VictorJuiz/thesis huggingface dataset:
Methods for determining lung function from tracer gas concentrations

The ability to routinely determine Functional Residual Capacity (FRC) or the ventilation-volume homogeneity of ventilated patients has been a long held goal. Such measures have the potential to greatly improve the treatment of patients by preventing ventilator related lung injuries. Many methods have been proposed, but none have seen routine clinical use. This thesis develops methods of determining such information from tracer gas concentrations, modelling the concentration of the entire expired breath in an attempt to extract more information from the data.
A method of using such models to produce a distribution of alveolar volumes, which broadens with an increase in the inhomogeneity of simulated data, was developed. When compared to the Homogeneity Index [Whiteley et al., Respir. Physiol., 124(1):65-83.], the method determines the homogeneity more robustly, particularly when noise is present in the flow signal. In real data from a water-displacement bench lung it also produced tentatively better results. However it did not perform as expected for 25% of the data sets.
Investigations into determining FRC, highlighted the need to include mixing within the dead space, which is a move away from traditional dead space models. In human data a dead space with two mixing compartments provided the best FRC results, reducing the mean limits of agreement with plethysmography by 32% when compared to the other practical methods investigated. Compared to data from the literature, this method was no worse than Helium Dilution (the bias and limits of agreement were within the 95% confidence interval) and the limits of agreement were significantly better than for the LUFU device. Thus, if the results are replicated in clinical practice, the method is likely to be robust enough to positively influence patient care. Attempts to correct for time offsets between the flow and concentrations signals did not improve results for humans, despite showing some improvements for a water-displacement bench lung.

Keywords: Approximate Bayesian computation (ABC)
Lung function testing
Mathematical modelling
Parameter estimation
Model selection
Mechanical ventilation
Ventilator associated lung injury
Intensive care unit
Advisor: Payne, S
Risk-based flood protection decisions in the context of climatic variability and change

Flood events have caused detrimental impacts to humans' lives and anthropogenic climate change is anticipated to exacerbate the impact. It has been recognized that a long-term planning through risk-based optimization of flood defence will lead to a cost-effective solution for managing flood risk, but the prevailing assumption of stationarity may lead to an erroneous solution. In attempt to investigate the potential impact of the uncertain underlying statistical characteristics of extreme flow series to flood protection decisions, this research explores risk-based flood protection decisions in the context of climatic variability and change. In particular, the implications of persistence series and nonstationarity were investigated through hypothetical and real case studies. Monte Carlo simulation approach was adopted to capture the uncertainty due to the natural variability. For persistence model, AR(1) was integrated with the GEV model to simulate extreme flow series with persistence. To test the effects of nonstationary, GEV models with a linear location parameter and time as covariate were adopted. Rational decision makers' behaviours were simulated through a designed decision analysis framework. One of the main findings from the research is that the traditional stationary assumption should remain the basic assumption due to insignificant difference of the decisions’ economic performance. However, exploration of the nonstationarity assumption enabled identification of options that are robust to climate uncertainties. It is also found that optimized protection of combined measures of flood defence and property-level protection may provide a cost-effective solution for local flood protection. Overall, the simulation and case studies enlighten practitioners and decision makers with new evidence, and may guide to practical enhancement of long term flood risk management decision making.

Keywords: decision analysis
nonstationary
flood risk assessment
Advisor: Hall, J
On verification and controller synthesis for probabilistic systems at runtime

Probabilistic model checking is a technique employed for verifying the correctness of computer systems that exhibit probabilistic behaviour. A related technique is controller synthesis, which generates controllers that guarantee the correct behaviour of the system. Not all controllers can be generated offline, as the relevant information may only be available when the system is running, for example, the reliability of services may vary over time.
In this thesis, we propose a framework based on controller synthesis for stochastic games at runtime. We model systems using stochastic two-player games parameterised with data obtained from monitoring of the running system. One player represents the controllable actions of the system, while the other player represents the hostile uncontrollable environment. The goal is to synthesize, for a given property specification, a controller for the first player that wins against all possible actions of the environment player. Initially, controller synthesis is invoked for the parameterised model and the resulting controller is applied to the running system. The process is repeated at runtime when changes in the monitored parameters are detected, whereby a new controller is generated and applied. To ensure the practicality of the framework, we focus on its three important aspects: performance, robustness, and scalability.
We propose an incremental model construction technique to improve performance of runtime synthesis. In many cases, changes in monitored parameters are small and models built for consecutive parameter values are similar. We exploit this and incrementally build a model for the updated parameters reusing the previous model, effectively saving time.
To address robustness, we develop a technique called permissive controller synthesis. Permissive controllers generalise the classical controllers by allowing the system to choose from a set of actions instead of just one. By using a permissive controller, a computer system can quickly adapt to a situation where an action becomes temporarily unavailable while still satisfying the property of interest.
We tackle the scalability of controller synthesis with a learning-based approach. We develop a technique based on real-time dynamic programming which, by generating random trajectories through a model, synthesises an approximately optimal controller. We guide the generation using heuristics and can guarantee that, even in the cases where we only explore a small part of the model, we still obtain a correct controller.
We develop a full implementation of these techniques and evaluate it on a large set of case studies from the PRISM benchmark suite, demonstrating significant performance gains in most cases. We also illustrate the working of the framework on a new case study of an open-source stock monitoring application.

Advisor: Kwiatkowska, M
Parker, D
Three-dimensional dislocation dynamics modelling of particle-reinforced ferrous alloys for nuclear applications

An existing point defect bulk diffusion model of dislocation climb is developed to incorporate both vacancies and interstitials, and supersaturations of these defects. Calculations are carried out for body-centred cubic (bcc) iron using this model, which show that the interstitial nature of experimentally observed irradiation-induced damage loops can be explained by the preferential osmotic absorption of supersaturated interstitials over vacancies by damage loops.
The model is implemented into a 3D dislocation dynamics code, together with a dual glide and climb time step method, and spherical obstacles which are impenetrable to dislocations, all of which required original code development. Simulations of dislocation-inclusion unpinning via climb in particle-reinforced bcc iron are conducted, and the creep strain rate is estimated from the unpinning time data. The thermal creep strain rates are seen to be strongly temperature-dependent, as expected. Varying the applied load and dispersion properties is seen to have a relatively small effect, and remarkably the creep rates exhibit no dependence on the particle size and number density for a given volume fraction of obstacles. The thermal creep strain rates predicted are consistent with experimental observation.
The irradiation creep strain rates are seen to vary much less strongly with temperature, also as expected. These results suggest that in particle-reinforced alloys under advanced nuclear reactor operating conditions, it is possible the irradiation creep rate will be orders of magnitude larger than the thermal creep rate at this temperature, depending on the value of the steady-state point defect supersaturations available to drive dislocation climb. In this case, the use of such alloys for advanced nuclear applications will be somewhat limited.

Keywords: Irradiation damage
Oxide Dispersion Strengthening (ODS)
Dislocation dynamics
Advisor: Roberts, S
Fitzgerald, S
Tarleton, E
A perinatal monitoring system for low-resource settings

The reduction of maternal and child morality has been central to international development efforts over the past twenty years, spurred on by global initiatives such as the Millennium Development Goals. Whereas a significant decrease in mortality rates has been achieved in mothers and the under-five, the fetal and early neonatal period has received less attention resulting in slower progress. Resource-poor settings suffer from the highest stillbirth, maternal and early neonatal death rates, with 99% occurring in low- and middle income countries.
Causes of fetal and maternal compromise can be manifold, both infrastructural and pathophysiological. Common problems remain a scarcity of skilled healthcare personnel leading to low health risk detection, referral and ultimately intervention rates. In the absence of sophisticated equipment fetal compromise may go unnoticed, such as fetal growth restriction, one of the primary causes of poor health outcome.
To work towards improved fetal and maternal risk assessment enabling timely and appropriate referral, this thesis proposes a low-cost mHealth monitoring platform for use in low-resource settings. The analysis of the fetal cardiac activity, prerequisite in hospitals in developed nations, may provide important insights on fetal stress levels and more specifically growth retardation. The fetal cardiac signal is accessible and obtained at low-cost with the help of a Doppler transducer. This thesis in healthcare innovation investigates the feasibility of introducing such technology in communities not familiar with their application, proposes a novel signal quality algorithm suitable for implementation on the phone, develops a classifier based on fetal heart rate variability to distinguish growth restricted from normal babies, and introduces the design of the mHealth platform, results of a pilot deployment in rural Guatemala and the design and implementation of a full randomised control trial.

Keywords: Low-cost fetal monitoring
Fetal risk assessment in low-resource settings
Global Health
Automated IUGR risk detection
Decision support for traditional birth attendants
mHealth
Advisor: Clifford, G
Payne, S
Recursive construction of continuum random trees and some contributions to the theory of tree-valued stochastic processes

We introduce a general recursive method to construct continuum random trees (CRTs) from i.i.d. copies of a string of beads, that is, any random interval equipped with a random discrete measure. We prove the existence of these CRTs as a new application of the fixpoint method formalised in high generality by Aldous and Bandyopadhyay. We further apply this recursive construction to "embed" Duquesne and Le Gall's stable tree into a binary compact CRT in a way that solves an open problem posed by Goldschmidt and Haas. Some of these developments are carried out in a space of ∞-marked metric spaces generalising Miermont’s notion of a k-marked metric space.
Furthermore, we introduce a family of branch merging operations on continuum trees and show that Ford CRTs are distributionally invariant. This operation is new even in the special case of the Brownian CRT, which we explore in more detail. The operations are based on spinal decompositions and a regenerativity preserving merging procedure of (α, θ)-strings of beads, that is, regenerative strings of beads arising in the limit of ordered (α, θ)-Chinese restaurant processes as introduced by Pitman and Winkel. Indeed, we iterate the branch merging operation recursively and give a new approach to the leaf embedding problem on Ford CRTs related to (α, 2−α)-tree growth processes.

Keywords: regenerative interval partition
line-breaking construction
string of beads
Brownian CRT
marked metric space
recursive distribution equation
tree-valued Markov process
Chinese restaurant process
stable tree
Poisson-Dirichlet
branch merging
continuum random tree
Ford CRT
Advisor: Winkel, M
Algorithmic verification problems in automata-theoretic settings

Problems in formal verification are often stated in terms of finite automata and extensions thereof. In this thesis we investigate several such algorithmic problems.
In the first part of the thesis we develop a theory of completeness thresholds in Bounded Model Checking. A completeness threshold for a given model M and a specification φ is a bound k such that, if no counterexample to φ of length k or less can be found in M, then M in fact satisfies φ. We settle a problem of Kroening et al. [KOS+11] in the affirmative, by showing that the linearity problem for both regular and ω-regular specifications (provided as finite automata and Buchi automata respectively) is PSPACE-complete. Moreover, we establish the following dichotomies: for regular specifications, completeness thresholds are either linear or exponential, whereas for ω-regular specifications, completeness thresholds are either linear or at least quadratic in the recurrence diameter of the model under consideration.
Given a formula in a temporal logic such as LTL or MTL, a fundamental problem underpinning automata-based model checking is the complexity of evaluating the formula on a given finite word. For LTL, the complexity of this task was recently shown to be in NC [KF09]. In the second part of the thesis we present an NC algorithm for MTL, a quantitative (or metric) extension of LTL, and give an AC1 algorithm for UTL, the unary fragment of LTL. We then establish a connection between LTL path checking and planar circuits which, among others, implies that the complexity of LTL path checking depends on the Boolean connectives allowed: adding Boolean exclusive or yields a temporal logic with P-complete path-checking problem.
In the third part of the thesis we study the decidability of the reachability problem for parametric timed automata. The problem was introduced over 20 years ago by Alur, Henzinger, and Vardi [AHV93]. It is known that for three or more parametric clocks the problem is undecidable. We translate the problem to reachability questions in certain extensions of parametric one-counter machines. By further reducing to satisfiability in Presburger arithmetic with divisibility, we obtain decidability results for several classes of parametric one-counter machines. As a corollary, we show that, in the case of a single parametric clock (with arbitrarily many nonparametric clocks) the reachability problem is NEXP-complete, improving the nonelementary decision procedure of Alur et al.. The case of two parametric clocks is open. Here, we show that the reachability is decidable in this case of automata with a single parameter.

Keywords: temporal logic
parametric timed automata
automata theory
formal verification
bounded model checking
Advisor: Ouaknine, J
Dissecting the mechanisms of pacemaking in the heart using photo-affinity probes and pharmacological intervention

The aim of the work described in this thesis was to dissect the mechanisms underlying pacemaking in the heart using both pharmacological and chemical tools. The mechanisms underlying pacemaker activity in the sino-atrial node are controversial, with some researchers giving prominence to the role of the 'funny' current, If, others emphasising a 'calcium clock', and with still others highlighting the elusive sustained inward current, Ist.
Autonomic modulators, particularly adrenaline and noradrenaline regulate all the proposed mechanisms. To investigate which adrenoceptors are responsible for driving positive chronotropic action in the heart, adrenoceptors α1, β1 and β2 were studied using selective blockers (prazosin, CGP20712A and ICI118551, respectively). The results imply that activation of the β1-adrenoceptor pathway is responsible for most positive chronotropic actions in the mouse heart.
Selective blockers of If (ZD7288, ivabradine) and sarcoplasmic reticulum (SR) [ryanodine and cylopiazonic acid (CPA)] were used to explore the contributions of If and Ca2+ release from SR to cardiac pacemaking in the absence and presence of adrenoceptor stimulation. The results showed that both If and Ca2+ release from SR significantly contribute to pacemaking both in the presence or absence of β adrenoceptor stimulation. They also show that the effects of ivabradine and ZD7288 on heart rate are substantially reduced following CPA or ryanodine administration; this may reflect a possible effect of reduced activity of Ca2+-stimulated adenylyl cyclases (AC) present in SAN cells. To investigate this phenomenon genetically modified mice lacking Ca2+-stimulated (AC) were used. Contrary to predictions, the resting heart rates and responses to If blockers, CPA blockers and isoprenaline from genetically modified mice showed only small differences relative to control mice.
With aim of identifying the sequence of the Ist protein a series of photo-affinity probes were developed to enable covalent photocapture of the Ist ion channel following exposure to UV light. Proof of concept studies involved for photo-crosslinking and pull-down experiments in pursuit of identifying the Cav1.2 channel. Subsequent to cross-linking the photo-affinity probe to its target, Western blot analysis identified a &Tilde;190 kD band, consistent with the L-type Ca2+ channel.

Advisor: Schofield, C
Kawamura, A
A multi-paradigm modelling framework for simulating biocomplexity

The following thesis presents a computational framework that can capture inherently non-linear and emergent biocomplex phenomena. The main motivation behind the investigations undertaken was the absence of a suitable platform that can simulate, both the continuous features as well as the discrete, interaction-based dynamics of a given biological system, or in short, dynamic reciprocity. In order to determine the most powerful approach to achieve this, the efficacy of two modelling paradigms, transport phenomena as well as agent-based, was evaluated and eventually combined. Computational Fluid Dynamics (CFD) was utilised to investigate optimal boundary conditions, in terms of meeting cellular glucose consumption requirements and exposure to physiologically relevant shear fields, that would support mesenchymal stem cell growth in a 3-dimensional culture maintained in a commercially available bioreactor. In addition to validating the default bioreactor configuration and operational parameter ranges as suitable towards sustaining stem cell growth, the investigation underscored the effectiveness of CFD as a design tool. However, due to the homogeneity assumption, an untenable assumption for most biological systems, CFD often encounters difficulties in simulating the interaction-reliant evolution of cellular systems. Therefore, the efficacy of the agent-based approach was evaluated by simulating a morphogenetic event: development of in vitro osteogenic nodule. The novel model replicated most aspects observed in vitro, which included: spatial arrangement of relevant players inside the nodule, interaction-based development of the osteogenic nodules, and the dependence of nodule growth on its size. The model was subsequently applied to interrogate the various competing hypotheses on this process and identify the one that best captures transformation of osteoblasts into osteocytes, a subject of great conjecture. The results from this investigation annulled one of the competing hypotheses, which purported the slow-down in the rate of matrix deposition by certain osteoblasts, and also suggested the acquisition of polarity to be a non-random event. The agent-based model, however, due to being inherently computationally expensive, cannot be recommended to model bulk phenomena. Therefore, the two approaches were integrated to create a modelling platform that was utilised to capture dynamic reciprocity in a bioreactor. As a part of this investigation, an amended definition of dynamic reciprocity and its computational analogue, dynamic assimilation, were proposed. The multi-paradigm platform was validated by conducting melanoma chemotaxis under foetal bovine serum gradient. Due to its CFD and agent-based modalities, the platform can be employed as both a design optimisation as well as hypothesis testing tool.

Keywords: bioreactors
dynamic assimilation
computational fluid dynamics
Agent-based modelling
design
biocomplexity
dynamic reciprocity
osteocytes
stem cells
osteblasts
osteogenesis,
Advisor: Ventikos, Y
Cui, Z
Social policy, protest participation and violent crime in Latin America

This thesis consists of four self-contained articles which focus on different aspects of citizens' demand for and governments' supply of social policy in Latin American democracies. The underlying questions that link the four papers are a) do social and economic grievances affect citizens' propensity to protest? and, b) do democratic governments in the region use social policy as an instrument to mitigate social discontent and violent crime? In the first two papers, I use public opinion data in order to examine the determinants of citizens' participation in protest with a special focus on dissatisfaction with the quality of public services, demands for inequality-reduction policies and economic deprivation. The results show that among other factors, protest participation is motivated by citizens' discontent over the quality of basic social services, support for redistributive policies, and relative economic deprivation. The third and fourth papers analyze the "supply side" of social spending in the region focusing on collective protest and violent crime, respectively. The third article argues that under democracy, organized labor is in a better position relative to other groups in society to obtain social policy concessions as a consequence of their collective action efforts. The results show that whereas social security spending increases as a consequence of labor militancy, cutbacks in human capital spending are less likely as peaceful large-scale demonstrations increase. The fourth paper argues that political leaders use education spending as an instrument to mitigate violent crime. It also argues that the effect of violent crime on education spending is larger when leftist governments are in power. The empirical analysis provides support for these arguments.

Keywords: Latin America
violence
social protest
Advisor: Rueda, D
Seeleib-Kaiser, M