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. Funding Pfizer, Amgen, Merck Sharp & Dohme, Sanofi–Aventis, Daiichi Sankyo, and Regeneron

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

Scattering of Lattice Waves in Planar Surface with Grafted Adatomic Chains

In the present work the scattering properties of a monolayer atomic lattice with grafted adatomic chains are investigated. In the case of two grafted lines, separated by a fixed distance, the localized states induced by the defect are determined. The transmission spectra are also obtained for various distances between the two chains and for additional chains regularly spaced. On the one hand, some Fabry-Perot oscillations are observed; their number is directly related to the number of adatomic lines. On the other hand, Fano resonances due to interaction between the localized states and the continuum are obtained. When the mass value of the adatom decreases, it is shown that the resonances move towards high frequencies in agreement with the harmonic oscillator frequency. Another novelty in this work consists of the observation of zeros of transmission in the spectra

Scattering of Lattice Waves in Planar Surface with Grafted Adatomic Chains

In the present work the scattering properties of a monolayer atomic lattice with grafted adatomic chains are investigated. In the case of two grafted lines, separated by a fixed distance, the localized states induced by the defect are determined. The transmission spectra are also obtained for various distances between the two chains and for additional chains regularly spaced. On the one hand, some Fabry-Perot oscillations are observed; their number is directly related to the number of adatomic lines. On the other hand, Fano resonances due to interaction between the localized states and the continuum are obtained. When the mass value of the adatom decreases, it is shown that the resonances move towards high frequencies in agreement with the harmonic oscillator frequency. Another novelty in this work consists of the observation of zeros of transmission in the spectra

Elastic waves scattering by extended defect surmounting a perfect lattice plane

The matching method is used to analyse the scattering of elastic waves by a structural defect made up several atomic chains surmounting an infinite lattice plane. The vibrational dynamics of the structure is considered within the harmonic approximation framework. The propagating continuum associated to the two vibrational eigenmodes of the perfect lattice is determined and discussed. The localised states induced by the defect are calculated and analysed for heavy and light adatom masses. Their interest appears during the investigation of the diffusion spectra. These localised states allow the interpretation of some observed structures in terms of Fano resonances. It is shown that the resonance number decrease in transmission spectra of light adatom case. The Fano resonances can be absent in the transverse mode, but are always present in the longitudinal one. Their position shifts slightly towards the high frequencies when the number N of perturbating chains increases. When N is higher than the unity, oscillations of Fabry-Perot type appear in the transmission spectra. The number of these oscillations is directly related to the number of adatomic linear chains, in the light and heavy mass cases, in both eigenmodes. We also observe the existence of zeros transmission in the spectra. Because of the large size of the dynamical matrices and complicated graphical resolution spectra, we have limited our study to eight perturbating adatomic linear chains

Orientation effect on the secondary-electron distributions for the HCl double ionization

International audienceMultiple differential cross sections of the double ionization of hydrogen chloride molecule impacted by electrons are here provided within the first Born approximation. The incident and scattered electrons are represented by plane wave functions, whereas the target is described by means of a single-center molecular wave function. The two ejected electrons are modeled by Coulomb wave functions and a Gamow factor is introduced to take into account the Coulomb repulsion between the two outgoing particles. In this work, we study the relative contributions of the four outermost orbitals of the HCl molecule to the double ionization process in the particular case of two electrons ejected from different subshells. The multiple differential cross sections are analyzed for specific target orientations and compared in terms of magnitude and shape. We report a strong dependence of the cross sections versus the target orientation by pointing out the signature of the well-known double ionizing processes, namely, the shake-off and the two-step 1 mechanisms

A free-parameter theoretical model for describing the electron elastic scattering in water in the Geant4 toolkit

The present work provides an accurate description of the elastic scattering process for low-energy electrons (10 eV-10 keV) in liquid water by means of a free-parameter quantum-mechanical treatment. The calculations are performed in the partial-wave formalism by means of a total interaction potential taking into account a static contribution as well as fine effects like exchange and polarization contributions. The obtained results in terms of singly differential and total cross sections exhibit relatively good agreement with available experimental data (in gaseous water). They have been incorporated into the Geant4 toolkit, which has been recently extended with Physics processes for microdosimetry applications in liquid water down to the electronVolt scale. They offer an improved alternative to the semi-empirical and to the screened Rutherford models already available in this very low energy extensio

Optical emissions of products sputtered from Fe, Fe

Powder iron has been bombarded by a 5 keV Kr+ ions in a vacuum better than 10-7 torr and under few 10-6 torr ultra pure oxygen partial pressure. The optical spectra of the sputtered particles were recorded between 340.0 nm and 410.0 nm. These spectra exhibit discrete lines, which are attributed to neutral excited atoms of iron. Two iron oxides, namely hematite (Fe2O$_{3})$ and magnetite (Fe3O$_{4})$, in powder form, were studied under the same experimental conditions and identical lines were observed in the obtained spectra. The absolute intensities of the spectral lines in all spectra were measured and the differences in the recorded yield photons were discussed in term of electron-transfer processes between the excited sputtered atom and the bombarded surface. In accordance with the proposed interpretation, we suggest values for the energy gaps and electronic affinities for the studied oxides and for the oxide layer that might be formed by the adsorption of oxygen atoms