Predicting chronic renal insufficiency in idiopathic membranous glomerulonephritis

Predicting chronic renal insufficiency in idiopathic membranous glomerulonephritis. We developed an approach in quantifying the risk of developing chronic renal insufficiency (CRI) based on a cohort of 184 patients with idiopathic membranous glomerulonephritis (IMGN), prospectively followed by the Toronto Glomerulonephritis Registry between 1974 and 1988. After a mean follow-up period of 5.8 years, 26% of patients developed CRI (defined as persistent reduction of creatinine clearance (CCr) ≤ 60 ml/min/1.73m2 for ≥12 months). We found that when compared to the baseline probability of the unselected patients, the severity of proteinuria at kidney biopsy added only marginally to the prediction of CRI. We introduced a special test condition: persistent proteinuria (PP) (that is, duration of proteinuria, g/day, above different cut-off levels). We examined the positive predictive value (PPV) and sensitivity (SEN) of 15 arbitrarily chosen levels of PP (that is, proteinuria ≥4, 6 or 8 g/day persisting for ≥6, 9, 12, 18 or 24 months) to select levels with optimal predictive characteristics. We found that PP ≥ 8 g/day for ≥six months was a simple and useful predictor of CRI with a PPV and SEN of 66%. To further improve our prediction, we tested the following parameters: age, sex, initial SCr and CCr, proteinuria, serum albumin, hypertension, rate of change of CCr over time, and therapy (steroids ± immunosuppressive drugs) in a multivariate analysis. Proteinuria, initial CCr, and rate of change of CCr were most important in predicting CRI. Fifteen models were then developed by including each patient's CCr at the start of PP and its rate of change during the time period selected. Two models based on PP ≥ 4 g/day for ≥18 months, or ≥6 g/day for ≥9 months significantly improved the PPV's for CRI from those based on the same levels of PP alone. Using these test conditions, we can improve the prediction of CRI from a baseline probability of 26% in unselected patients to a range of 55 to 86% in the “high-risk” patients (with SEN > 60%). Application of these predictive strategies in IMGN will be useful in managing the individual patients and in selecting patients for clinical trials by limiting the exposure of potentially toxic therapy to the “high-risk” patients

Searching for Dust Reddening in SDSS Spectra with Damped Lyman α\alpha{} Systems

We searched for evidence of reddening of background SDSS QSO spectra due to dust in intervening DLA systems. We utilise the Data Releases 5 and 7 to arrive at sample sizes of 475 (DR5) and 676 (DR7) absorbers, based on two different published lists of SDSS DLAs. Both samples span roughly the redshift range of 2.2 < z_abs < 5.2, with a mean of z~3.0, and the majority of the DLAs (75%) below z=3.3. We construct geometric mean spectra in the absorber restframes ranging from 1240 to ~2800 A, and composite spectra of samples matching the 'DLA' QSOs in i band magnitude and emission redshift z_em, but without absorption lines. By comparing the slopes of these composite spectra with their matched counterparts, we find no sign of reddening in the ensemble of the absorbers from these samples. Owing to both the unprecedently large sizes of the DLA samples themselves and the non-DLA SDSS QSO sample, from which we can draw our matching spectra, we can place very tight limits for this non-detection ( =-0.0013+-0.0025 (DR5) and =-0.0017+-0.0022 (DR7). Interestingly, when applying our technique to the samples of York et. al. (2006), vandenBerk et al. (2008) (intervening and intrinsic MgII absorbers) and the smaller DLA-subsample and pool of comparison QSOs of Vladilo et al. (2008), we do recover their results, i.e. detect the same amount of reddening as these authors do. Furthermore, we have tested whether subsamples of our large sample in categories involving the absorbers (HI column densities, presence or absence of accompanying metal absorption, absorber redshift) or the background quasars (emission redshift, brightness) do reveal dust extinction, but found no trends. These results are at odds with both detections of dust reddening from previous studies, and also with expectations from observations of high-redshift galaxies. (abridged)Comment: 16 pages, 12 figures, accepted for publication in MNRA

Exploring the dust content of SDSS DR7 damped Lyman alpha systems at 2.15≤zab<\le z_{ab}< 5.2

We have studied a sample of 1084 intervening absorption systems with 2.15$\le z_{ab}\le$5.2, having log(N$_{\rm HI}$) $>$ 20.0 in the spectra of QSOs in Sloan Digital Sky Survey (SDSS) data release 7 (DR7), with the aim of understanding the nature and abundance of the dust and the chemical abundances in the DLA absorbers. Composite spectra were constructed for the full sample and several subsamples, chosen on the basis of absorber and QSO properties. Average extinction curves were obtained for the samples by comparing their geometric mean composite spectra with those of two samples of QSOs, matching in z$_{em}$ and i magnitude with the DLA sample, one sample without any absorbers along their lines of sight and the other without any DLAs along their lines of sight irrespective of the presence of other absorption systems. While the average reddening in the DLA sample is small, we find definite evidence for the presence of dust in subsamples based on absorber properties, in particular the strength of metal absorption lines. DLAs along lines of sight to QSOs which are not colour selected are found to be more dusty compared to those along the lines of sight to the more numerous colour selected QSOs. From these studies and from the strengths of absorption lines in the composite spectra, we conclude that $\le$ 10% of the DLAs in SDSS DR7 cause significant reddening, have stronger absorption lines and have higher abundances as compared to the rest of the sample. The rest of the sample shows little reddening. Due to the dominant color selection method used to target QSOs in the SDSS DR7, this fraction of 10% likely represents a lower limit for the global fraction of dusty DLAs at high-z.Comment: 12 pages, 9 figures. To appear in MNRA

A missense mutation in PKD1 attenuates the severity of renal disease

Mutations of PKD1 and PKD2 account for most cases of autosomal dominant polycystic kidney disease (ADPKD). Compared with PKD2, patients with PKD1 typically have more severe renal disease. Here, we report a follow-up study of a unique multigeneration family with bilineal ADPKD (NFL10) in which a PKD1 disease haplotype and a PKD2 (L736X) mutation co-segregated with 18 and 14 affected individuals, respectively. In our updated genotype–phenotype analysis of the family, we found that PKD1-affected individuals had uniformly mild renal disease similar to the PKD2-affected individuals. By sequencing all the exons and splice junctions of PKD1, we identified two missense mutations (Y528C and R1942H) from a PKD1-affected individual. Although both variants were predicted to be damaging to the mutant protein, only Y528C co-segregated with all of the PKD1-affected individuals in NFL10. Studies in MDCK cells stably expressing wild-type and mutant forms of PKD found that cell lines expressing the Y528C variant formed cysts in culture and displayed increased rates of growth and apoptosis. Thus, Y528C functions as a hypomorphic PKD1 allele. These findings have important implications for pathogenic mechanisms and molecular diagnostics of ADPKD

Cosmological Information from Quasar-Galaxy Correlations induced by Weak Lensing

The magnification bias of large-scale structures, combined with galaxy biasing, leads to a cross-correlation of distant quasars with foreground galaxies on angular scales of the order of arc minutes and larger. The amplitude and angular shape of the cross-correlation function w_QG contain information on cosmological parameters and the galaxy bias factor. While the existence of this cross-correlation has firmly been established, existing data did not allow an accurate measurement of w_QG yet, but wide area surveys like the Sloan Digital Sky Survey now provide an ideal database for measuring it. However, w_QG depends on several cosmological parameters and the galaxy bias factor. We study in detail the sensitivity of w_QG to these parameters and develop a strategy for using the data. We show that the parameter space can be reduced to the bias factor b, Omega_0 and sigma_8, and compute the accuracy with which these parameters can be deduced from SDSS data. Under reasonable assumptions, it should be possible to reach relative accuracies of the order of 5%-15% for b, Omega_0, and sigma_8. This method is complementary to other weak-lensing analyses based on cosmic shear.Comment: 11 pages, 7 figures, accepted for publication in Astronomy and Astrophysic

Measuring Omega_0 with higher-order Quasar-Galaxy Correlations induced by Weak Lensing

Via the magnification bias, gravitational lensing by large-scale structures causes angular cross-correlations between distant quasars and foreground galaxies on angular scales of arc minutes and above. We investigate the three-point cross-correlation between quasars and galaxy pairs measurable via the second moment of the galaxy counts around quasars and show that it reaches the level of a few per cent on angular scales near one arc minute. Combining two- and three-point correlations, a skewness parameter can be defined which is shown to be virtually independent on the shape and normalisation of the dark-matter power spectrum. If the galaxy bias is linear and deterministic, the skewness depends on the cosmic matter density parameter Omega_0 only; otherwise, it can be used to probe the linearity and stochasticity of the bias. We finally estimate the signal-to-noise ratio of a skewness determination and find that around twenty thousand distant quasars e.g. from the Sloan Digital Sky Survey should suffice for a direct measurement of Omega_0.Comment: 11 pages, 6 figures, submitted to Astronomy and Astrophysic

The color excess of quasars with intervening DLA systems- Analysis of the SDSS data release five

We analyzed the spectroscopic and photometric database of the 5th data release of the Sloan Digital Sky Survey (SDSS) to search for evidence of the quasar reddening produced by dust embedded in intervening damped Ly alpha (DLA) systems. From a list of 5164 quasars in the interval of emission redshift 2.25 /= 4, we built up an "absorption sample" of 248 QSOs with a single DLA system in the interval of absorption redshift 2.2 < z_a </= 3.5 and a "pool" of 1959 control QSOs without DLA systems or strong metal systems. For each QSO of the absorption sample we extracted from the pool a subset of control QSOs that are closest in redshift and magnitude. The mean color of this subset was used as a zero point to measure the "deviation from the mean color" of individual DLA-QSOs, Delta_i. The colors were measured using "BEST" ugriz SDSS imaging data. The mean color excess of the absorption sample, , was estimated by averaging the individual color deviations Delta_i. We find = 27 +/- 9 x 10**(-3) mag and = 54 +/- 12 x 10**(-3) mag. These values are representative of the reddening of DLA systems at z_a ~ 2.7 in SDSS QSOs with limiting magnitude r =/~ 20.2. The detection of the mean reddening is confirmed by several statistical tests. Analysis of the results suggests an origin of the reddening in dust embedded in the DLA systems, with an SMC-type extinction curve. By converting the reddening into rest-frame extinction, we derive a mean dust-to-gas ratio ~ 2 to 4 x 10**(-23) mag cm^2. This value is ~ -1.25 dex lower than the mean dust-to-gas ratio of the Milky Way, in line with the lower level of metallicity in the present DLA sample.Comment: Accepted for publication on Astronomy & Astrophysics, 17 pages, 10 figure

Metallicities and dust content of proximate damped Lyman alpha systems in the Sloan Digital Sky Survey

Composite spectra of 85 proximate absorbers (log N(HI)>20 and velocity difference between the absorption and emission redshift, dv<10,000 km/s) in the SDSS are used to investigate the trends of metal line strengths with velocity separation from the QSO. We construct composites in 3 velocity bins: dv<3000 km/s, 30006000 km/s, with further sub-samples to investigate the metal line dependence on N(HI) and QSO luminosity. Low (e.g. SiII and FeII) and high ionization (e.g. SiIV and CIV) species alike have equivalent widths (EWs) that are larger by factors of 1.5 -- 3 in the dv<3000 km/s composite, compared to the dv>6000 km/s spectrum. The EWs show an even stronger dependence on dv if only the highest neutral hydrogen column density (log N(HI)>20.7) absorbers are considered. We conclude that PDLAs generally have higher metallicities than intervening absorbers, with the enhancement being a function of both dv and N(HI). It is also found that absorbers near QSOs with lower rest-frame UV luminosities have significantly stronger metal lines. We speculate that absorbers near to high luminosity QSOs may have had their star formation prematurely quenched. Finally, we search for the signature of dust reddening by the PDLAs, based on an analysis of the QSO continuum slopes relative to a control sample and determine a limit of E(B-V)<0.014 for an SMC extinction curve. This work provides an empirical motivation for distinguishing between proximate and intervening DLAs, and establishes a connection between the QSO environment and galaxy properties at high redshifts.Comment: Accepted for publication in MNRA