101 research outputs found

    A Day in the Life of a Supercomputer

    Get PDF
    We are developing an interactive dashboard for visualizing the statistics of how users interact with nodes of a supercomputer. The intended purpose of the dashboard is to periodically provide with the overview of the load and bandwidth utilization of the nodes of a large supercomputer and details of each node and job as selected by the user. The dashboard will be interactive which will enable users to zoom in on interesting parts of the visualizations to investigate in details

    Catalysing organisational change within complex networks in the English National Health Service (NHS): an ethnographic account of disciplinary power

    Get PDF
    The English National Health Service (NHS) is a complex system, subject to constant change and organisational turmoil. In order for the NHS to deliver care that meets the needs of patients, it needs to be able to effectively manage organisational change. However, the existing literature emphasises planned approaches to change, which are not always suitable for such a complex environment and often fail to take into account underlying power dynamics. Adopting an explicitly Foucauldian research paradigm, the purpose of this research was therefore to explore how individual change leaders engage with power to facilitate the delivery of organisational change within network environments. Utilising an insider ethnographic research design, data was gathered from the Researcher’s substantive workplace within the English NHS. Taking place over 14 months between 2019 and 2020, the Researcher gathered over 200 hours’ worth of data and produced over 3000 pages of transcripts, utilising a combination of participant observation, interviews and document analysis. To support this triangulated approach to data collection, the Researcher established a forum to enable participants to have input into the emerging research in real-time, which provided multiple opportunities for debate and discussion. The Researcher also capitalised upon their status as a member of the community, to engage in deep and sustained reflexive practice, which added to the richness of the data. When viewed through a Foucauldian lens, the findings suggested that change leaders were able to engage with disciplinary power via the use of technologies, specific power/knowledge constructs that could be deployed to achieve specific effects. These power effects shaped how individuals worked upon their identities to become productive within a change management context. This complex dynamic, which also included the Researcher shaping themselves as a productive subject, had varying manifestations at the individual, team and network level which shaped how organisational change took place within the network environment. Conceptualising change management as a process of mobilising productive subjectivities therefore has significant implications for how change is approached within healthcare and other public administration settings

    Molecular evolution of the Bovini tribe (Bovidae, Bovinae): Is there evidence of rapid evolution or reduced selective constraint in Domestic cattle?

    Get PDF
    BACKGROUND: If mutation within the coding region of the genome is largely not adaptive, the ratio of nonsynonymous (dN) to synonymous substitutions (dS) per site (dN/dS) should be approximately equal among closely related species. Furthermore, dN/dS in divergence between species should be equivalent to dN/dS in polymorphisms. This hypothesis is of particular interest in closely related members of the Bovini tribe, because domestication has promoted rapid phenotypic divergence through strong artificial selection of some species while others remain undomesticated. We examined a number of genes that may be involved in milk production in Domestic cattle and a number of their wild relatives for evidence that domestication had affected molecular evolution. Elevated rates of dN/dS were further queried to determine if they were the result of positive selection, low effective population size (N(e)) or reduced selective constraint. RESULTS: We have found that the domestication process has contributed to higher dN/dS ratios in cattle, especially in the lineages leading to the Domestic cow (Bos taurus) and Mithan (Bos frontalis) and within some breeds of Domestic cow. However, the high rates of dN/dS polymorphism within B. taurus when compared to species divergence suggest that positive selection has not elevated evolutionary rates in these genes. Likewise, the low rate of dN/dS in Bison, which has undergone a recent population bottleneck, indicates a reduction in population size alone is not responsible for these observations. CONCLUSION: The effect of selection depends on effective population size and the selection coefficient (N(e)s). Typically under domestication both selection pressure for traits important in fitness in the wild and Ne are reduced. Therefore, reduced selective constraint could be responsible for the observed elevated evolutionary ratios in domesticated species, especially in B. taurus and B. frontalis, which have the highest dN/dS in the Bovini. This may have important implications for tests of selection such as the McDonald-Kreitman test. Surprisingly we have also detected a significant difference in the supposed neutral substitution rate between synonymous and noncoding sites in the Bovine genome, with a 30% higher rate of substitution at synonymous sites. This is due, at least in part, to an excess of the highly mutable CpG dinucleotides at synonymous sites, which will have implications for time of divergence estimates from molecular data

    Testing the neutral theory of molecular evolution using genomic data: a comparison of the human and bovine transcriptome

    Get PDF
    Despite growing evidence of rapid evolution in protein coding genes, the contribution of positive selection to intra- and interspecific differences in protein coding regions of the genome is unclear. We attempted to see if genes coding for secreted proteins and genes with narrow expression, specifically those preferentially expressed in the mammary gland, have diverged at a faster rate between domestic cattle (Bos taurus) and humans (Homo sapiens) than other genes and whether positive selection is responsible. Using a large data set, we identified groups of genes based on secretion and expression patterns and compared them for the rate of nonsynonymous (dN) and synonymous (dS) substitutions per site and the number of radical (Dr) and conservative (Dc) amino acid substitutions. We found evidence of rapid evolution in genes with narrow expression, especially for those expressed in the liver and mammary gland and for genes coding for secreted proteins. We compared common human polymorphism data with human-cattle divergence and found that genes with high evolutionary rates in human-cattle divergence also had a large number of common human polymorphisms. This argues against positive selection causing rapid divergence in these groups of genes. In most cases dN/dS ratios were lower in human-cattle divergence than in common human polymorphism presumably due to differences in the effectiveness of purifying selection between long-term divergence and short-term polymorphism

    A centrality measure for quantifying spread on weighted, directed networks

    Full text link
    While many centrality measures for complex networks have been proposed, relatively few have been developed specifically for weighted, directed (WD) networks. Here we propose a centrality measure for spread (of information, pathogens, etc.) through WD networks based on the independent cascade model (ICM). While deriving exact results for the ICM requires Monte Carlo simulations, we show that our centrality measure (Viral Centrality) provides excellent approximation to ICM results for networks in which the weighted strength of cycles is not too large. We show this can be quantified with the leading eigenvalue of the weighted adjacency matrix, and we show that Viral Centrality outperforms other common centrality measures in both simulated and empirical WD networks.Comment: 3 figure

    Wearable Positive End-Expiratory Pressure Valve Improves Exercise Performance

    Get PDF
    Positive end-expiratory pressure (PEEP) provides benefits to pulmonary patients, yet effects in healthy, exercising adults are unknown. PURPOSE: We designed two experiments (EXP) to test a novel PEEP (4.2 cmH2O PEEP) mouthpiece (PMP) on maximal cycling performance of physically active volunteers. METHODS: EXP-1 PMP vs. control (CON) mouthpiece (N=9, Age=30±2 yr, Weight=72.2±3.7 kg, BMI=24.4±1.2, 5♂); and EXP-2 PMP vs. no mouthpiece (NMP) (N=10, Age=27±1 yr, Weight=76.7±3.6 kg, BMI=23.9±0.8, ♂). Exercise test procedures for both experiments were identical. On Day 1, under the first mouthpiece condition assigned at random subjects performed graded exercise cycling testing (GXT) (Corival®) for VO2peak (ml*kg*min-1), oxygen pulse (mlO2*bt) (O2pulse), GXT endurance time (s) (GXT-T), and VO2(ml*kg*min-1)-at-ventilatory-threshold (VO2 @VT). Subjects returned 72 h later (Day 2), to complete an endurance ride timed (s)to exhaustion (VTER) at an intensity equivalent to their VO2 @VT power (W). One week later, subjects repeated exercise testing protocols (Days 3 & 4, time-of-day controlled) under the alternate mouthpiece condition. RESULTS: Selected outcomes were as follows (paired T-test, *PMP vs. CON, respectively: VO2peak=45.2±2.4* vs. 42.4±2.3; VO2@VT=33.7±2.0 vs. 32.3±1.6; GXT-T=521.7±73.4* vs. 495.3±72.8; VTER=846.2±166.0 vs. 743.1±124.7; O2pulse=24.5±1.4* vs. 23.1±1.3. PMP vs. NMP, respectively: VO2peak=43.3±1.6* vs. 41.7±1.6; VO2@AT=31.1±1.2* vs. 29.1±1.3; GXT-T=511.7*±49.6 vs. 486.4±49.6; VTER 872.4±134.0 vs. 792.9 ± 122.4; O2pulse=24.1±0.9* vs. 23.4±0.9. CONCLUSION: These results demonstrate that the novel PEEP mouthpiece we tested confers a significant performance benefit to cyclists completing high intensity exercise. By extension, it is likely to be an advantage in any physical activity having an aerobic component

    Medial open transversus abdominis plane (MOTAP) catheters for analgesia following open liver resection: study protocol for a randomized controlled trial

    Get PDF
    Background: The current standard for pain control following liver surgery is intravenous, patient-controlled analgesia (IV PCA) or epidural analgesia. We have developed a modification of a regional technique called medial open transversus abdominis plane (MOTAP) catheter analgesia. The MOTAP technique involves surgically placed catheters through the open surgical site into a plane between the internal oblique muscle and the transverse abdominis muscle superiorly. The objective of this trial is to assess the efficacy of this technique. Methods/design: This protocol describes a multicentre, prospective, blinded, randomized controlled trial. One hundred and twenty patients scheduled for open liver resection through a subcostal incision will be enrolled. All patients will have two MOTAP catheters placed at the conclusion of surgery. Patients will be randomized to one of two parallel groups: experimental (local anaesthetic through MOTAP catheters) or placebo (normal saline through MOTAP catheters). Both groups will also receive IV PCA. The primary endpoint is mean cumulative postoperative opioid consumption over the first 2 postoperative days (48 hours). Secondary outcomes include pain intensity, patient functional outcomes, and the incidence of complications. Discussion: This trial has been approved by the ethics boards at participating centres and is currently enrolling patients. Data collection will be completed by the end of 2014 with analysis mid-2015 and publication by the end of 2015. Trial registration: The study is registered with http://clinicaltrials.gov (NCT01960049; 23 September 2013)This research is supported by the Innovation Fund of the Alternative Funding Plan from the Academic Health Sciences Centres of Ontario

    A Genome Wide Survey of SNP Variation Reveals the Genetic Structure of Sheep Breeds

    Get PDF
    The genetic structure of sheep reflects their domestication and subsequent formation into discrete breeds. Understanding genetic structure is essential for achieving genetic improvement through genome-wide association studies, genomic selection and the dissection of quantitative traits. After identifying the first genome-wide set of SNP for sheep, we report on levels of genetic variability both within and between a diverse sample of ovine populations. Then, using cluster analysis and the partitioning of genetic variation, we demonstrate sheep are characterised by weak phylogeographic structure, overlapping genetic similarity and generally low differentiation which is consistent with their short evolutionary history. The degree of population substructure was, however, sufficient to cluster individuals based on geographic origin and known breed history. Specifically, African and Asian populations clustered separately from breeds of European origin sampled from Australia, New Zealand, Europe and North America. Furthermore, we demonstrate the presence of stratification within some, but not all, ovine breeds. The results emphasize that careful documentation of genetic structure will be an essential prerequisite when mapping the genetic basis of complex traits. Furthermore, the identification of a subset of SNP able to assign individuals into broad groupings demonstrates even a small panel of markers may be suitable for applications such as traceability

    Sheep Genome Functional Annotation Reveals Proximal Regulatory Elements Contributed to The Evolution of Modern Breeds

    Get PDF
    Domestication fundamentally reshaped animal morphology, physiology and behaviour, offering the opportunity to investigate the molecular processes driving evolutionary change. Here we assess sheep domestication and artificial selection by comparing genome sequence from 43 modern breeds (Ovis aries) and their Asian mouflon ancestor (O. orientalis) to identify selection sweeps. Next, we provide a comparative functional annotation of the sheep genome, validated using experimental ChIP-Seq of sheep tissue. Using these annotations, we evaluate the impact of selection and domestication on regulatory sequences and find that sweeps are significantly enriched for protein coding genes, proximal regulatory elements of genes and genome features associated with active transcription. Finally, we find individual sites displaying strong allele frequency divergence are enriched for the same regulatory features. Our data demonstrate that remodelling of gene expression is likely to have been one of the evolutionary forces that drove phenotypic diversification of this common livestock species
    corecore