Overview of guidelines on iron chelation therapy in patients with myelodysplastic syndromes and transfusional iron overload

Between 2002 and 2008, a number of consensus statements and guidelines were developed by various groups around the world to educate healthcare professionals on the treatment of myelodysplastic syndromes (MDS), including the management of transfusional iron overload with iron chelation therapy. Guidelines have been developed by The Italian Society of Hematology, The UK MDS Guidelines Group, The Nagasaki Group, The National Comprehensive Cancer Network, and The MDS Foundation. These guidelines show that the approaches to managing iron overload in patients with MDS are region specific, differing in their recommendations for when iron chelation therapy should be initiated and strategies for the ongoing management of iron overload. The guidelines all agree that red blood cell transfusions are clinically beneficial to treat the symptomatic anemia in MDS, and that patients with low-risk MDS receiving transfusions are the most likely to benefit from iron chelation therapy

A Texture Bestiary

Textures are topologically nontrivial field configurations which can exist in a field theory in which a global symmetry group $G$ is broken to a subgroup $H$, if the third homotopy group \p3 of $G/H$ is nontrivial. We compute this group for a variety of choices of $G$ and $H$, revealing what symmetry breaking patterns can lead to texture. We also comment on the construction of texture configurations in the different models.Comment: 34 pages, plain Tex. (Minor corrections to an old paper.

Sisyphus cooling and amplification by a superconducting qubit

Laser cooling of the atomic motion paved the way for remarkable achievements in the fields of quantum optics and atomic physics, including Bose-Einstein condensation and the trapping of atoms in optical lattices. More recently superconducting qubits were shown to act as artificial two-level atoms, displaying Rabi oscillations, Ramsey fringes, and further quantum effects. Coupling such qubits to resonators brought the superconducting circuits into the realm of quantum electrodynamics (circuit QED). It opened the perspective to use superconducting qubits as micro-coolers or to create a population inversion in the qubit to induce lasing behavior of the resonator. Furthering these analogies between quantum optical and superconducting systems we demonstrate here Sisyphus cooling of a low frequency LC oscillator coupled to a near-resonantly driven superconducting qubit. In the quantum optics setup the mechanical degrees of freedom of an atom are cooled by laser driving the atom's electronic degrees of freedom. Here the roles of the two degrees of freedom are played by the LC circuit and the qubit's levels, respectively. We also demonstrate the counterpart of the Sisyphus cooling, namely Sisyphus amplification. Parallel to the experimental demonstration we analyze the system theoretically and find quantitative agreement, which supports the interpretation and allows us to estimate system parameters.Comment: 7 pages, 4 figure

Branding the City: The Democratic Legitimacy of a New Mode of Governance

__Abstract__ Place branding has been used to influence ideas concerning communities and districts, especially in regeneration programmes. This article approaches branding as a new governance strategy for managing perceptions. Considering the popular criticism that branding is a form of spin that prevents the public from gaining a proper understanding of their government's policies, this article focuses on the democratic legitimacy of branding in urban governance. The branding of two urban communities in the Netherlands is examined empirically in terms of input legitimacy, throughput legitimacy and output legitimacy. The research shows how the democratic legitimacy of branding varies in the two cases. In one case, branding largely excluded citizens, whereas in the other case there was limited citizen participation. The article indicates that, although branding can potentially be a participatory process in which the feelings and emotions of citizens are included, this potential is not always fully realised in practice

Extensive myocardial infiltration by hemopoietic precursors in a patient with myelodysplastic syndrome

BACKGROUND: Although myocardial infiltration with leukemic blasts is a known finding in patients with acute leukemia, this phenomenon in myelodysplasia is not reported in the literature. Cardiac symptoms in patients with myelodysplasia are often due to anemia and may be due to iron overload and side effects of therapy. CASE PRESENTATION: Herein we report the first case of neoplastic infiltration of the heart with associated myocardial necrosis in a patient with myelodysplasia. It was associated with unicellular and multifocal geographic areas of necrosis in the left ventricle and the interventricular septum. It is likely that cardiac compromise in our patient was due to a combination of restrictive cardiomyopathy due to leukemic infiltration, concomitant anemia, cardiac dilatation, conduction blocks and myocardial necrosis. Myocardial necrosis was most likely due to a combination of ischemic damage secondary to anemia and prolonged hypotension and extensive leukemic infiltration. Markedly rapid decrease in ejection fraction from 66% to 33% also suggests the role of ischemia, since leukemic infiltration is not expected to cause this degree of systolic dysfunction over a 24-hour period. The diagnosis was not suspected during life due to concomitant signs and symptoms of anemia, pulmonary infections, and pericardial and pleural effusions. The patient succumbed to cardiac failure. CONCLUSION: Hemopoietic cell infiltration was not considered in the differential diagnosis and contributed to this patient's morbidity and mortality. This case highlights the clinical importance of considering myocardial infiltration in patients with myelodysplasia and cardiac symptoms

Review of interventions to encourage SMEs to make environmental improvements

Small and medium-sized enterprises (SMEs) are an important part of the world economy but they are thought to be responsible for around 60% of all carbon dioxide emissions and 70% of all pollution. SMEs often have major problems with limited resources, limited knowledge, and limited technical capabilities to deal with their own negative environmental impact. SMEs exhibit widely differing characteristics and commitment where environmental issues are concerned. Yet under these conditions they are all expected to engage in environmental improvement. Interventions that encourage environmental improvement are often polarised between regulation and legislation at one extreme and voluntary environmental agreement at the other. It is clear that a holistic mixture of interventions is necessary to achieve maximum engagement and environmental improvement by all SMEs. In this paper we categorise the different levels of environmental commitment observed in SMEs and develop a selection or &lsquo;toolkit&rsquo; of intervention strategies that might be deployed within each category of SME.<br /

Phosphoproteomic differences in major depressive disorder postmortem brains indicate effects on synaptic function

There is still a lack in the molecular comprehension of major depressive disorder (MDD) although this condition affects approximately 10% of the world population. Protein phosphorylation is a posttranslational modification that regulates approximately one-third of the human proteins involved in a range of cellular and biological processes such as cellular signaling. Whereas phosphoproteome studies have been carried out extensively in cancer research, few such investigations have been carried out in studies of psychiatric disorders. Here, we present a comparative phosphoproteome analysis of postmortem dorsolateral prefrontal cortex tissues from 24 MDD patients and 12 control donors. Tissue extracts were analyzed using liquid chromatography mass spectrometry in a data-independent manner (LC-MSE). Our analyses resulted in the identification of 5,195 phosphopeptides, corresponding to 802 non-redundant proteins. Ninety of these proteins showed differential levels of phosphorylation in tissues from MDD subjects compared to controls, being 20 differentially phosphorylated in at least 2 peptides. The majority of these phosphorylated proteins were associated with synaptic transmission and cellular architecture not only pointing out potential biomarker candidates but mainly shedding light to the comprehension of MDD pathobiology

Proposed diagnostic criteria for classical CMML, CMML variants and pre-CMML conditions

Chronic myelomonocytic leukemia (CMML) is a myeloid neoplasm characterized by dysplasia, abnormal production and accumulation of monocytic cells and an elevated risk to transform into acute leukemia. Over the past two decades, our knowledge about the pathogenesis and molecular mechanisms in CMML has increased substantially. In parallel, better diagnostic criteria and therapeutic strategies have been developed. However, many questions remain regarding prognostication and optimal therapy. In addition, there is a need to define potential pre-phases of CMML and special CMML variants, and to separate these entities from each other and from conditions mimicking CMML. To address these unmet needs, an international consensus group met in a Working Conference in August 2018 and discussed open questions and issues around CMML, its variants, and pre-CMML conditions. The outcomes of this meeting are summarized herein and include diagnostic criteria and a proposed classification of pre-CMML conditions as well as refined minimal diagnostic criteria for classical CMML and special CMML variants, including oligomonocytic CMML and CMML associated with systemic mastocytosis. Moreover, we propose diagnostic standards and tools to delineate between normal, pre-CMML and CMML entities. These criteria and standards should facilitate diagnostic and prognostic evaluations in daily practice and clinical studies in applied hematology