The influence of long term trends in pollutant emissions on deposition of sulphur and nitrogen and exceedance of critical loads in the United Kingdom

In the United Kingdom, as with other European countries, land-based emissions of NOX and SO2 have fallen significantly over the last few decades. SO2 emissions fell from a peak of 3185 Gg S in 1970 to 344 Gg S in 2005 and are forecast by business-as-usual emissions scenarios to fall to 172 Gg by 2020. NOX emissions were at a maximum of 951 Gg N in 1970 and fell to 378 by 2005 with a further decrease to 243 Gg N forecast by 2020. These large changes in emissions have not been matched by emissions changes for NH3 which decreased from 315 Gg N in 1990 to 259 in 2005 and are forecast to fall to 222 by 2020. The Fine Resolution Atmospheric Multi-pollutant Exchange model (FRAME) has been applied to model the spatial distribution of sulphur and nitrogen deposition over the United Kingdom during a 15 year time period (1990-2005) and compared with measured deposition of sulphate, nitrate and ammonium from the national monitoring network. Wet deposition of nitrogen and sulphur was found to decrease more slowly than the emissions reductions rate. This is attributed to a number of factors including increases in emissions from international shipping and changing rates of atmospheric oxidation. The modelled time series was extended to a 50 year period from 1970 to 2020. The modelled deposition of SOx, NOy and NHx to the UK was found to fall by 87%, 52% and 25% during this period. The percentage of the United Kingdom surface area for which critical loads are exceeded is estimated to fall from 85% in 1970 to 37% in 2020 for acidic deposition and from 73% to 49% for nutrient nitrogen deposition. The significant reduction in land emissions of SO2 and NOX focuses further attention in controlling emissions from international shipping. Future policies to control emissions of ammonia from agriculture will be required to effect further significant reductions in nitrogen deposition

IFN-λ3, not IFN-λ4, likely mediates IFNL3–IFNL4 haplotype–dependent hepatic inflammation and fibrosis

The International Liver Disease Genetics Consortium (ILDGC).Genetic variation in the IFNL3–IFNL4 (interferon-λ3–interferon-λ4) region is associated with hepatic inflammation and fibrosis1,2,3,4. Whether IFN-λ3 or IFN-λ4 protein drives this association is not known. We demonstrate that hepatic inflammation, fibrosis stage, fibrosis progression rate, hepatic infiltration of immune cells, IFN-λ3 expression, and serum sCD163 levels (a marker of activated macrophages) are greater in individuals with the IFNL3–IFNL4 risk haplotype that does not produce IFN-λ4, but produces IFN-λ3. No difference in these features was observed according to genotype at rs117648444, which encodes a substitution at position 70 of the IFN-λ4 protein and reduces IFN-λ4 activity, or between patients encoding functionally defective IFN-λ4 (IFN-λ4–Ser70) and those encoding fully active IFN-λ4–Pro70. The two proposed functional variants (rs368234815 and rs4803217)5,6 were not superior to the discovery SNP rs12979860 with respect to liver inflammation or fibrosis phenotype. IFN-λ3 rather than IFN-λ4 likely mediates IFNL3–IFNL4 haplotype–dependent hepatic inflammation and fibrosis.M.E., M.D., and J.G. are supported by the Robert W. Storr Bequest to the Sydney Medical Foundation, University of Sydney, and by a National Health and Medical Research Council of Australia (NHMRC) Program Grant (1053206) and NHMRC Project Grants (APP1107178 and APP1108422). G.D. is supported by an NHMRC Fellowship (1028432)

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

The impact of precipitation on wet deposition of sulphur and nitrogen compounds

Atmospheric transport model FRAME has been used in this study to estimate the influence of precipitation on the patterns of wet deposition of oxidised sulphur, oxidised nitrogen and reduced nitrogen in Poland during the years 1981-2005. A constant wind and emission data and year-specific spatially interpolated precipitation data was used in the model. The results show that the correlation coefficient between mean annual precipitation totals and mean wet deposition is above 0.9 for all examined compounds. The spatial patterns of pollutant deposition are similar for all years, with the north-western part of Poland receiving the lowest and the southern, mountainous part, the highest pollutant load. The largest precipitation-induced changes in wet deposition budgets are observed for oxidised sulphur (53% of the average amount between wet and dry year), and smaller for oxidised and reduced nitrogen (30%). Inter-annual precipitation changes cause large variations in the amount of wet deposition of pollutants. This means that the emission abatements may not cause immediate environmental effects, eg reductions in deposition of pollutants and, further ecosystems areas of exceeded critical loads

Fine-Resolution Modeling of Concentration and Deposition of Nitrogen and Sulphur Compounds for Poland - Application of the FRAME Model

The main source of spatial information on concentration and deposition of air pollutants in Poland is the continental scale EMEP model with 50km x 50km grid. The coarse resolution of the EMEP model may be insufficient for regional scale studies. A new proposal is the application of the national scale atmospheric transport model FRAME (Fine Resolution Atmospheric Multi-pollutant Exchange), originally developed for the United Kingdom. The model works with 5km x 5km spatial resolution and the air column is divided into 33 layers. FRAME was used here to asses the spatial patterns of yearly averaged air concentrations, and wet and dry deposition of sulphur and nitrogen compounds for the area of Poland. This study presents preliminary results of the modelling of the yearly average concentrations as well as dry and wet deposition of SOx, NOy and NHx for Poland. FRAME results were compared with available measurements from the monitoring sites and national deposition budget with the EMEP and IMGW estimates. The results show close agreement with the measured concentrations expressed by determination coefficient close to 0.7 for both SO2 and NOx. The dry and wet deposition budgets for FRAME are also in close agreement with the EMEP and GIOŚ estimates. The FRAME model, despite its relatively simple meteorological parameterisations, is well suited to calculate the spatial pattern of annual average concentration and yearly deposition of atmospheric pollutants which was earlier presented for the UK and was shown in this paper for Poland. The model can also be used to analyse the impact of individual point sources or different emission sectors on spatial pattern of air concentration and deposition as well as testing the changes in deposition resulting from future emissions reduction scenarios