| 1. |
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| 2. |
- Vogel, Jacob W., et al.
(författare)
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Four distinct trajectories of tau deposition identified in Alzheimer’s disease
- 2021
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Ingår i: Nature Medicine. - : Springer Science and Business Media LLC. - 1078-8956 .- 1546-170X. ; 27:5, s. 871-881
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Tidskriftsartikel (refereegranskat)abstract
- Alzheimer’s disease (AD) is characterized by the spread of tau pathology throughout the cerebral cortex. This spreading pattern was thought to be fairly consistent across individuals, although recent work has demonstrated substantial variability in the population with AD. Using tau-positron emission tomography scans from 1,612 individuals, we identified 4 distinct spatiotemporal trajectories of tau pathology, ranging in prevalence from 18 to 33%. We replicated previously described limbic-predominant and medial temporal lobe-sparing patterns, while also discovering posterior and lateral temporal patterns resembling atypical clinical variants of AD. These ‘subtypes’ were stable during longitudinal follow-up and were replicated in a separate sample using a different radiotracer. The subtypes presented with distinct demographic and cognitive profiles and differing longitudinal outcomes. Additionally, network diffusion models implied that pathology originates and spreads through distinct corticolimbic networks in the different subtypes. Together, our results suggest that variation in tau pathology is common and systematic, perhaps warranting a re-examination of the notion of ‘typical AD’ and a revisiting of tau pathological staging. © 2021, The Author(s), under exclusive licence to Springer Nature America, Inc.
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| 3. |
- Zhou, XP, et al.
(författare)
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Non-coding variability at the APOE locus contributes to the Alzheimer's risk
- 2019
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 3310-
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Tidskriftsartikel (refereegranskat)abstract
- Alzheimer’s disease (AD) is a leading cause of mortality in the elderly. While the coding change of APOE-ε4 is a key risk factor for late-onset AD and has been believed to be the only risk factor in the APOE locus, it does not fully explain the risk effect conferred by the locus. Here, we report the identification of AD causal variants in PVRL2 and APOC1 regions in proximity to APOE and define common risk haplotypes independent of APOE-ε4 coding change. These risk haplotypes are associated with changes of AD-related endophenotypes including cognitive performance, and altered expression of APOE and its nearby genes in the human brain and blood. High-throughput genome-wide chromosome conformation capture analysis further supports the roles of these risk haplotypes in modulating chromatin states and gene expression in the brain. Our findings provide compelling evidence for additional risk factors in the APOE locus that contribute to AD pathogenesis.
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| 4. |
- Stephen, D, et al.
(författare)
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Continental-scale patterns of nutrient and fish effects on shallow lakes: introduction to a pan-European mesocosm experiment
- 2004
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Ingår i: Freshwater Biology. - : Wiley. - 0046-5070 .- 1365-2427. ; 49:12, s. 1517-1524
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Tidskriftsartikel (refereegranskat)abstract
- 1. Shallow lake ecosystems are normally dominated by submerged and emergent plants. Biological stabilising mechanisms help preserve this dominance. The systems may switch to dominance by phytoplankton, however, with loss of submerged plants. This process usually takes place against a background of increasing nutrient loadings but also requires additional switch mechanisms, which damage the plants or interfere with their stabilising mechanisms. 2. The extent to which the details or even major features of this general model may change with geographical location are not clear. Manipulation of the fish community (biomanipulation) has often been used to clear the water of algae and restore the aquatic plants in northerly locations, but it is again not clear whether this is equally appropriate at lower latitudes. 3. Eleven parallel experiments (collectively the International Mesocosm Experiment, IME) were carried out in six lakes in Finland, Sweden, England, the Netherlands and Spain in 1998 and 1999 to investigate the between-year and large-scale spatial variation in relationships between nutrient loading and zooplanktivorous fish on submerged plant and plankton communities in shallow lakes. 4. Comparability of experiments in different locations was achieved to a high degree. Cross-laboratory comparisons of chemical analyses revealed some systematic differences between laboratories. These are unlikely to lead to major misinterpretations. 5. Nutrient addition, overall, had its greatest effect on water chemistry then substantial effects on phytoplankton and zooplankton. Fish addition had its major effect on zooplankton and did not systematically change the water chemistry. There was no trend in the relative importance of fish effects with latitude, but nutrient addition affected more variables with decreasing latitude. 6. The relative importance of top-down and bottom-up influences on the plankton differed in different locations and between years at the same location. The outcome of the experiments in different years was more predictable with decreasing latitude and this was attributed to more variable weather at higher latitudes that created more variable starting conditions for the experiments.
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| 5. |
- Moss, B, et al.
(författare)
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Continental-scale patterns of nutrient and fish effects on shallow lakes: synthesis of a pan-European mesocosm experiment
- 2004
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Ingår i: Freshwater Biology. - : Wiley. - 0046-5070 .- 1365-2427. ; 49:12, s. 1633-1649
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Tidskriftsartikel (refereegranskat)abstract
- 1. Results are analysed from 11 experiments in which effects of fish addition and nutrient loading on shallow lakes were studied in mesocosms. The experiments, five in 1998, six in 1999, were carried out in six lakes, distributed from Finland to southern Spain, according to a standard protocol. 2. Effects of the treatments on 29 standard chemical, phytoplankton and zooplankton variables are examined to assess the relative importance of bottom-up (nutrient enrichment) and top-down (fish predation) effects. For each year, the experiments in different locations are treated as replicates in a meta-analysis. Results of individual experiments are then compared in terms of the patterns of significant influences of nutrient addition and fish predation with these overall results (the baseline), and between years in the same location. 3. The overall meta-analysis gave consistent results across the 2 years, with nutrient loading influencing all of the chemical variables, and on average 31% of primary producer and 39% of zooplankton variables. In contrast, fish influenced none of the chemical variables, 11% of the primary producer and 44% of the zooplankton variables. Nutrient effects on the system were thus about three times greater than fish effects, although fish effects were not inconsiderable. 4. The relative importance of nutrients and fish in individual experiments often differed between years at the same location and effects deviated to varying degrees from the baseline. These deviations were treated as measures of consistency (predictability) of conclusions in repeat experiments. Consistency increased southwards and this is interpreted as a consequence of more variable annual weather northwards. 5. The influence of nutrient loading was greater southwards and this was probably manifested through naturally greater annual macrophyte abundance in warmer locations in consequence of the longer plant growing-season. There was no trend in the relative importance of fish effects with latitude but this may partly be an artefact of the simple fish community used. These findings suggest that nutrient control should be a greater priority than biomanipulation in the restoration of eutrophicated shallow lakes in warm temperate regions. 6. Starting conditions affected the outcome of experiments. High initial concentrations of total phosphorus and planktonic chlorophyll a concentration (created by local conditions prior to the experiment) led to de-emphasis of the importance of nutrient loading in the experiment.
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| 6. |
- Van de Bund, WJ, et al.
(författare)
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Responses of phytoplankton to fish predation and nutrient loading in shallow lakes: a pan-European mesocosm experiment
- 2004
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Ingår i: Freshwater Biology. - : Wiley. - 0046-5070 .- 1365-2427. ; 49:12, s. 1608-1618
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Tidskriftsartikel (refereegranskat)abstract
- 1. The impacts of nutrients (phosphorus and nitrogen) and planktivorous fish on phytoplankton composition and biomass were studied in six shallow, macrophyte-dominated lakes across Europe using mesocosm experiments. 2. Phytoplankton biomass was more influenced by nutrients than by densities of planktivorous fish. Nutrient addition resulted in increased algal biomass at all locations. In some experiments, a decrease was noted at the highest nutrient loadings, corresponding to added concentrations of 1 mg L-1 P and 10 mg L-1 N. 3. Chlorophyll a was a more precise parameter to quantify phytoplankton biomass than algal biovolume, with lower within-treatment variability. 4. Higher densities of planktivorous fish shifted phytoplankton composition toward smaller algae (GALD < 50 mum). High nutrient loadings selected in favour of chlorophytes and cyanobacteria, while biovolumes of diatoms and dinophytes decreased. High temperatures also may increase the contribution of cyanobacteria to total phytoplankton biovolume in shallow lakes.
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| 7. |
- Calle Cordón, Álvaro, et al.
(författare)
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Combined RAMS and LCC analysis in railway and road transport infrastructures
- 2018
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Ingår i: Proceedings of 7th Transport Research Arena TRA. - Vienna, Austria.
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Konferensbidrag (refereegranskat)abstract
- Life-cycle cost (LCC) analysis is an assessment technique used to evaluate costs incurred during the life-cycle of a system to help in long term decision making. In railway and road transport infrastructures, costs are subject to numerous uncertainties associated to the operation and maintenance phase. By integrating in the LCC the stochastic nature of failure using Reliability, Maintainability, Availability and Safety (RAMS) analyses, maintenance costs can be more reliably estimated. This paper presents an innovative approach for a combined RAMS&LCC methodology for linear transport infrastructures which has been developed under the H2020 project INFRALERT. Results of the application of such methodology in two real use cases are shown, one for rail and another one for road. The use cases show how the approach is implemented in practice.
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| 8. |
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| 9. |
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| 10. |
- Didion, JP, et al.
(författare)
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R2d2 Drives Selfish Sweeps in the House Mouse
- 2016
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Ingår i: Molecular biology and evolution. - : Oxford University Press (OUP). - 1537-1719 .- 0737-4038. ; 33:6, s. 1381-1395
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Tidskriftsartikel (refereegranskat)
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| 11. |
- Calle-Cordón, Álvaro, et al.
(författare)
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Integration of RAMS in LCC analysis for linear transportinfrastructures : A case study for railways
- 2017
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Ingår i: IOP Conference Series. - : Institute of Physics (IOP). - 1757-8981 .- 1757-899X. ; 236
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Tidskriftsartikel (refereegranskat)abstract
- Life-cycle cost (LCC) analysis is an economic technique used to assess the totalcosts associated with the lifetime of a system in order to support decision making in long termstrategic planning. For complex systems, such as railway and road infrastructures, the cost ofmaintenance plays an important role in the LCC analysis. Costs associated with maintenanceinterventions can be more reliably estimated by integrating the probabilistic nature of thefailures associated to these interventions in the LCC models. Reliability, Maintainability,Availability and Safety (RAMS) parameters describe the maintenance needs of an asset in aquantitative way by using probabilistic information extracted from registered maintenanceactivities. Therefore, the integration of RAMS in the LCC analysis allows obtaining reliablepredictions of system maintenance costs and the dependencies of these costs with specific costdrivers through sensitivity analyses. This paper presents an innovative approach for acombined RAMS & LCC methodology for railway and road transport infrastructures beingdeveloped under the on-going H2020 project INFRALERT. Such RAMS & LCC analysisprovides relevant probabilistic information to be used for condition and risk-based planning ofmaintenance activities as well as for decision support in long term strategic investmentplanning.
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| 12. |
- Ferrando, Carlos, et al.
(författare)
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Effects of oxygen on post-surgical infections during an individualised perioperative open-lung ventilatory strategy : a randomised controlled trial
- 2020
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Ingår i: British Journal of Anaesthesia. - : ELSEVIER SCI LTD. - 0007-0912 .- 1471-6771. ; 124:1, s. 110-120
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Tidskriftsartikel (refereegranskat)abstract
- Background: We aimed to examine whether using a high fraction of inspired oxygen (FIO2) in the context of an individualised intra- and postoperative open-lung ventilation approach could decrease surgical site infection (SSI) in patients scheduled for abdominal surgery. Methods: We performed a multicentre, randomised controlled clinical trial in a network of 21 university hospitals from June 6, 2017 to July 19, 2018. Patients undergoing abdominal surgery were randomly assigned to receive a high (0.80) or conventional (0.3) FIO2 during the intraoperative period and during the first 3 postoperative hours. All patients were mechanically ventilated with an open-lung strategy, which included recruitment manoeuvres and individualised positive end-expiratory pressure for the best respiratory-system compliance, and individualised continuous postoperative airway pressure for adequate peripheral oxyhaemoglobin saturation. The primary outcome was the prevalence of SSI within the first 7 postoperative days. The secondary outcomes were composites of systemic complications, length of intensive care and hospital stay, and 6-month mortality. Results: We enrolled 740 subjects: 371 in the high FIO2 group and 369 in the low FIO2 group. Data from 717 subjects were available for final analysis. The rate of SSI during the first postoperative week did not differ between high (8.9%) and low (9.4%) FIO2 groups (relative risk [RR]: 0.94; 95% confidence interval [CI]: 0.59-1.50; P=0.90]). Secondary outcomes, such as atelectasis (7.7% vs 9.8%; RR: 0.77; 95% CI: 0.48-1.25; P=0.38) and myocardial ischaemia (0.6% [n=2] vs 0% [n=0]; P=0.47) did not differ between groups. Conclusions: An oxygenation strategy using high FIO2 compared with conventional FIO2 did not reduce postoperative SSIs in abdominal surgery. No differences in secondary outcomes or adverse events were found.
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| 13. |
- Garnaud, C., et al.
(författare)
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Toxoplasma gondii-specific IgG avidity testing in pregnant women
- 2020
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Ingår i: Clinical Microbiology and Infection. - : Elsevier. - 1198-743X .- 1469-0691. ; 26:9, s. 1155-1160
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Forskningsöversikt (refereegranskat)abstract
- Background: The parasite Toxoplasma gondii can cause congenital toxoplasmosis following primary infection in a pregnant woman. It is therefore important to distinguish between recent and past infection when both T. gondii-specific IgM and IgG are detected in a single serum in pregnant women. Toxoplasma gondii-specific IgG avidity testing is an essential tool to help to date the infection. However, interpretation of its results can be complex.Objectives: To review the benefits and limitations of T. gondii-specific avidity testing in pregnant women, to help practitioners to interpret the results and adapt the patient management.Sources: PubMed search with the keywords avidity, toxoplasmosis and Toxoplasma gondii for articles published from 1989 to 2019.Content: Toxoplasma gondii-specific IgG avidity testing remains a key tool for dating a T. gondii infection in immunocompetent pregnant women. Several commercial assays are available and display comparable performances. A high avidity result obtained on a first-trimester serum sample is indicative of a past infection, which occurred before pregnancy. To date, a low avidity result must still be considered as non-informative to date the infection, although some authors suggest that very low avidity results are highly suggestive of recent infections depending on the assay. Interpretation of low or grey zone avidity results on a first-trimester serum sample, as well as any avidity result on a second-trimester or third-trimester serum sample, is more complex and requires recourse to expert toxoplasmosis laboratories. Implications: Although used for about 30 years, T. gondii-specific avidity testing has scarcely evolved. The same difficulties in interpretation have persisted over the years. Some authors have proposed additional thresholds to exclude an infection of <9 months, or in contrast to confirm a recent infection. Such thresholds would be of great interest to adapt management of pregnant women and avoid unnecessary treatment; however, they need confirmation and further studies.
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| 14. |
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| 15. |
- Lazaridis, Iosif, et al.
(författare)
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Ancient human genomes suggest three ancestral populations for present-day Europeans
- 2014
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 513:7518, s. 409-
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Tidskriftsartikel (refereegranskat)abstract
- We sequenced the genomes of a similar to 7,000-year-old farmer from Germany and eight similar to 8,000-year-old hunter-gatherers from Luxembourg and Sweden. We analysed these and other ancient genomes(1-4) with 2,345 contemporary humans to show that most present-day Europeans derive from at least three highly differentiated populations: west European hunter-gatherers, who contributed ancestry to all Europeans but not to Near Easterners; ancient north Eurasians related to Upper Palaeolithic Siberians(3), who contributed to both Europeans and Near Easterners; and early European farmers, who were mainly of Near Eastern origin but also harboured west European hunter-gatherer related ancestry. We model these populations' deep relationships and show that early European farmers had similar to 44% ancestry from a 'basal Eurasian' population that split before the diversification of other non-African lineages.
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| 17. |
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