VictorJuiz/thesis huggingface dataset:
Novel approaches in optimising steatotic livers for transplantation

Normothermic machine perfusion (NMP) has the potential to transform liver transplantation by facilitating the safe and reliable transplantation of higher-risk livers, thereby reducing the number of waiting list deaths. However, it poses logistical challenges and the evidence to support its potential beneficial effects in steatotic livers remain to be elucidated in human studies. This thesis aims to investigate whether the preservation of steatotic livers can be enhanced by NMP resulting in improved post-transplant outcomes through a reduction in ischaemia-reperfusion injury (IRI) and by reducing the amount of intra-hepatic fat. I have demonstrated that static cold storage (SCS) prior to NMP is safe and feasible with comparable clinical outcomes and markers of graft injury to those in continuous NMP and significantly improved compared to SCS. This is likely to facilitate clinical adoption by improving logistics and reducing the cost. I have provided evidence to support NMP’s role in steatotic liver transplantation where early biochemical function is improved compared to cold stored steatotic livers. Furthermore, IRI characterised histologically and systemically is attenuated in steatotic NMP compared to SCS livers. Finally, I have demonstrated that in conjunction with de-fatting adjuncts, the ex situ function of steatotic livers can be improved and the amount of fat within the liver can be reduced by 45%. This is achieved through altering liver fat metabolism to favour improved/enhanced fatty acid oxidation with a concomitant reduction in de novo lipogenesis.

Advisor: Friend, P
Hodson, L
'Becoming adult in another man's land': the contested life projects of unaccompanied young migrant and refugee men negotiating pathways through welfare, asylum and immigration regimes in Europe

This thesis draws attention to a range of factors that influence why, how and when young migrant and refugee men engage with statutory and non-statutory sources of welfare and methods of immigration control as they ‘become adult’ in Europe. It does so through mixed methods qualitative research which took place over a period of 18 months in two cities in England and Italy. The four papers that constitute the body of the thesis draw on: critical policy-analysis; participatory research based in three support institutions; arts-based research conducted in collaboration with museums; and semi-structured interviews with unaccompanied young men, policy makers and practitioners. Read together, the papers raise fundamental questions pertaining to the ‘best interests’ of children and youth, and about how young migrant and refugee men engage with and understand welfare and the state as they pursue evolving plans and dreams in a context of increasing surveillance and immigration control. The thesis argues that unaccompanied young migrant men usually have clear – albeit malleable – ideas about the objective(s) of their migration. The European policy literature refers to such objectives as ‘life projects’. It is argued here that the life projects of young migrant and refugee men are poorly understood and this leads to a disconnect between the intentions and desires of the young people on the one hand and those of the various policy actors who seek to assist and/or govern them on the other. Several dimensions of the life projects of young migrant and refugee men are elucidated in this thesis. Among other findings, it suggests that they are inherently relational, shaped by the ideas of the young people in question and by those of their family members and social networks. They are also shown to be gendered and re-negotiated upon contact with a range of facilitating or hindering factors encountered upon arrival in Europe. Moreover, these life projects are rearticulated, renegotiated and reformed through the development and sharing of personal and collective narratives or stories.

Advisor: Bennett, F
Chatty, D
Chase, E
The scope of thermodynamics

This thesis investigates the application of the laws of thermodynamics to various sub-systems of the universe. I begin by distinguishing between three diﬀerent second laws: orthodox, statistical and probabilistic. After suggesting that entropy is best understood in means-relative terms, I then show that this interpretation does not imply an epistemic understanding of thermodynamics, pace Jaynes. I conclude the discussion of phenomenological thermodynamics by arguing that thermodynamics can properly be applied to systems containing only a single particle, given the right circumstances. Next I discuss thermodynamics in the context of black holes, and examine the question of whether black hole entropy is genuine thermodynamic entropy, as opposed merely to information-theoretic entropy. I examine the original arguments by Bekenstein and Hawking, and conclude that these are unsatisfactory, but I go on to demonstrate that black holes ought to be considered to be genuine thermodynamic objects by constructing a black hole Carnot cycle. The third chapter investigates thermodynamics in the quantum realm and begins by discussing a recent argument by Hemmo and Shenker against the identiﬁcation of the von Neumann entropy with the thermodynamic entropy. Their argument is shown to be ﬂawed as it a) allows for a violation of the second law and b) is based on an incorrect calculation of the entropy. I continue by providing a derivation of the laws of thermodynamics from quantum mechanics and a few phenomenological assumptions. This approach is then compared to so-called resource theories of thermodynamics and to single-shot thermodynamics. I end my discussion of quantum thermodynamics with the analysis of an argument made by Cabello et al., who claim that thermodynamics allows for the derivation of an empirical diﬀerence between two important classes of quantum interpretation. I provide a counterexample to this claim and show that the alleged heat cost is fully accounted for in the external agent.

Keywords: Black Hole Thermodynamics
Entropy
Philosophy of Physics
Quantum Thermodynamics
Thermodynamics
Advisor: Timpson, C
Brown, H
Maroney, O
Relationship between the gut microbiome and behaviour at the molecular, organism, population and evolutionary levels

Eukaryotes have evolved in the presence of microbial life and so it is unsurprising that microorganisms are functionally integrated with many aspects of animal biology. Research is revealing the numerous ways that the gut microbiome interacts with the host’s central nervous system, influencing brain development, neurochemistry, emotion and social behaviour. This microbiome–gut–brain axis is bidirectional since the behaviour and emotional state of the host can in turn alter microbiome composition and function. This thesis investigates these two-way interactions between the gut microbiome and host behaviour at the molecular, organism, population and evolutionary levels.
I demonstrate using animal models that the gut microbiome alters the expression of neuropeptide signalling pathways implicated in social and emotional behaviour, particularly in the frontal cortex. This is the first investigation into the effect of the microbiome on the brain’s opioid system. In a large human cohort I find that sociability, neuroticism, anxiety and stress are related to differences in microbiome composition and diversity, revealing a microbial dimension to human personality. I also show in a non-captive macaque population that sociability is related to differential abundances of certain bacterial taxa. From an evolutionary perspective, I find evidence that a change in gut microbiome composition may have facilitated evolution of a larger brain and complex social behaviour. Finally, I apply evolutionary theory to the microbiome–gut–brain axis and argue against the emerging hypothesis that gut microorganisms manipulate host behaviour.
This multilevel approach provides a holistic view of the microbiome–gut–brain axis, from neurogenetics, to personality, social behaviour and evolution of the social brain. Based on the novel insights from this research, I conclude that the gut microbiome is fundamental to our understanding of the mammalian brain, behaviour and evolution in ways not currently appreciated, but with implications for human psychology and well-being.

Keywords: Bifidobacterium
Mus musculus
Lactobacillus
Neuropeptides
Probiotics
Microbiome
Gut microbiome
Prebiotics
Homo sapiens
Behaviour
Microbiome-gut-brain axis
Macaca mulatta
Advisor: Burnet, P
Dunbar, R
Engineering human neural networks: controlling cell patterning and connectivity

Restorative treatments for diseases affecting the central nervous system (CNS) are difficult to develop, due to the complexity of CNS tissues and transferability issues with results from costly animal models. There is an urgent need to produce reliable, complex culture models to develop effective treatments. Such models require controlled interfaces and relevant dense neural cultures. In this thesis, techniques are developed to prepare and investigate scaffolds enabling complex structured neural model fabrication.
To facilitate development of an interface layer, neural culture on polycarbonate track-etched membranes demonstrated that the growth of neural processes through pores required confluent cultures. To direct low density cultures, funnel-shaped pores were machined into glass coverslips, and neurite interaction with angled pore edges was analysed. Live-imaging results showed that neurites more often crossed shallower edges, and retreated from steeper edges.
Concerning development of dense cultures, neural culture in non-granular hyaluronic acid (HA) hydrogels showed cell clustering and reduced neurite extension. A protocol adding secondary structure to the scaffold by granulating HA hydrogel was optimized, and cell viability and connectivity within the hydrogel were analysed. Cell viability in the granular hydrogel was comparable to the control, and there was improvement of network connectivity in granular hydrogels over non-granular counterparts.
Potential application to improve nerve graft technology motivated the design of an extrusion device that generates tertiary structure by interspersing cell-seeded and unseeded granular HA hydrogel, facilitating control of cell distribution and alignment within the scaffold. Tertiary extruded and non-extruded hydrogels were analysed, and distribution was maintained within the tertiary extruded hydrogel scaffold, without detriment to the cell functionality. It is hypothesized that additional guidance cues could be added to the scaffolds to control cellular alignment.
Findings demonstrate the fabrication of structured scaffolds optimized for neural network growth, and highlight strategies that can be used in the production of in vitro neural models for complex CNS study.

Advisor: Ye, H
Beyond implementation: mainstreaming residential solar energy in Trinidad

Small, tropical islands are energy insecure because they depend on precarious fossil fuel markets. The islands of Trinidad, Barbados and Oahu were looked at. Trinidad is the central case study and has low solar technology deployment. Barbados and Oahu have widespread residential solar energy adoption and are used as comparators. The comparisons are used to answer the question: “How could the resident population’s energy culture(s) and Government’s residential solar energy policies interact to mainstream distributed residential solar energy technologies in Trinidad?”
The Multi-Level Perspective (MLP) is used to approach energy transitions (ETs) as the product of a landscape, a regime, and niche’s interactions. Mainstreaming as a concept is not explicitly used in the MLP but refers to the process by which niche-innovations enter the regime. However, the MLP’s definition of culture was a gap in its approach to ETs. The Energy Cultures Framework is used to define ‘culture’ in the regime as ‘energy cultures’ which have norms, practices, material culture and external influences. The study investigates the role(s) of culture in ETs through the mainstreaming of distributed residential solar energy technologies in Trinidad. It focuses on the interactions between ‘culture’ and ‘policy’.
Trinidad’s historical energy policy literature was reviewed. This was followed by conducting 33 structured interviews with residents in Barbados and Trinidad, and 22 semi-structured interviews with energy officials in Oahu and Trinidad. Inductive and deductive thematic content analyses were respectively used to analyze the interviews.
Culture can create policy niches, and be considered to determine the types, goals and designs of policies that should be used to mainstream residential solar energy in Trinidad. More broadly culture transcends the three planes of the MLP and has proactive and reactive roles - which are expressed through niche-creation; technological selectivity; adaptive capacity; resisting change; and reacting to change. Mainstreaming is a useful concept in the MLP because it links innovation-adoption to socio-technical change and studying culture in the MLP broadens the consideration extended towards behaviour in socio-technical interactions.

Keywords: Small islands
Solar energy
Policy
Energy transitions
Mainstreaming
Culture
Advisor: Eyre, N
Jardine, C
Modulation of atrial fibrillation susceptibility by gp91phox-containing NADPH oxidases

Atrial fibrillation (AF) is the most frequently encountered cardiac rhythm disorder in humans, with affected individuals facing an increased risk of stroke and mortality. Published findings implicate oxidative stress in triggering the new onset of AF and in promoting the atrial electrical and structural changes that drive disease progression. NOX2-containing NADPH oxidases are a significant source of superoxide production in atrial tissues. Previous work showed that a NOX2-mediated increase in superoxide accompanies AF in patients and animal models of tachypacing-induced AF, and further reported a strong independent association between atrial NOX2 activity and post-operative AF in patients undergoing cardiac surgery. However, a direct causal role for NOX2 in AF has not been investigated. This thesis aimed to test the hypothesis that superoxide released specifically from NOX2 directly contributes to the development of AF.
To investigate the role of NOX2 in AF, mice with cardiac-specific overexpression of the human NOX2 gene (NOX2-Tg) were characterized. Atrial homogenates from these mice were found to show approximately 3-fold higher expression of NOX2 protein compared with wild-type controls, which was associated with a significant increase in NADPH-stimulated superoxide production. AF susceptibility assessed in vivo by transesophageal atrial burst stimulation was significantly higher in NOX2-Tg mice compared with wild-type, in the absence of significant alterations in cardiac function. However, dietary administration of atorvastatin (30 mg/kg daily for two weeks) did not eliminate AF susceptibility in NOX2-Tg mice, despite preventing the increase in NADPH-stimulated superoxide production in the left and right atria of these animals. Instead, atorvastatin significantly reduced the duration of pacing-induced AF, an effect which was found to be independent of genotype, and thus independent of NOX2 inhibition.
Mechanistic studies do not support a role for NOX2 in promoting electrical or structural remodelling, as high-resolution optical mapping of di-4-ANEPPS-stained atrial tissue preparations revealed no significant differences in action potential duration or conduction velocity between wild-type and NOX2-Tg mice. Instead, NOX2 overexpression was associated with impaired atrial Ca2+ handling. In left atrial myocytes of NOX2-Tg mice, the RyR2 Ca2+ leak-SR load ratio was lower when compared with wild-type, despite an increase in SR Ca2+ load. In the right atria, the leak-load ratio was similar between NOX2-Tg and wild-type myocytes, but the proportion of myocytes with ‘leaky’ RyR2 channels was greater among NOX2-Tg mice. RyR2 phosphorylation at Ser-2814 and Ser-2808 was not significantly different between WT and NOX2-Tg atrial homogenates, indicating that the changes in diastolic leak are not caused by differences in CaMKII or PKA activity.

Advisor: Casadei, B
Simon, J
N.Reilly, S
Magnetic resonance imaging of the liver. T1 dynamics: confounders and modelling

Non-alcoholic fatty liver disease (NAFLD) is becoming increasingly prevalent in the world population. The current gold standard for diagnosing NAFLD, however, is still the liver needle biopsy, the evaluation of which can be subjective, lacks good reproducibility, and suffers from sampling bias. Multiparametric MRI exams comprising measurements of proton density fat fraction, hepatic iron concentration and liver T1 values, with iron- corrected T1 measurements correlating well with liver fibrosis and inflammation, have been suggested as a good non-invasive candidate to diagnose NAFLD. However, T1 values and T1 measurement methods are affected by more than just iron. The work presented in this thesis focussed on characterising the complex dependence of T1 values on hepatic lipid concentration when using the MOLLI methods. Dependent on field strength, magnetic field inhomogeneities, and sequence parameters (such as echo time and repetition time), the deleterious effects of fat can result in an artificial increase or decrease of measured liver T1s. An algorithm capable of reversing the effects of fat and frequency offsets was developed and tested in phantoms and in prospectively recruited participants by comparing the outcome of the algorithm to liver water T1 values measured using MR spectroscopy.
Finally, two other influencing factors of liver T1 were also studied: liver glycogen concentration and body hydration status, both of which are subject to significant diurnal variation and their T1 effect has been shown earlier. A small study involving healthy vol- unteers undergoing metabolic interventions was conducted to determine the dependence of liver T1 values on liver glycogen concentration and hydration status.

Keywords: Quantitative liver MRI
Multiparametric MRI
Magnetic resonance imaging
Non-alcoholic fatty liver disease
Advisor: Robson, M
Tunnicliffe, E
Which God will save us? Jewish receptions of Martin Heidegger's philosophy

To date, scholars addressing the theme of Martin Heidegger and religion have most often examined his roots in, and impact on, Christianity. With respect to Heidegger and Judaism, critical literature has almost exclusively taken a common perspective: it discusses Heidegger’s view of Jews and the question of his antisemitism and Nazism. The present doctorate dissertation explores Jewish receptions of Heidegger’s philosophy, claiming that from immediately after the publication of Sein und Zeit and throughout the twentieth century, a central prism through which Jewish thinkers read his work was a religious one, and that they engaged with it as a provocation and challenge to Judaism, however constructed. The thesis demonstrates that Heidegger is a key reference point in the negotiation of the boundaries between Judaism, Christianity, and secularism in twentieth century Jewish thought, and that the Jewish responses to his philosophy channel a disillusionment from the political-theological premises of the modern project.

Keywords: Heidegger
Buber
Jewish Thought
Emmanuel Levinas
Leo Strauss
Advisor: Ward, G
Violence in severe mental illness: risk factors, risk assessment, and prevention

Individuals with severe mental illness are at increased risk of violence compared with the general population. Risk factors for violence need clarification as a basis for risk assessment, and to inform evidence-based risk management. The aim of this thesis is to examine the risk factors for violence in schizophrenia-spectrum disorders, create a simple, scalable risk assessment tool to predict violence in forensic psychiatric populations, and review the evidence for violence prevention interventions in psychiatry.
The first study reports risk factors for violence in a Swedish total population cohort of patients with schizophrenia-spectrum disorders (n=24,297), using register data. Substance use disorders, previous criminality, and self-harm were strong predictors of violence in patients, but also in unaffected sibling and general population controls.
The second study used pre-specified criminal, sociodemographic, and clinical risk factors to derive a clinical prediction rule for violent crime within 12 and 24 months of discharge from forensic psychiatric hospitals in Sweden (n=2,248). The model was used to develop a 12-item online tool (FoVOx) with good measures of calibration and discrimination (area under the curve = 0.77 at 12 and 24 months).
The third study reports an umbrella review of violence prevention interventions in psychiatry, through searches in ten bibliographic databases, and assesses the strength of evidence for each review using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. Out of five included reviews, only one received a GRADE rating of ‘moderate’, and reported that therapeutic community interventions may reduce reincarceration in drug-using offenders with mental illness.
Given the lack of intervention research in violence prevention in psychiatry, and considering the shared risk factors between populations, interventions from non-psychiatric populations may need to be relied upon. Research recommendations include the validation of FoVOx, and routine inclusion of violence outcomes in primary research.

Advisor: Fazel, S
A compact, high-flux source of cold atoms

The ongoing drive to transfer quantum technologies from research laboratories to practical, portable devices requires the development of multiple key enabling technologies. The field of cold atoms, which includes high-precision metrology and quantum simulation, has various real-world applications including time-keeping and navigation. A crucial component in these systems is a cold-atom source that generates a flux of low-velocity atoms suitable for subsequent capture. A large flux enables fast repetition rates, high duty cycles, long measurement times, and resistance to long-term performance degradation with a good signal-to-noise ratio, all of which are essential to produce cold-atom devices and technologies that are capable of out-performing the classical alternatives.
This thesis presents the design, fabrication and characterisation of a novel cold-atom source using a compact pyramidal magneto-optical trap (MOT) with a unique adjustable-aperture mechanism. This allowed an investigation of the dependence of the flux characteristics on the aperture size, a parameter space that has not previously been explored. The measurements showed a strong dependence of the flux on the aperture size, with a negligible flux below 0.4mm, then an approximately linear increase up to 1.0mm, at which point the relationship showed possible signs of saturation. Using 87Rb, a flux of 1.18×1010 atoms/s was produced using a 1.27mm aperture, for which the mean velocity of the atoms was 21.6(3) m/s with a FWHM of 11.2(2) m/s, and the FWHM divergence of the beam was 86(2) mrad. This is the highest recorded flux from a pyramid or 2D+-MOT source, and amongst the highest reported fluxes from any MOT sources, and avenues for improvement still remain. This work fulfils the aim of demonstrating a compact and robust cold-atom source generating a high flux of laser-cooled atoms for real-world quantum technology applications.

Keywords: Atom source
Quantum technology
Magneto-optical trap
Cold-atom source
Pyramid mirror
Adjustable aperture
Pyramid MOT
Ultracold atoms
High flux
Laser cooling
MOT
Advisor: Foot, C