Enasidenib in the treatment of relapsed/refractory acute myeloid leukemia: an evidence-based review of its place in therapy.

Introduction: Acute myeloid leukemia (AML) remains a disease with high mortality, especially for older patients and those with relapsed/refractory (R/R) disease. With recent advances in molecular testing, targeting particular leukemogenic mutations such as those occurring in isocitrate dehydrogenase (IDH) became possible. Enasidenib is a new small-molecule inhibitor of mutant isocitrate dehydrogenase-2 (IDH2). Aim: The objective of this article is to review the evidence for the use of enasidenib in R/R AML, as well as to outline future directions of enasidenib therapy. Evidence Review: Enasidenib was approved in August 2017, after a successful Phase I/II trial showing an overall response rate (ORR) of 40.3% in R/R disease, with 19.3% of patients achieving complete remission (CR). Enrollees in the trial were mostly older adults. The most prominent toxicities were hyperbilirubinemia and IDH-differentiation syndrome (IDH-DS), though the drug was generally well tolerated and the maximum tolerated dose was not reached. A Phase III trial is currently ongoing. Conclusion: Enasidenib provides a new therapeutic option for patients with R/R AML. Further studies are ongoing to ascertain its role in combination with other agents and newly diagnosed disease

On Morals, Markets, and Climate Change: Exploring Pope Francis’ Challenge

The relation between Culture and Business has caught researchers’ attention long ago; itis not hard to find studies relating to these topics. According to Hofstede et al. (2010, p.18), Hampden-Turner and Trompenaars (2012, p. 8), and Erez and Gati (2004, p. 5),culture can be defined in many levels, for example, organizational culture, and national culture. The field of Business also contains several disciplines, for example, International Business Management, Project Management, and Project Governance. However, not somany studies can be found studying the relation between National Culture and Project Governance; therefore, this study is focused on this relation.This study is designed following a qualitative approach in order to clarify the relation between National Culture and Project Governance Principles. Case studies are used targeting the IT industry of three countries, Spain, Sweden, and Taiwan. These cases also contain the classical theory of cultural dimensions from Hofstede. Hofstede’s dimensionsare Power Distance (PDI), Individualism vs. Collectivism (IDV), Uncertainty Avoidance(UAI), Masculinity vs. Femininity (MAS), Long-term Orientation (LTO), and Indulgencevs. Restraint (IDU). They are applied in this study for distinguishing the differences between countries. This study is also based on the definition of Project GovernancePrinciples from Garland (2009), Klakegg (2008), and Müller et al. (2013). ProjectGovernance Principles are split into two categories as well, hard/ structural principles andsoft/ behaviour principles.In order to clarify the link between National Culture and Project Governance Principles,this thesis’ authors interviewed 19 people, including 10 project managers and 9 experts.All of them have a long experience dealing with Project Management in the three selected countries. Their answers are based on the knowledge and experience of Project Management and Project Governance, as well as their opinions about their own national culture. After analysing the interviews, the authors consider that differences between these three countries in Project Governance and Project Governance Principles do exist. On the other hand, there are also some similar parts, for example, the influence ofcustomers’ orientation and preference. Moreover, respondents, Project Managers and Experts, all mentioned it is also necessary to be aware of the globalized environment, inother words, there is no influence of a single national culture in one country anymore.However, they all admit the importance of their own national culture as well. All these findings from this study encourage further and deeper study in the future

Acquired Elliptocytosis as a Manifestation of Myelodysplastic Syndrome with Ring Sideroblasts and Multilineage Dysplasia.

Acquired elliptocytosis is a known but rarely described abnormality in the myelodysplastic syndromes (MDS). Here we report the case of an elderly male who was admitted to the hospital with chest pain, dyspnea, and fatigue and was found to be anemic with an elliptocytosis that had only recently been noted on peripheral smears of his blood. After bone marrow biopsy he was diagnosed with MDS with ring sideroblasts and multilineage dysplasia and acquired elliptocytosis. Here we report a rare case of acquired elliptocytosis cooccurring with MDS with ring sideroblasts and multilineage dysplasia

A Nonclassical Dihydrogen Adduct of S = ½ Fe(I)

We have exploited the capacity of the “(SiP^(iPr)_3)Fe(I)” scaffold to accommodate additional axial ligands and characterized the mononuclear S = 1/2 H_2 adduct complex (SiP^(iPr)_3)Fe^I(H_2). EPR and ENDOR data, in the context of X-ray structural results, revealed that this complex provides a highly unusual example of an open-shell metal complex that binds dihydrogen as a ligand. The H2 ligand at 2 K dynamically reorients within the ligand-binding pocket, tunneling among the energy minima created by strong interactions with the three Fe–P bonds

Design Research Practice: A Product Semantics Interpretation

In this paper, we adopt a somewhat novel perspective on design research. The concept of product semantics and its focus on meaning is used to interpret design research as design. It is argued that we may conceive of design research as design in two realms: The practical and the academic. In doing design research, there is a reciprocal shaping of artifacts: Better artifacts (contributions to practice) through appropriation of knowledge and methods from the academic realm, and better knowledge artifacts (contributions to academia) by drawing relevance and experiences of appropriation from the practical realm. We adopt a product semantics view to discuss research as design. Product semantics highlights the meaning of artifacts with respect to their (i) stakeholders, (ii) artifacts-in-use, (iii), artifacts-in-language, (iv) artifact lifecycle, and (v) ecology. Based on this interpretation, we propose important activities that should characterize the practice of doing design research

Ancient Water Harvesting Methods in the Drylands of the Mediterranean and Western Asia

Water harvesting methods were a vital part of the water supply system of many ancient settlements in the drylands of the Mediterranean region andWestern Asia. Various water harvesting techniques evolved during the Bronze Age or earlier, and some of these remain in use even today. Based on literature we give a brief overview and present a tentative classification of these water harvesting methods and present the basic concepts behind these techniques supplemented with references to archaeological case studies

Multi-directional sorting modes in deterministic lateral displacement devices

Deterministic lateral displacement (DLD) devices separate micrometer-scale particles in solution based on their size using a laminar microfluidic flow in an array of obstacles. We investigate array geometries with rational row-shift fractions in DLD devices by use of a simple model including both advection and diffusion. Our model predicts novel multi-directional sorting modes that could be experimentally tested in high-throughput DLD devices containing obstacles that are much smaller than the separation between obstacles