1,876 research outputs found
Etanercept, infliximab, and leflunomide in established rheumatoid arthritis: clinical experience using a structured follow up programme in southern Sweden.
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
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
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
Recommended from our members
Tracer concentration profiles measured in central London as part of the REPARTEE campaign
There have been relatively few tracer experiments carried out that have looked at vertical plume spread in urban areas. In this paper we present results from two tracer (cyclic perfluorocarbon) experiments carried out in 2006 and 2007 in central London centred on the BT Tower as part of the REPARTEE (Regent’s Park and Tower Environmental Experiment) campaign. The height of the tower gives a unique opportunity to study vertical dispersion profiles and transport times in central London. Vertical gradients are contrasted with the relevant Pasquill stability classes. Estimation of lateral advection and vertical mixing times are made and compared with previous measurements. Data are then compared with a simple operational dispersion model and contrasted with data taken in central London as part of the DAPPLE campaign. This correlates dosage with non-dimensionalised distance from source. Such analyses illustrate the feasibility of the use of these empirical correlations over these prescribed distances in central London
Interaction between perceptual color and color knowledge information in object recognition: Behavioral and electrophysiological evidence
The impact of reading and writing skills on a visuo-motor integration task: A comparison between illiterate and literate subjects
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
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
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
- …