Morphodynamique de la zone de "swash" : étude en canal à houle par une méthode de stéréoscopie optique

Ce travail porte sur l’étude de l’évolution morphologique dans la zone de swash à haute résolution spatiale et temporelle afin de pouvoir analyser l’influence de la houle. Cette étude s’appuie sur deux campagnes de mesures menées dans le grand canal à houle CIEM (Barcelone), l’une avec application d’un forçage aléatoire érosif de type JONSWAP et l’autre avec application d’une série de forçages bichromatiques. L’originalité de l’étude proposée ici consiste en l’analyse, par une méthode de stéréoscopie optique, de l’évolution du fond avec une excellente précision tout en quantifiant précisément l’évolution des fronts d’eau sur une surface continue, la majorité des techniques de mesure ne donnant en général accès qu’à des relevés ponctuels dans cette zone. La position du lit de sable est estimée avec une précision de quelques centaines de μm. Sur des temps longs, le forçage JONSWAP érosif engendre un recul global et quasi-homogène dans la zone de swash. Cependant, cette évolution ne semble pas influencer la réponse hydrodynamique qui reste similaire dans la zone de swash lorsque l’on répète la série. Ceci a été confirmé dans le cas des forçages bichromatiques, répétés sur des fonds différents. Au sein d’une série d’un forçage aléatoire, différentes échelles de temps sont observées : l’échelle gravitaire (période caractéristique du signal) et les ondes infragravitaires (large gamme d’événements plus longs). Cette coexistence de plusieurs échelles de temps a pu être associée à la forte variabilité du profil de plage, notamment dans la direction cross-shore. Le cas bichromatique montre quant à lui une convergence du profil de plage vers un état qui ne dépendrait que du forçage en entrée. L’interaction d’une seule onde infragravitaire avec l’onde gravitaire ne peut donc pas être responsable de la variabilité du fond observée avec le forçage aléatoire. En revanche, cette étude semble confirmer la présence d’événements particuliers à l’origine d’une forte modification du fond sableux. Le lien entre ces événements et l’interaction entre des événements hydrodynamiques spécifiques et la forme du fond n’est pas encore complètement établi. Enfin, pour le forçage aléatoire la variabilité transverse induite par les ondes courtes est forte alors qu’elle semble plus faible à l’échelle de l’onde longue. Pour le forçage bichromatique, cette variabilité transverse a également pu être observée mais son lien avec le forçage reste encore à élucider. ABSTRACT : This study investigates the morphological evolution in the swash zone at high spatial and temporal resolution to be able to analyze the swell influence. The study is here based on two measurement campaigns in the large CIEM wave flume (Barcelona), using both a random erosive JONSWAP and bichromatics forcing. The originality of the proposed study lies on analysis, by an optical stereoscopic method, of bottom evolution with a very good precision while getting an accurate quantification of water fronts evolution on a continuous area, most of the measurement techniques generally allowing only to obtain punctual measurements in this area. The sand bed position is estimated with an accuracy of a few hundred μm. Over long periods, erosive JONSWAP forcing generates an overall and almost homogeneous backward movement in the swash area. However, this trend does not appear to influence the hydrodynamics response that remains similar in the swash area when the series is repeated. This was confirmed in the bichromatic forcings case, repeated on different bottoms. During a random forcing series, different time scales are observed : the gravity scale (characteristic period of the signal) and infragravity waves (wide range of longer events). This coexistence of several time scales could be associated with the observation of a strong variability of the beach profile, especially in the cross-shore direction. The bichromatic case shows meanwhile convergence of beach profile to a state that would depend only on forcing conditions. The interaction of a single infragravity wave with the gravitational wave can therefore not be responsible for the observed bottom variability with the random forcing. In contrast, the present study seems to confirm the presence of specific events responsible of a strong change in the sandy bottom. The link between these events and the hydrodynamic interaction between specific events and the bottom shape is not yet completely established. Finally, for the random forcing the transverse variability induced by short wave is strong as it seems weak at long wave time scale. For bichromatic forcing, the transverse variability has also been observed but its link with the forcing still remains to be elucidated

Investigation of the swash zone evolution at wave time scale

The present work is dedicated to the study of the swash zone bed evolution at a high temporal and spatial resolution to investigate single-wave to wave-group time scales. The measurements are obtained in a large scale wave flume with a 1/15 sloping beach of well-sorted sand (d₅₀= 250 μm). The wave regime considered is a random Jonswap spectrum (peak enhancement factor γ = 3.3, significant wave height Hₛ= 0.53 m and peak period Tₚ = 4.14 s). A stereoscopic technique (Astruc et al., 2012) has been used to measure the sand bed evolution in the swash zone over a 3×2 m² area. This experiment allows us to capture the swash dynamics and the bottom evolution at the different temporal scales. The results prove the strong correlation between wave forcing and swash zone response over the entire experiment, even if the bottom evolves. At shorter time scales, we can observe the signature of gravity and infragravity waves. We showed that at both time scales, the erosion process exhibits a strong variability in time as accretion and erosion events are observed. The spatial variability of the bottom evolution is stronger at gravity than at infragravity time scales. These results reinforce the now-admitted idea that the mean evolution of the sand bed in the swash zone is the result of several events of a very different nature, which themselves depend on the details of the swash hydrodynamics

Utilization of mechanical power and associations with clinical outcomes in brain injured patients: a secondary analysis of the extubation strategies in neuro-intensive care unit patients and associations with outcome (ENIO) trial

Background: There is insufficient evidence to guide ventilatory targets in acute brain injury (ABI). Recent studies have shown associations between mechanical power (MP) and mortality in critical care populations. We aimed to describe MP in ventilated patients with ABI, and evaluate associations between MP and clinical outcomes. Methods: In this preplanned, secondary analysis of a prospective, multi-center, observational cohort study (ENIO, NCT03400904), we included adult patients with ABI (Glasgow Coma Scale ≤ 12 before intubation) who required mechanical ventilation (MV) ≥ 24 h. Using multivariable log binomial regressions, we separately assessed associations between MP on hospital day (HD)1, HD3, HD7 and clinical outcomes: hospital mortality, need for reintubation, tracheostomy placement, and development of acute respiratory distress syndrome (ARDS). Results: We included 1217 patients (mean age 51.2 years [SD 18.1], 66% male, mean body mass index [BMI] 26.3 [SD 5.18]) hospitalized at 62 intensive care units in 18 countries. Hospital mortality was 11% (n = 139), 44% (n = 536) were extubated by HD7 of which 20% (107/536) required reintubation, 28% (n = 340) underwent tracheostomy placement, and 9% (n = 114) developed ARDS. The median MP on HD1, HD3, and HD7 was 11.9 J/min [IQR 9.2-15.1], 13 J/min [IQR 10-17], and 14 J/min [IQR 11-20], respectively. MP was overall higher in patients with ARDS, especially those with higher ARDS severity. After controlling for same-day pressure of arterial oxygen/fraction of inspired oxygen (P/F ratio), BMI, and neurological severity, MP at HD1, HD3, and HD7 was independently associated with hospital mortality, reintubation and tracheostomy placement. The adjusted relative risk (aRR) was greater at higher MP, and strongest for: mortality on HD1 (compared to the HD1 median MP 11.9 J/min, aRR at 17 J/min was 1.22, 95% CI 1.14-1.30) and HD3 (1.38, 95% CI 1.23-1.53), reintubation on HD1 (1.64; 95% CI 1.57-1.72), and tracheostomy on HD7 (1.53; 95%CI 1.18-1.99). MP was associated with the development of moderate-severe ARDS on HD1 (2.07; 95% CI 1.56-2.78) and HD3 (1.76; 95% CI 1.41-2.22). Conclusions: Exposure to high MP during the first week of MV is associated with poor clinical outcomes in ABI, independent of P/F ratio and neurological severity. Potential benefits of optimizing ventilator settings to limit MP warrant further investigation

Swash zone morphodynamics : wave flume investigation by an optical stereoscopic method

Ce travail porte sur l’étude de l’évolution morphologique dans la zone de swash à haute résolution spatiale et temporelle afin de pouvoir analyser l’influence de la houle. Cette étude s’appuie sur deux campagnes de mesures menées dans le grand canal à houle CIEM (Barcelone), l’une avec application d’un forçage aléatoire érosif de type JONSWAP et l’autre avec application d’une série de forçages bichromatiques. L’originalité de l’étude proposée ici consiste en l’analyse, par une méthode de stéréoscopie optique, de l’évolution du fond avec une excellente précision tout en quantifiant précisément l’évolution des fronts d’eau sur une surface continue, la majorité des techniques de mesure ne donnant en général accès qu’à des relevés ponctuels dans cette zone. La position du lit de sable est estimée avec une précision de quelques centaines de μm. Sur des temps longs, le forçage JONSWAP érosif engendre un recul global et quasi-homogène dans la zone de swash. Cependant, cette évolution ne semble pas influencer la réponse hydrodynamique qui reste similaire dans la zone de swash lorsque l’on répète la série. Ceci a été confirmé dans le cas des forçages bichromatiques, répétés sur des fonds différents. Au sein d’une série d’un forçage aléatoire, différentes échelles de temps sont observées : l’échelle gravitaire (période caractéristique du signal) et les ondes infragravitaires (large gamme d’événements plus longs). Cette coexistence de plusieurs échelles de temps a pu être associée à la forte variabilité du profil de plage, notamment dans la direction cross-shore. Le cas bichromatique montre quant à lui une convergence du profil de plage vers un état qui ne dépendrait que du forçage en entrée. L’interaction d’une seule onde infragravitaire avec l’onde gravitaire ne peut donc pas être responsable de la variabilité du fond observée avec le forçage aléatoire. En revanche, cette étude semble confirmer la présence d’événements particuliers à l’origine d’une forte modification du fond sableux. Le lien entre ces événements et l’interaction entre des événements hydrodynamiques spécifiques et la forme du fond n’est pas encore complètement établi. Enfin, pour le forçage aléatoire la variabilité transverse induite par les ondes courtes est forte alors qu’elle semble plus faible à l’échelle de l’onde longue. Pour le forçage bichromatique, cette variabilité transverse a également pu être observée mais son lien avec le forçage reste encore à élucider.This study investigates the morphological evolution in the swash zone at high spatial and temporal resolution to be able to analyze the swell influence. The study is here based on two measurement campaigns in the large CIEM wave flume (Barcelona), using both a random erosive JONSWAP and bichromatics forcing. The originality of the proposed study lies on analysis, by an optical stereoscopic method, of bottom evolution with a very good precision while getting an accurate quantification of water fronts evolution on a continuous area, most of the measurement techniques generally allowing only to obtain punctual measurements in this area. The sand bed position is estimated with an accuracy of a few hundred μm. Over long periods, erosive JONSWAP forcing generates an overall and almost homogeneous backward movement in the swash area. However, this trend does not appear to influence the hydrodynamics response that remains similar in the swash area when the series is repeated. This was confirmed in the bichromatic forcings case, repeated on different bottoms. During a random forcing series, different time scales are observed : the gravity scale (characteristic period of the signal) and infragravity waves (wide range of longer events). This coexistence of several time scales could be associated with the observation of a strong variability of the beach profile, especially in the cross-shore direction. The bichromatic case shows meanwhile convergence of beach profile to a state that would depend only on forcing conditions. The interaction of a single infragravity wave with the gravitational wave can therefore not be responsible for the observed bottom variability with the random forcing. In contrast, the present study seems to confirm the presence of specific events responsible of a strong change in the sandy bottom. The link between these events and the hydrodynamic interaction between specific events and the bottom shape is not yet completely established. Finally, for the random forcing the transverse variability induced by short wave is strong as it seems weak at long wave time scale. For bichromatic forcing, the transverse variability has also been observed but its link with the forcing still remains to be elucidated

Sistema Alimentario y Salud: Impactos, desafíos y alternativas

Participantes: Marie Christine Renard, moderadora. Jessica Tolentino, organizadora de la sesión. Marta Astier, investigadora de la Universidad Autónoma de México. Agustín Rojas, profesor de la Universidad Autónoma de México. Cecilia Elizondo, representante de ECOSUR. Edelmira Linares Mazari, Instituto de Biología (UNAM). Robert Bye, expositor.Temas: Sistema Alimentario. Desafíos ambientales y sociales. Estructura alimentaria

La déficience de PBRM1 confère une létalité synthétique aux inhibiteurs de la réparation de l'ADN dans le cancer

International audienceInactivation of Polybromo 1 (PBRM1), a specific subunit of the PBAF chromatin remodeling complex, occurs frequently in cancer, including 40% of clear cell renal cell carcinomas (ccRCC). To identify novel therapeutic approaches to targeting PBRM1-defective cancers, we used a series of orthogonal functional genomic screens that identified PARP and ATR inhibitors as being synthetic lethal with PBRM1 deficiency. The PBRM1/PARP inhibitor synthetic lethality was recapitulated using several clinical PARP inhibitors in a series of in vitro model systems and in vivo in a xenograft model of ccRCC. In the absence of exogenous DNA damage, PBRM1-defective cells exhibited elevated levels of replication stress, micronuclei, and R-loops. PARP inhibitor exposure exacerbated these phenotypes. Quantitative mass spectrometry revealed that multiple R-loop processing factors were downregulated in PBRM1-defective tumor cells. Exogenous expression of the R-loop resolution enzyme RNase H1 reversed the sensitivity of PBRM1-deficient cells to PARP inhibitors, suggesting that excessive levels of R-loops could be a cause of this synthetic lethality. PARP and ATR inhibitors also induced cyclic GMP-AMP synthase/stimulator of interferon genes (cGAS/STING) innate immune signaling in PBRM1-defective tumor cells. Overall, these findings provide the preclinical basis for using PARP inhibitors in PBRM1-defective cancers. SIGNIFICANCE: This study demonstrates that PARP and ATR inhibitors are synthetic lethal with the loss of PBRM1, a PBAF-specific subunit, thus providing the rationale for assessing these inhibitors in patients with PBRM1-defective cancer.L'inactivation de Polybromo 1 (PBRM1), une sous-unité spécifique du complexe de remodelage de la chromatine PBAF, se produit fréquemment dans le cancer, y compris dans 40% des carcinomes rénaux à cellules claires (ccRCC). Afin d'identifier de nouvelles approches thérapeutiques pour cibler les cancers déficients en PBRM1, nous avons utilisé une série de cribles génomiques fonctionnels orthogonaux qui ont identifié les inhibiteurs PARP et ATR comme étant synthétiquement létaux en cas de déficience en PBRM1. La létalité synthétique des inhibiteurs de PBRM1/PARP a été récapitulée en utilisant plusieurs inhibiteurs cliniques de PARP dans une série de systèmes modèles in vitro et in vivo dans un modèle de xénogreffe de ccRCC. En l'absence de lésions exogènes de l'ADN, les cellules déficientes en PBRM1 présentaient des niveaux élevés de stress de réplication, de micronoyaux et de boucles R. L'exposition à un inhibiteur de PARP a exacerbé la létalité synthétique. L'exposition à un inhibiteur de PARP a exacerbé ces phénotypes. La spectrométrie de masse quantitative a révélé que plusieurs facteurs de traitement des boucles R étaient régulés à la baisse dans les cellules tumorales défectueuses de PBRM1. L'expression exogène de l'enzyme de résolution des boucles R, la RNase H1, a inversé la sensibilité des cellules PBRM1 déficientes aux inhibiteurs de la PARP, ce qui suggère que des niveaux excessifs de boucles R pourraient être une cause de cette létalité synthétique. Les inhibiteurs de PARP et d'ATR ont également induit une signalisation immunitaire innée de type GMP cyclique-AMP synthase/stimulateur des gènes de l'interféron (cGAS/STING) dans les cellules tumorales déficientes en PBRM1. Dans l'ensemble, ces résultats fournissent une base préclinique pour l'utilisation des inhibiteurs de PARP dans les cancers déficients en PBRM1. SIGNIFICATION : Cette étude démontre que les inhibiteurs de PARP et d'ATR sont synthétiquement létaux en cas de perte de PBRM1, une sous-unité spécifique du PBAF, ce qui justifie l'évaluation de ces inhibiteurs chez les patients atteints d'un cancer déficient en PBRM1

Utilization of mechanical power and associations with clinical outcomes in brain injured patients: a secondary analysis of the extubation strategies in neuro-intensive care unit patients and associations with outcome (ENIO) trial

Background: There is insufficient evidence to guide ventilatory targets in acute brain injury (ABI). Recent studies have shown associations between mechanical power (MP) and mortality in critical care populations. We aimed to describe MP in ventilated patients with ABI, and evaluate associations between MP and clinical outcomes. Methods: In this preplanned, secondary analysis of a prospective, multi-center, observational cohort study (ENIO, NCT03400904), we included adult patients with ABI (Glasgow Coma Scale ≤ 12 before intubation) who required mechanical ventilation (MV) ≥ 24 h. Using multivariable log binomial regressions, we separately assessed associations between MP on hospital day (HD)1, HD3, HD7 and clinical outcomes: hospital mortality, need for reintubation, tracheostomy placement, and development of acute respiratory distress syndrome (ARDS). Results: We included 1217 patients (mean age 51.2 years [SD 18.1], 66% male, mean body mass index [BMI] 26.3 [SD 5.18]) hospitalized at 62 intensive care units in 18 countries. Hospital mortality was 11% (n = 139), 44% (n = 536) were extubated by HD7 of which 20% (107/536) required reintubation, 28% (n = 340) underwent tracheostomy placement, and 9% (n = 114) developed ARDS. The median MP on HD1, HD3, and HD7 was 11.9 J/min [IQR 9.2–15.1], 13 J/min [IQR 10–17], and 14 J/min [IQR 11–20], respectively. MP was overall higher in patients with ARDS, especially those with higher ARDS severity. After controlling for same-day pressure of arterial oxygen/fraction of inspired oxygen (P/F ratio), BMI, and neurological severity, MP at HD1, HD3, and HD7 was independently associated with hospital mortality, reintubation and tracheostomy placement. The adjusted relative risk (aRR) was greater at higher MP, and strongest for: mortality on HD1 (compared to the HD1 median MP 11.9 J/min, aRR at 17 J/min was 1.22, 95% CI 1.14–1.30) and HD3 (1.38, 95% CI 1.23–1.53), reintubation on HD1 (1.64; 95% CI 1.57–1.72), and tracheostomy on HD7 (1.53; 95%CI 1.18–1.99). MP was associated with the development of moderate-severe ARDS on HD1 (2.07; 95% CI 1.56–2.78) and HD3 (1.76; 95% CI 1.41–2.22). Conclusions: Exposure to high MP during the first week of MV is associated with poor clinical outcomes in ABI, independent of P/F ratio and neurological severity. Potential benefits of optimizing ventilator settings to limit MP warrant further investigation

Extubation in neurocritical care patients: the ENIO international prospective study

Purpose: Neurocritical care patients receive prolonged invasive mechanical ventilation (IMV), but there is poor specific information in this high-risk population about the liberation strategies of invasive mechanical ventilation. Methods: ENIO (NCT03400904) is an international, prospective observational study, in 73 intensive care units (ICUs) in 18 countries from 2018 to 2020. Neurocritical care patients with a Glasgow Coma Score (GCS) ≤ 12, receiving IMV ≥ 24 h, undergoing extubation attempt or tracheostomy were included. The primary endpoint was extubation failure by day 5. An extubation success prediction score was created, with 2/3 of patients randomly allocated to the training cohort and 1/3 to the validation cohort. Secondary endpoints were the duration of IMV and in-ICU mortality. Results: 1512 patients were included. Among the 1193 (78.9%) patients who underwent an extubation attempt, 231 (19.4%) failures were recorded. The score for successful extubation prediction retained 20 variables as independent predictors. The area under the curve (AUC) in the training cohort was 0.79 95% confidence interval (CI95) [0.71-0.87] and 0.71 CI95 [0.61-0.81] in the validation cohort. Patients with extubation failure displayed a longer IMV duration (14 [7-21] vs 6 [3-11] days) and a higher in-ICU mortality rate (8.7% vs 2.4%). Three hundred and nineteen (21.1%) patients underwent tracheostomy without extubation attempt. Patients with direct tracheostomy displayed a longer duration of IMV and higher in-ICU mortality than patients with an extubation attempt (success and failure). Conclusions: In neurocritical care patients, extubation failure is high and is associated with unfavourable outcomes. A score could predict extubation success in multiple settings. However, it will be mandatory to validate our findings in another prospective independent cohort