Dissolved organic carbon uptake in streams: A review and assessment of reach‐scale measurements

Quantifying the role that freshwater ecosystems play in the global carbon cycle requires accurate measurement and scaling of dissolved organic carbon (DOC) removal in river networks. We reviewed reach‐scale measurements of DOC uptake from experimental additions of simple organic compounds or leachates to inform development of aquatic DOC models that operate at the river network, regional, or continental scale. Median DOC uptake velocity (vf) across all measurements was 2.28 mm min−1. Measurements using simple compound additions resulted in faster vf (2.94 mm min−1) than additions of leachates (1.11 mm min−1). We also reviewed published data of DOC bioavailability for ambient stream water and leaf leachate DOC from laboratory experiments. We used these data to calculate and apply a correction factor to leaf leachate uptake velocity to estimate ambient stream water DOC uptake rates at the reach scale. Using this approach, we estimated a median ambient stream DOC vf of 0.26 mm min−1. Applying these DOC vf values (0.26, 1.11, 2.28, and 2.94 mm min−1) in a river network inverse model in seven watersheds revealed that our estimated ambient DOC vf value is plausible at the network scale and 27 to 45% of DOC input was removed. Applying the median measured simple compound or leachate vf in whole river networks would require unjustifiably high terrestrial DOC inputs to match observed DOC concentrations at the basin mouth. To improve the understanding and importance of DOC uptake in fluvial systems, we recommend using a multiscale approach coupling laboratory assays, with reach‐scale measurements, and modeling

Reduction in overt and silent stroke recurrence rate following cerebral revascularization surgery in children with sickle cell disease and severe cerebral vasculopathy

Background Children with sickle cell disease (SCD) and moyamoya may benefit from indirect cerebral revascularization surgery in addition to chronic blood transfusion therapy for infarct prevention. We sought to compare overt and silent infarct recurrence rates in children with SCD undergoing revascularization. Methods This was a retrospective cohort study of all children with SCD and moyamoya treated at two children’s hospitals. Clinical events and imaging studies were reviewed. Results Twenty-seven children with SCD and confirmed moyamoya receiving chronic transfusion therapy were identified, of whom 12 underwent indirect cerebral revascularization. Two subjects had post-operative transient ischemic attacks and another had a subarachnoid blood collection, none of which caused permanent consequences. Two subjects had surgical wound infections. Among these 12 children, the rate of overt and silent infarct recurrence decreased from 13.4 infarcts/100 patient-years before revascularization to 0 infarcts/100 patient-years after revascularization (p=0.0057); the post-revascularization infarct recurrence rate was also significantly lower than the overall infarct recurrence of 8.87 infarcts/100 patient-years in 15 children without cerebral revascularization (p=0.025). Conclusion The rate of overt and silent infarct recurrence was significantly lower following indirect cerebral revascularization. A prospective study of cerebral revascularization in children with SCD is needed

Frog nest foams exhibit pharmaceutical foam-like properties

Foams have frequently been used as systems for the delivery of cosmetic and therapeutic molecules; however, there is high variability in the foamability and long-term stability of synthetic foams. The development of pharmaceutical foams that exhibit desirable foaming properties, delivering appropriate amounts of the active pharmaceutical ingredient (API) and that have excellent biocompatibility is of great interest. The production of stable foams is rare in the natural world; however, certain species of frogs have adopted foam production as a means of providing a protective environment for their eggs and larvae from predators and parasites, to prevent desiccation, to control gaseous exchange, to buffer temperature extremes, and to reduce UV damage. These foams show great stability (up to 10 days in tropical environments) and are highly biocompatible due to the sensitive nature of amphibian skin. This work demonstrates for the first time that nests of the túngara frog ( Engystomops pustulosus ) are stable ex situ with useful physiochemical and biocompatible properties and are capable of encapsulating a range of compounds, including antibiotics. These protein foam mixtures share some properties with pharmaceutical foams and may find utility in a range of pharmaceutical applications such as topical drug delivery systems

Developing theory-based SMS messages to support retention in clinical trials : a mixed methods approach

The author(s) disclosed receipt of the following financial support for the research, authorship and/or publication of this article: This report is independent research supported by the National Institute for Health Research NIHR Advanced Fellowship, Dr Samuel Smith NIHR300588. The views expressed in this publication are those of the author(s) and not necessarily those of the NHS, the National Institute for Health Research or the Department of Health and Social Care. The funders had no role in the design of the study, data collection, analysis, interpretation of data and in the writing of this manuscript. Dr Smith also acknowledges the support of a Yorkshire Cancer Research Fellowship. Prof French is supported by the NIHR Manchester Biomedical Research Centre (IS-BRC1215-20007).Peer reviewedPublisher PD

High prevalence and two dominant host-specific genotypes of Coxiella burnetii in U.S. milk

BackgroundCoxiella burnetii causes Q fever in humans and Coxiellosis in animals; symptoms range from general malaise to fever, pneumonia, endocarditis and death. Livestock are a significant source of human infection as they shed C. burnetii cells in birth tissues, milk, urine and feces. Although prevalence of C. burnetii is high, few Q fever cases are reported in the U.S. and we have a limited understanding of their connectedness due to difficulties in genotyping. Here, we develop canonical SNP genotyping assays to evaluate spatial and temporal relationships among C. burnetii environmental samples and compare them across studies. Given the genotypic diversity of historical collections, we hypothesized that the current enzootic of Coxiellosis is caused by multiple circulating genotypes. We collected A) 23 milk samples from a single bovine herd, B) 134 commercial bovine and caprine milk samples from across the U.S., and C) 400 bovine and caprine samples from six milk processing plants over three years.ResultsWe detected C. burnetii DNA in 96% of samples with no variance over time. We genotyped 88.5% of positive samples; bovine milk contained only a single genotype (ST20) and caprine milk was dominated by a second type (mostly ST8).ConclusionsThe high prevalence and lack of genotypic diversity is consistent with a model of rapid spread and persistence. The segregation of genotypes between host species is indicative of species-specific adaptations or dissemination barriers and may offer insights into the relative lack of human cases and characterizing genotypes

CONservative TReatment of Appendicitis in Children – a randomised controlled feasibility Trial (CONTRACT)

Objective To establish the feasibility of a multicentre randomised controlled trial to assess the effectiveness and cost-effectiveness of a non-operative treatment pathway compared with appendicectomy in children with uncomplicated acute appendicitis.Design Feasibility randomised controlled trial with embedded qualitative study to inform recruiter training to optimise recruitment and the design of a future definitive trial.Setting Three specialist paediatric surgery centres in the UK.Patients Children (aged 4–15 years) with a clinical diagnosis of uncomplicated acute appendicitis.Interventions Appendicectomy or a non-operative treatment pathway (comprising broad-spectrum antibiotics and active observation).Main outcome measures Primary outcome measure was the proportion of eligible patients recruited. Secondary outcomes evaluated adherence to interventions, data collection during follow-up, safety of treatment pathways and clinical course.Results Fifty per cent of eligible participants (95% CI 40 to 59) approached about the trial agreed to participate and were randomised. Repeated bespoke recruiter training was associated with an increase in recruitment rate over the course of the trial from 38% to 72%. There was high acceptance of randomisation, good patient and surgeon adherence to trial procedures and satisfactory completion of follow-up. Although more participants had perforated appendicitis than had been anticipated, treatment pathways were found to be safe and adverse event profiles acceptable.Conclusion Recruitment to a randomised controlled trial examining the effectiveness and cost-effectiveness of a non-operative treatment pathway compared with appendicectomy for the treatment of uncomplicated acute appendicitis in children is feasible.Trial registration number ISRCTN15830435

Accurate and Rapid Identification of the Burkholderia pseudomallei Near-Neighbour, Burkholderia ubonensis, Using Real-Time PCR

Burkholderia ubonensis is an environmental bacterium belonging to the Burkholderia cepacia complex (Bcc), a group of genetically related organisms that are associated with opportunistic but generally nonfatal infections in healthy individuals. In contrast, the near-neighbour species Burkholderia pseudomallei causes melioidosis, a disease that can be fatal in up to 95% of cases if left untreated. B. ubonensis is frequently misidentified as B. pseudomallei from soil samples using selective culturing on Ashdown’s medium, reflecting both the shared environmental niche and morphological similarities of these species. Additionally, B. ubonensis shows potential as an important biocontrol agent in B. pseudomallei-endemic regions as certain strains possess antagonistic properties towards B. pseudomallei. Current methods for characterising B. ubonensis are laborious, time-consuming and costly, and as such this bacterium remains poorly studied. The aim of our study was to develop a rapid and inexpensive real-time PCR-based assay specific for B. ubonensis. We demonstrate that a novel B. ubonensis-specific assay, Bu550, accurately differentiates B. ubonensis from B. pseudomallei and other species that grow on selective Ashdown’s agar. We anticipate that Bu550 will catalyse research on B. ubonensis by enabling rapid identification of this organism from Ashdown’s-positive colonies that are not B. pseudomallei

Conservative treatment for uncomplicated appendicitis in children:the CONTRACT feasibility study, including feasibility RCT

Background Whilst non-operative treatment is known to be effective for the treatment of uncomplicated acute appendicitis in children, comparative randomised trial data reporting important outcomes compared to appendicectomy are lacking.ObjectivesTo ascertain the feasibility of conducting a multi-centre randomised controlled trial (RCT) testing the effectiveness and cost-effectiveness of a non-operative treatment pathway compared to appendicectomy for the treatment of uncomplicated acute appendicitis in children.•DesignMixed methods study including: a feasibility RCT; embedded and parallel qualitative and survey studies; parallel health economic feasibility study; development of a core outcome set.Setting Three specialist NHS Paediatric Surgical Units in EnglandParticipants Children (aged 4-15 years) clinically diagnosed with uncomplicated acute appendicitis participated in the feasibility RCT. Children, their families, recruiting clinicians and other healthcare professionals involved in caring for children with appendicitis took part in the qualitative study. UK Specialist Paediatric Surgeons took part in the survey. Specialist Paediatric Surgeons, Adult General Surgeons who treat children, and children and young people who previously had appendicitis along with their families took part in the core outcomes set development.Interventions Participants in the feasibility RCT were randomised to a non-operative treatment pathway (broad-spectrum antibiotics and active observation) or appendicectomy.Main outcome measures Primary outcome measure was the proportion of eligible patients recruited to the feasibility trial.Data sourcesNHS casenotes, questionnaire responses, transcribed audio recordings of recruitment discussions and qualitative interviewsResults Overall, 50% (95%CI 40-59) of 115 eligible participants approached about the trial agreed to participate and were randomised. There was high acceptance of randomisation and good adherence to trial procedures and follow-up (follow rates of 89%, 85% and 85% at six weeks, three months and six months respectively). More participants had perforated appendicitis than had been anticipated.Qualitative work enabled us to: communicate about the trial effectively with patients and families; design and deliver bespoke training to optimise recruitment; and understand how to optimise design and delivery of a future trial.The health economic study, indicated that the main cost drivers are the ward stay cost and the cost of the operation, and has informed quality of life assessment methods for future work.A core outcome set for the treatment of uncomplicated acute appendicitis in children and young people was developed, containing 14 outcomes.There is adequate surgeon interest to justify proceeding to an effectiveness trial with 51% of those surveyed expressing a willingness to recruit with an unchanged trial protocol.LimitationsSince the feasibility RCT was only performed in three centres we cannot guarantee successful recruitment across a larger number of sites. However, our qualitative work has informed a bespoke training package to facilitate this. Although survey results suggest adequate clinician interest to make a larger trial possible, actual participation may differ, and equipoise may have moved over time.Conclusions A future effectiveness trial is feasible following limited additional preparation to establish appropriate outcome measures and case identification. We recommend a limited package of qualitative work be included to optimise recruitment at new centres in particular.Future work Prior to proceeding to an effectiveness trial we need to: develop a robust method for distinguishing children with uncomplicated acute appendicitis from those with more advanced appendicitis; reach agreement on a primary outcome measure and effect size that is acceptable to all stakeholder groups involved.Study registration ISRCTN15830435.Funding detailsNIHR HTA programm

Development of a core outcome set to determine the overall treatment success of acute uncomplicated appendicitis in children: a study protocol

INTRODUCTION: In recent years, there has been growing interest in alternatives to appendicectomy. In particular, non-operative treatment of appendicitis, with antibiotics alone, has been proposed as a potential treatment. A small number of randomised controlled trials (RCTs) in adults and, more recently, children suggest that antibiotic treatment may be a valid alternative to appendicectomy. However, there is currently insufficient data to justify its widespread use. Prior to performing further efficacy studies of the treatment of appendicitis in children, it is imperative to identify the most relevant outcome measures for inclusion in the design of comparative studies. This is of particular importance when evaluating a novel treatment approach since the outcomes of importance may differ from those commonly reported with traditional therapies. A review of the relevant literature and electronic resources failed to identify a core outcome set (COS) for children with appendicitis. We aim to define a COS for the measurement of treatment interventions in children (<18 years) with acute appendicitis. METHODS AND ANALYSIS: This project will entail: (1) a systematic review to identify previously reported acute uncomplicated appendicitis treatment outcomes; (2) assembly of stakeholder panels (paediatric and adult surgeons, patients and parents); (3) a three-stage Delphi process; and (4) a final consensus meeting to complete the COS. ETHICS AND REGISTRATION: COS development is part of CONservative TReatment of Appendicitis in Children - a randomised controlled Trial (Feasibility) (CONTRACT) study, for which full ethical approval for CONTRACT has been granted. The COS development study is registered with the COMET Initiative in May 2017 (http://www.comet-initiative.org/studies/details/987)

The Sloan Digital Sky Survey Quasar Lens Search. III. Constraints on Dark Energy from the Third Data Release Quasar Lens Catalog

We present cosmological results from the statistics of lensed quasars in the Sloan Digital Sky Survey (SDSS) Quasar Lens Search. By taking proper account of the selection function, we compute the expected number of quasars lensed by early-type galaxies and their image separation distribution assuming a flat universe, which is then compared with 7 lenses found in the SDSS Data Release 3 to derive constraints on dark energy under strictly controlled criteria. For a cosmological constant model (w=-1) we obtain \Omega_\Lambda=0.74^{+0.11}_{-0.15}(stat.)^{+0.13}_{-0.06}(syst.). Allowing w to be a free parameter we find \Omega_M=0.26^{+0.07}_{-0.06}(stat.)^{+0.03}_{-0.05}(syst.) and w=-1.1\pm0.6(stat.)^{+0.3}_{-0.5}(syst.) when combined with the constraint from the measurement of baryon acoustic oscillations in the SDSS luminous red galaxy sample. Our results are in good agreement with earlier lensing constraints obtained using radio lenses, and provide additional confirmation of the presence of dark energy consistent with a cosmological constant, derived independently of type Ia supernovae.Comment: 9 pages, 3 figures, 2 tables, accepted for publication in A