1,082 research outputs found

    Cognitive behaviour therapy versus counselling intervention for anxiety in young people with high-functioning autism spectrum disorders: a pilot randomised controlled trial

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    The use of cognitive-behavioural therapy (CBT) as a treatment for children and adolescents with autism spectrum disorder (ASD) has been explored in a number of trials. Whilst CBT appears superior to no treatment or treatment as usual, few studies have assessed CBT against a control group receiving an alternative therapy. Our randomised controlled trial compared use of CBT against person-centred counselling for anxiety in 36 young people with ASD, ages 12–18. Outcome measures included parent- teacher- and self-reports of anxiety and social disability. Whilst each therapy produced improvements inparticipants, neither therapy was superior to the other to a significant degree on any measure. This is consistent with findings for adults

    The 'Harmonizing Optimal Strategy for Treatment of coronary artery stenosis - sAfety & effectiveneSS of drug-elUting stents & antiplatelet REgimen' (HOST-ASSURE) trial: study protocol for a randomized controlled trial

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    <p>Abstract</p> <p>Background</p> <p>Second-generation drug-eluting stents (DES) have raised the bar of clinical performance. These stents are mostly made from cobalt chromium alloy. A newer generation DES has been developed from platinum chromium alloy, but clinical data regarding the efficacy and safety of the platinum chromium-based everolimus-eluting stent (PtCr-EES) is limited, with no comparison data against the cobalt chromium-based zotarolimus-eluting stent (CoCr-ZES). In addition, an antiplatelet regimen is an integral component of medical therapy after percutaneous coronary intervention (PCI). A 1-week duration of doubling the dose of clopidogrel (double-dose antiplatelet therapy (DDAT)) was shown to improve outcome at 1 month compared with conventional dose in acute coronary syndrome (ACS) patients undergoing PCI. However in Asia, including Korea, the addition of cilostazol (triplet antiplatelet therapy (TAT)) is used more commonly than doubling the dose of clopidogrel in high-risk patients.</p> <p>Methods</p> <p>In the 'Harmonizing Optimal Strategy for Treatment of coronary artery stenosis - sAfety & effectiveneSS of drug-elUting stents & antiplatelet REgimen' (HOST-ASSURE) trial, approximately 3,750 patients are being prospectively and randomly assigned in a 2 Γ— 2 factorial design according to the type of stent (PtCr-EES vs CoCr-ZES) and antiplatelet regimen (TAT vs DDAT). The first primary endpoint is target lesion failure at 1 year for the stent comparison, and the second primary endpoint is net clinical outcome at 1 month for comparison of antiplatelet therapy regimen.</p> <p>Discussion</p> <p>The HOST-ASSURE trial is the largest study yet performed to directly compare the efficacy and safety of the PtCr-EES versus CoCr-ZES in an 'all-comers' population. In addition, this study will also compare the clinical outcome of TAT versus DDAT for 1-month post PCI.</p> <p>Trial registration</p> <p>ClincalTrials.gov number <a href="http://www.clinicaltrials.gov/ct2/show/NCT01267734">NCT01267734</a>.</p

    Cmr1/WDR76 defines a nuclear genotoxic stress body linking genome integrity and protein quality control

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    DNA replication stress is a source of genomic instability. Here we identify ​changed mutation rate 1 (​Cmr1) as a factor involved in the response to DNA replication stress in Saccharomyces cerevisiae and show that ​Cmr1β€”together with ​Mrc1/​Claspin, ​Pph3, the chaperonin containing ​TCP1 (CCT) and 25 other proteinsβ€”define a novel intranuclear quality control compartment (INQ) that sequesters misfolded, ubiquitylated and sumoylated proteins in response to genotoxic stress. The diversity of proteins that localize to INQ indicates that other biological processes such as cell cycle progression, chromatin and mitotic spindle organization may also be regulated through INQ. Similar to ​Cmr1, its human orthologue ​WDR76 responds to proteasome inhibition and DNA damage by relocalizing to nuclear foci and physically associating with CCT, suggesting an evolutionarily conserved biological function. We propose that ​Cmr1/​WDR76 plays a role in the recovery from genotoxic stress through regulation of the turnover of sumoylated and phosphorylated proteins

    Allopregnanolone-induced rise in intracellular calcium in embryonic hippocampal neurons parallels their proliferative potential

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    <p>Abstract</p> <p>Background</p> <p>Factors that regulate intracellular calcium concentration are known to play a critical role in brain function and neural development, including neural plasticity and neurogenesis. We previously demonstrated that the neurosteroid allopregnanolone (APΞ±; 5Ξ±-pregnan-3Ξ±-ol-20-one) promotes neural progenitor proliferation <it>in vitro </it>in cultures of rodent hippocampal and human cortical neural progenitors, and <it>in vivo </it>in triple transgenic Alzheimer's disease mice dentate gyrus. We also found that APΞ±-induced proliferation of neural progenitors is abolished by a calcium channel blocker, nifedipine, indicating a calcium dependent mechanism for the proliferation.</p> <p>Methods</p> <p>In the present study, we investigated the effect of APΞ± on the regulation of intracellular calcium concentration in E18 rat hippocampal neurons using ratiometric Fura2-AM imaging.</p> <p>Results</p> <p>Results indicate that APΞ± rapidly increased intracellular calcium concentration in a dose-dependent and developmentally regulated manner, with an EC<sub>50 </sub>of 110 Β± 15 nM and a maximal response occurring at three days <it>in vitro</it>. The stereoisomers 3Ξ²-hydroxy-5Ξ±-hydroxy-pregnan-20-one, and 3Ξ²-hydroxy-5Ξ²-hydroxy-pregnan-20-one, as well as progesterone, were without significant effect. APΞ±-induced intracellular calcium concentration increase was not observed in calcium depleted medium and was blocked in the presence of the broad spectrum calcium channel blocker La<sup>3+</sup>, or the L-type calcium channel blocker nifedipine. Furthermore, the GABA<sub>A </sub>receptor blockers bicuculline and picrotoxin abolished APΞ±-induced intracellular calcium concentration rise.</p> <p>Conclusion</p> <p>Collectively, these data indicate that APΞ± promotes a rapid, dose-dependent, stereo-specific, and developmentally regulated increase of intracellular calcium concentration in rat embryonic hippocampal neurons via a mechanism that requires both the GABA<sub>A </sub>receptor and L-type calcium channel. These data suggest that APΞ±-induced intracellular calcium concentration increase serves as the initiation mechanism whereby APΞ± promotes neurogenesis.</p

    Role for the Mammalian Swi5-Sfr1 Complex in DNA Strand Break Repair through Homologous Recombination

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    In fission yeast, the Swi5-Sfr1 complex plays an important role in homologous recombination (HR), a pathway crucial for the maintenance of genomic integrity. Here we identify and characterize mammalian Swi5 and Sfr1 homologues. Mouse Swi5 and Sfr1 are nuclear proteins that form a complex in vivo and in vitro. Swi5 interacts in vitro with Rad51, the DNA strand-exchange protein which functions during HR. By generating Swi5βˆ’/βˆ’ and Sfr1βˆ’/βˆ’ embryonic stem cell lines, we found that both proteins are mutually interdependent for their stability. Importantly, the Swi5-Sfr1 complex plays a role in HR when Rad51 function is perturbed in vivo by expression of a BRC peptide from BRCA2. Swi5βˆ’/βˆ’ and Sfr1βˆ’/βˆ’ cells are selectively sensitive to agents that cause DNA strand breaks, in particular ionizing radiation, camptothecin, and the Parp inhibitor olaparib. Consistent with a role in HR, sister chromatid exchange induced by Parp inhibition is attenuated in Swi5βˆ’/βˆ’ and Sfr1βˆ’/βˆ’ cells, and chromosome aberrations are increased. Thus, Swi5-Sfr1 is a newly identified complex required for genomic integrity in mammalian cells with a specific role in the repair of DNA strand breaks

    Improved Measurement of the Pseudoscalar Decay Constant fDsf_{D_{s}}

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    We present a new determination of the Ds decay constant, f_{Ds} using 5 million continuum charm events obtained with the CLEO II detector. Our value is derived from our new measured ratio of widths for Ds -> mu nu/Ds -> phi pi of 0.173+/- 0.021 +/- 0.031. Taking the branching ratio for Ds -> phi pi as (3.6 +/- 0.9)% from the PDG, we extract f_{Ds} = (280 +/- 17 +/- 25 +/- 34){MeV}. We compare this result with various model calculations.Comment: 23 page postscript file, postscript file also available through http://w4.lns.cornell.edu/public/CLN

    First Observation of Ο„β†’3πηντ\tau\to 3\pi\eta\nu_{\tau} and Ο„β†’f1πντ\tau\to f_{1}\pi\nu_{\tau} Decays

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    We have observed new channels for Ο„\tau decays with an Ξ·\eta in the final state. We study 3-prong tau decays, using the Ξ·β†’Ξ³Ξ³\eta\to\gamma\gamma and \eta\to 3\piz decay modes and 1-prong decays with two \piz's using the Ξ·β†’Ξ³Ξ³\eta\to\gamma\gamma channel. The measured branching fractions are \B(\tau^{-}\to \pi^{-}\pi^{-}\pi^{+}\eta\nu_{\tau}) =(3.4^{+0.6}_{-0.5}\pm0.6)\times10^{-4} and \B(\tau^{-}\to \pi^{-}2\piz\eta\nu_{\tau} =(1.4\pm0.6\pm0.3)\times10^{-4}. We observe clear evidence for f1→ηππf_1\to\eta\pi\pi substructure and measure \B(\tau^{-}\to f_1\pi^{-}\nu_{\tau})=(5.8^{+1.4}_{-1.3}\pm1.8)\times10^{-4}. We have also searched for Ξ·β€²(958)\eta'(958) production and obtain 90% CL upper limits \B(\tau^{-}\to \pi^{-}\eta'\nu_\tau)<7.4\times10^{-5} and \B(\tau^{-}\to \pi^{-}\piz\eta'\nu_\tau)<8.0\times10^{-5}.Comment: 11 page postscript file, postscript file also available through http://w4.lns.cornell.edu/public/CLN

    Search for the Decays B^0 -> D^{(*)+} D^{(*)-}

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    Using the CLEO-II data set we have searched for the Cabibbo-suppressed decays B^0 -> D^{(*)+} D^{(*)-}. For the decay B^0 -> D^{*+} D^{*-}, we observe one candidate signal event, with an expected background of 0.022 +/- 0.011 events. This yield corresponds to a branching fraction of Br(B^0 -> D^{*+} D^{*-}) = (5.3^{+7.1}_{-3.7}(stat) +/- 1.0(syst)) x 10^{-4} and an upper limit of Br(B^0 -> D^{*+} D^{*-}) D^{*\pm} D^\mp and B^0 -> D^+ D^-, no significant excess of signal above the expected background level is seen, and we calculate the 90% CL upper limits on the branching fractions to be Br(B^0 -> D^{*\pm} D^\mp) D^+ D^-) < 1.2 x 10^{-3}.Comment: 12 page postscript file also available through http://w4.lns.cornell.edu/public/CLNS, submitted to Physical Review Letter

    ΛΛˉ\Lambda\bar{\Lambda} Production in Two-Photon Interactions at CLEO

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    Using the CLEO detector at the Cornell e+eβˆ’e^+e^- storage ring, CESR, we study the two-photon production of ΛΛˉ\Lambda \bar{\Lambda}, making the first observation of γγ→ΛΛˉ\gamma \gamma \to \Lambda \bar{\Lambda}. We present the cross-section for γγ→ΛΛˉ \gamma \gamma \to \Lambda \bar{\Lambda} as a function of the Ξ³Ξ³\gamma \gamma center of mass energy and compare it to that predicted by the quark-diquark model.Comment: 10 pages, postscript file also available through http://w4.lns.cornell.edu/public/CLN
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