HLA-A*31:01 was reported to be associated with carbamazepine (CBZ)-induced severe cutaneous adverse reactions (SCAR), including drug reaction with eosinophilia and systemic symptoms (DRESS), Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). We conducted an international study using consensus diagnosis criteria to enroll a total of 93 patients with CBZ-SCAR from Europe or Asia. We found that HLA-A*31:01 showed a significant association with CBZ-DRESS in Europeans (P<0.001; odds ratio (OR) (95% confidence interval (CI))=57.6 (11.0-340)), and the strong association was also found in Chinese (P<0.001; OR (95% CI)=23.0 (4.2-125)). However, HLA-A*31:01 had no association with CBZ-SJS/TEN in neither Chinese nor Europeans. By comparison, HLA-B*15:02 showed a strong association with CBZ-SJS/TEN in Chinese (P<0.001, OR (95% CI)=58.1 (17.6-192)). A meta-analysis of this and other published studies confirmed that in all populations, HLA-A*31:01 had an extremely strong association with CBZ-DRESS (P<0.001, a pooled OR (95% CI)=13.2 (8.4-20.8)), but a much weaker association with CBZ-SJS/TEN (P=0.01, OR (95% CI)=3.94 (1.4-11.5)). Our data revealed that HLA-A*31:01 is a specific predictor for CBZ-DRESS but not for CBZ-SJS/TEN. More studies are needed to investigate the genetic determinant of CBZ-SJS/TEN in Europeans. Considering the potential clinical utility, the cost-effectiveness of the combined HLA-A*31:01 and HLA-B*15:02 genetic test to prevent CBZ-SCAR in Chinese needs further investigation.
The Hubbard Model with nearest-neighbor hopping and one type of orbital is applied to small clusters, with emphasis on an octahedron (six sites}. The complete eigenvalue spectrum is calculated. A rather complicated dependence of the spin of the ground state on occupation number, geometry, and model parameters is found. Thermodynamic properties are computed with use of a canonical ensemble. Results are reported for the specific heat, spin susceptibility, and spin-spin correlation functions.
We use the lattice Anderson model on a small cluster to calculate the effect of an external magnetic field on the specific heat of a heavy-fermion system. The suppression of the specific heat results from the spreading of a manifold that contains states of different spins through the Zeeman effect. Our results are compared qualitatively with experiments on CeCu6.A defining characteristic of heavy-fermion metals is the extraordinarily large size of the electronic specific heat at low temperatures.If one writes, in a standard way, C, -yT, then the specific-heat coefficient y can be as large as 2 J/mol (deg) . Additionally, it is sometimes found that specific heat can be drastically reduced by an external magnetic field at very 1ow temperatures and enhanced at slightly larger temperatures. ' We will show here that this behavior can be reproduced in a simple calculation for a finite cluster, although the simplicity of the cluster model does not permit quantitative comparison with experiment. This problem has been discussed from a single-particle viewpoint by Schotte and Schotte and Edelstein in terms of an enhanced density of states around the Fermi energy. Because we consider a small system, we can work with many-body states. Our calculation is essentially exact for a given model cluster, the only caveat being that we ignore the effect of a field on the single-particle hopping.The physical picture which emerges from our calculations is simple. The system is characterized at low energies by a narrow, dense manifold of states which are mostly spin rearrangements of the f electrons. These states are responsible for the high specific heat. We believe this is also true for large (bulk) systems, whether or not the material is ordered magnetically. Although the ground state is a singlet, the manifold contains states with differing values of the total spin quantum number. Application of a magnetic field separates the Zeeman components and broadens the energy distribution.The specific heat will be decreased at some temperatures, generally the lowest, and increased at higher temperature.For temperatures large compared to the width of the manifold, the entropy and specific heat are unaffected by the field.The model is one we have considered previously: a four-site Anderson lattice, with two nondegenerate orbitals (c and f) on each site. The four sites are arranged to form a tetrahedron. We believe this geometry is more appropriate for application to three-dimensional systems than other simple four-site arrangements such as the square or rhombus. Crystal fields and spin-orbit coupling are ignored. These restrictions, which are necessary for our computations, inhibit us from trying to fit experiment data numerically.We are content to demonstrate hereThe last term describes the interaction with an external magnetic field. Let S, = gS;, , r 0.0014r r L / r r r r / I r / r I r / I r r r / r r r 0.0012--3.P t r 0.0010 -,' ; r' rN 'i~/ r r %
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