The efficacy of convalescent plasma for coronavirus disease 2019 (COVID-19) is unclear. Although most randomized controlled trials have shown negative results, uncontrolled studies have suggested that the antibody content could influence patient outcomes. We conducted an open-label, randomized controlled trial of convalescent plasma for adults with COVID-19 receiving oxygen within 12 d of respiratory symptom onset (NCT04348656). Patients were allocated 2:1 to 500 ml of convalescent plasma or standard of care. The composite primary outcome was intubation or death by 30 d. Exploratory analyses of the effect of convalescent plasma antibodies on the primary outcome was assessed by logistic regression. The trial was terminated at 78% of planned enrollment after meeting stopping criteria for futility. In total, 940 patients were randomized, and 921 patients were included in the intention-to-treat analysis. Intubation or death occurred in 199/614 (32.4%) patients in the convalescent plasma arm and 86/307 (28.0%) patients in the standard of care arm—relative risk (RR) = 1.16 (95% confidence interval (CI) 0.94–1.43, P = 0.18). Patients in the convalescent plasma arm had more serious adverse events (33.4% versus 26.4%; RR = 1.27, 95% CI 1.02–1.57, P = 0.034). The antibody content significantly modulated the therapeutic effect of convalescent plasma. In multivariate analysis, each standardized log increase in neutralization or antibody-dependent cellular cytotoxicity independently reduced the potential harmful effect of plasma (odds ratio (OR) = 0.74, 95% CI 0.57–0.95 and OR = 0.66, 95% CI 0.50–0.87, respectively), whereas IgG against the full transmembrane spike protein increased it (OR = 1.53, 95% CI 1.14–2.05). Convalescent plasma did not reduce the risk of intubation or death at 30 d in hospitalized patients with COVID-19. Transfusion of convalescent plasma with unfavorable antibody profiles could be associated with worse clinical outcomes compared to standard care.
The objective of this study was to develop an in vitro cartilage degradation model that emulates the damage seen in early-stage osteoarthritis. To this end, cartilage explants were collagenase-treated to induce enzymatic degradation of collagen fibers and proteoglycans at the articular surface. To assess changes in mechanical properties, intact and degraded cartilage explants were subjected to a series of confined compression creep tests. Changes in extracellular matrix structure and composition were determined using biochemical and histological approaches. Our results show that collagenase-induced degradation increased the amount of deformation experienced by the cartilage explants under compression. An increase in apparent permeability as well as a decrease in instantaneous and aggregate moduli were measured following collagenase treatment. Histological analysis of degraded explants revealed the presence of surface fibrillation, proteoglycan depletion in the superficial and intermediate zones and loss of the lamina splendens. Collagen cleavage was confirmed by the Col II–¾Cshort antibody. Degraded specimens experienced a significant decrease in proteoglycan content but maintained total collagen content. Repetitive testing of degraded samples resulted in the gradual collapse of the articular surface and the compaction of the superficial zone. Taken together, our data demonstrates that enzymatic degradation with collagenase can be used to emulate changes seen in early-stage osteoarthritis. Further, our in vitro model provides information on cartilage mechanics and insights on how matrix changes can affect cartilage’s functional properties. More importantly, our model can be applied to develop and test treatment options for tissue repair.
We have utilized the resonant x-ray diffraction technique at the Mn L-edge in order to directly compare magnetic and orbital correlations in the Mn sub-lattice of Pr0.6Ca0.4MnO3. The resonant line shape is measured below TOO ∼ 240 K at the orbital ordering wave vector (0, ,0,0). Comparing the width of the super-lattice peaks at the two wavevectors, we find that the correlation length of the magnetism exceeds that of the orbital order by nearly a factor of two. Furthermore, we observe a large (∼ 3 eV) shift in spectral weight between the magnetic and orbital line shapes, which cannot be explained within the classic Goodenough picture of a charge-ordered ground state. To explain the large shift, we calculate the resonant line shapes for orbital and magnetic diffraction based on a relaxed charge-ordered model.In a number of manganites, including Pr 1−x Ca x MnO 3 , La 1−x Ca x MnO 3 and La 2−x Sr x MnO 4 , the dynamics resulting in a charge-ordered, insulating state in the vicinity of half-doping are still not well understood. In his seminal work on exchange interactions in manganites, Goodenough considered charge and orbital order at halfdoping as a precursor to the magnetic CE ground state [1]. In this picture, charge ordering at T CO results in a checkerboard pattern of Mn 3+ and Mn 4+ sites (Figure 1). The Mn 3+ sites each have one e g electron and are thus Jahn-Teller (JT) active, while the e g levels are empty on the Mn 4+ sites. A cooperative JT distortion and orbital ordering of the Mn 3+ sites at T OO = T CO occurs concomitantly with the charge ordering. The in-plane JT distortions favor occupation of 3x 2 -r 2 and 3y 2 -r 2
The subtle interplay among electronic degrees of freedom (charge and orbital orderings), spin and lattice distortion that conspire at the Verwey transition in magnetite (Fe3O4) is still a matter of controversy. Here, we provide compelling evidence that these electronic orderings are manifested as a continuous phase transition at the temperature where a spin reorientation takes place at around 130 K, i.e., well above TV approximately 121 K. The Verwey transition seems to leave the orbital ordering unaffected whereas the charge ordering development appears to be quenched at this temperature and the temperature dependence below TV is controlled by the lattice distortions. Finally, we show that the orbital ordering does not reach true long range (disorder), and the correlation length along the c-direction is limited to 100 angstroms.
We report a resonant x-ray diffraction study of the magnetoresistant perovskite Pr0.6Ca0.4MnO3. We discuss the spectra measured above and below the semiconductor-insulator transition temperature with aid of a detailed formal analysis of the energy and polarization dependences of the structure factors and ab initio calculations of the spectra. In the low temperature insulating phase, we find that inequivalent Mn atoms order in a CE-type pattern and that the crystallographic structure of La0.5Ca0.5MnO3, (Radaelli et al., Phys. Rev. B 55, 3015 (1997)) can also describe this system in fine details. Instead, the alternative structure proposed for the so-called Zener polaron model (Daoud-Aladine et al., Phys. Rev. Lett. 89, 097205 (2002)) is ruled out by crystallographic and spectroscopic evidences. Our analysis supports a model involving orbital ordering. However, we confirm that there is no direct evidence of charge disproportionation in the Mn K-edge resonant spectra. Therefore, we consider a CE-type model in which there are two Mn sublattices, each with partial eg occupancy. One sublattice consists of Mn atoms with the 3x 2 − r 2 or 3y 2 − r 2 orbitals partially occupied in a alternating pattern, the other sublattice with the x 2 − y 2 orbital partially occupied.
Using soft-x-ray resonant magnetic scattering in combination with first-principles calculations for noncollinear magnetic configurations we present a new model of the magnetism in ultrathin fcc Fe films on Cu(001). We find the presence of blocks with robust magnetic structure, while the relative directions of the moments of different blocks are sensitive to the detailed atomic structure and temperature. The magnetic noncollinearity is directly demonstrated, which has not been possible so far.
We report the observation of temperature dependent electronic excitations in various manganites utilizing resonant inelastic x-ray scattering (RIXS) at the Mn K-edge. Excitations were observed between 1.5 and 16 eV with temperature dependence found as high as 10 eV. The change in spectral weight between 1.5 and 5 eV was found to be related to the magnetic order and independent of the conductivity. On the basis of LDA+U and Wannier function calculations, this dependence is associated with intersite d-d excitations. Finally, the connection between the RIXS cross-section and the loss function is addressed. PACS numbers: 75.47.Lx, 74.25.Jb, 71.27.+a Manganites of the form RE 1−x AE x MnO 3 where RE is a trivalent rare earth and AE a divalent alkali earth, exhibit a diverse range of magnetic and electronic phases. The recent theoretical and experimental studies have focussed on identifying the electronic ground states and the potential role of phase inhomogeneities [1,2]. However, details of the origin and nature of the electronic order remain elusive. What is known is that the various phases are stabilized through cooperative and competing interactions involving the spin, orbital, charge and electron-lattice degrees of freedom of the states derived from the Mn 3d and the O 2p bands.Current models frequently integrate out the oxygen degrees of freedom and parameterize the behavior of the Mn 3d orbitals with terms such as the hopping amplitude between neighboring Mn sites, the on-site Coulomb repulsion (U ) and the Hund's coupling (J H ), each of which are on the order of several eV. Experimental measurements of the excitation spectra up to these energies can thus play a key role in the understanding of these systems -in particular such measurements provide far more stringent tests of the various theoretical approaches than do ground state measurements. Central to such efforts will be understanding how the excitation spectrum relates to the various magnetic and electronic orderings.In this paper, we report resonant inelastic x-ray scattering studies of the electronic excitation spectrum in a number of manganites, for a range of ground states. We find that in all samples, the excitation spectra show systematic temperature dependencies associated with the magnetic ordering at energy scales up to 10 eV. The integrated spectral weight in the 1 eV to 5 eV energy range increases on entering ferromagnetic phases, decreases for antiferromagnetic spin alignment, and is unchanged through metal-insulator transitions for which the magnetic ground state is unchanged. On the basis of time-dependent density functional calculations, we argue that this temperature dependence arises from intersite d-d excitations which are suppressed or enhanced for antiferromagnetic or ferromagnetic nearest-neighbor spin correlations, respectively. These results both point to the sensitivity of RIXS to magnetic order and to the need for realistic calculations of the q-dependent dielectric function.Inelastic x-ray scattering (IXS), like optical meas...
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