Multicentric validation of proteomic biomarkers in urine specific for diabetic nephropathy

Background: Urine proteome analysis is rapidly emerging as a tool for diagnosis and prognosis in disease states. For diagnosis of diabetic nephropathy (DN), urinary proteome analysis was successfully applied in a pilot study. The validity of the previously established proteomic biomarkers with respect to the diagnostic and prognostic potential was assessed on a separate set of patients recruited at three different European centers. In this case-control study of 148 Caucasian patients with diabetes mellitus type 2 and duration >= 5 years, cases of DN were defined as albuminuria >300 mg/d and diabetic retinopathy (n = 66). Controls were matched for gender and diabetes duration (n = 82). Methodology/Principal Findings: Proteome analysis was performed blinded using high-resolution capillary electrophoresis coupled with mass spectrometry (CE-MS). Data were evaluated employing the previously developed model for DN. Upon unblinding, the model for DN showed 93.8% sensitivity and 91.4% specificity, with an AUC of 0.948 (95% CI 0.898-0.978). Of 65 previously identified peptides, 60 were significantly different between cases and controls of this study. In <10% of cases and controls classification by proteome analysis not entirely resulted in the expected clinical outcome. Analysis of patient's subsequent clinical course revealed later progression to DN in some of the false positive classified DN control patients. Conclusions: These data provide the first independent confirmation that profiling of the urinary proteome by CE-MS can adequately identify subjects with DN, supporting the generalizability of this approach. The data further establish urinary collagen fragments as biomarkers for diabetes-induced renal damage that may serve as earlier and more specific biomarkers than the currently used urinary albumin

Assessment of fetal presentation: Exploring a woman-centred approach

This article explores the core midwifery skill of fetal presentation assessment from the perspective of women’s meanings and experiences, including the social and relational aspects of antenatal palpation. Brief background information is provided, explaining the clinical purpose of determining presentation antenatally, and the key debates surrounding the available interventions applied when babies present breech, eg. external cephalic version and caesarean section. In order to make the screening process transparent, women need to know the accuracy (or rather, inaccuracy) of abdominal palpation, and what her options will be if her baby is found to be presenting breech, either before or during labour. Specialist midwifery care may help meet women’s increased needs for counselling and reassurance, and provide continuity throughout the breech care pathway, which for low-risk women begins with palpation

The Average Optical Spectra of Intense Starbursts at z~2: Outflows and the Pressurization of the ISM

An important property of star-forming galaxies at z~1-2 is the high local star-formation intensities they maintain over tens of kiloparsecs at levels that are only observed in the nearby Universe in the most powerful nuclear starbursts. To investigate how these high star-formation intensities affect the warm ionized medium, we present an analysis of the average spectra of about 50 such galaxies at z~1.2-2.6 and of subsamples selected according to their local and global star-formation intensity. Stacking allows us to probe relatively weak lines like [SII]\lambda \lambda 6716,6731 and [OI]\lambda 6300, which are tracers of the conditions of the ISM and are undetectable in most individual targets. We find higher gas densities (hence pressures) in intensely star-forming regions compared to fainter diffuse gas and, overall, values that are comparable to starburst regions and the diffuse ISM in nearby galaxies. By modeling the H\alpha\ surface brightnesses and [SII]/H\alpha\ line ratios with the Cloudy photoionization code, we find that our galaxies continue trends observed in local galaxies, where gas pressures scale with star-formation intensity. We discuss these results in the context of models of self-regulated star formation, where star formation determines the average thermal and turbulent pressure in the ISM, which in turn determines the rate at which stars can form, finding good agreement with our data. We also confirm the detection of broad, faint lines underlying H\alpha\ and [NII], which have previously been considered evidence of either outflows or active galactic nuclei. Finding that the broad component is only significantly detected in stacks with the highest average local and global star-formation intensities strongly supports the outflow interpretation, and further emphasizes the importance of star-formation feedback and self-regulation in the early Universe.Comment: 7 pages, 4 figures, accepted for publication in Astronomy and Astrophysic

On the self-regulation of intense star-formation in galaxies at z=1-3

(abridged) We have analyzed the properties of the rest-frame optical emission lines of a sample of 53 intensely star forming galaxies at z=1.3 to 2.7 observed with SINFONI on the ESO-VLT. We find large velocity dispersions in the lines, sigma=30-250 km/s. Our data agree well with simulations where we applied beam-smearing and assumed a scaling relation of the form: velocity dispersion is proportional to the square root of the star-formation intensity (star-formation rate per unit area). We conclude that the dispersions are primarily driven by star formation. To explain the high surface brightness and optical line ratios, high thermal pressures in the warm ionized medium, WIM, are required (log P/k (K/cm^3)>~6-7). Such thermal pressures in the WIM are similar to those observed in nearby starburst galaxies, but occur over much larger physical scales. Moreover, the relatively low ionization parameters necessary to fit the high surface brightnesses and optical line ratios suggest that the gas is not only directly associated with regions of star formation, but is wide spread throughout the general ISM. Thus the optical emission line gas is a tracer of the large scale dynamics of the bulk of the ISM. We present a simple model for the energy input from young stars in an accreting galaxy, to argue that the intense star-formation is supporting high turbulent pressure, which roughly balances the gravitational pressure and thus enables distant gas accreting disks to maintain a Toomre disk instability parameter Q~1. For a star formation efficiency of 3%, only 5-15% of the mechanical energy from young stars that is deposited in the ISM is needed to support the level of turbulence required for maintaining this balance. Since this balance is maintained by energy injected into the ISM by the young stars themselves, this suggests that star formation in high redshift galaxies is self-regulating.Comment: A&A in press; 15 figure

Physical conditions in the ISM of intensely star-forming galaxies at redshift~2

We analyze the physical conditions in the interstellar gas of 11 actively star-forming galaxies at z~2, based on integral-field spectroscopy from the ESO-VLT and HST/NICMOS imaging. We concentrate on the high H-alpha surface brightnesses, large line widths, line ratios and the clumpy nature of these galaxies. We show that photoionization calculations and emission line diagnostics imply gas pressures and densities that are similar to the most intense nearby star-forming regions at z=0 but over much larger scales (10-20 kpc). A relationship between surface brightness and velocity dispersion can be explained through simple energy injection arguments and a scaling set by nearby galaxies with no free parameters. The high velocity dispersions are a natural consequence of intense star formation thus regions of high velocity dispersion are not evidence for mass concentrations such as bulges or rings. External mechanisms like cosmological gas accretion generally do not have enough energy to sustain the high velocity dispersions. In some cases, the high pressures and low gas metallicites may make it difficult to robustly distinguish between AGN ionization cones and star formation, as we show for BzK-15504 at z=2.38. We construct a picture where the early stages of galaxy evolution are driven by self-gravity which powers strong turbulence until the velocity dispersion is high. Then massive, dense, gas-rich clumps collapse, triggering star formation with high efficiencies and intensities as observed. At this stage, the intense star formation is likely self-regulated by the mechanical energy output of massive stars.Comment: ApJ accepted main journal, 21 pages, 12 figure

Can Cosmological Accretion be Observed in H-alpha at z~2?

In previous studies, it has been shown that the large line widths observed in high surface brightness H-alpha emitters at low and high redshifts are likely due to the mechanical energy injected by intense star formation. Here we discuss the possibility that the high surface brightnesses observed are not due to star formation, but due to cosmological gas accretion. We assume that all of the accretion energy is dissipated as shocks from the accreting gas. We show that in order to explain the high surface brightnesses both the mass accretion rate and energy would have to be much higher than expected from simulations or from equating the star formation with the accretion rate. We also investigate scaling relations between the surface brightness expected from accretion and for star formation through mechanical heating and photo-ionization, trying to identify a regime where such accretion may become evident in galaxies. Unfortunately, the surface brightness necessary to detect the gas in optical line emission is about an order of magnitude lower than what has currently been achieved with near-infrared observations of distant galaxies.Comment: 5 pages, 3 figures. Accepted for publication in Astronomy and Astrophysic

Observations and modelling of a clumpy galaxy at z=1.6: Spectroscopic clues to the origin and evolution of chain galaxies

We investigate the properties of a clump-cluster galaxy at redshift 1.57. The morphology of this galaxy is dominated by eight star-forming clumps in optical observations, and has photometric properties typical of most clump-cluster and chain galaxies. Its complex asymmetrical morphology has led to the suggestion that this system is a group merger of several initially separate proto-galaxies. We performed H_alpha integral field spectroscopy of this system using SINFONI on VLT UT4. These observations reveal a large-scale velocity gradient throughout the system, but with large local kinematic disturbances. Using a numerical model of gas-rich disk fragmentation, we find that clump interactions and migration can account for the observed disturbed rotation. On the other hand, the global rotation would not be expected for a multiply merging system. We further find that this system follows the stellar mass vs. metallicity, star formation rate and size relations expected for a disk at this redshift, and exhibits a disk-like radial metallicity gradient, so that the scenario of internal disk fragmentation is the most likely one. A red and metallic central concentration appears to be a bulge in this proto-spiral clumpy galaxy. A chain galaxy at redshift 2.07 in the same field also shows disk-like rotation. Such systems are likely progenitors of the present-day bright spiral galaxies, forming their exponential disks through clump migration and disruption and fueling their bulges. Our present results show that disturbed morphologies and kinematics are not necessarily signs of galaxy mergers and interactions, and can instead result from the internal evolution of primordial disks.Comment: A&A, accepted. Version with full resolution figures available at http://aramis.obspm.fr/~bournaud/udfr2.pdf -- Animation of clumpy galaxy models available at http://aramis.obspm.fr/~bournaud/cc/cc.htm

MASSIV: Mass Assembly Survey with SINFONI in VVDS - II. Kinematics and close environment classification

(Abridged) Processes driving mass assembly are expected to evolve on different timescales along cosmic time. A transition might happen around z ~ 1 as the cosmic star formation rate starts its decrease. Identifying the dynamical nature of galaxies on a representative sample is necessary to infer and compare the mass assembly mechanisms across cosmic time. We present an analysis of the kinematics properties of 50 galaxies with 0.9 < z < 1.6 from the MASSIV sample observed with SINFONI/VLT with 4.5x10^9 Msun < M < 1.7x10^11 Msun and 6 Msun/yr < SFR < 300 Msun/yr. This is the largest sample with 2D-kinematics in this redshift range. We provide a classification based on kinematics as well as on close galaxy environment. We find that 29% of galaxies are experiencing merging or have close companions that may be gravitationally linked. This is placing a lower limit on the fraction of interacting galaxies. We find that at least 44% of the galaxies display ordered rotation whereas at least 35% are non-rotating objects. All rotators except one are compatible with rotation-dominated (Vmax/sigma > 1) systems. Non-rotating objects are mainly small objects (Re < 4 kpc). Combining our sample with other 3D-spectroscopy samples, we find that the local velocity dispersion of the ionized gas component decreases continuously from z ~ 3 to z = 0. The proportion of disks also seems to be increasing in star-forming galaxies when the redshift decreases. The number of interacting galaxies seems to be at a maximum at z ~ 1.2. These results draw a picture in which cold gas accretion may still be efficient at z ~ 1.2 but in which mergers may play a much more significant role at z ~ 1.2 than at higher redshift. From a dynamical point of view, the redshift range 1 < z < 2 therefore appears as a transition period in the galaxy mass assembly process.Comment: 23 pages (+29 maps pages), 7 figures, language corrections and reference updates included, A&A in pres