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Ribosomally synthesized and posttranslationally modified peptides (RiPPs) are a structurally diverse group of natural products that bacteria employ in their survival strategies. Herein, we characterized the structure, the biosynthetic pathway, and the mode of action of a RiPP family called bufferins. With thousands of homologous biosynthetic gene clusters throughout the bacterial phylogenetic tree, bufferins form by far the largest family of RiPPs modified by multinuclear nonheme iron-dependent oxidases (MNIO, DUF692 family). Using Caulobacter vibrioides bufferins as a model, we showed that the conserved Cys residues of their precursors are transformed into 5-thiooxazoles, further expanding the reaction range of MNIO enzymes. This rare modification is installed in conjunction with a partner protein of the DUF2063 family. Bufferin precursors are rare examples of bacterial RiPPs found to feature an N-terminal Sec signal peptide allowing them to be exported by the ubiquitous Sec pathway. We reveal that bufferins are involved in copper homeostasis, and their metal-binding propensity requires the thiooxazole heterocycles. Bufferins enhance bacterial growth under copper stress by complexing excess metal ions. Our study thus describes a large family of RiPP metallophores and unveils a widespread but overlooked metal homeostasis mechanism in bacteria., Competing Interests: Competing interests statement:The authors declare no competing interest.

The adaptation of Yersinia pestis , the flea-borne plague agent, to fluctuating environmental conditions is essential for the successful colonization of the flea vector. A previous comparative transcriptomic analysis showed that the Cpx pathway of Y. pestis is up-regulated in infected fleas. The CpxAR two-component system is a component of the envelope stress response and is critical for maintaining the integrity of the cell. Here, a phenotypic screening revealed a survival defect of the cpxAR mutant to oxidative stress and copper. The measured copper concentration in the digestive tract contents of fed fleas increased fourfold during the digestive process. By direct analysis of phosphorylation of CpxR by a Phos-Tag gel approach, we demonstrated that biologically relevant concentrations of copper triggered the system. Then, a competitive challenge highlighted the role of the CpxAR system in bacterial fitness during flea infection. Lastly, an in vitro sequential exposure to copper and then H 2 O 2 to mimic the flea suggests a model in which, within the insect digestive tract, the CpxAR system would be triggered by copper, establishing an oxidative stress response., Importance: The bacterium Yersinia pestis is the agent of flea-borne plague. Our knowledge of the mechanisms used by the plague bacillus to infect the flea vector is limited. The up-regulation of the envelope stress response under the control of the Cpx signaling pathway was previously shown in a transcriptomic study. Here, our in vivo and in vitro approaches suggest a model in which Y. pestis uses the CpxAR phosphorelay system to sense and respond to the copper present in the flea gut, thereby optimizing the flea gut colonization. In other words, the system is essential for bacterial fitness in the flea., Competing Interests: The authors declare no conflict of interest.

Sea-salt aerosols (SSA) are one of the key natural aerosols in our atmosphere, consisting predominantly of sodium chloride (NaCl). Throughout their atmospheric transport, these aerosols undergo complex internal mixing, giving rise to a rich variety of inorganic and organic species, including dicarboxylic acids. This study investigates firstly the composition and deliquescence properties of coarse particles containing pure malonic acid (MA 2 , CH 2 (COOH) 2 ) and internally mixed NaCl and MA 2 , by means of an acoustic levitation system coupled with a Raman microspectrometer. Secondly, we report here the first experimental observation and characterization of the products arising from photochemical reactions under UV-Visible irradiation (338 ≤ λ ≤ 414 nm) in the absence of an oxidant under acoustic levitation conditions in MA 2 and NaCl/MA 2 aerosols. Furthermore, the impact of photodegradation on the hygroscopic properties of these particles is examined. We confirmed the irreversible formation of monosodium malonate (NaMA, HOOCCH 2 COONa), which coexists with NaCl or MA 2 on non-irradiated particles. We also demonstrated the formation of oxalic acid (OA 2 , HOOC-COOH) within irradiated MA 2 droplets and the appearance of glyoxylic acid (GlyA, HCOCOOH) in NaCl containing droplets. The photolysis process exerts a marked effect on the hygroscopic properties of the particles, resulting in a shift in deliquescence transitions toward higher relative humidity (RH) values. This study contributes to the understanding of the intricate physicochemical processes involved in SSA during their atmospheric transport. Likewise, this work sheds light on the impacts of these types of aerosols on cloud formation and climate change., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Purpose: Suicide is a major cause of preventable death worldwide. Adequate training in risk assessment and intervention is key to suicide prevention. The use of simulation (role plays, simulated patients, virtual reality…) for practical training is a promising tool in mental health. The purpose of this study was to assess the effectiveness of simulation training in suicide risk assessment and intervention for healthcare professionals and gatekeepers., Methods: We conducted a systematic review in Medline and PsycINFO up to 31 July 2021 of randomized controlled trials (RCTs), non-randomized controlled trials, and pre/post-test studies. RCTs were furthermore included in a meta-analysis. We assessed the methodological quality of all studies with the Medical Education Research Study Quality Instrument, and the Cochrane Risk of Bias tool 2.0 for RCTs. Primary outcomes were changes in Kirkpatrick criteria: attitudes, skills, knowledge, behaviors, and patient outcomes., Results: We included 96 articles representing 43,656 participants. Most pre/post-test (n = 65) and non-randomized controlled (n = 14) studies showed significant improvement in attitudes, skills, knowledge, and behaviors. The meta-analysis of 11 RCTs showed positive changes in attitudes immediately after training and at 2-4 months post-training; in self-perceived skills at 6 months post-training; but not in factual knowledge. Studies assessing benefits for patients are still limited., Conclusions: The heterogeneity of methodological designs, interventions, and trained populations combined with a limited number of RCTs and studies on patients' outcomes limit the strength of the evidence. However, preliminary findings suggest that simulation is promising for practical training in suicidal crisis intervention and should be further studied.

Background: Empathetic listening can be particularly challenging with patients presenting pressured speech, while time pressure and costs limit practitioners' availability. We aimed to explore general practitioners' (GPs') experiences when encountering a patient with pressured speech without pathological syndrome., Methods: Using a thematic analysis method, 19 semi-structured interviews were conducted with GPs purposively sampled in Ile-de-France region., Results: Three themes emerged. First, misgivings were aroused when meeting a patient with pressured speech, including frustration, displeasure, and a struggle to maintain focus. Second, huge efforts were needed to adhere to the appropriate clinical reasoning and care for these patients who need more time and energy. The very definition of this condition varies from one clinician to another, and for some, psychiatric conditions were systematically associated. Third, implementation of specific strategies was required to adjust to these patients: trying to create distance with the patient, to organize a framework in which the patient with pressured speech can express him or herself, and even strategies to increase GPs' availability., Conclusion: The time and energy required to provide adequate care for patients presenting with pressured speech make it quite challenging, and this builds up pressure in the waiting room. But when medical demands take this form, there is a risk that clinicians will reject the patient or refer early to mental health services, leading to growing feelings of abandonment, the neglect of organic issues, and medical nomadism. Initial and continuing medical training focussing on advanced communication skills and multifocal approaches can foster long-term follow-up., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Plastic waste and its fragments (microplastics; <5 mm) have been observed in almost all types of environments. However, the mechanisms underlying the flow and transport processes of plastics are unknown. This is particularly valid for river sediments, where complex interactions occur between particles and influence their vertical and horizontal distribution patterns. In this study, we investigated the vertical redistribution of 14 pristine microplastics (MPs) with different densities, sizes, and shapes within disturbed sediment without lateral transport (i.e., low-velocity flow). MPs were spiked into sediments (height: 8 cm) in a column with a height of 1 m (diameter: 6 cm) filled to the top with water. The sediment was perturbed by turning the column upside-down to simulate remobilization and the subsequent deposition of sediment. After the complete sedimentation of the particles, the water column was filtered and the sediment was cut into vertical sections. MPs were then extracted from the sediment using sieves and a density separation method, and were counted under a stereomicroscope. Low-density polymers were mainly recovered in the water column and at the surface of the sediment, whereas high-density polymers were found within all sediment sections. The vertical distribution of high-density polymers changes primarily with the sediment grain size. The distribution of each polymer type changes depending on the size and/or shape of the particles with complex interactions. The observed distributions were compared with the expected distributions based only on the vertical velocity formulas. Overall, the formulas used did not explain the sedimentation of a portion of low-density polymers and predicted a lower distribution in the sediment than those observed in the experiment. In conclusion, this study highlights the importance of considering MPs as multi-dimensional particles and provides clues to understand their fate in low-velocity flow systems, considering that they undergo scavenging in sediments., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

The Solidification/Stabilization method for dredged sediments remediation can be very effective for the immobilization of trace metal (TM) pollutants. The ordinary Portland cement (OPC) is largely used in this process. Nevertheless, the mechanical performance of treated sediments can be considerably improved at long term using ground granulated blast furnace slag (GGBS) as was shown in (Gutsalenko et al., 2018). Therefore, it is worth investigating whether this new binder is also relevant in terms of stabilization and mechanisms involved in this process. To meet this objective, leaching test, total attack, sequential extraction (SE) and X-ray Adsorption Near-Edge Structure (XANES) experiments measurements were performed. The results of the leaching tests conducted as part of the study are promising for the use of GGBS in the treatment of the real case project Dublin sediment and it outperforms the OPC-based treatment.. The sequential extraction method was applied to evaluate the potential risks of toxic elements according to their repartition in the Dublin sediment matrix and predicts the release of metals under different environmental conditions. It shows a lower perturbation rate of pollutants with the GGBS-based binder. Finally, XANES experiments demonstrate changes in the chemical environment of Zn and Cu after the treatment of the sediment with OPC compared to the GGBS rich binder. Consequently, this study finds that it is more pertinent to use the GGBS-based binder in terms of trace metal stabilization., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Increase of water quality in aquatic systems has become a hot button issue in recent decades. However, with the aim to implement an effective remediation strategy, the first step is to identify the sources of diffuse and point-source pollution using several tracers. In urban areas, B isotopes, Gd enrichment, Cl - or carbamazepine concentrations can be used as wastewater treatment plant tracers. In this study, a focus was made on the quantification of a wide variety of inorganic compounds (elements, ions, isotopic ratios) all along the Marque River, a small stream located in Northern France receiving effluents coming from seven wastewater treatment plants (WWTPs). The objectives were (i) to determine the importance of the WWTPs discharge during low water events, (ii) to assess the efficiency of conventional tracers in quantifying the contribution of the WWTPs and (iii) to investigate new potential tracers less commonly used. The results have shown, through statistical analyses ANOVA (Analysis Of Variance) tests, PCA (Principal Component Analysis) and contribution calculations, that the WWTPs discharges strongly impact the water composition of all the watercourse and particularly during the first 6 km. However, due to high discharges of wastewaters not always well treated, some classical indicators (e.g. B, Rb/Sr) have shown limitations when used alone. The use of a set of relevant tracers including alkali metals could therefore be one solution for overcoming such a problem. Finally, other indicators like Rb/B or Gd/Pt ratios may also be a way to tackle this issue; they are indeed promising to discriminate the source of wastewaters., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

The way in which aquatic systems is sampled has a strong influence on our understanding of them, especially when they are highly dynamic. High frequency sampling has the advantage over spot sampling for representativeness but leads to a high amount of analysis. This study proposes a new methodology to choose when sampling accurately with an automated sampler coupled with a high frequency (HF) multiparameter probe. After each HF measurement, an optimised sampling algorithm (OSA) determines on-the-fly the relevance of taking a new sample in relation to previous waters already collected. Once the OSA was optimised, considering the number of HF parameters and their variabilities, it was demonstrated through a study case that the number of samples could be significantly reduced, while still covering periods of low and high variabilities. The comparison between the total HF dataset and the sampled subdataset shows that physicochemical parameter variability is preserved (Pearson correlations > 0.96) as well as the multiparameter variability (PCA axes remained similar with Tucker congruence > 0.99). This algorithm simplifies HF studies by making it easier to take samples during brief phenomena such as storms or accidental spills that are often poorly monitored. In addition, it optimises the number of samples to be taken to correctly describe a system and thus reduce the human and financial costs of these environmental studies., (Copyright © 2022. Published by Elsevier Ltd.)

Aims: Mental disorders constitute one of the main causes of disease and disability worldwide. While nurses are often at the frontline of mental health care, they have limited access to dedicated psychiatric training opportunities. Simulation training may foster the development of the appropriate competencies required when supporting people with mental disorders. To evaluate the effectiveness of simulation training in psychiatry for nursing students, nurses and nurse practitioners., Design: Systematic review and meta-analysis., Data Sources: Eight electronic databases, trial registries, key journals and reference lists of selected studies were searched from inception to August 20, 2020 without language restriction., Review Methods: We included randomized and non-randomized controlled studies and single group pre/post studies. Cochrane Risk of Bias tool 2.0 was used for randomized controlled study appraisal, and the Medical Education Research Study Quality instrument was completed for all other studies. Meta-analysis was restricted to randomized controlled studies. The other studies were synthesized narratively. The main outcomes were based on Kirkpatrick levels., Results: A total of 118 studies (6738 participants) were found. Interventions included simulated patients (n = 55), role-plays (n = 40), virtual reality (n = 12), manikins (n = 9) and voice simulations (n = 9). Meta-analyses based on 11 randomized controlled studies found a significant large effect size on skills at immediate post-test for simulation compared with active control; and a small and medium effect size on learners' attitudes for simulation compared with inactive control, at immediate post-test and at three-month follow-up respectively. Three quarters of non-randomized controlled studies and pre/post-tests assessing attitudes and skills showed significant differences, and three quarters of participants in randomized controlled studies and pre/post-tests showed significant differences in behaviours. Among the few studies assessing people with mental health outcomes, almost all reported significant differences., Conclusion: These findings support the effectiveness of simulation training in psychiatric nursing throughout professional development grades, despite heterogeneity in methods and simulation interventions., (© 2021 John Wiley & Sons Ltd.)

Capitella spp. is considered as an important ecological indicator of eutrophication due to its high densities in organic-rich, reduced, and sometimes polluted coastal ecosystems. We investigated whether such ability to cope with adverse ecological contexts might be a response to the microorganisms these worms are associated with. In populations from the French Atlantic coast (Roscoff, Brittany), we observed an epibiotic association covering the tegument of 20-30% specimens from an anthropized site while individuals from a reference, non-anthropized site were devoid of any visible epibionts. Using RNAseq, molecular and microscopic analyses, we described and compared the microbial communities associated with the epibiotic versus the non-epibiotic specimens at both locations. Interestingly, data showed that the epibiosis is characterized by sulfur-oxidizing bacteria among which the giant bacterium Thiomargarita sp., to date only described in deep sea habitats. Survey of Capitella combined with the geochemical analysis of their sediment revealed that epibiotic specimens are always found in muds with the highest concentration of sulfides, mostly during the summer. Concomitantly, tolerance tests demonstrated that the acquisition of epibionts increased survival against toxic level of sulfides. Overall, the present data highlight for the first time a peculiar plastic adaptation to seasonal variations of the habitat based on a transcient epibiosis allowing a coastal species to survive temporary harsher conditions., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Microplastics are small (<5 mm) fragments of plastic debris that are ubiquitous in oceans and terrestrial ecosystems. Studies on microplastics in sediment and soil matrices are particularly challenging because of the need to separate the plastics from the sediments. We investigated the efficiencies of 18 combinations of six extracting solutions (ESs) (oil, water, oil-in-water, NaCl, oil-in-NaCl, and NaI) and three isolation methods (IMs) (hand stirring, centrifugation, and aeration) for fine and coarse sediments, with low and high density polymers. IMs did not affect the extraction efficiency. Except in case of oil, all ESs enabled good extraction (84 ± 17%) of light polymers (PE and PE-ABS). NaI presented the best extraction efficiency (71 ± 17%) for the densest polymers (PET, PES, and PA). For these ESs, fibers were extracted at a lower efficiency than pellets and fragments, and sediment gran size did not affect the extraction. For other ESs, mean extraction rates ranged from 5% to 48%. Overall, the extraction efficiencies were lower than those found in the literature, despite repeating the separation process three times. The collection of floating materials remained a problem, as plastics tended to adhere to the glass wall. Our work will help the comparability between previous and future monitoring results and the selection of the most suitable protocols for future studies. This work clearly demonstrates also that there is no robust protocol for extracting all types and forms of microplastics from fine sediments and that research efforts to arrive at a reliable method remain by taking account the interaction of MPs with other particles as well as the electrostatic properties of MP., (Copyright © 2021 Elsevier B.V. All rights reserved.)

This study aiming to determine the optimal conditions to degrade an organophosphate pesticide diazinon (DZN) at low levels concentrations (μg.mL -1 ) and to identify the by-products generated. The degradation processes utilized were the Fenton and photo-Fenton. The iron concentration [Fe 2+ ], the hydrogen peroxide concentrations [H 2 O 2 ], and the solution pH are the investigated parameters. The Doehlert three-parameter experimental design was applied to model and optimize both degradation processes. The mathematical models suggested were assessed and validated by application of analysis of variances ANOVA. In the case of Fenton process, the greatest yield of degradation (79%) was obtained at [Fe 2+ ] = 35 mg.L -1 (0.63 mmol.L -1 ), [H 2 O 2 ] = 423 mg.L -1 (12.44 mmol.L -1 ), and pH = 5.0. In photo-Fenton process, the maximum yield of degradation (96%) was obtained under the conditions of [Fe 2+ ] = 29 mg.L -1 (0.52 mmol.L -1 ), [H 2 O 2 ] = 258 mg.L -1 (7.59 mmol.L -1 ) and pH = 4.6. QuEChERS (quick, easy, cheap, effective, rugged, and safe), as extraction technique, and GC-MS/MS (gas chromatography coupled with triple quadrupole mass spectrometry) were used to identify the by-products degradation of DZN. The identified compounds are diazoxon, triethyl phosphate, triethyl thiophosphate, 2-isopropyl-5-ethyl-6-methylpyrimidine-4-ol, 2-isopropyl-6-methylpyrimidine-4-ol (IMP) and hydroxydiazinon. Three possible pathways for diazinon degradation have been suggested and the hydroxylation, oxidation and hydrolysis are likely probable degradation mechanisms., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

The performance of the newly developed DGT technique for the platinum group elements (PGEs) rhodium (Rh), platinum (Pt) and palladium (Pd) was evaluated in two tributaries of the Scheldt River, the Marque River close to the city of Lille (France), and the Zenne River which flows through the city of Brussels (Belgium). In the Marque River, an interlaboratory comparison was performed between the two laboratories where the DGT techniques dedicated to PGEs were developed (AMGC, VUB & LASIRE, U-Lille). PGEs were also analysed in an effluent of a Brussels hospital and monthly grab sampling was performed at the wastewater treatments plants (WWTPs) of Brussels. The concentrations of the 3 elements are higher in the Zenne River than in the Marque River and much higher Pt concentrations are found in the hospital effluent. Good agreement for Pt was observed between the three selected chelating resins and a relatively good agreement was observed between the two laboratories using the same chelating resin, whereas lower results were observed with the anion-exchange resin. Larger discrepancies between the two laboratories were observed for Pd and no comparison could be made for Rh due to the low natural concentrations. The results show that in small urban rivers with high impact of urbanization, WWTPs are an important source of Pt, resulting from the use of anticancer drugs in hospitals and households. The limited retention of PGEs in WWTPs results in increased concentrations in urban rivers downstream. For Pd and Rh, similar trends were found with other traffic related elements such as Cu, Zn and Pb, showing the highest concentrations in waters collecting runoff from a highway. The data show that these elements, together with Gd, can be useful to trace specific pollution sources and their dispersion., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

The Isotrace CNRS workgroup in collaboration with National Research Council of Canada has characterized a number of trace element mass fractions and isotope ratios currently not certified in AQUA-1 natural drinking water reference material (NRC Canada). This survey further expands the use of this material as a tool for environmental quality control, method validation, and method development tool for the international community. Simultaneously, the SLRS-6 river water was analyzed as quality control and also in order to compare both water characteristics, which were sampled in the same area but having undergone different treatment. Mass fractions for B, Cs, Li, Ga, Ge, Hf, Nb, P, Rb, Rh, Re, S, Sc, Se, Si, Sn, Th, Ti, Tl, W, Y, Zr, REEs, and six isotopic ratios are proposed for Sr and Pb. Measurements were mostly performed using ICP-MS with various calibration approaches. The results are reported as consensus or indicative values depending on the number of available datasets, with their associated uncertainties., (© 2021. Springer-Verlag GmbH Germany, part of Springer Nature.)

Despite recognised benefits of Simulation-Based Education (SBE) in healthcare, specific adaptations required within psychiatry have slowed its adoption. This article aims to discuss conceptual and practical features of SBE in psychiatry that may support or limit its development, so as to encourage clinicians and educators to consider the implementation of SBE in their practice. SBE took off with the aviation industry and has been steadily adopted in clinical education, alongside role play and patient educators, across many medical specialities. Concurrently, healthcare has shifted towards patient-centred approaches and clinical education has recognised the importance of reflective learning and teaching centred on learners' experiences. SBE is particularly well-suited to promoting a holistic approach to care, reflective learning, emotional awareness in interactions and learning, cognitive reframing, and co-construction of knowledge. These features present an opportunity to enhance education throughout the healthcare workforce, and align particularly well to psychiatric education, where interpersonal and relational dimensions are at the core of clinical skills. Additionally, SBE provides a strategic opportunity for people with lived experience of mental disorders to be directly involved in clinical education. However, tenacious controversies have questioned the adequacy of SBE in the psychiatric field, possibly limiting its adoption. The ability of simulated patients (SPs) to portray complex and contradictory cognitive, psychological and emotional states has been questioned. The validity of SBE to develop a genuine empathetic understanding of patients, to facilitate a comprehensive multiaxial diagnostic formulation, or to develop flexible interpersonal skills has been criticised. Finally, SBE's relevance to developing complex psychotherapeutic skills is much debated, while issues such as symptom induction in SPs or patients involvement raise ethical dilemmas. These controversies can be addressed through adequate evidence, robust learning design, and high standards of practice. Well-designed simulated scenarios can promote a positive consideration of mental disorders and complex clinical skills. Shared guidelines and scenario libraries for simulation can be developed, with expert psychiatrists, patients and students involvement, to offer SPs and educators a solid foundation to develop training. Beyond scenario design, the nuances and complexities in mental healthcare are also duly acknowledged during the debriefing phases, providing a crucial opportunity to reflect on complex interpersonal skills or the role of emotions in clinicians' behaviour. Considered recruitment and support of SPs by clinical educators can help to maintain psychological safety and manage ethical issues. The holistic and reflexive nature of SBE aligns to the rich humanistic tradition nurtured within psychiatry and medicine, presenting the opportunity to expand the use of SBE to support a range of clinical skills and workforce competencies required in psychiatry., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Piot, Attoe, Billon, Cross, Rethans and Falissard.)

Plastic wastes and their fragments (microplastics, MPs < 5 mm) represent a global, persistent, and ubiquitous threat to ecosystems. Their sources, transfers, and fates are still poorly understood, especially in rivers. To fill this gap, sediments were collected from two dredging disposal sites along the Aa River (France). Four pits were dug, and triplicate samples were obtained at four depths (down to 140 cm). The sediments were sieved to 5 mm to collect macroplastics (MaPs). MPs were separated from the sediment based on density using a NaI solution (1.6 g/mL). Suspected plastics were analyzed with Fourier transform infrared spectroscopy. The studied sediments were found to be widely contaminated with concentrations ranging from 0.97 to 77 MaPs/kg and from 0.78 to 2800 MPs/kg, which were 1-4 orders of magnitude lower than those in most polluted European riverbeds. The MaPs were principally polyethylene, polypropylene, polystyrene, and polyvinyl chloride films, whereas the MPs were mainly polyamide and polyester fibers. The plastic concentrations and features of the two sites, which were filled at two different times, differed. Several factors occurring before and after dredging operations may explain these discrepancies. Nevertheless, no relationships with the sediment features were noted, and thus, one major driving force could not be identified. At the site scale, more than 1 ton of plastic could be stored. In conclusion, this study highlights the importance of dredged sediments for past plastic pollution studies and global plastic budget estimations.

The biogeochemical behavior of Cd, Co, Cr, Cu, Ni and Pb along the historically polluted Scheldt estuary (Belgium - The Netherlands) was investigated in this study. As never studied before in this area, labile trace metals were measured using the passive sampling technique of Diffusive Gradients in Thin-films (DGT), while total dissolved and particulate trace metal concentrations were assessed using classic active sampling techniques. This dual approach allowed us to highlight the variations of trace metal speciation and distribution in the estuarine surface waters, considering environmental and physicochemical gradients along the transect. The large data set obtained was then compared with literature data of historical measurements along the Scheldt (from 1980 until now), but also from other estuaries. As emphasized by our results, trace metal mobility and partitioning along the Scheldt estuary was mainly driven by biogeochemical reactions which were strongly influenced by gradients of specific estuarine physico-chemical parameters, such as salinity, turbidity, temperature and so on. Hence, all species of trace metals displayed a non-conservative behavior. More precisely, dissolved labile fractions of trace metals showed higher levels in the middle estuary, where many solubilization and remobilization processes occurred due to turbulent mixing mechanisms and an increasing salinity. Our study confirmed the decreasing trend historically observed for particulate metals along the Scheldt, as well as the rising concentrations recorded for dissolved trace metals which might also lead to an increase of their labile fraction measured by the DGT. Finally, these preliminary results suggested that a more regular monitoring of labile metal along the Scheldt estuary is essential to have an in-depth understanding of trace metal speciation and to review bioavailability of trace metals within estuarine ecosystems., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

The Chalk aquifer used for drinking-water production in the southwest of the Lille European Metropolis is threatened by the presence of chlorinated aliphatic hydrocarbons (CHCs), their concentrations in groundwater regularly exceeding the regulatory limits for drinking water in France. This hinders its use for drinking-water production. Understanding the dynamics and spatial distribution of CHC in the aquifer is a key factor for resource sustainability. For that purpose, an intensive monitoring was undertaken in several well fields and at different depths over eight years. To assess a possible migration and/or degradation of the compounds, the water column in several wells was sampled at various depths with passive samplers. Furthermore, CHC degradation mechanisms were investigated with compound-specific carbon-isotope analysis. The CHC concentrations and their distributions in the area depend on past and current industrial activity, causing plumes emphasized by pumping in the wells, such plumes being multi-source with no identified origin in most wells. In the south area of Les Ansereuilles, reductive dechlorination of tetrachloroethylene from a former industrial laundry highly impacted the surrounding area with its main degradation product cis-1,2-dichloroethylene. The same area is also affected by tetrachlroroethylene from several industrial laundries, textile factories and dyeing industries with also an anaerobic degradation. In the northern part of Les Ansereuilles, tetrachloroethylene, trichloroethane, trichloroethylene and 1,1-dichloroethylene were found as primary products, whereas cis-1,2-dichloroethylene appears to be an anaerobic degradation product of TCE. The other well fields (Houplin-Ancoisne, Seclin and Emmerin) are less impacted by CHC pollution, and it was shown that no CHC degradation occurred in the wells. However, the stratification of CHCs in the well-water columns, their constant concentration values over time caused by the large amount of available CHCs, and the minor degradation occurring in wells are of concern for water operators in the future., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Platinum group elements (PGEs) are among the least abundant in the continental crust. They have become excellent tracers of anthropogenic activities, particularly due to their use in catalytic converters or in the medical industry. However, their quantification in environmental matrices is still problematic because of their low concentrations combined with the presence of interfering elements. Preconcentration methods are therefore necessary to measure accurate concentrations. In this study, the quantification of Ir, Rh, Ru, Pd and Pt was studied in depth by focusing on two resins: AG MP-1 (anion exchange) and Purolite® S-920 (chelating) with the aim of developing passive Diffusive Gradients in Thin films (DGT) samplers as in-situ pre-concentration tools. The characteristics of both resins (e.g. adsorption, elution, selectivity, etc.) were studied and the diffusion coefficients of PGEs in different matrices were determined. For the first time, carcinostatic platinum-based drugs were also studied. Better rates and percentages of adsorption were observed for S-920 while AG MP-1 was more selective with regard to spectral interferents and easier to elute. The diffusion coefficients of PGEs were resin-dependent, particularly for carcinostatic platinum-based drugs. For the first time, the applicability of these DGT samplers dedicated to PGEs was demonstrated in the field after their deployment in two wastewater treatment plants in Northern France for which concentrations were found to range from few pg L -1 (Ir, Ru) to few ng L -1 (Pt)., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Copper is both essential and toxic to living beings, which tightly controls its intracellular concentration. At the host-pathogen interface, copper is used by phagocytic cells to kill invading microorganisms. We investigated copper homeostasis in Bordetella pertussis, which lives in the human respiratory mucosa and has no environmental reservoir. B. pertussis has considerably streamlined copper homeostasis mechanisms relative to other Gram-negative bacteria. Its single remaining defense line consists of a metallochaperone diverted for copper passivation, CopZ, and two peroxide detoxification enzymes, PrxGrx and GorB, which together fight stresses encountered in phagocytic cells. Those proteins are encoded by an original, composite operon assembled in an environmental ancestor, which is under sensitive control by copper. This system appears to contribute to persistent infection in the nasal cavity of B. pertussis-infected mice. Combining responses to co-occurring stresses in a tailored operon reveals a strategy adopted by a host-restricted pathogen to optimize survival at minimal energy expenditure.

The intertidal areas of the Hauts-de-France (English Channel - France) stand out for the occurrence of fragile ecosystems that are exposed to natural and human-induced stress. Over the last two centuries, the northern part of this region has experienced a strong human pressure, with the settlement of numerous activities (i.e., metallurgic factories, harbors, embankments). On the contrary, the southern part includes mostly natural areas. The whole region is influenced by a macrotidal regime. A multidisciplinary approach based on sedimentological (grain-size), geochemical (trace metals, biomarkers) and biological (foraminifera) proxies was used to unravel the contrasting environmental conditions in the Hauts-de-France. Three foraminiferal-types communities, which reflect different ecological characteristics at regional scale, were identified: 1) estuarine macrotidal assemblages (Haynesina germanica associated to Elphidiidae) in low impacted estuaries; 2) industrial-perturbed assemblages (H. germanica and Cribroelphidium excavatum) in harbor areas; and 3) infaunal-dominant assemblages (Bolivina variabilis and B. pseudoplicata) in embankment areas. The outcomes of this study show that a multiproxy procedure needs to be adopted for properly characterizing intertidal ecosystems, where human impacts and natural stresses overlap and are hard to disentangle., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Context: Most medical doctors are likely to work with patients experiencing mental health conditions. However, educational opportunities for medical doctors to achieve professional development in the field of psychiatry are often limited. Simulation training in psychiatry may be a useful tool to foster this development., Objectives: The purpose of this study was to assess the effectiveness of simulation training in psychiatry for medical students, postgraduate trainees and medical doctors., Methods: For this systematic review and meta-analysis, we searched eight electronic databases and trial registries up to 31 August 2018. We manually searched key journals and the reference lists of selected studies. We included randomised and non-randomised controlled studies and single group pre- and post-test studies. Our main outcomes were based on Kirkpatrick levels. We included data only from randomised controlled trials (RCTs) using random-effects models., Results: From 46 571 studies identified, we selected 163 studies and combined 27 RCTs. Interventions included simulation by role-play (n = 69), simulated patients (n = 72), virtual reality (n = 22), manikin (n = 5) and voice simulation (n = 2). Meta-analysis found significant differences at immediate post-tests for simulation compared with active and inactive control groups for attitudes (standardised mean difference [SMD] = 0.52, 95% confidence interval [CI] 0.31-0.73 [I 2  = 0.0%] and SMD = 0.28, 95% CI 0.04-0.53 [I 2  = 52.0%], respectively), skills (SMD = 1.37, 95% CI 0.56-2.18 [I 2  = 93.0%] and SMD = 1.49, 95% CI 0.39-2.58 [I 2  = 93.0%], respectively), knowledge (SMD = 1.22, 95% CI 0.57-1.88 [I 2  = 0.0%] and SMD = 0.72, 95% CI 0.14-1.30 [I 2  = 80.0%], respectively), and behaviours (SMD = 1.07, 95% CI 0.49-1.65 [I 2  = 68.0%] and SMD = 0.45, 95% CI 0.11-0.79 [I 2  = 41.0%], respectively). Significant differences in terms of patient benefit and doctors' behaviours and skills were found at the 3-month follow-up., Conclusions: Despite heterogeneity in methods and simulation interventions, our findings demonstrate the effectiveness of simulation training in psychiatry training., (© 2020 Association for the Study of Medical Education and John Wiley & Sons Ltd.)

Mercury (Hg) is a pollutant of global concern owing to its great toxicity even at very low concentrations. Its toxicity depends on its chemical forms evidencing the importance to study its speciation. Dissolved Hg (Hg (d) ) and methylmercury (MeHg (d) ) monitoring in surface freshwaters represents a great challenge because of their very low concentrations and substantial temporal variability at different timescales. The Hg (d) temporal variability depends on the environmental conditions such as the hydrology, water temperature, redox potential (Eh), and solar photo cycle. Passive samplers represent an alternative to improve the assessment of Hg (d) and MeHg (d) concentrations in surface freshwaters by integrating their temporal variability. An original sampling strategy was designed to assess the relevance of 3-mercaptopropyl DGT (Diffusive Gradient in Thin films) to integrate in situ the temporal variations of labile Hg (Hg (DGT) ) and MeHg (MeHg (DGT) ) concentrations. This strategy was implemented on two rivers to study the dynamics of Hg (d) , Hg (DGT) , MeHg (d) and MeHg (DGT) at diurnal and annual timescales. We evidenced that Hg (DGT) and MeHg (DGT) concentrations were generally consistent with discrete sampling measurements of Hg (d) and MeHg (d) in dynamic surface freshwaters. However, Hg (DGT) concentrations were overestimated (2-16 times higher) in case of low flow or low water depth, low suspended particulate matter (SPM) concentrations and elevated daily photoperiod. The most probable hypothesis is that such conditions promoted Hg 0 production, and resulted in Hg 0 uptake by DGT. Thus, attention should be paid when interpreting Hg (DGT) concentrations in surface freshwaters in environmental conditions that could promote Hg 0 production., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Anthropogenic metal contamination results in long-term environmental selective pressure with unclear impacts on bacterial communities, which comprise key players in ecosystem functioning. Since metal contamination poses serious toxicity and bioaccumulation issues, assessing their impact on environmental microbiomes is important to respond to current environmental and health issues. Despite elevated metal concentrations, the river sedimentary microbiome near the MetalEurop foundry (France) shows unexpected higher diversity compared with the upstream control site. In this work, a follow-up of the microbial community assembly during a metal contamination event was performed in microcosms with periodic renewal of the supernatant river water. Sediments of the control site were gradually exposed to a mixture of metals (Cd, Cu, Pb and Zn) in order to reach similar concentrations to MetalEurop sediments. Illumina sequencing of 16S rRNA gene amplicons was performed. Metal-resistant genes, czcA and pbrA, as well as IncP plasmid content, were assessed by quantitative PCR. The outcomes of this study support previous in situ observations showing that metals act as community assembly managers, increasing diversity. This work revealed progressive adaptation of the sediment microbiome through the selection of different metal-resistant mechanisms and cross-species interactions involving public good-providing bacteria co-occurring with the rest of the community., (© FEMS 2020.)

After the exploitation of coal mines in the 19th and 20th centuries in northern France, many mining slag heaps (SH) were left without any particular management or monitoring. Currently, the influence of these SHs on the quality of surrounding wetlands is hardly known. The purpose of this work is to determine the water quality in the neighbourhood of two SHs located near the city of Douai and its influence on the distribution of aquatic invertebrates in local wetlands. Our approach involves (1) the spatial and temporal characterization of the water composition (anions, major elements, sulphide, DOC and alkalinity) and of the biological diversity (aquatic invertebrates) and (2), based on this chemical and biological screening, the establishment of relationships between water quality and biodiversity distribution through multivariate data analysis. The results clearly indicate that substantial leaching from the slag heaps occurs, given the very high concentrations of dissolved sulphates (in the range of 2 g L -1 ). While the pH remains weakly basic, indicating that the leaching water has been neutralized by the highly carbonated regional substratum, high levels of biodegradable organic matter and sulphate contents have been noticed. They sporadically cause significant drops in dissolved oxygen and the occurrence of dissolved sulphides that massively reduce biodiversity, qualitatively and quantitatively. In Summer, oxygen saturation is generally lower due to the higher rate of organic matter degradation, and the risk of anoxic episodes therefore increases. Finally, as wetlands are vulnerable environments, these preliminary results suggest that monitoring and management of these sites must be attempted quickly to avoid the degradation of those valuable habitats., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Most trace metals exhibit a dual role in marine waters, acting as nutrients at low concentration and being toxic at high concentration. But besides concentration range, speciation is also an important factor. They both show both seasonal and spatial variations. A thorough comparison between total dissolved and particulate concentrations estimated from manual sampling and an assessment of the bioavailability using Diffusive Gradients in Thin Films (DGT) has been performed in this work for Cd, Co, Cu, Ni and Pb, at several sampling points of the Belgian Coastal Zone (BCZ). Additional information to trace back the origin and identify the anthropogenic fingerprint of Suspended Particulate Matter (SPM) was measured using stable carbon isotope measurements in particulate organic matter. Our results show that: (i) particulate and total dissolved metal concentrations are higher at two stations, one in the harbor of Oostende and one offshore; (ii) dissolved and particulate trace metal concentrations do not correlate with the dissolved labile fractions; and (iii) SPM in the harbor zone is likely from allochthonous sources, while in the offshore station marine origin has been evidenced. Our results indicate that, even though contamination is higher in the harbor zones, the trace metal toxicity, which is linked to the metal bioavailability, is most likely not higher than in the open sea. However, with increasing acidification of the ocean, a shift from particulate to dissolved phase might lead to increasing adverse effects on the coastal environment., (Copyright © 2019. Published by Elsevier B.V.)

The performances of five Diffusive Gradients in Thin Films (DGT) binding gels, namely 3-mercapto-functionalized silica (3MP), ferrihydrite (Fh), Metsorb ® , zinc ferrite (ZnFe 2 O 4 ) , and Zirconium oxide (ZrO 2 ) , were evaluated for in situ determination of As speciation in water and sediments. A combination of batch experiments at various pH (without addition of buffers) and in the presence of reduced species (Mn 2+ , Fe 2+ and HS - ),time-series experiments in oxic waters, and in situ deployment in anoxic river sediments has permitted to evaluate the potential interferences among the binding gels. Firstly, the efficiency of each DGT binding gel dedicated to total As (i.e., Fh, Metsorb®, ZnFe 2 O 4 and ZrO 2 ) or As(III) (i.e., 3MP) determination confirms that the determination of As species is possible in oxic freshwater and seawater over 96 h for a wide range of pH (5-9). Secondly, concerning the deployment in river sediment, high HCO 3 - concentrations have a little negative effect only on the DGT performances of the iron(III)-binding gels (i.e, Fh and ZnFe 2 O 4 ). Thirdly, the presence of sulfides does not show any effect on the DGT uptake of As, but strongly affects the elution factor parameter. Discrepancies in elution between the different binding gels potentially result in precipitation of orpiment, especially in 1 mol L -1 HNO 3 . A correction of the classical elution factor derived from batch experiments was applied to provide more representative results. Finally, this study shows the difficulties to determine As speciation in anoxic sediments, and suggests that corrections of the elution factor may be required as a function of the species present in the deployment matrices., (Copyright © 2019 Elsevier B.V. All rights reserved.)

The aim of this paper is to better understand the functioning of the River Selle (northern France) during dry weather and storm events, to assess the impact of a town on the surface water quality and to suggest qualitative assumptions on the vulnerability of water quality to weather conditions. Two high-frequency monitoring stations covering the Cateau-Cambrésis town were deployed during 4 months in 2016. River flow, water temperature, pH, dissolved oxygen, turbidity, conductivity, total organic carbon, nitrates and phosphates were monitored every 10 min. The water supply of the River Selle is mainly dominated by groundwater as shown by the behaviour of the river flow, the water temperature and the nitrate concentrations in both surface water and groundwater. The reference station located at the upstream of the river (Saint Souplet) exhibits low anthropogenic pressure during dry weather but is significantly impacted during storm events. At the downstream of the Cateau-Cambrésis town, the water quality is severely impacted by phosphates during dry weather mainly due to wastewater inputs into the river. An additional load of pollution is highlighted during storm events. According to our results, the water quality of the River Selle would degrade if actions to reduce dry-weather and storm events pollution sources are not undertaken rapidly. Moreover, nutrients, particularly phosphates, are clearly in excess in this system. Efforts to combat soil leaching and the revision of sewage systems and urban wastewater treatment in the catchment are two key points to tackle. Finally, this study shows the importance of understanding the current behaviour of a given river towards dry weather and storm events before suggesting local scenarios of the impact of climate change on surface water quality., (Copyright © 2018 Elsevier B.V. All rights reserved.)

During the last few decades, stormwater ponds have become an alternative management practice in order to avoid flooding and to contain rainwater and runoff in urban areas where impervious land cover has increased. A second purpose of stormwater ponds is to improve the quality of runoff water that is usually contaminated with nitrogen, phosphorus, metals and organic micropollutants. Processes used are based on natural methods such as settlement and contribute to minimize the impact of these inputs to the natural aquatic system. This study aims to better understand the behavior of a wet stormwater pond, Heron Lake (33 ha) located in the city of Villeneuve d'Ascq in northern France through various indicators [trace metals, PAHs, PCBs, caffeine (CAF), carbamazepine (CBZ), nutrients and pathogens]. For that purpose, water quality was monitored for 1 year, mainly at the entrance and at the outlet of the lake. Sampling have also been done in the downstream aquatic environment, the Marque River. Sediments were sampled in the lake to evaluate the pollution trapped during sedimentation. Our results of both water and sediment sampling highlight: (i) the wastewater input into the Heron Lake is estimated to be equivalent to that of roughly 3800 inhabitants; (ii) the removal rates observed at the outlet, relative to concentrations at the entrance channel, vary as follows for these dissolved species: 24% for NO 3 - and PO 4 3- , 28% for CBZ, 35% for Cu, 63% for Pb, 78% for CAF, 84% for Zn and up to 93% for NH 4 + ; (iii) there are high levels of sediment contamination with metals, PAHs and PCBs at the entrance channel; (iv) the eutrophication of this pond is attributed to persistent high nutrient concentrations in both water and sediment, and has contributed to the development of an invasive macrophyte, the Elodea nuttallii; and (v) there appears to be only a negligible impact of the discharge from the lake to the natural watercourse, contributing annual loads of <2 up to 6% of the total amount of Cu, Pb, Zn, CAF, CBZ and nutrients measured in the Marque River, and having a slight diluting effect on concentrations in the Marque River., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Electrolabile reduced manganese (II) has been monitored by voltammetry during two periods of one month in summer 2014 and at the end of winter 2015 in a small river (the Marque River) located in northern France and going through a suburban area with agricultural activities. Diel variations, evolution within the one-month periods and seasonal differences have been observed. Taking into consideration the multiple physical, biological and chemical reactions regulating manganese speciation in aquatic systems, it has been demonstrated that manganese speciation is probably controlled by the competition of two antagonist reactions: the photoreduction of manganese oxides (in broad sense and represented thereafter by MnOx) and the biotic oxidation of Mn(II). Depending on the season, the biological activity in the river and the amount of luminosity reaching the MnOx, either the production of reduced labile Mn(II) or the precipitation of MnOx can become the dominant process. Other punctual events such as the drop of oxygen concentration due to large inputs of biodegradable organic matter and eutrophication phenomena, rainy events and high luminosity periods can also affect the behaviour of dissolved Mn(II) in the Marque River and so, of other contaminants., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Human activities on the shoreline generate a growing pollution, creating deleterious habitats in coastal zones. Some species nevertheless succeed in such harsh milieus, raising the question of their tolerance to environmental stress. The annelid Hediste diversicolor lives buried in the sediments, directly exposed to contaminants trapped in the mud. After verifying the similarity of their genetic contexts, we compared reproductive output and individual immune resistance measures of populations living in polluted vs. 'clean' sediments, and related these assessments with measures of phthalates and metal pollution, and associated toxicity indices. Chemical analyses predicted no toxicity to the local infauna, and phenological studies evidenced no direct cost of living in noxious habitats. However, populations exposed to pollutants showed a significantly reduced survival upon infection with a local pathogen. Surprisingly, physiological studies evidenced a basal overinflammatory state in the most exposed populations. This over-activated baseline immune phenotype likely generates self-damage leading to enhanced immune cell death rate and immune failure. Monitoring the immune status of individual worms living in anthropic areas could thus be used as a reliable source of information regarding the actual health of wild populations., (Copyright © 2017 Elsevier B.V. All rights reserved.)

The relevance of Polar Organic Chemical Integrative Samplers (POCIS) was evaluated for the assessment of concentrations of 46 pesticides and 19 pharmaceuticals in a small, peri-urban river with multi-origin inputs. Throughout the period of POCIS deployment, 24h-average water samples were collected automatically, and showed the rapid temporal evolution of concentrations of several micropollutants, as well as permitting the calculation of average concentrations in the water phase for comparison with those estimated from POCIS passive samplers. In the daily water samples, cyproconazol, epoxyconazol and imidacloprid showed high temporal variations with concentrations ranging from under the limit of detection up to several hundreds of ngL -1 . Erythromycin, cyprofloxacin and iopromide also increased rapidly up to tens of ngL -1 within a few days. Conversely, atrazine, caffeine, diclofenac, and to a lesser extent carbamazepine and sucralose, were systematically present in the water samples and showed limited variation in concentrations. For most of the substances studied here, the passive samplers gave reliable average concentrations between the minimal and maximal daily concentrations during the time of deployment. For pesticides, a relatively good correlation was clearly established (R 2 =0.89) between the concentrations obtained by POCIS and those gained from average water samples. A slight underestimation of the concentration by POCIS can be attributed to inappropriate sampling rates extracted from the literature and for our system, and new values are proposed. Considering the all data set, 75% of the results indicate a relatively good agreement between the POCIS and the average water samples concentration (values of the ratio ranging between 0,33 and 3). Note further that this agreement between these concentrations remains valid considering different sampling rates extracted from the literature., (Copyright © 2017 Elsevier B.V. All rights reserved.)

A new method based on passive samplers has been developed to assess the diffusive flux of fluorene, fluoranthene and pyrene in the sediment bed and across the sediment-water interface. The dissolved compound concentration gradient in the sediment in the vertical direction was measured at the outlet of a storm water pond by using polyethylene strips as passive samplers. Simultaneously, the dissipation of a set of tracer compounds preloaded in the passive samplers was measured to estimate the effective diffusion coefficients of the pollutants in the sediment. Both measurements were used to evaluate the diffusive flux of the compounds according to Fick's first law. The diffusive fluxes of the 3 studied compounds have been estimated with a centimetre-scale resolution in the upper 44cm of the sediment. According to the higher compound diffusion coefficient and the steeper concentration gradient in the surficial sediment layer, the results show that the net flux of compounds near the sediment interface (1cm depth) is on average 500 times higher than in the deep sediment, with average fluxes at 1cm depth on the order of 5, 0.1 and 0.1ng/m 2 /y for fluorene, fluoranthene and pyrene, respectively., (Copyright © 2016 Elsevier B.V. All rights reserved.)