173 research outputs found

    An empirical investigation of recent acquisition activity in the UK

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    This thesis was submitted for the degree of Doctor of Philosophy and awarded by Brunel University.This thesis is concerned with acquisition activity in the UK and, specifically the prediction of takeovers. This is an important area for research for three reasons. Firstly, acquisition activity involves a small number of companies but creates very large sums of money. Secondly, acquisition activity can alter the composition of a company or an entire industry very rapidly making it a valuable tool for business. Lastly, there are many different topics within this field, allowing for a wealth of empirical analysis. A considerable amount of early research was limited to observation leaving some theories with little empirical backing. In addition, many earlier papers do not consider economic conditions. Recently the UK has experienced a boom and a recession. Both of these events may have effected acquisition activity and will be incorporated into this study. This thesis tackles several issues concerning acquisitions. Firstly, it deals with the level of acquisition activity and determines whether this behaviour is random or predictable. If it is predictable it should be possible to model this behaviour using appropriate indicators. The second issue is the prediction of takeovers identifying the companies likely to become involved in acquisitions. This study incorporates both accounting data and macro-economic factors. Finally, there is an analysis of acquisition benefits, considering the impact on share prices. The findings here suggest that the level of acquisition activity is predictable. However, in a boom it rises to an unprecedented level, demonstrating bubble-like properties. The empirical work concerning the prediction of acquisitions suggests that takeovers increase firm efficiency and remove poor managers. Furthermore, acquiring companies seek expansion and increased investment opportunities. Examining macro-economic conditions suggests funding and cash flow are important when acquiring in a boom, whilst productivity and market protection are vital in a recession. Finally, it appears that the target firm shareholders benefit irrespective of the outcome of the takeover

    Developing an online learning community through an open reflective assessment

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    The concepts of learning communities, open educational practices and co-created teaching and learning are topics of current debate, particularly since the switch to online learning in 2020/21 because of the COVID-19 pandemic. This case study uses student feedback to evaluate a new assessment method introduced within an online distance learning Master of Public Health programme. The assessment required students to blog about their motivations for studying public health, submitting their reflections to an open online platform, resulting in the co-creation of a shared, open-learning resource for current and future students. The assessment design was informed by the benefits of open educational practices and co-created teaching and learning, with the overall aim of developing an online learning community that will continue to grow and develop beyond the initial assessment and cohort. Feedback suggests that the open, reflective nature of the assessment had a positive impact on the student learning experience and contributed towards a sense of learning community through enhanced social cohesion within the group

    RNA-seq Brings New Insights to the Intra-Macrophage Transcriptome of Salmonella Typhimurium.

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    Salmonella enterica serovar Typhimurium is arguably the world's best-understood bacterial pathogen. However, crucial details about the genetic programs used by the bacterium to survive and replicate in macrophages have remained obscure because of the challenge of studying gene expression of intracellular pathogens during infection. Here, we report the use of deep sequencing (RNA-seq) to reveal the transcriptional architecture and gene activity of Salmonella during infection of murine macrophages, providing new insights into the strategies used by the pathogen to survive in a bactericidal immune cell. We characterized 3583 transcriptional start sites that are active within macrophages, and highlight 11 of these as candidates for the delivery of heterologous antigens from Salmonella vaccine strains. A majority (88%) of the 280 S. Typhimurium sRNAs were expressed inside macrophages, and SPI13 and SPI2 were the most highly expressed pathogenicity islands. We identified 31 S. Typhimurium genes that were strongly up-regulated inside macrophages but expressed at very low levels during in vitro growth. The SalComMac online resource allows the visualisation of every transcript expressed during bacterial replication within mammalian cells. This primary transcriptome of intra-macrophage S.-Typhimurium describes the transcriptional start sites and the transcripts responsible for virulence traits, and catalogues the sRNAs that may play a role in the regulation of gene expression during infection

    Evasion of MAIT cell recognition by the African Salmonella Typhimurium ST313 pathovar that causes invasive disease

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    Mucosal-associated invariant T (MAIT) cells are innate T lymphocytes activated by bacteria that produce vitamin B2 metabolites. Mouse models of infection have demonstrated a role for MAIT cells in antimicrobial defense. However, proposed protective roles of MAIT cells in human infections remain unproven and clinical conditions associated with selective absence of MAIT cells have not been identified. We report that typhoidal and nontyphoidal Salmonella enterica strains activate MAIT cells. However, S. Typhimurium sequence type 313 (ST313) lineage 2 strains, which are responsible for the burden of multidrug-resistant nontyphoidal invasive disease in Africa, escape MAIT cell recognition through overexpression of ribB. This bacterial gene encodes the 4-dihydroxy-2-butanone-4-phosphate synthase enzyme of the riboflavin biosynthetic pathway. The MAIT cell-specific phenotype did not extend to other innate lymphocytes. We propose that ribB overexpression is an evolved trait that facilitates evasion from immune recognition by MAIT cells and contributes to the invasive pathogenesis of S. Typhimurium ST313 lineage 2

    Sequencing PDX1 (insulin promoter factor 1) in 1788 UK individuals found 5% had a low frequency coding variant, but these variants are not associated with Type 2 diabetes

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    OnlineOpen Article. This is a copy of an article published in Diabetic Medicine. This journal is available online at: http://onlinelibrary.wiley.com/journal/10.1111/(ISSN)1464-5491Genome-wide association studies have identified >30 common variants associated with Type 2 diabetes (>5% minor allele frequency). These variants have small effects on individual risk and do not account for a large proportion of the heritable component of the disease. Monogenic forms of diabetes are caused by mutations that occur in <1:2000 individuals and follow strict patterns of inheritance. In contrast, the role of low frequency genetic variants (minor allele frequency 0.1-5%) in Type 2 diabetes is not known. The aim of this study was to assess the role of low frequency PDX1 (also called IPF1) variants in Type 2 diabetes

    Public health surveillance in the UK revolutionises our understanding of the invasive Salmonella Typhimurium epidemic in Africa

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    Background:The ST313 sequence type ofSalmonellaTyphimurium causes invasive non-typhoidal salmonellosis and wasthought to be confined to sub-Saharan Africa. Two distinct phylogenetic lineages of African ST313 have been identified.Methods:We analysed the whole genome sequences ofS. Typhimurium isolates from UK patients that weregenerated following the introduction of routine whole-genome sequencing (WGS) ofSalmonella entericabyPublic Health England in 2014.Results:We found that 2.7% (84/3147) ofS. Typhimurium from patients in England and Wales were ST313 and wereassociated with gastrointestinal infection. Phylogenetic analysis revealed novel diversity of ST313 that distinguishedUK-linked gastrointestinal isolates from African-associated extra-intestinal isolates. The majority of genome degradationof African ST313 lineage 2 was conserved in the UK-ST313, but the African lineages carried a characteristic prophageand antibiotic resistance gene repertoire. These findings suggest that a strong selection pressure exists for certainhorizontally acquired genetic elements in the African setting. One UK-isolated lineage 2 strain that probably originatedin Kenya carried a chromosomally locatedblaCTX-M-15, demonstrating the continual evolution of this sequence type inAfrica in response to widespread antibiotic usage.Conclusions:The discovery of ST313 isolates responsible for gastroenteritis in the UK reveals new diversity in thisimportant sequence type. This study highlights thepower of routine WGS by public health agencies to makeepidemiologically significant deductions that would be missed by conventional microbiological methods. Wespeculate that the niche specialisation of sub-Saharan African ST313 lineages is driven in part by the acquisitionof accessory genome elements
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