An old spice with new tricks: Curcumin targets adenoma and colorectal cancer stem-like cells associated with poor survival outcomes.

The cost of cancer care globally is unsustainable and strategies to reduce the mounting burden of cancer are urgently needed. One approach is the use of preventive therapies to reduce cancer risk; dietary-derived compounds with good safety profiles represent a promising source of potential candidates but translating encouraging preclinical data to successful trials presents significant challenges. Development of curcumin, from the spice turmeric, as a preventive therapy for colorectal cancer (CRC) is hindered by poor understanding of its mechanism of action. Using patient derived xenografts and ex-vivo 3D-models exposed to clinically achievable curcumin concentrations, we found that it targets proliferating cancer stem-like cells (CSCs) within premalignant adenoma and early-stage cancer tissues, with broad spectrum activity across all molecular subtypes. Transcriptomics analysis revealed that curcumin pushes CSCs towards differentiation over self-renewal, thereby inhibiting tumour development. Evidence suggests these effects involve direct protein binding of curcumin to NANOG, a master regulator of CRC CSCs, and impairment of its transcriptional activity via direct interference with NANOG-DNA binding. Furthermore, curcumin decreased the proportion of proliferating CSCs, defined by NANOG/Ki67 co-expression in patient derived explants and individuals with tumours containing a small fraction of these cells had greatly improved progression-free survival compared to those in the highest quartile for expression. The use of curcumin to minimise this cellular population may yield significant benefit and its clinical evaluation is warranted. Overall, this study provides crucial mechanistic insight, identifying patient populations likely to benefit from curcumin for prevention of sporadic CRC and theragnostic biomarkers for assessing efficacy. [Abstract copyright: Copyright © 2025 The Authors. Published by Elsevier B.V. All rights reserved.

Germline transformation of the West Nile virus and avian malaria vector Culex quinquefasciatus Say using the piggyBac transposon system.

Culex quinquefasciatus Say is a mosquito which acts as a vector for numerous diseases including West Nile virus, lymphatic filariasis and avian malaria, over a broad geographical range. As the effectiveness of insecticidal mosquito control methods declines, the need has grown to develop genetic control methods to curb the spread of disease. The piggyBac transposon system - the most widely used genetic transformation tool in insects, including mosquitoes - generates quasi-random insertions of donor DNA into the host genome. However, despite the broad reported species range of piggyBac, previous attempts to use this tool to transform Culex quinquefasciatus mosquitoes have failed. Here we report the first successful transformation of Culex quinquefasciatus with the piggyBac transposon system. Using commercially synthesised piggyBac mRNA as a transposase source, we were able to generate three independent insertions of a ZsGreen fluorescent marker gene, with transformation efficiencies of up to 5 %. Through this work, we have expanded the genetic toolkit available for the genetic manipulation of Culex mosquitoes and thus removed a barrier to developing novel genetic control methods in this important disease vector. [Abstract copyright: Copyright © 2025. Published by Elsevier Ltd.

Physiotherapy for the Management of Polymyalgia Rheumatica: Results From a UK Cross‐Sectional Survey

Introduction: Polymyalgia rheumatica (PMR) international management guidelines advocate patient education and individualised exercises but lack evidence and physiotherapy practice for PMR is unknown. PMR is typically treated with glucocorticoids, but side effects are frequent and concerning to patients. This study investigated UK physiotherapy practice in PMR. Method: Physiotherapists recruited from UK rheumatology and physiotherapy professional networks and university alumni were invited to complete a postal or online questionnaire. Topics included experiences of managing PMR, perceived role and value of physiotherapy in PMR, assessment and management priorities and physiotherapists' education about PMR. Results were summarised using descriptive statistics. Results: 4288 invitations to participate were sent, and 1072 (25%) responses were received. Physiotherapy referrals for PMR were infrequent; 5.8% of respondents had treated ≥ 10 patients in the previous year. 80% of respondents advocated a physiotherapy role for PMR. 38% reported receiving some pre‐registration education about PMR within their qualifying physiotherapy programme. Establishing patients' knowledge and understanding of PMR, pain levels, and ability to undertake activities of daily living were physiotherapists' assessment priorities. 90% of respondents promoted self‐management approaches, including pacing and activity modification. Prioritising upper limbs, 89% prescribed individualised graded exercises to improve movement, muscle strength and activities of daily living function. Conclusion: A positive role for physiotherapy was reported for some people with PMR. Exercise, education and advice to improve daily functioning may be useful adjuncts to glucocorticoids. The limited PMR education for UK physiotherapists warrants attention. Further research is needed to evaluate the effectiveness of physiotherapy approaches for PMR

Trade unionism for England’s classroom teachers: the individual-collective division of responses to New Public Management’s decollectivisation of industrial relations

This dissertation explores teacher unions’ responses to decollectivisation and disaggregation generated through New Public Management in England’s schools. The research took place in a densely unionised public sector context with competitive multiunionism and fractured traditional collective bargaining. Decollectivisation and disaggregation are conceptualised as interwoven processes undermining trade unions’ capacity to develop or deploy countervailing collective power resources to neoliberal marketisation of education. Structural changes within the sector include academisation and the individualisation of rights at work. An overarching state project of reverse juridification multiplies individualised employment rights to deliver labour market flexibilities, and minimises, limits, or revokes collective employment rights to deliver labour market equity. Applying labour process theory in relation to the degradation via managerialism and performativity of teachers’ work, and actor-centred institutional theory to the broader political economy, the research applies lenses from the critical industrial relations perspective and radical legal research, adding the construct of trade union collective memory as a potential collective power resource. Through twenty-two semi-structured interviews with NASUWT and NEU respondents analysed thematically, their perceptions on how individual-collective division of issues occurs as they arise were interrogated. The study found the unions faced considerable decollectivising challenges. Foremost was misalignment of trade union and employer structures leading to a form of “workplace blindness” allied to a default individualisation of issue-handling. Contra that specific recollectivising tactics and evidence of novel legal mobilisation framed in terms of the right to justice for all teachers were found. The thesis contributes to knowledge of the challenges for and responses of workers and their unions in an under-researched sector at a time of conflict with the state and of change within the two unions involved

Investigating a structured diagnostic approach for chronic breathlessness in primary care: a mixed-methods feasibility cluster randomised controlled trial

Background: There is a need to reduce delays to diagnosis for chronic breathlessness to improve patient outcomes. Objective: To conduct a mixed-methods feasibility study of a larger cluster randomised controlled trial (cRCT) investigating a structured symptom-based diagnostic approach versus usual care for chronic breathlessness in primary care. Methods: 10 general practitioner practices were cluster randomised to a structured diagnostic approach for chronic breathlessness including early parallel investigations (intervention) or usual care. Adults over 40 years old at participating practices were eligible if presenting with chronic breathlessness without an existing explanatory diagnosis. The primary feasibility outcomes were participant recruitment and retention rate at 1 year. Secondary outcomes included number of investigations at 3 months, and investigations, diagnoses and patient-reported outcome measures (PROMs) at 1 year. Semistructured interviews were completed with patients and clinicians, and analysed using thematic analysis. Results: Recruitment rate was 32% (48/150): 65% female, mean (SD) age 66 (11) years, body mass index 31.2 kg/m2 (6.5), median (IQR) Medical Research Council dyspnoea 2 (2–3). Retention rate was 85% (41/48). At 3 months, the intervention group had a median (IQR) of 8 (7–9) investigations compared with 5 (3–6) investigations with usual care. 11/25 (44%) patients in the intervention group had coded diagnosis for breathlessness at 12 months compared with 6/23 (26%) with usual care. Potential improvements in symptom burden and quality of life were observed in the intervention group above usual care. Conclusions: A cRCT investigating a symptom-based diagnostic approach for chronic breathlessness is feasible in primary care showing potential for timely investigations and diagnoses, with PROMs potentially indicating patient-level benefit. A further refined fully powered cRCT with health economic analysis is needed

Learning from online hate speech and digital racism: From automated to diffractive methods in social media analysis

There has been a dramatic surge in uses of big data analytics and automated methods to detect and remove hate speech from social media, with these methods deployed both by platforms themselves and within academic research. At the same time, recent social scientific scholarship has accused social media data analytics of decontextualizing complex sociological issues and reducing them to linguistic problems that can be straightforwardly mapped and removed. Intervening in these debates, this article draws on findings from two interdisciplinary projects, spanning five years in total, which generated comparative datasets from Twitter (X). Focusing on three issues that we identified and negotiated in our own analysis – which we characterize as problems of context, classification and reproducibility – we build on existing critiques of automated methods, while also charting methodological pathways forward. Informed by theoretical debates in feminist science studies and STS, we set out a diffractive approach to engaging with large datasets from social media, which centralizes tensions rather than correlations between computational, quantitative and qualitative data

Benchmark stars for mean stellar density and surface gravity estimates of solar-type stars

Adding an independent estimate of the mean stellar density, , as a constraint in the analysis of stars that host transiting exoplanets can significantly improve the precision of the planet radius estimate in cases where the light curve is too noisy to yield an accurate value of the transit impact parameter, e.g. the light curves of Earth-size planets orbiting in the habitable zone of Sun-like stars that will be obtained by the PLAnetary Transits and Oscillations of stars (PLATO) mission. I have compiled a sample of 36 solar-type stars for which analysis of high-quality light curves together with constraints on the orbital eccentricity yield mean stellar density measurements with a median error of 2.3 per cent. Of these, 8 are in transiting exoplanet systems and 28 in eclipsing binary systems with very low mass companions that contribute <0.1 per cent of the total flux in the V band. A recalibrated empirical relation for stellar mass as a function of T, , and [Fe/H] has been used to find mass estimates with a typical precision of 5.2 per cent for the stars in this sample. Examples are given of how this sample can be used to test the accuracy and precision of and estimates from catalogues of stellar parameters for solar-type stars

Low-temperature growth of metal chalcogenide semiconductors

Metal chalcogenides exhibit a variety of intriguing properties and promising applications. However, a significant challenge in utilising these materials for electronic devices lies in producing high quality thin films. Chemical vapour deposition (CVD) is a scalable technique that can produce extraordinarily high-quality thin films which are nanometres in thickness, over large areas. High growth temperatures are often required in order to synthesise the best quality materials which hinder the use of CVD techniques for commercial thin film manufacture. This work centres on the development, optimisation and use of low-temperature CVD growth systems to grow metal chalcogenides films and two-dimensional materials utilising both aerosol-assisted chemical vapour deposition (AACVD) and salt-assisted chemical vapour deposition (SA-CVD), respectively. This enables film deposition to occur at lower temperatures when compared to existing reported traditional CVD methods, using single source dithiocarbamate precursors and halide salts. To synthesise metal sulfide, oxide and selenide semiconductors, that are suitable for a wide range of uses, such as optoelectronic, thermoelectric and catalytic applications. Thus, this could offer exciting opportunities for scalable renewable energy research by determining if low-temperature CVD methods can produce high quality films, that are comparable to their existing high temperature counterparts. In this project, materials morphology, crystal quality, lattice strain and structural composition were explored through various characterisation techniques, including Raman spectroscopy, X-ray diffraction (XRD) and X-ray photoelectron spectroscopy (XPS) and energy dispersive X-ray (EDX) analysis. The research has proven that low-temperature chemical vapour deposition methods can be utilized to produce high quality molybdenum, zinc and tin chalcogenide semiconductors, which are suitable for optoelectronic and thermoelectric devices and also show great promise for catalysing hydrogen evolution reactions. This mean we are one step closer to a highly efficient, low-cost clean energy future

Strategic Marketing Management

This practical textbook equips leaders and managers with the tools and insights they need to apply strategic marketing principles directly to their roles, driving business success and sustainable growth.Designed specifically for managers, MBA students, and senior executives across various industries—including healthcare, finance, engineering, and B2B—the book presents theory, actionable strategies and reflective exercises tailored to the challenges faced by professionals in non-marketing roles.Chapters delve into essential marketing concepts, such as market and customer insights, implementation of effective strategies, global marketing, brand management, and the impact of digital transformation. Real-world examples from leading companies like AstraZeneca, Bentley, and the NHS illustrate how strategic marketing principles can drive long-term growth, while reflective questions throughout the book encourage readers to apply these lessons to their own organizational challenges. Readers will learn how to:Make informed, data-driven decisions that align with business goalsDevelop and implement marketing strategies that are adaptable and future-focusedLead cross-functional teams to foster a customer-centric cultureLeverage emerging technologies and global trends to maintain a competitive edge.A valuable resource for students and leaders, this book will help you build the strategic marketing expertise needed to drive success in a rapidly changing landscape

How do credit ratings affect corporate investment efficiency?

This study examines the impact of credit ratings on the efficiency of firms' investments. Using a large sample of US firms, we find a positive relationship between the existence of credit ratings and investment efficiency. The cross-sectional analyses show the positive relationship is more pronounced for firms with greater information asymmetry and weaker corporate governance. Our results are robust to different methods to address potential endogeneity concerns, alternative measures of key variables, and the inclusion of additional control variables. Overall, the findings support the notion that credit rating agencies enhance information transparency and external monitoring, thereby allowing rated firms to promote investment efficiency. The findings contribute to our understanding of the significant role played by credit rating agencies in shaping firms' investment behaviour and efficiency