IL-27 induces an IFN-like signature in murine macrophages which in turn modulate colonic epithelium

Mucosal delivery of IL-27 has been shown to have a therapeutic benefit in murine models of inflammatory bowel disease (IBD). The IL-27 effect was associated with phosphorylated STAT1 (pSTAT1), a product of IL27 receptor signaling, in bowel tissue. To determine whether IL-27 acted directly on colonic epithelium, murine colonoids and primary intact colonic crypts were shown to be unresponsive to IL-27 in vitro and to lack detectable IL-27 receptors. On the other hand, macrophages, which are present in inflamed colon tissue, were responsive to IL-27 in vitro. IL-27 induced pSTAT1 in macrophages, the transcriptome indicated an IFN-like signature, and supernatants induced pSTAT1 in colonoids. IL-27 induced anti-viral activity in macrophages and MHC Class II induction. We conclude that the effects of mucosal delivery of IL-27 in murine IBD are in part based on the known effects of IL27 inducing immunosuppression of T cells mediated by IL-10. We also conclude that IL-27 has potent effects on macrophages in inflamed colon tissue, generating mediators that in turn act on colonic epithelium

Supporting work practices through telehealth: impact on nurses in peripheral regions

<p>Abstract</p> <p>Background</p> <p>In Canada, workforce shortages in the health care sector constrain the ability of the health care system to meet the needs of its population and of its health care professionals. This issue is of particular importance in peripheral regions of Quebec, where significant inequalities in workforce distribution between regions has lead to acute nursing shortages and increased workloads. Information and communication technologies (ICTs) are innovative solutions that can be used to develop strategies to optimise the use of available resources and to design new nursing work practices. However, current knowledge is still limited about the real impact of ICTs on nursing recruitment and retention. Our aim is to better understand how work practice reorganization, supported by ICTs, and particularly by telehealth, may influence professional, educational, and organizational factors relating to Quebec nurses, notably those working in peripheral regions.</p> <p>Methods/Design</p> <p>First, we will conduct a descriptive study on the issue of nursing recruitment. Stratified sampling will be used to select approximately twenty innovative projects relating to the reorganization of work practices based upon ICTs. Semi-structured interviews with key informants will determine professional, educational, and organizational recruitment factors. The results will be used to create a questionnaire which, using a convenience sampling method, will be mailed to 600 third year students and recent graduates of two Quebec university nursing faculties. Descriptive, correlation, and hierarchical regression analyses will be performed to identify factors influencing nursing graduates' intentions to practice in peripheral regions. Secondly, we will conduct five case studies pertaining to the issue of nursing retention. Five ICT projects in semi-urban, rural, and isolated regions have been identified. Qualitative data will be collected through field observation and approximately fifty semi-structured interviews with key stakeholders.</p> <p>Discussion</p> <p>Data from both parts of this research project will be jointly analysed using triangulation of researchers, theoretical approaches, methods, and results. Continuous exchanges with decision makers and periodic knowledge transfer activities are planned to facilitate the dissemination and utilization of research results in policies regarding the nursing recruitment and retention.</p

Generalization optimizing machine learning to improve CT scan radiomics and assess immune checkpoint inhibitors’ response in non-small cell lung cancer: a multicenter cohort study

BackgroundRecent developments in artificial intelligence suggest that radiomics may represent a promising non-invasive biomarker to predict response to immune checkpoint inhibitors (ICIs). Nevertheless, validation of radiomics algorithms in independent cohorts remains a challenge due to variations in image acquisition and reconstruction. Using radiomics, we investigated the importance of scan normalization as part of a broader machine learning framework to enable model external generalizability to predict ICI response in non-small cell lung cancer (NSCLC) patients across different centers.MethodsRadiomics features were extracted and compared from 642 advanced NSCLC patients on pre-ICI scans using established open-source PyRadiomics and a proprietary DeepRadiomics deep learning technology. The population was separated into two groups: a discovery cohort of 512 NSCLC patients from three academic centers and a validation cohort that included 130 NSCLC patients from a fourth center. We harmonized images to account for variations in reconstruction kernel, slice thicknesses, and device manufacturers. Multivariable models, evaluated using cross-validation, were used to estimate the predictive value of clinical variables, PD-L1 expression, and PyRadiomics or DeepRadiomics for progression-free survival at 6 months (PFS-6).ResultsThe best prognostic factor for PFS-6, excluding radiomics features, was obtained with the combination of Clinical + PD-L1 expression (AUC = 0.66 in the discovery and 0.62 in the validation cohort). Without image harmonization, combining Clinical + PyRadiomics or DeepRadiomics delivered an AUC = 0.69 and 0.69, respectively, in the discovery cohort, but dropped to 0.57 and 0.52, in the validation cohort. This lack of generalizability was consistent with observations in principal component analysis clustered by CT scan parameters. Subsequently, image harmonization eliminated these clusters. The combination of Clinical + DeepRadiomics reached an AUC = 0.67 and 0.63 in the discovery and validation cohort, respectively. Conversely, the combination of Clinical + PyRadiomics failed generalizability validations, with AUC = 0.66 and 0.59.ConclusionWe demonstrated that a risk prediction model combining Clinical + DeepRadiomics was generalizable following CT scan harmonization and machine learning generalization methods. These results had similar performances to routine oncology practice using Clinical + PD-L1. This study supports the strong potential of radiomics as a future non-invasive strategy to predict ICI response in advanced NSCLC

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/)

Étude quantitative du temps d’exposition aux écrans chez les enfants âgés de 3 à 6 ans dans un quartier du Havre

Les écrans sont devenus omniprésents dans les foyers avec une exposition dès le plus jeune âge alors que les dernières études à ce sujet tendent à montrer des effets néfastes d’une exposition précoce. Les pouvoirs publics, sociétés savantes, associations de parents se mobilisent depuis plusieurs années pour alerter le public sur ces dangers avec la mise en place de recommandations pour limiter et accompagner l’usage des écrans. L’objectif de l’étude est de quantifier l’exposition aux écrans des enfants en âge préscolaire. Matériel et méthode : Étude quantitative réalisée dans un quartier prioritaire d’éducation, ciblant les 3 à 6 ans scolarisés. Des questionnaires papier ont été distribués à l’intention des parents. Résultats : 363 questionnaires valides ont été recueillis sur les 880 distribués. 46,3% des enfants regardent plus de 1 heure les écrans les jours d’école et ce chiffre atteint les 75,2% les jours sans école dont 25,3% regardent les écrans avant d’aller dormir. L’utilisation de la télévision prédomine les autres écrans avec 64,5% des enfants la regardant les jours d’école et 86,8% le week-end. 25,3% des enfants possèdent un écran dans leur chambre ; 61,2 % prennent leur repas devant la télévision ; 35,3% regardent les écrans seuls et dans 52,9% des cas il s’agit de programmes inadaptés à leur âge. 37,7% des parents estiment que ce temps est jugé excessif.Discussion : Les temps d’écrans semblent concordants avec les autres études. Conclusion : Les recommandations de « bon usage » des écrans à destination des parents pour les enfants restent encore peu suivies avec un temps d’exposition et un usage de ces écrans inadaptés pour les enfants âgés de 3 à 6 ans

Nuclear Heating Measurements in Material Testing Reactor: A Comparison Between a Differential Calorimeter and a Gamma Thermometer

International audienceNuclear heating measurements in Material Testing Reactors are crucial for the design of the experimental devices and the prediction of the temperature of the hosted samples. Indeed, nuclear heating is a key input data for the computer codes which simulate temperature reached by samples under irradiation. In the Jules Horowitz Reactor under construction at the CEA Cadarache, the maximal expected nuclear heating levels will be about 15 to 18 W/g and it will be necessary to measure this key parameter with the best accuracy. An experiment was led at the OSIRIS reactor to compare the measurements between the two most appropriate sensors for measuring nuclear heating in MTR; a differential calorimeter and a gamma thermometer. A specific differential calorimeter was designed for low nuclear heating and a standard gamma thermometer was used. Experimental results and Monte-Carlo simulations show that the two sensors are suitable even if the measured energy deposit is different in the two sensors. Finally, these comparisons between the measurements recall that it is primordial to precise in which material and environment the nuclear heating is measured to use this key parameter for designing experimental devices in MTR

Functional dedifferentiation and reduced task-related deactivations underlie the age-related decline of prospective memory

International audienceProspective memory (PM) refers to the ability to remember to execute an intention atthe appropriate moment in the future, which can be performed either at the appearance of anevent (event-based, EBPM) or after a certain amount of time (time-based, TBPM). PM isgenerally impaired during aging but the cerebral substrates of this decline have been littleinvestigated. Using functional Magnetic Resonance Imaging (fMRI), we investigated theneural bases of PM in 20 young and 20 healthy older adults. They were proposed a task ofsemantic categorisation of pictures (ongoing task). For some blocks, participants only had toperform this ongoing task while, for others, a PM instruction was added. In this case, asupplementary answer in response to a specific colour of border for EBPM or at specific timeintervals for TBPM was expected. PM, and more particularly TBPM, declined in older adults.For both PM conditions, older adults recruited additional brain areas, but also showedreduced deactivations of other regions. These results are discussed in light of models of theaging brain

pH controls spermatozoa motility in the Pacific oyster (Crassostrea gigas)

Investigating the roles of chemical factors stimulating and inhibiting sperm motility is required to understand the mechanisms of spermatozoa movement. In this study, we described the composition of the seminal fluid (osmotic pressure, pH, and ions) and investigated the roles of these factors and salinity in initiating spermatozoa movement in the Pacific oyster, Crassostrea gigas. The acidic pH of the gonad (5.82±0.22) maintained sperm in the quiescent stage and initiation of flagellar movement was triggered by a sudden increase of spermatozoa external pH (pHe) when released in seawater (SW). At pH 6.4, percentage of motile spermatozoa was three times higher when they were activated in SW containing 30 mM NH4Cl, which alkalinizes internal pH (pHi) of spermatozoa, compared to NH4Cl-free SW, revealing the role of pHi in triggering sperm movement. Percentage of motile spermatozoa activated in Na+-free artificial seawater (ASW) was highly reduced compared to ASW, suggesting that change of pHi triggering sperm motility was mediated by a Na+/H+ exchanger. Motility and swimming speed were highest in salinities between 33.8 and 42.7‰ (within a range of 0 to 50 ‰), and pH values above 7.5 (within a range of 4.5 to 9.5)