| 1. |
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| 2. |
- Zillikens, M. C., et al.
(author)
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Large meta-analysis of genome-wide association studies identifies five loci for lean body mass
- 2017
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In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 8:1
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Journal article (peer-reviewed)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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| 3. |
- Jiang, X., et al.
(author)
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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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In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 9:1
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Journal article (peer-reviewed)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. |
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| 6. |
- Karasik, D., et al.
(author)
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Disentangling the genetics of lean mass
- 2019
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In: American Journal of Clinical Nutrition. - : Elsevier BV. - 0002-9165 .- 1938-3207. ; 109:2, s. 276-287
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Journal article (peer-reviewed)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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| 7. |
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| 8. |
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| 9. |
- Wright, G. S., et al.
(author)
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The Mid-Infrared Instrument for the James Webb Space Telescope, II: Design and Build
- 2015
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In: Publications of the Astronomical Society of the Pacific. - : IOP Publishing. - 0004-6280 .- 1538-3873. ; 127:953, s. 595-611
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Journal article (peer-reviewed)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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| 10. |
- Elks, Cathy E, et al.
(author)
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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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In: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 42:12, s. 1077-85
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Journal article (peer-reviewed)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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| 11. |
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| 12. |
- Lu, Yingchang, et al.
(author)
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New loci for body fat percentage reveal link between adiposity and cardiometabolic disease risk
- 2016
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In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7
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Journal article (peer-reviewed)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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| 13. |
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| 14. |
- Vimaleswaran, K. S., et al.
(author)
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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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In: Plos Medicine. - : Public Library of Science (PLoS). - 1549-1676 .- 1549-1277. ; 10:2
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Journal article (peer-reviewed)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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| 15. |
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| 16. |
- Gaulton, Kyle J, et al.
(author)
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Genetic fine mapping and genomic annotation defines causal mechanisms at type 2 diabetes susceptibility loci.
- 2015
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In: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 47:12, s. 1415-1415
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Journal article (peer-reviewed)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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| 17. |
- Nikpay, Majid, et al.
(author)
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A comprehensive 1000 Genomes-based genome-wide association meta-analysis of coronary artery disease
- 2015
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In: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 47:10, s. 1121-1121
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Journal article (peer-reviewed)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. |
- Rinaldi, P., et al.
(author)
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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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In: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 952:2
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Journal article (peer-reviewed)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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| 19. |
- Vimaleswaran, Karani S, et al.
(author)
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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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In: The lancet. Diabetes & endocrinology. - 2213-8595 .- 2213-8587. ; 2:9, s. 719-29
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Journal article (peer-reviewed)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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| 20. |
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| 21. |
- Colina, L., et al.
(author)
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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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In: Astronomy and Astrophysics. - 0004-6361 .- 1432-0746. ; 673
-
Journal article (peer-reviewed)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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| 22. |
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| 23. |
- Kilpeläinen, Tuomas O, et al.
(author)
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Genetic variation near IRS1 associates with reduced adiposity and an impaired metabolic profile.
- 2011
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In: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 43:8, s. 753-60
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Journal article (peer-reviewed)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. |
- Scott, Robert A., et al.
(author)
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An Expanded Genome-Wide Association Study of Type 2 Diabetes in Europeans
- 2017
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In: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 66:11, s. 2888-2902
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Journal article (peer-reviewed)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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| 25. |
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| 26. |
- Wright, Gillian, et al.
(author)
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The Mid-infrared Instrument for JWST and Its In-flight Performance
- 2023
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In: Publications of the Astronomical Society of the Pacific. - 0004-6280 .- 1538-3873. ; 135:1046
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Journal article (peer-reviewed)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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| 27. |
- Álvarez-Márquez, J., et al.
(author)
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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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In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 671
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Journal article (peer-reviewed)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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| 28. |
- Bouchet, P., et al.
(author)
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JWST MIRI Imager Observations of Supernova SN 1987A
- 2024
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In: Astrophysical Journal. - : American Astronomical Society. - 0004-637X .- 1538-4357. ; 965:1
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Journal article (peer-reviewed)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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| 29. |
- Fransson, Claes, 1951-, et al.
(author)
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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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In: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 383:6685, s. 898-903
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Journal article (peer-reviewed)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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| 30. |
- Gottlieb, J., et al.
(author)
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Lung transplantation for acute respiratory distress syndrome: a retrospective European cohort study
- 2022
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In: European Respiratory Journal. - : European Respiratory Society (ERS). - 0903-1936 .- 1399-3003. ; 59:6
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Journal article (peer-reviewed)abstract
- Background The published experience of lung transplantation in acute respiratory distress syndrome (ARDS) is limited. The aim of this study was to investigate the contemporary results of lung transplantation attempts in ARDS in major European centres. Methods We conducted a retrospective multicentre cohort study of all patients listed for lung transplantation between 2011 and 2019. We surveyed 68 centres in 22 European countries. All patients admitted to the waitlist for lung transplantation with a diagnosis of "ARDS/pneumonia" were included. Patients without extracorporeal membrane oxygenation (ECMO) or mechanical ventilation were excluded. Patients were followed until 1 October 2020 or death. Multivariable analysis for 1-year survival after listing and lung transplantation was performed. Results 55 centres (81%) with a total transplant activity of 12438 lung transplants during the 9-year period gave feedback. 40 patients with a median age of 35 years were identified. Patients were listed for lung transplantation in 18 different centres in 10 countries. 31 patients underwent lung transplantation (0.25% of all indications) and nine patients died on the waitlist. 90% of transplanted patients were on ECMO in combination with mechanical ventilation before lung transplantation. On multivariable analysis, transplantation during 2015-2019 was independently associated with better 1-year survival after lung transplantation (OR 10.493, 95% CI 1.977-55.705; p=0.006). 16 survivors out of 23 patients with known status (70%) returned to work after lung transplantation. Conclusions Lung transplantation in highly selected ARDS patients is feasible and outcome has improved in the modem era. The selection process remains ethically and technically challenging.
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| 31. |
- Holme, Ingar, et al.
(author)
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Congestive heart failure is associated with lipoprotein components in statin-treated patients with coronary heart disease Insights from the Incremental Decrease in End points Through Aggressive Lipid Lowering Trial (IDEAL)
- 2009
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In: ATHEROSCLEROSIS. - : Elsevier BV. - 0021-9150. ; 205:2, s. 522-527
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Journal article (peer-reviewed)abstract
- Background: Very few, if any, studies have assessed the ability of apolipoproteins to predict new-onset of congestive heart failure (HF) in statin-treated patients with coronary heart disease (CHD). Aims: To employ the Incremental Decrease in End points Through Aggressive Lipid Lowering Trial (IDEAL) study database to assess the association of on-treatment lipoprotein components with prediction of HF events and to compare their predictive value with that of established risk factors such as hypertension and diabetes. Methods: We used Cox regression models to study the relationships between on-treatment levels of apolipoproteins A1 and B to subsequent HE Chi square information value from the log likelihood was used to compare the predictive value of lipoprotein components with established risk factors of HF. Findings: In the IDEAL study, on-treatment apolipoproteins proved to be associated with the occurrence of new-onset HE Variables related to low-density lipoprotein cholesterol (LDL-C) carried less predictive information than those related to high-density lipoprotein cholesterol (HDL-C), and apoA-1 was the single variable most strongly associated with HF. LDL-C was less predictive than both non-HDL-C (total cholesterol minus HDL-C) and apoB. The ratio of apoB to apoA-1 was most strongly related to HF after adjustment for potential confounders, among which diabetes had a stronger correlation with HF than did hypertension. ApoB/apoA-1 carried approximately 2.2 times more of the statistical information value than that of diabetes. Calculation of the net reclassification improvement index revealed that about 3.7% of the patients had to be reclassified into more correct categories of risk once apoB/apoA-1 was added to the adjustment factors. The reduction in risk by intensive lipid-lowering treatment as compared to usual-dose simvastatin was well predicted by the difference in apoB/apoA-1 on-treatment levels. Interpretation: The on-treatment ratio of apoB/apoA-1 was the strongest predictor of HF in CHD patients of both IDEAL treatment arms combined, mostly driven by the strong association with apoA-1, whereas LDL-C and non-HDL-C were less able to predict HF outcome. The predictive information value contained within apoB/apoA-1 was about 2.2 times more than that of diabetes. Between-treatment group differences in HF were to a significant extent explained by on-treatment differences in apoB/apoA-1, mostly through the changes in apoB. We argue therefore, on-treatment lipoprotein components contribute to the overall future risk of HF in statin-treated patients with CHD.
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| 32. |
- Iani, Edoardo, et al.
(author)
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MIDIS : JWST NIRCam and MIRI Unveil the Stellar Population Properties of Lyα Emitters and Lyman-break Galaxies at z ≃ 3–7
- 2024
-
In: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 963:2
-
Journal article (peer-reviewed)abstract
- We study the stellar population properties of 182 spectroscopically confirmed (MUSE/VLT) Lyα emitters (LAEs) and 450 photometrically selected Lyman-break galaxies (LBGs) at z = 2.8–6.7 in the Hubble Extreme Deep Field. Leveraging the combined power of Hubble Space Telescope and JWST NIRCam and MIRI observations, we analyze their rest-frame UV-through-near-IR spectral energy distributions, with MIRI playing a crucial role in robustly assessing the LAEs' stellar masses and ages. Our LAEs are low-mass objects (log10(M⋆/M⊙)≃7.5) with little or no dust extinction (E(B − V) ≃ 0.1) and a blue UV continuum slope (β ≃ −2.2). While 75% of our LAEs are young (<100 Myr), the remaining 25% have significantly older stellar populations (≥100 Myr). These old LAEs are statistically more massive, less extinct, and have lower specific star formation rate than young LAEs. Besides, they populate the plane of M⋆ versus star formation rate along the main sequence of star-forming galaxies, while young LAEs populate the starburst region. The comparison between the LAEs' properties and those of a stellar-mass-matched sample of LBGs shows no statistical difference between these objects, except for the LBGs' redder UV continuum slope and marginally larger E(B − V) values. Interestingly, 48% of the LBGs have ages <10 Myr and are classified as starbursts, but lack detectable Lyα emission. This is likely due to H i resonant scattering and/or dust-selective extinction. Overall, we find that JWST observations are crucial in determining the properties of LAEs and shedding light on their comparison with LBGs.
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| 33. |
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| 34. |
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| 35. |
- Jones, O. C., et al.
(author)
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Ejecta, Rings, and Dust in SN 1987A with JWST MIRI/MRS
- 2023
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In: Astrophysical Journal. - : American Astronomical Society. - 0004-637X .- 1538-4357. ; 958:1
-
Journal article (peer-reviewed)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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| 36. |
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| 37. |
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| 38. |
- Olsson, Anders, 1940-, et al.
(author)
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Can LDL cholesterol be too low? Possible risks of extremely low levels
- 2017
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In: Journal of Internal Medicine. - : WILEY. - 0954-6820 .- 1365-2796. ; 281:6, s. 534-553
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Research review (peer-reviewed)abstract
- Following the continuous accumulation of evidence supporting the beneficial role of reducing low-density lipoprotein cholesterol (LDL-C) levels in the treatment and prevention of atherosclerotic cardiovascular disease and its complications, therapeutic possibilities now exist to lower LDL-C to very low levels, similar to or even lower than those seen in newborns and nonhuman species. In addition to the important task of evaluating potential side effects of such treatments, the question arises whether extremely low LDL-C levels per se may provoke adverse effects in humans. In this review, we summarize information from studies of human cellular and organ physiology, phenotypic characterization of rare genetic diseases of lipid metabolism, and experience from clinical trials. Specifically, we emphasize the importance of the robustness of the regulatory systems that maintain balanced fluxes and levels of cholesterol at both cellular and organismal levels. Even at extremely low LDL-C levels, critical capacities of steroid hormone and bile acid production are preserved, and the presence of a cholesterol blood-brain barrier protects cells in the central nervous system. Apparent relationships sometimes reported between less pronounced low LDL-C levels and disease states such as cancer, depression, infectious disease and others can generally be explained as secondary phenomena. Drug-related side effects including an increased propensity for development of type 2 diabetes occur during statin treatment, whilst further evaluation of more potent LDL-lowering treatments such as PCSK9 inhibitors is needed. Experience from the recently reported and ongoing large event-driven trials are of great interest, and further evaluation including careful analysis of cognitive functions will be important. This is an article from the symposium: Risks and benefits of Extremely Low LDL Cholesterol.
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| 39. |
- Paronen, M, et al.
(author)
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Preparation of proton-conducting membranes by direct sulfonation. 1. Effect of radicals and radical decay on the sulfonation of poly(vinyl fluoride) films
- 2003
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In: Chemistry of Materials. - : American Chemical Society (ACS). - 1520-5002 .- 0897-4756. ; 15:23, s. 4447-4455
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Journal article (peer-reviewed)abstract
- The effect of irradiation treatment on the structure and sulfonation reactivity of polyvinyl fluoride (PVF) films was studied mainly with EPR and IR spectroscopy. The main radical species produced by electron irradiation are aliphatic radicals, whereas proton irradiation creates a significant amount of polyenyl radicals. The half-life time of the aliphatic radicals was about 6 h. FTIR study shows that sulfonation reaction of PVF is a single-stage process and thus the formed sulfonic acid structures do not react further and produce new structures. In addition, it is independent of the irradiation treatment. Despite the careful synthesis and removal of O 2 from the sulfonation solution, the most important side reaction produced by the sulfonation is the formation of C=O functionalities. Irradiation treatment increases the C=O content. Both the sulfonation time and sulfonation reagent concentration demonstrate similar linear correlation with the extent of oxidation. Therefore, the oxidation cannot be decreased by means of optimizing these variables. The only important factor allowing adjustment of the structure of the final membranes is the type of irradiation and radical decay in the case of proton irradiation. Irradiation with either electrons or protons did not increase the ion exchange capacity as measured with a titrimetric method. IR study of the samples showed, however, indication of the formation of derivates of sulfonic acid in the proton-irradiated samples containing radicals.
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| 40. |
- Perez-Gonzalez, Pablo G., et al.
(author)
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Life beyond 30 : Probing the-20 < M (UV) <-17 Luminosity Function at 8 < z < 13 with the NIRCam Parallel Field of the MIRI Deep Survey
- 2023
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In: Astrophysical Journal Letters. - 2041-8205 .- 2041-8213. ; 951:1
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Journal article (peer-reviewed)abstract
- We present the ultraviolet luminosity function and an estimate of the cosmic star formation rate density at 8 < z < 13 derived from deep NIRCam observations taken in parallel with the MIRI Deep Survey of the Hubble Ultra Deep Field (HUDF), NIRCam covering the parallel field 2. Our deep (40 hr) NIRCam observations reach an F277W magnitude of 30.8 (5 & sigma;), more than 2 mag deeper than JWST public data sets already analyzed to find high-redshift galaxies. We select a sample of 44 z > 8 galaxy candidates based on their dropout nature in the F115W and/or F150W filters, a high probability for their photometric redshifts, estimated with three different codes, being at z > 8, good fits based on & chi; (2) calculations, and predominant solutions compared to z < 8 alternatives. We find mild evolution in the luminosity function from z & SIM; 13 to z & SIM; 8, i.e., only a small increase in the average number density of & SIM;0.2 dex, while the faint-end slope and absolute magnitude of the knee remain approximately constant, with values & alpha; = - 2.2 & PLUSMN; 0.1, and M * = - 20.8 & PLUSMN; 0.2 mag. Comparing our results with the predictions of state-of-the-art galaxy evolution models, we find two main results: (1) a slower increase with time in the cosmic star formation rate density compared to a steeper rise predicted by models; (2) nearly a factor of 10 higher star formation activity concentrated in scales around 2 kpc in galaxies with stellar masses & SIM;10(8) M (& ODOT;) during the first 350 Myr of the universe, z & SIM; 12, with models matching better the luminosity density observational estimations & SIM;150 Myr later, by z & SIM; 9.
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| 41. |
- Persson, K. I., et al.
(author)
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Motivators and barriers for HIV testing among men who have sex with men in Sweden
- 2016
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In: Journal of Clinical Nursing. - : Wiley. - 0962-1067 .- 1365-2702. ; 25:23-24, s. 3605-3618
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Journal article (peer-reviewed)abstract
- Aims and objectives: To explore motivators and barriers to HIV testing and to assess the factors associated with testing among men who have sex with men. Background: Previous research has considered fear, worries and structural barriers as hindrances to HIV testing among men who have sex with men. However, few studies have included assessments of actual HIV testing when exploring barriers or motivators for such testing. Design: The design of the study was a stratified cross-sectional online survey (n=2373). Method: Factor analysis was conducted to analyse the barriers and motivators for HIV testing. Logistic regression analysis was conducted to assess predictors for HIV testing. Results: Many men who have sex with men test for HIV regularly, and specific reasons for testing were having unprotected sex or starting/ending a relationship. A lack of awareness and a perception of being at low risk for exposure were common reasons for never being tested. Fear and anxiety as well as barriers related to the use of test services remain important hindrances for testing. Predictors associated with having been tested within the past 12months were: younger age (15–25years old compared with 47+); knowledge on where to take an HIV test on short notice as well as having talked with a counsellor, having received condoms for free, or having had unprotected anal intercourse with casual partners within the last 12months. Conclusion: Easily accessible test services offering testing and counselling on short notice should be available for all men who have sex with men. Outreach activities, distribution of free condoms and testing at venues where men who have sex with men meet are important prevention add-ons that can contribute to increased awareness about HIV and testing. Relevance to clinical practice: Test services must ensure confidentiality and health care professionals who meet men who have sex with men for testing need competency with regards to men who have sex with men sexual health needs. © 2016 John Wiley & Sons Ltd
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| 42. |
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| 43. |
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| 44. |
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| 45. |
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| 46. |
- Strandberg, Timo E, et al.
(author)
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Comparative Effect of Atorvastatin (80 mg) Versus Simvastatin (20 to 40 mg) in Preventing Hospitalizations for Heart Failure in Patients With Previous Myocardial Infarction
- 2009
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In: AMERICAN JOURNAL OF CARDIOLOGY. - : Elsevier BV. - 0002-9149. ; 103:10, s. 1381-1385
-
Journal article (peer-reviewed)abstract
- We investigated whether intensive cholesterol lowering could more effectively prevent heart failure (HF) in secondary prevention. The IDEAL study was a 4.8-year prospective, randomized trial comparing "usual" simvastatin treatment (20 to 40 mg/day, n = 4,449) with high-dose atorvastatin (80 mg/day, n = 4,439) in patients with a history of myocardial infarction (MI). At baseline, 94% of patients (n = 8,351) had no history of HF. During the course of the trial, there were 222 new or recurrent hospitalizations for HF (57 and 165 in those with and without HF at baseline, respectively), 123 (2.8%) in the simvastatin group and 99 (2.2%) in the atorvastatin group (hazard ratio [HR] 0.81, 95% confidence interval [CI] 0.62 to 1.05, p = 0.11). After adjustments, atorvastatin 80 mg was associated with a 26% decrease of new HF events compared with simvastatin 20 to 40 mg (HR 0.74, 95% CI 0.57 to 0.97, p = 0.03). Atorvastatin tended to be associated with fewer HF events in those with HF at baseline (n = 537, HR 0.65, 95% CI 0.38 to 1.11, p = 0.11) and those without HF at baseline (n = 8,351, HR 0.80, 95% CI 0.59 to 1.09, p = 0.15). Also, HF without preceding MI (n = 187) was decreased (HR 0.73, 95% CI 0.54 to 0.97, p = 0.03). In conclusion, atorvastatin 80 mg was more efficient than simvastatin 20 to 40 mg in preventing development of HF in patients with previous MI.
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| 47. |
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| 48. |
- van, der Steeg W.A., et al.
(author)
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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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In: Journal of the American College of Cardiology. - : Elsevier BV. - 0735-1097 .- 1558-3597. ; 51:6, s. 634-642
-
Journal article (peer-reviewed)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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| 49. |
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