Parameter setting highly affects the performance of Ant Colony Optimization (ACO) algorithms which inspired us to develop a module to be added to the standard Ant Colony System (ACS) algorithm by which the parameter-setting is done automatically. The module we added to the algorithm is a Fuzzy Logic Controller (FLC) which is used to tune the parameters according to robust performance measures of the algorithm. The parameter-tuning is performed as the algorithm runs, and this allows the dynamic setting of the parameters based on the current performance of the algorithm. The adaptive ACS algorithm was tested on many TSP problems with different sizes and the results were compared to those of the standard algorithm, where this comparison showed that the adaptive ACS algorithm outperformed the standard algorithm and reached near-optimal solutions that the standard algorithm could not find. It also showed a faster convergence to the solutions than the standard algorithm.

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Background In small-size and short term studies of hepatitis C virus (HCV)-cryoglobulinemia vasculitis (CryoVas), direct antiviral agents (DAAs) showed a better response rate and tolerance than interferon containing regimens.Objectives To evaluate the effectiveness and tolerance of all oral interferon-free DAA in a large CryoVas cohort with long-term follow-up.Methods This prospective international multicenter cohort study included 148 symptomatic HCV-CryoVas patients (53.7% with cirrhosis and 49.3% antiviral-na{\"ıve). They all received DAA, i.e. sofosbuvir (SOF) plus daclatasvir (n=53), SOF plus ribavirin (n=51), SOF plus ledipasvir (n=23), or SOF plus simeprevir (n=18), for 12 or 24 weeks. The primary endpoint was the clinical response of CryoVas symptoms at week 12 after stopping DAAs.Results 106 (72.6%) patients showed a complete response, 33 (22.6%) a partial response and 7 (4.8%) no response of CryoVas symptoms. Cryoglobulinemia was no longer found in 53.1%. A sustained virological response was obtained in 97.2%. Premature DAA withdrawal was noted in 4.1%. Two factors were associated with a poor response: a severe form of CryoVas [OR 0.33, 95% CI: 0.12 to 0.91; p=0.03] and peripheral neuropathy [OR 0.31, 95% CI: 0.11 to 0.84; p=0.02]. After a median follow-up of 15.3 months, 4 (2.8%) patients died. The final clearance rates of CryoVas manifestations were as follows: purpura (97.2%), renal involvement (91.5%), arthralgia (85.7%), neuropathy (77.1%) and cryoglobulinemia (53.8%). Only SOF plus ledipasvir regimen showed significant superiority [OR 4.09, 95% CI: 1.19 to 19.00; p=0.04].Conclusions The different DAA combinations showed high response rates of HCV-CryoVas symptoms. The tolerance was good, and the mortality rate was very low. We identified prognosis factors of response to DAA.Disclosure of Interest P. Cacoub Consultant for: Janssen, BMS, Abbvie, GSK, Astra zeneka, Gilead, Merck, Roche, Servier, Vifor, S. N. Si ahmed Consultant for: BMS, Abbvie, Gilead, Roche, Janssen, Y. ferfar: None declared, S. Pol Consultant for: Sanofi, Novartis, Vertex, Boehringer, Janssen, BMS, Abbvie, GSK, Astra zeneka, Gilead, Merck, Roche, Servier, Vifor, D. Thabut: None declared, C. Hezode Consultant for: BMS, Merck, Abbvie, Gilead, Roche, Janssen, L. Alric Consultant for: BMS, Abbvie, Gilead, Janssen, Merck, C. Comarmond: None declared, G. Ragab: None declared, L. Quatuccio: None declared, M. Hegazy: None declared, T. Poynard: None declared, M. Resche Rigon: None declared, D. Saadoun Consultant for: medimmune, BMS, Abbvie, GSK, Astra zeneka, Gilead, Merck, Roche, Servier,

Musculoskeletal infection remains a great challenge in orthopedic and trauma surgery. Despite best medical and surgical practice and significant advances in research and development, bone and implant associated infections are still difficult to diagnose, impossible to prevent in all cases and require invasive and debilitating treatment. The development and safe clinical implementation of novel preventative, therapeutic or diagnostic strategies requires the use of animal models of infection, which provide crucial evidence regarding performance, cytocompatibility, biocompatibility, and safety prior to clinical implementation.
Many animal models of musculoskeletal infection have been described in the literature; however, there remains a dearth of fully standardized or universally accepted reference models hindering advancement in the field. The following chapter provides an overview of the animal models available for the study of musculoskeletal infection, the latest advances that are expected to improve them, and some of the most important scientific output achieved using these models.