60 research outputs found

    Résurgences nationalistes et divergences politiques : quel avenir pour l'Union britannique

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    Ce document sera publié en ligne en texte intégral en mars 2012: http://etudesecossaises.revues.org/index363.htmlTen years after the 1997 Scottish and Welsh referenda, Plaid Cymru and the SNP both became parties of government in their respective nations. The vast majority of the Welsh and Scottish populations today are in favour of the extension of powers of the Scottish Parliament and the National Assembly of Wales. Both governments have indeed agreed to organize new referenda on the political and constitutional future of their institutions before the 2011 Scottish and Welsh general elections. The development of Welsh and Scottish politics since 1999 is therefore contrary to the Labour Party's expectations as it wished to curb nationalism by implementing devolution. Indeed, the new political institutions have succeeded in forging their own political identities and have, sometimes drastically, moved away from Westminster's style and politics, as illustrated by the debates on health and higher education."Dix ans seulement après les référendums de 1997 pour la création de nouvelles institutions politiques en Écosse et au pays de Galles, Plaid Cymru et le SNP accédaient tous deux aux gouvernements de leurs nations respectives. Aujourd'hui la majorité des Gallois et des Écossais souhaitent l'élargissement des pouvoirs de leurs arènes politiques et les gouvernements gallois et écossais prévoient tous deux l'organisation de nouveaux référendums sur l'avenir constitutionnel ou politique des nouvelles institutions avant les élections législatives de 2011. L'évolution des événements politiques en Écosse et au pays de Galles est ainsi contraire aux attentes du Parti travailliste britannique qui souhaitait enrayer la progression du nationalisme par la dévolution. En effet, les nouvelles institutions ont su au fil du temps créer leurs propres identités politiques et se démarquer, parfois distinctement, du style politique de Westminster et des politiques du gouvernement britannique. C'est ce qu'illustreront tout particulièrement les débats sur les questions de santé et d'enseignement supérieur. Resurgent Nationalisms: What Future for the United Kingdom?" Ce document sera publié en ligne en texte intégral en mars 2012: http://etudesecossaises.revues.org/index363.htm

    Interview with Alan Gibbons, Labour Party Activist

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    Alan Gibbons is a member of Liverpool Walton Constituency Labour Party. He writes adult and children’s fiction and is about to start work on a history of the Left in Liverpool. Alan Gibbons is a million-selling writer of over seventy books. He decided to join the Labour Party in 2015, and was involved in the 2017 campaign. Q: How long have you been a member of the Labour Party? I joined the Labour Party three years ago, inspired by the campaign to elect Jeremy Corbyn. Q: Why did you join in..

    Induction of \u3cem\u3eIL19\u3c/em\u3e Expression through JNK and cGAS-STING Modulates DNA Damage–Induced Cytokine Production

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    Cytokine production is a critical component of cell-extrinsic responses to DNA damage and cellular senescence. Here, we demonstrated that expression of the gene encoding interleukin-19 (IL-19) was enhanced by DNA damage through pathways mediated by c-Jun amino-terminal kinase (JNK) and cGAS-STING and that IL19 expression was required for the subsequent production of the cytokines IL-1, IL-6, and IL-8. IL19 expression was stimulated by diverse cellular stresses, including inhibition of the DNA replication checkpoint kinase ATR (ataxia telangiectasia and Rad3-related protein), oncogene expression, replicative exhaustion, oxidative stress, and DNA double-strand breaks. Unlike the production of IL-6 and IL-8, IL19 expression was not affected by abrogation of signaling by the IL-1 receptor (IL-1R) or the mitogen-activated protein kinase p38. Instead, the DNA damage–induced production of IL-1, IL-6, and IL-8 was substantially reduced by suppression of IL19 expression. The signaling pathways required to stimulate IL19 expression selectively depended on the type of DNA-damaging agent. Reactive oxygen species and the ASK1-JNK pathway were critical for responses to ionizing radiation (IR), whereas the cGAS-STING pathway stimulated IL19 expression in response to either IR or ATR inhibition. Whereas induction of IL1, IL6, and IL8 by IR depended on IL19 expression, the cGAS-STING–dependent induction of the immune checkpoint gene PDL1 after IR and ATR inhibition was independent of IL19. Together, these results suggest that IL-19 production by diverse pathways forms a distinct cytokine regulatory arm of the response to DNA damage

    Nuclear envelope structural defects cause chromosomal numerical instability and aneuploidy in ovarian cancer

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    <p>Abstract</p> <p>Background</p> <p>Despite our substantial understanding of molecular mechanisms and gene mutations involved in cancer, the technical approaches for diagnosis and prognosis of cancer are limited. In routine clinical diagnosis of cancer, the procedure is very basic: nuclear morphology is used as a common assessment of the degree of malignancy, and hence acts as a prognostic and predictive indicator of the disease. Furthermore, though the atypical nuclear morphology of cancer cells is believed to be a consequence of oncogenic signaling, the molecular basis remains unclear. Another common characteristic of human cancer is aneuploidy, but the causes and its role in carcinogenesis are not well established.</p> <p>Methods</p> <p>We investigated the expression of the nuclear envelope proteins lamin A/C in ovarian cancer by immunohistochemistry and studied the consequence of lamin A/C suppression using siRNA in primary human ovarian surface epithelial cells in culture. We used immunofluorescence microscopy to analyze nuclear morphology, flow cytometry to analyze cellular DNA content, and fluorescence <it>in situ </it>hybridization to examine cell ploidy of the lamin A/C-suppressed cells.</p> <p>Results</p> <p>We found that nuclear lamina proteins lamin A/C are often absent (47%) in ovarian cancer cells and tissues. Even in lamin A/C-positive ovarian cancer, the expression is heterogeneous within the population of tumor cells. In most cancer cell lines, a significant fraction of the lamin A/C-negative population was observed to intermix with the lamin A/C-positive cells. Down regulation of lamin A/C in non-cancerous primary ovarian surface epithelial cells led to morphological deformation and development of aneuploidy. The aneuploid cells became growth retarded due to a p53-dependent induction of the cell cycle inhibitor p21.</p> <p>Conclusions</p> <p>We conclude that the loss of nuclear envelope structural proteins, such as lamin A/C, may underlie two of the hallmarks of cancer - aberrations in nuclear morphology and aneuploidy.</p

    Clinical outcomes and response to treatment of patients receiving topical treatments for pyoderma gangrenosum: a prospective cohort study

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    Background: pyoderma gangrenosum (PG) is an uncommon dermatosis with a limited evidence base for treatment. Objective: to estimate the effectiveness of topical therapies in the treatment of PG. Methods: prospective cohort study of UK secondary care patients with a clinical diagnosis of PG suitable for topical treatment (recruited July 2009 to June 2012). Participants received topical therapy following normal clinical practice (mainly Class I-III topical corticosteroids, tacrolimus 0.03% or 0.1%). Primary outcome: speed of healing at 6 weeks. Secondary outcomes: proportion healed by 6 months; time to healing; global assessment; inflammation; pain; quality-of-life; treatment failure and recurrence. Results: Sixty-six patients (22 to 85 years) were enrolled. Clobetasol propionate 0.05% was the most commonly prescribed therapy. Overall, 28/66 (43.8%) of ulcers healed by 6 months. Median time-to-healing was 145 days (95% CI: 96 days, ∞). Initial ulcer size was a significant predictor of time-to-healing (hazard ratio 0.94 (0.88;80 1.00); p = 0.043). Four patients (15%) had a recurrence. Limitations: No randomised comparator Conclusion: Topical therapy is potentially an effective first-line treatment for PG that avoids possible side effects associated with systemic therapy. It remains unclear whether more severe disease will respond adequately to topical therapy alone

    Silk garments plus standard care compared with standard care for treating eczema in children: A randomised, controlled, observer-blind, pragmatic trial (CLOTHES Trial)

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    © 2017 Thomas et al. Background: The role of clothing in the management of eczema (also called atopic dermatitis or atopic eczema) is poorly understood. This trial evaluated the effectiveness and cost-effectiveness of silk garments (in addition to standard care) for the management of eczema in children with moderate to severe disease. Methods and findings: This was a parallel-group, randomised, controlled, observer-blind trial. Children aged 1 to 15 y with moderate to severe eczema were recruited from secondary care and the community at five UK medical centres. Participants were allocated using online randomisation (1:1) to standard care or to standard care plus silk garments, stratified by age and recruiting centre. Silk garments were worn for 6 mo. Primary outcome (eczema severity) was assessed at baseline, 2, 4, and 6 mo, by nurses blinded to treatment allocation, using the Eczema Area and Severity Index (EASI), which was log-transformed for analysis (intention-to-treat analysis). A safety outcome was number of skin infections. Three hundred children were randomised (26 November 2013 to 5 May 2015): 42% girls, 79% white, mean age 5 y. Primary analysis included 282/300 (94%) children (n = 141 in each group). The garments were worn more often at night than in the day (median of 81% of nights [25th to 75th centile 57% to 96%] and 34% of days [25th to 75th centile 10% to 76%]). Geometric mean EASI scores at baseline, 2, 4, and 6 mo were, respectively, 9.2, 6.4, 5.8, and 5.4 for silk clothing and 8.4, 6.6, 6.0, and 5.4 for standard care. There was no evidence of any difference between the groups in EASI score averaged over all follow-up visits adjusted for baseline EASI score, age, and centre: adjusted ratio of geometric means 0.95, 95% CI 0.85 to 1.07, (p = 0.43). This confidence interval is equivalent to a difference of −1.5 to 0.5 in the original EASI units, which is not clinically important. Skin infections occurred in 36/142 (25%) and 39/141 (28%) of children in the silk clothing and standard care groups, respectively. Even if the small observed treatment effect was genuine, the incremental cost per quality-adjusted life year was £56,811 in the base case analysis from a National Health Service perspective, suggesting that silk garments are unlikely to be cost-effective using currently accepted thresholds. The main limitation of the study is that use of an objective primary outcome, whilst minimising detection bias, may have underestimated treatment effects. Conclusions: Silk clothing is unlikely to provide additional benefit over standard care in children with moderate to severe eczema. Trial registration: Current Controlled Trials ISRCTN77261365

    The association between treatment adherence to nicotine patches and smoking cessation in pregnancy: a secondary analysis of a randomised controlled trial

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    IntroductionIn non-pregnant ‘quitters’, adherence to nicotine replacement therapy (NRT) increases smoking cessation. We investigated relationships between adherence to placebo or NRT patches and cessation in pregnancy, including an assessment of reverse causation and whether any adherence: cessation relationship is moderated when using nicotine or placebo patches. MethodsUsing data from 1050 pregnant trial participants, regression models investigated associations between maternal characteristics, adherence and smoking cessation. ResultsAdherence during the first month was associated with lower baseline cotinine concentrations (beta -0.08, 95%CI -0.15 to -0.01) and randomisation to NRT (beta 2.59, 95%CI 1.50 to 3.68). Adherence during both treatment months was associated with being randomised to NRT (beta 0.51, 95%CI 0.29 to 0.72) and inversely associated with higher nicotine dependence. Adherence with either NRT or placebo was associated with cessation at one month (OR 1.11, 95%CI 1.08 to 1.13) and delivery (OR 1.06, 95%CI 1.03 to 1.09), but no such association was observed in the subgroup where reverse causation was not possible. Amongst all women, greater adherence to nicotine patches was associated with increased cessation (OR 2.47, 95%CI 1.32 to 4.63) but greater adherence to placebo was not (OR 0.98, 95%CI: 0.44 to 2.18). ConclusionWomen who were more adherent to NRT were more likely to achieve abstinence; more nicotine dependent women probably showed lower adherence to NRT because they relapsed to smoking more quickly. The interaction between nicotine-containing patches and adherence for cessation suggests that the association between adherence with nicotine patches and cessation may be partly causal

    Better Together and the No Campaign: from Project Fear to Grace?

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    Better Together was the main umbrella organisation of the No camp during the 2014 Scottish independence referendum campaign. It represented the common effort of three otherwise unlikely-minded British parties to work together and publicly collaborate to safeguard the Union. The difficulties that this collaboration represents were immense in that the three participating parties had distinct electoral and political histories in Scotland and each faced inner divisions and distinct challenges which this paper seeks to examine

    Parliamentary Practices in Holyrood: 'new Politics' and the SNP

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    International audienceThe Scottish Parliament was meant to represent a revolution in the way that Scots were governed as its supporters frequently expressed the hope that such a body would be a new type of institution that would represent a break with the Westminster model and would offer a new approach to the way that the business of government is carried on. The political arena that emerged out of the blueprint produced by the Scottish Constitutional Convention in the 1990s was the result of a historic consensus and was designed as a more inclusive, representative, transparent and collegial body which was to usher in 'new politics' for Scotland. This paper will therefore seek to examine to what extent the Scottish Constitutional Convention's initial goal of a more open, representative and participative approach to politics has been met and question the impact of its relative success on the surge of nationalism in Scotland
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