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  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)

    2008-06-15

    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.

    Science.gov (United States)

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

    2017-09-01

    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.

    Science.gov (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

    2015-05-14

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

    DEFF Research Database (Denmark)

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

    2011-01-01

    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...... the MDS/AML classification system, incorporating as yet unknown molecular genetic and epigenetic pathomechanisms, which are likely reflected by aberrant gene expression patterns. In this study, we provide a comprehensive review on how GEP has contributed to a refined molecular taxonomy of MDS and AML...... technologies, which will continue to improve our understanding of malignant transformation in myeloid malignancies and thereby contribute to individualized risk-adapted treatment strategies for MDS and AML patients....

  5. Age-related epigenetic drift in the pathogenesis of MDS and AML.

    Science.gov (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

    2014-04-01

    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.

  6. [Application of Next Generation Sequencing for AML/MDS Diagnosis and Treatment].

    Science.gov (United States)

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

    2017-12-01

    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.

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

    International Nuclear Information System (INIS)

    Yanada, Masamitsu

    2008-01-01

    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.)

  8. The emerging role of immune checkpoint based approaches in AML and MDS.

    Science.gov (United States)

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

    2018-04-01

    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.

  9. Focal Adhesion Kinase as a Potential Target in AML and MDS.

    Science.gov (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

    2017-06-01

    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.

  10. Study of Rpl22 in MDS and AML

    Science.gov (United States)

    2015-10-01

    depleting cells expressing lineage markers (Fig.4). We also analyzed the phenotype in Rpl22-/-p53-/- mice and found the mice exhibit similar phenotype...prognostic marker in AML. On the other hand, because we found Like1 is induced upon Rpl22 inactivation and its expression is required and sufficient...Ferreira AM, et al. (2014) High frequency of RPL22 mutations in microsatellite -unstable colorectal and endometrial tumors. Hum Mutat 35(12):1442-1445. 9

  11. Connect MDS/AML: design of the myelodysplastic syndromes and acute myeloid leukemia disease registry, a prospective observational cohort study.

    Science.gov (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

    2016-08-19

    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

  12. [Combination of busulfan with increased-dose of fludarabine as conditioning regimen for MDS and MDS-AML patients with allo-HSCT].

    Science.gov (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

    2015-06-01

    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.

  13. Therapy Related AML/MDS Following Treatment for Childhood Cancer: Experience from a Tertiary Care Centre in North India.

    Science.gov (United States)

    Vyas, Chintan; Jain, Sandeep; Kapoor, Gauri

    2018-01-01

    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.

  14. 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.

    2016-01-01

    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

  15. WT1 vaccination in AML and MDS: A pilot trial with synthetic analog peptides.

    Science.gov (United States)

    Brayer, Jason; Lancet, Jeffrey E; Powers, John; List, Alan; Balducci, Lodovico; Komrokji, Rami; Pinilla-Ibarz, Javier

    2015-07-01

    Peptide vaccines are capable of eliciting immune responses targeting tumor-associated antigens such as the Wilms' Tumor 1 (WT1) antigen, often overexpressed in myeloid malignancies. Here, we assessed the safety, tolerability, and immunogenicity of a polyvalent WT1 peptide vaccine. Individuals with WT1-positive acute myeloid leukemia (AML) in first (CR1) or second (CR2) remission or with higher-risk myelodysplastic syndrome (MDS) following at least 1 prior line of therapy were vaccinated with a mixture of peptides derived from the WT1 protein, with sargramostim injections before vaccination to amplify immunogenicity. Six vaccinations were delivered biweekly, continuing then monthly until patients received 12 vaccinations or showed disease relapse or progression. Therapeutic efficacy was evaluated by progression-free and overall survival. Immune responses were evaluated by delayed-type hypersensitivity testing and T-cell IFNγ ELISPOT at specified intervals. In 16 patients who received at least one vaccination, 10 completed the planned course of six vaccinations and six continued for up to six additional monthly vaccinations. Vaccinations were well tolerated, with no patients discontinuing due to toxicity. One of two patients with high-risk MDS experienced a prolonged decrease in transfusion dependence. Two of 14 AML patients demonstrated relapse-free survival >1 year. Both patients were in CR2 at time of vaccination, with duration of their remission exceeding duration of their first remission, suggesting a potential benefit. Our WT1 vaccine was well-tolerated. The clinical benefit that we observed in several patients suggests engagement of a protective immune response, indicating a need for further trials. © 2015 Wiley Periodicals, Inc.

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

    Directory of Open Access Journals (Sweden)

    Udit Bhaskar Bhatnagar

    2016-01-01

    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.

  17. Phase I dose escalation study of bortezomib in combination with lenalidomide in patients with myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML).

    Science.gov (United States)

    Attar, Eyal C; Amrein, Philip C; Fraser, James W; Fathi, Amir T; McAfee, Steven; Wadleigh, Martha; Deangelo, Daniel J; Steensma, David P; Stone, Richard M; Foster, Julia; Neuberg, Donna; Ballen, Karen K

    2013-09-01

    We conducted a phase I dose escalation study to determine the maximal tolerated dose of bortezomib that could be combined with standard dose lenalidomide in patients with MDS or AML. Treatment consisted of bortezomib (IV) on Days 1, 4, 8, and 11 and lenalidomide 10mg daily (PO) days 1-21 in 28 day cycles for up to 9 cycles. 23 patients (14 MDS/CMML, 9 AML) were enrolled. The maximally tested dose of bortezomib, 1.3mg/m(2), was tolerable in this regimen. Responses were seen in patients with MDS and AML. Further testing of this regimen is planned. Copyright © 2013 Elsevier Ltd. All rights reserved.

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

    Science.gov (United States)

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

    2017-07-01

    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.

  19. Similar Transplant Outcomes for AML/MDS Patients with Haploidentical versus 10/10 HLA Matched Unrelated and Related Donors

    Science.gov (United States)

    Di Stasi, Antonio; Milton, Denái R.; Poon, LM; Hamdi, Amir; Rondon, Gabriela; Chen, Julianne; Pingali, Sai R.; Konopleva, Marina; Kongtim, Piyanuch; Alousi, Amin; Qazilbash, Muzaffar H.; Ahmed, Sairah; Bashir, Qaiser; Al-atrash, Gheath; Oran, Betul; Hosing, Chitra M.; Kebriaei, Partow; Popat, Uday; Shpall, Elizabeth J.; Lee, Dean A.; de Lima, Marcos; Rezvani, Katayoun; Khouri, Issa F.; Champlin, Richard E.; Ciurea, Stefan O.

    2015-01-01

    Allogeneic stem-cell transplantation for patients with acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) has been performed primarily with an HLA matched donor. Outcomes of haploidentical transplantation have recently improved, and a comparison between these donor sources in a uniform cohort of patients has not been performed. We evaluated outcomes of 227 patients with AML/MDS treated with melphalan-based conditioning. Donors were matched related (MRD) (N=87, 38%), matched unrelated (MUD) (N=108, 48%), or haploidentical (N=32, 14%). No significant differences were found between haploidentical and MUD transplant outcomes; however, there was a trend for improved outcomes in the MRD group with a 3-year progression-free survival for patients in remission of 57%, 45% and 41% for MRD, MUD and haploidentical, respectively (P=0.417). Recovery of T-cell subsets was similar for all groups. These results suggest that haploidentical donors can safely extend transplantation for AML/MDS patients without an HLA matched donor. Prospective studies comparing haploidentical and MUD transplants are warranted. PMID:25263628

  20. Impact of Cytogenetics on Outcome of De novo and Therapy-related AML and MDS after Allogeneic Transplantation

    Science.gov (United States)

    Armand, Philippe; Kim, Haesook T.; DeAngelo, Daniel J.; Ho, Vincent T.; Cutler, Corey S.; Stone, Richard M.; Ritz, Jerome; Alyea, Edwin P.; Antin, Joseph H.; Soiffer, Robert J.

    2009-01-01

    Cytogenetics has an important impact on the prognosis of patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT) for AML or MDS. However, it is unclear whether currently accepted cytogenetic risk groups, which were established for patients treated mostly with standard therapy, are optimally discriminating for patients undergoing HSCT. Also, the impact of cytogenetics in the growing population of patients with therapy-related disease has not been completely elucidated. In this study, we retrospectively analyzed data on 556 patients with AML or MDS transplanted at our institution. We examined, in multivariate analyses, the contribution of cytogenetics to survival, relapse, and non-relapse mortality (NRM) for the 476 patients with de novo disease. We used these results to establish an optimal cytogenetic grouping scheme. We then applied this grouping scheme to the 80 patients with therapy-related disease. Our proposed three-group cytogenetic classification outperformed the established grouping schemes for both de novo and therapy-related disease. When classified by this new scheme, cytogenetics was the strongest prognostic factor for overall survival in our cohort, through its impact on the risk of relapse (and not on NRM). After accounting for cytogenetics, patients with therapy-related AML or MDS had an equivalent outcome to those with de novo disease. This study demonstrates the impact of cytogenetics on the risk of relapse and death for patients with both de novo and therapy-related disease undergoing transplantation; it also emphasizes the necessity of using cytogenetics to stratify patients entering clinical trials, and provides a system for doing so, which can be validated in a multi-institutional database. PMID:17531775

  1. 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

    2013-01-01

    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...

  2. Fludarabine with pharmacokinetically-guided IV busulfan is superior to fixed-dose delivery in pretransplant conditioning of AML/MDS patients

    Science.gov (United States)

    Andersson, Borje S.; Thall, Peter F.; Valdez, Benigno C.; Milton, Denái R.; Al-Atrash, Gheath; Chen, Julianne; Gulbis, Alison; Chu, Diem; Martinez, Charles; Parmar, Simrit; Popat, Uday; Nieto, Yago; Kebriaei, Partow; Alousi, Amin; de Lima, Marcos; Rondon, Gabriela; Meng, Qing H.; Myers, Alan; Kawedia, Jitesh; Worth, Laura L.; Fernandez-Vina, Marcelo; Madden, Timothy; Shpall, Elizabeth J.; Jones, Roy B.; Champlin, Richard E.

    2016-01-01

    We hypothesized that IV Busulfan (Bu) dosing could be safely intensified through pharmacokinetic (PK-) dose guidance to minimize the inter-patient variability in systemic exposure (SE) associated with body-sized dosing, and this should improve outcome of AML/MDS patients undergoing allogeneic stem cell transplantation (allo-HSCT). To test this hypothesis, we treated 218 patients (median age 50.7 years, male/female 50/50%) with fludarabine (Flu) 40 mg/m2 once daily ×4, each dose followed by IV Bu, randomized to 130 mg/m2 (N=107) or PK-guided to average daily SE, AUC of 6,000 µM-min (N=111), stratified for remission-status, and allo-grafting from HLA-matched donors. Toxicity and graft vs. host disease (GvHD) rates in the groups were similar; the risk of relapse or treatment-related mortality remained higher in the fixed-dose group throughout the 80-month observation period. Further, PK-guidance yielded safer disease-control, leading to improved overall and progression-free survival, most prominently in MDS-patients and in AML-patients not in remission at allo-HSCT. We conclude that AML/MDS patients receiving pretransplant conditioning treatment with our 4-day regimen may benefit significantly from PK-guided Bu-dosing. This could be considered an alternative to fixed dose delivery since it provides the benefit of precise dose delivery to a predetermined SE without increasing risk(s) of serious toxicity and/or GvHD. PMID:27991894

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

    DEFF Research Database (Denmark)

    Ørskov, A. D.; Treppendahl, M. B.; Skovbo, A.

    2015-01-01

    The hypomethylating agents (HMAs) are standard therapy for patients with higher-risk myelodysplastic syndrome (MDS); however, the majority of the patients will lose their response to HMAs over time due to unknown mechanisms. It has recently been shown that T cell expression of the immunoinhibitory......-responding patients compared to healthy controls (p = 0.023). Accordingly, in addition to their beneficial function, HMAs induce PD-1 expression on T cells in the MDS microenvironment, thereby likely hampering the immune response against the MDS blasts. Thus, we suggest that activation of the PD-1 checkpoint during...

  4. Platelet doubling after the first azacitidine cycle is a promising predictor for response in myelodysplastic syndromes (MDS), chronic myelomonocytic leukaemia (CMML) and acute myeloid leukaemia (AML) patients in the Dutch azacitidine compassionate named patient programme

    NARCIS (Netherlands)

    van der Helm, Lieke H.; Alhan, Canan; Wijermans, Pierre W.; van Marwijk Kooy, Marinus; Schaafsma, Ron; Biemond, Bart J.; Beeker, Aart; Hoogendoorn, Mels; van Rees, Bastiaan P.; de Weerdt, Okke; Wegman, Jurgen; Libourel, Ward J.; Luykx-de Bakker, Sylvia A.; Minnema, Monique C.; Brouwer, Rolf E.; Croon-de Boer, Fransien; Eefting, Matthijs; Jie, Kon-Siong G.; van de Loosdrecht, Arjan A.; Koedam, Jan; Veeger, Nic J. G. M.; Vellenga, Edo; Huls, Gerwin

    2011-01-01

    The efficacy of azacitidine in the treatment of high-risk myelodysplastic syndromes (MDS), chronic myelomonocytic leukaemia (CMML) and acute myeloid leukaemia (AML) (20-30% blasts) has been demonstrated. To investigate the efficacy of azacitidine in daily clinical practice and to identify predictors

  5. IS THE AMPLIFICATION OF c-MYC, MLL AND RUNX1 GENES IN AML AND MDS PATIENTS WITH TRISOMY 8, 11 AND 21 A FACTOR FOR A CLONAL EVOLUTION IN THEIR KARYOTYPE?

    Science.gov (United States)

    Angelova, S; Spassov, B; Nikolova, V; Christov, I; Tzvetkov, N; Simeonova, M

    2015-01-01

    The aim of our study was 1) to define if the amplification of c-MYC, MLL and RUNX1 genes is related to the progressive changes of the karyotype in patients with AML and MDS with trisomy 8, 11 and 21 (+8, +11 and +21) in bone marrow and 2) can that amplification be accepted as part of the clonal evolution (CE). Karyotype analysis was performed in 179 patients with AML or MDS with the different chromosomal aberrations (CA) aged 16-81. The findings were distributed as follow: initiating balanced CA (n = 60), aneuploidia (n = 55), unbalanced CA (n = 64). Amplification of c-MYC, MLL and RUNX1 genes by means of fluorescence in situ hybridization (FISH) was found in 35% (7 out of 20) of AML and MDS patients with +8, +11 u +21 as single CA in their karyotype; in 63.6% of pts (7 out of 11)--with additional numerical or structural CA and in 75% (9 out of 12)--with complex karyotype. We assume that the amplification of the respective chromosomal regions in patients with +8, +11 and +21 is related to CE. Considering the amplification as a factor of CE, we established 3 patterns of karyotype development depending on the type of the initiating CA in it. Significant statistical differences were found between the three patterns regarding the karyotype distribution in the different stages of progression (p < 0.001).

  6. Childhood MDS

    Science.gov (United States)

    ... Myeloma Awareness Month Help Us Find a Cure Childhood MDS Childhood MDS Print Glossary To access information about coping ... be the same treatment approach for the disorder. Childhood MDS Subtypes Subtypes of primary childhood MDS are ...

  7. A phase 1b/2b multicenter study of oral panobinostat plus azacitidine in adults with MDS, CMML or AML with ⩽30% blasts.

    Science.gov (United States)

    Garcia-Manero, G; Sekeres, M A; Egyed, M; Breccia, M; Graux, C; Cavenagh, J D; Salman, H; Illes, A; Fenaux, P; DeAngelo, D J; Stauder, R; Yee, K; Zhu, N; Lee, J-H; Valcarcel, D; MacWhannell, A; Borbenyi, Z; Gazi, L; Acharyya, S; Ide, S; Marker, M; Ottmann, O G

    2017-12-01

    Treatment with azacitidine (AZA), a demethylating agent, prolonged overall survival (OS) vs conventional care in patients with higher-risk myelodysplastic syndromes (MDS). As median survival with monotherapy is <2 years, novel agents are needed to improve outcomes. This phase 1b/2b trial (n=113) was designed to determine the maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D) of panobinostat (PAN)+AZA (phase 1b) and evaluate the early efficacy and safety of PAN+AZA vs AZA monotherapy (phase 2b) in patients with higher-risk MDS, chronic myelomonocytic leukemia or oligoblastic acute myeloid leukemia with <30% blasts. The MTD was not reached; the RP2D was PAN 30 mg plus AZA 75 mg/m 2 . More patients receiving PAN+AZA achieved a composite complete response ([CR)+morphologic CR with incomplete blood count+bone marrow CR (27.5% (95% CI, 14.6-43.9%)) vs AZA (14.3% (5.4-28.5%)). However, no significant difference was observed in the 1-year OS rate (PAN+AZA, 60% (50-80%); AZA, 70% (50-80%)) or time to progression (PAN+AZA, 70% (40-90%); AZA, 70% (40-80%)). More grade 3/4 adverse events (97.4 vs 81.0%) and on-treatment deaths (13.2 vs 4.8%) occurred with PAN+AZA. Further dose or schedule optimization may improve the risk/benefit profile of this regimen.

  8. Pathophysiology of MDS: genomic aberrations.

    Science.gov (United States)

    Ichikawa, Motoshi

    2016-01-01

    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.

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

    DEFF Research Database (Denmark)

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

    2015-01-01

    population-based paediatric acute myeloid leukaemia (AML) cohort. We included children diagnosed with de novo AML, 0-18 years of age from the Nordic countries and Hong Kong from 1993 to 2012. Data were retrieved from the Nordic Society for Paediatric Haematology and Oncology AML database and patients......) (44%). In conclusion, the WHO classification allocated 15% to AML-MDS, 44% to NOS and grouped together entities with clearly different outcome, therefore limiting the applicability of the current WHO classification in children with AML....

  10. 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

    2016-01-01

    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.

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

    Science.gov (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

    2016-01-27

    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.

  12. 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

    2010-01-01

    by treatment with chemotherapy and/or irradiation (t-AML). Cytogenetic analysis was carried out in 93%, of which 61% had clonal chromosome aberrations. MDS-AML correlated to a normal karyotype (P ... novo AML patients diagnosed in the same area and period. In this comparison, s-AML only correlated to -7 (P = 0.02). In 42 patients, we found that MDS patients with an abnormal karyotype were more likely to show cytogenetic evolution during progression to AML than MDS patients with a normal karyotype...... (P = 0.01). We conclude that population-based cytogenetic studies of adult s-AML and age- and sex-matched de novo AML show comparable distributions of chromosome abnormalities....

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

    OpenAIRE

    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

    2008-01-01

    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...

  14. Genetic predisposition syndromes: when should they be considered in the work-up of MDS?

    Science.gov (United States)

    Babushok, Daria V; Bessler, Monica

    2015-03-01

    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.

  15. Implication of microRNAs in the Pathogenesis of MDS

    Science.gov (United States)

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

    2016-01-01

    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

  16. Myelodysplastic changes mimicking MDS following treatment for osteosarcoma

    DEFF Research Database (Denmark)

    Løhmann, Ditte

    Myelodysplastic changes mimicking MDS following treatment for osteosarcoma Ditte Juel Adolfsen Løhmann, Department of Pediatrics, Aarhus University Hospital, Skejby, Denmark Authors: Ditte Juel Adolfsen Løhmann and Henrik Hasle. Therapy-related myelodysplastic syndrome/acute myeloid leukaemia (t-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...... MDS (refractory anaemia with excess blasts) with monosomy 7 was found and a hematopoietic stem cell transplant was performed. In the other case MDS without excess of blasts was found and a spontaneous normalization of the biochemistry occurred. In conclusion in our study most patients treated...

  17. Acute myeloid leukemia (AML with erythroid predominance exhibits clinical and molecular characteristics that differ from other types of AML.

    Directory of Open Access Journals (Sweden)

    Zhuang Zuo

    Full Text Available The clinical importance of erythroid predominance in bone marrow of patients with acute myeloid leukemia (AML is controversial. These cases represent a heterogeneous group of diseases that historically have been classified into different categories. We studied 313 AML patients and specifically compared the clinical, cytogenetic, and molecular features of cases of AML with erythroid predominance, arbitrarily defined as ≥50% erythroid precursors, to AML cases without erythroid predominance. We also assessed 51 patients with a high-grade myelodysplastic syndrome (MDS, refractory anemia with excess blasts (RAEB. All neoplasms were classified according to the World Health Organization classification. With the exception of therapy-related AML/MDS, the presence of erythroid predominance in variously classified categories of AML was associated with a survival advantage. In addition, AML with erythroid predominance had a lower frequency of cytogenetic abnormalities as well as a lower frequency of mutations involving NPM1, NRAS and FLT3 as compared with AML without erythroid predominance. We conclude that the clinical, cytogenetic, and molecular features of AML with erythroid predominance in the non-therapy-related setting are much closer to those of a high-grade myelodysplastic syndrome than they are to other types of AML.

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

    Science.gov (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

    2017-09-26

    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.

  19. TREATMENT OF LOW-BLAST COUNT AML USING HYPOMETHYLATING AGENTS

    Directory of Open Access Journals (Sweden)

    Eleonora De Bellis

    2017-07-01

    Full Text Available In 2002, the WHO classification reduced the proportion of blasts in the bone marrow (BM necessary for the diagnosis of acute myeloid leukemia (AML from 30% to 20%, eliminating the RAEB-t subtype of myelodysplastic syndromes (MDS. However, this AML subtype, defined as low-blast count AML (LBC-AML, with 20-30% BM-blasts is characterized by peculiar features, as increased frequency in elderly individuals and after cytotoxic treatment for a different primary disease (therapy-related, poor-risk cytogenetics, lower white blood cell counts, and less frequent mutations of NPM1 and FLT3 genes. The clinical course of this entity is often similar to MDS with 10-19% BM-blasts. The hypomethylating agents azacitidine and decitabine have been shown to induce responses and prolong survival both in MDS and LBC-AML.  The role of these agents has been also demonstrated in AML with >30% BM-blasts, particularly in patients with poor-risk cytogenetics and in AML with myelodysplasia related changes. Most recent studies are evaluating strategies to improve outcome, including combinations of hypomethylating agents with immune-response checkpoint inhibitors, which have a role in cancer immune surveillance. Efforts are also ongoing to identify mutations which may predict response and survival in these patients.

  20. Atmospheric Measurements Laboratory (AML)

    Data.gov (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...

  1. Inhibition of WNT signaling in the bone marrow niche prevents the development of MDS in the Apcdel/+ MDS mouse model.

    Science.gov (United States)

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

    2017-06-01

    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.

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

    Science.gov (United States)

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

    2017-06-01

    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.

  3. Increased separase activity and occurrence of centrosome aberrations concur with transformation of MDS.

    Science.gov (United States)

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

    2018-01-01

    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

  4. MDS: Recent progress in molecular pathogenesis and clinical aspects.

    Science.gov (United States)

    Harada, Hironori

    2017-01-01

    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.

  5. Study of RpI22 in MDS and AML

    Science.gov (United States)

    2016-12-01

    1203. 8. Ferreira AM, et al. (2014) High frequency of RPL22 mutations in microsatellite -unstable colorectal and endometrial tumors. Hum Mutat 35(12... bearing RPL22 mutations, the expres- sion of both KLF2 and S1PR1 was reduced (Fig. 6D; Supplemen- tary Fig. S4). Furthermore, knockdown of Rpl22 in human...4. Zhang Y, Duc AC, Rao S, Sun XL, Bilbee AN, Rhodes M, et al. Control of hematopoietic stem cell emergence by antagonistic functions of ribosomal

  6. MDS MIC Catalog Inputs

    Science.gov (United States)

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

    2006-01-01

    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.

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

    Science.gov (United States)

    Bellos, Frauke; Kern, Wolfgang

    2014-09-25

    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.

  8. Access/AML -

    Data.gov (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...

  9. Aplastic Anemia & MDS International Foundation

    Science.gov (United States)

    ... In Treatment at NIH "The Aplastic Anemia and MDS International Foundation is helping patients like me cope with bone marrow failure disease." Diseases Aplastic Anemia Myelodysplastic Syndromes (MDS) Paroxysmal Nocturnal Hemoglobinuria (PNH) Related Diseases Treatments ...

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

    Science.gov (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

    2018-01-01

    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.

  11. The NAE inhibitor pevonedistat interacts with the HDAC inhibitor belinostat to target AML cells by disrupting the DDR.

    Science.gov (United States)

    Zhou, Liang; Chen, Shuang; Zhang, Yu; Kmieciak, Maciej; Leng, Yun; Li, Lihong; Lin, Hui; Rizzo, Kathryn A; Dumur, Catherine I; Ferreira-Gonzalez, Andrea; Rahmani, Mohamed; Povirk, Lawrence; Chalasani, Sri; Berger, Allison J; Dai, Yun; Grant, Steven

    2016-05-05

    Two classes of novel agents, NEDD8-activating enzyme (NAE) and histone deacetylase (HDAC) inhibitors, have shown single-agent activity in acute myelogenous leukemia (AML)/myelodysplastic syndrome (MDS). Here we examined mechanisms underlying interactions between the NAE inhibitor pevonedistat (MLN4924) and the approved HDAC inhibitor belinostat in AML/MDS cells. MLN4924/belinostat coadministration synergistically induced AML cell apoptosis with or without p53 deficiency or FLT3-internal tandem duplication (ITD), whereas p53 short hairpin RNA (shRNA) knockdown or enforced FLT3-ITD expression significantly sensitized cells to the regimen. MLN4924 blocked belinostat-induced antiapoptotic gene expression through nuclear factor-κB inactivation. Each agent upregulated Bim, and Bim knockdown significantly attenuated apoptosis. Microarrays revealed distinct DNA damage response (DDR) genetic profiles between individual vs combined MLN4924/belinostat exposure. Whereas belinostat abrogated the MLN4924-activated intra-S checkpoint through Chk1 and Wee1 inhibition/downregulation, cotreatment downregulated multiple homologous recombination and nonhomologous end-joining repair proteins, triggering robust double-stranded breaks, chromatin pulverization, and apoptosis. Consistently, Chk1 or Wee1 shRNA knockdown significantly sensitized AML cells to MLN4924. MLN4924/belinostat displayed activity against primary AML or MDS cells, including those carrying next-generation sequencing-defined poor-prognostic cancer hotspot mutations, and CD34(+)/CD38(-)/CD123(+) populations, but not normal CD34(+) progenitors. Finally, combined treatment markedly reduced tumor burden and significantly prolonged animal survival (P DDR in AML/MDS cells. This strategy warrants further consideration in AML/MDS, particularly in disease with unfavorable genetic aberrations. © 2016 by The American Society of Hematology.

  12. 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

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

    Directory of Open Access Journals (Sweden)

    Myrna Candelaria-Hernández

    2017-06-01

    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

  14. MDS 3.0 Frequency Report

    Data.gov (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...

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

    OpenAIRE

    Tong, Hongxi; Wang, Xiaoqing

    2016-01-01

    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...

  16. AML (Logistics Center) Local Area Network -

    Data.gov (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...

  17. Acute myeloid leukemia (AML) - children

    Science.gov (United States)

    Having a child with cancer can make you feel very alone. In a cancer support group, you can find people who are going ... Updated July 28, 2016. National Cancer Institute. www.cancer.gov/types/leukemia/patient/child-aml-treatment-pdq . Accessed August 3, 2016. Wei ...

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

    Science.gov (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

    2017-07-01

    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.

  19. Pediatric MDS: GATA screen the germline.

    Science.gov (United States)

    Stieglitz, Elliot; Loh, Mignon L

    2016-03-17

    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.

  20. Survey of expert opinions and related recommendations regarding bridging therapy using hypomethylating agents followed by allogeneic transplantation for high-risk MDS.

    Science.gov (United States)

    Sohn, Sang Kyun; Moon, Joon Ho

    2015-08-01

    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.

  1. Long Term Care Minimum Data Set (MDS)

    Data.gov (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...

  2. Hypotéza o MDS kódech

    OpenAIRE

    Kesely, Michal

    2010-01-01

    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...

  3. Patients with Fanconi anemia and AML have different cytogenetic clones than de novo cases of AML.

    Science.gov (United States)

    Rochowski, Andrzej; Olson, Susan B; Alonzo, Todd A; Gerbing, Robert B; Lange, Beverly J; Alter, Blanche P

    2012-11-01

    Specific cytogenetic clones might distinguish patients with unrecognized Fanconi anemia (FA) who present with acute myeloid leukemia (AML) from those with sporadic AML. Cytogenetic reports in literature cases of FA and AML were compared with de novo cases enrolled on CCG-2961. Gain of 1q, gain of 3q, monosomy 7, deleted 7q, gain of 13q, and deleted 20q were more frequent in FA AML; t(8;21), trisomy 8, t(9;11), t(6;9), and inversion 16 were exclusive to de novo AML cases. Observation of the FA AML cytogenetic clonal patterns should raise suspicion of an underlying leukemia predisposition syndrome and influence management. Copyright © 2012 Wiley Periodicals, Inc. This article is a U.S. Government work and is in the public domain in the USA.

  4. AML Guide: Information for Patients and Caregivers

    Science.gov (United States)

    ... personal exposure is from cigarette smoke. The average smoker is exposed to about 10 times the daily ... count) to count the numbers of red cells, white cells and platelets. Usually, patients with AML have ...

  5. Pediatric AML: From Biology to Clinical Management

    Directory of Open Access Journals (Sweden)

    Jasmijn D. E. de Rooij

    2015-01-01

    Full Text Available Pediatric acute myeloid leukemia (AML represents 15%–20% of all pediatric acute leukemias. Survival rates have increased over the past few decades to ~70%, due to improved supportive care, optimized risk stratification and intensified chemotherapy. In most children, AML presents as a de novo entity, but in a minority, it is a secondary malignancy. The diagnostic classification of pediatric AML includes a combination of morphology, cytochemistry, immunophenotyping and molecular genetics. Outcome is mainly dependent on the initial response to treatment and molecular and cytogenetic aberrations. Treatment consists of a combination of intensive anthracycline- and cytarabine-containing chemotherapy and stem cell transplantation in selected genetic high-risk cases or slow responders. In general, ~30% of all pediatric AML patients will suffer from relapse, whereas 5%–10% of the patients will die due to disease complications or the side-effects of the treatment. Targeted therapy may enhance anti-leukemic efficacy and minimize treatment-related morbidity and mortality, but requires detailed knowledge of the genetic abnormalities and aberrant pathways involved in leukemogenesis. These efforts towards future personalized therapy in a rare disease, such as pediatric AML, require intensive international collaboration in order to enhance the survival rates of pediatric AML, while aiming to reduce long-term toxicity.

  6. Hyperdiploidy in Childhood AML Associated with Low Age and AML-M7. A NOPHO-AML Study and Literature Review

    DEFF Research Database (Denmark)

    Sandahl, Julie Damgaard; Abrahamson, Jonas; Heldrup, Jesper

    a literature study searching for hyperdiploid childhood AML (50+) cases using the Mitelman, PubMed, and Scopus databases. The 105 patients from the literature study were compared to the hyperdiploid NOPHO-AML patients. The total cohort of 134 hyperdiploid cases were used to characterize hyperdiploid AML...... to 2010 and with a karyotype including at least one clone with a modal number of 50 or more were identified in the NOPHO-AML database. They were compared to all non-hyperdiploid AML children diagnosed in the Nordic countries and treated according to same NOPHO protocols. Furthermore we conducted...... in children Results: Clinical: The 29 hyperdiploid patients from the population based NOPHO-AML database constituted 6% of all childhood AML cases. Compared to all other NOPHO-AML patients, the hyperdiploid had similar sex distribution (45% boys) but were younger, median age 3 years vs. 6.5, had a lower WBC...

  7. Iron overload in myelodysplastic syndromes (MDS).

    Science.gov (United States)

    Gattermann, Norbert

    2018-01-01

    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.

  8. Utility of 5-Methylcytosine Immunohistochemical Staining to Assess Global DNA Methylation and Its Prognostic Impact in MDS Patients

    Science.gov (United States)

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

    2017-12-29

    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

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

    Directory of Open Access Journals (Sweden)

    David eSallman

    2014-09-01

    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.

  10. Rational Combinations of Targeted Agents in AML

    Directory of Open Access Journals (Sweden)

    Prithviraj Bose

    2015-04-01

    Full Text Available Despite modest improvements in survival over the last several decades, the treatment of AML continues to present a formidable challenge. Most patients are elderly, and these individuals, as well as those with secondary, therapy-related, or relapsed/refractory AML, are particularly difficult to treat, owing to both aggressive disease biology and the high toxicity of current chemotherapeutic regimens. It has become increasingly apparent in recent years that coordinated interruption of cooperative survival signaling pathways in malignant cells is necessary for optimal therapeutic results. The modest efficacy of monotherapy with both cytotoxic and targeted agents in AML testifies to this. As the complex biology of AML continues to be elucidated, many “synthetic lethal” strategies involving rational combinations of targeted agents have been developed. Unfortunately, relatively few of these have been tested clinically, although there is growing interest in this area. In this article, the preclinical and, where available, clinical data on some of the most promising rational combinations of targeted agents in AML are summarized. While new molecules should continue to be combined with conventional genotoxic drugs of proven efficacy, there is perhaps a need to rethink traditional philosophies of clinical trial development and regulatory approval with a focus on mechanism-based, synergistic strategies.

  11. Epigenetic priming of AML blasts for all-trans retinoic acid-induced differentiation by the HDAC class-I selective inhibitor entinostat.

    Directory of Open Access Journals (Sweden)

    Nadja Blagitko-Dorfs

    Full Text Available All-trans retinoic acid (ATRA has only limited single agent activity in AML without the PML-RARα fusion (non-M3 AML. In search of a sensitizing strategy to overcome this relative ATRA resistance, we investigated the potency of the HDAC class-I selective inhibitor entinostat in AML cell lines Kasumi-1 and HL-60 and primary AML blasts. Entinostat alone induced robust differentiation of both cell lines, which was enhanced by the combination with ATRA. This "priming" effect on ATRA-induced differentiation was at least equivalent to that achieved with the DNA hypomethylating agent decitabine, and could overall be recapitulated in primary AML blasts treated ex vivo. Moreover, entinostat treatment established the activating chromatin marks acH3, acH3K9, acH4 and H3K4me3 at the promoter of the RARβ2 gene, an essential mediator of retinoic acid (RA signaling in different solid tumor models. Similarly, RARβ2 promoter hypermethylation (which in primary blasts from 90 AML/MDS patients was surprisingly infrequent could be partially reversed by decitabine in the two cell lines. Re-induction of the epigenetically silenced RARβ2 gene was achieved only when entinostat or decitabine were given prior to ATRA treatment. Thus in this model, reactivation of RARβ2 was not necessarily required for the differentiation effect, and pharmacological RARβ2 promoter demethylation may be a bystander phenomenon rather than an essential prerequisite for the cellular effects of decitabine when combined with ATRA. In conclusion, as a "priming" agent for non-M3 AML blasts to the differentiation-inducing effects of ATRA, entinostat is at least as active as decitabine, and both act in part independently from RARβ2. Further investigation of this treatment combination in non-M3 AML patients is therefore warranted, independently of RARβ2 gene silencing by DNA methylation.

  12. Lessons from the atomic bomb about secondary MDS.

    Science.gov (United States)

    Hata, Tomoko; Imanishi, Daisuke; Miyazaki, Yasushi

    2014-12-01

    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.

  13. 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.

    Science.gov (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

    2016-01-01

    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

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

    OpenAIRE

    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

    2016-01-01

    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, t...

  15. Unraveling the Pathogenesis of MDS: The NLRP3 Inflammasome and Pyroptosis Drive the MDS Phenotype.

    Science.gov (United States)

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

    2016-01-01

    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.

  16. AML (Advanced Mud Logging: First Among Equals

    Directory of Open Access Journals (Sweden)

    T. Loermans

    2017-09-01

    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”.

  17. Treatment strategies in patients with AML or high-risk myelodysplastic syndrome relapsed after Allo-SCT.

    Science.gov (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

    2015-04-01

    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.

  18. 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.

    Science.gov (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

    2016-01-01

    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

  19. Downregulation of MMP1 in MDS-derived mesenchymal stromal cells reduces the capacity to restrict MDS cell proliferation.

    Science.gov (United States)

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

    2017-03-06

    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.

  20. Management of older adults with myelodysplastic syndromes (MDS).

    Science.gov (United States)

    Luskin, Marlise R; Abel, Gregory A

    2017-12-28

    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.

  1. Construction of new quantum MDS codes derived from constacyclic codes

    Science.gov (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.

  2. BCL-2 inhibition with ABT-737 prolongs survival in an NRAS/BCL-2 mouse model of AML by targeting primitive LSK and progenitor cells.

    Science.gov (United States)

    Beurlet, Stephanie; Omidvar, Nader; Gorombei, Petra; Krief, Patricia; Le Pogam, Carole; Setterblad, Niclas; de la Grange, Pierre; Leboeuf, Christophe; Janin, Anne; Noguera, Maria-Elena; Hervatin, Florence; Sarda-Mantel, Laure; Konopleva, Marina; Andreeff, Michael; Tu, Andrea W; Fan, Alice C; Felsher, Dean W; Whetton, Anthony; Pla, Marika; West, Robert; Fenaux, Pierre; Chomienne, Christine; Padua, Rose Ann

    2013-10-17

    Myelodysplastic syndrome (MDS) transforms into an acute myelogenous leukemia (AML) with associated increased bone marrow (BM) blast infiltration. Using a transgenic mouse model, MRP8[NRASD12/hBCL-2], in which the NRAS:BCL-2 complex at the mitochondria induces MDS progressing to AML with dysplastic features, we studied the therapeutic potential of a BCL-2 homology domain 3 mimetic inhibitor, ABT-737. Treatment significantly extended lifespan, increased survival of lethally irradiated secondary recipients transplanted with cells from treated mice compared with cells from untreated mice, with a reduction of BM blasts, Lin-/Sca-1(+)/c-Kit(+), and progenitor populations by increased apoptosis of infiltrating blasts of diseased mice assessed in vivo by technicium-labeled annexin V single photon emission computed tomography and ex vivo by annexin V/7-amino actinomycin D flow cytometry, terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling, caspase 3 cleavage, and re-localization of the NRAS:BCL-2 complex from mitochondria to plasma membrane. Phosphoprotein analysis showed restoration of wild-type (WT) AKT or protein kinase B, extracellular signal-regulated kinase 1/2 and mitogen-activated protein kinase patterns in spleen cells after treatment, which showed reduced mitochondrial membrane potential. Exon specific gene expression profiling corroborates the reduction of leukemic cells, with an increase in expression of genes coding for stem cell development and maintenance, myeloid differentiation, and apoptosis. Myelodysplastic features persist underscoring targeting of BCL-2-mediated effects on MDS-AML transformation and survival of leukemic cells.

  3. Are the MDS-UPDRS-based composite scores clinically applicable?

    Science.gov (United States)

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

    2018-02-28

    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.

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

    Science.gov (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

    2016-09-27

    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.

  5. 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.

    Science.gov (United States)

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

    2017-10-01

    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.

  6. Impact of baseline cytogenetic findings and cytogenetic response on outcome of high-risk myelodysplastic syndromes and low blast count AML treated with azacitidine.

    Science.gov (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

    2017-12-01

    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.

  7. New study reveals relatively few mutations in AML genomes - TCGA

    Science.gov (United States)

    Investigators for The Cancer Genome Atlas (TCGA) Research Network have detailed and broadly classified the genomic alterations that frequently underlie the development of acute myeloid leukemia (AML).

  8. Coaching und Psychotherapie: Grenzen und Gemeinsamkeiten

    OpenAIRE

    Grimmer, B; Neukom, M

    2010-01-01

    Zu den Gemeinsamkeiten und Unterschieden von Coaching und Psychotherapie gab es bisher keine wissenschaftlichen Studien. Vor allem in der Coaching-Literatur wird zwar immer wieder eine klare Abgrenzung beider Verfahren gefordert und ihre Unterschiedlichkeit und Eigenständigkeit betont. Dabei wird argumentiert, dass die Trennungslinie zwischen gesund (Coaching) und krank (Psychotherapie) verläuft, aber ohne diese Gegenüberstellung weiter zu problematisieren oder wissenschaftlich zu analysie...

  9. Immigration und Integration

    OpenAIRE

    Rauscher, Anton

    2003-01-01

    Immigration und Integration : eine Herausforderung für Kirche, Gesellschaft und Politik in Deutschland und den USA / hrsg. von Anton Rauscher. - Berlin : Duncker & Humblot, 2003. - 174 S. - (Soziale Orientierung ; 15)

  10. An Exercise in Extrapolation: Clinical Management of Atypical CML, MDS/MPN-Unclassifiable, and MDS/MPN-RS-T.

    Science.gov (United States)

    Talati, Chetasi; Padron, Eric

    2016-12-01

    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.

  11. [AML treatment strategy based on cytogenetic abnormalities and somatic mutations].

    Science.gov (United States)

    Imai, Yoichi

    2015-10-01

    In addition to morphological and histocytochemical analyses of acute myeloid leukemia (AML), data on cytogenetic abnormalities and somatic mutations are used for classification of AML. The risk stratification based on these examinations facilitates determining the treatment strategy for AML. Cytogenetic risk category definitions by the Southwest Oncology Group (SWOG), Cancer and Leukemia Group B (CALGB), and The Medical Research Council (MRC) classify AML patients into favorable, intermediate, and adverse groups. Approximately 80% of patients in the intermediate group have a normal karyotype and the importance of molecular genetic analyses in these patients is increasing. Somatic mutations of NPM1, CEBPA, and FLT3 are known to be related to the prognosis of AML patients. The European LeukemiaNet (ELN) introduced risk stratification for AML patients based on cytogenetic abnormalities and NPM1, CEBPA, and FLT3 mutations. This risk stratification can be used to select only chemotherapy or chemotherapy with allogeneic hematopoietic stem cell transplantation as consolidation therapy for individual AML patients. Development of molecular targeted therapies against FLT3 or IDH mutations is in progress and these novel therapies are expected to contribute to improving the prognosis of AML patients.

  12. SYK regulates mTOR signaling in AML.

    Science.gov (United States)

    Carnevale, J; Ross, L; Puissant, A; Banerji, V; Stone, R M; DeAngelo, D J; Ross, K N; Stegmaier, K

    2013-11-01

    Spleen tyrosine kinase (SYK) was recently identified as a new target in acute myeloid leukemia (AML); however, its mechanistic role in this disease is poorly understood. Based on the known interaction between SYK and mammalian target of rapamycin (mTOR) signaling in lymphoma, we hypothesized that SYK may regulate mTOR signaling in AML. Both small-molecule inhibition of SYK and SYK-directed shRNA suppressed mTOR and its downstream signaling effectors, as well as its upstream activator, AKT. Moreover, the inhibition of multiple nodes of the phosphatidylinositol 3'-kinase (PI3K) signaling pathway enhanced the effects of SYK suppression on AML cell viability and differentiation. Evaluation of the collateral mitogen-activated protein kinase (MAPK) pathway revealed a heterogeneous response to SYK inhibition in AML with downregulation of MEK and extracellular signal-regulated kinase (ERK) phosphorylation in some AML cell lines but a paradoxical increase in MEK/ERK phosphorylation in RAS-mutated AML. These studies reveal SYK as a regulator of mTOR and MAPK signaling in AML and demonstrate that inhibition of PI3K pathway activity enhances the effects of SYK inhibition on AML cell viability and differentiation.

  13. Nassi-Schneiderman Diagram in HTML Based on AML

    Science.gov (United States)

    Menyhárt, László

    2013-01-01

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

    Science.gov (United States)

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

    2018-02-01

    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.

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

    Science.gov (United States)

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

    2018-03-01

    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.

  16. Progress in the diagnosis of and therapy for MDS.

    Science.gov (United States)

    Nannya, Yasuhito

    2016-01-01

    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.

  17. MDS clinical diagnostic criteria for Parkinson's disease in China.

    Science.gov (United States)

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

    2017-03-01

    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.

  18. MDS. A disease with high radiation-risk

    International Nuclear Information System (INIS)

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

    2003-01-01

    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)

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

    Science.gov (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

    2017-07-01

    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: journals.permissions@oup.com

  20. [Clinical Significance of ID4 Gene Mehtylation in Demethylation-Treated MDS Cell Line and 2 MDS Patients].

    Science.gov (United States)

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

    2015-04-01

    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.

  1. Verantwortlichkeits- und Schuldzuschreibungen bei Ost- und Westdeutschen

    OpenAIRE

    Janetzko, Elke; Schmitt, Manfred

    1992-01-01

    An einer Stichprobe von 140 Westdeutschen und 147 Ostdeutschen wurde die Hypothese untersucht, ob Ostdeutsche aufgrund der restriktiven gesellschaftlichen Rahmenbedingungen in der DDR zu geringeren Selbstzuschreibungen von Verantwortlichkeit und Schuld bei Schadensereignissen des öffentlichen Lebens neigen als Westdeutsche. In einem experimentellen Fragebogen wurden vier Schadensszenarien geschildert, zwei aus dem privaten (Auto, Schrebergarten) und zwei aus dem öffentlichen Leben (Trinkwasse...

  2. Resident Assessment Instrument/Minimum Data Set (RAI/MDS)

    Data.gov (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...

  3. MDS 2.0 Public Quality Indicator and Resident Reports

    Data.gov (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...

  4. Physikdidaktik Theorie und Praxis

    CERN Document Server

    Girwidz, Raimund; Häußler, Peter

    2015-01-01

    „Physikdidaktik – Theorie und Praxis“ ist ein Sammelband, der dynamisch gewachsen ist. Der Teil I wurde im Jahre 2000 in erster Linie für Studierende des Lehramts Physik konzipiert. Der Teil II zeigt Konkretisierungen und im Unterricht erprobte Beispiele zu neueren didaktischen und methodischen Ansätzen, die aus der Pädagogik und der allgemeinen Didaktik für die Physikdidaktik aufbereitet wurden. Die Physikdidaktik befasst sich natürlich auch mit der Frage, welche Elemente aus der modernen Physik in den Unterricht eingehen können und sollen. Vor der Aufbereitung der Inhalte für den Unterricht, mit Vereinfachungen und angemessenen didaktischen Reduktionen, steht die Sachanalyse und die Zusammenfassung von interessanten Themen aus aktuellen experimentellen und theoretischen Arbeitsgebieten der Physik (Teil III). In der vorliegenden 3. Ausgabe eines Gesamtbandes „Physikdidaktik – Theorie und Praxis“ wurden Astrophysik, Elementar­teilchenphysik und Biophysik als interessante Beispiele aus ...

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

    Science.gov (United States)

    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

    2016-01-01

    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 (PP= 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. PMID:27527853

  6. Gene-Specific Demethylation as Targeted Therapy in MDS

    Science.gov (United States)

    2017-07-01

    AWARD NUMBER: W81XWH-15-1-0161 TITLE: Gene-Specific Demethylation as Targeted Therapy in MDS PRINCIPAL INVESTIGATOR: Daniel G. Tenen, M.D...15JUN2016-14JUN2017 4. TITLE AND SUBTITLE Gene-Specific Demethylation as Targeted Therapy in MDS 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM... magnetic beads capture all newly synthesized transcripts. To compare the transcriptional profiles under these conditions with our previous results, we

  7. New constructions of MDS codes with complementary duals

    OpenAIRE

    Chen, Bocong; Liu, Hongwei

    2017-01-01

    Linear complementary-dual (LCD for short) codes are linear codes that intersect with their duals trivially. LCD codes have been used in certain communication systems. It is recently found that LCD codes can be applied in cryptography. This application of LCD codes renewed the interest in the construction of LCD codes having a large minimum distance. MDS codes are optimal in the sense that the minimum distance cannot be improved for given length and code size. Constructing LCD MDS codes is thu...

  8. An improved resource management model based on MDS

    Science.gov (United States)

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

    2005-11-01

    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.

  9. Myelodysplastic Syndromes (MDS) and autoimmune disorders (AD): cause or consequence?

    Science.gov (United States)

    Braun, Thorsten; Fenaux, Pierre

    2013-12-01

    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.

  10. Treatment strategy and long-term results in paediatric patients treated in consecutive UK AML trials.

    NARCIS (Netherlands)

    Gibson, B.E.; Wheatley, K.; Hann, I.M.; Stevens, R.F.; Webb, D.; Hills, R.K.; Graaf, S.S.N. de; Harrison, C.J.

    2005-01-01

    Between 1988 and 2002, 758 children with acute myeloid leukaemia (AML) were treated on Medical Research Council (MRC) AML 10 and AML 12. MRC AML 10 tested the role of bone marrow transplantation following four blocks of intensive chemotherapy and found that while both allogeneic bone marrow

  11. Proteomic and Genetic Approaches Identify Syk as an AML Target

    Science.gov (United States)

    Hahn, Cynthia K.; Berchuck, Jacob E.; Ross, Kenneth N.; Kakoza, Rose M.; Clauser, Karl; Schinzel, Anna C.; Ross, Linda; Galinsky, Ilene; Davis, Tina N.; Silver, Serena J.; Root, David E.; Stone, Richard M.; DeAngelo, Daniel J.; Carroll, Martin; Hahn, William C.; Carr, Steven A.; Golub, Todd R.; Kung, Andrew L.; Stegmaier, Kimberly

    2009-01-01

    SUMMARY Cell-based screening can facilitate rapid identification of compounds inducing complex cellular phenotypes. Advancing a compound toward the clinic, however, generally requires identification of precise mechanisms of action. We previously found that epidermal growth factor receptor (EGFR) inhibitors induce acute myeloid leukemia (AML) differentiation via a non-EGFR mechanism. In this report, we integrated proteomic and RNAi-based strategies to identify their off-target anti-AML mechanism. These orthogonal approaches identified Syk as a target in AML. Genetic and pharmacological inactivation of Syk with a drug in clinical trial for other indications promoted differentiation of AML cells and attenuated leukemia growth in vivo. These results demonstrate the power of integrating diverse chemical, proteomic, and genomic screening approaches to identify therapeutic strategies for cancer. PMID:19800574

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

    Directory of Open Access Journals (Sweden)

    Diamantina Vasilatou

    2014-01-01

    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.

  13. 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.

    2017-01-01

    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

  14. Information und Kommunikation

    Science.gov (United States)

    Wesoly, Michael; Ohlhausen, Peter; Bucher, Michael; Hichert, Rolf; Korge, Gabriele; Schnabel, Ulrich; Gairola, Arun; Reichwald, Ralf; Habicht, Hagen; Möslein, Kathrin; Schwarz, Torsten; Schönsleben, Paul; Scherer, Eric; Schloske, Alexander; Adlbrecht, Gerald; Federhen, Jens

    Wissen ist mittlerweile unverzichtbar für den entscheidenden Vorsprung auf dem Markt. Unabhängig davon, ob sich das Wissen in Innovationen, neuen Produkten und Dienstleistungen oder in der Verbesserung interner Unternehmensprozesse manifestiert: Wissen ist Treiber von Innovation, Wissen bringt Schnelligkeit und Wissen ist die Voraussetzung für Problemlösungen [40]. Wissensmanagement ist daher der Schlüssel für Unternehmenserfolg und bezeichnet den "bewussten und systematischen Umgang mit der Ressource Wissen und den zielgerichteten Einsatz von Wissen in der Organisation“ [6]. In dieser umfassenden Sichtweise ist Wissensmanagement ein Begriff, der Konzepte, Strategien und Methoden umfasst.

  15. Westliche und muslimische Geschlechter?

    Directory of Open Access Journals (Sweden)

    Stanislawa Paulus

    2008-11-01

    Full Text Available Mihçiyazgan geht der Frage nach wie Differenzen in männlichen und weiblichen Subjektkonstutionen im Westen und im Islam empirisch erfasst werden können. Hierbei verfolgt sie eine antiessentialitische Perspektive, in der sie sich zentral auf Judith Butler und Michel Foucault bezieht. Über beide hinausgehend entwickelt sie ein Modell pluraler Diskurse, mit dessen Hilfe kulturelle bedingte Geschlechterkonstruktionen verstehbar werden. Anhand einer Untersuchung von Interviews, in der sie interaktionsanalytische und diskursanalytische Herangehensweisen verbindet, macht sie unterschiedliche Zonen des Sagbaren und Unsagbaren in westlichen und muslimischen Geschlechterdiskursen sichtbar.

  16. 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.

    2016-01-01

    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

  17. Infektionsepidemiologische Ausbildungs- und Trainingsprogramme FETP und EPIET

    OpenAIRE

    Bremer, Viviane

    2005-01-01

    Das deutsche Field Epidemiology Training Pro gramme (FETP) und das europäische European Programme for Intervention Epidemiology Training (EPIET) wurden gegründet, um ein Netzwerk von Epidemiologen für die Überwachung und Kontrolle von Infektionskrankheiten auszubilden. Innerhalb von 2 Jahren müssen die Trainees am Robert Koch-Institut oder an europäischen Gastinstituten Ausbruchsuntersuchungen, Surveillance- und Forschungsprojekte durchführen und die Ergebnisse veröffentlichen. Seit 1995 habe...

  18. Macht und Architektur

    DEFF Research Database (Denmark)

    Nagbøl, Søren Peter

    2015-01-01

    Unser Thema ist „Macht und Architektur“. Wir wollen die sozialen Beziehungen betrachten, die Menschen und Architektur miteinander eingehen. Indem wir versuchen, Architektur erlebnisanalytisch zu interpretieren, wollen wir auf die Bedeutungen aufmerksam machen, die die Formensprache der Architektu...

  19. Safety Study of AG-120 or AG-221 in Combination With Induction and Consolidation Therapy in Patients With Newly Diagnosed Acute Myeloid Leukemia With an IDH1 and/or IDH2 Mutation

    Science.gov (United States)

    2018-02-22

    Newly Diagnosed Acute Myeloid Leukemia (AML); Untreated AML; AML Arising From Myelodysplastic Syndrome (MDS); AML Arising From Antecedent Hematologic Disorder (AHD); AML Arising After Exposure to Genotoxic Injury

  20. 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

    2006-01-01

    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

  1. Differential Analysis of Genetic, Epigenetic, and Cytogenetic Abnormalities in AML

    Directory of Open Access Journals (Sweden)

    Mirazul Islam

    2017-01-01

    Full Text Available Acute myeloid leukemia (AML is a haematological malignancy characterized by the excessive proliferation of immature myeloid cells coupled with impaired differentiation. Many AML cases have been reported without any known cytogenetic abnormalities and carry no mutation in known AML-associated driver genes. In this study, 200 AML cases were selected from a publicly available cohort and differentially analyzed for genetic, epigenetic, and cytogenetic abnormalities. Three genes (FLT3, DNMT3A, and NPMc are found to be predominantly mutated. We identified several aberrations to be associated with genome-wide methylation changes. These include Del (5q, T (15; 17, and NPMc mutations. Four aberrations—Del (5q, T (15; 17, T (9; 22, and T (9; 11—are significantly associated with patient survival. Del (5q-positive patients have an average survival of less than 1 year, whereas T (15; 17-positive patients have a significantly better prognosis. Combining the methylation and mutation data reveals three distinct patient groups and four clusters of genes. We speculate that combined signatures have the better potential to be used for subclassification of AML, complementing cytogenetic signatures. A larger sample cohort and further investigation of the effects observed in this study are required to enable the clinical application of our patient classification aided by DNA methylation.

  2. Kinder- und Jugendfilmanalyse

    NARCIS (Netherlands)

    Kurwinkel, T.; Schmerheim, P.

    2013-01-01

    Dieser Band stellt erstmalig einen methodischen Ansatz zur Analyse des Kinder- und Jugendfilms vor. Er berücksichtigt dabei die Besonderheiten der kindlichen und jugendlichen Filmrezeption: So neigen Kinder in höherem Maße als Erwachsene dazu, einen Film erlebnisorientiert und emotional

  3. Volasertib for AML: clinical use and patient consideration

    Directory of Open Access Journals (Sweden)

    Hao Z

    2015-07-01

    Full Text Available Zhonglin Hao,1 Vamsi Kota2 1Cancer Center, Medical College of Georgia, Georgia Regents University, Augusta, GA, USA; 2Winship Cancer Institute, Emory University School of Medicine, Atlanta, GA, USA Abstract: Acute myeloid leukemia (AML is a disease diagnosed mostly in patients >65 years of age. Despite its heterogeneous nature, the different types of AMLs are still managed by standard induction chemotherapy for those who can tolerate it in the beginning. For the elderly and infirm patients, however, this approach leads to unacceptably high induction mortality rate. This article reviews past and current efforts searching for low-intensiveness treatments for the elderly and infirm patients who cannot tolerate the standard induction regimen. Volasertib, currently in Phase III clinical trials in combination with cytarabine, is reviewed as a promising agent for this patient population with AML, from the viewpoints of potential compliance and efficacy. Keywords: volasertib, acute myeloid leukemia, management, induction

  4. Outcome of poor response Paediatric AML using early SCT

    DEFF Research Database (Denmark)

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

    2013-01-01

    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......) 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...

  5. Cellular origin of prognostic chromosomal aberrations in AML patients

    DEFF Research Database (Denmark)

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

    2015-01-01

    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......Acute myeloid leukemia (AML) represents an aggressive cancer entity, whose malignant cells respond abnormally to regulatory stimuli and have lost the ability to differentiate and become fully mature blood cells.1, 2 AML evolves through accumulation of independent genetic aberrations, including...... karyotype have demonstrated the presence of prognostic driver aberrations (that is, NPM1, FLT3-ITD and FLT3-TKD) in committed HPCs but not in multipotent HSCs. However, the HSC populations lacking the prognostic driver aberrations contained preleukemic clones harboring a series of recurrent molecular...

  6. SIMILARITIES OF ELDERLY AND THERAPY-RELATED AML

    Directory of Open Access Journals (Sweden)

    Francesco D'Alò

    2011-11-01

    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

  7. Romanistik und gender studies

    Directory of Open Access Journals (Sweden)

    Susanne Schlünder

    2000-11-01

    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.

  8. 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.

    2008-01-01

    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

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

    Science.gov (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

    2015-03-01

    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.

  10. Monitoring treatment efficiency in MDS at the molecular level; possibilities now and in the future.

    NARCIS (Netherlands)

    Dijk, J.P. van; Witte, T.J.M. de

    2004-01-01

    Myelodysplastic syndromes (MDS) are a heterogeneous group of bone marrow (BM) diseases. MDS patients suffer from bone marrow failure because of the expansion of a malignant clone, resulting in abnormal differentiation of blood cells and severe pancytopenias. MDS patients have a high propensity for

  11. 75 FR 16512 - Willstaff Staffing Agency, Willstaff Crystal, Inc., and MDS Industrial Resources, Inc., Working...

    Science.gov (United States)

    2010-04-01

    ... 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...

  12. Some Families of Asymmetric Quantum MDS Codes Constructed from Constacyclic Codes

    Science.gov (United States)

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

    2018-02-01

    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

  13. Handling missing values in the MDS-UPDRS.

    Science.gov (United States)

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

    2015-10-01

    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.

  14. Comparing leukapheresis protocols for an AML patient with symptomatic leukostasis.

    Science.gov (United States)

    Cline, Abigail; Jajosky, Ryan; Shikle, James; Bollag, Roni

    2017-09-22

    Acute myeloid leukemia (AML) is a malignancy characterized by rapid clonal proliferation of myeloid precursors, which can result in hyperleukocytosis. Leukapheresis can be used to rapidly reduce the white blood cell count (WBC). However, the only FDA cleared device for WBC depletion, the COBE Spectra, will no longer be supported by the manufacturer in 2017, and there are few studies comparing different methods of leukapheresis. A 68-year-old African American female was admitted to the hospital for relapse of her AML. Laboratory data demonstrated a WBC count of 291 600/μL and flow cytometry of the peripheral blood demonstrated 85% myeloid blasts. Leukapheresis was ordered to help treat the leukostasis. Three different apheresis protocols were used to achieve cytoreduction: Spectra Optia mononuclear collection (MNC) protocol, Spectra Optia granulocyte collection (PMN) protocol, and Therakos CELLEX buffy coat collection without return. Due to different inlet flow rates, the procedures were evaluated based on the number of WBCs collected and volume of blood processed (VBP). The Spectra Optia PMN collected the most WBCs and collected nearly as many WBCs per VBP as the Therakos CELLEX, which had the highest value. To our knowledge, we are reporting the first use of Therakos CELLEX and Spectra Optia PMN protocol for WBC depletion. While the Spectra Optia granulocyte protocol showed the best performance for this AML patient, further studies will be needed to compare the Spectra Optia PMN protocol to the MNC protocol for AML patients. © 2017 Wiley Periodicals, Inc.

  15. Outcome of poor response paediatric AML using early SCT.

    Science.gov (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

    2013-03-01

    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. Krieg und Literatur

    Directory of Open Access Journals (Sweden)

    Elfi N. Theis

    2007-03-01

    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.

  17. The need for additional genetic markers for MDS stratification: what does the future hold for prognostication?

    Science.gov (United States)

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

    2013-01-01

    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

  18. To chelate or not to chelate in MDS: That is the question!

    Science.gov (United States)

    Zeidan, Amer M; Griffiths, Elizabeth A

    2018-03-08

    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.

  19. Vorwort und Editorial

    OpenAIRE

    Gramlinger, Franz; Moser, Daniela; Schlögl, Peter; Dorninger, Christian; Schmid, Kurt; Stock, Michaela

    2017-01-01

    Auch wenn (berufs-)bildungspolitische Diskussionen um Gleichwertigkeit, Durchlässigkeit, Anerkennung und aktuell um Verberuflichung des Akademischen und Akademisierung des Beruflichen eine Annäherung allgemeiner und beruflicher Bildung vermuten lassen, ist die Frage nach dem Verhältnis dieser beiden Bildungen nicht eindeutig gelöst. Vielmehr stehen nach wie vor unterschiedliche Positionen nebeneinander. Im folgenden Beitrag geht es weniger um die Frage danach, was beide Bildungen eint, trennt...

  20. Fotografie und atomare Katastrophe

    OpenAIRE

    Bürkner, Daniel

    2015-01-01

    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...

  1. Psychotherapie und Internet

    OpenAIRE

    Barthel, Christoph

    2009-01-01

    In der vorliegenden Arbeit werden Hintergründe und Möglichkeiten internetbasierter Therapie- und Beratungsmöglichkeiten aufgezeigt. Darüber hinaus wird ein vom Autor selbst durchgeführtes Projekt internetbezogener Beratung vorgestellt. Neben der Geschichte des Internets werden verschiedene Kommunikationstheorien vorgestellt und mit dem heutigen Status Quo verglichen. Ferner wird die Rolle des Internets in der Psychotherapie beleuchtet, sowie die sich hieraus ergebenen Qualitätsstandards...

  2. Zwergsatelliten und Sternriesen

    Science.gov (United States)

    Baade, Dietrich; Kuschnig, Rainer

    2017-03-01

    Leuchtkräftige Sterne sind schwierig: Fär Fotometrie mit großen Teleskopen sind sie zu hell, und ihre geringe Zahl macht konventionelle Lösungen unwirtschaftlich, besonders im Weltraum, wo die äußerste Präzision gegeben wäre. Mit einer Mini-Armada von Nanosatelliten haben Ingenieure und Astronomen aus Kanada, Österreich und Polen nun die Lösung gefunden - auch schon für viele wissenschaftliche Fragen.

  3. Zwischen Empire und Empower : Dekolonisierung und Demokratisierung

    OpenAIRE

    Dhawan, Nikita

    2011-01-01

    In ihrem Buch "Cultivating Humanity" formuliert Martha Nussbaum folgenden Appell: "(…) die Welt um uns herum ist unausweichlich international. Themen vom Handel bis zur Landwirtschaft – über die Menschenrechte bis hin zu der Linderung von Hungersnöten – fordern uns dazu heraus, den Blick über eng gefasste Gruppenloyalitäten hinaus zu wagen und weit entfernte Lebenswirklichkeiten zu berücksichtigen. (…) Die Kultivierung unserer Menschlichkeit in einer komplexen und ineinander verflochtenen Wel...

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

    DEFF Research Database (Denmark)

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

    2016-01-01

    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......;11). Trisomy 8 alone was associated with older age (median age 10.1 years), FAB M2 (33%), and FLT3-ITD mutations (58%). The 5-year event-free survival for patients with +8 alone was 50% and 5-year overall survival was 75%. In conclusion, +8 is one of the most common cytogenetic aberrations in pediatric AML...

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

    Science.gov (United States)

    El-Fattah, Mohamed Abd

    2018-01-01

    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.

  6. Entanglement-assisted quantum MDS codes from negacyclic codes

    Science.gov (United States)

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

    2018-03-01

    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.

  7. 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

    2010-01-01

    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...

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

    International Nuclear Information System (INIS)

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

    1994-01-01

    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

  9. Milch, Milchprodukte, Analoge und Speiseeis

    Science.gov (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.

  10. Übergewicht und Adipositas in Kindheit und Jugend

    OpenAIRE

    Nitzko, Sina

    2010-01-01

    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...

  11. Wissensmanagement und Medienbildung - neue Spannungsverhältnisse und Herausforderungen

    Directory of Open Access Journals (Sweden)

    Gabi Reinmann

    2005-05-01

    Full Text Available Begrifflichkeiten schaffen Bewusstsein, haben Wirkungen auf Denken und Handeln und können Zielsetzungen von morgen beeinflussen. Der vorliegende Beitrag möchte der Frage nachgehen, welche Funktion der Begriff des Wissensmanagements in pädagogischen Kontexten hat und künftig haben wird, welche Chancen und Risiken davon ausgehen und in welchem Verhältnis er zum Begriff der Medienbildung steht oder stehen könnte.

  12. Steuern und Governance

    Directory of Open Access Journals (Sweden)

    Eduard Müller

    2014-05-01

    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.

  13. Gesundheit, Essen und Nachhaltigkeit

    DEFF Research Database (Denmark)

    Reisch, Lucia

    2012-01-01

    zwischen Gesundheit, Essen und Nachhaltigkeit geht der Auftrag der Ernährungsaufklärung heute thematisch über den der klassischen Aufklärung hinaus. Vor diesem Hintergrund beschäftigt sich der Beitrag mit den Fragen, wie heute eine „gesunde, nachhaltige Ernährung“ - und damit das Ziel einer gelingenden...

  14. Thermodynamik grundlagen und technische anwendungen

    CERN Document Server

    Baehr, Hans Dieter

    2009-01-01

    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...

  15. 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

  16. Genotype-outcome correlations in pediatric AML: the impact of a monosomal karyotype in trial AML-BFM 2004

    Science.gov (United States)

    Rasche, M; von Neuhoff, C; Dworzak, M; Bourquin, J-P; Bradtke, J; Göhring, G; Escherich, G; Fleischhack, G; Graf, N; Gruhn, B; Haas, O A; Klingebiel, T; Kremens, B; Lehrnbecher, T; von Stackelberg, A; Tchinda, J; Zemanova, Z; Thiede, C; von Neuhoff, N; Zimmermann, M; Creutzig, U; Reinhardt, D

    2017-01-01

    We conducted a cytogenetic analysis of 642 children with de novo acute myeloid leukemia (AML) treated on the AML-Berlin-Frankfurt-Münster (BFM) 04 protocol to determine the prognostic value of specific chromosomal aberrations including monosomal (MK+), complex (CK+) and hypodiploid (HK+) karyotypes, individually and in combination. Multivariate regression analysis identified in particular MK+ (n=22) as a new independent risk factor for poor event-free survival (EFS 23±9% vs 53±2% for all other patients, P=0.0003), even after exclusion of four patients with monosomy 7 (EFS 28±11%, P=0.0081). CK+ patients without MK had a better prognosis (n=47, EFS 47±8%, P=0.46) than those with MK+ (n=12, EFS 25±13%, P=0.024). HK+ (n=37, EFS 44±8% for total cohort, P=0.3) influenced outcome only when t(8;21) patients were excluded (remaining n=16, EFS 9±8%, Pkaryotype is a strong and independent predictor for high-risk pediatric AML. In addition, isolated trisomy 8 and hypodiploidy without t(8;21) coincide with dismal outcome. These results have important implications for risk stratification and should be further validated in independent pediatric cohorts. PMID:28443606

  17. Beurteilung von nativen und aufgetauten Spermatozoen fertiler und subfertiler Hengste mit Hilfe der Phasenkontrast- und Transmissionselektronenmikroskopie

    OpenAIRE

    Smedts, Ellen

    2012-01-01

    Beurteilung von nativen und aufgetauten Spermatozoen fertiler und subfertiler Hengste mit Hilfe der Phasenkontrast- und Transmissionselektronenmikroskopie. Institut für Veterinär-Pathologie der Veterinärmedizinischen Fakultät, Universität Leipzig Reproduktionsmedizinische Einheit der Kliniken der Tierärztlichen Hochschule Hannover In dieser Arbeit wurde die Ultrastruktur von nativen und tiefgefrorenen Spermien mittels Phasenkontrast- und Transmissionselektronenmikroskopie (TEM) unt...

  18. The Mice Drawer System Tissue Sharing Program (MDS-TSP)

    Science.gov (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

  19. Mediendidaktik und Wissensmanagement

    Directory of Open Access Journals (Sweden)

    Gabi Reinmann-Rothmeier

    2002-10-01

    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.

  20. Insufficient stromal support in MDS results from molecular and functional deficits of mesenchymal stromal cells.

    Science.gov (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

    2013-09-01

    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.

  1. Trauma und Terror

    OpenAIRE

    Szyszkowitz, T. (Tessa)

    2007-01-01

    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...

  2. Targeting Ras signaling in AML: RALB is a small GTPase with big potential.

    Science.gov (United States)

    Pomeroy, Emily J; Eckfeldt, Craig E

    2017-07-06

    Acute myeloid leukemia (AML) is a devastating malignancy for which novel treatment approaches are desperately needed. Ras signaling is an attractive therapeutic target for AML because a large proportion of AMLs have mutations in NRAS, KRAS, or genes that activate Ras signaling, and key Ras effectors are activated in virtually all AML patient samples. This has inspired efforts to develop Ras-targeted treatment strategies for AML. Due to the inherent difficulty and disappointing efficacy of targeting Ras proteins directly, many have focused on inhibiting Ras effector pathways. Inhibiting the major oncogenic Ras effectors, the mitogen-activated protein kinase (MAPK) and/or phosphatidylinositiol-3-kinase (PI3K) pathways, has generally demonstrated modest efficacy for AML. While this may be in part related to functional redundancy between these pathways, it is now clear that other Ras effectors have key oncogenic roles. Specifically, the Ras-like (Ral) GTPases have emerged as critical mediators of Ras-driven transformation and AML cell survival. Our group recently uncovered a critical role for RALB signaling in leukemic cell survival and a potential mediator of relapse following Ras-targeted therapy in AML. Furthermore, we found that RALB signaling is hyperactivated in AML patient samples, and inhibiting RALB has potent anti-leukemic activity in preclinical AML models. While key questions remain regarding the importance of RALB signaling across the genetically diverse spectrum of AML, the specific mechanism(s) that promotes leukemic cell survival downstream of RALB, and how to pharmacologically target RALB signaling effectively - RALB has emerged as a critical Ras effector and potential therapeutic target for AML.

  3. Molecular pathway activation features of pediatric acute myeloid leukemia (AML) and acute lymphoblast leukemia (ALL) cells.

    Science.gov (United States)

    Petrov, Ivan; Suntsova, Maria; Mutorova, Olga; Sorokin, Maxim; Garazha, Andrew; Ilnitskaya, Elena; Spirin, Pavel; Larin, Sergey; Kovalchuk, Olga; Prassolov, Vladimir; Zhavoronkov, Alex; Roumiantsev, Alexander; Buzdin, Anton

    2016-11-19

    Acute lymphoblast leukemia (ALL) is characterized by overproduction of immature white blood cells in the bone marrow. ALL is most common in the childhood and has high (>80%) cure rate. In contrast, acute myeloid leukemia (AML) has far greater mortality rate than the ALL and is most commonly affecting older adults. However, AML is a leading cause of childhood cancer mortality. In this study, we compare gene expression and molecular pathway activation patterns in three normal blood, seven pediatric ALL and seven pediatric AML bone marrow samples. We identified 172/94 and 148/31 characteristic gene expression/pathway activation signatures, clearly distinguishing pediatric ALL and AML cells, respectively, from the normal blood. The pediatric AML and ALL cells differed by 139/34 gene expression/pathway activation biomarkers. For the adult 30 AML and 17 normal blood samples, we found 132/33 gene expression/pathway AML-specific features, of which only 7/2 were common for the adult and pediatric AML and, therefore, age-independent. At the pathway level, we found more differences than similarities between the adult and pediatric forms. These findings suggest that the adult and pediatric AMLs may require different treatment strategies.

  4. Sukzession und Tradition in Antike und Urchristentum

    African Journals Online (AJOL)

    Uber Jakobus berichtet man, dass er das weisse Gewand des. Leviten angelegt habe und es ihm als einzigen gestattet gewesen sei, das Heiligtum zu betreten.io Die Leitung der Kirche in Jerusalem war ein Amt, das in der Familie. Jesu weitergegeben wurde, solange Mitglieder derselben verfiigbar waren.n Die. Ansicht ...

  5. In vitro transformation of primary human CD34+ cells by AML fusion oncogenes: early gene expression profiling reveals possible drug target in AML.

    Directory of Open Access Journals (Sweden)

    Anmaar M Abdul-Nabi

    2010-08-01

    Full Text Available Different fusion oncogenes in acute myeloid leukemia (AML have distinct clinical and laboratory features suggesting different modes of malignant transformation. Here we compare the in vitro effects of representatives of 4 major groups of AML fusion oncogenes on primary human CD34+ cells. As expected from their clinical similarities, MLL-AF9 and NUP98-HOXA9 had very similar effects in vitro. They both caused erythroid hyperplasia and a clear block in erythroid and myeloid maturation. On the other hand, AML1-ETO and PML-RARA had only modest effects on myeloid and erythroid differentiation. All oncogenes except PML-RARA caused a dramatic increase in long-term proliferation and self-renewal. Gene expression profiling revealed two distinct temporal patterns of gene deregulation. Gene deregulation by MLL-AF9 and NUP98-HOXA9 peaked 3 days after transduction. In contrast, the vast majority of gene deregulation by AML1-ETO and PML-RARA occurred within 6 hours, followed by a dramatic drop in the numbers of deregulated genes. Interestingly, the p53 inhibitor MDM2 was upregulated by AML1-ETO at 6 hours. Nutlin-3, an inhibitor of the interaction between MDM2 and p53, specifically inhibited the proliferation and self-renewal of primary human CD34+ cells transduced with AML1-ETO, suggesting that MDM2 upregulation plays a role in cell transformation by AML1-ETO. These data show that differences among AML fusion oncogenes can be recapitulated in vitro using primary human CD34+ cells and that early gene expression profiling in these cells can reveal potential drug targets in AML.

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

    Directory of Open Access Journals (Sweden)

    Fries Brant E

    2005-01-01

    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.

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

    Science.gov (United States)

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

    2005-01-01

    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

  8. Supraleitung Grundlagen und Anwendungen

    CERN Document Server

    Buckel, Werner

    2004-01-01

    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...

  9. Wasserball und Kommunismus

    NARCIS (Netherlands)

    Celikates, R.

    2010-01-01

    Zuletzt recht medienwirksam verbreiten Philosophen wie Slavoj Žižek und Alain Badiou eine vage «kommunistische Hypothese» - wie sehen die Theoriealternativen zu dieser neokommunistischen Intervention aus, die zugleich eine Abkehr vom Marxismus ist?

  10. Ausbildung und Erwartungshaltung

    Science.gov (United States)

    Knoke, Holger

    1997-09-01

    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. Zwischen Freakout und Normcore

    Directory of Open Access Journals (Sweden)

    Beate Großegger

    2017-06-01

    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.

  12. AML with 11q23/MLL abnormalities as defined by the WHO classification: incidence, partner chromosomes, FAB subtype, age distribution, and prognostic impact in an unselected series of 1897 cytogenetically analyzed AML cases.

    Science.gov (United States)

    Schoch, Claudia; Schnittger, Susanne; Klaus, Mirjam; Kern, Wolfgang; Hiddemann, Wolfgang; Haferlach, Torsten

    2003-10-01

    Acute myeloid leukemia (AML) cases with 11q23 abnormalities involving the MLL gene comprise one category of recurring genetic abnormalities in the WHO classification. In an unselected series of 1897 AML cases, 54 patients with an 11q23/MLL rearrangement were identified, resulting in an incidence of 2.8%. The incidence of AML with MLL rearrangement was significantly higher in therapy-related AML (t-AML) than in de novo AML (9.4% vs 2.6%, P FAB) subtypes (P <.0001). Compared with AML with intermediate karyotype, AML with 11q23/MLL rearrangement had a worse outcome, which was rather comparable with AML with unfavorable karyotype. Compared with t-AML, the median overall survival (OS) of de novo AML with MLL rearrangement was significantly better (2.5 vs 10 months, P =.0143). No significant differences in median OS were observed between cases with t(9;11) compared with all other MLL rearrangements (10.0 vs 8.9 months, P =.36). In conclusion, the category AML with 11q23/MLL abnormalities accounts for 2.8% of unselected AML, is closely associated with monocytic differentiation, and has a dismal prognosis. (

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

    Science.gov (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

    2017-06-01

    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.

  14. Improved outcome in childhood acute myeloid leukemia in Singapore with the MRC AML 10 protocol.

    Science.gov (United States)

    Tan, Ronald M; Quah, Thuan Chong; Aung, Lele; Liang, Shen; Kirk, Richard C; Yeoh, Allen E J

    2007-03-01

    The introduction of the United Kingdom Medical Research Council's 10th AML trial (MRC AML 10) protocol incorporating high-dose anthracycline therapy has improved outcome of children with acute myeloid leukemia (AML). In this study, we review the results of childhood AML therapy in a Singapore university hospital over the last 17 years emphasizing toxicity and outcome. Retrospective analysis revealed 34 children with AML between 1988 and 2003. Prior to September 1996, therapy consisted of: POG-8498 (n = 10), others (n = 9). From September 1996, all but one of 15 children received MRC AML 10 treatment. At the time of analysis, 17 had died from disease, and 17 patients were alive among whom 2 had relapsed. MRC AML 10-treated patients (n = 14) had significantly better 3-year overall, event-free, and disease-free survival (74% vs. 35%, 77% vs. 20%, 83% vs. 31%; P = 0.019, P = 0.002, and P = 0.010, respectively) and were likelier to achieve complete remission (CR) than non-MRC AML 10 patients (P = 0.102). Among patients who achieved CR, MRC AML 10-treated patients were significantly more likely to achieve CR after only one cycle of chemotherapy (P = 0.016). Hematologic toxicity was similar among the different regimens (P = 0.9). These findings suggest that MRC AML 10 treatment results in significantly superior survival, without excess toxicity. Future studies should attempt to elucidate the relative importance of individual MRC AML 10 components and reduce the high cumulative anthracycline dose without compromising outcome. (c) 2006 Wiley-Liss, Inc.

  15. 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

    2015-03-01

    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.

  16. 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.

    2015-01-01

    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

  17. Minimal clinically important difference on the Motor Examination part of MDS-UPDRS.

    Science.gov (United States)

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

    2015-12-01

    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.

  18. 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.

    2016-01-01

    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

  19. New q-ary quantum MDS codes with distances bigger than q/2

    Science.gov (United States)

    He, Xianmang; Xu, Liqing; Chen, Hao

    2016-07-01

    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

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

    DEFF Research Database (Denmark)

    Paasch, Uwe; Schwandt, Antje; Seeber, Nikolaus

    2017-01-01

    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 ...

  1. Therapy with low-dose azacitidine for MDS in children and young adults: a retrospective analysis of the EWOG-MDS study group.

    Science.gov (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

    2016-03-01

    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.

  2. Netzformen und VDE-Bestimmungen

    Science.gov (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.

  3. Nichtlineare Faseroptik Grundlagen und Anwendungsbeispiele

    CERN Document Server

    Engelbrecht, Rainer

    2015-01-01

    Faseroptische Komponenten und Systeme sind heute unverzichtbar im Bereich der Datenübertragung, der Sensorik und Messtechnik, der Materialbearbeitung und in der Medizintechnik. Bei hohen Lichtleistungen in Glasfasern mit kleinen Querschnitten treten dabei nichtlineare optische Effekte auf, die in einigen Anwendungen gezielt genutzt werden können, aber in anderen Fällen störend sind. Aufbauend auf den Grundlagen der linearen Ausbreitung von Lichtwellen in Glasfasern werden in diesem Buch die nichtlinearen faseroptischen Effekte grundlegend und systematisch behandelt. Schwerpunkte sind dabei die Auswirkungen und Anwendungen der stimulierten Raman- und Brillouin-Streuung. Spezielle Aspekte der nichtlinearen Faseroptik werden am Beispiel der Raman-Faserlaser vertieft. Das Buch zeichnet sich durch fundierte theoretische Grundlagen, Angabe repräsentativer Zahlenwerte und anschauliche Beispiele aus. In kurzen Exkursen werden Zusammenhänge aufgezeigt und weiterführende Informationen gegeben. Zahlreiche Litera...

  4. Führung und Machiavellismus

    NARCIS (Netherlands)

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

    2015-01-01

    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

  5. Delegation und Kooperation im Gesundheitswesen

    OpenAIRE

    Rosenau, Henning

    2010-01-01

    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

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

    OpenAIRE

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

    2009-01-01

    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...

  7. Treatment for myeloid leukaemia of Down syndrome: population-based experience in the UK and results from the Medical Research Council AML 10 and AML 12 trials.

    Science.gov (United States)

    Rao, Anupama; Hills, Robert K; Stiller, Charles; Gibson, Brenda E; de Graaf, Siebold S N; Hann, Ian M; O'Marcaigh, Aengus; Wheatley, Keith; Webb, David K H

    2006-03-01

    Down syndrome (DS) children are at an increased risk of developing myelodysplasia and acute myeloid leukaemia (AML). We retrospectively analysed the population-based data on 81 children with myeloid leukaemia of Down syndrome (ML-DS) from the UK National Registry of Childhood Tumours and experience in the Medical Research Council (MRC) AML 10 and AML 12 trials, which enrolled 46 children with ML-DS from 1988 to 2002. Eight per cent of UK children with AML had DS, but DS children comprised only 5% of children registered in MRC trials. The unique clinical characteristics of ML-DS were confirmed. Overall survival (OS) of ML-DS at 5 years increased from 47% in UK children diagnosed from 1988 to 1995 to 75% in children diagnosed from 1996 to 2002. OS for DS children registered in AML 10 and AML 12 was 74% in 5 years and improved from AML 10 to AML 12 (56% vs. 83%) There was no significant difference in OS between DS and non-DS children (OS: 74% vs. 62%, P = 0.4) in the trials, but this result masked a significant increase in early death amongst DS children, with a significant reduction in mortality later on. Relapse was significantly reduced (3% vs. 39%, P = 0.0003), leading to the improved disease-free survival (83% vs. 56%, P = 0.02). Given the increased number of early treatment-related deaths, future treatment protocols should aim to reduce chemotherapy dosage or intensity whilst maintaining low rates of resistant and recurrent disease.

  8. [VALIDATION OF THE HUNGARIAN MDS-UPDRS: WHY DO WE NEED A NEW PARKINSON SCALE?].

    Science.gov (United States)

    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

    2014-03-30

    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'.

  9. 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.

    2014-01-01

    Acute myeloid leukemia (AML) is an aggressive and lethal blood cancer maintained by rare populations of leukemia stem cells (LSCs). Selective targeting of LSCs is a promising approach for treating AML and preventing relapse following chemotherapy, and developing such therapeutic modalities is a k...

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

    DEFF Research Database (Denmark)

    Madsen, Stine Skov; Krenk, Steen

    2017-01-01

    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 which...

  11. Beruf und Alltag alleinlebender Frauen

    Directory of Open Access Journals (Sweden)

    Ellen Seßar-Karpp

    2003-11-01

    Full Text Available Ein Leben ohne Partner und Kinder könnte zu einer Erweiterung des Selbst und damit zu einer positiven Persönlichkeitsveränderung führen. Dieser Hypothese geht U. Schlicht in Interviews mit 15 alleinlebenden Akademikerinnen in Berlin nach und findet ihre Hypothese weitgehend bestätigt.

  12. Der Bachelor in Sozial- und Erziehungswissenschaften (BSSE) und seine Praxisfelder

    OpenAIRE

    Böwen, Petra; Dujardin, Céline

    2017-01-01

    Der vorliegende Forschungsbericht „Der Bachelor in Sozial- und Erziehungswissenschaften (BSSE) und seine Praxisfelder“ beschäftigt sich mit dem Studiengang des BSSE und stellt seine Bedeutung für die luxemburgische Gesellschaft im Allgemeinen und für den Arbeitsmarkt der Sozialen Arbeit im Besonderen dar. Er zeigt die Vernetzung der vielfältigen Praxisfelder und der verschiedenen politischen Bereiche auf. Letztere werden durch Beiträge der jeweiligen Minister von den acht zuständigen Minis...

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

    OpenAIRE

    Lucas, Rainer

    2000-01-01

    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 ...

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

    Science.gov (United States)

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

    2006-04-21

    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.

  15. 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

    2006-01-01

    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

  16. The HPB-AML-I cell line possesses the properties of mesenchymal stem cells

    Directory of Open Access Journals (Sweden)

    Tatsumi Eiji

    2010-12-01

    Full Text Available Abstract Background In spite of its establishment from the peripheral blood of a case with acute myeloid leukemia (AML-M1, HPB-AML-I shows plastic adherence with spindle-like morphology. In addition, lipid droplets can be induced in HPB-AML-I cells by methylisobutylxanthine, hydrocortisone, and indomethacin. These findings suggest that HPB-AML-I is similar to mesenchymal stem cells (MSCs or mesenchymal stromal cells rather than to hematopoietic cells. Methods To examine this possibility, we characterized HPB-AML-I by performing cytochemical, cytogenetic, and phenotypic analyses, induction of differentiation toward mesenchymal lineage cells, and mixed lymphocyte culture analysis. Results HPB-AML-I proved to be negative for myeloperoxidase, while surface antigen analysis disclosed that it was positive for MSC-related antigens, such as CD29, CD44, CD55, CD59, and CD73, but not for CD14, CD19, CD34, CD45, CD90, CD105, CD117, and HLA-DR. Karyotypic analysis showed the presence of complicated abnormalities, but no reciprocal translocations typically detected in AML cases. Following the induction of differentiation toward adipocytes, chondrocytes, and osteocytes, HPB-AML-I cells showed, in conjunction with extracellular matrix formation, lipid accumulation, proteoglycan synthesis, and alkaline phosphatase expression. Mixed lymphocyte culture demonstrated that CD3+ T-cell proliferation was suppressed in the presence of HPB-AML-I cells. Conclusions We conclude that HPB-AML-I cells appear to be unique neoplastic cells, which may be derived from MSCs, but are not hematopoietic progenitor cells.

  17. Konservative und operative Therapie bei Harninkontinenz, Deszensus und Urogenitalbschwerden

    Directory of Open Access Journals (Sweden)

    Eberhard J

    2000-01-01

    Full Text Available Urogynäkologische Beschwerden wie Harninkontinenz, Infektionen, vulvo-vaginale und vesikale Reizzustände, Juckreiz, Dyspareunie, Beckenbodenschwäche, Deszensusbeschwerden werden in irgendeiner Form bei fast jeder Frau im Laufe ihres Lebens zur behandlungsbedürftigen Krankheit. Die Ursachen dieser häufigsten Frauenleiden sind vielfältig. Eine erfolgreiche Therapie sollte auf der Polyätiologie urogynäkologischer Krankheiten aufbauen und die verschiedenen Therapiemöglichkeiten zu einem patienten- und krankheitsadaptierten Behandlungskonzept zusammenfügen. Die Bausteine der konservativen Therapie sind: Trink- und Miktionstraining, Physiotherapie mit den Hilfsmitteln Kugeln, Kegel, Elektrostimulation und Biofeedbackmethoden; Östrogene, Pessare, Infekttherapie, Intimpflege, blasenrelaxierende und andere urogynäkologische Medikamente. Der Einsatz dieser Therapiebausteine wird ausführlich besprochen. Auch wird gezeigt, wann und wie operiert werden soll, wenn die konservative Therapie nicht zum Ziel führt.

  18. Patentierung und Patentlage

    Science.gov (United States)

    Herrmann, Uwe

    Gewerbliche Schutzrechte nehmen in der nationalen Rechts- und Wirtschaftsordnung sowie auch auf internationaler Ebene stetig an Bedeutung zu. Sie dienen dem Schutz geistigen Eigentums und sind für jeden Gewerbetreibenden nicht nur im Hinblick darauf von Bedeutung, eigene Rechte zu sichern, sondern auch insofern von Relevanz, dass ein Verstoß gegen Rechte Dritter zu vermeiden ist. Zu den gewerblichen Schutzrechten gehören unter anderem Kennzeichenrechte, Geschmacksmusterrechte sowie die sogenannten technischen Schutzrechte in Form des Patents sowie des Gebrauchsmusters. Die folgenden Ausführungen befassen sich ausschließlich mit den technischen Schutzrechten und geben eine kurze Einführung in die Voraussetzungen, das Entstehen und den Wegfall sowie in die Wirkungen technischer Schutzrechte. Beleuchtet wird die Situation im Wesentlichen im Hinblick auf nationale technische Schutzrechte, d. h. auf Deutsche Patente und Gebrauchsmuster sowie auf Europäische Patente, die Schutz in Deutschland entfalten. Die Möglichkeit der Erlangung von Schutzrechten im außereuropäischen Ausland wird nur am Rande gestreift.

  19. Supraleitung Grundlagen und Anwendungen

    CERN Document Server

    Buckel, Werner

    2013-01-01

    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...

  20. Rosetta und Yella

    Directory of Open Access Journals (Sweden)

    Urs Urban

    2009-11-01

    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.

  1. [Initial subretinal localization of acute myeloblastic leukemia (AML5) recurrence].

    Science.gov (United States)

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

    2001-10-13

    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.

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

    Science.gov (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

    2017-09-15

    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. Venture Kapital und Life Science

    Science.gov (United States)

    Moss, Sebastian; Beermann, Christian

    Um sich weiter im internationalen Wettbewerb behaupten zu können, müssen deutsche Unternehmen heute in Schlüsseltechnologien wie die Medizintechnik und die Biotechnologie, zusammenfassend unter dem Begriff der Life Sciences bekannt, investieren. Eine führende Wettbewerbsposition erfordert immer die konsequente Weiterentwicklung von Produkten und Lösungen, um Innovationspotenziale in medizinische Verfahren umzusetzen. Die damit unmittelbar verbundenen hohen Ausgaben für Forschung und Entwicklung stellen ein bedeutendes Problem junger Life Science Unternehmen dar. Vor allem die, verglichen mit nicht-medizinischen Branchen, längeren Forschungs- und Entwicklungszyklen in der Frühphase eines Life Science Unternehmens und die längere Dauer bis zur Profitabilität erhöhen das Risiko der Finanzinvestoren. Die Zeitdauer, um ein medizinisches Produkt bis zur Marktreife zu entwickeln und letztlich auf dem Markt anzubieten, kann aufgrund der notwendigen intensiven Forschung nur unscharf geplant werden und erhöht die Unsicherheit über den Zeitpunkt der ersten Einnahmen. Damit verschärfen sich gerade im Life Science Bereich allgemeine Problematiken von Gründungs- und Wachstumsfinanzierungen wie starke Informationsasymmetrien zwischen Gründer und potentiellen Kapitalgebern. Oftmals ist die Entwicklung einer innovativen Technologie abhängig von einzelnen Personen, von deren Wissen und Engagement die Umsetzung und der Erfolg eines gesamten Produktkonzeptes abhängen.

  4. Der Nahostkonflikt und die Medien

    Directory of Open Access Journals (Sweden)

    Carola Richter

    2014-06-01

    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.

  5. Digitalisierung und Selbstbestimmung

    Directory of Open Access Journals (Sweden)

    Eisenberger, Iris

    2017-12-01

    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.

  6. Wald und Forstwirtschaft

    Science.gov (United States)

    Köhl, Michael; Plugge, Daniel; Gutsch, Martin; Lasch-Born, Petra; Müller, Michael; Reyer, Christopher

    In der Vergangenheit haben sich Wälder an die geringen Veränderungen des am Wuchsort herrschenden Klimas angepasst. Die gegenwärtige Geschwindigkeit des Klimawandels in Verbindung mit der aktuellen Verteilung der Baumarten überfordert jedoch die natürliche Anpassung. Vegetationszonen, Verbreitungsgebiete der Baumarten und Artzusammensetzung der Wälder verschieben sich. Das Kapitel charakterisiert die Folgen, die der Klimawandel für die Wälder mit sich bringt, stellt Schadfaktoren im Einzelnen vor und schildert die Auswirkungen auf die Produktivität. Darüber hinaus wird detailliert auf die Rolle des Waldes als Kohlenstoffspeicher eingegangen, denn Wälder produzieren nicht nur den nachwachsenden Rohstoff Holz, sondern sie leisten auch viel für die Umwelt und wirken ausgleichend auf das Klima. Auch mögliche Anpassungsoptionen werden dargestellt.

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

    Directory of Open Access Journals (Sweden)

    Liveri Angeliki

    2010-01-01

    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.

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

    Science.gov (United States)

    Paasch, Uwe; Schwandt, Antje; Seeber, Nikolaus; Kautz, Gerd; Grunewald, Sonja; Haedersdal, Merete

    2017-05-01

    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 Optionen für den Dermatologen erschlossen werden konnten. Wurden bisher zum Beispiel mit fraktionalen Lasern Falten behandelt, sind eben diese Systeme heute in Kombination mit Medikamenten wichtige Werkzeuge bei der Behandlung von Narben, bei Feldkanzerisierung und epithelialen Tumoren. Die Anforderungen an den die Indikation stellenden und vorzugsweise therapierenden Arzt steigen mit der immer komplexer werdenden Technik und den zunehmenden Komorbiditäten und Komedikationen einer älter werdenden Patientenklientel. Parallel etabliert wurden, zunächst für einige wenige Indikationen, Geräte für die Heimanwendung, die sich durch geringe Leistung und spezielle Sicherheitsvorkehrungen zur Vermeidung von Unfällen, Risiken und Nebenwirkungen auszeichnen. Trotz der reduzierten Effizienz solcher Selbstbehandlungsmaßnahmen steigt die Wahrscheinlichkeit einer Fehlanwendung, da die Grundvoraussetzung für eine korrekte Therapie, nämlich die exakte Diagnose und Indikationsstellung, nicht vorausgesetzt werden kann. Bei einer Haarentfernung können so Pigmenttumoren, bei einer Faltentherapie neoplastische Hautveränderungen adressiert und zu erwartende, unvorhergesehene und neue Nebenwirkungen und Komplikationen induziert werden. In diesem Szenario ist es wichtig, alle potenziellen Anwender dieser neuen Technologien vor deren Einsatz so zu qualifizieren, dass den Therapierten maximale Therapiesicherheit bei höchster Effizienz unter dem Leitbild diagnosis certa - ullae therapiae fundamentum garantiert wird. © 2017 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd.

  9. 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: eva.szegezdi@nuigalway.ie [Apoptosis Research Center, National University of Ireland, University Road, Galway (Ireland); School of Natural Sciences, National University of Ireland, University Road, Galway (Ireland)

    2011-03-15

    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.

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

    Directory of Open Access Journals (Sweden)

    Eva Szegezdi

    2011-03-01

    Full Text Available 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.

  11. Nutzerorientiertes Management von materiellen und immateriellen Informationsobjekten

    OpenAIRE

    Hübsch, Chris

    2001-01-01

    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.

  12. Identification of novel genomic aberrations in AML-M5 in a level of array CGH.

    Directory of Open Access Journals (Sweden)

    Rui Zhang

    Full Text Available To assess the possible existence of unbalanced chromosomal abnormalities and delineate the characterization of copy number alterations (CNAs of acute myeloid leukemia-M5 (AML-M5, R-banding karyotype, oligonucelotide array CGH and FISH were performed in 24 patients with AML-M5. A total of 117 CNAs with size ranging from 0.004 to 146.263 Mb was recognized in 12 of 24 cases, involving all chromosomes other than chromosome 1, 4, X and Y. Cryptic CNAs with size less than 5 Mb accounted for 59.8% of all the CNAs. 12 recurrent chromosomal alterations were mapped. Seven out of them were described in the previous AML studies and five were new candidate AML-M5 associated CNAs, including gains of 3q26.2-qter and 13q31.3 as well as losses of 2q24.2, 8p12 and 14q32. Amplication of 3q26.2-qter was the sole large recurrent chromosomal anomaly and the pathogenic mechanism in AML-M5 was possibly different from the classical recurrent 3q21q26 abnormality in AML. As a tumor suppressor gene, FOXN3, was singled out from the small recurrent CNA of 14q32, however, it is proved that deletion of FOXN3 is a common marker of myeloid leukemia rather than a specific marker for AML-M5 subtype. Moreover, the concurrent amplication of MLL and deletion of CDKN2A were noted and it might be associated with AML-M5. The number of CNA did not show a significant association with clinico-biological parameters and CR number of the 22 patients received chemotherapy. This study provided the evidence that array CGH served as a complementary platform for routine cytogenetic analysis to identify those cryptic alterations in the patients with AML-M5. As a subtype of AML, AML-M5 carries both common recurrent CNAs and unique CNAs, which may harbor novel oncogenes or tumor suppressor genes. Clarifying the role of these genes will contribute to the understanding of leukemogenic network of AML-M5.

  13. Angiomyolipoma (AML) without visible fat: Ultrasound, CT and MR imaging features with pathological correlation

    Energy Technology Data Exchange (ETDEWEB)

    Hakim, Shaheed W.; Flood, Trevor A. [The Ottawa Hospital, University of Ottawa, Department of Anatomical Pathology, Ottawa, Ontario (Canada); Schieda, Nicola; Hodgdon, Taryn; McInnes, Matthew D.F.; Dilauro, Marc [The Ottawa Hospital, University of Ottawa, Department of Medical Imaging, Ottawa, Ontario (Canada)

    2016-02-15

    To compare imaging findings with histopathology in AML without visible fat (AML{sub wvf}). With IRB approval, we identified 18 AML{sub wvf} that underwent CT between 2002-2014. A radiologist measured NECT-attenuation, corticomedullary (CM) and nephrographic (NG) enhancement, echogenicity relative to renal cortex (RC) (N = 5), T2W (T2{sub AML}/T2{sub RC}) signal-intensity (SI), and chemical-shift SI ([SI{sub IN-PHASE} - SI{sub OPPOSED-PHASE}]/SI{sub IN-PHASE}) indices (N = 6). A pathologist re-evaluated 15/18 AML{sub wvf} for 1) < or > 25 % adipocytes/high-power-field (HPF), 2) ''many or few'' blood vessels. Comparisons were performed using chi-square and independent t-tests. 73.3 %(11/15) of AML{sub wvf} had <25 % adipocytes/HPF and 86.7 %(13/15) had ''many'' blood vessels. NECT-attenuation was 41.8(±6.9) HU. 61.1 %(11/18) of AML{sub wvf} were hyper-attenuating and 38.9 %(7/18) iso-attenuating; attenuation was associated with %-adipocytes/HPF, (p = 0.01). CM/NG enhancement were 63.3(±20.8)/51.7(±15.5) HU. 72.2 %(13/18) of AML{sub wvf} had wash-out enhancement, with no association with amount of blood vessels at pathology, (p = 0.68). No difference in echogenicity was noted by histology (p > 0.05). All AML{sub wvf} were T2-hypointense (SI ratio = 0.61 [±0.1]). 2/6 AML{sub wvf} showed SI drop on chemical-shift MRI; both were iso-attenuating and were associated with >25 % adipocytes/HPF (p = 0.04). AML{sub wvf} are typically T2-hypointense and hyper-attenuating with wash-out enhancement due to abundant smooth muscle and vessels respectively. Iso-attenuating AML{sub wvf} with microscopic fat on MRI contain more adipocytes/HPF. (orig.)

  14. The NPM1 mutation type has no impact on survival in cytogenetically normal AML.

    Directory of Open Access Journals (Sweden)

    Friederike Pastore

    Full Text Available NPM1 mutations represent frequent genetic alterations in patients with acute myeloid leukemia (AML associated with a favorable prognosis. Different types of NPM1 mutations have been described. The purpose of our study was to evaluate the relevance of different NPM1 mutation types with regard to clinical outcome. Our analyses were based on 349 NPM1-mutated AML patients treated in the AMLCG99 trial. Complete remission rates, overall survival and relapse-free survival were not significantly different between patients with NPM1 type A or rare type mutations. The NPM1 mutation type does not seem to play a role in risk stratification of cytogenetically normal AML.

  15. Increased HDAC1 deposition at hematopoietic promoters in AML and its association with patient survival

    DEFF Research Database (Denmark)

    Tickenbrock, Lara; Klein, Hans-Ulrich; Trento, Cristina

    2011-01-01

    was established, that revealed an AML specific pattern of HDAC1 distribution. Many of the HDAC1-binding altered promoters regulate genes involved in hematopoiesis, transcriptional regulation and signal transduction. HDAC1 binding patterns were associated with patients' event free survival. This is the first study...... to determine HDAC1 modification patterns in a large number of AML and ALL specimens. Our findings suggest that dyslocalization of HDAC1 is a common feature in AML. Importantly, HDAC1 modifications possess prognostic power for patient survival. Our findings suggest that altered HDAC1 localization...

  16. Editorial: Medien und soziokulturelle Unterschiede

    Directory of Open Access Journals (Sweden)

    Horst Niesyto

    2009-09-01

    Full Text Available Kinder, Jugendliche und Erwachsene nutzen Medien in sehr unterschiedlicher Weise. Insbesondere handlungstheoretische Ansätze der Medienforschung konnten überzeugend belegen, dass Menschen keine passive Zielscheibe von Medien sind, sondern diese aktiv nutzen. Medienrezeption und Medienaneignung wird als Teil sozialen Handelns verstanden, die Mediennutzung wird im Lebenskontext der Menschen verortet, es wird nach der Bedeutung der Medien im Alltag und für die Lebensbewältigung gefragt. Kulturtheoretisch motivierte Studien, die die Eigenleistungen der Individuen im Auswahlprozess und in der Konstruktion von Bedeutungen betonen, verdeutlichten eigensinnige Prozesse der Medienaneignung und eine Vielfalt medienkultureller Orientierungen. Im Bereich des Lernens mit Medien wurden die Chancen selbstgesteuerter Lernprozesse mit digitalen Medien in verschiedenen Forschungsprojekten herausgearbeitet. Ein kritischer Blick auf die Medienentwicklung und die Mediennutzung kann nicht verleugnen, dass es soziokulturelle Unterschiede und Formen sozialer Ungleichheit in der Mediennutzung gibt. In den letzten Jahren entstanden in diesem Zusammenhang vermehrt Studien zu Themenbereichen wie ‹Digital divide›, Zunahme medialer Wissens- und Bildungsklüfte, Bildungsbenachteiligung und Medienaneignung. Verschiedene Fachtagungen griffen die Thematik auf, z.B. der vom JFF Institut für Medienpädagogik in Forschung und Praxis und der Pädagogischen Hochschule Ludwigsburg/Abteilung Medienpädagogik veranstaltete Fachkongress «Soziale Ungleichheit – Medienpädagogik – Partizipation» am 17./18.10.2008 in Bonn und das von der Gesellschaft für Medienpädagogik und Kommunikationskultur e.V. (GMK veranstaltete Forum «Geteilter Bildschirm – Getrennte Welten?» am 21.–23.11.2008 in Rostock. In diesen Studien und Fachtagungen ging es darum herauszuarbeiten, worin soziokulturelle Unterschiede in der Medienaneignung bestehen, was die Gründe hierfür sind, wie diese

  17. Substanzbegriff und systematik

    NARCIS (Netherlands)

    Lütjeharms, W.J.

    1934-01-01

    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

  18. Sport und Marken

    OpenAIRE

    Nufer, Gerd

    2018-01-01

    Fußballspieler sind heutzutage viel mehr als nur Fußballer. Weltstars wie Cristiano Ronaldo, Neymar oder früher David Beckham und schon Pelé haben ihre Namen als Marken etabliert. Es gibt jedoch auch Negativbeispiele, bei denen trotz anfänglicher sportlicher Erfolge der Schuss eher nach hinten losging.

  19. Rational und Fair

    NARCIS (Netherlands)

    Ockenfels, A.; Raub, W.

    2010-01-01

    Zusammenfassung: Das „Standardmodell“ des Rational Choices-Ansatzes, das Modell des homo oeconomicus, unterstellt rationales und eigennütziges Verhalten. Das Standardmodell hat manche Vorzüge, aber es gibt auch empirische Regelmäßigkeiten, die diesem Modell widersprechen. Wir behandeln

  20. Wissensmanagement und Medienbildung

    Directory of Open Access Journals (Sweden)

    Gerhard Scheidl

    2012-09-01

    Full Text Available Die Querschnittsthematik "Medienbildung" stößt auf eine immer noch fachzentrierte Ausbildung und Schulpraxis. Mögliche Lösungen könnten Überlegungen aus dem Wissensmanagement bieten, wie Gerhard Scheidl in seinem Beitrag auf verschiedenen Ebenen erläutert.

  1. HEMATOPOIETIC CELL TRANSPLANTATION FOR OLDER PATIENTS WITH MDS

    Directory of Open Access Journals (Sweden)

    Mazyar Shadman

    2014-09-01

    Full Text Available The incidence of myeloid malignancies, including myelodysplastic syndromes (MDS increases with age. While several therapeutic modalities have been developed, for most of these patients the only treatment with curative potential is allogeneic hematopoietic cell transplantation (HCT. The development of reduced/low intensity transplant conditioning regimens allows to successfully transplant patients in their ‘60s and even ‘70s, although comorbidities may determine who does come to transplantation and who does not. Also, as many as half of the patients will develop graft versus host disease (GVHD, even with HLA matched  donors, requiring therapy for extended periods of time,  and GVHD and treatment  with glucocorticoids is likely to impact the quality  of life. Nevertheless, dependent upon disease stage at HCT, the presence of comorbidities and the regimen used, 30% to 50% of patients  60 years of age or older, may survive long-term cured of their disease. Future studies should focus on the incorporation of non-transplant modalities into the overall transplant approach, the prevention of GVHD, and the utilization of immunotherapy to reduce the incidence of relapse and GVHD and further improve overall transplant success.

  2. MDS-Multifunctional Dynamometer for Application in Space

    Science.gov (United States)

    Adamcik, G.; Barta, N.; Talla, R.; Angeli, T.; Kozlovskaya, I. B.; Grigoriev, A. I.; Tschan, H.; Bachl, N.

    2008-06-01

    The project MDS (Multifunctional Dynamometer for Application in Space) is an international collaboration of the University of Vienna (Faculty of Sport Science, Department of Sport and Exercise Physiology), the Russian Academy of Sciences (Institute of Biomedical Problems) and the Technical University of Vienna (Institute for Engineering Design and Logistics Engineering) with the aim to develop a training and diagnostic device that counteracts the muscle and bone loss during long term space flights. Due to the scientific results of the last years research in space medicine, it is well known, that the muscles and bones of the lower extremities and the trunk are most affected by the atrophy. Based on this knowledge a various number of resistance exercises can be done in order to train the muscles of these parts of the body and to increase the efficiency of the training by intra- and intermuscular coordination. The resisting power for the training is provided by an electric motor, thereby force, position and speed of the training can be well-regulated for different training modes.

  3. MDS 3.0 for Nursing Homes and Swing Bed Providers

    Data.gov (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...

  4. Magnetic Decreases (MDs and mirror modes: two different plasma β changing mechanisms

    Directory of Open Access Journals (Sweden)

    E. Echer

    2010-09-01

    Full Text Available We discuss two different physical processes that create localized high β plasma regions. One is nonlinear wave-steepening, generating magnetic decreases (MDs by a ponderomotive force. The other is the mirror instability generating alternating high and low β plasma regions. It is demonstrated that MDs and mirror modes are observationally quite different structures. MDs spatially occur in interplanetary space and mirror modes primarily in planetary magnetosheaths. MDs are characterized by: 1 variable (exponentially decreasing number with increasing angular changes, 2 variable (exponentially decreasing thicknesses, and 3 no characteristic inter-event spacings. In sharp contrast, mirror modes are characterized by: 1 little or no angular changes across the structures, 2 a characteristic scale size, and 3 are quasiperiodic in nature. Arguments are presented for the recently observed magnetic dips in the heliosheath being mirror mode structures. The sources of free energy for instability are discussed. Both structures are important for energetic particle transport in astrophysical and heliospheric plasmas.

  5. 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).

    Science.gov (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

    2016-12-01

    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.

  6. A.S. Neill und Summerhill : Eine Rezeptions- und Wirkungsanalyse

    OpenAIRE

    Kühn, Axel D.

    2002-01-01

    Die Arbeit beschäftigt sich mit dem Einfluß Alexander Neills und seiner Schule Summerhill im Spiegel sowohl der deutschen als auch der internationalen Rezeption. In ersten Teil 'Literarisches' wird Neills Leben mit Fokus auf sein öffentliches Wirken beschrieben. Alle seine Bücher und die meisten seiner Artikel werden analysiert und der sie begleitenden öffentlichen Diskussion gegenübergestellt. Der zweite Teil, 'Profanes' beschäftigt sich mit der Diskussion...

  7. Darstellung hochmolekularer und verzweigter Polyisobutene durch Einsatz von Makroinitiatoren, cyclischen Dienen und Initiatormonomeren

    OpenAIRE

    Schäfer, Marcus

    2007-01-01

    Die Synthese und Charakterisierung von hochmolekularen und verzweigten Polyisobutenen durch Einsatz von neuartigen Makroinitiatoren, cyclischen Dienen und Initiatormonomeren stand im Mittelpunkt dieser Arbeit. Es wurden Lösungsansätze zu aktuellen wissenschaftlichen und technischen Problemen aufgezeigt und miteinander verglichen. Die Kombination von DPE-Technik und kationischer Polymerisation führte zu neuartigen Graftcopolymeren mit variablem Rückgrat und Polyisobutenseitenästen. Die Kombina...

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

    Science.gov (United States)

    Raju, C.; Vidya, R.

    2016-06-01

    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.

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

    Directory of Open Access Journals (Sweden)

    Mayela Rodríguez-Violante

    2014-01-01

    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.

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

    Science.gov (United States)

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

    2018-04-01

    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.

  11. Herausforderungen kleiner und mittlerer Unternehmen

    Science.gov (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.

  12. Ödipus und Popkultur

    Directory of Open Access Journals (Sweden)

    Andrea Schüler

    2003-03-01

    Full Text Available Marjorie Garber inspiziert in ihrer ebenso eloquenten wie materialreichen Abhandlung die abendländische Geistes- und Kulturgeschichte von der Antike bis zur Postmoderne und kommt zu dem Ergebnis, dass Bisexualität allgegenwärtig und zugleich kulturell und politisch unsichtbar ist. Die zahlreichen Beispiele bisexuellen Begehrens, die sich sowohl unter literarischen Figuren als auch bei bekannten historischen Personen finden lassen, seien von ihren Interpret/-innen stets der Dichotomie Homo- oder Heterosexualität unterworfen worden. Erfahrungen, die dieser binären Opposition widersprechen, würden als „Phase“, „Experiment“, „Verirrung“, „Selbstbetrug“ usw. abgewertet. Im Sinne postmoderner Identitätskritik plädiert die Autorin für eine Befreiung der Erotik von solchen Normierungen und preist das subversive und transgressive Potential menschlicher Sexualität jenseits der Kategorien homo- hetero- oder bisexuell.

  13. Wissenschaft zwischen Lebensform und Karrierejob

    OpenAIRE

    Rogge, Jan-Christoph

    2017-01-01

    Die These, die in der Dissertation entfaltet wird, lautet, dass mit dem wissenschaftlichen Beruf heute widersprüchliche Karriereanforderungen verbunden sind: Die traditionellen Sozial- und Organisationsideen der Wissenschaft sind noch immer wirkmächtig. Die Wissenschaft soll nach wie vor Lebensform und Berufung sein. Zugleich ist die Wissenschaft aber von einem Transformationsprozess erfasst, der den wissenschaftlichen Arbeitsmarkt zu einem „Winner-take-all“-Markt und die Wissenschaft zu eine...

  14. Gemtuzumab Ozogamicin as Post-Consolidation Therapy Does Not Prevent Relapse In Children with AML. Results of the NOPHO-AML 2004 Study

    DEFF Research Database (Denmark)

    Hasle, Henrik; Abrahamsson, Jonas; Forestier, Erik

    There are no data on the role of post-consolidation therapy with gemtuzumab ozogamicin, (GO, Mylotarg) in children with AML. The NOPHO-AML 2004 protocol included two induction courses and four consolidation courses followed by a post-consolidation randomization to GO or no further therapy (Clinical....... No significant decrease in hemoglobin was observed whereas severe neutropenia occurred in 96% of the patients. Recovery to neutrophils > 0.5 lasted a median of 15 days. Febrile neutropenia followed 39% of the GO courses but none were life-threatening. A moderate decline in platelet count was noted with platelets...

  15. 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

    2018-01-01

    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 13....... The t(7;12) was only present in patients trisomy 19 (literature: 86%, NOPHO: 100%) and +8 (literature: 19%, NOPHO: 14%). Seventeen...... patients was treated with hematopoietic stem cell transplantation (HSCT) in first complete remission. Relapse was frequent but the salvage rate using HSCT was high. We conclude that t(7;12)(q36;13) is a unique subgroup of childhood AML with presentation before 2 years of age with most cases being...

  16. Jugendhilfe und Schule. Konzepte und Grundpositionen - historische und internationale Aspekte der Bezüge von Jugendhilfe und Schule

    OpenAIRE

    Schreck Graf von Reischach, Gerald

    2006-01-01

    Es gibt mittlerweile vielfältige Bezüge von Jugendhilfe und Schule in Deutschland. Neben „Schulsozialarbeit“, die erstmals in der sechziger Jahren mit der Schulreform an Gesamtschulen installiert wurde, gibt es heute viele weitere Kooperationsformen zwischen Jugendhilfe und Schule. Da die Bezüge zwischen Jugendhilfe und Schule in Deutschland nach wie vor in hohem Maße klärungs- und entwicklungsbedürftig sind, will die vorliegende Arbeit dazu beitragen, sie im historischen, aktuell-konzepti...

  17. Extramedullary Acute Myeloid Leukemia (AML: Leukemic Pleural Effusion, Case Report and Review of the Literature

    Directory of Open Access Journals (Sweden)

    Naveen ePemmaraju

    2014-06-01

    Full Text Available Objective and Importance: Malignant pleural effusions occur in the setting of both solid and hematologic malignancies. Pleural effusion caused by leukemic infiltration is an unusual extramedullary manifestation of acute myeloid leukemia (AML with fewer than 20 cases reported.1-11 We report a case of pericardial and pleural effusions in a patient with AML and review the literature. Clinical presentation: In this case, a 55 year old man with previous history of myeloproliferative neoplasm (MPN experienced transformation AML, heralded by appearance of leukemic pleural effusions. The patient was identified to have leukemic pleural effusion based upon extended cytogenetic analysis of the pleural fluid, as morphologic analysis alone was insufficient. Intervention: The patient was treated with hypomethylator-based and intensive chemotherapy strategies, both of which maintained resolution of the effusions in the remission setting. Conclusion: Due to the rarity of diagnosis of leukemic pleural effusions, both cytogenetic and fluorescence in situ hybridization (FISH testing are recommended. Futhermore, systemic chemotherapy directed at the AML can lead to complete resolution of leukemic pleural effusions. Objective and ImportancePleural effusion caused by leukemic infiltration is an unusual extramedullary manifestation of acute myeloid leukemia (AML, but may be more common than previously thought. Fewer than 20 cases have been reported.1-11 We report a case of pericardial and pleural effusions in a patient with AML and review the literature.

  18. [Inhibitory Effect of Decitabine on Proliferation of MDS-L Cells and Its Mechanism].

    Science.gov (United States)

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

    2017-10-01

    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).

  19. [Establishment of Primary Adult MDS Nested Case-Control Study Cohort and Study of Risk Factors Associated with MDS Evolution to Leukemia].

    Science.gov (United States)

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

    2015-12-01

    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

  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

    2007-01-01

    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. 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.

  2. und Fremdsprachen im Prozess der Alphabetisierung und der ...

    African Journals Online (AJOL)

    Gemüseanbau, Fischfang und Viehzucht gehört. Die Landwirte, die von ihren täglichen. Tätigkeiten leben wollen, sind meist Analphabeten und können daher über ihre Projekte weder in der eigenen noch in der Fremdsprache schreiben. Deshalb werden in allen Regionen. Burkinas Alphabetisierungszentren gegründet ...

  3. Hegel und Gorgias

    DEFF Research Database (Denmark)

    Huggler, Jørgen

    Hegel und Gorgias /Jørgen Huggler (University of Aarhus, Denmark) (huggler(at)dpu.dk) 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...

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

    Science.gov (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

    2017-09-28

    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 clinicaltrials.gov (identifier NCT01720225). © 2017 by The American Society of Hematology.

  5. MDS-associated somatic mutations and clonal hematopoiesis are common in idiopathic cytopenias of undetermined significance.

    Science.gov (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

    2015-11-19

    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.

  6. SETBP1 mutations drive leukemic transformation in ASXL1-mutated MDS.

    Science.gov (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

    2015-04-01

    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.

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

    Science.gov (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

    2015-09-21

    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.

  8. Osteoporosetherapie und Frakturheilung

    Directory of Open Access Journals (Sweden)

    Gruber R

    2010-01-01

    Full Text Available Ziel der Übersichtsarbeit ist es, die möglichen Auswirkungen der pharmakologischen Osteoporosetherapie auf die Frakturheilung zu beschreiben. Die Motivation, dieses Thema aufzugreifen, begründet sich (1 darin, dass Osteoporose als Risikofaktor für eine verzögerte Knochenregeneration angesehen wird und (2 dass jene Zellen, die an der Frakturheilung beteiligt sind, auch potenzielle Zielzellen einer pharmakologischen Osteoporosetherapie sind. Die Reduktion des Frakturrisikos durch Bisphosphonate, Parathormon, selektive Estrogenrezeptormodulatoren (SERMs und Strontiumranelat ist gut dokumentiert und basiert auf einer Verschiebung des Remodelings, also des Knochenumbaugleichgewichts. Frakturen treten im geringeren Ausmaß auch während dieser Behandlung auf. Kontrollierte klinische Studien, die den Einfluss der pharmakologischen Osteoporosetherapie auf die Frakturheilung untersuchen, liegen jedoch nicht vor. Hingegen gibt es zahlreiche präklinische Studien, die darauf hindeuten, dass sowohl Bisphosphonate als auch Peptide der PTH-Familie die Frakturheilung beeinflussen können. Schlussfolgerungen über deren klinische Relevanz können unter der Prämisse, dass präklinische Experimente nur bedingt die Situation im Menschen widerspiegeln, derzeit nicht angestellt werden. In den präklinischen Studien liegt zudem die Dosis der verabreichten Bisphosphonate und Peptide der PTH-Familie über jener der Osteoporosetherapie. Hinzu kommt, dass Risikofaktoren der Frakturheilung, wie metabolische Erkrankungen, die Behandlung mit Glukokortikoiden sowie fortgeschrittenes Alter in den präklinischen Studien zumeist unberücksichtigt bleiben. Klinische Studien sind demnach notwendig, um zu klären, ob eine pharmakologische Osteoporosetherapie nicht nur das Frakturrisiko reduziert, sondern auch die Frakturheilung beeinflusst.

  9. Genossenschaften und Franchising

    OpenAIRE

    Bonus, Holger; Wessels, Andrea Maria

    1998-01-01

    Die Neue Institutionenökonomik unterscheidet zwischen generellem (d.h. leicht weiterzugebendem) und spezifischem (d.h. schwer übertragbarem) Wissen. Die Industriewirtschaft beruhte weitgehend auf generellem Wissen. Die Unternehmensspitze hatte die beste Übersicht, was zu tiefgestaffelten Unternehmenshierarchien führte. Demgegenüber basiert die postindustrielle Wirtschaft in hohem Maße auf spezifischem Wissen. Insoweit hat die Basis den besseren Durchblick, weshalb ihr erhebliche Entscheidungs...

  10. Treatment for myeloid leukaemia of Down syndrome: population-based experience in the UK and results from the Medical Research Council AML 10 and AML 12 trials.

    NARCIS (Netherlands)

    Rao, A.; Hills, R.K.; Stiller, C.; Gibson, B.E.; Graaf, S.S.N. de; Hann, I.M.; O'Marcaigh, A.; Wheatley, K.; Webb, D.K.

    2006-01-01

    Down syndrome (DS) children are at an increased risk of developing myelodysplasia and acute myeloid leukaemia (AML). We retrospectively analysed the population-based data on 81 children with myeloid leukaemia of Down syndrome (ML-DS) from the UK National Registry of Childhood Tumours and experience

  11. Ethik und Sicherheitstechnik. Eine Handreichung

    NARCIS (Netherlands)

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

    2013-01-01

    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

  12. Identification of transcription factor AML-1 binding site upstream of human cytomegalovirus UL111A gene.

    Directory of Open Access Journals (Sweden)

    Xiaoqun Zheng

    Full Text Available Human cytomegalovirus (HCMV interleukin-10 (hcmvIL-10, encoded by HCMV UL111A gene, is a homolog of human IL-10. It exerts immunomodulatory effects that allow HCMV to evade host defense mechanisms. However, the exact mechanism underlying the regulation of hcmvIL-10 expression is not well understood. The transcription factor acute myeloid leukemia 1 (AML-1 plays an important role in the regulation of various genes involved in the differentiation of hematopoietic lineages. A putative AML-1 binding site is present within the upstream regulatory region (URR of UL111A gene. To provide evidence that AML-1 is involved in regulating UL111A gene expression, we examined the interaction of AML-1 with the URR of UL111A in HCMV-infected human monocytic THP-1 cells using a chromatin immunoprecipitation assay. HcmvIL-10 transcription was detected in differentiated THP-1 cells, but not in undifferentiated ones. Furthermore, the URR of UL111A showed a higher intensity of AML-1 binding, a higher level of histone H3 acetyl-K9, but a lower level of histone H3 dimethyl-K9 in differentiated THP-1 cells than undifferentiated cells. Down-regulation of AML1 by RNA interference decreased the expression of the UL111A gene. Our results suggest that AML-1 may contribute to the epigenetic regulation of UL111A gene via histone modification in HCMV-infected differentiated THP-1 cells. This finding could be useful for the development of new anti-viral therapies.

  13. Geographic Heterogeneity of the AML1-ETO Fusion Gene in Iranian Patients with Acute Myeloid Leukemia

    Directory of Open Access Journals (Sweden)

    Saeedeh Ghazaey Zidanloo

    2014-10-01

    Full Text Available Background: The human AML1 gene, located on chromosome 21, can be fused to the AML1- eight-twenty-one (ETO oncoprotein on chromosome eight, resulting in a t(8;21(q22;q22 translocation. Acute myeloid leukemia (AML associated with this translocation is considered a distinct AML with a favorable prognosis. Due to the various incidences of the translocation, which is associated with geographic diversities, investigation of molecular epidemiology is important to increase the awareness of physicians and hematologists regarding the frequency this chromosomal aberration. Methods: The patients were classified according to the French–American–British classification into eight groups: M0–M7. Determination of the prevalence of the AML1-ETO fusion gene was accomplished by TaqMan real-time PCR. Bone marrow samples from 113 patients with newly-diagnosed, untreated AML -M1, -M2, and -M4, and 20 healthy controls admitted to the Ghaem Hospital in Mashhad, Iran were studied. Results: The AML1-ETO fusion gene was detected up 50% of the M2 subgroup and absent in the M1 and M4 subtypes and healthy controls. Comparison of the prevalence of the t(8;21 translocation with results of previous studies showed that it varies between countries. This result may be due to geographic or ethnic differences, or both. Conclusions: The relatively high prevalence of the t(8;21 translocation in Iran was similar to that found in other Asian countries. It was closely associated with female gender, relatively young age, and FAB-M2 subtype. Its distribution varied considerably with geographic area. Therefore, further studies are needed to provide epidemiological data important for the establishment of optimal therapeutic strategies applicable to patients of each region.

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

    Index Scriptorium Estoniae

    Uibopuu, Henn-Jüri, 1929-2012

    1983-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Peter Kuon

    2016-03-01

    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.

  16. Bildanalyse in Medizin und Biologie

    Science.gov (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.

  17. Síndrome mielodisplásica secundária à quimio ou radioterapia: SMD relacionada a tratamento Myelodysplastic syndrome secondary to chemo: and radiotherapy MDS related to the treatment

    Directory of Open Access Journals (Sweden)

    Ronald F. Pinheiro

    2006-09-01

    Full Text Available O efeito leucemogênico dos agentes quimioterápicos após o tratamento para neoplasias é bem conhecido. Síndrome mielodisplásica secundária a quimio ou radioterapia, também denominada relacionada à terapia (SMD-t, geralmente ocorre quatro a sete anos após a exposição inicial ao agente quimio ou radioterápico, acomete habitualmente pacientes jovens, apresenta alta incidência de transformação para leucemia mielóide aguda (LMA, está associada a citopenias severas, displasia das três linhagens, celularidade medular reduzida e fibrose, e anormalidades citogenéticas em até 80% dos casos. As anormalidades mais freqüentes envolvem os cromossomos 5 e 7. No tocante à quimioterapia, os agentes alquilantes são as drogas mais comumente associadas com SMD-t. Quimioterápicos em altas doses usados como parte de regimes de condicionamento para transplantes de medula óssea e radioterapia, além dos esquemas COPP/ABV e BEACOPP, estão associados com SMD-t. Recentemente, drogas como azatioprina, cladribina e rituximab também foram relacionadas à SMD-t. Devido ao aumento da sobrevida de pacientes acometidos por neoplasias malignas, a SMD-t surge como efeito mutagênico desses tratamentos e confere prognóstico desfavorável.The leukaemogenic effect of chemotherapeutic agents after treatment for other malignancies have been well described. Myelodysplastic syndrome secondary to chemo- and radiotherapy (MDS-t usually develops four to seven years after the initial exposure to chemotherapy frequently involving young patients, shows a high incidence of transformation to AML, is associated with severe cytopenias, trilineage dysplasia, reduced marrow cellularity and fibrosis, and presents an incidence of chromosomal abnormalities of up to 80% of the cases. The most common abnormalities are related to chromosomes 5 and 7. Alkylating agents have been considered the most common drugs associated with MDS-t. High dose chemotherapy used as part of the

  18. [Clinical significance of WHO classification and MDS 2000 classification in myelodysplastic syndromes].

    Science.gov (United States)

    Akiba, M; Matsuda, A; Misumi, M; Yagasaki, F; Bessho, M

    2001-12-01

    Excluding chronic myelomonocytic leukemia, a total of 92 consecutive patients with myelodysplastic syndrome showing less than 20% blasts in the bone marrow were analyzed. We evaluated the clinical significance of the WHO and MDS 2000 classifications by reviewing each MDS patient according to the classification. The WHO criteria classified the MDS patients into 36 with RA, 22 with RCMD and 33 with RAEB, whereas according to the MDS 2000 criteria there were 19 RAEB-I patients and 15 RAEB-II patients. Based on the WHO classification, the RCMD patients had higher platelet counts and percentages of blasts among BM cells than the RA patients (P = 0.0018, P = 0.0001). Twenty percent of the RA patients, 44.8% of the RCMD patients, and 70.8% of the RAEB patients had cytogenetic abnormalities. Among them, the poor karyotype was present in 6.7% of the RA patients, 21.0% of the RCMD patients and 41.6% of the RAEB patients. The rate of acute leukemia death was 14.3% in the RA patients, 67.7% in the RAEB patients and 50.0% in the RCMD patients. Analysis of survival times revealed significant differences between RA and RCMD patients (P = 0.0482). The clinical features of RCMD patients were intermediate between those of RAEB and RA patients. There was no difference between the clinical features of the RAEB-I and RAEB-II patients in the MDS 2000 classification.

  19. MDS-UPDRS to assess non-motor symptoms after STN DBS for Parkinson's disease.

    Science.gov (United States)

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

    2016-01-01

    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.

  20. Incorporating novel approaches in the management of MDS beyond conventional hypomethylating agents.

    Science.gov (United States)

    Odenike, Olatoyosi

    2017-12-08

    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.

  1. [TOPICS-MDS: a versatile resource for generating scientific and social knowledge for elderly care].

    Science.gov (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

    2015-04-01

    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.

  2. Mutational profiling in patients with MDS: ready for every-day use in the clinic?

    Science.gov (United States)

    Bacher, Ulrike; Kohlmann, Alexander; Haferlach, Torsten

    2015-03-01

    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.

  3. Taufe und soziale/politische Inklusion und Exklusion in Byzanz

    Directory of Open Access Journals (Sweden)

    Wolfram Brandes

    2013-01-01

    Full Text Available Im Zentrum des Artikels steht nicht die konkrete Entwicklung des Sakraments der Taufe. Dies ist Gegenstand der Liturgiewissenschaft. Vielmehr werden bestimmte Aspekte der politischen bzw. kirchengeschichtlichen Entwicklung und ihre Regulierung durch Normen des weltlichen wie kanonischen Rechts betrachtet. Besondere Beachtung wurde der Problematik der Zwangstaufe, besonders von sog. Heiden und Juden, geschenkt. Deutlich wird z. B. im Falle der Unterdrückung von Heiden (bis zum Ende des 6. Jahrhunderts, dass hier soziale und politische Konflikte den eigentlichen Hintergrund darstellten. Die umstürzenden Wandlungen des byzantinischen Staates und der Staatskirche seit dem 7. Jahrhundert durch den expandierenden Islam und die Einwanderung slawischer Stämme ins byzantinische Kernland auf dem europäischen Kontinent (bes. Griechenland sowie die Notwendigkeit ebenfalls einsickernder Armenier in geregelten Formen zu integrieren, führte zu festgelegten Regelungen (sog. Aufnahme- bzw. Abschwörungsformeln, die in differenzierter Form die zum orthodoxen Christentum zu Bekehrenden – letztlich abgeschlossen durch die Taufe – behandelte. Weiterhin wird die Problematik der byzantinischen Mission im Inneren (Binnenmission wie als Mittel der Außenpolitik thematisiert. Die erfolgreiche Missionierung der Bulgaren und der Kiever Rus’ (»Taufe« Russlands im 9. und 10. Jahrhundert stellte einen bis heute wirkmächtigen Erfolg der byzantinischen Kirche bzw. des von dieser nicht zu trennenden byzantinischen Staates dar.

  4. [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-

    2012-01-01

    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.

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

    Science.gov (United States)

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

    2014-04-01

    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.

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

    Science.gov (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

    2012-01-01

    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.

  7. 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.

  8. Parkinson's disease severity levels and MDS-Unified Parkinson's Disease Rating Scale.

    Science.gov (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

    2015-01-01

    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.

  9. SF3B1-initiating mutations in MDS-RSs target lymphomyeloid hematopoietic stem cells.

    Science.gov (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

    2017-08-17

    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.

  10. Time-dependent changes in mortality and transformation risk in MDS.

    Science.gov (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

    2016-08-18

    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.

  11. Prognostic classification of MDS is improved by the inclusion of FISH panel testing with conventional cytogenetics.

    Science.gov (United States)

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

    2017-10-01

    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.

  12. GROSSSPRENGUN UND MIKROSEISMIK

    Directory of Open Access Journals (Sweden)

    E. HARDTWIG

    1956-06-01

    Full Text Available Uéber die bei Sprengungen entstelienden Periodenspektren ist noch
    wenig bekannt, trotzdem in jedem Jahre Tausende von Sprengungen
    registriert werden. Die wenigen Arbeiten, die zu diesem Gegenstand erscliienen
    sind, stellen nur erste Versuche dar, den Aufbau der Spektren
    zu erklaren. Wàhrend etwa George Morris (* vorwiegend die bei
    Sprengungen si eh abspielenden Detonationsvorgànge zum Ausgangspunkt
    der Untersuchung macht, ist es bei IT. Menzel (2 die Interferenz von
    Primàrwelle und reflektierter Welle, deren Einfluss auf die Gestalt
    des Spektrums untersucht wird.

  13. Five-group cytogenetic risk classification, monosomal karyotype, and outcome after hematopoietic cell transplantation for MDS or acute leukemia evolving from MDS

    Science.gov (United States)

    Scott, Bart L.; Fang, Min; Shulman, Howard M.; Gyurkocza, Boglarka; Myerson, David; Pagel, John M.; Platzbecker, Uwe; Ramakrishnan, Aravind; Radich, Jerald P.; Sandmaier, Brenda M.; Sorror, Mohamed; Stirewalt, Derek L.; Wilson, Wendy A.; Storb, Rainer; Appelbaum, Frederick R.; Gooley, Ted

    2012-01-01

    Clonal cytogenetic abnormalities are a major risk factor for relapse after hematopoietic cell transplantation (HCT) for myelodysplastic syndrome (MDS). We determined the impact of the recently established 5-group cytogenetic classification of MDS on outcome after HCT. Results were compared with the impact of the International Prognostic Scoring System (IPSS) 3 cytogenetic risk groups, and the additional effect of a monosomal karyotype was assessed. The study included data on 1007 patients, 1-75 years old (median 45 years), transplanted from related (n = 547) or unrelated (n = 460) donors. Various conditioning regimens were used, and marrow, peripheral blood, or cord blood served as stem cell source. Both IPSS and 5-group cytogenetic risk classifications were significantly associated with post-HCT relapse and mortality, but the 5-group classification discriminated more clearly among the lowest- and highest-risk patients. A monosomal karyotype tended to further increase the rates of relapse and mortality, even after considering the IPSS or 5-group classifications. In addition, the pathologic disease category correlated with both relapse and mortality. Mortality was also impacted by patient age, donor type, conditioning regimen, platelet count, and etiology of MDS. Although mortality declined significantly in recent years, novel strategies are needed to overcome the barrier of high-risk cytogenetics. PMID:22767498

  14. Sibirien zwischen Kollaps und Kontinuitaet

    OpenAIRE

    Gray, Patty A.

    2002-01-01

    Sibirien ist ein Mythos: endlose Weiten, klirrende Kälte, Straflager, aber auch scheinbar unerschöpfliche Naturreichtümer und Bodenschätze. Für die dort lebenden indigenen Völker des Nordens ist Rentierhaltung neben Jagd und Fischfang nach wie vor zentraler Teil der Lebensgrundlage. Wie sich diese seit dem Zusammenbruch der Sowjetunion verändert hat, untersucht die Sibiriengruppe am MAX-PLANCK-INSTITUT FÜR ETHNOLOGISCHE FORSCHUNG in Halle. Deren Mitglieder DR. PATTY A. GRAY und...

  15. Diabetes mellitus und endotheliale Dysfunktion

    Directory of Open Access Journals (Sweden)

    Tripolt N

    2010-01-01

    Full Text Available Diabetes mellitus Typ 2 betrifft heute bereits ca. 300 Millionen Menschen weltweit und die Prognosen für die nächsten Jahre sagen noch einen deutlichen Anstieg voraus. Das Risiko für kardiovaskuläre Ereignisse ist bei Typ-2-Diabetikern deutlich gesteigert und stellt somit die Haupttodesursache in diesem Patientenkollektiv dar. Die endotheliale Dysfunktion ist eine frühe Stufe auf dem Weg zum atherothrombotischen Ereignis und ein potenziell reversibler Zustand. Dieser Artikel soll einen Überblick über die Pathogenese, die Möglichkeiten der Messung sowie die therapeutischen Optionen zur Verbesserung der Endothelfunktion bei Diabetikern geben.

  16. AML1/ETO trans-activates c-KIT expression through the long range interaction between promoter and intronic enhancer.

    Science.gov (United States)

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

    2018-04-01

    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.

  17. Characteristics, clinical outcome, and prognostic significance of IDH mutations in AML.

    Science.gov (United States)

    DiNardo, Courtney D; Ravandi, Farhad; Agresta, Sam; Konopleva, Marina; Takahashi, Koichi; Kadia, Tapan; Routbort, Mark; Patel, Keyur P; Mark Brandt; Pierce, Sherry; Garcia-Manero, Guillermo; Cortes, Jorge; Kantarjian, Hagop

    2015-08-01

    The pathophysiology of IDH mutations in tumorigenesis is increasingly described, yet the prognostic significance of IDH1 and IDH2 mutations in AML remains controversial. The primary objective of this study was to define the natural history and prognosis of patients with AML and IDH1 or IDH2 mutations and provide historical survival expectations. A total of 826 patients treated from 2010 to 2014 at a single institution were evaluated, including 167 patients (20%) with AML and IDH1 or IDH2 mutations. Median age was 62 years (range 18-92). There were 59 IDH1-R132, 83 IDH2-R140, and 23 IDH2-R172 mutations. Clinicopathologic characteristics associated with IDH-mutations included older age, less frequent therapy-related status, and increased incidence of intermediate-risk cytogenetics, FLT3-ITD mutations, and NPM1 mutations. Remission rates (CR/CRi) by AML treatment status were: induction, 68%; Salvage-1 (S1), 42%; and Salvage-2 and beyond (S2+), 27%. No difference in response was identified by IDH mutation status. Similarly, overall survival (OS) was not dependent on IDH status within any cohort. The median OS was 15.4 months in induction, 8.7 months in S1, and 4.8 months in S2+. This analysis defines the clinical outcome associated with IDH-mutations in both the front-line and salvage AML treatment settings, and confirms that response rate and OS for both IDH-mutated and IDH wild-type AML patients is comparable. This provides contemporary data to be used for comparison with results of novel investigational (e.g., selective IDH inhibitor) strategies. © 2015 Wiley Periodicals, Inc.

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

    OpenAIRE

    Schelp, Joachim; Winter, Robert

    2002-01-01

    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. Arbeitsmarktindikatoren: Definition und Erhebung nach nationaler und EU-Methode

    OpenAIRE

    Biffl, Gudrun

    1999-01-01

    Die statistische Beobachtung und Darstellung des Arbeitsmarktgeschehens zählt zu den grundlegenden Aufgaben des Arbeitsmarktservice Österreich. Gerade die Messung bzw. Ermittlung von Erwerbs-, Beschäftigungs- oder Arbeitslosenquoten und die dafür verwendeten Indikatoren stehen immer wieder im Brennpunkt heftiger Diskussionen. Das Wirtschaftsforschungsinstitut (WIFO) in Wien führte im Auftrag der Bundesgeschäftsstelle des AMS Österreich eine umfassende Analyse dieser Problematik durch. Ergebni...

  20. Gemtuzumab ozogamicin as postconsolidation therapy does not prevent relapse in children with AML

    DEFF Research Database (Denmark)

    Hasle, Henrik; Abrahamsson, Jonas; Forestier, Erik

    2012-01-01

    There are no data on the role of postconsolidation therapy with gemtuzumab ozogamicin (GO; Mylotarg) in children with acute myeloid leukemia (AML). The NOPHO-AML 2004 protocol studied postconsolidation randomization to GO or no further therapy. GO was administered at 5 mg/m(2) and repeated after 3...... neutropenia followed 95% and febrile neutropenia 40% of the GO courses. Only a moderate decline in platelet count and a minor decrease in hemoglobin occurred. Relapse occurred in 24 and 25 of those randomized to GO or no further therapy. The median time to relapse was 16 months versus 10 months...

  1. An Implementation and Evaluation of the AMLS Method for SparseEigenvalue Problems

    Energy Technology Data Exchange (ETDEWEB)

    Gao, Weiguo; Li, Xiaoye S.; Yang, Chao; Bai, Zhaojun

    2006-02-14

    We describe an efficient implementation and present aperformance study of an algebraic multilevel sub-structuring (AMLS)method for sparse eigenvalue problems. We assess the time and memoryrequirements associated with the key steps of the algorithm, and compareitwith the shift-and-invert Lanczos algorithm in computational cost. Oureigenvalue problems come from two very different application areas: theaccelerator cavity design and the normal mode vibrational analysis of thepolyethylene particles. We show that the AMLS method, when implementedcarefully, is very competitive with the traditional method in broadapplication areas, especially when large numbers of eigenvalues aresought.

  2. ELMO1 is upregulated in AML CD34+ stem/progenitor cells, mediates chemotaxis and predicts poor prognosis in normal karyotype AML.

    Directory of Open Access Journals (Sweden)

    Marta E Capala

    Full Text Available Both normal as well leukemic hematopoietic stem cells critically depend on their microenvironment in the bone marrow for processes such as self-renewal, survival and differentiation, although the exact pathways that are involved remain poorly understood. We performed transcriptome analysis on primitive CD34+ acute myeloid leukemia (AML cells (n = 46, their more differentiated CD34- leukemic progeny, and normal CD34+ bone marrow cells (n = 31 and focused on differentially expressed genes involved in adhesion and migration. Thus, Engulfment and Motility protein 1 (ELMO1 was identified amongst the top 50 most differentially expressed genes. ELMO1 is a crucial link in the signaling cascade that leads to activation of RAC GTPases and cytoskeleton rearrangements. We confirmed increased ELMO1 expression at the mRNA and protein level in a panel of AML samples and showed that high ELMO1 expression is an independent negative prognostic factor in normal karyotype (NK AML in three large independent patient cohorts. Downmodulation of ELMO1 in human CB CD34+ cells did not significantly alter expansion, progenitor frequency or differentiation in stromal co-cultures, but did result in a decreased frequency of stem cells in LTC-IC assays. In BCR-ABL-transduced human CB CD34+ cells depletion of ELMO1 resulted in a mild decrease in proliferation, but replating capacity of progenitors was severely impaired. Downregulation of ELMO1 in a panel of primary CD34+ AML cells also resulted in reduced long-term growth in stromal co-cultures in two out of three cases. Pharmacological inhibition of the ELMO1 downstream target RAC resulted in a severely impaired proliferation and survival of leukemic cells. Finally, ELMO1 depletion caused a marked decrease in SDF1-induced chemotaxis of leukemic cells. Taken together, these data show that inhibiting the ELMO1-RAC axis might be an alternative way to target leukemic cells.

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

    Science.gov (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

    2015-03-19

    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.

  4. Deszensusoperationen mit und ohne Gewebeersatz: Komplikations- und Rezidivmanagement

    Directory of Open Access Journals (Sweden)

    Tunn R

    2008-01-01

    Full Text Available Ein Deszensus soll erst dann operativ korrigiert werden, wenn er einen Leidensdruck verursacht und konservative Behandlungsmethoden ausgeschöpft wurden. In der Primärsituation hat die Rekonstruktion körpereigener Faszienstrukturen Priorität. Werden Zystound Rektozele durch zentrale Fasziendefekte bedingt, werden diese durch die vaginale Faszienrekonstruktion korrigiert, bei einer Damminsuffizienz wird die Rektozelenkorrektur mit der Dammrekonstruktion kombiniert. Ventrale Lateraldefekte zeigen sonographisch eine Hypermobilität von Urethra und Harnblase, bei der vaginalen Einstellung stellen sich die Rugae vaginales erhalten dar, hier bietet sich die Kolposuspension mit lateraler Rekonstruktion an. In der Rezidivsituation ist die Verwendung von Gewebeersatz sinnvoll. Als Gewebeersatz kommen allogene und xenogene Biomaterialien und alloplastische resorbierbare bzw. nicht resorbierbare Netzstrukturen zur Anwendung. Trägt man dem aktuellen Stand der Literatur und den klinischen Erfahrungen Rechnung, geht der Trend zum Einsatz alloplastischer, nicht resorbierbarer Polypropylennetze Typ I nach Amid (grobporig, monophil, leichtgewichtig: ca. 25–35 g/m². Defekte Level I können erfolgreich abdominal durch Kolposakropexie, Zysto- und Rektozelen bevorzugt vaginal durch ventrale transobturatorische bzw. dorsale transischioanale Netzeinlagen korrigiert werden.

  5. NOTCH2 and FLT3 gene mis-splicings are common events in patients with acute myeloid leukemia (AML): new potential targets in AML.

    Science.gov (United States)

    Adamia, Sophia; Bar-Natan, Michal; Haibe-Kains, Benjamin; Pilarski, Patrick M; Bach, Christian; Pevzner, Samuel; Calimeri, Teresa; Avet-Loiseau, Herve; Lode, Laurence; Verselis, Sigitas; Fox, Edward A; Galinsky, Ilene; Mathews, Steven; Dagogo-Jack, Ibiayi; Wadleigh, Martha; Steensma, David P; Motyckova, Gabriela; Deangelo, Daniel J; Quackenbush, John; Tenen, Daniel G; Stone, Richard M; Griffin, James D

    2014-05-01

    Our previous studies revealed an increase in alternative splicing of multiple RNAs in cells from patients with acute myeloid leukemia (AML) compared with CD34(+) bone marrow cells from normal donors. Aberrantly spliced genes included a number of oncogenes, tumor suppressor genes, and genes involved in regulation of apoptosis, cell cycle, and cell differentiation. Among the most commonly mis-spliced genes (>70% of AML patients) were 2, NOTCH2 and FLT3, that encode myeloid cell surface proteins. The splice variants of NOTCH2 and FLT3 resulted from complete or partial exon skipping and utilization of cryptic splice sites. Longitudinal analyses suggested that NOTCH2 and FLT3 aberrant splicing correlated with disease status. Correlation analyses between splice variants of these genes and clinical features of patients showed an association between NOTCH2-Va splice variant and overall survival of patients. Our results suggest that NOTCH2 and FLT3 mis-splicing is a common characteristic of AML and has the potential to generate transcripts encoding proteins with altered function. Thus, splice variants of these genes might provide disease markers and targets for novel therapeutics.

  6. Jung und Alt im Dialog

    Directory of Open Access Journals (Sweden)

    Caroline Baetge

    2012-04-01

    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.

  7. Renaturierung und Management von Heiden

    Science.gov (United States)

    Härdtle, Werner; Assmann, Thorsten; van Diggelen, Rudy; von Oheimb, Goddert

    Heiden zählen zu den ältesten und besonders reizvollen Kulturlandschaften Nordwesteuropas. Sie sind bezeichnend für nährstoffarme Böden in wintermilden Gebieten mit hohen Sommerniederschlägen. Während Heiden vor wenigen Jahrhunderten noch weit verbreitet und für manche Landschaften sogar prägend waren, hat sich ihr Areal heute auf wenige, meist in Naturschutzgebieten gelegene Restbestände verkleinert. Zu diesem Rückgang haben maßgeblich Änderungen der Landnutzung, aber auch Nährstoffeinträge aus umgebenden Agrarflächen und atmogene Depositionen beigetragen. In den meisten Ländern der Europäischen Union sind Heiden heute gesetzlich geschützte Ökosysteme, da diese, neben ihrem Erholungswert für den Menschen, Pflanzen- und Tierarten beherbergen, die außerhalb von Heiden nicht oder kaum überlebensfähig sind.

  8. Phase I Trial of the Selective Inhibitor of Nuclear Export, KPT-330, in Relapsed Childhood ALL and AML

    Science.gov (United States)

    2018-03-05

    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

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

    Directory of Open Access Journals (Sweden)

    Johannes Fromme

    2008-01-01

    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

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

    Science.gov (United States)

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

    2005-08-01

    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.

  11. Assessing the Mechanisms of MDS and Its Transformation to Leukemia in a Novel Humanized Mouse

    Science.gov (United States)

    2016-05-01

    for reducing this burden to Department of Defense, Washington Headquarters Services, Directorate for Information Operations and Reports (0704-0188...grade MDS with replication of the disease geno- and phenotypes. Inventions, Patents and Licences N/A Reportable Outcomes N/A Other

  12. Zuwanderungsmotive und Erwerbseinkommen von Migranten

    OpenAIRE

    Brenke, Karl; Constant, Amelie; Zimmermann, Klaus F.

    2005-01-01

    Um den Rückgang des Erwerbspersonenpotentials aufgrund unzureichender Geburtenraten in nahezu allen Ländern der Europäischen Union abzubremsen, sind Zuwanderungen unverzichtbar. Anfang dieses Jahres hat die EU-Kommission ein ,,Grünbuch" vorgelegt, das auf eine stärkere Vereinheitlichung der bisher im Wesentlichen nationalen Migrationspolitiken zielt und in dem allgemeine Regeln und Kriterien für Zuwanderungen in die Gemeinschaft gefordert werden. Seitens der EU wurde in den letzten Jahren auc...

  13. Irritation durch Waschen und Desinfizieren

    OpenAIRE

    Weimer, Caroline Maria

    2006-01-01

    Ziel dieser Studie war die Irritation der Haut, hervorgerufen durch alkoholische Desinfektionsmittel und das Detergens Natriumlaurylsulfat (0,5% NLS) in einem repetitiven Testdesign zu untersuchen. Mittels nicht invasiver Untersuchungsmethoden quantifizierten wir die irritativen Effekte von Sterillium®, 2-Propanol 45% v/v, 1-Propanol 30% v/v, welches die alkoholische Grundlage von Sterillium® darstellt sowie von Wasser und NLS 0,5...

  14. Interconnectedness und digitale Texte

    Directory of Open Access Journals (Sweden)

    Detlev Doherr

    2013-04-01

    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

  15. Brazing, high temperature brazing and diffusion welding. Lectures and posters; Hart- und Hochtemperaturloeten und Diffusionsschweissen. Vortraege und Posterbeitraege

    Energy Technology Data Exchange (ETDEWEB)

    Anon.

    1998-12-01

    This collection of papers contains the following main aspects: Brazing in traffic and transport, brazing in refrigeration and air conditioning and other applications, materials development, process development, diffusion bonding, brazing of high-performance materials and composite materials, quality and testing. (orig./MM) [Deutsch] Dieser Tagungsband enthaelt folgende Themenschwerpunkte: Loeten in der Verkehrstechnik, Loeten in der Kaelte- und Klimatechnik und andere Anwendungen, Werkstoffentwicklung, Prozessentwicklung, Diffusionsfuegen, Loeten von Hochleistungswerkstoffen und Verbundwerkstoffen, Qualitaet und Pruefung. (orig./MM)

  16. Gender-, age- and race/ethnicity-based Differential Item Functioning (DIF) analysis of MDS-UPDRS

    Science.gov (United States)

    Goetz, Christopher G.; Liu, Yuanyuan; Stebbins, Glenn T.; Wang, Lu; Tilley, Barbara C.; Teresi, Jeanne A.; Merkitch, Douglas; Luo, Sheng

    2016-01-01

    Objective Assess MDS-UPDRS items for gender-, age-, and race/ethnicity-based Differential Item Functioning. Background Assessing Differential Item Functioning is a core rating scale validation step. For the MDS-UPDRS, Differential Item Functioning occurs if item-score probability among people with similar levels of parkinsonism differ according to selected covariates (gender, age, race/ethnicity). If the magnitude of Differential Item Functioning is clinically relevant, item-score interpretation must consider influences by these covariates. Differential Item Functioning can be Non-uniform (covariate variably influences an item-score across different levels of parkinsonism) or Uniform (covariate influences an item-score consistently over all levels of parkinsonism. Methods Using the MDS-UPDRS translation database of over 5,000 PD patients from fourteen languages, we tested gender-, age-, and race/ethnicity-based Differential Item Functioning. To designate an item as having clinically relevant Differential Item Functioning, we required statistical confirmation by two independent methods, along with a McFadden pseudo-R2 magnitude statistic greater than “negligible.” Results Most items showed no gender-, age- or race/ethnicity-based Differential Item Functioning. When Differential Item Functioning was identified, the magnitude statistic was always in the “negligible” range, and the scale level impact was minimal. Conclusions The absence of clinically relevant Differential Item Functioning across all items and all Parts of MDS-UPDRS is strong evidence that the scale can be used confidently. As studies of Parkinson's disease increasingly involve multinational efforts and the MDS-UPDRS has several validated non-English translations, the findings support the scale's broad applicability in populations with varying gender, age, and race/ethnicity distributions. PMID:27943473

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

    Directory of Open Access Journals (Sweden)

    Lübbert Michael

    2009-09-01

    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.

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

    Science.gov (United States)

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

    2017-04-01

    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.

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

    Directory of Open Access Journals (Sweden)

    Shanmin Zhao

    2014-01-01

    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.

  20. Gute Inhalte produzieren und Rahmen schaffen

    DEFF Research Database (Denmark)

    Pogner, Karl-Heinz

    2004-01-01

    Informationschefs sowie Kommunikationsberater wurden befragt zu: Kommunikati-onsstrategie, Nutzung digitaler Kommunikationsformen und gewünschte Mitarbeiterqualifikationen (2, 3). Die wichtigsten Ergebnisse lauten: Das Intranet soll besser strukturiert und vereinfacht wer-den, ausserdem soll es vermehrt als Forum...

  1. Gesellschaftlicher Wandel und der Umbau der Jugendhilfe

    OpenAIRE

    Plankensteiner, Annette

    2013-01-01

    Gesellschaftlicher Wandel und der Umbau der Jugendhilfe. - In: Flexible Erziehungshilfen : Grundlagen und Praxis des "Augsburger Weges" zur Modernisierung der Jugendhilfe / Annette Plankensteiner ... (Hrsg.). - Weinheim u.a. : Beltz Juventa, 2013. - S. 14-32

  2. Prognostic Value of RUNX1 Mutations in AML: A Meta-Analysis

    Science.gov (United States)

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

    2018-02-26

    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

  3. Budget impact analysis of CYP2C19-guided voriconazole prophylaxis in AML.

    Science.gov (United States)

    Mason, Neil T; Bell, Gillian C; Quilitz, Rod E; Greene, John N; McLeod, Howard L

    2015-11-01

    The objective of this study was to determine the economic impact of proactive, CYP2C19 genotype-guided voriconazole prophylaxis in AML. An Excel-based model was created to project the cost of treating a simulated cohort of severely neutropenic AML patients undergoing antifungal prophylaxis. The model compares (i) standard prophylactic dosing with voriconazole and (ii) CYP2C19 genotyping of all AML patients to guide voriconazole dosing and prescribing. Based on the model, genotype-guided dosing of voriconazole conservatively spares 2.3 patients per year from invasive fungal infections. Implementing proactive genotyping of all AML patients in a simulated 100 patient cohort is expected to save a total of $41467 or $415 per patient. The model, based on the robust literature of clinical and economic data, predicts that proactive genotype-guided voriconazole prophylaxis is likely to yield modest cost savings while improving patient outcomes. The primary driver of savings is the avoidance of expensive antifungal treatment and extended hospital stays, costing $30 952 per patient, in patients succumbing to fungal infection. © The Author 2015. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  4. NK cell-mediated killing of AML blasts. Role of histamine, monocytes and reactive oxygen metabolites

    Energy Technology Data Exchange (ETDEWEB)

    Brune, M.; Mellqvist, U.H. [Sahlgren`s Univ. Hospital, Dept. of Medicine, Haematology Section, Goeteborg (Sweden); Hansson, M.; Hermodsson, S.; Hellstrand, K. [Sahlgren`s Univ. Hospital, Dept. of Virology, Goeteborg (Sweden)

    1996-10-01

    Blasts recovered from patients with acute myelogenous leukaemia (AML) were lysed by heterologeous natural killer (NK) cells treated with NK cell-activating cytokine-induced killing of AML blasts was inhibited by monocytes, recovered from peripheral blood by counterflow centrifugal elutriation. Histamine, at concentrations exceeding 0.1 {mu}M, abrogated the monocyte-induced inhibition of NK cells; thereby, histamine and IL-2 or histamine and IFN-{alpha} synergistically induced NK cell-mediated destruction of AML blasts. The effect of histamine was completely blocked by the histamine H2-receptor (H2R) antagonist ranitidine but not by its chemical control AH20399AA. Catalase, a scavenger of reactive oxygen metabolites (ROM), reversed the monocyte-induced inhibition of NK cell-mediated killing of blast cells, indicating that the inhibitory signal was mediated by products of the respiratory burst of monocytes. It is concluded that (i) monocytes inhibit anti-leukemic properties of NK cells, (ii) the inhibition is conveyed by monocyte-derived ROM, and (iii) histamine reverses the inhibitory signal and, thereby, synergizes with NK cell-activating cytokines to induce killing of AML blasts. (au) 19 refs.

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

    DEFF Research Database (Denmark)

    Tawana, Kiran; Wang, Jun; Renneville, Aline

    2015-01-01

    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...

  6. Investigational BET bromodomain protein inhibitors in early stage clinical trials for acute myelogenous leukemia (AML).

    Science.gov (United States)

    Braun, Thorsten; Gardin, Claude

    2017-07-01

    Acute myelogenous leukemia (AML) is a heterogeneous group of malignancies driven by genetic mutations and deregulated epigenetic control. Relapse/refractory disease remains frequent in younger patients and even more so in older patients, including treatment with epigenetic drugs in this age group, mainly with hypomethylating agents. New treatment strategies are urgently needed. The recent discovery that epigenetic readers of the bromodomain (BRD) and extraterminal (BET) protein family, are crucial for AML maintenance by transcription of oncogenic c-MYC lead to rapid development of BET inhibitors entering clinical trials. Areas covered: We provide a critical overview using main sources for the use of BET inhibitors in AML treatment. Limits of this treatment approach including resistance mechanisms and future directions including development of new generation BET inhibitors and combination strategies with other drugs are detailed. Expert opinion: BET inhibitors were expected to overcome limits of conventional treatment in patients as impressive in vitro data emerged recently in well-characterized AML subsets, including those associated with poor risk characteristics in the clinic. Nevertheless single activity of BET inhibitors appears to be modest and resistance mechanisms were already identified. BET inhibitors with alternative mechanisms of action and/or combination strategies with epigenetic drugs should be tested.

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

    DEFF Research Database (Denmark)

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

    2012-01-01

    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...

  8. Histological and immunohistochemical features of gingival enlargement in a patient with AML

    NARCIS (Netherlands)

    Sonoi, N.; Soga, Y.; Maeda, H.; Ichimura, K.; Yoshino, T.; Aoyama, K.; Fujii, N.; Maeda, Y.; Tanimoto, M.; Logan, R.; Raber-Durlacher, J.; Takashiba, S.

    2012-01-01

    Here, we discuss the pathophysiology of leukemia-associated gingival enlargement based on a case of acute myelomonocytic leukemia (AML-M4) with typical gingival enlargement. Uniquely, this patient was well enough to allow full periodontal examination and incisional gingival biopsy to be performed

  9. Überlegungen zu den Ursachen und Wirkmechanismen des Konsums von Gewaltdarstellungen bei Kindern und Jugendlichen

    OpenAIRE

    Rauchfleisch, Udo

    1997-01-01

    Der Autor geht den Fragen nach, warum Kinder und Jugendliche in der Gegenwart z.T. intensiv Gewaltdarstellungen konsumieren und welches die Auswirkungen dieses Konsums sind. Die Motive des Gewaltkonsums sind u.a. Kompensation und Flucht vor Alltagsproblemen und vor innerer Leere, Identifikation mit großartigen Helden, das Erleben von Angst-Lust, Abgrenzung und Protest gegenüber der Elterngeneration sowie Mutprobe zur Etablierung des sozialen Status in der peer group. Die Wirkungen, die Gewalt...

  10. Ambulante und stationäre Krisenintervention bei Kindern und Jugendlichen

    OpenAIRE

    Deutschmann-Barth, Katharina

    2002-01-01

    Einleitung: In der vorliegenden Studie werden, aufbauend auf zwei frühere Studien aus der Abteilung für Psychiatrie und Psychotherapie im Kindes- und Jugendalter der Universitätsklinik Tübingen, stationäre und ambulante Kriseninterventionen unter verschiedenen Blickwinkeln miteinander verglichen. Ein Schwerpunkt der Arbeit liegt in der Darstellung des Vorgehens bei ambulanten und stationären Kriseninterventionen , sowie des jeweiligen Aufwandes der für Therapie und Betreuung der Krisenpatient...

  11. 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.

    2017-01-01

    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

  12. Bioverfügbarkeit und Metabolismus von Flavonoiden

    OpenAIRE

    Wittig, Jörg

    2002-01-01

    Ziel der vorliegenden Arbeit war die Entwicklung, Optimierung und Validierung von phyto- und bioanalytischen Analysemethoden. Dabei wurden exemplarische Fragestellungen aus dem Themenkreis Phytotherapie bzw. Bioverfügbarkeit und Metabolismus von einfachen und Polyphenolen bearbeitet. Quercetin und seine Derivate: Zur qualitativen Analyse der Flavonoide und -derivate in einem Trockenextraktgemisch aus Birkenblättern, Goldrutenkraut und Orthosiphonblättern wurde eine HPLC- UV/VIS Methode entwic...

  13. Data Science und Analytics in Bibliotheken

    Directory of Open Access Journals (Sweden)

    José Luis Preza

    2017-09-01

    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.

  14. Zum Stand und den Perspektiven der allgemeinsprachlichen ...

    African Journals Online (AJOL)

    Mev. R.B. Ruthven

    Kritische Anmerkun- gen zur neueren und neuesten Wörterbuchforschung. Lexicographica 17: 217-248. Wiegand, Herbert Ernst. 2001a. Sprachkontaktwörterbücher, Typen, Funktionen, Strukturen. Igla,. Birgit, Pavel Petkov und Herbert Ernst Wiegand (Hrsg.). 2001. Theoretische und praktische. Probleme der Lexikographie.

  15. Zustand und Perspektiven der Kapitalmarktfinanzierung in Deutschland

    DEFF Research Database (Denmark)

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

    2016-01-01

    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...

  16. Verbraucher und Grüne Gentechnik:

    DEFF Research Database (Denmark)

    Scholderer, Joachim

    2008-01-01

    In den Jahren 2001 und 2002 hat das Bundesministerium für Verbraucherschutz, Ernährung und Landwirtschaft ein Diskursprojekt zur Grünen Gentechnik durchgeführt. Das Projekt brachte politische Akteure, Vertreter gesellschaftlicher Interessengruppen und wissenschaftliche Experten in Workshops zusam...

  17. Mensch und Maschine in Übersetzungsprozessen

    DEFF Research Database (Denmark)

    Hansen, Gyde

    2014-01-01

    Wie kann der optimale, kombinierte Übersetzungsprozess von Mensch und Maschine aussehen, bei dem professionelle Übersetzerinnen sich auf Maschinenübersetzungen stützen können. Ihr Arbeitseinsatz und die Qualität des Übersetzungsprodukts müssen übereinstimmen und die Zieltexte sollen gebrauchstaug...

  18. Sensorische Lebensmitteluntersuchung und Prüfmethoden

    Science.gov (United States)

    Busch-Stockfisch, Mechthild

    Die Sensorik hat in den letzten Jahren eine dynamische Entwicklung gemacht. Wurde sie früher in erster Linie als analytische Methode und zur Qualitätsbeurteilung und Qualitätssicherung eingesetzt, um Produkteigenschaften mit den Sinnen (Sehen, Riechen, Schmecken, Fühlen) zu messen, ist ihr Einsatzgebiet heute vielfältiger und variabler.

  19. MDS shows a higher expression of hTERT and alternative splice variants in unactivated T-cells.

    Science.gov (United States)

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

    2016-11-01

    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.

  20. Validity of the RAI-MDS for ascertaining diabetes and comorbid conditions in long-term care facility residents.

    Science.gov (United States)

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

    2014-01-15

    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.

  1. GIS und Fernerkundung für Landschaftsmonitoring und Landschaftsplanung

    Science.gov (United States)

    Blaschke, Thomas

    2002-09-01

    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.

  2. Beobachtung von Klima und Klimawandel in Mitteleuropa und Deutschland

    Science.gov (United States)

    Kaspar, Frank; Mächel, Hermann; Jacob, Daniela; Kottmeier, Christoph

    Wetterdienste und andere Forschungseinrichtungen in Deutschland und seinen Nachbarländern beobachten seit dem 19. Jahrhundert, wie sich das Klima in Mitteleuropa verändert. Auf Basis der gesammelten Beobachtungen lassen sich Aussagen über die Klimaentwicklung in Deutschland treffen: Die Daten erlauben Beschreibungen der Atmosphäre vom täglichen Wetter bis zu mehreren Jahrzehnten, über die sich das Klima ändert. Darüber hinaus liefern die Langzeitbeobachtungen auch Datensätze, welche die Überprüfung von Klimamodellen ermöglichen. Das Kapitel stellt schwerpunktmäßig die Geschichte der Beobachtungen sowie die tatsächlich gemessene Veränderung verschiedener Klimakenngrößen für Deutschland dar. Außerdem werden Nutzbarkeit und Einschränkungen der Datensätze für die Evaluation der Klimamodelle bewertet.

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

    Science.gov (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

    2014-05-08

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

    Science.gov (United States)

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

    2014-04-01

    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 TPO than the osteoblasts derived from normal control BMSCs (P TPO level and c-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.

  5. Einflüsse von Trennung und neuer Partnerschaft der Eltern. Ein Vergleich von Jungen und Mädchen in Ost- und Westdeutschland

    OpenAIRE

    Walper, Sabine

    2002-01-01

    Die vorliegende Studie vergleicht die Befindlichkeit, Sozial- und Kompetenzentwicklung von Kindern und Jugendlichen aus Kern-, Mutter- und Stieffamilien. Hierbei wird zunächst nach differentiellen Effekten des Familientyps in West- und Ostdeutschland sowie in Abhängigkeit von Alter und Geschlecht gefragt. Danach wird geprüft, inwieweit verschiedene familiäre Belastungsfaktoren mögliche Effekte des Familientyps erklären. Die Daten stammen aus standardisierten Befragungen von 654 Kindern und Ju...

  6. Heterogeneity within AML with CEBPA mutations; only CEBPA double mutations, but not single CEBPA mutations are associated with favourable prognosis

    OpenAIRE

    Pabst, T; Eyholzer, M; Fos, J; Mueller, B U

    2009-01-01

    CCAAT/enhancer binding protein alpha (CEBPA) mutations in AML are associated with favourable prognosis and are divided into N- and C-terminal mutations. The majority of AML patients have both types of mutations. We assessed the prognostic significance of single (n=7) and double (n=12) CEBPA mutations among 224 AML patients. Double CEBPA mutations conferred a decisively favourable overall (P=0.006) and disease-free survival (P=0.013). However, clinical outcome of patients with single CEBPA mut...

  7. [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-

    2013-01-01

    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

  8. Restaurierung von Seen und Renaturierung von Seeufern

    Science.gov (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.

  9. Ethik, Recht und Theologie. Reproduktionstechnologien in Polen

    Directory of Open Access Journals (Sweden)

    Susanne Lettow

    2006-03-01

    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.

  10. Grundlagen der Nieren- und Leberdialyse

    Science.gov (United States)

    Schreiber, Christian; Al-Chalabi, Ahmed N. Ar.; Tanase, Oana; Kreymann, Bernhard

    Die Dialyse ist ein künstliches Blutreinigungsverfahren, das sowohl mit der Nachahmung physiologischer Vorgänge als auch mit der Benutzung bestimmter physikalisch- chemischer Gesetze arbeitet. Ihre technische Umsetzung in einer Dialysemaschine sowie chirurgische und internistische Interventionen gehören zu dem Zusammenspiel unterschiedlicher Disziplinen, die eine Dialyse ermöglichen. Die Grundlagen des Dialyseverfahrens, die Maschine und die Unterschiede von Nieren- und Leberdialyse sollen im Folgenden erklärt werden. Heute besteht in der Bundesrepublik Deutschland bei ca. 55.000 Patienten ein chronisch dialysepflichtiges Nierenversagen (Stand 2005). Das Leben dieser Patienten kann mit der Dialyse um Jahrzehnte verlängert werden. Damit ist die Nierendialyse eines der erfolgreichsten medizintechnischen Verfahren. Bei der Leberdialyse sind ebenbürtige Erfolge noch nicht erzielt worden. Umso wichtiger ist es, hier neue Wege zu finden, um auch für Leberpatienten ein effizientes Dialyseverfahren zu etablieren.

  11. Osteoporose und Genetik des Knochenstoffwechsels

    Directory of Open Access Journals (Sweden)

    Obermayer-Pietsch B

    2002-01-01

    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.

  12. CLILiG und Musikunterricht

    Directory of Open Access Journals (Sweden)

    Merle Jung

    2015-10-01

    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.

  13. GPA-MDS: A Visualization Approach to Investigate Genetic Architecture among Phenotypes Using GWAS Results.

    Science.gov (United States)

    Wei, Wei; Ramos, Paula S; Hunt, Kelly J; Wolf, Bethany J; Hardiman, Gary; Chung, Dongjun

    2016-01-01

    Genome-wide association studies (GWAS) have identified tens of thousands of genetic variants associated with hundreds of phenotypes and diseases, which have provided clinical and medical benefits to patients with novel biomarkers and therapeutic targets. Recently, there has been accumulating evidence suggesting that different complex traits share a common risk basis, namely, pleiotropy. Previously, a statistical method, namely, GPA (Genetic analysis incorporating Pleiotropy and Annotation), was developed to improve identification of risk variants and to investigate pleiotropic structure through a joint analysis of multiple GWAS datasets. While GPA provides a statistically rigorous framework to evaluate pleiotropy between phenotypes, it is still not trivial to investigate genetic relationships among a large number of phenotypes using the GPA framework. In order to address this challenge, in this paper, we propose a novel approach, GPA-MDS, to visualize genetic relationships among phenotypes using the GPA algorithm and multidimensional scaling (MDS). This tool will help researchers to investigate common etiology among diseases, which can potentially lead to development of common treatments across diseases. We evaluate the proposed GPA-MDS framework using a simulation study and apply it to jointly analyze GWAS datasets examining 18 unique phenotypes, which helps reveal the shared genetic architecture of these phenotypes.

  14. Kreuz und quer durch Deutschland

    DEFF Research Database (Denmark)

    Hellensberg, Christina

    2015-01-01

    Undervisningsforløbet Kreuz und quer durch Deutschland beskriver læringsmålstyret undervisning i faget tysk i 5. og 6. klasse, hvor der arbejdes med kompetenceområderne mundtlig kommunikation samt kultur og samfund. Forløbet er forskningsinformeret og afprøvet i en 5. klasse.......Undervisningsforløbet Kreuz und quer durch Deutschland beskriver læringsmålstyret undervisning i faget tysk i 5. og 6. klasse, hvor der arbejdes med kompetenceområderne mundtlig kommunikation samt kultur og samfund. Forløbet er forskningsinformeret og afprøvet i en 5. klasse....

  15. The development of integration mobile-based home care support systems: MDS-HC as an example.

    Science.gov (United States)

    Hsiao, Fang-Ying; Kuo, Yu-Yin; Chang, Polun; Chiehwen, Ed Hsu

    2008-11-06

    The MDS-HC (Minimum Data Set for Home Care Assessment Instrument) has been an effective home care evaluation instrument. However it was not yet accepted in Taiwan because it is too long for our over-burdened home care nurses. We developed integrated mobile-based home care support system using MDS-HC. The results showed that an integration mobile-based system can increase efficiency and reduce manual work.

  16. EVI and MDS/EVI are required for adult intestinal stem cell formation during postembryonic vertebrate development.

    Science.gov (United States)

    Okada, Morihiro; Shi, Yun-Bo

    2018-01-01

    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.

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

    Science.gov (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

    2013-10-01

    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.

  18. Th17 Cells Exhibit Antitumor Effects in MDS Possibly through Augmenting Functions of CD8+ T Cells.

    Science.gov (United States)

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

    2016-01-01

    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.

  19. Oncogenic fusion proteins expressed in immature hematopoietic cells fail to recapitulate the transcriptional changes observed in human AML

    DEFF Research Database (Denmark)

    Rapin, N; Porse, B T

    2014-01-01

    Reciprocal chromosomal translocations are observed in one-third of acute myeloid leukemia (AML) cases. Targeting and understanding the effects of the resulting aberrant oncogenic fusion proteins may help developing drugs against specific leukemic subtypes, as demonstrated earlier by the use of ATRA....... Surprisingly, we found that the gene-expression profiles of CD34+ human HSPCs transformed with the potent oncogenic fusion proteins AML-ETO or MLL-AF9, only weakly resembled those derived from primary AML samples. Hence, our work raises concerns as to the relevance of the use of in vitro transduced cells...... in acute promyelocytic leukemia. Hematopoietic stem/progenitor (HSPCs) cells transduced with oncogenic fusion genes are regarded as promising in vitromodels of their corresponding AML subtypes. Here, we critically assessed the potential of such in vitro models using an integrative bioinformatics approach...

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

    Index Scriptorium Estoniae

    Selart, Anti, 1973-

    2015-01-01

    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

  1. Editorial: Neue Medien und individuelle Leistungsdarstellung: Möglichkeiten und Grenzen von ePortfolios und eAssessments

    Directory of Open Access Journals (Sweden)

    Claudia de Witt

    2010-03-01

    Full Text Available Der Einsatz digitaler Medien in formellen Lernzusammenhängen (Schule, Hochschule, berufliche Bildung etc. bietet neue Möglichkeiten, die Kenntnisse und Kompetenzen Lernender darzustellen bzw. abzubilden. So sollen z.B. Instrumente wie E-Portfolios eine selbstbestimmtere Leistungsdarstellung ermöglichen: Lernende sollen ihren Lernprozess dokumentieren und reflektieren, sich ihrer Verantwortung für ihn bewusst werden und ihn im Idealfall selbst steuern, Lehrende nehmen dabei eine beratende und unterstützende Rolle ein. Allerdings sind die Erwartungen und Ansprüche an E-Portfolios sehr unterschiedlich; sie reichen von standardisierten, formalisierten Qualifikationsdarstellungen für den beruflichen Wettbewerbsmarkt bis hin zu individuellen Kompetenzprofilen. Zwar sind in Lehr-Lern-Arrangements weiterhin quantitative Bewertungen von Leistungen weit verbreitet, doch finden sich zunehmend auch qualitative Anteile z.B. durch den Einsatz von E-Portfolios. Dabei werden diese in bestehende Lehr- und Lernkulturen integriert, die sie gleichzeitig verändern. Die Frage ist auch, was mit E-Portfolios erreicht werden soll: Geht es um eine stärkere Förderung der Selbstlernkompetenz und um die Fähigkeit, sich eigenverantwortlich den Forderungen nach lebensbegleitendem Lernen stellen zu können? Sollen individuelle Stärken und Schwächen transparenter werden, um die eigene Reflexion von Bildungsreife wie auch deren Einschätzung und Bewertung durch Ausbildungspersonal zu erleichtern? Oder geht es um beides? Unter dem Oberbegriff E-Assessment dagegen lassen sich computer- bzw. internetgestützte Prüfungsformen (z.B. E-Klausuren zusammenfassen, die anders als E-Portfolios eine möglicherweise objektivere und vergleichbarere Bewertungsgrundlage für die Identifizierung, Darstellung und Reflexion individueller Leistungen bieten. Zu hinterfragen ist in jedem Fall, welchen Stellenwert Selbstreflexion und Selbststeuerung in immer stärker durchorganisierten

  2. A multigene array for measurable residual disease detection in AML patients undergoing SCT

    Science.gov (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

    2015-01-01

    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

  3. Effects of T-Cell Depletion on Allogeneic Hematopoietic Stem Cell Transplantation Outcomes in AML Patients

    Directory of Open Access Journals (Sweden)

    Gabriela Soriano Hobbs

    2015-03-01

    Full Text Available Graft versus host disease (GVHD remains one of the leading causes of morbidity and mortality associated with conventional allogeneic hematopoietic stem cell transplantation (HCT. The use of T-cell depletion significantly reduces this complication. Recent prospective and retrospective data suggest that, in patients with AML in first complete remission, CD34+ selected grafts afford overall and relapse-free survival comparable to those observed in recipients of conventional grafts, while significantly decreasing GVHD. In addition, CD34+ selected grafts allow older patients, and those with medical comorbidities or with only HLA-mismatched donors to successfully undergo transplantation. Prospective data are needed to further define which groups of patients with AML are most likely to benefit from CD34+ selected grafts. Here we review the history of T-cell depletion in AML, and techniques used. We then summarize the contemporary literature using CD34+ selection in recipients of matched or partially mismatched donors (7/8 or 8/8 HLA-matched, and provide a summary of the risks and benefits of using T-cell depletion.

  4. Potential for subsets of wt-NPM1 primary AML blasts to respond to retinoic acid treatment

    OpenAIRE

    Bunaciu, Rodica P.; MacDonald, Robert J.; Gao, Feng; Johnson, Lynn M.; Varner, Jeffrey D.; Wang, Xin; Nataraj, Sarah; Guzman, Monica L.; Yen, Andrew

    2017-01-01

    Acute myeloid leukemia (AML) has high mortality rates, perhaps reflecting a lack of understanding of the molecular diversity in various subtypes and a lack of known actionable targets. There are currently 12 open clinical trials for AML using combination therapeutic modalities including all-trans retinoic acid (RA). Mutant nucleophosmin-1, proposed as a possible marker for RA response, is the criterion for recruiting patients in three active RA phase 3 clinical trials. We tested the ability o...

  5. A pilot study on the usefulness of peripheral blood flow cytometry for the diagnosis of lower risk myelodysplastic syndromes: the "MDS thermometer".

    Science.gov (United States)

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

    2018-01-01

    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.

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

    LENUS (Irish Health Repository)

    Rishi, Loveena

    2014-04-10

    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.

  7. Familienpolitik, Bildung und Berufskarrieren von Müttern in Deutschland, USA und Schweden

    NARCIS (Netherlands)

    Grunow, D.; Aisenbrey, S.; Evertsson, M.

    2011-01-01

    Dieser Beitrag widmet sich der beruflichen Entwicklung von Müttern mit ungleichen Bildungsressourcen in international vergleichender Perspektive. Wir untersuchen die Strategien zur Vereinbarkeit von Berufskarrieren und Elternschaft in Deutschland, USA und Schweden für Frauen mit unterschiedlichem

  8. Perfektionistischer Liberalismus und Politischer Liberalismus

    Directory of Open Access Journals (Sweden)

    Nussbaum Martha C.

    2014-12-01

    Full Text Available Dieser Text ist ursprünglich 2011 unter dem Titel „Perfectionist Liberalism and Political Liberalism“ in Philosophy & Public Affairs 39 (1, 3–45, erschienen. Wir danken Martha Nussbaum sowie dem Verlag Wiley für die Erlaubnis zur Übersetzung und hoffen damit, zur weiteren Rezeption dieses wichtigen Textes beizutragen.

  9. 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...

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

    Index Scriptorium Estoniae

    Boetticher, Manfred von, 1947-

    2012-01-01

    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)

  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.

    Science.gov (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

    2017-06-01

    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. Einfluß von Ausdauersport und oralen Kontrazeptiva auf Knochenmasse, -dichte und -festigkeit

    OpenAIRE

    Nguedia, Christel

    2009-01-01

    Im Rahmen dieser Querschnittsstudie wurden die Effekte des Triathlontrainings (ET) verglichen und/oder kombiniert mit niedrigdosierten oralen Kontrazeptiva (OC) auf die Knochenmasse, -dichte und –festigkeit. 174 Frauen im Alter vom 18.-35. Lebensjahr wurden in vier Gruppen aufgeteilt nach den Faktoren Ausdauertraining und orale Kontrazeptiva. Die BMD von LWS (L2-4) und von der OSH wurde mittels eines DXA-Geräts gemessen. Verschiedene Variablen der peripheren quantitativen Computer Tomographie...

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

    Index Scriptorium Estoniae

    Narits, Raul, 1952-

    2008-01-01

    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)

  14. Knowledgebase Erwachsenenbildung: aktuelle Entwicklung und Geschichte der österreichischen Erwachsenenbildung. Erfahrbar, erforschbar und anwendbar

    OpenAIRE

    Vater, Stefan

    2007-01-01

    Die Knowledgebase Erwachsenenbildung ist eine umfassende Online-Plattform der österreichischen Erwachsenenbildung, die vom Verband Österreichischer Volkshochschulen und dem Österreichischen Volkshochschularchiv erstellt wurde. Das Projekt wurde vom Bundesministerium für Bildung, Wissenschaft und Kunst und dem Europäischen Sozialfond gefördert. In 42 verschiedenen Datenbanken wird eine breite Palette an Fachliteratur, Informationen zur Geschichte und Entwicklung der Erwachsenenbildung, Statist...

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

    OpenAIRE

    Kaltenhofer, Alice

    2009-01-01

    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...

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

    OpenAIRE

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

    2018-01-01

    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...

  17. Wahrnehmung und Bewältigung von Konflikten und die Stabilität von Partnerschaften

    OpenAIRE

    Arránz Becker, Oliver; Rüssmann, Kirsten; Hill, Paul B.

    2005-01-01

    "Der vorliegende Beitrag untersucht die Auswirkungen von Konflikten auf die wahrgenommene Stabilität von Partnerschaften. Besonderes Augenmerk wird dabei auf die vermittelnde Rolle von Paarinteraktion und Partnerschaftszufriedenheit gelegt. Weiterhin werden Wechselwirkungen zwischen Konflikten und Paarinteraktionen und deren Folgen für den Partnerschaftserfolg betrachtet. Die Kernthese lautet dabei, dass Konflikte Partnerschaften weniger stark beeinträchtigen, wenn ausreichend 'positive' bzw....

  18. Verbraucher und grüne Gentechnik: Mechanismen der Ablehnung und ihre Änderungsresistenz

    DEFF Research Database (Denmark)

    Scholderer, Joachim

    In den Jahren 2001 und 2002 hat das Bundesministerium für Verbraucherschutz, Ernährung und Landwirtschaft ein Diskursprojekt zur grünen Gentechnik durchgeführt. Das Projekt brachte politische Akteure, Vertreter gesellschaftlicher Interessengruppen und wissenschaftliche Experten in Workshops...

  19. In vitro-Permeationsstudien von hydrophilen und lipophilen Arzneistoffen an okularen Geweben und Zellkulturen

    OpenAIRE

    Scholz, Martina

    2003-01-01

    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...

  20. Finanzkrise, Sozialkrise und ungleiche Entwicklung in Südkorea und Thailand

    DEFF Research Database (Denmark)

    Schmidt, Johannes Dragsbæk

    2008-01-01

    ?   Welche Bedeutung haben Finanzmärkte im Entwicklungsprozess und wie können diese "entwicklungsfreundlich" gestaltet werden?   Diesen Fragen gehen die AutorInnen und Autoren unter anderem anhand von Länderbeispielen nach. Die analysierten Regionen und Länder umfassen Südostasien (Südkorea, Malaysia...

  1. Relationship between the MDS-UPDRS and Quality of Life: A large multicenter study of 3206 patients.

    Science.gov (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

    2018-03-28

    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.

  2. Relationship between the MDS-UPDRS domains and the health-related quality of life of Parkinson's disease patients.

    Science.gov (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

    2014-03-01

    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.

  3. Therapeut-Klient-Interaktion: Einstellungen und Interventionen

    OpenAIRE

    Mallin, Uwe

    2010-01-01

    Die vorliegende Arbeit befasst sich mit TherapeutenInterventionen aus der Sicht von Klienten und vom Therapeuten selbst erhobenen Ersteindrücken. Diesem Forschungsinteresse dient eine synoptische Betrachtungsweise ausgewählter Aspekte der Psychotherapie-Prozessforschung im Rahmen des Allgemeinen Psychotherapiemodells von Orlinsky und Howard. Konzeptionell werden Einschätzungen des Therapeuten durch seine Klienten per Fragebögen, eine Selbsteinschätzung des Therapeuten per Fragenkatalog und we...

  4. Frauen und Arbeit : der Fähigkeitenansatz

    OpenAIRE

    Nussbaum, Martha C.

    2003-01-01

    "Nussbaum entwickelt in diesem Artikel ihre Version des Fähigkeitenansatzes. Ausgehend von den Lebensgeschichten zweier indischer Frauen zeigt sie, wie verschiedene normative Konzepte die Veränderungen im Leben dieser Frauen bewerten. Sie benennt die Schwierigkeiten, die jeder interkulturelle Bewertungsrahmen meistern muss, kritisiert die dominierenden ökonomischen Ansätze, wie Pro-Kopf-Einkommen und Präferenzbefriedigung, und begründet, warum ein mit den grundlegenden Rechten und Freiheiten ...

  5. Von Medien, Übertragungen und Automaten

    Directory of Open Access Journals (Sweden)

    Alessandro Barberi

    2013-12-01

    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.

  6. Verletzungen und Fehlbeanspruchungen im leistungsorientierten Rudersport

    OpenAIRE

    Bussian, Marc Robert

    2004-01-01

    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...

  7. Zeitschriftenübersicht und Buchbesprechungen

    OpenAIRE

    1994-01-01

    Zeitschriftenübersicht und Buchbesprechungen: Grosskurth P. (1993): Melanie Klein - ihre Welt und ihr Werk. Stuttgart. Deegener, G. /Dietel, B. /Kassel, H. /Matthaei, R. /Nodl, H. (1992) Neuropsychologische Diagnostik bei Kindern und Jugendlichen. Weinheim. Buchholz, M. B. (1993): Dreiecksgeschichten. Eine klinische Theorie psychoanalytischer Familientherapie. Gottingen. Heinl, P. (1994)- Maikäfer flieg, dein Vater ist im Krieg ... Seelische Wunden aus der Kriegskindheit. Münc...

  8. Gestaltung zeit- und sicherheitskritischer Warnungen im Fahrzeug

    OpenAIRE

    Fricke, Nicola

    2009-01-01

    Heutige Fahrzeuge beinhalten eine Reihe technischer Unterstützungsangebote, die dem Fahrer bei der Ausführung seiner Fahraufgabe und weiteren Nebentätigkeiten assistieren. In der Interaktion mit diesen Systemen können jedoch erhebliche Probleme auftreten, vor allem im Zusammenspiel der verschiedenen Funktionen. Besonders für zeit- und sicherheitskritische Information, wie z. B. bei Kollisionswarnungen, ist es unbedingt erforderlich, dass derartige Meldungen informativ, aber auch einfach und s...

  9. 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.

    Science.gov (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

    2017-10-01

    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.

  10. Schilddrüse und Schwangerschaft

    Directory of Open Access Journals (Sweden)

    Zettinig G

    2009-01-01

    Full Text Available Kinderwunsch, Schwangerschaft und die Zeit nach einer Geburt sind besondere Lebensabschnitte bei Patientinnen mit Schilddrüsenerkrankungen. Bei jungen Frauen sind Autoimmunerkrankungen der Schilddrüse, die Einfluss auf die Fruchtbarkeit und die intellektuelle und körperliche Entwicklung des Fetus haben können, häufig. Schilddrüsenerkrankungen können sich in dieser Lebensphase auch erstmals manifestieren; besondere Beachtung verdient die Wechselwirkung von β-HCG mit dem TSH-Rezeptor. Diese Übersicht behandelt das aktuelle Management von Patientinnen mit Schilddrüsenerkrankungen bei Kinderwunsch, in der Schwangerschaft und Postpartalperiode.

  11. Cognitive distortions based on MDS configuration and sketch mapping: a case study in Beijing

    Science.gov (United States)

    Shen, Si; Xue, Lulu; Wu, Lun; Liu, Yu

    2007-06-01

    As an emerging field, cognitive map kept playing a significant role in geography these decades. To date, there are two dominant methods to externalize human's internal cognitive map, namely, multidimensional scaling (MDS) and skech mapping. However, among most recent researches on cognitive map, the differences between both methods are always ignored. The usage of one method over another is still under scrutiny. In order to shed light on the similarity or distinctions of MDS configuration and sketch mapping, we conducted an experiment on Beijing residents by requesting a sketch of the region within 3rd Ring and meanwhile extracting distance estimates between 8 landmarks. Employing the Bidimensional regression along with standard deviational ellipse, we studied the global and local distortions among two kinds of cognitive maps and quantitatively measure the overall and local cognitive maps distortions. Besides, we use Monte Carlo simulation method to calculate the radius of distortion for the Distortion Index (DI). It shows that the average cognitive distortion of habitants in Beijing is 2km to 3km, and the distortion takes 2nd-ring road as a border, displaying a southwest-northeast diagonal stretch and an east-west contracted tendency. The distortion in the two methods is remarkably both correlated with factors, such as travel frequency and years of residence. Comparing two methods, it turned out that sketch map was more consistent with real map, while the distortion orientations of sketch map resembled MDS configuration. Finally, we gave possible reasons with regard to above conclusions and advices for future usage of two methods.

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

    KAUST Repository

    Darwish, Manar M

    2013-05-01

    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).

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

    Directory of Open Access Journals (Sweden)

    M. Slanina

    2004-12-01

    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.

  14. Städtische Diskurse um Migration im Wandel. Integration, diversity und soziale Bewegungen in München und Berlin

    Directory of Open Access Journals (Sweden)

    Natalie Bayer

    2014-12-01

    Full Text Available Sowohl im Kontext der kommunalen Integrationspolitik als auch in der Stadtplanung, der Repräsentationspolitik und der regionalen Standort- und Wirtschaftspolitik ist das Thema ,Migration in den Städten‘ wieder auf die politische Agenda gesetzt worden. Doch der Gegenstand, die theoretischen Konzeptualisierungen und die Perspektivierungen sind oft uneindeutig und politisch umkämpft. Gerade auf stadtpolitischer Ebene haben sich zudem starke migrantische Organisationen und Proteste formiert, die oftmals in neuen Allianzen agieren und sich hegemonialen Vorstellungen von ,Integration‘ und ,sozialer Mischung‘ verweigern. Ein Fachgespräch zwischen Natalie Bayer, Andrej Holm und Henrik Lebuhn über städtische Migrationspolitiken in München und Berlin sowie über Fragen und Probleme, die sich auf diesem Feld an der Schnittstelle zwischen kritischer Wissenschaft und praktischer Politik ergeben.

  15. Editorial 01/2013 Normen und Normierungen

    Directory of Open Access Journals (Sweden)

    Christian Swertz

    2013-03-01

    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

  16. 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

    2017-01-01

    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.

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

    Science.gov (United States)

    Li, Qiang; Gu, Yu; Jia, Jing

    2017-01-30

    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.

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

    Science.gov (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.

    2013-01-01

    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

  19. Results of allogeneic stem cell transplantation in the Spanish MDS registry: prognostic factors for low risk patients.

    Science.gov (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

    2014-10-01

    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.

  20. Steueroasen und Regulierungsoasen – Auswirkungen auf die Stabilität des Finanzmarkts und politische Implikationen

    Directory of Open Access Journals (Sweden)

    Michaela Schmidt

    2012-12-01

    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.

  1. [15-year results following implantation of a stem type AML hip prosthesis].

    Science.gov (United States)

    Schwerter, K; Meyenberg, A; Sander, K; Layher, F; Roth, A

    2013-06-01

    The trend in arthroplasty of the hip joint to implement new models is partly based on theoretical considerations. In order to verify to which extent the philosophy of individual models is ultimately successful, the presentation of long-term results is required. In the years 1991 and 1992, 433 patients with primary implantation of an uncemented total hip replacement in primary coxarthrosis with a stem type AML (anatomic medullary locking) were treated surgically. 283 of them got a cementless cup type Duraloc. In 311 (71.8 %) patients the mean survival rate of the prosthesis could be determined at a mean follow-up of 15.5 years. 145 (33.5 %) patients were followed up completely both clinically and radiologically. Radiographically, the stem position, changes of the periprosthetic bone of the stem and the cup, as well as the wear of the cups were examined. The cumulative survival rate of the AML stem after 15.5 years was 97.5 %, of the Duraloc cup 88.2 %. The clinical results of the hip scores according to Harris and Merle d'Aubigné were good and excellent and patient satisfaction was very high. There was no relationship between stem position, stress shielding and surrounding lyses at the femur and the acetabulum and survival of stem or cup. There was no correlation between inlay wear and survival of the Duraloc cup. A subsiding of the stem in 2 cases had no effect on the clinical symptoms and quality of life. The press-fit implanted AML stem and the Duraloc cup revealed very good results during the investigation period. Like other implants, the survival rate is limited at the presented implant mainly by the cup. Georg Thieme Verlag KG Stuttgart · New York.

  2. MRD in AML: does it already guide therapy decision-making?

    Science.gov (United States)

    Ossenkoppele, Gert; Schuurhuis, Gerrit Jan

    2016-12-02

    Prognostic factors determined at diagnosis are predictive for outcome whereas achievement of morphological complete remission (CR) is still an important end point during treatment. Residual disease after therapy may reflect the sum of all diagnosis and postdiagnosis resistance mechanisms/factors; its measurement could hypothetically be very instrumental for guiding treatment. The possibility of defining residual disease (minimal residual disease [MRD]) far below the level of 5% blast cells is changing the landscape of risk classification. In this manuscript, the various methods, all different in sensitivity, specificity, and phase of development, to assess MRD are discussed. Currently, the 2 methods mostly used are flow cytometry-based immune MRD (multiparameter flow cytometry [MPFC]) and molecular MRD assessed by real-time quantitative polymerase chain reaction. Both have advantages and disadvantages that are summarized in detail. Many studies in children as well as adults already demonstrated that MRD detection by MPFC or molecular MRD provides strong prognostic information in acute myeloid leukemia (AML) after both induction and consolidation. These studies are summarized in this review. The general conclusion of this review is that a better definition of disease burden than morphological CR is now emerging. MRD assessed by flow or molecular techniques should become standard in every clinical trial in AML. Harmonization of antibody panels, introduction of single-cell tube systems (for determination of residual leukemic stem cells), and standardized analytical programs will pave the way for individual risk assessment and become a surrogate end point for survival in studies investigating new drugs, hopefully resulting in faster drug approval in AML. © 2016 by The American Society of Hematology. All rights reserved.

  3. Monitoring response and resistance to the novel arsenical darinaparsin in an AML patient

    Directory of Open Access Journals (Sweden)

    Torsten Holm eNielsen

    2013-02-01

    Full Text Available Acute myeloid leukemia (AML with inversion of chromosome 3 is characterized by overexpression of EVI1 and carries a dismal prognosis. Arsenic-containing compounds have been described to be efficacious in malignancies overexpressing EVI1. Here we describe a case of AML with inv(3(q21q26.2 treated with the organic arsenical darinaparsin. Using a personalized medicine approach, different arsenicals were screened for anti-leukemic effect against the patient’s cells ex vivo. The most promising compound, darinaparsin, was selected for in vivo treatment. Clinical effect was almost immediate, with a normalization of temperature, a stabilization of white blood cell (WBC counts and an increased quality of life. Longitudinal monitoring of patient response and resistance incorporating significant correlative studies on patient derived blood samples over the two cycles of darinaparsin given to this patient allowed us to evaluate potential mechanisms of response and resistance. The anti-leukemic effects of darinaparsin correlated with inhibition of the alternative NF-κB pathway and production of the inflammatory cytokine IL-8. Emergence of resistance was suspected during treatment cycle 2 and supported by xenograft studies in nude mice. Darinaparsin resistance correlated with an attenuation of the effect of treatment on the alternative NF-κB pathway. The results from this patient indicate that darinaparsin may be a good treatment option for inv(3 AML and that inhibition of the alternative NF-κB pathway may be predictive of response. Longitudinal monitoring of disease response as well as several correlative parameters allowed for the generation of novel correlations and predictors of response to experimental therapy in a heavily pretreated patient.

  4. Allelic methylation levels of the noncoding VTRNA2-1 located on chromosome 5q31.1 predict outcome in AML

    DEFF Research Database (Denmark)

    Treppendahl, Marianne Bach; Qiu, Xiangning; Søgaard, Alexandra

    2012-01-01

    -regulate the phosphorylated RNA-dependent protein kinase (pPKR), whose activity has been shown to be modulated by vtRNA2-1. Because pPKR promotes cell survival in AML, the data are consistent with vtRNA2-1 being a tumor suppressor in AML. This is the first study to show that vtRNA2-1 might play a significant role in AML......, that it is either mono- or biallelically expressed in the blood cells of healthy individuals, and that its methylation state predicts outcome in AML....

  5. Esculetin Downregulates the Expression of AML1-ETO and C-Kit in Kasumi-1 Cell Line by Decreasing Half-Life of mRNA

    Directory of Open Access Journals (Sweden)

    Sharad Sawney

    2015-01-01

    Full Text Available One of the most frequent genetic aberrations in acute myeloid leukemia (AML is chromosomal translocation between AML1/RUNX1 on chromosome 21 and ETO gene on chromosome 8 resulting in the expression of chimeric oncogene AML1-ETO. Although patients with t(8;21 translocation have good prognosis, 5-year survival is observed only in 50% of the cases. AML1-ETO translocation is usually accompanied by overexpression of mutant C-Kit, a tyrosine kinase, which contributes to uncontrolled proliferation of premature blood cells leading to relapse and poor prognosis. We illustrate the potential use of esculetin on leukemic cell line, Kasumi-1, bearing t(8;21 translocation and mutated C-Kit gene. Esculetin decreases the expression of AML1-ETO at both protein and transcript level within 24 hours of treatment. Half-life of AML1-ETO mRNA was reduced from 7 hours to 1.5 hours. Similarly half-life of C-Kit mRNA was reduced to 2 hours from 5 hours in esculetin treated cells. Esculetin also perturbed the expression of ectopically expressed AML1-ETO in U937 cells. The decreased expression of AML1-ETO chimeric gene was associated with increased expression of LAT1 and RUNX3 genes, targets of AML1. We envisage that discovery of a drug candidate which could target both these mutated genes would be a considerable breakthrough for future application.

  6. Die Elementarkonstanten und die Mathematik

    Science.gov (United States)

    Rompe, Robert; Treder, Hans-Jürgen

    Die Elementarkonstanten im Sinne von Max Planck sind von ähnlicher Bedeutung wie die reinen Zahlen der Mathematik. Die Newtonschen Prinzipien und die Elementarkonstanten zusammen sind der Grundbau der physikalischen Theoriebildung.Translated AbstractThe Elementary Constants and the MathematicThe elementary constants in the sense of Max Planck are of analogous meaning as the pure numbers in mathematics. The Newtonian principles together with the elementary constants are the basis for creating physical theories.

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

    International Nuclear Information System (INIS)

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

    1999-01-01

    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

  8. 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

    2017-01-01

    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.

  9. YKL-40 in allogeneic hematopoietic cell transplantation after AML and myelodysplastic syndrome

    DEFF Research Database (Denmark)

    Kornblit, Brian; Wang, T; Lee, S J

    2016-01-01

    recipient and donor plasma YKL-40 concentrations in patients with AML (n=624) or myelodysplastic syndrome (n=157) treated with allogeneic hematopoietic cell transplantation (HCT). In recipients, the plasma YKL-40 concentrations were increased when the HCT-comorbidity index was ⩾5 (P=0.028). There were...... no significant associations between plasma YKL-40 concentrations in recipients and any outcome measures. In donors with YKL-40 plasma concentrations above the age-adjusted 95th percentile, a trend toward increased grade II-IV acute GvHD in recipients was observed (adjusted hazard ratio 1.39 (95% confidence...

  10. ETO, but not leukemogenic fusion protein AML1/ETO, augments RBP-Jkappa/SHARP-mediated repression of notch target genes.

    Science.gov (United States)

    Salat, Daniela; Liefke, Robert; Wiedenmann, Jörg; Borggrefe, Tilman; Oswald, Franz

    2008-05-01

    Notch is a transmembrane receptor that determines cell fates and pattern formation in all animal species. After specific ligand binding, the intracellular part of Notch is cleaved off and translocates to the nucleus, where it targets the DNA binding protein RBP-Jkappa. In the absence of Notch, RBP-Jkappa represses Notch target genes by recruiting a corepressor complex. We and others have previously identified SHARP as one component of this complex. Here, we show that the corepressor ETO as well as the leukemogenic fusion protein AML1/ETO directly interacts with SHARP, that ETO is part of the endogenous RBP-Jkappa-containing corepressor complex, and that ETO is found at Notch target gene promoters. In functional assays, corepressor ETO, but not AML1/ETO, augments SHARP-mediated repression in an histone deacetylase-dependent manner. Furthermore, either the knockdown of ETO or the overexpression of AML1/ETO activates Notch target genes. Therefore, we propose that AML1/ETO can disturb the normal, repressive function of ETO at Notch target genes. This activating (or derepressing) effect of AML1/ETO may contribute to its oncogenic potential in myeloid leukemia.

  11. Erfahrungen an der Schnittstelle von Medienarbeit und Praxisforschung

    Directory of Open Access Journals (Sweden)

    Peter Holzwarth

    2007-11-01

    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.

  12. Leitung und Kooperation in wissenschaftlichen Bibliotheken Berlins - eine empirische Untersuchung

    OpenAIRE

    Paul, Gerhard

    1998-01-01

    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...

  13. [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

    2012-01-01

    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)

  14. On Orbit Osteobiology Experiments: from "STROMA" to "MDS" -from in vitro to in vivo

    Science.gov (United States)

    Liu, Yi; Cancedda, Ranieri

    Spaceflight causes profound changes in the skeleton, in particular, in the weight-loading bones. Uncoupling of bone remodeling equilibrium between bone formation and resorption is con-sidered responsible for the microgravity-induced bone loss. These changes result in weak-ened and brittle bones prone to fracture on re-entry and in accelerated osteoporosis, making bone deterioration a major problem obstructing the prospects of long-duration manned space flight. Osteoblasts (bone forming cells) and osteocytes (bone resorption cells) are known to be mechano-sensors. Short-exposure of osteoblasts to simulated microgravity ensnarled cell adhe-sion and cytoskeleton. Also osteoblast precursors such as bone marrow stroma cells (BMSC) were shown to be sensitive to mechanical loading. We performed a series of STROMA space-flight experiments by culturing BMSC or co-culturing osteoblasts and osteoclast precursors in automated bioreactors on orbit. Genechip analysis revealed an inhibition of cell proliferation and an unexpected activation of nervous system development genes by spaceflight. To unravel effects of microgravity on genes governing bone mass, transgenic mice with a higher bone mass were flown to orbit inside the Mice Drawer System (MDS) payload. The MDS experiment was launched inside Shuttle Discovery in STS-128 on August 28 2009 at 23:58 EST, and returned to earth by Shuttle Atlantis in STS129 on November 27 2009 at 9:47 EST, marking it as the first long duration animal experiment on the International Space Station (ISS).

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

    Directory of Open Access Journals (Sweden)

    Saswati Mukherjee

    2016-01-01

    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.

  16. Prognostic impact of a suboptimal number of analyzed metaphases in normal karyotype lower-risk MDS.

    Science.gov (United States)

    de Swart, Louise; Smith, Alex; Haase, Detlef; Fenaux, Pierre; Symeonidis, Argiris; Cermak, Jaroslav; Sanz, Guillermo; Stauder, Reinhard; Mittelman, Moshe; Hellström-Lindberg, Eva; Malcovati, Luca; Langemeijer, Saskia; Skov-Holm, Mette; Mądry, Krzysztof; Germing, Ulrich; Almeida, Antonio Medina; Tatic, Aurelia; Savic, Aleksandar; Šimec, Njetočka Gredelj; van Marrewijk, Corine; Guerci-Bresler, Agnes; Sanhes, Laurence; Luño, Elisa; Culligan, Dominic; Beyne-Rauzy, Odile; Burgstaller, Sonja; Blijlevens, Nicole; Bowen, David; de Witte, Theo

    2018-04-01

    Conventional karyotype is one of the most relevant prognostic factors in MDS. However, about 50% of patients with MDS have a normal karyotype. Usually, 20-25 normal metaphases (nMP) are considered to be optimal to exclude small abnormal clones which might be associated with poor prognosis. This study evaluated the impact of examining a suboptimal number of metaphases in patients recruited to the EUMDS Registry with low and intermediate-1 risk according to IPSS. Only 179/1049 (17%) of patients with a normal karyotype had a suboptimal number of nMP, defined as less than 20 metaphases analyzed. The outcome (overall survival and progression-free survival) of patients with suboptimal nMP was not inferior to those with higher numbers of analyzed MP both in univariate and multivariate analyses. For patients with an abnormal karyotype, 224/649 (35%) had a suboptimal number of MP assessed, but this did not impact on outcome. For patients with a normal karyotype and suboptimal numbers of analyzable metaphases standard evaluation might be acceptable for general practice, but we recommend additional FISH-analyses or molecular techniques, especially in candidates for intensive interventions. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

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

    Science.gov (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.

    2014-01-01

    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

  18. Vorberufliche und berufliche Bildung im internationalen Vergleich

    OpenAIRE

    Lauterbach, Uwe

    1987-01-01

    Dieser Artikel behandelt die Themen: Übergang vom Schul- in das Ausbildungs- und Beschäftigungssystem, Vorberufliche Bildung in der Sekundarschule, Berufliche Erstausbildung in den Sekundarschulen in alternierender Form oder durch die Wirtschaft, Typisierung der vorberuflichen und beruflichen Bildung im internationalen Vergleich. (DIPF/Orig.)

  19. Germanistikstudium in Marokko – Probleme und Perspektiven

    African Journals Online (AJOL)

    Gesellschaftliche Veränderungen und die schlechte Lage der Bildung in Marokko machten es dringend erforderlich .... sodass unsere Studierenden des Faches Germanistik von den beruflichen Chancen profitieren können, die ... der deutschen Sprache und verschaffen sich Vorteile im beruflichen Auftreten. Insbesondere.

  20. Die Gestalten und das Gestalten der Welt

    NARCIS (Netherlands)

    Ierna, Carlo; Höfer, Ulf; Valent, Juta

    2017-01-01

    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

  1. Systeme im Einsatz. Lernmanagement, Kompetenzmanagement und PLE

    NARCIS (Netherlands)

    Kalz, Marco; Schön, Sandra; Lindner, Martin; Roth, Detlev; Baumgartner, Peter

    2011-01-01

    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

  2. Nachhaltiger Lebensmittelkonsum gestern, heute und morgen

    DEFF Research Database (Denmark)

    Aschemann-Witzel, Jessica

    2013-01-01

    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...

  3. Sprachenpolitik in Europa – Tatsachen und Perspektiven

    African Journals Online (AJOL)

    der Bilder vom jeweils Anderen auch tatsächlich gedeckt. Nach wie vor gibt es massive. Spannungen, die nur mühsam pazifiziert sind und die .... Westfalen), Staaten wie Dänemark, Schweden oder Finnland (Bayern, Hessen, Sachsen), bis hin zu dem kleinsten EU-Mitglied Luxemburg (Saarland, Freie und Hansestadt ...

  4. Zur Struktur und Funktion von Synonymen

    Directory of Open Access Journals (Sweden)

    Marina Zorman

    1998-12-01

    Full Text Available Der Artikel behandelt die Synonyme im Licht der funktionell-strukturellen Sprachtheorie Coserius. 1 Die Wahl der theoretischen Grundsätze wurde durch die Festellung diktiert, daß die bisherigen Erkenntnisse über die Synonymie widersprüchlich sind und daß auch schon über alle Feststellungen berechtigte Einsprüche erhoben wurden. Deshalb wird in dieser Arbeit auf der genannten theoretischen Grundlage, die verschiedene Gesichtspunkte des Problems verbindet, anstatt sie zu trennen (s. Punkt 2, ein Modell für die Analyse von Synonymen vorgestellt (3, das die klassischen Schwächen der Semantikforschung (zu geringe Menge tatsächlicher Daten, Subjektivität und Introspektion durch eine empirische Untersuchung in einem Textkorpus zu ersetzen versucht. In die Analyse sind drei Inhaltsebenen einbezogen (Bezeichnung, Bedeutung und Sinn und ihnen sind jeweils entsprechende Untersuchungsmethoden zugeordnet. Im Sinne des Modells wurden in der Arbeit Zorman 1997 zwei slowenische Synonympaare (kuverta - ovojnica und borba - boj analysiert, die als Beispiele reiner (und totaler Synonymie gelten können. Die Analyse wird aus Platzgründen an dieser Stelle nicht detailliert dargestellt,2 veranschaulicht werden nur ihre Tragweite und die Ergebnisse (4. Im letzten Teil (5 werden die Leistungen der vorgeschlagenen Methode bewertet und einige Annahmen dargestellt, die der weiteren Erforschung der Synonyme dienen könnten. Die objektive Behandlung der Synonymie unter unterschiedlichen Gesichtspunkten scheint einige Dogmen über Synonyme in Frage zu  stellen.

  5. Über Sturzmelder und andere Pflegeroboter

    OpenAIRE

    Wolff, Eberhard

    2013-01-01

    Falls Sie nicht wissen, was ein «Hubot» ist, empfiehlt sich die Lektüre dieses Beitrags ganz besonderes. Denn er kann unheimlich hilfreich sein: für Opi Tee und Spaghetti kochen oder ihn bei Bedarf reanimieren. Äusserst vielseitig also. Wie Mensch und Technik interagieren, untersuchte ein Tagung an der Universität Fribourg.

  6. Schaulust und Horror Soziokulturelle - Perspektiven auf PEEPING TOM

    Directory of Open Access Journals (Sweden)

    Thomas Ballhausen

    2010-09-01

    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.

  7. A 78-year-old man with acute myeloid leukemia (AML) and acute renal failure.

    Science.gov (United States)

    Tapper, Elliot B; Luptakova, Katarina; Joyce, Robin M; Tzachanis, Dimitrios

    2014-08-30

    Male, 78. Acute myeloid leukemia (AML). Dyspnea • fatigue. Idarubicin followed by cytarabine. Chemotherapy. Hematology. Unusual clinical course. Renal failure is a common presentation of acute myelomonocytic and monocytic leukemia. It is usually the result of a combined glomerular and tubular dysfunction and is associated with a poor prognosis. No guidelines exist for treatment. We herein describe the case of a 78-year-old Caucasian man who presented with acute myeloid leukemia M5, leukostasis with a white count of 340 000/ml, and acute renal failure with a creatinine of 7.7/dL. The patient was initially treated with leukapheresis and 3 days of idarubicin in the setting of continuous renal replacement therapy that resulted in rapid reversal of his renal failure. He then received 7 days of continuous infusion cytarabine and went into a complete remission. Renal failure may complicate the presentation of AML but can be reversible with treatment. Dose adjustment of the chemotherapy is not needed and the treatment can be greatly facilitated with the use of continuous renal replacement therapy, as indicated in our case report. In addition, we emphasize that organ dysfunction, even in elderly patients, is not necessarily a contraindication to aggressive treatment if it is felt to be disease-related and reversible.

  8. Wirtschaftlichkeit von Facility Management - Entwicklungen und Trends

    Directory of Open Access Journals (Sweden)

    Redlein, Alexander

    2018-01-01

    Full Text Available Das vorliegende Paper baut auf den jährlichen Umfragen bzw. Studien des Immobilien und Facility Management (IFM der Technischen Universität Wien (TU Wien und der Dissertation von Susanne Hauk aus dem Jahr 2007 auf. Neben der Darstellung allgemeiner Daten konzentriert sich die Arbeit im Wesentlichen auf folgende Forschungsfragen:  In welchen Bereichen können Einsparungen generiert werden?  In welchen Bereichen können Produktivitätssteigerungen lukriert werden?  Mit welchen Problemen/Kostentreibern sind Facility Manager bzw. FM-Abteilungen konfrontiert?  Welche (statistisch signifikanten Zusammenhänge bestehen zwischen verschiedenen Merkmalen/Variablen? Seit dem Jahr 2005 wurden jährlich FM-Verantwortliche von den 500 größten Unternehmen Österreichs befragt. Im Rahmen der Umfrage sollen wissenschaftlich fundiert die obigen Forschungsfragen geklärt werden. Als Werkzeuge für die Datenerhebung wurden das Telefon und/oder elektronische Wege gewählt. Die Umfrage wurde anhand eines standardisierten Fragebogens mit 36 Fragen zu den verschiedensten FM-Bereichen durchgeführt. Im Rahmen der vorliegenden Arbeit sollen die Ergebnisse der aktuellen Umfrage dargestellt und mit den Ergebnissen der Studien der letzten Jahre verglichen werden. Die vorliegende Arbeit beschäftigt sich vor allem mit jenem Teil der Umfrage, der die oben genannten Forschungsfragen behandelt. Ziel ist dabei, die wichtigsten Parameter und Einflussfaktoren in den Bereichen Einsparungen, Produktivitätssteigerungen und Kostentreiber zu identifizieren und die Entwicklungen und Trends näher darzustellen. Dabei zeigt sich, dass effizientes FM große Potentiale in den Bereichen Einsparungen und Produktivitätssteigerungen lukrieren kann. Auch wenn die Einführung von FM zu Beginn mit Kosten/Problemen verbunden ist, so kann dies durch spätere Einsparungen und Produktivitätssteigerungen kompensiert werden.

  9. Bewegung bei Vorschulkindern: Empfehlungen und Wirklichkeit

    Directory of Open Access Journals (Sweden)

    Graf C

    2011-01-01

    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.

  10. New insights into transcriptional and leukemogenic mechanisms of AML1-ETO and E2A fusion proteins.

    Science.gov (United States)

    Li, Jian; Guo, Chun; Steinauer, Nickolas; Zhang, Jinsong

    2016-08-01

    Nearly 15% of acute myeloid leukemia (AML) cases are caused by aberrant expression of AML1-ETO, a fusion protein generated by the t(8;21) chromosomal translocation. Since its discovery, AML1-ETO has served as a prototype to understand how leukemia fusion proteins deregulate transcription to promote leukemogenesis. Another leukemia fusion protein, E2A-Pbx1, generated by the t(1;19) translocation, is involved in acute lymphoblastic leukemias (ALLs). While AML1-ETO and E2A-Pbx1 are structurally unrelated fusion proteins, we have recently shown that a common axis, the ETO/E-protein interaction, is involved in the regulation of both fusion proteins, underscoring the importance of studying protein-protein interactions in elucidating the mechanisms of leukemia fusion proteins. In this review, we aim to summarize these new developments while also providing a historic overview of the related early studies. A total of 218 publications were reviewed in this article, a majority of which were published after 2004.We also downloaded 3D structures of AML1-ETO domains from Protein Data Bank and provided a systematic summary of their structures. By reviewing the literature, we summarized early and recent findings on AML1-ETO, including its protein-protein interactions, transcriptional and leukemogenic mechanisms, as well as the recently reported involvement of ETO family corepressors in regulating the function of E2A-Pbx1. While the recent development in genomic and structural studies has clearly demonstrated that the fusion proteins function by directly regulating transcription, a further understanding of the underlying mechanisms, including crosstalk with other transcription factors and cofactors, and the protein-protein interactions in the context of native proteins, may be necessary for the development of highly targeted drugs for leukemia therapy.

  11. An AML1-ETO/miR-29b-1 regulatory circuit modulates phenotypic properties of acute myeloid leukemia cells.

    Science.gov (United States)

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

    2017-06-20

    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.

  12. 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)

    2012-01-01

    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

  13. 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.

    2008-01-01

    (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...

  14. Sowjetunion und Völkerrecht 1962-1973 / Henn-Jüri Uibopuu

    Index Scriptorium Estoniae

    Uibopuu, Henn-Jüri, 1929-2012

    1980-01-01

    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

  15. Nachweis und Differenzierung von Campylobacter jejuni, C. coli und C. lari in Lebensmitteln mittels Quadruplex real-time PCR

    OpenAIRE

    Mayr, Anja Maria

    2009-01-01

    Es wurde ein Quadruplex real-time PCR-Verfahren zum parallelen Nachweis und zur Differenzierung der lebensmittelrelevanten thermophilen Campylobacter spp. Campylobacter jejuni, Campylobacter coli und Campylobacter lari in Geflügel, Fleisch, Fisch und Muscheln etabliert. Das Nachweissystem wurde hinsichtlich seiner Selektivität, Sensitivität, Effizienz, Präzision und Robustheit überprüft und im Vergleich zur konventionellen Diagnostik (kultureller Nachweis) anhand von 464 Feldproben validiert....

  16. 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.

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

    Science.gov (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.

    2018-01-01

    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.

  18. Zur Diagnose von isolierten und kombinierten Leseproblemen: Definitionen, Operationalisierungen und Vorkommenshäufigkeiten

    OpenAIRE

    Valtin, Renate; Voss, Andreas; Bos, Wilfried

    2015-01-01

    Aufgrund einer Vielzahl von Definitionen und Operationalisierungen gibt es keine verlässlichen Zahlen über die Vorkommenshäufigkeiten isolierter oder kombinierter Leseprobleme, auch bedingt durch das Fehlen repräsentativer Studien. Anhand des für Deutschland repräsentativen Datensatzes von IGLU und TIMSS 2011 wurde die Vorkommenshäufigkeit von isolierten und kombinierten Leseproblemen in kompetenzorientierten Tests bestimmt. Insgesamt weisen die Ergebnisse darauf hin, dass Leseprobleme selten...

  19. Patente in Europa und der Triade - Strukturen und deren Veränderung

    OpenAIRE

    Frietsch, R.

    2007-01-01

    Nr. 9-2007 vom Fraunhofer-Institut für Systemtechnik und Innovationsforschung: Der Bericht erweitert und aktualisiert frühere Ausarbeitungen dieser Serie. Es werden Triade-Patente, Patentanmeldungen im Bereich der Hochtechnologie sowie internationale Technologie-Kooperationen (Ko-Patente) untersucht. Einer methodischen Diskussion der Patente als Innovationsindikator und dessen Interpretation schließen sich empirische Ergebnisse für die einzelnen Patentdaten an. Ein weiterer Teil befasst sich ...

  20. Kolluvien und Auensedimente als Geoarchive im Umfeld der historischen Hammerwerke Leidersdorf und Wolfsbach (Vils/Opf.)

    OpenAIRE

    Beckmann, Sabine

    2008-01-01

    Die vorliegende Studie leistet einen Beitrag zur Erfassung der bergbaubedingten Folgen auf die Landschaft der Oberpfalz. Der ostbayerische Raum besitzt eine jahrhundertelange Tradition im Abbau und der Verarbeitung von Erzen. Südlich von Amberg wurden an der Vils zahlreiche Hammerwerke zur Verhüttung und Verarbeitung von Eisenerz errichtet. Dies ist verbunden mit flussbaulichen Maßnahmen und Stoffeinträgen in die Aue. Hauptziel der Arbeit ist es, die anthropogene Beeinflussung der Sedimente d...

  1. Modellierung und Simulation der Dynamik und des Kontakts von Reifenprofilblöcken

    OpenAIRE

    Moldenhauer, Patrick

    2010-01-01

    Die Kontaktverhältnisse zwischen Reifen und Fahrbahn bestimmen die maximal übertragbaren Beschleunigungs-, Brems- und Seitenkräfte des Fahrzeugs und sind daher für die Fahrsicherheit von großer Bedeutung. In dieser Arbeit wird ein Modell zur numerisch effizienten Simulation der hochfrequenten Dynamik einzelner Reifenprofilblöcke entwickelt. Der vorgestellte Modellansatz nutzt einerseits die Vorteile der Finite-Elemente-Methode, welche die Bauteilstruktur detailliert auflösen kann, bei der je...

  2. Bakteriochlorophyllvorstufen und Pigment-Protein-Komplexe in Rhodospirillum rubrum ST3 und GN11

    OpenAIRE

    Hammel, Jörg U.

    2006-01-01

    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...

  3. 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

    2014-01-01

    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......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...... after Aza+Epo, giving a total response rate of 20%. Mutational screening revealed a high frequency of recurrent mutations. Although no single mutation predicted for response, SF3A1 (n=3) and DNMT3A (n=4) were only observed in non-responders. We conclude that Aza can induce TI in severely anemic MDS...... 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....

  4. 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

    2016-01-01

    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...

  5. Wheat Mds-1 encodes a heat-shock protein and governs susceptibility towards the Hessian fly gall midge

    Science.gov (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...

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

    Science.gov (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

    2017-04-01

    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.

  7. 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

    2016-01-01

    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...... to the generation of tumor-specific neoepitopes....

  8. Die Kunst des Intavolierens: Gebundenheit und Freiheit

    Directory of Open Access Journals (Sweden)

    Ring, Johannes

    2003-12-01

    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

  9. 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

    2014-01-01

    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...... of Pediatric Hematology and Oncology (NOPHO). METHODS: A population-based cohort of children treated for AML according to the NOPHO-AML-84, -88, and -93 trials included 138 eligible survivors of whom 102 (74%) completed a questionnaire and 104 (75%) had a clinical examination and blood sampling performed....... Eighty-five of 94 (90%) eligible sibling controls completed a similar questionnaire. Siblings had no clinical examination or blood sampling performed. RESULTS: At a median of 11 years (range 4-25) after diagnosis, renal, gastrointestinal, and hepatic disorders were rare both in survivors of childhood AML...

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

    Energy Technology Data Exchange (ETDEWEB)

    Litt, P

    2000-07-01

    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.

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

    International Nuclear Information System (INIS)

    Litt, P.

    2000-01-01

    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

  12. Lille Apathy Rating Scale and MDS-UPDRS for Screening Apathy in Parkinson's Disease.

    Science.gov (United States)

    Weintraut, Rita; Karádi, Kázmér; Lucza, Tivadar; Kovács, Márton; Makkos, Attila; Janszky, József; Kovács, Norbert

    2016-01-01

    Apathy is a syndrome characterized primarily by lack of motivation which may be associated with cognitive, affective and behavioral changes. Although the Lille Apathy Scale (LARS) has been extensively utilized in PD for detecting apathy and testing the effectiveness of specific therapeutic interventions, the highly variable cut-off values (between -11 and -22 points) ensures the applicability of the LARS degree of difficulty as a superb screening tool. The aim of this study is to determine more reliable threshold values based on the neuropsychiatric status of patients. Depression was assessed utilizing the Montgomery-Asberg Depression Rating Scale and neurocognitive status by Addenbrooke's Cognitive Examination. The presence of apathy was assessed by the proposed diagnostic criteria of Drijgers et al, and graded by both LARS and the 'Apathy' item of MDS-UPDRS. Based on multivariate regression analysis, we revealed the neurocognitive status, severity of depression, and also gender while applying dosage of dopamine agonists to determine the degree of patient apathy. Based on whether or not depression and neurocognitive disorders were indeed present, we established four different threshold values for the LARS: patients with normal cognition and without depression: -22.5; patients with normal cognition and with depression: -18.5; patients with NCD and without depression: -19.5; patients with NCD and with depression: -14.5. The LARS and the 'Apathy' item of MDS-UPDRS were confirmed to be potentially operational, beneficial and easy-to-assess instruments for detecting apathy syndrome in PD. However, there is no universal threshold value for the LARS suitable in all types of Parkinson's patients.

  13. Ein Integraler Gestalt-Ansatz fuer Therapie und Beratung

    Directory of Open Access Journals (Sweden)

    Reinhard Fuhr

    2005-06-01

    Full Text Available In diesem Text stellen wir unseren Ansatz für Psychotherapie und Beratung auf dem Hintergrund des integralen Paradigmas dar. Wir erläutern zunächst kurz vier Anforderungen an ein integrales Konzept in diesem professionellen Bereich: Umgang mit Komplexität und Vielperspektivität, Berücksichtigung gerichteter, vieldimensionaler Entwicklung, Orientierungs- und Sinngebungsfunktion, Realisierung relationaler Qualitäten in der Arbeit. Nach einer Begriffsbestimmung von „Therapie“, „Beratung“ und „Bildung“ charakterisieren wir das seit vielen Jahren von uns entwickelte Konzept für den Integralen Gestalt-Ansatz unter den Fragen nach (1 den Intentionen und Aufgaben von Therapie und Beratung, (2 der Gestaltung der Kommunikation und Beziehung, (3 der Art der Problemdefinition und dem Umgang mit Diagnostik sowie (4 den Strategien und Methoden - alle unter Rückkopplung an die zuvor erläuterten Anforderungen an ein integrales Konzept.

  14. Systemlieferant und OEM Hersteller für die Medizintechnik und Pharmabranche

    Science.gov (United States)

    Jakob, Thomas; Reichenberger, Robert

    Unter einem Original Equipment Manufacturer (OEM) versteht man einen Hersteller fertiger Komponenten oder Produkte, der diese in seinen eigenen Produktionsfabriken produziert, sie aber anschließend nicht selbst in den Handel bringt. Die Anforderungen an einen OEM für die Medizintechnik- und Pharmabranche sind weitaus komplexer und umfangreicher als in anderen Branchen. Diese zusätzlichen Anforderungen haben schließlich auch ihre Berechtigung, da es letztendlich immer um die Gesundheit und das Leben von Menschen geht. Ein OEM muss neben der heute immer stärker geforderten Flexibilität, Schnelligkeit und Wettbewerbsfähigkeit sämtliche für die Medizintechnik- und Pharmabranche erforderlichen Qualitäts- und Prozesssicherheitskriterien erfüllen. Entsprechende Nachweise sind durch regelmäßige Kunden- und Überwachungsaudits zu erbringen. Das Arbeitsumfeld eines OEM für die Medizintechnik- und Pharmabranche bezieht sich somit nicht nur auf die Herstellung der Produkte für seine Kunden, sondern auch auf die Einhaltung sämtlicher Normen, Sicherheitskriterien, regulatorischen Voraussetzungen und Gesetze die zur Herstellung der Produkte notwendig sind.

  15. PHP und MySQL der Web-Baukasten fur Einsteiger und Individualisten

    CERN Document Server

    Damaschke, Giesbert

    2015-01-01

    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,

  16. Kommunikation und Lernen in partizipativen kulturellen und medialen Räumen

    Directory of Open Access Journals (Sweden)

    Elke Zobl

    2012-12-01

    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.

  17. Symmetriebrechung und Emergenz in der Kosmologie.

    Science.gov (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.

  18. Unternehmenssoftware-Ausbildung: Aktueller Stand und Trends

    OpenAIRE

    Mohr, Matthias; Schubert, Uta; Wittges, Holger; Krcmar, Helmut; Schrader, Heino

    2014-01-01

    Im Herbst 2007 wurde nach 2005, 2006 sowie Fr?hjahr 2007 die vierte Bildungsbe-darfsanalyse unter den ca. 2.200 registrierten Dozenten durchgef?hrt, die im Rah-men des SAP University Alliances (UA) Programms an deutschen Hochschulen und anderen Bildungsinstitutionen Lehre zu SAP-bezogenen Themen durchf?hren. Ziel war es, einen ?berblick ?ber SAP-Themen in Forschung und Lehre zu erhalten. 249 Dozenten (ca. 11 Die Kernaussagen der Studie sind die folgenden: 1. Die ECC-Kernkomponenten und BW sin...

  19. Unternehmenssoftware-Ausbildung: Aktueller Stand und Trends

    OpenAIRE

    Schubert, Uta; Wittges, Holger; Krcmar, Helmut; Schrader, Heino

    2014-01-01

    Im Fr?hjahr 2008 wurde die 5. Bildungsbedarfsanalyse (BBA) unter ca. 2.450 registrierten Dozenten (UCC-Dozenten-Community) durchgef?hrt, die im Rahmen des SAP University Alliances (UA) Programms an deutschen Hochschulen und anderen Bildungs?institutionen Lehre zu SAP-bezogenen Themen durchf?hren. Ziel war es, einen ?berblick ?ber SAP-Themen in Forschung und Lehre zu erhalten. 54 Dozenten (2,2 Die Kernaussagen der Studie sind: 1. Die ECC-Kernkomponenten und BW sind die in der Lehre am h?ufigst...

  20. Religionsunterricht vor theologischen und gesellschaftlichen Herausforderungen

    Directory of Open Access Journals (Sweden)

    Lothar Kuld

    2013-10-01

    Full Text Available Die Wiederkehr der Religion und neuer Atheismus, religiöser Traditionsbruch und religiöse Optionsvielfalt beschreiben die widersprüchlichen theologischen und gesellschaftlichen Herausforderungen, vor denen der Religionsunterricht heute steht. Als Teil des Bildungssystems hat er die Tradierung von Religion übernommen. Religiöse Bildung ist die Voraussetzung dafür, dass Menschen als Individuen überhaupt eine vernünftige religiöse Identität entwickeln können.

  1. Editorial: Theoriebildung in Mediendidaktik und Wissensmanagement

    Directory of Open Access Journals (Sweden)

    Michael Kerres

    2002-10-01

    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

  2. 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.

    1998-01-01

    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

  3. Treatment, risk factors, and outcome of adults with relapsed AML after reduced intensity conditioning for allogeneic stem cell transplantation

    NARCIS (Netherlands)

    C. Schmid (Christoph); M. Labopin (Myriam); A. Nagler (Arnon); D. Niederwieser (Dietger); L. Castagna (Luca); R. Tabrizi (Reza); M. Stadler (Michael); J. Kuball (Jürgen); J.J. Cornelissen (Jan); J. Vorlicek (Jiri); G. Socié (Gerard); M. Falda (M.); L. Vindelov (Lars); P. Ljungman (Per); G. Jackson (Graham); N. Kröger (Nicolaus); A. Rank (Andreas); E. Polge (Emmanuelle); V. Rocha (Vanderson); M. Mohty (Mohamad)

    2012-01-01

    textabstractBecause information on management and outcome of AML relapse after allogeneic hematopoietic stem cell transplantation (HSCT) with reduced intensity conditioning (RIC) is scarce, a retrospective registry study was performed by the Acute LeukemiaWorking Party of EBMT. Among 2815 RIC

  4. Treatment, risk factors, and outcome of adults with relapsed AML after reduced intensity conditioning for allogeneic stem cell transplantation

    DEFF Research Database (Denmark)

    Schmid, Christoph; Labopin, Myriam; Nagler, Arnon

    2012-01-01

    Since information on management and outcome of adults with AML relapsing after allogeneic hematopoietic stem cell transplantation with reduced intensity conditioning (RIC HSCT) is scarce, a retrospective registry study was performed by the Acute Leukemia Working Party of EBMT. Among 2815 RIC tran...

  5. RT-PCR and real-time PCR analysis of E2A-PBX1, TEL-AML1 ...

    Indian Academy of Sciences (India)

    Home; Journals; Journal of Genetics; Volume 90; Issue 2. RT-PCR and real-time PCR analysis of E2A-PBX1, TEL-AML1, mBCR-ABL and MLL-AF4 fusion gene transcripts in de novo B-lineage acute lymphoblastic leukaemia patients in south India. Natarajan Sudhakar Kamalalayam Raghavan Rajalekshmy Thangarajan ...

  6. 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.

    2012-01-01

    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

  7. Protracted and variable latency of acute lymphoblastic leukemia after TEL-AML1 gene fusion in utero

    NARCIS (Netherlands)

    Wiemels, JL; Ford, AM; Van Wering, ER; Postma, A; Greaves, M

    1999-01-01

    We report a pair of identical twins with concordant acute lymphoblastic leukemia (ALL). Unusually, their diagnoses were spaced 9 years apart at ages 5 and 14, Leukemic cells in both twins had a TEL-AML1 rearrangement, which was characterized at the DNA level by an adaptation of a long distance

  8. The potential association of the transcription levels of the ABO gene with the disease phases in AML patients.

    Science.gov (United States)

    Zhang, Wenjing; Liu, Jinling; Zhang, Wei; Zhuang, Yunlong

    2017-10-01

    Patients with AML may show ABO blood typing discrepancy, and the expression levels of the ABO antigens may show some alterations with the disease progression. To better understand this phenomenon, the blood samples of 25 AML patients and 25 healthy blood donors were examined. The serological ABO blood types of the patients were determined in different AML stages, and gene sequencing was performed to identify the precise ABO genotypes. Reverse transcription-polymerase chain reaction (RT-PCR) was carried out to detect the transcription levels of the antigens. The genotyping result showed that there were 4 patients with genotype A 1 O, 5 patients with B 1 O, and 16 patients with A 1 B 1 . RT-PCR results indicated that the transcription levels of the ABO gene in 76% (19/25) of the patients were significantly lower compared with those in controls (p ABO gene from those of controls. The data indicated that the transcription levels of the ABO gene changed with the disease progression, suggesting its potential role in the progression of AML disease. Copyright © 2017 Elsevier Ltd. All rights reserved.

  9. Individualized vaccination of AML patients in remission is associated with induction of antileukemia immunity and prolonged remissions.

    Science.gov (United States)

    Rosenblatt, Jacalyn; Stone, Richard M; Uhl, Lynne; Neuberg, Donna; Joyce, Robin; Levine, James D; Arnason, Jon; McMasters, Malgorzata; Luptakova, Katarina; Jain, Salvia; Zwicker, Jeffrey I; Hamdan, Ayad; Boussiotis, Vassiliki; Steensma, David P; DeAngelo, Daniel J; Galinsky, Ilene; Dutt, Poorvi Somaiya; Logan, Emma; Bryant, Mary Paty; Stroopinsky, Dina; Werner, Lillian; Palmer, Kristen; Coll, Max; Washington, Abigail; Cole, Leandra; Kufe, Donald; Avigan, David

    2016-12-07

    We developed a personalized cancer vaccine in which patient-derived acute myeloid leukemia (AML) cells are fused with autologous dendritic cells, generating a hybridoma that potently stimulates broad antitumor responses. We report results obtained from the first 17 AML patients, who achieved remission after chemotherapy and were then serially vaccinated to target minimal residual disease and prevent relapse. Vaccination was well tolerated and induced inflammatory responses at the site of administration, characterized by the dense infiltration of T cells. Vaccination was also associated with a marked rise in circulating T cells recognizing whole AML cells and leukemia-specific antigens that persisted for more than 6 months. Twelve of 17 vaccinated patients (71%; 90% confidence interval, 52 to 89%) remain alive without recurrence at a median follow-up of 57 months. The results demonstrate that personalized vaccination of AML patients in remission induces the expansion of leukemia-specific T cells and may be protective against disease relapse. Copyright © 2016, American Association for the Advancement of Science.

  10. Co-inhibition of NF-κB and JNK is synergistic in TNF-expressing human AML

    Science.gov (United States)

    Volk, Andrew; Li, Jing; Xin, Junping; You, Dewen; Zhang, Jun; Liu, Xinli; Xiao, Yechen; Breslin, Peter; Li, Zejuan; Wei, Wei; Schmidt, Rachel; Li, Xingyu; Zhang, Zhou; Kuo, Paul C.; Nand, Sucha; Zhang, Jianke; Chen, Jianjun

    2014-01-01

    Leukemic stem cells (LSCs) isolated from acute myeloid leukemia (AML) patients are more sensitive to nuclear factor κB (NF-κB) inhibition-induced cell death when compared with hematopoietic stem and progenitor cells (HSPCs) in in vitro culture. However, inadequate anti-leukemic activity of NF-κB inhibition in vivo suggests the presence of additional survival/proliferative signals that can compensate for NF-κB inhibition. AML subtypes M3, M4, and M5 cells produce endogenous tumor necrosis factor α (TNF). Although stimulating HSPC with TNF promotes necroptosis and apoptosis, similar treatment with AML cells (leukemic cells, LCs) results in an increase in survival and proliferation. We determined that TNF stimulation drives the JNK–AP1 pathway in a manner parallel to NF-κB, leading to the up-regulation of anti-apoptotic genes in LC. We found that we can significantly sensitize LC to NF-κB inhibitor treatment by blocking the TNF–JNK–AP1 signaling pathway. Our data suggest that co-inhibition of both TNF–JNK–AP1 and NF-κB signals may provide a more comprehensive treatment paradigm for AML patients with TNF-expressing LC. PMID:24842373

  11. A cryptic translocation leading to NUP98-PHF23 fusion in AML.

    Science.gov (United States)

    Ning, Yi

    2016-12-01

    Chromosome translocations leading to gene fusions have emerged as important oncogenic drivers of various types of malignancies. Detection and characterization of these fusion genes not only help diagnosis and management of specific malignancies, but also contribute to our understanding of the genetic basis and pathogenesis of these diseases. NUP98 gene encodes a 98 kDa nucleoporin, which is a component of the nuclear pore complex that mediates transport of mRNA and proteins between the nucleus and the cytoplasm. Due to its participation in translocations leading to the formation of fusion with at least 29 different partner genes, NUP98 is considered one of the most promiscuous fusion genes in hematologic malignancies. We discuss our identification and characterization of a NUP98-PHF23 fusion from a cryptic translocation in patients with acute myeloid leukemia (AML). Copyright © 2016 Elsevier Ltd. All rights reserved.

  12. Donor-Derived Smoldering Multiple Myeloma following a Hematopoietic Cell Transplantation for AML

    Directory of Open Access Journals (Sweden)

    Bita Fakhri

    2017-01-01

    Full Text Available Posttransplant Lymphoproliferative Disorder (PTLD is one of the most common malignancies complicating solid organ transplantation. In contrast, PTLD accounts for a minority of secondary cancers following allogeneic hematopoietic cell transplantation (HCT. Here we report on a 61-year-old woman who received an ABO-mismatched, HLA-matched unrelated donor hematopoietic cell transplantation from a presumably healthy donor for a diagnosis of acute myeloid leukemia (AML. Eighteen months following her transplant, she developed a monoclonal gammopathy. Bone marrow studies revealed 10% plasma cells, but the patient lacked clinical defining features of multiple myeloma (MM; thus a diagnosis of smoldering multiple myeloma (SMM was established. Cytogenetic and molecular studies of the bone marrow confirmed the plasma cells were donor-derived. The donor lacks a diagnosis of monoclonal gammopathy of undetermined significance, SMM, or MM.

  13. Donor-Derived Smoldering Multiple Myeloma following a Hematopoietic Cell Transplantation for AML.

    Science.gov (United States)

    Fakhri, Bita; Fiala, Mark; Slade, Michael; Westervelt, Peter; Ghobadi, Armin

    2017-01-01

    Posttransplant Lymphoproliferative Disorder (PTLD) is one of the most common malignancies complicating solid organ transplantation. In contrast, PTLD accounts for a minority of secondary cancers following allogeneic hematopoietic cell transplantation (HCT). Here we report on a 61-year-old woman who received an ABO-mismatched, HLA-matched unrelated donor hematopoietic cell transplantation from a presumably healthy donor for a diagnosis of acute myeloid leukemia (AML). Eighteen months following her transplant, she developed a monoclonal gammopathy. Bone marrow studies revealed 10% plasma cells, but the patient lacked clinical defining features of multiple myeloma (MM); thus a diagnosis of smoldering multiple myeloma (SMM) was established. Cytogenetic and molecular studies of the bone marrow confirmed the plasma cells were donor-derived. The donor lacks a diagnosis of monoclonal gammopathy of undetermined significance, SMM, or MM.

  14. 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

    2013-01-01

    caused by other microorganisms. VGS were involved in 45% of all episodes categorized as sepsis (n = 51) and in 67% of life-threatening bloodstream infections (n = 9). Penicillin resistance was found in 40% of the VGS strains. No significant difference was observed in the proportion of VGS isolated......BACKGROUND: High-dose cytarabine has been associated with a high frequency of viridans group streptococcal (VGS) bacteraemia. VGS bacteraemia causes considerable morbidity and mortality. The Nordic Society of Paediatric Haematology and Oncology (NOPHO)-AML protocols use higher cumulated doses...... following courses with low-dose cytarabine versus courses with high-dose cytarabine. CONCLUSIONS: VGS were the most commonly isolated pathogens causing the most severe infections and the majority of life-threatening infections. A substantial proportion of the strains were resistant to penicillin. The high...

  15. MRD in AML: it is time to change the definition of remission.

    Science.gov (United States)

    Ossenkoppele, Gert J; Schuurhuis, Gerrit Jan

    2014-01-01

    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.

  16. Rückenschmerzen und Modic

    DEFF Research Database (Denmark)

    Manniche, Claus; Krauff, Hasso; Mikkelsen, Connie

    . Anfangs eine eine schwere Erkennnis für viele meiner damaligen Kollegen, aber seit 1988 hat die Trainingsmethode ihren weltweiten Siegeszug angetreten, und Rückentraining - in verschiedenen Schattierungen – ist heute eine selbstverständliche Behandlung für Patienten mit Rückenschmerzen. Seither wurde auf...... dem Gebiet der Wirbelsäulenforschung nicht so viel Neuland gewonnen, aber heute sind wir endlich einen großen Schritt weiter gekommen mit der Entdeckung der neuen Rückendiagnose Modic – Veränderungen. Über die kommenden Jahre werden Tausende Rückenpatienten, denen wir früher nicht helfen, geschweige....... Das Buch gibt einen Abriß davon, was das neue Wissen konkret für Sie als Rückenpatient bedeutet, außerdem finden Sie hier Antwort auf die Frage, wie Modic – Veränderungen entstehen, wie der Zustand sich entwickelt und wie es dazu gekommen ist, daß wir heute eine Behandlung anbieten können, die bei 50...

  17. [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

    2009-01-01

    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 http://www.historiaurbium.org/english/attivita_images_en.html.

  18. Johannes-Dieter Steinert. Deportation und Zwangsarbeit. Polnische und sowjetische Kinder im nationalsozialistischen Deutschland und im besetzten Osteuropa 1939–1945.

    Directory of Open Access Journals (Sweden)

    Mark Edele

    2015-01-01

    Full Text Available Johannes-Dieter Steinert. Deportation und Zwangsarbeit. Polnische und sowjetische Kinder im nationalsozialistischen Deutschland und im besetzten Osteuropa 1939–1945. [Deportation and Forced Labour. Polish and Soviet Children in Nazi Germany and Occupied Eastern Europe 1939-1945] Essen: Klartext Verlag, 2013. 306 pp. Bibliography. Paper.

  19. 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

    2012-01-01

    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

  20. Circumvention of ara-C resistance by aphidicolin in blast cells from patients with AML.

    Science.gov (United States)

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

    2001-03-02

    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.

  1. Hochstift und Domkapitel Augsburg in Tirol

    OpenAIRE

    Wüst, Wolfgang

    1989-01-01

    Hochstift und Domkapitel Augsburg in Tirol : Herrschaftsgeschichte, Verwaltungsorganisation u. wirtschaftl. Bedeutung. - In: Schwaben - Tirol / [Hrsg.: Wolfram Baer ...] - Rosenheim : Rosenheimer Verlagshaus. - Beiträge. - 1989. - S. 103-116

  2. Kosmische Katastrophen und der Ursprung der Religion.

    Science.gov (United States)

    Hoyle, F.

    This book is a German translation, by V. Delavre, from the English original "The origin of the Universe and the origin of religion", published in 1993. Contents: E. Sens: Die unterbrochene Musikstunde. Einleitung zur deutschen Ausgabe. C. Ryskamp: Einführung. R. N. Anshen: Vorwort. F. Hoyle: Kosmische Katastrophen und der Ursprung der Religion - Die Folgen der Respektabilität; Eiszeiten und Kometen; Die allgemeine Situation in den Nacheiszeiten; Kometen und der Ursprung der Religionen; Der Übergang zu Mittelalter und Neuzeit. Diskussionsbeiträge: Ruth Nanda Anshen, Freeman Dyson, Paul Oscar Kristeller, John Archibald Wheeler, James Schwartz, Roger Shinn, Milton Gatch, Philip Solomon, Norman Newell. F. Hoyle: Schlußwort. A. Tollmann: Nachwort zur deutschen Ausgabe.

  3. Riots ‒ Anmerkungen zu Begriff und Konzept

    Directory of Open Access Journals (Sweden)

    Dieter Rucht

    2016-05-01

    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.

  4. Struktur und Dynamik in der Netzwerkanalyse

    NARCIS (Netherlands)

    Trier, M.; Stegbauer, C.; Häußling, R.

    2010-01-01

    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

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

    Science.gov (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

    2018-03-06

    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.

  6. [mRNA expression of notch ligand-delta-like-1 and jagged-1 in mesenchymal stem cells of MDS patients].

    Science.gov (United States)

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

    2014-12-01

    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.

  7. Progression of MDS-UPDRS Scores Over Five Years in De Novo Parkinson Disease from the Parkinson's Progression Markers Initiative Cohort.

    Science.gov (United States)

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

    2018-01-01

    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.

  8. Judenschutz und Eigennutz. Auseinandersetzungen um Juden an der Ostgrenze des Römisch-Deutschen Reiches im 13. und 14. Jahrhundert.

    OpenAIRE

    Bürstenbinder, Jürgen

    2010-01-01

    Judenschutz und Eigennutz. Auseinandersetzungen um die Juden an der Ostgrenze des Römisch-Deutschen Reiches im 13. und 14. Jahrhundert Jürgen Bürstenbinder Die Publikation beschreibt und analysiert Aspekte jüdischen Lebens in den Gebieten von Mecklenburg, Pommern, Brandenburg, Böhmen, Mähren, Schlesien und Polen im 13. und 14. Jahrhundert. Hauptsächlich werden zeitgenössische Quellen wie Staatsschriften, Schutzbriefe, Verträge, Stadtbücher, Steuerlisten, Beschriftungen von Grabsteinen und and...

  9. Die Rangfolge psychischer und sozialer Prädiktoren und Kriterien für die Prognose Herztransplantierter

    OpenAIRE

    Meyendorf, Rudolf; Stuber, Elke; Piesbergen, Christoph; Reichart, Bruno; Kreuzer, E.; Überfuhr, P.; Welz, A.

    1997-01-01

    Bei 44 Herztransplantierten wurden präoperativ und bis zu einem und drei Jahre postoperativ psychiatrisch/psychologische Untersuchungen durchgeführt und psychosoziale Daten erhoben. Die Prädiktoren und Kriterien für eine gute Prognose wurden ihrer Rangfolge nach hierarchisiert. Es ergab sich folgende Prädiktorrangfolge: 1. die eindeutige Motivation und der unauffällige psychopathologische Befund, 2. der gute soziale Rückhalt und die vor der Transplantation zum Ausdruck gebrachte positive Beru...

  10. Psychoanalyse und weibliche Sexualität

    OpenAIRE

    Mitscherlich, Margarete

    2013-01-01

    Die Erforschung der embryologischen Genese der Geschlechtsdifferenzierung und der Physiologie der sexuellen Funktionen beider Geschlechter hat zu Resultaten geführt, die bestimmte sexualtheoretische Thesen falsifizieren, die Freud - fußend auf dem Erkenntnisstand seiner Zeit und geleitet von undurchschauten Ideologien über eine »natürliche" Minderwertigkeit der Frau - entwickelt hatte. Der menschliche Embryo ist primär weiblich organisiert; die Klitoris kann darum nicht als ein ;erkümmerter P...

  11. Climate and transportation; Klima und Verkehr

    Energy Technology Data Exchange (ETDEWEB)

    Fabian, P. [Muenchen Univ. (Germany). Lehrstuhl fuer Bioklimatologie und Immissionsforschung

    1996-06-01

    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)

  12. Polen, Deutschland, die EU und Russland

    OpenAIRE

    Wilkiewicz, Zbigniew

    2009-01-01

    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...

  13. Medien als Lernform und die Trimediale Redaktion

    Directory of Open Access Journals (Sweden)

    Wolf Hilzensauer

    2015-01-01

    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.

  14. Nutzung und Akzeptanz von E-Commerce

    OpenAIRE

    Schenk, Michael; Wolf, Malthe

    2001-01-01

    Marktprognosen bescheinigen, auch nach dem weltweiten Einbruch der Neuen Märkte und der daraufhin einsetzenden Ernüchterung, dem elektronischen Handel eine große Zukunft. Business-Transaktionen verändern sich rapide unter dem Einfluss elektronischer Kommunikationstechnologien. Wenngleich auch erwartet wird, dass sich Business-to-Consumer E-Commerce weltweit als erfolgreicher Vertriebs- und Kommunikationskanal etablieren wird, stößt E-Commerce derzeit noch nicht auf die erhoffte Akzeptanz in b...

  15. Kurz zum Klima: Schiefergas und Fracking

    OpenAIRE

    Ursula Triebswetter; Jana Lippelt

    2012-01-01

    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.

  16. Kolloide in externen elektrischen und magnetischen Feldern

    OpenAIRE

    Zhao, Jinyu

    2011-01-01

    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...

  17. Neue Technologien und Erziehung/Bildung

    Directory of Open Access Journals (Sweden)

    Norbert Meder

    2015-03-01

    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

  18. Analytische Kinder- und Jugendlichenpsychotherapie bei Schulverweigerung

    OpenAIRE

    Oelsner, Wolfgang

    2003-01-01

    Das Phänomen Schulverweigerung wird differentialdiagnostisch unter Schulschwänzen, Schulangst und Schulphobie diskutiert. Analytische Kinder- und Jugendlichenpsychotherapie wird vorrangig bei Schulphobie indiziert gesehen. Es handelt sich um eine Trennungsangst des Kindes, die in dyadischen Beziehungsstrukturen fixiert ist. Um einen Triangulierungsprozess therapeutisch zu forcieren, dürfen die als Verweigerung ausagierten Widerstände sich nicht weiter etablieren. Wenn es nicht zu...

  19. Analytische Kinder- und Jugendlichenpsychotherapie bei Schulverweigerung

    OpenAIRE

    Oelsner, Wolfgang

    2003-01-01

    Das Phänomen Schulverweigerung wird differentialdiagnostisch unter Schulschwänzen, Schulangst und Schulphobie diskutiert. Analytische Kinder- und Jugendlichenpsychotherapie wird vorrangig bei Schulphobie indiziert gesehen. Es handelt sich um eine Trennungsangst des Kindes, die in dyadischen Beziehungsstrukturen fixiert ist. Um einen Triangulierungsprozess therapeutisch zu forcieren, dürfen die als Verweigerung ausagierten Widerstände sich nicht weiter etablieren. Wenn es nicht zur baldigen Au...

  20. Positionsbestimmung des Unternehmens: Interne und externe Analyse

    Science.gov (United States)

    Bergmann, Lars; Crespo, Isabel; Portmann, Stefan

    Die Initiierung und Lenkung von Maßnahmen zur integrierten Modernisierung zielen auf die Verbesserung der Wettbewerbsfähigkeit eines Unternehmens ab. Damit diese Maßnahmen zielgerichtet die Wettbewerbsfähigkeit verbessern können, ist Wissen über die bestehende Wettbewerbsfähigkeit sowie über die bestehenden Fähigkeiten eine zentrale Voraussetzung. Eine zielgerichtete Auswahl problemadäquater Maßnahmen zur Verbesserung der Wettbewerbsfähigkeit bedarf daher im Vorfeld einer Bewertung der aktuellen Situation des Unternehmens im Sinne einer Positionsbestimmung. Erst wenn die internen Stärken und Schwächen sowie die externen Chancen und Risiken identifiziert sind, kann ein ganzheitliches Bild von der Position eines Unternehmens in seiner Umwelt gewonnen werden. Auf Basis der Kenntnisse über die Position des Unternehmens können anschließend zielgerichtet Maßnahmen ausgewählt werden, die einen Beitrag zur Verbesserung der Wettbewerbsfähigkeit des Unternehmens haben. Damit kommt der Positionsbestimmung als initialer Schritt des Prozesses der strategischen Unternehmensplanung eine zentrale Bedeutung im Rahmen der integrierten Modernisierung zu. Erfolgt die Auswahl von Maßnahmen ohne eine vorherige Positionsbestimmung, also lediglich auf Basis drängender Probleme, so besteht die Gefahr einer unbedachten und nur auf das "hier und heute“ bezogenen Schwerpunktbildung ohne Berücksichtigung der mittel- und langfristigen Ziele des Unternehmens.

  1. RANK und RANKL - Vom Knochen zum Mammakarzinom

    Directory of Open Access Journals (Sweden)

    Sigl V

    2012-01-01

    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.

  2. Gesundheitsbewußtsein, berufliche Belastung und Bewältigungsverhalten von ärztlichen und psychologischen Psychotherapeuten : unter Berücksichtigung von Kinderpsychiatern und Kinderpsychotherapeuten

    OpenAIRE

    Müller, Ute Wilma

    2007-01-01

    Psychotherapeuten sollten, um eine qualitativ gute Therapie machen zu können, so gesund wie möglich sein, geistig, seelisch und körperlich. Diese Arbeit untersucht, ob sich Psychotherapeuten entsprechend ihres Fachwissens selber gesund verhalten und für sich sorgen und wie sie im Hinblick auf ihre berufliche Belastung ihre Ausbildung und Berufszufriedenheit einschätzen. Bei der Erfassung des Gesundheits- und Bewältigungsverhaltens lag neben allgemein bekannten Gesundheitsmaßnahmen ein Aug...

  3. Aus Wirtschaft und Betrieb. Biomasse: Gewinnung und Verarbeitung mit Profilschal-maschinen

    Science.gov (United States)

    P. Koch

    1977-01-01

    1963 wurden in den Südstaaten der USA nur 30% der oberund unterirdischen Biomasse der geernteten sog. Southern pines für Schnittholz und Zellstoff verwertet bzw. als getrockneies, gehobletes und abgelängtes Schnittholz oder als Kraftpapier verkauft. Keine der zusammen mit den Kiefern vorkommenden Laubholzarten wurde bisher in nennenswertem Umfan verwertet. Auch heute...

  4. Alexander Kratochvil. Aufbruch und Rückkehr: Ukrainische und tschechische Prosa im Zeichen der Postmoderne.

    Directory of Open Access Journals (Sweden)

    Marko Pavlyshyn

    2015-01-01

    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.

  5. Application of Multidimensional Scaling (MDS) to the analysis of media discourse. The case of the media coverage of ‘escraches’

    OpenAIRE

    Albizu Landa, Xabier

    2014-01-01

    En el presente artículo se discuten las posibilidades que ofrece la técnica de análisis multivariante conocida como Escalamiento Multidimensional (MDS) para el análisis del discurso periodístico y la determinación de los frames presentes en este. En una primera parte se repasan las tradiciones de los análisis de framing y de la aplicación del MDS. En una segunda parte se presenta un caso práctico en el que el MDS es utilizado para la determinación de los frames presentes en la cobertura perio...

  6. 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-

    2011-01-01

    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

  7. [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-

    2010-01-01

    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)

  8. Neue Medien in der Lehrerausbildung. Zu angemessenen (und unangemessenen Zielen und Inhalten des Lehramtsstudiums

    Directory of Open Access Journals (Sweden)

    Sigrid Blömeke

    2003-01-01

    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.

  9. Die Werte der Wertvermittler - Berufliches Rollenselbstverständnis und Weltanschauung von Journalistinnen und Journalisten

    Directory of Open Access Journals (Sweden)

    Andy Kaltenbrunner

    2010-09-01

    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.

  10. Hinkelbeinchen und "little chicken's leg": deutsche und amerikanische Idiome als kommunikative Textsorten-Problematik

    Directory of Open Access Journals (Sweden)

    Martin Wierschin

    1998-12-01

    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.

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

    Science.gov (United States)

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

    2017-09-15

    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 previous peptide microarray. PLC-γ1 is known to play a role in cancer progression, however, the impact of PLC-γ1 in AML is currently unknown. Therefore, we aimed to study the functional role of PLC-γ1 by investigating the cellular growth, survival and its underlying mechanism in t(8;21) AML. In this study, PLC-γ1 expression was significantly higher in t(8;21) AML compared to other karyotypes. The PLC-γ1 protein expression was suppressed in AML1-ETO knock down cells indicating that it might induce kasumi-1 cell death. ShRNA-mediated PLC-γ1 knockdown in kasumi-1 cells significantly blocked cell growth, induced apoptosis and cell cycle arrest which was explained by the increased activation of apoptotic related and cell cycle regulatory protein expressions. Gene expression array analysis showed the up-regulation of apoptotic and DNA damage response genes together with the downregulation of cell growth, proliferation and differentiation genes in the PLC-γ1 suppressed kasumi-1 cells, consistent with the observed phenotypic effects. Importantly, PLC-γ1 suppressed kasumi-1 cells showed higher chemosensitivity to the chemotherapeutic drug treatments and lower cell proliferation upon hypoxic stress. Taken together, these in vitro finding strongly support an important role for PLC-γ1 in the survival of t(8;21) AML mimicking kasumi-1 cells and identify PLC-γ1 as a potential therapeutic target for t(8;21) AML treatment.

  12. The rarity of ALDH(+) cells is the key to separation of normal versus leukemia stem cells by ALDH activity in AML patients.

    Science.gov (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

    2015-08-01

    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.

  13. Louis Perridon und die Augsburger Sozioökonomie

    OpenAIRE

    Reimann, Horst

    1984-01-01

    Louis Perridon und die Augsburger Sozioökonomie. - In: Hochschulpolitik und Wissenschaftskonzeptionen bei der Gründung der Universität Augsburg. - Augsburg, 1984. - S. 15-27. - (Augsburger Universitätsreden ; 3)

  14. Quantenmechanik im Kalten Krieg David Bohm und Richard Feynman

    CERN Document Server

    Forstner, Christian

    2007-01-01

    Mitte des 20. Jahrhunderts entwickelten David Bohm und Richard Feynman zwei grundlegend verschiedene Ansätze der moderne Quantenmechanik: Bohm eine realistische Deutung mit Hilfe verborgener Parameter und Feynman den Pfadintegralformalismus. Dies ist umso bemerkenswerter, weil beide Physiker von ähnlichen Voraussetzungen ausgingen und aus ähnlichen Zusammenhängen stammten. Durch ihren vergleichenden Ansatz bietet diese Studie mehr als einen Beitrag zur Geschichte der Quantentheorie. Mit der Frage nach den sozialen und kulturellen Bedingungen der Theoriebildung ist sie darüberhinaus von wissenschaftssoziologischem und wissenschaftstheoretischem Interesse. Die anfangs ähnliche und später unterschiedliche Einbindung der beiden Wissenschaftler in die Scientific Community erlaubt es überdies zu untersuchen, welchen Anpassungsdruck die jeweilige Gruppe auf den individuellen Wissenschaftler und die Kernbestandteile seiner Forschungen ausübt und welche neuen Freiheitsgrade für die Theoriebildung entstehen, ...

  15. 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

    2013-06-01

    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.

  16. Genetics of therapy-related myelodysplasia and acute myeloid leukemia

    DEFF Research Database (Denmark)

    Pedersen-Bjergaard, J.; Andersen, Mette Klarskov; Andersen, M.T.

    2008-01-01

    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...

  17. Differentielle Regulation der Chemokinsynthese in Alveolarepithelzellen durch Stickstoff- und Sauerstoffradikale

    OpenAIRE

    Bayer, Friederike Christiane

    2003-01-01

    Alveolarepithelzellen beteiligen sich durch Sekretion von Chemokinen und Expression von Adhäsionsmolekülen aktiv am Prozess der Leukozytenrekrutierung in den Alveolarraum. In der vorliegenden Arbeit wurde der Einfluss der Radikale Stickstoffmonoxid (NO), Superoxid (O2-) und ihrem Reaktionsprodukt Peroxynitrit (ONOO-) auf die spontane sowie auf die durch die proinflammatorischen Zytokine IL-1b und TNFa induzierte Synthese der Chemokine IL-8/CXCL8 und MCP-1/CCL2 in Alveolarepithelzellen untersu...

  18. Quasistatische und transiente Oberflächenpotentialverteilungen organischer Feldeffekttransistoren

    OpenAIRE

    Siol, Christopher

    2012-01-01

    In dieser Arbeit wurden organische Feldeffekttransistoren (OFETs) durch orts- und zeitaufgelöste Oberflächenpotentialmessungen untersucht. Hierbei standen langsame Transportphänomene sowie Auf- und Entladeprozesse im Transistorkanal im Vordergrund. Insbesondere wurde das Laden und Entladen von Fallenzuständen analysiert und mit Instabilitäten des Drainstroms korreliert. Im experimentellen Teil wurde ein für in-situ Messungen an OFETs optimiertes System zur Kelvinsondenkraftmikroskopie (K...

  19. Raman-Mikrospektroskopie zur Analyse von organischen Bodensubstanzen und Mikroplastik

    OpenAIRE

    Wiesheu, Alexandra Christina

    2017-01-01

    Im Rahmen der Arbeit wurde die Raman-Mikrospektroskopie für die Analyse unterschiedlicher Umweltproben angewandt und optimiert. Hierbei wurde die Stabilisotopen-Raman-Mikrospektroskopie weiterentwickelt und erstmals für organische Bodensubstanzen verwendet, um eine Analyse mit hoher räumlicher Auflösung zu erhalten. Des Weiteren wurde Mikroplastik aus unterschiedlichen Matrices wie Sedimenten, Organismen und Getränken abgetrennt und identifiziert. This work deals with the application and ...

  20. Beginn und Dosisanpassung einer intensivierten konventionellen Insulintherapie (ICT beim Erwachsenen

    Directory of Open Access Journals (Sweden)

    Lohr R

    2012-01-01

    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.