VictorJuiz/thesis huggingface dataset:
Haemodynamic status and management of shock in children with severe febrile illness

Most in-hospital deaths secondary to infections in under-five deaths within sub-Saharan Africa (SSA) occur in the initial 24 hours of admission and shock has been identified as a major risk factor for the early deaths. However, controversies exist on the appropriate clinical diagnosis of shock, choice of ideal fluid for resuscitation (crystalloid or colloid), and safety of fluid resuscitation in severe malnutrition or severe malaria. This thesis investigates these aspects and also reviews the evidence base of current paediatric fluid resuscitation guidelines for children (aged >60 days and ≤12 years) with severe febrile illnesses.
Capillary refill time >2 seconds, weak pulse volume, or bradycardia, in the presence of abnormal temperature and severe disease are predictive of impaired perfusion (defined by lactic acidosis) and death. Tachycardia and temperature gradient are neither associated with increased risk of death nor predictive of hypoperfusion. Existing international definitions of shock have low sensitivities (FEAST=44%, WHO=2%, and ACCM=59%) and high specificities (FEAST=82%, WHO=100%, and ACCM=66%) for diagnosis of impaired perfusion. Clinical criteria derived (called derived shock) had a sensitivity of 30% and specificity of 93%.
Shock in children with severe febrile illnesses in Kilifi has a complex presentation but mainly presents with hyperdynamic circulation (high cardiac index) and vasodilatation. Cases with low cardiac index (myocardial dysfunction) are relatively rare but increase the risk of mortality when present.
Synthetic colloids (gelofusine, hydroxyethyl starch 130/0.4 (HES), and dextran 70) are safe for use in fluid resuscitation in children with severe malaria. However, HES is the most promising compared to other synthetic colloids concerns still remain about its renal safety. However, further evaluation of synthetic colloids for treatment of shock is not warranted due to the findings of FEAST trial.
A Pilot trial shows that bolus isotonic fluids are safe, have better efficacy, and produce faster resolution of shock compared to low-sodium solutions at volumes and rates recommended by WHO in children with severe malnutrition.
Evidence available from all ten the trials in children with sepsis show that fluid resuscitation using crystalloids and colloids result in similar survival. However, fluid bolus resuscitation results in increased mortality compared to no bolus (control) in children in SSA. This finding excludes children with gastroenteritis, trauma, burns, and malnutrition. Colloids are better than crystalloids for severe dengue shock but both have similar efficacy in moderate dengue shock.

Keywords: volume expansion
resuscitation
management
malaria
malnutrition
fluids
colloids
shock
children
Advisor: Maitland, K
Angus, B
A structural and functional analysis of CPF1, a bHLHZIP protein of Saccharomyces cerevisiae

CPF1 (centromere promoter factor 1) of Saccharomyces cerevisiae is a multifunctional protein. This multifunctionality may be associated with the different forms of the protein. To date, no clear function has been attributed to this protein. The general roles currently attributed to CPF1 are: maintenance of proper chromosome segregation or centromere function; methionine prototrophy and chromatin modulation. A series of recent papers have suggested the possibility of CPF1 being involved in protein-protein interactions. This thesis shows that CPF1 has an additional protein-protein interaction domain which is a coiled-coil. A truncation of CPF1 coding for only the C-terminal dimerization motif was cloned into a 17 expression vector and the protein, Dd, was produced in and purified from E. coli. Characterisation of the conformation of the C-terminal dimerization domain of CPF1 show the presence of a leucine zipper in Dd and that Dd forms a dimer under physiological conditions. Sequence alignment analysis of CPF1 and other bHLHZIP proteins identified a conserved serine residue in the basic domain of CPF1 and a conserved asparagine residue in the leucine zipper. Point mutations were introduced separately mutating these residues into either alanine or glutamate. The mutant alleles were cloned into yeast expression vectors. The cloned alleles were used to transform YAG93, a cpf1 deletion strain. Characterisation of the transformants obtained indicate the possibility of CPF1 being involved in the spindle assembly checkpoint control, possibly as a tethering protein. Finally, attempts were made to identify interacting partners of CPF1 and a purification scheme was designed to purify a putative CPF1 complex. Initially, a GST-CPF1 chimera was used to screen radioactively labelled crude yeast extracts for interacting partners of CPF1. This strategy identified five or six potential proteins which might form a multiprotein complex with CPFl. Attempts were then made to purify this putative complex from S. cerevisiae. The partially purified extracts were tested for CDEI activity, indicative of the presence of CPF1 in the samples and. tjhen analysed for protein content. The samples were also tested in a Holiday junction binding assay and in a histone acetyltransferase activity assay. In conclusion, CPF1 is a bHLHZIP protein that has a role in nutrient signalling and checkpoint control, possibly by acting as an intermediary protein that recruits essential factors to gene promoters or the centromere by protein-protein interactions.
The regular histories formulation of quantum theory

A measurement-independent formulation of quantum mechanics called ‘regular histories’ (RH) is presented, able to reproduce the predictions of the standard formalism without the need to for a quantum-classical divide or the presence of an observer. It applies to closed systems and features no wave-function collapse.
Weights are assigned only to histories satisfying a criterion called ‘regularity’. As the set of regular histories is not closed under the Boolean operations this requires a new con- cept of weight, called ‘likelihood’. Remarkably, this single change is enough to overcome many of the well-known obstacles to a sensible interpretation of quantum mechanics. For example, Bell’s theorem, which makes essential use of probabilities, places no constraints on the locality properties of a theory based on likelihoods. Indeed, RH is both counter- factually definite and free from action-at-a-distance.
Moreover, in RH the meaningful histories are exactly those that can be witnessed at least in principle. Since it is especially difficult to make sense of the concept of probability for histories whose occurrence is intrinsically indeterminable, this makes likelihoods easier to justify than probabilities.
Interaction with the environment causes the kinds of histories relevant at the macroscopic scale of human experience to be witnessable and indeed to generate Boolean algebras of witnessable histories, on which likelihoods reduce to ordinary probabilities. Further- more, a formal notion of inference defined on regular histories satisfies, when restricted to such Boolean algebras, the classical axioms of implication, explaining our perception of a largely classical world.
Even in the context of general quantum histories the rules of reasoning in RH are remark- ably intuitive. Classical logic must only be amended to reflect the fundamental premise that one cannot meaningfully talk about the occurrence of unwitnessable histories.
Crucially, different histories with the same ‘physical content’ can be interpreted in the same way and independently of the family in which they are expressed. RH thereby rectifies a critical flaw of its inspiration, the consistent histories (CH) approach, which requires either an as yet unknown set selection rule or a paradigm shift towards an un- conventional picture of reality whose elements are histories-with-respect-to-a-framework.
It can be argued that RH compares favourably with other proposed interpretations of quantum mechanics in that it resolves the measurement problem while retaining an essentially classical worldview without parallel universes, a framework-dependent reality or action-at-a-distance.

Keywords: interpretation
quantum mechanics
quantum theory
consistent histories
regular histories
histories
Advisor: Abramsky, S
Periodically driven atomic systems

This thesis is concerned with a variety of topics grouped together under the general theme of periodically driven atomic systems. Periodic driving is ubiquitous in most techniques used in atomic physics, be it laser cooling, ion trapping or AC magnetic fields. An in-depth understanding of the behaviour of such systems can be provided through Floquet theory which will develop as a central theme in the following chapters.
The thesis is divided in two parts: neutral atoms, and ions and biomolecules. In the first part I discuss a new 41K-87Rb mixture experiment, built during the first year of my DPhil. This species combination has some very broad and low-loss interspecies Feshbach resonances that are instrumental for carrying out the experiments discussed in the first chapter. Unfortunately, the mixture experiment had to be put aside and our attention was shifted to Time-Averaged Adiabatic Potentials (TAAPs) and how these can be extended using multiple Radio-Frequency (RF) fields. This technique opens up the way for precise interferometric measurements. Lastly, the peculiar behaviour of Modulation Transfer Spectroscopy (MTS) of 39K is investigated and a linearising transformation for four-wave mixing processes is presented.
In the second part we turn our attention to charged ions and biomolecules and the techniques of ion trapping. We propose a novel technique for co-trapping charged particles with vastly different mass-to-charge ratios and thoroughly explore its consequences. The behaviour of the trap and the stability of equations with periodic coefficients in general is studied using Floquet theory. The normal modes and symmetries of the system also need to be considered in relation to the effectiveness of the sympathetic cooling of the ions. Small systems were simulated using a Molecular Dynamics (MD) approach in order to capture the effect of micromotion and other heating processes.

Keywords: ultracold atoms
Floquet theory
spectroscopy
BEC
ion traps
Advisor: Foot, C
Search for new physics in the dijet invariant mass spectrum at 8 TeV

A search for resonance signals from new physics models was performed using the ATLAS dijet invariant mass spectrum at a center-of-mass energy of 8 TeV. The full dataset from the 2012 data-taking period was used, corresponding to an integrated luminosity of 20.3 fb−1. The analysis covered a mass range from 250 GeV to 4.5 TeV and found no evidence of an excess anywhere in the spectrum. Upper mass limits were set at 95% CL on both model- specific benchmark new physics signals and on two different generic resonance forms: a Gaussian shape and a Breit-Wigner shape which accounted for pdf and detector effects. The analysis excluded excited quarks below 4.06, heavy W' bosons below 2.45, colour-octet scalars below 2.70, leptophobic chiral excited bosons W* below 1.75, and quantum black holes below 5.66 and 5.62 for the Qbh and BlackMax generators respectively.

Keywords: jets
exotic searches
high energy physics
Advisor: Tseng, J
Organic-inorganic hybrid photovoltaics based on organometal halide perovskites

This thesis details the development of a novel photovoltaic device based on organometal halide perovskites. The initial focus of this thesis begins with the study of lighttrapping strategies in solid-state dye-sensitised solar cells (detailed in chapter 3). While I report enhancement in device performance through the application of near and far-ﬁeld light-trapping techniques, I ﬁnd that improvements remain step-wise due to fundamental limitations currently employed in dye-sensitised solar cell technology— notably, the available light-sensitising materials. I found a promising yet under researched family of materials in the methyl ammonium tri-halide plumbate perovskite (detailed in chapter 4). The perovskite light-sensitiser was applied to the traditional mesoscopic sensitised solar cell device architecture as a replacement to conventional dye yielding world-record breaking photo-conversion e!ciencies for solid-state sensitised solar cells as high as 8.5%. The system was further developed leading to the conception of a novel device architecture, termed the mesoporous superstructured solar cell (MSSC), this new architecture replaces the conventional mesoporous titanium dioxide semiconductor with a porous insulating oxide in aluminium oxide, resulting in very low fundamental losses evidenced through high photo-generated open-circuit voltages of over 1.1 V. This development has delivered striking photo-conversion ef- ﬁciencies of 10.9% (detailed in chapter 6).

Keywords: solar cell
perovskites
organic-inorganic hybrids
photovoltaics
Advisor: Snaith, H
The 'Full Liberty of Public Writers': special treatment of institutional journalistic speech in English law 

This paper is an investigation into one aspect of the constitutionality of journalistic freedom in the law of England and Wales. It argues that there are instances where the law provides special treatment for the expression of institutional journalists, and that this is legitimate. The paper has two distinct parts, the doctrinal and the theoretical. Chapter one is doctrinal, and establishes that the law does provide special treatment to institutional journalistic speech. It classifies such treatment, demonstrating that these privileges come in different forms, and create different layers of rights. These forms can be distinguished according to whether the privileges are afforded to institutional journalists or functional journalism, or merely to general speech. The theoretical part of this paper forms chapters two and three. Chapter two assumes that the provision of special treatment to institutional journalists is justified where institutional journalistic speech particularly promotes free speech values. It argues that institutional journalistic speech does indeed perform such a function, by virtue of particular characteristics it possesses, namely reach and reputation, which are employed in processes such as reporting, investigating and interrogating. Chapter three considers the counter-arguments to this position. First it considers some arguments that challenge the thesis assumed in chapter two, and then it considers more specific criticisms of the provision of special treatment to institutional journalistic speech. It concludes that, while these limit the validity of the law’s affording special treatment to institutional journalistic speech, they do not extinguish it.

Keywords: freedom of speech
journalism
press freedom
freedom of the press
Advisor: Young, A
The numerical modelling of steep waves interacting with structures

The interaction of steep waves with structures is a complex problem which is still not fully understood, and is of great importance for the design of offshore structures. A particular problem of interest is the phenomenon of ringing which is highly nonlinear.
In this thesis a number of inviscid free surface flow problems are simulated using a finite element model. The free surface boundary condition is fully nonlinear, meaning nonlinear effects up to very high order can be simulated, depending on mesh resolution. The model uses a fully automatic unstructured mesh generator; this allows the mesh to change its shape and structure as the free surface deforms.
Two unstructured mesh generators have been developed, one based on the advancing front method, the other on the Voronoi technique. Variations of each method are examined. Both methods give good quality meshes. The advancing front technique is found to be faster, but the Voronoi method is more robust and reliable.
In addition to the standard finite element method, a sigma transformed version of the finite element formulation has been developed as an alternative. Both techniques have been used for the numerical simulations. The sigma transformation involves stretching of the mesh between the bed and free surface, and so has the advantage that remeshing is avoided. The standard finite element method is straightforward to apply to problems involving submerged arbitrary shaped bodies.
Simulations have been performed of a number of test cases, such as a standing wave of large amplitude, a base excited tank and steep travelling waves. Convergence tests were carried out and results found to be in close agreement with analytical and alternative numerical solutions of Wu and Eatock Taylor (1994), Wu et al. (1998) and Chern et al. (1999).
The force on a submerged horizontal cylinder due a travelling wave has been calculated. First and second order components have been obtained by Fourier analysis. The results have been compared with the theoretical predictions of Ogilvie (1963), Vada (1987) and Wu and Eatock Taylor (1990) and the experimental results of Chaplin (1984).

Advisor: Borthwick, A
Investigation of the contribution of cutaneous HPV E6 proteins towards the development of non melanoma skin cancer

Sunlight is the main aetiological agent in the development of non melanoma skin cancer (NMSC), the most commonly diagnosed cancer in the fair skinned population. Mounting epidemiological and molecular data suggest that infection with cutaneous Human papillomavirus (HPV) may act as a co-factor in the early stages of NMSC development. The viral E6 protein can inhibit the apoptotic response to UV induced damage, partly through proteasomal degradation of the pro-apoptotic protein BAK. Upon UV damage, BAK undergoes a series of activating modifications that are linked to changes in phosphorylation status. BAK activation commits a cell to apoptosis through mitochondrial permeabilisation.
The aim here was to elucidate the underlying mechanism of HPV5 E6-mediated BAK degradation. Mutation of lysine 113 in BAK and siRNA knockdown of a novel HPV5 E6 associated ubiquitin ligase, HERC1, prevented HPV5 E6 mediated-BAK degradation. A proximity ligation in situ assay showed an interaction between HERC1 and BAK in cells, which was dependent on the presence of the E6 protein and UV irradiation. Probing the BAK conformation and phosphorylation status suggests E6 targets a dephosphorylated BAK monomer before mitochondrial permeabilisation occurs, leading to the proposal of a mechanism for the interaction of BAK with HERC1 which depends on the activation status of BAK and a putative BH3 domain identified in HERC1.
Additional work identifies β1-integrin as an interacting protein of a conserved YHDW amino acid motif at the C-terminus of certain β1 HPV E6 proteins. Only expression of E6 proteins with the YHDW motif (HPV5 and 8) in keratinocytes disrupted β1 integrin membrane localisation, altered expression of β1 integrin downstream effectors, such as focal adhesion kinase, and increased cell migration. Mutation of W157A in the HPV5 E6 YHDW motif reduced these effects.
Together, this work furthers the understanding of mechanisms by which infection with HPV may promote the early stages of NMSC development.

Keywords: BAK
Integrin Beta 1
Apoptosis
HPV
Advisor: Storey, A
Reflection and scattering from CO₂-laser-produced plasmas

An experimental study of the interaction between 10.59 μm C02-laser radiation and the plasma produced by that radiation on plane, massive targets in a vacuum, is described. The laser used was a TEA double discharge device, giving an in vacuo irradiance in the regime of 1012 W/cm2 with 50 ns FWHM gain switched pulses. The laser oscillator cavity was operated in both stable and unstable configurations.
Particular emphasis was placed on the full diagnosis of the scattered light and experiments were, therefore, designed to investigate the spatial, temporal and spectral characteristics of this unabsorbed fraction.
The irradiation conditions under which the experiments were performed were investigated by analysis of the far field energy distribution.
High absorption of the incident radiation was inferred from the low reflectivity level, the fraction of the incident radiation scattered out- side the solid angle of the focusing lens being accounted for, using a novel collecting mirror, or by the use of calibrated burn paper. Thus a total reflection was measured for the first time. A simple model was developed to enable the classical absorption contribution to the total absorption to be estimated, and results indicated that inverse bremsstrahlung absorption would be an important process for the conditions pertinent to the interac- tion. The contribution of anomalous absorption and scattering processes was estimated. Predicted cold electron temperatures and density scale lengths from the model, agreed well with those determined experimentally without the need to invoke flux inhibition.
The spectral composition of the backscattered radiation in the region of the fundamental was investigated, and measured spectra were successfully interpreted by considering the stimulated Brillouin scattering process, and the Doppler effect of the expanding plasma corona. In particular, the depen- dence of the parametric growth rate on electron density was investigated by numerical solution of the ion acoustic wave dispersion relation.
The angular distribution of the backscattered radiation was determined using annular apertures in the backscattered beam and the distribution found to be non-isotropic. Interpretation was based upon the resonance absorption process in a non-planar plasma geometry and invoked the retro reflecting nature of the stimulated Brillouin scatter mechanism.
To investigate the effect of wave refraction in the underdense plasma (exhibiting a continuous density profile), a compact and readily used ray-tracing routine was developed and applied to plasmas with planar, rippled and simple concave or convex iso-density contours.

Advisor: Spalding, I