Summary:We investigated the use of 'prophylactic' donor lymphocyte infusions (DLI) containing 1 ؋ 10 7 CD3 ؉ cells, given at 30, 60 and 90 days post-allogeneic blood and marrow transplantation (BMT), following conditioning with fludarabine 30 mg/m 2 /4 days and melphalan 70 mg/m 2 /2 days. GVHD prophylaxis consisted of cyclosporin A (CsA) 2 mg/kg daily with early tapering by day 60. Our goals were the rapid achievement of chimerism and disease control, providing an immunological platform for DLIs to treat refractory patients with hematological malignancies. Twelve heavily pre-treated patients with life expectancy less than 6 months were studied; none were in remission. Diagnoses were AML (n ‫؍‬ 4), MDS (n ‫؍‬ 1), ALL (n ‫؍‬ 3), CML (n ‫؍‬ 3) and multiple myeloma (n ‫؍‬ 1). Response rate was 75%. Three patients are alive at a median of 450 days (range, 450-540). Two patients are in remission of CML in blast crisis and AML for more than 14 months. Median survival is 116 days (range, 25-648). Six patients received 12 DLIs; three patients developed acute GVHD after the first infusion and were excluded from further DLIs, but no GVHD occurred among patients receiving subsequent DLIs. One patient with CML in blast crisis went into CR after the first DLI. The overall incidence of acute GVHD was 70%. Primary causes of death were infections (n ‫؍‬ 3), acute GVHD (n ‫؍‬ 3), chronic GVHD (n ‫؍‬ 1) and disease relapse (n ‫؍‬ 2). We observed high response and chimerism rates at the expense of an excessive incidence of GVHD. DLI given at day ؉30 post BMT caused GVHD in 50% of the patients, and its role in this setting remains unclear. The therapeutic benefit of allogeneic BMT is in part related to an immunological graft-versus-leukemia (GVL) effect that frequently evolves in the context of graft-versus-host disease (GVHD). The ability of donor lymphocytes to induce remission in patients relapsing after allogeneic transplantation illustrates the potency of this effect.1 Establishing donor-recipient tolerance with less toxic regimens may provide the basis for further immunological manipulations in order to maximize the GVL effect. However, rapidly evolving diseases may not be amenable to this strategy, considering that the immune-mediated elimination of malignant cells may take weeks or months to occur. This fact suggests the need for strategies to reinforce the immune-mediated phenomena in the post-transplant period.Groups in Jerusalem and Houston pioneered the use of sub-lethal doses of fludarabine-based conditioning regimens. These regimens have been shown to be less toxic and to provide enough immunosuppression to prevent graft rejection and establish stable mixed or complete chimerism.2,3 The combination of melphalan and fludarabine has enabled allogeneic stem cell engraftment in the majority of patients treated, at least in the setting of HLA-identical transplantation. Patients with refractory relapses of advanced leukemias appear to benefit the least.

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Entropy is a concept that emerged in the 19th century. It used to be associated with heat harnessed by a thermal machine to perform work during the Industrial Revolution. However, there was an unprecedented scientific revolution in the 20th century due to one of its most essential innovations, i.e., the information theory, which also encompasses the concept of entropy. Therefore, the following question is naturally raised: “what is the difference, if any, between concepts of entropy in each field of knowledge?” There are misconceptions, as there have been multiple attempts to conciliate the entropy of thermodynamics with that of information theory. Entropy is most commonly defined as “disorder”, although it is not a good analogy since “order” is a subjective human concept, and “disorder” cannot always be obtained from entropy. Therefore, this paper presents a historical background on the evolution of the term “entropy”, and provides mathematical evidence and logical arguments regarding its interconnection in various scientific areas, with the objective of providing a theoretical review and reference material for a broad audience.

Resistance to thermal shock damage is an important characteristic in refractory materials, since it determines their performance and service life in many applications. Therefore, the use of more sensitive techniques is desirable to improve the evaluation of thermal shock damage and monitoring of nucleation and propagation cracks and microcracks.The aim of this work was to evaluate the potential of damping change characterization to quantify thermal shock damage and to estimate the retained mechanical strength in complement to the dynamic Young's modulus test. Variations in damping and retained Young's modulus and their correlation with the mechanical strength of a high alumina refractory castable were evaluated at different thermal shock temperatures and number of cycles. The changes in damping were proportional to the retained mechanical strength, similarly to the retained Young's modulus. Changes in damping were also detected which were not indicated by the Young's modulus measurements.

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Epilepsy is one of the most common neurological disorders worldwide. Recent findings suggest that the brain is a complex system composed of a network of neurons, and seizure is considered an emergent property resulting from its interactions. Based on this perspective, network physiology has emerged as a promising approach to explore how brain areas coordinate, synchronize and integrate their dynamics, both under perfect health and critical illness conditions. Therefore, the objective of this paper is to present an application of (Dynamic) Bayesian Networks (DBN) to model Local Field Potentials (LFP) data on rats induced to epileptic seizures based on the number of arcs found using threshold analytics. Results showed that DBN analysis captured the dynamic nature of brain connectivity across ictogenesis and a significant correlation with neurobiology derived from pioneering studies employing techniques of pharmacological manipulation, lesion, and modern optogenetics. The arcs evaluated under the proposed approach achieved consistent results based on previous literature, in addition to demonstrating robustness regarding functional connectivity analysis. Moreover, it provided fascinating and novel insights, such as discontinuity between forelimb clonus and generalized tonic-clonic seizure (GTCS) dynamics. Thus, DBN coupled with threshold analytics may be an excellent tool for investigating brain circuitry and their dynamical interplay, both in homeostasis and dysfunction conditions.

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