Repeated ovarian stimulation with corifollitropin alfa in patients in a GnRH antagonist protocol: no concern for immunogenicity

BACKGROUND One injection of corifollitropin alfa replaces the first seven daily FSH injections in controlled ovarian stimulation (COS) cycles. Repeated treatment with therapeutic proteins may cause immune responses or hypersensitivity reactions. We assessed the immunogenicity and safety of corifollitropin alfa treatment in up to three COS cycles. METHODS In this multicentre, phase III uncontrolled trial, patients (>60 kg) started treatment with one injection of 150 µg corifollitropin alfa on cycle Day 2 or 3 of menses and 0.25 mg ganielix on stimulation Day 5 or 6. Primary outcome measures were antibody formation against corifollitropin alfa (using highly sensitive radioimmunoprecipitation assay), hypersensitivity reactions, local tolerance and adverse events (AEs). RESULTS First, second and third COS cycles were started by 682, 375 and 198 patients, respectively. No clinically relevant immunogenicity or drug-related hypersensitivity was observed. For 192 patients undergoing their third cycle a post-treatment blood sample was negative in the anti-corifollitropin antibody assay, resulting in an upper limit of the one-sided 95% confidence interval (CI) of 1.5%. Most frequent AEs were procedural pain (17.7%, 95% CI: 14.9–20.8%), headache (9.1%, 95% CI: 7.0–11.5%) and pelvic pain (7.6%, 95% CI: 5.7–9.9%). Cumulative ongoing pregnancy rate after three cycles, including frozen-thawed embryo transfer cycles and spontaneous pregnancies, was 61% (95% CI: 56–65%) after censoring for patients who discontinued. CONCLUSIONS Treatment with corifollitropin alfa can safely and effectively initiate and sustain ovarian stimulation during the first 7 days of COS in normal responder patients undergoing up to three treatment cycles, without concerns of immunogenicity.Robert J. Norman, Fernando Zegers-Hochschild, Bruno S. Salle, Jolanda Elbers, Esther Heijnen, Maya Marintcheva-Petrova, and Bernadette Mannaerts for the Trust Investigator

Aperiodic dynamical decoupling sequences in presence of pulse errors

Dynamical decoupling (DD) is a promising tool for preserving the quantum states of qubits. However, small imperfections in the control pulses can seriously affect the fidelity of decoupling, and qualitatively change the evolution of the controlled system at long times. Using both analytical and numerical tools, we theoretically investigate the effect of the pulse errors accumulation for two aperiodic DD sequences, the Uhrig's DD UDD) protocol [G. S. Uhrig, Phys. Rev. Lett. {\bf 98}, 100504 (2007)], and the Quadratic DD (QDD) protocol [J. R. West, B. H. Fong and D. A. Lidar, Phys. Rev. Lett {\bf 104}, 130501 (2010)]. We consider the implementation of these sequences using the electron spins of phosphorus donors in silicon, where DD sequences are applied to suppress dephasing of the donor spins. The dependence of the decoupling fidelity on different initial states of the spins is the focus of our study. We investigate in detail the initial drop in the DD fidelity, and its long-term saturation. We also demonstrate that by applying the control pulses along different directions, the performance of QDD protocols can be noticeably improved, and explain the reason of such an improvement. Our results can be useful for future implementations of the aperiodic decoupling protocols, and for better understanding of the impact of errors on quantum control of spins.Comment: updated reference

A New Limit on the Neutrinoless DBD of 130Te

We report the present results of CUORICINO a cryogenic experiment on neutrinoless double beta decay (DBD) of 130Te consisting of an array of 62 crystals of TeO2 with a total active mass of 40.7 kg. The array is framed inside of a dilution refrigerator, heavily shielded against environmental radioactivity and high-energy neutrons, and operated at a temperature of ~8 mK in the Gran Sasso Underground Laboratory. Temperature pulses induced by particle interacting in the crystals are recorded and measured by means of Neutron Transmutation Doped thermistors. The gain of each bolometer is stabilized with voltage pulses developed by a high stability pulse generator across heater resistors put in thermal contact with the absorber. The calibration is performed by means of two thoriated wires routinely inserted in the set-up. No evidence for a peak indicating neutrinoless DBD of 130Te is detected and a 90% C.L. lower limit of 1.8E24 years is set for the lifetime of this process. Taking largely into account the uncertainties in the theoretical values of nuclear matrix elements, this implies an upper boud on the effective mass of the electron neutrino ranging from 0.2 to 1.1 eV. This sensitivity is similar to those of the 76Ge experiments.Comment: 4 pages, 2 figure

Hardy's inequality for functions vanishing on a part of the boundary

We develop a geometric framework for Hardy's inequality on a bounded domain when the functions do vanish only on a closed portion of the boundary.Comment: 26 pages, 2 figures, includes several improvements in Sections 6-8 allowing to relax the assumptions in the main results. Final version published at http://link.springer.com/article/10.1007%2Fs11118-015-9463-

Mean-field phase diagram of disordered bosons in a lattice at non-zero temperature

Bosons in a periodic lattice with on-site disorder at low but non-zero temperature are considered within a mean-field theory. The criteria used for the definition of the superfluid, Mott insulator and Bose glass are analysed. Since the compressibility does never vanish at non-zero temperature, it can not be used as a general criterium. We show that the phases are unambiguously distinguished by the superfluid density and the density of states of the low-energy exitations. The phase diagram of the system is calculated. It is shown that even a tiny temperature leads to a significant shift of the boundary between the Bose glass and superfluid

Electron spin dynamics in quantum dots and related nanostructures due to hyperfine interaction with nuclei

We review and summarize recent theoretical and experimental work on electron spin dynamics in quantum dots and related nanostructures due to hyperfine interaction with surrounding nuclear spins. This topic is of particular interest with respect to several proposals for quantum information processing in solid state systems. Specifically, we investigate the hyperfine interaction of an electron spin confined in a quantum dot in an s-type conduction band with the nuclear spins in the dot. This interaction is proportional to the square modulus of the electron wave function at the location of each nucleus leading to an inhomogeneous coupling, i.e. nuclei in different locations are coupled with different strength. In the case of an initially fully polarized nuclear spin system an exact analytical solution for the spin dynamics can be found. For not completely polarized nuclei, approximation-free results can only be obtained numerically in sufficiently small systems. We compare these exact results with findings from several approximation strategies.Comment: 26 pages, 9 figures. Topical Review to appear in J. Phys.: Condens. Matte

Groups of diffeomorphisms and geometric loops of manifolds over ultra-normed fields

The article is devoted to the investigation of groups of diffeomorphisms and loops of manifolds over ultra-metric fields of zero and positive characteristics. Different types of topologies are considered on groups of loops and diffeomorphisms relative to which they are generalized Lie groups or topological groups. Among such topologies pairwise incomparable are found as well. Topological perfectness of the diffeomorphism group relative to certain topologies is studied. There are proved theorems about projective limit decompositions of these groups and their compactifications for compact manifolds. Moreover, an existence of one-parameter local subgroups of diffeomorphism groups is investigated.Comment: Some corrections excluding misprints in the article were mad

MAXIMA: A balloon-borne cosmic microwave background anisotropy experiment

Published versio

A Cryogenic Underground Observatory for Rare Events: Cuore, an Update

CUORE is a proposed tightly packed array of 1000 TeO_{2} bolometers, each being a cube 5 cm on a side with a mass of 750 gms. The array consists of 25 vertical towers, arranged in a square, of 5 towers by 5 towers, each containing 10 layers of 4 crystals. The design of the detector is optimized for ultralow- background searches for neutrinoless double beta decay of ^{130}Te (33.8% abundance), cold dark matter, solar axions, and rare nuclear decays. A preliminary experiment involving 20 crystals of various sizes (MIBETA) has been completed, and a single CUORE tower is being constructed as a smaller scale experiment called CUORICINO. The expected performance and sensitivity, based on Monte Carlo simulations and extrapolations of present results, are reported.Comment: in press: Nucl. Phys. of Russian Academy of Sc