Sr-Nd-Pb isotopic systematic and geochronology of ultramafic alkaline magmatism of the southwestern margin of the Siberian Craton: Metasomatism of the sub-continental lithospheric mantle related to subduction and plume events

© 2020 To provide new insights into the origin and evolution of ultramafic lamprophyres (UMLs) and their mantle source, we examined two UML (aillikite and damtjernite) occurrences of different ages in the western portion of the Siberian Craton (Ilbokich and Chadobets). New age, mineral and rock geochemistry, along with Sr–Nd–Pb–C–O isotope data was obtained. Our new 206Pb/238U perovskite age (399 ± 4 Ma) confirms the previously published Early Devonian age of the Ilbokich aillikite. Rb[sbnd]Sr isochron and 40Ar/39Ar dating yielded a Middle Triassic age (243 ± 3 Ma and 241 ± 1 Ma, respectively) for the Chadobets aillikites, indicating post-Trap emplacement of these rocks. Both UMLs are characterized by incompatible elements, including light rare earth element (LREE) enrichments (La is up to ×200 chondrite concentration), and strong fractionation of REEs ((La/Yb)n: 33–84). Despite the close geochemical affinity of both UMLs, the Nd isotopic compositions of aillikites, as well as the Pb isotopic composition of Chadobets and Ilbokich UMLs, do not overlap and are distinctly different from each other. The initial Sr and Nd isotopic compositions of the Ilbokich UMLs fall in within a narrow 87Sr/86Sr0 range (0.7032–0.7042) and εNd(T) (4.03–3.97). Chadobets UMLs have a similar Sr isotopic signature (87Sr/86Sr0: 0.7031–0.7043) and a more depleted Nd isotopic signature (εNd(T) 4.09–5.08). The initial Pb isotope compositions of the Chadobets UMLs are moderately radiogenic, ranging between 206Pb/204Pb = 18.4–19.0, 208Pb/204Pb = 38.3–38.8, and are characterized by a narrow 207Pb/204Pb ratio between 15.5 and 15.6. The Ilbokich Pb isotope compositions are less variable and range between 206Pb/204Pb = 18.0–18.4, 208Pb/204Pb = 37.8–38.4 and 207Pb/204Pb ratios between 15.5 and 15.6. The oxygen isotopic composition of carbonate from both UMLs is characterized by highly variable δ18O values from +12.1 and up to +20.5‰ (SMOW). The isotopic composition of δ13C values range from −1.3‰ to −7.1. Based on the minor impact of crustal contamination in both aillikites, it is inferred that their radiogenic isotope composition reflects a mantle source signature. The mantle source of the Chadobets aillikites is likely to include carbonatitic magma as a metasomatic agent. In contrast, phlogopite-rich metasomes within the lithospheric mantle could have contributed more significantly to the Ilbokich aillikites. These metasomes could be formed during the Caledonian orogeny, which did not only affect the southwestern boundary of the Siberian Craton, but also expanded to the craton interior. This study provides additional support for the evolution of the south-western portion of the Siberian SCLM, ranging from mantle containing phlogopite enrichment domains during the Early Devonian to hydrous-phase reduced mantle in the Triassic due to the thermal impact of the Siberian Traps

Antiinflammatory therapy with canakinumab for atherosclerotic disease

BACKGROUND: Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved. METHODS: We conducted a randomized, double-blind trial of canakinumab, a therapeutic monoclonal antibody targeting interleukin-1β, involving 10,061 patients with previous myocardial infarction and a high-sensitivity C-reactive protein level of 2 mg or more per liter. The trial compared three doses of canakinumab (50 mg, 150 mg, and 300 mg, administered subcutaneously every 3 months) with placebo. The primary efficacy end point was nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. RESULTS: At 48 months, the median reduction from baseline in the high-sensitivity C-reactive protein level was 26 percentage points greater in the group that received the 50-mg dose of canakinumab, 37 percentage points greater in the 150-mg group, and 41 percentage points greater in the 300-mg group than in the placebo group. Canakinumab did not reduce lipid levels from baseline. At a median follow-up of 3.7 years, the incidence rate for the primary end point was 4.50 events per 100 person-years in the placebo group, 4.11 events per 100 person-years in the 50-mg group, 3.86 events per 100 person-years in the 150-mg group, and 3.90 events per 100 person-years in the 300-mg group. The hazard ratios as compared with placebo were as follows: in the 50-mg group, 0.93 (95% confidence interval [CI], 0.80 to 1.07; P=0.30); in the 150-mg group, 0.85 (95% CI, 0.74 to 0.98; P=0.021); and in the 300-mg group, 0.86 (95% CI, 0.75 to 0.99; P=0.031). The 150-mg dose, but not the other doses, met the prespecified multiplicity-adjusted threshold for statistical significance for the primary end point and the secondary end point that additionally included hospitalization for unstable angina that led to urgent revascularization (hazard ratio vs. placebo, 0.83; 95% CI, 0.73 to 0.95; P=0.005). Canakinumab was associated with a higher incidence of fatal infection than was placebo. There was no significant difference in all-cause mortality (hazard ratio for all canakinumab doses vs. placebo, 0.94; 95% CI, 0.83 to 1.06; P=0.31). CONCLUSIONS: Antiinflammatory therapy targeting the interleukin-1β innate immunity pathway with canakinumab at a dose of 150 mg every 3 months led to a significantly lower rate of recurrent cardiovascular events than placebo, independent of lipid-level lowering. Copyright © 2017 Massachusetts Medical Society