A socio-historical study of the treatment and reception of John Lydgate in Early Modern print culture

This project aims to explore the ways in which the works of late medieval poet John Lydgate are treated and received in their early printed forms. The study will chart the history and evolution of a selection of Lydgate texts through the late medieval and Reformation period, considering the texts and their reception in relation to the contemporary social, political and religious backdrop. The project will make special reference to the work of John Lydgate and evaluate his contemporary status as a high profile poet and his subsequent decline in popularity from the mid-sixteenth century. In order to provide a focus for the analysis of these texts, the punctuation practices employed by the various printers and editors will be studied in-depth in four of Lydgate’s texts; The Siege of Thebes, Troy Book, The Churl and the Bird and The Temple of Glas. This data will demonstrate the development of punctuation techniques in print from the late medieval to early modern period and determine how these techniques were applied to the chosen texts. The analysis of this data will further illustrate the changing requirements and expectations of the contemporary readership and the impact this had on the treatment and reception of Lydgate’s medieval texts. Despite his successful literary career during the fifteenth century, modern criticism has been harsh and Lydgate has long been considered a marginal figure in the canon of English literature. Scanlon and Simpson argue that this “was as much a matter of careful aesthetic discrimination as it was of historical reconstruction”; in other words, John Lydgate did not fit the literary and artistic ideals of the nineteenth century and was subsequently relegated to the margins of literary history (Scanlon & Simpson 2006: 2). More recently scholarship has aimed to take a fresh look at the life and work of John Lydgate and the influence he had on later writers and English literature as a whole. Attempting to sweep away the entrenched negative perceptions of his work as dull and didactic, scholars have begun to analyse Lydgate from a fifteenth-century perspective and to evaluate the role his work played in the lives and reading habits of late medieval England. As a definitively Catholic writer whose popularity spans the Reformation, it is Lydgate’s unique position which can provide insights into the contradictions and complexities of fifteenth century reading culture. His work is steeped in the medieval Catholic literary tradition, while also tackling contemporary political issues of kingship and national identity associated with the intellectual pursuits of the Renaissance. It is for this reason that Lydgate has been described as both a definitive embodiment of the middle ages (Pearsall 1970: 2) and as a “transition poet” (Renoir 1967: 31). Regardless of labelling, Lydgate was undoubtedly a central figure in fifteenth-century literary culture, and the treatment and reception of his texts can illustrate the ways in which sixteenth- and seventeenth-century editors, printers and publishers approached and dealt with late medieval texts while attempting to target a Renaissance audience amidst growing Protestant literature and propaganda. This project will determine how wider attitudinal changes and social shifts impacted the presentation of texts and the editing process, with particular reference to punctuation practices. Sixteenth-century England experienced significant social, religious and intellectual upheavals and this is clearly reflected in the reading habits and publishing trends of a rapidly expanding book industry. However, the central hypothesis of this dissertation argues that certain aspects of the editing process were less dramatic in their development. Punctuation practices in particular display a more gradual move towards modern conventions and represent the contradictions and complexities of a reading culture very much in transition

Effectiveness of a national quality improvement programme to improve survival after emergency abdominal surgery (EPOCH): a stepped-wedge cluster-randomised trial

Background: Emergency abdominal surgery is associated with poor patient outcomes. We studied the effectiveness of a national quality improvement (QI) programme to implement a care pathway to improve survival for these patients. Methods: We did a stepped-wedge cluster-randomised trial of patients aged 40 years or older undergoing emergency open major abdominal surgery. Eligible UK National Health Service (NHS) hospitals (those that had an emergency general surgical service, a substantial volume of emergency abdominal surgery cases, and contributed data to the National Emergency Laparotomy Audit) were organised into 15 geographical clusters and commenced the QI programme in a random order, based on a computer-generated random sequence, over an 85-week period with one geographical cluster commencing the intervention every 5 weeks from the second to the 16th time period. Patients were masked to the study group, but it was not possible to mask hospital staff or investigators. The primary outcome measure was mortality within 90 days of surgery. Analyses were done on an intention-to-treat basis. This study is registered with the ISRCTN registry, number ISRCTN80682973. Findings: Treatment took place between March 3, 2014, and Oct 19, 2015. 22 754 patients were assessed for elegibility. Of 15 873 eligible patients from 93 NHS hospitals, primary outcome data were analysed for 8482 patients in the usual care group and 7374 in the QI group. Eight patients in the usual care group and nine patients in the QI group were not included in the analysis because of missing primary outcome data. The primary outcome of 90-day mortality occurred in 1210 (16%) patients in the QI group compared with 1393 (16%) patients in the usual care group (HR 1·11, 0·96–1·28). Interpretation: No survival benefit was observed from this QI programme to implement a care pathway for patients undergoing emergency abdominal surgery. Future QI programmes should ensure that teams have both the time and resources needed to improve patient care. Funding: National Institute for Health Research Health Services and Delivery Research Programme

Effectiveness of a national quality improvement programme to improve survival after emergency abdominal surgery (EPOCH): a stepped-wedge cluster-randomised trial

BACKGROUND: Emergency abdominal surgery is associated with poor patient outcomes. We studied the effectiveness of a national quality improvement (QI) programme to implement a care pathway to improve survival for these patients. METHODS: We did a stepped-wedge cluster-randomised trial of patients aged 40 years or older undergoing emergency open major abdominal surgery. Eligible UK National Health Service (NHS) hospitals (those that had an emergency general surgical service, a substantial volume of emergency abdominal surgery cases, and contributed data to the National Emergency Laparotomy Audit) were organised into 15 geographical clusters and commenced the QI programme in a random order, based on a computer-generated random sequence, over an 85-week period with one geographical cluster commencing the intervention every 5 weeks from the second to the 16th time period. Patients were masked to the study group, but it was not possible to mask hospital staff or investigators. The primary outcome measure was mortality within 90 days of surgery. Analyses were done on an intention-to-treat basis. This study is registered with the ISRCTN registry, number ISRCTN80682973. FINDINGS: Treatment took place between March 3, 2014, and Oct 19, 2015. 22 754 patients were assessed for elegibility. Of 15 873 eligible patients from 93 NHS hospitals, primary outcome data were analysed for 8482 patients in the usual care group and 7374 in the QI group. Eight patients in the usual care group and nine patients in the QI group were not included in the analysis because of missing primary outcome data. The primary outcome of 90-day mortality occurred in 1210 (16%) patients in the QI group compared with 1393 (16%) patients in the usual care group (HR 1·11, 0·96-1·28). INTERPRETATION: No survival benefit was observed from this QI programme to implement a care pathway for patients undergoing emergency abdominal surgery. Future QI programmes should ensure that teams have both the time and resources needed to improve patient care. FUNDING: National Institute for Health Research Health Services and Delivery Research Programme

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Silent reading and the medieval text: the development of reading practices in the early prints of William Langland and John Lydgate

This thesis is concerned with reading practices and the late medieval vernacular text. More specifically, it is concerned with the ways in which the medieval text was read and received in early modern England. The analysis focuses on two texts in their early modern instantiations: the late fourteenth century allegorical dream vision Piers Plowman by William Langland, and the early fifteenth century Fall of Princes, a translation of Boccaccio’s De Casibus Virorum Illustrium by Benedictine monk John Lydgate. The thesis considers the reception of these poems as they are reworked and reread by successive editors and readers during the shift from script to print, and from a culture of orality to a culture of silent reading. The reception of and editorial policy applied to these texts are considered in relation to the political and religious upheavals of the sixteenth century, and to developments in literacy and literary culture. The editions selected for analysis range from an early manuscript of a B-text version of Piers Plowman, Trinity College Cambridge, MS B.15.17, through to an early seventeenth century print of the Mirror for Magistrates, an early modern reworking of Lydgate’s Fall, published in 1619. The thesis engages with Zumthor’s theory of textual mouvance in that each edition is granted the authority of its own circumstances of production and reception. The synchronic analysis highlights the economic and political pressures which influenced and/or constrained editorial decisions. In charting the various editions through the fifteenth and sixteenth centuries, the thesis provides a complementary diachronic perspective which places each edition within the wider history of textual transmission and in relation to developments in literary culture. The combined synchronic and diachronic analysis of the printed late medieval text provides an insight into developments in reading habits and changing attitudes towards authorship and the functions of literature more generally. The evidence for the development of reading practices can be found in the interaction between the text and its systems of punctuation and paratext. Systems of punctuation and features of paratext act as guide and mediator between the text and the reader; it is these forms and levels of mediation, and the relationship between them, which can indicate patterns of literacy and reader engagement. Thus, developments in the systems of punctuation and paratext interact with changing models of the reader and the various types of ‘literate activities’ available to them (Salter 2012: 67). The late medieval period has been described as a culture of ‘literate orality’ (Sponsler 2010: 1) and its readers exhibited a diverse range of reading practices. The oral and aural characteristics of literary culture gradually declined in the late medieval and early modern periods but a ‘critical mass’ of silent readers did not emerge until the end of the seventeenth century (Jajdelska 2007). Adopting and adapting Jajdelska’s theory of the changing reader model, this thesis focuses on the chosen texts as they appear before the emergence of this ‘critical mass’. The analysis of reading practices, therefore, pertains to the period of transition during which readers negotiated existing oral/aural reading environments while moving towards a predominantly silent reading culture. The thesis demonstrates that the transition was gradual and that sixteenth-century literary culture was diverse in both its reading habits and reading practices. The emerging discipline of historical sociopragmatics provides the theoretical and methodological bridge between the diachronic description of punctuation and paratext, and the examination of reading practices. Historical sociopragmatics allows established insights from sociolinguistics and pragmatics to be applied to the written historical text, creating new opportunities for the recovery and analysis of textual production, editorial treatment and reader engagement. This thesis brings the sociopragmatic concept of ‘situational contexts’ (Culpepper 2011: 4) to the analysis of the physical page and, more specifically, to the interactions between punctuation and paratextual systems. By applying a sociopragmatic approach to the concept of the reader model, this thesis demonstrates that systems of punctuation and paratext provide important evidence for the history textual transmission, reader engagement and the development of reading practices

Prospective observational cohort study on grading the severity of postoperative complications in global surgery research

Background The Clavien–Dindo classification is perhaps the most widely used approach for reporting postoperative complications in clinical trials. This system classifies complication severity by the treatment provided. However, it is unclear whether the Clavien–Dindo system can be used internationally in studies across differing healthcare systems in high- (HICs) and low- and middle-income countries (LMICs). Methods This was a secondary analysis of the International Surgical Outcomes Study (ISOS), a prospective observational cohort study of elective surgery in adults. Data collection occurred over a 7-day period. Severity of complications was graded using Clavien–Dindo and the simpler ISOS grading (mild, moderate or severe, based on guided investigator judgement). Severity grading was compared using the intraclass correlation coefficient (ICC). Data are presented as frequencies and ICC values (with 95 per cent c.i.). The analysis was stratified by income status of the country, comparing HICs with LMICs. Results A total of 44 814 patients were recruited from 474 hospitals in 27 countries (19 HICs and 8 LMICs). Some 7508 patients (16·8 per cent) experienced at least one postoperative complication, equivalent to 11 664 complications in total. Using the ISOS classification, 5504 of 11 664 complications (47·2 per cent) were graded as mild, 4244 (36·4 per cent) as moderate and 1916 (16·4 per cent) as severe. Using Clavien–Dindo, 6781 of 11 664 complications (58·1 per cent) were graded as I or II, 1740 (14·9 per cent) as III, 2408 (20·6 per cent) as IV and 735 (6·3 per cent) as V. Agreement between classification systems was poor overall (ICC 0·41, 95 per cent c.i. 0·20 to 0·55), and in LMICs (ICC 0·23, 0·05 to 0·38) and HICs (ICC 0·46, 0·25 to 0·59). Conclusion Caution is recommended when using a treatment approach to grade complications in global surgery studies, as this may introduce bias unintentionally

Critical care admission following elective surgery was not associated with survival benefit: prospective analysis of data from 27 countries

This was an investigator initiated study funded by Nestle Health Sciences through an unrestricted research grant, and by a National Institute for Health Research (UK) Professorship held by RP. The study was sponsored by Queen Mary University of London

The surgical safety checklist and patient outcomes after surgery: a prospective observational cohort study, systematic review and meta-analysis

© 2017 British Journal of Anaesthesia Background: The surgical safety checklist is widely used to improve the quality of perioperative care. However, clinicians continue to debate the clinical effectiveness of this tool. Methods: Prospective analysis of data from the International Surgical Outcomes Study (ISOS), an international observational study of elective in-patient surgery, accompanied by a systematic review and meta-analysis of published literature. The exposure was surgical safety checklist use. The primary outcome was in-hospital mortality and the secondary outcome was postoperative complications. In the ISOS cohort, a multivariable multi-level generalized linear model was used to test associations. To further contextualise these findings, we included the results from the ISOS cohort in a meta-analysis. Results are reported as odds ratios (OR) with 95% confidence intervals. Results: We included 44 814 patients from 497 hospitals in 27 countries in the ISOS analysis. There were 40 245 (89.8%) patients exposed to the checklist, whilst 7508 (16.8%) sustained ≥1 postoperative complications and 207 (0.5%) died before hospital discharge. Checklist exposure was associated with reduced mortality [odds ratio (OR) 0.49 (0.32–0.77); P\u3c0.01], but no difference in complication rates [OR 1.02 (0.88–1.19); P=0.75]. In a systematic review, we screened 3732 records and identified 11 eligible studies of 453 292 patients including the ISOS cohort. Checklist exposure was associated with both reduced postoperative mortality [OR 0.75 (0.62–0.92); P\u3c0.01; I2=87%] and reduced complication rates [OR 0.73 (0.61–0.88); P\u3c0.01; I2=89%). Conclusions: Patients exposed to a surgical safety checklist experience better postoperative outcomes, but this could simply reflect wider quality of care in hospitals where checklist use is routine