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#405 ICON8B:GCIG phase III randomised trial comparing first-line weekly dose-dense chemotherapy + bevacizumab to three-weekly chemotherapy + bevacizumab in high-risk stage III-IV epithelial ovarian cancer: final overall survival (OS) analysis
No full textIntroduction/Background: In ICON8B the use of dose-dense weekly paclitaxel (ddWT) with 3-weekly (q3w) carboplatin (C) and bevacizumab (BEV) as first-line treatment improved median progression-free survival (PFS) by 5.5 months (m) compared to standard q3w paclitaxel (T) dosing with C+BEV (22.2m vs 16.7m; Hazard Ratio (HR) 0.75, 95% CI 0.62-0.90 p=0.002). We now report the final overall survival (OS) analysis.Methodology: Eligible participants (pts) with high-risk stage III (residual disease >1cm diameter after immediate primary surgery (IPS) or requirement for primary chemotherapy) or stage IV EOC were randomised 1:1:1 to Arm B1 (standard- q3wC AUC5/6+q3wT 175mg/m2+ q3w BEV 7.5mg/kg); Arm B2- (q3wC AUC5/6+ddwT 80mg/m2); Arm B3- (q3wC AUC5/6+ddwT 80mg/m2+ q3wBEV 7.5mg/kg). Up to six cycles chemotherapy and 18 BEV cycles were administered. Arm B2 recruitment discontinued after ICON8 saw no evidence of PFS improvement with q3wCddwT vs q3wCT. OS was a key secondary outcome. Pts were followed for survival endpoints until trial closure on 18th Dec 2024.Results: From 07/2015 to 03/2020 579 pts were randomised to arms B1 + B3. Median age was 64 years; 91% had High Grade Serous Carcinoma; 93% Stage IIIc/IV; 84% primary chemotherapy with planned delayed primary surgery; 49% known germline BRCA1/2 mutation status. After median follow-up of 72.0m, 411 deaths were reported (197 B3; 214 B1). Median OS was 49.8m (95% CI 43·7-54.5m) in B3 and 39.6m (95% CI 34·7-45·0m) in B1 (HR 0·79, 95% CI 0·65-0·95, p=0·010). In pts receiving primary chemotherapy, median OS was 47.3m (95% CI 42.0-52.6m) in B3 and 37.1m (95% CI 32.3-42.1m) in B1.Conclusion: In pts with high-risk stage III-IV EOC, the use of ddwT in combination with q3w C + BEV as first-line systemic therapy improves median OS by 10.2m compared to q3w T dosing. ddwT with q3wC+BEV should now be considered a standard-of-care first-line treatment option in this group
Numerical and experimental investigation of void clogging removal in porous asphalt pavements
Get PDFPorous asphalt pavements are designed to drain water quickly, but their performance drops as sediment clogs the voids over time. This study investigates how clogging occurs and how different cleaning methods restore permeability, using CT scans, CFD-DEM simulations, and lab tests. Results show that clogging behaviour depends on particle size and source: gravity mainly affects particles under 2.36 mm, traffic pushes larger particles (up to 4.75 mm) deeper into the pavement, and rainfall carries fine particles below 1.18 mm into lower layers. High-pressure water jetting cleans more deeply than suction, restoring over 70% permeability, though it can drive particles further into the structure. The best cleaning was achieved by combining 20 MPa jetting with negative pressure suction. Cleaning performance did not improve significantly beyond 10 MPa, pointing to a pressure limit. Pavements with higher void ratios were easier to clean but more sensitive to damage. The results show that choosing the right cleaning method based on the pavement’s void ratio can improve results and reduce damage: 10 MPa water jetting works well for pavements with 15% void ratio, 20 MPa for 20%, and combining 20 MPa jetting with suction is best for 25%. The study contributes to optimizing maintenance protocols and extending the service life of permeable pavement systems in sustainable urban environments
Nicotine pouches, oral cancer and tobacco harm reduction:current evidence and research priorities
Get PDFTobacco smoking remains the most consistent and preventable risk factor for oral cancer, driven by exposure to combustion-derived toxins that promote DNA damage, inflammation and microbiota dysregulation. Global data show substantial geographic variability in disease burden, with particularly high incidence and mortality especially in South and Southeast Asia, where culturally reinforced and deeply embedded forms of high-nitrosamine smokeless tobacco and areca nut continue to drive risk. In this evolving landscape, nicotine pouches have rapidly expanded as tobacco-free oral products manufactured to deliver nicotine without combustion. Toxicological analyses reveal significantly lower levels of harmful constituents relative to cigarettes and traditional smokeless tobacco, and short-term clinical studies report reductions in oral mucosal irritation and gingival inflammation among exclusive users. However, no long-term epidemiological evidence is currently available to assess their potential impact upon oral carcinogenesis, and existing human studies remain few, small and heterogeneous. This mini review highlights critical priorities for research, including the need for long-term prospective studies, standardized product testing, independent toxicological assessments and surveillance of patterns of use, dual use and youth uptake. The integration of harm reduction approaches with established prevention strategies may offer opportunities to mitigate oral cancer risk in adults who smoke and/or consume unregulated smokeless tobacco products with high risk profiles that are very common in Asia, the Middle East and Africa. However, this approach requires cautious interpretation of the current evidence and ongoing monitoring of emerging products
Mothers’ experiences of formula feeding support in the UK:a qualitative systematic review
No full textPlaying with Privacy:Uncovering Everyday Judgments of Data Sensitivity Through an Arcade Machine Interface
No full textCurrent data protection legal frameworks, including the GDPR, classify “special” categories of personal data that are deemed deserving of higher protection due to their impact on fundamental rights. Yet, these legal abstractions fail to capture how individuals themselves judge sensitivity in everyday digital contexts. This disconnect may undermine intelligibility and erode trust in data protection as a legal institution. Despite its centrality to privacy protection, limited empirical work has systematically compared public sensitivity judgments against the special categories of protected data under Article 9 GDPR. We address this gap through a mixed-methods design that integrates nine semi-structured interviews with a game-like survey deployed on public arcade machines. This approach generated 2,935 responses from 224 participants enabling in-situ analysis of everyday judgments. By operationalising an ontology capturing who collects data, what data are collected, and for what purpose, we systematically compared responses across demographic groups. Contrary to literature assumptions that health and financial data are primary markers of data sensitivity, our findings demonstrate that expressive content, messages, photos, and social ties elicited the strongest resistance to sharing by citizens. Acceptance was shaped decisively by purpose. Citizens tolerated safety and functionality, whilst advertising and vague claims of “research” were rejected. Attitudes varied systematically, with women disproportionately resistant to sharing expressive content, and higher education and digital literacy predicting greater caution. This study demonstrates that data sensitivity cannot be reduced to fixed legal categories. Rather, it is socially situated and purpose-dependent. Our findings provide empirical foundations for reimagining consent flows, privacy defaults, and transparency mechanisms that align with everyday logics. This can enable the development of systems that people can genuinely understand, trust, and consent to
Effects of Advanced Trauma Life Support® training compared with standard care on adult trauma patient outcomes (ADVANCE TRAUMA):study protocol for a stepped-wedge cluster randomised trial
Get PDFBackground: Advanced Trauma Life Support® (ATLS®) is the most widely adopted form of trauma life support training worldwide, but there is no high-quality evidence that it can improve patient outcomes. The aim of this trial is to compare the effects of ATLS® training with standard care on outcomes in adult trauma patients. Methods: ADVANCE TRAUMA is a batched stepped-wedge cluster randomised controlled trial in India, where ATLS® is not routinely implemented. The trial will be conducted in 30 clusters (hospitals), organised into six batches of five clusters each. All clusters transition through three phases: first, a standard care phase; second, a 1-month transition phase, during which the training is delivered; and finally, an intervention phase, for a total of 13 months. Each cluster is randomised to an implementation sequence that defines the duration of the standard care and intervention phases. The trial will include at least 4320 adult trauma patients (≥ 15 years) who present to emergency departments and are subsequently admitted or transferred for admission. The primary outcome is in-hospital mortality within 30 days of arrival at the emergency department. Discussion: This will be the first large-scale trial to provide robust evidence of the effectiveness of ATLS® since the programme was initiated in 1978. Regardless of the findings, this study will have important implications for trauma life support training globally. If ATLS® training improves patient outcomes, ways to promote its use and optimise its implementation, especially in low- and middle-income countries such as India, should be explored. If patient outcomes do not improve, trauma life support training must change. Trial registration: Clinical Trials Registry–India (CTRI/2024/07/071336), ClinicalTrials.gov (NCT06321419, first registered 2024–03–20)
Existing research guidelines for inclusive trials methodology. Working toward the integration of qualitative research, equity, diversity, and inclusion and trials methodology:a focused mapping review
Get PDFBackgroundEquity, diversity, and inclusion (EDI) are increasingly emphasized in clinical research, yet practical guidance for applying inclusion principles across all clinical trial stages remain limited. Qualitative research can help address this gap by exploring participant experiences and identifying barriers to inclusive trial conduct. The aim of this review is to map guidelines and recommendations in relation to inclusive trials methodology and to identify areas across these resources that can be potentially informed by qualitative research. This review presents Phases 1 and 2 of the QuAlitative reSearch Supporting IncluSive Trials (Q-ASSIST) study.MethodsIn Phase 1, we conducted a focused mapping review and synthesis (FMRS) of publicly available guidelines related to Phase 3 and later clinical trials involving human participants. Eligible guidelines included those offering recommendations to enhance inclusive trial design and conduct. Each guideline was mapped to a priori data extraction framework informed by the Standard Protocol Items: Recommendations for Interventional Trials and Consolidated Standards of Reporting Trials 2025 guidelines. We then performed a narrative synthesis to examine the EDI focus of the selected guidelines and structured the findings according to the PRO-EDI Framework. In Phase 2, we juxtaposed the trial stages identified through our FMRS with O'Cathain et al’s framework of qualitative research in trials.ResultsWe identified 15 guidelines through FMRS. Through conceptual mapping to Standard Protocol Items: Recommendations for Interventional Trials and Consolidated Standards of Reporting Trials headings, we developed a 12-stage trial lifecycle framework (the Q-ASSIST trial stages model) to organize inclusion guidance. Most guidelines emphasized early stages of trials, with later stages less frequently addressed. Mapping to the PRO-EDI framework showed strong attention to race/ethnicity, gender, socioeconomic status, and disability, but limited focus on sexual identity, education, or intersectionality. Juxtaposition with O'Cathain et al’s framework highlighted similar gaps in how qualitative research has been used, especially in later trial stages.ConclusionCurrent inclusion guidance is concentrated in the early stages of trial design, with limited attention to later trial stages. Qualitative research offers a valuable way to address these gaps by capturing participant perspectives and supporting inclusive practices across the trial lifecycle. This review provides a foundation for developing practical tools to guide more inclusive trials, with the next phase involving coproduction of guiding principles with interest holders
Decentralized Cooperative Localization for Multi-Robot Systems with Asynchronous Sensor Fusion
Get PDFDecentralized cooperative localization (DCL) is a promising approach for nonholonomic mobile robots operating in GPS-denied environments with limited communication infrastructure. This paper presents a DCL framework in which each robot performs localization locally using an Extended Kalman Filter, while sharing measurement information during update stages only when communication links are available and companion robots are successfully detected by LiDAR. The framework preserves cross-correlation consistency among robot state estimates while handling asynchronous sensor data with heterogeneous sampling rates and accommodating accelerations during dynamic maneuvers. Unlike methods that require pre-aligned coordinate systems, the proposed approach allows robots to initialize with arbitrary reference-frame orientations and achieves automatic alignment through transformation matrices in both the prediction and update stages. To improve robustness in feature-sparse environments, we introduce a dual-landmark evaluation framework that exploits both static environmental features and mobile robots as dynamic landmarks. The proposed framework enables reliable detection and feature extraction during sharp turns, while prediction accuracy is improved through information sharing from mutual observations. Experimental results in both Gazebo simulation and real-world basement environments show that DCL outperforms centralized cooperative localization (CCL), achieving a 34% reduction in RMSE, while the dual-landmark variant yields an improvement of 56%. These results demonstrate the applicability of DCL to challenging domains such as enclosed spaces, underwater environments, and feature-sparse terrains where conventional localization methods are ineffective
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