Abstract-Hypertension, diabetes, and hypercholesterolemia are characterized by a reduction in arterial distensibility and by accelerated atherosclerosis. Whether arterial stiffening is an inherent feature of these conditions or just the consequence of the atherosclerotic clinical or subclinical lesions is not known, however. Our aim was to obtain information on this issue by directly measuring, in humans, arterial distensibility both at the site of an atherosclerotic lesion and at the proximal normal site. In 10 patients (8 men; meanϮSEM age, 65.2Ϯ3.4 years) affected by monolateral hemodynamic significant internal carotid artery stenosis, we measured arterial distensibility (Wall Track System; PIE Medical) bilaterally, both at the internal carotid artery and at the common carotid artery level. In the common carotid artery, measurements were made 3 cm below the bifurcation. In the affected internal carotid artery, measurements were made at the plaque shoulder (wall thickness of 2 mm). Measurements were made in the contralateral internal carotid artery at a symmetrical level. Arterial wall thickness was measured in the same site of arterial distensibility. Arterial distensibility was less in the internal than in the common carotid artery, with a marked reduction at the plaque internal carotid artery level compared with the corresponding contralateral site (Ϫ45%, PϽ0.01). It was also less, however, in the common carotid artery branching into the atherosclerotic internal carotid artery than in the contralateral common carotid artery (Ϫ25%, PϽ0.05). Wall thickness was similar in the 2 common carotid arteries and obviously greater in the affected internal carotid artery than in the contralateral artery. Arterial distensibility was markedly less in the internal carotid artery where there was a plaque compared with the intact contralateral internal carotid artery; it was also less, however, in the common carotid artery of the affected side in comparison with the contralateral common carotid artery. This provides evidence that the effect of a plaque on arterial mechanical properties is not limited to the actual plaque site but rather extends to a considerable degree in a proximal direction. Key Words: arteries Ⅲ atherosclerosis Ⅲ plaque S everal studies have shown that conditions such hypertension, diabetes, and, to a lesser extent, hypercholesterolemia are characterized by a reduction in arterial distensibility. [1][2][3][4] This has clinical implications because studies in animals have reported a reduction in arterial distensibility to be accompanied by accelerated atherosclerosis, possibly because arterial stiffening increases the traumatic effect of intravascular pressure on the vessel wall. 5 In hypertension, diabetes, and hypercholesterolemia, atherosclerosis starts before the appearance of the clinical complications of these conditions. This poses the question of whether arterial stiffening is an inherent feature of these conditions or just the consequence of the atherosclerotic lesions. In the present study, our ...

We consider Reinforcement Learning (RL) problems where an agent attempts to maximize a reward signal while minimizing a cost function that models unsafe behaviors. Such formalization is addressed in the literature using constrained optimization on the cost, limiting the exploration and leading to a significant trade-off between cost and reward. In contrast, we propose a Safety-Oriented Search that complements Deep RL algorithms to bias the policy toward safety within an evolutionary cost optimization. We leverage evolutionary exploration benefits to design a novel concept of safe mutations that use visited unsafe states to explore safer actions. We further characterize the behaviors of the policies over desired specifics with a sample-based bound estimation, which makes prior verification analysis tractable in the training loop. Hence, driving the learning process towards safer regions of the policy space. Empirical evidence on the Safety Gym benchmark shows that we successfully avoid drawbacks on the return while improving the safety of the policy.

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