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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Abstract An assessment of the human impact on the global water cycle requires estimating the volume of water withdrawn for irrigated agriculture.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.

ObjectivesHeavy alcohol use can cause somatic and mental diseases, affects patients’ social life and is associated with social isolation, unemployment and reduced quality of life. Therefore, societal costs of alcohol dependence are expected to be high. The aim of this study was to estimate excess costs of patients with alcohol dependence diagnosed using theDiagnostic and Statistical Manual of Mental Disorders, 4th Edition criteria compared with individuals without alcohol dependence in Germany.DesignIn a secondary analysis, baseline data of patients with alcohol dependence enrolled in a randomised controlled trial (German Clinical Trials Register DRS00005035) were compared with data collected via a telephone survey from individuals without alcohol dependence and that had been matched by entropy balancing. Health service use was evaluated retrospectively for a 6-month period.SettingsFour German psychiatric university clinics (patients with alcohol dependence) and the German general adult population (individuals without alcohol dependence).Participantsn=236 adult patients with alcohol dependence and n=4687 adult individuals without alcohol dependence.Primary and secondary outcome measuresThe excess costs of health service use, absenteeism and unemployment of patients with alcohol dependence were calculated and compared with individuals without alcohol dependence. In subgroup analyses, the associations between excess cost and gender, comorbidities and the duration of disease were investigated.ResultsTotal 6-month excess costs of €11 839 (95% CI €11 529 to €12 147) were caused by direct excess costs of €4349 (95% CI €4129 to €4566) and indirect costs of €7490 (95% CI €5124 to €9856). In particular, costs of inpatient treatment, formal long-term care, absenteeism and unemployment were high.ConclusionsAlcohol dependence causes substantial direct and indirect excess costs. Cost-effective interventions to prevent and treat alcohol dependence are urgently needed.Trial registration numberDRKS00005035.

Abstract A central challenge of today's ecological research is predicting how ecosystems will develop under future global change. Accurate predictions are complicated by (a) simultaneous effects of different drivers, such as climate change, nitrogen deposition and management changes; and (b) legacy effects from previous land use. We tested whether herb layer biodiversity (i.e. richness, Shannon diversity and evenness) and functional (i.e. herb cover, specific leaf area [SLA] and plant height) responses to environmental change drivers depended on land‐use history. We used resurvey data from 192 plots across nineteen European temperate forest regions, with large spatial variability in environmental change factors. We tested for interactions between land‐use history, distinguishing ancient and recent (i.e. post‐agricultural) forests and four drivers: temperature, nitrogen deposition, and aridity at the regional scale and light dynamics at the plot‐scale. Land‐use history significantly modulated global change effects on the functional signature of the herb layer (i.e. cover, SLA and plant height). Light availability was the main environmental driver of change interacting with land‐use history. We found greater herb cover and plant height decreases and SLA increases with decreasing light availability in ancient than in recent forests. Furthermore, we found greater decreases in herb cover with increased nitrogen deposition in ancient forests, whereas warming had the strongest decreasing effect on the herb cover in recent forests. Interactive effects between land‐use history and global change on biodiversity were not found, but species evenness increased more in ancient than in recent forests. Synthesis. Our results demonstrate that land‐use history should not be overlooked when predicting forest herb layer responses to global change. Moreover, we found that herb layer composition in semi‐natural deciduous forests is mainly controlled by local canopy characteristics, regulating light levels at the forest floor, and much less by environmental changes at the regional scale (here: warming, nitrogen deposition and aridity). The observed disconnect between biodiversity and functional herb layer responses to environmental changes demonstrates the importance of assessing both types of responses to increase our understanding of the possible impact of global change on the herb layer.

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.

Land use is central to addressing sustainability issues, including biodiversity conservation, climate change, food security, poverty alleviation, and sustainable energy. In this paper, we synthesize knowledge accumulated in land system science, the integrated study of terrestrial social-ecological systems, into 10 hard truths that have strong, general, empirical support. These facts help to explain the challenges of achieving sustainability in land use and thus also point toward solutions. The 10 facts are as follows: 1) Meanings and values of land are socially constructed and contested; 2) land systems exhibit complex behaviors with abrupt, hard-to-predict changes; 3) irreversible changes and path dependence are common features of land systems; 4) some land uses have a small footprint but very large impacts; 5) drivers and impacts of land-use change are globally interconnected and spill over to distant locations; 6) humanity lives on a used planet where all land provides benefits to societies; 7) land-use change usually entails trade-offs between different benefits—"win–wins" are thus rare; 8) land tenure and land-use claims are often unclear, overlapping, and contested; 9) the benefits and burdens from land are unequally distributed; and 10) land users have multiple, sometimes conflicting, ideas of what social and environmental justice entails. The facts have implications for governance, but do not provide fixed answers. Instead they constitute a set of core principles which can guide scientists, policy makers, and practitioners toward meeting sustainability challenges in land use.