A comparison of EEG spectral entropy with conventional quantitative EEG at varying depths of sevoflurane anaesthesia

Background and Aim: Recently an electroencephalographic (EEG) spectral entropy module (M-ENTROPY) for an anaesthetic monitor has become commercially available. We compared its performance as an indicator of the state of anaesthesia with that of an older conventional quantitative EEG (QEEG) module (M-EEG) by the same manufacturer (Datex-Ohmeda Division, Instrumentarium Corp., Helsinki, Finland). Methods: There were 40 ASA class I or II subjects, aged between 16-60 years, who underwent elective abdominal surgery. EEG data were collected from the printouts of the respective modules. The data presented here were related to four levels of anaesthesia: Pre-anaesthetic wakefulness (state A), 2% sevoflurane endtidal (ET) concentration after completion of surgery (state B), low ET sevoflurane concentrations (~ 0.5%) just prior to regaining responsiveness (state C), and post-anaesthetic responsiveness (state D). Results: In terms of the prediction probability (Pk statistic), response entropy (RE) and state entropy (SE) produced higher values (0.95-1.0) than the best performing QEEG variable, frontal amplitude (0.86-0.95). Only RE scores did not overlap between states A and B or between B and D. The misclassification of subjects between states C and D was far lower for RE (28%) than for any of the conventional QEEG measures (>90%). Conclusion: In on-line monitoring spectral entropy is superior in distinguishing states of anaesthesia and is also easier to use than conventional QEEG. It is speculated that the artefact rejection strategies accorded spectral entropy might significantly benefit conventional QEEG analysis.Key words: EEG spectral entropy, conventional QEEG, sevoflurane anaesthesiaSouthern African Journal of Anaesthesia & Analgesia Vol. 11 (3) 2005: 89-9

Secondary sex ratio in assisted reproduction: an analysis of 1 376 454 treatment cycles performed in the UK.

STUDY QUESTION: Does ART impact the secondary sex ratio (SSR) when compared to natural conception? SUMMARY ANSWER: IVF and ICSI as well as the stage of embryo transfer does impact the overall SSR. WHAT IS KNOWN ALREADY: The World Health Organization quotes SSR for natural conception to range between 103 and 110 males per 100 female births. STUDY DESIGN SIZE DURATION: A total of 1 376 454 ART cycles were identified, of which 1 002 698 (72.8%) cycles involved IVF or ICSI. Of these, 863 859 (85.2%) were fresh cycles and 124 654 (12.4%) were frozen cycles. Missing data were identified in 14 185 (1.4%) cycles. PARTICIPANTS/MATERIALS SETTING METHODS: All cycles recorded in the anonymized UK Human Fertilisation and Embryology Authority (HFEA) registry database between 1991 and 2016 were analysed. All singleton live births were included, and multiple births were excluded to avoid duplication. MAIN RESULTS AND THE ROLE OF CHANCE: The overall live birth rate per cycle for all IVF and ICSI treatments was 26.2% (n = 262 961), and the singleton live birth rate per cycle was 17.1% (n = 171 399). The overall SSR for this study was 104.0 males per 100 female births (binomial exact 95% CI: 103.1-105.0) for all IVF and ICSI cycles performed in the UK recorded through the HFEA. This was comparable to the overall SSR for England and Wales at 105.3 males per 100 female births (95% CI: 105.2-105.4) from 1991 to 2016 obtained from the Office of National Statistics database. Male predominance was seen with conventional insemination in fresh IVF treatment cycles (SSR 110.0 males per 100 female births; 95% CI: 108.6-111.5) when compared to micro-injection in fresh ICSI treatment cycles (SSR 97.8 males per 100 female births; 95% CI: 96.5-99.2; odds ratio (OR) 1.16, 95% CI 1.12-1.19, P < 0.0001), as well as with blastocyst stage embryo transfers (SSR 104.8 males per 100 female births; 95% CI: 103.5-106.2) when compared to a cleavage stage embryo transfer (SSR 101.2 males per 100 female births; 95% CI: 99.3-103.1; OR 1.03, 95% CI 1.01-1.06, P = 0.011) for all fertilization methods. LIMITATIONS REASONS FOR CAUTION: The quality of the data relies on the reporting system. Furthermore, success rates through ART have improved since 1991, with an increased number of blastocyst stage embryo transfers. WIDER IMPLICATIONS OF THE FINDINGS: This is the largest study to date evaluating the impact of ART on SSR. The results demonstrate that, overall, ART does have an impact on the SSR when assessed according to the method of fertilization (ICSI increased female births while IVF increased males). However, given the ratio of IVF to ICSI cycles at present with 60% of cycles from IVF and 40% from ICSI, the overall SSR for ART closely reflects the population SSR for, largely, natural conceptions in England and Wales. STUDY FUNDING/COMPETING INTERESTS: The study received no funding. C.M.B. is a member of the independent data monitoring group for a clinical endometriosis trial by ObsEva. He is on the scientific advisory board for Myovant and medical advisory board for Flo Health. He has received research grants from Bayer AG, MDNA Life Sciences, Volition Rx and Roche Diagnostics as well as from Wellbeing of Women, Medical Research Council UK, the NIH, the UK National Institute for Health Research and the European Union. He is the current Chair of the Endometriosis Guideline Development Group for ESHRE and was a co-opted member of the Endometriosis Guideline Group by the UK National Institute for Health and Care Excellence (NICE). I.G. has received research grants from Wellbeing of Women, the European Union and Finox. TRIAL REGISTRATION NUMBER: Not applicable

Controls on gut phosphatisation : the trilobites from the Weeks Formation Lagerstätte (Cambrian; Utah)

Despite being internal organs, digestive structures are frequently preserved in Cambrian Lagerstätten. However, the reasons for their fossilisation and their biological implications remain to be thoroughly explored. This is particularly true with arthropods--typically the most diverse fossilised organisms in Cambrian ecosystems--where digestive structures represent an as-yet underexploited alternative to appendage morphology for inferences on their biology. Here we describe the phosphatised digestive structures of three trilobite species from the Cambrian Weeks Formation Lagerstätte (Utah). Their exquisite, three-dimensional preservation reveals unique details on trilobite internal anatomy, such as the position of the mouth and the absence of a differentiated crop. In addition, the presence of paired pygidial organs of an unknown function is reported for the first time. This exceptional material enables exploration of the relationships between gut phosphatisation and the biology of organisms. Indeed, soft-tissue preservation is unusual in these fossils as it is restricted to the digestive structures, which indicates that the gut played a central role in its own phosphatisation. We hypothesize that the gut provided a microenvironment where special conditions could develop and harboured a source of phosphorus. The fact that gut phosphatization has almost exclusively been observed in arthropods could be explained by their uncommon ability to store ions (including phosphorous) in their digestive tissues. However, in some specimens from the Weeks Formation, the phosphatisation extends to the entire digestive system, suggesting that trilobites might have had some biological particularities not observed in modern arthropods. We speculate that one of them might have been an increased capacity for ion storage in the gut tissues, related to the moulting of their heavily-mineralised carapace

Activation of the innate immune receptor Dectin-1 upon formation of a 'phagocytic synapse'.

Innate immune cells must be able to distinguish between direct binding to microbes and detection of components shed from the surface of microbes located at a distance. Dectin-1 (also known as CLEC7A) is a pattern-recognition receptor expressed by myeloid phagocytes (macrophages, dendritic cells and neutrophils) that detects β-glucans in fungal cell walls and triggers direct cellular antimicrobial activity, including phagocytosis and production of reactive oxygen species (ROS). In contrast to inflammatory responses stimulated upon detection of soluble ligands by other pattern-recognition receptors, such as Toll-like receptors (TLRs), these responses are only useful when a cell comes into direct contact with a microbe and must not be spuriously activated by soluble stimuli. In this study we show that, despite its ability to bind both soluble and particulate β-glucan polymers, Dectin-1 signalling is only activated by particulate β-glucans, which cluster the receptor in synapse-like structures from which regulatory tyrosine phosphatases CD45 and CD148 (also known as PTPRC and PTPRJ, respectively) are excluded (Supplementary Fig. 1). The 'phagocytic synapse' now provides a model mechanism by which innate immune receptors can distinguish direct microbial contact from detection of microbes at a distance, thereby initiating direct cellular antimicrobial responses only when they are required

Evaluation of single and double-locus real-time PCR assays for methicillin-resistant Staphylococcus aureus (MRSA) surveillance

<p>Abstract</p> <p>Background</p> <p>Methicillin-resistant <it>Staphylococcus aureus </it>(MRSA) is a human pathogen, representing an infection control challenge. Conventional MRSA screening takes up to three days, therefore development of rapid detection is essential. Real time-PCR (rt-PCR) is the fastest method fulfilling this task. All currently published or commercially available rt-PCR MRSA assays relay on single or double-locus detection. Double-locus assays are based on simultaneous detection of <it>mecA </it>gene and a <it>S. aureus</it>-specific gene. Such assays cannot be applied on clinical samples, which often contain both coagulase-negative staphylococci (CoNS) and <it>S. aureus</it>, either of which can carry <it>mecA</it>. Single-locus assays are based on detection of the staphylococcal cassette chromosome <it>mec </it>(SCC<it>mec</it>) element and the <it>S. aureus</it>-specific <it>orfX </it>gene, assuming that it is equivalent to <it>mecA </it>detection.</p> <p>Findings</p> <p>Parallel evaluation of several published single and double-locus rt-PCR MRSA assays of 150 pure culture strains, followed by analysis of 460 swab-derived clinical samples which included standard identification, susceptibility testing, followed by PCR detection of staphylococcal suspected isolates and in-PCR mixed bacterial populations analysis indicated the following findings.</p> <p>Pure cultures analysis indicated that one of the single-locus assay had very high prevalence of false positives (Positive predictive value = 77.8%) and was excluded from further analysis. Analysis of 460 swab-derived samples indicated that the second single-locus assay misidentified 16 out of 219 MRSA's and 13 out of 90 methicillin-sensitive <it>S</it>. <it>aureus</it>'s (MSSA) were misidentified as MRSA's. The double-locus detection assay misidentified 55 out of 90 MSSA's. 46 MSSA containing samples were misidentified as MRSA and 9 as other than <it>S. aureus </it>ending with low positive predicted value (<85%) and very low specificity (<62%).</p> <p>Conclusion</p> <p>The results indicate that high prevalence of false-positive and false-negative reactions occurs in such assays.</p

MultiMetEval: comparative and multi-objective analysis of genome-scale metabolic models

Comparative metabolic modelling is emerging as a novel field, supported by the development of reliable and standardized approaches for constructing genome-scale metabolic models in high throughput. New software solutions are needed to allow efficient comparative analysis of multiple models in the context of multiple cellular objectives. Here, we present the user-friendly software framework Multi-Metabolic Evaluator (MultiMetEval), built upon SurreyFBA, which allows the user to compose collections of metabolic models that together can be subjected to flux balance analysis. Additionally, MultiMetEval implements functionalities for multi-objective analysis by calculating the Pareto front between two cellular objectives. Using a previously generated dataset of 38 actinobacterial genome-scale metabolic models, we show how these approaches can lead to exciting novel insights. Firstly, after incorporating several pathways for the biosynthesis of natural products into each of these models, comparative flux balance analysis predicted that species like Streptomyces that harbour the highest diversity of secondary metabolite biosynthetic gene clusters in their genomes do not necessarily have the metabolic network topology most suitable for compound overproduction. Secondly, multi-objective analysis of biomass production and natural product biosynthesis in these actinobacteria shows that the well-studied occurrence of discrete metabolic switches during the change of cellular objectives is inherent to their metabolic network architecture. Comparative and multi-objective modelling can lead to insights that could not be obtained by normal flux balance analyses. MultiMetEval provides a powerful platform that makes these analyses straightforward for biologists. Sources and binaries of MultiMetEval are freely available from https://github.com/PiotrZakrzewski/MetEv​al/downloads

Error Rates, Decisive Outcomes and Publication Bias with Several Inferential Methods

Correction to this article published Hopkins, W.G. & Batterham, A.M. Sports Med (2016) 46: 923. doi:10.1007/s40279-016-0530-

Magnetic resonance imaging in patients with meningitis induced hearing loss

The aim of this multicentre study was to compare T1 with T2 weighted MRI scans of the labyrinth after meningitis and to investigate whether waiting with scanning improved the reliability of diagnosing an ongoing process such as cochlear osteogenesis. Forty-five patients were included who suffered from meningitis induced hearing loss (radiological imaging <1 year after meningitis). Twenty-one gadolinium enhanced T1 and 45 T2 weighted MRI scans were scored by two radiologists regarding the condition of the labyrinth. These radiological observations were compared with the condition of the cochlea as described during cochlear implantation. A higher percentage of agreement with surgery was found for T2 (both radiologists 73%) than for T1 weighted MRI scans (radiologist 1: 62%, radiologist 2: 67%), but this difference is not significant. There was no significant difference between early (0–3 months) and late (>3 months) scanning, showing that radiological imaging soon after meningitis allows early diagnosis without suffering from a lower agreement with surgical findings

Genome-wide signatures of convergent evolution in echolocating mammals

Evolution is typically thought to proceed through divergence of genes, proteins, and ultimately phenotypes(1-3). However, similar traits might also evolve convergently in unrelated taxa due to similar selection pressures(4,5). Adaptive phenotypic convergence is widespread in nature, and recent results from a handful of genes have suggested that this phenomenon is powerful enough to also drive recurrent evolution at the sequence level(6-9). Where homoplasious substitutions do occur these have long been considered the result of neutral processes. However, recent studies have demonstrated that adaptive convergent sequence evolution can be detected in vertebrates using statistical methods that model parallel evolution(9,10) although the extent to which sequence convergence between genera occurs across genomes is unknown. Here we analyse genomic sequence data in mammals that have independently evolved echolocation and show for the first time that convergence is not a rare process restricted to a handful of loci but is instead widespread, continuously distributed and commonly driven by natural selection acting on a small number of sites per locus. Systematic analyses of convergent sequence evolution in 805,053 amino acids within 2,326 orthologous coding gene sequences compared across 22 mammals (including four new bat genomes) revealed signatures consistent with convergence in nearly 200 loci. Strong and significant support for convergence among bats and the dolphin was seen in numerous genes linked to hearing or deafness, consistent with an involvement in echolocation. Surprisingly we also found convergence in many genes linked to vision: the convergent signal of many sensory genes was robustly correlated with the strength of natural selection. This first attempt to detect genome-wide convergent sequence evolution across divergent taxa reveals the phenomenon to be much more pervasive than previously recognised

Potentiating antibacterial activity by predictably enhancing endogenous microbial ROS production

The ever-increasing incidence of antibiotic-resistant infections combined with a weak pipeline of new antibiotics has created a global public health crisis1. Accordingly, novel strategies for enhancing our antibiotic arsenal are needed. As antibiotics kill bacteria in part by inducing reactive oxygen species (ROS)2–4, we reasoned that targeting microbial ROS production might potentiate antibiotic activity. Here we show that ROS production can be predictably enhanced in Escherichia coli, increasing the bacteria’s susceptibility to oxidative attack. We developed an ensemble, genome-scale metabolic modeling approach capable of predicting ROS production in E. coli. The metabolic network was systematically perturbed and its flux distribution analyzed to identify targets predicted to increase ROS production. In silico–predicted targets were experimentally validated and shown to confer increased susceptibility to oxidants. Validated targets also increased susceptibility to killing by antibiotics. This work establishes a systems-based method to tune ROS production in bacteria and demonstrates that increased microbial ROS production can potentiate killing by oxidants and antibiotics