17 research outputs found

    Adjunctive rifampicin for Staphylococcus aureus bacteraemia (ARREST): a multicentre, randomised, double-blind, placebo-controlled trial.

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    BACKGROUND: Staphylococcus aureus bacteraemia is a common cause of severe community-acquired and hospital-acquired infection worldwide. We tested the hypothesis that adjunctive rifampicin would reduce bacteriologically confirmed treatment failure or disease recurrence, or death, by enhancing early S aureus killing, sterilising infected foci and blood faster, and reducing risks of dissemination and metastatic infection. METHODS: In this multicentre, randomised, double-blind, placebo-controlled trial, adults (≥18 years) with S aureus bacteraemia who had received ≤96 h of active antibiotic therapy were recruited from 29 UK hospitals. Patients were randomly assigned (1:1) via a computer-generated sequential randomisation list to receive 2 weeks of adjunctive rifampicin (600 mg or 900 mg per day according to weight, oral or intravenous) versus identical placebo, together with standard antibiotic therapy. Randomisation was stratified by centre. Patients, investigators, and those caring for the patients were masked to group allocation. The primary outcome was time to bacteriologically confirmed treatment failure or disease recurrence, or death (all-cause), from randomisation to 12 weeks, adjudicated by an independent review committee masked to the treatment. Analysis was intention to treat. This trial was registered, number ISRCTN37666216, and is closed to new participants. FINDINGS: Between Dec 10, 2012, and Oct 25, 2016, 758 eligible participants were randomly assigned: 370 to rifampicin and 388 to placebo. 485 (64%) participants had community-acquired S aureus infections, and 132 (17%) had nosocomial S aureus infections. 47 (6%) had meticillin-resistant infections. 301 (40%) participants had an initial deep infection focus. Standard antibiotics were given for 29 (IQR 18-45) days; 619 (82%) participants received flucloxacillin. By week 12, 62 (17%) of participants who received rifampicin versus 71 (18%) who received placebo experienced treatment failure or disease recurrence, or died (absolute risk difference -1·4%, 95% CI -7·0 to 4·3; hazard ratio 0·96, 0·68-1·35, p=0·81). From randomisation to 12 weeks, no evidence of differences in serious (p=0·17) or grade 3-4 (p=0·36) adverse events were observed; however, 63 (17%) participants in the rifampicin group versus 39 (10%) in the placebo group had antibiotic or trial drug-modifying adverse events (p=0·004), and 24 (6%) versus six (2%) had drug interactions (p=0·0005). INTERPRETATION: Adjunctive rifampicin provided no overall benefit over standard antibiotic therapy in adults with S aureus bacteraemia. FUNDING: UK National Institute for Health Research Health Technology Assessment

    Comparing Efficacy of Epoxy Versus Cement for Outplanting Caribbean Staghorn Coral, Acropora cervicornis

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    Acropora cervicornis population declines since the 1970s initiated its listing as threatened under the US Endangered Species Act and critically endangered under the IUCN Red List. In response, restoration by outplanting nursery-reared A. cervicornis fragments to degraded reefs was developed. Here we compare outplanting A. cervicornis fragments using marine epoxy to a 10:1 cement/silica mix in clusters of six fragments across two sites off southeast Florida, USA. The epoxied outplants were established in December 2019 (n=810 fragments) and the cemented outplants were established in December 2020 (n=516 fragments). Outplant survival, attachment, and predation and disease prevalence was tracked for one year. Additionally, the effort associated with outplanting using each method was compared. After one year, the survival rate for the epoxied and cement fragments was 66% and 95%, respectively. Missing fragment prevalence for epoxied and cemented fragments was 24% an

    SFOMC: A Successful Navy And Academic Partnership Providing Sustained Ocean Observation Capabilities in the Florida Straits

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    To succeed at developing a nationwide Integrated Ocean Observing System (IOOS), stakeholders in academia, government, and industry must forge and maintain strategic partnerships. The South Florida Ocean Measurement Center (SFOMC) is such a partnership model and mutually beneficial collaboration that is conducting year-in and year-out major at-sea operations, sustaining the operation of a complex array of sub sea sensors, and providing the maintenance and the shore-based infrastructure to support both.The transformation of a longstanding, narrowly focused, and somewhat antiquated (but highly capable) Navy test and evaluation facility is described. Formerly plagued with a decreasing customer base and increasing operational costs, the Center\u27s transformation into this now fully integrated coalition has mitigated these forerunners of extinction while answering both Navy and academic needs. The successful partnership has resulted in modern facilities, a broad customer base, and steadily decreasing costs of operation. Examples are provided that demonstrate the ability of the Navy\u27s South Florida Testing Facility (SFTF) to realize user cost savings and to aid in the convergence of interest and capabilities among a variety of user groups toward the solution of problems of national concern, including naval research, homeland security, and environmental stewardship

    An Integrative Computational Approach for Prioritization of Genomic Variants

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    <div><p>An essential step in the discovery of molecular mechanisms contributing to disease phenotypes and efficient experimental planning is the development of weighted hypotheses that estimate the functional effects of sequence variants discovered by high-throughput genomics. With the increasing specialization of the bioinformatics resources, creating analytical workflows that seamlessly integrate data and bioinformatics tools developed by multiple groups becomes inevitable. Here we present a case study of a use of the distributed analytical environment integrating four complementary specialized resources, namely the Lynx platform, VISTA RViewer, the Developmental Brain Disorders Database (DBDB), and the RaptorX server, for the identification of high-confidence candidate genes contributing to pathogenesis of spina bifida. The analysis resulted in prediction and validation of deleterious mutations in the SLC19A placental transporter in mothers of the affected children that causes narrowing of the outlet channel and therefore leads to the reduced folate permeation rate. The described approach also enabled correct identification of several genes, previously shown to contribute to pathogenesis of spina bifida, and suggestion of additional genes for experimental validations. The study demonstrates that the seamless integration of bioinformatics resources enables fast and efficient prioritization and characterization of genomic factors and molecular networks contributing to the phenotypes of interest.</p></div
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