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Implementing a digital physical activity intervention for older adults: qualitative study
No full textBackground: physical activity (PA) in older adults can prevent, treat, or offset symptoms and deterioration from various health conditions and help maintain independence. However, most older adults are insufficiently active. Digital interventions have the potential for high reach at low cost.Objective: this paper reports on the implementation of “Active Lives,” a digital intervention developed specifically for older adults.Methods: this study had a qualitative design. The implementation team approached a range of National Health Service, public health, community, and third-sector organizations in the United Kingdom to offer Active Lives to as large and diverse groups of older adults as possible. Alongside real-world implementation activities, research was conducted to explore what supports and inhibits the implementation of a digital intervention for PA in older adults. Data collection involved interviews with implementation partners (n=15) and the implementation team (n=3) plus extensive field notes from stakeholder communications. Inductive thematic analysis was used to analyze the data.Results: five broad themes were developed, capturing implementation barriers and facilitators. These were (1) complex and opaque networks and influencers, (2) forming an understanding of Active Lives and its fit, (3) a landscape of competition and conflicting interests, (4) navigating unclear approval processes, and (5) shifting strategies: small and effortful to high reach and passive. Identifying key decision makers proved arduous, consuming significant time and resources, and proposals from enthusiastic implementation partners often proved impractical or overly burdensome. Health care professionals demonstrated a comprehensive understanding of the potential benefits of digital interventions in alleviating operational burdens and improving patient care. However, stakeholders from disparate sectors held reservations about digital intervention and had different views on the best approaches to supporting PA among older adults. This discord was exacerbated by conflicts with existing local initiatives, such as group exercise programs, which occasionally hindered the implementation of Active Lives. Furthermore, bureaucratic hurdles within National Health Service trust approval processes acted as formidable obstacles, dampening progress and resolve, highlighting the need for guidance in identifying sustainable and scalable practices.Conclusions: the findings highlight important implementation challenges to digital PA interventions for older adults such as bureaucratic barriers and alignment with ongoing initiatives. This research emphasizes the necessity for strategic direction and multilevel guidance to efficiently implement digital interventions for PA among community-dwelling older adults
Proportions of basement membrane proteins in cerebrovascular smooth muscle cells after exposure to hypercapnia and amyloid beta
No full textVascular basement membranes (BMs), composed of laminins, collagen IV, fibronectin, and perlecan, are secreted by endothelial cells, pericytes, smooth muscle cells (SMCs), and astrocytes. In the brain, amyloid beta (Aβ) is eliminated along cerebrovascular BMs of capillaries and arteries as intramural periarterial drainage (IPAD). Ageing modifies vascular BMs, impairing IPAD and leading to Aβ deposition as cerebral amyloid angiopathy. To better understand the molecular determinants of IPAD in ageing, we quantified the relative abundance of BMs secreted by human-derived cerebral endothelial cells, pericytes, brain vascular SMCs, and astrocytes in vitro. We then assessed BM protein levels in SMCs under hypercapnia (8% CO 2) as a model of vascular ageing, with and without Aβ exposure. Of the four cell types, we found SMCs secreted the highest levels of fibronectin, laminin, and perlecan, whilst pericytes secreted the highest levels of collagen IV. Hypercapnia increased the expression of collagen IV and fibronectin in SMCs but decreased the expression of laminin. The expression of perlecan increased under hypercapnia, but only in the presence of Aβ. This work highlights the varying compositions of vascular BMs and the dynamic differential responses of SMCs to Aβ and hypercapnia, helping to elucidate the age-related changes that impair IPAD in cerebral vessels. </p
Understanding the causes of crime amongst the 'Bayaaye' of Kampala-Uganda: The role of context
No full textTheories of crime have focused almost exclusively on research, data and ideas generated by global north sociologists. This has led to a focus on the problem of crime as it manifests itself in America and Europe. The philosopher Richard Rorty refers to this as the "conversation of the West" (Bernstein J, 2008). This conversation and intellectual context have largely shaped both the method and focus of criminology. Problems however arise when research findings are generalised to non-western settings. Bayaaye is a general term that refers to a group of young people in Kampala (Uganda); who are ‘common criminals’. To a large extent Uganda did not experience the contexts that generated western data and theory. The cultural experiences, modes of transition into adulthood, routines and socialisation spaces of young people in Uganda, substantially differ from those of the global north. Using an ethnographic approach, this study explored the causes of criminality amongst the Bayaaye within their unique ‘Kampala markets’ context. By examining the contexts that gave rise to current criminological theories, the study tries to determine their relevance with regard to the Bayaaye. A sample of 105 Bayaaye was chosen for the study using a snowball approach. Responses from a final cohort of 65 respondents were considered and analysed. Historical works of criminology were examined as a basis for the analysis and interpretation of results.<br/
Development and Application of Grand Canonical Nonequilibrium Candidate Monte Carlo for in silico Prediction of Fragment Binding Sites, Modes, and Affinities
No full textStructure and fragment-based drug design are increasingly popular approaches to drug discovery. Computational tools have become integral to these campaigns and provide a route to library design, virtual screening, property prediction, identifying putative binding sites, elucidating binding geometries, and predicting accurate binding affinities. This thesis discusses various molecular simulation methods and assesses their applicability to these drug discovery regimes. Molecular dynamics-based simulations are a useful tool in computer-aided drug design but are often limited by sampling issues related to the simulation timescales obtainable. Here, we develop, implement, validate, and test the application of grand canonical nonequilibrium candidate Monte Carlo (GCNCMC) to accurately predict the binding sites, modes, and affinities of fragment-like molecules. To this end, we develop the Python module, grandlig. GCNCMC simulations can accurately predict the location of small molecules in protein-ligand systems by attempting the insertion and deletion of molecules to, or from, a region of interest; each proposed move is subject to a rigorous acceptance test based on the thermodynamic properties of the system. We first set the scene and highlight the limitations of basic MD simulations by applying a variety of methods to the ERK2 protein. The theory and development of ligand-based GCNCMC is then presented with a rigorous validation of the method. The subsequent chapters then present various ways in which GCNCMC can be used to enhance the drug discovery pipeline by applying the method to two protein-ligand systems, T4L99A and MUP1. We demonstrate the ability of fragment-based GCNCMC to rapidly and reliably find experimental fragment binding sites, show that the method can accurately sample multiple fragment binding modes without any prior knowledge of their existence, and finally demonstrate the method's ability as a free energy estimator. We present two novel applications of GCNCMC; the integration of GCNCMC into mixed solvent MD, a popular method for binding site identification, and as a fragment screening tool. In both cases, we observe promising results and outline steps for the future which could make this method a powerful tool in the computational-aided drug design arsenal
Working from home: is it changing where we live?
No full textWorking from home has become more common, especially among graduates and those in high-skilled roles. While this might be expected to free households to move to new locations, our research finds that, while working from home is one of several complex factors in residential mobility, it has not, so far, played a major role in changing where people live. Decisions about moving are still mainly influenced by factors like age, relationship status, and housing. This briefing looks at what drives mobility among high-skilled workers and what it means for tackling regional inequalities and boosting economic growth across the UK
Analysis of thermodiffusive instabilities in hydrogen/air premixed flames using a tabulated flamelet model
No full textIn this work, a comprehensive formulation including detailed transport effects through mixture-averaged molecular diffusion in the context of tabulated chemistry is applied to the study of the propagation and structure of freely propagating hydrogen flames where intrinsic instabilities play an important role. The performance of the tabulated approach is evaluated by comparing its predictions with those from detailed chemistry calculations. The analysis focuses on two key aspects: the model's behaviour in both linear and non-linear regimes, and its sensitivity to pressure and temperature variations. Additionally, the impact of mesh resolution on the flame response is examined to assess the capabilities of the proposed method to recover the fundamental aspects of the flames. The analysis begins by examining the linear regime through the dispersion relation. The results indicate that thermodynamic conditions significantly influence the wavenumber range predicted by the tabulated model. Specifically, increasing temperature or pressure extends the model's predictive capability—either by reducing flame instability (at higher temperature) or by producing a thinner flame front (at higher pressure). However, some discrepancies in the dispersion relation within the linear regime, particularly for the stable range, are observed, revealing a slight tendency of the tabulated model to overpredict flame wrinkling. Subsequently, the non-linear regime is analysed by computing global flame parameters and comparing the flame structure with the reference solutions. The results show that the model accurately captures global flame descriptors for the three conditions investigated with relative errors of less than 10%. Considering the complexity of the physical and chemical phenomena involved, it can be concluded that the model successfully reproduces the most relevant effects governing flames exhibiting thermodiffusive instabilities and offers a reliable alternative to detailed chemistry with notably lower computational cost. Novelty and significance statement This research work contributes to delimiting the capabilities of a new formulation for a flamelet tabulated method that includes preferential diffusion through mixture-averaged diffusion to predict intrinsic instabilities in premixed hydrogen flames. To this end, several operating conditions are simulated to understand the influence of pressure and temperature on the accuracy of the model's response. The linear and non-linear regimes are studied and compared with the detailed chemistry solutions to provide an integral description. The novelty of this investigation lies in the demonstration that such formulation can recover significant characteristics of the flame that exhibits thermodiffusive instabilities for representative operating conditions.</p
Cultural Strategies Dataset
No full textThis dataset is part of the Cultural Strategies Think Kit and was created by Professor Dan Ashton, Dr Makanani Bell and Dr Joey Jones at the University of Southampton.To access the dataset use the https://download.culturalstrategies.soton.ac.uk/ link below.For information on search methodology, please see Introduction to the Cultural Strategies in England database, https://doi.org/10.5258/SOTON/P1121<br/
A synthetic investigation into the biosynthesis of hypsampsone A
No full textA simplified proposal for the biogenetic origin of hypsampsone A, a complex meroterpenoid, is supported by a bioinspired cascade reaction that rapidly assembles its polycyclic core. The key steps in both the proposed biosynthesis and the bioinspired cascade are a spontaneous intramolecular carbonyl-ene reaction, an α-hydroxy- β-diketone rearrangement and a terminating intramolecular aldol reaction. The feasibility of this model cascade reaction strongly suggests that hypsampsone A is a highly rearranged member of the polycyclic polyprenylated acylphloroglucinol (PPAP) family of natural products
Self-supervised learning with multimodal remote sensed maps for seafloor visual class inference
No full textSeafloor surveys often gather multiple modes of remote sensed mapping and sampling data to infer kilo- to mega-hectare scale seafloor habitat distributions. However, efforts to extract information from multimodal data are complicated by inconsistencies between measurement modes (e.g., resolution, positional offsets, geometric distortions) and different acquisition periods for dynamically changing environments. In this study, we investigate the use of location information during multimodal feature learning and its impact on habitat classification. Experiments on multimodal datasets gathered from three Marine Protected Areas (MPAs) showed improved robustness and performance when using location-based regularisation terms compared to equivalent autoencoder-based and contrastive self-supervised feature learners. Location-guiding improved F1 scores by 7.7% for autoencoder-based and 28.8% for contrastive feature learners averaged across 78 experiments on datasets spanning three distinct sites and 18 data modes. Location-guiding enhances performance when combining multimodal data, increasing F1 scores by an average of 8.8% and 37.8% compared to the best-performing individual mode being combined for autoencoder-based and contrastive self-supervised models, respectively. Performance gains are maintained over a large range of location-guiding distance hyperparameters, where improvements of 5.3% and 29.4% are achieved on average over an order-of-magnitude range of hyperparameters for the autoencoder and contrastive learners, respectively, both comparing favourably with optimally tuned conditions. Location-guiding also exhibits robustness to position inconsistencies between combined data modes, still achieving an average of 3.0% and 30.4% increase in performance compared to equivalent feature learners without location regularisation when position offsets of up to 10 m are artificially introduced to the remote sensed data. Our results show that the classifier used to delineate the learned feature spaces has less impact on performance than the feature learner, with probabilistic classifiers averaging 3.4% higher F1 scores than non-probabilistic classifiers
Cosmetic gatekeepers: Negotiations of beauty and (re)shaping bodies by medical aesthetic practitioners
No full textAesthetic practitioners who administer (non-)surgical medical cosmetic procedures play a central, and growing, role in the (re)shaping of predominantly women's bodies. This article focuses on how these practitioners negotiate their role as cosmetic gatekeepers – those with the medical and sociocultural skills, knowledge and tools - in (re)shaping the bodies of their client-patients. Adopting a reflexive thematic analysis of interviews conducted with aesthetic practitioners in the UK and the Netherlands, we identify three main themes. The first theme, conceptualizing beauty, describes the different ways in which aesthetic practitioners describe and negotiate the concept of ‘beauty’, including discussions of beauty as both subjective and objective. The second theme, shaping bodies, explores how practitioners consider why and how they (do not) suggest aesthetic procedures and how they (do not) see themselves as significant shapers of bodies and beauty. Finally, the theme of cosmetic gatekeepers examines the ways in which aesthetic practitioners provide boundaries in terms of how, when, why and on whom they (do not) perform procedures. Inherent to these discussions are constructions of the (non-)surgical ‘other’ and tensions between commercialism and ‘medico-cosmetic’ considerations that must be navigated by aesthetic practitioners. This article furthers explorations of how certain aesthetic appearances are (re)produced as desirable in increasingly expansive, diversified and normalized (non-)surgical cosmetic servicescapes
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