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Background and Objective: There is no consensus on the optimal vancomycin dose to achieve pharmacokinetic/pharmacodynamic (PK/PD) target in patients with hematologic cancer or in hematopoietic stem cell transplant (HSCT) recipients. A 24-h area under the concentration-time curve (AUC) >400 mg*h/L must be achieved early for successful treatment of severe methicillin-resistant Staphylococcus aureus (MRSA) infections. Current nomograms derived from general population data are not sufficiently accurate to allow AUC-based model-informed precision dosing. The objective of this study was to characterize vancomycin PK in patients with hematologic cancer or in HSCT recipients and to develop a model-informed dosing tool based on PK/PD target requirements., Methods: Pooled retrospective and prospective vancomycin serum concentrations were analyzed using NONMEM ® to evaluate the performance of previously published population PK (popPK) models built from hematologic cancer datasets and to develop a novel Bayesian PK model. Patients' characteristics and clinical data were tested as potential covariates. The popPK model was validated internally and externally. Predictions of vancomycin concentrations for different dosing regimens were made using Monte-Carlo simulations, and a nomogram strategy was proposed according to selected probability of target attainment (PTA)., Results: The predictive performance of the published popPK models was found to be suboptimal for our population. A novel popPK model was developed using 240 vancomycin concentrations (60 patients). A two-compartment structural model with an additive error model best described the data. Ideal body weight and estimated glomerular filtration rate (eGFR) [Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI)] were selected as covariates for volume of distribution (V) and clearance (CL). Bootstrapping confirmed the stability and precision of the popPK parameters. The volume of distribution was V1 = 46.8 L and V2 = 56.1 L, while CL = 5.63 L/h. External validation using 107 vancomycin concentrations (24 patients) demonstrated the predictivity of the model. A nomogram was developed to reach minimally PTA >50% for 400 < AUC < 600 mg*h/L., Conclusion: To our knowledge, this study provides the first model-informed AUC-based strategy in North American hematologic cancer patients with or without HSCT. The resulting nomogram generated provides a simplified approach to improving the accuracy of initial vancomycin dosing in this population., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Anthropogenic activities profoundly impact soil organic carbon (SOC), affecting its contribution to ecosystem services such as climate regulation. Here, we conducted a thorough review of the impacts of land-use change, land management, and climate change on SOC. Using second-order meta-analysis, we synthesized findings from 230 first-order meta-analyses comprising over 25,000 primary studies. We show that (i) land conversion for crop production leads to high SOC loss, that can be partially restored through land management practices, particularly by introducing trees and incorporating exogenous carbon in the form of biochar or organic amendments, (ii) land management practices that are implemented in forests generally result in depletion of SOC, and (iii) indirect effects of climate change, such as through wildfires, have a greater impact on SOC than direct climate change effects (e.g., from rising temperatures). The findings of our study provide strong evidence to assist decision-makers in safeguarding SOC stocks and promoting land management practices for SOC restoration. Furthermore, they serve as a crucial research roadmap, identifying areas that require attention to fill the knowledge gaps concerning the factors driving changes in SOC., (© 2023. The Author(s).)

Increasing soil organic carbon (SOC) in natural and cultivated ecosystems is proposed as a natural climate solution to limit global warming. SOC dynamics is driven by numerous factors such as  land-use change, land management and climate change. The amount of additional carbon potentially stored in the soil is the subject of much debate in the scientific community. We present a global database compiling the results of 217 meta-analyses analyzing the effects of land management, land-use change and climate change on SOC. We report a total of 15,857 effect sizes, 6,550 directly related to soil carbon, and 9,307 related to other associated soil or plant variables. The database further synthesizes results of 13,632 unique primary studies across more than 150 countries that were used in the meta-analyses. Meta-analyses and their effect sizes and were classified by type of intervention and land use, outcomes, country and region. This database helps to understand the drivers of SOC sequestration, the associated co-benefits and potential drawbacks, and is a useful tool to guide future global climate change policies., (© 2022. The Author(s).)

Major drivers of gains or losses in soil organic carbon (SOC) include land management, land-use change, and climate change. Thousands of original studies have focused on these drivers of SOC change and are now compiled in a growing number of meta-analyses. To critically assess the research efforts in this domain, we retrieved and characterized 192 meta-analyses of SOC stocks or concentrations. These meta-analyses comprise more than 13,200 original studies conducted from 1910 to 2020 in 150 countries. First, we show that, despite a growing number of studies over time, the geographical coverage of studies is limited. For example, the effect of land management, land-use change, and climate change on SOC has been only occasionally studied in North and Central Africa, and in the Middle East and Central Asia. Second, the meta-analyses investigated a limited number of land management practices, mostly mineral fertilization, organic amendments, and tillage. Third, the meta-analyses demonstrated relatively low quality and transparency. Lastly, we discuss the mismatch between the increasing number of studies and the need for more local, reusable, and diversified knowledge on how to preserve high SOC stocks or restore depleted SOC stocks., (© 2021 John Wiley & Sons Ltd.)

A new membrane-associated 2,4,6-trichlorophenol reductive dehalogenase from Desulfitobacterium frappieri PCP-1 was isolated. Initial characterization of the crude preparation showed that the dechlorinating activity was sensitive to oxygen, and its optimum pH was 7.0. Its dechlorinating activity was not inhibited by sulphate, was completely inhibited by 1 mM sulphite, and partially inhibited by 5 mM sodium azide and by more than 5 mM nitrate. Several polychlorophenols were dechlorinated in the ortho position with respect to the hydroxy group. A dehalogenase was purified to apparent homogeneity. SDS gel electrophoresis revealed a single protein band with a molecular mass of 37 kDa. However, after two-dimensional gel electrophoresis, this band was composed of three isoforms. MS analyses showed that the three isoforms were from the same protein and the molecular mass of the most abundant isoform is 33800 Da. A mixture of iodopropane and titanium citrate caused a light-reversible inhibition of the dechlorinating activity, suggesting the involvement of a corrinoid cofactor. The apparent K(m) value for 2,4,6-trichlorophenol and pentachlorophenol were 18.3+/-2.8 microM and 26.8+/-2.9 microM respectively, at a methyl viologen concentration of 2 mM. The N-terminal amino acid sequence and an internal tryptic peptide sequence were determined. One open reading frame (ORF) was found in the Desulfitobacterium hafniense genome containing these peptides sequences. The corresponding ORF in D. frappieri PCP-1 was cloned and sequenced. This ORF, that we designated crdA, showed no homology with any known dehalogenase, suggesting a distinct reductive dehalogenase.