Bringing depth to scanning tunnelling microscopy: subsurface vision of buried nano-objects in metals

A method for subsurface visualization and characterization of hidden subsurface nano-structures based on Scanning Tuneling Microscopy/Spectroscopy (STM/STS) has been developed. The nano-objects buried under a metal surface up to several tens of nanometers can be visualized through the metal surface and characterized with STM without destriying the sample. This non-destructive method exploits quantum well (QW) states formed by partial electron confinement between the surface and buried nano-objects. The specificity of STM allows for nano-objects to be singled out and easily accessed. Then, their shape, size and burial depth can be determined by analysing the spatial distribution and oscillatory behavior of the electron density at the surface of the sample. The proof of concept was demonstrated by fabricating argon nanoclusters embedded into a single-crystalline Cu matrix. Taking advantage of the specific electronic band structure Cu and inner electron focusing, we experimentally demonstrated that noble-gas nanoclusters of several nanometers large buried as deep as 80 nm can be detected, characterized and imaged. The ultime depth of this ability is estimated as 110 nm. This approach using QW states paves the way for an enhanced 3D characterization of nanostructures hidden well below a metallic surface.Comment: Submitted in Nanoscale Horizon

Ontogenic Changes in Hematopoietic Hierarchy Determine Pediatric Specificity and Disease Phenotype in Fusion Oncogene-Driven Myeloid Leukemia.

Fusion oncogenes are prevalent in several pediatric cancers, yet little is known about the specific associations between age and phenotype. We observed that fusion oncogenes, such as ETO2-GLIS2, are associated with acute megakaryoblastic or other myeloid leukemia subtypes in an age-dependent manner. Analysis of a novel inducible transgenic mouse model showed that ETO2-GLIS2 expression in fetal hematopoietic stem cells induced rapid megakaryoblastic leukemia whereas expression in adult bone marrow hematopoietic stem cells resulted in a shift toward myeloid transformation with a strikingly delayed in vivo leukemogenic potential. Chromatin accessibility and single-cell transcriptome analyses indicate ontogeny-dependent intrinsic and ETO2-GLIS2-induced differences in the activities of key transcription factors, including ERG, SPI1, GATA1, and CEBPA. Importantly, switching off the fusion oncogene restored terminal differentiation of the leukemic blasts. Together, these data show that aggressiveness and phenotypes in pediatric acute myeloid leukemia result from an ontogeny-related differential susceptibility to transformation by fusion oncogenes. SIGNIFICANCE: This work demonstrates that the clinical phenotype of pediatric acute myeloid leukemia is determined by ontogeny-dependent susceptibility for transformation by oncogenic fusion genes. The phenotype is maintained by potentially reversible alteration of key transcription factors, indicating that targeting of the fusions may overcome the differentiation blockage and revert the leukemic state.See related commentary by Cruz Hernandez and Vyas, p. 1653.This article is highlighted in the In This Issue feature, p. 1631

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/)

Seasonal and diurnal changes in photosynthesis and carbon partitioning in Vitis vinifera leaves in vines with and without fruit

International audienc

[Evolution of the satisfaction of subjects enrolled in clinical studies]

Within the context of a quality initiative for a clinical research unit, participants' opinions relative to participation conditions allows the identification and quantification of certain dysfunctions in the unit or more widely of the site. An initial satisfaction survey of users of the Grenoble Clinical Research Center showed that the management of volunteers by a staff dedicated to, and in an environment adapted to, clinical research protocols is associated with elevated participant satisfaction. Corrective action has been taken relative to points of dissatisfaction. We conducted a second participant survey from June 1st, 2004, to May 31st, 2005, to measure the impact of our corrective actions. Eighty five percent of the persons contacted responded, and 90.4% of completed questionnaires were valid. The global satisfaction level on a scale of ten was 8.53 +/- 1.16 in 2005 (n = 292) versus 8.61 +/- 1.16 in 2004 (n = 144) (Not Significant = NS). Scores for each dimension of care (comprising 1-6 questions each) were not statistically different between the two years. An improvement was noted for the frequency of physician visits, the communication of results, and the explication of aftercare. On the other hand, there was a moderate decline of the satisfaction score relative to concern for personal needs, the swiftness of check in at arrival and the unit's peace and quiet. Globally, the participation of a subject in clinical research in the context of a Clinical Research Center is associated with a high satisfaction score. Nevertheless, the practice of annual satisfaction surveys permits the sensitisation of staff to certain specifics points, and to observe the effect of corrective action. It serves as an important element in the context of a quality initiative

[Evolution of the satisfaction of subjects enrolled in clinical studies]

Within the context of a quality initiative for a clinical research unit, participants' opinions relative to participation conditions allows the identification and quantification of certain dysfunctions in the unit or more widely of the site. An initial satisfaction survey of users of the Grenoble Clinical Research Center showed that the management of volunteers by a staff dedicated to, and in an environment adapted to, clinical research protocols is associated with elevated participant satisfaction. Corrective action has been taken relative to points of dissatisfaction. We conducted a second participant survey from June 1st, 2004, to May 31st, 2005, to measure the impact of our corrective actions. Eighty five percent of the persons contacted responded, and 90.4% of completed questionnaires were valid. The global satisfaction level on a scale of ten was 8.53 +/- 1.16 in 2005 (n = 292) versus 8.61 +/- 1.16 in 2004 (n = 144) (Not Significant = NS). Scores for each dimension of care (comprising 1-6 questions each) were not statistically different between the two years. An improvement was noted for the frequency of physician visits, the communication of results, and the explication of aftercare. On the other hand, there was a moderate decline of the satisfaction score relative to concern for personal needs, the swiftness of check in at arrival and the unit's peace and quiet. Globally, the participation of a subject in clinical research in the context of a Clinical Research Center is associated with a high satisfaction score. Nevertheless, the practice of annual satisfaction surveys permits the sensitisation of staff to certain specifics points, and to observe the effect of corrective action. It serves as an important element in the context of a quality initiative

Évolution de la satisfaction des usagers du CIC de Grenoble

Dans le cadre de la démarche qualité d'une unité de recherche clinique, l'avis des participants quant aux conditions de participation permet de soulever et quantifier certains dysfonctionnements de l'unité ou plus largement du site. Une première enquête de satisfaction des usagers du Centre d'Investigation Clinique (CIC) de Grenoble avait montré que la prise en charge des sujets par du personnel spécifique et dans un lieu adapté, dans le cadre de protocoles de recherche clinique, était associée à une satisfaction élevée des participants. Des mesures correctives avaient été mises en place concernant les points négatifs. Nous avons réalisé une seconde enquête pour les participants inclus entre le 1$^{\text{er}}$ juin 2004 et le 31 mai 2005, afin de mesurer l'impact des mesures mises en œuvre. Quatre-vingt cinq pour cent des personnes contactées ont répondu à notre enquête et 90,4 % de ces questionnaires étaient exploitables. Le score global, côté sur 10, était de 8,53 ±1,16 en 2005 (n = 292) versus 8,61 ± 1,16 en 2004 (n = 144) [Non Significatif = NS]. Les scores calculés pour les différentes dimensions de soin n'étaient pas non plus statistiquement différents entre les deux années. Une amélioration a été notée pour la fréquence des visites des médecins, la communication des résultats et l'explication du suivi médical. Par contre, une baisse modérée du score de satisfaction concernant le souci des besoins personnels, la rapidité de prise en charge à l'arrivée et le calme du service a été mise en évidence. Globalement, la participation d'un sujet à une recherche biomédicale dans le cadre d'un CIC est associée à un taux de satisfaction élevée. Cependant, la pratique d'enquêtes de satisfaction annuelles permet de sensibiliser le personnel sur certains points spécifiques et d'observer l'effet de la mise en œuvre de mesures correctrices. Elle se révèle un élément important dans le cadre d'une démarche qualité

Can we improve transthoracic echocardiography training in non-cardiologist residents? Experience of two training programs in the intensive care unit

International audienceBackgroundTo evaluate the diagnostic performances of two training programs for residents with no prior ultrasound experience to reach competences in extended basic critical care transthoracic echocardiography (CCE) including Doppler capabilities.MethodsThis is a prospective observational study in two intensive care units of teaching hospitals. Group I (five residents) completed a short training program (4-h theory; 3-h practical); group II (six residents) completed a longer training program (6-h theory; 12-h practical). The residents and an expert examined all patients who required a transthoracic echocardiography. Their agreement studied by Cohen’s κ coefficient, concordance coefficient correlation (CCC) and Bland–Altman plots was used as an indicator of program effectiveness.ResultsGroup I performed 136 CCEs (mean/resident 27; range 22–32; 65 in ventilated patients) in 115 patients (62 men; 64 ± 18 years; Simplified Acute Physiologic Score [SAPS] II 37 ± 18). Group II performed 158 CCEs (mean/resident 26; range 21–31; 65 in ventilated patients) in 108 patients (64 men; 58 ± 17 years; SAPS II 42 ± 22). Both groups adequately assessed left ventricular (LV) systolic function (κ 0.75, 95 % confidence interval [CI] 0.64–0.86; κ 0.77, 95 % CI 0.66–0.88, respectively) and pericardial effusion (κ 0.83, 95 % CI 0.67–0.99; κ 0.76, 95 % CI 0.60–0.93, respectively). Group II appraised severe right ventricular dilatation and significant left-sided valve disease with good to very good agreement (κ 0.80, 95 % CI 0.56–0.96; κ 0.79, 95 % CI 0.66–0.93, respectively). Regarding left ventricular ejection fraction, E/A ratio, E/e′ ratio and aortic peak velocity assessed by group II, CCCs were all >0.70 and the bias (mean difference) ±SD on Bland–Altman analysis was 1.3 ± 8.8 %, 0 ± 0.3, 0.4 ± 2.2 and 0.1 ± 0.4 m/s, respectively. Detection of paradoxical septum (κ 0.65, 95 % CI 0.37–0.93), of heterogeneous LV contraction (κ 0.49, 95 % CI 0.33–0.65) and of respiratory variation of the inferior vena cava (κ 0.27, 95 % CI 0.09–0.45), as well as stroke volume measurement (CCC 0.65, 95 % CI 0.54–0.74; bias ± SD −1.4 ± 4.7 cm), was appraised by group II with moderate agreement requiring probably more comprehensive training.ConclusionsAlthough a training program blending 6-h theory and 12-h practical may be adapted to achieve some essential competences, it seems to be insufficiently to perform a complete extended basic critical care transthoracic echocardiography including Doppler capabilities