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Exploring geographic differences in IgE response through network and manifold analyses
No full textBackground: Component-resolved diagnostics allow detailed assessment of IgE sensitization to multiple allergenic molecules (component-specific IgEs, or c-sIgEs) and may be useful for asthma diagnosis. However, to effectively use component-resolved diagnostics across diverse settings, it is crucial to account for geographic differences.Objective: We investigated spatial determinants of c-sIgE networks to facilitate development of diagnostic algorithms applicable globally.Methods: We used multiplex component-resolved diagnostics array to measure c-sIgE to 112 proteins in an international collaboration of several studies: WASP (World Asthma Phenotypes; United Kingdom, New Zealand, Brazil, Ecuador, and Uganda), U-BIOPRED (Unbiased Biomarkers for the Prediction of Respiratory Disease Outcomes; 7 European countries), and MAAS (Manchester Asthma and Allergy Study, a UK population-based birth cohort). Hierarchical clustering on low-dimensional representation of co-occurrence networks ascertained sensitization and c-sigE clusters across populations. Cross-country comparisons focused on a common subset of 18 c-sIgEs. We investigated sensitization networks across regions in relation to asthma severity.Results: Sensitization profiles shared similarities across regions. For 18 c-sIgEs shared across study populations, the response structure enabled differentiation between different geographic areas and study designs, revealing 3 clusters: (1) Uganda, Ecuador, and Brazil, (2) U-BIOPRED children and adults, and (3) New Zealand, United Kingdom, and MAAS. Spectral clustering identified differences between clusters. We observed constant, almost parallel shifts between severe and nonsevere asthma in each country.Conclusions: Patterns of c-sIgE response reflect geographic location and study design. However, despite geographic differences in c-sIgE networks, there is a remarkably consistent shift between networks of subjects with nonsevere and severe asthma
Single-cell and spatial profiling highlights TB-induced myofibroblasts as drivers of lung pathology
No full textTuberculosis (TB) typically causes lung destruction and fibrosis, leading to ∼1.3 million deaths annually. The cellular drivers of human TB immunopathology remain poorly defined. We performed single-cell RNA sequencing and spatial transcriptomics on lung tissues from TB-infected and TB-negative individuals, identifying 30 distinct immune, parenchymal, and stromal cell subsets. Several were linked to TB pathology and corroborated through immunohistochemistry, flow cytometry, and independent human datasets. Fibroblasts were identified as major drivers in both active TB granuloma and TB-diseased lung tissue. In particular, the MMP1+CXCL5+ fibroblast subset, expressing a myofibroblast-like gene signature, was associated with severe disease and higher bacterial burden in nonhuman primate granulomas. Network analyses revealed cross talk between MMP1+CXCL5+ fibroblasts and SPP1+ macrophages within the granuloma cuff, which has been reported in other disease contexts, and may play an important role in TB immunopathology. Our findings highlight previously unappreciated cell populations and potential targets for novel TB therapies
From folds to functions: programmable origami curvatures enable shape reconfigurable metasurfaces for antenna design
No full textFantasie Nègre: Four Fantasies for Piano by Florence B. Price
No full textAn historic addition to the advanced keyboard repertoire, this edition presents Florence B. Price's Four Fantasies for Piano in their entirety for the first time, honouring the composer's development of the Fantasie Nègre genre into a collective body of works. This critical edition foregrounds Price's original, unrevised manuscripts, most notably in the case of No. 4, and presents Ege's meticulous reconstruction of the incomplete, presumed lost, third Fantasie. It also serves as a performing edition, drawing on Ege's significant performance history with this work to include fingerings, redistributions of notes between hands, and additional dynamic and tempo markings, as well as detailed performance notes. This is a spectacular set of virtuosic pieces that showcases Price's ability to blend African American folk idioms and traditional forms with her own unique musical language
WiIID: Wi-Fi based intelligent indoor intrusion detection with tensor decomposition
No full textWi-Fi sensing has emerged as a promising paradigm for indoor intrusion detection, as it offers a robust and highaccuracy solution without the need for extra hardware deployment. However, existing schemes often compromise the inherent structure of channel state information (CSI) during feature extraction through lossy preprocessing, causing high false alarm rates and poor generalization. As a remedy, we propose a novel tensor-based framework for indoor intrusion detection, which enables reliable perception of fine-grained human activities through structured feature extraction, even in motion-ambiguous scenarios. Our approach integrates tensor-based feature extraction, multi-dimensional feature consolidation, and a modified deep learning (DL) network for accurate intrusion recognition. To validate our framework, we collected a comprehensive throughwall CSI dataset under the IEEE 802.11n standard, encompassing five common human activities in realistic scenarios. Extensive experimental results demonstrate the superior performance of our method compared to existing state-of-the-art schemes
Ultrasonic tool to cut human bone: cutting speed and forces necessary for potential remote robotic arms
No full textProcedural-related musculoskeletal pain is common among orthopaedic surgeons, often caused by the repetitive use of high-force bone-cutting tools. Ultrasonic cutting devices, which can operate with lower force, may help reduce this physical burden. In this study, three practising orthopaedic surgeons each performed two cuts on three fresh cortical bone samples, harvested from excised femoral necks from three patients undergoing hip replacement surgery. The study was conducted using an ultrasonic cutting device in a controlled yet clinically reflective environment. A novel setup captured real-time data on surgeon-related parameters, including vertical cutting force and vertical and horizontal cutting speed. Consistent with previous research, we confirmed that ultrasonic devices enable low force cutting (average 1.91 N). However, our findings revealed significant variability in how each surgeon interacted with the device - including how much force each surgeon applied, and how the device was manoeuvred which can influence device performance, thermal effects, and overall clinical outcomes. Given the critical importance of surgeon-related factors, our results highlight the need to understand how each surgeon interacts with these devices differently. This insight can inform training and device optimisation strategies; help translate bench testing results into effective clinical use and ultimately improve surgical performance and patient outcomes. Additionally, our findings support the potential benefits of integrating ultrasonic devices with robotic platforms to maintain consistent cutting parameters. Future research should investigate optimal cutting parameters, evaluate different blade profiles, assess result generalisability and compare outcomes before and after training or system enhancements.</p
Supporting families with unsettled babies - development of a digital intervention
No full textBackground Unsettled baby behaviours, such as crying and vomiting, are common but distressing for families. Unsettled behaviours are increasingly attributed to medical causes such as reflux or cows’ milk allergy. When inaccurate, this causes unnecessary harm to families and healthcare systems. Existing interventions to support parents managing unsettled babies are costly and often biased by conflicts of interest from the formula milk industry. Aims To co-design a person-, theory- and evidence-based behavioural intervention supporting families with unsettled babies. Method Qualitative interviews and the person-based approach (PBA) were combined with innovative methods including partnership working with underserved communities. Firstly, a systematic review and thematic synthesis explored parent experiences of unsettled babies, with an emphasis on parents’ thoughts and feelings about medical labels. An explanatory, conceptual model was proposed summarising parent experiences when faced with a baby they perceive as unsettled. Next, a qualitative interview study aimed to deepen understanding of parent attitudes to medical labels using an ethnically diverse sample of 25 mothers. Hybrid inductive & deductive analysis was used, including reflective thematic analysis, negative case analysis and framework analysis. Themes were presented and the conceptual model was refined. Finally, an intervention was developed using behaviour change theory and the PBA. This was optimised through qualitative ‘think-aloud’ interviews with 22 parents, analysed through thematic analysis and a table of changes. Findings Key findings from the systematic review and qualitative interviews offer a new insight into the thoughts, feelings and motivations of parents with unsettled babies. Findings suggest parents report a sense of guilt or failure, driving a search for an external, medical cause of unsettled behaviour. A novel intervention was developed. This aims to help parents distinguish normal baby behaviour from medical red flags; increase parent self-efficacy and give tools to self-manage unsettled behaviours. Discussion The results of this work are put in the context of wider literature on medically unexplained symptoms, the transition to parenthood, parenting self-efficacy and bonding. Limitations and strengths of the research, suggestions for future research and clinical practice are discussed. Conclusion The resulting intervention, if nested within a wider system of support, may provide help to families of unsettled babies, reducing unnecessary medicalisation
Testing methods of initiating inter-generational interactions on energy in the home
No full textFor the UK to reach the strict emissions targets set within the 2008 Climate Change Act, significant reductions in energy consumption and emissions must be made across every sector. Whilst many new energy initiatives aimed at improving existing homes have been launched (and closed) over the years, the fact remains that the UK now has amongst the worst-performing homes in Europe. To add to this, the rising cost of living, particularly of utilities, is putting ever-increasing strain on residents. To address these issues, alternative solutions that are affordable and achievable are being explored. Improving occupant energy literacy and environmental awareness could be an approach to achieving reductions in home energy consumption. A potentially influencing factor in the home is children. As agents of change, children may disseminate environmental knowledge to older generations. This could be an effective way of improving their parents’ energy literacy and in turn their energy behaviour decisions.This research tested four different methods of initiating inter-generational interactions on energy in the home. It investigated what topics and content would support improvements in energy literacy, for both children and adults, as well as how to teach this content to children. Interventions tested the differences between teaching online at home or teaching in person within the school environment. Differing types of home activities, each intended to create a potential for the interaction to take place, were tested, ranging from simple ’Snakes and ladders’ style games for children to play with their parents, to gamified continuous data logging of home energy behaviour by the participating children. A re-playable longitudinal intervention was also testedResults overall suggested that children learnt more effectively within the school environment compared to the online home environment. It also highlighted that just one single lesson is enough to improve the energy literacy of children about ‘energy in the home’ – although an ‘Eco Day’, comprising of several lessons and varying environmental topics, seemed to have a longer-lasting effect on the children. When considering the intergeneration interactions, all methods showed promising results when gathering feedback from parents about interactions and conversations with their children. Parents reported that they intended to sustain behavioural changes that they had made due to the intervention.Method one reinforced the rationale behind the need for inter-generational influences as it showed homes with children consumed more energy than both those without and those with elderly dependants.Method two (in the school context) found that primary-aged children responded well to scientific topics traditionally not taught until secondary school such as energy sources and embodied carbon. Participating parents stated knowledge was passed on to them through the interactions created by the intervention’s home activities.Method three (in the home context) utilised gas meter readings before, during and after an intervention and showed that as the number of interactions with the intervention’s ’Kids4climate website’ increased, rates of gas consumption decreased. Having said that, several significant outside factors affected this study; namely the outbreak of COVID-19, war between Russia and Ukraine and most influentially, the UK price cap on energy being increased several times.Method four (in the school context) reported that "concern for climate change" and "Consideration of environmental impacts of decisions" both declined throughout the study for the control group. Whereas the intervention group maintained their high levels of concern and consideration, suggesting a positive influence from the intervention.This research has successfully shown that several methods can be used to initiate intergenerational energy interactions in the home. Although their effectiveness varied, both ‘online’ and ‘in-person’ interventions can be used to increase and improve child-to-adult interactions and in turn positively influence energy decisions in the home. In terms of the practical applications of this research, it has been shown that at the small scale of this research, improving the energy literacy levels of children and providing the opportunity for inter-generational interaction to take place can lead to better energy decisions being made by the main occupants in the home. It is a recommendation from this research that energy literacy should be incorporated into the next edition of the National Curriculum
Rethinking legal approaches to electronic bills of lading: from functional equivalence to a substantive approach
No full textThe transition from paper-based to electronic bills of lading represents a significant advancement in global trade, promising enhanced efficiency and security. However, this transition also raises complex regulatory challenges. Among the regulatory approaches, functional equivalence has become the cornerstone for legitimizing electronic bills of lading. Scholarship and practice have largely embraced this principle without subjecting it to sustained critical scrutiny, although a few scholars have questioned its limitations in the legal context. In other words, although functional equivalence has been widely accepted, its limitations in the legal context remain underexplored. This research aims to critically evaluate functional equivalence and explore potential alternative approaches to better address the emerging challenges posed by new technologies. This research will first examine the theoretical underpinnings and historical foundations of functional equivalence. It will trace how this concept entered the field of law and became a regulatory approach for electronic records, including electronic bills of lading. The study will then evaluate how the principle was articulated in UNCITRAL's exploration of e-commerce and assess its adequacy in regulating electronic bills of lading, thereby laying the groundwork for a critical examination of its limitations.Beyond evaluating functional equivalence, this thesis also draws on the regulatory explorations of other international organisations. The proposed substantive approach on controlled electronic records highlights issues of control, proprietary rights, and custody, offering a distinct perspective. Building on these insights, this thesis proposes a substantive approach as an alternative framework for regulating electronic bills of lading. This approach aims to move beyond functional equivalence by directly addressing the substantive legal requirements of electronic bills of lading
Spoilage traits and control of Brettanomyces bruxellensis: advances and implications for winemaking
No full textBackground: Brettanomyces bruxellensis (B. bruxellensis) is a persistent spoilage organism of beverage fermentations, capable of producing volatile phenols that compromise product aroma and quality, particularly in wine. The yeast is highly adapted to the winery environment, withstanding acidity, ethanol, and nutrient limitations. Its various traits exacerbate its detection and elimination. Current chemical controls have limitations, thereby increasing the call for biological alternatives. Scope and approach: We review available literature to define the scope of the B. bruxellensis problem, its impact on beverages and the traits aiding its survival and recalcitrance. The basis of these, namely the viable but non-culturable (VBNC) state, biofilm formation, nutritional versatility and high genetic/phenotypic diversity is delineated. We provide a comprehensive summary of reported inhibitors of B. bruxellensis, their mode of action, advantages and disadvantages, performance in laboratory and/or industrial contexts, and commercial availability. Included are strategies based on sulfur dioxide (SO2), chitosan, or dimethyl dicarbonate, and those based on killer toxins, antimicrobial peptides and iron chelators. Key findings and conclusions: Currently, the most effective and common control for B. bruxellensis is the application of SO2. But increasingly tolerant strains are appearing and consumer preferences or allergies to SO2 highlight the critical need for better control agents. Several biological solutions, particularly those based on non-Saccharomyces yeasts, show promise but further research is needed. Importantly, future progress in controlling B. bruxellensis will depend on multi-strain efficacy testing, advanced detection methods to identify VBNC and biofilm associated cells, and the integration of complementary agents tailored to the wine or relevant substrate
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