Design and baseline characteristics of the finerenone in reducing cardiovascular mortality and morbidity in diabetic kidney disease trial

Background: Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. Patients and Methods: The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate >= 25 mL/min/1.73 m(2) and albuminuria (urinary albumin-to-creatinine ratio >= 30 to <= 5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level alpha = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. Conclusions: FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049

Visualization of subcutaneous insulin injections by x-ray computed tomography

We report how the three-dimensional structure of subcutaneous injections of soluble insulin can be visualized by x-ray computed tomography using an iodine based contrast agent. The injections investigated are performed ex vivo in porcine adipose tissue. Full tomography scans carried out at a laboratory x-ray source with a total acquisition time of about 1 min yield CT-images with an effective pixel size of 109 × 109 μm2. The depots are segmented using a modified Chan–Vese algorithm and we are able to observe differences in the shape of the injection depot and the position of the depot in the skin among equally performed injections. To overcome the beam hardening artefacts, which affect the quantitative prediction of the volume injected, we additionally present results concerning the visualization of two injections using synchrotron radiation. The spatial concentration distribution of iodine is calculated to show the dilution of the insulin drug inside the depot. Characterisation of the shape of the depot and the spatial concentration profile of the injected fluid is important knowledge when improving the clinical formulation of an insulin drug, the performance of injection devices and when predicting the effect of the drug through biomedical simulations

Variability in gaseous elemental mercury at Villum Research Station, Station Nord, in North Greenland from 1999 to 2017

Special issue Research results from the 14th International Conference on Mercury as a Global Pollutant (ICMGP 2019), MercOx project, and iGOSP and iCUPE projects of ERA-PLANET in support of the Minamata Convention on Mercury (ACP/AMT inter-journal SI).-- 13 pages, 9 figures, 1 tableMercury is ubiquitous in the atmosphere, and atmospheric transport is an important source for this element in the Arctic. Measurements of gaseous elemental mercury (GEM) have been carried out at Villum Research Station (Villum) at Station Nord, situated in northern Greenland. The measurements cover the period 1999–2017, with a gap in the data for the period 2003–2008 (for a total of 11 years). The measurements were compared with model results from the Danish Eulerian Hemispheric Model (DEHM) that describes the contribution from direct anthropogenic transport, marine emissions and general background concentration. The percentage of time spent over different surfaces was calculated by back-trajectory analysis, and the reaction kinetics were determined by a comparison with ozone. The GEM measurements were analysed for trends, both seasonal and annual. The only significant trends found were negative ones for the winter and autumn months. Comparison of the measurements to simulations using the Danish Eulerian Hemispheric Model (DEHM) indicated that direct transport of anthropogenic emissions of mercury accounts for between 14 % and 17 % of the measured mercury. Analysis of the kinetics of the observed atmospheric mercury depletion events (AMDEs) confirms the results of a previous study at Villum of the competing reactions of GEM and ozone with Br, which suggests that the lifetime of GEM is about a month. However, a GEM lifetime of 12 months gave the best agreement between the model and measurements. The chemical lifetime is shorter, and thus, the apparent lifetime appears to be the result of deposition followed by reduction and re-emission; for this reason, the term “relaxation time” is preferred to “lifetime” for GEM. The relaxation time for GEM causes a delay between emission reductions and the effect on actual concentrations. No significant annual trend was found for the measured concentrations of GEM over the measurement period, despite emission reductions. This is interesting, and together with low direct transport of GEM to Villum as found by the DEHM model, it shows that the dynamics of GEM are very complex. Therefore, in the coming years, intensive measurement networks are needed to describe the global distribution of mercury in the environment as the use of models to predict future levels will still be highly uncertain. The situation is increasingly complex due to global changes that most likely will change the transport patterns of mercury, not only in the atmosphere but also between matrixesThis research has been supported by the Danish Environmental Protection Agency (DANCEA funds for Environmental Support to the Arctic Region project; grant no. 2019-7975) and by the European ERA-PLANET projects of iGOSP and iCUPE (consortium agreement no. 689443 for both projects)With the funding support of the ‘Severo Ochoa Centre of Excellence’ accreditation (CEX2019-000928-S), of the Spanish Research Agency (AEI)Peer reviewe

Nitrogen Deposition on Danish Nature

Eutrophication events are frequent in Inner Danish waters and critical loads are exceeded for much of the Danish sensitive terrestrial ecosystems. The Danish air quality monitoring program combines measurements and model calculations to benefit from the complementarities in data from these two sources. Measurements describe actual status, seasonal variation, and temporal trends. Model calculations extrapolate the results to the entire country and determine depositions to specific ecosystems. Measurements in 2016 show annual depositions between 7.5 and 11 kg N/ha to terrestrial ecosystems, and a load to marine waters of 5.3 kg N/ha. The deposition on Danish marine waters in 2016 was calculated to be 73,000 tons N with an average deposition of 6.9 kg N/ha. For terrestrial areas, the deposition was calculated to be 57,000 tons N with an average deposition of 13 kg N/ha. This is above critical loads for sensitive ecosystems. Long-term trends show a 35% decrease since 1990 in measured annual nitrogen deposition. At two out of four stations in nature areas, measured ammonia levels exceeded critical levels for lichens and mosses. Conclusions: Nitrogen loads and levels to Danish nature is decreasing, but critical loads and levels are still exceeded for sensitive ecosystems. Combining measurements and model calculations is a strong tool in monitoring

Association of light-to-moderate alcohol drinking in pregnancy with preterm birth and birth weight:elucidating bias by pooling data from nine European cohorts

International audienceWomen who drink light-to-moderately during pregnancy have been observed to have lower risk of unfavourable pregnancy outcomes than abstainers. This has been suggested to be a result of bias. In a pooled sample, including 193 747 live-born singletons from nine European cohorts, we examined the associations between light-to-moderate drinking and preterm birth, birth weight, and small-for-gestational age in term born children (term SGA). To address potential sources of bias, we compared the associations from the total sample with a sub-sample restricted to first-time pregnant women who conceived within six months of trying, and examined whether the associations varied across calendar time. In the total sample, drinking up to around six drinks per week as compared to abstaining was associated with lower risk of preterm birth, whereas no significant associations were found for birth weight or term SGA. Drinking six or more drinks per week was associated with lower birth weight and higher risk of term SGA, but no increased risk of preterm birth. The analyses restricted to women without reproductive experience revealed similar results. Before 2000 approximately half of pregnant women drank alcohol. This decreased to 39% in 2000–2004, and 14% in 2005–2011. Before 2000, every additional drink was associated with reduced mean birth weight, whereas in 2005–2011, the mean birth weight increased with increasing intake. The period-specific associations between low-to-moderate drinking and birth weight, which also were observed for term SGA, are indicative of bias. It is impossible to distinguish if the bias is attributable to unmeasured confounding, which change over time or cohort heterogeneity. © 2017, Springer Science+Business Media B.V

Association of light-to-moderate alcohol drinking in pregnancy with preterm birth and birth weight: elucidating bias by pooling data from nine European cohorts

Women who drink light-to-moderately during pregnancy have been observed to have lower risk of unfavourable pregnancy outcomes than abstainers. This has been suggested to be a result of bias. In a pooled sample, including 193 747 live-born singletons from nine European cohorts, we examined the associations between light-to-moderate drinking and preterm birth, birth weight, and small-for-gestational age in term born children (term SGA). To address potential sources of bias, we compared the associations from the total sample with a sub-sample restricted to first-time pregnant women who conceived within six months of trying, and examined whether the associations varied across calendar time. In the total sample, drinking up to around six drinks per week as compared to abstaining was associated with lower risk of preterm birth, whereas no significant associations were found for birth weight or term SGA. Drinking six or more drinks per week was associated with lower birth weight and higher risk of term SGA, but no increased risk of preterm birth. The analyses restricted to women without reproductive experience revealed similar results. Before 2000 approximately half of pregnant women drank alcohol. This decreased to 39% in 2000–2004, and 14% in 2005–2011. Before 2000, every additional drink was associated with reduced mean birth weight, whereas in 2005–2011, the mean birth weight increased with increasing intake. The period-specific associations betw