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

Investigation of Self-Compacting Concrete Properties

474 σ.Aντικείμενo της Διδακτορικής Διατριβής είναι η θεωρητική και πειραματική διερεύνηση θεμάτων που αφορούν στο σχεδιασμό των μιγμάτων, στην παρασκευή και στον έλεγχο του νωπού και σκληρυμένου Αυτοσυμπυκνούμενου Σκυροδέματος (ΑΣΣ). Μελετήθηκαν θέματα σύνθεσης και ρεολογίας και η επιρροή μεταβολών στη σύνθεση ΑΣΣ στα μηχανικά χαρακτηριστικά, με έμφαση σε εξειδικευμένα θέματα συνάφειας (φαινόμενο άνω οπλισμών, επιρροή απόστασης ράβδου από το σημείο έγχυσης, σχετικών μετακινήσεων σε νωπό σκυρόδεμα και θέρμανσης σε υψηλές θερμοκρασίες), και σε θέματα ανθεκτικότητας (διαπερατότητα σε νερό και σε χλωριόντα). Επιπλέον, μελετήθηκαν θέματα επαναληψιμότητας των δοκιμών και αναπαραγωγισιμότητας των μιγμάτων. Συγκεκριμένα, μελετήθηκε η συμπεριφορά του ΑΣΣ κατά τη μεταβολή της περιεκτικότητας σε νερό και της χρήσης προσμίκτων (πυριτική παιπάλη, μετακαολίνης) ως υλικών αντικατάστασης του τσιμέντου ή του ασβεστολιθικού φίλερ και τα αποτελέσματα συγκρίθηκαν με την αντίστοιχη συμπεριφορά μιγμάτων Συμβατικού Σκυροδέματος. Κατόπιν εκτεταμένων πειραματικών διερευνήσεων, διατυπώθηκαν αναλυτικές εξισώσεις συσχέτισης των μηχανικών χαρακτηριστικών και των μεγεθών ανθεκτικότητας που εξετάστηκαν με τις μεταβολές στη σύνθεση του ΑΣΣ. Πραγματοποιήθηκε εκτενής συγκριτική αξιολόγηση των αντιπροσωπευτικών τάσεων που χρησιμοποιούνται για την αποτίμηση των ευρημάτων σε θέματα συνάφειας. Προτάθηκε η εφαρμογή μιας νέας μεθόδου εκτίμησης της υδατοπερατότητας, η οποία παρουσιάζει σταθερότητα στα αποτελέσματά της, ενώ επιβεβαιώθηκε πειραματικά η ικανοποιητική επαναληψιμότητα των δοκιμών και η αναπαραγωγισιμότητα μιγμάτων ΑΣΣ.The aim of the Doctoral Thesis is the theoretical and experimental investigation of subjects relating to the mix design, the casting and the testing of fresh and hardened Self-Compacting Concrete (SCC). Subjects relating to composition and rheology, as well as to the effect of SCC composition variation to the mechanical characteristics, emphasising on specialised bond aspects (top-bar effect, effects of rebar distance from casting point, relative displacements in fresh concrete and high temperature treatment), and on durability properties (permeability to water and to chlorides) were investigated. Furthermore, the repeatability of tests and reproducibility of the mixtures were also examined. Specifically, the behaviour of SCC was investigated against variations in the water content and against the use of additives (silica fume, metakaolin) as replacement materials of cement or limestone powder and the results were compared to the corresponding behaviour of Normally Vibrated Concrete. After extensive experimental investigations, analytical functions that correlate the examined mechanical characteristics and durability properties to the variations in SCC composition were formulated. An extensive comparative evaluation of the representative stresses that are used for the assessment of the bond findings was performed. The application of a new methodology of water-permeability estimation, which shows consistency in its results, was suggested, while a satisfactory level of repeatability of the tests and of the reproducibility of SCC mixtures was experimentally confirmed.Ιωάννης Π. Σφήκα

Reproducibility of self-compacting concrete batches between two different EU laboratories

Self Compacting Concrete (SCC) offers a wide variety of advantages during casting. Considering the worldwide uniformity of guidelines concerning the composition and casting instructions for the production of fresh SCC, there is a need to explore the reproducibility of similar self-compacting concrete batches between different countries. In the present study, the fresh properties of similar SCC batches produced in two different laboratories of the European Union are being compared and evaluated

Durability of similar self-compacting concrete batches produced in two different EU laboratories

The present study intends to evaluate the sensitivity of self-compacting concrete (SCC) mixtures, cast in two different laboratories of the European Union, with a focus on rheological parameters, mechanical characteristics and durability properties. Six SCC mixtures with different water-to-binder ratios and silica fume levels of cement replacement and two normally vibrated concrete (NVC) mixtures have been compared. It has been found that the reproducibility of similar mixtures is possible, when using different constituent materials that conform to the European Standards. Comparable rheological, mechanical and durability properties can be achieved. Open porosity and sorptivity appear to be more sensitive than chloride penetrability.Peer reviewe

Enhanced massivity index based on evidence from case studies: towards a robust pre-design assessment of early-age thermal cracking risk and practical recommendations

Tensile stresses resulting from a combination of thermal volumetric changes, due to the heat of hydration and ambient conditions, autogenous deformations and boundary restraints, often induce a significant intrinsic load on massive concrete structures. Whenever such stresses attain the concrete tensile strength, cracking occurs, which may in turn impair the serviceability and durability of the structure. This study is an output of Working Group 7 of RILEM Technical Committee 254-CMS: Thermal cracking in massive concrete structures and is presenting case studies of early-age thermal cracking in massive concrete structures where internal restraining conditions often prevail, such as thick blocks, armour units, footings, dams and spillways, and large-sized columns. It covers the analysis of causes of this type of cracking together with the lessons learned from the collected evidence along with best mitigation practices (often resulting from forensic investigations by means of computer-based simulations). Based on the evidence retrieved from the analysed case studies, the concept of massivity used to indicate potential thermal crack proneness in massive concrete structures is significantly improved to account for binder type and content as well as casting and fresh concrete temperature, in addition to the geometrical characteristics of the element under investigation. The use of such an indicator may lead to a more robust pre-design assessment of the likelihood for thermal cracking occurrence in massive concrete elements, advising designers and contractors dealing with such structures whether more complex analyses should be performed already at the design stage