Clinical relevance of silent red blood cell autoantibodies.

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Management of chronic lymphocytic leukemia: practice guidelines from the Italian Society of Hematology, the Italian Society of Experimental Hematology and the Italian Group for Bone Marrow Transplantation.

The Italian Society of Hematology (SIE) and two affiliate societies (SIES and GITMO) commissioned a project to develop clinical practice guidelines for the treatment of chronic lymphocytic leukemia (CLL). METHODS: Key questions in the management of patients with CLL were formulated by an Advisory Committee and approved by an Expert Panel of eight senior hematologists. After a systematic review of the literature, recommendations for disease-specific and supportive therapies were formulated and graded according to the supporting evidence. Explicit consensus methods were used for providing recommendations for questions with incomplete or potentially biased evidence. RESULTS: It is recommended that therapy is commenced in patients with CLL when at least one of the following are present: B-symptoms, progressive/obstructive lymphadenopathy or organomegaly, rapid lymphocyte doubling time, anemia or thrombocytopenia (of new onset, worsening or steroid-resistant). It is recommended that patients without co-morbidity should receive fludarabine plus cyclophosphamide, whereas elderly patients with co-morbidity should receive oral chlorambucil. Younger patients with unfavorable biological risk factors should be considered for high-dose chemotherapy and autologous or allogeneic stem cell transplantation within approved clinical trials. Patients either relapsing rapidly after, or non-responsive to, first-line chlorambucil should receive fludarabine-containing regimens. Patients either relapsing soon after or not responding to fludarabine-based chemotherapy should be considered for schedules including non-cross-reactive agents, such as alemtuzumab, possibly followed by high-dose chemotherapy and autologous transplantation in the context of a clinical trial or by allogeneic stem cell transplantation. CONCLUSIONS: We describe the results of a systematic literature review and an explicit approach to consensus techniques which resulted in recommendations for the key therapeutic decisions in patients with CLL

Simple, Fast and Accurate Implementation of the Diffusion Approximation Algorithm for Stochastic Ion Channels with Multiple States

The phenomena that emerge from the interaction of the stochastic opening and closing of ion channels (channel noise) with the non-linear neural dynamics are essential to our understanding of the operation of the nervous system. The effects that channel noise can have on neural dynamics are generally studied using numerical simulations of stochastic models. Algorithms based on discrete Markov Chains (MC) seem to be the most reliable and trustworthy, but even optimized algorithms come with a non-negligible computational cost. Diffusion Approximation (DA) methods use Stochastic Differential Equations (SDE) to approximate the behavior of a number of MCs, considerably speeding up simulation times. However, model comparisons have suggested that DA methods did not lead to the same results as in MC modeling in terms of channel noise statistics and effects on excitability. Recently, it was shown that the difference arose because MCs were modeled with coupled activation subunits, while the DA was modeled using uncoupled activation subunits. Implementations of DA with coupled subunits, in the context of a specific kinetic scheme, yielded similar results to MC. However, it remained unclear how to generalize these implementations to different kinetic schemes, or whether they were faster than MC algorithms. Additionally, a steady state approximation was used for the stochastic terms, which, as we show here, can introduce significant inaccuracies. We derived the SDE explicitly for any given ion channel kinetic scheme. The resulting generic equations were surprisingly simple and interpretable - allowing an easy and efficient DA implementation. The algorithm was tested in a voltage clamp simulation and in two different current clamp simulations, yielding the same results as MC modeling. Also, the simulation efficiency of this DA method demonstrated considerable superiority over MC methods.Comment: 32 text pages, 10 figures, 1 supplementary text + figur

Kawasaki disease : an epidemiological study in central Italy

BACKGROUND: Kawasaki disease (KD) is a systemic vasculitis with an acute and self-limited course. The incidence of KD differs widely among ethnic groups and is higher in the Asian population. In Italy, no recent data are available. Our purpose is to define the epidemiology of Kawasaki disease in the years 2008-2013 in children aged\u2009<\u200914 years in the Italian regions of Tuscany and Emilia Romagna through administrative data. METHODS: We studied the epidemiology of KD in the years 2008-2013 in children 0-14 years old resident in Tuscany and in Emilia Romagna regions using hospital ICD-9 discharge codes with a thorough data cleaning for duplicates. RESULTS: The distribution of the KD patients across ages was similar for the two regions with a peak in the second year of life. When considering data of the two regions together, the rate of incidence was 17.6 for 100,000 children under 5 years. For both Regions the incidence rose slightly during the study period and had a seasonal distribution, with higher incidence in spring and winter. CONCLUSION: This is the first Italian study performed through the use of administrative data. Figures are in line but slightly higher than those published in other European countries

Molecular evolution of HoxA13 and the multiple origins of limbless morphologies in amphibians and reptiles

Developmental processes and their results, morphological characters, are inherited through transmission of genes regulating development. While there is ample evidence that cis-regulatory elements tend to be modular, with sequence segments dedicated to different roles, the situation for proteins is less clear, being particularly complex for transcription factors with multiple functions. Some motifs mediating protein-protein interactions may be exclusive to particular developmental roles, but it is also possible that motifs are mostly shared among different processes. Here we focus on HoxA13, a protein essential for limb development. We asked whether the HoxA13 amino acid sequence evolved similarly in three limbless clades: Gymnophiona, Amphisbaenia and Serpentes. We explored variation in ω (dN/dS) using a maximum-likelihood framework and HoxA13sequences from 47 species. Comparisons of evolutionary models provided low ω global values and no evidence that HoxA13 experienced relaxed selection in limbless clades. Branch-site models failed to detect evidence for positive selection acting on any site along branches of Amphisbaena and Gymnophiona, while three sites were identified in Serpentes. Examination of alignments did not reveal consistent sequence differences between limbed and limbless species. We conclude that HoxA13 has no modules exclusive to limb development, which may be explained by its involvement in multiple developmental processes

High-resolution Extinction Map in the Direction of the Strongly Obscured Bulge Fossil Fragment Liller 1*

We used optical images acquired with the Wide Field Camera of the Advanced Camera for Surveys on board the Hubble Space Telescope and near-infrared data from Gemini Multi-conjugate Adaptive Optics System (GeMS)/Gemini South Adaptive Optics Imager (GSAOI) to construct a high-resolution extinction map in the direction of the bulge stellar system Liller 1. In spite of its appearance of a globular cluster, Liller 1 has been recently found to harbor two stellar populations with remarkably different ages, and it is the second complex stellar system with similar properties (after Terzan 5) discovered in the bulge, thus defining a new class of objects: the Bulge Fossil Fragments. Because of its location in the inner bulge of the Milky Way, very close to the Galactic plane, Liller 1 is strongly affected by large and variable extinction. The simultaneous study of both the optical and the near-infrared color–magnitude diagrams revealed that the extinction coefficient RV in the direction of Liller 1 has a much smaller value than commonly assumed for diffuse interstellar medium (RV = 2.5, instead of 3.1), in agreement with previous findings along different light paths to the Galactic bulge. The derived differential reddening map has a spatial resolution ranging from 1'' to 3'' over a field of view of about 90'' × 90''. We found that the absorption clouds show patchy substructures with extinction variations as large as δE(B − V) ∼ 0.9 mag