PRODUCTION DISTORTIONS IN THE SLOVAKIAN GRAIN SECTOR RESULTING FROM AGRICULTURAL SUBSIDIES

A Policy Analysis Method, based on social benefit-cost analysis, is applied to five production areas of the Slovak Republic to analyze production distortions resulting from direct systematic subsidies in Slovakia. Three grains are analyzed: wheat, barley, and corn. Results indicate that currently applied policies have significant distortion effects, but those effects are not homogeneous across commodities and production areas.Agricultural and Food Policy, Productivity Analysis,

Cohesin mutations alter DNA damage repair and chromatin structure and create therapeutic vulnerabilities in MDS/AML

The cohesin complex plays an essential role in chromosome maintenance and transcriptional regulation. Recurrent somatic mutations in the cohesin complex are frequent genetic drivers in cancer, including myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML). Here, using genetic dependency screens of stromal antigen 2-mutant (STAG2-mutant) AML, we identified DNA damage repair and replication as genetic dependencies in cohesin-mutant cells. We demonstrated increased levels of DNA damage and sensitivity of cohesin-mutant cells to poly(ADP-ribose) polymerase (PARP) inhibition. We developed a mouse model of MDS in which Stag2 mutations arose as clonal secondary lesions in the background of clonal hematopoiesis driven by tet methylcytosine dioxygenase 2 (Tet2) mutations and demonstrated selective depletion of cohesin-mutant cells with PARP inhibition in vivo. Finally, we demonstrated a shift from STAG2- to STAG1-containing cohesin complexes in cohesin-mutant cells, which was associated with longer DNA loop extrusion, more intermixing of chromatin compartments, and increased interaction with PARP and replication protein A complex. Our findings inform the biology and therapeutic opportunities for cohesin-mutant malignancies

Assembling defenses against therapy-resistant leukemic stem cells: Bcl6 joins the ranks

The resistance of leukemic stem cells in response to targeted therapies such as tyrosine kinase inhibitors (TKIs) relies on the cooperative activity of multiple signaling pathways and molecules, including TGFβ, AKT, and FOXO transcription factors (TFs). B cell lymphoma 6 (BCL6) is a transcriptional repressor whose translocation or mutation is associated with diffuse large BCL. New data now show that BCL6 is critical for the maintenance of leukemias driven by the BCR-ABL translocation (Philadelphia chromosome), suggesting that BCL6 is a novel, targetable member of the complex signaling pathways critical for leukemic stem cell survival

A self-organized model for cell-differentiation based on variations of molecular decay rates

Systemic properties of living cells are the result of molecular dynamics governed by so-called genetic regulatory networks (GRN). These networks capture all possible features of cells and are responsible for the immense levels of adaptation characteristic to living systems. At any point in time only small subsets of these networks are active. Any active subset of the GRN leads to the expression of particular sets of molecules (expression modes). The subsets of active networks change over time, leading to the observed complex dynamics of expression patterns. Understanding of this dynamics becomes increasingly important in systems biology and medicine. While the importance of transcription rates and catalytic interactions has been widely recognized in modeling genetic regulatory systems, the understanding of the role of degradation of biochemical agents (mRNA, protein) in regulatory dynamics remains limited. Recent experimental data suggests that there exists a functional relation between mRNA and protein decay rates and expression modes. In this paper we propose a model for the dynamics of successions of sequences of active subnetworks of the GRN. The model is able to reproduce key characteristics of molecular dynamics, including homeostasis, multi-stability, periodic dynamics, alternating activity, differentiability, and self-organized critical dynamics. Moreover the model allows to naturally understand the mechanism behind the relation between decay rates and expression modes. The model explains recent experimental observations that decay-rates (or turnovers) vary between differentiated tissue-classes at a general systemic level and highlights the role of intracellular decay rate control mechanisms in cell differentiation.Comment: 16 pages, 5 figure

A practical and user-friendly toxicity classification system with microbiotests for natural waters and wastewaters

Various types of toxicity classification systems have been elaborated by scientists in different countries, with the aim of attributing a hazard score to polluted environments or toxic waste-waters or of ranking them in accordance with increasing levels of toxicity. All these systems are based on batteries of standard acute toxicity tests (several of them including chronic assays as well) and are therefore dependent on the culturing and maintenance of live stocks of test organisms. Most systems require performance of the bioassays; on dilution series of the original samples, for subsequent calculation of L(E C50 or threshold toxicity values. Given the complexity and costs of these toxicity measurements, they can only be applied in well-equipped and highly specialized laboratories, and none of the classification methods so far has found general acceptance at the international level. The development of microbiotests that are independent of continuous culturing of live organisms has stimulated international collaboration. Coordinated at Ghent University, Belgium, collaboration by research groups from 10 countries in central and eastern Europe resulted in an alternative toxicity classification system that was easier to apply and substantially more cost effective than any of the earlier methods. This new system was developed and applied in the framework of a cooperation agreement between the Flemish community in Belgium and central and eastern Europe. The toxicity classification system is based on a battery of (culture-independent) microbiotests and is particularly suited for routine monitoring. It indeed only requires testing on undiluted samples of natural waters or wastewaters discharged into the aquatic environment, except for wastewaters that demonstrate more than 50% effect. The scoring system ranks the waters or wastewaters in 5 classes of increasing hazard/toxicity, with calculation of a weight factor for the concerned hazard/toxicity class. The new classification system was applied during 2000 by the participating laboratories on samples of river water, groundwaters, drinking waters, mine waters, sediment pore waters, industrial effluents, soil leachates, and waste dump leachates and was found to be easy to apply and reliable. © 2003 Wiley Periodicals, Inc

Core Circadian Clock Genes Regulate Leukemia Stem Cells in AML

Leukemia stem cells (LSCs) have the capacity to self-renew and propagate disease upon serial transplantation in animal models, and elimination of this cell population is required for curative therapies. Here, we describe a series of pooled, in vivo RNAi screens to identify essential transcription factors (TFs) in a murine model of acute myeloid leukemia (AML) with genetically and phenotypically defined LSCs. These screens reveal the heterodimeric, circadian rhythm TFs Clock and Bmal1 as genes required for the growth of AML cells in vitro and in vivo. Disruption of canonical circadian pathway components produces anti-leukemic effects, including impaired proliferation, enhanced myeloid differentiation, and depletion of LSCs. We find that both normal and malignant hematopoietic cells harbor an intact clock with robust circadian oscillations, and genetic knockout models reveal a leukemia-specific dependence on the pathway. Our findings establish a role for the core circadian clock genes in AML.National Institutes of Health (U.S.) (Grant P01 CA066996)National Institutes of Health (U.S.) (Grant R01 HL082945)National Cancer Institute (U.S.) (Grant P30-CA14051

Enactment of compassionate leadership by nursing and midwifery managers: results from an international online survey

Aim To explore the views of an international sample of nursing and midwifery managers concerning attributes that they associate with compassionate management. Method A cross- sectional online survey. Using a snowballing sampling method, 1217 responses were collected from nursing and midwifery managers in 17 countries. A total of complete 933 responses to a question related to which actions and behaviours indicated that a manager was exercising compassionate leadership were analysed for this paper. First, content analysis of the responses was conducted, and second, a relative distribution of the identified themes for the overall sample and for each participating country was calculated. Results Six main themes were identified describing the attributes of a compassionate leader: (1) Virtuous support, (2) Communication, (3) Personal virtues of the manager, (4) Participatory communication, (5) Growth/flourishing/ nurturing and (6) Team cohesion. The first three themes mentioned above collectively accounted for 63% of the responses, and can therefore be considered to be the most important characteristics of compassionate management behaviour. Conclusion The key indicators of compassionate management in nursing and midwifery which were identified emphasise approachability, active and sensitive listening, sympathetic responses to staff members’ difficulties (especially concerning child and other caring responsibilities), active support of and advocacy for the staff team and active problem solving and conflict resolution. While there were differences between the countries’ views on compassionate healthcare management, some themes were widely represented among different countries’ responses, which suggest key indicators of compassionate management that apply across culture

Socially assistive robots in health and social care: acceptance and cultural factors. Results from an exploratory international online survey

Aim: This study explored the views of an international sample of registered nurses and midwives working in health and social care concerning socially assistive robots (SARs), and the relationship between dimensions of culture and rejection of the idea that SARs had benefits in these settings. Methods: An online survey was used to obtain rankings of (among other topics) the extent to which SARs have benefits for health and social care. It also asked for free text responses regarding any concerns about SARs. Results: Most respondents were overwhelmingly positive about SARs' benefits. A small minority strongly rejected this idea, and qualitative analysis of the objections raised by them revealed three major themes: things might go wrong, depersonalization, and patient‐related concerns. However, many participants who were highly accepting of the benefits of SARs expressed similar objections. Cultural dimensions of long‐term orientation and uncertainty avoidance feature prominently in technology acceptance research. Therefore, the relationship between the proportion of respondents from each country who felt that SARs had no benefits and each country's ratings on long‐term orientation and uncertainty avoidance were also examined. A significant positive correlation was found for long‐term orientation, but not for uncertainty avoidance. Conclusion: Most respondents were positive about the benefits of SARs, and similar concerns about their use were expressed both by those who strongly accepted the idea that they had benefits and those who did not. Some evidence was found to suggest that cultural factors were related to rejecting the idea that SARs had benefits

Obstacles to compassion-giving among nursing and midwifery managers: an international study

Aim: To explore nursing and midwifery managers’ views regarding obstacles to compassion-giving across country cultures. Background: The benefit of compassionate leadership is being advocated, but despite the fact that healthcare is invariably conducted within culturally diverse workplaces, the interconnection of culture, compassion and leadership is rarely addressed. Furthermore, evidence on how cultural factors hinder the expression of compassion among nursing and midwifery managers is lacking. Methods: Cross-sectional, exploratory, international online survey involving 1 217 participants from 17 countries. Managers’ responses on open-ended questions related to barriers for providing compassion were entered and thematically analysed through NVivo. Results: Three key themes related to compassion-giving obstacles emerged across countries: 1. related to the managers’ personal characteristics and experiences; 2. system-related; 3. staff-related. Conclusions: Obstacles to compassion-giving among managers vary across countries. An understanding of the variations across countries and cultures of what impedes compassion to flourish in healthcare is important. Implications for nursing practice and policy: Nursing mangers should wisely use their power by adopting leadership styles that promote culturally competent and compassionate workplaces with respect for human rights. Policymakers should identify training and mentoring needs to enable the development of managers’ practical wisdom. Appropriate national and international policies should facilitate the establishment of standards and guidelines for compassionate leadership, in the face of distorted organisational cultures and system-related obstacles to compassion-giving

The importance of being a compassionate leader: the views of nursing and midwifery managers from around the world

Introduction: Despite the importance of compassionate leadership in health care, many of the existing publications do not account for the effect of culture. The aim of this study is to explore the views of nursing and midwifery managers from different countries in relation to the definition, advantages, and importance of compassion. Methodology: A cross-sectional, descriptive, exploratory online survey was conducted across 17 countries, containing both closed and open-ended questions. Data from N = 1,217 respondents were analyzed using a directed hybrid approach focusing only on qualitative questions related to compassion-giving. Results: Four overarching themes capture the study’s results: (1) definition of compassion, (2) advantages and importance of compassion for managers, (3) advantages and importance of compassion for staff and the workplace, and (4) culturally competent and compassionate leadership. Discussion: Innovative research agendas should pursue further local qualitative empirical research to inform models of culturally competent and compassionate leadership helping mangers navigate multiple pressures and be able to transculturally resonate with their staff and patients