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Conceptual hydrological models can move towards process-oriented modelling when addressing broader issues than discharge modelling alone. For instance, water quality modelling generally requires understanding of both pathways and travel times which might not be easily identified because observations at the outlet aggregate all processes at the catchment scale. In this study we tested if adding a second kind of observation, specifically sediment data, can help distinguish overland flow from total discharge. We applied a multi-objective calibration on both discharge and suspended sediment concentration simulation performance to the World-Wide Hydrological Predictions for the Environment (HYPE) model for 111 catchments spread over the USA. Results show that in comparison to two calibrations made one after the other, the multi-objective calibration leads to a significant improvement on the simulation performance of suspended sediments without a significant impact on the performance of discharge. New modelling hypotheses for overland flow calculations are proposed and resulted in similar discharge performances as the original one but with fewer parameters, which reduces equifinality and can prevent unwarranted model complexity in data-poor areas., (© 2022 The Authors. Hydrological Processes published by John Wiley & Sons Ltd.)

Background: Chronic myeloid leukaemia is in principle a treatable malignancy but drug resistance is lowering survival. Recent drug discoveries have opened up new options for drug combinations, which is a concept used in other areas for preventing drug resistance. Two of these are (I) Axitinib, which inhibits the T315I mutation of BCR-ABL1, a main source of drug resistance, and (II) Asciminib, which has been developed as an allosteric BCR-ABL1 inhibitor, targeting an entirely different binding site, and as such does not compete for binding with other drugs. These drugs offer new treatment options., Methods: We measured the proliferation of KCL-22 cells exposed to imatinib-dasatinib, imatinib-asciminib and dasatinib-asciminib combinations and calculated combination index graphs for each case. Moreover, using the median-effect equation we calculated how much axitinib can reduce the growth advantage of T315I mutant clones in combination with available drugs. In addition, we calculated how much the total drug burden could be reduced by combinations using asciminib and other drugs, and evaluated which mutations such combinations might be sensitive to., Results: Asciminib had synergistic interactions with imatinib or dasatinib in KCL-22 cells at high degrees of inhibition. Interestingly, some antagonism between asciminib and the other drugs was present at lower degrees on inhibition. Simulations revealed that asciminib may allow for dose reductions, and its complementary resistance profile could reduce the risk of mutation based resistance. Axitinib, however, had only a minor effect on T315I growth advantage., Conclusions: Given how asciminib combinations were synergistic in vitro, our modelling suggests that drug combinations involving asciminib should allow for lower total drug doses, and may result in a reduced spectrum of observed resistance mutations. On the other hand, a combination involving axitinib was not shown to be useful in countering drug resistance.

Inland waters transport, transform and retain significant amounts of dissolved organic carbon (DOC) that may be biologically reactive (bioreactive) and thus potentially degraded into atmospheric CO 2 . Despite its global importance, relatively little is known about environmental controls on bioreactivity of DOC as it moves through river systems with varying water residence time (WRT). Here we determined the influence of WRT and landscape properties on DOC bioreactivity in 15 Swedish catchments spanning a large geographical and environmental gradient. We found that the short-term bioreactive pools (0-6 d of decay experiments) were linked to high aquatic primary productivity that, in turn, was stimulated by phosphorus loading from forested, agricultural and urban areas. Unexpectedly, the percentage of long-term bioreactive DOC (determined in 1-year experiments) increased with WRT, possibly due to photo-transformation of recalcitrant DOC from terrestrial sources into long-term bioreactive DOC with relatively lower aromaticity. Thus, despite overall decreases in DOC during water transit through the inland water continuum, DOC becomes relatively more bioreactive on a long time-scale. This increase in DOC bioreactivity with increasing WRT along the freshwater continuum has previously been overlooked. Further studies are needed to explain the processes and mechanisms behind this pattern on a molecular level.

Wastewater discharge and agricultural activities may pose microbial risks to natural water sources. The impact of different sources can be assessed by water quality modelling. The aim of this study was to use hydrological and hydrodynamic models to illustrate the risk of exposing grazing animals to faecal pollutants in natural water sources, using three zoonotic faecal pathogens as model microbes and fictitious pastures in Sweden as examples. Microbial contamination by manure from fertilisation and grazing was modelled by use of a hydrological model (HYPE) and a hydrodynamic model (MIKE 3 FM), and microbial contamination from human wastewater was modelled by application of both models in a backwards process. The faecal pathogens Salmonella spp., verotoxin-producing Escherichia coli O157:H7 (VTEC) and Cryptosporidium parvum were chosen as model organisms. The pathogen loads on arable land and pastures were estimated based on pathogen concentration in cattle faeces, herd prevalence and within-herd prevalence. Contamination from human wastewater discharge was simulated by estimating the number of pathogens required from a fictitious wastewater discharge to reach a concentration high enough to cause infection in cattle using the points on the fictitious pastures as their primary source of drinking water. In the scenarios for pathogens from animal sources, none of the simulated concentrations of salmonella exceeded the concentrations needed to infect adult cattle. For VTEC, most of the simulated concentrations exceeded the concentration needed to infect calves. For C. parvum, all the simulated concentrations exceeded the concentration needed to infect calves. The pathogen loads needed at the release points for human wastewater to achieve infectious doses for cattle were mostly above the potential loads of salmonella and VTEC estimated to be present in a 24-h overflow from a medium-size Swedish wastewater treatment plant, while the required pathogen loads of C. parvum at the release points were below the potential loads of C. parvum in a 24-h wastewater overflow. Most estimates in this study assume a worst-case scenario. Controlling zoonotic infections at herd level prevents environmental contamination and subsequent human exposure. The potential for infection of grazing animals with faecal pathogens has implications for keeping animals on pastures with access to natural water sources. As the infectious dose for most pathogens is more easily reached for calves than for adult animals, and young calves are also the main shedders of C. parvum, keeping young calves on pastures adjacent to natural water sources is best avoided.

While agricultural activities, such as the application of manure on arable land and animal grazing on pastures, provide economic and environmental benefits, they may also pose microbial risks to water sources. The aim of this paper was to study the microbial fate and transport in an agricultural catchment and recipient water source through further development of the hydrological model HYPE. Hydrological modelling was combined with hydrodynamic modelling to simulate the fate and transport of Salmonella spp., verotoxin-producing Escherichia coli O157:H7 (VTEC) and Cryptosporidium parvum in an agricultural catchment of a drinking water source, Lake Vombsjön, in Sweden. This approach was useful to study the influence of different processes on the pathogen fate and transport, and to interpret the relative changes in the simulated concentrations. Sensitivity analysis indicated that the largest uncertainties in the model were associated with the estimation of pathogen loads, parameterisation of the pathogen processes, and simulation of partitioning between surface runoff and infiltration. The proposed modelling approach is valuable for assessing the relative effect of different risk-reducing interventions.

Procedures for source apportionment of nutrients transported in rivers and streams are often uncertain and difficult to validate. In this study, we investigated if the oxygen isotope ratios in stream dissolved phosphate (δ 18 O P ) can be used to distinguish between the phosphorus (P) originating from agricultural runoff and from rural sewage, at different periods of the year. Water was collected from septic tanks, drainage wells and the stream outlet in a small (7.3 km 2 ) agricultural catchment to capture variations in the isotope signature at different flow events. The δ 18 O P signature in septic tank effluent (+13.2 to +14.5‰) was significantly different from that in drainage water (+9.0 to +15.7‰). Four different septic tanks had surprisingly similar isotope signature when 24 h composite samples were collected. Most of the water samples were not in oxygen isotope equilibrium. In three drainage wells, the δ 18 O P signature varied from +7.8 up to +15.7‰ with higher values in periods with a larger contribution of superficial streamflow generation. A rainfall soon after manure had been spread resulted in a δ 18 O P of 15.7‰ in a drainage well, and was also reflected in a similar value at the catchment outlet. This implies that the source isotope signal may be conserved during moderate or high flows. A three end-member model including the geological background would be a useful start to quantify the P contribution from diverse sources. Temporal differences in biological activity and the predominant transport pathways through soil profiles must be considered along with information about fertilisation. In combination with hydrological modelling of water pathways, this may considerably improve our understanding of catchment P losses., (Copyright © 2017 Elsevier B.V. All rights reserved.)

River flow is mainly controlled by climate, physiography and regulations, but their relative importance over large landmasses is poorly understood. Here we show from computational modelling that hydropower regulation is a key driver of flow regime change in snow-dominated regions and is more important than future climate changes. This implies that climate adaptation needs to include regulation schemes. The natural river regime in snowy regions has low flow when snow is stored and a pronounced peak flow when snow is melting. Global warming and hydropower regulation change this temporal pattern similarly, causing less difference in river flow between seasons. We conclude that in snow-fed rivers globally, the future climate change impact on flow regime is minor compared to regulation downstream of large reservoirs, and of similar magnitude over large landmasses. Our study not only highlights the impact of hydropower production but also that river regulation could be turned into a measure for climate adaptation to maintain biodiversity on floodplains under climate change.Global warming and hydropower regulations are major threats to future fresh-water availability and biodiversity. Here, the authors show that their impact on flow regime over a large landmass result in similar changes, but hydropower is more critical locally and may have potential for climate adaptation in floodplains.

Uptake of polychlorinated dibenzo-p-dioxins and polychlorinated dibenzofurans (PCDD/Fs) was studied in earthworms collected from a sawmill site in Sweden with severe PCDD/Fs contamination (the hot spot concentration was 690,000ng TEQ WHO2005 /kg d.w.) in order to investigate the transfer of PCDD/Fs from the site to the biota. PCDD/Fs concentrations in the collected earthworms were compared to PCDD/Fs concentrations in laboratory exposed earthworms (Eisenia fetida), which were exposed to contaminated soils from the sawmill site for 34days. All analyses were performed by high resolution gas chromatography/high resolution mass spectrometry (HRGC/HRMS). PCDD/Fs concentrations in the earthworms ranged from 290 to 520,000pg/g (f.w.). The main congeners found in both soils and earthworms were OCDF, 1234678-HpCDF, OCDD and 1234678-HpCDD. The study showed that the PCDD/Fs in the soil were biovailable to the earthworms and the PCDD/Fs concentrations in the soils correlated with the concentrations in the earthworms. Earthworm samples from soil with lower concentration had higher bioaccumulation factors than samples from soils with high concentration of contamination. Thus, a less contaminated soil could yield higher concentrations in earthworms compared to a higher contaminated soil. Assuming that when assessing risks with PCDD/F contaminated soil, a combination of chemical analysis of soil PCDD/Fs concentrations and bioavailability should be employed for a more comprehensive risk assessment., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Per- and polyfluoroalkyl substances (PFASs) are a class of compounds with unique chemical properties that have been shown useful in a wide variety of applications because they provide materials with reduced surface tension and exceptional non-stick properties. PFASs are commonly found in impregnation materials, coatings of papers and textiles, fire-fighting foams, pesticides, and cleaning agents. The potential for human exposure to PFASs is high because of their widespread distribution. The aim of this study was to investigate levels of PFASs in men and women from Sweden and to assess the influence of gender and parity among women. Levels of 13 PFASs were determined in plasma samples collected during 2001-2004 from 1016 (507 women) 70year-old participants from the population-based Prospective Study of the Vasculature in Uppsala Seniors (PIVUS). The PFASs studied were nine perfluorinated carboxylic acids (PFCAs), four perfluorinated sulfonic acids (PFSAs) and perfluorooctane sulfonamide (PFOSA). In addition, structural isomers of perfluorooctane sulfonic acid (PFOS) were determined in a subset of 398 individuals. The detection rates were high and the majority of the studied compounds were detected in more than 75% of the participants. Levels of the selected analytes were found to be similar to other studies of non-occupationally exposed populations. Gender differences were observed in levels of PFHpA which was higher in men, while PFHxS was higher in women. Parity among women was shown to have a minor effect on PFAS concentrations and we found primi- and multiparous women to have slightly lower levels of PFUnDA when compared to nulliparous women., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Advances in process-based modelling of loads of nitrogen and phosphorus carried by rivers have created new possibilities to interpret time series of water quality data. We examined how model runs with constant anthropogenic forcing can be used to estimate and filter out weather-driven variation in observational data and, thereby, draw attention to other features of such data. An assessment of measured and modelled nutrient concentrations at the outlets of 45 Swedish rivers provided promising results for total nitrogen. In particular, joint analyses of observational data and outputs from the catchment model S-HYPE strengthened the evidence that downward trends in nitrogen were due to mitigation measures in agriculture. Evaluation of modelled and observed total phosphorus concentrations revealed considerable bias in the collection or chemical analysis of water samples and also identified weaknesses in the model outputs. Together, our results highlight the need for more efficient two-way communication between environmental modelling and monitoring.

Polychlorinated dibenzo-p-dioxins and polychlorinated dibenzo-p-furans (PCDD/Fs) were analysed in soil from a Swedish sawmill site where chlorophenols (CPs) had been used more than 40 years ago. The most contaminated area at the site was the preservation subarea where the PCDD/F WHO2005-TEQ level was 3450 times higher than the current Swedish guideline value of 200 ng TEQ/kg soil for land for industrial use. It was also shown that a fire which destroyed the sawmill might have affected the congener distribution at the concerned areas. To get a broader picture of the contamination both GIS (spatial interpolation analysis) and multivariate data analysis (PCA) were applied to visualize and compare PCDD/F levels as well as congener distributions at different areas at the site. It is shown that GIS and PCA are powerful tools in decisions on future investigations, risk assessments and remediation of contaminated sites., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

To facilitate high-throughput analysis suitable for large epidemiological studies we developed an automated column-switching ultra-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method for determination of perfluorocarboxylic acids (PFCAs; C5, C6, C7, C8, C9, C10, C11, C12, and C13), perfluoroalkyl sulfonic acids (PFSAs; C4, C6, C8, and C10), perfluorooctane sulfonamide (PFOSA), and five groups of structural perfluorooctane sulfonic acid (PFOS) isomers in human serum or plasma. The analytical procedure involves rapid protein precipitation using 96-well plates followed by an automated sample clean-up using an on-line trap column removing many potentially interfering sample components while through the mobile phase gradient the target analytes are eluted onto the analytical column for further separation and subsequent mass detection. The method was linear (R(2)<0.995) at concentrations ranging from 0.01 to 60ngmL(-1) with method detection limits ranging between 0.01 and 0.17ngmL(-1) depending on the analyte. The developed method was precise, with repeatability (n=7) and reproducibility (n=103) coefficients of variation between 2% and 20% for most compounds including PFOS (2% and 8%) and its structural isomers (2-6% and 4-8%). The method was in conformity with a standard reference material. The column-switching HPLC-MS/MS method has been successfully applied for the determination of perfluoroalkyl substances including structural PFOS isomers in human plasma from an epidemiological study., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Previous reports show that professional ski waxers have elevated blood levels of perfluorinated substances (PFAS) such as perfluorooctanoate (PFOA) and are exposed to very high concentrations of PFAS in air during ski waxing. Aerosol exposure increases the risk of cardiovascular disease, and PFOA is a potential hormonal disruptor and carcinogen, and can affect the fatty acid metabolism. Animal studies have shown that 8:2 FTOH can undergo biotransformation to PFOA. For the first time, this study presents an occupational scenario of professional ski waxers who are exposed to extremely high dust levels as well as per- and polyfluorinated compounds. Personal and fixed measurements of total aerosol, inhalable and respirable fractions were performed during World Cup events 2007-2010. The occupational exposure limit (OEL) is exceeded in 37% of the personal measurements with concentrations up to 15 mg m(-3) in air. There are differences between personal and area total aerosol concentrations with levels from personal measurements twice as high as those from the area measurements. The personal levels for FTOH ranged up to 996 μg m(-3) (mean = 114 μg m(-3)) and for PFOA up to 4.89 μg m(-3) (mean = 0.53 μg m(-3)) in ENV+ sorbent samples as compared to the general exposure levels from air reaching only low ng m(-3) (<30 ng m(-3)) levels. FTOHs were not detected in aerosols but PFOA showed an average level of 12 μg m(-3) (range = 1.2-47 μg m(-3)). The ski waxers' exposure to paraffin fumes and PFAS is not in compliance with the occupational exposure standards and by far exceed the general populations' exposure. Preventive measures must be taken to minimize the exposure in this occupational group.

Levels of perfluorocarboxylates (PFCAs) in biological compartments have been known for some time but their transport routes and distribution patterns are not properly elucidated. The opinions diverge whether the exposure of the general population occurs indirect through precursors or direct via PFCAs. Previous results showed that ski wax technicians are exposed to levels up to 92 000 ng/m(3) of 8:2 fluorotelomer alcohol (FTOH) via air and have elevated blood levels of PFCAs. Blood samples were collected in 2007-2011 and analyzed for C(4)-C(18) PFCAs, 6:2, 8:2 and 10:2 unsaturated fluorotelomer acids (FTUCAs) and 3:3, 5:3 and 7:3 fluorotelomer acids (FTCAs) using UPLC-MS/MS. Perfluorooctanoic acid (PFOA) was detected in levels ranging from 1.90 to 628 ng/mL whole blood (wb). Metabolic intermediates 5:3 and 7:3 FTCA were detected in all samples at levels up to 6.1 and 3.9 ng/mL wb. 6:2, 8:2 and 10:2 FTUCAs showed maximum levels of 0.07, 0.64 and 0.11 ng/mL wb. Also, for the first time levels of PFHxDA and PFOcDA were detected in the human blood at mean concentrations up to 4.22 ng/mL wb and 4.25 ng/mL wb respectively. The aim of this study was to determine concentrations of PFCAs and FTOH metabolites in blood from ski wax technicians., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Persistent Organic Pollutants (POPs) are a huge group of chemicals that have been linked to various adverse health effects in humans. Large epidemiological studies investigating gender differences in levels of POPs in the elderly are limited and the results from these are not always consistent. The present study was undertaken to examine the background levels of a broad range of POPs in human plasma samples among elderly men and women from Sweden and to assess the influence of gender. Levels of 23 POPs were determined in plasma samples collected during 2001-2004 from 1016 (50.2% women) 70year-old participants from the population-based Prospective Study of the Vasculature in Uppsala Seniors (PIVUS). Measurements were performed using high resolution gas chromatography with high resolution mass spectrometry (HRGC-HRMS) and the POPs studied were 16 polychlorinated biphenyls (PCBs), five organochlorine (OC) pesticides, one dioxin, and one brominated flame retardant. The concentrations of the selected POPs were found similar, or comparable, to other studies of non-occupationally exposed populations from Sweden and Europe. Differences in levels of POPs between men and women were assessed by using Wilcoxon rank-sum (Mann-Whitney) test. Significant (p<0.0001) gender differences in levels of specific POPs were observed and a number of POP concentrations were found to differ between men and women. More specifically, levels of HCB, OCDD, and PCB congeners #74, #105, and #118 were found to be higher in women, while the rest of the majority of POPs were higher in men., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

A rapid analytical screening method allowing simultaneous analysis of 23 persistent organic pollutants (POPs) in human plasma was developed. Sample preparation based on solid-phase extraction (SPE) with additional clean-up using small multilayer silica gel columns. SPE was performed using a custom made polystyrene-divinylbenzene sorbent for the extraction of chlorinated and brominated POPs. Special efforts to reduce sample volume and improve speed and efficiency of the analytical procedure were made. Determination of 16 polychlorinated biphenyls (PCBs), 5 organochlorine (OC) pesticides, octachlorinated dibenzo-p-dioxin (OCDD) and polybrominated diphenyl ether (BDE #47) in 0.5 mL human plasma was performed by using high resolution gas chromatography coupled to high resolution mass spectrometry (HRGC/HRMS). Recovery of POPs ranged between 46% and 110%, and reproducibility was below 25% relative standard deviation (RSD) for all target compounds, except for trans-nonachlor and OCDD, which were present only at low levels. Limits of detection (LOD) were for the PCBs between 0.8 and 117.7 pg mL(-1) plasma and for the OC pesticides between 5.9 and 89.1 pg mL(-1) plasma. The LOD for OCDD and BDE #47 were 1.4 pg mL(-1) plasma, and 9.2 pg mL(-1) plasma, respectively. The presented method was successfully applied to 1016 human plasma samples from an epidemiological study on cardiovascular disease., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

A total of 27 per- and polyfluorinated compounds (PFCs) were determined in both house dust (n=10) and indoor air (n=10) from selected homes in Catalonia, Spain. Concentrations were found to be similar or lower than those previously reported for household microenvironments in other countries. Ten PFCs were detected in all house dust samples. The highest mean concentrations corresponded to perfluorodecanoic acid (PFDA) and perfluorononanoic acid (PFNA), 10.7 ng/g (median: 1.5 ng/g) and 10.4 ng/g (median: 5.4 ng/g), respectively, while the 8:2 fluorotelomer alcohol (FTOH) was the dominating neutral PFC at a concentration of 0.41 ng/g (median: 0.35 ng/g). The indoor air was dominated by the FTOHs, especially the 8:2 FTOH at a mean (median) concentration of 51 pg/m(3) (median: 42 pg/m(3)). A limited number of ionic PFCs were also detected in the indoor air samples. Daily intakes of PFCs were estimated for average and worst case scenarios of human exposure from indoor sources. For toddlers, this resulted in average intakes of ∑ionic PFCs of 4.9ng/day (0.33 ng/kg(bw)/day for a 15 kg toddlers) and ∑neutral PFCs of 0.072 ng/day (0.005 ng/kg(bw)/day) from house dust. For adults, the average daily intakes of dust were 3.6 and 0.053 ng/day (0.05 and 0.001 ng/kg(bw)/day for a 70 kg adult) for ∑ionic and ∑neutral PFCs, respectively. The average daily inhalation of ∑neutral PFCs was estimated to be 0.9 and 1.3 ng/day (0.06 and 0.02 ng/kg(bw)/day) for toddlers and adults, respectively. For PFOS, the main ionic PFC detected in indoor air samples, the median intakes (based on those samples where PFOS was detected), resulted in indoor exposures of 0.06 and 0.11 ng/day (0.004 and 0.002 ng/kg(bw)/day) for toddlers and adults, respectively. Based on previous studies on dietary intake and drinking water consumption, both house dust and indoor air contribute significantly less to PFC exposure within this population., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Levels of perfluorinated carboxylates (PFCAs) in different environmental and biological compartments have been known for some time, but the routes of exposure still remain unclear. The opinions are divergent whether the exposure to general populations occurs mainly indirect through precursor compounds or direct via PFCAs. Previous results showed elevated blood levels of PFCAs in ski wax technicians compared to a general population. The objective of this follow-up study was to determine concentrations of PFCAs, perfluorosulfonates (PFSAs), and fluorotelomer alcohols (FTOHs), precursor compounds that are known to degrade to PFCAs, in air collected in the breathing zone of ski wax technicians during work. We collected air samples by using ISOLUTE ENV+ cartridges connected to portable air pumps with an air flow of 2.0 L min(-1). PFCAs C5-C11 and PFSAs C4, C6, C8, and C10 were analyzed using LC-MS/MS and FTOHs 6:2, 8:2, and 10:2 with GC-MS/MS. The results show daily inhalation exposure of 8:2 FTOH in μg/m(3) air which is up to 800 times higher than levels of PFOA with individual levels ranging between 830-255000 ng/m(3) air. This suggests internal exposure of PFOA through biotransformation of 8:2 FTOH to PFOA and PFNA in humans.

Perfluorinated compounds (PFCs) have been determined in 21 samples of selected food and beverages such as meat, fish, bread, vegetables, milk, drinking water and tea from the Norwegian marked. Up to 12 different PFCs were detected in the samples. Perfluorooctanoic acid (PFOA) and perfluorooctane sulfonic acid (PFOS) were found in concentrations similar to or lower than what has been observed in other studies world-wide. Differences in the relative proportion of PFOA and PFOS between samples of animal origin and samples of non-animal origin were observed and support findings that PFOS has a higher bioaccumulation potential in animals than PFOA. Based on these 21 measurements and consumption data for the general Norwegian population, a rough estimate of the total dietary intake of PFCs was found to be around 100 ng d(-1). PFOA and PFOS contributed to about 50% of the total intake. When dividing the population in gender and age groups, estimated intakes were decreasing with increasing age and were higher in males than females. The estimated intakes of PFOS and PFOA in the present study are lower than what has been reported in studies from Spain, Germany, United Kingdom, Canada and Japan. This study illustrates that by improving the analytical methods for determination of PFC in food samples, a broad range of compounds can be detected, which is important when assessing dietary exposure., (Copyright (c) 2010 Elsevier Ltd. All rights reserved.)

A time trend study focusing on ski waxing technicians' exposure to perfluorinated chemicals (PFCs) from fluorinated wax fumes was performed in 2007/2008. Levels of eight perfluorocarboxylates and three perfluorosulfonates were analyzed in monthly blood samples from eight technicians. Samples were collected before the ski season, i.e., preseason, then at four FIS World Cup competitions in cross country skiing, and finally during an unexposed 5-month postseason period. The perfluorinated carboxylates perfluoroheptanoic acid (PFHpA), perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA), and perfluoroundecanoic acid (PFUnDA) bioaccumulate, and continued exposure may contribute to elevated levels in ski technicians compared to the general population. The wax technicians' median blood level of PFOA is 112 ng/mL compared to 2.5 ng/mL in the general Swedish population. A significant correlation was found between number of working years and levels of perfluorocarboxylates. The PFOA levels in three technicians with "low" initial levels of PFOA (<10.0 ng/mL in preseason blood) increased by 254, 134, and 120%, whereas five technicians with "high" initial levels (>100 ng/mL in preseason sample) were at steady state. PFHxA is suggested to have a short half-life in humans relative the other perfluorocarboxylates. The levels of perfluorosulfonates were unaffected by the wax exposure.

Background, Aim and Scope: Perfluorinated compounds (PFCs) are global environmental pollutants that bioaccumulate in wildlife and humans. Laboratory experiments have revealed toxic effects such as delayed development, humoral suppression, and hepatotoxicity. Although numerous human blood levels have been reported, little is known about distribution in the human body. Knowledge about PFC distribution and accumulation in the human body is crucial to understanding uptake and subsequent effects as well as to conduct risk assessments. The present study reports PFC levels in human liver and breast milk from a general population living in Catalonia, Spain. Liver and milk levels are compared to previously reported levels in blood from the same geographic area as well as to other existing reports on human liver and milk levels in other countries., Materials and Methods: Human liver (n = 12) and milk (n = 10) samples were collected in 2007 and 2008 in Catalonia, Spain. Liver samples were taken postmortem from six males and six females aged 27-79 years. Milk samples were from healthy primipara women (30-39 years old). Both liver and milk were analyzed by solid-phase extraction and ultra-performance liquid chromatography tandem mass spectrometry., Results: Six PFCs were detected in liver, with perfluorooctanesulfonate (PFOS, 26.6 ng/g wet weight) being the chemical with the highest mean concentration. Other PFCs such as perfluorohexanesulfonate (PFHxS), perfluorooctanoic acid (PFOA), and acids with chain lengths up to C11 were also detected, with mean levels ranging between 0.50 and 1.45 ng/g wet weight. On the other hand, PFOS and PFHxS were the only PFCs detected in human milk, with mean concentrations of 0.12 and 0.04 ng/mL, respectively., Discussion: While milk concentrations were similar to reported levels from other countries, liver samples contained more PFCs above quantification limits and higher PFOS concentrations compared to the only two other reports found in the literature. Differences between the results of the present study and those concerning previous investigations can be due to declining levels of some PFCs, which have been reported for the USA. The relationship between PFC concentrations in human liver, milk, and blood was assessed using blood concentrations previously determined in Catalonia. Those levels resulted in liver/serum ratios of 1.7:1, 1.4:1, and 2.1:1 for PFOS, perfluorodecanoic acid, and perfluoroundecanoic acid, respectively. Accumulation in liver is suggested for PFOS and the perfluorocarboxylic acids with carbon chain lengths C9, C10, and C11. For PFOA and PFHxS, fivefold and 14-fold higher concentrations, respectively, were seen in serum as compared to liver. The mean concentration of PFOS and PFHxS in milk was only 0.8% and 0.6% of the reported mean serum level, respectively., Conclusions: The results of the present study show that several PFCs could be detected in human liver samples of subjects living in Tarragona. Concerning human milk, the mechanism by which PFCs are transferred from mother's blood to breast milk is still unclear. Considering that PFCs are strongly bound to the protein fraction in blood, the possibility of PFCs entering the milk and accumulating to levels observed in maternal plasma is limited., Recommendations and Perspectives: Interestingly, the potential accumulation difference for PFCs with different chain lengths might be of great importance for risk assessment. Continuing studies on the distribution of different PFCs in human tissue are therefore justified.

Polybrominated dibenzo-p-dioxins and dibenzofurans (PBDD/Fs) were analyzed in both human adipose tissue and plasma from nine individuals, from the Swedish general population, using high resolution gas chromatography/high resolution mass spectrometry (HRGC/HRMS). In addition, several other persistent organic pollutants (POPs) were determined in the same samples, including polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs), polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs) and perfluorinated chemicals (PFCs). Polybrominated dibenzofurans were detected in all of the human adipose tissue samples confirming their presence in the Swedish population. The highest concentration was found for 2,3,7,8-TeBDF, ranging from 0.27 to 2.4 pg g(-1) lipid, followed by 1,2,3,7,8-PeBDF, 0.23-0.89pgg(-1) lipid, 2,3,4,7,8-PeBDF, 0.44-0.54 pg g(-1) lipid, and 2,7/2,8-DiBDF, 0.19-0.30 pg g(-1) lipid. No PBDDs could be detected above the limit of detection (<0.02-<0.21 pg g(-1) lipid) in any of the samples. The levels of PCDD/Fs were in the range 1.79-31.5pg toxic equivalents (TEQ)g(-1) lipid, and PBDEs were found in the 1.16-7.46 ng g(-1) lipid range. The measured chlorinated dioxins indicate decreasing human concentrations in Sweden. The toxicity equivalents (TEQ) for PBDD/Fs (0.2-0.8 pg TEQg(-1) lipid) were found to contribute 1-15% of the total dioxin TEQ of the chlorinated dioxins and furans (5-18 pg TEQg(-1) lipid) depending on the individual. Also PBDEs concentrations are decreasing compared to 1997-2000, but most noteworthy a shift in BDE pattern where BDE#47 is surpassed by BDE#153. The levels of PFCs are in the same range as the highest levels of the traditional POPs (sum of 60 PCBs) based on volume. These findings illustrate the importance of continuous monitoring of brominated compounds in both human and the environment.

In this study, the concentrations of 13 perfluorinated compounds (PFCs) (PFBuS, PFHxS, PFOS, THPFOS, PFHxA, PFHpA, PFOA, PFNA, PFDA, PFUnDA, PFDoDA, PFTDA, and PFOSA) were analyzed in municipal drinking water samples collected at 40 different locations from 5 different zones of Catalonia, Spain. Detection limits ranged between 0.02 (PFHxS) and 0.85 ng/L (PFOA). The most frequent compounds were PFOS and PFHxS, which were detected in 35 and 31 samples, with maximum concentrations of 58.1 and 5.30 ng/L, respectively. PFBuS, PFHxA, and PFOA were also frequently detected (29, 27, and 26 samples, respectively), with maximum levels of 69.4, 8.55, and 57.4 ng/L. In contrast, PFDoDA and PFTDA could not be detected in any sample. The most contaminated water samples were found in the Barcelona Province, whereas none of the analyzed PFCs could be detected in two samples (Banyoles and Lleida), and only one PFC could be detected in four of the samples. Assuming a human water consumption of 2 L/day, the maximum daily intake of PFOS and PFOA from municipal drinking water would be, for a subject of 70 kg of body weight, 1.7 and 1.6 ng/kg/day. This is clearly lower than the respective Tolerable Daily Intake set by the European Food Safety Authority. In all samples, PFOS and PFOA also showed lower levels than the short-term provisional health advisory limit for drinking water (200 ng PFOS/L and 400 ng PFOA/L) set by the US Environmental Protection Agency. Although PFOS and PFOA concentrations found in drinking water in Catalonia are not expected to pose human health risks, safety limits for exposure to the remaining PFCs are clearly necessary, as health-based drinking water concentration protective for lifetime exposure is set to 40 ng/L for PFOA.

Exposure to some pesticides and persistent organic pollutants (POPs) has been indicated to be a risk factor for non-Hodgkin's lymphoma (NHL). Epstein-Barr virus (EBV) has been associated with some subgroups of NHL. In a previous study we found an interaction between high concentrations of some POPs and titres of antibodies to EBV early antigen (EA IgG) in relation to NHL. In the present study we measured lipid adjusted plasma concentrations of 35 congeners of polychlorinated biphenyls (PCB), p,p'-dichlorodiphenyldichloroethyelene (p,p'-DDE), hexachlorobenzene (HCB), seven subgroups of chlordanes (cis-heptachlorepoxide, cis-chlordane, trans-chlordane, oxychlordane, MC6, trans-nonachlordane, cis-nonachlordane) and one polybrominated diphenylether (PBDE) congener (no. 47) in 99 cases with NHL and 99 population based controls. Odds ratios (OR) for NHL were estimated. Sum of PCBs > median in the controls gave odds ratio (OR) 2.0, 95% confidence interval (CI) 0.99-3.9. High sum of chlordanes yielded OR 2.3, 95% CI 1.2-4.5. An interaction with EBV EA IgG was found. High sum of PCB gave OR 5.2, 95% CI 1.9-14 in the group with EA IgG > 40. Similarly HCB yielded OR 5.3, 95% CI 1.9-15, pp'-DDE gave OR 3.3, 95% CI 1.4-7.7 and sum of chlordanes yielded OR 6.8, 95% CI 2.3-20, whereas no association was found with PBDE. In summary, this study confirmed an association between certain POPs and NHL with an interaction with titre of IgG antibody to EBV EA.

Perfluorinated chemicals (PFCs) are analyzed in laboratories worldwide to determine human blood levels and exposure pathways. The development of the analytical technique has been rapid in the last 10 years, and prerequisites for accurate and precise determination of PFCs in human blood at low ng/g concentrations are today readily available. The main contributing factors are the improved LC-MS instrumentations, the increased availability of native and mass labeled PFC standards, and new column materials available for chromatographic separations. The results of the first international interlaboratory study (ILS) in 2005 on PFCs revealed relatively better analytical results for human blood analyses when compared to analyses of a number of environmental matrices. The representative accuracy for the analyses of PFCs in human matrixes reported in recent years was established in the second human serum ILS in 2006. Interlaboratory standard deviations for the two human serum samples one low level concentration and one medium level concentration were found to be 12% and 16% for PFOS, respectively, and 47% and 21% for PFOA, respectively. Reported detections for all PFCs followed a frequency of PFOS>PFOA>PFHxS>PFNA>PFDA>>PFDoA>>PFDS>>PFHxA. Due to the small number of reported values for the other perfluorosulfonates and perfluorocarboxylates, standard deviations were not established.

Background, Aim, and Scope: In recent years, due to a high persistence, biomagnification in food webs, presence in remote regions, and potential toxicity, perfluorochemicals (PFCs) have generated a considerable interest. The present study was aimed to determine the levels of perfluorooctane sulfonate (PFOS), perfluorooctanoic acid (PFOA), and other PFCs in drinking water (tap and bottled) and river water samples from Tarragona Province (Catalonia, Spain)., Materials and Methods: Municipal drinking (tap) water samples were collected from the four most populated towns in the Tarragona Province, whereas samples of bottled waters were purchased from supermarkets. River water samples were collected from the Ebro (two samples), Cortiella, and Francolí Rivers. After pretreatment, PFC analyses were performed by HPLC-MS. Quantification was done using the internal standard method, with recoveries between 68% and 118%., Results: In tap water, PFOS and PFOA levels ranged between 0.39 and 0.87 ng/L (0.78 and 1.74 pmol/L) and between 0.32 and 6.28 ng/L (0.77 and 15.2 pmol/L), respectively. PFHpA, PFHxS, and PFNA were also other detected PFCs. PFC levels were notably lower in bottled water, where PFOS could not be detected in any sample. Moreover, PFHpA, PFHxS, PFOA, PFNA, PFOS, PFOSA, and PFDA could be detected in the river water samples. PFOS and PFOA concentrations were between <0.24 and 5.88 ng/L (<0.48 and 11.8 pmol/L) and between <0.22 and 24.9 ng/L (<0.53 and 60.1 pmol/L), respectively., Discussion: Assuming a human water consumption of 2 L per day, the daily intake of PFOS and PFOA by the population of the area under evaluation was calculated (0.78-1.74 and 12.6 ng, respectively). It was found that drinking water might be a source of exposure to PFCs as important as the dietary intake of these pollutants., Conclusions: The contribution of drinking water (tap and bottled) to the human daily intake of various PFCs has been compared for the first time with data from dietary intake of these PFCs. It was noted that in certain cases, drinking water can be a source of exposure to PFCs as important as the dietary intake of these pollutants although the current concentrations were similar or lower than those reported in the literature for surface water samples from a number of regions and countries., Recommendations and Perspectives: Further studies should be carried out in order to increase the knowledge of the role of drinking water in human exposure to PFCs.

Human breast milk samples from primipara women from Northern (Tromsø) (N=10) and Southern Norway (Oslo) (N=19) collected in 2000-2001 were analysed with respect to hexachlorobenzene (HCB), hexachlorocyclohexane (HCHs), chlordanes (CHLs), DDTs, mirex, toxaphenes (CHBs), polychlorinated biphenyls (PCBs), polybrominated diphenylethers (PBDEs) and hexabromocyclododecane (HBCD). CHBs, PBDEs and HBCD were only analysed in the Tromsø samples. Sum-PCBs and sum-DDTs were the major organochlorines (OCs) (170 and 110 ng g(-1) lipid weight (lw), respectively). Other OCs were found in levels of approximately 10- to 300-fold lower than sum-PCBs. Overall, the concentrations of OCs followed the decreasing order of PCBs>DDTs>HCB>HCHs approximately CHLs>CHBs>mirex. Concentrations of sum-HCHs were significantly higher in breast milk from Oslo compared to Tromsø (p<0.05). The PCB profile was dominated by PCB-153, -138 and -180. The PBDE pattern was dominated by PBDE-47 and PBDE-153. The median level of sum-PBDEs was 4.1 ng g(-1) lw. PBDE-209 was detected in all analysed samples (median 0.13 ng g(-1) lw). The estimated daily intake (EDI) for the median (range) of sum mono-ortho (mo) PCBs(8) was 3.7 (1-9) pg TEQ kg(-1) body weight per day for breast fed infants in Norway. This exceeded the TDI by a factor of 1.8 (1-4) based only on intake of mono-ortho PCBs. The present study shows that concentrations of OCs in primipara breast milk have decreased 50-60% since 1991, and that this trend is continuing.

Within the framework of a United Nations Environment Programme (UNEP) Capacity Building Project for training of laboratory staff in developing countries on persistent organic pollutant (POP) analysis, an interlaboratory study was organised following an initial evaluation of the performance of laboratories (reality check) and a series of training sessions. The target compounds were polychlorinated biphenyls (PCB) and organochlorine pesticides (OCP). Seven laboratories from five countries (Ecuador, Uruguay, Kenya, Moldova, and Fiji) participated. Most of the laboratories had no experience in determining PCBs. Although chromatograms improved considerably after the training and installation of new gas chromatographic (GC) columns at participating laboratories, the level of performance in the interlaboratory study was essentially on par with the moderate performance level achieved by European POP laboratories in the 1980s. Only some individual results were within +/-20% of the target values. The relative standard deviations (R.S.D.s) in POP concentrations determined by laboratories in a sediment sample were >200% in a number of cases. The results for a certified herring sample were better with at least some R.S.D. values below 50% and most below 100%. Clean up was as one of the main sources of error. After inspection it was ascertained that training of laboratory staff and investments in simple consumables such as glassware and GC columns would help to improve the quality of the analysis more than major investments in expensive instrumentation. Creating an effective network of POP laboratories at different continents together with a series of interlaboratory studies and workshops is suggested to improve the measurements of POPs in these countries.

The aim of this study was to determine the dietary intake of perfluorinated chemicals (PFCs) by the population of Tarragona County (Catalonia, Spain). PFC levels were determined in 36 composite samples of foodstuffs randomly purchased in various locations. Exposure to PFCs through the diet was estimated for various age/gender groups. Perfluorooctane sulfonate (PFOS), perfluorocarboxylate perfluorooctanoate (PFOA), and perfluoroheptanoic acid (PFHpA) were the only detected PFCs in foodstuffs. On average, for a standard adult man (70 kg of body weight), the dietary intake of PFOS was estimated to be 62.5 or 74.2 ng/day (assuming ND=0 or ND=1/2 LOD, respectively). Fish, followed by dairy products and meats, were the main contributors to PFOS intake. For an adult man, the intake of PFOS (1.07 ng/kg/day) and those of PFOA and PFHpA were lower than that recently reported for Canada (4.0 ng/kg/day), and considerably lower than that previously found in the United Kingdom, the only two countries where, to date, results concerning this issue have been reported. A correlation between dietary intake and blood levels of PFOS is suggested. However, the current results do not justify dietary intake as the main route of exposure governing blood concentrations of other PFCs.

Electromagnetic hypersensitivity (EHS) is used for a variety of subjective symptoms related to exposure to electromagnetic fields (EMF). The aim of this pilot study was to analyze the concentrations of certain persistent organic pollutants (POPs) in subjects with self-reported EHS. In total, 13 EHS subjects and 21 controls were included, all female. The concentration of several POPs was higher in EHS subjects than in controls. Lower concentrations were found for hexachlorobenzene and two types of chlordanes. The only significantly increased odds ratios (ORs) were found for polybrominated diphenyl ether (PBDE) #47 yielding OR=11.7, 95% confidence interval (CI)=1.45-94.7 and the chlordane metabolite MC6 with OR=11.2, 95% CI=1.18-106. The results were based on low numbers and must be interpreted with caution. This hypothesis generating study indicates the necessity of a larger investigation on this issue.

We analysed adipose tissue concentrations of persistent organic pollutants (POPs) in 21 cases with exocrine pancreatic cancer. The comparison group consisted of 59 subjects. Significantly increased concentrations of polychlorinated biphenyls (PCBs), hexachlorobenzene (HCB), sum of chlordanes and polybrominated diphenylethers (PBDEs) were found in the cases. For 1,1,-dichloro-2,2-bis(p-chlorophenyl)-ethylene (p,p'-DDE) no significant difference was seen. For PCBs no odds ratio (OR) could be calculated since all cases had concentration>median in controls used as a cut-off. HCB yielded OR=53.0, 95% confidence interval (CI)=4.64-605 and sum of chlordanes OR=18.4, 95% CI=2.71-124 whereas OR was not significantly increased for p,p'-DDE or PBDEs. Body mass index (BMI) at the time of tissue sampling was significantly lower for the cases. This might have influenced the results. Using BMI one year previously or decreasing the concentrations of POPs with the same percentage as weight loss among the cases did not change the results. Survival of the cases was shorter in the group with the concentration of POPs>median among cases, significantly so for the sum of PCBs (147 vs. 294 days), p,p'-DDE (134 vs. 302 days), and sum of chlordanes (142 vs. 294 days) in the high and low group, respectively. The results were based on a low number of cases and should be interpreted with caution.

Human serum and plasma from Sweden (n=17), the United Kingdom (the UK) (n=13) and Australia (n=40) were analyzed by high performance liquid chromatography coupled to mass spectrometry. The objective was to identify different perfluorooctane sulfonate (PFOS) isomers. Similar isomer patterns typical for the electrochemical fluorination (ECF) process were found for all samples. The linear PFOS (L-PFOS) was the major isomer found (58-70%) followed by the monosubstituted PFOS isomers 1/6-CF(3)-PFOS (18-22%) and 3/4/5-CF(3)-PFOS (13-18%). Disubstituted isomers were also detected. The percentage of L-PFOS found in the serum and plasma samples was lower compared to a standard PFOS product (76-79%). The pattern of PFOS isomers in human serum and plasma may be suggestive concerning potential isomeric discrimination since PFOS is only produced by ECF. Possibilities for such isomer discrimination are discussed. Significant higher content of L-PFOS (68%) in Swedish samples compared to Australia and the UK (59%) was also found, which may suggest differences in exposure sources for humans.

Fluorinated organic compounds (FOCs) are a group of chemicals widely used as surfactants, lubricants, polymers, and fire-fighting foams. Recent studies have shown the ubiquitous distribution of FOCs in the environment, wildlife, and humans. We here report the results of a pilot study conducted to provide preliminary data on the levels of 13 FOCs in the blood of 48 residents in Catalonia, Spain, in relation to gender and age (25+/-5 and 55+/-5 years). The highest mean concentration was obtained for perfluorooctane sulfonate (PFOS, 7.64 ng/ml), followed by perfluorohexane sulfonate (PFHxS, 3.56 ng/ml) and perfluorooctanoic acid (PFOA, 1.80 ng/ml). Four other FOCs showed mean levels between 0.30 and 0.44 ng/ml, whereas those of the remaining 6 compounds were below the detection limit. Regarding gender, the blood levels of PFHxS and PFOA were significantly higher (p<0.05) in men than in women, while differences according to age were only noted for PFHxS (p<0.05) and perfluorooctane sulfonamide (PFOSA) (p<0.001), for which the levels were higher in the younger (25+/-5 years) group of subjects. A significant correlation between PFOS levels and those of the remaining detected FOCs (except PFDA) was found. In general terms, the current FOC concentrations were lower than those found in recent studies concerning levels of these chemicals in human blood and serum of subjects from different countries.

Background: Only limited data exist on lactation as an exposure source of persistent perfluorinated chemicals (PFCs) for children., Objectives: We studied occurrence and levels of PFCs in human milk in relation to maternal serum together with the temporal trend in milk levels between 1996 and 2004 in Sweden. Matched, individual human milk and serum samples from 12 primiparous women in Sweden were analyzed together with composite milk samples (25-90 women/year) from 1996 to 2004., Results: Eight PFCs were detected in the serum samples, and five of them were also above the detection limits in the milk samples. Perfluorooctanesulfonate (PFOS) and perfluorohexanesulfonate (PFHxS) were detected in all milk samples at mean concentrations of 0.201 ng/mL and 0.085 ng/mL, respectively. Perfluorooctanesulfonamide (PFOSA), perfluorooctanoic acid (PFOA), and perfluorononanoic acid (PFNA) were detected less frequently., Discussion: The total PFC concentration in maternal serum was 32 ng/mL, and the corresponding milk concentration was 0.34 ng/mL. The PFOS milk level was on average 1% of the corresponding serum level. There was a strong association between increasing serum concentration and increasing milk concentration for PFOS (r(2) = 0.7) and PFHxS (r(2) = 0.8). PFOS and PFHxS levels in composite milk samples were relatively unchanged between 1996 and 2004, with a total variation of 20 and 32% coefficient of variation, respectively., Conclusion: The calculated total amount of PFCs transferred by lactation to a breast-fed infant in this study was approximately 200 ng/day. Lactation is a considerable source of exposure for infants, and reference concentrations for hazard assessments are needed.

Objective: Data from the Swedish National Register in Cardiac Care have shown over the last 10 years an enduring gap between optimal treatment of acute myocardial infarction (AMI) according to current guidelines and the treatment actually given. We performed a controlled, prospective study in order to evaluate the effects of applying a multidisciplinary team-based improvement methodology to the use of evidence-based treatments in AMI, together with the use of a modified National Quality Register. The project engaged 25% of the Swedish hospitals., Method: Multidisciplinary teams from 20 hospitals participating in the National Register in Cardiac Care, ranging from small to large hospitals, were trained in continuous quality improvement methodology. Twenty matched hospitals served as controls. Our efforts were focused on finding and applying tools and methods to increase adherence to the national guidelines for 5 different treatments for AMI. For measurement, specially designed quality control charts were made available in the National Register for Cardiac Care., Results: To close the gap, an important issue for the teams was to get all 5 treatments in place. Ten of the hospitals in the study group reduced the gap in 5 of 5 treatments by 50%, while none of the control hospitals did so., Conclusions: This first, controlled prospective study of a registry supported by multidisciplinary team-based improvement methodology showed that this approach led to rapidly improved adherence to AMI guidelines in a broad spectrum of hospitals and that National Quality Registers can be helpful tools.

Background: The adherence to evidence-based treatment guidelines for acute myocardial infarction (AMI) is still suboptimal. Therefore, we designed a study to evaluate the effects of a collaborative quality improvement (QI) intervention on the adherence to AMI guidelines. The intervention used a national web-based quality registry to generate local and regular real-time performance feedback., Methods: A 12-month baseline measurement of the adherence rates was retrospectively collected, comprising the period July 1, 2001, through June 30, 2002. During the intervention period of November 1, 2002, through April 30, 2003, multidisciplinary teams from 19 nonrandomized intervention hospitals were subjected to a multifaceted QI-oriented intervention. Another 19 hospitals, unaware of their status as controls, were matched to the intervention hospitals. During the postintervention measurement period of May 1, 2003, through April 30, 2004, a total of 6726 consecutive patients were included at the intervention (n = 3786) and control (n = 2940) hospitals. The outcome measures comprised 5 Swedish national guideline-derived quality indicators, compared between baseline and postintervention levels in the control and QUICC intervention hospitals., Results: In the control and QI intervention hospitals, the mean absolute increase of patients receiving angiotensin-converting enzyme inhibitors was 1.4% vs 12.6% (P = .002), lipid-lowering therapy 2.3% vs 7.2% (P = .065), clopidogrel 26.3% vs 41.2% (P = .010), heparin/low-molecular weight heparin 5.3% vs 16.3% (P = .010), and coronary angiography 6.2% vs 16.8% (P = .027), respectively. The number of QI intervention hospitals reaching a treatment level of at least 70% in 4 or 5 of the 5 indicators was 15 and 5, respectively. In the control group, no hospital reached 70% or more in just 4 of the 5 indicators., Conclusions: By combining a systematic and multidisciplinary QI collaborative with a web-based national quality registry with functionality allowing real-time performance feedback, major improvements in the adherence to national AMI guidelines can be achieved.

Purpose: To determine persistent organic pollutants in adipose tissue in a patient with kidney cancer., Methods: Adipose tissue was sampled from the abdominal wall during autopsy of a 75-year old man who had died from a kidney cancer. The concentrations of polychlorinated biphenyls (PCBs), p,p'-dichlorodiphenyltrichloroethane (DDE), hexachlorobenzene (HCB), chlordanes and tetrabromodiphenyl ether (TeBDE) were determined on lipid basis. For comparison results from 29 male population based subjects aged 70-80 years were used., Results: All concentrations except for TeBDE were very high in the patient; sum of PCBs 18 808 ng/g fat (median for controls 997), DDE 14 183 (median for controls 751), HCB 424 (median for controls 46), and sum of chlordanes 2 389 (median for controls 62). The patient lost weight from 80 kg to 48 kg when he died, which may have contributed wholly or partly to the very high concentrations of organochlorines., Conclusion: Changes in weight must be recorded in cancer patients and the concentrations of persistent organic pollutants should be normalized to weight. The concentrations in this patient were 10- to almost 40-times higher than in the controls. Such very high concentrations may give clinical symptoms in the final stage of a wasting cancer patient.

A substantial formation of PBDF congeners was observed during photolytic decomposition of decaBDE in toluene. The decaBDE degradation was monitored by chemical and toxicological analysis and in all, twenty-seven mono- to hexasubstituted polybrominated dibenzofurans (PBDFs) were detected in toluene solutions of decabromodiphenyl ether (decaBDE) after irradiation with UV-A, UV-AB and UV-ABC. The concentration levels of PBDFs formed after 16 h of UV exposure increased with wider spectra and were determined to be 3.5, 4.2 and 14 microg/ml after UV-A, UV-AB and UV-ABC irradiation, respectively. In accordance, bioassay derived TEQs (bio-TEQs), determined with the DR-CALUX assay, increased with a similar pattern. The PBDFs formed after the three UV exposures accounted for 0.31%, 0.35% and 1.2% of the initial amount of decaBDE (molar basis). The PBDF congener patterns were consistent in all three UV experiments which imply that no alterations were induced in the PBDF formation or degradation processes due to differences in UV irradiation. However, these processes tended to increase with wider spectra and increasing radiation energy most likely due to the strong absorbance of for example decaBDE at shorter wavelengths. After total decaBDE decomposition the PBDF formation increased significantly in the UV-ABC experiment. The tetra to hexasubstituted BDFs constituted the majority of detected compounds in all experiments. In all samples, the estimated chemical TEQ indicate that the bio-TEQs observed are largely explained by the presence of non-2,3,7,8-substituted PBDFs with relatively low toxicological potencies.

In order to evaluate blood levels of some perfluorinated chemicals (PFCs) and compare them to current levels of classical persistent organic pollutants (POPs) whole blood samples from Sweden were analyzed with respect to 12 PFCs, 37 polychlorinated biphenyls (PCBs), p,p'-dichlorodiphenyl-dichloroethylene (DDE), hexachlorobenzene (HCB), six chlordanes and three polybrominated diphenyl ethers (PBDEs). The median concentration, on whole blood basis, of the sum of PFCs was 20-50 times higher compared to the sum of PCBs and p,p'-DDE, 300-450 times higher than HCB, sum of chlordanes and sum of PBDEs. Estimations of the total body amount of PFCs and lipophilic POPs point at similar body burdens. While levels of for example PCBs and PBDEs are normalized to the lipid content of blood, there is no such general procedure for PFCs in blood. The distributions of a number of perfluorinated compounds between whole blood and plasma were therefore studied. Plasma concentrations were higher than whole blood concentrations for four perfluoroalkylated acids with plasma/whole blood ratios between 1.1 and 1.4, whereas the ratio for perflurooctanesulfonamide (PFOSA) was considerably lower (0.2). This suggests that the comparison of levels of PFCs determined in plasma with levels determined in whole blood should be made with caution. We also conclude that Swedish residents are exposed to a large number of PFCs to the same extent as in USA, Japan, Colombia and the few other countries from which data is available today.

Objective: We sought to study the concentrations of certain persistent organic pollutants with endocrine-disrupting properties in cases with prostate cancer and controls with benign prostate hyperplasia., Methods: Adipose tissue was obtained from 58 cases and 20 controls., Results: The median concentration among controls was used as cut-off in the statistical analysis. In the total material, a greater-than median concentration of PCB congener 153 yielded an odds ratio (OR) of 3.15 and 95% confidence interval (CI) of 1.04-9.54 and one chlordane type, trans-chlordane, yielded OR 3.49 (95% CI = 1.08-11.2). In the group of case subjects with PSA levels greater than the median level of 16.5 ng/mL, PCB 153 was OR 30.3 (95% CI = 3.24-284), hexachlorobenzene OR = 9.84 (95% CI = 1.99-48.5), trans-chlordane OR = 11.0 (95% CI = 1.87-64.9), and the chlordane-type MC6 OR = 7.58 (95% CI = 1.65-34.9). The grouping of PCBs according to structural and biological activity was found to produce significantly increased risks for enzyme and phenobarbital-inducing PCBs and lower chlorinated PCBs in the case group with PSA levels greater than 16.5 ng/mL., Conclusions: These chemicals might be of etiologic significance but need to be further investigated. The biological relevance of the arbitrary cut-off point of PSA is unclear.

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.

A gas chromatography-high-resolution mass spectrometry (GC-HRMS) method using solid-phase microextraction (SPME) for the determination of 2,4,6-trichloroanisole (TCA) and 2,4,6-tribromoanisole (TBA) in wine at low ng L(-1) levels was developed. A robust SPME method was developed by optimizing several different parameters, including type of fiber, salt addition, sample volume, extraction and desorption time. The quantification limit for TCA and TBA in wine was lowered substantially using GC-HRMS in combination with the optimized SPME method and allowed the detection of low analyte concentrations (ng L(-1)) with good accuracy. Limits of quantification for red wine of 0.3 ng L(-1) for TCA and 0.2 ng L(-1) for TBA with gas chromatography-negative chemical ionization mass spectrometry and 0.03 ng L(-1) for TCA and TBA were achieved using GC-HRMS. The method was applied to 30 wines of which 4 wines were sensorically qualified as cork defected. TCA was found in three of these wines with concentrations in the range 2-25 ng L(-1). TBA was not detected in any of the samples.

Testicular cancer is the most common tumour type in young men. In Sweden the annual age-adjusted incidence increased significantly by 2.4% during the time period 1984-1993 and during 1994-2003 by 1.4%. Exposure to endocrine disrupting chemicals during the foetal period has been postulated to be a risk factor. In this investigation we studied the concentrations of chlorinated biphenyls (PCBs), p,p'-dichlorodiphenyl-dichloroethylene (pp'-DDE), hexachlorobenzene (HCB), chlordanes and polybrominated diphenylethers (PBDEs) in 58 cases with testicular cancer and 61 age-matched controls. Furthermore, case and control mothers were also asked to participate and 44 case mothers and 45 control mothers agreed. No significant differences were found between cases and controls. Case mothers had in general higher concentrations of these chemicals. For the sum of PCBs an odds ratio (OR) = 3.8, 95% confidence interval (CI) = 1.4-10 was calculated using the median concentration for the controls as cut-off value. For HCB OR = 4.4, CI = 1.7-12 and for PBDE OR = 2.5, 95% CI = 1.02-6.0 were obtained, whereas OR was not significantly increased for pp'-DDE and sum of chlordanes. The cases were born during a period with high concentrations of persistent organic pollutants (POPs) in humans. The decline of the increasing incidence of testicular cancer during recent years may reflect decreasing body burden of certain POPs since the 1980s.

The HBV-NP model is a newly developed water quality model that describes the turnover and fluxes of both nitrogen and phosphorous. It is based on the conceptual precipitation/runoff HBV model. The HBV-NP model was applied for simulation of nitrogen for the Rönneå catchment in southern Sweden. The catchment was divided into 64 subcatchments in the model. Discharge measurements from six stations and nitrogen measurements from 12 stations were used in the calibration of parameters in the model. Eight automatic calibrations were performed with different combinations of time periods, objective functions, and levels of the nitrogen load in the model. A regionally extended interpretation of the Nash-Sutcliffe R2 criterion was used in the calibration. In the evaluation of the criterion, the errors were summed over both time steps and sampling points. Scenario simulations of combined measures for reduction of nitrogen load into the sea by 30% were thereafter performed with the eight sets of parameters established by calibration. The model parameters were not uniquely defined by the calibration. However, the simulated relative reduction of nitrogen load into the sea was relatively insensitive to the choice of parameter set, given the available input sources, variables, and data.

A method for the determination of perfluorooctanesulfonate (PFOS) and perfluorooctanoic acid (PFOA) simultaneously with 10 closely related perfluorochemicals (PFCs) in human whole blood was developed and validated. PFOS and PFOA are used in various applications, for example, as surfactants and plastic additives, and are subject to environmental and health research due to their persistence. The main part of the data on PFCs in human blood is from serum samples, analyzed mainly by ion pair extraction followed by high-performance liquid chromatography (HPLC) and negative electrospray (ESI) tandem mass spectrometry (MS/MS). The analytical method developed here is suitable for human whole blood and involves solid-phase extraction (SPE) and HPLC negative electrospray single quadrupole mass spectrometry (HPLC/ES-MS). A whole blood aliquot was treated with formic acid and extracted on a octadecyl (C18) SPE column. The PFCs were isolated with methanol, and quantification was performed using single quadrupole mass spectrometry and perfluoroheptanoic acid as internal standard. Validation was performed in the range 0.3-194 ng/mL with recovery between 64 and 112% and limit of detection in the 0.1-0.5 ng/mL range for 11 of the 12 PFCs studied. We applied this method to 20 whole blood samples collected in 1997-2000 from the Swedish population in the ages 24-72. Eleven of the 12 PFCs were detected, and they were quantitatively and qualitatively confirmed using triple quadrupole LC/MS/MS analysis. PFOS, perfluorooctanesulfonamide, perfluorohexanesulfonate, PFOA and perfluorononanoic acid were quantified in all samples. In addition, perfluorohexanoic acid, perfluorodecanoic acid, perfluorodecanesulfonate, perfluoroundecanoic acid, perfluorododecanoic acid, and perfluorotetradecanoic acid were detected in some samples. This study shows that SPE and single quadrupole MS can be applied for extraction and quantification of PFCs in human whole blood, resulting in selectivity and low detection limits.

Objective: To evaluate in a case-control study possible risk of endometrial cancer associated with environmental endocrine disruptors., Methods: We analyzed the adipose tissue concentrations of polychlorinated biphenyls, hexachlorobenzene (HCB), p,p'-dichlorodiphenyl-dichloroethylene (p,p'-DDE), chlordanes, and polybrominated biphenyls in 76 cases with endometrial cancer and 39 controls with benign endometrial hyperplasia., Results: For the different chemicals, odds ratios (ORs) and 95% confidence intervals (CI) were close to unity taking the median concentration among the controls as cutoff value. However, for p,p'-DDE OR = 1.9, 95% CI = 0.8-4.8 was obtained. Additional estrogen replacement therapy yielded in this category OR = 2.3, 95% CI = 0.6-8.6., Conclusion: The results suggest an interaction between p,p'-DDE and estrogen replacement drugs in the etiology of endometrial cancer, although no significant associations were found.

To assess the influence of a new hazardous waste incinerator (HWI) on public health, a preoperational monitoring program was established during the period of construction. In this study, the levels of polychlorinated dibenzo-p-dioxins (PCDD) and dibenzofurans (PCDF) accumulated in adipose tissue of 15 autopsied subjects living in the area under potential impact of the HWI were determined after approximately 3 years of regular operations in the facility. The non-ortho PCBs 77, 126 and 169 were also determined. PCDD/F concentrations ranged between 1.5 and 41 pg WHO-TEQ/g fat (2.4 and 72 WHO-TEQ/g fat, respectively, including PCBs), with a mean value of 11 pg WHO-TEQ/g fat and a median value of 7.4 pg WHO-TEQ/g fat (22 and 13 WHO-TEQ/g fat, respectively, including PCBs). In the baseline study, the mean level of PCDD/Fs was 36 pg WHO-TEQ/g fat (61 pg WHO-TEQ/g fat, including non-ortho PCBs 77, 126 and 169), which means a reduction of 70% (64% including PCBs). This notable reduction is in accordance with the important decrease observed in recent years in PCDD/F intake through the diet. The current concentrations of PCDD/Fs in human adipose tissue, as well as recent data on PCDD/F levels in plasma and breast milk of subjects living in the vicinity of the same HWI, indicate that there is not any additional significant exposure to PCDD/Fs for this population.

An increasing incidence of testicular cancer has been reported from several western countries during the last decades. According to current hypothesis testicular cancer is initiated during the foetal period and exposure to endocrine disruptors such as some persistent organic pollutants has been of concern. We have previously reported the results for concentrations of polychlorinated biphenyls (PCBs), p,p'-dichlorodiphenyl-dichloroethylene (pp'-DDE), hexachlorobenzene (HCB) and chlordanes in 58 cases with testicular cancer, 61 age-matched controls and 44 case mothers and 45 control mothers. In that report, significant increase of odds ratio (OR) was found for sum of PCBs, HCB, trans- and cis-nonachlordane in case mothers. These data have now been further analysed for 37 congeners of PCBs. No significant differences were found among cases and controls. However, case mothers had significantly increased concentrations of a number of PCB congeners. A priori decided grouping of PCBs yielded for oestrogenic PCBs OR = 2.4, 95% confidence interval (CI) = 0.95-6.0, enzyme-inducing PCBsOR = 2.6, 95% CI = 1.03-6.5 and toxic equivalents (TEQ) yielded OR = 3.3, 95% CI = 1.3-8.4. These data further elucidate the role of foetal exposure to different PCB congeners in the aetiology of testicular cancer.