13 research outputs found
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
Geometry of the décollement below eastern Bangladesh and implications for seismic hazard
Eastern Bangladesh sits on the seismically active Chittagong-Myanmar fold and thrust belt (CMFB), a north-trending accretionary wedge on the eastern side of the India-Eurasia collision. Earthquakes on the basal décollement and associated thrusts within the CMFB present a hazard to this densely populated region. In this study, we interpret 28 seismic reflection profiles from both published and unpublished sources to constrain the depth of the basal décollement. To convert profiles from the time domain to the depth domain, we integrate sonic log and seismic stacking velocity data to generate time-velocity relationships for different parts of the CMFB. Our analysis reveals that the décollement is ∼9 km deep in northeast and southeast Bangladesh, but shallows to ∼5 km in east-central Bangladesh. The décollement has an area of 7.25 × 104 km2 (∼150 × 450 km), making it capable of an Mw 8.5 earthquake. However, the warped geometry of this fault might act as a rupture barrier were a large earthquake to occur on the décollement. Our combined velocity and fault model lay the groundwork for future studies to address seismic segmentation, ground shaking, and rupture modeling in the CMFB. Finally, we use our compiled data set to analyze the evolution of fold kinematics in the CMFB. We observe that folding style and failure mode varies, from mainly ductile deformation in the foreland to mainly brittle in the hinterland. The dual-failure modes within the CMFB support the hypothesis that a region with ductile deformation may still be capable of seismic behavior.Ministry of Education (MOE)Nanyang Technological UniversityNational Research Foundation (NRF)Published versionThis research was supported by the National Research Foundation Singapore under its Singapore NRF Fellowship scheme (NRF award NRF-NRFF2013-06), by the Earth Observato-ry of Singapore (EOS), by the Singapore Ministry of Education (MOE) under the Research Centers of Excellence initia-tive, and by a Nanyang Technological University Startup grant. This is EOS contribution number 255
Structural segmentation controlled the 2015 Mw 7.8 Gorkha earthquake rupture in Nepal
There is increasing evidence that millennial-scale climate variability played an active role on orbital-scale climate changes, but the mechanism for this remains unclear. A 230Th-dated stalagmite δ18O record between 88 and 22 thousand years (ka) ago from Yongxing Cave in central China characterizes changes in Asian monsoon (AM) strength. After removing the 65°N insolation signal from our record, the δ18O residue is strongly anti-phased with Antarctic temperature variability on sub-orbital timescales during the Marine Isotope Stage (MIS) 3. Furthermore, once the ice volume signal from Antarctic ice core records were removed and extrapolated back to the last two glacial-interglacial cycles, we observe a linear relationship for both short- and long-duration events between Asian and Antarctic climate changes. This provides the robust evidence of a link between northern and southern hemisphere climates that operates through changes in atmospheric circulation. We find that the weakest monsoon closely associated with the warmest Antarctic event always occurred during the Terminations. This finding, along with similar shifts in the opal flux record, suggests that millennial-scale events play a key role in driving the deglaciation through positive feedbacks associated with enhanced upwelling and increasing CO2.NRF (Natl Research Foundation, S’pore)MOE (Min. of Education, S’pore)Published versio
The influence of anthropogenic regulation and evaporite dissolution on earthquake-triggered ground failure
Abstract Remote sensing observations of Searles Lake following the 2019 moment magnitude 7.1 Ridgecrest, California, earthquake reveal an area where surface ejecta is arranged in a repeating hexagonal pattern that is collocated with a solution-mining operation. By analyzing geologic and geotechnical data, here we show that the hexagonal surface ejecta is likely not a result of liquefaction. Instead, we propose dissolution cavity collapse (DCC) as an alternative driving mechanism. We support this theory with pre-event Interferometric Synthetic Aperture Radar data, which reveals differential subsidence patterns and the creation of subsurface void space. We also find that DCC is likely triggered at a lower shaking threshold than classical liquefaction. This and other unknown mechanisms can masquerade as liquefaction, introducing bias into liquefaction prediction models that rely on liquefaction inventories. This paper also highlights the opportunities and drawbacks of using remote sensing data to disentangle the complex factors that influence earthquake-triggered ground failure
Metaprofiling of the bacterial community in sorghum silages inoculated with lactic acid bacteria
To characterize the fermentation process and bacterial diversity of sorghum silage inoculated with Lactiplantibacillus plantarum LpAv, Pediococcus pentosaceus PpM and Lacticaseibacillus paracasei LcAv.EEA RafaelaFil: Puntillo, Melisa. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Santa Fe. Instituto de Lactología Industrial (INLAIN); ArgentinaFil: Puntillo, Melisa. Universidad Nacional del Litoral. Facultad de Ingeniería Química. Instituto de Lactologia Industrial (INLAIN); ArgentinaFil: Peralta, Guillermo H. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Santa Fe. Instituto de Lactologia Industrial (INLAIN); ArgentinaFil: Peralta, Guillermo H. Universidad Nacional del Litoral. Facultad de Ingeniería Química. Instituto de Lactologia Industrial (INLAIN); ArgentinaFil: Bürgi, María D. Milagros. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas, Centro Biotecnológico del Litoral; ArgentinaFil: Bürgi, María D. Milagros. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Biotecnológico del Litoral, Santa Fe; ArgentinaFil: Huber, Paula. Universidad Nacional del Litoral. Instituto Nacional de Limnología (INALI). Laboratorio de Plancton; ArgentinaFil: Huber, Paula. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto Nacional de Limnología (INALI). Laboratorio de Plancton; ArgentinaFil: Huber, Paula. Universidade Federal de São Carlos. Departamento de Hydrobiologia. São Carlos; BrasilFil: Gaggiotti, Mónica C. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Rafaela; ArgentinaFil: Gaggiotti, Mónica C. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Investigación de la Cadena Láctea (IDICAL); Argentina.Fil: Gaggiotti, Mónica C. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigación de la Cadena Láctea (IDICAL); Argentina.Fil: Binetti, Ana G. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Santa Fe. Instituto de Lactologia Industrial (INLAIN); ArgentinaFil: Binetti, Ana G. Universidad Nacional del Litoral. Facultad de Ingeniería Química. Instituto de Lactologia Industrial; ArgentinaFil: Vinderola, Celso Gabriel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Santa Fe. Instituto de Lactologia Industrial (INLAIN); ArgentinaFil: Vinderola, Celso Gabriel. Universidad Nacional del Litoral. Facultad de Ingeniería Química. Instituto de Lactologia Industrial (INLAIN); Argentin
The tectopontine projection in the cat: An experimental anatomical study with comments on pathways for teleceptive impulses to the cerebellum
The phenotypic spectrum of organic acidurias and urea cycle disorders Part 1: the initial presentation (vol 38, pg 1041, 2015)
The phenotypic spectrum of organic acidurias and urea cycle disorders. Part 1: the initial presentation.
BACKGROUND: The clinical presentation of patients with organic acidurias (OAD) and urea cycle disorders (UCD) is variable; symptoms are often non-specific. AIMS/METHODS: To improve the knowledge about OAD and UCD the E-IMD consortium established a web-based patient registry. RESULTS: We registered 795 patients with OAD (n = 452) and UCD (n = 343), with ornithine transcarbamylase (OTC) deficiency (n = 196), glutaric aciduria type 1 (GA1; n = 150) and methylmalonic aciduria (MMA; n = 149) being the most frequent diseases. Overall, 548 patients (69 %) were symptomatic. The majority of them (n = 463) presented with acute metabolic crisis during (n = 220) or after the newborn period (n = 243) frequently demonstrating impaired consciousness, vomiting and/or muscular hypotonia. Neonatal onset of symptoms was most frequent in argininosuccinic synthetase and lyase deficiency and carbamylphosphate 1 synthetase deficiency, unexpectedly low in male OTC deficiency, and least frequently in GA1 and female OTC deficiency. For patients with MMA, propionic aciduria (PA) and OTC deficiency (male and female), hyperammonemia was more severe in metabolic crises during than after the newborn period, whereas metabolic acidosis tended to be more severe in MMA and PA patients with late onset of symptoms. Symptomatic patients without metabolic crises (n = 94) often presented with a movement disorder, mental retardation, epilepsy and psychiatric disorders (the latter in UCD only). CONCLUSIONS: The initial presentation varies widely in OAD and UCD patients. This is a challenge for rapid diagnosis and early start of treatment. Patients with a sepsis-like neonatal crisis and those with late-onset of symptoms are both at risk of delayed or missed diagnosis