1,263 research outputs found

    Evaluating possible intended and unintended consequences of the implementation of alcohol minimum unit pricing (MUP) in Scotland: a natural experiment protocol

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    Introduction Scotland is the first country to carry out a national implementation of minimum unit pricing (MUP) for alcohol. MUP aims to reduce alcohol-related harms, which are high in Scotland compared with Western Europe, and to improve health equalities. MUP is a minimum retail price per unit of alcohol. That approach targets high-risk alcohol users. This work is key to a wider evaluation that will determine whether MUP continues. There are three study components.Methods and analysis Component 1 sampled an estimated 2800 interviewees at a baseline and each of two follow-ups from four Emergency Departments in Scotland and Northern England. Research nurses administered a standardised survey to assess alcohol consumption and the proportion of attendances that were alcohol-related.Component 2 covered six Sexual Health Clinics with similar timings and country allocation. A self-completion survey gathered information on potential unintended effects of MUP on alcohol source and drug use.Using a natural experiment design and repeated cross-sectional audit, difference between Scotland (intervention) and North England (control) will be tested for outcomes using regression adjusting for differences at baseline. Differential impacts by age, gender and socioeconomic position will be investigated.Component 3 used focus groups with young people and heavy drinkers and interviews with stakeholders before and after MUP implementation. The focus groups will allow exploration of attitudes, experiences and behaviours and the potential mechanisms by which impacts arise. The interviews will help characterise the implementation process.Ethics and dissemination Study components 1 and 2 have been ethically approved by the NHS, and component 3 by the University of Stirling. Dissemination plans include peer-reviewed journal articles, presentations, policy maker briefings and, in view of high public interest and the high political profile of this flagship policy, communication with the public via media engagement and plain language summaries

    Observation of an Excited Bc+ State

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    Using pp collision data corresponding to an integrated luminosity of 8.5 fb-1 recorded by the LHCb experiment at center-of-mass energies of s=7, 8, and 13 TeV, the observation of an excited Bc+ state in the Bc+Ο€+Ο€- invariant-mass spectrum is reported. The observed peak has a mass of 6841.2Β±0.6(stat)Β±0.1(syst)Β±0.8(Bc+) MeV/c2, where the last uncertainty is due to the limited knowledge of the Bc+ mass. It is consistent with expectations of the Bcβˆ—(2S31)+ state reconstructed without the low-energy photon from the Bcβˆ—(1S31)+β†’Bc+Ξ³ decay following Bcβˆ—(2S31)+β†’Bcβˆ—(1S31)+Ο€+Ο€-. A second state is seen with a global (local) statistical significance of 2.2Οƒ (3.2Οƒ) and a mass of 6872.1Β±1.3(stat)Β±0.1(syst)Β±0.8(Bc+) MeV/c2, and is consistent with the Bc(2S10)+ state. These mass measurements are the most precise to date

    Bose-Einstein correlations of same-sign charged pions in the forward region in pp collisions at √s=7 TeV

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    Bose-Einstein correlations of same-sign charged pions, produced in protonproton collisions at a 7 TeV centre-of-mass energy, are studied using a data sample collected by the LHCb experiment. The signature for Bose-Einstein correlations is observed in the form of an enhancement of pairs of like-sign charged pions with small four-momentum difference squared. The charged-particle multiplicity dependence of the Bose-Einstein correlation parameters describing the correlation strength and the size of the emitting source is investigated, determining both the correlation radius and the chaoticity parameter. The measured correlation radius is found to increase as a function of increasing charged-particle multiplicity, while the chaoticity parameter is seen to decreas

    Measurement of the inelastic pp cross-section at a centre-of-mass energy of 13TeV

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    The cross-section for inelastic proton-proton collisions at a centre-of-mass energy of 13TeV is measured with the LHCb detector. The fiducial cross-section for inelastic interactions producing at least one prompt long-lived charged particle with momentum p > 2 GeV/c in the pseudorapidity range 2 < Ξ· < 5 is determined to be Ο­ acc = 62:2 Β± 0:2 Β± 2:5mb. The first uncertainty is the intrinsic systematic uncertainty of the measurement, the second is due to the uncertainty on the integrated luminosity. The statistical uncertainty is negligible. Extrapolation to full phase space yields the total inelastic proton-proton cross-section Ο­ inel = 75:4 Β± 3:0 Β± 4:5mb, where the first uncertainty is experimental and the second due to the extrapolation. An updated value of the inelastic cross-section at a centre-of-mass energy of 7TeV is also reported

    New Mouse Lines for the Analysis of Neuronal Morphology Using CreER(T)/loxP-Directed Sparse Labeling

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    BACKGROUND: Pharmacologic control of Cre-mediated recombination using tamoxifen-dependent activation of a Cre-estrogen receptor ligand binding domain fusion protein [CreER(T)] is widely used to modify and/or visualize cells in the mouse. METHODS AND FINDINGS: We describe here two new mouse lines, constructed by gene targeting to the Rosa26 locus to facilitate Cre-mediated cell modification. These lines should prove particularly useful in the context of sparse labeling experiments. The R26rtTACreER line provides ubiquitous expression of CreER under transcriptional control by the tetracycline reverse transactivator (rtTA); dual control by doxycycline and tamoxifen provides an extended dynamic range of Cre-mediated recombination activity. The R26IAP line provides high efficiency Cre-mediated activation of human placental alkaline phosphatase (hPLAP), complementing the widely used, but low efficiency, Z/AP line. By crossing with mouse lines that direct cell-type specific CreER expression, the R26IAP line has been used to produce atlases of labeled cholinergic and catecholaminergic neurons in the mouse brain. The R26IAP line has also been used to visualize the full morphologies of retinal dopaminergic amacrine cells, among the largest neurons in the mammalian retina. CONCLUSIONS: The two new mouse lines described here expand the repertoire of genetically engineered mice available for controlled in vivo recombination and cell labeling using the Cre-lox system

    Stat1 Phosphorylation Determines Ras Oncogenicity by Regulating p27Kip1

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    Inactivation of p27Kip1 is implicated in tumorigenesis and has both prognostic and treatment-predictive values for many types of human cancer. The transcription factor Stat1 is essential for innate immunity and tumor immunosurveillance through its ability to act downstream of interferons. Herein, we demonstrate that Stat1 functions as a suppressor of Ras transformation independently of an interferon response. Inhibition of Ras transformation and tumorigenesis requires the phosphorylation of Stat1 at tyrosine 701 but is independent of Stat1 phosphorylation at serine 727. Stat1 induces p27Kip1 expression in Ras transformed cells at the transcriptional level through mechanisms that depend on Stat1 phosphorylation at tyrosine 701 and activation of Stat3. The tumor suppressor properties of Stat1 in Ras transformation are reversed by the inactivation of p27Kip1. Our work reveals a novel functional link between Stat1 and p27Kip1, which act in coordination to suppress the oncogenic properties of activated Ras. It also supports the notion that evaluation of Stat1 phosphorylation in human tumors may prove a reliable prognostic factor for patient outcome and a predictor of treatment response to anticancer therapies aimed at activating Stat1 and its downstream effectors

    Intended and unintended consequences of the implementation of minimum unit pricing of alcohol in Scotland: a natural experiment

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    Background: Scotland was the first country to implement minimum unit pricing for alcohol nationally. Minimum unit pricing aims to reduce alcohol-related harms and to narrow health inequalities. Minimum unit pricing sets a minimum retail price based on alcohol content, targeting products preferentially consumed by high-risk drinkers. This study comprised three components. Objectives: This study comprised three components assessing alcohol consumption and alcohol-related attendances in emergency departments, investigating potential unintended effects of minimum unit pricing on alcohol source and drug use, and exploring changes in public attitudes, experiences and norms towards minimum unit pricing and alcohol use. Design: We conducted a natural experiment study using repeated cross-sectional surveys comparing Scotland (intervention) and North England (control) areas. This involved comparing changes in Scotland following the introduction of minimum unit pricing with changes seen in the north of England over the same period. Difference-in-difference analyses compared intervention and control areas. Focus groups with young people and heavy drinkers, and interviews with professional stakeholders before and after minimum unit pricing implementation in Scotland allowed exploration of attitudes, experiences and behaviours, stakeholder perceptions and potential mechanisms of effect. Setting: Four emergency departments in Scotland and North England (component 1), six sexual health clinics in Scotland and North England (component 2), and focus groups and interviews in Scotland (component 3). Participants: Research nurses interviewed 23,455 adults in emergency departments, and 15,218 participants self-completed questionnaires in sexual health clinics. We interviewed 30 stakeholders and 105 individuals participated in focus groups. Intervention: Minimum unit pricing sets a minimum retail price based on alcohol content, targeting products preferentially consumed by high-risk drinkers. Results: The odds ratio for an alcohol-related emergency department attendance following minimum unit pricing was 1.14 (95% confidence interval 0.90 to 1.44; p = 0.272). In absolute terms, we estimated that minimum unit pricing was associated with 258 more alcohol-related emergency department visits (95% confidence interval –191 to 707) across Scotland than would have been the case had minimum unit pricing not been implemented. The odds ratio for illicit drug consumption following minimum unit pricing was 1.04 (95% confidence interval 0.88 to 1.24; p = 0.612). Concerns about harms, including crime and the use of other sources of alcohol, were generally not realised. Stakeholders and the public generally did not perceive price increases or changed consumption. A lack of understanding of the policy may have caused concerns about harms to dependent drinkers among participants from more deprived areas. Limitations: The short interval between policy announcement and implementation left limited time for pre-intervention data collection. Conclusions: Within the emergency departments, there was no evidence of a beneficial impact of minimum unit pricing. Implementation appeared to have been successful and there was no evidence of substitution from alcohol consumption to other drugs. Drinkers and stakeholders largely reported not noticing any change in price or consumption. The lack of effect observed in these settings in the short term, and the problem-free implementation, suggests that the price per unit set (Β£0.50) was acceptable, but may be too low. Our evaluation, which itself contains multiple components, is part of a wider programme co-ordinated by Public Health Scotland and the results should be understood in this wider context

    A VERITAS/Breakthrough Listen Search for Optical Technosignatures

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    The Breakthrough Listen Initiative is conducting a program using multiple telescopes around the world to search for "technosignatures": artificial transmitters of extraterrestrial origin from beyond our solar system. The VERITAS Collaboration joined this program in 2018, and provides the capability to search for one particular technosignature: optical pulses of a few nanoseconds duration detectable over interstellar distances. We report here on the analysis and results of dedicated VERITAS observations of Breakthrough Listen targets conducted in 2019 and 2020 and of archival VERITAS data collected since 2012. Thirty hours of dedicated observations of 136 targets and 249 archival observations of 140 targets were analyzed and did not reveal any signals consistent with a technosignature. The results are used to place limits on the fraction of stars hosting transmitting civilizations. We also discuss the minimum-pulse sensitivity of our observations and present VERITAS observations of CALIOP: a space-based pulsed laser onboard the CALIPSO satellite. The detection of these pulses with VERITAS, using the analysis techniques developed for our technosignature search, allows a test of our analysis efficiency and serves as an important proof-of-principle.Comment: 15 pages, 7 figure
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