Rituximab monitoring and redosing in pediatric neuromyelitis optica spectrum disorder.

Abstract OBJECTIVE: To study rituximab in pediatric neuromyelitis optica (NMO)/NMO spectrum disorders (NMOSD) and the relationship between rituximab, B cell repopulation, and relapses in order to improve rituximab monitoring and redosing. METHODS: Multicenter retrospective study of 16 children with NMO/NMOSD receiving 652 rituximab courses. According to CD19 counts, events during rituximab were categorized as "repopulation," "depletion," or "depletion failure" relapses (repopulation threshold CD19 6510 7 10(6) cells/L). RESULTS: The 16 patients (14 girls; mean age 9.6 years, range 1.8-15.3) had a mean of 6.1 events (range 1-11) during a mean follow-up of 6.1 years (range 1.6-13.6) and received a total of 76 rituximab courses (mean 4.7, range 2-9) in 42.6-year cohort treatment. Before rituximab, 62.5% had received azathioprine, mycophenolate mofetil, or cyclophosphamide. Mean time from rituximab to last documented B cell depletion and first repopulation was 4.5 and 6.8 months, respectively, with large interpatient variability. Earliest repopulations occurred with the lowest doses. Significant reduction between pre- and post-rituximab annualized relapse rate (ARR) was observed (p = 0.003). During rituximab, 6 patients were relapse-free, although 21 relapses occurred in 10 patients, including 13 "repopulation," 3 "depletion," and 4 "depletion failure" relapses. Of the 13 "repopulation" relapses, 4 had CD19 10-50 7 10(6) cells/L, 10 had inadequate monitoring ( 641 CD19 in the 4 months before relapses), and 5 had delayed redosing after repopulation detection. CONCLUSION: Rituximab is effective in relapse prevention, but B cell repopulation creates a risk of relapse. Redosing before B cell repopulation could reduce the relapse risk further. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that rituximab significantly reduces ARR in pediatric NMO/NMOSD. This study also demonstrates a relationship between B cell repopulation and relapses

Further studies on relic neutrino asymmetry generation II: a rigorous treatment of repopulation in the adiabatic limit

We derive an approximate relic neutrino asymmetry evolution equation that systematically incorporates repopulation processes from the full quantum kinetic equations (QKEs). It is shown that in the collision dominant epoch, the said equation reduces precisely to the expression obtained previously from the static/adiabatic approximation. The present treatment thus provides a rigorous justification for the seemingly incongruous assumptions of a negligible repopulation function and instantaneous repopulation sometimes employed in earlier works.Comment: RevTeX, 11 pages, no figure

Detailed study of BBN implications of neutrino oscillation generated neutrino asymmetries in some four neutrino models

We re-examine the evolution of neutrino asymmetries in several four neutrino models. The first case involves the direct creation of $L_{\nu_e}$ by $\nu_e \leftrightarrow \nu_s$ oscillations. In the second case, we consider the mass hierarchy $m_{\nu_\tau} \gg m_{\nu_\mu}, m_{\nu_e}, m_{\nu_s}$ where $\nu_\tau \leftrightarrow \nu_s$ oscillations generate a large $L_{\nu_\tau}$ and some of this asymmetry is converted into $L_{\nu_e}$ by $\nu_{\tau} \leftrightarrow \nu_{e}$ oscillations. We estimate the implications for BBN for a range of cosmologically interesting $\delta m^2$ values. The present paper improves on previous published work by taking into account the finite repopulation rate and the time dependence of the distortions to the neutrino momentum distributions. The treatment of chemical decoupling is also improved.Comment: Expanded discussion on the sign of the neutrino asymmetr

Long-Term Evolution of Massive Black Hole Binaries. II. Binary Evolution in Low-Density Galaxies

We use direct-summation N-body integrations to follow the evolution of binary black holes at the centers of galaxy models with large, constant-density cores. Particle numbers as large as 400K are considered. The results are compared with the predictions of loss-cone theory, under the assumption that the supply of stars to the binary is limited by the rate at which they can be scattered into the binary's influence sphere by gravitational encounters. The agreement between theory and simulation is quite good; in particular, we are able to quantitatively explain the observed dependence of binary hardening rate on N. We do not verify the recent claim of Chatterjee, Hernquist & Loeb (2003) that the hardening rate of the binary stabilizes when N exceeds a particular value, or that Brownian wandering of the binary has a significant effect on its evolution. When scaled to real galaxies, our results suggest that massive black hole binaries in gas-poor nuclei would be unlikely to reach gravitational-wave coalescence in a Hubble time.Comment: 13 pages, 8 figure

Analysis of measurement errors for a superconducting phase qubit

We analyze several mechanisms leading to errors in a course of measurement of a superconducting flux-biased phase qubit. Insufficiently long measurement pulse may lead to nonadiabatic transitions between qubit states $|1>$ and $|0>$, before tunneling through a reduced barrier is supposed to distinguish the qubit states. Finite (though large) ratio of tunneling rates for these states leads to incomplete discrimination between $|1>$ and $|0>$. Insufficiently fast energy relaxation after the tunneling of state $|1>$ may cause the repopulation of the quantum well in which only the state $|0>$ is supposed to remain. We analyze these types of measurement errors using analytical approaches as well as numerical solution of the time-dependent Schr\"{o}dinger equation.Comment: 14 pages, 14 figure

Anisotropic Stark Effect and Electric-Field Noise Suppression for Phosphorus Donor Qubits in Silicon

We report the use of novel, capacitively terminated coplanar waveguide (CPW) resonators to measure the quadratic Stark shift of phosphorus donor qubits in Si. We confirm that valley repopulation leads to an anisotropic spin-orbit Stark shift depending on electric and magnetic field orientations relative to the Si crystal. By measuring the linear Stark effect, we estimate the effective electric field due to strain in our samples. We show that in the presence of this strain, electric-field sources of decoherence can be non-negligible. Using our measured values for the Stark shift, we predict magnetic fields for which the spin-orbit Stark effect cancels the hyperfine Stark effect, suppressing decoherence from electric-field noise. We discuss the limitations of these noise-suppression points due to random distributions of strain and propose a method for overcoming them

Study of EIT resonances in an anti-relaxation coated Rb vapor cell

We demonstrate---experimentally and theoretically---that resonances obtained in electromagnetically induced transparency (EIT) can be both bright and dark. The experiments are done using magnetic sublevels of a hyperfine transition in the D$_1$ line of $^{87}$Rb. The degeneracy of the sublevels is removed by having a magnetic field of value 27 G. The atoms are contained in a room-temperature vapor cell with anti-relaxation coating on the walls. Theoretical analysis based on a two-region model reproduces the experimental spectrum quite well. This ability to have both bright and dark resonances promises applications in sub- and super-luminal propagation of light, and sensitive magnetometry.Comment: 16 pages, 9 figure

FHL2 regulates hematopoietic stem cell functions under stress conditions.

FHL2, a member of the four and one half LIM domain protein family, is a critical transcriptional modulator. Here, we identify FHL2 as a critical regulator of hematopoietic stem cells (HSCs) that is essential for maintaining HSC self-renewal under regenerative stress. We find that Fhl2 loss has limited effects on hematopoiesis under homeostatic conditions. In contrast, Fhl2-null chimeric mice reconstituted with Fhl2-null bone marrow cells developed abnormal hematopoiesis with significantly reduced numbers of HSCs, hematopoietic progenitor cells (HPCs), red blood cells and platelets as well as hemoglobin levels. In addition, HSCs displayed a significantly reduced self-renewal capacity and were skewed toward myeloid lineage differentiation. We find that Fhl2 loss reduces both HSC quiescence and survival in response to regenerative stress, probably as a consequence of Fhl2-loss-mediated downregulation of cyclin-dependent kinase-inhibitors, including p21(Cip) and p27(Kip1). Interestingly, FHL2 is regulated under the control of a tissue-specific promoter in hematopoietic cells and it is downregulated by DNA hypermethylation in the leukemia cell line and primary leukemia cells. Furthermore, we find that downregulation of FHL2 frequently occurs in myelodysplastic syndrome and acute myeloid leukemia patients, raising a possibility that FHL2 downregulation has a role in the pathogenesis of myeloid malignancies