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An emerging approach for large-scale hydrogen production using renewable energy is to integrate multiple alkaline water electrolysis (AWE) stacks into a single balance of plant (BoP) system, sharing components such as gas-lye separation and lye circulation. This configuration, termed the $N$-in-1 AWE system, packs $N$ stacks into a modular system, reducing land requirements, the complexity of plant topology, and overall capital costs. However, the coupling of these stacks through the shared BoP introduces challenges in dynamic operation under varying energy inputs, making their performance unclear compared to traditional 1-in-1 systems. To address this, we develop a state-space model of the $N$-in-1 AWE system, capturing the dynamic behaviors of lye circulation, temperature, and HTO impurity, and their impact on energy conversion efficiency. We then propose a nonlinear model predictive controller (NMPC) to coordinately optimize inter-stack electrolytic current distribution, lye flow, and cooling, enabling the system to dynamically track varying load commands while maximizing efficiency, stabilizing temperature, and limiting HTO impurity accumulation. Simulation studies on a 4,000 Nm$^3$/h-rated 4-in-1 system verify the proposed controller under dynamic operation. Comparison with 4 independent 1-in-1 systems reveals that, with proper control, the $N$-in-1 configuration offers comparable flexibility in accommodating real-world wind power inputs. The average differences in the root-mean-square errors (RMSEs) for load-tracking and stack temperature stabilization, and specific energy consumption are below 0.014 MW, 2.356 K, and 0.003 kWh/Nm$^3$.

When directly coupled with fluctuating energy sources such as wind and photovoltage power, the alkaline electrolysis (AEL) in a power-to-hydrogen (P2H) system is required to operate flexibly by dynamically adjusting its hydrogen production rate. The flex-ibility characteristics, e.g., loading range and ramping rate, of an AEL system are significantly influenced by some parameters re-lated to the dynamic processes of the AEL system. These parame-ters are usually difficult to measure directly and may even change with time. To accurately evaluate the flexibility of an AEL system in online operation, this paper presents a Bayesian Inference-based Markov Chain Monte Carlo (MCMC) method to estimate these parameters. Meanwhile, posterior joint probability distribu-tions of the estimated parameters are obtained as a byproduct, which provides valuable physical insight into the AEL systems. Experiments on a 25 kW electrolyzer validate the proposed pa-rameter estimation method., Comment: Accepted by 2022 IEEE 5th International Electrical and Energy Conference

Aim The pharmacokinetic (PK) properties of cyclosporine (CsA) in renal transplant recipients are patient- and time-dependent. Knowledge of this time-related variability is necessary to maintain or achieve CsA target exposure. Here, we aimed to identify factors explaining variabilities in CsA PK properties and characterise time-dependent clearance (CL/F) by performing a comprehensive analysis of CsA PK factors using population PK (popPK) modelling of long-term follow-up data from our institution. Methods In total, 3,674 whole-blood CsA concentrations from 183 patients who underwent initial renal transplantation were analysed using nonlinear mixed-effects modelling. The effects of potential covariates were selected according to a previous report and well-accepted theoretical mechanisms. Model-informed individualised therapeutic regimens were also conducted. Results A two-compartment model adequately described the data and the estimated mean CsA CL/F was 32.6 L h-1 (5%). Allometrically scaled body size, haematocrit (HCT) level, CGC haplotype carrier status, and postoperative time may contribute to CsA PK variability. The CsA bioavailability in patients receiving a prednisolone dose (PD) of 80 mg was 20.6% lower than that in patients receiving 20 mg. A significant decrease (52.6%) in CL/F was observed as the HCT increased from 10.5% to 60.5%. The CL/F of the non-CGC haplotype carrier was 14.4% lower than that of the CGC haplotype carrier at 3 months post operation. CsA dose adjustments should be considered in different postoperative periods. Conclusions By monitoring body size, HCT, PD, and CGC haplotype, changes in CsA CL/F over time could be predicted. Such information could be used to optimise CsA therapy.

AIMS A population pharmacokinetic (PK) analysis was performed to: (1) characterise the PK of unbound and total mycophenolic acid (MPA) and its 7-O-mycophenolic acid glucuronide (MPAG) metabolite, and (2) identify the clinically significant covariates that cause variability in the dose-exposure relationship to facilitate dose optimisation. METHODS A total of 740 unbound MPA (uMPA), 741 total MPA (tMPA) and 734 total MPAG (tMPAG) concentration-time data from 58 Chinese kidney transplant patients were analysed using a nonlinear mixed-effect model. The influence of covariates was tested using a stepwise procedure. RESULTS The PK of unbound MPA and MPAG were characterised by a two- and one-compartment model with first-order elimination, respectively. Apparent clearance of uMPA (CLuMPA/F) was estimated to be 852 L/h with a relative standard error (RSE) of 7.1%. The tMPA and uMPA were connected using a linear protein binding model, in which the protein binding rate constant (kB) increased non-linearly with the serum albumin (ALB) concentration. The estimated kB was 53.4 /h (RSE, 2.3%) for patients with ALB of 40 g/L. In addition, model-based simulation showed that changes in ALB substantially affected tMPA but not uMPA exposure. CONCLUSIONS The established model adequately described the population PK characteristics of the uMPA, tMPA, and MPAG. The estimated CLuMPA/F and unbound fraction of MPA (FUMPA) in Chinese kidney transplant recipients were comparable to those published previously in Caucasians. We recommend monitoring uMPA instead of tMPA to optimise mycophenolate mofetil (MMF) dosing for patients with lower ALB levels., Comment: 39 pages, 3 tables, 5 figures, 1 supplementary table and 1 supplementary figure

Background:Diverse tacrolimus population pharmacokinetic models in adult liver transplant recipients have been established to describe the PK characteristics of tacrolimus in the last two decades. However, their extrapolated predictive performance remains unclear.Therefore,in this study,we aimed to evaluate their external predictability and identify their potential influencing factors. Methods:The external predictability of each selected popPK model was evaluated using an independent dataset of 84 patients with 572 trough concentrations prospectively collected from Huashan Hospital. Prediction and simulation based diagnostics and Bayesian forecasting were conducted to evaluate model predictability. Furthermore, the effect of model structure on the predictive performance was investigated.Results:Sixteen published popPK models were assessed. In prediction-based diagnostics,the prediction error within 30% was below 50% in all the published models. The simulation based normalised prediction distribution error test and visual predictive check indicated large discrepancies between the observations and simulations in most of the models. Bayesian forecasting showed improvement in model predictability with two to three prior observations. Additionally, the predictive performance of the nonlinear Michaelis Menten model was superior to that of linear compartment models,indicating the underlying nonlinear kinetics of tacrolimus in liver transplant recipients.Conclusions:The published models performed inadequately in prediction and simulation based diagnostics. Bayesian forecasting may improve the predictive performance of the models. Furthermore, nonlinear kinetics of tacrolimus may be mainly caused by the properties of the drug itself, and incorporating nonlinear kinetics may be considered to improve model predictability.