Defective iron supply for erythropoiesis and adequate endogenous erythropoietin production in the anemia associated with systemic-onset juvenile chronic arthritis.

peer reviewedSystemic-onset juvenile chronic arthritis (SoJCA) is associated with high levels of circulating interleukin-6 (IL-6) and is frequently complicated by severe microcytic anemia whose pathogenesis is unclear. Therefore, we studied 20 consecutive SoJCA patients with hemoglobin (Hb) levels <12 g/dL, evaluating erythroid progenitor proliferation, endogenous erythropoietin production, body iron status, and iron supply for erythropoiesis. Hb concentrations ranged from 6.5 to 11.9 g/dL. Hb level was directly related to mean corpuscular volume (r = .82, P < .001) and inversely related to circulating transferrin receptor (r = -.81, P < .001) suggesting that the severity of anemia was directly proportional to the degree of iron-deficient erythropoiesis. Serum ferritin ranged from 18 to 1,660 microgram/L and was unrelated to Hb level. Bone marrow iron stores wore markedly reduced in the three children investigated, and they also showed increased serum transferrin receptor and normal-to-high serum ferritin. All 20 patients had elevated IL-6 levels and normal in vitro growth of erythroid progenitors. Endogenous erythropoietin (epo) production was appropriate for the degree of anemia as judged by both the observed to predicted log (serum epo) ratio 10.95 +/- 0.12) and a comparison of the serum epo-Hb regression found in these subjects with that of thalassemia patients. Multiple regression analysis showed that serum transferrin receptor was the parameter most closely related to hemoglobin concentration: variation in circulating transferrin receptor explained 61% of the variation in Hb level (P < .001). In 10 severely anemic patients, amelioration of anemia following intravenous iron administration resulted in normalization of serum transferrin receptor. Defective iron supply to the erythron rather than blunted epo production is the major cause of the microcytic anemia associated with SoJCA. A true body-iron deficiency caused by decreased iron absorption likely complicates long-lasting inflammation in the most anemic children, and this can be recognized by high serum transferrin receptor levels. Although oral iron is of no benefit, intravenous iron saccharate is a safe and effective means for improving iron availability for erythropoiesis and correcting this anemia. Thus, while chronically high endogenous IL-6 levels do not appear to blunt epo production, they are probably responsible for the observed abnormalities in iron metabolism. Anemia of chronic disease encompasses a variety of anemic conditions whose peculiar features may specifically correlate with the type of cytokine(s) predominantly released

Quantifying the Loss of Coral from a Bleaching Event Using Underwater Photogrammetry and AI-Assisted Image Segmentation

Detecting the impacts of natural and anthropogenic disturbances that cause declines in organisms or changes in community composition has long been a focus of ecology. However, a tradeoff often exists between the spatial extent over which relevant data can be collected, and the resolution of those data. Recent advances in underwater photogrammetry, as well as computer vision and machine learning tools that employ artificial intelligence (AI), offer potential solutions with which to resolve this tradeoff. Here, we coupled a rigorous photogrammetric survey method with novel AI-assisted image segmentation software in order to quantify the impact of a coral bleaching event on a tropical reef, both at an ecologically meaningful spatial scale and with high spatial resolution. In addition to outlining our workflow, we highlight three key results: (1) dramatic changes in the three-dimensional surface areas of live and dead coral, as well as the ratio of live to dead colonies before and after bleaching; (2) a size-dependent pattern of mortality in bleached corals, where the largest corals were disproportionately affected, and (3) a significantly greater decline in the surface area of live coral, as revealed by our approximation of the 3D shape compared to the more standard planar area (2D) approach. The technique of photogrammetry allows us to turn 2D images into approximate 3D models in a flexible and efficient way. Increasing the resolution, accuracy, spatial extent, and efficiency with which we can quantify effects of disturbances will improve our ability to understand the ecological consequences that cascade from small to large scales, as well as allow more informed decisions to be made regarding the mitigation of undesired impacts

Eradication of chronic myeloid leukemia stem cells: a novel mathematical model predicts no therapeutic benefit of adding G-CSF to imatinib

Imatinib mesylate induces complete cytogenetic responses in patients with chronic myeloid leukemia (CML), yet many patients have detectable BCR-ABL transcripts in peripheral blood even after prolonged therapy. Bone marrow studies have shown that this residual disease resides within the stem cell compartment. Quiescence of leukemic stem cells has been suggested as a mechanism conferring insensitivity to imatinib, and exposure to the Granulocyte-Colony Stimulating Factor (G-CSF), together with imatinib, has led to a significant reduction in leukemic stem cells in vitro. In this paper, we design a novel mathematical model of stem cell quiescence to investigate the treatment response to imatinib and G-CSF. We find that the addition of G-CSF to an imatinib treatment protocol leads to observable effects only if the majority of leukemic stem cells are quiescent; otherwise it does not modulate the leukemic cell burden. The latter scenario is in agreement with clinical findings in a pilot study administering imatinib continuously or intermittently, with or without G-CSF (GIMI trial). Furthermore, our model predicts that the addition of G-CSF leads to a higher risk of resistance since it increases the production of cycling leukemic stem cells. Although the pilot study did not include enough patients to draw any conclusion with statistical significance, there were more cases of progression in the experimental arms as compared to continuous imatinib. Our results suggest that the additional use of G-CSF may be detrimental to patients in the clinic

RELIGHT: A compact and accurate RTI representation for the web

Relightable images have been widely used as a valuable tool in Cultural Heritage (CH) artifacts, including coins, bas-reliefs, paintings, and epigraphs. Reflection Transformation Imaging (RTI), a commonly used type of relightable images, consists of a per-pixel function which encodes the reflection behavior, estimated from a set of digital photographs acquired from a fixed view. Web visualisation tools for RTI images currently require to transmit substantial quantities of data in order to achieve high fidelity renderings. We propose a web-friendly compact representation for RTI images based on a joint interpolation-compression scheme that combines a PCA-based data reduction with a Gaussian Radial Basis Function (RBF) interpolation exhibiting superior performance in terms of quality/size ratio. This approach can be adapted also to other data interpolation schemes, and it is not limited to Gaussian RBF. The rendering part is simple to implement and computationally efficient allowing real-time rendering on low-end devices