| 1. |
- Pierre, M., et al.
(författare)
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The XXL survey : First results and future
- 2017
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Ingår i: Astronomical Notes - Astronomische Nachrichten. - : Wiley-VCH Verlagsgesellschaft. - 0004-6337 .- 1521-3994. ; 338:2-3, s. 334-341
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Tidskriftsartikel (refereegranskat)abstract
- The XXL survey currently covers two 25 deg(2) patches with XMM observations of similar to 10 ks. We summarize the scientific results associated with the first release of the XXL dataset, which occurred in mid-2016. We review several arguments for increasing the survey depth to 40 ks during the next decade of XMM operations. X-ray (z < 2) cluster, (z < 4) active galactic nuclei (AGN), and cosmic background survey science will then benefit from an extraordinary data reservoir. This, combined with deep multi-lambda observations, will lead to solid standalone cosmological constraints and provide a wealth of information on the formation and evolution of AGN, clusters, and the X-ray background. In particular, it will offer a unique opportunity to pinpoint the z > 1 cluster density. It will eventually constitute a reference study and an ideal calibration field for the upcoming eROSITA and Euclid missions.
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| 2. |
- Bar, N., et al.
(författare)
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A reference map of potential determinants for the human serum metabolome
- 2020
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Ingår i: Nature. - : Nature Research. - 0028-0836 .- 1476-4687. ; 588:7836, s. 135-140
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Tidskriftsartikel (refereegranskat)abstract
- The serum metabolome contains a plethora of biomarkers and causative agents of various diseases, some of which are endogenously produced and some that have been taken up from the environment1. The origins of specific compounds are known, including metabolites that are highly heritable2,3, or those that are influenced by the gut microbiome4, by lifestyle choices such as smoking5, or by diet6. However, the key determinants of most metabolites are still poorly understood. Here we measured the levels of 1,251 metabolites in serum samples from a unique and deeply phenotyped healthy human cohort of 491 individuals. We applied machine-learning algorithms to predict metabolite levels in held-out individuals on the basis of host genetics, gut microbiome, clinical parameters, diet, lifestyle and anthropometric measurements, and obtained statistically significant predictions for more than 76% of the profiled metabolites. Diet and microbiome had the strongest predictive power, and each explained hundreds of metabolites—in some cases, explaining more than 50% of the observed variance. We further validated microbiome-related predictions by showing a high replication rate in two geographically independent cohorts7,8 that were not available to us when we trained the algorithms. We used feature attribution analysis9 to reveal specific dietary and bacterial interactions. We further demonstrate that some of these interactions might be causal, as some metabolites that we predicted to be positively associated with bread were found to increase after a randomized clinical trial of bread intervention. Overall, our results reveal potential determinants of more than 800 metabolites, paving the way towards a mechanistic understanding of alterations in metabolites under different conditions and to designing interventions for manipulating the levels of circulating metabolites.
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| 3. |
- Wilman, H. R., et al.
(författare)
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Genetic studies of abdominal MRI data identify genes regulating hepcidin as major determinants of liver iron concentration
- 2019
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Ingår i: Journal of Hepatology. - : Elsevier. - 0168-8278 .- 1600-0641. ; 71:3, s. 594-602
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Tidskriftsartikel (refereegranskat)abstract
- Background & Aims: Excess liver iron content is common and is linked to the risk of hepatic and extrahepatic diseases. We aimed to identify genetic variants influencing liver iron content and use genetics to understand its link to other traits and diseases. Methods: First, we performed a genome-wide association study (GWAS) in 8,289 individuals from UK Biobank, whose liver iron level had been quantified by magnetic resonance imaging, before validating our findings in an independent cohort (n = 1,513 from IMI DIRECT). Second, we used Mendelian randomisation to test the causal effects of 25 predominantly metabolic traits on liver iron content. Third, we tested phenome-wide associations between liver iron variants and 770 traits and disease outcomes. Results: We identified 3 independent genetic variants (rs1800562 [C282Y] and rs1799945 [H63D] in HFE and rs855791 [V736A] in TMPRSS6) associated with liver iron content that reached the GWAS significance threshold (p <5 × 10−8). The 2 HFE variants account for ∼85% of all cases of hereditary haemochromatosis. Mendelian randomisation analysis provided evidence that higher central obesity plays a causal role in increased liver iron content. Phenome-wide association analysis demonstrated shared aetiopathogenic mechanisms for elevated liver iron, high blood pressure, cirrhosis, malignancies, neuropsychiatric and rheumatological conditions, while also highlighting inverse associations with anaemias, lipidaemias and ischaemic heart disease. Conclusion: Our study provides genetic evidence that mechanisms underlying higher liver iron content are likely systemic rather than organ specific, that higher central obesity is causally associated with higher liver iron, and that liver iron shares common aetiology with multiple metabolic and non-metabolic diseases. Lay summary: Excess liver iron content is common and is associated with liver diseases and metabolic diseases including diabetes, high blood pressure, and heart disease. We identified 3 genetic variants that are linked to an increased risk of developing higher liver iron content. We show that the same genetic variants are linked to higher risk of many diseases, but they may also be associated with some health advantages. Finally, we use genetic variants associated with waist-to-hip ratio as a tool to show that central obesity is causally associated with increased liver iron content.
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| 4. |
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| 5. |
- Beal, Jacob, et al.
(författare)
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Robust estimation of bacterial cell count from optical density
- 2020
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Ingår i: Communications Biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 3:1
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Tidskriftsartikel (refereegranskat)abstract
- Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data.
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| 6. |
- Huyghe, Jeroen R., et al.
(författare)
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Discovery of common and rare genetic risk variants for colorectal cancer
- 2019
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Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 51:1, s. 76-
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Tidskriftsartikel (refereegranskat)abstract
- To further dissect the genetic architecture of colorectal cancer (CRC), we performed whole-genome sequencing of 1,439 cases and 720 controls, imputed discovered sequence variants and Haplotype Reference Consortium panel variants into genome-wide association study data, and tested for association in 34,869 cases and 29,051 controls. Findings were followed up in an additional 23,262 cases and 38,296 controls. We discovered a strongly protective 0.3% frequency variant signal at CHD1. In a combined meta-analysis of 125,478 individuals, we identified 40 new independent signals at P < 5 x 10(-8), bringing the number of known independent signals for CRC to similar to 100. New signals implicate lower-frequency variants, Kruppel-like factors, Hedgehog signaling, Hippo-YAP signaling, long noncoding RNAs and somatic drivers, and support a role for immune function. Heritability analyses suggest that CRC risk is highly polygenic, and larger, more comprehensive studies enabling rare variant analysis will improve understanding of biology underlying this risk and influence personalized screening strategies and drug development.
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| 7. |
- van Weeren, R. J., et al.
(författare)
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LOFAR Facet Calibration
- 2016
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Ingår i: Astrophysical Journal, Supplement Series. - : American Astronomical Society. - 1538-4365 .- 0067-0049. ; 223:1
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Tidskriftsartikel (refereegranskat)abstract
- LOFAR, the Low-Frequency Array, is a powerful new radio telescope operating between 10 and 240 MHz. LOFAR allows detailed sensitive high-resolution studies of the low-frequency radio sky. At the same time LOFAR also provides excellent short baseline coverage to map diffuse extended emission. However, producing highquality deep images is challenging due to the presence of direction-dependent calibration errors, caused by imperfect knowledge of the station beam shapes and the ionosphere. Furthermore, the large data volume and presence of station clock errors present additional difficulties. In this paper we present a new calibration scheme, which we name facet calibration, to obtain deep high-resolution LOFAR High Band Antenna images using the Dutch part of the array. This scheme solves and corrects the direction-dependent errors in a number of facets that cover the observed field of view. Facet calibration provides close to thermal noise limited images for a typical 8 hr observing run at similar to 5. resolution, meeting the specifications of the LOFAR Tier-1 northern survey.
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| 8. |
- van Weeren, R. J., et al.
(författare)
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LOFAR, VLA, AND CHANDRA OBSERVATIONS OF THE TOOTHBRUSH GALAXY CLUSTER
- 2016
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Ingår i: Astrophysical Journal. - : American Astronomical Society. - 1538-4357 .- 0004-637X. ; 818:2
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Tidskriftsartikel (refereegranskat)abstract
- We present deep LOFAR observations between 120 and 181 MHz of the "Toothbrush" (RX J0603.3+ 4214), a cluster that contains one of the brightest radio relic sources known. Our LOFAR observations exploit a new and novel calibration scheme to probe 10 times deeper than any previous study in this relatively unexplored part of the spectrum. The LOFAR observations, when combined with VLA, GMRT, and Chandra X-ray data, provide new information about the nature of cluster merger shocks and their role in re-accelerating relativistic particles. We derive a spectral index of alpha = -0.8 +/- 0.1 at the northern edge of the main radio relic, steepening toward the south to alpha approximate to-2. The spectral index of the radio halo is remarkably uniform (alpha = -1.16, with an intrinsic scatter of
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| 9. |
- Ingemarsson, Ingemar, et al.
(författare)
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Effects of isradipine, a new calcium antagonist, on postpartum uterine activity
- 1989
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Ingår i: Acta Obstetricia et Gynecologica Scandinavica. - : Wiley. - 1600-0412 .- 0001-6349. ; 68:8, s. 725-730
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Tidskriftsartikel (refereegranskat)abstract
- The effects of a new calcium antagonist, isradipine (PN 200-110) on postpartum uterine activity and the maternal cardiovascular system were investigated. Uterine activity was recorded by a microtip transducer catheter inserted transcervically within 45 min of normal vaginal delivery. 0.5 mg of isradipine was given as a bolus injection during 5 min to 7 women with spontaneous uterine activity and 1 mg was given during a 15-min period to another 8 women with oxytocin-stimulated uterine activity. Matched controls with similar pre-injection activity (+/- 5%) but not given the drug were selected for comparison. The effects of the drug in 3 women (given 1 mg of isradipine) were compared with those in matched controls and in women given 0.25 mg of terbutalin i.v. as a bolus injection. Isradipine had a marked inhibitory effect on both spontaneous and oxytocin-stimulated uterine activity. The inhibitory effect of 1 mg of isradipine seemed comparable to that of 0.25 mg of terbutalin. The inhibition occurred within 1-2 min after the injection and was sustained throughout the study period (2 h). A transient reduction of the systolic (mean maximum decrease 10-15%) and diastolic blood pressure (mean maximum decrease 15-20%) was seen, particularly during the injection period. Hypotension (systolic blood pressure less than 80 mmHg) was not recorded. A moderate increase in pulse rate (mean maximum increase 22-27%) was seen in all cases. The results show that isradipine given as a bolus injection can inhibit early postpartum uterine activity, with minimal side effects.
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