Organic Reference Materials for Hydrogen, Carbon, and Nitrogen Stable Isotope-Ratio Measurements: Caffeines, n-Alkanes, Fatty Acid Methyl Esters, Glycines, L-Valines, Polyethylenes, and Oils

An international project developed, quality-tested, and determined isotope−δ values of 19 new organic reference materials (RMs) for hydrogen, carbon, and nitrogen stable isotope-ratio measurements, in addition to analyzing pre-existing RMs NBS 22 (oil), IAEA-CH-7 (polyethylene foil), and IAEA-600 (caffeine). These new RMs enable users to normalize measurements of samples to isotope−δ scales. The RMs span a range of δ^2H_(VSMOW-SLAP) values from −210.8 to +397.0 mUr or ‰, for δ^(13)C_(VPDB-LSVEC) from −40.81 to +0.49 mUr and for δ^(15)N_(Air) from −5.21 to +61.53 mUr. Many of the new RMs are amenable to gas and liquid chromatography. The RMs include triads of isotopically contrasting caffeines, C_(16) n-alkanes, n-C_(20)-fatty acid methyl esters (FAMEs), glycines, and L-valines, together with polyethylene powder and string, one n-C_(17)-FAME, a vacuum oil (NBS 22a) to replace NBS 22 oil, and a ^2H-enriched vacuum oil. A total of 11 laboratories from 7 countries used multiple analytical approaches and instrumentation for 2-point isotopic normalization against international primary measurement standards. The use of reference waters in silver tubes allowed direct normalization of δ2H values of organic materials against isotopic reference waters following the principle of identical treatment. Bayesian statistical analysis yielded the mean values reported here. New RMs are numbered from USGS61 through USGS78, in addition to NBS 22a. Because of exchangeable hydrogen, amino acid RMs currently are recommended only for carbon- and nitrogen-isotope measurements. Some amino acids contain ^(13)C and carbon-bound organic ^2H-enrichments at different molecular sites to provide RMs for potential site-specific isotopic analysis in future studies

Reviews and syntheses: A framework to observe, understand and project ecosystem response to environmental change in the East Antarctic Southern Ocean

Abstract. Systematic long-term studies on ecosystem dynamics are largely lacking from the East Antarctic Southern Ocean, although it is well recognized that they are indispensable to identify the ecological impacts and risks of environmental change. Here, we present a framework for establishing a long-term cross-disciplinary study on decadal timescales. We argue that the eastern Weddell Sea and the adjacent sea to the east, off Dronning Maud Land, is a particularly well suited area for such a study, since it is based on findings from previous expeditions to this region. Moreover, since climate and environmental change have so far been comparatively muted in this area, as in the eastern Antarctic in general, a systematic long-term study of its environmental and ecological state can provide a baseline of the current situation, which will be important for an assessment of future changes from their very onset, with consistent and comparable time series data underpinning and testing models and their projections. By establishing an Integrated East Antarctic Marine Research (IEAMaR) observatory, long-term changes in ocean dynamics, geochemistry, biodiversity, and ecosystem functions and services will be systematically explored and mapped through regular autonomous and ship-based synoptic surveys. An associated long-term ecological research (LTER) programme, including experimental and modelling work, will allow for studying climate-driven ecosystem changes and interactions with impacts arising from other anthropogenic activities. This integrative approach will provide a level of long-term data availability and ecosystem understanding that are imperative to determine, understand, and project the consequences of climate change and support a sound science-informed management of future conservation efforts in the Southern Ocean. </jats:p

The TNFR1 antagonist Atrosimab is therapeutic in mouse models of acute and chronic inflammation

Therapeutics that block tumor necrosis factor (TNF), and thus activation of TNF receptor 1 (TNFR1) and TNFR2, are clinically used to treat inflammatory diseases such as rheumatoid arthritis, inflammatory bowel disease and psoriasis. However, TNFR1 and TNFR2 work antithetically to balance immune responses involved in inflammatory diseases. In particular, TNFR1 promotes inflammation and tissue degeneration, whereas TNFR2 contributes to immune modulation and tissue regeneration. We, therefore, have developed the monovalent antagonistic anti-TNFR1 antibody derivative Atrosimab to selectively block TNFR1 signaling, while leaving TNFR2 signaling unaffected. Here, we describe that Atrosimab is highly stable at different storage temperatures and demonstrate its therapeutic efficacy in mouse models of acute and chronic inflammation, including experimental arthritis, non-alcoholic steatohepatitis (NASH) and experimental autoimmune encephalomyelitis (EAE). Our data support the hypothesis that it is sufficient to block TNFR1 signaling, while leaving immune modulatory and regenerative responses via TNFR2 intact, to induce therapeutic effects. Collectively, we demonstrate the therapeutic potential of the human TNFR1 antagonist Atrosimab for treatment of chronic inflammatory diseases

Patterns of Alcohol Consumption Among Individuals With Alcohol Use Disorder During the COVID-19 Pandemic and Lockdowns in Germany

Importance Alcohol consumption (AC) leads to death and disability worldwide. Ongoing discussions on potential negative effects of the COVID-19 pandemic on AC need to be informed by real-world evidence. Objective To examine whether lockdown measures are associated with AC and consumption-related temporal and psychological within-person mechanisms. Design, Setting, and Participants This quantitative, intensive, longitudinal cohort study recruited 1743 participants from 3 sites from February 20, 2020, to February 28, 2021. Data were provided before and within the second lockdown of the COVID-19 pandemic in Germany: before lockdown (October 2 to November 1, 2020); light lockdown (November 2 to December 15, 2020); and hard lockdown (December 16, 2020, to February 28, 2021). Main Outcomes and Measures Daily ratings of AC (main outcome) captured during 3 lockdown phases (main variable) and temporal (weekends and holidays) and psychological (social isolation and drinking intention) correlates. Results Of the 1743 screened participants, 189 (119 [63.0%] male; median [IQR] age, 37 [27.5-52.0] years) with at least 2 alcohol use disorder (AUD) criteria according to the Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition) yet without the need for medically supervised alcohol withdrawal were included. These individuals provided 14 694 smartphone ratings from October 2020 through February 2021. Multilevel modeling revealed significantly higher AC (grams of alcohol per day) on weekend days vs weekdays (β = 11.39; 95% CI, 10.00-12.77; P < .001). Alcohol consumption was above the overall average on Christmas (β = 26.82; 95% CI, 21.87-31.77; P < .001) and New Year’s Eve (β = 66.88; 95% CI, 59.22-74.54; P < .001). During the hard lockdown, perceived social isolation was significantly higher (β = 0.12; 95% CI, 0.06-0.15; P < .001), but AC was significantly lower (β = −5.45; 95% CI, −8.00 to −2.90; P = .001). Independent of lockdown, intention to drink less alcohol was associated with lower AC (β = −11.10; 95% CI, −13.63 to −8.58; P < .001). Notably, differences in AC between weekend and weekdays decreased both during the hard lockdown (β = −6.14; 95% CI, −9.96 to −2.31; P = .002) and in participants with severe AUD (β = −6.26; 95% CI, −10.18 to −2.34; P = .002). Conclusions and Relevance This 5-month cohort study found no immediate negative associations of lockdown measures with overall AC. Rather, weekend-weekday and holiday AC patterns exceeded lockdown effects. Differences in AC between weekend days and weekdays evinced that weekend drinking cycles decreased as a function of AUD severity and lockdown measures, indicating a potential mechanism of losing and regaining control. This finding suggests that temporal patterns and drinking intention constitute promising targets for prevention and intervention, even in high-risk individuals

Reviews and syntheses: A framework to observe, understand, and project ecosystem response to environmental change in the East Antarctic Southern Ocean

Systematic long-term studies on ecosystem dynamics are largely lacking for the East Antarctic Southern Ocean, although it is well recognized that such investigations are indispensable to identify the ecological impacts and risks of environmental change. Therefore, here we develop a framework for establishing a long-term cross-disciplinary study and argue why the eastern Weddell Sea and the easterly adjacent sea off Dronning Maud Land (WSoDML) is a well suited area for such an initiative. As in the Eastern Antarctic in general, climate and environmental change have so far been comparatively muted in this area. A systematic long-term study of its environmental and ecological state can thus provide a baseline of the current situation, an assessment of future changes, and sound data can act as a model to develop and calibrate projections. Establishing a long-term observation (LTO) and long-term ecological research (LTER) programme now would allow the study of climate-driven ecosystem changes and interactions with impacts arising from other anthropogenic activities, from their very onset. Through regular autonomous and ship-based LTO activities, changes in ocean dynamics, geochemistry, biodiversity and ecosystem functions and services can be systematically explored and mapped. This observational work should be accompanied by targeted LTER efforts, including experimental and modelling studies. This approach will provide a level of long-term data availability and ecosystem understanding that are imperative to determine, understand, and project the consequences of climate change and support a sound science-informed management of future conservation efforts in the Southern Ocean

The Year of Polar Prediction in the Southern Hemisphere (YOPP-SH)

The Year of Polar Prediction in the Southern Hemisphere (YOPP-SH) had a Special Observing Period (SOP) that ran from November 16, 2018 to February 15, 2019, a period chosen to span the austral warm season months of greatest operational activity in the Antarctic. Some 2200 additional radiosondes were launched during the 3-month SOP, roughly doubling the routine program, and the network of drifting buoys in the Southern Ocean was enhanced. An evaluation of global model forecasts during the SOP and using its data has confirmed that extratropical Southern Hemisphere forecast skill lags behind that in the Northern Hemisphere with the contrast being greatest between the southern and northern polar regions. Reflecting the application of the SOP data, early results from observing system experiments show that the additional radiosondes