Explaining cooperative groups via social niche construction

Cooperative behaviours can be defined as those that benefit others at an apparent cost to self. How these kinds of behaviours evolve has been a topic of great interest in evolutionary biology, as the Darwinian paradigm seems to suggest that nature will be “red in tooth and claw” and that we would not expect one organism to evolve to help another. The evolution-of-cooperation literature has therefore generally been about showing how the altruism involved in these cases is only apparent (see Bergstrom 2002 for an excellent review). Consider kin selection, in which interactions are more likely to occur between related individuals. The cost of altruism to the individual is real but, having identified the correct score-keeping level as the genetic one, it turns out that the cooperative act is not costly but profitable. More generally, successful explanations for cooperation rely on the presence of a population structure that clusters cooperators together, such that they enjoy the benefits of each others' actions. However, the question that has been left largely unaddressed is how does this structure itself evolve? If we want to really explain why organisms cooperate, then we need to explain not just their adaptation to their social environment, but how they came to live in that environment. Recent work by Powers (2010) and Powers et al. (in press) has addressed this question. They show that social behaviour can exert indirect selection pressure on population structure-modifying traits, causing individuals to adaptively modify their population structure to support greater cooperation. Moreover, they argue that any component of selection on structure-modifying traits that is due to social behaviour must be in the direction of increased cooperation; that component of selection cannot be in favour of the conditions for greater selfishness. Powers et al. then examine the conditions under which this component of selection on population structure exists. They argue that not only can population structure drive the evolution of cooperation, as in classical models, but that the benefits of greater cooperation can in turn drive the evolution of population structure: a positive feedback process that they refer to as social niche construction (after Odling-Smee et al. 2003). Maynard Smith and Szathmary (1995) note that most of the big unanswered questions in biology are not about how a particular behaviour is selected for at one level of organization but about the emergence of whole new levels of organization, e.g., the transition from single- to multi-celled organisms, or from solitary insects to eusocial colonies. Any satisfactory account of these transitions must explain how the individuals came to live in a population structure that supported high degrees of cooperation, as well as showing that cooperation is individually advantageous given that structure. The social niche construction process identified by Powers et al. can explain some of the major transitions, by showing how a new selective level can begin through evolution of individual characters, such as group size preference or dispersal tendency. The potential emergence of reliable cooperation via the co-evolution of individual cooperative and population-structuring behaviours demonstrates that groups of cooperating agents can create an environment in which they become so “locked in” to their group identity that the group warrants redescription as an individual in its own right. Consider the move from independent protozoans, to an intermediate cooperative stage as in slime moulds, to fully multi-cellular animals. Such creation of population structures that support cooperation parallels negotiation of a social contract. What are the philosophical implications of this perspective for understanding and explaining human social behaviour? On the one hand, it gives respectability and unique explanatory value to group-selectionist accounts. Explaining the origin of within-group cooperation and the origin of the groups themselves become part of the same project, which in turn means that we cannot understand social and cooperative behaviour in humans without understanding human population-structuring traits, e.g., living in family groups, group fission-fusion behaviours, migratory behaviours, etc. What will the explanations we seek look like? de Pinedo and Noble (2008) have argued that the description of evolved behaviour cannot be exclusively in mechanistic terms: we need both explanations that focus on an agent’s interaction with its environment, and explanations that focus on the physical or computational enabling conditions of such an interaction. In a context in which what counts as an agent is taken for granted, de Pinedo and Noble argue that both agent and sub-agent level explanations will be required. The perspective being outlined here forces an expansion of that position and reminds us that agency is not to be taken for granted; that it emerges from a lower level of organization after a history of selection brings simpler entities together in a coherent cooperative whole. The implication is that truly multi-level explanations will be necessary in the area of social behaviour. We explain the origin of the multi-cellular organism as the result of a cooperative merger of single-celled organisms, and we explain the origin of a super-organism such as an ant colony in a similar way. At each transition, the autonomous agents of the previous level become component mechanisms in the next, but no explanatory level can be entirely done away with. A human being is an example of a multi-cellular organism with a highly developed social aspect, occupying an intermediate point between radical individual independence and total group cohesion. To fully explain human behaviour, we need to know about the cellular machinery that enables personal-level agency. But we also need to know how human machinery fits together into families, communities and nations that will, at least partially, have their own emergent goals and purposes: “partially” because we are not yet a super-organism, of course. In conclusion, the perspective we outline suggests a view of the social contract as not at all unique to Hobbesian rational agents who have become tired of an insecure and violent lifestyle. Instead the ongoing negotiation of the social contract amongst ourselves can be seen as echoing earlier, now-successfully-concluded negotiations between the entities that became our genes and then our cells

Beyond persons: extending the personal / subpersonal distinction to non-rational animals and artificial agents

The distinction between personal level explanations and subpersonal ones has been subject to much debate in philosophy. We understand it as one between explanations that focus on an agent’s interaction with its environment, and explanations that focus on the physical or computational enabling conditions of such an interaction. The distinction, understood this way, is necessary for a complete account of any agent, rational or not, biological or artificial. In particular, we review some recent research in Artificial Life that pretends to do completely without the distinction, while using agent-centered concepts all the way. It is argued that the rejection of agent level explanations in favour of mechanistic ones is due to an unmotivated need to choose among representationalism and eliminativism. The dilemma is a false one if the possibility of a radical form of externalism is considered

Mortality and pulmonary complications in patients undergoing surgery with perioperative SARS-CoV-2 infection: an international cohort study

Background: The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on postoperative recovery needs to be understood to inform clinical decision making during and after the COVID-19 pandemic. This study reports 30-day mortality and pulmonary complication rates in patients with perioperative SARS-CoV-2 infection. Methods: This international, multicentre, cohort study at 235 hospitals in 24 countries included all patients undergoing surgery who had SARS-CoV-2 infection confirmed within 7 days before or 30 days after surgery. The primary outcome measure was 30-day postoperative mortality and was assessed in all enrolled patients. The main secondary outcome measure was pulmonary complications, defined as pneumonia, acute respiratory distress syndrome, or unexpected postoperative ventilation. Findings: This analysis includes 1128 patients who had surgery between Jan 1 and March 31, 2020, of whom 835 (74·0%) had emergency surgery and 280 (24·8%) had elective surgery. SARS-CoV-2 infection was confirmed preoperatively in 294 (26·1%) patients. 30-day mortality was 23·8% (268 of 1128). Pulmonary complications occurred in 577 (51·2%) of 1128 patients; 30-day mortality in these patients was 38·0% (219 of 577), accounting for 81·7% (219 of 268) of all deaths. In adjusted analyses, 30-day mortality was associated with male sex (odds ratio 1·75 [95% CI 1·28–2·40], p\textless0·0001), age 70 years or older versus younger than 70 years (2·30 [1·65–3·22], p\textless0·0001), American Society of Anesthesiologists grades 3–5 versus grades 1–2 (2·35 [1·57–3·53], p\textless0·0001), malignant versus benign or obstetric diagnosis (1·55 [1·01–2·39], p=0·046), emergency versus elective surgery (1·67 [1·06–2·63], p=0·026), and major versus minor surgery (1·52 [1·01–2·31], p=0·047). Interpretation: Postoperative pulmonary complications occur in half of patients with perioperative SARS-CoV-2 infection and are associated with high mortality. Thresholds for surgery during the COVID-19 pandemic should be higher than during normal practice, particularly in men aged 70 years and older. Consideration should be given for postponing non-urgent procedures and promoting non-operative treatment to delay or avoid the need for surgery. Funding: National Institute for Health Research (NIHR), Association of Coloproctology of Great Britain and Ireland, Bowel and Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society, European Society of Coloproctology, NIHR Academy, Sarcoma UK, Vascular Society for Great Britain and Ireland, and Yorkshire Cancer Research

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

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