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The therapeutic/anti-carcinogenic effect of cord blood stem cells-derived exosomes in malignant melanoma
Get PDFMalignant 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
Strategic Decision-making Process in the Qatari Public Sector. Relationship between the Decision-Making Process, Implementation, and Outcome
Get PDFAlthough several multi-dimensional models of strategic decision-making processes (SDMPs) have been examined in the literature, these studies have paid insufficient attention to the public sector context and Gulf Cooperation Council (GCC) region. SDMP in the public sector and the State of Qatar can vary to SDMP in the private sector due to institutional and socio-cultural differences respectively. Therefore, more research is urgently needed to better understand SDPM within this context.
To contribute to filling this void, this study develops and tests a multi-dimensional SDMP model including SDMP dimensions, implementation, and outcome. The study model examines () the impact of four SDMP dimensions—procedural rationality, intuition, constructive politics, and participation—on the implementation success of the strategic decision; () the impact of the successful implementation of SD over the SD quality; () the mediation role of the implementation success of SD; () the moderation effect of stakeholder uncertainty.
The model was analysed using Partial Least Square Structural Equation Modelling (PLS-SEM) and tested using data from multiple informants on 170 strategic decisions in 38 Qatari public organisations. The study finds that procedural rationality, constructive politics, participations, and the implementation Success of SD plays a significant and positive role on SDMP and its overall outcome. Finally, the study provides substantial and original contributions to the knowledge of SDMP in the public sector; implications for decision-makers and directions for future research
Is firm-level political risk priced in the equity option market?
Get PDFYesWe find a negative relation between firm-level political risk and future delta-hedged equity option returns. A quasi-natural experiment based on Brexit corroborates this finding since after the
referendum there is a decrease in the option returns of the positive-Brexit exposure firms. The
predictability is driven by the jump risk component of political uncertainty, is more pronounced
in periods of high intermediary constraints and is stronger among high-demand pressure options
but weaker among politically active firms. Finally, consistent with a risk-based explanation, investors of options on politically risky firms get compensated with high returns when major unexpected political shocks take place
Factors affecting childhood immunization: Thematic analysis of parents and healthcare workers' perceptions
Get PDFYesImmunization against common childhood diseases is an important strategy as it is critical for reducing the global child morbidity and mortality. This review explores the perceptions of parents and HCWs toward childhood immunization. The PRISMA guideline was used to search and include the studies. Relevant electronic databases were systemically searched for the years ranging from 2000 to 2021 to identify studies reported in English. Themes were then identified using thematic analysis. A total of 44 studies met the review criteria and were summarized and categorized into 4 themes: barriers to immunization, parental knowledge, attitude and behavior (KAB), health system factors and HCWs’ KAB. This review found that immunization decision-making is a complex process. Parental KAB leads to immunization decisions. HCWs were also noted to be the trusted sources of immunization information. Further research can be conducted on how to improve parents’ perceptions of immunization and immunization practices
The Impact of Legacy Systems on Digital Transformation in European Public Administration: Lesson Learned from a Multi Case Analysis
Get PDFYesLegacy systems have continued to pose a major challenge to digital transformation efforts in public administration. A comprehensive review of literature suggests seven levels of complexity in transforming legacy systems, including, being a stand-alone system, being part of a larger system, and data incompatibility, each depicting unique criteria and challenges. Nonetheless, very little is known as to what degree these complexities implicate the implementation of digital transformation efforts in public administration (PA). To address this gap, this research conducted an analysis on four cases of digital transformation in three European PA settings (i.e., Denmark, the Netherlands, and the UK). The findings revealed complexities that pose the key challenges to systems interoperability and integrability, which are crucial in any digital transformation project. In addition, a comprehensive understanding of the systems to be transformed, the policies which they are serving, and the broader PA setting in which they are implemented were deemed central to succeeding in digital transformation efforts
Self-sensing cementitious composites with hierarchical carbon fiber-carbon nanotube composite fillers for crack development monitoring of a maglev girder
Get PDFYesIn view of high-performance, multifunctional and low-carbon development of infrastructures, there is a growing demand for smart engineering materials, making infrastructures intelligent. This paper reports a new-generation self-sensing cementitious composite (SSCC) incorporated with a hierarchically structured carbon fiber-carbon nanotube composite filler (CF-CNT), which is in-situ synthesized by directly growing CNT on CF. Various important factors including catalyst, temperature, and gas composition are considered to investigate their kinetic and thermodynamic influence on CF-CNT synthesis. The reciprocal architecture of CF-CNT not only alleviates the CNT aggregation, but also significantly improves the interfacial bonding between CF-CNTs and matrix. Due to the synergic and spatially morphological effects of CF-CNT, i.e., the formation of widely distributed multiscale reinforcement networks, SSCCs with CF-CNTs exhibit high mechanical properties and electrical conductivity as well as excellent self-sensing performances, particularly enhanced sensing repeatability. Moreover, the SSCCs with CF-CNTs are integrated into a full-scale maglev girder to devise a smart system for crack development monitoring. The system demonstrates high sensitivity and fidelity to capture the initiation of cracks/damage, as well as progressive and sudden damage events until complete failure of the maglev girder, indicating its considerable potential for structural health monitoring of infrastructures.The work described in this paper is supported by grants from the National Science Foundation of China (51978127 and 51578110) and grants from the China Postdoctoral Science Foundation (2022M710973 and 2022M720648)
The role of children's hospices in perinatal palliative care and advance care planning: the results of a national British survey
Get PDFYesperinatal palliative care services are increasingly available globally, offering a range of clinical and psychological support services to families during pregnancy, in the neonatal period and following the death of a baby with a life-limiting or life-threatening condition. Little is understood about the role of children’s hospice care and how it contributes to effective perinatal palliative care.
Design: The study aims to answer the question ‘what is the role of children’s hospices in the provision of perinatal palliative care and advance care planning in the United Kingdom?’
Methods: An electronic survey was sent to all 54 children’s hospices in the United Kingdom between May and June 2022.
Results: 30 hospices responded, representing 54% of the sector. All regions of all four counties are represented. Numbers of referrals to hospices for perinatal palliative care have increased significantly over the last five years. Hospices provide a range of services for families and babies, usually from the point of diagnosis or recognition of a life-limiting or life-threatening condition, underpinned with counselling and emotional support. Hospices worked with a range of professionals and services, most commonly fetal medicine and neonatal services. Advance care plans were an important element of effective perinatal palliative care, strengthening parent-professional and interprofessional relationships.
Conclusion: Children’s hospice services play an important and growing role in the perinatal care of babies and families following the diagnosis or recognition of a life limiting or life-threatening condition. The family centred approach to care, from a broad, biopsychosocial perspective means that hospices make a unique and meaningful contribution to both the clinical and psychological needs of families.University of Bradford. Grant Number: DA5151. SURE Research Projec
Challenges with Providing Reliability Assurance for Self-Adaptive Cyber-Physical Systems
No full textNoSelf-adaptive systems are evolving systems that can
adjust their behaviour to accommodate dynamic requirements
or to better serve the goal. These systems can vary in their
architecture, operation, or adaptive strategies based on the
application. Moreover, the evaluation can happen in different
ways depending on system architecture and its requirements.
Self-adaptive systems can be prone to situations like adaptation
faults, inconsistencies in context or low performance on tasks due
to their dynamism and complexity. That is why it is important to
have reliability assurance of the system to monitor such situations
which can compromise the system functionality. In this paper, we
provide a brief background on different types of self-adaptive
systems and various ways a system can evolve. We discuss the
different mechanisms that have been applied in the last two
decades for reliability evaluation of such systems and identify
challenges and limitations as research opportunities related to
the self-adaptive system’s reliability evaluation.This research was undertaken as a part of the “Model-based Reliability Evaluation for Autonomous Systems with Evolving Architectures” project funded by the University of Bradford under the SURE Grant scheme
Wake flow field of a wall-mounted pipe with spoiler on a rough channel bed
Get PDFYesThis research work focuses on the wake flow region of a cylinder with a spoiler on a rough bed under steady flow conditions. The acoustic Doppler velocimetry was used for the measurement of three-dimensional velocity data for two Reynolds numbers in a fully developed turbulent flow around the cylinder with a spoiler. The mean flow velocities, second-order turbulence structures, and conditional statistics were investigated in the wake region of the spoilered cylinder. The flow was separated from the spoiler with the formation of two shear layers between free surface flow and recirculating flow. It is observed that the flow is reattaching to the bed at 11D irrespective of the Reynolds number. Downstream of the cylinder, the mean velocity distributions are asymmetric due to the wall–wake effect, and the point of inflection is observed for each velocity profile at z = 0.40ẟ. The turbulence intensities, Reynolds stresses, and TKE are highly enhanced in the wake region of the cylinder as compared to their respective upstream values for both runs. The turbulence intensities, Reynolds normal stresses, Reynolds shear stresses, and turbulent kinetic energy are attaining peaks at z = 0.4 ẟ for all the streamwise locations, and the peaks are found to be highest at x = 10D. The quadrant analysis results indicate that the sweeps are dominating bursting events in the inner and intermediate layers, while ejections are dominating in the outer layer of the wake region. As the hole size, H increases ejections stress fraction rises as compared to that of the sweeps in the wake region for z = 0.2–0.7 h
