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Objective The purpose of this exploratory review c, including vitamin D, zinc, vitamin A, elderberry (S nigra), garlic (A sativum), licorice (G glabra), stinging nettle (U dioica), N-acetylcysteine, quercetin and selenium as potential adjunct therapies for the treatment of coronavirus infections. Methods A search of PubMed was performed for articles published from 2005 to 2021. Key words searched were zinc, vitamin A, vitamin D, Sambucus nigra, Allium sativum, Glycyrrhiza glabra, Urtica dioica, N-Acetylcysteine, quercetin, selenium and coronavirus. Results There were 47 articles selected for this review. Findings included that vitamin D, zinc, vitamin A, S nigra, A sativum, G glabra, U dioica, N-acetylcysteine, quercetin and selenium have been shown to produce anti-inflammatory, immunostimulatory or antiviral effects that may enhance the actions of standard therapeutics for the treatment of CoV infections. We found only research articles related to the effects of vitamin D, zinc, G glabra, quercetin and selenium against COVID-19. Conclusion We identified non-pharmaceutical supplements (Vitamin D, zinc, vitamin A, S nigra, A sativum, G glabra and U dioica) which may have potential to provide support for those with coronavirus infections. However, rigorous clinical studies need to be performed before any clinical recommendations can be made at this time.

Francisella tularensisis one of several biothreat agents for which a licensed vaccine is needed to protect against this pathogen. To aid in the development of a vaccine protective against pneumonic tularemia, we generated and characterized a panel ofF. tularensisisolates that can be used as challenge strains to assess vaccine efficacy. Our panel consists of both historical and contemporary isolates derived from clinical and environmental sources, including human, tick, and rabbit isolates. Whole genome sequencing was performed to assess the genetic diversity in comparison to the reference genomeF. tularensisSchu S4. Average nucleotide identity analysis showed >99% genomic similarity across the strains in our panel, and pan-genome analysis revealed a core genome of 1,707 genes, and an accessory genome of 233 genes. Three of the strains in our panel, FRAN254 (tick-derived), FRAN255 (a type B strain), and FRAN256 (a human isolate) exhibited variation from the other strains. Moreover, we identified several unique mutations within theFrancisellaPathogenicity Island across multiple strains in our panel, revealing unexpected diversity in this region. Notably, FRAN031 (Scherm) completely lacked the second pathogenicity island but retained virulence in mice. In contrast, FRAN037 (Coll) was attenuated in a murine pneumonic tularemia model and had mutations inpdpBandiglAwhich likely led to attenuation. All of the strains, except FRAN037, retained full virulence, indicating their effectiveness as challenge strains for future vaccine testing. Overall, we provide a well-characterized panel of virulentF. tularensisstrains that can be utilized in ongoing efforts to develop an effective vaccine against pneumonic tularemia to ensure protection is achieved across a rangeF. tularensisstrains.

Purpose. Burkholderia pseudomallei , the tier 1 agent of melioidosis, is a saprophytic microbe that causes endemic infections in tropical regions such as South-East Asia and Northern Australia. It is globally distributed, challenging to diagnose and treat, infectious by several routes including inhalation, and has potential for adversarial use. B. pseudomallei strain MSHR5848 produces two colony variants, smooth (S) and rough (R), which exhibit a divergent range of morphological, biochemical and metabolic phenotypes, and differ in macrophage and animal infectivity. We aimed to characterize two major phenotypic differences, analyse gene expression and study the regulatory basis of the variation. Methodology. Phenotypic expression was characterized by DNA and RNA sequencing, microscopy, and differential bacteriology. Regulatory genes were identified by cloning and bioinformatics. Results/Key findings. Whereas S produced larger quantities of extracellular DNA, R was upregulated in the production of a unique chromosome 1-encoded Siphoviridae-like bacteriophage, φMSHR5848. Exploratory transcriptional analyses revealed significant differences in variant expression of genes encoding siderophores, pili assembly, type VI secretion system cluster 4 (T6SS-4) proteins, several exopolysaccharides and secondary metabolites. A single 3 base duplication in S was the only difference that separated the variants genetically. It occurred upstream of a cluster of bacteriophage-associated genes on chromosome 2 that were upregulated in S. The first two genes were involved in regulating expression of the multiple phenotypes distinguishing S and R. Conclusion. Bacteriophage-associated proteins have a major role in the phenotypic expression of MSHR5848. The goals are to determine the regulatory basis of this phenotypic variation and its role in pathogenesis and environmental persistence of B. pseudomallei .

In offshore ultra-deepwater oil fields, weight and cost reduction is one of the operators’ top priorities, while maintaining safety and reliability standards. These challenges have made conventional flexible risers a less favourable choice for new construction and replacement projects and have forced asset owners to explore cost saving through innovative technologies such as Thermoplastic Composite Pipe (TCP). Magma Global’s light weight m-pipe® TCP riser and flowline product offers over 40% reduction in installed riser project costs, while bringing exceptional permeation, corrosion, high-temperature and fatigue performance and most importantly long-term reusability benefits. This product is the subject of a thorough qualification program in agreement with the requirements of operators and independent verification agents (IVA) to demonstrate the product’s safety and reliability to asset owners and local regulatory bodies. This paper presents recent developments on the qualification campaign of m-pipe® TCP for riser applications, with a focus on combined pressure and bending tests designed to verify the pipe strength and stiffness. It addresses the product’s ability to withstand loading in the riser touch-down region of a Free Hanging Catenary (FHC). The qualification process of sample manufacture, rig setup, instrumentation & testing, design model development and validation is presented. Burst load cases and combined bend & burst load cases are tested on m-pipe® and results are compared against design model predictions. We hope the paper will be of interest to anyone working in new material development or product qualification in the offshore industry.

Summary Bundibugyo virus (BDBV) is one of four ebolaviruses known to cause disease in humans. Bundibugyo virus disease (BVD) outbreaks occurred in 2007–2008 in Bundibugyo District, Uganda, and in 2012 in Isiro, Province Orientale, Democratic Republic of the Congo. The 2012 BVD outbreak resulted in 38 laboratory-confirmed cases of human infection, 13 of whom died. However, only 4 BDBV specimens from the 2012 outbreak have been sequenced. Here, we provide BDBV sequences from seven additional patients. Analysis of the molecular epidemiology and evolutionary dynamics of the 2012 outbreak with these additional isolates challenges the current hypothesis that the outbreak was the result of a single spillover event. In addition, one patient record indicates that BDBV’s initial emergence in Isiro occurred 50 days earlier than previously accepted. Collectively, this work demonstrates how retrospective sequencing can be used to elucidate outbreak origins and provide epidemiological contexts to a medically relevant pathogen., Graphical abstract, Highlights In 2012, BDBV was circulating earlier than previously appreciated BDBV genomes from seven additional patients are sequenced Molecular analyses indicate that multiple spillover events fueled the BVD outbreak, Elucidation of the epidemiology underlying the 2012 Bundibugyo virus disease outbreak in the Democratic Republic of the Congo has been challenging. Hulseberg et al. acquire additional genomic and phylodynamic data indicating that multiple Bundibugyo virus spillover events, some of which occurred much earlier than previously known, contributed to the outbreak.

Subsea Pumping Well Intervention Systems (SPWISs) include a reeled fluid conduit (or riser) that connects a surface pumping spread to a subsea tree via a subsea safety module. Current pipe technologies used for fluid conduits are limited in terms of their pressure capability, volume of fluid they can supply, fatigue performance or the ease with which they can be deployed. Thermoplastic Composite Pipe (TCP) addresses many of the limitations of existing products, and therefore is attractive as an alternative. This paper describes the qualification of a TCP as a SPWIS fluid conduit. The TCP is manufactured from carbon and S2-glass fibre, laminated with a Poly Ether Etherketone (PEEK) matrix. The TCP was qualified following the processes recommended by DNV-RP-A203 "Qualification of New Technology" and the specific guidance given in DNVGL-RP-F119 "Recommended Practice for TCPs". The former defines a structured process for developing a qualification basis, assessing the risk of all potential product failure modes, and then mitigating those risks through the collection of qualification evidence. The latter provides a methodology based upon a testing pyramid and a linked structural model, to gather the appropriate qualification evidence for a TCP. The results of the TCP qualification are presented in three areas, materials testing, pipe testing and structural analysis. The material testing focussed on characterising both pure PEEK, and the properties of individual carbon and S2-glass plies in the composite laminate. Testing was performed across the design temperature range (4°C to 80°C), and was used as input into the structural model of the TCP that was developed. At a pipe scale a comprehensive set of single and combined static load cases were tested, including axial tension and compression, internal pressure, bending, and bending and internal pressure. These test results were compared against the predicted TCP performance given by the structural model, both in terms of stiffness and ultimate failure. In addition to the static testing, long term performance of the composite laminate was also characterised. Laminate testing methods were developed for fatigue and stress rupture, and the test results used to construct life curves for both failure modes. The combination of both the materials and pipe testing, and the structural analysis, culminated in a qualification certificate being issued for the TCP by an Independent Verification Agent. DNVGL-RP-F119 is a new recommended practice that was published in December 2015. This paper presents one of the first applications of the recommended practice to a TCP product, and therefore provides valuable insight into the practical implementation of DNVGL-RP-F119. In addition, qualification of a TCP as a SPWIS fluid conduit offers the potential to enable more frequent and effective well interventions, thereby improving the productivity and ultimately reducing the cost of subsea wells.

Background: Computerised decision support (CDS) based on trustworthy clinical guidelines is a key componentof a learning healthcare system. Research shows that the effectiveness of CDS is mixed.Multifaceted context, system, recommendation and implementation factors may potentially affect the success ofCDS interventions. This paper describes the development of a checklist that is intended to support professionals toimplement CDS successfully.Methods: We developed the checklist through an iterative process that involved a systematic review of evidenceand frameworks, a synthesis of the success factors identified in the review, feedback from an international expertpanel that evaluated the checklist in relation to a list of desirable framework attributes, consultations with patientsand healthcare consumers and pilot testing of the checklist.Results: We screened 5347 papers and selected 71 papers with relevant information on success factors forguideline-based CDS. From the selected papers, we developed a 16-factor checklist that is divided in four domains,i.e. the CDS context, content, system and implementation domains. The panel of experts evaluated the checklistpositively as an instrument that could support people implementing guideline-based CDS across a wide range ofsettings globally. Patients and healthcare consumers identified guideline-based CDS as an important qualityimprovement intervention and perceived the GUIDES checklist as a suitable and useful strategy.Conclusions: The GUIDES checklist can support professionals in considering the factors that affect the success ofCDS interventions. It may facilitate a deeper and more accurate understanding of the factors shaping CDSeffectiveness. Relying on a structured approach may prevent that important factors are missed.Keywords: Clinical computerised decision support systems, Practice Guidelines, Guideline adherence,Evidence-based medicine, Implementation

This article explores new process safety metrics for measuring process safety performance in the chemical processing industry. While Process Safety Management enables an operation to optimize their process safety programs and organizational risks, there is an emerging need to evaluate process safety implementation across an organization through measurement of key indicators. Lagging metrics utilize process safety incidents as the numerator and divide it by an appropriate process-related denominator or “normalization factor.” Currently, work hours is used extensively as a normalization factor to evaluate safety performance in the process industries. However, this lagging metric does not directly reflect process safety information and may not accurately reflect the safety performance of the process. Modified denominators are explored in this study and compared with the existing time-based denominator to validate the effectiveness and applicability of the new metrics. Each proposed normalization factor was validated using available industry data. A statistical unitization method has been used to convert incident rates of different ranges for the convenience of comparison. Results show that some proposed process-related metrics have potential as alternatives, used along with the time-based metric, to evaluate process safety performance within organizations. © 2013 American Institute of Chemical Engineers Process Saf Prog 32: 337–345, 2013

This case alerts readers to the occurrence of grammatical, nonsensical speech in a 14-year-old boy, an alarming symptom. Speech of this sort may be caused by serious medical conditions such as cerebral irritation and acute confusional states, but in this case it was most probably part of a sleepwalking episode associated with jetlag. Abnormal speech during sleepwalking has been described, but it is not well characterised. This report of somniloquy offers some descriptive phenomenology for such speech.

To investigate best practices for implementing and managing clinical decision support (CDS) in community hospitals and ambulatory settings, we carried out a series of ethnographic studies to gather information from nine diverse organizations. Using the Rapid Assessment Process methodology, we conducted surveys, interviews, and observations over a period of two years in eight different geographic regions of the U.S.A. We first utilized a template organizing method for an expedited analysis of the data, followed by a deeper and more time consuming interpretive approach. We identified five major categories of best practices that require careful consideration while carrying out the planning, implementation, and knowledge management processes related to CDS. As more health care organizations implement clinical systems such as computerized provider order entry with CDS, descriptions of lessons learned by CDS pioneers can provide valuable guidance so that CDS can have optimal impact on health care quality.

How does paper usage change following the introduction of Computerized Physician Order Entry and the Electronic Medical Record (EMR/CPOE)? To answer that question we analyzed data collected from fourteen sites across the U.S. We found paper in widespread use in all institutions we studied. Analysis revealed psychological, ergonomic, technological, and regulatory reasons for the persistence of paper in an electronic environment. Paper has unique attributes allowing it to fill gaps in information timeliness, availability, and reliability in pursuit of improved patient care. Creative uses have led to "better paper."

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