No abstract

Abstract-This paper presents the design and implementation of a new control strategy for Ghent University, Ghent, Belgium (UGent) knee rig, which is capable of imposing bicycle motions on cadaver knee specimens in order to investigate knee biomechanics and the impact of newly designed knee implants. An electromechanical description of the system with its instrumentation and limitations is given. Via system identification, a dynamical model of the multipleinput/multiple-output system is obtained on which the control strategy design is based. This control strategy combines position control and force control. Dynamical analysis of the system suggests the need for a Proportional-IntegralDerivative (PID) control strategy with gain adaptation. In order to fulfill the performance specifications, a feed-forward action and decouplers are added to the control strategy, and their advantages are shown via simulations and experiments. The complete strategy is implemented on the real system and the output signals are measured for analysis. The results indicate that the identified model fits well to the measured data and that the designed control strategy is able to accurately control the system. The measurements show that the predefined performance specifications have been achieved for a bicycle motion with a period of 10 s; the error on the position is smaller than 2 mm and the error on the force is smaller than 10 N.

No abstract

No abstract

Background We previously reported that impaired type I IFN activity, due to inborn errors of TLR3- and TLR7-dependent type I interferon (IFN) immunity or to autoantibodies against type I IFN, account for 15–20% of cases of life-threatening COVID-19 in unvaccinated patients. Therefore, the determinants of life-threatening COVID-19 remain to be identified in ~ 80% of cases. Methods We report here a genome-wide rare variant burden association analysis in 3269 unvaccinated patients with life-threatening COVID-19, and 1373 unvaccinated SARS-CoV-2-infected individuals without pneumonia. Among the 928 patients tested for autoantibodies against type I IFN, a quarter (234) were positive and were excluded. Results No gene reached genome-wide significance. Under a recessive model, the most significant gene with at-risk variants was TLR7, with an OR of 27.68 (95%CI 1.5–528.7, P = 1.1 × 10−4) for biochemically loss-of-function (bLOF) variants. We replicated the enrichment in rare predicted LOF (pLOF) variants at 13 influenza susceptibility loci involved in TLR3-dependent type I IFN immunity (OR = 3.70[95%CI 1.3–8.2], P = 2.1 × 10−4). This enrichment was further strengthened by (1) adding the recently reported TYK2 and TLR7 COVID-19 loci, particularly under a recessive model (OR = 19.65[95%CI 2.1–2635.4], P = 3.4 × 10−3), and (2) considering as pLOF branchpoint variants with potentially strong impacts on splicing among the 15 loci (OR = 4.40[9%CI 2.3–8.4], P = 7.7 × 10−8). Finally, the patients with pLOF/bLOF variants at these 15 loci were significantly younger (mean age [SD] = 43.3 [20.3] years) than the other patients (56.0 [17.3] years; P = 1.68 × 10−5). Conclusions Rare variants of TLR3- and TLR7-dependent type I IFN immunity genes can underlie life-threatening COVID-19, particularly with recessive inheritance, in patients under 60 years old.