Risk of Tuberculosis in Dialysis Patients: A Nationwide Cohort Study

Extent: 6p.BACKGROUND: The ability to identify individuals at increased risk of developing tuberculosis (TB) has important implications for public health policy and patient care. We conducted a general population historical cohort study in all Australian States and Territories to establish the risk of TB arising in people on chronic hemo- or peritoneal dialysis. METHODOLOGY/PRINCIPAL FINDINGS: Cases of TB disease in patients receiving chronic dialysis were identified by record linkage using the Australia & New Zealand Dialysis and Transplant Registry (ANZDATA) and State and Territory TB notification databases 2001 to 2006. Main outcome measure was the relative risk of TB in people on dialysis, adjusted for TB incidence in country of birth, sex, age and indigenous status. A total of 6,276 cases of active TB were reported among 19,855,283 people living in Australia between 2001 and 2006. Among 14,506 patients on dialysis, 37 had a notification for TB disease after commencing dialysis, of whom 28 were culture positive. The incidence of TB was 66.8/100,000/year (95% CI 47.7 to 93.2) among people on dialysis and 5.7/100,000/year (95% CI 5.5 to 5.8) in the general population. The adjusted relative risk (aRR) of TB in people on dialysis was 7.8 (95% CI 3.3 to 18.7), and the aRR of culture positive TB was 8.6 (95% CI 3.9 to 19.3). CONCLUSIONS/SIGNIFICANCE: Patients on dialysis are at increased risk of TB. The final decision to screen for, and to treat, LTBI in individual dialysis patients will be influenced by a cumulative assessment of the risk of reactivation of TB and by assessment of risk factors for adverse effects of treatment.Claudia C. Dobler, Stephen P. McDonald and Guy B. Mark

Comparison of cause of death between ANZDATA and the Australian national death index.

Aim: The aim of the present study was to understand the differences in how cause of death for patients receiving renal replacement therapy in Australia is recorded in The Australian and New Zealand Dialysis and Transplant Registry (ANZDATA) compared to the National Death Index (NDI). Methods: Data linkage was performed between ANZDATA and NDI for all deaths in the period 1980-2013. Cause of death was classified according to ICD-10 chapter. Overall and chapter specific agreement were assessed using the Kappa statistic. Descriptive analysis was used to explore differences where there was disagreement on primary cause of death. Results: The analysis cohort included 28 675 patients. Ninety five percent of ANZDATA reported deaths fell within +/- 3 days of the date recorded by NDI. Circulatory death was the most common cause of death in both databases (ANZDATA 48%, NDI 32%). Overall agreement at ICD chapter level of primary cause was poor (36%, kappa 0.22). Agreement was best for malignancy (kappa 0.71). When there was disagreement on primary cause of death these were most commonly coded as genitourinary (35%) and endocrine (25.0%) in NDI, and circulatory (39%) and withdrawal (24%) in ANZDATA. Sixty-nine percent of patients had a renal related cause documented as either primary or a contributing cause of death in the NDI. Conclusion: There is poor agreement in primary cause of death between ANZDATA and NDI which is in part explained by the absence of diabetes and renal failure as causes of death in ANZDATA and the absence of 'withdrawal' in NDI. These differences should be appreciated when interpreting epidemiological data on cause of death in the Australian end stage kidney disease population

The p53Pro72Arg Polymorphism is Associated with Albuminuria among Aboriginal Australians

Albuminuria is a widely recognized marker of renal disease and cardiovascular risk. This is especially true in Aboriginal Australians living in remote communities who suffer high rates of end-stage renal disease and cardiovascular mortality. During a survey of risk factors for renal and cardiovascular disease in one such community, an association between a common polymorphism at codon 72 (Arg/Pro) of the p53 gene and markers of renal disease was sought. A cross-sectional community survey including 217 people was performed. Genotypes of the polymorphism were distributed in Hardy-Weinberg equilibrium, with p53Arg allele frequency of 0.45 (range, 0.41 to 0.50). Overall prevalence of albuminuria was high (31% microalbuminuria; 14% overt albuminuria). Urine albumin/creatinine ratio (ACR) was significantly associated with the number of p53Pro alleles (P = 0.01), and there was an interaction with tobacco smoking (P = 0.04). The p53 genotype was also associated with increasing HbA1c, but the relationship between p53 and ACR was independent of this. This is a previously unreported association. This study does not address the mechanism, but this finding, if confirmed, expands the described effects of p53 in cellular proliferation and apoptosis to include a role in the course of renal and possibly cardiovascular disease in this population

Kidney transplant graft outcomes in 379 257 recipients on 3 continents

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/145422/1/ajt14694_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/145422/2/ajt14694.pd

Detection of Ly\beta auto-correlations and Ly\alpha-Ly\beta cross-correlations in BOSS Data Release 9

The Lyman-$\beta$ forest refers to a region in the spectra of distant quasars that lies between the rest-frame Lyman-$\beta$ and Lyman-$\gamma$ emissions. The forest in this region is dominated by a combination of absorption due to resonant Ly$\alpha$ and Ly$\beta$ scattering. When considering the 1D Ly$\beta$ forest in addition to the 1D Ly$\alpha$ forest, the full statistical description of the data requires four 1D power spectra: Ly$\alpha$ and Ly$\beta$ auto-power spectra and the Ly$\alpha$-Ly$\beta$ real and imaginary cross-power spectra. We describe how these can be measured using an optimal quadratic estimator that naturally disentangles Ly$\alpha$ and Ly$\beta$ contributions. Using a sample of approximately 60,000 quasar sight-lines from the BOSS Data Release 9, we make the measurement of the one-dimensional power spectrum of fluctuations due to the Ly$\beta$ resonant scattering. While we have not corrected our measurements for resolution damping of the power and other systematic effects carefully enough to use them for cosmological constraints, we can robustly conclude the following: i) Ly$\beta$ power spectrum and Ly$\alpha$-Ly$\beta$ cross spectra are detected with high statistical significance; ii) the cross-correlation coefficient is $\approx 1$ on large scales; iii) the Ly$\beta$ measurements are contaminated by the associated OVI absorption, which is analogous to the SiIII contamination of the Ly$\alpha$ forest. Measurements of the Ly$\beta$ forest will allow extension of the usable path-length for the Ly$\alpha$ measurements while allowing a better understanding of the physics of intergalactic medium and thus more robust cosmological constraints.Comment: 26 pages, 10 figures; matches version accepted by JCA

The Linear Theory Power Spectrum from the Lyman-alpha Forest in the Sloan Digital Sky Survey

We analyze the SDSS Ly-alpha forest P_F(k,z) measurement to determine the linear theory power spectrum. Our analysis is based on fully hydrodynamic simulations, extended using hydro-PM simulations. We account for the effect of absorbers with damping wings, which leads to an increase in the slope of the linear power spectrum. We break the degeneracy between the mean level of absorption and the linear power spectrum without significant use of external constraints. We infer linear theory power spectrum amplitude Delta^2_L(k_p=0.009s/km,z_p=3.0)=0.452_{-0.057-0.116}^{+0.069+0.141} and slope n_eff=-2.321_{-0.047-0.102}^{+0.055+0.131} (possible systematic errors are included through nuisance parameters in the fit - a factor >~5 smaller errors would be obtained on both parameters if we ignored modeling uncertainties). The errors are correlated and not perfectly Gaussian, so we provide a chi^2 table to accurately describe the results. The result corresponds to sigma_8=0.85, n=0.94, for a LCDM model with Omega_m=0.3, Omega_b=0.04, and h=0.7, but is most useful in a combined fit with the CMB. The inferred curvature of the linear power spectrum and the evolution of its amplitude and slope with redshift are consistent with expectations for LCDM models, with the evolution of the slope, in particular, being tightly constrained. We use this information to constrain systematic contamination, e.g., fluctuations in the UV background. This paper should serve as a starting point for more work to refine the analysis, including technical improvements such as increasing the size and number of the hydrodynamic simulations, and improvements in the treatment of the various forms of feedback from galaxies and quasars.Comment: Improved presentation, including fit results for (z). Simple code to produce LyaF chi^2 given linear power spectrum available at: http://www.cita.utoronto.ca/~pmcdonal/code.htm

The Lyman-alpha Forest Power Spectrum from the Sloan Digital Sky Survey

We measure the power spectrum, P_F(k,z), of the transmitted flux in the Ly-alpha forest using 3035 high redshift quasar spectra from the Sloan Digital Sky Survey. This sample is almost two orders of magnitude larger than any previously available data set, yielding statistical errors of ~0.6% and ~0.005 on, respectively, the overall amplitude and logarithmic slope of P_F(k,z). This unprecedented statistical power requires a correspondingly careful analysis of the data and of possible systematic contaminations in it. For this purpose we reanalyze the raw spectra to make use of information not preserved by the standard pipeline. We investigate the details of the noise in the data, resolution of the spectrograph, sky subtraction, quasar continuum, and metal absorption. We find that background sources such as metals contribute significantly to the total power and have to be subtracted properly. We also find clear evidence for SiIII correlations with the Ly-alpha forest and suggest a simple model to account for this contribution to the power. While it is likely that our newly developed analysis technique does not eliminate all systematic errors in the P_F(k,z) measurement below the level of the statistical errors, our tests indicate that any residual systematics in the analysis are unlikely to affect the inference of cosmological parameters from P_F(k,z). These results should provide an essential ingredient for all future attempts to constrain modeling of structure formation, cosmological parameters, and theories for the origin of primordial fluctuations.Comment: 92 pages, 45 of them figures, submitted to ApJ, data available at http://feynman.princeton.edu/~pmcdonal/LyaF/sdss.htm

Heme metabolism genes Downregulated in COPD Cachexia.

IntroductionCachexia contributes to increased mortality and reduced quality of life in Chronic Obstructive Pulmonary Disease (COPD) and may be associated with underlying gene expression changes. Our goal was to identify differential gene expression signatures associated with COPD cachexia in current and former smokers.MethodsWe analyzed whole-blood gene expression data from participants with COPD in a discovery cohort (COPDGene, N = 400) and assessed replication (ECLIPSE, N = 114). To approximate the consensus definition using available criteria, cachexia was defined as weight-loss > 5% in the past 12 months or low body mass index (BMI) (< 20 kg/m2) and 1/3 criteria: decreased muscle strength (six-minute walk distance < 350 m), anemia (hemoglobin < 12 g/dl), and low fat-free mass index (FFMI) (< 15 kg/m2 among women and < 17 kg/m2 among men) in COPDGene. In ECLIPSE, cachexia was defined as weight-loss > 5% in the past 12 months or low BMI and 3/5 criteria: decreased muscle strength, anorexia, abnormal biochemistry (anemia or high c-reactive protein (> 5 mg/l)), fatigue, and low FFMI. Differential gene expression was assessed between cachectic and non-cachectic subjects, adjusting for age, sex, white blood cell counts, and technical covariates. Gene set enrichment analysis was performed using MSigDB.ResultsThe prevalence of COPD cachexia was 13.7% in COPDGene and 7.9% in ECLIPSE. Fourteen genes were differentially downregulated in cachectic versus non-cachectic COPD patients in COPDGene (FDR < 0.05) and ECLIPSE (FDR < 0.05).DiscussionSeveral replicated genes regulating heme metabolism were downregulated among participants with COPD cachexia. Impaired heme biosynthesis may contribute to cachexia development through free-iron buildup and oxidative tissue damage