Budesonide Foam Has a Favorable Safety Profile for Inducing Remission in Mild-to-Moderate Ulcerative Proctitis or Proctosigmoiditis.

BackgroundBudesonide foam, a rectally administered, second-generation corticosteroid with extensive hepatic first-pass metabolism, is efficacious for the treatment of mild-to-moderate ulcerative proctitis and ulcerative proctosigmoiditis.AimThe aim of this study was to comprehensively assess the safety and pharmacokinetic profile of budesonide foam.MethodsData from five phase III studies were pooled to further evaluate safety, including an open-label study (once-daily treatment for 8 weeks), an active-comparator study (once-daily treatment for 4 weeks), and two placebo-controlled studies and an open-label extension study (twice-daily treatment for 2 weeks, then once daily for 4 weeks). Data from the placebo-controlled studies and two phase I studies (i.e., patients with mild-to-moderate ulcerative colitis and healthy volunteers) were pooled to evaluate the pharmacokinetics of budesonide foam.ResultsA similar percentage of patients reported adverse events in the budesonide foam and placebo groups, with the majority of adverse events being mild or moderate in intensity (93.3 vs 96.0%, respectively). Adverse events occurred in 41.4 and 36.3% of patients receiving budesonide foam and placebo, respectively. Mean morning cortisol concentrations remained within the normal range for up to 8 weeks of treatment; there were no clinically relevant effects of budesonide foam on the hypothalamic-pituitary-adrenal axis. Population pharmacokinetic analysis demonstrated low systemic exposure after budesonide foam administration.ConclusionsThis integrated analysis demonstrated that budesonide foam for the induction of remission of distal ulcerative colitis is safe overall, with no clinically relevant effects on the hypothalamic-pituitary-adrenal axis

Structural Parameters of the M87 Globular Clusters

We derive structural parameters for ~2000 globular clusters in the giant Virgo elliptical M87 using extremely deep Hubble Space Telescope images in F606W (V) and F814W (I) taken with the ACS/WFC. The cluster scale sizes (half-light radii r_h) and ellipticities are determined from PSF-convolved King-model profile fitting. We find that the r_h distribution closely resembles the inner Milky Way clusters, peaking at r_h~2.5 pc and with virtually no clusters more compact than r_h ~ 1 pc. The metal-poor clusters have on average an r_h 24% larger than the metal-rich ones. The cluster scale size shows a gradual and noticeable increase with galactocentric distance. Clusters are very slightly larger in the bluer waveband V a possible hint that we may be beginning to see the effects of mass segregation within the clusters. We also derived a color magnitude diagram for the M87 globular cluster system which show a striking bimodal distribution.Comment: ApJ accepte

Repeat treatment with rifaximin is safe and effective in patients with diarrhea-predominant irritable bowel syndrome

Background & AimsFew treatments have demonstrated efficacy and safety for diarrhea-predominant irritable bowel syndrome (IBS-D). A phase 3, randomized, double-blind, placebo-controlled trial was performed to evaluate the safety and efficacy of repeat treatment with the nonsystemic antibiotic rifaximin.MethodsThe trial included adults with IBS-D, mean abdominal pain and bloating scores of 3 or more, and loose stool, located at 270 centers in the United States and Europe from February 2012 through June 2014. Those responding to a 2-week course of open-label rifaximin 550 mg 3 times daily, who then relapsed during an observation phase (up to 18 weeks), were randomly assigned to groups given repeat treatments of rifaximin 550 mg or placebo 3 times daily for 2 weeks. The primary end point was percentage of responders after first repeat treatment, defined as a decrease in abdominal pain of ≥30% from baseline and a decrease in frequency of loose stools of ≥50% from baseline, for 2 or more weeks during a 4-week post-treatment period.ResultsOf 1074 patients (44.1%) who responded to open-label rifaximin, 382 (35.6%) did not relapse and 692 (64.4%) did; of these, 636 were randomly assigned to receive repeat treatment with rifaximin (n = 328) or placebo (n = 308). The percentage of responders was significantly greater with rifaximin than placebo (38.1% vs 31.5%; P = .03). The percentage of responders for abdominal pain (50.6% vs 42.2%; P = .018) was significantly greater with rifaximin than placebo, but not stool consistency (51.8% vs 50.0%; P = .42). Significant improvements were also noted for prevention of recurrence, durable response, and bowel movement urgency. Adverse event rates were low and similar between groups.ConclusionsIn a phase 3 study of patients with relapsing symptoms of IBS-D, repeat rifaximin treatment was efficacious and well tolerated. ClinicalTrials.gov ID: NCT01543178

Rifaximin Therapy for Patients with Irritable Bowel Syndrome without Constipation

BACKGROUND Evidence suggests that gut flora may play an important role in the pathophysiology of the irritable bowel syndrome (IBS). We evaluated rifaximin, a minimally absorbed antibiotic, as treatment for IBS. METHODS In two identically designed, phase 3, double-blind, placebo-controlled trials (TARGET 1 and TARGET 2), patients who had IBS without constipation were randomly assigned to either rifaximin at a dose of 550 mg or placebo, three times daily for 2 weeks, and were followed for an additional 10 weeks. The primary end point, the proportion of patients who had adequate relief of global IBS symptoms, and the key secondary end point, the proportion of patients who had adequate relief of IBS-related bloating, were assessed weekly. Adequate relief was defined as self-reported relief of symptoms for at least 2 of the first 4 weeks after treatment. Other secondary end points included the percentage of patients who had a response to treatment as assessed by daily self-ratings of global IBS symptoms and individual symptoms of bloating, abdominal pain, and stool consistency during the 4 weeks after treatment and during the entire 3 months of the study. RESULTS Significantly more patients in the rifaximin group than in the placebo group had adequate relief of global IBS symptoms during the first 4 weeks after treatment (40.8% vs. 31.2%, P=0.01, in TARGET 1; 40.6% vs. 32.2%, P=0.03, in TARGET 2; 40.7% vs. 31.7%, P<0.001, in the two studies combined). Similarly, more patients in the rifaximin group than in the placebo group had adequate relief of bloating (39.5% vs. 28.7%, P=0.005, in TARGET 1; 41.0% vs. 31.9%, P=0.02, in TARGET 2; 40.2% vs. 30.3%, P<0.001, in the two studies combined). In addition, significantly more patients in the rifaximin group had a response to treatment as assessed by daily ratings of IBS symptoms, bloating, abdominal pain, and stool consistency. The incidence of adverse events was similar in the two groups. CONCLUSIONS Among patients who had IBS without constipation, treatment with rifaximin for 2 weeks provided significant relief of IBS symptoms, bloating, abdominal pain, and loose or watery stools. (Funded by Salix Pharmaceuticals; ClinicalTrials.gov numbers, NCT00731679 and NCT00724126.)

N-body models of globular clusters: metallicity, half-light radii and mass-to-light ratios

Size differences of approx. 20% between red (metal-rich) and blue (metal-poor) sub-populations of globular clusters have been observed, generating an ongoing debate as to weather these originate from projection effects or the difference in metallicity. We present direct N-body simulations of metal-rich and metal-poor stellar populations evolved to study the effects of metallicity on cluster evolution. The models start with N = 100000 stars and include primordial binaries. We also take metallicity dependent stellar evolution and an external tidal field into account. We find no significant difference for the half-mass radii of those models, indicating that the clusters are structurally similar. However, utilizing observational tools to fit half-light (or effective) radii confirms that metallicity effects related to stellar evolution combined with dynamical effects such as mass segregation produce an apparent size difference of 17% on average. The metallicity effect on the overall cluster luminosity also leads to higher mass-to-light ratios for metal-rich clusters.Comment: 14 pages, 10 figures, accepted for publication in MNRA

Galaxy Zoo: dust and molecular gas in early-type galaxies with prominent dust lanes

We study dust and associated molecular gas in 352 nearby early-type galaxies (ETGs) with prominent dust lanes. 65% of these `dusty ETGs' (D-ETGs) are morphologically disturbed, suggesting a merger origin. This is consistent with the D-ETGs residing in lower density environments compared to the controls drawn from the general ETG population. 80% of D-ETGs inhabit the field (compared to 60% of the controls) and <2% inhabit clusters (compared to 10% of the controls). Compared to the controls, D-ETGs exhibit bluer UV-optical colours (indicating enhanced star formation) and an AGN fraction that is more than an order of magnitude greater (indicating higher incidence of nuclear activity). The clumpy dust mass residing in large-scale features is estimated, using the SDSS r-band images, to be 10^{4.5}-10^{6.5} MSun. A comparison to the total (clumpy + diffuse) dust masses- calculated using the far-IR fluxes of 15% of the D-ETGs that are detected by the IRAS- indicates that only ~20% of the dust resides in these large-scale features. The dust masses are several times larger than the maximum value expected from stellar mass loss, ruling out an internal origin. The dust content shows no correlation with the blue luminosity, indicating that it is not related to a galactic scale cooling flow. No correlation is found with the age of the recent starburst, suggesting that the dust is accreted directly in the merger rather than being produced in situ by the triggered star formation. Using molecular gas-to-dust ratios of ETGs in the literature we estimate that the median current and initial molecular gas fraction are ~1.3% and ~4%, respectively. Recent work suggests that the merger activity in nearby ETGs largely involves minor mergers (mass ratios between 1:10 and 1:4). If the IRAS-detected D-ETGs form via this channel, then the original gas fractions of the accreted satellites are 20%-44%. [Abridged]Comment: 11 pages, 18 figures, 1 table, MNRAS (Accepted for publication- 2012 March 19

Rifaximin Treatment in Hepatic Encephalopathy

Background Hepatic encephalopathy is a chronically debilitating complication of hepatic cirrhosis. The efficacy of rifaximin, a minimally absorbed antibiotic, is well documented in the treatment of acute hepatic encephalopathy, but its efficacy for prevention of the disease has not been established. Methods In this randomized, double-blind, placebo-controlled trial, we randomly assigned 299 patients who were in remission from recurrent hepatic encephalopathy resulting from chronic liver disease to receive either rifaximin, at a dose of 550 mg twice daily (140 patients), or placebo (159 patients) for 6 months. The primary efficacy end point was the time to the first breakthrough episode of hepatic encephalopathy. The key secondary end point was the time to the first hospitalization involving hepatic encephalopathy. Results Rifaximin significantly reduced the risk of an episode of hepatic encephalopathy, as compared with placebo, over a 6-month period (hazard ratio with rifaximin, 0.42; 95% confidence interval [CI], 0.28 to 0.64; P Conclusions Over a 6-month period, treatment with rifaximin maintained remission from hepatic encephalopathy more effectively than did placebo. Rifaximin treatment also significantly reduced the risk of hospitalization involving hepatic encephalopathy. (ClinicalTrials.gov number, NCT00298038.

A combined low-radio frequency/X-ray study of galaxy groups I. Giant Metrewave Radio Telescope observations at 235 MHz and 610 MHz

We present new Giant Metrewave Radio Telescope observations at 235 MHz and 610 MHz of 18 X-ray bright galaxy groups. These observations are part of an extended project, presented here and in future papers, which combines low-frequency radio and X-ray data to investigate the interaction between central active galactic nuclei (AGN) and the intra-group medium (IGM). The radio images show a very diverse population of group-central radio sources, varying widely in size, power, morphology and spectral index. Comparison of the radio images with Chandra and XMM-Newton X-ray images shows that groups with significant substructure in the X-ray band and marginal radio emission at >= 1 GHz host low-frequency radio structures that correlate with substructures in IGM. Radio-filled X-ray cavities, the most evident form of AGN/IGM interaction in our sample, are found in half of the systems, and are typically associated with small, low- or mid-power double radio sources. Two systems, NGC5044 and NGC4636, possess multiple cavities, which are isotropically distributed around the group center, possibly due to group weather. In other systems the radio/X-ray correlations are less evident. However, the AGN/IGM interaction can manifest itself through the effects of the high-pressure medium on the morphology, spectral properties and evolution of the radio-emitting plasma. In particular, the IGM can confine fading radio lobes in old/dying radio galaxies and prevent them from dissipating quickly. Evidence for radio emission produced by former outbursts that coexist with current activity is found in six groups of the sample.Comment: Accepted for publication in the Astrophysical Journal Supplement Series, 26 pages, 18 figures. A version with high-quality figures is http://www.astro.umd.edu/~simona/giacintucci_hr.pd

Progress report no. 1

Statement of responsibility on title-page reads: Editors: I.A. Forbes, M.J. Driscoll, D.D. Lanning, I. Kaplan, N.C. Rasmussen; Contributors: S.A. Ali, S.T. Brewer, D.K. Choi, F.M. Clikeman, W.R. Corcoran, M.J. Driscoll, I.A. Forbes, C.W. Forsberg, S.L. Ho, C.S. Kang, I. Kaplan, J.L. Klucar, D.D. Lanning, T.C. Leung, E.L. McFarland P.G. Mertens, N.R. Ortiz, A. Pant, N.A. Passman, N.C. Rasmussen, M.K. Sheaffer, D.A. Shupe, G.E. Sullivan, A.T. Supple, J.W. Synan, C.P. Tzanos, W.J. Westlake"MIT-4105-3."Includes bibliographical referencesProgress report; June 30, 1970U.S. Atomic Energy Commission contracts: AT(30-1)410

International meta-analysis of PTSD genome-wide association studies identifies sex- and ancestry-specific genetic risk loci.

The risk of posttraumatic stress disorder (PTSD) following trauma is heritable, but robust common variants have yet to be identified. In a multi-ethnic cohort including over 30,000 PTSD cases and 170,000 controls we conduct a genome-wide association study of PTSD. We demonstrate SNP-based heritability estimates of 5-20%, varying by sex. Three genome-wide significant loci are identified, 2 in European and 1 in African-ancestry analyses. Analyses stratified by sex implicate 3 additional loci in men. Along with other novel genes and non-coding RNAs, a Parkinson's disease gene involved in dopamine regulation, PARK2, is associated with PTSD. Finally, we demonstrate that polygenic risk for PTSD is significantly predictive of re-experiencing symptoms in the Million Veteran Program dataset, although specific loci did not replicate. These results demonstrate the role of genetic variation in the biology of risk for PTSD and highlight the necessity of conducting sex-stratified analyses and expanding GWAS beyond European ancestry populations