On the Expansion Rate, Age, and Distance of the Supernova Remnant G266.2-1.2 (Vela Jr.)

An analysis of Chandra ACIS data for two relatively bright and narrow portions of the northwestern rim of G266.2-1.2 (a.k.a. RX J0852.0-4622 or Vela Jr.) reveal evidence of a radial displacement of 2.40 +/- 0.56 arcsec between 2003 and 2008. The corresponding expansion rate (0.42 +/- 0.10 arcsec/yr or 13.6 +/- 4.2%/kyr) is about half the rate reported for an analysis of XMM-Newton data from a similar, but not identical, portion of the rim over a similar, but not identical, time interval (0.84 +/- 0.23 arcsec/yr, Katsuda et al. 2008a). If the Chandra rate is representative of the remnant as a whole, then the results of a hydrodynamic analysis suggest that G266.2-1.2 is between 2.4 and 5.1 kyr old if it is expanding into a uniform ambient medium (whether or not it was produced by a Type Ia or Type II event). If the remnant is expanding into the material shed by a steady stellar wind, then the age could be as much as 50% higher. The Chandra expansion rate and a requirement that the shock speed be greater than or equal to 1000 km/s yields a lower limit on the distance of 0.5 kpc. An analysis of previously-published distance estimates and constraints suggests G266.2-1.2 is no further than 1.0 kpc. This range of distances is consistent with the distance to the nearer of two groups of material in the Vela Molecular Ridge (0.7 +/- 0.2 kpc, Liseau et al. 1992) and to the Vel OB1 association (0.8 kpc, Eggen 1982).Comment: 30 pages, 7 figure

Population Pharmacokinetics of Methylphenidate in Healthy Adults Emphasizing Novel and Known Effects of Several Carboxylesterase 1 (<i>CES1</i>) Variants

The aim of this study was to identify demographic and genetic factors that significantly affect methylphenidate (MPH) pharmacokinetics (PK), and may help explain interindividual variability and further increase the safety of MPH. d‐MPH plasma concentrations, demographic covariates, and carboxylesterase 1 (CES1) genotypes were gathered from 122 healthy adults and analyzed using nonlinear mixed effects modeling. The structural model that best described the data was a two‐compartment disposition model with absorption transit compartments. Novel effects of rs115629050 and CES1 diplotypes, as well as previously reported effects of rs71647871 and body weight, were included in the final model. Assessment of the independent and combined effect of CES1 covariates identified several specific risk factors that may result in severely increased d‐MPH plasma exposure

Trends in anemia management in US hemodialysis patients 2004-2010.

BACKGROUND: There have been major changes in the management of anemia in US hemodialysis patients in recent years. We sought to determine the influence of clinical trial results, safety regulations, and changes in reimbursement policy on practice. METHODS: We examined indicators of anemia management among incident and prevalent hemodialysis patients from a medium-sized dialysis provider over three time periods: (1) 2004 to 2006 (2) 2007 to 2009, and (3) 2010. Trends across the three time periods were compared using generalized estimating equations. RESULTS: Prior to 2007, the median proportion of patients with monthly hemoglobin >12 g/dL for patients on dialysis 0 to 3, 4 to 6 and 7 to 18 months, respectively, was 42%, 55% and 46% declined to 41%, 54%, and 40% after 2007, and declined more sharply in 2010 to 34%, 41%, and 30%. Median weekly Epoeitin alpha doses over the same periods were 18,000, 12,400, and 9,100 units before 2007; remained relatively unchanged from 2007 to 2009; and decreased sharply in the patients 3-6 and 6-18 months on dialysis to 10,200 and 7,800 units, respectively in 2010. Iron doses, serum ferritin, and transferrin saturation levels increased over time with more pronounced increases in 2010. CONCLUSION: Modest changes in anemia management occurred between 2007 and 2009, followed by more dramatic changes in 2010. Studies are needed to examine the effects of declining erythropoietin use and hemoglobin levels and increasing intravenous iron use on quality of life, transplantation rates, infection rates and survival

Patterns in blood pressure medication use in US incident dialysis patients over the first 6 months.

BACKGROUND: Several observational studies have evaluated the effect of a single exposure window with blood pressure (BP) medications on outcomes in incident dialysis patients, but whether BP medication prescription patterns remain stable or a single exposure window design is adequate to evaluate effect on outcomes is unclear. METHODS: We described patterns of BP medication prescription over 6 months after dialysis initiation in hemodialysis and peritoneal dialysis patients, stratified by cardiovascular comorbidity, diabetes, and other patient characteristics. The cohort included 13,072 adult patients (12,159 hemodialysis, 913 peritoneal dialysis) who initiated dialysis in Dialysis Clinic, Inc., facilities January 1, 2003-June 30, 2008, and remained on the original modality for at least 6 months. We evaluated monthly patterns in BP medication prescription over 6 months and at 12 and 24 months after initiation. RESULTS: Prescription patterns varied by dialysis modality over the first 6 months; substantial proportions of patients with prescriptions for beta-blockers, renin angiotensin system agents, and dihydropyridine calcium channel blockers in month 6 no longer had prescriptions for these medications by month 24. Prescription of specific medication classes varied by comorbidity, race/ethnicity, and age, but little by sex. The mean number of medications was 2.5 at month 6 in hemodialysis and peritoneal dialysis cohorts. CONCLUSIONS: This study evaluates BP medication patterns in both hemodialysis and peritoneal dialysis patients over the first 6 months of dialysis. Our findings highlight the challenges of assessing comparative effectiveness of a single BP medication class in dialysis patients. Longitudinal designs should be used to account for changes in BP medication management over time, and designs that incorporate common combinations should be considered

Cosmic ray diffusion near the Bohm limit in the Cassiopeia A supernova remnant

Supernova remnants (SNRs) are believed to be the primary location of the acceleration of Galactic cosmic rays, via diffusive shock (Fermi) acceleration. Despite considerable theoretical work the precise details are still unknown, in part because of the difficulty in directly observing nucleons that are accelerated to TeV energies in, and affect the structure of, the SNR shocks. However, for the last ten years, X-ray observatories ASCA, and more recently Chandra, XMM-Newton, and Suzaku have made it possible to image the synchrotron emission at keV energies produced by cosmic-ray electrons accelerated in the SNR shocks. In this article, we describe a spatially-resolved spectroscopic analysis of Chandra observations of the Galactic SNR Cassiopeia A to map the cutoff frequencies of electrons accelerated in the forward shock. We set upper limits on the electron diffusion coefficient and find locations where particles appear to be accelerated nearly as fast as theoretically possible (the Bohm limit).Comment: 18 pages, 5 figures. Accepted for publication in Nature Physics (DOI below), final version available week of August 28, 2006 at http://www.nature.com/nphy

Small RNA populations revealed by blocking rRNA fragments in Drosophila melanogaster reproductive tissues

RNA interference (RNAi) is a complex and highly conserved regulatory mechanism mediated via small RNAs (sRNAs). Recent technical advances in high throughput sequencing have enabled an increasingly detailed analysis of sRNA abundances and profiles in specific body parts and tissues. This enables investigations of the localized roles of microRNAs (miRNAs) and small interfering RNAs (siRNAs). However, variation in the proportions of non-coding RNAs in the samples being compared can hinder these analyses. Specific tissues may vary significantly in the proportions of fragments of longer non-coding RNAs (such as ribosomal RNA or transfer RNA) present, potentially reflecting tissue-specific differences in biological functions. For example, in Drosophila, some tissues contain a highly abundant 30nt rRNA fragment (the 2S rRNA) as well as abundant 5’ and 3’ terminal rRNA fragments. These can pose difficulties for the construction of sRNA libraries as they can swamp the sequencing space and obscure sRNA abundances. Here we addressed this problem and present a modified “rRNA blocking” protocol for the construction of high-definition (HD) adapter sRNA libraries, in D. melanogaster reproductive tissues. The results showed that 2S rRNAs targeted by blocking oligos were reduced from >80% to < 0.01% total reads. In addition, the use of multiple rRNA blocking oligos to bind the most abundant rRNA fragments allowed us to reveal the underlying sRNA populations at increased resolution. Side-by-side comparisons of sequencing libraries of blocked and non-blocked samples revealed that rRNA blocking did not change the miRNA populations present, but instead enhanced their abundances. We suggest that this rRNA blocking procedure offers the potential to improve the in-depth analysis of differentially expressed sRNAs within and across different tissues