Biting Tongues/ Critical Theory as Creative Tool: Using Bakhtin’s Theory of Double-Voiced Discourse to Edit a Short Novel

Biting Tongues is a short, character-driven novel set in South East England in 2001. Central to its narrative present is the recovery of 27-year old Adam Strange from a 13-year coma and its repercussions on his mother, Peggy, his father, Bill and his sister, Jess. Although his recovery is initially welcomed, old tensions resurface to force a re-evaluation of each of the four central characters’ senses of self and personal relationships, especially as the truth of the coma, and of events surrounding it, begin to emerge. The narrative is interspersed with segments depicting each character’s personal history and the events leading up to and following Adam’s coma. It is a novel of fragile identities and of alienation, not only of each character from another and from contemporary society, but also of inward alienation from perceived morals, values and sense of self. Critical Theory as Creative Tool describes the process of adapting Mikhail Bakhtin’s theories of double-voiced discourse and polyglossia to develop an editorial tool for critiquing an earlier draft of Biting Tongues which has assisted in creating the draft submitted here. It investigates why such an adaptation is relevant to structural problems posed by themes and content in Biting Tongues and evaluates the strengths of its implementation. Primarily using Bakhtin’s essay ‘Discourse in The Novel’ and the chapter ‘Discourse in Dostoevsky’ from Problems of Dostoevsky’s Poetics (1984), this dissertation also uses the work of other Bakhtinian scholars and counterpoints the main argument with a structuralist reading of the theory of free-indirect discourse

Normal faulting sequence in the Pumqu-Xainza Rift constrained by InSAR and teleseismic body-wave seismology

Normal faulting earthquakes play an important role in the deformation of continents, and pose significant seismic hazard, yet important questions remain about their mechanics. We use InSAR and body-wave seismology to compute dislocation models and centroid moment solutions for four normal-faulting earthquakes (Mw 5.7–6.2) that occurred in the Pumqu-Xainza Rift (PXR), southern Tibet, a region where low-angle normal faulting has previously been inferred. We also use the fault locations and slip to investigate the correlation between earthquakes and surface topography, and to calculate stress interactions between the earthquakes. The InSAR and body-wave models give consistent focal mechanisms except for the magnitude of the 1996 event, which may be overestimated due to postseismic deformation in the long-interval interferograms. We calculate the static stress changes due to coseismic slip and find that the 1993 event was too distant to cause triggering of the later events, but that the 1998 event pair occurred in regions of increased Coulomb stress resulting from the 1996 event. All the fault planes found here dip at 40–60°, reinforcing the absence in observations for low-angle normal faulting earthquakes (dip < 30°) whose focal planes can be determined unambiguously. The fault planes of the 1993 and 1996 events are not associated with any obvious surface geomorphology, suggesting that sometimes it is unreliable to resolve the focal plane ambiguity by geomorphology, even for Mw 6.2 events. Furthermore, these events occurred outside the center of the rift, indicating that the active faulting is more distributed and over a length-scale at least 25–50 km east-west in extent, rather than confined to the 20 km width seen in the current mapped faulting and topography. These results suggest that seismic hazard in other extensional zones worldwide might also be more broadly distributed than suggested by geomorphology

Prognostic model to predict postoperative acute kidney injury in patients undergoing major gastrointestinal surgery based on a national prospective observational cohort study.

Background: Acute illness, existing co-morbidities and surgical stress response can all contribute to postoperative acute kidney injury (AKI) in patients undergoing major gastrointestinal surgery. The aim of this study was prospectively to develop a pragmatic prognostic model to stratify patients according to risk of developing AKI after major gastrointestinal surgery. Methods: This prospective multicentre cohort study included consecutive adults undergoing elective or emergency gastrointestinal resection, liver resection or stoma reversal in 2-week blocks over a continuous 3-month period. The primary outcome was the rate of AKI within 7 days of surgery. Bootstrap stability was used to select clinically plausible risk factors into the model. Internal model validation was carried out by bootstrap validation. Results: A total of 4544 patients were included across 173 centres in the UK and Ireland. The overall rate of AKI was 14·2 per cent (646 of 4544) and the 30-day mortality rate was 1·8 per cent (84 of 4544). Stage 1 AKI was significantly associated with 30-day mortality (unadjusted odds ratio 7·61, 95 per cent c.i. 4·49 to 12·90; P < 0·001), with increasing odds of death with each AKI stage. Six variables were selected for inclusion in the prognostic model: age, sex, ASA grade, preoperative estimated glomerular filtration rate, planned open surgery and preoperative use of either an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker. Internal validation demonstrated good model discrimination (c-statistic 0·65). Discussion: Following major gastrointestinal surgery, AKI occurred in one in seven patients. This preoperative prognostic model identified patients at high risk of postoperative AKI. Validation in an independent data set is required to ensure generalizability

Efficacy and safety of baricitinib or ravulizumab in adult patients with severe COVID-19 (TACTIC-R): a randomised, parallel-arm, open-label, phase 4 trial

Background From early in the COVID-19 pandemic, evidence suggested a role for cytokine dysregulation and complement activation in severe disease. In the TACTIC-R trial, we evaluated the efficacy and safety of baricitinib, an inhibitor of Janus kinase 1 (JAK1) and JAK2, and ravulizumab, a monoclonal inhibitor of complement C5 activation, as an adjunct to standard of care for the treatment of adult patients hospitalised with COVID-19. Methods TACTIC-R was a phase 4, randomised, parallel-arm, open-label platform trial that was undertaken in the UK with urgent public health designation to assess the potential of repurposing immunosuppressants for the treatment of severe COVID-19, stratified by a risk score. Adult participants (aged ≥18 years) were enrolled from 22 hospitals across the UK. Patients with a risk score indicating a 40% risk of admission to an intensive care unit or death were randomly assigned 1:1:1 to standard of care alone, standard of care with baricitinib, or standard of care with ravulizumab. The composite primary outcome was the time from randomisation to incidence (up to and including day 14) of the first event of death, invasive mechanical ventilation, extracorporeal membrane oxygenation, cardiovascular organ support, or renal failure. The primary interim analysis was triggered when 125 patient datasets were available up to day 14 in each study group and we included in the analysis all participants who were randomly assigned. The trial was registered on ClinicalTrials.gov (NCT04390464). Findings Between May 8, 2020, and May 7, 2021, 417 participants were recruited and randomly assigned to standard of care alone (145 patients), baricitinib (137 patients), or ravulizumab (135 patients). Only 54 (39%) of 137 patients in the baricitinib group received the maximum 14-day course, whereas 132 (98%) of 135 patients in the ravulizumab group received the intended dose. The trial was stopped after the primary interim analysis on grounds of futility. The estimated hazard ratio (HR) for reaching the composite primary endpoint was 1·11 (95% CI 0·62–1·99) for patients on baricitinib compared with standard of care alone, and 1·53 (0·88–2·67) for ravulizumab compared with standard of care alone. 45 serious adverse events (21 deaths) were reported in the standard-of-care group, 57 (24 deaths) in the baricitinib group, and 60 (18 deaths) in the ravulizumab group. Interpretation Neither baricitinib nor ravulizumab, as administered in this study, was effective in reducing disease severity in patients selected for severe COVID-19. Safety was similar between treatments and standard of care. The short period of dosing with baricitinib might explain the discrepancy between our findings and those of other trials. The therapeutic potential of targeting complement C5 activation product C5a, rather than the cleavage of C5, warrants further evaluation

Filtering of deep sequencing data reveals the existence of abundant Dicer-dependent small RNAs derived from tRNAs

Deep sequencing technologies such as Illumina, SOLiD, and 454 platforms have become very powerful tools in discovering and quantifying small RNAs in diverse organisms. Sequencing small RNA fractions always identifies RNAs derived from abundant RNA species such as rRNAs, tRNAs, snRNA, and snoRNA, and they are widely considered to be random degradation products. We carried out bioinformatic analysis of deep sequenced HeLa RNA and after quality filtering, identified highly abundant small RNA fragments, derived from mature tRNAs that are likely produced by specific processing rather than from random degradation. Moreover, we showed that the processing of small RNAs derived from tRNAGln is dependent on Dicer in vivo and that Dicer cleaves the tRNA in vitro