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"Light cannabis" is a product legally sold in Europe with Δ9-tetrahydrocannabinol (THC) concentration <0.2% and variable cannabidiol (CBD) content. In this study, we aimed to assess the time courses of THC and metabolites (11-nor-9-carboxy-THC and 11-hydroxy-THC) and CBD and metabolites (CBD-7-oic acid, 7-hydroxy-CBD, 6α-hydroxy-CBD and 6β-hydroxy-CBD) in whole blood of 10 healthy participants after smoking one or four light cannabis cigarettes (0.16% THC and 5.8% CBD). Blood samples were collected 0.5–4 h after administration. Blood analysis was performed by reversed-phase ultra-performance liquid chromatography–tandem mass spectrometry in multiple reaction monitoring mode after glucuronide hydrolysis and liquid–liquid extraction in basic and acidic conditions. The method was validated following the most recent guidelines in toxicology: the method was linear, accurate, precise and sensitive (lower limits of quantification ranged from 0.005 to 0.01 ng/mL); carryover, matrix effect, recovery, process efficiency and dilution integrity were also assessed. As previously reported, the main metabolites of THC were THC-COOH and then 11-OH-THC, and the main metabolites of CBD were 7-OH-CBD and then 7-COOH-CBD. The time of the first collection, which likely occurred after the maximal concentration of most of the analytes, and the short monitoring time, up to 4 h after smoking, limited the evaluation of the pharmacokinetic parameters. [ABSTRACT FROM AUTHOR]

Over the last decades, treatment of domestic wastewater promoted by environmental regulations have reduced human health risks and improved water quality. However, ecological risks caused by effluents of wastewater treatment plants (WWTPs) discharged into rivers still persist. Moreover, the evolution of these ecological risks in the future is intimately related to effects of changing climate, especially regarding streamflow in receiving rivers. Here, we present an analytical and transferable framework for assessing the ecological risks posed by WWTP‐effluents at the catchment scale. The framework combines the size‐class k of WWTPs, which is a load‐proxy, with their outflows' location in river networks, represented by stream‐order ω. We identify ecological risks by using three proxy indicators: the urban discharge fraction and the local‐scale concentrations of each total phosphorous and ammonium‐nitrogen discharged from WWTPs. About 3,200 WWTPs over three large catchments (Rhine, Elbe, and Weser) in Central Europe were analyzed by incorporating simulated streamflow for the most extreme projected climate change scenario. We found that WWTPs causing ecological risks in the future prevail in lower ω, across almost all k. Distinct patterns of ecological risks are identified in the k‐ω framework for different indicators and catchments. We show, as climate changes, intensified risks are especially expected in lower ω receiving effluents of intermediate‐k WWTPs. We discuss the implications of our findings for prioritizing WWTPs upgrading and urging updates on environmental regulations. Further discussions underline the feasibility of applying the framework to any geographical regions and highlight its potentials to help in achieving global long‐term commitments on freshwater security. Key Points: An analytical, generic framework was developed to assess wastewater treatment plants causing ecological risks in rivers under climate changeSmaller streams will face higher ecological risks for almost all load classes of wastewater treatment plants in future climateOf the legally regulated effluent parameters for treated wastewater, ammonium‐nitrogen concentration will pose the greatest ecological risk [ABSTRACT FROM AUTHOR]

Complex mixtures of micropollutants, including pesticides, pharmaceuticals and industrial chemicals emitted by wastewater effluents to European rivers may compromise the quality of these water resources and may pose a risk to ecosystem health and abstraction of drinking water. In the present study, an integrated analytical and bioanalytical approach was applied to investigate the impact of untreated wastewater effluents from the city of Novi Sad, Serbia, into the River Danube. The study was based on three on-site large volume solid phase extracted water samples collected upstream and downstream of the untreated wastewater discharge. Chemical screening with liquid chromatography high resolution mass spectrometry (LC-HRMS) was applied together with a battery of in vitro cell-based bioassays covering important steps of the cellular toxicity pathway to evaluate effects on the activation of metabolism (arylhydrocarbon receptor AhR, peroxisome proliferator activated receptor gamma PPARγ), specific modes of action (estrogen receptor ERα, androgen receptor AR) and adaptive stress responses (oxidative stress, inflammation). Increased effects, significantly changed contamination patterns and higher chemical concentrations were observed downstream of the wastewater discharge. A mass balance approach showed that enhanced endocrine disruption was in good agreement with concentrations of detected hormones, while only a smaller fraction of the effects on xenobiotic metabolism (<1%) and adaptive stress responses (0–12%) could be explained by the detected chemicals. The chemical and effects patterns observed upstream of the discharge point were fairly re-established at about 7 km downstream, demonstrating the enormous dilution capacity of this large river. [ABSTRACT FROM AUTHOR]

Polycyclic aromatic hydrocarbons (PAHs) were included as priority substances for human biomonitoring (HBM) in the European Human Biomonitoring Initiative (HBM4EU), which intended to harmonise and advance HBM across Europe. For this project, a specific Quality Assurance and Quality Control (QA/QC) programme applying Inter-laboratory Comparison Investigations (ICIs) and External Quality Assurance Schemes (EQUASs) was developed to ensure the comparability and accuracy of participating analytical laboratories. This paper presents the results of four ICI/EQUAS rounds for the determination of 13 PAH metabolites in urine, i.e. 1-naphthol, 2-naphthol, 1,2-dihydroxynaphthalene, 2-, 3- and 9-hydroxyfluorene, 1-, 2-, 3-, 4- and 9-hydroxyphenanthrene, 1-hydroxypyrene and 3-hydroxybenzo(a)pyrene. However, 4 PAH metabolites could not be evaluated as the analytical capacity of participating laboratories was too low. Across all rounds and biomarkers, 86% of the participants achieved satisfactory results, although low limits of quantification were required to quantify the urinary metabolites at exposure levels of the general population. Using high-performance liquid or gas chromatography coupled with mass spectrometry (HPLC-MS; GC-MS) and isotope dilution for calibration as well as performing an enzymatic deconjugation step proved to be favourable for the accurate determination of PAHs in urine. Finally, the HBM4EU QA/QC programme identified an international network of laboratories providing comparable results in the analysis of urinary PAH biomarkers, although covering all parameters initially selected was still too challenging. [Display omitted] [ABSTRACT FROM AUTHOR]

In Europe the maximum allowable concentration for tributyltin (TBT) compounds in surface water has been regulated by the water framework directive (WFD) and daughter directive that impose a limit of 0.2 ng L −1 in whole water (as tributyltin cation). Despite the large number of different methodologies for the quantification of organotin species developed in the last two decades, standardised analytical methods at required concentration level do not exist. TBT quantification at picogram level requires efficient and accurate sample preparation and preconcentration, and maximum care to avoid blank contamination. To meet the WFD requirement, a method for the quantification of TBT in mineral water at environmental quality standard (EQS) level, based on solid phase extraction (SPE), was developed and optimised. The quantification was done using species-specific isotope dilution (SSID) followed by gas chromatography (GC) coupled to inductively coupled plasma mass spectrometry (ICP–MS). The analytical process was optimised using a design of experiment (DOE) based on a factorial fractionary plan. The DOE allowed to evaluate 3 qualitative factors (type of stationary phase and eluent, phase mass and eluent volume, pH and analyte ethylation procedure) for a total of 13 levels studied, and a sample volume in the range of 250–1000 mL. Four different models fitting the results were defined and evaluated with statistic tools: one of them was selected and optimised to find the best procedural conditions. C18 phase was found to be the best stationary phase for SPE experiments. The 4 solvents tested with C18, the pH and ethylation conditions, the mass of the phases, the volume of the eluents and the sample volume can all be optimal, but depending on their respective combination. For that reason, the equation of the model conceived in this work is a useful decisional tool for the planning of experiments, because it can be applied to predict the TBT mass fraction recovery when the experimental conditions are drawn. This work shows that SPE is a convenient technique for TBT pre-concentration at pico-trace levels and a robust approach: in fact (i) number of different experimental conditions led to satisfactory results and (ii) the participation of two institutes to the experimental work did not impact the developed model. [ABSTRACT FROM AUTHOR]

Abstract: Broth microdilution and macrodilution assays were used to determine minimum inhibitory concentrations (MICs) and minimum bactericidal concentrations (MBCs) of six antimicrobial agents (ceftriaxone, cefuroxime sodium, azithromycin, amoxicillin, doxycycline and amikacin) for nine European human isolates of Borrelia burgdorferi sensu stricto (s.s.). Strains were obtained from patients diagnosed with Lyme borreliosis in Slovenia. Modified Kelly–Pettenkofer medium with a final inoculum of 105 Borrelia cells/mL and incubation periods of 72h and of 3 weeks and 6 weeks were used in the determination of MICs and MBCs, respectively. Observed MICs indicated that all isolates were susceptible to all the tested antimicrobial agents with the exception of amikacin. Cefuroxime sodium (MIC90 =0.063mg/L), azithromycin (MIC90 =0.22mg/L) and ceftriaxone (MIC90 =0.25mg/L) displayed the lowest MICs, followed by amoxicillin (MIC90 =1mg/L) and doxycycline (MIC90 =2mg/L); no strain was susceptible to amikacin (MIC90 =256mg/L). MBCs after incubation for 3 weeks and 6 weeks were determined for amoxicillin (MBC90 =32mg/L), doxycycline (MBC90 =32mg/L) and amikacin (MBC90 =1024mg/L) and were found to be high (but not defined) for azithromycin (MBC90 >0.88mg/L), cefuroxime sodium (MBC90 >4mg/L) and ceftriaxone (MBC90 >4mg/L). In determination of borrelial susceptibility to antimicrobial agents, intrinsic low susceptibility or methodological factors could result in low in vitro susceptibility of individual strains. This study is the first report on the antibiotic susceptibility of a series of European human isolates of B. burgdorferi s.s. [Copyright &y& Elsevier]

This paper critically examines the discourse surrounding fair trade mainstreaming, and discusses the potential avenues for the future of the social movement. The authors have a unique insight into the fair trade market having a combined experience of over 30 years in practice and 15 as fair trade scholars. The paper highlights a number of benefits of mainstreaming, not least the continued growth of the global fair trade market (tipped to top $7bn in 2012). However, the paper also highlights the negative consequences of mainstreaming on the long-term viability of fair trade as a credible ethical standard. [ABSTRACT FROM AUTHOR]

The Etest manufacturer (bioMerieux) recommends Mueller–Hinton agar (MHA) with calcium concentration of 25–40 mg/L for daptomycin testing. A two phase study was performed to evaluate the effect of European agars on daptomycin Etest MICs. Broth microdilution (BMD) testing was performed and compared to Etest MICs for a challenge set of 20 Staphylococcus aureus with daptomycin MICs near the susceptible breakpoint and S. aureus 29213. In the first phase, Etest MICs were determined using agar plates prepared from MHA, IsoSensitest Agar (ISA) and Brain-Heart Infusion Agar (BHIA) and supplemented with various levels of calcium. In the second phase, Etest MICs were determined using commercially prepared MHA from Mast (MST), BD, Oxoid (OX), BioRad (BR), bioMerieux (BM) and E&O (EO) and ISA plates from OX, EO and MST. The calcium concentration of each agar was determined using ion selective electrode methodology. The best correlation of Etest and BMD MICs was obtained in phase 1 using MHA with 42.8 mg/L calcium and in phase 2 with BD MHA. The phase 2 MHA calcium concentration ranged from 19.2 to 63.6 mg/L. 87.5% of strains with BMD MICs of 1 mg/L, had Etest MICs of 1.5 or 2 mg/L using MHA with recommended calcium levels. Etest MICs using BHIA and ISA were higher than the BMD MICs and therefore are not recommended for use with the daptomycin Etest. The high percentage of major errors using Etest in this study, even with use of the most optimal medium, suggests that Etest MICs of 1.5 or 2 mg/L using MHA should be retested by BMD. [ABSTRACT FROM AUTHOR]

To improve the accuracy, reliability, and representativeness of emission factors, 10 European laboratories worked together to study the influence of 20 parameters on the measurement of light-vehicle emission factors on chassis dynamometer of 4 main categories: driving patterns, vehicle-related parameters, vehicle sampling, and laboratory-related parameters. The results are based on (1) literature synthesis, (2) approximately 2700 specific tests with 183 vehicles, and (3) the reprocessing of more than 900 tests. These tests concern the regulated atmospheric pollutants and pre-Euro to Euro 4 vehicles. Of the 20 parameters analyzed, 7 seemed to have no effect, 7 were qualitatively influential, and 6 were highly influential (gearshift strategy, vehicle mileage, ambient temperature, humidity, dilution ratio, and driving cycle). The first four of the six were able to have correction factors developed for them. The results allow for the design of recommendations or guidelines for the emission factor measurement method. [ABSTRACT FROM AUTHOR]

Background: Gastrointestinal cancer antigen CA19-9 is known as a valuable marker for the management of patients with pancreatic cancer. Methods: The analytical and clinical performance of the Access® GI Monitor assay (Beckman Coulter) was evaluated on the UniCel® DxI 800 Immunoassay System at five different European sites and compared with a reference method, defined as CA19-9 on the Elecsys System (Roche Diagnostics). Results: Total imprecision (%CV) of the GI Monitor ranged between 3.4% and 7.7%, and inter-laboratory reproducibility between 3.6% and 4.0%. Linearity upon dilution showed a mean recovery of 97.4% (SD+7.2%). Endogenous interferents had no influence on GI Monitor levels (mean recoveries: hemoglobin 103%, bilirubin 106%, triglycerides 106%). There was no high-dose hook effect up to 115,000 kU/L. Clinical performance investigated in sera from 1811 individuals showed a good correlation between the Access® GI Monitor and Elecsys CA19-9 (R=0.959, slope=1.004, intercept=+0.17). GI Monitor serum levels were low in healthy individuals (n=267, median=6.0 kU/L, 95th percentile=23.1 kU/L), higher in individuals with various benign diseases (n=550, medians=5.8–13.4 kU/L, 95th percentiles=30.1–195.5kU/L) and even higher in individuals suffering from various cancers (n=995, medians=8.4–233.8 kU/L, 95th percentiles=53.7–13,902 kU/L). Optimal diagnostic accuracy for cancer detection against the relevant benign control group by the GI Monitor was found for pancreatic cancer [area under the curve (AUC) 0.83]. Results for the reference CA19-9 assay were comparable (AUC 0.85). Conclusions: The Access® GI Monitor provides very good methodological characteristics and demonstrates an excellent analytical and clinical correlation with the Elecsys CA19-9. The GI Monitor shows the best diagnostic accuracy in pancreatic cancer. Our results also suggest a clinical value of the GI Monitor in other cancers. Clin Chem Lab Med 2008;46:600–11. [ABSTRACT FROM AUTHOR]

One of the most controversial topics concerning Neisseria meningitidis is the definition of antimicrobial resistance. A process of harmonization, promoted by the European Monitoring Group on Meningococci (EMGM), is already in progress. There are several aspects of the MIC definition for meningococcal strains for which a consensus is needed, as follows. (1) What methods can be used? At present, both the Etest and agar dilution methods are recommended by the EMGM. Microdilution, also a recommended method, is not used across Europe. (2) What media produce the most reliable data? The use of Mueller–Hinton medium supplemented with 5% blood is recommended for the MIC determination of N. meningitidis by both Etest and agar dilution method. (3) What is the minimum set of antimicrobial agents to be tested? A minimum set should include rifampicin, ciprofloxacin (or another quinolone), penicillin, ampicillin and ceftriaxone. (4) What are the most suitable breakpoints for definition? There is no widely accepted robust evidence base for the definition of breakpoints. Although progress has been made in achieving a standardized methodology, we are still far from obtaining common breakpoints for antimicrobial resistance definition. These differences will imply inability for building a common epidemiologic figure about drug resistance. [ABSTRACT FROM AUTHOR]

Abstract: Under the EU Directive 2004/28/EC, an environmental risk assessment of new veterinary medicinal products is required. Given the nature of risk assessment for new applications, there is a need to model exposure concentrations. Critical evaluations are essential to ensure that the use of models by regulators does not result in the propagation of misleading information. The empirical validations of soil exposure models, previously discussed in this journal, indicate that it is impossible to analyse the contribution of every model parameter to the variability in the predictions. In particular, the prediction of the slurry concentration is challenged by uncertainties concerning dilution, mixing and dissipation of residues. Surface water and groundwater models generated highly deviating results compared to the field results, questioning the usefulness of the available screening models. Animal husbandry, slurry handling and environmental conditions throughout Europe are considered in order to define realistic worst case scenarios, to be used in conjunction with distribution models for the environmental risk assessment of veterinary medicinal products at registration. Given the variability in manure management practice throughout Europe, a deterministic approach for the manure-to-soil model was selected. Both worst case and best case scenario were developed. Several modelling assumptions applied in the surface water exposure model for fish nursery effluent were validated against newly available data. Since the available data give no proof that a settling tank contributes to the removal of pesticides from waste water, it is recommended for risk assessment purposes to consider the contribution of the settling tank to removal of pesticides and medicines to be negligible. Surface water dilution factors may be considered to be rather small, a factor of 2, for low flow situations. [Copyright &y& Elsevier]

• EU Rivers' capacity to dilute wastewater treatment plants discharges is assessed • Climate change will lead to a dilution factor decrease for 11% of the EU rivers • 42% of the rivers will downgrade their ecological status due to climate change • More vulnerable sites are located in the Mediterranean countries Impacts from urban wastewater treatment plants (WWTP) to receiving riverine surface water bodies (SWBs) depend on the load of contaminants discharged, as well as on their dilution capacity. Yet, climate change impacts on such dilution capacity and ultimately on the SWBs ecological status remain unclear. Here, we assess SWBs dilution capacity across the European continent to identify most vulnerable areas using information from centralized European databases. SWBs´ future dilution factor values are estimated based on representative concentration pathway scenarios impacts on rivers flow, and likely changes in European SWBs´ ecological status foretold. Results show that dilution factor in Europe increases by 5.4% in average. Yet, climate change effects are found to lead to a consistent dilution factor decrease for 11% of the 40074 European SWBs receiving WWTP discharge for the early century. This share reaches 17% for the midcentury period. We estimate that up to 42% of the SWBs receiving WWTP discharges and currently reaching a good ecological status show a 0.7 probability to have their ecological status downgraded due to climate change. Sites more vulnerable are located in the Mediterranean countries. Our findings highlight that climate change mitigation is essential for maintaining good ecological status in European SWBs. [Display omitted] [ABSTRACT FROM AUTHOR]

Reducing the number of spermatozoa per artificial insemination (AI) dose and managing semen in ways to ensure greater quality at the same time represents current challenges with sperm processing in pig AI centers. Based on a multi-year comparative analysis of process steps in different pig AI centers, and complementary experimental studies under standardized laboratory conditions, current process standards for the preservation of boar semen have been updated and new ones developed. Currently, these standards represent an integral part of the quality assurance of 29 European pig AI centers in ten different organizations in Germany, Switzerland and Austria. Improvement of hygiene management and guidelines for prudent use of antibiotics have become key issues. Furthermore, new quality control tools have been implemented in the processing and transport of boar semen: e.g. refractometry as an easy-to-use tool to estimate extender osmolarity and 'mobile sensing' apps for continuous monitoring of various environmental parameters. Moreover, based on a series of experiments under laboratory and field conditions, guidelines for optimizing the dilution process, and time and temperature management during boar semen processing, have been developed and implemented. Similarly, recommendations for the handling of semen doses during storage have been renewed. Over the years, the efficiency of the quality assurance system has been reflected by a decrease of bacterial contamination and a concomitant increase in the quality of semen doses. In conclusion, science-based quality assurance is an effective way to improve the production performance in pig AI centers, resulting in high quality and economically-priced semen for pig producers. Increasing knowledge of sperm physiology together with computational and technical innovations will continue to develop and modify quality assurance concepts in the future., (Copyright © 2019 Elsevier Inc. All rights reserved.)

The article focuses on the European court case IPC Media Ltd. v. Media 10 Ltd., which dealt with the concurrent use of retail trademarks. Topics include the interpretation of European Union (EU) trademark law by the Intellectual Property and Enterprise Court, trademark confusion, and the establishment of double identities in trademark law.