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142 results on '"SASAKI, Makoto"'

1. Effects of sawtooth heat pulses on edge flows and turbulence in a tokamak plasma

Author: Zhao, Kaijun, Zhao, Kaijun, Nagashima, Yoshihiko, Guo, Zhibin, Diamond, Patrick H, Dong, Jiaqi, Yan, Longwen, Itoh, Kimitaka, Itoh, Sanae-I, Li, Xiaobo, Li, Jiquan, Fujisawa, Akihide, Inagaki, Shigeru, Cheng, Jun, Xu, Jianqiang, Kosuga, Yusuke, Sasaki, Makoto, Wang, Zhengxiong, Zhang, Huaiqiang, Chen, Yuqian, Cao, Xiaogang, Yu, Deliang, Liu, Yi, Song, Xianming, Xia, Fan, Wang, Shuo, Zhao, Kaijun, Zhao, Kaijun, Nagashima, Yoshihiko, Guo, Zhibin, Diamond, Patrick H, Dong, Jiaqi, Yan, Longwen, Itoh, Kimitaka, Itoh, Sanae-I, Li, Xiaobo, Li, Jiquan, Fujisawa, Akihide, Inagaki, Shigeru, Cheng, Jun, Xu, Jianqiang, Kosuga, Yusuke, Sasaki, Makoto, Wang, Zhengxiong, Zhang, Huaiqiang, Chen, Yuqian, Cao, Xiaogang, Yu, Deliang, Liu, Yi, Song, Xianming, Xia, Fan, and Wang, Shuo
Abstract: Enhancements of edge zonal flows, radial electric fields, and turbulence are observed in electron cyclotron resonance heating-heated plasmas (Zhao et al 2013 Nucl. Fusion 53 083011). In this paper, the effects of sawtooth heat pulses on flows and turbulence are presented. These experiments are performed using multiple Langmuir probe arrays in the edge plasmas of the HL-2A tokamak. The edge zonal flows, radial electric fields, and turbulence are all enhanced by sawteeth. Propagation of the zonal flow and turbulence intensities is also observed. The delay time of the maximal intensity of the electric fields, zonal flows, and turbulence with respect to the sawtooth crashes is estimated as ∼1 ms and comparable to that of the sawtooth-triggered intermediate phases. Not only the zonal flows but also the radial electric fields lag behind the turbulence. Furthermore, the intensities of both the zonal flows and electric fields nearly linearly increase/decrease with the increase/decrease of the turbulence intensity. A double-source predator–prey model analysis suggests that a relatively strong turbulence source may contribute to the dominant zonal flow formation during sawtooth cycles.
Published: 2023

2. Efficacy of Quantitative Susceptibility Mapping with Brain Surface Correction and Vein Removal for Detecting Increase Magnetic Susceptibility in Patients with Alzheimer's Disease

Author: Yamaguchi, Akinori, 1000010374232, Kudo, Kohsuke, Sato, Ryota, Kawata, Yasuo, Udo, Niki, Matsushima, Masaaki, Yabe, Ichiro, Sasaki, Makoto, Harada, Masafumi, Matsukawa, Noriyuki, Shirai, Toru, Ochi, Hisaaki, Bito, Yoshitaka, Yamaguchi, Akinori, 1000010374232, Kudo, Kohsuke, Sato, Ryota, Kawata, Yasuo, Udo, Niki, Matsushima, Masaaki, Yabe, Ichiro, Sasaki, Makoto, Harada, Masafumi, Matsukawa, Noriyuki, Shirai, Toru, Ochi, Hisaaki, and Bito, Yoshitaka
Abstract: Purpose: Studies on quantitative susceptibility mapping (QSM) have reported an increase in magnetic susceptibilities in patients with Alzheimer's disease (AD). Despite the pathological importance of the brain surface areas, they are sometimes excluded in QSM analysis. This study aimed to reveal the efficacy of QSMMethods: Thirty-seven AD patients and 37 age- and sex-matched, cognitively normal (CN) subjects were included. A 3D-gradient echo sequence at 3T MRI was used to obtain QSM. QSM images were created with regularization enabled sophisticated harmonic artifact reduction for phase data (RESHARP) and constrained RESHARP with BSC and/or VR. We conducted ROI analysis between AD patients and CN subjects who did or did not undergo BSC and/or VR using a t-test, to compare the susceptibility values after gray matter weighting. Results: The susceptibility values in RESHARP without BSC were significantly larger in AD patients than in CN subjects in one region (precentral gyrus, 8.1 +/- 2.9 vs. 6.5 +/- 2.1 ppb) without VR and one region with VR (precentral gyrus, 7.5 +/- 2.8 vs. 5.9 +/- 2.0 ppb). Three regions in RESHARP with BSC had significantly larger susceptibilities without VR (precentral gyrus, 7.1 +/- 2.0 vs. 5.9 +/- 2.0 ppb; superior medial frontal gyrus, 5.7 +/- 2.6 vs. 4.2 +/- 3.1 ppb; putamen, 47,8 +/- 16.5 vs. 40.0 +/- 15.9 ppb). In contrast, six regions showed significantly larger susceptibilities with VR in AD patients than in CN subjects (precentral gyrus, 6.4 +/- 1.9 vs. 4.9 +/- 2.7 ppb; superior medial frontal gyrus, 5.3 +/- 2.7 vs. 3.7 +/- 3.3 ppb; orbitofrontal cortex, -2.1 +/- 2.7 vs. -3.6 +/- 3.2 ppb; parahippocampal gyrus, 0.1 +/- 3.6 vs. -1.7 +/- 3.7 ppb; putamen, 45.0 +/- 14.9 vs. 37.6 +/- 14.6 ppb; inferior temporal gyrus, -3.4 +/- 1.5 vs. -4.4 +/- 1.5 ppb).Conclusion: RESHARP with BSC and VR showed more regions of increased susceptibility in AD patients than in CN subjects. This study highlights the efficacy of this method in facilitating the dia
Published: 2023

3. The Compton-Pair telescope: A prototype for a next-generation MeV $\gamma$-ray observatory

Author: Valverde, Janeth, Kirschner, Nicholas, Metzler, Zachary, Smith, Lucas D., Cannady, Nicholas, Caputo, Regina, Kierans, Carolyn, Liceaga-Indart, Iker, Moiseev, Alexander, Parker, Lucas, Sasaki, Makoto, Schoenwald, Adam, Shy, Daniel, Wasti, Sambid, Woolf, Richard, Bolotnikov, Aleksey, Carini, Gabriella, Crosier, A. W., Caligure, T., Dellapenna Jr, Alfred, Fried, Jack, Ghosh, P., Griffin, Sean, Grove, J. Eric, Hays, Elizabeth, Herrmann, Sven, Kong, Emily, McEnery, Julie, Mitchell, John, Perkins, Jeremy S., Phlips, Bernard, Sleator, Clio, Wulf, Eric, Zajczyk, Anna, Valverde, Janeth, Kirschner, Nicholas, Metzler, Zachary, Smith, Lucas D., Cannady, Nicholas, Caputo, Regina, Kierans, Carolyn, Liceaga-Indart, Iker, Moiseev, Alexander, Parker, Lucas, Sasaki, Makoto, Schoenwald, Adam, Shy, Daniel, Wasti, Sambid, Woolf, Richard, Bolotnikov, Aleksey, Carini, Gabriella, Crosier, A. W., Caligure, T., Dellapenna Jr, Alfred, Fried, Jack, Ghosh, P., Griffin, Sean, Grove, J. Eric, Hays, Elizabeth, Herrmann, Sven, Kong, Emily, McEnery, Julie, Mitchell, John, Perkins, Jeremy S., Phlips, Bernard, Sleator, Clio, Wulf, Eric, and Zajczyk, Anna
Abstract: The Compton Pair (ComPair) telescope is a prototype that aims to develop the necessary technologies for future medium energy gamma-ray missions and to design, build, and test the prototype in a gamma-ray beam and balloon flight. The ComPair team has built an instrument that consists of 4 detector subsystems: a double-sided silicon strip detector Tracker, a novel high-resolution virtual Frisch-grid cadmium zinc telluride Calorimeter, and a high-energy hodoscopic cesium iodide Calorimeter, all of which are surrounded by a plastic scintillator anti-coincidence detector. These subsystems together detect and characterize photons via Compton scattering and pair production, enable a veto of cosmic rays, and are a proof-of-concept for a space telescope with the same architecture. A future medium-energy gamma-ray mission enabled through ComPair will address many questions posed in the Astro2020 Decadal survey in both the New Messengers and New Physics and the Cosmic Ecosystems themes. In this contribution, we will give an overview of the ComPair project and steps forward to the balloon flight., Comment: Proceedings for the 38th International Cosmic Ray Conference (ICRC2023)
Published: 2023
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4. Efficacy of Quantitative Susceptibility Mapping with Brain Surface Correction and Vein Removal for Detecting Increase Magnetic Susceptibility in Patients with Alzheimer's Disease

Author: Yamaguchi, Akinori, 1000010374232, Kudo, Kohsuke, Sato, Ryota, Kawata, Yasuo, Udo, Niki, Matsushima, Masaaki, Yabe, Ichiro, Sasaki, Makoto, Harada, Masafumi, Matsukawa, Noriyuki, Shirai, Toru, Ochi, Hisaaki, Bito, Yoshitaka, Yamaguchi, Akinori, 1000010374232, Kudo, Kohsuke, Sato, Ryota, Kawata, Yasuo, Udo, Niki, Matsushima, Masaaki, Yabe, Ichiro, Sasaki, Makoto, Harada, Masafumi, Matsukawa, Noriyuki, Shirai, Toru, Ochi, Hisaaki, and Bito, Yoshitaka
Abstract: Purpose: Studies on quantitative susceptibility mapping (QSM) have reported an increase in magnetic susceptibilities in patients with Alzheimer's disease (AD). Despite the pathological importance of the brain surface areas, they are sometimes excluded in QSM analysis. This study aimed to reveal the efficacy of QSMMethods: Thirty-seven AD patients and 37 age- and sex-matched, cognitively normal (CN) subjects were included. A 3D-gradient echo sequence at 3T MRI was used to obtain QSM. QSM images were created with regularization enabled sophisticated harmonic artifact reduction for phase data (RESHARP) and constrained RESHARP with BSC and/or VR. We conducted ROI analysis between AD patients and CN subjects who did or did not undergo BSC and/or VR using a t-test, to compare the susceptibility values after gray matter weighting. Results: The susceptibility values in RESHARP without BSC were significantly larger in AD patients than in CN subjects in one region (precentral gyrus, 8.1 +/- 2.9 vs. 6.5 +/- 2.1 ppb) without VR and one region with VR (precentral gyrus, 7.5 +/- 2.8 vs. 5.9 +/- 2.0 ppb). Three regions in RESHARP with BSC had significantly larger susceptibilities without VR (precentral gyrus, 7.1 +/- 2.0 vs. 5.9 +/- 2.0 ppb; superior medial frontal gyrus, 5.7 +/- 2.6 vs. 4.2 +/- 3.1 ppb; putamen, 47,8 +/- 16.5 vs. 40.0 +/- 15.9 ppb). In contrast, six regions showed significantly larger susceptibilities with VR in AD patients than in CN subjects (precentral gyrus, 6.4 +/- 1.9 vs. 4.9 +/- 2.7 ppb; superior medial frontal gyrus, 5.3 +/- 2.7 vs. 3.7 +/- 3.3 ppb; orbitofrontal cortex, -2.1 +/- 2.7 vs. -3.6 +/- 3.2 ppb; parahippocampal gyrus, 0.1 +/- 3.6 vs. -1.7 +/- 3.7 ppb; putamen, 45.0 +/- 14.9 vs. 37.6 +/- 14.6 ppb; inferior temporal gyrus, -3.4 +/- 1.5 vs. -4.4 +/- 1.5 ppb).Conclusion: RESHARP with BSC and VR showed more regions of increased susceptibility in AD patients than in CN subjects. This study highlights the efficacy of this method in facilitating the dia
Published: 2023

5. Data-driven modal analysis of nonlinear quantities in turbulent plasmas using multi-field singular value decomposition

Author: YATOMI, Go, NAKATA, Motoki, SASAKI, Makoto, YATOMI, Go, NAKATA, Motoki, and SASAKI, Makoto
Abstract: 0000-0001-5695-5699, Nonlinear dynamics in the two-dimensional multi-component plasma turbulence described by the Hasegawa–Wakatani equation is investigated by using a data-driven modal analysis with the singular value decomposition (SVD). The conventional SVD is extended to 'multi-field SVD' which can decompose multiple turbulence fields simultaneously by a single set of orthonormal basis functions without imposing a priori scale separations. Then, in addition to the mode amplitude labeled by the singular value, the information on the phase relations in the nonlinear quantities such as a transport flux or a triad energy transfer is extracted in the mode space. Through applications to the two-dimensional plasma turbulence, it is revealed that the multi-field SVD can extract the dominant spatial structures for the turbulent transport and the nonlinear energy transfer, preserving the multi-scale nature of the original turbulent fields. It is also demonstrated that one can reduce the dimensionality or information using the multi-field SVD through comparisons with the conventional Fourier decomposition.
Published: 2023

6. The Compton-Pair telescope: A prototype for a next-generation MeV $\gamma$-ray observatory

Author: Valverde, Janeth, Kirschner, Nicholas, Metzler, Zachary, Smith, Lucas D., Cannady, Nicholas, Caputo, Regina, Kierans, Carolyn, Liceaga-Indart, Iker, Moiseev, Alexander, Parker, Lucas, Sasaki, Makoto, Schoenwald, Adam, Shy, Daniel, Wasti, Sambid, Woolf, Richard, Bolotnikov, Aleksey, Carini, Gabriella, Crosier, A. W., Caligure, T., Dellapenna Jr, Alfred, Fried, Jack, Ghosh, P., Griffin, Sean, Grove, J. Eric, Hays, Elizabeth, Herrmann, Sven, Kong, Emily, McEnery, Julie, Mitchell, John, Perkins, Jeremy S., Phlips, Bernard, Sleator, Clio, Wulf, Eric, Zajczyk, Anna, Valverde, Janeth, Kirschner, Nicholas, Metzler, Zachary, Smith, Lucas D., Cannady, Nicholas, Caputo, Regina, Kierans, Carolyn, Liceaga-Indart, Iker, Moiseev, Alexander, Parker, Lucas, Sasaki, Makoto, Schoenwald, Adam, Shy, Daniel, Wasti, Sambid, Woolf, Richard, Bolotnikov, Aleksey, Carini, Gabriella, Crosier, A. W., Caligure, T., Dellapenna Jr, Alfred, Fried, Jack, Ghosh, P., Griffin, Sean, Grove, J. Eric, Hays, Elizabeth, Herrmann, Sven, Kong, Emily, McEnery, Julie, Mitchell, John, Perkins, Jeremy S., Phlips, Bernard, Sleator, Clio, Wulf, Eric, and Zajczyk, Anna
Abstract: The Compton Pair (ComPair) telescope is a prototype that aims to develop the necessary technologies for future medium energy gamma-ray missions and to design, build, and test the prototype in a gamma-ray beam and balloon flight. The ComPair team has built an instrument that consists of 4 detector subsystems: a double-sided silicon strip detector Tracker, a novel high-resolution virtual Frisch-grid cadmium zinc telluride Calorimeter, and a high-energy hodoscopic cesium iodide Calorimeter, all of which are surrounded by a plastic scintillator anti-coincidence detector. These subsystems together detect and characterize photons via Compton scattering and pair production, enable a veto of cosmic rays, and are a proof-of-concept for a space telescope with the same architecture. A future medium-energy gamma-ray mission enabled through ComPair will address many questions posed in the Astro2020 Decadal survey in both the New Messengers and New Physics and the Cosmic Ecosystems themes. In this contribution, we will give an overview of the ComPair project and steps forward to the balloon flight., Comment: Proceedings for the 38th International Cosmic Ray Conference (ICRC2023)
Published: 2023
Full Text: View/download PDF

7. The Compton-Pair telescope: A prototype for a next-generation MeV $\gamma$-ray observatory

Author: Valverde, Janeth, Kirschner, Nicholas, Metzler, Zachary, Smith, Lucas D., Cannady, Nicholas, Caputo, Regina, Kierans, Carolyn, Liceaga-Indart, Iker, Moiseev, Alexander, Parker, Lucas, Sasaki, Makoto, Schoenwald, Adam, Shy, Daniel, Wasti, Sambid, Woolf, Richard, Bolotnikov, Aleksey, Carini, Gabriella, Crosier, A. W., Caligure, T., Dellapenna Jr, Alfred, Fried, Jack, Ghosh, P., Griffin, Sean, Grove, J. Eric, Hays, Elizabeth, Herrmann, Sven, Kong, Emily, McEnery, Julie, Mitchell, John, Perkins, Jeremy S., Phlips, Bernard, Sleator, Clio, Wulf, Eric, Zajczyk, Anna, Valverde, Janeth, Kirschner, Nicholas, Metzler, Zachary, Smith, Lucas D., Cannady, Nicholas, Caputo, Regina, Kierans, Carolyn, Liceaga-Indart, Iker, Moiseev, Alexander, Parker, Lucas, Sasaki, Makoto, Schoenwald, Adam, Shy, Daniel, Wasti, Sambid, Woolf, Richard, Bolotnikov, Aleksey, Carini, Gabriella, Crosier, A. W., Caligure, T., Dellapenna Jr, Alfred, Fried, Jack, Ghosh, P., Griffin, Sean, Grove, J. Eric, Hays, Elizabeth, Herrmann, Sven, Kong, Emily, McEnery, Julie, Mitchell, John, Perkins, Jeremy S., Phlips, Bernard, Sleator, Clio, Wulf, Eric, and Zajczyk, Anna
Abstract: The Compton Pair (ComPair) telescope is a prototype that aims to develop the necessary technologies for future medium energy gamma-ray missions and to design, build, and test the prototype in a gamma-ray beam and balloon flight. The ComPair team has built an instrument that consists of 4 detector subsystems: a double-sided silicon strip detector Tracker, a novel high-resolution virtual Frisch-grid cadmium zinc telluride Calorimeter, and a high-energy hodoscopic cesium iodide Calorimeter, all of which are surrounded by a plastic scintillator anti-coincidence detector. These subsystems together detect and characterize photons via Compton scattering and pair production, enable a veto of cosmic rays, and are a proof-of-concept for a space telescope with the same architecture. A future medium-energy gamma-ray mission enabled through ComPair will address many questions posed in the Astro2020 Decadal survey in both the New Messengers and New Physics and the Cosmic Ecosystems themes. In this contribution, we will give an overview of the ComPair project and steps forward to the balloon flight., Comment: Proceedings for the 38th International Cosmic Ray Conference (ICRC2023)
Published: 2023
Full Text: View/download PDF

8. Efficacy of Quantitative Susceptibility Mapping with Brain Surface Correction and Vein Removal for Detecting Increase Magnetic Susceptibility in Patients with Alzheimer's Disease

Author: Yamaguchi, Akinori, Kudo, Kohsuke, Sato, Ryota, Kawata, Yasuo, Udo, Niki, Matsushima, Masaaki, Yabe, Ichiro, Sasaki, Makoto, Harada, Masafumi, Matsukawa, Noriyuki, Shirai, Toru, Ochi, Hisaaki, Bito, Yoshitaka, Yamaguchi, Akinori, Kudo, Kohsuke, Sato, Ryota, Kawata, Yasuo, Udo, Niki, Matsushima, Masaaki, Yabe, Ichiro, Sasaki, Makoto, Harada, Masafumi, Matsukawa, Noriyuki, Shirai, Toru, Ochi, Hisaaki, and Bito, Yoshitaka
Abstract: Purpose: Studies on quantitative susceptibility mapping (QSM) have reported an increase in magnetic susceptibilities in patients with Alzheimer's disease (AD). Despite the pathological importance of the brain surface areas, they are sometimes excluded in QSM analysis. This study aimed to reveal the efficacy of QSMMethods: Thirty-seven AD patients and 37 age- and sex-matched, cognitively normal (CN) subjects were included. A 3D-gradient echo sequence at 3T MRI was used to obtain QSM. QSM images were created with regularization enabled sophisticated harmonic artifact reduction for phase data (RESHARP) and constrained RESHARP with BSC and/or VR. We conducted ROI analysis between AD patients and CN subjects who did or did not undergo BSC and/or VR using a t-test, to compare the susceptibility values after gray matter weighting. Results: The susceptibility values in RESHARP without BSC were significantly larger in AD patients than in CN subjects in one region (precentral gyrus, 8.1 +/- 2.9 vs. 6.5 +/- 2.1 ppb) without VR and one region with VR (precentral gyrus, 7.5 +/- 2.8 vs. 5.9 +/- 2.0 ppb). Three regions in RESHARP with BSC had significantly larger susceptibilities without VR (precentral gyrus, 7.1 +/- 2.0 vs. 5.9 +/- 2.0 ppb; superior medial frontal gyrus, 5.7 +/- 2.6 vs. 4.2 +/- 3.1 ppb; putamen, 47,8 +/- 16.5 vs. 40.0 +/- 15.9 ppb). In contrast, six regions showed significantly larger susceptibilities with VR in AD patients than in CN subjects (precentral gyrus, 6.4 +/- 1.9 vs. 4.9 +/- 2.7 ppb; superior medial frontal gyrus, 5.3 +/- 2.7 vs. 3.7 +/- 3.3 ppb; orbitofrontal cortex, -2.1 +/- 2.7 vs. -3.6 +/- 3.2 ppb; parahippocampal gyrus, 0.1 +/- 3.6 vs. -1.7 +/- 3.7 ppb; putamen, 45.0 +/- 14.9 vs. 37.6 +/- 14.6 ppb; inferior temporal gyrus, -3.4 +/- 1.5 vs. -4.4 +/- 1.5 ppb).Conclusion: RESHARP with BSC and VR showed more regions of increased susceptibility in AD patients than in CN subjects. This study highlights the efficacy of this method in facilitating the dia
Published: 2023

9. Spatiotemporal dynamics of high-wavenumber turbulence in a basic laboratory plasma

Author: Kawachi, Yuichi, Sasaki, Makoto, Kosuga, Yusuke, Terasaka, Kenichiro, Nishizawa, Takashi, Yamada, Takuma, Kasuya, Naohiro, Moon, Chanho, Inagaki, Shigeru, Kawachi, Yuichi, Sasaki, Makoto, Kosuga, Yusuke, Terasaka, Kenichiro, Nishizawa, Takashi, Yamada, Takuma, Kasuya, Naohiro, Moon, Chanho, and Inagaki, Shigeru
Abstract: High-spatial resolution observation of high-wavenumber broadband turbulence is achieved by controlling the magnetic field to be relatively low and measuring with a azimuthally arranged multi-channel Langmuir array in a basic laboratory plasma. The observed turbulence consists of narrowband low-frequency fluctuations and broadband high-frequency turbulent fluctuations. The low-frequency fluctuations have a frequency of about 0.7 times the ion cyclotron frequency and a spatial scale of 1/10 of the ion inertial scale. In comparison, high-frequency fluctuations have a higher frequency than the ion cyclotron frequency and spatial scales of 1/10–1/40 of the ion inertial scale. Two-dimensional correlation analysis evaluates the spatial and temporal correlation lengths and reveals that the high-wavenumber broadband fluctuations have turbulent characteristics. The measurements give us further understanding of small scale turbulence in space and fusion plasmas.
Published: 2022

10. Observation of subcritical geodesic acoustic mode excitation in the large helical device

Author: IDO, Takeshi, ITOH, Kimitaka, LESUR, M., OSAKABE, Masaki, SHIMIZU, Akihiro, OGAWA, Kunihoro, NISHIURA, Masaki, YAMADA, Ichihiro, YASUHARA, Ryo, Kosuga, Yusuke, Sasaki, Makoto, IDA, Katsumi, INAGAKI, Shigeru, ITOH, Sanae -I., the, LHD Experiment Group, IDO, Takeshi, ITOH, Kimitaka, LESUR, M., OSAKABE, Masaki, SHIMIZU, Akihiro, OGAWA, Kunihoro, NISHIURA, Masaki, YAMADA, Ichihiro, YASUHARA, Ryo, Kosuga, Yusuke, Sasaki, Makoto, IDA, Katsumi, INAGAKI, Shigeru, ITOH, Sanae -I., and the, LHD Experiment Group
Abstract: The abrupt and strong excitation of the geodesic acoustic mode (GAM) has been found in the large helical device (LHD), when the frequency of a chirping energetic particle-driven GAM (EGAM) approaches twice that of the GAM frequency. The temporal evolution of the phase relation between the abrupt GAM and the chirping EGAM is common in all events. The result indicates a coupling between the GAM and the EGAM. In addition, the nonlinear evolution of the growth rate of the GAM is observed, and there is a threshold in the amplitude of the GAM for the appearance of nonlinear behavior. A threshold in the amplitude of the EGAM for the abrupt excitation of the GAM is also observed. According to one theory (Lesur et al 2016 Phys. Rev. Lett. 116 015003, Itoh et al 2016 Plasma Phys. Rep. 42 418) the observed abrupt phenomenon can be interpreted as the excitation of the subcritical instability of the GAM. The excitation of a subcritical instability requires a trigger and a seed with sufficient amplitude. The observed threshold in the amplitude of the GAM seems to correspond with the threshold in the seed, and the threshold in the amplitude of the EGAM seems to correspond with the threshold in the magnitude of the trigger. Thus, the observed threshold supports the interpretation that the abrupt phenomenon is the excitation of a subcritical instability of the GAM., source:T. Ido et al 2017 Nucl. Fusion 57 072009, source:https://doi.org/10.1088/1741-4326/aa665a
Published: 2022

11. Nonlinear Excitation of Subcritical Instabilities in a Toroidal Plasma

Author: LESUR, M., ITOH, Kimitaka, IDO, Takeshi, OSAKABE, Masaki, OGAWA, Kunihoro, SHIMIZU, Akihiro, Sasaki, Makoto, IDA, Katsumi, INAGAKI, Shigeru, ITOH, Sanae-I., LESUR, M., ITOH, Kimitaka, IDO, Takeshi, OSAKABE, Masaki, OGAWA, Kunihoro, SHIMIZU, Akihiro, Sasaki, Makoto, IDA, Katsumi, INAGAKI, Shigeru, and ITOH, Sanae-I.
Abstract: In a collisionless plasma, it is known that linearly stable modes can be destabilized (subcritically) by the presence of structures in phase space. However, nonlinear growth requires the presence of a seed structure with a relatively large threshold in amplitude. We demonstrate that, in the presence of another, linearly unstable (supercritical) mode, wave-wave coupling can provide a seed, which is significantly below the threshold, but can still grow by (and only by) the collaboration of fluid and kinetic nonlinearities. By modeling the subcritical mode kinetically, and the impact of the supercritical mode by simple wave-wave coupling equations, it is shown that this new kind of subcritical instability can be triggered, even when the frequency of the supercritical mode is rapidly sweeping. The model is applied to the bursty onset of geodesic acoustic modes in a LHD experiment. The model recovers several key features such as relative amplitude, time scales, and phase relations. It suggests that the strongest bursts are subcritical instabilities, driven by this mechanism of combined fluid and kinetic nonlinearities., source:Nonlinear Excitation of Subcritical Instabilities in a Toroidal Plasma M. Lesur, K. Itoh, T. Ido, M. Osakabe, K. Ogawa, A. Shimizu, M. Sasaki, K. Ida, S. Inagaki, S.-I. Itoh, and the LHD Experiment Group Phys. Rev. Lett. 116, 015003 – Published 8 January 2016, source:https://doi.org/10.1103/PhysRevLett.116.015003
Published: 2022

12. Strong Destabilization of Stable Modes with a Half-Frequency Associated with Chirping Geodesic Acoustic Modes in the Large Helical Device

Author: IDO, Takeshi, OSAKABE, Masaki, LESUR, M., SHIMIZU, Akihiro, OGAWA, Kunihoro, TOI, Kazuo, NISHIURA, Masaki, Kato, S., Sasaki, Makoto, IDA, Katsumi, INAGAKI, Shigeru, ITOH, Sanae -I., the, LHD Experiment Group, IDO, Takeshi, OSAKABE, Masaki, LESUR, M., SHIMIZU, Akihiro, OGAWA, Kunihoro, TOI, Kazuo, NISHIURA, Masaki, Kato, S., Sasaki, Makoto, IDA, Katsumi, INAGAKI, Shigeru, ITOH, Sanae -I., and the, LHD Experiment Group
Abstract: Abrupt and strong excitation of a mode has been observed when the frequency of a chirping energetic-particle driven geodesic acoustic mode (EGAM) reaches twice the geodesic acoustic mode (GAM) frequency. The frequency of the secondary mode is the GAM frequency, which is a half-frequency of the primary EGAM. Based on the analysis of spatial structures, the secondary mode is identified as a GAM. The phase relation between the secondary mode and the primary EGAM is locked, and the evolution of the growth rate of the secondary mode indicates nonlinear excitation. The results suggest that the primary mode (EGAM) contributes to nonlinear destabilization of a subcritical mode., source:Strong Destabilization of Stable Modes with a Half-Frequency Associated with Chirping Geodesic Acoustic Modes in the Large Helical Device T. Ido, K. Itoh, M. Osakabe, M. Lesur, A. Shimizu, K. Ogawa, K. Toi, M. Nishiura, S. Kato, M. Sasaki, K. Ida, S. Inagaki, S.-I. Itoh, and the LHD Experiment Group Phys. Rev. Lett. 116, 015002 – Published 8 January 2016, source:https://doi.org/10.1103/PhysRevLett.116.015002
Published: 2022

13. Stroke genetics informs drug discovery and risk prediction across ancestries

Author: Mishra, Aniket, Malik, Rainer, Hachiya, Tsuyoshi, Jürgenson, Tuuli, Namba, Shinichi, Posner, Daniel C., Kamanu, Frederick K., Koido, Masaru, Le Grand, Quentin, Shi, Mingyang, He, Yunye, Georgakis, Marios K., Caro, Ilana, Krebs, Kristi, Liaw, Yi-Ching, Vaura, Felix C., Lin, Kuang, Slagsvold Winsvold, Bendik, Srinivasasainagendra, Vinodh, Parodi, Livia, Bae, Hee-Joon, Chauhan, Ganesh, Chong, Michael R., Tomppo, Liisa, Akinyemi, Rufus, Roshchupkin, Gennady V., Habib, Naomi, Jee, Yon Ho, Thomassen, Jesper Qvist, Abedi, Vida, Cárcel-Márquez, Jara, Nygaard, Marianne, Leonard, Hampton L., Yang, Chaojie, Yonova-Doing, Ekaterina, Knol, Maria J., Lewis, Adam J., Judy, Renae L., Ago, Tetsuro, Amouyel, Philippe, Armstrong, Nicole D., Bakker, Mark K., Bartz, Traci M., Bennett, David A., Bis, Joshua C., Bordes, Constance, Børte, Sigrid, Cain, Anael, Ridker, Paul M., Cho, Kelly, Chen, Zhengming, Cruchaga, Carlos, Cole, John W., de Jager, Phil L., de Cid, Rafael, Endres, Matthias, Ferreira, Leslie E., Geerlings, Mirjam I., Gasca, Natalie C., Gudnason, Vilmundur, Hata, Jun, He, Jing, Heath, Alicia K., Ho, Yuk-Lam, Havulinna, Aki S., Hopewell, Jemma C., Hyacinth, Hyacinth I., Inouye, Michael, Jacob, Mina A., Jeon, Christina E., Jern, Christina, Kamouchi, Masahiro, Keene, Keith L., Kitazono, Takanari, Kittner, Steven J., Konuma, Takahiro, Kumar, Amit, Lacaze, Paul, Launer, Lenore J., Lee, Keon-Joo, Lepik, Kaido, Li, Jiang, Li, Liming, Manichaikul, Ani, Markus, Hugh S., Marston, Nicholas A., Meitinger, Thomas, Mitchell, Braxton D., Montellano, Felipe A., Morisaki, Takayuki, Mosley, Thomas H., Nalls, Mike A., Nordestgaard, Børge G., O'Donnell, Martin J., Okada, Yukinori, Onland-Moret, N. Charlotte, Ovbiagele, Bruce, Peters, Annette, Psaty, Bruce M., Rich, Stephen S., Rosand, Jonathan, Sabatine, Marc S., Sacco, Ralph L., Saleheen, Danish, Sandset, Else Charlotte, Salomaa, Veikko, Sargurupremraj, Muralidharan, Sasaki, Makoto, Satizabal, Claudia L., Schmidt, Carsten O., Shimizu, Atsushi, Smith, Nicholas L., Sloane, Kelly L., Sutoh, Yoichi, Sun, Yan V., Tanno, Kozo, Tiedt, Steffen, Tatlisumak, Turgut, Torres-Aguila, Nuria P., Tiwari, Hemant K., Trégouët, David-Alexandre, Trompet, Stella, Tuladhar, Anil Man, Tybjærg-Hansen, Anne, van Vugt, Marion, Vibo, Riina, Verma, Shefali S., Wiggins, Kerri L., Wennberg, Patrik, Woo, Daniel, Wilson, Peter W. F., Xu, Huichun, Yang, Qiong, Yoon, Kyungheon, Millwood, Iona Y., Gieger, Christian, Ninomiya, Toshiharu, Grabe, Hans J., Jukema, J. Wouter, Rissanen, Ina L., Strbian, Daniel, Kim, Young Jin, Chen, Pei-Hsin, Mayerhofer, Ernst, Howson, Joanna M. M., Irvin, Marguerite R., Adams, Hieab, Wassertheil-Smoller, Sylvia, Christensen, Kaare, Ikram, Mohammad A., Rundek, Tatjana, Worrall, Bradford B., Lathrop, G. Mark, Riaz, Moeen, Simonsick, Eleanor M., Kõrv, Janika, França, Paulo H. C., Zand, Ramin, Prasad, Kameshwar, Frikke-Schmidt, Ruth, de Leeuw, Frank-Erik, Liman, Thomas, Haeusler, Karl Georg, Ruigrok, Ynte M., Heuschmann, Peter Ulrich, Longstreth, W. T., Jung, Keum Ji, Bastarache, Lisa, Paré, Guillaume, Damrauer, Scott M., Chasman, Daniel I., Rotter, Jerome I., Anderson, Christopher D., Zwart, John-Anker, Niiranen, Teemu J., Fornage, Myriam, Liaw, Yung-Po, Seshadri, Sudha, Fernández-Cadenas, Israel, Walters, Robin G., Ruff, Christian T., Owolabi, Mayowa O., Huffman, Jennifer E., Milani, Lili, Kamatani, Yoichiro, Dichgans, Martin, Debette, Stephanie, Mishra, Aniket, Malik, Rainer, Hachiya, Tsuyoshi, Jürgenson, Tuuli, Namba, Shinichi, Posner, Daniel C., Kamanu, Frederick K., Koido, Masaru, Le Grand, Quentin, Shi, Mingyang, He, Yunye, Georgakis, Marios K., Caro, Ilana, Krebs, Kristi, Liaw, Yi-Ching, Vaura, Felix C., Lin, Kuang, Slagsvold Winsvold, Bendik, Srinivasasainagendra, Vinodh, Parodi, Livia, Bae, Hee-Joon, Chauhan, Ganesh, Chong, Michael R., Tomppo, Liisa, Akinyemi, Rufus, Roshchupkin, Gennady V., Habib, Naomi, Jee, Yon Ho, Thomassen, Jesper Qvist, Abedi, Vida, Cárcel-Márquez, Jara, Nygaard, Marianne, Leonard, Hampton L., Yang, Chaojie, Yonova-Doing, Ekaterina, Knol, Maria J., Lewis, Adam J., Judy, Renae L., Ago, Tetsuro, Amouyel, Philippe, Armstrong, Nicole D., Bakker, Mark K., Bartz, Traci M., Bennett, David A., Bis, Joshua C., Bordes, Constance, Børte, Sigrid, Cain, Anael, Ridker, Paul M., Cho, Kelly, Chen, Zhengming, Cruchaga, Carlos, Cole, John W., de Jager, Phil L., de Cid, Rafael, Endres, Matthias, Ferreira, Leslie E., Geerlings, Mirjam I., Gasca, Natalie C., Gudnason, Vilmundur, Hata, Jun, He, Jing, Heath, Alicia K., Ho, Yuk-Lam, Havulinna, Aki S., Hopewell, Jemma C., Hyacinth, Hyacinth I., Inouye, Michael, Jacob, Mina A., Jeon, Christina E., Jern, Christina, Kamouchi, Masahiro, Keene, Keith L., Kitazono, Takanari, Kittner, Steven J., Konuma, Takahiro, Kumar, Amit, Lacaze, Paul, Launer, Lenore J., Lee, Keon-Joo, Lepik, Kaido, Li, Jiang, Li, Liming, Manichaikul, Ani, Markus, Hugh S., Marston, Nicholas A., Meitinger, Thomas, Mitchell, Braxton D., Montellano, Felipe A., Morisaki, Takayuki, Mosley, Thomas H., Nalls, Mike A., Nordestgaard, Børge G., O'Donnell, Martin J., Okada, Yukinori, Onland-Moret, N. Charlotte, Ovbiagele, Bruce, Peters, Annette, Psaty, Bruce M., Rich, Stephen S., Rosand, Jonathan, Sabatine, Marc S., Sacco, Ralph L., Saleheen, Danish, Sandset, Else Charlotte, Salomaa, Veikko, Sargurupremraj, Muralidharan, Sasaki, Makoto, Satizabal, Claudia L., Schmidt, Carsten O., Shimizu, Atsushi, Smith, Nicholas L., Sloane, Kelly L., Sutoh, Yoichi, Sun, Yan V., Tanno, Kozo, Tiedt, Steffen, Tatlisumak, Turgut, Torres-Aguila, Nuria P., Tiwari, Hemant K., Trégouët, David-Alexandre, Trompet, Stella, Tuladhar, Anil Man, Tybjærg-Hansen, Anne, van Vugt, Marion, Vibo, Riina, Verma, Shefali S., Wiggins, Kerri L., Wennberg, Patrik, Woo, Daniel, Wilson, Peter W. F., Xu, Huichun, Yang, Qiong, Yoon, Kyungheon, Millwood, Iona Y., Gieger, Christian, Ninomiya, Toshiharu, Grabe, Hans J., Jukema, J. Wouter, Rissanen, Ina L., Strbian, Daniel, Kim, Young Jin, Chen, Pei-Hsin, Mayerhofer, Ernst, Howson, Joanna M. M., Irvin, Marguerite R., Adams, Hieab, Wassertheil-Smoller, Sylvia, Christensen, Kaare, Ikram, Mohammad A., Rundek, Tatjana, Worrall, Bradford B., Lathrop, G. Mark, Riaz, Moeen, Simonsick, Eleanor M., Kõrv, Janika, França, Paulo H. C., Zand, Ramin, Prasad, Kameshwar, Frikke-Schmidt, Ruth, de Leeuw, Frank-Erik, Liman, Thomas, Haeusler, Karl Georg, Ruigrok, Ynte M., Heuschmann, Peter Ulrich, Longstreth, W. T., Jung, Keum Ji, Bastarache, Lisa, Paré, Guillaume, Damrauer, Scott M., Chasman, Daniel I., Rotter, Jerome I., Anderson, Christopher D., Zwart, John-Anker, Niiranen, Teemu J., Fornage, Myriam, Liaw, Yung-Po, Seshadri, Sudha, Fernández-Cadenas, Israel, Walters, Robin G., Ruff, Christian T., Owolabi, Mayowa O., Huffman, Jennifer E., Milani, Lili, Kamatani, Yoichiro, Dichgans, Martin, and Debette, Stephanie
Abstract: Previous genome-wide association studies (GWASs) of stroke - the second leading cause of death worldwide - were conducted predominantly in populations of European ancestry1,2. Here, in cross-ancestry GWAS meta-analyses of 110,182 patients who have had a stroke (five ancestries, 33% non-European) and 1,503,898 control individuals, we identify association signals for stroke and its subtypes at 89 (61 new) independent loci: 60 in primary inverse-variance-weighted analyses and 29 in secondary meta-regression and multitrait analyses. On the basis of internal cross-ancestry validation and an independent follow-up in 89,084 additional cases of stroke (30% non-European) and 1,013,843 control individuals, 87% of the primary stroke risk loci and 60% of the secondary stroke risk loci were replicated (P < 0.05). Effect sizes were highly correlated across ancestries. Cross-ancestry fine-mapping, in silico mutagenesis analysis3, and transcriptome-wide and proteome-wide association analyses revealed putative causal genes (such as SH3PXD2A and FURIN) and variants (such as at GRK5 and NOS3). Using a three-pronged approach4, we provide genetic evidence for putative drug effects, highlighting F11, KLKB1, PROC, GP1BA, LAMC2 and VCAM1 as possible targets, with drugs already under investigation for stroke for F11 and PROC. A polygenic score integrating cross-ancestry and ancestry-specific stroke GWASs with vascular-risk factor GWASs (integrative polygenic scores) strongly predicted ischaemic stroke in populations of European, East Asian and African ancestry5. Stroke genetic risk scores were predictive of ischaemic stroke independent of clinical risk factors in 52,600 clinical-trial participants with cardiometabolic disease. Our results provide insights to inform biology, reveal potential drug targets and derive genetic risk prediction tools across ancestries., Publisher correction: Mishra, A., Malik, R., Hachiya, T. et al. Publisher Correction: Stroke genetics informs drug discovery and risk prediction across ancestries. Nature 612, E7 (2022). DOI: 10.1038/s41586-022-05492-5
Published: 2022
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14. Dosimetric advantages of daily adaptive strategy in IMPT for high-risk prostate cancer

Author: Tamura, Hiroshi, Kobashi, Keiji, 1000080463743, Nishioka, Kentaro, Yoshimura, Takaaki, 1000060400678, Hashimoto, Takayuki, Shimizu, Shinichi, 1000010334236, Ito, Yoichi M., Maeda, Yoshikazu, Sasaki, Makoto, Yamamoto, Kazutaka, Tamamura, Hiroyasu, 1000080360915, Aoyama, Hidefumi, 1000020187537, Shirato, Hiroki, Tamura, Hiroshi, Kobashi, Keiji, 1000080463743, Nishioka, Kentaro, Yoshimura, Takaaki, 1000060400678, Hashimoto, Takayuki, Shimizu, Shinichi, 1000010334236, Ito, Yoichi M., Maeda, Yoshikazu, Sasaki, Makoto, Yamamoto, Kazutaka, Tamamura, Hiroyasu, 1000080360915, Aoyama, Hidefumi, 1000020187537, and Shirato, Hiroki
Abstract: Purpose To evaluate the dosimetric advantages of daily adaptive radiotherapy (DART) in intensity-modulated proton therapy (IMPT) for high-risk prostate cancer by comparing estimated doses of the conventional non-adaptive radiotherapy (NART) that irradiates according to an original treatment plan through the entire treatment and the DART that uses an adaptive treatment plan generated by using daily CT images acquired before each treatment. Methods Twenty-three patients with prostate cancer were included. A treatment plan with 63 Gy (relative biological effectiveness (RBE)) in 21 fractions was generated using treatment planning computed tomography (CT) images assuming that all patients had high-risk prostate cancer for which the clinical target volume (CTV) needs to include prostate and the seminal vesicle (SV) in our treatment protocol. Twenty-one adaptive treatment plans for each patient (total 483 data sets) were generated using daily CT images, and dose distributions were calculated. Using a 3 mm set-up uncertainty in the robust optimization, the doses to the CTV, prostate, SV, rectum, and bladder were compared. Results Estimated accumulated doses of NART and DART in the 23 patients were 60.81 +/- 3.47 Gy (RBE) and 63.24 +/- 1.04 Gy (RBE) for CTV D99 (p < 0.01), 62.99 +/- 1.28 Gy (RBE) and 63.43 +/- 1.33 Gy (RBE) for the prostate D99 (p = 0.2529), and 59.07 +/- 5.19 Gy (RBE) and 63.17 +/- 1.04 Gy (RBE) for SV D99 (p < 0.001). No significant differences were observed between NART and DART in the estimated accumulated dose for the rectum and bladder. Conclusion Compared with the NART, DART was shown to be a useful approach that can maintain the dose coverage to the target without increasing the dose to the organs at risk (OAR) using the 3 mm set-up uncertainty in the robust optimization in patients with high-risk prostate cancer.
Published: 2022

15. Turbulence Simulation on Zonal Flow Formations in the Presence of Parallel Flows

Author: SASAKI, Makoto, KASUYA, Naohiro, KOSUGA, Yusuke, KOBAYASHI, Tatsuya, YAMADA, Takuma, ARAKAWA, Hiroyuki, INAGAKI, Shigeru, ITOH, Kimitaka, SASAKI, Makoto, KASUYA, Naohiro, KOSUGA, Yusuke, KOBAYASHI, Tatsuya, YAMADA, Takuma, ARAKAWA, Hiroyuki, INAGAKI, Shigeru, and ITOH, Kimitaka
Abstract: It is demonstrated that the zonal flow is controlled by the parallel flow in the cylindrical plasmas. A three-dimensional turbulence simulation is performed, based on the reduced fluid model. The background parallel flow is applied by introducing the time independent parallel momentum source. Changing the magnitude of the momentum source, the behavior of the zonal flow is investigated. The drift wave turbulence is affected by the parallel flow, and it shows the spatial competition between turbulence modes. The spatial competition appears/disappears abruptly, depending on the intensity of the parallel momentum source. As a consequence of the transition between the turbulence state, the radial profile of the turbulence drastically changes, which leads to the change of the turbulence force to drive the zonal flow. In this way, the parallel flow indirectly affects the zonal flow through the deformation of the turbulence., source:https://doi.org/10.1585/pfr.14.1401161
Published: 2022

16. Evaluation of Measurement Signal of Heavy Ion Beam Probe of Energetic-Particle Driven Geodesic Acoustic Modes

Author: SASAKI, Makoto, ITOH, Kimitaka, IDO, Takeshi, SHIMIZU, Akihiro, KOBAYASHI, Tatsuya, ARAKAWA, Hiroyuki, KASUYA, Naohiro, FUJISAWA, Akihide, ITOH, Sanae -I., SASAKI, Makoto, ITOH, Kimitaka, IDO, Takeshi, SHIMIZU, Akihiro, KOBAYASHI, Tatsuya, ARAKAWA, Hiroyuki, KASUYA, Naohiro, FUJISAWA, Akihide, and ITOH, Sanae -I.
Abstract: In order to observe spatial profiles of energetic particle driven modes, measurement signal of Heavy Ion Beam Probe (HIBP) is formulated theoretically, focusing on effects of the fast ion density fluctuation and attenuation of the injected beam (line-integral effect). Obtained formula is applied to the density fluctuation measurement of energetic-particle driven geodesic acoustic modes (EGAMs). Intensity of the fluctuation obtained by the HIBP can be up-down asymmetric in the poloidal cross-section due to the effect of the fast ion density fluctuation, when the electron loss cross-section of HIBP due to fast ions is comparable to that due to electrons. A possibility to measure the fast ion density by HIBP is discussed, and the experimental guideline for the specification of the resonance which drives the EGAM is presented., source:https://doi.org/10.1585/pfr.13.3403040
Published: 2022

17. Phenomenological Classification of Turbulence States in Linear Magnetized Plasma PANTA

Author: KOBAYASHI, Tatsuya, INAGAKI, Shigeru, SASAKI, Makoto, KOSUGA, Yusuke, ARAKAWA, Hiroyuki, KIN, Fumiyoshi, YAMADA, Takuma, NAGASHIMA, Yoshihiko, KASUYA, Naohiro, FUJISAWA, Akihide, ITOH, Sanae-I., ITOH, Kimitaka, KOBAYASHI, Tatsuya, INAGAKI, Shigeru, SASAKI, Makoto, KOSUGA, Yusuke, ARAKAWA, Hiroyuki, KIN, Fumiyoshi, YAMADA, Takuma, NAGASHIMA, Yoshihiko, KASUYA, Naohiro, FUJISAWA, Akihide, ITOH, Sanae-I., and ITOH, Kimitaka
Abstract: Changing the experimental conditions such as the neutral pressure and the magnetic field strength provides a drastic change in the turbulence states in linear magnetized helicon plasmas. In order to define the turbulence states and their occurrence region a throughout parameter scan in the two-dimensional parameter space was performed. The classification of the turbulence states is carried out phenomenologically based on the turbulence spectrum and the waveform., source:https://doi.org/10.1585/pfr.12.1401019, identifier:0000-0001-5669-1937
Published: 2022

18. Multiple-Instabilities in Magnetized Plasmas with Density Gradient and Velocity Shears

Author: SASAKI, Makoto, KASUYA, Naohiro, TODA, Shinichiro, YAMADA, Takuma, KOSUGA, Yusuke, ARAKAWA, Hiroyuki, KOBAYASHI, Tatsuya, INAGAKI, Shigeru, FUJISAWA, Akihide, NAGASHIMA, Yoshihiko, ITOH, Kimitaka, ITOH, Sanae-I., SASAKI, Makoto, KASUYA, Naohiro, TODA, Shinichiro, YAMADA, Takuma, KOSUGA, Yusuke, ARAKAWA, Hiroyuki, KOBAYASHI, Tatsuya, INAGAKI, Shigeru, FUJISAWA, Akihide, NAGASHIMA, Yoshihiko, ITOH, Kimitaka, and ITOH, Sanae-I.
Abstract: Multiple free energy sources for instabilities coexist in magnetized plasmas with density gradient and velocity shear. Linear stabilities are investigated, and the mutual relation between resistive drift wave, D'Angelo mode and flute mode is systematically clarified. By evaluating the linear growth rates, dominant instability is categorized in a parameter space. The parallel wavenumber spectrum could be used as a guideline for the identification of the instabilities., source:https://doi.org/10.1585/pfr.12.1401042
Published: 2022

19. Identification of Quasi-Periodic Nonlinear Waveforms in Turbulent Plasmas

Author: INAGAKI, Shigeru, MIWA, Yudai, KOBAYASHI, Tatsuya, YAMADA, Takuma, NAGASHIMA, Yoshihiko, MITSUZONO, Tomohiro, FUJINO, Hiromitsu, SASAKI, Makoto, KASUYA, Naohiro, LESUR, Maxime, KOSUGA, Yusuke, FUJISAWA, Akihide, ITOH, Sanae -I., ITOH, Kimitaka, INAGAKI, Shigeru, MIWA, Yudai, KOBAYASHI, Tatsuya, YAMADA, Takuma, NAGASHIMA, Yoshihiko, MITSUZONO, Tomohiro, FUJINO, Hiromitsu, SASAKI, Makoto, KASUYA, Naohiro, LESUR, Maxime, KOSUGA, Yusuke, FUJISAWA, Akihide, ITOH, Sanae -I., and ITOH, Kimitaka
Abstract: A new method is presented for identifying waveforms of fluctuations in turbulent plasmas. The method is based on heartbeat analysis in which the convolution of a waveform is obtained by employing the phase tracking method. Phase tracking is performed by correlating raw time-series data with a template waveform; the template is evaluated through iteration procedure. The method is applied to fluctuations in a PANTA plasma, and the nonlinear waveform and its distribution of periods are obtained., source:https://doi.org/10.1585/pfr.9.1201016
Published: 2022

20. Measurement of Dynamical Density Profiles Using a Microwave Frequency Comb Reflectometer

Author: INAGAKI, Shigeru, ITOH, Kimitaka, YAMADA, Takuma, ITOH, Sanae -I., TOKUZAWA, Tokihiko, FUJISAWA, Akihide, KASUYA, Naohiro, SASAKI, Makoto, NAGASHIMA, Yoshihiko, ARAKAWA, Hiroyuki, INAGAKI, Shigeru, ITOH, Kimitaka, YAMADA, Takuma, ITOH, Sanae -I., TOKUZAWA, Tokihiko, FUJISAWA, Akihide, KASUYA, Naohiro, SASAKI, Makoto, NAGASHIMA, Yoshihiko, and ARAKAWA, Hiroyuki
Abstract: We propose the use of a microwave comb for measuring the density profile as a continuous function of radius with high temporal resolution. The analysis focuses on phase-sensitive convolution of the reflected waves: convolution of pulses can eliminate statistical noise. The time resolution for constructing the density profile is also discussed., source:https://doi.org/10.1585/pfr.8.1201171
Published: 2022

21. Evaluation of Excitation Conditions of ITG Modes in the PANTA

Author: MIWA, Yudai, KASUYA, Naohiro, SASAKI, Makoto, INAGAKI, Shigeru, ITOH, Kimitaka, YAGI, Masatoshi, FUJISAWA, Akihide, NAGASHIMA, Yoshihiko, LESUR, Maxime, KOBAYASHI, Tatsuya, YAMADA, Soutarou, YAMASHITA, Tetsuo, OTSUBO, Satoshi, KAKIGAWA, Shinsuke, MITSUZONO, Tomohiro, FUJINO, Hirofumi, ITOH, Sanae-I., MIWA, Yudai, KASUYA, Naohiro, SASAKI, Makoto, INAGAKI, Shigeru, ITOH, Kimitaka, YAGI, Masatoshi, FUJISAWA, Akihide, NAGASHIMA, Yoshihiko, LESUR, Maxime, KOBAYASHI, Tatsuya, YAMADA, Soutarou, YAMASHITA, Tetsuo, OTSUBO, Satoshi, KAKIGAWA, Shinsuke, MITSUZONO, Tomohiro, FUJINO, Hirofumi, and ITOH, Sanae-I.
Abstract: To study the nonlinear saturation mechanism in turbulent plasmas, we plan to obseve ion temperature gradient (ITG) modes in the Plasma Assembly for Nonlinear Turbulence Analysis (PANTA). Linear growth rates of ITG modes in the linear device are analyzed to determine their excitation conditions using a three-field fluid model to describe the ion motion. Parameter scans of the linear growth rate show the threshold for ITG mode excitation, and the typical plasma parameters of the PANTA are found in the unstable domain., source:https://doi.org/10.1585/pfr.8.2403133
Published: 2022

22. Evaluation of Spatial Variation of Nonlinear Energy Transfer by Use of Turbulence Diagnostic Simulator

Author: KASUYA, Naohiro, SUGITA, Satoru, SASAKI, Makoto, INAGAKI, Shigeru, YAGI, Masatoshi, ITOH, Kimitaka, ITOH, Sanae-I., KASUYA, Naohiro, SUGITA, Satoru, SASAKI, Makoto, INAGAKI, Shigeru, YAGI, Masatoshi, ITOH, Kimitaka, and ITOH, Sanae-I.
Abstract: Turbulence Diagnostic Simulator is an assembly of simulation codes to clarify the formation mechanism of turbulent structures by numerical diagnostics in magnetically confined plasmas. Global simulations are carried out using a reduced MHD model of drift-interchange mode in helical plasmas, and time series data of 3-D fluctuation fields are produced. It includes localized modes in their rational surfaces, and broad modes spread in the radial direction. Magnitudes of nonlinear couplings from the convective derivative are evaluated in the nonlinear saturated states. The radial profile shows that there exist strong mode excitation near the center, various modes and nonlinear couplings with higher m modes in the middle radius, small number of propagating modes near the edge, which contribute to the pressure profile modification. For the detection of the different features, combination of several diagnostics is necessary., source:https://doi.org/10.1585/pfr.8.2403070, identifier:0000-0001-8210-5700
Published: 2022

23. Statistical Analyses of Turbulent Particle and Momentum Fluxes in a Cylindrical Magnetized Plasma

Author: SASAKI, Makoto, KASUYA, Naohiro, YAGI, Masatoshi, ITOH, Kimitaka, NAGASHIMA, Yoshihiko, INAGAKI, Shigeru, ITOH, Sanae -I., SASAKI, Makoto, KASUYA, Naohiro, YAGI, Masatoshi, ITOH, Kimitaka, NAGASHIMA, Yoshihiko, INAGAKI, Shigeru, and ITOH, Sanae -I.
Abstract: A nonlinear simulation of resistive drift wave turbulence in a cylindrical plasma is carried out. Long time evolution of turbulence with formation of a zonal flow is obtained for more than 1000 times of the typical drift wave period, which is sufficient for statistical analyses. Dynamical particle and momentum balance for the formation of the mean reveals that the radial turbulent fluxes are dominant contributors for the evolution of fluctuations. The particle flux is found to precede the momentum flux for 0.4 times of the typical drift wave period with large temporal variance. The analyses of the time series data of 3-D fields give the understanding of the dynamical structural formation mechanism., source:https://doi.org/10.1585/pfr.8.2401113, identifier:0000-0001-6835-1569
Published: 2022

24. On a Nonlinear Dispersion Effect of Geodesic Acoustic Modes

Author: SASAKI, Makoto, ITOH, Kimitaka, KASUYA, Naohiro, HALLATSCHEK, Klaus, ITOH, Sanae-I., SASAKI, Makoto, ITOH, Kimitaka, KASUYA, Naohiro, HALLATSCHEK, Klaus, and ITOH, Sanae-I.
Abstract: The nonlinear dispersion relation of the geodesic acoustic modes (GAMs) is investigated for tokamaks with a high safety factor and low magnetic shear. We focus on the Reynolds stress as a nonlinearity, which is truncated at the third order of the GAM amplitude. The real frequency of the GAM is modified according to the phase of the nonlinear force acting on the GAM, which depends on the turbulence decorrelation rate. The nonlinear frequency shift is much larger than that from the finite gyro-radius effects in the linear theory, when the poloidal turbulent E × B velocities are comparable to the diamagnetic drift velocity. Under such circumstances, the group velocity is strongly enhanced and becomes comparable with the radial phase velocity. In addition, the magnitude of the nonlinear effects is also evaluated using experimental parameters., source:https://doi.org/10.1585/pfr.8.1403010, identifier:0000-0002-7696-6405
Published: 2022

25. Characterization of isotope effect on ion internal transport barrier and its parameter dependence in the Large Helical Device

Author: KOBAYASHI, Tatsuya, TAKAHASHI, Hiromi, NAGAOKA, Kenichi, TANAKA, Kenji, SEKI, Ryosuke, HAMAGUCHI, Hiroyuki, NAKATA, Motoki, SASAKI, Makoto, YOSHINUMA, Mikiro, IDA, Katsumi, KOBAYASHI, Tatsuya, TAKAHASHI, Hiromi, NAGAOKA, Kenichi, TANAKA, Kenji, SEKI, Ryosuke, HAMAGUCHI, Hiroyuki, NAKATA, Motoki, SASAKI, Makoto, YOSHINUMA, Mikiro, and IDA, Katsumi
Abstract: In this paper, the background physics of the isotope effects in the ion internal transport barrier (ITB) are discussed in detail. An heuristic criterion for the ITB strength is defined based on the nonlinear dependence of the ion thermal diffusivity on the local ion temperature in the L-mode phase. Comparing deuterium plasmas and hydrogen plasmas, two isotope effects on the ion ITB are clarified: stronger ITBs formed in the deuterium plasmas and an ITB concomitant edge confinement degradation in the hydrogen plasmas. Principal component analysis reveals that the ion ITB becomes strong when a high input power normalized by the line averaged electron density is applied and electron density profile is peaked. A gyrokinetic simulation suggests that the ITB profile is determined by the ion temperature gradient driven turbulence, while the way the profile saturates in L-mode plasmas is unknown. In the electron density turbulence behavior, a branch transition is observed, where the increasing trend in turbulence amplitude against the ITB strength is flipped to a decreasing trend across the ITB formation. The radial electric field structure is measured by the charge exchange recombination spectroscopy system. It is found that the radial electric field shear plays a minor role in determining the ITB strength., source:T. Kobayashi et al 2021 Nucl. Fusion 61 126013, source:https://doi.org/10.1088/1741-4326/ac298f, identifier:0000-0001-5669-1937
Published: 2022

26. Behavior of geodesic acoustic mode and limit-cycle oscillation approaching L-H transition in JFT-2M tokamak

Author: KOBAYASHI, Tatsuya, SASAKI, Makoto, IDO, Takeshi, KAMIYA, Kensaku, MIURA, Y, IDA, Katsumi, ITOH, Kimitaka, KOBAYASHI, Tatsuya, SASAKI, Makoto, IDO, Takeshi, KAMIYA, Kensaku, MIURA, Y, IDA, Katsumi, and ITOH, Kimitaka
Abstract: In this paper, a phenomenology of competing behavior between the geodesic acoustic mode (GAM) and the limit-cycle oscillation (LCO) is presented. Before the LCO occurs, the GAM can grow to the observable amplitude via the turbulent Reynolds stress force. Approaching the L-H transition, the LCO is excited and the GAM decays. In the LCO phase, the GAM driving force is possibly suppressed by the nonlocal turbulence amplitude modulation by the LCO., source:T Kobayashi et al 2022 Plasma Phys. Control. Fusion 64 114002, source:https://doi.org/10.1088/1361-6587/ac9333, identifier:0000-0001-5669-1937
Published: 2022

27. Spatiotemporal dynamics of high-wavenumber turbulence in a basic laboratory plasma

Author: KAWACHI, Yuichi, SASAKI, Makoto, KOSUGA, Yusuke, TERASAKA, Kenichiro, NISHIZAWA, Takashi, YAMADA, Takuma, KASUYA, Naohiro, MOON, Chanho, INAGAKI, Shigeru, KAWACHI, Yuichi, SASAKI, Makoto, KOSUGA, Yusuke, TERASAKA, Kenichiro, NISHIZAWA, Takashi, YAMADA, Takuma, KASUYA, Naohiro, MOON, Chanho, and INAGAKI, Shigeru
Abstract: High-spatial resolution observation of high-wavenumber broadband turbulence is achieved by controlling the magnetic field to be relatively low and measuring with a azimuthally arranged multi-channel Langmuir array in a basic laboratory plasma. The observed turbulence consists of narrowband low-frequency fluctuations and broadband high-frequency turbulent fluctuations. The low-frequency fluctuations have a frequency of about 0.7 times the ion cyclotron frequency and a spatial scale of 1/10 of the ion inertial scale. In comparison, high-frequency fluctuations have a higher frequency than the ion cyclotron frequency and spatial scales of 1/10–1/40 of the ion inertial scale. Two-dimensional correlation analysis evaluates the spatial and temporal correlation lengths and reveals that the high-wavenumber broadband fluctuations have turbulent characteristics. The measurements give us further understanding of small scale turbulence in space and fusion plasmas., source:Kawachi, Y., Sasaki, M., Kosuga, Y. et al. Spatiotemporal dynamics of high-wavenumber turbulence in a basic laboratory plasma. Sci Rep 12, 19799 (2022). https://doi.org/10.1038/s41598-022-23559-1, source:https://doi.org/10.1038/s41598-022-23559-1, identifier:0000-0002-5222-6082
Published: 2022

28. Stroke genetics informs drug discovery and risk prediction across ancestries

Author: Mishra, Aniket, Malik, Rainer, Hachiya, Tsuyoshi, Jürgenson, Tuuli, Namba, Shinichi, Posner, Daniel C., Kamanu, Frederick K., Koido, Masaru, Le Grand, Quentin, Shi, Mingyang, He, Yunye, Georgakis, Marios K., Caro, Ilana, Krebs, Kristi, Liaw, Yi-Ching, Vaura, Felix C., Lin, Kuang, Slagsvold Winsvold, Bendik, Srinivasasainagendra, Vinodh, Parodi, Livia, Bae, Hee-Joon, Chauhan, Ganesh, Chong, Michael R., Tomppo, Liisa, Akinyemi, Rufus, Roshchupkin, Gennady V., Habib, Naomi, Jee, Yon Ho, Thomassen, Jesper Qvist, Abedi, Vida, Cárcel-Márquez, Jara, Nygaard, Marianne, Leonard, Hampton L., Yang, Chaojie, Yonova-Doing, Ekaterina, Knol, Maria J., Lewis, Adam J., Judy, Renae L., Ago, Tetsuro, Amouyel, Philippe, Armstrong, Nicole D., Bakker, Mark K., Bartz, Traci M., Bennett, David A., Bis, Joshua C., Bordes, Constance, Børte, Sigrid, Cain, Anael, Ridker, Paul M., Cho, Kelly, Chen, Zhengming, Cruchaga, Carlos, Cole, John W., de Jager, Phil L., de Cid, Rafael, Endres, Matthias, Ferreira, Leslie E., Geerlings, Mirjam I., Gasca, Natalie C., Gudnason, Vilmundur, Hata, Jun, He, Jing, Heath, Alicia K., Ho, Yuk-Lam, Havulinna, Aki S., Hopewell, Jemma C., Hyacinth, Hyacinth I., Inouye, Michael, Jacob, Mina A., Jeon, Christina E., Jern, Christina, Kamouchi, Masahiro, Keene, Keith L., Kitazono, Takanari, Kittner, Steven J., Konuma, Takahiro, Kumar, Amit, Lacaze, Paul, Launer, Lenore J., Lee, Keon-Joo, Lepik, Kaido, Li, Jiang, Li, Liming, Manichaikul, Ani, Markus, Hugh S., Marston, Nicholas A., Meitinger, Thomas, Mitchell, Braxton D., Montellano, Felipe A., Morisaki, Takayuki, Mosley, Thomas H., Nalls, Mike A., Nordestgaard, Børge G., O'Donnell, Martin J., Okada, Yukinori, Onland-Moret, N. Charlotte, Ovbiagele, Bruce, Peters, Annette, Psaty, Bruce M., Rich, Stephen S., Rosand, Jonathan, Sabatine, Marc S., Sacco, Ralph L., Saleheen, Danish, Sandset, Else Charlotte, Salomaa, Veikko, Sargurupremraj, Muralidharan, Sasaki, Makoto, Satizabal, Claudia L., Schmidt, Carsten O., Shimizu, Atsushi, Smith, Nicholas L., Sloane, Kelly L., Sutoh, Yoichi, Sun, Yan V., Tanno, Kozo, Tiedt, Steffen, Tatlisumak, Turgut, Torres-Aguila, Nuria P., Tiwari, Hemant K., Trégouët, David-Alexandre, Trompet, Stella, Tuladhar, Anil Man, Tybjærg-Hansen, Anne, van Vugt, Marion, Vibo, Riina, Verma, Shefali S., Wiggins, Kerri L., Wennberg, Patrik, Woo, Daniel, Wilson, Peter W. F., Xu, Huichun, Yang, Qiong, Yoon, Kyungheon, Millwood, Iona Y., Gieger, Christian, Ninomiya, Toshiharu, Grabe, Hans J., Jukema, J. Wouter, Rissanen, Ina L., Strbian, Daniel, Kim, Young Jin, Chen, Pei-Hsin, Mayerhofer, Ernst, Howson, Joanna M. M., Irvin, Marguerite R., Adams, Hieab, Wassertheil-Smoller, Sylvia, Christensen, Kaare, Ikram, Mohammad A., Rundek, Tatjana, Worrall, Bradford B., Lathrop, G. Mark, Riaz, Moeen, Simonsick, Eleanor M., Kõrv, Janika, França, Paulo H. C., Zand, Ramin, Prasad, Kameshwar, Frikke-Schmidt, Ruth, de Leeuw, Frank-Erik, Liman, Thomas, Haeusler, Karl Georg, Ruigrok, Ynte M., Heuschmann, Peter Ulrich, Longstreth, W. T., Jung, Keum Ji, Bastarache, Lisa, Paré, Guillaume, Damrauer, Scott M., Chasman, Daniel I., Rotter, Jerome I., Anderson, Christopher D., Zwart, John-Anker, Niiranen, Teemu J., Fornage, Myriam, Liaw, Yung-Po, Seshadri, Sudha, Fernández-Cadenas, Israel, Walters, Robin G., Ruff, Christian T., Owolabi, Mayowa O., Huffman, Jennifer E., Milani, Lili, Kamatani, Yoichiro, Dichgans, Martin, Debette, Stephanie, Mishra, Aniket, Malik, Rainer, Hachiya, Tsuyoshi, Jürgenson, Tuuli, Namba, Shinichi, Posner, Daniel C., Kamanu, Frederick K., Koido, Masaru, Le Grand, Quentin, Shi, Mingyang, He, Yunye, Georgakis, Marios K., Caro, Ilana, Krebs, Kristi, Liaw, Yi-Ching, Vaura, Felix C., Lin, Kuang, Slagsvold Winsvold, Bendik, Srinivasasainagendra, Vinodh, Parodi, Livia, Bae, Hee-Joon, Chauhan, Ganesh, Chong, Michael R., Tomppo, Liisa, Akinyemi, Rufus, Roshchupkin, Gennady V., Habib, Naomi, Jee, Yon Ho, Thomassen, Jesper Qvist, Abedi, Vida, Cárcel-Márquez, Jara, Nygaard, Marianne, Leonard, Hampton L., Yang, Chaojie, Yonova-Doing, Ekaterina, Knol, Maria J., Lewis, Adam J., Judy, Renae L., Ago, Tetsuro, Amouyel, Philippe, Armstrong, Nicole D., Bakker, Mark K., Bartz, Traci M., Bennett, David A., Bis, Joshua C., Bordes, Constance, Børte, Sigrid, Cain, Anael, Ridker, Paul M., Cho, Kelly, Chen, Zhengming, Cruchaga, Carlos, Cole, John W., de Jager, Phil L., de Cid, Rafael, Endres, Matthias, Ferreira, Leslie E., Geerlings, Mirjam I., Gasca, Natalie C., Gudnason, Vilmundur, Hata, Jun, He, Jing, Heath, Alicia K., Ho, Yuk-Lam, Havulinna, Aki S., Hopewell, Jemma C., Hyacinth, Hyacinth I., Inouye, Michael, Jacob, Mina A., Jeon, Christina E., Jern, Christina, Kamouchi, Masahiro, Keene, Keith L., Kitazono, Takanari, Kittner, Steven J., Konuma, Takahiro, Kumar, Amit, Lacaze, Paul, Launer, Lenore J., Lee, Keon-Joo, Lepik, Kaido, Li, Jiang, Li, Liming, Manichaikul, Ani, Markus, Hugh S., Marston, Nicholas A., Meitinger, Thomas, Mitchell, Braxton D., Montellano, Felipe A., Morisaki, Takayuki, Mosley, Thomas H., Nalls, Mike A., Nordestgaard, Børge G., O'Donnell, Martin J., Okada, Yukinori, Onland-Moret, N. Charlotte, Ovbiagele, Bruce, Peters, Annette, Psaty, Bruce M., Rich, Stephen S., Rosand, Jonathan, Sabatine, Marc S., Sacco, Ralph L., Saleheen, Danish, Sandset, Else Charlotte, Salomaa, Veikko, Sargurupremraj, Muralidharan, Sasaki, Makoto, Satizabal, Claudia L., Schmidt, Carsten O., Shimizu, Atsushi, Smith, Nicholas L., Sloane, Kelly L., Sutoh, Yoichi, Sun, Yan V., Tanno, Kozo, Tiedt, Steffen, Tatlisumak, Turgut, Torres-Aguila, Nuria P., Tiwari, Hemant K., Trégouët, David-Alexandre, Trompet, Stella, Tuladhar, Anil Man, Tybjærg-Hansen, Anne, van Vugt, Marion, Vibo, Riina, Verma, Shefali S., Wiggins, Kerri L., Wennberg, Patrik, Woo, Daniel, Wilson, Peter W. F., Xu, Huichun, Yang, Qiong, Yoon, Kyungheon, Millwood, Iona Y., Gieger, Christian, Ninomiya, Toshiharu, Grabe, Hans J., Jukema, J. Wouter, Rissanen, Ina L., Strbian, Daniel, Kim, Young Jin, Chen, Pei-Hsin, Mayerhofer, Ernst, Howson, Joanna M. M., Irvin, Marguerite R., Adams, Hieab, Wassertheil-Smoller, Sylvia, Christensen, Kaare, Ikram, Mohammad A., Rundek, Tatjana, Worrall, Bradford B., Lathrop, G. Mark, Riaz, Moeen, Simonsick, Eleanor M., Kõrv, Janika, França, Paulo H. C., Zand, Ramin, Prasad, Kameshwar, Frikke-Schmidt, Ruth, de Leeuw, Frank-Erik, Liman, Thomas, Haeusler, Karl Georg, Ruigrok, Ynte M., Heuschmann, Peter Ulrich, Longstreth, W. T., Jung, Keum Ji, Bastarache, Lisa, Paré, Guillaume, Damrauer, Scott M., Chasman, Daniel I., Rotter, Jerome I., Anderson, Christopher D., Zwart, John-Anker, Niiranen, Teemu J., Fornage, Myriam, Liaw, Yung-Po, Seshadri, Sudha, Fernández-Cadenas, Israel, Walters, Robin G., Ruff, Christian T., Owolabi, Mayowa O., Huffman, Jennifer E., Milani, Lili, Kamatani, Yoichiro, Dichgans, Martin, and Debette, Stephanie
Abstract: Previous genome-wide association studies (GWASs) of stroke - the second leading cause of death worldwide - were conducted predominantly in populations of European ancestry1,2. Here, in cross-ancestry GWAS meta-analyses of 110,182 patients who have had a stroke (five ancestries, 33% non-European) and 1,503,898 control individuals, we identify association signals for stroke and its subtypes at 89 (61 new) independent loci: 60 in primary inverse-variance-weighted analyses and 29 in secondary meta-regression and multitrait analyses. On the basis of internal cross-ancestry validation and an independent follow-up in 89,084 additional cases of stroke (30% non-European) and 1,013,843 control individuals, 87% of the primary stroke risk loci and 60% of the secondary stroke risk loci were replicated (P < 0.05). Effect sizes were highly correlated across ancestries. Cross-ancestry fine-mapping, in silico mutagenesis analysis3, and transcriptome-wide and proteome-wide association analyses revealed putative causal genes (such as SH3PXD2A and FURIN) and variants (such as at GRK5 and NOS3). Using a three-pronged approach4, we provide genetic evidence for putative drug effects, highlighting F11, KLKB1, PROC, GP1BA, LAMC2 and VCAM1 as possible targets, with drugs already under investigation for stroke for F11 and PROC. A polygenic score integrating cross-ancestry and ancestry-specific stroke GWASs with vascular-risk factor GWASs (integrative polygenic scores) strongly predicted ischaemic stroke in populations of European, East Asian and African ancestry5. Stroke genetic risk scores were predictive of ischaemic stroke independent of clinical risk factors in 52,600 clinical-trial participants with cardiometabolic disease. Our results provide insights to inform biology, reveal potential drug targets and derive genetic risk prediction tools across ancestries., Publisher correction: Mishra, A., Malik, R., Hachiya, T. et al. Publisher Correction: Stroke genetics informs drug discovery and risk prediction across ancestries. Nature 612, E7 (2022). DOI: 10.1038/s41586-022-05492-5
Published: 2022
Full Text: View/download PDF

29. Stroke genetics informs drug discovery and risk prediction across ancestries

Author: Mishra, Aniket, Malik, Rainer, Hachiya, Tsuyoshi, Jürgenson, Tuuli, Namba, Shinichi, Posner, Daniel C., Kamanu, Frederick K., Koido, Masaru, Le Grand, Quentin, Shi, Mingyang, He, Yunye, Georgakis, Marios K., Caro, Ilana, Krebs, Kristi, Liaw, Yi-Ching, Vaura, Felix C., Lin, Kuang, Slagsvold Winsvold, Bendik, Srinivasasainagendra, Vinodh, Parodi, Livia, Bae, Hee-Joon, Chauhan, Ganesh, Chong, Michael R., Tomppo, Liisa, Akinyemi, Rufus, Roshchupkin, Gennady V., Habib, Naomi, Jee, Yon Ho, Thomassen, Jesper Qvist, Abedi, Vida, Cárcel-Márquez, Jara, Nygaard, Marianne, Leonard, Hampton L., Yang, Chaojie, Yonova-Doing, Ekaterina, Knol, Maria J., Lewis, Adam J., Judy, Renae L., Ago, Tetsuro, Amouyel, Philippe, Armstrong, Nicole D., Bakker, Mark K., Bartz, Traci M., Bennett, David A., Bis, Joshua C., Bordes, Constance, Børte, Sigrid, Cain, Anael, Ridker, Paul M., Cho, Kelly, Chen, Zhengming, Cruchaga, Carlos, Cole, John W., de Jager, Phil L., de Cid, Rafael, Endres, Matthias, Ferreira, Leslie E., Geerlings, Mirjam I., Gasca, Natalie C., Gudnason, Vilmundur, Hata, Jun, He, Jing, Heath, Alicia K., Ho, Yuk-Lam, Havulinna, Aki S., Hopewell, Jemma C., Hyacinth, Hyacinth I., Inouye, Michael, Jacob, Mina A., Jeon, Christina E., Jern, Christina, Kamouchi, Masahiro, Keene, Keith L., Kitazono, Takanari, Kittner, Steven J., Konuma, Takahiro, Kumar, Amit, Lacaze, Paul, Launer, Lenore J., Lee, Keon-Joo, Lepik, Kaido, Li, Jiang, Li, Liming, Manichaikul, Ani, Markus, Hugh S., Marston, Nicholas A., Meitinger, Thomas, Mitchell, Braxton D., Montellano, Felipe A., Morisaki, Takayuki, Mosley, Thomas H., Nalls, Mike A., Nordestgaard, Børge G., O'Donnell, Martin J., Okada, Yukinori, Onland-Moret, N. Charlotte, Ovbiagele, Bruce, Peters, Annette, Psaty, Bruce M., Rich, Stephen S., Rosand, Jonathan, Sabatine, Marc S., Sacco, Ralph L., Saleheen, Danish, Sandset, Else Charlotte, Salomaa, Veikko, Sargurupremraj, Muralidharan, Sasaki, Makoto, Satizabal, Claudia L., Schmidt, Carsten O., Shimizu, Atsushi, Smith, Nicholas L., Sloane, Kelly L., Sutoh, Yoichi, Sun, Yan V., Tanno, Kozo, Tiedt, Steffen, Tatlisumak, Turgut, Torres-Aguila, Nuria P., Tiwari, Hemant K., Trégouët, David-Alexandre, Trompet, Stella, Tuladhar, Anil Man, Tybjærg-Hansen, Anne, van Vugt, Marion, Vibo, Riina, Verma, Shefali S., Wiggins, Kerri L., Wennberg, Patrik, Woo, Daniel, Wilson, Peter W. F., Xu, Huichun, Yang, Qiong, Yoon, Kyungheon, Millwood, Iona Y., Gieger, Christian, Ninomiya, Toshiharu, Grabe, Hans J., Jukema, J. Wouter, Rissanen, Ina L., Strbian, Daniel, Kim, Young Jin, Chen, Pei-Hsin, Mayerhofer, Ernst, Howson, Joanna M. M., Irvin, Marguerite R., Adams, Hieab, Wassertheil-Smoller, Sylvia, Christensen, Kaare, Ikram, Mohammad A., Rundek, Tatjana, Worrall, Bradford B., Lathrop, G. Mark, Riaz, Moeen, Simonsick, Eleanor M., Kõrv, Janika, França, Paulo H. C., Zand, Ramin, Prasad, Kameshwar, Frikke-Schmidt, Ruth, de Leeuw, Frank-Erik, Liman, Thomas, Haeusler, Karl Georg, Ruigrok, Ynte M., Heuschmann, Peter Ulrich, Longstreth, W. T., Jung, Keum Ji, Bastarache, Lisa, Paré, Guillaume, Damrauer, Scott M., Chasman, Daniel I., Rotter, Jerome I., Anderson, Christopher D., Zwart, John-Anker, Niiranen, Teemu J., Fornage, Myriam, Liaw, Yung-Po, Seshadri, Sudha, Fernández-Cadenas, Israel, Walters, Robin G., Ruff, Christian T., Owolabi, Mayowa O., Huffman, Jennifer E., Milani, Lili, Kamatani, Yoichiro, Dichgans, Martin, Debette, Stephanie, Mishra, Aniket, Malik, Rainer, Hachiya, Tsuyoshi, Jürgenson, Tuuli, Namba, Shinichi, Posner, Daniel C., Kamanu, Frederick K., Koido, Masaru, Le Grand, Quentin, Shi, Mingyang, He, Yunye, Georgakis, Marios K., Caro, Ilana, Krebs, Kristi, Liaw, Yi-Ching, Vaura, Felix C., Lin, Kuang, Slagsvold Winsvold, Bendik, Srinivasasainagendra, Vinodh, Parodi, Livia, Bae, Hee-Joon, Chauhan, Ganesh, Chong, Michael R., Tomppo, Liisa, Akinyemi, Rufus, Roshchupkin, Gennady V., Habib, Naomi, Jee, Yon Ho, Thomassen, Jesper Qvist, Abedi, Vida, Cárcel-Márquez, Jara, Nygaard, Marianne, Leonard, Hampton L., Yang, Chaojie, Yonova-Doing, Ekaterina, Knol, Maria J., Lewis, Adam J., Judy, Renae L., Ago, Tetsuro, Amouyel, Philippe, Armstrong, Nicole D., Bakker, Mark K., Bartz, Traci M., Bennett, David A., Bis, Joshua C., Bordes, Constance, Børte, Sigrid, Cain, Anael, Ridker, Paul M., Cho, Kelly, Chen, Zhengming, Cruchaga, Carlos, Cole, John W., de Jager, Phil L., de Cid, Rafael, Endres, Matthias, Ferreira, Leslie E., Geerlings, Mirjam I., Gasca, Natalie C., Gudnason, Vilmundur, Hata, Jun, He, Jing, Heath, Alicia K., Ho, Yuk-Lam, Havulinna, Aki S., Hopewell, Jemma C., Hyacinth, Hyacinth I., Inouye, Michael, Jacob, Mina A., Jeon, Christina E., Jern, Christina, Kamouchi, Masahiro, Keene, Keith L., Kitazono, Takanari, Kittner, Steven J., Konuma, Takahiro, Kumar, Amit, Lacaze, Paul, Launer, Lenore J., Lee, Keon-Joo, Lepik, Kaido, Li, Jiang, Li, Liming, Manichaikul, Ani, Markus, Hugh S., Marston, Nicholas A., Meitinger, Thomas, Mitchell, Braxton D., Montellano, Felipe A., Morisaki, Takayuki, Mosley, Thomas H., Nalls, Mike A., Nordestgaard, Børge G., O'Donnell, Martin J., Okada, Yukinori, Onland-Moret, N. Charlotte, Ovbiagele, Bruce, Peters, Annette, Psaty, Bruce M., Rich, Stephen S., Rosand, Jonathan, Sabatine, Marc S., Sacco, Ralph L., Saleheen, Danish, Sandset, Else Charlotte, Salomaa, Veikko, Sargurupremraj, Muralidharan, Sasaki, Makoto, Satizabal, Claudia L., Schmidt, Carsten O., Shimizu, Atsushi, Smith, Nicholas L., Sloane, Kelly L., Sutoh, Yoichi, Sun, Yan V., Tanno, Kozo, Tiedt, Steffen, Tatlisumak, Turgut, Torres-Aguila, Nuria P., Tiwari, Hemant K., Trégouët, David-Alexandre, Trompet, Stella, Tuladhar, Anil Man, Tybjærg-Hansen, Anne, van Vugt, Marion, Vibo, Riina, Verma, Shefali S., Wiggins, Kerri L., Wennberg, Patrik, Woo, Daniel, Wilson, Peter W. F., Xu, Huichun, Yang, Qiong, Yoon, Kyungheon, Millwood, Iona Y., Gieger, Christian, Ninomiya, Toshiharu, Grabe, Hans J., Jukema, J. Wouter, Rissanen, Ina L., Strbian, Daniel, Kim, Young Jin, Chen, Pei-Hsin, Mayerhofer, Ernst, Howson, Joanna M. M., Irvin, Marguerite R., Adams, Hieab, Wassertheil-Smoller, Sylvia, Christensen, Kaare, Ikram, Mohammad A., Rundek, Tatjana, Worrall, Bradford B., Lathrop, G. Mark, Riaz, Moeen, Simonsick, Eleanor M., Kõrv, Janika, França, Paulo H. C., Zand, Ramin, Prasad, Kameshwar, Frikke-Schmidt, Ruth, de Leeuw, Frank-Erik, Liman, Thomas, Haeusler, Karl Georg, Ruigrok, Ynte M., Heuschmann, Peter Ulrich, Longstreth, W. T., Jung, Keum Ji, Bastarache, Lisa, Paré, Guillaume, Damrauer, Scott M., Chasman, Daniel I., Rotter, Jerome I., Anderson, Christopher D., Zwart, John-Anker, Niiranen, Teemu J., Fornage, Myriam, Liaw, Yung-Po, Seshadri, Sudha, Fernández-Cadenas, Israel, Walters, Robin G., Ruff, Christian T., Owolabi, Mayowa O., Huffman, Jennifer E., Milani, Lili, Kamatani, Yoichiro, Dichgans, Martin, and Debette, Stephanie
Abstract: Previous genome-wide association studies (GWASs) of stroke - the second leading cause of death worldwide - were conducted predominantly in populations of European ancestry1,2. Here, in cross-ancestry GWAS meta-analyses of 110,182 patients who have had a stroke (five ancestries, 33% non-European) and 1,503,898 control individuals, we identify association signals for stroke and its subtypes at 89 (61 new) independent loci: 60 in primary inverse-variance-weighted analyses and 29 in secondary meta-regression and multitrait analyses. On the basis of internal cross-ancestry validation and an independent follow-up in 89,084 additional cases of stroke (30% non-European) and 1,013,843 control individuals, 87% of the primary stroke risk loci and 60% of the secondary stroke risk loci were replicated (P < 0.05). Effect sizes were highly correlated across ancestries. Cross-ancestry fine-mapping, in silico mutagenesis analysis3, and transcriptome-wide and proteome-wide association analyses revealed putative causal genes (such as SH3PXD2A and FURIN) and variants (such as at GRK5 and NOS3). Using a three-pronged approach4, we provide genetic evidence for putative drug effects, highlighting F11, KLKB1, PROC, GP1BA, LAMC2 and VCAM1 as possible targets, with drugs already under investigation for stroke for F11 and PROC. A polygenic score integrating cross-ancestry and ancestry-specific stroke GWASs with vascular-risk factor GWASs (integrative polygenic scores) strongly predicted ischaemic stroke in populations of European, East Asian and African ancestry5. Stroke genetic risk scores were predictive of ischaemic stroke independent of clinical risk factors in 52,600 clinical-trial participants with cardiometabolic disease. Our results provide insights to inform biology, reveal potential drug targets and derive genetic risk prediction tools across ancestries., Publisher correction: Mishra, A., Malik, R., Hachiya, T. et al. Publisher Correction: Stroke genetics informs drug discovery and risk prediction across ancestries. Nature 612, E7 (2022). DOI: 10.1038/s41586-022-05492-5
Published: 2022
Full Text: View/download PDF

30. Behavior of geodesic acoustic mode and limit-cycle oscillation approaching L-H transition in JFT-2M tokamak

Author: KOBAYASHI, Tatsuya, SASAKI, Makoto, IDO, Takeshi, KAMIYA, Kensaku, MIURA, Y, IDA, Katsumi, ITOH, Kimitaka, KOBAYASHI, Tatsuya, SASAKI, Makoto, IDO, Takeshi, KAMIYA, Kensaku, MIURA, Y, IDA, Katsumi, and ITOH, Kimitaka
Abstract: 0000-0001-5669-1937, In this paper, a phenomenology of competing behavior between the geodesic acoustic mode (GAM) and the limit-cycle oscillation (LCO) is presented. Before the LCO occurs, the GAM can grow to the observable amplitude via the turbulent Reynolds stress force. Approaching the L-H transition, the LCO is excited and the GAM decays. In the LCO phase, the GAM driving force is possibly suppressed by the nonlocal turbulence amplitude modulation by the LCO.
Published: 2022

31. Spatiotemporal dynamics of high-wavenumber turbulence in a basic laboratory plasma

Author: KAWACHI, Yuichi, SASAKI, Makoto, KOSUGA, Yusuke, TERASAKA, Kenichiro, NISHIZAWA, Takashi, YAMADA, Takuma, KASUYA, Naohiro, MOON, Chanho, INAGAKI, Shigeru, KAWACHI, Yuichi, SASAKI, Makoto, KOSUGA, Yusuke, TERASAKA, Kenichiro, NISHIZAWA, Takashi, YAMADA, Takuma, KASUYA, Naohiro, MOON, Chanho, and INAGAKI, Shigeru
Abstract: 0000-0002-5222-6082, High-spatial resolution observation of high-wavenumber broadband turbulence is achieved by controlling the magnetic field to be relatively low and measuring with a azimuthally arranged multi-channel Langmuir array in a basic laboratory plasma. The observed turbulence consists of narrowband low-frequency fluctuations and broadband high-frequency turbulent fluctuations. The low-frequency fluctuations have a frequency of about 0.7 times the ion cyclotron frequency and a spatial scale of 1/10 of the ion inertial scale. In comparison, high-frequency fluctuations have a higher frequency than the ion cyclotron frequency and spatial scales of 1/10–1/40 of the ion inertial scale. Two-dimensional correlation analysis evaluates the spatial and temporal correlation lengths and reveals that the high-wavenumber broadband fluctuations have turbulent characteristics. The measurements give us further understanding of small scale turbulence in space and fusion plasmas.
Published: 2022

32. Determination of the toxicity equivalency factors for ciguatoxins using human sodium channels

Author: Universidade de Santiago de Compostela. Departamento de Farmacoloxía, Farmacia e Tecnoloxía Farmacéutica, Universidade de Santiago de Compostela. Facultade de Veterinaria, Raposo García, Sandra, Louzao Ojeda, María Carmen, Fuwa, Haruhiko, Sasaki, Makoto, Vale González, María del Carmen, Botana López, Luis Miguel, Universidade de Santiago de Compostela. Departamento de Farmacoloxía, Farmacia e Tecnoloxía Farmacéutica, Universidade de Santiago de Compostela. Facultade de Veterinaria, Raposo García, Sandra, Louzao Ojeda, María Carmen, Fuwa, Haruhiko, Sasaki, Makoto, Vale González, María del Carmen, and Botana López, Luis Miguel
Abstract: Ciguatoxins (CTXs) which are produced by dinoflagellates of the genus Gambierdiscus and Fukuyoa and share a ladder-shaped polyether structure, are causative compounds of one of the most frequent foodborne illness disease known as ciguatera fish poisoning (CFP). CFP was initially found in tropical and subtropical areas but nowadays the dinoflagellates producers of ciguatoxins had spread to European coasts. Therefore, this raises the need of establishing toxicity equivalency factors for the different compounds that can contribute to ciguatera fish poisoning, since biological methods have been replaced by analytical techniques. Thus, in this work, the effects of six compounds causative of ciguatera, on their main target, the human voltage-gated sodium channels have been analyzed for the first time. The results presented here led to the conclusion that the order of potency was CTX1B, CTX3B, CTX4A, gambierol, gambierone and MTX3. Furthermore, the data indicate that the activation voltage of sodium channels is more sensitive to detect ciguatoxins than their effect on the peak sodium current amplitude
Published: 2022

33. Dosimetric advantages of daily adaptive strategy in IMPT for high-risk prostate cancer

Author: Tamura, Hiroshi, Kobashi, Keiji, Nishioka, Kentaro, Yoshimura, Takaaki, Hashimoto, Takayuki, Shimizu, Shinichi, Ito, Yoichi M., Maeda, Yoshikazu, Sasaki, Makoto, Yamamoto, Kazutaka, Tamamura, Hiroyasu, Aoyama, Hidefumi, Shirato, Hiroki, Tamura, Hiroshi, Kobashi, Keiji, Nishioka, Kentaro, Yoshimura, Takaaki, Hashimoto, Takayuki, Shimizu, Shinichi, Ito, Yoichi M., Maeda, Yoshikazu, Sasaki, Makoto, Yamamoto, Kazutaka, Tamamura, Hiroyasu, Aoyama, Hidefumi, and Shirato, Hiroki
Abstract: Purpose To evaluate the dosimetric advantages of daily adaptive radiotherapy (DART) in intensity-modulated proton therapy (IMPT) for high-risk prostate cancer by comparing estimated doses of the conventional non-adaptive radiotherapy (NART) that irradiates according to an original treatment plan through the entire treatment and the DART that uses an adaptive treatment plan generated by using daily CT images acquired before each treatment. Methods Twenty-three patients with prostate cancer were included. A treatment plan with 63 Gy (relative biological effectiveness (RBE)) in 21 fractions was generated using treatment planning computed tomography (CT) images assuming that all patients had high-risk prostate cancer for which the clinical target volume (CTV) needs to include prostate and the seminal vesicle (SV) in our treatment protocol. Twenty-one adaptive treatment plans for each patient (total 483 data sets) were generated using daily CT images, and dose distributions were calculated. Using a 3 mm set-up uncertainty in the robust optimization, the doses to the CTV, prostate, SV, rectum, and bladder were compared. Results Estimated accumulated doses of NART and DART in the 23 patients were 60.81 +/- 3.47 Gy (RBE) and 63.24 +/- 1.04 Gy (RBE) for CTV D99 (p < 0.01), 62.99 +/- 1.28 Gy (RBE) and 63.43 +/- 1.33 Gy (RBE) for the prostate D99 (p = 0.2529), and 59.07 +/- 5.19 Gy (RBE) and 63.17 +/- 1.04 Gy (RBE) for SV D99 (p < 0.001). No significant differences were observed between NART and DART in the estimated accumulated dose for the rectum and bladder. Conclusion Compared with the NART, DART was shown to be a useful approach that can maintain the dose coverage to the target without increasing the dose to the organs at risk (OAR) using the 3 mm set-up uncertainty in the robust optimization in patients with high-risk prostate cancer.
Published: 2022

34. Stroke genetics informs drug discovery and risk prediction across ancestries

Author: Mishra, Aniket, Malik, Rainer, Hachiya, Tsuyoshi, Jurgenson, Tuuli, Namba, Shinichi, Posner, Daniel C, Kamanu, Frederick K, Koido, Masaru, Le Grand, Quentin, Shi, Mingyang, He, Yunye, Georgakis, Marios K, Caro, Ilana, Krebs, Kristi, Liaw, Yi-Ching, Vaura, Felix C, Lin, Kuang, Winsvold, Bendik Slagsvold, Srinivasasainagendra, Vinodh, Parodi, Livia, Bae, Hee-Joon, Chauhan, Ganesh, Chong, Michael R, Tomppo, Liisa, Akinyemi, Rufus, Roshchupkin, Gennady V, Habib, Naomi, Jee, Yon Ho, Thomassen, Jesper Qvist, Abedi, Vida, Carcel-Marquez, Jara, Nygaard, Marianne, Leonard, Hampton L, Yang, Chaojie, Yonova-Doing, Ekaterina, Knol, Maria J, Lewis, Adam J, Judy, Renae L, Ago, Tetsuro, Amouyel, Philippe, Armstrong, Nicole D, Bakker, Mark K, Bartz, Traci M, Bennett, David A, Bis, Joshua C, Bordes, Constance, Borte, Sigrid, Cain, Anael, Ridker, Paul M, Cho, Kelly, Chen, Zhengming, Cruchaga, Carlos, Cole, John W, de Jager, Phil L, de Cid, Rafael, Endres, Matthias, Ferreira, Leslie E, Geerlings, Mirjam I, Gasca, Natalie C, Gudnason, Vilmundur, Hata, Jun, He, Jing, Heath, Alicia K, Ho, Yuk-Lam, Havulinna, Aki S, Hopewell, Jemma C, Hyacinth, Hyacinth I, Inouye, Michael, Jacob, Mina A, Jeon, Christina E, Jern, Christina, Kamouchi, Masahiro, Keene, Keith L, Kitazono, Takanari, Kittner, Steven J, Konuma, Takahiro, Kumar, Amit, Lacaze, Paul, Launer, Lenore J, Lee, Keon-Joo, Lepik, Kaido, Li, Jiang, Li, Liming, Manichaikul, Ani, Markus, Hugh S, Marston, Nicholas A, Meitinger, Thomas, Mitchell, Braxton D, Montellano, Felipe A, Morisaki, Takayuki, Mosley, Thomas H, Nalls, Mike A, Nordestgaard, Borge G, O'Donnell, Martin J, Okada, Yukinori, Onland-Moret, N Charlotte, Ovbiagele, Bruce, Peters, Annette, Psaty, Bruce M, Rich, Stephen S, Rosand, Jonathan, Sabatine, Marc S, Sacco, Ralph L, Saleheen, Danish, Sandset, Else Charlotte, Salomaa, Veikko, Sargurupremraj, Muralidharan, Sasaki, Makoto, Satizabal, Claudia L, Schmidt, Carsten O, Shimizu, Atsushi, Smith, Nicholas L, Sloane, Kelly L, Sutoh, Yoichi, Sun, Yan V, Tanno, Kozo, Tiedt, Steffen, Tatlisumak, Turgut, Torres-Aguila, Nuria P, Tiwari, Hemant K, Tregouet, David-Alexandre, Trompet, Stella, Tuladhar, Anil Man, Tybjaerg-Hansen, Anne, van Vugt, Marion, Vibo, Riina, Verma, Shefali S, Wiggins, Kerri L, Wennberg, Patrik, Woo, Daniel, Wilson, Peter WF, Xu, Huichun, Yang, Qiong, Yoon, Kyungheon, Lee, Jin-Moo, Cheng, Yu-Ching, Meschia, James F, Chen, Wei Min, Sale, Michele M, Zonderman, Alan B, Evans, Michele K, Wilson, James G, Correa, Adolfo, Traylor, Matthew, Lewis, Cathryn M, Carty, Cara L, Reiner, Alexander, Haessler, Jeffrey, Langefeld, Carl D, Gottesman, Rebecca F, Yaffe, Kristine, Liu, Yong Mei, Kooperberg, Charles, Lange, Leslie A, Furie, Karen L, Arnett, Donna K, Benavente, Oscar R, Grewal, Raji P, Peddareddygari, Leema Reddy, Hveem, Kristian, Lindstrom, Sara, Wang, Lu, Smith, Erin N, Gordon, William, van Hylckama Vlieg, Astrid, de Andrade, Mariza, Brody, Jennifer A, Pattee, Jack W, Brumpton, Ben M, Suchon, Pierre, Chen, Ming-Huei, Frazer, Kelly A, Turman, Constance, Germain, Marine, MacDonald, James, Braekkan, Sigrid K, Armasu, Sebastian M, Pankratz, Nathan, Jackson, Rebecca D, Nielsen, Jonas B, Giulianini, Franco, Puurunen, Marja K, Ibrahim, Manal, Heckbert, Susan R, Bammler, Theo K, McCauley, Bryan M, Taylor, Kent D, Pankow, James S, Reiner, Alexander P, Gabrielsen, Maiken E, Deleuze, Jean-Francois, O'Donnell, Chris J, Kim, Jihye, McKnight, Barbara, Kraft, Peter, Hansen, John-Bjarne, Rosendaal, Frits R, Heit, John A, Tang, Weihong, Morange, Pierre-Emmanuel, Johnson, Andrew D, Kabrhel, Christopher, van Dijk, Ewoud J, Koudstaal, Peter J, Luijckx, Gert-Jan, Nederkoorn, Paul J, van Oostenbrugge, Robert J, Visser, Marieke C, Wermer, Marieke JH, Kappelle, L Jaap, Esko, Tonu, Metspalu, Andres, Magi, Reedik, Nelis, Mari, Irvin, Marguerite R, de Leeuw, Frank-Erik, Levi, Christopher R, Maguire, Jane, Jimenez-Conde, Jordi, Sharma, Pankaj, Sudlow, Cathie LM, Rannikmae, Kristiina, Schmidt, Reinhold, Slowik, Agnieszka, Pera, Joanna, Thijs, Vincent NS, Lindgren, Arne G, Ilinca, Andreea, Melander, Olle, Engstrom, Gunnar, Rexrode, Kathryn M, Rothwell, Peter M, Stanne, Tara M, Johnson, Julie A, Danesh, John, Butterworth, Adam S, Heitsch, Laura, Boncoraglio, Giorgio B, Kubo, Michiaki, Pezzini, Alessandro, Rolfs, Arndt, Giese, Anne-Katrin, Weir, David, Ross, Owen A, Lemmons, Robin, Soderholm, Martin, Cushman, Mary, Jood, Katarina, McDonough, Caitrin W, Bell, Steven, Linkohr, Birgit, Lee, Tsong-Hai, Putaala, Jukka, Anderson, Christopher D, Lopez, Oscar L, Jian, Xueqiu, Schminke, Ulf, Cullell, Natalia, Delgado, Pilar, Ibanez, Laura, Krupinski, Jerzy, Lioutas, Vasileios, Matsuda, Koichi, Montaner, Joan, Muino, Elena, Roquer, Jaume, Sarnowski, Chloe, Sattar, Naveed, Sibolt, Gerli, Teumer, Alexander, Rutten-Jacobs, Loes, Kanai, Masahiro, Gretarsdottir, Solveig, Rost, Natalia S, Yusuf, Salim, Almgren, Peter, Ay, Hakan, Bevan, Steve, Brown, Robert D, Carrera, Caty, Buring, Julie E, Chen, Wei-Min, Cotlarciuc, Ioana, de Bakker, Paul IW, DeStefano, Anita L, den Hoed, Marcel, Duan, Qing, Engelter, Stefan T, Falcone, Guido J, Gustafsson, Stefan, Hassan, Ahamad, Holliday, Elizabeth G, Howard, George, Hsu, Fang-Chi, Ingelsson, Erik, Harris, Tamara B, Kissela, Brett M, Kleindorfer, Dawn O, Langenberg, Claudia, Lemmens, Robin, Leys, Didier, Lin, Wei-Yu, Lorentzen, Erik, Magnusson, Patrik K, McArdle, Patrick F, Pulit, Sara L, Rice, Kenneth, Sakaue, Saori, Sapkota, Bishwa R, Tanislav, Christian, Thorleifsson, Gudmar, Thorsteinsdottir, Unnur, Tzourio, Christophe, van Duijn, Cornelia M, Walters, Matthew, Wareham, Nicholas J, Amin, Najaf, Aparicio, Hugo J, Attia, John, Beiser, Alexa S, Berr, Claudine, Bustamante, Mariana, Caso, Valeria, Choi, Seung Hoan, Chowhan, Ayesha, Dartigues, Jean-Francois, Delavaran, Hossein, Dorr, Marcus, Ford, Ian, Gurpreet, Wander S, Hamsten, Anders, Hozawa, Atsushi, Ingelsson, Martin, Iwasaki, Motoki, Kaffashian, Sara, Kalra, Lalit, Kjartansson, Olafur, Kloss, Manja, Labovitz, Daniel L, Laurie, Cathy C, Li, Linxin, Lind, Lars, Lindgren, Cecilia M, Makoto, Hirata, Minegishi, Naoko, Morris, Andrew P, Muller-Nurasyid, Martina, Norrving, Bo, Ogishima, Soichi, Parati, Eugenio A, Pedersen, Nancy L, Perola, Markus, Jousilahti, Pekka, Pileggi, Silvana, Rabionet, Raquel, Riba-Llena, Iolanda, Ribases, Marta, Romero, Jose R, Rudd, Anthony G, Sarin, Antti-Pekka, Sarju, Ralhan, Satoh, Mamoru, Sawada, Norie, Sigurdsson, Asgeir, Smith, Albert, Stine, O Colin, Stott, David J, Strauch, Konstantin, Takai, Takako, Tanaka, Hideo, Touze, Emmanuel, Tsugane, Shoichiro, Uitterlinden, Andre G, Valdimarsson, Einar M, van der Lee, Sven J, Wakai, Kenji, Williams, Stephen R, Wolfe, Charles DA, Wong, Quenna, Yamaji, Taiki, Sanghera, Dharambir K, Stefansson, Kari, Martinez-Majander, Nicolas, Sobue, Kenji, Soriano-Tarraga, Carolina, Volzke, Henry, Akpa, Onoja, Sarfo, Fred S, Akpalu, Albert, Obiako, Reginald, Wahab, Kolawole, Osaigbovo, Godwin, Owolabi, Lukman, Komolafe, Morenikeji, Jenkins, Carolyn, Arulogun, Oyedunni, Ogbole, Godwin, Adeoye, Abiodun M, Akinyemi, Joshua, Agunloye, Atinuke, Fakunle, Adekunle G, Uvere, Ezinne, Olalere, Abimbola, Adebajo, Olayinka J, Chen, Junshi, Clarke, Robert, Collins, Rory, Guo, Yu, Wang, Chen, Lv, Jun, Peto, Richard, Chen, Yiping, Fairhurst-Hunter, Zammy, Hill, Michael, Pozarickij, Alfred, Schmidt, Dan, Stevens, Becky, Turnbull, Iain, Yu, Canqing, Nagai, Akiko, Murakami, Yoishinori, Shiroma, Eric J, Sigurdsson, Sigurdur, Ghanbari, Mohsen, Boerwinkle, Eric, Fongang, Bernard, Wang, Ruiqi, Ikram, Mohammad K, Volker, Uwe, de Laat, Karlijn F, van Norden, Anouk GW, de Kort, Paul L, Vermeer, Sarah E, Brouwers, Paul JAM, Gons, Rob AR, den Heijer, Tom, van Dijk, Gert W, van Rooij, Frank GW, Aamodt, Anne H, Skogholt, Anne H, Willer, Cristen J, Heuch, Ingrid, Hagen, Knut, Fritsche, Lars G, Pedersen, Linda M, Ellekjaer, Hanne, Zhou, Wei, Martinsen, Amy E, Kristoffersen, Espen S, Thomas, Laurent F, Kleinschnitz, Christoph, Frantz, Stefan, Ungethum, Kathrin, Gallego-Fabrega, Cristina, Lledos, Miquel, Llucia-Carol, Laia, Sobrino, Tomas, Campos, Francisco, Castillo, Jose, Freijo, Marimar, Arenillas, Juan Francisco, Obach, Victor, Alvarez-Sabin, Jose, Molina, Carlos A, Ribo, Marc, Munoz-Narbona, Lucia, Lopez-Cancio, Elena, Millan, Monica, Diaz-Navarro, Rosa, Vives-Bauza, Cristofol, Serrano-Heras, Gemma, Segura, Tomas, Dhar, Rajat, Delgado-Mederos, Raquel, Prats-Sanchez, Luis, Camps-Renom, Pol, Blay, Natalia, Sumoy, Lauro, Marti-Fabregas, Joan, Schnohr, Peter, Jensen, Gorm B, Benn, Marianne, Afzal, Shoaib, Kamstrup, Pia R, van Setten, Jessica, van der Laan, Sander W, Vonk, Jet MJ, Kim, Bong-Jo, Curtze, Sami, Tiainen, Marjaana, Kinnunen, Janne, Menon, Vilas, Sung, Yun Ju, Yang, Chengran, Saillour-Glenisson, Florence, Gravel, Simon, Millwood, Iona Y, Gieger, Christian, Ninomiya, Toshiharu, Grabe, Hans J, Jukema, J Wouter, Rissanen, Ina L, Strbian, Daniel, Kim, Young Jin, Chen, Pei-Hsin, Mayerhofer, Ernst, Howson, Joanna MM, Adams, Hieab, Wassertheil-Smoller, Sylvia, Christensen, Kaare, Ikram, Mohammad A, Rundek, Tatjana, Worrall, Bradford B, Lathrop, G Mark, Riaz, Moeen, Simonsick, Eleanor M, Korv, Janika, Franca, Paulo HC, Zand, Ramin, Prasad, Kameshwar, Frikke-Schmidt, Ruth, Liman, Thomas, Haeusler, Karl Georg, Ruigrok, Ynte M, Heuschmann, Peter Ulrich, Longstreth, WT, Jung, Keum Ji, Bastarache, Lisa, Pare, Guillaume, Damrauer, Scott M, Chasman, Daniel I, Rotter, Jerome I, Zwart, John-Anker, Niiranen, Teemu J, Fornage, Myriam, Liaw, Yung-Po, Seshadri, Sudha, Fernandez-Cadenas, Israel, Walters, Robin G, Ruff, Christian T, Owolabi, Mayowa O, Huffman, Jennifer E, Milani, Lili, Kamatani, Yoichiro, Dichgans, Martin, Debette, Stephanie, Mishra, Aniket, Malik, Rainer, Hachiya, Tsuyoshi, Jurgenson, Tuuli, Namba, Shinichi, Posner, Daniel C, Kamanu, Frederick K, Koido, Masaru, Le Grand, Quentin, Shi, Mingyang, He, Yunye, Georgakis, Marios K, Caro, Ilana, Krebs, Kristi, Liaw, Yi-Ching, Vaura, Felix C, Lin, Kuang, Winsvold, Bendik Slagsvold, Srinivasasainagendra, Vinodh, Parodi, Livia, Bae, Hee-Joon, Chauhan, Ganesh, Chong, Michael R, Tomppo, Liisa, Akinyemi, Rufus, Roshchupkin, Gennady V, Habib, Naomi, Jee, Yon Ho, Thomassen, Jesper Qvist, Abedi, Vida, Carcel-Marquez, Jara, Nygaard, Marianne, Leonard, Hampton L, Yang, Chaojie, Yonova-Doing, Ekaterina, Knol, Maria J, Lewis, Adam J, Judy, Renae L, Ago, Tetsuro, Amouyel, Philippe, Armstrong, Nicole D, Bakker, Mark K, Bartz, Traci M, Bennett, David A, Bis, Joshua C, Bordes, Constance, Borte, Sigrid, Cain, Anael, Ridker, Paul M, Cho, Kelly, Chen, Zhengming, Cruchaga, Carlos, Cole, John W, de Jager, Phil L, de Cid, Rafael, Endres, Matthias, Ferreira, Leslie E, Geerlings, Mirjam I, Gasca, Natalie C, Gudnason, Vilmundur, Hata, Jun, He, Jing, Heath, Alicia K, Ho, Yuk-Lam, Havulinna, Aki S, Hopewell, Jemma C, Hyacinth, Hyacinth I, Inouye, Michael, Jacob, Mina A, Jeon, Christina E, Jern, Christina, Kamouchi, Masahiro, Keene, Keith L, Kitazono, Takanari, Kittner, Steven J, Konuma, Takahiro, Kumar, Amit, Lacaze, Paul, Launer, Lenore J, Lee, Keon-Joo, Lepik, Kaido, Li, Jiang, Li, Liming, Manichaikul, Ani, Markus, Hugh S, Marston, Nicholas A, Meitinger, Thomas, Mitchell, Braxton D, Montellano, Felipe A, Morisaki, Takayuki, Mosley, Thomas H, Nalls, Mike A, Nordestgaard, Borge G, O'Donnell, Martin J, Okada, Yukinori, Onland-Moret, N Charlotte, Ovbiagele, Bruce, Peters, Annette, Psaty, Bruce M, Rich, Stephen S, Rosand, Jonathan, Sabatine, Marc S, Sacco, Ralph L, Saleheen, Danish, Sandset, Else Charlotte, Salomaa, Veikko, Sargurupremraj, Muralidharan, Sasaki, Makoto, Satizabal, Claudia L, Schmidt, Carsten O, Shimizu, Atsushi, Smith, Nicholas L, Sloane, Kelly L, Sutoh, Yoichi, Sun, Yan V, Tanno, Kozo, Tiedt, Steffen, Tatlisumak, Turgut, Torres-Aguila, Nuria P, Tiwari, Hemant K, Tregouet, David-Alexandre, Trompet, Stella, Tuladhar, Anil Man, Tybjaerg-Hansen, Anne, van Vugt, Marion, Vibo, Riina, Verma, Shefali S, Wiggins, Kerri L, Wennberg, Patrik, Woo, Daniel, Wilson, Peter WF, Xu, Huichun, Yang, Qiong, Yoon, Kyungheon, Lee, Jin-Moo, Cheng, Yu-Ching, Meschia, James F, Chen, Wei Min, Sale, Michele M, Zonderman, Alan B, Evans, Michele K, Wilson, James G, Correa, Adolfo, Traylor, Matthew, Lewis, Cathryn M, Carty, Cara L, Reiner, Alexander, Haessler, Jeffrey, Langefeld, Carl D, Gottesman, Rebecca F, Yaffe, Kristine, Liu, Yong Mei, Kooperberg, Charles, Lange, Leslie A, Furie, Karen L, Arnett, Donna K, Benavente, Oscar R, Grewal, Raji P, Peddareddygari, Leema Reddy, Hveem, Kristian, Lindstrom, Sara, Wang, Lu, Smith, Erin N, Gordon, William, van Hylckama Vlieg, Astrid, de Andrade, Mariza, Brody, Jennifer A, Pattee, Jack W, Brumpton, Ben M, Suchon, Pierre, Chen, Ming-Huei, Frazer, Kelly A, Turman, Constance, Germain, Marine, MacDonald, James, Braekkan, Sigrid K, Armasu, Sebastian M, Pankratz, Nathan, Jackson, Rebecca D, Nielsen, Jonas B, Giulianini, Franco, Puurunen, Marja K, Ibrahim, Manal, Heckbert, Susan R, Bammler, Theo K, McCauley, Bryan M, Taylor, Kent D, Pankow, James S, Reiner, Alexander P, Gabrielsen, Maiken E, Deleuze, Jean-Francois, O'Donnell, Chris J, Kim, Jihye, McKnight, Barbara, Kraft, Peter, Hansen, John-Bjarne, Rosendaal, Frits R, Heit, John A, Tang, Weihong, Morange, Pierre-Emmanuel, Johnson, Andrew D, Kabrhel, Christopher, van Dijk, Ewoud J, Koudstaal, Peter J, Luijckx, Gert-Jan, Nederkoorn, Paul J, van Oostenbrugge, Robert J, Visser, Marieke C, Wermer, Marieke JH, Kappelle, L Jaap, Esko, Tonu, Metspalu, Andres, Magi, Reedik, Nelis, Mari, Irvin, Marguerite R, de Leeuw, Frank-Erik, Levi, Christopher R, Maguire, Jane, Jimenez-Conde, Jordi, Sharma, Pankaj, Sudlow, Cathie LM, Rannikmae, Kristiina, Schmidt, Reinhold, Slowik, Agnieszka, Pera, Joanna, Thijs, Vincent NS, Lindgren, Arne G, Ilinca, Andreea, Melander, Olle, Engstrom, Gunnar, Rexrode, Kathryn M, Rothwell, Peter M, Stanne, Tara M, Johnson, Julie A, Danesh, John, Butterworth, Adam S, Heitsch, Laura, Boncoraglio, Giorgio B, Kubo, Michiaki, Pezzini, Alessandro, Rolfs, Arndt, Giese, Anne-Katrin, Weir, David, Ross, Owen A, Lemmons, Robin, Soderholm, Martin, Cushman, Mary, Jood, Katarina, McDonough, Caitrin W, Bell, Steven, Linkohr, Birgit, Lee, Tsong-Hai, Putaala, Jukka, Anderson, Christopher D, Lopez, Oscar L, Jian, Xueqiu, Schminke, Ulf, Cullell, Natalia, Delgado, Pilar, Ibanez, Laura, Krupinski, Jerzy, Lioutas, Vasileios, Matsuda, Koichi, Montaner, Joan, Muino, Elena, Roquer, Jaume, Sarnowski, Chloe, Sattar, Naveed, Sibolt, Gerli, Teumer, Alexander, Rutten-Jacobs, Loes, Kanai, Masahiro, Gretarsdottir, Solveig, Rost, Natalia S, Yusuf, Salim, Almgren, Peter, Ay, Hakan, Bevan, Steve, Brown, Robert D, Carrera, Caty, Buring, Julie E, Chen, Wei-Min, Cotlarciuc, Ioana, de Bakker, Paul IW, DeStefano, Anita L, den Hoed, Marcel, Duan, Qing, Engelter, Stefan T, Falcone, Guido J, Gustafsson, Stefan, Hassan, Ahamad, Holliday, Elizabeth G, Howard, George, Hsu, Fang-Chi, Ingelsson, Erik, Harris, Tamara B, Kissela, Brett M, Kleindorfer, Dawn O, Langenberg, Claudia, Lemmens, Robin, Leys, Didier, Lin, Wei-Yu, Lorentzen, Erik, Magnusson, Patrik K, McArdle, Patrick F, Pulit, Sara L, Rice, Kenneth, Sakaue, Saori, Sapkota, Bishwa R, Tanislav, Christian, Thorleifsson, Gudmar, Thorsteinsdottir, Unnur, Tzourio, Christophe, van Duijn, Cornelia M, Walters, Matthew, Wareham, Nicholas J, Amin, Najaf, Aparicio, Hugo J, Attia, John, Beiser, Alexa S, Berr, Claudine, Bustamante, Mariana, Caso, Valeria, Choi, Seung Hoan, Chowhan, Ayesha, Dartigues, Jean-Francois, Delavaran, Hossein, Dorr, Marcus, Ford, Ian, Gurpreet, Wander S, Hamsten, Anders, Hozawa, Atsushi, Ingelsson, Martin, Iwasaki, Motoki, Kaffashian, Sara, Kalra, Lalit, Kjartansson, Olafur, Kloss, Manja, Labovitz, Daniel L, Laurie, Cathy C, Li, Linxin, Lind, Lars, Lindgren, Cecilia M, Makoto, Hirata, Minegishi, Naoko, Morris, Andrew P, Muller-Nurasyid, Martina, Norrving, Bo, Ogishima, Soichi, Parati, Eugenio A, Pedersen, Nancy L, Perola, Markus, Jousilahti, Pekka, Pileggi, Silvana, Rabionet, Raquel, Riba-Llena, Iolanda, Ribases, Marta, Romero, Jose R, Rudd, Anthony G, Sarin, Antti-Pekka, Sarju, Ralhan, Satoh, Mamoru, Sawada, Norie, Sigurdsson, Asgeir, Smith, Albert, Stine, O Colin, Stott, David J, Strauch, Konstantin, Takai, Takako, Tanaka, Hideo, Touze, Emmanuel, Tsugane, Shoichiro, Uitterlinden, Andre G, Valdimarsson, Einar M, van der Lee, Sven J, Wakai, Kenji, Williams, Stephen R, Wolfe, Charles DA, Wong, Quenna, Yamaji, Taiki, Sanghera, Dharambir K, Stefansson, Kari, Martinez-Majander, Nicolas, Sobue, Kenji, Soriano-Tarraga, Carolina, Volzke, Henry, Akpa, Onoja, Sarfo, Fred S, Akpalu, Albert, Obiako, Reginald, Wahab, Kolawole, Osaigbovo, Godwin, Owolabi, Lukman, Komolafe, Morenikeji, Jenkins, Carolyn, Arulogun, Oyedunni, Ogbole, Godwin, Adeoye, Abiodun M, Akinyemi, Joshua, Agunloye, Atinuke, Fakunle, Adekunle G, Uvere, Ezinne, Olalere, Abimbola, Adebajo, Olayinka J, Chen, Junshi, Clarke, Robert, Collins, Rory, Guo, Yu, Wang, Chen, Lv, Jun, Peto, Richard, Chen, Yiping, Fairhurst-Hunter, Zammy, Hill, Michael, Pozarickij, Alfred, Schmidt, Dan, Stevens, Becky, Turnbull, Iain, Yu, Canqing, Nagai, Akiko, Murakami, Yoishinori, Shiroma, Eric J, Sigurdsson, Sigurdur, Ghanbari, Mohsen, Boerwinkle, Eric, Fongang, Bernard, Wang, Ruiqi, Ikram, Mohammad K, Volker, Uwe, de Laat, Karlijn F, van Norden, Anouk GW, de Kort, Paul L, Vermeer, Sarah E, Brouwers, Paul JAM, Gons, Rob AR, den Heijer, Tom, van Dijk, Gert W, van Rooij, Frank GW, Aamodt, Anne H, Skogholt, Anne H, Willer, Cristen J, Heuch, Ingrid, Hagen, Knut, Fritsche, Lars G, Pedersen, Linda M, Ellekjaer, Hanne, Zhou, Wei, Martinsen, Amy E, Kristoffersen, Espen S, Thomas, Laurent F, Kleinschnitz, Christoph, Frantz, Stefan, Ungethum, Kathrin, Gallego-Fabrega, Cristina, Lledos, Miquel, Llucia-Carol, Laia, Sobrino, Tomas, Campos, Francisco, Castillo, Jose, Freijo, Marimar, Arenillas, Juan Francisco, Obach, Victor, Alvarez-Sabin, Jose, Molina, Carlos A, Ribo, Marc, Munoz-Narbona, Lucia, Lopez-Cancio, Elena, Millan, Monica, Diaz-Navarro, Rosa, Vives-Bauza, Cristofol, Serrano-Heras, Gemma, Segura, Tomas, Dhar, Rajat, Delgado-Mederos, Raquel, Prats-Sanchez, Luis, Camps-Renom, Pol, Blay, Natalia, Sumoy, Lauro, Marti-Fabregas, Joan, Schnohr, Peter, Jensen, Gorm B, Benn, Marianne, Afzal, Shoaib, Kamstrup, Pia R, van Setten, Jessica, van der Laan, Sander W, Vonk, Jet MJ, Kim, Bong-Jo, Curtze, Sami, Tiainen, Marjaana, Kinnunen, Janne, Menon, Vilas, Sung, Yun Ju, Yang, Chengran, Saillour-Glenisson, Florence, Gravel, Simon, Millwood, Iona Y, Gieger, Christian, Ninomiya, Toshiharu, Grabe, Hans J, Jukema, J Wouter, Rissanen, Ina L, Strbian, Daniel, Kim, Young Jin, Chen, Pei-Hsin, Mayerhofer, Ernst, Howson, Joanna MM, Adams, Hieab, Wassertheil-Smoller, Sylvia, Christensen, Kaare, Ikram, Mohammad A, Rundek, Tatjana, Worrall, Bradford B, Lathrop, G Mark, Riaz, Moeen, Simonsick, Eleanor M, Korv, Janika, Franca, Paulo HC, Zand, Ramin, Prasad, Kameshwar, Frikke-Schmidt, Ruth, Liman, Thomas, Haeusler, Karl Georg, Ruigrok, Ynte M, Heuschmann, Peter Ulrich, Longstreth, WT, Jung, Keum Ji, Bastarache, Lisa, Pare, Guillaume, Damrauer, Scott M, Chasman, Daniel I, Rotter, Jerome I, Zwart, John-Anker, Niiranen, Teemu J, Fornage, Myriam, Liaw, Yung-Po, Seshadri, Sudha, Fernandez-Cadenas, Israel, Walters, Robin G, Ruff, Christian T, Owolabi, Mayowa O, Huffman, Jennifer E, Milani, Lili, Kamatani, Yoichiro, Dichgans, Martin, and Debette, Stephanie
Abstract: Previous genome-wide association studies (GWASs) of stroke — the second leading cause of death worldwide — were conducted predominantly in populations of European ancestry1,2. Here, in cross-ancestry GWAS meta-analyses of 110,182 patients who have had a stroke (five ancestries, 33% non-European) and 1,503,898 control individuals, we identify association signals for stroke and its subtypes at 89 (61 new) independent loci: 60 in primary inverse-variance-weighted analyses and 29 in secondary meta-regression and multitrait analyses. On the basis of internal cross-ancestry validation and an independent follow-up in 89,084 additional cases of stroke (30% non-European) and 1,013,843 control individuals, 87% of the primary stroke risk loci and 60% of the secondary stroke risk loci were replicated (P < 0.05). Effect sizes were highly correlated across ancestries. Cross-ancestry fine-mapping, in silico mutagenesis analysis3, and transcriptome-wide and proteome-wide association analyses revealed putative causal genes (such as SH3PXD2A and FURIN) and variants (such as at GRK5 and NOS3). Using a three-pronged approach4, we provide genetic evidence for putative drug effects, highlighting F11, KLKB1, PROC, GP1BA, LAMC2 and VCAM1 as possible targets, with drugs already under investigation for stroke for F11 and PROC. A polygenic score integrating cross-ancestry and ancestry-specific stroke GWASs with vascular-risk factor GWASs (integrative polygenic scores) strongly predicted ischaemic stroke in populations of European, East Asian and African ancestry5. Stroke genetic risk scores were predictive of ischaemic stroke independent of clinical risk factors in 52,600 clinical-trial participants with cardiometabolic disease. Our results provide insights to inform biology, reveal potential drug targets and derive genetic risk prediction tools across ancestries.
Published: 2022

35. Development of the ComPair gamma-ray telescope prototype

Author: Shy, Daniel, Kierans, Carolyn, Cannady, Nicolas, Caputo, Regina, Griffin, Sean, Grove, J. Eric, Hays, Elizabeth, Kong, Emily, Kirschner, Nicholas, Liceaga-Indart, Iker, McEnery, Julie, Mitchell, John, Moiseev, A. A., Parker, Lucas, Perkins, Jeremy S., Phlips, Bernard, Sasaki, Makoto, Schoenwald, Adam J., Sleator, Clio, Smith, Jacob, Smith, Lucas D., Wasti, Sambid, Woolf, Richard, Wulf, Eric, Zajczyk, Anna, Shy, Daniel, Kierans, Carolyn, Cannady, Nicolas, Caputo, Regina, Griffin, Sean, Grove, J. Eric, Hays, Elizabeth, Kong, Emily, Kirschner, Nicholas, Liceaga-Indart, Iker, McEnery, Julie, Mitchell, John, Moiseev, A. A., Parker, Lucas, Perkins, Jeremy S., Phlips, Bernard, Sasaki, Makoto, Schoenwald, Adam J., Sleator, Clio, Smith, Jacob, Smith, Lucas D., Wasti, Sambid, Woolf, Richard, Wulf, Eric, and Zajczyk, Anna
Abstract: There is a growing interest in the science uniquely enabled by observations in the MeV range, particularly in light of multi-messenger astrophysics. The Compton Pair (ComPair) telescope, a prototype of the AMEGO Probe-class concept, consists of four subsystems that together detect and characterize gamma rays in the MeV regime. A double-sided strip silicon Tracker gives a precise measure of the first Compton scatter interaction and tracks pair-conversion products. A novel cadmium zinc telluride (CZT) detector with excellent position and energy resolution beneath the Tracker detects the Compton-scattered photons. A thick cesium iodide (CsI) calorimeter contains the high-energy Compton and pair events. The instrument is surrounded by a plastic anti-coincidence (ACD) detector to veto the cosmic-ray background. In this work, we will give an overview of the science motivation and a description of the prototype development and performance.
Published: 2022
Full Text: View/download PDF

36. Stroke genetics informs drug discovery and risk prediction across ancestries

Author: Mishra, Aniket, Malik, Rainer, Hachiya, Tsuyoshi, Jürgenson, Tuuli, Namba, Shinichi, Posner, Daniel C., Kamanu, Frederick K., Koido, Masaru, Le Grand, Quentin, Shi, Mingyang, He, Yunye, Georgakis, Marios K., Caro, Ilana, Krebs, Kristi, Liaw, Yi-Ching, Vaura, Felix C., Lin, Kuang, Slagsvold Winsvold, Bendik, Srinivasasainagendra, Vinodh, Parodi, Livia, Bae, Hee-Joon, Chauhan, Ganesh, Chong, Michael R., Tomppo, Liisa, Akinyemi, Rufus, Roshchupkin, Gennady V., Habib, Naomi, Jee, Yon Ho, Thomassen, Jesper Qvist, Abedi, Vida, Cárcel-Márquez, Jara, Nygaard, Marianne, Leonard, Hampton L., Yang, Chaojie, Yonova-Doing, Ekaterina, Knol, Maria J., Lewis, Adam J., Judy, Renae L., Ago, Tetsuro, Amouyel, Philippe, Armstrong, Nicole D., Bakker, Mark K., Bartz, Traci M., Bennett, David A., Bis, Joshua C., Bordes, Constance, Børte, Sigrid, Cain, Anael, Ridker, Paul M., Cho, Kelly, Chen, Zhengming, Cruchaga, Carlos, Cole, John W., de Jager, Phil L., de Cid, Rafael, Endres, Matthias, Ferreira, Leslie E., Geerlings, Mirjam I., Gasca, Natalie C., Gudnason, Vilmundur, Hata, Jun, He, Jing, Heath, Alicia K., Ho, Yuk-Lam, Havulinna, Aki S., Hopewell, Jemma C., Hyacinth, Hyacinth I., Inouye, Michael, Jacob, Mina A., Jeon, Christina E., Jern, Christina, Kamouchi, Masahiro, Keene, Keith L., Kitazono, Takanari, Kittner, Steven J., Konuma, Takahiro, Kumar, Amit, Lacaze, Paul, Launer, Lenore J., Lee, Keon-Joo, Lepik, Kaido, Li, Jiang, Li, Liming, Manichaikul, Ani, Markus, Hugh S., Marston, Nicholas A., Meitinger, Thomas, Mitchell, Braxton D., Montellano, Felipe A., Morisaki, Takayuki, Mosley, Thomas H., Nalls, Mike A., Nordestgaard, Børge G., O'Donnell, Martin J., Okada, Yukinori, Onland-Moret, N. Charlotte, Ovbiagele, Bruce, Peters, Annette, Psaty, Bruce M., Rich, Stephen S., Rosand, Jonathan, Sabatine, Marc S., Sacco, Ralph L., Saleheen, Danish, Sandset, Else Charlotte, Salomaa, Veikko, Sargurupremraj, Muralidharan, Sasaki, Makoto, Satizabal, Claudia L., Schmidt, Carsten O., Shimizu, Atsushi, Smith, Nicholas L., Sloane, Kelly L., Sutoh, Yoichi, Sun, Yan V., Tanno, Kozo, Tiedt, Steffen, Tatlisumak, Turgut, Torres-Aguila, Nuria P., Tiwari, Hemant K., Trégouët, David-Alexandre, Trompet, Stella, Tuladhar, Anil Man, Tybjærg-Hansen, Anne, van Vugt, Marion, Vibo, Riina, Verma, Shefali S., Wiggins, Kerri L., Wennberg, Patrik, Woo, Daniel, Wilson, Peter W. F., Xu, Huichun, Yang, Qiong, Yoon, Kyungheon, Millwood, Iona Y., Gieger, Christian, Ninomiya, Toshiharu, Grabe, Hans J., Jukema, J. Wouter, Rissanen, Ina L., Strbian, Daniel, Kim, Young Jin, Chen, Pei-Hsin, Mayerhofer, Ernst, Howson, Joanna M. M., Irvin, Marguerite R., Adams, Hieab, Wassertheil-Smoller, Sylvia, Christensen, Kaare, Ikram, Mohammad A., Rundek, Tatjana, Worrall, Bradford B., Lathrop, G. Mark, Riaz, Moeen, Simonsick, Eleanor M., Kõrv, Janika, França, Paulo H. C., Zand, Ramin, Prasad, Kameshwar, Frikke-Schmidt, Ruth, de Leeuw, Frank-Erik, Liman, Thomas, Haeusler, Karl Georg, Ruigrok, Ynte M., Heuschmann, Peter Ulrich, Longstreth, W. T., Jung, Keum Ji, Bastarache, Lisa, Paré, Guillaume, Damrauer, Scott M., Chasman, Daniel I., Rotter, Jerome I., Anderson, Christopher D., Zwart, John-Anker, Niiranen, Teemu J., Fornage, Myriam, Liaw, Yung-Po, Seshadri, Sudha, Fernández-Cadenas, Israel, Walters, Robin G., Ruff, Christian T., Owolabi, Mayowa O., Huffman, Jennifer E., Milani, Lili, Kamatani, Yoichiro, Dichgans, Martin, Debette, Stephanie, Mishra, Aniket, Malik, Rainer, Hachiya, Tsuyoshi, Jürgenson, Tuuli, Namba, Shinichi, Posner, Daniel C., Kamanu, Frederick K., Koido, Masaru, Le Grand, Quentin, Shi, Mingyang, He, Yunye, Georgakis, Marios K., Caro, Ilana, Krebs, Kristi, Liaw, Yi-Ching, Vaura, Felix C., Lin, Kuang, Slagsvold Winsvold, Bendik, Srinivasasainagendra, Vinodh, Parodi, Livia, Bae, Hee-Joon, Chauhan, Ganesh, Chong, Michael R., Tomppo, Liisa, Akinyemi, Rufus, Roshchupkin, Gennady V., Habib, Naomi, Jee, Yon Ho, Thomassen, Jesper Qvist, Abedi, Vida, Cárcel-Márquez, Jara, Nygaard, Marianne, Leonard, Hampton L., Yang, Chaojie, Yonova-Doing, Ekaterina, Knol, Maria J., Lewis, Adam J., Judy, Renae L., Ago, Tetsuro, Amouyel, Philippe, Armstrong, Nicole D., Bakker, Mark K., Bartz, Traci M., Bennett, David A., Bis, Joshua C., Bordes, Constance, Børte, Sigrid, Cain, Anael, Ridker, Paul M., Cho, Kelly, Chen, Zhengming, Cruchaga, Carlos, Cole, John W., de Jager, Phil L., de Cid, Rafael, Endres, Matthias, Ferreira, Leslie E., Geerlings, Mirjam I., Gasca, Natalie C., Gudnason, Vilmundur, Hata, Jun, He, Jing, Heath, Alicia K., Ho, Yuk-Lam, Havulinna, Aki S., Hopewell, Jemma C., Hyacinth, Hyacinth I., Inouye, Michael, Jacob, Mina A., Jeon, Christina E., Jern, Christina, Kamouchi, Masahiro, Keene, Keith L., Kitazono, Takanari, Kittner, Steven J., Konuma, Takahiro, Kumar, Amit, Lacaze, Paul, Launer, Lenore J., Lee, Keon-Joo, Lepik, Kaido, Li, Jiang, Li, Liming, Manichaikul, Ani, Markus, Hugh S., Marston, Nicholas A., Meitinger, Thomas, Mitchell, Braxton D., Montellano, Felipe A., Morisaki, Takayuki, Mosley, Thomas H., Nalls, Mike A., Nordestgaard, Børge G., O'Donnell, Martin J., Okada, Yukinori, Onland-Moret, N. Charlotte, Ovbiagele, Bruce, Peters, Annette, Psaty, Bruce M., Rich, Stephen S., Rosand, Jonathan, Sabatine, Marc S., Sacco, Ralph L., Saleheen, Danish, Sandset, Else Charlotte, Salomaa, Veikko, Sargurupremraj, Muralidharan, Sasaki, Makoto, Satizabal, Claudia L., Schmidt, Carsten O., Shimizu, Atsushi, Smith, Nicholas L., Sloane, Kelly L., Sutoh, Yoichi, Sun, Yan V., Tanno, Kozo, Tiedt, Steffen, Tatlisumak, Turgut, Torres-Aguila, Nuria P., Tiwari, Hemant K., Trégouët, David-Alexandre, Trompet, Stella, Tuladhar, Anil Man, Tybjærg-Hansen, Anne, van Vugt, Marion, Vibo, Riina, Verma, Shefali S., Wiggins, Kerri L., Wennberg, Patrik, Woo, Daniel, Wilson, Peter W. F., Xu, Huichun, Yang, Qiong, Yoon, Kyungheon, Millwood, Iona Y., Gieger, Christian, Ninomiya, Toshiharu, Grabe, Hans J., Jukema, J. Wouter, Rissanen, Ina L., Strbian, Daniel, Kim, Young Jin, Chen, Pei-Hsin, Mayerhofer, Ernst, Howson, Joanna M. M., Irvin, Marguerite R., Adams, Hieab, Wassertheil-Smoller, Sylvia, Christensen, Kaare, Ikram, Mohammad A., Rundek, Tatjana, Worrall, Bradford B., Lathrop, G. Mark, Riaz, Moeen, Simonsick, Eleanor M., Kõrv, Janika, França, Paulo H. C., Zand, Ramin, Prasad, Kameshwar, Frikke-Schmidt, Ruth, de Leeuw, Frank-Erik, Liman, Thomas, Haeusler, Karl Georg, Ruigrok, Ynte M., Heuschmann, Peter Ulrich, Longstreth, W. T., Jung, Keum Ji, Bastarache, Lisa, Paré, Guillaume, Damrauer, Scott M., Chasman, Daniel I., Rotter, Jerome I., Anderson, Christopher D., Zwart, John-Anker, Niiranen, Teemu J., Fornage, Myriam, Liaw, Yung-Po, Seshadri, Sudha, Fernández-Cadenas, Israel, Walters, Robin G., Ruff, Christian T., Owolabi, Mayowa O., Huffman, Jennifer E., Milani, Lili, Kamatani, Yoichiro, Dichgans, Martin, and Debette, Stephanie
Abstract: Previous genome-wide association studies (GWASs) of stroke - the second leading cause of death worldwide - were conducted predominantly in populations of European ancestry1,2. Here, in cross-ancestry GWAS meta-analyses of 110,182 patients who have had a stroke (five ancestries, 33% non-European) and 1,503,898 control individuals, we identify association signals for stroke and its subtypes at 89 (61 new) independent loci: 60 in primary inverse-variance-weighted analyses and 29 in secondary meta-regression and multitrait analyses. On the basis of internal cross-ancestry validation and an independent follow-up in 89,084 additional cases of stroke (30% non-European) and 1,013,843 control individuals, 87% of the primary stroke risk loci and 60% of the secondary stroke risk loci were replicated (P < 0.05). Effect sizes were highly correlated across ancestries. Cross-ancestry fine-mapping, in silico mutagenesis analysis3, and transcriptome-wide and proteome-wide association analyses revealed putative causal genes (such as SH3PXD2A and FURIN) and variants (such as at GRK5 and NOS3). Using a three-pronged approach4, we provide genetic evidence for putative drug effects, highlighting F11, KLKB1, PROC, GP1BA, LAMC2 and VCAM1 as possible targets, with drugs already under investigation for stroke for F11 and PROC. A polygenic score integrating cross-ancestry and ancestry-specific stroke GWASs with vascular-risk factor GWASs (integrative polygenic scores) strongly predicted ischaemic stroke in populations of European, East Asian and African ancestry5. Stroke genetic risk scores were predictive of ischaemic stroke independent of clinical risk factors in 52,600 clinical-trial participants with cardiometabolic disease. Our results provide insights to inform biology, reveal potential drug targets and derive genetic risk prediction tools across ancestries., Publisher correction: Mishra, A., Malik, R., Hachiya, T. et al. Publisher Correction: Stroke genetics informs drug discovery and risk prediction across ancestries. Nature 612, E7 (2022). DOI: 10.1038/s41586-022-05492-5
Published: 2022
Full Text: View/download PDF

37. Stroke genetics informs drug discovery and risk prediction across ancestries

Author: Mishra, Aniket, Malik, Rainer, Hachiya, Tsuyoshi, Jürgenson, Tuuli, Namba, Shinichi, Posner, Daniel C., Kamanu, Frederick K., Koido, Masaru, Le Grand, Quentin, Shi, Mingyang, He, Yunye, Georgakis, Marios K., Caro, Ilana, Krebs, Kristi, Liaw, Yi-Ching, Vaura, Felix C., Lin, Kuang, Slagsvold Winsvold, Bendik, Srinivasasainagendra, Vinodh, Parodi, Livia, Bae, Hee-Joon, Chauhan, Ganesh, Chong, Michael R., Tomppo, Liisa, Akinyemi, Rufus, Roshchupkin, Gennady V., Habib, Naomi, Jee, Yon Ho, Thomassen, Jesper Qvist, Abedi, Vida, Cárcel-Márquez, Jara, Nygaard, Marianne, Leonard, Hampton L., Yang, Chaojie, Yonova-Doing, Ekaterina, Knol, Maria J., Lewis, Adam J., Judy, Renae L., Ago, Tetsuro, Amouyel, Philippe, Armstrong, Nicole D., Bakker, Mark K., Bartz, Traci M., Bennett, David A., Bis, Joshua C., Bordes, Constance, Børte, Sigrid, Cain, Anael, Ridker, Paul M., Cho, Kelly, Chen, Zhengming, Cruchaga, Carlos, Cole, John W., de Jager, Phil L., de Cid, Rafael, Endres, Matthias, Ferreira, Leslie E., Geerlings, Mirjam I., Gasca, Natalie C., Gudnason, Vilmundur, Hata, Jun, He, Jing, Heath, Alicia K., Ho, Yuk-Lam, Havulinna, Aki S., Hopewell, Jemma C., Hyacinth, Hyacinth I., Inouye, Michael, Jacob, Mina A., Jeon, Christina E., Jern, Christina, Kamouchi, Masahiro, Keene, Keith L., Kitazono, Takanari, Kittner, Steven J., Konuma, Takahiro, Kumar, Amit, Lacaze, Paul, Launer, Lenore J., Lee, Keon-Joo, Lepik, Kaido, Li, Jiang, Li, Liming, Manichaikul, Ani, Markus, Hugh S., Marston, Nicholas A., Meitinger, Thomas, Mitchell, Braxton D., Montellano, Felipe A., Morisaki, Takayuki, Mosley, Thomas H., Nalls, Mike A., Nordestgaard, Børge G., O'Donnell, Martin J., Okada, Yukinori, Onland-Moret, N. Charlotte, Ovbiagele, Bruce, Peters, Annette, Psaty, Bruce M., Rich, Stephen S., Rosand, Jonathan, Sabatine, Marc S., Sacco, Ralph L., Saleheen, Danish, Sandset, Else Charlotte, Salomaa, Veikko, Sargurupremraj, Muralidharan, Sasaki, Makoto, Satizabal, Claudia L., Schmidt, Carsten O., Shimizu, Atsushi, Smith, Nicholas L., Sloane, Kelly L., Sutoh, Yoichi, Sun, Yan V., Tanno, Kozo, Tiedt, Steffen, Tatlisumak, Turgut, Torres-Aguila, Nuria P., Tiwari, Hemant K., Trégouët, David-Alexandre, Trompet, Stella, Tuladhar, Anil Man, Tybjærg-Hansen, Anne, van Vugt, Marion, Vibo, Riina, Verma, Shefali S., Wiggins, Kerri L., Wennberg, Patrik, Woo, Daniel, Wilson, Peter W. F., Xu, Huichun, Yang, Qiong, Yoon, Kyungheon, Millwood, Iona Y., Gieger, Christian, Ninomiya, Toshiharu, Grabe, Hans J., Jukema, J. Wouter, Rissanen, Ina L., Strbian, Daniel, Kim, Young Jin, Chen, Pei-Hsin, Mayerhofer, Ernst, Howson, Joanna M. M., Irvin, Marguerite R., Adams, Hieab, Wassertheil-Smoller, Sylvia, Christensen, Kaare, Ikram, Mohammad A., Rundek, Tatjana, Worrall, Bradford B., Lathrop, G. Mark, Riaz, Moeen, Simonsick, Eleanor M., Kõrv, Janika, França, Paulo H. C., Zand, Ramin, Prasad, Kameshwar, Frikke-Schmidt, Ruth, de Leeuw, Frank-Erik, Liman, Thomas, Haeusler, Karl Georg, Ruigrok, Ynte M., Heuschmann, Peter Ulrich, Longstreth, W. T., Jung, Keum Ji, Bastarache, Lisa, Paré, Guillaume, Damrauer, Scott M., Chasman, Daniel I., Rotter, Jerome I., Anderson, Christopher D., Zwart, John-Anker, Niiranen, Teemu J., Fornage, Myriam, Liaw, Yung-Po, Seshadri, Sudha, Fernández-Cadenas, Israel, Walters, Robin G., Ruff, Christian T., Owolabi, Mayowa O., Huffman, Jennifer E., Milani, Lili, Kamatani, Yoichiro, Dichgans, Martin, Debette, Stephanie, Mishra, Aniket, Malik, Rainer, Hachiya, Tsuyoshi, Jürgenson, Tuuli, Namba, Shinichi, Posner, Daniel C., Kamanu, Frederick K., Koido, Masaru, Le Grand, Quentin, Shi, Mingyang, He, Yunye, Georgakis, Marios K., Caro, Ilana, Krebs, Kristi, Liaw, Yi-Ching, Vaura, Felix C., Lin, Kuang, Slagsvold Winsvold, Bendik, Srinivasasainagendra, Vinodh, Parodi, Livia, Bae, Hee-Joon, Chauhan, Ganesh, Chong, Michael R., Tomppo, Liisa, Akinyemi, Rufus, Roshchupkin, Gennady V., Habib, Naomi, Jee, Yon Ho, Thomassen, Jesper Qvist, Abedi, Vida, Cárcel-Márquez, Jara, Nygaard, Marianne, Leonard, Hampton L., Yang, Chaojie, Yonova-Doing, Ekaterina, Knol, Maria J., Lewis, Adam J., Judy, Renae L., Ago, Tetsuro, Amouyel, Philippe, Armstrong, Nicole D., Bakker, Mark K., Bartz, Traci M., Bennett, David A., Bis, Joshua C., Bordes, Constance, Børte, Sigrid, Cain, Anael, Ridker, Paul M., Cho, Kelly, Chen, Zhengming, Cruchaga, Carlos, Cole, John W., de Jager, Phil L., de Cid, Rafael, Endres, Matthias, Ferreira, Leslie E., Geerlings, Mirjam I., Gasca, Natalie C., Gudnason, Vilmundur, Hata, Jun, He, Jing, Heath, Alicia K., Ho, Yuk-Lam, Havulinna, Aki S., Hopewell, Jemma C., Hyacinth, Hyacinth I., Inouye, Michael, Jacob, Mina A., Jeon, Christina E., Jern, Christina, Kamouchi, Masahiro, Keene, Keith L., Kitazono, Takanari, Kittner, Steven J., Konuma, Takahiro, Kumar, Amit, Lacaze, Paul, Launer, Lenore J., Lee, Keon-Joo, Lepik, Kaido, Li, Jiang, Li, Liming, Manichaikul, Ani, Markus, Hugh S., Marston, Nicholas A., Meitinger, Thomas, Mitchell, Braxton D., Montellano, Felipe A., Morisaki, Takayuki, Mosley, Thomas H., Nalls, Mike A., Nordestgaard, Børge G., O'Donnell, Martin J., Okada, Yukinori, Onland-Moret, N. Charlotte, Ovbiagele, Bruce, Peters, Annette, Psaty, Bruce M., Rich, Stephen S., Rosand, Jonathan, Sabatine, Marc S., Sacco, Ralph L., Saleheen, Danish, Sandset, Else Charlotte, Salomaa, Veikko, Sargurupremraj, Muralidharan, Sasaki, Makoto, Satizabal, Claudia L., Schmidt, Carsten O., Shimizu, Atsushi, Smith, Nicholas L., Sloane, Kelly L., Sutoh, Yoichi, Sun, Yan V., Tanno, Kozo, Tiedt, Steffen, Tatlisumak, Turgut, Torres-Aguila, Nuria P., Tiwari, Hemant K., Trégouët, David-Alexandre, Trompet, Stella, Tuladhar, Anil Man, Tybjærg-Hansen, Anne, van Vugt, Marion, Vibo, Riina, Verma, Shefali S., Wiggins, Kerri L., Wennberg, Patrik, Woo, Daniel, Wilson, Peter W. F., Xu, Huichun, Yang, Qiong, Yoon, Kyungheon, Millwood, Iona Y., Gieger, Christian, Ninomiya, Toshiharu, Grabe, Hans J., Jukema, J. Wouter, Rissanen, Ina L., Strbian, Daniel, Kim, Young Jin, Chen, Pei-Hsin, Mayerhofer, Ernst, Howson, Joanna M. M., Irvin, Marguerite R., Adams, Hieab, Wassertheil-Smoller, Sylvia, Christensen, Kaare, Ikram, Mohammad A., Rundek, Tatjana, Worrall, Bradford B., Lathrop, G. Mark, Riaz, Moeen, Simonsick, Eleanor M., Kõrv, Janika, França, Paulo H. C., Zand, Ramin, Prasad, Kameshwar, Frikke-Schmidt, Ruth, de Leeuw, Frank-Erik, Liman, Thomas, Haeusler, Karl Georg, Ruigrok, Ynte M., Heuschmann, Peter Ulrich, Longstreth, W. T., Jung, Keum Ji, Bastarache, Lisa, Paré, Guillaume, Damrauer, Scott M., Chasman, Daniel I., Rotter, Jerome I., Anderson, Christopher D., Zwart, John-Anker, Niiranen, Teemu J., Fornage, Myriam, Liaw, Yung-Po, Seshadri, Sudha, Fernández-Cadenas, Israel, Walters, Robin G., Ruff, Christian T., Owolabi, Mayowa O., Huffman, Jennifer E., Milani, Lili, Kamatani, Yoichiro, Dichgans, Martin, and Debette, Stephanie
Abstract: Previous genome-wide association studies (GWASs) of stroke - the second leading cause of death worldwide - were conducted predominantly in populations of European ancestry1,2. Here, in cross-ancestry GWAS meta-analyses of 110,182 patients who have had a stroke (five ancestries, 33% non-European) and 1,503,898 control individuals, we identify association signals for stroke and its subtypes at 89 (61 new) independent loci: 60 in primary inverse-variance-weighted analyses and 29 in secondary meta-regression and multitrait analyses. On the basis of internal cross-ancestry validation and an independent follow-up in 89,084 additional cases of stroke (30% non-European) and 1,013,843 control individuals, 87% of the primary stroke risk loci and 60% of the secondary stroke risk loci were replicated (P < 0.05). Effect sizes were highly correlated across ancestries. Cross-ancestry fine-mapping, in silico mutagenesis analysis3, and transcriptome-wide and proteome-wide association analyses revealed putative causal genes (such as SH3PXD2A and FURIN) and variants (such as at GRK5 and NOS3). Using a three-pronged approach4, we provide genetic evidence for putative drug effects, highlighting F11, KLKB1, PROC, GP1BA, LAMC2 and VCAM1 as possible targets, with drugs already under investigation for stroke for F11 and PROC. A polygenic score integrating cross-ancestry and ancestry-specific stroke GWASs with vascular-risk factor GWASs (integrative polygenic scores) strongly predicted ischaemic stroke in populations of European, East Asian and African ancestry5. Stroke genetic risk scores were predictive of ischaemic stroke independent of clinical risk factors in 52,600 clinical-trial participants with cardiometabolic disease. Our results provide insights to inform biology, reveal potential drug targets and derive genetic risk prediction tools across ancestries., Publisher correction: Mishra, A., Malik, R., Hachiya, T. et al. Publisher Correction: Stroke genetics informs drug discovery and risk prediction across ancestries. Nature 612, E7 (2022). DOI: 10.1038/s41586-022-05492-5
Published: 2022
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38. Exploring the MeV Sky with a Combined Coded Mask and Compton Telescope: The Galactic Explorer with a Coded Aperture Mask Compton Telescope (GECCO)

Author: Orlando, Elena, Bottacini, Eugenio, Moiseev, Alexander, Bodaghee, Arash, Collmar, Werner, Ensslin, Torsten, Moskalenko, Igor V., Negro, Michela, Profumo, Stefano, Baring, Matthew G., Bolotnikov, Aleksey, Cannady, Nicholas, Carini, Gabriella A., Digel, Seth, Grenier, Isabelle A., Harding, Alice K., Hartmann, Dieter, Herrmann, Sven, Kerr, Matthew, Krivonos, Roman, Laurent, Philippe, Longo, Francesco, Morselli, Aldo, Sasaki, Makoto, Shawhan, Peter, Skinner, Gerry, Smith, Lucas D., Stecker, Floyd W., Strong, Andrew, Sturner, Steven, Thompson, David J., Tomsick, John A., Wadiasingh, Zorawar, Woolf, Richard S., Yates, Eric, Zoglauer, Andreas, Orlando, Elena, Bottacini, Eugenio, Moiseev, Alexander, Bodaghee, Arash, Collmar, Werner, Ensslin, Torsten, Moskalenko, Igor V., Negro, Michela, Profumo, Stefano, Baring, Matthew G., Bolotnikov, Aleksey, Cannady, Nicholas, Carini, Gabriella A., Digel, Seth, Grenier, Isabelle A., Harding, Alice K., Hartmann, Dieter, Herrmann, Sven, Kerr, Matthew, Krivonos, Roman, Laurent, Philippe, Longo, Francesco, Morselli, Aldo, Sasaki, Makoto, Shawhan, Peter, Skinner, Gerry, Smith, Lucas D., Stecker, Floyd W., Strong, Andrew, Sturner, Steven, Thompson, David J., Tomsick, John A., Wadiasingh, Zorawar, Woolf, Richard S., Yates, Eric, and Zoglauer, Andreas
Abstract: The sky at MeV energies is currently poorly explored. Here we present an innovative mission concept and we outline the scientific motivation for combining a coded mask and a Compton telescope. The Galactic Explorer with a Coded Aperture Mask Compton Telescope (GECCO) is a novel concept for a next-generation telescope covering hard X-ray and soft gamma-ray energies. The potential and importance of this approach that will bridge the observational gap in the MeV energy range are presented. With the unprecedented angular resolution of the coded mask telescope combined with the sensitive Compton telescope, a mission such as GECCO will finally disentangle the discrete sources from the truly diffuse emission, unveiling the origin of the gamma-ray Galactic center excess and the Fermi Bubbles, and uncovering properties of low-energy cosmic rays, and their propagation in the Galaxy. Individual Galactic and extragalactic sources will be detected, which will also allow studies of source populations. Nuclear and annihilation lines will be spatially and spectrally resolved from the continuum emission and from sources, addressing the role of low-energy cosmic rays in star formation and galaxy evolution, the origin of the 511 keV positron line, fundamental physics, and the chemical enrichment in the Galaxy. It will also detect explosive transient gamma-ray sources, which will enable identifying and studying the astrophysical objects that produce gravitational waves and neutrinos in a multi-messenger context. A GECCO mission will provide essential contributions to the areas "New Messengers and New Physics" and "Unveiling the Drivers of Galaxy Growth" emphasized in the Decadal Report on Astronomy and Astrophysics 2020., Comment: 16 pages. Contact authors: Elena Orlando, Eugenio Bottacini
Published: 2021

39. Definition of the profile gain factor and its application for internal transport barrier analysis in torus plasmas

Author: Kobayashi, Tatsuya, TAKAHASHI, Hiromi, NAGAOKA, Kenichi, Sasaki, Makoto, YOKOYAMA, Masayuki, SEKI, Ryosuke, YOSHINUMA, Mikiro, IDA, Katsumi, LHD, Experiment Group, Kobayashi, Tatsuya, TAKAHASHI, Hiromi, NAGAOKA, Kenichi, Sasaki, Makoto, YOKOYAMA, Masayuki, SEKI, Ryosuke, YOSHINUMA, Mikiro, IDA, Katsumi, and LHD, Experiment Group
Abstract: In this paper, a new criterion for the internal transport barrier (ITB) formation is proposed by defining a unique scalar parameter, the profile gain factor. The profile gain factor shows degree of the confinement improvement with respect to an arbitrary reference temperature profile in the L-mode. As the reference L-mode profile for the large helical device (LHD), the edge ion temperature profile data is extrapolated to the core by the L-mode profile function, which is characterized by the thermal diffusion coefficient being proportional to the local ion temperature. The profile gain factor is defined as the ratio of the ion stored energy experimentally measured to that evaluated from the reference L-mode profile. The proposed method is applied to the LHD experimental data, and its capability for quantification of the ITB strength is demonstrated., source:T Kobayashi et al 2019 Plasma Phys. Control. Fusion 61 085005, source:https://doi.org/10.1088/1361-6587/ab221c, identifier:0000-0001-5669-1937
Published: 2021

40. Method for estimating the frequency-wavenumber resolved power spectrum density using the maximum entropy method for limited spatial points

Author: Kobayashi, Tatsuya, Nishizawa, Takashi, Sasaki, Makoto, YOSHINUMA, Mikiro, IDA, Katsumi, Kobayashi, Tatsuya, Nishizawa, Takashi, Sasaki, Makoto, YOSHINUMA, Mikiro, and IDA, Katsumi
Abstract: A combination of the Fourier transform and the maximum entropy method for estimating the frequency-wavenumber resolved power spectrum density is proposed. After illustrating the physical insight of the maximum entropy method by using synthetic test data, capability of the proposed method is tested using numerical simulation data. The method is also applied to experimental data obtained by the beam emission spectroscopy in the Large Helical Device. All of those examinations show that the proposed method provides more plausible results than conventional methods when the available spatial points are limited., source:T Kobayashi et al 2021 Plasma Phys. Control. Fusion 63 045011, source:https://doi.org/10.1088/1361-6587/abe024, identifier:0000-0001-6835-1569, identifier:0000-0001-5669-1937, identifier:0000-0002-0585-4561, identifier:0000-0003-1804-2308
Published: 2021

41. Impact of helium neutral gas puff on plasma turbulence in linear magnetized argon plasmas

Author: Kobayashi, Tatsuya, KIN, F., Kawachi, Y., Sasaki, Makoto, Kosuga, Yusuke, Yamasaki, K., INAGAKI, Sigeru, Kobayashi, Tatsuya, KIN, F., Kawachi, Y., Sasaki, Makoto, Kosuga, Yusuke, Yamasaki, K., and INAGAKI, Sigeru
Abstract: In order to explore the impact of the neutrals on the plasma turbulence, a new gas puff system is developed for a linear magnetized plasma column PANTA. Helium gas is injected into the argon plasma without changing the electron density profile. After the helium gas puff, the dominant fluctuation mode changes from the broadband m = 2 drift wave to the coherent m = 1 mode, where m is the azimuthal mode number. Accordingly, the property of the nonlinear coupling with other fluctuating modes changes from broadband couplings to coherent couplings., source:Phys. Plasmas 27, 062309 (2020), source:https://doi.org/10.1063/5.0007899, identifier:0000-0001-5669-1937
Published: 2021

42. Body mass index and colorectal cancer risk : A Mendelian randomization study

Author: Suzuki, Shiori, Goto, Atsushi, Nakatochi, Masahiro, Narita, Akira, Yamaji, Taiki, Sawada, Norie, Katagiri, Ryoko, Iwagami, Masao, Hanyuda, Akiko, Hachiya, Tsuyoshi, Sutoh, Yoichi, Oze, Isao, Koyanagi, Yuriko N., Kasugai, Yumiko, Taniyama, Yukari, Ito, Hidemi, Ikezaki, Hiroaki, Nishida, Yuichiro, Tamura, Takashi, Mikami, Haruo, Takezaki, Toshiro, Suzuki, Sadao, Ozaki, Etsuko, Kuriki, Kiyonori, Takashima, Naoyuki, Arisawa, Kokichi, Takeuchi, Kenji, Tanno, Kozo, Shimizu, Atsushi, Tamiya, Gen, Hozawa, Atsushi, Kinoshita, Kengo, Wakai, Kenji, Sasaki, Makoto, Yamamoto, Masayuki, Matsuo, Keitaro, Tsugane, Shoichiro, Iwasaki, Motoki, Suzuki, Shiori, Goto, Atsushi, Nakatochi, Masahiro, Narita, Akira, Yamaji, Taiki, Sawada, Norie, Katagiri, Ryoko, Iwagami, Masao, Hanyuda, Akiko, Hachiya, Tsuyoshi, Sutoh, Yoichi, Oze, Isao, Koyanagi, Yuriko N., Kasugai, Yumiko, Taniyama, Yukari, Ito, Hidemi, Ikezaki, Hiroaki, Nishida, Yuichiro, Tamura, Takashi, Mikami, Haruo, Takezaki, Toshiro, Suzuki, Sadao, Ozaki, Etsuko, Kuriki, Kiyonori, Takashima, Naoyuki, Arisawa, Kokichi, Takeuchi, Kenji, Tanno, Kozo, Shimizu, Atsushi, Tamiya, Gen, Hozawa, Atsushi, Kinoshita, Kengo, Wakai, Kenji, Sasaki, Makoto, Yamamoto, Masayuki, Matsuo, Keitaro, Tsugane, Shoichiro, and Iwasaki, Motoki
Abstract: Traditional observational studies have reported a positive association between higher body mass index (BMI) and the risk of colorectal cancer (CRC). However, evidence from other approaches to pursue the causal relationship between BMI and CRC is sparse. A two-sample Mendelian randomization (MR) study was undertaken using 68 single nucleotide polymorphisms (SNPs) from the Japanese genome-wide association study (GWAS) and 654 SNPs from the GWAS catalogue for BMI as sets of instrumental variables. For the analysis of SNP-BMI associations, we undertook a meta-analysis with 36 303 participants in the Japanese Consortium of Genetic Epidemiology studies (J-CGE), comprising normal populations. For the analysis of SNP-CRC associations, we utilized 7636 CRC cases and 37 141 controls from five studies in Japan, and undertook a meta-analysis. Mendelian randomization analysis of inverse-variance weighted method indicated that a one-unit (kg/m2) increase in genetically predicted BMI was associated with an odds ratio of 1.13 (95% confidence interval, 1.06-1.20; P value <.001) for CRC using the set of 68 SNPs, and an odds ratio of 1.07 (1.03-1.11, 0.001) for CRC using the set of 654 SNPs. Sensitivity analyses robustly showed increased odds ratios for CRC for every one-unit increase in genetically predicted BMI. Our MR analyses strongly support the evidence that higher BMI influences the risk of CRC. Although Asians are generally leaner than Europeans and North Americans, avoiding higher BMI seems to be important for the prevention of CRC in Asian populations.
Published: 2021

43. Calibration of Setting of Mach Probes by Observing GAM Oscillations

Author: ITOH, Kimitaka, ZHAO, Kaijun, DONG, Jiaqi, ITOH, Sanae -I., FUJISAWA, Akihide, INAGAKI, Shigeru, Sasaki, Makoto, NAGASHIMA, Yoshihiko, Kosuga, Yusuke, CHENG, Jun, Kobayashi, Tatsuya, ITOH, Kimitaka, ZHAO, Kaijun, DONG, Jiaqi, ITOH, Sanae -I., FUJISAWA, Akihide, INAGAKI, Shigeru, Sasaki, Makoto, NAGASHIMA, Yoshihiko, Kosuga, Yusuke, CHENG, Jun, and Kobayashi, Tatsuya
Abstract: The influence of relative displacement of Mach probe (which is placed near the top of magnetic surface) on the interference of signals is discussed. An error can arise in measured value of poloidal electric field. The Mach number perturbation at the GAM frequency has an interference from the density perturbation. The interference from the density perturbation can propagate to all of Mach number measurement. By observing the signals associated with GAM oscillations, the error in setting the probe arrays can be detected. This result can be applied to correct the positioning of probes., source:https://doi.org/10.1585/pfr.11.1402002, identifier:0000-0003-3873-4766
Published: 2021

44. Frequency and plasma condition dependent spatial structure of low frequency global potential oscillations in the TJ-II stellarator

Author: Kobayashi, Tatsuya, Losada, U., Liu, B., Esreada, T., Milligen, B.Ph. van, Gerru, R., Sasaki, Makoto, Hidalgo, C., Kobayashi, Tatsuya, Losada, U., Liu, B., Esreada, T., Milligen, B.Ph. van, Gerru, R., Sasaki, Makoto, and Hidalgo, C.
Abstract: In this letter, we investigate the spatial structure of a low frequency global potential oscillation, which is likely ascribed as the low frequency zonal flows, in TJ-II laboratory plasmas. In two plasmas produced by different heating schemes (electron cyclotron resonance heating and neutral beam injection heating) and characterized by different mean radial electric field structures, frequency-space-decomposed spectra of the global potential oscillation are obtained. In both cases, the oscillatory field has a single-peaked potential structure and a dipole radial electric field structure. The oscillating structure depends on its frequency as well as on the heating scheme., source:Citation T. Kobayashi et al 2019 Nucl. Fusion 59 044006, source:https://doi.org/10.1088/1741-4326/ab0122, identifier:0000-0001-5669-1937
Published: 2021

45. Azimuthal inhomogeneity of turbulence structure and its impact on intermittent particle transport in linear magnetized plasmas

Author: Kobayashi, Tatsuya, INAGAKI, Shigeru, Sasaki, Makoto, Kobayashi, Tatsuya, INAGAKI, Shigeru, and Sasaki, Makoto
Abstract: Fluctuation component in the turbulence regime is found to be azimuthally localized at a phase of the global coherent modes in a linear magnetized plasma PANTA. Spatial distribution of squared bicoherence is given in the azimuthal cross section as an indicator of nonlinear energy transfer function from the global coherent mode to the turbulence. Squared bicoherence is strong at a phase where the turbulence amplitude is large. As a result of the turbulence localization, time evolution of radial particle flux becomes bursty. Statistical features such as skewness and kurtosis are strongly modified by the localized turbulence component, although contribution to mean particle flux profile is small., source:Physics of Plasmas 22, 112301 (2015); https://doi.org/10.1063/1.4934537, source:https://doi.org/10.1063/1.4934537, identifier:0000-0001-5669-1937
Published: 2021

46. Structure formation in parallel ion flow and density profiles by cross-ferroic turbulent transport in linear magnetized plasma

Author: Kobayashi, Tatsuya, INAGAKI, Shigeru, Kosuga, Yusuke, Sasaki, Makoto, NAGASHIMA, Yoshihiko, Yamada, T., Arakawa, H., KASUYA, Naohiro, Fujisawa, N., ITOH, Sanae -I., ITOH, Kimitaka, Kobayashi, Tatsuya, INAGAKI, Shigeru, Kosuga, Yusuke, Sasaki, Makoto, NAGASHIMA, Yoshihiko, Yamada, T., Arakawa, H., KASUYA, Naohiro, Fujisawa, N., ITOH, Sanae -I., and ITOH, Kimitaka
Abstract: In this paper, we show the direct observation of the parallel flow structure and the parallel Reynolds stress in a linear magnetized plasma, in which a cross-ferroic turbulence system is formed [Inagaki et al., Sci. Rep. 6, 22189 (2016)]. It is shown that the parallel Reynolds stress induced by the density gradient driven drift wave is the source of the parallel flow structure. Moreover, the generated parallel flow shear by the parallel Reynolds stress is found to drive the parallel flow shear driven instability D'Angelo mode, which coexists with the original drift wave. The excited D'Angelo mode induces the inward particle flux, which seems to help in maintaining the peaked density profile., source:Physics of Plasmas 23, 102311 (2016); https://doi.org/10.1063/1.4965915, source:https://doi.org/10.1063/1.4965915, identifier:0000-0001-5669-1937
Published: 2021

47. Spatio-temporal dynamics of turbulence trapped in geodesic acoustic modes

Author: Sasaki, Makoto, Kobayashi, Tatsuya, ITOH, Kimitaka, KASUYA, Naohiro, Kosuga, Yusuke, Fujisawa, A., ITOH, Sanae -I., Sasaki, Makoto, Kobayashi, Tatsuya, ITOH, Kimitaka, KASUYA, Naohiro, Kosuga, Yusuke, Fujisawa, A., and ITOH, Sanae -I.
Abstract: The spatio-temporal dynamics of turbulence with the interaction of geodesic acoustic modes (GAMs) are investigated, focusing on the phase-space structure of turbulence, where the phase-space consists of real-space and wavenumber-space. Based on the wave-kinetic framework, the coupling equation between the GAM and the turbulence is numerically solved. The turbulence trapped by the GAM velocity field is obtained. Due to the trapping effect, the turbulence intensity increases where the second derivative of the GAM velocity (curvature of the GAM) is negative. While, in the positive-curvature region, the turbulence is suppressed. Since the trapped turbulence propagates with the GAMs, this relationship is sustained spatially and temporally. The dynamics of the turbulence in the wavenumber spectrum are converted in the evolution of the frequency spectrum, and the simulation result is compared with the experimental observation in JFT-2M tokamak, where the similar patterns are obtained. The turbulence trapping effect is a key to understand the spatial structure of the turbulence in the presence of sheared flows., source:Physics of Plasmas 25, 012316 (2018); https://doi.org/10.1063/1.5008541, source:https://doi.org/10.1063/1.5008541
Published: 2021

48. Neutral particle drag on parallel flow shear driven instability

Author: Sasaki, Makoto, Kobayashi, Tatsuya, INAGAKI, Shigeru, KASUYA, Naohiro, Kosuga, Yusuke, Sasaki, Makoto, Kobayashi, Tatsuya, INAGAKI, Shigeru, KASUYA, Naohiro, and Kosuga, Yusuke
Abstract: The neutral drag effect on the parallel velocity gradient driven instability (PVG) in the presence of density inhomogeneity is theoretically investigated. The dispersion relation of PVG mode with the effect of the density gradient and neutral particle drag is derived, and its solution is analytically obtained. The neutral particle drag gives rise to the phase shift between parallel flow and electrostatic potential fluctuations and modifies the parallel compression. As a result, the stability of the PVG mode changes. It is found that the neutral particle drag does not only reduce but also enhances the instability. Specifically, near the marginal condition, the neutral particle effect suppresses the density gradient effect, and the parameter region where the PVG mode is linearly unstable significantly expands., source:Physics of Plasmas 27, 082105 (2020); https://doi.org/10.1063/5.0011025, source:https://doi.org/10.1063/5.0011025, identifier:0000-0001-6835-1569
Published: 2021

49. Evaluation of abrupt energy transfer among turbulent plasma structures using singular value decomposition

Author: Sasaki, Makoto, Kobayashi, Tatsuya, DENDY, R.O., Kawachi, Y., Arakawa, H., INAGAKI, Shigeru, Sasaki, Makoto, Kobayashi, Tatsuya, DENDY, R.O., Kawachi, Y., Arakawa, H., and INAGAKI, Shigeru
Abstract: A method to quantify the energy transfer among turbulent structures using singular value decomposition (SVD) is presented. We apply the method to numerical turbulence data obtained from a global plasma simulation using the Hasegawa–Wakatani fluid model, in which the Kelvin–Helmholtz instability plays a dominant role. Using the SVD method, the electrostatic potential is decomposed into a background potential deformation, a zonal flow, a coherent mode and an intermittent structure. Thus there are four key structures, as distinct from the three found in conventional theory. The kinetic energy of each structure is evaluated, and the limit cycle among them is obtained. In the limit cycle, an abrupt change of the background is found to be synchronised with the period of the zonal flow. The energy transfer function of each turbulence structure, which is defined on the basis of a vorticity equation, is evaluated. This then provides physical understanding of how the limit cycle is sustained by dynamical changes in the energy transfer among structures over the its period. In addition, it is shown that the abrupt deformation of the background is caused by the non-linear self-coupling of the intermittent structure., source:Citation M Sasaki et al 2021 Plasma Phys. Control. Fusion 63 025004, source:https://doi.org/10.1088/1361-6587/abcb46, identifier:0000-0001-6835-1569
Published: 2021

50. Guidelines for Management of Idiopathic Normal Pressure Hydrocephalus (Third Edition): Endorsed by the Japanese Society of Normal Pressure Hydrocephalus.

Author: Nakajima, Madoka, Yamada, Shigeki, Miyajima, Masakazu, Ishii, Kazunari, Kuriyama, Nagato, Kazui, Hiroaki, Kanemoto, Hideki, Suehiro, Takashi, Yoshiyama, Kenji, Kameda, Masahiro, Kajimoto, Yoshinaga, Mase, Mitsuhito, Murai, Hisayuki, Kita, Daisuke, Kimura, Teruo, Samejima, Naoyuki, Tokuda, Takahiko, Kaijima, Mitsunobu, Akiba, Chihiro, Kawamura, Kaito, Atsuchi, Masamichi, Hirata, Yoshihumi, Matsumae, Mitsunori, Sasaki, Makoto, Yamashita, Fumio, Aoki, Shigeki, Irie, Ryusuke, Miyake, Hiroji, Kato, Takeo, Mori, Etsuro, Ishikawa, Masatsune, Date, Isao, Arai, Hajime, Takahiko, Tokuda, Nakajima, Madoka, Yamada, Shigeki, Miyajima, Masakazu, Ishii, Kazunari, Kuriyama, Nagato, Kazui, Hiroaki, Kanemoto, Hideki, Suehiro, Takashi, Yoshiyama, Kenji, Kameda, Masahiro, Kajimoto, Yoshinaga, Mase, Mitsuhito, Murai, Hisayuki, Kita, Daisuke, Kimura, Teruo, Samejima, Naoyuki, Tokuda, Takahiko, Kaijima, Mitsunobu, Akiba, Chihiro, Kawamura, Kaito, Atsuchi, Masamichi, Hirata, Yoshihumi, Matsumae, Mitsunori, Sasaki, Makoto, Yamashita, Fumio, Aoki, Shigeki, Irie, Ryusuke, Miyake, Hiroji, Kato, Takeo, Mori, Etsuro, Ishikawa, Masatsune, Date, Isao, Arai, Hajime, and Takahiko, Tokuda
Abstract: Among the various disorders that manifest with gait disturbance, cognitive impairment, and urinary incontinence in the elderly population, idiopathic normal pressure hydrocephalus (iNPH) is becoming of great importance. The first edition of these guidelines for management of iNPH was published in 2004, and the second edition in 2012, to provide a series of timely, evidence-based recommendations related to iNPH. Since the last edition, clinical awareness of iNPH has risen dramatically, and clinical and basic research efforts on iNPH have increased significantly. This third edition of the guidelines was made to share these ideas with the international community and to promote international research on iNPH. The revision of the guidelines was undertaken by a multidisciplinary expert working group of the Japanese Society of Normal Pressure Hydrocephalus in conjunction with the Japanese Ministry of Health, Labour and Welfare research project. This revision proposes a new classification for NPH. The category of iNPH is clearly distinguished from NPH with congenital/developmental and acquired etiologies. Additionally, the essential role of disproportionately enlarged subarachnoid-space hydrocephalus (DESH) in the imaging diagnosis and decision for further management of iNPH is discussed in this edition. We created an algorithm for diagnosis and decision for shunt management. Diagnosis by biomarkers that distinguish prognosis has been also initiated. Therefore, diagnosis and treatment of iNPH have entered a new phase. We hope that this third edition of the guidelines will help patients, their families, and healthcare professionals involved in treating iNPH.
Published: 2021

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