Analgesic effects of a 5-HT3 receptor antagonist in an animal model of complex regional pain syndrome.

OBJECTIVE: Complex regional pain syndrome (CRPS) is caused by injuries from fracture after trauma and orthopaedic surgical procedures in the hind limbs. The symptoms of CRPS include warmth, pain, allodynia, and hyperalgesia. It is known that 5-hydroxytryptamine 3 (5-HT3) receptors contribute to hyperalgesia, but their role has not yet been fully elucidated. This study investigated the mechanism of pain relief when a 5-HT3 receptor antagonist was administered in a CRPS animal model. MATERIALS AND METHODS: To establish a CRPS animal model, 10-week-old Sprague-Dawley rats were used in the experiment. On the fourth week post tibial fracture surgery, we performed the von Frey test to measure mechanical allodynia. After performing behavioural tests, we collected blood and tissue samples after sacrificing the animals. Enzyme-linked immunosorbent assay and western blot were also performed. RESULTS: The experimental tibia fracture model-induced CRPS animals elicited increased 5-HT3 receptor expression, and the 5-HT transporter was decreased in the brain stem after 4 weeks of surgical intervention. Additionally, in CRPS-induced animals, both the concentration of substance P and the level of interleukin 6 were increased peripherally and centrally. Treatment with the 5-HT3 receptor antagonist, ramosetron, exerted an analgesic effect in the paw withdrawal test and was dependent on the attenuation of the 5-HT3 receptor population with inflammatory pain mediators. CONCLUSIONS: These data suggest that treatment with the 5-HT3 receptor antagonist, ramosetron, in experimental CRPS animal models alleviated pain-related behaviours and may be a new therapeutic option or potential therapeutic agent for patients with CRPS.

Survival of itinerant excitations and quantum spin state transitions in YbMgGaO4 with chemical disorder.

A recent focus of quantum spin liquid (QSL) studies is how disorder/randomness in a QSL candidate affects its true magnetic ground state. The ultimate question is whether the QSL survives disorder or the disorder leads to a "spin-liquid-like" state, such as the proposed random-singlet (RS) state. Since disorder is a standard feature of most QSL candidates, this question represents a major challenge for QSL candidates. YbMgGaO4, a triangular lattice antiferromagnet with effective spin-1/2 Yb3+ions, is an ideal system to address this question, since it shows no long-range magnetic ordering with Mg/Ga site disorder. Despite the intensive study, it remains unresolved as to whether YbMgGaO4 is a QSL or in the RS state. Here, through ultralow-temperature thermal conductivity and magnetic torque measurements, plus specific heat and DC magnetization data, we observed a residual κ0/T term and series of quantum spin state transitions in the zero temperature limit for YbMgGaO4. These observations strongly suggest that a QSL state with itinerant excitations and quantum spin fluctuations survives disorder in YbMgGaO4.

Magnetic ordering in the Ising antiferromagnetic pyrochlore Nd2ScNbO7.

The question of structural disorder and its effects on magnetism is relevant to a number of spin liquid candidate materials. Although commonly thought of as a route to spin glass behaviour, here we describe a system in which the structural disorder results in long-range antiferromagnetic order due to local symmetry breaking. Nd2ScNbO7is shown to have a dispersionless gapped excitation observed in other neodymium pyrochlores belowTN= 0.37 K through polarized and inelastic neutron scattering. However the dispersing spin waves are not observed. This excited mode is shown to occur in only 14(2)% of the neodymium ions through spectroscopy and is consistent with total scattering measurements as well as the magnitude of the dynamic moment 0.26(2)µB. The remaining magnetic species order completely into the all-in all-out Ising antiferromagnetic structure. This can be seen as a result of local symmetry breaking due disordered Sc+3and Nb+5ions about theA-site. From this work, it has been established thatB-site disorder restores the dipole-like behaviour of the Nd+3ions compared to the Nd2B2O7parent series.

Dynamical ground state in the XY pyrochlore Yb2GaSbO7.

The magnetic ground state of the pyrochlore Yb2GaSbO7 has remained an enigma for nearly a decade. The persistent spin fluctuations observed by muon spin relaxation measurements at low temperatures have not been adequately explained for this material using existing theories for quantum magnetism. Here we report on the synthesis and characterisation of Yb2GaSbO7 to elucidate the central physics at play. Through DC and AC magnetic susceptibility, heat capacity, and neutron scattering experiments, we observe evidence for a dynamical ground state that makes Yb2GaSbO7 a promising candidate for disorder-induced spin-liquid or spin-singlet behaviour. This state is quite fragile, being tuned to a splayed ferromagnet in a modest magnetic field µ0Hc∼1.5T.

Possible itinerant excitations and quantum spin state transitions in the effective spin-1/2 triangular-lattice antiferromagnet Na2BaCo(PO4)2.

The most fascinating feature of certain two-dimensional (2D) gapless quantum spin liquid (QSL) is that their spinon excitations behave like the fermionic carriers of a paramagnetic metal. The spinon Fermi surface is then expected to produce a linear increase of the thermal conductivity with temperature that should manifest via a residual value (κ0/T) in the zero-temperature limit. However, this linear in T behavior has been reported for very few QSL candidates. Here, we studied the ultralow-temperature thermal conductivity of an effective spin-1/2 triangular QSL candidate Na2BaCo(PO4)2, which has an antiferromagnetic order at very low temperature (TN ~ 148 mK), and observed a finite κ0/T extrapolated from the data above TN. Moreover, while approaching zero temperature, it exhibits series of quantum spin state transitions with applied field along the c axis. These observations indicate that Na2BaCo(PO4)2 possibly behaves as a gapless QSL with itinerant spin excitations above TN and its strong quantum spin fluctuations persist below TN.

Author Correction: The nature of spin excitations in the one-third magnetization plateau phase of Ba3CoSb2O9.

The original version of this Article omitted the following from the Acknowledgements: 'J. Ma's primary affiliation is Shanghai Jiao Tong University.' This has been corrected in both the PDF and HTML versions of the Article.

The nature of spin excitations in the one-third magnetization plateau phase of Ba3CoSb2O9.

Magnetization plateaus in quantum magnets-where bosonic quasiparticles crystallize into emergent spin superlattices-are spectacular yet simple examples of collective quantum phenomena escaping classical description. While magnetization plateaus have been observed in a number of spin-1/2 antiferromagnets, the description of their magnetic excitations remains an open theoretical and experimental challenge. Here, we investigate the dynamical properties of the triangular-lattice spin-1/2 antiferromagnet Ba3CoSb2O9 in its one-third magnetization plateau phase using a combination of nonlinear spin-wave theory and neutron scattering measurements. The agreement between our theoretical treatment and the experimental data demonstrates that magnons behave semiclassically in the plateau in spite of the purely quantum origin of the underlying magnetic structure. This allows for a quantitative determination of Ba3CoSb2O9 exchange parameters. We discuss the implication of our results to the deviations from semiclassical behavior observed in zero-field spin dynamics of the same material and conclude they must have an intrinsic origin.

Field-Driven Quantum Criticality in the Spinel Magnet ZnCr_{2}Se_{4}.

We report detailed dc and ac magnetic susceptibilities, specific heat, and thermal conductivity measurements on the frustrated magnet ZnCr_{2}Se_{4}. At low temperatures, with an increasing magnetic field, this spinel material goes through a series of spin state transitions from the helix spin state to the spiral spin state and then to the fully polarized state. Our results indicate a direct quantum phase transition from the spiral spin state to the fully polarized state. As the system approaches the quantum criticality, we find strong quantum fluctuations of the spins with behaviors such as an unconventional T^{2}-dependent specific heat and temperature-independent mean free path for the thermal transport. We complete the full phase diagram of ZnCr_{2}Se_{4} under the external magnetic field and propose the possibility of frustrated quantum criticality with extended densities of critical modes to account for the unusual low-energy excitations in the vicinity of the criticality. Our results reveal that ZnCr_{2}Se_{4} is a rare example of a 3D magnet exhibiting a field-driven quantum criticality with unconventional properties.

Comparison of reversal with neostigmine of low-dose rocuronium vs. reversal with sugammadex of high-dose rocuronium for a short procedure.

Some short procedures require deep neuromuscular blockade, which needs to be reversed at the end of the procedure. Forty-four patients undergoing elective laryngeal micro-surgery were randomly allocated into two groups: rocuronium 0.45 mg.kg-1 with neostigmine (50 µg.kg-1 with glycopyrrolate 10 µg.kg-1 ) reversal (moderate block group) vs. rocuronium 0.90 mg.kg-1 with sugammadex (4 mg.kg-1 ) reversal (deep block group). The primary outcome was the intubating conditions during laryngoscopy secondary outcomes included recovery of neuromuscular block; conditions for tracheal intubation; satisfaction score as determined by the surgeon; onset of neuromuscular block; and postoperative sore throat. The onset of neuromuscular block was more rapid, and intubation conditions and ease of intra-operative laryngoscopy were more favourable, and the satisfaction score was lower in the moderate block group compared with the deep block group. No difference was found in the incidence of postoperative sore throat. In laryngeal micro-surgery, the use of rocuronium 0.9 mg.kg-1 with sugammadex for reversal was associated with better surgical conditions and a shorter recovery time than rocuronium 0.45 mg.kg-1 with neostigmine.

Canted magnetic ground state of quarter-doped manganites R 0.75Ca0.25MnO3 (R = Y, Tb, Dy, Ho, and Er).

Polycrystalline samples of the quarter-doped manganites R 0.75Ca0.25MnO3 (R = Y, Tb, Dy, Ho, and Er) were studied by x-ray diffraction and AC/DC susceptibility measurements. All five samples are orthorhombic and exhibit similar magnetic properties: enhanced ferromagnetism below T 1 (∼80 K) and a spin glass (SG) state below T SG (∼30 K). With increasing R 3+ ionic size, both T 1 and T SG generally increase. The single crystal neutron diffraction results on Tb0.75Ca0.25MnO3 revealed that the SG state is mainly composed of a short-range ordered version of a novel canted (i.e. noncollinear) antiferromagnetic spin state. Furthermore, calculations based on the double exchange model for quarter-doped manganites reveal that this new magnetic phase provides a transition state between the ferromagnetic state and the theoretically predicted spin-orthogonal stripe phase.

Magnetism and multiferroicity of an isosceles triangular lattice antiferromagnet Sr3NiNb2O9.

Various experimental measurements were performed to complete the phase diagram of a weakly distorted triangular lattice system, Sr3NiNb2O9 with Ni(2+) , spin-1 magnetic ions. This compound possesses an isosceles triangular lattice with two shorter bonds and one longer bond. It shows a two-step magnetic phase transition at [Formula: see text] K and [Formula: see text] K at zero magnetic field, characteristic of an easy-axis anisotropy. In the magnetization curves, a series of magnetic phase transitions was observed such as an up-up-down phase at [Formula: see text] T with 1/3 of the saturation magnetization (M sat) and an oblique phase at [Formula: see text] T with [Formula: see text]/3 M sat. Intriguingly, the magnetic phase transition below T N2 is in tandem with the ferroelectricity, which demonstrates multiferroic behaviors. Moreover, the multiferroic phase persists in all magnetically ordered phases regardless of the spin structure. The comparison between the phase diagrams of Sr3NiNb2O9 and its sister compound with an equilateral triangular lattice antiferromagnet Ba3NiNb2O9 (Hwang et al 2012 Phys. Rev. Lett. 109 257205), illustrates how a small imbalance among exchange interactions change the magnetic ground states of the TLAFs.

Haploidentical HCT using an αß T-cell-depleted graft with targeted αß(+) cells by add-back after a reduced intensity preparative regimen containing low-dose TBI.

Between 2012 and 2015, 42 pediatric patients underwent haploidentical hematopoietic cell transplantation using an αß(+) T-cell-depleted graft with targeted αß cells at 1-5 × 10(5)/kg by add-back; 31 had hematologic malignancy (HM), 8 had non-malignant disease (NM) and 3 had solid tumors. All patients received uniform reduced-intensity conditioning with fludarabine, cyclophosphamide, rabbit anti-thymocyte globulin and low-dose TBI. All 42 patients achieved neutrophil engraftment at a median of 10 days. The cumulative incidences (CIs) of ⩾grade II and ⩾grade III acute GvHD were 31±7.1% (SE) and 12±5.0%, respectively, and 1-year CI of chronic GvHD was 15±5.8%. One patient died of CMV pneumonia, leading to transplant-related mortality (TRM) of 2.6±2.5%. Sixteen patients relapsed and 11 died of disease. At a median follow-up of 19 months (range, 5-43 months), the estimated 2-year event-free survival for NM and HM were 88±11.7 and 50±10.1%, respectively. Our study demonstrated that haploidentical hematopoietic cell transplantation after ex vivo depletion of αß(+) T cells with targeted dose noticeably reduced the graft failure rate and TRM in pediatric patients and could be applied to patients lacking a suitable related or unrelated donor.

Magnetic Ground States of the Rare-Earth Tripod Kagome Lattice Mg_{2}RE_{3}Sb_{3}O_{14} (RE=Gd,Dy,Er).

We present the structural and magnetic properties of a new compound family, Mg_{2}RE_{3}Sb_{3}O_{14} (RE=Gd,Dy,Er), with a hitherto unstudied frustrating lattice, the "tripod kagome" structure. Susceptibility (ac, dc) and specific heat exhibit features that are understood within a simple Luttinger-Tisza-type theory. For RE=Gd, we found long-ranged order (LRO) at 1.65 K, which is consistent with a 120° structure, demonstrating the importance of diople interactions for this 2D Heisenberg system. For RE=Dy, LRO at 0.37 K is related to the "kagome spin ice" physics for a 2D system. This result shows that the tripod kagome structure accelerates the transition to LRO predicted for the related pyrochlore systems. For RE=Er, two transitions, at 80 mK and 2.1 K are observed, suggesting the importance of quantum fluctuations for this putative XY system.

Interplanar coupling-dependent magnetoresistivity in high-purity layered metals.

The magnetic field-induced changes in the conductivity of metals are the subject of intense interest, both for revealing new phenomena and as a valuable tool for determining their Fermi surface. Here we report a hitherto unobserved magnetoresistive effect in ultra-clean layered metals, namely a negative longitudinal magnetoresistance that is capable of overcoming their very pronounced orbital one. This effect is correlated with the interlayer coupling disappearing for fields applied along the so-called Yamaji angles where the interlayer coupling vanishes. Therefore, it is intrinsically associated with the Fermi points in the field-induced quasi-one-dimensional electronic dispersion, implying that it results from the axial anomaly among these Fermi points. In its original formulation, the anomaly is predicted to violate separate number conservation laws for left- and right-handed chiral (for example, Weyl) fermions. Its observation in PdCoO2, PtCoO2 and Sr2RuO4 suggests that the anomaly affects the transport of clean conductors, in particular near the quantum limit.

Optimum dose of neostigmine to reverse shallow neuromuscular blockade with rocuronium and cisatracurium.

We examined the use of neostigmine for reversing shallow (defined as train-of-four ratio of 0.5), cisatracurium- and rocuronium-induced neuromuscular block in 112 patients, by use of 0 µg.kg(-1) , 10 µg.kg(-1) , 20 µg.kg(-1) or 40 µg.kg(-1) dose of neostigmine for reversal. The times from neostigmine administration to train-of-four ratios of 0.7, 0.9 and 1.0 were evaluated. Analysis of variance showed that the duration of action was significantly longer after cisatracurium compared with rocuronium. The time to reach a train-of-four ratio of 1.0 was significantly shorter with neostigmine 40 µg.kg(-1) compared with lower neostigmine doses, and at this dose the time did not differ between cisatracurium and rocuronium. The recovery time from a train-of-four ratio of 0.5-1.0 did not differ between cisatracurium and rocuronium, and was significantly shortened by the administration of neostigmine. We conclude that a neostigmine dose of 40 µg.kg(-1) was the most effective at reducing recovery time after neuromuscular blockade.

Quantum Oscillation Signatures of Pressure-induced Topological Phase Transition in BiTeI.

We report the pressure-induced topological quantum phase transition of BiTeI single crystals using Shubnikov-de Haas oscillations of bulk Fermi surfaces. The sizes of the inner and the outer FSs of the Rashba-split bands exhibit opposite pressure dependence up to P = 3.35 GPa, indicating pressure-tunable Rashba effect. Above a critical pressure P ~ 2 GPa, the Shubnikov-de Haas frequency for the inner Fermi surface increases unusually with pressure, and the Shubnikov-de Haas oscillations for the outer Fermi surface shows an abrupt phase shift. In comparison with band structure calculations, we find that these unusual behaviors originate from the Fermi surface shape change due to pressure-induced band inversion. These results clearly demonstrate that the topological quantum phase transition is intimately tied to the shape of bulk Fermi surfaces enclosing the time-reversal invariant momenta with band inversion.

Refinement of treatment strategies in ex vivo T-cell-depleted haploidentical SCT for pediatric patients.

We evaluated the feasibility of T-cell-depleted haploidentical hematopoietic SCT (HHCT) in pediatric patients. Between July 2008 and January 2013, 28 patients underwent ex vivo T-cell-depleted HHCT; 9 had hematologic malignancy, 18 had nonmalignant hematologic disease, and 1 had refractory neuroblastoma. Twenty-six patients achieved neutrophil engraftment at a median of 11 days (range, 9-15 days). Two patients failed to achieve primary engraftment and five experienced graft rejection after primary engraftment. These seven patients achieved stable engraftment after a second HHCT. The cumulative incidences (CIs) of⩾grade II and⩾grade III acute GVHD were 33.3% and 14.3%, respectively, and the 1-year CI of extensive chronic GVHD was 11.1%. Four patients died of non-relapse-related causes (two of CMV disease, one of encephalopathy and one of autoimmune hemolytic anemia) and one of leukemia relapse. Non-relapse mortality at 100 days, 1 year and 2 years was 0.0%, 10.7% and 14.3%, respectively. At a median follow-up of 32.8 months (range, 17.0-72.5 months), the 2-year OS was 82.1%. OSs for nonmalignant diseases and malignant diseases were 94.4% and 60.0%, respectively (P=0.019). Thus, HHCT is a realistic alternative for patients with malignant or nonmalignant diseases who lack a suitable donor.

Valley-polarized interlayer conduction of anisotropic Dirac fermions in SrMnBi2.

We report the valley-selective interlayer conduction of SrMnBi(2) under in-plane magnetic fields. The c-axis resistivity of SrMnBi(2) shows clear angular magnetoresistance oscillations indicating coherent interlayer conduction. Strong fourfold variation of the coherent peak in the c-axis resistivity reveals that the contribution of each Dirac valley is significantly modulated by the in-plane field orientation. This originates from anisotropic Dirac Fermi surfaces with strong disparity in the momentum-dependent interlayer coupling. Furthermore, we found a signature of broken valley symmetry at high magnetic fields. These findings demonstrate that a quasi-two-dimensional anisotropic Dirac system can host a valley-polarized interlayer current through magnetic valley control.

Monostotic fibrous dysplasia of the proximal femur: natural history and predisposing factors for disease progression.

Monostotic fibrous dysplasia of the proximal femur has a variable clinical course, despite its reported limited tendency to progress. We investigated the natural history and predisposing factors for progression of dysplasia in a group of 76 patients with a mean follow-up of 8.5 years (2.0 to 15.2). Of these, 31 (41%) presented with an asymptomatic incidental lesion while 45 (59%) presented with pain or a pathological fracture. A group of 23 patients (30%) underwent early operative treatment for pain (19: 25%) or pathological fracture (4: 5%). Of the 53 patients who were initially treated non-operatively, 45 (85%) remained asymptomatic but eight (15%) needed surgery because of pain or fracture. The progression-free survival of the observation group was 81% (sd 6.4%) at five-years follow-up. An initial presentation of pain (p < 0.001), a limp (p < 0.001), radiological evidence of microfracture (p = 0.001) and younger age (< 17 years) (p = 0.016) were significant predisposing factors for disease progression. The risk of experiencing pain or pathological fracture is considerable in monostotic fibrous dysplasia of the proximal femur. Patients presenting with pain, a limp or radiological evidence of microfracture have a high chance of needing surgical treatment.

Successful rescue of early graft failure in pediatric patients using T-cell-depleted haploidentical hematopoietic SCT.

Graft failure (GF) is a significant complication after allogeneic hematopoietic stem cell transplantation (HCT) and is associated with a high mortality rate. We performed re-transplantation using haploidentical-related donors to rescue children with early GF. Between 2008 and 2013, 10 patients received re-transplantation from haploidentical family donors. The median age at HCT was 13.5 years and the median time between transplantations was 52.5 days. Conditioning regimen with fludarabine and CY was used in seven patients, and TBI was added in three patients. All 10 patients received T-cell-depleted grafts using CD3 or CD3/CD19 MoAb. The median numbers of CD34(+) and CD3(+) cells were 5.52 × 10(6)/kg and 1.08 × 10(6)/kg, respectively. For GVHD prophylaxis, mycophenolate mofetil (MMF) and tacrolimus or MMF and CYA were used. All 10 patients achieved a sustained neutrophil engraftment and maintained a complete donor chimerism at the time of analysis (median 23 months, range 6-62 months). Nine of 10 patients were alive, and one patient with moyamoya disease with AML died of encephalopathy 7 months post transplant. This study suggests that fludarabine- and CY-based conditioning with T-cell-depleted haploidentical HCT is a feasible option to rescue pediatric patients with primary GF.