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The oxygen isotope composition of atmospheric carbon dioxide (CO2) is intimately linked to large-scale variations in the cycling of CO2 and water across the Earth's surface. Understanding the role the biosphere plays in modifying the oxygen isotope composition of atmospheric CO2 is particularly important as this isotopic tracer has the potential to constrain estimates of important processes such as gross primary production at large scales. However, constraining the atmospheric mass budget for the oxygen isotope composition of CO2 also requires that we understand better the contribution of soil communities and how they influence the rate of oxygen isotope exchange between soil water and CO2 (kiso) across a wide range of soil types and climatic zones. As the carbonic anhydrases (CAs) group of enzymes enhances the rate of CO2 hydration within the water-filled pore spaces of soils, it is important to develop understanding of how environmental drivers can impact kiso through changes in their activity. Here we estimate kiso and measure associated soil properties in laboratory incubation experiments using 44 soils sampled from sites across western Eurasia and north-eastern Australia. Observed values for kiso always exceeded theoretically derived uncatalysed rates, indicating a significant influence of CAs on the variability of kiso across the soils studied. We identify soil pH as the principal source of variation, with greater kiso under alkaline conditions suggesting that shifts in microbial community composition or intra–extra-cellular dissolved inorganic carbon gradients induce the expression of more or higher activity forms of CAs. We also show for the first time in soils that the presence of nitrate under naturally acidic conditions reduces kiso, potentially reflecting a direct or indirect inhibition of CAs. This effect appears to be supported by a supplementary ammonium nitrate fertilisation experiment conducted on a subset of the soils. Greater microbial biomass also increased kiso under a given set of chemical conditions, highlighting a putative link between CA expression and the abundance of soil microbes. These data provide the most extensive analysis of spatial variations in soil kiso to date and indicate the key soil trait datasets required to predict variations in kiso at large spatial scales, a necessary next step to constrain the important role of soil communities in the atmospheric mass budget of the oxygen isotope composition of CO2.

Abstract Chronic obstructive pulmonary disease (COPD) treatment guidelines do not currently include recommendations for escalation directly from monotherapy to triple therapy. This 12-week, double-blind, double-dummy study randomized 800 symptomatic moderate-to-very-severe COPD patients receiving tiotropium (TIO) for ≥3 months to once-daily fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) 100/62.5/25 mcg via ELLIPTA (n = 400) or TIO 18 mcg via HandiHaler (n = 400) plus matched placebo. Study endpoints included change from baseline in trough forced expiratory volume in 1 s (FEV1) at Days 85 (primary), 28 and 84 (secondary), health status (St George’s Respiratory Questionnaire [SGRQ] and COPD Assessment Test [CAT]) and safety. FF/UMEC/VI significantly improved trough FEV1 at all timepoints (Day 85 treatment difference [95% CI] 95 mL [62–128]; P

Abstract Background This analysis of the IMPACT study assessed the cardiovascular (CV) safety of single-inhaler triple therapy with fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) versus FF/VI and UMEC/VI dual therapy. Methods IMPACT was a 52-week, randomized, double-blind, multicenter Phase III study comparing the efficacy and safety of FF/UMEC/VI 100/62.5/25 mcg with FF/VI 100/25 mcg or UMEC/VI 62.5/25 mcg in patients ≥40 years of age with symptomatic chronic obstructive pulmonary disease (COPD) and ≥1 moderate/severe exacerbation in the previous year. The inclusion criteria for the study were intentionally designed to permit the enrollment of patients with significant concurrent CV disease/risk. CV safety assessments included proportion of patients with and exposure-adjusted rates of on-treatment CV adverse events of special interest (CVAESI) and major adverse cardiac events (MACE), as well as time-to-first (TTF) CVAESI, and TTF CVAESI resulting in hospitalization/prolonged hospitalization or death. Results Baseline CV risk factors were similar across treatment groups. Overall, 68% of patients (n = 7012) had ≥1 CV risk factor and 40% (n = 4127) had ≥2. At baseline, 29% of patients reported a current/past cardiac disorder and 58% reported a current/past vascular disorder. The proportion of patients with on-treatment CVAESI was 11% for both FF/UMEC/VI and UMEC/VI, and 10% for FF/VI. There was no statistical difference for FF/UMEC/VI versus FF/VI or UMEC/VI in TTF CVAESI (hazard ratio [HR]: 0.98, 95% confidence interval [CI]: 0.85, 1.11; p = 0.711 and HR: 0.92, 95% CI: 0.78, 1.08; p = 0.317, respectively) nor TTF CVAESI leading to hospitalization/prolonged hospitalization or death (HR: 1.19, 95% CI: 0.93, 1.51; p = 0.167 and HR: 0.96, 95% CI: 0.72, 1.27; p = 0.760, respectively). On-treatment MACE occurred in ≤3% of patients across treatment groups, with similar prevalence and rates between treatments. Conclusions In a symptomatic COPD population with a history of exacerbations and a high rate of CV disease/risk, the proportion of patients with CVAESI and MACE was 10–11% and 1–3%, respectively, across treatment arms, and the risk of CVAESI was low and similar across treatment arms. There was no statistically significant increased CV risk associated with the use of FF/UMEC/VI versus FF/VI or UMEC/VI, and UMEC/VI versus FF/VI. Trial registration NCT02164513 (GSK study number CTT116855).

Abstract Background The comparative efficacy of inhaled corticosteroid/long-acting muscarinic antagonist/long-acting β2-agonist (ICS/LAMA/LABA) triple therapy administered via single or multiple inhalers in patients with chronic obstructive pulmonary disease (COPD) has not been evaluated comprehensively. We conducted two replicate trials comparing single- with multiple-inhaler ICS/LAMA/LABA combination in COPD. Methods 207608 and 207609 were Phase IV, 12-week, randomized, double-blind, triple-dummy non-inferiority trials comparing once-daily fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) 100/62.5/25 μg via Ellipta inhaler, with twice-daily budesonide/formoterol (BUD/FOR) 400/12 μg via metered-dose inhaler plus once-daily tiotropium (TIO) 18 μg via HandiHaler. Patients had symptomatic COPD and forced expiratory volume in 1 s (FEV1)

Drought conditions can alter the composition of soil microbial communities, but the effects of drought on network properties have not been tested. Here, de Vries and colleagues show that co-occurrence networks are destabilised under drought for bacteria but not fungi.

Soils both emit and consume the trace gas carbonyl sulfide (COS) leading to a soil–air COS exchange rate that is the net result of two opposing fluxes. Partitioning these two gross fluxes and understanding their drivers are necessary to estimate the contribution of soils to the current and future atmospheric COS budget.Previous efforts to disentangle the gross COS fluxes from soils have used flux measurements on air-dried soils as a proxy for the COS emission rates of moist soils. However, this method implicitly assumes that COS uptake becomes negligible and that COS emission remains steady while soils are drying. We tested this assumption by simultaneously estimating the soil COS sources and sinks and their temperature sensitivity (Q10); these estimates were based on soil–air COS flux measurements on fresh soils at different COS concentrations and two soil temperatures. Measurements were performed on 27 European soils from different biomes and land use types in order to obtain a large range of physical–chemical properties and identify the drivers of COS consumption and production rates.We found that COS production rates from moist and air-dried soils were not significantly different for a given soil and that the COS production rates had Q10 values (3.96 ± 3.94) that were larger and more variable than the Q10 for COS consumption (1.17 ± 0.27). COS production generally contributed less to the net flux at lower temperatures but this contribution of COS production increased rapidly at higher temperatures, lower soil moisture contents and lower COS concentrations. Consequently, measurements at higher COS concentrations (viz. 1000 ppt) always increased the robustness of COS consumption estimates. Across the range of biomes and land use types COS production rates co-varied with total soil nitrogen concentrations (r = 0.52, P r = 0.53, P r = −0.74 and 0.64, P P

Aim: This study aim was to evaluate if patients with type 2 diabetes and osteoporosis have an increased risk of periodontal disease (horizontal and vertical bone loss) when compared to diabetic patients without osteoporosis. Additionally, to assess if patients with diabetes and osteoporosis have a greater risk of reduction of bone mineral density in the mandible, expressed by mandibular cortical index (MCI) when compared to diabetic patients without osteoporosis. Methods: 59 patients (39 diagnosed with type 2 diabetes and osteoporosis; 20 diagnosed with type 2 diabetes and without osteoporosis) were selected. Type 2 diabetes was previously diagnosed by glycated hemoglobin examination and osteoporosis by peripheral dual-energy x-ray absorptiometry. Mandibular cortical index, as well as the presence of vertical and horizontal bone loss was verified on panoramic radiographs. Adjusted odds ratio analyses were performed on presence of periodontal disease and MCI considering the effect of osteoporosis. Results: Absence of statistical significance between variables was found. Conclusions: There is no difference between the risk of periodontal disease or low MCI among osteoporotic and non-osteoporotic type 2 diabetic patients.