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Background
Quantitative measurements of cerebrospinal fluid to blood clearance has previously not been established for neurological diseases. Possibly, variability in cerebrospinal fluid clearance may affect the underlying disease process and may possibly be a source of under- or over-dosage of intrathecally administered drugs. The aim of this study was to characterize the cerebrospinal fluid to blood clearance of the intrathecally administered magnetic resonance imaging contrast agent gadobutrol (Gadovist, Bayer Pharma AG, GE). For this, we established a population pharmacokinetic model, hypothesizing that cerebrospinal fluid to blood clearance differs between cerebrospinal fluid diseases.
Methods
Gadobutrol served as a surrogate tracer for extra-vascular pathways taken by several brain metabolites and drugs in cerebrospinal fluid. We estimated cerebrospinal fluid to blood clearance in patients with different cerebrospinal fluid disorders, i.e. symptomatic pineal and arachnoid cysts, as well as tentative spontaneous intracranial hypotension due to cerebrospinal fluid leakage, idiopathic intracranial hypertension, or different types of hydrocephalus (idiopathic normal pressure hydrocephalus, communicating- and non-communicating hydrocephalus). Individuals with no verified cerebrospinal fluid disturbance at clinical work-up were denoted references.
Results
Population pharmacokinetic modelling based on 1,140 blood samples from 161 individuals revealed marked inter-individual variability in pharmacokinetic profiles, including differences in absorption half-life (time to 50% of tracer absorbed from cerebrospinal fluid to blood), time to maximum concentration in blood and the maximum concentration in blood as well as the area under the plasma concentration time curve from zero to infinity. In addition, the different disease categories of cerebrospinal fluid diseases demonstrated different profiles.
Conclusions
The present observations of considerable variation in cerebrospinal fluid to blood clearance between individuals in general and across neurological diseases, may suggest that defining cerebrospinal fluid to blood clearance can become a useful diagnostic adjunct for work-up of cerebrospinal fluid disorders. We also suggest that it may become useful for assessing clearance capacity of endogenous brain metabolites from cerebrospinal fluid, as well as measuring individual cerebrospinal fluid to blood clearance of intrathecal drugs.
2022
Organic aerosol (OA) is a key component of total submicron particulate matter (PM1), and comprehensive knowledge of OA sources across Europe is crucial to mitigate PM1 levels. Europe has a well-established air quality research infrastructure from which yearlong datasets using 21 aerosol chemical speciation monitors (ACSMs) and 1 aerosol mass spectrometer (AMS) were gathered during 2013–2019. It includes 9 non-urban and 13 urban sites. This study developed a state-of-the-art source apportionment protocol to analyse long-term OA mass spectrum data by applying the most advanced source apportionment strategies (i.e., rolling PMF, ME-2, and bootstrap). This harmonised protocol was followed strictly for all 22 datasets, making the source apportionment results more comparable. In addition, it enables quantification of the most common OA components such as hydrocarbon-like OA (HOA), biomass burning OA (BBOA), cooking-like OA (COA), more oxidised-oxygenated OA (MO-OOA), and less oxidised-oxygenated OA (LO-OOA). Other components such as coal combustion OA (CCOA), solid fuel OA (SFOA: mainly mixture of coal and peat combustion), cigarette smoke OA (CSOA), sea salt (mostly inorganic but part of the OA mass spectrum), coffee OA, and ship industry OA could also be separated at a few specific sites. Oxygenated OA (OOA) components make up most of the submicron OA mass (average = 71.1%, range from 43.7 to 100%). Solid fuel combustion-related OA components (i.e., BBOA, CCOA, and SFOA) are still considerable with in total 16.0% yearly contribution to the OA, yet mainly during winter months (21.4%). Overall, this comprehensive protocol works effectively across all sites governed by different sources and generates robust and consistent source apportionment results. Our work presents a comprehensive overview of OA sources in Europe with a unique combination of high time resolution (30–240 min) and long-term data coverage (9–36 months), providing essential information to improve/validate air quality, health impact, and climate models.
2022
Integrated assessment of noise and air quality in European cities. Methodology.
The resulting index provides spatial information on the areas most affected combining noise and air pollution across European urban areas. This information can build on and contribute to the EEA’s integrated assessments and it is going to be used to disseminate information on the European environment to policy makers and to European citizens.
ETC/ATNI
2022
Grenseområdene Norge-Russland. Luft- og nedbørkvalitet 2021.
Smelteverkene i nordvest-Russland slapp tidligere ut store mengder svoveldioksid (SO2) og tungmetaller. Utslippene påvirket luft- og nedbørkvalitet i grenseområdene. Smelteverket i Nikel stengte ned 23. desember 2020 og lokal luftkvalitet ble betydelig forbedret. Dog er det fortsatt utslipp fra varmekraftverket i Nikel i den kalde årstiden. Detaljer rundt utslippene fra Zapoljarnyj er ikke kjente. Herværende rapport viser resultatene for kalenderåret 2021, det vil si året etter stengningen. Nivåene av forurensning er lave og grenseverdier og målsettingsverdier er overholdt med klar margin.
NILU
2022
Condensable primary organic aerosol (CPOA) emissions are a class of organic compounds that are vapour phase at stack conditions, but which can undergo both condensation and evaporation processes as the stack air is cooled and diluted upon discharge into ambient air. Emission factors may misrepresent, and even miss, the amount of particulate matter (PM) or gas that actually enters the atmosphere, depending on the emission measurement techniques used. In the current emission reporting to EMEP/CLRTAP there is no clear definition of whether condensable organics are included or not, and, if included, to what extent.
In this study, new residential combustion emission estimates have been made for the years 2005-2019 (called TNO Ref2_v2.1) in a consistent manner, with improved estimation of fuel consumption (in particular wood) and emission factors, as well as an updated split of fuel use over different appliances and technologies. For these two elements, data were taken primarily from the Eurostat fuel statistics and the IIASA GAINS model. Three scenarios have been defined: a “typical” case, which is our best estimate, an alternative “ideal” case which excludes the impact of “bad combustion”, and a “high EF” scenario in which higher emission factors are assumed than in the typical scenario. Total emissions in the typical scenario are around 40% higher than in the ideal case (in 2019), whereas resulting emissions in the “high EF” scenario are around 90% higher than in the typical scenario.
The Ref2_v2.1 inventory was used in a series of modelling studies which aimed to assess the importance of condensable organics for current air quality, for trends over time (2010–2019), and for source-receptor calculations.
Including condensables in a consistent way for all countries gave model results (concentrations, trends and bias) in better agreement with observations for OC and PM2.5 than when using the EMEP emissions which have condensables for some countries but not others. However, the model results were sensitive to the choice of Ref2_v2.1 scenario, and also to the assumptions concerning volatility of the CPOA emissions, and assumptions about extra intermediate-volatility volatile organic compounds (IVOC) associated with such emissions.
No single setup performed best for each site. There are many factors that can contribute to such mixed results (activity data, emissions factors, assumed combustion conditions, large and small scale spatial distributions issues in emissions, dispersion and CPOA/IVOC assumptions in the modelling), and much further work (and with other observational data-sets) will be needed to disentangle the reasons for model-measurement discrepancies, and to draw conclusions on how realistic the new emissions are.
Assumptions about volatility seem to be important for both the country-to-itself contribution, and for impacts of each country on others. In the few cases investigated so far, assuming inert CPOA provides results which generally lie within the range of the more complex VBS scenarios. Given the many uncertainties associated with the emissions and the modelling of POA and SOA, these results indicates that the inert CPOA assumptions provide a reasonable first approach for handling POA emissions, which can hopefully be improved once our understanding of the sources and processing of these compounds improves.
The new emission data-base, combined with increasing availability of measurements of organic and other components, should provide the best available basis for future improvements in both the emission inventories and model formulations. Much analysis and further tests remain, both with the other model setups, and ideally with alternative secondary organic aerosol schemes to get a better idea of the sensitivity of the results to the various assumptions concerning both emissions and atmospheric processing of POA.
Nordic Council of Ministers
2022
Revidert tiltaksutredning for lokal luftkvalitet i Bergen
Tiltaksutredningen for lokal luftkvalitet i Bergen med handlings- og beredskapsplan skal bidra til at forurensningsnivået holder seg innenfor kravene i forurensningsforskriften. Tiltaksutredningen omfatter en kartlegging av luftkvaliteten i Bergen kommune ved trafikkberegninger og utslipps- og spredningsberegninger for PM10, PM2,5 og NO 2 for Dagens situasjon 2019 og Referansesituasjonen 2030 med eksisterende og eventuelle nye tiltak. Utredningen vurderer effekten som tiltakene har for å overholde krav, men ser også på muligheten for ytterligere reduksjon i henhold til anbefalingene til helsemyndighetene. Basert på resultatene fra beregningene og i samarbeid med oppdragsgiver og referansegruppen, er det foreslått en revidert handlings- og beredskapsplan som skal behandles politisk.
NILU
2022
The aim of this project was to collect, integrate and analyse observations of climate-relevant aerosol parameters (aerosol optical depth (AOD), Ångstrøm exponent (AE), black carbon (BC)) in and around Svalbard. These observations have been performed at different places and with different instrument types, the analysis procedures of which follow different protocols. Annual merged datasets of AOD, AE and BC have been provided to the SIOS Data Management System and are now available for network-wide use in, e.g., Arctic climate and pollution studies. The analysis of the 2002-2020 data have confirmed earlier results showing a good correlation between measurements in Ny-Ålesund and Hornsund, but not a high degree of short-term agreement due to aerosol variability arising from geographical locations and local conditions. There is also a clear link between the columnar AOD/AE-measurements and in-situ aerosol measurements at Gruvebadet Observatory, while a comparison of in-situ measurements at Gruvebadet and Zeppelin Observatory shows deviations varying with season.
NILU
2022
The way Norway is spearheading electrification in the transport sector is of global interest. In this study, we used the Norwegian Emissions from Road Vehicle Exhaust (NERVE) model, a bottom-up high-resolution traffic emission model, to calculate all emissions in Norway (2009–2020) and evaluate potential co-benefit and trade-offs of policies to target climate change mitigation, air quality and socioeconomic factors. Results for municipal data with regard to traffic growth, road network influences, vehicle composition, emissions and energy consumption are presented. Light vehicle CO2 emissions per kilometer have been reduced by 22% since 2009, mainly driven by an increasing bio-fuel mixing and battery electric vehicles (BEV) share. BEVs are mostly located in and around the main cities, areas with young vehicle fleets, and strong local incentives. Beneficiaries of BEVs incentives have been a subset of the population with strong economic indicators. The incentivized growth in the share of diesel-fuelled passenger vehicles has been turned, and together with Euro6 emission standards, light vehicle NOx emissions have been halved since peaking in 2014. BEVs represent an investment in emission reductions in years to come, and current sales set Norway up for an accelerated decline in all exhaust emissions despite the continual growth in traffic.
2022
2022
To assess how climate-sensitive factors may affect the exposure to organochlorines (OCs) and perfluoroalkyl substances (PFASs), we monitored concentrations in eggs of the common goldeneye (Bucephala clangula) over two decades (1999–2019) in central Norway. The goldeneye alternates between marine and freshwater habitats and is sensitive to climate variation, especially due to alterations in ice conditions which may affect feeding conditions. We assessed how biological factors such as diet (stable isotopes δ13C and δ15N), the onset of egg laying, and physical characteristics such as winter climate (North Atlantic Oscillation: NAOw) influenced exposure. We predicted compounds to show different temporal trends depending on whether they were still in production (i.e. some PFASs) or have been banned (i.e. legacy OCs and some PFASs). Therefore, we controlled for potential temporal trends in all analyses. There were declining trends for α- and γ-hexachlorocyclohexane (HCH), oxychlordane, cis-chlordane, cis-nonachlor, p,p′-dichlorodiphenyltrichloroethane (p.p′-DDT) and less persistent polychlorinated biphenyl (PCB) congeners (e.g. PCB101). In contrast, the dominant compounds, such as p,p′-dichlorodiphenyldichloroethylene (p,p′-DDE) and persistent PCB congeners, were stable, whereas hexachlorobenzene (HCB) increased over time. Most OCs were positively related to δ15N, suggesting higher exposure in birds feeding at upper trophic levels. Chlordanes and HCB were positively associated with δ13C, indicating traces of marine input for these compounds, whereas the relationships to most PCBs were negative. Among PFASs, perfluorooctanesulfonamide (PFOSA) and perfluorohexane sulfonic acid (PFHxS) declined. Most PFASs were positively associated with δ13C, whereas there were no associations with δ15N. Egg laying date was positively associated to perfluoroheptanesulfonic acid (PFHpS), perfluorooctanesulfonic acid (PFOS) and perfluorooctanoic acid (PFOA), suggesting that some of the PFAS load originated from the wintering locations. Although NAOw had little impact on the exposure to organohalogenated contaminants, factors sensitive to climate change, especially diet, were associated with the exposure to OHCs in goldeneyes.
2022
Advanced in vitro models are needed to support next-generation risk assessment (NGRA), moving from hazard assessment based mainly on animal studies to the application of new alternative methods (NAMs). Advanced models must be tested for hazard assessment of nanomaterials (NMs). The aim of this study was to perform an interlaboratory trial across two laboratories to test the robustness of and optimize a 3D lung model of human epithelial A549 cells cultivated at the air–liquid interface (ALI). Potential change in sensitivity in hazard identification when adding complexity, going from monocultures to co- and tricultures, was tested by including human endothelial cells EA.hy926 and differentiated monocytes dTHP-1. All models were exposed to NM-300K in an aerosol exposure system (VITROCELL® cloud-chamber). Cyto- and genotoxicity were measured by AlamarBlue and comet assay. Cellular uptake was investigated with transmission electron microscopy. The models were characterized by confocal microscopy and barrier function tested. We demonstrated that this advanced lung model is applicable for hazard assessment of NMs. The results point to a change in sensitivity of the model by adding complexity and to the importance of detailed protocols for robustness and reproducibility of advanced in vitro models
2022
Evaluation and Global-Scale Observation of Nitrous Oxide from IASI on Metop-A
Nitrous oxide (N2O) is a greenhouse gas difficult to estimate by satellite because of its weak spectral signature in the infra-red band and its low variability in the troposphere. Nevertheless, this study presents the evaluation of new tropospheric N2O observations from the Infrared Atmospheric Sounder Interferometer (IASI) on Metop-A using the Toulouse N2O Retrieval Version 2.0 tool. This tool is based on the Radiative Transfer for Tiros Operational Vertical sounder (RTTOV) model version 12.3 coupled to the Levenberg-Marquardt optimal estimation method enabling the simultaneous retrieval of methane, water vapour, temperature profiles together with surface temperature and emissivity within the 1240–1350 cm−1 window. In this study, we focused on the upper troposphere (300 hPa) where the sensitivity of IASI is significant. The IASI N2O data has been evaluated using aircraft N2O observations from the High-performance Instrumented Airborne Platform for Environmental Research Pole-to-Pole Observations (HIPPO) campaigns in 2009, 2010, and 2011 and from the National Oceanic and Atmospheric Administration’s (NOAA) Global Greenhouse Gas Reference Network (GGGRN) in 2011. In addition, we evaluated the IASI N2O using ground-based N2O measurements from 9 stations belonging to the Network for the Detection of Atmospheric Composition Change (NDACC). We found a total random error of ∼2 ppbv (0.6%) for one single retrieval at 300 hPa. Under favorable conditions, this error is also found in the vertical level pressure range 300–500 hPa. It decreases rapidly to ∼0.4 ppbv (0.1%) when we average on a 1° × 1° box. In addition, independent observations allows the estimation of bias with the IASI TN2OR v2.0 N2O. The bias between IASI and aircraft N2O data at 300 hPa is ∼1.0 ppbv (∼0.3%). We found an estimated random error of ∼2.3 ppbv (∼0.75%). This study also shows relatively high correlations between IASI data and aircraft in situ profiles but more varying correlations over the year 2011 depending on the location between IASI and NDACC remote sensing data. Finally, we present daily, monthly, and seasonal IASI N2O horizontal distributions in the upper troposphere as well as cross sections for different seasons that exhibit maxima in the Tropical band especially over Africa and South America.
2022