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Investigating the role of different dietary patterns on gut metabolites
No full textThis thesis investigates the interplay between dietary patterns and gut metabolites, focusing on short-chain fatty acids (SCFAs) and bile acids (BAs), key contributors to gut metabolism. It addresses the need to move beyond reductionist, nutrient-specific approaches by examining how whole dietary patterns shape metabolic outcomes. Using advanced analytical techniques, including novel Gas Chromatography-Mass Spectrometry (GC-MS) and Liquid Chromatography-Mass Spectrometry (LC-MS), this work evaluates gut-related metabolites across contrasting diets.
Two primary studies frame this research. The first examines SCFA and BA concentrations in free-living vegans and omnivores within a cross-sectional cohort. Significant metabolic differences emerged between these groups. Vegans showed elevated SCFA concentrations in biofluids, reflecting their high-fibre diets, whereas omnivores exhibited increased secondary bile acids in faecal samples, likely linked to higher fat intake. These results highlight the distinct effects of plant-based versus omnivorous dietary patterns on gut-derived metabolites and their potential implications for health.
The second study investigates the acute metabolic effects of contrasting dietary patterns in a randomised, controlled, crossover trial. By monitoring SCFA and BA concentrations following healthy and unhealthy diets, this study captures temporal fluctuations in metabolite profiles. SCFA levels varied with dietary intake and displayed notable inter- and intra-individual variability. For BAs, temporal variation appeared stronger than dietary effects. Integrating metabolomic and dietary data, this work emphasises the dynamic and personalised nature of gut metabolite responses among individuals consuming the same diet.
Overall, this thesis advances understanding of the complex interactions between diet, host metabolism, and the microbiota. Recognising the role of metabolite variability is essential for interpreting metabolic pathways and developing tailored dietary recommendations. By elucidating how dietary patterns shape gut metabolites under real-life and controlled conditions, this research contributes to future applications in precision nutrition and supports the development of metabolite-informed dietary strategies.Open Acces
Do markets deliver? Competition and Choice in European healthcare markets
No full textIn the last two decades European policy makers have sought to increase the use of market mechanisms in the delivery of healthcare. These reforms introduce competition and choice into previously heavily constrained environments. This leads to a set of interesting economic issues that have been addressed in a range of papers, both theoretical and empirical. This paper examines whether this popular reform model has resulted in improvements in outcomes for patients and/or taxpayers. It synthesises the existing economic analyses, highlights what is known and what is not, and signals potential next steps for economic research
Obesity, metabolic health status, and adverse outcomes in men and women
No full textBackground
Metabolically healthy obesity account for approximately one-third of individuals with obesity and could affect up to 300million individuals worldwide. Whether this is a truly benign cardiometabolic phenotype as the name suggests is incompletely defined, leading to uncertainty regarding the optimal risk stratification and management strategies for these individuals.
Objectives
To assess the sex-specific independent and joint associations of obesity and metabolic health status on cardiometabolic outcomes and death.
Methods
A prospective cohort study of UK Biobank participants free from cardiovascular diseases and not underweight. Participants were divided by BMI into normal, overweight or obese, and the presence or absence of ≥1metabolic abnormality (hypertension, diabetes or dyslipidaemia). Exposures were assessed at baseline(2006-2010), with outcomes ascertained over a median follow-up of 12.9 years(IQR 12.6-13.3). Sex-specific outcomes were fatal or non-fatal atherosclerotic cardiovascular disease(ASCVD; a composite of coronary heart disease, ischaemic stroke, and peripheral artery disease), heart failure(HF), metabolic dysfunction-associated steatotic liver disease(MASLD), end-stage renal disease(ESRD) and all-cause mortality. Multivariable-adjusted cox regression models were used to estimate hazard ratio (HR) and 95%CI.
Results
Among 157,159 participants (mean age 56.5years [SD 8.2]; 55.6% women), 24.2% were obese and 68.2% had ≥1 metabolic abnormality. Compared to normal BMI and no metabolic abnormality (reference group), obesity was associated with increased risk of ASCVD(HR 1.46, 95%CI 1.24-1.73), HF(1.63,1.14-2.32), MASLD(2.37,1.22-4.61), all-cause mortality(1.36,1.10-1.69) but not ESRD in men without metabolic abnormalities, which increased when any metabolic abnormality was present: ASCVD(2.21,2.03-2.41), HF(2.91,2.41-3.50), MASLD(6.84,4.60-10.18), ESRD(5.42,2.94-10.02), and all-cause mortality(1.62,1.45-1.81). Corresponding risk from obesity in women without metabolic abnormalities were: ASCVD(1.34,1.14-1.58), HF(1.69,1.21-2.37), MASLD(4.44,3.00-6.59), and all-cause mortality(1.27,1.05-1.52) but not ESRD, which increased when metabolic abnormalities were present: ASCVD(2.51,2.30-2.74), HF(3.67,3.04-4.43), MASLD(8.17,6.13-10.89), ESRD(7.96,4.00-15.85) and all-cause mortality(1.67,1.51-1.85). Adverse outcomes increased with severity of obesity, the presence of central obesity, and with increasing numbers of metabolic abnormalities, with an effect modification by sex suggesting more harm from obesity, central obesity and metabolic abnormalities in women.
Conclusions
Obesity without metabolic abnormalities is not benign and associated with multiple adverse cardiometabolic outcomes, further exacerbated when metabolic abnormalities occur. As 300million individuals may be considered metabolically healthy but obese, future studies should explore whether preventing or reversing obesity prior to the appearance of significant metabolic abnormalities results in improved health outcomes
Hybrid frequency-phase-shift modulation with natural synchronous rectification for CLLC converters
No full textSynchronous rectification (SR) is an effective method
to improve the efficiency of the CLLC resonant converter. However, existing SR methods typically rely on calculating specific SR angles based on pulse frequency modulation (PFM) or phase shift modulation (PSM), which do not overcome the intrinsic efficiency drawbacks of these modulations. To address this, this paper proposes a hybrid modulation that integrates switching frequency and phase shift to achieve natural SR and modulation optimization simultaneously. Rather than SR angle calculation, the proposed modulation combines the two control variables to synchronize the operation of the primary side switches and secondary side rectifiers (diodes or SR switches). This alignment enables natural SR by gating the secondary switches concurrently with the primary switches. Furthermore, the proposed modulation reduces the RMS value of inductor current and extends the ZVS range compared to PSM. In contrast to PFM, the proposed
method operates at a lower switching frequency, thereby reducing switching losses. The modulation is achieved by a closed-loop control for switching frequency and a precomputed fitting curve for phase shift. A series of experimental results have verified the effectiveness of the proposed modulation
Renewal theory for Brownian motion with stochastically gated targets
No full textThere are a wide range of first passage time (FPT) problems in the physical and life sciences that
can be modelled in terms of a Brownian particle binding to a reactive target surface and initiating a downstream event (absorption). However, prior to absorption, the particle may undergo several rounds of surface attachment (adsorption), detachment (desorption) and diffusion. That is, the surface is effectively ‘sticky’. Alternatively, the surface may be stochastically gated so that absorption can only occur when the gate is open. In both cases one can view each attachment to
the surface as a renewal event. In this paper we develop a renewal theory for stochastically gated target problems along analogous lines to previous work on sticky targets. We proceed by constructing a first renewal equation that relates the joint probability density for particle position and the state of a gate to the probability density and FPT density for a totally absorbing (non-gated) boundary. This essentially decomposes sample paths into an alternating sequence of bulk diffusion and instantaneous adsorption/desorption events, which is terminated when adsorption coincides with an open gate. In order to ensure that diffusion restarts in a state that avoids immediate re-adsorption, we assume that whenever the particle reaches a closed boundary it is instantan
eously shifted a distance ϵ from the boundary (desorption-induced resetting). We explicitly solve
the renewal equation in the one-dimensional case and show how the solution to the original gated FPT problem is recovered in the limit ϵ → 0. We then calculate the MFPT for absorption (assuming it exists) and determine its dependence on ϵ and the switching rate of the gate. We also show how spectral methods can be used to solve the renewal equation in higher spatial dimensions. We thus establish renewal theory as a general mathematical framework for modelling both sticky and
stochastically gated targets
Advances in cryo-EM that have shaped mechanistic models of membrane attack complex assembly and regulation
No full textThe complement system is a blood-based immune network that plays a crucial role in fighting infection and maintaining immune homeostasis. The membrane attack
complex (MAC) is a pore assembled from complement proteins that creates holes in cells when the immune system is activated. Over the last 10 years, advances in cryo electron microscopy (cryo-EM) have enabled key molecular insights into how MAC assembles, remodels membranes, and is regulated. These new tools revealed the inherent flexibility of complement complexes. By adapting computational approaches that disentangle diverse conformations, these studies have provided detailed mechanisms for MAC activity that could underpin novel complement-targeted therapeutics. Now accelerated by AI-driven image analysis and advances in structural cell biology, the next revolution in cryo-EM o ers new opportunities to understand the cellular consequences of immune activation
Microplastics and respiratory health
No full textPlastics are ubiquitous in the 21st century, as products and as waste. From production through use and to recycling or disposal, plastics release, via physical, chemical and/or
biological degradation processes, highly diverse and ill-defined particles into air, soil and water. Major sources of plastic debris include everyday items such as clothes made of synthetic materials, tires, packaging, consumer products, and paint. Owing to their longevity in the environment, plastic particles - encompassing macro- (>5mm), micro- (1µm-5mm) and nano- (<1µm) plastics - accumulate in indoor and outdoor environments promoting a substantial research effort into their ecological impacts and risks to human health. Given (a) that inhalation represents an important route of exposure, (b) the links between respiratory disease and high doses of inhaled plastics amongst individuals exposed in industrial settings
and (c) the vast literature showing that inhaled particles of many types cause lung injury, the impact of microplastics on respiratory health and disease is being actively investigated
Autocuidado é aposta de centro de pesquisa do Imperial College de Londres pioneiro no estudo do tema [Self-care is the focus of a pioneering research centre at Imperial College London in the study of the subject]
No full textFeature in Futuro da Saúde (Brazillian) discussing the role of Imperial College London Self-Care Academic Research Unit (SCARU) in advancing slef-care research & gobal self-care policy
Public involvement Insight Report - Proposed clinical trial to understand how Tirzepatide affects bone health in people living with obesity
No full textPublic involvement insights about a proposed trial for GLP1 medicatio
On-chip III-V semiconductor network lasers for neuromorphic computing
No full textModern Artificial Intelligence workloads are placing a growing amount of strain on digital hardware, increasing costs and energy demands. The field of neuromorphic computing seeks to help alleviate this problem through physical platforms that could be used as accelerators for machine learning tasks. Network lasers are a promising but unexplored platform for this application -- they support a high number of interacting lasing modes through multiple scattering between defined waveguiding paths, and their complexity, non-linearity, sensitivity, and compact size address several challenges facing the field of photonic neuromorphic computing. To enable their use as a computing platform, we need to move them from the current dye-doped electrospun polymer platform to a lithography-defined semiconductor process, which allows for fully designable lasers, and high resiliency to degradation under pumping.
To implement this vision, I first explore the etching of III-V semiconductor layers to create photonic nanodevices. Parameter optimisation allows us to produce high quality structures from InP, our main material of interest, as well as other epitaxial platforms like InGaAs quantum wells. Next, I study the lasing from etched microdisk devices, presenting multiple ways in which lasing properties can be used to inform fabrication choices. With fabrication and lasing performance validated, I present experimental measurements from etched semiconductor network lasers, investigating the physics behind the lasing modes and their coupling. Finally, I show the application of network lasers to neuromorphic computing, first through edge detection, which matches the mode competition dynamics of the laser, and then for image classification, also combining the two schemes to form a photonic convolutional neural network. We obtain high classification accuracies on tasks including MNIST, Fashion MNIST, and BreaKHis 400X, especially in the few-shot regime, and explore the likely physical basis of the neuromorphic performance