Selves and Spaces in Science Fiction

This thesis proposes a critical framework by which science fiction can be read as an indicator of significant trends and debates in science and culture. It takes as its starting point Brian Aldiss's statement that science fiction's purpose is to articulate in fictional form a definition of humanity and its status in the universe that will stand in the light of science. Science fiction exists as a means by which scientific concepts are constructed as cultural interpretations, and as both have changed significantly over the period from the emergence of the genre in the mid nineteenth century through the twentieth century, analysis of science-fictional forms and practices can reveal the processes of their evolution. A critical framework is constructed based on Aldiss' definition, identifying first, a construction of selfhood and spatiality - physical and metaphysical - as being fundamental, and secondly, identifying the emergence and evolution of major 'Orders' that take different approaches to key issues and which engage with each other both antagonistically and creatively. The thesis begins with an investigation of the cultural construction of space and then covers the emergence of science fiction as it relates to the project to define humanity and its standing in the universe in a manner consistent with science. Three Orders and their emergence are then described according to their architectonic schemae and their epistemological and creative processes. The first is the Modernist Order, based on Cartesian spatiality and mind-body dualism and empirical scientific practice. The second, which emerged as an attempt to synthesise modern science with traditional culture, is the Neohumanist Order. The third, still very much in flux, is the Posthumanist Order, which is very much inspired both by postmodernism and cybernetics. The three following chapters deal with the Orders in turn, selecting exemplary texts from their emergent and developed (or developing) stages, suggesting also the points in the development of each where another Order has disengaged and emerged in its own right. Because science and culture evolve over time, examination of the Orders is intrinsically linked to a concept of science fiction as being an ongoing discourse, each selected text is interpreted as being a response to a particular issue at a particular cultural moment, but nonetheless connected to predecessor and successor texts that represent a line of argument pursued over time within and between Orders. The Orders are not hermetic by any means, and their most enlightening aspects can be their varying treatment of a common concept. The cyborg furnishes an excellent example, being treated differently by each of the Orders as it is an image of the integration of humanity and technology. Issues such as self, body, boundary, location, the other and communication are all represented in the cyborg and the next two chapters discuss the cyborg as treated by different Orders, in the first case, as a body and in the second case, as an inhabitant and creation of architectonics and culture. The conclusion then discusses the current state of affairs regarding the system of Orders as a critical method. It is shown that 'impure' texts that contain aspects of each of the Orders do not negate their usefulness, but rather demonstrate it as texts (and postmodern texts in particular) provide stages on which the Orders can be displayed engaging with each other

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

Selves and Spaces in Science Fiction

This thesis proposes a critical framework by which science fiction can be read as an indicator of significant trends and debates in science and culture. It takes as its starting point Brian Aldiss's statement that science fiction's purpose is to articulate in fictional form a definition of humanity and its status in the universe that will stand in the light of science. Science fiction exists as a means by which scientific concepts are constructed as cultural interpretations, and as both have changed significantly over the period from the emergence of the genre in the mid nineteenth century through the twentieth century, analysis of science-fictional forms and practices can reveal the processes of their evolution. A critical framework is constructed based on Aldiss' definition, identifying first, a construction of selfhood and spatiality - physical and metaphysical - as being fundamental, and secondly, identifying the emergence and evolution of major 'Orders' that take different approaches to key issues and which engage with each other both antagonistically and creatively. The thesis begins with an investigation of the cultural construction of space and then covers the emergence of science fiction as it relates to the project to define humanity and its standing in the universe in a manner consistent with science. Three Orders and their emergence are then described according to their architectonic schemae and their epistemological and creative processes. The first is the Modernist Order, based on Cartesian spatiality and mind-body dualism and empirical scientific practice. The second, which emerged as an attempt to synthesise modern science with traditional culture, is the Neohumanist Order. The third, still very much in flux, is the Posthumanist Order, which is very much inspired both by postmodernism and cybernetics. The three following chapters deal with the Orders in turn, selecting exemplary texts from their emergent and developed (or developing) stages, suggesting also the points in the development of each where another Order has disengaged and emerged in its own right. Because science and culture evolve over time, examination of the Orders is intrinsically linked to a concept of science fiction as being an ongoing discourse, each selected text is interpreted as being a response to a particular issue at a particular cultural moment, but nonetheless connected to predecessor and successor texts that represent a line of argument pursued over time within and between Orders. The Orders are not hermetic by any means, and their most enlightening aspects can be their varying treatment of a common concept. The cyborg furnishes an excellent example, being treated differently by each of the Orders as it is an image of the integration of humanity and technology. Issues such as self, body, boundary, location, the other and communication are all represented in the cyborg and the next two chapters discuss the cyborg as treated by different Orders, in the first case, as a body and in the second case, as an inhabitant and creation of architectonics and culture. The conclusion then discusses the current state of affairs regarding the system of Orders as a critical method. It is shown that 'impure' texts that contain aspects of each of the Orders do not negate their usefulness, but rather demonstrate it as texts (and postmodern texts in particular) provide stages on which the Orders can be displayed engaging with each other

Effect of lower tidal volume ventilation facilitated by extracorporeal carbon dioxide removal vs standard care ventilation on 90-day mortality in patients with acute hypoxemic respiratory failure

Importance In patients who require mechanical ventilation for acute hypoxemic respiratory failure, further reduction in tidal volumes, compared with conventional low tidal volume ventilation, may improve outcomes. Objective To determine whether lower tidal volume mechanical ventilation using extracorporeal carbon dioxide removal improves outcomes in patients with acute hypoxemic respiratory failure. Design, Setting, and Participants This multicenter, randomized, allocation-concealed, open-label, pragmatic clinical trial enrolled 412 adult patients receiving mechanical ventilation for acute hypoxemic respiratory failure, of a planned sample size of 1120, between May 2016 and December 2019 from 51 intensive care units in the UK. Follow-up ended on March 11, 2020. Interventions Participants were randomized to receive lower tidal volume ventilation facilitated by extracorporeal carbon dioxide removal for at least 48 hours (n = 202) or standard care with conventional low tidal volume ventilation (n = 210). Main Outcomes and Measures The primary outcome was all-cause mortality 90 days after randomization. Prespecified secondary outcomes included ventilator-free days at day 28 and adverse event rates. Results Among 412 patients who were randomized (mean age, 59 years; 143 [35%] women), 405 (98%) completed the trial. The trial was stopped early because of futility and feasibility following recommendations from the data monitoring and ethics committee. The 90-day mortality rate was 41.5% in the lower tidal volume ventilation with extracorporeal carbon dioxide removal group vs 39.5% in the standard care group (risk ratio, 1.05 [95% CI, 0.83-1.33]; difference, 2.0% [95% CI, −7.6% to 11.5%]; P = .68). There were significantly fewer mean ventilator-free days in the extracorporeal carbon dioxide removal group compared with the standard care group (7.1 [95% CI, 5.9-8.3] vs 9.2 [95% CI, 7.9-10.4] days; mean difference, −2.1 [95% CI, −3.8 to −0.3]; P = .02). Serious adverse events were reported for 62 patients (31%) in the extracorporeal carbon dioxide removal group and 18 (9%) in the standard care group, including intracranial hemorrhage in 9 patients (4.5%) vs 0 (0%) and bleeding at other sites in 6 (3.0%) vs 1 (0.5%) in the extracorporeal carbon dioxide removal group vs the control group. Overall, 21 patients experienced 22 serious adverse events related to the study device. Conclusions and Relevance Among patients with acute hypoxemic respiratory failure, the use of extracorporeal carbon dioxide removal to facilitate lower tidal volume mechanical ventilation, compared with conventional low tidal volume mechanical ventilation, did not significantly reduce 90-day mortality. However, due to early termination, the study may have been underpowered to detect a clinically important difference