The effect of transdermal glyceryl trinitrate in acute stroke patients with carotid stenosis: data from the Efficacy of Nitric Oxide in Stroke trial

Background: There is concern that blood pressure lowering in acute stroke may compromise cerebral perfusion and worsen outcome in the context of carotid stenosis. The effect of glyceryl trinitrate (GTN) on outcome in acute stroke patients with carotid stenosis is unclear. We sought to assess GTN’s effect in this context using data from the Efficacy of Nitric Oxide in Stroke (ENOS) trial. Methods: ENOS randomised 4011 patients with acute stroke and raised systolic blood pressure to transdermal GTN or no GTN within 48 hours of onset. The primary outcome was the modified Rankin Scale (mRS) at day 90. Ipsilateral carotid stenosis was split: 70%. Bilateral carotid stenosis was split: 50%. Data are odds ratios (OR) with 95% confidence intervals (CI) adjusted for baseline prognostic factors. Results: 2023 (60.5%) ischaemic stroke participants had carotid imaging. Compared with participants with 70% ipsilateral stenosis was associated with an unfavourable shift in mRS at 90 days (OR 1.88, 95% CI 1.44-2.44, p70% stenosis who received GTN had a favourable shift in mRS (OR 0.56, 95% CI 0.34-0.93, p=0.024) compared to those who received no GTN. Tendencies towards less dependency, albeit non-significant, were seen in 30-50% and 50-70% groups. No differences in mRS were seen across groups of bilateral stenosis or between those who received GTN or not. Conclusions:Severe ipsilateral carotid stenosis is associated with poorer functional outcome at 90 days following ischaemic stroke. GTN appears safe in acute stroke patients with ipsilateral or bilateral carotid stenosis

The effect of transdermal glyceryl trinitrate in acute stroke patients with carotid stenosis: data from the Efficacy of Nitric Oxide in Stroke trial

Background: There is concern that blood pressure lowering in acute stroke may compromise cerebral perfusion and worsen outcome in the context of carotid stenosis. The effect of glyceryl trinitrate (GTN) on outcome in acute stroke patients with carotid stenosis is unclear. We sought to assess GTN’s effect in this context using data from the Efficacy of Nitric Oxide in Stroke (ENOS) trial. Methods: ENOS randomised 4011 patients with acute stroke and raised systolic blood pressure to transdermal GTN or no GTN within 48 hours of onset. The primary outcome was the modified Rankin Scale (mRS) at day 90. Ipsilateral carotid stenosis was split: 70%. Bilateral carotid stenosis was split: 50%. Data are odds ratios (OR) with 95% confidence intervals (CI) adjusted for baseline prognostic factors. Results: 2023 (60.5%) ischaemic stroke participants had carotid imaging. Compared with participants with 70% ipsilateral stenosis was associated with an unfavourable shift in mRS at 90 days (OR 1.88, 95% CI 1.44-2.44, p70% stenosis who received GTN had a favourable shift in mRS (OR 0.56, 95% CI 0.34-0.93, p=0.024) compared to those who received no GTN. Tendencies towards less dependency, albeit non-significant, were seen in 30-50% and 50-70% groups. No differences in mRS were seen across groups of bilateral stenosis or between those who received GTN or not. Conclusions:Severe ipsilateral carotid stenosis is associated with poorer functional outcome at 90 days following ischaemic stroke. GTN appears safe in acute stroke patients with ipsilateral or bilateral carotid stenosis

Robo-AO M-dwarf Multiplicity Survey: Catalog

We analyze observations from Robo-AO's field M dwarf survey taken on the 2.1 m Kitt Peak telescope and perform a multiplicity comparison with Gaia DR2. Through its laser-guided, automated system, the Robo-AO instrument has yielded the largest adaptive optics M dwarf multiplicity survey to date. After developing an interface to visually identify and locate stellar companions, we selected 11 low-significance Robo-AO detections for follow-up on the Keck II telescope using NIRC2. In the Robo-AO survey we find 553 candidate companions within 4″ around 534 stars out of 5566 unique targets, most of which are new discoveries. Using a position cross-match with DR2 on all targets, we assess the binary recoverability of Gaia DR2 and compare the properties of multiples resolved by both Robo-AO and Gaia. The catalog of nearby M dwarf systems and their basic properties presented here can assist other surveys which observe these stars, such as the NASA TESS mission

Primary stroke prevention worldwide : translating evidence into action

Funding Information: The stroke services survey reported in this publication was partly supported by World Stroke Organization and Auckland University of Technology. VLF was partly supported by the grants received from the Health Research Council of New Zealand. MOO was supported by the US National Institutes of Health (SIREN U54 HG007479) under the H3Africa initiative and SIBS Genomics (R01NS107900, R01NS107900-02S1, R01NS115944-01, 3U24HG009780-03S5, and 1R01NS114045-01), Sub-Saharan Africa Conference on Stroke Conference (1R13NS115395-01A1), and Training Africans to Lead and Execute Neurological Trials & Studies (D43TW012030). AGT was supported by the Australian National Health and Medical Research Council. SLG was supported by a National Heart Foundation of Australia Future Leader Fellowship and an Australian National Health and Medical Research Council synergy grant. We thank Anita Arsovska (University Clinic of Neurology, Skopje, North Macedonia), Manoj Bohara (HAMS Hospital, Kathmandu, Nepal), Denis ?erimagi? (Poliklinika Glavi?, Dubrovnik, Croatia), Manuel Correia (Hospital de Santo Ant?nio, Porto, Portugal), Daissy Liliana Mora Cuervo (Hospital Moinhos de Vento, Porto Alegre, Brazil), Anna Cz?onkowska (Institute of Psychiatry and Neurology, Warsaw, Poland), Gloria Ekeng (Stroke Care International, Dartford, UK), Jo?o Sargento-Freitas (Centro Hospitalar e Universit?rio de Coimbra, Coimbra, Portugal), Yuriy Flomin (MC Universal Clinic Oberig, Kyiv, Ukraine), Mehari Gebreyohanns (UT Southwestern Medical Centre, Dallas, TX, USA), Ivete Pillo Gon?alves (Hospital S?o Jos? do Avai, Itaperuna, Brazil), Claiborne Johnston (Dell Medical School, University of Texas, Austin, TX, USA), Kristaps Jurj?ns (P Stradins Clinical University Hospital, Riga, Latvia), Rizwan Kalani (University of Washington, Seattle, WA, USA), Grzegorz Kozera (Medical University of Gda?sk, Gda?sk, Poland), Kursad Kutluk (Dokuz Eylul University, ?zmir, Turkey), Branko Malojcic (University Hospital Centre Zagreb, Zagreb, Croatia), Micha? Maluchnik (Ministry of Health, Warsaw, Poland), Evija Migl?ne (P Stradins Clinical University Hospital, Riga, Latvia), Cassandra Ocampo (University of Botswana, Princess Marina Hospital, Botswana), Louise Shaw (Royal United Hospitals Bath NHS Foundation Trust, Bath, UK), Lekhjung Thapa (Upendra Devkota Memorial-National Institute of Neurological and Allied Sciences, Kathmandu, Nepal), Bogdan Wojtyniak (National Institute of Public Health, Warsaw, Poland), Jie Yang (First Affiliated Hospital of Chengdu Medical College, Chengdu, China), and Tomasz Zdrojewski (Medical University of Gda?sk, Gda?sk, Poland) for their comments on early draft of the manuscript. The views expressed in this article are solely the responsibility of the authors and they do not necessarily reflect the views, decisions, or policies of the institution with which they are affiliated. We thank WSO for funding. The funder had no role in the design, data collection, analysis and interpretation of the study results, writing of the report, or the decision to submit the study results for publication. Funding Information: The stroke services survey reported in this publication was partly supported by World Stroke Organization and Auckland University of Technology. VLF was partly supported by the grants received from the Health Research Council of New Zealand. MOO was supported by the US National Institutes of Health (SIREN U54 HG007479) under the H3Africa initiative and SIBS Genomics (R01NS107900, R01NS107900-02S1, R01NS115944-01, 3U24HG009780-03S5, and 1R01NS114045-01), Sub-Saharan Africa Conference on Stroke Conference (1R13NS115395-01A1), and Training Africans to Lead and Execute Neurological Trials & Studies (D43TW012030). AGT was supported by the Australian National Health and Medical Research Council. SLG was supported by a National Heart Foundation of Australia Future Leader Fellowship and an Australian National Health and Medical Research Council synergy grant. We thank Anita Arsovska (University Clinic of Neurology, Skopje, North Macedonia), Manoj Bohara (HAMS Hospital, Kathmandu, Nepal), Denis Čerimagić (Poliklinika Glavić, Dubrovnik, Croatia), Manuel Correia (Hospital de Santo António, Porto, Portugal), Daissy Liliana Mora Cuervo (Hospital Moinhos de Vento, Porto Alegre, Brazil), Anna Członkowska (Institute of Psychiatry and Neurology, Warsaw, Poland), Gloria Ekeng (Stroke Care International, Dartford, UK), João Sargento-Freitas (Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal), Yuriy Flomin (MC Universal Clinic Oberig, Kyiv, Ukraine), Mehari Gebreyohanns (UT Southwestern Medical Centre, Dallas, TX, USA), Ivete Pillo Gonçalves (Hospital São José do Avai, Itaperuna, Brazil), Claiborne Johnston (Dell Medical School, University of Texas, Austin, TX, USA), Kristaps Jurjāns (P Stradins Clinical University Hospital, Riga, Latvia), Rizwan Kalani (University of Washington, Seattle, WA, USA), Grzegorz Kozera (Medical University of Gdańsk, Gdańsk, Poland), Kursad Kutluk (Dokuz Eylul University, İzmir, Turkey), Branko Malojcic (University Hospital Centre Zagreb, Zagreb, Croatia), Michał Maluchnik (Ministry of Health, Warsaw, Poland), Evija Miglāne (P Stradins Clinical University Hospital, Riga, Latvia), Cassandra Ocampo (University of Botswana, Princess Marina Hospital, Botswana), Louise Shaw (Royal United Hospitals Bath NHS Foundation Trust, Bath, UK), Lekhjung Thapa (Upendra Devkota Memorial-National Institute of Neurological and Allied Sciences, Kathmandu, Nepal), Bogdan Wojtyniak (National Institute of Public Health, Warsaw, Poland), Jie Yang (First Affiliated Hospital of Chengdu Medical College, Chengdu, China), and Tomasz Zdrojewski (Medical University of Gdańsk, Gdańsk, Poland) for their comments on early draft of the manuscript. The views expressed in this article are solely the responsibility of the authors and they do not necessarily reflect the views, decisions, or policies of the institution with which they are affiliated. We thank WSO for funding. The funder had no role in the design, data collection, analysis and interpretation of the study results, writing of the report, or the decision to submit the study results for publication. Funding Information: VLF declares that the PreventS web app and Stroke Riskometer app are owned and copyrighted by Auckland University of Technology; has received grants from the Brain Research New Zealand Centre of Research Excellence (16/STH/36), Australian National Health and Medical Research Council (NHMRC; APP1182071), and World Stroke Organization (WSO); is an executive committee member of WSO, honorary medical director of Stroke Central New Zealand, and CEO of New Zealand Stroke Education charitable Trust. AGT declares funding from NHMRC (GNT1042600, GNT1122455, GNT1171966, GNT1143155, and GNT1182017), Stroke Foundation Australia (SG1807), and Heart Foundation Australia (VG102282); and board membership of the Stroke Foundation (Australia). SLG is funded by the National Health Foundation of Australia (Future Leader Fellowship 102061) and NHMRC (GNT1182071, GNT1143155, and GNT1128373). RM is supported by the Implementation Research Network in Stroke Care Quality of the European Cooperation in Science and Technology (project CA18118) and by the IRIS-TEPUS project from the inter-excellence inter-cost programme of the Ministry of Education, Youth and Sports of the Czech Republic (project LTC20051). BN declares receiving fees for data management committee work for SOCRATES and THALES trials for AstraZeneca and fees for data management committee work for NAVIGATE-ESUS trial from Bayer. All other authors declare no competing interests. Publisher Copyright: © 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 licenseStroke is the second leading cause of death and the third leading cause of disability worldwide and its burden is increasing rapidly in low-income and middle-income countries, many of which are unable to face the challenges it imposes. In this Health Policy paper on primary stroke prevention, we provide an overview of the current situation regarding primary prevention services, estimate the cost of stroke and stroke prevention, and identify deficiencies in existing guidelines and gaps in primary prevention. We also offer a set of pragmatic solutions for implementation of primary stroke prevention, with an emphasis on the role of governments and population-wide strategies, including task-shifting and sharing and health system re-engineering. Implementation of primary stroke prevention involves patients, health professionals, funders, policy makers, implementation partners, and the entire population along the life course.publishersversionPeer reviewe

TOI 122b and TOI 237b: Two Small Warm Planets Orbiting Inactive M Dwarfs Found by TESS

We report the discovery and validation of TOI 122b and TOI 237b, two warm planets transiting inactive M dwarfs observed by the Transiting Exoplanet Survey Satellite (TESS). Our analysis shows that TOI 122b has a radius of 2.72 ± 0.18 R ⊕ and receives 8.8 ± 1.0 times Earth's bolometric insolation, and TOI 237b has a radius of 1.44±0.12 R ⊕ and receives 3.7 ± 0.5 times Earth's insolation, straddling the 6.7 Earth insolation that Mercury receives from the Sun. This makes these two of the cooler planets yet discovered by TESS, even on their 5.08 and 5.43 day orbits. Together, they span the small-planet radius valley, providing useful laboratories for exploring volatile evolution around M dwarfs. Their relatively nearby distances (62.23 ± 0.21 pc and 38.11 ± 0.23 pc, respectively) make them potentially feasible targets for future radial velocity follow-up and atmospheric characterization, although such observations may require substantial investments of time on large telescopes

TESS discovery of a super-earth and three sub-neptunes hosted by the bright, sunlike star HD 108236

We report the discovery and validation of four extrasolar planets hosted by the nearby, bright, Sun-like (G3V) star HD 108236 using data from the Transiting Exoplanet Survey Satellite (TESS). We present transit photometry, reconnaissance, and precise Doppler spectroscopy, as well as high-resolution imaging, to validate the planetary nature of the objects transiting HD 108236, also known as the TESS Object of Interest (TOI) 1233. The innermost planet is a possibly rocky super-Earth with a period of 3.79523+0.00047-0.00044 days and has a radius of 1.586 ± 0.098 R⊗.The outer planets are sub-Neptunes, with potential gaseous envelopes, having radii of 2.068+0.10-0.091 R⊗, 2.72 ± 0.11 R⊗, and 3.12+0.13-0.12 R⊗ and periods of 6.20370+0.00064-0.00052 days, 14.17555+0.00099-0.0011 days, and 19.5917+0.0022-0.0020 days, respectively. With V and Ks magnitudes of 9.2 and 7.6, respectively, the bright host star makes the transiting planets favorable targets for mass measurements and, potentially, for atmospheric characterization via transmission spectroscopy. HD 108236 is the brightest Sun-like star in the visual (V ) band known to host four or more transiting exoplanets. The discovered planets span a broad range of planetary radii and equilibrium temperatures and share a common history of insolation from a Sun-like star (R∗ = 0.888 ± 0.017 R⊙, Teff = 5730 ± 50 K), making HD 108236 an exciting, opportune cosmic laboratory for testing models of planet formation and evolution

TOI-1231 b: A Temperate, Neptune-sized Planet Transiting the Nearby M3 Dwarf NLTT 24399

We report the discovery of a transiting, temperate, Neptune-sized exoplanet orbiting the nearby (d = 27.5 pc), M3V star TOI-1231 (NLTT 24399, L 248-27, 2MASS J10265947-5228099). The planet was detected using photometric data from the Transiting Exoplanet Survey Satellite and followed up with observations from the Las Cumbres Observatory and the Antarctica Search for Transiting ExoPlanets program. Combining the photometric data sets, we find that the newly discovered planet has a radius of {3.65}_{-0.15}^{+0.16}\,{R}_{\oplus } and an orbital period of 24.246 days. Radial velocity measurements obtained with the Planet Finder Spectrograph on the Magellan Clay telescope confirm the existence of the planet and lead to a mass measurement of 15.5 3.3 M ⊕. With an equilibrium temperature of just 330 K, TOI-1231 b is one of the coolest small planets accessible for atmospheric studies thus far, and its host star's bright near-infrared brightness (J = 8.88, Ks = 8.07) makes it an exciting target for the Hubble Space Telescope and the James Webb Space Telescope. Future atmospheric observations would enable the first comparative planetology efforts in the 250-350 K temperature regime via comparisons with K2-18 b. Furthermore, TOI-1231's high systemic radial velocity (70.5 km s-1) may allow for the detection of low-velocity hydrogen atoms escaping the planet by Doppler, shifting the H i Lyα stellar emission away from the geocoronal and interstellar medium absorption features

Combining Asian and European genome-wide association studies of colorectal cancer improves risk prediction across racial and ethnic populations

Polygenic risk scores (PRS) have great potential to guide precision colorectal cancer (CRC) prevention by identifying those at higher risk to undertake targeted screening. However, current PRS using European ancestry data have sub-optimal performance in non-European ancestry populations, limiting their utility among these populations. Towards addressing this deficiency, we expand PRS development for CRC by incorporating Asian ancestry data (21,731 cases; 47,444 controls) into European ancestry training datasets (78,473 cases; 107,143 controls). The AUC estimates (95% CI) of PRS are 0.63(0.62-0.64), 0.59(0.57-0.61), 0.62(0.60-0.63), and 0.65(0.63-0.66) in independent datasets including 1681-3651 cases and 8696-115,105 controls of Asian, Black/African American, Latinx/Hispanic, and non-Hispanic White, respectively. They are significantly better than the European-centric PRS in all four major US racial and ethnic groups (p-values < 0.05). Further inclusion of non-European ancestry populations, especially Black/African American and Latinx/Hispanic, is needed to improve the risk prediction and enhance equity in applying PRS in clinical practice