In Search of the Postmodern Utopia: Ben Okri’s In Arcadia

This essay explores how Ben Okri’s most recent novel, In Arcadia(2002), attempts to reconstruct the possibility of utopia in the face of a fragmentation of identity and destruction of determinate certainties affecting contemporary society in the aftermath of postmodernism. By tracing the intertextual relations existing between this work and earlier works in an intellectual/literary tradition that extends from Theocritus and Virgil through Dante, More, Milton, Sannazzaro, Sidney and others, Fox shows how Okri develops the proposition that men and women confronting an ‘empty universe where the mind spins in uncertainty and repressed terror’ can recover sanity through art. Even though, in Okri’s vision, the world may be ‘a labyrinth without an exit’, presided over by Death without any hint of transcendence, men and women, he concludes, can recover paradise through the ‘painting of the mind’ which can creative complete forms that can be fed into ‘spirit’s factory for the production of reality’. This generative activity, which is at the heart of the Arcadian vision, in Okri’s view, has the power to make life a place of ‘secular miracles’, despite the limitations imposed upon it by the realities of finitude and death. The essay concludes by suggesting that Okri’s concept of utopia is very close to Kant’s idea of Aufklärung as expounded by Michel Foucault –– that is, neither a world era, nor an event whose signs are perceived, nor the dawning of an accomplishment, but rather a process of which men and women are at once elements and agents, and which occurs to the extent that they decide to be its voluntary actors. While in some respects Okri’s vision is strikingly similar to certain of its antecedents, it is thus nevertheless distinctively postmodern in the ways in which it is inflected

Introduction: Rethinking Utopia in the Wake of Postmodernism

This introduction to the special issue of Portal on 'Strange Localities: Utopias, Intellectuals, and Identities' identifies the problematical issues in postmodernism and postcolonial theory that are addressed by the essays in the special issue. It then gives an overview of the findings of the essays, and concludes by suggesting that the utopian impulse continues to be expressed in contemporary thought and writing with the aim of bringing utopian hope into an effective relationship with praxis in the here and now

A process synthesis approach to flowsheet design for the minimization of carbon dioxide emissions

There is increasing pressure on industries to increase their productivity while simultaneously reducing their environmental impact. In order to meet these new challenges, energy and raw materials need to be put to the best use they can be. Typically the features of a process are fixed at an early stage in a design. While doing so allows a design to be conveniently arranged into discrete stages, it also results in the loss of many opportunities for innovation. In order to preserve both the chance for innovation and ease of management, new and systematic methods are needed to design processes. The purpose of this research is to demonstrate the use of a novel method of synthesizing process flowsheets, using a graphical tool which we called the GH-space, with the overall goal of minimizing carbon emissions while making the best use of raw materials and for a given production. Typically mass, energy and work balances are done on flowsheets as a means of analysis. In other words, the flowsheet determines the balances. Unfortunately, once the flowsheet and chemistry of the process has been decided, most of the opportunities for improvement and innovation have been lost. The GH-space technique uses fundamental thermodynamic principles to allow the mass, energy and work balances to define targets for the performance of a process. Furthermore processes and unit operations can be defined as vectors in the GH-space. Using the targets, one can combine the vector processes in such a way as to approach the target. These vector processes, and the way they are combined, can then be interpreted in terms of flowsheets. This is opposite to what is normally done and allows the process balances to determine what the best flowsheet might look like, allowing for great innovation from the very start of a design. In addition to this, probably the greatest advantage of the GH-space technique is that processes of great complexity can all be analyzed on a set of two-dimensional axes. Every process that converts some feed material to a product material has a heat and a work associated with it in order to perform that conversion. Using the relationship that exists between heat and work allows the target of a process to be determined and for flowsheets to be formulated that allow these targets to be met. In this research the flows of heat and work are illustrated with the analogy of a heat engine. This is not the only way for heat and work to flow between process units but it allows for convenient illustration of the heat and work interaction between individual process units. Three case studies were chosen for their reputations as high carbon dioxide emitters: Coal Gasification, Methane Steam Reforming and Fischer-Tropsch synthesis. The GH-space method was then applied to these three examples to determine if these emissions were just a price that had to be paid or if there was any room for improvement. The case studies shown herein were ideal cases to show the power and flexibility of the technique as well as illustrate a method of using the technique, there is a great deal of additional details that would still need to be considered for a practical, functioning, plant to be built, such as catalysis and materials of construction, to name only two. While the GH-space provides insight into what the theoretical maximum efficiency might look like it does not necessarily show what the absolute maximum efficiency might be. Another advantage of the GH-space is that it can handle as little or as much detail as is desired. It was shown in this work that with clear understanding of the flows of mass, energy and work within a process it is possible to design process flowsheets that are potentially carbon negative, produce the intended product and also produce power as a co-product

Genomic analysis of global Staphylococcus argenteus strains reveals distinct lineages with differing virulence and antibiotic resistance gene content

This work was funded by the Scottish Executive via the Chief Scientists Office through the provision of a grant to establish the Scottish Healthcare Associated Infection Prevention Institute (SHAIPI).Infections due to Staphylococcus argenteus have been increasingly reported worldwide and the microbe cannot be distinguished from Staphylococcus aureus by standard methods. Its complement of virulence determinants and antibiotic resistance genes remain unclear, and how far these are distinct from those produced by S. aureus remains undetermined. In order to address these uncertainties, we have collected 132 publicly available sequences from fourteen different countries, including the United Kingdom, between 2005 and 2018 to study the global genetic structure of the population. We have compared the genomes for antibiotic resistance genes, virulence determinants and mobile genetic elements such as phages, pathogenicity islands and presence of plasmid groups between different clades. 20% (n = 26) isolates were methicillin resistant harboring a mecA gene and 88% were penicillin resistant, harboring the blaZ gene. ST2250 was identified as the most frequent strain, but ST1223, which was the second largest group, contained a marginally larger number of virulence genes compared to the other STs. Novel S. argenteus pathogenicity islands were identified in our isolates harboring tsst-1, seb, sec3, ear, selk, selq toxin genes, as well as chromosomal clusters of enterotoxin and superantigen-like genes. Strain-specific type I modification systems were widespread which would limit interstrain transfer of genetic material. In addition, ST2250 possessed a CRISPR/Cas system, lacking in most other STs. S. argenteus possesses important genetic differences from S. aureus, as well as between different STs, with the potential to produce distinct clinical manifestations.Publisher PDFPeer reviewe

Origin, maintenance and spread of antibiotic resistance genes within plasmids and chromosomes of bloodstream isolates of Escherichia coli

The work was funded by the Scottish Executive via the Chief Scientists Office through the provision of a grant to establish the Scottish Healthcare Associated Infection Prevention Institute (SHAIPI).Blood stream invasion by Escherichia coli is the commonest cause of bacteremia in the UK and elsewhere with an attributable mortality of about 15–20 %; antibiotic resistance to multiple agents is common in this microbe and is associated with worse outcomes. Genes conferring antimicrobial resistance, and their frequent location on horizontally transferred genetic elements is well-recognised, but the origin of these determinants, and their ability to be maintained and spread within clinically-relevant bacterial populations is unclear. Here, we set out to examine the distribution of antimicrobial resistance genes in chromosomes and plasmids of 16 bloodstream isolates of E. coli from patients within Scotland, and how these genes are maintained and spread. Using a combination of short and long-read whole genome sequencing methods, we were able to assemble complete sequences of 44 plasmids, with 16 Inc group F and 20 col plasmids; antibiotic resistance genes located almost exclusively within the F group. blaCTX-M15 genes had re-arranged in some strains into the chromosome alone (five strains), while others contained plasmid copies alone (two strains). Integrons containing multiple antibiotic genes were widespread in plasmids, notably many with a dfrA7 gene encoding resistance to trimethoprim, thus linking trimethoprim resistance to the other antibiotic resistance genes within the plasmids. This will allow even narrow spectrum antibiotics such as trimethoprim to act as a selective agent for plasmids containing antibiotic resistance genes mediating much broader resistance, including blaCTX-M15. To our knowledge, this is the first analysis to provide complete sequence data of chromosomes and plasmids in a collection of pathogenic human bloodstream isolates of E. coli. Our findings reveal the interplay between plasmids and integrative and conjugative elements in the maintenance and spread of antibiotic resistance genes within pathogenic E. coli.Publisher PDFPeer reviewe

Minocycline 200 mg or 400 mg versus placebo for mild Alzheimer's disease: the MADE Phase II, three-arm RCT

Background: Minocycline is an anti-inflammatory drug and protects against the toxic effects of β-amyloid in vitro and in animal models of Alzheimer’s disease. To the best of our knowledge, no randomised placebo-controlled clinical trials in patients with Alzheimer’s disease looking at the efficacy and tolerability of minocycline have been carried out. Objectives: The trial investigated whether or not minocycline was superior to placebo in slowing down the rate of decline in cognitive and functional ability over 2 years. The safety and tolerability of minocycline were also assessed. Design: A Phase II, three-arm, randomised, double-blind, multicentre trial with a semifactorial design. Participants continued on trial treatment for up to 24 months. Setting: Patients were identified from memory services, both within the 32 participating NHS trusts and within the network of memory services supported by the Dementias and Neurodegenerative Diseases Research Network (also known as DeNDRoN). Participants: Patients with standardised Mini Mental State Examination scores of > 23 points and with Alzheimer’s disease assessed by the National Institute on Aging–Alzheimer’s Association’s criteria were identified from memory services. Intervention: Patients with mild Alzheimer’s disease were randomly allocated 1 : 1 : 1 to receive one of three treatments: arm 1 – 400 mg per day of minocycline; arm 2 – 200 mg per day of minocycline; or arm 3 – placebo. Patients continued treatment for 24 months. Participants, investigators and outcome assessors were blind to treatment allocation. Main outcome measures: Primary outcome measures were decline in standardised Mini Mental State Examination and Bristol Activities of Daily Living Scale scores of combined minocycline treatment arms versus placebo, as analysed by intention-to-treat repeated measures regression. Results: Between 23 May 2014 and 14 April 2016, 554 participants were randomised. Of the 544 eligible participants, the mean age was 74.3 years and the average standardised Mini Mental State Examination score was 26.4 points. A total of 252 serious adverse events were reported, with the most common categories being neuropsychiatric and cardiocirculatory. Significantly fewer participants completed treatment with 400 mg of minocycline [29% (53/184)] than 200 mg [62% (112/181)] or placebo [64% (114/179)] (p < 0.0001), mainly because of gastrointestinal symptoms (p = 0.0008), dermatological side effects (p = 0.02) and dizziness (p = 0.01). Assessment rates were also lower in the 400-mg treatment arm: 68% (119 of 174 expected) for standardised Mini Mental State Examination scores at 24 months, compared with 82% (144/176) for the 200-mg treatment arm and 84% (140/167) for the placebo arm. Decline in standardised Mini Mental State Examination scores over the 24-month study period in the combined minocycline arms was similar to that in the placebo arm (4.1- vs. 4.3-point reduction; p = 0.9), as was the decline in the 400- and 200-mg treatment arms (3.3 vs. 4.7 points; p = 0.08). Likewise, worsening of Bristol Activities of Daily Living Scale scores over 24 months was similar in all trial arms (5.7, 6.6 and 6.2 points in the 400-mg treatment arm, 200-mg treatment arm and placebo arm, respectively; a p-value of 0.57 for minocycline vs. placebo and a p-value of 0.77 for 400 vs. 200 mg of minocycline). Results were similar in different patient subgroups and in sensitivity analyses adjusting for missing data. Limitations: Potential limitations of the study include that biomarkers were not used to confirm the diagnosis of Alzheimer’s disease, as these and apolipoprotein E (APOE) genotyping are not routinely available within the NHS. Compliance was also worse than expected and differential follow-up rates were observed, with fewer assessments obtained for the 400-mg treatment arm than for the 200-mg treatment and placebo arms. Conclusions: Minocycline does not delay the progress of cognitive or functional impairment in people with mild Alzheimer’s disease over a 2-year period. Minocycline at a dose of 400 mg is poorly tolerated in this population. Future work: The Minocycline in mild Alzheimer’s DiseasE (MADE) study provides a framework for a streamlined trial design that can be usefully applied to test other disease-modifying therapies

A highly conserved complete accessory Escherichia coli type III secretion system 2 is widespread in bloodstream isolates of the ST69 lineage

The work was funded by the Scottish Executive via the Chief Scientists Office through the provision of a grant to establish the Scottish Healthcare Associated Infection Prevention Institute (SHAIPI). The funders had no role in the study design, data collection and interpretation, or the decision to submit the work for publication.Bacterial type III secretion systems (T3SSs) play an important role in pathogenesis of Gram-negative infections. Enteropathogenic and enterohemorrhagic Escherichia coli contain a well-defined T3SS but in addition a second T3SS termed E. coli T3SS 2 (ETT2) has been described in a number of strains of E. coli. The majority of pathogenic E. coli contain elements of a genetic locus encoding ETT2, but which has undergone significant mutational attrition rendering it without predicted function. Only a very few strains have been reported to contain an intact ETT2 locus. To investigate the occurrence of the ETT2 locus in strains of human pathogenic E. coli, we carried out genomic sequencing of 162 isolates obtained from patient blood cultures in Scotland. We found that 22 of 26 sequence type (ST) 69 isolates from this collection contained an intact ETT2 together with an associated eip locus which encodes putative secreted ETT2 effectors as well as eilA, a gene encoding a putative transcriptional regulator of ETT2 associated genes. Using a reporter gene for eilA activation, we defined conditions under which this gene was differentially activated. Analysis of published E. coli genomes with worldwide representation showed that ST69 contained an intact ETT2 in these strains as well. The conservation of the genes encoding ETT2 in human pathogenic ST69 strains strongly suggests it has importance in infection, although its exact functional role remains obscure.Publisher PDFPeer reviewe

Cost-effectiveness analyses for mirtazapine and sertraline in dementia: randomised controlled trial

BACKGROUND Depression is a common and costly comorbidity in dementia. There are very few data on the cost-effectiveness of antidepressants for depression in dementia and their effects on carer outcomes. AIMS To evaluate the cost-effectiveness of sertraline and mirtazapine compared with placebo for depression in dementia. METHOD A pragmatic, multicentre, randomised placebo-controlled trial with a parallel cost-effectiveness analysis (trial registration: ISRCTN88882979 and EudraCT 2006-000105-38). The primary cost-effectiveness analysis compared differences in treatment costs for patients receiving sertraline, mirtazapine or placebo with differences in effectiveness measured by the primary outcome, total Cornell Scale for Depression in Dementia (CSDD) score, over two time periods: 0-13 weeks and 0-39 weeks. The secondary evaluation was a cost-utility analysis using quality-adjusted life years (QALYs) computed from the Euro-Qual (EQ-5D) and societal weights over those same periods. RESULTS There were 339 participants randomised and 326 with costs data (111 placebo, 107 sertraline, 108 mirtazapine). For the primary outcome, decrease in depression, mirtazapine and sertraline were not cost-effective compared with placebo. However, examining secondary outcomes, the time spent by unpaid carers caring for participants in the mirtazapine group was almost half that for patients receiving placebo (6.74 v. 12.27 hours per week) or sertraline (6.74 v. 12.32 hours per week). Informal care costs over 39 weeks were £1510 and £1522 less for the mirtazapine group compared with placebo and sertraline respectively. CONCLUSIONS In terms of reducing depression, mirtazapine and sertraline were not cost-effective for treating depression in dementia. However, mirtazapine does appear likely to have been cost-effective if costing includes the impact on unpaid carers and with quality of life included in the outcome. Unpaid (family) carer costs were lower with mirtazapine than sertraline or placebo. This may have been mediated via the putative ability of mirtazapine to ameliorate sleep disturbances and anxiety. Given the priority and the potential value of supporting family carers of people with dementia, further research is warranted to investigate the potential of mirtazapine to help with behavioural and psychological symptoms in dementia and in supporting carers