| 451. |
- Lantz, Adam, et al.
(författare)
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Measuring the migration of surgical specialists
- 2020
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Ingår i: Surgery (United States). - : Elsevier BV. - 0039-6060 .- 1532-7361. ; 168:3, s. 550-557
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Tidskriftsartikel (refereegranskat)abstract
- Background: The lack of access to essential surgical care in low-income countries is aggravated by emigration of locally-trained surgical specialists to more affluent regions. Yet, the global diaspora of surgeons, obstetricians, and anesthesiologists from low-income and middle-income countries has never been fully described and compared with those who have remained in their country of origin. It is also unclear whether the surgical workforce is more affected by international migration than other medical specialists. In this study, we aimed to quantify the proportion of surgical specialists originating from low-income and middle-income countries that currently work in high-income countries. Methods: We retrieved surgical workforce data from 48 high-income countries and 102 low-income and middle-income countries using the database of the World Health Organization Global Surgical Workforce. We then compared this domestic workforce with more granular data on the country of initial medical qualification of all surgeons, anesthesiologists, and obstetricians made available for 14 selected high-income countries to calculate the proportion of surgical specialists working abroad. Results: We identified 1,118,804 specialist surgeons, anesthesiologists, or obstetricians from 102 low-income and middle-income countries, of whom 33,021 (3.0%) worked in the 14 included high-income countries. The proportion of surgical specialists abroad was greatest for the African and South East Asian regions (12.8% and 12.1%). The proportion of specialists abroad was not greater for surgeons, anesthesiologists, or obstetricians than for physicians and other medical specialists (P = .465). Overall, the countries with the lowest remaining density of surgical specialists were also the countries from which the largest proportion of graduates were now working in high-income countries (P = .011). Conclusion: A substantial proportion of all surgeons, anesthesiologists, and obstetricians from low-income and middle-income countries currently work in high-income countries. In addition to decreasing migration from areas of surgical need, innovative strategies to retain and strengthen the surgical workforce could involve engaging this large international pool of surgical specialists and instructors.
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| 452. |
- Li, Ni L., et al.
(författare)
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Genetic Predisposition to Multiple Myeloma at 5q15 Is Mediated by an ELL2 Enhancer Polymorphism
- 2017
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Ingår i: Cell Reports. - : Elsevier BV. - 2211-1247. ; 20:11, s. 2556-2564
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Tidskriftsartikel (refereegranskat)abstract
- Multiple myeloma (MM) is a malignancy of plasma cells. Genome-wide association studies have shown that variation at 5q15 influences MM risk. Here, we have sought to decipher the causal variant at 5q15 and the mechanism by which it influences tumorigenesis. We show that rs6877329 G > C resides in a predicted enhancer element that physically interacts with the transcription start site of ELL2. The rs6877329-C risk allele is associated with reduced enhancer activity and lowered ELL2 expression. Since ELL2 is critical to the B cell differentiation process, reduced ELL2 expression is consistent with inherited genetic variation contributing to arrest of plasma cell development, facilitating MM clonal expansion. These data provide evidence for a biological mechanism underlying a hereditary risk of MM at 5q15.
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| 453. |
- Li, Ni, et al.
(författare)
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Multiple myeloma risk variant at 7p15.3 creates an IRF4-binding site and interferes with CDCA7L expression
- 2016
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies have identified several risk loci for multiple myeloma (MM); however, the mechanisms by which they influence MM are unknown. Here by using genetic association data and functional characterization, we demonstrate that rs4487645 G>T, the most highly associated variant (P = 5.30 × 10-25), resides in an enhancer element 47 kb upstream of the transcription start site of c-Myc-interacting CDCA7L. The G-risk allele, associated with increased CDCA7L expression (P=1.95 × 10-36), increases IRF4 binding and the enhancer interacts with the CDCA7L promoter. We show that suppression of CDCA7L limits MM proliferation through apoptosis, and increased CDCA7L expression is associated with adverse patient survival. These findings implicate IRF4-mediated CDCA7L expression in MM biology and indicate how germline variation might confer susceptibility to MM.
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| 454. |
- Lu, Ru-Sen, et al.
(författare)
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Detection of Intrinsic Source Structure at similar to 3 Schwarzschild Radii with Millimeter-VLBI Observations of SAGITTARIUS A*
- 2018
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Ingår i: Astrophysical Journal. - : American Astronomical Society. - 1538-4357 .- 0004-637X. ; 859:1
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Tidskriftsartikel (refereegranskat)abstract
- We report results from very long baseline interferometric (VLBI) observations of the supermassive black hole in the Galactic center, Sgr A*, at 1.3 mm (230 GHz). The observations were performed in 2013 March using six VLBI stations in Hawaii, California, Arizona, and Chile. Compared to earlier observations, the addition of the APEX telescope in Chile almost doubles the longest baseline length in the array, provides additional uv coverage in the N-S direction, and leads to a spatial resolution of similar to 30 mu as (similar to 3 Schwarzschild radii) for Sgr A*. The source is detected even at the longest baselines with visibility amplitudes of similar to 4%-13% of the total flux density. We argue that such flux densities cannot result from interstellar refractive scattering alone, but indicate the presence of compact intrinsic source structure on scales of similar to 3 Schwarzschild radii. The measured nonzero closure phases rule out point-symmetric emission. We discuss our results in the context of simple geometric models that capture the basic characteristics and brightness distributions of disk-and jet-dominated models and show that both can reproduce the observed data. Common to these models are the brightness asymmetry, the orientation, and characteristic sizes, which are comparable to the expected size of the black hole shadow. Future 1.3 mm VLBI observations with an expanded array and better sensitivity will allow more detailed imaging of the horizon-scale structure and bear the potential for a deep insight into the physical processes at the black hole boundary.
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| 455. |
- Malhotra, Rajeev, et al.
(författare)
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HDAC9 is implicated in atherosclerotic aortic calcification and affects vascular smooth muscle cell phenotype
- 2019
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 51:11, s. 1580-
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Tidskriftsartikel (refereegranskat)abstract
- Aortic calcification is an important independent predictor of future cardiovascular events. We performed a genome-wide association meta-analysis to determine SNPs associated with the extent of abdominal aortic calcification (n = 9,417) or descending thoracic aortic calcification (n = 8,422). Two genetic loci, HDAC9 and RAP1GAP, were associated with abdominal aortic calcification at a genome-wide level (P < 5.0 × 10−8). No SNPs were associated with thoracic aortic calcification at the genome-wide threshold. Increased expression of HDAC9 in human aortic smooth muscle cells promoted calcification and reduced contractility, while inhibition of HDAC9 in human aortic smooth muscle cells inhibited calcification and enhanced cell contractility. In matrix Gla protein–deficient mice, a model of human vascular calcification, mice lacking HDAC9 had a 40% reduction in aortic calcification and improved survival. This translational genomic study identifies the first genetic risk locus associated with calcification of the abdominal aorta and describes a previously unknown role for HDAC9 in the development of vascular calcification.
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| 456. |
- Menon, Shyam H., et al.
(författare)
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The dependence of the hierarchical distribution of star clusters on galactic environment
- 2021
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Ingår i: Monthly notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 507:4, s. 5542-5566
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Tidskriftsartikel (refereegranskat)abstract
- We use the angular two-point correlation function (TPCF) to investigate the hierarchical distribution of young star clusters in 12 local (3–18 Mpc) star-forming galaxies using star cluster catalogs obtained with the Hubble Space Telescope (HST) as part of the Treasury Program Legacy ExtraGalactic UV Survey. The sample spans a range of different morphological types, allowing us to infer how the physical properties of the galaxy affect the spatial distribution of the clusters. We also prepare a range of physically motivated toy models to compare with and interpret the observed features in the TPCFs. We find that, conforming to earlier studies, young clusters (T≲10Myr) have power-law TPCFs that are characteristic of fractal distributions with a fractal dimension D2, and this scale-free nature extends out to a maximum scale lcorr beyond which the distribution becomes Poissonian. However, lcorr, and D2 vary significantly across the sample, and are correlated with a number of host galaxy physical properties, suggesting that there are physical differences in the underlying star cluster distributions. We also find that hierarchical structuring weakens with age, evidenced by flatter TPCFs for older clusters (T≳10Myr), that eventually converges to the residual correlation expected from a completely random large-scale radial distribution of clusters in the galaxy in ∼100Myr. Our study demonstrates that the hierarchical distribution of star clusters evolves with age, and is strongly dependent on the properties of the host galaxy environment.
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| 457. |
- Middleton, Steven J, et al.
(författare)
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Nav1.7 is required for normal C-low threshold mechanoreceptor function in humans and mice.
- 2022
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Ingår i: Brain : a journal of neurology. - : Oxford University Press (OUP). - 1460-2156 .- 0006-8950. ; 145:10
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Tidskriftsartikel (refereegranskat)abstract
- Patients with bi-allelic loss of function mutations in the voltage-gated sodium channel Nav1.7 present with congenital insensitivity to pain (CIP), whilst low threshold mechanosensation is reportedly normal. Using psychophysics (n = 6 CIP participants and n = 86 healthy controls) and facial EMG (n = 3 CIP participants and n = 8 healthy controls) we have found that these patients also have abnormalities in the encoding of affective touch which is mediated by the specialised afferents; C-low threshold mechanoreceptors (C-LTMRs). In the mouse we found that C-LTMRs express high levels of Nav1.7. Genetic loss or selective pharmacological inhibition of Nav1.7 in C-LTMRs resulted in a significant reduction in the total sodium current density, an increased mechanical threshold and reduced sensitivity to non-noxious cooling. The behavioural consequence of loss of Nav1.7 in C-LTMRs in mice was an elevation in the von Frey mechanical threshold and less sensitivity to cooling on a thermal gradient. Nav1.7 is therefore not only essential for normal pain perception but also for normal C-LTMR function, cool sensitivity and affective touch.
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| 458. |
- Mitchell, Jonathan S., et al.
(författare)
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Genome-wide association study identifies multiple susceptibility loci for multiple myeloma
- 2016
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7
-
Tidskriftsartikel (refereegranskat)abstract
- Multiple myeloma (MM) is a plasma cell malignancy with a significant heritable basis. Genome-wide association studies have transformed our understanding of MM predisposition, but individual studies have had limited power to discover risk loci. Here we perform a meta-analysis of these GWAS, add a new GWAS and perform replication analyses resulting in 9,866 cases and 239,188 controls. We confirm all nine known risk loci and discover eight new loci at 6p22.3 (rs34229995, P = 1.31 x 10(-8)), 6q21 (rs9372120, P = 9.09 x 10(-15)), 7q36.1 (rs7781265, P = 9.71 x 10(-9)), 8q24.21 (rs1948915, P = 4.20 x 10(-11)), 9p21.3 (rs2811710, P = 1.72 x 10(-13)), 10p12.1 (rs2790457, P = 1.77 x 10(-8)), 16q23.1 (rs7193541, P = 5.00 x 10(-12)) and 20q13.13 (rs6066835, P = 1.36 x 10(-13)), which localize in or near to JARID2, ATG5, SMARCD3, CCAT1, CDKN2A, WAC, RFWD3 and PREX1. These findings provide additional support for a polygenic model of MM and insight into the biological basis of tumour development.
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| 459. |
- Nowak, Grzegorz, et al.
(författare)
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K2-280 b - a low density warm sub-Saturn around a mildly evolved star
- 2020
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Ingår i: Monthly Notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 497:4, s. 4423-4435
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Tidskriftsartikel (refereegranskat)abstract
- We present an independent discovery and detailed characterization of K2-280 b, a transiting low density warm sub-Saturn in a 19.9-d moderately eccentric orbit (e = 0.35(-0.04)(+0.05)) from K2 campaign 7. A joint analysis of high precision HARPS, HARPS-N, and FIES radial velocity measurements and K2 photometric data indicates that K2-280 b has a radius of R-b = 7.50 +/- 0.44 R-circle plus and a mass of M-b = 37.1 +/- 5.6 M-circle plus, yielding a mean density of rho(b) = 0.48(-0.10)(+0.13) g cm(-3). The host star is a mildly evolved G7 star with an effective temperature of T-eff = 5500 +/- 100 K, a surface gravity of log g(star) = 4.21 +/- 0.05 (cgs), and an iron abundance of [Fe/H] = 0.33 +/- 0.08 dex, and with an inferred mass of M-star = 1.03 +/- 0.03 M-circle dot and a radius of R-star = 1.28 +/- 0.07 R-circle dot. We discuss the importance of K2-280 b for testing formation scenarios of sub-Saturn planets and the current sample of this intriguing group of planets that are absent in the Solar system.
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| 460. |
- Ohlin, C. Andre, et al.
(författare)
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Rates of Water Exchange for Two Cobalt(II) Heteropolyoxotungstate Compounds in Aqueous Solution
- 2011
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Ingår i: Chemistry - A European Journal. - : Wiley. - 0947-6539 .- 1521-3765. ; 17:16, s. 4408-4417
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Tidskriftsartikel (refereegranskat)abstract
- Polyoxometalate ions are used as ligands in water-oxidation processes related to solar energy production. An important step in these reactions is the association and dissociation of water from the catalytic sites, the rates of which are unknown. Here we report the exchange rates of water ligated to Co-II atoms in two polyoxotungstate sandwich molecules using the O-17-NMR-based Swift-Connick method. The compounds were the [Co-4(H2O)(2)(B-alpha-PW9O34)(2)](10-) and the larger alpha beta beta alpha-[Co-4(H2O)(2)(P2W15O56)(2)](16-) ions, each with two water molecules bound trans to one another in a Co-II sandwich between the tungstate ligands. The clusters, in both solid and solution state, were characterized by a range of methods, including NMR, EPR, FT-IR, UV-Vis, and EXAFS spectroscopy, ESI-MS, single-crystal Xray crystallography, and potentiometry. For [Co-4(H2O)(2)(B-alpha-PW9O34)(2)](10-) at pH 5.4, we estimate: k(298) = 1.5(5) +/- 0.3 x 10(6) s(-1), Delta H-not equal = 39.8 +/- 0.4 kJ mol(-1), Delta S-not equal = + 7.1 +/- 1.2 J mol(-1)K(-1) and Delta V-not equal = 5.6 +/- 1.6 cm(3)mol(-1). For the Wells-Dawson sandwich cluster (alpha beta beta alpha-[Co-4(H2O)(2)(P2W15O56)(2)](16-)) at pH 5.54, we find: k(298) = 1.6(2) +/- 0.3 x 10(6)s(-1), Delta H-not equal = 27.6 +/- 0.4 kJ mol(-1) Delta S-not equal = -33 +/- 1.3 J mol(-1)K(-1) and Delta V-not equal = 2.2 +/- 1.4 cm(3)mol(-1) at pH 5.2. The molecules are clearly stable and monospecific in slightly acidic solutions, but dissociate in strongly acidic solutions. This dissociation is detectable by EPR spectroscopy as S=3/2 Co-II species (such as the [Co(H2O)(6)](2+) monomer ion) and by the significant reduction of the Co-Co vector in the XAS spectra.
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