Improved Outcome for ALL by Prolonging Therapy for IKZF1 Deletion and Decreasing Therapy for Other Risk Groups

PURPOSE: The ALL10 protocol improved outcomes for children with ALL by stratifying and adapting therapy into three minimal residual disease-defined risk groups: standard risk, medium risk (MR), and high risk. IKZF1-deleted (IKZF1del) ALL in the largest MR group still showed poor outcome, in line with protocols worldwide, accounting for a high number of overall relapses. ALL10 showed high toxicity in Down syndrome (DS) and excellent outcome in ETV6::RUNX1 ALL. Poor prednisone responders (PPRs) were treated as high risk in ALL10. In ALL11, we prolonged therapy for IKZF1del from 2 to 3 years. We reduced therapy for DS by omitting anthracyclines completely, for ETV6::RUNX1 in intensification, and for PPR by treatment as MR. METHODS:Eight hundred nineteen patients with ALL (age, 1-18 years) were enrolled on ALL11 and stratified as in ALL10. Results were compared with those in ALL10. RESULTS: The five-year overall survival (OS), event-free survival (EFS), cumulative risk of relapse (CIR), and death in complete remission on ALL11 were 94.2% (SE, 0.9%), 89.0% (1.2), 8.2% (1.1), and 2.3% (0.6), respectively. Prolonged maintenance for IKZF1del MR improved 5-year CIR by 2.2-fold (10.8% v 23.4%; P = .035) and EFS (87.1% v 72.3%; P = .019). Landmark analysis at 2 years from diagnosis showed a 2.9-fold reduction of CIR (25.6%-8.8%; P = .008) and EFS improvement (74.4%-91.2%; P = .007). Reduced therapy did not abrogate 5-year outcome for ETV6::RUNX1 (EFS, 98.3%; OS, 99.4%), DS (EFS, 87.0%; OS, 87.0%), and PPR (EFS, 81.1%; OS, 94.9%). CONCLUSION: Children with IKZF1del ALL seem to benefit from prolonged maintenance therapy. Chemotherapy was successfully reduced for patients with ETV6::RUNX1, DS, and PPR ALL. It has to be noted that these results were obtained in a nonrandomized study using a historical control group.</p

A Functional Role for 4qA/B in the Structural Rearrangement of the 4q35 Region and in the Regulation of FRG1 and ANT1 in Facioscapulohumeral Dystrophy

The number of D4Z4 repeats in the subtelomeric region of chromosome 4q is strongly reduced in patients with Facio-Scapulo-Humeral Dystrophy (FSHD). We performed chromosome conformation capture (3C) analysis to document the interactions taking place among different 4q35 markers. We found that the reduced number of D4Z4 repeats in FSHD myoblasts was associated with a global alteration of the three-dimensional structure of the 4q35 region. Indeed, differently from normal myoblasts, the 4qA/B marker interacted directly with the promoters of the FRG1 and ANT1 genes in FSHD cells. Along with the presence of a newly identified transcriptional enhancer within the 4qA allele, our demonstration of an interaction occurring between chromosomal segments located megabases away on the same chromosome 4q allows to revisit the possible mechanisms leading to FSHD

xDelia: D18-2.4.2 Learning Intervention Package - Development and Evaluation (Year 3)

The core purpose of xDelia is to develop learning approaches to improve the financial decision making of private investors who trade frequently using a trading platform. This group has significant economic importance in the EU, and is sufficiently well understood to be a viable target of learning interventions. Much financial training has, to date, focused primarily on imparting propositional knowledge and increasing people’s understanding. However, investors may have appropriate knowledge, but despite this go on to be ruled by their attitudes, habits, or emotional states. Emotions mediate both rapid expert situation recognition and the application of expert intuition but also important persistent biases in decision-making such as framing effects and the disposition effect in particular. There is an increasing body of evidence that effective emotion regulation can reduce maladaptive biases mediated via emotions whilst still allowing the application of expert intuition. Investigating this, the project has developed new, technologically supported approaches to training; and the project has developed support for non-formal and informal learning in real-world trading settings to tackle the challenges faced by investors when they make financial decisions. This document sets out the nature and scope of the final xDelia learning pathway, its pedagogical underpinnings and constituent elements. A summary of major functionalities are described and learning applications. This document focuses on the evolution of the learning pathway in Year 3 of the xDelia Project and presents the final form of the learning pathway we have designed and its constituent elements. To be maximally useful to those wishing either to deploy the approaches and tools we have developed or to carry out further research and development, we also include a summary account of our evaluation of our learning approach1 and (in the appendices) documentation for each of the learning elements

xDelia: emotion-centred financial decision making and learning (final report)

Competence in financial matters has become part and parcel of everyday life, both at the work place and in our daily lives. Traditional learning cannot deliver the necessary skills, and more innovative solutions are needed. Serious games, wearable sensors, and a focus on emotions lie at the heart of this project’s novel, technology-supported approach to expertise and competence-building in financial decision making. xDelia is a 3-year pan-European project building on the knowledge, skills, and competences of seven partner organisations from a variety of research disciplines and from business. The principal objective of xDelia is to develop technology-enhanced learning approaches that help improve the financial decision making of investors who trade frequently using an electronic trading platform. We focus on emotions, and how they affect maladaptive decision biases and trading performance. Our earlier field work with traders has shown that the development of emotion regulation skills is a key facet of trader expertise. For that reason we consider expert traders our benchmark for adaptive behaviour rather than normative rationality. Our goal is to provide investors with the tools and techniques to develop greater self-awareness of internal states, increase their ability to reflect critically on emotion-informed choices, develop emotion management skills, and support the transfer of these skills to the real-world practice setting of financial trading. This report provides a comprehensive overview of what xDelia is about and what we have achieved over the life of the project. In the sections that follow, we explain the decision problems investors are faced with in a fast paced environment and the limitations of traditional approaches to reduce cognitive errors; introduce an alternative, technology-enhanced learning approach of diagnosis and feedback, skill development, and transfer; describe the learning intervention comprising twelve autonomous learning elements that we have developed; and present evidence from thirty-five studies we have conducted on learning effects and stakeholder acceptance. Much of this document is based on the thirty or so project deliverables, which offer far more detailed and definite discussion on the various aspects that we could only sketch out here. We have provided references to these deliverables throughout the document. The remainder of this report is divided into five sections: The xDelia project – summarises what xDelia tries to achieve, the learning intervention we have developed and the instruments we have used in the process, how the work unfolded over the three years, and how we evaluated our work and the project output. The concept and purpose of the learning intervention – describes the challenge of reducing and overcoming financial decision biases, and the alternative approach we have developed, the investor target group, and the pedagogy underpinning our learning intervention. The xDelia learning pathway – describes the pedagogical framework and the three stage learning approach of diagnosis and feedback, skill development, and learning transfer. Elements of the learning pathway – briefly describes the purpose and key features of each of the learning elements within the learning intervention. Evidence-based design and evaluation – presents an overview of the evaluation of the learning elements and of the user experience. For further details about xDelia, project publications and deliverables, and contacts, please visit the project web site at www.xdelia.org

DNA polymorphism and epigenetic marks modulate the affinity of a scaffold/matrix attachment region to the nuclear matrix

International audienc