| 1. |
- Hendriksen, Rene S., et al.
(författare)
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Global monitoring of antimicrobial resistance based on metagenomics analyses of urban sewage
- 2019
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- © 2019, The Author(s). Antimicrobial resistance (AMR) is a serious threat to global public health, but obtaining representative data on AMR for healthy human populations is difficult. Here, we use metagenomic analysis of untreated sewage to characterize the bacterial resistome from 79 sites in 60 countries. We find systematic differences in abundance and diversity of AMR genes between Europe/North-America/Oceania and Africa/Asia/South-America. Antimicrobial use data and bacterial taxonomy only explains a minor part of the AMR variation that we observe. We find no evidence for cross-selection between antimicrobial classes, or for effect of air travel between sites. However, AMR gene abundance strongly correlates with socio-economic, health and environmental factors, which we use to predict AMR gene abundances in all countries in the world. Our findings suggest that global AMR gene diversity and abundance vary by region, and that improving sanitation and health could potentially limit the global burden of AMR. We propose metagenomic analysis of sewage as an ethically acceptable and economically feasible approach for continuous global surveillance and prediction of AMR.
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| 2. |
- Nieuwenhuijse, David F., et al.
(författare)
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Setting a baseline for global urban virome surveillance in sewage
- 2020
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- © 2020, The Author(s). The rapid development of megacities, and their growing connectedness across the world is becoming a distinct driver for emerging disease outbreaks. Early detection of unusual disease emergence and spread should therefore include such cities as part of risk-based surveillance. A catch-all metagenomic sequencing approach of urban sewage could potentially provide an unbiased insight into the dynamics of viral pathogens circulating in a community irrespective of access to care, a potential which already has been proven for the surveillance of poliovirus. Here, we present a detailed characterization of sewage viromes from a snapshot of 81 high density urban areas across the globe, including in-depth assessment of potential biases, as a proof of concept for catch-all viral pathogen surveillance. We show the ability to detect a wide range of viruses and geographical and seasonal differences for specific viral groups. Our findings offer a cross-sectional baseline for further research in viral surveillance from urban sewage samples and place previous studies in a global perspective.
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| 3. |
- Adalbjörnsson, Stefan, et al.
(författare)
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Conjugate priors for Gaussian emission plsa recommender systems
- 2016
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Ingår i: 2016 24th European Signal Processing Conference, EUSIPCO 2016. - 9780992862657 ; 2016-November, s. 2096-2100
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Konferensbidrag (refereegranskat)abstract
- Collaborative filtering for recommender systems seeks to learn and predict user preferences for a collection of items by identifying similarities between users on the basis of their past interest or interaction with the items in question. In this work, we present a conjugate prior regularized extension of Hofmann's Gaussian emission probabilistic latent semantic analysis model, able to overcome the over-fitting problem restricting the performance of the earlier formulation. Furthermore, in experiments using the EachMovie and MovieLens data sets, it is shown that the proposed regularized model achieves significantly improved prediction accuracy of user preferences as compared to the latent semantic analysis model without priors.
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| 4. |
- Carlsson, Gunnar, et al.
(författare)
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Effluent from Bulk Drug Production is Toxic to Aquatic Vertebrates.
- 2009
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Ingår i: Environmental toxicology and chemistry. - : Wiley. - 0730-7268 .- 1552-8618. ; 28:12, s. 2656-2662
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Tidskriftsartikel (refereegranskat)abstract
- Very high levels of a range of pharmaceuticals have recently been reported in the effluent from a wastewater treatment plant near Hyderabad, India. The plant serves approximately 90 manufacturers of bulk drugs that primarily are exported to the world market. Fluoroquinolone antibiotics were found at levels that are highly toxic to various microorganisms. Despite that mg/L levels of drugs targeting human proteins have also been found, it is difficult to conclude whether these levels are sufficiently high to adversely affect fish or amphibians due to the lack of relevant chronic toxicity data for most human pharmaceuticals. To assess potential effects on aquatic vertebrates, tadpoles of Xenopus tropicalis were exposed to three dilutions of effluent (0.2, 0.6 and 2%) over 14 days, starting at developmental stage 51. Additionally, newly fertilized zebrafish (Danio rerio) were exposed to diluted effluent in 96-well plates for up to 144 hours post-fertilization (hpf). The tadpoles' body lengths, weights and developmental stages were recorded, whereas a larger number of sub-lethal and lethal endpoints were studied in the zebrafish. A 40% reduced growth of the exposed tadpoles was demonstrated at the lowest tested effluent concentration (0.2%), indicating that there are potent constituents in the effluent that can adversely affect aquatic vertebrates. The LC50 for zebrafish at 144 hpf was between 3.1 and 7.9% in different experiments. Reduced spontaneous movements, pigmentation and heart rate were recorded within 48 hpf at 8 and 16% effluent concentrations. Treated effluent from a plant, which serves as an important link in the global supply chain for bulk drugs, is thus shown to cause adverse effects to aquatic vertebrates even at very high dilutions.
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| 5. |
- Carlsson, Gunnar, et al.
(författare)
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Swimming activity in zebrafish larvae exposed to veterinary antiparasitic pharmaceuticals
- 2018
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Ingår i: Environmental toxicology and pharmacology. - : Elsevier BV. - 1382-6689 .- 1872-7077. ; 63, s. 74-77
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Tidskriftsartikel (refereegranskat)abstract
- Veterinary antiparasitic pharmaceuticals have been detected in surface waters and several of these pharmaceuticals act on the nervous system on the target organisms implying that neurological effects also might be of concern in non-target animals such as fish. We tested if exposure to antiparasitic pharmaceuticals affect swimming activity in 6 days old zebrafish larvae. The results revealed that most pharmaceuticals did not cause any effects in swimming activity. However, larvae exposed to 0.58 mg/L doramectin displayed reduced swimming activity even though they were classified as normal, having no morphological abnormalities.
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| 6. |
- Chelcea, Ioana C., 1994-
(författare)
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Computational methods for assessing chemical risk : focusing on toxicokinetic modelling in zebrafish (danio rerio)
- 2023
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- New chemicals are constantly produced and large data gaps exist on hazards of currently used industrial chemicals, stressing the need for rapid, ethically sound and cost-efficient hazard assessment methods. Traditional methods for effect assessment based on animal testing, do not meet these requirements and thus the toxicology field has been moving towards the development of new approach methodologies which include in vitro approaches but also computational methods. The current work has mainly focused on computational tools but also employed in vitro and in vivo methodologies for the development and validation of the in silico approaches.We firstly explored chemical variation of emerging chemicals as a basis for selecting sub-groups of per- and polyfluoroalkyl substances (PFASs) and bisphenols for Papers I and II. These compounds can be used for future testing and as case study compounds for in silico tools development. The PFASs selection showed compounds with large differences in structure and highlighted the lack of knowledge for large parts of the PFASs chemical domain. This likely is the main driver of the low predictive accuracy of some current fate models and the need for expanding their applicability domains. In Paper II we investigated the toxicokinetics of selected bisphenols in a commonly studied model organism, the zebrafish (Danio rerio), and developed a physiologically-based toxicokinetic model. Novel data for fish biotransformation was derived and showed lower rates than those measured in humans, providing valuable insight for both model parameterization and for chemical safety assessment using fish. The model also demonstrated the ability to predict and rank hazard of these bisphenols in terms of organ-specific bioaccumulation making it a useful tool for chemical screening and prioritization efforts. The results indicate that bisphenols AP, C and Z as well as tetrabromo bisphenol A may have larger potential for bioaccumulation than the widely used bisphenol A (BPA), indicating that these compounds do not constitute safer industrial substitutions. Lastly, we present in Paper III the development of a toxicokinetic model for the zebrafish embryo life-stage. Since the zebrafish embryo test is widely applied in toxicology research, the developed model provides a tool to better understand how varying testing conditions may affect dose at target thus providing a means to compare internal effect concentrations. Additionally, we applied the model in combination with data on estrogenic activity in order to rank the relative hazard of investigated bisphenols, which showed that bisphenols AF, C, B and Z may be more hazardous than BPA.Overall the developed computational tools showed good predictive performance and improvements in parameterization, thus providing tools for understanding dose at target and toxicokinetic variation of emerging substances. Furthermore, the thesis presents novel data and findings for per- and polyfluoroalkyl substances and bisphenols, which are environmental pollutants of emerging concern of relevance for future hazard assessments and substitution processes.
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| 7. |
- Chelcea, Ioana C., et al.
(författare)
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Investigating the OECD database of per- And polyfluoroalkyl substances-chemical variation and applicability of current fate models
- 2020
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Ingår i: Environmental Chemistry. - : CSIRO. - 1448-2517 .- 1449-8979. ; 17:7, s. 498-508
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Tidskriftsartikel (refereegranskat)abstract
- Many per- and polyfluoroalkyl substances (PFASs) have been identified in the environment, and some have been shown to be extremely persistent and even toxic, thus raising concerns about their effects on human health and the environment. Despite this, little is known about most PFASs. In this study, the comprehensive database of over 4700 PFAS entries recently compiled by the OECD was curated and the chemical variation was analysed in detail. The analysis revealed 3363 individual PFASs with a huge variation in chemical functionalities and a wide range of mixtures and polymers. A hierarchical clustering methodology was employed on the curated database, which resulted in 12 groups, where only half were populated by well-studied compounds thus indicating the large knowledge gaps. We selected both a theoretical and a procurable training set that covered a substantial part of the chemical domain based on these clusters. Several computational models to predict physicochemical and environmental fate related properties were assessed, which indicated their lack of applicability for PFASs and the urgent need for experimental data for training and validating these models. Our findings indicate reasonable predictions of the octanol-water partition coefficient for a small chemical domain of PFASs but large data gaps and uncertainties for water solubility, bioconcentration factor, and acid dissociation factor predictions. Improved computational tools are necessary for assessing risks of PFASs and for including suggested training set compounds in future testing of both physicochemical and effect-related data. This should provide a solid basis for better chemical understanding and future model development purposes.
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| 8. |
- Chelcea, Ioana C., et al.
(författare)
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Physiologically Based Toxicokinetic Modeling of Bisphenols in Zebrafish (Danio rerio) Accounting for Variations in Metabolic Rates, Brain Distribution, and Liver Accumulation
- 2022
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Ingår i: Environmental Science and Technology. - : American Chemical Society (ACS). - 0013-936X .- 1520-5851. ; 56:14, s. 10216-10228
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Tidskriftsartikel (refereegranskat)abstract
- Bisphenol A (BPA) is an industrial chemical, which has raised human health and environmental concerns due to its endocrine-disrupting properties. BPA analogues are less well-studied despite their wide use in consumer products. These analogues have been detected in water and aquatic organisms around the world, with some analogues showing toxic effects in various species including fish. Here, we present novel organ-specific time-course distribution data of bisphenol Z (BPZ) in female zebrafish (Danio rerio), including concentrations in the ovaries, liver, and brain, a rarely sampled organ with high toxicological relevance. Furthermore, fish-specific in vitro biotransformation rates were determined for 11 selected bisphenols. A physiologically based toxicokinetic (PBTK) model was adapted for four of these bisphenols, which was able to predict levels in the gonads, liver, and brain as well as the whole body within a 2-5-fold error with respect to experimental data, covering several important target organs of toxicity. In particular, predicted liver concentrations improved compared to currently available PBTK models. Predicted data indicate that studied bisphenols mainly distribute to the carcass and gonads and less to the brain. Our model provides a tool to increase our understanding on the distribution and kinetics of a group of emerging pollutants.
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| 9. |
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| 10. |
- Chelcea, Ioana C., 1994-, et al.
(författare)
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Physiology-informed toxicokinetic model for the zebrafish embryo test developed for bisphenols
- 2023
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Ingår i: Chemosphere. - : Elsevier. - 0045-6535 .- 1879-1298. ; 345
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Tidskriftsartikel (refereegranskat)abstract
- Zebrafish embryos (ZFE) is a widely used model organism, employed in various research fields including toxicology to assess e.g., developmental toxicity and endocrine disruption. Variation in effects between chemicals are difficult to compare using nominal dose as toxicokinetic properties may vary. Toxicokinetic (TK) modeling is a means to estimate internal exposure concentration or dose at target and to enable extrapolation between experimental conditions and species, thereby improving hazard assessment of potential pollutants. In this study we advance currently existing TK models for ZFE with physiological ZFE parameters and novel experimental bisphenol data, a class of chemicals with suspected endocrine activity. We developed a five-compartment model consisting of water, plastic, chorion, yolk sack and embryo in which surface area and volume changes as well as the processes of biotransformation and blood circulation influence mass fluxes. For model training and validation, we measured internal concentrations in ZFE exposed individually to BPA, bisphenol AF (BPAF) and Z (BPZ). Bayesian inference was applied for parameter calibration based on the training data set of BPZ. The calibrated TK model predicted internal ZFE concentrations of the majority of external test data within a 5-fold error and half of the data within a 2-fold error for bisphenols A, AF, F, and tetrabromo bisphenol A (TBBPA). We used the developed model to rank the hazard of seven bisphenols based on predicted internal concentrations and measured in vitro estrogenicity. This ranking indicated a higher hazard for BPAF, BPZ, bisphenol B and C (BPB, BPC) than for BPA.
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