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Objective: To describe the epidemiology of sepsis in critical care by applying the Sepsis-3 criteria to electronic health records. Design: Retrospective cohort study using electronic health records. Setting: Ten intensive care units (ICU) from four United Kingdom National Health Service hospital trusts contributing to the National Institute for Health Research Critical Care Health Informatics Collaborative (CC-HIC).Patients: 28,456 critical care admissions (14,332 emergency medical, 4,585 emergency surgical, and 9,539 elective surgical)Measurements and Main Results: 29,343 episodes of clinical deterioration were identified with a rise in Sequential Organ Failure Assessment (SOFA) score of at least 2 points, of which 14,869 (50.7%) were associated with antibiotic escalation and thereby met the Sepsis-3 criteria for sepsis. 4,100 episodes of sepsis (27.6%) were associated with vasopressor use and lactate > 2.0 mmol/l, and therefore met the Sepsis-3 criteria for septic shock. ICU mortality by source of sepsis was highest for ICU-acquired sepsis (23.7%, 95% CI 21.9%, 25.6%), followed by hospital-acquired sepsis (18.6%, 95% CI 17.5%, 19.9%), and community-acquired sepsis (12.9%, 95% CI 12.1%, 13.6%) (p for comparison

Machining of carbon fibre reinforced polymer (CFRP) is abrasive and causes significant tool wear. The effect of tool wear on static flexural strength is investigated, using edge trimming with uncoated carbide and chemical vapour deposition (CVD) diamond coated burr style tools. Edge rounding (ER) criteria along with flank wear are used to observe tool degradation with ER shown to preferentially wear allowing the tool to become cyclically sharper and duller, corresponding to fluctuating dynamometer readings, a novelty for CFRP machining. Areal surface metrics degraded for an uncoated tool due to changes in cutting mechanism, whilst for up to 16.2 m of linear traverse, the coated tool showed limited changes. Tool wear, caused by edge trimming 7.2 m of CFRP, using an uncoated carbide tool, provided a flexural strength reduction of up to 10.5 %, directly linking tool wear to reduced mechanical strength.

The work is available online at LJMU and also via ResearchGate (https://www.researchgate.net/profile/Simon-Ashworth-4), Purpose: To explore the evolution of Facility Management (FM) in the Building Information Modelling (BIM) process. The research aimed to establish Critical Success Factors (CSF) which help deliver successful BIM projects, and to present these in a ‘FM-BIM Mobilisation Framework’. Background: Inefficiencies, poor collaboration and a focus on short-term costs in the construction industry, combined with a lack of innovation and digital competency when ordering projects, have resulted in a failure to deliver assets which have sustainable outcomes over their whole-life. Methodology: A mixed methods concurrent convergent design, incorporating side-by-side narrative text analysis was adopted to merge qualitative/quantitative findings. Critical Success Themes (CST) from literature were then used to establish CSF through; 19 interviews with FM/BIM experts, and a questionnaire to gauge FM industry awareness of BIM (using UK and international inputs). The final merged CSF were incorporated into a framework. This was validated using a two-stage process with a focus group using some of the same FM/BIM experts. Key findings: 10 CSF Main-Themes (MT), with a 100 Sub-Themes (ST) were identified covering important digital skills, knowledge and competences people require to contribute to the BIM process. Clients and Facility Mangers (FMs) must engage early if the full benefits of BIM are to be realised in the operational phase. They must clearly define their information requirements to align with business processes, and collaborate with the delivery team to ensure information is captured/transferred into the relevant management systems. Originality/value: The comprehensive end-to-end framework combines FM and BIM CSF into one online interactive tool which provides a wealth of useful knowledge, sources, benefits and practical examples. Although based on the UK BIM Framework, the alignment with ‘ISO 19650’ ensures it will also benefit an international audience.

A 22 full factorial design of experiment is used to investigate the effects of two machining platforms (5-axis elevated gantry versus 6-axis articulated robotic system) and two cutting tool designs (burr versus herringbone) on surface metrics and flexural strength of a 14 ply T300 2x2 carbon fibre reinforced polymer.\ud \ud A range of areal metrics were considered to characterise the surface with Sal and Stdi best able to represent differences due to the choice of robotic system or overhead gantry. The robotic system produces coupons with flexural strengths up to 26% higher than the overhead gantry. The choice of tool has a less significant effect however machine-tool interactions do play a role in the flexural strength.\ud \ud Analysis using scanning electron microscopy shows that defects may be obscured by smeared matrix which may contribute to overall flexural strength differences.

Elizabethkingia meningoseptica is an infrequent colonizer of the respiratory tract; its pathogenicity is uncertain. In the context of a 22-month outbreak of E. meningoseptica acquisition affecting 30 patients in a London, UK, critical care unit (3% attack rate) we derived a measure of attributable morbidity and determined whether E. meningoseptica is an emerging nosocomial pathogen. We found monomicrobial E. meningoseptica acquisition (n = 13) to have an attributable morbidity rate of 54% (systemic inflammatory response syndrome >2, rising C-reactive protein, new radiographic changes), suggesting that E. meningoseptica is a pathogen. Epidemiologic and molecular evidence showed acquisition was water-source–associated in critical care but identified numerous other E. meningoseptica strains, indicating more widespread distribution than previously considered. Analysis of changes in gram-negative speciation rates across a wider London hospital network suggests this outbreak, and possibly other recently reported outbreaks, might reflect improved diagnostics and that E. meningoseptica thus is a pseudo-emerging pathogen.

Microglial activation has been linked with deficits in neuronal function and synaptic plasticity in Alzheimer’s disease (AD). The mitochondrial translocator protein (TSPO) is known to be upregulated in reactive microglia. Accurate visualization and quantification of microglial density by PET imaging using the TSPO tracer [11C]-R-PK11195 has been challenging due to the limitations of the ligand. In this study, we aimed to evaluate the new TSPO tracer [11C]PBR28 as a marker for microglial activation in the 5XFAD transgenic mouse model of AD. Dynamic PET scans were acquired following intravenous administration of [11C]PBR28 in 6 month old 5XFAD mice and in wild-type controls. Autoradiography with [3H]PBR28 was carried out in the same brains to further confirm the distribution of the radioligand. In addition, immunohistochemistry was performed on adjacent brain sections of the same mice to evaluate the co-localization of TSPO with microglia. PET imaging revealed that brain uptake of [11C]PBR28 in 5XFAD mice was increased compared with control mice. Moreover, binding of [3H]PBR28, measured by autoradiography, was enriched in cortical and hippocampal brain regions, coinciding with the positive staining of the microglial marker Iba-1 and amyloid deposits in the same areas. Furthermore, double-staining using antibodies against TSPO demonstrated co-localization of TSPO with microglia and not with astrocytes in 5XFAD mice and human post-mortem AD brains. Our data provide support of the suitability of [11C]PBR28 as a tool for in vivo monitoring of microglial activation and assessment of treatment response in future studies using animal models of AD.

SummaryThe role of immune activation in psychiatric disorders has attracted considerable attention over the past two decades, contributing to the rise of a new era for psychiatry. Microglia, the macrophages of the brain, are progressively becoming the main focus of the research in this field. In this Review, we assess the literature on microglia activation across different psychiatric disorders, including post-mortem and in-vivo studies in humans and experimental studies in animals. Although microglia activation has been noted in all types of psychiatric disorder, no association was seen with specific diagnostic categories. Furthermore, the findings from these studies highlight that not all psychiatric patients have microglial activation. Therefore, the cause of the neuroinflammation in these cohorts and its implications are unclear. We discuss psychosocial stress as one of the main factors determining microglial activation in patients with psychiatric disorders, and explore the relevance of these findings for future treatment strategies.