8-hourly. In patients with a residual diuresis of 300\ua0mL/d 1\ua0g 12-hourly and 2\ua0g 8-hourly would be required to achieve a PTA of > 95% and 93% for targets of 40% f T > MIC and 100% f T > MIC, respectively. A dose of 2\ua0g 8-hourly would be able to achieve a FTA of 97% for 100% f T > MIC in patients with residual diuresis.We found a relevant PK variability for meropenem in patients on SLED, which was significantly influenced by the degree of residual diuresis. As a result dosing recommendations for meropenem in patients on SLED to achieve adequate PD targets greatly vary. Therapeutic drug monitoring may help to further optimise individual dosing.Clincialtrials.gov, NCT02287493

    Population pharmacokinetics and dosing simulations of ceftazidime in critically ill patients receiving sustained low-efficiency dialysis

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    Objectives: To describe the population PKs of ceftazidime in critically ill patients receiving sustained low-efficiency dialysis (SLED)
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