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    Multi-isotopic study of the earliest medieval inhabitants of Santiago de Compostela (Galicia, Spain)

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    YesSantiago de Compostela is, together with Rome and Jerusalem, one of the three main pilgrimage and religious centres for Catholicism. The belief that the remains of St James the Great, one of the twelve apostles of Jesus Christ, is buried there has stimulated, since their reported discovery in the 9th century AD, a significant flow of people from across the European continent and beyond. Little is known about the practical experiences of people living within the city during its rise to prominence, however. Here, for the first time, we combine multi-isotope analysis (δ13C, δ15N, δ18Oap, δ13Cap, and 87Sr/86Sr) and radiocarbon dating (14C) of human remains discovered at the crypt of the Cathedral of Santiago to directly study changes in diet and mobility during the first three centuries of Santiago’s emergence as an urban centre (9th-12th centuries AD). Together with assessment of the existing archaeological data, our radiocarbon chronology broadly confirms historical tradition regarding the first occupation of the site. Isotopic analyses reveal that the foundation of the religious site attracted migrants from the wider region of the northwest corner of the Iberian Peninsula, and possibly from further afield. Stable isotope analysis of collagen, together with information on tomb typology and location, indicates that the inhabitants of the city experienced increasing socioeconomic diversity as it became wealthier as the hub of a wide network of pilgrimage. Our research represents the potential of multidisciplinary analyses to reveal insights into the origins and impacts of the emergence of early pilgrimage centres on the diets and status of communities within Christian medieval Europe and beyond.This project has been supported by a grant from the ‘la Caixa’ Banking Foundation (ID 100010434; Code: LCF/BQ/ES16/11570006). Patxi Pérez-Ramallo and Patrick Roberts would also like to thank the Max Planck Society for funding for this project. Patxi Pérez-Ramallo, Hannah Koon and Julia Beaumont would like to thank the University of Bradford for funding a support the first osteological and stable isotope analysis conducted in 2015. Two of the isotopic analyses and 14C dates have been carried out with funding from the Xunta de Galicia to the CulXeo Group (ED431B 2018/47) and to the research network ‘Cultural Heritage, archaeological and technical services’ (R2016/023). Open Access funding enabled and organized by Projekt DEAL

    Design and Operation of Multi Effect Distillation- Reverse Osmosis based Hybrid Desalination Process. Modelling, Simulation and Optimisation of Design and Operation Parameters of Multi Effect Distillation and Reverse Osmosis Hybrid Desalination Processes for Producing Multi-grade Waters at Minimum Energy and Minimum Cost of Production

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    The fast growth in the demand of freshwater due to the scarcity of natural water and increase in the world population puts more stress on the desalination sectors, which requires the installation of high-efficient thermal desalination plants. Among these desalination plants, multi effect desalination (MED) and RO processes are considered as the most reliable techniques of producing freshwater from saline water. Recently, the MED and RO process have been introduced in hybrid systems. However, this includes the development of simple superstructures of the hybrid system in spite of the improvement made beyond the individual process. To overcome this challenge, this dissertation comes to fill this gap and investigates appropriate methods of optimising the operational parameters of the hybrid system. In this regard, several innovative ideas are demonstrated for the first time to enhance the MED process, which are specifically include the improvement of key performance indicators including water production cost via a repetitive simulation based model. In line of this, the investigation of the lowest water production cost for different numbers of effects of MED system is carried out via optimisation based model. To deploy a sustainable source of energy, this research illustrates the combined system of MED-TVC and wind turbine with attaining a considerable reduction of specific energy consumption. Also, this research presents two novel designs of hybrid system of MED and single and double RO processes of different configurations that contain permeate reprocessing design and retentate reprocessing design of RO process. These layouts demonstrate a considerable reduction of total energy consumption within an accepted product salinity compared to the ones presented in the open literature. To apply the energy-water concept for a smart city, this research emphasises on the design moderation and process optimisation of the MED-TVC and double RO processes to generate different grades of water. Moreover, the structure of this dissertation introduces a revision of the steady state MED and RO modelling. This in turn provides an efficient hybrid system for seawater desalination by refining the reliability and efficiency of the associated process. The results stated the following findings; It can be stated that 17 effects of MED-TVC system is suitable to achieve the lowest fresh water production cost of 0.614 /m3.However,theimplicationofparticleswarmoptimisationmethodhasfurtherintroducedthefreshwaterproductioncostfrom0.614/m3. However, the implication of particle swarm optimisation method has further introduced the freshwater production cost from 0.614 /m3 to 0.432 $/m3 by investigating the optimal operating conditions for the 17 effects. Also, this research introduces that Dhahran is more potential compared to Jeddah in the KSA to construct an integration system of MED-TVC and a renewable energy source of wind turbine that presents the lowest specific energy consumption. This research also shows that the new proposed design of MED-TVC and single permeate reprocessing RO processes has a lower energy consumption of around 2.2% if compared to other configurations suggested in the open literature. Further reduction of this energy consumption has been conducted after optimising the inlet conditions of the hybrid system of MED-TVC and permeate reprocessing RO processes. The novel design of double RO and MED-TVC introduces an improvement of water productivity of 9%, corresponding to a reduction of brine flowrate within 5% compared to the base case of permeate reprocessing RO (PRRO) and MED-TVC. Finally, this research presents the improvement of different scenarios of MED-TVC and double RO processes to quantify the production of different types of water with fulfilling the environmental concepts

    Transformative role of big data through enabling capability recognition in construction

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    YesBig data application is a significant transformative driver of change in the retail, health, engineering, and advanced manufacturing sectors. Big data studies in construction are still somewhat limited, although there is increasing interest in what big data application could achieve. Through interviews with construction professionals, this paper identifies the capabilities needed in construction firms to enable the accrual of the potentially transformative benefits of big data application in construction. Based on previous studies, big data application capabilities, needed to transform construction processes, focussed on data, people, technology, and organisation. However, the findings of this research suggest a critical modification to that focus to include knowledge and the organisational environment along with people, data, and technology. The research findings show that construction firms use big data with a combination strategy to enable transformation by (a) driving an in-house data management policy to rolling-out the big data capabilities; (b) fostering collaborative capabilities with external firms for resource development, and (c) outsourcing big data services to address the capabilities deficits impacting digital transformation

    Proteomic Investigation of Endocrine Therapy Resistance in Breast Cancer Investigating the Molecular Mechanisms for SERM Resistant Cell Lines Using SILAC-Based Proteomic Approach

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    Introduction: Breast cancer is the second highest cause of cancer mortality in women worldwide. Hormonal therapy is considered one of the most effective therapies and is used against luminal-type malignancies. However, 40-50% of tumour cells can develop resistance, thereby limiting the success in breast cancer treatment. In this study, mechanisms of resistance were investigated using a novel multi-stable isotope labelled amino acids (SILAC) proteomics approach in phenotype-specific breast cancer cell lines resistant to endocrine treatment. Method: In vitro chemo-sensitivity (IC50) was determined for MCF7, T47D, MDA-MB-231, MDA-MB-468, MDA-MB-453, BT-20 and MCF-10A breast cell lines using four endocrine-based therapeutic agents (Tamoxifen, 4-Hydroxytamoxifen OHT, Raloxifene, Anastrozole) to select viable strains for resistance studies. MCF7 (luminal-type A) and MDA-MB-231 (triple negative breast cancer, TNBC) were selected and initially subject to OHT or raloxifene exposure with gradual increments for 10 months. WT cells were grown in the absence of drug in parallel as passage controls. Resistant cell lines were assessed by MTT and IF for comparison with parental cell lines. Resistant cell lines, along with the passage control and a SILAC control, were grown in “light” SILAC medium together with WT strains cultured in “heavy” SILAC medium. Proteins were extracted, concentrations determined and analysed by SDS PAGE for quality control. An aliquot of each “light” cell line (resistant, passage control or SILAC control) was combined with an equal amount of “heavy” WT, trypsin digested and analysed by nano-HPLC Orbitrap Fusion mass spectrometry (2D-LC MS/MS). Proteins were identified by database searching using MascotTM. Relative changes (resistant/WT ratio) in protein levels were determined and bioinformatics tools (STRING and UniProt) used to explore significantly changed pathways associated with resistance. Western blotting was used to verify selected target proteins. Results: Four consistently resistant sublines were generated MCF7 OHT Res (2.00-fold more resistant), MCF7 Ralx Res (2.00-fold), MDA-MB-231 OHT Res (1.90-fold change) and MDA-MB-231 Ralx Res (2.00-fold), in addition to two high passage controls. ER expression by IF was decreased in MCF7 OHT Res compared to the WT and MCF7 Ralx Res, whereas CD44 was increased. Proteomic analysis revealed 2247 and 2880 total proteins in MCF7 OHT Res and MCF7 Ralx Res whilst 3471 and 3495 total proteins were identified in MDA-MB-231 OHT Res and MDA-MB-231 Ralx Res, respectively. Bioinformatics tools identified significantly changed pathways included apoptosis, cytoskeleton, cell motility and redox cell homeostasis. Components of the MAPK-signalling cascade were consistently found to be upregulated in resistant cell lines. MAPK1 (ERK2), previously associated with tamoxifen resistance was increased in MDA-MB-231 Ralx Res cell lines by 4.45-fold and confirmed by Western blotting. Sorcin, which contributes to calcium homeostasis and is also linked to multidrug resistance was increased 4.11- and 2.35-fold in MCF7 OHT Res and Ralx Res sub cell lines, respectively. Some results, such as those for c-Jun, were inconsistent between proteomic analysis and Western blotting and require further investigation. Conclusion: The unique resistant cell lines generated here, as well the MCF7 OHT resistant line, provided novel data that give insights into the biological pathways involved in mechanisms of endocrine drug resistance in breast cancer. Proteomics analysis provided extensive data on common functionality and pathways across the resistant cell lines independent of phenotype or SERM. Overall, the results provided interesting targets for re-sensitising resistant breast cancer and the potential to investigate novel combination therapies in the future.Al-Ahliyya Amman University scholaship

    Planning and Operation of Hybrid AC-DC Microgird with High Penetration of Renewable Energy Sources

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    A hybrid ac/dc microgrid is a more complex but practical network that combines the advantages of an AC and a DC system. The main advantage of this network is that it connects both alternating current and direct current networks via an interlinking converter (IC) to form a unified distribution grid. The hybrid microgrid (HMG) will enable the direct integration of both alternating current (AC) and direct current (DC) distributed generators (DGs), energy storage systems (ESS), and alternating current and direct current (DC) loads into the grid. The alternating current and direct current sources, loads, and ESS are separated and connected to their respective subgrids primarily to reduce power conversion and thus increase overall system efficiency. As a result, the HMG architecture improves power quality and system reliability. Planning a hybrid microgrid entails estimating the capacities of DGs while taking technical, economic, and environmental factors into account. The hybrid ac-dc microgrid is regarded as the distribution network of the future, as it will benefit from both ac and dc microgrids. This thesis presents a general architecture of a hybrid ac-dc microgrid, which includes both planning and design. The goal of the Hybrid ac-dc microgrid planning problem is to maximise social welfare while minimising total planning costs such as investment, maintenance, and operation costs. This configuration will assist Hybrid microgrid planners in estimating planning costs while allowing them to consider any type of load ac/dc and DER type. Finally, this thesis identifies the research questions and proposes a future research plan

    Advancing cluster randomised trials in children's therapy: a survey of the acceptability of trial behaviours to therapists and parents

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    YesRandomised controlled trials of non-pharmacological interventions in children's therapy are rare. This is, in part, due to the challenges of the acceptability of common trial designs to therapists and service users. This study investigated the acceptability of participation in cluster randomised controlled trials to therapists and service users. A national electronic survey of UK occupational therapists, physiotherapists, speech and language therapists, service managers, and parents of children who use their services. Participants were recruited by NHS Trusts sharing a link to an online questionnaire with children's therapists in their Trust and with parents via Trust social media channels. National professional and parent networks also recruited to the survey. We aimed for a sample size of 325 therapists, 30 service managers, and 60 parents. Trial participation was operationalised as three behaviours undertaken by both therapists and parents: agreeing to take part in a trial, discussing a trial, and sharing information with a research team. Acceptability of the behaviours was measured using an online questionnaire based on the Theoretical Framework of Acceptability constructs: affective attitude, self-efficacy, and burden. The general acceptability of trials was measured using the acceptability constructs of intervention coherence and perceived effectiveness. Data were collected from June to September 2020. Numerical data were analysed using descriptive statistics and textual data by descriptive summary. A total of 345 survey responses were recorded. Following exclusions, 249 therapists and 40 parents provided data which was 69.6% (289/415) of the target sample size. It was not possible to track the number of people invited to take the survey nor those who viewed, but did not complete, the online questionnaire for calculation of response rates. A completion rate (participants who completed the last page of the survey divided by the participants who completed the first, mandatory, page of the survey) of 42.9% was achieved. Of the three specified trial behaviours, 140/249 (56.2%) therapists were least confident about agreeing to take part in a trial. Therapists (135/249, 52.6%) reported some confidence they could discuss a trial with a parent and child at an appointment. One hundred twenty of 249 (48.2%) therapists reported confidence in sharing information with a research team through questionnaires and interviews or sharing routine health data. Therapists (140/249, 56.2%) felt that taking part in the trial would take a lot of effort and resources. Support and resources, confidence with intervention allocation, and sense of control and professional autonomy over clinical practice were factors that positively affected the acceptability of trials. Of the 40 parents, twelve provided complete data. Most parents (18/40, 45%) agreed that it was clear how trials improve children's therapies and outcomes and that a cluster randomised trial made sense to them in their therapy situation (12/29, 30%). Using trials to evaluate therapy interventions is, in principle, acceptable to therapists, but their willingness to participate in trials is variable. The willingness to participate may be particularly influenced by their views related to the burden associated with trials, intervention allocation, and professional autonomy.The study was funded and supported by the UK Occupational Therapy Research Foundation, a division of the Royal College of Occupational Therapists, as part of the 2018–2021 Research Priority Grant

    Analyzing the perspectives of health professionals and legal cannabis users on the treatment of chronic pain with cannabidiol: A scoping review

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    YesMedical cannabis is one of the most commonly reported therapeutic treatments sought for chronic pain. The wide acceptance and research in alternative medicine has put medical cannabis in the limelight, where researchers are widely examining the therapeutic benefits of medical cannabis and its association to treat chronic pain. The purpose of this scoping review is to provide an overview of the perspectives on CBD as an alternative treatment for chronic pain among health professionals and legal cannabis users

    Assessing the impacts of creating active schools on organisational culture for physical activity

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    YesNational and international guidance recommends whole-school approaches to physical activity, but there are few studies assessing their effectiveness, especially at an organisational level. This study assesses the impact of the Creating Active School's (CAS) programme on organisational changes to physical activity provision. In-school CAS leads completed a 77-item questionnaire assessing school-level organisational change. The questionnaire comprised 19 domains aligned with the CAS framework and COM-B model of behaviour change. Wilcoxon Signed Rank Tests assessed the pre-to-nine-month change. >70% of schools (n = 53) pre-CAS had inadequate whole-school physical activity provision. After nine months (n = 32), CAS had a significant positive effect on organisational physical activity. The positive change was observed for: whole-school culture and ethos, teachers and wider school staff, academic lessons, physical education (PE) lessons, commute to/from school and stakeholder behaviour. This study provides preliminary evidence that CAS is a viable model to facilitate system-level change for physical activity in schools located within deprived areas of a multi-ethnic city. To confirm the results, future studies are required which adopt controlled designs combined with a holistic understanding of implementation determinants and underlying mechanisms.Z.E.H is funded via match funded PhD by the University of Bradford and Sport England Local Delivery Pilot Bradford. Authors, A.D-S and D.D.B. were supported by Sport England’s Local Delivery Pilot—Bradford. A.D-S and D.D.B were (also) supported by the Welcome Trust, a joint grant from the UK Medical Research Council (MRC) and UK Economic and Social Science Research Council a British Heart Foundation Clinical Study grant [CS/16/4/32482] the National Institute for Health Research under its Applied Research Collaboration Yorkshire and Humber [NIHR200166]; ActEarly UK Prevention Research Partnership Consortium [MR/S037527/1]; NIHR Clinical Research Network through research delivery support for this study

    Modeling and analysis of hybrid solar water desalination system for different scenarios in Indonesia

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    YesClean water demand has significantly increased due to the rise in the global population. However, most water on the Earth has high saline content that cannot be consumed directly; only about one over forty of the total water source is freshwater. Desalinated water is one of the potential solutions to meet the growing demand for freshwater, which is highly energy intensive. This paper analyses the energy, economic and environmental performance of a 5 m3/day PV (photovoltaic) powered reverse osmosis (RO) desalination system. Three scenarios of PV-RO with and without battery storage and diesel generator hybrid systems have been analyzed and investigated for the annual estimate load, net present value, and payback period of the water and electricity production costs. Also, the CO2 avoidance over the lifetime operation of all scearios is evaluated. This study shows that the PV-RO system without battery with 6.3 kW PV panels installed and with a 2-days water storage tank system is the most profitable economically f. For this scenario, the Levelized Cost of Electricity (LCOE), Levelized Cost of Water (LCOW), and Payback Period (PBP) are found to be 0.154/kWh,0.154/kWh, 0.627/m3, and five years, respectively. In addition, for this scenario, the CO2 emissions avoidance was the maximum (111,690 kg.CO2eq per year) compared to other scenarios

    How, for whom, and in what contexts will artificial intelligence be adopted in pathology? A realist interview study

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    YesThere is increasing interest in using artificial intelligence (AI) in pathology to improve accuracy and efficiency. Studies of clinicians' perceptions of AI have found only moderate acceptability, suggesting further research is needed regarding integration into clinical practice. This study aimed to explore stakeholders' theories concerning how and in what contexts AI is likely to become integrated into pathology. Materials and Methods: A literature review provided tentative theories that were revised through a realist interview study with 20 pathologists and 5 pathology trainees. Questions sought to elicit whether, and in what ways, the tentative theories fitted with interviewees' perceptions and experiences. Analysis focused on identifying the contextual factors that may support or constrain uptake of AI in pathology. Results: Interviews highlighted the importance of trust in AI, with interviewees emphasizing evaluation and the opportunity for pathologists to become familiar with AI as means for establishing trust. Interviewees expressed a desire to be involved in design and implementation of AI tools, to ensure such tools address pressing needs, but needs vary by subspecialty. Workflow integration is desired but whether AI tools should work automatically will vary according to the task and the context. Conclusions: It must not be assumed that AI tools that provide benefit in one subspecialty will provide benefit in others. Pathologists should be involved in the decision to introduce AI, with opportunity to assess strengths and weaknesses. Further research is needed concerning the evidence required to satisfy pathologists regarding the benefits of AI.This work was undertaken as part of the National Pathology Imaging Co-operative. National Pathology Imaging Co-operative, NPIC (Project no. 104687) is supported by a £50m investment from the Data to Early Diagnosis and Precision Medicine strand of the government’s Industrial Strategy Challenge Fund, managed and delivered by UK Research and Innovation (UKRI)

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