Pancreatic cancer intrinsic PI3Kα activity accelerates metastasis and rewires macrophage component.

Pancreatic ductal adenocarcinoma (PDAC) patients frequently suffer from undetected micro-metastatic disease. This clinical situation would greatly benefit from additional investigation. Therefore, we set out to identify key signalling events that drive metastatic evolution from the pancreas. We searched for a gene signature that discriminate localised PDAC from confirmed metastatic PDAC and devised a preclinical protocol using circulating cell-free DNA (cfDNA) as an early biomarker of micro-metastatic disease to validate the identification of key signalling events. An unbiased approach identified, amongst actionable markers of disease progression, the PI3K pathway and a distinctive PI3Kα activation signature as predictive of PDAC aggressiveness and prognosis. Pharmacological or tumour-restricted genetic PI3Kα-selective inhibition prevented macro-metastatic evolution by hindering tumoural cell migratory behaviour independently of genetic alterations. We found that PI3Kα inhibition altered the quantity and the species composition of the produced lipid second messenger PIP3 , with a selective decrease of C36:2 PI-3,4,5-P3 . Tumoural PI3Kα inactivation prevented the accumulation of pro-tumoural CD206-positive macrophages in the tumour-adjacent tissue. Tumour cell-intrinsic PI3Kα promotes pro-metastatic features that could be pharmacologically targeted to delay macro-metastatic evolution

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/)

Etude de la reproductibilité inter et intra-observateur de la mesure des variations respiratoires de la pression pulsée (delta Pp) en réanimation

POITIERS-BU Médecine pharmacie (861942103) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Virtualization in Automotive Embedded Systems : an Outlook

National audienc

Kite aerial photography : a low-cost method for monitoring seabird colonies

Obtaining aerial high-resolution images of bird nesting colonies using remote-sensing technology such as satellite-based remote sensing, manned aircraft, or Unmanned Aerial Vehicles might not be possible for many researchers due to financial constraints. Kite Aerial Photography (KAP) provides a possible low-cost alternative. We collected digital images of ground-nesting seabirds (i.e., cormorants and penguins) in two different ecosystems using a kite-based platform equipped with consumer-grade digital cameras with time-lapse capability to obtain estimates of breeding population size. KAP proved to be an efficient method for acquiring high-resolution aerial images. We obtained images of colonies of seabirds ranging in size from hundreds to several hundreds of thousands breeding pairs during flights lasting from a few minutes up to three hours, from flat to very steep areas, and in contrasted wind conditions (from 0.5 to 6 Beaufort force). KAP is an efficient low-cost method for acquiring high-resolution aerial images and an alternative to ground-based censuses, especially useful in rugged areas

Did the animal move? : a cross‑wavelet approach to geolocation data reveals year‑round whereabouts of a resident seabird

Considerable progress in our understanding of long-distance migration has been achieved thanks to the use of small geolocator devices (GLS). The tracking of resident or short-distance migrant animals remains however challenging because geolocation errors are substantial and difficult to estimate. This study aims to examine the sex-specific marine space uses of a resident tropical seabird, the masked booby (Sula dactylatra), during its full annual life cycle at the Fernando de Noronha archipelago (Brazil). Masked boobies (n = 31) tagged with GLS recording light intensity, seawater immersion, and water temperature showed a resident behaviour over their entire annual cycle. A wavelet analysis of GLS data revealed oscillatory patterns of inferred longitude correlated with changes in immersion frequency. This synchronicity demonstrated that birds traveled away and back from the colony on consecutive trips of short length ( ∼ 2–4 days) and short range ( ∼ 100–300 km) eastward of the colony. Duration and range of trips depended on the sex of the individual and on the time of the year. Trip duration increased gradually from the end of the breeding period to the post-breeding period, probably due to the release of the central-place breeding constraints. During the pre-breeding period, females had farther ranges eastward and spent more time in water than males. Despite inherent limits of light-based geolocation, this study demonstrates the relevance of synchronicity analysis of GLS data for investigating year-round movements of resident or short-distance migrants

Did the animal move? A cross-wavelet approach to geolocation data reveals year-round whereabouts of a resident seabird

Considerable progress in our understanding of long-distance migration has been achieved thanks to the use of small geolocator devices (GLS). The tracking of resident or short-distance migrant animals remains however challenging because geolocation errors are substantial and difficult to estimate. This study aims to examine the sex-specific marine space uses of a resident tropical seabird, the masked booby (Sula dactylatra), during its full annual life cycle at the Fernando de Noronha archipelago (Brazil). Masked boobies (n = 31) tagged with GLS recording light intensity, seawater immersion, and water temperature showed a resident behaviour over their entire annual cycle. A wavelet analysis of GLS data revealed oscillatory patterns of inferred longitude correlated with changes in immersion frequency. This synchronicity demonstrated that birds traveled away and back from the colony on consecutive trips of short length (∼ 2–4 days) and short range (∼ 100–300 km) eastward of the colony. Duration and range of trips depended on the sex of the individual and on the time of the year. Trip duration increased gradually from the end of the breeding period to the post-breeding period, probably due to the release of the central-place breeding constraints. During the pre-breeding period, females had farther ranges eastward and spent more time in water than males. Despite inherent limits of light-based geolocation, this study demonstrates the relevance of synchronicity analysis of GLS data for investigating year-round movements of resident or short-distance migrants