82 research outputs found

    NGC 5548 in a Low-Luminosity State: Implications for the Broad-Line Region

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    We describe results from a new ground-based monitoring campaign on NGC 5548, the best studied reverberation-mapped AGN. We find that it was in the lowest luminosity state yet recorded during a monitoring program, namely L(5100) = 4.7 x 10^42 ergs s^-1. We determine a rest-frame time lag between flux variations in the continuum and the Hbeta line of 6.3 (+2.6/-2.3) days. Combining our measurements with those of previous campaigns, we determine a weighted black hole mass of M_BH = 6.54 (+0.26/-0.25) x 10^7 M_sun based on all broad emission lines with suitable variability data. We confirm the previously-discovered virial relationship between the time lag of emission lines relative to the continuum and the width of the emission lines in NGC 5548, which is the expected signature of a gravity-dominated broad-line region. Using this lowest luminosity state, we extend the range of the relationship between the luminosity and the time lag in NGC 5548 and measure a slope that is consistent with alpha = 0.5, the naive expectation for the broad line region for an assumed form of r ~ L^alpha. This value is also consistent with the slope recently determined by Bentz et al. for the population of reverberation-mapped AGNs as a whole.Comment: 24 pages, 3 tables, 7 figures, accepted for publication in Ap

    The Mass of the Black Hole in the Seyfert 1 Galaxy NGC 4593 from Reverberation Mapping

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    We present new observations leading to an improved black hole mass estimate for the Seyfert 1 galaxy NGC 4593 as part of a reverberation-mapping campaign conducted at the MDM Observatory. Cross-correlation analysis of the H_beta emission-line light curve with the optical continuum light curve reveals an emission-line time delay of 3.73 (+-0.75) days. By combining this time delay with the H_beta line width, we derive a central black hole mass of M_BH = 9.8(+-2.1)x10^6 M_sun, an improvement in precision of a factor of several over past results.Comment: 22 pages, 3 tables, 5 figures, accepted for publication in Ap

    The Disconnect Between the Guidelines, the Appropriate Use Criteria, and Reimbursement Coverage Decisions The Ultimate Dilemma

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    Recently, the American College of Cardiology Foundation in collaboration with the Heart Rhythm Society published appropriate use criteria (AUC) for implantable cardioverter-defibrillators and cardiac resynchronization therapy. These criteria were developed to critically review clinical situations that may warrant implantation of an implantable cardioverter-defibrillator or cardiac resynchronization therapy device, and were based on a synthesis of practice guidelines and practical experience from a diverse group of clinicians. When the AUC was drafted, the writing committee recognized that some of the scenarios that were deemed “appropriate” or “may be appropriate” were discordant with the clinical requirements of many payers, including the Medicare National Coverage Determination (NCD). To charge Medicare for a procedure that is not covered by the NCD may be construed as fraud. Discordance between the guidelines, the AUC, and the NCD places clinicians in the difficult dilemma of trying to do the “right thing” for their patients, while recognizing that the “right thing” may not be covered by the payer or insurer. This commentary addresses these issues. Options for reconciling this disconnect are discussed, and recommendations to help clinicians provide the best care for their patients are offered

    A Reverberation-Based Mass for the Central Black Hole in NGC 4151

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    We have undertaken a new ground-based monitoring campaign to improve the estimates of the mass of the central black hole in NGC 4151. We measure the lag time of the broad H beta line response compared to the optical continuum at 5100 A and find a lag of 6.6 (+1.1/-0.8) days. We combine our data with the recent reanalysis of UV emission lines by Metzroth et al. to calculate a weighted mean of the black hole mass, M_BH = 4.57 (+0.57/-0.47) x 10^7 M_sun. The absolute calibration of the black hole mass is based on normalization of the AGN black hole mass - stellar velocity dispersion (M_BH - sigma_*) relationship to that of quiescent galaxies by Onken et al. The scatter in the M_BH - sigma_* relationship suggests that reverberation-mapping based mass measurements are typically uncertain by a factor of 3-4.Comment: 17 pages, 3 tables, 3 figures, accepted for publication in Ap

    Primary brain calcification: an international study reporting novel variants and associated phenotypes.

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    Primary familial brain calcification (PFBC) is a rare cerebral microvascular calcifying disorder with a wide spectrum of motor, cognitive, and neuropsychiatric symptoms. It is typically inherited as an autosomal-dominant trait with four causative genes identified so far: SLC20A2, PDGFRB, PDGFB, and XPR1. Our study aimed at screening the coding regions of these genes in a series of 177 unrelated probands that fulfilled the diagnostic criteria for primary brain calcification regardless of their family history. Sequence variants were classified as pathogenic, likely pathogenic, or of uncertain significance (VUS), based on the ACMG-AMP recommendations. We identified 45 probands (25.4%) carrying either pathogenic or likely pathogenic variants (n = 34, 19.2%) or VUS (n = 11, 6.2%). SLC20A2 provided the highest contribution (16.9%), followed by XPR1 and PDGFB (3.4% each), and PDGFRB (1.7%). A total of 81.5% of carriers were symptomatic and the most recurrent symptoms were parkinsonism, cognitive impairment, and psychiatric disturbances (52.3%, 40.9%, and 38.6% of symptomatic individuals, respectively), with a wide range of age at onset (from childhood to 81 years). While the pathogenic and likely pathogenic variants identified in this study can be used for genetic counseling, the VUS will require additional evidence, such as recurrence in unrelated patients, in order to be classified as pathogenic

    A Genetically Encoded Tag for Correlated Light and Electron Microscopy of Intact Cells, Tissues, and Organisms

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    Electron microscopy (EM) achieves the highest spatial resolution in protein localization, but specific protein EM labeling has lacked generally applicable genetically encoded tags for in situ visualization in cells and tissues. Here we introduce “miniSOG” (for mini Singlet Oxygen Generator), a fluorescent flavoprotein engineered from Arabidopsis phototropin 2. MiniSOG contains 106 amino acids, less than half the size of Green Fluorescent Protein. Illumination of miniSOG generates sufficient singlet oxygen to locally catalyze the polymerization of diaminobenzidine into an osmiophilic reaction product resolvable by EM. MiniSOG fusions to many well-characterized proteins localize correctly in mammalian cells, intact nematodes, and rodents, enabling correlated fluorescence and EM from large volumes of tissue after strong aldehyde fixation, without the need for exogenous ligands, probes, or destructive permeabilizing detergents. MiniSOG permits high quality ultrastructural preservation and 3-dimensional protein localization via electron tomography or serial section block face scanning electron microscopy. EM shows that miniSOG-tagged SynCAM1 is presynaptic in cultured cortical neurons, whereas miniSOG-tagged SynCAM2 is postsynaptic in culture and in intact mice. Thus SynCAM1 and SynCAM2 could be heterophilic partners. MiniSOG may do for EM what Green Fluorescent Protein did for fluorescence microscopy

    Rectal Indomethacin Dose Escalation (RIDE) for Prevention of Post-ERCP Pancreatitis in High-Risk Patients: a Randomized Trial

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    Background Although rectal indometacin 100 mg is effective in reducing the frequency and severity of pancreatitis after endoscopic retrograde cholangiopancreatography (ERCP) in high-risk patients, the optimal dose is unknown, and pancreatitis incidence remains high. The aim of this study was to compare the efficacy of two dose regimens of rectal indometacin on the frequency and severity of pancreatitis after ERCP in high-risk patients. Methods In this randomised, double-blind, comparative effectiveness trial, we enrolled patients from six tertiary medical centres in the USA. Eligible patients were those at high risk for the development of pancreatitis after ERCP. We randomly assigned eligible patients (1:1) immediately after ERCP to receive either two 50 mg indometacin suppositories and a placebo suppository (standard-dose group) or three 50 mg indometacin suppositories (high-dose group). 4 h after the procedure, patients assigned to the high-dose group received an additional 50 mg indometacin suppository, whereas patients in the standard-dose group received an additional placebo suppository. The randomisation schedule, stratified according to study centre and with no other restrictions, was computer generated by an investigator who was uninvolved in the clinical care of any participants, distributed to the sites, and kept by personnel not directly involved with the study. These same personnel were responsible for packaging the drug and placebo in opaque envelopes. Patients, study personnel, and treating physicians were masked to study group assignment. The primary outcome of the study was the development of pancreatitis after ERCP. Analyses were done on an intention-to-treat basis. This trial is registered with ClinicalTrials.gov, number NCT01912716, and enrolment is complete. Findings Between July 9, 2013, and March 22, 2018, 1037 eligible patients were enrolled and randomly assigned to receive either standard-dose (n=515) or high-dose indometacin (n=522). Pancreatitis after ERCP occurred in 141 (14%) of 1037 patients—76 (15%) of 515 patients in the standard-dose indometacin group and 65 (12%) of 522 patients in the high-dose indometacin group (risk ratio [RR] 1·19, 95% CI 0·87–1·61; p=0·32). We observed 19 adverse events that were potentially attributable to study drug. Clinically significant bleeding occurred in 14 (1%) of 1037 patients—six (1%) of 515 patients in the standard-dose indometacin group and eight (2%) of 522 patients in the high-dose indometacin group (p=0·79). Three (1%) of 522 patients in the high-dose indometacin group developed acute kidney injury versus none in the standard-dose group (p=0·25). A non-ST elevation myocardial infarction occurred in the standard-dose indometacin group 2 days after ERCP. A transient ischaemic attack occurred in the high-dose indometacin group 5 days after ERCP. All 19 adverse events, in addition to the 141 patients who developed pancreatitis after ERCP, were considered serious as all required admission to hospital. We observed no allergic reactions or deaths at 30 day follow-up. Interpretation Dose escalation to rectal indometacin 200 mg did not confer any advantage compared with the standard 100 mg regimen, with pancreatitis incidence remaining high in high-risk patients. Current practice should continue unchanged. Further research should consider the pharmacokinetics of non-steroidal anti-inflammatory drugs to determine the optimal timing of their administration to prevent pancreatitis after ERCP
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