HST-FOS Observations of M87: Ly-a Emission from the Active Galactic Nucleus

The Faint Object Spectrograph on the Hubble Space Telescope was used to obtain spectra of the central region of M87. These spectra cover the wavelength range 1140 - 1606 Angstrom and have a resolution of about 1 Angstrom. The nuclear continuum is clearly visible in the spectra. The only strong line that is observed is Ly-alpha, which has a velocity width of about 3000 km/sec. There is also a marginal detection of C IV 1549. The ratio of Ly-alpha to C IV in the nuclear spectrum is at least a factor of 2 higher than in a spectrum taken at a position on the disk about 0.6" away from the nucleus by Dopita et al. This enhancement of Ly-alpha at the nucleus could point to significant differences in the properties of the emitting gas and/or the excitation mechanism between the outer and inner disk regions. The strength of the observed Ly-alpha places limits on the properties of the absorbing gas present within M87. For instance, if the hydrogen column at the systemic velocity of M87 is greater than about 10^18 cm^{-2} then it can cover only a small fraction of the line emitting region. Spectra separated by 5 days show a 60% difference in the Ly-alpha flux, but the same continuum level. This could be due to either a displacement between the aperture positions for the two sets of observations, or it could be due to intrinsic variability of the source. The current observations do not strongly favor either of these alternatives. The observations do show, however, that the Ly-alpha line is a useful tracer of kinematics in the M87 nucleus.Comment: 14 pages + 5 figures. LaTeX uses aaspp4.sty. Accepted for publication in the Astrophysical Journa

Selection for Greater β-Glucan Content in Oat Grain

Oat (Avena sativa L.) β-glucan lowers serum cholesterol in humans. Development of oat cultivars with greater groat (caryopsis) β-glucan content would increase the nutritional and economic value of the crop. The objectives of this experiment were to evaluate the response to phenotypic selection among individual S0 plants for greater groat β-glucan content in two genetically broad-based populations; to compare selected experimental lines to standard check cultivars; and to estimate genetic variances and heritabilities and to test for nonadditive genetic variance for β-glucan content. We measured groat β-glucan contents of check cultivars and parental lines and random S0:1 lines from initial and selected generations of each population grown in field experiments in 1996 and 1997 at two Iowa locations. Mean β-glucan content increased from 53.9 to 59.9 g kg−1 in one population, and from 63.5 to 66.0 g kg−1 in the other, following selection. Genetic variance of β-glucan content decreased by 9 to 22% following selection, but heritability for β-glucan content did not change significantly. Heritability estimates ranged from 0.80 to 0.85 on a line mean basis. Additive variance was the only substantial component of genetic variance. Some experimental lines had significantly greater β-glucan content than the best check cultivars and lines. Phenotypic selection for greater groat β-glucan content will be effective for developing cultivars with elevated β-glucan contents

Bandpass Dependence of X-ray Temperatures in Galaxy Clusters

We explore the band dependence of the inferred X-ray temperature of the intracluster medium (ICM) for 192 well-observed galaxy clusters selected from the Chandra Data Archive. If the hot ICM is nearly isothermal in the projected region of interest, the X-ray temperature inferred from a broad-band (0.7-7.0 keV) spectrum should be identical to the X-ray temperature inferred from a hard-band (2.0-7.0 keV) spectrum. However, if unresolved cool lumps of gas are contributing soft X-ray emission, the temperature of a best-fit single-component thermal model will be cooler for the broad-band spectrum than for the hard-band spectrum. Using this difference as a diagnostic, the ratio of best-fitting hard-band and broad-band temperatures may indicate the presence of cooler gas even when the X-ray spectrum itself may not have sufficient signal-to-noise to resolve multiple temperature components. To test this possible diagnostic, we extract X-ray spectra from core-excised annular regions for each cluster in our archival sample. We compare the X-ray temperatures inferred from single-temperature fits when the energy range of the fit is 0.7-7.0 keV (broad) and when the energy range is 2.0/(1+z)-7.0 keV (hard). We find that the hard-band temperature is significantly higher, on average, than the broad-band temperature. Upon further exploration, we find this temperature ratio is enhanced preferentially for clusters which are known merging systems. In addition, cool-core clusters tend to have best-fit hard-band temperatures that are in closer agreement with their best-fit broad-band temperatures. We show, using simulated spectra, that this diagnostic is sensitive to secondary cool components (TX = 0.5-3.0 keV) with emission measures >10-30% of the primary hot component.Comment: Accepted for publication in Ap

Methodology of a reevaluation of cardiovascular outcomes in the RECORD trial: study design and conduct

Background In 2010, after regulatory review of rosiglitazone licensing, the US Food and Drug Administration (FDA) requested a reevaluation of cardiovascular end points in the RECORD trial.<p></p> Methods Automated screening of the original clinical trial database and manual case report form review were performed to identify all potential cardiovascular and noncardiovascular deaths, and nonfatal myocardial infarction (MI) and stroke events. Search techniques were used to find participants lost to follow-up, and sites were queried for additional source documents. Suspected events underwent blinded adjudication using both original RECORD end point definitions and new FDA end point definitions, before analysis by the Duke Clinical Research Institute.<p></p> Results The reevaluation effort included an additional 328 person-years of follow-up. Automated screening identified 396 suspected deaths, 2,052 suspected MIs, and 468 suspected strokes. Manual review of documents by Duke Clinical Research Institute clinical events classification (CEC) coordinators identified an additional 31 suspected deaths, 49 suspected MIs, and 28 suspected strokes. There were 127 CEC queries issued requesting additional information on suspected deaths; 43 were closed with no site response, 61 were closed with a response that no additional data were available, and additional data were received for 23. Seventy CEC queries were issued requesting additional information for suspected MI and stroke events; 31 were closed with no site response, 20 were closed with a response that no additional data were available, and 19 resulted in additional data.<p></p> Conclusions Comprehensive procedures were used for rigorous event reascertainment and readjudication in a previously completed open-label, global clinical trial. These procedures used in this unique situation were consistent with other common approaches in the field, were enhanced to address the FDA concerns about the original RECORD trial results, and could be considered by clinical trialists designing event readjudication protocols for drug development programs that have been completed.<p></p&gt

Results of a reevaluation of cardiovascular outcomes in the RECORD trial

Background The US Food and Drug Administration (FDA) required a reevaluation of cardiovascular (CV) outcomes in the RECORD trial. This provided an opportunity to assess the implications of event adjudication by 2 groups and quantify the differences as well as to use new FDA end point definitions in development.<p></p> Methods Original data were used to systematically identify all potential deaths, myocardial infarctions (MIs), and strokes. Site investigators were approached for additional source documents and information about participants lost to follow-up. Suspected events were adjudicated using standard procedures, and the results were compared with the original trial outcomes.<p></p> Results Follow-up for mortality was 25,833 person-years, including an additional 328 person-years identified during the reevaluation effort. A total of 184 CV or unknown-cause deaths (88 rosiglitazone, 96 metformin/sulfonylurea), 128 participants with an MI (68 rosiglitazone, 60 metformin/sulfonylurea), and 113 participants with a stroke (50 rosiglitazone, 63 metformin/sulfonylurea) were included. The hazard ratio (HR) for rosiglitazone versus metformin/sulfonylurea for the end point of CV (or unknown cause) death, MI, or stroke was 0.95 (95% CI 0.78-1.17) compared with 0.93 (95% CI 0.74-1.15) for the original RECORD results. Treatment comparisons for MI (HR 1.13, 95% CI 0.80-1.59) and mortality (HR 0.86, 95% CI 0.68-1.08) were also the same compared with the original RECORD results. Sensitivity analyses were also consistent with the original RECORD results. Analyses using the FDA definitions showed similar results.<p></p> Conclusions Only a modest number of additional person-years of follow-up were ascertained from this reevaluation of CV end points in RECORD. Observed HRs and CIs from these analyses using the original RECORD or new FDA end point definitions showed similar treatment effects of rosiglitazone compared with the original RECORD results.<p></p&gt

Yorkie Promotes Transcription by Recruiting a Histone Methyltransferase Complex

SummaryHippo signaling limits organ growth by inhibiting the transcriptional coactivator Yorkie. Despite the key role of Yorkie in both normal and oncogenic growth, the mechanism by which it activates transcription has not been defined. We report that Yorkie binding to chromatin correlates with histone H3K4 methylation and is sufficient to locally increase it. We show that Yorkie can recruit a histone methyltransferase complex through binding between WW domains of Yorkie and PPxY sequence motifs of NcoA6, a subunit of the Trithorax-related (Trr) methyltransferase complex. Cell culture and in vivo assays establish that this recruitment of NcoA6 contributes to Yorkie’s ability to activate transcription. Mammalian NcoA6, a subunit of Trr-homologous methyltransferase complexes, can similarly interact with Yorkie’s mammalian homolog YAP. Our results implicate direct recruitment of a histone methyltransferase complex as central to transcriptional activation by Yorkie, linking the control of cell proliferation by Hippo signaling to chromatin modification

Randomized trial comparing proactive, high-dose versus reactive, low-dose intravenous iron supplementation in hemodialysis (PIVOTAL) : Study design and baseline data

Background: Intravenous (IV) iron supplementation is a standard maintenance treatment for hemodialysis (HD) patients, but the optimum dosing regimen is unknown. Methods: PIVOTAL (Proactive IV irOn Therapy in hemodiALysis patients) is a multicenter, open-label, blinded endpoint, randomized controlled (PROBE) trial. Incident HD adults with a serum ferritin 700 μg/L and/or TSAT ≥40%) or a reactive, low-dose IV iron arm (iron sucrose administered if ferritin <200 μg/L or TSAT < 20%). We hypothesized that proactive, high-dose IV iron would be noninferior to reactive, low-dose IV iron for the primary outcome of first occurrence of nonfatal myocardial infarction (MI), nonfatal stroke, hospitalization for heart failure or death from any cause. If noninferiority is confirmed with a noninferiority limit of 1.25 for the hazard ratio of the proactive strategy relative to the reactive strategy, a test for superiority will be carried out. Secondary outcomes include infection-related endpoints, ESA dose requirements, and quality-of-life measures. As an event-driven trial, the study will continue until at least 631 primary outcome events have accrued, but the expected duration of follow-up is 2-4 years. Results: Of the 2,589 patients screened across 50 UK sites, 2,141 (83%) were randomized. At baseline, 65.3% were male, the median age was 65 years, and 79% were white. According to eligibility criteria, all patients were on ESA at screening. Prior stroke and MI were present in 8 and 9% of the cohort, respectively, and 44% of patients had diabetes at baseline. Baseline data for the randomized cohort were generally concordant with recent data from the UK Renal Registry. Conclusions: PIVOTAL will provide important information about the optimum dosing of IV iron in HD patients representative of usual clinical practice. Trial Registration: EudraCT number: 2013-002267-25.Peer reviewedFinal Published versio

Comparative ergonomic workflow and user experience analysis of MRI versus fluoroscopy-guided vascular interventions:an iliac angioplasty exemplar case study

Purpose A methodological framework is introduced to assess and compare a conventional fluoroscopy protocol for peripheral angioplasty with a new magnetic resonant imaging (MRI)-guided protocol. Different scenarios were considered during interventions on a perfused arterial phantom with regard to time-based and cognitive task analysis, user experience and ergonomics. Methods Three clinicians with different expertise performed a total of 43 simulated common iliac angioplasties (9 fluoroscopic, 34 MRI-guided) in two blocks of sessions. Six different configurations for MRI guidance were tested in the first block. Four of them were evaluated in the second block and compared to the fluoroscopy protocol. Relevant stages’ durations were collected, and interventions were audio-visually recorded from different perspectives. A cued retrospective protocol analysis (CRPA) was undertaken, including personal interviews. In addition, ergonomic constraints in the MRI suite were evaluated. Results Significant differences were found when comparing the performance between MRI configurations versus fluoroscopy. Two configurations [with times of 8.56 (0.64) and 9.48 (1.13) min] led to reduce procedure time for MRI guidance, comparable to fluoroscopy [8.49 (0.75) min]. The CRPA pointed out the main influential factors for clinical procedure performance. The ergonomic analysis quantified musculoskeletal risks for interventional radiologists when utilising MRI. Several alternatives were suggested to prevent potential low-back injuries. Conclusions This work presents a step towards the implementation of efficient operational protocols for MRI-guided procedures based on an integral and multidisciplinary framework, applicable to the assessment of current vascular protocols. The use of first-user perspective raises the possibility of establishing new forms of clinical training and education