B-Cell Precursor Abnormalities in Childhood Acute Lymphoblastic Leukemia

__Abstract__ Despite the improvement in prognosis of childhood acute lymphoblastic leukemia (ALL) due to the implementation of relapse risk stratification, the majoritiy of relapses occurs in cases that were initially not considered as high-risk. Furthermore, current therapies are designed in the fifties and sixties of the past century and result toxicity. Therfore, there is a need for better relapse risk stratification and newly designed drugs that specifcally target leukemic cells. This thesis identifies the interaction and independency of different recently introduced relapse risk markers. It demonstrates that both BCR-ABL1-like gene expression signature and all variants of IKZF1 deletions are correlated to an unfavorable prognosis in B-cell precursor ALL (BCP-ALL). These observations resulted in the implementation of IKZF1 deletions in the currect DCOG ALL-11 treatment protocol. Furthermore, this thesis demonstrates that TCF3-rearranged BCP-ALL is characterized by an activated pre B-cell receptor. This pathway may be used for targetting leukemic cells in future clinical trials

Organizational Probes:Exploring Playful Interactions in Work Environment

Playfulness, with non-intrusive elements, can be considered a useful resource for enhancing social awareness and community building within work organizations. Taking inspirations from the cultural probes approach, we developed organizational probes as a set of investigation tools that could provide useful information about employees’ everyday playful experiences within their work organizations. In an academic work environment, we applied our organizational probes over a period of three weeks. Based on the collected data we developed two design concepts for playful technologies in work environments

Online discussion compensates for suboptimal timing of supportive information presentation in a digitally supported learning environment

This study used a sequential set-up to investigate the consecutive effects of timing of supportive information presentation (information before vs. information during the learning task clusters) in interactive digital learning materials (IDLMs) and type of collaboration (personal discussion vs. online discussion) in computer-supported collaborative learning (CSCL) on student knowledge construction. Students (N = 87) were first randomly assigned to the two information presentation conditions to work individually on a case-based assignment in IDLM. Students who received information during learning task clusters tended to show better results on knowledge construction than those who received information only before each cluster. The students within the two separate information presentation conditions were then randomly assigned to pairs to discuss the outcomes of their assignments under either the personal discussion or online discussion condition in CSCL. When supportive information had been presented before each learning task cluster, online discussion led to better results than personal discussion. When supportive information had been presented during the learning task clusters, however, the online and personal discussion conditions had no differential effect on knowledge construction. Online discussion in CSCL appeared to compensate for suboptimal timing of presentation of supportive information before the learning task clusters in IDLM

Omgewingsvraagstukke en internasionale verhoudinge: 'n historiese perspektief

A significant amount of consensus among large numbers of states in the world presently exists with regard to environmental issues and how these problems must and can be addressed. This consensus includes agreements on the fact that if the international community is not prepared to work together in alleviating these problems the continued existence ofthe world, as we know it, is indeed at risk. What is not well known, however, is how this point of consensus was reached in historical terms. What really happened during the last forty years to achieve international co-operation on environmental issues? This article is an attempt to clarify the complicated history of how international relations were influenced by environmental issues. It also highlights multi-lateral diplomacy as a necessary instrument for advancing the goal of an environmentally safer world

A nationwide survey of patient problem occurrence across different nursing healthcare sectors

Aim: The aim of this study was to determine the patient problems that nurses encounter in different clinical settings and the extent to which they report being able to influence those patient problems. Design: Exploratory online survey research. Method Data were collected through an online questionnaire. We prepared a 2 × 2 matrix to compare the rate of occurrence against the average level of reported influence. Descriptive statistics were used for the data analysis. Results: A total of 440 nurses working in different settings completed the questionnaire. Nurses report having the most influence on patient problems related to self-care, mobility and functions of the skin. Nurses experience less influence on problems with voice/speech and the tasks required for participation in work/employment

The effect of three years of TNF alpha blocking therapy on markers of bone turnover and their predictive value for treatment discontinuation in patients with ankylosing spondylitis: a prospective longitudinal observational cohort study

INTRODUCTION: The aim of this study was to investigate the effect of three years of tumor necrosis factor-alpha (TNF-alpha) blocking therapy on bone turnover as well as to analyze the predictive value of early changes in bone turnover markers (BTM) for treatment discontinuation in patients with ankylosing spondylitis (AS). METHODS: This is a prospective cohort study of 111 consecutive AS outpatients who started TNF-alpha blocking therapy. Clinical assessments and BTM were assessed at baseline, three and six months, as well as at one, two, and three years. Z-scores of BTM were calculated to correct for age and gender. Bone mineral density (BMD) was assessed yearly. RESULTS: After three years, 72 patients (65%) were still using their first TNF-alpha blocking agent. In these patients, TNF-alpha blocking therapy resulted in significantly increased bone-specific alkaline phosphatase, a marker of bone formation; decreased serum collagen-telopeptide (sCTX), a marker of bone resorption; and increased lumbar spine and hip BMD compared to baseline. Baseline to three months decrease in sCTX Z-score (HR: 0.394, 95% CI: 0.263 to 0.591), AS disease activity score (ASDAS; HR: 0.488, 95% CI: 0.317 to 0.752), and physician's global disease activity (HR: 0.739, 95% CI: 0.600 to 0.909) were independent inversely related predictors of time to treatment discontinuation because of inefficacy or intolerance. Early decrease in sCTX Z-score correlated significantly with good long-term response regarding disease activity, physical function and quality of life. CONCLUSIONS: Three years of TNF-alpha blocking therapy results in a bone turnover balance that favors bone formation, especially mineralization, in combination with continuous improvement of lumbar spine BMD. Early change in sCTX can serve as an objective measure in the evaluation of TNF-alpha blocking therapy in AS, in addition to the currently used more subjective measures

Development of Unsteady Aerodynamic and Aeroelastic Reduced-Order Models Using the FUN3D Code

Recent significant improvements to the development of CFD-based unsteady aerodynamic reduced-order models (ROMs) are implemented into the FUN3D unstructured flow solver. These improvements include the simultaneous excitation of the structural modes of the CFD-based unsteady aerodynamic system via a single CFD solution, minimization of the error between the full CFD and the ROM unsteady aero- dynamic solution, and computation of a root locus plot of the aeroelastic ROM. Results are presented for a viscous version of the two-dimensional Benchmark Active Controls Technology (BACT) model and an inviscid version of the AGARD 445.6 aeroelastic wing using the FUN3D code