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Background: Sodium oxybate (SMO) has been shown to be effective in the maintenance of abstinence (MoA) in alcohol-dependent patients in a series of small randomized controlled trials (RCTs). These results needed to be confirmed by a large trial investigating the treatment effect and its sustainability after medication discontinuation. Aims: To confirm the SMO effect on (sustained) MoA in detoxified alcohol-dependent patients. Methods: Large double-blind, randomized, placebo-controlled trial in detoxified adult alcohol-dependent outpatients (80% men) from 11 sites in four European countries. Patients were randomized to 6 months SMO (3.3–3.9 g/day) or placebo followed by a 6-month medication-free period. Primary outcome was the cumulative abstinence duration (CAD) during the 6-month treatment period defined as the number of days with no alcohol use. Secondary outcomes included CAD during the 12-month study period. Results: Of the 314 alcohol-dependent patients randomized, 154 received SMO and 160 received placebo. Based on the pre-specified fixed-effect two-way analysis of variance including the treatment-by-site interaction, SMO showed efficacy in CAD during the 6-month treatment period: mean difference +43.1 days, 95% confidence interval (17.6–68.5; p = 0.001). Since significant heterogeneity of effect across sites and unequal sample sizes among sites ( n = 3–66) were identified, a site-level random meta-analysis was performed with results supporting the pre-specified analysis: mean difference +32.4 days, p = 0.014. The SMO effect was sustained during the medication-free follow-up period. SMO was well-tolerated. Conclusions: Results of this large RCT in alcohol-dependent patients demonstrated a significant and clinically relevant sustained effect of SMO on CAD. Trial registration: ClinicalTrials.gov Identifier: NCT04648423

Abstract An assessment of the human impact on the global water cycle requires estimating the volume of water withdrawn for irrigated agriculture. A key parameter in this calculation is the irrigation efficiency, which corrects for the fraction of water lost between irrigation withdrawals and the crop due to management, distribution or conveyance losses. Here we show that the irrigation efficiency used in global irrigation models is flawed for it overlooks key ambiguities in partial efficiencies, irrigation technologies, the definition of ‘large-scale’ irrigated areas or managerial factors. Once accounted for, these uncertainties can make irrigation withdrawal estimates fluctuate by more than one order of magnitude at the country level. Such variability is larger and leads to more extreme values than that caused by the uncertainties related with climate change. Our results highlight the need to embrace deep uncertainties in irrigation efficiency to prevent the design of shortsighted policies at the river basin-water-agricultural interface.

Silver nanoparticles (AgNP) are currently defined as emerging pollutants in surface water ecosystems. Whether the toxic effects of AgNP towards freshwater organisms are fully explainable by the release of ionic silver (Ag(+)) has not been conclusively elucidated. Long-term effects to benthic microbial communities (periphyton) that provide essential functions in stream ecosystems are unknown. The effects of exposure of periphyton to 2 and 20 μg/L Ag(+) (AgNO3) and AgNP (polyvinylpyrrolidone stabilised) were investigated in artificial indoor streams. The extracellular polymeric substances (EPS) and 3D biofilm structure, biomass, algae species, Ag concentrations in the water phase and bioassociated Ag were analysed. A strong decrease in total Ag was observed within 4 days. Bioassociated Ag was proportional to dissolved Ag indicating a rate limitation by diffusion across the diffusive boundary layer. Two micrograms per liter of AgNO3 or AgNP did not induce significant effects despite detectable bioassociation of Ag. The 20-μg/L AgNO3 affected green algae and diatom communities, biomass and the ratio of polysaccharides to proteins in EPS. The 20-μg/L AgNO3 and AgNP decreased biofilm volume to about 50 %, while the decrease of biomass was lower in 20 μg/L AgNP samples than the 20-μg/L AgNO3 indicating a compaction of the NP-exposed biofilms. Roughness coefficients were lower in 20 μg/L AgNP-treated samples. The more traditional endpoints (biomass and diversity) indicated silver ion concentration-dependent effects, while the newly introduced parameters (3D structure and EPS) indicated both silver ion concentration-dependent effects and effects related to the silver species applied.

Global-scale hydrological models are routinely used to assess water scarcity, flood hazards and droughts worldwide. Recent efforts to incorporate anthropogenic activities in these models have enabled more realistic comparisons with observations. Here we evaluate simulations from an ensemble of six models participating in the second phase of the Inter-Sectoral Impact Model Inter-comparison Project (ISIMIP2a). We simulate monthly runoff in 40 catchments, spatially distributed across eight global hydrobelts. The performance of each model and the ensemble mean is examined with respect to their ability to replicate observed mean and extreme runoff under human-influenced conditions. Application of a novel integrated evaluation metric to quantify the models' ability to simulate timeseries of monthly runoff suggests that the models generally perform better in the wetter equatorial and northern hydrobelts than in drier southern hydrobelts. When model outputs are temporally aggregated to assess mean annual and extreme runoff, the models perform better. Nevertheless, we find a general trend in the majority of models towards the overestimation of mean annual runoff and all indicators of upper and lower extreme runoff. The models struggle to capture the timing of the seasonal cycle, particularly in northern hydrobelts, while in southern hydrobelts the models struggle to reproduce the magnitude of the seasonal cycle. It is noteworthy that over all hydrological indicators, the ensemble mean fails to perform better than any individual model—a finding that challenges the commonly held perception that model ensemble estimates deliver superior performance over individual models. The study highlights the need for continued model development and improvement. It also suggests that caution should be taken when summarising the simulations from a model ensemble based upon its mean output. Environmental Research Letters, 13 (6) ISSN:1748-9326 ISSN:1748-9318

The UN Sustainable Development Goals (SDGs) and the Paris Agreement have ushered in a new era of policymaking to deliver on the formulated goals. Energy policies are key to ensuring universal access to affordable, reliable, sustainable, and modern energy (SDG7). Yet they can also have considerable impact on other goals. To successfully achieve multiple goals concurrently, policies need to balance different objectives and manage their interactions. Refining previously contemplated design principles, we identify three key principles - complementary, transparency and adaptability - as highly pertinent for multiple-objective energy policies based on a synthesis of seventeen coordinated policy case studies. First, policies should entail complementary measures and design provisions that specifically target non-energy objectives (complementarity). Second, policy impacts should be tracked comprehensively in both energy and non-energy domains to uncover diminishing returns and facilitate policy learning (transparency). Third, policies should be capable of adapting to changing objectives over time (adaptability). These principles are rarely considered in current policies, implying the need to mainstream them into the next generation of policymaking by pointing to best practices and new tools.

Abstract To improve food security a conceptual integration beyond the scope of production in the agricultural sector due to examination of critical supply chain system compartments and levels of services (“integrated food production and supply systems”) is proposed. For creating systematic results, a platform integrating various perspectives of experts has been established following the principle of triple helix stakeholdership (business practice, public management/policy and also science). During a series of workshops, the main actors, success factors, challenges and communication strategies have been identified for shaping sustainable food supply chains under use of systems thinking and the application of Participatory Systems mapping (PSM). In this line, the paper presents how “system maps” based on the method of PSM are used to gain insights into sustainable logistics services facilitating sustainable consumption patterns, enabling participatory considerations and the productive exchange of knowledge.