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- van Haarlem, M. P., et al.
(författare)
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LOFAR : The LOw-Frequency ARray
- 2013
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 556, s. 1-53
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Tidskriftsartikel (refereegranskat)abstract
- LOFAR, the LOw-Frequency ARray, is a new-generation radio interferometer constructed in the north of the Netherlands and across europe. Utilizing a novel phased-array design, LOFAR covers the largely unexplored low-frequency range from 10–240 MHz and provides a number of unique observing capabilities. Spreading out from a core located near the village of Exloo in the northeast of the Netherlands, a total of 40 LOFAR stations are nearing completion. A further five stations have been deployed throughout Germany, and one station has been built in each of France, Sweden, and the UK. Digital beam-forming techniques make the LOFAR system agile and allow for rapid repointing of the telescope as well as the potential for multiple simultaneous observations. With its dense core array and long interferometric baselines, LOFAR achieves unparalleled sensitivity and angular resolution in the low-frequency radio regime. The LOFAR facilities are jointly operated by the International LOFAR Telescope (ILT) foundation, as an observatory open to the global astronomical community. LOFAR is one of the first radio observatories to feature automated processing pipelines to deliver fully calibrated science products to its user community. LOFAR’s new capabilities, techniques and modus operandi make it an important pathfinder for the Square Kilometre Array (SKA). We give an overview of the LOFAR instrument, its major hardware and software components, and the core science objectives that have driven its design. In addition, we present a selection of new results from the commissioning phase of this new radio observatory.
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- van der Lee, S. J., et al.
(författare)
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A nonsynonymous mutation in PLCG2 reduces the risk of Alzheimer's disease, dementia with Lewy bodies and frontotemporal dementia, and increases the likelihood of longevity
- 2019
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Ingår i: Acta Neuropathologica. - : Springer Science and Business Media LLC. - 0001-6322 .- 1432-0533. ; 138:2, s. 237-250
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Tidskriftsartikel (refereegranskat)abstract
- The genetic variant rs72824905-G (minor allele) in the PLCG2 gene was previously associated with a reduced Alzheimer's disease risk (AD). The role of PLCG2 in immune system signaling suggests it may also protect against other neurodegenerative diseases and possibly associates with longevity. We studied the effect of the rs72824905-G on seven neurodegenerative diseases and longevity, using 53,627 patients, 3,516 long-lived individuals and 149,290 study-matched controls. We replicated the association of rs72824905-G with reduced AD risk and we found an association with reduced risk of dementia with Lewy bodies (DLB) and frontotemporal dementia (FTD). We did not find evidence for an effect on Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS) and multiple sclerosis (MS) risks, despite adequate sample sizes. Conversely, the rs72824905-G allele was associated with increased likelihood of longevity. By-proxy analyses in the UK Biobank supported the associations with both dementia and longevity. Concluding, rs72824905-G has a protective effect against multiple neurodegenerative diseases indicating shared aspects of disease etiology. Our findings merit studying the PLC gamma 2 pathway as drug-target.
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- Schellart, P., et al.
(författare)
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Detecting cosmic rays with the LOFAR radio telescope
- 2013
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 560, s. 1-14
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Tidskriftsartikel (refereegranskat)abstract
- The low frequency array (LOFAR), is the first radio telescope designed with the capability to measure radio emission from cosmic-ray induced air showers in parallel with interferometric observations. In the first ~2 years of observing, 405 cosmic-ray events in the energy range of 1016−1018 eV have been detected in the band from 30−80 MHz. Each of these air showers is registered with up to ~1000 independent antennas resulting in measurements of the radio emission with unprecedented detail. This article describes the dataset, as well as the analysis pipeline, and serves as a reference for future papers based on these data. All steps necessary to achieve a full reconstruction of the electric field at every antenna position are explained, including removal of radio frequency interference, correcting for the antenna response and identification of the pulsed signal.
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- Hagenbeek, FA, et al.
(författare)
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Heritability estimates for 361 blood metabolites across 40 genome-wide association studies
- 2020
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 11:1, s. 39-
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Tidskriftsartikel (refereegranskat)abstract
- Metabolomics examines the small molecules involved in cellular metabolism. Approximately 50% of total phenotypic differences in metabolite levels is due to genetic variance, but heritability estimates differ across metabolite classes. We perform a review of all genome-wide association and (exome-) sequencing studies published between November 2008 and October 2018, and identify >800 class-specific metabolite loci associated with metabolite levels. In a twin-family cohort (N = 5117), these metabolite loci are leveraged to simultaneously estimate total heritability (h2total), and the proportion of heritability captured by known metabolite loci (h2Metabolite-hits) for 309 lipids and 52 organic acids. Our study reveals significant differences in h2Metabolite-hits among different classes of lipids and organic acids. Furthermore, phosphatidylcholines with a high degree of unsaturation have higher h2Metabolite-hits estimates than phosphatidylcholines with low degrees of unsaturation. This study highlights the importance of common genetic variants for metabolite levels, and elucidates the genetic architecture of metabolite classes.
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- Corstanje, A., et al.
(författare)
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The shape of the radio wavefront of extensive air showers as measured with LOFAR
- 2015
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Ingår i: Astroparticle physics. - : Elsevier BV. - 0927-6505 .- 1873-2852. ; 61, s. 22-31
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Tidskriftsartikel (refereegranskat)abstract
- Extensive air showers, induced by high energy cosmic rays impinging on the Earth’s atmosphere, produce radio emission that is measured with the LOFAR radio telescope. As the emission comes from a finite distance of a few kilometers, the incident wavefront is non-planar. A spherical, conical or hyperbolic shape of the wavefront has been proposed, but measurements of individual air showers have been inconclusive so far. For a selected high-quality sample of 161 measured extensive air showers, we have reconstructed the wavefront by measuring pulse arrival times to sub-nanosecond precision in 200 to 350 individual antennas. For each measured air shower, we have fitted a conical, spherical, and hyperboloid shape to the arrival times. The fit quality and a likelihood analysis show that a hyperboloid is the best parameterization. Using a non-planar wavefront shape gives an improved angular resolution, when reconstructing the shower arrival direction. Furthermore, a dependence of the wavefront shape on the shower geometry can be seen. This suggests that it will be possible to use a wavefront shape analysis to get an additional handle on the atmospheric depth of the shower maximum, which is sensitive to the mass of the primary particle.
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| 11. |
- Nelles, A., et al.
(författare)
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Measuring a Cherenkov ring in the radio emission from air showers at 110-190 MHz with LOFAR
- 2015
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Ingår i: Astroparticle physics. - : Elsevier BV. - 0927-6505 .- 1873-2852. ; 65, s. 11-21
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Tidskriftsartikel (refereegranskat)abstract
- Measuring radio emission from air showers offers a novel way to determine properties of the primary cosmic rays such as their mass and energy. Theory predicts that relativistic time compression effects lead to a ring of amplified emission which starts to dominate the emission pattern for frequencies above ∼100∼100 MHz. In this article we present the first detailed measurements of this structure. Ring structures in the radio emission of air showers are measured with the LOFAR radio telescope in the frequency range of 110–190 MHz. These data are well described by CoREAS simulations. They clearly confirm the importance of including the index of refraction of air as a function of height. Furthermore, the presence of the Cherenkov ring offers the possibility for a geometrical measurement of the depth of shower maximum, which in turn depends on the mass of the primary particle.
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- Schweinsberg, Martin, et al.
(författare)
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Same data, different conclusions : Radical dispersion in empirical results when independent analysts operationalize and test the same hypothesis
- 2021
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Ingår i: Organizational Behavior and Human Decision Processes. - : Elsevier BV. - 0749-5978 .- 1095-9920. ; 165, s. 228-249
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Tidskriftsartikel (refereegranskat)abstract
- In this crowdsourced initiative, independent analysts used the same dataset to test two hypotheses regarding the effects of scientists' gender and professional status on verbosity during group meetings. Not only the analytic approach but also the operationalizations of key variables were left unconstrained and up to individual analysts. For instance, analysts could choose to operationalize status as job title, institutional ranking, citation counts, or some combination. To maximize transparency regarding the process by which analytic choices are made, the analysts used a platform we developed called DataExplained to justify both preferred and rejected analytic paths in real time. Analyses lacking sufficient detail, reproducible code, or with statistical errors were excluded, resulting in 29 analyses in the final sample. Researchers reported radically different analyses and dispersed empirical outcomes, in a number of cases obtaining significant effects in opposite directions for the same research question. A Boba multiverse analysis demonstrates that decisions about how to operationalize variables explain variability in outcomes above and beyond statistical choices (e.g., covariates). Subjective researcher decisions play a critical role in driving the reported empirical results, underscoring the need for open data, systematic robustness checks, and transparency regarding both analytic paths taken and not taken. Implications for orga-nizations and leaders, whose decision making relies in part on scientific findings, consulting reports, and internal analyses by data scientists, are discussed.
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- van der Valk, Eline S., et al.
(författare)
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In adults with obesity, copeptin is linked with BMI but is not associated with long-term exposure to cortisol and cortisone
- 2020
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Ingår i: European Journal of Endocrinology. - 1479-683X. ; 183:6, s. 669-676
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Tidskriftsartikel (refereegranskat)abstract
- Context: Obesity and cardiometabolic diseases are associated with higher long-term glucocorticoid levels, measured as scalp hair cortisol (HairF) and cortisone (HairE). Cardiometabolic diseases have also been associated with copeptin, a stable surrogate marker for the arginine-vasopressin (AVP) system. Since AVP is, together with corticotropin-releasing hormone (CRH) an important regulator of the hypothalamic-pituitary adrenal axis (HPA axis), we hypothesize that AVP contributes to chronic hypercortisolism in obesity. Objective: To investigate whether copeptin levels are associated with Higher HairF and HairE levels in obesity. Design: A cross-sectional study in 51 adults with obesity (BMI ≥30 kg/m2). Methods: Associations and interactions between copeptin, HairF, HairE, and cardiometabolic parameters were cross-sectionally analyzed. Results: Copeptin was strongly associated with BMI and waist circumference (WC) (rho = 0.364 and 0.530, P = 0.008 and <0.001, respectively), also after correction for confounders. There were no associations between copeptin and HairF or HairE on a continuous or dichotomized scale, despite correction for confounders. Conclusion: In patients with obesity, AVP seems not a major contributor to the frequently observed high cortisol levels. Other factors which stimulate the HPA axis or affect cortisol synthesis or breakdown may be more important than the influence of AVP on long-term glucocorticoid levels in obesity.
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- Aczel, Balazs, et al.
(författare)
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Consensus-based guidance for conducting and reporting multi-analyst studies
- 2021
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Ingår i: eLIFE. - : eLife Sciences Publications. - 2050-084X. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- Any large dataset can be analyzed in a number of ways, and it is possible that the use of different analysis strategies will lead to different results and conclusions. One way to assess whether the results obtained depend on the analysis strategy chosen is to employ multiple analysts and leave each of them free to follow their own approach. Here, we present consensus-based guidance for conducting and reporting such multi-analyst studies, and we discuss how broader adoption of the multi-analyst approach has the potential to strengthen the robustness of results and conclusions obtained from analyses of datasets in basic and applied research.
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- Goemans, Nathalie M, et al.
(författare)
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Systemic administration of PRO051 in Duchenne's muscular dystrophy.
- 2011
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Ingår i: The New England journal of medicine. - 1533-4406. ; 364:16, s. 1513-22
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Local intramuscular administration of the antisense oligonucleotide PRO051 in patients with Duchenne's muscular dystrophy with relevant mutations was previously reported to induce the skipping of exon 51 during pre-messenger RNA splicing of the dystrophin gene and to facilitate new dystrophin expression in muscle-fiber membranes. The present phase 1-2a study aimed to assess the safety, pharmacokinetics, and molecular and clinical effects of systemically administered PRO051.
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- Zapata, SJ, et al.
(författare)
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GENETIC SUSCEPTIBILITY VARIANTS FOR RHEUMATOID ARTHRITIS ARE NOT ASSOCIATED WITH EARLY REMISSION; A MULTI-COHORT STUDY
- 2021
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Ingår i: ANNALS OF THE RHEUMATIC DISEASES. - : BMJ. - 0003-4967 .- 1468-2060. ; 80, s. 403-404
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Patients who achieve remission promptly could have a specific genetic risk profile that supports regaining immune tolerance. The identification of these genes could provide novel drug targets.Objectives:To test the association between RA genetic risk variants with achieving remission at 6 months.Methods:We computed genetic risk scores (GRS) comprising of the RA susceptibility variants1 and HLA-SE status separately in 4425 patients across eight datasets from inception cohorts. Remission was defined as DAS28CRP<2.6 at 6 months. Missing DAS28CRP values in patients were imputed using predictive mean matching by MICE. We first tested whether baseline DAS28CRP changed with increasing GRS using linear regression. Next, we calculated odds ratios for GRS and HLA-SE on remission using logistic regression. Heterogeneity of the outcome between datasets was mitigated by running inverse variance meta-analysis.Results:Evaluation of the complete dataset, baseline clinical variables did not differ between patients achieving remission and those who did not (Table 1). Distribution of GRS was consistent between datasets. Neither GRS nor HLA-SE was associated with baseline DAS2DAS (OR1.01; 95% CI 0.99-1.04). A fixed effect meta-analysis (Figure 1.) showed no significant effect of the GRS (OR 0.99; 95% CI 0.94-1.03) or HLA-SE (OR 0.8CRP87; 95% CI 0.75-1.01) on remission at 6 months.Table 1.Summary of the data separated by disease activity after 6 months.allRemission at 6 monthsNo remission at 6 monthsN4425*15582430Age, mean (sd)55.38 (13.87)5517 (14.09)55.62 (13.59)Female %68.98%65.43%70.73%ACPA+ %61.94%63.53%61.67%Baseline DAS28, mean (sd)4.76 (1.22)4.47 (1.23)5.1 (1.15)*not all patients had 6 months dataConclusion:In these combined cohorts, RA genetics risk variants are not associated with early disease remission. At baseline there was no difference in genetic risk between patients achieving remission or not. Studies encompassing other genetic variants are needed to elucidate the genetics of RA remission.References:[1]Knevel R et al. Sci Transl Med. 2020;12(545):eaay1548.Acknowledgements:This project has received funding from the Innovative Medicines Initiative 2 Joint Undertaking under grant agreement No 777357, RTCure.This project has received funding from Pfizer Inc.Disclosure of Interests:Samantha Jurado Zapata: None declared, Marc Maurits: None declared, Yann Abraham Employee of: Pfizer, Erik van den Akker: None declared, Anne Barton: None declared, Philip Brown: None declared, Andrew Cope: None declared, Isidoro González-Álvaro: None declared, Carl Goodyear: None declared, Annette van der Helm - van Mil: None declared, Xinli Hu Employee of: Pfizer, Thomas Huizinga: None declared, Martina Johannesson: None declared, Lars Klareskog: None declared, Dennis Lendrem: None declared, Iain McInnes: None declared, Fraser Morton: None declared, Caron Paterson: None declared, Duncan Porter: None declared, Arthur Pratt: None declared, Luis Rodriguez Rodriguez: None declared, Daniela Sieghart: None declared, Paul Studenic: None declared, Suzanne Verstappen: None declared, Leonid Padyukov: None declared, Aaron Winkler Employee of: Pfizer, John D Isaacs: None declared, Rachel Knevel Grant/research support from: Pfizer
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