Correction to: Natural capitals for nature's contributions to people: the case of Japan
In: Sustainability Science
A correction to this paper has been published: https://doi.org/10.1007/s11625-021-00939-6
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In: Sustainability Science
A correction to this paper has been published: https://doi.org/10.1007/s11625-021-00939-6
BACKGROUND: Prognostic value or clinical implications of fluid status monitoring in liver cirrhosis are not fully elucidated. Tolvaptan, an orally available, selective vasopressin V2-receptor antagonist approved for hyponatremia in the United States and European Union. It is also used for cirrhotic ascites at a relatively low dose (3.75 mg to 7.5 mg) in Japan, exerts its diuretic function by excreting electrolyte-free water. We hypothesized that bioimpedance-defined dynamic changes in fluid status allow prediction of response of V2 antagonism and survival in cirrhotic patients. METHODS: In this prospective observational study, 30 patients with decompensated liver cirrhosis who were unresponsive to conventional diuretics were enrolled. Detailed serial changes of body composition that were assessed by using non-invasive bioimpedance analysis (BIA) devices, along with biochemical studies, were monitored at 5 time points. RESULTS: Sixteen patients were classified as short-term responders (53%). Rapid and early decrease of BIA-defined intracellular water, as soon as 6 h after the first dose (ΔICW(BIA)%-6 h), significantly discriminated responders from non-responders (AUC = 0.97, P < 0.0001). ΔICW(BIA)%-6 h was highly correlated with the change of BIA-derived phase angle of trunk, e.g. reduced body reactance operated at 50 kHz after 24 h of the first dose of tolvaptan. Lower baseline blood urea nitrogen and lower serum aldosterone were predictive of a rapid and early decrease of ICW(BIA). A rapid and early decrease of ICW(BIA) in response to tolvaptan was also predictive of a better transplant-free survival. CONCLUSIONS: BIA-defined water compartment monitoring may help predict short-term efficacy and survival in decompensated cirrhotic patients treated with tolvaptan.
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Die Rom I-Verordnung – das neue zentrale Regelwerk Ab dem 17.12.2009 stellt die Rom I-Verordnung das Internationale Vertragsrecht auf eine vollkommen neue Basis. Die Rom I-VO tritt an die Stelle der Art. 27 ff. EGBGB und löst größtenteils auch das Europäische Schuldvertragsübereinkommen von 1980 ab. Auch das Recht der außervertraglichen Schuldverhältnisse erfährt mit der Rom II-Verordnung eine Neuregelung. Vielfältige Internationale Übereinkommen, europäische Verordnungen und Richtlinien sowie ausländische vertrags- und verfahrensrechtliche Bestimmungen stellen die Praxis bei Verträgen mit Auslandsberührung vor zusätzliche Probleme. Der "Reithmann/Martiny" – praktisches Arbeitsbuch und fundiertes Nachschlagewerk In dieser Situation bietet der "Reithmann/Martiny" (mit seinem Autorenteam erstklassiger Experten) sichere Orientierung und praxistaugliche Lösungen durch: Ausführliche Darstellung aller relevanten Vertragstypen des Wirtschaftslebens Berücksichtigung auch der außervertraglichen Schuldverhältnisse Behandlung der Vertretungsmacht von natürlichen und juristischen Personen Gerichtsstands- und Schiedsvereinbarungen Umfassende Auswertung in- und ausländischer Rechtsprechung Alle praxisnahen Vertragstypen mit Auslandsberührung Kaufverträge Rz. 891 Warenkauf Rz. 894 Kauf durch Versteigerungen Rz. 1031 Verträge über Dienstleistungen Rz. 1041 Werk-, Bau-, Anlagen-, Architektenvertrag Rz. 1081 Leasingvertrag Rz. 1111 Darlehen Rz. 1161 Bürgschaft, Garantie, Patronatserklärung Rz. 1181 Bankverträge Rz. 1231 Anleihe Rz. 1351 Makler- und Kommissionsvertrag Rz. 1391 Anwaltsvertrag Rz. 1411 Verträge über unbewegliche Sachen Rz. 1491 Grundstückskauf, Bauträgervertrag Rz. 1501 Grundstücksmiete, Grundstückspacht Rz. 1661 Verträge über Rechte am Geistigen Eigentum Rz. 1771 Lizenzverträge/gewerbliche Schutzrechte Rz. 1831 Urheberrechtsverträge Rz. 1941 Franchiseverträge Rz. 2081 Handelsvertreter- und Vertriebsverträge Rz. 2131 Handelsvertretervertrag Rz. 2161 Vertragshändlervertrag Rz. 2251 Finanzmarktverträge Rz. 2341 Beförderungsverträge Rz. 2571 Einzelne Beförderungsverträge Rz. 2711 Speditionsvertrag Rz. 4071 Verträge mit Verbrauchern Rz. 4141 Verbraucherverträge Rz. 4141 Timesharingvertrag Rz. 4281 Verträge über Unternehmenstransaktionen Rz. 4391 Unternehmenskauf Rz. 4391 Joint Venture Rz. 4561 Versicherungsverträge Rz. 4721 Arbeitsverträge Rz. 4801
In: HELIYON-D-23-15509
SSRN
The European Union's Pediatric Regulation has strengthened the development of medicines for children in Europe through its system of obligations and rewards. However, opportunities remain to further optimize pediatric medicine developments, notably in relation to the implementation of the regulatory framework. This paper therefore describes bottlenecks identified by industry that occur during the medicinal development process, including those relating to the scientific advice process, pediatric investigation plan (PIP) development, compliance checks, and study submissions, and offers some considerations and insights to address these. Considerations, which are workable within the current legislative framework, focus on an integrated scientific discussion, optimization of PIP procedures and compliance checks, and an alignment of study‐reporting requirements.
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In: PNAS nexus, Band 3, Heft 2
ISSN: 2752-6542
Abstract
The small intestine and liver play important role in determining oral drug's fate. Both organs are also interconnected through enterohepatic circulation, which imply there are crosstalk through circulating factors such as signaling molecules or metabolites that may affect drug metabolism. Coculture of hepatocytes and intestinal cells have shown to increase hepatic drug metabolism, yet its crosstalk mechanism is still unclear. In this study, we aim to elucidate such crosstalk by coculturing primary human hepatocytes harvested from chimeric mouse (PXB-cells) and iPSc-derived intestinal cells in a microphysiological systems (MPS). Perfusion and direct oxygenation from the MPS were chosen and confirmed to be suitable features that enhanced PXB-cells albumin secretion, cytochrome P450 (CYP) enzymes activity while also maintaining barrier integrity of iPSc-derived intestine cells. Results from RNA-sequencing showed significant upregulation in gene ontology terms related to fatty acids metabolism in PXB-cells. One of such fatty acids, arachidonic acid, enhanced several CYP enzyme activity in similar manner as coculture. From the current evidences, it is speculated that the release of bile acids from PXB-cells acted as stimuli for iPSc-derived intestine cells to release lipoprotein which was ultimately taken by PXB-cells and enhanced CYP activity.
In: Environmental science and pollution research: ESPR, Band 29, Heft 1, S. 779-789
ISSN: 1614-7499
In: International organization, Band 61, Heft 3, S. 527-569
ISSN: 0020-8183
World Affairs Online
Funding for this study was provided by: CancerResearch UK (C6199/A10417 and C399/A2291),the European Union Seventh Framework Programme(FP7/207-2013) grant 258236 collaborative projectSYSCOL, European Research Council project EVO-CAN, the Dutch Cancer Society, Research FundFlanders (F.W.O.) grant no. G.0827.13, the MedicalResearch Council, the Wellcome Trust and Departmentof Health as part of a Health Innovation ChallengeFund grant (R6-388), the National Institute for HealthResearch (NIHR) Oxford Biomedical Research Cen-tre, Ovarian Cancer Action and core funding to theWellcome Trust Centre for Human Genetics from theWellcome Trust (090532/Z/09/Z). The views expressedare those of the authors and not necessarily those ofthe NHS, the NIHR, the Department of Health or theWellcome Trust.DT is funded by an EPSRC doctoral training grantvia CoMPLEX. MG is funded by a Studentshipfrom the Wellcome Trust. TB is funded by theDutch Cancer Society Young Investigator Grant10418. ADB acknowledges funding from the Well-come Trust (102732/Z/13/Z), Cancer Research UK(C31641/A23923) and the Medical Research Coun-cil (MR/M016587/1). FA is a senior researcher forthe F.W.O. TG is a Cancer Research UK CareerDevelopment Fellow (A19771) and a Wellcome TrustInvestigator (202778/Z/16/Z). DNC is funded by aHealth Foundation/Academy of Medical SciencesClinician Scientist Fellowship.The cost of open access publication was provided bycore funding to the Wellcome Trust Centre for HumanGenetics from the Wellcome Trust (090532/Z/09/Z).
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United States National Science Foundation (NSF) ; Science and Technology Facilities Council (STFC) of the United Kingdom ; Max-Planck-Society (MPS) ; State of Niedersachsen/Germany ; Australian Research Council ; International Science Linkages program of the Commonwealth of Australia ; Council of Scientific and Industrial Research of India ; Department of Science and Technology, India ; Science & Engineering Research Board (SERB), India ; Ministry of Human Resource Development, India ; Spanish Ministerio de Economia y Competitividad ; Conselleria d'Economia i Competitivitat and Conselleria d'Educaci, Cultura i Universitats of the Govern de les Illes Balears ; Foundation for Fundamental Research on Matter - Netherlands Organization for Scientific Research ; Polish Ministry of Science and Higher Education ; FOCUS Programme of Foundation for Polish Science ; European Union ; Royal Society ; Scottish Funding Council ; Scottish Universities Physics Alliance ; National Aeronautics and Space Administration ; Hungarian Scientific Research Fund (OTKA) ; Lyon Institute of Origins (LIO) ; National Research Foundation of Korea ; Industry Canada ; Province of Ontario through the Ministry of Economic Development and Innovation ; National Science and Engineering Research Council Canada ; Brazilian Ministry of Science, Technology, and Innovation ; Carnegie Trust ; Leverhulme Trust ; David and Lucile Packard Foundation ; Research Corporation ; Alfred P. Sloan Foundation ; NSF ; STFC ; MPS ; INFN ; CNRS ; Science and Technology Facilities Council ; Science and Technology Facilities Council: ST/L000938/1 ; Science and Technology Facilities Council: ST/I006285/1 ; Science and Technology Facilities Council: ST/I006269/1 ; Science and Technology Facilities Council: ST/L000946/1 ; Science and Technology Facilities Council: ST/L000962/1 ; Science and Technology Facilities Council: ST/L003465/1 ; Science and Technology Facilities Council: ST/K000845/1 ; Science and Technology Facilities Council: ST/J00166X/1 ; Science and Technology Facilities Council: ST/L000911/1 Gravitational Waves ; Science and Technology Facilities Council: Gravitational Waves ; Science and Technology Facilities Council: PPA/G/S/2002/00652 ; Science and Technology Facilities Council: ST/I006269/1 Gravitational Waves ; Science and Technology Facilities Council: ST/L000911/1 ; Science and Technology Facilities Council: 1362895 ; Science and Technology Facilities Council: ST/I006277/1 ; Science and Technology Facilities Council: ST/H002359/1 ; Science and Technology Facilities Council: ST/K005014/1 ; Science and Technology Facilities Council: ST/K00137X/1 ; Science and Technology Facilities Council: ST/M006735/1 ; Science and Technology Facilities Council: ST/M000931/1 ; Science and Technology Facilities Council: ST/L000938/1 Gravitational Waves ; We describe directed searches for continuous gravitational waves (GWs) in data from the sixth Laser Interferometer Gravitational-wave Observatory (LIGO) science data run. The targets were nine young supernova remnants not associated with pulsars; eight of the remnants are associated with non-pulsing suspected neutron stars. One target ' s parameters are uncertain enough to warrant two searches, for a total of 10. Each search covered a broad band of frequencies and first and second frequency derivatives for a fixed sky direction. The searches coherently integrated data from the two LIGO interferometers over time spans from 5.3-25.3 days using the matched-filtering. -statistic. We found no evidence of GW signals. We set 95% confidence upper limits as strong (low) as 4 x 10(-25) on intrinsic strain, 2 x 10(-7) on fiducial ellipticity, and 4 x 10(-5) on r-mode amplitude. These beat the indirect limits from energy conservation and are within the range of theoretical predictions for neutron-star ellipticities and r-mode amplitudes.
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United States National Science Foundation (NSF) ; Science and Technology Facilities Council (STFC) of the United Kingdom ; Max-Planck-Society (MPS) ; State of Niedersachsen/Germany ; Italian Istituto Nazionale di Fisica Nucleare (INFN) ; French Centre National de la Recherche Scientifique (CNRS) ; Australian Research Council ; International Science Linkages program of the Commonwealth of Australia ; Council of Scientific and Industrial Research of India ; Department of Science and Technology, India ; Science & Engineering Research Board (SERB), India ; Ministry of Human Resource Development, India ; Spanish Ministerio de Economia y Competitividad ; Conselleria d'Economia i Competitivitat and Conselleria d'Educaci, Cultura i Universitats of the Govern de les Illes Balears ; Netherlands Organisation for Scientific Research ; National Science Centre of Poland ; European Union ; Royal Society ; Scottish Funding Council ; Scottish Universities Physics Alliance ; National Aeronautics and Space Administration ; Hungarian Scientific Research Fund (OTKA) ; Lyon Institute of Origins (LIO) ; National Research Foundation of Korea ; Industry Canada ; Province of Ontario through the Ministry of Economic Development and Innovation ; Natural Science and Engineering Research Council, Canada ; Brazilian Ministry of Science, Technology, and Innovation ; Carnegie Trust ; Leverhulme Trust ; David and Lucile Packard Foundation ; Research Corporation ; Alfred P. Sloan Foundation ; NSF ; STFC ; MPS ; INFN ; CNRS ; Science and Technology Facilities Council ; Science and Technology Facilities Council: ST/L000938/1 Gravitational Waves ; Science and Technology Facilities Council: 1362895 ; Science and Technology Facilities Council: ST/L000962/1 ; Science and Technology Facilities Council: ST/I006285/1 Gravitational Waves ; Science and Technology Facilities Council: ST/L003465/1 ; Science and Technology Facilities Council: ST/L000962/1 Gravitational Waves ; Science and Technology Facilities Council: ST/I006285/1 ; Science and Technology Facilities Council: ST/I006242/1 Gravitational Waves ; Science and Technology Facilities Council: ST/J000019/1 ; Science and Technology Facilities Council: ST/N00003X/1 ; Science and Technology Facilities Council: ST/L000946/1 ; Science and Technology Facilities Council: ST/N000064/1 ; Science and Technology Facilities Council: ST/L000954/1 Gravitational Waves ; Science and Technology Facilities Council: ST/K000845/1 ; Science and Technology Facilities Council: ST/I006269/1 ; Science and Technology Facilities Council: ST/L000938/1 ; Science and Technology Facilities Council: Gravitational Waves ; Science and Technology Facilities Council: ST/K005014/1 ; Science and Technology Facilities Council: ST/I006269/1 Gravitational Waves ; We present the results of a search for long-duration gravitational wave transients in two sets of data collected by the LIGO Hanford and LIGO Livingston detectors between November 5, 2005 and September 30, 2007, and July 7, 2009 and October 20, 2010, with a total observational time of 283.0 days and 132.9 days, respectively. The search targets gravitational wave transients of duration 10-500 s in a frequency band of 40-1000 Hz, with minimal assumptions about the signal waveform, polarization, source direction, or time of occurrence. All candidate triggers were consistent with the expected background; as a result we set 90% confidence upper limits on the rate of long-duration gravitational wave transients for different types of gravitational wave signals. For signals from black hole accretion disk instabilities, we set upper limits on the source rate density between 3.4 x 10(-5) and 9.4 x 10(-4) Mpc(-3) yr(-1) at 90% confidence. These are the first results from an all-sky search for unmodeled long-duration transient gravitational waves.
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Advanced LIGO ; Science and Technology Facilities Council (STFC) of the United Kingdom ; Australian Research Council ; Council of Scientific and Industrial Research of India, Department of Science and Technology, India ; Science & Engineering Research Board (SERB), India ; Ministry of Human Resource Development, India ; Spanish Ministerio de Economia y Competitividad ; Conselleria d'Economia i Competitivitat and Conselleria d'Educacio, Cultura i Universitats of the Govern de les Illes Balears ; National Science Centre of Poland ; FOCUS Programme of Foundation for Polish Science ; European Union ; Royal Society ; Scottish Funding Council ; Scottish Universities Physics Alliance ; Lyon Institute of Origins (LIO) ; National Research Foundation of Korea ; Industry Canada ; Province of Ontario through the Ministry of Economic Development and Innovation ; National Science and Engineering Research Council Canada ; Brazilian Ministry of Science, Technology, and Innovation ; Research Corporation, Ministry of Science and Technology (MOST), Taiwan ; Kavli Foundation ; Science and Technology Facilities Council ; Science and Technology Facilities Council: ST/L000954/1 Gravitational Waves ; Science and Technology Facilities Council: ST/L000946/1 ; Science and Technology Facilities Council: ST/I006269/1 Gravitational Waves ; Science and Technology Facilities Council: ST/I006242/1 Gravitational Waves ; Science and Technology Facilities Council: ST/L003465/1 ; Science and Technology Facilities Council: ST/J000019/1 ; Science and Technology Facilities Council: ST/N000072/1 ; Science and Technology Facilities Council: ST/K000845/1 ; Science and Technology Facilities Council: ST/I006269/1 ; Science and Technology Facilities Council: ST/N000633/1 ; Science and Technology Facilities Council: ST/M000931/1 ; Science and Technology Facilities Council: ST/K005014/1 ; Science and Technology Facilities Council: PPA/G/S/2002/00652 ; Science and Technology Facilities Council: Gravitational Waves ; Science and Technology Facilities Council: ST/N00003X/1 ; We present a possible observing scenario for the Advanced LIGO and Advanced Virgo gravitational-wave detectors over the next decade, with the intention of providing information to the astronomy community to facilitate planning for multi-messenger astronomy with gravitational waves. We determine the expected sensitivity of the network to transient gravitational-wave signals, and study the capability of the network to determine the sky location of the source. We report our findings for gravitational-wave transients, with particular focus on gravitational-wave signals from the inspiral of binary neutron-star systems, which are considered the most promising for multi-messenger astronomy. The ability to localize the sources of the detected signals depends on the geographical distribution of the detectors and their relative sensitivity, and 90% credible regions can be as large as thousands of square degrees when only two sensitive detectors are operational. Determining the sky position of a significant fraction of detected signals to areas of 5 deg(2) to 20 deg(2) will require at least three detectors of sensitivity within a factor of similar to 2 of each other and with a broad frequency bandwidth. Should the third LIGO detector be relocated to India as expected, a significant fraction of gravitational-wave signals will be localized to a few square degrees by gravitational-wave observations alone.
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Australian Research Council ; International Science Linkages program of the Commonwealth of Australia ; Council of Scientific and Industrial Research of India, Department of Science and Technology, India ; Science and Engineering Research Board, India ; Ministry of Human Resource Development, India ; Spanish Ministerio de Economia y Competitividad ; Conselleria d'Economia i Competitivitat ; Cultura i Universitats of the Govern de les Illes Balears ; Foundation for Fundamental Research on Matter - Netherlands Organisation for Scientific Research ; National Science Centre of Poland ; European Union ; Royal Society ; Scottish Funding Council ; Scottish Universities Physics Alliance ; National Aeronautics and Space Administration ; Hungarian Scientific Research Fund ; Lyon Institute of Origins ; National Research Foundation of Korea ; Industry Canada ; Province of Ontario through the Ministry of Economic Development and Innovation ; National Science and Engineering Research Council Canada ; Brazilian Ministry of Science, Technology, and Innovation ; Carnegie Trust ; Leverhulme Trust ; David and Lucile Packard Foundation ; Research Corporation ; Alfred P. Sloan Foundation ; Conselleria d'Educacio ; Science and Technology Facilities Council ; Science and Technology Facilities Council: ST/L000962/1 Gravitational Waves ; Science and Technology Facilities Council: 1362895 ; Science and Technology Facilities Council: ST/I006285/1 Gravitational Waves ; Science and Technology Facilities Council: ST/L000938/1 Gravitational Waves ; Science and Technology Facilities Council: ST/L000962/1 ; Science and Technology Facilities Council: ST/K000845/1 ; Science and Technology Facilities Council: Gravitational Waves ; Science and Technology Facilities Council: ST/K005014/1 ; Science and Technology Facilities Council: ST/L003465/1 ; Science and Technology Facilities Council: ST/L000938/1 ; Science and Technology Facilities Council: ST/N000064/1 ; Science and Technology Facilities Council: ST/L000946/1 ; Science and Technology Facilities Council: ST/L000954/1 Gravitational Waves ; Science and Technology Facilities Council: ST/I006269/1 Gravitational Waves ; Science and Technology Facilities Council: ST/I006269/1 ; Science and Technology Facilities Council: ST/J000019/1 ; Science and Technology Facilities Council: ST/I006242/1 Gravitational Waves ; In this paper we present the results of the first low frequency all-sky search of continuous gravitational wave signals conducted on Virgo VSR2 and VSR4 data. The search covered the full sky, a frequency range between 20 and 128 Hz with a range of spin-down between -1.0 x 10(-10) and +1.5 x 10(-11) Hz/s, and was based on a hierarchical approach. The starting point was a set of short fast Fourier transforms, of length 8192 s, built from the calibrated strain data. Aggressive data cleaning, in both the time and frequency domains, has been done in order to remove, as much as possible, the effect of disturbances of instrumental origin. On each data set a number of candidates has been selected, using the Frequency Hough transform in an incoherent step. Only coincident candidates among VSR2 and VSR4 have been examined in order to strongly reduce the false alarm probability, and the most significant candidates have been selected. The criteria we have used for candidate selection and for the coincidence step greatly reduce the harmful effect of large instrumental artifacts. Selected candidates have been subject to a follow-up by constructing a new set of longer fast Fourier transforms followed by a further incoherent analysis, still based on the Frequency Hough transform. No evidence for continuous gravitational wave signals was found, and therefore we have set a population-based joint VSR2-VSR4 90% confidence level upper limit on the dimensionless gravitational wave strain in the frequency range between 20 and 128 Hz. This is the first all-sky search for continuous gravitational waves conducted, on data of ground-based interferometric detectors, at frequencies below 50 Hz. We set upper limits in the range between about 10(-24) and 2 x 10(-23) at most frequencies. Our upper limits on signal strain show an improvement of up to a factor of similar to 2 with respect to the results of previous all-sky searches at frequencies below 80 Hz.
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United States National Science Foundation (NSF) ; Science and Technology Facilities Council (STFC) of the United Kingdom ; MaxPlanck- Society (MPS) ; State of Niedersachsen/Germany ; Australian Research Council ; Netherlands Organisation for Scientific Research ; EGO consortium ; Council of Scientific and Industrial Research of India, Department of Science and Technology, India ; Science AMP; Engineering Research Board (SERB), India ; Ministry of Human Resource Development, India ; Spanish Ministerio de Economia y Competitividad ; Conselleria d'Economia i Competitivitat and Conselleria d'Educacio Cultura i Universitats of the Govern de les Illes Balears ; National Science Centre of Poland ; European Union ; Royal Society ; Scottish Funding Council ; Scottish Universities Physics Alliance ; Lyon Institute of Origins (LIO) ; National Research Foundation of Korea, Industry Canada ; Province of Ontario through the Ministry of Economic Development and Innovation ; National Science and Engineering Research Council Canada ; Brazilian Ministry of Science, Technology, and Innovation ; Leverhulme Trust ; Research Corporation, Ministry of Science and Technology (MOST), Taiwan ; Kavli Foundation ; NSF ; STFC ; MPS ; INFN ; CNRS ; Science and Technology Facilities Council ; State of Niedersachsen/Germany: GEO600 ; Science and Technology Facilities Council: ST/K005014/1 ; Science and Technology Facilities Council: ST/L000938/1 Gravitational Waves ; Science and Technology Facilities Council: ST/N000072/1 ; Science and Technology Facilities Council: PPA/G/S/2002/00652 ; Science and Technology Facilities Council: ST/I006269/1 ; Science and Technology Facilities Council: ST/L000962/1 ; Science and Technology Facilities Council: ST/J00166X/1 ; Science and Technology Facilities Council: ST/M006735/1 ; Science and Technology Facilities Council: ST/I006285/1 Gravitational Waves ; Science and Technology Facilities Council: ST/J000019/1 Gravitational Waves ; Science and Technology Facilities Council: ST/I006285/1 ; Science and Technology Facilities Council: ST/J000019/1 ; Science and Technology Facilities Council: 1362895 ; Science and Technology Facilities Council: ST/M000931/1 ; Science and Technology Facilities Council: ST/L000962/1 Gravitational Waves ; Science and Technology Facilities Council: ST/L000938/1 ; Science and Technology Facilities Council: ST/K000845/1 ; Science and Technology Facilities Council: ST/I006242/1 Gravitational Waves ; Science and Technology Facilities Council: ST/L003465/1 ; Science and Technology Facilities Council: ST/G504284/1 ; Science and Technology Facilities Council: ST/I006269/1 Gravitational Waves ; Science and Technology Facilities Council: ST/L000954/1 Gravitational Waves ; Science and Technology Facilities Council: ST/N00003X/1 ; Science and Technology Facilities Council: Gravitational Waves ; Science and Technology Facilities Council: ST/N000633/1 ; Science and Technology Facilities Council: ST/L000946/1 ; The discovery of the gravitational-wave (GW) source GW150914 with the Advanced LIGO detectors provides the first observational evidence for the existence of binary black hole (BH) systems that inspiral and merge within the age of the universe. Such BH mergers have been predicted in two main types of formation models, involving isolated binaries in galactic fields or dynamical interactions in young and old dense stellar environments. The measured masses robustly demonstrate that relatively heavy BHs (greater than or similar to 25M(circle dot)) can form in nature. This discovery implies relatively weak massive-star winds and thus the formation of GW150914 in an environment with a metallicity lower than about 1/2 of the solar value. The rate of binary-BH (BBH) mergers inferred from the observation of GW150914 is consistent with the higher end of rate predictions (greater than or similar to 1 Gpc(-3) yr(-1)) from both types of formation models. The low measured redshift (z similar or equal to 0.1) of GW150914 and the low inferred metallicity of the stellar progenitor imply either BBH formation in a low-mass galaxy in the local universe and a prompt merger, or formation at high redshift with a time delay between formation and merger of several Gyr. This discovery motivates further studies of binary-BH formation astrophysics. It also has implications for future detections and studies by Advanced LIGO and Advanced Virgo, and GW detectors in space.
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