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An investigation of selective constraints in colorectal cancer
Get PDFNext generation sequencing (NGS) has significantly advanced our understanding of colorectal cancer (CRC) and highlighted the inaccuracies of the traditional, linear model of adenoma-carcinoma evolution. NGS has provided evidence for intra-tumour heterogeneity (ITH) and colorectal carcinomas that lack a full complement of driver mutations. Alternatively, the branched model of adenoma-carcinoma evolution proposes that genetically differing clones can coexist and evolve in spatially discrete areas. Further refinements such as the just-right model and mini-driver models are encompassed by the branched model, providing additional insights.
By examining mutations in multi-regional, colorectal adenomatous polyp samples, I have provided supporting evidence for the branched model of CRC evolution. Following an assessment of the presence of parallel evolution in adenomas, I looked specifically at mutations in Wnt pathway genes to determine whether there is evidence for a “just-right” level of pathway activation by mutations. Canonically, the Wnt pathway is central to epithelial cell growth and regulation in the intestine. When mutationally activated, this pathway can lead to uncontrolled neoplastic initiation and progression. Previous evidence from familial adenomatous polyposis (FAP) suggests that a just-right number of APC 20-amino acid repeats results in an optimal level of Wnt pathway activation. The applicability of this model to the entire Wnt pathway has been suggested. The mini-driver model proposes that low-frequency mutations of minor selective advantage, compared with major-driver mutations, can finely adjust Wnt activation levels to provide a just-right level of Wnt signalling. Using a large, CRC dataset (100KGP), I explored mutations in both major-driver and mini-driver genes, seeking patterns of mutual exclusivity and co-occurrence. The results supported the just-right model, revealing mutual exclusivity between mutations in major-driver genes and co-occurrence between mutations in major-driver and mini-driver genes. These results suggested that combinations of Wnt pathway mutations are selected to provide a just-right amount of Wnt signalling for a tumour to evolve. In addition, this study also found potential discrepancies between particular combinations of mutations in different tumour genomic instability subtypes (MSS/MSI) and in different anatomical locations, which was suggestive of differing just-right signalling levels depending on the genomic instability/location context of the tumour. Furthermore, the proposed role of TCF7L2 as a mini-driver, and CRC predisposition gene, was investigated through genome-wide association studies (GWAS) and mouse model studies, showing some supportive results.
This research contributed valuable insights into the complex dynamics of CRC evolution, shedding light on the role of the just-right model involving the Wnt pathway and supporting the branched model of adenoma-carcinoma evolution
Approaches to optimising care for women with gestational diabetes mellitus in the UK
Get PDFGestational diabetes mellitus (GDM) is the most common pregnancy complication, affecting one in six pregnancies globally. It is associated with both short- and long-term health risks for mothers and offspring, including adverse perinatal outcomes and an elevated risk of developing future obesity, type 2 diabetes, and cardiovascular disease. While effective screening, diagnosis, and blood glucose management can mitigate these risks, there remains no consensus on the optimal strategies for addressing GDM.
This thesis, based on research conducted between 2020 and 2023, investigates approaches to optimise care for women with GDM. The primary focus is a multi-methods study exploring the impact of enforced changes in clinical management during the SARS-CoV-2 pandemic. Additionally, it presents a systematic review assessing the potential of precision markers for improving GDM outcomes.
The introduction offers a review of the literature on GDM screening, diagnosis, and management, with a particular focus on the modifications to clinical care precipitated by the pandemic. The subsequent three chapters present the key findings of this research.
Chapter 1 presents a retrospective multicentre cohort study examining the impact of pandemic-related changes in GDM diagnostic criteria and care provision on pregnancy outcomes. This study compares data from 4,915 women diagnosed with GDM prior to the pandemic (April 2018 – March 2020) with data from 3,467 women diagnosed during the pandemic (April 2020 – March 2021) across nine NHS trusts and health boards. The new diagnostic criteria more often identified women with GDM who were multiparous, had a higher BMI, and came from more deprived backgrounds, while fewer had a history of GDM (all p<0.05). During the pandemic, key pregnancy outcomes remained stable despite changes in screening and diagnostic thresholds.
Remote care was found to be as effective as traditional in-person care, even for higher-risk women identified during this period.
Chapter 2 explores the experiences of healthcare professionals delivering multidisciplinary GDM care during the pandemic through a qualitative interview study. Participants (n=23 from three sites, representing members of the multidisciplinary team including diabetes specialist nurses, midwives, dietitians, diabetologists, and obstetricians) highlighted pre-pandemic inefficiencies in care delivery. Remote care adaptations—including virtual glycaemic management and task-shifting to allied health professionals—were generally viewed positively, facilitated by mobile technologies. However, remote care posed challenges for women with language barriers, and healthcare professionals reported increased isolation and concerns about the sustainability of virtual care due to burnout and limited IT infrastructure. A hybrid model combining in-person and remote care emerged as the preferred solution.
Chapter 3 investigates precision medicine approaches in GDM care through two systematic reviews. Although studies on precision lifestyle interventions were scarce, several clinical markers, such as a history of GDM, BMI, and blood glucose levels at diagnosis, were identified as potential predictors of the need for pharmacological intervention.
In summary, this thesis highlights several strategies for optimising GDM care in the UK. Key findings from the pandemic include the rising incidence of GDM, the potential for adjunct screening tools to better detect overt diabetes and reach marginalised women, and the effectiveness of remote antenatal care. Beyond existing approaches, precision methods may refine treatment pathways by enabling earlier identification of women requiring escalated care
Communication and complexity: layperson decision-making in the Scottish Children’s Hearings system
Get PDFThe Children’s Hearings system is a unitary, non-court-based legal tribunal system responding to child protection and youth justice concerns in Scotland. Decision-making is undertaken by three lay volunteers called panel members, and the participation of children and young people is viewed to be central to the process. Despite the importance of the decisions being made, there has been little examination of how panel members experience the decision-making process or how it can be theorised.
An ethnographic research methodology was employed to explore how panel members make decisions and what helps or hinders the process. Observations of 67 children’s hearings and pre-hearing panels, and qualitative interviews with 20 panel members, were undertaken. Panel member decision-making involves two key processes; making sense of and forming judgements based on information presented in advance of a hearing, and exploration of this information in the context of a face-to-face meeting with the child, parents, social worker and other relevant people. Findings highlight the crucial role of written reports in preparing panel members for a hearing and the barriers to effective communication, the centrality of emotion and the need for panel members to manage their own and others’ emotional responses, and the importance of language use and interactional competence in managing hearings skilfully. These features affect how children’s views are heard and considered in hearings.
This study addresses a gap in the literature by providing a detailed examination of the communicative and interactional processes central to panel member decision-making and locating these findings within wider judgement and decision-making frameworks. Recommendations aimed at supporting the decision-making process are proposed. The findings make a contribution to current knowledge and understanding of decision-making in child welfare proceedings and how lay decision-makers make sense of and reach decisions regarding the care of a child
ICESat-2 measurements of forest structure & their utility for driving large-scale albedo simulation
No full textForests are a vital part of the Earth system, with many processes depending on their distribution and structure. The ICESat-2 spaceborne lidar mission collects global measurements of 3D structure, with potential applications in radiative transfer modelling, biomass mapping, biodiversity assessment and more. However, the ICESat-2 mission currently processes only canopy height and Relative Height metrics in its vegetation product, which limits the utility of ICESat-2 data in many fields. In this thesis, I assess how measurements of additional stand-level Plant Structural Traits (PSTs) like canopy cover and Plant Area Volume Density can be extracted from data collected by ICESat-2. I go on to test the applicability of such measurements to the challenge of land surface albedo modelling over boreal forest.
In Chapter Two, I explore how to extract the input parameters required for the calculation and interpretation of canopy height, canopy cover, Relative Height (RH) metrics and Plant Area Volume Density (PAVD) from data collected by ICESat-2. In particular, I investigate how the ratio of canopy and ground reflectances - key variables for the accurate estimation of these stand-level PSTs - can be estimated. I demonstrate that it is possible to calculate the canopy:ground reflectance ratio at site scale from ICESat-2 data with accurate photon classification.
In Chapter Three, I apply these canopy:ground reflectance ratios to simulate ICESat-2 data from discrete-return Airborne Laser Scanning (ALS) data at five sites. I calculate canopy height, canopy cover, RH metrics and PAVD profiles from this simulated ICESat-2 data and compare these with the same PSTs calculated from colocated data collected by ICESat-2 itself. As ALS is known to be sensitive to these stand-level PSTs, similarity between simulated and observed ICESat-2 metrics shows that ICESat-2 is sensitive to PSTs where the canopy:ground reflectance ratio is well constrained.
In Chapter Four, I assess whether ICESat-2 canopy height and cover can be used to drive the implicit 3D SPARTACUS radiative transfer model to simulate land surface albedo over boreal forest in Finland. I find that, while SPARTACUS is able to simulate the full range of land surface albedo values observed by MODIS, driving it with ICESat-2 canopy height and cover does not offer an improvement over the more simple Sellers two-stream radiative transfer model. However, I identify mapping of snow cover and Clumping Index as key areas where ICESat-2 measurements could aid in improving the modelling of land surface albedo.
This thesis concludes that ICESat-2 is sensitive to canopy structure and can be used to retrieve measurements of canopy cover and Plant Area Volume Density alongside the canopy height and Relative Height metrics currently offered by ICESat-2. Correction for canopy:ground reflectance ratio is necessary to minimise bias in these PST measurements. Using ICESat-2-derived canopy height and cover to drive an implicit 3D radiative transfer model does not offer improved land surface albedo simulation compared with a more simple two stream model. However, ICESat-2 PST measurement could contribute to land surface albedo modelling through use for snow mapping, alongside potential contributions to many other fields such as biodiversity assessment, fire risk mapping or aboveground biomass measurement
Review of demand for hydrogen derivatives and products
Get PDFThis report reviews the possible demand for hydrogen derivatives and products from hydrogen production in Scotland. Offtake sectors and countries as well as domestic demand are reviewed and policy gaps are considered
Blind detection and estimation for integrated sensing and communications
No full text[ A B S T R A C T : R e d a c t e d
Exploring childrens’ understanding of overweight and obesity: a qualitative study in Santiago, Chile
No full textThis thesis explores the understanding and experiences of overweight and obesity in children aged 10-12 from 3 clinics located in a deprived area in Santiago, Chile. Overweight and obesity are considered to be a risk to the health of both individuals and the population as a whole. Indeed, in the last three decades, overweight and obesity have been framed as an ‘epidemic’ and linked to severe risks and comorbidities such as diabetes, cardiovascular disease and cancer. There is a high prevalence of overweight and obesity in Chile, and public health strategies have been developed to address this. Particular concerns have been raised about children. According to the last report from the Subsecretaria de Salud Publica (2023), 58.3% of Chilean children are categorised as ‘overweight’ or ‘obese’. Despite the country’s economic growth, social and health inequalities remain among the child population in terms of the distribution of overweight.
Most studies on childhood obesity are epidemiological, quantitative studies that provide information on biomarkers, trends in Body Mass Index, and health risks. However, there are gaps in the existing research that this thesis sought to address. This research is need it for several reasons: first, there is limited insight into the perceptions and experiences of children who have been clinically labelled as obese. Second, while some research has addressed the views of parents in relation to children’s overweight, it is less common for these views to be sought alongside the views of their child. Third, much research on childhood obesity comes from the Global North. Considering these gaps, this research explores overweight and obese children’s and mothers’ meanings of health, and weight, and their everyday Health-Related Practices (HRPs) related to weight to make potential contributions to public health strategies regarding overweight and obesity in children.
This qualitative study, conducted in Santiago between March and September 2021, involved 34 semi-structured online separate interviews with children aged 10-12 who were classified as ‘overweight’ or ‘obese’ (N=18) and their mothers (N=16). Participants were recruited from 3 clinics (ANCORA). Children and mothers were each interviewed once. Due to the COVID-19 lockdowns, interviews were conducted online, and different participatory methods and prompts were used to encourage participants’ engagement. The methods used to explore meanings of bodies, weight and HRPs with dyads provided insights into complex perspectives of child-mother dyads and family dynamics, shedding light on relational aspects and differing levels of children’s agency. The use of participatory methods in interview design and the approach to online data collection facilitated the exploration of sensitive topics with children and caregivers. Employing Reflexive Thematic Analysis, the researcher analysed the interview data, drawing on relevant concepts from the sociology of health and illness, and the sociology of childhood, to interpret the accounts of children and mothers. The analysis explored the children’s accounts collectively, but also looked at the child/mother dyads to uncover any shared accounts, gaps or silences.
The thesis presents five key findings. First, children’s descriptions of their bodies differed from the medical terms ‘overweight’ and ‘obese’. None of the children and only one mother used the term ‘obese’. For most children and mothers, ‘overweight’ labels were not significant in terms of having a ‘disease’ or an ‘ill health’ condition that may be ‘treated’. Children’s meanings of growth and weight were shaped by social interactions that contextually shaped their perspectives of their own weight and body, focusing on appearance rather than health.
Second, children faced weight stigma and experienced negative emotions associated with weight-shaming from clinicians, peers and relatives. In clinical settings, children reported becoming more aware of their body size, and most began to perceive their bodies as ‘different’. How others evaluated weight was relevant to the children, particularly when someone else noticed that being ‘overweight’ was a ‘problem’.
Third, children’s HRPs related to food and physical activity (PA) were understood as individual responsibilities and medicalised practices to lose weight. Children and mothers engaged in weight monitoring and surveillance practices, often with perceived emotional impacts. Strategies such as food type and quantity restriction were commonly used to achieve or maintain a ‘healthy’ weight. PA was predominantly described as an activity to burn calories and lose weight, rather than for general health or well-being.
Fourth, findings demonstrate that social determinants of health (SDoH), such as socioeconomic circumstances, gender, and living and working conditions, influenced food choices and PA opportunities. For instance, lack of income or unemployment constituted critical barriers to achieving the required ‘healthy diet’, while material circumstances, such as housing and home environments, also determined PA opportunities.
Fifth, children and mothers understood public health messages from interventions such as front-of-pack labelling (FOP) and the ‘Choose to live healthy’ strategy. However, they experienced barriers to adopting these interventions due to socioeconomic factors and family dynamics.
This thesis provides insight into children’s views on overweight and obesity, and the HRPs adopted to address their weight. It emphasises the importance of understanding children’s meanings and experiences, and their implications for public health and practice: first, clinics should move towards a health approach that is not focused exclusively on weight and aims to reduce weight stigma; second, clinicians should consider how best to engage with children as individuals, encouraging them to be more involved in decision-making about their own health; third, clinicians should consider children’s everyday routines, and not assume families are all the same; fourth, clinicians should seek to be aware of families’ social and economic contexts when recommending changes to diet and PA. By considering children’s and mother’s experiences and meanings of health, growth, weight, and everyday family HRPs, it is possible to present a more complex picture of, and challenge the assumptions around, health, growth, weight, and HRPs in the context of overweight and obesity
Overview of the Jameel Observatory for Food Security Early Action
Get PDFPresented by Alan Duncan and Nathan Jensen at the Jameel Observatory Community of Practice meeting, Addis Ababa, 13-14 May 202
Next-Generation Earth Observation (EO) for Anticipatory Drought Risk Management in East African Pastoral Drylands (N’GOMbE)
Get PDF‘Lightning talk’ presented by Francesco Fava (University of Milan) at the Jameel Observatory Community of Practice meeting, Addis Ababa, 13-14 May 202
Reducing the impacts of disasters in Somalia using the anticipatory action framework
Get PDF‘Lightning talk’ presented by Mohamed Beegsi (Save the Children) at the Jameel Observatory Community of Practice meeting, Addis Ababa, 13-14 May 202
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