It could be a ‘Golden Goose’: a qualitative study of views in primary care on an emergency admission risk prediction tool prior to implementation

BACKGROUND: Rising demand for health care has prompted interest in new technologies to support a shift of care from hospital to community and primary care, which may require clinicians to undertake new working practices. A predictive risk stratification tool (Prism) was developed for use in primary care to estimate patients’ risk of an emergency hospital admission. As part of an evaluation of Prism, we aimed to understand what might be needed to bring Prism into effective use by exploring clinicians and practice managers’ attitudes and expectations about using it. We were informed by Normalisation Process Theory (NPT) which examines the work needed to bring an innovation into use. METHODS: We conducted 4 focus groups and 10 interviews with a total of 43 primary care doctors and colleagues from 32 general practices. All were recorded and transcribed. Analysis focussed in particular on the construct of ‘coherence’ within NPT, which examines how people understand an innovation and its purpose. RESULTS: Respondents were in agreement that Prism was a technological formalisation of existing practice, and that it would function as a support to clinical judgment, rather than replacing it. There was broad consensus about the role it might have in delivering new models of care based on active management, but there were doubts about the scope for making a difference to some patients and about whether Prism could identify at-risk patients not already known to the clinical team. Respondents did not expect using the tool to be onerous, but were concerned about the work which might follow in delivering care. Any potential value would not be of the tool in isolation, but would depend on the availability of support services. CONCLUSIONS: Policy imperatives and the pressure of rising demand meant respondents were open to trying out Prism, despite underlying uncertainty about what difference it could make. TRIAL REGISTRATION: Controlled Clinical Trials no. ISRCTN55538212

Molecular analysis of metastasis in a polyomavirus middle T mouse model: the role of osteopontin

INTRODUCTION: In order to study metastatic disease, we employed the use of two related polyomavirus middle T transgenic mouse tumor transplant models of mammary carcinoma (termed Met and Db) that display significant differences in metastatic potential. METHODS: Through suppression subtractive hybridization coupled to the microarray, we found osteopontin (OPN) to be a highly expressed gene in the tumors of the metastatic mouse model, and a lowly expressed gene in the tumors of the lowly metastatic mouse model. We further analyzed the role of OPN in this model by examining sense and antisense constructs using in vitro and in vivo methods. RESULTS: With in vivo metastasis assays, the antisense Met cells showed no metastatic tumor formation to the lungs of recipient mice, while wild-type Met cells, with higher levels of OPN, showed significant amounts of metastasis. The Db cells showed a significantly reduced metastasis rate in the in vivo metastasis assay as compared with the Met cells. Db cells with enforced overexpression of OPN showed elevated levels of OPN but did not demonstrate an increase in the rate of metastasis compared with the wild-type Db cells. CONCLUSIONS: We conclude that OPN is an essential regulator of the metastatic phenotype seen in polyomavirus middle T-induced mammary tumors. Yet OPN expression alone is not sufficient to cause metastasis. These data suggest a link between metastasis and phosphatidylinositol-3-kinase-mediated transcriptional upregulation of OPN, but additional phosphatidylinositol-3-kinase-regulated genes may be essential in precipitating the metastasis phenotype in the polyomavirus middle T model

The energy–diversity relationship of complex bacterial communities in Arctic deep-sea sediments

The availability of nutrients and energy is a main driver of biodiversity for plant and animal communities in terrestrial and marine ecosystems, but we are only beginning to understand whether and how energy–diversity relationships may be extended to complex natural bacterial communities. Here, we analyzed the link between phytodetritus input, diversity and activity of bacterial communities of the Siberian continental margin (37–3427 m water depth). Community structure and functions, such as enzymatic activity, oxygen consumption and carbon remineralization rates, were highly related to each other, and with energy availability. Bacterial richness substantially increased with increasing sediment pigment content, suggesting a positive energy–diversity relationship in oligotrophic regions. Richness leveled off, forming a plateau, when mesotrophic sites were included, suggesting that bacterial communities and other benthic fauna may be structured by similar mechanisms. Dominant bacterial taxa showed strong positive or negative relationships with phytodetritus input and allowed us to identify candidate bioindicator taxa. Contrasting responses of individual taxa to changes in phytodetritus input also suggest varying ecological strategies among bacterial groups along the energy gradient. Our results imply that environmental changes affecting primary productivity and particle export from the surface ocean will not only affect bacterial community structure but also bacterial functions in Arctic deep-sea sediment, and that sediment bacterial communities can record shifts in the whole ocean ecosystem functioning

Finding the Needles in the Metagenome Haystack

In the collective genomes (the metagenome) of the microorganisms inhabiting the Earth’s diverse environments is written the history of life on this planet. New molecular tools developed and used for the past 15 years by microbial ecologists are facilitating the extraction, cloning, screening, and sequencing of these genomes. This approach allows microbial ecologists to access and study the full range of microbial diversity, regardless of our ability to culture organisms, and provides an unprecedented access to the breadth of natural products that these genomes encode. However, there is no way that the mere collection of sequences, no matter how expansive, can provide full coverage of the complex world of microbial metagenomes within the foreseeable future. Furthermore, although it is possible to fish out highly informative and useful genes from the sea of gene diversity in the environment, this can be a highly tedious and inefficient procedure. Microbial ecologists must be clever in their pursuit of ecologically relevant, valuable, and niche-defining genomic information within the vast haystack of microbial diversity. In this report, we seek to describe advances and prospects that will help microbial ecologists glean more knowledge from investigations into metagenomes. These include technological advances in sequencing and cloning methodologies, as well as improvements in annotation and comparative sequence analysis. More significant, however, will be ways to focus in on various subsets of the metagenome that may be of particular relevance, either by limiting the target community under study or improving the focus or speed of screening procedures. Lastly, given the cost and infrastructure necessary for large metagenome projects, and the almost inexhaustible amount of data they can produce, trends toward broader use of metagenome data across the research community coupled with the needed investment in bioinformatics infrastructure devoted to metagenomics will no doubt further increase the value of metagenomic studies in various environments

Is the inflammasome a potential therapeutic target in renal disease?

The inflammasome is a large, multiprotein complex that drives proinflammatory cytokine production in response to infection and tissue injury. Pattern recognition receptors that are either membrane bound or cytoplasmic trigger inflammasome assembly. These receptors sense danger signals including damage-associated molecular patterns and pathogen-associated molecular patterns (DAMPS and PAMPS respectively). The best-characterized inflammasome is the NLRP3 inflammasome. On assembly of the NLRP3 inflammasome, post-translational processing and secretion of pro-inflammatory cytokines IL-1β and IL-18 occurs; in addition, cell death may be mediated via caspase-1. Intrinsic renal cells express components of the inflammasome pathway. This is most prominent in tubular epithelial cells and, to a lesser degree, in glomeruli. Several primary renal diseases and systemic diseases affecting the kidney are associated with NLRP3 inflammasome/IL-1β/IL-18 axis activation. Most of the disorders studied have been acute inflammatory diseases. The disease spectrum includes ureteric obstruction, ischaemia reperfusion injury, glomerulonephritis, sepsis, hypoxia, glycerol-induced renal failure, and crystal nephropathy. In addition to mediating renal disease, the IL-1/ IL-18 axis may also be responsible for development of CKD itself and its related complications, including vascular calcification and sepsis. Experimental models using genetic deletions and/or receptor antagonists/antiserum against the NLRP3 inflammasome pathway have shown decreased severity of disease. As such, the inflammasome is an attractive potential therapeutic target in a variety of renal diseases

Global patient outcomes after elective surgery: prospective cohort study in 27 low-, middle- and high-income countries.

BACKGROUND: As global initiatives increase patient access to surgical treatments, there remains a need to understand the adverse effects of surgery and define appropriate levels of perioperative care. METHODS: We designed a prospective international 7-day cohort study of outcomes following elective adult inpatient surgery in 27 countries. The primary outcome was in-hospital complications. Secondary outcomes were death following a complication (failure to rescue) and death in hospital. Process measures were admission to critical care immediately after surgery or to treat a complication and duration of hospital stay. A single definition of critical care was used for all countries. RESULTS: A total of 474 hospitals in 19 high-, 7 middle- and 1 low-income country were included in the primary analysis. Data included 44 814 patients with a median hospital stay of 4 (range 2-7) days. A total of 7508 patients (16.8%) developed one or more postoperative complication and 207 died (0.5%). The overall mortality among patients who developed complications was 2.8%. Mortality following complications ranged from 2.4% for pulmonary embolism to 43.9% for cardiac arrest. A total of 4360 (9.7%) patients were admitted to a critical care unit as routine immediately after surgery, of whom 2198 (50.4%) developed a complication, with 105 (2.4%) deaths. A total of 1233 patients (16.4%) were admitted to a critical care unit to treat complications, with 119 (9.7%) deaths. Despite lower baseline risk, outcomes were similar in low- and middle-income compared with high-income countries. CONCLUSIONS: Poor patient outcomes are common after inpatient surgery. Global initiatives to increase access to surgical treatments should also address the need for safe perioperative care. STUDY REGISTRATION: ISRCTN5181700

The James Webb Space Telescope Mission

Twenty-six years ago a small committee report, building on earlier studies, expounded a compelling and poetic vision for the future of astronomy, calling for an infrared-optimized space telescope with an aperture of at least $4m$. With the support of their governments in the US, Europe, and Canada, 20,000 people realized that vision as the $6.5m$ James Webb Space Telescope. A generation of astronomers will celebrate their accomplishments for the life of the mission, potentially as long as 20 years, and beyond. This report and the scientific discoveries that follow are extended thank-you notes to the 20,000 team members. The telescope is working perfectly, with much better image quality than expected. In this and accompanying papers, we give a brief history, describe the observatory, outline its objectives and current observing program, and discuss the inventions and people who made it possible. We cite detailed reports on the design and the measured performance on orbit.Comment: Accepted by PASP for the special issue on The James Webb Space Telescope Overview, 29 pages, 4 figure