Does metformin improve vascular health in children with Type 1 diabetes? Protocol for a one year, double blind, randomised, placebo controlled trial

Background: Cardiovascular disease is the leading cause of mortality in Type 1 diabetes (T1D). Vascular dysfunction is an early and critical event in the development of cardiovascular disease. Children with T1D have vascular dysfunction therefore early interventions to improve vascular health are essential to reduce cardiovascular mortality in T1D. Metformin is an insulin sensitising agent which is known to improve vascular health outcomes in type 2 diabetes (T2D) and other individuals with insulin resistance. It has been used safely in children and adolescents with T2D for over 10 years. This study aims to assess the effect of metformin on vascular health in children with T1D. Methods/Design: This study is a 12 month, double blind, randomised, placebo controlled trial to determine the effect of metformin on vascular health in children (age 8–18) with T1D. The sample size is 76 with 38 children in the metformin group and 38 children in the placebo group. Vascular health and biochemical markers will be measured at baseline, 3, 6 and 12 months. Vascular function will be measured using flow mediated dilatation and glyceryl trinitrate mediated dilatation of the brachial artery and vascular structure will be measured with carotid and aortic intima media thickness, using standardised protocols. Discussion: This study will be the first to investigate the effect of metformin on vascular health in children with T1D. It will provide important information on a potential intervention to improve cardiovascular morbidity and mortality in this population at high risk from cardiovascular disease.Jemma Anderson, Alexia S Peña, Thomas Sullivan, Roger Gent, Bronwen D’Arcy, Timothy Olds, Brian Coppin and Jennifer Coupe

ALMA reveals a chemically evolved submillimeter galaxy at z=4.76

The chemical properties of high-z galaxies provide important information to constrain galaxy evolutionary scenarios. However, widely-used metallicity diagnostics based on rest-frame optical emission lines are not usable for heavily dust-enshrouded galaxies (such as Sub-Millimeter Galaxies; SMGs), especially at z>3. Here we focus on the flux ratio of the far-infrared fine-structure emission lines [NII]205um and [CII]158um to assess the metallicity of high-z SMGs. Through ALMA cycle 0 observations, we have detected the [NII]205um emission in a strongly [CII]-emitting SMG, LESS J033229.4-275619 at z=4.76. The velocity-integrated [NII]/[CII] flux ratio is 0.043 +/- 0.008. This is the first measurement of the [NII]/[CII] flux ratio in high-z galaxies, and the inferred flux ratio is similar to the ratio observed in the nearby universe (~0.02-0.07). The velocity-integrated flux ratio and photoionization models suggest that the metallicity in this SMG is consistent with solar, implying the chemical evolution has progressed very rapidly in this system at z=4.76. We also obtain a tight upper limit on the CO(12-11) transition, which translates into CO(12-11)/CO(2-1) <3.8 (3 sigma). This suggests that the molecular gas clouds in LESS J033229.4-275619 are not affected significantly by the radiation field emitted by the AGN in this system.Comment: 5 pages, 3 figures, accepted for publication in Astronomy and Astrophysics Letter

AzTEC Millimetre Survey of the COSMOS Field - II. Source Count Overdensity and Correlations with Large-Scale Structure

We report an over-density of bright sub-millimetre galaxies (SMGs) in the 0.15 sq. deg. AzTEC/COSMOS survey and a spatial correlation between the SMGs and the optical-IR galaxy density at z <~ 1.1. This portion of the COSMOS field shows a ~ 3-sigma over-density of robust SMG detections when compared to a background, or "blankfield", population model that is consistent with SMG surveys of fields with no extragalactic bias. The SMG over-density is most significant in the number of very bright detections (14 sources with measured fluxes S(1.1mm) > 6 mJy), which is entirely incompatible with sample variance within our adopted blank-field number densities and infers an over-density significance of >> 4. We find that the over-density and spatial correlation to optical-IR galaxy density are most consistent with lensing of a background SMG population by foreground mass structures along the line of sight, rather than physical association of the SMGs with the z <~ 1.1 galaxies/clusters. The SMG positions are only weakly correlated with weak-lensing maps, suggesting that the dominant sources of correlation are individual galaxies and the more tenuous structures in the region and not the massive and compact clusters. These results highlight the important roles cosmic variance and large-scale structure can play in the study of SMGs.Comment: 12 pages, 11 figures, 2 tables, accepted for publication in MNRA

The faint counterparts of MAMBO mm sources near the NTT Deep Field

We discuss identifications for 18 sources from our MAMBO 1.2mm survey of the region surrounding the NTT Deep Field. We have obtained accurate positions from Very Large Array 1.4GHz interferometry and in a few cases IRAM mm interferometry, and have also made deep BVRIzJK imaging at ESO. We find thirteen 1.2mm sources associated with optical/near-infrared objects in the magnitude range K=19.0 to 22.5, while five are blank fields at K>22. The median redshift of the radio-identified mm sources is ~2.6 from the radio/mm estimator, and the median optical/near-infrared photometric redshifts for the objects with counterparts ~2.1. This suggests that those radio-identified mm sources without optical/near-infrared counterparts tend to lie at higher redshifts than those with optical/near-infrared counterparts. Compared to published identifications of objects from 850micron surveys of similar depth, the median K and I magnitudes of our counterparts are roughly two magnitudes fainter and the dispersion of I-K colors is less. Real differences in the median redshifts, residual mis-identifications with bright objects, cosmic variance, and small number statistics are likely to contribute to this significant difference, which also affects redshift measurement strategies. We discuss basic properties of the near-infrared/(sub)mm/radio spectral energy distributions of our galaxies and of interferometrically identified submm sources from the literature. From a comparison with submm objects with CO-confirmed spectroscopic redshifts we argue that roughly two thirds of the (sub)mm galaxies are at z>~2.5. This fraction is probably larger when including sources without radio counterparts. (abridged)Comment: 45 pages, 9 figures. Accepted by ApJ. The resolution of figures 2 and 3 has been degraded. A higher quality pdf version of this paper is available at http://www.mpe.mpg.de/~dannerb

Deep 1.1 mm-wavelength imaging of the GOODS-S field by AzTEC/ASTE - I. Source catalogue and number counts

[Abridged] We present the first results from a 1.1 mm confusion-limited map of the GOODS-S field taken with AzTEC on the ASTE telescope. We imaged a 270 sq. arcmin field to a 1\sigma depth of 0.48 - 0.73 mJy/beam, making this one of the deepest blank-field surveys at mm-wavelengths ever achieved. Although our GOODS-S map is extremely confused, we demonstrate that our source identification and number counts analyses are robust, and the techniques discussed in this paper are relevant for other deeply confused surveys. We find a total of 41 dusty starburst galaxies with S/N >= 3.5 within this uniformly covered region, where only two are expected to be false detections. We derive the 1.1mm number counts from this field using both a "P(d)" analysis and a semi-Bayesian technique, and find that both methods give consistent results. Our data are well-fit by a Schechter function model with (S', N(3mJy), \alpha) = (1.30+0.19 mJy, 160+27 (mJy/deg^2)^(-1), -2.0). Given the depth of this survey, we put the first tight constraints on the 1.1 mm number counts at S(1.1mm) = 0.5 mJy, and we find evidence that the faint-end of the number counts at S(850\mu m) < 2.0 mJy from various SCUBA surveys towards lensing clusters are biased high. In contrast to the 870 \mu m survey of this field with the LABOCA camera, we find no apparent under-density of sources compared to previous surveys at 1.1 mm. Additionally, we find a significant number of SMGs not identified in the LABOCA catalogue. We find that in contrast to observations at wavelengths < 500 \mu m, MIPS 24 \mu m sources do not resolve the total energy density in the cosmic infrared background at 1.1 mm, demonstrating that a population of z > 3 dust-obscured galaxies that are unaccounted for at these shorter wavelengths potentially contribute to a large fraction (~2/3) of the infrared background at 1.1 mm.Comment: 21 pages, 9 figures. Accepted to MNRAS

A Simple Kinetic Model Describes the Processivity of Myosin-V

Myosin-V is a motor protein responsible for organelle and vesicle transport in cells. Recent single-molecule experiments have shown that it is an efficient processive motor that walks along actin filaments taking steps of mean size close to 36 nm. A theoretical study of myosin-V motility is presented following an approach used successfully to analyze the dynamics of conventional kinesin but also taking some account of step-size variations. Much of the present experimental data for myosin-V can be well described by a two-state chemical kinetic model with three load-dependent rates. In addition, the analysis predicts the variation of the mean velocity and of the randomness -- a quantitative measure of the stochastic deviations from uniform, constant-speed motion -- with ATP concentration under both resisting and assisting loads, and indicates a {\it sub}step of size $d_{0} \simeq$ 13-14 nm (from the ATP-binding site) that appears to accord with independent observations.Comment: 20 pages, 7 figures, to be published in Biophys. J. in 200

AzTEC millimeter survey of the COSMOS field - III. Source catalog over 0.72 sq. deg. and plausible boosting by large-scale structure

We present a 0.72 sq. deg. contiguous 1.1mm survey in the central area of the COSMOS field carried out to a 1sigma ~ 1.26 mJy/beam depth with the AzTEC camera mounted on the 10m Atacama Submillimeter Telescope Experiment (ASTE). We have uncovered 189 candidate sources at a signal-to-noise ratio S/N >= 3.5, out of which 129, with S/N >= 4, can be considered to have little chance of being spurious (< 2 per cent). We present the number counts derived with this survey, which show a significant excess of sources when compared to the number counts derived from the ~0.5 sq. deg. area sampled at similar depths in the Scuba HAlf Degree Extragalactic Survey (SHADES, Austermann et al. 2010). They are, however, consistent with those derived from fields that were considered too small to characterize the overall blank-field population. We identify differences to be more significant in the S > 5 mJy regime, and demonstrate that these excesses in number counts are related to the areas where galaxies at redshifts z < 1.1 are more densely clustered. The positions of optical-IR galaxies in the redshift interval 0.6 < z < 0.75 are the ones that show the strongest correlation with the positions of the 1.1mm bright population (S > 5 mJy), a result which does not depend exclusively on the presence of rich clusters within the survey sampled area. The most likely explanation for the observed excess in number counts at 1.1mm is galaxy-galaxy and galaxy-group lensing at moderate amplification levels, that increases in amplitude as one samples larger and larger flux densities. This effect should also be detectable in other high redshift populations.Comment: 21 pages, 17 figures, accepted for publication in MNRA

Star Formation from Galaxies to Globules

The empirical laws of star formation suggest that galactic-scale gravity is involved, but they do not identify the actual triggering mechanisms for clusters in the final stages. Many other triggering processes satisfy the empirical laws too, including turbulence compression and expanding shell collapse. The self-similar nature of the gas and associated young stars suggests that turbulence is more directly involved, but the small scale morphology of gas around most embedded clusters does not look like a random turbulent flow. Most clusters look triggered by other nearby stars. Such a prominent local influence makes it difficult to understand the universality of the Kennicutt and Schmidt laws on galactic scales. A unified view of multi-scale star formation avoids most of these problems. Ambient self-gravity produces spiral arms and drives much of the turbulence that leads to self-similar structures, while localized energy input from existing clusters and field supernovae triggers new clusters in pre-existing clouds. The hierarchical structure in the gas made by turbulence ensures that the triggering time scales with size, giving the Schmidt law over a wide range of scales and the size-duration correlation for young star fields. The efficiency of star formation is determined by the fraction of the gas above a critical density of around 10^5 m(H2)/cc. Star formation is saturated to its largest possible value given the fractal nature of the interstellar medium.Comment: accepted for ApJ, 42 pages, Dannie Heineman prize lecture, January 200