HF Radar activity in European coastal seas: next steps toward a Pan-European HF Radar network

High Frequency Radar (HFR) is a land-based remote sensing instrument offering a unique insight to coastal ocean variability, by providing synoptic, high frequency and high resolution data at the ocean atmosphere interface. HFRs have become invaluable tools in the field of operational oceanography for measuring surface currents, waves and winds, with direct applications in different sectors and an unprecedented potential for the integrated management of the coastal zone. In Europe, the number of HFR networks has been showing a significant growth over the past 10 years, with over 50 HFRs currently deployed and a number in the planning stage. There is also a growing literature concerning the use of this technology in research and operational oceanography. A big effort is made in Europe toward a coordinated development of coastal HFR technology and its products within the framework of different European and international initiatives. One recent initiative has been to make an up-to-date inventory of the existing HFR operational systems in Europe, describing the characteristics of the systems, their operational products and applications. This paper offers a comprehensive review on the present status of European HFR network, and discusses the next steps toward the integration of HFR platforms as operational components of the European Ocean Observing System, designed to align and integrate Europe's ocean observing capacity for a truly integrated end-to-end observing system for the European coasts

Relative bioequivalence of amoxicillin dissolved in breast milk

BACKGROUND: Oral antibiotics use in infants in developing countries is challenging because liquid formulations are often unavailable. However, dissolving solid formulation of drugs in water poses a risk of gastrointestinal infection. Although mother's milk may be a potential vehicle, no evidence exists to indicate that antibiotics dissolved in human milk are bioequivalent to those dissolved in water. Therefore, we compared pharmacokinetic parameters of an orally administered antibiotic, amoxicillin, dissolved in human milk, to those of water-dissolved amoxicillin. METHODS: A pharmacokinetic study was conducted in 16 healthy adult volunteers in a randomised crossover design. Marketed amoxicillin powder for suspension was dissolved in either human milk or water at a final concentration of 50 mg/mL, and 10 mL was given orally in a fasting state. Timed blood samples were obtained and plasma amoxicillin was quantified using liquid chromatography-mass spectrometry. FINDINGS: Results showed that pharmacokinetic parameters, including area-under-the-curve, Cmax and half-life of the water-based and milk-based amoxicillin administration were not significantly different. 90% CIs of the ratios of these parameters in concomitant breast milk administration to those of water were within 89% and 116%, suggesting they are bioequivalent (defined as a range between 80% and 125%). INTERPRETATION: We conclude that oral administration of amoxicillin dissolved in human milk at 50 mg/mL results in pharmacokinetics profiles comparable to amoxicillin dissolved in water. Pharmaceutical interactions between amoxicillin and breast milk are unlikely, suggesting no need to modify dosing schedules.Fil: Yazdani Brojeni, Parvaneh. University Of Toronto. Hospital For Sick Children; CanadáFil: García Bournissen, Facundo. University Of Toronto. Hospital For Sick Children; Canadá. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Fujii, Hisaki. University Of Toronto. Hospital For Sick Children; CanadáFil: Tanoshima, Reo. University Of Toronto. Hospital For Sick Children; CanadáFil: Ito, Shinya. University Of Toronto. Hospital For Sick Children; Canad

Humanized Chronic Graft-versus-Host Disease in NOD-SCID il2rγ-/- (NSG) Mice with G-CSF-Mobilized Peripheral Blood Mononuclear Cells following Cyclophosphamide and Total Body Irradiation

<div><p>Chronic graft-versus-host disease (cGvHD) is the major source of late phase morbidity and mortality after allogeneic hematopoietic stem cell transplantation. Humanized acute GvHD (aGvHD) <i>in vivo</i> models using NOD-SCID il2rγ-/- (NSG) mice are well described and are important tools for investigating pathogenicity of human cells <i>in vivo</i>. However, there have been only few reported humanized cGvHD mouse models. We evaluated if prolonged inflammation driven by low dose G-CSF-mobilized human PBMCs (G-hPBMCs) would lead to cGvHD following cyclophosphamide (CTX) administration and total body irradiation (TBI) in NSG mice. Engraftment was assessed in peripheral blood (PB) and in specific target organs by either flow cytometry or immunohistochemistry (IHC). Tissue samples were harvested 56 days post transplantation and were evaluated by a pathologist. Some mice were kept for up to 84 days to evaluate the degree of fibrosis. Mice that received CTX at 20mg/kg did not show aGvHD with stable expansion of human CD45⁺ CD3⁺ T-cells in PB (mean; 5.8 to 23.2%). The pathology and fibrosis scores in the lung and the liver were significantly increased with aggregation of T-cells and hCD68⁺ macrophages. There was a correlation between liver pathology score and the percentage of hCD68⁺ cells, suggesting the role of macrophage in fibrogenesis in NSG mice. In order to study long-term survival, 6/9 mice who survived more than 56 days showed increased fibrosis in the lung and liver at the endpoint, which suggests the infiltrating hCD68⁺ macrophages may be pathogenic. It was shown that the combination of CTX and TBI with a low number of G-hPBMCs (1x10⁶) leads to chronic lung and liver inflammation driven by a high infiltration of human macrophage and mature human T cells from the graft, resulting in fibrosis of lung and liver in NSG mice. In conclusion this model may serve as an important pre-clinical model to further current understanding of the roles of human macrophages in cGvHD.</p></div

Engraftment of human hematopoietic cells in NSG mice.

<p>Peripheral blood chimerism analysis (% of hCD45⁺ cells) was performed by flow cytometry 56 days post transplantation. (A; n = 8 donor 1, n = 12 donor 2). In donor 2, % of hCD3/hCD45⁺ cells was compared on day 28 and day 56 (B; n = 12 mice each). Lung (C) or liver (D) from NSG mice were examined for human CD4, CD8, CD20 and CD68 engraftment by IHC 56 days post transplantation. Three randomly selected sections per slide from at least 3 mice each were placed on the optical photomicroscope and observed under the X20 objective. Data were calculated as: % positive cells = positive nuclei cells ⁄ total cells nuclei x 100. All results are presented as mean ± SEM.</p

Association between liver pathology and the engraftment level in mice with G-hPBMCs.

<p>Liver pathology score from mice with donor 1 (left; n = 8) was compared with donor 2 (right; more than 18% hCD45⁺ cells in PB (n = 6), center; less than 18% in PB (n = 3))(A). Correlation between liver pathology score and % hCD68⁺ cells in liver was analyzed by linear regression (donor 1 and 2; n = 10) (B).</p

Effect of cyclophosphamide in NSG mice 56 days post transplantation.

<p>NSG mice received 20mg/kg or 60mg/kg cyclophosphamide by intraperitoneal injection (day -3, -2) and 200cGy X-ray (day-1) followed by i.v. injection of 1x10⁶ G-hPBMCs or 1x10⁵ CD34⁺ cells on day 0. Survival (A) and weight loss (B) were monitored until 56 days post transplantation. Each experiment was done in triplicate and every group consisted of at least 7 mice.</p