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- Shrine, N, et al.
(author)
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Multi-ancestry genome-wide association analyses improve resolution of genes and pathways influencing lung function and chronic obstructive pulmonary disease risk
- 2023
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In: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 55:3, s. 410-
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Journal article (peer-reviewed)abstract
- Lung-function impairment underlies chronic obstructive pulmonary disease (COPD) and predicts mortality. In the largest multi-ancestry genome-wide association meta-analysis of lung function to date, comprising 580,869 participants, we identified 1,020 independent association signals implicating 559 genes supported by ≥2 criteria from a systematic variant-to-gene mapping framework. These genes were enriched in 29 pathways. Individual variants showed heterogeneity across ancestries, age and smoking groups, and collectively as a genetic risk score showed strong association with COPD across ancestry groups. We undertook phenome-wide association studies for selected associated variants as well as trait and pathway-specific genetic risk scores to infer possible consequences of intervening in pathways underlying lung function. We highlight new putative causal variants, genes, proteins and pathways, including those targeted by existing drugs. These findings bring us closer to understanding the mechanisms underlying lung function and COPD, and should inform functional genomics experiments and potentially future COPD therapies.
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- Bravo, L, et al.
(author)
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- 2021
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swepub:Mat__t
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- Tabiri, S, et al.
(author)
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- 2021
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swepub:Mat__t
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| 11. |
- Artigas, MS, et al.
(author)
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Sixteen new lung function signals identified through 1000 Genomes Project reference panel imputation
- 2015
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In: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 6, s. 8658-
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Journal article (peer-reviewed)abstract
- Lung function measures are used in the diagnosis of chronic obstructive pulmonary disease. In 38,199 European ancestry individuals, we studied genome-wide association of forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) and FEV1/FVC with 1000 Genomes Project (phase 1)-imputed genotypes and followed up top associations in 54,550 Europeans. We identify 14 novel loci (P<5 × 10−8) in or near ENSA, RNU5F-1, KCNS3, AK097794, ASTN2, LHX3, CCDC91, TBX3, TRIP11, RIN3, TEKT5, LTBP4, MN1 and AP1S2, and two novel signals at known loci NPNT and GPR126, providing a basis for new understanding of the genetic determinants of these traits and pulmonary diseases in which they are altered.
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- Hu, X., et al.
(author)
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Thermal modelling of water activity on comet 67P/Churyumov-Gerasimenko with global dust mantle and plural dust-to-ice ratio
- 2017
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In: Monthly notices of the Royal Astronomical Society. - : OXFORD UNIV PRESS. - 0035-8711 .- 1365-2966. ; 469, s. S295-S311
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Journal article (peer-reviewed)abstract
- We perform a thermo-physical analysis on water activity of comet 67P/Churyumov-Gerasimenko (67P). The sublimation of water is assumed to occur from beneath a global, desiccated dust mantle over the irregular-shaped nucleus. The concept of two thermal models, the recipe of model formulation and the strategy of application to comet 67P are described. For an accurate and efficient evaluation of energy input by insolation and self-heating over the nucleus, a Landscape data base is devised based on polyhedral shape models of the nucleus. We apply the thermal models to investigate the impact of certain parameters of nucleus properties on water production. It is found that the measured water production of 67P can be overall attributed to sublimation of water ice with a mass abundance of a few to 10 per cent beneath a uniform dust mantle of several millimetres to one centimetre in thickness. Insofar as 67P is concerned, we argue against the necessity to invoke assumptions on localized water activity, or on the distinction of active/dormant surface areas.
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- Khatri, C, et al.
(author)
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Outcomes after perioperative SARS-CoV-2 infection in patients with proximal femoral fractures: an international cohort study
- 2021
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In: BMJ open. - : BMJ. - 2044-6055. ; 11:11, s. e050830-
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Journal article (peer-reviewed)abstract
- Studies have demonstrated high rates of mortality in people with proximal femoral fracture and SARS-CoV-2, but there is limited published data on the factors that influence mortality for clinicians to make informed treatment decisions. This study aims to report the 30-day mortality associated with perioperative infection of patients undergoing surgery for proximal femoral fractures and to examine the factors that influence mortality in a multivariate analysis.SettingProspective, international, multicentre, observational cohort study.ParticipantsPatients undergoing any operation for a proximal femoral fracture from 1 February to 30 April 2020 and with perioperative SARS-CoV-2 infection (either 7 days prior or 30-day postoperative).Primary outcome30-day mortality. Multivariate modelling was performed to identify factors associated with 30-day mortality.ResultsThis study reports included 1063 patients from 174 hospitals in 19 countries. Overall 30-day mortality was 29.4% (313/1063). In an adjusted model, 30-day mortality was associated with male gender (OR 2.29, 95% CI 1.68 to 3.13, p<0.001), age >80 years (OR 1.60, 95% CI 1.1 to 2.31, p=0.013), preoperative diagnosis of dementia (OR 1.57, 95% CI 1.15 to 2.16, p=0.005), kidney disease (OR 1.73, 95% CI 1.18 to 2.55, p=0.005) and congestive heart failure (OR 1.62, 95% CI 1.06 to 2.48, p=0.025). Mortality at 30 days was lower in patients with a preoperative diagnosis of SARS-CoV-2 (OR 0.6, 95% CI 0.6 (0.42 to 0.85), p=0.004). There was no difference in mortality in patients with an increase to delay in surgery (p=0.220) or type of anaesthetic given (p=0.787).ConclusionsPatients undergoing surgery for a proximal femoral fracture with a perioperative infection of SARS-CoV-2 have a high rate of mortality. This study would support the need for providing these patients with individualised medical and anaesthetic care, including medical optimisation before theatre. Careful preoperative counselling is needed for those with a proximal femoral fracture and SARS-CoV-2, especially those in the highest risk groups.Trial registration numberNCT04323644
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| 18. |
- La Forgia, F., et al.
(author)
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Geomorphology and spectrophotometry of Philae's landing site on comet 67P/Churyumov-Gerasimenko
- 2015
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In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 583
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Journal article (peer-reviewed)abstract
- Context. On 12 November 2014 the European mission Rosetta succeeded in delivering a lander, named Philae, on the surface of one of the smallest, low-gravity and most primitive bodies of the solar system, the comet 67P/Churyumov-Gerasimenko (67P). Aims. The aim of this paper is to provide a comprehensive geomorphological and spectrophotometric analysis of Philae's landing site (Agilkia) to give an essential framework for the interpretation of its in situ measurements. Methods. OSIRIS images, coupled with gravitational slopes derived from the 3D shape model based on stereo-photogrammetry were used to interpret the geomorphology of the site. We adopted the Hapke model, using previously derived parameters, to photometrically correct the images in orange filter (649.2 nm). The best approximation to the Hapke model, given by the Akimov parameter-less function, was used to correct the reflectance for the effects of viewing and illumination conditions in the other filters. Spectral analyses on coregistered color cubes were used to retrieve spectrophotometric properties. Results. The landing site shows an average normal albedo of 6.7% in the orange filter with variations of similar to 15% and a global featureless spectrum with an average red spectral slope of 15.2%/100 nm between 480.7 nm (blue filter) and 882.1 nm (near-IR filter). The spatial analysis shows a well-established correlation between the geomorphological units and the photometric characteristics of the surface. In particular, smooth deposits have the highest reflectance a bluer spectrum than the outcropping material across the area. Conclusions. The featureless spectrum and the redness of the material are compatible with the results by other instruments that have suggested an organic composition. The observed small spectral variegation could be due to grain size effects. However, the combination of photometric and spectral variegation suggests that a compositional differentiation is more likely. This might be tentatively interpreted as the effect of the efficient dust-transport processes acting on 67P. High-activity regions might be the original sources for smooth fine-grained materials that then covered Agilkia as a consequence of airfall of residual material. More observations performed by OSIRIS as the comet approaches the Sun would help interpreting the processes that work at shaping the landing site and the overall nucleus.
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- Masoumzadeh, N., et al.
(author)
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Opposition effect on comet 67P/Churyumov-Gerasimenko using Rosetta-OSIRIS images
- 2017
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In: Astronomy and Astrophysics. - : EDP SCIENCES S A. - 0004-6361 .- 1432-0746. ; 599
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Journal article (peer-reviewed)abstract
- Aims. We aim to explore the behavior of the opposition effect as an important tool in optical remote sensing on the nucleus of comet 67P/Churyumov-Gerasimenko (67P), using Rosetta-OSIRIS images acquired in different filters during the approach phase, July-August 2014 and the close flyby images on 14 of February 2015, which contain the spacecraft shadow. Methods. We based our investigation on the global and local brightness from the surface of 67P with respect to the phase angle, also known as phase curve. The local phase curve corresponds to a region that is located at the Imhotep-Ash boundary of 67P. Assuming that the region at the Imhotep-Ash boundary and the entire nucleus have similar albedo, we combined the global and local phase curves to study the opposition-surge morphology and constrain the structure and properties of 67P. The model parameters were furthermore compared with other bodies in the solar system and existing laboratory study. Results. We found that the morphological parameters of the opposition surge decrease monotonically with wavelength, whereas in the case of coherent backscattering this behavior should be the reverse. The results from comparative analysis place 67P in the same category as the two Mars satellites, Phobos and Deimos, which are notably different from all airless bodies in the solar system. The similarity between the surface phase function of 67P and a carbon soot sample at extremely small angles is identified, introducing regolith at the boundary of the Imhotep-Ash region of 67P as a very dark and fluffy layer.
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- Oklay, N., et al.
(author)
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Comparative study of water ice exposures on cometary nuclei using multispectral imaging data
- 2016
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In: Monthly notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 462, s. S394-S414
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Journal article (peer-reviewed)abstract
- Deep Impact, EPOXI and Rosetta missions visited comets 9P/Tempel 1, 103P/Hartley 2 and 67P/Churyumov-Gerasimenko, respectively. Each of these three missions was equipped with both multispectral imagers and infrared spectrometers. Bright blue features containing water ice were detected in each of these comet nuclei. We analysed multispectral properties of enriched water ice features observed via Optical, Spectroscopic, and Infrared Remote Imaging System narrow angle camera on comet 67P in the wavelength range of 260-1000 nm and then compared with multispectral data of water ice deposits observed on comets 9P and 103P. We characterize the UV/VIS properties of water-ice-rich features observed on the nuclei of these three comets. When compared to the average surface of each comet, our analysis shows that the water ice deposits seen on comet 9P are similar to the clustered water-ice-rich features seen on comet 67P, while the water ice deposit seen on comet 103P is more akin to two large isolated water-ice-rich features seen on comet 67P. Our results indicate that the water ice deposit observed on comet 103P contains more water ice than the water-ice-rich features observed on comets 9P and 67P, proportionally to the average surface of each nucleus.
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