5-Aminolevulinic acid (5-ALA) in paediatric brain tumour surgery—a systematic review and exploration of fluorophore alternatives

Purpose: Paediatric brain tumours represent the most common solid malignancies in children, with extent of resection being a critical prognostic factor. Fluorescence-guided surgery using 5-aminolevulinic acid (5-ALA) is well-established for adult high-grade gliomas, but its efficacy and safety in paediatric populations remain unclear. This systematic review evaluates the utility of 5-ALA fluorescence-guided surgery in paediatric brain tumours and explores alternative fluorophores. Methods: A systematic review was conducted according to PRISMA guidelines, analysing studies from MEDLINE and EMBASE published up to October 2024. Data on patient demographics, tumour fluorescence patterns, surgical outcomes, and adverse effects were extracted. Statistical analyses assessed fluorescence differences across tumour types and administration parameters. Results: Twenty-three studies, including 281 paediatric patients (mean age, 10 years), were analysed. The most common tumours included pilocytic astrocytomas (n = 45), medulloblastomas (n = 45), glioblastomas (n = 35), and ependymomas (n = 27). Strong fluorescence was observed more frequently in high-grade gliomas compared to low-grade gliomas (p &lt; 0.00001), non-glioma tumours (p &lt; 0.00001), and high-grade non-glioma tumours (p = 0.000485). Adverse effects were mostly transient; rare complications included transaminitis and dermatologic reactions. Conclusion: 5-ALA fluorescence-guided surgery shows promise in the resection of high-grade gliomas in paediatric patients, improving intraoperative visualisation. However, limited fluorescence in low-grade and non-glioma tumours underscores the need for tumour-specific approaches. Emerging alternatives, such as fluorescein sodium and tozuleristide, offer potential advantages. Future research should focus on optimising 5-ALA dosing, refining timing protocols, and conducting robust prospective trials to establish efficacy and safety in paediatric populations.</p

‘What else isn’t true?’, or, Dennis Kelly’s Expressionism

This chapter reads two plays by Dennis Kelly which opened in London in 2013: The Ritual Slaughter of Gorge Mastromas (first performed in the UK at the Royal Court, 5 September 2013) and Kelly’s ‘version’ of Georg Kaiser’s 1912 Expressionist play From Morning to Midnight, (in a production at the National Theatre, first performed 19 November 2013). While not claiming that Kelly ‘is’ an Expressionist playwright, I read these plays and productions alongside and against each other, suggesting that together they offer a chance to examine the politics of Expressionism and its legacies in contemporary British theatre. In clarifying Kelly’s relation to Expressionist theatre, I focus on a Nietzschean questioning of what is called morality. Nietzsche can be seen as the linking intellectual shadow behind both Kaiser’s Expressionism and the moral universe of The Ritual Slaughter. Both plays invite audiences to think through the complex relations of morality, truth and dramatic form

Intrauterine devices and gynaecological malignancies - an umbrella review of systematic reviews and meta-analyses

Background and aims: The intrauterine device (IUD) is globally recognised as a safe, cost-effective, and reliable contraceptive. This umbrella review and meta-analysis synthesises current evidence regarding the association between IUD usage and incidence of gynaecological and breast malignancies. Materials and methods: A comprehensive search of PubMed, Cochrane Library, and Ovid databases was conducted for systematic reviews and meta-analyses examining any type of IUD in relation to gynaecological and breast cancers. The screening and data extraction processes adhered to PRISMA guidelines, and random-effects meta-analysis was employed for data synthesis. Results: 323 titles and abstracts were screened, leading to the review of 41 full texts and the inclusion of 17 articles. Analyses of these articles and of their 32 primary sources indicated a decreased risk of cervical, endometrial and ovarian cancer for ever-users of IUD (respective OR: 0.63 [95% CI 0.48–0.82], 0.41 [0.31–0.54], and 0.71 [0.59–0.86]; all p &lt; 0.001). Our analysis did not yield any statistically significant association between IUD use and breast cancer risk (OR 1.00 [0.70–1.41], p = 0.99). Conclusion: IUD use is associated with a reduced risk of ovarian, endometrial, and cervical cancers, while no link was found with breast cancer. These findings can inform patient counselling on the benefits and risks of IUD use.</p

Effective healthcare communication with children and young people:a systematic review of barriers and facilitators

Objective: To identify children and young people's preferences for effective healthcare communication.Design: A systematic review of qualitative studies was conducted to identify evidence from children and young people on effective healthcare communication. Electronic databases and reference lists of relevant articles were searched to July 2020.Results: A total of 13 studies were included. Five major themes were identified: medical information (timing, amount, coordination and futures), person not patient (creating relationships, time, nurse involvement, sensitivity), type of communication (creative and interactive, behavioural, talking and listening, written communication), consultations (first impressions, with and without parents, actively promoting involvement, open and honest, age appropriate) and communication with parents (using parental knowledge, support).Conclusions: Research in this area remains sparse and consistent implementation is debateable. Children and young people articulate a preference for two-way healthcare communication. General principles for effective communication are identified as well as the need to avoid making assumptions and to tailor approaches to individuals. Establishing and maintaining relationships is essential and requires time and resources. Parents and carers have a positive role in healthcare communication which needs to be balanced with the needs and rights of children. All these factors also apply to children with communication difficulties or from marginalised groups, but additional extra support may be required.PROSPERO registration number: CRD42019145539.</p

Novel biomarkers in bone pathophysiology:Establishing reference intervals and biological variations estimates for serum leptin, sclerostin, lipocalin-2, osteoprotegerin, resistin and Dickkopf-related protein-1 from the European biological variation study (EuBIVAS) populations

A range of biomarkers of bone metabolism are thought to mediate adipose tissue-bone crosstalk and fulfil a homeostatic role. While considered clinically relevant, their utility and application appears limited by lack of data characterising biological variability and reference intervals rather than by analytical issues. We have therefore studied the biological variation (BV) of these biomarkers. Concentrations of Dikkopf-related protein 1, leptin, osteoprotegerin, sclerostin, lipocalin2 (Lcn2) and resistin were measured by Luminex assays in serum samples from the EuBIVAS study. Samples were taken once per week, over 10 consecutive weeks, from 91 subjects in cohorts from 5 European countries. Estimates of analytical variation (CVA), within-subject (CVI) and between-subject (CVG) BV were calculated and analytical imprecision (CVAPS) and analytical bias (BAPS) specifications, index of individuality (II), reference change values (RCV) for increase and decrease and the number of samples required to estimate the homeostatic set points (NHSPs) were derived. Mean concentrations differed between males and females for leptin, osteoprotegerin, and sclerostin, and for osteoprotegerin and sclerostin between females in fertile and menopausal ages. No male-to-female differences were observed in CVI estimates. Index of individuality was below 0.6, for all measurands. Determination of reference intervals (RI) limits indicated that all, with the exception Lcn2, described data which were non-gaussian distributed and that only leptin differed between sexes. Availability of high-quality biological variation enables objective assessment of the bone metabolism biomarker results which may enhance their clinical utility. The data indicates that they exhibit significant individuality.</p

Sandwich-structured GaIn(Zn)P/ZnSeS@ZnS quantum dots-ag@Fe3O4@SiO2 magnetoplasmonic nanosensor with simulation-driven design for influenza a(H1N1) virus biosensing

Developing next-generation ultrasensitive bioanalytical sensing systems requires multifunctional nanoarchitectures that integrate engineered photophysics with highly selective biorecognition interfaces. We report on a multifunctional, simulation-guided design of a fluorescence nanosensor for ultrasensitive detection of Influenza A (H1N1) virus in human saliva, integrating heavy-metal-free GaIn(Zn)P/ZnSeS@ZnS quantum dots (QDs) with magnetoplasmonic molecularly imprinted silica shell (Ag@Fe3O4@SiO₂-MIBs) interface. The QDs, engineered with a compositionally graded ZnSeS inner shell and ZnS outer shell, exhibit strong red emission (λemi = 652 nm) and high photoluminescence quantum yield (QY = 78 ± 1.4 %) in aqueous media following ligand exchange with thioglycolic acid (TGA). Self-consistent field (SCF) simulations revealed that TGA capping significantly stabilised the QDs surface and induced distinct magnetic properties, confirming favourable surface energetics for biosensing applications. The TGA-GaIn(Zn)P/ZnSeS@ZnS QDs were conjugated to H1N1-specific DNA aptamers and incorporated with graphene oxide (GO), forming a Förster resonance energy transfer (FRET)-based nanoprobe that switches from an “off” to “on” state upon viral recognition. Target-induced aptamer folding disrupted the QD-GO interaction, thereby restoring the QDs fluorescence. To amplify the fluorescence signal and enable selective enrichment, virus-imprinted Ag@Fe3O4@SiO₂-MIBs were employed. Finite-difference time-domain (FDTD) simulations demonstrated strong plasmon-exciton coupling between QDs and the Ag core, yielding approximately an 18-fold local field enhancement at a 5 nm spacing. The combined effect of molecular imprinting, magnetic separation, and plasmonic amplification enabled a detection limit of 0.15 pg/mL with high specificity against non-target viruses. This study presented a computationally guided design of hybrid nanomaterials for next-generation, point-of-care viral diagnostics with enhanced optical and molecular recognition performance

Role of artificial intelligence in data-centric additive manufacturing processes for biomedical applications

The role of additive manufacturing (AM) for healthcare applications is growing, particularly in the aspiration to meet subject-specific requirements. This article reviews the application of artificial intelligence (AI) to enhance pre-, during-, and post-AM processes to meet a wider range of subject-specific requirements of healthcare interventions. This article introduces common AM processes and AI tools, such as supervised learning, unsupervised learning, deep learning, and reinforcement learning. The role of AI in pre-processing is described in the core dimensions like structural design and image reconstruction, material design and formulations, and processing parameters. The role of AI in a printing process is described based on hardware specifications, printing configurations, and core operational parameters such as temperature. Likewise, the post-processing describes the role of AI for surface finishing, dimensional accuracy, curing processes, and a relationship between AM processes and bioactivity. The later sections provide detailed scientometric studies, thematic evaluation of the subject topic, and also reflect on AI ethics in AM for biomedical applications. This review article perceives AI as a robust and powerful tool for AM of biomedical products. From tissue engineering (TE) to prosthesis, lab-on-chip to organs-on-a-chip, and additive biofabrication for range of products; AI holds a high potential to screen desired process-property-performance relationships for resource-efficient pre- to post-AM cycle to develop high-quality healthcare products with enhanced subject-specific compliance specification

Managing masculinity when growing up with a violent father:A qualitative study of boys’ experiences

A limited qualitative literature explores children's lived experiences of violence; boys’ relationships with perpetrator fathers remain largely unexplored. Drawing on interviews with 31 boys, this paper explores the accounts of their relationships with their perpetrator fathers, focusing particularly on the implications of boys’ understanding of these relationships for their sense of burgeoning masculinity. Three themes are considered: in (a) relational ambiguity; (b) performing masculinities, managing violence; and (c) envisioning alternative futures and re-visioning the past. Our findings highlight the importance of interventions for boys that facilitate the expression of their often complex and ambivalent feelings and fears about their father's violence, and what it means for them and their future.</p

Human Rights in the Context of Climate Change:Emerging investment-related responsibilities in law and policy

This chapter examines the implications of human rights standards for investment activity in the context of climate change. It explores three key domains: the responsibility of businesses and investors for the human rights impacts of climate change, the role of climate change laws in regulating business and investment activities, and the ‘greening’ of human rights norms. These areas intersect to shape the responsibilities of investors in climate change mitigation. The chapter maps the evolution of these norms and their interaction, highlighting how they inform investment-related responsibilities, and delves into the implications of these evolving standards for investors. By examining these dimensions, the chapter provides insights into the emerging duties of investors within the framework of human rights and climate change