Possible X-ray diagnostic for jet/disk dominance in Type 1 AGN

Using Rossi X-ray Timing Explorer Seyfert 1 and 1.2 data spanning 9 years, we study correlations between X-ray spectral features. The sample consists of 350 time-resolved spectra from 12 Seyfert 1 and 1.2 galaxies. Each spectrum is fitted to a model with an intrinsic powerlaw X-ray spectrum produced close to the central black hole that is reprocessed and absorbed by material around the black hole. To test the robustness of our results, we performed Monte Carlo simulations of the spectral sample. We find a complex relationship between the iron line equivalent width (EW) and the underlying power law index (Gamma). The data reveal a correlation between Gamma and EW which turns over at Gamma <~ 2, but finds a weak anti-correlation for steeper photon indices. We propose that this relationship is driven by dilution of a disk spectrum (which includes the narrow iron line) by a beamed jet component and, hence, could be used as a diagnostic of jet-dominance. In addition, our sample shows a strong correlation between the reflection fraction (R) and Gamma, but we find that it is likely the result of modeling degeneracies. We also see the X-ray Baldwin effect (an anti-correlation between the 2-10 keV X-ray luminosity and EW) for the sample as a whole, but not for the individual galaxies and galaxy types.Comment: Accepted for publication in ApJ, 14 page

Noninvasive Sphenopalatine Ganglion Block for Acute Headache in the Emergency Department: A Randomized Placebo-Controlled Trial

Study objective We seek to test the efficacy of noninvasive sphenopalatine ganglion block for the treatment of acute anterior headache in the emergency department (ED) using a novel noninvasive delivery device. Methods We conducted a randomized, double-blind, placebo-controlled trial evaluating bupivacaine anesthesia of the sphenopalatine ganglion for acute anterior or global-based headache. This study was completed in 2 large academic EDs. Bupivacaine or normal saline solution was delivered intranasally (0.3 mL per side) with the Tx360 device. Pain and nausea were measured at 0, 5, and 15 minutes by a 100-mm visual analog scale. The primary endpoint was a 50% reduction in pain at 15 minutes. Telephone follow-up assessed 24-hour pain and nausea through a 0- to 10-point verbal scale and adverse effects. Results The median reported baseline pain in the bupivacaine group was 80 mm (IQR 66 mm - 93 mm) and 78.5 mm (IQR 64 mm to 91.75 mm) in the normal saline solution group. A 50% reduction in pain was achieved in 48.8% of the bupivacaine group (20/41 patients) versus 41.3% in the normal saline solution group (19/46 patients), for an absolute risk difference of 7.5% (95% confidence interval [CI] –13% to 27.1%). As a secondary outcome, at 24 hours, more patients in the bupivacaine group were headache free (24.7% difference; 95% CI 2.6% to 43.6%) and more were nausea free (16.9% difference; 95% CI 0.8% to 32.5%). Conclusion For patients with acute anterior headache, sphenopalatine ganglion block with the Tx360 device with bupivacaine did not result in a significant increase in the proportion of patients achieving a greater than or equal to 50% reduction in headache severity at 15 minutes compared with saline solution applied in the same manner

Serum Bovine Immunoglobulins Improve Inflammation and Gut Barrier Function in Persons with HIV and Enteropathy on Suppressive ART.

BackgroundSystemic inflammation persists in chronic HIV infection and is associated with increased rates of non-AIDS events such as cardiovascular and liver disease. Increased gut permeability and systemic exposure to microbial products are key drivers of this inflammation. Serum-derived bovine immunoglobulin/protein isolate (SBI) supports gut healing in other conditions such as inflammatory bowel disease.MethodsIn this randomized, double-blind study, participants receiving suppressive antiretroviral therapy (ART) with chronic diarrhea received placebo or SBI at 2.5 g BID or 5 g BID for 4 weeks, followed by a 20-week placebo-free extension phase with SBI at either 2.5 or 5 g BID. Intestinal fatty acid binding protein (I-FABP), zonulin, flagellin, lipopolysaccharide (LPS) and LPS-binding protein, and inflammatory markers were measured by ELISA or multiplex assays. Non-parametric tests were used for analysis.ResultsOne hundred three participants completed the study. By week 24 SBI significantly decreased circulating levels of I-FABP (-0.35 ng/μL, P=0.002) and zonulin (-4.90 ng/μL, P=0.003), suggesting improvement in gut damage, and interleukin-6 (IL-6) (-0.40 pg/μL, P=0.002), reflecting improvement in systemic inflammation. In participants with the lowest quartile of CD4+ T-cell counts at baseline (189-418 cells/μL), CD4+ T-cell counts increased significantly (26 cells/μL; P=0.002).ConclusionsOral SBI may decrease inflammation and warrants further exploration as a potential strategy to improve gut integrity and decrease systemic inflammation among persons receiving prolonged suppressive ART

Relativistic Broadening of Iron Emission Lines in a Sample of AGN

We present a uniform X-ray spectral analysis of eight type-1 active galactic nuclei (AGN) that have been previously observed with relativistically broadened iron emission lines. Utilizing data from the XMM-Newton European Photon Imaging Camera (EPIC-pn) we carefully model the spectral continuum, taking complex intrinsic absorption and emission into account. We then proceed to model the broad Fe K feature in each source with two different accretion disk emission line codes, as well as a self-consistent, ionized accretion disk spectrum convolved with relativistic smearing from the inner disk. Comparing the results, we show that relativistic blurring of the disk emission is required to explain the spectrum in most sources, even when one models the full reflection spectrum from the photoionized disk.Comment: 50 pages (preprint format), 24 figures. Accepted by Ap

Mobile integrated health to reduce post-discharge acute care visits: A pilot study

Background Mobile Integrated Health (MIH) leverages specially trained paramedics outside of emergency response to bridge gaps in local health care delivery. Study objective To evaluate the efficacy of a MIH led transitional care strategy to reduce acute care utilization. Methods This was a retrospective cohort analysis of a quality improvement pilot of patient patients from an urban, single county EMS, MIH transitional care initiative. We utilized a paramedic/social worker (or social care coordinator) dyad to provide in home assessments, medication review, care coordination, and improve access to care. The primary outcome compared acute care utilization (ED visits, observation stays, inpatient visits) 90 days before MIH intervention to 90 days after. Results Of the 203 patients seen by MIH teams, inpatient utilization decreased significantly from 140 hospitalizations pre-MIH to 26 post-MIH (83% reduction, p = 0.00). ED and observation stays, however, increased numerically, but neither was significant. (ED 18 to 19 stays, p = 0.98; observation stays 95 to 106, p = 0.30) Primary care visits increased 15% (p = 0.11). Conclusion In this pilot before/after study, MIH significantly reduces acute care hospitalizations

Investigation of pulsed laser induced dewetting in nanoscopic metal films

Hydrodynamic pattern formation (PF) and dewetting resulting from pulsed laser induced melting of nanoscopic metal films have been used to create spatially ordered metal nanoparticle arrays with monomodal size distribution on SiO_{\text{2}}/Si substrates. PF was investigated for film thickness h\leq7 nm < laser absorption depth \sim11 nm and different sets of laser parameters, including energy density E and the irradiation time, as measured by the number of pulses n. PF was only observed to occur for E\geq E_{m}, where E_{m} denotes the h-dependent threshold energy required to melt the film. Even at such small length scales, theoretical predictions for E_{m} obtained from a continuum-level lumped parameter heat transfer model for the film temperature, coupled with the 1-D transient heat equation for the substrate phase, were consistent with experimental observations provided that the thickness dependence of the reflectivity of the metal-substrate bilayer was incorporated into the analysis. The spacing between the nanoparticles and the particle diameter were found to increase as h^{2} and h^{5/3} respectively, which is consistent with the predictions of the thin film hydrodynamic (TFH) dewetting theory. These results suggest that fast thermal processing can lead to novel pattern formation, including quenching of a wide range of length scales and morphologies.Comment: 36 pages, 11 figures, 1 tabl

Species D Adenoviruses as Oncolytics against B-cell Cancers

Purpose: Oncolytic viruses are self-amplifying anticancer agents that make use of the natural ability of viruses to kill cells. Adenovirus serotype 5 (Ad5) has been extensively tested against solid cancers, but less so against B-cell cancers because these cells do not generally express the coxsackie and adenoviral receptor (CAR). To determine whether other adenoviruses might have better potency, we mined the adenovirus virome of 55 serotypes for viruses that could kill B-cell cancers. Experimental Design: Fifteen adenoviruses selected to represent Ad species B, C, D, E, and F were tested in vitro against cell lines and primary patient B-cell cancers for their ability to infect, replicate in, and kill these cells. Select viruses were also tested against B-cell cancer xenografts in immunodeficient mice. Results: Species D adenoviruses mediated most robust killing against a range of B-cell cancer cell lines, against primary patient marginal zone lymphoma cells, and against primary patient CD138þ myeloma cells in vitro. When injected into xenografts in vivo, single treatment with select species D viruses Ad26 and Ad45 delayed lymphoma growth. Conclusions: Relatively unstudied species Dadenoviruses have a unique ability to infect and replicate in B-cell cancers as compared with other adenovirus species. These data suggest these viruses have unique biology in B cells and support translation of novel species D adenoviruses as oncolytics against B-cell cancers

Peer Reviewed Evaluation of Registered End-Points of Randomised Trials (the PRE-REPORT study): a stepped wedge, cluster-randomised trial.

OBJECTIVE: To test whether providing relevant clinical trial registry information to peer reviewers evaluating trial manuscripts decreases discrepancies between registered and published trial outcomes. DESIGN: Stepped wedge, cluster-randomised trial, with clusters comprised of eligible manuscripts submitted to each participating journal between 1 November 2018 and 31 October 2019. SETTING: Thirteen medical journals. PARTICIPANTS: Manuscripts were eligible for inclusion if they were submitted to a participating journal during the study period, presented results from the primary analysis of a clinical trial, and were peer reviewed. INTERVENTIONS: During the control phase, there were no changes to pre-existing peer review practices. After journals crossed over into the intervention phase, peer reviewers received a data sheet describing whether trials were registered, the initial registration and enrolment dates, and the registered primary outcome(s) when enrolment began. MAIN OUTCOME MEASURE: The presence of a clearly defined, prospectively registered primary outcome consistent with the primary outcome in the published trial manuscript, as determined by two independent outcome assessors. RESULTS: We included 419 manuscripts (243 control and 176 intervention). Participating journals published 43% of control-phase manuscripts and 39% of intervention-phase manuscripts (model-estimated percentage difference between intervention and control trials = -10%, 95% CI -25% to 4%). Among the 173 accepted trials, published primary outcomes were consistent with clearly defined, prospectively registered primary outcomes in 40 of 105 (38%) control-phase trials and 27 of 68 (40%) intervention-phase trials. A linear mixed model did not show evidence of a statistically significant primary outcome effect from the intervention (estimated difference between intervention and control=-6% (90% CI -27% to 15%); one-sided p value=0.68). CONCLUSIONS: These results do not support use of the tested intervention as implemented here to increase agreement between prospectively registered and published trial outcomes. Other approaches are needed to improve the quality of outcome reporting of clinical trials. TRIAL REGISTRATION NUMBER: ISRCTN41225307

MARCKS phosphorylation is modulated by a peptide mimetic of MARCKS effector domain leading to increased radiation sensitivity in lung cancer cell lines

Lung cancer is the leading cause of cancer-associated mortality in the United States. Kinase hyperactivation is a known mechanism of tumorigenesis. The phosphorylation status of the plasma membrane-associated protein myristoylated alanine rich C-kinase substrate (MARCKS) effector domain (ED) was previously established as being important in the sensitivity of lung cancer to radiation. Specifically, when MARCKS ED was in a non-phosphorylated state, lung cancer cells were more susceptible to ionizing radiation and experienced prolonged double-strand DNA breaks. Additional studies demonstrated that the phosphorylation status of MARCKS ED is important for gene expression and in vivo tumor growth. The present study used a peptide mimetic of MARCKS ED as a therapeutic intervention to modulate MARCKS phosphorylation. Culturing A549, H1792 and H1975 lung cancer cell lines with the MARCKS ED peptide led to reduced levels of phosphorylated MARCKS and phosphorylated Akt serine/threonine kinase 1. Further investigation demonstrated that the peptide therapy was able to reduce lung cancer cell proliferation and increase radiation sensitivity. In addition, the MARCKS peptide therapy was able to prolong double-strand DNA breaks following ionizing radiation exposure. The results of the present study demonstrate that a peptide mimetic of MARCKS ED is able to modulate MARCKS phosphorylation, leading to an increase in sensitivity to radiation. Keywords: lung cancer, myristoylated alanine rich C-kinase substrate, radiation sensitivity, effector domain, peptide mimeti

Human spinal cord injury causes specific increases in surface expression of beta integrins on leukocytes

Spinal cord injury (SCI) activates circulating leukocytes that migrate into the injured cord and bystander organs using adhesion molecule-mediated mechanisms. These cells cause oxidative damage, resulting in secondary injury to the spinal cord, as well as injury to bystander organs. This study was designed to examine, over a 6-h to 2-week period, changes in adhesion molecule surface expression on human peripheral leukocytes after SCI (9 subjects), using as controls 10 uninjured subjects and 6 general trauma patients (trauma controls, TC). Both the percentage of cells expressing a given adhesion molecule and the average level of its expression was quantified for both circulating neutrophils and monocytes. The percentage of neutrophils and monocytes expressing the selectin CD62L was unchanged in TC and SCI patients after injury compared to uninjured subjects. Concurrently, the amount of surface CD62L on neutrophils was decreased in SCI and TC subjects, and on monocytes after SCI. The percentage of neutrophils expressing α4 decreased in TC, but not in SCI, subjects. Likewise, the percentage of neutrophils and monocytes expressing CD11d decreased markedly in TC subjects, but not after SCI. In contrast, the mean surface expression of α4 and CD11d by neutrophils and monocytes increased after SCI compared with uninjured and TC subjects. The percentage of cells and surface expression of CD11b were similar in neutrophils of all three groups, whereas CD11b surface expression increased after SCI in monocytes. In summary, unlike changes found after general trauma, the proinflammatory stimulation induced by SCI increases the surface expression of adhesion molecules on circulating neutrophils and monocytes before they infiltrate the injured spinal cord and multiple organs of patients. Integrins may be excellent targets for anti-inflammatory treatment after human SCI. © 2011, Mary Ann Liebert, Inc