Asthma prevalence is 339 million globally. ‘Severe asthma’ (SA) comprises subjects with uncontrolled asthma despite proper management.
To compare asthma from diverse ethnicities and environments.
A ...cross-sectional analysis of two adult cohorts, a Brazilian (ProAR) and a European (U-BIOPRED). U-BIOPRED comprised of 311 non-smoking with Severe Asthma (SAn), 110 smokers or ex-smokers with SA (SAs) and 88 mild to moderate asthmatics (MMA) while ProAR included 544 SA and 452 MMA. Although these projects were independent, there were similarities in objectives and methodology, with ProAR adopting operating procedures of U-BIOPRED.
Among SA subjects, age, weight, proportion of former smokers and FEV1 pre-bronchodilator were similar. The proportion of SA with a positive skin prick tests (SPT) to aeroallergens, the scores of sino-nasal symptoms and quality of life were comparable. In addition, blood eosinophil counts (EOS) and the % of subjects with EOS > 300 cells/μl were not different. The Europeans with SA however, were more severe with a greater proportion of continuous oral corticosteroids (OCS), worse symptoms and more frequent exacerbations. FEV1/FVC pre- and post-bronchodilator were lower among the Europeans. The MMA cohorts were less comparable in control and treatment, but similar in the proportion of allergic rhinitis, gastroesophageal reflux disease and EOS >3%.
ProAR and U-BIOPRED cohorts, with varying severity, ethnicity and environment have similarities, which provide the basis for global external validation of asthma phenotypes. This should stimulate collaboration between asthma consortia with the aim of understanding SA, which will lead to better management.
•The populations compared are of diverse ethnicity and socioeconomic status.•Europeans and Brazilians share multiple similarities, in spite of the differences.•In severe asthma (SA), age, weight and proportion of former smokers are similar.•FEV1% pre-BD and % of atopics are similar in those with SA across both continents.•The proportion of those with blood eosinophil counts > 300/μl is comparable in SA.
Botrytis cinerea, or gray mold, is a necrotrophic fungal pathogen of hundreds of plant species. The genetic diversity of B. cinerea may contribute to its broad host range; however, the level and ...structure of genetic variation at pathogenesis-associated loci has not been described. B. cinerea possesses six distinct cell-wall-degrading polygalacturonases (PGs), enzymes of demonstrated importance to pathogenesis and interaction with host plant defenses. Sequencing a collection of 34 B. cinerea isolates at three PG-encoding loci, BcPG1, BcPG2, and BcPG3, revealed limited evidence of host-mediated genetic subdivision within loci, yet suggested differences in the action of evolutionary forces among loci. BcPG1 and BcPG2 are highly polymorphic, particularly when compared with previously published data from nonpathogenicity loci, whereas BcPG3 is relatively conserved. Sequence variation at BcPG1 and BcPG2 did not appear to be associated with virulence on Arabidopsis leaves; however, BcPG2 variation showed a statistically significant association with growth rate on pectin. Rather than providing evidence for host-mediated genetic subdivision at individual PG loci, our data support specialization among PGs and the potential diversification of PGs interacting directly with host defenses.
Multidisciplinary investigations of the sequence at Beeches Pit, West Stow (Suffolk, UK), have a direct bearing the age of the Hoxnian Interglacial and its correlation with the continental ...Holsteinian and with the global marine record. At this site, glacial deposits (till and outwash gravels) referable to the Anglian Lowestoft Formation fill a subglacial channel cut in Chalk bedrock. Above these glacial deposits a series of interglacial sediments occurs, consisting of limnic, tufaceous and colluvial silts, lacking pollen but rich in shells, ostracods and vertebrates. Lower Palaeolithic flint artefacts of Acheulian character have also been recovered, including refitting examples. Charred material is abundant at certain horizons and many of the bones have been burned. Several discrete areas of burnt sediment are interpreted as hearths. The molluscan fauna comprises some 78 taxa and includes species of considerable zoogeographical and biostratigraphical importance. The land snail assemblage from the tufa consists of woodland taxa with no modern analogue, including species that are either extinct (e.g.
Zonitoides sepultus) or which no longer live in Britain (e.g.
Platyla polita,
P. similis,
Neniatlanta pauli). This is also the type locality of
Retinella (
Lyrodiscus)
skertchlyi, which belongs to a subgenus of zonitid land snail now living only on the Canary Islands. There are indications from this fauna (‘the
Lyrodiscus biome’) that the climate was wetter and perhaps warmer than the present day. The vertebrate fauna is also noteworthy with species of open habitats, such as rabbit (
Oryctolagus cf
. cuniculus), and of closed forest, such as squirrel (
Sciurus sp.) and garden dormouse (
Eliomys quercinus) present at different times. The occurrence of southern thermophiles, such as Aesculapian snake (
Zamenis longissimus), indicates temperatures warmer than those of eastern England today. The upper levels include much material reworked from the interglacial sediments, although there is clear faunal evidence for climatic deterioration. Both the molluscan and vertebrate faunas suggest correlation of the interglacial sediments with the Hoxnian. Uranium series dates from the tufa (∼455
ka BP), TL dates from burnt flints (414±30
ka BP) and a range of amino acid racemization data all support correlation of this interglacial with MIS 11. However, four OSL dates from sand beneath the interglacial sequence yield a mean age of 261±31
ka
BP, far younger than all other age determinations and far younger than implied by the biostratigraphy. Archaeologically the site is unusual in showing prolonged human occupation within closed deciduous forest and evidence for controlled use of fire in a Lower Palaeolithic context. Biostratigraphical correlations with other Lower Palaeolithic sites support the suggestion that Acheulian and Clactonian industries both occurred in southern Britain during the same substage of the Hoxnian, although not necessarily at precisely the same time. The characteristics of the MIS 11 interglacial in Britain are discussed in the light of evidence from Beeches Pit and elsewhere.
ABSTRACT We report on the discovery and validation of Kepler-452b, a transiting planet identified by a search through the 4 years of data collected by NASA's Kepler Mission. This possibly rocky ...planet orbits its G2 host star every days, the longest orbital period for a small ( ) transiting exoplanet to date. The likelihood that this planet has a rocky composition lies between 49% and 62%. The star has an effective temperature of 5757 85 K and a of 4.32 0.09. At a mean orbital separation of AU, this small planet is well within the optimistic habitable zone of its star (recent Venus/early Mars), experiencing only 10% more flux than Earth receives from the Sun today, and slightly outside the conservative habitable zone (runaway greenhouse/maximum greenhouse). The star is slightly larger and older than the Sun, with a present radius of and an estimated age of ∼6 Gyr. Thus, Kepler-452b has likely always been in the habitable zone and should remain there for another ∼3 Gyr.
Objectives
Appropriate use of imaging for adult patients with cervical spine (C‐spine) injuries in the emergency department (ED) is a longstanding issue. Guidance for C‐spine ordering exists; ...however, the effectiveness of the decision support implementation in the ED is not well studied. This systematic review examines the implementation and effectiveness of evidence‐based interventions aimed at reducing C‐spine imaging in adults presenting to the ED with neck trauma.
Methods
Six electronic databases and the gray literature were searched. Comparative intervention studies were eligible for inclusion. Two independent reviewers screened for study eligibility, study quality, and extracted data. The change in imaging was reported using individual odds ratios (ORs) with 95% confidence intervals (CIs) using random effects.
Results
A total of 990 unique citations were screened for relevance of which six before–after studies and one randomized controlled trial were included. None of the studies were assessed as high quality. Interventions consisted primarily of locally developed guidelines or established clinical decision rules such as the NEXUS or the Canadian C‐spine rule. Overall, implementation of interventions aimed at reducing C‐spine image ordering resulted in a statistically significant reduction in imaging (OR = 0.69, 95% CI = 0.51–0.93); however, heterogeneity was high (I2 = 82%). Subgroup analysis revealed no differences between studies that specified enrolling alert and stable patients compared to unspecified trauma (p = 0.81) or between studies employing multifaceted versus nonmultifaceted interventions (p = 0.66). While studies generally provided details on implementation strategies (e.g., teaching sessions, pocket cards, posters, computerized decision support) the effectiveness of these implementation strategies were frequently not reported.
Conclusion
There is moderate evidence regarding the effectiveness of interventions to reduce C‐spine image ordering in adult patients seen in the ED with neck trauma. Given the national and international focus on improving appropriateness and reducing unnecessary C‐spine imaging through campaigns such as Choosing Wisely, additional interventional research in this field is warranted.
Study objective: We sought to determine the sensitivity and specificity of the enzyme-linked immunosorbent assay (ELISA) D -dimer test in the diagnosis of pulmonary embolism (PE) in the adult ...emergency department population. Methods: A search of MEDLINE, EMBASE, and bibliographies of previous systematic reviews was conducted, with no language restriction. Experts in the field of PE research were contacted to identify unpublished studies. Prospective investigations involving a predominately outpatient population suspected of PE that used ELISA D -dimer tests were included. Two authors extracted data independently and assessed study quality on the basis of the patient spectrum and reference standard. Consensus was reached by means of conference. The analysis was based on a summary receiver operating characteristic curve and pooled estimates for sensitivity and specificity by using a random-effects model. Results: The search yielded 52 publications. No unpublished studies were found. Eleven studies met the inclusion criteria and provided a sample of 2,126 patients. The summary receiver operating characteristic curve analysis found significant heterogeneity among the 11 studies. Subgroup analysis of the 9 studies that used traditional ELISA D -dimer methods yielded the most valid pooled estimates, with a sensitivity of 0.94 (95% confidence interval CI 0.88 to 0.97) and a specificity of 0.45 (95% CI 0.36 to 0.55). Advanced age resulted in a lower specificity. A prolonged duration of symptoms decreased the sensitivity and specificity. Conclusion: The ELISA D -dimer test is highly sensitive but nonspecific for the detection of PE in the clinical setting. This test might help clinicians safely rule out PE, especially in the face of low and low-to-moderate pretest probabilities. Brown MD, Rowe BH, Reeves MJ, Bermingham JM, Goldhaber SZ. The accuracy of the enzyme-linked immunosorbent assay D -dimer test in the diagnosis of pulmonary embolism: a meta-analysis. Ann Emerg Med. August 2002;40:133-144.
Patients with type 2 diabetes mellitus are at increased risk of cardiovascular disease, partly owing to dyslipidaemia, which can be amenable to fibrate therapy. We designed the Fenofibrate ...Intervention and Event Lowering in Diabetes (FIELD) study to assess the effect of fenofibrate on cardiovascular disease events in these patients.
We did a multinational, randomised controlled trial with 9795 participants aged 50–75 years, with type 2 diabetes mellitus, and not taking statin therapy at study entry. After a placebo and a fenofibrate run-in phase, we randomly assigned patients (2131 with previous cardiovascular disease and 7664 without) with a total-cholesterol concentration of 3·0–6·5 mmol/L and a total-cholesterol/HDL-cholesterol ratio of 4·0 or more or plasma triglyceride of 1·0–5·0 mmol/L to micronised fenofibrate 200 mg daily (n=4895) or matching placebo (n=4900). Our primary outcome was coronary events (coronary heart disease death or non-fatal myocardial infarction); the outcome for prespecified subgroup analyses was total cardiovascular events (the composite of cardiovascular death, myocardial infarction, stroke, and coronary and carotid revascularisation). Analysis was by intention to treat. The study was prospectively registered (number ISRCTN 64783481).
Vital status was confirmed on all but 22 patients. Averaged over the 5 years' study duration, similar proportions in each group discontinued study medication (10% placebo
vs 11% fenofibrate) and more patients allocated placebo (17%) than fenofibrate (8%; p<0·0001) commenced other lipid treatments, predominantly statins. 5·9% (n=288) of patients on placebo and 5·2% (n=256) of those on fenofibrate had a coronary event (relative reduction of 11%; hazard ratio HR 0·89, 95% CI 0·75–1·05; p=0·16). This finding corresponds to a significant 24% reduction in non-fatal myocardial infarction (0·76, 0·62–0·94; p=0·010) and a non-significant increase in coronary heart disease mortality (1·19, 0·90–1·57; p=0·22). Total cardiovascular disease events were significantly reduced from 13·9% to 12·5% (0·89, 0·80–0·99; p=0·035). This finding included a 21% reduction in coronary revascularisation (0·79, 0·68–0·93; p=0·003). Total mortality was 6·6% in the placebo group and 7·3% in the fenofibrate group (p=0·18). Fenofibrate was associated with less albuminuria progression (p=0·002), and less retinopathy needing laser treatment (5·2%
vs 3·6%, p=0·0003). There was a slight increase in pancreatitis (0·5%
vs 0·8%, p=0·031) and pulmonary embolism (0·7%
vs 1·1%, p=0·022), but no other significant adverse effects.
Fenofibrate did not significantly reduce the risk of the primary outcome of coronary events. It did reduce total cardiovascular events, mainly due to fewer non-fatal myocardial infarctions and revascularisations. The higher rate of starting statin therapy in patients allocated placebo might have masked a moderately larger treatment benefit.
HLA-DR4 is associated with insulin-dependent diabetes mellitus (IDDM) in many populations. Many recent studies suggest that the DR4 effect is really due to DQ3.2, an allele of the nearby DQB1 locus. ...We used T cell clones, MAb, and allele-specific oligonucleotides to test IDDM and control subjects for DR4 subtypes (Dw4, Dw10, Dw13, and Dw14) and for DR4-associated DQB1 alleles (DQ3.1 and DQ3.2). We find that (a) IDDM is approximately equally associated with alleles of the DRB1 locus (Dw4 and Dw10, combined relative risk, RR = 6.4) and the DQB1 locus (DQ3.2, RR = 5.9); and (b) there is significant interaction, in a statistical sense, between these DR and DQ alleles in IDDM. The only IDDM-associated DR4 haplotypes were those carrying the IDDM-associated alleles at both loci (RR = 12.1); haplotypes with Dw4 or 10 but not DQ3.2, or vice versa, had a RR less than 1. Alternative explanations include: (a) that susceptibility requires specific allelic products of both DR and DQ loci; (b) that the combination of certain DR and DQ alleles marks haplotypes with the true susceptibility allele at a third locus; or (c) that Dw4 and 10 mark haplotypes with an allele at another locus that interacts with DQ3.2. As discussed, this third locus is unlikely to be DQA1 (DQ alpha). The data thus are not easily reconciled with an exclusive effect of HLA-DQ. This information increases our ability to predict IDDM by genetic typing: in the population studied, heterozygotes DR3/DQ3.2, Dw4 or DR3/DQ3.2, Dw10 had a relative risk of 38.0 and an absolute risk of 1 in 15.
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