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Mechanistic and data-driven modelling of powder adhesion
No full textPowder adhesion to punch surfaces (“sticking”) is a persistent, costly problem in pharmaceutical tablet manufacturing. This thesis addresses critical gaps by uniting data-driven prediction, high-fidelity image analysis, and continuum mechanics in a multi-scale framework spanning molecules, micrographs, and process physics.First, the chemical basis of sticking is quantified using molecular descriptors. A data-driven pipeline compresses more than > 1 800 descriptors into a five-component fingerprint that perfectly separates the sticking behavior of 42 benchmark powders, establishing (for the first time) a cheminformatics route to predict tablet manufacturability.Next, a novel rotation-robust feature-extraction architecture is introduced for 834 punch-face micrographs. Equal-area, staggered annular-sector partitions encode axial symmetry and support a topology-aware discrimination strategy derived from observed sticking patterns. Coupled with a semi-guided segmentation network (F1 > 0.97), the method yields spatially resolved sticking maps that decouple where adhesion occurs from how strongly it occurs. Hierarchical statistical analysis identifies material-specific controls: temperature predominantly governs sticking in acetylsalicylic acid, humidity primarily influences mannitol, and all materials exhibit suppressed sticking near the punch edge.Lastly, thermo-mechanically coupled finite-element simulations elucidate underlying mechanisms. Die-wall friction induces radial stress and density gradients; during punch retraction these gradients drive mixed-mode interfacial separation, concentrating tensile stresses away from the edge—the same locations where high sticking probability is observed. A multilayer-perceptron surrogate trained on simulated fields predicts local sticking with high fidelity, linking material attributes, process conditions, and observed defects.Together, the contributions deliver standardized, spatially explicit metrics for powder adhesion and a rigorous methodology for comparing materials and processes. The framework integrates molecular fingerprints, image-derived sticking maps, and physics-based fields, laying foundations for predictive, mechanistic sticking models and enabling quantitative strategies to mitigate a critical manufacturing loss mode.</p
Modulatory Effect of Alarmins in Immune and Structural Cells: Implication for Asthma Pathogenesis and Clinical Relevance
No full textBackground: Asthma is a heterogeneous disease characterized by airway hyperresponsiveness (AHR) and inflammation. Alarmins, including TSLP, IL-33, and IL-25 (IL-17E), are released by epithelial cells in response to environmental triggers and play a crucial role in shaping immune responses. These cytokines contribute to airway inflammation and have emerged as potential therapeutic targets. While their role in Th2 inflammation is well established, their effects on airway smooth muscle (ASM) responsiveness, immune cell activation (PBMCs, CD4+T cells, and CD8+T cells), and the transcriptional regulation of CD4+T cells remain incompletely understood. Methods: (i) Tracheal rings from C57BL/6 mice, divided into upper and lower parts, were cultured in DMEM with recombinant mouse TSLP, IL-33, and/or IL-17E (IL-25) at 100 ng/ml for 24 hours. Contraction to carbachol (CCh) and relaxation to formoterol were then assessed using the DMT organ bath system. (ii) Human PBMCs, CD4+T cells, and CD8+T cells from healthy donors were pre-treated with recombinant human TSLP, IL-33, and /or IL-17E (IL-25) 100 ng/ml for 24 hours prior to TCR engagement aCD3 (anti-CD3) 1 μg/ml/ aCD28 (anti-CD28) 2 μg/ml for 4 days, and the anti-inflammatory effect of dexamethasone were assessed at different time point during stimulation. (iii) Transcriptome responses in isolated healthy CD4+T cells, with or without combined alarmin cytokines stimulation (100ng/ml), were assessed by RNA-seq. Results: (i) Contractile responses to carbachol (CCh) were enhanced in tracheal ring treated with TSLP, while IL-25 decreased CCh-induced ASM contractility in both upper and lower tracheal rings. IL-33 had no effect on CCh-evoked responses. Notably, incubation with combined alarmins significantly reduced contractile responses in the lower parts. (ii) in immune cells, treatment of isolated CD4+T cells with alarmins led to a significant alter the TCR-induced cytokine production. All alarmins, either alone or in combination, enhanced IL-5 production. TSLP and combined alarmins significantly increased IL-10 and IFNg production, while TSLP and IL-33 significantly enhanced TNFa production. (iii) RNA-seq analysis revealed distinct gene expression changes in isolated healthy CD4+T cells treated with combined alarmins (100 ng/ml) under TCR activation conditions. Upregulated genes included SMN2, AFF3, GSTM1, and IRS1, whereas HLA-C, HLA-DQB1, HLA-DQA1, and AOAH were downregulated. Gene ontology analysis further showed that alarmins supressed pathways related to metabolism and immune activation, while enhancing those associated with protein transport and secretion compared with TCR activation alone. Conclusion: These findings demonstrate that alarmins differentially regulate ASM contractility, modulate TCR-induced cytokine production in immune cells, and reshape the transcriptional profile of CD4+T cells. Collectively, this highlights their pivotal role in orchestrating airway inflammation and immune responses and provides insight into their potential as therapeutic targeting in asthma.</p
Corporate Social Responsibility in Extractive Industries in Sierra Leone and Nigeria: A Comparative Study
No full textThe study investigates the role of CSR in addressing the social and environmental impacts of business activities in Nigeria and Sierra Leone’s extractive industries. It mainly adopts a comparative approach to analyse the frameworks supporting CSR in both countries and how companies collaborate with multi-stakeholder groups to manage the adverse effects of their operations on external stakeholders.The study found that the current voluntary and self-regulatory CSR model does not encourage MNCs to adopt robust CSR practices in Sierra Leone and Nigeria. Poor CSR performance is linked to companies’ failing to strictly follow their CSR policy guidelines during implementation. Country-specific factors also contribute to CSR non-compliance. Weak institutions fail to create an environment suitable for effective CSR. Contrary to the notion that MNCs serve as agents for transferring responsible business practices in developing countries, the findings suggest that MNCs are less likely to use corporate resources to mitigate the impacts of their operations in environments with weak institutions. Corporate philanthropy is used primarily to mask corporate failures related to environmental and human rights issues.The contextually informed and evidence-based approach of the study highlights the lack of conditions necessary for effective CSR at both company and domestic levels, and that efforts to promote corporate responsibility and accountability should primarily focus on external supervisory controls. The study identifies practical solutions for improving social responsibility and accountability in both countries. It advocates for formal enforcement outside the CSR framework to safeguard human rights, given the impact of violations on local populations and global peace and security. Informal enforcement mechanisms, emphasising activism (NGOs and shareholder activism) and market controls (financial and investment institutions), can also operate to influence corporate behaviour beyond regulatory boundaries. The study contributes to CSR literature in Sierra Leone and Nigeria and global policy on the governance of MNCs.</p
The Hidden Graduate Career Stories - Hacking Social Capital - The 1 Hour Project
No full textWidening participation (WP) students – those from under-represented, low-income or first generation backgrounds – often remain “hidden talent” in the UK graduate labour market. Despite mass higher education, class-based disparities persist in graduate outcomes, with elite jobs and leadership roles dominated by those of higher socio-economic status. This practice-based doctoral research explores how storytelling can empower such hidden graduate talent and improve social mobility. Using the author’s own trajectory as a first generation university graduate and career practitioner as a springboard, the study develops a qualitative, practice-led approach combining the literature review, personal narrative, student interventions, graduate interviews and successful experiments. Key literature on social and cultural capital (Bourdieu), class and “doxa” in recruitment, impostor syndrome and confidence barrier, and asset-based recruitment models is critically reviewed to contextualise the challenges faced by working-class graduates. Methodologically, the project involved a storytelling-based intervention with current students and video-interviews with successful professionals from widening participation (WP) backgrounds. The findings reveal that structured storytelling exercises can significantly boost students’ confidence and narrative competence, helping them articulate diverse skills and “convert” their experiences into forms of capital valued by employers. Interviewees’ career stories highlighted the importance of turning points (such as mentorship, internships and personal resilience) in overcoming class barriers. Discussion of the findings indicates that storytelling is a powerful tool to bridge the cultural gap between WP graduates and the professional workplace, challenging traditional recruitment practices that often favour familiar “elite” narratives. The thesis proposes a practical toolkit for WP students at UK universities, the 1 Hour project. In conclusion, the research demonstrates that empowering students to reframe their personal journeys as strengths can improve their employability and challenge existing recruitment doxa, thereby supporting social mobility. It calls on higher education providers and employers to recognize and harness the rich, untapped narratives of hidden talent as a means to level the playing field in the graduate labour market.</p
Prevalence and patterns of multiple long-term conditions among lymphatic filariasis patients in Odisha, India: a community-based cross-sectional study
No full textIntroduction: Neglected tropical diseases (NTDs), such as lymphatic filariasis, mimic other chronic conditions and share common risk behaviors with parallel health system issues that require unique interventions. Multiple long-term conditions (MLTCs or multimorbidity), defined as two or more chronic conditions has become increasingly common in low- and middle-income countries (LMICs) such as India. However, data on the prevalence of the interface between NTDs and other chronic conditions are lacking. We estimated the prevalence and correlates of MLTC, assessed the commonly occurring patterns, and investigated the association between self-rated health (SRH) and the number of chronic conditions among patients with lymphatic filariasis. Methods: A cross-sectional study was conducted in Odisha, India, using a prevalidated MLTC assessment tool. We employed systematic random sampling to recruit 584 participants aged ≥ 18 years having lymphatic filariasis. MLTC was defined as the coexistence of one or more chronic conditions along with lymphatic filariasis. A multivariable logistic regression model was used to identify the correlates presented as adjusted odds ratios (AORs) with 95% confidence intervals (CIs). A hierarchical cluster analysis was conducted to identify the major clusters of chronic conditions. An ordinal regression model was used to assess the association between SRH and the number of chronic conditions. Results: The overall prevalence of MLTC was 68.8% (95% CI: 64.9–72.6), while the mean number of chronic conditions was 2 ± 2.3. The chance of having MLTCs was greater among males [AOR: 3.9 (95% CI: 2.1–7.3)] than females. Participants with education at the primary and secondary school levels had greater odds of having MLTC [AOR: 2.2 (95% CI: 1.3–3.7)] and [AOR: 2.3 (95% CI: 1.3–3.8)], respectively. The commonly observed triad was lymphatic filariasis with arthritis and peptic ulcer disease (1.5%), while the most common tetrad was lymphatic filariasis, hypertension, diabetes and peptic ulcer disease (0.7%). There was a per unit decrease in SRH with each additional chronic condition. Conclusion: We observed a high prevalence of MLTC among people with lymphatic filariasis. The findings of this study will not only be useful for both resource and planning in India but also in similar LMICs with a high burden of lymphatic filariasis.</p
Cardiac function and mechanics in systemic sclerosis: a systematic review and meta-analysis
No full textObjectives The study aimed to evaluate differences in conventional, tissue Doppler imaging (TDI) and speckle-tracking echocardiographic (STE) parameters of all cardiac chambers between SSc patients and healthy controls. Methods A study search strategy based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) was performed. MEDLINE, Scopus and Web of Science were searched using the following keywords: “speckle tracking”, “global strain”, “longitudinal strain”, “circumferential strain”, “radial strain”, “atrial strain”, “right ventricular strain”, or “left ventricular strain” and “systemic sclerosis”. Primary pooled analyses were performed on each cardiac parameter independently to determine the weighted mean difference (WMD) between SSc and controls. Further independent subgroup analyses were performed to compare symptomatic vs asymptomatic SSc and diffuse vs limited SSc. Results The systematic review and meta-analysis included 41 case–control eligible reports studies with a pooled sample size of 2497 SSc cases and 1439 controls. Significant weighted mean differences (WMD) between SSc patients and healthy controls were identified in septal S’ wave (WMD 0.343 cm/s, CI [− 0.540–0.145], I2: 36%, p = 0.001), lateral S’ wave (WMD 0.795 cm/s, CI [− 1.394–0.197], I2: 0%, p = 0.009), tricuspid S’ wave (WMD 1.137 cm/s, CI [− 1.784–0.489], I2: 84%, p = 0.001), septal e’ wave (WMD 1.398 cm/s, CI [− 2.272–0.523], I2: 82%, p = 0.002) and lateral e’ wave (WMD 3.545 cm/s, CI [− 4.990–2.100], I2: 71%, p < 0.001) velocities. STE parameters were attenuated in patients with SSc, with impairment of left ventricular global longitudinal (WMD 2.765%, CI [− 3.482–2.049], I2: 91%, p < 0.001), circumferential (WMD 3.145%, CI [− 4.181–2.109], I2: 79%, p < 0.001), and radial (WMD 4.044%, CI [− 6.199–1.889], I2: 0%, p < 0.001) strain, right ventricular free wall (WMD 4.492%, CI [− 6.048–2.937], I2: 76%, p < 0.001) and right ventricular global longitudinal strain (WMD 2.843%, CI [− 3.290–2.396], I2: 32%, p < 0.001), as well as left (WMD − 8.317%, CI [− 11.873–4.761], I2: 82%, p < 0.001) and right (WMD 7.346%, CI [− 10.536–4.156], I2: 26%, p < 0.001) atrial reservoir strain. Conclusion SSc is associated with significantly impaired cardiac function and mechanics compared to healthy individuals, even in the absence of symptoms or pulmonary hypertension. Graphical Abstract</p
The role of combining exercise with pharmacologic management of CKD: From SGLT2 and GLP-1 to broader therapeutic strategies
No full textNo description supplied</p
Reinterpretation of Bakiribu waridza from the Romualdo Formation (Lower Cretaceous) of Brazil: a fish not a pterosaur
No full textFragmentary fossil remains from the Romualdo Formation (LowerCretaceous) of Brazil, preserved in association with two fish were interpreted as twoindividuals of a new genus and species of ctenochasmatine pterosaur, Bakiribuwaridza Pêgas et al., 2025. Comparison with fossils from the same geological unitshow that the remains represent the gill arch apparatus of a large actinopterygianfish. A series of partially articulated bony elements correspond closely in morphologyto the ceratohyals, hypohyals, basibranchial and hypobranchials of amiid fish whilethe purported ‘teeth’, which lack enamel, dentine tubules and in most cases evidenceof a structure corresponding to a pulp cavity, are reinterpreted as gill filaments.Bakiribu waridza is a fish, not a pterosaur and the name, founded on indeterminateremains of an actinopterygian fish, possibly an amiid, should be treated as a nomendubium. Rather than a regurgitalite this association of several fish remains appearsto be a typical Romualdo Formation concretion. This reinterpretation of Bakiribu hasnegligible impact on our current understanding of the evolutionary history ofpterosaurs as ctenochasmatines represented, for example, by Pterodaustro, werealready known to be present in South America until the end of the Early Cretaceous.</p
The Sociogenesis Of A Village: From Wicked To ‘Wicked’
No full textThe research village’s history dates back over a millennium, with my family name, like many others, being traced back for centuries. Over time a cultural stock of symbols developed, expressing the feelings and attitudes of various stages of the historical development of processes of affective identification and disidentification. I examined the role of nostalgia and hauntology in these processes within the sociogenesis of the village, thereby making a novel sociological contribution. Different concepts, methods and data sources from various disciplines and subject areas were brought together in a multi-phased approach, providing a snapshot of life in an English rural village today, replete with its past which, through nostalgia and hauntology, is inextricably linked with its present. The village’s sociogenesis is more than a chronicling of events; it unravels and reveals the structure and the direction of changes of the developing process, unattainable without my diverse approach. The multidisciplinary synthesis and multi-phased approach has similarities with Norbert Elias’ processual sociology. However, my observations, document examination and in-depth interviews, using both current and former residents’ voices, found nostalgia and hauntology, although often based on exaggerated versions of real, or even fictitious, events or circumstances, produce outcomes that are real in their consequences; a conclusion absent from the works of Elias. Furthermore, I found not only the significance of nostalgia’s and hauntology’s role in this small village, but drew conclusions applicable to local, regional, national and worldwide relationships and spaces. Finally, my empirical contribution, by presenting and examining a single village as an empirical crucible, showed how nostalgia has helped the village develop from one that was considered undesirable, wicked, to one that is now, using the modern sense of the word, a ‘wicked’ or highly desirable place to live.</p
PremPath ethnographic interviews with staff
No full textThe PremPath study was funded by the National Institute for Health and Care Research Policy Research Programme (NIHR204242) between April 2023 and June 2025. The perinatal optimisation pathway brings together a number of evidence-based interventions to reduce the risk of neonatal death and associated preterm morbidities. This project was commissioned to examine how the pathway is working in practice. We aimed to explore how multiple clinical teams work together to make decisions about the optimisation and stabilisation of preterm infants and to explore the experiences of staff delivering the pathway, and parents and families receiving care. We took a qualitative approach: this resource comprises 29 ethnographic interviews staff from 4 Sites</p