Epistemic Vigilance

Humans massively depend on communication with others, but this leaves them open to the risk of being accidentally or intentionally misinformed. To ensure that, despite this risk, communication remains advantageous, humans have, we claim, a suite of cognitive mechanisms for epistemic vigilance. Here we outline this claim and consider some of the ways in which epistemic vigilance works in mental and social life by surveying issues, research and theories in different domains of philosophy, linguistics, cognitive psychology and the social sciences

Statistical treatment of looking-time data

Looking times (LTs) are frequently measured in empirical research on infant cognition. We analyzed the statistical distribution of LTs across participants in order to develop recommendations for their treatment in infancy research. Our analyses focused on a common within-subject experimental design, in which longer looking to novel or unexpected stimuli is predicted. We analyzed data from two sources: an in-house set of LTs that included data from individual participants (47 experiments, 1584 observations), and a representative set of published papers reporting group-level LT statistics (149 experiments from 33 papers). We established that LTs are log-normally distributed across participants, and therefore should always be log-transformed before parametric statistical analyses. We estimated the typical size of significant effects in LT studies, which allowed us to make recommendations about setting sample sizes. We show how our estimate of the distribution of effect sizes of LT studies can be used to design experiments to be analyzed by Bayesian statistics, where the experimenter is required to determine in advance the predicted effect size rather than the sample size. We demonstrate the robustness of this method in both sets of LT experiments.This work was supported by an Advanced Investigator Grant (OSTREFCOM) from the European Research Council

EFECTO DE EXTRACTOS ACUOSOS DEPhyllanthus sellowianusSOBRE LASPROPIEDADES VISCOELÁSTICAS DE GLÓBULOS ROJOS HUMANOS: ACTIVIDAD ANTIDIABÉTICA IN VITRO

Phyllanthus sellowianusMüll (Klotzch) Arg. is a native plant used for diabetes treatment. It is currently of interest to evaluate its activity on the mechanical properties of human red blood cells to elucidate its mechanism of action as an antidiabetic. For this, aqueous extracts were prepared by various extractive techniques. Using the Erythrocyte Rheometer, the in vitroeffect on the viscoelastic parameters of glycated human red blood cells, as occurs by hyperglycemiain diabetes, was evaluated. The results obtained from the treatment with the extracts show that they affect erythrocyte viscoelasticity and can reverse the glycation effects

Fenestrated-branched endovascular repair for distal thoracoabdominal aortic pathology after total aortic arch replacement with frozen elephant trunk

Objective: To report the outcomes of fenestrated-branched endovascular repair (FBEVAR) for thoracoabdominal aortic pathology after total aortic arch replacement with frozen elephant trunk (TAR+FET). Methods: Interrogation of prospectively maintained databases from four high-volume aortic centers identified consecutive patients treated with distal FBEVAR after prior TAR+FET between August 2013 and September 2020. The primary end point was 30-day/in-hospital mortality. Secondary end points were technical success, early clinical success, midterm survival, and freedom from reintervention. Data are presented as median (interquartile range). Results: A total of 39 patients (21 men; median age, 73 years [67-75 years]) with degenerative (n = 22) and postdissection thoracoabdominal aortic aneurysms (n = 17) (median diameter, 71 mm [61-78 mm]) were identified. Distal FBEVAR was intended in 27 patients (median interval, 9.8 months [6.2-16.6 months]), anticipated in 7, and unexpected in 5. A total of 31 patients had a two- (n = 24) or three-stage (n = 7) distal FBEVAR. Renovisceral target vessel preservation was 99.3% (145 of 146). Early primary and secondary technical success was 92% and 97%, respectively. Thirty-day mortality was 2.6% (n = 1; respiratory failure and spinal cord ischemia [SCI]). Six survivors also developed SCI, which was associated with complete (n = 4) or partial recovery (n = 2) at hospital discharge. No patients required renal replacement therapy or suffered a stroke. Early clinical success was 95%. Median follow-up was 30.5 months (23.7-49.7 months). Eleven patients required 16 late reinterventions. Estimated 3-year survival and freedom from reintervention were 84% ± 6% and 63% ± 10%, respectively. Conclusions: Distal FBEVAR after prior TAR+FET is associated with high technical success and low early mortality. The risk of SCI is significant although the majority of patients demonstrate full or partial recovery before hospital discharge. Midterm patient survival is favorable, but there remains a high requirement for late reintervention. FBEVAR represents an acceptable alternative to distal open thoracoabdominal aortic aneurysm repair

Genetic study of atypical femoral fractures using exome sequencing in three affected sisters and three unrelated patients

Objectives: Atypical femoral fractures (AFF) are rare, often related to long-term bisphosphonate (BPs) tre- atment. Their pathogenic mechanisms are not precisely known and there is no evidence to identify patients with a high risk of AFF. The aim of this work is to study the genetic bases of AFFs. Material and methods: Whole-exome sequencing was carried out on 3 sisters and 3 unrelated additional patients, all treated with BPs for more than 5 years. Low frequency, potentially pathogenic variants sha- red by the 3 sisters, were selected, were selected and a network of gene and protein interactions was constructed with the data found. Results: We identified 37 rare variants (in 34 genes) shared by the 3 sisters, some not previously descri- bed. The most striking variant was the p.Asp188Tyr mutation in the enzyme geranylgeranyl pyrophos- phate synthase (encoded by the GGPS1 gene), from the mevalonate pathway and essential for osteoclast function. Another noteworthy finding was two mutations (one in the 3 sisters and one in an unrelated patient) in the CYP1A1 gene, involved in the metabolism of steroids. We identified other variants that could also be involved in the susceptibility to AFFs or in the underlying osteoporotic phenotype, such as those present in the SYDE2, NGEF, COG4 and FN1 genes. Conclusions: Our data are compatible with a model where the accumulation of susceptibility variants could participate in the genetic basis of AFFs

Early-Life Critical Windows of Susceptibility to Manganese Exposure and Sex-Specific Changes in Brain Connectivity in Late Adolescence

Background: Early-life environmental exposures during critical windows (CWs) of development can impact life course health. Exposure to neuroactive metals such as manganese (Mn) during prenatal and early postnatal CWs may disrupt typical brain development, leading to persistent behavioral changes. Males and females may be differentially vulnerable to Mn, presenting distinctive CWs to Mn exposure. Methods: We used magnetic resonance imaging to investigate sex-specific associations between early-life Mn uptake and intrinsic functional connectivity in adolescence. A total of 71 participants (15-23 years old; 53% female) from the Public Health Impact of Manganese Exposure study completed a resting-state functional magnetic resonance imaging scan. We estimated dentine Mn concentrations at prenatal, postnatal, and early childhood periods using laser ablation-inductively coupled plasma-mass spectrometry. We performed seed-based correlation analyses to investigate the moderating effect of sex on the associations between Mn and intrinsic functional connectivity adjusting for age and socioeconomic status. Results: We identified significant sex-specific associations between dentine Mn at all time points and intrinsic functional connectivity in brain regions involved in cognitive and motor function: 1) prenatal: dorsal striatum, occipital/frontal lobes, and middle frontal gyrus; 2) postnatal: right putamen and cerebellum; and 3) early childhood: putamen and occipital, frontal, and temporal lobes. Network associations differed depending on exposure timing, suggesting that different brain networks may present distinctive CWs to Mn. Conclusions: These findings suggest that the developing brain is vulnerable to Mn exposure, with effects lasting through late adolescence, and that females and males are not equally vulnerable to these effects. Future studies should investigate cognitive and motor outcomes related to these associations