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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.University of Bradford under the SURE Grant scheme
Experiences of patients with heart failure with medicines at transition intervention: Findings from the process evaluation of the Improving the Safety and Continuity of Medicines management at Transitions of care (ISCOMAT) programme
No full textYesBackground: Medicines are often suboptimally managed for heart failure patients across the transition from hospital to home, potentially leading to poor patient outcomes. The Improving the Safety and Continuity Of Medicines management at Transitions of care programme included: understanding the problems faced by patients and healthcare professionals; developing and co-designing the Medicines at Transitions of care Intervention (MaTI); a cluster randomized controlled trial testing the effectiveness of a complex behavioural MaTI aimed at improving medicines management at the interface between hospitals discharge and community care for patients with heart failure; and a process evaluation. The MaTI included a patient-held My Medicines Toolkit; enhanced communication between the hospital and the patient's community pharmacist and increased engagement of the community pharmacist postdischarge. This paper reports on the patients' experiences of the MaTI and its implementation from the process evaluation.
Design: Twenty one-to-one semi-structured patient interviews from six intervention sites were conducted between November 2018 and January 2020. Data were analysed using the Framework method, involving patients as co-analysts. Interview data were triangulated with routine trial data, the Consolidated Framework for Implementation Research and a logic model.
Results: Within the hospital setting patients engaged with the toolkit according to whether staff raised awareness of the My Medicines Toolkit's importance and the time and place of its introduction. Patients' engagement with community pharmacy depended on their awareness of the community pharmacist's role, support sources and perceptions of involvement in medicines management. The toolkit's impact on patients' medicines management at home included reassurance during gaps in care, increased knowledge of medicines, enhanced ability to monitor health and seek support and supporting sharing medicines management between formal and informal care networks.
Conclusion: Many patients perceived that the MaTI offered them support in their medicines management when transitioning from hospital into the community. Importantly, it can be incorporated into and built upon patients' lived experiences of heart failure. Key to its successful implementation is the quality of engagement of healthcare professionals in introducing the intervention.
Patient or Public Contribution: Patients were involved in the study design, as qualitative data co-analysts and as co-authors.Programme Grants for Applied Research. Grant Number: RP-PG-0514-2000
Environmental Hydraulics, Turbulence and Sediment Transport
No full textYesIn the research on environmental hydraulics, its turbulence and sediment transport, constant challenges have been faced. The complexity of hydraulic impacts towards sediment morphology and turbulent flow properties makes research in this area a difficult task. However, due to pressure from climate change and the mounting issue of pollution, environmental flow studies are more crucial than ever. Bedforming within rivers is a complex process that can be influenced by the hydraulics, vegetated field, and various suspended and bedload transports. Changes in flow conditions due to rain and flood can further complicate a hydraulic system. To date, the turbulence, morphologic, and bedforming characteristics of natural environmental flows are still not well understood. This book aims to bring together a collection of state-of-the-art research and technologies to form a useful guide for the related research and engineering communities. It is useful for authorities and researchers interested in environmental and civil engineering studies, as well as for river and water engineers to understand the current state-of-the-art practices in environmental flow modelling, measurement and management. It is also a good resource for research, post-, or undergraduate students who wish to know about the most up-to-date knowledge in this field
Formulation and Characterization of Phytosomes as Drug Delivery System of Formononetin: An effective Anti-Osteoporotic Agent
No full textNoFormononetin (FNT), a methoxy isoflavone, is a potential phytoconstituent utilized for refurbishing fractures in bone tissue. Conceding to its involvement in first-pass metabolism followed by glucuronidation, its absorption efficacy is limited. Hence, it belongs to the BCS class II classification.
We designed the present work to enhance FNT oral bioavailability by using Phospholipids (PL) as a promising carrier. Formononetin Phospholipid Complex (FNT-PC) was prepared by the solvent evaporation method and characterized.
FNT-PC was prepared by solvent evaporation method and characterization (FNT-PC) was performed using aqueous/n-octanol solubility and partition coefficient, FTIR, NMR, SEM, and in vivo pharmacokinetic study in female SD rats at 50mg/kg.
Physicochemical properties like aqueous/n-octanol solubility and partition coefficient were enhanced in FNT-PC. The FTIR spectrum confirmed there was no involvement of functional groups in the preparation of FNT-PC. Whereas, the NMR study resulted in the attachment of carbon (C-8) position of FNT by replacing the quaternary amine of PL to form FNT-PC. When scrutinized for its surface morphology, the FNT-PC exhibited the amorphous geometry that remarkably enhanced the dissolution of FNT (p<0.05) from its pure form. This dissolution effect was also affirmed by the per-oral administration of FNT-PC in female Sprague Dawley (SD) rats at 50 mg/kg dose. The pharmacokinetic profile showed the free FNT levels were markedly increased, correspondingly decreasing the conjugated FNT levels in rat plasma.
To summarize, FNT-PC could substantially reduce the first-pass metabolism with enhanced free concentration, improving oral bioavailability for therapeutic use
New aldo-keto reductase 1C3 (AKR1C3) inhibitors based on the hydroxytriazole scaffold
No full textYesThe aldo-keto reductase 1C3 (AKR1C3) enzyme is considered an attractive target in Castration Resistant Prostate Cancer (CRPC) because of its role in the biosynthesis of androgens. Flufenamic acid, a non-selective AKR1C3 inhibitor, has previously been subjected to bioisosteric modulation to give rise to a series of compounds with the hydroxytriazole core. In this work, the hit compound of the previous series has been modulated further, and new, more potent, and selective derivatives have been obtained. The poor solubility of the most active compound (cpd 5) has been improved by substituting the triazole core with an isoxazole heteronucleous, with similar enzymatic activity being retained. Potent AKR1C3 inhibition is translated into antiproliferative effects against the 22RV1 CRPC cellular model, and the in-silico design, synthesis and biological activity of new compounds is described herein. Compounds have also been assayed in combination with two approved antitumor drugs, abiraterone and enzalutamide.This research was financially supported by the University of Turin (Ricerca Locale grants BOSD_RILO_20_01, LOLM_RILO_21_01, PIPA_RILO_20_01 and PIPA_RILO_21_01), Fondazione Cassa di Risparmio di Torino (Grant BOSD_CRT_17_2) and TUBITAK (The Scientific and Technological Research Council of Turkey-2219 program)
The MK2 cascade mediates transient alteration in mGluR-LTD and spatial learning in a murine model of Alzheimer's disease
Get PDFYesA key aim of Alzheimer disease research is to develop efficient therapies to prevent and/or delay the irreversible progression of cognitive impairments. Early deficits in long-term potentiation (LTP) are associated with the accumulation of amyloid beta in rodent models of the disease; however, less is known about how mGluR-mediated long-term depression (mGluR-LTD) is affected. In this study, we have found that mGluR-LTD is enhanced in the APPswe /PS1dE9 mouse at 7 but returns to wild-type levels at 13 months of age. This transient over-activation of mGluR signalling is coupled with impaired LTP and shifts the dynamic range of synapses towards depression. These alterations in synaptic plasticity are associated with an inability to utilize cues in a spatial learning task. The transient dysregulation of plasticity can be prevented by genetic deletion of the MAP kinase-activated protein kinase 2 (MK2), a substrate of p38 MAPK, demonstrating that manipulating the mGluR-p38 MAPK-MK2 cascade at 7 months can prevent the shift in synapse dynamic range. Our work reveals the MK2 cascade as a potential pharmacological target to correct the over-activation of mGluR signalling.Wellcome Trust, Grant/Award Number: 200646/Z/16/
Experimental Test of Two Span Continuous Concrete Beams Reinforced with Hybrid GFRP-Steel Bars
Get PDFYesThe current paper aimed at investigating the flexural performance of five large-scale continuous concrete beams reinforced by both steel bars and glass fibre reinforced polymer (GFRP). All the studied specimens had the same geometrical dimensions, with 200mm width, 300mm depth, and two identical spans of 2600mm. The quantity of longitudinal steel reinforcement, GFRP reinforcement, and hybrid reinforcement ratio at the top and bottom layers of beams were the key parameters explored in this study. The experimental findings indicated that using the hybrid reinforcement of steel and GFRP in multi-span continuous concrete beams exhibited a ductile behaviour. However, the hybrid ratio of steel bars/GFRP is critical for restricting the extent of moment redistribution ratios. Moreover, using the same hybrid reinforcement ratios at sagging and hogging regions led to a limited moment redistribution. On the other hand, the hybrid beams strengthened by various hybrid ratios in the critical sections of the tested beams demonstrated a remarkable moment redistribution up to 43%.
The test results were compared with the available theoretical model and equations for predicting the beams' moment capacity. It was found that the ACI.440.2R-08 reasonably predicted the flexural capacity of tested beams whereas the Yinghao and Yong equation underestimated the flexural capacity in the hogging sections. It was also shown that using the collapse mechanism with plastic hinges at sagging and hogging sections yielded good predictions for the loading capacity of hybrid reinforced concrete continuous beams
Psychology for the Common Good: The Interdependence of Citizenship, Justice, and Well-being across the Globe
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Living with dementia during the COVID-19 pandemic: insights into identity from the IDEAL cohort
Get PDFYesThe continuing COVID-19 pandemic and social restrictions have impacted on the cognitive decline and mental health of people with dementia. Social isolation and loss of activities due to social restrictions may also have implications as to sense of identity for people with dementia. As part of the INCLUDE (Identifying and Mitigating the Individual and Dyadic Impact of COVID-19 and Life Under Physical Distancing on People with Dementia and Carers) component of the IDEAL (Improving the Experience of Dementia and Enhancing Active Life) cohort study, the overall aim of this subtle realist qualitative study was to explore the perspectives of people with dementia on living through the COVID-19 pandemic within the context of the ‘post-vaccine’ period and the national lockdowns in England and Wales; and to determine perceived challenges to and facilitators of ‘living well’ during the COVID-19 pandemic and beyond as restrictions were eased. In addition, the study findings are considered in relation to understandings of identity in dementia which the broader accounts of living through the pandemic have highlighted. Seven people with mild-to-moderate dementia were interviewed and themes were derived using framework analysis. Themes suggest interviewees' stoic acceptance of the pandemic and social restrictions but also fear of decline related to the temporality of their condition as well as loss of self-confidence to re-engage with the world. Interviewees managed threats to social identity by striving to maintain social and emotional connections, where the importance of a shared, social identity, particularly for people with young-onset dementia, was also apparent. Unlike in previous studies during the pandemic, the relevance of occupation for identity was observed, where maintaining previous or new activities or occupations was important to facilitate identity as well as to keep a sense of purpose. Therefore, as well as supporting people with dementia as the pandemic eases, future research into occupation and identity in dementia is of potential value.‘Identifying and Mitigating the Individual and Dyadic Impact of COVID-19 and Life Under Physical Distancing on People with Dementia and Carers (INCLUDE)’ was funded by the Economic and Social Research Council (ESRC; grant number ES/V004964/1)