Genetic and Immune Predictors for Hypersensitivity Syndrome to Antiepileptic Drugs

Hypersensitivity syndrome reactions (HSR) to antiepileptic drugs (AED) are associated with severe clinical cutaneous adverse reactions (SCAR).Our aims are: to assess HSRs to AEDs using the in vitro lymphocyte toxicity assay (LTA) in patients who manifested HSRs clinically, to correlate LTA results with the clinical syndrome, to correlate LTA results with the human leukocyte antigen (HLA) allele B*1502 (HLA-B*1502) positivity in a Han Chinese-Canadian population, and to determine the cytokine network in this population. HSR patients developed fever and cutaneous eruptions in the presence or absence of organ involvement within 8 weeks of exposure to carbamazepine (CBZ), phenytoin (PHY) or lamotrigine (LTG). Control patients received AEDs without presenting HSR. We investigated 10 CBZ-HSR (4 presented with Stevens-Johnson syndrome (SJS)), 24 CBZ-controls, 10 PHY-HSR (4 presented with drug-induced liver injury (DILI)), 24 PHY-controls, 6 LTG-HSR (1 SJS and 1 DILI) and 24 LTG-controls. There were 30 Han Chinese individuals (14 HSR patients and 16 controls) in our cohort. LTA toxicity greater than 12.5%±2.5% was considered positive. Differences among groups were determined by analysis of variance. In addition, we measured cytokine secretion in the patient sera between 1 month and 3 years after the event. All Han Chinese individuals and 30% of Caucasians were genotyped for HLA-B*1502.A perfect correlation (r=0.92) was observed between positive LTA and clinical diagnosis of DILI and SJS/toxic epidermal necrolysis (TEN). HLA-B*1502 positivity in Han Chinese is a predictor of CBZ-HSR and PHY-HSR. HLA-B*1502-negative Han Chinese receiving only CBZ or a combination of CBZ-PHY tolerated the drug(s) clinically, presenting negative CBZ-LTA and PHY-LTA. However, 3 patients presenting negative CBZ-LTA and PHY-LTA, as well as negative HLA-B*1502, showed positive LTG-LTA (38%, 28% and 25%, respectively), implying that they should not be prescribed LTG. Three patients had LTA positive to both PHY and CBZ, and 3 others had LTA positive to both PHY and LTG. Clinically, all six patients presented HSR to both drugs that they tested positive to (cross-reactivity). Patients were grouped based on the clinical presentation of their symptoms as only rash and fever or a triad that characterizes "true" HSR (rash, fever and DILI or SJS/TEN). Levels of pro-inflammatory cytokines were significantly higher in patient sera compared to control sera. More specifically, the highest levels of tumor necrosis factor (TNF)-α was measured in patients presenting "true" HSR, as were the apoptotic markers Fas, caspase 8 activity and M30. We concluded that LTA is sensitive for DILI and SJS/TEN regardless of drug or ethnicity. HSR prediction will prevent AED-induced morbidity. In Han Chinese, HLA-B*1502 positivity is a predictor for CBZ-HSR and PHY-HSR. Its negativity does not predict a negative LTG-HSR. There is cross-reactivity between AEDs. Additionally, T-cell cytokines and chemokines control the pathogenesis of SJS/TEN and DILI, contributing to apoptotic processes in the liver and in the skin

Measuring cosmological bulk flows via the kinematic Sunyaev-Zeldovich effect in the upcoming cosmic microwave background maps

We propose a new method to measure the possible large-scale bulk flows in the Universe from the cosmic microwave background (CMB) maps from the upcoming missions, MAP and Planck. This can be done by studying the statistical properties of the CMB temperature field at many X-ray cluster positions. At each cluster position, the CMB temperature fluctuation will be a combination of the Sunyaev-Zeldovich (SZ) kinematic and thermal components, the cosmological fluctuations and the instrument noise term. When averaged over many such clusters the last three will integrate down, whereas the first one will be dominated by a possible bulk flow component. In particular, we propose to use all-sky X-ray cluster catalogs that should (or could) be available soon from X-ray satellites, and then to evaluate the dipole component of the CMB field at the cluster positions. We show that for the MAP and Planck mission parameters the dominant contributions to the dipole will be from the terms due to the SZ kinematic effect produced by the bulk flow (the signal we seek) and the instrument noise (the noise in our signal). Computing then the expected signal-to-noise ratio for such measurement, we get that at the 95 % confidence level the bulk flows on scales >100h^{-1} Mpc can be probed down to the amplitude of $< 200$ km/sec with the MAP data and down to only 30 km/sec with the Planck mission.Comment: Astrophysical Journal Letters, in pres

Mixed-state twin observables

Twin observables, i.e. opposite subsystem observables A+ and A- that are indistinguishable in measurement in a given mixed or pure state W, are investigated in detail algebraicly and geometrically. It is shown that there is a far-reaching correspondence between the detectable (in W) spectral entities of the two operators. Twin observables are state-dependently quantum-logically equivalent, and direct subsystem measurement of one of them ipso facto gives rise to the indirect (i.e. distant) measurement of the other. Existence of nontrivial twins requires singularity of W. Systems in thermodynamic equilibrium do not admit subsystem twins. These observables may enable one to simplify the matrix representing W.Comment: 13 page

A spin chain model with non-Hermitian interaction: the Ising quantum spin chain in an imaginary field

We investigate a lattice version of the Yang-Lee model which is characterized by a non-Hermitian quantum spin chain Hamiltonian. We propose a new way to implement PT-symmetry on the lattice, which serves to guarantee the reality of the spectrum in certain regions of values of the coupling constants. In that region of unbroken PT-symmetry we construct a Dyson map, a metric operator and find the Hermitian counterpart of the Hamiltonian for small values of the number of sites, both exactly and perturbatively. Besides the standard perturbation theory about the Hermitian part of the Hamiltonian, we also carry out an expansion in the second coupling constant of the model. Our constructions turns out to be unique with the sole assumption that the Dyson map is Hermitian. Finally we compute the magnetization of the chain in the z and x direction

Biological measurement beyond the quantum limit

Quantum noise places a fundamental limit on the per photon sensitivity attainable in optical measurements. This limit is of particular importance in biological measurements, where the optical power must be constrained to avoid damage to the specimen. By using non-classically correlated light, we demonstrated that the quantum limit can be surpassed in biological measurements. Quantum enhanced microrheology was performed within yeast cells by tracking naturally occurring lipid granules with sensitivity 2.4 dB beyond the quantum noise limit. The viscoelastic properties of the cytoplasm could thereby be determined with a 64% improved measurement rate. This demonstration paves the way to apply quantum resources broadly in a biological context

Vibrational Study of 13C-enriched C60 Crystals

The infrared (IR) spectrum of solid C60 exhibits many weak vibrational modes. Symmetry breaking due to 13C isotopes provides a possible route for optically activating IR-silent vibrational modes. Experimental spectra and a semi-empirical theory on natural abundance and 13C-enriched single crystals of C60 are presented. By comparing the experimental results with the theoretical results, we exclude this isotopic activation mechanism from the explanation for weakly active fundamentals in the spectra.Comment: Accepted for Phys. Rev. B, typeset in REVTEX v3.0 in LaTeX. Postscript file including figures is available at http://insti.physics.sunysb.edu/~mmartin/papers/c13twocol2.ps File with figures will be e-mailed by reques

Surface and lightning sources of nitrogen oxides over the United States: Magnitudes, chemical evolution, and outflow

We use observations from two aircraft during the ICARTT campaign over the eastern United States and North Atlantic during summer 2004, interpreted with a global 3-D model of tropospheric chemistry (GEOS-Chem) to test current understanding of regional sources, chemical evolution, and export of NOx. The boundary layer NOx data provide top-down verification of a 50% decrease in power plant and industry NOx emissions over the eastern United States between 1999 and 2004. Observed NOx concentrations at 8–12 km altitude were 0.55 ± 0.36 ppbv, much larger than in previous U.S. aircraft campaigns (ELCHEM, SUCCESS, SONEX) though consistent with data from the NOXAR program aboard commercial aircraft. We show that regional lightning is the dominant source of this upper tropospheric NOx and increases upper tropospheric ozone by 10 ppbv. Simulating ICARTT upper tropospheric NOx observations with GEOS-Chem requires a factor of 4 increase in modeled NOx yield per flash (to 500 mol/ flash). Observed OH concentrations were a factor of 2 lower than can be explained from current photochemical models, for reasons that are unclear. A NOy-CO correlation analysis of the fraction f of North American NOx emissions vented to the free troposphere as NOy (sum of NOx and its oxidation products) shows observed f = 16 ± 10% and modeled f = 14 ± 9%, consistent with previous studies. Export to the lower free troposphere is mostly HNO3 but at higher altitudes is mostly PAN. The model successfully simulates NOy export efficiency and speciation, supporting previous model estimates of a large U.S. anthropogenic contribution to global tropospheric ozone through PAN export