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- Cicardi, M., et al.
(author)
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Icatibant, a New Bradykinin-Receptor Antagonist, in Hereditary Angioedema
- 2010
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In: New England Journal of Medicine. - 0028-4793. ; 363:6, s. 532-541
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Journal article (peer-reviewed)abstract
- BACKGROUND Hereditary angioedema is characterized by recurrent attacks of angioedema of the skin, larynx, and gastrointestinal tract. Bradykinin is the key mediator of symptoms. Icatibant is a selective bradykinin B2 receptor antagonist. METHODS In two double-blind, randomized, multicenter trials, we evaluated the effect of icatibant in patients with hereditary angioedema presenting with cutaneous or abdominal attacks. In the For Angioedema Subcutaneous Treatment (FAST) 1 trial, patients received either icatibant or placebo; in FAST-2, patients received either icatibant or oral tranexamic acid, at a dose of 3 g daily for 2 days. Icatibant was given once, subcutaneously, at a dose of 30 mg. The primary end point was the median time to clinically significant relief of symptoms. RESULTS A total of 56 and 74 patients underwent randomization in the FAST-1 and FAST-2 trials, respectively. The primary end point was reached in 2.5 hours with icatibant versus 4.6 hours with placebo in the FAST-1 trial (P=0.14) and in 2.0 hours with icatibant versus 12.0 hours with tranexamic acid in the FAST-2 trial (P<0.001). In the FAST-1 study, 3 recipients of icatibant and 13 recipients of placebo needed treatment with rescue medication. The median time to first improvement of symptoms, as assessed by patients and by investigators, was significantly shorter with icatibant in both trials. No icatibant-related serious adverse events were reported. CONCLUSIONS In patients with hereditary angioedema having acute attacks, we found a significant benefit of icatibant as compared with tranexamic acid in one trial and a nonsignificant benefit of icatibant as compared with placebo in the other trial with regard to the primary end point. The early use of rescue medication may have obscured the benefit of icatibant in the placebo trial. (Funded by Jerini; ClinicalTrials.gov numbers, NCT00097695 and NCT00500656.)
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- Güsten, R., et al.
(author)
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APEX - The Atacama Pathfinder Experiment
- 2006
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In: Proceedings of SPIE - The International Society for Optical Engineering. - : SPIE. - 0277-786X .- 1996-756X. ; 6267 I
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Conference paper (peer-reviewed)abstract
- APEX, the Atacama Pathfinder Experiment, has been successfully commissioned and is in operation now. This novel submillimeter telescope is located at 5107 m altitude on Llano de Chajnantor in the Chilean High Andes, on what is considered one of the world's outstanding sites for submillimeter astronomy. The primary reflector with 12 m diameter has been carefully adjusted by means of holography. Its surface smoothness of 17-18 μm makes APEX suitable for observations up to 200 μm, through all atmospheric submm windows accessible from the ground.
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- Martin, S., et al.
(author)
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ALCHEMI, an ALMA Comprehensive High-resolution Extragalactic Molecular Inventory: Survey presentation and first results from the ACA array
- 2021
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In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 656
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Journal article (peer-reviewed)abstract
- Context. The interstellar medium is the locus of physical processes affecting the evolution of galaxies which drive or are the result of star formation activity, supermassive black hole growth, and feedback. The resulting physical conditions determine the observable chemical abundances that can be explored through molecular emission observations at millimeter and submillimeter wavelengths. Aims. Our goal is to unveiling the molecular richness of the central region of the prototypical nearby starburst galaxy NGC 253 at an unprecedented combination of sensitivity, spatial resolution, and frequency coverage. Methods. We used the Atacama Large Millimeter/submillimeter Array (ALMA), covering a nearly contiguous 289 GHz frequency range between 84.2 and 373.2 GHz, to image the continuum and spectral line emission at 1.6″(∼28 pc) resolution down to a sensitivity of 30 - 50 mK. This article describes the ALMA Comprehensive High-resolution Extragalactic Molecular Inventory (ALCHEMI) large program. We focus on the analysis of the spectra extracted from the 15″ (∼255 pc) resolution ALMA Compact Array data. Results. We modeled the molecular emission assuming local thermodynamic equilibrium with 78 species being detected. Additionally, multiple hydrogen and helium recombination lines are identified. Spectral lines contribute 5 to 36% of the total emission in frequency bins of 50 GHz. We report the first extragalactic detections of C2H5OH, HOCN, HC3HO, and several rare isotopologues. Isotopic ratios of carbon, oxygen, sulfur, nitrogen, and silicon were measured with multiple species. Concluison. Infrared pumped vibrationaly excited HCN, HNC, and HC3N emission, originating in massive star formation locations, is clearly detected at low resolution, while we do not detect it for HCO+. We suggest high temperature conditions in these regions driving a seemingly "carbon-rich"chemistry which may also explain the observed high abundance of organic species close to those in Galactic hot cores. The Lvib/LIR ratio was used as a proxy to estimate a 3% contribution from the proto super star cluster to the global infrared emission. Measured isotopic ratios with high dipole moment species agree with those within the central kiloparsec of the Galaxy, while those derived from 13C/18O are a factor of five larger, confirming the existence of multiple interstellar medium components within NGC 253 with different degrees of nucleosynthesis enrichment. The ALCHEMI data set provides a unique template for studies of star-forming galaxies in the early Universe.
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- 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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- Garratt, T. K., et al.
(author)
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The SCUBA-2 Large eXtragalactic Survey: 850 μm map, catalogue and the bright-end number counts of the XMM-LSS field
- 2023
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In: Monthly Notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 520:3, s. 3669-3687
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Journal article (peer-reviewed)abstract
- We present 850 μm imaging of the XMM-LSS field observed for 170 h as part of the James Clerk Maxwell Telescope SCUBA-2 Large eXtragalactic Survey (S2LXS). S2LXS XMM-LSS maps an area of 9 deg2, reaching a moderate depth of 1σ 4 mJy beam−1. This is the largest contiguous area of extragalactic sky mapped by James Clerk Maxwell Telescope (JCMT) at 850 μm to date. The wide area of the S2LXS XMM-LSS survey allows us to probe the ultra-bright (S850μm 15 mJy), yet rare submillimetre population. We present the S2LXS XMM-LSS catalogue, which comprises 40 sources detected at >5σ significance, with deboosted flux densities in the range of 7–48 mJy. We robustly measure the bright-end of the 850 μm number counts at flux densities >7 mJy, reducing the Poisson errors compared to existing measurements. The S2LXS XMM-LSS observed number counts show the characteristic upturn at bright fluxes, expected to be motivated by local sources of submillimetre emission and high-redshift strongly lensed galaxies. We find that the observed 850 μm number counts are best reproduced by model predictions that include either strong lensing or source blending from a 15-arcsec beam, indicating that both may make an important contribution to the observed overabundance of bright single dish 850 μm selected sources. We make the S2LXS XMM-LSS 850 μm map and >5σ catalogue presented here publicly available.
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