The combination of primary sclerosing cholangitis and CCR5-Delta 32 in recipients is strongly associated with the development of nonanastomotic biliary strictures after liver transplantation

Background: The role of the immune system in the pathogenesis of nonanastomotic biliary strictures (NAS) after orthotopic liver transplantation (OLT) is unclear. A loss-of-function mutation in the CC chemokine receptor 5 (CCR5-Delta 32) leads to changes in the immune system, including impaired chemotaxis of regulatory T cells. Aim: To investigate the impact of the CCR5-Delta 32 mutation on the development of NAS. Methods: In 384 OLTs, we assessed the CCR5 genotype in donors and recipients and correlated this with the occurrence of NAS. Results: The CCR5-Delta 32 allele was found in 65 (16.9%) recipients. The cumulative incidence of NAS at 5 years was 6.5% in wild-type (Wt) recipients vs 17.2% for carriers of the CCR5-Delta 32 allele (P 2 years after OLT, compared with 10% in the Wt group. In multivariate regression analysis, the adjusted risk of developing NAS was four-fold higher in recipients with CCR5-Delta 32 (P <0.01). The highest risk of NAS was seen in patients transplanted for primary sclerosing cholangitis (PSC), who also carried CCR5-Delta 32 (relative risk 5.4, 95% confidence interval 2.2-12.9; P <0.01). Donor CCR5 genotype had no impact on the occurrence of NAS. Conclusions: Patients with the CCR5-Delta 32 mutation have a four-fold higher risk of developing NAS, compared with Wt recipients. This risk is even higher in patients with CCR5-Delta 32 transplanted for PSC. Late development of NAS is significantly more present in patients with CCR5-Delta 32. These data suggest that the immune system plays a critical role in the development of NAS after OLT

Influence of Tire Parameters on ABS Performance

The antilock braking system (ABS) is an active control system, which prevents the wheels from locking-up during severe braking. The ABS control cycle rapidly modulates braking pressure at each wheel mainly based on tire peripheral acceleration. Significant wheel speed oscillations and consequent fast variations of tire longitudinal slip are a consequence, which, in turn, produce a corresponding variation of tire longitudinal force according to the ABS control cycle. Clearly, tire characteristics, namely, tire peak friction (regulating maximum vehicle deceleration), longitudinal stiffness, optimal slip ratio, curvature factor (regulating the position of the peak of μ-slip curve and the subsequent drop), and relaxation length (accounting for tire dynamic response) may significantly influence ABS performance. The aim of the present paper is to evaluate the effect of the main tire parameters on ABS performance. This task is, however, very challenging, since tire characteristics are intrinsically related, and the analysis involves interaction between tires, vehicle, and ABS control logic. A methodology based on the hardware-in-the-loop (HiL) technique is used. This approach was selected to overcome limitations of numerical simulations or difficulties related to the execution of onroad experimental tests (repeatability, costs, etc.). The developed HiL test bench includes all the physical elements of the braking system of a vehicle (comprising the ABS control unit) and a 14 degrees of freedom (dofs) vehicle model, which are synchronized by a real-time board. With the developed HiL test bench, a sensitivity analysis was carried out to assess the influence of tire peak friction, longitudinal stiffness, and relaxation length on ABS performance, evaluated in terms of braking distance, mean longitudinal acceleration, and energy distribution