NOBEL, LE JEU DE LA DECOUVERTE SCIENTIFIQUE

Popper a rompu avec une tradition épistémologique ancienne en introduisant une dissymétrie entre vérifiabilité et réfutation. Cette conception a d'importantes répercussions sur la manière d'envisager la croissance des connaissances scientifiques et l'activité du chercheur. La vérité, qui avait pu être considérée comme un but pour la recherche scientifique, est placée hors d'atteinte. Sans indicateur évident pour marquer le terme de ses recherches, le chercheur doit alors faire, en fonction de ses motivations, un compromis entre l'exploration des théories possibles et des manières de les tester, et l'exploitation de théories qui auront été suffisamment corroborées. Si les thèses épistémologiques de Popper sont pertinentes, ce compromis exploration/exploitation au niveau du chercheur a des conséquences notables sur le développement des connaissances scientifiques et notamment, sur la fiabilité des théories acceptées. Ce sont ces conséquences que nous nous proposons d'étudier par une approche analytique, expérimentale et computationnelle, dont nous présentons ici les grandes lignes et les premiers résultats. Au delà de préoccupations purement épistémologiques, cette étude cherche à proposer un schéma générique pour l'approche d'un vaste ensemble de phénomènes d'élaboration collective et distribuée de connaissances ou d'artefacts.découverte collective, développement de la connaissance, compromis exploration/exploitation, épistemologie popperienne, knowledge managment distribué

An online database of infant functional near infraRed spectroscopy studies: a community-augmented systematic review

Until recently, imaging the infant brain was very challenging. Functional Near InfraRed Spectroscopy (fNIRS) is a promising, relatively novel technique, whose use is rapidly expanding. As an emergent field, it is particularly important to share methodological knowledge to ensure replicable and robust results. In this paper, we present a community-augmented database which will facilitate precisely this exchange. We tabulated articles and theses reporting empirical fNIRS research carried out on infants below three years of age along several methodological variables. The resulting spreadsheet has been uploaded in a format allowing individuals to continue adding new results, and download the most recent version of the table. Thus, this database is ideal to carry out systematic reviews. We illustrate its academic utility by focusing on the factors affecting three key variables: infant attrition, the reliability of oxygenated and deoxygenated responses, and signal-to-noise ratios. We then discuss strengths and weaknesses of the DBIfNIRS, and conclude by suggesting a set of simple guidelines aimed to facilitate methodological convergence through the standardization of reports

The Dichotomous Pattern of IL-12R and IL-23R Expression Elucidates the Role of IL-12 and IL-23 in Inflammation

IL-12 and IL-23 cytokines respectively drive Th1 and Th17 type responses. Yet, little is known regarding the biology of these receptors. As the IL-12 and IL-23 receptors share a common subunit, it has been assumed that these receptors are co-expressed. Surprisingly, we find that the expression of each of these receptors is restricted to specific cell types, in both mouse and human. Indeed, although IL-12Rβ2 is expressed by NK cells and a subset of γδ T cells, the expression of IL-23R is restricted to specific T cell subsets, a small number of B cells and innate lymphoid cells. By exploiting an IL-12- and IL-23-dependent mouse model of innate inflammation, we demonstrate an intricate interplay between IL-12Rβ2 NK cells and IL-23R innate lymphoid cells with respectively dominant roles in the regulation of systemic versus local inflammatory responses. Together, these findings support an unforeseen lineage-specific dichotomy in the in vivo role of both the IL-12 and IL-23 pathways in pathological inflammatory states, which may allow more accurate dissection of the roles of these receptors in chronic inflammatory diseases in humans

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

Extracorporeal Membrane Oxygenation for Severe Acute Respiratory Distress Syndrome associated with COVID-19: An Emulated Target Trial Analysis.

RATIONALE: Whether COVID patients may benefit from extracorporeal membrane oxygenation (ECMO) compared with conventional invasive mechanical ventilation (IMV) remains unknown. OBJECTIVES: To estimate the effect of ECMO on 90-Day mortality vs IMV only Methods: Among 4,244 critically ill adult patients with COVID-19 included in a multicenter cohort study, we emulated a target trial comparing the treatment strategies of initiating ECMO vs. no ECMO within 7 days of IMV in patients with severe acute respiratory distress syndrome (PaO2/FiO2 <80 or PaCO2 ≥60 mmHg). We controlled for confounding using a multivariable Cox model based on predefined variables. MAIN RESULTS: 1,235 patients met the full eligibility criteria for the emulated trial, among whom 164 patients initiated ECMO. The ECMO strategy had a higher survival probability at Day-7 from the onset of eligibility criteria (87% vs 83%, risk difference: 4%, 95% CI 0;9%) which decreased during follow-up (survival at Day-90: 63% vs 65%, risk difference: -2%, 95% CI -10;5%). However, ECMO was associated with higher survival when performed in high-volume ECMO centers or in regions where a specific ECMO network organization was set up to handle high demand, and when initiated within the first 4 days of MV and in profoundly hypoxemic patients. CONCLUSIONS: In an emulated trial based on a nationwide COVID-19 cohort, we found differential survival over time of an ECMO compared with a no-ECMO strategy. However, ECMO was consistently associated with better outcomes when performed in high-volume centers and in regions with ECMO capacities specifically organized to handle high demand. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/)

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

L'architecture fonctionnelle intégrant le contrôle cognitif et le contrôle motivationnel dans le cortex préfrontal humain.

The prefrontal cortex subserves executive function, the high-level cognitive ability that allows humans to generate behavior which does not depend only on external stimuli but also on internal goals. In this thesis we investigate the interaction between cognitive and motivational processes involved in executive function. We propose that the key concept to understand the functional architecture of lateral and medial prefrontal cortices is time-scale of information integration, which drives the fractionation of control processes along a caudo-rostral axis. Accordingly, posterior prefrontal regions drive immediate behavior adaptation on the basis of information conveyed by a stimulus and its context. Middle prefrontal regions are involved in maintaining over a series of trials a set of behavioural rules and processing their associated values. During a cognitive branching, the left and right medial prefrontal cortices can separately encode the values associated with delayed and ongoing task. The frontopolar region integrates these values and controls dual-task performance. Thus the functional properties of frontopolar and medial prefrontal cortices, despite being limited to the processing of two concurrent tasks, may play a critical role in the ability to generate complex behavior by coordinating ongoing task and future goals.Le cortex préfrontal est le siège de la fonction exécutive, la capacité cognitive de haut niveau qui permet aux humains d'agir non seulement en réaction aux stimuli externes mais aussi en fonction de buts internes. Dans cette thèse nous étudions l'interaction entre les processus cognitifs et motivationnels de la fonction exécutive. Nous proposons que le concept clef pour comprendre l'architecture fonctionnelle des cortex préfrontaux latéral et médian est la fenêtre temporelle d'intégration de l'information qui structure la séparation des processus de contrôle selon un axe caudo-rostral. Ainsi les régions préfrontales postérieures permettent l'adaptation du comportement immédiat sur la base des informations portées par le stimulus et son contexte. Les régions préfrontales moyennes sont impliquées dans le maitien d'un ensemble de règles comportementales et des valeurs qui leur sont associées au cours d'une même série d'essais. Pendant un embranchement cognitif, les cortex préfrontaux médians droit et gauche peuvent encoder séparément les valeurs associées à la tâche interrompue et à la tâche en cours. La région frontopolaire intègre ces valeurs et contrôle l'exécution d'une tâche double. Ainsi, les propriétés du cortex préfrontal médian et frontopolaire, qui limitent à deux le nombre de tâches conjointement traitées, pourraient néanmoins jouer un rôle fondamental dans la capacité à générer un comportement complexe en coordonnant la tâche présente et les buts futurs

Exploring brain activity in neuroeconomics

International audienceNeuroeconomics uses various methodologies to study the neural underpinning of economic decision-making. The goal of the present article is to briefly introduce the most frequently used methods. The main functioning, properties and features, including advantages and limits, of Positron Emission Tomography (PET), functional Magnetic Resonance Imaging (fMRI), Electroencephalography (EEG), Magnetoencephalography (MEG), and Transcranial Stimulation (TMS and tDCS) will be discussed

Exploring brain activity in neuroeconomics

Neuroeconomics uses various methodologies to study the neural underpinning of economic decision-making. The goal of the present article is to briefly introduce the most frequently used methods. The main functioning, properties and features, including advantages and limits, of Positron Emission Tomography (PET), functional Magnetic Resonance Imaging (fMRI), Electroencephalography (EEG), Magnetoencephalography (MEG), and Transcranial Stimulation (TMS and tDCS) will be discussed.neuroimaging, PET, fMRI, EEG, MEG, TMS, tDCS