DNA methylation-based classification of central nervous system tumours.

Accurate pathological diagnosis is crucial for optimal management of patients with cancer. For the approximately 100 known tumour types of the central nervous system, standardization of the diagnostic process has been shown to be particularly challenging-with substantial inter-observer variability in the histopathological diagnosis of many tumour types. Here we present a comprehensive approach for the DNA methylation-based classification of central nervous system tumours across all entities and age groups, and demonstrate its application in a routine diagnostic setting. We show that the availability of this method may have a substantial impact on diagnostic precision compared to standard methods, resulting in a change of diagnosis in up to 12% of prospective cases. For broader accessibility, we have designed a free online classifier tool, the use of which does not require any additional onsite data processing. Our results provide a blueprint for the generation of machine-learning-based tumour classifiers across other cancer entities, with the potential to fundamentally transform tumour pathology

Outcome after modern proton beam therapy in childhood craniopharyngioma: results of the prospective registry study KiProReg

Background Craniopharyngiomas (CPs) are rare tumours of the sellar region often leading to significant comorbidities due to their close proximity to critical structures. Aim of this study was to analyse survival outcome and late toxicities after surgery and proton beam therapy (PBT) in childhood CPs. Patients and methods Within the prospective XXXX study (XXXX), data of 74 childhood patients with CP, receiving PBT between 08/2013-06/2022 were eligible. Late toxicities were analysed according to the grading system of CTCAE 4.0. Results : Median follow-up (FU) since first diagnosis was 4.3 years (range, 0.8-14.7). 75.7% of patients received PBT at time of disease progression or recurrence, whereas 24.3% as part of their primary therapy (definitive or adjuvant). Predominantly (85.1%), pencil beam scanning technique was used. Median total dose and initial tumour volume were 5400 cGyRBE (relative biological effectiveness) and 17.64 cm³ (range, 3.07-300.59), respectively. The estimated (±SE) 3-year overall survival, progression-free and cystic failure-free survival rate after PBT were 98.2% (±1.7), 94.7% (±3.0), and 76.8% (±5.4), respectively. All local failures (n=3) were in-field relapses necessitating intervention and occurred exclusively in patients receiving PBT at progression or recurrence. Early cystic enlargements after PBT were typically asymptomatic and self-limiting. Fatigue, headaches, vision disorders, obesity and endocrinopathies were the predominant late toxicities. No high grade (≥3) new-onset visual impairment or cognitive deterioration occurred compared to baseline. The presence of cognitive impairments at the end of FU correlated with size of the planning target volume (p=0.034), Dmean dose to the temporal lobes (p=0.032,p=0.045) and the number of surgical interventions prior to PBT (p=0.029). Conclusions : Our findings demonstrate favourable local control rates using modern PBT with acceptable late toxicities. Cyst growth within 12 month after radiotherapy is typically not associated with tumour progression. Longer FU has to be awaited to confirm results

Examining Ecological Constraints on the Intergenerational Transmission of Attachment Via Individual Participant Data Meta-analysis

Parents\u2019 attachment representations and child\u2013parent attachment have been shown to be associated, but these associations vary across populations (Verhage et al., 2016). The current study examined whether ecological factors may explain variability in the strength of intergenerational transmission of attachment, using individual participant data (IPD) meta-analysis. Analyses on 4,396 parent\u2013child dyads (58 studies, child age 11\u201396 months) revealed a combined effect size of r =.29. IPD meta-analyses revealed that effect sizes for the transmission of autonomous-secure representations to secure attachments were weaker under risk conditions and weaker in adolescent parent\u2013child dyads, whereas transmission was stronger for older children. Findings support the ecological constraints hypothesis on attachment transmission. Implications for attachment theory and the use of IPD meta-analysis are discusse

Conceptual comparison of constructs as first step in data harmonization: Parental sensitivity, child temperament, and social support as illustrations

This article presents a strategy for the initial step of data harmonization in Individual Participant Data syntheses, i.e., making decisions as to which measures operationalize the constructs of interest - and which do not. This step is vital in the process of data harmonization, because a study can only be as good as its measures. If the construct validity of the measures is in question, study results are questionable as well. Our proposed strategy for data harmonization consists of three steps. First, a unitary construct is defined based on the existing literature, preferably on the theoretical framework surrounding the construct. Second, the various instruments used to measure the construct are evaluated as operationalizations of this construct, and retained or excluded based on this evaluation. Third, the scores of the included measures are recoded on the same metric. We illustrate the use of this method with three example constructs focal to the Collaboration on Attachment Transmission Synthesis (CATS) study: parental sensitivity, child temperament, and social support. This process description may aid researchers in their data pooling studies, filling a gap in the literature on the first step of data harmonization. • Data harmonization in studies using combined datasets is of vital importance for the validity of the study results. • We have developed and illustrated a strategy on how to define a unitary construct and evaluate whether instruments are operationalizations of this construct as the initial step in the harmonization process. • This strategy is a transferable and reproducible method to apply to the data harmonization process

Environmental and genetic influences on early attachment

Attachment theory predicts and subsequent empirical research has amply demonstrated that individual variations in patterns of early attachment behaviour are primarily influenced by differences in sensitive responsiveness of caregivers. However, meta-analyses have shown that parenting behaviour accounts for about one third of the variance in attachment security or disorganisation. The exclusively environmental explanation has been challenged by results demonstrating some, albeit inconclusive, evidence of the effect of infant temperament. In this paper, after reviewing briefly the well-demonstrated familial and wider environmental influences, the evidence is reviewed for genetic and gene-environment interaction effects on developing early attachment relationships. Studies investigating the interaction of genes of monoamine neurotransmission with parenting environment in the course of early relationship development suggest that children's differential susceptibility to the rearing environment depends partly on genetic differences. In addition to the overview of environmental and genetic contributions to infant attachment, and especially to disorganised attachment relevant to mental health issues, the few existing studies of gene-attachment interaction effects on development of childhood behavioural problems are also reviewed. A short account of the most important methodological problems to be overcome in molecular genetic studies of psychological and psychiatric phenotypes is also given. Finally, animal research focusing on brain-structural aspects related to early care and the new, conceptually important direction of studying environmental programming of early development through epigenetic modification of gene functioning is examined in brief

Attachment to mother and father at transition to middle childhood

The present study investigated concordance between representations of attachment to mother and attachment to father, and convergence between two narrative-based methods addressing these representations in middle childhood: the Manchester Child Attachment Story Task (MCAST) and the Secure Base Script Test (SBST). One hundred and twenty 6-year-old children were assessed by separate administrations of the MCAST for mother and father, respectively, and results showed concordance of representations of attachment to mother and attachment to father at age 6.5 years. 75 children were additionally tested about 12 months later, with the SBST, which assesses scripted knowledge of secure base (and safe haven), not differentiating between mother and father attachment rela- tionships. Concerning attachment to father, dichotomous classifications (MCAST) and a continuous dimension cap- turing scripted secure base knowledge (MCAST) converged with secure base scriptedness (SBST), yet we could not show the same pattern of convergence concerning attach- ment to mother. Results suggest some convergence between the two narrative methods of assessment of secure base script but also highlight complications when using the MCAST for measuring attachment to father in middle childhood

DNA methylation-based classification of central nervous system tumours.

Accurate pathological diagnosis is crucial for optimal management of patients with cancer. For the approximately 100 known tumour types of the central nervous system, standardization of the diagnostic process has been shown to be particularly challenging-with substantial inter-observer variability in the histopathological diagnosis of many tumour types. Here we present a comprehensive approach for the DNA methylation-based classification of central nervous system tumours across all entities and age groups, and demonstrate its application in a routine diagnostic setting. We show that the availability of this method may have a substantial impact on diagnostic precision compared to standard methods, resulting in a change of diagnosis in up to 12% of prospective cases. For broader accessibility, we have designed a free online classifier tool, the use of which does not require any additional onsite data processing. Our results provide a blueprint for the generation of machine-learning-based tumour classifiers across other cancer entities, with the potential to fundamentally transform tumour pathology

Global alliance for the promotion of physical activity : the Hamburg declaration

Non-communicable diseases (NCDs), including coronary heart disease, stroke, hypertension, type 2 diabetes, dementia, depression and cancers, are on the rise worldwide and are often associated with a lack of physical activity (PA). Globally, the levels of PA among individuals are below WHO recommendations. A lack of PA can increase morbidity and mortality, worsen the quality of life and increase the economic burden on individuals and society. In response to this trend, numerous organisations came together under one umbrella in Hamburg, Germany, in April 2021 and signed the ‘Hamburg Declaration’. This represented an international commitment to take all necessary actions to increase PA and improve the health of individuals to entire communities. Individuals and organisations are working together as the ‘Global Alliance for the Promotion of Physical Activity’ to drive long-term individual and population-wide behaviour change by collaborating with all stakeholders in the community: active hospitals, physical activity specialists, community services and healthcare providers, all achieving sustainable health goals for their patients/clients. The ‘Hamburg Declaration’ calls on national and international policymakers to take concrete action to promote daily PA and exercise at a population level and in healthcare settings.https://drc.bmj.com/am2024Sports MedicineSDG-03:Good heatlh and well-beingSDG-17:Partnerships for the goal