; for the CORIMUNO-19 Collaborative Group IMPORTANCE Severe pneumonia with hyperinflammation and elevated interleukin-6 is a common presentation of coronavirus disease 2019 (COVID-19). OBJECTIVE To determine whether tocilizumab (TCZ) improves outcomes of patients hospitalized with moderate-to-severe COVID-19 pneumonia. DESIGN, SETTING, AND PARTICPANTS This cohort-embedded, investigator-initiated, multicenter, open-label, bayesian randomized clinical trial investigating patients with COVID-19 and moderate or severe pneumonia requiring at least 3 L/min of oxygen but without ventilation or admission to the intensive care unit was conducted between March 31, 2020, to April 18, 2020, with follow-up through 28 days. Patients were recruited from 9 university hospitals in France. Analyses were performed on an intention-to-treat basis with no correction for multiplicity for secondary outcomes. INTERVENTIONS Patients were randomly assigned to receive TCZ, 8 mg/kg, intravenously plus usual care on day 1 and on day 3 if clinically indicated (TCZ group) or to receive usual care alone (UC group). Usual care included antibiotic agents, antiviral agents, corticosteroids, vasopressor support, and anticoagulants. MAIN OUTCOMES AND MEASURES Primary outcomes were scores higher than 5 on the World Health Organization 10-point Clinical Progression Scale (WHO-CPS) on day 4 and survival without need of ventilation (including noninvasive ventilation) at day 14. Secondary outcomes were clinical status assessed with the WHO-CPS scores at day 7 and day 14, overall survival, time to discharge, time to oxygen supply independency, biological factors such as C-reactive protein level, and adverse events. RESULTS Of 131 patients, 64 patients were randomly assigned to the TCZ group and 67 to UC group; 1 patient in the TCZ group withdrew consent and was not included in the analysis. Of the 130 patients, 42 were women (32%), and median (interquartile range) age was 64 (57.1-74.3) years. In the TCZ group, 12 patients had a WHO-CPS score greater than 5 at day 4 vs 19 in the UC group (median posterior absolute risk difference [ARD] −9.0%; 90% credible interval [CrI], −21.0 to 3.1), with a posterior probability of negative ARD of 89.0% not achieving the 95% predefined efficacy threshold. At day 14, 12% (95% CI −28% to 4%) fewer patients needed noninvasive ventilation (NIV) or mechanical ventilation (MV) or died in the TCZ group than in the UC group (24% vs 36%, median posterior hazard ratio [HR] 0.58; 90% CrI, 0.33-1.00), with a posterior probability of HR less than 1 of 95.0%, achieving the predefined efficacy threshold. The HR for MV or death was 0.58 (90% CrI, 0.30 to 1.09). At day 28, 7 patients had died in the TCZ group and 8 in the UC group (adjusted HR, 0.92; 95% CI 0.33-2.53). Serious adverse events occurred in 20 (32%) patients in the TCZ group and 29 (43%) in the UC group (P = .21). CONCLUSIONS AND RELEVANCE In this randomized clinical trial of patients with COVID-19 and pneumonia requiring oxygen support but not admitted to the intensive care...

We have studied the effect of growth and design parameters on the performance of Si-doped GaN/AlN multiquantum-well ͑MQW͒ structures for intersubband optoelectronics in the near infrared. The samples under study display infrared absorption in the 1.3-1.9 m wavelength range, originating from the photoexcitation of electrons from the first to the second electronic level in the QWs. A commonly observed feature is the presence of multiple peaks in both intersubband absorption and interband emission spectra, which are attributed to monolayer thickness fluctuations in the quantum wells. These thickness fluctuations are induced by dislocations and eventually by cracks or metal accumulation during growth. The best optical performance is attained in samples synthesized with a moderate Ga excess during the growth of both the GaN QWs and the AlN barriers without growth interruptions. The optical properties are degraded at high growth temperatures ͑Ͼ720°C͒ due to the thermal activation of the AlN etching of GaN. From the point of view of strain, GaN/AlN MQWs evolve rapidly to an equilibrium average lattice parameter, which is independent of the substrate. As a result, we do not observe any significant effect of the underlayers on the optical performance of the MQW structure. The average lattice parameter is different from the expected value from elastic energy minimization, which points out the presence of periodic misfit dislocations in the structure. The structural quality of the samples is independent of Si doping up to 10 20 cm −3 . By contrast, the intersubband absorption spectrum broadens and blueshifts with doping as a result of electron-electron interactions. This behavior is independent of the Si doping location in the structure, either in the QWs or in the barriers. It is found that the magnitude of the intersubband absorption is not directly determined by the Si concentration in the wells. Instead, depending on the Al mole fraction of the cap layer, the internal electric field due to piezoelectric and spontaneous polarization can deplete or induce charge accumulation in the QWs. In fact, this polarization-induced doping can result in a significant and even dominant contribution to the infrared absorption in GaN/AlN MQW structures.

Background Patients with COVID-19 pneumonia have an excess of inflammation and increased concentrations of cytokines including interleukin-1 (IL-1). We aimed to determine whether anakinra, a recombinant human IL-1 receptor antagonist, could improve outcomes in patients in hospital with mild-to-moderate COVID-19 pneumonia.Methods In this multicentre, open-label, Bayesian randomised clinical trial (CORIMUNO-ANA-1), nested within the CORIMUNO-19 cohort, we recruited patients from 16 University hospitals in France with mild-to-moderate COVID-19 pneumonia, severe acute respiratory syndrome coronavirus 2 infection confirmed by real-time RT-PCR, requiring at least 3 L/min of oxygen by mask or nasal cannula but without ventilation assistance, a score of 5 on the WHO Clinical Progression Scale (WHO-CPS), and a C-reactive protein serum concentration of more than 25 mg/L not requiring admission to the intensive care unit at admission to hospital. Eligible patients were randomly assigned (1:1) using a web-based secure centralised system, stratified by centre and blocked with varying block sizes (randomly of size two or four), to either usual care plus anakinra (200 mg twice a day on days 1-3, 100 mg twice on day 4, 100 mg once on day 5) or usual care alone. Usual care was provided at the discretion of the site clinicians. The two coprimary outcomes were the proportion of patients who had died or needed non-invasive or mechanical ventilation by day 4 (ie, a score of >5 on the WHO-CPS) and survival without need for mechanical or non-invasive ventilation (including high-flow oxygen) at day 14. All analyses were done on an intention-to-treat basis. The trial is registered with ClinicalTrials.gov, NCT04341584, and is now closed to accrual. FindingsBetween April 8 and April 26, 2020, we screened 153 patients. The study was stopped early following the recommendation of the data and safety monitoring board, after the recruitment of 116 patients: 59 were assigned to the anakinra group, and 57 were assigned to the usual care group. Two patients in the usual care group withdrew consent and were not analysed. In the analysable population, the median age was 66 years (IQR 59 to 76) and 80 (70%) participants were men. In the anakinra group, 21 (36%) of 59 patients had a WHO-CPS score of more than 5 at day 4 versus 21 (38%) of 55 in the usual care group (median posterior absolute risk difference [ARD] -2•5%, 90% credible interval [CrI] -17•1 to 12•0), with a posterior probability of ARD of less than 0 (ie, anakinra better than usual care) of 61•2%. At day 14, 28 (47%; 95% CI 33 to 59) patients in the anakinra group and 28 (51%; 95% CI 36 to 62) in the usual care group needed ventilation or died, with a posterior probability of any efficacy of anakinra (hazard ratio [HR] being less than 1) of 54•5% (median posterior HR 0•97; 90% CrI 0•62 to 1•52). At day 90, 16 (27%) patients in the anakinra group and 15 (27%) in the usual care group had died. Serious adverse events occurred in 27 (46%) patients in the anakinra group and 21 (38%) in the usu...

The quantum Hall effect provides a universal standard for electrical resistance that is theoretically based on only the Planck constant h and the electron charge e. Currently, this standard is implemented in GaAs/AlGaAs, but graphene's electronic properties have given hope for a more practical device. Here, we demonstrate that the experimental conditions necessary for the operation of devices made of high-quality graphene grown by chemical vapour deposition on silicon carbide can be extended and significantly relaxed compared with those for state-of-the-art GaAs/AlGaAs devices. In particular, the Hall resistance can be accurately quantized to within 1 × 10(-9) over a 10 T wide range of magnetic flux density, down to 3.5 T, at a temperature of up to 10 K or with a current of up to 0.5 mA. This experimental simplification highlights the great potential of graphene in the development of user-friendly and versatile quantum standards that are compatible with broader industrial uses beyond those in national metrology institutes. Furthermore, the measured agreement of the quantized Hall resistance in graphene and GaAs/AlGaAs, with an ultimate uncertainty of 8.2 × 10(-11), supports the universality of the quantum Hall effect. This also provides evidence of the relation of the quantized Hall resistance with h and e, which is crucial for the new Système International d'unités to be based on fixing such fundamental constants of nature.

Replacing GaAs by graphene to realize more practical quantum Hall resistance standards (QHRS), accurate to within 10−9 in relative value, but operating at lower magnetic fields than 10 T, is an ongoing goal in metrology. To date, the required accuracy has been reported, only few times, in graphene grown on SiC by Si sublimation, under higher magnetic fields. Here, we report on a graphene device grown by chemical vapour deposition on SiC, which demonstrates such accuracies of the Hall resistance from 10 T up to 19 T at 1.4 K. This is explained by a quantum Hall effect with low dissipation, resulting from strongly localized bulk states at the magnetic length scale, over a wide magnetic field range. Our results show that graphene-based QHRS can replace their GaAs counterparts by operating in as-convenient cryomagnetic conditions, but over an extended magnetic field range. They rely on a promising hybrid and scalable growth method and a fabrication process achieving low-electron-density devices.

We propose to grow graphene on SiC by a direct carbon feeding through propane flow in a chemical vapor deposition reactor. X-ray photoemission and low energy electron diffraction show that propane allows to grow few-layer graphene (FLG) on 6H-SiC(0001). Surprisingly, FLG grown on (0001) face presents a rotational disorder similar to that observed for FLG obtained by annealing on (000–1) face. Thanks to a reduced growth temperature with respect to the classical SiC annealing method, we have also grown FLG/3C-SiC/Si(111) in a single growth sequence. This opens the way for large-scale production of graphene-based devices on silicon substrate.

The properties of group III-Nitrides (III-N) such as a large direct bandgap, high melting point, and high breakdown voltage make them very attractive for optoelectronic applications. However, conventional epitaxy on SiC and sapphire substrates results in strained and defective films with consequently poor device performance. In this work, by studying the nucleation of GaN on graphene/SiC by MOVPE, we unambiguously demonstrate the possibility of remote van der Waals epitaxy. By choosing the appropriate growth conditions, GaN crystals can grow either in-plane misoriented or fully epitaxial to the substrate. The adhesion forces across the GaN and graphene interface are very weak and the micron-scale nuclei can be easily moved around. The combined use of x-ray diffraction and transmission electron microscopy demonstrate the growth of stress-free and dislocation-free crystals. The high quality of the crystals was further confirmed by photoluminescence measurements. First principles calculations additionally highlighted the importance of the polarity of the underlying substrate. This work lays the first brick towards the synthesis of high quality III-N thin films grown via van der Waals epitaxy.

Graphene growth from a propane flow in a hydrogen environment (propane-hydrogen chemical vapor deposition (CVD)) on SiC differentiates from other growth methods in that it offers the possibility to obtain various graphene structures on the Si-face depending on growth conditions. The different structures include the (6√3 × 6√3)-R30° reconstruction of the graphene/SiC interface, which is commonly observed on the Si-face, but also the rotational disorder which is generally observed on the C-face. In this work, growth mechanisms leading to the formation of the different structures are studied and discussed. For that purpose, we have grown graphene on SiC(0001) (Si-face) using propane-hydrogen CVD at various pressure and temperature and studied these samples extensively by means of low energy electron diffraction and atomic force microscopy. Pressure and temperature conditions leading to the formation of the different structures are identified and plotted in a pressure-temperature diagram. This diagram, together with other characterizations (X-ray photoemission and scanning tunneling microscopy), is the basis of further discussions on the carbon supply mechanisms and on the kinetics effects. The entire work underlines the important role of hydrogen during growth and its effects on the final graphene structure.