Summary Background Existing treatments for postherpetic neuralgia, and for neuropathic pain in general, are limited by modest efficacy and unfavourable side-effects. The angiotensin II type 2 ...receptor (AT2 R) is a new target for neuropathic pain. EMA401, a highly selective AT2 R antagonist, is under development as a novel neuropathic pain therapeutic agent. We assessed the therapeutic potential of EMA401 in patients with postherpetic neuralgia. Methods In this multicentre, placebo-controlled, double-blind, randomised, phase 2 clinical trial, we enrolled patients (aged 22–89 years) with postherpetic neuralgia of at least 6 months' duration from 29 centres across six countries. We randomly allocated 183 participants to receive either oral EMA401 (100 mg twice daily) or placebo for 28 days. Randomisation was done according to a centralised randomisation schedule, blocked by study site, which was generated by an independent, unmasked statistician. Patients and staff at each site were masked to treatment assignment. We assessed the efficacy, safety, and pharmacokinetics of EMA401. The primary efficacy endpoint was change in mean pain intensity between baseline and the last week of dosing (days 22–28), measured on an 11-point numerical rating scale. The primary efficacy analysis was intention to treat. This trial is registered with the Australian New Zealand Clinical Trials Registry, number ACTRN12611000822987. Findings 92 patients were assigned to EMA401 and 91 were assigned to placebo. The patients given EMA401 reported significantly less pain compared with baseline values in the final week of treatment than did those given placebo (mean reductions in pain scores −2·29 SD 1·75 vs −1·60 1·66; difference of adjusted least square means −0·69 SE 0·25; 95% CI −1·19 to −0·20; p=0·0066). No serious adverse events related to EMA401 occurred. Overall, 32 patients reported 56 treatment-emergent adverse events in the EMA401 group compared with 45 such events reported by 29 patients given placebo. Interpretation EMA401 (100 mg twice daily) provides superior relief of postherpetic neuralgia compared with placebo at the end of 28 days of treatment. EMA401 was well tolerated by patients. Funding Spinifex Pharmaceuticals.
Swine dysentery is causally associated with
Brachyspira hampsonii
and
B
.
hyodysenteriae
infection. Given the importance of transmission models in understanding re-emergent diseases and developing ...control strategies such as vaccines, the objective of this experiment was to evaluate two experimental natural transmission (seeder pig) models in grower pigs, each with 24 animals. Seeder pigs were intragastrically inoculated using broth cultures of either
B
.
hampsonii
strain 30446 (genomovar II) or
B
.
hyodysenteriae
strain G44. In trial 1, three seeder pigs were placed into two pens containing nine susceptible contact pigs creating a 1:3 seeder:contact ratio. This was sufficient to achieve natural
B
.
hampsonii
infection of 13/18 (72%) contact pigs, however, the incidence of mucoid or mucohemorrhagic diarrhea (MMHD) in contact pigs differed significantly between pens (4/9 versus 9/9;
P
= 0.03). In trial 2, eight seeder pigs inoculated intragastrically with
B
.
hampsonii
did not develop MMHD but when re-inoculated with
B
.
hyodysenteriae
14 days later, all developed mucohemorrhagic diarrhea within 13 days of re-inoculation. Two seeder pigs were placed into each of 4 contact pens each containing 4 pigs. This 1:2 seeder:contact ratio resulted in natural infection of 14/16 (87%) contact pigs with incubation period ranging from 9–15 days. There were no significant differences among pens in incubation period, duration, clinical period or severity of diarrhea. These trials demonstrated that a 1:2 seeder:contact ratio with groups of six grower pigs per pen sustained natural transmission of
B
.
hyodysenteriae
G44 with greater consistency in the incidence of MMHD among pens compared to a
B
.
hampsonii
30446 transmission model using 1:3 seeder:contact ratio in pens of 12. Understanding why
B
.
hampsonii
intragastric inoculation failed in one experiment warrants additional research.
The stellar initial mass function (IMF) describes the distribution in stellar masses produced from a burst of star formation. For more than 50 yr, the implicit assumption underpinning most areas of ...research involving the IMF has been that it is universal, regardless of time and environment. We measure the high-mass IMF slope for a sample of low-to-moderate redshift galaxies from the Galaxy and Mass Assembly survey. The large range in luminosities and galaxy masses of the sample permits the exploration of underlying IMF dependencies. A strong IMF-star formation rate dependency is discovered, which shows that highly star-forming galaxies form proportionally more massive stars (they have IMFs with flatter power-law slopes) than galaxies with low star formation rates. This has a significant impact on a wide variety of galaxy evolution studies, all of which rely on assumptions about the slope of the IMF. Our result is supported by, and provides an explanation for, the results of numerous recent explorations suggesting a variation of or evolution in the IMF.
Galaxy and Mass Assembly (GAMA) is a project to study galaxy formation and evolution, combining imaging data from ultraviolet to radio with spectroscopic data from the AAOmega spectrograph on the ...Anglo-Australian Telescope. Using data from Phase 1 of GAMA, taken over three observing seasons, and correcting for various minor sources of incompleteness, we calculate galaxy luminosity functions (LFs) and their evolution in the ugriz passbands.
At low redshift, z < 0.1, we find that blue galaxies, defined according to a magnitude-dependent but non-evolving colour cut, are reasonably well fitted over a range of more than 10 magnitudes by simple Schechter functions in all bands. Red galaxies, and the combined blue plus red sample, require double power-law Schechter functions to fit a dip in their LF faintwards of the characteristic magnitude M* before a steepening faint end. This upturn is at least partly due to dust-reddened disc galaxies.
We measure the evolution of the galaxy LF over the redshift range 0.002 < z < 0.5 both by using a parametric fit and by measuring binned LFs in redshift slices. The characteristic luminosity L* is found to increase with redshift in all bands, with red galaxies showing stronger luminosity evolution than blue galaxies. The comoving number density of blue galaxies increases with redshift, while that of red galaxies decreases, consistent with prevailing movement from blue cloud to red sequence. As well as being more numerous at higher redshift, blue galaxies also dominate the overall luminosity density beyond redshifts z≃ 0.2. At lower redshifts, the luminosity density is dominated by red galaxies in the riz bands, and by blue galaxies in u and g.
Abstract
We present the average rest-frame spectrum of the final catalog of dusty star-forming galaxies (DSFGs) selected from the South Pole Telescope's SPT-SZ survey and measured with Band 3 of the ...Atacama Large Millimeter/submillimeter Array. This work builds on the previous average rest-frame spectrum, given in Spilker et al. (2014) for the first 22 sources, and is comprised of a total of 78 sources, normalized by their respective apparent dust masses. The spectrum spans 1.9 <
z
< 6.9 and covers rest-frame frequencies of 240–800 GHz. Combining this data with low-
J
CO observations from the Australia Telescope Compact Array, we detect multiple bright line features from
12
CO, C
i
, and H
2
O, as well as fainter molecular transitions from
13
CO, HCN, HCO
+
, HNC, CN, H
2
O
+
, and CH. We use these detections, along with limits from other molecules, to characterize the typical properties of the interstellar medium (ISM) for these high-redshift DSFGs. We are able to divide the large sample into subsets in order to explore how the average spectrum changes with various galaxy properties, such as effective dust temperature. We find that systems with hotter dust temperatures exhibit differences in the bright
12
CO emission lines, and contain either warmer and more excited dense gas tracers or larger dense gas reservoirs. These observations will serve as a reference point to studies of the ISM in distant luminous DSFGs (
L
IR
> 10
12
L
⊙
), and will inform studies of chemical evolution before the peak epoch of star formation at
z
= 2–3.
Swine dysentery (SD) caused by pathogenic Brachyspira spp. is an economic challenge for the swine industry. In research settings, experimental reproduction of swine dysentery typically relies on ...intragastric inoculation which has shown variable success. This project aimed to improve the consistency of the experimental inoculation protocol used for swine dysentery in our laboratory. Over six experiments, we evaluated the influence of group housing in inoculated pigs using a frozen-thawed broth culture of strongly hemolytic B. hyodysenteriae strain D19 (Trial A), compared the relative virulence of B. hyodysenteriae strains D19 and G44 (Trial B), compared inoculum volumes (50 mL vs 100 mL) for G44 and B. hampsonii 30446 (Trial C), and performed three independent trials evaluating intragastric inoculation using different oral inoculation methods: oral feed balls (Trial D), and oral syringe bolus of 100 mL (Trial E) or 300 mL (Trial F). Intragastric inoculation with a fresh broth culture of B. hyodysenteriae strain G44 resulted in a shorter incubation period and a higher proportionate duration of mucohemorrhagic diarrhea (MMHD) compared to D19. Intragastric inoculation with either 50 or 100 mL of B. hampsonii 30446 or B. hyodysenteriae (G44) were statistically equivalent. Oral inoculation with 100 mL or 300 mL also yielded similar results to intragastric inoculation but was more expensive due to the additional work and supplies associated with syringe training. Our future research will use intragastric inoculation with 100 mL of a fresh broth culture containing B. hyodysenteriae strain G44 as it yields a high incidence of mucohaemorrhagic diarrhea with a reasonable cost.
Evolution and epidemic spread of SARS-CoV-2 in Brazil Candido, Darlan S; Claro, Ingra M; de Jesus, Jaqueline G ...
Science (American Association for the Advancement of Science),
09/2020, Letnik:
369, Številka:
6508
Journal Article
Recenzirano
Odprti dostop
Brazil currently has one of the fastest-growing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) epidemics in the world. Because of limited available data, assessments of the impact of ...nonpharmaceutical interventions (NPIs) on this virus spread remain challenging. Using a mobility-driven transmission model, we show that NPIs reduced the reproduction number from >3 to 1 to 1.6 in São Paulo and Rio de Janeiro. Sequencing of 427 new genomes and analysis of a geographically representative genomic dataset identified >100 international virus introductions in Brazil. We estimate that most (76%) of the Brazilian strains fell in three clades that were introduced from Europe between 22 February and 11 March 2020. During the early epidemic phase, we found that SARS-CoV-2 spread mostly locally and within state borders. After this period, despite sharp decreases in air travel, we estimated multiple exportations from large urban centers that coincided with a 25% increase in average traveled distances in national flights. This study sheds new light on the epidemic transmission and evolutionary trajectories of SARS-CoV-2 lineages in Brazil and provides evidence that current interventions remain insufficient to keep virus transmission under control in this country.
We describe the spectroscopic target selection for the Galaxy And Mass Assembly (GAMA) survey. The input catalogue is drawn from the Sloan Digital Sky Survey (SDSS) and UKIRT Infrared Deep Sky Survey ...(UKIDSS). The initial aim is to measure redshifts for galaxies in three 4°× 12° regions at 9, 12 and 14.5 h, on the celestial equator, with magnitude selections r < 19.4, z < 18.2 and KAB < 17.6 over all three regions, and r < 19.8 in the 12-h region. The target density is 1080 deg−2 in the 12-h region and 720 deg−2 in the other regions. The average GAMA target density and area are compared with completed and ongoing galaxy redshift surveys. The GAMA survey implements a highly complete star–galaxy separation that jointly uses an intensity-profile separator (Δsg=rpsf−rmodel as per the SDSS) and a colour separator. The colour separator is defined as Δsg,jk=J−K−f(g−i), where f(g−i) is a quadratic fit to the J−K colour of the stellar locus over the range 0.3 < g−i < 2.3. All galaxy populations investigated are well separated with Δsg,jk > 0.2. From 2 yr out of a 3-yr AAOmega program on the Anglo-Australian Telescope, we have obtained 79 599 unique galaxy redshifts. Previously known redshifts in the GAMA region bring the total up to 98 497. The median galaxy redshift is 0.2 with 99 per cent at z < 0.5. We present some of the global statistical properties of the survey, including K-band galaxy counts, colour–redshift relations and preliminary n(z).
Background
Although egg allergy is the most common food allergy in infants and young children, risk factors for egg allergy remain largely unknown. This study examined the relationship between ...environmental and demographic factors and egg allergy in a population‐based infant cohort.
Methods
In a study of 5276 infants (HealthNuts), infants underwent skin prick testing (SPT) to egg white at 12 months of age. Questionnaire data on relevant exposures were obtained. 699/873 (80%) infants eligible for oral food challenge (detectable wheal on SPT) attended for formal assessment of egg allergy status; 453 had confirmed egg allergy (positive challenge and SPT ≥ 2 mm). Associations between environmental and demographic factors and egg allergy were investigated using multivariable logistic regression.
Results
Children with older siblings and those with a pet dog at home were less likely to develop egg allergy by 1 year of age (adjusted OR aOR, 0.72; 95% CI, 0.62, 0.83 per sibling; and aOR, 0.72; 95% CI, 0.52, 0.99, respectively). Caesarean section delivery, antibiotic use in infancy, childcare attendance and maternal age were not associated with egg allergy. History of allergic disease in an immediate family member and having parents born in East Asia were strong risk factors for infantile egg allergy (aOR, 1.82; 95% CI, 1.40, 2.36; and aOR, 3.30; 95% CI, 2.45, 4.45, respectively).
Conclusions
Exposure in the first year of life to siblings and dogs may decrease the risk of subsequent egg allergy. Infants with a family history of allergy and those with parents born in East Asia are at increased risk of egg allergy.
Performance of the LHCb RICH detector at the LHC Adinolfi, M.; Aglieri Rinella, G.; Albrecht, E. ...
The European physical journal. C, Particles and fields,
05/2013, Letnik:
73, Številka:
5
Journal Article
Recenzirano
Odprti dostop
The LHCb experiment has been taking data at the Large Hadron Collider (LHC) at CERN since the end of 2009. One of its key detector components is the Ring-Imaging Cherenkov (RICH) system. This ...provides charged particle identification over a wide momentum range, from 2–100 GeV/
c
. The operation and control, software, and online monitoring of the RICH system are described. The particle identification performance is presented, as measured using data from the LHC. Excellent separation of hadronic particle types (
π
, K, p) is achieved.
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