Quantifying the link between magma ascent dynamics and tilt

Magma viscosity and its ascent rate are key factors in controlling eruption style. Shear stress exerted on the conduit walls as magma ascends pulls up the surrounding edifice, whilst overpressure pushes the edifice outwards. Magma fractures if shear stress exceeds its shear strength, triggering low-frequency seismicity. Shear stress is proportional to both the viscosity of magma and its ascent velocity. Hence, it provides an important link between ascent dynamics and both deformation and seismicity that can be recorded at the surface. Tiltmeters measure changes in inclination, and both shear stress and pressure have been linked conceptually to changes in tilt recorded close to the conduit. However, how much shear stress and pressure are produced as magma ascends, and the relative contribution of each to the tilt, has not previously been quantified. Firstly, flow and deformation modelling are combined using COMSOL Multiphysics to quantitatively link magma ascent and tilt. Despite shear stress being several orders of magnitude smaller than overpressure at most depths, shear stress generally dominates the tilt signal. Next, I systematically investigate how topography influences tilt, showing how topography controls both the amplitude and polarity of the tilt, and thus the relative contribution of shear stress and pressure. 3D deformation modelling is performed including real volcanic topography to show how a tiltmeter can be strategically deployed at the location most sensitive to changes in source stress. Finally, time-dependent flow modelling is used to show how magma ascent dynamics, and thus shear stress and overpressure, evolve through time due to transient volcanic processes. The growth of a lava dome exerts an increasing loading pressure at the conduit vent that impedes magma ascent, and can cause it to stall even if conditions at depth remain unchanged. By unloading, a full or partial dome collapse can therefore cause an eruption to recommence. By quantitatively linking magma ascent and deformation, and examining how ascent evolves through time, this work shows the importance of combining flow and deformation modelling in retrospectively investigating what drives temporal variations in seismicity and deformation. This is an important step towards being able to develop a combined forecasting tool using both seismicity and deformation that can be used to detect critical changes in ascent dynamics

A Methodological Synthesis of Self-Paced Reading in Second Language Research : Methodological synthesis of SPR tests

Self-paced reading tests (SPRs) are being increasingly adopted by second language (L2) researchers. Using SPR with L2 populations presents specific challenges, and its use is still evolving in L2 research (as well as in first language research, in many respects). Although the topic of several narrative overviews (Keating & Jegerski, 2015; Roberts, 2016), we do not have a comprehensive picture of its usage in L2 research. Building on the growing body of systematic reviews of research practices in applied linguistics (e.g., Liu & Brown, 2015; Plonsky, 2013), we report a methodological synthesis of the rationales, study contexts, and methodological decision making in L2 SPR research. Our comprehensive search yielded 74 SPRs used in L2 research. Each instrument was coded along 121 parameters, including: reported rationales and study characteristics, indicating the scope and nature of L2 SPR research agendas; design and analysis features and reporting practices, determining instrument validity and reliability; and materials transparency, affecting reproducibility and systematicity of agendas. Our findings indicate an urgent need to standardize the use and reporting of this technique, requiring empirical investigation to inform methodological decision making. We also identify several areas (e.g., study design, sample demographics, instrument construction, data analysis, and transparency) where SPR research could be improved to enrich our understanding of L2 processing, reading, and learning

Experience and response to a randomised controlled trial of extended-release injectable buprenorphine versus sublingual tablet buprenorphine and oral liquid methadone for opioid use disorder:protocol for a mixed-methods evaluation

INTRODUCTION: Opioid use disorder (OUD) is a debilitating and persistent disorder. The standard-of-care treatment is daily maintenance dosing of sublingual buprenorphine (BUP-SL) or oral methadone (MET). Monthly, extended-release, subcutaneous injectable buprenorphine (BUP-XR) has been developed to enhance treatment effectiveness. This study aims to investigate the experiences of participants who have been offered BUP-XR (evaluation 1), health-related quality-of-life among participants who have opted to receive BUP-XR longer term (evaluation 2) and the experiences of participants allocated to receive BUP-XR or BUP-SL or MET with the offer of adjunctive personalised psychosocial intervention (evaluation 3). METHODS AND ANALYSIS: Three qualitative–quantitative (mixed-methods) evaluations embedded in a five-centre, head-to-head, randomised controlled trial of BUP-XR versus BUP-SL and MET in the UK. Evaluation 1 is a four-centre interview anchored on an OUD-related topic guide and conducted after the 24-week trial endpoint. Evaluation 2 is a two-centre interview anchored on medications for opioid use disorder-specific quality-of-life topic guide conducted among participants after 12–24 months. Evaluation 3: single-centre interview after the 24-week trial endpoint. All evaluations include selected trial clinical measures, with evaluation 2 incorporating additional questionnaires. Target participant recruitment for evaluations 1 and 2 is 15 participants per centre (n=60 and n=30, respectively). Recruitment for evaluation 3 is 15 participants per treatment arm (n=30). Each evaluation will be underpinned by theory, drawing on constructs from the behavioural model for health service use or the health-related quality-of-life model. Qualitative data analysis will be by iterative categorisation. ETHICS AND DISSEMINATION: Study protocol, consent materials and questionnaires were approved by the London-Brighton and Sussex research ethics committee (reference: 19/LO/0483) and the Health Research Authority (IRAS project number 255522). Participants will be provided with information sheets and informed written consent will be obtained for each evaluation. Study findings will be disseminated through peer-reviewed scientific journals. TRIAL REGISTRATION NUMBER: 2018-004460-63

A new fireworm (Amphinomidae) from the Cretaceous of Lebanon identified from three-dimensionally preserved myoanatomy

© 2015 Parry et al. Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. The attached file is the published version of the article

Superiority and cost-effectiveness of monthly extended-release buprenorphine versus daily standard of care medication: a pragmatic, parallel-group, open-label, multicentre, randomised, controlled, phase 3 trial

BACKGROUND: Daily methadone maintenance or buprenorphine treatment is the standard-of-care (SoC) medication for opioid use disorder (OUD). Subcutaneously injected, extended-release buprenorphine (BUP-XR) may be more effective-but there has been no superiority evaluation.METHODS: This pragmatic, parallel-group, open-label, multi-centre, effectiveness superiority randomised, controlled, phase 3 trial was conducted at five National Health Service community-based treatment clinics in England and Scotland. Participants (adults aged ≥ 18 years; all meeting DSM-5 diagnostic criteria for moderate or severe OUD at admission to their current maintenance treatment episode) were randomly assigned (1:1) to receive continued daily SoC (liquid methadone (usual dose range: 60-120 mg) or sublingual/transmucosal buprenorphine (usual dose range: 8-24 mg) for 24 weeks; or monthly BUP-XR (Sublocade;® two injections of 300 mg, then four maintenance injections of 100 mg or 300 mg, with maintenance dose selected by response and preference) for 24 weeks. In the intent-to-treat population (senior statistician blinded to blinded to treatment group allocation), and with a seven-day grace period after randomisation, the primary endpoint was the count of days abstinent from non-medical opioids between days 8-168 (i.e., weeks 2-24; range: 0-161 days). Safety was reported for the intention-to- treat population. Adopting a broad societal perspective inclusive of criminal justice, NHS and personal social service costs, a trial-based cost-utility analysis estimated the Incremental Cost-effectiveness Ratio (ICER) per quality-adjusted life year (QALY) of BUP-XR versus SoC at the National Institute for Health and Care Excellence threshold. The study was registered EudraCT (2018-004460-63) and ClinicalTrials.gov (NCT05164549), and is completed.FINDINGS: Between Aug 9, 2019 and Nov 2, 2021, 314 participants were randomly allocated to receive SoC (n = 156) or BUP-XR (n = 158). Participants were abstinent from opioids for an adjusted mean of 104.37 days (standard error [SE] 9.89; range: 0-161 days) in the SoC group and an adjusted mean of 123.43 days (SE 4.76; range: 24-161 days) in the BUP-XR group (adjusted incident rate ratio [IRR] 1.18, 95% confidence interval [CI] 1.05-1.33; p-value 0.004). The incidence of any adverse event was higher in the BUP-XR group than the SoC group (128 [81.0%] of 158 participants versus 67 [42.9%] of 156 participants, respectively-most commonly rapidly-resolving (mild-moderate range) pain from drug administration in the BUP-XR group (121 [26.9%] of 450 adverse events). There were 11 serious adverse events (7.0%) in the 158 participants in the BUP-XR group, and 18 serious adverse events (11.5%) in the 156 participants in the SoC group-none judged to be related to study treatment. The BUP-XR treatment group had a mean incremental cost of £1033 (95% central range [CR] -1189 to 3225) and was associated with a mean incremental QALY of 0.02 (95% CR 0.00-0.05), and an ICER of £47,540 (0.37 probability of being cost-effective at the £30,000/QALY gained willingness-to-pay threshold). However, BUP-XR dominated the SoC among participants who were rated more severe at study baseline, and among participants in maintenance treatment for more that 28 days at study enrolment.INTERPRETATION: Evaluated against the daily oral SoC, monthly BUP-XR is clinically superior, delivering greater abstinence from opioids, and with a comparable safety profile. BUP-XR was not cost-effective in a base case cost-utility analysis using the societal perspective, but it was more effective and less costly (dominant) among participants with more severe OUD, or those whose current treatment episode was longer than 28 days. Further trials are needed to evaluate if BUP-XR is associated with better clinical and health economic outcomes over the longer term.FUNDING: Indivior.</p

Extended-release pharmacotherapy for opioid use disorder (EXPO):protocol for an open-label randomised controlled trial of the effectiveness and cost-effectiveness of injectable buprenorphine versus sublingual tablet buprenorphine and oral liquid methadone

BACKGROUND: Sublingual tablet buprenorphine (BUP-SL) and oral liquid methadone (MET) are the daily, standard-of-care (SOC) opioid agonist treatment medications for opioid use disorder (OUD). A sizable proportion of the OUD treatment population is not exposed to sufficient treatment to attain the desired clinical benefit. Two promising therapeutic technologies address this deficit: long-acting injectable buprenorphine and personalised psychosocial interventions (PSI). This study will determine (A) the effectiveness and cost-effectiveness — monthly injectable, extended-release (BUP-XR) in a head-to-head comparison with BUP-SL and MET, and (B) the effectiveness of BUP-XR with adjunctive PSI versus BUP-SL and MET with PSI. Safety, retention, craving, substance use, quality-adjusted life years, social functioning, and subjective recovery from OUD will be also evaluated. METHODS: This is a pragmatic, multi-centre, open-label, parallel-group, superiority RCT, with a qualitative (mixed-methods) evaluation. The study population is adults. The setting is five National Health Service community treatment centres in England and Scotland. At each centre, participants will be randomly allocated (1:1) to BUP-XR or SOC. At the London study co-ordinating centre, there will also be allocation of participants to BUP-XR with PSI or SOC with PSI. With 24 weeks of study treatment, the primary outcome is days of abstinence from non-medical opioids during study weeks 2–24 combined with up to 12 urine drug screen tests for opioids. For 90% power (alpha, 5%; 15% inflation for attrition), 304 participants are needed for the BUP-XR versus SOC comparison. With the same planning parameters, 300 participants are needed for the BUP-XR and PSI versus SOC and PSI comparison. Statistical and health economic analysis plans will be published before data-lock on the Open Science Framework. Findings will be reported in accordance with the Consolidated Standards of Reporting Trials and Consolidated Health Economic Evaluation Reporting Standards. DISCUSSION: This pragmatic randomised controlled trial is the first evaluation of injectable BUP-XR versus the SOC medications BUP-SL and MET, with personalised PSI. If there is evidence for the superiority of BUP-XR over SOC medication, study findings will have substantial implications for OUD clinical practice and treatment policy in the UK and elsewhere. TRIAL REGISTRATION: EU Clinical Trials register 2018-004460-63. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13063-022-06595-0

Use of contingency management incentives to improve completion of hepatitis B vaccination in people undergoing treatment for heroin dependence: a cluster randomised trial

Background: Poor adherence to treatment diminishes its individual and public health benefit. Financial incentives, provided on the condition of treatment attendance, could address this problem. Injecting drug users are a high-risk group for hepatitis B virus (HBV) infection and transmission, but adherence to vaccination programmes is poor. We aimed to assess whether contingency management delivered in routine clinical practice increased the completion of HBV vaccination in individuals receiving opioid substitution therapy. Methods: In our cluster randomised controlled trial, we enrolled participants at 12 National Health Service drug treatment services in the UK that provided opioid substitution therapy and nurse-led HBV vaccination with a super-accelerated schedule (vaccination days 0, 7, and 21). Clusters were randomly allocated 1:1:1 to provide vaccination without incentive (treatment as usual), with fixed value contingency management (three £10 vouchers), or escalating value contingency management (£5, £10, and £15 vouchers). Both contingency management schedules rewarded on-time attendance at appointments. The primary outcome was completion of clinically appropriate HBV vaccination within 28 days. We also did sensitivity analyses that examined vaccination completion with full adherence to appointment times and within a 3 month window. The trial is registered with Current Controlled Trials, number ISRCTN72794493. Findings: Between March 16, 2011, and April 26, 2012, we enrolled 210 eligible participants. Compared with six (9%) of 67 participants treated as usual, 35 (45%) of 78 participants in the fixed value contingency management group met the primary outcome measure (odds ratio 12·1, 95% CI 3·7–39·9; p<0·0001), as did 32 (49%) of 65 participants in the escalating value contingency management group (14·0, 4·2–46·2; p<0·0001). These differences remained significant with sensitivity analyses. Interpretation: Modest financial incentives delivered in routine clinical practice significantly improve adherence to, and completion of, HBV vaccination programmes in patients receiving opioid substitution therapy. Achievement of this improvement in routine clinical practice should now prompt actual implementation. Drug treatment providers should employ contingency management to promote adherence to vaccination programmes. The effectiveness of routine use of contingency management to achieve long-term behaviour change remains unknown

Virtual reconnection: The online spaces of alternative food networks in England

AbstractSpaces of ‘alternative’ food production and consumption have been the subject of considerable interest within agri-food research and policy-making circles in recent decades. Examples of these Alternative Food Networks (AFNs) include Farmers' Markets, Community Supported Agriculture (CSA) schemes and farm shops, where food products are embedded with social and spatial information that serves to differentiate them from conventional agri-food systems. These shorter, more transparent, localised supply chains that characterise AFNs are underpinned by the notion of reconnection – a fundamental set of biological, social and moral processes that enable agri-food stakeholders to participate in ethically minded, transparent systems, where they are better connected to one another and to the markets and environments in which they are immersed. Drawing on a range of eight AFN case studies in England and using a multi-method approach, we explore the notion of reconnection within online space to show how social relations have changed, and are changing as a result of online activity. In examining the websites and social media platforms of AFNs and primary data collected from the creators and users of these spaces, we uncover the notion of ‘virtual reconnection’. We found the embodied, socio-material reconnection processes that occur in-place also occur online. However, by extending AFN spaces, virtual reconnection cannot fully replicate the same embodied and tactile experiences associated with the material spaces of AFNs. As such, online spaces in the context of AFNs provide a useful additional realm for reconnection, but need to be understood as supplementary rather than as a substitution for socio-material reconnections. Future research should consider the moral dimensions of reconnection and the capacity that online spaces have for enhancing the inclusivity of Civic Food Networks (CFNs), and their transformative role in contributing to more sustainable behaviours