| 1. |
- Weinstein, John N., et al.
(författare)
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The cancer genome atlas pan-cancer analysis project
- 2013
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 45:10, s. 1113-1120
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Forskningsöversikt (refereegranskat)abstract
- The Cancer Genome Atlas (TCGA) Research Network has profiled and analyzed large numbers of human tumors to discover molecular aberrations at the DNA, RNA, protein and epigenetic levels. The resulting rich data provide a major opportunity to develop an integrated picture of commonalities, differences and emergent themes across tumor lineages. The Pan-Cancer initiative compares the first 12 tumor types profiled by TCGA. Analysis of the molecular aberrations and their functional roles across tumor types will teach us how to extend therapies effective in one cancer type to others with a similar genomic profile. © 2013 Nature America, Inc. All rights reserved.
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| 2. |
- Hudson, Thomas J., et al.
(författare)
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International network of cancer genome projects
- 2010
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 464:7291, s. 993-998
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Tidskriftsartikel (refereegranskat)abstract
- The International Cancer Genome Consortium (ICGC) was launched to coordinate large-scale cancer genome studies in tumours from 50 different cancer types and/or subtypes that are of clinical and societal importance across the globe. Systematic studies of more than 25,000 cancer genomes at the genomic, epigenomic and transcriptomic levels will reveal the repertoire of oncogenic mutations, uncover traces of the mutagenic influences, define clinically relevant subtypes for prognosis and therapeutic management, and enable the development of new cancer therapies.
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| 3. |
- Ferrari, Raffaele, et al.
(författare)
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Frontotemporal dementia and its subtypes: a genome-wide association study.
- 2014
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Ingår i: Lancet Neurology. - 1474-4465. ; 13:7, s. 686-699
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Tidskriftsartikel (refereegranskat)abstract
- Frontotemporal dementia (FTD) is a complex disorder characterised by a broad range of clinical manifestations, differential pathological signatures, and genetic variability. Mutations in three genes-MAPT, GRN, and C9orf72-have been associated with FTD. We sought to identify novel genetic risk loci associated with the disorder.
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| 4. |
- Wang, Haidong, et al.
(författare)
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Global, regional, and national levels of neonatal, infant, and under-5 mortality during 1990-2013 : a systematic analysis for the Global Burden of Disease Study 2013
- 2014
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Ingår i: The Lancet. - 0140-6736 .- 1474-547X. ; 384:9947, s. 957-979
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Remarkable financial and political efforts have been focused on the reduction of child mortality during the past few decades. Timely measurements of levels and trends in under-5 mortality are important to assess progress towards the Millennium Development Goal 4 (MDG 4) target of reduction of child mortality by two thirds from 1990 to 2015, and to identify models of success.METHODS: We generated updated estimates of child mortality in early neonatal (age 0-6 days), late neonatal (7-28 days), postneonatal (29-364 days), childhood (1-4 years), and under-5 (0-4 years) age groups for 188 countries from 1970 to 2013, with more than 29 000 survey, census, vital registration, and sample registration datapoints. We used Gaussian process regression with adjustments for bias and non-sampling error to synthesise the data for under-5 mortality for each country, and a separate model to estimate mortality for more detailed age groups. We used explanatory mixed effects regression models to assess the association between under-5 mortality and income per person, maternal education, HIV child death rates, secular shifts, and other factors. To quantify the contribution of these different factors and birth numbers to the change in numbers of deaths in under-5 age groups from 1990 to 2013, we used Shapley decomposition. We used estimated rates of change between 2000 and 2013 to construct under-5 mortality rate scenarios out to 2030.FINDINGS: We estimated that 6·3 million (95% UI 6·0-6·6) children under-5 died in 2013, a 64% reduction from 17·6 million (17·1-18·1) in 1970. In 2013, child mortality rates ranged from 152·5 per 1000 livebirths (130·6-177·4) in Guinea-Bissau to 2·3 (1·8-2·9) per 1000 in Singapore. The annualised rates of change from 1990 to 2013 ranged from -6·8% to 0·1%. 99 of 188 countries, including 43 of 48 countries in sub-Saharan Africa, had faster decreases in child mortality during 2000-13 than during 1990-2000. In 2013, neonatal deaths accounted for 41·6% of under-5 deaths compared with 37·4% in 1990. Compared with 1990, in 2013, rising numbers of births, especially in sub-Saharan Africa, led to 1·4 million more child deaths, and rising income per person and maternal education led to 0·9 million and 2·2 million fewer deaths, respectively. Changes in secular trends led to 4·2 million fewer deaths. Unexplained factors accounted for only -1% of the change in child deaths. In 30 developing countries, decreases since 2000 have been faster than predicted attributable to income, education, and secular shift alone.INTERPRETATION: Only 27 developing countries are expected to achieve MDG 4. Decreases since 2000 in under-5 mortality rates are accelerating in many developing countries, especially in sub-Saharan Africa. The Millennium Declaration and increased development assistance for health might have been a factor in faster decreases in some developing countries. Without further accelerated progress, many countries in west and central Africa will still have high levels of under-5 mortality in 2030.
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| 5. |
- Tinetti, Giovanna, et al.
(författare)
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The science of EChO
- 2010
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Ingår i: Proceedings of the International Astronomical Union. - 1743-9213 .- 1743-9221. ; 6:S276, s. 359-370
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Tidskriftsartikel (refereegranskat)abstract
- The science of extra-solar planets is one of the most rapidly changing areas of astrophysics and since 1995 the number of planets known has increased by almost two orders of magnitude. A combination of ground-based surveys and dedicated space missions has resulted in 560-plus planets being detected, and over 1200 that await confirmation. NASA's Kepler mission has opened up the possibility of discovering Earth-like planets in the habitable zone around some of the 100,000 stars it is surveying during its 3 to 4-year lifetime. The new ESA's Gaia mission is expected to discover thousands of new planets around stars within 200 parsecs of the Sun. The key challenge now is moving on from discovery, important though that remains, to characterisation: what are these planets actually like, and why are they as they are In the past ten years, we have learned how to obtain the first spectra of exoplanets using transit transmission and emission spectroscopy. With the high stability of Spitzer, Hubble, and large ground-based telescopes the spectra of bright close-in massive planets can be obtained and species like water vapour, methane, carbon monoxide and dioxide have been detected. With transit science came the first tangible remote sensing of these planetary bodies and so one can start to extrapolate from what has been learnt from Solar System probes to what one might plan to learn about their faraway siblings. As we learn more about the atmospheres, surfaces and near-surfaces of these remote bodies, we will begin to build up a clearer picture of their construction, history and suitability for life. The Exoplanet Characterisation Observatory, EChO, will be the first dedicated mission to investigate the physics and chemistry of Exoplanetary Atmospheres. By characterising spectroscopically more bodies in different environments we will take detailed planetology out of the Solar System and into the Galaxy as a whole. EChO has now been selected by the European Space Agency to be assessed as one of four M3 mission candidates. © International Astronomical Union 2011.
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| 6. |
- Mills, Nicholas L., et al.
(författare)
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Combustion-derived nanoparticulate induces the adverse vascular effects of diesel exhaust inhalation
- 2011
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Ingår i: European Heart Journal. - London : Academic Press. - 0195-668X .- 1522-9645. ; 32:21, s. 2660-2671
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Tidskriftsartikel (refereegranskat)abstract
- Aim: Exposure to road traffic and air pollution may be a trigger of acute myocardial infarction, but the individual pollutants responsible for this effect have not been established. We assess the role of combustion-derived-nanoparticles in mediating the adverse cardiovascular effects of air pollution. Methods and results: To determine the in vivo effects of inhalation of diesel exhaust components, 16 healthy volunteers were exposed to (i) dilute diesel exhaust, (ii) pure carbon nanoparticulate, (iii) filtered diesel exhaust, or (iv) filtered air, in a randomized double blind cross-over study. Following each exposure, forearm blood flow was measured during intra-brachial bradykinin, acetylcholine, sodium nitroprusside, and verapamil infusions. Compared with filtered air, inhalation of diesel exhaust increased systolic blood pressure (145 +/- 4 vs. 133 +/- 3 mmHg, P < 0.05) and attenuated vasodilatation to bradykinin (P = 0.005), acetylcholine (P = 0.008), and sodium nitroprusside (P < 0.001). Exposure to pure carbon nanoparticulate or filtered exhaust had no effect on endothelium-dependent or -independent vasodilatation. To determine the direct vascular effects of nanoparticulate, isolated rat aortic rings (n = 6-9 per group) were assessed in vitro by wire myography and exposed to diesel exhaust particulate, pure carbon nanoparticulate and vehicle. Compared with vehicle, diesel exhaust particulate (but not pure carbon nanoparticulate) attenuated both acetylcholine (P < 0.001) and sodium-nitroprusside (P = 0.019)-induced vasorelaxation. These effects were partially attributable to both soluble and insoluble components of the particulate. Conclusion: Combustion-derived nanoparticulate appears to predominately mediate the adverse vascular effects of diesel exhaust inhalation. This provides a rationale for testing environmental health interventions targeted at reducing traffic-derived particulate emissions.
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| 7. |
- Viana, Pedro T. P., et al.
(författare)
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The XMM Cluster Survey : predicted overlap with the Planck Cluster Catalogue
- 2012
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Ingår i: Monthly notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 422:2, s. 1007-1013
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Tidskriftsartikel (refereegranskat)abstract
- We present a list of 15 clusters of galaxies, serendipitously detected by the XMM Cluster Survey (XCS), that have a high probability of detection by the Planck satellite. Three of them already appear in the Planck Early Sunyaev-Zel'dovich (ESZ) catalogue. The estimation of the Planck detection probability assumes the flat Lambda cold dark matter (Lambda CDM) cosmology most compatible with 7-year Wilkinson Microwave Anisotropy Probe (WMAP7) data. It takes into account the XCS selection function and Planck sensitivity, as well as the covariance of the cluster X-ray luminosity, temperature and integrated Comptonization parameter, as a function of cluster mass and redshift, determined by the Millennium gas simulations. We also characterize the properties of the galaxy clusters in the final data release of the XCS that we expect Planck will have detected by the end of its extended mission. Finally, we briefly discuss possible joint applications of the XCS and Planck data.
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| 8. |
- Hilton, Matt, et al.
(författare)
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The XMM Cluster Survey : evidence for energy injection at high redshift from evolution of the X-ray luminosity-temperature relation
- 2012
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Ingår i: Monthly notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 424:3, s. 2086-2096
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Tidskriftsartikel (refereegranskat)abstract
- We measure the evolution of the X-ray luminositytemperature (LX - T) relation since z similar to 1.5 using a sample of 211 serendipitously detected galaxy clusters with spectroscopic redshifts drawn from the XMM Cluster Survey first data release (XCS-DR1). This is the first study spanning this redshift range using a single, large, homogeneous cluster sample. Using an orthogonal regression technique, we find no evidence for evolution in the slope or intrinsic scatter of the relation since z similar to 1.5, finding both to be consistent with previous measurements at z similar to 0.1. However, the normalization is seen to evolve negatively with respect to the self-similar expectation: we find E-1(z)?LX = 1044.67 +/- 0.09(T/5)3.04 +/- 0.16(1 + z)-1.5 +/- 0.5, which is within 2 sigma of the zero evolution case. We see milder, but still negative, evolution with respect to self-similar when using a bisector regression technique. We compare our results to numerical simulations, where we fit simulated cluster samples using the same methods used on the XCS data. Our data favour models in which the majority of the excess entropy required to explain the slope of the LX - T relation is injected at high redshift. Simulations in which active galactic nucleus feedback is implemented using prescriptions from current semi-analytic galaxy formation models predict the positive evolution of the normalization, and differ from our data at more than 5 sigma. This suggests that more efficient feedback at high redshift may be needed in these models.
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| 9. |
- Hilton, Matt, et al.
(författare)
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THE XMM CLUSTER SURVEY : ACTIVE GALACTIC NUCLEI AND STARBURST GALAXIES IN XMMXCS J2215.9-1738 AT z=1.46
- 2010
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Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 718:1, s. 133-147
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Tidskriftsartikel (refereegranskat)abstract
- We use Chandra X-ray and Spitzer infrared (IR) observations to explore the active galactic nucleus (AGN) and starburst populations of XMMXCS J2215.9-1738 at z = 1.46, one of the most distant spectroscopically confirmed galaxy clusters known. The high-resolution X-ray imaging reveals that the cluster emission is contaminated by point sources that were not resolved in XMM-Newton observations of the system, and have the effect of hardening the spectrum, leading to the previously reported temperature for this system being overestimated. From a joint spectroscopic analysis of the Chandra and XMM-Newton data, the cluster is found to have temperature T = 4.1(-0.9)(+0.6) keV and luminosity LX = (2.92(-0.35)(+0.24)) x 1044 erg s(-1), extrapolated to a radius of 2 Mpc. As a result of this revised analysis, the cluster is found to lie on the sigma(v)-T relation, but the cluster remains less luminous than would be expected from self-similar evolution of the local L-X-T relation. Two of the newly discovered X-ray AGNs are cluster members, while a third object, which is also a prominent 24 mu m source, is found to have properties consistent with it being a high-redshift, highly obscured object in the background. We find a total of eight > 5 sigma 24 mu m sources associated with cluster members (four spectroscopically confirmed and four selected using photometric redshifts) and one additional 24 mu m source with two possible optical/near-IR counterparts that may be associated with the cluster. Examining the Infrared Array Camera colors of these sources, we find that one object is likely to be an AGN. Assuming that the other 24 mu m sources are powered by star formation, their IR luminosities imply star formation rates similar to 100 M-circle dot yr(-1). We find that three of these sources are located at projected distances of <250 kpc from the cluster center, suggesting that a large amount of star formation may be taking place in the cluster core, in contrast to clusters at low redshift.
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| 10. |
- Hunter, Amanda, et al.
(författare)
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Effect of wood smoke exposure on vascular function and thrombus formation in healthy fire fighters
- 2014
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Ingår i: Particle and Fibre Toxicology. - : BioMed Central (BMC). - 1743-8977. ; 11
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Tidskriftsartikel (refereegranskat)abstract
- Background: Myocardial infarction is the leading cause of death in fire fighters and has been linked with exposure to air pollution and fire suppression duties. We therefore investigated the effects of wood smoke exposure on vascular vasomotor and fibrinolytic function, and thrombus formation in healthy fire fighters. Methods: In a double-blind randomized cross-over study, 16 healthy male fire fighters were exposed to wood smoke (~1 mg/m3 particulate matter concentration) or filtered air for one hour during intermittent exercise. Arterial pressure and stiffness were measured before and immediately after exposure, and forearm blood flow was measured during intra-brachial infusion of endothelium-dependent and -independent vasodilators 4–6 hours after exposure. Thrombus formation was assessed using the ex vivo Badimon chamber at 2 hours, and platelet activation was measured using flow cytometry for up to 24 hours after the exposure. Results: Compared to filtered air, exposure to wood smoke increased blood carboxyhaemoglobin concentrations (1.3% versus 0.8%; P < 0.001), but had no effect on arterial pressure, augmentation index or pulse wave velocity (P > 0.05 for all). Whilst there was a dose-dependent increase in forearm blood flow with each vasodilator (P < 0.01 for all), there were no differences in blood flow responses to acetylcholine, sodium nitroprusside or verapamil between exposures (P > 0.05 for all). Following exposure to wood smoke, vasodilatation to bradykinin increased (P = 0.003), but there was no effect on bradykinin-induced tissue-plasminogen activator release, thrombus area or markers of platelet activation (P > 0.05 for all). Conclusions: Wood smoke exposure does not impair vascular vasomotor or fibrinolytic function, or increase thrombus formation in fire fighters. Acute cardiovascular events following fire suppression may be precipitated by exposure to other air pollutants or through other mechanisms, such as strenuous physical exertion and dehydration.
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| 11. |
- Jones, Felicity C., et al.
(författare)
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The genomic basis of adaptive evolution in threespine sticklebacks
- 2012
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 484:7392, s. 55-61
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Tidskriftsartikel (refereegranskat)abstract
- Marine stickleback fish have colonized and adapted to thousands of streams and lakes formed since the last ice age, providing an exceptional opportunity to characterize genomic mechanisms underlying repeated ecological adaptation in nature. Here we develop a high-quality reference genome assembly for threespine sticklebacks. By sequencing the genomes of twenty additional individuals from a global set of marine and freshwater populations, we identify a genome-wide set of loci that are consistently associated with marine-freshwater divergence. Our results indicate that reuse of globally shared standing genetic variation, including chromosomal inversions, has an important role in repeated evolution of distinct marine and freshwater sticklebacks, and in the maintenance of divergent ecotypes during early stages of reproductive isolation. Both coding and regulatory changes occur in the set of loci underlying marine-freshwater evolution, but regulatory changes appear to predominate in this well known example of repeated adaptive evolution in nature.
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| 12. |
- Lloyd-Davies, E. J., et al.
(författare)
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The XMM Cluster Survey : X-ray analysis methodology
- 2011
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Ingår i: Monthly notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 418:1, s. 14-53
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Tidskriftsartikel (refereegranskat)abstract
- The XMM Cluster Survey (XCS) is a serendipitous search for galaxy clusters using all publicly available data in the XMMNewton Science Archive. Its main aims are to measure cosmological parameters and trace the evolution of X-ray scaling relations. In this paper we describe the data processing methodology applied to the 5776 XMM observations used to construct the current XCS source catalogue. A total of 3675 > 4s cluster candidates with > 50 background-subtracted X-ray counts are extracted from a total non-overlapping area suitable for cluster searching of 410 deg2. Of these, 993 candidates are detected with > 300 background-subtracted X-ray photon counts, and we demonstrate that robust temperature measurements can be obtained down to this count limit. We describe in detail the automated pipelines used to perform the spectral and surface brightness fitting for these candidates, as well as to estimate redshifts from the X-ray data alone. A total of 587 (122) X-ray temperatures to a typical accuracy of < 40 (< 10) per cent have been measured to date. We also present the methodology adopted for determining the selection function of the survey, and show that the extended source detection algorithm is robust to a range of cluster morphologies by inserting mock clusters derived from hydrodynamical simulations into real XMMimages. These tests show that the simple isothermal beta-profiles is sufficient to capture the essential details of the cluster population detected in the archival XMM observations. The redshift follow-up of the XCS cluster sample is presented in a companion paper, together with a first data release of 503 optically confirmed clusters.
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| 13. |
- Mandt, Kathleen E., et al.
(författare)
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Ion densities and composition of Titan's upper atmosphere derived from the Cassini Ion Neutral Mass Spectrometer : Analysis methods and comparison of measured ion densities to photochemical model simulations
- 2012
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Ingår i: Journal of Geophysical Research. - 0148-0227 .- 2156-2202. ; 117, s. E10006-
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Tidskriftsartikel (refereegranskat)abstract
- The Cassini Ion Neutral Mass Spectrometer (INMS) has measured both neutral and ion species in Titan's upper atmosphere and ionosphere and the Enceladus plumes. Ion densities derived from INMS measurements are essential data for constraining photochemical models of Titan's ionosphere. The objective of this paper is to present an optimized method for converting raw data measured by INMS to ion densities. To do this, we conduct a detailed analysis of ground and in-flight calibration to constrain the instrument response to ion energy, the critical parameter on which the calibration is based. Data taken by the Cassini Radio Plasma Wave Science Langmuir Probe and the Cassini Plasma Spectrometer Ion Beam Spectrometer are used as independent measurement constraints in this analysis. Total ion densities derived with this method show good agreement with these data sets in the altitude region (similar to 1100-1400 km) where ion drift velocities are low and the mass of the ions is within the measurement range of the INMS (1-99 Daltons). Although ion densities calculated by the method presented here differ slightly from those presented in previous INMS publications, we find that the implications for the science presented in previous publications is mostly negligible. We demonstrate the role of the INMS ion densities in constraining photochemical models and find that (1) cross sections having high resolution as a function of wavelength are necessary for calculating the initial photoionization products and (2) there are disagreements between the measured ion densities representative of the initial steps in Titan photochemistry that require further investigation.
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| 14. |
- Mehrtens, Nicola, et al.
(författare)
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The XMM Cluster Survey : optical analysis methodology and the first data release
- 2012
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Ingår i: Monthly notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 423:2, s. 1024-1052
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Tidskriftsartikel (refereegranskat)abstract
- The XMM Cluster Survey (XCS) is a serendipitous search for galaxy clusters using all publicly available data in the XMMNewton Science Archive. Its main aims are to measure cosmological parameters and trace the evolution of X-ray scaling relations. In this paper we present the first data release from the XMM Cluster Survey (XCS-DR1). This consists of 503 optically confirmed, serendipitously detected, X-ray clusters. Of these clusters, 256 are new to the literature and 357 are new X-ray discoveries. We present 463 clusters with a redshift estimate (0.06 < z < 1.46), including 261 clusters with spectroscopic redshifts. The remainder have photometric redshifts. In addition, we have measured X-ray temperatures (TX) for 401 clusters (0.4 < TX < 14.7 keV). We highlight seven interesting subsamples of XCS-DR1 clusters: (i) 10 clusters at high redshift (z > 1.0, including a new spectroscopically confirmed cluster at z= 1.01); (ii) 66 clusters with high TX (>5 keV); (iii) 130 clusters/groups with low TX (<2 keV); (iv) 27 clusters with measured TX values in the Sloan Digital Sky Survey (SDSS) Stripe 82 co-add region; (v) 77 clusters with measured TX values in the Dark Energy Survey region; (vi) 40 clusters detected with sufficient counts to permit mass measurements (under the assumption of hydrostatic equilibrium); (vii) 104 clusters that can be used for applications such as the derivation of cosmological parameters and the measurement of cluster scaling relations. The X-ray analysis methodology used to construct and analyse the XCS-DR1 cluster sample has been presented in a companion paper, Lloyd-Davies et al.
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| 15. |
- Weeks, Andrew R., et al.
(författare)
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Assessing the benefits and risks of translocations in changing environments : a genetic perspective
- 2011
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Ingår i: Evolutionary Applications. - : Wiley. - 1752-4571. ; 4:6, s. 709-725
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Tidskriftsartikel (refereegranskat)abstract
- Translocations are being increasingly proposed as a way of conserving biodiversity, particularly in the management of threatened and keystone species, with the aims of maintaining biodiversity and ecosystem function under the combined pressures of habitat fragmentation and climate change. Evolutionary genetic considerations should be an important part of translocation strategies, but there is often confusion about concepts and goals. Here, we provide a classification of translocations based on specific genetic goals for both threatened species and ecological restoration, separating targets based on ‘genetic rescue’ of current population fitness from those focused on maintaining adaptive potential. We then provide a framework for assessing the genetic benefits and risks associated with translocations and provide guidelines for managers focused on conserving biodiversity and evolutionary processes. Case studies are developed to illustrate the framework.
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