205 research outputs found

    Broadband Quantum Enhancement of the LIGO Detectors with Frequency-Dependent Squeezing

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    Quantum noise imposes a fundamental limitation on the sensitivity of interferometric gravitational-wave detectors like LIGO, manifesting as shot noise and quantum radiation pressure noise. Here, we present the first realization of frequency-dependent squeezing in full-scale gravitational-wave detectors, resulting in the reduction of both shot noise and quantum radiation pressure noise, with broadband detector enhancement from tens of hertz to several kilohertz. In the LIGO Hanford detector, squeezing reduced the detector noise amplitude by a factor of 1.6 (4.0 dB) near 1 kHz; in the Livingston detector, the noise reduction was a factor of 1.9 (5.8 dB). These improvements directly impact LIGO's scientific output for high-frequency sources (e.g., binary neutron star postmerger physics). The improved low-frequency sensitivity, which boosted the detector range by 15%-18% with respect to no squeezing, corresponds to an increase in the astrophysical detection rate of up to 65%. Frequency-dependent squeezing was enabled by the addition of a 300-meter-long filter cavity to each detector as part of the LIGO A+ upgrade

    De novo variants in the RNU4-2 snRNA cause a frequent neurodevelopmental syndrome

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    Around 60% of individuals with neurodevelopmental disorders (NDD) remain undiagnosed after comprehensive genetic testing, primarily of protein-coding genes1. Large genome-sequenced cohorts are improving our ability to discover new diagnoses in the non-coding genome. Here, we identify the non-coding RNA RNU4-2 as a syndromic NDD gene. RNU4-2 encodes the U4 small nuclear RNA (snRNA), which is a critical component of the U4/U6.U5 tri-snRNP complex of the major spliceosome2. We identify an 18 bp region of RNU4-2 mapping to two structural elements in the U4/U6 snRNA duplex (the T-loop and Stem III) that is severely depleted of variation in the general population, but in which we identify heterozygous variants in 115 individuals with NDD. Most individuals (77.4%) have the same highly recurrent single base insertion (n.64_65insT). In 54 individuals where it could be determined, the de novo variants were all on the maternal allele. We demonstrate that RNU4-2 is highly expressed in the developing human brain, in contrast to RNU4-1 and other U4 homologs. Using RNA-sequencing, we show how 5’ splice site usage is systematically disrupted in individuals with RNU4-2 variants, consistent with the known role of this region during spliceosome activation. Finally, we estimate that variants in this 18 bp region explain 0.4% of individuals with NDD. This work underscores the importance of non-coding genes in rare disorders and will provide a diagnosis to thousands of individuals with NDD worldwide

    Prevalence of Frailty in European Emergency Departments (FEED): an international flash mob study

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    Introduction Current emergency care systems are not optimized to respond to multiple and complex problems associated with frailty. Services may require reconfiguration to effectively deliver comprehensive frailty care, yet its prevalence and variation are poorly understood. This study primarily determined the prevalence of frailty among older people attending emergency care. Methods This cross-sectional study used a flash mob approach to collect observational European emergency care data over a 24-h period (04 July 2023). Sites were identified through the European Task Force for Geriatric Emergency Medicine collaboration and social media. Data were collected for all individuals aged 65 + who attended emergency care, and for all adults aged 18 + at a subset of sites. Variables included demographics, Clinical Frailty Scale (CFS), vital signs, and disposition. European and national frailty prevalence was determined with proportions with each CFS level and with dichotomized CFS 5 + (mild or more severe frailty). Results Sixty-two sites in fourteen European countries recruited five thousand seven hundred eighty-five individuals. 40% of 3479 older people had at least mild frailty, with countries ranging from 26 to 51%. They had median age 77 (IQR, 13) years and 53% were female. Across 22 sites observing all adult attenders, older people living with frailty comprised 14%. Conclusion 40% of older people using European emergency care had CFS 5 + . Frailty prevalence varied widely among European care systems. These differences likely reflected entrance selection and provide windows of opportunity for system configuration and workforce planning

    GW250114: Testing Hawking’s area law and the Kerr nature of black holes

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    The gravitational-wave signal GW250114 was observed by the two LIGO detectors with a network matched-filter signal-to-noise ratio of 80. The signal was emitted by the coalescence of two black holes with near-equal masses m1 ¼ 33.6þ1.2 −0.8M⊙ and m2 ¼ 32.2þ0.8 −1.3M⊙, and small spins χ1;2 ≤ 0.26 (90% credibility) and negligible eccentricity e ≤ 0.03. Postmerger data excluding the peak region are consistent with the dominant quadrupolar ðl ¼ jmj ¼ 2Þ mode of a Kerr black hole and its first overtone. We constrain the modes’ frequencies to 30% of the Kerr spectrum, providing a test of the remnant’s Kerr nature. We also examine Hawking’s area law, also known as the second law of black hole mechanics, which states that the total area of the black hole event horizons cannot decrease with time. A range of analyses that exclude up to five of the strongest merger cycles confirm that the remnant area is larger than the sum of the initial areas to high credibility

    A joint Fermi-GBM and Swift-BAT analysis of gravitational-wave candidates from the third gravitational-wave observing run

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    We present Fermi Gamma-ray Burst Monitor (Fermi-GBM) and Swift Burst Alert Telescope (Swift-BAT) searches for gamma-ray/X-ray counterparts to gravitational-wave (GW) candidate events identified during the third observing run of the Advanced LIGO and Advanced Virgo detectors. Using Fermi-GBM onboard triggers and subthreshold gamma-ray burst (GRB) candidates found in the Fermi-GBM ground analyses, the Targeted Search and the Untargeted Search, we investigate whether there are any coincident GRBs associated with the GWs. We also search the Swift-BAT rate data around the GW times to determine whether a GRB counterpart is present. No counterparts are found. Using both the Fermi-GBM Targeted Search and the Swift-BAT search, we calculate flux upper limits and present joint upper limits on the gamma-ray luminosity of each GW. Given these limits, we constrain theoretical models for the emission of gamma rays from binary black hole mergers

    Global age-sex-specific fertility, mortality, healthy life expectancy (HALE), and population estimates in 204 countries and territories, 1950–2019: a comprehensive demographic analysis for the Global Burden of Disease Study 2019

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    Background: Accurate and up-to-date assessment of demographic metrics is crucial for understanding a wide range of social, economic, and public health issues that affect populations worldwide. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 produced updated and comprehensive demographic assessments of the key indicators of fertility, mortality, migration, and population for 204 countries and territories and selected subnational locations from 1950 to 2019. Methods: 8078 country-years of vital registration and sample registration data, 938 surveys, 349 censuses, and 238 other sources were identified and used to estimate age-specific fertility. Spatiotemporal Gaussian process regression (ST-GPR) was used to generate age-specific fertility rates for 5-year age groups between ages 15 and 49 years. With extensions to age groups 10–14 and 50–54 years, the total fertility rate (TFR) was then aggregated using the estimated age-specific fertility between ages 10 and 54 years. 7417 sources were used for under-5 mortality estimation and 7355 for adult mortality. ST-GPR was used to synthesise data sources after correction for known biases. Adult mortality was measured as the probability of death between ages 15 and 60 years based on vital registration, sample registration, and sibling histories, and was also estimated using ST-GPR. HIV-free life tables were then estimated using estimates of under-5 and adult mortality rates using a relational model life table system created for GBD, which closely tracks observed age-specific mortality rates from complete vital registration when available. Independent estimates of HIV-specific mortality generated by an epidemiological analysis of HIV prevalence surveys and antenatal clinic serosurveillance and other sources were incorporated into the estimates in countries with large epidemics. Annual and single-year age estimates of net migration and population for each country and territory were generated using a Bayesian hierarchical cohort component model that analysed estimated age-specific fertility and mortality rates along with 1250 censuses and 747 population registry years. We classified location-years into seven categories on the basis of the natural rate of increase in population (calculated by subtracting the crude death rate from the crude birth rate) and the net migration rate. We computed healthy life expectancy (HALE) using years lived with disability (YLDs) per capita, life tables, and standard demographic methods. Uncertainty was propagated throughout the demographic estimation process, including fertility, mortality, and population, with 1000 draw-level estimates produced for each metric. Findings: The global TFR decreased from 2•72 (95% uncertainty interval [UI] 2•66–2•79) in 2000 to 2•31 (2•17–2•46) in 2019. Global annual livebirths increased from 134•5 million (131•5–137•8) in 2000 to a peak of 139•6 million (133•0–146•9) in 2016. Global livebirths then declined to 135•3 million (127•2–144•1) in 2019. Of the 204 countries and territories included in this study, in 2019, 102 had a TFR lower than 2•1, which is considered a good approximation of replacement-level fertility. All countries in sub-Saharan Africa had TFRs above replacement level in 2019 and accounted for 27•1% (95% UI 26•4–27•8) of global livebirths. Global life expectancy at birth increased from 67•2 years (95% UI 66•8–67•6) in 2000 to 73•5 years (72•8–74•3) in 2019. The total number of deaths increased from 50•7 million (49•5–51•9) in 2000 to 56•5 million (53•7–59•2) in 2019. Under-5 deaths declined from 9•6 million (9•1–10•3) in 2000 to 5•0 million (4•3–6•0) in 2019. Global population increased by 25•7%, from 6•2 billion (6•0–6•3) in 2000 to 7•7 billion (7•5–8•0) in 2019. In 2019, 34 countries had negative natural rates of increase; in 17 of these, the population declined because immigration was not sufficient to counteract the negative rate of decline. Globally, HALE increased from 58•6 years (56•1–60•8) in 2000 to 63•5 years (60•8–66•1) in 2019. HALE increased in 202 of 204 countries and territories between 2000 and 2019. Interpretation: Over the past 20 years, fertility rates have been dropping steadily and life expectancy has been increasing, with few exceptions. Much of this change follows historical patterns linking social and economic determinants, such as those captured by the GBD Socio-demographic Index, with demographic outcomes. More recently, several countries have experienced a combination of low fertility and stagnating improvement in mortality rates, pushing more populations into the late stages of the demographic transition. Tracking demographic change and the emergence of new patterns will be essential for global health monitoring. Funding: Bill & Melinda Gates Foundation. © 2020 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 licens

    Constraints on the Cosmic Expansion History from GWTC-3

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    This material is based upon work supported by NSFʼs LIGO Laboratory, which is a major facility fully funded by the National Science Foundation. The authors also gratefully acknowledge the support of the Science and Technology Facilities Council (STFC) of the United Kingdom, the Max-Planck-Society (MPS), and the State of Niedersachsen/Germany for support of the construction of Advanced LIGO and construction and operation of the GEO600 detector. Additional support for Advanced LIGO was provided by the Australian Research Council. The authors gratefully acknowledge the Italian Istituto Nazionale di Fisica Nucleare (INFN), the French Centre National de la Recherche Scientifique (CNRS), and the Netherlands Organization for Scientific Research (NWO), for the construction and operation of the Virgo detector and the creation and support of the EGO consortium. The authors also gratefully acknowledge research support from these agencies as well as by the Council of Scientific and Industrial Research of India, the Department of Science and Technology, India, the Science & Engineering Research Board (SERB), India, the Ministry of Human Resource Development, India, the Spanish Agencia Estatal de Investigación (AEI), the Spanish Ministerio de Ciencia e Innovación and Ministerio de Universidades, the Conselleria de Fons Europeus, Universitat i Cultura and the Direcció General de Política Universitaria i Recerca del Govern de les Illes Balears, the Conselleria d’Innovació Universitats, Ciència i Societat Digital de la Generalitat Valenciana and the CERCA Programme Generalitat de Catalunya, Spain, the National Science Centre of Poland and the European Union–European Regional Development Fund, Foundation for Polish Science (FNP), the Swiss National Science Foundation (SNSF), the Russian Foundation for Basic Research, the Russian Science Foundation, the European Commission, the European Social Funds (ESF), the European Regional Develop- ment Funds (ERDF), the Royal Society, the Scottish Funding Council, the Scottish Universities Physics Alliance, the Hungarian Scientific Research Fund (OTKA), the French Lyon Institute of Origins (LIO), the Belgian Fonds de la Recherche Scientifique (FRS-FNRS), Actions de Recherche Concertées (ARC) and Fonds Wetenschappelijk Onderzoek–Vlaanderen (FWO), Bel- gium, the Paris Île-de-France Region, the National Research, Development and Innovation Office Hungary (NKFIH), the National Research Foundation of Korea, the Natural Science and Engineering Research Council Canada, Canadian Foundation for Innovation (CFI), the Brazilian Ministry of Science, Technology, and Innovations, the International Center for Theoretical Physics South American Institute for Fundamental Research (ICTP- SAIFR), the Research Grants Council of Hong Kong, the National Natural Science Foundation of China (NSFC), the Leverhulme Trust, the Research Corporation, the Ministry of Science and Technology (MOST), Taiwan, the United States Department of Energy, and the Kavli Foundation. The authors gratefully acknowledge the support of the NSF, STFC, INFN, and CNRS for provision of computational resources. This work was supported by MEXT, JSPS Leading-edge Research Infrastructure Program, JSPS Grant-in-Aid for Specially Promoted Research 26000005, JSPS Grant-in-Aid for Scientific Research on Innovative Areas 2905: JP17H06358, JP17H06361, and JP17H06364, JSPS Core-to- Core Program A. Advanced Research Networks, JSPS Grant- in-Aid for Scientific Research (S) 17H06133 and 20H05639, JSPS Grant-in-Aid for Transformative Research Areas (A) 20A203: JP20H05854, the joint research program of the Institute for Cosmic Ray Research, University of Tokyo, National Research Foundation (NRF) and Computing Infra- structure Project of KISTI-GSDC in Korea, Academia Sinica (AS), AS Grid Center (ASGC), and the Ministry of Science and Technology (MoST) in Taiwan under grants including AS- CDA-105-M06, Advanced Technology Center (ATC) of NAOJ, Mechanical Engineering Center of KEK. We would like to thank all of the essential workers who put their health at risk during the COVID-19 pandemic, without whom we would not have been able to complete this work.Peer reviewe
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