Measurement of liver iron by magnetic resonance imaging in the UK Biobank population

The burden of liver disease continues to increase in the UK, with liver cirrhosis reported to be the third most common cause of premature death. Iron overload, a condition that impacts liver health, was traditionally associated with genetic disorders such as hereditary haemochromatosis, however, it is now increasingly associated with obesity, type-2 diabetes and non-alcoholic fatty liver disease. The aim of this study was to assess the prevalence of elevated levels of liver iron within the UK Biobank imaging study in a cohort of 9108 individuals. Magnetic resonance imaging (MRI) was undertaken at the UK Biobank imaging centre, acquiring a multi-echo spoiled gradient-echo single-breath-hold MRI sequence from the liver. All images were analysed for liver iron and fat (expressed as proton density fat fraction or PDFF) content using LiverMultiScan™. Liver iron was measured in 97.3% of the cohort. The mean liver iron content was 1.32 ± 0.32 mg/g while the median was 1.25 mg/g (min: 0.85 max: 6.44 mg/g). Overall 4.82% of the population were defined as having elevated liver iron, above commonly accepted 1.8 mg/g threshold based on biochemical iron measurements in liver specimens obtained by biopsy. Further analysis using univariate models showed elevated liver iron to be related to male sex (p5.6% PDFF) was associated with a slight increase in prevalence of elevated liver iron (4.4% vs 6.3%, p=0.0007). This study shows that population studies including measurement of liver iron concentration are feasible, which may in future be used to better inform patient stratification and treatment

Using Co-solvability to Model and Exploit Synergetic Effects in Evolution

We introduce, analyze, and experimentally verify the concept of co-solvability, meant as the ability of a solution maintained by an evolutionary run to solve (correctly process) a pair of fitness cases (tests). The method based on this concept can be considered as a second-order implicit fitness sharing, where solutions compete for the rewards granted for solving pairs of tests, rather than single tests. We prove that co-solvability fitness function is by definition synergistic and imposes selection pressure which is qualitatively different from that induced by standard fitness function or implicit fitness sharing. The results of experimental verification on eight genetic programming tasks demonstrate that evolutionary runs driven by the proposed fitness function usually converge faster to global optima than other methods

Low thrust propulsion in a coplanar circular restricted four body problem

This paper formulates a circular restricted four body problem (CRFBP), where the three primaries are set in the stable Lagrangian equilateral triangle configuration and the fourth body is massless. The analysis of this autonomous coplanar CRFBP is undertaken, which identies eight natural equilibria; four of which are close to the smaller body, two stable and two unstable, when considering the primaries to be the Sun and two smaller bodies of the solar system. Following this, the model incorporates `near term' low-thrust propulsion capabilities to generate surfaces of articial equilibrium points close to the smaller primary, both in and out of the plane containing the celestial bodies. A stability analysis of these points is carried out and a stable subset of them is identied. Throughout the analysis the Sun-Jupiter-Asteroid-Spacecraft system is used, for conceivable masses of a hypothetical asteroid set at the libration point L4. It is shown that eight bounded orbits exist, which can be maintained with a constant thrust less than 1:5 10􀀀4N for a 1000kg spacecraft. This illustrates that, by exploiting low-thrust technologies, it would be possible to maintain an observation point more than 66% closer to the asteroid than that of a stable natural equilibrium point. The analysis then focusses on a major Jupiter Trojan: the 624-Hektor asteroid. The thrust required to enable close asteroid observation is determined in the simplied CRFBP model. Finally, a numerical simulation of the real Sun-Jupiter-624 Hektor-Spacecraft is undertaken, which tests the validity of the stability analysis of the simplied model

Scientific Preparations for Lunar Exploration with the European Lunar Lander

This paper discusses the scientific objectives for the ESA Lunar Lander Mission, which emphasise human exploration preparatory science and introduces the model scientific payload considered as part of the on-going mission studies, in advance of a formal instrument selection.Comment: Accepted for Publication in Planetary and Space Science 51 pages, 8 figures, 1 tabl

Algebraic Solution of the Supersymmetric Hydrogen Atom in d Dimensions

In this paper the N=2 supersymmetric extension of the Schroedinger Hamiltonian with 1/r-potential in arbitrary space-dimensions is constructed. The supersymmetric hydrogen atom admits a conserved Laplace-Runge-Lenz vector which extends the rotational symmetry SO(d) to a hidden SO(d+1) symmetry. This symmetry of the system is used to determine the discrete eigenvalues with their degeneracies and the corresponding bound state wave functions.Comment: 36 pages, 6 figure

An approximate renormalization-group transformation for Hamiltonian systems with three degrees of freedom

We construct an approximate renormalization transformation that combines Kolmogorov-Arnold-Moser (KAM)and renormalization-group techniques, to analyze instabilities in Hamiltonian systems with three degrees of freedom. This scheme is implemented both for isoenergetically nondegenerate and for degenerate Hamiltonians. For the spiral mean frequency vector, we find numerically that the iterations of the transformation on nondegenerate Hamiltonians tend to degenerate ones on the critical surface. As a consequence, isoenergetically degenerate and nondegenerate Hamiltonians belong to the same universality class, and thus the corresponding critical invariant tori have the same type of scaling properties. We numerically investigate the structure of the attracting set on the critical surface and find that it is a strange nonchaotic attractor. We compute exponents that characterize its universality class.Comment: 10 pages typeset using REVTeX, 7 PS figure

Toward a Global Space Exploration Program: A Stepping Stone Approach

Sovereignty, International Governance and Global Value

FGF receptor genes and breast cancer susceptibility: results from the Breast Cancer Association Consortium

Background:Breast cancer is one of the most common malignancies in women. Genome-wide association studies have identified FGFR2 as a breast cancer susceptibility gene. Common variation in other fibroblast growth factor (FGF) receptors might also modify risk. We tested this hypothesis by studying genotyped single-nucleotide polymorphisms (SNPs) and imputed SNPs in FGFR1, FGFR3, FGFR4 and FGFRL1 in the Breast Cancer Association Consortium. Methods:Data were combined from 49 studies, including 53 835 cases and 50 156 controls, of which 89 050 (46 450 cases and 42 600 controls) were of European ancestry, 12 893 (6269 cases and 6624 controls) of Asian and 2048 (1116 cases and 932 controls) of African ancestry. Associations with risk of breast cancer, overall and by disease sub-type, were assessed using unconditional logistic regression. Results:Little evidence of association with breast cancer risk was observed for SNPs in the FGF receptor genes. The strongest evidence in European women was for rs743682 in FGFR3; the estimated per-allele odds ratio was 1.05 (95 confidence interval=1.02-1.09, P=0.0020), which is substantially lower than that observed for SNPs in FGFR2. Conclusion:Our results suggest that common variants in the other FGF receptors are not associated with risk of breast cancer to the degree observed for FGFR2. © 2014 Cancer Research UK