20 research outputs found

    Responsible Leadership in a Stakeholder Society - A Relational Perspective

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    We understand responsible leadership as a social-relational and ethical phenomenon, which occurs in social processes of interaction. While the prevailing leadership literature has for the most part focussed on the relationship between leaders and followers in the organization and defined followers as subordinates, we show in this article that leadership takes place in interaction with a multitude of followers as stakeholders inside and outside the corporation. Using an ethical lens, we discuss leadership responsibilities in a stakeholder society, thereby following Bass and Steidelmeier's suggestion to discuss "leadership in the context of contemporary stakeholder theory” (1999: 200). Moreover, from a relational and stakeholder perspective we approach the questions: What is responsible leadership? What makes a responsible leader? What qualities are needed? Finally, we propose a so-called "roles model” of responsible leadership, which gives a gestalt to a responsible leader and describes the different roles he or she takes in leading stakeholders and business in societ

    Responsible Leadership: Verantwortliche FĂŒhrung im Kontext einer globalen Stakeholder-Gesellschaft

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    "Under the umbrella term ‘Responsible Leadership’ a new research domain has emerged in recent years. It takes on the normative challenges of leading responsibly in a complex and connected global stakeholder society. We introduce ‘Responsible Leadership’ as a timely research domain by discussing, firstly, some of the key challenges leaders face in an environment of contested values. We show, secondly, why traditional leadership research is unable to meet these challenges and thus to provide orienting knowledge on how to lead responsibly. Against this background we introduce, thirdly, some of the key sources on research in ‘Responsible Leadership’ and conclude our article by sketching out perspectives for research in leadership ethics, addressing emerging research needs and vistas." (author's abstract

    Mutations in the histone methyltransferase gene KMT2B cause complex early-onset dystonia.

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    Histone lysine methylation, mediated by mixed-lineage leukemia (MLL) proteins, is now known to be critical in the regulation of gene expression, genomic stability, cell cycle and nuclear architecture. Despite MLL proteins being postulated as essential for normal development, little is known about the specific functions of the different MLL lysine methyltransferases. Here we report heterozygous variants in the gene KMT2B (also known as MLL4) in 27 unrelated individuals with a complex progressive childhood-onset dystonia, often associated with a typical facial appearance and characteristic brain magnetic resonance imaging findings. Over time, the majority of affected individuals developed prominent cervical, cranial and laryngeal dystonia. Marked clinical benefit, including the restoration of independent ambulation in some cases, was observed following deep brain stimulation (DBS). These findings highlight a clinically recognizable and potentially treatable form of genetic dystonia, demonstrating the crucial role of KMT2B in the physiological control of voluntary movement.Funding for the project was provided by the Wellcome Trust for UK10K (WT091310) and DDD Study. The DDD study presents independent research commissioned by the Health Innovation Challenge Fund [grant number HICF-1009-003] - see www.ddduk.org/access.html for full acknowledgement. This work was supported in part by the Intramural Research Program of the National Human Genome Research Institute and the Common Fund, NIH Office of the Director. This work was supported in part by the German Ministry of Research and Education (grant nos. 01GS08160 and 01GS08167; German Mental Retardation Network) as part of the National Genome Research Network to A.R. and D.W. and by the Deutsche Forschungsgemeinschaft (AB393/2-2) to A.R. Brain expression data was provided by the UK Human Brain Expression Consortium (UKBEC), which comprises John A. Hardy, Mina Ryten, Michael Weale, Daniah Trabzuni, Adaikalavan Ramasamy, Colin Smith and Robert Walker, affiliated with UCL Institute of Neurology (J.H., M.R., D.T.), King’s College London (M.R., M.W., A.R.) and the University of Edinburgh (C.S., R.W.)

    31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

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    Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

    Desarrollando lĂ­deres globales responsables

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    Global Governance: CSR and the Role of the UN Global Compact

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    The article discusses the role of the UN Global Compact (UNGC) in the emerging global CSR infrastructure. It evaluates the debate around the effectiveness and legitimacy of the UNGC alongside the arguments of its supporters and critics and thereby introduces the Thematic Symposium contributions. The article further identifies three theoretical perspectives that are used by scholars to discuss the performance of the UNGC: economic, socio-historical, and normative. It proposes that these perspectives can serve as generic distinctions with direct relevance for the evaluation of the UNGC. Once the perspective is chosen, it drives towards a certain purpose which implies assumptions and design features with regard to the UNGC. Finally, the article offers a future research agenda, emphasising the research needed on the UNGC in four areas: the identification of processes and influence mechanisms; legitimacy and effectiveness; local networks and regional development; and the interface of the UNGC and responsible leadership

    Global governance : CSR and the role of the UN Global Compact

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    The article discusses the role of the UN Global Compact (UNGC) in the emerging global CSR infrastructure. It evaluates the debate around the effectiveness and egitimacy of the UNGC alongside the arguments of its supporters and critics and thereby introduces the Thematic Symposium contributions. The article further identifies three theoretical perspectives that are used by scholars to discuss the performance of the UNGC: economic, socio-historical, and normative. It proposes that these perspectives can serve as generic distinctions with direct relevance for the evaluation of the UNGC. Once the perspective is chosen, it drives towards a certain purpose which implies assumptions and design features with regard to the UNGC. Finally, the article offers a future research agenda, emphasising the research needed on the UNGC in four areas: the identification of processes and influence mechanisms; legitimacy and effectiveness; local networks and regional development; and the interface of the UNGC and responsible leadership

    Global governance: CSR and the role of the UN Global Compact

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    The article discusses the role of the UN Global Compact (UNGC) in the emerging global CSR infrastructure. It evaluates the debate around the effectiveness and egitimacy of the UNGC alongside the arguments of its supporters and critics and thereby introduces the Thematic Symposium contributions. The article further identifies three theoretical perspectives that are used by scholars to discuss the performance of the UNGC: economic, socio-historical, and normative. It proposes that these perspectives can serve as generic distinctions with direct relevance for the evaluation of the UNGC. Once the perspective is chosen, it drives towards a certain purpose which implies assumptions and design features with regard to the UNGC. Finally, the article offers a future research agenda, emphasising the research needed on the UNGC in four areas: the identification of processes and influence mechanisms; legitimacy and effectiveness; local networks and regional development; and the interface of the UNGC and responsible leadership

    Responsible Leadership - Verantwortliche Fuehrung im Kontext einer globalen Stakeholder-Gesellschaft

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    Seit wenigen Jahren entsteht unter dem Dachbegriff Responsible Leadership ein neues Forschungsfeld, das sich der normativen Herausforderungen von Fuehrung im Zeitalter der Stakeholder-Gesellschaft in Theorie und Praxis annimmt. Im Mittelpunkt steht die Reflexion auf den normativen Gehalt von Fuehrung und die Generierung von ethischem Orientierungswissen zur Gestaltung einer verantwortlichen Fuehrungspraxis. Nach einer Einfuehrung von Responsible Leadership als ein neues Thema im internationalen Fuehrungsdiskurs werden in diesem Beitrag zunaechst zentrale Herausforderungen verantwortlicher Fuehrung skizziert; anschliessend wird aufgezeigt, warum die bestehende Fuehrungsforschung keine Antworten auf diese Herausforderungen geben kann, der Stand der Forschung zum Thema wiedergegeben und schliesslich Perspektiven fuer eine Fuehrungsforschung benannt, die im Sinne eines umfassenden Verstaendnis von Responsible Leadership zu einem Leitbild verantwortlicher Fuehrung im Zeitalter einer globalen Stakeholder-Gesellschaft beitragen.Responsible Leadership, Leadership Ethics, Stakeholder Theory, Leadership Research, Paradigm Shift
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