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

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

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

Experimental and theoretical cross sections for positron scattering from the pentane isomers

10 págs.; 8 figs.; 3 tabs.Isomerism is ubiquitous in chemistry, physics, and biology. In atomic and molecular physics, in particular, isomer effects are well known in electron-impact phenomena; however, very little is known for positron collisions. Here we report on a set of experimental and theoretical cross sections for low-energy positron scattering from the three structural isomers of pentane: normal-pentane, isopentane, and neopentane. Total cross sections for positron scattering from normal-pentane and isopentane were measured at the University of Trento at incident energies between 0.1 and 50 eV. Calculations of the total cross sections, integral cross sections for elastic scattering, positronium formation, and electronic excitations plus direct ionization, as well as elastic differential cross sections were computed for all three isomers between 1 and 1000 eV using the independent atom model with screening corrected additivity rule. No definitive evidence of a significant isomer effect in positron scattering from the pentane isomers appears to be present. ©2016 AIP Publishing LLCG.G. and F.B. would like to acknowledge the Spanish Ministerio de Economía y Productividad (Project No. FIS2012-31230) and the European Science Foundation (COST Action Grants Nos. MP1002–Nano-IBCT and MC1301-CELINA) for financial support. Finally, L.C. thanks the Japan Society for the Promotion of Science for his fellowship.Peer Reviewe

Atomic resolution experimental phase information reveals extensive disorder and bound 2-methyl-2,4-pentanediol in Ca\u3csup\u3e2+\u3c/sup\u3e-calmodulin

Calmodulin (CaM) is the primary calcium signaling protein in eukaryotes and has been extensively studied using various biophysical techniques. Prior crystal structures have noted the presence of ambiguous electron density in both hydrophobic binding pockets of Ca2+-CaM, but no assignment of these features has been made. In addition, Ca2+-CaM samples many conformational substates in the crystal and accurately modeling the full range of this functionally important disorder is challenging. In order to characterize these features in a minimally biased manner, a 1.0 A resolution single-wavelength anomalous diffraction data set was measured for selenomethionine-substituted Ca2+-CaM. Density-modified electron-density maps enabled the accurate assignment of Ca2+-CaM main-chain and side-chain disorder. These experimental maps also substantiate complex disorder models that were automatically built using lowcontour features of model-phased electron density. Furthermore, experimental electron-density maps reveal that 2-methyl-2,4-pentanediol (MPD) is present in the C-terminal domain, mediates a lattice contact between N-terminal domains and may occupy the N-terminal binding pocket. The majority of the crystal structures of target-free Ca2+-CaM have been derived from crystals grown using MPD as a precipitant, and thus MPD is likely to be bound in functionally critical regions of Ca2+-CaM in most of these structures. The adventitious binding of MPD helps to explain differences between the Ca2+-CaM crystal and solution structures and is likely to favor more open conformations of the EF-hands in the crystal

Atomic resolution experimental phase information reveals extensive disorder and bound 2-methyl-2,4-pentanediol in Ca\u3csup\u3e2+\u3c/sup\u3e-calmodulin

Calmodulin (CaM) is the primary calcium signaling protein in eukaryotes and has been extensively studied using various biophysical techniques. Prior crystal structures have noted the presence of ambiguous electron density in both hydrophobic binding pockets of Ca2+-CaM, but no assignment of these features has been made. In addition, Ca2+-CaM samples many conformational substates in the crystal and accurately modeling the full range of this functionally important disorder is challenging. In order to characterize these features in a minimally biased manner, a 1.0 A resolution single-wavelength anomalous diffraction data set was measured for selenomethionine-substituted Ca2+-CaM. Density-modified electron-density maps enabled the accurate assignment of Ca2+-CaM main-chain and side-chain disorder. These experimental maps also substantiate complex disorder models that were automatically built using lowcontour features of model-phased electron density. Furthermore, experimental electron-density maps reveal that 2-methyl-2,4-pentanediol (MPD) is present in the C-terminal domain, mediates a lattice contact between N-terminal domains and may occupy the N-terminal binding pocket. The majority of the crystal structures of target-free Ca2+-CaM have been derived from crystals grown using MPD as a precipitant, and thus MPD is likely to be bound in functionally critical regions of Ca2+-CaM in most of these structures. The adventitious binding of MPD helps to explain differences between the Ca2+-CaM crystal and solution structures and is likely to favor more open conformations of the EF-hands in the crystal

Total cross-sections for positron and electron scattering from α-tetrahydrofurfuryl alcohol

Peer Reviewe

Elastic electron scattering from CF3I

Experimental results are reported for elastic differential and integral cross sections for electrons scattering from CF3I. These measurements were made at ten incident electron energies in the range 10–50 eV, with a scattered electron angular range of 20◦–135◦. Where possible, comparison is made to the only other comprehensive experimental set of results available in the literature and to calculated cross sections from the Schwinger multichannel with pseudopotentials method. In general, quite good agreement is found between the present results and those of the earlier studies