143174 research outputs found
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Green light vat‐photopolymerisation for 3D printing hydrogels with complex lattice structures
No full textMoving beyond UV curing systems opens new potential application spacessuch as biological, portable printing solutions, as well as innovative chemistriesand material properties. A novel visible light printer is proposed for the first timeusing green Digital Light Processing (gDLP) at a wavelength of 514 nm. GreenLED lights are integrated into a commercial desktop DLP printer to 3D printhydrogels with complex designs at high resolution. A workflow process is pre-sented to develop and optimize formulations for gDLP, resulting in two novel in-house photoresin formulations made specifically for green light printing. Theseformulations comprise PEGDA 700 with and without acrylamide, using a type IIphotoinitiating system of Eosin Y, triethylamine, and N-vinylpyrrolidone. Thephotoresins are optimized to achieve highly vascularized lattice prints by mod-ulating layer light exposure, chemical components, and photoinitiator concen-trations. The gDLP successfully printed hydrogels with a layer height of 50 mand feature dimensions as small as 0.3 mm by adjusting light duration per layer.3D printed hydrogels using both formulations are tested for varying designcomplexity, including ISO/ASTM standards, and evaluated with optical imag-ing, SEM, and mechanical testing. This study highlights gDLP technology’s po-tential for diverse applications in tissue engineering and sustainable materials
Investigating elastic properties with full-waveform inversion at the hikurangi margin
No full textFull-waveform inversion (FWI) is an inversion technique that generates high-resolution physical property models of the subsurface. The NZ3D dataset was acquired to perform FWI and generate P-wave velocity models of the Hikurangi margin. In this project, I develop a reliable workflow to apply FWI on this dataset. I perform a 2D FWI that images the accretionary wedge as well as the d´ecollement and a 3D inversion which focusses on a near-surface area within the accretionary wedge. This area is characterized by a thrust ridge with a relatively strong bottom-simulating reflector (BSR). In order to investigate this BSR, I apply a newly developed method that allows the use of acoustic FWI to analyse the amplitude-versus-offset (AVO) effect in the seismic data and, thereby, resolve the elastic parameters and investigate the fluid distribution along the BSR. While the applicability of this method has been proven for synthetic data, this study is the first to apply it to field data. Additionally, I perform rock-physics modelling for the study area which allows me to relate the P-wave velocities in the FWI model to rock properties providing gas hydrate and free gas saturation estimates for the BSR and a quality control for the application of the FWI AVO method. I jointly interpret the results from the FWI, the FWI AVO analysis and the rock-physics modelling to identify the cause of the investigated BSR. The BSR is characterised by a higher gas saturation within the basin which decreases towards the ridge and vice-versa for the gas hydrate saturation. The gas hydrate was probably generated during the process of hydrate recycling and sourced by free gas flow from below the BSR into the gas hydrate stability zone along permeable structures.Open Acces
An in‐depth study of the solid electrolyte interphase compositional evolution in sodium‐Ion batteries: unravelling the effects of a Na metal counter electrode on the SEI
No full textA comprehensive understanding of the solid electrolyte interphase (SEI) is crucial for ensuring long-term battery stability. This is particularly pertinent in sodium-ion batteries (NIBs), where the SEI remains poorly understood, and investigations are typically undertaken in half-cell configurations with sodium metal as the counter electrode. Na metal is known to be highly reactive with common carbonate-based electrolytes; nevertheless, its effects on SEI formation at the working electrode are largely unexplored. This work investigates the evolution of the SEI in NIBs during cycling, with an emphasis on the consequences of using a sodium metal counter electrode. Advanced analytical techniques, including hard X-ray photoelectron spectroscopy (HAXPES) and time-of-flight secondary ion mass spectrometry (ToF-SIMS), are used to obtain depth-resolved insights into the chemical composition and structural changes of the SEI on hard carbon anodes during cycling. The findings demonstrate that the cell configuration has a significant impact on SEI evolution and, by extension, battery performance. These findings suggest that full-cell studies are necessary to better simulate practical operating conditions, challenging traditional half-cell experiments
Approximation, control and observation of complex dynamical systems
No full textThe present work contributes to the topics of approximation, control, and observation of complex dynamical systems. The thesis consists of three parts. The first part of the thesis considers the approximation of large-scale systems. First, the data-driven model order reduction (MOR) by moment-matching is considered, with a focus on multiple-input multiple-output (MIMO) systems. Then, the developed method is validated on a combined system of a 200-turbine wind farm interconnected to the IEEE 14-bus system. The second part of the thesis deals with three classes of state-feedback control problems for stochastic nonlinear systems. Exploiting a dynamic extension, approximate solutions are provided for optimal control problems and min-max zero-sum games while exact solutions are given for the H-infinity control problem. The level of approximation can be exactly quantified in terms of an additional cost, which gives the distance from the optimal solution. Finally, the observation of stochastic linear systems is presented in the last part of the thesis. An a posteriori method is considered to approximate the variations of the Brownian motion. Based on this approximation, a hybrid observer is constructed, with the property that the estimation error converges to zero asymptotically in probability as the sampling period tends to zero.Open Acces
Geometry-aware sound source localization using neural networks
No full textSound Source Localization (SSL) is the topic within acoustic signal processing which studies methods for the estimation of the position of one or more active sound sources in space, such as human talkers, using signals captured by one or more microphone arrays. It has many applications, including robot orientation, speech enhancement and diarization.
Although signal processing-based algorithms have been the standard choice for SSL over past decades, deep neural networks have recently achieved state-of-the-art performance for this task.
A drawback of most deep learning-based SSL methods consists of requiring the training and testing microphone and room geometry to be matched, restricting practical applications of available models. This is particularly relevant when using Distributed Microphone Arrays (DMAs), whose positions are usually set arbitrarily and may change with time. Flexibility to microphone geometry is also desirable for companies maintaining multiple types of microphone arrays in their line of products, and smaller companies or practicioners who wish to apply freely available pre-trained, off-the-shelf SSL models to their applications.
The main contributions of this thesis are the creation of a novel class of neural network models for the tasks of Positional Sound Source Localization (PSSL) and Direction-of-Arrival (DOA) estimation, named Neural-SRP. The method combines concepts from graph neural networks as well as from the classical Steered Response Power (SRP) localization method. Unlike current state of the art networks for SSL, the Neural-SRP method is able
to function on microphone arrays and rooms of arbitrary geometry, while maintaining or improving localization performance.Open Acces
Rifampicin exposure in tuberculosis patients with comorbidities in sub-Saharan Africa: prioritising populations for treatment—a systematic review and meta-analysis
No full textBackground and Objectives
Emerging evidence suggests that comorbidities like human immunodeficiency virus (HIV) infection, diabetes mellitus (DM), and malnutrition in tuberculosis (TB) patients can alter drug concentrations, thereby affecting the treatment outcomes. For these populations, personalised strategies such as therapeutic drug monitoring (TDM) may be essential. We investigated the variations of drug levels within comorbid populations and analysed the differences in patterns observed between sub-Saharan Africa (SSA) and non-SSA regions.
Methods
We performed a systematic review and meta-analysis of rifampicin drug pharmacokinetics (PK) through searches of major databases from 1980 to December 2023. A random-effects meta-analysis model using R-studio version 4.3.2 was conducted to estimate pooled serum rifampicin exposure (area under the concentration-time curve [AUC], and peak maximum concentration [Cmax]) between patients with TB-HIV infection, and TB-DM.
Results
From 3300 articles screened, 24 studies met inclusion criteria, contributing 33 comorbidity subgroups for meta-analysis. In SSA, 14 subgroups assessed rifampicin PK in TB-HIV, 1 in TB-DM, and none in TB-malnutrition. The pooled mean Cmax was below the recommended range (8–24 mg/L) for all subgroups. For TB-HIV, the pooled Cmax was 5.59 mg/L, 95% CI (4.59–6.59), I2 = 97% for SSA populations and 5.59 mg/L, 95% CI (3.65; 6.59) for non-SSA populations. The Cmax for TB-DM in SSA (9.60 ± 4.4 mg/L) exceeded non-SSA (4.27 mg/L, 95% CI [2.77–5.76]). The lowest AUC was in TB-HIV (SSA, 29.09 mg/L h, 95% CI [21.06; 37.13, I2 = 91%]). High variability and heterogeneity (I2 >90%) were observed, with most studies (20/23) showing low bias.
Conclusion
Our results emphasise the need for individualised dosing and targeted TDM implementation among TB-HIV and TB-DM populations on rifampicin in SSA. Although all populations exhibited low Cmax levels, TB-HIV populations may be prioritised as AUC levels were lowest. In clinical settings in SSA, Cmax-based TDM is more practical, but AUC can be used in treatment where feasible
An engineering biology approach and infrastructure for automating workflow in a biofoundry
No full textEngineering biology applies engineering principles to the design and construction of biological systems. Since its inception twenty-five years ago, approaches to engineering biology have transitioned from traditional wet lab manual methods, to using individual automated devices, to a complete integration of workflows in fully automated laboratories called Biofoundries.
Engineering biology applications require the navigation of large design spaces and the control of assays. To explore large design spaces in reasonable time and cost statistical methods need to be employed. The solution is automation, which provides a throughput high enough to enable the repetition of large numbers of assays. Automation provides higher control and reduces the influence of human operators. High throughput automation generates large measurement datasets which need to be dealt with computational automation.
The work presented in this thesis took place in the London Biofoundry - SynbiCITE. The contribution of the work presented here is a framework and a software system for supporting infrastructure in a Biofoundry. To study the problems that arise from automating an engineering biology application, a case study based on Lycopene was undertaken.
The lycopene application was chosen because it is a good metabolic engineering case study, based on a model pathway with a large design space. The goal of the case study was the optimisation of bioproduction of a metabolite of high bioeconomic interest, lycopene. Through the development of the lycopene case study, lessons were learned: the necessity to design a scoping study and the necessity to care for errors induced by automated methods.
The work presented in the thesis utilises lessons learned from the case-study and presents an infrastructure/framework to support automation orchestration in a Biofoundry. Our framework was validated on data collected with the lycopene application.Open Acces
Cardiac resynchronisation by conduction system pacing: patient selection by high-precision invasive and non-invasive phenotyping.
No full textConduction system pacing (CSP) is a physiological approach to cardiac resynchronization (CRT) where cardiac electrical activation can be restored to normal. The standard form of CRT is Biventricular pacing (BVP), this was introduced in 1994 by Cazeau et al who demonstrated haemodynamic benefit. Multiple large randomized controlled trials have shown mortality and morbidity benefit with BVP. However, some BVP receivers did not benefit, and overall mortality and morbidity rates remained high. Conduction system pacing emerged as an alternative option because it delivers a more physiological form of CRT. His bundle pacing (HBP) was pioneered in 2000 by Deshmukh et al in patients with advanced heart failure. Left bundle branch area pacing (LBBAP) emerged as an alternative modality in 2017. Early reports suggested that pacing parameters were better than HBP and it has can correct more distal conduction abnormalities. Although HBP and LBBAP are both safe and feasible modalities for CRT, it is not known which one is better. This thesis explores the effectiveness of HBP and LBBAP to deliver CRT. In Chapter 3, a within-patient comparison of the two modalities, and compared to BVP is demonstrated. In Chapter 4, multiple non-invasive investigations were performed before CSP. The aim was to identify patient characteristics that predict successful CSP. In Chapter 5, I investigated the impact of septal scar on the success of LBBAP. This is crucial for procedural planning and tool selection. In Chapter 6, I explore variable right ventricular activation patterns associated with different programming of devices with LBBAP lead. I investigate the impact of anodal stimulation on ventricular activation times. This thesis elucidates the effectiveness of two novel CRT modalities targeting the conduction system and compares them to BVP. It provides a framework for patient selection for conduction system pacing, which can be utilized in future clinical trials.Open Acces
Connective tissue disorder and high risk pregnancy: a case series with personalised external aortic root support (PEARS)
No full textAortopathy including Marfan (MFS) and Loeys-Dietz syndrome (LDS) poses a high risk of aortic dissection, particularly during pregnancy and the puerperium. Current preventive measures of aortic root dilatation include medical therapy and prophylactic aortic root replacement. The Personalised External Aortic Root Support (PEARS) operation has been developed as an alternative surgical strategy to prevent aortic root dilatation and is now an established procedure with a good prognosis. However, outcomes in pregnant women are unknown. We present case series of nine successful pregnancies in seven women with aortopathy (6 MFS and 1 LDS) who underwent PEARS procedure prior to conception. At a mean follow-up of 4.3 years after delivery, there was no type A or B aortic dissections. Aortic dimensions remained stable, and no hypertensive disorders were observed. Although this is a small retrospective study, PEARS procedure may be a viable pre-conception surgical strategy for women with aortopathy, as an alternative to conventional aortic root surgery. Further studies are needed to conclude that PEARS could be a non-inferior or superior alternative to conventional aortic root surgery in these patients
What are community perspectives and experiences around GLP-1 receptor agonist medications for weight loss? A cross-sectional study in the UK
No full textIntroduction Obesity is a critical public health challenge globally. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have demonstrated significant efficacy in weight loss; however, their adoption is influenced by various individual and societal factors. This study sought to examine awareness, motivations and barriers to adoption of GLP-1RAs in the UK, with a focus on demographic differences.
Methods A cross-sectional survey of 1297 UK adults was conducted using an electronic questionnaire distributed via social media, online platforms and personal networks. The survey assessed demographic characteristics, awareness, perceptions and use of GLP-1RAs. Data were analysed using χ2 and Kruskal–Wallis tests. The primary analysis method was ordinal logistic regression, with multinomial logistic regression used to estimate the relative risk ratio (RRR) if the proportional odds assumption was violated. A p-value<0.05 was considered significant.
Results Significantly higher awareness of GLP-1RAs was observed among those attempting weight loss in the past year (85.7% vs 14.3%, p<0.001). Women were more likely to report both awareness (87.2% vs 68.2%, p<0.001) and excellent understanding (20.0% vs 7.5%, p<0.001). Main information sources included news (60.1%) and social media (50.3%). Only 9.0% first learnt about GLP-1RAs from healthcare providers. Past and current users were less likely than non-users to express scepticism about safety and efficacy and 6.91 times more likely to strongly disagree (compared with being neutral) that ‘risks outweigh the benefits’ (RRR, 6.91; 95% CI, 4.32 to 11.05; p<0.001) and 7.33 times more likely to strongly disagree (relative to being neutral) that ‘there is not enough evidence to suggest GLP-1RAs are safe’ (RRR, 7.33; 95% CI, 4.05 to 13.27; p<0.001). 91.0% of current or past users indicated they would recommend GLP-1RAs to a friend struggling with weight management.
Conclusion Concerns about safety, cost and potential side effects remain significant barriers to GLP-1RA adoption. Current or past users strongly disagree with statements of scepticism; however, scepticism among non-users highlights the need for improved public education around safety and efficacy