Excavating French Melodrama of the First Empire

This article offers a case study of how revivals of two early nineteenth-century French melodramas have enabled interdisciplinary dialogue on moving from the textual study of melodrama to historically informed performance. Bringing together the text, the score and acting allows us to gain a much better understanding of the ways in which these elements interacted., Piecing together clues about the play as a performance in the process of preparing for 21st-century historically informed staging is a task similar to that of an archaeologist reassembling an old pot from a handful of pieces. This metaphor of archaeology comes from Mike Pearson and Michael Shanks’ seminal text Theatre/Archaeology and James Mathieu, Introduction to Experimental Archeology : replicating past objects, behaviors and processes. Shanks and Pearson in particular highlight the centrality of interpretation in both archaeology and performance and see both spheres as connected by a common aim to retrieve and reconstruct ephemeral events and understand the textures of the social and cultural experience of the object in the past. Exploring the idea of archaeology as a metaphor for our work helped us reach a clearer understanding of text, music and genre in melodrama

Martial Women in the British Theatre, 1789-1804

In the period of the French Revolution, the armed or martial woman comes to stand in Britain as the representative of extreme political and social disruption. She embodies, in striking form, the revolutionary chaos witnessed across the channel, which threatens to infect British culture. This thesis traces shifting representations of the female warrior, and examines the complex processes by which the threat that she personifies is handled in British tragedies and sentimental comedies, written and performed in London and Dublin between 1789 and 1804. The study presents the British theatre as an arena in which the significance of the arms-bearing woman is constantly re-modelled and re-appropriated to fulfil diverse ideological functions. Used to challenge as well as to enforce established notions of sex and gender difference, she is fashioned also as an allegorical tool, serving both to condemn and to champion political rebellion in England, France and Ireland. Combining close readings of dramatic texts with detailed discussions of production and performance histories, this thesis tells a story of the martial woman’s evolution in British dramas, which emphasises her multifaceted and protean identity, and shows her development not to have followed a stable or linear pattern, but to have been constantly redirected by an expansive range of contextual factors: historical, social, and theatrical

Comparison of aggregate and individual participant data approaches to meta-analysis of randomised trials : An observational study

BACKGROUND: It remains unclear when standard systematic reviews and meta-analyses that rely on published aggregate data (AD) can provide robust clinical conclusions. We aimed to compare the results from a large cohort of systematic reviews and meta-analyses based on individual participant data (IPD) with meta-analyses of published AD, to establish when the latter are most likely to be reliable and when the IPD approach might be required. METHODS AND FINDINGS: We used 18 cancer systematic reviews that included IPD meta-analyses: all of those completed and published by the Meta-analysis Group of the MRC Clinical Trials Unit from 1991 to 2010. We extracted or estimated hazard ratios (HRs) and standard errors (SEs) for survival from trial reports and compared these with IPD equivalents at both the trial and meta-analysis level. We also extracted or estimated the number of events. We used paired t tests to assess whether HRs and SEs from published AD differed on average from those from IPD. We assessed agreement, and whether this was associated with trial or meta-analysis characteristics, using the approach of Bland and Altman. The 18 systematic reviews comprised 238 unique trials or trial comparisons, including 37,082 participants. A HR and SE could be generated for 127 trials, representing 53% of the trials and approximately 79% of eligible participants. On average, trial HRs derived from published AD were slightly more in favour of the research interventions than those from IPD (HRAD to HRIPD ratio = 0.95, p = 0.007), but the limits of agreement show that for individual trials, the HRs could deviate substantially. These limits narrowed with an increasing number of participants (p < 0.001) or a greater number (p < 0.001) or proportion (p < 0.001) of events in the AD. On average, meta-analysis HRs from published AD slightly tended to favour the research interventions whether based on fixed-effect (HRAD to HRIPD ratio = 0.97, p = 0.088) or random-effects (HRAD to HRIPD ratio = 0.96, p = 0.044) models, but the limits of agreement show that for individual meta-analyses, agreement was much more variable. These limits tended to narrow with an increasing number (p = 0.077) or proportion of events (p = 0.11) in the AD. However, even when the information size of the AD was large, individual meta-analysis HRs could still differ from their IPD equivalents by a relative 10% in favour of the research intervention to 5% in favour of control. We utilised the results to construct a decision tree for assessing whether an AD meta-analysis includes sufficient information, and when estimates of effects are most likely to be reliable. A lack of power at the meta-analysis level may have prevented us identifying additional factors associated with the reliability of AD meta-analyses, and we cannot be sure that our results are generalisable to all outcomes and effect measures. CONCLUSIONS: In this study we found that HRs from published AD were most likely to agree with those from IPD when the information size was large. Based on these findings, we provide guidance for determining systematically when standard AD meta-analysis will likely generate robust clinical conclusions, and when the IPD approach will add considerable value

Quantification of habitat fragmentation reveals extinction risk in terrestrial mammals

Although habitat fragmentation is often assumed to be a primary driver of extinction, global patterns of fragmentation and its relationship to extinction risk have not been consistently quantified for any major animal taxon. We developed high-resolution habitat fragmentation models and used phylogenetic comparative methods to quantify the effects of habitat fragmentation on the world's terrestrial mammals, including 4,018 species across 26 taxonomic Orders. Results demonstrate that species with more fragmentation are at greater risk of extinction, even after accounting for the effects of key macroecological predictors, such as body size and geographic range size. Species with higher fragmentation had smaller ranges and a lower proportion of high-suitability habitat within their range, andmost high-suitability habitat occurred outside of protected areas, further elevating extinction risk. Our models provide a quantitative evaluation of extinction risk assessments for species, allow for identification of emerging threats in species not classified as threatened, and provide maps of global hotspots of fragmentation for the world's terrestrial mammals. Quantification of habitat fragmentation will help guide threat assessment and strategic priorities for global mammal conservation

Impact of paternal deployment to the conflicts in Iraq and Afghanistan and paternal post-traumatic stress disorder on the children of military fathers

Background Little is known about the social and emotional well-being of children whose fathers have been deployed to the conflicts in Iraq/ Afghanistan or who have post-traumatic stress disorder (PTSD). Aims To examine the emotional and behavioural well-being of children whose fathers are or have been in the UK armed forces, in particular the effects of paternal deployment to the conflicts in Iraq or Afghanistan and paternal PTSD. Method Fathers who had taken part in a large tri-service cohort and had children aged 3–16 years were asked about the emotional and behavioural well-being of their child(ren) and assessed for symptoms of PTSD via online questionnaires and telephone interview. Results In total, 621 (67%) fathers participated, providing data on 1044 children. Paternal deployment to Iraq or Afghanistan was not associated with childhood emotional and behavioural difficulties. Paternal probable PTSD were associated with child hyperactivity. This finding was limited to boys and those under 11 years of age. Conclusions This study showed that adverse childhood emotional and behavioural well-being was not associated with paternal deployment but was associated with paternal probable PTSD

Which patients with metastatic hormone-sensitive prostate cancer benefit from docetaxel: a systematic review and meta-analysis of individual participant data from randomised trials

BACKGROUND: Adding docetaxel to androgen deprivation therapy (ADT) improves survival in patients with metastatic, hormone-sensitive prostate cancer, but uncertainty remains about who benefits most. We therefore aimed to obtain up-to-date estimates of the overall effects of docetaxel and to assess whether these effects varied according to prespecified characteristics of the patients or their tumours. METHODS: The STOPCAP M1 collaboration conducted a systematic review and meta-analysis of individual participant data. We searched MEDLINE (from database inception to March 31, 2022), Embase (from database inception to March 31, 2022), the Cochrane Central Register of Controlled Trials (from database inception to March 31, 2022), proceedings of relevant conferences (from Jan 1, 1990, to Dec 31, 2022), and ClinicalTrials.gov (from database inception to March 28, 2023) to identify eligible randomised trials that assessed docetaxel plus ADT compared with ADT alone in patients with metastatic, hormone-sensitive prostate cancer. Detailed and updated individual participant data were requested directly from study investigators or through relevant repositories. The primary outcome was overall survival. Secondary outcomes were progression-free survival and failure-free survival. Overall pooled effects were estimated using an adjusted, intention-to-treat, two-stage, fixed-effect meta-analysis, with one-stage and random-effects sensitivity analyses. Missing covariate values were imputed. Differences in effect by participant characteristics were estimated using adjusted two-stage, fixed-effect meta-analysis of within-trial interactions on the basis of progression-free survival to maximise power. Identified effect modifiers were also assessed on the basis of overall survival. To explore multiple subgroup interactions and derive subgroup-specific absolute treatment effects we used one-stage flexible parametric modelling and regression standardisation. We assessed the risk of bias using the Cochrane Risk of Bias 2 tool. This study is registered with PROSPERO, CRD42019140591. FINDINGS: We obtained individual participant data from 2261 patients (98% of those randomised) from three eligible trials (GETUG-AFU15, CHAARTED, and STAMPEDE trials), with a median follow-up of 72 months (IQR 55-85). Individual participant data were not obtained from two additional small trials. Based on all included trials and patients, there were clear benefits of docetaxel on overall survival (hazard ratio [HR] 0·79, 95% CI 0·70 to 0·88; p<0·0001), progression-free survival (0·70, 0·63 to 0·77; p<0·0001), and failure-free survival (0·64, 0·58 to 0·71; p<0·0001), representing 5-year absolute improvements of around 9-11%. The overall risk of bias was assessed to be low, and there was no strong evidence of differences in effect between trials for all three main outcomes. The relative effect of docetaxel on progression-free survival appeared to be greater with increasing clinical T stage (pinteraction=0·0019), higher volume of metastases (pinteraction=0·020), and, to a lesser extent, synchronous diagnosis of metastatic disease (pinteraction=0·077). Taking into account the other interactions, the effect of docetaxel was independently modified by volume and clinical T stage, but not timing. There was no strong evidence that docetaxel improved absolute effects at 5 years for patients with low-volume, metachronous disease (-1%, 95% CI -15 to 12, for progression-free survival; 0%, -10 to 12, for overall survival). The largest absolute improvement at 5 years was observed for those with high-volume, clinical T stage 4 disease (27%, 95% CI 17 to 37, for progression-free survival; 35%, 24 to 47, for overall survival). INTERPRETATION: The addition of docetaxel to hormone therapy is best suited to patients with poorer prognosis for metastatic, hormone-sensitive prostate cancer based on a high volume of disease and potentially the bulkiness of the primary tumour. There is no evidence of meaningful benefit for patients with metachronous, low-volume disease who should therefore be managed differently. These results will better characterise patients most and, importantly, least likely to gain benefit from docetaxel, potentially changing international practice, guiding clinical decision making, better informing treatment policy, and improving patient outcomes. FUNDING: UK Medical Research Council and Prostate Cancer UK

Adjuvant Chemotherapy for Muscle-invasive Bladder Cancer : A Systematic Review and Meta-analysis of Individual Participant Data from Randomised Controlled Trials

Context Our prior systematic review and meta-analysis of individual participant data (IPD) suggesting a benefit of adjuvant chemotherapy for muscle-invasive bladder cancer was limited by the number and size of included randomised trials. We have updated results to include additional trials, providing the most up-to-date and reliable evidence of the effects of this treatment. Objective To investigate the role of adjuvant cisplatin-based chemotherapy in the treatment of muscle-invasive bladder cancer. Evidence acquisition Published and unpublished trials were sought via searches of bibliographic databases, trials registers, conference proceedings, and hand searching. Updated IPD were centrally collected, checked, and analysed. Results from individual randomised controlled trials (RCTs) were combined using a two-stage fixed-effect model. Prespecified analyses explored any variation in effect by trial and participant characteristics. Evidence synthesis Analyses of ten RCTs (1183 participants) demonstrated a benefit of cisplatin-based adjuvant chemotherapy on overall survival (hazard ratio [HR] = 0.82, 95% confidence interval [CI] = 0.70–0.96, p = 0.02). This represents an absolute improvement in survival of 6% at 5 yr, from 50% to 56%, and a 9% absolute benefit when adjusted for age, sex, pT stage, and pN category (HR = 0.77, 95% CI = 0.65–0.92, p = 0.004). There was no clear evidence that the effect varied by trial or participant characteristics. Adjuvant chemotherapy was also shown to improve recurrence-free survival (HR = 0.71, 95% CI = 0.60–0.83, p < 0.001), locoregional recurrence-free survival (HR = 0.68, 95% CI = 0.55–0.85, p < 0.001), and metastasis-free survival (HR = 0.79, 95% CI = 0.65–0.95, p = 0.01), with absolute benefits of 11%, 11%, and 8%, respectively. Conclusions This systematic review and meta-analysis demonstrates that cisplatin-based adjuvant chemotherapy is a valid option for improving outcomes for muscle-invasive bladder cancer. Patient summary We looked at the effect of cisplatin-based chemotherapy on outcomes in participants with muscle-invasive bladder cancer. We gathered this information from eligible randomised controlled trials. We demonstrated that cisplatin-based chemotherapy is a valid option for improving outcomes of muscle-invasive bladder cancer