Network extraction by routing optimization

Routing optimization is a relevant problem in many contexts. Solving directly this type of optimization problem is often computationally unfeasible. Recent studies suggest that one can instead turn this problem into one of solving a dynamical system of equations, which can instead be solved efficiently using numerical methods. This results in enabling the acquisition of optimal network topologies from a variety of routing problems. However, the actual extraction of the solution in terms of a final network topology relies on numerical details which can prevent an accurate investigation of their topological properties. In this context, theoretical results are fully accessible only to an expert audience and ready-to-use implementations for non-experts are rarely available or insufficiently documented. In particular, in this framework, final graph acquisition is a challenging problem in-and-of-itself. Here we introduce a method to extract networks topologies from dynamical equations related to routing optimization under various parameters' settings. Our method is made of three steps: first, it extracts an optimal trajectory by solving a dynamical system, then it pre-extracts a network and finally, it filters out potential redundancies. Remarkably, we propose a principled model to address the filtering in the last step, and give a quantitative interpretation in terms of a transport-related cost function. This principled filtering can be applied to more general problems such as network extraction from images, thus going beyond the scenarios envisioned in the first step. Overall, this novel algorithm allows practitioners to easily extract optimal network topologies by combining basic tools from numerical methods, optimization and network theory. Thus, we provide an alternative to manual graph extraction which allows a grounded extraction from a large variety of optimal topologies.Comment: 17 pages, 7 main Figures, 3 SI figure

Consensus definitions of 14 severe acute toxic effects for childhood lymphoblastic leukaemia treatment: a Delphi consensus

Although there are high survival rates for children with acute lymphoblastic leukaemia, their outcome is often counterbalanced by the burden of toxic effects. This is because reported frequencies vary widely across studies, partly because of diverse definitions of toxic effects. Using the Delphi method, 15 international childhood acute lymphoblastic leukaemia study groups assessed acute lymphoblastic leukaemia protocols to address toxic effects that were to be considered by the Ponte di Legno working group. 14 acute toxic effects (hypersensitivity to asparaginase, hyperlipidaemia, osteonecrosis, asparaginase-associated pancreatitis, arterial hypertension, posterior reversible encephalopathy syndrome, seizures, depressed level of consciousness, methotrexate-related stroke-like syndrome, peripheral neuropathy, high-dose methotrexate-related nephrotoxicity, sinusoidal obstructive syndrome, thromboembolism, and Pneumocystis jirovecii pneumonia) that are serious but too rare to be addressed comprehensively within any single group, or are deemed to need consensus definitions for reliable incidence comparisons, were selected for assessment. Our results showed that none of the protocols addressed all 14 toxic effects, that no two protocols shared identical definitions of all toxic effects, and that no toxic effect definition was shared by all protocols. Using the Delphi method over three face-to-face plenary meetings, consensus definitions were obtained for all 14 toxic effects. In the overall assessment of outcome of acute lymphoblastic leukaemia treatment, these expert opinion-based definitions will allow reliable comparisons of frequencies and severities of acute toxic effects across treatment protocols, and facilitate international research on cause, guidelines for treatment adaptation, preventive strategies, and development of consensus algorithms for reporting on acute lymphoblastic leukaemia treatment

Genetic predisposition to hemophagocytic lymphohistiocytosis: Report on 500 patients from the Italian registry.

BACKGROUND: Hemophagocytic lymphohistiocytosis (HLH) is a rare life-threatening disease affecting mostly children but also adults and characterized by hyperinflammatory features. A subset of patients, referred to as having familial hemophagocytic lymphohistiocytosis (FHL), have various underlying genetic abnormalities, the frequencies of which have not been systematically determined previously. OBJECTIVE: This work aims to further our understanding of the pathogenic bases of this rare condition based on an analysis of our 25 years of experience. METHODS: From our registry, we have analyzed a total of 500 unselected patients with HLH. RESULTS: Biallelic pathogenic mutations defining FHL were found in 171 (34%) patients; the proportion of FHL was much higher (64%) in patients given a diagnosis during the first year of life. Taken together, mutations of the genes PRF1 (FHL2) and UNC13D (FHL3) accounted for 70% of cases of FHL. Overall, a genetic diagnosis was possible in more than 90% of our patients with FHL. Perforin expression and the extent of degranulation have been more useful for diagnosing FHL than hemophagocytosis and the cytotoxicity assay. Of 281 (56%) patients classified as having "sporadic" HLH, 43 had monoallelic mutations in one of the FHL-defining genes. Given this gene dosage effect, FHL is not strictly recessive. CONCLUSION: We suggest that the clinical syndrome HLH generally results from the combined effects of an exogenous trigger and genetic predisposition. Within this combination, different weights of exogenous and genetic factors account for the wide disease spectrum that ranges from HLH secondary to severe infection to FHL.Supported by grants from Associazione Italiana Ricerca Istiocitosi (AIRI), Associazione Ciemmeesse-Girotondo per il Meyer, Ministero della Salute (Bando Malattie Rare RF-TOS-2008-1219488), and the Seventh Framework Programme (FP7) of the European Commission (“FIGHT-HLH” Project no. 306124 to M.A.). Disclosure of potential conflict of interest: D. Pende receives royalties paid to her institution. G. M. Griffiths has received research support from the Wellcome Trust. L. Luzzatto is on the Alexion Pharmaceuticals SAB and has received consultancy fees from GlaxoSmithKline.This is the final version of the article. It first appeared from Elsevier via http://dx.doi.org/10.1016/j.jaci.2015.06.04

Outcome of relapsed/refractory acute promyelocytic leukaemia in children, adolescents and young adult patients — a 25‐year Italian experience

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Risk factors for endocrine complications in transfusion-dependent thalassemia patients on chelation therapy with deferasirox: a risk assessment study from a multicentre nation-wide cohort

Transfusion-dependent patients typically develop iron-induced cardiomyopathy, liver disease, and endocrine complications. We aimed to estimate the incidence of endocrine disorders in transfusion-dependent thalassemia (TDT) patients during long-term iron-chelation therapy with deferasirox (DFX).We developed a multicentre follow-up study of 426 TDT patients treated with once-daily DFX for a median duration of 8 years, up to 18.5 years. At baseline, 118, 121, and 187 patients had 0, 1, or ≥2 endocrine diseases respectively. 104 additional endocrine diseases were developed during the follow-up. The overall risk of developing a new endocrine complication within 5 years was 9.7% (95%CI=6.3-13.1). Multiple Cox regression analysis identified 3 key predictors: age showed a positive log-linear effect (adjusted HR for 50% increase=1.2, 95%CI=1.1-1.3, P=0.005), the serum concentration of thyrotropin (TSH) showed a positive linear effect (adjusted HR for 1 mIU/L increase=1.3, 95%CI=1.1-1.4, P

Ecosistemi per la ricerca Atti Convegno ACNP/NILDE Trieste, 22-23 maggio 2014

Il secondo convegno congiunto ACNP / NILDE: ecosistemi per la ricerca è stato ospitato dal 22 al 23 maggio 2014 dall’Università di Trieste. Sotto gli auspici della stessa Università di Trieste e degli altri enti di ricerca del Friuli Venezia Giulia1 sono stati affrontati in un’ottica internazionale i temi del rapporto tra cataloghi collettivi e servizi interbibliotecari, e il più generale ambito dei servizi bibliografici per la ricerca scientifica. ACNP e NILDE possono essere considerati un vero e proprio ecosistema. Le biblioteche e i bibliotecari collaborano tra di loro in maniera reciproca e secondo modalità interconnesse, offrendo agli utenti servizi sempre più evoluti e dinamici. Questo ecosistema, essendo aperto, mette i propri servizi a disposizione della ricerca scientifica in senso generale. Il convegno di Trieste ha offerto l’occasione di investigare e proporre soluzioni innovative, interconnessioni e relazioni nuove e più proficue. Il convegno ha presentato alcune rilevanti esperienze internazionali in tema di servizi interbibliotecari e cataloghi collettivi e la prosecuzione di attività che erano state proposte come spunti di ispirazione nel convegno precedente2 inoltre si sono condotte delle riflessioni sulle nuove esigenze dell’utenza. Una ultima parte è dedicata alla illustrazione degli sviluppi tecnici e le prospettive future di ACNP e di NILDE. Hanno partecipato all’evento oltre 200 colleghi italiani e stranieri ed i relatori dei 18 contributi provenivano da Italia, Germania, Austria, Grecia, Slovenia e Stati Uniti. Il carattere di confronto e di condivisione delle esperienze tipico della realtà partecipativa di ACNP e NILDE, è emerso anche in questa occasione nella tavola rotonda - di cui viene riportato un resoconto dettagliato - che ha affrontato il tema della valutazione della ricerca dal punto di vista delle biblioteche. Inoltre, la molto partecipata sessione poster ha ospitato 13 lavori- anch’essi riportati nel volume - incentrati oltre che su ACNP e NILDE anche sul tema ricerca e sistema biblioteca, dando ottimi spunti di partecipazione, dialogo e confronto sulle diverse realtà in cui operiamo