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Lifestyle as Therapy for Liver Disease
Get PDFPh. D. Thesis.Liver disease is the most rapidly growing chronic disease in the UK. ‘Liver disease’ comprises
a vast range of aetiologies. Non-alcoholic fatty liver disease (NAFLD) is an individual aetiology
that encompasses a range of disease severities, from simple fatty liver through to advanced
fibrosis and cirrhosis of the liver. It is estimated that up to 33% of adults within the Western
population have NAFLD, with up to 11% of those developing advanced liver disease. It is
predicted that by 2030, NAFLD will be the leading indication for liver transplantation. The aim
of this thesis was to assess the potential role of lifestyle intervention as a therapy for
advanced liver disease including patients awaiting liver transplantation.
NAFLD is strongly associated with excessive caloric consumption, sedentary behaviour, and
being overweight/obese. In the absence of approved pharmacological treatments, weight loss
through lifestyle modification is the primary recommended therapy. It has been shown that
a weight loss of >10% body weight is strongly associated with resolution of fibrosis, however,
in practise, only a minority of patients manage to achieve and sustain this magnitude of
weight loss. Following a statistical analysis whereby all thirty participants were considered,
irrespective of whether they completed the intervention, Chapters 3 and 4 demonstrate that
a very low calorie diet (~800kcals/day) is a safe, feasible and acceptable intervention to
achieve a >10% weight loss in 34% of patients with advanced NAFLD to nine months. Chapter
5 describes differences in levels of physical activity and inactivity between patients with
advanced NAFLD and age- and gender-matched healthy controls, further corroborating the
need for targeted physical activity interventions for patients with NAFLD. Specifically, patients
with NAFLD spent more time inactive, and less time engaging in physical activity of light,
moderate, vigorous and moderate-vigorous intensities than age and gender matched healthy
controls. Chapter 6 describes the development of a tailored exercise programme and an
embedded retrospective cohort analysis, targeting the fitness of patients on the liver
transplantation waiting list, would be acceptable to patients. The retrospective cohort
analysis described clinical measures which are obtained as part of the decision making process
to determine suitability for receiving a liver transplant. Data obtained from the retrospective
cohort analysis demonstrated that poor cardiorespiratory fitness and other “unhealthy”
lifestyle behaviours were major determinants of patients not being wait-listed for liver
transplant.
In conclusion, this thesis suggests that lifestyle interventions could be employed as acceptable
and feasible strategies to achieve weight loss and reduce disease progression in patients with
advanced NAFLD. Furthermore, this thesis proposes that clear, structured recommendations
for lifestyle behaviours be implemented into clinical care pathways for patients with lifestyle related liver disease across the disease spectru
Chirped Pulse Fourier Transform Microwave Spectroscopy of Nitrogen-Containing Organic Molecules
Get PDFPhD ThesisChirped Pulse Fourier Transform Microwave (CP-FTMW) spectroscopy is a powerful
analytical technique. Its versatile applications include molecular structure determination,
generating molecular rotational signatures for astrochemistry and probing weak inter- and
intra-molecular interactions as well as large amplitude motions. For this thesis,
experiments were performed with the CP-FTMW Spectrometer at Newcastle University
operating in the 2.0-18.5 GHz region, featuring a pulsed valve for supersonic expansion
and a laser ablation source for gas-phase generation of non-volatile species.
The microwave spectra of i) phosphine-carboxamide and a van der Waals complex with
argon, ii) two monohydrate isomers of imidazole, iii) methylimidazole isomers and iv)
monohydrate complexes of methylimidazole isomers are reported and analyzed.
Molecular rotations probed in the microwave spectra are directly correlated to the
geometry of these species. Detection of isotopologues, in natural isotopic abundance or by
using isotopically enriched samples, allows for full or partial structure determination and
rationalization of large amplitude motions.
Phosphine-carboxamide is a phosphorus-bearing analogue of urea. Coordination of an
argon atom highlights that the electronic density is concentrated at the amide site. The
monohydrate complexes of imidazole exhibit bifunctional hydrogen bonds with imidazole
acting either as a proton donor or acceptor. The spectra of methylimidazole isomers exhibit
internal rotation of the CH3 group in each isomer. The relative energy required to surmount
the barrier to internal rotation in each isomer is relatable to the position where the CH3
substitutes on the imidazole ring. The barrier depends on the chemical environment and
orbital overlap between the CH3 group and the adjacent C-H bonds. In the monohydrate
complexes of methylimidazole only one type of hydrogen bonding was detected and
internal rotation of CH3 group was observed. Results are supported by ab initio and density
functional theory (DFT) calculations
The Value of Public Goods in Altruistic Societies
Get PDFPh. D. Thesis.This thesis is concerned with the valuation of public goods through the elicitation of preferences
from citizens in society. This thesis explores theoretically and empirically the impact of
different preference sets on the value of a public good, specifically when preferences are
extended beyond one’s own welfare. Three frames for eliciting preferences are considered:
Consumer Frame 1, Consumer Frame 2, and the Citizen Frame. Consumer Frame 1 requires
individuals to take a purely self-interested perspective. This represents the standard
methodology. Consumer Frame 2 allows for altruistic preferences. The Citizen Frame, a novel
methodology, places individuals behind a veil of ignorance based on Harsanyi (1953) to
generate impersonal preferences from personal preferences. The frames are assessed for their
impact on the societal value, individual values, and their appropriateness for cost-benefit
analysis by respecting consumer sovereignty and satisfying the underlying preferences when
aggregated.
The contributions made in thesis are split into two parts. Part I models the three frames using a
model of optimal provision based on Jones-Lee (1991) to assess the societal value and a model
of cost-benefit analysis based on Bergstrom (2006) to assess the individual value and the costbenefit test. In Part II, two laboratory experiments are used to test certain hypotheses from the
theoretical chapters. The results of the experiments support the findings of the theory.
The findings of this thesis suggest that the use of Consumer Frame 1 in preference elicitation
studies should be used with caution as they potentially violate consumer sovereignty. Whilst
Consumer Frame 2 allows altruistic preferences into valuations and therefore respects consumer
sovereignty, the values may not be compatible with the cost-benefit test. The Citizen Frame
offers a novel methodology for individuals to consider both the distribution of benefits and
costs to society and thus include preferences for distributive justice in their valuations.Lomas famil
Heat sinks based on liquid metal for power electronics cooling applications
Get PDFPhD ThesisPower semiconductor devices are key components for efficient power conversion in a wide range
of industrial applications. The continuous trend toward increasing the power capability and
decreasing the chip area of the semiconductors results in the generation of high heat fluxes,
due to the power losses. Also, power electronics are one of the most common components of
the power converter to fail, as a result of the thermomechanical stress within the structure of
power module caused by large junction temperature swings (∆Tj). Effective and efficient thermal
management systems should therefore be employed to dissipate the excess heat to the ambient
environment and reduce the thermomechanical stress.
Liquid metals received little attention as heat transport agents thus far, in spite of their excellent
thermophysical properties. Also, their high electrical conductivity allows for driving them with
a magnetohydrodynamics (MHD) pump, which is a reliable and low–power device. Hence, a
thermal management system based on Ga68In22Sn10 liquid metal coolant is able to remove high
heat fluxes, requires low operating power and provides high reliability; all desirable attributes for
modern power electronic applications.
This thesis focuses on the design and development of a cooling system based on liquid metal for
conventional insulated–gate bipolar transistors (IGBTs), which are the most widely used power
electronic switches for medium–to–high power conversion applications. The proposed heat sink
is attached to the IGBT power module and liquid metal is impinged directly against the baseplate
with the use of an integrated MHD pump, thus eliminating the need for thermal interface material
(TIM). Moreover, an adaptive thermal management method based on liquid metal flow control is
presented that is able to significantly reduce ∆Tj
. Also in this thesis, the design and development
of a liquid metal heat sink for press–pack IGBTs (PPIs) is proposed. Traditionally, water is
used for cooling PPIs in high–power applications. However, ionised particles are developed in
the cooling system that contribute to the corrosion of the piping system. Therefore, the use of
a thermal management system based on liquid metal increases the heat dissipation capability
without corroding the cooling structure. Analytical work is performed on the design of both heat
sinks and the implementation of the temperature control method. The thermal performance of
both heat sinks, as well as the adaptive heat sink control, are experimentally validated
Distributed real-time physics for scalable and streamed games and simulation
Get PDFPhD ThesisIn this study, a solution to delivering scalable real-time physics simulations is proposed. Although
high performance computing simulations of physics related problems do exist, these
are not real-time and do not model the real-time intricate interactions of rigid bodies for visual
effect common in video games (favouring accuracy over real-time). As such, this study presents
the first approach to real-time delivery of scalable, commercial grade, video game quality
physics and is termed Aura Projection (AP). This approach takes the physics engine out of the
player’s machine and deploys it across standard cloud based infrastructures. The simulation
world is divided into regions that are then allocated to multiple servers. A server maintains
the physics for all simulated objects in its region. The contribution of this study is the ability
to maintain a scalable simulation by allowing object interaction across region boundaries
using predictive migration techniques. AP allows each object to project an aura that is used to
determine object migration across servers to ensure seamless physics interactions between
objects. AP allows player interaction at any point in real-time (influencing the simulation) in
the same manner as any video game.
This study measures and evaluates both the scalability of AP and correctness of collisions
within AP through experimentation and benchmarking. The experiments show that AP is a
solution to scalable real-time physics by measuring computation workload with increasing
computation resources. AP also demonstrates that collisions between rigid-bodies can be
simulated correctly within a scalable real-time physics simulation, even when rigid-bodies
are intersecting server-region boundaries; demonstrated through comparison of a distributed
AP simulation to a single, centralised simulation. We believe that AP is the first successful
demonstration of scalable real-time physics in an academic setting
Adult hippocampal neurogenesis as a biomarker of long-term experience in domestic laying hens (Gallus gallus domesticus)
Get PDFPh. D. Thesis.Consideration for the welfare of farmed animals has highlighted the goal of ensuring that they
lead a “life worth living”, comprised of an acceptable balance between positive and negative
experiences. Novel objective biomarkers of long-term or cumulative experience that are
valence-specific may contribute to the assessment of this criterion. In humans, numbers of
surviving hippocampal neurons produced through adult neurogenesis reflect self-reported
mood. In rats and mice, adult hippocampal neurogenesis (AHN) is reliably suppressed by
chronic stress, but stimulated by positive experiences. As AHN in the avian brain also appears
to be downregulated by chronic stress and upregulated by cognitive enrichment, this project
sought to quantify immature neurons in the brains of laying hens with known long-term
experiences, to identify factors likely to have a notable influence on lifetime subjective welfare.
Four studies measured levels of AHN in hens in relation to i) experimental housing conditions,
ii) individual differences in use of outdoor areas, iii) severity of acquired fractures to the keel
bone, and iv) alternative commercial housing systems (enriched-cage versus aviary) and
physical body condition, on-farm. Over the course of the project, a methodological comparison
was made between traditional morphological quantification of immature neurons by
immunohistochemistry, and quantification of the transcription of genetic markers of AHN.
Densities of immature differentiating neurons were suppressed by severe keel bone fractures
and in association with poor feather coverage, low body mass and pale combs. The proliferative
stage of AHN was also positively associated with the time that individual hens within a freerange system spent in the outdoor areas provided. The results suggest that interventions to
reduce the prevalence of keel bone fractures and improve physical condition in commercial
laying hens are likely to have significant benefits for the balance of cumulative chronic stress
and positive affect experienced.Universities Federation for Animal Welfar
Bayesian inference for linear stochastic differential equations with application to biological processes
Get PDFPh. D. Thesis.Stochastic differential equations (SDEs) provide a natural framework for describing the
stochasticity inherent in physical processes that evolve continuously over time. In this
thesis, we consider the problem of Bayesian inference for a specific class of SDE – one
in which the drift and diffusion coefficients are linear functions of the state. Although
a linear SDE admits an analytical solution, the inference problem remains challenging,
due to the absence of a closed form expression for the posterior density of the parameter
of interest and any unobserved components. This necessitates the use of sampling-based
approaches such as Markov chain Monte Carlo (MCMC) and, in cases where observed data
likelihood is intractable, particle MCMC (pMCMC). When data are available on multiple
experimental units, a stochastic differential equation mixed effects model (SDEMEM) can
be used to further account for between-unit variation. Integrating over this additional
uncertainty is computationally demanding.
Motivated by two challenging biological applications arising from physiology studies
of mice, the aim of this thesis is the development of efficient sampling-based inference
schemes for linear SDEs. A key contribution is the development of a novel Bayesian
inference scheme for SDEMEMs
Chipless RFID sensor systems for structural health monitoring
Get PDFPh. D. ThesisDefects in metallic structures such as crack and corrosion are major sources of catastrophic
failures, and thus monitoring them is a crucial issue. As periodic inspection using the nondestructive testing and evaluation (NDT&E) techniques is slow, costly, limited in range, and
cumbersome, novel methods for in-situ structural health monitoring (SHM) are required.
Chipless radio frequency identification (RFID) is an emerging and attractive technology to
implement the internet of things (IoT) based SHM. Chipless RFID sensors are not only wireless,
passive, and low-cost as the chipped RFID counterpart, but also printable, durable, and allow
for multi-parameter sensing.
This thesis proposes the design and development of chipless RFID sensor systems for SHM,
particularly for defect detection and characterization in metallic structures. Through simulation
studies and experimental validations, novel metal-mountable chipless RFID sensors are
demonstrated with different reader configurations and methods for feature extraction, selection,
and fusion. The first contribution of this thesis is the design of a chipless RFID sensor for crack
detection and characterization based on the circular microstrip patch antenna (CMPA). The
sensor provides a 4-bit ID and a capability of indicating crack width and orientation
simultaneously using the resonance frequency shift. The second contribution is a chipless RFID
sensor designed based on the frequency selective surface (FSS) and feature fusion for corrosion
characterization. The FSS-based sensor generates multiple resonance frequency features that
can reveal corrosion progression, while feature fusion is applied to enhance the sensitivity and
reliability of the sensor. The third contribution deals with robust detection and characterization
of crack and corrosion in a realistic environment using a portable reader. A multi-resonance
chipless RFID sensor is proposed along with the implementation of a portable reader using an
ultra-wideband (UWB) radar module. Feature extraction and selection using principal
component analysis (PCA) is employed for multi-parameter evaluation.
Overall, chipless RFID sensors are small, low-profile, and can be used to quantify and
characterize surface crack and corrosion undercoating. Furthermore, the multi-resonance
characteristics of chipless RFID sensors are useful for integrating ID encoding and sensing
functionalities, enhancing the sensor performance, as well as for performing multi-parameter
analysis of defects. The demonstrated system using a portable reader shows the capability of
defects characterization from a 15-cm distance. Hence, chipless RFID sensor systems have
great potential to be an alternative sensing method for in-situ SHM.Indonesia Endowment Fund for Education
(LPDP
Auslander-Reiten theory, derived categories, and higher dimensional homological algebra
Get PDFPh. D. Thesis.Auslander-Reiten theory plays an important role in the study of abelian and triangulated
categories (in classic homological algebra) and in their higher analogues (in the more recent
higher homological algebra). The classic setup studies module categories of the form mod
and their bounded derived categories Db(mod ), where is a nite dimensional algebra
over a eld k and mod is the category of nitely generated (right) -modules.
If gldim B 1, Br uning proved there is a bijection between the wide subcategories of
the abelian category mod and those of the triangulated category Db(mod ). When
T is a suitable triangulated category, J rgensen described Auslander-Reiten triangles in
the extension closed subcategories of T . If X b mod is a precovering extension closed
subcategory, Kleiner proved that any indecomposable not Ext-projective X > X appears
as the end term of an Auslander-Reiten sequence in X and he further described the case
when End (X) modulo the morphisms factoring through a projective is a division ring.
Letting d be a positive integer, we study higher homological algebra and higher Auslander-
Reiten theory. Geiss, Keller and Oppermann generalised triangulated categories to (d+2)-
angulated categories and Jasso likewise generalised abelian categories to d-abelian categories.
Note that the case d = 1 recovers classic homological algebra. Assuming there is a
d-cluster tilting subcategory F b mod , consider
F = add{ idF S i > Z} b Db(mod ):
Then F is d-abelian and plays the role of a higher mod having for higher derived category
the (d + 2)-angulated category F. With this in mind, we generalise Br uning, J rgensen
and Kleiner's results for higher values of d.
We also use higher Auslander-Reiten theory to generalise results on Grothendieck groups
of a suitable triangulated category T . We present \higher cluster tilting" versions of
results by Xiao and Zhu and by Palu and a \higher angulated" version of Palu's result.
Our results express K0(T ) as a quotient of the split Grothendieck group of higher-cluster
tilting subcategories of T .
We prove analogues of results by Kleiner on subcategories of mod in the corresponding
setup of subcategories of a suitable triangulated category T with a precovering extension
closed subcategory C. In particular, we introduce indecomposable Ext-projective objects
C in C, show that such a C appears in what we call a left-weak Auslander-Reiten triangle in
C and prove how these objects are related to the concept of Iyama and Yoshino's mutation.
ContentsSAgE faculty Newcastle Universit
The merging of the goat and thought vowels in Tyneside English: evidence from production and perception
Get PDFPh. D. Thesis.This thesis presents a sociolinguistic investigation into the potential merging of the goat
and thought vowels in contemporary Tyneside English. Following Watt’s (1998)
observation that these two vowels are homophonous for some Tyneside speakers, the
main study examines the extent to which goat and thought are found to overlap in
both speech production and speech perception. Given the lack of previous research on
this sound change, evidence from sociolinguistic interviews and experimental perception
tasks are evaluated here in order to determine whether there is a current
goat-thought merger-in-progress in Tyneside.
The speech production data is made up of conversational interviews with 28 speakers,
obtained from the Diachronic Electronic Corpus of Tyneside English. An acoustic analysis
was performed on this interview data in order to assess the merging of goat and thought
in phonetic space. Both static (one-measurement) and dynamic (vowel trajectory) data
were collected, and several different measures of merger were employed in the analysis.
Results showed that many speakers exhibit considerable overlap of goat and thought
in the vowel space due to a lowering of the goat vowel, while findings from Pillai scores
and Generalised Additive Mixed Models indicated that young females have the greatest
overlap between the two vowels.
For the investigation into how goat and thought are perceived in Tyneside, 43
listeners took part in a vowel perception experiment. Discrimination and identification
tasks were carried out so that listeners could be assessed on their ability to distinguish
and categorise these vowels. Using measures of accuracy, sensitivity, and reaction time,
results showed that listeners were significantly less accurate and significantly slower in
responding to goat-thought trials than to trials containing control stimuli. Such
findings suggest some degree of perceptual confusability between these two vowels for the
Tyneside listeners, and provide further evidence of the merging of goat and thought
in the speech community.
Comparing the results of the production and perception analyses, the overall findings
indicated that goat and thought are merging in Tyneside. However, some evidence
of goat-fronting is also found in both the production and perception data, which may
prevent further progression toward a full phonemic goat-thought merger in Tyneside
English.Economic and Social Research Council (ESRC