Stepwise Earth oxygenation is an inherent property of global biogeochemical cycling

Oxygenation of Earth’s atmosphere and oceans occurred across three major steps during the Paleoproterozoic, Neoproterozoic, and Paleozoic eras, with each increase having profound consequences for the biosphere. Biological or tectonic revolutions have been proposed to explain each of these stepwise increases in oxygen, but the principal driver of each event remains unclear. Here we show, using a theoretical model, that the observed oxygenation steps are a simple consequence of internal feedbacks in the long-term biogeochemical cycles of carbon, oxygen, and phosphorus, and that there is no requirement for a specific stepwise external forcing to explain the course of Earth surface oxygenation. We conclude that Earth’s oxygenation events are entirely consistent with gradual oxygenation of the planetary surface after the evolution of oxygenic photosynthesis

Predictors of severe asthma attack re-attendance in Ecuadorian children: a cohort study.

Asthma is a common cause of emergency care attendance in low- and middle-income countries (LMICs). While few prospective studies of predictors for emergency care attendance have been undertaken in high-income countries, none have been performed in a LMIC.We followed a cohort of 5-15-year-old children treated for asthma attacks in emergency rooms of public health facilities in Esmeraldas City, Ecuador. We collected blood and nasal wash samples, and performed spirometry and exhaled nitric oxide fraction measurements. We explored potential predictors for recurrence of severe asthma attacks requiring emergency care over 6 months' follow-up.We recruited 283 children of whom 264 (93%) were followed-up for ≥6 months or until their next asthma attack. Almost half (46%) had a subsequent severe asthma attack requiring emergency care. Predictors of recurrence in adjusted analyses were (adjusted OR, 95% CI) younger age (0.87, 0.79-0.96 per year), previous asthma diagnosis (2.2, 1.2-3.9), number of parenteral corticosteroid courses in previous year (1.3, 1.1-1.5), food triggers (2.0, 1.1-3.6) and eczema diagnosis (4.2, 1.02-17.6). A parsimonious Cox regression model included the first three predictors plus urban residence as a protective factor (adjusted hazard ratio 0.69, 95% CI 0.50-0.95). Laboratory and lung function tests did not predict recurrence.Factors independently associated with recurrent emergency attendance for asthma attacks were identified in a low-resource LMIC setting. This study suggests that a simple risk-assessment tool could potentially be created for emergency rooms in similar settings to identify higher-risk children on whom limited resources might be better focused

The iBRA (implant breast reconstruction evaluation) study: protocol for a prospective multi-centre cohort study to inform the feasibility, design and conduct of a pragmatic randomised clinical trial comparing new techniques of implant-based breast reconstruction.

BACKGROUND: Implant-based breast reconstruction (IBBR) is the most commonly performed reconstructive procedure in the UK. The introduction of techniques to augment the subpectoral pocket has revolutionised the procedure, but there is a lack of high-quality outcome data to describe the safety or effectiveness of these techniques. Randomised controlled trials (RCTs) are the best way of comparing treatments, but surgical RCTs are challenging. The iBRA (implant breast reconstruction evaluation) study aims to determine the feasibility, design and conduct of a pragmatic RCT to examine the effectiveness of approaches to IBBR. METHODS/DESIGN: The iBRA study is a trainee-led research collaborative project with four phases:Phase 1 - a national practice questionnaire (NPQ) to survey current practicePhase 2 - a multi-centre prospective cohort study of patients undergoing IBBR to evaluate the clinical and patient-reported outcomesPhase 3- an IBBR-RCT acceptability survey and qualitative work to explore patients' and surgeons' views of proposed trial designs and candidate outcomes.Phase 4 - phases 1 to 3 will inform the design and conduct of the future RCT All centres offering IBBR will be encouraged to participate by the breast and plastic surgical professional associations (Association of Breast Surgery and British Association of Plastic Reconstructive and Aesthetic Surgeons). Data collected will inform the feasibility of undertaking an RCT by defining current practice and exploring issues surrounding recruitment, selection of comparator arms, choice of primary outcome, sample size, selection criteria, trial conduct, methods of data collection and feasibility of using the trainee collaborative model to recruit patients and collect data. DISCUSSION: The preliminary work undertaken within the iBRA study will determine the feasibility, design and conduct of a definitive RCT in IBBR. It will work with the trainee collaborative to build capacity by creating an infrastructure of research-active breast and plastic surgeons which will facilitate future high-quality research that will ultimately improve outcomes for all women seeking reconstructive surgery. TRIAL REGISTRATION: ISRCTN37664281

Which Test Is Best? A Cluster-Randomized Controlled Trial of a Risk Calculator and Recommendations on Colorectal Cancer Screening Behaviour in General Practice

Introduction: This cluster-randomized controlled trial aimed to assess the effect of the "Which test is best?"tool on risk-appropriate screening (RAS) and colorectal cancer (CRC) screening uptake. Methods: General practices in Sydney and Melbourne, Australia, and a random sub-sample of 460 patients (aged 25-74 years) per practice were invited by post. Clusters were computer randomized independently of the researchers to an online CRC risk calculator with risk-based recommendations versus usual care. Primary and secondary outcomes were RAS and screening uptake via self-reported 5-year screening behaviour after 12 months follow-up. The usual care group (UCG) also self-reported 5-year CRC screening behaviour at 12 month post-randomization. Results: Fifty-six practices were randomized (27 to the intervention and 29 to the control, 55 practices participated) with 818 intervention and 677 controls completing the primary outcome measure. The intervention significantly increased RAS in high-risk participants compared with UCG (80.0% vs. 64.0%, respectively; OR = 3.14, 95% CI: 1.25-7.96) but not in average-risk (44.9% vs. 49.5%, respectively; OR = 0.97, 95% CI: 0.99-1.12) or moderate-risk individuals (67.9% vs. 81.1%, respectively; OR = 0.40, 95% CI: 0.12-1.33). Faecal occult blood testing uptake over 12 months was increased compared with the UCG (24.9% vs. 15.1%; adjusted OR = 1.66, 95% CI: 1.24-2.22), and there was a non-significant increase in colonoscopies during the same period (16.6% vs. 12.2%; adjusted OR = 1.42, 95% CI: 0.97-2.08). Conclusion: An online CRC risk calculator with risk-based screening recommendations increased RAS in high-risk participants and improved screening uptake overall within a 12-month follow-up period. Such tools may be useful for facilitating the uptake of risk-based screening guidelines

Development of Iron Speciation Reference Materials for Palaeoredox Analysis

The development and application of geochemical techniques to identify redox conditions in modern and ancient aquatic environments has intensified over recent years. Iron (Fe) speciation has emerged as one of the most widely used procedures to distinguish different redox regimes in both the water column and sediments, and is the main technique used to identify oxic, ferruginous (anoxic, Fe(II) containing) and euxinic (anoxic, sulfidic) water column conditions. However, an international sediment reference material has never been developed. This has led to concern over the consistency of results published by the many laboratories that now utilise the technique. Here, we report an interlaboratory comparison of four Fe speciation reference materials for palaeoredox analysis, which span a range of compositions and reflect deposition under different redox conditions. We provide an update of extraction techniques used in Fe speciation, and assess the effects of both test portion mass, and the use of different analytical procedures, on the quantification of different Fe fractions in sedimentary rocks. While atomic adsorption spectroscopy and inductively coupled plasma‐optical emission spectrometry produced comparable Fe measurements for all extraction stages, the use of ferrozine consistently underestimated Fe in the extraction step targeting mixed ferrous‐ferric minerals such as magnetite. We therefore suggest that the use of ferrozine is discontinued for this Fe pool. Finally, we report the combined data of four independent Fe speciation laboratories to characterise the Fe speciation composition of the reference materials. These reference materials are available to the community to provide an essential validation of in‐house Fe speciation measurements

Cost-effectiveness of community versus hospital eye service follow-up for patients with quiescent treated age-related macular degeneration alongside the ECHoES randomised trial

Objectives To assess the cost-effectiveness of optometrist-led follow-up monitoring reviews for patients with quiescent neovascular age-related macular degeneration (nAMD) in community settings (including high street opticians) compared with ophthalmologist-led reviews in hospitals. Design A model based cost-effectiveness analysis with a 4-week time horizon, based on a ‘virtual’ non-inferiority randomised trial designed to emulate a parallel group design. Setting A virtual internet-based clinical assessment, conducted at community optometry practices, and hospital ophthalmology clinics. Participants Ophthalmologists with experience in the age-related macular degeneration service; fully qualified optometrists not participating in nAMD shared care schemes. Interventions The participating optometrists and ophthalmologists classified lesions from vignettes and were asked to judge whether any retreatment was required. Vignettes comprised clinical information, colour fundus photographs and optical coherence tomography images. Participants’ classifications were validated against experts’ classifications (reference standard). Resource use and cost information were attributed to these retreatment decisions. Main Outcome Measures Correct classification of whether further treatment is needed, compared with a reference standard. Results The mean cost per assessment, including the subsequent care pathway, was £411 for optometrists and £397 for ophthalmologists: a cost difference of £13 (95% CI: -£18, £45). Optometrists were non-inferior to ophthalmologists with respect to the overall percentage of lesions correctly assessed (difference: -1.0%; 95% CI: -4.5%, 2.5%). Conclusions In the base case analysis, the slightly larger number of incorrect retreatment decisions by optometrists led to marginally and non-significantly higher costs. Sensitivity analyses that reflected different practices across eye hospitals indicate that shared care pathways between optometrists and ophthalmologists can be identified which may reduce demands on scant hospital resources, although in light of the uncertainty around differences in outcome and cost it remains unclear whether the differences between the two care pathways are significant in economic terms. </p

Using molecular and crowd‐sourcing methods to assess breeding ground diet of a migratory brood parasite of conservation concern

This is the author accepted manuscript. The final version is available from Wiley via the DOI in this recordThe research data supporting this publication are openly available from Dryad at https://doi.org/10.5061/dryad.v6wwpzgsp and from NCBI Sequence Read Archive under BioProject number PRJNA606798Breeding ground food availability is critical to the survival and productivity of adult birds. The common cuckoo Cuculus canorus is a brood‐parasitic Afro‐Palearctic migrant bird exhibiting long‐term (breeding) population declines in many European countries. Variation in population trend between regions and habitats suggests breeding ground drivers such as adult food supply. However, cuckoo diet has not been studied in detail since before the most significant population declines in Europe began in the mid‐1980s. 20th century studies of cuckoo diet largely comprised field observations likely to carry bias towards larger prey taxa. Here we demonstrate the potential value of 1) using high‐throughput DNA sequencing of invertebrate prey in faeces to determine cuckoo diet with minimal bias towards large prey taxa, and 2) using crowd‐sourced digital photographs from across Britain to identify lepidopteran cuckoo prey taxa during recent years post‐decline (2005‐2016). DNA analysis found a high frequency of Lepidoptera, including moths of family Lasiocampidae, prominent within the past literature, but also grasshoppers (Orthoptera) and flies (Diptera) that may be overlooked by field observation methodologies. The range of larval lepidopteran prey identified from photographs largely agreed with those previously documented, with potential signs of reduced diversity, and identities of key adult prey taxa were supported by molecular results. Notably, many identified cuckoo prey taxa have shown severe declines due to agricultural intensification, suggesting this has driven spatial patterns of cuckoo loss. Landscape‐scale, lowland rewilding interventions provide opportunities to understand the scale of reversal of previous agricultural intensification that may be necessary to restore prey populations sufficiently to permit recolonization by cuckoos.Dartmoor National Park AuthorityNatural Environment Research Council (NERC)University of ExeterRoyal Society for the Protection of Birds (RSPB

Measuring quality of life in patients with abdominal wall hernias: a systematic review of available tools

Introduction Abdominal wall herniation (AWH) is an increasing problem for patients, surgeons, and healthcare providers. Surgical-site specific outcomes, such as infection, recurrence, and mesh explantation, are improving; however, successful repair still exposes the patient to what is often a complex major operation aimed at improving quality of life. Quality-of-life (QOL) outcomes, such as aesthetics, pain, and physical and emotional functioning, are less often and less well reported. We reviewed QOL tools currently available to evaluate their suitability. Methods A systematic review of the literature in compliance with PRISMA guidelines was performed between 1st January 1990 and 1st May 2019. English language studies using validated quality-of-life assessment tool, whereby outcomes using this tool could be assessed were included. Results Heterogeneity in the QOL tool used for reporting outcome was evident throughout the articles reviewed. AWH disease-specific tools, hernia-specific tools, and generic tools were used throughout the literature with no obviously preferred or dominant method identified. Conclusion Despite increasing acknowledgement of the need to evaluate QOL in patients with AWH, no tool has become dominant in this field. Assessment, therefore, of the impact of certain interventions or techniques on quality of life remains difficult and will continue to do so until an adequate standardised outcome measurement tool is available

Expansion of CD4+CD25+ helper T cells without regulatory function in smoking and COPD

<p>Abstract</p> <p>Background</p> <p>Regulatory T cells have been implicated in the pathogenesis of COPD by the increased expression of CD25 on helper T cells along with enhanced intracellular expression of FoxP3 and low/absent CD127 expression on the cell surface.</p> <p>Method</p> <p>Regulatory T cells were investigated in BALF from nine COPD subjects and compared to fourteen smokers with normal lung function and nine never-smokers.</p> <p>Results</p> <p>In smokers with normal lung function, the expression of CD25⁺CD4⁺was increased, whereas the proportions of FoxP3⁺and CD127⁺were unchanged compared to never-smokers. Among CD4⁺cells expressing high levels of CD25, the proportion of FoxP3⁺cells was decreased and the percentage of CD127⁺was increased in smokers with normal lung function. CD4⁺CD25⁺cells with low/absent CD127 expression were increased in smokers with normal lung function, but not in COPD, when compared to never smokers.</p> <p>Conclusion</p> <p>The reduction of FoxP3 expression in BALF from smokers with normal lung function indicates that the increase in CD25 expression is not associated with the expansion of regulatory T cells. Instead, the high CD127 and low FoxP3 expressions implicate a predominantly non-regulatory CD25⁺helper T-cell population in smokers and stable COPD. Therefore, we suggest a smoking-induced expansion of predominantly activated airway helper T cells that seem to persist after COPD development.</p

Analysis of Microsatellite Variation in Drosophila melanogaster with Population-Scale Genome Sequencing

Genome sequencing technologies promise to revolutionize our understanding of genetics, evolution, and disease by making it feasible to survey a broad spectrum of sequence variation on a population scale. However, this potential can only be realized to the extent that methods for extracting and interpreting distinct forms of variation can be established. The error profiles and read length limitations of early versions of next-generation sequencing technologies rendered them ineffective for some sequence variant types, particularly microsatellites and other tandem repeats, and fostered the general misconception that such variants are inherently inaccessible to these platforms. At the same time, tandem repeats have emerged as important sources of functional variation. Tandem repeats are often located in and around genes, and frequent mutations in their lengths exert quantitative effects on gene function and phenotype, rapidly degrading linkage disequilibrium between markers and traits. Sensitive identification of these variants in large-scale next-gen sequencing efforts will enable more comprehensive association studies capable of revealing previously invisible associations. We present a population-scale analysis of microsatellite repeats using whole-genome data from 158 inbred isolates from the Drosophila Genetics Reference Panel, a collection of over 200 extensively phenotypically characterized isolates from a single natural population, to uncover processes underlying repeat mutation and to enable associations with behavioral, morphological, and life-history traits. Analysis of repeat variation from next-generation sequence data will also enhance studies of genome stability and neurodegenerative diseases