Plant-associated symbiotic Burkholderia species lack hallmark strategies required in mammalian pathogenesis

Burkholderia is a diverse and dynamic genus, containing pathogenic species as well as species that form complex interactions with plants. Pathogenic strains, such as B. pseudomallei and B. mallei, can cause serious disease in mammals, while other Burkholderia strains are opportunistic pathogens, infecting humans or animals with a compromised immune system. Although some of the opportunistic Burkholderia pathogens are known to promote plant growth and even fix nitrogen, the risk of infection to infants, the elderly, and people who are immunocompromised has not only resulted in a restriction on their use, but has also limited the application of non-pathogenic, symbiotic species, several of which nodulate legume roots or have positive effects on plant growth. However, recent phylogenetic analyses have demonstrated that Burkholderia species separate into distinct lineages, suggesting the possibility for safe use of certain symbiotic species in agricultural contexts. A number of environmental strains that promote plant growth or degrade xenobiotics are also included in the symbiotic lineage. Many of these species have the potential to enhance agriculture in areas where fertilizers are not readily available and may serve in the future as inocula for crops growing in soils impacted by climate change. Here we address the pathogenic potential of several of the symbiotic Burkholderia strains using bioinformatics and functional tests. A series of infection experiments using Caenorhabditis elegans and HeLa cells, as well as genomic characterization of pathogenic loci, show that the risk of opportunistic infection by symbiotic strains such as B. tuberum is extremely low

Effective implementation of research into practice: an overview of systematic reviews of the health literature

<p>Abstract</p> <p>Background</p> <p>The gap between research findings and clinical practice is well documented and a range of interventions has been developed to increase the implementation of research into clinical practice.</p> <p>Findings</p> <p>A review of systematic reviews of the effectiveness of interventions designed to increase the use of research in clinical practice. A search for relevant systematic reviews was conducted of Medline and the Cochrane Database of Reviews 1998-2009. 13 systematic reviews containing 313 primary studies were included. Four strategy types are identified: audit and feedback; computerised decision support; opinion leaders; and multifaceted interventions. Nine of the reviews reported on multifaceted interventions. This review highlights the small effects of single interventions such as audit and feedback, computerised decision support and opinion leaders. Systematic reviews of multifaceted interventions claim an improvement in effectiveness over single interventions, with effect sizes ranging from small to moderate. This review found that a number of published systematic reviews fail to state whether the recommended practice change is based on the best available research evidence.</p> <p>Conclusions</p> <p>This overview of systematic reviews updates the body of knowledge relating to the effectiveness of key mechanisms for improving clinical practice and service development. Multifaceted interventions are more likely to improve practice than single interventions such as audit and feedback. This review identified a small literature focusing explicitly on getting research evidence into clinical practice. It emphasizes the importance of ensuring that primary studies and systematic reviews are precise about the extent to which the reported interventions focus on changing practice based on research evidence (as opposed to other information codified in guidelines and education materials).</p

A Comprehensive Patient-Derived Xenograft Collection Representing the Heterogeneity of Melanoma

Therapy of advanced melanoma is changing dramatically. Following mutational and biological subclassification of this heterogeneous cancer, several targeted and immune therapies were approved and increased survival significantly. To facilitate further advancements through pre-clinical in vivo modeling, we have established 459 patient-derived xenografts (PDX) and live tissue samples from 384 patients representing the full spectrum of clinical, therapeutic, mutational, and biological heterogeneity of melanoma. PDX have been characterized using targeted sequencing and protein arrays and are clinically annotated. This exhaustive live tissue resource includes PDX from 57 samples resistant to targeted therapy, 61 samples from responders and non-responders to immune checkpoint blockade, and 31 samples from brain metastasis. Uveal, mucosal, and acral subtypes are represented as well. We show examples of pre-clinical trials that highlight how the PDX collection can be used to develop and optimize precision therapies, biomarkers of response, and the targeting of rare genetic subgroups

Integrated ecological monitoring in Wales: the Glastir Monitoring and Evaluation Programme field survey

The Glastir Monitoring and Evaluation Programme (GMEP) ran from 2013 until 2016 and was probably the most comprehensive programme of ecological study ever undertaken at a national scale in Wales. The programme aimed to (1) set up an evaluation of the environmental effects of the Glastir agri-environment scheme and (2) quantify environmental status and trends across the wider countryside of Wales. The focus was on outcomes for climate change mitigation, biodiversity, soil and water quality, woodland expansion, and cultural landscapes. As such, GMEP included a large field-survey component, collecting data on a range of elements including vegetation, land cover and use, soils, freshwaters, birds, and insect pollinators from up to three-hundred 1 km survey squares throughout Wales. The field survey capitalised upon the UK Centre for Ecology & Hydrology (UKCEH) Countryside Survey of Great Britain, which has provided an extensive set of repeated, standardised ecological measurements since 1978. The design of both GMEP and the UKCEH Countryside Survey involved stratified-random sampling of squares from a 1 km grid, ensuring proportional representation from land classes with distinct climate, geology and physical geography. Data were collected from different land cover types and landscape features by trained professional surveyors, following standardised and published protocols. Thus, GMEP was designed so that surveys could be repeated at regular intervals to monitor the Welsh environment, including the impacts of agri-environment interventions. One such repeat survey is scheduled for 2021 under the Environment and Rural Affairs Monitoring & Modelling Programme (ERAMMP). Data from GMEP have been used to address many applied policy questions, but there is major potential for further analyses. The precise locations of data collection are not publicly available, largely for reasons of landowner confidentiality. However, the wide variety of available datasets can be (1) analysed at coarse spatial resolutions and (2) linked to each other based on square-level and plot-level identifiers, allowing exploration of relationships, trade-offs and synergies. This paper describes the key sets of raw data arising from the field survey at co-located sites (2013 to 2016). Data from each of these survey elements are available with the following digital object identifiers (DOIs): Landscape features (Maskell et al., 2020a–c), https://doi.org/10.5285/82c63533-529e-47b9-8e78-51b27028cc7f, https://doi.org/10.5285/9f8d9cc6-b552-4c8b-af09-e92743cdd3de, https://doi.org/10.5285/f481c6bf-5774-4df8-8776-c4d7bf059d40; Vegetation plots (Smart et al., 2020), https://doi.org/10.5285/71d3619c-4439-4c9e-84dc-3ca873d7f5cc; Topsoil physico-chemical properties (Robinson et al., 2019), https://doi.org/10.5285/0fa51dc6-1537-4ad6-9d06-e476c137ed09; Topsoil meso-fauna (Keith et al., 2019), https://doi.org/10.5285/1c5cf317-2f03-4fef-b060-9eccbb4d9c21; Topsoil particle size distribution (Lebron et al., 2020), https://doi.org/10.5285/d6c3cc3c-a7b7-48b2-9e61-d07454639656; Headwater stream quality metrics (Scarlett et al., 2020a), https://doi.org/10.5285/e305fa80-3d38-4576-beef-f6546fad5d45; Pond quality metrics (Scarlett et al., 2020b), https://doi.org/10.5285/687b38d3-2278-41a0-9317-2c7595d6b882; Insect pollinator and flower data (Botham et al., 2020), https://doi.org/10.5285/3c8f4e46-bf6c-4ea1-9340-571fede26ee8; and Bird counts (Siriwardena et al., 2020), https://doi.org/10.5285/31da0a94-62be-47b3-b76e-4bdef3037360

Bacteria-inducing legume nodules involved in the improvement of plant growth, health and nutrition

Bacteria-inducing legume nodules are known as rhizobia and belong to the class Alphaproteobacteria and Betaproteobacteria. They promote the growth and nutrition of their respective legume hosts through atmospheric nitrogen fixation which takes place in the nodules induced in their roots or stems. In addition, rhizobia have other plant growth-promoting mechanisms, mainly solubilization of phosphate and production of indoleacetic acid, ACC deaminase and siderophores. Some of these mechanisms have been reported for strains of rhizobia which are also able to promote the growth of several nonlegumes, such as cereals, oilseeds and vegetables. Less studied are the mechanisms that have the rhizobia to promote the plant health; however, these bacteria are able to exert biocontrol of some phytopathogens and to induce the plant resistance. In this chapter, we revised the available data about the ability of the legume nodule-inducing bacteria for improving the plant growth, health and nutrition of both legumes and nonlegumes. These data showed that rhizobia meet all the requirements of sustainable agriculture to be used as bio-inoculants allowing the total or partial replacement of chemicals used for fertilization or protection of crops

Procalcitonin Is Not a Reliable Biomarker of Bacterial Coinfection in People With Coronavirus Disease 2019 Undergoing Microbiological Investigation at the Time of Hospital Admission

Abstract Admission procalcitonin measurements and microbiology results were available for 1040 hospitalized adults with coronavirus disease 2019 (from 48 902 included in the International Severe Acute Respiratory and Emerging Infections Consortium World Health Organization Clinical Characterisation Protocol UK study). Although procalcitonin was higher in bacterial coinfection, this was neither clinically significant (median [IQR], 0.33 [0.11–1.70] ng/mL vs 0.24 [0.10–0.90] ng/mL) nor diagnostically useful (area under the receiver operating characteristic curve, 0.56 [95% confidence interval, .51–.60]).</jats:p

Implementation of corticosteroids in treating COVID-19 in the ISARIC WHO Clinical Characterisation Protocol UK:prospective observational cohort study

BACKGROUND: Dexamethasone was the first intervention proven to reduce mortality in patients with COVID-19 being treated in hospital. We aimed to evaluate the adoption of corticosteroids in the treatment of COVID-19 in the UK after the RECOVERY trial publication on June 16, 2020, and to identify discrepancies in care. METHODS: We did an audit of clinical implementation of corticosteroids in a prospective, observational, cohort study in 237 UK acute care hospitals between March 16, 2020, and April 14, 2021, restricted to patients aged 18 years or older with proven or high likelihood of COVID-19, who received supplementary oxygen. The primary outcome was administration of dexamethasone, prednisolone, hydrocortisone, or methylprednisolone. This study is registered with ISRCTN, ISRCTN66726260. FINDINGS: Between June 17, 2020, and April 14, 2021, 47 795 (75·2%) of 63 525 of patients on supplementary oxygen received corticosteroids, higher among patients requiring critical care than in those who received ward care (11 185 [86·6%] of 12 909 vs 36 415 [72·4%] of 50 278). Patients 50 years or older were significantly less likely to receive corticosteroids than those younger than 50 years (adjusted odds ratio 0·79 [95% CI 0·70–0·89], p=0·0001, for 70–79 years; 0·52 [0·46–0·58], p80 years), independent of patient demographics and illness severity. 84 (54·2%) of 155 pregnant women received corticosteroids. Rates of corticosteroid administration increased from 27·5% in the week before June 16, 2020, to 75–80% in January, 2021. INTERPRETATION: Implementation of corticosteroids into clinical practice in the UK for patients with COVID-19 has been successful, but not universal. Patients older than 70 years, independent of illness severity, chronic neurological disease, and dementia, were less likely to receive corticosteroids than those who were younger, as were pregnant women. This could reflect appropriate clinical decision making, but the possibility of inequitable access to life-saving care should be considered. FUNDING: UK National Institute for Health Research and UK Medical Research Council

Qualitative impact assessment of land management interventions on ecosystem services (‘QEIA’). Report-2: integrated assessment

This project assessed the impacts of 741 potential land management actions, suitable for agricultural land in England, on the Farming & Countryside Programme’s Environmental Objectives (and therefore Environment Act targets and climate commitments) through 53 relevant environmental and cultural service indicators. The project used a combination of expert opinion and rapid evidence reviews, which included 1000+ pages of evidence in 10 separate reports with reference to over 2400 published studies, and an Integrated Assessment comprising expert-derived qualitative impact scores. The project has ensured that ELM schemes are evidence-based, offer good value for money, and contribute to SoS priorities for farming

Qualitative Impact Assessment of Land Management Interventions on Ecosystem Services (“QEIA”). Report-1: Executive Summary: QEIA Evidence Review & Integrated Assessment

The focus of this project was to provide an expert-led, rapid qualitative assessment of land management interventions on Ecosystem Services (ES) proposed for inclusion in Environmental Land Management (ELM) schemes. This involved a review of the current evidence base for 741 land management actions on 33 Ecosystem Services and 53 Ecosystem Service indicators by ten teams involving 45 experts drawn from the independent research community in a consistent series of Evidence Reviews covering the broad topics of: • Air quality • Greenhouse gas emissions • Soils • Water management • Biodiversity: croplands • Biodiversity: improved grassland • Biodiversity: semi-natural habitats • Biodiversity: integrated systems-based actions • Carbon sequestration • Cultural services (including recreation, geodiversity and regulatory services). It should be noted that this piece of work is just one element of the wider underpinning work Defra has commissioned to support the development of the ELM schemes

Qualitative impact assessment of land management interventions on Ecosystem Services (‘QEIA’). Report-2: Integrated Assessment

The focus of this project was to provide an expert-led, rapid qualitative assessment of land management interventions on Ecosystem Services (ES) proposed for inclusion in Environmental Land Management (ELM) schemes. This involved a review of the current evidence base for 741 land management actions on 33 Ecosystem Services and 53 Ecosystem Service indicators by ten expert teams drawn from the independent research community in a consistent series of ten Evidence Reviews covering the broad topics of; • Air quality • Greenhouse gas emissions • Soils • Water management • Biodiversity: croplands • Biodiversity: improved grassland • Biodiversity: semi-natural habitats • Biodiversity: integrated systems-based actions • Carbon sequestration • Cultural services (including recreation, geodiversity and regulatory services) These reviews were undertaken rapidly at Defra’s request by ten teams involving 45 experts who together captured more than 2,400 individual sources of evidence. This was followed by the Integrated Assessment (IA) reported here to provide a more accessible summary of these evidence reviews with a focus on capturing the actions with the greatest potential magnitude of change for the intended ES, and their potential co-benefits and trade-offs for the other ES