Effect of induction therapy on the expression of molecular markers associated with rejection and tolerance

Background Induction therapy can improve kidney transplantation (KTx) outcomes, but little is known about the mechanisms underlying its effects. Methods The mRNA levels of T cell-related genes associated with tolerance or rejection (CD247, GZMB, PRF1, FOXP3, MAN1A1, TCAIM, and TLR5) and lymphocyte subpopulations were monitored prospectively in the peripheral blood of 60 kidney transplant recipients before and 7, 14, 21, 28, 60, 90 days, 6 months, and 12 months after KTx. Patients were treated with calcineurin inhibitor- based triple immunosuppression and induction with rabbit anti-thymocyte globulin (rATG, n = 24), basiliximab (n = 17), or without induction (no- induction, n = 19). A generalized linear mixed model with gamma distribution for repeated measures, adjusted for rejection, recipient/donor age and delayed graft function, was used for statistical analysis. Results rATG treatment caused an intense reduction in all T cell type population and natural killer (NK) cells within 7 days, then a slow increase and repopulation was observed. This was also noticed in the expression levels of CD247, FOXP3, GZMB, and PRF1. The basiliximab group exhibited higher CD247, GZMB, FOXP3 and TCAIM mRNA levels and regulatory T cell (Treg) counts than the no-induction group. The levels of MAN1A1 and TLR5 mRNA expressions were increased, whereas TCAIM decreased in the rATG group as compared with those in the no-induction group. Conclusion The rATG induction therapy was associated with decreased T and NK cell-related transcript levels and with upregulation of two rejection- associated transcripts (MAN1A1 and TLR5) shortly after KTx. Basiliximab treatment was associated with increased absolute number of Treg cells, and increased level of FOXP3 and TCAIM expression

Global parameterization and validation of a two-leaf light use efficiency model for predicting gross primary production across FLUXNET sites:TL-LUE Parameterization and Validation

Light use efficiency (LUE) models are widely used to simulate gross primary production (GPP). However, the treatment of the plant canopy as a big leaf by these models can introduce large uncertainties in simulated GPP. Recently, a two-leaf light use efficiency (TL-LUE) model was developed to simulate GPP separately for sunlit and shaded leaves and has been shown to outperform the big-leaf MOD17 model at six FLUX sites in China. In this study we investigated the performance of the TL-LUE model for a wider range of biomes. For this we optimized the parameters and tested the TL-LUE model using data from 98 FLUXNET sites which are distributed across the globe. The results showed that the TL-LUE model performed in general better than the MOD17 model in simulating 8 day GPP. Optimized maximum light use efficiency of shaded leaves (εmsh) was 2.63 to 4.59 times that of sunlit leaves (εmsu). Generally, the relationships of εmsh and εmsu with εmax were well described by linear equations, indicating the existence of general patterns across biomes. GPP simulated by the TL-LUE model was much less sensitive to biases in the photosynthetically active radiation (PAR) input than the MOD17 model. The results of this study suggest that the proposed TL-LUE model has the potential for simulating regional and global GPP of terrestrial ecosystems, and it is more robust with regard to usual biases in input data than existing approaches which neglect the bimodal within-canopy distribution of PAR

Towards long-term standardised carbon and greenhouse gas observations for monitoring Europe's terrestrial ecosystems : a review

Research infrastructures play a key role in launching a new generation of integrated long-term, geographically distributed observation programmes designed to monitor climate change, better understand its impacts on global ecosystems, and evaluate possible mitigation and adaptation strategies. The pan-European Integrated Carbon Observation System combines carbon and greenhouse gas (GHG; CO2, CH4, N2O, H2O) observations within the atmosphere, terrestrial ecosystems and oceans. High-precision measurements are obtained using standardised methodologies, are centrally processed and openly available in a traceable and verifiable fashion in combination with detailed metadata. The Integrated Carbon Observation System ecosystem station network aims to sample climate and land-cover variability across Europe. In addition to GHG flux measurements, a large set of complementary data (including management practices, vegetation and soil characteristics) is collected to support the interpretation, spatial upscaling and modelling of observed ecosystem carbon and GHG dynamics. The applied sampling design was developed and formulated in protocols by the scientific community, representing a trade-off between an ideal dataset and practical feasibility. The use of open-access, high-quality and multi-level data products by different user communities is crucial for the Integrated Carbon Observation System in order to achieve its scientific potential and societal value.Peer reviewe

Alcoholic versus aqueous chlorhexidine for skin antisepsis: the AVALANCHE trial

Background: Preoperative skin antisepsisis routine practice. We compared alcoholic chlorhexidine with aqueous chlorhexidine for skin antisepsis to prevent surgical site infection after minor skin excisions in general practice. Methods: We conducted this prospective, multicentre, randomized controlled trial in 4 private general practices in North Queensland, Australia, from October2015 to August 2016. Consecutive adult patients presenting for minor skin excisions were randomly assigned to undergo preoperative skin antisepsis with 0.5% chlorhexidine in 70% ethanol(intervention) or 0.5% chlorhexidineaqueous solution (control). Our primary outcome was surgical site infection within 30 days of excision. We also measured the incidence of adverse reactions. Results: A total of 916 patients were included in the study: 454 underwent antisepsis with alcoholic chlorhexidine and 462 with aqueous chlorhexidine. Of these, 909 completed follow-up. In the intention-to-treat analysis of cases available at follow-up, there was no significant difference in the incidence of surgical site infection between the alcoholic chlorhexidine arm (5.8%, 95% confidence interval [CI] 3.6% to 7.9%) and the aqueous chlorhexidine arm (6.8%,95% CI 4.5% to 9.1%). The attributable risk reduction was 0.010 (95% CI –0.021to 0.042), the relative risk was 0.85 (95%CI 0.51 to 1.41), and the number needed to treat to benefit was 100. Per protocol and sensitivity analyses produced similar results. The incidence of adverse reactions was low, with no difference between groups (p = 0.6). Interpretation: There was no significant difference in efficacy between alcoholic and aqueous chlorhexidine for the prevention of surgical site infection after minor skin excisions in general practice. Trial registration: https://www.anzctr.org.au, no. ACTRN1261500104550

The abnormal status of uncarboxylated matrix Gla protein species represents an additional mortality risk in heart failure patients with vascular disease

Background: Matrix Gla protein (MGP) is a natural inhibitor of tissue calcification. In a previous study, we observed the positive association between abnormal concentrations of uncarboxylatedMGP species and increased mortality risk in stable vascular patients. We explore whether co-incidence of abnormal status of uncarboxylated MPG and heart failure (HF) affects the mortality risk. Methods: We examined 799 patients (mean age 65.1 years) with stable vascular disease and followed them in a prospective study. Both, desphospho-uncarboxylated and total uncarboxylated MGP (dp-ucMGP or t-ucMGP) were quantified by pre-commercial ELISA assays. Results: Elevated (>100 ng/L) circulating brain natriuretic peptide (BNP) and abnormal status of plasma uncarboxylated MGP species (i.e.: dp-ucMGP >= 977 pmol/L or t-ucMG

Improving the performance of remote sensing models for capturing intra- and inter-annual variations in daily GPP: An analysis using global FLUXNET tower data

Accurate and reliable estimates of gross primary productivity (GPP) are required for monitoring the globalcarbon cycle at different spatial and temporal scales. Because GPP displays high spatial and temporal vari-ation, remote sensing plays a major role in producing gridded estimates of GPP across spatiotemporalscales. In this context, understanding the strengths and weaknesses of remote sensing-based models ofGPP and improving their performance is a key contemporary scientific activity. We used measurementsfrom 157 research sites (∼470 site-years) in the FLUXNET “La Thuile” data and compared the skills of11 different remote sensing models in capturing intra- and inter-annual variations in daily GPP in sevendifferent biomes. Results show that the models were able to capture significant intra-annual variationin GPP (Index of Agreement = 0.4–0.80) in all biomes. However, the models’ ability to track inter-annualvariation in daily GPP was significantly weaker (IoA < 0.45). We examined whether the inclusion of differ-ent mechanisms that are missing in the models could improve their predictive power. The mechanismsincluded the effect of sub-daily variation in environmental variables on daily GPP, factoring-in differentialrates of GPP conversion efficiency for direct and diffuse incident radiation, lagged effects of environmen-tal variables, better representation of soil-moisture dynamics, and allowing spatial variation in modelparameters. Our analyses suggest that the next generation remote sensing models need better represen-tation of soil-moisture, but other mechanisms that have been found to influence GPP in site-level studiesmay not have significant bearing on model performance at continental and global scales.JRC.E.1-Disaster Risk Managemen