| 1. |
- Zillikens, M. C., et al.
(författare)
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Large meta-analysis of genome-wide association studies identifies five loci for lean body mass
- 2017
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 8:1
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Tidskriftsartikel (refereegranskat)abstract
- Lean body mass, consisting mostly of skeletal muscle, is important for healthy aging. We performed a genome-wide association study for whole body (20 cohorts of European ancestry with n = 38,292) and appendicular (arms and legs) lean body mass (n = 28,330) measured using dual energy X-ray absorptiometry or bioelectrical impedance analysis, adjusted for sex, age, height, and fat mass. Twenty-one single-nucleotide polymorphisms were significantly associated with lean body mass either genome wide (p < 5 x 10(-8)) or suggestively genome wide (p < 2.3 x 10(-6)). Replication in 63,475 (47,227 of European ancestry) individuals from 33 cohorts for whole body lean body mass and in 45,090 (42,360 of European ancestry) subjects from 25 cohorts for appendicular lean body mass was successful for five single-nucleotide polymorphisms in/ near HSD17B11, VCAN, ADAMTSL3, IRS1, and FTO for total lean body mass and for three single-nucleotide polymorphisms in/ near VCAN, ADAMTSL3, and IRS1 for appendicular lean body mass. Our findings provide new insight into the genetics of lean body mass.
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| 2. |
- Karasik, D., et al.
(författare)
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Disentangling the genetics of lean mass
- 2019
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Ingår i: American Journal of Clinical Nutrition. - : Elsevier BV. - 0002-9165 .- 1938-3207. ; 109:2, s. 276-287
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Tidskriftsartikel (refereegranskat)abstract
- Background: Lean body mass (LM) plays an important role in mobility and metabolic function. We previously identified five loci associated with LM adjusted for fat mass in kilograms. Such an adjustment may reduce the power to identify genetic signals having an association with both lean mass and fat mass. Objectives: To determine the impact of different fat mass adjustments on genetic architecture of LM and identify additional LM loci. Methods: We performed genome-wide association analyses for whole-body LM (20 cohorts of European ancestry with n = 38,292) measured using dual-energy X-ray absorptiometry) or bioelectrical impedance analysis, adjusted for sex, age, age(2), and height with or without fat mass adjustments (Model 1 no fat adjustment; Model 2 adjustment for fat mass as a percentage of body mass; Model 3 adjustment for fat mass in kilograms). Results: Seven single-nucleotide polymorphisms (SNPs) in separate loci, including one novel LM locus (TNRC6B), were successfully replicated in an additional 47,227 individuals from 29 cohorts. Based on the strengths of the associations in Model 1 vs Model 3, we divided the LM loci into those with an effect on both lean mass and fat mass in the same direction and refer to those as "sumo wrestler" loci (FTO and MC4R). In contrast, loci with an impact specifically on LMwere termed "body builder" loci (VCAN and ADAMTSL3). Using existing available genome-wide association study databases, LM increasing alleles of SNPs in sumo wrestler loci were associated with an adverse metabolic profile, whereas LM increasing alleles of SNPs in "body builder" loci were associated with metabolic protection. Conclusions: In conclusion, we identified one novel LM locus (TNRC6B). Our results suggest that a genetically determined increase in lean mass might exert either harmful or protective effects on metabolic traits, depending on its relation to fat mass.
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| 3. |
- Jiang, X., et al.
(författare)
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Genome-wide association study in 79,366 European-ancestry individuals informs the genetic architecture of 25-hydroxyvitamin D levels
- 2018
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 9:1
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Tidskriftsartikel (refereegranskat)abstract
- Vitamin D is a steroid hormone precursor that is associated with a range of human traits and diseases. Previous GWAS of serum 25-hydroxyvitamin D concentrations have identified four genome-wide significant loci (GC, NADSYN1/DHCR7, CYP2R1, CYP24A1). In this study, we expand the previous SUNLIGHT Consortium GWAS discovery sample size from 16,125 to 79,366 (all European descent). This larger GWAS yields two additional loci harboring genome-wide significant variants (P = 4.7x10(-9) at rs8018720 in SEC23A, and P = 1.9x10(-14) at rs10745742 in AMDHD1). The overall estimate of heritability of 25-hydroxyvitamin D serum concentrations attributable to GWAS common SNPs is 7.5%, with statistically significant loci explaining 38% of this total. Further investigation identifies signal enrichment in immune and hematopoietic tissues, and clustering with autoimmune diseases in cell-type-specific analysis. Larger studies are required to identify additional common SNPs, and to explore the role of rare or structural variants and gene-gene interactions in the heritability of circulating 25-hydroxyvitamin D levels.
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| 4. |
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| 5. |
- Lu, Yingchang, et al.
(författare)
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New loci for body fat percentage reveal link between adiposity and cardiometabolic disease risk
- 2016
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- To increase our understanding of the genetic basis of adiposity and its links to cardiometabolic disease risk, we conducted a genome-wide association meta-analysis of body fat percentage (BF%) in up to 100,716 individuals. Twelve loci reached genome-wide significance (P<5 × 10(-8)), of which eight were previously associated with increased overall adiposity (BMI, BF%) and four (in or near COBLL1/GRB14, IGF2BP1, PLA2G6, CRTC1) were novel associations with BF%. Seven loci showed a larger effect on BF% than on BMI, suggestive of a primary association with adiposity, while five loci showed larger effects on BMI than on BF%, suggesting association with both fat and lean mass. In particular, the loci more strongly associated with BF% showed distinct cross-phenotype association signatures with a range of cardiometabolic traits revealing new insights in the link between adiposity and disease risk.
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| 6. |
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| 7. |
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| 8. |
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| 9. |
- Scott, Robert A., et al.
(författare)
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An Expanded Genome-Wide Association Study of Type 2 Diabetes in Europeans
- 2017
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Ingår i: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 66:11, s. 2888-2902
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Tidskriftsartikel (refereegranskat)abstract
- To characterize type 2 diabetes (T2D)-associated variation across the allele frequency spectrum, we conducted a meta-analysis of genome-wide association data from 26,676 T2D case and 132,532 control subjects of European ancestry after imputation using the 1000 Genomes multiethnic reference panel. Promising association signals were followed up in additional data sets (of 14,545 or 7,397 T2D case and 38,994 or 71,604 control subjects). We identified 13 novel T2D-associated loci (P < 5 x 10(-8)), including variants near the GLP2R, GIP, and HLA-DQA1 genes. Our analysis brought the total number of independent T2D associations to 128 distinct signals at 113 loci. Despite substantially increased sample size and more complete coverage of low-frequency variation, all novel associations were driven by common single nucleotide variants. Credible sets of potentially causal variants were generally larger than those based on imputation with earlier reference panels, consistent with resolution of causal signals to common risk haplotypes. Stratification of T2D-associated loci based on T2D-related quantitative trait associations revealed tissue-specific enrichment of regulatory annotations in pancreatic islet enhancers for loci influencing insulin secretion and in adipocytes, monocytes, and hepatocytes for insulin action-associated loci. These findings highlight the predominant role played by common variants of modest effect and the diversity of biological mechanisms influencing T2D pathophysiology.
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| 10. |
- Gaulton, Kyle J, et al.
(författare)
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Genetic fine mapping and genomic annotation defines causal mechanisms at type 2 diabetes susceptibility loci.
- 2015
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 47:12, s. 1415-1415
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Tidskriftsartikel (refereegranskat)abstract
- We performed fine mapping of 39 established type 2 diabetes (T2D) loci in 27,206 cases and 57,574 controls of European ancestry. We identified 49 distinct association signals at these loci, including five mapping in or near KCNQ1. 'Credible sets' of the variants most likely to drive each distinct signal mapped predominantly to noncoding sequence, implying that association with T2D is mediated through gene regulation. Credible set variants were enriched for overlap with FOXA2 chromatin immunoprecipitation binding sites in human islet and liver cells, including at MTNR1B, where fine mapping implicated rs10830963 as driving T2D association. We confirmed that the T2D risk allele for this SNP increases FOXA2-bound enhancer activity in islet- and liver-derived cells. We observed allele-specific differences in NEUROD1 binding in islet-derived cells, consistent with evidence that the T2D risk allele increases islet MTNR1B expression. Our study demonstrates how integration of genetic and genomic information can define molecular mechanisms through which variants underlying association signals exert their effects on disease.
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| 11. |
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| 12. |
- Elks, Cathy E, et al.
(författare)
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Thirty new loci for age at menarche identified by a meta-analysis of genome-wide association studies
- 2010
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 42:12, s. 1077-85
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Tidskriftsartikel (refereegranskat)abstract
- To identify loci for age at menarche, we performed a meta-analysis of 32 genome-wide association studies in 87,802 women of European descent, with replication in up to 14,731 women. In addition to the known loci at LIN28B (P = 5.4 × 10⁻⁶⁰) and 9q31.2 (P = 2.2 × 10⁻³³), we identified 30 new menarche loci (all P < 5 × 10⁻⁸) and found suggestive evidence for a further 10 loci (P < 1.9 × 10⁻⁶). The new loci included four previously associated with body mass index (in or near FTO, SEC16B, TRA2B and TMEM18), three in or near other genes implicated in energy homeostasis (BSX, CRTC1 and MCHR2) and three in or near genes implicated in hormonal regulation (INHBA, PCSK2 and RXRG). Ingenuity and gene-set enrichment pathway analyses identified coenzyme A and fatty acid biosynthesis as biological processes related to menarche timing.
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| 13. |
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| 14. |
- Wright, G. S., et al.
(författare)
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The Mid-Infrared Instrument for the James Webb Space Telescope, II: Design and Build
- 2015
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Ingår i: Publications of the Astronomical Society of the Pacific. - : IOP Publishing. - 0004-6280 .- 1538-3873. ; 127:953, s. 595-611
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Tidskriftsartikel (refereegranskat)abstract
- The Mid-InfraRed Instrument (MIRI) on the James Webb Space Telescope (JWST) provides measurements over the wavelength range 5 to 28: 5 mu m. MIRI has, within a single "package," four key scientific functions: photometric imaging, coronagraphy, single-source low-spectral resolving power (R similar to 100) spectroscopy, and medium-resolving power (R similar to 1500 to 3500) integral field spectroscopy. An associated cooler system maintains MIRI at its operating temperature of
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| 15. |
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| 16. |
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| 17. |
- Nikpay, Majid, et al.
(författare)
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A comprehensive 1000 Genomes-based genome-wide association meta-analysis of coronary artery disease
- 2015
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 47:10, s. 1121-1121
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Tidskriftsartikel (refereegranskat)abstract
- Existing knowledge of genetic variants affecting risk of coronary artery disease (CAD) is largely based on genome-wide association study (GWAS) analysis of common SNPs. Leveraging phased haplotypes from the 1000 Genomes Project, we report a GWAS meta-analysis of similar to 185,000 CAD cases and controls, interrogating 6.7 million common (minor allele frequency (MAF) > 0.05) and 2.7 million low-frequency (0.005 < MAF < 0.05) variants. In addition to confirming most known CAD-associated loci, we identified ten new loci (eight additive and two recessive) that contain candidate causal genes newly implicating biological processes in vessel walls. We observed intralocus allelic heterogeneity but little evidence of low-frequency variants with larger effects and no evidence of synthetic association. Our analysis provides a comprehensive survey of the fine genetic architecture of CAD, showing that genetic susceptibility to this common disease is largely determined by common SNPs of small effect size.
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| 18. |
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| 19. |
- Vimaleswaran, K. S., et al.
(författare)
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Causal Relationship between Obesity and Vitamin D Status: Bi-Directional Mendelian Randomization Analysis of Multiple Cohorts
- 2013
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Ingår i: Plos Medicine. - : Public Library of Science (PLoS). - 1549-1676 .- 1549-1277. ; 10:2
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Obesity is associated with vitamin D deficiency, and both are areas of active public health concern. We explored the causality and direction of the relationship between body mass index (BMI) and 25-hydroxyvitamin D [25(OH)D] using genetic markers as instrumental variables (IVs) in bi-directional Mendelian randomization (MR) analysis. METHODS AND FINDINGS: We used information from 21 adult cohorts (up to 42,024 participants) with 12 BMI-related SNPs (combined in an allelic score) to produce an instrument for BMI and four SNPs associated with 25(OH)D (combined in two allelic scores, separately for genes encoding its synthesis or metabolism) as an instrument for vitamin D. Regression estimates for the IVs (allele scores) were generated within-study and pooled by meta-analysis to generate summary effects. Associations between vitamin D scores and BMI were confirmed in the Genetic Investigation of Anthropometric Traits (GIANT) consortium (n=123,864). Each 1 kg/m(2) higher BMI was associated with 1.15% lower 25(OH)D (p=6.52×10⁻²⁷). The BMI allele score was associated both with BMI (p=6.30×10⁻⁶²) and 25(OH)D (-0.06% [95% CI -0.10 to -0.02], p=0.004) in the cohorts that underwent meta-analysis. The two vitamin D allele scores were strongly associated with 25(OH)D (p≤8.07×10⁻⁵⁷ for both scores) but not with BMI (synthesis score, p=0.88; metabolism score, p=0.08) in the meta-analysis. A 10% higher genetically instrumented BMI was associated with 4.2% lower 25(OH)D concentrations (IV ratio: -4.2 [95% CI -7.1 to -1.3], p=0.005). No association was seen for genetically instrumented 25(OH)D with BMI, a finding that was confirmed using data from the GIANT consortium (p≥0.57 for both vitamin D scores). CONCLUSIONS: On the basis of a bi-directional genetic approach that limits confounding, our study suggests that a higher BMI leads to lower 25(OH)D, while any effects of lower 25(OH)D increasing BMI are likely to be small. Population level interventions to reduce BMI are expected to decrease the prevalence of vitamin D deficiency.
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| 20. |
- Ahlm, Lars, et al.
(författare)
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Modeling the thermodynamics and kinetics of sulfuric acid-dimethylamine-water nanoparticle growth in the CLOUD chamber
- 2016
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Ingår i: Aerosol Science and Technology. - : Informa UK Limited. - 0278-6826 .- 1521-7388. ; 50:10, s. 1017-1032
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Tidskriftsartikel (refereegranskat)abstract
- Dimethylamine (DMA) has a stabilizing effect on sulfuric acid (SA) clusters, and the SA and DMA molecules and clusters likely play important roles in both aerosol particle formation and growth in the atmosphere. We use the monodisperse particle growth model for acid-base chemistry in nanoparticle growth (MABNAG) together with direct and indirect observations from the CLOUD4 and CLOUD7 experiments in the cosmics leaving outdoor droplets (CLOUD) chamber at CERN to investigate the size and composition evolution of freshly formed particles consisting of SA, DMA, and water as they grow to 20nm in dry diameter. Hygroscopic growth factors are measured using a nano-hygroscopicity tandem differential mobility analyzer (nano-HTDMA), which combined with simulations of particle water uptake using the thermodynamic extended-aerosol inorganics model (E-AIM) constrain the chemical composition. MABNAG predicts a particle-phase ratio between DMA and SA molecules of 1.1-1.3 for a 2nm particle and DMA gas-phase mixing ratios between 3.5 and 80 pptv. These ratios agree well with observations by an atmospheric-pressure interface time-of-flight (APi-TOF) mass spectrometer. Simulations with MABNAG, direct observations of the composition of clusters <2nm, and indirect observations of the particle composition indicate that the acidity of the nucleated particles decreases as they grow from approximate to 1 to 20nm. However, MABNAG predicts less acidic particles than suggested by the indirect estimates at 10nm diameter using the nano-HTDMA measurements, and less acidic particles than observed by a thermal desorption chemical ionization mass spectrometer (TDCIMS) at 10-30nm. Possible explanations for these discrepancies are discussed.
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| 21. |
- Álvarez-Márquez, J., et al.
(författare)
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MIRI/JWST observations reveal an extremely obscured starburst in the z = 6.9 system SPT0311-58
- 2023
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 671
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Tidskriftsartikel (refereegranskat)abstract
- Luminous infrared starbursts in the early Universe are thought to be the progenitors of massive quiescent galaxies identified at redshifts 2–4. Using the Mid-IRfrared Instrument (MIRI) on board the James Webb Space Telescope (JWST), we present mid-infrared sub-arcsec imaging and spectroscopy of such a starburst: the slightly lensed hyper-luminous infrared system SPT0311-58 at z = 6.9. The MIRI IMager (MIRIM) and Medium Resolution Spectrometer (MRS) observations target the stellar (rest-frame 1.26 μm emission) structure and ionised (Paα and Hα) medium on kpc scales in the system. The MIRI observations are compared with existing ALMA far-infrared continuum and [C II]158μm imaging at a similar angular resolution. Even though the ALMA observations imply very high star formation rates (SFRs) in the eastern (E) and western (W) galaxies of the system, the Hα line is, strikingly, not detected in our MRS observations. This fact, together with the detection of the ionised gas phase in Paα, implies very high internal nebular extinction with lower limits (AV) of 4.2 (E) and 3.9 mag (W) as well as even larger values (5.6 (E) and 10.0 (W)) by spectral energy distribution (SED) fitting analysis. The extinction-corrected Paα lower limits of the SFRs are 383 and 230 M⊙ yr−1 for the E and W galaxies, respectively. This represents 50% of the SFRs derived from the [C II]158 μm line and infrared light for the E galaxy and as low as 6% for the W galaxy. The MIRIM observations reveal a clumpy stellar structure, with each clump having 3–5×109 M⊙ mass in stars, leading to a total stellar mass of 2.0 and 1.5×1010 M⊙ for the E and W galaxies, respectively. The specific star formation (sSFR) in the stellar clumps ranges from 25 to 59 Gyr−1, assuming a star formation with a 50–100 Myr constant rate. This sSFR is three to ten times larger than the values measured in galaxies of similar stellar mass at redshifts 6–8. Thus, SPT0311-58 clearly stands out as a starburst system when compared with typical massive star-forming galaxies at similar high redshifts. The overall gas mass fraction is Mgas/M∗ ∼ 3, similar to that of z ∼ 4.5–6 star-forming galaxies, suggesting a flattening of the gas mass fraction in massive starbursts up to redshift 7. The kinematics of the ionised gas in the E galaxy agrees with the known [C II] gas kinematics, indicating a physical association between the ionised gas and the cold ionised or neutral gas clumps. The situation in the W galaxy is more complex, as it appears to be a velocity offset by about +700 km s−1 in the Paα relative to the [C II] emitting gas. The nature of this offset and its reality are not fully established and require further investigation. The observed properties of SPT0311-58, such as the clumpy distribution at sub(kpc) scales and the very high average extinction, are similar to those observed in low- and intermediate-z luminous (E galaxy) and ultra-luminous (W galaxy) infrared galaxies, even though SPT0311-58 is observed only ∼800 Myr after the Big Bang. Such massive, heavily obscured clumpy starburst systems as SPT0311-58 likely represent the early phases in the formation of a massive high-redshift bulge, spheroids and/or luminous quasars. This study demonstrates that MIRI and JWST are, for the first time, able to explore the rest-frame near-infrared stellar and ionised gas structure of these galaxies, even during the Epoch of Reionization.
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| 22. |
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| 23. |
- Kilpeläinen, Tuomas O, et al.
(författare)
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Genetic variation near IRS1 associates with reduced adiposity and an impaired metabolic profile.
- 2011
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Ingår i: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 43:8, s. 753-60
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies have identified 32 loci influencing body mass index, but this measure does not distinguish lean from fat mass. To identify adiposity loci, we meta-analyzed associations between ∼2.5 million SNPs and body fat percentage from 36,626 individuals and followed up the 14 most significant (P < 10(-6)) independent loci in 39,576 individuals. We confirmed a previously established adiposity locus in FTO (P = 3 × 10(-26)) and identified two new loci associated with body fat percentage, one near IRS1 (P = 4 × 10(-11)) and one near SPRY2 (P = 3 × 10(-8)). Both loci contain genes with potential links to adipocyte physiology. Notably, the body-fat-decreasing allele near IRS1 is associated with decreased IRS1 expression and with an impaired metabolic profile, including an increased visceral to subcutaneous fat ratio, insulin resistance, dyslipidemia, risk of diabetes and coronary artery disease and decreased adiponectin levels. Our findings provide new insights into adiposity and insulin resistance.
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| 24. |
- Rinaldi, P., et al.
(författare)
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MIDIS : Strong (H beta plus [OIII]) and Ha Emitters at Redshift z similar or equal to 7-8 Unveiled with JWST NIRCam and MIRI Imaging in the Hubble eXtreme Deep Field
- 2023
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Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 952:2
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Tidskriftsartikel (refereegranskat)abstract
- We make use of JWST medium-band and broadband NIRCam imaging, along with ultradeep MIRI 5.6 mu m imaging, in the Hubble eXtreme Deep Field to identify prominent line emitters at z similar or equal to 7-8. Out of a total of 58 galaxies at z similar or equal to 7-8, we find 18 robust candidates ( similar or equal to 31%) for (H beta + [O III]) emitters, based on their enhanced fluxes in the F430M and F444W filters, with EW0(H beta +[O III]) similar or equal to 87-2100 angstrom. Among these emitters, 16 lie in the MIRI coverage area and 12 exhibit a clear flux excess at 5.6 mu m, indicating the simultaneous presence of a prominent Ha emission line with EW0(H alpha) similar or equal to 200-3000 angstrom. This is the first time that H alpha emission can be detected in individual galaxies at z > 7. The Ha line, when present, allows us to separate the contributions of H beta and [O III] to the (H beta +[O III]) complex and derive Ha-based star formation rates (SFRs). We find that in most cases [O III]/ H beta > 1. Instead, two galaxies have [O III]/H beta < 1, indicating that the NIRCam flux excess is mainly driven by H beta. Most prominent line emitters are very young starbursts or galaxies on their way to/from the starburst cloud. They make for a cosmic SFR density log(10)( rho(SFRH alpha) (M-circle dot yr(-1) Mpc))similar or equal to - 2.351 3 which is about a quarter of the total value (log(10)( SFR (M-circle dot yr(-1) Mpc))similar or equal to - 1.761 3 ) at z similar or equal to 7-8. Therefore, the strong Ha emitters likely had a significant role in reionization.
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| 25. |
- Wright, Gillian, et al.
(författare)
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The Mid-infrared Instrument for JWST and Its In-flight Performance
- 2023
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Ingår i: Publications of the Astronomical Society of the Pacific. - 0004-6280 .- 1538-3873. ; 135:1046
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Tidskriftsartikel (refereegranskat)abstract
- The Mid-Infrared Instrument (MIRI) extends the reach of the James Webb Space Telescope (JWST) to 28.5 μm. It provides subarcsecond-resolution imaging, high sensitivity coronagraphy, and spectroscopy at resolutions of λ/Δλ ∼ 100-3500, with the high-resolution mode employing an integral field unit to provide spatial data cubes. The resulting broad suite of capabilities will enable huge advances in studies over this wavelength range. This overview describes the history of acquiring this capability for JWST. It discusses the basic attributes of the instrument optics, the detector arrays, and the cryocooler that keeps everything at approximately 7 K. It gives a short description of the data pipeline and of the instrument performance demonstrated during JWST commissioning. The bottom line is that the telescope and MIRI are both operating to the standards set by pre-launch predictions, and all of the MIRI capabilities are operating at, or even a bit better than, the level that had been expected. The paper is also designed to act as a roadmap to more detailed papers on different aspects of MIRI.
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| 26. |
- Bouchet, P., et al.
(författare)
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JWST MIRI Imager Observations of Supernova SN 1987A
- 2024
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Ingår i: Astrophysical Journal. - : American Astronomical Society. - 0004-637X .- 1538-4357. ; 965:1
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Tidskriftsartikel (refereegranskat)abstract
- There exist very few mid-infrared (IR) observations of supernovae (SNe) in general. Therefore, SN 1987A, the closest visible SN in 400 yr, gives us the opportunity to explore the mid-IR properties of SNe, the dust in their ejecta, and the surrounding medium and to witness the birth of an SN remnant (SNR). The James Webb Space Telescope, with its high spatial resolution and extreme sensitivity, gives a new view on these issues. We report on the first imaging observations obtained with the Mid-InfraRed Instrument (MIRI). We build temperature maps and discuss the morphology of the nascent SNR. Our results show that the temperatures in the equatorial ring (ER) are quite nonuniform. This could be due to dust destruction in some parts of the ring, as had been assumed in some previous works. We show that the IR emission extends beyond the ER, illustrating the fact that the shock wave has now passed through this ring to affect the circumstellar medium on a larger scale. Finally, while submillimeter Atacama Large Millimeter Array observations have hinted at the location of the compact remnant of SN 1987A, we note that our MIRI data have found no such evidence.
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| 27. |
- Fransson, Claes, 1951-, et al.
(författare)
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Emission lines due to ionizing radiation from a compact object in the remnant of Supernova 1987A
- 2024
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 383:6685, s. 898-903
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Tidskriftsartikel (refereegranskat)abstract
- The nearby Supernova 1987A was accompanied by a burst of neutrino emission, which indicates that a compact object (a neutron star or black hole) was formed in the explosion. There has been no direct observation of this compact object. In this work, we observe the supernova remnant with JWST spectroscopy, finding narrow infrared emission lines of argon and sulfur. The line emission is spatially unresolved and blueshifted in velocity relative to the supernova rest frame. We interpret the lines as gas illuminated by a source of ionizing photons located close to the center of the expanding ejecta. Photoionization models show that the line ratios are consistent with ionization by a cooling neutron star or a pulsar wind nebula. The velocity shift could be evidence for a neutron star natal kick.
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| 28. |
- Jones, O. C., et al.
(författare)
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Ejecta, Rings, and Dust in SN 1987A with JWST MIRI/MRS
- 2023
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Ingår i: Astrophysical Journal. - : American Astronomical Society. - 0004-637X .- 1538-4357. ; 958:1
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Tidskriftsartikel (refereegranskat)abstract
- Supernova (SN) 1987A is the nearest supernova in ∼400 yr. Using the JWST MIRI Medium Resolution Spectrograph, we spatially resolved the ejecta, equatorial ring (ER), and outer rings in the mid-infrared 12,927 days (35.4 yr) after the explosion. The spectra are rich in line and dust continuum emission, both in the ejecta and the ring. The broad emission lines (280–380 km s−1 FWHM) that are seen from all singly-ionized species originate from the expanding ER, with properties consistent with dense post-shock cooling gas. Narrower emission lines (100–170 km s−1 FWHM) are seen from species originating from a more extended lower-density component whose high ionization may have been produced by shocks progressing through the ER or by the UV radiation pulse associated with the original supernova event. The asymmetric east–west dust emission in the ER has continued to fade, with constant temperature, signifying a reduction in dust mass. Small grains in the ER are preferentially destroyed, with larger grains from the progenitor surviving the transition from SN into SNR. The ER dust is fit with a single set of optical constants, eliminating the need for a secondary featureless hot dust component. We find several broad ejecta emission lines from [Ne ii], [Ar ii], [Fe ii], and [Ni ii]. With the exception of [Fe ii] 25.99 μm, these all originate from the ejecta close to the ring and are likely to be excited by X-rays from the interaction. The [Fe ii] 5.34 to 25.99 μm line ratio indicates a temperature of only a few hundred K in the inner core, which is consistent with being powered by 44 Ti decay.
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| 29. |
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| 30. |
- Sandholm, Niina, et al.
(författare)
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New susceptibility loci associated with kidney disease in type 1 diabetes
- 2012
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Ingår i: PLOS Genetics. - San Francisco, USA : Public Library of Science, PLOS. - 1553-7390 .- 1553-7404. ; 8:9, s. e1002921-
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Tidskriftsartikel (refereegranskat)abstract
- Diabetic kidney disease, or diabetic nephropathy (DN), is a major complication of diabetes and the leading cause of end-stage renal disease (ESRD) that requires dialysis treatment or kidney transplantation. In addition to the decrease in the quality of life, DN accounts for a large proportion of the excess mortality associated with type 1 diabetes (T1D). Whereas the degree of glycemia plays a pivotal role in DN, a subset of individuals with poorly controlled T1D do not develop DN. Furthermore, strong familial aggregation supports genetic susceptibility to DN. However, the genes and the molecular mechanisms behind the disease remain poorly understood, and current therapeutic strategies rarely result in reversal of DN. In the GEnetics of Nephropathy: an International Effort (GENIE) consortium, we have undertaken a meta-analysis of genomewide association studies (GWAS) of T1D DN comprising similar to 2.4 million single nucleotide polymorphisms (SNPs) imputed in 6,691 individuals. After additional genotyping of 41 top ranked SNPs representing 24 independent signals in 5,873 individuals, combined meta-analysis revealed association of two SNPs with ESRD: rs7583877 in the AFF3 gene (P = 1.2 x 10(-8)) and an intergenic SNP on chromosome 15q26 between the genes RGMA and MCTP2, rs12437854 (P = 2.0 x 10(-9)). Functional data suggest that AFF3 influences renal tubule fibrosis via the transforming growth factor-beta (TGF-beta 1) pathway. The strongest association with DN as a primary phenotype was seen for an intronic SNP in the ERBB4 gene (rs7588550, P = 2.1 x 10(-7)), a gene with type 2 diabetes DN differential expression and in the same intron as a variant with cis-eQTL expression of ERBB4. All these detected associations represent new signals in the pathogenesis of DN.
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| 31. |
- Tikkanen, R., et al.
(författare)
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Influence of a HTR2B Stop Codon on Glucagon Homeostasis and Glucose Excursion in Non-Diabetic Men
- 2016
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Ingår i: Experimental and clinical endocrinology & diabetes. - : Georg Thieme Verlag KG. - 0947-7349 .- 1439-3646. ; 124:9, s. 529-534
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Tidskriftsartikel (refereegranskat)abstract
- Limited data are available about the role of the serotonin 2B (5-HT2B) receptor in the function of human islets. This study aimed to test whether the 5-HT2B receptor contributes to glucose, insulin, and glucagon homeostasis in humans, utilizing a hereditary loss-of-function gene mutation in the receptor, which causes a 50% reduction in the production of the receptor protein in heterozygotes. This clinical study enrolled participants recruited by newspaper advertisements and from mental status examinations. A cohort of participants from a young Finnish founder population composed of 68 non-diabetic males with a mean age of 30 was divided into groups for comparison based on being a 5-HT2B receptor loss-of-function gene mutation (HTR2B Q20*) heterozygote carrier (n=11) or not (n=57). Serum levels of glucose, insulin, and glucagon were measured in a 5h oral glucose tolerance test using a 75g glucose challenge. Insulin resistance, insulin sensitivity, and beta cell activity were calculated using the homeostasis model assessment (HOMA2) and whole body insulin sensitivity index (WBISI), as well as the ratio of glucagon to insulin was noted. The areas under the curves (AUCs) were also determined. Concentrations of the serotonin metabolite 5-hydroxyindoleacetic acid (5-HIAA) were measured in cerebrospinal fluid (CSF). Covariate adjusted mean score comparisons were applied. Lower glucagon secretion and decreased glucose excursion were observed among HTR2B Q20* carriers as compared with individuals who were homozygotes for the wild-type Q20 allele (controls). No differences in insulin secretion, beta cell activity, insulin resistance, or insulin sensitivity were observed. The glucagon to insulin ratio differed between the HTR2B Q20* carriers and controls. CSF levels of 5-HIAA were similar between groups. Our findings indicate that the 5-HT2B receptor may contribute to the regulation of human glucagon and glucose homeostasis and the interplay between glucagon and insulin secretion.
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| 32. |
- Vimaleswaran, Karani S, et al.
(författare)
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Association of vitamin D status with arterial blood pressure and hypertension risk: a mendelian randomisation study.
- 2014
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Ingår i: The lancet. Diabetes & endocrinology. - 2213-8595 .- 2213-8587. ; 2:9, s. 719-29
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Tidskriftsartikel (refereegranskat)abstract
- Background Low plasma 25-hydroxyvitamin D (25[OH]D) concentration is associated with high arterial blood pressure and hypertension risk, but whether this association is causal is unknown. We used a mendelian randomisation approach to test whether 25(OH)D concentration is causally associated with blood pressure and hypertension risk. Methods In this mendelian randomisation study, we generated an allele score (25[OH]D synthesis score) based on variants of genes that affect 25(OH)D synthesis or substrate availability (CYP2R1 and DHCR7), which we used as a proxy for 25(OH)D concentration. We meta-analysed data for up to 108173 individuals from 35 studies in the D-CarDia collaboration to investigate associations between the allele score and blood pressure measurements. We complemented these analyses with previously published summary statistics from the International Consortium on Blood Pressure (ICBP), the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium, and the Global Blood Pressure Genetics (Global BPGen) consortium. Findings In phenotypic analyses (up to n=49363), increased 25(OH)D concentration was associated with decreased systolic blood pressure (β per 10% increase, −0·12 mm Hg, 95% CI −0·20 to −0·04; p=0·003) and reduced odds of hypertension (odds ratio [OR] 0·98, 95% CI 0·97–0·99; p=0·0003), but not with decreased diastolic blood pressure (β per 10% increase, −0·02 mm Hg, −0·08 to 0·03; p=0·37). In meta-analyses in which we combined data from D-CarDia and the ICBP (n=146581, after exclusion of overlapping studies), each 25(OH)D-increasing allele of the synthesis score was associated with a change of −0·10 mm Hg in systolic blood pressure (−0·21 to −0·0001; p=0·0498) and a change of −0·08 mm Hg in diastolic blood pressure (−0·15 to −0·02; p=0·01). When D-CarDia and consortia data for hypertension were meta-analysed together (n=142255), the synthesis score was associated with a reduced odds of hypertension (OR per allele, 0·98, 0·96–0·99; p=0·001). In instrumental variable analysis, each 10% increase in genetically instrumented 25(OH)D concentration was associated with a change of −0·29 mm Hg in diastolic blood pressure (−0·52 to −0·07; p=0·01), a change of −0·37 mm Hg in systolic blood pressure (−0·73 to 0·003; p=0·052), and an 8·1% decreased odds of hypertension (OR 0·92, 0·87–0·97; p=0·002). Interpretation Increased plasma concentrations of 25(OH)D might reduce the risk of hypertension. This finding warrants further investigation in an independent, similarly powered study.
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| 33. |
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| 34. |
- Colina, L., et al.
(författare)
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Uncovering the stellar structure of the dusty star-forming galaxy GN20 at z=4.055 with MIRI/JWST
- 2023
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Ingår i: Astronomy and Astrophysics. - 0004-6361 .- 1432-0746. ; 673
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Tidskriftsartikel (refereegranskat)abstract
- Luminous infrared galaxies at high redshifts (z > 4) include extreme starbursts that build their stellar mass over short periods of time, that is, of 100 Myr or less. These galaxies are considered to be the progenitors of massive quiescent galaxies at intermediate redshifts (z similar to 2) but their stellar structure and buildup is unknown. Here, we present the first spatially resolved near-infrared (rest-frame 1.1 mu m) imaging of GN20, one of the most luminous dusty star-forming galaxies known to date, observed at an epoch when the Universe was only 1.5 Gyr old. The 5.6 mu m image taken with the JWST Mid-Infrared Instrument (MIRI/JWST) shows that GN20 is a very luminous galaxy (M-1.1 mu m,M- AB = 25.01, uncorrected for internal extinction), with a stellar structure composed of a conspicuous central source and an extended envelope. The central source is an unresolved nucleus that carries 9% of the total flux. The nucleus is co-aligned with the peak of the cold dust emission, and offset by 3.9 kpc from the ultraviolet stellar emission. The diffuse stellar envelope is similar in size (3.6 kpc effective radius) to the clumpy CO molecular gas distribution. The centroid of the stellar envelope is offset by 1 kpc from the unresolved nucleus, suggesting GN20 is involved in an interaction or merger event supported by its location as the brightest galaxy in a proto-cluster. Additional faint stellar clumps appear to be associated with some of the UV- and CO-clumps. The stellar size of GN20 is larger by a factor of about 3 to 5 than known spheroids, disks, and irregulars at z similar to 4, while its size and low Sersic index are similar to those measured in dusty, infrared luminous galaxies at redshift 2 of the same mass (similar to 10(11) M-circle dot). GN20 has all the ingredients necessary for evolving into a massive spheroidal quiescent galaxy at intermediate redshift: it is a large, luminous galaxy at z = 4.05 involved in a short and massive starburst centred in the stellar nucleus and extended over the entire galaxy, out to radii of 4 kpc, and likely induced by the interaction or merger with a member of the proto-cluster.
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| 35. |
- Larsson, Josefin, et al.
(författare)
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JWST NIRSpec Observations of Supernova 1987A : From the Inner Ejecta to the Reverse Shock
- 2023
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Ingår i: Astrophysical Journal Letters. - : American Astronomical Society. - 2041-8205 .- 2041-8213. ; 949:2
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Tidskriftsartikel (refereegranskat)abstract
- We present initial results from JWST NIRSpec integral field unit observations of the nearby supernova SN 1987A. The observations provide the first spatially resolved spectroscopy of the ejecta and equatorial ring (ER) over the 1-5 μm range. We construct 3D emissivity maps of the [Fe i] 1.443 μm line from the inner ejecta and the He i 1.083 μm line from the reverse shock (RS), where the former probes the explosion geometry and the latter traces the structure of the circumstellar medium. We also present a model for the integrated spectrum of the ejecta. The [Fe i] 3D map reveals a highly asymmetric morphology resembling a broken dipole, dominated by two large clumps with velocities of ∼2300 km s−1. We also find evidence that the Fe-rich inner ejecta have started to interact with the RS. The RS surface traced by the He i line extends from just inside the ER to higher latitudes on both sides of the ER with a half-opening angle ∼45°, forming a bubble-like structure. The spectral model for the ejecta allows us to identify the many emission lines, including numerous H2 lines. We find that the H2 is most likely excited by far-UV emission, while the metal-line ratios are consistent with a combination of collisional excitation and recombination in the low-temperature ejecta. We also find several high-ionization coronal lines from the ER, requiring a temperature ≳2 × 106 K.
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| 36. |
- Surakka, Ida, et al.
(författare)
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A Genome-Wide Screen for Interactions Reveals a New Locus on 4p15 Modifying the Effect of Waist-to-Hip Ratio on Total Cholesterol
- 2011
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Ingår i: PLoS Genetics. - : Public Library of Science (PLoS). - 1553-7390 .- 1553-7404. ; 7:10, s. e1002333-
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Tidskriftsartikel (refereegranskat)abstract
- Recent genome-wide association (GWA) studies described 95 loci controlling serum lipid levels. These common variants explain similar to 25% of the heritability of the phenotypes. To date, no unbiased screen for gene-environment interactions for circulating lipids has been reported. We screened for variants that modify the relationship between known epidemiological risk factors and circulating lipid levels in a meta-analysis of genome-wide association (GWA) data from 18 population-based cohorts with European ancestry (maximum N = 32,225). We collected 8 further cohorts (N = 17,102) for replication, and rs6448771 on 4p15 demonstrated genome-wide significant interaction with waist-to-hip-ratio (WHR) on total cholesterol (TC) with a combined P-value of 4.79 x 10(-9). There were two potential candidate genes in the region, PCDH7 and CCKAR, with differential expression levels for rs6448771 genotypes in adipose tissue. The effect of WHR on TC was strongest for individuals carrying two copies of G allele, for whom a one standard deviation (sd) difference in WHR corresponds to 0.19 sd difference in TC concentration, while for A allele homozygous the difference was 0.12 sd. Our findings may open up possibilities for targeted intervention strategies for people characterized by specific genomic profiles. However, more refined measures of both body-fat distribution and metabolic measures are needed to understand how their joint dynamics are modified by the newly found locus.
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| 37. |
- Tikkanen, M.J., et al.
(författare)
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Comparison of Efficacy and Safety of Atorvastatin (80 mg) to Simvastatin (20 to 40 mg) in Patients Aged less than65 Versus =65 Years With Coronary Heart Disease (from the Incremental DEcrease through Aggressive Lipid Lowering [IDEAL] Study)
- 2009
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Ingår i: American Journal of Cardiology. - : Elsevier BV. - 0002-9149. ; 103:5, s. 577-582
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Tidskriftsartikel (refereegranskat)abstract
- The efficacy and safety of atorvastatin (80 mg/day) versus simvastatin (20 to 40 mg/day) in older (age =65 years) versus younger (less than65 years) patients were assessed in a prespecified secondary analysis of the 8,888 patients with myocardial infarction in the IDEAL trial, a randomized open-label study. Several cardiovascular end points were evaluated, including the occurrence of a first major coronary event (MCE; nonfatal myocardial infarction, coronary heart disease death, or resuscitated cardiac arrest), the primary end point of the trial, and occurrence of any cardiovascular event (MCE, stroke, revascularization, unstable angina, congestive heart failure, and peripheral artery disease). Although there were no significant interactions between age and treatment, the magnitude of effect in favor of atorvastatin was higher in younger versus older patients (occurrence of first MCE, hazard ratio [HR] 0.80, 95% confidence interval [CI] 0.66 to 0.98; and HR 0.95, 95% CI 0.80 to 1.15, respectively; occurrence of any cardiovascular (CV) event, HR 0.80, 95% CI 0.71 to 0.89; and HR 0.88, 95% CI 0.79 to 0.99, respectively). These results were likely influenced by adherence, which was lower in older patients and those receiving atorvastatin compared with those receiving simvastatin. Rates of any reported serious adverse event were higher in older patients, but did not differ between the 2 statin groups. In conclusion, except for any CV events in the older group, significant reductions in primary and secondary end points were observed only in patients less than65 years of age. The safety of atorvastatin (80 mg) and simvastatin (20 to 40 mg) was similar in patients aged less than65 and greater than65 years with stable coronary disease.
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| 38. |
- van, der Steeg W.A., et al.
(författare)
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High-Density Lipoprotein Cholesterol, High-Density Lipoprotein Particle Size, and Apolipoprotein A-I : Significance for Cardiovascular Risk. The IDEAL and EPIC-Norfolk Studies
- 2008
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Ingår i: Journal of the American College of Cardiology. - : Elsevier BV. - 0735-1097 .- 1558-3597. ; 51:6, s. 634-642
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: This study was designed to assess the relationship of high-density-lipoprotein cholesterol (HDL-C), HDL particle size, and apolipoprotein A-I (apoA-I) with the occurrence of coronary artery disease (CAD), with a focus on the effect of very high values of these parameters. Background: High plasma levels of HDL-C and apoA-I are inversely related to the risk of CAD. However, recent data suggest that this relationship does not hold true for very high HDL-C levels, particularly when a preponderance of large HDL particles is observed. Methods: We conducted a post-hoc analysis of 2 prospective studies: the IDEAL (Incremental Decrease in End Points through Aggressive Lipid Lowering, n = 8,888) trial comparing the efficacy of high-dose to usual-dose statin treatment for the secondary prevention of cardiovascular events, and the EPIC (European Prospective Investigation into Cancer and Nutrition)-Norfolk case-control study, including apparently healthy individuals who did (cases, n = 858) or did not (control patients, n = 1,491) develop CAD during follow-up. In IDEAL, only HDL-C and apoA-I were available, in EPIC-Norfolk, nuclear magnetic resonance spectroscopy-determined HDL particle sizes were also available. Results: In the IDEAL study, higher HDL-C proved a significant major cardiac event risk factor following adjustment for age, gender, smoking, apoA-I, and apoB. A similar association was observed for HDL particle size in EPIC-Norfolk. Increased risk estimates were particularly present in the high ends of the distributions. In contrast, apoA-I remained negatively associated across the major part of its distribution in both studies. Conclusions: When apoA-I and apoB are kept constant, HDL-C and HDL particle size may confer risk at very high values. This does not hold true for very high levels of apoA-I at fixed levels of HDL-C and apoB. These findings may have important consequences for assessment and treatment of CAD risk. © 2008 American College of Cardiology Foundation.
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| 39. |
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| 40. |
- Gordin, D., et al.
(författare)
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The effects of baroreflex activation therapy on blood pressure and sympathetic function in patients with refractory hypertension: the rationale and design of the Nordic BAT study
- 2017
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Ingår i: Blood Pressure. - : Informa UK Limited. - 0803-7051 .- 1651-1999. ; 26:5, s. 294-302
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To explore the effects of baroreflex activation therapy (BAT) on hypertension in patients with treatment resistant or refractory hypertension.Methods: This investigator-initiated randomized, double-blind, 1:1 parallel-design clinical trial will include 100 patients with refractory hypertension from 6 tertiary referral hypertension centers in the Nordic countries. A Barostim Neo System will be implanted and after 1 month patients will be randomized to either BAT for 16 months or continuous pharmacotherapy (BAT off) for 8 months followed by BAT for 8 months. A second randomization will take place after 16 months to BAT or BAT off for 3 months. Eligible patients have a daytime systolic ambulatory blood pressure (ABPM) of 145mm Hg, and/or a daytime diastolic ABPM of 95mm Hg after witnessed drug intake (including 3 antihypertensive drugs, preferably including a diuretic).Results: The primary end point is the reduction in 24-hour systolic ABPM by BAT at 8 months, as compared to pharmacotherapy. Secondary and tertiary endpoints are effects of BAT on home and office blood pressures, measures of indices of cardiac and vascular structure and function during follow-up, and safety.Conclusions: This academic initiative will increase the understanding of mechanisms and role of BAT in the refractory hypertension.
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| 41. |
- Holme, I, et al.
(författare)
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Cardiovascular outcomes and their relationships to lipoprotein components in patients with and without chronic kidney disease: results from the IDEAL trial
- 2010
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Ingår i: JOURNAL OF INTERNAL MEDICINE. - : Blackwell Publishing Ltd. - 0954-6820. ; 267:6, s. 567-575
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Tidskriftsartikel (refereegranskat)abstract
- Cardiovascular outcomes and their relationships to lipoprotein components in patients with and without chronic kidney disease: Results from the IDEAL trial. J Intern Med 2010; 267:567-575. Objectives. In Incremental Decrease in Endpoints through Aggressive Lipid-lowering (IDEAL), we compared cardiovascular outcomes in patients with and without chronic kidney disease (CKD) (estimated glomerular filtration rate andlt; 60 mL min-1 1.73 m-2) and analysed relationships between lipoprotein components (LC) and major coronary events (MCE) and other cardiovascular (CV) events. Design. Exploratory analysis of CV endpoints in a randomized trial comparing high dose of atorvastatin to usual dose of simvastatin on MCE. Settings. Patients with CKD were compared with the non-CKD patients. Cox regression models were used to study the relationships between on-treatment levels of LC and incident MCE. Findings. Chronic kidney disease was strongly associated with cardiovascular end-points including total mortality. In patients with CKD, a significant benefit of high dose atorvastatin treatment was found for any CV events, stroke and peripheral artery disease, but not for MCE. However, all cardiovascular end-points except stroke and CV mortality were reduced in the non-CKD group. Differential changes in LC or relationships to LC could not explain the different treatment outcomes in MCE in the two groups. Interpretation. Chronic kidney disease was a powerful risk factor for all cardiovascular end-points. The reason why the significant reductions achieved by high-dose statin treatment in most CV end-points in the non-CKD group were only in part matched by similar reductions in the CKD patients is not apparent. This difference did not result from differential changes in or relations to LC, but limited power may have increased the possibility of chance findings.
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| 42. |
- Holme, I., et al.
(författare)
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Lipoprotein predictors of cardiovascular events in statin-treated patients with coronary heart disease. Insights from the Incremental Decrease in End-points through Aggressive Lipid-lowering Trial (IDEAL)
- 2008
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Ingår i: Annals of Medicine. - : Informa UK Limited. - 0785-3890 .- 1365-2060. ; 40:6, s. 456-464
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Tidskriftsartikel (refereegranskat)abstract
- Background. Few studies have looked into the ability of measurements of apolipoprotein B (apoB) and apolipoprotein A-1 (apoA-1) or apoB/apoA-1 to predict new coronary heart disease (CHD) events in patients with CHD on statin treatment. Aims. In the IDEAL trial, to compare lipoprotein components to predict CHD events and to what degree differences in those parameters could explain the observed outcome. Methods. We compared the ability of treatment with atorvastatin 80 mg/day to that of simvastatin 20-40 mg/day to prevent CHD events in patients with CHD and used Cox regression models to study the relationships between on-treatment levels of lipoprotein components to subsequent major coronary events (MCE). Findings. Variables related to low-density lipoprotein cholesterol (LDL-C) carried more predictive information than those related to high-density lipoprotein cholesterol (HDL-C), but LDL-C was less predictive than both non-HDL-C and apoB. The ratio of apoB to apoA-1 was most strongly related to MCE. However, for estimating differences in relative risk reduction between the treatment groups, apoB and non-HDL-C were the strongest predictors. Interpretation. The on-treatment level of apoB/apoA-1 was the strongest predictor of MCE in the pooled patient population, whereas apoB and non-HDL-C were best able to explain the difference in outcome between treatment groups. Measurements of apoB and apoA-1 should be more widely available for routine clinical assessments. © 2008 Informa UK Ltd. (Informa Healthcare, Taylor & Francis AS).
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| 43. |
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| 44. |
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| 45. |
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| 46. |
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| 47. |
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| 48. |
- Pedersen, T.R., et al.
(författare)
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Design and baseline characteristics of the Incremental Decrease in End Points through Aggressive Lipid Lowering study
- 2004
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Ingår i: American Journal of Cardiology. - : Elsevier BV. - 0002-9149 .- 1879-1913. ; 94:6, s. 720-724
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Tidskriftsartikel (refereegranskat)abstract
- The Incremental Decrease in End Points through Aggressive Lipid Lowering (IDEAL) study is an investigator-initiated trial designed to determine whether additional clinical benefit might be gained through a strategy that decreases levels of low-density lipoprotein cholesterol levels better than those currently achieved with established statin therapy in patients who have coronary heart disease. IDEAL is a multicenter prospective, randomized, open-label, blinded, end point classification study. Patients who had myocardial infarction were randomized to prescription treatment with 80 mg/day of atorvastatin or 20 mg/day of simvastatin (the dose was increased to 40 mg/day at week 24 in those patients whose plasma total cholesterol remained >5.0 mmol/L, or 190 mg/dl, or whose low-density lipoprotein cholesterol remained >3.0 mmol/L, or 115 mg/dl). The primary clinical outcome variable is the time to initial occurrence of a major coronary event, which is defined as nonfatal acute myocardial infarction, coronary death, or resuscitated cardiac arrest. The study is designed to have a power of 90% to detect a relative decrease of 20% in the atorvastatin-group compared with the simvastatin-group in the number of major events caused by coronary heart disease over ~5.5 years. The 8,888 randomized patients had the following characteristics: mean age 61.7 ± 9.5 years, 19.1% women (mean age 64.0 ± 9.5 years), baseline total cholesterol 5.1 ± 1.0 mmol/L (197 mg/dl), low-density lipoprotein cholesterol 3.2 ± 0.9 mmol/L (124 mg/dl), and high-density lipoprotein cholesterol 1.2 ± 0.3 mmol/L (46 mg/dl). Drug treatment before randomization consisted of statins in 77% of patients, aspirin in 78.9%, ß blockers in 75.1%, and angiotensin-converting enzyme inhibitors in 30%. © 2004 by Excerpta Medica, Inc.
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| 49. |
- Pedersen, T.R., et al.
(författare)
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High-dose statins and the IDEAL study : Reply
- 2006
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Ingår i: Journal of the American Medical Association (JAMA). - : American Medical Association. - 0098-7484 .- 1538-3598. ; 295:21, s. 2478-2479
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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