Is flood defense changing in nature? Shifts in the flood defense strategy in six European countries

In many countries, flood defense has historically formed the core of flood risk management but this strategy is now evolving with the changing approach to risk management. This paper focuses on the neglected analysis of institutional changes within the flood defense strategies formulated and implemented in six European countries (Belgium, England, France, the Netherlands, Poland, and Sweden). The evolutions within the defense strategy over the last 30 years have been analyzed with the help of three mainstream institutional theories: a policy dynamics-oriented framework, a structure-oriented institutional theory on path dependency, and a policy actors-oriented analysis called the advocacy coalitions framework. We characterize the stability and evolution of the trends that affect the defense strategy in the six countries through four dimensions of a policy arrangement approach: actors, rules, resources, and discourses. We ask whether the strategy itself is changing radically, i.e., toward a discontinuous situation, and whether the processes of change are more incremental or radical. Our findings indicate that in the European countries studied, the position of defense strategy is continuous, as the classical role of flood defense remains dominant. With changing approaches to risk, integrated risk management, climate change, urban growth, participation in governance, and socioeconomic challenges, the flood defense strategy is increasingly under pressure to change. However, these changes can be defined as part of an adaptation of the defense strategy rather than as a real change in the nature of flood risk management

Étudier le théâtre, dans le monde

Depuis une vingtaine d'années, le champ des études et de la pratique théâtrales à l'Université connaît une progression constante et une formidable diversification. Les programmes se sont multipliés et ouverts à de nouveaux types d'activités, souvent multidisciplinaires, abordant autant la théorie que la création, la formation que la pédagogie. Ce développement se double d'un autre phénomène tout aussi marquant : l'accroissement considérable des compagnies et des rencontres théâtrales universi..

Governance strategies for improving flood resilience in the face of climate change

Flooding is the most common of all natural disasters and accounts for large numbers of casualties and a high amount of economic damage worldwide. To be ‘flood resilient’, countries should have sufficient capacity to resist, the capacity to absorb and recover, and the capacity to transform and adapt. Based on international comparative research, we conclude that six key governance strategies will enhance ‘flood resilience’ and will secure the necessary capacities. These strategies pertain to: (i) the diversification of flood risk management approaches; (ii) the alignment of flood risk management approaches to overcome fragmentation; (iii) the involvement, cooperation, and alignment of both public and private actors in flood risk management; (iv) the presence of adequate formal rules that balance legal certainty and flexibility; (v) the assurance of sufficient financial and other types of resources; (vi) the adoption of normative principles that adequately deal with distributional effects. These governance strategies appear to be relevant across different physical and institutional contexts. The findings may also hold valuable lessons for the governance of climate adaptation more generally

Toward more flood resilience: is a diversification of flood risk management strategies the way forward?

European countries face increasing flood risks due to urbanization, increase of exposure and damage potential, and the effects of climate change. In literature and in practice, it is argued that a diversification of strategies for flood risk management (FRM) - including flood risk prevention (through pro-active spatial planning), flood defense, flood risk mitigation, flood preparation and flood recovery - makes countries more flood resilient. While this thesis is plausible, it should still be empirically scrutinized. This paper aims to do this. Drawing on existing literature we operationalize the notion of "flood resilience" into three capacities: capacity to resist; capacity to absorb and recover; and capacity to transform and adapt. Based on findings from the EU FP7 project STAR-FLOOD, we explore the degree of diversification of FRM strategies and related flood risk governance arrangements at the national level in Belgium, England, France, The Netherlands, Poland and Sweden, as well as these countries' achievement in terms of the three capacities. We found that The Netherlands and to a lesser extent Belgium have a strong "capacity to resist", France a strong "capacity to absorb and recover" and especially England a high capacity to transform and adapt. Having a diverse portfolio of FRM strategies in place may be conducive to high achievements related to the capacities to absorb/recover and to transform and adapt. Hence, we conclude that diversification of FRM strategies contributes to resilience. However, the diversification thesis should be nuanced in the sense that there are different ways to be resilient. First, the three capacities imply different rationales and normative starting points for flood risk governance, the choice between which is inherently political. Second, we found trade-offs between the three capacities, e.g. being resistant seems to lower the possibility to be absorbent. Third, to explain countries' achievements in terms of resilience, the strategies' feasibility in specific physical circumstances and their fit in existing institutional contexts (appropriateness) as well as the establishment of links between strategies, through bridging mechanisms, have also been shown to be crucial factors. The paper provides much needed reflection on the implications of this diagnosis for governments, private parties and citizens who want to increase flood resilience

Toward more flood resilience: is a diversification of flood risk management strategies the way forward?

European countries face increasing flood risks due to urbanization, increase of exposure and damage potential, and the effects of climate change. In literature and in practice, it is argued that a diversification of strategies for flood risk management (FRM) - including flood risk prevention (through pro-active spatial planning), flood defense, flood risk mitigation, flood preparation and flood recovery - makes countries more flood resilient. While this thesis is plausible, it should still be empirically scrutinized. This paper aims to do this. Drawing on existing literature we operationalize the notion of "flood resilience" into three capacities: capacity to resist; capacity to absorb and recover; and capacity to transform and adapt. Based on findings from the EU FP7 project STAR-FLOOD, we explore the degree of diversification of FRM strategies and related flood risk governance arrangements at the national level in Belgium, England, France, The Netherlands, Poland and Sweden, as well as these countries' achievement in terms of the three capacities. We found that The Netherlands and to a lesser extent Belgium have a strong "capacity to resist", France a strong "capacity to absorb and recover" and especially England a high capacity to transform and adapt. Having a diverse portfolio of FRM strategies in place may be conducive to high achievements related to the capacities to absorb/recover and to transform and adapt. Hence, we conclude that diversification of FRM strategies contributes to resilience. However, the diversification thesis should be nuanced in the sense that there are different ways to be resilient. First, the three capacities imply different rationales and normative starting points for flood risk governance, the choice between which is inherently political. Second, we found trade-offs between the three capacities, e.g. being resistant seems to lower the possibility to be absorbent. Third, to explain countries' achievements in terms of resilience, the strategies' feasibility in specific physical circumstances and their fit in existing institutional contexts (appropriateness) as well as the establishment of links between strategies, through bridging mechanisms, have also been shown to be crucial factors. The paper provides much needed reflection on the implications of this diagnosis for governments, private parties and citizens who want to increase flood resilience

A robust and rapid xenograft model to assess efficacy of chemotherapeutic agents for human acute myeloid leukemia

International audienceRelevant preclinical mouse models are crucial to screen new therapeutic agents for acute myeloid leukemia (AML). Current in vivo models based on the use of patient samples are not easy to establish and manipulate in the laboratory. Our objective was to develop robust xenograft models of human AML using well-characterized cell lines as a more accessible and faster alternative to those incorporating the use of patient-derived AML cells. Five widely used AML cell lines representing various AML subtypes were transplanted and expanded into highly immunodeficient non-obese diabetic/LtSz-severe combined immunodeficiency IL2R gamma(null)(c) mice (for example, cell line-derived xenografts). We show here that bone marrow sublethal conditioning with busulfan or irradiation has equal efficiency for the xenotransplantation of AML cell lines. Although higher number of injected AML cells did not change tumor engraftment in bone marrow and spleen, it significantly reduced the overall survival in mice for all tested AML cell lines. On the basis of AML cell characteristics, these models also exhibited a broad range of overall mouse survival, engraftment, tissue infiltration and aggressiveness. Thus, we have established a robust, rapid and straightforward in vivo model based on engraftment behavior of AML cell lines, all vital prerequisites for testing new therapeutic agents in preclinical studies

An In Vivo CRISPR Screening Platform for Prioritizing Therapeutic Targets in AML

CRISPR-Cas9-based genetic screens have successfully identified cell type-dependent liabilities in cancer, including acute myeloid leukemia (AML), a devastating hematologic malignancy with poor overall survival. Because most of these screens have been performed in vitro using established cell lines, evaluating the physiologic relevance of these targets is critical. We have established a CRISPR screening approach using orthotopic xenograft models to validate and prioritize AML-enriched dependencies in vivo, including in CRISPR-competent AML patient-derived xenograft (PDX) models tractable for genome editing. Our integrated pipeline has revealed several targets with translational value, including SLC5A3 as a metabolic vulnerability for AML addicted to exogenous myo-inositol and MARCH5 as a critical guardian to prevent apoptosis in AML. MARCH5 repression enhanced the efficacy of BCL2 inhibitors such as venetoclax, further highlighting the clinical potential of targeting MARCH5 in AML. Our study provides a valuable strategy for discovery and prioritization of new candidate AML therapeutic targets. SIGNIFICANCE: There is an unmet need to improve the clinical outcome of AML. We developed an integrated in vivo screening approach to prioritize and validate AML dependencies with high translational potential. We identified SLC5A3 as a metabolic vulnerability and MARCH5 as a critical apoptosis regulator in AML, both of which represent novel therapeutic opportunities.This article is highlighted in the In This Issue feature, p. 275

Epitope-engineered human hematopoietic stem cells are shielded from CD123-targeted immunotherapy

Targeted eradication of transformed or otherwise dysregulated cells using monoclonal antibodies (mAb), antibody-drug conjugates (ADC), T cell engagers (TCE), or chimeric antigen receptor (CAR) cells is very effective for hematologic diseases. Unlike the breakthrough progress achieved for B cell malignancies, there is a pressing need to find suitable antigens for myeloid malignancies. CD123, the interleukin-3 (IL-3) receptor alpha-chain, is highly expressed in various hematological malignancies, including acute myeloid leukemia (AML). However, shared CD123 expression on healthy hematopoietic stem and progenitor cells (HSPCs) bears the risk for myelotoxicity. We demonstrate that epitope-engineered HSPCs were shielded from CD123-targeted immunotherapy but remained functional, while CD123-deficient HSPCs displayed a competitive disadvantage. Transplantation of genome-edited HSPCs could enable tumor-selective targeted immunotherapy while rebuilding a fully functional hematopoietic system. We envision that this approach is broadly applicable to other targets and cells, could render hitherto undruggable targets accessible to immunotherapy, and will allow continued posttransplant therapy, for instance, to treat minimal residual disease (MRD)