ObjectivesTo assess practice in the care of adults with suspected community-acquired bacterial meningitis in the UK and Ireland.DesignRetrospective cohort study.Setting64 UK and Irish ...hospitals.Participants1471 adults with community-acquired meningitis of any aetiology in 2017.ResultsNone of the audit standards, from the 2016 UK Joint Specialists Societies guideline on diagnosis and management of meningitis, were met in all cases. With respect to 20 of 30 assessed standards, clinical management provided for patients was in line with recommendations in less than 50% of cases. 45% of patients had blood cultures taken within an hour of admission, 0.5% had a lumbar puncture within 1 hour, 26% within 8 hours. 28% had bacterial molecular diagnostic tests on cerebrospinal fluid. Median time to first dose of antibiotics was 3.2 hours (IQR 1.3–9.2). 80% received empirical parenteral cephalosporins. 55% ≥60 years and 31% of immunocompromised patients received anti-Listeria antibiotics. 21% received steroids. Of the 1471 patients, 20% had confirmed bacterial meningitis. Among those with bacterial meningitis, pneumococcal aetiology, admission to intensive care and initial Glasgow Coma Scale Score less than 14 were associated with in-hospital mortality (adjusted OR (aOR) 2.08, 95% CI 0.96 to 4.48; aOR 4.28, 95% CI 1.81 to 10.1; aOR 2.90, 95% CI 1.26 to 6.71, respectively). Dexamethasone therapy was weakly associated with a reduction in mortality in both those with proven bacterial meningitis (aOR 0.57, 95% CI 0.28 to 1.17) and with pneumococcal meningitis (aOR 0.47, 95% CI 0.20 to 1.10).ConclusionThis study demonstrates that clinical care for patients with meningitis in the UK is not in line with current evidence-based national guidelines. Diagnostics and therapeutics should be targeted for quality improvement strategies. Work should be done to improve the impact of guidelines, understand why they are not followed and, once published, ensure they translate into changed practice.
This short history of the Dorper sheep traces its background and the steps taken to develop that breed in South Africa. The most important traits considered for the developing of the Dorper are ...listed and the breeding system outlined. The development of the White Dorper is also detailed and the breed improvement programs are indicated.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Bone Morphogenetic Proteins (BMPs) are members of the Transforming Growth Factor-β (TGF-β) signalling protein superfamily. BMPs play important and diverse roles in cell-cell signalling, including ...establishing cell fate during the development of vertebrate embryos. Their activity is antagonised in vivo by a number of proteins such as noggin, which sequester BMP ligands, preventing them from binding to BMP receptors. This thesis describes studies to establish a binary genetic approach combined with a ligand trap system to manipulate BMP signalling in the frog embryo. This system has been used to investigate the roles of BMP signalling in dorso-ventral patterning of the forebrain Xenopus tropicalis. The binary system described utilises a variety of tissue- or region-specific gene promoters to drive expression of the GAL4 transcriptional activator. Such transgenic "driver" lines can be crossed with a "responder" line in which expression of a membrane-tethered fusion protein comprising human Noggin fused to GFP is regulated by a synthetic promoter responsive to GAL4 (UAS-flognog). Transient expression assays confirmed the effectiveness of the "responder" line, GAL4 transactivation of UAS-flognog resulted in the expression of Flognog and an expansion of neural progenitor tissue, indicated by the X-Sox3 marker. In a binary cross with the Otx2-gal4 driver line, targeted GAL4 transactivation lead to a decrease in phospho-Smad-1 staining in the anterior CNS and eye in a proportion of cross embryos. Such a cross resulted in embryos showing an open neural tube and alterations in both Pax6 (dorsal) and X-<U13 (ventral) forebrain markers, further indicating the efficacy of the binary, ligand-trap strategy. In order to achieve temporal control on the activity of the UAS-flognog responder line in the telencephalon, an inducible driver line comprising the Pax6 promoter driving hormone-inducible GalPR (an inducible chimeric GAL4) was created. In binary crosses with a UAS-gfp reporter line, GFP expression was detected in the forebrain, hindbrain and spinal cord only in the presence of the steroid hormone, RU486. Similarly, a second driver line, N-tubulin-GalPR yielded inducible GFP expression in the developing brain, spinal cord and lens tissue in the presence of RU486. In conclusion, these findings are evidence that the binary ligand trap approach is functional and can cause targeted knockdown of BMP signalling, resulting in alterations in neural development and patterning. Furthermore, using an inducible version of this approach, Flognog (or any other target gene) can be expressed in the telencephalon in a RU486-inducible manner.
Bone Morphogenetic Proteins (BMPs) are members of the Transforming Growth Factor-beta (TGF-beta) signalling protein superfamily. BMPs play important and diverse roles in cell-cell signalling, ...including establishing cell fate during the development of vertebrate embryos. Their activity is antagonised in vivo by a number of proteins such as noggin, which sequester BMP ligands, preventing them from binding to BMP receptors. This thesis describes studies to establish a binary genetic approach combined with a ligand trap system to manipulate BMP signalling in the frog embryo. This system has been used to investigate the roles of BMP signalling in dorso-ventral patterning of the forebrain Xenopus tropicalis. The binary system described utilises a variety of tissue- or region-specific gene promoters to drive expression of the GAL4 transcriptional activator. Such transgenic "driver" lines can be crossed with a "responder" line in which expression of a membrane-tethered fusion protein comprising human Noggin fused to GFP is regulated by a synthetic promoter responsive to GAL4 (UAS-flognog). Transient expression assays confirmed the effectiveness of the "responder" line, GAL4 transactivation of UAS-flognog resulted in the expression of Flognog and an expansion of neural progenitor tissue, indicated by the X-Sox3 marker. In a binary cross with the Otx2-gal4 driver line, targeted GAL4 transactivation lead to a decrease in phospho-Smad-1 staining in the anterior CNS and eye in a proportion of cross embryos. Such a cross resulted in embryos showing an open neural tube and alterations in both Pax6 (dorsal) and X-<U13 (ventral) forebrain markers, further indicating the efficacy of the binary, ligand-trap strategy. In order to achieve temporal control on the activity of the UAS-flognog responder line in the telencephalon, an inducible driver line comprising the Pax6 promoter driving hormone-inducible GalPR (an inducible chimeric GAL4) was created. In binary crosses with a UAS-gfp reporter line, GFP expression was detected in the forebrain, hindbrain and spinal cord only in the presence of the steroid hormone, RU486. Similarly, a second driver line, N-tubulin-GalPR yielded inducible GFP expression in the developing brain, spinal cord and lens tissue in the presence of RU486. In conclusion, these findings are evidence that the binary ligand trap approach is functional and can cause targeted knockdown of BMP signalling, resulting in alterations in neural development and patterning. Furthermore, using an inducible version of this approach, Flognog (or any other target gene) can be expressed in the telencephalon in a RU486-inducible manner.
Abstract
We compare infrared surface brightness fluctuation (IR SBF) distances measured in galaxies that have hosted type Ia supernovae (SNe Ia) to distances estimated from SNe Ia light-curve fits. ...We show that the properties of the SNe Ia found in IR SBF hosts are very different from those exploding in Cepheid calibrators, therefore this is a direct test of systematic uncertainties on the estimation of the Hubble constant (
H
0
) using SNe. The IR SBF results from Jensen et al. provide a large and uniformly measured sample of IR SBF distances which we directly compare with the distances to 25 SN Ia host galaxies. We divide the Hubble flow SNe Ia into subsamples that best match the divergent SN properties seen in the IR SBF hosts and Cepheid hosts. We further divide the SNe Ia into a sample with light-curve widths and host masses that are congruent to those found in the SBF-calibrated hosts. We refit the light-curve stretch and color correlations with luminosity, and use these revised parameters to calibrate a sample of “Hubble flow” SNe Ia with IR SBF calibrators. Relative to the Hubble flow sample, the average calibrator distance moduli vary by 0.03 mag depending on the SN Ia subsample examined and this adds a 1.8% systematic uncertainty to our Hubble constant estimate. Based on the IRSBF calibrators,
H
0
= 74.6 ± 0.9(stat) ± 2.7(syst) km s
−1
Mpc
−1
, which is consistent with the Hubble constant derived from SNe Ia calibrated from Cepheid variables. We conclude that IR SBFs provide reliable calibration of SNe Ia with a precision comparable to Cepheid calibrators, and with a significant saving in telescope time.
The carbon gain in restored logged forest
There is currently great interest in the capacity of global forest to store carbon and hence contribute to the mitigation of climate change in the coming ...decades. In a study of Southeast Asian tropical forest, Philipson
et al.
show that active restoration of logged forests generates higher rates of carbon accumulation than naturally regenerating forest. To estimate the economic feasibility of restoration treatments, they modeled the carbon price required to offset the cost of restoration, finding that the highest prices seen in recent years would be needed to approach those that could offset restoration costs. These results are important for tropical forest policy, establishing the importance of restoration for the carbon recovery potential of tropical forests.
Science
, this issue p.
838
Restoration of logged tropical forests will be incentivized by carbon prices, consistent with the 2016 Paris climate agreement.
More than half of all tropical forests are degraded by human impacts, leaving them threatened with conversion to agricultural plantations and risking substantial biodiversity and carbon losses. Restoration could accelerate recovery of aboveground carbon density (ACD), but adoption of restoration is constrained by cost and uncertainties over effectiveness. We report a long-term comparison of ACD recovery rates between naturally regenerating and actively restored logged tropical forests. Restoration enhanced decadal ACD recovery by more than 50%, from 2.9 to 4.4 megagrams per hectare per year. This magnitude of response, coupled with modal values of restoration costs globally, would require higher carbon prices to justify investment in restoration. However, carbon prices required to fulfill the 2016 Paris climate agreement $40 to $80 (USD) per tonne carbon dioxide equivalent would provide an economic justification for tropical forest restoration.
Abstract
We measured high-quality surface brightness fluctuation (SBF) distances for a sample of 63 massive early-type galaxies using the WFC3/IR camera on the Hubble Space Telescope. The median ...uncertainty on the SBF distance measurements is 0.085 mag, or 3.9% in distance. Achieving this precision at distances of 50–100 Mpc required significant improvements to the SBF calibration and data analysis procedures for WFC3/IR data. Forty-two of the galaxies are from the MASSIVE Galaxy Survey, a complete sample of massive galaxies within ∼100 Mpc; the SBF distances for these will be used to improve the estimates of the stellar and central supermassive black hole masses in these galaxies. Twenty-four of the galaxies are Type Ia supernova hosts, useful for calibrating SN Ia distances for early-type galaxies and exploring possible systematic trends in the peak luminosities. Our results demonstrate that the SBF method is a powerful and versatile technique for measuring distances to galaxies with evolved stellar populations out to 100 Mpc and constraining the local value of the Hubble constant.
Active sensing is the process of moving sensors to extract task-specific information. Whisker touch is often referred to as an active sensory system as whiskers are moved with purposeful control. ...Even though whisker movements are found in many species, it is unknown whether any animal can make task-specific movements with their whiskers. California sea lions (Zalophus californianus) make large, purposeful whisker movements and are capable of performing many whisker-related discrimination tasks. Therefore, California sea lions are an ideal species to explore the active nature of whisker touch sensing. Here, we show that California sea lions can make task-specific whisker movements. California sea lions move their whiskers with large amplitudes around object edges to judge size, make smaller, lateral stroking movements to judge texture and make very small whisker movements during a visual task. These findings, combined with the ease of training mammals and measuring whisker movements, makes whiskers an ideal system for studying mammalian perception, cognition and motor control.
Laterality of epithelial ovarian tumors may reflect the underlying carcinogenic pathways and origins of tumor cells.
We pooled data from 9 prospective studies participating in the Ovarian Cancer ...Cohort Consortium. Information on measures of tumor size or tumor dominance was extracted from surgical pathology reports or obtained through cancer registries. We defined dominant tumors as those restricted to one ovary or where the dimension of one ovary was at least twice as large as the other, and nondominant tumors as those with similar dimensions across the two ovaries or peritoneal tumors. Competing risks Cox models were used to examine whether associations with reproductive and hormonal risk factors differed by ovarian tumor dominance.
Of 1,058 ovarian cancer cases with tumor dominance information, 401 were left-dominant, 363 were right-dominant, and 294 were nondominant. Parity was more strongly inversely associated with risk of dominant than nondominant ovarian cancer (
= 0.004). Ever use of oral contraceptives (OC) was associated with lower risk of dominant tumors, but was not associated with nondominant tumors (
= 0.01). Higher body mass index was associated with higher risk of left-dominant tumors, but not significantly associated with risk of right-dominant or nondominant tumors (
= 0.08).
These data suggest that reproductive and hormonal risk factors appear to have a stronger impact on dominant tumors, which may have an ovarian or endometriosis origin.
Examining the associations of ovarian cancer risk factors by tumor dominance may help elucidate the mechanisms through which these factors influence ovarian cancer risk.
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