VictorJuiz/thesis huggingface dataset:
Targeting alarmins to accelerate healing

Promoting tissue repair in adults represents a major unmet medical need. Tissue regeneration relies on the activation of quiescent endogenous stem cells and whilst considerable progress has been made, novel therapies based on stem cells have thus far failed to translate to routine clinical practice. Much attention has focussed on administrating exogenous stem cells expanded or altered in vitro. However, this approach faces several major limitations, including poor engraftment, high cost and importantly, the necessity for immunosuppression for allogenic cells. An alternative strategy that overcomes these shortcomings is to promote repair by harnessing the regenerative potential of endogenous stem cells. This thesis focussed on the role of alarmins, the upstream group of mediators released immediately following injury, in promoting tissue regeneration. I show that the alarmin HMGB1 accelerates tissue regeneration in various systems by transitioning multiple stem cell types from the quiescent G0 to the GAlert state. Firstly, in vitro screening of candidate alarmins with human bone marrow-derived mesenchymal stromal cells showed that only pre-treatment with HMGB1 improved osteogenic differentiation. Using an optimised murine fracture model, I found that local administration of HMGB1 accelerated bone regeneration via the CXCL12-CXCR4 axis, whilst healing was impaired in inducible Hmgb1-/- animals. Cell cycle analyses revealed that HMGB1 transitioned the skeletal stem cell from G0 to GAlert. In this intermediate phase, the cell is more metabolically active and efficiently enters the cell cycle when exposed to activating factors. This effect also extended to other types of stem cells, including murine haematopoietic and muscle stem cells, as well as human haematopoietic stem and progenitor cells, and MSCs. Using murine models, HMGB1 accelerated recovery from injury to these tissues. Finally, treatment with a single systemic dose of HMGB1 two weeks before injury also accelerated bone, haematopoietic, and muscle regeneration, which was indicative of an acquired pro-regenerative signature. These findings document that the HMGB1-GAlert pathway results in a dynamic and adaptive multi-tissue regenerative response, and suggest that exogenous HMGB1 may be of therapeutic benefit in diverse clinical contexts, including trauma, chemotherapy, and elective surgery.

Keywords: Stem cells
Fracture
Cell cycle
Immunology
Tissue regeneration
Advisor: Chan, J
Horwood, N
Nanchahal, J
Passive acoustic mapping for improved detection and localisation of cavitation activity

Passive acoustic mapping (PAM) is a novel method for monitoring ultrasound therapies by mapping sources of acoustic activity, and in most cases cavitation activity, using an array of detectors. Although the range of its applications is indicative of its great potential, clinical adoption is currently hindered by its limited spatial resolution and the inherent difficulty of distinguishing, at depth, between nonlinear signals arising from nonlinear propagation and those arising from processes such as cavitation. The objective of this thesis is to address this limitation, by improving both the detection of the signal-of-interest and the source localisation.
An optimum data-adaptive array beamforming algorithm is proposed, Robust Beamforming by Linear Programming (RLPB), which exploits the higher-orderstatistics of the recorded signals, aiming at improving PAM source localisation. Both simulations and in vitro experimentation demonstrated improvement in PAM spatial resolution compared to a previously introduced algorithm, Robust Capon Beamformer. More specifically, under the in vitro conditions examined here, a 22% and 14% increase in the axial and transverse PAM resolution is respectively achieved.
In terms of reliable signal-of-interest detection amongst interfering signals, a time-domain data-adaptive parametric model, Sum-of-Harmonics (SOH) model, is developed. This model enables accurate estimation of time-varying-amplitude narrowband components in the presence of broadband signals. Respectively, it can recover a weak broadband signal in the presence of a dominant narrowband component. Compared to conventional comb filtering, SOH model enables PAM of cavitation sources that better reflect their physical location and extent.
PAM performance enhancement achieved by combining the proposed beamforming and filtering approaches is assessed in a context where spatial resolution really matters, namely for distinguishing between cavitation activity occurring inside a channel and perivascularly following cavitation-mediated extravasation. Adoption of the proposed method results in more accurate isolation of the broadband emissions from inertially cavitating sources, and more reliable localisation of these sources despite the long source-to-array distance has been observed. Such an improvement to the spatial accuracy of PAM paves the way towards its clinical translation, and in vivo experimentation is the next step for further validation of PAM in conjunction with the proposed methods under clinically relevant conditions.

Advisor: Coussios, C
Quality of life, social interaction and cognitive stimulation therapy: understanding the perspectives of people with dementia and their carers

Dementia is a progressive condition that can profoundly affect the lives of individuals and their families. With no known cure for the disease, the focus has shifted towards promoting well-being and enabling individuals to maintain an optimum quality of life. Understanding of the perspectives of both people with dementia and their carers in this area will provide greater insight into to the provision of dementia care services.
The first paper systematically reviewed the literature exploring the level of agreement between self and family-proxy ratings of patient quality of life. Twenty-six studies were identified for review. The overall level of agreement between ratings was low. Patients were found to consistently rate their quality of life as higher, compared to family-proxy ratings. A range of factors influencing this discrepancy were identified: neuropsychiatric symptoms, cognition, awareness of disease, caregiver burden and stress, relationship factors, activities of daily living and sociodemographic characteristics. The need for further interventions to address these factors is highlighted, as well as implications for future research.
The second paper aimed to explore people with dementia and their carers lived experience of social interaction and communication after attending a Cognitive Stimulation Therapy (CST) group. Interpretative Phenomenological Analysis revealed six superordinate themes. These captured the difficulties faced by people with dementia in accessing social opportunities and the positive experience of being in the CST group. Several challenges experienced by carers were highlighted and the subsequent impact this had on their emotional well-being. Improvements for people with dementia were noticed in areas of social communication, confidence and emotional wellbeing, with no noticeable change in memory. Carers expressed a desire for on-going support and intervention following the group. These findings have important implications for future research, dementia care and increased carer support.

Keywords: Dementia
cognitive stimulation therapy
Quality of life
Advisor: Fossey, J
Helping "us" vs. "them": ingroup favouritism in prosocial behaviour

To what extent is the tendency to act more prosocially towards ingroup than outgroup members a 'default' tendency that is based on intuitive processes activated across different social contexts and with different social groups? Here I report three sets of targeted empirical studies that use economic games to explore ingroup favouritism in prosocial behaviour. In Chapter 2, I use a newly developed measure to explore whether simply categorizing people into groups is sufficient to induce ingroup favouritism in both gains and losses frames. I find that minimal groups are significantly more prosocial to ingroup members than outgroup members, regardless of the economic cost of helping, whether decisions were public or private, and whether the decision is framed in terms of gains and losses. In Chapter 3 I apply dual-process models to intergroup prosocial behaviour and show that even under time pressure without the potential to deliberate, participants cooperate more with minimal ingroup than outgroup members in both gains and losses frames. In Chapter 4, I explore ingroup favouritism in the context of real religious groups using games that either have (Trust Game) or lack (Dictator Game) interdependent outcomes. I find ingroup favouritism only by atheist participants in a Dictator Game. In both games, Christian participants transferred more to both Christian and atheist recipients, and this was driven by the frequency of thinking about religious ideas. Together, my results support the thesis that ingroup favouritism is a default, intuitive, tendency robust across different contexts and even with novel groups, and charts a course for future research.

Advisor: Hewstone, M
Crockett, M
Faber, N
Does the use of the Internet further democratic participation? A comparison of citizens' interactions with political representatives in the UK and Germany

This thesis explores the implications of the Internet for democracy, re-evaluating the various claims and counter-claims that have been made for the Internet's democratic potential. Based on a framework to measure democracy that emphasises popular control and political equality, it assesses whether the Internet gives a greater and more representative share of the population the opportunity to participate in the political process by focusing on use of the Internet to contact political representatives. The analysis combines secondary analysis of population surveys with original data collected in two online surveys from more than 14,000 users of successful contact facilitation platforms in the UK (WriteToThem.com) and Germany (Abgeordnetenwatch.de) that enable sending messages to representatives.
The results show that in both countries the Internet in general has only marginally increased the number of people engaged in contacting. At the same time, contact facilitation platforms as specific online applications have attracted large numbers of people who have never before contacted a representative. While all online means of contacting primarily amplify traditional participatory biases, such as for gender and education, they can at least selectively engage traditionally under-represented parts of the population, for example young people or low-income groups. The processes that shape these patterns are identified by developing a basic theory of contacting and using the similarities and differences between the findings for the two countries. It demonstrates not only that participation continues to be dominated by traditional determinants that cannot be completely overcome by technology, but also that Internet applications can shape participation patterns – if designed to appropriately adapt to the context in which they operate, which is rarely the case. This highlights the need to think carefully about how online platforms can be used, building on the – albeit limited – gains identified here, to strengthen them as a means of ensuring democratic participation.

Keywords: WriteToThem
Abgeordnetenwatch
online participation
political participation
Advisor: Schroeder, R
Margetts, H
Perspectives on recovery and recall to hospital in forensic mental health

People who are mentally unwell and have committed a criminal offence are cared for by forensic mental health services. Their treatment is provided in secure hospitals so that any risks to the public are minimised. The complex nature of the mental health difficulties experienced by this clinical population means that they are typically treated in secure hospitals for several years, incurring high economic and personal costs. The need for meaningful approaches to treatment and management of these individuals is therefore paramount. The first paper systematically reviewed eighteen qualitative research papers that explored stakeholder perspectives on the personal recovery approach to care in forensic contexts. Principles of personal recovery were perceived to be meaningful and applicable in forensic contexts if adaptations were made to overcome inherent barriers such as restrictions due to risk management. Methodological quality of the reviewed studies was limited by shortcomings in the transparency of study procedures. The second paper explored the experiences of a significant subpopulation of forensic service users who were discharged to the community subject to conditions including ongoing monitoring, then recalled back to a secure hospital due to a relapse in their mental state or other indicators of increased risk. Using grounded theory, a theoretical model was developed of how these individuals make sense of being recalled. This was found to be a recursive process influenced by their perceptions of events before their recall, during the recall itself, and their subsequent experiences.

Keywords: Qualitative research
Forensic mental health
Advisor: Churchman, C
Harrison, S
Couldrey, C
Improving the clinical understanding and measurement of dissociation

'Dissociation' describes a range of anomalous perceptual, cognitive and affective experiences that occur transdiagnostically. Examples include mental blanks, and feeling 'unreal'. Whilst its ubiquity is becoming accepted by clinicians, there is currently little understanding of the mechanistic role played by dissociation in clinically important presentations. The present thesis addresses this gap in two ways: by establishing the role dissociation plays in a key clinical presentation (youth deliberate self-harm; [DSH]), and by offering an updated measure of dissociation for use in future research.
In Paper A, a review of nineteen eligible studies found an association between deliberate self-harm and dissociation, with more severe dissociation associated with more severe DSH, DSH in more locations on the body, and use of multiple methods of DSH. However, the review was unable to conclusively determine the direction of the association, largely due to limitations in studies' research designs.
In Paper B, the development and psychometric properties of a new, clinically useful and up-to-date measure of dissociation are described. Clinician and service user consultation were used in the early stages to ensure a comprehensive representation of dissociative experiences. The result is a measure with five subscales with good validity and reliability. Suggestions for further validation of the measure are also made.

Advisor: Cooper, M
Chan, C
Effect of elevated glucose on primary human tenocytes and implications for diabetic tendinopathy

Diabetes mellitus (DM) is associated with a variety of musculoskeletal manifestations, including tendinopathy. The incidence of tendon disease in DM patients is increased compared to the general population, suggesting that tendon is a tissue sensitive to elevated blood glucose. Furthermore, it has been shown that chronic high blood glucose levels cause damage to cells in several ways, including increased oxidative stress. Therefore cellular responses of in vitro primary human tenocytes to a range of chronic glucose conditions (5, 17 and 30 mM) were investigated. Additionally, cells were also exposed to H2O2. Streptozotocin-induced type I diabetic (T1D) rats were used to evaluate in vivo changes.
First, tenocyte physiology exhibited changes in multiple aspects in response to ele- vated glucose concentration. Gene expression of collagen, asporin, biglycan and aggrecan was upregulated in 17 mM glucose condition. Data further indicated that SOD-2 was markedly increased in response to elevated glucose (12-fold increase in 17 mM glucose and 5-fold increase in 30 mM glucose, both compared to 5 mM glucose control). Immuno- histochemistry on T1D rats indicated that skeletal muscle tissue was 3NT-positive to a high degree in diabetic condition compared to control.
Second, oxidative stress was induced in primary human tenocyes by H2O2 treatment. Extracellular glucose affected cellular response to H2O2: 1 mM H2O2-treated tenocytes in high glucose media had cell metabolic activity significantly decreased compared to iden- tical H2O2 treatment in low glucose media. Furthermore, acute treatment with glucose identified that even short (72 h) bursts of elevated glucose can aggravate the response of cells to H2O2. A panel of protective agents was tested; N-acetylcysteine was the sole treat- ment that proved to be effective to a certain degree. Overall, negative effects of H2O2 were more pronounced under elevated glucose condition in primary human tenocytes. Findings of this thesis provide a necessary fundamental insight into diabetic tendon problems and may inform the development of new clinical treatments.

Advisor: Hulley, P
Thompson, M
Domestic interiors: gender, ethics, and friendship in Jordan

This thesis draws on 34 months of participant observation in a working-class neighborhood of Amman, Jordan to ask whether and how gender, specifically femininity, can serve as a framework for ethical self-cultivation. It describes the relationships between morality, progress, and gender in contemporary Jordan, where progress is viewed as important and inevitable but also amoral, and morality is associated with the past, which is the opposite of progress. Women are uniquely affected by these oppositions because they are expected to both preserve the morality of the past and embody progress, defined as maximizing their own self-interest through consumption, education, employment, and participation in public life.
In this confounding context, women must be deliberate about how they choose to define and inhabit proper femininity, and the work of defining and inhabiting demands creative and productive engagement on their part. They respond by participating in a bounded public that not everyone can enter, and by making and maintaining a distinct temporality inside their homes that is distinguished from the temporality of urban life outside the home. They observe and work on their bodies in a complex and highly elaborated way, differentiating intuitive knowledge (authentic) from social knowledge (instrumental) and biological (medicalized), and they approach friendship as an arena for establishing boundaries between oneself and others, and for dealing with the social ramifications of the individualized approach to self-cultivation that is available to them.

Keywords: Gender
Ethics
Jordan
Advisor: Clarke, M
Parkin, R
Implied licences in copyright law

Copyright licences can be implied when the doing of a restricted act is covered neither by the express licence of the copyright owner, nor by one of the statutory limitations and exceptions. The manner in which copyright licences are implied, therefore, holds the key to broadening the scope of permissible acts. In contrast to the rigidity of statutory limitations and exceptions, implied licences are more malleable in being able to respond to a diverse set of circumstances, as the need arises. Thus, implied licences can serve as a flexible and targeted mechanism to balance competing interests, including those of copyright owners and content users, especially in today’s dynamic technological environment. However, implication as a process is contentious, and there are no established rules for implying a licence. Implication of a copyright licence is even more complicated because the conceptualisation of a copyright licence is unsatisfactory. The resulting uncertainty has prevented implied licences from being embraced more readily by the courts. The objective of this thesis is, therefore, firstly, to reconceptualise a copyright licence that is broad enough to accommodate the diverse circumstances in which copyright licences arise, and certain enough to assist in finding their constituents; secondly, to propose frameworks for implying copyright licences in a methodical and transparent manner, based on three sources: the consent of the copyright owner; an established custom; and state intervention to achieve public policy goals. The frameworks are also customised differently for implied bare and implied contractual licences. The thesis demonstrates the robustness of these frameworks by rationalising them with the existing case law. Underscoring the contemporary relevance of implied licences, in conclusion, the thesis tests and validates the frameworks in relation to three essential and ubiquitous functions on the internet – browsing, hyperlinking and indexing.

Keywords: Copyright Law
Implied License
Implied Licence
Advisor: Dinwoodie, G
Omnifarious octocoral observations: ecology and genetics of octocoral communities from Útila, Bay Islands, Honduras

The Oxford English Dictionary defines 'omnifarious' as 'comprising or relating to all sorts or varieties', which quite accurately captures the very nature of octocorals and this thesis. The research reported here, aims to describe undocumented communities of coral reef organisms – the octocorals – which are an emergent dominant component within their threatened ecosystem of the Caribbean. Within the last four decades, coral reefs worldwide have experienced a precipitous plunge in many ecosystem services they provide, and most notably in the Caribbean. The foundation to reef resilience is structured on the ecosystem’s ability to repair and restructure itself in the face of environmental shifts. These intricately complex strategies of resilience depend on repair mechanisms provided by a source of biodiversity, much of which remains poorly understood. This work explores many facets of the functioning within this potential future coral reef ecosystem. These reports are one of the most significant contributions to documenting and describing octocoral biodiversity (e.g. species, genetic, and community diversity) of the wider ecoregion of the Mesoamerican Barrier Reef System within the last three decades.

Keywords: ALG11
diversity
mtmuts
octocoral
parasite
coral
ecology
Utila
habitat
host
COI
flamingo tongue snail
symbiosis
Cyphoma gibbous
phylogenetics
Caribbean
genetics
molecular
Mesoamerican Barrier Reef
biodiversity
Advisor: Rogers, A
Speight, M