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"Girard, Geoffrey"
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Project Cain
Fifteen-year-old Jeff Jacobson learns that not only was he cloned from infamous serial killer Jeffrey Dahmer's blood as part of a top-secret government experiment, but there are other clones like him and he is the only one who can track them down before it is too late.
Book
Long-term IL-33–producing epithelial progenitor cells in chronic obstructive lung disease
Chronic obstructive lung disease is characterized by persistent abnormalities in epithelial and immune cell function that are driven, at least in part, by infection. Analysis of parainfluenza virus infection in mice revealed an unexpected role for innate immune cells in IL-13-dependent chronic lung disease, but the upstream driver for the immune axis in this model and in humans with similar disease was undefined. We demonstrate here that lung levels of IL-33 are selectively increased in postviral mice with chronic obstructive lung disease and in humans with very severe chronic obstructive pulmonary disease (COPD). In the mouse model, IL-33/IL-33 receptor signaling was required for Il13 and mucin gene expression, and Il33 gene expression was localized to a virus-induced subset of airway serous cells and a constitutive subset of alveolar type 2 cells that are both linked conventionally to progenitor function. In humans with COPD, IL33 gene expression was also associated with IL13 and mucin gene expression, and IL33 induction was traceable to a subset of airway basal cells with increased capacities for pluripotency and ATP-regulated release of IL-33. Together, these findings provide a paradigm for the role of the innate immune system in chronic disease based on the influence of long-term epithelial progenitor cells programmed for excess IL-33 production.
Journal Article
Transpulmonary pressure in SARS-CoV-2-associated acute respiratory distress syndrome: a single-center observational study
[...]high levels of PEEP may lead to lung overdistension associated with an increase of alveolar dead space and an alteration of gas exchanges. All consecutive ARDS adult patients with confirmed Covid-19 admitted in our critical care unit are included if they received invasive mechanical. [...]identification of respiratory phenotype seems therefore essential in ventilated SARS-CoV-2 patients to determine optimal mechanical ventilation strategy.
Journal Article
Impact of lumbar cerebrospinal fluid drainage to control intracranial hypertension in patients with severe traumatic brain injury: a retrospective monocentric cohort
Background
External lumbar drainage (ELD) of cerebrospinal fluid may help control intracranial pressure following a traumatic brain injury. We aimed to assess the efficacy and safety of ELD in post-traumatic intracranial hypertension (IH).
Methods
This retrospective monocentric cohort study was conducted in the trauma critical care unit of the regional Level-I trauma centre between January 2012 and December 2022. All traumatic brain injury patients with IH (≥ 22 mmHg despite optimal sedation) were included. Data collection focused on the duration and management of IH, complications related to ELD, and outcomes (6-month Glasgow Outcome Scale [GOS]). The influence of ELD on the duration of IH was assessed using a multivariable Cox regression analysis, while its impact on the 6-month GOS (“unfavourable outcome” GOS 1–3, “good outcome” GOS 4–5) was evaluated using a multivariable logistic regression analysis.
Results
Ninety patients (mean age 37 [SD, 16], injury severity score [ISS] 29 [IQR, 24–34]) were analyzed during the study period. Of these, 50 (56%) benefited from an ELD during their hospitalization (
ELD
group). The IH duration was significantly reduced in the
ELD
group (hazard ratio [HR] 1.74 [95% confidence interval (CI) 1.05–2.87;
p
= 0.03]). One patient (2%) experienced a cerebral herniation following ELD placement, and two others (4%) developed device-associated meningitis. The
ELD
group was significantly associated with a lower likelihood of an unfavourable outcome (OR 0.32 [95% CI 0.13–0.77];
p
= 0.011) compared to the
no ELD
group.
Conclusion
ELD appears in our cohort to be a safe and effective strategy to control post-traumatic IH, with an acceptable benefit-risk ratio. Our analysis even suggests a potential outcome improvement in patients treated by ELD compared with those having no cerebrospinal fluid drainage.
Journal Article
Mathematical modelling of oxygenation under veno-venous ECMO configuration using either a femoral or a bicaval drainage
BackgroundThe bicaval drainage under veno-venous extracorporeal membrane oxygenation (VV ECMO) was compared in present experimental study to the inferior caval drainage in terms of systemic oxygenation.MethodTwo mathematical models were built to simulate the inferior vena cava-to-right atrium (IVC → RA) route and the bicaval drainage-to-right atrium return (IVC + SVC → RA) route using the following parameters: cardiac output (QC), IVC flow/QC ratio, venous oxygen saturation, extracorporeal pump flow (QEC), and pulmonary shunt (PULM-Shunt) to obtain pulmonary artery oxygen saturation (SPAO2) and systemic blood oxygen saturation (SaO2).ResultsWith the IVC → RA route, SPAO2 and SaO2 increased linearly with QEC/QC until the threshold of the IVC flow/QC ratio, beyond which the increase in SPAO2 reached a plateau. With the IVC + SVC → RA route, SPAO2 and SaO2 increased linearly with QEC/QC until 100% with QEC/QC = 1. The difference in required QEC/QC between the two routes was all the higher as SaO2 target or PULM-Shunt were high, and occurred all the earlier as PULM-Shunt were high. The required QEC between the two routes could differ from 1.0 L/min (QC = 5 L/min) to 1.5 L/min (QC = 8 L/min) for SaO2 target = 90%. Corresponding differences of QEC for SaO2 target = 94% were 4.7 L/min and 7.9 L/min, respectively.ConclusionBicaval drainage under ECMO via the IVC + SVC → RA route gave a superior systemic oxygenation performance when both QEC/QC and pulmonary shunt were high. The VV-V ECMO configuration (IVC + SVC → RA route) might be an attractive rescue strategy in case of refractory hypoxaemia under VV ECMO.
Journal Article
Direct U–Pb dating of carbonates from micron-scale femtosecond laser ablation inductively coupled plasma mass spectrometry images using robust regression
Uranium–lead (U–Pb) dating of carbonates by laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) spot analysis is an increasingly used method in the field of geosciences, as it brings very strong constraints over the geological history of basins, faults or reservoirs. Most ages currently published are based on the measurement of U and Pb ratios on spot ablations, using nanosecond lasers coupled to sector field or multi-collector ICP-MS. Here, we test a new strategy for the U–Pb dating of carbonates from 2D isotopic ratio maps, based on the use of a robust regression approach in the data reduction workflow. The isotopic maps, with a minimum area of 0.65 mm2 (∼ 1000 pixels of 13×25 µm resolution), are obtained using a 257 nm femtosecond laser ablation system at a high repetition rate (500 Hz) coupled to a high-resolution ICP-MS. The maps commonly show significant variations in isotope ratios at the pixel scale, allowing the plotting of pixel U–Pb ratios in concordia or isochron diagrams and the calculation of U–Pb ages. Due to the absence of individual ratio uncertainties, the ages are calculated using MM-robust linear regression rather than the more commonly used York-type regression. The goodness of fit to the data is assessed by the calculation of the residual standard error (RSE) of the regression and by the calculation of a mean square of weight deviates (MSWD) on discretised data. Several examples are provided that compare the ages calculated by robust regression with those obtained by other techniques (e.g. isotope dilution, LA-ICP-MS spot analyses and the pixel-pooling approach). For most samples, characterised by high U concentrations (> 1 ppm), robust regression allows for the calculation of ages and uncertainties similar to those obtained with the other approaches. However, for samples with lower U concentrations (< 0.5 ppm), the ages obtained are up to 10 % too young due to pixels with high U ∕ Pb acting as leverage points for the regression. We conclude that the U–Pb ages calculated by the regression method tested here, although statistically robust, should be critically analysed before validation, especially for samples with low U concentrations.
Journal Article
Not all quiet on the noise front
Phenotypic diversity exists even within isogenic populations of cells. Such nongenetic individuality may have wide implications for our understanding of many biological processes. The field of study concerned with the investigation of nongenetic individuality, also known as the 'biology of noise', is ripe with exciting scientific opportunities and challenges.
Journal Article
LARD 2.0: Enhanced Datasets and Benchmarking for Autonomous Landing Systems
This paper addresses key challenges in the development of autonomous landing systems, focusing on dataset limitations for supervised training of Machine Learning (ML) models for object detection. Our main contributions include: (1) Enhancing dataset diversity, by advocating for the inclusion of new sources such as BingMap aerial images and Flight Simulator, to widen the generation scope of an existing dataset generator used to produce the dataset LARD; (2) Refining the Operational Design Domain (ODD), addressing issues like unrealistic landing scenarios and expanding coverage to multi-runway airports; (3) Benchmarking ML models for autonomous landing systems, introducing a framework for evaluating object detection subtask in a complex multi-instances setting, and providing associated open-source models as a baseline for AI models' performance.
Paper