Sample records for aml mds und

  1. Myeloablative radioimmunotherapies in the conditioning of patients with AML, MDS and multiple myeloma prior to stem cell transplantation; Myeloablative Radioimmuntherapien zur Konditionierung bei Patienten mit AML, MDS und multiplem Myelom vor Stammzelltransplantation

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    Buchmann, I. [Abt. fuer Nuklearmedizin, Universitaetsklinik Heidelberg (Germany)


    Aggressive consolidation chemotherapy and hematopoietic stem cell transplantation have improved the prognosis of patients with acute myeloid leukemia (AML), myelodyplastic syndrome (MDS) and multiple myeloma. Nevertheless, only a minor fraction of patients achieve long-term disease-free survival after stem cell transplantation with disease recurrence being the most common cause of treatment failure. In addition, therapy-related effects such as toxicity of chemotherapy and complications of stem cell transplantation increase mortality rates significantly. Myeloablative radioimmunotherapy uses radiolabeled monoclonal antibodies (mAb) with affinity for the hematopoietic marrow. It applies high radiation doses in the bone marrow but spares normal organs. Adding myeloablative radioimmunotherapy to the conditioning schemes of AML, MDS and multiple myeloma before stem cell transplantation allows for the achievement of a pronounced antileukemic/antimyeloma effect for the reduction of relapse rates without significant increase of acute organ toxicity and therapy-related mortality. In order to optimise therapy, a rational design of the nuclide-antibody combination is necessary. {sup 90}Y, {sup 188}Re and {sup 131}I are the most frequently used {beta}{sup -}-particles. Of these, {sup 90}Y is the most qualified nuclide for myeloablation. Backbone stabilised DTPA are ideal chelators to stably conjugate {sup 90}Y to antibodies so far. For myeloablative conditioning, anti-CD66-, -45- and -33-mAb are used. The anti-CD66-antibody BW250/183 binds to normal hematopoietic cells but not to leukemic blasts and myeloma cells. The {sup 90}Y-2B3M-DTPA-BW250/183 is the most suited radioimmunoconjugate for patients with an infiltration grade of leukemic blasts in the bone marrow < 25%. The specific doses (Gy/GBq) are 10.2 {+-} 1.8 (bone marrow), 2.7 {+-} 2 (liver) and < 1 (kidneys). In contrast, radiolabeled anti-CD33- and anti-CD45-antibodies bind to both, most of white blood cells and

  2. PD-1 signaling and inhibition in AML and MDS. (United States)

    Haroun, Faysal; Solola, Sade A; Nassereddine, Samah; Tabbara, Imad


    Acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) are clinically and molecularly heterogeneous clonal myeloid disorders with a poor prognosis especially in the relapsed refractory setting and in patients above the age of 60. While allogeneic hematopoietic stem cell transplantation (ASCT) is a potentially curative approach, high relapse, morbidity, and mortality rates necessitate the development of alternative therapies. Immune checkpoint inhibitors unmask tumoral immune tolerance and have demonstrated efficacy in the treatment of chemotherapy-resistant hematologic and solid malignancies. The rationale for the investigation of those agents in AML and MDS is supported by an observed increased expression of programmed cell death 1 protein (PD-1) and ligand 1 (PD-L1) in the hematopoietic microenvironment of AML and MDS, and its association with low TP53 and a poor prognosis. Early clinical experience in combination with a hypomethylating agent has shown encouraging responses; however, larger clinical trials are needed to determine the role of checkpoint inhibition in myeloid malignancies.

  3. IL8-CXCR2 pathway inhibition as a therapeutic strategy against MDS and AML stem cells. (United States)

    Schinke, Carolina; Giricz, Orsolya; Li, Weijuan; Shastri, Aditi; Gordon, Shanisha; Barreyro, Laura; Barreryo, Laura; Bhagat, Tushar; Bhattacharyya, Sanchari; Ramachandra, Nandini; Bartenstein, Matthias; Pellagatti, Andrea; Boultwood, Jacqueline; Wickrema, Amittha; Yu, Yiting; Will, Britta; Wei, Sheng; Steidl, Ulrich; Verma, Amit


    Acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) are associated with disease-initiating stem cells that are not eliminated by conventional therapies. Novel therapeutic targets against preleukemic stem cells need to be identified for potentially curative strategies. We conducted parallel transcriptional analysis of highly fractionated stem and progenitor populations in MDS, AML, and control samples and found interleukin 8 (IL8) to be consistently overexpressed in patient samples. The receptor for IL8, CXCR2, was also significantly increased in MDS CD34(+) cells from a large clinical cohort and was predictive of increased transfusion dependence. High CXCR2 expression was also an adverse prognostic factor in The Cancer Genome Atlas AML cohort, further pointing to the critical role of the IL8-CXCR2 axis in AML/MDS. Functionally, CXCR2 inhibition by knockdown and pharmacologic approaches led to a significant reduction in proliferation in several leukemic cell lines and primary MDS/AML samples via induction of G0/G1 cell cycle arrest. Importantly, inhibition of CXCR2 selectively inhibited immature hematopoietic stem cells from MDS/AML samples without an effect on healthy controls. CXCR2 knockdown also impaired leukemic growth in vivo. Together, these studies demonstrate that the IL8 receptor CXCR2 is an adverse prognostic factor in MDS/AML and is a potential therapeutic target against immature leukemic stem cell-enriched cell fractions in MDS and AML. © 2015 by The American Society of Hematology.

  4. Age-related epigenetic drift in the pathogenesis of MDS and AML. (United States)

    Maegawa, Shinji; Gough, Sheryl M; Watanabe-Okochi, Naoko; Lu, Yue; Zhang, Nianxiang; Castoro, Ryan J; Estecio, Marcos R H; Jelinek, Jaroslav; Liang, Shoudan; Kitamura, Toshio; Aplan, Peter D; Issa, Jean-Pierre J


    The myelodysplastic syndrome (MDS) is a clonal hematologic disorder that frequently evolves to acute myeloid leukemia (AML). Its pathogenesis remains unclear, but mutations in epigenetic modifiers are common and the disease often responds to DNA methylation inhibitors. We analyzed DNA methylation in the bone marrow and spleen in two mouse models of MDS/AML, the NUP98-HOXD13 (NHD13) mouse and the RUNX1 mutant mouse model. Methylation array analysis showed an average of 512/3445 (14.9%) genes hypermethylated in NHD13 MDS, and 331 (9.6%) genes hypermethylated in RUNX1 MDS. Thirty-two percent of genes in common between the two models (2/3 NHD13 mice and 2/3 RUNX1 mice) were also hypermethylated in at least two of 19 human MDS samples. Detailed analysis of 41 genes in mice showed progressive drift in DNA methylation from young to old normal bone marrow and spleen; to MDS, where we detected accelerated age-related methylation; and finally to AML, which markedly extends DNA methylation abnormalities. Most of these genes showed similar patterns in human MDS and AML. Repeat element hypomethylation was rare in MDS but marked the transition to AML in some cases. Our data show consistency in patterns of aberrant DNA methylation in human and mouse MDS and suggest that epigenetically, MDS displays an accelerated aging phenotype.

  5. [Application of Next Generation Sequencing for AML/MDS Diagnosis and Treatment]. (United States)

    Cheng, Huan-Chen; Liu, Sheng-Wei; Liu, Yu; Zhao, Xue-Fei; Li, Wei; Qiu, Lin; Ma, Jun


    To detect the mutations of AML/MDS- related genes by using next generation sequencing (NGS), to analyze the mutation levels of each genes in the AML/MDS and the sensitivity of NGS, and to evaluate the feasibility of gene mutations for monitoring the MRD and predicating the progression of diseases. The specimens were collected from primary AML (68 cases) and MDS (57 cases) patients from August 2015 to June 2016 in the Harbin Institute of Hematology and Oncology. The mutations of 22 related genes were detected by using AML/MDS-NGS chips. TET2 gene showed the highest mutation rate in AML (55.9%) and MDS (56.1%). The gene mutations were as follows: CEBPA (11.8%), DNMT3A (7.4%), C-KIT (7.4%) and FLT3-ITD (7.4%) in AML, and U2AF1 (10.5%) and SRSF2 (10.5%) in MDS. All the genes had specific mutation sites except TP53 and CEBPA. The mutations of FLT3, C-KIT and CEBPA became negative in the 5 AML patients in remission when compared with those at primary attack, but the mutation rate of TET2 gene was not obviously changed, whereas the mutation rate of the 5 MDS patients was not significantly changed. The new gene mutations appeared in 3 MDS patients with disease progression, but the mutation rate was not changed significantly in the disease progression. The gene mutation rate still has not been changed significantly even after remission. Both AML and MDS have their own specific mutated genes and sites. Some gene mutations, such as CEBPA, can be used as an effective indicator to monitoring MRD in AML patients, but those only used for the evaluation of the disease progression and prognosis in MDS patients.

  6. Therapy-related AML/MDS after treatment of low-grade B-cell lymphoma

    International Nuclear Information System (INIS)

    Yanada, Masamitsu


    Described is the therapy-related AML (acute myelogenetic leukemia)/MDS (myelo-dysplasia syndrome), which is manifested after various treatments of low-grade B-cell lymphoma and has strongly attracted attention because of the markedly improved prognosis due to recent advantages of the therapy for the disease. AML/MDS occurs several years after chemotherapy and/or radiation therapy which cause DNA damage in hematopoietic cells, and the AML/MDS risk is known increased in patients undergone especially with autologous transplantation of those cells. AML/MDS has the feature similar to that caused either by alkylating agent or by topoisomerase-2 inhibitor, and the disease by radiation belong to the former. Yet unclear is the problem whether malignant cells causing the disease after therapy are derived from the remaining cells in the graft or in the body. Although irradiations of total body and total lymphaden as well as chemotherapy are said to be related to AML/MDS and local irradiation does not contribute to its risk, the most important factor for the disease is considered to be the autotransplantation as the recurrence occurs in 50% after it. Thus the treatment history should be taken into consideration for suppressing AML/MDS, for which follow up with consideration for the disease is required particularly after autotransplantation. (R.T.)

  7. The emerging role of immune checkpoint based approaches in AML and MDS. (United States)

    Boddu, Prajwal; Kantarjian, Hagop; Garcia-Manero, Guillermo; Allison, James; Sharma, Padmanee; Daver, Naval


    The development of immune checkpoint inhibitors represents a major breakthrough in the field of cancer therapeutics. Pursuant to their success in melanoma and numerous solid tumor malignancies, these agents are being investigated in hematological malignancies including acute myelogenous leukemia (AML) and myelodysplastic syndromes (MDS). Although AML/MDS have traditionally been considered to be less immunogenic than solid tumor malignancies, recent pre-clinical models suggest a therapeutic role for immune checkpoint inhibition in these diseases. CTLA-4 inhibition may be especially effective in treating late post-allogeneic stem cell transplant relapse of AML in patients with limited or no graft versus host disease. Immune checkpoint inhibition, specifically PD-1 inhibition, demonstrated limited single agent efficacy in patients with relapsed AML and with MDS post-hypomethylating therapy. Rationally designed combinations of PD-1 inhibitors with standard anti-leukemic therapy are needed. Hypomethylating agents such as azacitidine, up-regulate PD-1, PD-L1, and PD-L2 in patients with AML/MDS and up-regulation of these genes was associated with the emergence of resistance. The combination of azacitidine and PD-1/PD-L1 inhibition may be a potential mechanism to prevent or overcome resistance to 5-azacitidine. A number of such combinations are being evaluated in clinical trials with early encouraging results. Immune checkpoint inhibition is also an attractive option to improve relapse-free survival or eliminate minimal residual disease post induction and consolidation by enhancing T-cell surveillance in patients with high-risk AML. The ongoing clinical trials with checkpoint inhibitors in AML/MDS will improve our understanding of the immunobiology of these diseases and guide us to the most appropriate application of these agents in the therapy of AML/MDS.

  8. Focal Adhesion Kinase as a Potential Target in AML and MDS. (United States)

    Carter, Bing Z; Mak, Po Yee; Wang, Xiangmeng; Yang, Hui; Garcia-Manero, Guillermo; Mak, Duncan H; Mu, Hong; Ruvolo, Vivian R; Qiu, Yihua; Coombes, Kevin; Zhang, Nianxiang; Ragon, Brittany; Weaver, David T; Pachter, Jonathan A; Kornblau, Steven; Andreeff, Michael


    Although overexpression/activation of focal adhesion kinase (FAK) is widely known in solid tumors to control cell growth, survival, invasion, metastasis, gene expression, and stem cell self-renewal, its expression and function in myeloid leukemia are not well investigated. Using reverse-phase protein arrays in large cohorts of newly diagnosed acute myeloid leukemia (AML) and myeloid dysplastic syndrome (MDS) samples, we found that high FAK expression was associated with unfavorable cytogenetics ( P = 2 × 10 -4 ) and relapse ( P = 0.02) in AML. FAK expression was significantly lower in patients with FLT3 -ITD ( P = 0.0024) or RAS ( P = 0.05) mutations and strongly correlated with p-SRC and integrinβ3 levels. FAK protein levels were significantly higher in CD34 + ( P = 5.42 × 10 -20 ) and CD34 + CD38 - MDS ( P = 7.62 × 10 -9 ) cells compared with normal CD34 + cells. MDS patients with higher FAK in CD34 + cells tended to have better overall survival ( P = 0.05). FAK expression was significantly higher in MDS patients who later transformed to compared with those who did not transform to AML and in AML patients who transformed from MDS compared with those with de novo AML. Coculture with mesenchymal stromal cells (MSC) increased FAK expression in AML cells. Inhibition of FAK decreased MSC-mediated adhesion/migration and viability of AML cells and prolonged survival in an AML xenograft murine model. Our results suggest that FAK regulates leukemia-stromal interactions and supports leukemia cell survival; hence, FAK is a potential therapeutic target in myeloid leukemia. Mol Cancer Ther; 16(6); 1133-44. ©2017 AACR . ©2017 American Association for Cancer Research.

  9. Gene expression profiling in MDS and AML: potential and future avenues

    DEFF Research Database (Denmark)

    Theilgaard-Mönch, K; Boultwood, J; Ferrari, S


    Today, the classification systems for myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) already incorporate cytogenetic and molecular genetic aberrations in an attempt to better reflect disease biology. However, in many MDS/AML patients no genetic aberrations have been identified yet...... with regard to diagnosis, prediction of clinical outcome, discovery of novel subclasses and identification of novel therapeutic targets and novel drugs. As many challenges remain ahead, we discuss the pitfalls of this technology and its potential including future integrative studies with other genomics...

  10. Connect MDS/AML: design of the myelodysplastic syndromes and acute myeloid leukemia disease registry, a prospective observational cohort study. (United States)

    Steensma, David P; Abedi, Medrdad; Bejar, Rafael; Cogle, Christopher R; Foucar, Kathryn; Garcia-Manero, Guillermo; George, Tracy I; Grinblatt, David; Komrokji, Rami; Ma, Xiaomei; Maciejewski, Jaroslaw; Pollyea, Daniel A; Savona, Michael R; Scott, Bart; Sekeres, Mikkael A; Thompson, Michael A; Swern, Arlene S; Nifenecker, Melissa; Sugrue, Mary M; Erba, Harry


    Myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) are myeloid neoplasms in which outgrowth of neoplastic clones disrupts normal hematopoiesis. Some patients with unexplained persistent cytopenias may not meet minimal diagnostic criteria for MDS but an alternate diagnosis is not apparent; the term idiopathic cytopenia of undetermined significance (ICUS) has been used to describe this state. MDS and AML occur primarily in older patients who are often treated outside the clinical trial setting. Consequently, our understanding of the patterns of diagnostic evaluation, management, and outcomes of these patients is limited. Furthermore, there are few natural history studies of ICUS. To better understand how patients who have MDS, ICUS, or AML are managed in the routine clinical setting, the Connect MDS/AML Disease Registry, a multicenter, prospective, observational cohort study of patients newly diagnosed with these conditions has been initiated. The Connect MDS/AML Disease Registry will capture diagnosis, risk assessment, treatment, and outcomes data for approximately 1500 newly diagnosed patients from approximately 150 community and academic sites in the United States in 4 cohorts: (1) lower-risk MDS (International Prognostic Scoring System [IPSS] low and intermediate-1 risk), with and without del(5q); (2) higher-risk MDS (IPSS intermediate-2 and high risk); (3) ICUS; and (4) AML in patients aged ≥ 55 years (excluding acute promyelocytic leukemia). Diagnosis will be confirmed by central review. Baseline patient characteristics, diagnostic patterns, treatment patterns, clinical outcomes, health economics outcomes, and patient-reported health-related quality of life will be entered into an electronic data capture system at enrollment and quarterly for 8 years. A tissue substudy to explore the relationship between karyotypes, molecular markers, and clinical outcomes will be conducted, and is optional for patients. The Connect MDS/AML Disease

  11. [Combination of busulfan with increased-dose of fludarabine as conditioning regimen for MDS and MDS-AML patients with allo-HSCT]. (United States)

    Yuan, Jing; Ren, Hanyun; Qiu, Zhixiang; Li, Yuan; Wang, Mangju; Liu, Wei; Xu, Weilin; Sun, Yuhua; Wang, Lihong; Liang, Zeyin; Dong, Yujun; Ou, Jinping; Wang, Wensheng; Yin, Yue; Cen, Xinan; Wang, Qian


    To investigate the safety and efficacy of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for myelodysplastic syndrome (MDS) and secondary acute myelogenous leukemia (MDS-AML) using conditioning regimen with busulfan (Bu) and increased-dose of fludarabine (ID-Flu). A total of 49 patients with MDS or MDS-AML were treated by allo-HSCT, the clinical data was analyzed retrospectively. All patients achieved hematopoietic reconstitution. Neutrophil engraftment was at 10 - 22 days (median 13 days), and platelet engraftment was at 8 - 66 days (median 16 days). The cumulative incidences of Ⅱ-Ⅳ degree acute graft-versus-host disease (GVHD), hemorrhagic cystitis (HC), and hepatic venous occlusive disease (VOD) were 28.6%, 14.3% and 2.0%, respectively. The transplant-related mortality (TRM) was only 4.1% at 100d and 8.2% at 1-92 months of followed-up (median 14 months) period. Overall survival (OS) and disease free survival (DFS) was 75.5%, 73.5%, respectively. Kaplan-Meier curve showed that 3-year OS and 3-year DFS was (71.1 ± 7.8)%, (66.7 ± 8.3)%, respectively, with a relapse incidence (RI) 16.3%. OS for MDS and MDS-AML was 81.5% and 68.2%, and RI in two settings was 3.7%, 31.8%, respectively. OS for MDS-AML at complete remission (CR) and non-CR subgroup was 83.3% and 50.0%, respectively, while cumulative RR was 16.7% and 50.0%, respectively. OS and RI except for non-CR subgroup were 82.1% and 7.7%. Univariate analysis showed that pre-HSCT disease status had correlation with OS (P=0.031), but age, decitabine in conditioning regimen, stem cell source, HLA matching, patient-donor gender, dose of mononuclear cells and GVHD had no correlation with OS. Bu/ID-Flu conditioning regimen for MDS and MDS-AML has high efficiency, fewer complications, lower toxicity and TRM. The OS and DFS were higher and RI was lower except for refractory MDS-AML patients. The regimen is valuable for clinical application.

  12. Therapy Related AML/MDS Following Treatment for Childhood Cancer: Experience from a Tertiary Care Centre in North India. (United States)

    Vyas, Chintan; Jain, Sandeep; Kapoor, Gauri


    Therapy-related acute myeloid leukemia/myelodysplastic syndrome (t-AML/MDS) is a devastating late effect of cancer treatment. There is limited data on incidence of t-AML/MDS from India. We retrospectively studied pediatric t AML/MDS at our institute between January 1996 and December 2015. Among 1285 children, 8 patients developed t-AML with a median age of 15.5 years. Overall incidence of t-AML/MDS was 0.62% [0.99% (4/402) in solid tumours and 0.45% (4/883) in leukemia/lymphoma, P  = 0.26] with 6390 patient years of follow up. Primary malignancy included sarcoma [bone (2), soft tissue (2)], B-non-Hodgkin lymphoma (2) and acute lymphoblastic leukemia (2). The median cumulative equivalent doses of cyclophosphamide, doxorubicin and etoposide were 6.8, 270 and 2.5 gm/m 2 respectively. Two patients received radiotherapy [rhabdomyosarcoma (50 Gy), synovial sarcoma (45 Gy)]. The median latency period to develop t-AML/MDS was 24 months (range 16.5-62 months). Most common FAB morphology was M4/M5 (7/8) and cytogenetic abnormality was MLL rearrangement (4/8). Five patients opted for treatment, 4 achieved remission out of which 2 patients are alive and disease free. Short latency periods, absence of pre-leukemic phase and 11q23 translocations were characteristic in the patients with t-AML/MDS. In view of poor outcome with conventional therapy, novel strategies and prevention need to be considered.

  13. Defining AML and MDS second cancer risk dynamics after diagnoses of first cancers treated or not with radiation

    NARCIS (Netherlands)

    Radivoyevitch, T.; Sachs, R. K.; Gale, R. P.; Molenaar, R. J.; Brenner, D. J.; Hill, B. T.; Kalaycio, M. E.; Carraway, H. E.; Mukherjee, S.; Sekeres, M. A.; Maciejewski, J. P.


    Risks of acute myeloid leukemia (AML) and/or myelodysplastic syndromes (MDS) are known to increase after cancer treatments. Their rise-and-fall dynamics and their associations with radiation have, however, not been fully characterized. To improve risk definition we developed SEERaBomb R software for

  14. Paclitaxel Induced MDS and AML: A Case Report and Literature Review

    Directory of Open Access Journals (Sweden)

    Udit Bhaskar Bhatnagar


    Full Text Available Therapy related acute myelogenous leukemia (AML and myelodysplastic syndromes (MDS have been classically linked to alkylating agents and topoisomerase inhibitors. They constitute about 1% of all AMLs. There is less evidence on association of taxanes (paclitaxel and docetaxel with these myeloid neoplasms. We present a case of paclitaxel therapy related acute myelogenous leukemia after treatment of endometrial cancer with a regimen containing paclitaxel and carboplatin. A 63-year-old female underwent surgery followed by a total of 6 cycles of chemotherapy with carboplatin and paclitaxel. Six months after last cycle of chemotherapy, she was diagnosed with myelodysplastic syndrome with refractory anemia and excess blasts. Six weeks later, she had worsening anemia and thrombocytopenia which prompted a bone marrow biopsy which revealed acute myelomonocytic leukemia. A thorough literature review revealed 12 other case reports where taxanes have been implicated in the development of therapy related myeloid neoplasm. Based on the timeline of events in our patient, paclitaxel is the likely culprit in the pathogenesis of this myeloid neoplasm. This rare but significantly grave adverse effect should be kept in consideration when deciding on treatment options for gynecological malignancies.

  15. A review of therapy-related myelodysplastic syndromes and acute myeloid leukaemia (t-MDS/AML) in Irish patients: a single centre experience. (United States)

    Maung, Su W; Burke, Cathie; Hayde, Jennifer; Walshe, Janice; McDermott, Ray; Desmond, Ronan; McHugh, Johnny; Enright, Helen


    To demonstrate the incidence, characteristics, treatment and outcomes of patients with therapy-related myelodysplastic syndromes and therapy-related acute myeloid leukaemia (t-MDS/AML) in a tertiary referral centre. Patients meeting the diagnostic criteria for t-MDS/AML from 2003 to 2014 were reviewed to analyse their diagnostic features, details of antecedent disorder and treatment, approach to management and survival. 39 patients who developed t-MDS/AML were identified with incidence of 8.7%. Median age and gender distribution were similar to de novo MDS but t-MDS/AML patients had greater degree of cytopenia and adverse karyotypes. Time to development of t-MDS/AML was shortest for patients with antecedent haematological malignancy compared to solid tumours and autoimmune disorders (46, 85 and 109 months). Patients with prior acute leukaemia had the shortest latency and poor overall survival. Treatment options included best supportive care (56%), Azacitidine (31%) or intensive chemotherapy/allogeneic transplant (13%). Median OS of all patients was 14 months. Survival declined markedly after two years and 5-year OS was 13.8%. Longer survival was associated with blast count MDS/AML patients showed unique characteristics which influenced their treatment and outcomes. IPSS-R may be useful in risk-adapted treatment approaches and can predict outcomes. Survival remains poor but improved outcomes were seen with allogeneic transplantation. Azacitidine may be effective in patients unfit for intensive therapies.

  16. Downregulation but lack of promoter hypermethylation or somatic mutations of the potential tumor suppressor CXXC5 in MDS and AML with deletion 5q

    DEFF Research Database (Denmark)

    Treppendahl, Marianne Bach; Möllgård, L; Hellström-Lindberg, E


    During recent years mutations in epigenetic modulators have been identified in several human cancers, including acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS)[1]. CXXC5 has been found to be necessary for retinoic acid induced differentiation of myelocytic leukemia cells, identify......During recent years mutations in epigenetic modulators have been identified in several human cancers, including acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS)[1]. CXXC5 has been found to be necessary for retinoic acid induced differentiation of myelocytic leukemia cells...

  17. Myeloablative radioimmunotherapies in the conditioning of patients with AML, MDS and multiple myeloma prior to stem cell transplantation

    International Nuclear Information System (INIS)

    Buchmann, I.


    Aggressive consolidation chemotherapy and hematopoietic stem cell transplantation have improved the prognosis of patients with acute myeloid leukemia (AML), myelodyplastic syndrome (MDS) and multiple myeloma. Nevertheless, only a minor fraction of patients achieve long-term disease-free survival after stem cell transplantation with disease recurrence being the most common cause of treatment failure. In addition, therapy-related effects such as toxicity of chemotherapy and complications of stem cell transplantation increase mortality rates significantly. Myeloablative radioimmunotherapy uses radiolabeled monoclonal antibodies (mAb) with affinity for the hematopoietic marrow. It applies high radiation doses in the bone marrow but spares normal organs. Adding myeloablative radioimmunotherapy to the conditioning schemes of AML, MDS and multiple myeloma before stem cell transplantation allows for the achievement of a pronounced antileukemic/antimyeloma effect for the reduction of relapse rates without significant increase of acute organ toxicity and therapy-related mortality. In order to optimise therapy, a rational design of the nuclide-antibody combination is necessary. 90 Y, 188 Re and 131 I are the most frequently used β - -particles. Of these, 90 Y is the most qualified nuclide for myeloablation. Backbone stabilised DTPA are ideal chelators to stably conjugate 90 Y to antibodies so far. For myeloablative conditioning, anti-CD66-, -45- and -33-mAb are used. The anti-CD66-antibody BW250/183 binds to normal hematopoietic cells but not to leukemic blasts and myeloma cells. The 90 Y-2B3M-DTPA-BW250/183 is the most suited radioimmunoconjugate for patients with an infiltration grade of leukemic blasts in the bone marrow 90 Y-anti-CD45-mAb YAML568 are 6.4 ± 1.2 (bone marrow), 3.9 ± 1.4 (liver) and 1.1 ± 0.4 (kidneys). CD45 is expressed also on the extramedullar clonogenic myeloma progenitor cell that circulates in the peripheral blood. Thus, the conditioning of

  18. Dendritic cells (DCs) can be successfully generated from leukemic blasts in individual patients with AML or MDS: an evaluation of different methods. (United States)

    Kremser, Andreas; Dressig, Julia; Grabrucker, Christine; Liepert, Anja; Kroell, Tanja; Scholl, Nina; Schmid, Christoph; Tischer, Johanna; Kufner, Stefanie; Salih, Helmut; Kolb, Hans Jochem; Schmetzer, Helga


    Myeloid-leukemic cells (AML, MDS, CML) can be differentiated to leukemia-derived dendritic cell [DC (DCleu)] potentially presenting the whole leukemic antigen repertoire without knowledge of distinct leukemia antigens and are regarded as promising candidates for a vaccination strategy. We studied the capability of 6 serum-free DC culture methods, chosen according to different mechanisms, to induce DC differentiation in 137 cases of AML and 52 cases of MDS. DC-stimulating substances were cytokines ("standard-medium", "MCM-Mimic", "cytokine-method"), bacterial lysates ("Picibanil"), double-stranded RNA ["Poly (I:C)"] or a cytokine bypass method ("Ca-ionophore"). The quality/quantity of DC generated was estimated by flow cytometry studying (co) expressions of "DC"antigens, costimulatory, maturation, and blast-antigens. Comparing these methods on average 15% to 32% DC, depending on methods used, could be obtained from blast-containing mononuclear cells (MNC) in AML/MDS cases with a DC viability of more than 60%. In all, 39% to 64% of these DC were mature; 31% to 52% of leukemic blasts could be converted to DCleu and DCleu-proportions in the suspension were 2% to 70% (13%). Average results of all culture methods tested were comparable, however not every given case of AML could be differentiated to DC with 1 selected method. However performing a pre-analysis with 3 DC-generating methods (MCM-Mimic, Picibanil, Ca-ionophore) we could generate DC in any given case. Functional analyses provided proof, that DC primed T cells to antileukemia-directed cytotoxic cells, although an anti-leukemic reaction was not achieved in every case. In summary our data show that a successful, quantitative DC/DCleu generation is possible with the best of 3 previously tested methods in any given case. Reasons for different functional behaviors of DC-primed T cells must be evaluated to design a practicable DC-based vaccination strategy.

  19. Pathophysiology of MDS: genomic aberrations. (United States)

    Ichikawa, Motoshi


    Myelodysplastic syndromes (MDS) are characterized by clonal proliferation of hematopoietic stem/progenitor cells and their apoptosis, and show a propensity to progress to acute myelogenous leukemia (AML). Although MDS are recognized as neoplastic diseases caused by genomic aberrations of hematopoietic cells, the details of the genetic abnormalities underlying disease development have not as yet been fully elucidated due to difficulties in analyzing chromosomal abnormalities. Recent advances in comprehensive analyses of disease genomes including whole-genome sequencing technologies have revealed the genomic abnormalities in MDS. Surprisingly, gene mutations were found in approximately 80-90% of cases with MDS, and the novel mutations discovered with these technologies included previously unknown, MDS-specific, mutations such as those of the genes in the RNA-splicing machinery. It is anticipated that these recent studies will shed new light on the pathophysiology of MDS due to genomic aberrations.

  20. Myelodysplastic changes mimicking MDS following treatment for osteosarcoma

    DEFF Research Database (Denmark)

    Løhmann, Ditte

    -MDS/AML) is a feared long-term complication of paediatric cancer including osteosarcoma. Few develop t-MDS/AML, but it is not known how many have significant haematological changes after finishing treatment for osteosarcoma. In this study we reviewed biochemistry from a consecutive series of children for up to two...... years after finishing treatment. We included all children (n=14) who where diagnosed from October 2006 to January 2011 at our department and treated according to the EURAMOS-1 protocol. Four patients relapsed and died before the end of the study period. We found noteworthy changes in MCV, platelets...... for osteosarcoma developed haematological abnormalities similar to early MDS but few developed t-MDS/AML. Close monitoring of patients recovering from osteosarcoma is essential. Keywords: Osteosarcoma, t-MDS/AML, Haematological abnormalities, Children...

  1. GEP analysis validates high risk MDS and acute myeloid leukemia post MDS mice models and highlights novel dysregulated pathways. (United States)

    Guerenne, Laura; Beurlet, Stéphanie; Said, Mohamed; Gorombei, Petra; Le Pogam, Carole; Guidez, Fabien; de la Grange, Pierre; Omidvar, Nader; Vanneaux, Valérie; Mills, Ken; Mufti, Ghulam J; Sarda-Mantel, Laure; Noguera, Maria Elena; Pla, Marika; Fenaux, Pierre; Padua, Rose Ann; Chomienne, Christine; Krief, Patricia


    In spite of the recent discovery of genetic mutations in most myelodysplasic (MDS) patients, the pathophysiology of these disorders still remains poorly understood, and only few in vivo models are available to help unravel the disease. We performed global specific gene expression profiling and functional pathway analysis in purified Sca1+ cells of two MDS transgenic mouse models that mimic human high-risk MDS (HR-MDS) and acute myeloid leukemia (AML) post MDS, with NRASD12 and BCL2 transgenes under the control of different promoters MRP8NRASD12/tethBCL-2 or MRP8[NRASD12/hBCL-2], respectively. Analysis of dysregulated genes that were unique to the diseased HR-MDS and AML post MDS mice and not their founder mice pointed first to pathways that had previously been reported in MDS patients, including DNA replication/damage/repair, cell cycle, apoptosis, immune responses, and canonical Wnt pathways, further validating these models at the gene expression level. Interestingly, pathways not previously reported in MDS were discovered. These included dysregulated genes of noncanonical Wnt pathways and energy and lipid metabolisms. These dysregulated genes were not only confirmed in a different independent set of BM and spleen Sca1+ cells from the MDS mice but also in MDS CD34+ BM patient samples. These two MDS models may thus provide useful preclinical models to target pathways previously identified in MDS patients and to unravel novel pathways highlighted by this study.

  2. GEP analysis validates high risk MDS and acute myeloid leukemia post MDS mice models and highlights novel dysregulated pathways

    Directory of Open Access Journals (Sweden)

    Laura Guerenne


    Full Text Available Abstract Background In spite of the recent discovery of genetic mutations in most myelodysplasic (MDS patients, the pathophysiology of these disorders still remains poorly understood, and only few in vivo models are available to help unravel the disease. Methods We performed global specific gene expression profiling and functional pathway analysis in purified Sca1+ cells of two MDS transgenic mouse models that mimic human high-risk MDS (HR-MDS and acute myeloid leukemia (AML post MDS, with NRASD12 and BCL2 transgenes under the control of different promoters MRP8NRASD12/tethBCL-2 or MRP8[NRASD12/hBCL-2], respectively. Results Analysis of dysregulated genes that were unique to the diseased HR-MDS and AML post MDS mice and not their founder mice pointed first to pathways that had previously been reported in MDS patients, including DNA replication/damage/repair, cell cycle, apoptosis, immune responses, and canonical Wnt pathways, further validating these models at the gene expression level. Interestingly, pathways not previously reported in MDS were discovered. These included dysregulated genes of noncanonical Wnt pathways and energy and lipid metabolisms. These dysregulated genes were not only confirmed in a different independent set of BM and spleen Sca1+ cells from the MDS mice but also in MDS CD34+ BM patient samples. Conclusions These two MDS models may thus provide useful preclinical models to target pathways previously identified in MDS patients and to unravel novel pathways highlighted by this study.

  3. Implication of microRNAs in the Pathogenesis of MDS (United States)

    Fang, Jing; Varney, Melinda; Starczynowski, Daniel T.


    MicroRNAs (miRNAs) are significant regulators of human hematopoietic stem cells (HSC), and their deregulation contributes to hematological malignancies. Myelodysplastic syndromes (MDS) represent a spectrum of hematological disorders characterized by dysfunctional HSC, ineffective blood cell production, progressive marrow failure, and an increased risk of developing acute myeloid leukemia (AML). Although miRNAs have been primarily studied in AML, only recently have similar studies been performed on MDS. In this review, we describe the normal function and expression of miRNAs in human HSC, and describe mounting evidence that deregulation of miRNAs contributes to the pathogenesis of MDS. PMID:22571695

  4. Genetic predisposition syndromes: when should they be considered in the work-up of MDS? (United States)

    Babushok, Daria V; Bessler, Monica


    Myelodysplastic syndromes (MDS) are clonal hematopoietic disorders characterized by cytopenias, ineffective hematopoiesis, myelodysplasia, and an increased risk of acute myeloid leukemia (AML). While sporadic MDS is primarily a disease of the elderly, MDS in children and young and middle-aged adults is frequently associated with underlying genetic predisposition syndromes. In addition to the classic hereditary bone marrow failure syndromes (BMFS) such as Fanconi Anemia and Dyskeratosis Congenita, in recent years there has been an increased awareness of non-syndromic familial MDS/AML predisposition syndromes such as those caused by mutations in GATA2, RUNX1, CEBPA, and SRP72 genes. Here, we will discuss the importance of recognizing an underlying genetic predisposition syndrome a patient with MDS, will review clinical scenarios when genetic predisposition should be considered, and will provide a practical overview of the common BMFS and familial MDS/AML syndromes which may be encountered in adult patients with MDS. Copyright © 2014 Elsevier Ltd. All rights reserved.

  5. Cytogenetic findings in adult secondary acute myeloid leukemia (AML): frequency of favorable and adverse chromosomal aberrations do not differ from adult de novo AML

    DEFF Research Database (Denmark)

    Preiss, Birgitte S; Bergman, Olav J; Friis, Lone S


    During a 15-year period, 161 adult patients were diagnosed with secondary acute myeloid leukemia (s-AML) in the region of Southern Denmark. In 73 patients, the AML diagnosis was preceded by myelodysplastic syndrome (MDS-AML), in 31 patients by an antecedent hematologic disease, and in 57 patients...

  6. High Frequency of AML1/RUNX1 Point Mutations in Radiation-Associated Myelodysplastic Syndrome Around Semipalatinsk Nuclear Test Site


    Dinara, ZHARLYGANOVA; Hironori, HARADA; Yuka, HARADA; Sergey, SHINKAREV; Zhaxybay, ZHUMADILOV; Aigul, ZHUNUSOVA; Naylya J., TCHAIZHUNUSOVA; Kazbek N., APSALIKOV; Vadim, KEMAIKIN; Kassym, ZHUMADILOV; Noriyuki, KAWANO; Akiro, KIMURA; Masaharu, HOSHI; Department of Radiation Biophysics, Research Institute for Radiation Biology and Medicine, Hiroshima University; Department of Hematology and Oncology, Research Institute for Radiation Biology and Medicine, Hiroshima University


    It is known that bone marrow is a sensitive organ to ionizing radiation, and many patients with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) have been diagnosed in radiation-treated cases and atomic bomb survivors in Hiroshima and Nagasaki. The AML1/RUNX1 gene has been known to be frequently mutated in MDS/AML patients among atomic bomb survivors and radiation therapy-related MDS/AML patients. In this study, we investigated the AML1 mutations in radiation-exposed patients wi...

  7. Proposed minimal diagnostic criteria for myelodysplastic syndromes (MDS) and potential pre-MDS conditions. (United States)

    Valent, Peter; Orazi, Attilio; Steensma, David P; Ebert, Benjamin L; Haase, Detlef; Malcovati, Luca; van de Loosdrecht, Arjan A; Haferlach, Torsten; Westers, Theresia M; Wells, Denise A; Giagounidis, Aristoteles; Loken, Michael; Orfao, Alberto; Lübbert, Michael; Ganser, Arnold; Hofmann, Wolf-Karsten; Ogata, Kiyoyuki; Schanz, Julie; Béné, Marie C; Hoermann, Gregor; Sperr, Wolfgang R; Sotlar, Karl; Bettelheim, Peter; Stauder, Reinhard; Pfeilstöcker, Michael; Horny, Hans-Peter; Germing, Ulrich; Greenberg, Peter; Bennett, John M


    Myelodysplastic syndromes (MDS) comprise a heterogeneous group of myeloid neoplasms characterized by peripheral cytopenia, dysplasia, and a variable clinical course with about 30% risk to transform to secondary acute myeloid leukemia (AML). In the past 15 years, diagnostic evaluations, prognostication, and treatment of MDS have improved substantially. However, with the discovery of molecular markers and advent of novel targeted therapies, new challenges have emerged in the complex field of MDS. For example, MDS-related molecular lesions may be detectable in healthy individuals and increase in prevalence with age. Other patients exhibit persistent cytopenia of unknown etiology without dysplasia. Although these conditions are potential pre-phases of MDS they may also transform into other bone marrow neoplasms. Recently identified molecular, cytogenetic, and flow-based parameters may add in the delineation and prognostication of these conditions. However, no generally accepted integrated classification and no related criteria are as yet available. In an attempt to address this challenge, an international consensus group discussed these issues in a working conference in July 2016. The outcomes of this conference are summarized in the present article which includes criteria and a proposal for the classification of pre-MDS conditions as well as updated minimal diagnostic criteria of MDS. Moreover, we propose diagnostic standards to delineate between ´normal´, pre-MDS, and MDS. These standards and criteria should facilitate diagnostic and prognostic evaluations in clinical studies as well as in clinical practice.

  8. Comparison of childhood myelodysplastic syndrome, AML FAB M6 or M7, CCG 2891: report from the Children's Oncology Group. (United States)

    Barnard, Dorothy R; Alonzo, Todd A; Gerbing, Robert B; Lange, Beverly; Woods, William G


    Myelodysplastic syndromes (MDS), acute erythroleukemia (FAB M6), and acute megakaryocytic leukemia (FAB M7) have overlapping features. Children without Down syndrome or acute promyelocytic leukemia who were newly diagnosed with primary myelodysplastic syndrome or acute myeloid leukemia (AML) M6 or M7 were compared to children with de novo AML M0-M5. All children were entered on the Children's Cancer Group therapeutic research study CCG 2891. The presentation and outcomes of the 132 children diagnosed with MDS (60 children), AML FAB M6 (19 children), or AML FAB M7 (53 children) were similar. Children with AML FAB M7 were diagnosed at a significantly younger age (P = 0.001). Children with MDS, M6, or M7 had significantly lower white blood cell (WBC) counts (P = 0.001), lower peripheral blast counts (P M6 and AML M7 resemble MDS in presentation, poor induction success rates, and outcomes.

  9. Atmospheric Measurements Laboratory (AML) (United States)

    Federal Laboratory Consortium — The Atmospheric Measurements Laboratory (AML) is one of the nation's leading research facilities for understanding aerosols, clouds, and their interactions. The AML...

  10. New proposals of the WHO working group (2016) for the diagnosis of myelodysplastic syndromes (MDS): Characteristics of refined MDS types. (United States)

    Strupp, Corinna; Nachtkamp, Kathrin; Hildebrandt, Barbara; Giagounidis, Aristoteles; Haas, Rainer; Gattermann, Norbert; Bennett, John M; Aul, Carlo; Germing, Ulrich


    Based on centrally diagnosed 3528 patients in the Düsseldorf registry, we validated the new proposals for the classification of the MDS by the WHO working group: 256 patients were diagnosed as MDSSLD (7,3%), 978 MDSMLD (27,7%), 227 MDS RS SLD (6,4%); 321 MDS RS MLD (9,1%), 159 MDS del(5q) (4,5%), 481 MDSEB 1 (13,6%), 620 MDSEB 2 (17,6%), and 148 MDS-U (4,2%). 352 patients (16,9% of the non blastic types) changed the category, mainly moving from RCMD to MDS RS MLD, RCUD and RCMD to MDS del(5q). Median survival times of the refined groups differed from more than 60 months in the MDSSLD (RS) groups, 37 months in the MDSMLD (RS) groups, 79 months of the MDS del(5q) group and 21 and 11 months in the MDSEB 1 and 2 groups, respectively. The difference between the groups with regard to the risk of AML evolution was also impressing. No major changes were made with regard to the MDS-U categories. In summary, the proposals of the WHO group for the classification of MDS are thoughtful, taking into account biologic parameters of the diseases, a more precise wording, to some extend pragmatic and feasible. Copyright © 2017 Elsevier Ltd. All rights reserved.

  11. Inhibition of WNT signaling in the bone marrow niche prevents the development of MDS in the Apcdel/+ MDS mouse model. (United States)

    Stoddart, Angela; Wang, Jianghong; Hu, Chunmei; Fernald, Anthony A; Davis, Elizabeth M; Cheng, Jason X; Le Beau, Michelle M


    There is accumulating evidence that functional alteration(s) of the bone marrow (BM) microenvironment contribute to the development of some myeloid disorders, such as myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). In addition to a cell-intrinsic role of WNT activation in leukemia stem cells, WNT activation in the BM niche is also thought to contribute to the pathogenesis of MDS and AML. We previously showed that the Apc -haploinsufficient mice ( Apc del/+ ) model MDS induced by an aberrant BM microenvironment. We sought to determine whether Apc, a multifunctional protein and key negative regulator of the canonical β-catenin (Ctnnb1)/WNT-signaling pathway, mediates this disease through modulating WNT signaling, and whether inhibition of WNT signaling prevents the development of MDS in Apc del/+ mice. Here, we demonstrate that loss of 1 copy of Ctnnb1 is sufficient to prevent the development of MDS in Apc del/+ mice and that altered canonical WNT signaling in the microenvironment is responsible for the disease. Furthermore, the US Food and Drug Administration (FDA)-approved drug pyrvinium delays and/or inhibits disease in Apc del /+ mice, even when it is administered after the presentation of anemia. Other groups have observed increased nuclear CTNNB1 in stromal cells from a high frequency of MDS/AML patients, a finding that together with our results highlights a potential new strategy for treating some myeloid disorders. © 2017 by The American Society of Hematology.

  12. MDS: Recent progress in molecular pathogenesis and clinical aspects. (United States)

    Harada, Hironori


    Myelodysplastic syndromes (MDS) are defined as hematopoietic stem cell disorders caused by various gene abnormalities. Recent analysis using next generation sequencing has provided great progress in identifying relationships between gene mutations and clinical phenotypes of MDS. It is estimated that one or more gene mutations occur in greater than 90% of MDS patients. More than 50 gene mutations affecting RNA splicing machinery, DNA methylation, histone modifications, transcription factors, signal transduction proteins, and components of the cohesion complex participate in the pathogenesis of MDS. The sequential accumulation of additional cooperating mutations drives disease evolution from clonal hematopoiesis of indeterminate potential (CHIP) to symptomatic MDS and from MDS to acute myelogenous leukemia (AML). Mutations in RNA splicing and DNA methylation occur early and are considered founding mutations, whereas others that occur later are regarded as subclonal mutations. RUNX1 mutations are more likely to be subclonal; however, they apparently play a pivotal role in familial MDS. In addition, large alterations of chromosomes are involved in the pathogenesis of MDS. 5q- syndrome, which leads to haploinsufficiency of the located genes, has consistent clinical features. Understanding gene abnormalities of MDS patients can provide clinical information, including diagnosis, prognostic score, and prediction of response to therapy.

  13. Increased separase activity and occurrence of centrosome aberrations concur with transformation of MDS. (United States)

    Ruppenthal, Sabrina; Kleiner, Helga; Nolte, Florian; Fabarius, Alice; Hofmann, Wolf-Karsten; Nowak, Daniel; Seifarth, Wolfgang


    ESPL1/separase, a cysteine endopeptidase, is a key player in centrosome duplication and mitotic sister chromatid separation. Aberrant expression and/or altered separase proteolytic activity are associated with centrosome amplification, aneuploidy, tumorigenesis and disease progression. Since centrosome alterations are a common and early detectable feature in patients with myelodysplastic syndrome (MDS) and cytogenetic aberrations play an important role in disease risk stratification, we examined separase activity on single cell level in 67 bone marrow samples obtained from patients with MDS, secondary acute myeloid leukemia (sAML), de novo acute myeloid leukemia (AML) and healthy controls by a flow cytometric separase activity assay. The separase activity distribution (SAD) value, a calculated measure for the occurrence of cells with prominent separase activity within the analyzed sample, was tested for correlation with the centrosome, karyotype and gene mutation status. We found higher SAD values in bone marrow cells of sAML patients than in corresponding cells of MDS patients. This concurred with an increased incidence of aberrant centrosome phenotypes in sAML vs. MDS samples. No correlation was found between SAD values and the karyotype/gene mutation status. During follow-up of four MDS patients we observed increasing SAD values after transformation to sAML, in two patients SAD values decreased during azacitidine therapy. Cell culture experiments employing MDS-L cells as an in vitro model of MDS revealed that treatment with rigosertib, a PLK1 inhibitor and therapeutic drug known to induce G2/M arrest, results in decreased SAD values. In conclusion, the appearance of cells with unusual high separase activity levels, as indicated by increased SAD values, concurs with the transformation of MDS to sAML and may reflect separase dysregulation potentially contributing to clonal evolution during MDS progression. Separase activity measurement may therefore be useful as a

  14. MDS MIC Catalog Inputs (United States)

    Johnson-Throop, Kathy A.; Vowell, C. W.; Smith, Byron; Darcy, Jeannette


    This viewgraph presentation reviews the inputs to the MDS Medical Information Communique (MIC) catalog. The purpose of the group is to provide input for updating the MDS MIC Catalog and to request that MMOP assign Action Item to other working groups and FSs to support the MITWG Process for developing MIC-DDs.

  15. Study of RpI22 in MDS and AML (United States)


    developed significantly larger and markedly more vascularized thymic tumors than those observed in Rpl22þ/þ control mice. But, unlike Rpl22þ/þ or Rpl22þ...hypoxia (31). Alternatively, we did not observe obvious necrosis in the center of the large thymic tumors from Rpl22-deficent mice, suggesting Rpl22...Orthop Res 2004;22:1175–81. 32. Loeffler S, Fayard B, Weis J, Weissenberger J. Interleukin-6 induces tran- scriptional activation of vascular endothelial

  16. Flow cytometry in the diagnosis of myelodysplastic syndromes (MDS) and the value of myeloid nuclear differentiation antigen (MNDA). (United States)

    Bellos, Frauke; Kern, Wolfgang


    Background: Confirming diagnosis of myelodysplastic syndromes (MDS) is often challenging. Standard diagnostic methods are cytomorphology (CM) and cytogenetics (CG). Multiparameter flow cytometry (MFC) is upcoming in MDS diagnostic work up, comparability and investigator experience are critical. Myeloid nuclear differentiation antigen (MNDA) in myelomonocytic cells might be expressed more weakly in patients with MDS. The analysis of MNDA may thus improve diagnostic capabilities of MFC in MDS. Methods: Staining methods and antibody combinations for MFC in MDS are outlined, giving details for interpretation of results in regard to dyspoiesis. MFC results are correlated with CM and CG and with survival data. Use of myeloid nuclear differentiation antigen (MNDA) in MDS diagnostics was evaluated in 239 patients with MDS, AML, other cytopenic conditions and in 30 negative controls. Results: Strong correlation between findings in CM and MFC was found; MFC results correlated well with those of CG. Patients with higher grades of dysplasia in MFC had shorter overall survival. Percentages of granulocytes and monocytes with diminished MNDA expression (%dimG, %dimM) were higher in patients with MDS and AML. Mean fluorescence intensity (MFI) of MNDA in monocytes was lower in MDS and AML. Cut-off values for %dimG (12%) and %dimM (22%) as well as for MFI in monocytes (72) were defined discriminating between MDS and non-MDS. Conclusion: MFC adds significant information on dyspoiesis in the diagnostic work up for MDS and provides prognostic information. MNDA expression can be assessed by MFC and may facilitate evaluation of dyspoiesis when added to MDS MFC panels. © 2014 Clinical Cytometry Society. Copyright © 2014 Clinical Cytometry Society.

  17. Access/AML - (United States)

    Department of Transportation — The AccessAML is a web-based internet single application designed to reduce the vulnerability associated with several accounts assinged to a single users. This is a...

  18. RUNX1/AML1 point mutations take part in the pathogenesis of radiation-and therapy-related myeloid neoplasms

    International Nuclear Information System (INIS)

    Harada, Yuka; Kimura, Akiro; Harada, Hironori


    High frequency of myelodysplastic syndrome (MDS) has been reported in Hiroshima A-bomb exposed survivors, in resident around Semipalatinsk Nuclear Laboratory and in exposed people by Chernobyl Nuclear Power Station Accident. MDS/acute myeloid leukemia (AML) is thought to be caused by mutation of runt-related transcription factor 1 (RUNX1) gene after a long time post exposure to relatively low dose radiation. In this study, participation of RUNX1/AML1 point mutations was examined in pathogenesis of the title neoplasms experienced in authors' facility. Subjects were 18/417 cases in whom myeloproliferative neoplasms (MPN) had switched to MDS or AML in the follow-up period of 1-25 years, and 11/124 cases in whom t-MN (therapy-related myeloid neoplasms) had developed during the remission of acute promyelocytic leukemia (APL) in the 1-9.7 years follow up. Point mutations were analyzed by PCR-single strand conformation polymorphism (PCR-SSCP) followed by base sequencing. In the former cases above, RUNX1 point mutation was found in 5/18 cases and in the latter, 4/11. When patients with persistent decrease of blood cells post therapy of APL were followed up for mutation, their RUNX1 point mutation was detected before they were diagnosed to be morbid of MDS/AML. The point mutation was thus a biomarker of myelo-hematogenic cancer, and was thought useful for early diagnosis of MDS and AML. (T.T.)

  19. A phase 1/2 study of rigosertib in patients with myelodysplastic syndromes (MDS) and MDS progressed to acute myeloid leukemia. (United States)

    Navada, Shyamala C; Fruchtman, Steven M; Odchimar-Reissig, Rosalie; Demakos, Erin P; Petrone, Michael E; Zbyszewski, Patrick S; Holland, James F; Silverman, Lewis R


    This Phase 1/2, dose-escalating study of rigosertib enrolled 22 patients with higher-risk myelodysplastic syndromes (MDS) (n=9) and acute myeloid leukemia (AML; n=13) who had relapsed or were refractory to standard therapy and for whom no second-line therapies were approved. Patients received 3- to 7-day continuous intravenous infusions of rigosertib, an inhibitor of Ras-effector pathways that interacts with the Ras-binding domains, common to several signaling proteins including Raf and PI3 kinase. Rigosertib was administered at doses of 650-1700mg/m 2 /day in 14-day cycles. Initial dose escalation followed a Fibonacci scheme, followed by recommended phase 2 dose confirmation in an expanded cohort. Rigosertib was well tolerated for up to 23 cycles, with no treatment-related deaths and 18% of patients with related serious adverse events (AEs). Common AEs were fatigue, diarrhea, pyrexia, dyspnea, insomnia, and anemia. Rigosertib exhibited biologic activity, with reduction or stabilization of bone marrow blasts and improved peripheral blood counts in a subset of patients. Ten of 19 evaluable patients (53%) demonstrated bone marrow/peripheral blood responses (n=4 MDS, n=1 AML) or stable disease (n=3 MDS, n=2 AML). Median survival was 15.7 and 2.0 months for responders and non-responders, respectively. Additional studies of rigosertib are ongoing in higher-risk MDS (NCT00854646). Copyright © 2017 Elsevier Ltd. All rights reserved.

  20. Acute myeloid leukemia (AML) - children (United States)

    Acute myeloid leukemia is a cancer of the blood and bone marrow. Bone marrow is the soft tissue inside ... develops quickly. Both adults and children can get acute myeloid leukemia ( AML ). This article is about AML in children.

  1. Strongly-MDS convolutional codes

    NARCIS (Netherlands)

    Gluesing-Luerssen, H; Rosenthal, J; Smarandache, R

    Maximum-distance separable (MDS) convolutional codes have the property that their free distance is maximal among all codes of the same rate and the same degree. In this paper, a class of MDS convolutional codes is introduced whose column distances reach the generalized Singleton bound at the

  2. Outcome of Allogeneic Stem Cell Transplantation for Patients Transformed to Myelodysplastic Syndrome or Leukemia from Severe Aplastic Anemia: A Report from the MDS Subcommittee of the Chronic Malignancies Working Party and the Severe Aplastic Anemia Working Party of the European Group for Blood and Marrow Transplantation

    NARCIS (Netherlands)

    Hussein, A.A.; Halkes, C.M.; Socie, G.; Tichelli, A.; Borne, P.A. von dem; Schaap, M.N.; Foa, R.; Ganser, A.; Dufour, C.; Bacigalupo, A.; Locasciulli, A.; Aljurf, M.; Peters, C.; Robin, M.; Biezen, A.A. van; Volin, L.; Witte, T.J. de; Marsh, J.; Passweg, J.R.; Kroger, N.; et al.,


    One hundred and forty patients who had undergone hematopoietic stem cell transplantation (HSCT) for myelodysplastic syndrome (MDS) or acute myelogenous leukemia (AML) transformation after treatment of severe aplastic anemia (SAA) were identified in the European Group for Blood and Marrow

  3. MDS 3.0 Frequency Report (United States)

    U.S. Department of Health & Human Services — The MDS 3.0 Frequency Report summarizes information for active residents currently in nursing homes. The source of these counts is the residents MDS assessment...

  4. New MDS or near MDS self-dual codes over finite fields


    Tong, Hongxi; Wang, Xiaoqing


    The study of MDS self-dual codes has attracted lots of attention in recent years. There are many papers on determining existence of $q-$ary MDS self-dual codes for various lengths. There are not existence of $q-$ary MDS self-dual codes of some lengths, even these lengths $< q$. We generalize MDS Euclidean self-dual codes to near MDS Euclidean self-dual codes and near MDS isodual codes. And we obtain many new near MDS isodual codes from extended negacyclic duadic codes and we obtain many new M...

  5. Cost-effectiveness of azacitidine compared with low-doses of chemotherapy (LDC in myelodysplastic syndrome (MDS

    Directory of Open Access Journals (Sweden)

    Myrna Candelaria-Hernández


    Full Text Available ABSTRACTIntroductionMyelodysplastic syndrome (MDS comprises a group of clonal hematological disorders, characterized by ineffective hematopoiesis and progressive bone marrow failure. It increases the risk of transformation to acute myeloid leukemia (AML. Therapeutic benefit should include overall survival increase (OS, hematological improvement, transfusion dependence and time to progression to AML decrease.ObjectiveAssess, from a Mexican health-care perspective, the cost-effectiveness of azacitidine compared with low-doses of chemotherapy (LDC plus best supportive care (BSC for the treatment of adult patients with intermediate-2 and high-risk MDS, who are not eligible for hematopoietic stem-cell transplantation. We developed a cost-effectiveness survival analysis model of three stages: MDS, AML, and death. OS and costs are extrapolated beyond three-year time horizon. Discount rate of 5% was applied. To estimate the model cycle probability transition to mortality state, survival curves were constructed for each treatment arm using individual patient-level data from Study AZA-001. Unitary costs are from public price list, and profiles for the management of MDS and AML were collected separately using a structured questionnaire. Probabilistic sensitivity analyses (PSA were conducted by simultaneously sampling from estimated probability distributions of model parameters.ResultsOverall survival was projected to increase by 72.26 weeks with azacitidine. Incremental expected total costs for azacitidine compared to LDC was MXN$68,045. However, the cost of the drug therapy was lower with azacitidine. The incremental cost-effectiveness ratio (ICER for azacitidine compared to LDC was MXN$48,932 per life-year gained (LYG. PSA showed that azacitidine was a highly cost-effective option in 96.49% of the simulated cases in MXN$180,000/LYG willingness-to-pay.ConclusionsCompared with LDC, azacitidine represents a cost-effective treatment alternative in patients

  6. Cytomorphology review of 100 newly diagnosed lower-risk MDS patients in the European LeukemiaNet MDS (EUMDS) registry reveals a high inter-observer concordance. (United States)

    de Swart, Louise; Smith, Alex; MacKenzie, Marius; Symeonidis, Argiris; Neukirchen, Judith; Mikulenková, Dana; Vallespí, Teresa; Zini, Gina; Paszkowska-Kowalewska, Malgorzata; Kruger, Anton; Saft, Leonie; Fenaux, Pierre; Bowen, David; Hellström-Lindberg, Eva; Čermák, Jaroslav; Stauder, Reinhard; Tatic, Aurelia; Holm, Mette Skov; Malcovati, Luca; Mądry, Krzysztof; Droste, Jackie; Blijlevens, Nicole; de Witte, Theo; Germing, Ulrich


    The European LeukemiaNet MDS (EUMDS) registry is collecting data of myelodysplastic syndrome (MDS) patients belonging to the IPSS low or intermediate-1 category, newly diagnosed by local cytologists. The diagnosis of MDS can be challenging, and some data report inter-observer variability with regard to the assessment of the MDS subtype. In order to ensure that correct diagnoses were made by the participating centres, blood and bone marrow slides of 10% of the first 1000 patients were reviewed by an 11-person panel of cytomorphologists. All slides were rated by at least 3 panel members (median 8 panel members; range 3-9). Marrow slides from 98 out of 105 patients were of good quality and therefore could be rated properly according to the WHO 2001 classification, including assessment of dysplastic lineages. The agreement between the reviewers whether the diagnosis was MDS or non-MDS was strong with an intra-class correlation coefficient (ICC) of 0.85. Six cases were detected not to fit the entry criteria of the registry, because they were diagnosed uniformly as CMML or AML by the panel members. The agreement by WHO 2001 classification was strong as well (ICC = 0.83). The concordance of the assessment of dysplastic lineages was substantial for megakaryopoiesis and myelopoiesis and moderate for erythropoiesis. Our data show that in general, the inter-observer agreement was high and a very low percentage of misdiagnosed cases had been entered into the EUMDS registry. Further studies including histomorphology are warranted.

  7. Pediatric MDS: GATA screen the germline. (United States)

    Stieglitz, Elliot; Loh, Mignon L


    In this issue of Blood, Wlodarski and colleagues demonstrate that as many as 72% of adolescents diagnosed with myelodysplastic syndrome (MDS) and monosomy 7 harbor germline mutations in GATA2. Although pediatric MDS is a very rare diagnosis, occurring in 0.8 to 4 cases per million, Wlodarski et al screened >600 cases of primary or secondary MDS in children and adolescents who were enrolled in the European Working Group on MDS consortium over a period of 15 years. The overall frequency of germline GATA2 mutations in children with primary MDS was 7%, and 15% in those presenting with advanced disease. Notably, mutations in GATA2 were absent in patients with therapy-related MDS or acquired aplastic anemia.

  8. AML (Logistics Center) Local Area Network - (United States)

    Department of Transportation — The AML LAN is designed to facilitate the services and resources needed to support the operations of the FAA Logistics Center users. The AML LAN provides support for...

  9. Survey of expert opinions and related recommendations regarding bridging therapy using hypomethylating agents followed by allogeneic transplantation for high-risk MDS. (United States)

    Sohn, Sang Kyun; Moon, Joon Ho


    According to current guidelines on therapeutic strategies for myelodysplastic syndrome (MDS), cytoreductive therapies before allogeneic stem cell transplantation (SCT) are not widely recommended for patients with high-risk MDS or refractory anemia with excess blasts (RAEB) who are eligible for allogeneic SCT because of controversial evidence on the role of such therapies. Yet, while treatment with hypomethylating agents (HMAs) has a critical limitation in eradicating MDS clones, the use of HMA treatment as a bridge to allogeneic SCT has become a focus with the hope of improving the SCT outcome based on the chance of achieving complete remission or reducing the blast percentage safely and effectively before allogeneic SCT. However, a consensus needs to be established on the use of HMAs as a bridging therapy for high-risk MDS or RAEB. Thus, the Korean AML/MDS working party group surveyed 34 Korean MDS experts on their bridging therapies for high-risk MDS. Accordingly, this paper presents the survey questionnaire and resulting data, along with a summary of the consensus and related recommendations regarding strategies using HMA treatment and allogeneic SCT based on reported studies and the current survey results. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  10. Long Term Care Minimum Data Set (MDS) (United States)

    U.S. Department of Health & Human Services — The Long-Term Care Minimum Data Set (MDS) is a standardized, primary screening and assessment tool of health status that forms the foundation of the comprehensive...

  11. Hypotéza o MDS kódech


    Kesely, Michal


    In this thesis, we study some properties of MDS codes and we mainly focus on the MDS codes conjecture. In the first chapter we define MDS codes, show some examples and basic properties of MDS codes, for example a link between MDS codes and Latin squares or rectangles. Afterwards we state the MDS codes conjecture and prove it in several cases. In the third chapter we can observe the relationship between MDS codes and narcs in projective geometries. Finally we present those known cases, for whi...

  12. Iron overload in myelodysplastic syndromes (MDS). (United States)

    Gattermann, Norbert


    Iron overload (IOL) starts to develop in MDS patients before they become transfusion-dependent because ineffective erythropoiesis suppresses hepcidin production in the liver and thus leads to unrestrained intestinal iron uptake. However, the most important cause of iron overload in MDS is chronic transfusion therapy. While transfusion dependency by itself is a negative prognostic factor reflecting poor bone marrow function, the ensuing transfusional iron overload has an additional dose-dependent negative impact on the survival of patients with lower risk MDS. Cardiac dysfunction appears to be important in this context, as a consequence of chronic anemia, age-related cardiac comorbidity, and iron overload. Another potential problem is iron-related endothelial dysfunction. There is some evidence that with increasing age, high circulating iron levels worsen the atherosclerotic phenotype. Transfusional IOL also appears to aggravate bone marrow failure in MDS, through unfavorable effects on mesenchymal stromal cells as well a hematopoietic cells, particularly erythroid precursors. Patient series and clinical trials have shown that the iron chelators deferoxamine and deferasirox can improve hematopoiesis in a minority of transfusion-dependent patients. Analyses of registry data suggest that iron chelation provides a survival benefit for patients with MDS, but data from a prospective randomized clinical trial are still lacking.

  13. Explicit MDS Codes with Complementary Duals

    DEFF Research Database (Denmark)

    Beelen, Duals Peter; Jin, Lingfei


    In 1964, Massey introduced a class of codes with complementary duals which are called Linear Complimentary Dual (LCD for short) codes. He showed that LCD codes have applications in communication system, side-channel attack (SCA) and so on. LCD codes have been extensively studied in literature....... On the other hand, MDS codes form an optimal family of classical codes which have wide applications in both theory and practice. The main purpose of this paper is to give an explicit construction of several classes of LCD MDS codes, using tools from algebraic function fields. We exemplify this construction...

  14. PP2A: The Achilles Heal in MDS with 5q Deletion

    Directory of Open Access Journals (Sweden)

    David eSallman


    Full Text Available Myelodysplastic syndromes (MDS represent a hematologically diverse group of myeloid neoplasms, however, one subtype characterized by an isolated deletion of chromosome 5q (del(5q is pathologically and clinically distinct. Patients with del(5q MDS share biological features that account for the profound hypoplastic anemia and unique sensitivity to treatment with lenalidomide. Ineffective erythropoiesis in del(5q MDS arises from allelic deletion of the ribosomal processing S-14 (RPS14 gene, which leads to MDM2 sequestration with consequent p53 activation and erythroid cell death. Since its approval in 2005, lenalidomide has changed the natural course of the disease. Patients who achieve transfusion independence and/or a cytogenetic response with lenalidomide have a decreased risk of progression to AML and an improved overall survival compared to non-responders. Elucidation of the mechanisms of action of lenalidomide in del(5q MDS has advanced therapeutic strategies for this disease. The selective cytotoxicity of lenalidomide in del(5q clones derives from inhibition of a haplodeficient phosphatase whose catalytic domain is encoded within the common deleted region on chromosome 5q, i.e., protein phosphatase 2A (PP2Acα. PP2A is a highly conserved, dual specificity phosphatase that plays an essential role in regulation of the G2/M checkpoint. Inhibition of PP2Acα results in cell cycle arrest and apoptosis in del(5q cells. Targeted knockdown of PP2Acα using siRNA is sufficient to sensitize non-del(5q clones to lenalidomide. Through its inhibitory effect on PP2A, lenalidomide stabilizes MDM2 to restore p53 degradation in erythroid precursors, with subsequent arrest in G2/M. Unfortunately, the majority of patients with del(5q MDS develop resistance to lenalidomide over time associated with PP2Acα overexpression. Targeted inhibition of PP2A with a more potent inhibitor has emerged as an attractive therapeutic approach for patients with del(5q MDS.

  15. Utility of 5-Methylcytosine Immunohistochemical Staining to Assess Global DNA Methylation and Its Prognostic Impact in MDS Patients (United States)

    Chandra, Dinesh; Tyagi, Seema; Singh, Jasdeep; Deka, Roopam; Manivannan, Prabhu; Mishra, Pravas; Pati, Hara Prasad; Saxena, Renu


    Background: DNA methylation plays a vital role in the pathogenesis of the myelodysplastic syndrome (MDS), a heterogeneous group of clonal hematopoietic stem cell (HSC) disorders. It is reported to be an independent prognostic factor affecting overall survival (OS). Our aim was to analyze the role of global DNA methylation using an anti-5-methylcytosine (5-MC) antibody by immunohistochemistry (IHC) of bone marrow biopsy (BM Bx) specimens in MDS patients, assessing correlations with various clinical and biological prognostic factors. Material and methods: A total of 59 MDS cases, classified as per the World Health Organization (WHO) 2008 guidelines, were evaluated over a period of 4 years. Clinical data were retrieved from departmental case records and anti-5-MC expression was analyzed with formalin fixed paraffin embedded sections of BM Bx specimens of MDS patients and controls. Results: The median age at diagnosis was 52 years (15-85years). Patients were categorized into low risk (59%) and high risk (41%) according to International Prognostic Scoring System (IPSS). The median follow-up time was 10 months (1 to 37 months). We generated a methylation score (M-score) using anti-5-MC and with the derived cut-off of 30.5 from the receiver operator curve (ROC), there was a significant difference between the two groups in the percentage of BM blasts (p=0.01), WHO sub-type (p=0.01), IPSS (p=0.004), progression to AML (p=0.04) on univariate analysis. Interestingly, patients showing a high M-score (M-score ≥ 30.5) demonstrated a significantly shorter OS and progression to AML. However, on multivariate analysis, only BM blasts (p=0.01) and IPSS (p=0.02) remained independent variables for progression to AML and OS respectively. Conclusion: Immunostaining with anti-5-MC antibody with BM Bx samples is a simple and cost effective technique to detect global methylation, a powerful tool to predict overall survival in patients with MDS. Creative Commons Attribution License

  16. Lessons from the atomic bomb about secondary MDS. (United States)

    Hata, Tomoko; Imanishi, Daisuke; Miyazaki, Yasushi


    Myelodysplastic syndromes (MDSs) is a hematological neoplasm defined by ineffective hematopoiesis, dysplasia of hematopoietic cells, and risk of progression to acute leukemia. MDS occurs as de novo or secondary, and chemoradiotherapy for cancers is thought to increase the risk of MDS among patients. Recently, an epidemiological study for MDS among A-bomb survivors was performed, and it clearly demonstrated that the exposure to external radiation significantly increased the risk of MDS. Precise epidemiological data among survivors have revealed important clinical factors related to the risk of leukemias. In this review, by comparing data for secondary MDS and leukemia/MDS among survivors, several factors which would affect the risk of MDS, especially secondary MDS, are discussed.

  17. Osteolytic Bone Lesions - A Rare Presentation of AML M6. (United States)

    Geetha, N; Sreelesh, K P; Priya, M J; Lali, V S; Rekha, N


    Acute myeloid leukemia (AML) M6 is a rare form of AML accounting for M6 before. We discuss the case of a 17 year old boy with AML M6, who presented with osteolytic lesion of right humerus. He was treated with induction and consolidation chemotherapy. The present case is the first report in literature of AML M6 presenting with skeletal lesions.

  18. Unraveling the Pathogenesis of MDS: The NLRP3 Inflammasome and Pyroptosis Drive the MDS Phenotype. (United States)

    Sallman, David A; Cluzeau, Thomas; Basiorka, Ashley A; List, Alan


    Myelodysplastic syndromes (MDS) are characterized by bone marrow cytological dysplasia and ineffective hematopoiesis in the setting of recurrent somatic gene mutations and chromosomal abnormalities. The underlying pathogenic mechanisms that drive a common clinical phenotype from a diverse array of genetic abnormalities have only recently begun to emerge. Accumulating evidence has highlighted the integral role of the innate immune system in upregulating inflammatory cytokines via NF-κB activation in the pathogenesis of MDS. Recent investigations implicate activation of the NLRP3 inflammasome in hematopoietic stem/progenitor cells as a critical convergence signal in MDS with consequent clonal expansion and pyroptotic cell death though caspase-1 maturation. Specifically, the alarmin S100A9 and/or founder gene mutations trigger pyroptosis through the generation of reactive oxygen species leading to assembly and activation of the redox-sensitive NLRP3 inflammasome and β-catenin, assuring propagation of the MDS clone. More importantly, targeted inhibition of varied steps in this pathway restore effective hematopoiesis. Together, delineation of the role of pyroptosis in the clinical phenotype of MDS patients has identified novel therapeutic strategies that offer significant promise in the treatment of MDS.

  19. Red Blood Cell Transfusion Dependency and Hyperferritinemia Are Associated with Impaired Survival in Patients Diagnosed with Myelodysplastic Syndromes: Results from the First Polish MDS-PALG Registry. (United States)

    Waszczuk-Gajda, Anna; Mądry, Krzysztof; Machowicz, Rafał; Drozd-Sokołowska, Joanna; Stella-Hołowiecka, Beata; Mital, Andrzej; Obara, Agata; Szmigielska-Kapłon, Anna; Sikorska, Anna; Subocz, Edyta; Jędrzejczak, Wiesław W; Dwilewicz-Trojaczek, Jadwiga


    Myelodysplastic syndromes (MDS) are a heterogeneous group of clonal stem cell disorders characterized by ineffective hematopoiesis, cytopenias and a risk of progression to acute myeloid leukemia (AML). Anemia is the most frequent cytopenia diagnosed in patients with MDS. Regular RBC transfusions are the only treatment option for about 40% of patients. Transfusion-dependent patients develop secondary iron overload. The influence of serum ferritin (SF) concentration on survival and acute myeloid leukemia transformation in MDS patients remains controversial. The data for the Central European population is scarce and so far there is no description for Poland. The aim of this study was to perform a retrospective analysis of the relationship of SF concentration with red blood cell transfusion dependency, survival and transformation to acute myeloid leukemia. We retrospectively evaluated the data of the 819 MDS patients (58% male; median age 70 years) included in the MDS Registry of the MDS Section of the Polish Adult Leukemia Group (PALG). Analyses were performed on 190 patients diagnosed with MDS, maximal 6 months before inclusion to the registry in order to avoid selection bias (a shorter survival of higher risk MDS patients). Patients with hyperferritinemia higher than 1000 ng/L vs. patients with SF concentration lower than 1000 ng/L had a median survival of 320 days vs. 568 days, respectively (p log-rank = 0.014). The following factors were found to significantly worsen survival: RBC-transfusion dependence (p = 0.0033; HR 2.67L), platelet transfusion dependence (p = 0.0071; HR 3.321), hemoglobin concentration lower than 10 g/dL (p = 0.0036; HR 2.97), SF concentration higher than 1000 ng/L (p = 0.0023; HR = 2.94), platelet count lower than 10 G/L (p = 0.0081 HR = 5.04), acute leukemia transformation (p = 0.0081; HR 1.968). Taking into account the relatively low number of patients in previous studies exploring hyperferritinemia in MDS, the results of the first Polish

  20. MDS Nordion - a Canadian success story

    International Nuclear Information System (INIS)

    Boyd, F.


    MDS Nordion,the world leading supplier of radioisotopes, had its beginnings as a small division of the crown company Eldorado Mining and Refining Ltd. in the late 1940's. With the end of World War II, Eldorado found itself with a supply of radium left over from the production of uranium during the war and set up a small group in Ottawa to sell it. Most of the stock of radium was disposed of when the development of the NRX reactor made reactor produced radioisotopes possible. The company turned to selling these radioisotopes and soon focused on Cobalt 60 for its use in cancer therapy. In 1952, the group transferred to AECL (Atomic Energy of Canada Ltd.), as part of the Commercial Products Division. In 1988, as part of the federal government's move to privatization, the organization was split into two companies, Theratronics, which manufactures the cancer therapy machines and other equipment for the use of radioisotopes, and Nordion International, which continued the primary business of processing, packaging, selling radioisotopes. In 1991 Nordion International was sold to MDS Inc., a large international group of companies in the life and sciences fields with headquarters in Toronto. The name was changed to MDS Nordion in December 1996


    Directory of Open Access Journals (Sweden)

    Robert Gale


    Full Text Available Therapy-related leukemia or therapy-related myeloid neoplasm are widely-used terms to designate leukemia developing in persons who previously received anti-cancer therapy (for example, see references 1, 2, especially if the prior anti-cancer therapy included drugs such as alkylators, DNA-intercalators, topoisomerase-2-inhibitors, purines and/or ionizing radiations.   Sometimes specific genes such as AML1, EVI1, NRAS or MLL are mutated by therapy or gene variants are produced which activate mutagens or interfere with DNA repair, such FANC, NQ01 or AML2. 3-5   But how can we know if AML in someone is a therapy-related? Keywords: Therapy-related leukemia; alkylators; ionizing radiations; Topoisomerase Inhibitors; DNA Repair

  2. Downregulation of MMP1 in MDS-derived mesenchymal stromal cells reduces the capacity to restrict MDS cell proliferation. (United States)

    Zhao, Sida; Zhao, Youshan; Guo, Juan; Fei, Chengming; Zheng, Qingqing; Li, Xiao; Chang, Chunkang


    The role of mesenchymal stromal cells (MSCs) in the pathogenesis of myelodysplastic syndromes (MDS) has been increasingly addressed, but has yet to be clearly elucidated. In this investigation, we found that MDS cells proliferated to a greater extent on MDS-derived MSCs compared to normal MSCs. Matrix metalloproteinase 1(MMP1), which was downregulated in MDS-MSCs, was identified as an inhibitory factor of MDS cell proliferation, given that treatment with an MMP1 inhibitor or knock-down of MMP1 in normal MSCs resulted in increased MDS cell proliferation. Further investigations indicated that MMP1 induced apoptosis of MDS cells by interacting with PAR1 and further activating the p38 MAPK pathway. Inhibition of either PAR1 or p38 MAPK can reverse the apoptosis-inducing effect of MMP1. Taken together, these data indicate that downregulation of MMP1 in MSCs of MDS patients may contribute to the reduced capacity of MSCs to restrict MDS cell proliferation, which may account for the malignant proliferation of MDS cells.

  3. AML (Advanced Mud Logging: First Among Equals

    Directory of Open Access Journals (Sweden)

    T. Loermans


    Full Text Available During the past ten years an enormous development in mud logging technology has been made. Traditional mud logging was only qualitative in nature, and mudlogs could not be used for the petrophysical well evaluations which form the basis for all subsequent activities on wells and fields. AML however can provide quantitative information, logs with a reliability, trueness and precision like LWD and WLL. Hence for well evaluation programmes there are now three different logging methods available, each with its own pros and cons on specific aspects: AML, LWD and WLL. The largest improvements have been made in mud gas analysis and elemental analysis of cuttings. Mud gas analysis can yield hydrocarbon fluid composition for some components with a quality like PVT analysis, hence not only revolutionising the sampling programme so far done with only LWD/WLL, but also making it possible to geosteer on fluid properties. Elemental analysis of cuttings, e.g. with XRF, with an ability well beyond the capabilities of the spectroscopy measurements possible earlier with LWD/WLL tools, is opening up improved ways to evaluate formations, especially of course where the traditional methods are falling short of requirements, such as in unconventional reservoirs. An overview and specific examples of these AML logs is given, from which it may be concluded that AML now ought to be considered as “first among its equals”.

  4. Management of older adults with myelodysplastic syndromes (MDS). (United States)

    Luskin, Marlise R; Abel, Gregory A


    The myelodysplastic syndromes (MDS) are a varied group of hematologic neoplasms that lead to bone marrow failure, and also carry a risk of progression to acute myeloid leukemia. Patients with MDS suffer significant impairments to both their quality of life and survival. Age is the dominant risk factor for the development of MDS, with a median age at diagnosis over 70years. Consequently, patients with MDS frequently have concurrent comorbidities and/or frailty which may be coincident or related to the disease itself. Disease characteristics, degree of comorbidity, and presence of frailty all impact prognosis. Treatment of MDS focuses on supportive care, with disease-modifying approaches (chemotherapy and allogeneic hematopoietic cell transplantation) reserved for fit patients with high-risk disease. Care of patients with MDS requires understanding the disease in the context of an older population, and tailoring approaches to both disease risk and patient suitability for therapy. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. Construction of new quantum MDS codes derived from constacyclic codes (United States)

    Taneja, Divya; Gupta, Manish; Narula, Rajesh; Bhullar, Jaskaran

    Obtaining quantum maximum distance separable (MDS) codes from dual containing classical constacyclic codes using Hermitian construction have paved a path to undertake the challenges related to such constructions. Using the same technique, some new parameters of quantum MDS codes have been constructed here. One set of parameters obtained in this paper has achieved much larger distance than work done earlier. The remaining constructed parameters of quantum MDS codes have large minimum distance and were not explored yet.

  6. Are the MDS-UPDRS-based composite scores clinically applicable? (United States)

    Makkos, Attila; Kovács, Márton; Aschermann, Zsuzsanna; Harmat, Márk; Janszky, József; Karádi, Kázmér; Kovács, Norbert


    The International Parkinson and Movement Disorder Society-sponsored UPDRS (MDS-UPDRS) is a powerful clinical outcome measure. To evaluate the feasibility of various MDS-UPDRS-based composite scores and determine their minimal clinically important difference threshold values. Overall, 1,113 paired investigations of 452 patients were reviewed implementing three different techniques simultaneously. Based on the ordinal regression modeling, the MDS-UPDRS II+III, MDS-UPDRS I+II+III, and the total score of MDS-UPDRS are clinically applicable outcome measures. Any improvement greater than 4.9 points or any worsening more than 4.2 points on MDS-UPDRS II+III represent a minimal, yet clinically meaningful, change. In reference to MDS-UPDRS I+II+III, the smallest changes considered clinically relevant were 6.7 and 5.2 points for improvement and deterioration, respectively. The thresholds for the total score of MDS-UPDRS were 7.1 points for improvement and 6.3 points for worsening. Our findings support the application of various MDS-UPDRS-based composite scores. © 2018 International Parkinson and Movement Disorder Society. © 2018 International Parkinson and Movement Disorder Society.

  7. Treatment strategies in patients with AML or high-risk myelodysplastic syndrome relapsed after Allo-SCT. (United States)

    Sauer, T; Silling, G; Groth, C; Rosenow, F; Krug, U; Görlich, D; Evers, G; Albring, J; Besoke, R; Mesters, R M; Müller-Tidow, C; Kessler, T; Büchner, T; Berdel, W E; Stelljes, M


    Non-relapse mortality after Allo-SCT has significantly decreased over the last years. Nevertheless, relapse remains a major cause for post SCT mortality in patients with AML and high-risk myelodysplastic syndrome (MDS). In this retrospective single-center analysis, we have analyzed the treatment outcomes of 108 patients with AML or MDS, who relapsed after Allo-SCT. Seventy of these patients (65%) were treated with salvage therapies containing chemotherapy alone, allogeneic cell-based treatment or the combination of both. Thirty-eight patients (35%) received palliative treatment. Median OS after diagnosis of relapse was 130 days. Compared with patients who received chemotherapy alone, response to salvage therapy was significantly improved in patients treated with a combination of chemo- and allogeneic cell-based therapy (CR rate 57% vs 13%, P=0.002). Among risk factors concerning pretreatment characteristics, disease status before first Allo-SCT, and details of transplantation, only the time interval from Allo-SCT to relapse was an independent predictor of response to salvage therapy and OS. These data confirmed that time to relapse after transplantation is an important prognostic factor. Up to now, only patients eligible for treatment regimens containing allogeneic cell-based interventions achieved relevant response rates.

  8. MDS classification is improving in an era of the WHO 2016 criteria of MDS: A population-based analysis among 9159 MDS patients diagnosed in the Netherlands. (United States)

    Dinmohamed, Avinash G; Visser, Otto; Posthuma, Eduardus F M; Huijgens, Peter C; Sonneveld, Pieter; van de Loosdrecht, Arjan A; Jongen-Lavrencic, Mojca


    Morphologic and cytogenetic assessments are required to characterize diagnostic and prognostic features of myelodysplastic syndromes (MDS). We assessed whether these assessments were performed among newly diagnosed MDS patients in the Netherlands. MDS cases were retrieved from the nationwide Netherlands Cancer Registry (N=9159; period 2001-2014) and the regional PHAROS MDS registry (N=676; period 2008-2011). The proportion of unclassified MDS decreased from 58% in 2001 to 13% in 2014. Data from the more detailed PHAROS registry revealed that the degree of bone marrow dysplasia was only reported in ∼30% of all evaluable bone marrow aspirates. Further, the International Prognostic Scoring System was undetermined in 55% of patients, primarily owing to unperformed cytogenetics in 46% of patients. The classification of MDS is improving in the Netherlands. Nevertheless, particular diagnostic and prognostic procedures that are essential for the diagnosis and subsequent treatment decision-making of MDS were not fully utilized in particular patient subsets. Copyright © 2017 Elsevier Ltd. All rights reserved.

  9. Design and rationale of the QUAZAR Lower-Risk MDS (AZA-MDS-003) trial: a randomized phase 3 study of CC-486 (oral azacitidine) plus best supportive care vs placebo plus best supportive care in patients with IPSS lower-risk myelodysplastic syndromes and poor prognosis due to red blood cell transfusion-dependent anemia and thrombocytopenia. (United States)

    Garcia-Manero, Guillermo; Almeida, Antonio; Giagounidis, Aristoteles; Platzbecker, Uwe; Garcia, Regina; Voso, Maria Teresa; Larsen, Stephen R; Valcarcel, David; Silverman, Lewis R; Skikne, Barry; Santini, Valeria


    CC-486 is an oral formulation of the epigenetic modifier azacitidine. In an expanded phase 1 trial, CC-486 demonstrated clinical and biological activity in patients with International Prognostic Scoring System (IPSS) lower-risk (low- and intermediate-1-risk) myelodysplastic syndromes (MDS) with poor prognostic features including anemia and/or thrombocytopenia who may have required red blood cell or platelet transfusions. The overall response rate was 40 %, including hematologic improvement in 28 % of patients and RBC transfusion independence sustained for 56 days in 47 % of patients with baseline transfusion dependence. Based on the results of this study, the randomized, placebo-controlled phase 3 QUAZAR Lower-Risk MDS trial (AZA-MDS-003) was initiated. The design and rationale for this trial comparing CC-486 with placebo for the treatment of patients with IPSS lower-risk MDS with poor prognostic features are described. Patients must have IPSS lower-risk MDS with red blood cell (RBC) transfusion-dependent anemia and thrombocytopenia. Eligible patients are randomized 1:1 to receive 300 mg of CC-486 or placebo once daily for the first 21 days of 28-day treatment cycles. Disease status assessments occur at the end of cycle 6 and patients may continue to receive treatment unless there is evidence of progressive disease, lack of efficacy, or unacceptable toxicity. The primary endpoint is RBC transfusion independence for ≥ 84 days, assessed according to International Working Group 2006 criteria. Secondary endpoints include overall survival, hematologic response including platelet response and erythroid response, RBC transfusion independence for ≥ 56 days, duration of RBC transfusion independence, time to RBC transfusion independence, rate of acute myeloid leukemia (AML) progression, time to AML progression, clinically significant bleeding events, safety, health-related quality of life, and healthcare resource utilization. This study will provide data

  10. Distinct mutation profile and prognostic relevance in patients with hypoplastic myelodysplastic syndromes (h-MDS). (United States)

    Yao, Chi-Yuan; Hou, Hsin-An; Lin, Tzung-Yi; Lin, Chien-Chin; Chou, Wen-Chien; Tseng, Mei-Hsuan; Chiang, Ying-Chieh; Liu, Ming-Chih; Liu, Chia-Wen; Kuo, Yuan-Yeh; Wu, Shang-Ju; Liao, Xiu-Wen; Lin, Chien-Ting; Ko, Bor-Shen; Chen, Chien-Yuan; Hsu, Szu-Chun; Li, Chi-Cheng; Huang, Shang-Yi; Yao, Ming; Tang, Jih-Luh; Tsay, Woei; Liu, Chieh-Yu; Tien, Hwei-Fang


    Myelodysplastic syndromes (MDS) are a heterogeneous group of hematologic malignancies. Although most MDS patients have normal or increased BM cellularity (NH-MDS), some have hypocellular BM (h-MDS). The reports concerning the differences in genetic alterations between h-MDS and NH-MDS patients are limited. In this study, 369 MDS patients diagnosed according to the WHO 2008 criteria were recruited. h-MDS patients had lower PB white blood cell and blast counts, and lower BM blast percentages, than those with NH-MDS. h-MDS was closely associated with lower-risk MDS, defined by the International Prognostic Scoring System (IPSS) and revised IPSS (IPSS-R). IPSS-R could properly predict the prognosis in h-MDS (PMDS patients. The h-MDS patients had lower incidences of RUNX1, ASXL1, DNMT3A, EZH2 and TP53 mutations than NH-MDS patients. The cumulated incidence of acute leukemic transformation at 5 years was 19.3% for h-MDS and 40.4% for NH-MDS patients (P= 0.001). Further, the patients with h-MDS had longer overall survival (OS) than those with NH-MDS (P= 0.001), and BM hypocellularity remains an independent favorable prognostic factor for OS irrespective of age, IPSS-R, and gene mutations. Our findings provide evidence that h-MDS indeed represent a distinct clinico-biological subgroup of MDS and can predict better leukemia-free survival and OS.

  11. Hypomethylation and up-regulation of PD-1 in T cells by azacytidine in MDS/AML patients

    DEFF Research Database (Denmark)

    Ørskov, Andreas D; Treppendahl, Marianne B; Skovbo, Anni


    receptor PD-1 is regulated by DNA methylation. In 12 of 27 patients (44%) PD-1 promoter demethylation was observed in sorted peripheral blood T cells isolated over consecutive cycles of treatment with 5-azacytidine (5-aza). The PD-1 promoter demethylation correlated with an increase in PD-1 expression...... HMA treatment can be a possible resistance mechanism, which may be overcome by combination therapy with a PD-1 pathway inhibitor....

  12. Construction of MDS self-dual codes from orthogonal matrices


    Shi, Minjia; Sok, Lin; Solé, Patrick


    In this paper, we give algorithms and methods of construction of self-dual codes over finite fields using orthogonal matrices. Randomization in the orthogonal group, and code extension are the main tools. Some optimal, almost MDS, and MDS self-dual codes over both small and large prime fields are constructed.

  13. The drift-flux correlation package MDS

    International Nuclear Information System (INIS)

    Hoeld, A.


    Based on the SONNENBURG drift-flux correlation, developed at GRS/Garching (Germany), a comprehensive drift-flux correlation package (MDS) has been established. Its aim is to support thermal-hydraulic mixture-fluid models, models being used for the simulation of the steady state and transient behaviour of characteristic thermal-hydraulic parameters of single- or two-phase fluids flowing along coolant channels of different types (being, e.g., parts of NPP-s, steam generators etc.). The characteristic properties of this package with respect to the behaviour at co- and counter-current flow, its inverse solutions needed for steady state simulations, its behaviour when approaching the lower or upper boundary of a two-phase region, its verification and behaviour with respect to other correlations will be discussed. An adequate driver code, MDSDRI, has been established too, allowing to test the package very thoroughly out of the complex thermal-hydraulic codes. (author)

  14. The drift-flux correlation package MDS

    Energy Technology Data Exchange (ETDEWEB)

    Hoeld, A. [Bernaysstr. 16A, Munich, F.R. (Germany)


    Based on the SONNENBURG drift-flux correlation, developed at GRS/Garching (Germany), a comprehensive drift-flux correlation package (MDS) has been established. Its aim is to support thermal-hydraulic mixture-fluid models, models being used for the simulation of the steady state and transient behaviour of characteristic thermal-hydraulic parameters of single- or two-phase fluids flowing along coolant channels of different types (being, e.g., parts of NPP-s, steam generators etc.). The characteristic properties of this package with respect to the behaviour at co- and counter-current flow, its inverse solutions needed for steady state simulations, its behaviour when approaching the lower or upper boundary of a two-phase region, its verification and behaviour with respect to other correlations will be discussed. An adequate driver code, MDSDRI, has been established too, allowing to test the package very thoroughly out of the complex thermal-hydraulic codes. (author)

  15. An Exercise in Extrapolation: Clinical Management of Atypical CML, MDS/MPN-Unclassifiable, and MDS/MPN-RS-T. (United States)

    Talati, Chetasi; Padron, Eric


    According to the recently published 2016 World Health Organization (WHO) classification of myeloid malignancies, myelodysplastic/myeloproliferative neoplasms (MDS/MPN) include atypical chronic myeloid leukemia (aCML), MDS/MPN-unclassifiable (MDS/MPN-U), chronic myelomonocytic leukemia (CMML), juvenile myelomonocytic leukemia (JMML), and MDS/MPN ring sideroblasts with thrombocytosis (MDS/MPN-RS-T). MDS/MPN-RS-T was previously a provisional category known as refractory anemia with ring sideroblasts with thrombocytosis (RARS-T) which has now attained a distinct designation in the 2016 WHO classification. In this review, we focus on biology and management of aCML, MDS/MPN-U, and MDS/MPN-RS-T. There is considerable overlap between these entities which we attempt to further elucidate in this review. We also discuss recent advances in the field of molecular landscape that further defines and characterizes this heterogeneous group of disorders. The paucity of clinical trials available secondary to unclear pathogenesis and rarity of these diseases makes the management of these entities clinically challenging. This review summarizes some of the current knowledge of the molecular pathogenesis and suggested treatment guidelines based on the available data.

  16. Diagnosis, management and response criteria of iron overload in myelodysplastic syndromes (MDS): updated recommendations of the Austrian MDS platform. (United States)

    Valent, Peter; Stauder, Reinhard; Theurl, Igor; Geissler, Klaus; Sliwa, Thamer; Sperr, Wolfgang R; Bettelheim, Peter; Sill, Heinz; Pfeilstöcker, Michael


    Despite the availability of effective iron chelators, transfusion-related morbidity is still a challenge in chronically transfused patients with myelodysplastic syndromes (MDS). In these patients, transfusion-induced iron overload may lead to organ dysfunction or even organ failure. In addition, iron overload is associated with reduced overall survival in MDS. Areas covered: During the past 10 years, various guidelines for the management of MDS patients with iron overload have been proposed. In the present article, we provide our updated recommendations for the diagnosis, prevention and therapy of iron overload in MDS. In addition, we propose refined treatment response criteria. As in 2006 and 2007, recommendations were discussed and formulated by participants of our Austrian MDS platform in a series of meetings in 2016 and 2017. Expert commentary: Our updated recommendations should support early recognition of iron overload, optimal patient management and the measurement of clinical responses to chelation treatment in daily practice.

  17. Progress in the diagnosis of and therapy for MDS. (United States)

    Nannya, Yasuhito


    The WHO classification system of MDS 4 th edition was recently updated. This revision includes nomenclature changes, reflecting the policy of the revision team to emphasize morphological features over cytopenias. Other changes are 1) taking SF3B1 mutation status into account for the definition criteria of MDS-RS (ring sideroblasts), 2) allowing for one additional cytogenetic abnormality (excluding -7/del (7q)) to be diagnosed as 'MDS with isolated del (5q)', 3) sub-classifying MDS-U according to the reasons for being included in this category, and 4) changing the diagnostic rules for myeloid neoplasms with erythroid blast predominance. This session also deals with recent topics in hematopoietic stem cell transplantation (HSCT) as an example of progress in therapy for MDS. Although HSCT is the only curative therapy for MDS, high treatment related mortality precludes its applicability especially for elderly patients, for whom demethylating agents are an alternative. Recently, reports on both well-designed retrospective or prospective studies have validated the advantage of HSCT over demethylating agents for patients of comparatively advanced age with higher risk MDS. Optimal intensity of conditioning regimens for HSCT is another controversial topic for which preliminary results of randomized controlled trials have been released and will be introduced in this session.

  18. MDS clinical diagnostic criteria for Parkinson's disease in China. (United States)

    Li, Jun; Jin, Miao; Wang, Li; Qin, Bin; Wang, Kang


    The Movement Disorder Society Clinical Diagnostic Criteria for Parkinson's disease (MDS-PD Criteria) was introduced by the Movement Disorder Society in 2015 for research purposes. However, its use for clinical diagnosis of Parkinson disease still needs further revision. This study compares the UK-Criteria versus MDS-PD Criteria in the clinical diagnosis of Parkinson disease referred to the China-Japan Friendship Hospital of Beijing, China. To compare the MDS-PD Criteria with the UK-Criteria and discuss the feasibility of the clinical application of MDS-PD Criteria as a general guide to clinical diagnosis of PD in Chinese PD patients. 150 patients of neurology clinic of China-Japan Friendship Hospital of Beijing were recruited in our research. They were divided into three groups: UK-Criteria group, MDS-PD Criteria group and a combined group of UK and MDS-PD Criteria. Clinical history was collected while physical and auxiliary examinations were done by a trained neurologist according to the corresponding criteria. An interrater reliability analysis using the Kappa statistic claimed substantial agreement (κ = 0.626) between the MDS-PD Criteria and the UK-Criteria. The differences between the diagnostic results of these two criteria were statistically significant by paired Chi-square test (p = 0.000). It was found that levodopa-induced dyskinesia had a good positive predictive value, while early bulbar impairment and inspiratory dysfunction presented a negative predictive value. The MDS-PD Criteria emphasize the importance of non-motor symptoms, keeping the motor symptoms as the core for the clinical diagnosis of PD, and establish categories of diagnosis features and levels of certainty which are more complete and organized to be used and replicated by non specialized physicians to evaluated patients with Parkinsonism. The higher sensitivity of MDS-PD Criteria compared with UK-Criteria is worth being widely used in clinical work.

  19. MDS. A disease with high radiation-risk

    International Nuclear Information System (INIS)

    Ban, Sadayuki; Sudo, Hitomi; Saegusa, Kumiko; Sagara, Masashi; Imai, Takashi


    A preliminary epidemiological study demonstrated that myelodysplastic syndrome (MDS) has an excess relative risk per sievert of 13 in atomic bomb survivors. MDS is the only other radiogenic blood disease apart from leukemia. Clinically, MDS involves dysplastic hematopoiesis and an increased risk of leukemic transformation. Because it is uncertain whether MDS pathogenesis affects lymphoid progenitor cells as well as myeloid progenitor cells, we investigated the micronucleus (MN) frequency in peripheral T lymphocytes of twenty-three atomic bomb survivors with MDS and five normal individuals. The spontaneous- and X-ray-induced-MN frequencies were significantly higher in MDS patients than in normal individuals. Interestingly, radiation sensitivity increased along with the severity of MDS clinical subtypes. Because many of the patients in this study had not been exposed to chemo- or radiation-therapy, their unusual radiosensitivities may be related to their chromosomal or genomic instability. To explain the cause of unusual radiosensitivity, we measured the expression levels of four nucleotide excision repair (NER) genes (ERCC1, ERCC3, ERCC5 and XPC) in peripheral blood mononuclear cells using a reverse transcripts-polymerase chain reaction (RT-PCR) method. The ERCC5 gene was expressed at reduced levels in only one of 10 patients with mild symptom. Reduction of NER genes was expressed in four of 11 patients with severe symptom. Immortalized lymphoid cell lines were established from B-lymphocytes infected with Epstein-Barr virus in vitro. The abrogation of radiation-induced-G2/M arrnst was observed in some of MDS-B lymphoid cell lines, but not in the normal B lymphoid cell lines. Our data suggest that the control of chromosomal stability is impaired in pluripotent stem cells of MDS patients, and that DNA repair defects and loss of G2/M arrest may be involved in the pathophysiology of disease progression. (authors)

  20. Impact of baseline cytogenetic findings and cytogenetic response on outcome of high-risk myelodysplastic syndromes and low blast count AML treated with azacitidine. (United States)

    Sébert, Marie; Komrokji, Rami S; Sekeres, Mikkael A; Prebet, Thomas; Cluzeau, Thomas; Santini, Valeria; Gyan, Emmanuel; Sanna, Alessandro; Ali, Najla HAl; Hobson, Sean; Eclache, Virginie; List, Alan; Fenaux, Pierre; Adès, Lionel


    Karyotype according to the revised IPSS is a strong independent prognostic factor for overall survival (OS) in myelodysplastic syndromes (MDS), however established in untreated patients. The prognostic impact of cytogenetics and cytogenetic response (CyR) in MDS patients receiving azacitidine (AZA) remains uncertain. We examined the prognostic value of baseline cytogenetics and CyR for overall response rate (ORR) and OS in 702 AZA-treated higher risk MDS and low blast count acute myeloid leukemia (AML), including 493 (70%) with abnormal karyotype. None of the cytogenetic abnormalities had significant impact on ORR (43.9%) or complete response (15.35%), except 3q abnormalities and complex karyotypes, which were associated with a lower ORR. OS differed significantly across all R-IPSS cytogenetic subgroups (pcytogenetics. CyR was achieved in 32% of the 281 evaluable patients with abnormal cytogenetics, was complete (CCyR) in 71 (25.3%) patients. We found no correlation between hematological response and cytogenetic response and 21% of the patients with CCyR did not achieve morphological response. In the 281 patients, we found no impact of CyR on survival, but when restricting to MDS (ie: <20% marrow blasts) achievement of CCyR was associated with better OS. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. Decitabine improves progression-free survival in older high-risk MDS patients with multiple autosomal monosomies: results of a subgroup analysis of the randomized phase III study 06011 of the EORTC Leukemia Cooperative Group and German MDS Study Group. (United States)

    Lübbert, Michael; Suciu, Stefan; Hagemeijer, Anne; Rüter, Björn; Platzbecker, Uwe; Giagounidis, Aristoteles; Selleslag, Dominik; Labar, Boris; Germing, Ulrich; Salih, Helmut R; Muus, Petra; Pflüger, Karl-Heinz; Schaefer, Hans-Eckart; Bogatyreva, Lioudmila; Aul, Carlo; de Witte, Theo; Ganser, Arnold; Becker, Heiko; Huls, Gerwin; van der Helm, Lieke; Vellenga, Edo; Baron, Frédéric; Marie, Jean-Pierre; Wijermans, Pierre W


    In a study of elderly AML patients treated with the hypomethylating agent decitabine (DAC), we noted a surprisingly favorable outcome in the (usually very unfavorable) subgroup with two or more autosomal monosomies (MK2+) within a complex karyotype (Lübbert et al., Haematologica 97:393-401, 2012). We now analyzed 206 myelodysplastic syndrome (MDS) patients (88 % of 233 patients randomized in the EORTC/GMDSSG phase III trial 06011, 61 of them with RAEBt, i.e. AML by WHO) with cytogenetics informative for MK status.. Endpoints are the following: complete/partial (CR/PR) and overall response rate (ORR) and progression-free (PFS) and overall survival (OS). Cytogenetic subgroups are the following: 63 cytogenetically normal (CN) patients, 143 with cytogenetic abnormalities, 73 of them MK-negative (MK-), and 70 MK-positive (MK+). These MK+ patients could be divided into 17 with a single autosomal monosomy (MK1) and 53 with at least two monosomies (MK2+). ORR with DAC in CN patients: 36.1 %, in MK- patients: 16.7 %, in MK+ patients: 43.6 % (MK1: 44.4 %, MK2+ 43.3 %). PFS was prolonged by DAC compared to best supportive care (BSC) in the CN (hazard ratio (HR) 0.55, 99 % confidence interval (CI), 0.26; 1.15, p = 0.03) and MK2+ (HR 0.50; 99 % CI, 0.23; 1.06, p = 0.016) but not in the MK-, MK+, and MK1 subgroups. OS was not improved by DAC in any subgroup. In conclusion, we demonstrate for the first time in a randomized phase III trial that high-risk MDS patients with complex karyotypes harboring two or more autosomal monosomies attain encouraging responses and have improved PFS with DAC treatment compared to BSC.

  2. [Clinical Significance of ID4 Gene Mehtylation in Demethylation-Treated MDS Cell Line and 2 MDS Patients]. (United States)

    Kang, Hui-Yuan; Wang, Xin-Rong; Gao, Li; Wang, Wei; Li, Mian-Yang; Wang, Li-Li; Wang, Cheng-Bin; Yu, Li


    To evaluate significance of ID4 gene mehtylation in demethylating myelodysplastic syndrome(MDS) cell Line MUTZ1 and 2 patients with MDS. The methylation-specific PCR (MS-PCR) and reverse transcription-PCR (RT-PCR) were applied to identify the methylation status and gene expression of ID4 gene in MDS cell line MUTZ1, a patient with aplastic anemia(AA) and a donor with normal bone marrow (NBM). RT-PCR was applied to detect the ID4 gene expression status in MUTZ1 cell line treated with decitabine at 3 different concentrations. Then bisulfite sequencing PCR (BSP) was applied to detect ID4 gene methylation status in 2 MDS parients treated with decitabine. The MDS cell line MUTZ-1 displayed a complete methylation of ID4 gene promoter with little mRNA expression. Inversely, bone marrow of an AA patient and NBM showed complete unmethylation of this gene with intensity mRNA expression. With the increase of decitabine concentration, ID4 gene mRNA expression was more and more increased. After decitabine treatment, ID4 gene methylation-positive frequencies of both the 2 MDS patients were much more decreased than that of the first treatment. So, ID4 gene mRNA expression inhibited by promoter hypemethylation could be recovered by using demethylation medicine. ID4 as a new potential anti-oncogene suggests that its methylation may become a marker for selection and assessment of therapeutic schedules in patients with MDS.

  3. Myelodysplastic Syndrome, Unclassifiable (MDS-U) With 1% Blasts Is a Distinct Subgroup of MDS-U With a Poor Prognosis. (United States)

    Margolskee, Elizabeth; Hasserjian, Robert P; Hassane, Duane; Tam, Wayne; Mathew, Susan; Ok, Chi Young; Wang, Sa A; Oak, Jean; Arber, Daniel A; Orazi, Attilio


    Three situations qualify as myelodysplastic syndrome, unclassifiable (MDS-U): (1) refractory cytopenia with dysplasia and 1% blasts in peripheral blood (BL), (2) pancytopenia with unilineage dysplasia (Pan), and (3) persistent cytopenia, less than 5% bone marrow blasts, and less than 10% dysplastic cells and presence of MDS-defining cytogenetic abnormalities (CG). We compared the clinicopathologic features and mutational profiles for these three groups. MDS-U cases were reviewed at four major academic institutions. Targeted next-generation sequencing for genes implicated in myeloid neoplasms was performed in a subset of cases. Twenty-seven patients were identified (six MDS-U BL, 13 MDS-U Pan, and eight MDS-U CG). Clonal cytogenetic abnormalities were found in six of six, seven of 13, and eight of eight cases in MDS-U BL, Pan, and CG, respectively (P > .05). Overall, four of six patients with MDS-U BL progressed to acute myeloid leukemia; no MDS-U Pan or CG patients did. The rates of progression-free survival and mortality (overall survival) were significantly higher in MDS-U BL compared with Pan and CG (P MDS-U BL is a distinct subset of MDS-U with a poor prognosis, while MDS-U Pan and CG are relatively indolent. Evaluation of peripheral blood smears in patients with MDS is essential for accurate classification and prognosis. © American Society for Clinical Pathology, 2017. All rights reserved. For permissions, please e-mail:

  4. MDS system increases drilling safety and efficiency

    Energy Technology Data Exchange (ETDEWEB)

    Chevallier, J.; Turner, L. (Sedco Forex, Paris (FR))


    There's a great deal of data recorded during drilling operations on rigs these days, but it is seldom well utilized. The operator's company person relies upon mud loggers for collecting and recording most information. The methods used to process and display this information are often inadequate for those who need it the most the driller and toolpusher. Drilling contractor personnel usually have only rudimentary displays of drilling parameters, and practically no serious method of analysis except for daily paper reports. These are cumbersome to use and provide only incomplete data, after the fact. The MDS system, presented in this article, is a new information and alarm network, which rectifies this situation by bringing to the rig, for the first time, the latest in sensor and computer technologies. This system acquires key drilling data on the rig floor, pump room, and return line, and displays it in a clear graphical format to both the driller and the toolpusher in real time. It also provides the toolpusher with a workstation for easy access to the same information for evaluation and planning of the drilling program.

  5. Osteoblasts Protect AML Cells from SDF-1-Induced Apoptosis (United States)

    Kremer, Kimberly N.; Dudakovic, Amel; McGee-Lawrence, Meghan E.; Philips, Rachael L.; Hess, Allan D.; Smith, B. Douglas; van Wijnen, Andre J.; Karp, Judith E.; Kaufmann, Scott H.; Westendorf, Jennifer J.; Hedin, Karen E.


    The bone marrow provides a protective environment for acute myeloid leukemia (AML) cells that often allows leukemic stem cells to survive standard chemotherapeutic regimens. Targeting these leukemic stem cells within the bone marrow is critical for preventing relapse. We recently demonstrated that SDF-1, a chemokine abundant in the bone marrow, induces apoptosis in AML cell lines and in patient samples expressing high levels of its receptor, CXCR4. Here we show that a subset of osteoblast lineage cells within the bone marrow can protect AML cells from undergoing apoptosis in response to the SDF-1 naturally present in that location. In co-culture systems, osteoblasts at various stages of differentiation protected AML cell lines and patient isolates from SDF-1-induced apoptosis. The differentiation of the osteoblast cell lines, MC3T3 and W-20-17, mediated this protection via a cell contact-independent mechanism. In contrast, bone marrow-derived mesenchymal cells, the precursors of osteoblasts, induced apoptosis in AML cells via a CXCR4-dependent mechanism and failed to protect AML cells from exogenously added SDF-1. These results indicate that osteoblasts in the process of differentiation potently inhibit the SDF-1-driven apoptotic pathway of CXCR4-expressing AML cells residing in the bone marrow. Drugs targeting this protective mechanism could potentially provide a new approach to treating AML by enhancing the SDF-1-induced apoptosis of AML cells residing within the bone marrow microenvironment. PMID:24851270

  6. Resident Assessment Instrument/Minimum Data Set (RAI/MDS) (United States)

    Department of Veterans Affairs — The Resident Assessment Instrument/Minimum Data Set (RAI/MDS) is a comprehensive assessment and care planning process used by the nursing home industry since 1990 as...

  7. MDS 2.0 Public Quality Indicator and Resident Reports (United States)

    U.S. Department of Health & Human Services — The Minimum Data Set (MDS) is part of the federally mandated process for clinical assessment of all residents in Medicare or Medicaid certified nursing homes. This...

  8. Impact of chromosome alterations, genetic mutations and clonal hematopoiesis of indeterminate potential (CHIP) on the classification and risk stratification of MDS. (United States)

    Ganguly, Bani Bandana; Banerjee, Debasis; Agarwal, Mohan B


    The advent of technological development has undoubtedly advanced biological and molecular inputs for better understanding the heterogeneous hematopoietic pre-malignant disorder of the stem cells known as myelodysplastic syndromes (MDS). Chromosomal rearrangements, including del(3q/5q/7q/11q/12p/20q), loss of 5/7/Y, trisomy 8/19, i(17q), etc. frequently detected in MDS with variable frequencies and combinations, are the integral components of the 5-tier risk-stratification and WHO-2016 classification. Observations on mutations in genes involved in RNA-splicing, DNA methylation, chromatin modification, transcription factor, signal transduction/kinases, RAS pathway, cohesin complex, DNA repair and other pathways have given insights in independent effects and biological interaction of co-occurrence on disease-phenotype and treatment outcome. However, recent concepts of clonal hematopoiesis of indeterminate potential (CHIP) and idiopathic cytopenia of undetermined significance (ICUS) have urged a re-definition of mutational events in non-clonal cytopenia and non-MDS healthy elderly but with a higher risk of overt leukemia. Considering gene mutations, chromosomal alterations, CHIP, ICUS and their significance in classification and risk-scoring certainly presents a comprehensive picture of disease-phenotype towards better understanding of MDS-pathogenesis, its evolution to AML and its response to therapeutic agents. The present review summarizes chromosomal and gene mutations, co-existence of mutational complexity, and WHO-2016 classification and risk-stratifications of MDS to facilitate a better understanding of its pathogenesis. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. An improved resource management model based on MDS (United States)

    Yuan, Man; Sun, Changying; Li, Pengfei; Sun, Yongdong; He, Rui


    GRID technology provides a kind of convenient method for managing GRID resources. This service is so-called monitoring, discovering service. This method is proposed by Globus Alliance, in this GRID environment, all kinds of resources, such as computational resources, storage resources and other resources can be organized by MDS specifications. However, this MDS is a theory framework, particularly, in a small world intranet, in the case of limit of resources, the MDS has its own limitation. Based on MDS, an improved light method for managing corporation computational resources and storage resources is proposed in intranet(IMDS). Firstly, in MDS, all kinds of resource description information is stored in LDAP, it is well known although LDAP is a light directory access protocol, in practice, programmers rarely master how to access and store resource information into LDAP store, in such way, it limits MDS to be used. So, in intranet, these resources' description information can be stored in RDBMS, programmers and users can access this information by standard SQL. Secondly, in MDS, how to monitor all kinds of resources in GRID is not transparent for programmers and users. In such way, it limits its application scope, in general, resource monitoring method base on SNMP is widely employed in intranet, therefore, a kind of resource monitoring method based on SNMP is integrated into MDS. Finally, all kinds of resources in the intranet can be described by XML, and all kinds of resources' description information is stored in RDBMS, such as MySql, and retrieved by standard SQL, dynamic information for all kinds of resources can be sent to resource storage by SNMP, A prototype resource description, monitoring is designed and implemented in intranet.

  10. Modeling Marrow Failure and MDS for Novel Therapeutics (United States)


    syndrome (MDS) and leukemia is also markedly elevated in patients with inherited marrow failure syndromes compared to age-matched controls. Prognosis of...Novel Therapeutics W81XWH-16-1-0054 1. Introduction Clonal evolution is a potentially life threatening long-term complication of inherited and...The risk of early progression to myelodysplastic syndrome (MDS) and leukemia is also markedly elevated in patients with inherited marrow failure

  11. Myelodysplastic Syndromes (MDS) and autoimmune disorders (AD): cause or consequence? (United States)

    Braun, Thorsten; Fenaux, Pierre


    Myelodysplastic Syndromes (MDS) and Chronic Myelomonocytic Leukemia (CMML) are frequently associated with clinical manifestations of autoimmune disorders (AD) and inflammatory response of the immune system. AD accompanying MDS and CMML include vasculitis, seronegative polyarthritis and neutrophilic dermatosis. Rare AD including relapsing polychondritis is strongly associated with MDS as in a high proportion of those patients MDS is diagnosed during disease course. Antinuclear antibodies (ANA) are frequently found among MDS patients without clinical manifestation of AD. In a subset of patients, MDS and resulting cytopenias appear to be the consequence of auto reactive immunologic activity and may respond to immunosuppressive treatment (IST). Increased release of inflammatory cytokines like tumor necrosis factor-(TNF)-α and interferon (IF)-γ triggers apoptosis of myeloid precursor cells leading to cytopenias. Impaired function of immune cells including cytotoxic, regulatory (Treg), helper (Th17) T cells and NK cells also appears to predict response to IST, outcome and occurrence of AD. Copyright © 2013 Elsevier Ltd. All rights reserved.

  12. Genamplifikation in humanen Zellen: Untersuchungen an einem Leukämiefall und an HeLa-Zellen


    Bruckert, Petra


    Die cytogenetische Manifestation von Genamplifikation in humanen Zellen wurde in einem Fall von akuter myeloischer Leukämie (AML) sowie an der humanen Cervixcarcinomzelllinie HeLa S3 untersucht. In dem AML-Fall ergab die Karyotypisierung der Leukämiezellen neben dem Verlust eines X-Chromosoms das Vorliegen einer extrachromosomalen Genamplifikation in Form von Double Minutes. Mit Hilfe der Comparativen Genomischen Hybridisierung (CGH) und der Fluoreszenz-in situ-Hybridisierung (FISH) wurde die...

  13. Nassi-Schneiderman Diagram in HTML Based on AML (United States)

    Menyhárt, László


    In an earlier work I defined an extension of XML called Algorithm Markup Language (AML) for easy and understandable coding in an IDE which supports XML editing (e.g. NetBeans). The AML extension contains annotations and native language (English or Hungarian) tag names used when coding our algorithm. This paper presents a drawing tool with which…

  14. Cytomorphology review of 100 newly diagnosed lower-risk MDS patients in the European LeukemiaNet MDS (EUMDS) registry reveals a high inter-observer concordance

    NARCIS (Netherlands)

    Swart, L. de; Smith, A.; MacKenzie, M.; Symeonidis, A.; Neukirchen, J.; Mikulenkova, D.; Vallespi, T.; Zini, G.; Paszkowska-Kowalewska, M.; Kruger, A.; Saft, L.; Fenaux, P.; Bowen, D.; Hellstrom-Lindberg, E.; Cermak, J.; Stauder, R.; Tatic, A.; Holm, M.S.; Malcovati, L.; Madry, K.; Droste, J.A.; Blijlevens, N.M.; Witte, T.J. de; Germing, U.


    The European LeukemiaNet MDS (EUMDS) registry is collecting data of myelodysplastic syndrome (MDS) patients belonging to the IPSS low or intermediate-1 category, newly diagnosed by local cytologists. The diagnosis of MDS can be challenging, and some data report inter-observer variability with regard

  15. Monitoring the grid with the Globus Toolkit MDS4

    International Nuclear Information System (INIS)

    Schopf, Jennifer M; Pearlman, Laura; Miller, Neill; Kesselman, Carl; Foster, Ian; D'Arcy, Mike; Chervenak, Ann


    The Globus Toolkit Monitoring and Discovery System (MDS4) defines and implements mechanisms for service and resource discovery and monitoring in distributed environments. MDS4 is distinguished from previous similar systems by its extensive use of interfaces and behaviors defined in the WS-Resource Framework and WS-Notification specifications, and by its deep integration into essentially every component of the Globus Toolkit. We describe the MDS4 architecture and the Web service interfaces and behaviors that allow users to discover resources and services, monitor resource and service states, receive updates on current status, and visualize monitoring results. We present two current deployments to provide insights into the functionality that can be achieved via the use of these mechanisms

  16. The applicability of the WHO classification in paediatric AML. A NOPHO-AML study

    DEFF Research Database (Denmark)

    Sandahl, Julie D; Kjeldsen, Eigil; Abrahamsson, Jonas


    The World Health Organization (WHO) classification of myeloid leukaemia was revised in 2008. It incorporates newly recognized entities and emphasizes the pivotal role of cytogenetic abnormalities. The aim of this study was to evaluate the usability of the WHO classification when applied to a large......(7q) into one group. We found that -7 (n = 14) had significantly poorer outcome than del(7q) (n = 11); 5-year event-free survival 26% vs. 67%, (P = 0·02), and 5-year overall survival 51% vs. 90%, (P = 0·04). The largest group was the highly heterogeneous AML not otherwise specified (NOS) (n = 280...

  17. CNS Involvement in AML Patient Treated with 5-Azacytidine

    Directory of Open Access Journals (Sweden)

    Diamantina Vasilatou


    Full Text Available Central nervous system (CNS involvement in acute myeloid leukemia (AML is a rare complication of the disease and is associated with poor prognosis. Sometimes the clinical presentation can be unspecific and the diagnosis can be very challenging. Here we report a case of CNS infiltration in a patient suffering from AML who presented with normal complete blood count and altered mental status.

  18. Trisomy 8 in Pediatric Acute Myeloid Leukemia. A NOPHO-AML Study

    DEFF Research Database (Denmark)

    Laursen, Anne Cathrine Lund; Sandahl, Julie Damgaard; Kjeldsen, Eigil


    Trisomy 8 (+8) is a common cytogenetic aberration in acute myeloid leukemia (AML); however, the impact of +8 in pediatric AML is largely unknown. We retrospectively investigated 609 patients from the NOPHO-AML database to determine the clinical and cytogenetic characteristics of +8 in pediatric AML...

  19. Sport und soziale Integration


    Turan, Günes


    Sport und soziale Integration : Chancen, Probleme und Perspektiven für Städte und Kommunen ; Tagungsband der gleichnamigen Tagung am 28. und 29. Juni 2011 in Augsburg / Helmut Altenberger ... (Hrsg.). - Hamburg : Feldhaus, Ed. Czwalina, 2012. - 104 S. - (Sportwissenschaft und Sportpraxis ; 161)

  20. The MDS challenging behavior profile for long-term care

    NARCIS (Netherlands)

    Gerritsen, D. L.; Achterberg, W. P.; Steverink, N.; Frijters, D. H. M.; Ribbe, M. W.


    The objective was to construct a reliable and valid challenging behavior scale with items from the Minimum Data Set (MDS). Exploratory factor analyses of a sample of 656 nursing home residents yielded a 16-item Behavior Profile containing four internally consistent and valid subscales measuring

  1. Interaction mediated by the putative tip regions of MdsA and MdsC in the formation of a Salmonella-specific tripartite efflux pump.

    Directory of Open Access Journals (Sweden)

    Saemee Song

    Full Text Available To survive in the presence of a wide range of toxic compounds, gram-negative bacteria expel such compounds via tripartite efflux pumps that span both the inner and outer membranes. The Salmonella-specific MdsAB pump consists of MdsB, a resistance-nodulation-division (RND-type inner membrane transporter (IMT that requires the membrane fusion protein (MFP MdsA, and an outer membrane protein (OMP; MdsC or TolC to form a tripartite efflux complex. In this study, we investigated the role of the putative tip regions of MdsA and its OMPs, MdsC and TolC, in the formation of a functional MdsAB-mediated efflux pump. Comparative analysis indicated that although sequence homologies of MdsA and MdsC with other MFPs and OMPs, respectively, are extremely low, key residues in the putative tip regions of these proteins are well conserved. Mutagenesis studies on these conserved sites demonstrated their importance for the physical and functional interactions required to form an MdsAB-mediated pump. Our studies suggest that, despite differences in the primary amino acid sequences and functions of various OMPs and MFPs, interactions mediated by the conserved tip regions of OMP and MFP are required for the formation of functional tripartite efflux pumps in gram-negative bacteria.

  2. Handling missing values in the MDS-UPDRS. (United States)

    Goetz, Christopher G; Luo, Sheng; Wang, Lu; Tilley, Barbara C; LaPelle, Nancy R; Stebbins, Glenn T


    This study was undertaken to define the number of missing values permissible to render valid total scores for each Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) part. To handle missing values, imputation strategies serve as guidelines to reject an incomplete rating or create a surrogate score. We tested a rigorous, scale-specific, data-based approach to handling missing values for the MDS-UPDRS. From two large MDS-UPDRS datasets, we sequentially deleted item scores, either consistently (same items) or randomly (different items) across all subjects. Lin's Concordance Correlation Coefficient (CCC) compared scores calculated without missing values with prorated scores based on sequentially increasing missing values. The maximal number of missing values retaining a CCC greater than 0.95 determined the threshold for rendering a valid prorated score. A second confirmatory sample was selected from the MDS-UPDRS international translation program. To provide valid part scores applicable across all Hoehn and Yahr (H&Y) stages when the same items are consistently missing, one missing item from Part I, one from Part II, three from Part III, but none from Part IV can be allowed. To provide valid part scores applicable across all H&Y stages when random item entries are missing, one missing item from Part I, two from Part II, seven from Part III, but none from Part IV can be allowed. All cutoff values were confirmed in the validation sample. These analyses are useful for constructing valid surrogate part scores for MDS-UPDRS when missing items fall within the identified threshold and give scientific justification for rejecting partially completed ratings that fall below the threshold. © 2015 International Parkinson and Movement Disorder Society.

  3. Despite differential gene expression profiles pediatric MDS derived mesenchymal stromal cells display functionality in vitro. (United States)

    Calkoen, F G J; Vervat, C; van Pel, M; de Haas, V; Vijfhuizen, L S; Eising, E; Kroes, W G M; 't Hoen, P A C; van den Heuvel-Eibrink, M M; Egeler, R M; van Tol, M J D; Ball, L M


    Pediatric myelodysplastic syndrome (MDS) is a heterogeneous disease covering a spectrum ranging from aplasia (RCC) to myeloproliferation (RAEB(t)). In adult-type MDS there is increasing evidence for abnormal function of the bone-marrow microenvironment. Here, we extensively studied the mesenchymal stromal cells (MSCs) derived from children with MDS. MSCs were expanded from the bone-marrow of 17 MDS patients (RCC: n=10 and advanced MDS: n=7) and pediatric controls (n=10). No differences were observed with respect to phenotype, differentiation capacity, immunomodulatory capacity or hematopoietic support. mRNA expression analysis by Deep-SAGE revealed increased IL-6 expression in RCC- and RAEB(t)-MDS. RCC-MDS MSC expressed increased levels of DKK3, a protein associated with decreased apoptosis. RAEB(t)-MDS revealed increased CRLF1 and decreased DAPK1 expressions. This pattern has been associated with transformation in hematopoietic malignancies. Genes reported to be differentially expressed in adult MDS-MSC did not differ between MSC of pediatric MDS and controls. An altered mRNA expression profile, associated with cell survival and malignant transformation, of MSC derived from children with MDS strengthens the hypothesis that the micro-environment is of importance in this disease. Our data support the understanding that pediatric and adult MDS are two different diseases. Further evaluation of the pathways involved might reveal additional therapy targets. Copyright © 2015. Published by Elsevier B.V.

  4. 75 FR 16512 - Willstaff Staffing Agency, Willstaff Crystal, Inc., and MDS Industrial Resources, Inc., Working... (United States)


    ... Agency, Willstaff Crystal, Inc., and MDS Industrial Resources, Inc., Working On-Site at Tyler Pipe... MDS Industrial Resources, Inc., working on-site at Tyler Pipe Company, Waterworks Division, South... Staffing Agency, Willstaff Crystal, Inc., and MDS Industrial Resources, Inc., working on-site at Tyler Pipe...

  5. Some Families of Asymmetric Quantum MDS Codes Constructed from Constacyclic Codes (United States)

    Huang, Yuanyuan; Chen, Jianzhang; Feng, Chunhui; Chen, Riqing


    Quantum maximal-distance-separable (MDS) codes that satisfy quantum Singleton bound with different lengths have been constructed by some researchers. In this paper, seven families of asymmetric quantum MDS codes are constructed by using constacyclic codes. We weaken the case of Hermitian-dual containing codes that can be applied to construct asymmetric quantum MDS codes with parameters [[n,k,dz/dx

  6. The Hematopoietic Transcription Factors RUNX1 and ERG Prevent AML1-ETO Oncogene Overexpression and Onset of the Apoptosis Program in t(8;21) AMLs

    NARCIS (Netherlands)

    Mandoli, Amit; Singh, Abhishek A.; Prange, Koen H. M.; Tijchon, Esther; Oerlemans, Marjolein; Dirks, Rene; Ter Huurne, Menno; Wierenga, Albertus T. J.; Janssen-Megens, Eva M.; Berentsen, Kim; Sharifi, Nilofar; Kim, Bowon; Matarese, Filomena; Nguyen, Luan N.; Hubner, Nina C.; Rao, Nagesha A.; van den Akker, Emile; Altucci, Lucia; Vellenga, Edo; Stunnenberg, Hendrik G.; Martens, Joost H. A.


    The t(8;21) acute myeloid leukemia (AML)-associated oncoprotein AML1-ETO disrupts normal hematopoietic differentiation. Here, we have investigated its effects on the transcriptome and epigenome in t(8,21) patient cells. AML1-ETO binding was found at promoter regions of active genes with high levels

  7. New Insights into the Pathogenesis of MDS and the rational therapeutic opportunities. (United States)

    Abou Zahr, Abdallah; Bernabe Ramirez, Carolina; Wozney, Jocelyn; Prebet, Thomas; Zeidan, Amer M


    Myelodysplastic syndromes (MDS) include a heterogeneous group of acquired hematopoietic malignancies characterized by ineffective hematopoiesis, peripheral cytopenias, and a varying propensity for progression to acute myeloid leukemia. The clinical heterogeneity in MDS is a reflection of its molecular heterogeneity. Better understanding of aberrant epigenetics, dysregulation of immune responses, and del(5q) MDS has provided the rationale for well-established treatments in MDS. Further understanding of abnormal signal transduction and aberrant apoptosis pathways has led to development of new rational therapies that are in advanced phases of clinical translation. This review seeks to describe recent developments in our understanding of the pathogenesis of MDS and the potential therapeutic implications of these observations.

  8. Entanglement-assisted quantum MDS codes from negacyclic codes (United States)

    Lu, Liangdong; Li, Ruihu; Guo, Luobin; Ma, Yuena; Liu, Yang


    The entanglement-assisted formalism generalizes the standard stabilizer formalism, which can transform arbitrary classical linear codes into entanglement-assisted quantum error-correcting codes (EAQECCs) by using pre-shared entanglement between the sender and the receiver. In this work, we construct six classes of q-ary entanglement-assisted quantum MDS (EAQMDS) codes based on classical negacyclic MDS codes by exploiting two or more pre-shared maximally entangled states. We show that two of these six classes q-ary EAQMDS have minimum distance more larger than q+1. Most of these q-ary EAQMDS codes are new in the sense that their parameters are not covered by the codes available in the literature.

  9. The need for additional genetic markers for MDS stratification: what does the future hold for prognostication? (United States)

    Otrock, Zaher K.; Tiu, Ramon V.; Maciejewski, Jaroslaw P.; Sekeres, Mikkael A.


    Myelodysplastic syndromes (MDS) constitute a heterogeneous group of clonal hematopoietic disorders. Metaphase cytogenetics (MC) has been the gold standard for genetic testing in MDS, but it can detect clonal cytogenetic abnormalities in only 50% of cases. New karyotyping tests include fluorescence in situ hybridization (FISH), array-based comparative genomic hybridization (aCGH), and single nucleotide polymorphism arrays (SNP-A). These techniques have increased the detected genetic abnormalities in MDS, many of which confer prognostic significance to overall and leukemia-free survival. This has eventually increased our understanding of MDS genetics. With the help of new technologies, we anticipate that the existing prognostic scoring systems will incorporate mutational data into their parameters. This review discusses the progress in MDS diagnosis through the use of array-based technologies. We also discuss the recently investigated genetic mutation in MDS, and revisit the MDS classification and prognostic scoring systems. PMID:23373781

  10. To chelate or not to chelate in MDS: That is the question! (United States)

    Zeidan, Amer M; Griffiths, Elizabeth A


    Myelodysplastic syndromes (MDS) are a heterogeneous group of hemopathies that exhibit physical manifestations with clinical consequences of bone marrow failure and inherent risk of progression to acute myeloid leukemia. Iron overload (IO) is common in MDS due to chronic transfusion support and disease-related alterations in iron metabolism. IO has been conclusively associated with inferior outcomes among MDS patients. Despite lack of randomized trials showing a survival impact of iron chelation therapy (ICT), ICT is recommended by experts and guidelines for select MDS patients with IO and is often used. The availability of effective oral ICT agents has reignited the controversy regarding ICT use in patients with MDS and IO. Here we summarize the studies evaluating the value of ICT in MDS and suggest a practical approach for use of these therapies. We also highlight controversies regarding use of ICT in MDS and discuss some ongoing efforts to answer these questions. Copyright © 2018 Elsevier Ltd. All rights reserved.

  11. Outcome of poor response Paediatric AML using early SCT

    DEFF Research Database (Denmark)

    Wareham, Neval E; Heilmann, Carsten; Abrahamsson, Jonas


    ) or > 5% blasts after AM (n = 14, refractory disease). Poor response patients received intensively timed induction and proceeded to SCT when a donor was available. RESULTS: Thirty-one of 267 evaluable patients (12%) had a poor response. SCT was performed in 25; using matched unrelated donors in 13......BACKGROUND: Children with poor response acute myeloid leukaemia (AML) generally have a very poor outcome. Allogeneic stem cell transplantation (SCT) is often recommended for these children but the benefit is unclear. The aim of this study was to investigate survival for poor response AML patients...... treated with SCT. MATERIAL AND METHODS: Treatment was given according to the NOPHO-AML 2004 protocol. All patients received AIET (Cytarabine, Idarubicin, Etoposide, Thioguanine) and AM (Cytarabine, Mitoxantrone) as induction. We included poor response defined as > 15% blasts on day 15 after AIET (n = 17...


    Directory of Open Access Journals (Sweden)

    Francesco D'Alò


    Full Text Available Acute myeloid leukemia (AML is a clonal disorder of the hematopoietic stem cell, typical of the elderly, with a median age of over 60 years at diagnosis. In AML, older age is one of the strongest independent adverse prognostic factor, associated with decreased complete response rate, worse disease-free and overall survival, with highest rates of treatment related mortality, resistant disease and relapse, compared to younger patients. While clinical risk factors do not significantly differ between older and younger patients, outcomes are compromised in elderly patients not only by increased comorbidities and susceptibility to toxicity from therapy, but it is now recognized that elderly AML represents a biologically distinct disease, that is itself more aggressive and less responsive to therapy. In elderly individuals prolonged exposure to environmental carcinogens may be the basis for the aggressive biology of the disease. This may also be the basis for similarities between elderly AML and therapy-related myeloid malignancies, mimicking toxic effects of previous cytotoxic treatments on hematopoietic stem cells. Age is itself a risk factor for t-MN, which are more frequent in elderly patients, where also a shorter latency between treatment of primary tumor and t-MN has been reported. Similarities between therapy-related malignancies and elderly AML include morphological aspects, as the presence of multilineage dysplasia preceding and/or concomitant to the development of leukemia, and adverse cytogenetics, including poor karyotype and chromosome 5 and/or 7 abnormalities. Looking at molecular prognosticators in elderly AML, similar to t-MN,  reduced frequency of favorable factors, as reduced number of NPM1 and CEBPA mutated cases has been observed, together with increased incidence of negative factors, as increased MDR1 expression, accelerated telomere shortening  and frequency of methylation changes. Given the unfavorable prognosis of elderly and

  13. Clinical Features and Outcomes of 666 Cases with Therapy-Related Myelodysplastic Syndrome (t-MDS). (United States)

    El-Fattah, Mohamed Abd


    Therapy-related myelodysplastic syndrome (t-MDS) is a serious complication of chemoradiotherapy for primary diseases. This cohort was aimed to determine the clinical features and outcomes of t-MDS in comparison with de novo MDS. I retrieved data of 666 cases with t-MDS, and 29,703 cases with de novo MDS diagnosed between 2001 and 2012 from the database of U.S. National Cancer Institute. Survival curves were estimated, and Cox proportional hazards model was constructed. Compared with patients with de novo MDS, patients with t-MDS tended to be young (median age; 65 vs. 76 years, p  MDS than de novo MDS (17.2 months and 22% vs. 31 months and 32%, respectively, p  MDS cases, with a median follow-up of 16 months (range 1-143 months), 521 cases (78.2%) had died. Of which, 78 (15%) cases had died from acute myeloid leukemia, and 66 (12.7%) cases had died from solid cancers. Of the total 66 cases died from solid cancers; 19 cases (28.8%) died from cancer of lung/bronchus, 11 cases (16.7%) breast cancers, and 10 cases (15.2%) ovarian cancer. In a multivariate analysis adjusted for clinical features, calendar period and radiotherapy, the hazard of mortality was significantly low in de novo MDS compared with t-MDS (hazard ratio 0.59; p  MDS is a distinct entity of MDS in terms of clinical characteristics and prognosis.

  14. Cellular origin of prognostic chromosomal aberrations in AML patients

    DEFF Research Database (Denmark)

    Mora-Jensen, H.; Jendholm, J.; Rapin, N.


    chromosomal structural rearrangements and single nucleotide variants (SNVs). Conventional AML diagnostics and recent seminal next-generation sequencing (NGS) studies have identified more than 200 recurrent genetic aberrations presenting in various combinations in individual patients. Significantly, many...... of these aberrations occur in normal hematopoietic stem and progenitor cells (HSCs/HPCs) before definitive leukemic transformation through additional acquisition of a few (that is, mostly 1 or 2) leukemia-promoting driver aberrations. NGS studies on sorted bone marrow (BM) populations of AML patients with a normal...

  15. Outcome of poor response paediatric AML using early SCT. (United States)

    Wareham, Neval E; Heilmann, Carsten; Abrahamsson, Jonas; Forestier, Erik; Gustafsson, Britt; Ha, Shau-Yin; Heldrup, Jesper; Jahnukainen, Kirsi; Jónsson, Ólafur G; Lausen, Birgitte; Palle, Josefine; Zeller, Bernward; Hasle, Henrik


    Children with poor response acute myeloid leukaemia (AML) generally have a very poor outcome. Allogeneic stem cell transplantation (SCT) is often recommended for these children but the benefit is unclear. The aim of this study was to investigate survival for poor response AML patients treated with SCT. Treatment was given according to the NOPHO-AML 2004 protocol. All patients received AIET (Cytarabine, Idarubicin, Etoposide, Thioguanine) and AM (Cytarabine, Mitoxantrone) as induction. We included poor response defined as > 15% blasts on day 15 after AIET (n = 17) or > 5% blasts after AM (n = 14, refractory disease). Poor response patients received intensively timed induction and proceeded to SCT when a donor was available. Thirty-one of 267 evaluable patients (12%) had a poor response. SCT was performed in 25; using matched unrelated donors in 13, matched sibling donors in 6, cord blood donor in 4, and haploidentical donor in two. The median follow-up for the 31 poor responding patients was 2.6 years (range 0.4 - 8.1 years) and 3-year probability of survival 70% (95% CI 59-77%). The poor responders in the NOPHO-AML 2004 protocol had a favourable prognosis treated with time-intensive induction followed by SCT. © 2012 John Wiley & Sons A/S.

  16. The Mice Drawer System Tissue Sharing Program (MDS-TSP) (United States)

    Biticchi, Roberta; Cancedda, Ranieri; Cilli, Michele; Cotronei, Vittorio; Costa, Delfina; Liu, Yi; Piccardi, Federica; Pignataro, Salvatore; Ruggiu, Alessandra; Tasso, Roberta; Tavella, Sara

    Several organs and apparatus are affected by weightless conditions and in particular by the weightless experienced during space flights. Therefore space missions are good opportunities to investigate in a whole organism the controlling cellular and molecular mechanisms. For this type of studies mice represent an excellent animal model for several reasons: reduced body size, relatively short time needed to reach adulthood, availability of strains with different genetic background and of different transgenic lines, etc. In line with the International Space Station (ISS) development, the Italian Space Agency (ASI) contracted Thales Alenia Space Italia, the largest Italian aerospace industry, to design and build a spaceflight payload for rodent research on ISS, the Mouse Drawer System (MDS -see abstract P. Cipparelli et al.). This payload meets NIH guideline for several physical parameters to maintain 6 animals in good health conditions in a space environment. Given the interest of our laboratory in the microgravity induced skeleton alterations, we focused our attention on transgenic mice over-expressing pleiotrophin (PTN) under the control of the human bone specific osteocalcin promoter. This protein is a heparin-binding cytokine with different functions. PTN is expressed by the cells in an early differentiation stage and is upregulated in tissue injury and wound repair. PTN is specifically involved in bone formation, neurite outgrowth and angiogenesis. As PTN-transgenic mice show an increased bone mass and mineralization, we decided to use this mouse model in the flight experiment and to study its potential role in counteracting bone loss in microgravity. Not all mouse strains are equally suitable for flight. After preliminary tests in the MDS breadboard at our animal facility on the behavior of different mouse strains, PTN-transgenic mice originally obtained in the BDF strain were backcrossed in the C57Bl/J10 strain before being used in this study. In order to

  17. Telomerase inhibition effectively targets mouse and human AML stem cells and delays relapse following chemotherapy

    DEFF Research Database (Denmark)

    Bruedigam, Claudia; Bagger, Frederik Otzen; Heidel, Florian H.


    (-/-) LSCs express a specific gene expression signature that can be identified in human AML patient cohorts and is positively correlated with patient survival following chemotherapy. In xenografts of primary human AML, genetic or pharmacological inhibition of telomerase targets LSCs, impairs leukemia...... progression, and delays relapse following chemotherapy. Altogether, these results establish telomerase inhibition as an effective strategy for eliminating AML LSCs....

  18. Cost of transfusion-dependent myelodysplastic syndrome (MDS) from a German payer?s perspective



    Abstract No curative treatment exists for patients with myelodysplastic syndrome (MDS) besides allogeneic stem cell transplantation. Hence, palliative treatment is provided for a life time accruing high health care cost. As no study in cost of MDS exists in Germany, the objective of this study was to assess and analyze costs of transfusion-dependent low/intermediate-1-risk MDS in Germany from a payers? perspective. From seven centers, 116 low/intermediate-1-risk transfusion-depende...

  19. Insufficient stromal support in MDS results from molecular and functional deficits of mesenchymal stromal cells. (United States)

    Geyh, S; Oz, S; Cadeddu, R-P; Fröbel, J; Brückner, B; Kündgen, A; Fenk, R; Bruns, I; Zilkens, C; Hermsen, D; Gattermann, N; Kobbe, G; Germing, U; Lyko, F; Haas, R; Schroeder, T


    Ineffective hematopoiesis is a major characteristic of myelodysplastic syndromes (MDS) causing relevant morbidity and mortality. Mesenchymal stromal cells (MSC) have been shown to physiologically support hematopoiesis, but their contribution to the pathogenesis of MDS remains elusive. We show that MSC from patients across all MDS subtypes (n=106) exhibit significantly reduced growth and proliferative capacities accompanied by premature replicative senescence. Osteogenic differentiation was significantly reduced in MDS-derived MSC, indicated by cytochemical stainings and reduced expressions of Osterix and Osteocalcin. This was associated with specific methylation patterns that clearly separated MDS-MSC from healthy controls and showed a strong enrichment for biological processes associated with cellular phenotypes and transcriptional regulation. Furthermore, in MDS-MSC, we detected altered expression of key molecules involved in the interaction with hematopoietic stem and progenitor cells (HSPC), in particular Osteopontin, Jagged1, Kit-ligand and Angiopoietin as well as several chemokines. Functionally, this translated into a significantly diminished ability of MDS-derived MSC to support CD34+ HSPC in long-term culture-initiating cell assays associated with a reduced cell cycle activity. Taken together, our comprehensive analysis shows that MSC from all MDS subtypes are structurally, epigenetically and functionally altered, which leads to impaired stromal support and seems to contribute to deficient hematopoiesis in MDS.

  20. Osteolytic bone lesions – A rare presentation of AML M6.

    Directory of Open Access Journals (Sweden)

    Geetha N.


    Full Text Available Acute myeloid leukemia (AML M6 is a rare form of AML  accounting  for < 5 % of all AML.  Extramedullary involvement  is very rarely seen in this entity.  Skeletal lesion has not been described in AML M6 before. We discuss the case of  a 17 year old boy with AML M6 who presented with  osteolytic lesion of right humerus.  He was treated with  induction and consolidation chemotherapy. The present case is the first report in literature of AML M6 presenting with skeletal lesions.

  1. Successful treatment of congenital acute myeloid leukemia (AML-M6) in a premature infant. (United States)

    van Dongen, Joyce C A; Dalinghaus, Michiel; Kroon, Andre A; de Vries, Andrica C H; van den Heuvel-Eibrink, Marry M


    Congenital acute myeloid leukemia (AML), and especially AML-M6 is a rare disease with a poor prognosis. Moreover, reports of treatment outcome of congenital AML-M6 in premature infants are not available. We report the first treated case of congenital AML-M6 in a premature girl, who received a full AML protocol. She presented with blueberry-muffin spots, anemia, high white blood cell count, and serious cardiopulmonary distress. Peripheral blood smears showed AML-M6 blasts. After treatment with a sequential low-dose cytarabine after birth and full-dose AML treatment according to the MRC-12 protocol at the age of 2 months, she now is in continuous complete remission for 4 years.

  2. Physical properties of Kentucky's AML landslides: Case studies analyzed

    International Nuclear Information System (INIS)

    Iannacchione, A.T.; Vallejo, L.E.


    Once an abandoned mined land (AML) landslide occurs and is identified as an emergency, engineers must rapidly implement a slope stabilization design. Correct slope remediation solutions are generally derived from well-executed geotechnical examinations. This paper summarizes a large body of geotechnical data compiled by the US office of Surface Mining Reclamation and Enforcement (OSM) from AML landslides in eastern Kentucky. Special attention is placed on the examination of subsurface failures, phreatic water levels, soil profiles, and soil composition information from numerous borehole exploration programs. Strength properties calculated from laboratory procedures and stability analysis techniques were also reviewed. Laboratory-determined soil shear strength values were found to be higher than those inferred from stability analysis. This suggests that postfailure determinations of the phreatic surface may be largely inappropriate when used in stability analysis or that laboratory-measured shear strengths are ineffective in replicating in situ colluvium/spoil slope properties

  3. Socioeconomic Status (SES) and Childhood Acute Myeloid Leukemia (AML) Mortality (United States)

    Knoble, Naomi B.; Alderfer, Melissa A.; Hossain, Md Jobayer


    Socioeconomic status (SES) is a complex construct of multiple indicators, known to impact cancer outcomes, but has not been adequately examined among pediatric AML patients. This study aimed to identify the patterns of co-occurrence of multiple community-level SES indicators and to explore associations between various patterns of these indicators and pediatric AML mortality risk. A nationally representative US sample of 3,651 pediatric AML patients, aged 0–19 years at diagnosis was drawn from 17 Surveillance, Epidemiology, and End Results (SEER) database registries created between 1973 and 2012. Factor analysis, cluster analysis, stratified univariable and multivariable Cox proportional hazards models were used. Four SES factors accounting for 87% of the variance in SES indicators were identified: F1) economic/educational disadvantage, less immigration; F2) immigration-related features (foreign-born, language-isolation, crowding), less mobility F3) housing instability; and, F4) absence of moving. F1 and F3 showed elevated risk of mortality, adjusted hazards ratios (aHR) (95% CI): 1.07(1.02–1.12) and 1.05(1.00–1.10), respectively. Seven SES-defined cluster groups were identified. Cluster 1: (low economic/educational disadvantage, few immigration-related features, and residential-stability) showed the minimum risk of mortality. Compared to Cluster 1, Cluster 3: (high economic/educational disadvantage, high-mobility) and Cluster 6: (moderately-high economic/educational disadvantages, housing-instability and immigration-related features) exhibited substantially greater risk of mortality, aHR(95% CI) = 1.19(1.0–1.4) and 1.23 (1.1–1.5), respectively. Factors of correlated SES-indicators and their pattern-based groups demonstrated differential risks in the pediatric AML mortality indicating the need of special public-health attention in areas with economic-educational disadvantages, housing-instability and immigration-related features. PMID:27543948

  4. Measuring depression in nursing home residents with the MDS and GDS: an observational psychometric study

    Directory of Open Access Journals (Sweden)

    Fries Brant E


    Full Text Available Abstract Background The objective of this study was to examine the Minimum Data Set (MDS and Geriatric Depression Scale (GDS as measures of depression among nursing home residents. Methods The data for this study were baseline, pre-intervention assessment data from a research study involving nine nursing homes and 704 residents in Massachusetts. Trained research nurses assessed residents using the MDS and the GDS 15-item version. Demographic, psychiatric, and cognitive data were obtained using the MDS. Level of depression was operationalized as: (1 a sum of the MDS Depression items; (2 the MDS Depression Rating Scale; (3 the 15-item GDS; and (4 the five-item GDS. We compared missing data, floor effects, means, internal consistency reliability, scale score correlation, and ability to identify residents with conspicuous depression (chart diagnosis or use of antidepressant across cognitive impairment strata. Results The GDS and MDS Depression scales were uncorrelated. Nevertheless, both MDS and GDS measures demonstrated adequate internal consistency reliability. The MDS suggested greater depression among those with cognitive impairment, whereas the GDS suggested a more severe depression among those with better cognitive functioning. The GDS was limited by missing data; the DRS by a larger floor effect. The DRS was more strongly correlated with conspicuous depression, but only among those with cognitive impairment. Conclusions The MDS Depression items and GDS identify different elements of depression. This may be due to differences in the manifest symptom content and/or the self-report nature of the GDS versus the observer-rated MDS. Our findings suggest that the GDS and the MDS are not interchangeable measures of depression.

  5. Measuring depression in nursing home residents with the MDS and GDS: an observational psychometric study (United States)

    Koehler, Melissa; Rabinowitz, Terry; Hirdes, John; Stones, Michael; Carpenter, G Iain; Fries, Brant E; Morris, John N; Jones, Richard N


    Background The objective of this study was to examine the Minimum Data Set (MDS) and Geriatric Depression Scale (GDS) as measures of depression among nursing home residents. Methods The data for this study were baseline, pre-intervention assessment data from a research study involving nine nursing homes and 704 residents in Massachusetts. Trained research nurses assessed residents using the MDS and the GDS 15-item version. Demographic, psychiatric, and cognitive data were obtained using the MDS. Level of depression was operationalized as: (1) a sum of the MDS Depression items; (2) the MDS Depression Rating Scale; (3) the 15-item GDS; and (4) the five-item GDS. We compared missing data, floor effects, means, internal consistency reliability, scale score correlation, and ability to identify residents with conspicuous depression (chart diagnosis or use of antidepressant) across cognitive impairment strata. Results The GDS and MDS Depression scales were uncorrelated. Nevertheless, both MDS and GDS measures demonstrated adequate internal consistency reliability. The MDS suggested greater depression among those with cognitive impairment, whereas the GDS suggested a more severe depression among those with better cognitive functioning. The GDS was limited by missing data; the DRS by a larger floor effect. The DRS was more strongly correlated with conspicuous depression, but only among those with cognitive impairment. Conclusions The MDS Depression items and GDS identify different elements of depression. This may be due to differences in the manifest symptom content and/or the self-report nature of the GDS versus the observer-rated MDS. Our findings suggest that the GDS and the MDS are not interchangeable measures of depression. PMID:15627403

  6. Differential response to hypomethylating agents based on sex: a report on behalf of the MDS Clinical Research Consortium (MDS CRC). (United States)

    DeZern, Amy E; Zeidan, Amer M; Barnard, John; Hand, Wesley; Al Ali, Najla; Brown, Francis; Zimmerman, Cassie; Roboz, Gail J; Garcia-Manero, Guillermo; Steensma, David P; Komrokji, Rami S; Sekeres, Mikkael A


    First-line therapy for higher-risk myelodysplastic syndromes (MDS) includes decitabine (DAC) or azacitidine (AZA). Variables have not identified differential response rates between these. We assessed the influence of patient sex on outcomes including overall survival (OS) in 642 patients with higher-risk MDS treated with AZA or DAC. DAC-treated patients (35% of females, 31% of males) had marginally better OS than AZA-treated patients (p = .043), (median OS of 18.7 months versus 16.4 months), but the difference varied strongly by sex. Female patients treated with DAC had a longer median OS (21.1 months, 95% CI: 16.0-28.0) than female patients treated with AZA (13.2 months, 95% CI: 11.0-15.9; p = .0014), while for males there was no significant difference between HMAs (median OS 18.3 months with DAC versus 17.9 months for AZA, p = .59). The biological reason for this variability is unclear, but may be a consequence of differences in cytidine deaminase activity between men and women.

  7. Digitalisierung und Selbstbestimmung

    Directory of Open Access Journals (Sweden)

    Bezemek, Christoph


    Full Text Available Der vorliegende Beitrag skizziert das Zusammenspiel von Digitalisierung und individueller Selbstbestimmung, stellt die Frage, welche Herausforderungen dieses Zusammenspiel birgt und diskutiert, wie ihnen begegnet werden kann.

  8. Emotion, Motivation und Volition


    Ulich, Dieter


    Emotion, Motivation und Volition / D. Ulich ; V. Brandstätter ; P. M. Gollwitzer. - In: Psychologie / hrsg. von Dietrich Dörner ... - 2., überarb. und erw. Aufl. - Stuttgart u.a. : Kohlhammer, 1996. - S. 115-135

  9. A randomized assessment of adding the kinase inhibitor lestaurtinib to first-line chemotherapy for FLT3-mutated AML

    DEFF Research Database (Denmark)

    Knapper, Steven; Russell, Nigel; Gilkes, Amanda


    The clinical benefit of adding FMS-like tyrosine kinase-3 (FLT3)-directed small molecule therapy to standard first-line treatment of acute myeloid leukemia (AML) has not yet been established. As part of the UK AML15 and AML17 trials, patients with previously untreated AML and confirmed FLT3-activ...

  10. Maintenance treatment with azacytidine for patients with high-risk myelodysplastic syndromes (MDS) or acute myeloid leukaemia following MDS in complete remission after induction chemotherapy

    DEFF Research Database (Denmark)

    Grövdal, Michael; Karimi, Mohsen; Khan, Rasheed


    This prospective Phase II study is the first to assess the feasibility and efficacy of maintenance 5-azacytidine for older patients with high-risk myelodysplastic syndrome (MDS), chronic myelomonocytic leukaemia and MDS-acute myeloid leukaemia syndromes in complete remission (CR) after induction ......-IV thrombocytopenia and neutropenia occurred after 9.5 and 30% of the cycles, respectively, while haemoglobin levels increased during treatment. 5-azacytidine treatment is safe, feasible and may be of benefit in a subset of patients....

  11. Informationskompetenz und Information Literacy


    Ingold, Marianne


    Informationskompetenz ist heute als Begriff , Konzept und praktisches Tätigkeitsfeld von Bibliotheken weltweit etabliert. Entstehung, Verbreitung und Entwicklung von „Informationskompetenz“ im deutschsprachigen Raum stehen in engem Zusammenhang mit dem in den USA und international seit den 1980er Jahren diskutierten und praktisch umgesetzten Konzept der „Information Literacy“. Auch wenn die beiden Begriffe in der Regel gleichbedeutend verwendet werden, zeigt ein Vergleich der vorwiegend aus e...

  12. Transcriptome Profiling of Pediatric Core Binding Factor AML.

    Directory of Open Access Journals (Sweden)

    Chih-Hao Hsu

    Full Text Available The t(8;21 and Inv(16 translocations disrupt the normal function of core binding factors alpha (CBFA and beta (CBFB, respectively. These translocations represent two of the most common genomic abnormalities in acute myeloid leukemia (AML patients, occurring in approximately 25% pediatric and 15% of adult with this malignancy. Both translocations are associated with favorable clinical outcomes after intensive chemotherapy, and given the perceived mechanistic similarities, patients with these translocations are frequently referred to as having CBF-AML. It remains uncertain as to whether, collectively, these translocations are mechanistically the same or impact different pathways in subtle ways that have both biological and clinical significance. Therefore, we used transcriptome sequencing (RNA-seq to investigate the similarities and differences in genes and pathways between these subtypes of pediatric AMLs. Diagnostic RNA from patients with t(8;21 (N = 17, Inv(16 (N = 14, and normal karyotype (NK, N = 33 were subjected to RNA-seq. Analyses compared the transcriptomes across these three cytogenetic subtypes, using the NK cohort as the control. A total of 1291 genes in t(8;21 and 474 genes in Inv(16 were differentially expressed relative to the NK controls, with 198 genes differentially expressed in both subtypes. The majority of these genes (175/198; binomial test p-value < 10(-30 are consistent in expression changes among the two subtypes suggesting the expression profiles are more similar between the CBF cohorts than in the NK cohort. Our analysis also revealed alternative splicing events (ASEs differentially expressed across subtypes, with 337 t(8;21-specific and 407 Inv(16-specific ASEs detected, the majority of which were acetylated proteins (p = 1.5 x 10(-51 and p = 1.8 x 10(-54 for the two subsets. In addition to known fusions, we identified and verified 16 de novo fusions in 43 patients, including three fusions involving NUP98 in six

  13. Despite differential gene expression profiles pediatric MDS derived mesenchymal stromal cells display functionality in vitro

    Directory of Open Access Journals (Sweden)

    F.G.J. Calkoen


    An altered mRNA expression profile, associated with cell survival and malignant transformation, of MSC derived from children with MDS strengthens the hypothesis that the micro-environment is of importance in this disease. Our data support the understanding that pediatric and adult MDS are two different diseases. Further evaluation of the pathways involved might reveal additional therapy targets.

  14. TOPICS-MDS: Veelzijdige bron voor wetenschappelijke en maatschappelijke kennisgeneratie ten behoeve van de ouderenzorg

    NARCIS (Netherlands)

    van den Brink, D.; Lutomski, J.E.; Qin, L.; den Elzen, W.P.J.; Kempen, G.I.J.M.; Krabbe, P.F.M.; Steyerberg, E.W.; Muntinga, M.E.; Moll van Charante, E.P.; Bleijenberg, N.; Olde Rikkert, M.G.M.; Melis, R.J.F.


    Developed as part of the National Care for the Elderly Programme (NPO), TOPICS-MDS is a uniform, national database on the health and wellbeing of the older persons and caregivers who participated in NPO-funded projects. TOPICS-MDS Consortium has gained extensive experience in constructing a

  15. Minimal clinically important difference on the Motor Examination part of MDS-UPDRS. (United States)

    Horváth, Krisztina; Aschermann, Zsuzsanna; Ács, Péter; Deli, Gabriella; Janszky, József; Komoly, Sámuel; Balázs, Éva; Takács, Katalin; Karádi, Kázmér; Kovács, Norbert


    Recent studies increasingly utilize the Movement Disorders Society Sponsored Unified Parkinson's Disease Rating Scale (MDS-UPDRS). However, the minimal clinically important difference (MCID) has not been fully established for MDS-UPDRS yet. To assess the MCID thresholds for MDS-UPDRS Motor Examination (Part III). 728 paired investigations of 260 patients were included. At each visit both MDS-UPDRS and Clinician-reported Global Impression-Improvement (CGI-I) scales were assessed. MDS-UPDRS Motor Examination (ME) score changes associated with CGI-I score 4 (no change) were compared with MDS-UPDRS ME score changes associated with CGI-I score 3 (minimal improvement) and CGI-I score 5 (minimal worsening). Both anchor- and distribution-based techniques were utilized to determine the magnitude of MCID. The MCID estimates for MDS-UPDRS ME were asymmetric: -3.25 points for detecting minimal, but clinically pertinent, improvement and 4.63 points for observing minimal, but clinically pertinent, worsening. MCID is the smallest change of scores that are clinically meaningful to patients. These MCID estimates may allow the judgement of a numeric change in MDS-UPDRS ME on its clinical importance. Copyright © 2015 Elsevier Ltd. All rights reserved.

  16. Apoptosis-Related Gene Expression Profiling in Hematopoietic Cell Fractions of MDS Patients

    NARCIS (Netherlands)

    MC Langemeijer, Saskia; Mariani, Niccolo; Knops, Ruth; Gilissen, Christian; Woestenenk, Rob; de Witte, Theo; Huls, Gerwin; van der Reijden, Bert A.; Jansen, Joop H.


    Although the vast majority of patients with a myelodysplastic syndrome (MDS) suffer from cytopenias, the bone marrow is usually normocellular or hypercellular. Apoptosis of hematopoietic cells in the bone marrow has been implicated in this phenomenon. However, in MDS it remains only partially

  17. New q-ary quantum MDS codes with distances bigger than q/2 (United States)

    He, Xianmang; Xu, Liqing; Chen, Hao


    The construction of quantum MDS codes has been studied by many authors. We refer to the table in page 1482 of (IEEE Trans Inf Theory 61(3):1474-1484, 2015) for known constructions. However, there have been constructed only a few q-ary quantum MDS [[n,n-2d+2,d

  18. Therapy with low-dose azacitidine for MDS in children and young adults: a retrospective analysis of the EWOG-MDS study group. (United States)

    Cseh, Annamaria M; Niemeyer, Charlotte M; Yoshimi, Ayami; Catala, Albert; Frühwald, Michael C; Hasle, Henrik; van den Heuvel-Eibrink, Mary M; Lauten, Melchior; De Moerloose, Barbara; Smith, Owen P; Bernig, Toralf; Gruhn, Bernd; Kulozik, Andreas E; Metzler, Markus; Olcay, Lale; Suttorp, Meinolf; Furlan, Ingrid; Strahm, Brigitte; Flotho, Christian


    Low-dose azacitidine is efficient and safe in the therapy of malignant myeloid disorders in adults but data in children are lacking. We present a retrospective analysis of 24 children and young adults with myelodysplastic syndrome (MDS) who received azacitidine at the time of first diagnosis or relapse after allotransplant (2 children were treated with azacitidine both initially and for relapse). Diagnoses were refractory cytopenia of childhood (N = 4), advanced primary MDS (N = 9) and secondary MDS (N = 11). The median duration of treatment was four cycles. Azacitidine was well tolerated, but cytopenias led to dose reduction in five cases. Treatment was discontinued in one child because of impaired renal function. Sixteen MDS patients were treated with azacitidine at first diagnosis. One complete clinical remission was observed and one child showed complete marrow remission; six children experienced stable disease with haematological improvement. Ten children received azacitidine for relapsed MDS after transplant: of these, seven experienced stable disease for 2-30 cycles (median 3), including one patient with haematological improvement for seven cycles. In summary, azacitidine is effective in some children with MDS and appears to be a non-toxic option in palliative situations to prolong survival. © 2016 John Wiley & Sons Ltd.


    Horvath, Krisztina; Aschermann Zsuzsanna; Acs, Péter; Bosnyák, Edit; Deli, Gabriella; Pál, Endre; Késmárki, Ildikó; Horváth Réka; Takács, Katalin; Komoly, Sámuel; Bokor, Magdolna; Rigó, Eszter; Lajtos, Júlia; Klivényi, Péter; Dibó, György; Vécsei, László; Takáts, Annamária; Tóth, Adrián; Imre, Piroska; Nagy, Ferenc; Herceg, Mihály; Hidasi, Eszter; Kovács, Norbert


    The Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) has been published in 2008 as the successor of the original UPDRS. The MDS-UPDRS organizing team developed guidelines for the development of official non-English translations consisting of four steps: translation/back-translation, cognitive pretesting, large field testing, and clinimetric analysis. The aim of this paper was to introduce the new MDS-UPDRS and its validation process into Hungarian. Two independent groups of neurologists translated the text of the MDS-UPDRS into Hungarian and subsequently back-translated into English. After the review of the back-translated English version by the MDS-UPDRS translation administration team, cognitive pretesting was conducted with ten patients. Based on the results of the initial cognitive pretesting, another round was conducted. For the large field testing phase, the Hungarian official working draft version of MDS-UPDRS was tested with 357 patients with Parkinson's disease (PD). Confirmatory factor analyses (CFA) determined whether the factor structure for the English-language MDS-UPDRS could be confirmed in data collected using the Hungarian Official Draft Version. To become an official translation, the Comparative Fit Index (CFI) had to be ≥ 0.90 compared to the English-language version. For all four parts of the Hungarian MDS-UPDRS, the CFI was ≥ 0.94. The overall factor structure of the Hungarian version was consistent with that of the English version based on the high CFIs for all the four parts of the MDS-UPDRS in the CFA; therefore, this version was designated as the "OFFICIAL GUNGARIAN VERSION OF THE MDS-UPDRS'.

  20. Romanistik und gender studies

    Directory of Open Access Journals (Sweden)

    Susanne Schlünder


    Full Text Available Die beiden Bände bieten ein breites Spektrum von Beiträgen zur französischen, italienischen und spanischen Literaturwissenschaft. Gedankliche Grundlage der im einzelnen unterschiedlichen Ansätze und Zielsetzungen ist ein im Anschluß an Judith Butler gender-reflektierendes, diskursives Konzept von Geschlecht, dessen wissenschaftsgeschichtliche Herleitung und Perspektiven Renate Kroll einleitend darlegt. Die einzelnen Artikel beschäftigen sich zum einen mit literarischen Strategien, die Schriftstellerinnen vom Mittelalter bis zur Gegenwart erprobt haben, und hinterfragen dabei die Rolle weiblicher Autoren in Literaturgeschichte und Literaturgeschichtsschreibung. Zum anderen widmen sie sich den literarischen Inszenierungs- und Repräsentationsformen von Weiblichkeit und stellen darüber einen Bezug zur Lebenswelt der behandelten Autorinnen her.

  1. The role of therapeutic leukapheresis in hyperleukocytotic AML.

    Directory of Open Access Journals (Sweden)

    Friederike Pastore

    Full Text Available Hyperleukocytosis in AML with leukostasis is a serious life-threatening condition leading to a high early mortality which requires immediate cytoreductive therapy. Therapeutic leukapheresis is currently recommended by the American Society of Apheresis in patients with a WBC>100 G/l with signs of leukostasis, but the role of prophylactic leukapheresis before clinical signs of leukostasis occur is unclear.We retrospectively analyzed the role of leukapheresis in 52 patients (median age 60 years with hyperleukocytotic AML with and without clinical signs of leukostasis. Since leukapheresis was performed more frequently in patients with signs of leukostasis due to the therapeutic policy in our hospital, we developed a risk score for early death within seven days after start of therapy (EDd7 to account for this selection bias and to independently measure the effect of leukapheresis on EDd7.20 patients received leukapheresis in combination to chemotherapy compared to 32 patients who received chemotherapy only. In a multivariate logistic regression model for the estimation of the probability of EDd7 thromboplastin time and creatinine remained as independent significant parameters and were combined to create an EDd7 risk score. The effect of leukapheresis on EDd7 was evaluated in a bivariate logistic regression together with the risk score. Leukapheresis did not significantly change early mortality in all patients with a WBC≥100 G/l.Prophylactic leukapheresis in hyperleukocytotic patients with and without leukostasis did not improve early mortality in our retrospective study. Larger and prospective clinical trials are needed to validate the risk score and to further explore the role of leukapheresis in AML with hyperleukocytosis.

  2. Epigenetically Aberrant Stroma in MDS Propagates Disease via Wnt/β-Catenin Activation. (United States)

    Bhagat, Tushar D; Chen, Si; Bartenstein, Matthias; Barlowe, A Trevor; Von Ahrens, Dagny; Choudhary, Gaurav S; Tivnan, Patrick; Amin, Elianna; Marcondes, A Mario; Sanders, Mathijs A; Hoogenboezem, Remco M; Kambhampati, Suman; Ramachandra, Nandini; Mantzaris, Iaonnis; Sukrithan, Vineeth; Laurence, Remi; Lopez, Robert; Bhagat, Prafullla; Giricz, Orsi; Sohal, Davendra; Wickrema, Amittha; Yeung, Cecilia; Gritsman, Kira; Aplan, Peter; Hochedlinger, Konrad; Yu, Yiting; Pradhan, Kith; Zhang, Jinghang; Greally, John M; Mukherjee, Siddhartha; Pellagatti, Andrea; Boultwood, Jacqueline; Will, Britta; Steidl, Ulrich; Raaijmakers, Marc H G P; Deeg, H Joachim; Kharas, Michael G; Verma, Amit


    The bone marrow microenvironment influences malignant hematopoiesis, but how it promotes leukemogenesis has not been elucidated. In addition, the role of the bone marrow stroma in regulating clinical responses to DNA methyltransferase inhibitors (DNMTi) is also poorly understood. In this study, we conducted a DNA methylome analysis of bone marrow-derived stromal cells from myelodysplastic syndrome (MDS) patients and observed widespread aberrant cytosine hypermethylation occurring preferentially outside CpG islands. Stroma derived from 5-azacytidine-treated patients lacked aberrant methylation and DNMTi treatment of primary MDS stroma enhanced its ability to support erythroid differentiation. An integrative expression analysis revealed that the WNT pathway antagonist FRZB was aberrantly hypermethylated and underexpressed in MDS stroma. This result was confirmed in an independent set of sorted, primary MDS-derived mesenchymal cells. We documented a WNT/β-catenin activation signature in CD34 + cells from advanced cases of MDS, where it associated with adverse prognosis. Constitutive activation of β-catenin in hematopoietic cells yielded lethal myeloid disease in a NUP98-HOXD13 mouse model of MDS, confirming its role in disease progression. Our results define novel epigenetic changes in the bone marrow microenvironment, which lead to β-catenin activation and disease progression of MDS. Cancer Res; 77(18); 4846-57. ©2017 AACR . ©2017 American Association for Cancer Research.

  3. MPL expression on AML blasts predicts peripheral blood neutropenia and thrombocytopenia. (United States)

    Rauch, Philipp J; Ellegast, Jana M; Widmer, Corinne C; Fritsch, Kristin; Goede, Jeroen S; Valk, Peter J M; Löwenberg, Bob; Takizawa, Hitoshi; Manz, Markus G


    Although the molecular pathways that cause acute myeloid leukemia (AML) are increasingly well understood, the pathogenesis of peripheral blood cytopenia, a major cause of AML mortality, remains obscure. A prevailing assumption states that AML spatially displaces nonleukemic hematopoiesis from the bone marrow. However, examining an initial cohort of 223 AML patients, we found no correlation between bone marrow blast content and cytopenia, questioning the displacement theory. Measuring serum concentration of thrombopoietin (TPO), a key regulator of hematopoietic stem cells and megakaryocytes, revealed loss of physiologic negative correlation with platelet count in AML cases with blasts expressing MPL, the thrombopoietin (scavenging) receptor. Mechanistic studies demonstrated that MPL hi blasts could indeed clear TPO, likely therefore leading to insufficient cytokine levels for nonleukemic hematopoiesis. Microarray analysis in an independent multicenter study cohort of 437 AML cases validated MPL expression as a central predictor of thrombocytopenia and neutropenia in AML. Moreover, t(8;21) AML cases demonstrated the highest average MPL expression and lowest average platelet and absolute neutrophil counts among subgroups. Our work thus explains the pathophysiology of peripheral blood cytopenia in a relevant number of AML cases. © 2016 by The American Society of Hematology.

  4. AML with t(7;12)(q36;p13) is associated with infancy and trisomy 19. Data from NOPHO-AML and review of the literature

    DEFF Research Database (Denmark)

    Espersen, Anne Dorte Lerche; Noren-Nyström, Ulrika; Abrahamsson, Jonas


    The t(7;12)(q36;p13) (MNX1/ETV6) is not included in the WHO classification but has been described in up to 30% of acute myeloid leukemia (AML) in children ...). A literature review identified 35 patients with this translocation, published between 2000 and 2015. Outcome data were available in 22 cases. The NOPHO-AML (Nordic Society for Pediatric Hematology and Oncology) database contained 651 patients with AML from 1993 to 2014 and seven (1.1%) had the translocation...

  5. Isoform-specific potentiation of stem and progenitor cell engraftment by AML1/RUNX1.

    Directory of Open Access Journals (Sweden)

    Shinobu Tsuzuki


    Full Text Available AML1/RUNX1 is the most frequently mutated gene in leukaemia and is central to the normal biology of hematopoietic stem and progenitor cells. However, the role of different AML1 isoforms within these primitive compartments is unclear. Here we investigate whether altering relative expression of AML1 isoforms impacts the balance between cell self-renewal and differentiation in vitro and in vivo.The human AML1a isoform encodes a truncated molecule with DNA-binding but no transactivation capacity. We used a retrovirus-based approach to transduce AML1a into primitive haematopoietic cells isolated from the mouse. We observed that enforced AML1a expression increased the competitive engraftment potential of murine long-term reconstituting stem cells with the proportion of AML1a-expressing cells increasing over time in both primary and secondary recipients. Furthermore, AML1a expression dramatically increased primitive and committed progenitor activity in engrafted animals as assessed by long-term culture, cobblestone formation, and colony assays. In contrast, expression of the full-length isoform AML1b abrogated engraftment potential. In vitro, AML1b promoted differentiation while AML1a promoted proliferation of progenitors capable of short-term lymphomyeloid engraftment. Consistent with these findings, the relative abundance of AML1a was highest in the primitive stem/progenitor compartment of human cord blood, and forced expression of AML1a in these cells enhanced maintenance of primitive potential both in vitro and in vivo.These data demonstrate that the "a" isoform of AML1 has the capacity to potentiate stem and progenitor cell engraftment, both of which are required for successful clinical transplantation. This activity is consistent with its expression pattern in both normal and leukaemic cells. Manipulating the balance of AML1 isoform expression may offer novel therapeutic strategies, exploitable in the contexts of leukaemia and also in cord blood

  6. Mammalian-target of rapamycin inhibition with temsirolimus in myelodysplastic syndromes (MDS) patients is associated with considerable toxicity: results of the temsirolimus pilot trial by the German MDS Study Group (D-MDS). (United States)

    Wermke, Martin; Schuster, Claudia; Nolte, Florian; Al-Ali, Haifa-Kathrin; Kiewe, Philipp; Schönefeldt, Claudia; Jakob, Christiane; von Bonin, Malte; Hentschel, Leopold; Klut, Ina-Maria; Ehninger, Gerhard; Bornhäuser, Martin; Baretton, Gustavo; Germing, Ulrich; Herbst, Regina; Haase, Detelef; Hofmann, Wolf K; Platzbecker, Uwe


    The mammalian-target of rapamycin (also termed mechanistic target of rapamycin, mTOR) pathway integrates various pro-proliferative and anti-apoptotic stimuli and is involved in regulatory T-cell (TREG) development. As these processes contribute to the pathogenesis of myelodysplastic syndromes (MDS), we hypothesized that mTOR modulation with temsirolimus (TEM) might show activity in MDS. This prospective multicentre trial enrolled lower and higher risk MDS patients, provided that they were transfusion-dependent/neutropenic or relapsed/refractory to 5-azacitidine, respectively. All patients received TEM at a weekly dose of 25 mg. Of the 9 lower- and 11 higher-risk patients included, only 4 (20%) reached the response assessment after 4 months of treatment and showed stable disease without haematological improvement. The remaining patients discontinued TEM prematurely due to adverse events. Median overall survival (OS) was not reached in the lower-risk group and 296 days in the higher-risk group. We observed a significant decline of bone marrow (BM) vascularisation (P = 0·006) but were unable to demonstrate a significant impact of TEM on the balance between TREG and pro-inflammatory T-helper-cell subsets within the peripheral blood or BM. We conclude that mTOR-modulation with TEM at a dose of 25 mg per week is accompanied by considerable toxicity and has no beneficial effects in elderly MDS patients. © 2016 John Wiley & Sons Ltd.

  7. Fotografie und atomare Katastrophe


    Bürkner, Daniel


    Die Dissertation setzt sich mit den fotografischen Repräsentationen der Atombombenabwürfe auf Hiroshima und Nagasaki sowie der Havarie des Kernkraftwerks Tschernobyl auseinander. Dabei werden künstlerische, dokumentarische und touristische Bilder analysiert, die sich der jeweiligen Strahlenkatastrophe oftmals erst Jahre nach dem Ereignis annehmen und ikonografische oder medial-materielle Bezüge zu ihr aufweisen. Es zeigen sich zentrale Strategien, atomare Katastrophen, seien sie militäri...

  8. MDS 3.0 for Nursing Homes and Swing Bed Providers (United States)

    U.S. Department of Health & Human Services — The MDS is a powerful tool for implementing standardized assessment and for facilitating care management in nursing homes (NHs) and non-critical access hospital...

  9. Versicherung und volkswirtschaftlicher Kreislauf


    Lampert, Heinz


    Versicherung und volkswirtschaftlicher Kreislauf : zur Behandlung d. Privatversicherung in d. volkswirtschaftl. Gesamtrechnung. - In: Zeitschrift für die gesamte Versicherungswissenschaft. 71. 1982. S. 189-210

  10. Minimum variance and variance of outgoing quality limit MDS-1(c1, c2) plans (United States)

    Raju, C.; Vidya, R.


    In this article, the outgoing quality (OQ) and total inspection (TI) of multiple deferred state sampling plans MDS-1(c1,c2) are studied. It is assumed that the inspection is rejection rectification. Procedures for designing MDS-1(c1,c2) sampling plans with minimum variance of OQ and TI are developed. A procedure for obtaining a plan for a designated upper limit for the variance of the OQ (VOQL) is outlined.

  11. Asymptotically Matched Layer (AML) for transient wave propagation in a moving frame of reference

    DEFF Research Database (Denmark)

    Madsen, Stine Skov; Krenk, Steen


    The paper presents an Asymptotically Matched Layer (AML) formulation in a moving frame of reference for transient dynamic response of a multi-layer 2D half-space. A displacement based finite element formulation of the convected domain problem is presented together with the AML formulation in whic...

  12. Initiation of MLL-rearranged AML is dependent on C/EBPα

    DEFF Research Database (Denmark)

    Ohlsson, Ewa; Hasemann, Marie Sigurd; Willer, Anton


    have compared gene expression profiles from human MLL-rearranged AML to normal progenitors and identified the myeloid tumor suppressor C/EBPα as a putative collaborator in MLL-rearranged AML. Interestingly, we find that deletion of Cebpa rendered murine hematopoietic progenitors completely resistant...

  13. Independent Validation of the SEND-PD and Correlation with the MDS-UPDRS Part IA

    Directory of Open Access Journals (Sweden)

    Mayela Rodríguez-Violante


    Full Text Available Introduction. Neuropsychiatric symptoms in Parkinson’s disease can be assessed by the MDS-UPDRS part IA. The Scale for Evaluation of Neuropsychiatric Disorders in Parkinson’s disease (SEND-PD has been recently developed to assess the severity of some neuropsychiatric symptoms. The objective of this study is to compare the performance of the SEND-PD with the corresponding items of the MDS-UPDRS part IA. Methods. Patients with Parkinson’s disease were evaluated using the MDS-UPDRS and the SEND-PD by independent raters. Partial SEND-PD and neuropsychiatric MDS-UPDRS part IA were constructed with equivalent items for comparison. Results. A total of 260 consecutive patients were included. Overall, 61.2% of the patients did not report any psychotic symptom and 83.5% did not report any ICD symptom. On the other hand, 78.5% of the patients did report at least one symptom related to apathy, depression, or anxiety. The partial SEND-PD score was 2.9±3.1 (range from 0 to 16. The neuropsychiatric MDS-UPDRS part IA score was 2.9±3 (range from 0 to 14. The correlation coefficient between corresponding items ranged from 0.67 to 0.98 and between both summary indexes was rs=0.93 (all, P<0.001. Conclusion. A high association between equivalent items of the SEND-PD and the MDS-UPDRS was found.

  14. Age-related inflammatory bone marrow microenvironment induces ineffective erythropoiesis mimicking del(5q) MDS. (United States)

    Mei, Y; Zhao, B; Basiorka, A A; Yang, J; Cao, L; Zhang, J; List, A; Ji, P


    Anemia is characteristic of myelodysplastic syndromes (MDS). The mechanisms of anemia in MDS are unclear. Using a mouse genetic approach, here we show that dual deficiency of mDia1 and miR-146a, encoded on chromosome 5q and commonly deleted in MDS (del(5q) MDS), causes an age-related anemia and ineffective erythropoiesis mimicking human MDS. We demonstrate that the ageing bone marrow microenvironment is important for the development of ineffective erythropoiesis in these mice. Damage-associated molecular pattern molecules (DAMPs), whose levels increase in ageing bone marrow, induced TNFα and IL-6 upregulation in myeloid-derived suppressor cells (MDSCs) in mDia1/miR-146a double knockout mice. Mechanistically, we reveal that pathologic levels of TNFα and IL-6 inhibit erythroid colony formation and differentially affect terminal erythropoiesis through reactive oxygen species-induced caspase-3 activation and apoptosis. Treatment of the mDia1/miR-146a double knockout mice with all-trans retinoic acid, which promoted the differentiation of MDSCs and ameliorated the inflammatory bone marrow microenvironment, significantly rescued anemia and ineffective erythropoiesis. Our study underscores the dual roles of the ageing microenvironment and genetic abnormalities in the pathogenesis of ineffective erythropoiesis in del(5q) MDS.

  15. [Initial subretinal localization of acute myeloblastic leukemia (AML5) recurrence]. (United States)

    Le Gall, S; François, S; Urier, N; Genevieve, F; d'Hermies, F; Rachieru, P; Ifrah, N


    Reduced visual acuity in patients with acute leucemia can result from many causes including an ocular localization. A patient previously treated for acute myeloblastic leucemia-5 (AML5) developed bilateral vision impairment related to a subretinal localization of the leucemia. Meningeal and bone marrow relapse followed. The subretinal localization responded only to massive systemic steroid treatment. Although asymptomatic, ocular localizations are frequent in leucemia. Their prognostic impact depends on the ocular structure involved and on the chronology of onset--early or late in the leucemia course. The underlying pathophysiological mechanism of ocular involvement remains unexplained but hyperleucocytosis at presentation may be a risk factor and would justify at least systematic specialized examinations and discussion of prophylactic treatment.

  16. American experience in the implementation of AML / CFT system

    Directory of Open Access Journals (Sweden)

    Larin Dmitry


    Full Text Available This article presents a research into very specific matters and issues of creating and further improvement of Anti-Money Laundering and Combating the Financing of Terrorism system (abbreviated as AML/CFT in the USA. In contains a precise analysis of key elements of this system, as well as a deep look into the nature and purposes of financial intelligence “FinCEN”. Strong emphasis is laid on The US Foreign Account Tax Compliance Act (FATCA for the reason that, according to this Act, any foreign financial institution is legitimately forced to sign a special agreement with The US Internal Revenue Service (IRS, giving the Service power to maintain control over any American asset within its equity. The latter is understood as a legal right to investigate not only the accounts and property of American taxpayers, but to investigate any account or capital of any foreign institution having American shares or stocks.

  17. Prenatal origin of childhood AML occurs less frequently than in childhood ALL

    International Nuclear Information System (INIS)

    Burjanivova, Tatiana; Zuna, Jan; Madzo, Jozef; Muzikova, Katerina; Meyer, Claus; Schneider, Bjoern; Votava, Felix; Marschalek, Rolf; Stary, Jan; Trka, Jan


    While there is enough convincing evidence in childhood acute lymphoblastic leukemia (ALL), the data on the pre-natal origin in childhood acute myeloid leukemia (AML) are less comprehensive. Our study aimed to screen Guthrie cards (neonatal blood spots) of non-infant childhood AML and ALL patients for the presence of their respective leukemic markers. We analysed Guthrie cards of 12 ALL patients aged 2–6 years using immunoglobulin (Ig) and T-cell receptor (TCR) gene rearrangements (n = 15) and/or intronic breakpoints of TEL/AML1 fusion gene (n = 3). In AML patients (n = 13, age 1–14 years) PML/RARalpha (n = 4), CBFbeta/MYH11 (n = 3), AML1/ETO (n = 2), MLL/AF6 (n = 1), MLL/AF9 (n = 1) and MLL/AF10 (n = 1) fusion genes and/or internal tandem duplication of FLT3 gene (FLT3/ITD) (n = 2) were used as clonotypic markers. Assay sensitivity determined using serial dilutions of patient DNA into the DNA of a healthy donor allowed us to detect the pre-leukemic clone in Guthrie card providing 1–3 positive cells were present in the neonatal blood spot. In 3 patients with ALL (25%) we reproducibly detected their leukemic markers (Ig/TCR n = 2; TEL/AML1 n = 1) in the Guthrie card. We did not find patient-specific molecular markers in any patient with AML. In the largest cohort examined so far we used identical approach for the backtracking of non-infant childhood ALL and AML. Our data suggest that either the prenatal origin of AML is less frequent or the load of pre-leukemic cells is significantly lower at birth in AML compared to ALL cases

  18. Milch, Milchprodukte, Analoge und Speiseeis (United States)

    Coors, Ursula

    Die Produktpalette Milch und Erzeugnisse aus Milch beinhaltet Konsummilch, die aus Milch oder Bestandteilen der Milch hergestellten Milcherzeugnisse wie Sauermilch-, Joghurt-, Kefir-, Buttermilch-, Sahne-, Kondensmilch-, Trockenmilch- und Molkenerzeugnisse, Milchmisch- und Molkenmischprodukte (Produkte mit beigegebenen Lebensmitteln), Milchzucker, Milcheiweißerzeugnisse, Milchfette und Käse.

  19. Übergewicht und Adipositas in Kindheit und Jugend


    Nitzko, Sina


    Einführend wird auf wesentliche Entwicklungsaspekte der interessierenden Lebensphasen Kindheit und Jugend eingegangen. Im Anschluss daran werden verschiedene Aspekte von Übergewicht und Adipositas in Kindheit und Jugend thematisiert. Neben der Definition und Diagnostik, wird auf Möglichkeiten der Klassifikation sowie die Epidemiologie eingegangen. Dargestellt werden darüber hinaus körperliche und psychische Folgestörungen, welche mit Adipositas assoziiert sein können. Basierend auf der...

  20. [Inhibitory Effect of Decitabine on Proliferation of MDS-L Cells and Its Mechanism]. (United States)

    Wu, Dong; Zhang, Yao; Zhao, You-Shan; Guo, Juan; Chang, Chun-Kang


    To investigate the inhibitory effect of decitabine (DAC) in various dosages on the proliferention of MDS-RAEB cell line MDS-L and its mechanism. LC-MS/MS method was used to test the blood DAC concentration of 2 groups of MDS patients being treated with DAC 20 and 15 mg/m 2 ×5 d. In according to the various blood DAC concentration levels, the MDS-L cells were treated with different DAC dosages for 24, 48, 72 and 96 h, respectively. The CCK-8 method was applied to determine the cell proliferation, the flow cytometry was used to analyze the cell cycle and cell apoptosis changes, the P15 INK4B DNA methylation status was measured by methylation specific PCR using EZ DNA Methylation-Gold Kit. The blood DAC concentration of MDS patients treated with DAC 20 mg/m 2 ×5 d was 174.08±80.15(84.7-311) ng/ml, which was significantly higher than 89.87±32.94(43.2-165)ng/ml for the group treated with 15 mg/m 2 ×5 d (P=0.014). DAC could notably inhibit the proliferation of MDS-L cells, and the effect was in dose- and- time-dependent manner(r=0.786). However, when DAC concentration was ≥0.1 µg/ml, the proliferation inhibition rates were not significantly different between various dosages. After DAC treatment, MDS-L cells in G 1 phase increased notably, while cells in S phase decreased significantly. Also, the P15 INK4B DNA methylation status of MDS-L cells decreased after being treated with DAC for 96 h, but the difference was not significant between various dosages. DAC can significantly suppress MDS-L cell proliferation, block MDS-L cells in G 1 phase and induce the apoptosis at low concentration (0.1-0.2 µg/ml).

  1. Thermodynamik grundlagen und technische anwendungen

    CERN Document Server

    Baehr, Hans Dieter


    Für die aktualisierte 14. Auflage des bewährten Lehrbuchs der Technischen Thermodynamik wurde das Kapitel über Wärmekraftanlagen gründlich bearbeitet und durch einen Abschnitt zur Energiewandlung ergänzt: Die Energiebedarfsstruktur von Deutschland wird erläutert, und die möglichen Energiewandlungspfade werden diskutiert. Schwerpunkt des Buches ist die ausführliche und auch dem Anfänger verständliche Darstellung der Grundlagen der Thermodynamik mit der sorgfältigen Einführung der thermodynamischen Begriffe und den fundamentalen Bilanzgleichungen für Energie, Entropie und Exergie. Die thermodynamischen Eigenschaften reiner Fluide und fluider Gemische werden eingehend erläutert. Darauf aufbauend wird die Thermodynamik der Gemische und der chemischen Reaktionen entwickelt. Auch die thermodynamischen Aspekte wichtiger energie- und verfahrenstechnischer Anwendungen werden praxisnah behandelt: - Strömungs- und Arbeitsprozesse, - thermische Stofftrennverfahren, - Verbrennungsprozesse und Verbrennungsk...

  2. [Establishment of Primary Adult MDS Nested Case-Control Study Cohort and Study of Risk Factors Associated with MDS Evolution to Leukemia]. (United States)

    Ma, Yan; Chen, Bo-Bin; Wang, Xiao-Qin; Xu, Xiao-Ping; Lin, Guo-Wei


    To establish a nested case-control study cohort in myelodysplastic syndrome (MDS) patients and investigate the clinical characteristics, WHO subtype and risk factors associated with MDS evolution to leukemia of this cohort. All patients, ≥18 years of age, provided by 24 Shanghai hospitals with initial clinical findings consistent with a hematopoietic abnormality between June 2003 and April 2007, were the candidates for inclusion in this study. The blood and bone marrow samples of every patient should be provided at baseline. Diagnosis was made by incorporating morphologic, immunophenotypic, cytogenetic and molecular features according to WHO classification criteria. Cytogenetic analysis was performed using conventional G-banding karyotyping and fluorescence in situ hybridization (FISH) techniques. Cumulative risk of evolution was estimated by Kaplan-Meier method. Prognostic factors were evaluated by univariate Log-rank method and multivariate Cox proportional hazard models. A total of 435 patients were diagnosed as MDS. The median age of MDS onset was 58(18-90) years, with 248 male patients and 187 female patients (male: female 1.33: 1). The percentage of cases with refractory cytopenia with multilineage dysplasia (RCMD) was the highest (65.5%), while that of refraetory anemia (RA) (2.3%), refractory anenia with ring sideroblast (RARS) (1.1%) and 5q-syndrome (0.5%) was lower. Trisomy 8 (+8) was the most common chromosome abnormalities (71 cases, 12.7%). The mean follow-up time was 20.3 (4.2-57.1) months. Cases were patients with evolution by the end of follow-up, while controls were patients without evolution by that time. Case group included 41 patients and control group included 342 patients. Univariate analysis showed that the age, sex, WHO subtype, WBC count, absolute neutrophil count (ANC), IPSS cytogenetic subgroup, IPSS group and bone marrow blast percentage were significant risk factors for leukemia-free survival (LFS). Multivariate analysis of COX model

  3. Steuern und Governance

    Directory of Open Access Journals (Sweden)

    Eduard Müller


    Full Text Available ENGLISH: Taxation, in the modern state, has long been a mass phenomenon with an interdisciplinary outlook. On the macro level of the state, a new generation of administrative reforms has crystallized under the label “good public governance”. These reforms seek to resolve regulatory interdependence of state and non - state actors by way of cooperation and interaction. In parallel, on the micro level of businesses, “corporate governance” – voluntary compliance with legal and ethical standards – has become an increasingly important issue. With a view to tax law and tax collection, these developments open up new possibilities to raise tax compliance by means of consensual and cooperative instruments and, accordingly, address taxation as a mass phenomenon. DEUTSCH: Besteuerung ist im modernen Staat ein Massenphänomen und längst interdisziplinär ausgerichtet. Auf der Makro-Ebene des Staates hat sich unter dem Begriff Good Public Governance eine neue Generation von Staats- und Verwaltungsreformen herausgebildet, die Regelungsbeziehungen von staatlichen und nichtstaatlichen Akteuren durch Kooperationen und Interaktionen zu lösen versucht. Parallel dazu hat auf der Mikro-Ebene der Unternehmen mit dem Thema Corporate Governance die freiwillige Einhaltung von rechtlichen und ethischen Regeln an Bedeutung gewonnen. Für das Steuerrecht und den Steuervollzug resultieren aus diesen Entwicklungen neue Möglichkeiten, durch Nutzung konsens- und kooperationsorientierter Instrumente die Tax Compliance zu erhöhen und so dem Massenphänomen Besteuerung gerecht zu werden.

  4. Randomized phase 2 study of low-dose decitabine vs low-dose azacitidine in lower-risk MDS and MDS/MPN. (United States)

    Jabbour, Elias; Short, Nicholas J; Montalban-Bravo, Guillermo; Huang, Xuelin; Bueso-Ramos, Carlos; Qiao, Wei; Yang, Hui; Zhao, Chong; Kadia, Tapan; Borthakur, Gautam; Pemmaraju, Naveen; Sasaki, Koji; Estrov, Zeev; Cortes, Jorge; Ravandi, Farhad; Alvarado, Yesid; Komrokji, Rami; Sekeres, Mikkael A; Steensma, David P; DeZern, Amy; Roboz, Gail; Kantarjian, Hagop; Garcia-Manero, Guillermo


    Hypomethylating agents (HMAs) improve survival in patients with higher-risk myelodysplastic syndromes (MDS) but are less well-studied in lower-risk disease. We compared the safety and efficacy of low-dose decitabine vs low-dose azacitidine in this group of patients. Adults with low- or intermediate 1-risk MDS or MDS/myeloproliferative neoplasm (MPN), including chronic myelomonocytic leukemia, according to the International Prognostic Scoring System, were randomly assigned using a Bayesian adaptive design to receive either azacitidine 75 mg/m 2 intravenously/subcutaneously daily or decitabine 20 mg/m 2 intravenously daily for 3 consecutive days on a 28-day cycle. The primary outcome was overall response rate (ORR). Between November 2012 and February 2016, 113 patients were treated: 40 (35%) with azacitidine and 73 (65%) with decitabine. The median age was 70 years; 81% of patients were intermediate 1-risk patients. The median number of cycles received was 9. The ORRs were 70% and 49% ( P = .03) for patients treated with decitabine and azacitidine, respectively. Thirty-two percent of patients treated with decitabine became transfusion independent compared with 16% of patients treated with azacitidine ( P = .2). Cytogenetic response rates were 61% and 25% ( P = .02), respectively. With a median follow-up of 20 months, the overall median event-free survival was 18 months: 20 and 13 months for patients treated with decitabine and azacitidine, respectively ( P = .1). Treatment was well tolerated, with a 6-week mortality rate of 0%. The use of low-dose HMAs is safe and effective in patients with lower-risk MDS and MDS/MPN. Their effect on the natural history of lower-risk disease needs to be further studied. This trial was registered at (identifier NCT01720225). © 2017 by The American Society of Hematology.

  5. Osteoporose und Laktoseintoleranz

    Directory of Open Access Journals (Sweden)

    Obermayer-Pietsch B


    Full Text Available Laktosemalabsorption oder Laktoseintoleranz ist eine symptomatische Unverträglichkeit von Milchzucker (Laktose, zumeist aufgrund einer autosomal rezessiv erblichen, irreversiblen Abnahme des Enzyms Laktase im Jugendalter, die bei etwa der Hälfte der Weltbevölkerung auftritt. Die Betroffenen meiden oft instinktiv Milch und Milchprodukte wegen der damit verbundenen Malabsorptions-Symptome. Damit scheiden diese Nahrungsmittel aber auch als Kalziumlieferanten aus und es kann zu einer Mangelversorgung des Knochens mit Kalzium und damit zu Osteoporose kommen. Da in Österreich etwa 20–25 % der Bevölkerung betroffen sind, ist diese Stoffwechselveränderung nicht zu vernachlässigen. Diagnostische und begleitende ernährungsmedizinische Maßnahmen und gegebenenfalls eine osteotrope Therapie sollten zum Erhalt der Knochenmasse eingesetzt werden.

  6. Neuausrichtung und Konsolidierung (United States)

    Grohmann, Heinz

    Mit der Wahl von Wolfgang Wetzel zum Vorsitzenden der Deutschen Statistischen Gesellschaft im Jahre 1972 begann eine 32jährige Ära, in der die praktische und die theoretische Statistik in einem ausgewogenen Verhältnis gepflegt wurden. Ein regelmäßiger vierjähriger Wechsel im Vorsitz stärkte die Gemeinschaft und die praktische wie die wissenschaftliche Arbeit gleichermaßen. Die jährlichen Hauptversammlungen behandelten gesellschaftlich aktuelle wie zukunftsorientierte Themen, und die Ausschüsse sowie weitere Veranstaltungen gaben Gelegenheit zur Förderung und Pflege einer Vielzahl von Arbeitsgebieten der Statistik. Darüber wird nicht nur in diesem Kapitel, sondern auch in den Teilen II und III des Bandes berichtet.

  7. Studies on the tumor initiation/promotion potential of six middle distillates (MDs) in mouse skin. (United States)

    Jungen, H; Mellert, W; Wenzel-Hartung, R


    Six middle distillates (MDs) were tested for tumor initiating/promoting activity after application to the skin of 30 male CD-1 (ICR) BR mice per group. As the control, 7,12-dimethylbenz[a]-anthracene (DMBA) was used for initiation followed by 12-O-tetradecanoylphorbol-13-acetate (TPA) for promotion. For assessing the tumor-initiating activity, 50 microliters of neat MDs was administered for 5 days with subsequent TPA promotion. In the promotion bioassay, after DMBA initiation 50 microliters of the neat MDs was administered twice weekly until Week 28. For the examination of complete carcinogenic activity, one MD was given without DMBA initiation. Hyperkeratosis, hyperplasia, and dermal inflammation, occurring during the initiation with the MDs, were completely reversible during the 2-week treatment-free period after initiation. Similar skin findings were observed during promotion with the MDs. Regarding the number of affected animals and the severity of the response, TPA was more irritating than the MDs. The initiation study revealed skin tumors for the DMBA/TPA control (30/30), MD 57,389 (14/30), MD 57,396 (5/30), MD 57,383 (4/30) and MD 57,324 (2/30). The promotion study revealed tumor induction by MDs 57,389 (9/30), 57,324 (1/30), 57,393 (1/30), and 57,396 (1/30). Two of 30 animals treated with MD 57,389 developed tumors without DMBA initiation thus indicating that it also is a complete carcinogen. MD 57,399 caused neither initiating nor promoting effects. The tumors observed were diagnosed histopathologically predominantly as squamous cell papillomas.(ABSTRACT TRUNCATED AT 250 WORDS)

  8. MDS-associated somatic mutations and clonal hematopoiesis are common in idiopathic cytopenias of undetermined significance. (United States)

    Kwok, Brian; Hall, Jeff M; Witte, John S; Xu, Yin; Reddy, Prashanti; Lin, Keming; Flamholz, Rachel; Dabbas, Bashar; Yung, Aine; Al-Hafidh, Jenan; Balmert, Emily; Vaupel, Christine; El Hader, Carlos; McGinniss, Matthew J; Nahas, Shareef A; Kines, Julie; Bejar, Rafael


    Establishing a diagnosis in patients suspected of having a myelodysplastic syndrome (MDS) can be challenging and could be informed by the identification of somatic mutations. We performed a prospective study to examine the frequency and types of mutations encountered in 144 patients with unexplained cytopenias. Based on bone marrow findings, 17% were diagnosed with MDS, 15% with idiopathic cytopenias of undetermined significance (ICUS) and some evidence of dysplasia, and 69% with ICUS and no dysplasia. Bone marrow DNA was sequenced for mutations in 22 frequently mutated myeloid malignancy genes. Somatic mutations were identified in 71% of MDS patients, 62% of patients with ICUS and some dysplasia, and 20% of ICUS patients and no dysplasia. In total, 35% of ICUS patients carried a somatic mutation or chromosomal abnormality indicative of clonal hematopoiesis. We validated these results in a cohort of 91 lower-risk MDS and 249 ICUS cases identified over a 6-month interval. Mutations were found in 79% of those with MDS, in 45% of those with ICUS with dysplasia, and in 17% of those with ICUS without dysplasia. The spectrum of mutated genes was similar with the exception of SF3B1 which was rarely mutated in patients without dysplasia. Variant allele fractions were comparable between clonal ICUS (CCUS) and MDS as were mean age and blood counts. We demonstrate that CCUS is a more frequent diagnosis than MDS in cytopenic patients. Clinical and mutational features are similar in these groups and may have diagnostic utility once outcomes in CCUS patients are better understood. © 2015 by The American Society of Hematology.

  9. SETBP1 mutations drive leukemic transformation in ASXL1-mutated MDS. (United States)

    Inoue, D; Kitaura, J; Matsui, H; Hou, H-A; Chou, W-C; Nagamachi, A; Kawabata, K C; Togami, K; Nagase, R; Horikawa, S; Saika, M; Micol, J-B; Hayashi, Y; Harada, Y; Harada, H; Inaba, T; Tien, H-F; Abdel-Wahab, O; Kitamura, T


    Mutations in ASXL1 are frequent in patients with myelodysplastic syndrome (MDS) and are associated with adverse survival, yet the molecular pathogenesis of ASXL1 mutations (ASXL1-MT) is not fully understood. Recently, it has been found that deletion of Asxl1 or expression of C-terminal-truncating ASXL1-MTs inhibit myeloid differentiation and induce MDS-like disease in mice. Here, we find that SET-binding protein 1 (SETBP1) mutations (SETBP1-MT) are enriched among ASXL1-mutated MDS patients and associated with increased incidence of leukemic transformation, as well as shorter survival, suggesting that SETBP1-MT play a critical role in leukemic transformation of MDS. We identify that SETBP1-MT inhibit ubiquitination and subsequent degradation of SETBP1, resulting in increased expression. Expression of SETBP1-MT, in turn, inhibited protein phosphatase 2A activity, leading to Akt activation and enhanced expression of posterior Hoxa genes in ASXL1-mutant cells. Biologically, SETBP1-MT augmented ASXL1-MT-induced differentiation block, inhibited apoptosis and enhanced myeloid colony output. SETBP1-MT collaborated with ASXL1-MT in inducing acute myeloid leukemia in vivo. The combination of ASXL1-MT and SETBP1-MT activated a stem cell signature and repressed the tumor growth factor-β signaling pathway, in contrast to the ASXL1-MT-induced MDS model. These data reveal that SETBP1-MT are critical drivers of ASXL1-mutated MDS and identify several deregulated pathways as potential therapeutic targets in high-risk MDS.

  10. Telomere dynamics in patients with del (5q) MDS before and under treatment with lenalidomide. (United States)

    Beier, Fabian; Masouleh, Behzad Kharabi; Buesche, Guntram; Ventura Ferreira, Monica S; Schneider, Rebekka K; Ziegler, Patrick; Wilop, Stefan; Vankann, Lucia; Gattermann, Norbert; Platzbecker, Uwe; Giagounidis, Aristoteles; Götze, Katharina S; Nolte, Florian; Hofmann, Wolf-Karsten; Haase, Detlef; Kreipe, Hans; Panse, Jens; Blasco, Maria A; Germing, Ulrich; Brümmendorf, Tim H


    Myelodysplastic syndrome (MDS) associated with an acquired, isolated deletion of chromosome 5q (del (5q) MDS), represent a clonal disorder of hematopoiesis and a clinically distinct entity of MDS. Treatment of del (5q) MDS with the drug lenalidomide has significantly improved quality of life leading to transfusion independence and complete cytogenetic response rates (CCR) in the majority of patients. Telomeres are located at the end of eukaryotic chromosomes and are linked to replicative history/potential as well as genetic (in) stability of hematopoietic stem cells. Here, we analyzed telomere length (TL) dynamics before and under lenalidomide treatment in the peripheral blood and/or bone marrow of del (5q) patients enrolled in the LEMON-5 study (NCT01081431). Hematopoietic cells from del (5q) MDS patients were characterized by significantly shortened TL compared to age-matched healthy controls. Telomere loss was more accelerated in patients with longer disease duration (>2 years) and more pronounced cytopenias. Sequential analysis under lenalidomide treatment revealed that previously shortened TL in peripheral blood cells was significantly "elongated" towards normal levels within the first six months suggesting a shift from clonal del (5q) cells towards normal hematopoiesis in lenalidomide treated MDS patients. Taken together our findings suggest that the development of the del (5q) clone is associated with accelerated telomere shortening at diagnosis. However, upon induction of CCR and reoccurrence of normal hematopoiesis, the lack of a persistent TL deficit argues against telomere-mediated genetic instability neither as a disease-promoting event of del (5q) MDS nor for lenalidomide mediated development of secondary primary malignancies of the hematopoietic system in responding patients. Copyright © 2015 Elsevier Ltd. All rights reserved.

  11. Rapid expansion of preexisting nonleukemic hematopoietic clones frequently follows induction therapy for de novo AML. (United States)

    Wong, Terrence N; Miller, Christopher A; Klco, Jeffery M; Petti, Allegra; Demeter, Ryan; Helton, Nichole M; Li, Tiandao; Fulton, Robert S; Heath, Sharon E; Mardis, Elaine R; Westervelt, Peter; DiPersio, John F; Walter, Matthew J; Welch, John S; Graubert, Timothy A; Wilson, Richard K; Ley, Timothy J; Link, Daniel C


    There is interest in using leukemia-gene panels and next-generation sequencing to assess acute myelogenous leukemia (AML) response to induction chemotherapy. Studies have shown that patients with AML in morphologic remission may continue to have clonal hematopoiesis with populations closely related to the founding AML clone and that this confers an increased risk of relapse. However, it remains unknown how induction chemotherapy influences the clonal evolution of a patient's nonleukemic hematopoietic population. Here, we report that 5 of 15 patients with genetic clearance of their founding AML clone after induction chemotherapy had a concomitant expansion of a hematopoietic population unrelated to the initial AML. These populations frequently harbored somatic mutations in genes recurrently mutated in AML or myelodysplastic syndromes and were detectable at very low frequencies at the time of AML diagnosis. These results suggest that nonleukemic hematopoietic stem and progenitor cells, harboring specific aging-acquired mutations, may have a competitive fitness advantage after induction chemotherapy, expand, and persist long after the completion of chemotherapy. Although the clinical importance of these "rising" clones remains to be determined, it will be important to distinguish them from leukemia-related populations when assessing for molecular responses to induction chemotherapy. © 2016 by The American Society of Hematology.

  12. The Proteasome Inhibitor Bortezomib Sensitizes AML with Myelomonocytic Differentiation to TRAIL Mediated Apoptosis

    Energy Technology Data Exchange (ETDEWEB)

    Dijk, Marianne van; Murphy, Eoin [Apoptosis Research Center, National University of Ireland, University Road, Galway (Ireland); School of Natural Sciences, National University of Ireland, University Road, Galway (Ireland); Morrell, Ruth [Apoptosis Research Center, National University of Ireland, University Road, Galway (Ireland); School of Natural Sciences, National University of Ireland, University Road, Galway (Ireland); School of Medicine, National University of Ireland, University Road, Galway (Ireland); Knapper, Steven [Department of Haematology, School of Medicine, Cardiff University, Heath Park, CF14 4XN Cardiff (United Kingdom); O' Dwyer, Michael [Apoptosis Research Center, National University of Ireland, University Road, Galway (Ireland); School of Medicine, National University of Ireland, University Road, Galway (Ireland); Samali, Afshin; Szegezdi, Eva, E-mail: [Apoptosis Research Center, National University of Ireland, University Road, Galway (Ireland); School of Natural Sciences, National University of Ireland, University Road, Galway (Ireland)


    Acute myeloid leukemia (AML) is an aggressive stem cell malignancy that is difficult to treat. There are limitations to the current treatment regimes especially after disease relapse, and therefore new therapeutic agents are urgently required which can overcome drug resistance whilst avoiding unnecessary toxicity. Among newer targeted agents, both tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) and proteasome inhibitors show particular promise. In this report we show that a combination of the proteasome inhibitor bortezomib and TRAIL is effective against AML cell lines, in particular, AML cell lines displaying myelomonocytic/monocytic phenotype (M4/M5 AML based on FAB classification), which account for 20-30% of AML cases. We show that the underlying mechanism of sensitization is at least in part due to bortezomib mediated downregulation of c-FLIP and XIAP, which is likely to be regulated by NF-κB. Blockage of NF-κB activation with BMS-345541 equally sensitized myelomonocytic AML cell lines and primary AML blasts to TRAIL.

  13. MDS-UPDRS to assess non-motor symptoms after STN DBS for Parkinson's disease. (United States)

    Jafari, Nickey; Pahwa, Rajesh; Nazzaro, Jules M; Arnold, Paul M; Lyons, Kelly E


    To determine if the non-motor sections of the Movement Disorder Society's (MDS) version of the Unified Parkinson's Disease Rating Scale (UPDRS) could supplement the original UPDRS as a patient completed assessment of changes in non-motor symptoms in Parkinson's disease (PD) patients after bilateral subthalamic nucleus (STN) deep brain stimulation (DBS). Thirty PD patients who underwent bilateral STN DBS were assessed using the total UPDRS and the non-motor sections of the MDS-UPDRS prior to surgery and one year following surgery. This study focuses on non-motor symptoms as assessed by Part I of the UPDRS and Part 1A and 1B of the MDS-UPDRS. One year following surgery, no individual non-motor symptoms or the total mentation score of the UPDRS were significantly changed. In comparison, the MDS-UPDRS showed significant improvements in sleep and urinary problems and a trend towards improvement in anxiety, constipation, daytime sleepiness, fatigue and pain. This study provides evidence that the MDS-UPDRS non-motor sections, when completed by the patients, can supplement the original version of the UPDRS as an effective method of measuring changes in non-motor symptoms after DBS. It also reinforces the benefits of bilateral STN DBS on non-motor symptoms of PD.

  14. Incorporating novel approaches in the management of MDS beyond conventional hypomethylating agents. (United States)

    Odenike, Olatoyosi


    In the last decade, the treatment of higher-risk myelodysplastic syndromes (MDS) has revolved around the azanucleosides, azacitidine and decitabine, which at lower doses are postulated to work predominantly via their effects on inhibition of DNA methyltransferases and consequent DNA hypomethylation. For patients who relapse after, or do not respond to, hypomethylating agent therapy, the outcome is dismal, and new agents and approaches that have the potential to alter the natural history of these diseases are desperately needed. Allogeneic stem cell transplant is the only known potentially curative approach in MDS, but its applicability has been limited by the advanced age of patients and attendant comorbidities. There is now an increasing array of new agents under clinical investigation in MDS that aim to exploit our expanding understanding of molecular pathways that are important in the pathogenesis of MDS. This review focuses on a critical appraisal of novel agents being evaluated in higher-risk MDS that go beyond the conventional hypomethylating agent therapies approved by the US Food and Drug Administration. © 2016 by The American Society of Hematology. All rights reserved.

  15. [TOPICS-MDS: a versatile resource for generating scientific and social knowledge for elderly care]. (United States)

    van den Brink, Danielle; Lutomski, Jennifer E; Qin, Li; den Elzen, Wendy P J; Kempen, Gertrudis I J M; Krabbe, Paul F M; Steyerberg, Ewout W; Muntinga, Maaike; Moll van Charante, Eric P; Bleijenberg, Nienke; Olde Rikkert, Marcel G M; Melis, René J F


    Developed as part of the National Care for the Elderly Programme (NPO), TOPICS-MDS is a uniform, national database on the health and wellbeing of the older persons and caregivers who participated in NPO-funded projects. TOPICS-MDS Consortium has gained extensive experience in constructing a standardized questionnaire to collect relevant health care data on quality of life, health services utilization, and informal care use. A proactive approach has been undertaken not only to ensure the standardization and validation of instruments but also the infrastructure for external data requests. Efforts have been made to promote scientifically and socially responsible use of TOPICS-MDS; data has been available for secondary use since early 2014. Through this data sharing initiative, researchers can explore health issues in a broader framework which may have not been possible within individual NPO projects; this broader framework is highly relevant for influencing health policy. In this article, we provide an overview of the development and on-going progress of TOPICS-MDS. We further describe how information derived from TOPICS-MDS can be applied to facilitate future scientific innovations and public health initiatives to improve care for frail older persons and their caregivers.

  16. Mutational profiling in patients with MDS: ready for every-day use in the clinic? (United States)

    Bacher, Ulrike; Kohlmann, Alexander; Haferlach, Torsten


    Multiple recurrent somatic mutations were identified in the majority of patients with myelodysplastic syndromes (MDS), but investigating the broad spectrum of molecular markers in MDS exceeds many laboratories' capacity when traditional molecular techniques are used. High-throughput second generation sequencing (=next-generation sequencing, NGS) has proven to be applicable for comprehensive biomarker mutation analyses allowing to increase diagnostic sensitivity and accuracy and to improve risk stratification and prognostication in addition to cytomorphology and cytogenetic analysis in patients with MDS. Amplicon deep-sequencing enables comprehensive biomarker analysis in a multitude of patients per investigation in an acceptable turn-around time and at affordable costs. Comprehensive myeloid marker panels were successfully introduced into diagnostic practice. Therefore, molecular mutation analysis is ready for use in all patients with suspected MDS, may contribute to risk stratification in possible candidates for allogeneic stem cell transplantation, and should become an integral part of clinical research studies in MDS patients. Copyright © 2014 Elsevier Ltd. All rights reserved.

  17. Teilchendetektoren Grundlagen und Anwendungen

    CERN Document Server

    Kolanoski, Hermann


    In diesem Buch werden die experimentellen Grundlagen von Teilchendetektoren und ihre Anwendung in Experimenten beschrieben. Die Entwicklung von Detektoren ist ein wichtiger Bestandteil der Teilchen-, Astroteilchen- und Kernphysik und gehört daher zum Handwerk des Experimentalphysikers in diesen Gebieten. Dieses umfassende Werk beinhaltet den kompletten Stoff für entsprechende Master-Module in der experimentellen Teilchenphysik, geht aber im Inhalt auch darüber hinaus. Zielgruppe sind Studierende, die sich in die Materie vertiefen möchten, aber auch Lehrende und Wissenschaftler, die das Buch zum Einstieg in das wissenschaftliche Arbeiten an Detektorentwicklungen verwenden können. Zielrichtung des Buches ist, die physikalischen Grundlagen für die Detektoren und ihrer verschiedenen Ausführungen so klar wie möglich und so tiefgehend wie nötig darzustellen. Die Breite des für die Detektorentwicklung nötigen Wissens umfasst viele Bereiche der Physik und Technik, von den Wechselwirkun...

  18. Mediendidaktik und Wissensmanagement

    Directory of Open Access Journals (Sweden)

    Gabi Reinmann-Rothmeier


    Full Text Available Mediendidaktik und Wissensmanagement – das ist auf den ersten Blick ein ungleiches Paar: Die Mediendidaktik ist eine Teildisziplin der (Medien- Pädagogik, während Wissensmanagement ein genuin wirtschaftliches Thema mit betriebswirtschaftlichen Akzenten ist. Annäherungen zwischen der Mediendidaktik und Wissensmanagement gibt es zum einen durch den sog. E-Learning-Trend seitens der Wirtschaft, der mediendidaktisches Wissen und Können auf den Plan ruft, zum anderen durch wachsendes Interesse am Thema Wissensmanagement seitens der Pädagogik. Der Beitrag beschreibt sowohl für das E-Learning als auch für das Wissensmanagement aus pädagogisch-psychologischer Sicht jeweils ein Orientierungsmodell; beide Modelle machen die Berührungspunkte zwischen Mediendidaktik und Wissensmanagement deutlich. Neben einem Überblick über wirtschaftliche Argumente für eine Verschmelzung von E-Learning und Wissensmanagement werden aufbauend auf den beiden Orientierungsmodellen theoretische und praktische Verbindungslinien zwischen E-Learning und Wissensmanagement sowie die Rolle der Mediendidaktik in dem daraus entstehenden Wechselverhältnis herausgearbeitet.

  19. Lessing und der Islam


    Muslim, Zahim Mohammed


    „Lessing und der Islam“ beschäftigt sich unparteiisch mit Lessings Auseinandersetzung mit dem Islam. Die Arbeit setzt sich das Ziel, den Leser und den Literaturkennern sowie der deutschen Bibliothek der Germanistik etwas von Lessings Auseinandersetzung mit dem Islam in die Hand zu geben, die bis heute als großes Modell für die interkulturelle und interreligiöse Menschheitstoleranzdebatte im Gedächtnis der deutschen Literatur vorhanden ist. Im ersten Teil widmet sich die vorliegende Arbeit de...

  20. Trauma und Terror


    Szyszkowitz, T. (Tessa)


    1. Einleitung Ausgehend von der Fragestellung, warum gerade bei Tschetschenen und Palästinensern der Selbstmordterrorismus in den letzten Jahren so populär geworden ist, analysiert die Autorin die Geschichte dieser beiden Völker. Einer der Gründe ist bisher wenig beachtet worden. Der Einfluss eines kollektiven Traumas, das als solches nicht anerkannt, behandelt und auch nicht einer politischen Lösung zugeführt wurde. 2. Geschichte der Palästinenser und Tschetschenen Im Zuge der Err...

  1. The Mice Drawer System (MDS experiment and the space endurance record-breaking mice.

    Directory of Open Access Journals (Sweden)

    Ranieri Cancedda

    Full Text Available The Italian Space Agency, in line with its scientific strategies and the National Utilization Plan for the International Space Station (ISS, contracted Thales Alenia Space Italia to design and build a spaceflight payload for rodent research on ISS: the Mice Drawer System (MDS. The payload, to be integrated inside the Space Shuttle middeck during transportation and inside the Express Rack in the ISS during experiment execution, was designed to function autonomously for more than 3 months and to involve crew only for maintenance activities. In its first mission, three wild type (Wt and three transgenic male mice over-expressing pleiotrophin under the control of a bone-specific promoter (PTN-Tg were housed in the MDS. At the time of launch, animals were 2-months old. MDS reached the ISS on board of Shuttle Discovery Flight 17A/STS-128 on August 28(th, 2009. MDS returned to Earth on November 27(th, 2009 with Shuttle Atlantis Flight ULF3/STS-129 after 91 days, performing the longest permanence of mice in space. Unfortunately, during the MDS mission, one PTN-Tg and two Wt mice died due to health status or payload-related reasons. The remaining mice showed a normal behavior throughout the experiment and appeared in excellent health conditions at landing. During the experiment, the mice health conditions and their water and food consumption were daily checked. Upon landing mice were sacrificed, blood parameters measured and tissues dissected for subsequent analysis. To obtain as much information as possible on microgravity-induced tissue modifications, we organized a Tissue Sharing Program: 20 research groups from 6 countries participated. In order to distinguish between possible effects of the MDS housing conditions and effects due to the near-zero gravity environment, a ground replica of the flight experiment was performed at the University of Genova. Control tissues were collected also from mice maintained on Earth in standard vivarium cages.

  2. The Mice Drawer System (MDS) experiment and the space endurance record-breaking mice. (United States)

    Cancedda, Ranieri; Liu, Yi; Ruggiu, Alessandra; Tavella, Sara; Biticchi, Roberta; Santucci, Daniela; Schwartz, Silvia; Ciparelli, Paolo; Falcetti, Giancarlo; Tenconi, Chiara; Cotronei, Vittorio; Pignataro, Salvatore


    The Italian Space Agency, in line with its scientific strategies and the National Utilization Plan for the International Space Station (ISS), contracted Thales Alenia Space Italia to design and build a spaceflight payload for rodent research on ISS: the Mice Drawer System (MDS). The payload, to be integrated inside the Space Shuttle middeck during transportation and inside the Express Rack in the ISS during experiment execution, was designed to function autonomously for more than 3 months and to involve crew only for maintenance activities. In its first mission, three wild type (Wt) and three transgenic male mice over-expressing pleiotrophin under the control of a bone-specific promoter (PTN-Tg) were housed in the MDS. At the time of launch, animals were 2-months old. MDS reached the ISS on board of Shuttle Discovery Flight 17A/STS-128 on August 28(th), 2009. MDS returned to Earth on November 27(th), 2009 with Shuttle Atlantis Flight ULF3/STS-129 after 91 days, performing the longest permanence of mice in space. Unfortunately, during the MDS mission, one PTN-Tg and two Wt mice died due to health status or payload-related reasons. The remaining mice showed a normal behavior throughout the experiment and appeared in excellent health conditions at landing. During the experiment, the mice health conditions and their water and food consumption were daily checked. Upon landing mice were sacrificed, blood parameters measured and tissues dissected for subsequent analysis. To obtain as much information as possible on microgravity-induced tissue modifications, we organized a Tissue Sharing Program: 20 research groups from 6 countries participated. In order to distinguish between possible effects of the MDS housing conditions and effects due to the near-zero gravity environment, a ground replica of the flight experiment was performed at the University of Genova. Control tissues were collected also from mice maintained on Earth in standard vivarium cages.

  3. Parkinson's disease severity levels and MDS-Unified Parkinson's Disease Rating Scale. (United States)

    Martínez-Martín, Pablo; Rodríguez-Blázquez, Carmen; Mario Alvarez; Arakaki, Tomoko; Arillo, Víctor Campos; Chaná, Pedro; Fernández, William; Garretto, Nélida; Martínez-Castrillo, Juan Carlos; Rodríguez-Violante, Mayela; Serrano-Dueñas, Marcos; Ballesteros, Diego; Rojo-Abuin, Jose Manuel; Chaudhuri, Kallol Ray; Merello, Marcelo


    Severity of PD is usually assessed by means of the motor and disability-based Hoehn and Yahr staging (HY), or clinician and patient global perceptions. Scores of more detailed assessments, as the MDS-UPDRS, have not been translated to a grading that allows assignment of score sections to severity levels. The objective of the present study is to determine cut-off points for PD severity levels based on the MDS-UPDRS. International, observational study. Applied assessments were: HY, MDS-UPDRS, Clinical Impression for Severity Index, and Clinical and Patient Global Impression of Severity. The coincidence in severity level (mild, moderate, severe) of at least two clinical classifications plus the patient's gradation was considered "the criterion of severity". Cut-off values for each MDS-UPDRS subscale was determined by triangulation of: 1) percentile 90 of the subscale total score; 2) receiver operating characteristic (ROC) analysis; and 3) ordinal logistic regression (OLR) model. Sample was composed of 452 consecutive PD patients without dementia, 55.3% males, age 65.1 ± 10.7 years and PD duration 8.7 ± 6.3 years. All HY stages were represented. The "criterion", classified 275 patients (60.8% of the sample) as: mild PD, 149 (54.2%); moderate, 82 (29.8%); and severe, 44 (16%). The following MDS-UPDRS cut-off points between mild/moderate and moderate/severe levels were found: Part 1: 10/11 and 21/22; Part 2: 12/13 and 29/30; Part 3: 32/33 and 58/59; and Part 4: 4/5 and 12/13. Cut-off points to classify PD patients as mild, moderate, or severe on the basis of their MDS-UPDRS scores are proposed. Copyright © 2014 Elsevier Ltd. All rights reserved.

  4. SF3B1-initiating mutations in MDS-RSs target lymphomyeloid hematopoietic stem cells. (United States)

    Mortera-Blanco, Teresa; Dimitriou, Marios; Woll, Petter S; Karimi, Mohsen; Elvarsdottir, Edda; Conte, Simona; Tobiasson, Magnus; Jansson, Monika; Douagi, Iyadh; Moarii, Matahi; Saft, Leonie; Papaemmanuil, Elli; Jacobsen, Sten Eirik W; Hellström-Lindberg, Eva


    Mutations in the RNA splicing gene SF3B1 are found in >80% of patients with myelodysplastic syndrome with ring sideroblasts (MDS-RS). We investigated the origin of SF3B1 mutations within the bone marrow hematopoietic stem and progenitor cell compartments in patients with MDS-RS. Screening for recurrently mutated genes in the mononuclear cell fraction revealed mutations in SF3B1 in 39 of 40 cases (97.5%), combined with TET2 and DNMT3A in 11 (28%) and 6 (15%) patients, respectively. All recurrent mutations identified in mononuclear cells could be tracked back to the phenotypically defined hematopoietic stem cell (HSC) compartment in all investigated patients and were also present in downstream myeloid and erythroid progenitor cells. While in agreement with previous studies, little or no evidence for clonal ( SF3B1 mutation) involvement could be found in mature B cells, consistent involvement at the pro-B-cell progenitor stage was established, providing definitive evidence for SF3B1 mutations targeting lymphomyeloid HSCs and compatible with mutated SF3B1 negatively affecting lymphoid development. Assessment of stem cell function in vitro as well as in vivo established that only HSCs and not investigated progenitor populations could propagate the SF3B1 mutated clone. Upon transplantation into immune-deficient mice, SF3B1 mutated MDS-RS HSCs differentiated into characteristic ring sideroblasts, the hallmark of MDS-RS. Our findings provide evidence of a multipotent lymphomyeloid HSC origin of SF3B1 mutations in MDS-RS patients and provide a novel in vivo platform for mechanistically and therapeutically exploring SF3B1 mutated MDS-RS. © 2017 by The American Society of Hematology.

  5. Time-dependent changes in mortality and transformation risk in MDS. (United States)

    Pfeilstöcker, Michael; Tuechler, Heinz; Sanz, Guillermo; Schanz, Julie; Garcia-Manero, Guillermo; Solé, Francesc; Bennett, John M; Bowen, David; Fenaux, Pierre; Dreyfus, Francois; Kantarjian, Hagop; Kuendgen, Andrea; Malcovati, Luca; Cazzola, Mario; Cermak, Jaroslav; Fonatsch, Christa; Le Beau, Michelle M; Slovak, Marilyn L; Levis, Alessandro; Luebbert, Michael; Maciejewski, Jaroslaw; Machherndl-Spandl, Sigrid; Magalhaes, Silvia M M; Miyazaki, Yasushi; Sekeres, Mikkael A; Sperr, Wolfgang R; Stauder, Reinhard; Tauro, Sudhir; Valent, Peter; Vallespi, Teresa; van de Loosdrecht, Arjan A; Germing, Ulrich; Haase, Detlef; Greenberg, Peter L


    In myelodysplastic syndromes (MDSs), the evolution of risk for disease progression or death has not been systematically investigated despite being crucial for correct interpretation of prognostic risk scores. In a multicenter retrospective study, we described changes in risk over time, the consequences for basal prognostic scores, and their potential clinical implications. Major MDS prognostic risk scoring systems and their constituent individual predictors were analyzed in 7212 primary untreated MDS patients from the International Working Group for Prognosis in MDS database. Changes in risk of mortality and of leukemic transformation over time from diagnosis were described. Hazards regarding mortality and acute myeloid leukemia transformation diminished over time from diagnosis in higher-risk MDS patients, whereas they remained stable in lower-risk patients. After approximately 3.5 years, hazards in the separate risk groups became similar and were essentially equivalent after 5 years. This fact led to loss of prognostic power of different scoring systems considered, which was more pronounced for survival. Inclusion of age resulted in increased initial prognostic power for survival and less attenuation in hazards. If needed for practicability in clinical management, the differing development of risks suggested a reasonable division into lower- and higher-risk MDS based on the IPSS-R at a cutoff of 3.5 points. Our data regarding time-dependent performance of prognostic scores reflect the disparate change of risks in MDS subpopulations. Lower-risk patients at diagnosis remain lower risk whereas initially high-risk patients demonstrate decreasing risk over time. This change of risk should be considered in clinical decision making. © 2016 by The American Society of Hematology.

  6. Prognostic classification of MDS is improved by the inclusion of FISH panel testing with conventional cytogenetics. (United States)

    Kokate, Prajakta; Dalvi, Rupa; Koppaka, Neeraja; Mandava, Swarna


    Cytogenetics is a critical independent prognostic factor in myelodysplastic syndromes (MDS). Conventional cytogenetics (CC) and Fluorescence in situ hybridization (FISH) Panel Testing are extensively used for the prognostic stratification of MDS, although the FISH test is not yet a bona fide component of the International Prognostic Scoring System (IPSS). The present study compares the utility of CC and FISH to detect chromosomal anomalies and in prognostic categorization. GTG-Banding and FISH Panel Testing specifically for -5/-5q, -7/-7q, +8 and -20q was performed on whole blood or bone marrow samples from 136 patients with MDS. Chromosomal anomalies were found in 40 cases by CC, including three novel translocations. FISH identified at least one anomaly in 54/136 (39.7%) cases. More than one anomaly was found in 18/54 (33.3%) cases, therefore, overall FISH identified 75 anomalies of which 32 (42.6%) were undetected by CC. FISH provided additional information in cases with CC failure and in cases with a normal karyotype. Further, in ten cases with an abnormal karyotype, FISH could identify additional anomalies, increasing the number of abnormalities per patient. Although CC is the gold standard in the cytogenetic profiling of MDS, FISH has proven to be an asset in identifying additional abnormalities. The number of anomalies per patient can predict the prognosis in MDS and hence, FISH contributed towards prognostic re-categorization. The FISH Panel testing should be used as an adjunct to CC, irrespective of the adequacy of the number of metaphases in CC, as it improves the prognostic classification of MDS. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. [Changes of CD34(+) and CD71(+)CD45(-) cell levels in bone marrow of MDS and AA patients]. (United States)

    Yan, Zhen-Yu; Tian, Xu; Li, Ying; Yang, Mei-Rong; Zhang, Song; Wang, Xie-Ming; Zhang, Hai-Xia; Cheng, Nai-Yao


    This study was aimed to investigate the changes of CD34(+) and CD71(+)CD45(-) cell levels in MDS and AA patients. A total of 25 cases MDS and 43 cases of AA (18 cases SAA and 25 cases of NSAA) from January 2010 to October 2013 in the Department of Hematology, affiliated hospital of Hebei United University were enrolled in this study. The complete blood count, bone marrow smears, bone marrow biopsy, karyotype analysis and bone marrow blood cell immune genotyping (mainly the proportion of CD34(+) cells, CD71(+)CD45(-) cells in nucleated cells) were carried out for all patients; the changes of CD34(+) and CD71(+)CD45(-) cell levels in patients with MDS and AA (SAA NSAA) were compared; the differences of white blood cell count, platelet count and hemoglobin concentration in patients with count of CD71(+)CD45(-) ≥ 15% or MDS group was higher than that in AA (NSAA and SAA) group (P MDS group was higher than that in SAA (P MDS group. In MDS group with CD71(+)CD45(-) ≥ 15%, the platelet count was significantly higher than that in NSAA group (P MDS and NSAA group with CD71(+)CD45(-) 0.05). It is concluded that the count of CD34(+) cells in MDS patients is significantly higher than that in AA and SAA patients. The count of CD71(+)CD45(-) cells in MDS group is significantly higher than that of SAA group. The platelet count in MDS patients with CD71(+)CD45(-) cells ≥ 15% is significantly higher than that of the NSAA group.

  8. Integration, Informationslogistik und Architektur


    Turowski, Klaus


    Integration, Informationslogistik und Architektur : DW2006 ; 21./22.09.2006 in Friedrichshafen, Germany / Klaus Turowski ... (Hrsg.). - Bonn : Ges. für Informatik, 2006. - 490 S. - (GI-Edition / Proceedings ; 90)

  9. Supraleitung Grundlagen und Anwendungen

    CERN Document Server

    Buckel, Werner


    Seit nunmehr drei Jahrzehnten ist der "Buckel" das Referenzwerk in deutscher Sprache zum Thema Supraleitung. Immer wieder aktualisiert, hat das Lehrbuch Generationen von Studenten begleitet. In der 6., vollständig überarbeiteten Auflage wird das bewährte didaktische Konzept beibehalten, inhaltlich wurde der Band dem aktuellen Stand von Forschung und Technik angepasst. Das Autorenteam um Prof. Kleiner verzichtet auf komplizierte mathematische Herleitungen. Es baut ganz auf das bewährte Step-by-Step-Prinzip: Der Schwierigkeitsgrad wird von Kapitel zu Kapitel gesteigert. So können auch Einsteiger ohne einschlägige Vorkenntnisse dem Stoff bequem folgen. Dank seiner klaren Sprache und zahlreicher Abbildungen eignet sich der Band hervorragend als einführendes Lehrbuch - und zwar nicht nur für Physik-Studenten, sondern auch für Studierende angrenzender Natur- und Ingenieurwissenschaften. Grundlegende Eigenschaften, supraleitende Elemente, Cooper-Paarung, Thermodynamik, kritische Ströme, Josephsonkontakte...

  10. Ausbildung und Erwartungshaltung (United States)

    Knoke, Holger


    werden Geologiestudenten zeitgemäß ausgebildet? Wird in der Angewandten Geologie das gelehrt, was in Wirtschaftsunternehmen an Wissen von einem Geologen erwartet wird? Erfolgt die spezielle Ausbildung zum Hydrogeologen fundiert und umfassend? Eine Antwort auf diese Fragen kann sicherlich nicht allumfassend gegeben werden, da sie von der jeweiligen Sichtweise abhängig ist. Ein Geologieprofessor wird die Ausbildung seiner Studenten im Großen und Ganzen als zeitgemäß einstufen, eventuell hier und da Verbesserungen für möglich halten. Auffällig ist die hohe Anzahl der in den letzten Jahren bereits geänderten oder zur Änderung anstehenden Studienordnungen. Es zeigt, daß die Straffung des Studiums sowie eine zumindest teilweise neue Wichtung der Schwerpunkte notwendig war bzw. ist, wobei im allgemeinen eine höhere Stundenzahl in den Grundlagenfächern Mathematik, Physik und Chemie angesetzt wird. Betrachtet man die Gesamtstundenzahlen der alten und der reformierten Studienordnungen, kann jedoch von einer Kürzung der Pflichtstunden in den meisten Fällen nicht die Rede sein. Eine grundlegende Reform des Geologiestudiums ist zur Zeit nicht zu erkennen, eher eine Verschulung des Studienganges. Die Entwicklung scheint zur Zeit weg von der freien Kurswahl und hin zu Modulangeboten mit vorgegebenen Kursen und Reihenfolgen zu gehen. Für die Hydrogeologie-Professoren ist es sicherlich nicht einfach zu entscheiden und in ihrem Kollegenkreis durchzusetzen, was aus dem generellen geowissenschaftlichen Kursangebot für einen Hydrogeologen notwendig oder aber entbehrlich ist. Genügen die Grundlagen der Paläontologie und der Mineralogie? Kann man ganz darauf verzichten? Was erwarten Behörden und Wirtschaftsunternehmen an allgemeinen und Spezialkenntnissen? Geologische Landesämter z. B. wollen, pauschal betrachtet, Geologen alten Stils. Ist ausdrücklich ein Angewandter Geologe oder speziell ein Hydrogeologe erwünscht, soll dieser die Spezialkenntnisse zus

  11. Nationale und transnationale Vernetzung polnischer Städte und Regionen: Auf dem Weg zu einer nachhaltigen Stadt- und Regionalentwicklung


    Dorsch, Pamela


    "Die Studie 'Nationale und transnationale Vernetzung polnischer Städte und Regionen - Bedeutung für eine nachhaltige Stadt- und Regionalentwicklung' liefert einen Überblick über die Einbindung polnischer Kommunen und Wojewodschaften in allgemeine und politikfeldspezifische Netzwerke auf nationaler und transnationaler Ebene. Besondere Berücksichtigung findet hierbei die Vernetzung in Fragen von Nachhaltigkeit und des Umweltschutzes. Einführend zeigt die Studie den Prozess zunehmender Dezentral...

  12. Patient-derived acute myeloid leukemia (AML) bone marrow cells display distinct intracellular kinase phosphorylation patterns

    International Nuclear Information System (INIS)

    Shults, Keith; Flye, Leanne; Green, Lisa; Daly, Thomas; Manro, Jason R; Lahn, Michael


    Multiparametric analyses of phospho-protein activation in patients with acute myeloid leukemia (AML) offers a quantitative measure to monitor the activity of novel intracellular kinase (IK) inhibitors. As recent clinical investigation with FMS-like tyrosine-3 inhibitors demonstrated, targeting IK with selective inhibitors can have a modest clinical benefit. Because multiple IKs are active in patients with AML, multikinase inhibitors may provide the necessary inhibition profile to achieve a more sustained clinical benefit. We here describe a method of assessing the activation of several IKs by flow cytometry. In 40 different samples of patients with AML we observed hyper-activated phospho-proteins at baseline, which is modestly increased by adding stem cell factor to AML cells. Finally, AML cells had a significantly different phospho-protein profile compared with cells of the lymphocyte gate. In conclusion, our method offers a way to determine the activation status of multiple kinases in AML and hence is a reliable assay to evaluate the pharmacodynamic activity of novel multikinase inhibitors

  13. Zwischen Freakout und Normcore

    Directory of Open Access Journals (Sweden)

    Beate Großegger


    Full Text Available Bis Ende des 20. Jahrhunderts war Rebellion jugendkulturell ein großes Thema. Heute hat die Jugend das so genannte Establishment aus den Augen verloren; die breite Mehrheit gibt sich postheroisch, setzt auf individualitätsbezogene Werte und träumt, eingeschlossen in ihre bunten Lifestyleblasen, von einem perfekten Leben. Bezugnehmend auf aktuelle Befunde der Jugend- und Generationenforschung gibt Beate Großegger in ihrem Beitrag einen Überblick über die wichtigsten Werte- und Lifestyletrends im frühen 21. Jahrhundert und zeigt dabei, wie sehr die heutige Jugend Kind ihrer Zeit und Produkt gesellschaftlicher Rahmenbedingungen ist. Until the late 20th century rebellion was an important aspect of various youth subcultures. But today’s youth has a different mindset. The majority acts post-heroically, i.e. they rather focus on their individual, their private lifestyle than opposing against the establishment. Wrapped in their lifestyle filterbubbles, they dream of a perfect life. Based on recent youth und generation studies Beate Großegger gives an overview of the most important youth cultural trends in the fields of values and lifestyles and introduces today’s youth as a child of our times.

  14. Neue Laser und Strahlquellen - alte und neue Risiken?

    DEFF Research Database (Denmark)

    Paasch, Uwe; Schwandt, Antje; Seeber, Nikolaus


    Die Entwicklungen im Bereich dermatologischer Laser, hochenergetischer Blitzlampen, LED und neuer Energie- und Strahlquellen der letzten Jahre haben gezeigt, dass mit neuen Wellenlängen, Konzepten und Kombinationen zusätzliche, zum Teil über den ästhetischen Bereich hinaus gehende therapeutische ...

  15. Führung und Machiavellismus

    NARCIS (Netherlands)

    Belschak, F.D.; den Hartog, D.N.; Felfe, J.


    In diesem Beitrag wird der Zusammenhang zwischen Führung und Machiavellismus aus zwei verschiedenen Perspektiven betrachtet. Zum einen werden neuere Forschungsergebnisse referiert, wie machiavellistische Mitarbeiter auf verschiedene Führungsstile ihres Vorgestzten reagieren und so mit Hinblick auf

  16. Netzformen und VDE-Bestimmungen (United States)

    Bernstein, Herbert

    Der Verband Deutscher Elektrotechniker (VDE) hat eine Reihe von Vorschriften ausgearbeitet, die dem Schutz von Leben und Sachen beim Umgang mit elektrischer Energie dienen. Besonders wichtig sind die in den VDE-Bestimmungen 0100 und 0411 festgelegten Vorschriften.

  17. Delegation und Kooperation im Gesundheitswesen


    Rosenau, Henning


    Delegation und Kooperation im Gesundheitswesen. - In: Tıpta işbirliği ve hukuksal sorunlar = Delegation und Kooperation im Gesundheitswesen / ed.: Hakan Hakeri ... - Samsun : Adalet, 2010. - S. 7-18

  18. Risiko Video- und Computerspiele? Eine Studie über Video- und Computerspielnutzung und Aggression bei 12- und 16- jährigen Jugendlichen


    Schiller, Eva-Maria; Strohmeier, Dagmar; Spiel, Christiane


    Video -und Computerspielen ist heutzutage eine beliebte Freizeitaktivität von Kindern und Jugendlichen, besonders von Jungen. Trotz der großen Vielfalt der angebotenen Video- und Computerspiele für Kinder und Jugendliche, konzentriert sich die Forschung vorwiegend auf negative Einflüsse von gewalthaltigen Video- und Computerspielen. Da nicht alle Kinder und Jugendliche ausschließlich gewalthaltige Video- und Computerspiele spielen, betrachten wir diesen Fokus in der Wissenschaft als zu eng ge...

  19. Expression Profiling of Ribosome Biogenesis Factors Reveals Nucleolin as a Novel Potential Marker to Predict Outcome in AML Patients.

    Directory of Open Access Journals (Sweden)

    Virginie Marcel

    Full Text Available Acute myeloid leukemia (AML is a heterogeneous disease. Prognosis is mainly influenced by patient age at diagnosis and cytogenetic alterations, two of the main factors currently used in AML patient risk stratification. However, additional criteria are required to improve the current risk classification and better adapt patient care. In neoplastic cells, ribosome biogenesis is increased to sustain the high proliferation rate and ribosome composition is altered to modulate specific gene expression driving tumorigenesis. Here, we investigated the usage of ribosome biogenesis factors as clinical markers in adult patients with AML. We showed that nucleoli, the nucleus compartments where ribosome production takes place, are modified in AML by analyzing a panel of AML and healthy donor cells using immunofluorescence staining. Using four AML series, including the TCGA dataset, altogether representing a total of about 270 samples, we showed that not all factors involved in ribosome biogenesis have clinical values although ribosome biogenesis is increased in AML. Interestingly, we identified the regulator of ribosome production nucleolin (NCL as over-expressed in AML blasts. Moreover, we found in two series that high NCL mRNA expression level was associated with a poor overall survival, particular in elderly patients. Multivariate analyses taking into account age and cytogenetic risk indicated that NCL expression in blast cells is an independent marker of reduced survival. Our study identifies NCL as a potential novel prognostic factor in AML. Altogether, our results suggest that the ribosome biogenesis pathway may be of interest as clinical markers in AML.

  20. c-Jun N-terminal kinase mediates AML1-ETO protein-induced connexin-43 expression

    International Nuclear Information System (INIS)

    Gao Fenghou; Wang Qiong; Wu Yingli; Li Xi; Zhao Kewen; Chen Guoqiang


    AML1-ETO fusion protein, a product of leukemia-related chromosomal translocation t(8;21), was reported to upregulate expression of connexin-43 (Cx43), a member of gap junction-constituted connexin family. However, its mechanism(s) remains unclear. By bioinformatic analysis, here we showed that there are two putative AML1-binding consensus sequences followed by two activated protein (AP)1 sites in the 5'-flanking region upstream to Cx43 gene. AML1-ETO could directly bind to these two AML1-binding sites in electrophoretic mobility shift assay, but luciferase reporter assay revealed that the AML1 binding sites were not indispensable for Cx43 induction by AML1-ETO protein. Conversely, AP1 sites exerted an important role in this event. In agreement, AML1-ETO overexpression in leukemic U937 cells activated c-Jun N-terminal kinase (JNK), while its specific inhibitor SP600125 effectively abrogated AML1-ETO-induced Cx43 expression, indicating that JNK signaling pathway contributes to AML1-ETO induced Cx43 expression. These results would shed new insights for understanding mechanisms of AML1-ETO-associated leukemogenesis

  1. An international consortium proposal of uniform response criteria for myelodysplastic/myeloproliferative neoplasms (MDS/MPN) in adults. (United States)

    Savona, Michael R; Malcovati, Luca; Komrokji, Rami; Tiu, Ramon V; Mughal, Tariq I; Orazi, Attilio; Kiladjian, Jean-Jacques; Padron, Eric; Solary, Eric; Tibes, Raoul; Itzykson, Raphael; Cazzola, Mario; Mesa, Ruben; Maciejewski, Jaroslaw; Fenaux, Pierre; Garcia-Manero, Guillermo; Gerds, Aaron; Sanz, Guillermo; Niemeyer, Charlotte M; Cervantes, Francisco; Germing, Ulrich; Cross, Nicholas C P; List, Alan F


    Myelodysplastic syndromes (MDS) and myeloproliferative neoplasms (MPN) are hematologically diverse stem cell malignancies sharing phenotypic features of both myelodysplastic syndromes and myeloproliferative neoplasms. There are currently no standard treatment recommendations for most adult patients with MDS/MPN. To optimize efforts to improve the management and disease outcomes, it is essential to identify meaningful clinical and biologic end points and standardized response criteria for clinical trials. The dual dysplastic and proliferative features in these stem cell malignancies define their uniqueness and challenges. We propose response assessment guidelines to harmonize future clinical trials with the principal objective of establishing suitable treatment algorithms. An international panel comprising laboratory and clinical experts in MDS/MPN was established involving 3 independent academic MDS/MPN workshops (March 2013, December 2013, and June 2014). These recommendations are the result of this collaborative project sponsored by the MDS Foundation. © 2015 by The American Society of Hematology.

  2. Mouse Drawer System (MDS): An autonomous hardware for supporting mice space research (United States)

    Liu, Y.; Biticchi, R.; Alberici, G.; Tenconi, C.; Cilli, M.; Fontana, V.; Cancedda, R.; Falcetti, G.


    For the scientific community the ability of flying mice under weightless conditions in space, compared to other rodents, offers many valuable advantages. These include the option of testing a wide range of wild-type and mutant animals, an increased animal number for flight, and a reduced demand on shuttle resources and crew time. In this study, we describe a spaceflight hardware for mice, the Mouse Drawer System (MDS). MDS can interface with Space Shuttle middeck and International Space Station Express Rack. It consists of Mice Chamber, Liquid Handling Subsystem, Food Delivery Subsystem, Air Conditioning Subsystem, Illumination Subsystem, Observation Subsystem and Payload Control Unit. It offers single or paired containment for 6-8 mice with a mean weight of 40 grams/mouse for a period of up to 3 months. Animal tests were conducted in a MDS breadboard to validate the biocompatibility of various subsystems. Mice survived in all tests of short and long duration. Results of blood parameters, histology and air/waste composition analysis showed that MDS subsystems meet the NIH guidelines for temperature, humidity, food and water access, air quality, odour and waste management.

  3. Ellbogen- und Handgelenksendoprothetik beim Rheumatiker - Richtlinien und Rehabilitation

    Directory of Open Access Journals (Sweden)

    Chochole M


    Full Text Available Die Endoprothetik an Ellbogen und Handgelenk ist seit etwa drei Jahrzehnten etabliert. An beiden Gelenken haben sich einzelne Implantate oder Designs durchgesetzt. Operationstechniken und Nachuntersuchungsergebnisse sind publiziert. Wenig ist jedoch zum Thema Nachbehandlung und Nachsorge veröffentlicht. Diese Arbeit beschäftigt sich detailliert mit der ärztlichen und therapeutischen Betreuung nach Implantation einer Ellbogen- oder Handgelenksendoprothese beim Patienten mit rheumatischer Arthritis unter Aufgliederung in Krankenhausaufenthalt, ambulanter Nachsorge sowie stationärer Rehabilitation. Dabei werden Zeitrahmen, Therapieziele und Behandlungen gesondert angeführt.

  4. Outcome of children with acute myeloid leukaemia (AML) experiencing primary induction failure in the AIEOP AML 2002/01 clinical trial. (United States)

    Quarello, Paola; Fagioli, Franca; Basso, Giuseppe; Putti, Maria C; Berger, Massimo; Luciani, Matteo; Rizzari, Carmelo; Menna, Giuseppe; Masetti, Riccardo; Locatelli, Franco


    Paediatric patients with acute myeloid leukaemia (AML) who fail induction due to primary resistance to chemotherapy account for a significant proportion of cases and have a particularly dismal prognosis. We report the clinical and biological data, and final outcome of 48 paediatric patients with primary-resistant AML enrolled in the Associazione Italiana di Ematologia e Oncologia Pediatrica AML 2002/01 clinical trial. These patients had a significantly higher white blood cell count at diagnosis compared to other AML patients. Cytogenetic and molecular features did not differ between patients with primary induction failure and patients allocated to the high-risk group. For the whole patient population, the probability of overall survival, event-free survival (EFS) and disease-free survival (DFS) was 21·8% ± 6·2, 20·4% ± 5·9, and 49·5% ± 11·3, respectively. Twenty-eight (58%) patients received haematopoietic stem cell transplantation (HSCT); 3 were autologous and 25 were allogeneic. Patients who underwent HSCT had improved EFS (31·2% vs. 5%, P < 0·0001). Only one of the 20 patients who did not receive HSCT is alive and disease free. The 19 patients in complete remission at time of HSCT showed significantly better DFS than the 9 with active disease (46% vs. 0%, P = 0·02). This study represents one of the largest series with long-term follow up of paediatric AML patients with primary refractory disease. Children who underwent transplantation had an encouraging long-term outcome. Disease recurrence remains the major cause of treatment failure; a better understanding of the disease biology is desirable to develop more effective treatment strategies. © 2015 John Wiley & Sons Ltd.

  5. Altautoverwertung zwischen Staat und Markt: Bedingungen und Potentiale zur Modernisierung von Lagerhaltung und Marketing gebrauchter Autoteile


    Lucas, Rainer


    Das Arbeitspapier diskutiert vor dem Hintergrund veränderter gesetzlicher Rahmen-und Wettbewerbsbedingungen in der Autoverwertung Ziele und Maßnahmen zurStärkung kleiner und mittelständischer Verwertungsbetriebe. Der Bereich GebrauchteAutoteile wird im Rahmen eines regionalen Fallbeispiels einer tiefergehenden Analyseunterzogen. Hieraus werden Vorschläge zur regionalen Netzwerkbildung innerhalb derBranche und neue Dienstleistungsperspektiven abgeleitet. Ein wesentliches Koope-rationsfeld ist ...

  6. Development of a Minimum Data Set (MDS) for C-Section Anesthesia Information Management System (AIMS). (United States)

    Sheykhotayefeh, Mostafa; Safdari, Reza; Ghazisaeedi, Marjan; Khademi, Seyed Hossein; Seyed Farajolah, Seyedeh Sedigheh; Maserat, Elham; Jebraeily, Mohamad; Torabi, Vahid


    Caesarean section, also known as C-section, is a very common procedure in the world. Minimum data set (MDS) is defined as a set of data elements holding information regarding a series of target entities to provide a basis for planning, management, and performance evaluation. MDS has found a great use in health care information systems. Also, it can be considered as a basis for medical information management and has shown a great potential for contributing to the provision of high quality care and disease control measures. The principal aim of this research was to determine MDS and required capabilities for Anesthesia information management system (AIMS) in C-section in Iran. Data items collected from several selected AIMS were studied to establish an initial set of data. The population of this study composed of 115 anesthesiologists was asked to review the proposed data elements and score them in order of importance by using a five-point Likert scale. The items scored as important or highly important by at least 75% of the experts were included in the final list of minimum data set. Overall 8 classes of data (consisted of 81 key data elements) were determined as final set. Also, the most important required capabilities were related to airway management and hypertension and hypotension management. In the development of information system (IS) based on MDS and identification, because of the broad involvement of users, IS capabilities must focus on the users' needs to form a successful system. Therefore, it is essential to assess MDS watchfully by considering the planned uses of data. Also, IS should have essential capabilities to meet the needs of its users.

  7. Valuation of transfusion-free living in MDS: results of health utility interviews with patients

    Directory of Open Access Journals (Sweden)

    Lübbert Michael


    Full Text Available Abstract Background This study measured how myelodysplastic syndrome (MDS patients value transfusion independence (TI, reduced transfusions (RT and transfusion-dependence (TD using health utility assessment methodology. Methods 47 MDS patients were interviewed, US (n = 8, France (n = 9, Germany (n = 9 and the UK (n = 21, to elicit the utility value of TI, RT and TD. Health states were developed based on literature; patient forum discussions; and were validated by a hematologist. Face-to-face interviews used the feeling thermometer Visual Analogue Scale (VAS and the Time Trade-Off (TTO method to value the health states on a 0 (dead to 1 (perfect health scale. Socio-demographic, clinical, and quality-of-life (EQ-5D characteristics were surveyed to describe the patient sample. Results and Discussion The mean age was 67 years (range: 29-83; 45% male, 70% retired; 40% had secondary/high school education, or higher (32%, and 79% lived with family, a partner or spouse, or friends. The mean time from MDS diagnosis was 5 years (range:1-23. Most patients (87% received previous transfusions and 49% had received a transfusion in the last 3 months. Mean EQ-5D index score was 0.78; patients reported at least some problem with mobility (45%, usual activities (40%, pain/discomfort (47%, and anxiety/depression (34%. Few patients had difficulty understanding the VAS (n = 3 and TTO (n = 4 exercises. Utility scores for TI were higher than for RT (0.84 vs. 0.77; p Conclusion Patients value TI, suggesting an important role for new treatments aiming to achieve greater TI in MDS. These results can be used in preference-based health economic evaluation of new MDS treatments, such as in future cost-utility studies.

  8. Rosetta und Yella

    Directory of Open Access Journals (Sweden)

    Urs Urban


    Full Text Available L’apparition de l’homo oeconomicus marque la fin des grands récits et par là de l’ensemble social que ceux-ci avaient légitimé. En même temps cependant il entre dans les récits littéraires – et filmiques, par exemple dans Rosetta (1999 des frères Dardenne et Yella (2007 de Christian Petzold. L’article se propose de montrer comment ces derniers réussissent à mettre en scène les apories existentielles d’un sujet produit par le dispositif économique en appliquant des procédés narratifs permettant de problématiser la narration elle-même.Mit dem Auftauchen des homo oeconomicus scheint das Ende der großen Erzählungen und des von diesen legitimierten sozialen Zusammenhangs besiegelt. Genau in diesem Moment indes beginnen sich die kleinen, die literarischen und filmischen Erzählformen für den ökonomischen Menschen zu interessieren. In dem Artikel geht es darum zu zeigen, wie die Brüder Dardenne und Christian Petzold die Aporien eines vom ökonomischen Dispositiv produzierten Subjekts in ihren Filmen Rosetta (1999 und Yella (2007 erzählerisch umsetzen und dabei genau diese erzählerische Umsetzbarkeit in Frage stellen.

  9. Supraleitung Grundlagen und Anwendungen

    CERN Document Server

    Buckel, Werner


    Grundlegende Konzepte und Eigenschaften von Supraleitern, die Herstellung und Entwicklung von neuen supraleitenden Materialien sowie moderne Anwendungsbereiche sind die Schwerpunktthemen des Buches. Das größte Potential zur Nutzung der Supraleitung liegt in der Energietechnik. Fast unbemerkt trägt die Einführung von Kabeln, Magneten, Transformatoren oder Lagern aus supraleitenden Materialien bei zur Effizienzsteigerung bei der Stromübertragung oder in Motoren. Durch seiner klare Sprache und zahlreiche erläuternde Abbildungen eignet sich der Band hervorragend als einführendes Lehrbuch. Der Schwierigkeitsgrad wird von Kapitel zu Kapitel gesteigert. So können auch Einsteiger ohne einschlägige Vorkenntnisse dem Stoff folgen. Dank der über 350 Literaturhinweise bekommt der Leser außerdem einen Überblick über die wichtigsten Publikationen zum Thema. Ein unverzichtbares Lehrbuch also für Physik-Studenten und Studierende der Ingenieurwissenschaften. Fachleuten in Forschung und Praxis leistet das Buch au...

  10. Der Nahostkonflikt und die Medien

    Directory of Open Access Journals (Sweden)

    Carola Richter


    Full Text Available Diese Einführung in eine Themenausgabe zu den vielfältigen Rollen der Medien im Nahostkonflikt skizziert die Probleme, die sich für Medien und Journalisten als Akteure im Konflikt, Adressaten der Konfliktparteien und Anlass für Konflikt durch ihre Berichterstattung ergeben. Das Konfliktgebiet Israel und Palästina ist sowohl für Forschung über Auslandsbericht-erstattung, über transnationale Agenda Building- und Public Diplomacy-Prozesse als auch über mediensystemische Entwicklungen in Besatzer- und Besatzungsgebieten interessant. Der Artikel gibt einen Überblick über das Feld und führt dabei in die in der Themenausgabe präsentierten empirischen Studien zum Nahostkonflikt und den Medien ein.

  11. The TPO/c-MPL pathway in the bone marrow may protect leukemia cells from chemotherapy in AML Patients. (United States)

    Dong-Feng, Zeng; Ting, Liu; Yong, Zhang; Cheng, Chang; Xi, Zhang; Pei-Yan, Kong


    Accumulating evidence indicates that the interaction of human LSCs (leukemic stem cells) with the hematopoietic microenvironment, mediated by the thrombopoietin (TPO)/c-MPL pathway, may be an underlying mechanism for resistance to cell cycle-dependent cytotoxic chemotherapy. However, the role of TPO/c-MPL signaling in AML (acute myelogenous leukemia) chemotherapy resistance hasn't been fully understood. The c-MPL and TPO levels in different AML samples were measured by flow cytometry and ELISA. We also assessed the TPO levels in the osteoblasts derived from bone mesenchymal stem cells (BMSCs). The survival rate of an AML cell line that had been co-cultured with different BMSC-derived osteoblasts was measured to determine the IC50 of an AML chemotherapy drug daunorubicin (DNR). The levels of TPO/c-MPL in the initial and relapse AML patients were significantly higher than that in the control (P MPL expression was found in the bone marrow mononuclear cells of the relapse AML patients. More importantly, the IC50 of DNR in the HEL + AML-derived osteoblasts was the highest among all co-culture systems. High level of TPO/c-MPL signaling may protect LSCs from chemotherapy in AML. The effects of inhibition of the TPO/c-MPL pathway on enhancing the chemotherapy sensitivity of AML cells, and on their downstream effector molecules that direct the interactions between patient-derived blasts and leukemia repopulating cells need to be further studied.

  12. Die biene und ihre produkte in der kunst und im alltagsleben (Fruhchristliche und byzantinische Zeit

    Directory of Open Access Journals (Sweden)

    Liveri Angeliki


    Full Text Available Die vorliegende Arbeit ist in zwei Teile geteilt: den kunst- und kulturhistorischen Teil. Im ersten Teil werden Darstellungen uber Bienen Bienenzucht, Honig und Wachs seit der fruhchristlichen bis zur spatbyzantinischen Zeit vorgefuhrt. Daher ist es als Beitrag in der "Ikonographie" der Biene wahrend dieser Zeit zu verstehen. Im kulturhistorischen Teil werden Informationen uber die Bienenzucht, den Handel mit Honig und Wachs sowie ihre vielfaltige Anwendung von der byzantinischen Gesellschaft an Hand der primaren Quellen, des Standes der Forschung und der archaologischen Funden erwahnt. Damit ist erwunscht ein moglichst gutes Bild der byzantinischen Bienenzucht wieder zu geben und die Nutzung der Bienenprodukte in Byzanz anschaulich zu machen.

  13. Digitalisierung und Selbstbestimmung

    Directory of Open Access Journals (Sweden)

    Eisenberger, Iris


    Full Text Available Kurztext: Der Beitrag beleuchtet das Verhältnis von Digitalisierung und Recht. Am Beispiel der Blockchain-Technologie wird aufgezeigt, wie neue Formen und Räume der Selbstbestimmung geschaffen werden können. In distribuierten Systemen ist die Tendenz erkennbar, dass sich die rechtliche hin zu einer technologischen Steuerung verlagert. Wenn Funktionen, die für gewöhnlich der demokratisch legitimierte Gesetzgeber wahrnimmt, auf andere Systeme übergehen, führt dies zu Herausforderungen für rechtsstaatliche Demokratien. Fundamentale Fragen von Kontrolle und Machtbeschränkung iZm Digitalisierung stehen im Fokus. Der Beitrag plädiert schließlich für „legal foresight“-Forschung im Bereich neuer Technologien.

  14. MDS shows a higher expression of hTERT and alternative splice variants in unactivated T-cells. (United States)

    Dong, Wen; Wu, Lei; Sun, Houfang; Ren, Xiubao; Epling-Burnette, Pearlie K; Yang, Lili


    Telomere instability and telomerase reactivation are believed to play an important role in the development of myelodysplastic syndromes (MDS). Abnormal enzymatic activity of human telomerase reverse transcriptase (hTERT), and its alternative splice variants have been reported to account for deregulated telomerase function in many cancers. In this study, we aim to compare the differences in expression of hTERT and hTERT splice variants, as well as telomere length and telomerase activity in unstimulated T-cells between MDS subgroups and healthy controls. Telomere length in MDS cases was significantly shorter than controls (n = 20, pMDS using World Health Organization classification (WHO subgroups versus control: RARS, p= 0.009; RCMD, p=0.0002; RAEB1/2, p=0.004, respectively) and the International Prognostic Scoring System (IPSS subgroups: Low+Int-1, pMDS patients (n=20) had significantly higher telomerase activity (p=0.002), higher total hTERT mRNA levels (p=0.001) and hTERT α+β- splice variant expression (pMDS (r=0.58, p=0.007). This data is in sharp contrast to data published previously by our group showing a reduction in telomerase and hTERT mRNA in MDS T-cells after activation. In conclusion, this study provides additional insight into hTERT transcript patterns and activity in peripheral T-cells of MDS patients. Additional studies are necessary to better understand the role of this pathway in MDS development and progression.

  15. Validity of the RAI-MDS for ascertaining diabetes and comorbid conditions in long-term care facility residents. (United States)

    Lix, Lisa M; Yan, Lin; Blackburn, David; Hu, Nianping; Schneider-Lindner, Verena; Teare, Gary F


    This study assessed the validity of the Resident Assessment Instrument Minimum Data Set (RAI-MDS) Version 2.0 for diagnoses of diabetes and comorbid conditions in residents of long-term care facilities (LTCFs). Hospital inpatient, outpatient physician billing, RAI-MDS, and population registry data for 1997 to 2011 from Saskatchewan, Canada were used to ascertain cases of diabetes and 12 comorbid conditions. Prevalence estimates were calculated for both RAI-MDS and administrative health data. Sensitivity, specificity, and positive and negative predictive values (PPV and NPV) were calculated using population-based administrative health data as the validation data source. Cohen's κ was used to estimate agreement between the two data sources. 23,217 LTCF residents were in the diabetes case ascertainment cohort. Diabetes prevalence was 25.3% in administrative health data and 21.9% in RAI-MDS data. Overall sensitivity of a RAI-MDS diabetes diagnoses was 0.79 (95% CI: 0.79, 0.80) and the PPV was 0.92 (95% CI: 0.91, 0.92), when compared to administrative health data. Sensitivity of the RAI-MDS for ascertaining comorbid conditions ranged from 0.21 for osteoporosis to 0.92 for multiple sclerosis; specificity was high for most conditions. RAI-MDS clinical assessment data are sensitive to ascertain diabetes cases in LTCF populations when compared to administrative health data. For many comorbid conditions, RAI-MDS data have low validity when compared to administrative data. Risk-adjustment measures based on these comorbidities might not produce consistent results for RAI-MDS and administrative health data, which could affect the conclusions of studies about health outcomes and quality of care across facilities.

  16. "Deutsche Kultur" und Werbung


    Schug, Alexander


    Die Arbeit präsentiert die Geschichte der modernen Wirtschaftswerbung in der ersten Hälfte des 20. Jahrhunderts und zeigt, dass Werbung trotz kultureller Barrieren die Alltagswelten der Deutschen kolonialisierte und Einfluss auf die „deutsche Kultur“ nahm. Die Arbeit zeigt, dass das Konstrukt der „deutschen Kultur“ nicht ausschließlich durch die bürgerliche Hochkultur definiert wurde, sondern zunehmend auch durch Einflüsse der Konsumkultur bestimmt war. Die Bilderwelten der Werbung prägten na...

  17. Work-Life-Balance und Frauenbiographien


    Macha, Hildegard


    Work-Life-Balance und Frauenbiographien. - In: Bildungs- und Karrierewege von Frauen / Anne Schlüter (Hrsg.). - Opladen : Budrich, 2006. - S. 17-32. - (Reihe: Frauen- und Geschlechterforschung in der Erziehungswissenschaft ; 2)

  18. Nutzerorientiertes Management von materiellen und immateriellen Informationsobjekten


    Hübsch, Chris


    Schaffung einer stabilen, erweiterbaren und skalierbaren Infrastruktur für die Bereitstellung von Diensten im Umfeld von Bibliotheken und ähnlichen wissensanbietenden Einrichtungen unter Verwendung von XML-RPC und Python.

  19. Das IHS und die Rolle der Forschungsinstitute


    Keuschnigg, Christian


    Das Institut für Höhere Studien und wissenschaftliche Forschung (IHS) ist ein unabhängiges Forschungsinstitut und leistet Forschung und Ausbildung auf Spitzenniveau für Politik, Wirtschaft und Gesellschaft. Im Wettbewerb zwischen Universitäten und angewandten Forschungsinstituten ist das IHS einzigartig, weil es unter einem Dach Grundlagenforschung und forschungsnahe Lehre mit angewandter Forschung für die wissenschaftliche Politikberatung verbindet. Mit den drei Disziplinen Ökonomie, Soziolo...

  20. Myeloid Sarcoma Predicts Superior Outcome in Pediatric AML; Can Cytogenetics Solve the Puzzle? (United States)

    Pramanik, Raja; Tyagi, Anudishi; Chopra, Anita; Kumar, Akash; Vishnubhatla, Sreenivas; Bakhshi, Sameer


    The purpose of our study was to evaluate the clinical, cytogenetic, and molecular features, and survival outcomes in patients with acute myeloid leukemia (AML) with myeloid sarcoma (MS) and compare them with patients with AML without MS. This was a retrospective analysis of de novo pediatric AML patients with or without MS diagnosed at our cancer center between June 2003 and June 2016. MS was present in 121 of 570 (21.2%), the most frequent site being the orbit. Patients with MS had a younger median age (6 years vs. 10 years) and presented with higher hemoglobin and platelet but lower white blood cell count compared with patients without MS. Further, t (8; 21) (P < .01), loss of Y chromosome (P < .01), and deletion 9q (P = .03) were significantly higher in patients with AML with MS. Event-free survival (EFS; P = .003) and overall survival (OS; P = .001) were better among patients with AML with MS (median EFS 21.0 months and median OS 37.1 months) compared with those with AML without MS (median EFS 11.2 months and median OS 16.2 months). The t (8; 21) was significantly associated with MS (odds ratio, 3.92). In a comparison of the 4 groups divided according to the presence or absence of MS and t (8; 21), the subgroup of patients having MS without concomitant t (8; 21) was the only group to have a significantly better OS (hazard ratio, 0.53; 95% confidence interval, 0.34-0.82; P = .005). Although t (8; 21) was more frequently associated with MS, it did not appear to be the reason for better outcome. Copyright © 2018 Elsevier Inc. All rights reserved.

  1. AML1/ETO trans-activates c-KIT expression through the long range interaction between promoter and intronic enhancer. (United States)

    Tian, Ying; Wang, Genjie; Hu, Qingzhu; Xiao, Xichun; Chen, Shuxia


    The AML1/ETO onco-fusion protein is crucial for the genesis of t(8;21) acute myeloid leukemia (AML) and is well documented as a transcriptional repressor through dominant-negative effect. However, little is known about the transactivation mechanism of AML1/ETO. Through large cohort of patient's expression level data analysis and a series of experimental validation, we report here that AML1/ETO transactivates c-KIT expression through directly binding to and mediating the long-range interaction between the promoter and intronic enhancer regions of c-KIT. Gene expression analyses verify that c-KIT expression is significantly high in t(8;21) AML. Further ChIP-seq analysis and motif scanning identify two regulatory regions located in the promoter and intronic enhancer region of c-KIT, respectively. Both regions are enriched by co-factors of AML1/ETO, such as AML1, CEBPe, c-Jun, and c-Fos. Further luciferase reporter assays show that AML1/ETO trans-activates c-KIT promoter activity through directly recognizing the AML1 motif and the co-existence of co-factors. The induction of c-KIT promoter activity is reinforced with the existence of intronic enhancer region. Furthermore, ChIP-3C-qPCR assays verify that AML1/ETO mediates the formation of DNA-looping between the c-KIT promoter and intronic enhancer region through the long-range interaction. Collectively, our data uncover a novel transcriptional activity mechanism of AML1/ETO and enrich our knowledge of the onco-fusion protein mediated transcription regulation. © 2017 Wiley Periodicals, Inc.

  2. Disease evolution and outcomes in familial AML with germline CEBPA mutations

    DEFF Research Database (Denmark)

    Tawana, Kiran; Wang, Jun; Renneville, Aline


    collected from 10 CEBPA-mutated families, representing 24 members with acute myeloid leukemia (AML). Whole-exome (WES) and deep sequencing were performed to genetically profile tumors and define patterns of clonal evolution. Germline CEBPA mutations clustered within the N-terminal and were highly penetrant......, with AML presenting at a median age of 24.5 years (range, 1.75-46 years). In all diagnostic tumors tested (n = 18), double CEBPA mutations (CEBPAdm) were detected, with acquired (somatic) mutations preferentially targeting the C-terminal. Somatic CEBPA mutations were unstable throughout the disease course...

  3. CD16xCD33 bispecific killer cell engager (BiKE) activates NK cells against primary MDS and MDSC CD33+ targets. (United States)

    Gleason, Michelle K; Ross, Julie A; Warlick, Erica D; Lund, Troy C; Verneris, Michael R; Wiernik, Andres; Spellman, Stephen; Haagenson, Michael D; Lenvik, Alexander J; Litzow, Mark R; Epling-Burnette, Pearlie K; Blazar, Bruce R; Weiner, Louis M; Weisdorf, Daniel J; Vallera, Daniel A; Miller, Jeffrey S


    Myelodysplastic syndromes (MDS) are stem cell disorders that can progress to acute myeloid leukemia. Although hematopoietic cell transplantation can be curative, additional therapies are needed for a disease that disproportionally afflicts the elderly. We tested the ability of a CD16xCD33 BiKE to induce natural killer (NK) cell function in 67 MDS patients. Compared with age-matched normal controls, CD7(+) lymphocytes, NK cells, and CD16 expression were markedly decreased in MDS patients. Despite this, reverse antibody-dependent cell-mediated cytotoxicity assays showed potent degranulation and cytokine production when resting MDS-NK cells were triggered with an agonistic CD16 monoclonal antibody. Blood and marrow MDS-NK cells treated with bispecific killer cell engager (BiKE) significantly enhanced degranulation and tumor necrosis factor-α and interferon-γ production against HL-60 and endogenous CD33(+) MDS targets. MDS patients had a significantly increased proportion of immunosuppressive CD33(+) myeloid-derived suppressor cells (MDSCs) that negatively correlated with MDS lymphocyte populations and CD16 loss on NK cells. Treatment with the CD16xCD33 BiKE successfully reversed MDSC immunosuppression of NK cells and induced MDSC target cell lysis. Lastly, the BiKE induced optimal MDS-NK cell function irrespective of disease stage. Our data suggest that the CD16xCD33 BiKE functions against both CD33(+) MDS and MDSC targets and may be therapeutically beneficial for MDS patients.

  4. Meta-Analytical Online Repository of Gene Expression Profiles of MDS Stem Cells (United States)


    lymphoid cell percentages in these samples. We observed that most of the MDS samples had lymphoid and neutrophil percentages that were in the normal...pathways involved in chemokine signaling, cytokine-cytokine receptor interaction, innate immunity signaling, hematopoietic cell lineage regulation, and...transcription factors are important for survival of cancer stem cells .2,34-36 IL8 is also an important regulator of innate immunity. Recent data have shown

  5. Diagrammatik und Wissensorganisation

    Directory of Open Access Journals (Sweden)

    Sascha Freyberg


    Full Text Available EinleitungDie Formen des „Sichtbarmachens“ in der Wissenschaft reichen von „Abbildungen“ über „Modelle“ bis hin zu „Simulationen“. Sie können u.a. gezeichnet, fotografiert, geometrisch konstruiert oder durch Sensorik vermittelt, digital prozessiert werden. Ihre Funktionen erstrecken sich von der Orientierung bis hin zur (hypothetischen Voraussage und somit auch vom Überblick bis zur Evidenzsuggestion. Generell handelt es sich um vereinfachte (und vereinfachende Darstellungen von (teilweise sehr komplexen Sachverhalten, zu deren Verständnis sie beitragen sollen; daher können sie bei Lernprozessen, d.h. in der Vermittlung und auch bei der Organisation von Wissen eine wichtige Rolle spielen. Diese kommt ihnen nun nicht nur zu, weil sie – wie in den mittelalterlichen Mnemotechniken – als Gedächtnisstützen für bekannte Sachverhalte dienen. Sondern resultiert auch aus ihrem Potenzial für die Entdeckung von neuen Zusammenhängen. Der folgende Artikel diskutiert die Darstellungsform des Diagramms. Es wird hier mit dem Gedanken gespielt, dass die in der universalen Zeichentheorie von C.S. Peirce entwickelte Diagrammatik wichtige Impulse für eine Untersuchung des Zusammenhangs von Wissen und Bildlichkeit geben kann.

  6. Arbeitsgestaltung und Mitarbeiterqualifizierung (United States)

    Weiss-Oberdorfer, Werner; Hörner, Barbara; Holm, Ruth; Pirner, Evelin

    Die Wertkette gliedert ein Unternehmen in strategisch relevante Tätigkeiten, um dadurch Kostenverhalten sowie vorhandene und potenzielle Differenzierungsquellen zu verstehen. Wenn ein Unternehmen diese strategisch wichtigen Aktivitäten billiger oder besser als seine Konkurrenten erledigt, verschafft es sich einen Wettbewerbsvorteil." Michael Porter, 1985

  7. Substanzbegriff und systematik

    NARCIS (Netherlands)

    Lütjeharms, W.J.


    Bei der Einteilung der Organismen, welche in dieser Arbeit mir von botanischem Gesichtspunkt betrachtet wird, ist die Frage nach „wesentlichen” Merkmalen oder Einteilungsgründen von grosser Wichtigkeit. Es ist die Frage nach der Substanz (Essenz) und den akzidentellen Merkmalen. Der Substanzbegriff

  8. Stenting und technische Stentumgebung (United States)

    Hoffstetter, Marc; Pfeifer, Stefan; Schratzenstaller, Thomas; Wintermantel, Erich

    In hoch entwickelten Industrieländern stehen laut Weltgesundheitsorganisation (WHO) Herz-Kreislauf-Erkrankungen und speziell die Koronare Herzkrankheit (KHK) an erster Stelle der Todesursachen. In Deutschland betrug die Zahl der erfassten, an KHK erkrankten Personen ohne Berücksichtigung der Dunkelziffer allein im Jahre 2001 über 473.000. Die KHK war im Jahre 2003 mit 92.673 erfassten Todesfällen immer noch die häufigste Todesursache, obgleich in Deutschland die Häufigkeit der Koronarinterventionen zur Behandlung der KHK zwischen 1984 und 2003 um fast das 80fache von 2.809 auf 221.867 Eingriffe pro Jahr gestiegen ist [1]. Neben der hohen Zahl an Todesfällen haben die betroffenen Personen durch chronische Schmerzen und eingeschränkte körperliche Leistungsfähigkeit zusätzlich eine starke Beeinträchtigung der Lebensqualität [2].In Folge dessen wird die erkrankte Person häufig zum Pflegefall was neben den gesundheitlichen Aspekten auch eine sozioökonomische Komponente in Form der fehlenden Arbeitskraft und den auftretenden Pflegekosten nach sich zieht. Die Kosten für die Behandlung der KHK in Deutschland beliefen sich im Jahre 2002 laut Statistischem Bundesamt auf rund 6,9 Mrd. €. Verglichen mit ähnlichen Zahlen der USA dürfte sich der entstandene Schaden für die deutsche Volkswirtschaft im zwei- bis dreistelligen Milliardenbereich bewegen [3].

  9. Phase I Trial of the Selective Inhibitor of Nuclear Export, KPT-330, in Relapsed Childhood ALL and AML (United States)


    Relapsed Acute Lymphoblastic Leukemia (ALL); Refractory Acute Lymphoblastic Leukemia (ALL); Relapsed Acute Myelogenous Leukemia (AML); Refractory Acute Myelogenous Leukemia (AML); Relapsed Mixed Lineage Leukemia; Refractory Mixed Lineage Leukemia; Relapsed Biphenotypic Leukemia; Refractory Biphenotypic Leukemia; Chronic Myelogenous Leukemia (CML) in Blast Crisis

  10. Herausforderungen kleiner und mittlerer Unternehmen (United States)

    Bergmann, Lars; Crespo, Isabel

    Vielfältige externe Herausforderungen, hervorgerufen durch die Dynamik, mit der sich die wirtschaftliche, technologische, soziokulturelle sowie politische Umwelt wandelt, muss jedes Unternehmen im Laufe der Zeit bestehen (Zäpfel 2000). Diese Herausforderungen werden heute insbesondere durch eine Globalisierung der Wettbewerbssowie Nachfragestrukturen verstärkt. Immer schnellere Prozessund Produktinnovationen, kürzere Produktlebenszyklen und Entwicklungszeiten, eine rasant steigende Variantenvielfalt, Nachfrageschwankungen sowie rasante Entwicklungen der Informations- und Kommunikationstechnologien sind einige der sich schnell verändernden Rahmenbedingungen. Zudem müssen sich Unternehmen an neue Gesetze und rechtliche Rahmenbedingungen anpassen. Im Bereich der Roh- und Einsatzstoffe sind Veränderungen insbesondere durch sich verknappende Rohstoffe und Primärenergieträger und in Folge dessen durch drastische Preissteigerungen für Materialien, Hilfsstoffe, Werkzeuge etc. geprägt.

  11. Limited clinical efficacy of azacitidine in transfusion-dependent, growth factor-resistant, low- and Int-1-risk MDS

    DEFF Research Database (Denmark)

    Holm, Mette; Dybedahl, I; Holm, Mette


    This prospective phase II study evaluated the efficacy of azacitidine (Aza)+erythropoietin (Epo) in transfusion-dependent patients with lower-risk myelodysplastic syndrome (MDS). Patients ineligible for or refractory to full-dose Epo+granulocyte colony stimulation factors for >8 weeks and a trans...... patients, but efficacy is limited, toxicity substantial and most responses of short duration. This treatment cannot be generally recommended in lower-risk MDS. Mutational screening revealed a high frequency of mutations....

  12. EVI and MDS/EVI are required for adult intestinal stem cell formation during postembryonic vertebrate development. (United States)

    Okada, Morihiro; Shi, Yun-Bo


    The gene ectopic viral integration site 1 (EVI) and its variant myelodysplastic syndrome 1 (MDS)/EVI encode zinc-finger proteins that have been recognized as important oncogenes in various types of cancer. In contrast to the established role of EVI and MDS/EVI in cancer development, their potential function during vertebrate postembryonic development, especially in organ-specific adult stem cells, is unclear. Amphibian metamorphosis is strikingly similar to postembryonic development around birth in mammals, with both processes taking place when plasma thyroid hormone (T3) levels are high. Using the T3-dependent metamorphosis in Xenopus tropicalis as a model, we show here that high levels of EVI and MDS/EVI are expressed in the intestine at the climax of metamorphosis and are induced by T3. By using the transcription activator-like effector nuclease gene editing technology, we have knocked out both EVI and MDS/EVI and have shown that EVI and MDS/EVI are not essential for embryogenesis and premetamorphosis in X. tropicalis On the other hand, knocking out EVI and MDS/EVI causes severe retardation in the growth and development of the tadpoles during metamorphosis and leads to tadpole lethality at the climax of metamorphosis. Furthermore, the homozygous-knockout animals have reduced adult intestinal epithelial stem cell proliferation at the end of metamorphosis (for the few that survive through metamorphosis) or during T3-induced metamorphosis. These findings reveal a novel role of EVI and/or MDS/EVI in regulating the formation and/or proliferation of adult intestinal adult stem cells during postembryonic development in vertebrates.-Okada, M., Shi, Y.-B. EVI and MDS/EVI are required for adult intestinal stem cell formation during postembryonic vertebrate development. © FASEB.

  13. The MDS-UPDRS Part II (motor experiences of daily living) resulted useful for assessment of disability in Parkinson's disease. (United States)

    Rodriguez-Blazquez, Carmen; Rojo-Abuin, Jose Manuel; Alvarez-Sanchez, Mario; Arakaki, Tomoko; Bergareche-Yarza, Alberto; Chade, Anabel; Garretto, Nelida; Gershanik, Oscar; Kurtis, Monica M; Martinez-Castrillo, Juan Carlos; Mendoza-Rodriguez, Amelia; Moore, Henry P; Rodriguez-Violante, Mayela; Singer, Carlos; Tilley, Barbara C; Huang, Jing; Stebbins, Glenn T; Goetz, Christopher G; Martinez-Martin, Pablo


    To evaluate the motor experiences of daily living section of the Movement Disorders Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS M-EDL) for assessing disability in PD patients; to determine the association between disability and quality of life; and to identify cut-off score ranges for no, mild, moderate and severe disability with this measure. International, observational, cross-sectional study of 435 PD patients, assessed with: MDS-UPDRS, Hoehn and Yahr staging, Rapid Assessment of Disability Scale, Clinical Impression of Severity Index for PD, Parkinson's Disease Questionnaire-8 and EQ-5D. Descriptive statistics, Spearman's rank correlation coefficients, Kruskal-Wallis test for group comparisons, ordinal logistic regression analysis for setting cut-off values and a step-wise multiple linear regression model were calculated. MDS-UPDRS M-EDL correlated 0.70-0.80 with other disability measures, and -0.46 to 0.74 with quality of life scales. Scores significantly increased with higher disease duration and severity (p MDS-UPDRS nM-EDL section as the main determinant of M-EDL, followed by the rest of MDS-UPDRS sections (explained variance: 59%). MDS-UPDRS M-EDL proved to be useful for assessing disability in PD. Copyright © 2013 Elsevier Ltd. All rights reserved.

  14. Th17 Cells Exhibit Antitumor Effects in MDS Possibly through Augmenting Functions of CD8+ T Cells. (United States)

    Li, Jing; Yue, Lanzhu; Wang, Huaquan; Liu, Chunyan; Liu, Hui; Tao, Jinglian; Qi, Weiwei; Wang, Yihao; Zhang, Wei; Fu, Rong; Shao, Zonghong


    Th17 cells are a newly found subset of distinct CD4+ Th effector cells' family and are found to play an important role in cancers. Myelodysplastic syndromes (MDS) are a common malignant hematological disease. Here, we showed that both the percentage and the function of Th17 cells were elevated in low-risk MDS while being decreased in high-risk MDS. Levels of upstream molecules of Th17 cells, IL-6 and IL-23, were higher in low-risk MDS but lower in high-risk MDS patients. The abnormal percentage of Th17 cells was closely related to clinical parameters including karyotype, morphologic blast percentage of bone marrow, peripheral absolute neutrophil count, and hemoglobin concentration. Furthermore, expression rates of perforin and granzyme B in BM CD3+CD8+ cells (cytotoxic T lymphocyte, CTL) positively correlated with levels of IL-17 but negatively correlated with BM blast percentage and could be significantly increased after stimulation with human recombinant IL-17 (rhIL-17). Our results suggested that Th17 cells might play an antitumor effect in the pathogenesis of MDS through IL-17/CTL pathway.

  15. KRAS (G12D Cooperates with AML1/ETO to Initiate a Mouse Model Mimicking Human Acute Myeloid Leukemia

    Directory of Open Access Journals (Sweden)

    Shanmin Zhao


    Full Text Available Background/Aims: It has been demonstrated that KRAS mutations represent about 90% of cancer-associated mutations, and that KRAS mutations play an essential role in neoplastic transformation. Cancer-associated RAS mutations occur frequently in acute myeloid leukemia (AML, suggesting a functional role for Ras in leukemogenesis. Methods: We successfully established a mouse model of human leukemia by transplanting bone marrow cells co-transfected with the K-ras (G12D mutation and AML1/ETO fusion protein. Results: Mice transplanted with AML/ETO+KRAS co-transduced cells had the highest mortality rate than mice transplanted with AML/ETO- or KRAS-transduced cells (115d vs. 150d. Upon reaching a terminal disease stage, EGFP-positive cells dominated their spleen, lymph nodes, peripheral blood and central nervous system tissue. Immunophenotyping, cytologic analyses revealed that AML/ETO+KRAS leukemias predominantly contained immature myeloid precursors (EGFP+/c-Kit+/Mac-1-/Gr-1-. Histologic analyses revealed that massive leukemic infiltrations were closely packed in dense sheets that effaced the normal architecture of spleen and thymus in mice transplanted with AML1/ETO + KRAS co-transduced cells. K-ras mRNA and protein expression were upregulated in bone marrow cells of the K-ras group and AML1/ETO + Kras group. The phosphorylation of MEK/ERK was significantly enhanced in the AML1/ETO + Kras group. The similar results of the AML1/ETO + Nras group were consistent with those reported previously. Conclusion: Co-transduction of KrasG12D and AML1/ETO induces acute monoblastic leukemia. Since expression of mutant K-ras alone was insufficient to induce leukemia, this model may be useful for investigating the multi-step leukemogenesis model of human leukemia.

  16. The TAK1-NF-κB axis as therapeutic target for AML

    NARCIS (Netherlands)

    Bosman, Matthieu Cornelis Johannes; Schepers, Hein; Jaques, Jennifer; Vos, Annet; Quax, Wim Johannes; Schuringa, Jan Jacob; Vellenga, Edo


    Development and maintenance of leukemia can partially be attributed to alterations in (anti) apoptotic gene expression. Genome-wide transcriptome analyses revealed that 89 apoptosis-associated genes were differentially expressed between patient acute myeloid leukemia (AML) CD34(+) cells and normal

  17. Acute erythremic myelosis (true erythroleukaemia): a variant of AML FAB-M6. (United States)

    Hasserjian, R P; Howard, J; Wood, A; Henry, K; Bain, B


    Classic erythroleukaemia (acute myeloid leukaemia M6, or M6 AML) is defined as an excess of myeloblasts in an erythroid predominant background. Leukaemia variants in which the primitive blast cells are demonstrably erythroid are extremely rare and poorly characterised. Variably referred to as "true erythroleukaemia" or "acute erythremic myelosis", they are often included within the M6 AML category even though they do not meet strict criteria for this type of AML. Two cases of acute erythroid neoplasia are presented with clinical, morphological, immunophenotypic, and cytogenetic analysis. Both patients presented with profound anaemia, one in a setting of long standing myelodysplasia. Bone marrow examination revealed a predominant population of highly dysplastic erythroid cells in both cases. In one case, the liver was infiltrated by neoplastic erythroid cells. Both patients died within four months of diagnosis. This report illustrates that cases of acute leukaemia occur in which the dominant neoplastic cell is a primitive erythroid cell without an accompanying increase in myeloblasts. This does not preclude the neoplastic clone originating in a multipotent haemopoietic stem cell, as suggested by cases arising in patients with myelodysplasia. Acute erythremic myelosis should be recognised as a distinct variant of M6 AML.

  18. Genetic and epigenetic similarities and differences between childhood and adult AML

    DEFF Research Database (Denmark)

    Juhl-Christensen, Caroline; Ommen, Hans Beier; Aggerholm, Anni


    The biology of acute myeloid leukemia (AML) is complex and includes both genetic and epigenetic aberrations. We addressed the combined consequences of promoter hypermethylation of p15, CDH1, ER, MDR1, and RARB2 and mutation of NPM1, CEBPA, FLT3, and WT1 in a Danish cohort of 70 pediatric and 383...

  19. Zosuquidar restores drug sensitivity in P-glycoprotein expressing acute myeloid leukemia (AML)

    International Nuclear Information System (INIS)

    Tang, Ruoping; Faussat, Anne-Marie; Perrot, Jean-Yves; Marjanovic, Zora; Cohen, Simy; Storme, Thomas; Morjani, Hamid; Legrand, Ollivier; Marie, Jean-Pierre


    Chemotherapeutic drug efflux via the P-glycoprotein (P-gp) transporter encoded by the MDR1/ABCB1 gene is a significant cause of drug resistance in numerous malignancies, including acute leukemias, especially in older patients with acute myeloid leukemia (AML). Therefore, the P-gp modulators that block P-gp-mediated drug efflux have been developed, and used in combination with standard chemotherapy. In this paper, the capacity of zosuquidar, a specific P-gp modulator, to reverse chemoresistance was examined in both leukemia cell lines and primary AML blasts. The transporter protein expressions were analyzed by flow cytometry using their specific antibodies. The protein functionalities were assessed by the uptake of their fluorescence substrates in presence or absence their specific modulators. The drug cytotoxicity was evaluated by MTT test. Zosuquidar completely or partially restored drug sensitivity in all P-gp-expressing leukemia cell lines tested and enhanced the cytotoxicity of anthracyclines (daunorubicin, idarubicin, mitoxantrone) and gemtuzumab ozogamicin (Mylotarg) in primary AML blasts with active P-gp. In addition, P-gp inhibition by zosuquidar was found to be more potent than cyclosporine A in cells with highly active P-gp. These in vitro studies suggest that zosuquidar may be an effective adjunct to cytotoxic chemotherapy for AML patients whose blasts express P-gp, especially for older patients

  20. Prognostic Value of RUNX1 Mutations in AML: A Meta-Analysis (United States)

    Jalili, Mahdi; Yaghmaie, Marjan; Ahmadvand, Mohammad; Alimoghaddam, Kamran; Mousavi, Seyed Asadollah; Vaezi, Mohammad; Ghavamzadeh, Ardeshir


    The RUNX1 (AML1) gene is a relatively infrequent mutational target in cases of acute myeloid leukemia (AML). Previous work indicated that RUNX1 mutations can have pathological and prognostic implications. To evaluate prognostic value, we conducted a meta-analysis of 4 previous published works with data for survival according to RUNX1 mutation status. Pooled hazard ratios for overall survival and disease-free survival were 1.55 (95% confidence interval (CI) = 1.11–2.15; p-value = 0.01) and 1.76 (95% CI = 1.24–2.52; p-value = 0.002), respectively, for cases positive for RUNX1 mutations. This evidence supports clinical implications of RUNX1 mutations in the development and progression of AML cases and points to the possibility of a distinct category within the newer WHO classification. Though it must be kept in mind that the present work was based on data extracted from observational studies, the findings suggest that the RUNX1 status can contribute to risk-stratification and decision-making in management of AML. Creative Commons Attribution License

  1. Sorption und Verbreitung per- und polyfluorierter Chemikalien (PFAS) in Wasser und Boden


    Gellrich, Vanessa


    PFAS (= Perfluoroalkyl and Polyfluoroalkyl Substances) sind persistente organische Spurenstoffe, die weltweit in verschiedenen Umweltkompartimenten nachgewiesen werden konnten. Im Rahmen dieser Dissertation sollte die Frage geklärt werden, wie die physikalisch-chemischen Eigenschaften der PFAS - besonders ihre Sorption am Boden - ihr Verhalten und ihre Verbreitung in der Umwelt beeinflussen. Dazu wurde zunächst eine Messmethode entwickelt, optimiert und validiert, mit der 17 per- und polyf...

  2. A pilot study on the usefulness of peripheral blood flow cytometry for the diagnosis of lower risk myelodysplastic syndromes: the "MDS thermometer". (United States)

    Aires, Ana; Teixeira, Maria Dos Anjos; Lau, Catarina; Moreira, Cláudia; Spínola, Ana; Mota, Alexandra; Freitas, Inês; Coutinho, Jorge; Lima, Margarida


    Immunophenotypic analysis of the bone marrow (BM) cells has proven to be helpful in the diagnosis of Myelodysplastic Syndromes (MDS). However, the usefulness of flow cytometry (FCM) for the detection of myelodysplasia in the peripheral blood (PB) still needs to be investigated. The aim of this pilot study was to evaluate the value of FCM-based PB neutrophil and monocyte immunophenotyping for the diagnosis of lower risk MDS (LR-MDS). We evaluated by 8-color FCM the expression of multiple cell surface molecules (CD10, CD11b, CD11c, CD13, CD14, CD15, CD16, CD34, CD45, CD56, CD64 and HLA-DR) in PB neutrophils and monocytes from a series of 14 adult LR-MDS patients versus 14 normal individuals. Peripheral blood neutrophils from patients with LR-MDS frequently had low forward scatter (FSC) and side scatter (SSC) values and low levels of CD11b, CD11c, CD10, CD16, CD13 and CD45 expression, in that order, as compared to normal neutrophils. In addition, patients with LR-MDS commonly display a higher fraction of CD14 + CD56 + and a lower fraction of CD14 + CD16 + monocytes in the PB. Based on these results, we proposed an immunophenotyping score based on which PB samples from patients with LR-MDS could be distinguished from normal PB samples with a sensitivity 93% and a specificity of 100%. In addition, we used this score to construct the MDS Thermometer, a screening tool for detection and monitoring of MDS in the PB in clinical practice. Peripheral blood neutrophil and monocyte immunophenotyping provide useful information for the diagnosis of LR-MDS, as a complement to cytomorphology. If validated by subsequent studies in larger series of MDS patients and extended to non-MDS patients with cytopenias, our findings may improve the diagnostic assessment and avoid invasive procedures in selected groups of MDS patients.

  3. Peptide microarray profiling identifies phospholipase C gamma 1 (PLC-γ1) as a potential target for t(8;21) AML

    NARCIS (Netherlands)

    Mahmud, Hasan; Scherpen, Frank J. G.; Meeuwsen de Boer, Tiny; Lourens, Harm-Jan; Schoenherr, Caroline; Eder, Matthias; Scherr, Michaela; Guryev, Victor; de Bont, Eveline S.


    The t(8;21) (q22;q22) chromosomal translocation is one of the most frequent genetic alterations in acute myeloid leukemia (AML) which has a need for improved therapeutic strategies. We found PLC-γ1 as one of the highest phosphorylated peptides in t(8;21) AML samples compared to NBM or CN-AML in our

  4. Plazentaanatomie und -physiologie mit uteroplazentarem Kreislauf

    NARCIS (Netherlands)

    Engel, N.; Schreiber, J. U.; Kranke, Peter


    Die Plazenta besteht neben der Nabelschnur aus parenchymatösem Gewebe, der sog. Eihaut (Amnion) und der Zottenhaut (Chorion). Sie fungiert als Schnittstelle zwischen Mutter und Fetus und ermöglicht den physiologischen Transfer von Gasen, Nährstoffen und Metaboliten. Die Funktion der Plazenta ist als

  5. Hegel und Gorgias

    DEFF Research Database (Denmark)

    Huggler, Jørgen

    Hegel und Gorgias /Jørgen Huggler (University of Aarhus, Denmark) (huggler(at) Hegels Verständnis des Sophist Gorgias von Leontinoi in den Vorlesungen über die Geschichte der Philosophie gründet auf seine eigene Interpretation der Eleaten, insbesondere Zenon. Aufgrund eigener philosophischer...... „Gründen“, einen echten Beitrag zu dieser Entwicklung des griechischen Denkens geliefert. Vor allen scheint Gorgias die dialektischen Bemühungen der Eleaten fortgesetzt zu haben. Hegels Auslegung des Gorgias kann den lauwarmen Empfang der Sophisten in den deutschen Beiträgen zur Geschichte der Philosophie...... des späten 18. Jahrhunderts (Meiners, Tiedemann, Stäudlin, Buhle und Tennemann) gegenübergestellt werden. In der Tat ist Hegels philosophisches Verständnis ausreichend, um positive Kommentare zu allen Teilen der Diskussion in Gorgias Argument „Über das Nicht-Seiende, oder Über der Natur“ zu geben...

  6. Rudolf Streinz. Meinungs- und Informationsfreiheit zwischen Ost und West / Henn-Jüri Uibopuu

    Index Scriptorium Estoniae

    Uibopuu, Henn-Jüri, 1929-2012


    Tutvustus: Streinz, Rudolf. Meinungs- und Informationsfreiheit zwischen Ost und West : Möglichkeiten und Grenzen intersystemarer völkerrechtlicher Garantien in einem systemkonstituierenden Bereich. Ebelsbach : Rolf Gremer, 1981

  7. Zur historischen Aufarbeitung und medialen Vermittlung der Shoah in Italien und Deutschland

    Directory of Open Access Journals (Sweden)

    Peter Kuon


    Full Text Available Claudia Müller, Patrick Ostermann und Karl-Siegbert Rehberg, Hrsg., Die Shoah in Geschichte und Erinnerung: Perspektiven medialer Vermittlung in Italien und Deutschland (Bielefeld: transcript, 2015.

  8. Ethik und Sicherheitstechnik. Eine Handreichung

    NARCIS (Netherlands)

    Ammicht-Quinn, Regina; Nagenborg, Michael Herbert; Rampp, Benjamin; Wolkenstein, Andreas F.X.; Ammicht-Quinn, Regina


    Mit dem Programm „Forschung für die zivile Sicherheit“ fördert die Bundesregierung im Rahmen der „Hightech-Strategie für Deutschland“ erstmals unmittelbar die Entwicklung von Techniken, die der Schaffung und Bewahrung von ziviler Sicherheit dienen. Bei der Erforschung und Entwicklung von

  9. Relationship between the MDS-UPDRS and Quality of Life: A large multicenter study of 3206 patients. (United States)

    Skorvanek, Matej; Martinez-Martin, Pablo; Kovacs, Norbert; Zezula, Ivan; Rodriguez-Violante, Mayela; Corvol, Jean-Christophe; Taba, Pille; Seppi, Klaus; Levin, Oleg; Schrag, Anette; Aviles-Olmos, Iciar; Alvarez-Sanchez, Mario; Arakaki, Tomoko; Aschermann, Zsuzsanna; Benchetrit, Eve; Benoit, Charline; Bergareche-Yarza, Alberto; Cervantes-Arriaga, Amin; Chade, Anabel; Cormier, Florence; Datieva, Veronika; Gallagher, David A; Garretto, Nelida; Gdovinova, Zuzana; Gershanik, Oscar; Grofik, Milan; Han, Vladimir; Kadastik-Eerme, Liis; Kurtis, Monica M; Mangone, Graziella; Martinez-Castrillo, Juan Carlos; Mendoza-Rodriguez, Amelia; Minar, Michal; Moore, Henry P; Muldmaa, Mari; Mueller, Christoph; Pinter, Bernadette; Poewe, Werner; Rallmann, Karin; Reiter, Eva; Rodriguez-Blazquez, Carmen; Singer, Carlos; Valkovic, Peter; Goetz, Christopher G; Stebbins, Glenn T


    The relationship between Health-Related Quality of Life (HRQoL) and MDS-UPDRS has not been fully studied so far. The aim of this study was to evaluate the relationship between all MDS-UPDRS components and HRQoL in a representative international cohort of PD patients. We collected demographic and disease-related data as well as MDS-UPDRS and PDQ8 scales. Data were analyzed using correlations between PDQ8 and all MDS-UPDRS items, subsequently two hierarchical multiple regressions were performed, first between the scores of the MDS-UPDRS Parts and PDQ8 and second between individual items from those Parts demonstrating significant relationship to PDQ8 scores in the first regression. LASSO regression analyses were performed to evaluate the relationship between PDQ8 and all individual MDS-UPDRS items. A total of 3206 PD patients were included in the study. In the first regression analysis, PDQ8 was significantly related to MDS-UPDRS parts I and II, but not to III and IV. In the second regression model, significant contributions to PDQ8 were found for Part I items Fatigue, Pain, Depressed mood, Apathy; and Part II items Dressing, Doing hobbies, Freezing, Speech and Tremor. In the LASSO analysis, six Part I, seven Part II, three Part III and one Part IV items contributed to PDQ8 scores. The five items most significantly related to the model were Depressed mood, Dressing, Apathy, Pain and Fatigue. This is so far the largest study related to HRQoL issues in PD. Restrictions in activities of daily living and non-motor symptoms significantly contribute to HRQoL in PD. Copyright © 2018. Published by Elsevier Ltd.

  10. Relationship between the MDS-UPDRS domains and the health-related quality of life of Parkinson's disease patients. (United States)

    Martínez-Martín, P; Rodríguez-Blázquez, C; Forjaz, M J; Alvarez-Sánchez, M; Arakaki, T; Bergareche-Yarza, A; Chade, A; Garretto, N; Gershanik, O; Kurtis, M M; Martínez-Castrillo, J C; Mendoza-Rodríguez, A; Moore, H P; Rodríguez-Violante, M; Singer, C; Tilley, B C; Huang, J; Stebbins, G T; Goetz, C G


    The Movement Disorder Society sponsored version of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) is a comprehensive instrument for assessing Parkinson's disease (PD). The present study was aimed at determining the relationships between MDS-UPDRS components and health-related quality of life (HRQoL) evaluations in PD patients. An international, multicenter, cross-sectional study was carried out of 435 PD patients assessed with the MDS-UPDRS, Hoehn and Yahr (HY), Clinical Impression Severity for PD, EQ-5D and PD Questionnaire - eight items (PDQ-8). Spearman's rank correlation coefficients, exploratory factor analysis and multiple linear regression models (dependent variables EQ-5D and PDQ-8) were performed. The participants' age was 66.71 ± 10.32 years (51.5% men). PD duration was 8.52 ± 6.14, and median HY was 2 (range 1-5). The correlation between the EQ-5D index and the MDS-UPDRS ranged from -0.46 (Part IV) to -0.72 (Part II) and for the PDQ-8 index from 0.47 (Part III) to 0.74 (Part II). In multiple regression models with the MDS-UPDRS domains as independent variables, the main determinant for both the EQ-5D index and the PDQ-8 was Part II followed by Part I. After factorial grouping of the cardinal PD manifestations embedded in the MDS-UPDRS Parts III and IV for inclusion into multiple regression models, a factor formed by M-EDL, nM-EDL and fluctuations was the main determinant for both the EQ-5D and PDQ-8 indexes. The MDS-UPDRS component most tightly related with the HRQoL measures was a combination of motor and non-motor experiences of daily living. © 2014 The Author(s) European Journal of Neurology © 2014 EFNS.

  11. Comparison of clinical outcomes and prognostic utility of risk stratification tools in patients with therapy-related vs de novo myelodysplastic syndromes: a report on behalf of the MDS Clinical Research Consortium. (United States)

    Zeidan, A M; Al Ali, N; Barnard, J; Padron, E; Lancet, J E; Sekeres, M A; Steensma, D P; DeZern, A; Roboz, G; Jabbour, E; Garcia-Manero, G; List, A; Komrokji, R


    While therapy-related (t)-myelodysplastic syndromes (MDS) have worse outcomes than de novo MDS (d-MDS), some t-MDS patients have an indolent course. Most MDS prognostic models excluded t-MDS patients during development. The performances of the International Prognostic Scoring System (IPSS), revised IPSS (IPSS-R), MD Anderson Global Prognostic System (MPSS), WHO Prognostic Scoring System (WPSS) and t-MDS Prognostic System (TPSS) were compared among patients with t-MDS. Akaike information criteria (AIC) assessed the relative goodness of fit of the models. We identified 370 t-MDS patients (19%) among 1950 MDS patients. Prior therapy included chemotherapy alone (48%), chemoradiation (31%), and radiation alone in 21%. Median survival for t-MDS patients was significantly shorter than for d-MDS (19 vs 46 months, PMDS (PMDS had a significantly higher hazard of death relative to d-MDS in every risk model, and had inferior survival compared to patients with d-MDS within all risk group categories. AIC Scores (lower is better) were 2316 (MPSS), 2343 (TPSS), 2343 (IPSS-R), 2361 (WPSS) and 2364 (IPSS). In conclusion, subsets of t-MDS patients with varying clinical outcomes can be identified using conventional risk stratification models. The MPSS, TPSS and IPSS-R provide the best predictive power.

  12. Bildanalyse in Medizin und Biologie (United States)

    Athelogou, Maria; Schönmeyer, Ralf; Schmidt, Günther; Schäpe, Arno; Baatz, Martin; Binnig, Gerd

    Heutzutage sind bildgebende Verfahren aus medizinischen Untersuchungen nicht mehr wegzudenken. Diverse Methoden - basierend auf dem Einsatz von Ultraschallwellen, Röntgenstrahlung, Magnetfeldern oder Lichtstrahlen - werden dabei spezifisch eingesetzt und liefern umfangreiches Datenmaterial über den Körper und sein Inneres. Anhand von Mikroskopieaufnahmen aus Biopsien können darüber hinaus Daten über die morphologische Eigenschaften von Körpergeweben gewonnen werden. Aus der Analyse all dieser unterschiedlichen Arten von Informationen und unter Konsultation weiterer klinischer Untersuchungen aus diversen medizinischen Disziplinen kann unter Berücksichtigung von Anamnesedaten ein "Gesamtbild“ des Gesundheitszustands eines Patienten erstellt werden. Durch die Flut der erzeugten Bilddaten kommt der Bildverarbeitung im Allgemeinen und der Bildanalyse im Besonderen eine immer wichtigere Rolle zu. Gerade im Bereich der Diagnoseunterstützung, der Therapieplanung und der bildgeführten Chirurgie bilden sie Schlüsseltechnologien, die den Forschritt nicht nur auf diesen Gebieten maßgeblich vorantreiben.

  13. Overall survival in lower IPSS risk MDS by receipt of iron chelation therapy, adjusting for patient-related factors and measuring from time of first red blood cell transfusion dependence: an MDS-CAN analysis. (United States)

    Leitch, Heather A; Parmar, Ambica; Wells, Richard A; Chodirker, Lisa; Zhu, Nancy; Nevill, Thomas J; Yee, Karen W L; Leber, Brian; Keating, Mary-Margaret; Sabloff, Mitchell; St Hilaire, Eve; Kumar, Rajat; Delage, Robert; Geddes, Michelle; Storring, John M; Kew, Andrea; Shamy, April; Elemary, Mohamed; Lenis, Martha; Mamedov, Alexandre; Ivo, Jessica; Francis, Janika; Zhang, Liying; Buckstein, Rena


    Analyses suggest iron overload in red blood cell (RBC) transfusion-dependent (TD) patients with myleodysplastic syndrome (MDS) portends inferior overall survival (OS) that is attenuated by iron chelation therapy (ICT) but may be biassed by unbalanced patient-related factors. The Canadian MDS Registry prospectively measures frailty, comorbidity and disability. We analysed OS by receipt of ICT, adjusting for these patient-related factors. TD International Prognostic Scoring System (IPSS) low and intermediate-1 risk MDS, at RBC TD, were included. Predictive factors for OS were determined. A matched pair analysis considering age, revised IPSS, TD severity, time from MDS diagnosis to TD, and receipt of disease-modifying agents was conducted. Of 239 patients, 83 received ICT; frailty, comorbidity and disability did not differ from non-ICT patients. Median OS from TD was superior in ICT patients (5·2 vs. 2·1 years; P MDS, adjusting for age, frailty, comorbidity, disability, revised IPSS, TD severity, time to TD and receiving disease-modifying agents. This provides additional evidence that ICT may confer clinical benefit. © 2017 John Wiley & Sons Ltd.

  14. [Die baltischen Lande im Zeitalter der Reformation und Konfessionalisierung. Livland, Estland, Ösel, Ingermanland, Kurland und Letgallen. Stadt, Land und Konfession 1500-1721. 2. und 3. Teil] / Anti Selart

    Index Scriptorium Estoniae

    Selart, Anti, 1973-


    Arvustus: Die baltischen Lande im Zeitalter der Reformation und Konfessionalisierung. Livland, Estland, Ösel, Ingermanland, Kurland und Letgallen. Stadt, Land und Konfession 1500-1721. Hrsg. von Matthias Asche, Werner Buchholz, Anton Schindling. 2. und 3. Teil.

  15. The DVB Channel Coding Application Using the DSP Development Board MDS TM-13 IREF

    Directory of Open Access Journals (Sweden)

    M. Slanina


    Full Text Available The paper deals with the implementation of the channel codingaccording to DVB standard on DSP development board MDS TM-13 IREF andPC. The board is based on Philips Nexperia media processor andintegrates hardware video ADC and DAC. The program libraries featuresused for MPEG based video compression are outlined and then thealgorithms of channel decoding (FEC protection against errors arepresented including the flowchart diagrams. The paper presents thepartial hardware implementation of the simulation system that coversselected phenomena of DVB baseband processing and it is used for realtime interactive demonstration of error protection influence ontransmitted digital video in laboratory and education.

  16. Proliferative status of primitive hematopoietic progenitors from patients with acute myelogenous leukemia (AML). (United States)

    Guan, Y; Hogge, D E


    One possible explanation for the competitive advantage that malignant cells in patients with acute myelogenous leukemia (AML) appear to have over normal hematopoietic elements is that leukemic progenitors proliferate more rapidly than their normal progenitor cell counterparts. To test this hypothesis, an overnight 3H-thymidine (3H-Tdr) suicide assay was used to analyze the proliferative status of malignant progenitors detected in both colony-forming cell (CFC) and long-term culture initiating cell (LTC-IC) assays from the peripheral blood of nine patients with newly diagnosed AML. Culture of AML cells in serum-free medium with 100 ng/ml Steel factor (SF), 20 ng/ml interleukin 3 (IL-3) and 20 ng/ml granulocyte colony-stimulating factor (G-CSF) for 16-24 h maintained the number of AML-CFC and LTC-IC at near input values (mean % input +/- s.d. for CFC and LTC-IC were 78 +/- 33 and 126 +/- 53, respectively). The addition of 20 muCi/ml high specific activity 3H-Tdr to these cultures reduced the numbers of both progenitor cell types from most of the patient samples substantially: mean % kill +/- s.d. for AML-CFC and LTC-IC were 64 +/- 27 and 82 +/- 16, respectively, indicating that a large proportion of both progenitor populations were actively cycling. FISH analysis of colonies from CFC and LTC-IC assays confirmed that most cytogenetically abnormal CFC and LTC-IC were actively cycling (mean % kill +/- s.d.: 68 +/- 26 and 85 +/- 13, respectively). Interestingly, in six patient samples where a significant number of cytogenetically normal LTC-ICs were detected, the % kill of these cells (74 +/- 20) was similar to that of the abnormal progenitors. These data contrast with the predominantly quiescent cell cycle status of CFC and LTC-IC previously observed in steady-state peripheral blood from normal individuals but also provide evidence that a significant proportion of primitive malignant progenitors from AML patients are quiescent and therefore may be resistant to standard

  17. [Detection of heterogeneity and evolution of subclones in t(8;21) AML by QM-FISH]. (United States)

    Wang, Ying-chan; Hu, Lin-ping; Lin, Dong; Li, Cheng-wen; Yuan, Tian; Jia, Yu-jiao; Tian, Zheng; Tang, Ke-jing; Wang, Min; Wang, Jian-xiang


    To explore the heterogeneous subclones in acute myeloid leukemia (AML) with t(8;21) by quantitative multicolor- fluorescence in situ hybridization (QM-FISH), and to figure out whether there is putative ancestral relationship among different subclones. Bacterial artificial chromosomes (BAC) clones that contain the targeted genes including AML1, ETO, WT1, p27 and c-kit were searched in the data base UCSC Genome Bioinformatics. Multicolor FISH probes were prepared by linking fluorescein labeled dUTP or dCTP to targeted genes by nick translation. Bone marrow mononuclear cells from t (8;21) AML patients are dropped on to the wet surface of glass slides after hypotonic treatment and fixation. After hybridization, the fluorescence signals were captured by Zeiss fluorescence microscope. The copy number of AML1, ETO, WT1, p27, c- kit and the AML1-ETO fusion gene in AML1-ETO positive cells was counted. The cells with same signals were defined as a subclone. Various subclones were recorded and their proportions were calculated, and their evolutionary relationship was deduced. The subclones in matched primary and relapsed samples were compared, the evolution of dominant clones were figured out and the genomic abnormality that is associated with relapse and drug resistance were speculated. In this study, 36 primary AML with t(8;21) cases and 1 relapsed case paired with the primary case were detected. In these 36 primary cases, 4 cases (11.1%) acquired additional AML1-ETO fusion signal, 3(8.3%) had additional AML1 signal, 4(11.1%) had additional ETO signal, 20(55.6%) had additional WT1 signal, 15(41.7%) had additional p27 signal and 14(38.9%) had additional c-kit signal. In addition, 10(27.8%) displayed AML1 signal deletion, and such an aberration represents statistic significance in male patients. It seems that male patients usually accompany AML1 signal deletion. Of 36 cases, 28(77.8 %) harbored at least 2 subclones (ranged from 2 to 10). According to the genetic signature of

  18. Classification of Multiple Chinese Liquors by Means of a QCM-based E-Nose and MDS-SVM Classifier. (United States)

    Li, Qiang; Gu, Yu; Jia, Jing


    Chinese liquors are internationally well-known fermentative alcoholic beverages. They have unique flavors attributable to the use of various bacteria and fungi, raw materials, and production processes. Developing a novel, rapid, and reliable method to identify multiple Chinese liquors is of positive significance. This paper presents a pattern recognition system for classifying ten brands of Chinese liquors based on multidimensional scaling (MDS) and support vector machine (SVM) algorithms in a quartz crystal microbalance (QCM)-based electronic nose (e-nose) we designed. We evaluated the comprehensive performance of the MDS-SVM classifier that predicted all ten brands of Chinese liquors individually. The prediction accuracy (98.3%) showed superior performance of the MDS-SVM classifier over the back-propagation artificial neural network (BP-ANN) classifier (93.3%) and moving average-linear discriminant analysis (MA-LDA) classifier (87.6%). The MDS-SVM classifier has reasonable reliability, good fitting and prediction (generalization) performance in classification of the Chinese liquors. Taking both application of the e-nose and validation of the MDS-SVM classifier into account, we have thus created a useful method for the classification of multiple Chinese liquors.

  19. Classification of Multiple Chinese Liquors by Means of a QCM-based E-Nose and MDS-SVM Classifier

    Directory of Open Access Journals (Sweden)

    Qiang Li


    Full Text Available Chinese liquors are internationally well-known fermentative alcoholic beverages. They have unique flavors attributable to the use of various bacteria and fungi, raw materials, and production processes. Developing a novel, rapid, and reliable method to identify multiple Chinese liquors is of positive significance. This paper presents a pattern recognition system for classifying ten brands of Chinese liquors based on multidimensional scaling (MDS and support vector machine (SVM algorithms in a quartz crystal microbalance (QCM-based electronic nose (e-nose we designed. We evaluated the comprehensive performance of the MDS-SVM classifier that predicted all ten brands of Chinese liquors individually. The prediction accuracy (98.3% showed superior performance of the MDS-SVM classifier over the back-propagation artificial neural network (BP-ANN classifier (93.3% and moving average-linear discriminant analysis (MA-LDA classifier (87.6%. The MDS-SVM classifier has reasonable reliability, good fitting and prediction (generalization performance in classification of the Chinese liquors. Taking both application of the e-nose and validation of the MDS-SVM classifier into account, we have thus created a useful method for the classification of multiple Chinese liquors.

  20. TP53 suppression promotes erythropoiesis in del(5q) MDS, suggesting a targeted therapeutic strategy in lenalidomide-resistant patients (United States)

    Caceres, Gisela; McGraw, Kathy; Yip, Bon Ham; Pellagatti, Andrea; Johnson, Joseph; Zhang, Ling; Liu, Kenian; Zhang, Lan Min; Fulp, William J.; Lee, Ji-Hyun; Al Ali, Najla H.; Basiorka, Ashley; Smith, Larry J.; Daugherty, F. Joseph; Littleton, Neil; Wells, Richard A.; Sokol, Lubomir; Wei, Sheng; Komrokji, Rami S.; Boultwood, Jacqueline; List, Alan F.


    Stabilization of p53 in erythroid precursors in response to nucleosomal stress underlies the hypoplastic anemia in myelodysplastic syndromes (MDS) with chromosome 5q deletion [del(5q)]. We investigated whether cenersen, a clinically active 20-mer antisense oligonucleotide complementary to TP53 exon10, could suppress p53 expression and restore erythropoiesis in del(5q) MDS. Cenersen treatment of ribosomal protein S-14-deficient erythroblasts significantly reduced cellular p53 and p53-up-regulated modulator of apoptosis expression compared with controls, accompanied by a significant reduction in apoptosis and increased cell proliferation. In a two-stage erythroid differentiation assay, cenersen significantly suppressed nuclear p53 in bone marrow CD34+ cells isolated from patients with del(5q) MDS, whereas erythroid burst recovery increased proportionally to the magnitude of p53 suppression without evidence of del(5q) clonal suppression (r = −0.6; P = 0.005). To explore the effect of p53 suppression on erythropoiesis in vivo, dexamethasone, a glucocorticoid receptor-dependent p53 antagonist, was added to lenalidomide treatment in eight lower-risk, transfusion-dependent, del(5q) MDS patients with acquired drug resistance. Transfusion independence was restored in five patients accompanied by expansion of erythroid precursors and decreased cellular p53 expression. We conclude that targeted suppression of p53 could support effective erythropoiesis in lenalidomide-resistant del(5q) MDS. PMID:24043769

  1. Results of allogeneic stem cell transplantation in the Spanish MDS registry: prognostic factors for low risk patients. (United States)

    Díez Campelo, M; Sánchez-Barba, M; de Soria, V Gómez-García; Martino, R; Sanz, G; Insunza, A; Bernal, T; Duarte, R; Amigo, M L; Xicoy, B; Tormo, M; Iniesta, F; Bailén, A; Benlloch, L; Córdoba, I; López-Villar, O; Del Cañizo, M C


    Although new agents have been approved for the treatment of MDS, the only curative approach is allogeneic hematopoietic stem cell transplantation (HSCT) and thus, in particular circumstances this procedure has been proposed as a treatment option for low risk patients. We have retrospectively analyzed the results of HSCT in 291 patients from the Spanish MDS registry with special attention to low risk MDS (LR-MDS) in order to define the variables that could impact their clinical evolution after transplantation. At 2 years OS was 51% and EFS was 50% (95% CI 0.7-4.5 years for OS and 95% CI 0.1-3.9 years for EFS). Among 43 LR-MDS, transplant-related mortality was 28%. At 3 years, OS was 67% (95% CI 264.7-8927.2 days for OS) and EFS was 64% (95% CI 0-9697.2 days for EFS). In the multivariate analysis only cytogenetics retained statistical significant effect on both OS (p=.047) and EFS (p=.046). Conditioning regimen could improve outcome among this subset of patients (OS 86% and RFS 100% for patients receiving RIC regimen). The present study confirms that specific disease characteristic as well as transplant characteristics have a significant impact on transplant outcome. Regarding low risk patients a non-myeloablative conditioning would be preferable especially in cases without high-risk cytogenetics. Copyright © 2014 Elsevier Ltd. All rights reserved.

  2. Tissue-Specific Upregulation of MDS/EVI Gene Transcripts in the Intestine by Thyroid Hormone during Xenopus Metamorphosis (United States)

    Hasebe, Takashi; Fu, Liezhen; Heimeier, Rachel A.; Das, Biswajit; Ishizuya-Oka, Atsuko; Shi, Yun-Bo


    Background Intestinal remodeling during amphibian metamorphosis resembles the maturation of the adult intestine during mammalian postembryonic development when the adult epithelial self-renewing system is established under the influence of high concentrations of plasma thyroid hormone (T3). This process involves de novo formation and subsequent proliferation and differentiation of the adult stem cells. Methodology/Principal Findings The T3-dependence of the formation of adult intestinal stem cell during Xenopus laevis metamorphosis offers a unique opportunity to identify genes likely important for adult organ-specific stem cell development. We have cloned and characterized the ectopic viral integration site 1 (EVI) and its variant myelodysplastic syndrome 1 (MDS)/EVI generated via transcription from the upstream MDS promoter and alternative splicing. EVI and MDS/EVI have been implicated in a number of cancers including breast, leukemia, ovarian, and intestinal cancers. We show that EVI and MDS/EVI transcripts are upregulated by T3 in the epithelium but not the rest of the intestine in Xenopus laevis when adult stem cells are forming in the epithelium. Conclusions/Significance Our results suggest that EVI and MDS/EVI are likely involved in the development and/or proliferation of newly forming adult intestinal epithelial cells. PMID:23383234

  3. Genome-wide analysis of histone H3 acetylation patterns in AML identifies PRDX2 as an epigenetically silenced tumor suppressor gene

    DEFF Research Database (Denmark)

    Agrawal-Singh, Shuchi; Isken, Fabienne; Agelopoulos, Konstantin


    to have lower H3Ac levels in AML compared with progenitor cells, which suggested that a large number of genes are epigenetically silenced in AML. Intriguingly, we identified peroxiredoxin 2 (PRDX2) as a novel potential tumor suppressor gene in AML. H3Ac was decreased at the PRDX2 gene promoter in AML......With the use of ChIP on microarray assays in primary leukemia samples, we report that acute myeloid leukemia (AML) blasts exhibit significant alterations in histone H3 acetylation (H3Ac) levels at > 1000 genomic loci compared with CD34+ progenitor cells. Importantly, core promoter regions tended......, which correlated with low mRNA and protein expression. We also observed DNA hypermethylation at the PRDX2 promoter in AML. Low protein expression of the antioxidant PRDX2 gene was clinically associated with poor prognosis in patients with AML. Functionally, PRDX2 acted as inhibitor of myeloid cell...

  4. Diagnosis and management of AML in adults: 2017 ELN recommendations from an international expert panel. (United States)

    Döhner, Hartmut; Estey, Elihu; Grimwade, David; Amadori, Sergio; Appelbaum, Frederick R; Büchner, Thomas; Dombret, Hervé; Ebert, Benjamin L; Fenaux, Pierre; Larson, Richard A; Levine, Ross L; Lo-Coco, Francesco; Naoe, Tomoki; Niederwieser, Dietger; Ossenkoppele, Gert J; Sanz, Miguel; Sierra, Jorge; Tallman, Martin S; Tien, Hwei-Fang; Wei, Andrew H; Löwenberg, Bob; Bloomfield, Clara D


    The first edition of the European LeukemiaNet (ELN) recommendations for diagnosis and management of acute myeloid leukemia (AML) in adults, published in 2010, has found broad acceptance by physicians and investigators caring for patients with AML. Recent advances, for example, in the discovery of the genomic landscape of the disease, in the development of assays for genetic testing and for detecting minimal residual disease (MRD), as well as in the development of novel antileukemic agents, prompted an international panel to provide updated evidence- and expert opinion-based recommendations. The recommendations include a revised version of the ELN genetic categories, a proposal for a response category based on MRD status, and criteria for progressive disease. © 2017 by The American Society of Hematology.

  5. Synthese und Charakterisierung wasserfreier Seltenerdmetall-Nitrate, -Acetate und -Oxyacetate


    Heinrichs, Christina


    Durch thermische Entwässerung der Seltenerdmetall(SE)-Nitrat-Hydrate und der SE-Acetat-Hydrate im Argon-Strom/Vakuum konnten wasserfreie SE-Nitrate und SE-Nitrat-Monohydrate bzw. wasserfreie SE-Acetate erhalten werden. Es gelang zudem, SE-Oxyacetate durch thermische Zersetzung der SE-Acetate darzustellen. Des Weiteren wurde beim Erhitzen von Praseodym-Carbonat-Hydrat ein Pr-Carbonat-Hydroxid erhalten. Die Verbindungen wurden mittels Röntgenpulverdiffraktometrie und an ausgewählten Beispielen ...

  6. High frequency of streptococcal bacteraemia during childhood AML therapy irrespective of dose of cytarabine

    DEFF Research Database (Denmark)

    Johannsen, Katrine Helle; Handrup, Mette Møller; Lausen, Birgitte Frederiksen


    of cytarabine and more chemotherapy series (n = 6) than other protocols with the potential increased risk of severe VGS infections. PROCEDURE: Medical records of all Danish children enrolled on the NOPHO-AML-2004 protocol between January 2004 and September 2011 (n = 45) were retrospectively reviewed and all...... rate of VGS seemed independent of high-dose cytarabine but was more likely caused by the intensive chemotherapy treatment leading to severe mucositis and neutropenia....

  7. Socioeconomic status (SES) and childhood acute myeloid leukemia (AML) mortality risk: Analysis of SEER data. (United States)

    Knoble, Naomi B; Alderfer, Melissa A; Hossain, Md Jobayer


    Socioeconomic status (SES) is a complex construct of multiple indicators, known to impact cancer outcomes, but has not been adequately examined among pediatric AML patients. This study aimed to identify the patterns of co-occurrence of multiple community-level SES indicators and to explore associations between various patterns of these indicators and pediatric AML mortality risk. A nationally representative US sample of 3651 pediatric AML patients, aged 0-19 years at diagnosis was drawn from 17 Surveillance, Epidemiology, and End Results (SEER) database registries created between 1973 and 2012. Factor analysis, cluster analysis, stratified univariable and multivariable Cox proportional hazards models were used. Four SES factors accounting for 87% of the variance in SES indicators were identified: F1) economic/educational disadvantage, less immigration; F2) immigration-related features (foreign-born, language-isolation, crowding), less mobility; F3) housing instability; and, F4) absence of moving. F1 and F3 showed elevated risk of mortality, adjusted hazards ratios (aHR) (95% CI): 1.07(1.02-1.12) and 1.05(1.00-1.10), respectively. Seven SES-defined cluster groups were identified. Cluster 1 (low economic/educational disadvantage, few immigration-related features, and residential-stability) showed the minimum risk of mortality. Compared to Cluster 1, Cluster 3 (high economic/educational disadvantage, high-mobility) and Cluster 6 (moderately-high economic/educational disadvantages, housing-instability and immigration-related features) exhibited substantially greater risk of mortality, aHR(95% CI)=1.19(1.0-1.4) and 1.23 (1.1-1.5), respectively. Factors of correlated SES-indicators and their pattern-based groups demonstrated differential risks in the pediatric AML mortality indicating the need of special public-health attention in areas with economic-educational disadvantages, housing-instability and immigration-related features. Copyright © 2016 Elsevier Ltd. All

  8. Wormhole Detection Based on Ordinal MDS Using RTT in Wireless Sensor Network

    Directory of Open Access Journals (Sweden)

    Saswati Mukherjee


    Full Text Available In wireless communication, wormhole attack is a crucial threat that deteriorates the normal functionality of the network. Invasion of wormholes destroys the network topology completely. However, most of the existing solutions require special hardware or synchronized clock or long processing time to defend against long path wormhole attacks. In this work, we propose a wormhole detection method using range-based topology comparison that exploits the local neighbourhood subgraph. The Round Trip Time (RTT for each node pair is gathered to generate neighbour information. Then, the network is reconstructed by ordinal Multidimensional Scaling (MDS followed by a suspicion phase that enlists the suspected wormholes based on the spatial reconstruction. Iterative computation of MDS helps to visualize the topology changes and can localize the potential wormholes. Finally, a verification phase is used to remove falsely accused nodes and identify real adversaries. The novelty of our algorithm is that it can detect both short path and long path wormhole links. Extensive simulations are executed to demonstrate the efficacy of our approach compared to existing ones.

  9. Problems getting from the laboratory to the field: Reclamation of an AML site

    International Nuclear Information System (INIS)

    Dick, W.A.; Stehouwer, R.C.


    Acid and toxic abandoned mineland sites provide an opportunity whereby flue gas desulfurization (FGD) by-product can be beneficially used as a reclamation amendment material. Studies are needed to compare the effectiveness of FGD by-product, as compared with resoil, for reclamation purposes. Initial studies provided information about the chemical and physical properties of the FGD by-product and how to transport and blend the FGD by-product with yard waste compost. Greenhouse studies indicated that rates of 125 dry tons/acre of FGD and 50 dry tons/acre of yard waste compost would provide optimum results for reclamation of acid and toxic spoil contained at the Fleming abandoned mineland (AML) site. Their results showed that heavy metal loading rates were much lower using the FGD/compost mixture than using resoil material. Dioxin in the mixture was also less than the 5 ppt level considered as normal background. The technical problems of using FGD by-product for reclamation of an AML site were solved. However, considerable efforts to educate the public about the merits of reclaiming the Fleming AML site using this FGD/compost mixture were required before initiating field reclamation activities. Education efforts must continue if FGD by-products are to achieve general acceptance as a reclamation alternative to resoil in cases where resoil is of scarce supply

  10. A multigene array for measurable residual disease detection in AML patients undergoing SCT (United States)

    Goswami, M; McGowan, K S; Lu, K; Jain, N; Candia, J; Hensel, N F; Tang, J; Calvo, K R; Battiwalla, M; Barrett, A J; Hourigan, C S


    AML is a diagnosis encompassing a diverse group of myeloid malignancies. Heterogeneous genetic etiology, together with the potential for oligoclonality within the individual patient, have made the identification of a single high-sensitivity marker of disease burden challenging. We developed a multiple gene measurable residual disease (MG-MRD) RQ–PCR array for the high-sensitivity detection of AML, retrospectively tested on 74 patients who underwent allo-SCT at the NHLBI in the period 1994–2012. MG-MRD testing on peripheral blood samples prior to transplantation demonstrated excellent concordance with traditional BM-based evaluation and improved risk stratification for post-transplant relapse and OS outcomes. Pre-SCT assessment by MG-MRD predicted all clinical relapses occurring in the first 100 days after allo-SCT compared with 57% sensitivity using WT1 RQ–PCR alone. Nine patients who were negative for WT1 prior to transplantation were correctly reclassified into a high-risk MG-MRD-positive group, associated with 100% post-transplant mortality. This study provides proof of principle that a multiple gene approach may be superior to the use of WT1 expression alone for AML residual disease detection. PMID:25665046

  11. Editorial: Informationstechnische Bildung und Medienerziehung

    Directory of Open Access Journals (Sweden)

    Annemarie Hauf-Tulodziecki


    Full Text Available Die schulische Medienerziehung bzw. die Medienbildung hat ihre derzeit hohe öffentliche Aufmerksamkeit nicht zuletzt der Tatsache zu verdanken, dass gerade die so genannten «Neuen Medien» - heute oft mit den Schlagworten «Multimedia» oder «Internet» abgekürzt - wichtige Erziehungs- und Bildungsmassnahmen erforderlich machen. In der öffentlichen Diskussion gehören inhaltliche Kurzschlüsse zur Tagesordnung: Wenn von «Medienkompetenz» die Rede ist, verbirgt sich dahinter häufig nur ein «Internetführerschein». Diese Beobachtung ärgert nicht nur Medienpädagogen, sondern auch Vertreter einer Informationstechnischen Bildung (1, da berechtigte pädagogische Ansprüche beider Gruppen wenig Beachtung finden. Mittlerweile gibt es eine Reihe von Empfehlungen von BLK und KMK zu diesem Thema, in denen zudem deutlich auf die wechselseitigen Bezüge hingewiesen werden. Die wachsende Bedeutung des Mediums Computer und die weiter zunehmende Digitalisierung traditioneller Medien erfordert sowohl für die Medienerziehung als auch für die Informatische Bildung eine Weiterentwicklung ihrer Ziele und Inhalte. Die Gesellschaft für Informatik e.V. hat 1999 in ihrer Empfehlung «Informatische Bildung und Medienerziehung» aus ihrer Perspektive dargestellt, welche Aufgaben auf die Medienerziehung zukommen, wenn auch die Informations- und Kommunikationstechnologien bzw. die computerbasierten Medien in einer angemessenen Form thematisiert werden sollen. Erste praktische Ansätze, Inhalte aus beiden Bereichen bewusst zusammenzuführen, auch unter einer gemeinsamen Fach- oder Kursbezeichnung, sind häufig additiv und orientieren sich – trotz vorhandener Überschneidungen – an den etablierten medienpädagogischen oder an den informatischen Unterrichtsprinzipien. In dem vorliegenden Themenheft wird aus einer übergeordneten, medienpädagogischen Perspektive die Frage gestellt, wie eine konsistente Weiterentwicklung der Medienerziehung unter angemessener

  12. Role of casein kinase 1A1 in the biology and targeted therapy of del(5q) MDS (United States)

    Schneider, Rebekka K.; Ademà, Vera; Heckl, Dirk; Järås, Marcus; Mallo, Mar; Lord, Allegra M.; Chu, Lisa P.; McConkey, Marie E.; Kramann, Rafael; Mullally, Ann; Bejar, Rafael; Solé, Francesc; Ebert, Benjamin L.


    Summary The Casein kinase 1A1 gene (CSNK1A1) is a putative tumor suppressor gene located in the common deleted region for del(5q) myelodysplastic syndrome (MDS). We generated a murine model with conditional inactivation of Csnk1a1 and found that Csnk1a1 haploinsufficiency induces hematopoietic stem cell expansion and a competitive repopulation advantage whereas homozygous deletion induces hematopoietic stem cell failure. Based on this finding, we found that heterozygous inactivation of Csnk1a1 sensitizes cells to a CSNK1 inhibitor relative to cells with two intact alleles. In addition, we identified recurrent somatic mutations in CSNK1A1 on the non-deleted allele of patients with del(5q) MDS. These studies demonstrate that CSNK1A1 plays a central role in the biology of del(5q) MDS and is a promising therapeutic target. PMID:25242043


    Directory of Open Access Journals (Sweden)



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  14. Expanded and independent validation of the Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS). (United States)

    Martinez-Martin, Pablo; Rodriguez-Blazquez, Carmen; Alvarez-Sanchez, Mario; Arakaki, Tomoko; Bergareche-Yarza, Alberto; Chade, Anabel; Garretto, Nelida; Gershanik, Oscar; Kurtis, Monica M; Martinez-Castrillo, Juan Carlos; Mendoza-Rodriguez, Amelia; Moore, Henry P; Rodriguez-Violante, Mayela; Singer, Carlos; Tilley, Barbara C; Huang, Jing; Stebbins, Glenn T; Goetz, Christopher G


    The Movement Disorder Society-UPDRS (MDS-UPDRS) was published in 2008, showing satisfactory clinimetric results and has been proposed as the official benchmark scale for Parkinson's disease. The present study, based on the official MDS-UPDRS Spanish version, performed the first independent testing of the scale and adds information on its clinimetric properties. The cross-culturally adapted MDS-UPDRS Spanish version showed a comparative fit index ≥ 0.90 for each part (I-IV) relative to the English-language version and was accepted as the Official MDS-UPDRS Spanish version. Data from this scale, applied with other assessments to Spanish-speaking Parkinson's disease patients in five countries, were analyzed for an independent and complementary clinimetric evaluation. In total, 435 patients were included. Missing data were negligible and moderate floor effect (30 %) was found for Part IV. Cronbach's α index ranged between 0.79 and 0.93 and only five items did not reach the 0.30 threshold value of item-total correlation. Test-retest reliability was adequate with only two sub-scores of the item 3.17, Rest tremor amplitude, reaching κ values lower than 0.60. The intraclass correlation coefficient was higher than 0.85 for the total score of each part. Correlation of the MDS-UPDRS parts with other measures for related constructs was high (≥ 0.60) and the standard error of measurement lower than one-third baseline standard deviation for all subscales. Results confirm those of the original study and add information on scale reliability, construct validity, and precision. The MDS-UPDRS Spanish version shows satisfactory clinimetric characteristics.

  15. Caspase-3 controls AML1-ETO-driven leukemogenesis via autophagy modulation in a ULK1-dependent manner. (United States)

    Man, Na; Tan, Yurong; Sun, Xiao-Jian; Liu, Fan; Cheng, Guoyan; Greenblatt, Sarah M; Martinez, Camilo; Karl, Daniel L; Ando, Koji; Sun, Ming; Hou, Dan; Chen, Bingyi; Xu, Mingjiang; Yang, Feng-Chun; Chen, Zhu; Chen, Saijuan; Nimer, Stephen D; Wang, Lan


    AML1-ETO (AE), a fusion oncoprotein generated by t(8;21), can trigger acute myeloid leukemia (AML) in collaboration with mutations including c-Kit, ASXL1/2, FLT3, N-RAS, and K-RAS. Caspase-3, a key executor among its family, plays multiple roles in cellular processes, including hematopoietic development and leukemia progression. Caspase-3 was revealed to directly cleave AE in vitro, suggesting that AE may accumulate in a Caspase-3-compromised background and thereby accelerate leukemogenesis. Therefore, we developed a Caspase-3 knockout genetic mouse model of AML and found that loss of Caspase-3 actually delayed AML1-ETO9a (AE9a)-driven leukemogenesis, indicating that Caspase-3 may play distinct roles in the initiation and/or progression of AML. We report here that loss of Caspase-3 triggers a conserved, adaptive mechanism, namely autophagy (or macroautophagy), which acts to limit AE9a-driven leukemia. Furthermore, we identify ULK1 as a novel substrate of Caspase-3 and show that upregulation of ULK1 drives autophagy initiation in leukemia cells and that inhibition of ULK1 can rescue the phenotype induced by Caspase-3 deletion in vitro and in vivo. Collectively, these data highlight Caspase-3 as an important regulator of autophagy in AML and demonstrate that the balance and selectivity between its substrates can dictate the pace of disease. © 2017 by The American Society of Hematology.

  16. Proteasome inhibition enhances the efficacy of volasertib-induced mitotic arrest in AML in vitro and prolongs survival in vivo. (United States)

    Schnerch, Dominik; Schüler, Julia; Follo, Marie; Felthaus, Julia; Wider, Dagmar; Klingner, Kathrin; Greil, Christine; Duyster, Justus; Engelhardt, Monika; Wäsch, Ralph


    Elderly and frail patients, diagnosed with acute myeloid leukemia (AML) and ineligible to undergo intensive treatment, have a dismal prognosis. The small molecule inhibitor volasertib induces a mitotic block via inhibition of polo-like kinase 1 and has shown remarkable anti-leukemic activity when combined with low-dose cytarabine. We have demonstrated that AML cells are highly vulnerable to cell death in mitosis yet manage to escape a mitotic block through mitotic slippage by sustained proteasome-dependent slow degradation of cyclin B. Therefore, we tested whether interfering with mitotic slippage through proteasome inhibition arrests and kills AML cells more efficiently during mitosis. We show that therapeutic doses of bortezomib block the slow degradation of cyclin B during a volasertib-induced mitotic arrest in AML cell lines and patient-derived primary AML cells. In a xenotransplant mouse model of human AML, mice receiving volasertib in combination with bortezomib showed superior disease control compared to mice receiving volasertib alone, highlighting the potential therapeutic impact of this drug combination.

  17. Regulation of Trib2 by an E2F1-C/EBPα feedback loop in AML cell proliferation.

    LENUS (Irish Health Repository)

    Rishi, Loveena


    The loss of regulation of cell proliferation is a key event in leukemic transformation, and the oncogene tribbles (Trib)2 is emerging as a pivotal target of transcription factors in acute leukemias. Deregulation of the transcription factor E2F1, normally repressed by CCAAT enhancer-binding protein α (C\\/EBPα)-p42, occurs in acute myeloid leukemia (AML), resulting in the perturbation of cell cycle and apoptosis, emphasizing its importance in the molecular pathogenesis of AML. Here we show that E2F family members directly regulate Trib2 in leukemic cells and identify a feedback regulatory loop for E2F1, C\\/EBPα, and Trib2 in AML cell proliferation and survival. Further analyses revealed that E2F1-mediated Trib2 expression was repressed by C\\/EBPα-p42, and in normal granulocyte\\/macrophage progenitor cells, we detect C\\/EBPα bound to the Trib2 promoter. Pharmacological inhibition of the cell cycle or Trib2 knockdown resulted in a block in AML cell proliferation. Our work proposes a novel paradigm whereby E2F1 plays a key role in the regulation of Trib2 expression important for AML cell proliferation control. Importantly, we identify the contribution of dysregulated C\\/EBPα and E2F1 to elevated Trib2 expression and leukemic cell survival, which likely contributes to the initiation and maintenance of AML and may have significant implications for normal and malignant hematopoiesis.

  18. Enterprise Portals und Enterprise Application Integration - Begriffsbestimmung und Integrationskonzeptionen


    Schelp, Joachim; Winter, Robert


    Unter den Stichworten »Enterprise Portals« und »Enterprise Application Integration« werden neue Herausforderungen an die Applikationsarchitektur der Unternehmungen gestellt. Bei beiden spielt die Integration vorhandener und das Einfügen neuer Applikationen eine große Rolle. Beiden Themen ist gemein, dass sie die Diskussion bestimmter technischer Konzepte aus den vergangenen Jahren fortsetzen: Portale stellen das moderne Frontend dar, über das die verschiedenen E-Business-Konzepte umgesetzt we...

  19. Cyberbullying und Empathie : affektive, kognitive und medienbasierte Empathie im Kontext von Cyberbullying im Kindes- und Jugendalter


    Pfetsch, Jan; Müller, Christin R.; Ittel, Angela


    "Bei medial vermittelter Kommunikation sinkt sowohl die Hemmschwelle für aggressive Verhaltensweisen wie Cyberbullying als auch die Wahrscheinlichkeit empathischer Reaktionen. Im Fokus der vorliegenden Studie mit 979 Schülerinnen und Schülern der 4.-8. Klassen (M=12.01, SD=1.68 Jahre, 55% weiblich) stand die Frage, ob Cyberbullies geringere Ausprägungen für affektive, kognitive und medienbasierte Empathie aufweisen als Unbeteiligte. Empathie wurde im Selbst- und Peerbericht erhoben. Hypothese...

  20. Jung und Alt im Dialog

    Directory of Open Access Journals (Sweden)

    Caroline Baetge


    Full Text Available Rezension zu: Kupser, Thomas, und Ida Pöttinger, Hrsg. 2011. Mediale Brücken: Generationen im Dialog durch aktive Medienarbeit. Gesellschaft - Altern - Medien 3. München: kopaed.

  1. Frauen in Philosophie und Wissenschaft

    Directory of Open Access Journals (Sweden)

    Regina Harzer


    Full Text Available Der von Brigitte Doetsch herausgegebene Band präsentiert die aktuelle Feministische Philosophie und sammelt Beiträge, die Einblick geben in den gegenwärtigen Forschungsstand, wie ihn „Philosophinnen im dritten Jahrtausend“ erreicht haben. Insgesamt neun, zum Teil interdisziplinär ausgerichtete Arbeiten werden vorgestellt. Das Themenspektrum ist weit: Geschichte der Philosophie; Politische Philosophie und Naturphilosophie; Epistemologie; Biopolitik und Bioethik als Bereiche praktischer Philosophie; Forschung über Geschlechterverhältnisse. Alle Beiträge gehen zurück auf eine Vortragsreihe des Braunschweiger Zentrums für Gender Studies ( Leser/-innen erhalten einen guten Überblick über die aktuelle Frauenforschung aus der Sicht theoretischer und praktischer Philosophie.

  2. Gesundheit und Pflege im Alter


    Pfaff, Martin


    Gesundheit und Pflege im Alter : d. Gesundheitsreformgesetz (GRG) ; Möglichkeiten, Grenzen u. weitere Vorschläge / Martin Pfaff ; Klaus Deimer. - In: Expertengespräch "Pflege in der Familie". - Augsburg, 1989. - Getr. Zählung

  3. Editorial: Computerspiele und Videogames in formellen und informellen Bildungskontexten

    Directory of Open Access Journals (Sweden)

    Johannes Fromme


    Full Text Available Computer- und Videospiele sind heute ein selbstverständlicher Bestandteil der Lebenswelt vieler Kinder und Jugendlicher, aber auch von (jüngeren Erwachsenen, die mit diesen neuen Medien aufgewachsen sind. Lange Zeit haben elektronische Bildschirmspiele allenfalls sporadische Beachtung gefunden. Weder in der Medienforschung oder Medienpädagogik noch in der breiteren Öffentlichkeit waren sie ein Gegenstand von breiterem Interesse.* In den letzten knapp zehn Jahren sind Video- und Computerspiele allerdings zunehmend in den Fokus der Aufmerksamkeit gerückt. Dabei sind in der massenmedial vermittelten Öffentlichkeit vor allem Amokläufe in Schulen in einen direkten Zusammenhang mit den Vorlieben (der Täter für bestimmte Computerspiele gebracht worden. Die auch von prominenten Politikern aufgegriffene These lautete, dass gewalthaltige Spiele wie der First Person Shooter «Counterstrike» ein virtuelles Trainingsprogramm für das Töten und daher als wesentliche Ursache solcher Schulmassaker anzusehen seien. Auf der Basis dieser kausalen Wirkungsannahmen bzw. der unterstellten negativen Lern- und Trainingseffekte werden seither immer wieder Forderungen nach einem Verbot solcher «Killerspiele» oder gar nach der Verbannung aller Bildschirmmedien aus den Kinderzimmern abgeleitet. Neben solcher skandalisierter Thematisierung ist aber zunehmend auch eine nüchterne wissenschaftliche Auseinandersetzung zu konstatieren. So haben sich seit Beginn des neuen Jahrtausends die «digital game studies» als interdisziplinäres Forschungsfeld etabliert. Im Jahr 2000 wurde innerhalb der Gesellschaft für Medienwissenschaft z.B. die AG Games gebildet, die sich zu einem wichtigen deutschsprachigen Forum für die wissenschaftliche Beschäftigung mit Computerspielen entwickelt hat, und im Jahr 2002 entstand die internationale Digital Games Research Association (DiGRA, die im September 2009 ihre vierte grosse Konferenz nach 2003, 2005 und 2007 durchgeführt hat

  4. Professionalisierung und Doping im Sport


    Wüterich, Christoph


    Der Beitrag untersucht Zusammenhänge zwischen der zunehmenden Professionalisierung des Sports und dem Anstieg von Dopingvergehen. Er zeigt, dass im historischen Vergleich beide Phänomene nicht neu sind, dass sich die Probleme aufgrund der steigenden Bedeutung des Leistungssports aber zugespitzt haben. Ausgehend von einer juristischen und sozioökonomischen Analyse der Anreize zu Doping werden Lösungsvorschläge entwickelt. The author analyzes the interdependencies between a growing commercia...

  5. Pepsi und Coca ewige Rivallen




    Fast jeder kennt Pepsi und Coca. Man kann sie treffen praktisch in jedem Geschaeft. Dennoch nicht alle wissen, dass diese Firmen Erzrivallen sind und das ihre Rivallitaet sich seit Ewigkeit dauert. In meinem Artikel, welches ich in der Zusammenarbeit mit meinem Vater schrieb versuchte ich den Weg beider Firmen von der Gruendung bis heutigen Tagen zu beschreiben. Auf diesem Weg trafen sich technologische Aenderungen, Gerichtsverhandlungen, sowie geschickte Tricks. Wichtige Rolle spielt auch Ma...

  6. Tax Shield, Insolvenz und Zinsschranke


    Arnold, Sven; Lahmann, Alexander; Schwetzler, Bernhard


    Dieser Beitrag analysiert den Wertbeitrag fremdfinanzierungsbedingter Steuervorteile (Tax Shield) unter realistischen Bedingungen (keine Negativsteuer; mögliche Insolvenz) für unterschiedliche Finanzierungspolitiken. Zusätzlich wird der Effekt der sogenannten Zinsschranke auf den Wert des Tax Shield ermittelt. Die Bewertung des Tax Shield mit und ohne Zinsschranke findet im einperiodigen Fall auf der Basis von Optionspreismodellen und im mehrperiodigen Fall auf der Basis von Monte Carlo Simul...

  7. Spliceosomal gene aberrations are rare, coexist with oncogenic mutations, and are unlikely to exert a driver effect in childhood MDS and JMML

    NARCIS (Netherlands)

    S. Hirabayashi (Shinsuke); C. Flotho (Christian); J. Moetter (Jessica); M. Heuser (Michael); H. Hasle (Henrik); B. Gruhn (Bernd); T. Klingebiel (Thomas); F. Thol (Felicitas); B. Schlegelberger (Brigitte); I. Baumann (Irith); B. Strahm (Brigitte); J. Stary (Jan); F. Locatelli (Franco); M. Zecca (Marco); E. Bergstraesser (Eva); M.N. Dworzak (Michael); M.M. van den Heuvel-Eibrink (Marry); B. de Moerloose (Barbara); S. Ogawa (Susumu); C.M. Niemeyer (Charlotte); M. Wlodarski (Marcin)


    textabstractSomatic mutations of the spliceosomal machinery occur frequently in adult patients with myelodysplastic syndrome (MDS). We resequenced SF3B1, U2AF35, and SRSF2 in 371 children with MDS or juvenile myelomonocytic leukemia. We found missense mutations in 2 juvenile myelomonocytic leukemia

  8. Aplastic Anemia and MDS International Foundation (AAMDSIF): Bone marrow failure disease scientific symposium 2016. (United States)

    Zeidan, Amer M; Battiwalla, Minoo; Berlyne, Deborah; Winkler, Thomas


    Patients with acquired and inherited bone marrow failure syndromes (BMFS) have ineffective hematopoiesis due to impairments of the hematopoietic stem cell compartment. Common manifestations of BMFS include varying degrees of peripheral blood cytopenias and, sometimes, progression to acute myelogenous leukemia. Research efforts have been made all over the world to improve understanding of the pathogenesis of these diseases and their clinical implications. The Aplastic Anemia and MDS International Foundation (AAMDSIF) is an independent nonprofit organization whose mission is to help patients and family members cope with BMFS. Here, we summarize recent scientific discoveries in several BMFS that were presented at the fifth International Bone Marrow Failure Disease Scientific Symposium 2016 that AAMDSIF sponsored on March 17-18, 2016, in Rockville, Maryland. Copyright © 2016 Elsevier Ltd. All rights reserved.

  9. Additive Construction with Mobile Emplacement (ACME) / Automated Construction of Expeditionary Structures (ACES) Materials Delivery System (MDS) (United States)

    Mueller, R. P.; Townsend, I. I.; Tamasy, G. J.; Evers, C. J.; Sibille, L. J.; Edmunson, J. E.; Fiske, M. R.; Fikes, J. C.; Case, M.


    The purpose of the Automated Construction of Expeditionary Structures, Phase 3 (ACES 3) project is to incorporate the Liquid Goods Delivery System (LGDS) into the Dry Goods Delivery System (DGDS) structure to create an integrated and automated Materials Delivery System (MDS) for 3D printing structures with ordinary Portland cement (OPC) concrete. ACES 3 is a prototype for 3-D printing barracks for soldiers in forward bases, here on Earth. The LGDS supports ACES 3 by storing liquid materials, mixing recipe batches of liquid materials, and working with the Dry Goods Feed System (DGFS) previously developed for ACES 2, combining the materials that are eventually extruded out of the print nozzle. Automated Construction of Expeditionary Structures, Phase 3 (ACES 3) is a project led by the US Army Corps of Engineers (USACE) and supported by NASA. The equivalent 3D printing system for construction in space is designated Additive Construction with Mobile Emplacement (ACME) by NASA.

  10. Neue Shandite und Parkerite. Darstellung und röntgenographische Charakterisierung


    Anusca, Irina


    Das Ziel dieser Arbeit war es, neue Verbindungen mit Shandit- und Parkeritstruktur zu darstellen und mittels röntgenographischen Methoden (Pulverdiffraktometrie und Einkristallanalyse), das thermische Verhalten durch DTA / DSC - Messungen und Elektronenmikroskopische Untersuchungen (REM, EDX) zu charakterisieren. Die vorliegende Arbeit ist wie folgt im zwei Themen gegliedert: Shandite und Parkerite. Der ersten Teil dieser Arbeit befaßt sich mit metallreichen ternären Chalkogeniden M3A2X2, ...

  11. Molekulargenetische Studie zur Verbreitung und Interaktion von PCV-2 bei Haus- und Wildschweinen


    Bronnert, Bastian Balthasar Marcel


    Im Rahmen der vorliegenden Arbeit wurden Wild- und Hausschweingewebeproben aus den Jahren 2005 bis 2008 mittels nested PCR auf das Vorkommen von PCV-2 untersucht und die positiv getesteten Proben mittels Realtime PCR quantifiziert. Zusätzlich wurden die Proben im Institut für Pathologie der Justus-Liebig-Universität histologisch und immunhistologisch untersucht (Dissertation Hohloch). Ziel war es das Vorkommen von PCV-2 und die Häufigkeit von PCV-2 assoziierter Erkankungen bei Haus- und Wilds...

  12. Vom Stabilitäts- und Wachstumsgesetz zum Wohlstands- und Nachhaltigkeitsgesetz


    Koll, Willi


    Das Stabilitäts- und Wachstumsgesetz wird bald 50 Jahre alt. Neue Herausforderungen erfordern eine Wirtschaftspolitik, die weit über die Ziele des Gesetzes hinausweist. Sie muss wirtschaftliches Wachstum und Stabilität mit den Zielen fiskalischer, sozialer und ökologischer Nachhaltigkeit auf nationaler und europäischer Ebene verbinden. Der Autor gibt einen Über blick über solche umfassenden Zielsysteme und leitet daraus ab, wie eine derart erweiterte wirtschaftspolitische Agenda in ein Wohlst...

  13. Interconnectedness und digitale Texte

    Directory of Open Access Journals (Sweden)

    Detlev Doherr


    Full Text Available Zusammenfassung Die multimedialen Informationsdienste im Internet werden immer umfangreicher und umfassender, wobei auch die nur in gedruckter Form vorliegenden Dokumente von den Bibliotheken digitalisiert und ins Netz gestellt werden. Über Online-Dokumentenverwaltungen oder Suchmaschinen können diese Dokumente gefunden und dann in gängigen Formaten wie z.B. PDF bereitgestellt werden. Dieser Artikel beleuchtet die Funktionsweise der Humboldt Digital Library, die seit mehr als zehn Jahren Dokumente von Alexander von Humboldt in englischer Übersetzung im Web als HDL (Humboldt Digital Library kostenfrei zur Verfügung stellt. Anders als eine digitale Bibliothek werden dabei allerdings nicht nur digitalisierte Dokumente als Scan oder PDF bereitgestellt, sondern der Text als solcher und in vernetzter Form verfügbar gemacht. Das System gleicht damit eher einem Informationssystem als einer digitalen Bibliothek, was sich auch in den verfügbaren Funktionen zur Auffindung von Texten in unterschiedlichen Versionen und Übersetzungen, Vergleichen von Absätzen verschiedener Dokumente oder der Darstellung von Bilden in ihrem Kontext widerspiegelt. Die Entwicklung von dynamischen Hyperlinks auf der Basis der einzelnen Textabsätze der Humboldt‘schen Werke in Form von Media Assets ermöglicht eine Nutzung der Programmierschnittstelle von Google Maps zur geographischen wie auch textinhaltlichen Navigation. Über den Service einer digitalen Bibliothek hinausgehend, bietet die HDL den Prototypen eines mehrdimensionalen Informationssystems, das mit dynamischen Strukturen arbeitet und umfangreiche thematische Auswertungen und Vergleiche ermöglicht. Summary The multimedia information services on Internet are becoming more and more comprehensive, even the printed documents are digitized and republished as digital Web documents by the libraries. Those digital files can be found by search engines or management tools and provided as files in usual formats as

  14. Isotopes and innovation: MDS Nordion's first fifty years, 1946-1996

    International Nuclear Information System (INIS)

    Litt, P.


    Few people realize that Canada leads in the world in the production of radio isotopes, the raw material of nuclear medicine and high-tech scanners, and in their use in medicine and industry. In Isotopes and Innovation the author gives an in-depth look at MDS Nordion, a company that started as the radium sales department of Eldorado Mining and Refining, the Canadian uranium producer that was a key strategic resource for the Allies during the race to build the nuclear bomb, and went on to become the world?s leading producer of radioisotopes. When radium began to be used as a cancer treatment, Eldorado quickly became familiar with the medical marketplace and adept at developing products that could solve clinical problems and, more important, save lives. When Canadian nuclear reactors at Chalk River began producing radioisotopes that outperformed radium, Eldorado's radium sales department was transferred to a new crown corporation, Atomic Energy of Canada Limited, created to manage Canada's nuclear research establishment. The new company developed many useful applications for radioisotopes, including cobalt-60 cancer therapy machines and industrial sterilization plants. Bought by Medical Data Services Inc. in the early 1990s, MDS Nordion was a runaway success, creator and sole proprietor of several market-leading products. Isotopes and Innovation describes how a company capitalized on the byproducts of Canada's unique nuclear research program to attain a commanding international position in extremely specialized and demanding high-tech markets, a saga in which innovative research and enterprising global marketing have brought commercial success and saved countless lives around the world

  15. Isotopes and innovation: MDS Nordion's first fifty years, 1946-1996

    Energy Technology Data Exchange (ETDEWEB)

    Litt, P


    Few people realize that Canada leads in the world in the production of radio isotopes, the raw material of nuclear medicine and high-tech scanners, and in their use in medicine and industry. In Isotopes and Innovation the author gives an in-depth look at MDS Nordion, a company that started as the radium sales department of Eldorado Mining and Refining, the Canadian uranium producer that was a key strategic resource for the Allies during the race to build the nuclear bomb, and went on to become the world?s leading producer of radioisotopes. When radium began to be used as a cancer treatment, Eldorado quickly became familiar with the medical marketplace and adept at developing products that could solve clinical problems and, more important, save lives. When Canadian nuclear reactors at Chalk River began producing radioisotopes that outperformed radium, Eldorado's radium sales department was transferred to a new crown corporation, Atomic Energy of Canada Limited, created to manage Canada's nuclear research establishment. The new company developed many useful applications for radioisotopes, including cobalt-60 cancer therapy machines and industrial sterilization plants. Bought by Medical Data Services Inc. in the early 1990s, MDS Nordion was a runaway success, creator and sole proprietor of several market-leading products. Isotopes and Innovation describes how a company capitalized on the byproducts of Canada's unique nuclear research program to attain a commanding international position in extremely specialized and demanding high-tech markets, a saga in which innovative research and enterprising global marketing have brought commercial success and saved countless lives around the world.

  16. Impact Of Mutation-derived Antigens In Immune Recognition Of Hematological Malignancies, Specifically Myeloid Dysplastic Syndromes (MDS)

    DEFF Research Database (Denmark)

    Saini, Sunil Kumar; Dorfmüller, S.; Bjerregaard, Anne-Mette


    Mutation-derived neoepitopes have been suggested as a major component for immune recognition of solid tumors with a high mutational load, e.g. Melanoma and Non-Small-Cell Lung Cancer (NSCLC). Myelodysplastic syndromes (MDS) are a heterogeneous group of myeloid neoplasms characterized by increasing...

  17. Wheat Mds-1 encodes a heat-shock protein and governs susceptibility towards the Hessian fly gall midge (United States)

    Plant pests including insects must manipulate plants in order to utilize the nutrition and environment of the host. Here, we show that the heat-shock protein gene Mayetiola destructor susceptibility gene-1 (Mds-1) is a major susceptibility gene in wheat that allows the gall midge M. destructor, com...

  18. Allogeneic hematopoietic stem cell transplant in adult patients with myelodysplastic syndrome/myeloproliferative neoplasm (MDS/MPN) overlap syndromes. (United States)

    Sharma, Prashant; Shinde, Shivani S; Damlaj, Moussab; Hefazi Rorghabeh, Mehrdad; Hashmi, Shahrukh K; Litzow, Mark R; Hogan, William J; Gangat, Naseema; Elliott, Michelle A; Al-Kali, Aref; Tefferi, Ayalew; Patnaik, Mrinal M


    MDS/MPN (myelodysplastic syndrome/myeloproliferative neoplasm) overlap syndromes are myeloid malignancies for which allogeneic hematopoietic stem cell transplant (allo-HSCT) is potentially curative. We describe transplant outcomes of 43 patients - 35 with chronic myelomonocytic leukemia, CMML (of which 17 had blast transformation, BT) and eight with MDS/MPN-unclassifiable (MDS/MPN,U). At median follow-up of 21 months, overall survival (OS), cumulative incidence of relapse (CIR) and non-relapse mortality (NRM) were 55%, 29%, and 25% respectively in CMML without BT and 47%, 40%, and 34% respectively in CMML with BT. Higher HSCT-comorbidity index (HSCT-CI >3 versus ≤3; p = 0.015) and splenomegaly (p = 0.006) predicted worse OS in CMML without BT. In CMML with BT, engraftment failure (p = 0.006) and higher HSCT-CI (p = 0.03) were associated with inferior OS, while HSCT within 1-year of diagnosis was associated with improved OS (p = 0.045). In MDS/MPN,U, at median follow-up of 15 months, OS, CIR, and NRM were 62%, 30%, and 14%, respectively.

  19. Role of the Phosphorylation of mTOR in the Differentiation of AML Cells Triggered with CD44 Antigen

    KAUST Repository

    Darwish, Manar M


    Acute myeloid leukemia (AML) is a hematological disorder characterized by blockage of differentiation of myeloblasts. To date, the main therapy for AML is chemotherapy. Yet, studies are seeking a better treatment to enhance the survival rate of patients and minimize the relapsing of the disease. Since the major problem in these cells is that they are arrested in cellular differentiation, drugs that could induce their differentiation have proven to be efficient and of major interest for AML therapy. CD44 triggering appeared as a promising target for AML therapy as it has been shown that specific monoclonal antibodies, such as A3D8 and H90, reversed the blockage of differentiation, inhibited the proliferation of all AML subtypes, and in some cases, induced cell apoptosis. Studies conducted in our laboratory have added strength to these antibodies as potential treatment for AML. Indeed, our laboratory found that treating HL60 cells with A3D8 shows a decrease in the phosphorylation of the mammalian target of Rapamycin (mTOR) kinase correlated with the inhibition of proliferation/induction of differentiation of AML cells.The relationship between the induction of differentiation and the inhibition of proliferation and the decrease of mTOR phosphorylation remains to be clarified. To study the importance of the de-phosphorylation of mTOR and the observed effect of CD44 triggering on differentiation and/or proliferation, we sought to prepare phospho-mimic mutants of the mTOR kinase that will code for a constitutively phosphorylated form of mTOR and used two main methods to express this mutant in HL60 cells: lentiviral and simple transfection (cationic-liposomal transfection).

  20. Pubertal development and fertility in survivors of childhood acute myeloid leukemia treated with chemotherapy only: a NOPHO-AML study. (United States)

    Molgaard-Hansen, Lene; Skou, Anne-Sofie; Juul, Anders; Glosli, Heidi; Jahnukainen, Kirsi; Jarfelt, Marianne; Jónmundsson, Guðmundur K; Malmros, Johan; Nysom, Karsten; Hasle, Henrik


    More than 60% of children with acute myeloid leukemia (AML) become long-term survivors. Most are cured using chemotherapy without hematopoietic stem cell transplantation (HSCT). We report on pubertal development and compare self-reported parenthood among AML survivors and their siblings. We included 137 children treated for AML according to the Nordic Society of Pediatric Hematology and Oncology (NOPHO)-AML-84, -88, and -93 trials, who were alive by June 2007. Patients with relapse or treated with HSCT were excluded. AML survivors participated in a physical and biochemical examination (n = 102) and completed a questionnaire (n = 101). One of their siblings completed an identical questionnaire (n = 84). At a median follow-up of 11 years (range 5-25) after diagnosis of AML the survivors (median age 16 years, range 5-36) were either prepubertal or had entered puberty normally. Serum levels of FSH, LH, testosterone, estradiol, sex hormone binding globulin (SHBG), inhibin A and B, and testicular volumes were within normal ranges. Anti-Müllerian hormone (AMH) levels were decreased in 5 of 40 postpubertal females. Mean reported age at menarche was 13.1 (range 11-17) years. Among survivors 15 years of age or older 31% of females reported pregnancies and 9% of males reported pregnancies in their partners, rates comparable with the frequency reported by their siblings. Most AML survivors treated with chemotherapy had normal pubertal development and fertility, however, AMH levels were decreased in 13% of postpubertal females. Longer follow-up is necessary to evaluate possible risk of premature ovarian failure. © 2013 Wiley Periodicals, Inc.

  1. Gosvig und das Problem der Geschichte

    DEFF Research Database (Denmark)

    Wentzer, Thomas Schwarz


    Der Essay geht der Frage nach, wieso so viele philosophische Bücher, insbesondere innerhalb der sogenannten 'kontinentalen' Philosophie des 20. Jhs, einen Titel tragen, der durch die Struktur 'x und y' gekennzeichnet ist. Hat Heideggers 'Sein und Zeit' auch hier Schule gemacht? Wenn ja, wie so? U...... These, dass die Iteration des 'und' tatsächlich und in Kontrast zur Genetivkonstruktion der Idealisten ('Phänomenologie des Geistes') die Geschichtlichkeit im Zeitalter postsubjektivistischen Denkens reflektiert....

  2. Decitabine improves progression-free survival in older high-risk MDS patients with multiple autosomal monosomies: results of a subgroup analysis of the randomized phase III study 06011 of the EORTC Leukemia Cooperative Group and German MDS Study Group

    NARCIS (Netherlands)

    Lubbert, M.; Suciu, S.; Hagemeijer, A.; Ruter, B.; Platzbecker, U.; Giagounidis, A.; Selleslag, D.; Labar, B.; Germing, U.; Salih, H.R.; Muus, P.; Pfluger, K.H.; Schaefer, H.E.; Bogatyreva, L.; Aul, C.; Witte, T.J.M. de; Ganser, A.; Becker, H.; Huls, G.A.; Helm, L. van der; Vellenga, E.; Baron, F.; Marie, J.P.; Wijermans, P.W.; Group, E.L.; German, M.D.S.S.G. the


    In a study of elderly AML patients treated with the hypomethylating agent decitabine (DAC), we noted a surprisingly favorable outcome in the (usually very unfavorable) subgroup with two or more autosomal monosomies (MK2+) within a complex karyotype (Lubbert et al., Haematologica 97:393-401, 2012).

  3. Design of the randomized, Phase III, QUAZAR AML Maintenance trial of CC-486 (oral azacitidine) maintenance therapy in acute myeloid leukemia. (United States)

    Roboz, Gail J; Montesinos, Pau; Selleslag, Dominik; Wei, Andrew; Jang, Jun-Ho; Falantes, Jose; Voso, Maria T; Sayar, Hamid; Porkka, Kimmo; Marlton, Paula; Almeida, Antonio; Mohan, Sanjay; Ravandi, Farhad; Garcia-Manero, Guillermo; Skikne, Barry; Kantarjian, Hagop


    Older patients with acute myeloid leukemia (AML) have worse rates of complete remission and shorter overall survival than younger patients. The epigenetic modifier CC-486 is an oral formulation of azacitidine with promising clinical activity in patients with AML in Phase I studies. The Phase III, randomized, double-blind, placebo-controlled QUAZAR AML Maintenance trial (CC-486-AML-001) examines CC-486 maintenance therapy (300 mg/day for 14 days of 28-day treatment cycles) for patients aged ≥55 years with AML in first complete remission. The primary end point is overall survival. Secondary end points include relapse-free survival, safety, health-related quality of life and healthcare resource utilization. This trial will investigate whether CC-486 maintenance can prolong remission and improve survival for older patients with AML.

  4. Mensch und Maschine in Übersetzungsprozessen

    DEFF Research Database (Denmark)

    Hansen, Gyde


    gebrauchstauglich sein. In meinem empirischen Projekt zur Erforschung notwendiger Kompetenzen, zum Übersetzen, Revidieren und zum Pre- und Post-Editing, TraREdit, arbeite ich mit den Sprachen Deutsch, Dänisch und Englisch. Trotz offensichtlicher Mängel von Maschinenübersetzungen muss man erkennen, dass diese besser...

  5. Sprachvermittlung und Spracherwerb in Afrika. Deutsch nach ...

    African Journals Online (AJOL)

    erlernende Fremdsprache richtig und auf hohem Niveau sprechen zu lernen. Lehrende sollten alles daransetzen zu verhindern, dass die Lernenden in dieser Vereinfachungsphase stehen bleiben und ihre Sprache fossilieren. Die Bewusstmachung der Ähnlichkeiten von Zulu und. Deutsch kann dazu beitragen, indem man ...

  6. Zustand und Perspektiven der Kapitalmarktfinanzierung in Deutschland

    DEFF Research Database (Denmark)

    Beck, Thorsten; Kaserer, Christoph; Rapp, Marc Steffen


    Die Autoren haben sich im Rahmen des durch das Bundesministerium für Wirtschaft und Energie (BMWi) in Auftrag gegebenen Forschungsprojekts „Beteiligungs- und Kapitalmarktfinanzierung im deutschen Finanzsystem: Zustand und Entwicklungsperspektiven“ (Dienstleistungsprojekt I C 4 -27/14) mit dem Zus...

  7. Data Science und Analytics in Bibliotheken

    Directory of Open Access Journals (Sweden)

    José Luis Preza


    Full Text Available Bibliotheken sind in einer priviligierten Situation: Sie verwalten riesige Mengen von Daten und Informationen. Data Science und Analytics-Methoden ermöglichen es Bibliotheken, den Inhalt, den sie verwalten, voll auszunutzen, um den Nutzern bessere Informationen, Suche und Empfehlungen zu bieten.

  8. Pressurized grout remote backfilling at AML sites near Beulah and Zap, North Dakota

    International Nuclear Information System (INIS)

    Weiner, E.J.; Dodd, W.E.


    The Abandoned Mine Lands (AML) Division of the North Dakota Public Service Commission (PSC) is charged with the reclamation of hazardous abandoned mine sites in North Dakota. Several underground lignite coalmines were operated near the cities of Beulah and Zap, North Dakota, from the early 1900's until about 1955. Coal seams in this area were relatively thick and the overburden generally shallow. As these mines have deteriorated with time, deep collapse features, or sinkholes, have surfaced in many areas. These features are very dangerous, especially when they occur at or near residential and commercial areas and public roads. In the past five years, sinkholes have surfaced beneath a commercial building (boat dealership, lounge, and gas station) and beneath a nearby occupied mobile home north of Beulah. sinkholes have also surfaced near KHOL Radio Station in Beulah and in the right of way of a public road south of Zap. The AML Division has conducted several emergency sinkhole-filling projects in these areas. In 1995--97, the AML Division conducted exploratory drilling which confirmed the presence of collapsing underground mines at these sites. The remediation of these sites around Beulah/Zap will take place over several years and involve three or more separate contracts due to budget considerations. In 1997, the AML Division began reclamation at these sties utilizing pressurized grout remote backfilling. In this technique, a cementitious grout is pumped through cased drill holes directly into the mine cavities to fill them and thereby stabilize the surface from collapse. The successful contractor for Phase One of the project was The Concrete Doctor, Inc. (TCDI). This paper will concentrate on Phase One of this work performed from June through September 1997. This project is especially interesting because grout was pumped through holes drilled inside the occupied commercial building. Grout was also pumped through angled holes that intercepted mined workings directly

  9. Pressurized grout remote backfilling at AML sites near Beulah and Zap, North Dakota

    Energy Technology Data Exchange (ETDEWEB)

    Weiner, E.J.; Dodd, W.E.


    The Abandoned Mine Lands (AML) Division of the North Dakota Public Service Commission (PSC) is charged with the reclamation of hazardous abandoned mine sites in North Dakota. Several underground lignite coalmines were operated near the cities of Beulah and Zap, North Dakota, from the early 1900's until about 1955. Coal seams in this area were relatively thick and the overburden generally shallow. As these mines have deteriorated with time, deep collapse features, or sinkholes, have surfaced in many areas. These features are very dangerous, especially when they occur at or near residential and commercial areas and public roads. In the past five years, sinkholes have surfaced beneath a commercial building (boat dealership, lounge, and gas station) and beneath a nearby occupied mobile home north of Beulah. sinkholes have also surfaced near KHOL Radio Station in Beulah and in the right of way of a public road south of Zap. The AML Division has conducted several emergency sinkhole-filling projects in these areas. In 1995--97, the AML Division conducted exploratory drilling which confirmed the presence of collapsing underground mines at these sites. The remediation of these sites around Beulah/Zap will take place over several years and involve three or more separate contracts due to budget considerations. In 1997, the AML Division began reclamation at these sties utilizing pressurized grout remote backfilling. In this technique, a cementitious grout is pumped through cased drill holes directly into the mine cavities to fill them and thereby stabilize the surface from collapse. The successful contractor for Phase One of the project was The Concrete Doctor, Inc. (TCDI). This paper will concentrate on Phase One of this work performed from June through September 1997. This project is especially interesting because grout was pumped through holes drilled inside the occupied commercial building. Grout was also pumped through angled holes that intercepted mined workings

  10. Tumor Lysis Syndrome (TLS following intrathecal chemotherapy in a child with acute myelogenous leukemia (AML

    Directory of Open Access Journals (Sweden)

    Chana L. Glasser, MD


    Full Text Available Tumor Lysis Syndrome (TLS is a well-known complication of induction therapy for hematologic malignancies. It is characterized by rapid breakdown of malignant white blood cells (WBCs leading to metabolic derangements and serious morbidity if left untreated. Most commonly, TLS is triggered by systemic chemotherapy, however, there have been case reports of TLS following intrathecal (IT chemotherapy, all in patients with acute lymphoblastic leukemia (ALL/lymphoma. Here, we report the first case of a patient with acute myelogenous leukemia (AML who developed TLS following a single dose of IT cytosine arabinoside (Ara-C.

  11. Unveiling the role of PAK2 in CD44 mediated inhibition of proliferation, differentiation and apoptosis in AML cells

    KAUST Repository

    Aldehaiman, Mansour M.


    Acute myeloid leukemia (AML) is a heterogeneous disease characterized by the accumulation of immature nonfunctional highly proliferative hematopoietic cells in the blood, due to a blockage in myeloid differentiation at various stages. Since the success of the differentiation agent, All-trans retinoic acid (ATRA), in the treatment of acute promyelocytic leukemia (APL), much effort has gone into trying to find agents that are able to differentiate AML cells and specifically the leukemic stem cell (LSC). CD44 is a cell surface receptor that is over-expressed on AML cells. When bound to anti-CD44 monoclonal antibodies (mAbs), this differentiation block is relieved in AML cells and their proliferation is reduced. The molecular mechanisms that AML cells undergo to achieve this reversal of their apparent phenotype is not fully understood. To this end, we designed a study using quantitative phosphoproteomics approaches aimed at identifying differences in phosphorylation found on proteins involved in signaling pathways post-treatment with CD44-mAbs. The Rho family of GTPases emerged as one of the most transformed pathways following the treatment with CD44-mAbs. The P21 activated kinase 2(PAK2), a target of the Rho family of GTPases, was found to be differentially phosphorylated in AML cells post-treatment with CD44-mAbs. This protein has been found to possess a role similar to that of a switch that determines whether the cell survives or undergoes apoptosis. Beyond confirming these results by various biochemical approaches, our study aimed to determine the effect of knock down of PAK2 on AML cell proliferation and differentiation. In addition, over-expression of PAK2 mutants using plasmid cloning was also explored to fully understand how levels of PAK2 as well as the alteration of specific phospohorylation sites could alter AML cell responses to CD44-mAbs. Results from this study will be important in determining whether PAK2 could be used as a potential therapeutic target

  12. Marktkonstitution und Regulierung der unabhängigen Film- und Fernsehproduktion : Staat, Verbände und Gewerkschaften im deutsch-britischen Vergleich


    Elbing, Sabine; Voelzkow, Helmut


    "In einem internationalen Vergleich von Deutschland und Großbritannien wird untersucht, welche Beiträge die staatliche Politik und die Wirtschafts- und Sozialpartner (Wirtschafts- und Arbeitgeberverbände sowie Gewerkschaften) zur Förderung der unabhängigen Film- und Fernsehproduktion leisten. Es wird gezeigt, dass die britische Medienpolitik die Position der unabhängigen Film- und Fernsehproduktion gegenüber den Fernsehsendern gestärkt hat. In Deutschland hat die Medienpolitik darauf verzicht...

  13. Design and kinetic analysis of hammerhead ribozyme and DNAzyme that specifically cleave TEL-AML1 chimeric mRNA

    International Nuclear Information System (INIS)

    Choi, Woo-Hyung; Choi, Bo-Ra; Kim, Jae Hyun; Yeo, Woon-Seok; Oh, Sangtaek; Kim, Dong-Eun


    In order to develop the oligonucleotides to abolish an expression of TEL-AML1 chimeric RNA, which is a genetic aberration that causes the acute lymphoblastic leukemia (ALL), hammerhead ribozymes and deoxyoligoribozymes that can specifically cleave TEL-AML1 fusion RNA were designed. Constructs of the deoxyribozyme with an asymmetric substrate binding arm (Dz26) and the hammerhead ribozyme with a 4 nt-bulged substrate binding arm in the stem III (buRz28) were able to cleave TEL-AML1 chimeric RNA specifically at sites close to the junction in vitro, without cleaving the normal TEL and AML1 RNA. Single-turnover kinetic analysis under enzyme-excess condition revealed that the buRz28 is superior to the Dz26 in terms of substrate binding and RNA-cleavage. In conjunction with current progress in a gene-delivery technology, the designed oligonucleotides that specifically cleave the TEL-AML1 chimeric mRNA are hoped to be applicable for the treatment of ALL in vivo

  14. Effects of TLR agonists on maturation and function of 3-day dendritic cells from AML patients in complete remission

    Directory of Open Access Journals (Sweden)

    Merk Martina


    Full Text Available Abstract Background Active dendritic cell (DC immunization protocols are rapidly gaining interest as therapeutic options in patients with acute myeloid leukemia (AML. Here we present for the first time a GMP-compliant 3-day protocol for generation of monocyte-derived DCs using different synthetic Toll-like receptor (TLR agonists in intensively pretreated patients with AML. Methods Four different maturation cocktails were compared for their impact on cell recovery, phenotype, cytokine secretion, migration, and lymphocyte activation in 20 AML patients and 25 healthy controls. Results Maturation cocktails containing the TLR7/8 agonists R848 or CL075, with and without the addition of the TLR3 agonist poly(I:C, induced DCs that had a positive costimulatory profile, secreted high levels of IL-12(p70, showed chemotaxis to CCR7 ligands, had the ability to activate NK cells, and efficiently stimulated antigen-specific CD8+ T cells. Conclusions Our results demonstrate that this approach translates into biologically improved DCs, not only in healthy controls but also in AML patients. This data supports the clinical application of TLR-matured DCs in patients with AML for activation of innate and adaptive immune responses.

  15. [Die baltischen Lande im Zeitalter der Reformation und Konfessionalisierung : Livland, Estland, Ösel, Ingermanland, Kurland und Lettgallen : Stadt, Land und Konfession 1500-1721. Teil 4. Hrsg. von Matthias Asche, Werner Buchholtz und Anton Schindlin

    Index Scriptorium Estoniae

    Maasing, Madis, 1984-


    Arvustus: Die baltischen Lande im Zeitalter der Reformation und Konfessionalisierung : Livland, Estland, Ösel, Ingermanland, Kurland und Lettgallen : Stadt, Land und Konfession 1500-1721. Teil 4. (Katholisches Leben und Kirchenreform im Zeitalter der Glaubensspaltung, 72). Hrsg. von Matthias Asche, Werner Buchholtz und Anton Schindling. Verlag Aschendorff. Münster 2012

  16. GIS und Fernerkundung für Landschaftsmonitoring und Landschaftsplanung (United States)

    Blaschke, Thomas


    Der Beitrag beleuchtet die Rolle der Geographischen Informationsverarbeitung hinsichtlich der Aufgaben in der Umweltüberwachung. Dabei wird über etablierte "sektorale" Umweltbeobachtungssysteme (Boden, Wasser, Luft) hinaus zunehmend der Bedarf an einer integrativen Betrachtung der Landschaft deutlich, insbesondere in mittleren bis kleinen Maßstäben. Wie verändern sich ganze Landschaften in Deutschland, in Europa? Welches sind Bereiche kritischer Abnahme landschaftlicher Diversität? Wie können landschaftliche Vielfalt und Eigenart erhalten beziehungsweise deren Erhalt überwacht werden? Diese und weitere Fragen drängen sich vor allem bei der Erstellung langfristiger Szenarien der Veränderung ganzer Landschaften und in der Nachhaltigkeitsdiskussion auf.

  17. Health-related quality of life in lower-risk MDS patients compared with age- and sex-matched reference populations: a European LeukemiaNet study. (United States)

    Stauder, Reinhard; Yu, Ge; Koinig, Karin A; Bagguley, Tim; Fenaux, Pierre; Symeonidis, Argiris; Sanz, Guillermo; Cermak, Jaroslav; Mittelman, Moshe; Hellström-Lindberg, Eva; Langemeijer, Saskia; Holm, Mette Skov; Mądry, Krzysztof; Malcovati, Luca; Tatic, Aurelia; Germing, Ulrich; Savic, Aleksandar; van Marrewijk, Corine; Guerci-Bresler, Agnès; Luño, Elisa; Droste, Jackie; Efficace, Fabio; Smith, Alex; Bowen, David; de Witte, Theo


    In myelodysplastic syndromes (MDS), health-related quality of life (HRQoL) represents a relevant patient-reported outcome, which is essential in individualized therapy planning. Prospective data on HRQoL in lower-risk MDS remain rare. We assessed HRQOL by EQ-5D questionnaire at initial diagnosis in 1690 consecutive IPSS-Low/Int-1 MDS patients from the European LeukemiaNet Registry. Impairments were compared with age- and sex-matched EuroQol Group norms. A significant proportion of MDS patients reported moderate/severe problems in the dimensions pain/discomfort (49.5%), mobility (41.0%), anxiety/depression (37.9%), and usual activities (36.1%). Limitations in mobility, self-care, usual activities, pain/discomfort, and EQ-VAS were significantly more frequent in the old, in females, and in those with high co-morbidity burden, low haemoglobin levels, or red blood cells transfusion need (p MDS patients (p MDS-related restrictions in the dimension mobility were most prominent in males, and in older people (p MDS experience a pronounced reduction in HRQoL and a clustering of restrictions in distinct dimensions of HRQoL as compared with reference populations.

  18. [mRNA expression of notch ligand-delta-like-1 and jagged-1 in mesenchymal stem cells of MDS patients]. (United States)

    Fei, Cheng-Ming; Gu, Shu-Cheng; Zhao, You-Shan; Guo, Juan; Li, Xiao; Chang, Chun-Kang


    This study was aimed to investigated the mRNA expression levels of Notch ligands- Delta-like-1 and Jagged-1 in bone marrow mesenchymal stem cells of patients with myelodysplastic syndrome (MDS), and to explore their relation with onset of MDS. Bone marrow mesenchymal stem cells of 38 patients with MDS and 16 normal subjects as control were collected to detect mRNA expression of Delta-like-1 and Jagged-1 by using real-time quantitative polymerase chain reaction. The results showed that the expression levels of Delta-like-1 and Jagged-1 in mesenchymal stem cells of MDS patients were significantly higher than that in normal controls (P MDS patients (r = 0.502, P MDS patients with abnormal karyotypes were significantly higher than those in MDS patients with normal karyotypes (P 0.05). It is concluded that the changes of Delta-like-1 and Jagged-1 expression level in MSC may play a role in the pathogenesis of myelodysplastic syndrome.

  19. Progression of MDS-UPDRS Scores Over Five Years in De Novo Parkinson Disease from the Parkinson's Progression Markers Initiative Cohort. (United States)

    Holden, Samantha K; Finseth, Taylor; Sillau, Stefan H; Berman, Brian D


    The Movement Disorder Society Unified Parkinson Disease Rating Scale (MDS-UDPRS) is a commonly used tool to measure Parkinson disease (PD) progression. Longitudinal changes in MDS-UPDRS scores in de novo PD have not been established. Determine progression rates of MDS-UPDRS scores in de novo PD. 362 participants from the Parkinson's Progression Markers Initiative, a multicenter longitudinal cohort study of de novo PD, were included. Longitudinal progression of MDS-UPDRS total and subscale scores were modeled using mixed model regression. MDS-UPDRS scores increased in a linear fashion over five years in de novo PD. MDS-UPDRS total score increased an estimated 4.0 points/year, Part I 0.25 points/year, Part II 1.0 points/year, and Part III 2.4 points/year. The expected average progression of MDS-UPDRS scores in de novo PD from this study can assist in clinical monitoring and provide comparative data for detection of disease modification in treatment trials.

  20. Ethik, Recht und Theologie. Reproduktionstechnologien in Polen

    Directory of Open Access Journals (Sweden)

    Susanne Lettow


    Full Text Available Die bisherigen Debatten um Stammzellforschung, Klonen und Reproduktionstechnologien wurden in Deutschland weitgehend im nationalstaatlichen Rahmen und mit Blick auf Entwicklungen im angelsächsischen Raum geführt. Dabei sind diese Forschungsrichtungen und Technologien kein genuin „westliches“ Phänomen – immerhin wurde das erste Retortenkind in Polen bereits 1987 geboren. Heidi Hofmann lässt in ihrem Band polnische Philosoph/-innen, Jurist/-innen und Politikerinnen zu Wort kommen und öffnet den Blick dafür, dass die Art und Weise, in der Reproduktionstechnologien gesellschaftlich problematisiert werden, in Polen durch ganz andere politische, kulturelle und historische Konstellationen geprägt ist als in Deutschland.

  1. Restaurierung von Seen und Renaturierung von Seeufern (United States)

    Grüneberg, Björn; Ostendorp, Wolfgang; Leßmann, Dieter; Wauer, Gerlinde; Nixdorf, Brigitte

    Süßwasserseen haben als ökosysteme und Lebensraum für Pflanzen und Tiere eine herausragende Bedeutung für die Artenvielfalt auf der Erde und prägen als Landschaftselemente unsere natürliche Umwelt. Seen fungieren als natürliche Stoffsenken, vor allem für Kohlenstoff und Nährstoffe, aber auch als Senken für in ihren Einzugsgebieten emittierte gelöste und feste Schadstoffe. Darüber hinaus ist Wasser eine wichtige Naturressource. Süßwasserseen stellen in den meisten Regionen der Erde lebenswichtige Quellen für die Versorgung mit Trinkwasser und tierischem Eiweiß (Fischfang) dar. Sie dienen als Wasserspeicher für die landwirtschaftliche und industrielle Nutzung. Auch für Erholungsaktivitäten des Menschen kommt ihnen eine große Bedeutung zu.

  2. Long-term remission in BCR/ABL-positive AML-M6 patient treated with Imatinib Mesylate. (United States)

    Pompetti, Franca; Spadano, Antonio; Sau, Antonella; Mennucci, Antonio; Russo, Rosa; Catinella, Virginia; Franchi, Paolo Guanciali; Calabrese, Giuseppe; Palka, Giandomenico; Fioritoni, Giuseppe; Iacone, Antonio


    BCR/ABL-positive acute myeloid leukemia (AML) is a rare disease, characterized by a poor prognosis, with resistance to induction chemotherapy and frequent relapses in responsive patients. Here we report a case of BCR/ABL-positive AML-M6 who, after relapse, was treated with Imatinib Mesylate (600 mg/die) and within 4 months achieved a cytogenetic and molecular complete response. After more than 4 years of continuous Imatinib therapy, nested RT-PCR for BCR/ABL is persistently negative. The case reported shows that the response obtained with Imatinib Mesylate in BCR/ABL-positive AML may be long lasting, offering a chance of successful treatment for this poor prognosis group of patients.

  3. E-Government und E-Banking: Aktueller Stand, Evaluation und Erfolgsfaktoren


    Bayer, Tobias


    Zu Max Webers Zeiten entsprach die Bürokratie noch ganz dem Vorbild des preussischen Militärs " klare Hierarchien und klare Aufgabenbereiche schlugen sich nieder in Effizienz und Effektivität. Heute ist das Bild getrübt und Worte wie "Erstarrung", "Überreglementierung" und "Verwaltungskultur" machen die Runde. Neben den gestiegenen Erwartungen der Bürger, die sich in Zeiten des E-Banking und E-Commerce nicht mehr in lange Warteschlangen einreihen wollen und auf die rigiden Öffnungszeiten der ...

  4. Cellular intrinsic mechanism affecting the outcome of AML treated with Ara-C in a syngeneic mouse model.

    Directory of Open Access Journals (Sweden)

    Wenjun Zhao

    Full Text Available The mechanisms underlying acute myeloid leukemia (AML treatment failure are not clear. Here, we established a mouse model of AML by syngeneic transplantation of BXH-2 derived myeloid leukemic cells and developed an efficacious Ara-C-based regimen for treatment of these mice. We proved that leukemic cell load was correlated with survival. We also demonstrated that the susceptibility of leukemia cells to Ara-C could significantly affect the survival. To examine the molecular alterations in cells with different sensitivity, genome-wide expression of the leukemic cells was profiled, revealing that overall 366 and 212 genes became upregulated or downregulated, respectively, in the resistant cells. Many of these genes are involved in the regulation of cell cycle, cellular proliferation, and apoptosis. Some of them were further validated by quantitative PCR. Interestingly, the Ara-C resistant cells retained the sensitivity to ABT-737, an inhibitor of anti-apoptosis proteins, and treatment with ABT-737 prolonged the life span of mice engrafted with resistant cells. These results suggest that leukemic load and intrinsic cellular resistance can affect the outcome of AML treated with Ara-C. Incorporation of apoptosis inhibitors, such as ABT-737, into traditional cytotoxic regimens merits consideration for the treatment of AML in a subset of patients with resistance to Ara-C. This work provided direct in vivo evidence that leukemic load and intrinsic cellular resistance can affect the outcome of AML treated with Ara-C, suggesting that incorporation of apoptosis inhibitors into traditional cytotoxic regimens merits consideration for the treatment of AML in a subset of patients with resistance to Ara-C.

  5. An AML1-ETO/miR-29b-1 regulatory circuit modulates phenotypic properties of acute myeloid leukemia cells. (United States)

    Zaidi, Sayyed K; Perez, Andrew W; White, Elizabeth S; Lian, Jane B; Stein, Janet L; Stein, Gary S


    Acute myeloid leukemia (AML) is characterized by an aggressive clinical course and frequent cytogenetic abnormalities that include specific chromosomal translocations. The 8;21 chromosomal rearrangement disrupts the key hematopoietic RUNX1 transcription factor, and contributes to leukemia through recruitment of co-repressor complexes to RUNX1 target genes, altered subnuclear localization, and deregulation of the myeloid gene regulatory program. However, a role of non-coding microRNAs (miRs) in t(8;21)-mediated leukemogenesis is minimally understood. We present evidence of an interplay between the tumor suppressor miR-29b-1 and the AML1-ETO (also designated RUNX1-RUNX1T1) oncogene that is encoded by the t(8;21). We find that AML1-ETO and corepressor NCoR co-occupy the miR-29a/b-1 locus and downregulate its expression in leukemia cells. Conversely, re-introduction of miR-29b-1 in leukemia cells expressing AML1-ETO causes significant downregulation at the protein level through direct targeting of the 3' untranslated region of the chimeric transcript. Restoration of miR-29b-1 expression in leukemia cells results in decreased cell growth and increased apoptosis. The AML1-ETO-dependent differentiation block and transcriptional program are partially reversed by miR-29b-1. Our findings establish a novel regulatory circuit between the tumor-suppressive miR-29b-1 and the oncogenic AML1-ETO that controls the leukemic phenotype in t(8;21)-carrying acute myeloid leukemia.

  6. Hif-1α and Hif-2α synergize to suppress AML development but are dispensable for disease maintenance. (United States)

    Vukovic, Milica; Guitart, Amelie V; Sepulveda, Catarina; Villacreces, Arnaud; O'Duibhir, Eoghan; Panagopoulou, Theano I; Ivens, Alasdair; Menendez-Gonzalez, Juan; Iglesias, Juan Manuel; Allen, Lewis; Glykofrydis, Fokion; Subramani, Chithra; Armesilla-Diaz, Alejandro; Post, Annemarie E M; Schaak, Katrin; Gezer, Deniz; So, Chi Wai Eric; Holyoake, Tessa L; Wood, Andrew; O'Carroll, Dónal; Ratcliffe, Peter J; Kranc, Kamil R


    Leukemogenesis occurs under hypoxic conditions within the bone marrow (BM). Knockdown of key mediators of cellular responses to hypoxia with shRNA, namely hypoxia-inducible factor-1α (HIF-1α) or HIF-2α, in human acute myeloid leukemia (AML) samples results in their apoptosis and inability to engraft, implicating HIF-1α or HIF-2α as therapeutic targets. However, genetic deletion of Hif-1α has no effect on mouse AML maintenance and may accelerate disease development. Here, we report the impact of conditional genetic deletion of Hif-2α or both Hif-1α and Hif-2α at different stages of leukemogenesis in mice. Deletion of Hif-2α accelerates development of leukemic stem cells (LSCs) and shortens AML latency initiated by Mll-AF9 and its downstream effectors Meis1 and Hoxa9. Notably, the accelerated initiation of AML caused by Hif-2α deletion is further potentiated by Hif-1α codeletion. However, established LSCs lacking Hif-2α or both Hif-1α and Hif-2α propagate AML with the same latency as wild-type LSCs. Furthermore, pharmacological inhibition of the HIF pathway or HIF-2α knockout using the lentiviral CRISPR-Cas9 system in human established leukemic cells with MLL-AF9 translocation have no impact on their functions. We therefore conclude that although Hif-1α and Hif-2α synergize to suppress the development of AML, they are not required for LSC maintenance. © 2015 Vukovic et al.

  7. Personen- und Güterverkehr (United States)

    Flämig, Heike; Gertz, Carsten; Mühlhausen, Thorsten

    Im Jahr 2010 war in Deutschland der Verkehrssektor für fast 20 % der energiebedingten Treibhausgase verantwortlich. Das Klima hat sich bereits so weit verändert, dass zur Sicherung der Funktion der Verkehrssysteme auch Anpassungsmaßnahmen notwendig sind. Diese Maßnahmen müssen durch verkehrsreduzierende bzw. -beeinflussende Maßnahmen ergänzt werden. Ausgehend von den Emissionen im Verkehrssektor und möglichen Minderungen schlägt das Kapitel den Bogen zu Optionen der Anpassung an den Klimawandel, die ausführlich und konkret dargestellt werden. Besonders betrachtet werden die mannigfaltigen Gefahren der Rückkopplung sowie die vielfältigen Wechselwirungen mit anderen Themengebieten und Sektoren.

  8. Osteoporose und Genetik des Knochenstoffwechsels

    Directory of Open Access Journals (Sweden)

    Obermayer-Pietsch B


    Full Text Available Osteoporose ist in hohem Maß genetisch determiniert. Neue Wege der molekularbiologischen Forschung haben sich in den letzten Jahren auf diesem Gebiet etabliert. "Gene mapping" mit polymorphen genetischen Markern auf der Suche nach Phänotyp-assoziierten Genen ist ein aufwendiges, aber vielversprechendes Verfahren und wird durch die Erkenntnisse des Human Genome Projects beschleunigt. So wurde jüngst u. a. das Low-density Lipoprotein 5-Gen als wichtig für den Knochenstoffwechsel identifiziert. Kandidaten-gene wie Hormonrezeptor-, Cytokin- oder Kollagen-Gene werden hinsichtlich ihrer Gen-Gen- und Gen-Umwelt- Interaktionen untersucht und erlauben neue funktionelle Einsichten in Erkrankungen des Knochenstoffwechsels. Mutationen der Kollagen-Gene sind bei einigen seltenen Erkrankungen, wie dem Osteoporose-Pseudogliom-Syndrom oder der Osteogenesis imperfecta gefunden worden, könnten aber auch für häufige Varianten von Bindegewebsstörungen wie der congenitalen Hüftdysplasie verantwortlich sein, die etwa 10 % der weiblichen kaukasischen Bevölkerung in unterschiedlichem Ausmaß betrifft. Osteoporose am Schenkelhals und erhöhte Gelenkslaxizität sowie andere generalisierte Veränderungen des Knochen- und Kollagenstoffwechsels können hier möglicherweise ebenfalls durch Störungen des Kollagen I alpha 1-Gens erklärt werden. In Summe können wir zahlreiche neue Einsichten in die Pathophysiologie des Skelettsystems erwarten, die uns auch neue Zugangswege für Diagnostik und Therapie unserer Patienten ermöglichen werden.

  9. CLILiG und Musikunterricht

    Directory of Open Access Journals (Sweden)

    Merle Jung


    Full Text Available Der Einsatz von Musik und Liedern im Sprachunterricht ist seit der Entwicklung der kommunikativen Methoden ein beliebtes Thema in der Fremdsprachendidaktik. Musik und Sprache haben Ähnlichkeiten bei den kognitiven Verarbeitungsprozessen und der gedächtnisstützende Einfluss der Musik und ihr Nutzen für das Sprachenlernen sind allgemein bekannt. Dieser Nutzen wird aber meistens nur aus der (fremdsprachlichen Perspektive gezogen, die musikalische Erziehung der Lernenden bleibt im Hintergrund. Dabei bietet der bilinguale Musikunterricht mit der klaren Ausrichtung auf die musikalischen Ziele eine gute Möglichkeit, diese zwei Bereiche – Musik und Sprache – gleichwertig miteinander zu verbinden. Das Ziel des vorliegenden Beitrags ist es, die Vorteile des bilingualen Musikunterrichts zu erörtern und an einem Beispielmodul zum Thema Wetter im Herbst zu verdeutlichen. The use of music and songs in language teaching has been a popular topic in foreign language didactics since the development of communicative methods. Music and language have similarities in cognitive processing and the memory supporting influence of music and its beneficial effect on language learning are generally known. However, this benefit will usually be drawn only from the (foreign language perspective, the musical education of the learners remains in the background. Yet bilingual music education with a clear focus on the musical goals provides a great opportunity to connect these two areas - music and language - equally to each other. The aim of this paper is to discuss the advantages of bilingual music education and to present an example based on the bilingual module Weather in Autumn.

  10. Strategische Beschaffung: Grundlagen, Planung und Umsetzung eines integrierten Supply Management

    NARCIS (Netherlands)

    van Weele, A.J.; Eßig, M.


    Dieses Buch bietet – erstmalig in deutscher Übersetzung – eine umfassende und sehr anschauliche Darstellung zu Grundlagen, Planung und Umsetzung einer modernen Beschaffungsfunktion. Beschaffung und Supply Management werden dabei als wesentliches Bindeglied innerhalb des Managementsystems eines

  11. Theoriebedingte Wörterbuchform- probleme und wörterbuch ...

    African Journals Online (AJOL)

    zunehmend mehr neue Elemente der Wörterbuchform im Vorspann, im Wörterverzeichnis und im. Nachspann ...... tur und -architektur aufweisen und sich nur quantitativ bei den überdachten ...... modernen Printwörterbüchern. Lexikos 18: ...

  12. Emil Fahrenkamp : Bauten und Projekte für Berlin

    NARCIS (Netherlands)

    Jacob, B.


    Thema der vorliegenden Arbeit ist die umfassende Aufarbeitung und Dokumentation der Bauten und Projekte Emil Fahrenkamps (*1885, 1966) in Berlin und Potsdam-Babelsberg sowie die kritische Einordnung seiner Arbeiten in den Kontext der Baugeschichte des 20. Jahrhunderts. Den zentralen

  13. [Preussen und Livland im Zeichen der Reformation] / Anti Selart

    Index Scriptorium Estoniae

    Selart, Anti, 1973-


    Arvustus: Preussen und Livland im Zeichen der Reformation. Hrsg. von Arno Mentzel-Reuters und Klaus Neitmann. (Tagungsberichte der Historischen Kommission für ost- und westpreussische Landesforschung, 28). Fibre Verlag. Osnabrück 2014

  14. Comprehensive mapping of the effects of azacitidine on DNA methylation, repressive/permissive histone marks and gene expression in primary cells from patients with MDS and MDS-related disease. (United States)

    Tobiasson, Magnus; Abdulkadir, Hani; Lennartsson, Andreas; Katayama, Shintaro; Marabita, Francesco; De Paepe, Ayla; Karimi, Mohsen; Krjutskov, Kaarel; Einarsdottir, Elisabet; Grövdal, Michael; Jansson, Monika; Ben Azenkoud, Asmaa; Corddedu, Lina; Lehmann, Sören; Ekwall, Karl; Kere, Juha; Hellström-Lindberg, Eva; Ungerstedt, Johanna


    Azacitidine (Aza) is first-line treatment for patients with high-risk myelodysplastic syndromes (MDS), although its precise mechanism of action is unknown. We performed the first study to globally evaluate the epigenetic effects of Aza on MDS bone marrow progenitor cells assessing gene expression (RNA seq), DNA methylation (Illumina 450k) and the histone modifications H3K18ac and H3K9me3 (ChIP seq). Aza induced a general increase in gene expression with 924 significantly upregulated genes but this increase showed no correlation with changes in DNA methylation or H3K18ac, and only a weak association with changes in H3K9me3. Interestingly, we observed activation of transcripts containing 15 endogenous retroviruses (ERVs) confirming previous cell line studies. DNA methylation decreased moderately in 99% of all genes, with a median β-value reduction of 0.018; the most pronounced effects seen in heterochromatin. Aza-induced hypomethylation correlated significantly with change in H3K9me3. The pattern of H3K18ac and H3K9me3 displayed large differences between patients and healthy controls without any consistent pattern induced by Aza. We conclude that the marked induction of gene expression only partly could be explained by epigenetic changes, and propose that activation of ERVs may contribute to the clinical effects of Aza in MDS.

  15. [Geisteswissenschaft und Publizistik im Baltikum des 19. und frühen 20. Jahrhunderts] / Manfred von Boetticher

    Index Scriptorium Estoniae

    Boetticher, Manfred von, 1947-


    Arvustus: Geisteswissenschaft und Publizistik im Baltikum des 19. und frühen 20. Jahrhunderts (Schriften der Baltischen Historischen Kommission, 17; Baltische Biographische Forschungen, 1). Hrsg. von Norbert Angermann, Wilhelm Lenz und Konrad Maier. (Berlin: LIT-Varlag, 2011)

  16. Renal, gastrointestinal, and hepatic late effects in survivors of childhood acute myeloid leukemia treated with chemotherapy only--a NOPHO-AML study

    DEFF Research Database (Denmark)

    Skou, Anne-Sofie; Glosli, Heidi; Jahnukainen, Kirsi


    BACKGROUND: We investigated the spectrum, frequency, and risk factors for renal, gastrointestinal, and hepatic late adverse effects in survivors of childhood acute myeloid leukemia (AML) without relapse treated with chemotherapy alone according to three consecutive AML trials by the Nordic Society...

  17. Functionally deregulated AML1/RUNX1 cooperates with BCR-ABL to induce a blastic phase-like phenotype of chronic myelogenous leukemia in mice.

    Directory of Open Access Journals (Sweden)

    Kiyoko Yamamoto

    Full Text Available Patients in the chronic phase (CP of chronic myelogenous leukemia (CML have been treated successfully following the advent of ABL kinase inhibitors, but once they progress to the blast crisis (BC phase the prognosis becomes dismal. Although mechanisms underlying the progression are largely unknown, recent studies revealed the presence of alterations of key molecules for hematopoiesis, such as AML1/RUNX1. Our analysis of 13 BC cases revealed that three cases had AML1 mutations and the transcript levels of wild-type (wt. AML1 were elevated in BC compared with CP. Functional analysis of representative AML1 mutants using mouse hematopoietic cells revealed the possible contribution of some, but not all, mutants for the BC-phenotype. Specifically, K83Q and R139G, but neither R80C nor D171N mutants, conferred upon BCR-ABL-expressing cells a growth advantage over BCR-ABL-alone control cells in cytokine-free culture, and the cells thus grown killed mice upon intravenous transfer. Unexpectedly, wt.AML1 behaved similarly to K83Q and R139G mutants. In a bone marrow transplantation assay, K83Q and wt.AML1s induced the emergence of blast-like cells. The overall findings suggest the roles of altered functions of AML1 imposed by some, but not all, mutants, and the elevated expression of wt.AML1 for the disease progression of CML.

  18. The impact of TEL-AML1 (ETV6-RUNX1) expression in precursor B cells and implications for leukaemia using three different genome-wide screening methods

    International Nuclear Information System (INIS)

    Linka, Y; Ginzel, S; Krüger, M; Novosel, A; Gombert, M; Kremmer, E; Harbott, J; Thiele, R; Borkhardt, A; Landgraf, P


    The reciprocal translocation t(12;21)(p13;q22), the most common structural genomic alteration in B-cell precursor acute lymphoblastic leukaemia in children, results in a chimeric transcription factor TEL-AML1 (ETV6-RUNX1). We identified directly and indirectly regulated target genes utilizing an inducible TEL-AML1 system derived from the murine pro B-cell line BA/F3 and a monoclonal antibody directed against TEL-AML1. By integration of promoter binding identified with chromatin immunoprecipitation (ChIP)-on-chip, gene expression and protein output through microarray technology and stable labelling of amino acids in cell culture, we identified 217 directly and 118 indirectly regulated targets of the TEL-AML1 fusion protein. Directly, but not indirectly, regulated promoters were enriched in AML1-binding sites. The majority of promoter regions were specific for the fusion protein and not bound by native AML1 or TEL. Comparison with gene expression profiles from TEL-AML1-positive patients identified 56 concordantly misregulated genes with negative effects on proliferation and cellular transport mechanisms and positive effects on cellular migration, and stress responses including immunological responses. In summary, this work for the first time gives a comprehensive insight into how TEL-AML1 expression may directly and indirectly contribute to alter cells to become prone for leukemic transformation

  19. Investigation of porosity and fractal properties of the sintered metal and semiconductor layers in the MDS capacitor structure

    Directory of Open Access Journals (Sweden)

    Skatkov Leonid


    Full Text Available MDS capacitor (metal - dielectric - semiconductor is a structure in which metal plate is represented by compact bulk-porous pellets of niobium sintered powder, and semiconductor plate - by pyrolytic layer of MnO2. In the present paper we report the results of investigation of microporosity of sintered Nb and pyrolytic MnO2 and also the fractal properties of semiconductor layer.

  20. Entwicklung und Anwendung neuer NMR-Methoden: Orientierungsmedien zur Strukturbestimmung mit anisotropen Parametern und Metabonomics


    Büchler, Silke


    Das Ziel dieser Arbeit war die Entwicklung und Anwendung neuer Orientierungsmedien zur Strukturbestimmung mit anisotropen Parametern, sowie die Etablierung von Metabonomics-Studien an Flüssigzellkulturen und Reispflanzen.

  1. Klimaanpassung in Land- und Forstwirtschaft: Ergebnisse eines Workshops der Ressortforschungsinstitute FLI, JKI und Thünen-Institut


    Schimmelpfennig, Sonja; Heidecke, Claudia; Beer, Holger; Bittner, Florian; Klages, Susanne; Krengel, Sandra; Lange, Stefan


    Das Working Paper stellt die Ergebnisse einer Umfrage und eines Workshops zusammen, die von Wissenschaftlern und Wissenschaftlerinnen der Ressortforschungsinstitute Thünen-Institut, Julius Kühn-Institut (JKI) und Friedrich-Loeffler-Institut (FLI) im Herbst 2016 zusammengetragen und diskutiert worden sind. Ziel des Workshops und der Umfrage war, den Stand des Wissens zu Klimaanpassungsthemen in der Ressortforschung des BMEL und die zukünftigen Herausforderungen einer Anpassung an den Klimawand...

  2. T-cell receptor Vbeta CDR3 oligoclonality frequently occurs in childhood refractory cytopenia (MDS-RC) and severe aplastic anemia

    DEFF Research Database (Denmark)

    Vries, A.C. de; Langerak, A.W.; Verhaaf, B.


    (Very) severe acquired aplastic anemia ((v)SAA) and myelodysplastic syndrome (MDS) are rare diseases in childhood. (V)SAA is a bone marrow (BM) failure syndrome characterized by immune-mediated destruction of hematopoietic progenitors. MDS is a malignant clonal stem cell disorder, of which...... the hypoplastic variant is, in case of absence of a cytogenetic clone, difficult to separate from (v)SAA. Recently, studies provided a molecular signature of autoimmunity in adult (v)SAA, by showing oligoclonality based on the length of the TCR Vbeta CDR3 region. We investigated retrospectively the frequency...... and the discriminative value of TCR Vbeta CDR3 oligoclonality in pediatric (v)SAA and MDS patients. Peripheral blood (PB) and/or BM mononuclear cell samples of pediatric patients with (v)SAA (n=38), refractory cytopenia (MDS-RC) (n=28) and 18 controls were analysed via TCR Vbeta heteroduplex PCR analysis of extracted...

  3. Geschmackspapillendichte und Geschmackswahrnehmung bei Jugendlichen mit Essstörungen und einer gesunden Kontrollgruppe


    Kaltenhofer, Alice


    Fragestellung Die Schmeckwahrnehmung wird u.a. über Lernprozesse, kognitive Vorgänge, genetische und biochemische Faktoren reguliert. Ess- und Diätverhalten werden durch sie beeinflusst. Den anatomisch und physiologisch ersten Abschnitt der Schmeckwahrnehmung bilden die fungiformen Geschmackspapillen. In den Geschmackspapillen liegen die Geschmacksknopsen, mit deren Hilfe die Schmeckstoffe aufgenommen und in Form von Aktionspotentialen zum Thalamus, dem limbischen System,dem Gyrus postzentral...

  4. Kontrolle des Verwaltungsrates : eine Untersuchung der internen und externen Kontrollinstitutionen, -instrumente und -mechanismen


    Reust, Dominik


    Eine wichtige Erkenntnis dieser Arbeit ist, dass eine effiziente und effektive Kontrolle des Verwaltungsrates nur über das Zusammenspiel der internen körperschaftlichen Kontrollinstitutionen und -instrumente mit den externen Kontrollinstitutionen und Kontrollmechanismen des Marktes erreicht wird. Die Vorschriften der VegüV betreffend transparente Entschädigungspolitik und unabhängige Stimmrechtsvertreter sowie die in der Aktienrechtsrevision angestrebte Stärkung der Informations-, Mitwirk...

  5. Recht und Rechtssystem als globale Struktur und Medium der Verhaltensorientierung / Raul Narits

    Index Scriptorium Estoniae

    Narits, Raul, 1952-


    Äratr.: Multiple Modernität, Globalisierung der Rechtsordnung und Kommunikationsstruktur der Rechtssysteme : Internationales Symposium zur Theorie der Rechtskommunikation an der Universität Tartu im April 2006 ; II. Sonderheft Estland. Berlin, 2008, lk. 219-238. - (Rechtstheorie : Zeitschrift für Logik und Juristische Methodenlehre, Rechtsinformatik, Kommunikationsforschung, Normen- und Handlungstheorie, Soziologie und Philosophie des Rechts ; Bd. 38, 2007, H. 2/3)

  6. Das Sabbatjahr für Lehrerinnen und Lehrer: Wer profitiert und in welcher Form?


    Rothland, Martin


    Das Sabbatjahr für Lehrerinnen und Lehrer wird programmatisch als Maßnahme der Belastungsreduktion, der Regeneration sowie der Ressourcenstärkung diskutiert. Empirische Belege für die erwarteten Effekte finden sich jedoch kaum. Im Rahmen einer Längsschnittstudie mit drei Erhebungszeitpunkten vor, während und nach dem Sabbatjahr werden die Entwicklung der Belastungswahrnehmung, des Gesundheitszustands und allgemeiner sowie arbeitsbezogener Emotionen (Berufs- und Lebenszufriedenheit) auf der Ba...

  7. Referenzmodelle im Mobile Business: Analyse und Entwicklung neuer Rollen, Szenarien und Geschäftsmodelle


    Hufenbach, Yvonne


    Das digitale Zeitalter ist charakterisiert durch sich stetig wandelnde Märkte, Techniken und wirtschaftliche Voraussetzungen. Klassische Wertschöpfungsketten brechen auf und wandeln sich zu Wertschöpfungsnetzen. Dabei findet eine Neuzuordnung zwischen Wertschöpfungstätigkeiten und Marktteilnehmern statt. Diese digitale Welt ist zudem durch hohe Interdependenzen wirtschaftlicher, informationstechnischer und rechtlicher Fragestellungen gekennzeichnet. Vor diesem Hintergrund verfolgt die Arb...

  8. Arbeitszeitflexibilisierung in der westdeutschen Metall- und Elektroindustrie und die Verbandsstrategien - Eine vergleichende Analyse der arbeitszeitpolitischen Strategien des Arbeitgeberverbandes Gesamtmetall und der Industriegewerkschaft Metall


    Altun, Ufuk


    Arbeitszeitpolitik und Arbeitszeitgestaltung haben seit dem Tarifkompromiss im Jahre 1984 in der Metall-, und Elektroindustrie in der politischen und wissenschaftlichen Diskussion einen immensen Bedeutungszuwachs erfahren. Die Forderungen nach einer flexibleren Arbeitszeitgestaltung haben zeitgleich sowohl aus der Globalisierungsdiskussion und der Debatte um die Wettbewerbsfähigkeit des "Wirtschaftsstandorts Deutschland" heraus wie auch aus beschäftigungspolitischen Gründen neuen Auftrieb bek...

  9. MRD in AML: it is time to change the definition of remission. (United States)

    Ossenkoppele, Gert J; Schuurhuis, Gerrit Jan


    The possibility of defining residual disease far below the morphological level of 5% blast cells is changing the landscape of risk classification in acute myeloid leukemia (AML). The so-called minimal residual disease (MRD) approach at this time can establish the presence of leukemia cells down to levels of 1:1000-1:10(6) white blood cells, compared to 1:20 for morphology. Availability of the newer and more sensitive technology to quantify the level of leukemic burden raises the issue of whether MRD should emerge as a new definition of complete response. This paper explores some of the issues surrounding such a change in definition. Copyright © 2014 Elsevier Ltd. All rights reserved.

  10. Osteopetrose - aktuelle Diagnostik und Therapie

    Directory of Open Access Journals (Sweden)

    Schulz AS


    Full Text Available Unter dem Begriff Osteopetrose wird eine heterogene Gruppe von Krankheiten zusammengefasst, die durch eine pathologisch vermehrte Knochenmasse charakterisiert ist. Diese Osteosklerose basiert in den meisten Fällen auf einem Defekt in der Knochenresorption durch Osteoklasten. Beim Menschen können mehrere Typen unterschieden und nach dem Vererbungsmodus, dem Manifestationsalter, der Schwere der klinischen Symptomatik und nach assoziierten Symptomen klassifiziert werden. Hauptformen sind die infantile "maligne" autosomal rezessive Osteopetrose (ARO, intermediäre autosomal rezessive Formen (IARO und milder verlaufende autosomal dominante Subtypen (ADO. In den letzten Jahren konnten mehrere zur Osteopetrose führende Genveränderungen identifiziert werden. Alle diese Genveränderungen bei humaner Osteopetrose betreffen Proteine, die an der Differenzierung oder Funktion der Osteoklasten beteiligt sind. Da die Osteoklasten sich aus der hämatopoietischen Stammzelle differenzieren, ist die hämatopoietische Stammzelltransplantation eine kurative Therapieoption bei schweren Osteopetroseformen. Allerdings ist diese Therapie mit erheblichen Risiken verbunden. Darüber hinaus sind bestimmte Subtypen der Osteopetrose mit schweren neurologischen Veränderungen assoziiert, die durch eine Stammzelltransplantation nicht positiv beeinflusst werden können. Ein genaues Verständnis der Pathogenese der humanen Osteopetrose ist daher wichtig für die Wahl der richtigen Therapie und gewährt darüber hinaus einen tieferen Einblick in die Physiologie and andere Pathologien des Knochens.

  11. Natur und Moderne um 1900

    DEFF Research Database (Denmark)

    , nordeuropäischen Vergleich widmen sich die Beiträge den medialen Repräsentationen von Natur (in Literatur, Philosophie, Film, Foto) ebenso wie der Kolonisierung des Raumes (in Tourismus, Reisen, Sport, Natur- und Heimatschutz). Der Band bietet damit auch Impulse für die neuen theoretisch-methodischen Ansätze der...

  12. Low-dose total body irradiation and G-CSF without hematopoietic stem cell support in the treatment of relapsed or refractory acute myelogenous leukemia (AML), or AML in second or subsequent remission

    International Nuclear Information System (INIS)

    Shulman, Lawrence N.; Tarbell, Nancy J.; Storen, Elizabeth; Marcus, Karen; Mauch, Peter M.


    Purpose: Patients with relapsed acute myelogenous leukemia (AML), who are not eligible for bone marrow transplantation, have a poor prognosis when treated with chemotherapy alone. Total body irradiation (TBI) is an effective modality against AML when used in doses of 1000-1400 cGy with hematopoietic stem cell support. We undertook a phase I study of TBI with granulocyte-colony-stimulating factor (G-CSF) support, without stem cell support in patients with AML either in relapse or second or subsequent remission. Methods and Materials: Patients with relapsed AML, or AML in second or subsequent remission were treated in a phase I study of TBI followed by G-CSF. The first dose level was 200 cGy. After the initial cohort of patients it was clear that patients with overt leukemia did not benefit from this treatment, and subsequent patients were required to be in remission at the time of TBI. Results: Eleven patients were treated, 4 in overt relapse, and 7 in remission. 200 cGy was used in all, and dose escalation was not possible due to prolonged thrombocytopenia in all patients but one. Neutrophil recovery was adequate in those patients who remained in remission after TBI. Patients with overt leukemia had transient reduction in blast counts, but rapid recurrence of their leukemia. Patients treated in remission had short remissions, with the exception of one patient who is in remission 32 months after treatment. Conclusion: There is some antileukemic effect of TBI even at 200 cGy, though this dose appears to be too low to help a significant number of patients. If TBI is to be escalated without stem cell support, then a thrombopoietic agent will need to be used

  13. Circumvention of ara-C resistance by aphidicolin in blast cells from patients with AML. (United States)

    Sargent, J M; Elgie, A W; Williamson, C J; Lewandowicz, G M; Taylor, C G


    Treatment failure in AML is often attributed to P-glycoprotein-associated multidrug resistance. However, the importance of increased DNA repair in resistant cells is becoming more apparent. In order to investigate the ability of the DNA repair inhibitor aphidicolin to modulate drug resistance, we continually exposed blasts cells, isolated from 22 patients with AML, to a variety of agents +/- 15 microM aphidicolin for 48 hours. Cell survival was measured using the MTT assay. Overall, there was no significant effect of aphidicolin on sensitivity to daunorubicin, doxorubicin, etoposide or fludarabine. However, there was a marked increase in sensitivity to ara-C with a median 4.75-fold increase overall (range 0.8-80-fold;P< 0.005). The effect of aphidicolin was significantly greater in blast cells found resistant in vitro to ara-C (8.9-fold compared to 2.12-fold, P< 0.01). This observation was further validated by the correlation between ara-C LC(50)and extent of modulation effect (P< 0.05). Cells isolated from 10 cord blood samples were also tested in order to establish the haematological toxicity of combining ara-C and aphidicolin. The therapeutic index (LC(50)normal cells/tumour cells) for ara-C + aphidicolin was higher than that for ara-C alone suggesting no increased myelotoxicity for the combination. Increased cytotoxicity without increased haematotoxicity makes the combination of ara-C plus aphidicolin ideal for inclusion in future clinical trials. Copyright 2001 Cancer Research Campaign.

  14. Relationship between the non-motor items of the MDS-UPDRS and Quality of Life in patients with Parkinson's disease. (United States)

    Skorvanek, Matej; Rosenberger, Jaroslav; Minar, Michal; Grofik, Milan; Han, Vladimir; Groothoff, Johan W; Valkovic, Peter; Gdovinova, Zuzana; van Dijk, Jitse P


    The Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) is a newly developed comprehensive tool to assess Parkinson's disease (PD), which covers a wider range of non-motor PD manifestations than the original UPDRS scale. The aim of this study was to assess the relationship between the MDS-UPDRS and Quality of Life (QoL) and to analyze the relationship between individual MDS-UPDRS non-motor items and QoL. A total of 291 PD patients were examined in a multicenter Slovak study. Patients were assessed by the MDS-UPDRS, HY scale and PDQ39. Data were analyzed using the multiple regression analyses. The mean participant age was 68.0 ± 9.0 years, 53.5% were men, mean disease duration was 8.3 ± 5.3 years and mean HY was 2.7 ± 1.0. In a multiple regression analysis model the PDQ39 summary index was related to MDS-UPDRS parts II, I and IV respectively, but not to part III. Individual MDS-UPDRS non-motor items related to the PDQ39 summary index in the summary group and in the non-fluctuating patients subgroup were pain, fatigue and features of dopamine dysregulation syndrome (DDS). In the fluctuating PD patient subgroup, PDQ39 was related to pain and Depressed mood items. Other MDS-UPDRS non-motor items e.g. Anxious mood, Apathy, Cognitive impairment, Hallucinations and psychosis, Sleep problems, Daytime sleepiness and Urinary problems were related to some PDQ39 domains. The overall burden of NMS in PD is more important in terms of QoL than motor symptoms. Individual MDS-UPDRS non-motor items related to worse QoL are especially pain and other sensations, fatigue and features of DDS. Copyright © 2015 Elsevier B.V. All rights reserved.

  15. In vitro-Permeationsstudien von hydrophilen und lipophilen Arzneistoffen an okularen Geweben und Zellkulturen


    Scholz, Martina


    Da die Arzneistoffpermeation durch okulare Gewebe einen entscheidenden Einfluss auf die Heilung vieler Augenleiden hat, wurde die in vitro-Permeation hydrophiler und lipophiler Arzneistoffe durch okulare Gewebe und Zellkulturen in dieser Arbeit untersucht. Die Dissertation befasst sich vorrangig mit der Permeation des hydrophilen Modellarzneistoffs Pilocarpinhydrochlorid (P-HCl) durch isolierte Schweinecornea (SC), Schweinesklera, Kaninchenkonjunktiva und corneale bzw. konjunktivale Kan...

  16. ERG and FLI1 binding sites demarcate targets for aberrant epigenetic regulation by AML1-ETO in acute myeloid leukemia

    NARCIS (Netherlands)

    Martens, Joost H. A.; Mandoli, Amit; Simmer, Femke; Wierenga, Bart-Jan; Saeed, Sadia; Singh, Abhishek A.; Altucci, Lucia; Vellenga, Edo; Stunnenberg, Hendrik G.


    ERG and FLI1 are closely related members of the ETS family of transcription factors and have been identified as essential factors for the function and maintenance of normal hematopoietic stem cells. Here genome-wide analysis revealed that both ERG and FLI1 occupy similar genomic regions as AML1-ETO

  17. Calreticulin exposure by malignant blasts correlates with robust anticancer immunity and improved clinical outcome in AML patients (United States)

    Fucikova, Jitka; Truxova, Iva; Hensler, Michal; Becht, Etienne; Kasikova, Lenka; Moserova, Irena; Vosahlikova, Sarka; Klouckova, Jana; Church, Sarah E.; Cremer, Isabelle; Kepp, Oliver; Kroemer, Guido; Galluzzi, Lorenzo; Salek, Cyril


    Cancer cell death can be perceived as immunogenic by the host only when malignant cells emit immunostimulatory signals (so-called “damage-associated molecular patterns,” DAMPs), as they die in the context of failing adaptive responses to stress. Accumulating preclinical and clinical evidence indicates that the capacity of immunogenic cell death to (re-)activate an anticancer immune response is key to the success of various chemo- and radiotherapeutic regimens. Malignant blasts from patients with acute myeloid leukemia (AML) exposed multiple DAMPs, including calreticulin (CRT), heat-shock protein 70 (HSP70), and HSP90 on their plasma membrane irrespective of treatment. In these patients, high levels of surface-exposed CRT correlated with an increased proportion of natural killer cells and effector memory CD4+ and CD8+ T cells in the periphery. Moreover, CRT exposure on the plasma membrane of malignant blasts positively correlated with the frequency of circulating T cells specific for leukemia-associated antigens, indicating that ecto-CRT favors the initiation of anticancer immunity in patients with AML. Finally, although the levels of ecto-HSP70, ecto-HSP90, and ecto-CRT were all associated with improved relapse-free survival, only CRT exposure significantly correlated with superior overall survival. Thus, CRT exposure represents a novel powerful prognostic biomarker for patients with AML, reflecting the activation of a clinically relevant AML-specific immune response. PMID:27802968

  18. Unveiling the role of PAK2 in CD44 mediated inhibition of proliferation, differentiation and apoptosis in AML cells

    KAUST Repository

    Aldehaiman, Mansour M.


    the success of the differentiation agent, All-trans retinoic acid (ATRA), in the treatment of acute promyelocytic leukemia (APL), much effort has gone into trying to find agents that are able to differentiate AML cells and specifically the leukemic stem cell

  19. Philologie im Horizont der Geschichtlichkeit von Sprache und Text: zum Tagungsband von Wulf Oesterreicher und Maria Selig

    Directory of Open Access Journals (Sweden)

    Olaf Müller


    Full Text Available Wulf Oesterreicher und Maria Selig, Hrsg., Geschichtlichkeit von Sprache und Text: Philologien – Disziplingenese – Wissenschaftshistoriographie (Paderborn: Wilhelm Fink, 2014, 332 S.

  20. Zoophilie in Zoologie und Roman: Sex und Liebe zwischen Mensch und Tier bei Plutarch, Plinius dem Älteren, Aelian und Apuleius

    Directory of Open Access Journals (Sweden)

    Judith Hindermann


    Full Text Available Die Bedeutung von Zoophilie in der antiken Literatur wurde bislang – mit Ausnahme des Mythos – kaum untersucht. Überblickt man die überlieferten literarischen Texte, fällt auf, dass Zoophilie ausserhalb des Mythos vor allem in zwei literarischen Gattungen auftritt : Einerseits in den zoologischen Schriften von Plutarch, Plinius dem Älteren und Aelian, andererseits im antiken Roman, d.h. in den Metamorphosen des Apuleius und im pseudo-lukianischen Onos. In diesem Beitrag soll untersucht werden, welche Funktion Zoophilie in den beiden literarischen Gattungen hat und wie die Autoren die sexuelle Praktik bewerten, die weder nach griechischem noch römischen Recht strafbar war. Da Vorstellungen über Tiere eng mit Gender und Geschlechterhierarchien verbunden sind, soll insbesondere die Frage berücksichtigt werden, inwiefern männliche und weibliche Verhaltens- und Rollenzuschreibungen bei der Darstellung zoophiler Akte wirksam werden.

  1. Development and implementation of the waste diversion program at MDS Nordion's Cobalt Operations Facility

    International Nuclear Information System (INIS)

    Wasiak, T.


    Historically, the MDS Nordion (MDSN) Cobalt Operations Facility sent solid waste for disposal to Atomic Energy of Canada Ltd.'s Chalk River Laboratories (AECL-CRL). A large portion of this waste was not contaminated. Because this non-contaminated waste originated in the 'active area' of the MDSN facility, it was routinely disposed of as low-level active waste. In 2002, MDSN undertook an initiative to develop and implement a more sophisticated and more economical waste management program. The Waste Diversion Program (WDP) ensures continued environmental and public protection, and reduces the demand on Canada's limited capacity for storage of radioactive material and the associated operating costs. The goal of the WDP is to reduce the volume of waste currently being shipped to AECL-CRL's Waste Management Operation as low-level active waste. The presentation discusses key elements of both the development and the implementation of WDP. It focuses on the following areas: the regulatory environment surrounding the waste disposal issues in Canada and abroad. Methods used by MDSN for determination of radionuclides, which could be present in the facility. Choice of equipment and calculation of individual alarm levels for each identified radionuclide. Key elements of the practical implementation of the program. CNSC Regulatory approval process. The bottom line - dollars and cents. The primary objective of the WDP is to ensure that only waste, which meets regulatory requirements, is diverted from the solid active waste stream. This has been successfully accomplished in MDSN's Cobalt Operations Facility. The objective of the presentation is to share the knowledge and experience obtained in the development process, and thus provide a guideline for other nuclear facilities interested in establishing similar proactive and cost effective programs. (author)

  2. Adaptation of Mouse Skeletal Muscle to Long-Term Microgravity in the MDS Mission (United States)

    Camerino, Giulia M.; Bianchini, Elisa; Ciciliot, Stefano; Danieli-Betto, Daniela; Dobrowolny, Gabriella; Furlan, Sandra; Germinario, Elena; Goto, Katsumasa; Gutsmann, Martina; Kawano, Fuminori; Nakai, Naoya; Ohira, Takashi; Ohno, Yoshitaka; Picard, Anne; Salanova, Michele; Schiffl, Gudrun; Blottner, Dieter; Musarò, Antonio; Ohira, Yoshinobu; Betto, Romeo; Conte, Diana; Schiaffino, Stefano


    The effect of microgravity on skeletal muscles has so far been examined in rat and mice only after short-term (5–20 day) spaceflights. The mice drawer system (MDS) program, sponsored by Italian Space Agency, for the first time aimed to investigate the consequences of long-term (91 days) exposure to microgravity in mice within the International Space Station. Muscle atrophy was present indistinctly in all fiber types of the slow-twitch soleus muscle, but was only slightly greater than that observed after 20 days of spaceflight. Myosin heavy chain analysis indicated a concomitant slow-to-fast transition of soleus. In addition, spaceflight induced translocation of sarcolemmal nitric oxide synthase-1 (NOS1) into the cytosol in soleus but not in the fast-twitch extensor digitorum longus (EDL) muscle. Most of the sarcolemmal ion channel subunits were up-regulated, more in soleus than EDL, whereas Ca2+-activated K+ channels were down-regulated, consistent with the phenotype transition. Gene expression of the atrophy-related ubiquitin-ligases was up-regulated in both spaceflown soleus and EDL muscles, whereas autophagy genes were in the control range. Muscle-specific IGF-1 and interleukin-6 were down-regulated in soleus but up-regulated in EDL. Also, various stress-related genes were up-regulated in spaceflown EDL, not in soleus. Altogether, these results suggest that EDL muscle may resist to microgravity-induced atrophy by activating compensatory and protective pathways. Our study shows the extended sensitivity of antigravity soleus muscle after prolonged exposition to microgravity, suggests possible mechanisms accounting for the resistance of EDL, and individuates some molecular targets for the development of countermeasures. PMID:22470446

  3. Adaptation of mouse skeletal muscle to long-term microgravity in the MDS mission.

    Directory of Open Access Journals (Sweden)

    Dorianna Sandonà

    Full Text Available The effect of microgravity on skeletal muscles has so far been examined in rat and mice only after short-term (5-20 day spaceflights. The mice drawer system (MDS program, sponsored by Italian Space Agency, for the first time aimed to investigate the consequences of long-term (91 days exposure to microgravity in mice within the International Space Station. Muscle atrophy was present indistinctly in all fiber types of the slow-twitch soleus muscle, but was only slightly greater than that observed after 20 days of spaceflight. Myosin heavy chain analysis indicated a concomitant slow-to-fast transition of soleus. In addition, spaceflight induced translocation of sarcolemmal nitric oxide synthase-1 (NOS1 into the cytosol in soleus but not in the fast-twitch extensor digitorum longus (EDL muscle. Most of the sarcolemmal ion channel subunits were up-regulated, more in soleus than EDL, whereas Ca(2+-activated K(+ channels were down-regulated, consistent with the phenotype transition. Gene expression of the atrophy-related ubiquitin-ligases was up-regulated in both spaceflown soleus and EDL muscles, whereas autophagy genes were in the control range. Muscle-specific IGF-1 and interleukin-6 were down-regulated in soleus but up-regulated in EDL. Also, various stress-related genes were up-regulated in spaceflown EDL, not in soleus. Altogether, these results suggest that EDL muscle may resist to microgravity-induced atrophy by activating compensatory and protective pathways. Our study shows the extended sensitivity of antigravity soleus muscle after prolonged exposition to microgravity, suggests possible mechanisms accounting for the resistance of EDL, and individuates some molecular targets for the development of countermeasures.

  4. Recht und soziales Kapital im Wohlfahrtsstaat


    Karstedt, Susanne


    'Das Konzept des sozialen Kapitals spielt eine zentrale Rolle in der Diskussion um den Um- und Abbau des Wohlfahrtsstaates. Zerstört der Wohlfahrtsstaat soziales Kapital? Können staatliche Sozialleistungen durch das soziale Kapital in Familien, Nachbarschaften und Gemeinden umstandslos ersetzt werden, und individuelle Rechtsansprüche als Forderungen an diese sozialen Netzwerke zurückverwiesen werden? Kann die angestrebte 'Verantwortungsgesellschaft' (Etzioni) die Leistungen übernehmen, mit de...

  5. Variationen und ihre Kompensation in CMOS Digitalschaltungen


    Baumann, Thomas


    Variationen bei der Herstellung und während des Betriebs von CMOS Schaltungen beeinflussen deren Geschwindigkeit und erschweren die Verifikation der in der Spezifikation zugesicherten Eigenschaften. In dieser Arbeit wird eine abstraktionsebenenübergreifende Vorgehensweise zur Abschätzung des Einflusses von Prozess- und betriebsbedingten Umgebungsvariationen auf die Geschwindigkeit einer Schaltung vorgestellt. Neben Untersuchungen der Laufzeitsensitivität in low-power CMOS Technologien von...

  6. Von Medien, Übertragungen und Automaten

    Directory of Open Access Journals (Sweden)

    Alessandro Barberi


    Full Text Available Im Zuge der Debatten zum Medialen Habitus wurde vielfach betont, dass die >Theorie der Praxispraxeologischen Medientheorie< des Medialen Habitus avant la lettre gesprochen werden kann. Dieser Artikel untersucht – ausgehend von den Debatten zur "Medienkompetenz" – wie Bourdieu Sprache, Sprechen und Diskurs, sowie Akteure, Felder und Habitus als Medien begreift und betont dabei die Nützlichkeit der Bourdieuschen Bildungssoziologie im Rahmen einer sozialwissenschaftlichen Grundlegung der Medienpädagogik.

  7. Verletzungen und Fehlbeanspruchungen im leistungsorientierten Rudersport


    Bussian, Marc Robert


    Die Stellung der Breitensportart Rudern als gesundheitsfördernde Sportform ist in der Literatur gleichlautend positiv beschrieben. Im leistungsorientierten Rudersport müssen neben den Verletzungen und Fehlbeanspruchungen der eigentlichen Sportart die unabdingbaren Nebentrainingsformen berücksichtigt werden. In den neunziger Jahren vollzog sich ein trainingsmethodischer Wandel, die Einführung eines erschwinglichen Rudersimulators und eine technische Weiterentwicklung im Boots- und Ruderbau. Ei...

  8. Pflege und Beruf: ungleiche Chancen der Vereinbarkeit


    Keck, Wolfgang


    Die Vereinbarkeit von Beruf und Pflege wird in der Öffentlichkeit zu wenig thematisiert. Pflegende in einkommensschwachen Familien können sich keine zusätzlichen Pflegedienste leisten und müssen häufiger Einschnitte im Beruf in Kauf nehmen. Beschäftigte in unteren Hierarchieebenen können Beruf und Pflege nur schwer vereinbaren, da sie flexible Arbeitszeitregelungen seltener nutzen können.

  9. Polnische qualitative Soziologie: Entwicklung und Hauptthemen


    Konecki, Krzysztof T.; Kacperczyk, Anna M.; Marciniak, Lukasz T.


    In dem vorliegenden Beitrag wird die Entwicklung der qualitativen Soziologie in Polen rekonstruiert, indem deren wesentliche intellektuelle Wurzeln und einige Hauptthemen der polnischen Soziologie vorgestellt werden. Romantizismus und die induktive Methode sind essenzielle Elemente für die Entwicklung der Disziplin in Polen gewesen und Charakteristika ihrer Besonderheit. Die Bedeutung von Florian ZNANIECKI für die Entstehung der polnischen qualitativen Soziologie wird gewürdigt. URN: urn:n...

  10. Bedeutung von Umwelt- und Organismusfaktoren bei Autoaggressionen


    Rohmann, Ulrich H.; Elbing, Ulrich; Hartmann, Hellmut


    In der vorliegenden Arbeit werden übergeordnete Hypothesen zu autoaggressiven Verhaltensweisen formuliert, wobei prozeßhafte Abläufe von umweltbezogenen und organischen Variablen angenommen werden. Eine solche dynamische Beziehung hat ihre Bedeutung sowohl für verursachende als auch aufrechterhaltende Faktoren. In einer Querschnittuntersuchung lassen sich Korrelationen von Tageszeit- und Tätigkeitscharakteristiken (umweltbezogene Variablen) zur Autoaggressionshäufigkeit und Pulsfrequenz (Orga...

  11. The novel AML stem cell associated antigen CLL-1 aids in discrimination between normal and leukemic stem cells. (United States)

    van Rhenen, Anna; van Dongen, Guus A M S; Kelder, Angèle; Rombouts, Elwin J; Feller, Nicole; Moshaver, Bijan; Stigter-van Walsum, Marijke; Zweegman, Sonja; Ossenkoppele, Gert J; Jan Schuurhuis, Gerrit


    In CD34(+) acute myeloid leukemia (AML), the malignant stem cells reside in the CD38(-) compartment. We have shown before that the frequency of such CD34(+)CD38(-) cells at diagnosis correlates with minimal residual disease (MRD) frequency after chemotherapy and with survival. Specific targeting of CD34(+)CD38(-) cells might thus offer therapeutic options. Previously, we found that C-type lectin-like molecule-1 (CLL-1) has high expression on the whole blast compartment in the majority of AML cases. We now show that CLL-1 expression is also present on the CD34(+)CD38(-) stem- cell compartment in AML (77/89 patients). The CD34(+)CLL-1(+) population, containing the CD34(+)CD38(-)CLL-1(+) cells, does engraft in nonobese diabetic/severe combined immunodeficiency (NOD/SCID) mice with outgrowth to CLL-1(+) blasts. CLL-1 expression was not different between diagnosis and relapse (n = 9). In remission, both CLL-1(-) normal and CLL-1(+) malignant CD34(+)CD38(-) cells were present. A high CLL-1(+) fraction was associated with quick relapse. CLL-1 expression is completely absent both on CD34(+)CD38(-) cells in normal (n = 11) and in regenerating bone marrow controls (n = 6). This AML stem-cell specificity of the anti-CLL-1 antibody under all conditions of disease and the leukemia-initiating properties of CD34(+)CLL-1(+) cells indicate that anti-CLL-1 antibody enables both AML-specific stem-cell detection and possibly antigen-targeting in future.

  12. The Runt domain of AML1 (RUNX1) binds a sequence-conserved RNA motif that mimics a DNA element. (United States)

    Fukunaga, Junichi; Nomura, Yusuke; Tanaka, Yoichiro; Amano, Ryo; Tanaka, Taku; Nakamura, Yoshikazu; Kawai, Gota; Sakamoto, Taiichi; Kozu, Tomoko


    AML1 (RUNX1) is a key transcription factor for hematopoiesis that binds to the Runt-binding double-stranded DNA element (RDE) of target genes through its N-terminal Runt domain. Aberrations in the AML1 gene are frequently found in human leukemia. To better understand AML1 and its potential utility for diagnosis and therapy, we obtained RNA aptamers that bind specifically to the AML1 Runt domain. Enzymatic probing and NMR analyses revealed that Apt1-S, which is a truncated variant of one of the aptamers, has a CACG tetraloop and two stem regions separated by an internal loop. All the isolated aptamers were found to contain the conserved sequence motif 5'-NNCCAC-3' and 5'-GCGMGN'N'-3' (M:A or C; N and N' form Watson-Crick base pairs). The motif contains one AC mismatch and one base bulged out. Mutational analysis of Apt1-S showed that three guanines of the motif are important for Runt binding as are the three guanines of RDE, which are directly recognized by three arginine residues of the Runt domain. Mutational analyses of the Runt domain revealed that the amino acid residues used for Apt1-S binding were similar to those used for RDE binding. Furthermore, the aptamer competed with RDE for binding to the Runt domain in vitro. These results demonstrated that the Runt domain of the AML1 protein binds to the motif of the aptamer that mimics DNA. Our findings should provide new insights into RNA function and utility in both basic and applied sciences.

  13. Rechtspopulistische Einstellungen in Ost- und Westdeutschland

    Directory of Open Access Journals (Sweden)

    Beate Küpper


    Full Text Available Während sich die Mehrheit der Deutschen für Demokratie, Vielfalt und Gleichwertigkeit positioniert, sind zugleich rechtspopulistische Einstellungen lauter geworden. Der Beitrag berichtet über Befunde der Mitte-Studie der Friedrich-Ebert-Stiftung 2016 zu der Verbreitung rechtspopulistischer und rechtsextreme Einstellungen, wirft einen besonderen Blick auf potentielle Wähler_innen der AfD und diskutiert am Ende mögliche Erklärungen für die gefundenen Unterschiede zwischen Ost- und Westdeutschen.

  14. Editorial 01/2013 Normen und Normierungen

    Directory of Open Access Journals (Sweden)

    Christian Swertz


    Full Text Available Auf unterschiedlichsten Ebenen werden die Diskussionen und Forschungen der Medienpädagogik von normativ aufgeladenen Begriffen durchzogen: so, wenn es um Standards in der Medienbildung geht, wenn beispielsweise diskutiert wird, welche Inhalte in welcher Form vermittelt werden sollen; so auch wenn zur Debatte steht, wie Medienpädagogik institutionalisiert werden sollte und welche Voraussetzungen gegeben sein müssen, um einen geplanten Bildungsprozess zu lenken oder anzuleiten.Derartige Norm(ierungen wurden bereits mit der Konzeptualisierung des Begriffs Medienkompetenz und im Blick auf die Emanzipation des Menschen kritisch beleuchtet, womit auch Kritik an gesellschaftlichen Herrschafts- und Machtstrukturen verbunden war. Die Orientierung an der sozialwissenschaftlich verstandenen Emanzipation des Menschen ist allerdings in anderen pädagogischen Disziplinen durchaus umstritten. Gleichzeitig ist zu beobachten, dass die gesellschaftskritische Perspektive im medienpädagogischen Diskurs über die Orientierung von Medienkompetenz und Medienbildung eine immer geringere Rolle spielt. Deshalb hat sich die Redaktion der MEDIENIMPULSE entschlossen, dem Thema Normen und Normierungen eine eigene Ausgabe zu widmen.Dabei sollten folgende Fragen behandelt werden:Wie sieht es mit Norm(ierungen im Bereich der Mediendidaktik aus? Wie sind die mit aktuellen Medienkompetenz- und Medienbildungsbegriffen verbundenen Normen epistemologisch und (medientheoretisch abgestützt? Wie lassen sich – nur scheinbar paradox formuliert – wissenschaftlich begründbare medienpädagogische Normen finden, die sich den genannten Normierungen widersetzen und entziehen? Inwiefern führt die Einführung von Laptopklassen oder Smartboards im schulischen Bereich oder die Gestaltung von Videospielprojekten in der außerschulischen Medienbildung zu einer unreflektierten Sozialdisziplinierung, die als illegitime Form(atierung des Menschen verstanden werden kann? Der Schwerpunktteil

  15. Medienpädagogik und die Digitale Gesellschaft im Spannungsfeld von Regulierung und Teilhabe

    Directory of Open Access Journals (Sweden)

    Stefan Iske


    Full Text Available Vor 25 Jahren stellte Tim Berners-Lee sein Konzept eines World Wide Web (WWW vor und legte damit einen der bedeutendsten Grundsteine der digitalen Vernetzung. Was ursprünglich zum Austausch von Informationen und Daten unter Forschenden entworfen wurde, hat sich zu einem umfassenden Kultur- und Bildungsraum entwickelt und ist ein universaler und zentraler Dienst des Internet geworden. Dieser gegenwärtige Status des Internet und des World Wide Web ist der vorläufige Zwischenstand einer historischen Entwicklung, der sowohl Transformationen und Veränderungen als auch Konstanten zugrunde liegen. Nicht erst zum diesjährigen Geburtstag des World Wide Web wird deutlich, dass durch digitale und vernetzte Technologien zentrale Kategorien wie Bildung, Erziehung und Sozialisation berührt werden. Beispielhaft kann auf die aktuellen Debatten über Regulierungsmechanismen im Internet wie auch auf die Enthüllungen Edward Snowdens hingewiesen werden. Aus dem Vorangehenden lassen sich medienpädagogische Fragestellungen ableiten, die zum Beispiel die Handlungsautonomie von Subjekten sowie Möglichkeitsräume der Mitgestaltung von und Teilhabe an Gesellschaft (Winter 2012, Swertz 2014 thematisieren. Zudem sind es Fragen der Mediensozialisation und der Konstruktion von Identität in digital vernetzten Räumen (Jörissen/Marotzki 2008, die sowohl bei der Theoriebildung als auch im Rahmen medienpädagogischer Praxis eine hohe Relevanz besitzen.

  16. Steueroasen und Regulierungsoasen – Auswirkungen auf die Stabilität des Finanzmarkts und politische Implikationen

    Directory of Open Access Journals (Sweden)

    Michaela Schmidt


    Full Text Available In diesem Beitrag wird dargelegt, dass Steuer- und Regulierungsoasen nicht nur Steuerausfälle und Kapitalflucht ermöglichen, sondern auch eine Hauptursache für die Finanzkrise 2007/2008 waren und weiterhin die Stabilität des Finanzmarkts gefährden. Sie haben den Boden bereitet für das Aufkommen nicht regulierter Finanzinstitutionen, sogenannter Schattenbanken. Regulierungsoasen ermöglichen Finanzmarktakteuren eine Umgehung von Regulierungs- und Aufsichtsvorschriften und heizen den Wettbewerb um niedrige Regulierungsvorschriften maßgeblich an. Jeder Schritt zu einer finanzpolitischen Re-Regulierung von Steuer- und Regulierungsoasen sowie Schattenbanken ist ein aktiver Schritt zur Krisenvorbeugung und damit zum Schutz der ArbeitnehmerInnen vor den gewaltigen volkswirtschaftlichen Kosten von Finanzkrisen.

  17. Ibrutinib synergizes with poly(ADP-ribose) glycohydrolase inhibitors to induce cell death in AML cells via a BTK-independent mechanism. (United States)

    Rotin, Lianne E; Gronda, Marcela; MacLean, Neil; Hurren, Rose; Wang, XiaoMing; Lin, Feng-Hsu; Wrana, Jeff; Datti, Alessandro; Barber, Dwayne L; Minden, Mark D; Slassi, Malik; Schimmer, Aaron D


    Targeting Bruton's tyrosine kinase (BTK) with the small molecule BTK inhibitor ibrutinib has significantly improved patient outcomes in several B-cell malignancies, with minimal toxicity. Given the reported expression and constitutive activation of BTK in acute myeloid leukemia (AML) cells, there has been recent interest in investigating the anti-AML activity of ibrutinib. We noted that ibrutinib had limited single-agent toxicity in a panel of AML cell lines and primary AML samples, and therefore sought to identify ibrutinib-sensitizing drugs. Using a high-throughput combination chemical screen, we identified that the poly(ADP-ribose) glycohydrolase (PARG) inhibitor ethacridine lactate synergized with ibrutinib in TEX and OCI-AML2 leukemia cell lines. The combination of ibrutinib and ethacridine induced a synergistic increase in reactive oxygen species that was functionally important to explain the observed cell death. Interestingly, synergistic cytotoxicity of ibrutinib and ethacridine was independent of the inhibitory effect of ibrutinib against BTK, as knockdown of BTK did not sensitize TEX and OCI-AML2 cells to ethacridine treatment. Thus, our findings indicate that ibrutinib may have a BTK-independent role in AML and that PARG inhibitors may have utility as part of a combination therapy for this disease.

  18. The rarity of ALDH(+) cells is the key to separation of normal versus leukemia stem cells by ALDH activity in AML patients. (United States)

    Hoang, Van T; Buss, Eike C; Wang, Wenwen; Hoffmann, Isabel; Raffel, Simon; Zepeda-Moreno, Abraham; Baran, Natalia; Wuchter, Patrick; Eckstein, Volker; Trumpp, Andreas; Jauch, Anna; Ho, Anthony D; Lutz, Christoph


    To understand the precise disease driving mechanisms in acute myeloid leukemia (AML), comparison of patient matched hematopoietic stem cells (HSC) and leukemia stem cells (LSC) is essential. In this analysis, we have examined the value of aldehyde dehydrogenase (ALDH) activity in combination with CD34 expression for the separation of HSC from LSC in 104 patients with de novo AML. The majority of AML patients (80 out of 104) had low percentages of cells with high ALDH activity (ALDH(+) cells; cells (≥1.9%; ALDH-numerous AML). In patients with ALDH-rare AML, normal HSC could be separated by their CD34(+) ALDH(+) phenotype, whereas LSC were exclusively detected among CD34(+) ALDH(-) cells. For patients with ALDH-numerous AML, the CD34(+) ALDH(+) subset consisted mainly of LSC and separation from HSC was not feasible. Functional analyses further showed that ALDH(+) cells from ALDH-numerous AML were quiescent, refractory to ARA-C treatment and capable of leukemic engraftment in a xenogenic mouse transplantation model. Clinically, resistance to chemotherapy and poor long-term outcome were also characteristic for patients with ALDH-numerous AML providing an additional risk-stratification tool. The difference in spectrum and relevance of ALDH activity in the putative LSC populations demonstrates, in addition to phenotypic and genetic, also functional heterogeneity of leukemic cells and suggests divergent roles for ALDH activity in normal HSC versus LSC. By acknowledging these differences our study provides a new and useful tool for prospective identification of AML cases in which separation of HSC from LSC is possible. © 2014 UICC.

  19. Erfahrungen an der Schnittstelle von Medienarbeit und Praxisforschung

    Directory of Open Access Journals (Sweden)

    Peter Holzwarth


    Full Text Available Der Beitrag reflektiert die Verbindung von praktischer Medienarbeit und Forschung am Beispiel eines internationalen EU-Forschungsprojekts zum Thema Medien und Migration. Neben didaktischen Prinzipien und Konzepten für die aktive Medienarbeit im Forschungskontext geht es um die Kooperation von medienpädagogischer Begleitung (MB und wissenschaftlicher Begleitung (WB sowie um deren spezifische Kompetenzen.

  20. Leitung und Kooperation in wissenschaftlichen Bibliotheken Berlins - eine empirische Untersuchung


    Paul, Gerhard


    Die vorliegende Arbeit greift ein im bibliotheks- und IuK-wissenschaftlichen sowie im fachprofessionellen Diskurs bisher weitgehend vernachlässigtes, aber immer bedeutsameres Thema auf: das vertikale soziale Geschehen in der Arbeitsorganisation ?wissenschaftliche Bibliothek". Die Absicht der Untersuchung lag darin, einen Zusammenhang zwischen dem Interaktionsverhalten der Leitungspersonen einerseits und der Mobilisierung von Leistungs- und Innovationspotentialen bei den Mitarbeiterinnen und M...

  1. [Sascha Möbius. Das Gedähtnis der Reichsstadt. Unruhen und Kriege in der lübeckischen Chronistik und Kriege und Erinnerungskultur des späten mittelalters und der frühen Neuzeit

    Index Scriptorium Estoniae

    Hormuth, Dennis


    Arvustus: Sascha Möbius. Das Gedähtnis der Reichsstadt. Unruhen und Kriege in der lübeckischen Chronistik und Kriege und Erinnerungskultur des späten mittelalters und der frühen Neuzeit. (Göttingen, 2011)

  2. The development of the Older Persons and Informal Caregivers Survey Minimum DataSet (TOPICS-MDS): a large-scale data sharing initiative. (United States)

    Lutomski, Jennifer E; Baars, Maria A E; Schalk, Bianca W M; Boter, Han; Buurman, Bianca M; den Elzen, Wendy P J; Jansen, Aaltje P D; Kempen, Gertrudis I J M; Steunenberg, Bas; Steyerberg, Ewout W; Olde Rikkert, Marcel G M; Melis, René J F


    In 2008, the Ministry of Health, Welfare and Sport commissioned the National Care for the Elderly Programme. While numerous research projects in older persons' health care were to be conducted under this national agenda, the Programme further advocated the development of The Older Persons and Informal Caregivers Survey Minimum DataSet (TOPICS-MDS) which would be integrated into all funded research protocols. In this context, we describe TOPICS data sharing initiative ( A working group drafted TOPICS-MDS prototype, which was subsequently approved by a multidisciplinary panel. Using instruments validated for older populations, information was collected on demographics, morbidity, quality of life, functional limitations, mental health, social functioning and health service utilisation. For informal caregivers, information was collected on demographics, hours of informal care and quality of life (including subjective care-related burden). Between 2010 and 2013, a total of 41 research projects contributed data to TOPICS-MDS, resulting in preliminary data available for 32,310 older persons and 3,940 informal caregivers. The majority of studies sampled were from primary care settings and inclusion criteria differed across studies. TOPICS-MDS is a public data repository which contains essential data to better understand health challenges experienced by older persons and informal caregivers. Such findings are relevant for countries where increasing health-related expenditure has necessitated the evaluation of contemporary health care delivery. Although open sharing of data can be difficult to achieve in practice, proactively addressing issues of data protection, conflicting data analysis requests and funding limitations during TOPICS-MDS developmental phase has fostered a data sharing culture. To date, TOPICS-MDS has been successfully incorporated into 41 research projects, thus supporting the feasibility of constructing a large (>30,000 observations

  3. Clinical and biological significance of isolated Y chromosome loss in myelodysplastic syndromes and chronic myelomonocytic leukemia. A report from the Spanish MDS Group. (United States)

    Nomdedeu, Meritxell; Pereira, Arturo; Calvo, Xavier; Colomer, Joan; Sole, Francesc; Arias, Amparo; Gomez, Candida; Luño, Elisa; Cervera, Jose; Arnan, Montserrat; Pomares, Helena; Ramos, Fernando; Oiartzabal, Itziar; Espinet, Blanca; Pedro, Carme; Arrizabalaga, Beatriz; Blanco, María Laura; Tormo, Mar; Hernandez-Rivas, Jesus Maria; Díez-Campelo, María; Ortega, Margarita; Valcárcel, David; Cedena, Maria-Teresa; Collado, Rosa; Grau, Javier; Granada, Isabel; Sanz, Guillermo; Campo, Elias; Esteve, Jordi; Costa, Dolors


    Isolate loss of chromosome Y (-Y) in myelodysplastic syndromes (MDS) is associated to a better outcome but it is also well described as an age-related phenomenon. In this study we aimed to analyze the prognostic impact of -Y in the context of the IPSS-R cytogenetic classification, evaluate the clinical significance of the percentage of metaphases with isolated -Y, and test whether finding -Y may predispose to over-diagnose MDS in patients with borderline morphological features. We evaluated 3581 male patients from the Spanish MDS Registry with a diagnosis of MDS or chronic myelomonocytic leukemia (CMML). -Y was identified in 177 patients (4.9%). Compared with the 2246 male patients with normal karyotype, -Y group showed a reduced risk of leukemic transformation that did not translate into a survival advantage. The overall survival and the risk of leukemic transformation were not influenced by the percentage of metaphases with -Y. The -Y group was not enriched in patients with minor morphologic traits of dysplasia, suggesting that the better outcome in the -Y group cannot be explained by enrichment in cases misdiagnosed as MDS. In conclusion, our results support the current recommendation of classifying patients with -Y within the very good risk category of the IPSS-R for MDS and rule out a selection bias as a possible explanation of this better outcome. An analysis of the molecular basis of MDS with isolated -Y would be of interest as it may provide a biological basis of protection against progression to acute leukemia. Copyright © 2017 Elsevier Ltd. All rights reserved.

  4. Thyroid function appears to be significantly reduced in Space-borne MDS mice (United States)

    Saverio Ambesi-Impiombato, Francesco; Curcio, Francesco; Fontanini, Elisabetta; Perrella, Giuseppina; Spelat, Renza; Zambito, Anna Maria; Damaskopoulou, Eleni; Peverini, Manola; Albi, Elisabetta

    It is known that prolonged space flights induced changes in human cardiovascular, muscu-loskeletal and nervous systems whose function is regulated by the thyroid gland but, until now, no data were reported about thyroid damage during space missions. We have demonstrated in vitro that, during space missions (Italian Soyuz Mission "ENEIDE" in 2005, Shuttle STS-120 "ESPERIA" in 2007), thyroid in vitro cultured cells did not respond to thyroid stimulating hor-mone (TSH) treatment; they appeared healthy and alive, despite their being in a pro-apopotic state characterised by a variation of sphingomyelin metabolism and consequent increase in ce-ramide content. The insensitivity to TSH was largely due to a rearrangement of specific cell membrane microdomains, acting as platforms for TSH-receptor (TEXUS-44 mission in 2008). To study if these effects were present also in vivo, as part of the Mouse Drawer System (MDS) Tissue Sharing Program, we performed experiments in mice maintained onboard the Interna-tional Space Station during the long-duration (90 days) exploration mission STS-129. After return to earth, the thyroids isolated from the 3 animals were in part immediately frozen to study the morphological modification in space and in part immediately used to study the effect of TSH treatment. For this purpose small fragments of tissue were treated with 10-7 or 10-8 M TSH for 1 hour by using untreated fragments as controls. Then the fragments were fixed with absolute ethanol for 10 min at room temperature and centrifuged for 20 min. at 3000 x g. The supernatants were used for cAMP analysis whereas the pellet were used for protein amount determination and for immunoblotting analysis of TSH-receptor, sphingomyelinase and sphingomyelin-synthase. The results showed a modification of the thyroid structure and also the values of cAMP production after treatment with 10-7 M TSH for 1 hour were significantly lower than those obtained in Earth's gravity. The treatment with TSH

  5. Genetics of therapy-related myelodysplasia and acute myeloid leukemia

    DEFF Research Database (Denmark)

    Pedersen-Bjergaard, J.; Andersen, Mette Klarskov; Andersen, M.T.


    Myelodysplasia (MDS) and acute myeloid leukemia (AML) are heterogeneous, closely associated diseases arising de novo or following chemotherapy with alkylating agents, topoisomerase II inhibitors, or after radiotherapy. Whereas de novo MDS and AML are almost always subclassified according...

  6. Nachhaltiger Lebensmittelkonsum gestern, heute und morgen

    DEFF Research Database (Denmark)

    Aschemann-Witzel, Jessica


    Die Weltgemeinschaft sieht sich mit steigendem Bevölkerungswachstum und Zielkonflikten der Nutzung von Land und Agrarrohstoffen konfrontiert. Dies wirft die Frage auf, wie nachhaltiger Lebensmittelkonsum in der Zukunft auszusehen hat. Der Beitrag diskutiert die Frage aus Sicht der Konsumverhaltens...

  7. Ruhende Flüssigkeiten und Gase (United States)

    Heintze, Joachim

    Das mechanische Verhalten von Flüssigkeiten und Gasen ist dadurch gekennzeichnet, dass sie keine statische Schubfestigkeit besitzen, andernfalls würden sie nicht beginnen, zu fließen. In ruhenden Flüssigkeiten und Gasen können daher keine Schubspannungen bestehen:

  8. Handlung und Kommunikation als Grundbegriffe der Soziologie

    NARCIS (Netherlands)

    Martens, W.P.M.; Albert, H.; Greshoff, R.; Schützeichel, R.


    Handlung und Kommunikation gelten in der Soziologie manchmal als alternative, konkurrierende Grundbegriffe für die Beschreibung und Erklärung sozialer Zusammenhänge (siehe u.a. Luhmann 1984; 1990; Schneider 1994; Stichweh 2000; Greshoff 1999; Schwinn 2001; Albert et. al. 2003). Eine Soziologie,

  9. Die Gestalten und das Gestalten der Welt

    NARCIS (Netherlands)

    Ierna, Carlo; Höfer, Ulf; Valent, Juta


    In seiner Kosmogonie bespricht Ehrenfels den Ursprung, die Entwicklung, und das endgültige Schicksal des Universums: die Gestalt der Welt. Einerseits ist sie ein Kosmos, ein Geschöpf des Ordnungsprinzips, andererseits ein Chaos, als Resultat des Prinzips des Zufalls und der Entropie. Diese beiden

  10. Systeme im Einsatz. Lernmanagement, Kompetenzmanagement und PLE

    NARCIS (Netherlands)

    Kalz, Marco; Schön, Sandra; Lindner, Martin; Roth, Detlev; Baumgartner, Peter


    Kalz, M., Schön, S., Lindner, M., Roth, D., & Baumgartner, P. (2011). Systeme im Einsatz. Lernmanagement, Kompetenzmanagement und PLE. In M. Ebner, & S. Schön (Eds.), L3T - Lerhbuch für Lernen und Lehren mit Technologie (pp. 111-118). Graz, Austria: Uni Graz. Available at

  11. Schaulust und Horror Soziokulturelle - Perspektiven auf PEEPING TOM

    Directory of Open Access Journals (Sweden)

    Thomas Ballhausen


    Full Text Available Die Geschichte des Kinos und des Films ist mindestens ebenso sehr eine Geschichte des Schreckens (und der damit verbundenen Schaulust wie sie eine Geschichte des Dokumentarischen zu sein scheint. Es sind die außergewöhnlichen Körper und deren Bewegungen, die das Publikum zu allen Zeiten faszinierten, schockierten und zum Schauen und Sehen lockten. Besonders das Genre des Horrorfilms ist mit diesem zentralen Aspekt des Kinos besonders deutlich verbunden.

  12. Quantitative Analyse und Visualisierung der Herzfunktionen (United States)

    Sauer, Anne; Schwarz, Tobias; Engel, Nicole; Seitel, Mathias; Kenngott, Hannes; Mohrhardt, Carsten; Loßnitzer, Dirk; Giannitsis, Evangelos; Katus, Hugo A.; Meinzer, Hans-Peter

    Die computergestützte bildbasierte Analyse der Herzfunktionen ist mittlerweile Standard in der Kardiologie. Die verfügbaren Produkte erfordern meist ein hohes Maß an Benutzerinteraktion und somit einen erhöhten Zeitaufwand. In dieser Arbeit wird ein Ansatz vorgestellt, der dem Kardiologen eine größtenteils automatische Analyse der Herzfunktionen mittels MRT-Bilddaten ermöglicht und damit Zeitersparnis schafft. Hierbei werden alle relevanten herzphysiologsichen Parameter berechnet und mithilfe von Diagrammen und Graphen visualisiert. Diese Berechnungen werden evaluiert, indem die ermittelten Werte mit manuell vermessenen verglichen werden. Der hierbei berechnete mittlere Fehler liegt mit 2,85 mm für die Wanddicke und 1,61 mm für die Wanddickenzunahme immer noch im Bereich einer Pixelgrösse der verwendeten Bilder.

  13. Sowjetunion und Völkerrecht 1962-1973 / Henn-Jüri Uibopuu

    Index Scriptorium Estoniae

    Uibopuu, Henn-Jüri, 1929-2012


    Tutvustus: Sowjetunion und Völkerrecht 1962-1973 : Bibliographie und analyse / hrsg. Boris Meissner, Dietrich Frenzke und Erika Chilicki. Köln : Wissenschaft und Politik, 1979 [t.p. incorrectly: 1977

  14. Granulocytic Sarcoma by AML M4eo (inv16 after Allogeneic Stem Cell Transplantation without Bone Marrow Involvement

    Directory of Open Access Journals (Sweden)

    Stephan Zaenker


    Full Text Available Granulocytic sarcoma (GS represents a rare type of extramedullar manifestation from the acute myeloid leukaemia (AML. We report the case of a patient with recurrences of AML M4eo leukaemia in the uterus and the small intestine at 3 and 5 years, respectively, after matched related peripheral blood stem cell transplantation (PBSCT. The patient underwent the withdrawal of immunosuppression, hysterectomy, and local irradiation at first relapse, as well as systemic chemotherapy and donor lymphocyte infusions at second recurrence, inducing a second and third complete remission, respectively. At year six after transplantation, the patient experienced disease progression by meningeosis leukaemia to which she succumbed despite intrathecal chemotherapy. Following allogeneic stem cell transplantation, awareness for atypical manifestations of granulocytic sarcoma appears prudent, the cellular immunotherapy should aim at immunological disease control.

  15. Incidence of extramedullary relapse after haploidentical SCT for advanced AML/myelodysplastic syndrome. (United States)

    Yoshihara, S; Ikegame, K; Kaida, K; Taniguchi, K; Kato, R; Inoue, T; Fujioka, T; Tamaki, H; Okada, M; Soma, T; Ogawa, H


    Extramedullary (EM) relapse of leukemia after allo-SCT in patients with AML/myelodysplastic syndrome has been increasingly reported. The reduced effectiveness of the GVL effect in EM sites, as compared with BM, has been suggested to underlie this problem. We retrospectively analyzed the pattern of relapse after haploidentical SCT (haplo-SCT), performed as the first or second SCT. Among 38 patients who received haplo-SCT as their first SCT, the cumulative incidences of BM and EM relapse at 3 years were 40.5 and 10.9%, respectively. Among 19 patients who received haplo-SCT as their second SCT, the cumulative incidences of BM and EM relapse were 30.9 and 31.9%, respectively. Moreover, most of the patients who underwent repeat haplo-SCT for the treatment of EM relapse had further EM relapse at other sites. Post-relapse survival did not differ significantly with different patterns of relapse. The frequent occurrence of EM relapse after haplo-SCT, particularly when performed as a second SCT, suggests that the potent GVL effect elicited by an HLA disparity also occurs preferentially in BM. Our findings emphasize the need for a treatment strategy for EM relapse that recognizes the reduced susceptibility of EM relapse to the GVL effect.

  16. Chemical Space of FLT3 Inhibitors as Potential Anti-AML Drugs. (United States)

    Lan, Qing-Yuan; Zhi, Yan-Le; Heng, Hao; Tian, Jie-Yi; Guo, Xiao-Xing; Liu, Hai-Chun; Chen, Ya-Dong; Lu, Tao; Lu, Shuai


    FLT3 is a member of receptor tyrosine kinase III family, mainly expressed in hematopoietic cells. The aberrant expression and function of FLT3 are strongly related to leukemia, especially acute myeloid leukemia. Its varieties of amino-acid residues mutations, such as FLT3-ITDs and -TKDs, can induce constant proliferation of hematological tumor cells with poor prognosis. Hence FLT3 serves as a promising target in AML chemotherapy. This review focused on the progress of FLT3 inhibitors study including those that have entered clinical trials or were reported in numerous patents all over the world. Thus, we provided a useful reference for the development of new anti-leukemia drugs. Through a comprehensive retrospective study, FLT3 inhibitors in several patent applications were identified and classified into five categories, including quinolone-related, indole-related, ureas, pyrimidines and other compounds. For each category of compounds, the structural feature, SAR, biological activity and current research status were thoroughly reviewed and analyzed. Although some of those compounds expressed potent bioactivities and have reached the advanced clinical trials for the treatment of leukemia, there are still several problems need to be faced before they enter the market eventually, especially the drug resistance issue. The improvement of therapeutic potency for FLT3 inhibitors might depend on the useful combination therapy and further refinement of the intrinsic properties of FLT3 inhibitors. Copyright© Bentham Science Publishers; For any queries, please email at

  17. Benefit of high-dose daunorubicin in AML induction extends across cytogenetic and molecular groups. (United States)

    Luskin, Marlise R; Lee, Ju-Whei; Fernandez, Hugo F; Abdel-Wahab, Omar; Bennett, John M; Ketterling, Rhett P; Lazarus, Hillard M; Levine, Ross L; Litzow, Mark R; Paietta, Elisabeth M; Patel, Jay P; Racevskis, Janis; Rowe, Jacob M; Tallman, Martin S; Sun, Zhuoxin; Luger, Selina M


    The initial report of the Eastern Cooperative Oncology Group-American College of Radiology Imaging Network Cancer Research Group trial E1900 (#NCT00049517) showed that induction therapy with high-dose (HD) daunorubicin (90 mg/m(2)) improved overall survival in adults cytogenetics or aFLT3-ITD mutation. Here, we update the results of E1900 after longer follow-up (median, 80.1 months among survivors), focusing on the benefit of HD daunorubicin on common genetic subgroups. Compared with standard-dose daunorubicin (45 mg/m(2)), HD daunorubicin is associated with a hazard ratio (HR) for death of 0.74 (P= .001). Younger patients (cytogenetics (HR, 0.51;P= .03 and HR, 0.68;P= .01, respectively). Patients with unfavorable cytogenetics were shown to benefit from HD daunorubicin on multivariable analysis (adjusted HR, 0.66;P= .04). Patients with FLT3-ITD (24%),DNMT3A(24%), and NPM1(26%) mutant AML all benefited from HD daunorubicin (HR, 0.61,P= .009; HR, 0.62,P= .02; and HR, 0.50,P= .002; respectively). HD benefit was seen in the subgroup of older patients (50-60 years) with the FLT3-ITD or NPM1 mutation. Additionally, the presence of an NPM1 mutation confers a favorable prognosis only for patients receiving anthracycline dose intensification during induction. © 2016 by The American Society of Hematology.

  18. Bewegung bei Vorschulkindern: Empfehlungen und Wirklichkeit

    Directory of Open Access Journals (Sweden)

    Graf C


    Full Text Available Bewegung und körperliche Aktivität spielen insbesondere in der ganzheitlichen Entwicklung von Kindern eine wichtige Rolle. Heutzutage ist der kindliche Lebensstil allerdings von Bewegungsarmut und der Nutzung audiovisueller Medien geprägt. Bereits Kindergartenkinder sind überwiegend inaktiv bzw. verbringen viel Zeit mit Fernsehen. Eine mögliche Folge von mangelnder Bewegung können motorische Defizite darstellen. In eigenen Kollektiven schneiden mindestens 45 % der Kinder unterdurchschnittlich in den motorischen Hauptbeanspruchungsformen Koordination, Kraft und Schnelligkeit ab. Inwiefern sich dies langfristig auf die gesunde körperliche, aber auch geistige und emotionale Entwicklung der Kinder auswirkt, kann derzeit noch nicht beantwortet werden. Sicherlich unterstützen aber motorische Defizite ein Meidungsverhalten und den weiteren Rückzug aus der Bewegung sowie die Entwicklung von Übergewicht und Adipositas. Allgemein wird für Kinder in dieser Altersgruppe mindestens 2 Stunden tägliche Bewegungszeit sowie eine Reduktion der Fernsehzeit auf maximal 30 Min. empfohlen. Um diese Ziele zu erreichen bzw. zu unterstützen, sind effektive präventive Programme in den verschiedenen Lebensräumen der Kinder, Kindergärten, aber auch pädiatrischen Praxen etc. vonnöten. Bislang ist kein gesundheitsförderlicher/ präventiver „Königsweg“ bekannt, insbesondere nicht für Risikofamilien mit einem geringen sozioökonomischen Status und/oder Migrationshintergrund. Wichtig erscheinen aber die Förderung der intersektoralen Zusammenarbeit und ein Schwerpunkt in der Planung und Umsetzung auf Qualitätssicherung und Projektmanagement, um auch nachhaltig die Gesundheit der Kinder zu unterstützen.

  19. Therapy-Related Myelodysplastic Syndrome Following Treatment for Childhood Acute Lymphoblastic Leukemia: Outcome of Patients Registered in the EWOG-MDS 98/06 Studies

    DEFF Research Database (Denmark)

    Strahm, Birgitte; Amann, Roland; De Moerloose, Barbara

    Objective: Therapy-related myelodysplastic syndrome (tMDS) following treatment of childhood acute lymphoblastic leukemia (ALL) is one of the most frequently observed secondary malignancies in survivors of childhood cancer. Allogeneic stem cell transplantation (SCT) is the only curative treatment....... This analysis was performed to asses the outcome of patients with tMDS following treatment for childhood ALL reported to the EWOG-MDS study group. Patients and Transplant Procedure: Forty-three patients (19 male/24 female) were diagnosed with tMDS between August 1989 and August 2009. The median age at diagnosis...... was 8.9 yrs (3.4–20.5). The median interval from diagnosis of ALL to the diagnosis of tMDS was 3.3 yrs (1.7–7.0). Five patients did not receive SCT and died due to progressive disease at a median of 5.6 mo after diagnosis. Thirty-eight patients were transplanted. One patient was excluded from...

  20. Compliance with the AM+L4776L/CFT International Standard; Lessons from a Cross-Country Analysis


    Concha Verdugo Yepes


    This paper assesses countries' compliance with the Anti-Money Laundering and Combating the Financing of Terrorism (AML/CFT) international standard during the period 2004 to 2011. We find that overall compliance is low; there is an adverse impact on financial transparency created by the cumulative effects of poor implementation of standards on customer identification; and the current measurements of compliance do not take into account an analysis of ML/FT risk, thereby undermining their credib...

  1. Comparing cancer vs normal gene expression profiles identifies new disease entities and common transcriptional programs in AML patients

    DEFF Research Database (Denmark)

    Rapin, Nicolas; Bagger, Frederik Otzen; Jendholm, Johan


    Gene expression profiling has been used extensively to characterize cancer, identify novel subtypes, and improve patient stratification. However, it has largely failed to identify transcriptional programs that differ between cancer and corresponding normal cells and has not been efficient in iden......-karyotype AML, which allowed for the generation of a highly prognostic survival signature. Collectively, our CvN method holds great potential as a tool for the analysis of gene expression profiles of cancer patients....

  2. Keep your mind off negative things: coping with long-term effects of acute myeloid leukemia (AML). (United States)

    Ghodraty-Jabloo, Vida; Alibhai, Shabbir M H; Breunis, Henriette; Puts, Martine T E


    Acute myeloid leukemia (AML) is characterized by sudden onset, intensive treatment, a poor prognosis, and significant relapse risk. Quality of life (QOL) and well-being among AML survivors have been extensively studied during the 6 months of active treatment. However, it is not clear what survivors experience after active treatment. The purpose of our study was to explore how AML survivors describe their longer-term physical and psychosocial well-being and how they cope with these challenges. We conducted a prospective qualitative study and interviewed 19 adult participants (11 had completed treatment, 8 were receiving maintenance chemotherapy). Data were collected using semi-structured interviews that were audio-recorded and transcribed verbatim. The grounded theory approach was used for data analysis. A marked improvement in physical health was reported; however, psychosocial well-being was compromised by enduring emotional distress. A range of emotion- and problem-focused coping strategies were reported. Keeping one's mind off negative things through engaging in formal work or informal activities and seeking control were the two most commonly used coping strategies. Seeking social support for reassurance was also common. Problem-focused strategies were frequently described by the ongoing treatment group to manage treatment side effects. Although physical symptoms improved after completion of treatment, psychosocial distress persisted over longer period of time. In addition, essential needs of AML survivors shifted across survivorship as psychological burden gradually displaced physical concerns. The integral role of coping mechanisms in the adaptation process suggests a need for effective and ongoing psychological interventions.

  3. Nuclear accumulation of SHIP1 mutants derived from AML patients leads to increased proliferation of leukemic cells. (United States)

    Nalaskowski, Marcus M; Ehm, Patrick; Rehbach, Christoph; Nelson, Nina; Täger, Maike; Modest, Kathrin; Jücker, Manfred


    The inositol 5-phosphatase SHIP1 acts as negative regulator of intracellular signaling in myeloid cells and is a tumor suppressor in myeloid leukemogenesis. After relocalization from the cytoplasm to the plasma membrane SHIP1 terminates PI3-kinase mediated signaling processes. Furthermore, SHIP1 is also found in distinct puncta in the cell nucleus and nuclear SHIP1 has a pro-proliferative function. Here we report the identification of five nuclear export signals (NESs) which regulate together with the two known nuclear localization signals (NLSs) the nucleocytoplasmic shuttling of SHIP1. Mutation of NLSs reduced the nuclear import and mutation of NESs decreased the nuclear export of SHIP1 in the acute myeloid leukemia (AML) cell line UKE-1. Interestingly, four SHIP1 mutants (K210R, N508D, V684E, Q1153L) derived from AML patients showed a nuclear accumulation after expression in UKE-1 cells. In addition, overexpression of the AML patient-derived mutation N508D caused an increased proliferation rate of UKE-1 cells in comparison to wild type SHIP1. Furthermore, we identified serine and tyrosine phosphorylation as a molecular mechanism for the regulation of nucleocytoplasmic shuttling of SHIP1 where tyrosine phosphorylation of distinct residues i.e. Y864, Y914, Y1021 reduces nuclear localization, whereas serine phosphorylation at S933 enhances nuclear localization of SHIP1. In summary, our data further implicate nuclear SHIP1 in cellular signaling and suggest that enhanced accumulation of SHIP1 mutants in the nucleus may be a contributory factor of abnormally high proliferation of AML cells. Copyright © 2017. Published by Elsevier Inc.

  4. Der Einfluss von sozialer Ungleichheit und kulturellen Unterschieden auf die Wahrnehmung von finanziellen und Arbeitsplatzrisiken: Überlegungen zur Risikogesellschaft


    Abbott, David; Quilgars, Deborah; Jones, Anwen


    Der vorliegende Artikel beruht auf Daten einer Studie, die sich mit der Frage beschäftigt, wie verschiedene soziale und kulturelle Gruppen die Risiken von Einkommens- und Arbeitsplatzverlust wahrnehmen und darauf reagieren. Autoren wie LASH, DOUGLAS und LUPTON betonten die Bedeutung von Gruppenzugehörigkeit und sozialen Kategorien für die Strukturierung der Reaktionsweisen auf verschiedene Risikoarten. Sie sprechen daher lieber von Risikokulturen als von der Risikogesellschaft. Trotzdem erken...

  5. Regulation of Trib2 by an E2F1-C/EBPα feedback loop in AML cell proliferation

    DEFF Research Database (Denmark)

    Rishi, Loveena; Hannon, Maura; Salomè, Mara


    α (C/EBPα)-p42, occurs in acute myeloid leukemia (AML), resulting in the perturbation of cell cycle and apoptosis, emphasizing its importance in the molecular pathogenesis of AML. Here we show that E2F family members directly regulate Trib2 in leukemic cells and identify a feedback regulatory loop......The loss of regulation of cell proliferation is a key event in leukemic transformation, and the oncogene tribbles (Trib)2 is emerging as a pivotal target of transcription factors in acute leukemias. Deregulation of the transcription factor E2F1, normally repressed by CCAAT enhancer-binding protein...... for E2F1, C/EBPα, and Trib2 in AML cell proliferation and survival. Further analyses revealed that E2F1-mediated Trib2 expression was repressed by C/EBPα-p42, and in normal granulocyte/macrophage progenitor cells, we detect C/EBPα bound to the Trib2 promoter. Pharmacological inhibition of the cell cycle...

  6. Functional analysis of P-glycoprotein and multidrug resistance associated protein related multidrug resistance in AML-blasts. (United States)

    Brügger, D; Herbart, H; Gekeler, V; Seitz, G; Liu, C; Klingebiel, T; Orlikowsky, T; Einsele, H; Denzlinger, C; Bader, P; Niethammer, D; Beck, J F


    Despite the high effectiveness of various P-glycoprotein (P-gp) modulating substances in vitro their clinical value e.g. for combination treatment of acute myelogenous leukemias (AML) remains still unclear. This might be explainable by recent findings that other factors than P-gp (e.g. the multidrug resistance associated protein (MRP)) may also be involved in clinical occurring drug resistance. To study P-gp and MRP mediated MDR in AML blasts from patients with relapses at the functional level we measured rhodamine 123 (RHO) efflux in combination with a P-gp specific (SDZ PSC 833) or a MRP specific (MK571) modulator, respectively. Furthermore, direct antineoplastic drug action was monitored by determination of damaged cell fraction of a blast population using flow cytometry. We generally found strongly modulated RHO efflux by SDZ PSC 833 but slight RHO-efflux modulation by MK571 in blasts from relapsed states of AML expressing MDR1 or MRP mRNA at various levels. We could not demonstrate, though, significant PSC 833 or MK571 mediated modulation of the cytotoxic effects of etoposide. The results point to the possibility that combination of etoposide and a modulator might not improve responses to chemotherapy by targeting P-gp or MRP exclusively.

  7. Induced Mitogenic Activity in AML-12 Mouse Hepatocytes Exposed to Low-dose Ultra-Wideband Electromagnetic Radiation

    Directory of Open Access Journals (Sweden)

    P. B. Tchounwou


    Full Text Available Ultra–wideband (UWB technology has increased with the use of various civilian and military applications. In the present study, we hypothesized that low-dose UWB electromagnetic radiation (UWBR could elicit a mitogenic effect in AML-12 mouse hepatocytes, in vitro. To test this hypothesis, we exposed AML-12 mouse hepatocytes, to UWBR in a specially constructed gigahertz transverse electromagnetic mode (GTEM cell. Cells were exposed to UWBR for 2 h at a temperature of 23°C, a pulse width of 10 ns, a repetition rate of 1 kHz, and field strength of 5-20 kV/m. UWB pulses were triggered by an external pulse generator for UWBR exposure but were not triggered for the sham exposure. We performed an MTT Assay to assess cell viability for UWBR-treated and sham-exposed hepatocytes. Data from viability studies indicated a time-related increase in hepatocytes at time intervals from 8-24 h post exposure. UWBR exerted a statistically significant (p < 0.05 dose-dependent response in cell viability in both serum-treated and serum free medium (SFM -treated hepatocytes. Western blot analysis of hepatocyte lysates demonstrated that cyclin A protein was induced in hepatocytes, suggesting that increased MTT activity after UWBR exposure was due to cell proliferation. This study indicates that UWBR has a mitogenic effect on AML-12 mouse hepatocytes and implicates a possible role for UWBR in hepatocarcinoma.

  8. Solution structure of a DNA mimicking motif of an RNA aptamer against transcription factor AML1 Runt domain. (United States)

    Nomura, Yusuke; Tanaka, Yoichiro; Fukunaga, Jun-ichi; Fujiwara, Kazuya; Chiba, Manabu; Iibuchi, Hiroaki; Tanaka, Taku; Nakamura, Yoshikazu; Kawai, Gota; Kozu, Tomoko; Sakamoto, Taiichi


    AML1/RUNX1 is an essential transcription factor involved in the differentiation of hematopoietic cells. AML1 binds to the Runt-binding double-stranded DNA element (RDE) of target genes through its N-terminal Runt domain. In a previous study, we obtained RNA aptamers against the AML1 Runt domain by systematic evolution of ligands by exponential enrichment and revealed that RNA aptamers exhibit higher affinity for the Runt domain than that for RDE and possess the 5'-GCGMGNN-3' and 5'-N'N'CCAC-3' conserved motif (M: A or C; N and N' form Watson-Crick base pairs) that is important for Runt domain binding. In this study, to understand the structural basis of recognition of the Runt domain by the aptamer motif, the solution structure of a 22-mer RNA was determined using nuclear magnetic resonance. The motif contains the AH(+)-C mismatch and base triple and adopts an unusual backbone structure. Structural analysis of the aptamer motif indicated that the aptamer binds to the Runt domain by mimicking the RDE sequence and structure. Our data should enhance the understanding of the structural basis of DNA mimicry by RNA molecules.

  9. Exchange Transfusion and Leukapheresis in Pediatric Patients with AML With High Risk of Early Death by Bleeding and Leukostasis. (United States)

    Creutzig, Ursula; Rössig, Claudia; Dworzak, Michael; Stary, Jan; von Stackelberg, Arend; Wössmann, Wilhelm; Zimmermann, Martin; Reinhardt, Dirk


    The risk of early death (ED) by bleeding/leukostasis is high in patients with AML with hyperleukocytosis (>100,000/μl). Within the pediatric AML-BFM (Berlin-Frankfurt-Münster) 98/04 studies, emergency strategies for these children included exchange transfusion (ET) or leukapheresis (LPh). Risk factors for ED and interventions performed were analyzed. Two hundred thirty-eight of 1,251 (19%) patients with AML presented with hyperleukocytosis; 23 of 1,251 (1.8%) patients died of bleeding/leukostasis. ED due to bleeding/leukostasis was highest at white blood cell (WBC) count >200,000/μl (14.3%). ED rates were even higher (20%) in patients with FAB (French-American-British) M4/M5 and hyperleukocytosis >200,000/μl. Patients with WBC >200,000/μl did slightly better with ET/LPh compared to those without ET/LPh (ED rate 7.5% vs. 21.2%, P = 0.055). Multivariate WBC >200,000/μl was of strongest prognostic significance for ED (P(χ(2) ) rate due to bleeding/leukostasis and is recommended at WBC >200,000/μl, and in FAB M4/M5 even at lower WBC. © 2015 Wiley Periodicals, Inc.

  10. The TEL-AML1 fusion protein of acute lymphoblastic leukemia modulates IRF3 activity during early B-cell differentiation. (United States)

    de Laurentiis, A; Hiscott, J; Alcalay, M


    The t(12;21) translocation is the most common genetic rearrangement in childhood acute lymphoblastic leukemia (ALL) and gives rise to the TEL-AML1 fusion gene. Many studies on TEL-AML1 describe specific properties of the fusion protein, but a thorough understanding of its function is lacking. We exploited a pluripotent hematopoietic stem/progenitor cell line, EML1, and generated a cell line (EML-TA) stably expressing the TEL-AML1 fusion protein. EML1 cells differentiate to mature B-cells following treatment with IL7; whereas EML-TA display an impaired differentiation capacity and remain blocked at an early stage of maturation. Global gene expression profiling of EML1 cells at different stages of B-lymphoid differentiation, compared with EML-TA, identified the interferon (IFN)α/β pathway as a primary target of repression by TEL-AML1. In particular, expression and phosphorylation of interferon-regulatory factor 3 (IRF3) was decreased in EML-TA cells; strikingly, stable expression of IRF3 restored the capacity of EML-TA cells to differentiate into mature B-cells. Similarly, IRF3 silencing in EML1 cells by siRNA was sufficient to block B-lymphoid differentiation. The ability of TEL-AML1 to block B-cell differentiation and downregulate the IRF3-IFNα/β pathway was confirmed in mouse and human primary hematopoietic precursor cells (Lin- and CD34+ cells, respectively), and in a patient-derived cell line expressing TEL-AML1 (REH). Furthermore, treatment of TEL-AML1 expressing cells with IFNα/β was sufficient to overcome the maturation block. Our data provide new insight on TEL-AML1 function and may offer a new therapeutic opportunity for B-ALL.

  11. Ein überfälliger Dialog. Wie Frauen- und Geschlechterforschung und Soziologie miteinander ins Gespräch kommen können

    Directory of Open Access Journals (Sweden)

    Heike Kahlert


    Full Text Available Die Monographie von Brigitte Aulenbacher zum Zusammenhang von Rationalisierung, Geschlecht und Gesellschaft ist in gegenstandsbezogener und methodologischer Hinsicht ambitioniert, überzeugend und lesenswert. Die Studie stellt eine solide, manchmal auch etwas zu weitschweifige und detailreiche Grundlage für weiterführende Diskussionen zwischen der (sozialwissenschaftlichen Frauen- und Geschlechterforschung und der Soziologie, genauer der Gesellschaftstheorie in zeitdiagnostischer Perspektive, Arbeits-, Industrie-, Organisations- und Techniksoziologie, dar.

  12. SGN-CD33A: a novel CD33-targeting antibody-drug conjugate using a pyrrolobenzodiazepine dimer is active in models of drug-resistant AML. (United States)

    Kung Sutherland, May S; Walter, Roland B; Jeffrey, Scott C; Burke, Patrick J; Yu, Changpu; Kostner, Heather; Stone, Ivan; Ryan, Maureen C; Sussman, Django; Lyon, Robert P; Zeng, Weiping; Harrington, Kimberly H; Klussman, Kerry; Westendorf, Lori; Meyer, David; Bernstein, Irwin D; Senter, Peter D; Benjamin, Dennis R; Drachman, Jonathan G; McEarchern, Julie A


    Outcomes in acute myeloid leukemia (AML) remain unsatisfactory, and novel treatments are urgently needed. One strategy explores antibodies and their drug conjugates, particularly those targeting CD33. Emerging data with gemtuzumab ozogamicin (GO) demonstrate target validity and activity in some patients with AML, but efficacy is limited by heterogeneous drug conjugation, linker instability, and a high incidence of multidrug resistance. We describe here the development of SGN-CD33A, a humanized anti-CD33 antibody with engineered cysteines conjugated to a highly potent, synthetic DNA cross-linking pyrrolobenzodiazepine dimer via a protease-cleavable linker. The use of engineered cysteine residues at the sites of drug linker attachment results in a drug loading of approximately 2 pyrrolobenzodiazepine dimers per antibody. In preclinical testing, SGN-CD33A is more potent than GO against a panel of AML cell lines and primary AML cells in vitro and in xenotransplantation studies in mice. Unlike GO, antileukemic activity is observed with SGN-CD33A in AML models with the multidrug-resistant phenotype. Mechanistic studies indicate that the cytotoxic effects of SGN-CD33A involve DNA damage with ensuing cell cycle arrest and apoptotic cell death. Together, these data suggest that SGN-CD33A has CD33-directed antitumor activity and support clinical testing of this novel therapeutic in patients with AML.

  13. Azacitidine improves outcome in higher-risk MDS patients with chromosome 7 abnormalities: a retrospective comparison of GESMD and GFM registries. (United States)

    Díez-Campelo, María; Lorenzo, Jose I; Itzykson, Raphael; Rojas, Silvia M; Berthon, Céline; Luño, Elisa; Beyne-Rauzy, Odile; Perez-Oteyza, Jaime; Vey, Norbert; Bargay, Joan; Park, Sophie; Cedena, Teresa; Bordessoule, Dominique; Muñoz, Juan A; Gyan, Emmanuel; Such, Esperanza; Visanica, Sorin; López-Cadenas, Félix; de Botton, Stéphane; Hernández-Rivas, Jesús M; Ame, Shanti; Stamatoullas, Aspasia; Delaunay, Jacques; Salanoubat, Celia; Isnard, Françoise; Guieze, Romain; Pérez Guallar, Joan; Badiella, Llorenc; Sanz, Guillermo; Cañizo, Consuelo; Fenaux, Pierre


    Treatment with azacitidine (AZA) has been suggested to be of benefit for higher-risk myelodysplastic syndrome (HR-MDS) patients with chromosome 7 abnormalities (Abn 7). This retrospective study of 235 HR-MDS patients with Abn 7 treated with AZA (n = 115) versus best supportive care (BSC; n = 120), assessed AZA treatment as a time-varying variable in multivariable analysis. A Cox Regression model with time-interaction terms of overall survival (OS) at different time points confirmed that, while chromosome 7 cytogenetic categories (complex karyotype [CK] versus non-CK) and International Prognostic Scoring System risk (high versus intermediate-2) retained poor prognosis over time, AZA treatment had a favourable impact on OS during the first 3 years of treatment compared to BSC (Hazard ratio [HR] 0·5 P MDS and cytogenetic abnormalities involving chromosome 7, especially for those with CK. © 2018 John Wiley & Sons Ltd.

  14. Bakteriochlorophyllvorstufen und Pigment-Protein-Komplexe in Rhodospirillum rubrum ST3 und GN11


    Hammel, Jörg U.


    In der vorliegenden Arbeit wurden zwei Mutanten des Alpha-Proteobakteriums Rhodospirillum rubrum untersucht, die im Bakteriochlorophyll-Biosyntheseweg unterbrochen sind, um einen Beitrag zum genaueren Verständnis der Biosynthese dieser Moleküle und der einzelnen daran beteiligten Schritte zu liefern. Von den beiden Stämmen ST3 und GN11 wurden die ins Kulturmedium ausgeschiedenen Pigmente aufgereinigt und spektroskopisch analysiert. Ebenfalls wurden sowohl von ST3, als auch von GN11 die in int...

  15. Computerspielgewalt und Aggression: Längsschnittliche Untersuchung von Selektions- und Wirkungseffekten


    Staude-Müller, Frithjof


    Auf Grundlage sozialkognitiver Aggressionsmodelle wurde die Beziehung zwischen Computerspielgewohnheiten und der Aggressionsneigung sowie Verzerrungen in der sozialen Informationsverarbeitung untersucht. Dazu wurden 499 Schüler/innen weiterführender Schulen (6.-8. Kl. Gymnasium, Haupt- und Realschule) in zwei Erhebungen mit einem Intervall von einem Jahr befragt. Mit hierarchischen Regressionsanalysen wurden Wirkungs- und Selektionseffekte geprüft, wobei relevante Drittvariablen (Monitoring u...

  16. Zu den Grundlagen der visuellen Soziologie: Wahrnehmen und Sehen, Beobachten und Betrachten


    Bachleitner, Reinhard; Weichbold, Martin


    In diesem Beitrag werden die visuellen Modi des Wahrnehmens – das Sehen, Beobachten und Betrachten – in ihrem Wesen skizziert, und die doppelte Theorieabhängigkeit von Wahrnehmungsprozessen wird thematisiert. Dabei zeigt sich, dass mehrere offene methodologische und erkenntnistheoretische Fragen durch die Differenzierung des Wahrnehmungsvorgangs in drei Stufen (reines Sehen, kognitive Repräsentation, Transformation des Perzepts in Worte) sowie die Differenzierung der Wahrnehmungsmodi in jewei...

  17. Intermediale Synchronisation zwischen Volltext und Film und ihre Realisierung in Hybrideditionen


    Bülow, Gilles


    Diese Arbeit behandelt die theoretische Erfassung und prototypische Erzeugung komplexer Musterdokumente mit synchronisiertem »Volltext« und »Bewegtbild«. Dabei werden wesentliche Randbedingungen für die Dokumentengliederung ermittelt. Diese Randbedingungen erlauben es dann, unterhalb der Plattformebene (des »reinen« Buchs und des »reinen« Films) neue multimediale Hybrideditionen auf Basis elektronischer Publikationsformate als Ausgabeplattform »sinnvoll« zu generieren. Empirisch wird der F...

  18. Expression and prognostic value of hemopoietic cytokine receptors in acute myeloid leukemia (AML): implications for future therapeutical strategies. (United States)

    Graf, Michaela; Hecht, Karin; Reif, Susanne; Pelka-Fleischer, Renate; Pfister, Karin; Schmetzer, Helga


    Hemopoietic cytokines regulate hemopoietic cell functions via specific cell surface receptors. There is evidence to suggest, that those receptors (R) could play a role in leukemia with respect to cell differentiations and its regulation, prognosis, and pathobiology. Knowledge of individual cytokine receptor (CKR) profiles could provide new discoveries about CKR-supported therapeutic considerations. We have studied the expression of CKR on mononuclear bone marrow (BM) cells of 89 patients with acute myeloid leukemia (AML) at first diagnosis, three patients at relapse or with persisting AML and eight healthy probands by fluorescence-activated cell sorting (FACS) analysis using directly fluorescein-conjugated antibodies: CD114 (hG-CSF-R), CD116 (hGM-CSF-R), CD117 (hSCF-R), CD123 (hIL-3-R), CD130 (gp130subunit), CD135 (hFL-R). A case was defined as positive, if more than 20% of the cells expressed the regarding CKR. All investigated CKR were more frequently expressed in AML-samples than in healthy BM-samples, except CD130, which was only expressed on 5-6% of AML-blasts in all and with only one healthy BM-sample being CD130(+). Within the French-American-British (FAB) types we observed a maturation- and lineage (granulocytic/monocytic)-committed expression profile. Monocytic subtypes (FAB-type M4/M5) showed significantly more GM-CSF-R(+) (P = 0.001) and FL-R(+) (P = 0.001) and significantly less stem cell factor-R (SCF-R(+)) (P = 0.02) cases. Highest proportions of G-CSF-R(+) blasts were observed in FAB-type M3. In undifferentiated leukemias (FAB-type M1, M2) high amounts of SCF-R(+), IL-3-R(+), and FL-R(+) blasts could be detected. FL-R was the only CKR, which was positive in FAB-type M0 (n = 2). No differences in CKR-expression were detected between primary (p) and secondary (s). Separating our patient cohorts in cytogenetic risk groups we could detect a significant higher proportion of G-CSF-R(+) blasts in the cytogenetic good risk group than in the bad risk group (P

  19. Die Kunst des Intavolierens: Gebundenheit und Freiheit

    Directory of Open Access Journals (Sweden)

    Ring, Johannes


    Full Text Available A big part of 16th century keyboard repertory was intabulated vocal music; arrangements of motets, sets of masses and chansons. Marcant and sometimes little known examples show the different functions of intabulations: repertoire for the organists (liturgical function, music of delight and pedagogical functions. As a part of Ars Organistum intabulations were the basis of professional musical studies, learning to improvise organ music and to compose music. Masters like H. Scheidemann, the both Gabrielis, J. de Lublin, P. Philips, the both Cabezóns, some English and French anonym composers demonstrate that intabulations are much more than keyboard reductions - artful arrangements with their own life and character on the way to artful paraphrases. The intentions of the composers / arrangers in connection with the possibilities of the keyboard instruments definite the character and the step of transforming a vocal set in a (new piece of keyboard music.

    [de] Ein großer Teil des Musikrepertoires für Tasteninstrumente im 16. Jahrhundert bestand aus intavolierter Vokalmusik - Bearbeitungen von Motetten, Messsätzen und Chansons. Markante und teilweise wenig bekannte Beispiele zeigen verschiedene Funktionen der Intavolierungen. Zu nennen sind das Organistenrepertoire (liturgisches Umfeld, die Musik zur Erbauung und Unterhaltung und die pädagogische Funktion. Als Bestandteil der Ars Organistum waren Intavolierungen wichtig um professionell das Improvisieren von Musik und das Komponieren zu erlernen. Exemplarisch dokumentieren besonders H. Scheidemann, die beiden Gabrielis, J. de Lublin, P. Philips, die beiden Cabezóns und einige anonyme Komponisten aus England und Frankreich, dass ihre Kunst des Intavolierens weit über den Übertragungsmodus hinausgeht, bis hin zum virtuosen Arrangement und zur kunstvollen Paraphrase. Die Intentionen der Komponisten in Verbindung mit den Möglichkeiten der Tasteninstrumente pr

  20. Kommunikation und Lernen in partizipativen kulturellen und medialen Räumen

    Directory of Open Access Journals (Sweden)

    Elke Zobl


    Full Text Available Eine der interessantesten Transformationen in der Jugendkultur seit den 1990er-Jahren ist die steigende Zahl vor allem an Mädchen und jungen Frauen, die zu aktiven kulturellen Produzentinnen wurden. In diesem Artikel wird argumentiert, dass sie mit ihren eigenen kulturellen Produktionen und Netzwerken neue soziale und mediale Räume öffnen, die durch eine partizipative Kultur, selbst-organisiertes Lernen in informellen Kontexten und lokale, transnationale und virtuelle Vernetzung und Kommunikation geprägt sind. Ziel dieses Artikels ist es, das Kommunizieren und Lernen in partizipativen kulturellen (bzw. sozialen und medialen Räumen am Beispiel queer-feministischer Festivals – sogenannter „Ladyfeste“ – darzustellen und ihre Bedeutung in (medien-pädagogischen Kontexten zu diskutieren.One of the most interesting transformations in youth culture since the 1990s is the growing number of girls and young women as active cultural producers. By creating their own cultural productions and networks, this article argues, that they open up new cultural (i. e. social and media spaces which are characterized by a participatory culture, self-organised learning and local, transnational and virtual networks and communication. Taking the example of queer-feminist festivals (so called “Ladyfests”, the aim of this article is to discuss communication and learning in participatory cultural and media spaces and their meaning in the context of (media-pedagogy.

  1. PHP und MySQL der Web-Baukasten fur Einsteiger und Individualisten

    CERN Document Server

    Damaschke, Giesbert


    Sie haben schon eigene Webseiten gebaut und mochten diese nun mit Funktionen ausstatten, fur die Sie PHP und MySQL benotigen? Giesbert Damaschke zeigt Ihnen in diesem Buch, wie Sie das schaffen. Schritt fur Schritt erlernen Sie die benotigten Programmier- und Datenbankgrundlagen - immer im Rahmen von typischen dynamischen Anwendungen. So erheben und speichern Sie zum Beispiel mit Formularen Kontaktdaten, prufen Benutzereingaben, erstellen Menus, richten einen Besucherzahler ein, verschicken E-Mails mit PHP oder entwickeln sogar einen eigenen Blog. Alle Codebeispiele werden ausfuhrlich erklart,

  2. Wirkungen eines Bifidojoghurts mit Laktulose und eines konventionellen Joghurts auf Darmphysiologie und bakterielle Metaboliten als Risikomodulatoren der Kolonkarzinogenese sowie Darmflora und Blutlipide bei gesunden Erwachsenen


    Gerlach, Stefanie


    Hintergrund: Probiotische und synbiotische Milchprodukte zählen zu den "funktionellen Lebensmitteln", denen im Vergleich zu herkömmlichen Produkten ein gesundheitsfördernder Zusatznutzen zugeschrieben wird. Dabei wird diskutiert, ob die Gesundheit bereits gesunder Personen noch optimierbar ist, ob und in welcher Weise die Darmflora gezielt "günstig" modifiziert werden kann und/oder ob diese Manipulation zu messbaren gesundheitsfördernden Veränderungen metabolischer und systemischer Biomarker ...

  3. Editorial: Theoriebildung in Mediendidaktik und Wissensmanagement

    Directory of Open Access Journals (Sweden)

    Michael Kerres


    Full Text Available Das Internet trägt massgeblich zur Entstehung einer neuen Lern- und Wissenskultur bei und ist mittlerweile Gegenstand einer ganzen Reihe von Projekten in der Erziehungswissenschaft. So wird zum Beispiel der Frage nachgegangen, welche Möglichkeiten der Strukturierung und Gestaltung von Lernmaterialien am besten geeignet sind, um Lernprozesse anzuregen, wie die interpersonale Kommunikation im Internet durch didaktische Gestaltungsmassnahmen gefördert werden können oder wie die entfernte Betreuung von Lernenden über das Netz funktioniert. Zunehmend wird dabei auch der Übergang bedeutsam zwischen didaktisch aufbereiteten Lernangeboten, wie sie die Mediendidaktik traditionell beschäftigt, und dem Austausch von nicht didaktisch aufbereiteten Informationen in Organisationen, wie es im Bereich des Wissensmanagements diskutiert wird. In diesen Projekten werden vielfach Detailfragen behandelt, und isoliert, ohne Bezug zu grundlegenden Theoriefragen untersucht. Es mangelt an einer genuin mediendidaktischen Theoriediskussion, die einen übergreifenden Bezugsrahmen aus erziehungswissenschaftlicher Perspektive liefert. In der Vergangenheit ist die Mediendidaktik von Seiten einer «kritischen» Medienpädagogik zeitweise skeptisch beäugt und in ihrer Existenz grundlegend infrage gestellt worden. In der aktuellen Diskussion wird gerne auf lerntheoretische Ansätze zurückgegriffen, die Lernen als aktiven Vorgang der individuellen und kooperativen Wissenskonstruktion begreifen. Doch Wissens- und Lerntheorien ersetzen keine mediendidaktische Modell- und Theoriebildung, die Perspektiven für eine Gestaltung zukünftiger Lernwelten liefert und dabei zum Beispiel sowohl bildungstheoretische Überlegungen als auch Konzepte des instructional design einbezieht. In dem ersten Teil dieser Ausgabe geht es um theoretische Perspektiven der Mediendidaktik. So diskutiert der Artikel von Michael Kerres und Claudia de Witt den Beitrag der Positionen von Behaviorismus

  4. Symmetriebrechung und Emergenz in der Kosmologie. (United States)

    Mainzer, K.

    Seit der Antike wird der Aufbau des Universums mit einfachen und regulären (symmetrischen) Grundstrukturen verbunden. Diese Annahme liegt selbst noch den Standardmodellen der relativistischen Kosmologie zugrunde. Demgegenüber läßt sich die Emergenz neuer Strukturen von den Elementarteilchen über Moleküle bis zu den komplexen Systemen des Lebens als Symmetriebrechung verstehen. Symmetriebrechung und strukturelle Komplexität bestimmen die kosmische Evolution. Damit zeichnet sich ein fachübergreifendes Forschungsprogramm von Physik, Chemie und Biologie ab, in dem die Evolution des Universums untersucht werden kann.

  5. Die Ware Buch und die Philologie

    Directory of Open Access Journals (Sweden)

    Bernhard Hurch


    Full Text Available Die im 19. Jahrhundert sich verändernden Produktionsbedingungen für Druckwerke (Buchdruck, Satz, Papier, Bindung wirkten katalysierend auf die Fachkonstitution und Institutionalisierung der Philologien. Hier steht der tatsächliche Buchmarkt im Vordergrund der Darstellung, das Käuferpublikum und die Voraussetzungen des Vertriebs. Dazu gehören auch die Rezension als entstehende Textsorte und die rasch arbeitenden Rezensionsorgane. F.-R. Hausmann wurde in den letzten Jahren unentbehrlicher Mitarbeiter dieses im Rahmen des Grazer Schuchardt-Projekts "Netzwerk des Wissens" angesiedelten Ansatzes.

  6. Fluchen und Flamen, um ein Mann zu sein? Die Verknüpfung von Geschlecht und Sprache durch Vorurteile

    Directory of Open Access Journals (Sweden)

    Nicola Döring


    Full Text Available Die hier besprochene Monographie der Linguistin Anja Gottburgsen beschäftigt sich theoretisch und empirisch mit sprachbezogenen Geschlechterstereotypen, also mit unseren Vorstellungen darüber, ob und wie Männer und Frauen jeweils in spezifischer und distinkter Weise sprachlich kommunizieren. Im Theorieteil der Arbeit wird der aktuelle Stand der soziolinguistischen und sozialpsychologischen Diskussion zu Geschlecht, Sprachverhalten und Stereotypisierung kritisch referiert und die Bedeutung von sprachbezogenen Geschlechterstereotypen erläutert. Im empirischen Teil berichtet die Autorin die Ergebnisse von drei Fragebogen-Studien mit deutschsprachigen Studierenden. Es zeigt sich, dass bei Studierenden unabhängig von Geschlecht und Geschlechtsrollenorientierung stereotype Vorstellungen über das sprachliche Verhalten von Männern und Frauen verbreitet sind.

  7. [Das Bild und die Wahrnehmung der Stadt und der städtischen Gesellschaft im Hanseraum im Mittelalter und in der frühen Neuzeit] / Juhan Kreem

    Index Scriptorium Estoniae

    Kreem, Juhan


    Arvustus: Das Bild und die Wahrnehmung der Stadt und der städtischen Gesellschaft im Hanseraum im Mittelalter und in der frühen Neuzeit. hrsg. v. Roman Czaja. Torun, 2004. Torunis 2002. aastal toimunud konverentsi materjalid. Projekti "Pilt ja linn" raames ilmunud publikatsioonide loendit saab näha aadressil

  8. Diagnostik und Therapie der kutanen Androgenisierung im klimakterischen Übergang sowie in der Peri- und Postmenopause: Hirsutismus und Alopezie

    Directory of Open Access Journals (Sweden)

    Geisthövel F


    Full Text Available Die weibliche Androgenisierung umfasst ein weites Spektrum an heterogenen Dysfunktionen und Erkrankungen. Um die Therapieprinzipien des Hirsutismus sowie der Alopecia androgenetica während des klimakterischen Übergangs („menopausal transition“ [MT] und der Peri-/Postmenopause zu erfassen, ist es sinnvoll, sich auf eine Gruppe von androgenisierten Patientinnen zu beschränken, bei der die Haut pathogenetisch im Fokus liegt. Solch eine klar definierte Patientengruppe, die „funktionell kutane Androgenisierung“ (FCA, kann meist schon über die Diagnostikebene 1 (Screening-Ebene unseres Klassifikations-Algorithmus diagnostiziert werden. Der Ferriman-Gallwey-Index bzw. eine modifizierte Sinclair-Scale dienen zur Gradeinteilung von Hirsutismus bzw. Alopezie. Die ausgeprägte endokrine Dynamik während der MT ist hormondiagnostisch zu beachten. Wachsepilation und Lasertherapie sind vielfältig eingesetzte topischmechanische bzw. -physikalische Therapieverfahren. Eine topische Behandlung des Hirsutismus kann auch mit Eflornithin-Creme durchgeführt werden, die den Effekt einer Lasertherapie unterstützt. Minoxidil-Lösung gilt als Mittel der ersten Wahl bei der topischen Therapie der Alopecia androgenetica. Steroidale Präparate, welche aus der kontrazeptiven Kombination von Ethinylestradiol und antiandrogenen Gestagenen (AA bestehen, sind therapeutische Prinzipien bei androgenisierten Patientinnen in der MT, sie sind hingegen in der Postmenopause kontraindiziert. Die orale Einnahme von Spironolacton und/oder Finasterid, beides nicht-steroidale Antiandrogene, ist während der MT unter sicherer Kontrazeption und jene von Spironolacton für die Alopezie in der Postmenopause gut geeignet. Die Einnahme von Kombinationsprapäraten, welche die nicht-kontrazeptiven natürlichen Östrogene und AA enthalten, sind für die Behandlung der FCA bei Patientinnen indiziert, die zusätzlich unter klimakterischen und peri-/postmenopausalen Störungen leiden

  9. Struktur und Dynamik in der Netzwerkanalyse

    NARCIS (Netherlands)

    Trier, M.; Stegbauer, C.; Häußling, R.


    Die Methodik der sozialen Netzwerkanalyse (SNA) ist auf die quantitative Untersuchung von strukturellen Mustern in Graphen ausgerichtet. Die Analyse arbeitet gegenwärtig meist mit Daten aus einer einmaligen und kumulierten Erhebung der Netzwerkstruktur zu einem bestimmten Zeitpunkt. Diese

  10. Satellitenbewegung, band III: Natiirliche und gesteuerte bewegung. (United States)

    Jochim, E. F.


    Im dritten Band der Satellitenbewegung werden in fortlaufender Nummerierung einige für Untersuchungen der Bewegung der künstlichen Satelliten wichtige Grundlagen der Astrodynamik mit ausführlichen mathematischen Formelsystemen behandelt. Dazu zählen die unterschiedlichen Aspekte der Bewegung der natürlichen Himmelskörper, die Steuerung und Kontrolle von künstlichen Objekten, und insbesondere die für eine Satellitenbahnanalyse wichtigen physikalischen Beeinflussungen einer Satellitenbewegung. Mathematisch entscheidend ist die Wahl geeigneter Bahnparameter, die ein bestimmtes Bewegungsproblem widerspruchsfrei und singularitätenfrei zu behandeln gestatten. Für die Behandlung routinemäßiger Aufgabenstellungen der Satellitenbewegung, in erster Linie einer präzisen Bahnbestimmung und Bahnverbesserung, kann auf eine Fülle von lehrbuchartigen Monographien verwiesen werden, so dass diese Problematik in der vorliegenden Arbeit nur angedeutet werden soll.

  11. Riots ‒ Anmerkungen zu Begriff und Konzept

    Directory of Open Access Journals (Sweden)

    Dieter Rucht


    Full Text Available Ausgehend von sozialwissenschaftlichen Befunden werden zunächst ältere massenpsychologische Deutungen von riots zurückgewiesen. Die überwiegende Mehrzahl der im riot Aufbegehrenden entspricht nicht dem Typus entfremdeter und verängstigter Einzeltäter_innen. Zweitens benennt der Beitrag eine Reihe von Bedingungen für das Zustandekommen von riots. Drittens wird der Begriff ‚riot‘ in formaler Hinsicht näher bestimmt und einerseits von moderateren Formen des Protests, andererseits von geplanter und organisierter Gewalt (z. B. Terrorismus abgegrenzt. Abschließend wird die Frage des politischen Gehalts von riots und deren normativen Grundlagen erörtert.

  12. [Die baltischen Lande im Zeitalter der Reformation und Konfessionalisierung : Livland, Estland, Ösel, Ingermanland, Kurland und Lettgallen. Stadt, Land und Konfession 1500-1721. Teil 1.] / Jürgen Beyer

    Index Scriptorium Estoniae

    Beyer, Jürgen, 1965-


    Arvustus: Die baltischen Lande im Zeitalter der Reformation und Konfessionalisierung. Livland, Estland, Ösel, Ingermanland, Kurland und Lettgallen. Stadt, Land und Konfession 1500-1721. Teil 1. (Münster : Aschendorff, 2009)

  13. Matthias Asche, Werner Buchholz, Anton Schindling (Hrsg.): Die baltischen Lande im Zeitalter der Reformation und Konfessionalisierung. Livland, Estland, Ösel, Ingermanland, Kurland und Lettgallen. Stadt, Land und Konfession 1500-1721. Tl. 2, Münste

    Index Scriptorium Estoniae

    Wittram, Heinrich, 1931-


    Arvustus: Die baltischen Lande im Zeitalter der Reformation und Konfessionalisierung : Livland, Estland, Ösel, Ingermanland, Kurland und Lettgallen : Stadt, Land und Konfession 1500-1721. Teil 2. Münster, 2010

  14. Benjamin Ortmeyer: Mythos und Pathos statt Logos und Ethos, Zu den Publikationen führender Erziehungswissenschaftler in der NS-Zeit: Eduard Spranger, Herman Nohl, Erich Weniger und Peter Petersen, Weinheim / Basel: Beltz 2009 [Rezension


    Zimmer, Hasko


    Rezension von: Benjamin Ortmeyer: Mythos und Pathos statt Logos und Ethos, Zu den Publikationen führender Erziehungswissenschaftler in der NS-Zeit: Eduard Spranger, Herman Nohl, Erich Weniger und Peter Petersen, Weinheim / Basel: Beltz 2009, 606 S.

  15. The humanities and innovation; Geisteswissenschaften und Innovationen

    Energy Technology Data Exchange (ETDEWEB)

    Meyer-Krahmer, F.; Lange, S. [eds.] [Fraunhofer-Institut fuer Systemtechnik und Innovationsforschung (ISI), Karlsruhe (Germany)


    The book discusses the concept and process of innovation from the perspective of linguistics, historical sciences, and philosophy. Inter-disciplinary relations become evident when it comes to research into human consciousness and behaviour, dealing with language and texts, or the growing significance of the historical sciences with respect to topical developments in technology and the economy. The cross-disciplinary discourse between the various disciplines of the humanities, natural sciences, technology and the social sciences, and between science, industry and public administration has revealed a new playing field for cross-disciplinary dialogue and cooperative action that may be rewarding. The book discusses aspects such as the innovative potential of the humanities, or their possible contributions to innovation, their capabilities to generate innovative changes in the way of thinking, to prepare the ground for innovation, strengthen innovative abilities, and on the other hand to hold aloof and keep a watchful eye on innovation. (orig./CB) [German] Das Buch beschaeftigt sich mit Innovationen aus sprachwissenschaftlicher, historischer und philosophischer Sicht. Querbezuege werden deutlich, wenn es um die Erforschung von Bewusstsein und Verhalten, dem Umgang mit Sprache und Texten oder die wachsende Bedeutung der historischen Wissenschaften fuer die aktuelle technologische und wirtschaftliche Entwicklung geht. Das Gespraech ueber Fachgrenzen hinweg zwischen den verschiedenen Disziplinen der Geisteswissenschaften, der Natur-, Technik- und Sozialwissenschaften und zwischen Wissenschaft, Industrie und oeffentlicher Verwaltung hat Aufgaben deutlich gemacht, die die Zusammenarbeit lohnen. In diesem Band wird diskutiert, welches Innovationspotential die Geisteswissenschaften bieten, wie diese zu Innovationen beitragen, Innovationen im Denken hervorbringen, Vorarbeiten fuer Innovationen leisten, die Innovationsfaehigkeit staerken und die kritische Distanz zu Innovationen

  16. Neue Technologien und Erziehung/Bildung

    Directory of Open Access Journals (Sweden)

    Norbert Meder


    Full Text Available Es wird gezeigt, dass Computertechnologie zur pädagogischen Aufgabe wird, weil es sich um eine Kulturtechnik handelt. Ausgehend vom Begriff der Bildung als Ausbildung eines Verhältnisses zu mir selbst, zu anderen und zur Welt wird Computertechnologie als Problemlösungsautomat, Sprachentwicklungsmaschine, Simulationsmaschine, Kommunikationsmaschine, Bildschirmgestaltungsmaschine, Schlüsselloch und Superzeichenmaschine analysiert. Die Analyse zeigt, daß Computertechnologie ein neues Bildungsideal erforderlich macht: Den Sprachspieler. Der Sprachspieler kennt sein doppelt reflexives Verhältnis zu sich selbst, zu anderen und zur Welt und beherrscht so das Spiel mit der Sprache zur Ausübung von Macht und Gewalt in der Informationsgesellschaft. Der Text geht in folgenden Schritten vor: Zunächst werden mit den Begriffen "Kulturtechnik" und "Bildung" die Prinzipien der Analyse bestimmt. Anschließend wird eine Sachanalyse der Computertechnologie durchgeführt und die gefundenen Eigenschaften jeweils in Relation zum Kulturtechnik- und Bildungsbegriff gesetzt. Computer technology becomes a challenge for education if it is understood as a cultural technology. Starting with the term bildung as the formation of relations to my self, to others and the world, computer technology is analysed as problem solving machine, language development machine, simulation machine, communication machine, screen design machine, keyhole, and super sign machine. It is shown, that computertechnology reqiures a new ideal for bildung: the language player. The language player knows his double reflective relation to his self, to others and the world and thus rules the game with language that is used to excercise power and force in the information society. The text argues in the following steps: At first the principles of the analyses are defined with the terms cultural technology and bildung. Susequently, computer technology is analysed. The identified qualities are finally

  17. Medien als Lernform und die Trimediale Redaktion

    Directory of Open Access Journals (Sweden)

    Wolf Hilzensauer


    Full Text Available Der vorliegende Artikel beschreibt ein Konzept für eine handlungsorientierte Medienpädagogik im Bildungsbereich. Im Mittelpunkt steht dabei die SO!-Campusredaktion, die als Methode für expansives Lernen die Möglichkeit bietet, unabhängig von Thema oder Medium die Verantwortung für den Lernprozess in die Hände der Lernenden zu legen. Der Dokumentation von Reflexion über den Lernprozess wird dabei eine besondere Bedeutung zugesprochen. Gleichzeitig werden unterschiedliche mediale Gestaltungsmöglichkeiten (Audio/Radio, Video/Fernsehen und Zeitung – sowohl als Print- als auch als Onlinemedium vorgestellt, die durch das Konzept BYOD – bring your own device – auch einfach und niederschwellig im Bildungskontext umsetzbar sind. Dadurch ergeben sich innovative Möglichkeiten, einen Lernprozess sichtbar zu machen und gleichzeitig eine Grundlage für eine alternative Leistungsbeurteilung anzubieten. Die SO!-Campusredaktion wird derzeit an der Pädagogischen Hochschule Salzburg in Kooperation mit dem Communitysender FS1 und der Radiofabrik entwickelt und erprobt. Community Medien nehmen als MedienpartnerInnen eine bedeutende Stellung ein: Durch ihren offenen Zugang zu Know How und Equipment sowie durch die Möglichkeit, Medienproduktionen über die verfügbaren Distibutionskanäle (Radiofrequenz oder Sendeplatz einer breiten Bevölkerung zugänglich zu machen, gewinnt die Medienpädagogik einen wichtigen Mehrwert in ihrer schulischen und außerschulischen Arbeit. (Dieser Artikel knüpft an den Artikel "BYOD, Smartphonefilme und webbasierte Videoschnittprogramme" der Medienimpulse, Ausgabe 2/2014, an.

  18. Polen, Deutschland, die EU und Russland


    Wilkiewicz, Zbigniew


    Besonders seit dem EU-Beitritt Polens ist es um die deutsch-polnischen Beziehungen nicht besonders gut bestellt. In den vergangenen Jahren hat man sich in erster Linie an bilateralen Konflikten abgearbeitet und keine gemeinsame Europapolitik betrieben. Im Beitrag wird diese Entwicklung rekonstruiert und danach gefragt, ob es angesichts einer solchen Entwicklung Aussichten auf die Wiederherstellung der deutsch-polnischen Interessengemeinschaft gibt oder die Interessen beider Staaten so stark d...

  19. Professionelle Literaturrecherche und -verwaltung im Web [Praxisbericht


    Schaffert, Sandra


    In diesem Beitrag werden Hinweise für eine professionelle Literaturrecherche und -verwaltung im World Wide Web gegeben. Dazu werden für die pädagogische Ausbildung und Forschung einschlägige Literaturdatenbanken genannt, insbesondere solche, die kostenlos zu nutzen sind. Außerdem werden Tipps für clevere Recherchen sowie eine kurze Übersicht über Web-Werkzeuge zur Verwaltung von bibliografischen Angaben gegeben. (DIPF/Orig.)

  20. Ontologische und epistemologische Grundlagen qualitative Forschung


    Vasilachis de Gialdino, Irene


    Dieser Beitrag zielt auf das Herzstück qualitativer Forschung, indem gezeigt wird, dass es – aus der Perspektive einer Epistemologie des "gewussten" Subjekts – erforderlich ist, zunächst deren ontologische und dann deren epistemologische Grundlagen neu zu überdenken. Hierzu zeichne ich in einem ersten Schritt den Weg von einer Epistemologie des "bewussten" Subjekts hin zu einer Epistemologie des "gewussten" Subjekts nach, die ich als neuen (und nicht exklusiven) Weg des Wissens vorschlage. Da...

  1. Generation Y: Arbeitsbezogene Erwartungen und affektives Commitment


    Giry, Nathalie


    Die Erwartungen der Generation Y zu kennen, ist wichtig für Unternehmen, die Leistungsträger aus dieser Generation langfristig binden wollen. Die affektive Bindung der Generation Y gegenüber einer Organisation, der Zusammenhang zwischen der Erfüllung arbeitsbezogener Erwartungen und affektivem Commitment sowie der Fluktuationsneigung der Generation Y werden empirisch überprüft. Die Generation Y hat hohe Erwartungen an Unternehmenswerte und Unternehmenskultur. Es wurden Zusammenhänge zwischen ...

  2. Climate and transportation; Klima und Verkehr

    Energy Technology Data Exchange (ETDEWEB)

    Fabian, P. [Muenchen Univ. (Germany). Lehrstuhl fuer Bioklimatologie und Immissionsforschung


    This short contribution discusses emissions of the transportation sector, i.e. the global problem of carbon dioxide emissions and the regional ecological problem of nitric oxide, VOC and CO photosmog emissions. Reduction strategies are discussed. (RHM) [Deutsch] Im vorliegenden, kurzen Beitrag wird auf die Emissionen des Verkehrs, die Emissionen von CO{sub 2} - ein globales Klimaproblem - sowie die Emission von NO{sub x}, VOCs und CO-Photosmog als regionals Umwelt- und Klimaproblem eingegangen. Abschliessend werden Reduktionsstrategien dieskutiert. (RHM)

  3. Entscheidungsprozesse und Partizipation in der Stadtentwicklung Dresdens


    Schmidt-Lerm, Susanne


    Untersucht wurde die Auseinandersetzung um das Autobahnbauvorhaben A 17 Dresden - Prag zwischen 1990 und 1995 als ein Beispiel der Stadtentwicklung Dresdens. Seit 1935 als Reichsautobahn ins Sudetenland geplant, sollte dieses Verkehrsprojekt nach 1990 als „Lückenschluß im europäischen Autobahnnetz“ umgesetzt werden. Angesichts des hohen Konfliktpotentials erlangte der Fall überregionale Aufmerksamkeit und Beispielcharakter für die neuen Bundesländer. Die Kontroverse gipfelte im ersten Bürgere...

  4. Kolloide in externen elektrischen und magnetischen Feldern


    Zhao, Jinyu


    Kolloide spielen eine wichtige Rolle in der Forschung. In vielen Anwendungsgebieten, beispielsweise Optik, Mikro- und Nanoelektronik, Mikrofluidik, Automobilindustrie, Mineralölindustrie, dienen sie sowohl als Testsubstanzen als auch "Werkzeug", um grundlegende Vorgänge zu erforschen. In der Grundlagenforschung dienen kolloidale Suspensionen als Modelle für atomare und molekulare Systeme. In der vorliegenden Arbeit habe ich Suspensionen aus festen Kolloiden (auch als Partikel bezeichnet) in e...

  5. Kurz zum Klima: Schiefergas und Fracking


    Triebswetter, Ursula; Lippelt, Jana


    Das Verfahren zur Gewinnung von Erdgas aus wenig durchlässigem Gestein, das in den USA erfundene und dort bereits weit verbreitete »Hydraulic Fracturing«, kurz Fracking, ist aus Umweltgründen umstritten. Der Beitrag skizziert zunächst die Technologie des Fracking, umreißt dann die weltweiten Lagerstätten und beschreibt die umweltpolitische Problematik. Abschließend wird die aktuelle Situation in Deutschland dargestellt.

  6. Time to redefine PD? Introductory statement of the MDS Task Force on the definition of Parkinson's disease. (United States)

    Berg, Daniela; Postuma, Ronald B; Bloem, Bastiaan; Chan, Piu; Dubois, Bruno; Gasser, Thomas; Goetz, Christopher G; Halliday, Glenda M; Hardy, John; Lang, Anthony E; Litvan, Irene; Marek, Kenneth; Obeso, José; Oertel, Wolfgang; Olanow, C Warren; Poewe, Werner; Stern, Matthew; Deuschl, Günther


    With advances in knowledge disease, boundaries may change. Occasionally, these changes are of such a magnitude that they require redefinition of the disease. In recognition of the profound changes in our understanding of Parkinson's disease (PD), the International Parkinson and Movement Disorders Society (MDS) commissioned a task force to consider a redefinition of PD. This review is a discussion article, intended as the introductory statement of the task force. Several critical issues were identified that challenge current PD definitions. First, new findings challenge the central role of the classical pathologic criteria as the arbiter of diagnosis, notably genetic cases without synuclein deposition, the high prevalence of incidental Lewy body (LB) deposition, and the nonmotor prodrome of PD. It remains unclear, however, whether these challenges merit a change in the pathologic gold standard, especially considering the limitations of alternate gold standards. Second, the increasing recognition of dementia in PD challenges the distinction between diffuse LB disease and PD. Consideration might be given to removing dementia as an exclusion criterion for PD diagnosis. Third, there is increasing recognition of disease heterogeneity, suggesting that PD subtypes should be formally identified; however, current subtype classifications may not be sufficiently robust to warrant formal delineation. Fourth, the recognition of a nonmotor prodrome of PD requires that new diagnostic criteria for early-stage and prodromal PD should be created; here, essential features of these criteria are proposed. Finally, there is a need to create new MDS diagnostic criteria that take these changes in disease definition into consideration. © 2014 International Parkinson and Movement Disorder Society.

  7. RANK und RANKL - Vom Knochen zum Mammakarzinom

    Directory of Open Access Journals (Sweden)

    Sigl V


    Full Text Available RANK („Receptor Activator of NF-κB“ und sein Ligand RANKL sind Schlüsselmoleküle im Knochenmetabolismus und spielen eine essenzielle Rolle in der Entstehung von pathologischen Knochenveränderungen. Die Deregulation des RANK/RANKL-Systems ist zum Beispiel ein Hauptgrund für das Auftreten von postmenopausaler Osteoporose bei Frauen. Eine weitere wesentliche Funktion von RANK und RANKL liegt in der Entwicklung von milchsekretierenden Drüsen während der Schwangerschaft. Dabei regulieren Sexualhormone, wie zum Beispiel Progesteron, die Expression von RANKL und induzieren dadurch die Proliferation von epithelialen Zellen der Brust. Seit Längerem war schon bekannt, dass RANK und RANKL in der Metastasenbildung von Brustkrebszellen im Knochengewebe beteiligt sind. Wir konnten nun das RANK/RANKLSystem auch als essenziellen Mechanismus in der Entstehung von hormonellem Brustkrebs identifizieren. In diesem Beitrag werden wir daher den neuesten Erkenntnissen besondere Aufmerksamkeit schenken und diese kritisch in Bezug auf Brustkrebsentwicklung betrachten.

  8. Finanzkrise, Sozialkrise und ungleiche Entwicklung in Südkorea und Thailand

    DEFF Research Database (Denmark)

    Schmidt, Johannes Dragsbæk


    Zehn Jahre ist es inzwischen her, dass die Finanzkrisen in Südostasien, Russland und Lateinamerika die Weltwirtschaft erschütterten. Angesichts dieses "Jubiläums" und der aktuellen US-Finanzkrise ist es Zeit für eine Bestandsaufnahme: Lektionen gelernt? Drei Fragestellungen stehen im Mittelpunkt...

  9. Methoden der Kommunikations- und Mediengeschichte: die Wechselwirkung unterschiedlicher Verfahren als Spezifikum der Kommunikations- und Mediengeschichte

    NARCIS (Netherlands)

    Hemels, J.; Averbeck-Lietz, S.; Klein, P.; Meyen, M.


    Dieser Beitrag verfolgt zwei Ziele: Einerseits wird beabsichtigt, nicht his-torisch geschulte Kommunikationswissenschaftler mit Grundlagen und Praxis kommunikationswissenschaftlicher Forschung vertraut zu ma-chen. Andererseits wird für ein Zusammenspiel zwischen führenden For-schungsansätzen und

  10. Alexander Kratochvil. Aufbruch und Rückkehr: Ukrainische und tschechische Prosa im Zeichen der Postmoderne.

    Directory of Open Access Journals (Sweden)

    Marko Pavlyshyn


    Full Text Available Alexander Kratochvil. Aufbruch und Rückkehr: Ukrainische und tschechische Prosa im Zeichen der Postmoderne. [Venturing Forth and Coming Back: Ukrainian and Czech Prose in the Context of Postmodernity.] Berlin: Kulturverlag Kadmos, 2013. 311 pp. Bibliography. Index. Paper.

  11. Characterization of children with FLT3-ITD acute myeloid leukemia: a report from the AIEOP AML-2002 study group. (United States)

    Manara, E; Basso, G; Zampini, M; Buldini, B; Tregnago, C; Rondelli, R; Masetti, R; Bisio, V; Frison, M; Polato, K; Cazzaniga, G; Menna, G; Fagioli, F; Merli, P; Biondi, A; Pession, A; Locatelli, F; Pigazzi, M


    Recurrent molecular markers have been routinely used in acute myeloid leukemia (AML) for risk assessment at diagnosis, whereas their post-induction monitoring still represents a debated issue. We evaluated the prognostic value and biological impact of minimal residual disease (MRD) and of the allelic ratio (AR) of FLT3-internal-tandem duplication (ITD) in childhood AML. We retrospectively screened 494 children with de novo AML for FLT3-ITD mutation, identifying 54 harboring the mutation; 51% of them presented high ITD-AR at diagnosis and had worse event-free survival (EFS, 19.2 versus 63.5% for low ITD-AR, <0.05). Forty-one percent of children with high levels of MRD after the 1st induction course, measured by a patient-specific real-time-PCR, had worse EFS (22.2 versus 59.4% in low-MRD patients, P<0.05). Next, we correlated these parameters with gene expression, showing that patients with high ITD-AR or persistent MRD had characteristic expression profiles with deregulated genes involved in methylation and acetylation. Moreover, patients with high CyclinA1 expression presented an unfavorable EFS (20.3 versus 51.2% in low CyclinA1 group, P<0.01). Our results suggest that ITD-AR levels and molecular MRD should be considered in planning clinical management of FLT3-ITD patients. Different transcriptional activation of epigenetic and oncogenic profiles may explain variability in outcome among these patients, for whom novel therapeutic approaches are desirable.

  12. Relationship between the non-motor items of the MDS-UPDRS and Quality of Life in patients with Parkinson's disease

    NARCIS (Netherlands)

    Skorvanek, Matej; Rosenberger, Jaroslav; Minar, Michal; Grofik, Milan; Han, Vladimir; Groothoff, Johan W.; Valkovic, Peter; Gdovinova, Zuzana; van Dijk, Jitse P.


    The Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) is a newly developed comprehensive tool to assess Parkinson's disease (PD), which covers a wider range of non-motor PD manifestations than the original UPDRS scale. The aim of this study was to assess the relationship

  13. CMS MDS 3.0 Section M Skin Conditions in Long-term Care: Pressure Ulcers, Skin Tears, and Moisture-Associated Skin Damage Data Update. (United States)

    Ayello, Elizabeth A


    The purpose of this learning activity is to provide information about the updates to the Centers for Medicare & Medicaid Services (CMS) MDS 3.0 Section M, Skin Conditions documentation in long-term care. This continuing education activity is intended for physicians, physician assistants, nurse practitioners, and nurses with an interest in skin and wound care. After participating in this educational activity, the participant should be better able to:1. Explain the use of the CMS MDS 3.0 tool for documenting skin problems in long-term care.2. Demonstrate examples of proper documentation for specific skin problems. This manuscript reviews some of the key parts of the October 2016 revised Long-term Care Resident Assessment Instrument manual for Minimum Data Set (MDS) 3.0 Section M Skin Conditions. It also reports the Centers for Medicare & Medicaid's publicly reported frequency data in long-term care for selected items on the MDS 3.0 Section M Skin Conditions. Percentages and trends of pressure ulcers/injuries, skin tears, and moisture-associated skin damage are assessed.

  14. A clinical trial of supervised exercise for adult inpatients with acute myeloid leukemia (AML) undergoing induction chemotherapy☆ (United States)

    Alibhai, Shabbir M.H.; O’Neill, Sara; Fisher-Schlombs, Karla; Breunis, Henriette; Brandwein, Joseph M.; Timilshina, Narhari; Tomlinson, George A.; Klepin, Heidi D.; Culos-Reed, S. Nicole


    Patients with acute myeloid leukemia (AML) receiving induction chemotherapy (IC) were enrolled in a supervised exercise intervention to determine safety, feasibility, and efficacy. Physical fitness measures, quality of life (QOL) and fatigue were assessed using standardized measures at baseline, post-induction, and post first consolidation. Retention was excellent, the intervention was safe, and efficacy estimates suggested benefits in physical fitness and QOL outcomes. Exercise is a safe, promising intervention for improving fitness and QOL in this patient population. These results provide a foundation for a randomized trial to better understand the impact of exercise during IC on clinically important outcomes. PMID:22726923

  15. A clinical trial of supervised exercise for adult inpatients with acute myeloid leukemia (AML) undergoing induction chemotherapy. (United States)

    Alibhai, Shabbir M H; O'Neill, Sara; Fisher-Schlombs, Karla; Breunis, Henriette; Brandwein, Joseph M; Timilshina, Narhari; Tomlinson, George A; Klepin, Heidi D; Culos-Reed, S Nicole


    Patients with acute myeloid leukemia (AML) receiving induction chemotherapy (IC) were enrolled in a supervised exercise intervention to determine safety, feasibility, and efficacy. Physical fitness measures, quality of life (QOL) and fatigue were assessed using standardized measures at baseline, post-induction, and post first consolidation. Retention was excellent, the intervention was safe, and efficacy estimates suggested benefits in physical fitness and QOL outcomes. Exercise is a safe, promising intervention for improving fitness and QOL in this patient population. These results provide a foundation for a randomized trial to better understand the impact of exercise during IC on clinically important outcomes. Copyright © 2012 Elsevier Ltd. All rights reserved.

  16. A randomized comparison of daunorubicin 90 mg/m2 vs 60 mg/m2 in AML induction

    DEFF Research Database (Denmark)

    Burnett, A. K.; Russell, N. H.; Hills, R. K.


    Modifying induction therapy in acute myeloid leukemia (AML) may improve the remission rate and reduce the risk of relapse, thereby improving survival. Escalation of the daunorubicin dose to 90 mg/m(2) has shown benefit for some patient subgroups when compared with a dose of 45 mg/m(2), and has been...... = .15). In an exploratory subgroup analysis, there was no subgroup that showed significant benefit, although there was a significant interaction by FLT3 ITD mutation. This trial is registered at as #ISRCTN55675535....

  17. Review: Michael Kerres & Reinhard Keil-Slawik (Hrsg.) (2005). Hochschulen im digitalen Zeitalter: Innovationspotenziale und Strukturwandel


    Hoidn, Sabine


    In dem vorliegenden Kongressband setzen sich fünfunddreißig internationale Expertinnen und Experten aus Wissenschaft und Praxis mit Möglichkeiten und Rahmenbedingungen des Einsatzes von Informations- und Kommunikationstechnologien in Hochschulen auseinander. Die Beiträge adressieren aktuelle und zukünftige Herausforderungen, denen sich Hochschulen zu stellen haben, und präsentieren einen bunten Strauß an (bisher) erfolgreichen Projekten und Praxiserfahrungen. Infolge knapper werdender Ressour...

  18. Aussteigen aus dem Rechtsextremismus: Foto-Praxis, bildwissenschaftliche Analyse und Ausstellungsarbeit als Methoden individueller Reflexion und des wissenschaftlichen und (sozialpädagogischen Kompetenzerwerbs

    Directory of Open Access Journals (Sweden)

    Ulrike Pilarczyk


    Full Text Available Der Beitrag zeigt die medienpädagogischen und bildwissenschaftlichen Dimensionen eines zeitlich und thematisch gestaffelten Projektes auf. Ausgangspunkt war das in den Jahren 2009/10 von der Organisation EXIT-Deutschland in Berlin mit Aussteigern/-innen aus der rechtsextremen Szene initiierte Fotoprojekt «Lebensbilder». Die im Rahmen biografisch orientierter, medien- und sozialpädagogischer Fallarbeit entstandenen Fotos wurden als Prozess individueller Bilderzeugung und als Mittel zur Reflexion der jeweiligen Lebenssituation der Aussteiger(innen verstanden und eingesetzt. Eine Ausstellung schloss diese erste Phase des hier beschriebenen Projektes ab. Dem Wunsch folgend, die praktischen Erfahrungen aus der Arbeit mit Fotos wissenschaftlich überprüfen zu lassen, wurden in den Jahren 2011 und 2012 mit Studierenden am erziehungswissenschaftlichen Institut der TU Braunschweig die «Lebensbilder» zunächst einer wissenschaftlichen Bildanalyse unterzogen und anschliessend in einem gestalterisch-interpretativen Projekt durch die Studierenden zu einer Ausstellung weiterentwickelt.

  19. Die Werte der Wertvermittler - Berufliches Rollenselbstverständnis und Weltanschauung von Journalistinnen und Journalisten

    Directory of Open Access Journals (Sweden)

    Andy Kaltenbrunner


    Full Text Available Der Beitrag analysiert professionelles Selbstverständnis, Weltanschauungen und ethische Überzeugungen von Journalistinnen und Journalisten in Österreich. Auf Basis aktueller Befragungen und Studien wird die Grundstruktur des journalistischen Wertesystems skizziert und der Zusammenhang mit täglicher Berichterstattung. Der Beitrag diskutiert mögliche Konsequenzen für Zukunft des Journalismus und Qualität der Öffentlichkeit. The article focuses on the professional values, political views and ethical beliefs of Austrian journalists. Based on recent surveys we outline the basic structure of the journalistic value system in Austria and the interdependence of these values and actual reporting and we discuss possible consequences for the future of journalism as a profession and for the quality of the public sphere.

  20. Hinkelbeinchen und "little chicken's leg": deutsche und amerikanische Idiome als kommunikative Textsorten-Problematik

    Directory of Open Access Journals (Sweden)

    Martin Wierschin


    Full Text Available Als Marin Luther 1522 seine Übersetzung des Neuen Testaments nach der griechischen Edition des Erasmus von Rotterdam abschloß, hatte er dabei zwar mit größtem Sprachgefühl nicht nur dem deutschen, sondem auch dem idiomatischen 'logos' des Griechischen "auf das Maul" gesehen. Aber er mußte in seinem "Sendbrief vom Dolmetschen" 1530 dennoch zugeben, daß selbst er - zusammen mit seinen beiden Assistenten Melanchthon und Aurogallus - sehr oft zwei bis vier Wochen lang nach einem einzigen idiomatisch treffenden Wort zu suchen hatte. Damit wird von einem eminenten Kronzeugen, nämlich vom Schöpfer des protestantischen 'Hausbuches' Lutherbibel und vom eigentlichen Begründer einer einheitlichen deutschen Schrift­ sprache, samt ihrer sprach- und literargeschichtlich wirkungsmächtigen Idiomatik, die Schwierigkeit und Problematik idiomatischer Äquivalenzen und Transferenzen zwischen den Einzelsprachen verbürgt.

  1. Neue Medien in der Lehrerausbildung. Zu angemessenen (und unangemessenen Zielen und Inhalten des Lehramtsstudiums

    Directory of Open Access Journals (Sweden)

    Sigrid Blömeke


    Full Text Available In vier Schritten wird dem Verhältnis von Lehrerausbildung und neuen Medien nachgegangen. Zunächst werden grundsätzliche medienpädagogische Aufgaben der Lehrerausbildung herausgearbeitet, bevor das Ausbildungsprofil ihrer ersten und zweiten Phase in den Blick genommen wird. Ausgangspunkt der Theoriebildung sind professions- und institutionentheoretische Ansätze, die auf die neuen Medien bezogen werden; Konkretisierungen erfolgen an Beispielen aus der Germanistik, der Anglistik, der Geschichte und der Mathematik. Anschliessend wird der Erwerb medienpädagogischer Kompetenz durch zukünftige Lehrerinnen und Lehrer von dem Erwerb basaler Medienkompetenz als eines Elements von Allgemeinbildung abgegrenzt. Zum Schluss werden Konsequenzen für die strukturelle Gestaltung der Lehrerausbildung gezogen.

  2. Studie: Die Generation Y und deren organisatorische Implikationen


    Klein, Helmut


    Die vorliegende Studie betrifft die Gen. Y und ihre spezifischen Anforderungen an die Unternehmensorganisation. Im Ergebnis einer durchgeführten Befragung ist festzuhalten, dass die Gen. Y die Kernkompetenzen eines Managers verstärkt einfordert und eine hohe Betreuungsintensität verlangt. Dies hat Auswirkungen auf die Führungsspanne, Planung und Kontrolle von Aufgaben, die Gestaltung der vertikalen und horizontalen Prozesse sowie die Zusammensetzung von Teamarbeitsformen. Projektarbeit sowie ...

  3. Beginn und Dosisanpassung einer intensivierten konventionellen Insulintherapie (ICT beim Erwachsenen

    Directory of Open Access Journals (Sweden)

    Lohr R


    Full Text Available Eine intensivierte Insulintherapie (ICT ist die Behandlung der Wahl bei Diabetes mellitus Typ 1 und auch bei vielen Menschen mit insulinpflichtigem Typ-2-Diabetes. Bei Therapiebeginn müssen individuell Insuline ausgewählt und die richtige Dosierung festgelegt werden. Im weiteren Verlauf ist dann die Anpassung der Insulintherapie an besondere Alltagssituationen wie Sport oder akute Erkrankungen vorrangig. Eine gute Patientenschulung und eine gute Zusammenarbeit zwischen Betroffenem und Behandlerteam sind entscheidend, um diese komplizierte Therapie erfolgreich umzusetzen.

  4. Informationsdesign von Bildungsportalen : Struktur und Aufbau netzbasierter Bildungsressourcen


    Panke, Stefanie


    Sowohl Unternehmen als auch Bildungseinrichtungen, Verlage, politische Organisationen, Verbände, Interessengruppen und Privatpersonen nutzen das Internet, um Informationen zu verbreiten. Die Varianz an Akteuren, Adressaten und Botschaften spiegelt sich wider in einem wachsenden Spektrum an Web-Genres: Suchmaschine, E-Commerce-Auftritt und Online-Zeitung teilen sich die Aufmerksamkeit der Leser unter anderem mit privaten Weblogs und kollaborativen Wissenssammlungen wie der Enzyklopädie Wikiped...

  5. Molekulare Systematik und Evolution der Spezies der Familie Arthrodermataceae (Dermatophyten)


    Gräser, Yvonne


    Dermatophyten sind keratinophile Pilze, d.h. sie besiedeln und infizieren die Haut und ihre Anhangsgebilde (Haare, Nägel) bei Mensch und Tier. Die derzeit häufigsten durch Dermatophyten hervorgerufenen Infektionen sind die Onychomykose, Tinea pedis, Tinea capitis und Tinea corporis. Da Antimykotika nicht bei alle Erregern von Dermatophytosen gleich wirksam sind, sollte im Vordergrund einer Behandlung zunächst die korrekte Erregerdifferenzierung stehen. Konventionell erfolgt diese Differenzier...

  6. Spurenstoffuntersuchungen zur Bildung und Ausbreitung von Wassermassen im subpolaren Nordatlantik


    Hildebrandt, Hauke


    In der vorliegenden Arbeit wurde ein umfangreicher Spurenstoffdatensatz aus dem subpolaren Nordatlantik erstellt und ausgewertet, der Tritium-, Helium- und Neon- sowie O-18-Messungen umfaßt. Das Hauptaugenmerk galt dabei der Bildung und Ausbreitung der tiefen Wassermassen und deren Variabilität auf Zeitskalen von einigen Jahren. Anhand von Tracermittelwerten, die mit Hilfe eines optimierten Interpolationsverfahrens gewonnen wurden, konnte gezeigt werden, daß die konvektive Neubildung de...

  7. Aufgabenbezogene Differenzierung und Entwicklung des verbalen Selbstkonzepts im Anfangsunterricht


    Lipowsky, Frank; Kastens, Claudia; Lotz, Miriam; Faust, Gabriele


    Die vorliegende Studie untersucht, wie sich aufgabenbezogene Differenzierung im Deutschunterricht auf die Entwicklung des verbalen Selbstkonzepts von Erst- und Zweitklässlern (Lesen und Schreiben) auswirkt. Die untersuchte Stichprobe setzt sich aus 735 Schülern des ersten Schuljahres zusammen, die 38 Klassen an staatlichen und privaten Grundschulen besuchen und die bis zum Ende des zweiten Schuljahres in ihrer Entwicklung untersucht wurden. Die Ergebnisse zeigen sowohl einen indirekten als au...

  8. Märkte und Macht der Internetkonzerne: Konzentration - Konkurrenz - Innovationsstrategien


    Dolata, Ulrich


    In diesem Aufsatz, der auf einer systematischen Auswertung von Geschäftsberichten, Dokumenten, verfügbarem empirischem Material, Literatur und Presseberichten basiert, werden die Konzentrationsprozesse auf den wesentlichen Internetmärkten so- wie die Expansions- und Innovationsstrategien der fünf führenden Konzerne Google, Facebook, Apple, Amazon und Microsoft analysiert. Die Befunde, die der Text vorstellt, sind von einer Dezentralisierung der Markt- und Demokratisierung der Innovationsproze...

  9. Arbeitszeiten von Professorinnen und Professoren in Deutschland 2016


    Weihs, Claus; Hernández Rodríguez, Tanja; Doeckel, Maximilian; Marty, Christoph; Wormer, Holger


    In dieser Studie werden belastbare Prognoseintervalle der wöchentlichen Gesamtarbeitszeit von Universitätsprofessorinnen und -professoren aus Daten einer Umfrage aus dem Jahre 2016 und a-priori Informationen aus früheren Studien bestimmt. Neben der Gesamtarbeitszeit werden auch Teilarbeitszeiten zum Beispiel für Lehre und Forschung ermittelt. Die Ergebnisse von frequentistischer und Bayesianischer Analyse werden verglichen. Aus den gültigen Fragebögen von aktiven Vollzeit arbeitenden Universi...

  10. Umfrageforschung: Entscheidungsgrundlage für Politik und Wissenschaft



    "Der vorliegende Tagungsband dokumentiert die Beiträge der wissenschaftlichen Tagung 'Umfrageforschung - Entscheidungsgrundlage für Politik und Wissenschaft', die am 30. Juni und 1. Juli 2011 gemeinsam vom Statistischen Bundesamt, dem ADM Arbeitskreis Deutscher Markt- und Sozialforschungsinstitute e.V. und der Arbeitsgemeinschaft Sozialwissenschaftlicher Institute e.V. (ASI) in Wiesbaden durchgeführt wurde." (Autorenreferat). Inhaltsverzeichnis: Christian König, Matthias Stahl, Erich Wiegand:...

  11. Reputationsorientiertes Themen- und Issues-Management : Konzeption, Regelbetrieb, Weiterentwicklung


    Fahrenbach, Christian


    Die Dissertation untersucht, wie Organisationen ein reputationsorientiertes Themen- und Issues-Management aufbauen, betreiben und weiterentwickeln können. Dazu wird das operative Modell des Issues Managements mit dem strategischen Zielkonstrukt Reputation verbunden. Zu Beginn der Arbeit beschreiben zwei Theorie-Kapitel ausführlich Relevanz und die Steuerung von Reputation und im Issues Management. Auf dieser Basis wird ein praxisorientiertes integriertes Modell entwickelt. Es beschreibt da...

  12. Azacitidine in combination with intensive induction chemotherapy in older patients with acute myeloid leukemia: The AML-AZA trial of the Study Alliance Leukemia. (United States)

    Müller-Tidow, C; Tschanter, P; Röllig, C; Thiede, C; Koschmieder, A; Stelljes, M; Koschmieder, S; Dugas, M; Gerss, J; Butterfaß-Bahloul, T; Wagner, R; Eveslage, M; Thiem, U; Krause, S W; Kaiser, U; Kunzmann, V; Steffen, B; Noppeney, R; Herr, W; Baldus, C D; Schmitz, N; Götze, K; Reichle, A; Kaufmann, M; Neubauer, A; Schäfer-Eckart, K; Hänel, M; Peceny, R; Frickhofen, N; Kiehl, M; Giagounidis, A; Görner, M; Repp, R; Link, H; Kiani, A; Naumann, R; Brümmendorf, T H; Serve, H; Ehninger, G; Berdel, W E; Krug, U


    DNA methylation changes are a constant feature of acute myeloid leukemia. Hypomethylating drugs such as azacitidine are active in acute myeloid leukemia (AML) as monotherapy. Azacitidine monotherapy is not curative. The AML-AZA trial tested the hypothesis that DNA methyltransferase inhibitors such as azacitidine can improve chemotherapy outcome in AML. This randomized, controlled trial compared the efficacy of azacitidine applied before each cycle of intensive chemotherapy with chemotherapy alone in older patients with untreated AML. Event-free survival (EFS) was the primary end point. In total, 214 patients with a median age of 70 years were randomized to azacitidine/chemotherapy (arm-A) or chemotherapy (arm-B). More arm-A patients (39/105; 37%) than arm-B (25/109; 23%) showed adverse cytogenetics (P=0.057). Adverse events were more frequent in arm-A (15.44) versus 13.52 in arm-B, (P=0.26), but early death rates did not differ significantly (30-day mortality: 6% versus 5%, P=0.76). Median EFS was 6 months in both arms (P=0.96). Median overall survival was 15 months for patients in arm-A compared with 21 months in arm-B (P=0.35). Azacitidine added to standard chemotherapy increases toxicity in older patients with AML, but provides no additional benefit for unselected patients.

  13. Infectious Complications in Children With Acute Myeloid Leukemia and Down Syndrome: Analysis of the Prospective Multicenter Trial AML-BFM 2004. (United States)

    Hassler, Angela; Bochennek, Konrad; Gilfert, Julia; Perner, Corinna; Schöning, Stefan; Creutzig, Ursula; Reinhardt, Dirk; Lehrnbecher, Thomas


    Children with acute myeloid leukemia (AML) and Down syndrome have high survival rates with intensity-reduced chemotherapeutic regimens, although the optimal balance between dose intensity and treatment toxicity has not been determined. We, therefore, characterized infectious complications in children with AML and Down syndrome treated according to AML-BFM 2004 study ( NCT00111345; amended 2006 for Down syndrome with reduced intensity). Data on infectious complications were gathered from the medical records in the hospital where the patient was treated. Infectious complications were categorized as fever without identifiable source (FUO), or as microbiologically or clinically documented infections. A total of 157 infections occurred in 61 patients (60.5% FUO, 9.6% and 29.9% clinically and microbiologically documented infections, respectively). Almost 90% of the pathogens isolated from the bloodstream were Gram-positive bacteria, and approximately half of them were viridans group streptococci. All seven microbiologically documented episodes of pneumonia were caused by viruses. Infection-related mortality was 4.9%, and all three patients died due to viral infection. Our data demonstrate that a reduced-intensity chemotherapeutic regimen in children with AML and Down syndrome is still associated with high morbidity. Although no patient died due to bacteria or fungi, viruses were responsible for all lethal events. Future studies, therefore, have to focus on the impact of viruses on morbidity and mortality of patients with AML and Down syndrome. © 2016 Wiley Periodicals, Inc.

  14. Safety and efficacy of the CD95-ligand inhibitor asunercept in transfusion-dependent patients with low and intermediate risk MDS. (United States)

    Boch, Tobias; Luft, Thomas; Metzgeroth, Georgia; Mossner, Maximilian; Jann, Johann-Christoph; Nowak, Daniel; Meir, Franziska La; Schumann, Christiane; Klemmer, Jennifer; Brendel, Susanne; Fricke, Harald; Kunz, Claudia; Weiß, Christel; Hofmann, Wolf-Karsten; Nolte, Florian


    In low risk MDS, increased apoptosis of erythroid progenitors mediated via CD95 (Fas) activation has been described to result in peripheral cytopenia. Blockade of the CD95 system can improve erythropoiesis in MDS. Asunercept (APG101) is a fusion protein consisting of the extracellular domain of human CD95 and the Fc domain of human IgG1 blocking the interaction between CD95 and its ligand. Here we report on results from a phase I study in 20 transfusion-dependent low and intermediate risk MDS patients treated with intravenous asunercept (EudraCT 2012-003027-37). Primary objectives were safety and tolerability as well as pharmacodynamic effects. Secondary objectives were hematologic improvement, incidence and time to leukemic progression as well as overall survival. Frequency and severity of adverse events were in range of what could be expected in a patient cohort comprising of elderly MDS patients. Two patients experienced a serious adverse event with a suspected relationship to asunercept. The incidence of disease progression was low. In the 20 patients a decrease of the transfusion need from a mean of 10,8 (±5,1) pRBCs during the 12 weeks treatment phase to a mean of 10,0 (±4,2) pRBCs at the end of the study was observed. In conclusion, asunercept was well tolerated and showed efficacy in transfusion-dependent low and intermediate risk MDS patients. Further clinical investigation is warranted, particularly in combination with erythropoiesis stimulating agents (ESAs). Copyright © 2018. Published by Elsevier Ltd.

  15. Age-related changes of healthy bone marrow cell signaling in response to growth factors provide insight into low risk MDS. (United States)

    Kornblau, Steven M; Cohen, Aileen C; Soper, David; Huang, Ying-Wen; Cesano, Alessandra


    Single Cell Network Profiling (SCNP) is a multiparametric flow cytometry-based assay that quantifiably and simultaneously measures changes in intracellular signaling proteins in response to in vitro extracellular modulators at the single cell level. Myelodysplastic syndrome (MDS) is a heterogeneous clonal disorder of hematopoietic stem cells that occurs in elderly subjects and is characterized by dysplasia and ineffective hematopoiesis. The functional responsiveness of MDS bone marrow (BM) hematopoietic cells, including functionally distinct myeloid and erythroid precursor subsets, to hematopoietic growth factors (HGF) and the relationship of modulated signaling to disease characteristics is poorly understood. SCNP was used first to examine the effects of age on erythropoietin (EPO) and granulocyte colony stimulating factor (GCSF)-induced signaling in myeloid, nucleated red blood cells (nRBC), and CD34 expressing cell subsets in healthy BM (n = 15). SCNP was then used to map functional signaling profiles in low risk (LR) MDS (n = 7) for comparison to signaling in samples from healthy donors and to probe signaling associations within clinically defined subgroups. In healthy BM samples, signaling responses to HGF were quite homogeneous (i.e., tightly regulated) with age-dependent effects observed in response to EPO but not to GCSF. Despite the relatively small number of samples assayed in the study, LR MDS could be classified into distinct subgroups based on both cell subset frequency and signaling profiles. As a correlate of underlying genetic abnormalities, signal transduction analyses may provide a functional and potentially clinically relevant classification of MDS. Further evaluation in a larger cohort is warranted. © 2013 Clinical Cytometry Society.

  16. Die Landschaft in der Geschichte, in der Kultur, in der Kunts und in der Stadtplanung: theoretische Annahmen und Erfahrungen

    Directory of Open Access Journals (Sweden)

    Mario Coletta


    Full Text Available Das vorgeschlagene Thema hat das Ziel, dem Konzept der Landschaft eine neue Definition zu geben. Sie soll nicht nur als Umhuellung des staedtischen und laendlichen Territoriums gesehen werden, das besiedelt und produktiv ist, zivilisiet und natuerlich belassen, sondern wie ein lebender Koerper, wenn auch nicht bei bester Gesundheit, der trotz seines Altes noch den vielen Veraenderungen standhaelt. Veraenderungen durch Naturkatatrophen herforgerufen, und besonders durch die vielen Wunden die das Werk der Menschen ihm zugefuegt hat. Als lebendes Wesen leidet die Landschaft und freut sich in guten Zeiten, kleidert sich lieber arm, aber schicklich, als reich und anmassend: Zeuge guter und schlechter Haushaltsfuehrung, jedoch Erbe einer Geschichte die sie erhebt, die Geschichte, Literatur, Ausdruecke der Kunts, kreative Planung beseelt hat. All das ist zusammengefasst in dem Wort "Kultur", die es verdient hat, erworben zu werden, vertieft und den naeschsten Generationen weitergegeben, moeglicherweise noch bereichert von dem, das die heutige Kultur ausarbeiten kann, auch auf dem Weg der Stadtplanung.

  17. Game-Review: Trilogie Mass Effect 1, 2 und 3

    Directory of Open Access Journals (Sweden)

    Karl H. Stingeder


    Full Text Available Karl Stingeder hat als Spieletester die Science Fiction Trilogie Mass Effect (1,2 und 3 rezensiert. Er berichtet von der inneren Vielfalt und dem spannenden Gameplay. Tauchen Sie ein in eine Welt, die ihnen eine lange Spielzeit garantiert und genießen Sie die Pracht dieser Kunstwerke.

  18. Klare Regeln - effiziente und effektive FMEA-Anwendung


    Schloske, Alexander


    Der Vortrag beschreibt klare Regeln zur effizienten und effektiven FMEA-Anwendung. - Denkmodelle für die verschiedenen FMEA-Arten (System-FMEA, Konstruktions-FMEA, Prozess-FMEA) - Anwendungsbereiche und FMEA-Planung - Strukturierung von FMEAs - Funktionen, Produktmerkmale und Prozessmerkmale - Risikoanalyse - Maßnahmendefinition - Risikobewertung - Präsentation von FMEAs - FMEA als "lebendes Dokument".

  19. Der Heilige Geist und die Realisierung des Glaubens in der ...

    African Journals Online (AJOL)

    29. Juli 2016 ... der Sprache bis hin zu den kulturellen und religiösen. Zeichensystemen, muss von dem Einzelnen empfangen und angeeignet werden. Kommunikation, auch die religiöse, verwirklicht sich ausschließlich in der Spannung von geschichtlicher Abhängigkeit und Transformation der überlieferten Gehalte im ...

  20. Die Inquisition und ihre Wahrnehmung im Alten Reich

    Directory of Open Access Journals (Sweden)

    Alexandra Kohlhöfer


    Full Text Available Rezension von: Tribunal der Barbaren? Deutschland und die Inquisition in der Frühen Neuzeit, hg. von Albrecht Burckhardt und Gerd Schwerhoff unter Mitwirkung von Dieter R. Bauer (Konflikte und Kultur – Historische Perspektiven 25, Konstanz, München: UVK-Verl.-Ges. 2012, 450 S., ISBN 978-3-86764-371-9

  1. Biologisch-dynamische Forschung zwischen "wissenschaftlicher Weltsicht" und "Ideologie"


    Eysel, Georg


    Der Beitrag zeigt den Konflikt zwischen "wertefreier" Wissenschaft und "ganzheitlicher" Forschung auf. Ein Zusammenspiel bio-dynamischer Forschung und der Anthroposophie mit anderen Disziplinen könnte einen Beitrag zu einem neuen Wissenschaftsbegriff mit umfassender Weltanschauung leisten. Dialog, Verständnis, Toleranz, Offenheit, kritisches Hinterfragen und Mut zur sinnvollen Anpassung sind dafür notwendige Schritte.

  2. Anmerkungen zur Methode einer theologischen Wirtschafts- und Sozialethik


    Mack, Elke


    "Moderne theologische Wirtschafts- und Sozialethik sollte im Rahmen der wissenschaftstheoretischen Schritte 'Analyse, Synthese, Operationalisierung' erfolgen. Die christliche Wirtschafts- und Sozialethik erfüllt bei diesem Zuschnitt den Anspruch einer modernen theologischen Gerechtigkeitstheorie, die erstens ihr hermeneutisches Vorverständnis hinreichend klärt und analytisch an Problemstellungen herangeht, die zweitens auf der Basis eines hypothetischen Konsenses aller Betroffener zu normativ...

  3. Die Verbesserung von Tiergesundheit und Wohlergehen der Tiere in Maststierbetrieben

    DEFF Research Database (Denmark)

    Kirchner, Marlene


    europäisches Forschungsprojekt, das die Integration des Tierwohlergehens in die Nahrungsqualitätskette zum Thema hatte. Das Projekt trug den Bedenken der Gesellschaft und Wünschen des Marktes Rechnung und entwickelte zuverlässige Systeme für die Kontrolle landwirtschaftlicher Betriebe und die...

  4. Konflikt und Kooperation bei der Wassernutzung in Mittelasien

    NARCIS (Netherlands)

    Wegerich, K.


    In Mittelasien sind Mensch, Natur und Wirtschaft auf das Wasser zweier Flusssysteme angewiesen: des Syr Darja im Norden und des Amu Darja im Süden. Beide Ströme sind in hohem Maße zur Stromgewinnung und landwirtschaftlichen Bewässerung erschlossen. Die Nutzung des Wassers birgt erhebliches Potential

  5. Blogs und Journalismus – Konkurrenz oder Ergänzung? – Das Verhältnis von Blogs und Journalismus in Deutschland

    Directory of Open Access Journals (Sweden)

    Saskia Leidinger


    Full Text Available Mit der Frage, ob „Blogs und Journalismus - Konkurrenz oder Ergänzung“ sind, beschäftigt sich Saskia Leidinger in dem gleichnamigen Essay über „das Verhältnis von Blogs und Journalismus in Deutschland“. In vergleichender Perspektive richtet die Autorin ihr Hauptaugenmerk auf die Arbeitsweise sowie die Eigen- und Fremdwahrnehmung von Bloggern und Journalisten, um Gemeinsamkeiten und Unterschiede herauszustellen und ihre je spezifische Funktion innerhalb der der heutigen Informationsgesellschaft einzugrenzen.

  6. Rasterelektronenmikroskopische und immunhistochemische Untersuchungen am Eileiter vom Schwein während Zyklus und Trächtigkeit


    Mayer, Judith


    In der vorliegenden Arbeit wurden zum einen mit Hilfe des Rasterelektronenmikroskops die morphologischen Veränderungen des Eileiterepithels und zum anderen die Expression hypophysärer wachstums- und proliferationsfördernder Hormone und ihrer Rezeptoren immunhistochemisch und mit der Reverse Transkriptase (RT)-PCR sowohl im Verlauf des Zyklus als auch der Trächtigkeit analysiert. Hierfür wurden, von 24 Schweinen der Deutschen Landrasse, die drei Abschnitte des Eileiters (Infundibulum, Ampulle,...

  7. Krieg und Literatur War and Literature

    Directory of Open Access Journals (Sweden)

    Elfi N. Theis


    Full Text Available Schreiben gegen Krieg und Gewalt heißt der Band 19 der Schriften-Reihe des Erich-Maria-Remarque-Archivs, in dem es um Ingeborg Bachmann und die deutschsprachige Literatur 1945-1980 geht. Der Band enthält die Beiträge zu einem Symposion, das am 14.-15. Januar 2005 an der Universität Nottingham stattgefunden hat. Im Mittelpunkt stand die Frage, welche Strategien im Umgang mit Nationalsozialismus, Holocaust, zweitem Weltkrieg, Kaltem Krieg oder Vietnamkrieg und auch dem deutschen Kolonialismus bei Bachmann und anderen deutschsprachigen Autoren zu finden sind. Anlass zur Tagung war die in Wien und Salzburg konzipierte Ausstellung Schreiben gegen den Krieg: Ingeborg Bachmann, 1926-1973. In insgesamt dreizehn Beiträgen wird im vorliegenden Band die literarische Auseinandersetzung mit dem Thema Gewalt und Krieg beleuchtet.Volume 19 of the series published by the Erich-Maria-Remarque Archive is entitled “Writing against War and Violence” (“Schreiben gegen Krieg und Gewalt” and approaches Ingeborg Bachmann and German language literature from 1945 to 1980. The volume contains contributions based on a symposium that took place at the University of Nottingham on January 14-15, 2005. Central to the symposium was the question as to which strategies Bachmann and other German language authors utilized in their approach to National Socialism, the Holocaust, the Second World War, the Cold War, or the Vietnam War, as well as German colonialism. The impetus for the conference was the exhibition Writing Against the War: Ingeborg Bachmann, 1926-1973 conceived in Vienna and Salzburg. In the volume at hand, thirteen contributions in total illuminate literary confrontations with the themes of war and violence.

  8. Acute myeloblastic leukemia with minimal myeloid differentiation (FAB AML-M0): a study of eleven cases. (United States)

    Sempere, A; Jarque, I; Guinot, M; Palau, J; García, R; Sanz, G F; Gomis, F; Pérez-Sirvent, M L; Senent, L; Sanz, M A


    The main clinical, morphological, cytochemical, immunological features and therapy results of eleven patients diagnosed as acute myeloblastic leukemia M0 (AML-M0) are reported here. There were no clinical characteristics, abnormalities on physical examination or initial laboratory parameters that distinguished these eleven patients. Bone marrow aspirates were hypocellular in four patients. The leukemic cells were undifferentiated by light microscopy and myeloperoxidase (MPO) and/or Sudan Black B (SBB) stains were negative in all cases. Myeloid differentiation antigens were present on the leukemic cells of all eleven patients, whereas B and T cell markers were clearly negative except for CD4 and CD7 antigens. Whatever the treatment employed survival was very short. Eight of the eleven patients were treated and two achieved complete remission (CR) but only one of them is alive in continuous CR. Our results like those previously reported, suggest that AML-M0 patients have a very poor prognosis with standard induction therapies and should perhaps be considered for experimental therapeutic approaches.

  9. Geotourism and Sustainability: The Kızılcahamam – Çamlıdere Geopark Case

    Directory of Open Access Journals (Sweden)

    M. Sercan Gürsay


    Full Text Available Today, geotourism is one of the popular types of special interest tourism. On the other hand, poorly managed tourism can have some negative economic, environmental and socio-cultural impacts on destinations. Therefore, all types of tourism should be managed with a sustainable approach. The concept of sustainability, which had been first introduced in 1987, in the Report entitled “Our Common Future” as a fundamental of development, and has three dimensions of social, economic and environmental aspects. The purpose of this study is to evaluate sustainable tourism practices in Kızılcahamam - Çamlıdere Geopark. In this context, local stakeholders’ opinion on the importance of sustainable tourism in the management of the geopark area is determined. The qualitative method was used in this study. Data were collected through review of the related literature, observation and in-depth interviews. As a result of the study, physical and legal deficiencies in the protection and the management of the geopark area were identified. The lack of trained and qualified work force, sustainable financial resources, local participation, and education are the other major issues in terms of sustaining geotourismin Kızılcahamam - Çamlıdere Geopark. These deficiencies can be corrected under the UNESCO GGN (Global Geopark Network criteria.

  10. [Geisteswissenschaften und Publizistik im Baltikum des 19. und frühen 20. Jahrhunderts] / Gert von Pistohlkors

    Index Scriptorium Estoniae

    Pistohlkors, Gert von, 1935-


    Arvustus: Geisteswissenschaften und Publizistik im Baltikum des 19. und frühen 20. Jahrhunderts. Hrsg. von Norbert Angermann, Wilhelm Lenz und Konrad Maier. (Schriften der Baltischen Historischen Kommission, Bd. 17; Baltische Biographische Forschungen, Bd. 1.) Lit. Münster 2011

  11. Kommunikationsprobleme zwischen deutschen Expatriates und Chinesen in der wirtschaftlichen Zusammenarbeit -- Empirische Erfahrungen und Analyse der Einflußfaktoren


    Shi, Hongxia


    Die vorliegende Arbeit untersucht die empirischen Erfahrungen und die Einflußfaktoren der Kommunikationsprobleme der deutschen Expatriates und Chinesen in der wirtschaftlichen Zusammenarbeit. Die Untersuchung basiert auf einem Datenmaterial, das aus 86 Interviewgesprächen mit Betroffenen besteht. Zentrale Fragestellungen der vorliegenden Arbeit sind: 1. Mit welchen Kommunikationsproblemen werden die befragten deutschen Expatriates und Chinesen in ihrer interkulturellen Kommunikation miteinand...

  12. [Glanz und Elend - Mythos und Wirklichkeit der Herrenhäuser im Baltikum] / Karsten Brüggemann

    Index Scriptorium Estoniae

    Brüggemann, Karsten, 1965-


    Arvustus: Glanz und Elend - Mythos und Wirklichkeit der Herrenhäuser im Baltikum. Hrsg. von Ilse von zur Mühlen im Auftrag der Carl-Schirren-Gesellschaft e.V. und des Ostpreußischen Landesmuseums Lüneburg. Kunstverlag Josef Fink. Lindenberg im Allgäu 2012

  13. Wie schneiden Sie ab?: Studie über Kontroll- und Prüfungsaktivitäten bei mittelgrossen Unternehmen, Spitälern und Hochschulen in der Schweiz


    Ruud, T F; Isufi, S; Friebe, P; Stebler, W; Seheri, F; Emmenegger, M


    Kontroll- und Prüfungsaktivitäten unterstützen den Verwaltungsrat und die Geschäftsleitung bei der Steuerung und Kontrolle des Unternehmens. Bei mittelgrossen Unternehmen ist aufgrund der begrenzten personellen und finanziellen Ressourcen ein effektiver und effizienter Einsatz dieser Aktivitäten unerlässlich. Auch bei Spitälern und Hochschulen gewinnen Kontroll- und Prüfungsaktivitäten infolge erhöhter Wettbewerbsintensität und steigenden Kostendrucks sowie zunehmender Unabhängigkeit diese...

  14. Bewältigungsstrategien der Oberwalliser Primarlehrpersonen und Massnahmen der Gesundheitsförderung an Oberwalliser Primarschulen bei Stress und Burnout


    Imhof, Barbara; Mattig, Astrid


    Die vorliegende Studie befasst sich mit der Gesundheitsförderung bei Stress und Burnout an den Oberwalliser Primarschulen und der Bewältigungsstrategien der Oberwalliser Primarlehrpersonen bei Stress und Burnout. Der theoretische Teil befasst sich mit Stress und Burnout und der Bewältigung von Stress und Burnout. Verschiedene Aspekte des Lehrerberufs werden näher angeschaut und es werden mögliche Massnahmen der Gesundheitsförderung bei Stress und Burnout aufgeführt. Die Untersuchung zeigt, da...

  15. Soziologische Wissenskulturen zwischen individualisierter Inspiration und prozeduraler Legitimation. Zur Entwicklung qualitativer und interpretativer Sozialforschung in der deutschen und französischen Soziologie seit den 1960er Jahren

    Directory of Open Access Journals (Sweden)

    Reiner Keller


    Full Text Available Wie wissen Soziologinnen und Soziologen, was sie wissen? Trotz der Internationalisierung der Soziologie bestehen nach wie vor starke sprachräumliche Unterschiede in der soziologischen Wissensproduktion, in eingesetzten Theorien, Methoden und Fragestellungen. Der nachfolgende Beitrag erläutert die Entwicklung und Ausprägung der Unterschiedlichkeit soziologischer Wissenskulturen im Hinblick auf den Einsatz qualitativer bzw. interpretativer Ansätze seit den 1960er Jahren in Deutschland und Frankreich. Er stützt sich auf ein von uns 2012-2014 geleitetes Forschungsprojekt und dessen empirische Grundlagen: Dokumentenanalysen und Interviews. Wissenskulturen werden als die Arten und Weisen der Produktion und Legitimation von (hier: soziologischem Wissen verstanden. Diesbezüglich lässt sich von der Erkenntnisproduktion als dem zentralen Handlungsproblem soziologischen Forschens sprechen. Während für die französischsprachige Soziologie diagnostisch von einer Lösung dieses Erkenntnisproblems durch die den Forschenden zugeschriebenen Kompetenzen und Inspirationen ausgegangen werden kann, schiebt sich im deutschsprachigen Raume eine prozedurale Legitimation durch Verfahren in den Vordergrund. Der Beitrag rekonstruiert exemplarisch die Ausgangssituation dieser Entwicklungen um die Wende zu den 1960er Jahren und bettet sie in die weitere Entfaltung der jeweiligen Soziologien ein. Er will damit zur gegenwärtigen Entwicklung einer reflexiven Soziologie beitragen. URN:

  16. "Tabula Sinvs Venetici" von W. Barents und ihre Geschichtilische und Geographische Bedeutung

    Directory of Open Access Journals (Sweden)

    Mithad Kozličić


    Full Text Available In der wissenschaftlichen Literatur sind zwei Varianten der Seekarte der Adria vom niederländischen Seefahrer und Polarforscher Willem Barents (1550-1597 bekannt. Die erste, in diesem Aufsatz als K-1 bezeichnete Karte, wurde in Amsterdam 1595 hergestellt und gedruckt. Sie hatte anfänglich eine praktisch-navigatorische Funktion. Die zweite, K-2, ins Jahr 1595 datierte (1637-1662 Karte, wurde als geostrategische Karte der Adria und der südlichen Teile Europas ausgenützt. An den adriatischen Nordküsten, besonders in ihrem Hinterland, geschahen mit dem Durchbruch der Türken seit der Hälfte des 16. Jahrhunderts wichtige militärische und politische Änderungen. In den “Atlanten” des Niederländers Jan (Johann; Joannes Janssonius (1588-1664 fehlte gerade solch eine Karte, die auch mehrmals in Amsterdam gedruckt wurde, aber zwischen 1637 und 1662. Die K-1 von Barents, deren Druckplatte Janssonius zur Verfügung hatte, konnte diese Funktion befriedigen. Deswegen machte Janssonius nur die nötigen dem darstellenden Standard der ersten Hälfte des 17. Jahrhunderts entsprechenden Änderungen, und als solche wurde sie gedruckt. Die K-2 verlor ihre ursprüngliche praktisch-navigatorische Funktion und wurde eine Karte von geostrategischer Bedeutung. Mit diesen Grundfragen befaßt sich dieser Aufsatz.

  17. [Vilis Kolms. Das Rigaer Gesangbuch und die kirchenordnung von 1530]/ Dennis Hortmuth

    Index Scriptorium Estoniae

    Hormuth, Dennis


    Arvustus: .Vilis Kolms. Das Rigaer Gesangbuch und die kirchenordnung von 1530. In: Die baltischen Lande im Zeitalter der Reformation und Konfessionaliesierung. Livland, Estland, Ösel, Ingermanland, Kurland und Lettgallen. Stadt, Land und Konfession 1500-1721. Teil 2 (=Katholisches Leben und Kirchenreform im Zeitalter der Glaubensspaltung 70). Münster, 2010. S. 175-190

  18. Diffuser Haarausfall und klinische Endokrinologie: Neue Erkenntnisse

    Directory of Open Access Journals (Sweden)

    Liptak J


    Full Text Available Diffuser Haarausfall ist ein häufiges Krankheitsbild in der täglichen Praxis, dessen Diagnostik allerdings oft eine Herausforderung darstellt. In den vergangenen 10 Jahren wurden große Fortschritte in der Erforschung der Effekte diverser Hormone erzielt. In murinen Haarfollikeln wird Corticoliberin (Corticotropin-releasing Hormone [CRH] mit einem Peak in der Anagenphase (Wachstumsphase exprimiert. Ein stressinduziert erhöhter CRH-Spiegel kann durch Aktivierung von Mastzellen zu erhöhtem Haarverlust führen. Melatonin wird ebenfalls im Haarfollikel exprimiert und wirkt dort auf unterschiedliche Rezeptoren. Besonders der nukleäre Retinoic Acid Receptor-(RAR- Related Orphan-Receptor alpha (RORα scheint regulatorisch auf haarzyklusabhängige Prozesse zu wirken und wird auch abhängig vom Haarzyklus exprimiert. Melatonin greift zudem in androgen- und östrogenvermittelte Signaltransduktionswege ein. Eine topische Anwendung von Melatonin kann zu einer Zunahme der Anagenhaare führen. Auch Leptin wird im Haarfollikel exprimiert und beeinflusst Haarwachstum und Hautregeneration durch Aktivierung von STAT3. Bei Mäusen konnte durch Leptin die Anagenphase induziert werden. Über den Zusammenhang zwischen androgenetischer Alopezie und Metabolischem Syndrom wurden zahlreiche widersprüchliche Daten veröffentlicht. Zuletzt wies eine große koreanische Studie eine positive Assoziation der Krankheitsbilder bei Frauen nach, jedoch nicht bei Männern. Prolaktin induziert den verfrühten Übergang zur Katagenphase, senkt die Proliferationsrate der Keratinozyten im Haarfollikel und steigert deren Apoptoserate. Eine zu Haarausfall führende Hyperprolaktinämie kann unter anderem durch diverse Medikamente, insbesondere typische und atypische Neuroleptika, hervorgerufen werden. Zahlreiche Studien an Mäusen konnten belegen, dass der Vitamin-D-Rezeptor (VDR eng mit dem Haarwachstum assoziiert ist. Dieser scheint den Haarzyklus unabhängig von seinen Liganden

  19. Big Data in kleinen und mittleren Unternehmen: Eine empirische Bestandsaufnahme


    Vossen, Gottfried; Lechtenbörger, Jens; Fekete, David


    Dieser Bericht untersucht das Potential von Big Data in und für kleine und mittlere Unternehmen (KMU). Dafür werden mittels einer Umfrage, Fokus-Interviews und zusätzlichen Recherchen die Potentiale und Herausforderungen bei Big Data untersucht, welche für KMU zu Tragen kommen. Der Begriff Big Data selbst wird genauer betrachtet und es wird erklärt, welche Dimensionen abseits schierer Größe ebenfalls dazu zählen, wie etwa Vielfalt oder Schnelligkeit der Daten. Weiter wird mit eingängigen Prax...

  20. Von Nischen und Infrastrukturen - Herausforderungen und neue Ansätze politischer Technologien

    Directory of Open Access Journals (Sweden)

    Felix Stalder


    Full Text Available Neue Technologien aus dem aktivistischen Umfeld bieten radikale Alternativen zu kultureller Nischenbildung und zentralisierten Web 2.0-Infrastrukturen. Die sozialen und politischen Realitäten der Digitalisierung und Vernetzung sind heute von zwei konstitutiven, aber grundsätzlich unterschiedlichen, ja teilweise sogar entgegengesetzten Dynamiken geprägt. Beide stellen den Medienaktivismus vor neue Herausforderungen. Zum einen können wir ein Aufblühen neuer kultureller Nischen und horizontaler Organisationsformen beobachten. Zum anderen erleben wir gleichzeitig eine enorme Zentralisierung und Konzentration auf der Ebene der Plattformen, welche einen grossen Teil der infrastrukturellen Grundlage des Wachstum der Nischen und neuen Kooperationsmuster darstellen. Nachdem der Aufbau alternativer Infrastrukturen – Zeitschriften, TV Kanäle und Internetplattformen – in den ersten 30 Jahren medienaktivistischer Projekte eine grosse Rolle gespielt hat (Stalder 2008 sind diese Fragen in den letzten 10 Jahren etwas in den Hintergrund getreten. Denn die Komplexität der Infrastrukturen nahm stetig zu, was es immer aufwendiger machte, sie zu betreiben und die neuen, offene Plattformen, wie sie für Web 2.0 typisch sind, stellten allen - scheinbar ohne Einschränkungen - mächtige Werkzeuge zu Verfügung. Warum eine eigene Plattform betreiben, wenn grosse professionelle Anbieter das besser, sicherer und kostenfrei anbieten? Heute sind die Probleme dieser Entwicklungen aber deutlich zu erkennen. Im Folgenden werden die Herausforderungen dieser Nischenbildung, die dunkle Seite der zentralisierten Infrastrukturen sowie die darauf reagierenden, neue Entwürfe für de-zentrale Infrastrukturen skizziert.