Philosophy and Aesthetics Inform Science: illuminating the complex dynamics of seeing

Aesthetic responsivity and the phenomenology of arts processes reflect integrative self-world engagements, and are informative about the nature of the world and our biology in ways that are often not be made evident through scientific research. Akins’ and Hahn’s research regarding human trichromatic visual perception brings together the art of photography, neuroscience, and psychophysics, along with analyses of perspectives on vision in science and philosophy, to invoke anti-reductive, holistic understandings of how we see colour. We bring aesthetics and the phenomenology of arts processes to bear in exploring creaturely re-sponsivity to the complex inter-relational dynamics of light perception, and o˙er reflective metaphors for human engagements that challenge Darwinian utilitarian conceptions. We argue that attending to aesthetic and phenomenological aspects of experiences is essential to understanding how the shared circuits of cognition and sensory-motor engagement shape our perceptive responsive interactions

Ethics as Harmony and Improvisation in Responsive Equilibrium: the Core Psychophysical Process as a bio-logical foundation for ethical engagement

In this thesis I address the ethics of corporeal being at a foundational level. Rather than starting the discussion of ethics at an abstract level founded in propositions and logical arguments about principles, I offer an holistic view of human engagement that recognises sensori-motor processes and our embodied engagements with the world as foundational to and integral with cognition and higher functions and social skills. I propose that the capacity of human beings to act in an ethically responsible way is built into our biological, psychosocial natures, and that ethical interaction is informed and enhanced by intentionally cultivating a particular psychophysical process. The Core Psychophysical Process (the CPP) that I have identified naturally underlies our interactions in the world as vertebrate creatures, grounds our primary and ongoing developmental and learning processes, and is integral with the process of developing our ethical ‘second nature.’ The CPP is expressed at a fundamental level in a reflexive neuro-musculo-skeletal expansive and contractive process that is integral with an experiential sequence of perception, reaction, and reflection leading to choice of action. There is a constant ebb and flow of contraction and expansion throughout the body which resonates with, in and through all of our experiences. It is integrated into processes of reasoning, interpretation, intentionality, emotion, valuing and habit, all of which, along with the abilities to inhibit, deliberate, and choose, are foundational to ethical action. Elements of the CPP are active at every level of corporeal being, from the fluent maintenance of equilibrium at neuronal level through to the dynamics of ethical deliberations and negotiations between people in society. In this thesis the Alexander Technique and processes in the Arts provide exemplars wherein the foundational intrinsic aspects and expressions of the CPP can be understood. In order to fully explore the impact of the CPP in human experience, I examine both theoretical and practical experimental experience with the CPP in relation to: historical and contemporary readings from different cultures in bioethics, ethics, philosophy, feminist philosophy, and the philosophy of mind; empirical investigations in cognitive science, physiology, and neuroscience; and Susan Hurley’s Shared Circuits Model. This is a phenomenological study, from a feminist and arts-based perspective. Arts Phenomenology starts with the question: ‘What is the experience of being with, acting with, with the intention to?’ That perspective leaves behind subject/object, mind/body dualities to understand human experience as extended and grounded in the embodied interactions of social being. I offer alternate conceptions of embodiment, and explore Bodily ‘I’dentity that reflects multi-sensory meaning-making grounded in experience

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

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

Ethics as Harmony and Improvisation in Responsive Equilibrium: the Core Psychophysical Process as a bio-logical foundation for ethical engagement

In this thesis I address the ethics of corporeal being at a foundational level. Rather than starting the discussion of ethics at an abstract level founded in propositions and logical arguments about principles, I offer an holistic view of human engagement that recognises sensori-motor processes and our embodied engagements with the world as foundational to and integral with cognition and higher functions and social skills. I propose that the capacity of human beings to act in an ethically responsible way is built into our biological, psychosocial natures, and that ethical interaction is informed and enhanced by intentionally cultivating a particular psychophysical process. The Core Psychophysical Process (the CPP) that I have identified naturally underlies our interactions in the world as vertebrate creatures, grounds our primary and ongoing developmental and learning processes, and is integral with the process of developing our ethical ‘second nature.’ The CPP is expressed at a fundamental level in a reflexive neuro-musculo-skeletal expansive and contractive process that is integral with an experiential sequence of perception, reaction, and reflection leading to choice of action. There is a constant ebb and flow of contraction and expansion throughout the body which resonates with, in and through all of our experiences. It is integrated into processes of reasoning, interpretation, intentionality, emotion, valuing and habit, all of which, along with the abilities to inhibit, deliberate, and choose, are foundational to ethical action. Elements of the CPP are active at every level of corporeal being, from the fluent maintenance of equilibrium at neuronal level through to the dynamics of ethical deliberations and negotiations between people in society. In this thesis the Alexander Technique and processes in the Arts provide exemplars wherein the foundational intrinsic aspects and expressions of the CPP can be understood. In order to fully explore the impact of the CPP in human experience, I examine both theoretical and practical experimental experience with the CPP in relation to: historical and contemporary readings from different cultures in bioethics, ethics, philosophy, feminist philosophy, and the philosophy of mind; empirical investigations in cognitive science, physiology, and neuroscience; and Susan Hurley’s Shared Circuits Model. This is a phenomenological study, from a feminist and arts-based perspective. Arts Phenomenology starts with the question: ‘What is the experience of being with, acting with, with the intention to?’ That perspective leaves behind subject/object, mind/body dualities to understand human experience as extended and grounded in the embodied interactions of social being. I offer alternate conceptions of embodiment, and explore Bodily ‘I’dentity that reflects multi-sensory meaning-making grounded in experience

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

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

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