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- Hayes, MG, et al.
(author)
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Genome-wide association of polycystic ovary syndrome implicates alterations in gonadotropin secretion in European ancestry populations
- 2015
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In: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 6, s. 7502-
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Journal article (peer-reviewed)abstract
- Polycystic ovary syndrome (PCOS) is a common, highly heritable complex disorder of unknown aetiology characterized by hyperandrogenism, chronic anovulation and defects in glucose homeostasis. Increased luteinizing hormone relative to follicle-stimulating hormone secretion, insulin resistance and developmental exposure to androgens are hypothesized to play a causal role in PCOS. Here we map common genetic susceptibility loci in European ancestry women for the National Institutes of Health PCOS phenotype, which confers the highest risk for metabolic morbidities, as well as reproductive hormone levels. Three loci reach genome-wide significance in the case–control meta-analysis, two novel loci mapping to chr 8p23.1 and chr 11p14.1, and a chr 9q22.32 locus previously found in Chinese PCOS. The same chr 11p14.1 SNP, rs11031006, in the region of the follicle-stimulating hormone B polypeptide (FSHB) gene strongly associates with PCOS diagnosis and luteinizing hormone levels. These findings implicate neuroendocrine changes in disease pathogenesis.
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- Maccubbin, D., et al.
(author)
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Lipid-modifying efficacy and tolerability of extended-release niacin/laropiprant in patients with primary hypercholesterolaemia or mixed dyslipidaemia
- 2008
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In: International journal of clinical practice (Esher). - : Hindawi Limited. - 1368-5031 .- 1742-1241. ; 62:12, s. 1959-1970
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Journal article (peer-reviewed)abstract
- Background: Improving lipids beyond low-density lipoprotein cholesterol (LDL-C) lowering with statin monotherapy may further reduce cardiovascular risk. Niacin has complementary lipid-modifying efficacy to statins and cardiovascular benefit, but is underutilised because of flushing, mediated primarily by prostaglandin D2 (PGD2). Laropiprant (LRPT), a PGD 2 receptor (DP1) antagonist that reduces niacin-induced flushing has been combined with extended-release niacin (ERN) into a fixed-dose tablet. Methods and results: Dyslipidaemic patients were randomised to ERN/LRPT 1 g (n = 800), ERN 1 g (n = 543) or placebo (n = 270) for 4 weeks. Doses were doubled (2 tablets/day, i.e. 2 g for active treatments) for 20 weeks. ERN/LRPT 2 g produced significant changes vs. placebo in LDL-C (-18.4%), high-density lipoprotein cholesterol (HDL-C, 20.0%), LDL-C:HDL-C (-31.2%), non-HDL-C (-19.8%), triglycerides (TG, -25.8%), apolipoprotein (Apo) B (-18.8%), Apo A-I (6.9%), total cholesterol (TC, -8.5%), TC:HDL-C (-23.1%) and lipoprotein(a) (-20.8%) across weeks 12-24. ERN/LRPT produced significantly less flushing than ERN during initiation (week 1) and maintenance (weeks 2-24) for all prespecified flushing end-points (incidence, intensity and discontinuation because of flushing). Except for flushing, ERN/LRPT had a safety/tolerability profile comparable with ERN. Conclusion: Extended-release niacin/LRPT 2 g produced significant, durable improvements in multiple lipid/lipoprotein parameters. The improved tolerability of ERN/LRPT supports a simplified 1 g?2 g dosing regimen of niacin, a therapy proven to reduce cardiovascular risk. © 2008 Merck & Co.
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- Sisk-Reynés, Júlia, et al.
(author)
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New constraints on light axion-like particles using Chandra transmission grating spectroscopy of the powerful cluster-hosted quasar H1821+643
- 2022
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In: Monthly notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 510:1, s. 1264-1277
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Journal article (peer-reviewed)abstract
- Axion-like particles (ALPs) are predicted by several Beyond the Standard Model theories, in particular, string theory. In the presence of an external magnetic field perpendicular to the direction of propagation, ALPs can couple to photons. Therefore, if an X-ray source is viewed through a magnetized plasma, such as a luminous quasar in a galaxy cluster, we may expect spectral distortions that are well described by photon–ALP oscillations. We present a 571 ks combined high- and low-energy transmission grating Chandra observation of the powerful radio-quiet quasar H1821+643, hosted by a cool-core cluster at redshift 0.3. The spectrum is well described by a double power-law continuum and broad+narrow iron line emission typical of type-1 active galactic nuclei (AGNs), with remaining spectral features <2.5 per cent<2.5 per cent. Using a cell-based approach to describe the turbulent cluster magnetic field, we compare our spectrum with photon–ALP mixing curves for 500 field realizations, assuming that the thermal-to-magnetic pressure ratio β remains constant up to the virial radius. At 99.7 per cent99.7 per cent credibility and taking β = 100, we exclude all couplings gaγ > 6.3 × 10−13 GeV−1 for most ALP masses <10−12 eV. Our results are moderately more sensitive to constraining ALPs than the best previous result from Chandra observations of the Perseus cluster, albeit with a less constrained field model. We reflect on the promising future of ALP studies with bright AGNs embedded in rich clusters, especially with the upcoming Athena mission.
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