•This ESMO Clinical Practice Guideline provides key recommendations for managing metastatic colorectal cancer.•It covers clinical and pathological diagnosis, staging and risk assessment, treatment ...and follow-up.•Treatment algorithms for locoregional, advanced/metastatic and recurrent advanced colorectal cancer are provided.•All recommendations were compiled by a multidisciplinary group of experts.•Recommendations are based on available scientific data and the authors’ collective expert opinion.
The identification of nitrate (NO3−) sources and biogeochemical transformations is critical for understanding the different nitrogen (N) pathways, and thus, for controlling diffuse pollution in ...groundwater affected by livestock and agricultural activities. This study combines chemical data, including environmental isotopes (δ2HH2O, δ18OH2O, δ15NNO3, and δ18ONO3), with land use/land cover data and a Bayesian isotope mixing model, with the aim of reducing the uncertainty when estimating the contributions of different pollution sources. Sampling was taken from 53 groundwater sites in Comarca Lagunera, northern Mexico, during 2018. The results revealed that the NO3− (as N) concentration ranged from 0.01 to 109 mg/L, with more than 32% of the sites exceeding the safe limit for drinking water quality established by the World Health Organization (10 mg/L). Moreover, according to the groundwater flow path, different biogeochemical transformations were observed throughout the study area: microbial nitrification was dominant in the groundwater recharge areas with elevated NO3− concentrations; in the transition zones a mixing of different transformations, such as nitrification, denitrification, and/or volatilization, were identified, associated to moderate NO3− concentrations; whereas in the discharge area the main process affecting NO3− concentrations was denitrification, resulting in low NO3− concentrations. The results of the MixSIAR isotope mixing model revealed that the application of manure from concentrated animal-feeding operations (∼48%) and urban sewage (∼43%) were the primary contributors of NO3− pollution, whereas synthetic fertilizers (∼5%), soil organic nitrogen (∼4%), and atmospheric deposition played a less important role. Finally, an estimation of an uncertainty index (UI90) of the isotope mixing results indicated that the uncertainties associated with atmospheric deposition and NO3−−fertilizers were the lowest (0.05 and 0.07, respectively), while those associated with manure and sewage were the highest (0.24 and 0.20, respectively).
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•Sources, transformations and contributions of nitrate pollution in groundwater investigated.•Thirty-two percent the samples exceeded the WHO limit for safe drinking water.•Mainly the application of manure and sewage leaks drove the increase of nitrate concentration.•Mixing process among evaporated soil water and recirculated water from irrigation identified.•Different nitrate transformation processes in recharge, transition and discharge areas.
The combined approach estimated a number of nitrate pollution sources and transformation processes in groundwater, whereby manure and sewage leakages were the main drivers.
The first objective of this study was to examine effects of adding Escherichia coli O157:H7 with or without chemical or microbial additives on the bacterial diversity and composition of alfalfa ...silage. The second objective was to examine associations between the relative abundance of known and unknown bacterial species and indices of silage fermentation quality. Alfalfa forage was harvested at 54% dry matter, chopped to a theoretical length of cut of 19 mm, and ensiled in quadruplicate in laboratory silos for 100 d after the following treatments were applied: (1) distilled water (control); (2) 1 × 105 cfu/g of E. coli O157:H7 (EC); (3) EC and 1 × 106 cfu/g of Lactobacillus plantarum (EC+LP); (4) EC and 1 × 106 cfu/g of Lactobacillus buchneri (EC+LB); and (5) EC and 0.22% propionic acid (EC+PA). After 100 d of ensiling, the silage samples were analyzed for bacterial diversity and composition via the Illumina MiSeq platform (Illumina Inc., San Diego, CA) and chemically characterized. Overall, Firmicutes (74.1 ± 4.86%) was the most predominant phylum followed by Proteobacteria (20.4 ± 3.80%). Relative to the control, adding E. coli O157:H7 alone at ensiling did not affect bacterial diversity or composition but adding EC+LP or EC+LB reduced the Shannon index, a measure of diversity (3.21 vs. 2.63 or 2.80, respectively). The relative abundance of Firmicutes (69.2 and 68.8%) was reduced, whereas that of Proteobacteria (24.0 and 24.9%) was increased by EC+LP and EC+PA treatments, relative to those of the control (79.5 and 16.5%) and EC+LB (77.4 and 18.5%) silages, respectively. Compared with the control, treatment with EC+LP increased the relative abundance of Lactobacillus, Sphingomonas, Pantoea, Pseudomonas, and Erwinia by 426, 157, 200, 194, and 163%, respectively, but reduced those of Pediococcus, Weissella, and Methylobacterium by 5,436, 763, and 250%, respectively. Relative abundance of Weissella (9.19%) and Methylobacterium (0.94%) were also reduced in the EC+LB silage compared with the control (29.7 and 1.50%, respectively). Application of propionic acid did not affect the relative abundance of Lactobacillus, Weissella, or Pediococcus. Lactate concentration correlated positively (r = 0.56) with relative abundance of Lactobacillus and negatively (r = −0.41) with relative abundance of Pediococcus. Negative correlations were detected between ammonia-N concentration and relative abundance of Sphingomonas (r = −0.51), Pantoea (r = −0.46), Pseudomonas (r = −0.45), and Stenotrophomonas (r = −0.38). Silage pH was negatively correlated with relative abundance of Lactobacillus (r = −0.59), Sphingomonas (r = −0.66), Pantoea (r = −0.69), Pseudomonas (r = −0.69), and Stenotrophomonas (r = −0.50). Future studies should aim to speciate, culture, and determine the functions of the unknown bacteria detected in this study to elucidate their roles in silage fermentation.