Altimetry for the future: Building on 25 years of progress

In 2018 we celebrated 25 years of development of radar altimetry, and the progress achieved by this methodology in the fields of global and coastal oceanography, hydrology, geodesy and cryospheric sciences. Many symbolic major events have celebrated these developments, e.g., in Venice, Italy, the 15th (2006) and 20th (2012) years of progress and more recently, in 2018, in Ponta Delgada, Portugal, 25 Years of Progress in Radar Altimetry. On this latter occasion it was decided to collect contributions of scientists, engineers and managers involved in the worldwide altimetry community to depict the state of altimetry and propose recommendations for the altimetry of the future. This paper summarizes contributions and recommendations that were collected and provides guidance for future mission design, research activities, and sustainable operational radar altimetry data exploitation. Recommendations provided are fundamental for optimizing further scientific and operational advances of oceanographic observations by altimetry, including requirements for spatial and temporal resolution of altimetric measurements, their accuracy and continuity. There are also new challenges and new openings mentioned in the paper that are particularly crucial for observations at higher latitudes, for coastal oceanography, for cryospheric studies and for hydrology. The paper starts with a general introduction followed by a section on Earth System Science including Ocean Dynamics, Sea Level, the Coastal Ocean, Hydrology, the Cryosphere and Polar Oceans and the ‘‘Green” Ocean, extending the frontier from biogeochemistry to marine ecology. Applications are described in a subsequent section, which covers Operational Oceanography, Weather, Hurricane Wave and Wind Forecasting, Climate projection. Instruments’ development and satellite missions’ evolutions are described in a fourth section. A fifth section covers the key observations that altimeters provide and their potential complements, from other Earth observation measurements to in situ data. Section 6 identifies the data and methods and provides some accuracy and resolution requirements for the wet tropospheric correction, the orbit and other geodetic requirements, the Mean Sea Surface, Geoid and Mean Dynamic Topography, Calibration and Validation, data accuracy, data access and handling (including the DUACS system). Section 7 brings a transversal view on scales, integration, artificial intelligence, and capacity building (education and training). Section 8 reviews the programmatic issues followed by a conclusion

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

Altimetry for the future: building on 25 years of progress

In 2018 we celebrated 25 years of development of radar altimetry, and the progress achieved by this methodology in the fields of global and coastal oceanography, hydrology, geodesy and cryospheric sciences. Many symbolic major events have celebrated these developments, e.g., in Venice, Italy, the 15th (2006) and 20th (2012) years of progress and more recently, in 2018, in Ponta Delgada, Portugal, 25 Years of Progress in Radar Altimetry. On this latter occasion it was decided to collect contributions of scientists, engineers and managers involved in the worldwide altimetry community to depict the state of altimetry and propose recommendations for the altimetry of the future. This paper summarizes contributions and recommendations that were collected and provides guidance for future mission design, research activities, and sustainable operational radar altimetry data exploitation. Recommendations provided are fundamental for optimizing further scientific and operational advances of oceanographic observations by altimetry, including requirements for spatial and temporal resolution of altimetric measurements, their accuracy and continuity. There are also new challenges and new openings mentioned in the paper that are particularly crucial for observations at higher latitudes, for coastal oceanography, for cryospheric studies and for hydrology. The paper starts with a general introduction followed by a section on Earth System Science including Ocean Dynamics, Sea Level, the Coastal Ocean, Hydrology, the Cryosphere and Polar Oceans and the “Green” Ocean, extending the frontier from biogeochemistry to marine ecology. Applications are described in a subsequent section, which covers Operational Oceanography, Weather, Hurricane Wave and Wind Forecasting, Climate projection. Instruments’ development and satellite missions’ evolutions are described in a fourth section. A fifth section covers the key observations that altimeters provide and their potential complements, from other Earth observation measurements to in situ data. Section 6 identifies the data and methods and provides some accuracy and resolution requirements for the wet tropospheric correction, the orbit and other geodetic requirements, the Mean Sea Surface, Geoid and Mean Dynamic Topography, Calibration and Validation, data accuracy, data access and handling (including the DUACS system). Section 7 brings a transversal view on scales, integration, artificial intelligence, and capacity building (education and training). Section 8 reviews the programmatic issues followed by a conclusion

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

Fonction des facteurs de transcription Olig1 et Olig2 dans les cellules souches neurales du système nerveux central (Etude d'un modèle de souris transgéniques d'expression inductible)

L'objectif de ma thèse a été de définir l'impact de la sur-expression des facteurs de transcription Olig sur la différenciation des cellules souches neurales en oligodendrocyte dans un modèle de souris transgénique. L'expression des transgènes est induite par la doxycycline dans les cellules souches nestine+. Au cours du développement, l'expression forcée de Olig1 ou Olig2 induit une genèse ectopique d'oligodendrocytes. De plus, la sur-expression de Olig2 bloque la spécification des interneurones V3. En post-natal, la sur-expression de Olig2 dans les zones germinatives provoque une myélinisation précoce et une augmentation du nombre d'astrocytes dans le corps calleux. L'ensemble de mes résultats indique que la sur-expression des facteurs Olig pourrait constituer une stratégie thérapeutique intéressante pour promouvoir la régénération de la myéline dans des pathologies démyélinisantes, telle que la scérose en plaques.Olig1 and Olig2 are b-HLH transcription factors involved in oligodendrocyte development in the central nervous system. My project aims to analyse the effect of Olig gene over-expression in neural stem cells. Therefore, I designed and analyzed transgenic mice models with inducible expression of Olig genes in nestin+ neural stem/progenitor cells (Tet-On system). At embryonic stages, forced expression of Olig1 and Olig2 leads to ectopic expression of oligodendrocyte markers. Moreover, Olig2 over-expression decreased V3 interneuron specification. At postnatal stage Olig2 over-expression in germinative area induced earlier myelination and astrocyte specification in corpus callosum. These transgenic mice provide a useful model to test whether forced expression of Olig genes represents a possible strategy to enhance remyelination in demyelinating disease such as multiple sclerosis.PARIS5-BU Méd.Cochin (751142101) / SudocSudocFranceF

Modèle Numérique pour la Stimulation Ultrasonore in-vitro de Cellules Osseuses : une Etude Paramétrique

Dans le début des années 50, les premières observations cliniques des effets de la Stimulation Ultrasonore pour la Régénération Osseuse [ou Ultrasound Stimulation on Bone Regeneration (USBR)] sont rapportées. En 1994, la FDA (Food and Drug Administration, USA) a autorisé l’utilisation des USBR pour des applications cliniques. Néanmoins, les effets de la mécanotransduction ultrasonore (la capacité de déclencher une réponse biologique en utilisant une stimulation mécanique) sont encore incompris à ce jour et l’utilisation des ultrasons pour la régénération osseuse reste controversée. Afin de mieux comprendre l’interaction entre les ultrasons et les cellules osseuses, le développement d’un dispositif expérimental in-vitro est une étape clé. L’un des premiers défis est de caractériser et de contrôler la dose d’ultrasons délivrée aux cellules à l’intérieur d’une boîte de Petri. Afin d’éviter les phénomènes perturbants, tels que les réflexions multiples ou les ondes stationnaires, un dispositif expérimental innovant incluant un bouchon anti- réflexion, a été proposé. Dans ce dispositif, des cellules osseuses sont ensemencées dans une boîte de Petri (les cellules recouvrent une surface de 35 mm de diamètre) et sont stimulées par un transducteur à 1 MHz (qui mesure 13 mm de diamètre). Les résultats expérimentaux montrent que le maximum de l’intensité est concentré au milieu de la boîte de Petri. Cela signifie que les cellules, une fois ensemencées dans la boîte, ne seront pas stimulées par la même intensité acoustique. Afin d’élargir et d’homogénéiser la distribution de l’intensité acoustique à l’intérieur de la boîte de Petri, une lentille acoustique est conçue. Dans cette étude, un modèle numérique utilisant la méthode des éléments finis et reproduisant le dispositif expérimental, est développé sous Comsol Multiphysics®. Différentes études paramétriques sont réalisées afin de déterminer la taille de la lentille, sa composition, la distance entre le transducteur et le boîte de Petri, et la fréquence d’excitation nominale

Caractérisation Ultrasonore du Délai Post-Mortem d'Os Humains

International audienceAfin d’améliorer l’évaluation du délai post-mortem (DPM) de l’os humain, les experts en anthropologie judiciaire de la gendarmerie nationale s’intéressent à de nouvelles méthodes et notamment au contrôle non destructif (CND). Si les méthodes de colorimétrie par Bleu du Nil permettent actuellement une datation jusqu’à cent ans, ces techniques altèrent l’os qui est une pièce à conviction dans une enquête criminelle. Afin d’éviter cette dégradation, le travail présenté ici propose une méthode de caractérisation du DPM par des méthodes ultrasonores ayant fait leur preuve pour le CND de matériaux complexes, y compris des os dans les applications médicales. L’objectif est d’identifier les paramètres ultrasonores pertinents représentatifs de l’âge post-mortem. Les vitesses de propagation des ondes de compression et de cisaillement sont mesurées à travers des échantillons parallélépipédiques d’os cortical prélevés sur des fémurs humains en respectant l’orientation anatomique de l’os. Ces mesures effectuées dans les 3 directions de l’espace permettent de calculer les coefficients diagonaux de la matrice de rigidité. Les mesures de vitesse de propagation des ondes de compression sont effectuées en transmission, à l’aide de PinducersTM émetteur / récepteur en immersion dans l’eau. La mesure des vitesses des ondes de cisaillement est faite via un second dispositif non immergé utilisant des transducteurs de contact. Les résultats présentés sont issus des signatures ultrasonores mesurées sur des os, provenant d’individus aux paramètres pré-mortem similaires, dont le DPM varie entre 1 et 50 ans. Les six coefficients diagonaux de la matrice de rigidité sont représentés et discutés en fonction du DPM. Une première classification des os est possible selon leur âge post-mortem. Afin de faciliter la lecture et l’interprétation des résultats, un paramètre unique est proposé, la trace de matrice de rigidité, confirmant la contribution possible de la technique ultrasonore employée pour la datation des os humains

Acoustic intensity monitoring in a 2D cell culture under low intensity ultrasound stimulation

International audienc