Towards a more functional and dynamic assessment of children with special needs in function of more inclusive education

Towards a more functional and dynamic assessment of children with special needs in function of more inclusive education - We present the Guidelines for Inclusive Assessment of children that experiment Special Educational Needs, developed by the DAFFODIL project team

Lumping procedure for a kinetic model of catalytic naphtha reforming

A lumping procedure is developed for obtaining kinetic and thermodynamic parameters of catalytic naphtha reforming. All kinetic and deactivation parameters are estimated from industrial data and thermodynamic parameters are calculated from derived mathematical expressions. The proposed model contains 17 lumps that include the C6 to C8+ hydrocarbon range and 15 reaction pathways. Hougen-Watson Langmuir-Hinshelwood type reaction rate expressions are used for kinetic simulation of catalytic reactions. The kinetic parameters are benchmarked with several sets of plant data and estimated by the SQP optimization method. After calculation of deactivation and kinetic parameters, plant data are compared with model predictions and only minor deviations between experimental and calculated data are generally observed

Cross-talk between GLI transcription factors and FOXC1 promotes T-cell acute lymphoblastic leukemia dissemination

T-cell acute lymphoblastic leukemia (T-ALL) is a highly malignant pediatric leukemia, where few therapeutic options are available for patients which relapse. We find that therapeutic targeting of GLI transcription factors by GANT-61 is particularly effective against NOTCH1 unmutated T-ALL cells. Investigation of the functional role of GLI1 disclosed that it contributes to T-ALL cell proliferation, survival, and dissemination through the modulation of AKT and CXCR4 signaling pathways. Decreased CXCR4 signaling following GLI1 inactivation was found to be prevalently due to post-transcriptional mechanisms including altered serine 339 CXCR4 phosphorylation and cortactin levels. We also identify a novel cross-talk between GLI transcription factors and FOXC1. Indeed, GLI factors can activate the expression of FOXC1 which is able to stabilize GLI1/2 protein levels through attenuation of their ubiquitination. Further, we find that prolonged GLI1 deficiency has a double-edged role in T-ALL progression favoring disease dissemination through the activation of a putative AKT/FOXC1/GLI2 axis. These findings have clinical significance as T-ALL patients with extensive central nervous system dissemination show low GLI1 transcript levels. Further, T-ALL patients having a GLI2-based Hedgehog activation signature are associated with poor survival. Together, these findings support a rationale for targeting the FOXC1/AKT axis to prevent GLI-dependent oncogenic Hedgehog signaling

The spleen as a sanctuary site for residual leukemic cells following ABT-199 monotherapy in ETP-ALL.

B-cell lymphoma 2 (BCL-2) has recently emerged as a therapeutic target for early T-cell progenitor acute lymphoblastic leukemia (ETP-ALL), a high-risk subtype of human T-cell ALL. The major clinical challenge with targeted therapeutics, such as the BCL-2 inhibitor ABT-199, is the development of acquired resistance. We assessed the in vivo response of luciferase-positive LOUCY cells to ABT-199 monotherapy and observed specific residual disease in the splenic microenvironment. Of note, these results were confirmed by using a primary ETP-ALL patient-derived xenograft. Splenomegaly has previously been associated with poor prognosis in diverse types of leukemia. However, the exact mechanism by which the splenic microenvironment alters responses to specific targeted therapies remains largely unexplored. We show that residual LOUCY cells isolated from the spleen microenvironment displayed reduced BCL-2 dependence, which was accompanied by decreased BCL-2 expression levels. Notably, this phenotype of reduced BCL-2 dependence could be recapitulated by using human splenic fibroblast coculture experiments and was confirmed in an in vitro chronic ABT-199 resistance model of LOUCY. Finally, single-cell RNA-sequencing was used to show that ABT-199 triggers transcriptional changes in T-cell differentiation genes in leukemic cells obtained from the spleen microenvironment. Of note, increased expression of CD1a and sCD3 was also observed in ABT199-resistant LOUCY clones, further reinforcing the idea that a more differentiated leukemic population might display decreased sensitivity toward BCL-2 inhibition. Overall, our data reveal the spleen as a site of residual disease for ABT-199 treatment in ETP-ALL and provide evidence for plasticity in T-cell differentiation as a mechanism of therapy resistance

Management of burn wounds of the head and neck region

Management of the severely burned patient is very often a challenge, not only due to major disturbances in anatomy and physiological processes, but also because the relatively low incidence of this pathology in both civilian and military practice results in care providers' lack of experience. The purpose of this educational document is to provide doctors confronted with these formidable trauma patients with basic management guidelines as well as some practical tips. In summary, and most importantly, these patients should be treated as any other multitrauma patient. First aid is essential and can be provided by non-medical staff. Initial medical management should focus on the usual, familiar trauma algorithms of ABCDEF from the emergency management of severe burns (EMSB) manual(1) or the ABCDEs of the manual of advanced trauma life support (ATLS)(2) or advanced burn life support (ABLS). Medical care should proceed through the following steps Step one: establish a reliable intravenous infusion; step two: protect the airway; step three: establish and maintain a haemodynamic state compatible with sufficient organ perfusion in order to reduce aggravation of the burn wounds and increase overall survival likelihood; step four: provide analgesia with adequate sedation and provide anaesthesia for escharotomy, fasciotomy or other surgical injuries; step five: maintain normothermia; step six: feed the patient by starting enteral nutrition as early as possible; step seven: prevent infection using antiseptic wound management, systemic antibiotics and tetanus prophylaxis. All of these intricate steps require continuous reassessment and adjustment, but the existence of other wounds (blast injuries, penetrating and blunt trauma) even further complicates the management of bum casualties