ICONA: Inter Cluster ONOS Network Application

Several Network Operating Systems (NOS) have been proposed in the last few years for Software Defined Networks; however, a few of them are currently offering the resiliency, scalability and high availability required for production environments. Open Networking Operating System (ONOS) is an open source NOS, designed to be reliable and to scale up to thousands of managed devices. It supports multiple concurrent instances (a cluster of controllers) with distributed data stores. A tight requirement of ONOS is that all instances must be close enough to have negligible communication delays, which means they are typically installed within a single datacenter or a LAN network. However in certain wide area network scenarios, this constraint may limit the speed of responsiveness of the controller toward network events like failures or congested links, an important requirement from the point of view of a Service Provider. This paper presents ICONA, a tool developed on top of ONOS and designed in order to extend ONOS capability in network scenarios where there are stringent requirements in term of control plane responsiveness. In particular the paper describes the architecture behind ICONA and provides some initial evaluation obtained on a preliminary version of the tool.Comment: Paper submitted to a conferenc

Fluocinolone acetonide vitreous insert for chronic diabetic macular oedema: a systematic review with meta-analysis of real-world experience

We conducted a meta-analysis of real-world studies on the 0.19 mg Fluocinolone Acetonide (FAc) intravitreal implant for chronic diabetic macular oedema (DMO), comparing these findings with the Fluocinolone Acetonide for Diabetic Macular Edema (FAME) study. The primary outcome was mean change of best corrected visual acuity (BCVA) at 24 months. Secondary outcomes were 36-month mean BCVA, mean central macular thickness (CMT) change, rates of eyes receiving supplementary intravitreal therapy, cataract surgery, intraocular pressure (IOP)-lowering drops and glaucoma surgery. Mean differences (MDs) with 95% confidence intervals (CIs) were calculated. Nine real-world studies were included. The FAc implant yielded a significantly improved BCVA at 24 and 36 months (24-month MD = 4.52; 95% CI 2.56–6.48; 36-month MD = 8.10; 95% CI 6.34–9.86). These findings were comparable with the FAME study. The FAc implant yielded significantly reduced 24- and 36-month CMT. Pooled proportions of cataract surgery, IOP-lowering drops and glaucoma surgery were 39%, 27% and 3%, respectively, all lower than the FAME study. Pooled estimate of supplementary intravitreal therapy was 39%, higher than the 15.2% of the FAME study. This meta-analysis of real-world studies confirms favorable visual and anatomical outcomes following FAc insert for chronic DMO. In real-life studies more than one third of patients received supplementary intravitreal therapy, an issue that needs to be further explored

Intravitreal Dexamethasone Implant for Postoperative Macular Oedema Secondary to Vitrectomy for Epiretinal Membrane and Retinal Detachment: A Systematic Review and Meta-Analysis

Purpose. To evaluate the efficacy of intravitreal dexamethasone implant (DEX) for the treatment of macular oedema secondary to vitrectomy for epiretinal membrane (ERM) and retinal detachment (RD) by conducting a systematic review with meta-analysis of published studies. Methods. Studies reporting clinical outcomes of DEX use for the treatment of macular oedema secondary to ERM and RD vitrectomy were searched on PubMed and Embase databases. The primary outcome was best-corrected visual acuity (BCVA) change between baseline and post-DEX treatment, reported as mean difference (MD) with 95% confidence interval (CI). Mean central macular thickness (CMT) change was assessed as a secondary outcome. Postimplant adverse events, including intraocular pressure rise and cataract development, were reported as well. Results. Five uncontrolled studies, 1 nonrandomized controlled study, and 1 randomized controlled study were included, with a total of 5 cohorts and 3 cohorts in the ERM group and RD group, respectively. Considering the last available follow-up, a significant improvement in postimplant BCVA was found in the overall population, irrespective of the indication for vitrectomy (MD = -0.28, 95% CI = -0.37, -0.20; p<0.001), but with significant heterogeneity. In either group, mean BCVA significantly improved following the implant (in the ERM group, MD = -0.31, 95% CI = -0.40, -0.22; in the RD group, MD = -0.22, 95% CI = -0.41, -0.03), with no difference between the two groups (p=0.41). However, there was significant heterogeneity in both groups. Considering the last available follow-up, a significant CMT reduction was found in the overall population, irrespective of the indication for vitrectomy (MD = -129.75, 95% CI = -157.49, -102.01; p<0.001). In the ERM group, a significant CMT reduction was shown following DEX (MD = -133.41, 95% CI = -155.37, -111.45; p<0.001), with no heterogeneity. In the RD group, mean CMT reduction was borderline significant (MD = -128.37, 95% CI = -253.57, -3.18; p=0.040), with significant heterogeneity. No difference in CMT improvement was found between the two groups (p=0.94). Conclusion. This meta-analysis showed that DEX yielded a significant improvement in visual and anatomical outcomes, even if limited by significant heterogeneity. Dexamethasone implant represents an effective treatment for postoperative macular oedema secondary to ERM and RD vitrectomy

Epiretinal Membrane Vitrectomy With and Without Intraoperative Intravitreal Dexamethasone Implant: A Systematic Review With Meta-Analysis

Purpose: To evaluate the efficacy of vitrectomy combined with intravitreal dexamethasone implant vs. vitrectomy without the implant in patients with epiretinal membrane (ERM) by conducting a systematic review and meta-analysis. Methods: Studies that compared ERM vitrectomy with and without intraoperative dexamethasone implant with a follow-up 653 months were included. The primary outcome was mean best corrected visual acuity (BCVA) change between eyes undergoing ERM vitrectomy combined with dexamethasone implant (DEX group) and eyes undergoing ERM vitrectomy alone (control group) at 3 months. Secondary outcomes included mean BCVA change at 6 months and mean optical coherence tomography central macular thickness (CMT) change at both 3-months and 6-months follow-up. Mean differences (MDs) with their 95% confidence interval (95%CI) were calculated. Meta-analyses were based either on random effect model or fixed effect model according to heterogeneity. Results: Four studies were included. At 3 months, ERM vitrectomy combined with dexamethasone implant yielded a greater visual gain compared to vitrectomy alone (MD = 9.7; 95%CI = 2.6\u201316.8; p = 0.01). However, significant heterogeneity was found. A sensitivity analysis excluding the only retrospective non-randomized study confirmed a greater visual gain in the DEX group (MD = 7.1; 95%CI = 2.7\u201311.6; p < 0.01), with no heterogeneity. At 6 months, a non-significant but borderline difference in visual gain was shown between in the two groups (MD = 5.1; 95%CI = 120.3\u201310.5; p = 0.06), with no heterogeneity. Three-month analysis of CMT revealed a greater reduction in the DEX group (MD = 1280.2; 95%CI = 12149.1\u201311.2; p = 0.02), but with significant heterogeneity. A sensitivity analysis excluding the only retrospective non-randomized study allowed to reduce heterogeneity, but no difference in 3-months CMT change was found between the two groups (MD = 1250.0; 95%CI = 12106.2\u20136.2; p = 0.08). At 6 months, no difference in CMT change was shown between the two groups (MD = 1248.5; 95%CI = 12120.5\u201323.5; p = 0.19), with significant heterogeneity. Conclusions: Intraoperative dexamethasone implant in eyes undergoing vitrectomy for ERM provided a better visual outcome at 3 months compared to ERM vitrectomy without the implant, with limited evidence of better anatomic outcome as well. Further studies are needed to ascertain whether dexamethasone implant would ensure a significant long-term visual benefit as a result of a faster reduction of macular thickening

Primary vitrectomy for degenerative and tractional lamellar macular holes: A systematic review and meta-analysis

Purpose To assess the efficacy of vitrectomy in degenerative and tractional lamellar macular holes (LMHs) by meta-analysis of published studies. Methods PubMed, Medline and Embase databases were searched up to May 2020. Included cohorts were divided into three groups: degenerative LMH group, lamellar hole associated epiretinal proliferation (LHEP) group and tractional LMH group. LHEP is likely to be associated with degenerative LMHs, but less commonly could be associated with mixed LMHs. To reduce risk of possible misclassification bias, eyes with LHEP which could not have been precisely classified by the authors, were included into the LHEP group. The primary outcome was to investigate the visual change following primary vitrectomy in the degenerative LMH and LHEP group versus the tractional LMH group. A sensitivity analysis excluding the LHEP group was also performed on the primary outcome. Mean difference (MD) in best corrected visual acuity between baseline and post-treatment was calculated, along with 95% confidence interval (CI). Rate of incidence of post-operative full-thickness macular hole (FTMH) was assessed as secondary outcome. Results Thirteen studies were included. Pooled analyses including all groups showed a significant visual improvement following vitrectomy (pre-post MD = -0.17;95%CI = -0.22,-0.12; p<0.001), with no difference in visual improvement between the degenerative LMH and LHEP group and the tractional LMH group. The sensitivity analysis excluding LHEP group confirmed no difference in visual change between the degenerative LMH group (pre-post MD = -0.18;95%CI = -0.24,-0.12;p<0.001) and the tractional LMH group (MD = -0.16;95%CI = -0.26,-0.07;p<0.001). The incidence rate of post-operative FTMH was higher in the degenerative LMH and LHEP group than in the tractional LMH group (p = 0.002). Conclusion Primary vitrectomy for LMH ensured a favorable visual outcome, with no difference in visual gain between degenerative and tractional LMHs. However, a higher incidence of post-operative FTMHs was found in eyes with the degenerative LMH subtype

Lipocalin-2 Deficiency Attenuates Insulin Resistance Associated With Aging and Obesity

OBJECTIVE - The proinflammatory cytokines/adipokines produced from adipose tissue act in an autocrine and/or endocrine manner to perpetuate local inflammation and to induce peripheral insulin resistance. The present study investigates whether lipocalin-2 deficiency or replenishment with this adipokine has any impact on systemic insulin sensitivity and the underlying mechanisms. METHODS AND RESULTS - Under conditions of aging or dietary-/genetic-induced obesity, lipocalin-2 knockout (Lcn2-KO) mice show significantly decreased fasting glucose and insulin levels and improved insulin sensitivity compared with their wild-type littermates. Despite enlarged fat mass, inflammation and the accumulation of lipid peroxidation products are significantly attenuated in the adipose tissues of Lcn2-KO mice. Adipose fatty acid composition of these mice varies significantly from that in wild-type animals. The amounts of arachidonic acid (C20:4 n6) are elevated by aging and obesity and are paradoxically further increased in adipose tissue, but not skeletal muscle and liver of Lcn2-KO mice. On the other hand, the expression and activity of 12-lipoxygenase, an enzyme responsible for metabolizing arachidonic acid, and the production of tumor necrosis factor-α (TNF-α), a critical insulin resistance-inducing factor, are largely inhibited by lipocalin-2 deficiency. Lipocalin-2 stimulates the expression and activity of 12-lipoxygenase and TNF-α production in fat tissues. Cinnamyl-3,4- dihydroxy-α-cyanocinnamate (CDC), an arachidonate lipoxygenase inhibitor, prevents TNF-α expression induced by lipocalin-2. Moreover, treatment with TNF-α neutralization antibody or CDC significantly attenuated the differences of insulin sensitivity between wild-type and Lcn2-KO mice. CONCLUSIONS - Lipocalin-2 deficiency protects mice from developing aging- and obesity-induced insulin resistance largely by modulating 12-lipoxygenase and TNF-α levels in adipose tissue. © 2010 by the American Diabetes Association.link_to_OA_fulltex

DTT - Divertor Tokamak Test facility: A testbed for DEMO

The effective treatment of the heat and power exhaust is a critical issue in the road map to the realization of the fusion energy. In order to provide possible, reliable, well assessed and on-time answers to DEMO, the Divertor Tokamak Test facility (DTT) has been conceived and projected to be carried out and operated within the European strategy in fusion technology. This paper, based on the invited plenary talk at the 31st virtual SOFT Conference 2020, provides an overview of the DTT scientific proposal, which is deeply illustrated in the 2019 DTT Interim Design Report

Divertor of the European DEMO: Engineering and technologies for power exhaust

In a power plant scale fusion reactor, a huge amount of thermal power produced by the fusion reaction and external heating must be exhausted through the narrow area of the divertor targets. The targets must withstand the intense bombardment of the diverted particles where high heat fluxes are generated and erosion takes place on the surface. A considerable amount of volumetric nuclear heating power must also be exhausted. To cope with such an unprecedented power exhaust challenge, a highly efficient cooling capacity is required. Furthermore, the divertor must fulfill other critical functions such as nuclear shielding and channeling (and compression) of exhaust gas for pumping. Assuring the structural integrity of the neutron-irradiated (thus embrittled) components is a crucial prerequisite for a reliable operation over the lifetime. Safety, maintainability, availability, waste and costs are another points of consideration. In late 2020, the Pre-Conceptual Design activities to develop the divertor of the European demonstration fusion reactor were officially concluded. On this occasion, the baseline design and the key technology options were identified and verified by the project team (EUROfusion Work Package Divertor) based on seven years of R&D efforts and endorsed by Gate Review Panel. In this paper, an overview of the load specifications, brief descriptions of the design and the highlights of the technology R&D work are presented together with the further work still needed