1,876 research outputs found

    Etanercept, infliximab, and leflunomide in established rheumatoid arthritis: clinical experience using a structured follow up programme in southern Sweden.

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    OBJECTIVE: To explore the feasibility of prospectively monitoring treatment efficacy and tolerability of infliximab, etanercept, and leflunomide over a two year period in patients with established rheumatoid arthritis (RA) in clinical practice using a structured protocol. METHODS: All patients with RA at seven centres in southern Sweden, for whom at least two disease modifying antirheumatic drugs, including methotrexate, had failed or not been tolerated, who started treatment with either infliximab, etanercept, or leflunomide were included. They were evaluated at predefined times using a standardised protocol including items required for evaluating response to the American College of Rheumatology (ACR) or EULAR criteria. All adverse events were recorded using World Health Organisation terminology. Concomitant treatment and survival while receiving a drug were recorded. RESULTS: During the study 166 patients were treated with etanercept, 135 with infliximab, and 103 with leflunomide. Treatment response as determined by the ACR and EULAR response criteria was similar for the tumour necrosis factor (TNF) blockers. The TNF blockers performed significantly better than leflunomide both as determined by the response criteria and by survival on drug analysis. Thus 79% and 75% continued to receive etanercept or infliximab compared with 22% of patients who started leflunomide after 20 months. The spectrum of side effects did not differ from those previously reported in the clinical trials. The initial two year experience of a protocol for postmarketing surveillance of etanercept, infliximab, and leflunomide shows that a structured protocol with central data handling can be used in clinical practice for documenting the performance of newly introduced drugs. CONCLUSIONS: Efficacy data for the TNF blockers comply with results in clinical trials, whereas leflunomide appeared to perform worse than in clinical trials. Prolonged monitoring is required to identify possible rare side effects

    A fluorophore attached to nicotinic acetylcholine receptor beta M2 detects productive binding of agonist to the alpha delta site

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    To study conformational transitions at the muscle nicotinic acetylcholine (ACh) receptor (nAChR), a rhodamine fluorophore was tethered to a Cys side chain introduced at the beta-19' position in the M2 region of the nAChR expressed in Xenopus oocytes. This procedure led to only minor changes in receptor function. During agonist application, fluorescence increased by (Delta-F/F) approximate to 10%, and the emission peak shifted to lower wavelengths, indicating a more hydrophobic environment for the fluorophore. The dose-response relations for Delta-F agreed well with those for epibatidine-induced currents, but were shifted approximate to 100-fold to the left of those for ACh-induced currents. Because (i) epibatidine binds more tightly to the alpha-gamma-binding site than to the alpha-delta site and (ii) ACh binds with reverse-site selectivity, these data suggest that Delta-F monitors an event linked to binding specifically at the alpha-delta-subunit interface. In experiments with flash-applied agonists, the earliest detectable Delta-F occurs within milliseconds, i.e., during activation. At low [ACh] (less than or equal to 10 muM), a phase of Delta-F occurs with the same time constant as desensitization, presumably monitoring an increased population of agonist-bound receptors. However, recovery from Delta-F is complete before the slowest phase of recovery from desensitization (time constant approximate to 250 s), showing that one or more desensitized states have fluorescence like that of the resting channel. That conformational transitions at the alpha-delta-binding site are not tightly coupled to channel activation suggests that sequential rather than fully concerted transitions occur during receptor gating. Thus, time-resolved fluorescence changes provide a powerful probe of nAChR conformational changes

    Photon Assisted Tunneling of Zero Modes in a Majorana Wire

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    Hybrid nanowires with proximity-induced superconductivity in the topological regime host Majorana zero modes (MZMs) at their ends, and networks of such structures can produce topologically protected qubits. In a double-island geometry where each segment hosts a pair of MZMs, inter-pair coupling mixes the charge parity of the islands and opens an energy gap between the even and odd charge states at the inter-island charge degeneracy. Here, we report on the spectroscopic measurement of such an energy gap in an InAs/Al double-island device by tracking the position of the microwave-induced quasiparticle (qp) transitions using a radio-frequency (rf) charge sensor. In zero magnetic field, photon assisted tunneling (PAT) of Cooper pairs gives rise to resonant lines in the 2e-2e periodic charge stability diagram. In the presence of a magnetic field aligned along the nanowire, resonance lines are observed parallel to the inter-island charge degeneracy of the 1e-1e periodic charge stability diagram, where the 1e periodicity results from a zero-energy sub-gap state that emerges in magnetic field. Resonant lines in the charge stability diagram indicate coherent photon assisted tunneling of single-electron states, changing the parity of the two islands. The dependence of resonant frequency on detuning indicates a sizable (GHz-scale) hybridization of zero modes across the junction separating islands

    The impact of reading and writing skills on a visuo-motor integration task: A comparison between illiterate and literate subjects

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    Previous studies have shown a significant association between reading skills and the performance on visuo-motor tasks. In order to clarify whether reading and writing skills modulate non-linguistic domains, we investigated the performance of two literacy groups on a visuo-motor integration task with non-linguistic stimuli. Twenty-one illiterate participants and twenty matched literate controls were included in the experiment. Subjects were instructed to use the right or the left index finger to point to and touch a randomly presented target on the right or left side of a touch screen. The results showed that the literate subjects were significantly faster in detecting and touching targets on the left compared to the right side of the screen. In contrast, the presentation side did not affect the performance of the illiterate group. These results lend support to the idea that having acquired reading and writing skills, and thus a preferred left-to-right reading direction, influences visual scanning. (JINS, 2007, 13, 359–36

    Non-Perturbative Effects on a Fractional D3-Brane

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    In this note we study the N=1 abelian gauge theory on the world volume of a single fractional D3-brane. In the limit where gravitational interactions are not completely decoupled we find that a superpotential and a fermionic bilinear condensate are generated by a D-brane instanton effect. A related situation arises for an isolated cycle invariant under an orientifold projection, even in the absence of any gauge theory brane. Moreover, in presence of supersymmetry breaking background fluxes, such instanton configurations induce new couplings in the 4-dimensional effective action, including non-perturbative contributions to the cosmological constant and non-supersymmetric mass terms.Comment: 18 pages, v3: refs adde

    Higgs decay with monophoton + MET signature from low scale supersymmetry breaking

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    We study the decay of a standard model-like Higgs boson into a gravitino and a neutralino, which subsequently decays promptly into another gravitino and a photon. Such a decay can be important in scenarios where the supersymmetry breaking scale is of the order of a few TeV, and in the region of low transverse momenta of the photon, it may provide the dominant contribution to the final state with a photon and two gravitinos. We estimate the relevant standard model backgrounds and the prospects for discovering this Higgs decay through a photon and missing transverse energy signal at the LHC in terms of a simplified model. We also give an explicit model with manifest, but spontaneously broken, supersymmetry in which the usual MSSM soft terms are promoted to supersymmetric operators involving a dynamical goldstino supermultiplet. This model can give rise to a SM-like CP-even neutral Higgs particle with a mass of 125 GeV, without requiring substantial radiative corrections, and with couplings sufficiently large for a signal discovery through the above mentioned Higgs decay channel with the upcoming data from the LHC.Comment: 28 pages, 5 figures, 4 tables; v2: updated to JHEP version, references adde
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