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CONSORT–Children and Adolescents (CONSORT-C) 2026 Extension Statement: Enhancing the Reporting and Impact of Pediatric Randomized Trials
Get PDFImportance Randomized controlled trials (RCTs) in children and adolescents provide evidence for patients, families, researchers, clinicians, regulators, funders, policymakers, and other interest holders to inform decisions about health care interventions and improve outcomes for young patients and their families. To critically evaluate, interpret, and apply trial results, readers require access to a complete and transparent report of what was planned, done, and found, taking unique considerations specific to children and adolescents into account. Harmonized guidance based on evidence and consensus is needed to optimize standardized reporting and reduce research waste in pediatric RCTs.Objective To develop a pediatric reporting guideline extension to the Consolidated Standards of Reporting Trials (CONSORT) 2025 guideline, CONSORT–Children and Adolescents (CONSORT-C) 2026, that supports comprehensive reporting and enhances the transparency, reproducibility, accuracy, and utility of published pediatric RCT reports.Evidence Review The Enhancing the Quality of Transparency of Health Research (EQUATOR) Network’s published framework primarily informed the development of CONSORT-C 2026. A literature review was conducted to generate a list of candidate reporting items. To obtain direct input from young people and family caregivers throughout the project, a Youth Advisory Group and a Family Caregiver Advisory Group were formed. An international Delphi study with a priori consensus thresholds, consensus meeting, group writing of the explanation and elaboration paper, and pilot testing were conducted.Main Outcomes and Measures Harmonized guidance based on evidence and consensus is needed to optimize standardized reporting and reduce research waste in pediatric RCTs. As an extension to the CONSORT 2025 statement, the CONSORT-C 2026 reporting guideline aims to improve the quality and completeness of reporting of pediatric RCTs that involve participants aged 0 to 19 years.Findings The new CONSORT-C 2026 guideline is an extension to the updated CONSORT 2025 statement and adds reporting items applicable to pediatric RCT reports involving children and adolescents aged 0 to 19 years. Developed in partnership with young people (aged 10-24 years) and family caregivers, CONSORT-C 2026 comprises 13 new items recommended to be reported in pediatric RCT reports in addition to the CONSORT 2025 items. The 13 new reporting items include 1 youth-generated and 6 youth-endorsed items. CONSORT-C 2026 can be considered a minimum set of reporting items applicable to pediatric RCT reports reflecting the priorities of clinicians, researchers, young people, family caregivers, and other interest holders.Conclusions and Relevance Widespread implementation and uptake of CONSORT-C 2026 should optimize the usability of trial results for these populations, improve the reproducibility of trial results, and reduce research waste
SPIRIT-C 2026 explanation and elaboration: recommendations for enhancing the reporting and usefulness of paediatric randomised trial protocols
Get PDF•A well written protocol for paediatric randomised controlled trials (RCT) is critical for the evaluation of the aim, design, implementation, measurement, planned analyses, and participant burden and safety of trials that evaluate interventions for newborns, infants, children, and adolescents•An extension to the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) 2025 statement, SPIRIT-Children and Adolescents (SPIRIT-C) 2026, comprises 17 essential reporting items for paediatric RCT protocols, and was developed simultaneously with the Consolidated Standards of Reporting Trials (CONSORT) statement for paediatric RCT reports (CONSORT-C 2026)•This explanation and elaboration paper provides users with essential context for the newly developed SPIRIT-C 2026 items, and guidance on how to report these details in a paediatric RCT protocol•This pedagogical paper serves as a resource to facilitate the development of comprehensive, transparent, high quality paediatric RCT protocols that are useful to candidate trial participants, funders, ethics boards, trial registries, regulators, systematic reviewers, journal editors, peer reviewers, and paediatric researcher
Unpacking adaptation lock-ins: Explaining the persistence of the adaptation gap
Get PDFClimate change adaptation is increasingly outpaced by accelerating climate risks, resulting in a persistent and widening adaptation gap. Many current interventions remain incremental and insufficient, failing to address the scale of transformation required. We argue that this shortfall is best understood through the concept of adaptation lock-ins—systemic constraints that both cause and result from maladaptation. These lock-ins generate self-reinforcing dynamics that trap institutions and policy systems in established trajectories, hindering more ambitious and forward-looking action. In this paper, we explore how a deeper understanding of lock-ins can help explain enduring adaptation deficits and structural barriers to sustainable change. We also discuss methodological approaches to identifying lock-in mechanisms and show how such insights can be mobilized to inform deliberate ‘unlocking’ strategies that enable more equitable and transformative adaptation pathways and sustainability transformations
m6A RNA Methylation Is Increased in Tumour Invasive Regions and Influences Invasive Capability and Chemotherapeutic Sensitivity in Adult Glioblastoma
Get PDFAdult glioblastoma multiforme (GBM) is the most common primary malignant brain tumour caused by multiple molecular factors. N6-methyl-adenosine (m6A) is an abundant RNA modification that governs cellular RNA metabolism. We hypothesise that changes in m6A-modified RNA and regulatory machinery such as the writer proteins, Methyltransferase 3 (METTL3) and WT1-associating protein (WTAP), the demethyltransferase protein, and Alpha-ketoglutarate dependent dioxygenase (FTO), are driving factors of GBM development and treatment resistance. Here, we investigated m6A-RNA spatial and quantitative abundance and expression of m6A effector proteins directly in GBM tissue and patient-derived low-passage primary adult GBM and low-grade glioma (LGG) cells, and explored the consequences of m6A-RNA disruption on GBM invasive capabilities, self-renewal and responsiveness to temozolomide (TMZ). We observed that METTL3, WTAP and FTO transcript and protein expression were significantly increased in cells derived from invasive regions of GBM tumours, and elevated WTAP and FTO expression significantly correlated with poor GBM patient survival. We further found that the abundance of m6A-modified RNA in GBM tumours was significant higher in rim and invasive tissue, as well as significantly higher in patient-derived cells from GBM tumour invasive regions. Functional depletion of these effector proteins significantly altered m6A levels on and the expression of the pluripotency stem cell marker SOX2 while also impairing self-renewal and cell invasion behaviour and increasing sensitivity to TMZ. The targeting of RNA modification regulatory mechanisms reveals novel therapeutic strategies aimed at improving clinical outcomes for GBM patients
Rapid transfer to specialist orthopaedic ward reduces mortality in hip fracture patients, but several factors reduce the ability to achieve the < 4-hour target
Get PDFPurpose: Hip fractures are one of the most common fracture types in adults. Rapid admission to orthopaedic wards from ED ( 4h), and then by 30-day mortality. Logistic regression analyses were performed to identify factors associated with delayed admission to specialist wards and to assess the independent effect of admission delay (over 4h) on 30-day mortality. Results: Out of 5937 patients for whom admission data were available, 19% (1131/5937) were admitted within 4h. Results showed that lower AMT score (OR 0.98, 95% CI: 0.96-1.00, p = 0.014), out-of-hours presentation (OR 1.27, 95% CI: 1.11–1.45, p < 0.001), and a higher Charlson Comorbidity Index (OR 1.05, 95% CI: 1.02–1.09, p = 0.003) were associated with an increased chance of admission delays exceeding 4h. Furthermore, admission delays of more than 4h (OR 1.44, 95% CI: 1.06–1.95, p = 0.02) were associated with increased 30-day mortality, controlling for the other risk factors. Conclusion: Timely admission of hip fracture patients over the age of 60 is critical to reduce 30-day mortality. Low AMT score, out-of-hours presentation, and multiple comorbidities impact the timeliness of admissions in our hospital, highlighting a need to address these factors to improve care for this population
Maximum residual strong monogamy inequality for multiqubit entanglement
Get PDFWe establish two inequalities, the weighted strong monogamy (WSM) and the maximum residual strong monogamy (MRSM), which sharpen the generalized Coffman-Kundu-Wootters inequality for multiqubit states. The WSM inequality distinguishes itself from the strong monogamy (SM) conjecture [B. Regula et al., Phys. Rev. Lett. 113, 110501 (2014)] by using coefficients rather than exponents to modulate the weight allocated to various -partite contributions. In contrast, the MRSM inequality is formulated using only the maximum -partite entanglement. We find that the residual entanglement of the MRSM inequality can effectively distinguish the separable states. We also compare the tightness of various SM inequalities and provide examples using a four-qubit mixed state and a five-qubit pure state to illustrate the MRSM inequality. These examples characterize the trade-off relations among entanglement components involving varying numbers of qubits. Our results provide a rigorous framework to characterize and quantify the monogamy of multipartite entanglement
Dynamics of AGN feedback in the X-ray bright East and Southwest 'arms' of M87, mapped by XRISM
No full textContext. AGN feedback plays a critical role in regulating gas cooling and star formation in massive galaxies and at the centres of galaxy clusters. As the central galaxy in the nearest cluster, M87 provides the best spatial resolution for disentangling the complex interactions between AGN jets and the surrounding environment. Aims. We investigate the velocity structure of the multitemperature X-ray gas in M87, particularly in the eastern and southwestern arms associated with past AGN outbursts, using high-resolution spectroscopy from XRISM/Resolve. Methods. We analyze a mosaic of XRISM/Resolve observations covering the core of M87, fitting single-and multi-temperature models to spectra extracted from different regions and energy bands. We assess the line-of-sight velocities and velocity dispersions of the hotter ambient and cooler uplifted gas phases, and evaluate systematic uncertainties related to instrumental gain calibration. Results. The hotter ICM phase, traced by Fe He-α emission, shows velocity dispersions below ∼ 100 km/s, and no significant velocity shifts between the arms and a relaxed offset region, suggesting limited dynamical impact from older AGN lobes. In contrast, the cooler gas phase appears to exhibit larger line of sight velocity gradients up to several hundred km/s as well as a higher velocity dispersion than the ambient hot phase, although these conclusions remain tentative pending improvements in the robustness of the gain calibration at lower energies. Conclusions. The first microcalorimeter-resolved map of gas dynamics in M87 supports the uplift scenario for the X-ray arms, with the cooler gas in the east and southwest seemingly moving in opposite directions along the line of sight. The kinetic energy is a small fraction of the gravitational potential energy associated with the gas uplift, and XRISM further suggests that AGN-driven motions may be short-lived in the hot ambient ICM. These constraints provide important input towards shaping future models of AGN feedback
A UK perspective on responsible education for responsible AI: a multidisciplinary review and evaluation framework
Get PDFResponsible Artificial Intelligence (RAI) education has emerged as a way of approaching the field of AI to address a host of concerns (Bentley et al., 2023). Many education providers have been releasing new RAI-related online courses, programmes, or toolkits. When combined with the issues emerging from the development, deployment, and use of AI, the expansion of RAI education and the proliferation of resources raise two critical questions. First, what can we learn about RAI from examining both the content and structure of publicly available RAI educational resources? Second, how might we understand the quality and impact of these RAI resources? We conducted a systematic search of UK RAI educational resources found online. We first present a descriptive analysis of 211 resources collected, including their type, format, cost, sector, audience, and type of provider. Furthermore, we describe our collaborative approach to analysing four pre-selected resources in-depth, from which we outlined an evaluation framework that we then employed for assessing the content of a subset of 47 resources. The five crucial areas of our framework could guide both learners and developers when approaching RAI resources
Health economic model to evaluate the cost-effectiveness of smoking cessation services integrated within lung cancer screening in the United Kingdom
Get PDFIntroduction: Integrating smoking cessation supports into lung cancer screening can improve abstinence rates. However, healthcare decision-makers need evidence of cost-effectiveness to understand the cost/benefit of adopting this approach.Methods: To evaluate the cost-effectiveness of smoking cessation interventions, and service delivery, we used a cohort-based Markov model, adapted from previous National Institute for Health and Care Excellence (NICE) guidelines on smoking cessation. This uses long-term epidemiological data to capture the prevalence of the smoking-related illnesses, updated through targeted literature searches as required from the core NICE model, with costs extracted from publicly recognised UK sources.Results: All smoking cessation interventions appeared cost-effective at a threshold of £20 000 per quality-adjusted life year, compared with no intervention or behavioural support alone. Offering immediate smoking cessation as part of lung cancer screening appointments, compared with usual care (onward referral to stop smoking services), was also estimated to be cost-effective with a net monetary benefit of £2198 per person, and a saving of between £34 and £79 per person in reduced workplace absenteeism among working age attendees. Estimated healthcare cost savings were more than four times greater in the most deprived quintile compared with the least deprived, alongside a fivefold increase in quality adjusted life years accrued.Conclusions: Smoking cessation interventions within lung cancer screening are cost-effective and should be integrated, so that treatment is initiated during screening visits. This is likely to reduce overall costs to the health service, and wider integrated care systems, improve quality and length of life, and may lessen health inequalities
Experimental study on thermal characteristics of a state of art hairpin winding permanent magnet motor for automotive applications
Get PDFThis study investigates the thermal characteristics of the end-windings of a state-of-the-art hairpin winding permanent magnet motor designed for automotive applications. Hairpin windings offer advantages in terms of higher fill factors and automated manufacturing processes, making them ideal for high-performance motors. Water jacket cooling is used in the present study as it is one of the cost-efficient, reliable and commonly used techniques for mass-production. The experiments are conducted over a wide range of Reynolds numbers (ReDH = 425–3610) covering a typical range of flow rates used in automotive industries. The influence of coolant fluid properties on the thermal characteristics of end-windings is investigated by varying Prandtl number (Pr = 12.5 to 91). The results demonstrate that cooling characteristics are strongly influenced by gravitational forces. A distinct pattern of heat transfer is noticed for co-current (where gravity and flow direction are same) and counter-current direction (where gravity opposes the flow direction). This leads to variation in the heat transfer in the circumferential direction. A due consideration of the gravitational forces while designing the water jacket can minimize these thermal gradients. Heat transfer increases with the increment in the flow Reynolds number but rate of increment is higher towards the lower Reynolds number. Fluid properties have a significant influence on the heat transfer characteristics. A higher thermal diffusivity fluid leads to better heat transfer despite the higher Prandtl number
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