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Objective. To assess whether preliminary findings of associations between the HLA-DRB1*04 and HLA-DRB1* shared epitope (SE) allelic groups and response to the anti-IL-17A mAb secukinumab in RA were reproducible in an independent RA cohort. Methods. Biologic-naïve subjects (n = 100) with RA by 2010 criteria with tender/swollen joint counts (each 56) and high-sensitivity CRP (hsCRP) >10mg/l were randomized 2:1 to secukinumab 10mg/kg i.v. or placebo every 2 weeks until week 10. Potential associations with treatment response to secukinumab at week 12 (DAS28-CRP change from baseline by analysis of covariance, ACR20 response rate by logistic regression) were assessed for HLA-DRB1*04 (primary end point), HLA-DRB1*SE and HLA-DRB1 position 11 V/L (HLA-DRB1*pos11 V/L) allelic groups, and baseline levels of hsCRP, RF and anti-CCP. Results. Secukinumab was significantly more effective than placebo in reducing DAS28-CRP (2.41 vs0.71; P<0.0001) and producing ACR20 responses (87.1% vs 25.0%; P<0.0001) at week 12. The HLA-DRB1*04 allelic group was not significantly related to secukinumab response vs placebo. For change from baseline in DAS28-CRP, HLA-DRB1*SE (P = 0.003) and HLA-DRB1*pos11 V/L (P = 0.002) allelic groups were associated with positive treatment response. Higher RF levels, but not anti-CCP positivity, were significantly associated with DAS28-CRP reductions (P = 0.015) and ACR20 (P = 0.008) responses. Secukinumab was well tolerated. Conclusion. Secukinumab significantly reduced signs and symptoms of RA vs placebo. As the HLA-DRB1*SE and HLA-DRB1*pos11 V/L results were driven by lack of placebo response in carriers, the hypothesis of clinical utility for HLA-DRB1* allelic groups in RA anti-IL-17A short-term response prediction could not be corroborated. Trial registration: ClinicalTrials.gov; https://clinicaltrials.gov/; NCT01426789. [ABSTRACT FROM AUTHOR]

Using a theoretical model and mass isotopic balance, biogas (methane and CO2) released from buried products at their microbial degradation was analysed in the landfill of municipal and non-toxic industrial solid organic waste near Kaluga city, Russia. The landfill contains about 1.34×106 tons of waste buried using a 'sandwich technique' (successive application of sand-clay and waste layers). The δ13C values of biogenic methane with respect to CO2 were-56.8 (±2.5) ‰, whereas the δ13C of CO2 peaked at+9.12‰ (+1.4±2.3‰ on average), reflecting a virtual fractionation of carbon isotopes in the course of bacterial CO2 reduction at the landfill body. After passing through the aerated soil layers, methane was partially oxidised and characterised by δ13C in the range of-50.6 to-38.2‰, evidencing enrichment in 13C, while the released carbon dioxide had δ13C of-23.3 to-4.04‰, respectively. On the mass isotopic balance for the δ13C values, the methane production in the landfill anaerobic zone and the methane emitted through the aerated landfill surface to the atmosphere, the portion of methane oxidised by methanotrophic bacteria was calculated to be from 10 to 40% (averaged about 25%). According to the theoretical estimation and field measurements, the annual rate of methane production in the landfill reached about 2.9(±1.4)×109 g C CH4 yr-1 or 5.3(±2.6)×106 m3 CH4 yr-1. The average rates of methane production in the landfill and methane emission from landfill to the atmosphere are estimated as about 53 (±26) g C CH4 m-2 d-1 (or 4 (±2) mol CH4 m-2 d-1) and 33 (±12) g C CH4 m-2 d-1 (or 2.7 (±1) mol CH4 m-2 d-1), respectively. The calculated part of methane consumed by methanotrophic bacteria in the aerated part of the landfill was 13(±7) g C CH4 m-2 d-1 (or 1.1(±0.6) mol CH4 m-2 d-1) on average. [ABSTRACT FROM AUTHOR]