Now showing items 1-20 of 10770

    • Synthesis and biological evaluation of MMP-activated anti-cancer prodrugs

      Falconer, Robert A.; Loadman, Paul; Banisalman, Katreen A.F. (University of BradfordFaculty of Life Sciences, 2021)
    • Food Waste Reduction through Food Sharing Initiatives: The lived Experiences of Restaurants and Food Bank Employees in Riyadh

      Sharif, Amir M.; Sivarajah, Uthayasankar; Eldabi, Tillal; Abdur-Rahim, Abdulwasih I. (University of BradfordSchool of Management. Faculty of Management, Law, and Social Sciences, 2023)
      Today’s world is characterised by considerable inconsistency. In some parts of the world people are living in starvation and malnutrition, while in some other parts of the same world, about 1.3 billion tons of food is wasted every year. We do not know enough about what contributes to food waste. However, there seems to be an emergent pattern of behaviour around sharing food. This hermeneutic phenomenological research will explore how food sharing might reduce food waste in a cultural and community-based society like Saudi Arabia through the lived experiences of restaurants and food bank employees. Research data were collected through a face-to-face semi-structured interview method from 15 participants from selected restaurants and food bank in Riyadh. Using the theory of planned behaviour (TPB) as the theoretical lens, a conceptual framework was proposed to elicit underlying behavioural and cultural factors impeding food waste reduction and the inefficiency of food sharing. Using Paul Colaizzi’s approach, the collected interview data were reviewed, analysed, and seventeen themes were elicited for further discussion. The findings suggest that culture through an affluent way of life and the show-off lifestyle of hosts continue to contribute to more food wastage. The strictly business nature of restaurants operation leads to edible food fit for human consumption ending up in the garbage. The revised conceptual framework provides insight into the factors hindering food waste reduction and food sharing. With supporting regulations and policies, food leftovers can either be distributed to people in need or put to an alternative use.
    • Application of Hansen Solubility Parameters and Thermomechanical Techniques to the Prediction of Miscibility of Amorphous Solid Dispersion. Investigating the role of cohesive energy and free volume to predict phase separation kinetics in hot-melt extruded amorphous solid dispersion using dynamic mechanical analyser, shear rheometer and solubility parameters data

      Isreb, Mohammad; Gough, Timothy D.; Timmins, Peter; Mousa, Mohamad A.M.R. (University of BradfordSchool of Pharmacy. Faculty of Life Sciences, 2022)
      Hot-melt extruded solid dispersion technique is increasingly employed to improve the solubility of poorly water-soluble drugs. The technique relies on the enhanced solubility of the amorphous form of the drug compared to its crystalline counterpart. These systems however are thermodynamically unstable. This means that the drug crystallises with time. Therefore, efforts to measure the stability of these systems over the life span of the product are crucial. This study focused on investigating the use of Hansen Solubility Parameters to quantify polymer-drug interaction and to predict the stability of solid dispersions. This was achieved through a systematic review of hot-melt extruded solid dispersion literature. The study also investigated the use of a combined mechanical and rheological model to characterise the physicochemical and release behaviour of three solid dispersion immediately after preparation and after storage for one month at 40oC or three months at room temperature. Results revealed that the total solubility parameter |ΔбT| was able to predict the stability of the systems for more than 4 months using a cut-off point of 3 MPa-1 with a negative predictive value of 0.9. This was followed by ΔбD with a cut-off point of 1.5 MPa- 1. Moreover, Dynamic Mechanical Analyser and shear rheometry data were shown to be more sensitive than Differential Scanning Calorimetry, Powder X-Ray Diffraction, Scanning Electron Microscope and Fourier Transform Infrared in detecting crystallisation and the interaction between the drug and the polymer. The Dynamic Mechanical Analyser data were consistent with the dissolution behaviour of the samples when comparing the freshly prepared samples with those after storage. The results highlight the need for a unified characterisation approach and the necessity of verifying the homogeneity of mixing during the extrusion process.
    • Study of the Continuous Intention to use Artificial Intelligence Based Internet of Medical Things (IoMT) During Concurrent Diffusion. The Influence Diffusion of Innovation Factors Has as Determinants of Continuous Intention to Use Ai-Based IoMT

      Weerakkody, Vishanth J.P.; Sivarajah, Uthayasankar; Aldhaen, Fatema S.F.A. (University of BradfordFaculty of Management, Law and Social Sciences, 2022)
      This research was about the continuous intention of healthcare professionals to use internet of medical things (IoMT) embedded with artificial intelligence (AI). IoMT and AI are evolving innovations and diffusing at the same time. It was not known in what way the two complex technologies diffusing concurrently could influence continuous intention to use IoMT. In addition, behavioural aspects namely motivation and training to use IoMT have been argued to intervene in the relationship between an AI based IoMT and continuous intention to use IoMT. Diffusion of Innovation theory was applied to explain the relationship between diffusion factors that aid the diffusion of AI based IoMT and continuous intention to use IoMT. The five factors relative advantage, compatibility, complexity, observability and trialability were chosen as determinants of continuous intention to use IoMT using DoI theory. Self-determination theory and theory of planned behaviour were used to introduce the interventions in the relationship between diffusion factors and continuous intention to use IoMT. UTAUT was used to explain the influence of the moderators artificial intelligence awareness, novelty seeking behaviour and age of healthcare professionals. The central issue investigated was the determinants of continuous intention of healthcare professionals to use IoMT with behavioural attributes of motivation and training conceived as mediators of the relationship between diffusion factors and continuous intention to use IoMT in the presence of moderators. Quantitative research methodology was used to test the research model developed to understand the relationship between the five diffusion of innovation theory factors and continuous intention to use IoMT when AI based IoMT is still diffusing. The concurrent diffusion of two new technologies was investigated using a research model that was developed for studying the healthcare professionals and their intention. The research was conducted in Bahrain in the healthcare sector. A sample of 354 healthcare professionals participated in the research. Structural equation modelling was used to analyse the data and test the hypothesis. The research showed that healthcare professionals will continue to use concurrently diffusing technologies depending on the relative advantage, complexity and compatibility of the innovations that diffuse. In addition, the results show that healthcare professionals will be motivated by the compatibility of AI-based IoMT if they have to continuously use IoMT. Furthermore, training enables both the organization and the healthcare professionals to overcome dilemma in case they have to continue to use an innovation during its diffusion or when new innovation surface in the market. Finally, artificial intelligence awareness is able to moderate the relationship between relative advantage, complexity and training to use IoMT. Thus, this research contributes to the discipline of behavioural intention of healthcare professionals in determining the influence of an artificial intelligence based IoMT on continuous intention to use IoMT when artificial intelligence embedded in IoMT diffuses concurrently with IoMT. Where IoMT diffusion factors can be used as a determine of continuous intention to use IoMT, artificial intelligence could be understood as a moderator of the relationship between diffusion factors and training to use IoMT, thus demonstrating the combined diffusion of the two technologies diffusing concurrently.
    • Self-Congruity Theory: An Investigation of the Pro-Environmental Tourist Behaviours. An Application and Extension of Self-Congruity Theory of the Eco-Tourism Destinations in Pakistan and UK

      Trivedi, Rohit; Waseem, Donia; Amin, Obaidullah (University of BradfordSchool of Management. Faculty of Management, Law and Social Sciences, 2023)
      Pro-environmental behaviour has gained significant importance in tourism due to over-consumption and climate awareness. To address this issue, this study explores the role of self-congruity in aiding tourists to adopt pro-environmental behaviours. The study broadens the investigation around the self-congruity theory by incorporating three antecedents, i.e., need for uniqueness, materialistic values, and brand experience. Within the positivist paradigm, the study utilised the quantitative methodology; a survey was conducted in Hunza valley in Pakistan and the lake district in the UK. A total of 707 responses were collected from two eco-tourist destinations. Then, a set of hypotheses was tested using structural equational modelling. The results of the Pakistan study depicted that ideal self-congruity impacted Pakistani tourists pro-environmental behaviour. Results evidenced significant relationships of two dimensions of materialistic values, i.e., the centrality of acquisitions and pursuit of happiness, and two dimensions of need for uniqueness, i.e., creative choice counter conformity and unpopular choice counter, lastly, one dimension of brand experience, i.e., sensory brand experience, impacted the pro-environmental behaviours indirectly through ideal self-congruity. The results of the UK study depicted that actual self-congruity affected pro-environmental behaviours. The results portrayed that one dimension of materialistic values, i.e., the pursuit of happiness; one dimension of need for uniqueness, i.e., creative choice counter conformity and Lasty three dimension of brand experience, i.e., affective, behavioural and intellectual experience impacted the pro-environmental behaviour indirectly through the mediation of actual self-congruity. The study contributed theoretically by considering the multi-dimensional nature of self-congruity antecedents and their effects on pro-environment behaviour.
    • Investigation to Identify the Influence of the Surface Energetics of the Dry Powder Formulations of Budesonide and Theophylline on Their Aerodynamic Dose Emission Characteristics.

      Assi, Khaled H.; Vangala, Venu R.; Jamal, Abdullateef J.A.M.A. (University of BradfordSchool of Pharmacy. Faculty of Life Sciences, 2022)
      Surface energetics play a key role in the delivery of a dry powder inhaler formulation into the lungs, as there must be a sufficient balance of adhesive and cohesive forces to allow optimal lung delivery. In this study, measuring the surface energies of a set of single drug and carrier (budesonide or theophylline with either mannitol or lactose) with different levels of surfactant using Inverse Gas Chromatography, and comparing them to their lung deposition performance using a Next Generation Impactor established a relationship between the two. A 1:10 mixing ratio of budesonide with either carrier was found to have the highest FPF. Coating the carriers with 0.05% sodium lauryl sulphate resulted in a further increase in the FPF when using either budesonide or theophylline as the API, and the same results were seen when a sonocrystallised version of the API was substituted for the micronised form. The calculated IGC values then showed that the highest performing formulations had the lowest dispersive energy and total free surface energy. Furthermore, a trend was observed in the work of adhesion (Wa) and work of cohesion (Wc) for each set of formulations depending on which API was chosen, where for the less polar drug (budesonide) a higher Wa/Wc ratio was associated with the highest formulation performance, and for the more polar drug (theophylline) a smaller Wa/Wc ratio was associated with the highest formulation performance, enabling the estimation of lung performance for a set of single drug and carrier using their surface energy data.
    • An Evaluation of Technological, Organizational and Environmental Determinants of Emerging Technologies Adoption Driving SMEs’ Competitive Advantage

      Sivarajah, Uthayasankar; Rana, Nripendra P.; Vincent, Charles; Dobre, Marius (University of BradfordSchool of Management. Faculty of Management, Law, and Social Sciences, 2022)
      This research evaluates the technological, organizational, and environmental determinants of emerging technologies adoption represented by Artificial Intelligence (AI) and Internet of Things (IoT) driving SMEs’ competitive advantage within a resource-based view (RBV) theoretical approach supported by the technological-organizational-environmental (TOE)-framework setting. Current literature on SMEs competitive advantage as outcome of emerging technologies in the technological, organisational, and environmental contexts presents models focused on these contexts individual components. There are no models in the literature to represent the TOE framework as an integrated structure with gradual levels of complexity, allowing for incremental evaluation of the business context in support of decision making towards emerging technologies adoption supporting the firm competitive advantage. This research gap is addressed with the introduction of a new concept, the IT resource-based renewal, underpinned by the RBV, and supported by the TOE framework for providing a holistic understanding of the SMEs strategic renewal decision through information technology. This is achieved through a complex measurement model with four level constructs, leading into a parsimonious structural model that evaluates the relationships between IT resource-based renewal, and emerging technologies adoption driving SMEs competitive advantage. The model confirms the positive association between the IT resource-based renewal and emerging technologies adoption, and between the IT resource-based renewal and SME competitive advantage for the SMEs managers model, with the SME owners model outcomes are found not being supportive towards emerging technologies adoption driving SME competitive advantage. As methodology, PLS-SEM is used for its capabilities of assessing complex paths among model variables. Analysis is done on three models, one for the full sample, with two subsequent ones for owners and managers, respectively, as SME decision makers, with data collected using a web-based survey in Canada, the UK, and the US, that has provided 510 usable answers. This research has a theoretical contribution represented by the introduction of the IT resource-based renewal concept, that integrates the RBV perspective and the TOE framework for supporting organization’s decision on emerging technologies adoption driving SMEs competitive advantage. As practical implications, this thesis provides SMEs with a reference framework on adopting emerging technologies, offering SME managers and owners a comprehensive model of hierarchical factors contributing to SMEs competitive advantage acquired as outcome of AI and IoT adoption. This research makes an original contribution to the enterprise management, information systems adoption, and SME competitive advantage literature, with an empirical approach that verifies a model of emerging technologies adoption determinants driving SMEs competitive advantage.
    • Historic settlement on Unst, Shetland. An holistic study of abandoned settlements on Unst, Shetland utilising historical archaeology and prospection approaches

      Bond, Julie M.; Gaffney, Christopher F.; Heron, Carl P.; Legg, Robert M. (University of BradfordSchool of Archaeological and Forensic Sciences. Faculty of Life Sciences, 2018)
      A holistic study of abandoned house sites on the island of Unst was conducted to address the extent to which perceptions of historic settlement on Shetland are supportable. These perceptions cast long lived nucleated settlement as the normative traditional form of historic settlement, and dispersed settlements as short-lived exceptions to this norm. Historic settlement, in these perceptions are argued to be static, which is not borne out in archaeological evidence. Issues associated with historic Shetland settlement models were identified to parallel traditional views of Scottish highland rural settlement, which cast the highland society as ahistoric and unchanging. Historical, archaeological and geographic evidence for settlement on Unst were used to assess the geographical distribution of historic settlement on the island. Two detailed case studies integrated archaeological prospection techniques with the historical, archaeological and landscape contexts to form new narratives for the field remains around two abandoned house sites. Assessment of the historical settlement of Unst highlighted a much greater degree of variation between the different evidence strands for the perceptions to truly represent the island’s historical settlement. Similarly, findings from the case studies highlighted a much greater degree of alterations to the field systems and enclosures associated with the settlements than would be anticipated. Alternative narratives with several phases were hypothesised for field remains of each case study.
    • The therapeutic/anti-carcinogenic effect of cord blood stem cells-derived exosomes in malignant melanoma

      Najafzadeh, Mojgan; Anderson, Diana; Isreb, Mohammad; Baumgartner, Adolf; Wright, Andrew; Naeem, Parisa (University of BradfordFaculty of Life Sciences, 2022)
      Malignant melanoma is an invasive type of skin cancer with high mortality rates, if not detected promptly. The mortality trends are generally linked to multiple dysplastic nevi, positive family history, genetic susceptibility and phenotypic features including fair skin, freckles, numerous atypical nevi, light coloured hair and eyes, inability to tan and prolonged exposure to ultraviolet radiation B (UVB). To date, the major anti-cancer therapeutics for melanoma include surgery, chemotherapy, radiotherapy, and immunotherapy. Recently, extracellular vesicles, especially exosomes, have been highlighted for their therapeutic benefits in numerous chronic diseases such as cancer. Exosomes display multifunctional properties, including inhibition of cancer cell proliferation and initiation of apoptosis. Hence, this study aimed to evaluate the genotoxicity and cytotoxicity of cord blood stem cell-derived (CBSC) exosomes on 6 samples of peripheral blood lymphocytes taken from healthy individuals and melanoma patients and on 3 samples of melanoma (CHL-1) cells. The limited number of samples was due to the time limitations and restrictions that were in place due to the COVID-19 pandemic. In this in vitro study, the optimal concentration of CBSC-derived exosomes (0, 100, 200, 300, 400 μg/ml protein at 24, 48 and 72h treatments) was confirmed by the CCK-8 assay. CBSC exosomes (300 μg/ml) were used to treat lymphocytes and CHL-1 cells in the Comet assay and evaluated using the real-time polymerase chain reaction (qPCR) and Western blotting (WB). The data of the CCK-8 and Comet assays illustrated that exosomes exerted genotoxic effects on CHL-1 cells (CCK-8 assay, ****p < 0.0001), (Comet assay, *p <0.05, **p < 0.01). However, the data portraying a reduction in the viability of lymphocytes needs further investigation as the number of samples was limited, therefore, further clarification is required. Importantly, no significant adverse effect was observed in healthy lymphocytes when treated with the same exosomes (p = ns). When further challenged with UVA+B radiation, the exosomes did not induce any genoprotective effect on ROS-induced CHL-1 cells, compared to the positive control (p = ns). Our data insinuates that the damage might be caused by inducing apoptosis. The anti-tumourigenic potential of exosomes was observed by activating the p53-mediated apoptotic pathway in CHL-1 cells, up-regulating p53, p21 and caspase 3 and down-regulating BCL-2 at mRNA (**p < 0.01, ***p <0.001, ****p <0.0001) and protein levels (*p < 0.05, **p <0.01). The potency of CBSC exosomes in inhibiting cancer progression in CHL-1 cells whilst causing no harm to the healthy lymphocytes makes it an ideal potential candidate for anti-cancer therapy. More samples are required to evaluate the therapeutic effect of exosomes on lymphocytes from cancer patients to fully understand their mechanism of action.
    • Regional economic inequalities; migration and community response, with special reference to Yugoslavia

      Singleton, Frederick B. (1979)
      After a general introduction to the problems of regional imbalance, this paper proceeds to an analysis of the background and causes of regional economic inequalities in Yugoslavia. Demographic factors are outlined with reference to Yugoslav statistical sources, and the policies being adopted for those areas defined as being in need of special assistance are examined. The author concludes by indicating some lessons to be drawn from Yugoslavia's experience of migration and especially of its workers abroad.
    • Games and Learning: Consolidating and Expanding the Potential of Analogue and Digital Games

      Pinto Neves, P.; Sousa, C.; Fonseca, M.; Rye, Sara (2023-06-19)
      For a long time, Games Research suffered from what Jaakko Stenros and Annika Waern classified as the Digital Fallacy – the tendency to regard analog games as a subset of digital games rather than the other way around. Where boardgames were once associated with the past of games and learning and digital games with the future, there are now fresh insights and applications for boardgames in learning – alongside with their renaissance as games for entertainment. Even as boardgames found new relevance in learning, the already-recognized possibilities in digital games for learning have continued to expand, with more flexible and ubiquitous tools and platforms allowing for a greater variety of avenues of learning research and practice to be explored. Augmented and mixed reality as well as virtual reality are frontiers in learning that beg for further exploration.
    • Fabrication Characterisation and Optimisation of Electrospun Scaffolds for Ligament Tissue Reconstruction. The Development of an Anterior Cruciate Ligament (ACL) Analogue using Electrospun PCL, PVA Hydrogel and Polyester Sutures

      Sefat, Farshid; Twigg, Peter C.; Agbabiaka, Oluwadamilola A. (University of BradfordSchool of Biomedical and Electronics Engineering. Faculty of Engineering and Informatics, 2022)
      Year 2019, football, rugby, netball and skiing had most occurring ACL injuries, listed by United Kingdom National Ligament Report (NLR). The standard procedure treatment of complete laceration of the ACL, is performed by tissue autograft implantation designed from a patellar tendon, for replacement of damaged tissue using orthopaedic surgery. The aim of this thesis is to design and fabricate an ACL graft, attempting to mimic the natural ACL, for the purpose of tissue reconstruction. The desired graft analogues exhibited properties imitating native connective tissue, reducing pain through drug delivery with great biocompatibility and enhance suture mechanical strength. Various biomaterials were implemented into this study, utilising strategies; polymer solution fabrication, electrospinning, hydrogel synthesis, mechanical braiding and graft assembly to fabricate an ACL graft. The polymeric material poly (E- caprolactone) (PCL) was researched, utilising its ability to fabricate scaffolds. Results showed, three analogue ACL grafts (Braided PCL-BP, Braided PCL + Hydrogel-BPH & Braided PCL + Sutures-BPS) created utilising the properties of braiding, hydrogels and sutures, ultimately improving the versatility of electrospinning for tissue engineering and reconstruction. Graft analogues were tested and compared against patellar tendons producing similar tensile properties. Poly vinyl alcohol (PVA) hydrogels successfully held ibuprofen, revealing drug delivery characteristics, polyester threads improved mechanical properties of electrospun grafts and dry degradation showed that PCL did not lose significant mass over two months. Conclusion, tensile strength of patella tendon was 395x, 790x & 56x of analogue grafts (BP, BPH & BPS) respectively, having potential for improvement of tensile parameters for ligament reconstruction.
    • Sparse Representation and its Application to Multivariate Time Series Classification

      Lei, Ci; Neagu, Daniel; Sani, Habiba M. (University of BradfordDepartment of Computer Science. Faculty of Engineering and Informatics, 2022)
      In signal processing field, there are various measures that can be employed to analyse and represent the signal in order to obtain meaningful outcome. Sparse representation (SR) has continued to receive great attention as one of the well-known tools in statistical theory which among others, is used to extract specific latent temporal features that can reveal salient primitive and sparsely represented features of complex data signals, including temporal data analysis. Under reasonable conditions, many signals are assumed to be sparse within a domain, such as spatial, time, or timefrequency domain, and this sparse characteristics of such signals can be obtained through the SR. The ECG signal, for instance, is typically a temporal sparse signal, comprises of various periodic activities such as time delay and frequency amplitudes, plus additive noise and possible interference. Particularly challenging in signal processing, especially time series signals is how to reconstruct and extract the various features that characterized the signal. Many problems (e.g., signal components analysis, feature extraction/selection in signals, signal reconstruction, and classification) can be formulated as linear models and solved using the SR technique The reconstruction of signals through SR can offer a rich representation of the sparsified temporal structure of the original signal. Due to its numerous advantages, such as noise tolerance and widespread use in various signal processing tasks, this has motivated many researchers to adopt the use of this technique for various signal representation analysis for a better and richer representation of the original input signal. In line with this, therefore, the goal of this study is to propose a SR-based mathematical framework and a coherence function for reconstruction and feature extraction from signals for subsequent analysis. The time embedding principle was first applied to restructure the signal into tine delay vectors and then the proposed approach, referred to as temporal subsequence SR approach was used to reconstruct the noisy signals and provides a sparsified time dependent input signal representation, and then the coherence function is further used to compute and extract the correlational coefficient quantities between the temporal subsequence signals to form the final feature vectors representing the discriminative features for each of the signal. These final feature vectors representing the signal are further used as inputs to machine learning classifiers. Experiments are carried out to illustrate the usefulness of the proposed methods and to assess their impact on the classification performance of the SVM and MLP classifiers using the popular and widely used ECG time series benchmark dataset. This research study supports the general hypothesis that, signal reconstruction methods (datadriven approach) can be valuable in learning compact features from the original signals for classifications.
    • Analysing product attributes of refurbished laptops based on customer reviews and ratings: machine learning approach to circular consumption

      Ghosh, A.; Pathak, D.; Bhola, P.; Bhattacharjee, D.; Sivarajah, Uthayasankar (2023)
      Reviews and ratings of consumers towards a product impact consumer decision-making and their perceptions. Such information is key in measuring consumer satisfaction and net promoter scores. However, when the reviewed products are refurbished, consumer reviews become more important because information influences consumer behaviour and attitude toward looped products. This research explores the decision-influencing attributes of consumers while purchasing refurbished goods using quantitative and qualitative methods. Online after-sales 1986 laptop customers’ review and rating data in the public domain were analysed to reveal the decision-influencing attributes and their impact on potential consumers. The study envisions assisting the operations of sellers in the refurbished market by strengthening their businesses' value proposition and stimulating reverse logistics entrepreneurs to use the opportunity. Review data containing lifecycle valuation of old laptops induced feature extraction by machine learning applications. It is beneficial to sellers in the refurbished product segment. It provides information to strengthen their value proposition and is informative to entrepreneurs wanting to enter the segment. Based on the text analysis of consumer reviews, the study's results show that price, brand, design, performance, services, and utility influence consumers. The frequency analysis technique was used to extract attributes, followed by content analysis and feature selection using SHapley Additive exPlanations (SHAP) for exploring correlations between features and star ratings. Lastly, multinomial logistic regression was used to validate the generated model. The results show that brand, design, price, and utility are the most prominent attributes influencing consumers' decision-making with positive sentiments. In contrast, performance and services often generate neutral and negative sentiments.
    • Towards the development of an integrated case-finding tool to facilitate the review of anticholinergic prescribing for frail older people

      Petty, Duncan R.; Faisal, Muhammad; Johnson, O.A.; Gardner, Peter H.; Mehdizadeh, David (University of BradfordSchool of Pharmacy and Medical Sciences. Faculty of Life Sciences, 2022)
      Background: The cumulative effect of taking anticholinergic medicines (anticholinergic burden) is associated with adverse outcomes for older people. Prevalence of anticholinergic prescribing is increasing, and there is a need for tools to proactively identify at-risk patients for medication reviews. Aim: To explore the need for, and feasibility of, an integrated case-finding tool that predicts risks using electronic health records (EHRs), facilitating the review of anticholinergic medicines for frail older people. Methods: Mixed methods, adopting a pragmatic approach. A systematic review, prediction modelling of cohort study data, and qualitative interviews were undertaken. Results: The systematic review found anticholinergic exposure was associated with adverse outcomes for the frail; poorer physical function, falls, and mortality, indicating a need for a risk reducing intervention. In the prediction modelling study, predicting risks using composite measures of anticholinergic burden and frailty indicated limited feasibility. Neither enhanced the performance of best subset models using cohort study data. Their predictive utility needs to be investigated using EHR data, to determine their feasibility within primary care. The qualitative study found healthcare professionals needed a proactive tool, supporting risk prediction as a feasible approach. Factors influencing future implementation were; upskilling requirements, deprescribing confidence, patient reluctance, motivation, holistic care, interoperability, trust in risk prediction, remuneration, among other barriers and facilitators. Conclusions: Through identifying a need, and potential feasibility, foundations towards the future developments of a case-finding tool have been provided, informing an early tool prototype (AC-FRAIL). Recommendations for further work suggest a roadmap ahead, to maximise the potential for integrated solutions to proactively reduce anticholinergic risks.
    • The effect of corporate ethical responsibility on social and environmental performance: An empirical study

      Bag, S.; Srivastava, G.; Gupta, S.; Sivarajah, Uthayasankar; Wilmot, N.V. (2024-02)
      In the field of business-to-business marketing, corporate ethical identity and corporate brand identity are crucial subjects for discussion. Business organizations function under social norms, and to establish an ethical identity, they must show corporate ethical responsibility, embrace ethical standards, and maintain open communication with suppliers. While an organization's reputation is impacted by the absence of an ethical identity, its financial success is unaffected. Extant literature has not thrown a spotlight on social and environmental performance which indicates that less focus has been given by academics than by practitioners. To fill the lacuna in the existing literature, this study examines the relationships between corporate ethical identity, corporate brand identity, social and environmental performance. The study uses a deductive research approach and develops hypotheses which are further tested using variance based structural equation modeling. The study offers a distinctive contribution to ethics theory and stakeholder theory by showing that developing an ethical identity requires more than just adhering to moral guidelines and upholding open communication. Companies must show that they are ethically responsible towards society. The study provides evidence of the influence corporate brand identity has on environmental and social performance. The findings can be useful in developing business-to-business marketing strategies.
    • In situ monitoring of competitive coformer exchange reaction by 1H MAS Solid-state NMR

      Hareendran, C.; Alsirawan, B.; Paradkar, Anant R; Ajithku, T.G.am (American Chemical Society, 2024-03)
      In a competitive coformer exchange reaction, a recent topic of interest in pharmaceutical research, the coformer in a pharmaceutical cocrystal is exchanged with another coformer which is expected to form a cocrystal that is more stable. There will be a competition between coformers to form the most stable product through formation of hydrogen bonds. Thus, to monitor each and every step of such reactions, employing a very sensitive technique is crucial. 1H nuclear magnetic resonance (NMR) is a very powerful technique that is very sensitive to the hydrogen bond interactions. In this study, an in situ monitoring of a coformer exchange reaction is carried out by 1H magic angle spinning (MAS) solid-state NMR (SSNMR) at a spinning frequency of 60 KHz. The changes in caffeine maleic acid cocrystals on addition of glutaric acid, and caffeine glutaric cocrystal on addition of maleic acid were monitored. In all the reactions, it has been observed that caffeine glutaric acid Form I is formed. When glutaric acid was added to 2:1 caffeine maleic acid, the formation of metastable 1:1 caffeine glutaric acid Form I was observed, at the start of the experiment, indicating that the centrifugal pressure is enough for the formation. The difference in the end product of the reactions with similar reaction pathway of 1:1 and 2:1 reactant stoichiometry indicate that a complete replacement of maleic acid has only occurred only in the 1:1 stoichiometry of the reactants. The polymorphic transition of caffeine glutaric acid Form II to Form I at higher temperature was crucial reason which triggers the exchange of glutaric acid with maleic acid in the reaction of caffeine glutaric acid and maleic acid. Based on these results, new reaction pathways in competitive coformer exchange reactions could be distinguished, and the remarkable role of stoichiometry, polymorphism, temperature and centrifugal pressure could be established.
    • Sentiment Matters: The effect of news-media on spillovers among cryptocurrency returns

      Akyildirim, Erdinc; Aysan, A.F.; Cepni, O.; Serbest, O. (2024)
      This paper explores the relationship between news media sentiment and spillover effects in the cryptocurrency market. By employing a time-varying parameter vector autoregressive model, we initially develop measures of spillover specific to individual cryptocurrencies. Subsequently, we employ unique data on cryptocurrency-specific sentiment to assess its impact on these spillover measures using panel fixed effects regression analysis. Our findings indicate that news media sentiment plays a significant role in explaining the spillover dynamics within the cryptocurrency market. Unlike traditional assets, it appears that only positive sentiment affects the spillovers among cryptocurrencies, suggesting an asymmetric effect. Taking into account various characteristics of cryptocurrencies, we find that sentiment’s impact on spillover is more pronounced in community-based coins than in those driven by firms. An examination of news content suggests that sentiment pertaining to emotional and risk aspects of cryptocurrencies predominantly influences these spillovers. Additionally, a comparative analysis of sentiment derived from social media and traditional news sources reveals a stronger influence of the former on spillover effects. Through extensive robustness checks, our research consistently affirms the pivotal role of sentiment in driving spillovers among cryptocurrency returns, underlining the importance of sentiment analysis in understanding the dynamics of the cryptocurrency market.
    • Proteomic Investigation of Endocrine Therapy Resistance in Breast Cancer Investigating the Molecular Mechanisms for SERM Resistant Cell Lines Using SILAC-Based Proteomic Approach

      Sutton, Chris W.; Shnyder, Steven; Al-Kabariti, Aya Y. (University of BradfordSchool of Pharmacy. Faculty of Life Sciences, 2022)
      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.
    • Hepatitis B virus infection on Kwajalein Atoll, Marshall Islands: a seroprevalence, knowledge and attitudes study

      Lawanivalu, M.; Ratu, A.; Jeadrik, G.; Mohammadnezhad, Masoud; Strobel, A. (2024-02-21)
      Objective: A study was conducted to determine the seroprevalence of chronic hepatitis B virus (HBV) infection among children and their mothers on Kwajalein Atoll in the Marshall Islands two decades after routine vaccination was introduced in the 1990s. Mothers’ knowledge and attitudes towards HBV disease and vaccination were also assessed. Methods: Results of a national seroprevalence survey conducted in 2016–2017 and antenatal records were used to determine the prevalence of HBV seropositivity in children aged 6–8 years and their biological mothers. The associations between demographic, social and vaccination-related factors and seropositivity were explored using Fisher’s exact tests. Results: HBV seroprevalence was 0.3% in children and 6.8% in their mothers (during pregnancy). Coverage of timely HBV vaccination was 90.3% for the birth dose and was significantly associated with factors related to place of residence (P < 0.001), place of birth (P < 0.001) and number of antenatal visits (P < 0.001). Maternal attitudes towards infant vaccination and antenatal screening were largely positive (95.8% and 96.7%, respectively) despite low vaccination rates (20.9%) among mothers. Knowledge levels were low for disease complications, treatment and transmission. Discussion: Prevalence of HBV in children and mothers residing on Kwajalein Atoll in 2016–2017 was lower than the national average for the Marshall Islands. Timely birth dose administration appears to have been effective in preventing mother-to-child transmission of HBV in this setting and should be promoted in remote settings where antiviral therapy is not available. Provision of out-of-cold-chain HBV vaccines should be considered to improve access in remote settings.