Despite considerable efforts over the past decade, only 34 fast radio bursts-intense bursts of radio emission from beyond our Galaxy-have been reported
. Attempts to understand the population as a ...whole have been hindered by the highly heterogeneous nature of the searches, which have been conducted with telescopes of different sensitivities, at a range of radio frequencies, and in environments corrupted by different levels of radio-frequency interference from human activity. Searches have been further complicated by uncertain burst positions and brightnesses-a consequence of the transient nature of the sources and the poor angular resolution of the detecting instruments. The discovery of repeating bursts from one source
, and its subsequent localization
to a dwarf galaxy at a distance of 3.7 billion light years, confirmed that the population of fast radio bursts is located at cosmological distances. However, the nature of the emission remains elusive. Here we report a well controlled, wide-field radio survey for these bursts. We found 20, none of which repeated during follow-up observations between 185-1,097 hours after the initial detections. The sample includes both the nearest and the most energetic bursts detected so far. The survey demonstrates that there is a relationship between burst dispersion and brightness and that the high-fluence bursts are the nearby analogues of the more distant events found in higher-sensitivity, narrower-field surveys
.
ABSTRACT The dust extinction curve is a critical component of many observational programs and an important diagnostic of the physics of the interstellar medium. Here we present new measurements of ...the dust extinction curve and its variation toward tens of thousands of stars, a hundred-fold larger sample than in existing detailed studies. We use data from the APOGEE spectroscopic survey in combination with ten-band photometry from Pan-STARRS1, the Two Micron All-Sky Survey, and Wide-field Infrared Survey Explorer. We find that the extinction curve in the optical through infrared is well characterized by a one-parameter family of curves described by R(V). The extinction curve is more uniform than suggested in past works, with ( R ( V ) ) = 0.18 , and with less than one percent of sight lines having R ( V ) > 4 . Our data and analysis have revealed two new aspects of Galactic extinction: first, we find significant, wide-area variations in R(V) throughout the Galactic plane. These variations are on scales much larger than individual molecular clouds, indicating that R(V) variations must trace much more than just grain growth in dense molecular environments. Indeed, we find no correlation between R(V) and dust column density up to E ( B − V ) 2 . Second, we discover a strong relationship between R(V) and the far-infrared dust emissivity.
Pulsars emit from low-frequency radio waves up to high-energy gamma-rays, generated anywhere from the stellar surface out to the edge of the magnetosphere. Detecting correlated mode changes across ...the electromagnetic spectrum is therefore key to understanding the physical relationship among the emission sites. Through simultaneous observations, we detected synchronous switching in the radio and x-ray emission properties of PSR B0943+10. When the pulsar is in a sustained radio-"bright" mode, the x-rays show only an unpulsed, nonthermal component. Conversely, when the pulsar is in a radio-"quiet" mode, the x-ray luminosity more than doubles and a 100% pulsed thermal component is observed along with the nonthermal component. This indicates rapid, global changes to the conditions in the magnetosphere, which challenge all proposed pulsar emission theories.
We explore the redshift evolution of the specific star formation rate (SSFR) for galaxies of different stellar mass by drawing on a deep 3.6 Delta *mm selected sample of >105 galaxies in the 2 deg2 ...COSMOS field. The average star formation rate (SFR) for subsets of these galaxies is estimated with stacked 1.4 GHz radio continuum emission. We separately consider the total sample and a subset of galaxies that shows evidence for substantive recent star formation in the rest-frame optical spectral energy distributions. At redshifts 0.2 < z < 3 both populations show a strong and mass-independent decrease in their SSFR toward the present epoch. It is best described by a power law (1 + z) n , where n ~ 4.3 for all galaxies and n ~ 3.5 for star-forming (SF) sources. The decrease appears to have started at z>2, at least for high-mass (M * 4 X 1010 M ) systems where our conclusions are most robust. Our data show that there is a tight correlation with power-law dependence, SSFR M * Delta *b, between SSFR and stellar mass at all epochs. The relation tends to flatten below M * 1010 M if quiescent galaxies are included; if they are excluded from the analysis a shallow index Delta *bSFG --0.4 fits the correlation. On average, higher mass objects always have lower SSFRs, also among SF galaxies. At z>1.5 there is tentative evidence for an upper threshold in SSFR that an average galaxy cannot exceed, possibly due to gravitationally limited molecular gas accretion. It is suggested by a flattening of the SSFR-M * relation (also for SF sources), but affects massive (>1010 M ) galaxies only at the highest redshifts. Since z = 1.5 there thus is no direct evidence that galaxies of higher mass experience a more rapid waning of their SSFR than lower mass SF systems. In this sense, the data rule out any strong 'downsizing' in the SSFR. We combine our results with recent measurements of the galaxy (stellar) mass function in order to determine the characteristic mass of an SF galaxy: we find that since z ~ 3 the majority of all new stars were always formed in galaxies of M * = 1010.6?0.4 M . In this sense, too, there is no 'downsizing.' Finally, our analysis constitutes the most extensive SFR density determination with a single technique out to z = 3. Recent Herschel results are consistent with our results, but rely on far smaller samples.
To assess the safety of intra-articular (IA) autologous tolerogenic dendritic cells (tolDC) in patients with inflammatory arthritis and an inflamed knee; to assess the feasibility and acceptability ...of the approach and to assess potential effects on local and systemic disease activities.
An unblinded, randomised, controlled, dose escalation Phase I trial. TolDC were differentiated from CD14+ monocytes and loaded with autologous synovial fluid as a source of autoantigens. Cohorts of three participants received 1×10
, 3×10
or 10×10
tolDC arthroscopically following saline irrigation of an inflamed (target) knee. Control participants received saline irrigation only. Primary outcome was flare of disease in the target knee within 5 days of treatment. Feasibility was assessed by successful tolDC manufacture and acceptability via patient questionnaire. Potential effects on disease activity were assessed by arthroscopic synovitis score, disease activity score (DAS)28 and Health Assessment Questionnaire (HAQ). Immunomodulatory effects were sought in peripheral blood.
There were no target knee flares within 5 days of treatment. At day 14, arthroscopic synovitis was present in all participants except for one who received 10×10
tolDC; a further participant in this cohort declined day 14 arthroscopy because symptoms had remitted; both remained stable throughout 91 days of observation. There were no trends in DAS28 or HAQ score or consistent immunomodulatory effects in peripheral blood. 9 of 10 manufactured products met quality control release criteria; acceptability of the protocol by participants was high.
IA tolDC therapy appears safe, feasible and acceptable. Knee symptoms stabilised in two patients who received 10×10
tolDC but no systemic clinical or immunomodulatory effects were detectable.
NCT01352858.
Studies of inflammatory bowel disease (IBD) have been inconclusive in relating microbiota with distribution of inflammation. We report microbiota, host transcriptomics, epigenomics and genetics from ...matched inflamed and non-inflamed colonic mucosa 50 Crohn's disease (CD); 80 ulcerative colitis (UC); 31 controls. Changes in community-wide and within-patient microbiota are linked with inflammation, but we find no evidence for a distinct microbial diagnostic signature, probably due to heterogeneous host-microbe interactions, and show only marginal microbiota associations with habitual diet. Epithelial DNA methylation improves disease classification and is associated with both inflammation and microbiota composition. Microbiota sub-groups are driven by dominant Enterbacteriaceae and Bacteroides species, representative strains of which are pro-inflammatory in vitro, are also associated with immune-related epigenetic markers. In conclusion, inflamed and non-inflamed colonic segments in both CD and UC differ in microbiota composition and epigenetic profiles.
Background
The CRTH2 antagonist OC000459 has previously been demonstrated to reduce airway inflammation and improve lung function in moderate persistent asthma. A study was conducted to determine the ...effect of lower once daily doses of OC000459 and to define the phenotype of subjects most responsive to treatment.
Methods
Adult subjects (percentage of predicted forced expiratory volume in 1 s (FEV1) 60–85%) were randomized to OC000459 at three dose levels (25 mg once daily, 200 mg once daily or 100 mg twice daily) or placebo for 12 weeks (n = 117–125 per group, full analysis set). The primary endpoint was the change from baseline in prebronchodilator FEV1, and secondary endpoints included Asthma Control Questionnaire (ACQ) and Standardised Asthma Quality of Life Questionnaire AQLQ(S), and incidence of exacerbations and respiratory tract infections.
Results
OC459 caused a significant improvement in FEV1 compared with placebo at a dose of 25 mg once daily (P = 0.028). A similar increase was observed in the other dose groups, and the mean change in FEV1 in the pooled dose groups at endpoint was 95 ml greater than placebo (P = 0.024). In a post hoc analysis of atopic eosinophilic subjects with uncontrolled asthma, a mean increase in FEV1 of 220 ml was observed compared with placebo (P = 0.005). The mean increase in FEV1 was more marked in younger subjects in this group: for subjects aged ≤40 years, there was a mean increase of 355 ml compared with placebo (P = 0.007). Improvements in ACQ and AQLQ(S) were observed in both the full analysis set and the atopic eosinophilic subgroup. There was a lower incidence of exacerbations and respiratory infections in subjects treated with OC000459. There were no drug‐related serious adverse events.
Conclusions
OC000459 is a safe and effective oral anti‐inflammatory agent, which achieved clinically meaningful improvements in lung function and asthma control in allergic asthmatics with an eosinophil‐dominant form of the disease. A dose of 25 mg given once daily was as effective as the higher doses studied.
The US Army suicide rate has increased sharply in recent years. Identifying significant predictors of Army suicides in Army and Department of Defense (DoD) administrative records might help focus ...prevention efforts and guide intervention content. Previous studies of administrative data, although documenting significant predictors, were based on limited samples and models. A career history perspective is used here to develop more textured models.
The analysis was carried out as part of the Historical Administrative Data Study (HADS) of the Army Study to Assess Risk and Resilience in Servicemembers (Army STARRS). De-identified data were combined across numerous Army and DoD administrative data systems for all Regular Army soldiers on active duty in 2004-2009. Multivariate associations of sociodemographics and Army career variables with suicide were examined in subgroups defined by time in service, rank and deployment history.
Several novel results were found that could have intervention implications. The most notable of these were significantly elevated suicide rates (69.6-80.0 suicides per 100 000 person-years compared with 18.5 suicides per 100 000 person-years in the total Army) among enlisted soldiers deployed either during their first year of service or with less than expected (based on time in service) junior enlisted rank; a substantially greater rise in suicide among women than men during deployment; and a protective effect of marriage against suicide only during deployment.
A career history approach produces several actionable insights missed in less textured analyses of administrative data predictors. Expansion of analyses to a richer set of predictors might help refine understanding of intervention implications.
Behavioural syndromes are correlations between behaviours in different functional contexts. Behavioural syndromes are attracting the attention of evolutionary biologists because they mean that ...different behaviours might not be free to evolve independently of one another. In a landmark study, Huntingford (1976) showed that individual stickleback which were bold toward predators were also aggressive toward conspecifics and active in an unfamiliar environment. Here, I revisited the activity‐aggression‐boldness syndrome in stickleback and tested the hypothesis that correlations between behaviours might act as evolutionary constraints. I measured a suite of behaviours on wild‐caught individuals and their offspring from two different populations and calculated heritabilities and genetic correlations between the different behaviours. I found that these behaviours were phenotypically and genetically correlated in one population but not another. On average, boldness and aggression were negatively related to each other across the populations. These results suggest that behavioural syndromes don't always act as evolutionary constraints.
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