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| 9. |
- Kaptoge, S., et al.
(författare)
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World Health Organization cardiovascular disease risk charts: revised models to estimate risk in 21 global regions
- 2019
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Ingår i: Lancet Global Health. - : Elsevier BV. - 2214-109X. ; 7:10
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Tidskriftsartikel (refereegranskat)abstract
- Background To help adapt cardiovascular disease risk prediction approaches to low-income and middle-income countries, WHO has convened an effort to develop, evaluate, and illustrate revised risk models. Here, we report the derivation, validation, and illustration of the revised WHO cardiovascular disease risk prediction charts that have been adapted to the circumstances of 21 global regions. Methods In this model revision initiative, we derived 10-year risk prediction models for fatal and non-fatal cardiovascular disease (ie, myocardial infarction and stroke) using individual participant data from the Emerging Risk Factors Collaboration. Models included information on age, smoking status, systolic blood pressure, history of diabetes, and total cholesterol. For derivation, we included participants aged 40-80 years without a known baseline history of cardiovascular disease, who were followed up until the first myocardial infarction, fatal coronary heart disease, or stroke event. We recalibrated models using age-specific and sex-specific incidences and risk factor values available from 21 global regions. For external validation, we analysed individual participant data from studies distinct from those used in model derivation. We illustrated models by analysing data on a further 123 743 individuals from surveys in 79 countries collected with the WHO STEPwise Approach to Surveillance. Findings Our risk model derivation involved 376 177 individuals from 85 cohorts, and 19 333 incident cardiovascular events recorded during 10 years of follow-up. The derived risk prediction models discriminated well in external validation cohorts (19 cohorts, 1 096 061 individuals, 25 950 cardiovascular disease events), with Harrell's C indices ranging from 0.685 (95% CI 0 . 629-0 741) to 0.833 (0 . 783-0- 882). For a given risk factor profile, we found substantial variation across global regions in the estimated 10-year predicted risk. For example, estimated cardiovascular disease risk for a 60-year-old male smoker without diabetes and with systolic blood pressure of 140 mm Hg and total cholesterol of 5 mmol/L ranged from 11% in Andean Latin America to 30% in central Asia. When applied to data from 79 countries (mostly low-income and middle-income countries), the proportion of individuals aged 40-64 years estimated to be at greater than 20% risk ranged from less than 1% in Uganda to more than 16% in Egypt. Interpretation We have derived, calibrated, and validated new WHO risk prediction models to estimate cardiovascular disease risk in 21 Global Burden of Disease regions. The widespread use of these models could enhance the accuracy, practicability, and sustainability of efforts to reduce the burden of cardiovascular disease worldwide. Copyright (C) 2019 The Author(s). Published by Elsevier Ltd.
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| 11. |
- Zhou, XP, et al.
(författare)
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Non-coding variability at the APOE locus contributes to the Alzheimer's risk
- 2019
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 3310-
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Tidskriftsartikel (refereegranskat)abstract
- Alzheimer’s disease (AD) is a leading cause of mortality in the elderly. While the coding change of APOE-ε4 is a key risk factor for late-onset AD and has been believed to be the only risk factor in the APOE locus, it does not fully explain the risk effect conferred by the locus. Here, we report the identification of AD causal variants in PVRL2 and APOC1 regions in proximity to APOE and define common risk haplotypes independent of APOE-ε4 coding change. These risk haplotypes are associated with changes of AD-related endophenotypes including cognitive performance, and altered expression of APOE and its nearby genes in the human brain and blood. High-throughput genome-wide chromosome conformation capture analysis further supports the roles of these risk haplotypes in modulating chromatin states and gene expression in the brain. Our findings provide compelling evidence for additional risk factors in the APOE locus that contribute to AD pathogenesis.
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| 12. |
- Romagnoni, A, et al.
(författare)
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Comparative performances of machine learning methods for classifying Crohn Disease patients using genome-wide genotyping data
- 2019
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Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 9:1, s. 10351-
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Tidskriftsartikel (refereegranskat)abstract
- Crohn Disease (CD) is a complex genetic disorder for which more than 140 genes have been identified using genome wide association studies (GWAS). However, the genetic architecture of the trait remains largely unknown. The recent development of machine learning (ML) approaches incited us to apply them to classify healthy and diseased people according to their genomic information. The Immunochip dataset containing 18,227 CD patients and 34,050 healthy controls enrolled and genotyped by the international Inflammatory Bowel Disease genetic consortium (IIBDGC) has been re-analyzed using a set of ML methods: penalized logistic regression (LR), gradient boosted trees (GBT) and artificial neural networks (NN). The main score used to compare the methods was the Area Under the ROC Curve (AUC) statistics. The impact of quality control (QC), imputing and coding methods on LR results showed that QC methods and imputation of missing genotypes may artificially increase the scores. At the opposite, neither the patient/control ratio nor marker preselection or coding strategies significantly affected the results. LR methods, including Lasso, Ridge and ElasticNet provided similar results with a maximum AUC of 0.80. GBT methods like XGBoost, LightGBM and CatBoost, together with dense NN with one or more hidden layers, provided similar AUC values, suggesting limited epistatic effects in the genetic architecture of the trait. ML methods detected near all the genetic variants previously identified by GWAS among the best predictors plus additional predictors with lower effects. The robustness and complementarity of the different methods are also studied. Compared to LR, non-linear models such as GBT or NN may provide robust complementary approaches to identify and classify genetic markers.
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| 14. |
- Brown, A. G. A., et al.
(författare)
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Gaia Data Release 1 Summary of the astrometric, photometric, and survey properties
- 2016
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 595
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Tidskriftsartikel (refereegranskat)abstract
- Context. At about 1000 days after the launch of Gaia we present the first Gaia data release, Gaia DR1, consisting of astrometry and photometry for over 1 billion sources brighter than magnitude 20.7. Aims. A summary of Gaia DR1 is presented along with illustrations of the scientific quality of the data, followed by a discussion of the limitations due to the preliminary nature of this release. Methods. The raw data collected by Gaia during the first 14 months of the mission have been processed by the Gaia Data Processing and Analysis Consortium (DPAC) and turned into an astrometric and photometric catalogue. Results. Gaia DR1 consists of three components: a primary astrometric data set which contains the positions, parallaxes, and mean proper motions for about 2 million of the brightest stars in common with the HIPPARCOS and Tycho-2 catalogues - a realisation of the Tycho-Gaia Astrometric Solution (TGAS) - and a secondary astrometric data set containing the positions for an additional 1.1 billion sources. The second component is the photometric data set, consisting of mean G-band magnitudes for all sources. The G-band light curves and the characteristics of similar to 3000 Cepheid and RR Lyrae stars, observed at high cadence around the south ecliptic pole, form the third component. For the primary astrometric data set the typical uncertainty is about 0.3 mas for the positions and parallaxes, and about 1 mas yr(-1) for the proper motions. A systematic component of similar to 0.3 mas should be added to the parallax uncertainties. For the subset of similar to 94 000 HIPPARCOS stars in the primary data set, the proper motions are much more precise at about 0.06 mas yr(-1). For the secondary astrometric data set, the typical uncertainty of the positions is similar to 10 mas. The median uncertainties on the mean G-band magnitudes range from the mmag level to similar to 0.03 mag over the magnitude range 5 to 20.7. Conclusions. Gaia DR1 is an important milestone ahead of the next Gaia data release, which will feature five-parameter astrometry for all sources. Extensive validation shows that Gaia DR1 represents a major advance in the mapping of the heavens and the availability of basic stellar data that underpin observational astrophysics. Nevertheless, the very preliminary nature of this first Gaia data release does lead to a number of important limitations to the data quality which should be carefully considered before drawing conclusions from the data.
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| 15. |
- Clementini, G., et al.
(författare)
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Testing parallaxes with local Cepheids and RR Lyrae stars
- 2017
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 605
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Tidskriftsartikel (refereegranskat)abstract
- Context. Parallaxes for 331 classical Cepheids, 31 Type II Cepheids, and 364 RR Lyrae stars in common between Gaia and the HIPPARCOS and Tycho-2 catalogues are published in Gaia Data Release 1 (DR1) as part of the Tycho-Gaia Astrometric Solution (TGAS). Aims. In order to test these first parallax measurements of the primary standard candles of the cosmological distance ladder, which involve astrometry collected by Gaia during the initial 14 months of science operation, we compared them with literature estimates and derived new period-luminosity (PL), period-Wesenheit (PW) relations for classical and Type II Cepheids and infrared PL, PL-metallicity (PLZ), and optical luminosity-metallicity (MV-[Fe/H]) relations for the RR Lyrae stars, with zero points based on TGAS.Methods. Classical Cepheids were carefully selected in order to discard known or suspected binary systems. The final sample comprises 102 fundamental mode pulsators with periods ranging from 1.68 to 51.66 days (of which 33 with sigma(omega)/omega < 0 : 5). The Type II Cepheids include a total of 26 W Virginis and BL Herculis stars spanning the period range from 1.16 to 30.00 days (of which only 7 with sigma(omega)/omega 0 : 5). The RR Lyrae stars include 200 sources with pulsation period ranging from 0.27 to 0.80 days (of which 112 with sigma(omega)/omega < 0 : 5). The new relations were computed using multi- band (V; I; J; K-s) photometry and spectroscopic metal abundances available in the literature, and by applying three alternative approaches: (i) linear least-squares fitting of the absolute magnitudes inferred from direct transformation of the TGAS parallaxes; (ii) adopting astrometry-based luminosities; and (iii) using a Bayesian fitting approach. The last two methods work in parallax space where parallaxes are used directly, thus maintaining symmetrical errors and allowing negative parallaxes to be used. The TGAS-based PL; PW; PLZ, and MV [Fe/H] relations are discussed by comparing the distance to the Large Magellanic Cloud provided by different types of pulsating stars and alternative fitting methods.Results. Good agreement is found from direct comparison of the parallaxes of RR Lyrae stars for which both TGAS and HST measurements are available. Similarly, very good agreement is found between the TGAS values and the parallaxes inferred from the absolute magnitudes of Cepheids and RR Lyrae stars analysed with the Baade-Wesselink method. TGAS values also compare favourably with the parallaxes inferred by theoretical model fitting of the multi-band light curves for two of the three classical Cepheids and one RR Lyrae star, which were analysed with this technique in our samples. The K-band PL relations show the significant improvement of the TGAS parallaxes for Cepheids and RR Lyrae stars with respect to the HIPPARCOS measurements. This is particularly true for the RR Lyrae stars for which improvement in quality and statistics is impressive.Conclusions. TGAS parallaxes bring a significant added value to the previous HIPPARCOS estimates. The relations presented in this paper represent the first Gaia-calibrated relations and form a work-in-progress milestone report in the wait for Gaia-only parallaxes of which a first solution will become available with Gaia Data Release 2 (DR2) in 2018.
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| 16. |
- Prusti, T., et al.
(författare)
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The Gaia mission
- 2016
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 595
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Tidskriftsartikel (refereegranskat)abstract
- Gaia is a cornerstone mission in the science programme of the European Space Agency (ESA). The spacecraft construction was approved in 2006, following a study in which the original interferometric concept was changed to a direct-imaging approach. Both the spacecraft and the payload were built by European industry. The involvement of the scientific community focusses on data processing for which the international Gaia Data Processing and Analysis Consortium (DPAC) was selected in 2007. Gaia was launched on 19 December 2013 and arrived at its operating point, the second Lagrange point of the Sun-Earth-Moon system, a few weeks later. The commissioning of the spacecraft and payload was completed on 19 July 2014. The nominal five-year mission started with four weeks of special, ecliptic-pole scanning and subsequently transferred into full-sky scanning mode. We recall the scientific goals of Gaia and give a description of the as-built spacecraft that is currently (mid-2016) being operated to achieve these goals. We pay special attention to the payload module, the performance of which is closely related to the scientific performance of the mission. We provide a summary of the commissioning activities and findings, followed by a description of the routine operational mode. We summarise scientific performance estimates on the basis of in-orbit operations. Several intermediate Gaia data releases are planned and the data can be retrieved from the Gaia Archive, which is available through the Gaia home page.
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| 17. |
- Figlioli, G, et al.
(författare)
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The FANCM:p.Arg658* truncating variant is associated with risk of triple-negative breast cancer
- 2019
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Ingår i: NPJ breast cancer. - : Springer Science and Business Media LLC. - 2374-4677. ; 5, s. 38-
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Tidskriftsartikel (refereegranskat)abstract
- Breast cancer is a common disease partially caused by genetic risk factors. Germline pathogenic variants in DNA repair genes BRCA1, BRCA2, PALB2, ATM, and CHEK2 are associated with breast cancer risk. FANCM, which encodes for a DNA translocase, has been proposed as a breast cancer predisposition gene, with greater effects for the ER-negative and triple-negative breast cancer (TNBC) subtypes. We tested the three recurrent protein-truncating variants FANCM:p.Arg658*, p.Gln1701*, and p.Arg1931* for association with breast cancer risk in 67,112 cases, 53,766 controls, and 26,662 carriers of pathogenic variants of BRCA1 or BRCA2. These three variants were also studied functionally by measuring survival and chromosome fragility in FANCM−/− patient-derived immortalized fibroblasts treated with diepoxybutane or olaparib. We observed that FANCM:p.Arg658* was associated with increased risk of ER-negative disease and TNBC (OR = 2.44, P = 0.034 and OR = 3.79; P = 0.009, respectively). In a country-restricted analysis, we confirmed the associations detected for FANCM:p.Arg658* and found that also FANCM:p.Arg1931* was associated with ER-negative breast cancer risk (OR = 1.96; P = 0.006). The functional results indicated that all three variants were deleterious affecting cell survival and chromosome stability with FANCM:p.Arg658* causing more severe phenotypes. In conclusion, we confirmed that the two rare FANCM deleterious variants p.Arg658* and p.Arg1931* are risk factors for ER-negative and TNBC subtypes. Overall our data suggest that the effect of truncating variants on breast cancer risk may depend on their position in the gene. Cell sensitivity to olaparib exposure, identifies a possible therapeutic option to treat FANCM-associated tumors.
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| 18. |
- Clark, DW, et al.
(författare)
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Associations of autozygosity with a broad range of human phenotypes
- 2019
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 4957-
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Tidskriftsartikel (refereegranskat)abstract
- In many species, the offspring of related parents suffer reduced reproductive success, a phenomenon known as inbreeding depression. In humans, the importance of this effect has remained unclear, partly because reproduction between close relatives is both rare and frequently associated with confounding social factors. Here, using genomic inbreeding coefficients (FROH) for >1.4 million individuals, we show that FROH is significantly associated (p < 0.0005) with apparently deleterious changes in 32 out of 100 traits analysed. These changes are associated with runs of homozygosity (ROH), but not with common variant homozygosity, suggesting that genetic variants associated with inbreeding depression are predominantly rare. The effect on fertility is striking: FROH equivalent to the offspring of first cousins is associated with a 55% decrease [95% CI 44–66%] in the odds of having children. Finally, the effects of FROH are confirmed within full-sibling pairs, where the variation in FROH is independent of all environmental confounding.
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| 19. |
- van Leeuwen, F., et al.
(författare)
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Gaia Data Release 1 : Open cluster astrometry: Performance, limitations, and future prospects
- 2017
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 601
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Tidskriftsartikel (refereegranskat)abstract
- Context. The first Gaia Data Release contains the Tycho-Gaia Astrometric Solution (TGAS). This is a subset of about 2 million stars for which, besides the position and photometry, the proper motion and parallax are calculated using Hipparcos and Tycho-2 positions in 1991.25 as prior information. Aims. We investigate the scientific potential and limitations of the TGAS component by means of the astrometric data for open clusters. Methods. Mean cluster parallax and proper motion values are derived taking into account the error correlations within the astrometric solutions for individual stars, an estimate of the internal velocity dispersion in the cluster, and, where relevant, the effects of the depth of the cluster along the line of sight. Internal consistency of the TGAS data is assessed. Results. Values given for standard uncertainties are still inaccurate and may lead to unrealistic unit-weight standard deviations of least squares solutions for cluster parameters. Reconstructed mean cluster parallax and proper motion values are generally in very good agreement with earlier Hipparcos-based determination, although the Gaia mean parallax for the Pleiades is a significant exception. We have no current explanation for that discrepancy. Most clusters are observed to extend to nearly 15 pc from the cluster centre, and it will be up to future Gaia releases to establish whether those potential cluster-member stars are still dynamically bound to the clusters. Conclusions. The Gaia DR1 provides the means to examine open clusters far beyond their more easily visible cores, and can provide membership assessments based on proper motions and parallaxes. A combined HR diagram shows the same features as observed before using the Hipparcos data, with clearly increased luminosities for older A and F dwarfs.
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| 22. |
- Sung, Yun Ju, et al.
(författare)
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A multi-ancestry genome-wide study incorporating gene-smoking interactions identifies multiple new loci for pulse pressure and mean arterial pressure
- 2019
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Ingår i: Human Molecular Genetics. - : Oxford University Press. - 0964-6906 .- 1460-2083. ; 28:15, s. 2615-2633
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Tidskriftsartikel (refereegranskat)abstract
- Elevated blood pressure (BP), a leading cause of global morbidity and mortality, is influenced by both genetic and lifestyle factors. Cigarette smoking is one such lifestyle factor. Across five ancestries, we performed a genome-wide gene–smoking interaction study of mean arterial pressure (MAP) and pulse pressure (PP) in 129 913 individuals in stage 1 and follow-up analysis in 480 178 additional individuals in stage 2. We report here 136 loci significantly associated with MAP and/or PP. Of these, 61 were previously published through main-effect analysis of BP traits, 37 were recently reported by us for systolic BP and/or diastolic BP through gene–smoking interaction analysis and 38 were newly identified (P < 5 × 10−8, false discovery rate < 0.05). We also identified nine new signals near known loci. Of the 136 loci, 8 showed significant interaction with smoking status. They include CSMD1 previously reported for insulin resistance and BP in the spontaneously hypertensive rats. Many of the 38 new loci show biologic plausibility for a role in BP regulation. SLC26A7 encodes a chloride/bicarbonate exchanger expressed in the renal outer medullary collecting duct. AVPR1A is widely expressed, including in vascular smooth muscle cells, kidney, myocardium and brain. FHAD1 is a long non-coding RNA overexpressed in heart failure. TMEM51 was associated with contractile function in cardiomyocytes. CASP9 plays a central role in cardiomyocyte apoptosis. Identified only in African ancestry were 30 novel loci. Our findings highlight the value of multi-ancestry investigations, particularly in studies of interaction with lifestyle factors, where genomic and lifestyle differences may contribute to novel findings.
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| 23. |
- Shungin, Dmitry, et al.
(författare)
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New genetic loci link adipose and insulin biology to body fat distribution.
- 2015
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 518:7538, s. 187-378
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Tidskriftsartikel (refereegranskat)abstract
- Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms.
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| 24. |
- Joshi, Peter K, et al.
(författare)
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Directional dominance on stature and cognition in diverse human populations
- 2015
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 523:7561, s. 459-462
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Tidskriftsartikel (refereegranskat)abstract
- Homozygosity has long been associated with rare, often devastating, Mendelian disorders, and Darwin was one of the first to recognize that inbreeding reduces evolutionary fitness. However, the effect of the more distant parental relatedness that is common in modern human populations is less well understood. Genomic data now allow us to investigate the effects of homozygosity on traits of public health importance by observing contiguous homozygous segments (runs of homozygosity), which are inferred to be homozygous along their complete length. Given the low levels of genome-wide homozygosity prevalent in most human populations, information is required on very large numbers of people to provide sufficient power. Here we use runs of homozygosity to study 16 health-related quantitative traits in 354,224 individuals from 102 cohorts, and find statistically significant associations between summed runs of homozygosity and four complex traits: height, forced expiratory lung volume in one second, general cognitive ability and educational attainment (P < 1 × 10(-300), 2.1 × 10(-6), 2.5 × 10(-10) and 1.8 × 10(-10), respectively). In each case, increased homozygosity was associated with decreased trait value, equivalent to the offspring of first cousins being 1.2 cm shorter and having 10 months' less education. Similar effect sizes were found across four continental groups and populations with different degrees of genome-wide homozygosity, providing evidence that homozygosity, rather than confounding, directly contributes to phenotypic variance. Contrary to earlier reports in substantially smaller samples, no evidence was seen of an influence of genome-wide homozygosity on blood pressure and low density lipoprotein cholesterol, or ten other cardio-metabolic traits. Since directional dominance is predicted for traits under directional evolutionary selection, this study provides evidence that increased stature and cognitive function have been positively selected in human evolution, whereas many important risk factors for late-onset complex diseases may not have been.
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| 25. |
- Locke, Adam E, et al.
(författare)
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Genetic studies of body mass index yield new insights for obesity biology.
- 2015
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 518:7538, s. 197-401
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Tidskriftsartikel (refereegranskat)abstract
- Obesity is heritable and predisposes to many diseases. To understand the genetic basis of obesity better, here we conduct a genome-wide association study and Metabochip meta-analysis of body mass index (BMI), a measure commonly used to define obesity and assess adiposity, in up to 339,224 individuals. This analysis identifies 97 BMI-associated loci (P < 5 × 10(-8)), 56 of which are novel. Five loci demonstrate clear evidence of several independent association signals, and many loci have significant effects on other metabolic phenotypes. The 97 loci account for ∼2.7% of BMI variation, and genome-wide estimates suggest that common variation accounts for >20% of BMI variation. Pathway analyses provide strong support for a role of the central nervous system in obesity susceptibility and implicate new genes and pathways, including those related to synaptic function, glutamate signalling, insulin secretion/action, energy metabolism, lipid biology and adipogenesis.
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| 30. |
- Haycock, Philip C., et al.
(författare)
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Association Between Telomere Length and Risk of Cancer and Non-Neoplastic Diseases A Mendelian Randomization Study
- 2017
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Ingår i: JAMA Oncology. - : American Medical Association. - 2374-2437 .- 2374-2445. ; 3:5, s. 636-651
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Tidskriftsartikel (refereegranskat)abstract
- IMPORTANCE: The causal direction and magnitude of the association between telomere length and incidence of cancer and non-neoplastic diseases is uncertain owing to the susceptibility of observational studies to confounding and reverse causation. OBJECTIVE: To conduct a Mendelian randomization study, using germline genetic variants as instrumental variables, to appraise the causal relevance of telomere length for risk of cancer and non-neoplastic diseases. DATA SOURCES: Genomewide association studies (GWAS) published up to January 15, 2015. STUDY SELECTION: GWAS of noncommunicable diseases that assayed germline genetic variation and did not select cohort or control participants on the basis of preexisting diseases. Of 163 GWAS of noncommunicable diseases identified, summary data from 103 were available. DATA EXTRACTION AND SYNTHESIS: Summary association statistics for single nucleotide polymorphisms (SNPs) that are strongly associated with telomere length in the general population. MAIN OUTCOMES AND MEASURES: Odds ratios (ORs) and 95% confidence intervals (CIs) for disease per standard deviation (SD) higher telomere length due to germline genetic variation. RESULTS: Summary data were available for 35 cancers and 48 non-neoplastic diseases, corresponding to 420 081 cases (median cases, 2526 per disease) and 1 093 105 controls (median, 6789 per disease). Increased telomere length due to germline genetic variation was generally associated with increased risk for site-specific cancers. The strongest associations (ORs [ 95% CIs] per 1-SD change in genetically increased telomere length) were observed for glioma, 5.27 (3.15-8.81); serous low-malignant-potential ovarian cancer, 4.35 (2.39-7.94); lung adenocarcinoma, 3.19 (2.40-4.22); neuroblastoma, 2.98 (1.92-4.62); bladder cancer, 2.19 (1.32-3.66); melanoma, 1.87 (1.55-2.26); testicular cancer, 1.76 (1.02-3.04); kidney cancer, 1.55 (1.08-2.23); and endometrial cancer, 1.31 (1.07-1.61). Associations were stronger for rarer cancers and at tissue sites with lower rates of stem cell division. There was generally little evidence of association between genetically increased telomere length and risk of psychiatric, autoimmune, inflammatory, diabetic, and other non-neoplastic diseases, except for coronary heart disease (OR, 0.78 [ 95% CI, 0.67-0.90]), abdominal aortic aneurysm (OR, 0.63 [ 95% CI, 0.49-0.81]), celiac disease (OR, 0.42 [ 95% CI, 0.28-0.61]) and interstitial lung disease (OR, 0.09 [ 95% CI, 0.05-0.15]). CONCLUSIONS AND RELEVANCE: It is likely that longer telomeres increase risk for several cancers but reduce risk for some non-neoplastic diseases, including cardiovascular diseases.
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| 31. |
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| 32. |
- Kilpelainen, TO, et al.
(författare)
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Multi-ancestry study of blood lipid levels identifies four loci interacting with physical activity
- 2019
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Ingår i: Nature communications. - London : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 376-
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Tidskriftsartikel (refereegranskat)abstract
- Many genetic loci affect circulating lipid levels, but it remains unknown whether lifestyle factors, such as physical activity, modify these genetic effects. To identify lipid loci interacting with physical activity, we performed genome-wide analyses of circulating HDL cholesterol, LDL cholesterol, and triglyceride levels in up to 120,979 individuals of European, African, Asian, Hispanic, and Brazilian ancestry, with follow-up of suggestive associations in an additional 131,012 individuals. We find four loci, in/near CLASP1, LHX1, SNTA1, and CNTNAP2, that are associated with circulating lipid levels through interaction with physical activity; higher levels of physical activity enhance the HDL cholesterol-increasing effects of the CLASP1, LHX1, and SNTA1 loci and attenuate the LDL cholesterol-increasing effect of the CNTNAP2 locus. The CLASP1, LHX1, and SNTA1 regions harbor genes linked to muscle function and lipid metabolism. Our results elucidate the role of physical activity interactions in the genetic contribution to blood lipid levels.
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| 33. |
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| 34. |
- Combes, F., et al.
(författare)
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ALMA observations of molecular tori around massive black holes
- 2019
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 623
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Tidskriftsartikel (refereegranskat)abstract
- We report Atacama Large Millimeter/submillimeter Array (ALMA) observations of CO(3-2) emission in a sample of seven Seyfert/LINER galaxies at the unprecedented spatial resolution of 0 .″ 1 = 4-8 pc. Our aim is to explore the close environment of active galactic nuclei (AGN), and the dynamical structures leading to their fueling, through the morphology and kinematics of the gas inside the sphere of influence of the black hole. The selected galaxies host low-luminosity AGN and have a wide range of activity types (Seyferts 1 to 2, LINERs), and barred or ringed morphologies. The observed maps reveal the existence of circumnuclear disk structures, defined by their morphology and decoupled kinematics, in most of the sample. We call these structures molecular tori, even though they often appear as disks without holes in the center. They have varying orientations along the line of sight, unaligned with the host galaxy orientation. The radius of the tori ranges from 6 to 27 pc, and their mass from 0.7 × 10 7 to 3.9 × 10 7 M · . The most edge-on orientations of the torus correspond to obscured Seyferts. In only one case (NGC 1365), the AGN is centered on the central gas hole of the torus. On a larger scale, the gas is always piled up in a few resonant rings 100 pc in scale that play the role of a reservoir to fuel the nucleus. In some cases, a trailing spiral is observed inside the ring, providing evidence for feeding processes. More frequently, the torus and the AGN are slightly off-centered with respect to the bar-resonant ring position, implying that the black hole is wandering by a few 10 pc amplitude around the center of mass of the galaxy. Our spatial resolution allows us to measure gas velocities inside the sphere of influence of the central black holes. By fitting the observations with different simulated cubes, varying the torus inclination and the black hole mass, it is possible to estimate the mass of the central black hole, which is in general difficult for such late-type galaxies, with only a pseudo-bulge. In some cases, AGN feedback is revealed through a molecular outflow, which will be studied in detail in a subsequent article.
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| 35. |
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| 36. |
- Galli, L., et al.
(författare)
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Electronic damage in S atoms in a native protein crystal induced by an intense X-ray free-electron laser pulse
- 2015
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Ingår i: Structural Dynamics. - : AIP Publishing. - 2329-7778. ; 2:4
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Tidskriftsartikel (refereegranskat)abstract
- Current hard X-ray free-electron laser (XFEL) sources can deliver doses to biological macromolecules well exceeding 1 GGy, in timescales of a few tens of femtoseconds. During the pulse, photoionization can reach the point of saturation in which certain atomic species in the sample lose most of their electrons. This electronic radiation damage causes the atomic scattering factors to change, affecting, in particular, the heavy atoms, due to their higher photoabsorption cross sections. Here, it is shown that experimental serial femtosecond crystallography data collected with an extremely bright XFEL source exhibit a reduction of the effective scattering power of the sulfur atoms in a native protein. Quantitative methods are developed to retrieve information on the effective ionization of the damaged atomic species from experimental data, and the implications of utilizing new phasing methods which can take advantage of this localized radiation damage are discussed.
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| 37. |
- Audibert, A., et al.
(författare)
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ALMA captures feeding and feedback from the active galactic nucleus in NGC 613
- 2019
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 632
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Tidskriftsartikel (refereegranskat)abstract
- We report ALMA observations of CO(3-2) emission in the Seyfert/nuclear starburst galaxy NGC 613, at a spatial resolution of 17 pc, as part of our NUclei of GAlaxies (NUGA) sample. Our aim is to investigate the morphology and dynamics of the gas inside the central kiloparsec, and to probe nuclear fueling and feedback phenomena. The morphology of CO(3-2) line emission reveals a two-arm trailing nuclear spiral at r≤ 100 pc and a circumnuclear ring at a radius of ∼350 pc that is coincident with the star-forming ring seen in the optical images. Also, we find evidence for a filamentary structure connecting the ring and the nuclear spiral. The ring reveals two breaks into two winding spiral arms corresponding to the dust lanes in the optical images. The molecular gas in the galaxy disk is in a remarkably regular rotation, however the kinematics in the nuclear region are very skewed. The nuclear spectrum of CO and dense gas tracers HCN(4-3), HCO+(4-3), and CS(7-6) show broad wings up to ±300 km s-1, associated with a molecular outflow emanating from the nucleus (r ∼ 25 pc). We derive a molecular outflow mass Mout=2 × 106 M⊙ and a mass outflow rate of M out = 27 M⊙ yr-1. The molecular outflow energetics exceed the values predicted by AGN feedback models: the kinetic power of the outflow corresponds to PK, out=20%LAGN and the momentum rate is M outv ∼400LAGN/c. The outflow is mainly boosted by the AGN through entrainment by the radio jet, but given the weak nuclear activity of NGC 613, we might be witnessing a fossil outflow resulting from a previously strong AGN that has now faded. Furthermore, the nuclear trailing spiral observed in CO emission is inside the inner Lindblad resonance ring of the bar. We compute the gravitational torques exerted in the gas to estimate the efficiency of the angular momentum exchange. The gravity torques are negative from 25 to 100 pc and the gas loses its angular momentum in a rotation period, providing evidence for a highly efficient inflow towards the center. This phenomenon shows that the massive central black hole has significant dynamical influence on the gas, triggering the inflowing of molecular gas to feed the black hole.
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| 38. |
- Bell, D., et al.
(författare)
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Neuroendocrine neoplasms of the sinonasal region
- 2016
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Ingår i: Head and Neck-Journal for the Sciences and Specialties of the Head and Neck. - : Wiley. - 1043-3074. ; 38:S1
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Tidskriftsartikel (refereegranskat)abstract
- Neuroendocrine neoplasms of the sinonasal region, which are relatively uncommon but clinically very important, are reviewed here in the light of current knowledge. Using a definition for neuroendocrine based on phenotypic, histologic, immunohistochemical, and electron microscopic features rather than histogenetic criteria, sinonasal neuroendocrine carcinomas are examined with a particular emphasis on the small-cell and large-cell subtypes. This is followed by revisiting olfactory neuroblastoma because it is also a tumor that shows a neuroendocrine phenotype. Kadish clinical and Hyams histologic grading systems as prognosticators of olfactory neuroblastoma are also considered in detail. Finally, controversies regarding sinonasal undifferentiated carcinoma as a neuroendocrine tumor are discussed and a possible relationship with high-grade olfactory neuroblastoma is explored. Genetic events and current management of these tumors are also outlined.
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| 39. |
- Goodwin, G. M., et al.
(författare)
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Evidence-based guidelines for treating bipolar disorder : Revised third edition recommendations from the British Association for Psychopharmacology
- 2016
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Ingår i: Journal of Psychopharmacology. - : SAGE PUBLICATIONS LTD. - 0269-8811 .- 1461-7285. ; 30:6, s. 495-553
-
Forskningsöversikt (refereegranskat)abstract
- The British Association for Psychopharmacology guidelines specify the scope and targets of treatment for bipolar disorder. The third version is based explicitly on the available evidence and presented, like previous Clinical Practice Guidelines, as recommendations to aid clinical decision making for practitioners: it may also serve as a source of information for patients and carers, and assist audit. The recommendations are presented together with a more detailed review of the corresponding evidence. A consensus meeting, involving experts in bipolar disorder and its treatment, reviewed key areas and considered the strength of evidence and clinical implications. The guidelines were drawn up after extensive feedback from these participants. The best evidence from randomized controlled trials and, where available, observational studies employing quasi-experimental designs was used to evaluate treatment options. The strength of recommendations has been described using the GRADE approach. The guidelines cover the diagnosis of bipolar disorder, clinical management, and strategies for the use of medicines in short-term treatment of episodes, relapse prevention and stopping treatment. The use of medication is integrated with a coherent approach to psychoeducation and behaviour change.
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| 40. |
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| 41. |
- Henkel, C., et al.
(författare)
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Molecular line emission in NGC 4945, imaged with ALMA
- 2018
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 615
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Tidskriftsartikel (refereegranskat)abstract
- NGC 4945 is one of the nearest (D ≈ 3.8 Mpc; 1 00 ≈ 19 pc) starburst galaxies. To investigate the structure, dynamics, and composition of the dense nuclear gas of this galaxy, ALMA band 3 (λ ≈ 3−4 mm) observations were carried out with ≈2 00 resolution. Three HCN and two HC + isotopologues, CS, C 3 H 2 , SiO, HCO, and CH 3 C 2 H were measured. Spectral line imaging demonstrates the presence of a rotating nuclear disk of projected size 10 00 × 2 00 reaching out to a galactocentric radius of r ≈ 100 pc with position angle PA = 45 ◦ ± 2 ◦ , inclination i = 75 ◦ ± 2 ◦ and an unresolved bright central core of size <∼ 2 00 . The continuum source, representing mostly free-free radiation from star forming regions, is more compact than the nuclear disk by a linear factor of two but shows the same position angle and is centered 0 00 . 39 ± 0 00 . 14 northeast of the nuclear accretion disk defined by H 2 O maser emission. Near the systemic velocity but outside the nuclear disk, both HCN J = 1 → 0 and CS J = 2 → 1 delineate molecular arms of length >∼ 15 00 ( >∼ 285 pc) on opposite sides of the dynamical center. These are connected by a (deprojected) ≈ 0.6 kpc sized molecular bridge, likely a dense gaseous bar seen almost ends-on, shifting gas from the front and back side into the nuclear disk. Modeling this nuclear disk located farther inside (r <∼ 100 pc) with tilted rings provides a good fit by inferring a coplanar outflow reaching a characteristic deprojected velocity of ≈50 km s −1 . All our molecular lines, with the notable exception of CH 3 C 2 H, show significant absorption near the systemic velocity (≈571 km s −1 ), within the range ≈500-660 km s −1 . Apparently, only molecular transitions with low critical H 2 density (n crit<∼ 10 4 cm −3 ) do not show absorption. The velocity field of the nuclear disk, derived from CH 3 C 2 H, provides evidence for rigid rotation in the inner few arcseconds and a dynamical mass of M tot = (2.1 ± 0.2) × 10 8 M inside a galactocentric radius of 2 00 . 45 (≈45 pc), with a significantly flattened rotation curve farther out. Velocity integrated line intensity maps with most pronounced absorption show molecular peak positions up to ≈1 00 . 5 (≈30 pc) southwest of the continuum peak, presumably due to absorption, which appears to be most severe slightly northeast of the nuclear maser disk. A nitrogen isotope ratio of 14 N/ 15 N ≈ 200-450 is estimated. This range of values is much higher then previously reported on a tentative basis. Therefore, because 15 N is less abundant than expected, the question for strong 15 N enrichment by massive star ejecta in starbursts still remains to be settled.
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| 42. |
- Michels, F., et al.
(författare)
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Searching for consensus in the approach to patients with chronic lateral ankle instability: ask the expert
- 2018
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Ingår i: Knee Surgery Sports Traumatology Arthroscopy. - : Springer Science and Business Media LLC. - 0942-2056 .- 1433-7347. ; 26:7, s. 2095-2102
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Tidskriftsartikel (refereegranskat)abstract
- The purpose of this study is to propose recommendations for the treatment of patients with chronic lateral ankle instability (CAI) based on expert opinions. A questionnaire was sent to 32 orthopaedic surgeons with clinical and scientific experience in the treatment of CAI. The questions were related to preoperative imaging, indications and timing of surgery, technical choices, and the influence of patient-related aspects. Thirty of the 32 invited surgeons (94%) responded. Consensus was found on several aspects of treatment. Preoperative MRI was routinely recommended. Surgery was considered in patients with functional ankle instability after 3-6 months of non-surgical treatment. Ligament repair is still the treatment of choice in patients with mechanical instability; however, in patients with generalized laxity or poor ligament quality, lateral ligament reconstruction (with grafting) of both the ATFL and CFL should be considered. Most surgeons request an MRI during the preoperative planning. There is a trend towards earlier surgical treatment (after failure of non-surgical treatment) in patients with mechanical ligament laxity (compared with functional instability) and in high-level athletes. This study proposes an assessment and a treatment algorithm that may be used as a recommendation in the treatment of patients with CAI.
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| 43. |
- Skalova, A., et al.
(författare)
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The Role of Molecular Testing in the Differential Diagnosis of Salivary Gland Carcinomas
- 2018
-
Ingår i: American Journal of Surgical Pathology. - : Ovid Technologies (Wolters Kluwer Health). - 0147-5185 .- 1532-0979. ; 42:2
-
Tidskriftsartikel (refereegranskat)abstract
- Salivary gland neoplasms are a morphologically heterogenous group of lesions that are often diagnostically challenging. In recent years, considerable progress in salivary gland taxonomy has been reached by the discovery of tumor type-specific fusion oncogenes generated by chromosome translocations. This review describes the clinicopathologic features of a selected group of salivary gland carcinomas with a focus on their distinctive genomic characteristics. Mammary analog secretory carcinoma is a recently described entity characterized by a t(12;15)(p13;q25) translocation resulting in an ETV6-NTRK3 fusion. Hyalinizing clear cell carcinoma is a low-grade tumor with infrequent nodal and distant metastasis, recently shown to harbor an EWSR1-ATF1 gene fusion. The CRTC1-MAML2 fusion gene resulting from a t(11;19)(q21;p13) translocation, is now known to be a feature of both low-grade and high-grade mucoepidermoid carcinomas associated with improved survival. A t(6;9)(q22-23;p23-34) translocation resulting in a MYB-NFIB gene fusion has been identified in the majority of adenoid cystic carcinomas. Polymorphous (low-grade) adenocarcinoma and cribriform adenocarcinoma of (minor) salivary gland origin are related entities with partly differing clinicopathologic and genomic profiles; they are the subject of an ongoing taxonomic debate. Polymorphous (low-grade) adenocarcinomas are characterized by hot spot point E710D mutations in the PRKD1 gene, whereas cribriform adenocarcinoma of (minor) salivary glands origin are characterized by translocations involving the PRKD1-3 genes. Salivary duct carcinoma (SDC) is a high-grade adenocarcinoma with morphologic and molecular features akin to invasive ductal carcinoma of the breast, including HER2 gene amplification, mutations of TP53, PIK3CA, and HRAS and loss or mutation of PTEN. Notably, a recurrent NCOA4-RET fusion has also been found in SDC. A subset of SDC with apocrine morphology is associated with overexpression of androgen receptors. As these genetic aberrations are recurrent they serve as powerful diagnostic tools in salivary gland tumor diagnosis, and therefore also in refinement of salivary gland cancer classification. Moreover, they are promising as prognostic biomarkers and targets of therapy.
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| 44. |
- Aguado, D. S., et al.
(författare)
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The Fifteenth Data Release of the Sloan Digital Sky Surveys : First Release of MaNGA-derived Quantities, Data Visualization Tools, and Stellar Library
- 2019
-
Ingår i: Astrophysical Journal Supplement Series. - : Institute of Physics Publishing (IOPP). - 0067-0049 .- 1538-4365. ; 240:2
-
Tidskriftsartikel (refereegranskat)abstract
- Twenty years have passed since first light for the Sloan Digital Sky Survey (SDSS). Here, we release data taken by the fourth phase of SDSS (SDSS-IV) across its first three years of operation (2014 July-2017 July). This is the third data release for SDSS-IV, and the 15th from SDSS (Data Release Fifteen; DR15). New data come from MaNGA-we release 4824 data cubes, as well as the first stellar spectra in the MaNGA Stellar Library (MaStar), the first set of survey-supported analysis products (e.g., stellar and gas kinematics, emission-line and other maps) from the MaNGA Data Analysis Pipeline, and a new data visualization and access tool we call "Marvin." The next data release, DR16, will include new data from both APOGEE-2 and eBOSS; those surveys release no new data here, but we document updates and corrections to their data processing pipelines. The release is cumulative; it also includes the most recent reductions and calibrations of all data taken by SDSS since first light. In this paper, we describe the location and format of the data and tools and cite technical references describing how it was obtained and processed. The SDSS website (www.sdss.org) has also been updated, providing links to data downloads, tutorials, and examples of data use. Although SDSS-IV will continue to collect astronomical data until 2020, and will be followed by SDSS-V (2020-2025), we end this paper by describing plans to ensure the sustainability of the SDSS data archive for many years beyond the collection of data.
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| 45. |
- Akca, Ozan, et al.
(författare)
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WHO Needs High FIO2?
- 2017
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Ingår i: TURKISH JOURNAL OF ANAESTHESIOLOGY AND REANIMATION. - : AVES. - 2149-0937. ; 45:4, s. 181-192
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Tidskriftsartikel (refereegranskat)abstract
- World Health Organization and the United States Center for Disease Control have recently recommended the use of 0.8 FIO2 in all adult surgical patients undergoing general anaesthesia, to prevent surgical site infections. This recommendation has arisen several discussions: As a matter of fact, there are numerous studies with different results about the effect of FIO2 on surgical site infection. Moreover, the clinical effects of FIO2 are not limited to infection control. We asked some prominent authors about their comments regarding the recent recommendations
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| 46. |
- Bishop, J. A., et al.
(författare)
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Rhabdomyoblastic Differentiation in Head and Neck Malignancies Other Than Rhabdomyosarcoma
- 2015
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Ingår i: Head and Neck Pathology. - : Springer Science and Business Media LLC. - 1936-055X .- 1936-0568. ; 9:4, s. 507-518
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Tidskriftsartikel (refereegranskat)abstract
- Rhabdomyosarcoma is a relatively common soft tissue sarcoma that frequently affects children and adolescents and may involve the head and neck. Rhabdomyosarcoma is defined by skeletal muscle differentiation which can be suggested by routine histology and confirmed by immunohistochemistry for the skeletal muscle-specific markers myogenin or myoD1. At the same time, it must be remembered that when it comes to head and neck malignancies, skeletal muscle differentiation is not limited to rhabdomyosarcoma. A lack of awareness of this phenomenon could lead to misdiagnosis and, subsequently, inappropriate therapeutic interventions. This review focuses on malignant neoplasms of the head and neck other than rhabdomyosarcoma that may exhibit rhabdomyoblastic differentiation, with an emphasis on strategies to resolve the diagnostic dilemmas these tumors may present. Axiomatically, no primary central nervous system tumors will be discussed. © 2015, Springer Science+Business Media New York.
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| 47. |
- Burillo, S. G., et al.
(författare)
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ALMA images the many faces of the NGC 1068 torus and its surroundings
- 2019
-
Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 632
-
Tidskriftsartikel (refereegranskat)abstract
- Aims. We investigate the fueling and the feedback of nuclear activity in the nearby (D = 14 Mpc) Seyfert 2 barred galaxy NGC 1068 by studying the distribution and kinematics of molecular gas in the torus and its connections to the host galaxy disk. Methods.We used the Atacama Large Millimeter Array (ALMA ) to image the emission of a set of molecular gas tracers in the circumnuclear disk (CND) and the torus of the galaxy using the CO(2-1), CO(3-2), and HCO+(4-3) lines and their underlying continuum emission with high spatial resolutions (0:0300 0:0900 ' 26 pc). These transitions, which span a wide range of physical conditions of molecular gas (n(H2) 103107 cm3), are instrumental in revealing the density radial stratification and the complex kinematics of the gas in the torus and its surroundings. Results. The ALMA images resolve the CND as an asymmetric ringed disk of D ' 400 pc in size and '1:4 108 M in mass. The CND shows a marked deficit of molecular gas in its central '130 pc region. The inner edge of the ring is associated with the presence of edge-brightened arcs of NIR polarized emission, which are identified with the current working surface of the ionized wind of the active galactic nucleus (AGN). ALMA proves the existence of an elongated molecular disk/torus in NGC 1068 of Mgas torus ' 3 105 M, which extends over a large range of spatial scales D ' 1030 pc around the central engine. The new observations evidence the density radial stratification of the torus: the HCO+(4-3) torus, with a full size DHCO+(43) = 11 0:6 pc, is a factor of between two and three smaller than its CO(2-1) and CO(3-2) counterparts, which have full sizes of DCO(32) = 26 0:6 pc and DCO(21) = 28 0:6 pc, respectively. This result brings into light the many faces of the molecular torus. The torus is connected to the CND through a network of molecular gas streamers detected inside the CND ring. The kinematics of molecular gas show strong departures from circular motions in the torus, the gas streamers, and the CND ring. These velocity field distortions are interconnected and are part of a 3D outflow that reflects the eects of AGN feedback on the kinematics of molecular gas across a wide range of spatial scales around the central engine. In particular, we estimate through modeling that a significant fraction of the gas inside the torus ('0:40:6 Mgas torus) and a comparable amount of mass along the gas streamers are outflowing. However, the bulk of the mass, momentum, and energy of the molecular outflow of NGC 1068 is contained at larger radii in the CND region, where the AGN wind and the radio jet are currently pushing the gas assembled at the Inner Lindblad Resonance (ILR) ring of the nuclear stellar bar. Conclusions. In our favored scenario a wide-angle AGN wind launched from the accretion disk of NGC1068 is currently impacting a sizable fraction of the gas inside the torus. However, a large gas reservoir ('1:21:8 105 M), which lies close to the equatorial plane of the torus, remains unaected by the feedback of the AGN wind and can therefore continue fueling the AGN for at least '14 Myr. Nevertheless, AGN fueling currently seems thwarted on intermediate scales (15 pc r 50 pc).
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| 48. |
- Burillo, S. G., et al.
(författare)
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ALMA imaging of C2H emission in the disk of NGC 1068
- 2017
-
Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 608, s. A56-
-
Tidskriftsartikel (refereegranskat)abstract
- Aims. We study the feedback of star formation and nuclear activity on the chemistry of molecular gas in NGC 1068, a nearby (D = 14 Mpc) Seyfert 2 barred galaxy, by analyzing whether the abundances of key molecular species such as ethynyl (C2H), which is a classical tracer of photon dominated regions (PDR), change in the different environments of the disk of the galaxy. Methods. We used the Atacama Large Millimeter Array (ALMA) to map the emission of the hyperfine multiplet of C2H(N = 1-0) and its underlying continuum emission in the central r similar or equal to 35" (2.5 kpc) region of the disk of NGC 1068 with a spatial resolution 1.0 x 0.7 (similar or equal to 50-70 pc). We used maps of the dust continuum emission obtained at 349 GHz by ALMA to derive the H-2 gas column densities and combined these with the C2H map at matched spatial resolution to estimate the fractional abundance of this species. We developed a set of time-dependent chemical models, which include shocks, gas-phase PDRs, and gas-grain chemical models to determine the origin of the C2H gas. Results. A sizeable fraction of the total C2H line emission is detected from the r similar or equal to 1.3 kpc starburst (SB) ring, which is a region that concentrates the bulk of the recent massive star formation in the disk traced by the Pa alpha emission complexes imaged by the Hubble Space Telescope (HST). However, the brightest C2H emission originates from a r similar or equal to 200 pc off -centered circumnuclear disk (CND), where evidence of a molecular outflow has been previously found in other molecular tracers imaged by ALMA. We also detect significant emission that connects the CND with the outer disk in a region that probes the interface between the molecular disk and ionized gas outflow out to r similar or equal to 400 pc. We derived the fractional abundances of C2H (X(C2H)) assuming local thermodynamic equilibrium (LTE) conditions and a set of excitation temperatures (T-ex) constrained by the previous multiline CO studies of the galaxy. Our estimates range from X(C2H) similar or equal to a few 10(-8) in the SB ring up to X(C2H) similar or equal to a few 10(-7) in the outflow region. The PDR models that incorporate gas-grain chemistry are able to account for X(C2H) in the SB ring for moderately dense (n(H-2) >= 10(4) cm(-3)) and moderately UV-irradiated gas (UV-field = 10(4-5) cm(-3)). Conclusions. We find that the transient conditions required to fit the high values of X(C2H) in the outflow are likely due to UV or X-ray irradiated non-dissociative shocks associated with the highly turbulent interface between the outflow and molecular gas in NGC 1068. Although the inferred local timescales are short, the erosion of molecular clouds by the active galactic nucleus (AGN) wind and/or the jet likely resupplies the interface working surface continuously, making a nearly steady state persist in the disk of the galaxy.
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| 49. |
- Burillo, S. G., et al.
(författare)
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ALMA resolves the torus of NGC 1068: Continuum and molecular line emission
- 2016
-
Ingår i: Astrophysical Journal Letters. - : American Astronomical Society. - 2041-8213 .- 2041-8205. ; 823:1, s. Art. no. L12-
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Tidskriftsartikel (refereegranskat)abstract
- We used the Atacama Large Millimeter Array (ALMA) to map the emission of the CO(6-5) molecular line and the 432 mu m continuum emission from the 300 pc sized circumnuclear disk (CND) of the nearby Seyfert 2 galaxy NGC 1068 with a spatial resolution of similar to 4 pc. These observations spatially resolve the CND and, for the first time, image the dust emission, the molecular gas distribution, and the kinematics from a 7-10 pc diameter disk that represents the submillimeter counterpart of the putative torus of NGC 1068. We fitted the nuclear spectral energy distribution of the torus using ALMA and near-and mid-infrared (NIR/MIR) data with CLUMPY torus models. The mass and radius of the best-fit solution for the torus are both consistent with the values derived from the ALMA data alone: M-gas(torus) = (1 +/- 0.3) x 10(5) M-circle dot and R-torus = 3.5 +/- 0.5 pc. The dynamics of the molecular gas in the torus show strong non-circular motions and enhanced turbulence superposed on a surprisingly slow rotation pattern of the disk. By contrast with the nearly edge-on orientation of the H2O megamaser disk, we found evidence suggesting that the molecular torus is less inclined (i = 34 degrees-66 degrees) at larger radii. The lopsided morphology and complex kinematics of the torus could be the signature of the Papaloizou-Pringle instability, long predicted to likely drive the dynamical evolution of active galactic nuclei tori.
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| 50. |
- Burillo, S. G., et al.
(författare)
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High-resolution imaging of the molecular outflows in two mergers: IRAS 17208-0014 and NGC 1614
- 2015
-
Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 580
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Tidskriftsartikel (refereegranskat)abstract
- Context. Galaxy evolution scenarios predict that the feedback of star formation and nuclear activity (AGN) can drive the transformation of gas-rich spiral mergers into (ultra) luminous infrared galaxies and, eventually, lead to the build-up of QSO/elliptical hosts. Aims. We study the role that star formation and AGN feedback have in launching and maintaining the molecular outflows in two starburst-dominated advanced mergers, NGC 1614 (DL = 66 Mpc) and IRAS 17208-0014 (DL = 181 Mpc), by analyzing the distribution and kinematics of their molecular gas reservoirs. Both galaxies present evidence of outflows in other phases of their ISM. Methods. We used the Plateau de Bure interferometer (PdBI) to image the CO(10) and CO(21) line emissions in NGC 1614 and IRAS 17208-0014, respectively, with high spatial resolution (0: 0051: 002). The velocity fields of the gas were analyzed and modeled to find the evidence of molecular outflows in these sources and characterize the mass, momentum, and energy of these components. Results. While most (95%) of the CO emission stems from spatially resolved (23 kpc-diameter) rotating disks, we also detect in both mergers the emission from high-velocity line wings that extend up to -500-700 km s1, well beyond the estimated virial range associated with rotation and turbulence. The kinematic major axis of the line-wing emission is tilted by 90 in NGC 1614 and by 180 in IRAS 17208-0014 relative to the major axes of their respective rotating disks. These results can be explained by the existence of non-coplanar molecular outflows in both systems: the outflow axis is nearly perpendicular to the rotating disk in NGC 1614, but it is tilted relative to the angular momentum axis of the rotating disk in IRAS 17208-0014. Conclusions. In stark contrast to NGC 1614, where star formation alone can drive its molecular outflow, the mass, energy, and momentum budget requirements of the molecular outflow in IRAS 17208-0014 can be best accounted for by the existence of a so far undetected (hidden) AGN of LAGN71011 L The geometry of the molecular outflow in IRAS 17208-0014 suggests that the outflow is launched by a non-coplanar disk that may be associated with a buried AGN in the western nucleus.
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