The dance and diabetes project: an evolving model for engagement with underserved communities

The Dance and Diabetes project took place between 2017 and 2022, and utilised dance to engage South Asian women with diabetes research in Leicester. The rate of diabetes in the British South Asian population is about 20% higher than in White British population and manifests itself between 10-15 years earlier (Gholap et al 2011, Goff 2019). Reducing diabetes is a global priority (WHO 2016) and a particular concern for health and research services in Leicester where there is a large South Asian population. As such a project delivering engagement around diabetes was a strategic priority. The team assembled to deliver the project was multidisciplinary and included: Leicester Diabetes Centre (LDC), NIHR Leicester Biomedical Research Centre (BRC), University of Leicester (UoL), University Hospitals of Leicester NHS Trust (UHL), proximal research and NIHR infrastructure, Aakash Odedra Dance Company, Shiamak Midlands, Moving Together and the participating women. The project was developed over multiple cycles using Sagor’s (2011) model of action research. This entailed, for each stage of the project, clarifying our vision and targets, articulating a theory of action, implementing action and collecting data, and reflecting on the data to plan informed action (Sagor 2011). Whilst every stage featured assessment of impact, in the final cycle focus groups confirmed that participant perspective aligned with our assessment. Transcriptions were analysed using content analysis. Each cycle of action research served to establish credibility and trustworthiness of themes by referring back to existing theory and research, and incorporating new theory and research as it became relevant. The project rapidly and radically transformed. Early success encouraged the project team to greater aspiration. Ongoing impact assessment associated with the action research cycle indicated that the model had potential to impact health inequalities resulting in a refocus of the project on broader impacts. Situational factors, notably inability to source funds and restrictions associated with the COVID-19 pandemic also had a considerable impact on the direction and implementation of the project. The project saw participating women empowered to assume responsibility and authority within the project, taking on roles as organisers and influencers, running discussion sessions around areas of interest, conducting formal community consultations themselves as Community Researchers and even running the project in the absence of funding during the summer of 2019. The different cultures, skills and expertise of project partners established different ways of working, which necessitated consistent renegotiation and communication. Communication supported delivery; it also constructed and reconstructed our understanding of the project and its impacts, and supported the development of cultural competence between project partners. The project found consistent support for O’Mara Eves et als (2013) recommendations for conduct of community engagement, particularly regards a culturally specific approach and relationship building. Dance, owing to its culturally specific nature and potential to create feelings of cohesion (Lakens and Shel 2011, Hove and Risen 2009, Miles Lind and McCrae 2009), was an effective tool to achieve this. The themes identified also reflected the domains identified by Sung et al (2013) as determinants of effective community engagement (flexibility, a sense of belonging, commitment, communication, being genuine, relevance, sustainability). The impact assessment for the project supports assertions that high-quality community engagement can impact health inequalities and provides examples of social justice in action

Visualising prison violence: exploring the micro-dynamics of violence in men's prisons using video data

The present thesis presents an exploratory study in the field of prison violence. Until recently, most research on physical violence, both in and outside of prison, has been concerned with background and causal factors as well as social and structural contexts, leaving out the actual moments of violent action. A novel research trend, Visual Data Analysis (VDA), emerging from one of the major theories of violence of recent times (Collins, 2008), draws on photos and video footage to shift the focus towards interactions and behaviour observable in violent incidents. The VDA method allows for studying the micro-dynamics of physical violence by means of video-footage. Employing CCTV and mobile device-footage of violent incidents from YouTube as empirical material in combination with focus group interviews with current prison officers and ex-prisoners, the thesis contributes to the micro-sociology of violence, particularly prison violence, by examining the strengths and limitations of video data sampled online - as a general method as well as in the specific context of prison violence research - thus addressing a gap in the field of VDA research. At the same time, it tests the applicability of Collins’ theory of violence to the prison setting, i.e., to a non-public context to which it has not previously been applied. By analysing interactional processes and expressions of emotion and discussing interpretations of these with individuals familiar with the prison setting, the thesis finds that audiences in prisoner-on-prisoner fights regulate both the severity and the course of the fights; where (co-prisoner) audiences exhibit enthusiasm through cheers and encouragements, fights are prolonged, a finding which echoes Collins’ (2008) observations of audience impact. The analysis further suggests that prison officers who exhibit anger or aggression through shouting, giving orders, or by invading prisoners' personal space provoke prisoners to exhibit similar behaviours or to use violence against the officers. Lastly, the study also shows that officers who exhibit fear through struggles to control bodily movements allow prisoners to take charge of the course of interaction, i.e., to gain or maintain emotional dominance, and to use violence, a dynamic resonating with Collins’ (2008) notion of how violent interactions are initiated. Based on the findings, the thesis is able to present implications of technical features for future video research drawing on online-sampled data, thus contributing to a furthering of the VDA method. The findings have also laid a foundation for (indicative) practical suggestions for prison officer training based on both Collins’ micro-dynamic approach and the VDA method. This highlights the potential of using video recordings of real-life incidents in the design of this type of training. The thesis concludes that Collins’ theory holds promising potential in furthering the understanding of the dynamics of (especially) escalation and de-escalation of potentially violent encounters – with or without the presence of audiences - between prisoners and between officers and prisoners, and thus for future development in the field of violence prevention and intervention in the prison context

Leveller social networks and their sectarian dynamic: 1646-1658

This thesis re-examines the so-called ‘Levellers’ of the English Revolutionary period alongside concurrent sectarian activity. The period under examination is the years 1646 to 1658, commencing with the gradual emergence of Leveller rhetoric from within London’s tolerationist discourse, and ending with the death of Oliver Cromwell in 1658, which commenced a period of recalibration and unrest across the Protectorate. The thesis argues that there was very little of what could be considered a distinct political Leveller movement, as previous scholarship has suggested, rather that Leveller networks and discourse existed within sectarian circles across the nation. It is argued that the nature of Leveller activity was far more dependent on a godly belief system and discourse within sectarian congregations than has previously been acknowledged. Rather than the traditional Leveller leadership, this work foregrounds sectarian preachers and polemicists, and it is argued that the Leveller platform was dependent on preachers and congregational circles as its primary means of development. Individuals such as Samual Oates, Samuel Chidley, Samuel Hyland and Jeremiah Ives are presented along with others as lay-preachers who were crucial nodes for driving Leveller activity. The thesis suggests that a Christian underpinning of Leveller beliefs, such as Right Reason, or an emphasis on godly righteousness, have been overlooked in previous scholarship and that these are further signals of a fundamentally Christian foundation to Leveller arguments. While a Reformed two-kingdoms theory, the separation of the civil and spiritual state, was at the heart of Leveller campaigns, issues of a democratic legislature rarely featured. This thesis demonstrates that Leveller arguments which were found in both civilian and military circles often employed a millenarian position, relating to the anticipated Second Coming, and much of their Christian belief informed their desires for an egalitarian and tolerationist civil government. This thesis will utilise the language of social networks in their informal exploration, suggesting that Levellersim is best understood as moving through a series of interwoven networks, rather than a coherent and organised movement. A social network vocabulary is utilised to assist in the understanding of Leveller social connections and the ways in which Leveller arguments were transmitted among godly congregations and social affiliations. After re-examining the period of Leveller activity most discussed in previous scholarship, the period 1646 to 1649, the thesis continues its analysis of ongoing sectarian Leveller activity into the Commonwealth and Protectorate years. This thesis concludes by examining the presence of Leveller arguments and social networks within Fifth Monarchist congregations, suggesting that the two persuasions need not have always been mutually exclusive. Some ministers and polemicists within the Fifth Monarchy community, including John Rogers, Samuel Hyland and James Frese did promote Leveller ideas as a godly position in preparation for the rule of Christ’s directly appointed Saints

A holistic kinetic model for the hydrothermal carbonisation of lignocellulosic biomass

This research presents the first holistic kinetic model for hydrothermal carbonisation (HTC) of lignocellulosic biomass, based on the composition of cellulose, hemicellulose, and lignin. The model predicts product outcomes for hydrochar, gas and liquid residuals over a wide range of processing conditions: temperatures (200 – 260 °C), residence times (0 – 12 hours), and biomass-to-water ratios (1:4 to 1:50). Individual kinetic models for the macromolecular compounds were developed and validated with experimental data. The combination into a holistic model demonstrated accurate predictions of the solid phase (hydrochar), where 258 data points from 58 lignocellulosic biomass sources (49 different types, from 41 studies including this one) were processed. The accuracy of the holistic kinetic model was improved when considering the interaction effects between the macromolecular compounds in lignocellulosic biomass and by determining optimised distribution factors for the non-macromolecular fraction into the solid, liquid and gas phases. The finalised R^2 value for hydrochar was 0.966. Prediction of the gas phase was evaluated and a correlation determined, however, further developments with more experimental quantification of this phase is necessary to improve prediction capabilities, with the final model resulting in an R^2 of 0.120 for this phase. The finalised holistic kinetic model shows promise for predicting the hydrochar produced from several non-traditional lignocellulosic biomass types, presenting an advanced future application of this research

High precision tools for intraoperative brain cancer therapy

Glioblastoma remains to be the most aggressive brain malignancy to affect adults. The disease has a median survival of only 15 months, owing to tumour recurrence within 2 cm of the primary tumour site. Despite the poor prognosis, standard treatment still relies heavily on surgical resection of the tumours, followed by chemotherapy with temozolomide and radiotherapy. This treatment is hindered by the vast heterogeneity within and between glioblastoma subtypes. In this work, the author has proposed the use of photodynamic therapy as an adjuvant to surgical resection. Photodynamic therapy utilises light to induce a reaction between a photosensitiser and molecular oxygen in order to initiate cell death. This technique centres on three main components; the photosensitiser, light and oxygen. Each of these, in themselves, are non-toxic and cell-death is only elicited when all three are combined. While there are promising candidates for the treatment of glioblastoma through photodynamic therapy, these photosensitisers are often bulky molecules which lack specific targeting groups. This results in side- and off-target effects as well as patient-dependent differences in dosage in the target tissues at the time of treatment. Therefore, a library of photosensitisers based on the nitrobenzoselenadiazole (SeNBD) scaffold was designed. By taking advantage of the low molecular weight of SeNBD, this photosensitiser was readily conjugated to other small molecules, with the overarching aim of targeting glioblastoma metabolism. While differential uptake of metabolites was not effective enough to discriminate between healthy and cancer tissue, a further level of control was added through the design of an activatable photosensitiser. This was achieved by disrupting the electron density within the scaffold, thus quenching the absorbance of the photosensitiser. The nature of these quenching groups can be altered to tune the stimulus which uncages the photosensitiser. As a result, a library of orthogonal and environmentally sensitive photosensitisers based on SeNBD has been created, and this approach applied to other photosensitive scaffolds (i.e. 2-thioxocoumarin, thionaphthalimide, Nile Blue and methylene blue). This highlights the modularity of the approach and the wider implication on developing activatable photodynamic therapy agents. Combining these two strategies paves the way to the development of some of the first enzyme activatable, metabolically targeted photosensitisers. As a model, a cathepsin B sensitive pro-fluorophore was synthesised based on the ONBD scaffold. Transcriptomic data from glioblastoma stem cells (GCGR-E17, GCGR-E31, GCGR-E57) and healthy foetal controls (GCGR-NS12ST_A, GCGR-NS17ST_A, GCGR-NS9FB_B) suggest that this approach can provide an effective route to selective ablation of glioblastoma cells without significant damage to surrounding healthy tissues

Using synthetic biology to understand DNA methylation maintenance in cancer

Loss of DNA methylation is common to the vast majority of human cancers and is considered a hallmark of cancer epigenomes. Current models propose that improper maintenance of DNA methylation could underpin this hypomethylation. However, these models are based on evidence derived from static snapshots of cancer methylomes. In addition, DNA methylation represents an important therapeutic target in cancer treatment. DNA hypomethylating agents (HMAs) are evidenced to promote antitumour immunity, however, existing HMAs have limited applications due to poor pharmacometrics and cytotoxicity. Thus, advancing our understanding of DNA hypomethylation in cancer, alongside identifying more effective drugs to target DNA methylation, is crucial for enhancing therapeutic strategies in cancer treatment. To gain insight into the dynamics of DNA methylation maintenance in colorectal cancer cells, I developed a methylation-sensitive reporter system. This piggyBac transposon-based system allows stable integration of a methylated eGFP transgene (eGFPme) at distinct locations across the genome. I show that methylation of this reporter construct represses its expression in colorectal cancer cells. Reporter integrations were identified across the whole genome, enabling tracking of genome-wide DNA methylation maintenance. To test whether HCT116 cells are able to faithfully propagate DNA methylation, cells containing premethylated reporters were maintained in culture for up to 8 weeks, equivalent to ~75 cell divisions. The majority of methylated reporters remained repressed and maintained their methylated status over this time course. These findings demonstrate that methylation patterns remain consistently preserved at synthetic reporters in HCT116 colorectal cancer cells. My results highlight the functionality of the DNA methylation maintenance machinery in colorectal cancer cells, despite the presence of extensive hypomethylation. Having demonstrated that DNA methylation is maintained in colorectal cancer cells, I next investigated the contribution of different components of the DNA methylation maintenance machinery to methylation maintenance. To do this, I assessed reporter activity in knock-out (KO) and degron cell lines. DNMT1 is the primary maintenance methyltransferase, responsible for maintaining DNA methylation following replication. As expected, reporter repression and methylation were not maintained in HCT116 cells lacking DNMT1 function. It has been previously reported that cooperation between DNMT1 and the de novo methyltransferase DNMT3B is required to maintain DNA methylation in mouse embryonic stem cells. However, this has not previously been tested in human cancer cells. To investigate the contribution of DNMT3B to DNA methylation maintenance, I assessed reporter activity in DNMT3BKO cells. No significant differences in reporter expression or methylation were detected in DNMT3BKO cells compared to HCT116. My results indicate that DNMT3B does not have a detectable contribution, in this experimental system, to methylation maintenance in human HCT116 cells. Next, I investigated the contribution of UHRF1 to DNA methylation maintenance. UHRF1 is an emerging therapeutic target of interest due to its essential role in DNA methylation maintenance, and its overexpression in some cancers. I integrated the eGFPme reporter into DNMT1 and UHRF1 degron cell lines. This degron system enables rapid depletion of the degron-tagged proteins, and I monitored reporter activity in response to protein depletion. Following DNMT1 or UHRF1 depletion, rapid upregulation of the reporter gene was detected. These results support that targeting UHRF1 is an efficient method to deplete DNA methylation colorectal cancer cells. Furthermore, these findings demonstrate that the reporter is activated in response to acute loss of DNA methylation. Finally, I sought to test whether the reporter system developed in this study could be utilised as a drug screening platform, to investigate compounds that modify DNA methylation. My previous results provided evidence for therapeutic targeting of DNMT1 and UHRF1. Therefore, I screened several novel inhibitors of DNMT1 and UHRF1. Removal of DNA methylation maintenance using the DNMT1 inhibitor GSK-3484862 resulted in a ~60% reduction of genome-wide methylation and rapid reporter activation. Importantly, I showed that GSK-3484862 treatment led to the activation of HERV-1 elements and IFN-1 signalling, which is thought to be important for the immunostimulatory applications of hypomethylating agents in cancer treatment. Together, my findings provide proof-of-concept for the use of this reporter system in large-scale compound library screen, to identify novel hypomethylating agents. The methylation-sensitive reporter system developed in this study was utilised to provide novel insights into the mechanisms underlying DNA methylation maintenance in cancer. This reporter system has future applications as a screening platform, to identify genetic factors involved in DNA methylation, and novel hypomethylating compounds with therapeutic potential

Sustaining the Post-Agreement Peace – Galkayo, Somalia

This policy brief draws on a forthcoming article which examines the dynamics of ‘post-agreement peace’ in Galkayo, Somalia, following the signing of the Galkayo ‘local’ agreement in 2017. It draws on previous research by the same study team, initially focused on the 2017 agreement and then on the conditions concerning its implementation. The brief draws attention to the need for adaptive, trans-scalar mediation work in relation to peacebuilding in multilayered conflicts, where peace must be continuously renegotiated across local, regional, and national arenas. It further situates Galkayo within Somalia’s broader political economy of peace and conflict, offering broader insights on the sustainability of peace in fragmented environments

Curvature statistics of turbulence

Turbulence is present in many different flow types across natural phenomena and industrial applications but still raises open questions due to its complexity and multi-scale nature which defers most direct analytical approaches. However, a statistical approach has proven itself as a powerful tool to help with the understanding and modelling of turbulence, overcoming some limitations of analytical approaches. Within this thesis, I analyse datasets of four different flow types, three of experimental nature and one of numerical nature to study the statistics of geometric quantities such as curvature and torsion, in particular concerning the effect of anisotropy. For the experimental datasets, the focus is on Lagrangian trajectories and for the numerical datasets on stream lines and, in case of a conducting fluid, magnetic field lines. These curves can be described as three-dimensional space curves and therefore curvature and torsion can give a full description of these. Curvature and torsion are particularly interesting measures of turbulence as a salient feature of turbulence is the presence of different spatial and temporal scales, which is captured by the different derivatives involved. The curvature vector is introduced as a new measure of the effect of anisotropies, originating from different mechanisms like a temperature gradient, mean flow or magnetic background field, on the geometry of Lagrangian trajectories and either stream lines or, in case of a conducting fluid, magnetic field lines. The first study includes Lagrangian experimental datasets of a turbulent von Kármán flow, Rayleigh-Bénard convection at two different Rayleigh numbers and the logarithmic layer of a turbulent zero-pressure-gradient boundary layer over a flat plate. The curvature and torsion statistics of von Kármán flow and Rayleigh-Bénard convection agree well with previously reported experimental and numerical results for the curvature and with numerical simulations of homogeneous and isotropic turbulence for the torsion. For the logarithmic region of the boundary layer, the form of the torsion probability density function (PDF) also agrees with these results. The curvature PDF retains the same heavy tail as curvature PDFs measured for the aforementioned flow types for small curvature events, however, high curvature events are suppressed by the mean flow. Studying the curvature vector and connecting it with velocity fluctuations shows the effect of anisotropy and allows a geometric interpretation of large-scale motion in terms of the structure of trajectories. In the second study, another type of anisotropy is introduced by a magnetic background field for a flow with electrically conducting fluid in magnetohydrodynamic turbulence. Utilising high resolution data obtained by direct numerical simulation of magnetohydrodynamic turbulence across a range of Reynolds numbers, the curvature PDFs of stream lines and magnetic field lines compare well with the PDFs derived based on Gaussian statistics for the Lagrangian trajectories. For the PDFs of the curvature vector components, the magnetic field lines tend to be less curved in the direction of the magnetic background field, which can be connected to the suppression of magnetic field fluctuations parallel to the magnetic background field and the partial two-dimensionalisation of the flow. The curvature vector PDFs of stream lines show that the effect of a magnetic background field on the geometry of stream lines is less profound compared to the effect on the magnetic field lines. The models mentioned above are based on Gaussian statistics. However, turbulence is more complex and intermittency plays a crucial role. As an improvement of these models, a model for the curvature PDF for von Kármán flow and Rayleigh-Bénard convection is derived, which takes spatio-temporal intermittency into account. Using a decomposition into Gaussian sub-ensembles, where within each the curvature PDF is known exactly, an exact model expression and a closed-form approximation for the curvature PDF can be derived. These PDFs agree qualitatively and quantitatively with the measured curvature PDFs of turbulent von Kármán flow and Rayleigh-Bénard convection

Predicting CO₂ migration in the shallow subsurface: the role of heterogeneity and mass transfer

Carbon capture and storage (CCS) is an important technology for the net-zero transition. The success of CCS relies on the security of storage, as unintended release of CO₂ from a storage site can impact water resources, release stored CO₂ to atmosphere and reduce the value of carbon credits associated with storage. Given the potential impacts, robust monitoring techniques are required, supported by a deep understanding of the complexities of CO₂ migration in the shallow subsurface. The objective of this research is to better understand the impacts of subsurface heterogeneity and multicomponent mass transfer on the fate and migration of CO₂ using numerical models. Simulations of a bench-scale CO₂ injection in saturated homogeneous sand were conducted using a coupled continuum-discrete approach using the Electrothermal Macroscopic Invasion Percolation (ET-MIP) model. ET-MIP was shown to accurately describe the experimental gas velocity, aqueous plume height and gas fingering behaviour, and demonstrated that multicomponent mass transfer impacts the persistence, distribution and development of the gas phase. A sensitivity study was conducted, and demonstrated that gas velocity and distribution were sensitive to the critical gas saturation and grid size. A binary tree algorithm was implemented for MIP including gas channel fragmentation and mobilization (MIP-FM) to improve performance of ET-MIP. The new algorithm showed a 76% decrease in overall run time when implemented in ET-MIP, and enables the use of ET-MIP in larger domains. Gas migration in realistic 3D sedimentary structures was simulated to understand the impact of cm-scale heterogeneities. Realistic sedimentary structures with cm-scale bedding and lamina were generated stochastically with varied entry pressure characteristics, and gas migration was simulated using MIP. The ensemble of gas migration results was analyzed and it was established that increased grain size contrast between the bedding and lamina (a function of both grain size and grain sorting of both materials) causes a transition from ganglia-dominated flow to pool-dominated flow and enhanced lateral migration from the source. These results highlight the challenges in gas migration monitoring, as small variations in heterogeneity can significantly alter gas migration pathways. Lastly, the effects of subscale heterogeneity, groundwater flow and gas composition on gas migration were investigated by simulating CO₂ and noble gas mixtures in heterogeneous domains with varied aqueous flow rates. Results showed that both heterogeneity and aqueous flow rate can influence the vertical migration of CO₂, as a significant portion of the CO₂ will dissolve. Additionally, dissolved noble gas ratios were shown to be sensitive to multicomponent mass transfer during injection and post-injection, as less soluble noble gases such as He will preferentially partition to the gaseous phase. The results of this thesis highlight the complexity of CO₂ migration in the shallow subsurface. Subscale heterogeneity can impact gas distribution, dissolution, and cause extensive lateral migration. Multicomponent mass transfer can impact the evolution of dissolved gas concentrations including noble gas ratios, and the persistence of gas in the subsurface. Ultimately, this research will help to improve monitoring and verification of CCS, through advancements in numerical modelling techniques and data interpretation. These findings extend beyond CCS, and can be applied to other fields of research including methane or hydrogen leakage and groundwater remediation techniques such as air-sparging or in-situ thermal remediation

Using theoretical physics to address complex dynamical problems in turbulence, geosciences and biology

Real-world systems are generally nonlinear, exhibiting complexity across a range of physical and temporal scales. In this thesis I tackle a series of real-world problems and questions which span the breadth of these different scales, from the microbiological to interplanetary. This is possible when each system is viewed from the perspective of theoretical physics as being reducible to the level of a dynamical system. Early on in my research, I realised that these approaches could be applied across many fields and chose to work in three of them. Turbulence remains one of the greatest challenges remaining in classical physics, and arises in our first dynamical system, the Navier-Stokes equations (NSEs). I investigate higher-dimensional versions of these equations using Direct Numerical Simulation studies to search for evidence of critical phenomena, using chaos as a measure. Using this together with a closure-approximated model, I investigate how increasing spatial dimensions appears to lead to a reduction in chaos, which might tentatively suggest a critical dimension of six for these equations. From the problem of turbulence, I turn to a related problem in ensemble numerical weather prediction, the signal-to-noise paradox. The paradox is that current ensemble systems seem to predict reality better than they predict themselves. By applying ergodic theory to ensemble forecasting, I show that using the ensemble mean as our best forecast of observations amounts to interpreting it as the most likely phase-space trajectory, which relies on the ergodic theorem. I argue that this fails in certain cases due to evidence of multi-modality, which can break the ergodic theorem, creating the paradox. Moving up a scale, the next problem I address is the practical challenge of contamination when trying to detect microbiology in Earth's upper atmosphere. Leveraging advances in aerospace technology, such as CubeSats and rocket-borne samplers, this research proposes a new technique called relative-velocity sampling, for capturing large particles in the understudied mesosphere and lower thermosphere. This technique reduces the contamination challenge to a simple one-dimensional dynamical system, obeying the NSEs. My ultimate problem lies on the largest scales where I apply the theory of island biogeography to interplanetary scales for planetary protection. This theory models population dynamics for inter-island populations and has been suggested as applicable to interplanetary systems. This is used to show that although such an equilibrium theory generally breaks down when applied to interplanetary scales, the mean-time to extinction resulting from the combined effects of growth and death rates can be quantified. This is used to challenge the probabilistic model of planetary protection and suggest how the mean-time to extinction can instead be used to assess colonisation risk. The broader applicability of island biogeography to considering biotic transfer at the interplanetary scale is considered. This thesis concludes with a synthesis of the problems tackled, illustrating the capability of theoretical physics to advance understanding in different fields underpinned by dynamical systems, and the role of interdisciplinary research