New players in the preventive treatment of migraine.

Migraine is a common, chronic disorder of the brain causing much disability, as well as personal, familial and societal impact. Several oral preventive agents are available in different countries for the prevention of migraine, but none have performed better than 50% improvement in 50% of patients in a clinical trial. Additionally, each has various possible adverse events making their tolerability less than optimal. Recently, three monoclonal antibodies targeting the calcitonin gene-related peptide (CGRP) ligand (LY2951742, ALD403 and TEV-48125) and one targeting the CGRP receptor (AMG 334) have completed phase 2 trials, and the results have been reported. These early results show them all to be somewhat more effective than placebo, with no serious adverse events. Three have been studied for episodic migraine, and only TEV-48125 has been studied for both high frequency episodic and chronic migraine. Moreover, preliminary data suggests that neurostimulation is effective in migraine treatment, including stimulation of the sphenopalatine ganglion, transcutaneous supraorbital and supratrochlear nerve, and transcutaneous vagus nerve. In this article, these innovative therapies will be reviewed

Inter- and intragrain currents in bulk melt-grown YBaCuO rings

A simple contactless method suitable to discern between the intergrain (circular) current, which flows in the thin superconducting ring, and the intragrain current, which does not cross the weakest link, has been proposed. At first, we show that the intergrain current may directly be estimated from the magnetic flux density $B(\pm z_0)$ measured by the Hall sensor positioned in the special points $\pm z_0$ above/below the ring center. The experimental and the numerical techniques to determine the value $z_0$ are discussed. Being very promising for characterization of a current flowing across the joints in welded YBaCuO rings (its dependencies on the temperature and the external magnetic field as well as the time dissipation), the approach has been applied to study corresponding properties of the intra- and intergrain currents flowing across the $a$-twisted grain boundaries which are frequent in bulk melt-textured YBaCuO samples. We present experimental data related to the flux penetration inside a bore of MT YBaCuO rings both in the non-magnetized, virgin state and during the field reversal. The shielding properties and their dependence on external magnetic fields are also studied. Besides, we consider the flux creep effects and their influence on the current re-distribution during a dwell.Comment: 13 pages, 16 figures (EPS), RevTeX4. In the revised version, corrections to perturbing effects near the weak links are introduced, one more figure is added. lin

Effects of Space Charge, Dopants, and Strain Fields on Surfaces and Grain Boundaries in YBCO Compounds

Statistical thermodynamical and kinetically-limited models are applied to study the origin and evolution of space charges and band-bending effects at low angle [001] tilt grain boundaries in YBa$_2$Cu$_3$O$_7$ and the effects of Ca doping upon them. Atomistic simulations, using shell models of interatomic forces, are used to calculate the energetics of various relevant point defects. The intrinsic space charge profiles at ideal surfaces are calculated for two limits of oxygen contents, i.e. YBa$_2$Cu$_3$O$_6$ and YBa$_2$Cu$_3$O$_7$. At one limit, O$_6$, the system is an insulator, while at O$_7$, a metal. This is analogous to the intrinsic and doping cases of semiconductors. The site selections for doping calcium and creating holes are also investigated by calculating the heat of solution. In a continuum treatment, the volume of formation of doping calcium at Y-sites is computed. It is then applied to study the segregation of calcium ions to grain boundaries in the Y-123 compound. The influences of the segregation of calcium ions on space charge profiles are finally studied to provide one guide for understanding the improvement of transport properties by doping calcium at grain boundaries in Y-123 compound.Comment: 13 pages, 5 figure

Critical currents in Josephson junctions with macroscopic defects

The critical currents in Josephson junctions of conventional superconductors with macroscopic defects are calculated for different defect critical current densities as a function of the magnetic field. We also study the evolution of the different modes with the defect position, at zero external field. We study the stability of the solutions and derive simple arguments, that could help the defect characterization. In most cases a reentrant behavior is seen, where both a maximum and a minimum current exist.Comment: 17 pages with 16 figures, submitted to Supercond. Sci. Techno

The atomic structure of large-angle grain boundaries Σ5\Sigma 5 and Σ13\Sigma 13 in YBa2Cu3O7−δ{\rm YBa_2Cu_3O_{7-\delta}} and their transport properties

We present the results of a computer simulation of the atomic structures of large-angle symmetrical tilt grain boundaries (GBs) $\Sigma 5$ (misorientation angles \q{36.87}{^{\circ}} and \q{53.13}{^{\circ}}), $\Sigma 13$ (misorientation angles \q{22.62}{^{\circ}} and \q{67.38}{^{\circ}}). The critical strain level $\epsilon_{crit}$ criterion (phenomenological criterion) of Chisholm and Pennycook is applied to the computer simulation data to estimate the thickness of the nonsuperconducting layer ${\rm h_n}$ enveloping the grain boundaries. The ${\rm h_n}$ is estimated also by a bond-valence-sum analysis. We propose that the phenomenological criterion is caused by the change of the bond lengths and valence of atoms in the GB structure on the atomic level. The macro- and micro- approaches become consistent if the $\epsilon_{crit}$ is greater than in earlier papers. It is predicted that the symmetrical tilt GB $\Sigma5$ \theta = \q{53.13}{^{\circ}} should demonstrate a largest critical current across the boundary.Comment: 10 pages, 2 figure

Self-organized current transport through low angle grain boundaries in YBa2_2Cu3_3O7−δ_{7-\delta} thin films, studied magnetometrically

The critical current density flowing across low angle grain boundaries in YBa$_2$Cu$_3$O$_{7-\delta}$ thin films has been studied magnetometrically. Films (200 nm thickness) were deposited on SrTiO$_3$ bicrystal substrates containing a single [001] tilt boundary, with angles of 2, 3, 5, and 7 degrees, and the films were patterned into rings. Their magnetic moments were measured in applied magnetic fields up to 30 kOe at temperatures of 5 - 95 K; current densities of rings with or without grain boundaries were obtained from a modified critical state model. For rings containing 5 and 7 degree boundaries, the magnetic response depends strongly on the field history, which arises in large part from self-field effects acting on the grain boundary.Comment: 8 pages, including 7 figure

Male and female sex hormones in primary headaches

Background: The three primary headaches, tension-type headache, migraine and cluster headache, occur in both genders, but all seem to have a sex-specific prevalence. These gender differences suggest that both male and female sex hormones could have an influence on the course of primary headaches. This review aims to summarise the most relevant and recent literature on this topic. Methods: Two independent reviewers searched PUBMED in a systematic manner. Search strings were composed using the terms LH, FSH, progesteron, estrogen, DHEA, prolactin, testosterone, androgen, headach, migrain, "tension type" or cluster. A timeframe was set limiting the search to articles published in the last 20 years, after January 1st 1997. Results: Migraine tends to follow a classic temporal pattern throughout a woman's life corresponding to the fluctuation of estrogen in the different reproductive stages. The estrogen withdrawal hypothesis forms the basis for most of the assumptions made on this behalf. The role of other hormones as well as the importance of sex hormones in other primary headaches is far less studied. Conclusion: The available literature mainly covers the role of sex hormones in migraine in women. Detailed studies especially in the elderly of both sexes and in cluster headache and tension-type headache are warranted to fully elucidate the role of these hormones in all primary headaches

Theory of c-axis Josephson tunneling in d-wave superconductors

The temperature and angular dependence of the c-axis Josephson current and the superfluid density in layered d-wave superconductors are studied within the framework of an extended Ambegaokar-Baratoff formalism. In particular, the effects of angle-dependent tunneling matrix elements and Andreev scattering at grain boundaries are taken into account. These lead to strong corrections of the low-temperature behavior of the plasma frequency and the Josephson current. Recent c-axis measurements on the cuprate high-temperature superconductors HgBa_2CaCu_{1+\delta} and Bi_2Sr_2CaCu_2O_{8+\delta} can therefore be interpreted to be consistent with a d-wave order parameter.Comment: Revtex, 4 pages with 4 eps figures, to appear in PRB R

Advantageous grain boundaries in iron pnictide superconductors

High critical temperature superconductors have zero power consumption and could be used to produce ideal electric power lines. The principal obstacle in fabricating superconducting wires and tapes is grain boundaries-the misalignment of crystalline orientations at grain boundaries, which is unavoidable for polycrystals, largely deteriorates critical current density. Here, we report that High critical temperature iron pnictide superconductors have advantages over cuprates with respect to these grain boundary issues. The transport properties through well-defined bicrystal grain boundary junctions with various misorientation angles (thetaGB) were systematically investigated for cobalt-doped BaFe2As2 (BaFe2As2:Co) epitaxial films fabricated on bicrystal substrates. The critical current density through bicrystal grain boundary (JcBGB) remained high (> 1 MA/cm2) and nearly constant up to a critical angle thetac of ~9o, which is substantially larger than the thetac of ~5o for YBCO. Even at thetaGB > thetac, the decay of JcBGB was much smaller than that of YBCO.Comment: to appear in Nature Communication

Andreev reflection in layered structures: implications for high T_c grain boundary Josephson junctions

Andreev reflection is investigated in layered anisotropic normal metal / superconductor (N/S) systems in the case of an energy gap \Delta in S not negligible with respect to the Fermi energy E_F, as it probably occurs with high critical temperature superconductors (HTS). We find that in these limits retro-reflectivity, which is a fundamental feature of Andreev reflection, is broken modifying sensitively transport across S/N interfaces. We discuss the consequences for supercurrents in HTS Josephson junctions and for the midgap states in S-N contactsComment: 4 pages, 4 figures, to be published in Phys. Rev.