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Polyvinylpyrrolidone (PVP) fibers with cobalt ferrite nanoparticles (CoFe2O4) were prepared by an electrospinning technique to study the electrical resistance and magnetic properties of the nanocomposite. The samples were characterized using Fourier transform infrared spectroscopy (FTIR), Raman spectroscopy, transmission electron microscopy (TEM), and thermogravimetric analysis (TGA). Magnetic properties were measured using vibrating sample magnetometry (VSM). PVP fibers showed an average diameter of 3.74μm with a resistance of 121.58 GΩ and 2.22μm and 1.20 GΩ with the incorporation of CoFe2O4 nanoparticles. Cobalt ferrite nanoparticles have a maximum magnetization of 81.9 emu/g, and the CoFe2O4/PVP fibers present a diamagnetic behavior with a maximum magnetization of 0.07 emu/g. Combining the versatility of PVP as a polymer matrix with the magnetic and electric properties of cobalt ferrite nanoparticles, this nanocomposite may open up new potential applications for developing electrically conductive novel nanomaterials and devices.

Magnetic carbon nanotubes (MagCNTs) have attracted significant interest due to their exceptional magnetic properties, robust adsorption capabilities, and unique thermal conductivity, making them valuable in fields such as drug delivery and environmental technology. However, their production and design face challenges due to complex methodologies and the exposure of magnetic nanoparticles (NPs) to the environment, which hinders scalability and compromises their applications. Issues like rapid oxidation of iron-based NPs and potential toxicity of alternative metals like cobalt or nickel further limit their efficacy and utility. To address these challenges, encapsulating the metallic NPs can preserve their magnetic properties and enhance application options. In this study, we introduce a novel, in-situ, one-step synthesis method to encapsulate magnetic NPs, such as Fe3O4, Fe, and Fe3C, within the structure of carbon nanotubes (CNTs). The material was synthesized via Chemical Vapor Deposition (CVD) using Fe3O4 NPs as the catalyst. The composition and morphology were studied using High Resolution Transmission Electron Microscopy (HRTEM), Energy Dispersive X-ray Spectroscopy (EDS), Raman spectroscopy, X-ray Diffraction (XRD), X-ray Photoelectron Spectroscopy (XPS), Thermogravimetric Analysis (TGA), and vibrating sample magnetometry (VSM). These analysis revealed the effective confinement of magnetic NPs, with size approximately 10–20 nm, within the CNTs. Furthermore, VSM results confirmed the magnetic properties at room temperature, with a magnetic saturation value of 35.8 emu/g. This approach offers a refined production process and material design, expanding their applicability in various technological and biomedical fields.

Abstract Background Floodplains are biodiversity hotspots and provide numerous ecosystem services. In recent decades, however, 70–90% of Europe’s floodplains have been structurally degraded. Accordingly, many (inter-)national programs aim to restore and protect floodplain ecosystems. The success of such measures also depends on the chemical contamination, especially of floodplain soils and sediments, which serve as sinks and sources for a variety of pollutants. In this study, we assess the current ecotoxicological status of a floodplain restoration site along the Main River (Frankfurt am Main, Germany) and estimate its development potential with respect to the influence of a local industrial plant and potential legacy contaminations. We therefore use in vitro effect-based methods (EBMs) testing for baseline toxicity, mutagenicity, dioxin-like and estrogenic activities, coupled with chemical analysis. Results Of all water bodies analyzed, the overall toxicity was highest in two flood depressions. In the respective water phase, estrogenic activities exceeded the environmental quality standard and sediment samples were positive for all tested endpoints. Chemical analysis of these sediments revealed high concentrations of polycyclic aromatic hydrocarbons. Soil samples from frequently flooded areas showed the highest mutagenic potential for both frameshift and point mutations with and without metabolic activation. The industrial effluent showed baseline toxic, mutagenic, and dioxin-like activities, that were highly diluted in the Main River. In turn, most of the sediment samples downstream of the industrial discharge showed significantly elevated baseline toxic, estrogenic and dioxin-like activities as well as increased chemical contamination. Conclusion Based on the results of this study, we rate the overall ecotoxicological status of a recently established tributary and groundwater-fed ponds as good, and identified two flood depressions near the Main River as hot spots of contamination. We assume that the observed mutagenicity in the floodplain soils is related to legacy contaminations from former aniline and azo dye production. In terms of the development potential of the floodplain restoration site, we emphasize considering the remobilization of pollutants from these soils and suppose that, in the long term, pollution of the Main River and the local industrial plant may negatively impact sediment quality in its tributaries. With this study, we confirmed the utility of in vitro EBMs for identifying chemically and ecotoxicologically relevant sites.

Addressing global change requires standardised observations across all ecosystem spheres. To that end, the distributed Integrated European Long-Term Ecosystem, critical zone and socio-ecological Research Infrastructure (eLTER RI) strives for an optimal observational design of its over 200 in-situ facilities. Their spatial distribution should be unbiased to scale local data to its continental target region.Therefore, we assessed biases in the emerging eLTER RI in-situ facility network. We (i) conducted a survey describing the emerging eLTER RI, (ii) detected critical gaps in its coverage of Reference Parameters by identifying biases in a six-dimensional thematic space and determined regions, where these biases cluster spatially, and (iii) derived recommendations to further develop the eLTER RI network.Three distinct gaps were identified: the Iberian, Eastern and Nordic Gap. They resulted mainly from underrepresentation of agricultural lands, mesic and dry regions with low economic density and the Mediterranean, Continental and Boreal biogeoregions. The patterns of underrepresentation are driven by various factors including the thematic context of site establishment over the past decades, operations logistics and funding constraints. We consider closing these gaps of highest priority for spatial network development.Mitigating the biases in the eLTER RI network is crucial to enable confident scaling of local data to the European scale. This will allow the eLTER RI to provide a comprehensive foundation for scientists, policy and decision makers to face global change. Next, a comprehensive dataset of possible additional research sites over Europe must be analysed to derive site- and country-specific recommendations for cost-efficient gap mitigation.

Human exposure to pesticides in the general population occurs mainly through food consumption. However, specific dietary habits or food products that contribute to pesticide exposure are often unknown. In this study, we propose a combined screening for polyphenols and pesticide residues by liquid chromatography coupled to high-resolution mass spectrometry (LC-HRMS) to assess the diet and the associated pesticide exposure. We measured 587 urine samples from women around the 34th week of pregnancy of a prospective mother–child cohort. A non-targeted screening for flavonoid-like compounds related to fruit and vegetable consumption was performed, prioritizing 164 features and identifying a total of 46 features by spectral library search. Based on a subset of markers, k-means clustering was performed, leading to four clusters with presumably similar dietary habits. The clusters were compared against food questionnaire data collected within the period of sample collection. Suspect screening of more than 500 pesticide residues including metabolites was performed, with a total of 40 residues being reported for 27 different pesticides. The detection of pesticide residues was compared across the different clusters of dietary habits. Indications were found that pyrimethanil metabolites might be associated with the consumption of citrus fruits or derivate products. We demonstrate that the method used has the potential to reveal patterns of pesticide intake from specific food commodities.

Synthetic organic chemicals, including pesticides, pharmaceuticals, and industrial compounds, pose a growing threat to marine ecosystems. Despite their potential impact, data on the co-occurrence of these contaminants in multiple compartments, including surface water, bottom water, porewater, and sediment in the marine environment remains limited. Such information is critical for assessing coastal chemical status, establishing environmental quality benchmarks, and conducting comprehensive environmental risk assessments. In this study, we describe a multifaceted monitoring campaign targeting pesticides, pharmaceuticals, surfactants, additives, and plasticizers among other synthetic chemicals in four sampling sites. One site was located in the small Coliumo bay affected by urban settlements and tourism in central-south and additionally, we sampled three sites, Caucahue Channel, affected by urban settlements and salmon farming in northern Patagonia in Chile. Surface water, bottom water, porewater, and adjacent sediment samples were collected for target screening analysis in LC- and GC-HRMS platforms. Our results show the detection of up to 83 chemicals in surface water, 71 in bottom water, 101 in porewater, and 244 in sediments. To enhance data utility and reuse potential, we provide valuable information on the mode of action and molecular targets of the identified chemicals. This comprehensive dataset contributes to defining pollution fingerprints in coastal areas of the Global South, including remote regions in Patagonia. It serves as a critical resource for future research including marine chemical risk assessment, policymaking, and the advancement of environmental protection in these regions.

Abstract Background Many aquatic insects emerge as adults from water bodies to complete parts of their life cycle in terrestrial ecosystems and are potential prey for riparian predators. The benefits of riparian predators from aquatic insects include higher contents of long-chain polyunsaturated fatty acids (PUFA) compared to terrestrial insects. Aquatic insects are therefore considered a high-quality food. Food containing high levels of PUFA can enhance growth and immune response of spiders. However, agricultural stressors like nutrient increase, pesticides and habitat degradation can affect the biomass of aquatic insects and in turn the diet of spiders. Studies quantifying the influence of land use on fatty acid (FA) profiles of emergent aquatic insects and riparian predators are lacking. We quantified differences in exports of FA, saturated FA, monounsaturated FA, and PUFA, FA profiles of aquatic insects and spiders between forested and agricultural sites over the primary emergence period within one year. The FA export to the riparian food web is crucial to understand energy fluxes between ecosystems. Furthermore, we monitored environmental variables to identify associations between agricultural stressors and FA profiles of aquatic insects and spiders. Results We found differences in FA export and profiles of aquatic insects between land-use types. The quantity of total FA export via aquatic insects was lower in agricultural sites (95% CI 1147–1313 µg m−2) in comparison to forested sites (95% CI 1555–1845 µg m−2), while the biomass export was higher in agricultural sites. Additionally, in spring the PUFA export was significantly lower (up to 0.06 µg d−1 m−2) in agricultural than forested sites. Agricultural stressors explained only little variation in the FA profiles of aquatic insects, e.g., 4% for caddisflies and 12% for non-biting midges. Percentage of shading and pool habitats were identified as most important variables explaining the variation in FA profiles. Conclusion The quality of aquatic insects as food source for riparian spiders was smaller in agricultural than forested sites, which can decrease the fitness of riparian predators. To improve our capacity to predict potential adverse effects in the riparian food web, future studies should identify the mechanisms underlying a lower PUFA content.

Chemical pollution of the aquatic environment is nowadays characterised by increasing levels of anthropogenic organic compounds at low concentrations and is recognised as one of the main drivers of the deteriorated ecological state of European waterbodies. To improve the understanding of the impact of chemical pollution in surface waters, a combined approach of chemical and bioanalytical testing is considered necessary for effective ecologically oriented water management. For this dataset, six 25-L water samples were collected at six sampling sites along the Holtemme River in Central Germany using large-volume solid phase extraction. All samples were analysed by targeted high-resolution liquid chromatography–mass spectrometry (LC–MS) and a selected bioanalytical test battery using effect-based methods. These methods included cytotoxicity assessment, several mechanism-specific CALUXⓇ tests to identify endocrine and oxidative stress-related effects and the fish embryo acute toxicity test to investigate (sub)lethal effects in the model species Danio rerio. This approach provided a dataset that offers a longitudinal characterisation of the chemical pollution and ecotoxicological impacts. The combination of chemical analysis and effect-based analysis is valuable for future studies as it will help researchers, risk assessors and authorities to identify hot spots of chemical pollution, monitor environmental quality standards and recommend mitigation strategies.

Introduction Compulsory admissions are associated with feelings of fear, humiliation and powerlessness. The number of compulsory admissions in Germany and other high-income countries has increased in recent years. Peer support has been shown to increase the self-efficacy of individuals with mental health conditions in acute crises and to reduce the use of coercive measures in clinical settings. The objective of this study is to reduce the number of compulsory admissions by involving peer support workers (PSWs) in acute mental health crises in outreach and outpatient settings.Methods and analysis This one-year intervention is an exploratory, cluster randomised study. Trained PSWs will join the public crisis intervention services (CIS) in two of five regions (the intervention regions) in the city of Bremen (Germany). PSWs will participate in crisis interventions and aspects of the mental health services. They will be involved in developing and conducting an antistigma training for police officers. The remaining three regions will serve as control regions. All individuals aged 18 and older who experience an acute mental health crisis during the operating hours of the regional CIS in the city of Bremen (around 2000 in previous years) will be included in the study. Semistructured interviews will be conducted with PSWs, 30 patients from control and intervention regions, as well as two focus group discussions with CIS staff. A descriptive comparison between all participants in the intervention and control regions will assess the proportion of compulsory admissions in crisis interventions during the baseline and intervention years, including an analysis of temporal changes.Ethics and dissemination This study was approved by the Ethics Committee of the University of Bremen (file 2022-09) on 20 June 2022. The results will be presented via scientific conferences, scientific journals and communicated to policy-makers and practitioners.Trial registration number DRKS00029377.

The chemical burden on the environment and human population is increasing. Consequently, regulatory risk assessment must keep pace to manage, reduce, and prevent adverse impacts on human and environmental health associated with hazardous chemicals. Surveillance of chemicals of known, emerging, or potential future concern, entering the environment-food-human continuum is needed to document the reality of risks posed by chemicals on ecosystem and human health from a one health perspective, feed into early warning systems and support public policies for exposure mitigation provisions and safe and sustainable by design strategies. The use of less-conventional sampling strategies and integration of full-scan, high-resolution mass spectrometry and effect-directed analysis in environmental and human monitoring programmes have the potential to enhance the screening and identification of a wider range of chemicals of known, emerging or potential future concern. Here, we outline the key needs and recommendations identified within the European Partnership for Assessment of Risks from Chemicals (PARC) project for leveraging these innovative methodologies to support the development of next-generation chemical risk assessment.

There is increasing awareness that chemical pollution of freshwater systems with complex mixtures of chemicals from domestic sources, agriculture and industry may cause a substantial chemical footprint on water organisms, pushing aquatic ecosystems outside the safe operating space. The present study defines chemical footprints as the risk that chemicals or chemical mixtures will have adverse effects on a specific group of organisms. The aim is to characterise these chemical footprints in European streams based on a unique and uniform screening of more than 600 chemicals in 445 surface water samples, and to derive site- and compound-specific information for management prioritisation purposes. In total, 504 pesticides, biocides, pharmaceuticals and other compounds have been detected, including frequently occurring and site-specific compounds with concentrations up to 74 µg/L. Key finding is that three-quarter of the investigated sites in 22 European river basins exceed established thresholds for chemical footprints in freshwater, leading to expected acute or chronic impacts on aquatic organisms. The largest footprints were recorded on invertebrates, followed by algae and fish. More than 70 chemicals exceed thresholds of chronic impacts on invertebrates. For all organism groups, pesticides and biocides were the main drivers of chemical footprints, while mixture impacts were particularly relevant for invertebrates. No clear significant correlation was found between chemical footprints and the urban discharge fractions, suggesting that effluent-specific quality rather than the total load of treated wastewater in the aquatic environment and the contribution of diffuse sources, e.g. from agriculture, determine chemical footprints.

Abstract Introduction Hip and knee osteoarthritis are associated with functional limitations, pain and restrictions in quality of life and the ability to work. Furthermore, with growing prevalence, osteoarthritis is increasingly causing (in)direct costs. Guidelines recommend exercise therapy and education as primary treatment strategies. Available options for treatment based on physical activity promotion and lifestyle change are often insufficiently provided and used. In addition, the quality of current exercise programmes often does not meet the changing care needs of older people with comorbidities and exercise adherence is a challenge beyond personal physiotherapy. The main objective of this study is to investigate the short- and long-term (cost-)effectiveness of the SmArt-E programme in people with hip and/or knee osteoarthritis in terms of pain and physical functioning compared to usual care. Methods This study is designed as a multicentre randomized controlled trial with a target sample size of 330 patients. The intervention is based on the e-Exercise intervention from the Netherlands, consists of a training and education programme and is conducted as a blended care intervention over 12 months. We use an app to support independent training and the development of self-management skills. The primary and secondary hypotheses are that participants in the SmArt-E intervention will have less pain (numerical rating scale) and better physical functioning (Hip Disability and Osteoarthritis Outcome Score, Knee Injury and Osteoarthritis Outcome Score) compared to participants in the usual care group after 12 and 3 months. Other secondary outcomes are based on domains of the Osteoarthritis Research Society International (OARSI). The study will be accompanied by a process evaluation. Discussion After a positive evaluation, SmArt-E can be offered in usual care, flexibly addressing different care situations. The desired sustainability and the support of the participants’ behavioural change are initiated via the app through audio-visual contact with their physiotherapists. Furthermore, the app supports the repetition and consolidation of learned training and educational content. For people with osteoarthritis, the new form of care with proven effectiveness can lead to a reduction in underuse and misuse of care as well as contribute to a reduction in (in)direct costs. Trial registration German Clinical Trials Register, DRKS00028477. Registered on August 10, 2022.

Abstract Background Chemical pollution forms a severe threat for human and environmental health. While the risks for European lowland water bodies are well known, there is little knowledge on remote aquatic ecosystems and particularly mountain lakes, despite their importance for the provision of freshwater. Here, we critically review the current knowledge on the exposure and risk by chemical pollution for mountain lakes and present a tiered approach on how to advance effectively our understanding in the future. Results Generally, pollutant monitoring data are currently incomplete, with many regions and substances having been only poorly investigated. More reliable data exist only for persistent organic pollutants (POPs). However, there is increasing evidence that even remote mountain lakes are exposed to a wide range of organic pollutants. Among them potent pesticides currently used in agricultural and biocidal applications, such as diazinon and permethrin. The exposure of mountain lakes to pollutants follows a complex pattern. Pollutants are introduced into mountain lakes via the atmospheric deposition and run-off from the watershed, but also local sources, like tourism and pastoralism. Our risk assessment and recent biomonitoring studies suggest that there are widespread chronic toxic risks on crustacean in mountain ranges. If mountain ranges are exposed to tourism and pastoralism, even acute toxic effects on crustacean are possible. Thereby, the vulnerability of mountain lakes to toxic effects has to be expected to be particularly high due to the harsh environmental conditions at high altitudes, the organism’s traits, the insular position of mountain lakes and a lower species richness with increasing altitudes. Furthermore, there is little knowledge on the biological processes leading to the degradation of chemical pollutants under the environmental and ecological conditions of mountain ecosystems. Conclusion While the exposure and sensitivity of mountain aquatic ecosystems is currently poorly investigated, the existing data suggest that it is very likely that also water bodies as remote as mountain lakes do suffer from pollution-induced toxicity. To verify this suggestion and expand the existing knowledge, it is necessary that future studies combine a more holistic pollution monitoring with exposure modelling and links to biological effects. Only then will it be possible to obtain a more reliable understanding of the impact of chemical pollution on aquatic mountain ecosystems and to protect these fragile ecosystems.

Background: Allergenic proteins can cause IgE-mediated adverse reactions in sensitized individuals. Although the sequences of many allergenic proteins have been identified, bioinformatics data analysis with advanced computational methods and modeling is needed to identify the basis for IgE binding and cross-reactivity. Objective: We aim to present the features and use of the updated Structural Database of Allergenic Proteins 2.0 (SDAP 2.0) webserver, a unique, publicly available resource to compare allergens using specially designed computational tools and new high-quality 3-D models for most known allergens. Methods: Previously developed and novel software tools for identifying cross-reactive allergens using sequence and structure similarity are implemented in SDAP 2.0. A comprehensive set of high-quality 3-D models of most allergens was generated with the state-of-the-art AlphaFold 2 software. A graphics tool enables the interactive visualization of IgE epitopes on experimentally determined and modeled 3-D structures. Results: A user can search for allergens similar to a given input sequence with the FASTA algorithm or the window-based World Health Organization/International Union of Immunological Societies (WHO/IUIS) guidelines on safety concerns of novel food products. Peptides similar to known IgE epitopes can be identified with the property distance tool and conformational epitopes by the Cross-React method. The updated database contains 1657 manually curated sequences including all allergens from the IUIS database, 334 experimentally determined X-ray or NMR structures, and 1565 3-D models. Each allergen/isoallergen is classified according to its protein family. Conclusions: SDAP provides access to the steadily increasing information on allergenic structures and epitopes with integrated bioinformatics tools to identify and analyze their similarities. In addition to serving the research and regulatory community, it provides clinicians with tools to identify potential coallergies in a sensitive patient and can help companies to design hypoallergenic foods and immunotherapies.

Chemical pollution caused by synthetic organic chemicals at low concentrations in the environment poses a growing threat to the ecological status of aquatic ecosystems. These chemicals are regularly released into surface waters through both treated and untreated effluents from wastewater treatment plants (WWTPs), agricultural runoff, and industrial discharges. Consequently, they accumulate in surface waters, distribute amongst environmental compartments according to their physicochemical properties, and cause adverse effects on aquatic organisms. Unfortunately, there is a lack of data regarding the occurrence of synthetic organic chemicals, henceforth micropollutants, in South American freshwater ecosystems, especially in Chile.To address this research gap, we present a comprehensive dataset comprising concentrations of 153 emerging chemicals, including pesticides, pharmaceutical and personal care products (PPCPs), surfactants, and industrial chemicals. These chemicals were found to co-occur in surface waters within Central Chile, specifically in the River Aconcagua Basin. Our sampling strategy involved collecting surface water samples from streams and rivers with diverse land uses, such as agriculture, urban areas, and natural reserves. For sample extraction, we employed an on-site large-volume solid phase extraction (LVSPE) device. The resulting environmental extracts were then subjected to wide-scope chemical target screening using gas chromatography and liquid chromatography high-resolution mass spectrometry (GC- and LCHRMS).The dataset we present holds significant value in assessing the chemical status of water bodies. It enables comparative analysis of pollution fingerprints associated with emerging chemicals across different freshwater systems. Moreover, the data can be reused for environmental risk assessment studies. Its utilisation will contribute to a better understanding of the impact and extent of chemical pollution in aquatic ecosystems, facilitating the development of effective mitigation strategies.

Aquatic environments are polluted with a multitude of organic micropollutants, which challenges risk assessment due the complexity and diversity of pollutant mixtures. The recognition that certain source-specific background pollution occurs ubiquitously in the aquatic environment might be one way forward to approach mixture risk assessment. To investigate this hypothesis, we prepared one typical and representative WWTP effluent mixture of organic micropollutants (EWERBmix) comprised of 81 compounds selected according to their high frequency of occurrence and toxic potential. Toxicological relevant effects of this reference mixture were measured in eight organism- and cell-based bioassays and compared with predicted mixture effects, which were calculated based on effect data of single chemicals retrieved from literature or different databases, and via quantitative structure-activity relationships (QSARs). The results show that the EWERBmix supports the identification of substances which should be considered in future monitoring efforts. It provides measures to estimate wastewater background concentrations in rivers under consideration of respective dilution factors, and to assess the extent of mixture risks to be expected from European WWTP effluents. The EWERBmix presents a reasonable proxy for regulatory authorities to develop and implement assessment approaches and regulatory measures to address mixture risks. The highlighted data gaps should be considered for prioritization of effect testing of most prevalent and relevant individual organic micropollutants of WWTP effluent background pollution. The here provided approach and EWERBmix are available for authorities and scientists for further investigations. The approach presented can furthermore serve as a roadmap guiding the development of archetypic background mixtures for other sources, geographical settings and chemical compounds, e.g. inorganic pollutants.

Monitoring methodologies reflecting the long-term quality and contamination of surface waters are needed to obtain a representative picture of pollution and identify risk drivers. This study sets a baseline for characterizing chemical pollution in the Danube River using an innovative approach, combining continuous three-months use of passive sampling technology with comprehensive chemical (747 chemicals) and bioanalytical (seven in vitro bioassays) assessment during the Joint Danube Survey (JDS4). This is one of the world's largest investigative surface-water monitoring efforts in the longest river in the European Union, which water after riverbank filtration is broadly used for drinking water production. Two types of passive samplers, silicone rubber (SR) sheets for hydrophobic compounds and AttractSPETM HLB disks for hydrophilic compounds, were deployed at nine sites for approximately 100 days. The Danube River pollution was dominated by industrial compounds in SR samplers and by industrial compounds together with pharmaceuticals and personal care products in HLB samplers. Comparison of the Estimated Environmental Concentrations with Predicted No-Effect Concentrations revealed that at the studied sites, at least one (SR) and 4–7 (HLB) compound(s) exceeded the risk quotient of 1. We also detected AhR-mediated activity, oxidative stress response, peroxisome proliferator-activated receptor gamma-mediated activity, estrogenic, androgenic, and anti-androgenic activities using in vitro bioassays. A significant portion of the AhR-mediated and estrogenic activities could be explained by detected analytes at several sites, while for the other bioassays and other sites, much of the activity remained unexplained. The effect-based trigger values for estrogenic and anti-androgenic activities were exceeded at some sites. The identified drivers of mixture in vitro effects deserve further attention in ecotoxicological and environmental pollution research. This novel approach using long-term passive sampling provides a representative benchmark of pollution and effect potentials of chemical mixtures for future water quality monitoring of the Danube River and other large water bodies.

Abstract Anthropogenic chemicals in freshwater environments contribute majorly to ecosystem degradation and biodiversity decline. In particular anthropogenic organic micropollutants (AOM), a diverse group of compounds, including pesticides, pharmaceuticals, and industrial chemicals, can significantly impact freshwater organisms. AOM were found to impact genetic diversity of freshwater species; however, to which degree AOM cause changes in population genetic structure and allelic richness of freshwater macroinvertebrates remains poorly understood. Here, the impact of AOM on genetic diversity of the common amphipod Gammarus pulex (Linnaeus, 1758) (clade E) was investigated on a regional scale. The site‐specific AOM levels and their toxic potentials were determined in water and G. pulex tissue sample extracts for 34 sites along six rivers in central Germany impacted by wastewater effluents and agricultural run‐off. Population genetic parameters were determined for G. pulex from the sampling sites by genotyping 16 microsatellite loci. Genetic differentiation among G. pulex from the studied rivers was found to be associated with geographic distance between sites and to differences in site‐specific concentrations of AOM. The genetic diversity parameters of G. pulex were found to be related to the site‐specific AOM levels. Allelic richness was significantly negatively correlated with levels of AOM in G. pulex tissue (p

Abstract Background The sample size calculation in a confirmatory diagnostic accuracy study is performed for co-primary endpoints because sensitivity and specificity are considered simultaneously. The initial sample size calculation in an unpaired and paired diagnostic study is based on assumptions about, among others, the prevalence of the disease and, in the paired design, the proportion of discordant test results between the experimental and the comparator test. The choice of the power for the individual endpoints impacts the sample size and overall power. Uncertain assumptions about the nuisance parameters can additionally affect the sample size. Methods We develop an optimal sample size calculation considering co-primary endpoints to avoid an overpowered study in the unpaired and paired design. To adjust assumptions about the nuisance parameters during the study period, we introduce a blinded adaptive design for sample size re-estimation for the unpaired and the paired study design. A simulation study compares the adaptive design to the fixed design. For the paired design, the new approach is compared to an existing approach using an example study. Results Due to blinding, the adaptive design does not inflate type I error rates. The adaptive design reaches the target power and re-estimates nuisance parameters without any relevant bias. Compared to the existing approach, the proposed methods lead to a smaller sample size. Conclusions We recommend the application of the optimal sample size calculation and a blinded adaptive design in a confirmatory diagnostic accuracy study. They compensate inefficiencies of the sample size calculation and support to reach the study aim.

Introduction Individuals with intellectual disabilities (ID) often suffer from hearing loss, in most cases undiagnosed or inappropriately treated. The implementation of a programme of systematic hearing screening, diagnostics, therapy initiation or allocation and long-term monitoring within the living environments of individuals with ID (nurseries, schools, workshops, homes), therefore, seems beneficial.Methods and analysis The study aims to assess the effectiveness and costs of a low-threshold screening programme for individuals with ID. Within this programme 1050 individuals with ID of all ages will undergo hearing screening and an immediate reference diagnosis in their living environment (outreach cohort). The recruitment of participants in the outreach group will take place within 158 institutions, for example, schools, kindergartens and places of living or work. If an individual fails the screening assessment, subsequent full audiometric diagnostics will follow and, if hearing loss is confirmed, initiation of therapy or referral to and monitoring of such therapy. A control cohort of 141 participants will receive an invitation from their health insurance provider via their family for the same procedure but within a clinic (clinical cohort). A second screening measurement will be performed with both cohorts 1 year later and the previous therapy outcome will be checked. It is hypothesised that this programme leads to a relevant reduction in the number of untreated or inadequately treated cases of hearing loss and strengthens the communication skills of the newly or better-treated individuals. Secondary outcomes include the age-dependent prevalence of hearing loss in individuals with ID, the costs associated with this programme, cost of illness before-and-after enrolment and modelling of the programme’s cost-effectiveness compared with regular care.Ethics and dissemination The study has been approved by the Institutional Ethics Review Board of the Medical Association of Westphalia-Lippe and the University of Münster (No. 2020-843 f-S). Participants or guardians will provide written informed consent. Findings will be disseminated through presentations, peer-reviewed journals and conferences.Trial registration number DRKS00024804.

Abstract SARS-CoV-2 has steadily mutated during its spread to > 300 million people throughout the world. The WHO has designated strains with certain mutations, “variants of concern” (VOC), as they may have higher infectivity and/or resist neutralization by antibodies in sera of vaccinated individuals and convalescent patients. Methods to detect regionally emerging VOC are needed to guide treatment and vaccine design. Cluster and network analysis was applied to over 1.2 million sequences of the SARS-CoV-2 spike protein from 36 countries in the GISAID database. While some mutations rapidly spread throughout the world, regionally specific groups of variants were identified. Strains circulating in each country contained different sets of high frequency mutations, many of which were known VOCs. Mutations within clusters increased in frequency simultaneously. Low frequency, but highly correlated mutations detected by the method could signal emerging VOCs, especially if they occur at higher frequency in other regions. An automated version of our method to find high frequency mutations in a set of SARS-COV-2 spike sequences is available online at http://curie.utmb.edu/SAR.html .

Introduction: A phase I, open-label clinical trial in healthy male subjects was conducted to assess the pharmacokinetic and safety profile of an oromucosal cannabinoid spray (AP701) containing a lipid-based nanoparticular drug formulation standardized to ∆-9-tetrahydrocannabinol (THC). Methods: Twelve healthy male subjects received a single dose of AP701 (12 sprays) containing 3.96 mg THC. Plasma samples were drawn 10 min–30 h post dose for analysis of THC and the active metabolite 11-hydroxy-∆-9-THC (11-OH-THC). Results: The single dose of the applied oromucosal cannabinoid spray AP701 (12 sprays, 3.96 mg THC) resulted in a mean maximum plasma concentration (Cmax) of 2.23 ng/mL (90% CI 1.22–3.24) and a mean overall exposure (area under the concentration-time curve from time 0 to last measurable concentration [AUC0–t]) of 7.74 h × ng/mL (90% CI 5.03–10.45) for THC. For the active metabolite 11-OH-THC, a Cmax of 2.09 mg/mL (90% CI 1.50–2.68) and AUC0–t of 10.4 h × ng/mL (90% CI 7.03–13.77) was found. The oromucosal cannabinoid spray AP701 caused only minor psychotropic effects despite the relatively high dosage applied by healthy subjects. No serious adverse effects occurred. Overall, the oromucosal cannabinoid spray AP701 was well tolerated. Conclusion: Compared to currently available drugs on the market, higher AUC values could be detected for the oromucosal cannabinoid spray AP701 despite administration of a lower dose. These comparatively higher blood levels caused only minor psychotropic adverse effects. The oromucosal cannabinoid spray AP701 was well tolerated at a single dose of 3.96 mg THC. The oromucosal administration may provide an easily applicable and titratable drug formulation with a high safety and tolerability profile.

In the present study on endocrine disrupting chemicals (EDCs) in treated wastewater, we used chemical and effect-based tools to analyse 56 wastewater treatment plant (WWTP) effluents from 15 European countries. The main objectives were (i) to compare three different receptor-based estrogenicity assays (ERα-GeneBLAzer, p-YES, ERα-CALUX®), and (ii) to investigate a combined approach of chemical target analysis and receptor-based testing for estrogenicity, glucocorticogenic activity, androgenicity and progestagenic activity (ERα-, GR-, AR- and PR-GeneBLAzer assays, respectively) in treated wastewater. A total of 56 steroids and phenols were detected at concentrations ranging from 25 pg/L (estriol, E3) up to 2.4 μg/L (cortisone). WWTP effluents, which passed an advanced treatment via ozonation or via activated carbon, were found to be less contaminated, in terms of lower or no detection of steroids and phenols, as well as hormone receptor-mediated effects. This result was confirmed by the effect screening, including the three ERα-bioassays. In the GeneBLAzer assays, ERα-activity was detected in 82 %, and GR-activity in 73 % of the samples, while AR- and PR-activity were only measured in 14 % and 21 % of the samples, respectively. 17β-estradiol was confirmed as the estrogen dominating the observed estrogenic mixture effect and triamcinolone acetonide was the dominant driver of glucocorticogenic activity. The comparison of bioanalytical equivalent concentrations (BEQ) predicted from the detected concentrations and the relative effect potency (BEQchem) with measured BEQ (BEQbio) demonstrated good correlations of chemical target analysis and receptor-based testing results with deviations mostly within a factor of 10. Bioassay-specific effect-based trigger values (EBTs) from the literature, but also newly calculated EBTs based on previously proposed derivation options, were applied and allowed a preliminary assessment of the water quality of the tested WWTP effluent samples. Overall, this study demonstrates the high potential of linking chemical with effect-based analysis in water quality assessment with regard to EDC contamination.

BackgroundA small group of people with epilepsy suffers from frequent seizures despite the available pharmacological and non-pharmacological interventions. The impact of epilepsy on these people extends beyond health-related quality of life (HRQoL), impacting a person's broader well-being and ability to participate in society. This study describes the burden of medically refractory epilepsy in people who suffer from daily to weekly seizures, in terms of HRQoL, well-being, and societal costs.MethodsData from the EPISODE study on (cost-) effectiveness of seizure dogs for adults with severe medically refractory epilepsy were used, collected in 25 patients during the first 12 months before they were partnered with a certified seizure dog. Data comprised seizure diaries covering 365 days and five three-monthly surveys, including the EQ-5D-5L, QOLIE-31-P, and ICECAP-A to measure HRQoL and well-being. A societal perspective was applied to estimate costs using the iMCQ and iPCQ questionnaires about healthcare use, informal care, and productivity losses.ResultsDaily seizure frequency and survey data were collected in 25 patients. A minimum of 114 observations was available for each instrument included in the survey. A total of 80% of participants experienced seizures on three or more days per week, with a median ranging from 1 to 17 seizures per seizure day. The mean EQ-5D-5L utility score was 0.682 (SD 0.235), which is considerably lower than the age-adjusted general population average. The mean QOLIE-31-P and ICECAP-A scores were 55.8 (SD 14.0) and 0.746 (SD 0.172), respectively. The average annual total cost amounted to €39,956 (range €3,804–€132,64). Informal care accounted for the largest share of costs (50%); those who received informal care reported, on average, 26 h per week (SD 30).ConclusionsSevere medically refractory epilepsy is associated with a considerable burden of illness at the patient and societal level. People with this condition have significantly reduced HRQoL and well-being and are limited in their ability to work while having substantial medical costs and a strong dependency on informal care.

Within the Human Biomonitoring for Europe initiative (HBM4EU), a study to determine new biomarkers of exposure to pesticides and to assess exposure patterns was conducted. Human urine samples (N = 2,088) were collected from five European regions in two different seasons. The objective of the study was to identify pesticides and their metabolites in collected urine samples with a harmonized suspect screening approach based on liquid chromatography coupled to high resolution mass spectrometry (LC-HRMS) applied in five laboratories. A combined data processing workflow included comprehensive data reduction, correction of mass error and retention time (RT) drifts, isotopic pattern analysis, adduct and elemental composition annotation, finalized by a mining of the elemental compositions for possible annotations of pesticide metabolites. The obtained tentative annotations (n = 498) were used for acquiring representative data-dependent tandem mass spectra (MS2) and verified by spectral comparison to reference spectra generated from commercially available reference standards or produced through human liver S9 in vitro incubation experiments. 14 parent pesticides and 71 metabolites (including 16 glucuronide and 11 sulfate conjugates) were detected. Collectively these related to 46 unique pesticides.For the remaining tentative annotations either (i) no data-dependent MS2 spectra could be acquired, (ii) the spectral purity was too low for sufficient matching, or (iii) RTs indicated a wrong annotation, leaving potential for more pesticides and/or their metabolites being confirmed in further studies. Thus, the reported results are reflecting only a part of the possible pesticide exposure.

Abstract Background Studies revealed the importance to assess dementia care dyads, composed of persons with dementia and their primary informal caregivers, in a differentiated way and to tailor support services to particular living and care circumstances. Therefore, this study aims first to identify classes of dementia care dyads that differ according to sociodemographic, care-related and dementia-specific characteristics and second, to compare these classes with regard to healthcare-related outcomes. Methods We used data from the cross-sectional German DemNet-D study (n = 551) and conducted a latent class analysis to investigate different classes of dementia care dyads. In addition, we compared these classes with regard to the use of health care services, caregiver burden (BIZA-D), general health of the informal caregiver (EQ-VAS) as well as quality of life (QoL-AD) and social participation (SACA) of the person with dementia. Furthermore, we compared the stability of the home-based care arrangements. Results Six different classes of dementia care dyads were identified, based on best Bayesian Information Criterion (BIC), significant likelihood ratio test (p

In this study, 56 effluent samples from 52 European wastewater treatment plants (WWTPs) were investigated for the occurrence of 499 emerging chemicals (ECs) and their associated potential risks to the environment. The two main objectives were (i) to extend our knowledge on chemicals occurring in treated wastewater, and (ii) to identify and prioritize compounds of concern based on three different risk assessment approaches for the identification of consensus mixture risk drivers of concern. Approaches include (i) PNEC and EQS-based regulatory risk quotients (RQs), (ii) species sensitivity distribution (SSD)-based hazard units (HUs) and (iii) toxic units (TUs) for three biological quality elements (BQEs) algae, crustacean, and fish.For this purpose, solid-phase extracts were analysed with wide-scope chemical target screening via liquid chromatography high-resolution mass spectrometry (LC-HRMS), resulting in 366 detected compounds, with concentrations ranging from 100 µg/L. The detected chemicals were categorized with respect to critical information relevant for risk assessment and management prioritization including: (1) frequency of occurrence, (2) measured concentrations, (3) use groups, (4) persistence & bioaccumulation, and (5) modes of action. A comprehensive assessment using RQ, HU and TU indicated exceedance of risk thresholds for the majority of effluents with RQ being the most sensitive metric. In total, 299 out of the 366 compounds were identified as mixture risk contributors in one of the approaches, while 32 chemicals were established as consensus mixture risk contributors of high concern, including a high percentage (66%) of pesticides and biocides. For samples which have passed an advanced treatment using ozonation or activated carbon (AC), consistently much lower risks were estimated.

The aquatic environment faces increasing threats from a variety of unregulated organic chemicals originating from human activities, collectively known as chemicals of emerging concern (CECs). These include pharmaceuticals, personal-care products, pesticides, surfactants, industrial chemicals, and their transformation products. CECs enter aquatic environments through various sources, including effluents from wastewater treatment plants, industrial facilities, runoff from agricultural and residential areas, as well as accidental spills. Data on the occurrence of CECs in the marine environment are scarce, and more information is needed to assess the chemical and ecological status of water bodies, and to prioritize toxic chemicals for further studies or risk assessment. In this study, we describe a monitoring campaign targeting CECs in surface waters at the Swedish west coast using, for the first time, an on-site large volume solid phase extraction (LVSPE) device. We detected up to 80 and 227 CECs in marine sites and the wastewater treatment plant (WWTP) effluent, respectively. The dataset will contribute to defining pollution fingerprints and assessing the chemical status of marine and freshwater systems affected by industrial hubs, agricultural areas, and the discharge of urban wastewater.

The introduction of plant extracts to mitigate the symptoms of “hay fever”, about a century ago, led to discoveries beginning sixty years ago on determining the sequences and eventually structures of allergenic proteins. As more proteins were cloned, there was a need to rapidly identify and categorize those with significant similarity to known allergens. The Structural Database of Allergenic Proteins (SDAP) was created at the beginning of the 21st century as the first cross-referenced website to allow rapid overview of the structures and sequences of allergenic proteins. SDAP provides a way to identify sequence and functional similarities between these proteins, despite the complex nomenclature system based on the Latin names of their different sources. A rapid FASTA search simplifies grouping allergens from the same structural or functional family. SDAP also provides an overview of the rapidly expanding literature on the sequence, structure and epitopes of allergenic proteins and a way to estimate the potential allergenicity of novel proteins based on rules provided by the IUIS. Twenty years and a pandemic later, the list of allergenic proteins and their attributes continues to grow. SDAP is expanding and improving to allow rapid access to all this information.

Abstract Background The 2014–2016 Ebola virus disease (EVD) outbreak in West Africa was the largest EVD outbreak recorded, which has triggered calls for investments that would facilitate an even earlier response. This study aims to estimate the costs and health effects of earlier interventions in Sierra Leone. Methods A deterministic and a stochastic compartment model describing the EVD outbreak was estimated using a variety of data sources. Costs and Disability-Adjusted Life Years were used to estimate and compare scenarios of earlier interventions. Results Four weeks earlier interventions would have averted 10,257 (IQR 4353–18,813) cases and 8835 (IQR 3766–16,316) deaths. This implies 456 (IQR 194–841) thousand DALYs and 203 (IQR 87–374) million $US saved. The greatest losses occurred outside the healthcare sector. Conclusions Earlier response in an Ebola outbreak saves lives and costs. Investments in healthcare system facilitating such responses are needed and can offer good value for money.

Ablative fractional laser treatment facilitates epidermal drug delivery, which might be an interesting option to increase the topical efficacy of biological drugs in a variety of dermatological diseases. This work aims at investigating safety and tolerability of this new treatment approach in patients with plaque-type psoriasis. Eight patients with plaque-type psoriasis were enrolled in this study. All patients received (i) ablative fractional laser microporation (AFL) of a psoriatic lesion with an Er:YAG laser + etanercept (ETA; Enbrel® solution for injection) (AFL-ETA), (ii) ETA alone on another lesion, and, if feasible, (iii) AFL alone on an additional lesion. Overall, all treatment arms showed a favorable safety profile. AFL-ETA improved the lesion-specific TPSS score by 1.75 vs. baseline, whereas ETA or AFL alone showed a TPSS score improvement of 0.75 points, a difference that was not statistically significant and might be attributable to differences in baseline scores. Topical administration of ETA to psoriatic plaques via AFL-generated micropores was generally well-tolerated. No special precautions seem necessary in future studies. Clinical benefit will need assessment in sufficiently powered follow-up studies.

Motivation: There is a need for rapid and easy-to-use, alignment-free methods to cluster large groups of protein sequence data. Commonly used phylogenetic trees based on alignments can be used to visualize only a limited number of protein sequences. DGraph, introduced here, is an application developed to generate 2-dimensional (2D) maps based on similarity scores for sequences. The program automatically calculates and graphically displays property distance (PD) scores based on physico-chemical property (PCP) similarities from an unaligned list of FASTA files. Such “PD-graphs” show the interrelatedness of the sequences, whereby clusters can reveal deeper connectivities. Results: Property distance graphs generated for flavivirus (FV), enterovirus (EV), and coronavirus (CoV) sequences from complete polyproteins or individual proteins are consistent with biological data on vector types, hosts, cellular receptors, and disease phenotypes. Property distance graphs separate the tick- from the mosquito-borne FV, cluster viruses that infect bats, camels, seabirds, and humans separately. The clusters correlate with disease phenotype. The PD method segregates the β-CoV spike proteins of severe acute respiratory syndrome (SARS), severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and Middle East respiratory syndrome (MERS) sequences from other human pathogenic CoV, with clustering consistent with cellular receptor usage. The graphs also suggest evolutionary relationships that may be difficult to determine with conventional bootstrapping methods that require postulating an ancestral sequence.

BackgroundRisk communication is a key component of public health interventions during an outbreak. As the coronavirus pandemic unfolded in late 2019, the World Health Organization (WHO) was at the forefront in the development of risk communication strategies. The WHO introduced a range of activities with the purpose of enabling the public to avail verified and timely information on COVID-19 prevention behaviors. Given the various WHO activities to protect the public health during COVID-19, it is important to investigate the extent of familiarity and uptake of the WHO recommendations among the public during the first wave of the pandemic.MethodsTo do this, we conducted a large-scale Pan-European survey covering around 7500 individuals that are representative of populations from seven European countries, collected online during April 2-April 15, 2020. We use descriptive statistics including proportions and correlations and graphical representations such as bar charts to analyze and display the data.ResultsOur findings suggest that information from the WHO in the context of COVID-19 is well trusted and acted upon by the public. Overall familiarity and adherence were quite high in most countries. Adherence was higher for social distancing recommendations compared to hygiene measures. Familiarity and adherence were higher among older, female, and highly educated respondents. However, country level heterogeneities were observed in the level of trust in information from the WHO, with countries severely affected by the pandemic reporting lower levels of trust.ConclusionOur findings call for efforts from health authorities to get regular feedback from the public on their familiarity and compliance with recommendations for preventive measures at all stages of the pandemic, to further develop and adapt risk communication as the pandemic evolves.

ABSTRACT Antibiotic resistance is an increasing threat to human health. In the case of Aspergillus fumigatus, which is both an environmental saprobe and an opportunistic human fungal pathogen, resistance is suggested to arise from fungicide use in agriculture, as the azoles used for plant protection share the same molecular target as the frontline antifungals used clinically. However, limiting azole fungicide use on crop fields to preserve their activity for clinical use could threaten the global food supply via a reduction in yield. In this study, we clarify the link between azole fungicide use on crop fields and resistance in a prototypical human pathogen through systematic soil sampling on farms in Germany and surveying fields before and after fungicide application. We observed a reduction in the abundance of A. fumigatus on fields following fungicide treatment in 2017, a finding that was not observed on an organic control field with only natural plant protection agents applied. However, this finding was less pronounced during our 2018 sampling, indicating that the impact of fungicides on A. fumigatus population size is variable and influenced by additional factors. The overall resistance frequency among agricultural isolates is low, with only 1 to 3% of isolates from 2016 to 2018 displaying resistance to medical azoles. Isolates collected after the growing season and azole exposure show a subtle but consistent decrease in susceptibility to medical and agricultural azoles. Whole-genome sequencing indicates that, despite the alterations in antifungal susceptibility, fungicide application does not significantly affect the population structure and genetic diversity of A. fumigatus in fields. Given the low observed resistance rate among agricultural isolates as well the lack of genomic impact following azole application, we do not find evidence that azole use on crops is significantly driving resistance in A. fumigatus in this context. IMPORTANCE Antibiotic resistance is an increasing threat to human health. In the case of Aspergillus fumigatus, which is an environmental fungus that also causes life-threatening infections in humans, antimicrobial resistance is suggested to arise from fungicide use in agriculture, as the chemicals used for plant protection are almost identical to the antifungals used clinically. However, removing azole fungicides from crop fields threatens the global food supply via a reduction in yield. In this study, we survey crop fields before and after fungicide application. We find a low overall azole resistance rate among agricultural isolates, as well as a lack of genomic and population impact following fungicide application, leading us to conclude azole use on crops does not significantly contribute to resistance in A. fumigatus.

Background: Treating migraine attacks early may improve outcome. The aim of this analysis was to investigate whether certain premonitory symptoms could be indicators for taking acute medication. Methods: We analyzed 3-month diary data recorded by 271 patients with episodic migraine and looked at all migraine-free intervals. For investigating the interaction between acute medication and neck discomfort associated with sensitivity to lights, noises, or odors, we used a marginal structural model and a Cox regression analysis adjusted for moderate or severe headache. Results: The patients (mean age 43 ± 15.4 years, 88% women) recorded a total of 20,219 diary days without migraine. In the marginal structural model analysis, the risk for occurrence of a migraine attack on the subsequent day was reduced when acute medication was used in the presence of neck discomfort associated with sensitivity to lights (hazard ratio 0.4; 95% confidence interval 0.2–0.7), noises (0.4; 0.3–0.7), or odors (0.2; 0.1–0.4). The marginal structural model showed lower risk of migraine attacks than the Cox regression analysis adjusted for moderate or severe headache in the majority of the cases. Conclusion: Migraine attacks may be prevented when acute medication is used in the presence of neck discomfort associated with sensitivity to lights, noises, or odors. The results of this study may stimulate further prospective trials.

Abstract Environmental water quality monitoring aims to provide the data required for safeguarding the environment against adverse biological effects from multiple chemical contamination arising from anthropogenic diffuse emissions and point sources. Here, we integrate the experience of the international EU-funded project SOLUTIONS to shift the focus of water monitoring from a few legacy chemicals to complex chemical mixtures, and to identify relevant drivers of toxic effects. Monitoring serves a range of purposes, from control of chemical and ecological status compliance to safeguarding specific water uses, such as drinking water abstraction. Various water sampling techniques, chemical target, suspect and non-target analyses as well as an array of in vitro, in vivo and in situ bioanalytical methods were advanced to improve monitoring of water contamination. Major improvements for broader applicability include tailored sampling techniques, screening and identification techniques for a broader and more diverse set of chemicals, higher detection sensitivity, standardized protocols for chemical, toxicological, and ecological assessments combined with systematic evidence evaluation techniques. No single method or combination of methods is able to meet all divergent monitoring purposes. Current monitoring approaches tend to emphasize either targeted exposure or effect detection. Here, we argue that, irrespective of the specific purpose, assessment of monitoring results would benefit substantially from obtaining and linking information on the occurrence of both chemicals and potentially adverse biological effects. In this paper, we specify the information required to: (1) identify relevant contaminants, (2) assess the impact of contamination in aquatic ecosystems, or (3) quantify cause–effect relationships between contaminants and adverse effects. Specific strategies to link chemical and bioanalytical information are outlined for each of these distinct goals. These strategies have been developed and explored using case studies in the Danube and Rhine river basins as well as for rivers of the Iberian Peninsula. Current water quality assessment suffers from biases resulting from differences in approaches and associated uncertainty analyses. While exposure approaches tend to ignore data gaps (i.e., missing contaminants), effect-based approaches penalize data gaps with increased uncertainty factors. This integrated work suggests systematic ways to deal with mixture exposures and combined effects in a more balanced way, and thus provides guidance for future tailored environmental monitoring.

Abstract Background The toxicological characterization of sediments is an essential task to monitor the quality of aquatic environments. Many hazardous pollutants may accumulate in sediments and pose a risk to the aquatic community. The present study provides an attempt to integrate a diagnostic whole mixture assessment workflow based on a slightly modified Danio rerio embryo acute toxicity test with chemical characterization. Danio rerio embryos were directly exposed to sieved sediment (≤ 63 μm) for 96 h. Sediment samples were collected from three polluted sites (Kramfors, Sundsvall and Örnsköldsvik) in the Gulf of Bothnia (Sweden) which are characterized by a long history of pulp and paper industry impact. Effect data were supported by chemical analyses of 237 organic pollutants and 30 trace elements. Results The results show that malformations and neurotoxic compounds are the main drivers of differentiation in chemical and effects analyses, respectively. Specific spinal cord malformations and delayed hatching were observed only in sediments from Kramfors while light hyperactivity was seen only after exposure to sediments from Sundsvall. Conclusions Our experiments demonstrate that specific chemical profiles lead to specific effect patterns in Danio rerio embryos. In fact, behavioral endpoints could help detect the exposure to neurotoxins, and the observation of body malformations seems to be a potential tool for the identification of site-specific pollutants as polychlorinated biphenyl (PCBs), brominated flame retardants (BFRs) and several pesticides. Overall, results show the suitability of Danio rerio embryos for the fast screening of sediment samples.

Abstract The present monitoring and assessment of the chemical status of water bodies fail to characterize the likelihood that complex mixtures of chemicals affect water quality. The European Collaborative Project SOLUTIONS suggests that this likelihood can be estimated with effect-based methods (EBMs) complemented by chemical screening and/or impact modeling. These methods should be used to identify the causes of impacted water quality and to develop programs of measures to improve water quality. Along this line of reasoning, effect-based methods are recommended for Water Framework Directive (WFD) monitoring to cover the major modes of action in the universe of environmentally relevant chemicals so as to evaluate improvements of water quality upon implementing the measures. To this end, a minimum battery of bioassays has been recommended including short-term toxicity to algae, Daphnia and fish embryos complemented with in vitro and short-term in vivo tests on mode-of-action specific effects as proxies for long-term toxicity. The likelihood of adverse impacts can be established with effect-based trigger values, which differentiate good from poor water quality in close alignment with Environmental Quality Standards for individual chemicals, while taking into account mixture toxicity. The use of EBMs is suggested in the WFD as one avenue to establish the likelihood of adverse effects due to chemical pollution in European water systems. The present paper has been written as one component of a series of policy briefs to support decisions on water quality monitoring and management under the WFD.

Silicon photomultipliers produced using standard complementary metal oxide semiconductor (CMOS) processes are at the basis of modern applications of sensors for weak photon fluxes. They allow in fact to integrate transistor-based electronic components within sensors and provide intelligent read-out strategies. In this paper, we investigate the scalability of a 0.35-μm CMOS process to large area devices. We report the design and characterization of SiPMs with a total area of 1, 4, and 9 mm2. Cross talk, photon detection efficiency at 420 nm, gain at 2.5 V overvoltage and breakdown voltage temperature coefficient do not depend on the total area of the sensor and are 10%, 35%, 2.5 x 106, and 35 mV/K, respectively. The dark count rate scales with the total area of the device as 180 kHz/mm2. The total output capacitance, the decay time of the single photon signal, and the single photon time resolution depend on the area of the device. We obtain a capacitance of 66.9, 270.2, and 554.0 pF, a decay time of (27.1±0.1) ns, (50.8±0.1) ns, and (78.2±0.1) ns and a single photon time resolution of (77.97±0.51) ps, (201.67 ± 0.98) ps, and (282.28 ± 0.86) ps for the 1, 4, and 9 mm2 SiPMs, respectively.

Humans and wildlife are exposed to an intractably large number of different combinations of chemicals via food, water, air, consumer products, and other media and sources. This raises concerns about their impact on public and environmental health. The risk assessment of chemicals for regulatory purposes mainly relies on the assessment of individual chemicals. If exposure to multiple chemicals is considered in a legislative framework, it is usually limited to chemicals falling within this framework and co-exposure to chemicals that are covered by a different regulatory framework is often neglected. Methodologies and guidance for assessing risks from combined exposure to multiple chemicals have been developed for different regulatory sectors, however, a harmonised, consistent approach for performing mixture risk assessments and management across different regulatory sectors is lacking. At the time of this publication, several EU research projects are running, funded by the current European Research and Innovation Programme Horizon 2020 or the Seventh Framework Programme. They aim at addressing knowledge gaps and developing methodologies to better assess chemical mixtures, by generating and making available internal and external exposure data, developing models for exposure assessment, developing tools for in silico and in vitro effect assessment to be applied in a tiered framework and for grouping of chemicals, as well as developing joint epidemiological-toxicological approaches for mixture risk assessment and for prioritising mixtures of concern. The projects EDC-MixRisk, EuroMix, EUToxRisk, HBM4EU and SOLUTIONS have started an exchange between the consortia, European Commission Services and EU Agencies, in order to identify where new methodologies have become available and where remaining gaps need to be further addressed. This paper maps how the different projects contribute to the data needs and assessment methodologies and identifies remaining challenges to be further addressed for the assessment of chemical mixtures.

Abstract The definition of priority substances (PS) according to the Water Framework Directive (WFD) helped to remove many of these chemicals from the market and to reduce their concentrations in the European water bodies. However, it could not prevent that many of these chemicals have been replaced by others with similar risks. Today, monitoring of the PS-based chemical status according to WFD covers only a tiny fraction of toxic risks, extensively ignores mixture effects and lacks incentives and guidance for abatement. Thus, we suggest complement this purely status-related approach with more holistic and solution-oriented monitoring, which at the same time helps to provide links to the ecological status. Major elements include (1) advanced chemical screening techniques supporting mixture risk assessment and unraveling of source-related patterns in complex mixtures, (2) effect-based monitoring for the detection of groups of chemicals with similar effects and the establishment of toxicity fingerprints, (3) effect-directed analysis of drivers of toxicity and (4) to translate chemical and toxicological fingerprints into chemical footprints for prioritization of management measures. The requirement of more holistic and solution-oriented monitoring of chemical contamination is supported by the significant advancement of appropriate monitoring tools within the last years. Non-target screening technology, effect-based monitoring and basic understanding of mixture assessment are available conceptually and in research but also increasingly find their way into practical monitoring. Substantial progress in the development, evaluation and demonstration of these tools, for example, in the SOLUTIONS project enhanced their acceptability. Further advancement, integration and demonstration, extensive data exchange and closure of remaining knowledge gaps are suggested as high priority research needs for the next future to bridge the gap between insufficient ecological status and cost-efficient abatement measures.

The possibility to design a silicon photomultiplier (SiPM) using standard CMOS processes represents the frontier of current low photon flux detectors. It allows an integrated development of both sensor and intelligent read-out electronics on the same technology line and enables to create intelligent devices with on-chip signal processing. We report the design and characterization of an SiPM composed of 20×20 microcells with size 50×50 μm2. The device exhibits 200-kHz/mm2 dark rate, 10% cross talk probability, 1.5% afterpulsing probability, and 5.35 × 106 intrinsic gain at 29-V operational voltage. It is obtained at a 0.35-μm CMOS technology node, which is compatible with the development of integrated electronics. In order to verify the potential application of the device to optical and radiation detection systems, we measure its photon detection efficiency and its response to LED light and scintillation light from an LySO crystal.

Abstract Protecting our water resources in terms of quality and quantity is considered one of the big challenges of the twenty-first century, which requires global and multidisciplinary solutions. A specific threat to water resources, in particular, is the increased occurrence and frequency of flood events due to climate change which has significant environmental and socioeconomic impacts. In addition to climate change, flooding (or subsequent erosion and run-off) may be exacerbated by, or result from, land use activities, obstruction of waterways, or urbanization of floodplains, as well as mining and other anthropogenic activities that alter natural flow regimes. Climate change and other anthropogenic induced flood events threaten the quantity of water as well as the quality of ecosystems and associated aquatic life. The quality of water can be significantly reduced through the unintentional distribution of pollutants, damage of infrastructure, and distribution of sediments and suspended materials during flood events. To understand and predict how flood events and associated distribution of pollutants may impact ecosystem and human health, as well as infrastructure, large-scale interdisciplinary collaborative efforts are required, which involve ecotoxicologists, hydrologists, chemists, geoscientists, water engineers, and socioeconomists. The research network “project house water” consists of a number of experts from a wide range of disciplines and was established to improve our current understanding of flood events and associated societal and environmental impacts. The concept of project house and similar seed fund and boost fund projects was established by the RWTH Aachen University within the framework of the German excellence initiative with support of the German research foundation (DFG) to promote and fund interdisciplinary research projects and provide a platform for scientists to collaborate on innovative, challenging research. Project house water consists of six proof-of-concept studies in very diverse and interdisciplinary areas of research (ecotoxicology, water, and chemical process engineering, geography, sociology, economy). The goal is to promote and foster high-quality research in the areas of water research and flood-risk assessments that combine and build off-laboratory experiments with modeling, monitoring, and surveys, as well as the use of applied methods and techniques across a variety of disciplines.

Economic evaluations of new youth mental health interventions require preference-based outcome measures that capture the broad benefits these interventions can have for adolescents. The Abbreviated Self Completion Teen-Addiction Severity Index (ASC T-ASI) was developed to meet the need for such a broader measure. It assesses self reported problems in seven important domains of adolescents' lives, including school performance and family relationships, and is intended for use in economic evaluations of relevant interventions. The aim of the current study was to present the ASC T-ASI and examine its validity as well as its ability to distinguish between adolescents with and without problems associated with substance use and delinquency. The validation study was conducted in a sample of adolescents (n = 167) aged 12-18 years, who received in- or outpatient care in a youth mental health and (enclosed) care facility in the Netherlands. To examine its feasibility, test-retest reliability, and convergent validity, respondents completed the ASC T-ASI, as well as the EQ-5D-3L and SDQ at baseline and after a two-week interval using a counterbalanced method. The ASC T-ASI descriptive system comprises seven domains: substance use, school, work, family, social relationships, justice, and mental health, each expressing self reported problems on a five-point Likert scale (ranging from having 'no problem' to having a 'very large problem'). The majority of respondents (>70%) completed the ASC T-ASI within 10 minutes and appraised the questions as (very) easy and (very) comprehensible. Test-retest reliability was adequate (Kw values 0.26-0.55). Correlations with the supplementary measures were moderate to high (rs 0.30-0.50), suggesting convergent validity. The ASC T-ASI is a promising and valid measure for assessing self reported problems in important domains in adolescents' lives, allowing benefits beyond health and health-related quality of life to be included in economic evaluations of youth mental health interventions. Future studies of the ASC T-ASI should consider the comprehensiveness of its domains and sensitivity to change.

The number of anthropogenic chemicals, manufactured, by-products, metabolites and abiotically formed transformation products, counts to hundreds of thousands, at present. Thus, humans and wildlife are exposed to complex mixtures, never one chemical at a time and rarely with only one dominating effect. Hence there is an urgent need to develop strategies on how exposure to multiple hazardous chemicals and the combination of their effects can be assessed. A workshop, “Advancing the Assessment of Chemical Mixtures and their Risks for Human Health and the Environment” was organized in May 2018 together with Joint Research Center in Ispra, EU-funded research projects and Commission Services and relevant EU agencies. This forum for researchers and policy-makers was created to discuss and identify gaps in risk assessment and governance of chemical mixtures as well as to discuss state of the art science and future research needs. Based on the presentations and discussions at this workshop we want to bring forward the following Key Messages: • We are at a turning point: multiple exposures and their combined effects require better management to protect public health and the environment from hazardous chemical mixtures. • Regulatory initiatives should be launched to investigate the opportunities for all relevant regulatory frameworks to include prospective mixture risk assessment and consider combined exposures to (real-life) chemical mixtures to humans and wildlife, across sectors. • Precautionary approaches and intermediate measures (e.g. Mixture Assessment Factor) can already be applied, although, definitive mixture risk assessments cannot be routinely conducted due to significant knowledge and data gaps. • A European strategy needs to be set, through stakeholder engagement, for the governance of combined exposure to multiple chemicals and mixtures. The strategy would include research aimed at scientific advancement in mechanistic understanding and modelling techniques, as well as research to address regulatory and policy needs. Without such a clear strategy, specific objectives and common priorities, research, and policies to address mixtures will likely remain scattered and insufficient. Keywords: Chemical mixtures, Environmental chemicals, Combined exposure, Mixture risk assessment, Risk management

The exposome encompasses an individual's exposure to exogenous chemicals, as well as endogenous chemicals that are produced or altered in response to external stressors. While the exposome concept has been established for human health, its principles can be extended to include broader ecological issues. The assessment of exposure is tightly interlinked with hazard assessment. Here, we explore if mechanistic understanding of the causal links between exposure and adverse effects on human health and the environment can be improved by integrating the exposome approach with the adverse outcome pathway (AOP) concept that structures and organizes the sequence of biological events from an initial molecular interaction of a chemical with a biological target to an adverse outcome. Complementing exposome research with the AOP concept may facilitate a mechanistic understanding of stress-induced adverse effects, examine the relative contributions from various components of the exposome, determine the primary risk drivers in complex mixtures, and promote an integrative assessment of chemical risks for both human and environmental health. Keywords: Exposome, AOP, Systems toxicology, Systems biology, Systems chemistry, Risk assessment

Non-targeted mass spectrometry (MS) has become an important method over recent years in the fields of metabolomics and environmental research. While more and more algorithms and workflows become available to process a large number of non-targeted data sets, there still exist few manually evaluated universal test data sets for refining and evaluating these methods. The first step of non-targeted screening, peak detection and refinement of it is arguably the most important step for non-targeted screening. However, the absence of a model data set makes it harder for researchers to evaluate peak detection methods. In this Data Descriptor, we provide a manually checked data set consisting of 255,000 EICs (5000 peaks randomly sampled from across 51 samples) for the evaluation on peak detection and gap-filling algorithms. The data set was created from a previous real-world study, of which a subset was used to extract and manually classify ion chromatograms by three mass spectrometry experts. The data set consists of the converted mass spectrometry files, intermediate processing files and the central file containing a table with all important information for the classified peaks.

In dit onderzoek bestuderen we de rol van participatief budgetteren in de relatie tussen rolambiguïteit en werk-gerelateerde stress. We analyseren de impact van het niveau van budgetparticipatie op de mate van werk-gerelateerde stress in situaties met hoge rolambiguïteit. De resultaten van de vragenlijst die we afnamen bij 218 managers wijst erop dat werk-gerelateerde stress lager is wanneer managers een hoog gepercipieerd niveau van budgetparticipatie ervaren dan wanneer deze perceptie laag is. Dit verschil is vooral belangrijk in situaties met een hoge rolambiguïteit, omdat participatief budgetteren daar kan dienen als louterend mechanisme.