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The CO2 source and sink distribution across Europe can be estimated in principle through inverse methods by combining CO2 observations and atmospheric transport models. Uncertainties of such estimates are mainly due to insufficient spatiotemporal coverage of CO2 observations and biases of the models. In order to assess the biases related to the use of different models the CO2 concentration field over Europe has been simulated with five different Eulerian atmospheric transport models as part of the EU-funded AEROCARB project, which has the main goal to estimate the carbon balance of Europe. In contrast to previous comparisons, here both global coarse-resolution and regional higher-resolution models are included. Continuous CO2 observations from continental, coastal and mountain sites as well as flasks sampled on aircrafts are used to evaluate the models' ability to capture the spatiotemporal variability and distribution of lower troposphere CO2 across Europe. 14CO2 is used in addition to evaluate separately fossil fuel signal predictions. The simulated concentrations show a large range of variation, with up to ~10 ppm higher surface concentrations over Western and Central Europe in the regional models with highest (mesoscale) spatial resolution. The simulation - data comparison reveals that generally high-resolution models are more successful than coarse models in capturing the amplitude and phasing of the observed short-term variability. At high-altitude stations the magnitude of the differences between observations and models and in between models is less pronounced, but the timing of the diurnal cycle is not well captured by the models. The data comparisons show also that the timing of the observed variability on hourly to daily time scales at low-altitude stations is generally well captured by all models. However, the amplitude of the variability tends to be underestimated. While daytime values are quite well predicted, nighttime values are generally underpredicted. This is a reflection of the different mixing regimes during day and night combined with different vertical resolution between models. In line with this finding, the agreement among models is increased when sampling in the afternoon hours only and when sampling the mixed portion of the PBL, which amounts to sampling at a few hundred meters above ground. The main recommendations resulting from the study for constraining land carbon sources and sinks using high-resolution concentration data and state-of-the art transport models through inverse methods are given in the following: 1) Low altitude stations are presently preferable in inverse studies. If high altitude stations are used then the model level that represents the specific sites should be applied, 2) at low altitude sites only the afternoon values of concentrations can be represented sufficiently well by current models and therefore afternoon values are more appropriate for constraining large-scale sources and sinks in combination with transport models, 3) even when using only afternoon values it is clear that data sampled several hundred meters above ground can be represented substantially more robustly in models than surface station records, which emphasize the use of tower data in inverse studies and finally 4) traditional large scale transport models seem not sufficient to resolve fine-scale features associated with fossil fuel emissions, as well as larger-scale features like the concentration distribution above the south-western Europe. It is therefore recommended to use higher resolution models for interpretation of continental data in future studies. [ABSTRACT FROM AUTHOR]

Importance: Nitric oxide precursors, such as the amino acid l-arginine and the biguanide antidiabetic drug metformin, have been associated with metabolism and muscle function in patients with Duchenne muscular dystrophy (DMD). The treatment of DMD remains an unmet medical need., Objective: To evaluate the benefits and harms of a combination of l-citrulline and metformin treatment among patients with DMD., Design, Setting, and Participants: A single-center randomized double-blind placebo-controlled parallel-group clinical trial was conducted between December 12, 2013, and March 30, 2016, at the University Children's Hospital Basel in Switzerland. A total of 47 ambulant male patients aged 6.5 to 10 years with genetically confirmed DMD were recruited locally and from the patient registries of Switzerland, Germany, Austria, and France. Data were analyzed from April 6, 2016, to September 5, 2019., Interventions: Patients in the treatment group received 2500 mg of l-citrulline and 250 mg of metformin (combination therapy) 3 times a day for 26 weeks compared with patients in the control group, who received placebo., Main Outcomes and Measures: The primary end point was the change in transfer and standing posture, as assessed by the first dimension of the Motor Function Measure, version 32, from baseline to week 26. Secondary end points included assessments of timed function, quantitative muscle force, biomarkers for muscle necrosis, and adverse events. The 2 prespecified subgroups comprised patients who were able to walk 350 m or more in 6 minutes (stable subgroup) and patients who were not able to walk 350 m in 6 minutes (unstable subgroup) at baseline., Results: Among 49 ambulant male children with DMD who were screened for eligibility, 47 patients with a mean (SD) age of 8.2 (1.1) years were randomized to a treatment group receiving combination therapy (n = 23) or a control group receiving placebo (n = 24), and 45 patients completed the study. No significant differences between groups were found in the results of timed function and muscle force tests for overall, proximal and axial, and distal motor function. Among patients receiving combination therapy, the Motor Function Measure first dimension subscore decrease was 5.5% greater than that of patients receiving placebo (95% CI, -1.0% to 12.1%; P = .09). The administration of combination therapy had significantly favorable effects on the first dimension subscore decrease among the 29 patients in the stable subgroup (6.7%; 95% CI, 0.9%-12.6%; P = .03) but not among the 15 patients in the unstable subgroup (3.9%; 95% CI, -13.2% to 20.9%; P = .63). Overall, the treatment was well tolerated with only mild adverse effects., Conclusions and Relevance: Treatment with combination therapy was not associated with an overall reduction in motor function decline among ambulant patients with DMD; however, a reduction in motor function decline was observed among the stable subgroup of patients treated with combination therapy. The statistically nonsignificant difference of distal motor function in favor of combination therapy and the reduced degeneration of muscle tissue appear to support the treatment concept, but the study may have lacked sufficient statistical power. Further research exploring this treatment option with a greater number of patients is warranted., Trial Registration: ClinicalTrials.gov identifier: NCT01995032.