Polygenic transcriptome risk scores (PTRS) can improve portability of polygenic risk scores across ancestries

Background: Polygenic risk scores (PRS) are valuable to translate the results of genome-wide association studies (GWAS) into clinical practice. To date, most GWAS have been based on individuals of European-ancestry leading to poor performance in populations of non-European ancestry. Results: We introduce the polygenic transcriptome risk score (PTRS), which is based on predicted transcript levels (rather than SNPs), and explore the portability of PTRS across populations using UK Biobank data. Conclusions: We show that PTRS has a significantly higher portability (Wilcoxon p=0.013) in the African-descent samples where the loss of performance is most acute with better performance than PRS when used in combination

The nature of the SDSS galaxies in various classes based on morphology, colour and spectral features -- I. Optical properties

We present a comprehensive study of the nature of the SDSS galaxies divided into various classes based on their morphology, colour, and spectral features. The SDSS galaxies are classified into early-type and late-type; red and blue; passive, HII, Seyfert, and LINER, returning a total of 16 fine classes of galaxies. We examine the luminosity dependence of seven physical parameters of galaxies in each class. We find that more than half of red early-type galaxies (REGs) have star formation or AGN activity, and that these active REGs have smaller axis ratio and bluer outside compared to the passive REGs. Blue early-type galaxies (BEGs) show structural features similar to those of REGs, but their centres are bluer than REGs. HII BEGs are found to have bluer centres than passive BEGs, but HII REGs have bluer outside than passive REGs. Bulge-dominated late-type galaxies have red colours. Passive red late-types are similar to REGs in several aspects. Most blue late-type galaxies (BLGs) have forming stars, but a small fraction of BLGs do not show evidence for current star formation activity. Differences of other physical parameters among different classes are inspected, and their implication on galaxy evolution is discussed.Comment: 16 pages, 10 tables, 16 figures; accepted for publication in MNRA

Epigenetic regulation of cyclooxygenase-2 by methylation of c8orf4 in pulmonary fibrosis

Fibroblasts derived from the lungs of patients with idiopathic pulmonary fibrosis (IPF) and systemic sclerosis (SSc) produce low levels of prostaglandin (PG) E(2), due to a limited capacity to up-regulate cyclooxygenase-2 (COX-2). This deficiency contributes functionally to the fibroproliferative state, however the mechanisms responsible are incompletely understood. In the present study, we examined whether the reduced level of COX-2 mRNA expression observed in fibrotic lung fibroblasts is regulated epigenetically. The DNA methylation inhibitor, 5-aza-2′-deoxycytidine (5AZA) restored COX-2 mRNA expression by fibrotic lung fibroblasts dose dependently. Functionally, this resulted in normalization of fibroblast phenotype in terms of PGE(2) production, collagen mRNA expression and sensitivity to apoptosis. COX-2 methylation assessed by bisulfite sequencing and methylation microarrays was not different in fibrotic fibroblasts compared with controls. However, further analysis of the methylation array data identified a transcriptional regulator, chromosome 8 open reading frame 4 (thyroid cancer protein 1, TC-1) (c8orf4), which is hypermethylated and down-regulated in fibrotic fibroblasts compared with controls. siRNA knockdown of c8orf4 in control fibroblasts down-regulated COX-2 and PGE(2) production generating a phenotype similar to that observed in fibrotic lung fibroblasts. Chromatin immunoprecipitation demonstrated that c8orf4 regulates COX-2 expression in lung fibroblasts through binding of the proximal promoter. We conclude that the decreased capacity of fibrotic lung fibroblasts to up-regulate COX-2 expression and COX-2-derived PGE(2) synthesis is due to an indirect epigenetic mechanism involving hypermethylation of the transcriptional regulator, c8orf4

A pilot telephone intervention to increase uptake of breast cancer screening in socially deprived areas in Scotland (TELBRECS):study protocol for a randomised controlled trial

BACKGROUND Breast cancer accounts for almost 30% of all cancers and is the second leading cause of cancer deaths in women in Scotland. Screening is key to early detection. The Scottish Breast Screening Programme is a nationwide, free at point of delivery screening service, to which all women aged between 50 and 70 years are invited to attend every 3 years. Currently over three-quarters of invited women regularly attend screening. However, women from more deprived areas are much less likely to attend: for example in the 3 years from 2010-2012 only 63% of women in the most deprived area attended the East of Scotland Breast Screening programme versus 81% in the least deprived. Research has suggested that reminders (telephone or letter) and brief, personalised interventions addressing barriers to attendance may be helpful in increasing uptake in low-income women. METHODS/DESIGN We will employ a brief telephone reminder and support intervention, whose purpose is to elicit and address any mistaken beliefs women have about breast screening, with the aim that the perceived benefits of screening come to outweigh any perceived barriers for individuals. We will test whether this intervention, plus a simple anticipated regret manipulation, will lead to an increase in the uptake of breast cancer screening amongst low-income women who have failed to attend a first appointment, in a randomised controlled trial with 600 women. Participants will be randomly allocated to one of four treatment arms i.e. 1) Letter reminder (i.e. Treatment as usual: CONTROL); 2) Telephone reminder (TEL), 3) Telephone reminder plus telephone support (TEL-SUPP) and 4) Telephone reminder plus support plus AR (TEL-SUPP-AR). The primary outcome will be attendance at breast screening within 3 months of the reminder letter. DISCUSSION If this simple telephone support intervention (with or without AR intervention) leads to a significant increase in breast screening attendance, this would represent a rare example of a theoretically-driven, relatively simple psychological intervention that could result in earlier detection of breast cancer amongst an under-served group of lower socio-economic women. TRIAL REGISTRATION Current Controlled trials: ISRCTN06039270. Registered 16th January 2014

Evolution in the Disks and Bulges of Group Galaxies since z=0.4

We present quantitative morphology measurements of a sample of optically selected group galaxies at 0.3 < z < 0.55 using the Hubble Space Telescope (HST) Advanced Camera for Surveys (ACS) and the GIM2D surface brightness--fitting software package. The group sample is derived from the Canadian Network for Observational Cosmology Field Redshift survey (CNOC2) and follow-up Magellan spectroscopy. We compare these measurements to a similarly selected group sample from the Millennium Galaxy Catalogue (MGC) at 0.05 < z < 0.12. We find that, at both epochs, the group and field fractional bulge luminosity (B/T) distributions differ significantly, with the dominant difference being a deficit of disk--dominated (B/T < 0.2) galaxies in the group samples. At fixed luminosity, z=0.4 groups have ~ 5.5 +/- 2 % fewer disk--dominated galaxies than the field, while by z=0.1 this difference has increased to ~ 19 +/- 6 %. Despite the morphological evolution we see no evidence that the group environment is actively perturbing or otherwise affecting the entire existing disk population. At both redshifts, the disks of group galaxies have similar scaling relations and show similar median asymmetries as the disks of field galaxies. We do find evidence that the fraction of highly asymmetric, bulge--dominated galaxies is 6 +/- 3 % higher in groups than in the field, suggesting there may be enhanced merging in group environments. We replicate our group samples at z=0.4 and z=0 using the semi-analytic galaxy catalogues of Bower et al (2006). This model accurately reproduces the B/T distributions of the group and field at z=0.1. However, the model does not reproduce our finding that the deficit of disks in groups has increased significantly since z=0.4.Comment: Accepted for publication in MNRAS. 20 pages, 17 figure

Hubble Space Telescope Imaging of the CFRS and LDSS Redshift Surveys---III. Field elliptical galaxies at 0.2 < z < 1.0

Surface photometry has been performed on a sample of 46 field elliptical galaxies. These galaxies are described well by a deVaucouleurs R^{1/4} profile. The sample was selected from the combined Canada-France and LDSS redshift surveys and spans the range 0.20 < z < 1.00. The relationship between galaxy half-light radius and luminosity evolves such that a galaxy of a given size is more luminous by Delta M_B=-0.97 \pm 0.14 mag at z=0.92 and the mean rest-frame color shifts blueward by Delta (U-V) =-0.68 \pm 0.11 at z=0.92 relative to the local cluster relations. Approximately 1/3 of these elliptical galaxies exhibit [OII] 3727 emission lines with equivalent widths > 15 angstroms indicating ongoing star formation. Estimated star-formation rates imply that \le 5% of the stellar mass in the elliptical galaxy population has been formed since z=1. We see no evidence for a decline in the space density of early-type galaxies with look-back time. The statistics and a comparison with local luminosity functions are both consistent with the view that the population of massive early-type galaxies was largely in place by z~1. This implies that merging is not required since that time to produce the present-day space density of elliptical galaxies.Comment: 21 pages plus 8 figures plus 5 tables. Accepted by Astrophysical Journa

Network model of immune responses reveals key effectors to single and co-infection dynamics by a respiratory bacterium and a gastrointestinal helminth

Co-infections alter the host immune response but how the systemic and local processes at the site of infection interact is still unclear. The majority of studies on co-infections concentrate on one of the infecting species, an immune function or group of cells and often focus on the initial phase of the infection. Here, we used a combination of experiments and mathematical modelling to investigate the network of immune responses against single and co-infections with the respiratory bacterium Bordetella bronchiseptica and the gastrointestinal helminth Trichostrongylus retortaeformis. Our goal was to identify representative mediators and functions that could capture the essence of the host immune response as a whole, and to assess how their relative contribution dynamically changed over time and between single and co-infected individuals. Network-based discrete dynamic models of single infections were built using current knowledge of bacterial and helminth immunology; the two single infection models were combined into a co-infection model that was then verified by our empirical findings. Simulations showed that a T helper cell mediated antibody and neutrophil response led to phagocytosis and clearance of B. bronchiseptica from the lungs. This was consistent in single and co-infection with no significant delay induced by the helminth. In contrast, T. retortaeformis intensity decreased faster when co-infected with the bacterium. Simulations suggested that the robust recruitment of neutrophils in the co-infection, added to the activation of IgG and eosinophil driven reduction of larvae, which also played an important role in single infection, contributed to this fast clearance. Perturbation analysis of the models, through the knockout of individual nodes (immune cells), identified the cells critical to parasite persistence and clearance both in single and co-infections. Our integrated approach captured the within-host immuno-dynamics of bacteria-helminth infection and identified key components that can be crucial for explaining individual variability between single and co-infections in natural populations

Complex-Distance Potential Theory and Hyperbolic Equations

An extension of potential theory in R^n is obtained by continuing the Euclidean distance function holomorphically to C^n. The resulting Newtonian potential is generated by an extended source distribution D(z) in C^n whose restriction to R^n is the delta function. This provides a natural model for extended particles in physics. In C^n, interpreted as complex spacetime, D(z) acts as a propagator generating solutions of the wave equation from their initial values. This gives a new connection between elliptic and hyperbolic equations that does not assume analyticity of the Cauchy data. Generalized to Clifford analysis, it induces a similar connection between solutions of elliptic and hyperbolic Dirac equations. There is a natural application to the time-dependent, inhomogeneous Dirac and Maxwell equations, and the `electromagnetic wavelets' introduced previously are an example.Comment: 25 pages, submited to Proceedings of 5th Intern. Conf. on Clifford Algebras, Ixtapa, June 24 - July 4, 199

The morphologies and masses of extremely red galaxies in the Groth Strip survey

We present a new cataloge of EROs from the Groth strip and study the relation between their morphology and mass. We find 102 EROs (F814W-K=>4, K<=21.0), over a survey area of 155 arcmin^2. The photometric data include U,B,F606W,F814W,J,K bands. Morphologies are based on a by eye classification and we distinguish between 3 basic classes: compact objects, targets with a disc and/or a bulge component and irregular or merger candidates. The majority of our targets has either a very compact morphology (33+-6%), or show more or less distinct disc components (41+-6%). 14+-4% are merger or irregulars and 7 objects could not be classified. We also study the dependence of structural parameters on morphological appearance. EROs that are either compact or show a distinct bulge component have smaller median effective radii (1.22+-0.14 kpc and 3.31+-0.53 kpc) than disc dominated (5.50+-0.51 kpc) or possible irregular galaxies or merger candidates (4.92+-0.14 kpc). The Sersic index changes from 2.30+-0.34 and 3.24+-0.55, to 1.03+-0.24 and 1.54+-0.40 respectively. Most the EROs in our sample have redshifts between z=1 and z=2; however, compact EROs in our sample are found at redshifts as low as z=0.4 and as high as z=2.8; the latter qualify as well as DRGs. Disc-like EROs are also found up to z=2.8; however those with a bulge-disc structure are only seen at z<1.5. For each of these EROs we determined the stellar mass and mean population age by fitting synthetic Bruzual (2007) spectra to the SED. Mass estimates were obtained by assuming an exponentially declining star formation rate. Total stellar masses are in the range 9.1<log(M/M_sun)<11.6. We cannot detect significant differences between the stellar mass distribution of the morphological classes. EROs with masses of log(M/M_sun)>11.0 dominantly show compact morphologies, but also include a significant number of sources with a disc morphology.Comment: 21 pages, 17 figures, accepted for publication in MNRA

Automated Morphological Classification of SDSS Red Sequence Galaxies

(abridged) In the last decade, the advent of enormous galaxy surveys has motivated the development of automated morphological classification schemes to deal with large data volumes. Existing automated schemes can successfully distinguish between early and late type galaxies and identify merger candidates, but are inadequate for studying detailed morphologies of red sequence galaxies. To fill this need, we present a new automated classification scheme that focuses on making finer distinctions between early types roughly corresponding to Hubble types E, S0, and Sa. We visually classify a sample of 984 non-starforming SDSS galaxies with apparent sizes >14". We then develop an automated method to closely reproduce the visual classifications, which both provides a check on the visual results and makes it possible to extend morphological analysis to much larger samples. We visually classify the galaxies into three bulge classes (BC) by the shape of the light profile in the outer regions: discs have sharp edges and bulges do not, while some galaxies are intermediate. We separately identify galaxies with features: spiral arms, bars, clumps, rings, and dust. We find general agreement between BC and the bulge fraction B/T measured by the galaxy modeling package GIM2D, but many visual discs have B/T>0.5. Three additional automated parameters -- smoothness, axis ratio, and concentration -- can identify many of these high-B/T discs to yield automated classifications that agree ~70% with the visual classifications (>90% within one BC). Both methods are used to study the bulge vs. disc frequency as a function of four measures of galaxy 'size': luminosity, stellar mass, velocity dispersion, and radius. All size indicators show a fall in disc fraction and a rise in bulge fraction among larger galaxies.Comment: 24 pages, 20 figures, MNRAS accepte