Clumped Isotopes Link Older Carbon Substrates With Slower Rates of Methanogenesis in Northern Lakes

The release of long‐stored carbon from thawed permafrost could fuel increased methanogenesis in northern lakes, but it remains unclear whether old carbon substrates released from permafrost are metabolized as rapidly by methanogenic microbial communities as recently produced organic carbon. Here, we apply methane (CH₄) clumped isotope (Δ₁₈) and ¹⁴C measurements to test whether rates of methanogenesis are related to carbon substrate age. Results from culture experiments indicate that Δ₁₈ values are negatively correlated with CH₄ production rate. Measurements of ebullition samples from thermokarst lakes in Alaska and glacial lakes in Sweden indicate strong negative correlations between CH₄ Δ₁₈ and the fraction modern carbon. These correlations imply that CH₄ derived from older carbon substrates is produced relatively slowly. Relative rates of methanogenesis, as inferred from Δ₁₈ values, are not positively correlated with CH₄ flux estimates, highlighting the likely importance of environmental variables other than CH₄ production rates in controlling ebullition fluxes

Clumped Isotopes Link Older Carbon Substrates With Slower Rates of Methanogenesis in Northern Lakes

The release of long‐stored carbon from thawed permafrost could fuel increased methanogenesis in northern lakes, but it remains unclear whether old carbon substrates released from permafrost are metabolized as rapidly by methanogenic microbial communities as recently produced organic carbon. Here, we apply methane (CH₄) clumped isotope (Δ₁₈) and ¹⁴C measurements to test whether rates of methanogenesis are related to carbon substrate age. Results from culture experiments indicate that Δ₁₈ values are negatively correlated with CH₄ production rate. Measurements of ebullition samples from thermokarst lakes in Alaska and glacial lakes in Sweden indicate strong negative correlations between CH₄ Δ₁₈ and the fraction modern carbon. These correlations imply that CH₄ derived from older carbon substrates is produced relatively slowly. Relative rates of methanogenesis, as inferred from Δ₁₈ values, are not positively correlated with CH₄ flux estimates, highlighting the likely importance of environmental variables other than CH₄ production rates in controlling ebullition fluxes

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