416 research outputs found

    OneLab: On-demand deployment of IoT over IPv6: Infrastructure as a service for IEEE INFOCOM community

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    International audienceThis demonstration will explain how an experimenter can easily deploy an end-to-end IoT and Cloud infrastructure using the OneLab federation of testbeds. It will highlight the importance of using IPv6 in this context

    OneLab Tutorial: A Single Portal to Heterogeneous Testbeds

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    International audienceLarge-scale experimentation in varying types of environments is difficult to achieve, and until recently, experimenters have had to either construct their own platforms or rely on simulation, emulation, or analysis to gain results. However, these methods largely do not provide adequate or verified results. There lacked a viable model for the federation of large-scale testbeds that reconciled the challenges posed by how to provide a single entry point to access heterogeneous and distributed resources, and how to federate these resources that are under the control of multiple authorities. Efforts such as the FIRE initiative in Europe and GENI in the United States have worked to develop such a model, and the OneLab experimental facility, which came online in 2014, realizes this model, making a set of world-class testbeds freely available to researchers through a unique credential for each user and a common set of tools. OneLab provides a large-scale facility for rapid and remote testing that produces exhaustive results, at no charge to the experimenter. We allow users to deploy innovative experiments across our federated platforms that include the embedded object testbeds of FIT IoT-Lab, the cognitive radio testbed of FIT CorteXlab, the wireless testbeds of NITOS-Lab, and the internet overlay testbeds of PlanetLab Europe (PLE), which together provide thousands of nodes for experimentation. The OneLab portal allows single-entry point access to these platforms, and provides users with unique credentials. This is made possible through the adoption of Slice-based Federation Architecture (SFA), an API for authentication and authorization that was conceptualized by the GENI initiative in the US, where each authority authenticates users and authorizes access to the resources; and MySlice, the portal technology that we have developed to federate heterogeneous resources

    Federation of Internet experimentation facilities: architecture and implementation

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    International audienceRealistic experimentation facilities are indispensable to accelerate the design of novel Future Internet systems. As many of these ground-breaking new applications and services cover multiple innovation areas, the need for these solutions to be tested on cross-domain facilities with both novel infrastructure technologies and newly emerging service platforms is rising. The Fed4FIRE project therefore aims at federatingotherwise isolated experimentation facilities in order to foster synergies between research communities. Currently the federation includes over 15 facilities from the Future Internet Research and Experiment (FIRE) initiative, covering wired, wireless and sensor networks, SDN and OpenFlow, cloud computing, smart city services,etc.This paper presents the architecture and implementation details of the federation, based on an extensive set of requirements coming from infrastructure owners, service providers and support communitie

    Long-term results and GvHD after prophylactic and preemptive donor lymphocyte infusion after allogeneic stem cell transplantation for acute leukemia

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    We report on 318 patients with acute leukemia, receiving donor lymphocyte infusion (DLI) in complete hematologic remission (CHR) after allogeneic stem cell transplantation (alloSCT). DLI were applied preemptively (preDLI) for minimal residual disease (MRD, n‚ÄČ=‚ÄČ23) or mixed chimerism (MC, n‚ÄČ=‚ÄČ169), or as prophylaxis in high-risk patients with complete chimerism and molecular remission (proDLI, n‚ÄČ=‚ÄČ126). Median interval from alloSCT to DLI1 was 176 days, median follow-up was 7.0 years. Five-year cumulative relapse incidence (CRI), non-relapse mortality (NRM), leukemia-free and overall survival (LFS/OS) of the entire cohort were 29.1%, 12.7%, 58.2%, and 64.3%. Cumulative incidences of acute graft-versus-host disease (aGvHD) grade II‚ÄďIV¬į/chronic GvHD were 11.9%/31%. Nineteen patients (6%) died from DLI-induced GvHD. Age ‚Č•60 years (p‚ÄČ=‚ÄČ0.046), advanced stage at transplantation (p‚ÄČ=‚ÄČ0.003), shorter interval from transplantation (p‚ÄČ=‚ÄČ0.018), and prior aGvHD ‚Č•II¬į (p‚ÄČ=‚ÄČ0.036) were risk factors for DLI-induced GvHD. GvHD did not influence CRI, but was associated with NRM and lower LFS/OS. Efficacy of preDLI was demonstrated by decreasing MRD/increasing blood counts in 71%, and increasing chimerism in 70%. Five-year OS after preDLI for MRD/MC was 51%/68% among responders, and 37% among non-responders. The study describes response and outcome of DLI in CHR and helps to identify candidates without increased risk of severe GvHD

    Lenvatinib versus sorafenib in first-line treatment of patients with unresectable hepatocellular carcinoma: a randomised phase 3 non-inferiority trial

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    Background: In a phase 2 trial, lenvatinib, an inhibitor of VEGF receptors 1‚Äď3, FGF receptors 1‚Äď4, PDGF receptor őĪ, RET, and KIT, showed activity in hepatocellular carcinoma. We aimed to compare overall survival in patients treated with lenvatinib versus sorafenib as a first-line treatment for unresectable hepatocellular carcinoma. Methods: This was an open-label, phase 3, multicentre, non-inferiority trial that recruited patients with unresectable hepatocellular carcinoma, who had not received treatment for advanced disease, at 154 sites in 20 countries throughout the Asia-Pacific, European, and North American regions. Patients were randomly assigned (1:1) via an interactive voice‚Äďweb response system‚ÄĒwith region; macroscopic portal vein invasion, extrahepatic spread, or both; Eastern Cooperative Oncology Group performance status; and bodyweight as stratification factors‚ÄĒto receive oral lenvatinib (12 mg/day for bodyweight ‚Č•60 kg or 8 mg/day for bodyweight <60 kg) or sorafenib 400 mg twice-daily in 28-day cycles. The primary endpoint was overall survival, measured from the date of randomisation until the date of death from any cause. The efficacy analysis followed the intention-to-treat principle, and only patients who received treatment were included in the safety analysis. The non-inferiority margin was set at 1¬∑08. The trial is registered with ClinicalTrials.gov, number NCT01761266. Findings: Between March 1, 2013 and July 30, 2015, 1492 patients were recruited. 954 eligible patients were randomly assigned to lenvatinib (n=478) or sorafenib (n=476). Median survival time for lenvatinib of 13¬∑6 months (95% CI 12¬∑1‚Äď14¬∑9) was non-inferior to sorafenib (12¬∑3 months, 10¬∑4‚Äď13¬∑9; hazard ratio 0¬∑92, 95% CI 0¬∑79‚Äď1¬∑06), meeting criteria for non-inferiority. The most common any-grade adverse events were hypertension (201 [42%]), diarrhoea (184 [39%]), decreased appetite (162 [34%]), and decreased weight (147 [31%]) for lenvatinib, and palmar-plantar erythrodysaesthesia (249 [52%]), diarrhoea (220 [46%]), hypertension (144 [30%]), and decreased appetite (127 [27%]) for sorafenib. Interpretation: Lenvatinib was non-inferior to sorafenib in overall survival in untreated advanced hepatocellular carcinoma. The safety and tolerability profiles of lenvatinib were consistent with those previously observed

    The C5a/C5a receptor 1 axis controls tissue neovascularization through CXCL4 release from platelets

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    Platelets contribute to the regulation of tissue neovascularization, although the specific factors underlying this function are unknown. Here, we identified the complement anaphylatoxin C5a-mediated activation of C5a receptor 1 (C5aR1) on platelets as a negative regulatory mechanism of vessel formation. We showed that platelets expressing C5aR1 exert an inhibitory effect on endothelial cell functions such as migration and 2D and 3D tube formation. Growth factor- and hypoxia-driven vascularization was markedly increased in C5ar1(‚ąí/‚ąí) mice. Platelet-specific deletion of C5aR1 resulted in a proangiogenic phenotype with increased collateralization, capillarization and improved pericyte coverage. Mechanistically, we found that C5a induced preferential release of CXC chemokine ligand 4 (CXCL4, PF4) from platelets as an important antiangiogenic paracrine effector molecule. Interfering with the C5aR1-CXCL4 axis reversed the antiangiogenic effect of platelets both in vitro and in vivo. In conclusion, we identified a mechanism for the control of tissue neovascularization through C5a/C5aR1 axis activation in platelets and subsequent induction of the antiangiogenic factor CXCL4

    Increasing Use of Allogeneic Hematopoietic Cell Transplantation in Patients Aged 70 Years and Older in the United States

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    In this study, we evaluated trends and outcomes of allogeneic hematopoietic cell transplantation (HCT) in adults ‚Č• 70 years with hematologic malignancies across the United States. Adults ‚Č• 70 years with a hematologic malignancy undergoing first allogeneic HCT in the United States between 2000 and 2013 and reported to the Center for International Blood and Marrow Transplant Research were eligible. Transplant utilization and transplant outcomes, including overall survival (OS), progression-free survival (PFS), and transplant-related mortality (TRM) were studied. One thousand one hundred and six patients ‚Č• 70 years underwent HCT across 103 transplant centers. The number and proportion of allografts performed in this population rose markedly over the past decade, accounting for 0.1% of transplants in 2000 to 3.85% (N = 298) in 2013. Acute myeloid leukemia and myelodysplastic syndromes represented the most common disease indications. Two-year OS and PFS significantly improved over time (OS: 26% [95% confidence interval (CI), 21% to 33%] in 2000-2007 to 39% [95% CI, 35% to 42%] in 2008-2013, P \u3c .001; PFS: 22% [16% to 28%] in 2000-2007 to 32% [95% CI, 29% to 36%] in 2008-2013, P = .003). Two-year TRM ranged from 33% to 35% and was unchanged over time (P = .54). Multivariable analysis of OS in the modern era of 2008-2013 revealed higher comorbidity by HCT comorbidity index ‚Č• 3 (hazard ratio [HR], 1.27; P = .006), umbilical cord blood graft (HR, 1.97; P = .0002), and myeloablative conditioning (HR, 1.61; P = .0002) as adverse factors. Over the past decade, utilization and survival after allogeneic transplant have increased in patients ‚Č• 70 years. Select adults ‚Č•70 years with hematologic malignancies should be considered for transplant

    Clinical practice recommendation on hematopoietic stem cell transplantation for acute myeloid leukemia patients with FLT3 internal tandem duplication: a position statement from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation

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    The FMS-like tyrosine kinase 3 (FLT3) gene is mutated in 25-30% of patients with acute myeloid leukemia . Because of the poor prognosis associated with FMS-like tyrosine kinase 3 internal tandem duplication mutated Acute myeloid leukemia, allogeneic-hematopoietic stem-cell transplantation was commonly performed in first complete remission. Remarkable progress has been made in frontline treatments with the incorporation of FLT3 inhibitors and the development of highly sensitive minimal/measurable residual disease assays. Similarly, recent progress in allogeneic-hematopoietic stem-cell transplantation includes improvement of transplant techniques, the use of haplo-identical donors in patients lacking an HLA matched donor, and the introduction of FLT3 inhibitors as posttransplant maintenance therapy. Nevertheless, current transplant strategies vary between centers and differ in terms of transplant indications based on the internal tandem duplication allelic ratio and concomitant nucleophosmin-1 mutation, as well as in terms of post-transplant maintenance/consolidation. This review generated by international leukemia or transplant experts, mostly from the European Society for Blood and Marrow Transplantation, attempts to develop a position statement on best approaches for allogeneic-hematopoietic stem-cell transplantation for acute myeloid leukemia with FMS-like tyrosine kinase internal tandem duplication including indications and modalities of allogeneic-hematopoietic stem-cell transplantation and on potential optimization of post-transplant maintenance with FMS-like tyrosine kinase inhibitors

    Prophylactic, preemptive, and curative treatment for sinusoidal obstruction syndrome/veno-occlusive disease in adult patients : a position statement from an international expert group

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    Sinusoidal obstruction syndrome, also known as veno-occlusive disease (SOS/VOD), is a potentially life-threatening complication that can develop after hematopoietic cell transplantation (HCT). While SOS/VOD may resolve within a few weeks in the majority of patients with mild-to-moderate disease, the most severe forms result in multiorgan dysfunction and are associated with a high mortality rate (>80%). Therefore, careful surveillance may allow early detection of SOS/VOD, particularly as the licensed available drug is proven to be effective and reduce mortality. The aim of this work is to propose an international consensus guideline for the treatment and prevention of SOS/VOD in adult patients, on behalf of an international expert group.Peer reviewe
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