Background: Heterozygous Familial Hypercholesterolemia (FH) represents the most frequent monogenic disorder with an estimated prevalence of 1:250 in the general population. Diagnosis during childhood enables early initiation of preventive measures, reducing the risk of severe consecutive atherosclerotic manifestations. Nevertheless, population-based screening programs for FH are scarce.Methods: In the VRONI study children aged 5 to 14 years in Bavaria are invited to participate in a FH screening program during regular pediatric visits. The screening is based on LDL-C measurements from capillary blood. If exceeding 130 mg/dl (3.34 mmol/l), i.e. the expected 95th percentile in this age group, subsequent molecular genetic analysis for FH is performed. Children with FH pathogenic variants enter a registry and are treated by specialized pediatricians. Furthermore, qualified training centers offer FH-focused training courses to affected families. For first degree relatives, reverse cascade screening is recommended to identify and treat affected family members.Results: Implementation of VRONI required intensive prearrangements for addressing ethical, educational, data-safety, legal and organisational aspects, which will be outlined in this paper. Recruitment started in January of 2021, within two months more than 280 pediatricians screened over 1,150 children. Approximately 60,000 children are expected to be enrolled in the VRONI study until 2024. Conclusion: VRONI aims to test the feasibility of a population-based screening for FH in children in Bavaria, intending to set the stage for a nation-wide FH screening infrastructure. Further we aim to validate genetic variants of unclear significance, detect novel causative mutations, and contribute to polygenic risk indices. (German Clinical Trials Register: DRKS00022140; registered August 21st2020.)

The dynamical principle for a population of interacting individuals with mutual pairwise knowledge, presented by the author in a previous paper for the case of constant knowledge, is extended to include the possibility that the knowledge is timedependent. Several mechanisms are presented by which the mutual knowledge, represented by a matrix K, can be altered, leading to dynamical equations for K(t). We present various examples of the transient and long time asymptotic behavior of K(t) for populations of relatively isolated individuals interacting infrequently in local binary collisions. Among the effects observed in the numerical experiments are knowledge diffusion, learning transients, and fluctuating equilibria. Evidence of metastable states and intermittant switching leads us to envision a spectroscopy associated with such transitions that is independent of the specific physical individuals and the population. Such spectra may serve as good lumped descriptors of the collective emergent behavior of large classes of populations in which mutual knowledge is an important part of the dynamics.

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