2,036 research outputs found

    The genealogy of judgement: towards a deep history of academic freedom

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    The classical conception of academic freedom associated with Wilhelm von Humboldt and the rise of the modern university has a quite specific cultural foundation that centres on the controversial mental faculty of 'judgement'. This article traces the roots of 'judgement' back to the Protestant Reformation, through its heyday as the signature feature of German idealism, and to its gradual loss of salience as both a philosophical and a psychological concept. This trajectory has been accompanied by a general shrinking in the scope of academic freedom from the promulgation of world-views to the offering of expert opinion

    Para-cresol production by Clostridium difficile affects microbial diversity and membrane integrity of Gram-negative bacteria

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    Clostridium difficile is a Gram-positive spore-forming anaerobe and a major cause of antibiotic-associated diarrhoea. Disruption of the commensal microbiota, such as through treatment with broad-spectrum antibiotics, is a critical precursor for colonisation by C. difficile and subsequent disease. Furthermore, failure of the gut microbiota to recover colonisation resistance can result in recurrence of infection. An unusual characteristic of C. difficile among gut bacteria is its ability to produce the bacteriostatic compound para-cresol (p-cresol) through fermentation of tyrosine. Here, we demonstrate that the ability of C. difficile to produce p-cresol in vitro provides a competitive advantage over gut bacteria including Escherichia coli, Klebsiella oxytoca and Bacteroides thetaiotaomicron. Metabolic profiling of competitive co-cultures revealed that acetate, alanine, butyrate, isobutyrate, p-cresol and p-hydroxyphenylacetate were the main metabolites responsible for differentiating the parent strain C. difficile (630Δerm) from a defined mutant deficient in p-cresol production. Moreover, we show that the p-cresol mutant displays a fitness defect in a mouse relapse model of C. difficile infection (CDI). Analysis of the microbiome from this mouse model of CDI demonstrates that colonisation by the p-cresol mutant results in a distinctly altered intestinal microbiota, and metabolic profile, with a greater representation of Gammaproteobacteria, including the Pseudomonales and Enterobacteriales. We demonstrate that Gammaproteobacteria are susceptible to exogenous p-cresol in vitro and that there is a clear divide between bacterial Phyla and their susceptibility to p-cresol. In general, Gram-negative species were relatively sensitive to p-cresol, whereas Gram-positive species were more tolerant. This study demonstrates that production of p-cresol by C. difficile has an effect on the viability of intestinal bacteria as well as the major metabolites produced in vitro. These observations are upheld in a mouse model of CDI, in which p-cresol production affects the biodiversity of gut microbiota and faecal metabolite profiles, suggesting that p-cresol production contributes to C. difficile survival and pathogenesis.Peer reviewedFinal Published versio

    Rethinking the social impacts of the arts

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    The paper presents a critical discussion of the current debate over the social impacts of the arts in the UK. It argues that the accepted understanding of the terms of the debate is rooted in a number of assumptions and beliefs that are rarely questioned. The paper goes on to present the interim findings of a three‐year research project, which aims to rethink the social impact of the arts, with a view to determining how these impacts might be better understood. The desirability of a historical approach is articulated, and a classification of the claims made within the Western intellectual tradition for what the arts “do” to people is presented and discussed

    Stoics against stoics in Cudworth's "A Treatise of Freewill"

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    In his 'A Treatise of Freewill', Ralph Cudworth argues against Stoic determinism by drawing on what he takes to be other concepts found in Stoicism, notably the claim that some things are ‘up to us’ and that these things are the product of our choice. These concepts are central to the late Stoic Epictetus and it appears at first glance as if Cudworth is opposing late Stoic voluntarism against early Stoic determinism. This paper argues that in fact, despite his claim to be drawing on Stoic doctrine, Cudworth uses these terms with a meaning first articulated only later, by the Peripatetic commentator Alexander of Aphrodisias

    Atomic mass dependence of \Xi^- and \overline{\Xi}^+ production in central 250 GeV \pi^- nucleon interactions

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    We present the first measurement of the atomic mass dependence of central \Xi^- and \overline{\Xi}^+ production. It is measured using a sample of 22,459 \Xi^-'s and \overline{\Xi}^+'s produced in collisions between a 250 GeV \pi^- beam and targets of beryllium, aluminum, copper, and tungsten. The relative cross sections are fit to the two parameter function \sigma_0 A^\alpha, where A is the atomic mass. We measure \alpha = 0.924+-0.020+-0.025, for Feynman-x in the range -0.09 < x_F < 0.15.Comment: 10 pages, revtex, 2 figures, submitted to Phys. Rev.

    Parental bonding and identity style as correlates of self-esteem among adult adoptees and nonadoptees

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    Adult adoptees (n equals 100) and non-adoptees (n equals 100) were compared with regard to selfesteem, identity processing style, and parental bonding. While some differences were found with regard to self-esteem, maternal care, and maternal overprotection, these differences were qualified by reunion status such that only reunited adoptees differed significantly from nonadoptees. Moreover, hierarchical regression analyses indicated that parental bonding and identity processing style were more important than adoptive status per se in predicting self esteem. Implications for practitioners who work with adoptees are discussed

    A Single-Arm, Proof-Of-Concept Trial of Lopimune (Lopinavir/Ritonavir) as a Treatment for HPV-Related Pre-Invasive Cervical Disease

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    BACKGROUND: Cervical cancer is the most common female malignancy in the developing nations and the third most common cancer in women globally. An effective, inexpensive and self-applied topical treatment would be an ideal solution for treatment of screen-detected, pre-invasive cervical disease in low resource settings. METHODS: Between 01/03/2013 and 01/08/2013, women attending Kenyatta National Hospital's Family Planning and Gynaecology Outpatients clinics were tested for HIV, HPV (Cervista®) and liquid based cervical cytology (LBC -ThinPrep®). HIV negative women diagnosed as high-risk HPV positive with high grade squamous intraepithelial lesions (HSIL) were examined by colposcopy and given a 2 week course of 1 capsule of Lopimune (CIPLA) twice daily, to be self-applied as a vaginal pessary. Colposcopy, HPV testing and LBC were repeated at 4 and 12 weeks post-start of treatment with a final punch biopsy at 3 months for histology. Primary outcome measures were acceptability of treatment with efficacy as a secondary consideration. RESULTS: A total of 23 women with HSIL were treated with Lopimune during which time no adverse reactions were reported. A maximum concentration of 10 ng/ml of lopinavir was detected in patient plasma 1 week after starting treatment. HPV was no longer detected in 12/23 (52.2%, 95%CI: 30.6-73.2%). Post-treatment cytology at 12 weeks on women with HSIL, showed 14/22 (63.6%, 95%CI: 40.6-82.8%) had no dysplasia and 4/22 (18.2%, 95%CI: 9.9-65.1%) were now low grade demonstrating a combined positive response in 81.8% of women of which 77.8% was confirmed by histology. These data are supported by colposcopic images, which show regression of cervical lesions. CONCLUSIONS: These results demonstrate the potential of Lopimune as a self-applied therapy for HPV infection and related cervical lesions. Since there were no serious adverse events or detectable post-treatment morbidity, this study indicates that further trials are clearly justified to define optimal regimes and the overall benefit of this therapy. TRIAL REGISTRATION: ISRCTN Registry 48776874
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