| 1. |
- Roselli, Carolina, et al.
(författare)
-
Multi-ethnic genome-wide association study for atrial fibrillation
- 2018
-
Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 50:9, s. 1225-1233
-
Tidskriftsartikel (refereegranskat)abstract
- Atrial fibrillation (AF) affects more than 33 million individuals worldwide(1) and has a complex heritability(2). We conducted the largest meta-analysis of genome-wide association studies (GWAS) for AF to date, consisting of more than half a million individuals, including 65,446 with AF. In total, we identified 97 loci significantly associated with AF, including 67 that were novel in a combined-ancestry analysis, and 3 that were novel in a European-specific analysis. We sought to identify AF-associated genes at the GWAS loci by performing RNA-sequencing and expression quantitative trait locus analyses in 101 left atrial samples, the most relevant tissue for AF. We also performed transcriptome-wide analyses that identified 57 AF-associated genes, 42 of which overlap with GWAS loci. The identified loci implicate genes enriched within cardiac developmental, electrophysiological, contractile and structural pathways. These results extend our understanding of the biological pathways underlying AF and may facilitate the development of therapeutics for AF.
|
|
| 2. |
- Backes, Claudia, et al.
(författare)
-
Production and processing of graphene and related materials
- 2020
-
Ingår i: 2D Materials. - : IOP Publishing. - 2053-1583. ; 7:2
-
Tidskriftsartikel (refereegranskat)abstract
- We present an overview of the main techniques for production and processing of graphene and related materials (GRMs), as well as the key characterization procedures. We adopt a 'hands-on' approach, providing practical details and procedures as derived from literature as well as from the authors' experience, in order to enable the reader to reproduce the results. Section I is devoted to 'bottom up' approaches, whereby individual constituents are pieced together into more complex structures. We consider graphene nanoribbons (GNRs) produced either by solution processing or by on-surface synthesis in ultra high vacuum (UHV), as well carbon nanomembranes (CNM). Production of a variety of GNRs with tailored band gaps and edge shapes is now possible. CNMs can be tuned in terms of porosity, crystallinity and electronic behaviour. Section II covers 'top down' techniques. These rely on breaking down of a layered precursor, in the graphene case usually natural crystals like graphite or artificially synthesized materials, such as highly oriented pyrolythic graphite, monolayers or few layers (FL) flakes. The main focus of this section is on various exfoliation techniques in a liquid media, either intercalation or liquid phase exfoliation (LPE). The choice of precursor, exfoliation method, medium as well as the control of parameters such as time or temperature are crucial. A definite choice of parameters and conditions yields a particular material with specific properties that makes it more suitable for a targeted application. We cover protocols for the graphitic precursors to graphene oxide (GO). This is an important material for a range of applications in biomedicine, energy storage, nanocomposites, etc. Hummers' and modified Hummers' methods are used to make GO that subsequently can be reduced to obtain reduced graphene oxide (RGO) with a variety of strategies. GO flakes are also employed to prepare three-dimensional (3d) low density structures, such as sponges, foams, hydro- or aerogels. The assembly of flakes into 3d structures can provide improved mechanical properties. Aerogels with a highly open structure, with interconnected hierarchical pores, can enhance the accessibility to the whole surface area, as relevant for a number of applications, such as energy storage. The main recipes to yield graphite intercalation compounds (GICs) are also discussed. GICs are suitable precursors for covalent functionalization of graphene, but can also be used for the synthesis of uncharged graphene in solution. Degradation of the molecules intercalated in GICs can be triggered by high temperature treatment or microwave irradiation, creating a gas pressure surge in graphite and exfoliation. Electrochemical exfoliation by applying a voltage in an electrolyte to a graphite electrode can be tuned by varying precursors, electrolytes and potential. Graphite electrodes can be either negatively or positively intercalated to obtain GICs that are subsequently exfoliated. We also discuss the materials that can be amenable to exfoliation, by employing a theoretical data-mining approach. The exfoliation of LMs usually results in a heterogeneous dispersion of flakes with different lateral size and thickness. This is a critical bottleneck for applications, and hinders the full exploitation of GRMs produced by solution processing. The establishment of procedures to control the morphological properties of exfoliated GRMs, which also need to be industrially scalable, is one of the key needs. Section III deals with the processing of flakes. (Ultra)centrifugation techniques have thus far been the most investigated to sort GRMs following ultrasonication, shear mixing, ball milling, microfluidization, and wet-jet milling. It allows sorting by size and thickness. Inks formulated from GRM dispersions can be printed using a number of processes, from inkjet to screen printing. Each technique has specific rheological requirements, as well as geometrical constraints. The solvent choice is critical, not only for the GRM stability, but also in terms of optimizing printing on different substrates, such as glass, Si, plastic, paper, etc, all with different surface energies. Chemical modifications of such substrates is also a key step. Sections IV-VII are devoted to the growth of GRMs on various substrates and their processing after growth to place them on the surface of choice for specific applications. The substrate for graphene growth is a key determinant of the nature and quality of the resultant film. The lattice mismatch between graphene and substrate influences the resulting crystallinity. Growth on insulators, such as SiO2, typically results in films with small crystallites, whereas growth on the close-packed surfaces of metals yields highly crystalline films. Section IV outlines the growth of graphene on SiC substrates. This satisfies the requirements for electronic applications, with well-defined graphene-substrate interface, low trapped impurities and no need for transfer. It also allows graphene structures and devices to be measured directly on the growth substrate. The flatness of the substrate results in graphene with minimal strain and ripples on large areas, allowing spectroscopies and surface science to be performed. We also discuss the surface engineering by intercalation of the resulting graphene, its integration with Si-wafers and the production of nanostructures with the desired shape, with no need for patterning. Section V deals with chemical vapour deposition (CVD) onto various transition metals and on insulators. Growth on Ni results in graphitized polycrystalline films. While the thickness of these films can be optimized by controlling the deposition parameters, such as the type of hydrocarbon precursor and temperature, it is difficult to attain single layer graphene (SLG) across large areas, owing to the simultaneous nucleation/growth and solution/precipitation mechanisms. The differing characteristics of polycrystalline Ni films facilitate the growth of graphitic layers at different rates, resulting in regions with differing numbers of graphitic layers. High-quality films can be grown on Cu. Cu is available in a variety of shapes and forms, such as foils, bulks, foams, thin films on other materials and powders, making it attractive for industrial production of large area graphene films. The push to use CVD graphene in applications has also triggered a research line for the direct growth on insulators. The quality of the resulting films is lower than possible to date on metals, but enough, in terms of transmittance and resistivity, for many applications as described in section V. Transfer technologies are the focus of section VI. CVD synthesis of graphene on metals and bottom up molecular approaches require SLG to be transferred to the final target substrates. To have technological impact, the advances in production of high-quality large-area CVD graphene must be commensurate with those on transfer and placement on the final substrates. This is a prerequisite for most applications, such as touch panels, anticorrosion coatings, transparent electrodes and gas sensors etc. New strategies have improved the transferred graphene quality, making CVD graphene a feasible option for CMOS foundries. Methods based on complete etching of the metal substrate in suitable etchants, typically iron chloride, ammonium persulfate, or hydrogen chloride although reliable, are time- and resource-consuming, with damage to graphene and production of metal and etchant residues. Electrochemical delamination in a low-concentration aqueous solution is an alternative. In this case metallic substrates can be reused. Dry transfer is less detrimental for the SLG quality, enabling a deterministic transfer. There is a large range of layered materials (LMs) beyond graphite. Only few of them have been already exfoliated and fully characterized. Section VII deals with the growth of some of these materials. Amongst them, h-BN, transition metal tri- and di-chalcogenides are of paramount importance. The growth of h-BN is at present considered essential for the development of graphene in (opto) electronic applications, as h-BN is ideal as capping layer or substrate. The interesting optical and electronic properties of TMDs also require the development of scalable methods for their production. Large scale growth using chemical/physical vapour deposition or thermal assisted conversion has been thus far limited to a small set, such as h-BN or some TMDs. Heterostructures could also be directly grown. Section VIII discusses advances in GRM functionalization. A broad range of organic molecules can be anchored to the sp(2) basal plane by reductive functionalization. Negatively charged graphene can be prepared in liquid phase (e.g. via intercalation chemistry or electrochemically) and can react with electrophiles. This can be achieved both in dispersion or on substrate. The functional groups of GO can be further derivatized. Graphene can also be noncovalently functionalized, in particular with polycyclic aromatic hydrocarbons that assemble on the sp(2) carbon network by pi-pi stacking. In the liquid phase, this can enhance the colloidal stability of SLG/FLG. Approaches to achieve noncovalent on-substrate functionalization are also discussed, which can chemically dope graphene. Research efforts to derivatize CNMs are also summarized, as well as novel routes to selectively address defect sites. In dispersion, edges are the most dominant defects and can be covalently modified. This enhances colloidal stability without modifying the graphene basal plane. Basal plane point defects can also be modified, passivated and healed in ultra-high vacuum. The decoration of graphene with metal nanoparticles (NPs) has also received considerable attention, as it allows to exploit synergistic effects between NPs and graphene. Decoration can be either achieved chemically or in the gas phase. All LMs,
|
|
| 3. |
- Clark, Christopher E., et al.
(författare)
-
Associations Between Systolic Interarm Differences in Blood Pressure and Cardiovascular Disease Outcomes and Mortality : Individual Participant Data Meta-Analysis, Development and Validation of a Prognostic Algorithm: The INTERPRESS-IPD Collaboration
- 2021
-
Ingår i: Hypertension. - 1524-4563. ; 77:2, s. 650-661
-
Tidskriftsartikel (refereegranskat)abstract
- Systolic interarm differences in blood pressure have been associated with all-cause mortality and cardiovascular disease. We undertook individual participant data meta-analyses to (1) quantify independent associations of systolic interarm difference with mortality and cardiovascular events; (2) develop and validate prognostic models incorporating interarm difference, and (3) determine whether interarm difference remains associated with risk after adjustment for common cardiovascular risk scores. We searched for studies recording bilateral blood pressure and outcomes, established agreements with collaborating authors, and created a single international dataset: the Inter-arm Blood Pressure Difference - Individual Participant Data (INTERPRESS-IPD) Collaboration. Data were merged from 24 studies (53 827 participants). Systolic interarm difference was associated with all-cause and cardiovascular mortality: continuous hazard ratios 1.05 (95% CI, 1.02-1.08) and 1.06 (95% CI, 1.02-1.11), respectively, per 5 mm Hg systolic interarm difference. Hazard ratios for all-cause mortality increased with interarm difference magnitude from a ≥5 mm Hg threshold (hazard ratio, 1.07 [95% CI, 1.01-1.14]). Systolic interarm differences per 5 mm Hg were associated with cardiovascular events in people without preexisting disease, after adjustment for Atherosclerotic Cardiovascular Disease (hazard ratio, 1.04 [95% CI, 1.00-1.08]), Framingham (hazard ratio, 1.04 [95% CI, 1.01-1.08]), or QRISK cardiovascular disease risk algorithm version 2 (QRISK2) (hazard ratio, 1.12 [95% CI, 1.06-1.18]) cardiovascular risk scores. Our findings confirm that systolic interarm difference is associated with increased all-cause mortality, cardiovascular mortality, and cardiovascular events. Blood pressure should be measured in both arms during cardiovascular assessment. A systolic interarm difference of 10 mm Hg is proposed as the upper limit of normal. Registration: URL: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42015031227.
|
|
| 4. |
|
|
| 5. |
|
|
| 6. |
|
|
| 7. |
- Su, Zhan, et al.
(författare)
-
Common variants at the MHC locus and at chromosome 16q24.1 predispose to Barrett's esophagus.
- 2012
-
Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 44:10
-
Tidskriftsartikel (refereegranskat)abstract
- Barrett's esophagus is an increasingly common disease that is strongly associated with reflux of stomach acid and usually a hiatus hernia, and it strongly predisposes to esophageal adenocarcinoma (EAC), a tumor with a very poor prognosis. We report the first genome-wide association study on Barrett's esophagus, comprising 1,852 UK cases and 5,172 UK controls in the discovery stage and 5,986 cases and 12,825 controls in the replication stage. Variants at two loci were associated with disease risk: chromosome 6p21, rs9257809 (Pcombined=4.09×10(-9); odds ratio (OR)=1.21, 95% confidence interval (CI)=1.13-1.28), within the major histocompatibility complex locus, and chromosome 16q24, rs9936833 (Pcombined=2.74×10(-10); OR=1.14, 95% CI=1.10-1.19), for which the closest protein-coding gene is FOXF1, which is implicated in esophageal development and structure. We found evidence that many common variants of small effect contribute to genetic susceptibility to Barrett's esophagus and that SNP alleles predisposing to obesity also increase risk for Barrett's esophagus.
|
|
| 8. |
|
|
| 9. |
- Ameen, Carly, et al.
(författare)
-
Specialized sledge dogs accompanied Inuit dispersal across the North American Arctic
- 2019
-
Ingår i: Proceedings of the Royal Society of London. Biological Sciences. - : The Royal Society. - 0962-8452 .- 1471-2954. ; 286:1916
-
Tidskriftsartikel (refereegranskat)abstract
- Domestic dogs have been central to life in the North American Arctic for millennia. The ancestors of the Inuit were the first to introduce the widespread usage of dog sledge transportation technology to the Americas, but whether the Inuit adopted local Palaeo-Inuit dogs or introduced a new dog population to the region remains unknown. To test these hypotheses, we generated mitochondrial DNA and geometric morphometric data of skull and dental elements from a total of 922 North American Arctic dogs and wolves spanning over 4500 years. Our analyses revealed that dogs from Inuit sites dating from 2000 BP possess morphological and genetic signatures that distinguish them from earlier Palaeo-Inuit dogs, and identified a novel mitochondrial clade in eastern Siberia and Alaska. The genetic legacy of these Inuit dogs survives today in modern Arctic sledge dogs despite phenotypic differences between archaeological and modern Arctic dogs. Together, our data reveal that Inuit dogs derive from a secondary pre-contact migration of dogs distinct from Palaeo-Inuit dogs, and probably aided the Inuit expansion across the North American Arctic beginning around 1000 BP.
|
|
| 10. |
|
|
