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Objective: This study tested the hypothesis that a neuroprotective combined therapy based on epidermal growth factor (EGF) and growth hormone-releasing hexapeptide (GHRP6) could be safe for acute ischemic stroke patients, admitting up to 30% of serious adverse events (SAE) with proven causality. Methods: Amulti-centric, randomized, open-label, controlled, phase I-II clinical trial with parallel groups was conducted (July 2017 to January 2018). Patients aged 18-80 years with a computed tomography-confirmed ischemic stroke and less than 12 h from the onset of symptoms were randomly assigned to the study groups I (75 µg rEGF + 3.5mg GHRP6 i.v., n=10), II (75 µg rEGF + 5mg GHRP6 i.v., n=10), or III (standard care control, n=16). Combined therapy was given BID for 7 days. The primary endpoint was safety over 6months. Secondary endpoints included neurological (NIHSS) and functional [Barthel index andmodified Rankin scale (mRS)] outcomes. Results: The study population had a mean age of 66 ± 11 years, with 21 men (58.3%), a baseline median NIHSS score of 9 (95% CI: 8-11), and a mean time to treatment of 7.3 ± 2.8 h. Analyses were conducted on an intention-to-treat basis. SAEs were reported in 9 of 16 (56.2%) patients in the control group, 3 of 10 (30%) patients in Group I (odds ratio (OR): 0.33; 95% CI: 0.06-1.78), and 2 of 10 (20%) patients in Group II (OR: 0.19; 95% CI: 0.03-1.22); only two events in one patient in Group I were attributed to the intervention treatment. Compliance with the study hypothesis was greater than 0.90 in each group. Patients treated with EGF + GHRP6 had a favorable neurological and functional evolution at both 90 and 180 days, as evidenced by the inferential analysis of NIHSS, Barthel, and mRS and by theirmoderate to strong effect size. At 6months, proportion analysis evidenced a higher survival rate for patients treated with the combined therapy. Ancillary analysis includingmerged treated groups and utility-weightedmRS also showed a benefit of this combined therapy. Conclusion: EGF + GHRP6 therapy was safe. The functional benefits of treatment in this study supported a Phase III study. [ABSTRACT FROM AUTHOR]

Probabilistic domain decomposition (PDD) is an alternative paradigm for solving boundary value problems (BVPs) in parallel with excellent scalability properties, thanks to its reliance on stochastic representations of the BVP. However, there are cases when the latter is less numerically convenient, or unknown. Semilinear elliptic BVPs and the Helmholtz equation are prominent examples of either class. In this paper, we overcome this issue by designing suitable iterative schemes for either problem. These schemes not only retain the desirable properties of PDD but also are optimally suited for pathwise variance reduction, resulting in a systematic, nearly cost-free reduction of the statistical error through the iterations. Numerical tests carried out on the supercomputer Marconi100 are presented. [ABSTRACT FROM AUTHOR]