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A Diagnostic Procedure for Identifying Isotherm Models in Liquid Chromatography
No full textLiquid chromatography is a pivotal purification process widely used in pharmaceutical development and manufacturing. Efficient optimal design and control of the process rely heavily on mechanistic models such as the lumped pore diffusion model (POR) and the Equilibrium Dispersion Model (EDM), both popular choices owing to their simplicity and good accuracy for a wide range of applications. However, the choice of the functional form of the isotherm models, which describe the component adsorption equilibria, strongly affects the predictions of the chromatography model. While traditional isotherms perform well for simple compounds (e.g., small molecules), they often fall short for more complex separations (e.g., peptides), thus resulting in process-model mismatch, even following rigorous parameter estimation. As a remedy to this, recent advances have introduced hybrid models that integrate data-driven elements to improve the predictive accuracy, although at the cost of loss of process insight, low interpretability, and increased complexity. To address the process-model mismatch in chromatography, we have proposed a model diagnostic procedure, adapted from a diagnostic framework in kinetic models, based on a Lagrange multiplier test, to refine isotherm models that initially underfit. The procedure is demonstrated by three in-silico case studies, showing improved accuracy against experimental data without having to resort to black-box models, thus providing models that retain physical insight
‘Hanger’ and beyond: Measuring hunger-related mood dysregulation and its links with mental health, functioning and task-based mood induction
No full textBackground: Some people experience mood changes when hungry. However, the relevance of this phenomenon to clinical conditions, such as depression, anxiety and eating disorders, is understudied. Therefore, we devised a questionnaire to measure hunger-related mood dysregulation. / /
Methods: We developed and validated the Mood, Emotions and Appetite List (MEAL) using exploratory and confirmatory factor analysis in adults and adolescents in the community, and adults with a history of mental health disorder (N = 1119). We examined the association of MEAL scores with happiness, frustration and boredom during the frustration-inducing mood drift task, in which participants wait for six minutes and rate their mood every 30 s. / /
Results: The MEAL showed good psychometric properties, capturing three factors for hunger-related ‘irritability’, ‘low mood’ and ‘somatic feelings’ (RMSEA = 0.03 in community adults, 0.05 in community adolescents, 0.08 in adults with mental health disorder history). Quantitative and qualitative responses evidenced that hunger-related mood dysregulation impacts relationships, work and hobbies. MEAL scores were associated with irritability, depression, anxiety and menstrual symptoms. In the mood drift task, the irritability subscale (MEAL-i) demonstrated a significant interaction with time, such that individuals with higher MEAL-i scores reported steeper decreases in happiness ( = −0.11; 95 % CI: −0.16–-0.06) and steeper increases in boredom ( = 0.06; 95 % CI: 0.00–0.12) and frustration ( = 0.12; 95 % CI: 0.05–0.19). / /
Conclusions: The MEAL measures individual differences in hunger-related mood dysregulation, is associated with mental health, self-reported functioning, and predicts faster worsening of mood during experimentally induced frustration
Understanding China through Digital Anthropology
No full textUnderstanding China through Digital Anthropology questions our understanding of digital technologies by demonstrating fundamental differences in the meaning of both technology and the digital between China and the West. This follows from a longstanding historical divergence in the meaning of and attitude to the relationship between technology and humanity.
The book also challenges our understanding of China through a series of case studies that range from the creation of algorithms, the normative basis of social media and the impact of digital communication on diverse fields including economic practices, gender, media and healthcare. These further demonstrate the value of long-term ethnographic studies that situate people’s online activities in their everyday offline lives. These case studies are testimony to the continued heterogeneity of China in covering sophisticated urban IT professionals, Tibetan villagers and grassroots women struggling to make a living. All of this contributes to a new understanding of a contemporary China that has been transformed by the sheer scale and dynamism manifested in the deployment of digital technologies. The book also includes an extensive summary of work undertaken by scholars inside China on digital anthropology and previously only available in Chinese
Characterisation of dynamic catalytic surfaces for small molecule reduction using grazing incidence techniques
No full textResearch into heterogeneous catalysis focuses on elucidating the nature and reactivity of surfaces, as well as understanding the influence of properties such as particle size, surface area, morphology (such as preferred crystal growth planes), dispersion, and metal-support interactions (MSI). The work featured in this thesis contains the results from the study of two model planar catalytic systems of industrial interest. Due to minimal amounts of ‘active material’ on planar substrates, surface-sensitive X-ray techniques are essential for their characterisation, therefore this study employs synchrotron radiation, namely Grazing Incidence X-ray Diffraction (GIXD) and X-ray Reflectivity (XRR), to examine 2D models in situ including Cobalt catalysts during reduction-oxidation-reduction (ROR) cycles and Fischer-Tropsch Synthesis (FTS), as well as thin film supported Palladium catalysts during acetylene hydrogenation under operando conditions.
GIXD data reveals support-dependent variation in Cobalt’s reducibility and polymorph formation, with all samples forming more Co face-centred cubic (FCC) than hexagonal close-packed (HCP) polymorphs. A Scherrer analysis of FTS catalyst regeneration shows that on TiO2 and α-Al2O3 supports, larger Co nanoparticles re-oxidise while smaller ones remain metallic, suggesting that a strong MSI is not the sole influence on structural evolution. The ROR cycle’s importance is stressed as the results confirm ‘active’ Cobalt can be freed from TiOx encapsulation phenomena.
Thin film Pd-catalysts were studied to determine the presence of PdZn and PdC during acetylene hydrogenation. Analysis of GIXD, XRR, and online mass spectrometry data revealed that favourable acetylene conversion on Pd/ZnO/Si catalyst requires active Pd, PdC0.05, and β-PdZn with ZnO, with catalytic stability depending on early-stage β-PdZn formation and a high Pd:ZnO ratio. Studies using a redesigned high pressure reactor on Pd/SiO2 catalysts showed PdC0.05 as the most active and selective phase for ethylene at both ambient pressure and but particularly at 5 bar and at 90°C
Using Multi-Modal Quantitative MRI to Investigate the Mechanisms of Brain Injury in Sickle Cell Disease
No full textThis thesis aimed to investigate cerebral injury in Sickle Cell anaemia (SCA), a complex disease with interdependent mechanisms underpinning acute injury and cognitive difficulties in adults and children. Quantitative Magnetic Resonance Imaging (MRI) allows exploration of various aspects of SCA pathophysiology. Haemodynamic compromise occurs when the compensatory mechanisms of oxygen-delivery to tissue fail. Imaging of cerebral haemodynamics is difficult in clinical settings as reference standard 15O PET requires on-site radionuclide production, rarely feasible and unethical in children and vulnerable adults. MRI methods offer a non-invasive option to explore the difference in haemodynamic parameters between SCA participants and healthy controls of all ages as well as monitoring disease progression. QQ (Quantitative Susceptibility Mapping + quantitative Blood Oxygenation Level Dependent MRI; QSM + qBOLD) is an MRI analysis method validated against PET in adults offering analysis of regional changes in cerebral haemodynamics. Oxygen extraction fraction estimated via QQ was increased in both adults and children with SCA compared to healthy controls. Cerebral blood flow, estimated via pseudo-continuous Arterial Spin Labelling, was elevated in children not adults with SCA compared to healthy controls. Estimation of Cerebral metabolic rate of oxygen utilisation (CMRO2) was possible with the addition of arterial oxygen content, which was stable across both SCA and controls. Studies of the connection between white ma[er (WM) integrity and cognition have been limited to diffusion-based MRI methods invalid in brain regions with complex fibre geometry. In this thesis I explored the use of a novel method modelling the individual fibre bundles within a voxel, Fixel-based analysis. Although there was no widespread significant difference in WM between SCA participants and controls, or correlation with cognition, fixel-based metrics detected a change in fibre-cross section with age. Measurement of cerebral haemodynamics and WM integrity in SCA may allow understanding of mechanisms, potentially enabling new treatments
A Genealogy of Security and Education. History, Policies, and Experiences in the Chilean Context
No full textThis research examines the historical and political entanglements between education and security in Chile from the late nineteenth century to the present — a relationship that has remained underexplored despite its relevance to contemporary educational policy and debate. The central contribution of this thesis lies in offering a genealogical account of how schools, often understood as spaces of inclusion and learning, have simultaneously functioned as vectors for managing risk, regulating conduct, and governing populations mobilised in the name of collective protection and securing the future. Drawing on Foucauldian studies of governmentality, the research analyses school practices through the axes of knowledge/truth, normativity, and subjectivity, configuring what is described as a “security dimension” that has shaped educational experiences. The study combines archival analysis with empirical fieldwork in Chilean schools, engaging with policy documents, media discourse, and first-person accounts from students and psychosocial professionals. This multiple methods approach enables a situated understanding of how past rationalities persist and mutate in present-day concerns around security. Findings show that schools have historically operated as strategic sites within a broader security dispositif, responding to perceived threats such as racial degeneration, abnormal childhood, moral disorder, delinquency, and later, psychological distress, violence, and sexuality. These risks were mediated by expert knowledge — hygiene, psychology, criminology, mental health — and managed through institutional mechanisms of classification, surveillance, and intervention. In contemporary contexts, these legacies re-emerge through disciplinary routines, monitoring tools, and therapeutic frameworks that portray students as both vulnerable and potentially threatening. Schools translate diffuse anxieties into concrete procedures of governance. Challenging dominant framings of schooling, this perspective opens new lines of inquiry into the political functions of education, while contributing to the sociology and history of education — particularly within the Global South — offering conceptual tools to rethink educational policy in areas such as inclusion, wellbeing, and securitisation
Naming Sexuality: A Queer Exploration of Proliferating Labels and Playful “World”-Travelling
No full textThis thesis argues that the proliferation of sexuality labels, alongside a culture of playful self-labelling, should be endorsed if we are invested in improving queer lives. Recent years have seen a growing trend towards the invention of new terms that highlight diverse aspects of sexuality. This has been met with both enthusiasm and resistance: while many within queer communities affirm these emerging labels, leading to wider social and institutional recognition, others express concern that they generate conceptual confusion or lack legitimacy. Critics also raise ethical objections, including concerns about political consequences and the constraining nature of identity categories. Chapter One addresses the claim that new terms do not name real sexual orientations. Drawing on literature about the nature of sexual orientation, I show that the concept itself is highly contested, making it difficult to dismiss new categories as illegitimate by appeal to a fixed definition. Chapter Two responds to the criticism that emerging labels do not represent real sexual identities. Through engaging with the relevant literature I reveal four key dimensions of sexual identity: desire, identification, social position, and ways of being. I argue that sexual identity should be theorised as a cluster of distinct phenomena, rather than a unified concept. On this view, it is difficult to straightforwardly dismiss emerging labels as illegitimate. Chapter Three considers the ethical implications of label proliferation. While new terms can offer hermeneutic benefits, they also risk constraining individuals and undermining political progress. I draw on María Lugones’ concept of playful “world”-travelling to argue that we can navigate these risks while preserving the benefits. I conclude that both the proliferation of sexuality labels and a playful approach to self-labelling should be endorsed as valuable for the flourishing of queer lives
On Reconstructing Single-Cell Cancer Evolutionary Histories
No full textCancer is the result of a complex evolutionary process during which cells accumulate genetic and non-genetic alterations over time. Investigating the evolutionary patterns of these alterations is key to revealing mechanisms that drive disease progression and to improving therapeutic approaches. Most previous cancer evolutionary studies have relied on bulk sequencing, which averages signal from thousands of cells and is thus primarily powered to detect early, high-frequency alterations. Yet small subpopulations, or clones, of cells often play a key role in progression, indicating that later, low-frequency alterations can be mechanistically important.
In this thesis, I demonstrate how recent, scalable single-cell whole-genome DNA sequencing (scDNA-seq) overcomes these limitations and enables novel insights into cancer evolution. I present a novel primary–metastasis–matched non-small-cell lung cancer patient scDNA-seq dataset containing thousands of individual cells. To analyse the evolutionary patterns in this dataset, I introduce a statistical framework to infer the evolution of both genetic and non-genetic alterations in single-cell cancer clones. I apply this framework to reveal that the metastatic potential of certain clones may be associated with non-genetic rather than genetic alterations. This demonstrates the value of single-cell clone evolutionary analysis, yet it does not resolve which alterations occur together within individual cells or in the smallest clones.
Therefore, to fully exploit native single-cell resolution, I developed PHANTOM, a novel statistical algorithm that reconstructs single-cell evolutionary histories. Through extensive benchmarking, I demonstrate that PHANTOM enables evolutionary reconstruction with high accuracy from scDNA-seq data, in contrast to previous state-of-the-art approaches. Applying PHANTOM to a large cohort of more than 60,000 cells across multiple tumour types, I reveal that both genetic and non-genetic factors, including DNA-repair defects, reshape cancer evolution.
Together, these datasets, algorithms, and analyses advance our understanding of single-cell cancer evolutionary histories
Investigating Holocene Changes in Deep North Atlantic Circulation Using High Accumulation Rate Marine Sediment Cores
No full textIn this thesis, the variability of North Atlantic Deep Water (NADW) – an important component of global ocean circulation – is investigated throughout the Holocene (0 to 11.7 thousand years before present (ka BP)), using high accumulation rate marine sediment cores.
Firstly, neodymium isotopes are used to reconstruct watermass structure at Cape Hatteras at depths of 1.5 – 3.9 km. While limited by endmember changes and the local influence of the Gulf Stream, the results suggest that the structure of the Deep Western Boundary Current (DWBC) was stable on millennial timescales over at least the last 6000 years.
High resolution sortable silt records from the upper-DWBC at Cape Hatteras are generated and compiled alongside a record from 2.3 km water depth in the Iceland basin. These records are used to investigate the multi-decadal to millennial variability of flow strength within and upstream of the DWBC. Long-term trends in the upper-DWBC (i.e., Labrador Sea Water, LSW) followed inferred subpolar gyre (SPG) strength changes, including large-scale shifts in the early and mid-Holocene. The influence of multi-centennial to millennial scale solar variability is also apparent. At times, the position of the Gulf Stream may impact flow speed at some Cape Hatteras sites.
Based on a new synthesis of deep North Atlantic proxy records and new benthic-planktic 14C measurements from the Iceland Basin, it is estimated that NADW weakened by no more than ~20% during the 8.2 ka BP cold event. The small magnitude of NADW change suggests additional climate mechanisms may have contributed to the cooling. It was also demonstrated that low benthic foraminiferal δ13C events in the subpolar North Atlantic may be attributable to changes in local productivity, rather than a shoaling of NADW. This finding compromises previous interpretations of low benthic δ13C events, especially those used to infer instability of NADW strength during previous interglacial periods
Smart wearable sensing systems mediating the digital monitoring of Loneliness – A review
No full textAs mental health difficulties are of increasing concern and people are encouraged to communicate their feelings, loneliness has become a critical issue for the community, with the number of people identifying as lonely being higher than ever. Loneliness can lead to conditions ranging from simple changes in social behaviors to adverse health situations, with depression and anxiety being the dominant ones. These conditions are known to trigger a cascade of emotions then translated into alterations of physiological signals which can be detected and monitored with digital means, such as wearable sensors. The purpose of this work is to review the smart wearable sensing systems that have been used for the detection of these conditions and the recent advances in the development of these sensors. We first review the physiological signals associated with each one of the main loneliness manifestations, then we present the real-life studies performed involving participants and the use of wearable sensors and subsequently we analyze the main categories of sensors used in the studies, the technological advances and the remaining drawbacks for each one of them. Through this review we managed to examine thoroughly the current smart wearable sensing systems on digital monitoring of loneliness and to identify the most promising fields for development