6,761 research outputs found

    Reconstitution of Calcium-Triggered Synaptic Vesicle Fusion

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    Comparison of Allen Carr's Easyway programme with a specialist behavioural and pharmacological smoking cessation support service: a randomized controlled trial.

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    BACKGROUND AND AIMS: A combination of behavioural and pharmacological support is judged to be the optimal approach for assisting smoking cessation. Allen Carr's Easyway (ACE) is a single-session pharmacotherapy-free programme that has been in operation internationally for 38 years. We compared the effectiveness of ACE with specialist behavioural and pharmacological support delivered to the national standard in England. DESIGN: A two-arm, parallel-group, single-blind, randomized controlled trial. SETTING: London, UK, between February 2017 and May 2018. PARTICIPANTS: A total of 620 participants (310 in ACE and 310 in the combined behavioural and pharmacological support condition) were included in the analysis. Adult (≥ 18 years) smokers wanting to quit were randomized in a 1 : 1 ratio. Mean age for the total sample was 40.8 years, with 53.4% being male. Participant baseline characteristics (ethnicity, educational level, number of previous quit attempts, nicotine dependence) were evenly balanced between treatment groups. INTERVENTION AND COMPARATOR: The intervention was the ACE method of stopping smoking. This centres on a 4.5-6-hour session of group-based support, alongside subsequent text messages and top-up sessions if needed. It aims to make it easy to stop smoking by convincing smokers that smoking provides no benefits for them. The comparator was a specialist stop smoking service (SSS) providing behavioural and pharmacological support in accordance with national standards. MEASUREMENTS: The primary outcome was self-reported continuous abstinence for 26 weeks from the quit/quit re-set date verified by exhaled breath carbon monoxide measurement < 10 parts per million (p.p.m.). Primary analysis was by intention to treat. Secondary outcomes were: use of pharmacotherapy, adverse events and continuous abstinence up to 4 and 12 weeks. FINDINGS: A total of 468 participants attended treatment (255 ACE versus 213 SSS, P < 0.05). Of those who did attend treatment, 100 completed 6-month measures (23.7% ACE versus 20.7% SSS). Continuous abstinence to 26 weeks was 19.4% (60 of 310) in the ACE intervention and 14.8% (46 of 310) in the SSS intervention [risk difference for ACE versus SSS 4.5% (95% confidence interval (CI) = -1.4 to 10.4%, odds ratio (OR) = 1.38)]. The Bayes factor for superiority of the ACE condition was 1.24. CONCLUSION: There was no clear evidence of a difference in the efficacies of the Allen Carr's Easyway (ACE) and specialist smoking cessation support involving behavioural support and pharmacotherapy

    Genome engineering of stem cells for autonomously regulated, closed-loop delivery of biologic drugs

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    Chronic inflammatory diseases such as arthritis are characterized by dysregulated responses to pro-inflammatory cytokines such as interleukin-1 (IL-1) and tumor necrosis factor α (TNF-α). Pharmacologic anti-cytokine therapies are often effective at diminishing this inflammatory response but have significant side effects and are used at high, constant doses that do not reflect the dynamic nature of disease activity. Using the CRISPR/Cas9 genome-engineering system, we created stem cells that antagonize IL-1- or TNF-α-mediated inflammation in an autoregulated, feedback-controlled manner. Our results show that genome engineering can be used successfully to rewire endogenous cell circuits to allow for prescribed input/output relationships between inflammatory mediators and their antagonists, providing a foundation for cell-based drug delivery or cell-based vaccines via a rapidly responsive, autoregulated system. The customization of intrinsic cellular signaling pathways in stem cells, as demonstrated here, opens innovative possibilities for safer and more effective therapeutic approaches for a wide variety of diseases

    Ab-initio electron scattering cross-sections and transport in liquid xenon

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    Ab-initio electron - liquid phase xenon fully differential cross-sections for electrons scattering in liquid xenon are developed from a solution of the Dirac-Fock scattering equations, using a recently developed framework [1] which considers multipole polarizabilities, a non-local treatment of exchange, and screening and coherent scattering effects. A multi-term solution of Boltzmann's equation accounting for the full anisotropic nature of the differential cross-section is used to calculate transport properties of excess electrons in liquid xenon. The results were found to agree to within 25% of the measured mobilities and characteristic energies over the reduced field range of 10^{-4} to 1 Td. The accuracies are comparable to those achieved in the gas phase. A simple model, informed by highly accurate gas-phase cross-sections, is presented to transform highly accurate gas-phase cross-sections to improve the liquid cross-sections, which was found to enhance the accuracy of the transport coefficient calculations.Comment: 26 pages, 9 figures. arXiv admin note: text overlap with arXiv:1503.0037

    Assessing Risk to Researchers: Using the Case of Sexuality Research to Inform Research Ethics Board Guidelines

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    Das Augenmerk von Ethikkommissionen liegt typischerweise auf dem Schutz der Teilnehmenden. Zunehmend werden jedoch auch Risiken diskutiert, welche Forschende selbst betreffen. Sollten Ethikkommissionen festlegen, welche Risiken für Forschende akzeptabel sind? Falls ja, worauf sollte sich ihre Einschätzung stützen? Aktuell scheinen die Implikationen einer Risikoeinschätzung für Forschende durch Ethikkommissionen zu wenig theoretisch durchdacht. An den Ansatz der kritischen Queer Studies anschließend zeigen wir am Beispiel von Forschung zu Sexualität mögliche Probleme auf, die im Zuge der Einschätzung von Risiken für Forschende auftreten können. Wir stellen hierfür zwei zentrale Fragen der Ethikbegutachtung in den Fokus: 1. Wie verhält sich das Risiko der Teilnahme an Forschung zu alltäglichen Risiken? 2. In welchem Verhältnis stehen mögliche Schädigungen zu dem antizipierten Nutzen der Studie?Teilweise werden Untersuchungen zu Sexualität sowohl für Teilnehmende als auch für Forschende als besonders risikobehaftet erachtet und deshalb kritischer geprüft als andere Forschungsvorhaben. Angesichts der hier inhärenten moralischen Untertöne ethischer Verfahren argumentieren wir, dass falls eine Risikoeinschätzung vorgenommen werden muss, diese in den Aufgabenbereich pädagogischer Betreuungsverhältnisse oder der Arbeitssicherheit, nicht aber in den von Ethikkommissionen fallen sollte. Auch eine Risikoschulung sollte gegebenenfalls für alle Forschenden gelten, unabhängig von dem spezifischen Forschungsgebiet.Research Ethics Boards (REBs) typically focus on ensuring the safety of participants. Increasingly, the risk that research poses to researchers is also discussed. Should REBs involve themselves in determining the degree of allowable researcher risk, and if so, upon what should they base that assessment? The evaluation of researcher safety does not appear to be standardized in any national REB protocols. The implications of REB review of researcher risks remain undertheorized. With a critical queer framework, we use the example of sexuality research to illustrate problems that could arise if researcher risk is assessed. We concentrate on two core research ethics guidelines: 1. How research risk compares to the risks of everyday life. 2. How potential harms compare to the anticipated research benefits. Some argue that sexuality research is more deeply scrutinized than research in other fields, viewed as inherently risky for both participants and researchers. The example of sexuality research helps make explicit the moral undertones of procedural ethics. With these moral undertones in mind, we argue that if adopted, researcher risk guidelines should be the purview of pedagogical relationships or workplace safety requirements, not REBs. Any risk training should be universally required regardless of the research area

    Low-energy elastic electron interactions with pyrimidine

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    We present results of measurements and calculations of elastic electron scattering from pyrimidine in the energy range 3–50 eV. Absolute differential and integral elastic cross sections have been measured using a crossed electron-molecule beam spectrometer and the relative flow technique. The measured cross sections are compared with results of calculations using the well-known Schwinger variational technique and an independent-atom model. Agreement between the measured differential cross sections and the results of the Schwinger calculations is good at lower energies but less satisfactory at higher energies where inelastic channels that should be open are kept closed in the calculations

    NSF and p97/VCP: similar at first, different at last

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    AbstractN-Ethylmaleimide sensitive factor (NSF) and p97/valosin-containing protein (VCP) are distantly related members of the ATPases associated with a variety of cellular activities (AAA) family of proteins. While both proteins have been implied in cellular morphology changes involving membrane compartments or vesicles, more recent evidence seems to imply that NSF is primarily involved in the soluble NSF attachment receptor (SNARE)-mediated vesicle fusion by disassembling the SNARE complex whereas p97/VCP is primarily involved in the extraction of membrane proteins. These functional differences are now corroborated by major structural differences based on recent crystallographic and cryo-electron microscopy studies. This review discusses these recent findings
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