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Localised stress and strain distribution in sliding
Get PDFIn this paper we present a comprehensive analysis of the contact mechanics and surface deformation associated with a micron-sized sliding contact, a critical process associated with abrasive wear. Using nanoscratch testing, we experimentally probe the surface deformation from a sharp contact. High-Resolution Electron Backscatter Diffraction (HR-EBSD) was used to characterise the stress and strain fields in the residual nanoscratch, in multiple planes. The experiments are simulated using a physically-based Crystal Plasticity Finite Element (CPFE) model, enabling a three-dimensional model that accurately captures the measured elastic and plastic strain fields around the sliding contact and allows assessment of the evolving deformation fields under load. This knowledge serves as a foundation from which we may be able to understand more complex wear situations and discern the multiphysical processes governing microscale wear
Expansion of forest cover and coeval shifts in Later Stone Age land-use at Taforalt and Rhafas Caves, Morocco, as inferred from carbon isotopes in ungulate tooth enamel
Get PDFLater Stone Age (Iberomaurusian) hunter-gatherer groups in northwestern Africa appear to have experienced a major reorganization of land-use strategies and settlement dynamics around 15–13 cal ka BP, which broadly corresponds to the globally recognized Greenland Interstadial 1 (Bølling-Allerød) climate interval. However, our understanding of the local impacts of this interval on environments in Morocco is incomplete, as is our understanding of the strength of the relationship, if any, between paleoenvironmental change and human behavior in the Moroccan Later Stone Age. This paper reconstructs changes through time in local forest canopy cover during the Later Stone Age around the archaeological cave sites of Taforalt and Rhafas (northeastern Morocco), using stable isotopes of carbon in ungulate tooth enamel. Results indicate a close link between tree cover expansion during Greenland Interstadial 1 and changes in land-use behaviors, which at Taforalt included the exploitation of storable oak and pine-derived plant foods and greater intensity of site occupation. High local productivity of nut-bearing trees paired with regional increases in human population densities likely contributed to greater intensity of occupations at Taforalt and Rhafas during Greenland Interstadial 1
Oriented naphthalene-O-propylammonium-based (NOP)4AuBIIII8 (B = Au, Bi, Sb) Ruddlesden–Popper two-dimensional gold double perovskite thin films featuring high charge-carrier mobility
Get PDFTwo-dimensional perovskites show intriguing optoelectronic properties due to their anisotropic structure and multiple quantum well structure. Here, we report the first three gold-based Ruddlesden–Popper type two-dimensional double perovskites with a general formula (NOP)4AuIBIIII8 (B = Au, Bi, Sb) employing naphthalene-O-propylammonium (NOP) as an organic cation. They were found to form highly crystalline thin films on various substrates, predominantly oriented in the [001] direction featuring continuous, crack-free film areas on the μm2 scale. The thin films show strong optical absorption in the visible region, with band gap energies between 1.48 and 2.32 eV. Density functional theory calculations support the experimentally obtained band gap energies and predict high charge-carrier mobilities and effective charge separation. A comprehensive study with time-resolved microwave conductivity (TRMC) and optical-pump-THz-probe (OPTP) spectroscopy revealed high charge-carrier mobilities for lead-free two-dimensional perovskites of 4.0 ± 0.2 cm2(V s)−1 and charge-carrier lifetimes in the range of μs. Photoconductivity measurements under 1 sun illumination demonstrated the material’s application as a photodetector, showing a 2-fold increase in conductivity when exposed to light
Synergistic and Additive Effects of Multiple Threats Erode Phylogenetic and Life History Strategy Diversity in Testudines and Crocodilia
Get PDFUnderstanding how multiple threats interact is crucial for the prioritisation of conservation measures. Here, we investigate how interactions between six common threats (climate change, habitat disturbance, global trade, overconsumption, pollution and emerging diseases/invasive species) reduce the life history strategy diversity and phylogenetic diversity of 230 species of Testudines and 21 of Crocodilia. We classify threat interactions into additive, synergistic and antagonistic according to the reduction of life history strategy and phylogenetic diversity. Most threat interactions are antagonistic; the effect of threats jointly is lower than the sum of the effects of threats separately. However, we find that the interaction between emerging diseases or invasive species with other threats has synergistic and additive effects, meaning that the combined effects are greater than or equal to the effects of threats separately. Our work can help target conservation strategies and detect key places to address multiple threats when they appear together
Regulatory T cells define affinity thresholds for CD8 + T cell tumor infiltration
Get PDFTCR repertoires against tumors lack high-affinity TCRs and are further suppressed by Tregs. We hypothesized that Treg depletion enhances the antitumor efficacy of low-affinity T cells. Using the weak agonistic peptide A4Y derived from LCMV glycoprotein peptide p33 as a model antigen and VLPs as a vaccine platform, we tested this approach. In a separate low-affinity model, we targeted B16F10 melanoma with our multi-target vaccine. Results revealed limited in vivo lytic cross-reactivity between A4Y and p33 peptides, and the A4Y-vaccine alone failed to inhibit B16F10p33 tumor progression. However, combining A4Y-vaccine with Treg depletion triggered a robust immune response, characterized by increased CD8+ T cell infiltration, enhanced T cell functionality, and tumor-free survival. Infiltrating T cells also exhibited closer spatial proximity and heightened migration from blood vessels. Similarly, combining low-affinity vaccine with Treg depletion enhanced antitumor responses. These findings highlight the potential of Treg depletion to advance vaccination strategies targeting TAAs with low-affinity T cells
The impact of weight loss programmes on disordered eating
Get PDFThe prevalence of obesity is increasing globally. Significant weight loss is an effective strategy to manage the condition, as well as manage conditions associated with obesity, like type 2 diabetes (T2D). However, alongside the prevalence of obesity and T2D, the prevalence of eating disorders is equally increasing globally. Eating disorders can be devastating for people who experience them, and they often co-exist with overweight/obesity and T2D, therefore offering weight loss treatments to this population could be considered risky. In 2020, NHS England announced the roll-out of the NHS Path to Remission programme for people living with overweight/obesity and T2D, which offered total diet replacement (TDR) targeted at significant weight loss and diabetes remission. Concerns on the impact of the programme on disordered eating emerged.
The research in this thesis aimed to investigate the impact of weight loss programmes, including TDR, on disordered eating. I initially conducted a systematic review and meta-analysis to explore the impact of weight loss programmes, either alone or paired with psychological support intervention or pharmacotherapy on disordered eating scores, regardless of baseline disordered eating status. I found that weight loss programmes were associated with a consistent reduction in disordered eating in the end of the intervention and at a further follow-up. In sub-group analyses, disordered eating scores reduced more in people with an eating disorder at baseline compared with people without high scores, and there was no evidence the association depended upon intervention type. The review only identified two studies using more rigid interventions like low-energy diet replacement, where I hypothesised the risks would be greater. As a result, I designed and conducted a non-inferiority randomised controlled trial, investigating the impact of a TDR programme on disordered eating scores in people living with overweight/obesity, T2D and disordered eating at baseline. Disordered eating and its impairment reduced significantly in the intervention arm compared to the control group, and so did depressive symptoms and diabetes distress. No participant was judged to be at high suspicion for having developed a new eating disorder. I also analysed recordings of the dietetic sessions qualitatively, to identify similarities and differences in experiences of people participating in a TDR programme according to their disordered eating score trajectories.
Participants with worsening disordered eating scores or of variable pattern of change throughout the trial reported eating usually in response to emotions and boredom, and experiencing significant hunger during the TDR phase, as well as a non-supporting environment. This often resulted in non-adherence and unsuccessful attempts to return to the programme. Participants who experienced stable or reducing disordered eating scores throughout the trial also experienced hunger but were often able to manage it and continue on the programme. Combining qualitative and quantitative data from this research, I concluded that weight loss programmes including TDR, are associated with reductions in disordered eating scores in the short term; longer term impact could be explored in future research
Handheld spatially offset raman spectroscopy for rapid non-invasive detection of ethylene glycol and diethylene glycol in medicinal syrups
Get PDFWe investigate the potential of Spatially Offset Raman Spectroscopy (SORS) as a rapid, non-invasive screening tool deployable in the field to detect diethylene glycol (DEG) and ethylene glycol (EG) in medicinal syrups within closed containers. Measurements were performed on neat propylene glycol (PG) and glycerol, key components of many medicinal syrups, as well as marketed medicinal syrup formulations spiked with DEG and EG at various concentration levels to assess the technique’s limit of detection in real-life samples. SORS was able to detect these down to ~0.5% concentration level in neat PG for both DEG and EG compounds and ~1% concentration level for DEG and EG in neat glycerol. The DEG and EG detection thresholds for the marketed formulations measured through original bottles was ~1%, for Benylin (active ingredient: Glycerol) and Piriteze (active ingredient: Cetirizine Hydrochloride). For Calpol (active ingredient: Paracetamol) the detection limit was higher, ~2% for EG and ~5% for DEG. Although not reaching the International Pharmacopeial 0.1% detection threshold currently required for purity checks for human consumption, the method can still be used to detect products where DEG or EG has been wrongly used instead of PG or glycerol or if present in large quantities. The technique could also be used for raw material identification testing to ensure no mislabelling has occurred in pre-production stages and as a screening device in distribution chains to detect major deviations from permitted content in non-diffusely scattering, clear formulations, to help prevent serious adverse outcomes, such as acute renal failure and deaths
Baseline serum ferritin predicts myocardial iron uptake following intravenous iron therapy – a hypothesis‐generating study
Get PDFAims: Many patients with heart failure (HF) are iron‐deficient. Intravenous (IV) iron therapy improves symptoms and reduces hospitalizations for HF. Several mechanisms have been proposed, including myocardial iron repletion. However, it is unknown if serum iron markers predict the extent of this repletion. To address this question, data from two clinical studies that evaluated changes in myocardial iron using cardiac magnetic resonance (CMR) were harnessed. Methods and results: The Myocardial‐IRON trial measured change in myocardial iron, denoted by a decrease in CMR T1 and T2*, at 7 and 30 days after IV ferric carboxymaltose (FCM) in patients with iron deficiency (ID) and HF (n = 53). The STUDY trial measured myocardial and spleen iron at multiple timepoints after FCM in patients with ID without HF (n = 12). In this post‐hoc analysis, we examined the association between baseline serum iron markers (transferrin saturation and ferritin) and change in myocardial iron in the weeks after FCM therapy. Changes in spleen iron were also examined, due its role as an intermediary in the redistribution of iron from iron‐carbohydrate complexes such as FCM. In patients with or without HF, higher serum ferritin at baseline predicted lower rise in myocardial iron in the weeks after therapy with FCM. In contrast, higher serum ferritin at baseline predicted a greater rise in spleen iron. Conclusions: These data point towards the hypothesis that functional ID, which is characterized by elevated ferritin, could limit myocardial iron repletion after IV iron therapy, by favouring iron trapping in the spleen
A handful of data: evaluating few–shot incremental landmark detection
No full textWhile automated landmark detection in medical imaging has achieved remarkable accuracy, it still requires sufficiently annotated datasets. This remains a significant barrier to clinical adoption. This paper investigates the effect of the number of annotations available on the model performance without relying on overly specialised few-shot configurations. We explore two practical scenarios: landmark detection with limited annotated data (≤ 60), and the incremental addition of new landmarks to existing models. Through experiments on hand radiographs, we demonstrate that models trained on just a fraction of the full dataset can achieve an accuracy comparable to that of other methods. Furthermore, we show that new landmarks can be effectively learnt through fine-tuning with as few as five examples, though performance varies with landmark variance. Also, we validate weight initialisation performance and find fine-tuning from prior landmark models tend to under-perform. Our findings suggest that the relationship between the amount of annotated training data and detection accuracy is nonlinear, with diminishing accuracy gains beyond certain thresholds. This insight has important implications for clinical practice, suggesting that label-efficient, modular landmark detection systems are valuable options, particularly when sub-millimetre precision is not critical