Identifying which septic patients have increased mortality risk using severity scores:a cohort study

Background: Early aggressive therapy can reduce the mortality associated with severe sepsis but this relies on prompt recognition, which is hindered by variation among published severity criteria. Our aim was to test the performance of different severity scores in predicting mortality among a cohort of hospital inpatients with sepsis. Methods: We anonymously linked routine outcome data to a cohort of prospectively identified adult hospital inpatients with sepsis, and used logistic regression to identify associations between mortality and demographic variables, clinical factors including blood culture results, and six sets of severity criteria. We calculated performance characteristics, including area under receiver operating characteristic curves (AUROC), of each set of severity criteria in predicting mortality. Results: Overall mortality was 19.4% (124/640) at 30 days after sepsis onset. In adjusted analysis, older age (odds ratio 5.79 (95% CI 2.87-11.70) for ≥80y versus <60y), having been admitted as an emergency (OR 3.91 (1.31-11.70) versus electively), and longer inpatient stay prior to sepsis onset (OR 2.90 (1.41-5.94) for >21d versus <4d), were associated with increased 30 day mortality. Being in a surgical or orthopaedic, versus medical, ward was associated with lower mortality (OR 0.47 (0.27-0.81) and 0.26 (0.11-0.63), respectively). Blood culture results (positive vs. negative) were not significantly association with mortality. All severity scores predicted mortality but performance varied. The CURB65 community-acquired pneumonia severity score had the best performance characteristics (sensitivity 81%, specificity 52%, positive predictive value 29%, negative predictive value 92%, for 30 day mortality), including having the largest AUROC curve (0.72, 95% CI 0.67-0.77). Conclusions: The CURB65 pneumonia severity score outperformed five other severity scores in predicting risk of death among a cohort of hospital inpatients with sepsis. The utility of the CURB65 score for risk-stratifying patients with sepsis in clinical practice will depend on replicating these findings in a validation cohort including patients with sepsis on admission to hospital

Flash-lag chimeras: the role of perceived alignment in the composite face effect

Spatial alignment of different face halves results in a configuration that mars the recognition of the identity of either face half (). What would happen to the recognition performance for face halves that were aligned on the retina but were perceived as misaligned, or were misaligned on the retina but were perceived as aligned? We used the 'flash-lag' effect () to address these questions. We created chimeras consisting of a stationary top half-face initially aligned with a moving bottom half-face. Flash-lag chimeras were better recognized than their stationary counterparts. However when flashed face halves were presented physically ahead of moving halves thereby nulling the flash-lag effect, recognition was impaired. This counters the notion that relative movement between the two face halves per se is sufficient to explain better recognition of flash-lag chimeras. Thus, the perceived spatial alignment of face halves (despite retinal misalignment) impairs recognition, while perceived misalignment (despite retinal alignment) does not

The metabolism of anabolic-androgenic steroids in the greyhound

BACKGROUND Effective control of the use of anabolic-androgenic steroids (AASs) in animal sports is essential in order to ensure both animal welfare and integrity. In order to better police their use in Australian and New Zealand greyhound racing, thorough metabolic studies have been carried out on a range of registered human and veterinary AASs available in the region. RESULTS Canine metabolic data are presented for the AASs boldenone, danazol, ethylestrenol, mesterolone, methandriol, nandrolone and norethandrolone. The principal Phase I metabolic processes observed were the reduction of A-ring unsaturations and/or 3-ketones with either 3α,5β- or 3β,5α-stereochemistry, the oxidation of secondary 17β-hydroxyl groups and 16α-hydroxylation. The Phase II β-glucuronylation of sterol metabolites was extensive. CONCLUSION The presented data have enabled the effective analysis of AASs and their metabolites in competition greyhound urine samples.Australian Research Council LP077483

Management of multimorbidity using a patient-centred care model:a pragmatic cluster-randomised trial of the 3D approach

Background: The management of people with multiple chronic conditions challenges health-care systems designed around single conditions. There is international consensus that care for multimorbidity should be patient-centred, focus on quality of life, and promote self-management towards agreed goals. However, there is little evidence about the effectiveness of this approach. Our hypothesis was that the patient-centred, so-called 3D approach (based on dimensions of health, depression, and drugs) for patients with multimorbidity would improve their health-related quality of life, which is the ultimate aim of the 3D intervention. Methods: We did this pragmatic cluster-randomised trial in general practices in England and Scotland. Practices were randomly allocated to continue usual care (17 practices) or to provide 6-monthly comprehensive 3D reviews, incorporating patient-centred strategies that reflected international consensus on best care (16 practices). Randomisation was computer-generated, stratified by area, and minimised by practice deprivation and list size. Adults with three or more chronic conditions were recruited. The primary outcome was quality of life (assessed with EQ-5D-5L) after 15 months' follow-up. Participants were not masked to group assignment, but analysis of outcomes was blinded. We analysed the primary outcome in the intention-to-treat population, with missing data being multiply imputed. This trial is registered as an International Standard Randomised Controlled Trial, number ISRCTN06180958. Findings: Between May 20, 2015, and Dec 31, 2015, we recruited 1546 patients from 33 practices and randomly assigned them to receive the intervention (n=797) or usual care (n=749). In our intention-to-treat analysis, there was no difference between trial groups in the primary outcome of quality of life (adjusted difference in mean EQ-5D-5L 0·00, 95% CI −0·02 to 0·02; p=0·93). 78 patients died, and the deaths were not considered as related to the intervention. Interpretation: To our knowledge, this trial is the largest investigation of the international consensus about optimal management of multimorbidity. The 3D intervention did not improve patients' quality of life. Funding: National Institute for Health Research

Analysis of Photon Detection Efficiency and Dynamic Range in SPAD based Visible Light Receivers

We investigate the photon detection efficiency (PDE) and the dynamic range for digital silicon photomultipliers (dSiPMs) over a selection of design parameters: dSiPM unit cell dead time, PDE, unit cell area and fill factor, number of cells, and total dSiPM active area. Two receiver scaling scenarios are con-sidered: varying the number of cells for 1) a fixed unit cell area or 2) a fixed total dSiPM area. Theoretical and simulated results are confirmed with experimental data from a selection of dSiPMs realised on a test chip in130-nm CMOS process

A Simulation Model for Digital Silicon Photomultipliers

We propose a simulator model to estimate the performance of digital Silicon Photomultipliers (dSiPM) based on Single Photon Avalanche Diodes (SPADs) in terms of detection rate of photons incident on the sensor. The work provides guidelines for efficient array structure depending on: the number of SPADs, fill factor, area of both SPADs and array. A comparison of the main techniques present in the literature to digitally combine multiple outputs into single channel is included with simulated results showing promising higher detection rates for XOR-based dSiPMs. Mathematical expressions are derived to estimate dSiPM parameters such as maximum detection rate and detector dead time as functions of the mentioned design parameters

Primordialists and Constructionists: a typology of theories of religion

This article adopts categories from nationalism theory to classify theories of religion. Primordialist explanations are grounded in evolutionary psychology and emphasize the innate human demand for religion. Primordialists predict that religion does not decline in the modern era but will endure in perpetuity. Constructionist theories argue that religious demand is a human construct. Modernity initially energizes religion, but subsequently undermines it. Unpacking these ideal types is necessary in order to describe actual theorists of religion. Three distinctions within primordialism and constructionism are relevant. Namely those distinguishing: a) materialist from symbolist forms of constructionism; b) theories of origins from those pertaining to the reproduction of religion; and c) within reproduction, between theories of religious persistence and secularization. This typology helps to make sense of theories of religion by classifying them on the basis of their causal mechanisms, chronology and effects. In so doing, it opens up new sightlines for theory and research

Resistance of Bovine Spongiform Encephalopathy (BSE) Prions to Inactivation

Distinct prion strains often exhibit different incubation periods and patterns of neuropathological lesions. Strain characteristics are generally retained upon intraspecies transmission, but may change on transmission to another species. We investigated the inactivation of two related prions strains: BSE prions from cattle and mouse-passaged BSE prions, termed 301V. Inactivation was manipulated by exposure to sodium dodecyl sulfate (SDS), variations in pH, and different temperatures. Infectivity was measured using transgenic mouse lines that are highly susceptible to either BSE or 301V prions. Bioassays demonstrated that BSE prions are up to 1,000-fold more resistant to inactivation than 301V prions while Western immunoblotting showed that short acidic SDS treatments reduced protease-resistant PrPSc from BSE prions and 301V prions at similar rates. Our findings argue that despite being derived from BSE prions, mouse 301V prions are not necessarily a reliable model for cattle BSE prions. Extending these comparisons to human sporadic Creutzfeldt-Jakob disease and hamster Sc237 prions, we found that BSE prions were 10- and 106-fold more resistant to inactivation, respectively. Our studies contend that any prion inactivation procedures must be validated by bioassay against the prion strain for which they are intended to be used