| 1. |
- Glasbey, JC, et al.
(författare)
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- 2021
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swepub:Mat__t
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| 2. |
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| 7. |
- Franceschini, N., et al.
(författare)
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GWAS and colocalization analyses implicate carotid intima-media thickness and carotid plaque loci in cardiovascular outcomes
- 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
- Carotid artery intima media thickness (cIMT) and carotid plaque are measures of subclinical atherosclerosis associated with ischemic stroke and coronary heart disease (CHD). Here, we undertake meta-analyses of genome-wide association studies (GWAS) in 71,128 individuals for cIMT, and 48,434 individuals for carotid plaque traits. We identify eight novel susceptibility loci for cIMT, one independent association at the previously-identified PINX1 locus, and one novel locus for carotid plaque. Colocalization analysis with nearby vascular expression quantitative loci (cis-eQTLs) derived from arterial wall and metabolic tissues obtained from patients with CHD identifies candidate genes at two potentially additional loci, ADAMTS9 and LOXL4. LD score regression reveals significant genetic correlations between cIMT and plaque traits, and both cIMT and plaque with CHD, any stroke subtype and ischemic stroke. Our study provides insights into genes and tissue-specific regulatory mechanisms linking atherosclerosis both to its functional genomic origins and its clinical consequences in humans. © 2018, The Author(s).
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| 8. |
- Kaptoge, S., et al.
(författare)
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World Health Organization cardiovascular disease risk charts: revised models to estimate risk in 21 global regions
- 2019
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Ingår i: Lancet Global Health. - : Elsevier BV. - 2214-109X. ; 7:10
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Tidskriftsartikel (refereegranskat)abstract
- Background To help adapt cardiovascular disease risk prediction approaches to low-income and middle-income countries, WHO has convened an effort to develop, evaluate, and illustrate revised risk models. Here, we report the derivation, validation, and illustration of the revised WHO cardiovascular disease risk prediction charts that have been adapted to the circumstances of 21 global regions. Methods In this model revision initiative, we derived 10-year risk prediction models for fatal and non-fatal cardiovascular disease (ie, myocardial infarction and stroke) using individual participant data from the Emerging Risk Factors Collaboration. Models included information on age, smoking status, systolic blood pressure, history of diabetes, and total cholesterol. For derivation, we included participants aged 40-80 years without a known baseline history of cardiovascular disease, who were followed up until the first myocardial infarction, fatal coronary heart disease, or stroke event. We recalibrated models using age-specific and sex-specific incidences and risk factor values available from 21 global regions. For external validation, we analysed individual participant data from studies distinct from those used in model derivation. We illustrated models by analysing data on a further 123 743 individuals from surveys in 79 countries collected with the WHO STEPwise Approach to Surveillance. Findings Our risk model derivation involved 376 177 individuals from 85 cohorts, and 19 333 incident cardiovascular events recorded during 10 years of follow-up. The derived risk prediction models discriminated well in external validation cohorts (19 cohorts, 1 096 061 individuals, 25 950 cardiovascular disease events), with Harrell's C indices ranging from 0.685 (95% CI 0 . 629-0 741) to 0.833 (0 . 783-0- 882). For a given risk factor profile, we found substantial variation across global regions in the estimated 10-year predicted risk. For example, estimated cardiovascular disease risk for a 60-year-old male smoker without diabetes and with systolic blood pressure of 140 mm Hg and total cholesterol of 5 mmol/L ranged from 11% in Andean Latin America to 30% in central Asia. When applied to data from 79 countries (mostly low-income and middle-income countries), the proportion of individuals aged 40-64 years estimated to be at greater than 20% risk ranged from less than 1% in Uganda to more than 16% in Egypt. Interpretation We have derived, calibrated, and validated new WHO risk prediction models to estimate cardiovascular disease risk in 21 Global Burden of Disease regions. The widespread use of these models could enhance the accuracy, practicability, and sustainability of efforts to reduce the burden of cardiovascular disease worldwide. Copyright (C) 2019 The Author(s). Published by Elsevier Ltd.
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| 9. |
- Locke, Adam E, et al.
(författare)
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Genetic studies of body mass index yield new insights for obesity biology.
- 2015
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 518:7538, s. 197-401
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Tidskriftsartikel (refereegranskat)abstract
- Obesity is heritable and predisposes to many diseases. To understand the genetic basis of obesity better, here we conduct a genome-wide association study and Metabochip meta-analysis of body mass index (BMI), a measure commonly used to define obesity and assess adiposity, in up to 339,224 individuals. This analysis identifies 97 BMI-associated loci (P < 5 × 10(-8)), 56 of which are novel. Five loci demonstrate clear evidence of several independent association signals, and many loci have significant effects on other metabolic phenotypes. The 97 loci account for ∼2.7% of BMI variation, and genome-wide estimates suggest that common variation accounts for >20% of BMI variation. Pathway analyses provide strong support for a role of the central nervous system in obesity susceptibility and implicate new genes and pathways, including those related to synaptic function, glutamate signalling, insulin secretion/action, energy metabolism, lipid biology and adipogenesis.
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| 10. |
- Asselbergs, Folkert W., et al.
(författare)
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Large-Scale Gene-Centric Meta-analysis across 32 Studies Identifies Multiple Lipid Loci
- 2012
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Ingår i: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297. ; 91:5, s. 823-838
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies (GWASs) have identified many SNPs underlying variations in plasma-lipid levels. We explore whether additional loci associated with plasma-lipid phenotypes, such as high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), and triglycerides (TGs), can be identified by a dense gene-centric approach. Our meta-analysis of 32 studies in 66,240 individuals of European ancestry was based on the custom similar to 50,000 SNP genotyping array (the ITMAT-Broad-CARe array) covering similar to 2,000 candidate genes. SNP-lipid associations were replicated either in a cohort comprising an additional 24,736 samples or within the Global Lipid Genetic Consortium. We identified four, six, ten, and four unreported SNPs in established lipid genes for HDL-C, LDL-C, TC, and TGs, respectively. We also identified several lipid-related SNPs in previously unreported genes: DGAT2, HCAR2, GPIHBP1, PPARG, and FTO for HDL-C; SOCS3, APOH, SPTY2D1, BRCA2, and VLDLR for LDL-C; SOCS3, UGT1A1, BRCA2, UBE3B, FCGR2A, CHUK, and INSIG2 for TC; and SERPINF2, C4B, GCK, GATA4, INSR, and LPAL2 for TGs. The proportion of explained phenotypic variance in the subset of studies providing individual-level data was 9.9% for HDL-C, 9.5% for LDL-C, 10.3% for TC, and 8.0% for TGs. This large meta-analysis of lipid phenotypes with the use of a dense gene-centric approach identified multiple SNPs not previously described in established lipid genes and several previously unknown loci. The explained phenotypic variance from this approach was comparable to that from a meta-analysis of GWAS data, suggesting that a focused genotyping approach can further increase the understanding of heritability of plasma lipids.
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| 11. |
- Shungin, Dmitry, et al.
(författare)
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New genetic loci link adipose and insulin biology to body fat distribution.
- 2015
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 518:7538, s. 187-378
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Tidskriftsartikel (refereegranskat)abstract
- Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms.
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| 12. |
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| 13. |
- Jones, Gregory T., et al.
(författare)
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Meta-Analysis of Genome-Wide Association Studies for Abdominal Aortic Aneurysm Identifies Four New Disease-Specific Risk Loci
- 2017
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Ingår i: Circulation Research. - 0009-7330 .- 1524-4571. ; 120:2, s. 341-
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Tidskriftsartikel (refereegranskat)abstract
- Rationale: Abdominal aortic aneurysm (AAA) is a complex disease with both genetic and environmental risk factors. Together, 6 previously identified risk loci only explain a small proportion of the heritability of AAA. Objective: To identify additional AAA risk loci using data from all available genome-wide association studies. Methods and Results: Through a meta-analysis of 6 genome-wide association study data sets and a validation study totaling 10 204 cases and 107 766 controls, we identified 4 new AAA risk loci: 1q32.3 (SMYD2), 13q12.11 (LINC00540), 20q13.12 (near PCIF1/MMP9/ZNF335), and 21q22.2 (ERG). In various database searches, we observed no new associations between the lead AAA single nucleotide polymorphisms and coronary artery disease, blood pressure, lipids, or diabetes mellitus. Network analyses identified ERG, IL6R, and LDLR as modifiers of MMP9, with a direct interaction between ERG and MMP9. Conclusions: The 4 new risk loci for AAA seem to be specific for AAA compared with other cardiovascular diseases and related traits suggesting that traditional cardiovascular risk factor management may only have limited value in preventing the progression of aneurysmal disease.
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| 14. |
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| 15. |
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| 16. |
- Franceschini, N, et al.
(författare)
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GWAS and colocalization analyses implicate carotid intima-media thickness and carotid plaque loci in cardiovascular outcomes
- 2018
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 9:1, s. 5141-
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Tidskriftsartikel (refereegranskat)abstract
- Carotid artery intima media thickness (cIMT) and carotid plaque are measures of subclinical atherosclerosis associated with ischemic stroke and coronary heart disease (CHD). Here, we undertake meta-analyses of genome-wide association studies (GWAS) in 71,128 individuals for cIMT, and 48,434 individuals for carotid plaque traits. We identify eight novel susceptibility loci for cIMT, one independent association at the previously-identified PINX1 locus, and one novel locus for carotid plaque. Colocalization analysis with nearby vascular expression quantitative loci (cis-eQTLs) derived from arterial wall and metabolic tissues obtained from patients with CHD identifies candidate genes at two potentially additional loci, ADAMTS9 and LOXL4. LD score regression reveals significant genetic correlations between cIMT and plaque traits, and both cIMT and plaque with CHD, any stroke subtype and ischemic stroke. Our study provides insights into genes and tissue-specific regulatory mechanisms linking atherosclerosis both to its functional genomic origins and its clinical consequences in humans.
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| 17. |
- Do, Ron, et al.
(författare)
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Common variants associated with plasma triglycerides and risk for coronary artery disease
- 2013
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 45:11, s. 1345-
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Tidskriftsartikel (refereegranskat)abstract
- Triglycerides are transported in plasma by specific triglyceride-rich lipoproteins; in epidemiological studies, increased triglyceride levels correlate with higher risk for coronary artery disease (CAD). However, it is unclear whether this association reflects causal processes. We used 185 common variants recently mapped for plasma lipids (P < 5 x 10(-8) for each) to examine the role of triglycerides in risk for CAD. First, we highlight loci associated with both low-density lipoprotein cholesterol (LDL-C) and triglyceride levels, and we show that the direction and magnitude of the associations with both traits are factors in determining CAD risk. Second, we consider loci with only a strong association with triglycerides and show that these loci are also associated with CAD. Finally, in a model accounting for effects on LDL-C and/or high-density lipoprotein cholesterol (HDL-C) levels, the strength of a polymorphism's effect on triglyceride levels is correlated with the magnitude of its effect on CAD risk. These results suggest that triglyceride-rich lipoproteins causally influence risk for CAD.
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| 18. |
- Willer, Cristen J., et al.
(författare)
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Discovery and refinement of loci associated with lipid levels
- 2013
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 45:11, s. 1274-1283
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Tidskriftsartikel (refereegranskat)abstract
- Levels of low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, triglycerides and total cholesterol are heritable, modifiable risk factors for coronary artery disease. To identify new loci and refine known loci influencing these lipids, we examined 188,577 individuals using genome-wide and custom genotyping arrays. We identify and annotate 157 loci associated with lipid levels at P < 5 x 10(-8), including 62 loci not previously associated with lipid levels in humans. Using dense genotyping in individuals of European, East Asian, South Asian and African ancestry, we narrow association signals in 12 loci. We find that loci associated with blood lipid levels are often associated with cardiovascular and metabolic traits, including coronary artery disease, type 2 diabetes, blood pressure, waist-hip ratio and body mass index. Our results demonstrate the value of using genetic data from individuals of diverse ancestry and provide insights into the biological mechanisms regulating blood lipids to guide future genetic, biological and therapeutic research.
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| 19. |
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| 20. |
- Andresen, G. B., et al.
(författare)
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Evaporative Cooling of Antiprotons to Cryogenic Temperatures
- 2010
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Ingår i: Physical Review Letters. - 0031-9007 .- 1079-7114. ; 105:1, s. 013003-
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Tidskriftsartikel (refereegranskat)abstract
- We report the application of evaporative cooling to clouds of trapped antiprotons, resulting in plasmas with measured temperature as low as 9 K. We have modeled the evaporation process for charged particles using appropriate rate equations. Good agreement between experiment and theory is observed, permitting prediction of cooling efficiency in future experiments. The technique opens up new possibilities for cooling of trapped ions and is of particular interest in antiproton physics, where a precise CPT test on trapped antihydrogen is a long-standing goal.
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| 21. |
- Andresen, G. B., et al.
(författare)
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Search for trapped antihydrogen
- 2011
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Ingår i: Physics Letters B. - : Elsevier BV. - 0370-2693 .- 1873-2445. ; 695:1-4, s. 95-104
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Tidskriftsartikel (refereegranskat)abstract
- We present the results of an experiment to search for trapped antihydrogen atoms with the ALPHA antihydrogen trap at the CERN Antiproton Decelerator. Sensitive diagnostics of the temperatures, sizes, and densities of the trapped antiproton and positron plasmas have been developed, which in turn permitted development of techniques to precisely and reproducibly control the initial experimental parameters. The use of a position-sensitive annihilation vertex detector, together with the capability of controllably quenching the superconducting magnetic minimum trap, enabled us to carry out a high-sensitivity and low-background search for trapped synthesised antihydrogen atoms. We aim to identify the annihilations of antihydrogen atoms held for at least 130 ms in the trap before being released over ~30 ms. After a three-week experimental run in 2009 involving mixing of 107 antiprotons with 1.3ￜ109 positrons to produce 6ￜ105 antihydrogen atoms, we have identified six antiproton annihilation events that are consistent with the release of trapped antihydrogen. The cosmic ray background, estimated to contribute 0.14 counts, is incompatible with this observation at a significance of 5.6 sigma. Extensive simulations predict that an alternative source of annihilations, the escape of mirror-trapped antiprotons, is highly unlikely, though this possibility has not yet been ruled out experimentally.
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| 22. |
- Charlton, M, et al.
(författare)
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Antiparticle sources for antihydrogen production and trapping
- 2011
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Ingår i: Journal of Physics: Conference Series. - : IOP Publishing. - 1742-6596. ; 262, s. 012001-
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Tidskriftsartikel (refereegranskat)abstract
- Sources of positrons and antiprotons that are currently used for the formation of antihydrogen with low kinetic energies are reviewed, mostly in the context of the ALPHA collaboration and its predecessor ATHENA. The experiments were undertaken at the Antiproton Decelerator facility, which is located at CERN. Operations performed on the clouds of antiparticles to facilitate their mixing to produce antihydrogen are described. These include accumulation, cooling and manipulation. The formation of antihydrogen and some of the characteristics of the anti-atoms that are created are discussed. Prospects for trapping antihydrogen in a magnetic minimum trap, as envisaged by the ALPHA collaboration, are reviewed.
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| 23. |
- Johnson, Toby, et al.
(författare)
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Blood Pressure Loci Identified with a Gene-Centric Array.
- 2011
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Ingår i: American Journal of Human Genetics. - : Elsevier BV. - 1537-6605 .- 0002-9297. ; 89:6, s. 688-700
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Tidskriftsartikel (refereegranskat)abstract
- Raised blood pressure (BP) is a major risk factor for cardiovascular disease. Previous studies have identified 47 distinct genetic variants robustly associated with BP, but collectively these explain only a few percent of the heritability for BP phenotypes. To find additional BP loci, we used a bespoke gene-centric array to genotype an independent discovery sample of 25,118 individuals that combined hypertensive case-control and general population samples. We followed up four SNPs associated with BP at our p < 8.56× 10(-7) study-specific significance threshold and six suggestively associated SNPs in a further 59,349 individuals. We identified and replicated a SNP at LSP1/TNNT3, a SNP at MTHFR-NPPB independent (r(2) = 0.33) of previous reports, and replicated SNPs at AGT and ATP2B1 reported previously. An analysis of combined discovery and follow-up data identified SNPs significantly associated with BP at p < 8.56× 10(-7) at four further loci (NPR3, HFE, NOS3, and SOX6). The high number of discoveries made with modest genotyping effort can be attributed to using a large-scale yet targeted genotyping array and to the development of a weighting scheme that maximized power when meta-analyzing results from samples ascertained with extreme phenotypes, in combination with results from nonascertained or population samples. Chromatin immunoprecipitation and transcript expression data highlight potential gene regulatory mechanisms at the MTHFR and NOS3 loci. These results provide candidates for further study to help dissect mechanisms affecting BP and highlight the utility of studying SNPs and samples that are independent of those studied previously even when the sample size is smaller than that in previous studies.
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| 24. |
- Madsen, N, et al.
(författare)
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Search for trapped antihydrogen in ALPHA
- 2011
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Ingår i: Canadian journal of physics (Print). - 0008-4204 .- 1208-6045. ; 89:1, s. 7-16
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Tidskriftsartikel (refereegranskat)abstract
- Antihydrogen spectroscopy promises precise tests of the symmetry of matter and antimatter, and can possibly offer new insights into the baryon asymmetry of the universe. Antihydrogen is, however, difficult to synthesize and is produced only in small quantities. The ALPHA collaboration is therefore pursuing a path towards trapping cold antihydrogen to permit the use of precision atomic physics tools to carry out comparisons of antihydrogen and hydrogen. ALPHA has addressed these challenges. Control of the plasma sizes has helped to lower the influence of the multipole field used in the neutral atom trap, and thus lowered the temperature of the created atoms. Finally, the first systematic attempt to identify trapped antihydrogen in our system is discussed. This discussion includes special techniques for fast release of the trapped anti-atoms, as well as a silicon vertex detector to identify antiproton annihilations. The silicon detector reduces the background of annihilations, including background from antiprotons that can be mirror trapped in the fields of the neutral atom trap. A description of how to differentiate between these events and those resulting from trapped antihydrogen atoms is also included.
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| 25. |
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| 26. |
- 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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| 27. |
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| 28. |
- Van Der Werf, D. P., et al.
(författare)
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Antimatter transport processes
- 2010
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Ingår i: AAPS Journal. - : IOP Publishing. - 1550-7416. ; 257:1
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Tidskriftsartikel (refereegranskat)abstract
- A comparison of the 1S-2S transitions of hydrogen and antihydrogen will yield a stringent test of CPT conservation. Necessarily, the antihydrogen atoms need to be trapped to perform high precision spectroscopy measurements. Therefore, an approximately 0.75 T deep neutral atom trap, equivalent to about 0.5 K for ground state (anti)hydrogen atoms, has been superimposed on a Penning-Malmberg trap in which the anti-atoms are formed. The antihydrogen atoms are produced following a number of steps. A bunch of antiprotons from the CERN Antiproton Decelerator is caught in a Penning-Malmberg trap and subsequently sympathetically cooled and then compressed using rotating wall electric fields. A positron plasma, formed in a separate accumulator, is transported to the main system and also compressed. Antihydrogen atoms are then formed by mixing the antiprotons and positrons. The velocity of the anti-atoms, and their binding energies, will strongly depend on the initial conditions of the constituent particles, for example their temperatures and densities, and on the details of the mixing process. In this paper the complete lifecycle of antihydrogen atoms will be presented, starting with the production of the constituent antiparticles and the description of the manipulations necessary to prepare them appropriately for antihydrogen formation. The latter will also be described, as will the possible fates of the anti-atoms.
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| 29. |
- Amole, C., et al.
(författare)
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The ALPHA antihydrogen trapping apparatus
- 2014
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Ingår i: Nuclear Instruments and Methods in Physics Research Section A. - : Elsevier BV. - 0168-9002 .- 1872-9576. ; 735, s. 319-340
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Tidskriftsartikel (refereegranskat)abstract
- The ALPHA collaboration, based at CERN, has recently succeeded in confining cold antihydrogen atoms in a magnetic minimum neutral atom trap and has performed the first study of a resonant transition of the anti-atoms. The ALPHA apparatus will be described herein, with emphasis on the structural aspects, diagnostic methods and techniques that have enabled antihydrogen trapping and experimentation to be achieved.
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| 30. |
- Andresen, G. B., et al.
(författare)
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Antihydrogen annihilation reconstruction with the ALPHA silicon detector
- 2012
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Ingår i: Nuclear Instruments and Methods in Physics Research Section A. - : Elsevier BV. - 0168-9002 .- 1872-9576. ; 684, s. 73-81
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Tidskriftsartikel (refereegranskat)abstract
- The ALPHA experiment has succeeded in trapping antihydrogen, a major milestone on the road to spectroscopic comparisons of antihydrogen with hydrogen. An annihilation vertex detector, which determines the time and position of antiproton annihilations, has been central to this achievement. This detector, an array of double-sided silicon microstrip detector modules arranged in three concentric cylindrical tiers, is sensitive to the passage of charged particles resulting from antiproton annihilation. This article describes the method used to reconstruct the annihilation location and to distinguish the annihilation signal from the cosmic ray background. Recent experimental results using this detector are outlined.
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| 31. |
- Andresen, G. B., et al.
(författare)
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Confinement of antihydrogen for 1,000 seconds
- 2011
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Ingår i: Nature Physics. - 1745-2473 .- 1745-2481. ; 7:7, s. 558-564
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Tidskriftsartikel (refereegranskat)abstract
- Atoms made of a particle and an antiparticle are unstable, usually surviving less than a microsecond. Antihydrogen, made entirely of antiparticles, is believed to be stable, and it is this longevity that holds the promise of precision studies of matter-antimatter symmetry. We have recently demonstrated trapping of antihydrogen atoms by releasing them after a confinement time of 172 ms. A critical question for future studies is: how long can anti-atoms be trapped? Here, we report the observation of anti-atom confinement for 1,000 s, extending our earlier results by nearly four orders of magnitude. Our calculations indicate that most of the trapped anti-atoms reach the ground state. Further, we report the first measurement of the energy distribution of trapped antihydrogen, which, coupled with detailed comparisons with simulations, provides a key tool for the systematic investigation of trapping dynamics. These advances open up a range of experimental possibilities, including precision studies of charge-parity-time reversal symmetry and cooling to temperatures where gravitational effects could become apparent.
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| 32. |
- Burgess, S., et al.
(författare)
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Bayesian methods for meta-analysis of causal relationships estimated using genetic instrumental variables
- 2010
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Ingår i: Statistics in medicine. - : Wiley. - 1097-0258 .- 0277-6715. ; 29:12, s. 1298-311
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Tidskriftsartikel (refereegranskat)abstract
- Genetic markers can be used as instrumental variables, in an analogous way to randomization in a clinical trial, to estimate the causal relationship between a phenotype and an outcome variable. Our purpose is to extend the existing methods for such Mendelian randomization studies to the context of multiple genetic markers measured in multiple studies, based on the analysis of individual participant data. First, for a single genetic marker in one study, we show that the usual ratio of coefficients approach can be reformulated as a regression with heterogeneous error in the explanatory variable. This can be implemented using a Bayesian approach, which is next extended to include multiple genetic markers. We then propose a hierarchical model for undertaking a meta-analysis of multiple studies, in which it is not necessary that the same genetic markers are measured in each study. This provides an overall estimate of the causal relationship between the phenotype and the outcome, and an assessment of its heterogeneity across studies. As an example, we estimate the causal relationship of blood concentrations of C-reactive protein on fibrinogen levels using data from 11 studies. These methods provide a flexible framework for efficient estimation of causal relationships derived from multiple studies. Issues discussed include weak instrument bias, analysis of binary outcome data such as disease risk, missing genetic data, and the use of haplotypes.
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| 33. |
- Butler, E., et al.
(författare)
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Towards antihydrogen trapping and spectroscopy at ALPHA
- 2011
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Ingår i: Hyperfine Interactions. - : Springer Science and Business Media LLC. - 0304-3843 .- 1572-9540. ; 199:1, s. 39-48
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Tidskriftsartikel (refereegranskat)abstract
- Spectroscopy of antihydrogen has the potential to yield high-precision tests of the CPT theorem and shed light on the matter-antimatter imbalance in the Universe. The ALPHA antihydrogen trap at CERN’s Antiproton Decelerator aims to prepare a sample of antihydrogen atoms confined in an octupole-based Ioffe trap and to measure the frequency of several atomic transitions. We describe our techniques to directly measure the antiproton temperature and a new technique to cool them to below 10 K. We also show how our unique position-sensitive annihilation detector provides us with a highly sensitive method of identifying antiproton annihilations and effectively rejecting the cosmic-ray background.
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| 34. |
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| 35. |
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| 36. |
- 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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| 37. |
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| 38. |
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| 39. |
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| 40. |
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| 41. |
- Amole, C., et al.
(författare)
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Discriminating between antihydrogen and mirror-trapped antiprotons in a minimum-B trap
- 2012
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Ingår i: New Journal of Physics. - : IOP Publishing. - 1367-2630. ; 14, s. 015010-
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Tidskriftsartikel (refereegranskat)abstract
- Recently, antihydrogen atoms were trapped at CERN in a magnetic minimum (minimum-B) trap formed by superconducting octupole and mirror magnet coils. The trapped antiatoms were detected by rapidly turning off these magnets, thereby eliminating the magnetic minimum and releasing any antiatoms contained in the trap. Once released, these antiatoms quickly hit the trap wall, whereupon the positrons and antiprotons in the antiatoms annihilate. The antiproton annihilations produce easily detected signals; we used these signals to prove that we trapped antihydrogen. However, our technique could be confounded by mirror-trapped antiprotons, which would produce seemingly identical annihilation signals upon hitting the trap wall. In this paper, we discuss possible sources of mirror-trapped antiprotons and show that antihydrogen and antiprotons can be readily distinguished, often with the aid of applied electric fields, by analyzing the annihilation locations and times. We further discuss the general properties of antiproton and antihydrogen trajectories in this magnetic geometry, and reconstruct the antihydrogen energy distribution from the measured annihilation time history.
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| 42. |
- Amole, C., et al.
(författare)
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Resonant quantum transitions in trapped antihydrogen atoms
- 2012
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 483:7390, s. 439-U86
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Tidskriftsartikel (refereegranskat)abstract
- The hydrogen atom is one of the most important and influential model systems in modern physics. Attempts to understand its spectrum are inextricably linked to the early history and development of quantum mechanics. The hydrogen atom's stature lies in its simplicity and in the accuracy with which its spectrum can be measured(1) and compared to theory. Today its spectrum remains a valuable tool for determining the values of fundamental constants and for challenging the limits of modern physics, including the validity of quantum electrodynamics and-by comparison with measurements on its antimatter counterpart, antihydrogen-the validity of CPT (charge conjugation, parity and time reversal) symmetry. Here we report spectroscopy of a pure antimatter atom, demonstrating resonant quantum transitions in antihydrogen. We have manipulated the internal spin state(2,3) of antihydrogen atoms so as to induce magnetic resonance transitions between hyperfine levels of the positronic ground state. We used resonant microwave radiation to flip the spin of the positron in antihydrogen atoms that were magnetically trapped(4-6) in the ALPHA apparatus. The spin flip causes trapped anti-atoms to be ejected from the trap. We look for evidence of resonant interaction by comparing the survival rate of trapped atoms irradiated with microwaves on-resonance to that of atoms subjected to microwaves that are off-resonance. In one variant of the experiment, we detect 23 atoms that survive in 110 trapping attempts with microwaves off-resonance (0.21 per attempt), and only two atoms that survive in 103 attempts with microwaves on-resonance (0.02 per attempt). We also describe the direct detection of the annihilation of antihydrogen atoms ejected by the microwaves.
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| 43. |
- Amole, C., et al.
(författare)
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Silicon vertex detector upgrade in the ALPHA experiment
- 2013
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Ingår i: Nuclear Instruments and Methods in Physics Research Section A. - : Elsevier BV. - 0168-9002 .- 1872-9576. ; 732, s. 134-136
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Tidskriftsartikel (refereegranskat)abstract
- The Silicon Vertex Detector (SVD) is the main diagnostic tool in the ALPHA-experiment. It provides precise spatial and timing information of antiproton (antihydrogen) annihilation events (vertices), and most importantly, the SVD is capable of directly identifying and analysing single annihilation events, thereby forming the basis of ALPHA's analysis. This paper describes the ALPHA SVD and its upgrade, installed in the ALPHA's new neutral atom trap.
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| 44. |
- Andresen, G. B., et al.
(författare)
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Autoresonant Excitation of Antiproton Plasmas
- 2011
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Ingår i: Physical Review Letters. - 0031-9007 .- 1079-7114. ; 106:2, s. 025002-
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Tidskriftsartikel (refereegranskat)abstract
- We demonstrate controllable excitation of the center-of-mass longitudinal motion of a thermal antiproton plasma using a swept-frequency autoresonant drive. When the plasma is cold, dense, and highly collective in nature, we observe that the entire system behaves as a single-particle nonlinear oscillator, as predicted by a recent theory. In contrast, only a fraction of the antiprotons in a warm plasma can be similarly excited. Antihydrogen was produced and trapped by using this technique to drive antiprotons into a positron plasma, thereby initiating atomic recombination
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| 45. |
- Andresen, G. B., et al.
(författare)
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The ALPHA-detector : Module Production and Assembly
- 2012
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Ingår i: Journal of Instrumentation. - 1748-0221. ; 7, s. C01051-
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Tidskriftsartikel (refereegranskat)abstract
- ALPHA is one of the experiments situated at CERN's Antiproton Decelerator (AD). A Silicon Vertex Detector (SVD) is placed to surround the ALPHA atom trap. The main purpose of the SVD is to detect and locate antiproton annihilation events by means of the emitted charged pions. The SVD system is presented with special focus given to the design, fabrication and performance of the modules.
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| 46. |
- Andresen, G. B., et al.
(författare)
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Trapped antihydrogen
- 2010
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 468:7324, s. 673-676
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Tidskriftsartikel (refereegranskat)abstract
- Antimatter was first predicted1 in 1931, by Dirac. Work with high-energy antiparticles is now commonplace, and anti-electrons are used regularly in the medical technique of positron emission tomography scanning. Antihydrogen, the bound state of an antiproton and a positron, has been produced2, 3 at low energies at CERN (the European Organization for Nuclear Research) since 2002. Antihydrogen is of interest for use in a precision test of nature’s fundamental symmetries. The charge conjugation/parity/time reversal (CPT) theorem, a crucial part of the foundation of the standard model of elementary particles and interactions, demands that hydrogen and antihydrogen have the same spectrum. Given the current experimental precision of measurements on the hydrogen atom (about two parts in 1014 for the frequency of the 1s-to-2s transition4), subjecting antihydrogen to rigorous spectroscopic examination would constitute a compelling, model-independent test of CPT. Antihydrogen could also be used to study the gravitational behaviour of antimatter5. However, so far experiments have produced antihydrogen that is not confined, precluding detailed study of its structure. Here we demonstrate trapping of antihydrogen atoms. From the interaction of about 107 antiprotons and 7 × 108 positrons, we observed 38 annihilation events consistent with the controlled release of trapped antihydrogen from our magnetic trap; the measured background is 1.4 ± 1.4 events. This result opens the door to precision measurements on anti-atoms, which can soon be subjected to the same techniques as developed for hydrogen.
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| 47. |
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| 48. |
- Cuchel, M., et al.
(författare)
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Homozygous familial hypercholesterolaemia: new insights and guidance for clinicians to improve detection and clinical management. A position paper from the Consensus Panel on Familial Hypercholesterolaemia of the European Atherosclerosis Society
- 2014
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Ingår i: European Heart Journal. - : Oxford University Press (OUP). - 0195-668X .- 1522-9645. ; 35:32
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Tidskriftsartikel (refereegranskat)abstract
- Aims Homozygous familial hypercholesterolaemia (HoFH) is a rare life-threatening condition characterized by markedly elevated circulating levels of low-density lipoprotein cholesterol (LDL-C) and accelerated, premature atherosclerotic cardiovascular disease (ACVD). Given recent insights into the heterogeneity of genetic defects and clinical phenotype of HoFH, and the availability of new therapeutic options, this Consensus Panel on Familial Hypercholesterolaemia of the European Atherosclerosis Society (EAS) critically reviewed available data with the aim of providing clinical guidance for the recognition and management of HoFH. Methods and results Early diagnosis of HoFH and prompt initiation of diet and lipid-lowering therapy are critical. Genetic testing may provide a definitive diagnosis, but if unavailable, markedly elevated LDL-C levels together with cutaneous or tendon xanthomas before 10 years, or untreated elevated LDL-C levels consistent with heterozygous FH in both parents, are suggestive of HoFH. We recommend that patients with suspected HoFH are promptly referred to specialist centres for a comprehensive ACVD evaluation and clinical management. Lifestyle intervention and maximal statin therapy are the mainstays of treatment, ideally started in the first year of life or at an initial diagnosis, often with ezetimibe and other lipid-modifying therapy. As patients rarely achieve LDL-C targets, adjunctive lipoprotein apheresis is recommended where available, preferably started by age 5 and no later than 8 years. The number of therapeutic approaches has increased following approval of lomitapide and mipomersen for HoFH. Given the severity of ACVD, we recommend regular follow-up, including Doppler echocardiographic evaluation of the heart and aorta annually, stress testing and, if available, computed tomography coronary angiography every 5 years, or less if deemed necessary. Conclusion This EAS Consensus Panel highlights the need for early identification of HoFH patients, prompt referral to specialized centres, and early initiation of appropriate treatment. These recommendations offer guidance for a wide spectrum of clinicians who are often the first to identify patients with suspected HoFH.
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| 49. |
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| 50. |
- Hegele, R. A., et al.
(författare)
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The polygenic nature of hypertriglyceridaemia: implications for definition, diagnosis, and management
- 2014
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Ingår i: Lancet Diabetes & Endocrinology. - : Elsevier BV. - 2213-8587. ; 2:8, s. 655-666
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Tidskriftsartikel (refereegranskat)abstract
- Plasma triglyceride concentration is a biomarker for circulating triglyceride-rich lipoproteins and their metabolic remnants. Common mild-to-moderate hypertriglyceridaemia is typically multigenic, and results from the cumulative burden of common and rare variants in more than 30 genes, as quantified by genetic risk scores. Rare autosomal recessive monogenic hypertriglyceridaemia can result from large-effect mutations in six different genes. Hypertriglyceridaemia is exacerbated by non-genetic factors. On the basis of recent genetic data, we redefine the disorder into two states: severe (triglyceride concentration >10 mmol/L), which is more likely to have a monogenic cause; and mild-to-moderate (triglyceride concentration 2-10 mmol/L). Because of clustering of susceptibility alleles and secondary factors in families, biochemical screening and counselling for family members is essential, but routine genetic testing is not warranted. Treatment includes management of lifestyle and secondary factors, and pharmacotherapy. In severe hypertriglyceridaemia, intervention is indicated because of pancreatitis risk; in mild-to-moderate hypertriglyceridaemia, intervention can be indicated to prevent cardiovascular disease, dependent on triglyceride concentration, concomitant lipoprotein disturbances, and overall cardiovascular risk.
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