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| 2. |
- Aamodt, K., et al.
(författare)
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The ALICE experiment at the CERN LHC
- 2008
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Ingår i: Journal of Instrumentation. - 1748-0221. ; 3:S08002
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Forskningsöversikt (refereegranskat)abstract
- ALICE (A Large Ion Collider Experiment) is a general-purpose, heavy-ion detector at the CERN LHC which focuses on QCD, the strong-interaction sector of the Standard Model. It is designed to address the physics of strongly interacting matter and the quark-gluon plasma at extreme values of energy density and temperature in nucleus-nucleus collisions. Besides running with Pb ions, the physics programme includes collisions with lighter ions, lower energy running and dedicated proton-nucleus runs. ALICE will also take data with proton beams at the top LHC energy to collect reference data for the heavy-ion programme and to address several QCD topics for which ALICE is complementary to the other LHC detectors. The ALICE detector has been built by a collaboration including currently over 1000 physicists and engineers from 105 Institutes in 30 countries, Its overall dimensions are 16 x 16 x 26 m(3) with a total weight of approximately 10 000 t. The experiment consists of 18 different detector systems each with its own specific technology choice and design constraints, driven both by the physics requirements and the experimental conditions expected at LHC. The most stringent design constraint is to cope with the extreme particle multiplicity anticipated in central Pb-Pb collisions. The different subsystems were optimized to provide high-momentum resolution as well as excellent Particle Identification (PID) over a broad range in momentum, up to the highest multiplicities predicted for LHC. This will allow for comprehensive studies of hadrons, electrons, muons, and photons produced in the collision of heavy nuclei. Most detector systems are scheduled to be installed and ready for data taking by mid-2008 when the LHC is scheduled to start operation, with the exception of parts of the Photon Spectrometer (PHOS), Transition Radiation Detector (TRD) and Electro Magnetic Calorimeter (EMCal). These detectors will be completed for the high-luminosity ion run expected in 2010. This paper describes in detail the detector components as installed for the first data taking in the summer of 2008.
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| 3. |
- Bouyoucef, S E, et al.
(författare)
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Poster Session 2 : Monday 4 May 2015, 08
- 2015
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Ingår i: European Heart Journal Cardiovascular Imaging. - : Oxford University Press (OUP). - 2047-2404 .- 2047-2412. ; 16 Suppl 1
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Tidskriftsartikel (refereegranskat)
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| 4. |
- Menden, MP, et al.
(författare)
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Community assessment to advance computational prediction of cancer drug combinations in a pharmacogenomic screen
- 2019
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 2674-
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Tidskriftsartikel (refereegranskat)abstract
- The effectiveness of most cancer targeted therapies is short-lived. Tumors often develop resistance that might be overcome with drug combinations. However, the number of possible combinations is vast, necessitating data-driven approaches to find optimal patient-specific treatments. Here we report AstraZeneca’s large drug combination dataset, consisting of 11,576 experiments from 910 combinations across 85 molecularly characterized cancer cell lines, and results of a DREAM Challenge to evaluate computational strategies for predicting synergistic drug pairs and biomarkers. 160 teams participated to provide a comprehensive methodological development and benchmarking. Winning methods incorporate prior knowledge of drug-target interactions. Synergy is predicted with an accuracy matching biological replicates for >60% of combinations. However, 20% of drug combinations are poorly predicted by all methods. Genomic rationale for synergy predictions are identified, including ADAM17 inhibitor antagonism when combined with PIK3CB/D inhibition contrasting to synergy when combined with other PI3K-pathway inhibitors in PIK3CA mutant cells.
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| 5. |
- Neumann, J. T., et al.
(författare)
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Application of High-Sensitivity Troponin in Suspected Myocardial Infarction
- 2019
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Ingår i: New England Journal of Medicine. - : MASSACHUSETTS MEDICAL SOC. - 0028-4793 .- 1533-4406. ; 380:26, s. 2529-2540
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundData regarding high-sensitivity troponin concentrations in patients presenting to the emergency department with symptoms suggestive of myocardial infarction may be useful in determining the probability of myocardial infarction and subsequent 30-day outcomes. MethodsIn 15 international cohorts of patients presenting to the emergency department with symptoms suggestive of myocardial infarction, we determined the concentrations of high-sensitivity troponin I or high-sensitivity troponin T at presentation and after early or late serial sampling. The diagnostic and prognostic performance of multiple high-sensitivity troponin cutoff combinations was assessed with the use of a derivation-validation design. A risk-assessment tool that was based on these data was developed to estimate the risk of index myocardial infarction and of subsequent myocardial infarction or death at 30 days. ResultsAmong 22,651 patients (9604 in the derivation data set and 13,047 in the validation data set), the prevalence of myocardial infarction was 15.3%. Lower high-sensitivity troponin concentrations at presentation and smaller absolute changes during serial sampling were associated with a lower likelihood of myocardial infarction and a lower short-term risk of cardiovascular events. For example, high-sensitivity troponin I concentrations of less than 6 ng per liter and an absolute change of less than 4 ng per liter after 45 to 120 minutes (early serial sampling) resulted in a negative predictive value of 99.5% for myocardial infarction, with an associated 30-day risk of subsequent myocardial infarction or death of 0.2%; a total of 56.5% of the patients would be classified as being at low risk. These findings were confirmed in an external validation data set. ConclusionsA risk-assessment tool, which we developed to integrate the high-sensitivity troponin I or troponin T concentration at emergency department presentation, its dynamic change during serial sampling, and the time between the obtaining of samples, was used to estimate the probability of myocardial infarction on emergency department presentation and 30-day outcomes.
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| 6. |
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| 8. |
- Mason, Robert P., et al.
(författare)
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The Global Marine Selenium Cycle : Insights From Measurements and Modeling
- 2018
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Ingår i: Global Biogeochemical Cycles. - 0886-6236 .- 1944-9224. ; 32:12, s. 1720-1737
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Tidskriftsartikel (refereegranskat)abstract
- Anthropogenic activities have increased the selenium (Se) concentration in the biosphere, but the overall impact on the ocean has not been examined. While Se is an essential nutrient for microorganisms, there is little information on the impact of biological processes on the concentration and speciation of Se in the ocean. Additionally, other factors controlling the distribution and concentration of Se species are poorly understood. Here we present data gathered in the subtropical Pacific Ocean during a cruise in 2011, and we used these field data and the literature, as well as laboratory photochemical experiments examining the stability and degradation of inorganic Se (both Se (IV) and Se (VI)) and dimethyl selenide, to further constrain the cycling of Se in the upper ocean. We also developed a multibox model for the biosphere to examine the impact of anthropogenic emissions on the concentration and distribution of Se in the ocean. The model concurs with the field data indicating that the Se concentration has increased in the upper ocean waters over the past 30 years. Our observational studies and model results suggest that Se (VI) is taken up by phytoplankton in the surface ocean, in contrast to the results of laboratory culture experiments. In conclusion, while anthropogenic inputs have markedly increased Se in the atmosphere (42%) and net deposition to the ocean (38%) and terrestrial landscape (41%), the impact on Se in the ocean is small (3% increase in the upper ocean). This minimal response reflects its long marine residence time. Plain Language Summary We measured selenium in water and particles during a cruise in the Pacific Ocean and use this data along with laboratory photochemcial experiments to examine the formation and degradation of the various Se forms in the upper ocean. We also developed a box model to examine how anthropogenic activities have changed the Se concentration throughout the ocean the potential future impacts and to highlight areas of Se biogeochemistry that need further study.
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| 9. |
- Song, S., et al.
(författare)
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Top-down constraints on atmospheric mercury emissions and implications for global biogeochemical cycling
- 2015
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Ingår i: Atmospheric Chemistry And Physics. - : Copernicus GmbH. - 1680-7316 .- 1680-7324. ; 15:12, s. 7103-7125
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Tidskriftsartikel (refereegranskat)abstract
- We perform global-scale inverse modeling to constrain present-day atmospheric mercury emissions and relevant physiochemical parameters in the GEOS-Chem chemical transport model. We use Bayesian inversion methods combining simulations with GEOS-Chem and ground-based Hg-0 observations from regional monitoring networks and individual sites in recent years. Using optimized emissions/parameters, GEOS-Chem better reproduces these ground-based observations and also matches regional over-water Hg-0 and wet deposition measurements. The optimized global mercury emission to the atmosphere is 5.8 Gg yr(-1). The ocean accounts for 3.2 Gg yr(-1) (55 % of the total), and the terrestrial ecosystem is neither a net source nor a net sink of Hg-0. The optimized Asian anthropogenic emission of Hg-0 (gas elemental mercury) is 650-1770 Mg yr(-1), higher than its bottom-up estimates (550-800 Mg yr(-1)). The ocean parameter inversions suggest that dark oxidation of aqueous elemental mercury is faster, and less mercury is removed from the mixed layer through particle sinking, when compared with current simulations. Parameter changes affect the simulated global ocean mercury budget, particularly mass exchange between the mixed layer and subsurface waters. Based on our inversion results, we re-evaluate the long-term global biogeochemical cycle of mercury, and show that legacy mercury becomes more likely to reside in the terrestrial ecosystem than in the ocean. We estimate that primary anthropogenic mercury contributes up to 23 % of present-day atmospheric deposition.
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| 10. |
- Dastoor, Ashu, et al.
(författare)
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Arctic mercury cycling
- 2022
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Ingår i: Nature Reviews Earth & Environment. - : Springer Nature. - 2662-138X. ; 3:4, s. 270-286
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Forskningsöversikt (refereegranskat)abstract
- Anthropogenic mercury (Hg) emissions have driven marked increases in Arctic Hg levels,which are now being impacted by regional warming, with uncertain ecological consequences. This Review presents a comprehensive assessment of the present-day total Hg mass balance in the Arctic. Over 98% of atmospheric Hg is emitted outside the region and is transported to the Arctic via long-range air and ocean transport. Around two thirds of this Hg is deposited in terrestrial ecosystems, where it predominantly accumulates in soils via vegetation uptake. Rivers and coastal erosion transfer about 80 Mg year−1 of terrestrial Hg to the Arctic Ocean, in approximate balance with modelled net terrestrial Hg deposition in the region. The revised Arctic Ocean Hg mass balance suggests net atmospheric Hg deposition to the ocean and that Hg burial in inner-shelf sediments is underestimated (up to >100%), needing seasonal observations of sediment-oceanHg exchange. Terrestrial Hg mobilization pathways from soils and the cryosphere (permafrost, ice, snow and glaciers) remain uncertain. Improved soil, snowpack and glacial Hg inventories, transfer mechanisms of riverine Hg releases under accelerated glacier and soil thaw, coupled atmosphere– terrestrial modelling and monitoring of Hg in sensitive ecosystems such as fjords can help toanticipate impacts on downstream Arctic ecosystems.
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| 11. |
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| 14. |
- Haque, Faiz, et al.
(författare)
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Per- and polyfluoroalkyl substances (PFAS) in white-tailed sea eagle eggs from Sweden: Temporal trends (1969-2021), spatial variations, fluorine mass balance, and suspect screening
- 2023
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Ingår i: Environmental Science. - 2050-7887 .- 2050-7895.
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Tidskriftsartikel (refereegranskat)abstract
- Temporal and spatial trends of 15 per- and polyfluoroalkyl substances (PFAS) were determined in white-tailed sea eagle (WTSE) eggs (Haliaeetus albicilla) from two inland and two coastal regions of Sweden between 1969 and 2021. PFAS concentrations generally increased from ∼1969 to ∼1990s–2010 (depending on target and site) and thereafter plateaued or declined, with perfluorooctane sulfonamide (FOSA) and perfluorooctane sulfonate (PFOS) declining faster than most perfluoroalkyl carboxylic acids (PFCAs). The net result was a shift in the PFAS profile from PFOS-dominant in 1969–2010 to an increased prevalence of PFCAs over the last decade. Further, during the entire period higher PFAS concentrations were generally observed in coastal populations, possibly due to differences in diet and/or proximity to more densely populated areas. Fluorine mass balance determination in pooled samples from three of the regions (2019–2021) indicated that target PFAS accounted for the vast majority (i.e. 81–100%) of extractable organic fluorine (EOF). Nevertheless, high resolution mass-spectrometry-based suspect screening identified 55 suspects (31 at a confidence level [CL] of 1–3 and 24 at a CL of 4–5), of which 43 were substances not included in the targeted analysis. Semi-quantification of CL ≤ 2 suspects increased the identified EOF to >90% in coastal samples. In addition to showing the impact of PFAS regulation and phase-out initiatives, this study demonstrates that most extractable organofluorine in WTSE eggs is made up of known (legacy) PFAS, albeit with low levels of novel substances.
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| 15. |
- Helbig, K. L., et al.
(författare)
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De Novo Pathogenic Variants in CACNA1E Cause Developmental and Epileptic Encephalopathy with Contractures, Macrocephaly, and Dyskinesias
- 2018
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Ingår i: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297 .- 1537-6605. ; 103:5, s. 666-678
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Tidskriftsartikel (refereegranskat)abstract
- Developmental and epileptic encephalopathies (DEEs) are severe neurodevelopmental disorders often beginning in infancy or early childhood that are characterized by intractable seizures, abundant epileptiform activity on EEG, and developmental impairment or regression. CACNA1E is highly expressed in the central nervous system and encodes the alpha(1)-subunit of the voltage-gated Ca(V)2.3 channel, which conducts high voltage-activated R-type calcium currents that initiate synaptic transmission. Using next-generation sequencing techniques, we identified de novo CACNA1E variants in 30 individuals with DEE, characterized by refractory infantile-onset seizures, severe hypotonia, and profound developmental impairment, often with congenital contractures, macrocephaly, hyperkinetic movement disorders, and early death. Most of the 14, partially recurring, variants cluster within the cytoplasmic ends of all four S6 segments, which form the presumed Ca(V)2.3 channel activation gate. Functional analysis of several S6 variants revealed consistent gain-of-function effects comprising facilitated voltage-dependent activation and slowed inactivation. Another variant located in the domain II S4-S5 linker results in facilitated activation and increased current density. Five participants achieved seizure freedom on the anti-epileptic drug topiramate, which blocks R-type calcium channels. We establish pathogenic variants in CACNA1E as a cause of DEEs and suggest facilitated R-type calcium currents as a disease mechanism for human epilepsy and developmental disorders.
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| 16. |
- Houssami, Nehmat, et al.
(författare)
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Interval breast cancer rates for digital breast tomosynthesis versus digital mammography population screening : An individual participant data meta-analysis
- 2021
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Ingår i: EClinicalMedicine. - : Elsevier BV. - 2589-5370. ; 34
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Tidskriftsartikel (refereegranskat)abstract
- Background: Digital breast tomosynthesis (DBT) improves breast cancer (BC) detection compared to mammography, however, it is unknown whether this reduces interval cancer rate (ICR) at follow-up. Methods: Using individual participant data (IPD) from DBT screening studies (identified via periodic literature searches July 2016 to November 2019) we performed an IPD meta-analysis. We estimated ICR for DBT-screened participants and the difference in pooled ICR for DBT and mammography-only screening, and compared interval BC characteristics. Two-stage meta-analysis (study-specific estimation, pooled synthesis) of ICR included random-effects, adjusting for study and age, and was estimated in age and density subgroups. Comparative screening sensitivity was calculated using screen-detected and interval BC data. Findings: Four prospective DBT studies, from European population-based programs, contributed IPD for 66,451 DBT-screened participants: age-adjusted pooled ICR was 13.17/10,000 (95%CI: 8.25–21.02). Pooled ICR was higher in the high-density (21.08/10,000; 95%CI: 6.71–66.27) than the low-density (8.63/10,000; 95%CI: 5.25–14.192) groups (P = 0.03) however estimates did not differ across age-groups (P = 0.32). Based on two studies that also provided data for 153,800 mammography screens (age-adjusted ICR 17.69/10,000; 95%CI: 13.22–23.66), DBT's pooled ICR was 16.83/10,000 (95%CI: 11.89–23.82). Comparative meta-analysis showed a non-significant difference in ICR (-0.44/10,000; 95%CI: -11.00–10.11) and non-significant difference in screening sensitivity (6.79%; 95%CI: -0.73–14.87%) between DBT and DM but a significant pooled difference in cancer detection rate of 33.49/10,000 (95%CI: 23.88–43.10). Distribution of interval BC prognostic characteristics did not differ between screening modalities except that those occurring in DBT-screened participants were significantly more likely to be negative for axillary-node metastases (P = 0.005). Interpretation: Although heterogeneity in ICR estimates and few datasets limit recommendations, there was no difference between DBT and mammography in pooled ICR despite DBT increasing cancer detection.
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| 17. |
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| 18. |
- Knot, J, et al.
(författare)
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How to set up an effective national primary angioplasty network : Lessons learned from five European countries
- 2009
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Ingår i: EuroIntervention. - 1774-024X. ; 3:299, s. 301-309
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Tidskriftsartikel (refereegranskat)abstract
- AIMS: Percutaneous coronary interventions (PCI) are used to treat acute and chronic forms of coronary artery disease. While in chronic forms the main goal of PCI is to improve the quality of life, in acute coronary syndromes (ACS) timely PCI is a life-saving procedure - especially in the setting of ST-elevation myocardial infarction (STEMI). The aim of this study was to describe the experience of countries with successful nationwide implementation of PCI in STEMI, and to provide general recommendations for other countries. METHODS AND RESULTS: The European Association of Percutaneous Cardiovascular Interventions (EAPCI) recenty launched the Stent For Life Initiative (SFLI). The initial phase of this pan-European project was focused on the positive experience of five countries to provide the best practice examples. The Netherlands, the Czech Republic, Sweden, Denmark and Austria were visited and the logistics of ACS treatment was studied. Public campaigns improved patient access to acute PCI. Regional networks involving emergency medical services (EMS), non-PCI hospitals and PCI centres are useful in providing access to acute PCI for most patients. Direct transfer from the first medical contact site to the cathlab is essential to minimise the time delays. Cathlab staff work is organised to provide acute PCI services 24 hours a day / seven days a week (24/7). Even in those regions where thrombolysis is still used due to long transfer distances to PCI, patients should still be transferred to a PCI centre (after thrombolysis). The highest risk non-ST elevation acute myocardial infarction patients should undergo emergency coronary angiography within two hours of hospital admission, i.e. similar to STEMI patients. CONCLUSIONS: Three realistic goals for other countries were defined based on these experiences: 1) primary PCI should be used for >70% of all STEMI patients, 2) primary PCI rates should reach >600 per million inhabitants per year and 3) existing PCI centres should treat all their STEMI patients by primary PCI, i.e. should offer a 24/7 service
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| 19. |
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| 20. |
- Soerensen, Anne L., et al.
(författare)
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A mass budget for mercury and methylmercury in the Arctic Ocean
- 2016
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Ingår i: Global Biogeochemical Cycles. - 0886-6236 .- 1944-9224. ; 30:4, s. 560-575
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Tidskriftsartikel (refereegranskat)abstract
- Elevated biological concentrations of methylmercury (MeHg), a bioaccumulative neurotoxin, are observed throughout the Arctic Ocean, but major sources and degradation pathways in seawater are not well understood. We develop a mass budget for mercury species in the Arctic Ocean based on available data since 2004 and discuss implications and uncertainties. Our calculations show that high total mercury (Hg) in Arctic seawater relative to other basins reflect large freshwater inputs and sea ice cover that inhibits losses through evasion. We find that most net MeHg production (20Mga(-1)) occurs in the subsurface ocean (20-200m). There it is converted to dimethylmercury (Me2Hg: 17Mga(-1)), which diffuses to the polar mixed layer and evades to the atmosphere (14Mga(-1)). Me2Hg has a short atmospheric lifetime and rapidly degrades back to MeHg. We postulate that most evaded Me2Hg is redeposited as MeHg and that atmospheric deposition is the largest net MeHg source (8Mga(-1)) to the biologically productive surface ocean. MeHg concentrations in Arctic Ocean seawater are elevated compared to lower latitudes. Riverine MeHg inputs account for approximately 15% of inputs to the surface ocean (2.5Mga(-1)) but greater importance in the future is likely given increasing freshwater discharges and permafrost melt. This may offset potential declines driven by increasing evasion from ice-free surface waters. Geochemical model simulations illustrate that for the most biologically relevant regions of the ocean, regulatory actions that decrease Hg inputs have the capacity to rapidly affect aquatic Hg concentrations.
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| 21. |
- Soerensen, Anne L., et al.
(författare)
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Four Decades of Spatiotemporal Variability of Per- and Polyfluoroalkyl Substances (PFASs) in the Baltic Sea
- 2024
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Ingår i: Environmental Science and Technology. - 0013-936X .- 1520-5851. ; 58:24, s. 10806-10816
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Tidskriftsartikel (refereegranskat)abstract
- Temporal and spatial variability of per- and polyfluoroalkyl substances (PFASs) in herring, cod, eelpout, and guillemot covering four decades and more than 1000 km in the Baltic Sea was investigated to evaluate the effect of PFAS regulations and residence times of PFASs. Overall, PFAS concentrations responded rapidly to recent regulations but with some notable basin- and homologue-specific variability. The well-ventilated Kattegat and Bothnian Bay showed a faster log-linear decrease for most PFASs than the Baltic Proper, which lacks a significant loss mechanism. PFOS and FOSA, for example, have decreased with 0–7% y–1 in the Baltic Proper and 6–16% y–1 in other basins. PFNA and partly PFOA are exceptions and continue to show stagnant or increasing concentrations. Further, we found that Bothnian Bay herring contained the highest concentrations of >C12 perfluoroalkyl carboxylic acids (PFCAs), likely from rivers with high loads of dissolved organic carbon. In the Kattegat, low PFAS concentrations, but a high FOSA fraction, could be due to influence from the North Sea inflow below the halocline and possibly a local source of FOSA and/or isomer-specific biotransformation. This study represents the most comprehensive spatial and temporal investigation of PFASs in Baltic wildlife while providing new insights into cycling of PFASs within the Baltic Sea ecosystem.
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