| 51. |
- Schmidt, Amand F., et al.
(författare)
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Phenome-wide association analysis of LDL-cholesterol lowering genetic variants in PCSK9
- 2019
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Ingår i: BMC Cardiovascular Disorders. - : BMC. - 1471-2261 .- 1471-2261. ; 19:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: We characterised the phenotypic consequence of genetic variation at the PCSK9 locus and compared findings with recent trials of pharmacological inhibitors of PCSK9. Methods: Published and individual participant level data (300,000+ participants) were combined to construct a weighted PCSK9 gene-centric score (GS). Seventeen randomized placebo controlled PCSK9 inhibitor trials were included, providing data on 79,578 participants. Results were scaled to a one mmol/L lower LDL-C concentration. Results: The PCSK9 GS (comprising 4 SNPs) associations with plasma lipid and apolipoprotein levels were consistent in direction with treatment effects. The GS odds ratio (OR) for myocardial infarction (MI) was 0.53 (95% CI 0.42; 0.68), compared to a PCSK9 inhibitor effect of 0.90 (95% CI 0.86; 0.93). For ischemic stroke ORs were 0.84 (95% CI 0.57; 1.22) for the GS, compared to 0.85 (95% CI 0.78; 0.93) in the drug trials. ORs with type 2 diabetes mellitus (T2DM) were 1.29 (95% CI 1.11; 1.50) for the GS, as compared to 1.00 (95% CI 0.96; 1.04) for incident T2DM in PCSK9 inhibitor trials. No genetic associations were observed for cancer, heart failure, atrial fibrillation, chronic obstructive pulmonary disease, or Alzheimer's disease - outcomes for which large-scale trial data were unavailable. Conclusions: Genetic variation at the PCSK9 locus recapitulates the effects of therapeutic inhibition of PCSK9 on major blood lipid fractions and MI. While indicating an increased risk of T2DM, no other possible safety concerns were shown; although precision was moderate.
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| 52. |
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| 53. |
- Waldenstrom, U, et al.
(författare)
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Team midwife care: maternal and infant outcomes
- 2001
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Ingår i: The Australian & New Zealand journal of obstetrics & gynaecology. - : Wiley. - 0004-8666 .- 1479-828X. ; 41:3, s. 257-264
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Tidskriftsartikel (refereegranskat)
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| 54. |
- Adolfsson-Erici, Margaretha, et al.
(författare)
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A flow-through passive dosing system for continuously supplying aqueous solutions of hydrophobic chemicals to bioconcentration and aquatic toxicity tests
- 2012
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Ingår i: Chemosphere. - : Elsevier BV. - 0045-6535 .- 1879-1298. ; 86:6, s. 593-599
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Tidskriftsartikel (refereegranskat)abstract
- A continuous supply of water with defined stable concentrations of hydrophobic chemicals is a requirement in a range of laboratory tests such as the OECD 305 protocol for determining the bioconcentration factor in fish. Satisfying this requirement continues to be a challenge, particularly for hydrophobic chemicals. Here we present a novel solution based on equilibrium passive dosing. It employs a commercially available unit consisting of similar to 16000 polydimethylsiloxane (PDMS) tubes connected to two manifolds. The chemicals are loaded into the unit by repeatedly perfusing it with a methanol solution of the substances that is progressively diluted with water. Thereafter the unit is perfused with water and the chemicals partition from the unit into the water. The system was tested with nine chemicals with logK(ow) ranging from 4.1 to 6.3. The aqueous concentrations generated were shown to be largely independent of the water flow rate, and the unit to unit reproducibility was within a factor of similar to 2. In continuous flow experiments the aqueous concentrations of most of the study chemicals remained constant over 8 d. A model was assembled that allows prediction of the operating characteristics of the system from the logKow or PDMS/water partition coefficient of the chemical. The system is a simple, safe, predictable and flexible tool that generates stable aqueous concentrations of hydrophobic chemicals.
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| 55. |
- Adolfsson-Erici, Margaretha, et al.
(författare)
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In-vivo passive sampling to measure elimination kinetics in bioaccumulation tests
- 2012
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Ingår i: Chemosphere. - : Elsevier BV. - 0045-6535 .- 1879-1298. ; 88:1, s. 62-68
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Tidskriftsartikel (refereegranskat)abstract
- The application of in-tissue passive sampling to quantify chemical kinetics in fish bioconcentration experiments was investigated. A passive sampler consisting of an acupuncture needle covered with a PDMS tube was developed together with a method for its deployment in rainbow trout. The time to steady state for chemical uptake into the passive sampler was >1 d, so it was employed as a kinetically limited sampler with a deployment time of 2 h. The passive sampler was employed in parallel with the established whole tissue extraction method to study the elimination kinetics of 10 diverse chemicals in rainbow trout. 4-n-nonylphenol and 2,4,6-tri-tert-butylphenol were close to or below the limit of quantification in the sampler. For chlorpyrifos, musk xylene, hexachlorobenzene, 2,5-dichlorobiphenyl and p,p'-DDT. the elimination rate constants determined with the passive sampler method and the established method agreed within 18%. Poorer agreement (35%) was observed for 2,3,4-trichloroanisole and p-diisopropylbenzene because fewer data were obtained with the passive sampling method due to its lower sensitivity. The work shows that in-tissue passive sampling can be employed to measure contaminant elimination kinetics in fish. This opens up the possibility of studying contaminant kinetics in individual fish, thereby reducing the fish requirements and analytical costs for the determination of bioconcentration factors.
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| 56. |
- Adolfsson-Erici, Margaretha, et al.
(författare)
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Internal Benchmarking Improves Precision and Reduces Animal Requirements for Determination of Fish Bioconcentration Factors
- 2012
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Ingår i: Environmental Science and Technology. - : American Chemical Society (ACS). - 0013-936X .- 1520-5851. ; 46:15, s. 8205-8211
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Tidskriftsartikel (refereegranskat)abstract
- The enactment of new chemical regulations has generated a large need for the measurement of the fish bioconcentration factor (BCF). Past experience shows that the BCF determination lacks precision, requires large numbers of fish, and is costly. A new protocol was tested that shortens the experiment from up to 12 weeks for existing protocols to 2 weeks and reduces the number of fish by a factor of 5, while introducing internal benchmarking for the BCF determination. Rainbow trout were simultaneously exposed to 11 chemicals. The BCFs were quantified using one of the test chemicals, musk xylene, as a benchmark. These were compared with BCFs measured in a parallel experiment based on the OECD 305 guideline. The agreement was <20% for five chemicals and between 20%-25% for two further, while two chemicals lay outside the BCF operating window of the experiment and one was lost due to analytical difficulties. This agreement is better than that observed in a BCF Gold Standard Database. Internal benchmarking allows the improvement of the precision of BCF determination in parallel to large reduction in costs and fish requirements.
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| 57. |
- Adolfsson-Erici, Margaretha, et al.
(författare)
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Measuring bioconcentration factors in fish using exposure to multiple chemicals and internal benchmarking to correct for growth dilution
- 2012
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Ingår i: Environmental Toxicology and Chemistry. - : Wiley. - 0730-7268 .- 1552-8618. ; 31:8, s. 1853-1860
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Tidskriftsartikel (refereegranskat)abstract
- Modern chemical legislation requires measuring the bioconcentration factor (BCF) of large numbers of chemicals in fish. The BCF must be corrected for growth dilution, because fish growth rates vary between laboratories. Two hypotheses were tested: (1) that BCFs of multiple chemicals can be measured simultaneously in one experiment, and (2) that internal benchmarking using a conservative test substance in the chemical mixture can be used to correct for growth dilution. Bioconcentration experiments were conducted following major elements of the OECD 305 guideline. Fish were simultaneously exposed to 11 chemicals selected to cover a range of BCFs and susceptibility to biotransformation. A method was developed to calculate the growth-corrected elimination rate constant from the concentration ratio of the analyte and a benchmarking chemical for which growth dilution dominated other elimination mechanisms. This method was applied to the experimental data using hexachlorobenzene as the benchmarking chemical. The growth dilution correction lowered the apparent elimination rate constants by between 5% and a factor of four for eight chemicals, while for two chemicals the growth-corrected elimination rate constant was not significantly different from zero. The benchmarking method reduced the uncertainty in the elimination rate constant compared to the existing method for growth dilution correction. The BCFs from exposing fish to 10 chemicals at once were consistent with BCF values from single-chemical exposures from the literature, supporting hypothesis 1. Environ. Toxicol. Chem. 2012; 31: 18531860. (c) 2012 SETAC
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| 58. |
- 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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| 59. |
- Armitage, James M, et al.
(författare)
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A model assessment of polychlorinated dibenzo-p-dioxin and dibenzofuran sources and fate in the Baltic Sea.
- 2009
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Ingår i: Science of the Total Environment. - : Elsevier BV. - 0048-9697 .- 1879-1026. ; 407:12, s. 3784-3792
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Tidskriftsartikel (refereegranskat)abstract
- The contamination of the Baltic Sea with polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) has resulted in restrictions on the marketing and consumption of Baltic Sea fish, making this a priority environmental issue in the European Union. To date there is no consensus on the relative importance of different sources of PCDD/Fs to the Baltic Sea, and hence no consensus on how to address this issue. In this work we synthesized the available information to create a PCDD/F budget for the Baltic Sea, focusing on the two largest basins, the Bothnian Sea and the Baltic Proper. The non-steady state multimedia fate and transport model POPCYCLING-Baltic was employed, using recent data for PCDD/F concentrations in air and sediment as boundary conditions. The PCDD/F concentrations in water predicted by the model were in good agreement with recent measurements. The budget demonstrated that atmospheric deposition was the dominant source of PCDD/Fs to the basins as a whole. This conclusion was supported by a statistical comparison of the PCDD/F congener patterns in surface sediments from accumulation bottoms with the patterns in ambient air, bulk atmospheric deposition, and a range of potential industrial sources. Prospective model simulations indicated that the PCDD/F concentrations in the water column will continue to decrease in the coming years due to the slow response of the Baltic Sea system to falling PCDD/F inputs in the last decades, but that the decrease would be more pronounced if ambient air concentrations were to drop further in the future, for instance as a result of reduced emissions. The study illustrates the usefulness of using monitoring data and multimedia models in an integrated fashion to address complex organic contaminant issues.
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| 60. |
- Armitage, James M., 1974-
(författare)
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Modeling the global fate and transport of perfluoroalkylated substances (PFAS)
- 2009
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Perfluoroalkylated substances (PFAS) are persistent contaminants that are widely distributed in the global environment. Despite the fact that these chemicals have been manufactured and used for over 50 years, there has been little scientific and regulatory interest until very recently. An important research priority over the past decade has been to gain a better understanding of the mechanisms and pathways explaining the presence of these compounds in remote regions. One explanation is related to the use and release of volatile precursor compounds which undergo atmospheric transport and are also susceptible to degradation to PFAS through gas phase reactions with radical species. The main purpose of this doctoral thesis was to investigate an alternative explanation, namely the long-range transport (LRT) of PFAS themselves, which have been released into the environment in substantial quantities during manufacturing and product use. Papers I – III explore the LRT potential of perfluorocarboxylic acids and perfluorocarboxylates and demonstrate that both oceanic and atmospheric transport are efficient pathways of dispersion from source to remote regions of the Northern Hemisphere. Oceanic transport of perfluorooctane sulfonate (PFOS) was shown to be an important process in Paper IV as well. The role of precursor transport and degradation to PFOS was also examined in this paper. The most interesting aspect of the fate and transport of PFOS precursors is the rapid response in ambient concentrations exhibited by these compounds in the model simulations following production phase-out. Since precursor compounds are known to degrade to PFOS in vivo, the modeling results demonstrate that this exposure pathway is a plausible explanation for the declining trends in PFOS concentrations reported for marine mammals in some remote environments.
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