Reducing LPS content in cockroach allergens increases pulmonary cytokine production without increasing inflammation: A randomized laboratory study

<p>Abstract</p> <p>Background</p> <p>Endotoxins are ubiquitously present in the environment and constitute a significant component of ambient air. These substances have been shown to modulate the allergic response, however a consensus has yet to be reached whether they attenuate or exacerbate asthmatic responses. The current investigation examined whether reducing the concentration of lipopolysaccharide (LPS) in a house dust extract (HDE) containing high concentrations of both cockroach allergens <abbrgrp><abbr bid="B1">1</abbr></abbrgrp> and LPS would attenuate asthma-like pulmonary inflammation.</p> <p>Methods</p> <p>Mice were sensitized with CRA and challenged with the intact HDE, containing 182 ng of LPS, or an LPS-reduced HDE containing 3 ng LPS, but an equivalent amount of CRA. Multiple parameters of asthma-like pulmonary inflammation were measured.</p> <p>Results</p> <p>Compared to HDE challenged mice, the LPS-reduced HDE challenged mice had significantly reduced TNFα levels in the bronchoalveolar lavage fluid. Plasma levels of IgE and IgG1 were significantly reduced, however no change in CRA-specific IgE was detected. In HDE mice, plasma IgG2a levels were similar to naïve mice, while LPS-reduced HDE mice had significantly greater concentrations. Reduced levels of LPS in the HDE did not decrease eosinophil or neutrophil recruitment into the alveolar space. Equivalent inflammatory cell recruitment occurred despite having generally higher pulmonary concentrations of eotaxins and CXC chemokines in the LPS-reduced HDE group. LPS-reduced HDE challenge induced significantly higher concentrations of IFNγ, and IL-5 and IL-13 in the BAL fluid, but did not decrease airways hyperresponsiveness or airway resistance to methacholine challenge. <it>Conclusion: </it>These data show that reduction of LPS levels in the HDE does not significantly protect against the severity of asthma-like pulmonary inflammation.</p

Low-Frequency Observations of the Moon with the Murchison Widefield Array

A new generation of low-frequency radio telescopes is seeking to observe the redshifted 21 cm signal from the epoch of reionization (EoR), requiring innovative methods of calibration and imaging to overcome the difficulties of wide-field low-frequency radio interferometry. Precise calibration will be required to separate the expected small EoR signal from the strong foreground emission at the frequencies of interest between 80 and 300 MHz. The Moon may be useful as a calibration source for detection of the EoR signature, as it should have a smooth and predictable thermal spectrum across the frequency band of interest. Initial observations of the Moon with the Murchison Widefield Array 32 tile prototype show that the Moon does exhibit a similar trend to that expected for a cool thermally emitting body in the observed frequency range, but that the spectrum is corrupted by reflected radio emission from Earth. In particular, there is an abrupt increase in the observed flux density of the Moon within the internationally recognized frequency modulated (FM) radio band. The observations have implications for future low-frequency surveys and EoR detection experiments that will need to take this reflected emission from the Moon into account. The results also allow us to estimate the equivalent isotropic power emitted by the Earth in the FM band and to determine how bright the Earth might appear at meter wavelengths to an observer beyond our own solar system

Low frequency observations of linearly polarized structures in the interstellar medium near the south Galactic pole

This is an author-created, un-copyedited version of an article published in The Astrophysical Journal. IOP Publishing Ltd is not responsible for any errors or omissions in this version of the manuscript or any version derived from it. The Version of Record is available online at https://doi.org/10.3847/0004-637X/830/1/38We present deep polarimetric observations at 154 MHz with the Murchison Widefield Array (MWA), covering 625 deg^2 centered on RA=0 h, Dec=-27 deg. The sensitivity available in our deep observations allows an in-band, frequency-dependent analysis of polarized structure for the first time at long wavelengths. Our analysis suggests that the polarized structures are dominated by intrinsic emission but may also have a foreground Faraday screen component. At these wavelengths, the compactness of the MWA baseline distribution provides excellent snapshot sensitivity to large-scale structure. The observations are sensitive to diffuse polarized emission at ~54' resolution with a sensitivity of 5.9 mJy beam^-1 and compact polarized sources at ~2.4' resolution with a sensitivity of 2.3 mJy beam^-1 for a subset (400 deg^2) of this field. The sensitivity allows the effect of ionospheric Faraday rotation to be spatially and temporally measured directly from the diffuse polarized background. Our observations reveal large-scale structures (~1 deg - 8 deg in extent) in linear polarization clearly detectable in ~2 minute snapshots, which would remain undetectable by interferometers with minimum baseline lengths >110 m at 154 MHz. The brightness temperature of these structures is on average 4 K in polarized intensity, peaking at 11 K. Rotation measure synthesis reveals that the structures have Faraday depths ranging from -2 rad m^-2 to 10 rad m^-2 with a large fraction peaking at ~+1 rad m^-2. We estimate a distance of 51+/-20 pc to the polarized emission based on measurements of the in-field pulsar J2330-2005. We detect four extragalactic linearly polarized point sources within the field in our compact source survey. Based on the known polarized source population at 1.4 GHz and non-detections at 154 MHz, we estimate an upper limit on the depolarization ratio of 0.08 from 1.4 GHz to 154 MHz.Peer reviewedFinal Accepted Versio

The Beaker phenomenon and the genomic transformation of northwest Europe

From around 2750 to 2500 bc, Bell Beaker pottery became widespread across western and central Europe, before it disappeared between 2200 and 1800 bc. The forces that propelled its expansion are a matter of long-standing debate, and there is support for both cultural diffusion and migration having a role in this process. Here we present genome-wide data from 400 Neolithic, Copper Age and Bronze Age Europeans, including 226 individuals associated with Beaker-complex artefacts. We detected limited genetic affinity between Beaker-complex-associated individuals from Iberia and central Europe, and thus exclude migration as an important mechanism of spread between these two regions. However, migration had a key role in the further dissemination of the Beaker complex. We document this phenomenon most clearly in Britain, where the spread of the Beaker complex introduced high levels of steppe-related ancestry and was associated with the replacement of approximately 90% of Britain’s gene pool within a few hundred years, continuing the east-to-west expansion that had brought steppe-related ancestry into central and northern Europe over the previous centuries

Effects of Anacetrapib in Patients with Atherosclerotic Vascular Disease

BACKGROUND: Patients with atherosclerotic vascular disease remain at high risk for cardiovascular events despite effective statin-based treatment of low-density lipoprotein (LDL) cholesterol levels. The inhibition of cholesteryl ester transfer protein (CETP) by anacetrapib reduces LDL cholesterol levels and increases high-density lipoprotein (HDL) cholesterol levels. However, trials of other CETP inhibitors have shown neutral or adverse effects on cardiovascular outcomes. METHODS: We conducted a randomized, double-blind, placebo-controlled trial involving 30,449 adults with atherosclerotic vascular disease who were receiving intensive atorvastatin therapy and who had a mean LDL cholesterol level of 61 mg per deciliter (1.58 mmol per liter), a mean non-HDL cholesterol level of 92 mg per deciliter (2.38 mmol per liter), and a mean HDL cholesterol level of 40 mg per deciliter (1.03 mmol per liter). The patients were assigned to receive either 100 mg of anacetrapib once daily (15,225 patients) or matching placebo (15,224 patients). The primary outcome was the first major coronary event, a composite of coronary death, myocardial infarction, or coronary revascularization. RESULTS: During the median follow-up period of 4.1 years, the primary outcome occurred in significantly fewer patients in the anacetrapib group than in the placebo group (1640 of 15,225 patients [10.8%] vs. 1803 of 15,224 patients [11.8%]; rate ratio, 0.91; 95% confidence interval, 0.85 to 0.97; P=0.004). The relative difference in risk was similar across multiple prespecified subgroups. At the trial midpoint, the mean level of HDL cholesterol was higher by 43 mg per deciliter (1.12 mmol per liter) in the anacetrapib group than in the placebo group (a relative difference of 104%), and the mean level of non-HDL cholesterol was lower by 17 mg per deciliter (0.44 mmol per liter), a relative difference of -18%. There were no significant between-group differences in the risk of death, cancer, or other serious adverse events. CONCLUSIONS: Among patients with atherosclerotic vascular disease who were receiving intensive statin therapy, the use of anacetrapib resulted in a lower incidence of major coronary events than the use of placebo. (Funded by Merck and others; Current Controlled Trials number, ISRCTN48678192 ; ClinicalTrials.gov number, NCT01252953 ; and EudraCT number, 2010-023467-18 .)

A Conversion-Period Cemetery at Woodlands, Adwick-le-Street, South Yorkshire*

Excavations by Archaeological Research and Consultancy University of Sheffield in 2007–8 revealed the remains of an Anglo-Saxon inhumation cemetery at North Ridge Community School, Woodlands, Doncaster. Forty graves were excavated, thirty-seven of which contained in situ burial remains. Radiocarbon samples from five graves gave an overall date range extending from the late seventh to late eight centuries AD. The latter is commensurate with that suggested by the limited range of grave goods recovered from two of the graves. The majority of the burials were made supine and extended within graves predominantly arranged in two rows, and the demographic profile suggests it served a domestic population. There were occasional deviations from the ‘norm’ in burial position and orientation, and one adult female appears to have suffered a violent death. Strontium and Oxygen (Sr/O) isotope analysis of seven individuals showed mixed origins including local, regional/national migrants and two long-distance migrants

Results of an archaeological watching brief on land adjacent to Warnford Road, Corhampton, Hampshire

An archaeological watching brief undertaken during the redevelopment of land adjacent to Warnford Road, Corhampton, Hampshire revealed Early Holocene stratigraphic sequences including a palaeosol within which molluscs and pollen were preserved. A radiocarbon date of 9160–8790 cal BC was obtained on charcoal from the palaeosol. A Middle Iron Age ditch into which an apparently in situ inhumation burial, radiocarbon dated to 400–230 cal BC, had been placed at its base, was also found

Tango through different eyes. Adapting tango classes for seniors with visual impairment

Un projet de recherche multidisciplinaire a été réalisé en 2010 dans le but de vérifier s'il était faisable de développer un cours de tango argentin adapté aux personnes âgées ayant une déficience visuelle, et d'évaluer son impact sur leur bien-être physique et psychologique. Le présent document y fait suite. Il offre des éléments pouvant guider les réflexions et les démarches des intervenants ou des organisations qui désireraient adapter un cours de tango argentin afin d'y intégrer des personnes âgées ayant une déficience visuelle. L'on y présente, entre autres, différents types d'adaptations pouvant faciliter leur intégration, des recommandations visant à faciliter l'implantation d'un cours de tango adapté dans la communauté ainsi que le point de vue des participants et des partenaires de danse

A Romano-British enclosure near Rossington, South Yorkshire

Excavations in 2012 and 2014 examined a small sub-square enclosure, associated field system and four adjacent waterholes. A patch of cremated human bone radiocarbon dated to the early–mid-Romano-British period was revealed in the partially silted enclosure ditch; the small quantity of bone recovered may suggest that it was a secondary deposit. A small assemblage of finds including Romano-British pottery was collected. The wider landscape setting of the site is examined