Realising the Ambition - Being Me : National Practice Guidance for Early Years in Scotland

Since 2013 there has been a determined focus by the Scottish Government to work towards realising the ambition for Scotland to be the best place for children to grow up in and learn. Changes to the Children and Young People (Scotland) Act 2014, have resulted in our youngest children, particularly those from birth to starting school, being at the heart of significant new developments. In 2014 Scottish Government started to increase the number of hours of funded provision to 600 hours for 3 and 4 year olds and some two year olds. The national practice guidance, “Building the Ambition” was commissioned at this time to complement the new policy developments and to support practitioners. The further expansion of funded Early Learning and Childcare (ELC) to 1140 hours per year for all 3 and 4 year olds, and for around a quarter of 2 year olds will be available from August 2020. This expansion to 1140 hours seeks not only to extend funded places, but to also improve the quality of our ELC provision across Scotland. We know that the earliest years of life are crucial for every child. Evidence tells us that, if our early learning and childcare offer is to help children fulfil their potential and contribute to closing the poverty related gap in children’s outcomes, it has to be high quality. To support the expansion it was decided to refresh the original Building the Ambition, incorporating and updating relevant aspects of the Pre-Birth to Three guidance and extending across the child’s learning journey into the early years of primary school. This new guidance, Realising the Ambition: Being Me, reflects the original principles and philosophy of Building the Ambition and complements the current policy direction of ELC and early primary education. It aspires to support practitioners in delivering what babies and young children need most and how we can most effectively deliver this in Scotland to give children the best start in life. The practice guidance aims to support anyone who works with and for babies and young children across all areas of Scotland. It has been designed to: build confidence and capability of those who work with children and families from pre-birth to starting school and beyond; make links between practice, theory and policy guidance to reinforce aspects of high quality provision and the critical role practitioners play; clarify some aspects of current practice and provide a reference which practitioners can easily use; support improvement and quality by encouraging discussion, self reflection and questioning about relevant practice in each setting, and; provide advice on achieving the highest quality of ELC and early primary provision that will enable young children to experience and to play their own part in Scotland being the best place in the world to grow up

Patient-specific cancer genes contribute to recurrently perturbed pathways and establish therapeutic vulnerabilities in esophageal adenocarcinoma

Abstract: The identification of cancer-promoting genetic alterations is challenging particularly in highly unstable and heterogeneous cancers, such as esophageal adenocarcinoma (EAC). Here we describe a machine learning algorithm to identify cancer genes in individual patients considering all types of damaging alterations simultaneously. Analysing 261 EACs from the OCCAMS Consortium, we discover helper genes that, alongside well-known drivers, promote cancer. We confirm the robustness of our approach in 107 additional EACs. Unlike recurrent alterations of known drivers, these cancer helper genes are rare or patient-specific. However, they converge towards perturbations of well-known cancer processes. Recurrence of the same process perturbations, rather than individual genes, divides EACs into six clusters differing in their molecular and clinical features. Experimentally mimicking the alterations of predicted helper genes in cancer and pre-cancer cells validates their contribution to disease progression, while reverting their alterations reveals EAC acquired dependencies that can be exploited in therapy

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Disentangling oncogenic amplicons in esophageal adenocarcinoma

Esophageal adenocarcinoma is a prominent example of cancer characterized by frequent amplifications in oncogenes. However, the mechanisms leading to amplicons that involve breakage-fusion-bridge cycles and extrachromosomal DNA are poorly understood. Here, we use 710 esophageal adenocarcinoma cases with matched samples and patient-derived organoids to disentangle complex amplicons and their associated mechanisms. Short-read sequencing identifies ERBB2, MYC, MDM2, and HMGA2 as the most frequent oncogenes amplified in extrachromosomal DNAs. We resolve complex extrachromosomal DNA and breakage-fusion-bridge cycles amplicons by integrating of de-novo assemblies and DNA methylation in nine long-read sequenced cases. Complex amplicons shared between precancerous biopsy and late-stage tumor, an enrichment of putative enhancer elements and mobile element insertions are potential drivers of complex amplicons’ origin. We find that patient-derived organoids recapitulate extrachromosomal DNA observed in the primary tumors and single-cell DNA sequencing capture extrachromosomal DNA-driven clonal dynamics across passages. Prospectively, long-read and single-cell DNA sequencing technologies can lead to better prediction of clonal evolution in esophageal adenocarcinoma