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Preclinical studies in rodents have demonstrated inhibitory effects of glucagon-like peptide-1 (GLP-1) receptor stimulation on alcohol consumption. The effects of GLP-1 receptor stimulation on alcohol intake in primates have not been investigated.We performed placebo-controlled studies on the effects of the GLP-1 receptor agonists exenatide and liraglutide on alcohol consumption in alcohol-preferring male African vervet monkeys. Monkeys selected for voluntary alcohol drinking were observed for at least 10 days of baseline drinking and allocated to drug or vehicle (n = 11-12 per group) balanced with respect to alcohol intake. Monkeys had access to alcohol 4 h/day. In a first study, monkeys were treated with exenatide 0.04 mg/kg or vehicle once weekly for 5 weeks to obtain steady-state plasma levels. In a second study, monkeys were treated daily with liraglutide (increasing dosing, 10 to 50 μg/kg/day) or vehicle over 2 weeks. In both studies, access to alcohol was suspended during drug up-titration. Then, alcohol was again made available 4 h/day and treatment was continued for 2 weeks, during which alcohol intake was recorded. Observation of alcohol intake was continued for a week of drug washout.Liraglutide and to a lesser extent exenatide significantly reduced alcohol consumption without causing any signs of emesis and with no effect on water intake as compared to vehicle.The present study demonstrates for the first time that GLP-1 receptor agonists can reduce voluntary alcohol drinking in non-human primates. The data substantiate the potential usefulness of GLP-1 receptor agonists in the treatment of alcohol use disorder.

The relative biological effectiveness (RBE) varies along the treatment field. However, in clinical practice, a constant RBE of 1.1 is assumed, which can result in undesirable side effects. This study provides an accurate overview of current clinical practice for considering proton RBE in Europe.A survey was devised and sent to all proton therapy centres in Europe that treat patients. The online questionnaire consisted of 39 questions addressing various aspects of RBE consideration in clinical practice, including treatment planning, patient follow-up and future demands.All 25 proton therapy centres responded. All centres prescribed a constant RBE of 1.1, but also applied measures (except for one eye treatment centre) to counteract variable RBE effects such as avoiding beams stopping inside or in front of an organ at risk and putting restrictions on the minimum number and opening angle of incident beams for certain treatment sites. For the future, most centres (16) asked for more retrospective or prospective outcome studies investigating the potential effect of the effect of a variable RBE. To perform such studies, 18 centres asked for LET and RBE calculation and visualisation tools developed by treatment planning system vendors.All European proton centres are aware of RBE variability but comply with current guidelines of prescribing a constant RBE. However, they actively mitigate uncertainty and risk of side effects resulting from increased RBE by applying measures and restrictions during treatment planning. To change RBE-related clinical guidelines in the future more clinical data on RBE are explicitly demanded.

Abstract Offshore cultivation of seaweed provides an innovative feedstock for biobased products supporting blue growth in northern Europe. This paper analyzes two alternative exploitation pathways: energy and protein production. The first pathway is based on anaerobic digestion of seaweed which is converted into biogas, for production of electricity and heat, and digestate, used as fertilizer; the second pathway uses seaweed hydrolysate as a substrate for cultivation of heterotrophic microalgae. As a result the seaweed sugars are consumed while new proteins are produced enhancing the total output. We performed a comparative Life Cycle Assessment of five scenarios identifying the critical features affecting resource efficiency and environmental performance of the systems with the aim of providing decision support for the design of future industrial scale production processes. The results show that all scenarios provide environmental benefits in terms of mitigation of climate change, with biogas production from dried Laminaria digitata being the most favorable scenario, quantified as −18.7*10 2 kg CO 2 eq./ha. This scenario presents also the lowest consumption of total cumulative energy demand, 1.7*10 4 MJ/ha, and even resulting in a net reduction of the fossil energy fraction, −1.9*10 4 MJ/ha compared to a situation without seaweed cultivation. All scenarios provide mitigation of marine eutrophication thanks to bioextraction of nitrogen and phosphorus during seaweed growth. The material consumption for seeded lines has 2–20 times higher impact on human toxicity (cancer) than the reduction achieved by energy and protein substitution. However, minor changes in cultivation design, i.e. use of stones instead of iron as ballast to weight the seeded lines, dramatically reduces human toxicity (cancer). Externalities from the use of digestate as fertilizer affect human toxicity (non-cancer) due to transfer of arsenic from aquatic environment to agricultural soil. However concentration of heavy metals in digestate does not exceed the limit established by Danish regulation. The assessment identifies seaweed productivity as the key parameter to further improve the performance of the production systems which are a promising service provider of environmental restoration and climate change mitigation.

The COVID-19 pandemic affects all of society and hinders day-to-day activities from a straightforward perspective. The pandemic has an influential impact on almost everything and the characteristics of the pandemic remain unclear. This ultimately leads to ineffective strategic planning to manage the pandemic. This study aims to elucidate the typical pandemic characteristics in line with various temporal phases and its associated measures that proved effective in controlling the pandemic. Besides, an insight into diverse country's approaches towards pandemic and their consequences is provided in brief. Understanding the role of technologies in supporting humanity gives new perspectives to effectively manage the pandemic. Such role of technologies is expressed from the viewpoint of seamless connectivity, rapid communication, mobility, technological influence in healthcare, digitalization influence, surveillance and security, Artificial Intelligence (AI), and Internet of Things (IoT). Furthermore, some insightful scenarios are framed where the full-fledged implementation of technologies is assumed, and the reflected pandemic impacts in such scenarios are analyzed. The framed scenarios revolve around the digitalized energy sector, an enhanced supply chain system with effective customer-retailer relationships to support the city during the pandemic scenario, and an advanced tracking system for containing virus spread. The study is further extended to frame revitalization strategies to highlight the expertise where significant attention needs to be provided in the post-pandemic period as well as to nurture sustainable development. Finally, the current pandemic scenario is analyzed in terms of occurred changes and is mapped into SWOT factors. Using Fuzzy Technique for Order of Preference by Similarity to Ideal Solution based Multi-Criteria Decision Analysis, these SWOT factors are analyzed to determine where prioritized efforts are needed to focus so as to traverse towards sustainable cities. The results indicate that the enhanced crisis management ability and situational need to restructure the economic model emerges to be the most-significant SWOT factor that can ultimately support humanity for making the cities sustainable.

OBJECTIVEThis study investigated whether preceding ethanol intake impairs glucose response to low-dose glucagon in individuals with type 1 diabetes.RESEARCH DESIGN AND METHODSThis was a randomized, crossover, placebo-controlled study in 12 insulin pump–treated individuals (median [interquartile range] age, 37 [31–51] years; HbA1c, 57 [51–59] mmol/mol or 7.3% [6.8–7.5]; and BMI, 23.9 [22–25] kg/m2). During two overnight study visits, a 6 p.m. dinner (1 g carbohydrates/kg) was served with diet drink (placebo) or diet drink and ethanol (0.8 g/kg). After 8–9 h, ethanol was estimated to be metabolized, and a subcutaneous (s.c.) insulin bolus was given to induce mild hypoglycemia. When plasma glucose (PG) was ≤3.9 mmol/L, 100 µg glucagon was given s.c., followed by another s.c. 100 µg glucagon 2 h later. Primary end point was incremental peak PG induced by the first glucagon bolus.RESULTSEthanol was undetectable before insulin administration at both visits. The insulin doses (mean ± SEM: 2.5 ± 0.4 vs. 2.7 ± 0.4 IU) to induce hypoglycemia (3.7 ± 0.1 vs. 3.9 ± 0.1 mmol/L) did not differ and caused similar insulin levels (28.3 ± 4.6 vs. 26.1 ± 4.0 mU/L) before glucagon administration on ethanol and placebo visits (all, P > 0.05). The first glucagon bolus tended to cause lower incremental peak PG (2.0 ± 0.5 vs. 2.9 ± 0.3 mmol/L, P = 0.06), lower incremental area under the curve (87 ± 40 vs. 191 ± 37 mmol/L × min, P = 0.08), and lower 2-h PG level (3.6 ± 1.0 vs. 4.8 ± 0.4 mmol/L, P = 0.05) after ethanol compared with placebo. The second glucagon bolus had similar responses between visits, but PG remained 1.8 ± 0.7 mmol/L lower after ethanol compared with placebo.CONCLUSIONSThe ability of low-dose glucagon to treat mild hypoglycemia persisted with preceding ethanol intake, although it tended to be attenuated.

VR FestLab is a virtual reality party simulation application. The tool allows users to make decisions while experiencing a virtual party where they are offered alcohol. This study examines the user experience, game satisfaction, and engagement of 181 adolescent users (aged 15–18) with VR FestLab involving seven schools in Denmark. All user experience factors of the short user experience questionnaire were rated positively or neutral, and 66% of the students liked the VR experience. Neither the user experience score nor a score for game satisfaction and engagement were associated with sex, age, perceived family affluence, school performance, alcohol consumption and attitudes or mental health of students. Overall, positive user experiences and game satisfaction of VR FestLab were found not to differ according to student characteristics. We conclude that virtual simulations offer new ways for developing drinking refusal skills that are attractive and acceptable for adolescent users.

Abstract. The impact of air pollution on human health and the associated external costs in Europe and the United States (U.S.) for the year 2010 is modelled by a multi-model ensemble of regional models in the frame of the third phase of the Air Quality Modelling Evaluation International Initiative (AQMEII3). This is the first study known to use a common health assessment approach across the two continents. The modelled surface concentrations of O3, CO, SO2 and PM2.5 from each model are used as input to the Economic Valuation of Air Pollution (EVA) system to calculate the resulting health impacts and the associated external costs. Along with a base case simulation, additional runs were performed introducing 20 % emission reductions both globally and regionally in Europe, North America and East Asia. Health impacts estimated by different models can vary up to a factor of three in Europe (twelve models) and the United States (three models). In Europe, the multi-model mean number of premature deaths is calculated to be 414 000 while in the U.S., it is estimated to be 160 000, in agreement with previous global and regional studies. In order to estimate the impact of biases coming from each model, two multi-model ensembles were produced, the first attributing an equal weight to each member of the ensemble, and the second where the subset of models that produce the smallest error compared to the surface observations at each time step. The latter results in increase of health impacts by up to 30 % in Europe, thus giving significantly higher mortality estimates compared to available literature. This is mostly due to a 27 % increase in the domain mean PM2.5 levels, along with a slight increase in O3 by ~ 1 %. Over the U.S., the mean PM2.5 and O3 levels decrease by 11 % and 2 %, respectively, when the optimal ensemble mean is used, leading to a decrease in the calculated health impacts by ~ 11 %. These differences encourage the use of optimal-reduced multi-model ensembles over traditional all model-mean ensembles, in particular for policy applications. Finally, the role of domestic versus foreign emission sources on the related health impacts is investigated using the 20 % emission reduction scenarios applied over the source regions as defined in the frame of HTAP2. The differences are calculated based on the models that are common in the basic multi-model ensemble and the perturbation scenarios, resulting in five models in Europe and all three models in the U.S. A 20 % reduction of global anthropogenic emissions avoids 54 000 and 27 500 premature deaths in Europe and the U.S., respectively. A 20 % reduction of North American emissions foreign emissions avoids ~ 1000 premature deaths in Europe and 25 000 premature deaths in the U.S. A 20 % decrease of emissions within the European source region avoids 47 000 premature deaths in Europe. Reducing the East Asian emission by 20 % avoids ~ 2000 premature deaths in the U.S. These results show that the domestic emissions make the largest impacts on premature death, while foreign sources make a minor contributing to adverse impacts of air pollution.

AbstractThe Environmental Effects Assessment Panel of the Montreal Protocol under the United Nations Environment Programme evaluates effects on the environment and human health that arise from changes in the stratospheric ozone layer and concomitant variations in ultraviolet (UV) radiation at the Earth’s surface. The current update is based on scientific advances that have accumulated since our last assessment (Photochem and Photobiol Sci 20(1):1–67, 2021). We also discuss how climate change affects stratospheric ozone depletion and ultraviolet radiation, and how stratospheric ozone depletion affects climate change. The resulting interlinking effects of stratospheric ozone depletion, UV radiation, and climate change are assessed in terms of air quality, carbon sinks, ecosystems, human health, and natural and synthetic materials. We further highlight potential impacts on the biosphere from extreme climate events that are occurring with increasing frequency as a consequence of climate change. These and other interactive effects are examined with respect to the benefits that the Montreal Protocol and its Amendments are providing to life on Earth by controlling the production of various substances that contribute to both stratospheric ozone depletion and climate change.