Developing a global operational seasonal hydro-meteorological forecasting system: GloFAS-Seasonal v1.0

Global overviews of upcoming flood and drought events are key for many applications, including disaster risk reduction initiatives. Seasonal forecasts are designed to provide early indications of such events weeks, or even months, in advance, but seasonal forecasts for hydrological variables at large or global scales are few and far between. Here, we present the first operational global scale seasonal hydro-meteorological forecasting system: GloFAS-Seasonal. Developed as an extension of the Global Flood Awareness System (GloFAS), GloFAS-Seasonal couples seasonal meteorological forecasts from ECMWF with a hydrological model, to provide openly available probabilistic forecasts of river flow out to 4 months ahead for the global river network. This system has potential benefits not only for disaster risk reduction through early awareness of floods and droughts, but also for water-related sectors such as agriculture and water resources management, in particular for regions where no other forecasting system exists. We describe the key hydro-meteorological components and computational framework of GloFAS-Seasonal, alongside the forecast products available, before discussing initial evaluation results and next steps

Measurement of secondary particle production induced by particle therapy ion beams impinging on a PMMA target

Particle therapy is a technique that uses accelerated charged ions for cancer treatment and combines a high irradiation precision with a high biological effectiveness in killing tumor cells [1]. Informations about the secondary particles emitted in the interaction of an ion beam with the patient during a treatment can be of great interest in order to monitor the dose deposition. For this purpose an experiment at the HIT (Heidelberg Ion-Beam Therapy Center) beam facility has been performed in order to measure fluxes and emission profiles of secondary particles produced in the interaction of therapeutic beams with a PMMA target. In this contribution some preliminary results about the emission profiles and the energy spectra of the detected secondaries will be presente

Underground operation of the ICARUS T600 LAr-TPC: first results

Open questions are still present in fundamental Physics and Cosmology, like the nature of Dark Matter, the matter-antimatter asymmetry and the validity of the particle interaction Standard Model. Addressing these questions requires a new generation of massive particle detectors exploring the subatomic and astrophysical worlds. ICARUS T600 is the first large mass (760 ton) example of a novel detector generation able to combine the imaging capabilities of the old famous "bubble chamber" with an excellent energy measurement in huge electronic detectors. ICARUS T600 now operates at the Gran Sasso underground laboratory, studying cosmic rays, neutrino oscillation and proton decay. Physical potentialities of this novel telescope are presented through few examples of neutrino interactions reconstructed with unprecedented details. Detector design and early operation are also reported.Comment: 14 pages, 8 figures, 2 tables. Submitted to Jins

Maternal smoking during pregnancy and scholastic achievement in childhood: evidence from the LIFECOURSE cohort study.

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked FilesResearch on the impact of maternal smoking during pregnancy (MSDP) on scholastic achievement in the offspring has shown conflicting findings. The objective of this study was to assess the impact of MSDP on scholastic achievement in a birth cohort of children in 4th, 7th and 10th grades.We analysed data from the LIFECOURSE study, a cohort study of risk and protective factors in all children born in Reykjavik, Iceland, in the year 2000 (N = 1151, girls = 49.3%). Retrospective registry data for 2014-2015 were merged with prospective survey data that were collected in April 2016. Data on MSDP were assessed during regular antenatal visits at the end of the first trimester. Standardized academic achievement scores were obtained from official school transcripts. Data were analysed using OLS regressions that were entered in three hierarchical blocks.Children of mothers who smoked tobacco during the first trimester consistently revealed between 5% and 7% lower scores on standardized academic achievement in 4th, 7th and 10th grade (∼6-8 points on a normally distributed 120 point scale) than those of mothers who had not smoked tobacco during this period (P < 0.05). These findings held after controlling for several factors associated with the time of birth (e.g. birth weight, maternal age at birth, birth order, parental cohabitation and household income), as well as the year of scholastic assessment (parental cohabitation, household income and parental education).Maternal smoking during pregnancy was negatively related to scholastic achievement in the offspring during 4th, 7th and 10th grade.European Research Counci

Cell proliferation within small intestinal crypts is the principal driving force for cell migration on villi

The functional integrity of the intestinal epithelial barrier relies on tight coordination of cell proliferation and migration, with failure to regulate these processes resulting in disease. It is not known whether cell proliferation is sufficient to drive epithelial cell migration during homoeostatic turnover of the epithelium. Nor is it known precisely how villus cell migration is affected when proliferation is perturbed. Some reports suggest that proliferation and migration may not be related while other studies support a direct relationship. We used established cell-tracking methods based on thymine analog cell labeling and developed tailored mathematical models to quantify cell proliferation and migration under normal conditions and when proliferation is reduced and when it is temporarily halted. We found that epithelial cell migration velocities along the villi are coupled to cell proliferation rates within the crypts in all conditions. Furthermore, halting and resuming proliferation results in the synchronized response of cell migration on the villi. We conclude that cell proliferation within the crypt is the primary force that drives cell migration along the villus. This methodology can be applied to interrogate intestinal epithelial dynamics and characterize situations in which processes involved in cell turnover become uncoupled, including pharmacological treatments and disease models

Non-myeloablative autologous haematopoietic stem cell transplantation expands regulatory cells and depletes IL-17 producing mucosal-associated invariant T cells in multiple sclerosis

Autologous haematopoietic stem cell transplantation has been tried as one experimental strategy for the treatment of patients with aggressive multiple sclerosis refractory to other immunotherapies. The procedure is aimed at ablating and repopulating the immune repertoire by sequentially mobilizing and harvesting haematopoietic stem cells, administering an immunosuppressive conditioning regimen, and re-infusing the autologous haematopoietic cell product. ‘Non-myeloablative' conditioning regimens to achieve lymphocytic ablation without marrow suppression have been proposed to improve safety and tolerability. One trial with non-myeloablative autologous haematopoietic stem cell transplantation reported clinical improvement and inflammatory stabilization in treated patients with highly active multiple sclerosis. The aim of the present study was to understand the changes in the reconstituted immune repertoire bearing potential relevance to its mode of action. Peripheral blood was obtained from 12 patients with multiple sclerosis participating in the aforementioned trial and longitudinally followed for 2 years. We examined the phenotype and function of peripheral blood lymphocytes by cell surface or intracellular staining and multi-colour fluorescence activated cell sorting alone or in combination with proliferation assays. During immune reconstitution post-transplantation we observed significant though transient increases in the proportion of CD4+FoxP3+ T cells and CD56high natural killer cell subsets, which are cell subsets associated with immunoregulatory function. CD8+CD57+ cytotoxic T cells were persistently increased after therapy and were able to suppress CD4+ T cell proliferation with variable potency. In contrast, a CD161high proinflammatory CD8+ T cell subset was depleted at all time-points post-transplantation. Phenotypic characterization revealed that the CD161highCD8+ T cells were mucosal-associated invariant T cells, a novel cell population originating in the gut mucosa but expressing the central nervous system-homing receptor CCR6. Detection of mucosal-associated invariant T cells in post-mortem multiple sclerosis brain white matter active lesions confirmed their involvement in the disease pathology. Intracellular cytokine staining demonstrated interferon γ and interleukin 17 production and lack of interleukin 10 production, a pro-inflammatory profile. Mucosal-associated invariant T cell frequency did not change in patients treated with interferon β; and was more depleted after autologous haematopoietic stem cell transplantation than in patients who had received high-dose cyclophosphamide (n = 7) or alemtuzumab (n = 21) treatment alone, suggesting an additive or synergistic effect of the conditioning regime components. We propose that a favourably modified balance of regulatory and pro-inflammatory lymphocytes underlies the suppression of central nervous system inflammation in patients with multiple sclerosis following non-myeloablative autologous haematopoietic stem cell transplantation with a conditioning regimen consisting of cyclophosphamide and alemtuzuma

Fibrous Organic Soils: Linking Multiscale Experimental and Numerical Approaches

Differently from any other soil, natural fibrous organic soils show high compressibility and considerable creep combined with extremely high friction angle. These unusual characteristics are attributed to the role of the natural heterogeneous system of fibres, which is assumed to hinder reliable description of the mechanical behaviour of these soils. To fill the knowledge gap, diverse experimental and numerical tools are being developed, in an attempt to isolate and model the kinematics of fibres at the micro-scale. Combining these approaches and upscaling the information at the continuum level allows addressing more efficiently and more robustly the analysis of the engineering response of these soils, and provides a tool for better evaluating the possible consequences of accelerated degradation of the fibrous fabric at increasing climatic stresses

Space Applications of the FLUKA Monte-Carlo Code: Lunar and Planetary Exploration

NASA has recognized the need for making additional heavy-ion collision measurements at the U.S. Brookhaven National Laboratory in order to support further improvement of several particle physics transport-code models for space exploration applications. FLUKA has been identified as one of these codes and we will review the nature and status of this investigation as it relates to high-energy heavy-ion physics

Allergen immunotherapy for IgE-mediated food allergy : a systematic review and meta-analysis

Background: The European Academy of Allergy and Clinical Immunology (EAACI) is developing Guidelines for Allergen Immunotherapy (AIT) for IgE-mediated Food Allergy. To inform the development of clinical recommendations, we sought to critically assess evidence on the effectiveness, safety and cost-effectiveness of AIT in the management of food allergy. Methods: We undertook a systematic review and meta-analysis that involved searching nine international electronic databases for randomized controlled trials (RCTs) and nonrandomized studies (NRS). Eligible studies were independently assessed by two reviewers against predefined eligibility criteria. The quality of studies was assessed using the Cochrane Risk of Bias tool for RCTs and the Cochrane ACROBAT-NRS tool for quasi-RCTs. Random-effects meta-analyses were undertaken, with planned subgroup and sensitivity analyses. Results: We identified 1814 potentially relevant papers from which we selected 31 eligible studies, comprising of 25 RCTs and six NRS, studying a total of 1259 patients. Twenty-five trials evaluated oral immunotherapy (OIT), five studies investigated sublingual immunotherapy, and one study evaluated epicutaneous immunotherapy. The majority of these studies were in children. Twenty-seven studies assessed desensitization, and eight studies investigated sustained unresponsiveness postdiscontinuation of AIT. Meta-analyses demonstrated a substantial benefit in terms of desensitization (risk ratio (RR) = 0.16, 95% CI 0.10, 0.26) and suggested, but did not confirm sustained unresponsiveness (RR = 0.29, 95% CI 0.08, 1.13). Only one study reported on disease-specific quality of life (QoL), which reported no comparative results between OIT and control group. Meta-analyses revealed that the risk of experiencing a systemic adverse reaction was higher in those receiving AIT, with a more marked increase in the risk of local adverse reactions. Sensitivity analysis excluding those studies judged to be at high risk of bias demonstrated the robustness of summary estimates of effectiveness and safety of AIT for food allergy. None of the studies reported data on health economic analyses. Conclusions: AIT may be effective in raising the threshold of reactivity to a range of foods in children with IgE-mediated food allergy whilst receiving (i.e. desensitization) and post-discontinuation of AIT. It is, however, associated with a modest increased risk in serious systemic adverse reactions and a substantial increase in minor local adverse reactions. More data are needed in relation to adults, long term effects, the impact on QoL and the cost-effectiveness of AIT.Peer reviewe

Measurement of Through-Going Particle Momentum By Means Of Multiple Scattering With The ICARUS T600 TPC

The ICARUS collaboration has demonstrated, following the operation of a 600 ton (T600) detector at shallow depth, that the technique based on liquid Argon TPCs is now mature. The study of rare events, not contemplated in the Standard Model, can greatly benefit from the use of this kind of detectors. In particular, a deeper understanding of atmospheric neutrino properties will be obtained thanks to the unprecedented quality of the data ICARUS provides. However if we concentrate on the T600 performance, most of the $\nu_\mu$ charged current sample will be partially contained, due to the reduced dimensions of the detector. In this article, we address the problem of how well we can determine the kinematics of events having partially contained tracks. The analysis of a large sample of atmospheric muons collected during the T600 test run demonstrate that, in case the recorded track is at least one meter long, the muon momentum can be reconstructed by an algorithm that measures the Multiple Coulomb Scattering along the particle's path. Moreover, we show that momentum resolution can be improved by a factor two using an algorithm based on the Kalman Filtering technique