Identifying Priorities in Intensive Care : a description of a system for collecting intensive care data, an analysis of the data collected, a critique of aspects of severity scoring systems used to compare intensive care outcome, identification of priorities in intensive care and proposals to improve outcome for intensive care patients.

MDThis thesis reviews the requirements for intensive care audit data and describes the development of ICARUS (Intensive Care Audit and Resource Utilisation System), a system to collect and analyse intensive care audit information. By the end of 1998 ICARUS contained information on over 45,000 intensive care admissions. A study was performed to determine the accuracy of the data collection and entry in ICARUS. The data in ICARUS was used to investigate some limitations of the APACHE II severity scoring system. The studies examined the effect of changes in physiological values and post-intensive care deaths, and the effect of casemix adjustment on mortality predicted by APACHE II. A hypothesis is presented that excess intensive care mortality in the United Kingdom may be concealed by intensive care mortality prediction models. A critical analysis of ICARUS data was undertaken to identify patient groups most likely to benefit from intensive care. This analysis revealed a high mortality in critically ill patients admitted from the wards to the intensive care unit. To help identify critically ill ward patients, the physiological values and procedures in the 24 hours before intensive care admission from the ward were recorded: examination of the results suggested that management of these patients could be improved. This led to the setting up of a patient at risk team (PART). Two studies report the effect of the PART on patients on the wards and on the patients admitted from the wards to the intensive care unit. Additional care for surgical patients on the wards is suggested as a way of improving the management of high-risk postoperative patients. The thesis concludes by discussing the benefits of the ICARUS system and speculating on the direction that should be taken for intensive care audit in the future

Travelling Companions

Catalogue to accompany exhibition 'Travelling Companions' at Art at the Alison Richard Building, University of Cambridge. Curator Ro Spankie, Artists Fay Ballard + Judy Goldhil

The Limits of the Case Study: Exemplarity and the Reception of Classical Literature

This article considers the role of the case study as a form, with special reference to classical reception studies. It considers the history and theory of exemplification within rhetoric and within literary criticism (and other forms of writing), with due attention to the special place that classicism makes for the exemplary nature of the antiquity of Greece and Rome—and thus the special place of such exemplification in the reception of antiquity by modern writers and thinkers. It concludes first that the exemplification of the case-study constructs specific models of temporality that construct the self as a historically located subject: thus we should be particularly aware of the politics of the case study, the dynamic of responsibility and response in taking the past as a model for the present. Second, it concludes that to construct a case study is to commit to a model of social epistemology—about what knowing the past is, how tradition and repetition are to be constructed. Thus, thirdly, a reader’s desire is always a constitutive but disruptive factor in the construction of the case study

A Mother's Joy at Her Child's Death: Conversion, Cognitive Dissonance, and Grief

This article explores how a sophisticated woman, Minnie Benson, could have rejoiced when her beloved son died at school at age 18. Her joyous reaction—remarked on by all her family—is in stark contrast to that of her husband, Bishop Edward White Benson, who was devastated by the death and found it the most dismaying challenge to his deeply-felt faith. Her reaction is investigated in particular through her personal Evangelical conversion and her commitment to believing literally in joy at suffering. This literalism is set in contrast to standard normative Christian responses to a child's death. The article discusses the cognitive dissonance of religious responses to death in the Victorian era, and how converts are socialized into expected horizons of response.ER

Multisite analysis of the timing and outcomes of unplanned transfers from subacute to acute care.

OBJECTIVE: The aim of the present study was to examine the timing and outcomes of patients requiring an unplanned transfer from subacute to acute care. METHODS: Subacute care in-patients requiring unplanned transfer to an acute care facility within four Victorian health services from 1 January to 31 December 2010 were included in the study. Data were collected using retrospective audit. The primary outcome was transfer within 24 h of subacute care admission. RESULTS: In all, 431 patients (median age 81 years) had unplanned transfers; of these, 37.8% had a limitation of medical treatment (LOMT) order. The median subacute care length of stay was 43 h: 29.0% of patients were transferred within 24 h and 83.5% were transferred within 72 h of subacute care admission. Predictors of transfer within 24 h were comorbidity weighting (odds ratio (OR) 1.1, P = 0.02) and LOMT order (OR 2.1, P < 0.01). Hospital admission occurred in 87.2% of patients and 15.4% died in hospital. Predictors of in-hospital mortality were comorbidity weighting (OR 1.2, P < 0.01) and the number of physiological abnormalities in the 24 h preceding transfer (OR 1.3, P < 0.01). CONCLUSIONS: There is a high rate of unplanned transfers to acute care within 24h of admission to subacute care. Unplanned transfers are associated with high hospital admission and in-hospital mortality rates

Accuracy of an expanded early warning score for patients in general and trauma surgery wards

Background: Early warning scores (EWS) may aid the prediction of major adverse events in hospitalized patients. Recently, an expanded EWS was introduced in the Netherlands. The aim of this study was to assess the relationship between this EWS and the occurrence of major adverse clinical events during hospitalization of patients admitted to a general and trauma surgery ward. Methods: This was a prospective cohort study of consecutive patients admitted to the general and trauma surgery ward of a university medical centre (March-September 2009). Follow-up was limited to the time the patient was hospitalized. Logistic regression analysis was used to assess the relationship between the EWS and the occurrence of the composite endpoint consisting of death, reanimation, unexpected intensive care unit admission, emergency surgery and severe complications. Performance of the EWS was analysed using sensitivity, specificity, predictive values and receiver operating characteristic (ROC) curves. Results: A total of 572 patients were included. During a median follow-up of 4 days, 46 patients (8.0 per cent) reached the composite endpoint (two deaths, two reanimations, 17 intensive care unit admissions, 44 severe complications, one emergency operation). An EWS of at least 3, adjusted for baseline American Society of Anesthesiology classification, was associated with a significantly higher risk of reaching the composite endpoint (odds ratio 11·3, 95 per cent confidence interval (c.i.) 5·5 to 22·9). The area under the ROC curve was 0·87 (95 per cent c.i. 0·81 to 0·93). When considering an EWS of at least 3 to be a positive test result, sensitivity was 74 per cent and specificity was 82 per cent. Conclusion: An EWS of 3 or more is an independent predictor of major adverse events in patients admitted to a general and trauma surgery ward

Mammalian ANP32A and ANP32B proteins drive differential polymerase adaptations in avian influenza virus

ANP32 proteins, which act as influenza polymerase cofactors, vary between birds and mammals. In mammals, ANP32A and ANP32B have been reported to serve essential but redundant roles to support influenza polymerase activity. The well-known mammalian adaptation PB2-E627K enables influenza polymerase to use mammalian ANP32 proteins. However, some mammalian-adapted influenza viruses do not harbor this substitution. Here, we show that alternative PB2 adaptations, Q591R and D701N, also allow influenza polymerase to use mammalian ANP32 proteins, whereas other PB2 mutations, G158E, T271A, and D740N, increase polymerase activity in the presence of avian ANP32 proteins as well. Furthermore, PB2-E627K strongly favors use of mammalian ANP32B proteins, whereas D701N shows no such bias. Accordingly, PB2-E627K adaptation emerges in species with strong pro-viral ANP32B proteins, such as humans and mice, while D701N is more commonly seen in isolates from swine, dogs, and horses, where ANP32A proteins are the preferred cofactor. Using an experimental evolution approach, we show that the passage of viruses containing avian polymerases in human cells drove acquisition of PB2-E627K, but not in the absence of ANP32B. Finally, we show that the strong pro-viral support of ANP32B for PB2-E627K maps to the low-complexity acidic region (LCAR) tail of ANP32B. IMPORTANCE Influenza viruses naturally reside in wild aquatic birds. However, the high mutation rate of influenza viruses allows them to rapidly and frequently adapt to new hosts, including mammals. Viruses that succeed in these zoonotic jumps pose a pandemic threat whereby the virus adapts sufficiently to efficiently transmit human-to-human. The influenza virus polymerase is central to viral replication and restriction of polymerase activity is a major barrier to species jumps. ANP32 proteins are essential for influenza polymerase activity. In this study, we describe how avian influenza viruses can adapt in several different ways to use mammalian ANP32 proteins. We further show that differences between mammalian ANP32 proteins can select different adaptive changes and are responsible for some of the typical mutations that arise in mammalian-adapted influenza polymerases. These different adaptive mutations may determine the relative zoonotic potential of influenza viruses and thus help assess their pandemic risk

The mechanism of resistance to favipiravir in influenza.

Favipiravir is a broad-spectrum antiviral that has shown promise in treatment of influenza virus infections. While emergence of resistance has been observed for many antiinfluenza drugs, to date, clinical trials and laboratory studies of favipiravir have not yielded resistant viruses. Here we show evolution of resistance to favipiravir in the pandemic H1N1 influenza A virus in a laboratory setting. We found that two mutations were required for robust resistance to favipiravir. We demonstrate that a K229R mutation in motif F of the PB1 subunit of the influenza virus RNA-dependent RNA polymerase (RdRP) confers resistance to favipiravir in vitro and in cell culture. This mutation has a cost to viral fitness, but fitness can be restored by a P653L mutation in the PA subunit of the polymerase. K229R also conferred favipiravir resistance to RNA polymerases of other influenza A virus strains, and its location within a highly conserved structural feature of the RdRP suggests that other RNA viruses might also acquire resistance through mutations in motif F. The mutations identified here could be used to screen influenza virus-infected patients treated with favipiravir for the emergence of resistance