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- Hibar, Derrek P., et al.
(author)
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Novel genetic loci associated with hippocampal volume
- 2017
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In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 8
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Journal article (peer-reviewed)abstract
- The hippocampal formation is a brain structure integrally involved in episodic memory, spatial navigation, cognition and stress responsiveness. Structural abnormalities in hippocampal volume and shape are found in several common neuropsychiatric disorders. To identify the genetic underpinnings of hippocampal structure here we perform a genome-wide association study (GWAS) of 33,536 individuals and discover six independent loci significantly associated with hippocampal volume, four of them novel. Of the novel loci, three lie within genes (ASTN2, DPP4 and MAST4) and one is found 200 kb upstream of SHH. A hippocampal subfield analysis shows that a locus within the MSRB3 gene shows evidence of a localized effect along the dentate gyrus, subiculum, CA1 and fissure. Further, we show that genetic variants associated with decreased hippocampal volume are also associated with increased risk for Alzheimer's disease (r(g) = -0.155). Our findings suggest novel biological pathways through which human genetic variation influences hippocampal volume and risk for neuropsychiatric illness.
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| 4. |
- Satizabal, Claudia L., et al.
(author)
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Genetic architecture of subcortical brain structures in 38,851 individuals
- 2019
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In: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 51:11, s. 1624-
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Journal article (peer-reviewed)abstract
- Subcortical brain structures are integral to motion, consciousness, emotions and learning. We identified common genetic variation related to the volumes of the nucleus accumbens, amygdala, brainstem, caudate nucleus, globus pallidus, putamen and thalamus, using genome-wide association analyses in almost 40,000 individuals from CHARGE, ENIGMA and UK Biobank. We show that variability in subcortical volumes is heritable, and identify 48 significantly associated loci (40 novel at the time of analysis). Annotation of these loci by utilizing gene expression, methylation and neuropathological data identified 199 genes putatively implicated in neurodevelopment, synaptic signaling, axonal transport, apoptosis, inflammation/infection and susceptibility to neurological disorders. This set of genes is significantly enriched for Drosophila orthologs associated with neurodevelopmental phenotypes, suggesting evolutionarily conserved mechanisms. Our findings uncover novel biology and potential drug targets underlying brain development and disease.
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| 6. |
- van Weeren, R. J., et al.
(author)
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LOFAR Facet Calibration
- 2016
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In: Astrophysical Journal, Supplement Series. - : American Astronomical Society. - 1538-4365 .- 0067-0049. ; 223:1
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Journal article (peer-reviewed)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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| 7. |
- van Weeren, R. J., et al.
(author)
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LOFAR, VLA, AND CHANDRA OBSERVATIONS OF THE TOOTHBRUSH GALAXY CLUSTER
- 2016
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In: Astrophysical Journal. - : American Astronomical Society. - 1538-4357 .- 0004-637X. ; 818:2
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Journal article (peer-reviewed)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. |
- Asad, K. M. B., et al.
(author)
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Polarization leakage in epoch of reionization windows - I. Low Frequency Array observations of the 3C196 field
- 2015
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In: Monthly notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 451:4, s. 3709-3727
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Journal article (peer-reviewed)abstract
- Detection of the 21-cm signal coming from the epoch of reionization (EoR) is challenging especially because, even after removing the foregrounds, the residual Stokes I maps contain leakage from polarized emission that can mimic the signal. Here, we discuss the instrumental polarization of Low Frequency Array (LOFAR) and present realistic simulations of the leakages between Stokes parameters. From the LOFAR observations of polarized emission in the 3C196 field, we have quantified the level of polarization leakage caused by the nominal model beam of LOFAR, and compared it with the EoR signal using power spectrum analysis. We found that at 134-166 MHz, within the central 4A degrees of the field the (Q, U) -> I leakage power is lower than the EoR signal at k < 0.3 Mpc(-1). The leakage was found to be localized around a Faraday depth of 0, and the rms of the leakage as a fraction of the rms of the polarized emission was shown to vary between 0.2 and 0.3 per cent, both of which could be utilized in the removal of leakage. Moreover, we could define an 'EoR window' in terms of the polarization leakage in the cylindrical power spectrum above the point spread function (PSF)-induced wedge and below k(ayen) similar to 0.5 Mpc(-1), and the window extended up to k(ayen) similar to 1 Mpc(-1) at all k(aSyen) when 70 per cent of the leakage had been removed. These LOFAR results show that even a modest polarimetric calibration over a field of view of a parts per thousand(2) 4A degrees in the future arrays like Square Kilometre Array will ensure that the polarization leakage remains well below the expected EoR signal at the scales of 0.02-1 Mpc(-1).
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| 11. |
- Voorham, Jaco, et al.
(author)
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Real-world effectiveness evaluation of budesonide/formoterol Spiromax for the management of asthma and chronic obstructive pulmonary disease in the UK
- 2018
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In: BMJ Open. - : BMJ. - 2044-6055. ; 8:10
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Journal article (peer-reviewed)abstract
- METHODS: Patients with asthma and/or COPD who switched to BF Spiromax were matched (1:3) with non-switchers. Data were obtained from the Optimum Patient Care Research Database and Clinical Practice Research Datalink in the UK. The primary end point was the proportion of patients achieving disease control (using the risk domain control (RDC) algorithm); secondary end points were: exacerbation rate, short-acting β2-agonist (SABA) use and treatment stability (achieved RDC; no maintenance treatment change). Non-inferiority was defined as having 95% CI lower bound above -10%, using conditional logistic regression and adjusted for relevant confounders.OBJECTIVES: Budesonide/formoterol (BF) Spiromax ® is an inhaled corticosteroid/long-acting β2-agonist fixed-dose combination (FDC) inhaler, designed to minimise common inhaler errors and provide reliable and consistent dose delivery in asthma and chronic obstructive pulmonary disease (COPD). We evaluated non-inferiority of BF Spiromax after changing from another FDC inhaler, compared with continuing the original inhaler.RESULTS: Comparing 385 matched patients (asthma 253; COPD 132) who switched to BF Spiromax with 1091 (asthma 743; COPD 348) non-switchers, non-inferiority of BF Spiromax in RDC was demonstrated (adjusted difference: +6.6%; 95% CI -0.3 to 13.5). Among patients with asthma, switchers to BF Spiromax versus BF Turbuhaler® reported fewer exacerbations (adjusted rate ratio (RR) 0.76;95% CI 0.60 to 0.99; p=0.044); were less likely to use high daily doses of SABA (adjusted OR 0.71;95% CI 0.52 to 0.98; p=0.034); used fewer SABA inhalers (adjusted RR 0.92;95% CI 0.86 to 0.99; p=0.019); and were more likely to achieve treatment stability (adjusted OR 1.44;95% CI 1.02 to 2.04; p=0.037). No significant differences in these end points were seen among patients with COPD.CONCLUSIONS: Among UK patients with asthma and COPD, real-world use of BF Spiromax was non-inferior to BF Turbuhaler in terms of disease control. Among patients with asthma, switching to BF Spiromax was associated with reduced exacerbations, reduced SABA use and improved treatment stability versus continuing on BF Turbuhaler.
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| 12. |
- Zhang, Yao, et al.
(author)
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Spatio-Temporal Convergence of Maximum Daily Light-Use Efficiency Based on Radiation Absorption by Canopy Chlorophyll
- 2018
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In: Geophysical Research Letters. - 0094-8276. ; 45:8, s. 3508-3519
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Journal article (peer-reviewed)abstract
- Light-use efficiency (LUE), which quantifies the plants' efficiency in utilizing solar radiation for photosynthetic carbon fixation, is an important factor for gross primary production estimation. Here we use satellite-based solar-induced chlorophyll fluorescence as a proxy for photosynthetically active radiation absorbed by chlorophyll (APARchl) and derive an estimation of the fraction of APARchl (fPARchl) from four remotely sensed vegetation indicators. By comparing maximum LUE estimated at different scales from 127 eddy flux sites, we found that the maximum daily LUE based on PAR absorption by canopy chlorophyll ( εmaxchl), unlike other expressions of LUE, tends to converge across biome types. The photosynthetic seasonality in tropical forests can also be tracked by the change of fPARchl, suggesting the corresponding εmaxchl to have less seasonal variation. This spatio-temporal convergence of LUE derived from fPARchl can be used to build simple but robust gross primary production models and to better constrain process-based models.
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