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| 4. |
- Campbell, PJ, et al.
(författare)
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Pan-cancer analysis of whole genomes
- 2020
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 578:7793, s. 82-
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Tidskriftsartikel (refereegranskat)abstract
- Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale1–3. Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4–5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter4; identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation5,6; analyses timings and patterns of tumour evolution7; describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity8,9; and evaluates a range of more-specialized features of cancer genomes8,10–18.
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| 5. |
- Razavi, H., et al.
(författare)
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Hepatitis C virus prevalence and level of intervention required to achieve the WHO targets for elimination in the European Union by 2030: a modelling study
- 2017
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Ingår i: Lancet Gastroenterology & Hepatology. - : Elsevier BV. - 2468-1253. ; 2:5, s. 325-336
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Tidskriftsartikel (refereegranskat)abstract
- Background Hepatitis C virus (HCV) is a leading cause of liver-related morbidity and mortality worldwide. In the European Union (EU), treatment and cure of HCV with direct-acting antiviral therapies began in 2014. WHO targets are to achieve a 65% reduction in liver-related deaths, a 90% reduction of new viral hepatitis infections, and 90% of patients with viral hepatitis infections being diagnosed by 2030. This study assessed the prevalence of HCV in the EU and the level of intervention required to achieve WHO targets for HCV elimination. Methods We populated country Markov models for the 28 EU countries through a literature search of PubMed and Embase between Jan 1, 2000, and March 31, 2016, and a Delphi process to gain expert consensus and validate inputs. We aggregated country models to create a regional EU model. We used the EU model to forecast HCV disease progression (considering the effect of immigration) and developed a strategy to acehive WHO targets. We used weighted average sustained viral response rates and fibrosis restrictions to model the effect of current therapeutic guidelines. We used the EU model to forecast HCV disease progression (considering the effect of immigration) under current screening and therapeutic guidelines. Additionally, we back-calculated the total number of patients needing to be screened and treated to achieve WHO targets. Findings We estimated the number of viraemic HCV infections in 2015 to be 3 238 000 (95% uncertainty interval [UI] 2 106 000-3 795 000) of a total population of 509 868 000 in the EU, equating to a prevalence of viraemic HCV of 0.64% (95% UI 0.41-0.74). We estimated that 1 180 000 (95% UI 1 003 000-1 357 000) people were diagnosed with viraemia (36.4%), 150 000 (12 000-180 000) were treated (4.6% of the total infected population or 12.7% of the diagnosed population), 133 000 (106 000-160 000) were cured (4.1%), and 57 900 (43 900-67 300) were newly infected (1.8%) in 2015. Additionally, 30 400 (26 600-42 500) HCV-positive immigrants entered the EU. To achieve WHO targets, unrestricted treatment needs to increase from 150 000 patients in 2015 to 187 000 patients in 2025 and diagnosis needs to increase from 88 800 new cases annually in 2015 to 180 000 in 2025. Interpretation Given its advanced health-care infrastructure, the EU is uniquely poised to eliminate HCV; however, expansion of screening programmes is essential to increase treatment to achieve the WHO targets. A united effort, grounded in sound epidemiological evidence, will also be necessary.
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- Yakneen, S, et al.
(författare)
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Butler enables rapid cloud-based analysis of thousands of human genomes
- 2020
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Ingår i: Nature biotechnology. - : Springer Science and Business Media LLC. - 1546-1696 .- 1087-0156. ; 38:3, s. 288-
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Tidskriftsartikel (refereegranskat)abstract
- We present Butler, a computational tool that facilitates large-scale genomic analyses on public and academic clouds. Butler includes innovative anomaly detection and self-healing functions that improve the efficiency of data processing and analysis by 43% compared with current approaches. Butler enabled processing of a 725-terabyte cancer genome dataset from the Pan-Cancer Analysis of Whole Genomes (PCAWG) project in a time-efficient and uniform manner.
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| 14. |
- Magiorkinis, G, et al.
(författare)
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The global spread of HIV-1 subtype B epidemic
- 2016
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Ingår i: Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases. - : Elsevier BV. - 1567-7257. ; 46, s. 169-179
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Tidskriftsartikel (refereegranskat)
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- Anzt, Hartwig, et al.
(författare)
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An environment for sustainable research software in Germany and beyond: current state, open challenges, and call for action
- 2020
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Ingår i: F1000 Research. - : F1000 Research Ltd. - 2046-1402. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- Research software has become a central asset in academic research. It optimizes existing and enables new research methods, implements and embeds research knowledge, and constitutes an essential research product in itself. Research software must be sustainable in order to understand, replicate, reproduce, and build upon existing research or conduct new research effectively. In other words, software must be available, discoverable, usable, and adaptable to new needs, both now and in the future. Research software therefore requires an environment that supports sustainability. Hence, a change is needed in the way research software development and maintenance are currently motivated, incentivized, funded, structurally and infrastructurally supported, and legally treated. Failing to do so will threaten the quality and validity of research. In this paper, we identify challenges for research software sustainability in Germany and beyond, in terms of motivation, selection, research software engineering personnel, funding, infrastructure, and legal aspects. Besides researchers, we specifically address political and academic decision-makers to increase awareness of the importance and needs of sustainable research software practices. In particular, we recommend strategies and measures to create an environment for sustainable research software, with the ultimate goal to ensure that software-driven research is valid, reproducible and sustainable, and that software is recognized as a first class citizen in research. This paper is the outcome of two workshops run in Germany in 2019, at deRSE19 - the first International Conference of Research Software Engineers in Germany - and a dedicated DFG-supported follow-up workshop in Berlin.
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| 26. |
- Bachmann, L., et al.
(författare)
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The role of systematics for understanding ecosystem functions: Proceedings of the Zoologica Scripta Symposium, Oslo, Norway, 25 August 2022
- 2023
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Ingår i: Zoologica Scripta. - : Wiley. - 0300-3256 .- 1463-6409. ; 52:3, s. 187-214
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Tidskriftsartikel (refereegranskat)abstract
- On 25 August 2022, the Zoologica Scripta - An International Journal of Systematic Zoology and the Norwegian Academy of Sciences and Letters arranged a symposium entitled 'The role of systematics for understanding ecosystem functions' in the Academy's premises in Oslo, Norway. The symposium aimed at offering a forum for exploring and discussing trends and future developments in the field of systematics. Eleven international experts contributed expertise on various issues related to global challenges, such as biodiversity assessments, databases, cutting-edge analysis tools, and the consequences of the taxonomic impediment. Here, we compiled a multi-author proceedings paper of the symposium contributions that are arranged in chapters and presents the content and the key conclusions of the majority of the presentations.
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| 27. |
- Cerca, José, et al.
(författare)
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Incomplete lineage sorting and ancient admixture, and speciation without morphological change in ghost-worm cryptic species
- 2021
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Ingår i: PeerJ. - : PeerJ. - 2167-8359. ; 9, s. e10896-e10896
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Tidskriftsartikel (refereegranskat)abstract
- Morphologically similar species, that is cryptic species, may be similar or quasi-similar owing to the deceleration of morphological evolution and stasis. While the factors underlying the deceleration of morphological evolution or stasis in cryptic species remain unknown, decades of research in the field of paleontology on punctuated equilibrium have originated clear hypotheses. Species are expected to remain morphologically identical in scenarios of shared genetic variation, such as hybridization and incomplete lineage sorting, or in scenarios where bottlenecks reduce genetic variation and constrain the evolution of morphology. Here, focusing on three morphologically similar Stygocapitella species, we employ a whole-genome amplification method (WGA) coupled with double-digestion restriction-site associated DNA sequencing (ddRAD) to reconstruct the evolutionary history of the species complex. We explore population structure, use population-level statistics to determine the degree of connectivity between populations and species, and determine the most likely demographic scenarios which generally reject for recent hybridization. We find that the combination of WGA and ddRAD allowed us to obtain genomic-level data from microscopic eukaryotes (∼1 millimetre) opening up opportunities for those working with population genomics and phylogenomics in such taxa. The three species share genetic variance, likely from incomplete lineage sorting and ancient admixture. We speculate that the degree of shared variation might underlie morphological similarity in the Atlantic species complex.
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| 29. |
- Dusart, Philip, et al.
(författare)
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A systems-approach reveals human nestin is an endothelial-enriched, angiogenesis-independent intermediate filament protein
- 2018
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Ingår i: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 8:1
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Tidskriftsartikel (refereegranskat)abstract
- The intermediate filament protein nestin is expressed during embryonic development, but considered largely restricted to areas of regeneration in the adult. Here, we perform a body-wide transcriptome and protein-profiling analysis to reveal that nestin is constitutively, and highly-selectively, expressed in adult human endothelial cells (EC), independent of proliferative status. Correspondingly, we demonstrate that it is not a marker for tumour EC in multiple malignancy types. Imaging of EC from different vascular beds reveals nestin subcellular distribution is shear-modulated. siRNA inhibition of nestin increases EC proliferation, and nestin expression is reduced in atherosclerotic plaque neovessels. eQTL analysis reveals an association between SNPs linked to cardiovascular disease and reduced aortic EC nestin mRNA expression. Our study challenges the dogma that nestin is a marker of proliferation, and provides insight into its regulation and function in EC. Furthermore, our systems-based approach can be applied to investigate body-wide expression profiles of any candidate protein.
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| 30. |
- Elmegreen, B.G., et al.
(författare)
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Dust Spirals and Acoustic Noise in the Nucleus of the Galaxy NGC 2207
- 1998
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Ingår i: Astrophysical Journal. - : American Astronomical Society. - 1538-4357 .- 0004-637X. ; 503:2, s. L119-L122
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Tidskriftsartikel (refereegranskat)abstract
- Observations with the Hubble Space Telescope reveal an irregular network of dust spiral arms in the nuclear region of the interacting disk galaxy NGC 2207. The spirals extend from ~50 to ~300 pc in galactocentric radius, with a projected width of ~20 pc. Radiative transfer calculations determine the gas properties of the spirals and the inner disk and imply a factor of ~4 local gas compression in the spirals. The gas is not strongly self-gravitating, nor is there a nuclear bar, so the spirals could not have formed by the usual mechanisms applied to main galaxy disks. Instead, they may result from acoustic instabilities that amplify at small galactic radii. Such instabilities may promote gas accretion into the nucleus.
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| 31. |
- Elmegreen, B.G., et al.
(författare)
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Hubble Space Telescope Observations of the Interacting Galaxies NGC 2207 and IC 2163
- 2000
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Ingår i: Astronomical Journal. - : American Astronomical Society. - 1538-3881 .- 0004-6256. ; 120:2, s. 630-644
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Tidskriftsartikel (refereegranskat)abstract
- Hubble Space Telescope (HST) images of the galaxies NGC 2207 and IC 2163 show star formation and dust structures in a system that has experienced a recent grazing encounter. Tidal forces from NGC 2207 compressed and elongated the disk of IC 2163, forming an oval ridge of star formation along a caustic where the perturbed gas rebounded after its inward excursion. Gas flowing away from this ridge has a peculiar structure characterized by thin parallel dust filaments transverse to the direction of motion. The filaments become thicker and longer as the gas approaches the tidal arm. Star formation that occurs in the filaments consistently lags behind, as if the exponential disk pressure gradient pushes outward on the gas but not on the young stars. Numerical models suggest that the filaments come from flocculent spiral arms that were present before the interaction. The arms stretch out into parallel filaments as the tidal tail forms. A dust lane at the outer edge of the tidal tail is a shock front where the flow abruptly changes direction. Gas at small-to-intermediate radii along this edge flows back toward the galaxy, while elsewhere in the tidal arm, the gas flows outward.A spiral arm of NGC 2207 that is backlit by IC 2163 is seen with HST to contain several parallel, knotty filaments spanning the full width of the arm. These filaments are probably shock fronts in a density wave. The parallel structure suggests that the shocks occur in several places throughout the arm, or that the interarm gas is composed of spiral-like wisps that merge together in the arms. Blue clusters of star formation inside the clumps of these dust lanes show density-wave triggering in unprecedented detail. The star formation process seems to be one of local gravitational collapse, rather than cloud collisions. Spiral arms inside the oval of IC 2163 have a familiar geometry reminiscent of a bar, although there is no obvious stellar bar. The shape and orientation of these arms suggest they could be the result of inner Lindblad resonance–related orbits in the cos 2θ tidal potential that formed the oval. Their presence suggests that tidal forces alone may initiate a temporary nuclear gas flow and eventual starburst without first forming a stellar bar. Several emission structures resembling jets or conical flows that are 100–1000 pc long appear in these galaxies. In the western arm of NGC 2207, there is a dense dark cloud with a conical shape 400 pc long and a bright compact cluster at the tip, and there is a conical emission nebula of the same length that points away from the cluster in the other direction. This region also coincides with a nonthermal radio continuum source that is ~1000 times the luminosity of Cas A at λ = 20 cm. Surrounding clusters in arclike patterns may have been triggered by enormous explosions.
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| 32. |
- Elmegreen, D.M., et al.
(författare)
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Hubble Space Telescope Observations of Dust and Star-forming Regions in the Ocular Galaxy IC 2163 and Its Spiral Companion NGC 2207
- 2001
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Ingår i: Astronomical Journal. - : American Astronomical Society. - 1538-3881 .- 0004-6256. ; 121:1, s. 182-197
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Tidskriftsartikel (refereegranskat)abstract
- Hubble Space Telescope observations in U, B, V, and I passbands of the interacting spiral galaxies IC 2163 and NGC 2207 are used to measure extinctions in the cloud and intercloud regions and ages and luminosities of the star-forming regions. The extinction in the part of NGC 2207 seen in projection against IC 2163 was determined by using the method of White & Keel. The extinctions there and elsewhere were also determined from radiative transfer models of the magnitude differences between clouds and their surroundings. The intercloud extinction in V band ranges from 0.5 to 1 mag on the line of sight, and the cloud extinction ranges from 1 to 2 mag. The measured star-forming regions in these galaxies have a power-law relation between size and luminosity and a power-law luminosity distribution function. These power laws are consistent with a fractal dimension for the star formation that is the same as that for interstellar gas, D ~ 2.2, extending over scales ranging from 20 to 1000 pc. Fifteen compact massive star clusters that are analogous to super–star clusters found in starburst regions are in the spiral arms of NGC 2207. Nothing is peculiar about these regions except for a high H I velocity dispersion (~50 km s-1). Two more super–star clusters are in the tidally compressed oval of IC 2163. These clusters have masses ranging from ~10^4 to 2 × 10^5 M⊙ and ages of a few times 10^6 yr.
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| 33. |
- Kaufman, M., et al.
(författare)
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CO observations of the interacting galaxy pair NGC 5394/95
- 2002
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Ingår i: Astronomical Journal. - : American Astronomical Society. - 1538-3881 .- 0004-6256. ; 123:2 1754, s. 702-719
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Tidskriftsartikel (refereegranskat)abstract
- BIMA 12CO J = 1 → 0 observations are presented of the spiral galaxies NGC 5394 and NGC 5395 that have undergone a recent, grazing encounter. In NGC 5394 approximately 80% of the CO emission detected by BIMA is concentrated in the central 800 pc (FWHM) starburst region, and the rest is from a portion of the inner disk south and west of the central starburst. In an encounter simulation that reproduces some of the main features of this galaxy pair, a considerable amount of gas in NGC 5394 falls into the central region early in the collision. The observed total gas distribution in the disk of NGC 5394 is lopsided, with more H I, CO, and Hα emission coming from the western or southwestern side. The innermost western arm of NGC 5394 is seen in CO and Hα emission, but the eastern inner-disk arm, which is very bright in the optical continuum, is not detected in CO or Hα emission. The NGC 5394 starburst region is similar in radio continuum luminosity and size to the M82 starburst and has a CO luminosity ∼4 times greater. A CO position-velocity diagram of the NGC 5394 nucleus reveals two separate velocity features very close to the center. This may indicate a nuclear ring or the "twin peaks" of an ILR or some depletion of 12CO J = 1 → 0 at the nucleus. From a comparison of the radio continuum, Hα, 60 μm, and CO luminosities, we estimate that the average extinction A v of the starburst nucleus is 3-4 mag, the star formation rate is ∼6 M⊙ yr-1, and the conversion factor N(H 2)/ICO in the starburst is a factor of 3-4 below the standard value. Comparison of NGC 5394 with two other systems previously studied suggests that in prograde grazing encounters a central starburst may not develop until near the end of the ocular phase. Very little of the CO emission from NGC 5395 found in previous single-dish observations is detected in the BIMA data; thus molecular gas in NGC 5395 does not appear to be strongly concentrated in compressed ridges.
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| 34. |
- Kaufman, M., et al.
(författare)
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Observations of the Ocular Galaxy NGC 2535 and its Starburst Companion NGC 2536
- 1997
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Ingår i: Astronomical Journal. - : American Astronomical Society. - 1538-3881 .- 0004-6256. ; 114, s. 2323-2349
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Tidskriftsartikel (refereegranskat)abstract
- H I, radio continuum, and 12CO J=1-->0 observations at resolutions of 12" to 33" (=2.9-8 kpc), and B, I, J, and K-band images, are presented of the galaxy NGC 2535 and its small starburst companion NGC 2536. NGC 2535 has an ocular (eye-shaped) structure with two long tidal arms indicative of a recent, close, nonmerging encounter. Our observations reveal widespread high velocity dispersions (30 km s-1) in the H I gas and five clouds with masses of ˜10^8 Msun in the tidal arms of NGC 2535. These clouds do not correspond to the most luminous blue knots or to major clumps in the old stellar population. Similar phenomena were found previously in other pairs (IC 2163/NGC 2207 and NGC 5774/5), suggesting that enhanced turbulence and massive gas clouds may be a general feature of interacting spiral galaxies during an early phase of post-encounter evolution. A search for 12CO J= 1-->O emission at 11 positions in NGC 2535 and one position in NGC 2536 yielded two clear detections, one at the center of NGC 2535 and the other on its tidal tail but close to the center of NGC 2535. Most of the massive H I clouds in NGC 2535 are not detected in CO emission. The virial masses of these clouds are significantly greater than their measured masses in gas, presumably because of the presence of old disk stars in the clouds. A form of the virial theorem that includes gas and stars is presented. NGC 2535 shows several unusual features, including an intrinsically oval shape to the disk, that are similar to those in the ocular galaxy IC 2163 studied previously. NGC 2535 also contains structures that are not seen in IC 2163. For example, there is an extended (R =48 kpc) H I envelope and a long, outer, elliptically-shaped H I arc in NGC 2535 that may be a gravitational wake produced by the passage of the companion within or close to the envelope. In the radio continuum, NGC 2535 exhibits a bar-like feature that leads the small stellar bar by 50°. The starburst companion, NGC 2536, lies in a 2 X 10^9 Msun clump of H I gas at the outer end of the tidal bridge from NGC 2535. Most of the gas in this clump is associated with the bridge. The H I emission on the anticompanion side of NGC 2536 has the same line-of-sight velocity and projected position as some of the bridge gas there. This observation is consistent with a previous model by Klaric in which NGC 2536 accretes gas from NGC 2535; we even find an H I feature that may represent bridge gas streaming towards NGC 2536. The failure to detect 12CO emission in NGC 2536 places an upper limit of 6 X H2 on its H2 mass if the standard value of the conversion factor between I_CO and N(H2) applies.
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| 35. |
- Kaufman, M., et al.
(författare)
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The Interacting Galaxies NGC 5394/5395: A Post-Ocular Galaxy and Its Ring/Spiral Companion
- 1999
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Ingår i: Astronomical Journal. - : American Astronomical Society. - 1538-3881 .- 0004-6256. ; 118:4, s. 1577-1608
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Tidskriftsartikel (refereegranskat)abstract
- H I, radio continuum, Fabry-Perot Hα, and 12CO J = 1 → 0 observations and broadband optical and near infrared images are presented of the interacting spiral galaxies NGC 5395 and NGC 5394. Kinematically, there are three important, separate components to the H I gas associated with this galaxy pair: (1) the main disk of NGC 5395, (2) a long, northern tidal arm of NGC 5395 distinct in velocity from its main disk, and (3) the disk of NGC 5394. The H I northern tidal arm of NGC 5395 has a line of–sight velocity as much as 75–100 km s-1 greater than the main disk of NGC 5395 at the same projected location and thus is not in the same plane as the disk. The velocity field of the disk of NGC 5395 is asymmetric and distorted by large-scale and small-scale noncircular motions. In NGC 5395, the encounter appears to be exciting m = 1 and m = 0 modes in what had been a two-armed spiral. The dominant spiral arm of NGC 5395 forms a large ring or pseudo-ring of Hα, radio continuum, and H I emission, somewhat off center with respect to the nucleus. The H I trough in the center of NGC 5395 is not filled in by molecular gas. The Hα velocity contours exhibit an organized pattern of kinks in crossing the ring and also show streaming motions in a large stellar caustic feature. The eastern side of the ring is brighter in radio continuum and Hα; the western side is brighter in H I and contains massive (108 M☉) H I clouds not associated with the most luminous H II regions. The smaller galaxy NGC 5394 is in an immediate post-ocular phase, with a central starburst, an intrinsically oval disk, two long, fairly symmetric, open tidal arms with high arm-interarm contrast, and very bright inner spiral arms, disjoint from the outer tidal arms. Most of the gas in NGC 5394 is in molecular form and concentrated within 3.8 kpc of the center, so is suitable for fueling the starburst. Despite the presence of H I gas, two of the three optically bright inner spiral arms of NGC 5394 show no evidence of ongoing star formation.A galaxy encounter simulation reproduces some of the main features of this system with a collision that is prograde relative to NGC 5394 and retrograde at a high tilt angle relative to NGC 5395. The model finds that the inner spiral structure of NGC 5394 developed from an eye-shaped ("ocular") structure at slightly earlier times. NGC 5394 and the two ocular galaxies IC 2163 and NGC 2535, studied earlier, form an evolutionary sequence of structures resulting from prograde encounters and thus confirm the generic models of such collisions. The agreement between the model for NGC 5394/95 and the ring/spiral structures seen in NGC 5395 extends our understanding of collisional ring galaxies.
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| 36. |
- Newton-Cheh, Christopher, et al.
(författare)
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Association of common variants in NPPA and NPPB with circulating natriuretic peptides and blood pressure
- 2009
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 41:3, s. 348-353
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Tidskriftsartikel (refereegranskat)abstract
- We examined the association of common variants at the NPPA-NPPB locus with circulating concentrations of the natriuretic peptides, which have blood pressure-lowering properties. We genotyped SNPs at the NPPA-NPPB locus in 14,743 individuals of European ancestry, and identified associations of plasma atrial natriuretic peptide with rs5068 (P = 8 x 10(-70)), rs198358 (P = 8 x 10(-30)) and rs632793 (P = 2 x 10(-10)), and of plasma B-type natriuretic peptide with rs5068 (P = 3 x 10(-12)), rs198358 (P = 1 x 10(-25)) and rs632793 (P = 2 x 10(-68)). In 29,717 individuals, the alleles of rs5068 and rs198358 that showed association with increased circulating natriuretic peptide concentrations were also found to be associated with lower systolic (P = 2 x 10(-6) and 6 x 10(-5), respectively) and diastolic blood pressure (P = 1 x 10(-6) and 5 x 10(-5)), as well as reduced odds of hypertension (OR = 0.85, 95% CI = 0.79-0.92, P = 4 x 10(-5); OR = 0.90, 95% CI = 0.85-0.95, P = 2 x 10(-4), respectively). Common genetic variants at the NPPA-NPPB locus found to be associated with circulating natriuretic peptide concentrations contribute to interindividual variation in blood pressure and hypertension.
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| 37. |
- Oette, M, et al.
(författare)
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Efficacy of antiretroviral therapy switch in HIV-infected patients: a 10-year analysis of the EuResist Cohort
- 2012
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Ingår i: Intervirology. - : S. Karger AG. - 1423-0100 .- 0300-5526. ; 55:2, s. 160-166
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Tidskriftsartikel (refereegranskat)abstract
- <i>Introduction:</i> Highly active antiretroviral therapy (HAART) has been shown to be effective in many recent trials. However, there is limited data on time trends of HAART efficacy after treatment change. <i>Methods:</i> Data from different European cohorts were compiled within the EuResist Project. The efficacy of HAART defined by suppression of viral replication at 24 weeks after therapy switch was analyzed considering previous treatment modifications from 1999 to 2008. <i>Results:</i> Altogether, 12,323 treatment change episodes in 7,342 patients were included in the analysis. In 1999, HAART after treatment switch was effective in 38.0% of the patients who had previously undergone 1–5 therapies. This figure rose to 85.0% in 2008. In patients with more than 5 previous therapies, efficacy rose from 23.9 to 76.2% in the same time period. In patients with detectable viral load at therapy switch, the efficacy rose from 23.3 to 66.7% with 1–5 previous treatments and from 14.4 to 55.6% with more than 5 previous treatments. <i>Conclusion:</i> The results of this large cohort show that the outcome of HAART switch has improved considerably over the last years. This result was particularly observed in the context after viral rebound. Thus, changing HAART is no longer associated with a high risk of treatment failure.
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