27 research outputs found

    Citation Analyses in Information Systems

    Get PDF
    Few scientists that specialize in information systems would recognize the name one of the field’s most cited authors, Ike Antkare. It is not that Antkare is from an obscure discipline. This aberration is the result of a vulnerability of citation analyses. A vulnerability proven with a computer program. Today, funding, promotion and tenure extension depend on the results of these analyses. This paper explores the nature of citation analyses in the information systems (IS) field and classifies them based on an adapted framework of Zupic and Cater (2015). The results illustrate two types of citation analyses. The first type contains ranking studies using measures of the h-family index calculated on citation networks. The second type involves co-citation analysis applying cluster or factor analysis to determine the intellectual structure, trajectory or maturity

    "(Er)kenne Dich selbst". Eine Initiative zur inklusionsorientierten Professionalisierung von (sonder-)pÀdagogischen LehrkrÀften im Förderschwerpunkt Emotionale und Soziale Entwicklung

    Get PDF
    Bettina Amrhein, Benjamin Badstieber, Mareike MĂŒller-Cleve, Cathrin Reisenauer und Malte Thiede stellen zwei Forschungsprojekte vor, in welchen nicht das störende Verhalten von SchĂŒler*innen, sondern die Lehrkraft und ihr VerhĂ€ltnis zu diesem Verhalten in den Mittelpunkt des Interesses gerĂŒckt werden. (DIPF/Orig.

    In Vivo Expansion of Co-Transplanted T Cells Impacts on Tumor Re-Initiating Activity of Human Acute Myeloid Leukemia in NSG Mice

    Get PDF
    Human cells from acute myeloid leukemia (AML) patients are frequently transplanted into immune-compromised mouse strains to provide an in vivo environment for studies on the biology of the disease. Since frequencies of leukemia re-initiating cells are low and a unique cell surface phenotype that includes all tumor re-initiating activity remains unknown, the underlying mechanisms leading to limitations in the xenotransplantation assay need to be understood and overcome to obtain robust engraftment of AML-containing samples. We report here that in the NSG xenotransplantation assay, the large majority of mononucleated cells from patients with AML fail to establish a reproducible myeloid engraftment despite high donor chimerism. Instead, donor-derived cells mainly consist of polyclonal disease-unrelated expanded co-transplanted human T lymphocytes that induce xenogeneic graft versus host disease and mask the engraftment of human AML in mice. Engraftment of mainly myeloid cell types can be enforced by the prevention of T cell expansion through the depletion of lymphocytes from the graft prior transplantation

    Graft-versus-Host disease Prophylaxis with Everolimus and Tacrolimus Is Associated with a High Incidence of Sinusoidal Obstruction Syndrome and Microangiopathy: Results of the EVTAC Trial

    Get PDF
    AbstractA calcineurin inhibitor combined with methotrexate is the standard prophylaxis for graft-versus-host disease (GVHD) after allogeneic hematopoietic stem cell transplantation (HSCT). Everolimus, a derivative of sirolimus, seems to mediate antileukemia effects. We report on a combination of everolimus and tacrolimus in 24 patients (median age, 62 years) with either myelodysplastic syndrome (MDS; n = 17) or acute myeloid leukemia (AML; n = 7) undergoing intensive conditioning followed by HSCT from related (n = 4) or unrelated (n = 20) donors. All patients engrafted, and only 1 patient experienced grade IV mucositis. Nine patients (37%) developed acute grade II-IV GVHD, and 11 of 17 evaluable patients (64%) developed chronic extensive GVHD. Transplantation-associated microangiopathy (TMA) occurred in 7 patients (29%), with 2 cases of acute renal failure. The study was terminated prematurely because an additional 6 patients (25%) developed sinusoidal obstruction syndrome (SOS), which was fatal in 2 cases. With a median follow-up of 26 months, the 2-year overall survival rate was 47%. Although this new combination appears to be effective as a prophylactic regimen for acute GVHD, the incidence of TMA and SOS is considerably higher than seen with other regimens

    Defining the “Positive Impact” of socio-technical systems for absolute sustainability: a literature review based on the identification of system design principles and management functions

    Get PDF
    Socio-technical systems represent complex interactions of humans with ecological, social and economic systems. A system’s design and its operations determine whether its impact is “negative”, “neutral/zero” or “positive” over the system life cycle with regard to its contribution to sustainable development. But coping with exceeded planetary boundaries and social challenges requires more than “net-zero” approaches to achieve biosphere resilience and healthy societies. While negative and zero impacts are widely studied, the term “positive impact” has just recently gained importance to describe the outcome of design, planning, operational, organizational or engineering processes. Various case studies, reviews and conceptual proposals exist—mostly applied in a specific context—but a clear definition is not yet detectable. Based on a review of existing literature, this paper: (i) analyzes current perceptions of negative, zero and positive impacts of socio-technical systems on absolute sustainability, (ii) summarizes the current state of knowledge on positive impact concepts for sustainable development, (iii) identifies relevant socio-technical system design principles for positive impacts on biosphere, society and economy, (iv) derives management functions and organizational prerequisites within socio-technical systems to enable positive impacts, (v) proposes a guiding framework and a definition for “positive impact of socio-technical systems for absolute sustainability”, and (vi) discusses briefly potential applications and further research demand. This review intends to synthesize existing knowledge from an industrial and engineering design perspective, and delivers an overview on the subject from a global sustainability level to the operational level. The derived insights provide a basis for method development, system design processes and new business models

    Combining Life Cycle Assessment and Manufacturing System Simulation: Evaluating Dynamic Impacts from Renewable Energy Supply on Product-Specific Environmental Footprints

    Get PDF
    The eco-efficiency of actual production processes is still one dominating research area in engineering. However, neglecting the environmental impacts of production equipment, technical building services and energy supply might lead to sub-optimization or burden-shifting and thus reduced effectiveness. As an established method used in sustainability management, Life Cycle Assessment aims at calculating the environmental impacts from all life cycle stages of a product or system. In order to cope with shortcomings of the static character of life cycle models and data gaps this approach combines Life Cycle Assessment with manufacturing system simulation. Therefore, the two life cycles of product and production system are merged to assess environmental sustainability on product level. Manufacturing simulation covers the production system and Life Cycle Assessment is needed to relate the results to the final product. This combined approach highlights the influences from dynamic effects in manufacturing systems on resulting life cycle impact from both product and production system. Furthermore, the importance of considering indirect peripheral equipment and its effects on the manufacturing system operation in terms of output and energy demands is underlined. The environmental flows are converted into impacts for the five recommended environmental impact categories. Thus, it can be demonstrate that Life Cycle Assessment can enhance the process simulation and help identify hot-spots along the life cycle. The combined methodology is applied for analysing a case study in fourteen scenarios for the integration of volatile energy sources into energy flexible manufacturing control

    Clonal hematopoiesis and its emerging effects on cellular therapies

    No full text
    The accumulation of somatic mutations in hematopoietic stem cells during aging, leading to clonal expansion, is linked to a higher risk of cardiovascular mortality and hematologic malignancies. Clinically, clonal hematopoiesis is associated with a pro-inflammatory phenotype of hematopoietic cells and their progeny, inflammatory conditions and a poor outcome for patients with hematologic neoplasms and solid tumors. Here, we review the relevance and complications of clonal hematopoiesis for the treatment of hematologic malignancies with cell therapeutic approaches. In autologous and allogeneic hematopoietic stem cell transplantation native hematopoietic and immune effector cells of clonal origin are transferred, which may affect outcome of the procedure. In chimeric antigen receptor modified T-cell therapy, the effectiveness may be altered by preexisting somatic mutations in genetically modified effector cells or by unmodified bystander cells harboring clonal hematopoiesis. Registry studies and carefully designed prospective trials will be required to assess the relative roles of donor- and recipient-derived individual clonal events for autologous and allogeneic cell therapies and to incorporate novel insights into therapeutic strategies

    Human CD3<sup>+</sup> cells in NSG recipient mice are polyclonal activated T lymphocytes.

    No full text
    <p>(A) Human CD3<sup>+</sup> cells are morphologically diverse. Sorted human CD45<sup>+</sup>CD3<sup>+</sup> cells (sort purity: 98.6%) isolated from the bone marrow of a NSG recipient mouse that had received 5×10<sup>6</sup>–10<sup>7</sup> freshly isolated MNCs from AML #10 three weeks before were cytospun and stained according to May-GrĂŒnwald Giemsa. (Graft phenotype in the recipient: bone marrow: 35% hCD45<sup>+</sup>; composition of human leukocytes: CD3<sup>+</sup> = 93%, CD19<sup>+</sup> = 0.8%, CD33<sup>+</sup> = 0.8%; surface antigens on CD3<sup>+</sup> cells: CD4<sup>+</sup> = 80%, CD8<sup>+</sup> = 14%, CD4<sup>+</sup>/CD8<sup>+</sup> = 3%, TCRα/ÎČ<sup>+</sup> = 99%, TCRÎł/ÎŽ<sup>+</sup> = 0.02%). Photograph is representative for 6 different AML samples. Scale bar indicates a section of 10 micrometers. (B) Human CD3<sup>+</sup> cells are identified as T lymphocytes by the surface expression of the T cell receptors (TCRs) and co-receptors. Graph shows a summary of the expression of TCRα/ÎČ or TCRÎł/ÎŽ, and the expression of CD4 and CD8 on CD3<sup>+</sup> cells the bone marrow of NSG mice that were transplanted with AML-MNCs as described in (A) (Within CD3<sup>+</sup> cells: TCRÎł/ÎŽ: 5.0±15.2%, TCRα/ÎČ: 89.2±22.1%; Within TCRα/ÎČ<sup>+</sup> cells: CD4<sup>+</sup> CD8<sup>−</sup>: 66.2±23.6%, CD4<sup>−</sup> CD8<sup>+</sup>: 20.2±19.2%, CD4<sup>+</sup> CD8<sup>+</sup>: 9.3±14.5%.) (C) Plot shows the frequency of indicated VÎČ segments used in human α/ÎČ T cell receptors on T cells in the blood of healthy controls (‘in man’) and in the bone marrow of NSG mice that had received MNCs from AML patients as described in (A, ‘in mice’). Frequencies based on human CD45<sup>+</sup> CD3<sup>+</sup> cells are shown. (D) Bar graph shows the frequency of human T lymphocytes (hCD45<sup>+</sup>CD3<sup>+</sup>) that express CD25 and CD69 in blood, bone marrow and spleen of NSG mice that were transplanted with 10<sup>7</sup> MNCs from AML patients 9.7±2.2 weeks before. N = 53 for all groups. (E) Bar graph shows the frequency of T lymphocytes that express CD25 and CD69 in the peripheral blood (4.7±0.3% of T lymphocytes) and bone marrow (21.9±10.2%) of healthy donors. N = 3 for all groups. (F) Maximum blood chimerism was determined after the transplantation of titrated numbers of CD2<sup>+</sup> T cells that were sorted from the peripheral blood of a healthy donor. Donor-cell chimerism ≄0.1% hCD45<sup>+</sup> (considered T cell engraftment, left y-axis) was reached only if ≄10<sup>5</sup> CD2<sup>+</sup> cells were transplanted. Virtually all engrafted human leukocytes expressed CD3 (% hCD45<sup>+</sup>CD3<sup>+</sup>, right y-axis). Mean and standard deviation are shown. (G) Plot depicts donor-cell chimerism in the bone marrow of NSG recipient mice as described in (D). Mean and standard deviation are shown.</p

    Sublethal irradiation and fresh donor cells reduces survival in NSG mice transplanted with AML-MNCs.

    No full text
    <p>(A) Kaplan-Meyer plot of mice that were transplanted with MNCs of AML patients. NSG mice were transplanted with freshly isolated MNCs with (fresh/irradiated; grey solid line) and without (fresh/non-conditioned; black solid line) previous conditioning, or thawed MNCs with (thawed/irradiated; grey dotted line) or without (thawed/non-conditioned; black dotted line) sublethal irradiation. The percentage of mice transplanted and available for bone marrow analysis is indicated below graph (BM analysis available). Using fresh donor cells and irradiation conditioning shortened the life span of the recipient mice (fresh/irradiated vs fresh/non-conditioned p = 0.007; thawed/irradiated vs thawed/non-conditioned p = 0.018; and fresh/irradiated vs thawed/irradiated p = 0.0054; fresh/non-conditioned vs thawed/non-conditioned p = 0.0051; Gehan-Breslow-Wicoxon Test). Rx = irradiation conditioning. (B) Plot shows the bone marrow chimerism (percentage of human CD45<sup>+</sup> cells of total CD45<sup>+</sup> cells) after the transplantation of AML samples from bone marrow (BM), peripheral blood (PB), and leukapheresis products (LPH) 12–16 weeks before. LPH-MNCs showed a significant increase in the bone marrow overall chimerism compared to BM-MNCs.</p

    Depletion of CD3<sup>+</sup> and CD19<sup>+</sup> cells from the graft prevents xGvHD symptoms, and augments AML engraftment.

    No full text
    <p>Unconditioned NSG mice were transplanted with equal numbers (0.15–0.6×10<sup>7</sup> cells) of thawed MNCs from AML #7–9 (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0060680#pone-0060680-t001" target="_blank">Table 1</a>) with or without previous depletion of CD3<sup>+</sup> and CD19<sup>+</sup> lymphocytes (CD3<sup>−</sup>CD19<sup>−</sup>MNC and MNC, respectively). Mice were sacrificed for bone marrow analysis 12 weeks after transplantation, or when detoriation of health occurred, and analyzed by flow cytometry. AML samples #7–9 showed a common, characteristic phenotype of <i>Npm1</i>-mutated AML with positivity for CD33 and CD117, but lack of CD34 expression. (A) Dot plots show expression of CD3 versus CD33 (left column), CD34 versus CD117 (middle), and side scatter (SSC) versus CD45 (right column) on human CD45<sup>+</sup> MNCs from a healthy donor (top), from AML patient #7 (second row from top), and from the bone marrow of NSG recipient mice that were transplanted with either MNCs (second row from bottom) or CD3<sup>−</sup>CD19<sup>−</sup>MNCs (bottom) from AML #7 twelve weeks before. Data representative for all AML samples #7–9 analyzed. (B-E) Plots show the mean donor-cell chimerism (B, % hCD45<sup>+</sup>; MNC: 33.3±27%, CD3<sup>−</sup>CD19<sup>−</sup>MNC: 22.4±30.9%), the frequency of CD19<sup>+</sup> cells (C, MNC: 18.5±26.0%, CD3<sup>−</sup>CD19<sup>−</sup>MNCs: 12.3±14.3%), or CD3<sup>+</sup> cells (D, MNC: 42.4±43.5%, CD3<sup>−</sup>CD19<sup>−</sup>MNCs: 0.02±0.02%, p = 0.0247), or CD33<sup>+</sup> cells (E, MNC: 35.9±36.3%, CD3<sup>−</sup>CD19<sup>−</sup>MNCs: 85.0±17.8%, p = 0.0087) within donor-derived leukocytes (hCD45<sup>+</sup>) in the bone marrow of recipient mice 6–12 weeks after transplantation with AML-samples #7–9 (MNC: 33.3±27%, CD3<sup>−</sup>CD19<sup>−</sup>MNC: 22.4±30.9%).</p
    corecore