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Jameson argues that in 'a society bereft of all historicity', 'what used to be the historical novel can no longer set out to represent the historical past'. The 'postmodern fate' of the historical novel is to be forced to come to terms with 'a new and original historical situation in which we are condemned to seek History by way of our own pop images and simulacra of that history, which itself remains forever out of reach. Salman Rushdie's "Midnight's Children" (1981) and Patrick Süskind's "Das Parfum. Die Geschichte eines Mörders" (1984) stand out as two hugely successful novels from this period that raise questions about historical representation within the space of the popular. They might therefore be used as test cases for Jameson's concerns. "Midnight's Children" is a sprawling story of Indian and British imperial and post-imperial history across the twentieth century. "Das Parfum" tells the tightly framed tale of a murderous perfumer in eighteenth-century France. Seemingly very different texts, they bear one curious similarity: both feature a protagonist with an unusually sensitive sense of smell.
In his article "The End of History?", originally published in the journal "The National Interest" in Summer 1989, Frances Fukuyama argued that 'the triumph of the West, of the Western idea, is evident first of all in the total exhaustion of viable systemic alternatives to Western liberalism.' It was in this respect that history had reached its 'end': the course of history in the sense of 'mankind's logical evolution' had arrived at 'the universalization of Western liberal democracy as the final form of human government'. [...] A look at some of the historical fiction written in the 1980s might suggest ways out of this potential imaginative impasse, offering up alternative possibilities, or 'Gegenwelten', in place of the dispiriting spectacle of history-on-repeat. Fukuyama himself does not mention literature. In fact, the historical fiction of the 1980s reveals a space in which the meaning of 'history' is still very much contested and where the threat of the 'end of history' in its more obvious sense - in the form of nuclear war or climate apocalypse - emerges as a force that speaks powerfully to the anxiety of our present moment. Two evocative novels that have much to tell us in these respects are Christa Wolf's "Kassandra" and Jeanette Winterson's "Sexing the Cherry". Published in 1984 and 1989, these two texts challenged the idea of rational progress and 'mankind's logical evolution' by raising the prospect of a distinctive feminist poetics - of 'écriture féminine' and 'what it will do' as Hélène Cixous had put it in her 1975 essay "The Laugh of the Medusa". The 'Gegenwelten' they propose suggest ways out of the macho strait jacket of violence, destruction and impending nuclear war.
Background: Effective inhibition of plasma kallikrein may have significant benefits for patients with hereditary angioedema due to deficiency of C1 inhibitor (C1‐INH‐HAE) by reducing the frequency of angioedema attacks. Avoralstat is a small molecule inhibitor of plasma kallikrein. This study (OPuS‐2) evaluated the efficacy and safety of prophylactic avoralstat 300 or 500 mg compared with placebo.
Methods: OPuS‐2 was a Phase 3, multicenter, randomized, double‐blind, placebo‐controlled, parallel‐group study. Subjects were administered avoralstat 300 mg, avoralstat 500 mg, or placebo orally 3 times per day for 12 weeks. The primary efficacy endpoint was the angioedema attack rate based on adjudicator‐confirmed attacks.
Results: A total of 110 subjects were randomized and dosed. The least squares (LS) mean attack rates per week were 0.589, 0.675, and 0.593 for subjects receiving avoralstat 500 mg, avoralstat 300 mg, and placebo, respectively. Overall, 1 subject in each of the avoralstat groups and no subjects in the placebo group were attack‐free during the 84‐day treatment period. The LS mean duration of all confirmed attacks was 25.4, 29.4, and 31.4 hours for the avoralstat 500 mg, avoralstat 300 mg, and placebo groups, respectively. Using the Angioedema Quality of Life Questionnaire (AE‐QoL), improved QoL was observed for the avoralstat 500 mg group compared with placebo. Avoralstat was generally safe and well tolerated.
Conclusions: Although this study did not demonstrate efficacy of avoralstat in preventing angioedema attacks in C1‐INH‐HAE, it provided evidence of shortened angioedema episodes and improved QoL in the avoralstat 500 mg treatment group compared with placebo.
Background: Intracerebral haemorrhage growth is associated with poor clinical outcome and is a therapeutic target for improving outcome. We aimed to determine the absolute risk and predictors of intracerebral haemorrhage growth, develop and validate prediction models, and evaluate the added value of CT angiography.
Methods: In a systematic review of OVID MEDLINE—with additional hand-searching of relevant studies' bibliographies— from Jan 1, 1970, to Dec 31, 2015, we identified observational cohorts and randomised trials with repeat scanning protocols that included at least ten patients with acute intracerebral haemorrhage. We sought individual patient-level data from corresponding authors for patients aged 18 years or older with data available from brain imaging initially done 0·5–24 h and repeated fewer than 6 days after symptom onset, who had baseline intracerebral haemorrhage volume of less than 150 mL, and did not undergo acute treatment that might reduce intracerebral haemorrhage volume. We estimated the absolute risk and predictors of the primary outcome of intracerebral haemorrhage growth (defined as >6 mL increase in intracerebral haemorrhage volume on repeat imaging) using multivariable logistic regression models in development and validation cohorts in four subgroups of patients, using a hierarchical approach: patients not taking anticoagulant therapy at intracerebral haemorrhage onset (who constituted the largest subgroup), patients taking anticoagulant therapy at intracerebral haemorrhage onset, patients from cohorts that included at least some patients taking anticoagulant therapy at intracerebral haemorrhage onset, and patients for whom both information about anticoagulant therapy at intracerebral haemorrhage onset and spot sign on acute CT angiography were known.
Findings: Of 4191 studies identified, 77 were eligible for inclusion. Overall, 36 (47%) cohorts provided data on 5435 eligible patients. 5076 of these patients were not taking anticoagulant therapy at symptom onset (median age 67 years, IQR 56–76), of whom 1009 (20%) had intracerebral haemorrhage growth. Multivariable models of patients with data on antiplatelet therapy use, data on anticoagulant therapy use, and assessment of CT angiography spot sign at symptom onset showed that time from symptom onset to baseline imaging (odds ratio 0·50, 95% CI 0·36–0·70; p<0·0001), intracerebral haemorrhage volume on baseline imaging (7·18, 4·46–11·60; p<0·0001), antiplatelet use (1·68, 1·06–2·66; p=0·026), and anticoagulant use (3·48, 1·96–6·16; p<0·0001) were independent predictors of intracerebral haemorrhage growth (C-index 0·78, 95% CI 0·75–0·82). Addition of CT angiography spot sign (odds ratio 4·46, 95% CI 2·95–6·75; p<0·0001) to the model increased the C-index by 0·05 (95% CI 0·03–0·07).
Interpretation: In this large patient-level meta-analysis, models using four or five predictors had acceptable to good discrimination. These models could inform the location and frequency of observations on patients in clinical practice, explain treatment effects in prior randomised trials, and guide the design of future trials.
Funding: UK Medical Research Council and British Heart Foundation.
We present the first measurements of charge-dependent correlations on angular difference variables η1 − η2 (pseudorapidity) and φ1 − φ2 (azimuth) for primary charged hadrons with transverse momentum 0.15 <= pt <= 2 GeV/c and |η| <= 1.3 from Au–Au collisions at √sNN = 130 GeV. We observe correlation structures not predicted by theory but consistent with evolution of hadron emission geometry with increasing centrality from one-dimensional fragmentation of color strings along the beam direction to an at least two-dimensional hadronization geometry along the beam and azimuth directions of a hadron-opaque bulk medium.