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ImportanceBefore surgery, the best strategy for managing patients who are taking renin-angiotensin system inhibitors (RASIs) (angiotensin-converting enzyme inhibitors or angiotensin receptor blockers) is unknown. The lack of evidence leads to conflicting guidelines.ObjectiveTo evaluate whether a continuation strategy vs a discontinuation strategy of RASIs before major noncardiac surgery results in decreased complications at 28 days after surgery.Design, setting, and participantsRandomized clinical trial that included patients who were being treated with a RASI for at least 3 months and were scheduled to undergo a major noncardiac surgery between January 2018 and April 2023 at 40 hospitals in France.InterventionPatients were randomized to continue use of RASIs (n = 1107) until the day of surgery or to discontinue use of RASIs 48 hours prior to surgery (ie, they would take the last dose 3 days before surgery) (n = 1115).Main outcomes and measuresThe primary outcome was a composite of all-cause mortality and major postoperative complications within 28 days after surgery. The key secondary outcomes were episodes of hypotension during surgery, acute kidney injury, postoperative organ failure, and length of stay in the hospital and intensive care unit during the 28 days after surgery.ResultsOf the 2222 patients (mean age, 67 years [SD, 10 years]; 65% were male), 46% were being treated with angiotensin-converting enzyme inhibitors at baseline and 54% were being treated with angiotensin receptor blockers. The rate of all-cause mortality and major postoperative complications was 22% (245 of 1115 patients) in the RASI discontinuation group and 22% (247 of 1107 patients) in the RASI continuation group (risk ratio, 1.02 [95% CI, 0.87-1.19]; P = .85). Episodes of hypotension during surgery occurred in 41% of the patients in the RASI discontinuation group and in 54% of the patients in the RASI continuation group (risk ratio, 1.31 [95% CI, 1.19-1.44]). There were no other differences in the trial outcomes.Conclusions and relevanceAmong patients who underwent major noncardiac surgery, a continuation strategy of RASIs before surgery was not associated with a higher rate of postoperative complications than a discontinuation strategy.Trial registrationClinicalTrials.gov Identifier: NCT03374449.

Alzheimer's disease (AD), the leading cause of dementia, has an estimated heritability of approximately 70%1. The genetic component of AD has been mainly assessed using genome-wide association studies, which do not capture the risk contributed by rare variants2. Here, we compared the gene-based burden of rare damaging variants in exome sequencing data from 32,558 individuals-16,036 AD cases and 16,522 controls. Next to variants in TREM2, SORL1 and ABCA7, we observed a significant association of rare, predicted damaging variants in ATP8B4 and ABCA1 with AD risk, and a suggestive signal in ADAM10. Additionally, the rare-variant burden in RIN3, CLU, ZCWPW1 and ACE highlighted these genes as potential drivers of respective AD-genome-wide association study loci. Variants associated with the strongest effect on AD risk, in particular loss-of-function variants, are enriched in early-onset AD cases. Our results provide additional evidence for a major role for amyloid-β precursor protein processing, amyloid-β aggregation, lipid metabolism and microglial function in AD.

Complement-mediated allograft injury, elicited by donor-specific HLA antibodies (DSA), is a defining pathophysiological characteristic of allograft damage. We aimed to study DSA-induced complement activation as a diagnostic marker of antibody-mediated rejection (AMR) and a risk stratification tool for graft loss in the context of lung transplantation (LT). We identified 38 DSA-positive patients whose serum samples were submitted for C3d deposition testing via the C3d assay. Among these 38 patients, 15 had AMR (DSAPos AMRPos ). Results were reported for each patient as the C3d ratio for each DSA, the immunodominant DSA, and the C3d ratio for all DSA present in a sample (C3d ratioSUM ). DSAPos AMRPos patients had higher C3d ratioSUM values (58.66 (-1.32 to 118.6) vs. 1.52 (0.30 to 2.74), P = 0.0016) and increased immunodominant C3d ratios (41.87 (1.72 to 82.02) vs. 0.69 (0.21 to 1.19), P = 0.001) when compared with DSAPos AMRNeg patients. Specificity and calculated positive predictive value of the immunodominant C3d ratio and BCMsum tests for AMR diagnosis were both 100% (CI = 17.4-100) in this cohort. Worst graft survival was associated with both immunodominant C3d ratio ≥4 or C3d ratioSUM ≥10 or BCMsum >7000, suggesting that the antibody composition and/or strength are the principal determinants of an HLA DSA's capacity to activate complement.

Anthropology was a founding member of cognitive science(Bender et al., 2010; Gardner, 1985), sharing with othercognitive disciplines a deep interest in thinking and behav-ior. With its unique expertise in the cultural content, con-text, and constitution of cognition, it would still be essentialto any comprehensive endeavor to explore the human mind(Bloch, 2012), but rather has turned into cognitive science’s“missing discipline” (Boden, 2006), thus leaving importantquestions unanswered or even unasked. Given that substan-tial shares of knowledge are implicit and that cognition issituated, distributed, embodied, and grounded in variousother ways, anthropological approaches provide privilegedaccess to investigation: for arriving at reasonable hypothe-ses, ensuring ecological validity, and even for coming upwith new research questions and paradigms (Astuti &Bloch, 2012; Hutchins, 2010; Nersessian, 2006).In line with recent calls for rapprochement in Topics inCognitive Science (Bender et al., 2012; Beller & Bender,2015), our symposium brings together scholars that repre-sent different branches of contemporary anthropology withdistinct perspectives—including ‘traditional’ social anthro-pology, cognitive anthropology and ethno-linguistics, cogni-tive ecology, evolutionary anthropology, and archaeology—to present what they consider to be indispensable contribu-tions to cognitive science.With our selection of authors, we hope to demonstrate thevalue of anthropological approaches for cognitive science aswell as the potential benefits of cross-disciplinary collabora-tion. Cognitive archaeologist Overmann discusses a theo-retical perspective on how mind, behavior, and materialartifacts interact to shape human cognition. Combining theirexpertise in linguistics and evolutionary anthropology, Ráczand Jordan investigate the design principles of kinship sys-tems as near-universal conceptual tools. With his back-ground in (ethno-)linguistics and cognitive anthropology,Le Guen uses Yucatec Maya sign languages to illustrate theimportance of cultural practices for shaping cognitive be-havior. Based on Hutchins’ cognitive ecology approach,Solberg speaks to questions at the intersection of anthropol-ogy and philosophy of science by illuminating the culturalframework of science production in a biology lab. And so-cial anthropologist Astuti concludes by taking a bird’s eyeview on how efforts to understand the human mind cruciallybenefit from acknowledging its historical origins and fromtaking the specific sociocultural contexts into consideration.Based on work some of which is published in high-qualityjournals (such as Science, Nature, PNAS, BBS, TiCS, Cur-rent Anthropology, or Cognition), these participants willoffer invaluable contributions to a more diverse, more inclu-sive, and hence more comprehensive cognitive science.