1. |
- Fallows, Richard A., et al.
(författare)
-
A LOFAR observation of ionospheric scintillation from two simultaneous travelling ionospheric disturbances
- 2020
-
Ingår i: Journal of Space Weather and Space Climate. - : EDP Sciences. - 2115-7251. ; 10
-
Tidskriftsartikel (refereegranskat)abstract
- This paper presents the results from one of the first observations of ionospheric scintillation taken using the Low-Frequency Array (LOFAR). The observation was of the strong natural radio source Cassiopeia A, taken overnight on 18-19 August 2013, and exhibited moderately strong scattering effects in dynamic spectra of intensity received across an observing bandwidth of 10-80 MHz. Delay-Doppler spectra (the 2-D FFT of the dynamic spectrum) from the first hour of observation showed two discrete parabolic arcs, one with a steep curvature and the other shallow, which can be used to provide estimates of the distance to, and velocity of, the scattering plasma. A cross-correlation analysis of data received by the dense array of stations in the LOFAR "core" reveals two different velocities in the scintillation pattern: a primary velocity of similar to 20-40 ms(-1) with a north-west to south-east direction, associated with the steep parabolic arc and a scattering altitude in the F-region or higher, and a secondary velocity of similar to 110 ms(-1) with a north-east to south-west direction, associated with the shallow arc and a scattering altitude in the D-region. Geomagnetic activity was low in the mid-latitudes at the time, but a weak sub-storm at high latitudes reached its peak at the start of the observation. An analysis of Global Navigation Satellite Systems (GNSS) and ionosonde data from the time reveals a larger-scale travelling ionospheric disturbance (TID), possibly the result of the high-latitude activity, travelling in the north-west to south-east direction, and, simultaneously, a smaller-scale TID travelling in a north-east to south-west direction, which could be associated with atmospheric gravity wave activity. The LOFAR observation shows scattering from both TIDs, at different altitudes and propagating in different directions. To the best of our knowledge this is the first time that such a phenomenon has been reported.
|
|
2. |
|
|
3. |
- Abend, Sven, et al.
(författare)
-
Terrestrial very-long-baseline atom interferometry : Workshop summary
- 2024
-
Ingår i: AVS Quantum Science. - : American Institute of Physics (AIP). - 2639-0213. ; 6:2
-
Forskningsöversikt (refereegranskat)abstract
- This document presents a summary of the 2023 Terrestrial Very-Long-Baseline Atom Interferometry Workshop hosted by CERN. The workshop brought together experts from around the world to discuss the exciting developments in large-scale atom interferometer (AI) prototypes and their potential for detecting ultralight dark matter and gravitational waves. The primary objective of the workshop was to lay the groundwork for an international TVLBAI proto-collaboration. This collaboration aims to unite researchers from different institutions to strategize and secure funding for terrestrial large-scale AI projects. The ultimate goal is to create a roadmap detailing the design and technology choices for one or more kilometer--scale detectors, which will be operational in the mid-2030s. The key sections of this report present the physics case and technical challenges, together with a comprehensive overview of the discussions at the workshop together with the main conclusions.
|
|
4. |
- Bergamaschi, Peter, et al.
(författare)
-
European Obspack compilation of atmospheric carbon dioxide data from ICOS and non-ICOS European stations for the period 1972-2023; : obspack_co2_466_GLOBALVIEWplus_v8.0_2023-04-26
- 2023
-
Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- This data package contains high accuracy CO2 dry air mole fractions from 58 ICOS and non-ICOS European observatories at in total 132 observation levels, collected by the ICOS Atmosphere Thematic Centre (ATC) and provided by the station contributors. The package is part of the Globalviewplus v8.0 data product, released in 2022 and is intended for use in carbon cycle inverse modeling, model evaluation, and satellite validation studies. Please report errors and send comments regarding this product to the ObsPack originators. Please read carefully the ObsPack Fair Use statement and cite appropriately. This is the sixth release of the GLOBALVIEWplus (GV+) cooperative data product. Please review the release notes for this product at www.esrl.noaa.gov/gmd/ccgg/obspack/release_notes.html. Metadata for this product are available at https://commons.datacite.org/doi.org/10.18160/CEC4-CAGK. Please visit http://www.gml.noaa.gov/ccgg/obspack/ for more information.
|
|
5. |
- Bergamaschi, Peter, et al.
(författare)
-
Inverse modelling of European CH4 emissions during 2006–2012 using different inverse models and reassessed atmospheric observations
- 2018
-
Ingår i: Atmospheric Chemistry and Physics. - : Copernicus GmbH. - 1680-7324. ; 18:2, s. 901-920
-
Tidskriftsartikel (refereegranskat)abstract
- We present inverse modelling (top down) estimates of European methane (CH4) emissions for 2006–2012 based on a new quality-controlled and harmonised in situ data set from 18 European atmospheric monitoring stations. We applied an ensemble of seven inverse models and performed four inversion experiments, investigating the impact of different sets of stations and the use of a priori information on emissions. The inverse models infer total CH4 emissions of 26.8 (20.2–29.7) Tg CH4 yr−1 (mean, 10th and 90th percentiles from all inversions) for the EU-28 for 2006–2012 from the four inversion experiments. For comparison, total anthropogenic CH4 emissions reported to UNFCCC (bottom up, based on statistical data and emissions factors) amount to only 21.3 Tg CH4 yr−1 (2006) to 18.8 Tg CH4 yr−1 (2012). A potential explanation for the higher range of top-down estimates compared to bottom-up inventories could be the contribution from natural sources, such as peatlands, wetlands, and wet soils. Based on seven different wetland inventories from the Wetland and Wetland CH4 Inter-comparison of Models Project (WETCHIMP), total wetland emissions of 4.3 (2.3–8.2) Tg CH4 yr−1 from the EU-28 are estimated. The hypothesis of significant natural emissions is supported by the finding that several inverse models yield significant seasonal cycles of derived CH4 emissions with maxima in summer, while anthropogenic CH4 emissions are assumed to have much lower seasonal variability. Taking into account the wetland emissions from the WETCHIMP ensemble, the top-down estimates are broadly consistent with the sum of anthropogenic and natural bottom-up inventories. However, the contribution of natural sources and their regional distribution remain rather uncertain. Furthermore, we investigate potential biases in the inverse models by comparison with regular aircraft profiles at four European sites and with vertical profiles obtained during the Infrastructure for Measurement of the European Carbon Cycle (IMECC) aircraft campaign. We present a novel approach to estimate the biases in the derived emissions, based on the comparison of simulated and measured enhancements of CH4 compared to the background, integrated over the entire boundary layer and over the lower troposphere. The estimated average regional biases range between −40 and 20 % at the aircraft profile sites in France, Hungary and Poland.
|
|
6. |
- Besse, Lenka, et al.
(författare)
-
Treatment with HIV-protease inhibitor nelfinavir identifies membrane lipid composition and fluidity as a therapeutic target in advanced multiple myeloma
- 2021
-
Ingår i: Cancer Research. - 0008-5472 .- 1538-7445. ; 81, s. 4581-4593
-
Tidskriftsartikel (refereegranskat)abstract
- The HIV-protease inhibitor nelfinavir has shown broad anticancer activity in various preclinical and clinical contexts.In patients with advanced, proteasome inhibitor (PI)-refractory multiple myeloma, nelfinavir-based therapy resulted in 65% partial response or better, suggesting that this may be a highly active chemotherapeutic option in this setting.The broad anticancer mechanism of action of nelfinavir implies that it interferes with fundamental aspects of cancer cell biology.We combined proteome-wide affinity-purification of nelfinavir-interacting proteins with genome-wide CRISPR/Cas9-based screening to identify protein partners that interact with nelfinavir in an activity-dependent manner alongside candidate genetic contributors affecting nelfinavir cytotoxicity.Nelfinavir had multiple activity-specific binding partners embedded in lipid bilayers of mitochondria and the endoplasmic reticulum.Nelfinavir affected the fluidity and composition of lipid-rich membranes, disrupted mitochondrial respiration, blocked vesicular transport, and affected the function of membrane-embedded drug efflux transporter ABCB1, triggering the integrated stress response.Sensitivity to nelfinavir was dependent on ADIPOR2, which maintains membrane fluidity by promoting fatty acid desaturation and incorporation into phospholipids.Supplementation with fatty acids prevented the nelfinavir-induced effect on mitochondrial metabolism, drug-efflux transporters, and stress-response activation.Conversely, depletion of fatty acids/cholesterol pools by the FDAapproved drug ezetimibe showed a synergistic anticancer activity with nelfinavir in vitro.These results identify the modification of lipid-rich membranes by nelfinavir as a novel mechanism of action to achieve broad anticancer activity, which may be suitable for the treatment of PI-refractory multiple myeloma.
|
|
7. |
- Ding, Yuan C, et al.
(författare)
-
A nonsynonymous polymorphism in IRS1 modifies risk of developing breast and ovarian cancers in BRCA1 and ovarian cancer in BRCA2 mutation carriers
- 2012
-
Ingår i: Cancer Epidemiology, Biomarkers and Prevention. - : American Association for Cancer Research. - 1055-9965 .- 1538-7755. ; 21:8, s. 1362-1370
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: We previously reported significant associations between genetic variants in insulin receptor substrate 1 (IRS1) and breast cancer risk in women carrying BRCA1 mutations. The objectives of this study were to investigate whether the IRS1 variants modified ovarian cancer risk and were associated with breast cancer risk in a larger cohort of BRCA1 and BRCA2 mutation carriers.METHODS: IRS1 rs1801123, rs1330645, and rs1801278 were genotyped in samples from 36 centers in the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). Data were analyzed by a retrospective cohort approach modeling the associations with breast and ovarian cancer risks simultaneously. Analyses were stratified by BRCA1 and BRCA2 status and mutation class in BRCA1 carriers.RESULTS: Rs1801278 (Gly972Arg) was associated with ovarian cancer risk for both BRCA1 (HR, 1.43; 95% confidence interval (CI), 1.06-1.92; P = 0.019) and BRCA2 mutation carriers (HR, 2.21; 95% CI, 1.39-3.52, P = 0.0008). For BRCA1 mutation carriers, the breast cancer risk was higher in carriers with class II mutations than class I mutations (class II HR, 1.86; 95% CI, 1.28-2.70; class I HR, 0.86; 95%CI, 0.69-1.09; P(difference), 0.0006). Rs13306465 was associated with ovarian cancer risk in BRCA1 class II mutation carriers (HR, 2.42; P = 0.03).CONCLUSION: The IRS1 Gly972Arg single-nucleotide polymorphism, which affects insulin-like growth factor and insulin signaling, modifies ovarian cancer risk in BRCA1 and BRCA2 mutation carriers and breast cancer risk in BRCA1 class II mutation carriers.Impact: These findings may prove useful for risk prediction for breast and ovarian cancers in BRCA1 and BRCA2 mutation carriers.
|
|
8. |
- Hamdi, Yosr, et al.
(författare)
-
Association of breast cancer risk in BRCA1 and BRCA2 mutation carriers with genetic variants showing differential allelic expression : identification of a modifier of breast cancer risk at locus 11q22.3
- 2017
-
Ingår i: Breast Cancer Research and Treatment. - : Springer Science and Business Media LLC. - 0167-6806 .- 1573-7217. ; 161:1, s. 117-134
-
Tidskriftsartikel (refereegranskat)abstract
- Purpose: Cis-acting regulatory SNPs resulting in differential allelic expression (DAE) may, in part, explain the underlying phenotypic variation associated with many complex diseases. To investigate whether common variants associated with DAE were involved in breast cancer susceptibility among BRCA1 and BRCA2 mutation carriers, a list of 175 genes was developed based of their involvement in cancer-related pathways. Methods: Using data from a genome-wide map of SNPs associated with allelic expression, we assessed the association of ~320 SNPs located in the vicinity of these genes with breast and ovarian cancer risks in 15,252 BRCA1 and 8211 BRCA2 mutation carriers ascertained from 54 studies participating in the Consortium of Investigators of Modifiers of BRCA1/2. Results: We identified a region on 11q22.3 that is significantly associated with breast cancer risk in BRCA1 mutation carriers (most significant SNP rs228595 p = 7 × 10−6). This association was absent in BRCA2 carriers (p = 0.57). The 11q22.3 region notably encompasses genes such as ACAT1, NPAT, and ATM. Expression quantitative trait loci associations were observed in both normal breast and tumors across this region, namely for ACAT1, ATM, and other genes. In silico analysis revealed some overlap between top risk-associated SNPs and relevant biological features in mammary cell data, which suggests potential functional significance. Conclusion: We identified 11q22.3 as a new modifier locus in BRCA1 carriers. Replication in larger studies using estrogen receptor (ER)-negative or triple-negative (i.e., ER-, progesterone receptor-, and HER2-negative) cases could therefore be helpful to confirm the association of this locus with breast cancer risk.
|
|
9. |
- Heid, Iris M, et al.
(författare)
-
Meta-analysis identifies 13 new loci associated with waist-hip ratio and reveals sexual dimorphism in the genetic basis of fat distribution
- 2010
-
Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 42:11, s. 949-960
-
Tidskriftsartikel (refereegranskat)abstract
- Waist-hip ratio (WHR) is a measure of body fat distribution and a predictor of metabolic consequences independent of overall adiposity. WHR is heritable, but few genetic variants influencing this trait have been identified. We conducted a meta-analysis of 32 genome-wide association studies for WHR adjusted for body mass index (comprising up to 77,167 participants), following up 16 loci in an additional 29 studies (comprising up to 113,636 subjects). We identified 13 new loci in or near RSPO3, VEGFA, TBX15-WARS2, NFE2L3, GRB14, DNM3-PIGC, ITPR2-SSPN, LY86, HOXC13, ADAMTS9, ZNRF3-KREMEN1, NISCH-STAB1 and CPEB4 (P = 1.9 × 10⁻⁹ to P = 1.8 × 10⁻⁴⁰) and the known signal at LYPLAL1. Seven of these loci exhibited marked sexual dimorphism, all with a stronger effect on WHR in women than men (P for sex difference = 1.9 × 10⁻³ to P = 1.2 × 10⁻¹³). These findings provide evidence for multiple loci that modulate body fat distribution independent of overall adiposity and reveal strong gene-by-sex interactions.
|
|
10. |
- Jones, Stephanie H., et al.
(författare)
-
Are organic films from atmospheric aerosol and sea water inert to oxidation by ozone at the air-water interface?
- 2017
-
Ingår i: Atmospheric Environment. - : PERGAMON-ELSEVIER SCIENCE LTD. - 1352-2310 .- 1873-2844. ; 161, s. 274-287
-
Tidskriftsartikel (refereegranskat)abstract
- The heterogeneous oxidation of thin films of organic material extracted from real aerosol and sea-water samples was studied at the air-water interface using X-ray reflectivity. Oxidation of thin films of organic material extracted from real aerosol and sea-water is important in further understanding the impact of coated aerosols on the climate of the Earth. Surface active insoluble organic material extracted from the atmosphere was found to form stable films at the air-water interface (thickness measured as 10-14 nm). On exposure of the films to gas-phase ozone, no reaction (or change in the relative scattering length of the interface) was observed, indicating a potential lack of unsaturated organic material in the samples. Gas chromatography and electrospray ionization mass spectrometry showed the presence of saturated compounds in the samples. It is therefore proposed that the amount of unsaturated compounds as compared to saturated compounds in the atmospheric material is so low that the mass spectrometry analyses, as well as gas-phase oxidation are dominated by saturated material. A reaction was observed on exposure of the same films to aqueous phase hydroxyl and nitrate radicals and a film thinning mechanism is proposed to explain the change in scattering length of the film at the air-water interface. It can be suggested tentatively that oxidation by gas-phase ozone is not important in the atmosphere for organic films on aqueous atmospheric aerosol and that further studies should focus on radical induced oxidation of saturated organic material instead of unsaturated proxies that are typically studied.
|
|
11. |
- Lango Allen, Hana, et al.
(författare)
-
Hundreds of variants clustered in genomic loci and biological pathways affect human height.
- 2010
-
Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 467:7317, s. 832-8
-
Tidskriftsartikel (refereegranskat)abstract
- Most common human traits and diseases have a polygenic pattern of inheritance: DNA sequence variants at many genetic loci influence the phenotype. Genome-wide association (GWA) studies have identified more than 600 variants associated with human traits, but these typically explain small fractions of phenotypic variation, raising questions about the use of further studies. Here, using 183,727 individuals, we show that hundreds of genetic variants, in at least 180 loci, influence adult height, a highly heritable and classic polygenic trait. The large number of loci reveals patterns with important implications for genetic studies of common human diseases and traits. First, the 180 loci are not random, but instead are enriched for genes that are connected in biological pathways (P = 0.016) and that underlie skeletal growth defects (P<0.001). Second, the likely causal gene is often located near the most strongly associated variant: in 13 of 21 loci containing a known skeletal growth gene, that gene was closest to the associated variant. Third, at least 19 loci have multiple independently associated variants, suggesting that allelic heterogeneity is a frequent feature of polygenic traits, that comprehensive explorations of already-discovered loci should discover additional variants and that an appreciable fraction of associated loci may have been identified. Fourth, associated variants are enriched for likely functional effects on genes, being over-represented among variants that alter amino-acid structure of proteins and expression levels of nearby genes. Our data explain approximately 10% of the phenotypic variation in height, and we estimate that unidentified common variants of similar effect sizes would increase this figure to approximately 16% of phenotypic variation (approximately 20% of heritable variation). Although additional approaches are needed to dissect the genetic architecture of polygenic human traits fully, our findings indicate that GWA studies can identify large numbers of loci that implicate biologically relevant genes and pathways.
|
|
12. |
- Lee, Wai Tung, et al.
(författare)
-
Polarisation Development at the European Spallation Source
- 2023
-
Ingår i: EPJ Web of Conferences. - 2100-014X. ; 286, s. 03004-03004
-
Tidskriftsartikel (refereegranskat)abstract
- To meet the ever-increasing user demand, eleven of the fifteen European Spallation Source (ESS) instruments under construction aim to offer polarised neutrons for user experiments. They include an imaging instrument, a SANS instruments, two reflectometers, three diffractometers, and four spectrometers. In conjunction with in-kind contributions and instrumentation grants, the ESS Polarisation Project will support the incorporation of polarisation analysis on eight of the eleven instruments. The project aims to deliver polarised neutrons for first-science experiments as instruments enter operation. Different polariser and polarisation analyser techniques will be available to accommodate the specifics of experiments on a given instrument. Polarised 3He neutron spin filter using either Metastable Optical Pumping (MEOP) or Spin-Exchange Optical Pumping (SEOP) techniques will provide shared-use equipment among many instruments, with SEOP’s main application being in situ beam-polarisation. Several instruments will also use polarising-supermirror devices. To provide wide-bandwidth spin-flipping capability to the time-of-flight instruments, Adiabatic Fast Passage (AFP) neutron spin flippers, also known as gradient-field radiofrequency spin flippers will be the main method of choice. Devices based on the same AFP principle will also be used to flip 3He nuclear spins. We are constructing our first 3He polariser setup, including field coils to produce highly uniform magnetic field. Monte Carlo simulations are being done for the supermirror polarisers. To ensure science-focused development, we are working with university partners in doing scientific experiments with polarised neutrons. These are some of the activities developing polarisation analysis for ESS instruments in our project.
|
|
13. |
- Liebens, Veerle R., et al.
(författare)
-
Identification and characterization of an anti-pseudomonal dichlorocarbazol derivative displaying anti-biofilm activity
- 2014
-
Ingår i: Bioorganic & Medicinal Chemistry Letters. - : Elsevier BV. - 0960-894X .- 1464-3405. ; 24:23, s. 5404-5408
-
Tidskriftsartikel (refereegranskat)abstract
- Pseudomonas aeruginosa strains resistant towards all currently available antibiotics are increasingly encountered, raising the need for new anti-pseudomonal drugs. We therefore conducted a medium-throughput screen of a small-molecule collection resulting in the identification of the N-alkylated 3,6-dihalogenocarbazol 1-(sec-butylamino)-3-(3,6-dichloro-9H-carbazol-9-yl)propan-2-ol (MIC = 18.5 ?g mL-1). This compound, compound 1, is bacteriostatic towards a broad spectrum of Gram-positive and Gram-negative pathogens, including P. aeruginosa. Importantly, 1 also eradicates mature biofilms of P. aeruginosa. 1 displays no cytotoxicity against various human cell types, pointing to its potential for further development as a novel antibacterial drug.
|
|
14. |
- Marto, João Pedro, et al.
(författare)
-
Safety and Outcome of Revascularization Treatment in Patients With Acute Ischemic Stroke and COVID-19: The Global COVID-19 Stroke Registry.
- 2023
-
Ingår i: Neurology. - 1526-632X. ; 100:7
-
Tidskriftsartikel (refereegranskat)abstract
- COVID-19-related inflammation, endothelial dysfunction, and coagulopathy may increase the bleeding risk and lower the efficacy of revascularization treatments in patients with acute ischemic stroke (AIS). We aimed to evaluate the safety and outcomes of revascularization treatments in patients with AIS and COVID-19.This was a retrospective multicenter cohort study of consecutive patients with AIS receiving intravenous thrombolysis (IVT) and/or endovascular treatment (EVT) between March 2020 and June 2021 tested for severe acute respiratory syndrome coronavirus 2 infection. With a doubly robust model combining propensity score weighting and multivariate regression, we studied the association of COVID-19 with intracranial bleeding complications and clinical outcomes. Subgroup analyses were performed according to treatment groups (IVT-only and EVT).Of a total of 15,128 included patients from 105 centers, 853 (5.6%) were diagnosed with COVID-19; of those, 5,848 (38.7%) patients received IVT-only and 9,280 (61.3%) EVT (with or without IVT). Patients with COVID-19 had a higher rate of symptomatic intracerebral hemorrhage (SICH) (adjusted OR 1.53; 95% CI 1.16-2.01), symptomatic subarachnoid hemorrhage (SSAH) (OR 1.80; 95% CI 1.20-2.69), SICH and/or SSAH combined (OR 1.56; 95% CI 1.23-1.99), 24-hour mortality (OR 2.47; 95% CI 1.58-3.86), and 3-month mortality (OR 1.88; 95% CI 1.52-2.33). Patients with COVID-19 also had an unfavorable shift in the distribution of the modified Rankin score at 3 months (OR 1.42; 95% CI 1.26-1.60).Patients with AIS and COVID-19 showed higher rates of intracranial bleeding complications and worse clinical outcomes after revascularization treatments than contemporaneous non-COVID-19 patients receiving treatment. Current available data do not allow direct conclusions to be drawn on the effectiveness of revascularization treatments in patients with COVID-19 or to establish different treatment recommendations in this subgroup of patients with ischemic stroke. Our findings can be taken into consideration for treatment decisions, patient monitoring, and establishing prognosis.The study was registered under ClinicalTrials.gov identifier NCT04895462.
|
|
15. |
- Nordanstig, Annika, 1974, et al.
(författare)
-
EndoVAscular treatment and ThRombolysis for Ischemic Stroke Patients (EVA-TRISP) registry: basis and methodology of a pan-European prospective ischaemic stroke revascularisation treatment registry.
- 2021
-
Ingår i: BMJ open. - : BMJ. - 2044-6055. ; 11:8
-
Tidskriftsartikel (refereegranskat)abstract
- The Thrombolysis in Ischemic Stroke Patients (TRISP) collaboration was a concerted effort initiated in 2010 with the purpose to address relevant research questions about the effectiveness and safety of intravenous thrombolysis (IVT). The collaboration also aims to prospectively collect data on patients undergoing endovascular treatment (EVT) and hence the name of the collaboration was changed from TRISP to EVA-TRISP. The methodology of the former TRISP registry for patients treated with IVT has already been published. This paper focuses on describing the EVT part of the registry.All centres committed to collecting predefined variables on consecutive patients prospectively. We aim for accuracy and completeness of the data and to adapt local databases to investigate novel research questions. Herein, we introduce the methodology of a recently constructed academic investigator-initiated open collaboration EVT registry built as an extension of an existing IVT registry in patients with acute ischaemic stroke (AIS).Currently, the EVA-TRISP network includes 20 stroke centres with considerable expertise in EVT and maintenance of high-quality hospital-based registries. Following several successful randomised controlled trials (RCTs), many important clinical questions remain unanswered in the (EVT) field and some of them will unlikely be investigated in future RCTs. Prospective registries with high-quality data on EVT-treated patients may help answering some of these unanswered issues, especially on safety and efficacy of EVT in specific patient subgroups.This collaborative effort aims at addressing clinically important questions on safety and efficacy of EVT in conditions not covered by RCTs. The TRISP registry generated substantial novel data supporting stroke physicians in their daily decision making considering IVT candidate patients. While providing observational data on EVT in daily clinical practice, our future findings may likewise be hypothesis generating for future research as well as for quality improvement (on EVT). The collaboration welcomes participation of further centres willing to fulfill the commitment and the outlined requirements.
|
|
16. |
- Osorio, Ana, et al.
(författare)
-
DNA Glycosylases Involved in Base Excision Repair May Be Associated with Cancer Risk in BRCA1 and BRCA2 Mutation Carriers.
- 2014
-
Ingår i: PLoS Genetics. - : Public Library of Science (PLoS). - 1553-7404. ; 10:4
-
Tidskriftsartikel (refereegranskat)abstract
- Single Nucleotide Polymorphisms (SNPs) in genes involved in the DNA Base Excision Repair (BER) pathway could be associated with cancer risk in carriers of mutations in the high-penetrance susceptibility genes BRCA1 and BRCA2, given the relation of synthetic lethality that exists between one of the components of the BER pathway, PARP1 (poly ADP ribose polymerase), and both BRCA1 and BRCA2. In the present study, we have performed a comprehensive analysis of 18 genes involved in BER using a tagging SNP approach in a large series of BRCA1 and BRCA2 mutation carriers. 144 SNPs were analyzed in a two stage study involving 23,463 carriers from the CIMBA consortium (the Consortium of Investigators of Modifiers of BRCA1 and BRCA2). Eleven SNPs showed evidence of association with breast and/or ovarian cancer at p<0.05 in the combined analysis. Four of the five genes for which strongest evidence of association was observed were DNA glycosylases. The strongest evidence was for rs1466785 in the NEIL2 (endonuclease VIII-like 2) gene (HR: 1.09, 95% CI (1.03-1.16), p = 2.7×10-3) for association with breast cancer risk in BRCA2 mutation carriers, and rs2304277 in the OGG1 (8-guanine DNA glycosylase) gene, with ovarian cancer risk in BRCA1 mutation carriers (HR: 1.12 95%CI: 1.03-1.21, p = 4.8×10-3). DNA glycosylases involved in the first steps of the BER pathway may be associated with cancer risk in BRCA1/2 mutation carriers and should be more comprehensively studied.
|
|
17. |
- Postmus, Iris, et al.
(författare)
-
Pharmacogenetic meta-analysis of genome-wide association studies of LDL cholesterol response to statins.
- 2014
-
Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 5
-
Tidskriftsartikel (refereegranskat)abstract
- Statins effectively lower LDL cholesterol levels in large studies and the observed interindividual response variability may be partially explained by genetic variation. Here we perform a pharmacogenetic meta-analysis of genome-wide association studies (GWAS) in studies addressing the LDL cholesterol response to statins, including up to 18,596 statin-treated subjects. We validate the most promising signals in a further 22,318 statin recipients and identify two loci, SORT1/CELSR2/PSRC1 and SLCO1B1, not previously identified in GWAS. Moreover, we confirm the previously described associations with APOE and LPA. Our findings advance the understanding of the pharmacogenetic architecture of statin response.
|
|
18. |
- Rosental, Arnold, et al.
(författare)
-
Gas sensing properties of epitaxial SnO2 thin films prepared by atomic layer deposition
- 2003
-
Ingår i: Sensors and actuators. B, Chemical. - 0925-4005 .- 1873-3077. ; 93:1-3, s. 552-555
-
Tidskriftsartikel (refereegranskat)abstract
- Undoped SnO2 thin films are grown on α-Al2O3(0 1 2) (r-cut sapphire) substrates by gas phase atomic layer deposition (ALD). Two precursor pairs, SnI4–O2 and SnCl4–H2O2, both new for ALD, are used. The films have a cassiterite structure and are (1 0 1)[0 1 0]cassiterite||(0 1 2)[1 0 0]sapphire oriented. A good epitaxial quality and the conductivity acceptable from the standpoint of semiconductor gas sensors are achieved for ultrathin films grown from SnI4–O2 at 600 °C. The sensitivity of these films to CO in air has a maximum at a thickness of about 10 nm. Response rise and decay times belonging to a several seconds interval are measured. The films are assumed to function as a single grain.
|
|
19. |
- Speliotes, Elizabeth K., et al.
(författare)
-
Association analyses of 249,796 individuals reveal 18 new loci associated with body mass index
- 2010
-
Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 42:11, s. 937-948
-
Tidskriftsartikel (refereegranskat)abstract
- Obesity is globally prevalent and highly heritable, but its underlying genetic factors remain largely elusive. To identify genetic loci for obesity susceptibility, we examined associations between body mass index and ~2.8 million SNPs in up to 123,865 individuals with targeted follow up of 42 SNPs in up to 125,931 additional individuals. We confirmed 14 known obesity susceptibility loci and identified 18 new loci associated with body mass index (P < 5 × 10−8), one of which includes a copy number variant near GPRC5B. Some loci (at MC4R, POMC, SH2B1 and BDNF) map near key hypothalamic regulators of energy balance, and one of these loci is near GIPR, an incretin receptor. Furthermore, genes in other newly associated loci may provide new insights into human body weight regulation.
|
|
20. |
- Stolk, Lisette, et al.
(författare)
-
Meta-analyses identify 13 loci associated with age at menopause and highlight DNA repair and immune pathways
- 2012
-
Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 44:3, s. 260-268
-
Tidskriftsartikel (refereegranskat)abstract
- To newly identify loci for age at natural menopause, we carried out a meta-analysis of 22 genome-wide association studies (GWAS) in 38,968 women of European descent, with replication in up to 14,435 women. In addition to four known loci, we identified 13 loci newly associated with age at natural menopause (at P < 5 × 10(-8)). Candidate genes located at these newly associated loci include genes implicated in DNA repair (EXO1, HELQ, UIMC1, FAM175A, FANCI, TLK1, POLG and PRIM1) and immune function (IL11, NLRP11 and PRRC2A (also known as BAT2)). Gene-set enrichment pathway analyses using the full GWAS data set identified exoDNase, NF-κB signaling and mitochondrial dysfunction as biological processes related to timing of menopause.
|
|
21. |
- Ågerstrand, Marlene, et al.
(författare)
-
Emerging investigator series : use of behavioural endpoints in the regulation of chemicals
- 2020
-
Ingår i: Environmental Science. - : Royal Society of Chemistry (RSC). - 2050-7887 .- 2050-7895. ; 22:1, s. 49-65
-
Tidskriftsartikel (refereegranskat)abstract
- Interest in behavioural ecotoxicology is growing, partly due to technological and computational advances in recording behaviours but also because of improvements of detection capacity facilitating reporting effects at environmentally relevant concentrations. The peer-reviewed literature now contains studies investigating the effects of chemicals, including pesticides and pharmaceuticals, on migration, dispersal, aggression, sociability, reproduction, feeding and anti-predator behaviours in vertebrates and invertebrates. To understand how behavioural studies could be used in regulatory decision-making we: (1) assessed the legal obstacles to using behavioural endpoints in EU chemicals regulation; (2) analysed the known cases of use of behavioural endpoints in EU chemicals regulation; and (3) provided examples of behavioural endpoints of relevance for population level effects. We conclude that the only legal obstacle to the use of behavioural endpoints in EU chemicals regulation is whether an endpoint is considered to be relevant at the population level or not. We also conclude that ecotoxicity studies investigating behavioural endpoints are occasionally used in the EU chemicals regulation, and underscore that behavioural endpoints can be relevant at the population level. To improve the current use of behavioural studies in regulatory decision-making contribution from all relevant stakeholders is required. We have the following recommendations: (1) researchers should conduct robust, well-designed and transparent studies that emphasize the relevance of the study for regulation of chemicals; (2) editors and scientific journals should promote detailed, reliable and clearly reported studies; (3) regulatory agencies and the chemical industry need to embrace new behavioural endpoints of relevance at the population level.
|
|
22. |
- Niemi, MEK, et al.
(författare)
-
- 2021
-
swepub:Mat__t
|
|