Atomically thin two-dimensional (2D) metals may be key ingredients in next-generation quantum and optoelectronic devices. However, 2D metals must be stabilized against environmental degradation and ...integrated into heterostructure devices at the wafer scale. The high-energy interface between silicon carbide and epitaxial graphene provides an intriguing framework for stabilizing a diverse range of 2D metals. Here we demonstrate large-area, environmentally stable, single-crystal 2D gallium, indium and tin that are stabilized at the interface of epitaxial graphene and silicon carbide. The 2D metals are covalently bonded to SiC below but present a non-bonded interface to the graphene overlayer; that is, they are 'half van der Waals' metals with strong internal gradients in bonding character. These non-centrosymmetric 2D metals offer compelling opportunities for superconducting devices, topological phenomena and advanced optoelectronic properties. For example, the reported 2D Ga is a superconductor that combines six strongly coupled Ga-derived electron pockets with a large nearly free-electron Fermi surface that closely approaches the Dirac points of the graphene overlayer.
Near-infrared-to-visible second harmonic generation from air-stable two-dimensional polar gallium and indium metals is described. The photonic properties of 2D metals - including the largest ...second-order susceptibilities reported for metals (approaching 10nm\(^2\)/V) - are determined by the atomic-level structure and bonding of two-to-three-atom-thick crystalline films. The bond character evolved from covalent to metallic over a few atomic layers, changing the out-of-plane metal-metal bond distances by approximately ten percent (0.2 \(\unicode{x212B}\)), resulting in symmetry breaking and an axial electrostatic dipole that mediated the large nonlinear response. Two different orientations of the crystalline metal atoms, corresponding to lateral displacements < 2 \(\unicode{x212B}\), persisted in separate micron-scale terraces to generate distinct harmonic polarizations. This strong atomic-level structure-property interplay suggests metal photonic properties can be controlled with atomic precision.
Intercalation of atomic species through epitaxial graphene layers began only a few years following its initial report in 2004. The impact of intercalation on the electronic properties of the graphene ...is well known; however, the intercalant itself can also exhibit intriguing properties not found in nature. This suggests that a shift in the focus of epitaxial graphene intercalation studies may lead to fruitful exploration of many new forms of traditionally 3D materials. In the following forward-looking review, we summarize the primary techniques used to achieve and characterize EG intercalation, and introduce a new, facile approach to readily achieve metal intercalation at the graphene/silicon carbide interface. We show that simple thermal evaporation-based methods can effectively replace complicated synthesis techniques to realize large-scale intercalation of non-refractory metals. We also show that these methods can be extended to the formation of compound materials based on intercalation. Two-dimensional (2D) silver (2D-Ag) and large-scale 2D gallium nitride (2D-GaNx) are used to demonstrate these approaches.
Three-dimensional epitaxial heterostructures are based on covalently-bonded interfaces, whereas those from 2-dimensional (2D) materials exhibit van der Waals interactions. Under the right conditions, ...however, material structures with mixed interfacial van der Waals and covalent bonding may be realized. Atomically thin layers formed at the epitaxial graphene (EG)/silicon carbide (SiC) interface indicate that EG/SiC interfaces provide this unique environment and enable synthesis of a rich palette of 2D materials not accessible with traditional techniques. Here, we demonstrate a method termed confinement heteroepitaxy (CHet), to realize air-stable, structurally unique, crystalline 2D-Ga, In, and Sn at the EG/SiC interface. The first intercalant layer is covalently-bonded to the SiC, and is accompanied by a vertical bonding gradient that ends with van der Waals interactions. Such structures break out of plane centrosymmetry, thereby introducing atomically thin, non-centrosymmetric 2D allotropes of 3D materials as a foundation for tunable superconductivity, topological states, and plasmonic properties.
BackgroundThe first wave of the coronavirus disease (COVID-19) pandemic spread rapidly in Spain, one of Europe's most affected countries. A national lockdown was implemented on 15 March 2020.AimTo ...describe reported cases and the impact of national lockdown, and to identify disease severity risk factors.MethodsNational surveillance data were used to describe PCR-confirmed cases as at 27 April 2020. We compared case characteristics by severity categories (hospitalisation, admission to intensive care unit (ICU), death) and identified severity risk factors using multivariable regression.ResultsThe epidemic peaked on 20 March. Of 218,652 COVID-19 cases, 45.4% were hospitalised, 4.6% were admitted to ICU and 11.9% died. Among those who died, 94.8% had at least one underlying disease. Healthcare workers (HCWs) represented 22.9% of cases. Males were more likely to have severe outcomes than females. Cardiovascular disease was a consistent risk factor. Patients with pneumonia had higher odds of hospitalisation (odds ratio (OR): 26.63; 95% confidence interval (CI): 25.03-28.33). The strongest predictor of death was age ≥ 80 years (OR: 28.4; 95% CI: 19.85-40.78). Among underlying diseases, chronic renal disease had highest odds of death (OR: 1.47; 95% CI: 1.29-1.68).ConclusionsCOVID-19 case numbers began declining 6 days after the national lockdown. The first wave of the COVID-19 pandemic in Spain had a severe impact on elderly people. Patients with cardiovascular or renal conditions were at higher risk for severe outcomes. A high proportion of cases were HCWs. Enhanced surveillance and control measures in these subgroups are crucial during future COVID-19 waves.
In late summer 2010 a mosquito born flavivirus not previously reported in Europe called Bagaza virus (BAGV) caused high mortality in red-legged partridges (Alectoris rufa) and ring-necked pheasants ...(Phasianus colchicus). We studied clinical findings, lesions and viral antigen distribution in naturally BAGV infected game birds in order to understand the apparently higher impact on red-legged partridges. The disease induced neurologic signs in the two galliform species and, to a lesser extent, in common wood pigeons (Columba palumbus). In red-legged partridges infection by BAGV caused severe haemosiderosis in the liver and spleen that was absent in pheasants and less evident in common wood pigeons. Also, BAGV antigen was present in vascular endothelium in multiple organs in red-legged partridges, and in the spleen in common wood pigeons, while in ring-necked pheasants it was only detected in neurons and glial cells in the brain. These findings indicate tropism of BAGV for endothelial cells and a severe haemolytic process in red-legged partridges in addition to the central nervous lesions that were found in all three species.
Objective
Design a risk model to predict bacteraemia in patients attended in emergency departments (ED) for an episode of infection.
Methods
This was a national, prospective, multicentre, ...observational cohort study of blood cultures (BC) collected from adult patients (≥ 18 years) attended in 71 Spanish EDs from October 1 2019 to March 31, 2020. Variables with a
p
value < 0.05 were introduced in the univariate analysis together with those of clinical significance. The final selection of variables for the scoring scale was made by logistic regression with selection by introduction. The results obtained were internally validated by dividing the sample in a derivation and a validation cohort.
Results
A total of 4,439 infectious episodes were included. Of these, 899 (20.25%) were considered as true bacteraemia. A predictive model for bacteraemia was defined with seven variables according to the Bacteraemia Prediction Model of the INFURG-SEMES group (MPB-INFURG-SEMES). The model achieved an area under the curve-receiver operating curve of 0.924 (CI 95%:0.914–0.934) in the derivation cohort, and 0.926 (CI 95%: 0.910–0.942) in the validation cohort. Patients were then split into ten risk categories, and had the following rates of risk: 0.2%(0 points), 0.4%(1 point), 0.9%(2 points), 1.8%(3 points), 4.7%(4 points), 19.1% (5 points), 39.1% (6 points), 56.8% (7 points), 71.1% (8 points), 82.7% (9 points) and 90.1% (10 points). Findings were similar in the validation cohort. The cut-off point of five points provided the best precision with a sensitivity of 95.94%, specificity of 76.28%, positive predictive value of 53.63% and negative predictive value of 98.50%.
Conclusion
The MPB-INFURG-SEMES model may be useful for the stratification of risk of bacteraemia in adult patients with infection in EDs, together with clinical judgement and other variables independent of the process and the patient.
Background
CPX‐351 is approved for the treatment of therapy related acute myeloid leukemia (t‐AML) and AML with myelodysplastic related changes (MRC‐AML). The benefits of this treatment over standard ...chemotherapy has not been addressed in well matched cohorts of real‐life patients.
Methods
Retrospective analysis of AML patients treated with CPX‐351 as per routine practice. A propensity score matching (PSM) was used to compare their main outcomes with those observed in a matched cohort among 765 historical patients receiving intensive chemotherapy (IC), all of them reported to the PETHEMA epidemiologic registry.
Results
Median age of 79 patients treated with CPX‐351 was 67 years old (interquartile range 62–71), 53 were MRC‐AML. The complete remission (CR) rate or CR without recovery (CRi) after 1 or 2 cycles of CPX‐351 was 52%, 60‐days mortality 18%, measurable residual disease <0.1% in 54% (12 out of 22) of them. Stem cell transplant (SCT) was performed in 27 patients (34%), median OS was 10.3 months, and 3‐year relapse incidence was 50%. Using PSM, we obtained two comparable cohorts treated with CPX‐351 (n = 52) or IC (n = 99), without significant differences in CR/CRi (60% vs. 54%) and median OS (10.3 months vs. 9.1 months), although more patients were bridged to SCT in the CPX‐351 group (35% vs. 12%). The results were confirmed when only 3 + 7 patients were included in the historical cohort. In multivariable analyses, SCT was associated with better OS (HR 0.33 95% CI: 0.18–0.59), p < 0.001.
Conclusion
Larger post‐authorization studies may provide evidence of the clinical benefits of CPX‐351 for AML in the real‐life setting.
We report the results of CPX‐351 treatment in a group of 79 non‐selected patients reported to the PETHEMA epidemiologic registry and compared the main outcomes with a matched cohort among 765 historical patients receiving intensive chemotherapy. After propensity score matching, no differences in complete remission (60% vs. 54%) and median overall survival (10.3 months vs. 9.1 months) were observed between cohorts, although more patients were bridged to allogeneic transplant in the CPX‐351 group (35% vs. 12%). The results were confirmed when only 3 + 7 treated patients were included in the historical cohort.
Introduction
SARS-CoV-2 pneumonia is often associated with hyper-inflammation. The cytokine-storm-like is one of the targets of current therapies for coronavirus disease 2019 (COVID-19). High ...Interleukin-6 (IL6) blood levels have been identified in severe COVID-19 disease, but there are still uncertainties regarding the actual role of anti-IL6 antagonists in COVID-19 management. Our hypothesis was that the use of sarilumab plus corticosteroids at an early stage of the hyper-inflammatory syndrome would be beneficial and prevent progression to acute respiratory distress syndrome (ARDS).
Methods
We randomly assigned (in a 1:1 ratio) COVID-19 pneumonia hospitalized patients under standard oxygen therapy and laboratory evidence of hyper-inflammation to receive sarilumab plus usual care (experimental group) or usual care alone (control group). Corticosteroids were given to all patients at a 1 mg/kg/day of methylprednisolone for at least 3 days. The primary outcome was the proportion of patients progressing to severe respiratory failure (defined as a score in the Brescia-COVID19 scale ≥ 3) up to day 15.
Results
A total of 201 patients underwent randomization: 99 patients in the sarilumab group and 102 patients in the control group. The rate of patients progressing to severe respiratory failure (Brescia-COVID scale score ≥ 3) up to day 15 was 16.16% in the Sarilumab group versus 15.69% in the control group (RR 1.03; 95% CI 0.48–2.20). No relevant safety issues were identified.
Conclusions
In hospitalized patients with Covid-19 pneumonia, who were under standard oxygen therapy and who presented analytical inflammatory parameters, an early therapeutic intervention with sarilumab plus standard of care (including corticosteroids) was not shown to be more effective than current standard of care alone. The study was registered at EudraCT with number: 2020-002037-15.
Populations of RNA viruses are composed of complex and dynamic mixtures of variant genomes that are termed mutant spectra or mutant clouds. This applies also to SARS-CoV-2, and mutations that are ...detected at low frequency in an infected individual can be dominant (represented in the consensus sequence) in subsequent variants of interest or variants of concern. Here we briefly review the main conclusions of our work on mutant spectrum characterization of hepatitis C virus (HCV) and SARS-CoV-2 at the nucleotide and amino acid levels and address the following two new questions derived from previous results: (i) how is the SARS-CoV-2 mutant and deletion spectrum composition in diagnostic samples, when examined at progressively lower cut-off mutant frequency values in ultra-deep sequencing; (ii) how the frequency distribution of minority amino acid substitutions in SARS-CoV-2 compares with that of HCV sampled also from infected patients. The main conclusions are the following: (i) the number of different mutations found at low frequency in SARS-CoV-2 mutant spectra increases dramatically (50- to 100-fold) as the cut-off frequency for mutation detection is lowered from 0.5% to 0.1%, and (ii) that, contrary to HCV, SARS-CoV-2 mutant spectra exhibit a deficit of intermediate frequency amino acid substitutions. The possible origin and implications of mutant spectrum differences among RNA viruses are discussed.