Refinement of the diagnostic approach for the identification of children and adolescents affected by familial hypercholesterolemia: Evidence from the LIPIGEN study

Background and aims: We aimed to describe the limitations of familiar hypercholesterolemia (FH) diagnosis in childhood based on the presence of the typical features of FH, such as physical sings of cholesterol accumulation and personal or family history of premature cardiovascular disease or hypercholesterolemia, comparing their prevalence in the adult and paediatric FH population, and to illustrate how additional information can lead to a more effective diagnosis of FH at a younger age. Methods: From the Italian LIPIGEN cohort, we selected 1188 (≥18 years) and 708 (<18 years) genetically-confirmed heterozygous FH, with no missing personal FH features. The prevalence of personal and familial FH features was compared between the two groups. For a sub-group of the paediatric cohort (N = 374), data about premature coronary heart disease (CHD) in second-degree family members were also included in the evaluation. Results: The lower prevalence of typical FH features in children/adolescents vs adults was confirmed: the prevalence of tendon xanthoma was 2.1% vs 13.1%, and arcus cornealis was present in 1.6% vs 11.2% of the cohorts, respectively. No children presented clinical history of premature CHD or cerebral/peripheral vascular disease compared to 8.8% and 5.6% of adults, respectively. The prevalence of premature CHD in first-degree relatives was significantly higher in adults compared to children/adolescents (38.9% vs 19.7%). In the sub-cohort analysis, a premature CHD event in parents was reported in 63 out of 374 subjects (16.8%), but the percentage increased to 54.0% extending the evaluation also to second-degree relatives. Conclusions: In children, the typical FH features are clearly less informative than in adults. A more thorough data collection, adding information about second-degree relatives, could improve the diagnosis of FH at younger age

Hybrid cancellation of ripple disturbances arising in AC/DC converters

In AC/DC converters, a peculiar periodic nonsmooth waveform arises, the so-called ripple. In this paper we propose a novel model that captures this nonsmoothness by means of a hybrid dynamical system performing state jumps at certain switching instants, and we illustrate its properties with reference to a three phase diode bridge rectifier. As the ripple corrupts an underlying desirable signal, we propound two observer schemes ensuring asymptotic estimation of the ripple, the first with and the second without knowledge of the switching instants. Our theoretical developments are well placed in the context of recent techniques for hybrid regulation and constitute a contribution especially for our second observer, where the switching instants are estimated. Once asymptotic estimation of the ripple is achieved, the ripple can be conveniently canceled from the desirable signal, and thanks to the inherent robustness properties of the proposed hybrid formulation, the two observer schemes require only that the desirable signal is slowly time varying compared to the ripple. Exploiting this fact, we illustrate the effectiveness of our second hybrid observation law on experimental data collected from the Joint European Torus tokamak