Familial hypercholesterolaemia in children and adolescents from 48 countries: a cross-sectional study

Background: Approximately 450 000 children are born with familial hypercholesterolaemia worldwide every year, yet only 2·1% of adults with familial hypercholesterolaemia were diagnosed before age 18 years via current diagnostic approaches, which are derived from observations in adults. We aimed to characterise children and adolescents with heterozygous familial hypercholesterolaemia (HeFH) and understand current approaches to the identification and management of familial hypercholesterolaemia to inform future public health strategies. Methods: For this cross-sectional study, we assessed children and adolescents younger than 18 years with a clinical or genetic diagnosis of HeFH at the time of entry into the Familial Hypercholesterolaemia Studies Collaboration (FHSC) registry between Oct 1, 2015, and Jan 31, 2021. Data in the registry were collected from 55 regional or national registries in 48 countries. Diagnoses relying on self-reported history of familial hypercholesterolaemia and suspected secondary hypercholesterolaemia were excluded from the registry; people with untreated LDL cholesterol (LDL-C) of at least 13·0 mmol/L were excluded from this study. Data were assessed overall and by WHO region, World Bank country income status, age, diagnostic criteria, and index-case status. The main outcome of this study was to assess current identification and management of children and adolescents with familial hypercholesterolaemia. Findings: Of 63 093 individuals in the FHSC registry, 11 848 (18·8%) were children or adolescents younger than 18 years with HeFH and were included in this study; 5756 (50·2%) of 11 476 included individuals were female and 5720 (49·8%) were male. Sex data were missing for 372 (3·1%) of 11 848 individuals. Median age at registry entry was 9·6 years (IQR 5·8-13·2). 10 099 (89·9%) of 11 235 included individuals had a final genetically confirmed diagnosis of familial hypercholesterolaemia and 1136 (10·1%) had a clinical diagnosis. Genetically confirmed diagnosis data or clinical diagnosis data were missing for 613 (5·2%) of 11 848 individuals. Genetic diagnosis was more common in children and adolescents from high-income countries (9427 [92·4%] of 10 202) than in children and adolescents from non-high-income countries (199 [48·0%] of 415). 3414 (31·6%) of 10 804 children or adolescents were index cases. Familial-hypercholesterolaemia-related physical signs, cardiovascular risk factors, and cardiovascular disease were uncommon, but were more common in non-high-income countries. 7557 (72·4%) of 10 428 included children or adolescents were not taking lipid-lowering medication (LLM) and had a median LDL-C of 5·00 mmol/L (IQR 4·05-6·08). Compared with genetic diagnosis, the use of unadapted clinical criteria intended for use in adults and reliant on more extreme phenotypes could result in 50-75% of children and adolescents with familial hypercholesterolaemia not being identified. Interpretation: Clinical characteristics observed in adults with familial hypercholesterolaemia are uncommon in children and adolescents with familial hypercholesterolaemia, hence detection in this age group relies on measurement of LDL-C and genetic confirmation. Where genetic testing is unavailable, increased availability and use of LDL-C measurements in the first few years of life could help reduce the current gap between prevalence and detection, enabling increased use of combination LLM to reach recommended LDL-C targets early in life

IPv6 @ HH

The aim of this thesis project to design and implement a campus network based on IPv6, as IPv6 is the protocol of the future communication.There are many papers available which discuss upgrade from IPv4 to IPv6 and their side by side implementations and functionalities. Contrary to this we are working on running a network entirely based on IPv6. So we built this network infrastructure, monitored it and tested it.A network working on IPv6 is not just about a different addressing plan. Rather there are some serious questions. Network administrators are quite happy and comfortable with the current setup of IPv4. Would this IPv6 be able to provide them same facilities on one-to-one basis? If not, would it be upgrade or degrade on some functionality? Is there solution to every problem available or they would have to discover it themselves? All these and many more questions were faced and tackled in the course of this thesis

Low complexity constrained control using higher degree Lyapunov functions

International audienceExplicit Model Predictive Control often has a complex solution in terms of the number of regions required to define the solution and the corresponding memory requirement to represent the solution in the online implementation. An alternative approach to constrained control is based on the use of controlled contractive sets. However, polytopic controlled contractive sets may themselves be relatively complex, leading to a complex explicit solution, and the polytopic structure can limit the size of the controlled contractive set. This paper develops a method to obtain a larger controlled contractive set by allowing higher order functions in the definition of the contractive set, and explores the use of such higer-order contractive sets in controller design leading to a low complexity explicit control formulation

Controlled contractive sets for low-complexity constrained control

International audienceExplicit constrained control is relatively simple when a controlled contractive set is available. However, the complexity of the explicit controller will depend on the complexity of the controlled contractive set. The ability to design a low complexity controlled contractive set is therefore desirable. Most methods for finding controlled contractive sets either assume the use of a constant linear state feedback, or is based on reachable set computations. In the first case, the assumption of a constant linear state feedback is restrictive (as MPC controllers for linear systems are typically piecewise affine), and in the second case the complexity of the controlled contractive set may be very high. Initial results on the construction of low complexity controlled contractive sets without assuming linear state feedback were reported at the IFAC World Congress in 2014. The present paper addresses shortcomings in the previous results, including the ability to handle identical modes in series (corresponding to a non-diagonalizable A matrix) and oscillatory modes. The paper suggests a method to find a flexible complexity controlled contractive set

Complexity reduction in motion cueing algorithm for the ULTIMATE driving simulator

The performance of a driving simulator depends on the efficiency of the embedded motion cueing algorithm. An explicit model predictive control was established recently as a pertinent design framework for the motion cueing algorithm. The complexity of the explicit solution increases manifold when the human vestibular model is considered. The present paper focuses on the complexity reduction of explicit solution using low complexity contractive sets for the motion cueing algorithm. The low-complexity explicit controller is formulated for the efficient control of the motion cueing system for the ULTIMATE driving simulator available in Renault

Tuning and tracking the growth of gold nanoparticles synthesized using binary surfactant mixtures

Synthesis of gold nanorods (Au NRs) using surfactant-mediated seeded growth involves the interplay of parameters such as pH, reducing agent, and surfactant among others. The use of binary surfactant mixtures of cetyltrimethylammonium bromide (CTAB) and oleic acid (OA) has been reported by our group previously to obtain other anisotropic shapes. However, there are no reports investigating the growth kinetics and mechanisms of such shapes. Here, we report for the first time a ternary representation for compact visualization of shape transitions of gold nanoparticles (Au NPs) as a function of reaction parameters. Further, using UV-Vis spectrophotometry, the growth kinetics of these shapes was tracked using an in-house developed technique. The interplay between the experimental parameters and the properties of Au NPs was investigated using statistical analysis which showed that the reducing agent and pH were significant in influencing shape and growth kinetics. We further propose a growth mechanism in which the supersaturation of growth units controls the final shapes obtained