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Ustekinumab (UST), a human anti-IL12/23p40 monoclonal antibody, was approved by FDA and EMA for the treatment of moderate to severe Crohn's disease (CD). Whether UST is effective in inducing deep remission, including mucosal healing and transmural healing, in patients with CD in a real life setting is not completely clear. This study was performed on 92 subjects with confirmed diagnosis of moderate to severe Crohn's disease and no neoplasia. Before inclusion, all patients had been exposed and had failed to respond to conventional and/or at least one biological therapy. All patients underwent endoscopic examination and bowel MRI and ultrasonography at baseline (T0). At week 52 (T52), patients underwent colonoscopy for assessment of mucosal healing and MRI or ultrasonography for assessment of transmural healing. CDAI was used for the assessment of clinical response and clinical remission. SES-CD was used to assess endoscopic response and remission. Incidence of treatment-related adverse events (TRAEs) was recorded during the study period. Clinical response at week 52 was achieved in 38 (50.5%) patients and clinical remission in 29 (39%). Twenty-six (34%) patients showed mucosal healing, 34 (45%) showed partial endoscopic response. We observed a reduction in SES-CD of at least 50% in 34 (45%) patients as well as an SES-CD ≤ 2 in 26 (35%) patients. All patients with mucosal healing also showed transmural healing. No major TRAEs were observed during treatment. In this multicenter, real life study, we show that UST was well tolerated and effective in inducing clinical response and clinical remission in patients with moderate to severe CD who had previously failed to respond to conventional or biologic therapy. UST showed limited efficacy in inducing deep remission (i.e. mucosal+transmural healing). [ABSTRACT FROM AUTHOR]

A stochastic approach is proposed, aiming at the optimal allocation of increasing sets of monitoring stations for the early detection of the intentional contamination of water distribution networks. The approach is based on the use of the Monte Carlo technique for the generation of a number of time-varying hydraulic scenarios, each consisting of a succession of steady conditions related to different users’ water demands. Given a time-varying hydraulic scenario, and chosing an injection node, the spreading of the contaminant through the network is evaluated by means of a Lagrangian advection model, and the arrival times to all the potential monitoring stations are calculated. If these operations are accomplished for all the source nodes, and for each of the time-varying hydraulic scenarios, a statistical analysis allows for the allocation of the monitoring stations which maximise the number of upstream nodes characterised by arrival times less than a pre-assigned value ( early warning time ). [ABSTRACT FROM AUTHOR]