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Abstract Introduction ASCEND PLUS is a randomised controlled trial assessing the effects of oral semaglutide on the primary prevention of cardiovascular events in around 20,000 individuals with type 2 diabetes in the UK. The trial’s innovative design includes a decentralised direct-to-participant invitation, recruitment, and follow-up model, relying on self-completion of online forms or telephone or video calls with research nurses, with no physical sites. Extensive patient and public involvement and engagement (PPIE) was essential to the design and conduct of ASCEND PLUS. Aim To report the process and conduct of PPIE activity in ASCEND PLUS, evaluate effects on trial design, reflect critically on successes and aspects that could have been improved, and identify themes and learning relevant to implementation of PPIE in future trials. Methods PPIE activity was coordinated centrally and included six PPIE focus groups and creation of an ASCEND PLUS public advisory group (PAG) during the design phase. Recruitment to these groups was carefully considered to ensure diversity and inclusion, largely consisting of adults living with type 2 diabetes from across the UK. Two members of the PAG also joined the trial Steering Committee. Steering Committee meetings, focus groups, and PAG meetings were conducted online, with two hybrid workshops to discuss PPIE activity and aspects of the trial. Results PPIE activity was critical to shaping the design and conduct of ASCEND PLUS. Key examples included supporting choice for participants to either complete the screening/consent process independently online, or during a telephone or video call interview with a research nurse. A concise ‘initial information leaflet’ was developed to be sent with the initial invitations, with the ‘full’ information leaflet sent later to those interested in joining the trial. The PAG reviewed the content and format of participant- and public-facing materials, including written documents, online screening forms, animated videos, and the trial website, to aid clarity and accessibility, and provided input into the choice of instruments to assess quality of life. Conclusions PPIE is integral in ASCEND PLUS and will continue throughout the trial. This involvement has been critical to optimising the trial design, successfully obtaining regulatory and ethical approval, and conducting the trial.

COVID-19 is a novel virus that has spread globally, and governments around the world often implement different strategies to prevent its spread. In the literature, several COVID-19 models have been studied with the bilinear incident rate. In this study, the S1V1E1I1Q1R1 (susceptible-vaccinated-exposed-infective-quarantined-recovered) COVID-19 model is proposed. To investigate how the disease spreads in the population, an algorithm is used. The efficacy of the algorithm is used to calculate the disease-free equilibrium point. A next generation matrix technique is used to find R0. Furthermore, to check the effect of parameters on the basic reproduction number (R0), the sensitivity analysis is conducted. Numerical simulation displays that the disease spreads in the population by increasing the value of the contact rate β while the disease spread in the population reduces by increasing the value of the vaccination rate θ, quarantine rate ϕ, and recovery rate γ. Different optimal control strategies, such as social distance and quick isolation, are also implemented.

Objective Living Library events involve people being trained as living ‘Books’, who then discuss aspects of their personal experiences in direct conversation with attendees, referred to as ‘Readers’. This study sought to generate a realist programme theory and a theory-informed implementation guide for a Library of Lived Experience for Mental Health (LoLEM).Design Integrated realist synthesis and experience-based co-design.Setting Ten online workshops with participants based in the North of England.Participants Thirty-one participants with a combination of personal experience of using mental health services, caring for someone with mental health difficulties and/or working in mental health support roles.Results Database searches identified 30 published and grey literature evidence sources which were integrated with data from 10 online co-design workshops conducted over 12 months. The analysis generated a programme theory comprising five context-mechanism-outcome (CMO) configurations. Findings highlight how establishing psychological safety is foundational to productive Living Library events (CMO 1). For Readers, direct conversations humanise others’ experiences (CMO 2) and provide the opportunity to flexibly explore new ways of living (CMO 3). Through participation in a Living Library, Books may experience personal empowerment (CMO 4), while the process of self-authoring and co-editing their story (CMO 5) can contribute to personal development. This programme theory informed the co-design of an implementation guide highlighting the importance of tailoring event design and participant support to the contexts in which LoLEM events are held.Conclusions The LoLEM has appeal across stakeholder groups and can be applied flexibly in a range of mental health-related settings. Implementation and evaluation are required to better understand the positive and negative impacts on Books and Readers.Trial registration number PROSPERO CRD42022312789.

Introduction People with lived expertise in managing mental health challenges can be an important source of knowledge and support for other people facing similar challenges, and for carers to learn how best to help. However, opportunities for sharing lived expertise are limited. Living libraries support people with lived expertise to be ‘living books’, sharing their experiences in dialogue with ‘readers’ who can ask questions. Living libraries have been piloted worldwide in health-related contexts but without a clear model of how they work or rigorous evaluation of their impacts. We aim to develop a programme theory about how a living library could be used to improve mental health outcomes, using this theory to codesign an implementation guide that can be evaluated across different contexts.Methods and analysis We will use a novel integration of realist synthesis and experience-based codesign (EBCD) to produce a programme theory about how living libraries work and a theory and experience informed guide to establishing a library of lived experience for mental health (LoLEM). Two workstreams will run concurrently: (1) a realist synthesis of literature on living libraries, combined with stakeholder interviews, will produce several programme theories; theories will be developed collaboratively with an expert advisory group of stakeholders who have hosted or taken part in a living library and will form our initial analysis framework; a systematic search will identify literature about living libraries; data will be coded into our analysis framework, and we will use retroductive reasoning to explain living libraries’ impacts across multiple contexts. Individual stakeholder interviews will help refine and test theories; (2) data from workstream 1 will inform 10 EBCD workshops with people with experience of managing mental health difficulties and health professionals to produce a LoLEM implementation guide; data from this process will also inform the theory in workstream 1.Ethics and dissemination Ethical approval was granted by Coventry and Warwick National Health Service Research Ethics Committee on 29 December 2021 (reference number 305975). The programme theory and implementation guide will be published as open access and shared widely through a knowledge exchange event, a study website, mental health provider and peer support networks, peer reviewed journals and a funders report.PROSPERO registration details CRD42022312789.

The present study aims to investigate the Casson nanofluids flow theoretically over a vertical Riga plate. The temperature and concentration with ramped and isothermal wall conditions are considered. Moreover, the fluid is considered electrically conducted. Concrete is considered as a base fluid while clay nanoparticles are added to it. The present flow regime is formulated in terms of a system of partial differential equations. Using dimensionless variables, the system of equations with the imposed boundary conditions is non-dimensionalized. The Laplace transform technique is used to calculate the exact solutions for the temperature, concentration, and velocity distributions. The effect of various embedded parameters on the velocity, temperature, and concentration fields are shown graphically and discussed physically. The variation in the skin friction for various values of clay nanoparticles volume fraction is shown in tabular form. The results indicate that adding 4% clay nanoparticles, enhanced the skin friction up to 7.04% in instance of ramped wall temperature (RWT) and 11.13% in isothermal wall temperature (IWT). This result is worth noting because the increase in skin friction causes rapid compaction of the cementitious materials and improves the tensile strength of the concrete.

In this paper, for the first time, we investigate the relationship between infrastructure and sectoral distribution of FDI inflow in China. We use the Estimating Autoregressive Distributed Lag (ARDL) bound testing and Vector Error Correction Model (VECM) procedures of estimation. To unmask the shortcomings in the previous literature, we use a composite index of infrastructure with more than 30 indicators. The results show that there is a long-run relationship between sectoral FDI and infrastructure. A bidirectional causal relationship is confirmed by using VECM. However, we find unidirectional causality between the primary sector's FDI and infrastructure, and it is running from infrastructure to primary sector FDI. The inclusion of control variables, e.g., institutional quality, trade openness, and domestic investment, is robust in our analysis. The positive role of infrastructure in the sectoral distribution of FDI inflows is of utmost importance for policymakers and Chinese-government. Several policy implications are given in our study.

This study seeks to investigate theimpactof China’sexchange rate onthe trade balance of 41 Sub‑aharan African countries for the period from 1994 to 2016. Using an augmented gravity model, the grouped and ungrouped results of the study confirm the elasticity and absorption approaches of the trade balance. Similarly, the robustness check, by dividing the sample period into two sub‑eriods (2005–016 and 1994–004), also confirms the elasticity and absorption approaches of the trade balance.

Background: For people in mental health crisis, acute day units provide daily structured sessions and peer support in non-residential settings as an alternative to crisis resolution teams. Objectives: To investigate the provision, effectiveness, intervention acceptability and re-admission rates of acute day units. Design: Work package 1 – mapping and national questionnaire survey of acute day units. Work package 2.1 – cohort study comparing outcomes during a 6-month period between acute day unit and crisis resolution team participants. Work package 2.2 – qualitative interviews with staff and service users of acute day units. Work package 3 – a cohort study within the Mental Health Minimum Data Set exploring re-admissions to acute care over 6 months. A patient and public involvement group supported the study throughout. Setting and participants: Work package 1 – all non-residential acute day units (NHS and voluntary sector) in England. Work packages 2.1 and 2.2 – four NHS trusts with staff, service users and carers in acute day units and crisis resolution teams. Work package 3 – all individuals using mental health NHS trusts in England. Results: Work package 1 – we identified 27 acute day units in 17 out of 58 trusts. Acute day units are typically available on weekdays from 10 a.m. to 4 p.m., providing a wide range of interventions and a multidisciplinary team, including clinicians, and having an average attendance of 5 weeks. Work package 2.1 – we recruited 744 participants (acute day units, n = 431; crisis resolution teams, n = 312). In the primary analysis, 21% of acute day unit participants (vs. 23% of crisis resolution team participants) were re-admitted to acute mental health services over 6 months. There was no statistically significant difference in the fully adjusted model (acute day unit hazard ratio 0.78, 95% confidence interval 0.54 to 1.14; p = 0.20), with highly heterogeneous results between trusts. Acute day unit participants had higher satisfaction and well-being scores and lower depression scores than crisis resolution team participants. The health economics analysis found no difference in resource use or cost between the acute day unit and crisis resolution team groups in the fully adjusted analysis. Work package 2.2 – 36 people were interviewed (acute day unit staff, n = 12; service users, n = 21; carers, n = 3). There was an overwhelming consensus that acute day units are highly valued. Service users found the high amount of contact time and staff continuity, peer support and structure provided by acute day units particularly beneficial. Staff also valued providing continuity, building strong therapeutic relationships and providing a variety of flexible, personalised support. Work package 3 – of 231,998 individuals discharged from acute care (crisis resolution team, acute day unit or inpatient ward), 21.4% were re-admitted for acute treatment within 6 months, with women, single people, people of mixed or black ethnicity, those living in more deprived areas and those in the severe psychosis care cluster being more likely to be re-admitted. Little variation in re-admissions was explained at the trust level, or between trusts with and trusts without acute day units (adjusted odds ratio 0.96, 95% confidence interval 0.80 to 1.15). Limitations: In work package 1, some of the information is likely to be incomplete as a result of trusts’ self-reporting. There may have been recruitment bias in work packages 2.1 and 2.2. Part of the health economics analysis relied on clinical Health of the Nations Outcome Scale ratings. The Mental Health Minimum Data Set did not contain a variable identifying acute day units, and some covariates had a considerable number of missing data. Conclusions: Acute day units are not provided routinely in the NHS but are highly valued by staff and service users, giving better outcomes in terms of satisfaction, well-being and depression than, and no significant differences in risk of re-admission or increased costs from, crisis resolution teams. Future work should investigate wider health and care system structures and the place of acute day units within them; the development of a model of best practice for acute day units; and staff turnover and well-being (including the impacts of these on care). Funding: This project was funded by the National Institute for Health Research (NIHR) Health Services and Delivery Research programme and will be published in full in Health Services and Delivery Research; Vol. 9, No. 18. See the NIHR Journals Library website for further project information.

One of the goals of developing a transport corridor is to promote socio-economic development by improving connectivity and sustainable transport operations, which largely depends on the operational strategy. Trade-off policies can be important tools for gaining the competitive advantage of road transport corridors, and thus, help facilitate sustainable growth and welfare. This article uses a case-based approach to observe the trade-offs in the first phase of transport infrastructure development, and then, in the second stage, further explores the trade-off variables in the transport operations strategy under the China-Pakistan Economic Corridor (CPEC). The results from the three cases of the parallel route system of the CPEC indicate that trade-off is an easily understandable and applicable method, which can foresee the operational gains or compromises for significant welfare of the regions. The implications of the trade-off are two fold, first is the “importance” of the trade-off, which is related to its impact on operational competitiveness. The other is the “sensitivity” of the trade-off, in terms of the change that will be caused to one variable when changing the other. The trade-off concept can be used for several landlocked transport corridors to achieve a competitive edge in transit trade.

China’s huge investment in the “belt and road initiative” (BRI) may have helped improve the economic level of participating countries, but it may also be accompanied by a substantial increase in greenhouse gas (GHG) emissions. The BRI corridors aim to bring regional stability and prosperity. In such efforts, energy efficiency due to increased transport has been overlooked in the recent literature. This paper employed a data envelopment analysis of the slack-based measurement (SBM) for bad output to assess the transport energy efficiency of 19 countries under the BRI economic corridors. By using the most cited transport-related input variables, such as vehicles, labor, motor oil, jet fuel, and natural gas, this study first analyzes the transport energy efficiency by first assuming the output variables individually and then takes two years as a pre- and post-BRI case by considering the aggregated output model. The results show an increase in economic activity but a decline in transport energy efficiency in terms of consumption and emissions.

The manuscript is a presentation of the combined effect of magnetic and electric field on unsteady flow of Maxwell nanofluid over a stretching surface with thermal radiations. The flow of Maxwell nanofluid is assumed to be in an unsteady state. The basic governing equations changed to a group of differential equations, using proper similarity variables. The obtained modeled equations are nonlinear and coupled. An optimal approach is used to acquire the solution of the modeled problem analytically. The effects of electric field, magnetic field and thermal radiations on Maxwell nanofluid are the main focus in this study. The impact of the Skin friction on velocity profile, Nusselt number on temperature profile and Sherwood number on concentration profile are studied numerically. The influential behavior of the unsteady parameter λ , magnetic parameter M , electric parameter E , radiation parameter R d , Maxwell parameter β , thermophoresis parameter N t , Prandtl number Pr , Schmidt number S c , space dependent coefficient A and temperature dependent coefficient B on the velocity f ( h ) , concentration ϕ ( η ) and temperature θ ( η ) are analyzed and studied. The consequences are drawn graphically to see the physical significance of the problem.

Bacteria, plants, and algae produce isoprenoids through the methylerythritol phosphate (MEP) pathway, an attractive pathway for antimicrobial drug development as it is present in prokaryotes and some lower eukaryotes but absent from human cells. The first committed step of the MEP pathway is catalyzed by 1-deoxy-D-xylulose 5-phosphate reductoisomerase (DXR/MEP synthase). MEP pathway genes have been identified in many biothreat agents, including Francisella, Brucella, Bacillus, Burkholderia, and Yersinia. The importance of the MEP pathway to Francisella is demonstrated by the fact that MEP pathway mutations are lethal. We have previously established that fosmidomycin inhibits purified MEP synthase (DXR) from F. tularensis LVS. FR900098, the acetyl derivative of fosmidomycin, was found to inhibit the activity of purified DXR from F. tularensis LVS (IC(50)=230 nM). Fosmidomycin and FR900098 are effective against purified DXR from Mycobacterium tuberculosis as well, but have no effect on whole cells because the compounds are too polar to penetrate the thick cell wall. Fosmidomycin requires the GlpT transporter to enter cells, and this is absent in some pathogens, including M. tuberculosis. In this study, we have identified the GlpT homologs in F. novicida and tested transposon insertion mutants of glpT. We showed that FR900098 also requires GlpT for full activity against F. novicida. Thus, we synthesized several FR900098 prodrugs that have lipophilic groups to facilitate their passage through the bacterial cell wall and bypass the requirement for the GlpT transporter. One compound, that we termed "compound 1," was found to have GlpT-independent antimicrobial activity. We tested the ability of this best performing prodrug to inhibit F. novicida intracellular infection of eukaryotic cell lines and the caterpillar Galleria mellonella as an in vivo infection model. As a lipophilic GlpT-independent DXR inhibitor, compound 1 has the potential to be a broad-spectrum antibiotic, and should be effective against most MEP-dependent organisms.