18 research outputs found

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

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    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

    Search for gravitational-lensing signatures in the full third observing run of the LIGO-Virgo network

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    Gravitational lensing by massive objects along the line of sight to the source causes distortions of gravitational wave-signals; such distortions may reveal information about fundamental physics, cosmology and astrophysics. In this work, we have extended the search for lensing signatures to all binary black hole events from the third observing run of the LIGO--Virgo network. We search for repeated signals from strong lensing by 1) performing targeted searches for subthreshold signals, 2) calculating the degree of overlap amongst the intrinsic parameters and sky location of pairs of signals, 3) comparing the similarities of the spectrograms amongst pairs of signals, and 4) performing dual-signal Bayesian analysis that takes into account selection effects and astrophysical knowledge. We also search for distortions to the gravitational waveform caused by 1) frequency-independent phase shifts in strongly lensed images, and 2) frequency-dependent modulation of the amplitude and phase due to point masses. None of these searches yields significant evidence for lensing. Finally, we use the non-detection of gravitational-wave lensing to constrain the lensing rate based on the latest merger-rate estimates and the fraction of dark matter composed of compact objects

    Search for eccentric black hole coalescences during the third observing run of LIGO and Virgo

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    Despite the growing number of confident binary black hole coalescences observed through gravitational waves so far, the astrophysical origin of these binaries remains uncertain. Orbital eccentricity is one of the clearest tracers of binary formation channels. Identifying binary eccentricity, however, remains challenging due to the limited availability of gravitational waveforms that include effects of eccentricity. Here, we present observational results for a waveform-independent search sensitive to eccentric black hole coalescences, covering the third observing run (O3) of the LIGO and Virgo detectors. We identified no new high-significance candidates beyond those that were already identified with searches focusing on quasi-circular binaries. We determine the sensitivity of our search to high-mass (total mass M>70 M⊙) binaries covering eccentricities up to 0.3 at 15 Hz orbital frequency, and use this to compare model predictions to search results. Assuming all detections are indeed quasi-circular, for our fiducial population model, we place an upper limit for the merger rate density of high-mass binaries with eccentricities 0<e≤0.3 at 0.33 Gpc−3 yr−1 at 90\% confidence level

    Observation of gravitational waves from the coalescence of a 2.5−4.5 M⊙ compact object and a neutron star

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    Ultralight vector dark matter search using data from the KAGRA O3GK run

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    Among the various candidates for dark matter (DM), ultralight vector DM can be probed by laser interferometric gravitational wave detectors through the measurement of oscillating length changes in the arm cavities. In this context, KAGRA has a unique feature due to differing compositions of its mirrors, enhancing the signal of vector DM in the length change in the auxiliary channels. Here we present the result of a search for U(1)B−L gauge boson DM using the KAGRA data from auxiliary length channels during the first joint observation run together with GEO600. By applying our search pipeline, which takes into account the stochastic nature of ultralight DM, upper bounds on the coupling strength between the U(1)B−L gauge boson and ordinary matter are obtained for a range of DM masses. While our constraints are less stringent than those derived from previous experiments, this study demonstrates the applicability of our method to the lower-mass vector DM search, which is made difficult in this measurement by the short observation time compared to the auto-correlation time scale of DM

    Food-web inferences of stable isotope spatial patterns in copepods and yellowfin tuna in the pelagic eastern Pacific Ocean

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    Evaluating the impacts of climate and fishing on oceanic ecosystems requires an improved understanding of the trophodynamics of pelagic food webs. Our approach was to examine broad-scale spatial relationships among the stable N isotope values of copepods and yellowfin tuna (Thunnus albacares), and to quantify yellowfin tuna trophic status in the food web based on stable-isotope and stomach-contents analyses. Using a generalized additive model fitted to abundance-weighted-average δ15N values of several omnivorous copepod species, we examined isotopic spatial relationships among yellowfin tuna and copepods. We found a broad-scale, uniform gradient in δ15N values of copepods increasing from south to north in a region encompassing the eastern Pacific warm pool and parts of several current systems. Over the same region, a similar trend was observed for the δ15N values in the white muscle of yellowfin tuna caught by the purse-seine fishery, implying limited movement behavior. Assuming the omnivorous copepods represent a proxy for the δ15N values at the base of the food web, the isotopic difference between these two taxa, “ΔYFT-COP,” was interpreted as a trophic-position offset. Yellowfin tuna trophic-position estimates based on their bulk δ15N values were not significantly different than independent estimates based on stomach contents, but are sensitive to errors in the trophic enrichment factor and the trophic position of copepods. An apparent inshore–offshore, east to west gradient in yellowfin tuna trophic position was corroborated using compound-specific isotope analysis of amino acids conducted on a subset of samples. The gradient was not explained by the distribution of yellowfin tuna of different sizes, by seasonal variability at the base of the food web, or by known ambit distances (i.e. movements). Yellowfin tuna stomach contents did not show a regular inshore–offshore gradient in trophic position during 2003–2005, but the trophic-position estimates based on both methods had similar scales of variability. We conclude that trophic status of yellowfin tuna increased significantly from east to west over the study area based on the spatial pattern of ΔYFT-COP values and the difference between the δ15N values of glutamic acid and glycine, “trophic” and “source” amino acids, respectively. These results provide improved depictions of trophic links and biomass flows for food-web models, effective tools to evaluate climate and fishing effects on exploited ecosystems

    Uniform amino acid based trophic positions for lanternfishes and dragonfishes.

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    <p>Relationship between fish length (mm) and amino acid CSIA estimated trophic positions of a) individual lanternfishes, and b) individual dragonfishes from five regions. Also shown is the relationship between individual fish bulk tissue δ<sup>15</sup>N values (‰) and amino acid CSIA estimated trophic positions of c) lanternfishes and d) dragonfishes from five regions. Error bars indicate propagated error from trophic position calculation (see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0050133#s2" target="_blank">methods</a>).</p

    Regional comparison of lanternfish and dragonfish trophic positions estimated by amino acid and bulk tissue isotopic data.

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    #<p>Calculated using Eq. 3.</p><p> (3)*Calculated using Eq. 1 and Eq. 2 as described in “<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0050133#s2" target="_blank">Methods</a>.” Region-specific δ15NPOM and δ15Nzooplankton values from the literature are presented in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0050133#pone.0050133.s005" target="_blank">Table S3</a>.</p><p> (1) (2)</p><p>Summarized values include mean trophic positions (TPs) calculated from bulk tissue δ<sup>15</sup>N values (TP<sub>bulk</sub>) using a trophic enrichment factor (TEF) of 3‰ (mean ± S.D.), and TPs calculated from AA-CSIA data (AA-TP) (mean ± S.D.). Differences in the calculated means between dragonfishes and lanternfishes are shown. Dragonfish values for Hawaii include specimens of both <i>Chauliodus sloani</i> and <i>Idiacanthus fasciola</i>.</p
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