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Understanding how software works and writing a program are currently frequent requirements when hiring employees. The complexity of learning programming often results in educational failures, student frustration and lack of motivation, because different students prefer different learning paths. Although e-learning courses have led to many improvements in the methodology and the supporting technology for more effective programming learning, misunderstanding of programming principles is one of the main reasons for students leaving school early. Universities face a challenging task: how to harmonise students’ education, focusing on advanced knowledge in the development of software applications, with students’ education in cases where writing code is a new skill. The article proposes a conceptual framework focused on the comprehensive training of future programmers using microlearning and automatic evaluation of source codes to achieve immediate feedback for students. This framework is designed to involve students in the software development of virtual learning environment software that will provide their education, thus ensuring the sustainability of the environment in line with modern development trends. The paper’s final part is devoted to verifying the contribution of the presented elements through quantitative research on the introductory parts of the framework. It turned out that although the application of interactive features did not lead to significant measurable progress during the first semester of study, it significantly improved the results of students in subsequent courses focused on advanced programming.

Purpose: Nijmegen breakage syndrome (NBS) is a DNA repair disorder with a high predisposition to hematologic malignancies. Experimental Design: We describe the natural history of NBS, including cancer incidence, risk of death, and the potential effectiveness of hematopoietic stem cell transplantation (HSCT) in preventing both pathologies: malignancy and immunodeficiency. Results: Among 241 patients with NBS enrolled in the study from 11 countries, 151 (63.0%) patients were diagnosed with cancer. Incidence rates for primary and secondary cancer, tumor characteristics, and risk factors affecting overall survival (OS) were estimated. The cumulative cancer incidence was 40.21% ± 3.5% and 77.78% ± 3.4% at 10 years and 20 years of follow-up, respectively. Most of the tumors n = 95 (62.9%) were non-Hodgkin lymphomas. Overall, 20 (13.2%) secondary malignancies occurred at a median age of 18 (interquartile range, 13.7–21.5) years. The probability of 20-year overall survival (OS) for the whole cohort was 44.6% ± 4.5%. Patients who developed cancer had a shorter 20-year OS than those without malignancy (29.6% vs. 86.2%; P < 10−5). A total of 49 patients with NBS underwent HSCT, including 14 patients transplanted before malignancy. Patients with NBS with diagnosed cancer who received HSCT had higher 20-year OS than those who did not (42.7% vs. 30.3%; P = 0.038, respectively). In the group of patients who underwent preemptive transplantation, only 1 patient developed cancer, which is 6.7 times lower as compared with nontransplanted patients [incidence rate ratio 0.149 (95% confidence interval, 0.138–0.162); P < 0.0001]. Conclusions: There is a beneficial effect of HSCT on the long-term survival of patients with NBS transplanted in their first complete remission of cancer.

Allogeneic HSCT represents the only potentially curative treatment for very high risk (VHR) ALL. Two consecutive international prospective studies, ALL-SCT-(I)BFM 2003 and 2007 were conducted in 1150 pediatric patients. 569 presented with VHR disease leading to any kind of HSCT. All patients >2 year old were transplanted after TBI-based MAC. The median follow-up was 5 years. 463 patients were transplanted from matched donor (MD) and 106 from mismatched donor (MMD). 214 were in CR1. Stem cell source was unmanipulated BM for 330 patients, unmanipulated PBSC for 135, ex vivo T-cell depleted PBSC for 62 and cord-blood for 26. There were more advanced disease, more ex vivo T-cell depletion, and more chemotherapy based conditioning regimen for patients transplanted from MMD as compared to those transplanted from MSD or MD. Median follow up (reversed Kaplan Meier estimator) was 4.99 years, median follow up of survivals was 4.88, range (0.01–11.72) years. The 4-year CI of extensive cGvHD was 13 ± 2% and 17 ± 4% (p = NS) for the patients transplanted from MD and MMD, respectively. 4-year EFS was statistically better for patients transplanted from MD (60 ± 2% vs. 42 ± 5%, p p

Background: Based on previous retrospective results, we investigated the association of coagulation FXIII subunit A (FXIII-A) expression pattern on survival and correlations with known prognostic factors of B-cell progenitor (BCP) childhood acute lymphoblastic leukemia (ALL) as a pilot study of the prospective multi-center BFM ALL-IC 2009 clinical trial. Methods: The study included four national centers (n = 408). Immunophenotyping by flow cytometry and cytogenetic analysis were performed by standard methods. Copy number alteration was studied in a subset of patients (n = 59). Survival rates were estimated by Kaplan-Meier analysis. Correlations between FXIII-A expression patterns and risk factors were investigated with Cox and logistic regression models. Results: Three different patterns of FXIII-A expression were observed: negative (&lt, 20%), dim (20&ndash, 79%), and bright (&ge, 80%). The FXIII-A dim expression group had significantly higher 5-year event-free survival (EFS) (93%) than the FXIII-A negative (70%) and FXIII-A bright (61%) groups. Distribution of intermediate genetic risk categories and the &ldquo, B-other&rdquo, genetic subgroup differed significantly between the FXIII-A positive and negative groups. Multivariate logistic regression confirmed independent association between the FXIII-A negative expression characteristics and the prevalence of intermediate genetic risk group. Conclusions: FXIII-A negativity is associated with dismal survival in children with BCP-ALL and is an indicator for the presence of unfavorable genetic alterations.

Sickle cell disease is one of the most common, life-threatening, non-communicable diseases in the world and a major public health problem. Following the implementation of simple preventive and therapeutic modalities, infant mortality has almost been abolished in high-income countries, but only a small amount of progress has been made in improving survival in adulthood. Progressive end-organ damage, partly related to a systemic vasculopathy, is increasingly recognised. With the availability of a variety of novel disease-modifying drugs, gene addition and gene editing strategies, matched sibling donor haematopoietic stem cell transplantation (HSCT) in children (offering an overall survival rate of 95% and an event-free survival rate of 92%), and encouraging outcomes after alternative donor HSCT, the new challenge is to risk stratify patients, revise transplantation indications, and define the best therapeutic approach for each patient. The ultimate challenge will be to enable these advances in low-income and middle-income countries, where disease prevalence is highest and where innovative strategies are most needed.

Contains fulltext : 229571.pdf (Publisher’s version ) (Closed access) BACKGROUND: An increasing number of NFKB1 variants are being identified in patients with heterogeneous immunologic phenotypes. OBJECTIVE: To characterize the clinical and cellular phenotype as well as the management of patients with heterozygous NFKB1 mutations. METHODS: In a worldwide collaborative effort, we evaluated 231 individuals harboring 105 distinct heterozygous NFKB1 variants. To provide evidence for pathogenicity, each variant was assessed in silico; in addition, 32 variants were assessed by functional in vitro testing of nuclear factor of kappa light polypeptide gene enhancer in B cells (NF-κB) signaling. RESULTS: We classified 56 of the 105 distinct NFKB1 variants in 157 individuals from 68 unrelated families as pathogenic. Incomplete clinical penetrance (70%) and age-dependent severity of NFKB1-related phenotypes were observed. The phenotype included hypogammaglobulinemia (88.9%), reduced switched memory B cells (60.3%), and respiratory (83%) and gastrointestinal (28.6%) infections, thus characterizing the disorder as primary immunodeficiency. However, the high frequency of autoimmunity (57.4%), lymphoproliferation (52.4%), noninfectious enteropathy (23.1%), opportunistic infections (15.7%), autoinflammation (29.6%), and malignancy (16.8%) identified NF-κB1-related disease as an inborn error of immunity with immune dysregulation, rather than a mere primary immunodeficiency. Current treatment includes immunoglobulin replacement and immunosuppressive agents. CONCLUSIONS: We present a comprehensive clinical overview of the NF-κB1-related phenotype, which includes immunodeficiency, autoimmunity, autoinflammation, and cancer. Because of its multisystem involvement, clinicians from each and every medical discipline need to be made aware of this autosomal-dominant disease. Hematopoietic stem cell transplantation and NF-κB1 pathway-targeted therapeutic strategies should be considered in the future.

Market discipline has been a scrutinized area since the last financial crisis in 2008. Regulators strengthened their role particularly through Pillar 3 in Basel III. However, there are still some aspects of market discipline that deserve special attention to avoid future failures. This study focuses on the analysis of the interest and behaviour of deposit stakeholders based on website data dedicated to disclosures of commercial bank in Slovakia during and after turbulent times (period 2009-2012). The data consists of log files, and web mining techniques were applied (the modelling of web user behaviour in dependence on time - based on the proposals of the authors). The results show that also in turbulent times, stakeholders’ interest in Pillar 3 disclosures is low (in line with ( Munk, Pilkova, Benko, & Blažekova, 2017 )) and the highest interest was identified for the Pricing List category. After turbulent times, Pillar 3 categories (Pillar 3 related information and Pillar 3 disclosures) have weak interest, with peaks at the beginning of the year, and the highest increase was in the Business Conditions category. The results suggest that the enhancement of interest of key stakeholders in disclosures inevitably requires changes to deliver sufficient disclosure data structures and to design a disclosure policy that fulfils regulatory expectations.

Learning Analytics is a rapidly growing area of interest in the higher educational institutions worldwide. Its effective utilization depends on the proper selection of strategy of the learning analytics architecture implementation. The paper compares several learning analytics architectures and describes their main building components. Consequently, the proposal and current state of the learning analytics architecture implementation at the university environment is discussed. The conclusion provides several recommendations, open questions and tasks, which rose during the implementation process and require the future research.

Despite attempts to improve the definitions of ambiguous lineage leukemia (ALAL) during the last 2 decades, general therapy recommendations are missing. Herein, we report a large cohort of children with ALAL and propose a treatment strategy. A retrospective multinational study (International Berlin-Frankfurt-Munster Study of Leukemias of Ambiguous Lineage [iBFM-AMBI2012]) of 233 cases of pediatric ALAL patients is presented. Survival statistics were used to compare the prognosis of subsets and types of treatment. Five-year event-free survival (EFS) of patients with acute lymphoblastic leukemia (ALL)-type primary therapy (80% ± 4%) was superior to that of children who received acute myeloid leukemia (AML)-type or combined-type treatment (36% ± 7.2% and 50% ± 12%, respectively). When ALL- or AML-specific gene fusions were excluded, 5-year EFS of CD19+ leukemia was 83% ± 5.3% on ALL-type primary treatment compared with 0% ± 0% and 28% ± 14% on AML-type and combined-type primary treatment, respectively. Superiority of ALL-type treatment was documented in single-population mixed phenotype ALAL (using World Health Organization and/or European Group for Immunophenotyping of Leukemia definitions) and bilineal ALAL. Treatment with ALL-type protocols is recommended for the majority of pediatric patients with ALAL, including cases with CD19+ ALAL. AML-type treatment is preferred in a minority of ALAL cases with CD19- and no other lymphoid features. No overall benefit of transplantation was documented, and it could be introduced in some patients with a poor response to treatment. As no clear indicator was found for a change in treatment type, this is to be considered only in cases with ≥5% blasts after remission induction. The results provide a basis for a prospective trial.

Magnusiomyces capitatus (previously known as Geotrichum capitatum or Blastoschizomyces capitatus or Trichosporon capitatum) is a rare cause of fungal infection in immunocompromised patients. Most of these cases (87%) have been reported from the Mediterranean region, as it is extremely rare to recognize it in other regions. Here we report a first case of disseminated M. capitatus infection in Slovakia. The patient – 19 year old woman with myelodysplastic syndrome was diagnosed with M. capitatus fungemia after allogeneic stem cell transplantation. The infection occurred despite antifungal prophylaxis with micafungin, which was in vitro sensitive to the yeast. The treatment according to minimal inhibitory concentrations (micafungin, voriconazol) and granulocyte transfusions were administered. M. capitatus was cleared out from the bloodstream. However, patient died of multiple organ failure. Autopsy showed multiple lesions in organs, but did not prove presence of yeast by histopathology. M. capitatus was confirmed by polymerase chain reaction from all tested organs: heart, brain, lungs, spleen, liver and kidneys. We present the post mortem pictures showing the yeast lesions in affected organs. 2012 Elsevier Ltd. All rights reserved.

The chapter aims at finding out how students from selected universities in different European countries use e-environment and e-resources at their universities. Students’ opinion was gathered using a survey. The questionnaire consisted of 14 questions and created the basis for the evaluation of a university e-environment. It was assumed that participants of e-environment (academic teachers, students, administration) are involved in activities with the six different benefits. Almost 900 responses from five different countries joined in the project IRNet under European Union Seventh Framework program (Poland, Czech Republic, Slovakia, Ukraine and Russian Federation) were collected. The chapter presents the analysis of the answers with the result that students require a broad Internet connection and electronic versions of study material, but do not want to publish own achievements in a university e-environment. Half of the students require printed publications and students do not widely use scientific resources when searching for learning materials.

The paper focuses on modelling of commercial bank website visitors’ behaviour. The authors analyse domestic and foreign market participants’ interests in mandatory financial information disclosure of a commercial bank during the recent financial crisis and try to answer the question whether the purposes of Basel 2 regulations under the Pillar 3 – Market discipline, publishing financial information, have been fulfilled. The authors analyse bank website logs files using web log mining methods to better understand the rate of using of web pages, where mandatory financial information about Basel 2 is published. After data pre-processing the authors use association rule analysis to identify the association among content categories of the website. The results show that there is small interest in mandatory financial information disclosure by the commercial bank in general. The foreign website visitors take more concern in mandatory financial information disclosure, and they take less interest in general information about bank than domestic ones.

We use data cleaning, integration, reduction and data conversion methods in the pre-processing level of data analysis. Data processing techniques improve the overall quality of the patterns mined. The paper describes using of standard pre-processing methods for preparing data of the commercial bank website in the form of the log file obtained from the web server. Data cleaning, as the simplest step of data pre-processing, is non-trivial as the analysed content is highly specific. We had to deal with the problem of frequent changes of the content and even frequent changes of the structure. Regular changes in the structure make use of the sitemap impossible. We presented approaches how to deal with this problem. We were able to create the sitemap dynamically just based on the content of the log file. In this case study, we also examined just the one part of the website over the standard analysis of an entire website, as we did not have access to all log files for the security reason. As the result, the traditional practices had to be adapted for this special case. Analysing just the small fraction of the website resulted in the short session time of regular visitors. We were not able to use recommended methods to determine the optimal value of session time. Therefore, we proposed new methods based on outliers identification for raising the accuracy of the session length in this paper.

This article presents examples of good practice in the creation of an information and educational environment and comprehensive, systematic and effective use of the Internet services offered by The Faculty of Ethnology and Sciences of Education in Cieszyn (University of Silesia), Faculty of Science, Constantine the Philosopher University in Nitra and Pedagogical faculty of University of Ostrava: its official web-site, distance learning platform, project sites, conference sites as well as the distance learning platform, based on the LMS Moodle system is intended several important didactic and scientific aims and tasks. The article also describes some results of research, conducted within the framework of IRNet Project (www.irnet.us.edu.pl) and Work Package 3 “Analyses and evaluation of the ICT level, e-learning and intercultural developments in every participating countries” at the University of Silesia and at the Faculty of Ethnology and Sciences of Education, Constantine the Philosopher University in Nitra, Pedagogical faculty of University of Ostrava: project of educational institution. DOI: https://doi.org/10.28925/2414-0325.2015.1.20741

The objective of the paper is the verification of the fulfilment of the purposes of Basel II, Pillar 3 - market discipline during the recent financial crisis. The objective of the paper is to describe the current state of the working out of the project that is focused on the analysis of the market participants' interest in mandatory disclosure of financial information by a commercial bank by means of advanced methods of web log mining. The output of the realized project will be the verification of the assumptions related to the purposes of Basel III by means of the web mining methods, the recommendations for possible reduction of mandatory disclosure of information under Basel II and III, the proposal of the methodology for data preparation for web log mining in this application domain and the generalised procedure for users' behaviour modelling dependent on time. The schedule of the project has been divided into three phases. The paper deals with its first phase that is focusing on the data pre-processing, analysis and evaluation of the required information under Basel II, Pillar 3 since 2008 and its disclosure into the web site of a commercial bank. The authors introduce the methodologies for data preparation and known heuristic methods for path completion into web log files with respect to the particularity of investigated application domain. They propose scientific methods for modelling users' behaviour of the webpages related to Pillar 3 with respect to time.

Introduction: Subunit A of blood coagulation factor XIII (FXIIIA) may be expressed in leukemic B-cell precursor (BCP) lymphoblasts in addition to platelets, megakaryocytes, monocytes and macrophages (Kiss F. et al Thromb Haemost 2006;96:172-82.). In a retrospective single-center cohort of children with acute lymphoblastic leukemia (ALL) treated with the BFM ALL-IC 2002 protocol, expression of FXIIIA was correlated with statistically significant survival advantage (Kárai B et al. Pathol Oncol Res 2018; 24:345-52.). Our aim was to investigate the impact of FXIIIA expression pattern on EFS and its correlation with known clinical and genetic prognostic factors in a multi-center pilot study within the frames of the BFM ALL-IC 2009 clinical trial (EuDract: 2010-019722-13). Patients and Methods: We examined 317 children with BCP-ALL between 2011 and 2018 at institutions in Poland (n=188), Hungary (n=116), and Slovakia (n=13). Patients with Down-syndrome, t(9;22), and infants ( Results: We observed 3 different patterns of FXIIIA expression in leukemic lymphoblasts: negative pattern (80%). Evaluation of FC histograms of the moderate positive pattern showed that FXIIIA expression increased continuously which excluded the existence of distinct FXIIIA negative and FXIIIA positive subpopulations within the moderate positive expression group (Fig.1). In contrast to the previous single-center retrospective cohort, EFS of patients with FXIIIA positive BCP-ALL was not significantly different from that of patients of FXIIIA negative BCP-ALL (Fig.2A). However, a significant EFS advantage of patients with moderate FXIIIA positivity was demonstrated when compared with patients with FXIIIA negative BCP-ALL (p=0.019), and with patients with FXIIIA strong positive BCP-ALL (p=0.001) (Fig.2B). The 3 different FXIIIA expression patterns did not correlate significantly with either risk stratification according to BFM ALL-IC 2009 or FC MRD categories. Intermediate genetic risk categories (low hyperdiploidy, t(1;19), and "B-other") were significantly more prevalent (p=0.042) among patients with FXIIIA negative BCP-ALL than among patients with strong FXIIIA positive BCP-ALL. The "B-other" subgroup was also significantly more prevalent (p=0.022) among patients of the above 2 groups (Table 1). Distribution of the "B-other" genetic group and the prednisone response differed significantly between the FXIIIA positive and negative groups. Intermediate genetic risk group is mostly made up of patients assigned to the "B-other" group explaining the significant difference between the FXIIIA positive and negative groups, in terms that FXIIIA negative patients had 50% lower chance of facing low instead of intermediate genetic risk compared to FXIIIA positive patients. The multivariate logistic regression analysis confirmed the association between the FXIIIA characteristics and the intermediate genetic risk group. This association persisted after adjusting for categorical variables, i.e. gender, age, WBC, and BFM ALL-IC 2009 stratification (Table 2). High risk copy number alterations were detected in 4/7 samples of the FXIIIA negative group and in 1/17 of the FXIIIA positive group. Conclusions: FXIIIA expression status of leukemic lymphoblasts can easily be determined by FC. Patients with FXIIIA negative lymphoblasts should be further investigated with sophisticated and more expensive genetic and molecular methods. Grant sponsor: OTKA K108885. Disclosures No relevant conflicts of interest to declare.

Presumptions of each data analysis are data themselves, regardless of the analysis focus (visit rate analysis, optimization of portal, personalization of portal, etc.). Results of selected analysis highly depend on the quality of analyzed data. In case of portal usage analysis, these data can be obtained by monitoring web server log file. We are able to create data matrices and web map based on these data which will serve for searching for behaviour patterns of users. Data preparation from the log file represents the most time-consuming phase of whole analysis. We realized an experiment so that we can find out to which criteria are necessary to realize this time-consuming data preparation. We aimed at specifying the inevitable steps that are required for obtaining valid data from the log file. Specially, we focused on the reconstruction of activities of the web visitor. This advanced technique of data preprocessing belongs to time consuming one. In the article we tried to assess the impact of reconstruction of activities of a web visitor on the quantity and quality of the extracted rules which represent the web users’ behaviour patterns.

The 620Trp variant of the LYP protein, encoded by the lymphoid tyrosine phosphatase 22 gene (PTPN22), is associated with autoimmunity. In this study we aimed at characterising the role of this variant on lymphocyte activation. We analysed cytokine secretion and proliferation of peripheral blood mononuclear cells (PBMCs) and CD4(+)T cells in a cohort of clinically non-diabetic, multiple autoantibody-positive children, healthy controls and in children with type 1 diabetes (T1D). We found a decreased proliferation and IL-2 production of CD4(+)T cells after anti-CD3/anti-CD28 stimulation (p=0.04 for IL-2) among T1D patients. In addition, a profoundly decreased intracellular calcium flux in CD4(+)T cells after PHA stimulus was detected among 620Trp carriers. In contrast, no effect of this polymorphism on tuberculin and tetanus toxoid induced PBMC proliferation and cytokine secretion was observed in autoantibody positive children, healthy controls and children with newly-diagnosed T1D. In conclusion, the LYP 620Trp variant is associated with reduced activation, proliferation and IL-2 production in CD4(+)T cells among T1D patients. In accordance with our previous findings on the key role of this variant on disease progression, this mechanism is likely to contribute to the development of beta-cell specific autoimmunity.

The aim of our study was to determine, how severe calorie restriction in anorexia nervosa (AN) may influence regulatory T (Treg) cells and their cellular networks, that is, their main inducers (dendritic cells (DC) and monocytes) and their target cells, CD4+ lymphocytes.We measured the prevalence of Tregs, myeloid and plasmocytoid DC. The prevalence of tumor necrosis factor-alpha (TNF-alpha) and interleukin (IL)-12-positive monocytes, IL-2, IL-4 and interferon (IFN)-gamma positive CD4+ cells was determined by intracellular staining after activation.In total, 21 AN patients and 19 healthy age-matched controls (body mass index values, median (range): 14.9 (11.1-17.4) vs 23.2 (19.5-27.4) kg/m(2)) have been recruited.Prevalence of Tregs, DCs, TNF-alpha and IL-12-positive monocytes, IL-4 and IFN-gamma-producing CD4+ cells were similar in AN and controls. The prevalence of IL-2-positive CD4+ cells was somewhat lower in AN (% value, median (range): 12.05 (7.50-16.70) vs 14.40 (12.00-22.00), P0.05). None of these parameters correlated with the patients' clinical characteristics.Our results suggest that the antigen presenting cell - regulatory T cell - CD4+ lymphocyte axis is not affected by calorie and nutritional deficiency.

The paper analyses usefulness of the Pillar 3 financial and risk information disclosures to the commercial banks users. The Pillar 3 are specific regulatory disclosures requirements set out in the Basel 2 framework and incorporated into EU law and subsequently laws of the member states. According to Pillar 3 intention market participants should be able to understand and subsequently judge the relevance of the bank risk position and risk management and try to discipline “risky” banks. Due to that the European authorities are focused on control and improvements of the banks’ disclosures. However, less is done as far as usefulness of the Pillar 3 risk information to the commercial banks users is. The authors try to assess at which extent is information useful for users of the banks that operate in countries where banking sectors are dominated by foreign-owned entities and depositors (sophisticated and non sophisticated; insured and uninsured; primarily non-financial ones) is a key source of market discipline. The authors focus on modelling of visitor behaviours at website where financial and risk information according to Pillar 3 requirements is available. The results show that there is in general small interest in Pillar 3 information and even financial and risk related information belongs to those where interests is the lowest one.

Clinical and genetic heterogeneity renders confirmation or exclusion of autoimmune lymphoproliferative syndrome difficult. To re-evaluate and improve the currently suggested diagnostic approach to patients with suspected FAS mutation, the most frequent cause of autoimmune lymphoproliferative syndrome, we prospectively determined 11 biomarkers in 163 patients with splenomegaly or lymphadenopathy and presumed or proven autoimmune cytopenia(s). Among 98 patients sequenced for FAS mutations in CD3(+)TCRα/β(+)CD4(-)CD8(-) "double negative" T cells, 32 had germline and six had somatic FAS mutations. The best a priori predictor of FAS mutations was the combination of vitamin B12 and soluble FAS ligand (cut-offs 1255 pg/mL and 559 pg/mL, respectively), which had a positive predictive value of 92% and a negative predictive value of 97%. We used these data to develop a web-based probability calculator for FAS mutations using the three most discriminatory biomarkers (vitamin B12, soluble FAS ligand, interleukin-10) of the 11 tested. Since more than 60% of patients with lymphoproliferation and autoimmune cytopenia(s) in our cohort did not harbor FAS mutations, 15% had somatic FAS mutations, and the predictive value of double-negative T-cell values was rather low (positive and negative predictive values of 61% and 77%, respectively), we argue that the previously suggested diagnostic algorithm based on determination of double-negative T cells and germline FAS sequencing, followed by biomarker analysis, is not efficient. We propose vitamin B12 and soluble FAS ligand assessment as the initial diagnostic step with subsequent decision on FAS sequencing supported by a probability-calculating tool. peerReviewed

The European Standards and Guidelines for Quality Assurance (ESG) present nowadays the most famous and frequently used documents in the field of quality assurance in higher education. The authors deal with the problem of ESG implementation at the university. They propose a model of support information system, which covers all parts defined in ESG. This model divides the problem of internal guidelines for quality assurance implementation into modules and schematically depicts their mutual relations. The authors discuss each module in detail and give reasons for their inclusion in the proposed model.

Acute leukemia (AL) of ambiguous lineage (AMBI-L) comprises up to 5% of AL cases in both children and adults. Although several definitions exist, a general treatment guideline has been missing. Single country studies usually report fewer than 50 cases of children or adults. Accordingly, the international iBFM AMBI2012 Study/Registry collected 275 AMBI-L cases in patients In total, 275 patients were included in the study. Of these, 240 fulfilled the definitions of biphenotypic/mixed phenotype AL, partially overlapping with cases in whom two clones had been identified (n=68) and 15 cases presented with undifferentiated AL. Most patients started their treatment with an ALL-type protocol (n=161), 79 with AML therapy, 27 with a combined regimen, including the Interfant protocols, 2 patients were not treated, 2 received other treatment, and in 4 patients such information was missing. The 5yEFS of the entire cohort was 56±3.7% and 5y overall survival was 67±3.3%. Patients treated by ALL-type protocols had superior 5 year event free survival (5yEFS) (70±4.6%, n=158) compared to those who started AML-type treatment (5yEFS: 40±6.4%, n=78) or hybrid ALL/AML treatment (5yEFS: 50±11%, n=27). Although protocol selection was likely biased, we recommend ALL treatment, when diagnostic findings, including molecular genetics, fail to indicate AML therapy. Although myeloperoxidase (MPO) has been used as the ultimate marker of myeloid lineage, patients who started with ALL-type treatment demonstrated a better prognosis even among cases classified as MPOpos/part pos (Fig. 1). These differences by initial choice of treatment are most prominent when CD19pos/part pos cases are analyzed regardless of the overall lineage (Fig. 2). This shows that at least for CD19pos/part pos cases in the absence of RUNX1/RUNX1T1 fusion, treatment should not start with current AML-type protocols. Until week 12, patients with higher leukemia burden were slightly overrepresented compared to non-AMBI ALL patients (data not shown). In addition, patients with higher residual disease had a much poorer prognosis. Thus, Prednisone poor and good responders (based on day 8 blood blast counts) had a 5yEFS of 50±9.7%, n=38 and 81±5.8%, n=82, respectively (p=0.005). By day 15 bone marrow (BM), only cutoffs of 10-4 and 10-3 were analyzed and neither showed significant associations with EFS. At the end of induction, patients with BM residual disease ≥10-3 had a 5yEFS of 51±10%, n=49 compared to 90±4.3% for those with lower levels, n=75 (p=0.0002). Especially higher residual disease at week 12 was associated with an extremely poor EFS (Fig. 3). Early identification of patients with inadequate response and designing alternative treatment for them is our important challenge. No overall benefit of transplantation was seen in patients who started on ALL treatment or hybrid ALL/AML treatment. Again, this may be caused by a biased selection of more severe cases for transplant. In patients who started with AML treatment, transplant appeared to improve prognosis (Fig. 4). This study provides the basis for improved treatment of future patients with AMBI-L, with more accurate diagnostics. OH, AL, IJ, EM and JS were supported by Czech Health Research Council 15-28525A. Disclosures Bleckmann: JazzPharma: Other: financial support of travel costs. Moricke:JazzPharma: Honoraria, Other: financial support of travel costs. Inaba:Arog: Research Funding. Kattamis:Novartis: Honoraria, Research Funding; ApoPharma: Honoraria. Reinhardt:Boehringer Ingelheim: Membership on an entity's Board of Directors or advisory committees; Celgene: Research Funding; Jazz Pharma: Other: Travel Accomodation; Celgene: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees.

The paper introduces the proof of concept of the e-learning courses quality evaluation framework and its implementation into the quality assurance in higher education. We summarize general issues of the internal quality assurance. We pay more attention to the evaluation of the e-learning course quality framework itself in the context of Part 1 of European Standards and Guidelines for internal quality assurance within educational institution. Finally, we try to generalize found observations and create set of procedural rules.

Simulation modeling of computer networks is an effective technique for evaluating the performance of network and data transfer with various internet protocols. In this paper we are focusing on the impact of used transport layer protocol transferred with new internet protocol (IPv6) against network performance, especially network router load and efficiency. Higher values of load or worse efficiency can be a problem in global IPv6 deployment. We propose methodology of traffic measurement based on different stochastic systems. We are able to generate different TCP, UDP and SCTP traffic according to uniform probability distribution for packet inter departure time and packet size. We use a generator that is able to reproduce experiment by using the same seed for random values and we focus on the correlation of packet size, inter departure time to router and communicating nodes load. All experiments were made in pure IPv4 environment and in native IPv6 environment too. We expected that the use of a new protocol lead to higher efficiency of data transfer. By using forward stepwise regression analysis we identify which variables imply the packet transfer time.

Systemic inflammation is characteristic for preeclampsia (PE). A hypothesis for immune dysregulation is that the function of regulatory T cells (CD4(+)FoxP3(+), Tregs) inhibiting the activation of lymphocytes is impaired. We investigated the proportion of Tregs and their cellular network in preeclamptic women. Fifteen preeclamptic and 17 healthy pregnant women were enrolled in the 32nd gestational week (median age 29 (range 22-45) and 32 (range 26-38) years, respectively). PE was diagnosed according to international criteria at a median of 30 gestational weeks (range 21-31). Peripheral blood was taken and blood mononuclear cells were isolated. Flow cytometry was used to determine the proportion of regulatory (CD4+FoxP3+) T cells, lymphoid and myeloid dendritic cells, natural killer and natural killer T cells, naive and memory and activated CD4+ and CD8+cells. The proportion of Tregs and that of naive CD4(+)CD45RA(+) cells was lower in preeclamptic than in control women (p=0.025, p=0.04, respectively). The proportion of other investigated cell types did not differ. Low Treg numbers may support the notion that PE shares similar features to autoimmune disorders. Low Treg numbers are not reflected in the proportion of activated lymphocytes, at least in this stage of pregnancy. This does not exclude, however, the functional alterations of these cell types.

Up to 5% of patients with acute leukemia (AL) are diagnosed as AL of ambiguous lineage. The ambiguous lineage ALs consist of mixed phenotype AL (MPAL, or biphenotypic AL, BAL), bilineal AL, switching AL and rare, undifferentiated ALs. From a molecular genetic point of view, they overlap with several molecular genetic subsets such as AL with MLL rearrangements or early T precursor AL. As no general treatment strategy exists, these patients have been variably treated with lymphoblastic (ALL)- , myeloid (AML)- or combined (hybrid) therapy, with or without stem cell transplant. They are often unreported as they are excluded from standard protocols. So far, attempts to shed more light on these patients has largely focused on definitions of ambiguous lineage AL. Only limited therapeutic observations have been possible in studies on this AL subset, usually reporting 50 or fewer pediatric/adult patients. In order to facilitate more detailed analyses, we have created an international study "iBFM AMBI2012 Study/Registry". In this study, patients under 18 years at diagnosis are eligible. Each center/country was asked to report all consecutive patients with ambiguous lineage AL, from a 2- to 13-year period ending May 31, 2015. The definitions included those with WHO and EGIL criteria and remained unchanged throughout the study. Complete information on type of treatment, follow up and immunophenotype was requested. Where available (n=101 at the time of this abstract uploading), raw cytometric FCS data files were stored centrally for review. Apart from the study itself, the central database served also as a basis for consulting individual patients during the diagnostic workup. Furthermore, data on fusion genes, cytogenetics, treatment response and availability of specimens for collateral studies were also collected. In total, 247 patients from Australia, Austria, Brazil, Czechia, Germany, Greece, Israel, Netherlands, NOPHO (Denmark, Estonia, Finland, Norway, Sweden, Iceland and Lithuania), PINDA (Chile), Poland, SAHOP (Argentina), Slovakia, St. Jude Children's Research Hospital (USA), Ukraine and United Kingdom are reported. Among those, 222 fulfilled the definitions of MPAL/BAL, partially overlapping with cases in whom two clones had been identified (n=47) and 14 cases presented with undifferentiated AL. Most of them, consistent with our general treatment guideline (Figure 1), started their treatment with an ALL type of protocol (n=150), 60 patients started on AML therapy, 8 patients received a combined regimen including the Interfant protocols, 2 patients were not treated, 13 received other treatment, and this information is missing in 9 patients (additional 5 pts. started on ALL treatment but their follow up information is incomplete). The 5 year event free survival of the entire cohort was 55±4% and its separation by first type of treatment is shown in Figure 2. In a collateral study, we set up a qPCR array on 90 genes that are characteristic of the lymphoid or myeloid lineages and/or are thought to be involved in their regulation. Using this array, sorted cells of granulocytic, monocytic, T, and B lineages at various stages of development (17 stages total) were analyzed and compared to samples of AL including 6 samples of MPAL of precursor B/myeloid phenotype. Although this array did not show a general deregulation in the MPAL genome compared to that in AL or healthy cells, subtle changes were seen such as decrease of CEBPE and LILRA2 gene expression, in comparison to classical B precursor ALL. Overall, our data shows that the general treatment guideline (Figure 1), which favors ALL treatment is justified by the outcome. However, although this study is larger than those published, caution is needed during its interpretation due to variations in diagnostics and treatment among the participating countries. Therefore, our data should be viewed as a basis for non-ambiguous treatment guidelines that will direct each patient to either ALL or AML treatment. These guidelines will be tested prospectively. In addition, the framework of this study is being used as a basis of consulting new AL cases with diagnostic uncertainties. Furthermore, it serves as a data resource for biologic studies. Supported by AZV 15-28525A, UNCE 204012, NT/14534-3, NT/13462-4, P302/12/G101. Disclosures Kattamis: Novartis: Research Funding, Speakers Bureau; ApoPharma: Speakers Bureau.

Abstract 2539 Introduction: Transient leukemia (TL) occurs in 5 to 10% of newborns with Down syndrome (DS). In almost all cases it resolves spontaneously within 3 months, but 20–25% of the children develop myeloid leukemia (ML-DS) until the age of 4 years. TL and ML-DS can occur also in children without any clinical signs of Down syndrome, but with constitutional trisomy 21 due to mosaicism. It can be difficult to diagnose TL or ML-DS in these children and the treatment strategies have not been defined. Patients/Material: Between 1/2002 and 7/2011, 15 newborns and infants were diagnosed with DS mosaic. Nine of them presented with TL and 8 children suffered from ML-DS; 2 of them with a history of TL (table 1). In children without any stigmata the special morphology and immunophenotype of blasts triggered the screening for GATA1 mutation and trisomy 21 mosaic. Diagnostic work-up was performed according to standard guidelines: morphology, immunophenotyping (IP), cytogenetics and FISH (trisomy 21), molecular genetics (GATA 1 mutation screening). Screening of GATA1 mutations was done with direct sequencing of PCR product (Exon1, Exon2, and Exon3). For monitoring of GATA1 mutant clone qPCR have been used with patient specific TaqMan probes and primers. Mosaic was detected by cytogenetics or FISH in bone marrow, blood and/or fibroblasts. Results: All newborns with TL achieved complete remission (CR). Due to clinical symptoms caused by the leukemic blasts, in 3 children low-dose cytarabine was applied. One patient died due to cardiovascular failure. In all patients GATA 1 mutation was confirmed. Minimal residual disease by qPCR (mutation-specific probes) or immunophenotyping (IP) revealed negativity in 3 out of 3 children monitored (follow-up 2 to 10.1 yrs). Two children with (unknown) trisomy 21 mosaic were diagnosed as acute megakaryoblastic leukemia (AMKL) and treated according the high risk arm of the AML-BFM 2004 including allogeneic stem cell transplantation (one child), GATA1 mutation was identified retrospectively. Both children are alive in CR. Six children with ML-DS were initially treated according the AML-BFM protocol. After ML-DS was confirmed, therapy was continued with the intensity reduced schedule according to the ML-DS 2006 protocol. All children are still in CR (follow-up 1.5 to 6.7 years, median 2.4 yrs). This was confirmed by MRD-monitoring, which achieved negativity after two treatment elements (qPCR Conclusions: GATA1 mutated leukemia has to be excluded in all young children with AMKL ( Disclosures: No relevant conflicts of interest to declare.