The Discovery of a Giant H-alpha Filament in NGC 7213

The nearby Seyfert galaxy NGC 7213 has been imaged in H-alpha and HI with the CTIO 1.5 m telescope and with the Australia Telescope Compact Array (ATCA), respectively. Optically NGC 7213 looks undisturbed and relatively featureless but the continuum-subtracted H-alpha image shows a 19 kpc long filament located approximately 18.6 kpc from the nucleus. The H-alpha filament could be neutral gas photo-ionized by the active nucleus, as has been suggested for the Seyfert galaxy NGC 5252, or shock-ionized by a jet interacting with the surrounding HI, as has been suggested for the radio galaxy PKS 2240-41. The HI map reveals NGC 7213 to be a highly disturbed system suggesting a past merging event.Comment: 14 pages including 4 figures and 1 table. Figures 1-4 are in jpeg format; Better quality images can be retrieved in postscript format at ftp://charon.nmsu.edu/pub/shameed/ ; Accepted for publication in ApJ Letter

Large-Scale CO Maps of the Lupus Molecular Cloud Complex

Fully sampled degree-scale maps of the 13CO 2-1 and CO 4-3 transitions toward three members of the Lupus Molecular Cloud Complex - Lupus I, III, and IV - trace the column density and temperature of the molecular gas. Comparison with IR extinction maps from the c2d project requires most of the gas to have a temperature of 8-10 K. Estimates of the cloud mass from 13CO emission are roughly consistent with most previous estimates, while the line widths are higher, around 2 km/s. CO 4-3 emission is found throughout Lupus I, indicating widespread dense gas, and toward Lupus III and IV. Enhanced line widths at the NW end and along the edge of the B228 ridge in Lupus I, and a coherent velocity gradient across the ridge, are consistent with interaction between the molecular cloud and an expanding HI shell from the Upper-Scorpius subgroup of the Sco-Cen OB Association. Lupus III is dominated by the effects of two HAe/Be stars, and shows no sign of external influence. Slightly warmer gas around the core of Lupus IV and a low line width suggest heating by the Upper-Centaurus-Lupus subgroup of Sco-Cen, without the effects of an HI shell.Comment: 54 pages, 27 figures, 5 tables. To appear in ApJS. Preprint also available (with full-size figures) from http://www.astro.ex.ac.uk/people/nfht/publications.html Datacubes available from http://www.astro.ex.ac.uk/people/nfht/resources.htm

The helminth product, ES-62, protects against airway inflammation by resetting the Th cell phenotype

We previously demonstrated inhibition of ovalbumin (OVA)-induced allergic airway hyper-responsiveness in the mouse using ES-62, a phosphorylcholine-containing glycoprotein secreted by the filarial nematode, Acanthocheilonema viteae. This inhibition correlated with ES-62-induced mast cell desensitisation, although the degree to which this reflected direct targeting of mast cells remained unclear as suppression of the Th2 phenotype of the inflammatory response, as measured by eosinophilia and IL-4 levels in the lungs, was also observed. We now show that inhibition of the lung Th2 phenotype is reflected in ex vivo analyses of draining lymph node recall cultures and accompanied by a decrease in the serum levels of total and OVA-specific IgE. Moreover, ES-62 also suppresses the lung infiltration by neutrophils that is associated with severe asthma and is generally refractory to conventional anti-inflammatory therapies, including steroids. Protection against Th2-associated airway inflammation does not reflect induction of regulatory T cell (Treg) responses (there is no increased IL-10 or Foxp3 expression) but rather a switch in polarisation towards increased T-bet expression and IFNγ production. This ES-62-driven switch in the Th1/Th2 balance is accompanied by decreased IL-17 responses, a finding in line with reports that IFNγ and IL-17 are counter-regulatory. Consistent with ES-62 mediating its effects via IFNγ-mediated suppression of pathogenic Th2/Th17 responses, we found that neutralising anti-IFNγ antibodies blocked protection against airway inflammation in terms of pro-inflammatory cell infiltration, particularly by neutrophils and lung pathology. Collectively, these studies indicate that ES-62, or more likely small molecule analogues, could have therapeutic potential in asthma, in particular for those subtypes of patients (e.g. smokers, steroid-resistant) who are refractory to current treatments

The carbohydrate-linked phosphorylcholine of the parasitic nematode product ES-62 modulates complement activation

Parasitic nematodes manufacture various carbohydratelinked phosphorylcholine (PCh)-containing molecules, including ES-62, a protein with an N-linked glycan terminally substituted with PCh. The PCh component is biologically important because it is required for immunomodulatory effects. We showed that most ES-62 was bound to a single protein, C-reactive protein (CRP), in normal human serum, displaying a calcium-dependent, high-avidity interaction and ability to form large complexes. Unexpectedly, CRP binding to ES-62 failed to efficiently activate complement as far as the C3 convertase stage in comparison with PCh-BSA and PCh-containing Streptococcus pneumoniae cell wall polysaccharide. C1q capture assays demonstrated an ES-62-CRP-C1q interaction in serum. The three ligands all activated C1 and generated C4b to similar extents. However, a C2a active site was not generated following ES-62 binding to CRP, demonstrating that C2 cleavage was far less efficient for ES-62-containing complexes. We proposed that failure of C2 cleavage was due to the flexible nature of carbohydrate-bound PCh and that reduced proximity of the C1 complex was the reason that C2 was poorly cleaved. This was confirmed using synthetic analogues that were similar to ES-62 only in respect of having a flexible PCh. Furthermore, ES-62 was shown to deplete early complement components, such as the rate-limiting C4, following CRP interaction and thereby inhibit classical pathway activation. Thus, flexible PCh-glycan represents a novel mechanism for subversion of complement activation. These data illustrate the importance of the rate-limiting C4/C2 stage of complement activation and reveal a new addition to the repertoire of ES-62 immunomodulatory mechanisms with possible therapeutic applications

Hard X-ray Luminosities of Multinuclei Infrared Luminous Galaxies Showing a Radio/Far-Infrared Excess

We report the results of hard X-ray observations of four multinuclei merging infrared luminous galaxies (IRLGs). We selected these four sources for their excess of radio to far-infrared luminosity ratio compared with starburst galaxies. This excess suggests that activity associated with a supermassive black hole (SMBH) contributes strongly to the IRLGs' bolometric luminosities. Although we expect strong hard X-ray emission from the SMBH-driven activity, the radio-excess multinuclei merging IRLGs show considerably smaller hard X-ray luminosities relative to far-infrared (40$-$500 $\mu$m) and infrared (8$-$1000 $\mu$m) luminosities than active galactic nuclei (AGNs) showing a similar radio-excess. This result may demonstrate that emission in the hard X-ray region from SMBH-driven activity in the multinuclei merging IRLGs is severely suppressed compared to a typical spectral energy distribution of SMBH-driven activity in AGNs. If this is a common property of merging IRLGs, without its correction, hard X-ray observations underestimate the contribution of SMBH-driven activity to the bolometric luminosities of merging IRLGs.Comment: 25 pages of text, 4 figures, aaspp4.sty, Astrophysical Journal, in press (1999, Volume 527

It\u27s about the patients: Practical antibiotic stewardship in outpatient settings in the United States

Antibiotic-resistant pathogens cause over 35,000 preventable deaths in the United States every year, and multiple strategies could decrease morbidity and mortality. As antibiotic stewardship requirements are being deployed for the outpatient setting, community providers are facing systematic challenges in implementing stewardship programs. Given that the vast majority of antibiotics are prescribed in the outpatient setting, there are endless opportunities to make a smart and informed choice when prescribing and to move the needle on antibiotic stewardship. Antibiotic stewardship in the community, or smart prescribing as we suggest, should factor in antibiotic efficacy, safety, local resistance rates, and overall cost, in addition to patient-specific factors and disease presentation, to arrive at an appropriate therapy. Here, we discuss some of the challenges, such as patient/parent pressure to prescribe, lack of data or resources for implementation, and a disconnect between guidelines and real-world practice, among others. We have assembled an easy-to-use best practice guide for providers in the outpatient setting who lack the time or resources to develop a plan or consult lengthy guidelines. We provide specific suggestions for antibiotic prescribing that align real-world clinical practice with best practices for antibiotic stewardship for two of the most common bacterial infections seen in the outpatient setting: community-acquired pneumonia and skin and soft-tissue infection. In addition, we discuss many ways that community providers, payors, and regulatory bodies can make antibiotic stewardship easier to implement and more streamlined in the outpatient setting

Follow-up of blood-pressure lowering and glucose control in type 2 diabetes.

BACKGROUND In the Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation (ADVANCE) factorial trial, the combination of perindopril and indapamide reduced mortality among patients with type 2 diabetes, but intensive glucose control, targeting a glycated hemoglobin level of less than 6.5%, did not. We now report results of the 6-year post-trial follow-up. METHODS We invited surviving participants, who had previously been assigned to perindopril–indapamide or placebo and to intensive or standard glucose control (with the glucose-control comparison extending for an additional 6 months), to participate in a post-trial follow-up evaluation. The primary end points were death from any cause and major macrovascular events. RESULTS The baseline characteristics were similar among the 11,140 patients who originally underwent randomization and the 8494 patients who participated in the post-trial follow-up for a median of 5.9 years (blood-pressure–lowering comparison) or 5.4 years (glucose-control comparison). Between-group differences in blood pressure and glycated hemoglobin levels during the trial were no longer evident by the first post-trial visit. The reductions in the risk of death from any cause and of death from cardiovascular causes that had been observed in the group receiving active blood-pressure–lowering treatment during the trial were attenuated but significant at the end of the post-trial follow-up; the hazard ratios were 0.91 (95% confidence interval [CI], 0.84 to 0.99; P=0.03) and 0.88 (95% CI, 0.77 to 0.99; P=0.04), respectively. No differences were observed during follow-up in the risk of death from any cause or major macrovascular events between the intensive-glucose-control group and the standard-glucose-control group; the hazard ratios were 1.00 (95% CI, 0.92 to 1.08) and 1.00 (95% CI, 0.92 to 1.08), respectively. CONCLUSIONS The benefits with respect to mortality that had been observed among patients originally assigned to blood-pressure–lowering therapy were attenuated but still evident at the end of follow-up. There was no evidence that intensive glucose control during the trial led to long-term benefits with respect to mortality or macrovascular events