“O, she’s warm!”: The taking of hands … and bears … and time’s … in The Winter’s Tale

Shakespeare wrote words and plays. Words might well be considered to be the ‘life blood’ of a play. But plays are more than words. Plays have characters, movement, costumes and props. Words inhabit and animate, give rhyme and reason to an actor being on a stage, performing for an audience. But between the words, the play still exists. This thesis is an exploration of those ‘moments’ that are played out in silence and are watched rather than heard. To tell the story of The Winter’s Tale, Shakespeare was faced with some specific problems. There are essentially two tales to be told in the space of one play. The first requires for an all consuming jealousy to be played out. He solved this with a simple and understandable wordless action. Then to conclude this first tragic section, the story demanded that a helpless baby be abandoned - lost. Here he used an old trick in a new and surprising way, to be played quickly and, with his unerring sense of staging, for a laugh. The second tale then had to begin, and the baby had to become a woman. For this he used a convention - unconventionally. Finally, at the end of the play, he decided to change the story. To conclude his tale, the tale he was telling, with an image of redemption, reconciliation and hope. Of all the moments, this is the one that is the quietest, slowest and most beautifully painted. This thesis is an exploration of those moments. A discussion about how Shakespeare, who has probably added more words into the lexicon that any other person, was also essentially a visual artist. That he ‘drew and painted and sculpted’ - creating stage pictures

B 12 -Mediated, Long Wavelength Photopolymerization of Hydrogels

Medical hydrogel applications have expanded rapidly over the past decade. Implantation in patients by non-invasive injection is preferred, but this requires hydrogel solidification from a low viscosity solution to occur in vivo via an applied stimuli. Transdermal photo-crosslinking of acrylated biopolymers with photoinitiators and lights offers a mild, spatiotemporally controlled solidification trigger. However, the current short wavelength initiators limit curing depth and efficacy because they do not absorb within the optical window of tissue (600 - 900 nm). As a solution to the current wavelength limitations, we report the development of a red light responsive initiator capable of polymerizing a range of acrylated monomers. Photo-activation occurs within a range of skin type models containing high biochromophore concentrations

Traumatic events, other operational stressors and physical and mental health reported by Australian Defence Force personnel following peacekeeping and war-like deployments

Background: The association between stressful events on warlike deployments and subsequent mental health problems has been established. Less is known about the effects of stressful events on peacekeeping deployments. Methods: Two cross sectional studies of the Australian Defence Force were used to contrast the prevalence of exposures reported by a group deployed on a peacekeeping operation (Bougainville, n=1704) and those reported by a group deployed on operations which included warlike and non-warlike exposures (East Timor, n=1333). A principal components analysis was used to identify groupings of non-traumatic exposures on deployment. Multiple regression models were used to assess the association between self-reported objective and subjective exposures, stressors on deployment and subsequent physical and mental health outcomes. Results: The principal components analysis produced four groups of non-traumatic stressors which were consistent between the peacekeeping and more warlike deployments. These were labelled ‘separation’, ‘different culture’, ‘other people’ and ‘work frustration’. Higher levels of traumatic and non-traumatic exposures were reported by veterans of East Timor compared to Bougainville. Higher levels of subjective traumatic exposures were associated with increased rates of PTSD in East Timor veterans and more physical and psychological health symptoms in both deployed groups. In Bougainville and East Timor veterans some non-traumatic deployment stressors were also associated with worse health outcomes. Conclusion: Strategies to best prepare, identify and treat those exposed to traumatic events and other stressors on deployment should be considered for Defence personnel deployed on both warlike and peacekeeping operations.Michael Waller, Susan A Treloar, Malcolm R Sim, Alexander C McFarlane, Annabel C L McGuire, Jonathan Bleier and Annette J Dobso

Effect of Hydrocortisone on Mortality and Organ Support in Patients With Severe COVID-19: The REMAP-CAP COVID-19 Corticosteroid Domain Randomized Clinical Trial.

Importance: Evidence regarding corticosteroid use for severe coronavirus disease 2019 (COVID-19) is limited. Objective: To determine whether hydrocortisone improves outcome for patients with severe COVID-19. Design, Setting, and Participants: An ongoing adaptive platform trial testing multiple interventions within multiple therapeutic domains, for example, antiviral agents, corticosteroids, or immunoglobulin. Between March 9 and June 17, 2020, 614 adult patients with suspected or confirmed COVID-19 were enrolled and randomized within at least 1 domain following admission to an intensive care unit (ICU) for respiratory or cardiovascular organ support at 121 sites in 8 countries. Of these, 403 were randomized to open-label interventions within the corticosteroid domain. The domain was halted after results from another trial were released. Follow-up ended August 12, 2020. Interventions: The corticosteroid domain randomized participants to a fixed 7-day course of intravenous hydrocortisone (50 mg or 100 mg every 6 hours) (n = 143), a shock-dependent course (50 mg every 6 hours when shock was clinically evident) (n = 152), or no hydrocortisone (n = 108). Main Outcomes and Measures: The primary end point was organ support-free days (days alive and free of ICU-based respiratory or cardiovascular support) within 21 days, where patients who died were assigned -1 day. The primary analysis was a bayesian cumulative logistic model that included all patients enrolled with severe COVID-19, adjusting for age, sex, site, region, time, assignment to interventions within other domains, and domain and intervention eligibility. Superiority was defined as the posterior probability of an odds ratio greater than 1 (threshold for trial conclusion of superiority >99%). Results: After excluding 19 participants who withdrew consent, there were 384 patients (mean age, 60 years; 29% female) randomized to the fixed-dose (n = 137), shock-dependent (n = 146), and no (n = 101) hydrocortisone groups; 379 (99%) completed the study and were included in the analysis. The mean age for the 3 groups ranged between 59.5 and 60.4 years; most patients were male (range, 70.6%-71.5%); mean body mass index ranged between 29.7 and 30.9; and patients receiving mechanical ventilation ranged between 50.0% and 63.5%. For the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively, the median organ support-free days were 0 (IQR, -1 to 15), 0 (IQR, -1 to 13), and 0 (-1 to 11) days (composed of 30%, 26%, and 33% mortality rates and 11.5, 9.5, and 6 median organ support-free days among survivors). The median adjusted odds ratio and bayesian probability of superiority were 1.43 (95% credible interval, 0.91-2.27) and 93% for fixed-dose hydrocortisone, respectively, and were 1.22 (95% credible interval, 0.76-1.94) and 80% for shock-dependent hydrocortisone compared with no hydrocortisone. Serious adverse events were reported in 4 (3%), 5 (3%), and 1 (1%) patients in the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively. Conclusions and Relevance: Among patients with severe COVID-19, treatment with a 7-day fixed-dose course of hydrocortisone or shock-dependent dosing of hydrocortisone, compared with no hydrocortisone, resulted in 93% and 80% probabilities of superiority with regard to the odds of improvement in organ support-free days within 21 days. However, the trial was stopped early and no treatment strategy met prespecified criteria for statistical superiority, precluding definitive conclusions. Trial Registration: ClinicalTrials.gov Identifier: NCT02735707

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

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

An application of Gascoigne’s Certayne notes of instruction to a bouquet of his Posies

The critical literature on George Gascoigne suffers from a serious omission: there has been no attempt to apply Gascoigne's Certayne Notes of Instruction concerning the making of verse or ryme in English, written at the request of Master Edouardo Donati¹ to any extended portion of his poetry, in a thorough way, toward an interpretative end. That a poet's poetics would not be so applied to his poetry is certainly ironic. The irony is intensified in this instance, because in all probability Gascoigne wrote the Notes after most of the poetry was composed.² In consequence, there is a considerable likelihood that the Notes might have been in part formulated through a process of inductive reasoning from patterns found in the poetry, not simply through logical deduction. Therefore, they are naturally applicable to the body of poetry which they follow (The Posies of George Gascoigne Esquire: Corrected, perfected, and augmented by the Author).³ My study is directed toward rectifying this omission in the critical literature on Gascoigne. In the first chapter, I examine the published critiques of Gascoigne which bear upon the relation between Gascoigne's poetic theory and his poetic practice. As I hope to show in that chapter that there has indeed been a failure to examine thoroughly any body of Gascoigne's work in terms of his own stated poetic principles, I should note here that, accordingly, I shall not incorporate critical references in the concluding chapter devoted to my reading of the poems (for there are no. critical references to the poems considered herein that are the products of any method of interpretation that is at all similar to my own). Occasional similarities in the literature on Gascoigne, either of observation or of interpretation with respect to particular poems, are at most representative of parallel methodologies or conclusions. They may sometimes be similar to, but they lie in distinctly different currents from, the new interpretative channel that I hope to establish. In Chapter II, I anatomize the poetic principles enunciated by Gascoigne in his Notes. I also attempt in this chapter to place Gascoigne's theories in the historical mainstream of ideas similar to his own. In the last chapter, which justifies the first two, I apply Gascoigne's principles to a coherent body of his poetry. Since I cannot treat all of Gascoigne's poems within the limits of a thesis, I restrict my selection to the "Flowers" division of the Posies. It makes sense to deal with those which are found in the first set of his poems (as established in the edition that he "Corrected, perfected, and augmented"). As suggested by the titles of these sets, "Flowers" exemplify more fully the application of his beliefs than would poems included as "Herbes," and exemplify that application better than would those classified as "Weedes." The principles that guide my selectivity within this framework will be explained at the beginning of the chapter in which the poems are analyzed. This chapter will conclude my thesis. As interpretative conclusions cannot be generalized, as the critical generalizations that can be made will be made in it, as the test of interpretative application of the Notes is the conclusion of all that precedes it, and as the reader must be the final judge of the method and interpretations contained in it, I shall not follow this chapter with another which, given the nature of this thesis, would be either unwarranted or redundant. I conclude this study, therefore, with this chapter.Arts, Faculty ofEnglish, Department ofGraduat

The nature of microphase separation in perfluorinated ionomers

Bibliography: p. 147-158.The microstructural environment of the perfluorinated ionomers produced by Dow and Dupont have been investigated by the use of fluorescent probe techniques. The polarity of the interfacial region in these polymers was found to be more polar for the sulphonate than the carboxylate form, and with increasing ion content. The locations of cesium ion, iodide ion and copper (II) ion were all found to be different, and to change with ion content and the identity of exchange group. This is quantitatively explained in terms of a three phase model which is consistent with previous spectroscopic studies of perfluorinated ionomers. Pretreatment was found to have an effect on the microstructural and bulk properties of these polymers. The polarity of the interfacial region studied using fluorescent probes was found to change after swelling in ethanol and boiling in water. The interface appears to become more polar after swelling in ethanol and less polar after boiling in water. The sorbed water in the polymers was studied using near infrared spectroscopy. Its character was also found to change with pretreatment. The most significant effect of ethanol swelling was a subsequent increase in the relative amount of non-hydrogen bonded OH groups. For the boiling pretreatment, the main effect was to increase the average hydrogen bond strength of sorbed water. This is explained in terms of a structural rearrangement with ethanol swelling and an expansion in cluster size with boiling. The insulator-to-conductor percolative threshold for these polymers was found to occur at lower water contents than predicted for randomly distributed conducting sites. This is explained in terms of the connectivity among the clustering entities in the polymers. The threshold moves to even lower water contents for both ethanol and boiling pretreatments. This is again explained in terms of morphological rearrangements in the polymer structure

The long-term mental health impact of peacekeeping:Prevalence and predictors of psychiatric disorder

BACKGROUND: The mental health outcomes of military personnel deployed on peacekeeping missions have been relatively neglected in the military mental health literature. AIMS: To assess the mental health impacts of peacekeeping deployments. METHOD: In total, 1025 Australian peacekeepers were assessed for current and lifetime psychiatric diagnoses, service history and exposure to potentially traumatic events (PTEs). A matched Australian community sample was used as a comparator. Univariate and regression analyses were conducted to explore predictors of psychiatric diagnosis. RESULTS: Peacekeepers had significantly higher 12-month prevalence of post-traumatic stress disorder (16.8%), major depressive episode (7%), generalised anxiety disorder (4.7%), alcohol misuse (12%), alcohol dependence (11.3%) and suicidal ideation (10.7%) when compared with the civilian comparator. The presence of these psychiatric disorders was most strongly and consistently associated with exposure to PTEs. CONCLUSIONS: Veteran peacekeepers had significant levels of psychiatric morbidity. Their needs, alongside those of combat veterans, should be recognised within military mental health initiatives. DECLARATION OF INTEREST: None. COPYRIGHT AND USAGE: This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY) licence