| 1. |
- Antoniou, A. C., et al.
(författare)
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Common breast cancer susceptibility alleles and the risk of breast cancer for BRCA1 and BRCA2 mutation carriers : Implications for risk prediction
- 2010
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Ingår i: Cancer Research. - : American Association for Cancer Research. - 0008-5472 .- 1538-7445. ; 70:23, s. 9742-9754
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Tidskriftsartikel (refereegranskat)abstract
- The known breast cancer susceptibility polymorphisms in FGFR2, TNRC9/TOX3, MAP3K1, LSP1, and 2q35 confer increased risks of breast cancer for BRCA1 or BRCA2 mutation carriers. We evaluated the associations of 3 additional single nucleotide polymorphisms (SNPs), rs4973768 in SLC4A7/NEK10, rs6504950 in STXBP4/COX11, and rs10941679 at 5p12, and reanalyzed the previous associations using additional carriers in a sample of 12,525 BRCA1 and 7,409 BRCA2 carriers. Additionally, we investigated potential interactions between SNPs and assessed the implications for risk prediction. The minor alleles of rs4973768 and rs10941679 were associated with increased breast cancer risk for BRCA2 carriers (per-allele HR = 1.10, 95% CI: 1.03-1.18, P = 0.006 and HR = 1.09, 95% CI: 1.01-1.19, P = 0.03, respectively). Neither SNP was associated with breast cancer risk for BRCA1 carriers, and rs6504950 was not associated with breast cancer for either BRCA1 or BRCA2 carriers. Of the 9 polymorphisms investigated, 7 were associated with breast cancer for BRCA2 carriers (FGFR2, TOX3, MAP3K1, LSP1, 2q35, SLC4A7, 5p12, P = 7 × 10-11 - 0.03), but only TOX3 and 2q35 were associated with the risk for BRCA1 carriers (P = 0.0049, 0.03, respectively). All risk-associated polymorphisms appear to interact multiplicatively on breast cancer risk for mutation carriers. Based on the joint genotype distribution of the 7 risk-associated SNPs in BRCA2 mutation carriers, the 5% of BRCA2 carriers at highest risk (i.e., between 95th and 100th percentiles) were predicted to have a probability between 80% and 96% of developing breast cancer by age 80, compared with 42% to 50% for the 5% of carriers at lowest risk. Our findings indicated that these risk differences might be sufficient to influence the clinical management of mutation carriers.
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| 2. |
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| 3. |
- Lango Allen, Hana, et al.
(författare)
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Hundreds of variants clustered in genomic loci and biological pathways affect human height.
- 2010
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 467:7317, s. 832-8
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Tidskriftsartikel (refereegranskat)abstract
- Most common human traits and diseases have a polygenic pattern of inheritance: DNA sequence variants at many genetic loci influence the phenotype. Genome-wide association (GWA) studies have identified more than 600 variants associated with human traits, but these typically explain small fractions of phenotypic variation, raising questions about the use of further studies. Here, using 183,727 individuals, we show that hundreds of genetic variants, in at least 180 loci, influence adult height, a highly heritable and classic polygenic trait. The large number of loci reveals patterns with important implications for genetic studies of common human diseases and traits. First, the 180 loci are not random, but instead are enriched for genes that are connected in biological pathways (P = 0.016) and that underlie skeletal growth defects (P<0.001). Second, the likely causal gene is often located near the most strongly associated variant: in 13 of 21 loci containing a known skeletal growth gene, that gene was closest to the associated variant. Third, at least 19 loci have multiple independently associated variants, suggesting that allelic heterogeneity is a frequent feature of polygenic traits, that comprehensive explorations of already-discovered loci should discover additional variants and that an appreciable fraction of associated loci may have been identified. Fourth, associated variants are enriched for likely functional effects on genes, being over-represented among variants that alter amino-acid structure of proteins and expression levels of nearby genes. Our data explain approximately 10% of the phenotypic variation in height, and we estimate that unidentified common variants of similar effect sizes would increase this figure to approximately 16% of phenotypic variation (approximately 20% of heritable variation). Although additional approaches are needed to dissect the genetic architecture of polygenic human traits fully, our findings indicate that GWA studies can identify large numbers of loci that implicate biologically relevant genes and pathways.
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| 4. |
- Teslovich, Tanya M., et al.
(författare)
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Biological, clinical and population relevance of 95 loci for blood lipids
- 2010
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 466:7307, s. 707-713
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Tidskriftsartikel (refereegranskat)abstract
- Plasma concentrations of total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol and triglycerides are among the most important risk factors for coronary artery disease (CAD) and are targets for therapeutic intervention. We screened the genome for common variants associated with plasma lipids in >100,000 individuals of European ancestry. Here we report 95 significantly associated loci (P<5 x 10(-8)), with 59 showing genome-wide significant association with lipid traits for the first time. The newly reported associations include single nucleotide polymorphisms (SNPs) near known lipid regulators (for example, CYP7A1, NPC1L1 and SCARB1) as well as in scores of loci not previously implicated in lipoprotein metabolism. The 95 loci contribute not only to normal variation in lipid traits but also to extreme lipid phenotypes and have an impact on lipid traits in three non-European populations (East Asians, South Asians and African Americans). Our results identify several novel loci associated with plasma lipids that are also associated with CAD. Finally, we validated three of the novel genes-GALNT2, PPP1R3B and TTC39B-with experiments in mouse models. Taken together, our findings provide the foundation to develop a broader biological understanding of lipoprotein metabolism and to identify new therapeutic opportunities for the prevention of CAD.
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| 5. |
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| 6. |
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| 7. |
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| 8. |
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| 9. |
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| 10. |
- Palmer, Nicholette D, et al.
(författare)
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A genome-wide association search for type 2 diabetes genes in African Americans.
- 2012
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Ingår i: PloS one. - San Francisco : Public Library of Science (PLoS). - 1932-6203. ; 7:1, s. e29202-
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Tidskriftsartikel (refereegranskat)abstract
- African Americans are disproportionately affected by type 2 diabetes (T2DM) yet few studies have examined T2DM using genome-wide association approaches in this ethnicity. The aim of this study was to identify genes associated with T2DM in the African American population. We performed a Genome Wide Association Study (GWAS) using the Affymetrix 6.0 array in 965 African-American cases with T2DM and end-stage renal disease (T2DM-ESRD) and 1029 population-based controls. The most significant SNPs (n = 550 independent loci) were genotyped in a replication cohort and 122 SNPs (n = 98 independent loci) were further tested through genotyping three additional validation cohorts followed by meta-analysis in all five cohorts totaling 3,132 cases and 3,317 controls. Twelve SNPs had evidence of association in the GWAS (P<0.0071), were directionally consistent in the Replication cohort and were associated with T2DM in subjects without nephropathy (P<0.05). Meta-analysis in all cases and controls revealed a single SNP reaching genome-wide significance (P<2.5×10(-8)). SNP rs7560163 (P = 7.0×10(-9), OR (95% CI) = 0.75 (0.67-0.84)) is located intergenically between RND3 and RBM43. Four additional loci (rs7542900, rs4659485, rs2722769 and rs7107217) were associated with T2DM (P<0.05) and reached more nominal levels of significance (P<2.5×10(-5)) in the overall analysis and may represent novel loci that contribute to T2DM. We have identified novel T2DM-susceptibility variants in the African-American population. Notably, T2DM risk was associated with the major allele and implies an interesting genetic architecture in this population. These results suggest that multiple loci underlie T2DM susceptibility in the African-American population and that these loci are distinct from those identified in other ethnic populations.
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| 11. |
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| 12. |
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| 13. |
- Speliotes, Elizabeth K., et al.
(författare)
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Association analyses of 249,796 individuals reveal 18 new loci associated with body mass index
- 2010
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 42:11, s. 937-948
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Tidskriftsartikel (refereegranskat)abstract
- Obesity is globally prevalent and highly heritable, but its underlying genetic factors remain largely elusive. To identify genetic loci for obesity susceptibility, we examined associations between body mass index and ~2.8 million SNPs in up to 123,865 individuals with targeted follow up of 42 SNPs in up to 125,931 additional individuals. We confirmed 14 known obesity susceptibility loci and identified 18 new loci associated with body mass index (P < 5 × 10−8), one of which includes a copy number variant near GPRC5B. Some loci (at MC4R, POMC, SH2B1 and BDNF) map near key hypothalamic regulators of energy balance, and one of these loci is near GIPR, an incretin receptor. Furthermore, genes in other newly associated loci may provide new insights into human body weight regulation.
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| 14. |
- Heid, Iris M, et al.
(författare)
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Meta-analysis identifies 13 new loci associated with waist-hip ratio and reveals sexual dimorphism in the genetic basis of fat distribution
- 2010
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 42:11, s. 949-960
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Tidskriftsartikel (refereegranskat)abstract
- Waist-hip ratio (WHR) is a measure of body fat distribution and a predictor of metabolic consequences independent of overall adiposity. WHR is heritable, but few genetic variants influencing this trait have been identified. We conducted a meta-analysis of 32 genome-wide association studies for WHR adjusted for body mass index (comprising up to 77,167 participants), following up 16 loci in an additional 29 studies (comprising up to 113,636 subjects). We identified 13 new loci in or near RSPO3, VEGFA, TBX15-WARS2, NFE2L3, GRB14, DNM3-PIGC, ITPR2-SSPN, LY86, HOXC13, ADAMTS9, ZNRF3-KREMEN1, NISCH-STAB1 and CPEB4 (P = 1.9 × 10⁻⁹ to P = 1.8 × 10⁻⁴⁰) and the known signal at LYPLAL1. Seven of these loci exhibited marked sexual dimorphism, all with a stronger effect on WHR in women than men (P for sex difference = 1.9 × 10⁻³ to P = 1.2 × 10⁻¹³). These findings provide evidence for multiple loci that modulate body fat distribution independent of overall adiposity and reveal strong gene-by-sex interactions.
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| 15. |
- Barrett, Jennifer H., et al.
(författare)
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Genome-wide association study identifies three new melanoma susceptibility loci
- 2011
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 43:11, s. 1108-1113
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Tidskriftsartikel (refereegranskat)abstract
- We report a genome-wide association study for melanoma that was conducted by the GenoMEL Consortium. Our discovery phase included 2,981 individuals with melanoma and 1,982 study-specific control individuals of European ancestry, as well as an additional 6,426 control subjects from French or British populations, all of whom were genotyped for 317,000 or 610,000 single-nucleotide polymorphisms (SNPs). Our analysis replicated previously known melanoma susceptibility loci. Seven new regions with at least one SNP with P < 10(-5) and further local imputed or genotyped support were selected for replication using two other genome-wide studies (from Australia and Texas, USA). Additional replication came from case-control series from the UK and The Netherlands. Variants at three of the seven loci replicated at P < 10(-3): an SNP in ATM (rs1801516, overall P = 3.4 x 10(-9)), an SNP in MX2 (rs45430, P = 2.9 x 10-9) and an SNP adjacent to CASP8 (rs13016963, P = 8.6 x 10(-10)). A fourth locus near CCND1 remains of potential interest, showing suggestive but inconclusive evidence of replication (rs1485993, overall P = 4.6 x 10(-7) under a fixed-effects model and P = 1.2 x 10(-3) under a random-effects model). These newly associated variants showed no association with nevus or pigmentation phenotypes in a large British case-control series.
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| 16. |
- Engel, C., et al.
(författare)
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Association of the variants CASP8 D302H and CASP10 V410I with breast and ovarian cancer risk in BRCA1 and BRCA2 mutation carriers
- 2010
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Ingår i: Cancer Epidemiology, Biomarkers and Prevention. - : American Association for Cancer Research. - 1055-9965 .- 1538-7755. ; 19:11, s. 2859-2868
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Tidskriftsartikel (refereegranskat)abstract
- Background: The genes caspase-8 (CASP8) and caspase-10 (CASP10) functionally cooperate and play a key role in the initiation of apoptosis. Suppression of apoptosis is one of the major mechanisms underlying the origin and progression of cancer. Previous case-control studies have indicated that the polymorphisms CASP8 D302H and CASP10 V410I are associated with a reduced risk of breast cancer in the general population.Methods: To evaluate whether the CASP8 D302H (CASP10 V410I) polymorphisms modify breast or ovarian cancer risk in BRCA1 and BRCA2 mutation carriers, we analyzed 7,353 (7,227) subjects of white European origin provided by 19 (18) study groups that participate in the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). A weighted cohort approach was used to estimate hazard ratios (HR) and 95% confidence intervals (95% CI).Results: The minor allele of CASP8 D302H was significantly associated with a reduced risk of breast cancer (per-allele HR, 0.85; 95% CI, 0.76-0.97; Ptrend = 0.011) and ovarian cancer (per-allele HR, 0.69; 95% CI, 0.53-0.89; Ptrend = 0.004) for BRCA1 but not for BRCA2 mutation carriers. The CASP10 V410I polymorphism was not associated with breast or ovarian cancer risk for BRCA1 or BRCA2 mutation carriers.Conclusions: CASP8 D302H decreases breast and ovarian cancer risk for BRCA1 mutation carriers but not for BRCA2 mutation carriers.Impact: The combined application of these and other recently identified genetic riskmodifiers could in the future allow better individual risk calculation and could aid in the individualized counseling and decision making with respect to preventive options in BRCA1 mutation carriers.
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| 17. |
- Hoare, M. G., et al.
(författare)
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The cradle of life and the SKA
- 2014
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Ingår i: Proceedings of Science. - 1824-8039. ; 9-13-June-2014
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Konferensbidrag (refereegranskat)abstract
- We provide an overview of the exciting capabilities of the SKA in the Cradle of Life theme. With the deployment of the high frequency band 5 receivers, the phase 1 of the SKA can conduct headline science in the study of the earliest stages of grain growth in proto-planetary disks. SKA1-MID can map the 2 cm continuum emission at a resolution of 4 au in the nearest systems and therefore begin to probe the distribuion of cm-sized particles across the snow line. This frequency range will also enable deep searches for pre-biotic molecules such as amino acids from pre-stellar cores to the cold, outer regions of proto-planetary disks where cometary material forms. The lowest frequency capabilities of SKA1 can be used to examine the magnetic fields of exo-planets via their auroral radio emission. This gives unique insight into their interiors and could potentially detect exo-moons. Across the full frequency range, the SKA1 will also carry out systematic, volume-limited searches of exo-planet systems for signals from technologically advanced civilizations. The sensitivity of SKA1 means that these only need to be at the level of typical airport radar signals in the nearest systems. Hence, the SKA1 can conduct high impact science from the first steps on the road to planets and life, through areas affecting the habitability of planets, and ultimately, to whether we are alone in the Galaxy. These inspirational themes will greatly help in the effort to bring SKA1 science to a wide audience and to ensure the progression to the full SKA.
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| 18. |
- Mann, G. W., et al.
(författare)
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Intercomparison and evaluation of global aerosol microphysical properties among AeroCom models of a range of complexity
- 2014
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Ingår i: Atmospheric Chemistry And Physics. - : Copernicus GmbH. - 1680-7316 .- 1680-7324. ; 14:9, s. 4679-4713
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Tidskriftsartikel (refereegranskat)abstract
- Many of the next generation of global climate models will include aerosol schemes which explicitly simulate the microphysical processes that determine the particle size distribution. These models enable aerosol optical properties and cloud condensation nuclei (CCN) concentrations to be determined by fundamental aerosol processes, which should lead to a more physically based simulation of aerosol direct and indirect radiative forcings. This study examines the global variation in particle size distribution simulated by 12 global aerosol microphysics models to quantify model diversity and to identify any common biases against observations. Evaluation against size distribution measurements from a new European network of aerosol supersites shows that the mean model agrees quite well with the observations at many sites on the annual mean, but there are some seasonal biases common to many sites. In particular, at many of these European sites, the accumulation mode number concentration is biased low during winter and Aitken mode concentrations tend to be overestimated in winter and underestimated in summer. At high northern latitudes, the models strongly underpredict Aitken and accumulation particle concentrations compared to the measurements, consistent with previous studies that have highlighted the poor performance of global aerosol models in the Arctic. In the marine boundary layer, the models capture the observed meridional variation in the size distribution, which is dominated by the Aitken mode at high latitudes, with an increasing concentration of accumulation particles with decreasing latitude. Considering vertical profiles, the models reproduce the observed peak in total particle concentrations in the upper troposphere due to new particle formation, although modelled peak concentrations tend to be biased high over Europe. Overall, the multimodel-mean data set simulates the global variation of the particle size distribution with a good degree of skill, suggesting that most of the individual global aerosol microphysics models are performing well, although the large model diversity indicates that some models are in poor agreement with the observations. Further work is required to better constrain size-resolved primary and secondary particle number sources, and an improved understanding of nucleation and growth (e. g. the role of nitrate and secondary organics) will improve the fidelity of simulated particle size distributions.
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| 19. |
- Naranjo, A., et al.
(författare)
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Smokers and non-smokers with rheumatoid arthritis have similar clinical status : data from the multinational QUEST-RA database
- 2010
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Ingår i: Clinical and Experimental Rheumatology. - 0392-856X .- 1593-098X. ; 28:6, s. 820-827
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Tidskriftsartikel (refereegranskat)abstract
- Objectives To analyse clinical severity/activity of rheumatoid arthritis (RA) according to smoking status. Methods The QUEST-RA multinational database reviews patients for Core Data Set measures including 28 swollen and tender joint count, physician global estimate, erythrocyte sedimentation rate (ESR), HAQ-function, pain, and patient global estimate, as well as DAS28, rheumatoid factor (RE), nodules, erosions and number of DMARDs were recorded. Smoking status was assessed by self-report as "never smoked", "currently smoking" and "former smokers". Patient groups with different smoking status were compared for demographic and RA measures. Results Among the 7,307 patients with smoking data available, status as "never smoked," "current smoker" and "former smoker" were reported by 65%, 15% and 20%. Ever smokers were more likely to be RF-positive (OR 1.32; 1.17-1.48, p<0.001). Rheumatoid nodules were more frequent in ever smokers (OR 1.41; 1.24-1.59, p<0.001). The percentage of patients with erosive arthritis and extra-articular disease was similar in all smoking categories. Mean DAS28 was 4.4 (SD 1.6) in non-smokers vs. 4.0 (SD 1.6) in those who had ever smoked. However, when adjusted by age, sex, disease duration, and country gross domestic product, only ESR remained significantly different among Core Data Set measures (mean 31.7mm in non-smokers vs. 26.8mm in ever smoked category). Conclusion RA patients who had ever smoked were more likely to have RF and nodules, hut values for other clinical status measures were similar in all smoking categories (never smoked, current smokers and former smokers).
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| 20. |
- Scott, Robert A., et al.
(författare)
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Large-scale association analyses identify new loci influencing glycemic traits and provide insight into the underlying biological pathways
- 2012
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 44:9, s. 991-1005
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Tidskriftsartikel (refereegranskat)abstract
- Through genome-wide association meta-analyses of up to 133,010 individuals of European ancestry without diabetes, including individuals newly genotyped using the Metabochip, we have increased the number of confirmed loci influencing glycemic traits to 53, of which 33 also increase type 2 diabetes risk (q < 0.05). Loci influencing fasting insulin concentration showed association with lipid levels and fat distribution, suggesting impact on insulin resistance. Gene-based analyses identified further biologically plausible loci, suggesting that additional loci beyond those reaching genome-wide significance are likely to represent real associations. This conclusion is supported by an excess of directionally consistent and nominally significant signals between discovery and follow-up studies. Functional analysis of these newly discovered loci will further improve our understanding of glycemic control.
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| 21. |
- Bjerkeli, Per, 1977, et al.
(författare)
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H2O line mapping at high spatial and spectral resolution Herschel observations of the VLA 1623 outflow
- 2012
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 546, s. Article Number: A29 -
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Tidskriftsartikel (refereegranskat)abstract
- Context. Apart from being an important coolant, water is known to be a tracer of high-velocity molecular gas. Recent models predict relatively high abundances behind interstellar shockwaves. The dynamical and physical conditions of the water emitting gas, however, are not fully understood yet. Using the Herschel Space Observatory, it is now possible to observe water emission from supersonic molecular outflows at high spectral and spatial resolution. Several molecular outflows from young stars are currently being observed as part of the WISH (Water In Star-forming regions with Herschel) key program. Aims. We aim to determine the abundance and distribution of water, its kinematics, and the physical conditions of the gas responsible for the water emission. The observed line profile shapes help us understand the dynamics in molecular outflows. Methods. We mapped the VLA1623 outflow, in the ground-state transitions of o-H2O, with the HIFI and PACS instruments. We also present observations of higher energy transitions of o-H2O and p-H2O obtained with HIFI and PACS towards selected outflow positions. From comparison with non-LTE radiative transfer calculations, we estimate the physical parameters of the water emitting regions. Results. The observed water emission line profiles vary over the mapped area. Spectral features and components, tracing gas in different excitation conditions, allow us to constrain the density and temperature of the gas. The water emission originates in a region where temperatures are comparable to that of the warm H-2 gas (T greater than or similar to 200 K). Thus, the water emission traces a gas component significantly warmer than the gas responsible for the low-J CO emission. The water column densities at the CO peak positions are low, i.e. N(H2O) similar or equal to (0.03-10) x 10(14) cm(-2). Conclusions. The water abundance with respect to H-2 in the extended outflow is estimated at X(H2O)
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| 22. |
- Demenais, F, et al.
(författare)
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Association of MC1R Variants and Host Phenotypes With Melanoma Risk in CDKN2A Mutation Carriers: A GenoMEL Study.
- 2010
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Ingår i: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 1460-2105 .- 0027-8874. ; 102, s. 1568-1583
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Tidskriftsartikel (refereegranskat)abstract
- Background Carrying the cyclin-dependent kinase inhibitor 2A (CDKN2A) germline mutations is associated with a high risk for melanoma. Penetrance of CDKN2A mutations is modified by pigmentation characteristics, nevus phenotypes, and some variants of the melanocortin-1 receptor gene (MC1R), which is known to have a role in the pigmentation process. However, investigation of the associations of both MC1R variants and host phenotypes with melanoma risk has been limited. Methods We included 815 CDKN2A mutation carriers (473 affected, and 342 unaffected, with melanoma) from 186 families from 15 centers in Europe, North America, and Australia who participated in the Melanoma Genetics Consortium. In this family-based study, we assessed the associations of the four most frequent MC1R variants (V60L, V92M, R151C, and R160W) and the number of variants (1, ≥2 variants), alone or jointly with the host phenotypes (hair color, propensity to sunburn, and number of nevi), with melanoma risk in CDKN2A mutation carriers. These associations were estimated and tested using generalized estimating equations. All statistical tests were two-sided. Results Carrying any one of the four most frequent MC1R variants (V60L, V92M, R151C, R160W) in CDKN2A mutation carriers was associated with a statistically significantly increased risk for melanoma across all continents (1.24 × 10(-6) ≤ P ≤ .0007). A consistent pattern of increase in melanoma risk was also associated with increase in number of MC1R variants. The risk of melanoma associated with at least two MC1R variants was 2.6-fold higher than the risk associated with only one variant (odds ratio = 5.83 [95% confidence interval = 3.60 to 9.46] vs 2.25 [95% confidence interval = 1.44 to 3.52]; P(trend) = 1.86 × 10(-8)). The joint analysis of MC1R variants and host phenotypes showed statistically significant associations of melanoma risk, together with MC1R variants (.0001 ≤ P ≤ .04), hair color (.006 ≤ P ≤ .06), and number of nevi (6.9 × 10(-6) ≤ P ≤ .02). Conclusion Results show that MC1R variants, hair color, and number of nevi were jointly associated with melanoma risk in CDKN2A mutation carriers. This joint association may have important consequences for risk assessments in familial settings.
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| 23. |
- Gron, K. L., et al.
(författare)
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The association of fatigue, comorbidity burden, disease activity, disability and gross domestic product in patients with rheumatoid arthritis. : Results from 34 countries participating in the Quest-RA programme
- 2014
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Ingår i: Clinical and Experimental Rheumatology. - 0392-856X .- 1593-098X. ; 32:6, s. 869-877
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Tidskriftsartikel (refereegranskat)abstract
- Objective The aim is to assess the prevalence of comorbidities and to further analyse to which degree fatigue can be explained by comorbidity burden, disease activity, disability and gross domestic product (GDP) in patients with rheumatoid arthritis (RA). Methods Nine thousands eight hundred seventy-four patients from 34 countries, 16 with high GDP (>24.000 US dollars [USD] per capita) and 18 low-GDP countries (<24.000 USD) participated in the Quantitative Standard monitoring of Patients with RA (QUEST-RA) study. The prevalence of 31 comorbid conditions, fatigue (0-10 cm visual analogue scale [VAS] [10 worst]), disease activity in 28 joints (DAS28), and physical disability (Health Assessment Questionnaire score MAW) were assessed. Univariate and multivariate linear regression analyses were performed to assess the association between fatigue and comorbidities, disease activity, disability and GDP. Results Overall, patients reported a median of 2 comorbid conditions of which hypertension (31.5%), osteoporosis (17.6%), osteoarthritis (15.5%) and hyperlipidaemia (14.2%) were the most prevalent. The majority of comorbidities were more common in high-GDP countries. The median fatigue score was 4.4 (4.8 in low-GDP countries and 3.8 in high-GDP countries, p<0.001). In low-GDP countries 25.4% of the patients had a high level of fatigue (>6.6) compared with 23.0% in high-GDP countries (p<0.001). In univariate analysis, fatigue increased with increasing number of comorbidities, disease activity and disability in both high- and low-GDP countries. In multivariate analysis of all countries, these 3 variables explained 29.4% of the variability, whereas GDP was not significant. Conclusion Fatigue is a widespread problem associated with high comorbidity burden, disease activity and disability regardless of GDP.
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| 24. |
- Herbschleb, C. T., et al.
(författare)
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The ReactorSTM : Atomically resolved scanning tunneling microscopy under high-pressure, high-temperature catalytic reaction conditions
- 2014
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Ingår i: Review of Scientific Instruments. - : AIP Publishing. - 0034-6748 .- 1089-7623. ; 85:8
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Tidskriftsartikel (refereegranskat)abstract
- To enable atomic-scale observations of model catalysts under conditions approaching those used by the chemical industry, we have developed a second generation, high-pressure, high-temperature scanning tunneling microscope (STM): the ReactorSTM. It consists of a compact STM scanner, of which the tip extends into a 0.5 ml reactor flow-cell, that is housed in a ultra-high vacuum (UHV) system. The STM can be operated from UHV to 6 bars and from room temperature up to 600 K. A gas mixing and analysis system optimized for fast response times allows us to directly correlate the surface structure observed by STM with reactivity measurements from a mass spectrometer. The in situ STM experiments can be combined with ex situ UHV sample preparation and analysis techniques, including ion bombardment, thin film deposition, low-energy electron diffraction and x-ray photoelectron spectroscopy. The performance of the instrument is demonstrated by atomically resolved images of Au(111) and atom-row resolution on Pt(110), both under high-pressure and high-temperature conditions.
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| 25. |
- Iles, Mark M., et al.
(författare)
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A variant in FTO shows association with melanoma risk not due to BMI
- 2013
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 45:4, s. 428-432
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Tidskriftsartikel (refereegranskat)abstract
- We report the results of an association study of melanoma that is based on the genome-wide imputation of the genotypes of 1,353 cases and 3,566 controls of European origin conducted by the GenoMEL consortium. This revealed an association between several SNPs in intron 8 of the FTO gene, including rs16953002, which replicated using 12,313 cases and 55,667 controls of European ancestry from Europe, the USA and Australia (combined P = 3.6 x 10(-12), per-allele odds ratio for allele A = 1.16). In addition to identifying a new melanomasusceptibility locus, this is to our knowledge the first study to identify and replicate an association with SNPs in FTO not related to body mass index (BMI). These SNPs are not in intron 1 (the BMI-related region) and exhibit no association with BMI. This suggests FTO's function may be broader than the existing paradigm that FTO variants influence multiple traits only through their associations with BMI and obesity.
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| 26. |
- Lundgren, A., et al.
(författare)
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APEX: Five years of operations
- 2010
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Ingår i: Proceedings of SPIE - The International Society for Optical Engineering. - : SPIE. - 0277-786X .- 1996-756X. - 9780819482273 ; 7737
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- APEX, the Atacama Pathfinder EXperiment, is being operated successfully, now for five years, on Llano de Chajnantor at 5107m altitude in the Chilean High Andes. This location is considered one of the worlds outstanding sites for submillimeter astronomy, which the results described in this contribution are underlining. The primary reflector with 12 m diameter is cautiously being maintained at about 15 μm by means of holography. This allows to access all atmospheric submillimeter windows accessible from the ground, up to 200 μm. Telescope and instrument performance, operational experiences and a selection of scientific results are given in this publication. © 2010 Copyright SPIE - The International Society for Optical Engineering.
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| 27. |
- Nyqvist, Kerstin Hedberg, et al.
(författare)
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State of the art and recommendations. Kangaroo mother care : application in a high-tech environment
- 2010
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Ingår i: Acta Paediatrica. - : Wiley. - 0803-5253 .- 1651-2227. ; 18:3, s. 21-28
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Tidskriftsartikel (refereegranskat)abstract
- Since Kangaroo Mother Care (KMC) was developed in Colombia in the 1970s, two trends in clinical application emerged. In low income settings, the original KMC model is implemented. This consists of continuous (24 h/day, 7 days/week) and prolonged mother/parent-infant skin-to-skin contact; early discharge with the infant in the kangaroo position; (ideally) exclusive breastfeeding; and, adequate follow-up. In affluent settings, intermittent KMC with sessions of one or a few hours skin-to-skin contact for a limited period is common. As a result of the increasing evidence of the benefits of KMC for both infants and families in all intensive care settings, KMC in a high-tech environment was chosen as the topic for the first European Conference on KMC, and the clinical implementation of the KMC model in all types of settings was discussed at the 7th International Workshop on KMC. Kangaroo Mother Care protocols in high-tech Neonatal Intensive Care Units (NICU) should specify criteria for initiation, kangaroo position, transfer to/from KMC, transport in kangaroo position, kangaroo nutrition, parents' role, modification of the NICU environment, performance of care in KMC, and KMC in case of infant instability. Conclusion: Implementation of the original KMC method, with continuous skin-to-skin contact whenever possible, is recommended for application in high-tech environments, although scientific evaluation should continue.
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| 28. |
- Nyqvist, Kerstin Hedberg, et al.
(författare)
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Towards universal Kangaroo Mother Care : recommendations and report from the First European conference and Seventh International Workshop on Kangaroo Mother Care
- 2010
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Ingår i: Acta Paediatrica. - : Wiley. - 0803-5253 .- 1651-2227. ; 99:6, s. 820-826
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Tidskriftsartikel (refereegranskat)abstract
- The hallmark of Kangaroo Mother Care (KMC) is the kangaroo position: the infant is cared for skin-to-skin vertically between the mother's breasts and below her clothes, 24 h/day, with father/substitute(s) participating as KMC providers. Intermittent KMC (for short periods once or a few times per day, for a variable number of days) is commonly employed in high-tech neonatal intensive care units. These two modalities should be regarded as a progressive adaptation of the mother-infant dyad, ideally towards continuous KMC, starting gradually and progressively with intermittent KMC. The other components in KMC are exclusive breastfeeding (ideally) and early discharge in kangaroo position with strict follow-up. Current evidence allows the following general statements about KMC in affluent and low-income settings: KMC enhances bonding and attachment; reduces maternal postpartum depression symptoms; enhances infant physiologic stability and reduces pain, increases parental sensitivity to infant cues; contributes to the establishment and longer duration of breastfeeding and has positive effects on infant development and infant/parent interaction. Therefore, intrapartum and postnatal care in all types of settings should adhere to a paradigm of nonseparation of infants and their mothers/families. Preterm/low-birth-weight infants should be regarded as extero-gestational foetuses needing skin-to-skin contact to promote maturation. Conclusion: Kangaroo Mother Care should begin as soon as possible after birth, be applied as continuous skin-to-skin contact to the extent that this is possible and appropriate and continue for as long as appropriate.
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| 29. |
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| 30. |
- Yaghootkar, Hanieh, et al.
(författare)
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Mendelian randomization studies do not support a causal role for reduced circulating adiponectin levels in insulin resistance and type 2 diabetes.
- 2013
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Ingår i: Diabetes. - : American Diabetes Association. - 1939-327X .- 0012-1797. ; 62:10, s. 3589-3598
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Tidskriftsartikel (refereegranskat)abstract
- Adiponectin is strongly inversely associated with insulin resistance and type 2 diabetes, but its causal role remains controversial. We used a Mendelian randomization approach to test the hypothesis that adiponectin causally influences insulin resistance and type 2 diabetes. We used genetic variants at the ADIPOQ gene as instruments to calculate a regression slope between adiponectin levels and metabolic traits (up to 31,000 individuals) and a combination of instrumental variables and summary statistics-based genetic risk scores to test the associations with gold-standard measures of insulin sensitivity (2,969 individuals) and type 2 diabetes (15,960 case subjects and 64,731 control subjects). In conventional regression analyses, a 1-SD decrease in adiponectin levels was correlated with a 0.31-SD (95% CI 0.26-0.35) increase in fasting insulin, a 0.34-SD (0.30-0.38) decrease in insulin sensitivity, and a type 2 diabetes odds ratio (OR) of 1.75 (1.47-2.13). The instrumental variable analysis revealed no evidence of a causal association between genetically lower circulating adiponectin and higher fasting insulin (0.02 SD; 95% CI -0.07 to 0.11; N = 29,771), nominal evidence of a causal relationship with lower insulin sensitivity (-0.20 SD; 95% CI -0.38 to -0.02; N = 1,860), and no evidence of a relationship with type 2 diabetes (OR 0.94; 95% CI 0.75-1.19; N = 2,777 case subjects and 13,011 control subjects). Using the ADIPOQ summary statistics genetic risk scores, we found no evidence of an association between adiponectin-lowering alleles and insulin sensitivity (effect per weighted adiponectin-lowering allele: -0.03 SD; 95% CI -0.07 to 0.01; N = 2,969) or type 2 diabetes (OR per weighted adiponectin-lowering allele: 0.99; 95% CI 0.95-1.04; 15,960 case subjects vs. 64,731 control subjects). These results do not provide any consistent evidence that interventions aimed at increasing adiponectin levels will improve insulin sensitivity or risk of type 2 diabetes.
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| 31. |
- Andersson, G., et al.
(författare)
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Psychological treatments for depression delivered via the internet and supported by a clinician: An pdate : [Tratamientos psicológicos para la depresión aplicados a través de Internet y con el apoyo de un clínico: Una actualización]
- 2014
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Ingår i: Revista de Psicopatologia y Psicologia Clinica. - : Asociación de Análisis del Comportamiento. - 1136-5420 .- 2254-6057. ; 19:3, s. 217-225
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Forskningsöversikt (refereegranskat)abstract
- Guided internet-delivered cognitive behaviour therapy (ICBT) has been tested in many trials since the early studies dating back to the late 1990s. The aim of this review was to investigate the most recent literature on guided ICBT for depression. We identified 11 controlled studies published between January 2013 and September 2014. Overall, large treatment effects were observed with a few exceptions. A majority (7 studies) provided some information regarding unwanted effects such as deterioration. Three studies directly compared guided ICBT against face-to-face CBT. We added an earlier study and calculated meta-analytic summary statistics for the four studies involving a total of 336 participants. The average effect size difference was Hedges g = 0.12 (95% CI: -0.08∼0.32) in the direction of favouring guided ICBT, but with no practical importance. We conclude that guided ICBT is a promising treatment for depression and mood disorders and that the research is rapidly expanding.
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| 32. |
- Bergman, Anders, et al.
(författare)
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Metrology for high voltage direct current
- 2010
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Ingår i: CPEM Digest (Conference on Precision Electromagnetic Measurements). - 9781424467952 ; , s. 669-670
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Konferensbidrag (refereegranskat)abstract
- HVDC energy transmission is crucial for a successful uptake of renewable energy sources in the grid. A research program is described, intended to provide metrology support for the needs of HVDC energy transmission. This program will provide improvements for the present HVDC metrology infrastructure: accurate measurement of HVDC, determination of losses in HVDC systems, on-site power quality measurements at HVDC substations, and DC metering. It is a combined effort of 7 European national metrology institutes, one university and one industrial partner. © 2010 IEEE.
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| 37. |
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| 38. |
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| 39. |
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| 40. |
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| 41. |
- Bjerkeli, Per, 1977, et al.
(författare)
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Herschel observations of the Herbig-Haro objects HH52-54
- 2011
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 533
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Tidskriftsartikel (refereegranskat)abstract
- Context. The emission from Herbig-Haro objects and supersonic molecular outflows is understood as cooling radiation behind shocks, which are initiated by a (proto-)stellar wind or jet. Within a given object, one often observes both dissociative (J-type) and non-dissociative (C-type) shocks, owing to the collective effects of internally varying shock velocities. Aims. We aim at the observational estimation of the relative contribution to the cooling by CO and H(2)O, as this provides decisive information for understanding the oxygen chemistry behind interstellar shock waves. Methods. The high sensitivity of HIFI, in combination with its high spectral resolution capability, allowed us to trace the H(2)O outflow wings at an unprecedented signal-to-noise ratio. From the observation of spectrally resolved H(2)O and CO lines in the HH52-54 system, both from space and from the ground, we arrived at the spatial and velocity distribution of the molecular outflow gas. Solving the statistical equilibrium and non-LTE radiative transfer equations provides us with estimates of the physical parameters of this gas, including the cooling rate ratios of the species. The radiative transfer is based on an accelerated lambda iteration code, where we use the fact that variable shock strengths, distributed along the front, are naturally implied by a curved surface. Results. Based on observations of CO and H(2)O spectral lines, we conclude that the emission is confined to the HH54 region. The quantitative analysis of our observations favours a ratio of the CO-to-H(2)O-cooling-rate >> 1. Formally, we derived the ratio A(CO)/A(o-H(2)O) = 10, which is in good agreement with earlier determination of 7 based on ISO-LWS observations. From the best-fit model to the CO emission, we arrive at an H(2)O abundance close to 1 x 10(-5). The line profiles exhibit two components, one that is triangular and another that is a superposed, additional feature. This additional feature is likely to find its origin in a region that is smaller than the beam where the ortho-water abundance is smaller than in the quiescent gas. Conclusions. Comparison with recent shock models indicate that a planar shock cannot easily explain the observed line strengths and triangular line profiles. We conclude that the geometry can play an important role. Although abundances support a scenario where J-type shocks are present, higher cooling rate ratios are derived than predicted by these types of shocks.
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| 42. |
- Bjerkeli, Per, 1977, et al.
(författare)
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Physical properties of outflows Comparing CO- and H2O-based parameters in Class 0 sources
- 2013
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 552
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Tidskriftsartikel (refereegranskat)abstract
- Context. The observed physical properties of outflows from low-mass sources put constraints on possible ejection mechanisms. Historically, these quantities have been derived from CO using ground-based observations. It is, therefore, important to investigate whether parameters such as momentum rate (thrust) and mechanical luminosity (power) are the same when different molecular tracers are used.Aims. Our objective is to determine the outflow momentum, dynamical time-scale, thrust, energy, and power using CO and H2O as tracers of outflow activity.Methods. Within the framework of the Water In Star-forming regions with Herschel (WISH) key program, three molecular outflows from Class 0 sources have been mapped using the Heterodyne Instrument for the Far Infrared (HIFI) instrument aboard Herschel. We used these observations together with previously published H-2 data to infer the physical properties of the outflows. We compared the physical properties derived here with previous estimates based on CO observations.Results. Inspection of the spatial distribution of H2O and H-2 confirms that these molecules are co-spatial. The most prominent emission peaks in H-2 coincide with strong H2O emission peaks and the estimated widths of the flows when using the two tracers are comparable.Conclusions. For the momentum rate and the mechanical luminosity, inferred values are not dependent on which tracer is used, i.e. the values agree to within a factor of 4 and 3, respectively.
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| 43. |
- Bremander, Ann, et al.
(författare)
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Depression and age as predictors of patient-reported outcome in a multidisciplinary rehabilitation programme for chronic musculoskeletal pain.
- 2011
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Ingår i: Musculoskeletal Care. - : Wiley. - 1557-0681 .- 1478-2189. ; 9:1, s. 8-41
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Tidskriftsartikel (refereegranskat)abstract
- Background. The recommended treatment for chronic musculoskeletal pain is multidisciplinary, with a cognitive approach. The aim of this study was to investigate health-related quality of life (HRQoL) outcome after a multidisciplinary treatment with a cognitive approach. Methods. A total of 131 subjects who participated in a multidisciplinary rehabilitation programme (2005-2008) were studied at baseline and after six months, using the Short Form Short Form 36-item Health Survey questionnaire (SF-36) as primary outcome (HRQoL), and the Hospital Anxiety and Depression Scale (HAD) and pain as secondary outcomes and possible baseline predictors for HRQoL. Results. Complete data were available for 97 subjects (85 women, mean age [SD] 44.6 [9.7] years). The SF-36 subscales physical function (PF), general health (GH), vitality (VT), social function (SF) and mental health (MH), the visual analogue scale for pain and the HAD improved significantly (p < 0.05) at follow-up compared with baseline. A pre-treatment probable depression (HAD score ≥11) was associated with a favourable outcome of the SF-36 subscales PF (odds ratio [OR] 5.6; p = 0.01), VT (OR 4.3; p = 0.02) and MH (OR 3.6; p = 0.02). A probable anxiety (HAD score ≥11) was associated with a favourable outcome of PF (OR 2.6; p = 0.05). There was an even stronger association for younger subjects (20-45 years), with probable depression scores at baseline and a favourable HRQoL outcome at follow up. Conclusion. This multidisciplinary rehabilitation programme, using a non-pharmacological cognitive approach, seemed to yield a better outcome concerning HRQoL measures in younger subjects with higher depression scores at baseline. This information is important for clinics when tailoring a multidisciplinary rehabilitation programme for patients with musculoskeletal chronic pain. Copyright © 2010 John Wiley & Sons, Ltd.
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| 44. |
- Claussen, M. J., et al.
(författare)
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A Pilot Imaging Line Survey of RW LMi and IK Tau Using the Expanded Very Large Array
- 2011
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Ingår i: Astrophysical Journal Letters. - 2041-8213 .- 2041-8205. ; 739:1, s. L5-
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Tidskriftsartikel (refereegranskat)abstract
- We report on a pilot imaging line survey (36.0-37.0 GHz, with ~1 km s–1 spectral channels) with the Expanded Very Large Array for two asymptotic giant branch stars, RW LMi (= CIT6, which has a carbon-rich circumstellar envelope, CSE) and IK Tau (=NML Tau, with an oxygen-rich CSE). Radio continuum emission consistent with photospheric emission was detected from both stars. From RW LMi we imaged the HC3N (J = 4→3) emission. The images show several partial rings of emission; these multiple shells trace the evolution of the CSE from 400 to 1200 years. SiS (J = 2→1) emission was detected from both RW LMi and IK Tau. For both stars the SiS emission is centrally condensed with the peak line emission coincident with the stellar radio continuum emission. In addition, we have detected weak HC7N (J = 32→31) emission from RW LMi.
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| 45. |
- De Vriendt, T., et al.
(författare)
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Reliability and validity of the Adolescent Stress Questionnaire in a sample of European adolescents--the HELENA study
- 2011
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Ingår i: BMC Public Health. - : Springer Science and Business Media LLC. - 1471-2458. ; 11, s. 717-
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Since stress is hypothesized to play a role in the etiology of obesity during adolescence, research on associations between adolescent stress and obesity-related parameters and behaviours is essential. Due to lack of a well-established recent stress checklist for use in European adolescents, the study investigated the reliability and validity of the Adolescent Stress Questionnaire (ASQ) for assessing perceived stress in European adolescents. METHODS: The ASQ was translated into the languages of the participating cities (Ghent, Stockholm, Vienna, Zaragoza, Pecs and Athens) and was implemented within the HELENA cross-sectional study. A total of 1140 European adolescents provided a valid ASQ, comprising 10 component scales, used for internal reliability (Cronbach alpha) and construct validity (confirmatory factor analysis or CFA). Contributions of socio-demographic (gender, age, pubertal stage, socio-economic status) characteristics to the ASQ score variances were investigated. Two-hundred adolescents also provided valid saliva samples for cortisol analysis to compare with the ASQ scores (criterion validity). Test-retest reliability was investigated using two ASQ assessments from 37 adolescents. RESULTS: Cronbach alpha-values of the ASQ scales (0.57 to 0.88) demonstrated a moderate internal reliability of the ASQ, and intraclass correlation coefficients (0.45 to 0.84) established an insufficient test-retest reliability of the ASQ. The adolescents' gender (girls had higher stress scores than boys) and pubertal stage (those in a post-pubertal development had higher stress scores than others) significantly contributed to the variance in ASQ scores, while their age and socio-economic status did not. CFA results showed that the original scale construct fitted moderately with the data in our European adolescent population. Only in boys, four out of 10 ASQ scale scores were a significant positive predictor for baseline wake-up salivary cortisol, suggesting a rather poor criterion validity of the ASQ, especially in girls. CONCLUSIONS: In our European adolescent sample, the ASQ had an acceptable internal reliability and construct validity and the adolescents' gender and pubertal stage systematically contributed to the ASQ variance, but its test-retest reliability and criterion validity were rather poor. Overall, the utility of the ASQ for assessing perceived stress in adolescents across Europe is uncertain and some aspects require further examination.
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| 46. |
- Edberg, Anna, et al.
(författare)
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Assessing Relative Bioactivity of Chemical Substances Using Quantitative Molecular Network Topology Analysis
- 2012
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Ingår i: Journal of Chemical Information and Modeling. - : American Chemical Society (ACS). - 1549-9596 .- 1549-960X. ; 52:5, s. 1238-1249
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Tidskriftsartikel (refereegranskat)abstract
- Structurally different chemical substances may cause similar systemic effects in mammalian cells. It is therefore necessary to go beyond structural comparisons to quantify similarity in terms of their bioactivities. In this work, we introduce a generic methodology to achieve this on the basis of Network Biology principles and using publicly available molecular network topology information. An implementation of this method, denoted QuantMap, is outlined and applied to antidiabetic drugs, NSAIDs, 17 beta-estradiol, and 12 substances known to disrupt estrogenic pathways. The similarity of any pair of compounds is derived from topological comparison of intracellular protein networks, directly and indirectly associated with the respective query chemicals, via a straightforward pairwise comparison of ranked proteins. Although output derived from straightforward chemical/structural similarity analysis provided some guidance on bioactivity, QuantMap produced substance interrelationships that align well with reports on their respective perturbation properties. We believe that QuantMap has potential to provide substantial assistance to drug repositioning, pharmacology evaluation, and toxicology risk assessment.
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| 47. |
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| 48. |
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| 49. |
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| 50. |
- Kullgren, Andreas, 1977, et al.
(författare)
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A metabolomics approach to elucidate effects of food deprivation in juvenile rainbow trout (Oncorhynchus mykiss)
- 2010
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Ingår i: American Journal of Physiology-Regulatory Integrative and Comparative Physiology. - : American Physiological Society. - 0363-6119 .- 1522-1490. ; 299:6
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to evaluate whether NMR-based metabolomics is a suitable method to generate an integrated view on metabolic processes during food deprivation in salmonid fish. Juvenile rainbow trout (Oncorhynchus mykiss) weighing 43-115 g were either fed ad libitum or deprived of food for 28 days at 10 degrees C to investigate catabolic effects on energy reserves and metabolite patterns. The NMR analysis of plasma, liver, and muscle extracts revealed significant fasting-induced changes in the metabolome. Altered plasma lipoprotein levels and tissue-specific patterns of fatty acid mobilization were the most prominent responses, emphasizing the role of lipids as the primary energy source during fasting. In plasma, very-low-density lipoprotein levels increased in food-deprived fish compared with fed fish, whereas levels of high-density lipoprotein decreased. Signs of muscle protein catabolism were also observed as changes in the alanine dynamics. The results further suggest that mechanisms to preserve liver glycogen are present in the food-deprived fish. This study thus demonstrates the utility of NMR-based metabolomics of tissue extracts and plasma to describe the integrated metabolic status of fish.
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