738 research outputs found

    A Global lake ecological observatory network (GLEON) for synthesising high-frequency sensor data for validation of deterministic ecological models

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    A Global Lake Ecological Observatory Network (GLEON; www.gleon.org) has formed to provide a coordinated response to the need for scientific understanding of lake processes, utilising technological advances available from autonomous sensors. The organisation embraces a grassroots approach to engage researchers from varying disciplines, sites spanning geographic and ecological gradients, and novel sensor and cyberinfrastructure to synthesise high-frequency lake data at scales ranging from local to global. The high-frequency data provide a platform to rigorously validate processbased ecological models because model simulation time steps are better aligned with sensor measurements than with lower-frequency, manual samples. Two case studies from Trout Bog, Wisconsin, USA, and Lake Rotoehu, North Island, New Zealand, are presented to demonstrate that in the past, ecological model outputs (e.g., temperature, chlorophyll) have been relatively poorly validated based on a limited number of directly comparable measurements, both in time and space. The case studies demonstrate some of the difficulties of mapping sensor measurements directly to model state variable outputs as well as the opportunities to use deviations between sensor measurements and model simulations to better inform process understanding. Well-validated ecological models provide a mechanism to extrapolate high-frequency sensor data in space and time, thereby potentially creating a fully 3-dimensional simulation of key variables of interest

    Detection of the florfenicol resistance gene floR in Chryseobacterium isolates from rainbow trout. Exception to the general rule?

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    Bacteria from the family Flavobacteriaceae often show low susceptibility to antibiotics. With the exception of two Chryseobacterium spp. isolates that were positive for the florfenicol resistance gene floR, no clinical resistance genes were identified by microarray in 36 Flavobacteriaceae isolates from salmonid fish that could grow in ≥ 4 mg/L florfenicol. Whole genome sequence analysis of the floR positive isolates revealed the presence of a region that contained the antimicrobial resistance genes floR, a tet(X) tetracycline resistance gene, a streptothricin resistance gene and a chloramphenicol acetyltransferase gene. In silico analysis of 377 published genomes for Flavobacteriaceae isolates from a range of sources confirmed that well-characterised resistance gene cassettes were not widely distributed in bacteria from this group. Efflux pump-mediated decreased susceptibility to a range of antimicrobials was confirmed in both floR positive isolates using an efflux pump inhibitor (phenylalanine-arginine β-naphthylamide) assay. The floR isolates possessed putative virulence factors, including production of siderophores and haemolysins, and were mildly pathogenic in rainbow trout. Results support the suggestion that, despite the detection of floR, susceptibility to antimicrobials in Flavobacteriaceae is mostly mediated via intrinsic mechanisms rather than the horizontally acquired resistance genes more normally associated with Gram-negative bacterial pathogens such as Enterobacteriaceae

    Clinical trial protocol: PRednisolone in early diffuse cutaneous Systemic Sclerosis (PRedSS)

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    From SAGE Publishing via Jisc Publications RouterHistory: received 2020-05-08, accepted 2020-08-16, epub 2020-09-17Publication status: PublishedFunder: Versus Arthritis; FundRef: https://doi.org/10.13039/501100012041; Grant(s): 21021Background:: Many of the painful, disabling features of early diffuse cutaneous systemic sclerosis have an inflammatory component and are potentially treatable with corticosteroid therapy. These features include painful and itchy skin, fatigue and musculoskeletal involvement. Yet many clinicians are understandably reluctant to prescribe corticosteroids because of the concern that these are a risk factor for scleroderma renal crisis. The aim of PRedSS (PRednisolone in early diffuse cutaneous Systemic Sclerosis) is to evaluate the efficacy and safety of moderate dose prednisolone in patients with early diffuse cutaneous systemic sclerosis, specifically whether moderate dose prednisolone is (a) effective in terms of reducing pain and disability, and improving skin score and (b) safe, with particular reference to renal function. Methods:: PRedSS is a Phase II, multicentre, double-blind randomised controlled trial which aims to recruit 72 patients with early diffuse cutaneous systemic sclerosis. Patients are randomised to receive either prednisolone (dosage approximately 0.3 mg/kg) or placebo therapy for 6 months. The two co-primary outcome measures are the difference in mean Health Assessment Questionnaire Disability Index at 3 months and the difference in modified Rodnan skin score at 3 months. Secondary outcome measures include patient reported outcome measures of itch, hand function, anxiety and depression, and helplessness. Results:: Recruitment commenced in December 2017 and after a slow start (due to delays in opening centres) 25 patients have now been recruited. Conclusion:: PRedSS should help to answer the question as to whether clinicians should or should not prescribe prednisolone in early diffuse cutaneous systemic sclerosis

    An Early and Comprehensive Millimetre and Centimetre Wave and X-ray Study of SN 2011dh: a Non-Equipartition Blast Wave Expanding into a Massive Stellar Wind

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    Only a handful of supernovae (SNe) have been studied in multiwavelengths from the radio to X-rays, starting a few days after the explosion. The early detection and classification of the nearby Type IIb SN 2011dh/PTF 11eon in M51 provides a unique opportunity to conduct such observations. We present detailed data obtained at one of the youngest phase ever of a core-collapse SN (days 3–12 after the explosion) in the radio, millimetre and X-rays; when combined with optical data, this allows us to explore the early evolution of the SN blast wave and its surroundings. Our analysis shows that the expanding SN shock wave does not exhibit equipartition (ϵe/ϵB ∼ 1000), and is expanding into circumstellar material that is consistent with a density profile falling like R−2. Within modelling uncertainties we find an average velocity of the fast parts of the ejecta of 15 000 ± 1800 km s−1, contrary to previous analysis. This velocity places SN 2011dh in an intermediate blast wave regime between the previously defined compact and extended SN Type IIb subtypes. Our results highlight the importance of early (∼1 d) high-frequency observations of future events. Moreover, we show the importance of combined radio/X-ray observations for determining the microphysics ratio ϵe/ϵB

    Population pharmacokinetics of artesunate and dihydroartemisinin in pregnant and non-pregnant women with malaria

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    <p>Abstract</p> <p>Background</p> <p>The World Health Organization endorses the use of artemisinin-based combination therapy for treatment of acute uncomplicated falciparum malaria in the second and third trimesters of pregnancy. However, the effects of pregnancy on the pharmacokinetics of artemisinin derivatives, such as artesunate (AS), are poorly understood. In this analysis, the population pharmacokinetics of oral AS, and its active metabolite dihydroartemisinin (DHA), were studied in pregnant and non-pregnant women at the Kingasani Maternity Clinic in the DRC.</p> <p>Methods</p> <p>Data were obtained from 26 pregnant women in the second (22 - 26 weeks) or the third (32 - 36 weeks) trimester of pregnancy and from 25 non-pregnant female controls. All subjects received 200 mg AS. Plasma AS and DHA were measured using a validated LC-MS method. Estimates for pharmacokinetic and variability parameters were obtained through nonlinear mixed effects modelling.</p> <p>Results</p> <p>A simultaneous parent-metabolite model was developed consisting of mixed zero-order, lagged first-order absorption of AS, a one-compartment model for AS, and a one-compartment model for DHA. Complete conversion of AS to DHA was assumed. The model displayed satisfactory goodness-of-fit, stability, and predictive ability. Apparent clearance (CL/F) and volume of distribution (V/F) estimates, with 95% bootstrap confidence intervals, were as follows: 195 L (139-285 L) for AS V/F, 895 L/h (788-1045 L/h) for AS CL/F, 91.4 L (78.5-109 L) for DHA V/F, and 64.0 L/h (55.1-75.2 L/h) for DHA CL/F. The effect of pregnancy on DHA CL/F was determined to be significant, with a pregnancy-associated increase in DHA CL/F of 42.3% (19.7 - 72.3%).</p> <p>Conclusions</p> <p>In this analysis, pharmacokinetic modelling suggests that pregnant women have accelerated DHA clearance compared to non-pregnant women receiving orally administered AS. These findings, in conjunction with a previous non-compartmental analysis of the modelled data, provide further evidence that higher AS doses would be required to maintain similar DHA levels in pregnant women as achieved in non-pregnant controls.</p

    Establishing a marine monitoring programme to assess antibiotic resistance: a case study from the Gulf Cooperation Council (GCC) region

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    The World Health Organization considers antimicrobial resistance as one of the most pressing global issues which poses a fundamental threat to human health, development, and security. Due to demographic and environmental factors, the marine environment of the Gulf Cooperation Council (GCC) region may be particularly susceptible to the threat of antimicrobial resistance. However, there is currently little information on the presence of AMR in the GCC marine environment to inform the design of appropriate targeted surveillance activities. The objective of this study was to develop, implement and conduct a rapid regional baseline monitoring survey of the presence of AMR in the GCC marine environment, through the analysis of seawater collected from high-risk areas across four GCC states: (Bahrain, Oman, Kuwait, and the United Arab Emirates). 560 Escherichia coli strains were analysed as part of this monitoring programme between December 2018 and May 2019. Multi-drug resistance (resistance to three or more structural classes of antimicrobials) was observed in 32.5% of tested isolates. High levels of reduced susceptibility to ampicillin (29.6%), nalidixic acid (27.9%), tetracycline (27.5%), sulfamethoxazole (22.5%) and trimethoprim (22.5%) were observed. Reduced susceptibility to the high priority critically important antimicrobials: azithromycin (9.3%), ceftazidime (12.7%), cefotaxime (12.7%), ciprofloxacin (44.6%), gentamicin (2.7%) and tigecycline (0.5%), was also noted. A subset of 173 isolates was whole genome sequenced, and high carriage rates of qnrS1 (60/173) and bla CTX-M-15 (45/173) were observed, correlating with reduced susceptibility to the fluoroquinolones and third generation cephalosporins, respectively. This study is important because of the resistance patterns observed, the demonstrated utility in applying genomic-based approaches to routine microbiological monitoring, and the overall establishment of a transnational AMR surveillance framework focussed on coastal and marine environments

    An Early & Comprehensive Millimeter and Centimeter Wave and X-ray Study of Supernova 2011dh: A Non-Equipartition Blastwave Expanding into A Massive Stellar Wind

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    Only a handful of supernovae (SNe) have been studied in multi-wavelength from radio to X-rays, starting a few days after explosion. The early detection and classification of the nearby type IIb SN2011dh/PTF11eon in M51 provides a unique opportunity to conduct such observations. We present detailed data obtained at the youngest phase ever of a core-collapse supernova (days 3 to 12 after explosion) in the radio, millimeter and X-rays; when combined with optical data, this allows us to explore the early evolution of the SN blast wave and its surroundings. Our analysis shows that the expanding supernova shockwave does not exhibit equipartition (e_e/e_B ~ 1000), and is expanding into circumstellar material that is consistent with a density profile falling like R^-2. Within modeling uncertainties we find an average velocity of the fast parts of the ejecta of 15,000 +/- 1800 km/s, contrary to previous analysis. This velocity places SN 2011dh in an intermediate blast-wave regime between the previously defined compact and extended SN IIb subtypes. Our results highlight the importance of early (~ 1 day) high-frequency observations of future events. Moreover, we show the importance of combined radio/X-ray observations for determining the microphysics ratio e_e/e_B.Comment: 9 pages, 5 figures, submitted to Ap

    Tissue sampling methods and standards for vertebrate genomics

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    The recent rise in speed and efficiency of new sequencing technologies have facilitated high-throughput sequencing, assembly and analyses of genomes, advancing ongoing efforts to analyze genetic sequences across major vertebrate groups. Standardized procedures in acquiring high quality DNA and RNA and establishing cell lines from target species will facilitate these initiatives. We provide a legal and methodological guide according to four standards of acquiring and storing tissue for the Genome 10K Project and similar initiatives as follows: four-star (banked tissue/cell cultures, RNA from multiple types of tissue for transcriptomes, and sufficient flash-frozen tissue for 1 mg of DNA, all from a single individual); three-star (RNA as above and frozen tissue for 1 mg of DNA); two-star (frozen tissue for at least 700 μg of DNA); and one-star (ethanol-preserved tissue for 700 μg of DNA or less of mixed quality). At a minimum, all tissues collected for the Genome 10K and other genomic projects should consider each species’ natural history and follow institutional and legal requirements. Associated documentation should detail as much information as possible about provenance to ensure representative sampling and subsequent sequencing. Hopefully, the procedures outlined here will not only encourage success in the Genome 10K Project but also inspire the adaptation of standards by other genomic projects, including those involving other biota
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