Lessons from helminth infections: ES-62 highlights new interventional approaches in rheumatoid arthritis

Parasitic worms are able to survive in their mammalian host for many years due to their ability to manipulate the immune response by secreting immunomodulatory products. It is increasingly clear that, reflecting the anti-inflammatory actions of such worm-derived immunomodulators, there is an inverse correlation between helminth infection and autoimmune diseases in the developing world. As the decrease in helminth infections due to increased sanitation has correlated with an alarming increase in prevalence of such disorders in industrialised countries, this "Hygiene Hypothesis" has led to the proposal that worms and their secreted products offer a novel platform for the development of safe and effective strategies for the treatment of autoimmune disorders. Here we review the anti-inflammatory effects of one such immunomodulator, ES-62 on innate and adaptive immune responses and the mechanisms it exploits to afford protection in the murine Collagen Induced Arthritis (CIA) model of rheumatoid arthritis (RA). As its core mechanism involves targeting of IL-17 responses, which despite being pathogenic in RA are important for combating infection, we discuss how its selective targeting of IL-17 production by Th17 and γδ T cells, whilst leaving that of CD49b+ Natural Killer (NK and NK T) cells intact, reflects the ability of helminths to modulate the immune system without immunocompromising the host. Exploiting helminth immunomodulatory mechanisms therefore offers the potential for safer therapies than current biologics, such as "IL-17 blockers", that are not able to discriminate sources of IL-17 and hence present adverse effects that limit their therapeutic potential

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

Diffuse Gas and LMXBs in the Chandra Observation of the S0 Galaxy NGC 1553

We have spatially and spectrally resolved the sources of X-ray emission from the X-ray faint S0 galaxy NGC 1553 using an observation from the Chandra X-ray Observatory. The majority (70%) of the emission in the 0.3 - 10.0 keV band is diffuse, and the remaining 30% is resolved into 49 discrete sources. Most of the discrete sources associated with the galaxy appear to be low mass X-ray binaries (LMXBs). The luminosity function of the LMXB sources is well-fit by a broken power-law with a break luminosity comparable to the Eddington luminosity for a 1.4 solar mass neutron star. It is likely that those sources with luminosities above the break are accreting black holes and those below are mostly neutron stars in binary systems. Spectra were extracted for the total emission, diffuse emission, and sum of the resolved sources; the spectral fits for all require a model including both a soft and hard component. The diffuse emission is predominately soft while the emission from the sources is mostly hard. Approximately 24% of the diffuse emission arises from unresolved LMXBs, with the remainder resulting from thermal emission from hot gas. There is a very bright source at the projected position of the nucleus of the galaxy. The spectrum and luminosity derived from this central source are consistent with it being an AGN; the galaxy also is a weak radio source. Finally, the diffuse emission exhibits significant substructure with an intriguing spiral feature passing through the center of the galaxy. The X-ray spectrum and surface brightness of the spiral feature are consistent with adiabatic or shock compression of ambient gas, but not with cooling. This feature may be due to compression of the hot interstellar gas by radio lobes or jets associated with the AGN.Comment: 23 pages using emulateapj.sty; ApJ, in press; revised version includes correction to error in the L_X,src/L_B ratio as well as other revision

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

Radio Continuum Jet in NGC 7479

The barred galaxy NGC 7479 hosts a remarkable jet-like radio continuum feature: bright, 12-kpc long in projection, and hosting an aligned magnetic field. The degree of polarization is 6%-8% along the jet, and remarkably constant, which is consistent with helical field models. The radio brightness of the jet suggests strong interaction with the ISM and hence a location near the disk plane. We observed NGC 7479 at four wavelengths with the VLA and Effelsberg radio telescopes. The equipartition strength is 35-40 micro-G for the total and >10 micro-G for the ordered magnetic field in the jet. The jet acts as a bright, polarized background. Faraday rotation between 3.5 and 6 cm and depolarization between 6 and 22 cm can be explained by magneto-ionic gas in front of the jet, with thermal electron densities of ~0.06 cm**(-3) in the bar and ~0.03 cm**(-3) outside the bar. The regular magnetic field along the bar points toward the nucleus on both sides. The regular field in the disk reveals multiple reversals, probably consisting of field loops stretched by a shearing gas flow in the bar. The projection of the jet bending in the sky plane is in the sense opposite to that of the underlying stellar and gaseous spiral structure. The bending in 3-D is most easily explained as a precessing jet, with an age less than 10**6 years. Our observations are consistent with very recent triggering, possibly by a minor merger. NGC 7479 provides a unique opportunity to study interaction-triggered 15-kpc scale radio jets within a spiral galaxy.Comment: 18 pages, 21 figures, accepted for publication in the Astrophysical Journa

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

Linearized gravity and gauge conditions

In this paper we consider the field equations for linearized gravity and other integer spin fields on the Kerr spacetime, and more generally on spacetimes of Petrov type D. We give a derivation, using the GHP formalism, of decoupled field equations for the linearized Weyl scalars for all spin weights and identify the gauge source functions occuring in these. For the spin weight 0 Weyl scalar, imposing a generalized harmonic coordinate gauge yields a generalization of the Regge-Wheeler equation. Specializing to the Schwarzschild case, we derive the gauge invariant Regge-Wheeler and Zerilli equation directly from the equation for the spin 0 scalar.Comment: 24 pages, corresponds to published versio

Towards an Understanding of the Mid-Infrared Surface Brightness of Normal Galaxies

We report a mid-infrared color and surface brightness analysis of IC 10, NGC 1313, and NGC 6946, three of the nearby galaxies studied under the Infrared Space Observatory Key Project on Normal Galaxies. Images with < 9 arcsecond (170 pc) resolution of these nearly face-on, late-type galaxies were obtained using the LW2 (6.75 mu) and LW3 (15 mu) ISOCAM filters. Though their global I_nu(6.75 mu)/I_nu(15 mu) flux ratios are similar and typical of normal galaxies, they show distinct trends of this color ratio with mid-infrared surface brightness. We find that I_nu(6.75 mu)/I_nu(15 mu) ~< 1 only occurs for regions of intense heating activity where the continuum rises at 15 micron and where PAH destruction can play an important role. The shape of the color-surface brightness trend also appears to depend, to the second-order, on the hardness of the ionizing radiation. We discuss these findings in the context of a two-component model for the phases of the interstellar medium and suggest that star formation intensity is largely responsible for the mid-infrared surface brightness and colors within normal galaxies, whereas differences in dust column density are the primary drivers of variations in the mid-infrared surface brightness between the disks of normal galaxies.Comment: 19 pages, 6 figures, uses AAS LaTeX; to appear in the November Astronomical Journa

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

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