The MEGAPIE-TEST Project

The goals of the MEGAPIE initiative are to design, build and operate a 1MW heavy liquid metal target. The first step towards the realization of the MEGAPIE target was the feasibility studies, which outlined the entire project. Contextually to the feasibility studies the conceptual design phase started with the establishment of R&D working groups assisting the design and validation of both the target and its ancillary systems. In this framework the EU project MEGAPIE-TEST has been structured in three work packages with tasks concerning the finalization of the engineering design, the components and subsystem testing, the integral test and the first irradiation period. The MEGAPIE-TEST consortium is composed by the 14 partners: FZK, PSI, CEA, ENEA, SCK-CEN, CNRS /IDFE, IN2P3, LMPGM, EMN, ISMRA, UNIV-NANTES, U-PSUDXI, USTL. Currently the engineering design of the target has been finalized, its manufacturing has been launched and the design activities on the ancillary systems were almost completed. R&D activities in the fields of materials, thermal – hydraulics, structural mechanics, neutronic and nuclear assessment and liquid metal technologies were performed in order to assist specific design issues. Some Subsystem and component tests were also performed and the preparation of the integral test is an ongoing activity

Comparison of IgG diffusion and extracellular matrix composition in rhabdomyosarcomas grown in mice versus in vitro as spheroids reveals the role of host stromal cells

The tumour extracellular matrix acts as a barrier to the delivery of therapeutic agents. To test the hypothesis that extracellular matrix composition governs the penetration rate of macromolecules in tumour tissue, we measured the diffusion coefficient of nonspecific IgG in three rhabdomyosarcoma subclones growing as multicellular spheroids in vitro or as subcutaneous tumours in dorsal windows in vivo. In subcutaneous tumours, the diffusion coefficient decreased with increasing content of collagen and sulphated glycosaminoglycans. When grown as multicellular spheroids, no differences in either extracellular matrix composition or diffusion coefficient were found. Comparison of in vitro vs in vivo results suggests an over-riding role of host stromal cells in extracellular matrix production subjected to modulation by tumour cells. Penetration of therapeutic macromolecules through tumour extracellular matrix might thus be largely determined by the host organ. Hence, caution must be exercised in extrapolating drug penetrability from spheroids and multilayer cellular sandwiches consisting of only tumour cells to tumours in vivo

Inventory of current practices regarding hematopoietic stem cell transplantation in metachromatic leukodystrophy in Europe and neighboring countries

Background: For decades, early allogeneic stem cell transplantation (HSCT) has been used to slow neurological decline in metachromatic leukodystrophy (MLD). There is lack of consensus regarding who may benefit, and guidelines are lacking. Clinical practice relies on limited literature and expert opinions. The European Reference Network for Rare Neurological Diseases (ERN-RND) and the MLD initiative facilitate expert panels for treatment advice, but some countries are underrepresented. This study explores organizational and clinical HSCT practices for MLD in Europe and neighboring countries to enhance optimization and harmonization of cross-border MLD care. Methods: A web-based EUSurvey was distributed through the ERN-RND and the European Society for Blood and Marrow Transplantation Inborn Errors Working Party. Personal invitations were sent to 89 physicians (43 countries) with neurological/metabolic/hematological expertise. The results were analyzed and visualized using Microsoft Excel and IBM SPSS statistics. Results: Of the 30 countries represented by 42 respondents, 23 countries offer HSCT for MLD. The treatment is usually available in 1–3 centers per country (18/23, 78%). Most countries have no or very few MLD patients transplanted during the past 1–5 years. The eligibility criteria regarding MLD subtype, motor function, IQ, and MRI largely differ across countries. Conclusion: HSCT for MLD is available in most European countries, but uncertainties exist in Eastern and South-Eastern Europe. Applied eligibility criteria and management vary and may not align with the latest scientific insights, indicating physicians’ struggle in providing evidence-based care. Interaction between local physicians and international experts is crucial for adequate treatment decision-making and cross-border care in the rapidly changing MLD field

Assessment of motor functioning in the preschool period

The assessment of motor functioning in young children has become increasingly important in recent years with the acknowledgement that motor impairment is linked with cognitive, language, social and emotional difficulties. However, there is no one gold standard assessment tool to investigate motor ability in children. The aim of the current paper was to discuss the issues related to the assessment of motor ability in young pre-school children and to provide guidelines on the best approach for motor assessment. The paper discusses the maturational changes in brain development at the preschool level in relation to motor ability. Other issues include sex differences in motor ability at this young age, and evidence for this in relation to sociological versus biological influences. From the previous literature it is unclear what needs to be assessed in relation to motor functioning. Should the focus be underlying motor processes or movement skill assessment? Several key assessment tools are discussed that produce a general measure of motor performance followed by a description of tools that assess specific skills, such as fine and gross motor, ball and graphomotor skills. The paper concludes with recommendations on the best approach in assessing motor function in pre-school children

Newborn screening in metachromatic leukodystrophy – European consensus-based recommendations on clinical management

Introduction: Metachromatic leukodystrophy (MLD) is a rare autosomal recessive lysosomal storage disorder resulting from arylsulfatase A enzyme deficiency, leading to toxic sulfatide accumulation. As a result affected individuals exhibit progressive neurodegeneration. Treatments such as hematopoietic stem cell transplantation (HSCT) and gene therapy are effective when administered pre-symptomatically. Newborn screening (NBS) for MLD has recently been shown to be technically feasible and is indicated because of available treatment options. However, there is a lack of guidance on how to monitor and manage identified cases. This study aims to establish consensus among international experts in MLD and patient advocates on clinical management for NBS-identified MLD cases. Methods: A real-time Delphi procedure using eDELPHI software with 22 experts in MLD was performed. Questions, based on a literature review and workshops, were answered during a seven-week period. Three levels of consensus were defined: A) 100%, B) 75–99%, and C) 50–74% or >75% but >25% neutral votes. Recommendations were categorized by agreement level, from strongly recommended to suggested. Patient advocates participated in discussions and were involved in the final consensus. Results: The study presents 57 statements guiding clinical management of NBS-identified MLD patients. Key recommendations include timely communication by MLD experts with identified families, treating early-onset MLD with gene therapy and late-onset MLD with HSCT, as well as pre-treatment monitoring schemes. Specific knowledge gaps were identified, urging prioritized research for future evidence-based guidelines. Discussion: Consensus-based recommendations for NBS in MLD will enhance harmonized management and facilitate integration in national screening programs. Structured data collection and monitoring of screening programs are crucial for evidence generation and future guideline development. Involving patient representatives in the development of recommendations seems essential for NBS programs

The Entropy of Communication Turn Taking during a Collaborative Problem-Solving Task

Collaboration and teaming are critical for solving complex problems. However, little is known about how group dynamics affect teaming behaviours and, ultimately, problem-solving effectiveness. The present study aimed to validate a novel measure of the dynamics of team communication – here termed turn-taking entropy – and to investigate what aspects of those dynamics affect collaborative-problem-solving performance. Thirty-two teams of 4 were asked to complete a simulated crisis-response task in which they had to rank 15 items in order of their importance to their team’s survival (first individually and then as a team). Group responses were better than the aggregated individual responses of team members (suggesting teaming benefits), and were better when team members had task-relevant skills and knowledge. However, response quality was not significantly related to task completion time. Additionally, the proposed entropy measure appeared to capture group communication dynamics, and appeared to differentiate stable an unstable patterns of communication. Implications and directions for future research are discussed

Entwicklung einer Wiederaufbereitungsanlage fuer kontaminierte Boeden Abschlussbericht

SIGLEAvailable from TIB Hannover: F96B1373 / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekBundesministerium fuer Forschung und Technologie (BMFT), Bonn (Germany); Senatsverwaltung fuer Wissenschaft und Forschung, Berlin (Germany)DEGerman