| 1. |
- Klionsky, Daniel J., et al.
(författare)
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Guidelines for the use and interpretation of assays for monitoring autophagy
- 2012
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Ingår i: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
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Forskningsöversikt (refereegranskat)abstract
- In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
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| 2. |
- Stitziel, Nathan O., et al.
(författare)
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Coding Variation in ANGPTL4, LPL, and SVEP1 and the Risk of Coronary Disease
- 2016
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Ingår i: New England Journal of Medicine. - 0028-4793 .- 1533-4406. ; 374:12, s. 1134-1144
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND The discovery of low-frequency coding variants affecting the risk of coronary artery disease has facilitated the identification of therapeutic targets. METHODS Through DNA genotyping, we tested 54,003 coding-sequence variants covering 13,715 human genes in up to 72,868 patients with coronary artery disease and 120,770 controls who did not have coronary artery disease. Through DNA sequencing, we studied the effects of loss-of-function mutations in selected genes. RESULTS We confirmed previously observed significant associations between coronary artery disease and low-frequency missense variants in the genes LPA and PCSK9. We also found significant associations between coronary artery disease and low-frequency missense variants in the genes SVEP1 (p.D2702G; minor-allele frequency, 3.60%; odds ratio for disease, 1.14; P = 4.2x10(-10)) and ANGPTL4 (p.E40K; minor-allele frequency, 2.01%; odds ratio, 0.86; P = 4.0x10(-8)), which encodes angiopoietin-like 4. Through sequencing of ANGPTL4, we identified 9 carriers of loss-of-function mutations among 6924 patients with myocardial infarction, as compared with 19 carriers among 6834 controls (odds ratio, 0.47; P = 0.04); carriers of ANGPTL4 loss-of-function alleles had triglyceride levels that were 35% lower than the levels among persons who did not carry a loss-of-function allele (P = 0.003). ANGPTL4 inhibits lipoprotein lipase; we therefore searched for mutations in LPL and identified a loss-of-function variant that was associated with an increased risk of coronary artery disease (p.D36N; minor-allele frequency, 1.9%; odds ratio, 1.13; P = 2.0x10(-4)) and a gain-of-function variant that was associated with protection from coronary artery disease (p.S447*; minor-allele frequency, 9.9%; odds ratio, 0.94; P = 2.5x10(-7)). CONCLUSIONS We found that carriers of loss-of-function mutations in ANGPTL4 had triglyceride levels that were lower than those among noncarriers; these mutations were also associated with protection from coronary artery disease.
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| 3. |
- Webb, Thomas R., et al.
(författare)
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Systematic Evaluation of Pleiotropy Identifies 6 Further Loci Associated With Coronary Artery Disease
- 2017
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Ingår i: Journal of the American College of Cardiology. - : Elsevier BV. - 0735-1097 .- 1558-3597. ; 69:7, s. 823-836
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND Genome-wide association studies have so far identified 56 loci associated with risk of coronary artery disease (CAD). Many CAD loci show pleiotropy; that is, they are also associated with other diseases or traits.OBJECTIVES This study sought to systematically test if genetic variants identified for non-CAD diseases/traits also associate with CAD and to undertake a comprehensive analysis of the extent of pleiotropy of all CAD loci.METHODS In discovery analyses involving 42,335 CAD cases and 78,240 control subjects we tested the association of 29,383 common (minor allele frequency >5%) single nucleotide polymorphisms available on the exome array, which included a substantial proportion of known or suspected single nucleotide polymorphisms associated with common diseases or traits as of 2011. Suggestive association signals were replicated in an additional 30,533 cases and 42,530 control subjects. To evaluate pleiotropy, we tested CAD loci for association with cardiovascular risk factors (lipid traits, blood pressure phenotypes, body mass index, diabetes, and smoking behavior), as well as with other diseases/traits through interrogation of currently available genome-wide association study catalogs.RESULTS We identified 6 new loci associated with CAD at genome-wide significance: on 2q37 (KCNJ13-GIGYF2), 6p21 (C2), 11p15 (MRVI1-CTR9), 12q13 (LRP1), 12q24 (SCARB1), and 16q13 (CETP). Risk allele frequencies ranged from 0.15 to 0.86, and odds ratio per copy of the risk allele ranged from 1.04 to 1.09. Of 62 new and known CAD loci, 24 (38.7%) showed statistical association with a traditional cardiovascular risk factor, with some showing multiple associations, and 29 (47%) showed associations at p < 1 x 10(-4) with a range of other diseases/traits.CONCLUSIONS We identified 6 loci associated with CAD at genome-wide significance. Several CAD loci show substantial pleiotropy, which may help us understand the mechanisms by which these loci affect CAD risk.
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| 4. |
- Allan, Eric, et al.
(författare)
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Interannual variation in land-use intensity enhances grassland multidiversity
- 2014
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Ingår i: Proceedings of the National Academy of Sciences. - : Proceedings of the National Academy of Sciences. - 1091-6490 .- 0027-8424. ; 111:1, s. 308-313
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Tidskriftsartikel (refereegranskat)abstract
- Although temporal heterogeneity is a well-accepted driver of biodiversity, effects of interannual variation in land-use intensity (LUI) have not been addressed yet. Additionally, responses to land use can differ greatly among different organisms; therefore, overall effects of land-use on total local biodiversity are hardly known. To test for effects of LUI (quantified as the combined intensity of fertilization, grazing, and mowing) and interannual variation in LUI (SD in LUI across time), we introduce a unique measure of whole-ecosystem biodiversity, multidiversity. This synthesizes individual diversity measures across up to 49 taxonomic groups of plants, animals, fungi, and bacteria from 150 grasslands. Multidiversity declined with increasing LUI among grasslands, particularly for rarer species and aboveground organisms, whereas common species and belowground groups were less sensitive. However, a high level of interannual variation in LUI increased overall multidiversity at low LUI and was even more beneficial for rarer species because it slowed the rate at which the multidiversity of rare species declined with increasing LUI. In more intensively managed grasslands, the diversity of rarer species was, on average, 18% of the maximum diversity across all grasslands when LUI was static over time but increased to 31% of the maximum when LUI changed maximally over time. In addition to decreasing overall LUI, we suggest varying LUI across years as a complementary strategy to promote biodiversity conservation.
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| 5. |
- Álvarez-Ruiz, Rodrigo, et al.
(författare)
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Postflood Monitoring in a Subtropical Estuary and Benchmarking with PFASs Allows Measurement of Chemical Persistence on the Scale of Months
- 2021
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Ingår i: Environmental Science and Technology. - : American Chemical Society (ACS). - 0013-936X .- 1520-5851. ; 55:21, s. 14607-14616
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Tidskriftsartikel (refereegranskat)abstract
- Measurements of chemical persistence in natural environments can provide insight into behavior not easily replicated in laboratory studies. However, it is difficult to find environmental situations suitable for such measurements, particularly for substances with half-lives exceeding several weeks. The objective of this study was to demonstrate that a strategic postflood monitoring campaign can be used to quantify transformation half-lives on the scale of months in a real aquatic system. Water samples were collected in the upper Brisbane River estuary on 36 occasions over 37 weeks and analyzed for 127 pharmaceuticals and personal care products (PPCPs), pesticides, and perfluoroalkyl substances (PFASs). High quality time trend data were obtained for 41 substances. For many of these, data on the input of a wastewater treatment plant to the upper estuary were also obtained. A mass balance model of the estuary stretch was formulated and parametrized using PFASs as persistent benchmarking chemicals. Transformation half-life estimates were obtained for 10 PPCPs and 7 pesticides ranging from 18 to 260 days. Furthermore, insight was obtained into dominant transformation processes as well as the magnitude of chemical inputs to the estuary and their sources. The approach developed shows that under certain conditions, estuaries can be used to quantify the persistence of organic contaminants with half-lives of the order of several months.
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| 6. |
- Aquilante, Francesco, et al.
(författare)
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Molcas 8 : New capabilities for multiconfigurational quantum chemical calculations across the periodic table
- 2016
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Ingår i: Journal of Computational Chemistry. - : Wiley. - 0192-8651 .- 1096-987X. ; 37:5, s. 506-541
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Tidskriftsartikel (refereegranskat)abstract
- In this report, we summarize and describe the recent unique updates and additions to the Molcas quantum chemistry program suite as contained in release version 8. These updates include natural and spin orbitals for studies of magnetic properties, local and linear scaling methods for the Douglas-Kroll-Hess transformation, the generalized active space concept in MCSCF methods, a combination of multiconfigurational wave functions with density functional theory in the MC-PDFT method, additional methods for computation of magnetic properties, methods for diabatization, analytical gradients of state average complete active space SCF in association with density fitting, methods for constrained fragment optimization, large-scale parallel multireference configuration interaction including analytic gradients via the interface to the Columbus package, and approximations of the CASPT2 method to be used for computations of large systems. In addition, the report includes the description of a computational machinery for nonlinear optical spectroscopy through an interface to the QM/MM package Cobramm. Further, a module to run molecular dynamics simulations is added, two surface hopping algorithms are included to enable nonadiabatic calculations, and the DQ method for diabatization is added. Finally, we report on the subject of improvements with respects to alternative file options and parallelization.
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| 7. |
- Baduel, Christine, et al.
(författare)
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Discovery of novel per- and polyfluoroalkyl substances (PFASs) at a fire fighting training ground and preliminary investigation of their fate and mobility
- 2017
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Ingår i: Chemosphere. - Oxford, UK : Elsevier. - 0045-6535 .- 1879-1298. ; 185, s. 1030-1038
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Tidskriftsartikel (refereegranskat)abstract
- Aqueous film forming foams (AFFFs) have been released at fire training facilities for several decades resulting in the contamination of soil and groundwater by per- and polyfluoroalkyl substances (PFASs). AFFF compositions are proprietary and may contain a broad range of PFASs for which the chemical structures and degradation products are not known. In this study, high resolution quadrupole-time-of flight tandem mass spectrometry (LC-QTOF-MS/MS) in combination with data processing using filtering strategies was applied to characterize and elucidate the PFASs present in concrete extracts collected at a fire training ground after the historical use of various AFFF formulations. Twelve different fluorochemical classes, representing more than 60 chemicals, were detected and identified in the concrete extracts. Novel PFASs homologues, unmonitored before in environmental samples such as chlorinated PFSAs, ketone PFSAs, dichlorinated PFSAs and perfluoroalkane sulphonamides (FASAs) were detected in soil samples collected in the vicinity of the fire training ground. Their detection in the soil cores (from 0 to 2 m) give an insight on the potential mobility of these newly identified PFASs.
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| 8. |
- Bräunig, Jennifer, et al.
(författare)
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Fate and redistribution of perfluoroalkyl acids through AFFF-impacted groundwater
- 2017
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Ingår i: Science of the Total Environment. - : Elsevier. - 0048-9697 .- 1879-1026. ; 596, s. 360-368
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Tidskriftsartikel (refereegranskat)abstract
- Leaching of perfluoroalkyl acids (PFAAs) from a local point source, a fire-fighting training area, has led to extensive contamination of a groundwater aquifer which has spread underneath part of a nearby town, Oakey, situated in the State of Queensland, Australia. Groundwater is extracted by residents from privately owned wells for daily activities such as watering livestock and garden beds. The concentration of 10 PFAAs in environmental and biological samples (water, soil, grass, chicken egg yolk, serum of horses, cattle and sheep), as well as human serum was investigated to determine the extent of contamination in the town and discuss fate and redistribution of PFAAs. Perfluorooctane sulfonate (PFOS) was the dominant PFAA in all matrices investigated, followed by perfluorohexane sulfonate (PFHxS). PFOS concentrations measured in water ranged between <0.17-14 mu g/L, concentrations of PFHxS measured between <0.07-6 mu g/L. PFAAs were detected in backyards (soil, grass), livestock and chicken egg yolk. Significant differences (p < 0.01) in PFOS and PFHxS concentrations in two groups of cattle were found, one held within the contamination plume, the other in the vicinity but outside of the contamination plume. In human serum PFOS concentrations ranged from 38 to 381 mu g/L, while PFHxS ranged from 39 to 214 mu g/L. Highest PFOS concentrations measured in human serum were >30-fold higher compared to the general Australian population. Through use of contaminated groundwater secondary sources of PFAA contamination are created on private property, leading to further redistribution of contamination and creation of additional human exposure pathways.
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| 9. |
- Bu, Qingwei, et al.
(författare)
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Historical intake and elimination of polychlorinated biphenyls and organochlorine pesticides by the Australian population reconstructed from biomonitoring data
- 2015
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Ingår i: Environment International. - : Elsevier BV. - 0160-4120 .- 1873-6750. ; 74, s. 82-88
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Tidskriftsartikel (refereegranskat)abstract
- Quantifying the competing rates of intake and elimination of persistent organic pollutants (POPs) in the human body is necessary to understand the levels and trends of POPs at a population level. In this paper we reconstruct the historical intake and elimination of ten polychlorinated biphenyls (PCBs) and five organochlorine pesticides (OCPs) from Australian biomonitoring data by fitting a population-level pharmacokinetic (PK) model. Our analysis exploits two sets of cross-sectional biomonitoring data for PCBs and OCPs in pooled blood serum samples from the Australian population that were collected in 2003 and 2009. The modeled adult reference intakes in 1975 for PCB congeners ranged from 0.89 to 24.5 ng/kg bw/day, lower than the daily intakes of OCPs ranging from 73 to 970 ng/kg bw/day. Modeled intake rates are declining with half-times from 1.1 to 1.3 years for PCB congeners and 0.83 to 0.97 years for OCPs. The shortest modeled intrinsic human elimination half-life among the compounds studied here is 6.4 years for hexachlorobenzene, and the longest is 30 years for PCB-74. Our results indicate that it is feasible to reconstruct intakes and to estimate intrinsic human elimination half-lives using the population-level PK model and biomonitoring data only. Our modeled intrinsic human elimination half-lives are in good agreement with values from a similar study carried out for the population of the United Kingdom, and are generally longer than reported values from other industrialized countries in the Northern Hemisphere.
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| 10. |
- Callan, Anna, et al.
(författare)
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Maternal exposure to perfluoroalkyl acids measured in whole blood and birth outcomes in offspring
- 2016
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Ingår i: Science of the Total Environment. - Amsterdam, Netherlands : Elsevier. - 0048-9697 .- 1879-1026. ; 569-570, s. 1107-1113
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Tidskriftsartikel (refereegranskat)abstract
- Perfluoralkyl and polyfluoralkyl substances have been measured in plasma and serum of pregnant women as a measure of prenatal exposure. Increased concentrations of individual perfluoroalkyl acids (PFAAs), (typically perfluorooctanoic acid (PFOA) and perfluoroctane sulfonate (PFOS) have been reported to be associated with reductions in birth weight and other birth outcomes. We undertook a study of 14 PFAAs in whole blood (including PFOS, PFHxS, PFHpA, PFOA, PFNA, PFDA and PFUnDA) from 98 pregnant women in Western Australia from 2008 to 2011. Median concentrations (in μg/L) were: PFOS 1.99; PFHxS 0.33; PFOA 0.86; PFNA 0.30; PFDA 0.12 and PFUnDA 0.08. Infants born to women with the highest tertile of PFHxS exposure had an increased odds of being < 95% of their optimal birth weight (OR 3.5, 95% CI 1.1–11.5). Conversely, maternal blood concentrations of PFUnDA were associated with non-significant increases in average birth weight (+ 102 g, 95% CI − 41, 245) and significant increases in proportion of optimal birth weight (+ 4.7%, 95% CI 0.7, 8.8) per ln-unit change. This study has reported a range of PFAAs in the whole blood of pregnant women and suggests that PFHxS and PFUnDA may influence foetal growth and warrant further attention. Additional studies are required to identify the sources of PFAA exposure with a view to prevention, in addition to further studies investigating the long term health effects of these ubiquitous chemicals.
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| 11. |
- Chen, Yiqin, et al.
(författare)
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Persistent organic pollutants in infants and toddlers : Relationship between concentrations in matched plasma and faecal samples
- 2017
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Ingår i: Environment International. - : Elsevier BV. - 0160-4120 .- 1873-6750. ; 107, s. 82-88
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Tidskriftsartikel (refereegranskat)abstract
- Early-childhood biomonitoring of persistent organic pollutants (POPs) is challenging due to the logistic and ethical limitations associated with blood sampling. We investigated using faeces as a non-invasive matrix to estimate internal exposure to POPs. The concentrations of selected POPs were measured in matched plasma and faecal samples collected from 20 infants/toddlers (aged 13 +/- 4.8 months), including a repeat sample time point for 13 infants (similar to 5 months apart). We observed higher rates of POP quantification in faeces (2 g dry weight) than in plasma (0.5 mL). Among the five chemicals that had quantification frequencies over 50% in both matrices, except for HCB, log concentration in faeces (C-f) and blood (C-b) were correlated (r > 0.74, P < 0.05) for p.p'-dichlorodiphenyldichloroethylene (p,p'-DDE), 2,3', 4,4', 5-pentachlorobiphenyl (PCB118), 2,2', 3,4,4', 5'-pentachlorobiphenyl (PCB138) and 2,2', 4,4', 5,5'-pentachlorobiphenyl (PCB153). We determined faeces: plasma concentration ratios (K-fb), which can be used to estimate C-b from measurements of C-f for infants/toddlers. For a given chemical, the variation in K-fb across individuals was considerable (CV from 0.46 to 0.70). Between 5% and 50% of this variation was attributed to short-term intra-individual variability between successive faecal samples. This variability could be reduced by pooling faeces samples over several days. Some of the remaining variability was attributed to longer-term intra-individual variability, which was consistent with previously reported observations of a decrease in K-fb over the first year of life. The strong correlations between C-f and C-b demonstrate the promise of using faeces for biomonitoring of these compounds. Future research on the sources of variability in K-fb could improve the precision and utility of this technique.
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| 12. |
- Chen, Yiqin, et al.
(författare)
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Persistent organic pollutants in matched breast milk and infant faeces samples
- 2015
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Ingår i: Chemosphere. - : Elsevier BV. - 0045-6535 .- 1879-1298. ; 118, s. 309-314
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Tidskriftsartikel (refereegranskat)abstract
- Assessing blood concentration of persistent organic pollutants (POPs) in infants is difficult due to the ethical and practical difficulties in obtaining sufficient quantities of blood. To determine whether measuring POPs in faeces might reflect blood concentration during infancy, we measured the concentrations of a range of POPs (i.e. polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs) and organochlorine pesticides (OCPs)) in a pilot study using matched breast milk and infant faecal samples obtained from ten mother-child pairs. All infants were breast fed, with 8 of them also receiving solid food at the time of faecal sampling. In this small dataset faecal concentrations (range 0.01-41 ng g(-1) lipid) are strongly associated with milk concentrations (range 0.02-230 ng g(-1) lipid). Associations with other factors generally could not be detected in this dataset, with the exception of a small effect of age or growth. Different sources (external or internal) of exposure appeared to directly influence faecal concentrations of different chemicals based on different inter-individual variability in the faeces-to-milk concentration ratio R-fm. Overall, the matrix of faeces as an external measure of internal exposure in infants looks promising for some chemicals and is worth assessing further in larger datasets.
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| 13. |
- Dewapriya, Pradeep, et al.
(författare)
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Novel Per- and Polyfluoroalkyl Substances Discovered in Cattle Exposed to AFFF-Impacted Groundwater
- 2023
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Ingår i: Environmental Science and Technology. - 0013-936X .- 1520-5851. ; 57:36, s. 13635-13645
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Tidskriftsartikel (refereegranskat)abstract
- The leaching of per- and polyfluoroalkyl substances (PFASs) from Australian firefighting training grounds has resulted in extensive contamination of groundwater and nearby farmlands. Humans, farm animals, and wildlife in these areas may have been exposed to complex mixtures of PFASs from aqueous film-forming foams (AFFFs). This study aimed to identify PFAS classes in pooled whole blood (n = 4) and serum (n = 4) from cattle exposed to AFFF-impacted groundwater and potentially discover new PFASs in blood. Thirty PFASs were identified at various levels of confidence (levels 1a–5a), including three novel compounds: (i) perfluorohexanesulfonamido 2-hydroxypropanoic acid (FHxSA-HOPrA), (ii) methyl((perfluorohexyl)sulfonyl)sulfuramidous acid, and (iii) methyl((perfluorooctyl)sulfonyl)sulfuramidous acid, belonging to two different classes. Biotransformation intermediate, perfluorohexanesulfonamido propanoic acid (FHxSA-PrA), hitherto unreported in biological samples, was detected in both whole blood and serum. Furthermore, perfluoroalkyl sulfonamides, including perfluoropropane sulfonamide (FPrSA), perfluorobutane sulfonamide (FBSA), and perfluorohexane sulfonamide (FHxSA) were predominantly detected in whole blood, suggesting that these accumulate in the cell fraction of blood. The suspect screening revealed several fluoroalkyl chain-substituted PFAS. The results suggest that targeting only the major PFASs in the plasma or serum of AFFF-exposed mammals likely underestimates the toxicological risks associated with exposure. Future studies of AFFF-exposed populations should include whole-blood analysis with high-resolution mass spectrometry to understand the true extent of PFAS exposure.
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| 14. |
- Eriksson, Ulrika, 1972-, et al.
(författare)
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Temporal trends of PFSAs, PFCAs and selected precursors in Australian serum from 2002 to 2013
- 2017
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Ingår i: Environmental Pollution. - Oxford, United Kingdom : Elsevier. - 0269-7491 .- 1873-6424. ; 220:Pt A, s. 168-177
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Tidskriftsartikel (refereegranskat)abstract
- Per- and polyfluoroalkyl substances (PFASs) are a family of compounds that includes numerous compound classes. To date, only a subset of these PFASs have been studied thoroughly in the general population. In this study, pooled serum samples from Australia collected in 2002-2013 were analyzed for PFASs according to gender and age (age categories of 0-4 years, 5-15 years, 16-30 years, 31-45 years, 46-60 years, and >60 years), in total 54 pooled samples and 4920 individuals. Compound classes included were perfluorocarboxylic acids (PFCAs), perfluorosulfonic acids (PFSAs), and two groups of PFCA precursor compounds; polyfluoroalkyl phosphate diesters (diPAPs), and fluorotelomer sulfonic acids (FTSAs). Several PFASs that were not reported in previous studies of Australian serum samples were found in this sample set including; diPAPs, FTSAs, perfluoropentane sulfonic acid (PFPeS), perfluoroheptane sulfonic acid (PFHpS), perfluoroheptane carboxylic acid (PFHpA), perfluoroundecanoic acid (PFUnDA), perfluorododecanoic acid (PFDoDA), and perfluorotridecanoic acid (PFTrDA). Various temporal trends were observed with a significant reduction (p < 0.05) between 2002 and 2013 for 8:2 FTSA, perflurohexane sulfonic acid (PFHxS), PFHpS, PFOS, and perflurooctanoic acid (PFOA). Levels of longer-chained PFDA and PFUnDA started to decrease more recently, between 2006 and 2013, while PFDoDA increased during the same time period. Higher levels in younger age groups (0-4 and 5-15 years) compared to adults (>15 years) were found for 8:2 FTSA and PFHpA, while levels of PFHpS, PFOS, PFUnDA, PFDoDA and PFTrDA were higher in adult age groups compared to younger age groups. Gender-specific patterns were seen for PFOA, PFHxS, PFHpS and PFOS, where levels were lower in women. Changes in manufacturing processes were reflected in the temporal time trends, and differences in bioaccumulation potential between homologues could be associated with age trends. Our results emphasize the importance of including emerging classes of PFASs in biomonitoring studies.
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| 15. |
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| 16. |
- Freischmidt, Axel, et al.
(författare)
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Serum microRNAs in patients with genetic amyotrophic lateral sclerosis and pre-manifest mutation carriers
- 2014
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Ingår i: Brain. - : Oxford University Press (OUP). - 0006-8950 .- 1460-2156. ; 137:11, s. 2938-2950
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Tidskriftsartikel (refereegranskat)abstract
- Knowledge about the nature of pathomolecular alterations preceding onset of symptoms in amyotrophic lateral sclerosis is largely lacking. It could not only pave the way for the discovery of valuable therapeutic targets but might also govern future concepts of pre-manifest disease modifying treatments. MicroRNAs are central regulators of transcriptome plasticity and participate in pathogenic cascades and/or mirror cellular adaptation to insults. We obtained comprehensive expression profiles of microRNAs in the serum of patients with familial amyotrophic lateral sclerosis, asymptomatic mutation carriers and healthy control subjects. We observed a strikingly homogenous microRNA profile in patients with familial amyotrophic lateral sclerosis that was largely independent from the underlying disease gene. Moreover, we identified 24 significantly downregulated microRNAs in pre-manifest amyotrophic lateral sclerosis mutation carriers up to two decades or more before the estimated time window of disease onset; 91.7% of the downregulated microRNAs in mutation carriers overlapped with the patients with familial amyotrophic lateral sclerosis. Bioinformatic analysis revealed a consensus sequence motif present in the vast majority of downregulated microRNAs identified in this study. Our data thus suggest specific common denominators regarding molecular pathogenesis of different amyotrophic lateral sclerosis genes. We describe the earliest pathomolecular alterations in amyotrophic lateral sclerosis mutation carriers known to date, which provide a basis for the discovery of novel therapeutic targets and strongly argue for studies evaluating presymptomatic disease-modifying treatment in amyotrophic lateral sclerosis.
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| 17. |
- Gomis, Melissa I., et al.
(författare)
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Historical human exposure to perfluoroalkyl acids in the United States and Australia reconstructed from biomonitoring data using population-based pharmacokinetic modelling
- 2017
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Ingår i: Environment International. - : Elsevier BV. - 0160-4120 .- 1873-6750. ; 108, s. 92-102
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Tidskriftsartikel (refereegranskat)abstract
- Perfluorooctanoic acid (PFOA), perfluorooctanesulfonic acid (PFOS) and perfluorohexanesulfonic acid (PFHxS) are found in the blood of humans and wildlife worldwide. Since the beginning of the 21st century, a downward trend in the human body burden, especially for PFOS and PFOA, has been observed while there is no clear temporal trend in wildlife. The inconsistency between the concentration decline in human serum and in wildlife could be indicative of a historical exposure pathway for humans linked to consumer products that has been reduced or eliminated. In this study, we reconstruct the past human exposure trends in two different regions, USA and Australia, by inferring the historical intake from cross-sectional biomonitoring data of PFOS, PFOA and PFHxS using a population-based pharmacokinetic model. For PFOS in the USA, the reconstructed daily intake peaked at 4.5 ng/kg-bw/day between 1988 and 1999 while in Australia it peaked at 4.0 ng/kg-bw/day between 1984 and 1996. For PFOA in the USA and Australia, the peak reconstructed daily intake was 1.1 ng/kg-bw/day in 1995 and 3.6 ng/kg-bw/day in 1992, respectively, and started to decline in 2000 and 1995, respectively. The model could not be satisfactorily fitted to the biomonitoring data for PFHxS within reasonable boundaries for its intrinsic elimination half-life, and thus reconstructing intakes of PFHxS was not possible. Our results indicate that humans experienced similar exposure levels and trends to PFOS and PFOA in the USA and Australia. Our findings support the hypothesis that near-field consumer product exposure pathways were likely dominant prior to the phase-out in industrialized countries. The intrinsic elimination half-life, which represents elimination processes that are common for all humans, and elimination processes unique to women (i.e., menstruation, cord-blood transfer and breastfeeding) were also investigated. The intrinsic elimination half-lives for PFOS and PFOA derived from model fitting for men were 3.8 and 2.4 years, respectively, for the USA, and 4.9 and 2 years respectively for Australia. Our results show that menstruation is a depuration pathway for PFOA for women, similarly but to a lesser extent compared to previous reports for PFOS. However menstruation, cord-blood transfer and breastfeeding together do not fully explain the apparently more rapid elimination of PFOA and PFOS by women compared to men; the intrinsic elimination half-lives in women were up to 13% lower for PFOS and up to 12% lower for PFOA compared to the corresponding half-lives in men.
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| 18. |
- Heffernan, Amy L., et al.
(författare)
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Pooled biological specimens for human biomonitoring of environmental chemicals : Opportunities and limitations
- 2014
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Ingår i: Journal of Exposure Science and Environmental Epidemiology. - : Springer Science and Business Media LLC. - 1559-0631 .- 1559-064X. ; 24:3, s. 225-232
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Forskningsöversikt (refereegranskat)abstract
- Biomonitoring has become the “gold standard” in assessing chemical exposures, and has an important role in risk assessment. The pooling of biological specimens—combining multiple individual specimens into a single sample—can be used in biomonitoring studies to monitor levels of exposure and identify exposure trends or to identify susceptible populations in a cost-effective manner. Pooled samples provide an estimate of central tendency and may also reveal information about variation within the population. The development of a pooling strategy requires careful consideration of the type and number of samples collected, the number of pools required and the number of specimens to combine per pool in order to maximise the type and robustness of the data. Creative pooling strategies can be used to explore exposure–outcome associations, and extrapolation from other larger studies can be useful in identifying elevated exposures in specific individuals. The use of pooled specimens is advantageous as it saves significantly on analytical costs, may reduce the time and resources required for recruitment and, in certain circumstances, allows quantification of samples approaching the limit of detection. In addition, the use of pooled samples can provide population estimates while avoiding ethical difficulties that may be associated with reporting individual results.
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| 19. |
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| 20. |
- Kristan, Matej, et al.
(författare)
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The Visual Object Tracking VOT2016 Challenge Results
- 2016
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Ingår i: COMPUTER VISION - ECCV 2016 WORKSHOPS, PT II. - Cham : SPRINGER INT PUBLISHING AG. - 9783319488813 - 9783319488806 ; , s. 777-823
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Konferensbidrag (refereegranskat)abstract
- The Visual Object Tracking challenge VOT2016 aims at comparing short-term single-object visual trackers that do not apply pre-learned models of object appearance. Results of 70 trackers are presented, with a large number of trackers being published at major computer vision conferences and journals in the recent years. The number of tested state-of-the-art trackers makes the VOT 2016 the largest and most challenging benchmark on short-term tracking to date. For each participating tracker, a short description is provided in the Appendix. The VOT2016 goes beyond its predecessors by (i) introducing a new semi-automatic ground truth bounding box annotation methodology and (ii) extending the evaluation system with the no-reset experiment.
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| 21. |
- Kärrman, Anna, et al.
(författare)
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Levels of 12 perfluorinated chemicals in pooled Australian serum, collected 2002-2003, in relation to age, gender, and region
- 2006
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Ingår i: Environmental Science and Technology. - : American Chemical Society (ACS). - 0013-936X .- 1520-5851. ; 40:12, s. 3742-3748
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Tidskriftsartikel (refereegranskat)abstract
- Pooled serum samples from 3802 Australian residents were analyzed for four perfluoroalkylsulfonates, seven perfluoroalkylcarboxylates, and perfluorooctanesulfonamide (PFOSA). Serum was collected from men and women of five different age groups and from rural and urban regions in Australia. The highest mean concentration was obtained for perfluorooctane sulfonate (PFOS, 20.8 ng/mL) followed by perfluorooctanoic acid (PFOA, 7.6 ng/mL), perfluorohexane sulfonate (PFHxS, 6.2 ng/mL), perfluorononanoic acid (PFNA, 1.1 ng/mL), and PFOSA (0.71 ng/mL). Additional four PFCs were detected in 5-18% of the samples at concentrations near the detection limits (0.1-0.5 ng/mL). An increase in PFOS concentration with increasing age in both regions and genders was observed. The male pool levels of some of the age groups compared to females were higherfor PFOS, PFOA, and PFHxS. In contrast, PFNA concentrations were higher in the female pools. No substantial difference was found in levels of PFCs between the urban and rural regions. The levels are equal or higher than previously reported serum levels in Europe and Asia but lower compared to the U.S.A. These results suggest that emissions from production in the Northern Hemisphere are of less importance for human exposure.
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| 22. |
- McLachlan, Michael S., et al.
(författare)
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Removal of 293 organic compounds in 15 WWTPs studied with non-targeted suspect screening
- 2022
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Ingår i: Environmental Science. - : Royal Society of Chemistry (RSC). - 2053-1400 .- 2053-1419. ; 8:7, s. 1423-1433
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Tidskriftsartikel (refereegranskat)abstract
- Understanding how contaminant breakthrough in wastewater treatment plants is influenced by chemical structure and treatment technology is important for protecting the aquatic environment. In order to assess this question, consistent contaminant breakthrough measurements are required for a large number of chemicals. Using direct injection UHPLC-Orbitrap-MS/MS with data-dependent non-target data acquisition followed by suspect screening against a library of >7000 compounds with exact mass and MS2 spectra, we quantified the removal of 293 chemicals in 15 WWTPs with widely varying treatment technology. Principle component analysis showed a clear and consistent influence of treatment technology on contaminant breakthrough. Log breakthrough was significantly correlated with log TSS and log BOD in treated effluent for 71% and 68% of the chemicals, respectively. Chemicals were identified which could be used as indicators of the standard of wastewater treatment. Furthermore, chemicals were identified that could be used to predict the breakthrough of groups of other chemicals. A high degree of correlation was found for the breakthrough of different groups of chemicals, which suggests that the data could be used to develop models describing how chemical structure influences breakthrough or removal efficiency. Non-targeted suspect screening is a useful method for generating consistent WWTP breakthrough data for large numbers of chemicals.
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| 23. |
- Nguyen, Hue T., et al.
(författare)
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Background release and potential point sources of per- and polyfluoroalkyl substances to municipal wastewater treatment plants across Australia
- 2022
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Ingår i: Chemosphere. - : Elsevier BV. - 0045-6535 .- 1879-1298. ; 293
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Tidskriftsartikel (refereegranskat)abstract
- Wastewater treatment plants (WWTPs) are known to be significant sources of per- and polyfluoroalkyl substances (PFAS) to the environment. In this study, PFAS were measured in the influent of 76 municipal wastewater treatment plants (WWTPs) serving approximately 53% of the Australian population. Of fourteen target PFAS, twelve analytes including six C5–C10 perfluoroalkyl carboxylic acids (PFCAs), four C4-10 perfluoroalkyl sulfonic acids (PFSAs) and two fluorotelomer sulfonates (6:2 and 8:2 FTS) were detected. Of these, PFOS, PFHxS and PFHxA had the highest median concentrations. The per capita background release of Σ12 PFAS to WWTP influent in Australia was estimated to be 8.1–24 μg/d/per person. The background release was supplemented by contributions from catchment specific point sources (i.e., industry, airports, military bases, and landfills), whereby the number of industrial sites positively correlated with the per capita mass load of Σ12 PFAS (r = 0.5–0.63, p < 0.01). The per capita mass loads were extrapolated to the entire Australian population, with estimates suggesting that approximately 1 kg/d of Σ12 PFAS reach WWTPs in Australia (300–400 kg annually), with more than half of the PFAS (∼59%) attributed to background release and the remaining (∼41%) to catchment specific point sources. These data provide insight into the release of major PFAS to wastewater at a national scale in Australia.
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| 24. |
- Nilsson, Sandra, et al.
(författare)
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Analytical uncertainties in a longitudinal study : A case study assessing serum levels of per- and poly-fluoroalkyl substances (PFAS)
- 2021
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Ingår i: International journal of hygiene and environmental health. - : Urban & Fischer. - 1438-4639 .- 1618-131X. ; 238
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Tidskriftsartikel (refereegranskat)abstract
- Per- and poly-fluoroalkyl substances (PFAS) are a range of persistent organofluorine contaminants, some of which have been found to accumulate in humans and have long half-lives. In longitudinal studies, when relying on measurements obtained at different points in time, it is critical to understand the associated analytical uncertainties when interpreting the data. In this manuscript we assess precision measurements of serum PFAS analysis in a follow-up study undertaken approximately 5 years after the initial study. These measurements included intra-(n = 58) and inter-batch duplicates (n = 57), inter-batch replicates (n = 58), inter-laboratory replicates (n = 10) and a re-analysis of 120 archived serum samples from the initial study. Average coefficients of variation (CV) for perfluorooctanoic acid (PFOA), perfluorohexane sulfonate (PFHxS) and perfluorooctane sulfonate (PFOS) associated with the reanalysis of archived samples ranged from 4 to 8%, which was greater than the inter- and intra -batch duplicates (<3%), but lower than the inter-laboratory comparison (CV ≥ 10%). Multi-centre analytical capacity in studies increases the variance within the dataset and implementation of variability-measures are useful to refine and maintain comparability. Due to long PFAS half-lives, this variance is an important consideration when deciding appropriate time intervals for sample collections in longitudinal studies, to ensure the difference is greater than the analytical uncertainty.
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| 25. |
- Nilsson, Sandra, et al.
(författare)
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Biomonitoring of per- and polyfluoroalkyl substances (PFAS) exposure in firefighters : Study design and lessons learned from stakeholder and participant engagement
- 2022
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Ingår i: International journal of hygiene and environmental health. - : Elsevier. - 1438-4639 .- 1618-131X. ; 242
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Tidskriftsartikel (refereegranskat)abstract
- Firefighters may be occupationally exposed to per- and polyfluoroalkyl substances (PFASs) through Aqueous Film-Forming Foam (AFFF), smoke, dust and turnout gear, in addition to other background exposure sources. Epidemiological assessment of PFAS exposure in an occupational cohort of firefighting staff commenced in 2013-2014, following cessation of PFAS-based AFFF in Australian aviation. Here we present the study design and methodology of a follow-up study conducted in 2018-2019. We focus on our experiences engaging with stakeholders and participants with the establishment of an inclusive study group and highlight the key lessons learned from implementing a co-design process in the study. The study included a cross-sectional assessment of blood serum concentrations of 40 PFASs, including perfluorooctanoic acid (PFOA), perfluorooctane sulfonate (PFOS) and perfluorohexane sulfonate (PFHxS), and 14 health-related biomarkers in 799 current and former Aviation Rescue Firefighting Services employees. A large proportion (87%) of the participants from the preliminary exposure study in 2013-2014 were re-recruited in the follow-up study. This enabled further longitudinal analyses in this subset of 130 participants. Participants included employees from different work roles and timeframes, reflecting the periods when three different firefighting foams were utilised in Australia. Establishment of a collaborative and inclusive study group (including stakeholders and participants) contributed to several components of the study design, including the expansion of robust analytical quality assurance and control measurements, and tailoring of communication and dissemination strategies. These outcomes were key factors that improved transparency of the research design, methods and results. Additionally, implementing elements of co-design helped build trust between researchers and participants, which is an important consideration for studies funded by stakeholders related to the exposure source.
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| 26. |
- O'Malley, Elissa, et al.
(författare)
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The presence of selected UV filters in a freshwater recreational reservoir and fate in controlled experiments
- 2021
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Ingår i: Science of the Total Environment. - : Elsevier BV. - 0048-9697 .- 1879-1026. ; 754
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Tidskriftsartikel (refereegranskat)abstract
- UV filters present in sunscreen and other cosmetics are directly released into the environment during aquatic recreational activities. The extent to which the wide range of UV filters pose a risk to the environment remains unclear. This study investigated the occurrence and dissipation of selected organic UV filters at a recreational site (Enoggera Reservoir, Queensland, Australia) over 12 h. Furthermore, different possible degradation processes were investigated in a controlled off-site experiment with surface water exposed to natural light. Half-lives were estimated for ten UV filters. In Enoggera Reservoir, seven UV filters were detected, of which the most prevalent were octocrylene, avobenzone (BMDBM) and enzacamene (4-MBC). Summed concentrations of the seven UV filters ranged from 7330 ng L-1 at 13:00 h to 2550 ng L-1 at 21:00 h. In the degradation experiment, four UV filters showed no significant change over time. The fate of these compounds in the environment is likely to be mainly influenced by dispersion. Half-lives of the remaining UV filters were 6.6 h for amiloxate (IMC), 20 h for benzophenone 1, 23 h for octinoxate (EHMC), 30 h for 3-benzylidene camphor, 34 h for 4-MBC and 140 h for dioxybenzone (BP8). The degree of susceptibility to photodegradation and biodegradation was generally consistent within a structural class. The fate and half-lives of UV filters are variable and should be considered on a per site basis when assessing environmental risk.
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| 27. |
- Rotander, Anna, 1978-, et al.
(författare)
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Elevated levels of PFOS and PFHxS in firefighters exposed to aqueous film forming foam (AFFF)
- 2015
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Ingår i: Environment International. - Oxford, United Kingdom : Elsevier. - 0160-4120 .- 1873-6750. ; 82, s. 28-34
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Tidskriftsartikel (refereegranskat)abstract
- Exposure to aqueous film forming foam (AFFF) was evaluated in 149 firefighters working at AFFF training facilities in Australia by analysis of PFOS and related compounds in serum. A questionnaire was designed to capture information about basic demographic factors, lifestyle factors and potential occupational exposure (such as work history and self-reported skin contact with foam). The results showed that a number of factors were associated with PFAA serum concentrations. Blood donation was found to be linked to low PFAA levels, and the concentrations of PFOS and PFHxS were found to be positively associated with years of jobs with AFFF contact. The highest levels of PFOS and PFHxS were one order of magnitude higher compared to the general population in Australia and Canada. Study participants who had worked ten years or less had levels of PFOS that were similar to or only slightly above those of the general population. This coincides with the phase out of 3M AFFF from all training facilities in 2003, and suggests that the exposures to PFOS and PFHxS in AFFF have declined in recent years. Self-reporting of skin contact and frequency of contact were used as an index of exposure. Using this index, there was no relationship between PFOS levels and skin exposure. This index of exposure is limited as it relies on self-report and it only considers skin exposure to AFFF, and does not capture other routes of potential exposure. Possible associations between serum PFAA concentrations and five biochemical outcomes were assessed. The outcomes were serum cholesterol, triglycerides, high-density lipoproteins, low density lipoproteins, and uric acid. No statistical associations between any of these endpoints and serum PFAA concentrations were observed.
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| 28. |
- Rotander, Anna, et al.
(författare)
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Novel fluorinated surfactants tentatively identified in firefighters using liquid chromatography quadrupole time-of-flight tandem mass spectrometry and a case-control approach
- 2015
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Ingår i: Environmental Science and Technology. - : American Chemical Society (ACS). - 0013-936X .- 1520-5851. ; 49:4, s. 2434-2442
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Tidskriftsartikel (refereegranskat)abstract
- Fluorinated surfactant-based aqueous film-forming foams (AFFFs) are made up of per- and polyfluorinated alkyl substances (PFAS) and are used to extinguish fires involving highly flammable liquids. The use of perfluorooctanesulfonic acid (PFOS) and other perfluoroalkyl acids (PFAAs) in some AFFF formulations has been linked to substantial environmental contamination. Recent studies have identified a large number of novel and infrequently reported fluorinated surfactants in different AFFF formulations. In this study, a strategy based on a case-control approach using quadrupole time-of-flight tandem mass spectrometry (QTOF-MS/MS) and advanced statistical methods has been used to extract and identify known and unknown PFAS in human serum associated with AFFF-exposed firefighters. Two target sulfonic acids [PFOS and perfluorohexanesulfonic acid (PFHxS)], three non-target acids [perfluoropentanesulfonic acid (PFPeS), perfluoroheptanesulfonic acid (PFHpS), and perfluorononanesulfonic acid (PFNS)], and four unknown sulfonic acids (Cl-PFOS, ketone-PFOS, ether-PFHxS, and Cl-PFHxS) were exclusively or significantly more frequently detected at higher levels in firefighters compared to controls. The application of this strategy has allowed for identification of previously unreported fluorinated chemicals in a timely and cost-efficient way.
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| 29. |
- Rousis, Nikolaos I., et al.
(författare)
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Socioeconomic status and public health in Australia : A wastewater-based study
- 2022
-
Ingår i: Environment International. - : Elsevier BV. - 0160-4120 .- 1873-6750. ; 167
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Tidskriftsartikel (refereegranskat)abstract
- Analysis of untreated municipal wastewater is recognized as an innovative approach to assess population exposure to or consumption of various substances. Currently, there are no published wastewater-based studies investigating the relationships between catchment social, demographic, and economic characteristics with chemicals using advanced non-targeted techniques. In this study, fifteen wastewater samples covering 27% of the Australian population were collected during a population Census. The samples were analysed with a workflow employing liquid chromatography high-resolution mass spectrometry and chemometric tools for non-target analysis. Socioeconomic characteristics of catchment areas were generated using Geospatial Information Systems software. Potential correlations were explored between pseudo-mass loads of the identified compounds and socioeconomic and demographic descriptors of the wastewater catchments derived from Census data. Markers of public health (e.g., cardiac arrhythmia, cardiovascular disease, anxiety disorder and type 2 diabetes) were identified in the wastewater samples by the proposed workflow. They were positively correlated with descriptors of disadvantage in education, occupation, marital status and income, and negatively correlated with descriptors of advantage in education and occupation. In addition, markers of polypropylene glycol (PPG) and polyethylene glycol (PEG) related compounds were positively correlated with housing and occupation disadvantage. High positive correlations were found between separated and divorced people and specific drugs used to treat cardiac arrhythmia, cardiovascular disease, and depression. Our robust non-targeted methodology in combination with Census data can identify relationships between biomarkers of public health, human behaviour and lifestyle and socio-demographics of whole populations. Furthermore, it can identify specific areas and socioeconomic groups that may need more assistance than others for public health issues. This approach complements important public health information and enables large-scale national coverage with a relatively small number of samples.
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| 30. |
- Steinacker, Petra, et al.
(författare)
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Neurofilaments in the diagnosis of motoneuron diseases : a prospective study on 455 patients
- 2016
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Ingår i: Journal of Neurology, Neurosurgery and Psychiatry. - : BMJ. - 0022-3050 .- 1468-330X. ; 87:1, s. 12-20
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Tidskriftsartikel (refereegranskat)abstract
- Objectives Biomarkers for the diagnosis of motoneuron diseases (MND) are urgently needed to improve the diagnostic pathway, patient stratification and monitoring. The aim of this study was to validate candidate markers for MND in cerebrospinal fluid (CSF) and specify cut-offs based on large patient cohorts by especially considering patients who were seen under the initial differential diagnosis (MND mimics). Methods In a prospective study, we investigated CSF of 455 patients for neurofilament light chain (NfL), phosphorylated heavy chain (pNfH), tau protein (Tau) and phospho-tau protein (pTau). Analysed cohorts included patients with apparently sporadic and familial amyotrophic lateral sclerosis (ALS) and primary lateral sclerosis (PLS) (MND, n=253), MND mimics (n=85) and neurological control groups. Cut-off values were specified, and diagnostic performance and correlation with progression were analysed. Results Nfs were significantly higher in the MND group compared to the control groups, whereas Tau and pTau did not differ. At a cut-off level of 2200 pg/mL for NfL, a 77% diagnostic sensitivity (CI 71% to 82%), 85% specificity (CI 79% to 90%) and 87% positive predictive value (PPV) (CI 81% to 91%) were achieved. For pNfH, we calculated 83% sensitivity (CI 78% to 88%), 77% specificity (CI 71% to 83%) and 82% PPV (CI 77% to 86%) at 560 pg/mL. There were no significant differences between sporadic and genetic ALS or PLS. Nf levels were elevated at early disease stage, and correlated moderately with MND progression and duration. Conclusions Neurofilaments in CSF have a high relevance for the differential diagnosis of MNDs and should be included in the diagnostic work-up of patients. Their value as prognostic markers should be investigated further.
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| 31. |
- Toms, Leisa-Maree L., et al.
(författare)
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Triclosan in individual human milk samples from Australia
- 2011
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Ingår i: Chemosphere. - : Elsevier BV. - 0045-6535 .- 1879-1298. ; 85:11, s. 1682-1686
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Tidskriftsartikel (refereegranskat)abstract
- Triclosan is a chlorinated phenol ether that has been in widespread use as a broad-spectrum antibacterial agent for four decades. When compared to the limited international data available on human body burden of triclosan, results from a pooled blood study suggested that triclosan concentrations in Australia were a factor two higher than observed in Sweden. This study determined triclosan levels in individual human milk samples (n = 151) collected between 2002 and 2005 from primiparous Australian mothers. It provided the first report of population triclosan levels and individual variation in Australia and gave a measure of infant exposure via breast feeding. The distribution of triclosan concentration was positively skewed, with 7.2% of the samples below the LOQ 66% with a concentration of less than or equal to 1.0 ng g(-1) fresh weight and the remaining samples above 1 ng g(-1) reaching a maximum concentration of 19 ng g(-1) fresh weight. The mean and median triclosan concentrations were 1.3 +/- 2.7 ng g(-1) f.w. and 0.26 ng g(-1) f.w., respectively. The results of this study showed high variability in triclosan concentrations between individuals and no correlations with maternal age (p = 0.094), maternal weight (p = 0.971) or infant age at the time of sample collection (p = 0.621). A large number of samples contained low or non-quantifiable concentrations of triclosan and so, in Australia, ubiquitous background exposure due to environmental sources is low. This means that body burden can be influenced by an individual's use of triclosan containing product. Given that triclosan containing product use is continuing, it is important that monitoring in both humans and the environment is continued and that triclosan containing products are adequately labeled so that an individual can choose to avoid exposure.
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| 32. |
- Wong, Fiona, et al.
(författare)
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Enhanced Elimination of Perfluorooctane Sulfonic Acid by Menstruating Women : Evidence from Population-Based Pharmacokinetic Modeling
- 2014
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Ingår i: Environmental Science and Technology. - : American Chemical Society (ACS). - 0013-936X .- 1520-5851. ; 48:15, s. 8807-8814
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Tidskriftsartikel (refereegranskat)abstract
- Human biomonitoring studies have shown that concentrations of perfluorooctane sulfonic acid (PFOS) in men are higher than in women. We investigate sex differences in elimination of PFOS by fitting a population-based pharmacokinetic model to six cross-sectional data sets from 1999 to 2012 from the US National Health and Nutrition Examination Survey (NHANES) and derive human first-order elimination rate constants (k(E)) and corresponding elimination half-lives (t(1/2)) for PFOS, where t(1/2) = In 2/k(E). We use a modified version of the Ritter population-based pharmacokinetic model and derive elimination rate constants separately for men and women. The model accounts for population-average lifetime changes in PFOS intake, body weight, and menstruation rate. We compare the model-derived elimination rate constant for hypothetical nonmenstruating women to the elimination rate constant for men and women when menstruation is included as a loss process to evaluate the hypothesis that loss of PFOS by menstruation is an important process for women. The modeled elimination half-life for men is 4.7 years, and the modeled elimination half-life for women when excluding losses from menstruation is 3.7 years. The elimination half-life for women when menstruation is included in the model is 4.0 years. Thus, menstruation accounts for 3096 of the discrepancy in elimination of PFOS between men and women. The remaining discrepancy is likely due to other sex-specific elimination routes that are not considered in our modeling.
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| 33. |
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