Constraints on ship NOx emissions in Europe using GEOS-Chem and OMI satellite NO2 observations

We present a top-down ship NOx emission inventory for the Baltic Sea, the North Sea, the Bay of Biscay and the Mediterranean Sea based on satellite-observed tropospheric NO2 columns of the Ozone Monitoring Instrument (OMI) for 2005–2006. We improved the representation of ship emissions in the GEOS-Chem chemistry transport model, and compared simulated NO2 columns to consistent satellite observations. Relative differences between simulated and observed NO2 columns have been used to constrain ship emissions in four European seas (the Baltic Sea, the North Sea, the Bay of Biscay and the Mediterranean Sea) using a mass-balance approach, and accounting for non-linear sensitivities to changing emissions in both model and satellite retrieval. These constraints are applied to 39 % of total top-down European ship NOx emissions, which amount to 0.96 Tg N for 2005, and 1.0 Tg N for 2006 (11–15% lower than the bottom-up EMEP ship emission inventory). Our results indicate that EMEP emissions in the Mediterranean Sea are too high (by 60%) and misplaced by up to 150 km, which can have important consequences for local air quality simulations. In the North Sea ship track, our top-down emissions amount to 0.05 Tg N for 2005 (35% lower than EMEP). Increased top-down emissions were found for the Baltic Sea and the Bay of Biscay ship tracks, with totals in these tracks of 0.05 Tg N (131% higher than EMEP) and 0.08 Tg N for 2005 (128% higher than EMEP), respectively. Our study explicitly accounts for the (non-linear) sensitivity of satellite retrievals to changes in the a priori NO2 profiles, as satellite observations are never fully independent of model information (i.e. assumptions on vertical NO2 profiles). Our study provides for the first time a space-based, top-down ship NOx emission inventory, and can serve as a framework for future studies to constrain ship emissions using satellite NO2 observations in other seas

Constraints on ship NOx emissions in Europe using GEOS-Chem and OMI satellite NO2 observations

We present a top-down ship NOx emission inventory for the Baltic Sea, the North Sea, the Bay of Biscay and the Mediterranean Sea based on satellite-observed tropospheric NO2 columns of the Ozone Monitoring Instrument (OMI) for 2005–2006. We improved the representation of ship emissions in the GEOS-Chem chemistry transport model, and compared simulated NO2 columns to consistent satellite observations. Relative differences between simulated and observed NO2 columns have been used to constrain ship emissions in four European seas (the Baltic Sea, the North Sea, the Bay of Biscay and the Mediterranean Sea) using a mass-balance approach, and accounting for nonlinear sensitivities to changing emissions in both model and satellite retrieval. These constraints are applied to 39% of total top-down European ship NOx emissions, which amount to 0.96 TgN for 2005, and 1.0 TgN for 2006 (11–15% lower than the bottom-up EMEP ship emission inventory). Our results indicate that EMEP emissions in the Mediterranean Sea are too high (by 60 %) and misplaced by up to 150 km, which can have important consequences for local air quality simulations. In the North Sea ship track, our top-down emissions amount to 0.05 TgN for 2005 (35% lower than EMEP). Increased top-down emissions were found for the Baltic Sea and the Bay of Biscay ship tracks, with totals in these tracks of 0.05 TgN (131% higher than EMEP) and 0.08 TgN for 2005 (128% higher than EMEP), respectively. Our study explicitly accounts for the (non-linear) sensitivity of satellite retrievals to changes in the a priori NO2 profiles, as satellite observations are never fully independent of model information (i.e. assumptions on vertical NO2 profiles). Our study provides for the first time a space-based, top-down ship NOx emission inventory, and can serve as a framework for future studies to constrain ship emissions using satellite NO2 observations in other seas

Comparison of base-line and chemical-induced transcriptomic responses in HepaRG and RPTEC/TERT1 cells using TempO-Seq

The utilisation of genome-wide transcriptomics has played a pivotal role in advancing the field of toxicology, allowing the mapping of transcriptional signatures to chemical exposures. These activities have uncovered several transcriptionally regulated pathways that can be utilised for assessing the perturbation impact of a chemical and also the identification of toxic mode of action. However, current transcriptomic platforms are not very amenable to high-throughput workflows due to, high cost, complexities in sample preparation and relatively complex bioinformatic analysis. Thus, transcriptomic investigations are usually limited in dose and time dimensions and are, therefore, not optimal for implementation in risk assessment workflows. In this study, we investigated a new cost-effective, transcriptomic assay, TempO-Seq, which alleviates the aforementioned limitations. This technique was evaluated in a 6-compound screen, utilising differentiated kidney (RPTEC/TERT1) and liver (HepaRG) cells and compared to non-transcriptomic label-free sensitive endpoints of chemical-induced disturbances, namely phase contrast morphology, xCELLigence and glycolysis. Non-proliferating cell monolayers were exposed to six sub-lethal concentrations of each compound for 24 h. The results show that utilising a 2839 gene panel, it is possible to discriminate basal tissue-specific signatures, generate dose-response relationships and to discriminate compound-specific and cell type-specific responses. This study also reiterates previous findings that chemical-induced transcriptomic alterations occur prior to cytotoxicity and that transcriptomics provides in depth mechanistic information of the effects of chemicals on cellular transcriptional responses. TempO-Seq is a robust transcriptomic platform that is well suited for in vitro toxicity experiments.Horizon 2020(H2020)68100

A mode-of-action ontology model for safety evaluation of chemicals: outcome of a series of workshops on repeated dose toxicity

Repeated dose toxicity evaluation aims at assessing the occurrence of adverse effects following chronic or repeated exposure to chemicals. Non-animal approaches have gained importance in the last decades because of ethical considerations as well as due to scientific reasons calling for more human-based strategies. A critical aspect of this challenge is linked to the capacity to cover a comprehensive set of interdependent mechanisms of action, link them to adverse effects and interpret their probability to be triggered in the light of the exposure at the (sub)cellular level. Inherent to its structured nature, an ontology addressing repeated dose toxicity could be a scientific and transparent way to achieve this goal. Additionally, repeated dose toxicity evaluation through the use of a harmonized ontology should be performed in a reproducible and consistent manner, while mimicking as accurately as possible human physiology and adaptivity. In this paper, the outcome of a series of workshops organized by Cosmetics Europe on this topic is reported. As such, this manuscript shows how experts set critical elements and ways of establishing a mode-of-action ontology model as a support to risk assessors aiming to perform animal-free safety evaluation of chemicals based on repeated dose toxicity data

A21 HIV-1 sub-subtype F1 outbreak among MSM in Belgium

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Earlier initiation of antiretroviral treatment coincides with an initial control of the HIV-1 sub-subtype F1 outbreak among men-having-sex-with-men in Flanders, Belgium

Human immunodeficiency virus type 1 (HIV-1) non-B subtype infections occurred in Belgium since the 1980s, mainly amongst migrants and heterosexuals, whereas subtype B predominated in men-having-sex-with-men (MSM). In the last decade, the diagnosis of F1 sub-subtype in particular has increased substantially, which prompted us to perform a detailed reconstruction of its epidemiological history. To this purpose, the Belgian AIDS Reference Laboratories collected HIV-1 pol sequences from all sub-subtype F1-infected patients for whom genotypic drug resistance testing was requested as part of routine clinical follow-up. This data was complemented with HIV-1 pol sequences from countries with a high burden of F1 infections or a potential role in the global origin of sub-subtype F1. The molecular epidemiology of the Belgian subtype F1 epidemic was investigated using Bayesian phylogenetic inference and transmission dynamics were characterized based on birth-death models. F1 sequences were retained from 297 patients diagnosed and linked to care in Belgium between 1988 and 2015. Phylogenetic inference indicated that among the 297 Belgian F1 sequences, 191 belonged to a monophyletic group that mainly contained sequences from people likely infected in Belgium (OR 26.67, 95% CI 9.59-74.15), diagnosed in Flanders (OR 7.28, 95% CI 4.23-12.53), diagnosed at a recent stage of infection (OR 7.19, 95% CI 2.88-17.95) or declared to be MSM (OR 34.8, 95% CI 16.0-75.6). Together with a Spanish clade, this Belgian clade was embedded in the genetic diversity of Brazilian subtype F1 strains and most probably emerged after one or only a few migration events from Brazil to the European continent before 2002. The origin of the Belgian outbreak was dated back to 2002 (95% higher posterior density 2000-2004) and birth-death models suggested that its extensive growth had been controlled (Re < 1) by 2012, coinciding with a time period where delay in antiretroviral treatment initiation substantially declined. In conclusion, phylogenetic reconstruction of the Belgian HIV-1 sub-subtype F1 epidemic illustrates the introduction and substantial dissemination of viral strains in a geographically restricted risk group that was most likely controlled by effective treatment as prevention.publishersversionpublishe

Application of evidence-based methods to construct mechanism-driven chemical assessment frameworks

The workshop titled “Application of evidence-based methods to construct mechanism-driven chemical assessment frameworks” was co-organized by the Evidence-based Toxicology Collaboration and the European Food Safety Authority (EFSA) and hosted by EFSA at its headquarters in Parma, Italy on October 2 and 3, 2019. The goal was to explore integration of systematic review with mechanistic evidence evaluation. Participants were invited to work on concrete products to advance the exploration of how evidence-based approaches can support the development and application of adverse outcome pathways (AOP) in chemical risk assessment. The workshop discussions were centered around three related themes: 1) assessing certainty in AOPs, 2) literature-based AOP development, and 3) integrating certainty in AOPs and non-animal evidence into decision frameworks. Several challenges, mostly related to methodology, were identified and largely determined the workshop recommendations. The workshop recommendations included the comparison and potential alignment of processes used to develop AOP and systematic review methodology, including the translation of vocabulary of evidence-based methods to AOP and vice versa, the development and improvement of evidence mapping and text mining methods and tools, as well as a call for a fundamental change in chemical risk and uncertainty assessment methodology if to be conducted based on AOPs and new approach methodologies (NAM). The usefulness of evidence-based approaches for mechanism-based chemical risk assessments was stressed, particularly the potential contribution of the rigor and transparency inherent to such approaches in building stakeholders’ trust for implementation of NAM evidence and AOPs into chemical risk assessment

Characterization of the effects of Atosiban on uterine electromyograms recorded in women with threatened preterm labor

[EN] Although research studies using electrohysterography on women without tocolytic therapy have shown its potential for preterm birth diagnosis, tocolytics are usually administered in emergency rooms at the first sign of threatened preterm labor (TPL). Information on the uterine response during tocolytic treatment could prove useful for the development of tools able to predict true preterm deliveries under normal clinical conditions. The aim of this study was thus to analyze the effects of Atosiban on Electrohysterogram (EHG) parameters and to compare its effects on women who delivered preterm (WDP) and at term (WDT). Electrohysterograms recorded in different Atosiban therapy stages (before, during and after drug administration) on 40 WDT and 27 WDP were analyzed by computing linear, and non-linear EHG parameters. Results reveal that Atosiban does not greatly affect the EHG signal amplitude, but does modify its spectral content and reduces the energy associated with the fast wave high component in both WDP and WDT, with a faster response in the latter. EHG signal complexity remained constant in WDT, while it increased in WDP until it reached similar values to WDT during Atosiban treatment. The spectral and complexity parameters were able to separate (p < 0.05) WDT and WDP prior to and during tocolytic treatment and before and after treatment, respectively. The results pave the way for developing better and more reliable medical decision support systems based on EHG for preterm delivery prediction in TPL women in clinical scenarios.This work received financial support from the Spanish Ministry of Economy and Competitiveness and the European Regional Development Fund (DPI2015-68397-R), VLC/Campus (UPV-FE-2018-B03) and by Conselleria de Educación, Investigación, Cultura y Deporte, Generalitat Valenciana (GV/2018/104).Mas-Cabo, J.; Prats-Boluda, G.; Ye Lin, Y.; Alberola Rubio, J.; Perales, A.; Garcia-Casado, J. (2019). Characterization of the effects of Atosiban on uterine electromyograms recorded in women with threatened preterm labor. Biomedical Signal Processing and Control. 52:198-205. https://doi.org/10.1016/j.bspc.2019.04.001S1982055