Decentralized Triangular Guidance Algorithms for Formations of UAVs

This paper deals with the design of a guidance control system for a swarm of unmanned aerial systems flying at a given altitude, addressing flight formation requirements that can be formulated constraining the swarm to be on the nodes of a triangular mesh. Three decentralized guidance algorithms are presented. A classical fixed leader–follower scheme is compared with two alternative schemes: the former is based on the self-identification of one or more time-varying leaders; the latter is an algorithm without leaders. Several operational scenarios have been simulated involving swarms with obstacles and an increasing number of aircraft in order to prove the effectiveness of the proposed guidance schem

WIN55,212-2-induced expression of Mir-29b1 favours the suppression of osteosarcoma cell migration in a SPARC-independent manner

WIN55,212-2 (WIN) is a synthetic agonist of cannabinoid receptors that displays promising antitumour properties. The aim of this study is to demonstrate that WIN is able to block the migratory ability of osteosarcoma cells and characterize the mechanisms involved. Using wound healing assay and zymography, we showed that WIN affects cell migration and reduces the activity of the metalloproteases MMP2 and MMP9. This effect seemed to be independent of secreted protein acidic and rich in cysteine (SPARC), a matricellular protein involved in tissue remodeling and extracellular matrix deposition. SPARC release was indeed prevented by WIN, and SPARC silencing by RNA interference did not influence the effect of the cannabinoid on cell migration. WIN also increased the release of extracellular vesicles and dramatically upregulated miR-29b1, a key miRNA that modulates cell proliferation and migration. Interestingly, reduced cell migration was observed in stably miR-29b1-transfected cells, similarly to WIN-treated cells. Finally, we show the absence of SPARC in the extracellular vesicles released by osteosarcoma cells and no changes in SPARC level in miR-29b1 overexpressing cells. Overall, these findings suggest that WIN markedly affects cell migration, dependently on miR-29b1 and independently of SPARC, and can thus be considered as a potential innovative therapeutic agent in the treatment of osteosarcoma

Central venous catheter insertion: a bedside procedure for haematological patients.

The present management of onco-haematologic patients may require continuous infusion of cytotoxic drugs, use of drugs or concentrated ion solutions which are toxic for the endothelial wall of small vessels, infusion of large amounts of antibiotics or antimycotics, red blood cell and platelet transfusion, and not rarely parenteral nutrition. Such a complex therapy needs a vascular access by a central vein catheter (CVC) insertion. Many types of CVC are available at present: tunnelled Hickman or Hickmanlike catheters, subcutaneous ports, tunnelled catheters with Groshong valve, external untunnelled catheters

CV19022

This report provides the main results of the 2019 underwater television survey on the ‘Labadie, Jones and Cockburn Banks’ ICES assessment area; Functional Unit 20-21. The 2019 survey was multi-disciplinary in nature collecting UWTV, and other ecosystem data. A total of 95 UWTV stations were completed at 6 nm intervals over a randomised isometric grid design. The mean burrow density was 0.06 burrows/m2 compared with 0.27 burrows/m2 in 2018. The 2019 geostatistical abundance estimate was 617 million, a 77% decrease on the abundance for 2018, with a CV of 5% which is well below the upper limit of 20% recommended by SGNEPS 2012. Low densities were observed throughout the ground. Using the 2019 estimate of abundance and updated stock data implies catch in 2020 that correspond to the F ranges in the EU multi annual plan for Western Waters are between 1131 and 1150 tonnes (assuming that discard rates and fishery selection patterns do not change from the average of 2016–2018). One species of sea-pen (Virgularia mirabilis) were recorded as present at the stations surveyed. Trawl marks were observed at 32% of the stations surveyed

Patients with paroxysmal nocturnal hemoglobinuria have a high frequency of peripheral-blood T cells expressing activating isoforms of inhibiting superfamily receptors

Patients with paroxysmal nocturnal hemoglobinuria (PNH) have a large clonal population of blood cells deriving from hematopoietic stem cells (HSCs) deficient in glycosylphosphatidylinositol (GPI)-anchored surface molecules. A current model postulates that PNH arises through negative selection against normal HSCs exerted by autoreactive T cells, whereas PNH HSCs escape damage. We have investigated the inhibitory receptor superfamily (IRS) system in 13 patients with PNH. We found a slight increase in the proportion of T cells expressing IRS. In contrast to what applies to healthy donors, the engagement of IRS molecules on T cells from patients with PNH elicited a powerful cytolytic activity in a redirected killing assay, indicating that these IRSs belong to the activating type. This was confirmed by clonal analysis: 50% of IRS+ T-cell clones in patients with PNH were of the activating type, while only 5% were of the activating type in healthy donors. Moreover, the ligation of IRS induces (1) production of tumor necrosis factor alpha (TNF-alpha) and interferon gamma (IFN-gamma) and (2) brisk cytolytic activity against cells bearing appropriate IRS counter-ligands. In addition, these IRS+ T cells show natural killer (NK)-like cytolytic activity to which GPI- cells were less sensitive than GPI+ cells. Thus, T cells with NK-like features, expressing the activating isoforms of IRS, may include effector cells involved in the pathogenesis of PNH

High prevalence of hepatitis C virus infection in patients with B-cell lymphoproliferative disorders in Italy.

Starting from the observation that a number of consecutive patients with non-Hodgkin's lymphoma (NHL) resulted positive for hepatitis C virus (HCV) antibodies on routine testing, we set up a survey for HCV contact prevalence in all patients with lymphoproliferative disorders (LPD) followed in our institution. We searched for HCV antibodies by a thirdgeneration ELISA technique, followed by a confirmation test (RIBA III); serum viral RNA and HCV genotype were investigated by a RT-PCR technique. We screened a total of 315 patients suffering from B-NHL (91), multiple myeloma (56), MGUS (48), chronic lymphocytic leukemia (57), Waldentrom's macroglobulinemia (13), Hodgkin's disease (HD)(43), and T-NHL (9). While only I of 52 patients with a non-B-LPD (HD or T-NHL) had signs of HCV contact (i.e., 1.9%, which is in the range of the normal population in the South of Italy), 59 of 263 patients with a B-LPD (22.4%) had HCV antibodies or RNA, or both, with no major differences among the various types of disorders, except for WM, in which the rate was higher (61.5%). The same prevalence was found for patients tested at diagnosis or during the follow-up, and in transfused or never-transfused patients. Only a few patients were aware of having a liver disease; one-half of HCV-positive patients never had transaminase increase. A review of data from Central and Northern Italy is included, showing similar findings; a report from Japan has confirmed such an association, while limited surveys in England have not revealed any correlation. These findings may have important biological and clinical implications

Cost-Utility Analysis Comparing Pegcetacoplan to Anti-C5 Monoclonal Antibodies in the Treatment of Paroxysmal Nocturnal Hemoglobinuria

Sergio Di Matteo,1 Roberto Freilone,2 Giacomo Matteo Bruno,1,3 Rosario Notaro,4 Sabrin Moumene,1 Nicoletta Martone,5 Cristina Teruzzi,5 Antonio Ciccarone,1 Giorgio Lorenzo Colombo1,3 1Center of Research, SAVE Studi - Health Economics and Outcomes Research, Milan, Italy; 2Dipartimento di Oncologia - Direttore SC Ematologia, Azienda Ospedaliera Universitaria Città della Salute e della Scienza, Torino e componente Tumor Molecular Board (TMB) Regione Piemonte, Torino, Italy; 3Department of Drug Sciences, University of Pavia, Pavia, Italy; 4Direttore S.C. Core Research Laboratory in ISPRO, Firenze, Italy; 5Sobi S.r.l., Milano, ItalyCorrespondence: Giorgio Lorenzo Colombo, Email [email protected]: Paroxysmal nocturnal hemoglobinuria is a rare, acquired disease characterized by hemolytic episodes and associated with significant clinical burden. The introduction of C5 inhibitory monoclonal antibodies (C5i) represented a major breakthrough in PNH treatment, effectively reducing intravascular hemolysis (IVH) but showing limited impact on extravascular hemolysis (EVH). In 2021, the C3 inhibitor pegcetacoplan was approved by EMA and recently reimbursed in Italy, which also has the advantages in the reduction of both IVH and EVH, increasing hemoglobin values and simultaneously improving the quality of life and fatigue of patients. A cost-utility analysis was developed to compare pegcetacoplan to C5i (eculizumab and ravulizumab) in the PNH population who remain anemic after treatment with C5i for at least 3 months.Materials and Methods: The analysis employed a Markov model with a 5-year time horizon whereby patients can transition among 3 PNH health states, adopting the perspective of the Italian NHS. Efficacy data were sourced from the PEGASUS study, with drug prices reflecting ex-factory costs. Additionally, costs associated with resource utilization, adverse events, and complications were estimated based on outpatient and hospital care rates, excluding indirect expenses. Utility and disutility values related to transfusions were also considered, with pegcetacoplan allowing for dose escalation.Results: The cumulative cost of treatment per individual patient at 5 years was estimated to be € 1,483,454 for pegcetacoplan, € 1,585,763 for eculizumab, and € 1,574,826 for ravulizumab. Pegcetacoplan demonstrated a superior increase in quality-adjusted life years (QALYs) compared to both eculizumab (0.51 increase) and ravulizumab (0.27 increase). Furthermore, pegcetacoplan showed a reduction in complication management costs (€ 22,891 less compared to eculizumab and € 22,611 less compared to ravulizumab) and lower transfusion-related expenses (€ 14,147 less than both C5i treatments).Conclusion: Pegcetacoplan emerged as the dominant strategy in this analysis, being more effective, less expensive and improves quality of life in the analyzed population affected by PNH.Keywords: PNH, pegcetacoplan, eculizumab, ravulizumab, IVH, EVH, cost-utility analysis, pharmacoeconomic