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Understanding the role of obesity-mediated white adipose tissue and liver crosstalk
No full textObesity drives white adipose tissue (WAT) changes which can lead to its dysregulation and insulin resistance. The obesity-mediated loss of WAT homeostasis can trigger liver steatosis through dysregulated lipid pathways such as those related to polyunsaturated fatty acid (PUFA)-derived oxylipins. Cross-tissue dynamics of the WAT and liver in progressive obesity remains elusive and the exact relationship between oxylipins, metabolic syndrome and metabolic dysfunction-associated liver disease (MASLD) is ill-defined. My aim was to understand the transition from adaptive to maladaptive WAT homeostasis in humans and its repercussion on liver homeostasis. Using oxylipins as potential messengers between WAT and the liver, my objective was to clarify their role in obesity-related T2DM/MASLD.
Methods: I phenotyped the omental WAT (oWAT) of N=88 patients with obesity undergoing bariatric surgery and n=9 control patients and correlated the obesity-related phenotype with MASLD progression in N=41 paired liver biopsy, plasma and oWAT samples. I integrated these finding with multi-tissue profiling (liver, oWAT and plasma) of PUFA-derived oxylipins during progression toward insulin resistance and MASH. Potential drug-effects were investigated through analysis of Metformin-treated fat explants ex vivo.
Findings: Obesity-mediated adipocyte hypertrophy is associated with down-regulation of PPAR and CEBP independently of T2DM, increased macrophage infiltration and reduction in Collagen type I and VI. Obese oWAT explants treated with Metformin demonstrated increased adipogenic markers (PPARY, FABP4, CD36). Multi-tissue oxylipin profiling revealed a generalized down-regulation of cytochrome P450 (CYP)-derived diols during obesity conserved between the oWAT and plasma. Notably, epoxide:diol ratio, indicative of soluble epoxide hydrolyse (sEH) activity, increased with hepatic steatosis and T2DM.
Interpretation: These results reveal a distinct oWAT phenotype occurring with obesity and metabolic syndrome and propose Metformin is adipogenic. The oxylipin signature in obesity suggests a possible role of fatty acid diols during metabolic syndrome and a dampened sEH activity in WAT and liver in T2DM/MASLD.Open Acces
The impact of nitrate dosing and semi-conductive media on anaerobic fluidised-bed treatment of low-strength wastewater
No full textThis thesis describes the performance of two anaerobic fluidised-bed bioreactors (AFBRs) operated over 290 days and the microbial communities within. Both reactors utilised 7-channel plastic beads as the fluidised media, however, in one reactor, the media had a semi-conductive polyaniline coating to stimulate direct interspecies electron transfer (DIET). The synthetic low-strength wastewater fed into the reactors also contained a low dose of nitrate, stimulating denitrification, as well as both nitric oxide dismutation and dissimilatory nitrate reduction to ammonia (DNRA).
Although the performance data showed no significant difference to the methane production or yield between the two AFBRs, metagenomics analysis showed that the polyaniline coating did favour electroactive microbes. Furthermore, by the late stages of operation, a constant low presence of oxygen stimulated a high relative abundance of oxygen-tolerant methanogens. This demonstrates that polyaniline is successful at stimulating DIET, however, the performance of methanogenesis may have been impacted by the presence of nitrate.
The presence of oxygen in the biogases and the increased concentration of ammonia in the effluents confirmed the activation of nitric oxide dismutation and DNRA. Furthermore, genes for DNRA were detected and sequence similarity searches found genes that had some similarity to nitric oxide dismutase genes. Mass balances calculations showed that the polyaniline-containing AFBR had a higher rates of nitrous oxide production. This implies that DIET favoured conventional denitrification, albeit incomplete, over nitric oxide dismutation or DNRA.
This experiment is the first to explore any relationship between DIET and nitric oxide dismutation, ultimately finding no evidence of linkage between the two. This is likely due to nitric oxide dismutation being an electron neutral reaction, and therefore DIET does not confer any advantage. The establishment of nitric oxide dismutation in an anaerobic wastewater treatment reactor shows great potential for reducing nitrous oxide emissions if the process can be scaled.Open Acces
Quantifying key economic uncertainties in the cost of trading green hydrogen
No full textIn a fully decarbonized global energy system, hydrogen is likely to be one of few energy vectors that can facilitate long-distance export of renewable energy. However, because of divergent literature findings, consensus is yet to be reached on the total supply chain costs of shipping hydrogen either as a cryogenic liquid or ammonia. To this end, this article presents a detailed process systems-based economic analysis of a typical hydrogen value chain in 2050, employing the method of elementary effects to quantify the effect of uncertainties. With expected landed costs for liquid hydrogen of 3.30 kg−1(H2), the importance of uncertainty quantification is demonstrated, given that specific parametric combinations can yield landed costs below 4.70 kg−1(H2), these results demonstrate the stark difference between the aspirations of decarbonization policy (with some countries aiming for prices below $1 kg−1 by 2050) and the present techno-economic reality
Microscopic mechanism of cellulose nanofibers modified cemented gangue backfill materials
No full textReinforcing the performances of cemented backfill materials to recycle gangue and tailings is crucial for the sustainable development of mineral resources and mining waste management. However, under practical constraints of low cost, high waste ratio, low carbon emission, and low binder consumption, solidifying upcycles of mining wastes with toxicity, porosity, and mollification to cemented backfill materials with superior properties are inherently contradictory and challenging. This study reported a waste-to-wealth pathway that improves cemented gangue backfill materials by cellulose nanofibers to recycle mining wastes and partially replace cement. Mechanical compression, X-ray diffraction, thermogravimetry, mercury intrusion porosimetry, scanning electron microscopy tests, fractal quantitative analyses of microstructures, and molecular dynamics simulations were carried out to reveal the action mechanism of TEMPO-modified cellulose nanofibers on cemented gangue backfill materials. The difference in the contribution of TEMPO-modified cellulose nanofibers and mechanical cellulose nanofibers to the strengths of cemented gangue backfill materials was analyzed. The results show a series of microscopic improvements of cellulose nanofibers on cemented gangue backfill materials, including regulating cemented gel polymerization, increasing hydration nucleation, inhibiting carbonization, densifying pore structure, enhancing Ca-O connections and H bonds, and preventing C-S–H fracture along interlayer water. Excessive cellulose nanofibers are also found to be harmful to this composite mainly by delaying hydration crystallization and increasing pores by entrapping air, while it still exhibits improvements in deformation resistance and energy absorption despite strength deterioration. The strength and energy absorption reinforcements of this cemented hybrid materials induced by cellulose nanofibers with optimal dosage can reach up to 30 ~ 50%
Identification of physiological adverse events using continuous vital signs monitoring during paediatric critical care transport: a novel data-driven approach
No full textInterhospital transport of critically unwell children exacerbates physiological stress, increasing the risk of deterioration during transport. Due to the nature of illness and interventions occurring in this cohort, defining “normal” vital sign ranges is impossible, which can make identifying deterioration events difficult. A novel data-driven approach was developed to identify adverse respiratory and cardiovascular events in critically ill children during interhospital transport. In this retrospective cohort study of 1,519 transports (July 2016 to May 2021), vital signs were recorded at one-second intervals and then analysed using an adaptation of Bollinger Bands, a technique borrowed from financial market analysis. This method dynamically established each patient’s stable ranges for heart rate, blood pressure, oxygen saturation, and other respiratory parameters, and flagged adverse events when multiple parameters simultaneously fell outside their expected ranges. Adverse respiratory events were identified when oxygen saturation deviated below a dynamically defined threshold alongside at least one additional respiratory parameter. Cardiovascular events were defined by concurrent deviations in blood pressure and heart rate. Overall, 15.6 percent of transports had one or more adverse respiratory events, and 21.5 percent had at least one adverse cardiovascular event. To validate these labels, the number of adverse events and the cumulative duration of vital sign instability during transport were compared against clinical markers of deterioration. Each additional respiratory event was associated with increased odds of receiving respiratory support during transport and higher 30-day mortality, while each additional cardiovascular event was associated with increased odds of receiving vasoactive support during transport. Our method detects respiratory and cardiovascular adverse events during transport. The approach is readily adaptable to other high-resolution intensive care datasets, for both retrospective labelling as well as automated, real-time identification of adverse events in the clinical setting, offering a foundation for improved monitoring and early intervention in critically ill patients
Strain engineering of dealloyed nanoporous cu for electrochemical CO(2) reduction
No full textThe electrochemical CO2 and CO reduction reaction (CO(2)RR) enables the recycling of greenhouse gases into valuable chemicals and fuels using renewable electricity. Among catalysts, Cu is unique in its ability to efficiently produce multi-carbon products, and nanoporous Cu (NPC) derived from brass dealloying has emerged as a promising candidate. However, fundamental understanding of both brass dealloying and CO₂RR mechanisms remains incomplete. This thesis advances knowledge in both areas.
In Chapter 3, we introduce CO Displacement, a new method to quantify active sites for CO(2)RR on Cu-based nanomaterials. Comparison with the conventional double-layer capacitance method across four nanostructured electrodes validated its accuracy. We confirm that electropolished Cu exhibits the highest intrinsic activity, and our findings suggest under-coordinated Cu atoms are the true active sites for CO₂RR. Chapter 4 explores NPC synthesis by chemical dealloying of Cu20Zn80 in 5 M H3PO4 at varied temperatures, yielding tuneable ligament sizes from tens of nanometres to micrometres. In situ synchrotron X-ray diffraction (XRD) and cryogenic-atom probe tomography (cryo-APT) reveal complex phase transformations during dealloying. We further propose a method based on XRD peak asymmetry to estimate under-coordinated atom density, expressed as ligament surface strain. Finally, electrochemical CO2 and CO reduction measurements using H-cell and electrochemical mass spectrometry (EC-MS) respectively demonstrate superior performance of NPC relative to polycrystalline Cu. A linear relationship between the CO intrinsic activity and ligament surface strain was found for CO2RR, and an optimal ligament surface strain value was also observed for the CO reduction of NPC on EC-MS. These results further suggest that under-coordinated Cu atoms are the active sites for CO(2)RR. Hence, this work establishes novel scientific methods for analysing nano-porous materials for electro-catalysis, with broad applicability to other nano-structured catalysts, as well as mechanistic insights into both dealloying of brass and electrochemical CO2 and CO reduction.Open Acces
Parental involvement in infection prevention and control in low- and middle-income country neonatal units: a scoping review
No full textObjective
To review the literature on caregiver involvement in infection prevention and control in low- and middle-income country (LMIC) neonatal units (NNUs).
Introduction
There is a high burden and mortality of neonatal infections globally, with most of the burden falling on LMIC. Healthcare-associated infections (HCAIs) are a particular challenge, with neonatal sepsis being one of the most common HCAIs. It is urgent to prevent infections, as both identification and treatment of neonatal sepsis are increasingly difficult in these contexts. Parents are consistently present on NNUs but their involvement in infection prevention and control (IPC) has been underexplored.
Inclusion criteria
Included studies were carried out in LMIC NNUs and reported on caregivers’ involvement in design, implementation or experience of IPC interventions.
Methods
Five databases were searched in four languages and were screened by two authors. Reference searching was carried out of included papers. Data were analysed by each sub-question; caregiver involvement in intervention design (descriptive analysis), caregiver involvement in IPC delivery (quantitative analysis) and caregiver experience of hygiene and care (thematic analysis).
Results
38 studies were included. Caregiver involvement in IPC design was limited, with examples from four papers. 30 papers contained information about caregiver delivery of IPC interventions. Most activities were related to being educated on IPC, carrying out core IPC activities or providing a specific aspect of an intervention (most frequently Kangaroo Mother Care). 10 papers discussed caregiver experience of NNU hygiene including ethnographic accounts from Ghana, Malawi, Mexico, India and Brazil. Across all contexts hierarchical social structures and challenging communication between healthcare professionals and families was a barrier to effective IPC within NNUs. Families showed a good understanding of core IPC practices and an awareness of contextual challenges of IPC.
Conclusion
Caregiver involvement in IPC is limited to date. However, interventions such as Kangaroo Mother Care indicate the benefits that can be achieved. Hierarchical structures and communication challenges between healthcare professionals and families are a barrier to inclusion at present and must be addressed in any designed intervention
The impact of global warming on U.S. hurricane landfall: a storyline approach
No full textThe projection of hurricane activity under climate change is challenging. The Imperial College Storm Model (IRIS) was used to analyse the impact of global warming on North Atlantic hurricane landfall through a storyline approach. The storyline assumes increases of potential intensity (PI) as the cause of change with no changes to tracks or basin frequency. This allows study of both recent
trends and projections for the first time in a consistent way. The observed hurricane intensification is simulated but underestimated. For a +2◦C global warming scenario hurricanes of intensity Category 4 and above become 62% more likely in the basin and nearly twice (92%) more likely at landfall. The future number of hurricanes, their decay and tracks are uncertain and their impact is examined by sensitivity studies. Reduction of the basin count offsets warming driven landfall frequency increases only for weaker hurricanes. The increased frequency and fraction of the most damaging landfalling hurricanes is controlled by changes in PI
Quality by digital design to accelerate sustainable medicines development
No full textWe present a shared industry-academic perspective on the principles and opportunities for Quality by Digital Design (QbDD) as a framework to accelerate medicines development and enable regulatory innovation for new medicines approvals. This approach exploits emerging capabilities in industrial digital technologies to achieve robust control strategies assuring product quality and patient safety whilst reducing development time/costs, improving research and development efficiency, embedding sustainability into new products and processes, and promoting supply chain resilience. Key QbDD drivers include the opportunity for new scientific understanding and advanced simulation and model-driven, automated experimental approaches. QbDD accelerates the identification and exploration of more robust design spaces. Opportunities to optimise multiple objectives emerge in route selection, manufacturability and sustainability whilst assuring product quality. Challenges to QbDD adoption include siloed data and information sources across development stages, gaps in predictive capabilities, and the current extensive reliance on empirical knowledge and judgement. These challenges can be addressed via QbDD workflows; model-driven experimental design to collect and structure findable, accessible, interoperable and reusable (FAIR) data; and chemistry, manufacturing and control ontologies for shareable and reusable knowledge. Additionally, improved product, process, and performance predictive tools must be developed and exploited to provide a holistic end-to-end development approach
Stochastic dark sector
No full textCosmology probes the largest scales of the Universe, and quantum gravity the smallest. In this thesis, within the framework of quantum gravity phenomenology, we explore how stochastic effects in the dynamics of the dark sector can bridge those regimes.
We first study covariant Brownian motion as an effective signature of spacetime discreteness. We derive the process from first principles via Fokker-Planck and Langevin perspectives, and show its uniqueness when minimally coupled to curvature. Applied to dark matter particles, the resulting stochastic dark matter is governed by a single diffusion rate. We solve for the linear perturbations semi-analytically and numerically, showing that the model suppresses the matter power spectrum at small scales and offers a resolution to the discrepancy between CMB and low-redshift probes.
We then extend the framework to massless particles. We solve the modified Boltzmann equation analytically in an FRW spacetime, showing that diffusion impacts long-wavelength modes most strongly. We show that a future detection of a stochastic gravitational-wave background with LISA can improve current CMB bounds on the diffusion and drift parameters by over twelve orders of magnitude.
Finally, we examine Everpresent , a stochastic model of dark energy. A key feature of this model is that fluctuates and tracks the dominant energy density in order to resolve the cosmological-constant puzzle without fine-tuning. Accounting for initial conditions, we find hints that the nonlocality in the model is capable of producing inflationary expansion for many e-folds. A subset of Everpresent- realisations fit SN Ia data better than CDM, but the model struggles at describing CMB. We also study the allowed fluctuations of dark-energy density in a more model-independent manner, and find that some variation, especially prior to recombination, can lead to improvements over CDM; but the favoured fluctuations are smaller than is typical in Everpresent .Open Acces