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Evidence synthesis of population health interventions: syntheses and advancing methods
Get PDFEvidence synthesis of population health interventions often involves managing data from complex interventions and a diverse range of study designs, presenting challenges in applying synthesis methods to provide meaningful results. The work presented here provides examples of population health syntheses and research aimed at improving the conduct and reporting of both synthesis methods and primary studies that are used in syntheses.
An initial essay provides a background on population health intervention evaluations and considers the implications, challenges and value of synthesising population health evidence. An overview of methods to develop guidance examines approaches to achieving consensus and the importance of supporting and managing the project team during guidance development.
Three themes address evidence synthesis of population health interventions. In Theme 1, two reviews demonstrate the use of appropriate methods rigorously applied to population health evidence. The reviews examined the health impacts of social policies, mandatory participation in employment related programmes and participatory budgeting. Conducting these and other reviews developed my experience and ability to contribute to the projects in the following two themes.
Theme 2 discusses three papers that advance systematic review methods by investigating and developing guidance on how to conduct and report synthesis robustly and transparently. The first paper provides guidance for conducting a systematic review of theories, illustrated and discussed using a worked example. The remaining two papers focus on narrative synthesis methods in systematic reviews. One is a methodological study to determine the adequacy of reporting of narrative synthesis of quantitative data in systematic reviews of population health interventions. This led to the third paper, guidance for reporting synthesis without meta-analysis (SWiM), an explanation and elaboration of nine checklist items designed to prompt systematic review authors to include key information when reporting the synthesis of quantitative effect data.
Theme 3 consists of two sets of methodological guidance developed for reporting and conducting population health studies, both relevant for evidence synthesis. TIDieR-PHP is a guideline for reporting population health and policy interventions. Precise descriptions of interventions are crucial for synthesis and TIDieR-PHP prompts users on how to capture the features of interventions that are delivered to, or experienced by, large groups or populations, such as the policies examined in Theme 1. The second paper is guidance for using natural experiments to evaluate population health interventions. The guidance aims to prompt improved conduct and reporting of population health interventions, which is crucial to synthesising evidence of these interventions
Benefits of supplementation with LCn-3 PUFA during diet-induced body mass loss and maintenance phases on body composition, muscle function, and appetite
No full textAbstract not currently available
Spatial variability of meander characteristics in an avulsing distributive fluvial system
Get PDFPrevious studies of meandering fluvial systems have mainly focused on meanders at a localised ‘reach’ scale within a river system, without consideration of the spatial context. As such, much of the research has focused on exhumed meander deposits instead of active meanders. More research is therefore required on the spatial variability of meander deposits across a single system or sedimentary basin. Recent research has found meandering fluvial systems to be a dominant planform type in modern-day sedimentary basins; meander deposits are consequently assumed to be more dominant than originally perceived in the fluvial rock record. Distributive fluvial systems (DFSs) have also been shown to dominate sedimentation patterns in modern-day aggradational sedimentary basins and therefore warrant further study due to their abundance. Due to the prevalence of meandering systems and distributive fluvial systems in modern-day sedimentary basins, this study aims to fill a critical literature gap with regards to the spatial and temporal variability of meander characteristics across a modern-day distributive fluvial system (i.e., from apex to toe of a DFS). This study uses satellite imagery of Brazil, acquired through Google Earth Engine and analysed in ArcGIS software, to conduct a spatial analysis of the meandering Taquari DFS. The Taquari DFS is a well-documented, dominantly meandering system, which provides a good spatial context for the study of meander characteristics across the DFS. Spatial changes in: channel width, channel belt width, meander deposit dimensions and sinuosity are quantified on the Taquari DFS to explore downstream changes in meander characteristics within this system. Polygons are created in ArcGIS using the available satellite imagery, which allows for detailed measurements of meander dimensions downstream. This study also explores the temporal changes in channel width, channel belt width, meander deposit dimensions, and sinuosity on the Taquari DFS since the initiation of the large Caronal avulsion (initiation between 1996 to 1997) by comparing meander dimensions pre-avulsion and during-avulsion. The Caronal avulsion is ongoing and continues to divert flow from the parent channel to the avulsed channel. Using the oldest and most modern satellite imagery available from 1985 and 2022, respectively, fluvial dimensions are compared between pre-avulsion (1985) and during-avulsion (2022) imagery, to understand the impact of the avulsion on the parent channel (active channel) and its associated channel belt and meander deposits. On the modern Taquari DFS (2022), active variables (i.e., active channel width, active channel belt width, and active meander deposit dimensions) show a decrease in dimensions downstream, with a significant decrease in dimensions downstream of the avulsion point (where flow is diverted to the avulsed channel). Pre avulsion variables were also identified on the 2022 satellite imagery including pre avulsion channel belt width and abandoned meander deposit dimensions. Pre-avulsion channel belt width displays weak downstream trends and abandoned meander deposit dimensions display no downstream trends. Important differences in downstream trends were identified between active and abandoned meander deposit dimensions along the Taquari DFS. The active meander deposits are larger in size than the abandoned meander deposits upstream of the Caronal avulsion point and the abandoned meander deposits are larger than active meander deposits downstream of the avulsion point. The active meander deposits also show clear changes in size and shape downstream as they change from larger, more rounded deposits, to much smaller crescent-shaped deposits. The abandoned deposits however, display a range of shapes and sizes downstream and show no clear decrease in size, especially between medial and distal DFS zones. The decrease in active meander dimensions (active channel width, active channel belt width, and active meander deposit dimensions) is due to a decrease in discharge downstream as a result of typical DFS bifurcation processes in addition to the diversion of flow from the parent channel to the avulsed channel. Active meander deposit size and shape change downstream as sediment load, and therefore deposition, decrease as discharge decreases. The weak downstream trends displayed by the channel belt relate to confinement in the upper DFS where channel belt migration capacity is limited. The lack of downstream trends displayed by the abandoned meander deposits is due to the range of conditions under which these deposits were formed over time. This research has important implications for the understanding of avulsing rivers due to the significant decrease in width of the parent channel and the size of active deposit dimensions downstream, which influence the redistribution of water and sediment resources within modern DFS. In addition, this research creates an important database on the spatial variability of meander deposit dimensions on a modern DFS which can contribute to the understanding of sandstone-body reservoir dimensions which is important for resource exploration or hydrocarbon storage
Design and fabrication of biodegradable microfluidic platforms for enhanced tunnelling magnetoresistance sensor
Get PDFCancer remains a significant global health issue with its incidence and mortality rates increasing rapidly worldwide. Therefore, detecting cancer at an early stage can significantly increase survival rates. However, conventional diagnostic methods often depend on bulky, expensive equipment and require trained personnel, which limits their accessibility. This underscores the urgent need for simple, low-cost diagnostic devices that enable timely and effective early diagnosis. Microfluidics is a technology for controlling fluids at the microscale with high accuracy has emerged as a powerful potential instrument in biomedical and environmental processes, particularly when combined with cutting-edge sensing technologies and eco-friendly materials.
In this contribution, we investigated the design and fabrication of biodegradable microfluidic devices to improve the performance of tunnelling magnetoresistance (TMR) sensors by utilizing the biocompatibility of hydrogels, such as Polyethylene Glycol Diacrylate (PEGDA) and Gelatin Methacryloyl (GelMA), in conjunction with Polydimethylsiloxane (PDMS). Through photolithography and digital light processing three-dimensional (3D) bioprinting, we obtained high-resolution microchannel geometries, where PEGDA exhibited the best fidelity and printability.
In this study, channels with a width of 500 µm and a depth of 1 mm were fabricated successfully using a 25% PEGDA solution. Optimal fabrication was achieved after modifying the layer height settings of the CELLINK Lumen X DLP 3D printer from the initial 100 µm to 50 µm and subsequently to 20 µm. The platforms were validated using TMR sensors for detecting magnetic nanoparticles (MNPs) in the concentration range of 0 to 40 × 10³, showing a linear response with R² = 0.9771, indicating high sensitivity, reproducibility, real-time detection, and repeatable recovery of the baseline. These results underscore the potential of PEGDA- and PDMS-based biodegradable microfluidic devices for scalable biosensing applications. The integration of magnetic biosensing, hydrogelassisted microfabrication, and sustainable materials enables the development of nextgeneration diagnostic tools that are not only efficient and sensitive but also environmentally friendly and well-suited for point-of-care testing and home-based monitoring
Developing novel viral vectors to facilitate gene therapies for neuropathic pain
Get PDFNeuropathic pain (NeuP) is a chronic pain condition arising following injury or disease to the somatosensory system and affects 7-10% of the population worldwide. Despite its prevalence, currently available treatments for NeuP have limited efficacy and are often complicated by issues such as addiction. Spontaneous activity, a hallmark of NeuP, occurs in both injured and intact primary afferents and their relative contribution to pain remains a controversial subject, with the majority of evidence pointing towards an important role for injured afferents. Adeno associated viral (AAV) vector-based gene therapies are an attractive option for treating NeuP, however, their use is limited by immunogenicity and dorsal root ganglion (DRG) toxicity concerns. In this thesis, we designed viral vectors capable of delivering therapeutic transgenes and restricting their expression to injured, but not intact primary afferents. To achieve this, we initially developed a pipeline of in vitro and in vivo model systems to test the targeting of our vectors. Following this, we first investigated the capacity of the endogenous activating transcription factor 3 (ATF3) P1 promoter to target AAV gene expression. While the ATF3P1 AAV9 selectively limited transgene expression to injured sensory neurons in vitro, these results were not replicated in vivo. We next generated an epigenomic atlas of naïve DRG neurons using single nucleus Assay for Transposase Accessible Chromatin sequencing (snATAC-seq) and gained insight into the epigenomic signatures of injured and intact primary afferents. This data provides a resource for exploring the epigenomic mechanisms governing gene expression in the DRG and can be used to identify putative regulatory elements capable of targeting AAV gene expression to injured primary afferents. Finally, we trialled a microRNA (miRNA)-based approach, whereby miR-182 target sites were introduced into an AAV-PHP.S vector and successfully restricted expression to injured primary afferents in vivo
The influence of anthropogenic activities on cheetah space use and hunting success across a landscape of coexistence
Get PDFCheetahs (Acinonyx jubatus) occupy vast landscapes shaped by natural ecological processes and increasing anthropogenic pressures. Understanding how cheetahs navigate these environments is critical for their conservation, particularly in ecosystems like the Serengeti, where human activities and infrastructure continually expand. This synthesis integrates findings from three key studies conducted within the Serengeti ecosystem, investigating habitat selection, movement patterns, and hunting success in response to human and environmental factors. Using GPS collar data collected from ten cheetahs between 2022 and 2024, along with over 24,300 recorded locations and 110 hours of behavioural observations, we explore how cheetahs adapt to dynamic landscapes while balancing resource acquisition with risk avoidance.
Cheetahs demonstrated selective use of habitats influenced by both natural and anthropogenic factors. Generalized Linear Mixed Models (GLMMs) revealed that proximity to bomas, roads, and lodges, as well as environmental features like woody cover, slope, elevation, NDVI, and distance to rivers, significantly affected their habitat selection. During the wet season, cheetahs avoided areas near tourist lodges and roads, likely due to increased human activity, while in the dry season, they avoided occupied Maasai bomas, highlighting seasonal variations in space use. Environmental preferences showed the selection for areas with higher woody cover, flatter terrains, lower elevations, less green vegetation, and proximity to rivers, which may provide critical resources while avoiding other large carnivores.
Cheetahs’ movement patterns further underscored their adaptability and individual variation in how they responded to anthropogenic and environmental pressures at the local scale. Using Integrated Step Selection Functions (iSSFs), we assessed how proximity to human infrastructure influenced step lengths and turn angles of each collared cheetah, revealing complex responses. While bomas and roads generally deterred selection and changed the tortuosity of movement, some variability emerged, with cheetahs occasionally selecting areas near lodges during the dry season, potentially due to decreased human disturbance during this period of low tourism. Proximity to rivers was a consistent driver of movement across seasons, emphasizing the role of water availability in shaping cheetah movement decisions. These strategies illustrate how cheetahs navigate fragmented landscapes while mitigating risks from human activities.
Tourism, a cornerstone of Serengeti conservation, presents dual challenges and opportunities for wildlife. Our observational study of cheetah hunting behaviour revealed significant disruptions caused by tourist vehicles. Generalized Linear Mixed Models (GLMMs) indicated a strong negative relationship between vehicle presence and hunting decisions, with hunting probabilities dropping from 20% in vehicle-free conditions to nearly 0% in the presence of vehicles. Engine noise and the number of running engines further exacerbated these disturbances, prompting cheetahs to adopt passive behaviours such as lying down or sitting up, reminiscent of risk-avoidance strategies employed around dominant predators. These behavioural shifts have cascading demographic consequences, including reduced hunting opportunities and potential impacts on cub recruitment, threatening cheetah population viability.
This integrated understanding of cheetah space use, movement, and behaviour highlights critical areas for conservation focus. To mitigate the impacts of human activities, strategies should prioritize reducing human densities as well as activities that may directly and indirectly affect cheetahs’ survival, maintaining habitat connectivity, and managing tourism practices to minimize disturbances. Specific measures include establishing buffer zones around bomas and lodges, enforcing regulations on tourist vehicle numbers and engine noise near cheetahs, and implementing robust reporting systems for wildlife harassment. Collaborative approaches that engage local communities, park authorities, and stakeholders are essential to balancing conservation goals with human land-use needs.
Cheetahs exemplify the resilience required to navigate increasingly anthropogenic landscapes. However, their survival depends on proactive conservation strategies that address the dual pressures of habitat loss and human-wildlife interactions. By integrating insights from habitat selection, movement patterns, and hunting behaviour, this research provides actionable recommendations to safeguard cheetah populations in the Serengeti ecosystem especially those individuals that live along the park borderlands
A surrealist critique of ‘Brute’ reality: exploring reality, imagination, and dialectics in the French and Czech Surrealist philosophical framework
No full textAbstract not currently available
Data mining to constrain new physics in the top sector
Get PDFWe explore the Standard Model Effective Field Theory as a (mostly) modelagnostic route to obtaining data–driven limits on new physics. After briefly coveringsome foundational concepts, we introduce a modular and extensible framework thatenables data acquisition, analysis, and the fitting of EFT operators to experimentaldata from particle colliders. A global fit to top quark data is then performed, findinggood agreement with the Standard Model in most cases, and competitive resultscompared to a contemporaneous study. We then investigate, through the lens oftop partial compositeness and anomalous weak top quark couplings, the expectedlimiting factors for both HL–LHC and FCC–hh. We find the key factors in sensitivityin these scenarios to be theoretical uncertainties. We lastly explore the use of graph neural networks to boost sensitivity to EFT contributions, via what amounts to non–rectangular phase space cuts based on model classification, finding significant improvements to be possible in both individual and profiled constraints
Understanding the role of Dead box helicase 1 (DDX1) and its co-factors in alphavirus infection
Get PDFThe tRNA ligase complex (tRNA LC) is essential in tRNA maturation, stress response pathways and viral regulation, among others. It comprises proteins with distinct roles, including a non-canonical GMP-driven RNA ligase, RTCB, a cap-binding protein CGI99, and an ATP-dependent RNA helicase DDX1. In Sindbis virus (SINV), the tRNA-LC relocalises to viral replication organelles and interacts directly with viral RNA (vRNA). However, the functional role of the tRNA-LC in SINV infection remained unclear. This thesis characterises tRNA-LC interaction dynamics and elucidates its antiviral mechanism during SINV infection. Co-precipitation and crosslinking mass spectrometry (XL-MS) demonstrated robust inter-protein interactions, with DDX1, RTCB, and CGI99 forming the core of a tightly coordinated complex. CGI99 emerged as a central component, corroborated by Alphafold3 (AF3) modelling and complex destabilisation following a siRNA-mediated knockdown. Novel interactions, such as those with RPL11 and MYH9, suggest broader functional implications. The tRNA-LC displayed potent antiviral activity, as depletion of DDX1 and CGI99 significantly increased viral protein production and downregulated over 11,000 host genes during SINV infection. These findings indicate that tRNA-LC plays a central role in restricting viral lifecycle, and in its absence, the cellular microenvironment is more favourable to host viral infection. To identify the antiviral mechanism exerted by the tRNA-LC, I assessed how its RNA and protein interaction landscapes were altered during infection. The interaction landscape of the tRNA-LC analysed via iCLIP2 and protein-protein interaction analysis revealed a transition from cellular mRNA to vRNA binding during infection, primarily targeting the 5’ UTR and the start of the coding sequence. Enhanced interactions with ribosomal factors suggested involvement in translation regulation. Using a SINV replicon system, DDX1 was identified as regulating both viral replication and translation. This study proposes that the tRNA-LC inhibits vRNA processes by blocking essential viral factors such as replicase or translation components accessing the vRNA, offering new insights into its antiviral mechanisms and potential applications against positive-strand RNA viruses
Investigating radiation-driven invasion and metastasis in pancreatic cancer
No full textAbstract not currently available
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