Prehospital recognition of sepsis by ambulance clinicians (PRoSAiC)

Context: Prehospital recognition of adult patients with sepsis may inform scene management by ambulance clinicians, improve decisions concerning both appropriate hospital destination and urgency of transport, as well as facilitate early intervention before arriving at hospital. Objective: To develop a prehospital sepsis screening tool, derived from prehospital data, for use by ambulance clinicians. Design: The thesis comprises a systematic review of sepsis among adult patients in the prehospital environment, followed by the derivation and validation of a sepsis screening tool, utilising a retrospective data cohort comprising data from West Midlands Ambulance Service (WMAS) and the Emergency Department at University Hospital North Staffordshire (UHNS). This is followed by a comparison with alternate screening tools. Patients: Consecutive patients transported by WMAS (n=38483) to UHNS between 01 July 2013 and 30 June 2014. Records were linked using LinkPlus® software. Successful linkage was achieved in 33289 cases (86%). Eligible patients included adult, non-trauma, non-mental health, non-cardiac arrest cases. Of 33289 linked cases, 22945 cases were eligible. The eligible cases were randomly divided into derivation (n=16063, 70%) and validation (n=6882, 30%) cohorts. Outcome Measure: High risk of sepsis, as defined by the 2016 National Institute for Health and Care Excellence (NICE) Sepsis guideline (NG51). Results: High risk of sepsis was present in 3.7% of both derivation (n=593) and validation (n=254) cohorts. The Screening to Enhance PrehoSpital Identification of Sepsis (SEPSIS) tool is composed of the following variables: age, respiratory rate, peripheral oxygen saturations, heart rate, systolic blood pressure, temperature and level of consciousness (p<0.001 for all variables). Area under the receiver operating characteristic curve was 0.87 (95%CI 0.85-0.88) for the derivation cohort, and 0.86 (95%CI 0.84-0.88) for the validation cohort. Applying a cut-off of 3 or higher, sensitivity for the SEPSIS screening tool was 0.80 (95%CI 0.74-0.84), specificity was 0.78 (95%CI 0.77-0.79), positive predictive value was 0.12 (95%CI 0.10-0.14), negative predictive value was 0.99 (95%CI 0.99-0.99), positive likelihood ratio was 3.56 (95%CI 3.30-3.85), negative likelihood ratio was 0.26 (95%CI 0.21-0.34) and the diagnostic odds ratio was 13.5 (95%CI 9.9-18.4). Conclusion: The SEPSIS screening tool was significantly associated with high risk of sepsis status on arrival at the Emergency Department. It performs marginally better than both the UK Sepsis Trust “Red Flag” algorithm and National Early Warning Score (NEWS≥5) in an undifferentiated, adult, medical population. The SEPSIS screening tool requires external validation, in clinical practice by ambulance clinicians, in an independent population

A synaptic nidogen: developmental regulation and role of nidogen-2 at the neuromuscular junction

Background: The skeletal neuromuscular junction is a useful model for elucidating mechanisms that regulate synaptogenesis. Developmentally important intercellular interactions at the neuromuscular junction are mediated by the synaptic portion of a basal lamina that completely ensheaths each muscle fiber. Basal laminas in general are composed of four main types of glycosylated proteins: laminins, collagens IV, heparan sulfate proteoglycans and nidogens (entactins). The portion of the muscle fiber basal lamina that passes between the motor nerve terminal and postsynaptic membrane has been shown to bear distinct isoforms of the first three of these. For laminins and collagens IV, the proteins are deposited by the muscle; a synaptic proteoglycan, z-agrin, is deposited by the nerve. In each case, the synaptic isoform plays key roles in organizing the neuromuscular junction. Here, we analyze the fourth family, composed of nidogen-1 and -2.Results: In adult muscle, nidogen-1 is present throughout muscle fiber basal lamina, while nidogen- 2 is concentrated at synapses. Nidogen-2 is initially present throughout muscle basal lamina, but is lost from extrasynaptic regions during the first three postnatal weeks. Neuromuscular junctions in mutant mice lacking nidogen-2 appear normal at birth, but become topologically abnormal as they mature. Synaptic laminins, collagens IV and heparan sulfate proteoglycans persist in the absence of nidogen-2, suggesting the phenotype is not secondary to a general defect in the integrity of synaptic basal lamina. Further genetic studies suggest that synaptic localization of each of the four families of synaptic basal lamina components is independent of the other three.Conclusion: All four core components of the basal lamina have synaptically enriched isoforms. Together, they form a highly specialized synaptic cleft material. Individually, they play distinct roles in the formation, maturation and maintenance of the neuromuscular junction

Scotland's Great War Memorials

An overview of the process and meaning behind the memorials to the fallen of the Great War erected across Scotland c.1918-c.1939: part of a special issue of this magazine on the Great War for the centenary of 1918

Impact of prehospital care on outcomes in sepsis : a systematic review

Introduction: Sepsis is a common and potentially life-threatening response to an infection. International treatment guidelines for sepsis advocate that treatment be initiated at the earliest possible opportunity. It is not yet clear if very early intervention by ambulance clinicians prior to arrival at hospital leads to improved clinical outcomes among sepsis patients. Methoda: We systematically searched the electronic databases MEDLINE, EMBASE, CINAHL, the Cochrane Library and PubMed up to June 2015. In addition, subject experts were contacted. We adopted the GRADE (grading recommendations assessment, development and evaluation) methodology to conduct the review and follow PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) recommendations to report findings. Results: Nine studies met the eligibility criteria – one study was a randomized controlled trial while the remaining studies were observational in nature. There was considerable variation in the methodological approaches adopted and outcome measures reported across the studies. Because of these differences, the studies did not answer a unique research question and meta-analysis was not appropriate. A narrative approach to data synthesis was adopted. Conclusion: There is little robust evidence addressing the impact of prehospital interventions on outcomes in sepsis. That which is available is of low quality and indicates that prehospital interventions have limited impact on outcomes in sepsis beyond improving process outcomes and expediting the patient’s passage through the emergency care pathway. Evidence indicating that prehospital antibiotic therapy and fluid resuscitation improve patient outcomes is currently lacking. [West J Emerg Med. 2017;17(4)427-437.

Comparing Check-All and Forced-Choice Question Formats in Web Surveys

For survey researchers, it is common practice to use the check-all question format in Web and mail surveys but to convert to the forced-choice question format in telephone surveys. The assumption underlying this practice is that respondents will answer the two formats similarly. In this research note we report results from 16 experimental comparisons in two Web surveys and a paper survey conducted in 2002 and 2003 that test whether the check-all and forced-choice formats produce similar results. In all 16 comparisons, we find that the two question formats do not perform similarly; respondents endorse more options and take longer to answer in the forced-choice format than in the check-all format. These findings suggest that the forced-choice question format encourages deeper processing of response options and, as such, is preferable to the check-all format, which may encourage a weak satisficing response strategy. Additional analyses show that neither acquiescence bias nor item nonresponse seem to pose substantial problems for use of the forced-choice question format in Web surveys

Reputations and national identity, or, what do our heroes say about us?

It seems appropriate to be writing this introduction in the same week as the new Dictionary of National Biography (ODNB) is launched and the Biographical Dictionary of Scottish Women celebrates the completion of the commissioning of its entries. Whatever scruples some historians may have over the worth or relevance of biography, there is no doubting its popularity; the tables and shelves of every bookshop groans under the weight of biographies and ghosted autobiographies of past and present f..

Reputations and national identity, or, what do our heroes say about us?

It seems appropriate to be writing this introduction in the same week as the new Dictionary of National Biography (ODNB) is launched and the Biographical Dictionary of Scottish Women celebrates the completion of the commissioning of its entries. Whatever scruples some historians may have over the worth or relevance of biography, there is no doubting its popularity; the tables and shelves of every bookshop groans under the weight of biographies and ghosted autobiographies of past and present f..

A multi-proxy provenance study of late carboniferous to middle Jurassic sandstones in the Eastern Sverdrup basin and its bearing on arctic palaeogeographic reconstructions

A multi-proxy provenance study of Late Carboniferous to Middle Jurassic sandstones from the eastern Sverdrup Basin was undertaken employing optical petrography and heavy mineral analysis, chemical analysis of apatite, garnet and rutile grains, as well as detrital zircon U–Pb geochronology and Hf isotope analysis. Late Carboniferous to Middle Jurassic strata on the southern basin margin are inferred as being predominantly reworked from Silurian to Devonian strata within the adjacent Franklinian Basin succession. Higher-grade metamorphic detritus appeared during Middle to Late Triassic times and indicates exhumation and erosion of lower (Neoproterozoic to Cambrian) levels within the Franklinian Basin succession and/or a direct detrital input from the Canadian-Greenland Shield

Vru (Sub0144) controls expression of proven and putative virulence determinants and alters the ability of Streptococcus uberis to cause disease in dairy cattle

The regulation and control of gene expression in response to differing environmental stimuli is crucial for successful pathogen adaptation and persistence. The regulatory gene vru of Streptococcus uberis encodes a stand-alone response regulator with similarity to the Mga of group A Streptococcus. Mga controls expression of a number of important virulence determinants. Experimental intramammary challenge of dairy cattle with a mutant of S. uberis carrying an inactivating lesion in vru showed reduced ability to colonize the mammary gland and an inability to induce clinical signs of mastitis compared with the wild-type strain. Analysis of transcriptional differences of gene expression in the mutant, determined by microarray analysis, identified a number of coding sequences with altered expression in the absence of Vru. These consisted of known and putative virulence determinants, including Lbp (Sub0145), SclB (Sub1095), PauA (Sub1785) and hasA (Sub1696)