The cornerstone of life-saving therapy in immune mediated thrombotic thrombocytopenic purpura (iTTP) has been plasma exchange (PEX) combined with immunomodulatory strategies. Caplacizumab, a novel anti-von Willebrand factor nanobody, trialled in two multicentre, randomised-placebo-controlled trials leading to EU and FDA approval, has been available in the UK through a patient-access scheme. Data was collected retrospectively from 2018-2020 for 85 patients receiving caplacizumab, including 4 children, from 22 UK hospitals. Patient characteristics and outcomes in the real-world clinical setting were compared with caplacizumab trial endpoints and historical outcomes in the pre-caplacizumab era. 84/85 patients received steroid and rituximab alongside PEX; 26% required intubation. Median time to platelet count normalisation (3 days), duration of PEX (7 days) and hospital stay (12 days) was comparable with RCT data. Median duration of PEX and time from PEX initiation to platelet count normalisation was favourable compared with historical outcomes (p<0.05). TTP recurrence occurred in 5/85 patients; all with persistent ADAMTS13 activity <5iu/dL. Of 31 adverse events in 26 patients, 17/31 (55%) were bleeding episodes and 5/31 (16%) were thrombotic events (two unrelated to caplacizumab); mortality was 6% (5/85), with no deaths attributed to caplacizumab. In 4/5 deaths caplacizumab was introduced >48 hours after PEX initiation (3-21 days). This real-world evidence represents the first and largest series of TTP patients receiving caplacizumab outside clinical trials, including paediatric patients. Representative of true clinical practice, the findings provide valuable information for clinicians treating TTP globally.
The low energy spin excitation spectrum of the breathing pyrochlore Ba 3 Yb 2 Zn 5 O 11 has been investigated with inelastic neutron scattering. Several nearly resolution limited modes with no observable dispersion are observed at 250 mK while, at elevated temperatures, transitions between excited levels become visible. To gain deeper insight, a theoretical model of isolated Yb 3+ tetrahedra parametrized by four anisotropic exchange constants is constructed. The model reproduces the inelastic neutron scattering data, specific heat, and magnetic susceptibility with high fidelity. The fitted exchange parameters reveal a Heisenberg antiferromagnet with a very large Dzyaloshinskii-Moriya interaction. Using this model, we predict the appearance of an unusual octupolar paramagnet at low temperatures and speculate on the development of inter-tetrahedron correlations.Frustrated or competing interactions have been repeatedly found to be at the root of many unusual phenomena in condensed matter physics [1][2][3][4][5]. By destabilizing conventional long-range order down to low temperature, frustration in magnetic systems can lead to many exotic phases; from unconventional multipolar [6,7] and valence bond solid orders [1,4] to disordered phases such as classical and quantum spin liquids [1,4]. Significant attention has been devoted to understanding geometric frustration where it is the connectivity of the lattice that hinders the formation of order. Recently, however, magnets frustrated not by geometry but by competing interactions have become prominent for the novel behaviors that they host. Such competing interactions might be additional isotropic exchange acting beyond nearest neighbors [8-10], biquadratic or other multipolar interactions [11]. One possibility attracting ever increasing interest is that competing strongly anisotropic interactions may stabilize a wide range of unusual phenomena.An exciting research direction in the latter context concerns itself with so-called "quantum spin ice" [12]. This quantum spin liquid can be stabilized by perturbing classical spin ice with additional anisotropic transverse exchange interactions that induce quantum fluctuations. Particularly interesting is the potential realization of such physics in the rare-earth pyrochlores R 2 M 2 O 7 [13][14][15], where R is a trivalent 4 f rare-earth ion, and M is a non-magnetic tetravalent transition metal ion, such as M=Ti, Sn or Zr. These materials can be described in terms of pseudo spin-1/2 degrees of freedom interacting via anisotropic exchanges [12,15], where the effective spin-1/2 maps the states of the crystal-electric field ground doublet of the rare-earth ion. These materials display a wealth of interesting phenomena, from the possibility of quantum [16][17][18] ion is part of a large and small tetrahedron in the breathing pyrochlore lattice.liquids [22,23]. In many of these compounds, the physics is very delicate, showing strong sample to sample variations [24] or sensitivity to very small amounts of disorder [25,26]. Consequen...
Entanglement of spin and orbital degrees of freedom drives the formation of novel quantum and topological physical states. Discovering new spinorbit entangled ground states and emergent phases of matter requires both experimentally probing the relevant energy scales and applying suitable theoretical models. Here we report resonant inelastic x-ray scattering measurements of the transition metal oxides Ca 3 LiOsO 6 and Ba 2 YOsO 6 . We invoke an intermediate coupling approach that incorporates both spin-orbit coupling and electron-electron interactions on an even footing and reveal the ground state of 5d 3 based compounds, which has remained elusive in previously applied models, is a novel spin-orbit entangled J=3/2 electronic ground state. This work reveals the hidden diversity of spin-orbit controlled ground states in 5d systems and introduces a new arena in the search for spin-orbit controlled phases of matter. Main Text:The electronic ground state adopted by an ion is a fundamental determinant of manifested physical properties. Recently, the importance of spin-orbit coupling (SOC) in creating the electronic ground state in 5d-based compounds has come to the fore and arXiv:1610.02375v1 [cond-mat.str-el] systems, and the influence of SOC has now been observed in the macroscopic properties of numerous systems. However, beyond the J eff = 1/2 case such as that found in Sr 2 IrO 4 (3)-which is a single-hole state that applies only to idealised 5d 5 ions in cubic materialsquestions abound concerning the electronic ground states which govern 5d ion interactions.In this context 5d 3 materials present a particularly intriguing puzzle, because octahedral d 3 configurations are expected to be orbitally-quenched S = 3/2 states -in which case SOC enters only as a 3rd order perturbation (4) -yet there is clear experimental evidence that SOC influences the magnetic properties in 5d 3 transition metal oxides (TMOs). This includes the observations of large, SOC-induced spin-gaps in their magnetic excitation spectra (5-7) and x-ray absorption branching ratios which deviate from BR = I L3 /I L2 = 2 (8, 9).Despite this, no description beyond the S = 3/2 state had been established. synchrotron x-ray and neutron diffraction. Figure 1 presents the x-ray energy loss, E, versus incident energy, E i , RIXS spectra of Ca 3 LiOsO 6 at 300 K. Four lines are present at E < 2 eV, which are enhanced at E i = 10.874 keV, whereas the feature at E ≈ 4.5 eV is enhanced at E i = 10.878 keV. This indicates that the E < 2 eV features are intra-t 2g excitations, whereas the higher energy feature is from t 2g to e g excited states, as has been observed in many 5d oxides (7,(18)(19)(20). Subsequent measurements were optimised to probe the t 2g excitations by fixing E i = 10.874 keV.Figure 2 presents the detailed RIXS spectra of Ca 3 LiOsO 6 and Ba 2 YOsO 6 at temperatures of 300 K and 6 K. In each spectrum there are 5 peaks in addition to the elastic line:four peaks with E < 2 eV, labeled a, b, c and d ( Fig. 2c and d) which we associa...
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