Genome-wide meta-analysis of cerebral white matter hyperintensities in patients with stroke.

OBJECTIVE: For 3,670 stroke patients from the United Kingdom, United States, Australia, Belgium, and Italy, we performed a genome-wide meta-analysis of white matter hyperintensity volumes (WMHV) on data imputed to the 1000 Genomes reference dataset to provide insights into disease mechanisms. METHODS: We first sought to identify genetic associations with white matter hyperintensities in a stroke population, and then examined whether genetic loci previously linked to WMHV in community populations are also associated in stroke patients. Having established that genetic associations are shared between the 2 populations, we performed a meta-analysis testing which associations with WMHV in stroke-free populations are associated overall when combined with stroke populations. RESULTS: There were no associations at genome-wide significance with WMHV in stroke patients. All previously reported genome-wide significant associations with WMHV in community populations shared direction of effect in stroke patients. In a meta-analysis of the genome-wide significant and suggestive loci (p < 5 × 10(-6)) from community populations (15 single nucleotide polymorphisms in total) and from stroke patients, 6 independent loci were associated with WMHV in both populations. Four of these are novel associations at the genome-wide level (rs72934505 [NBEAL1], p = 2.2 × 10(-8); rs941898 [EVL], p = 4.0 × 10(-8); rs962888 [C1QL1], p = 1.1 × 10(-8); rs9515201 [COL4A2], p = 6.9 × 10(-9)). CONCLUSIONS: Genetic associations with WMHV are shared in otherwise healthy individuals and patients with stroke, indicating common genetic susceptibility in cerebral small vessel disease.Funding for collection, genotyping, and analysis of stroke samples was provided by Wellcome Trust Case Control Consortium-2, a functional genomics grant from the Wellcome Trust (DNA-Lacunar), the Stroke Association (DNA-lacunar), the Intramural Research Program of National Institute of Ageing (Massachusetts General Hospital [MGH] and Ischemic Stroke Genetics Study [ISGS]), National Institute of Neurological Disorders and Stroke (Siblings With Ischemic Stroke Study, ISGS, and MGH), the American Heart Association/Bugher Foundation Centers for Stroke Prevention Research (MGH), Deane Institute for Integrative Study of Atrial Fibrillation and Stroke (MGH), National Health and Medical Research Council (Australian Stroke Genetics Collaborative), and Italian Ministry of Health (Milan). Additional support for sample collection came from the Medical Research Council, National Institute of Health Research Biomedical Research Centre and Acute Vascular Imaging Centre (Oxford), Wellcome Trust and Binks Trust (Edinburgh), and Vascular Dementia Research Foundation (Munich). MT is supported by a project grant from the Stroke Association (TSA 2013/01). HSM is supported by an NIHR Senior Investigator award. HSM and SB are supported by the NIHR Cambridge University Hospitals Comprehensive Biomedical Research Centre. VT and RL are supported by grants from FWO Flanders. PR holds NIHR and Wellcome Trust Senior Investigator Awards. PAS is supported by an MRC Fellowship. CML’s research is supported by the National Institute for Health Research Biomedical Research Centre (BRC) based at Guy's and St Thomas' NHS Foundation Trust and King's College London, and the BRC for Mental Health at South London and Maudsley NHS Foundation Trust and King’s College London. This is the final version of the article. It first appeared from Wolters Kluwer via http://dx.doi.org/10.1212/WNL.000000000000226

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

Atrial fibrillation genetic risk differentiates cardioembolic stroke from other stroke subtypes

AbstractObjectiveWe sought to assess whether genetic risk factors for atrial fibrillation can explain cardioembolic stroke risk.MethodsWe evaluated genetic correlations between a prior genetic study of AF and AF in the presence of cardioembolic stroke using genome-wide genotypes from the Stroke Genetics Network (N = 3,190 AF cases, 3,000 cardioembolic stroke cases, and 28,026 referents). We tested whether a previously-validated AF polygenic risk score (PRS) associated with cardioembolic and other stroke subtypes after accounting for AF clinical risk factors.ResultsWe observed strong correlation between previously reported genetic risk for AF, AF in the presence of stroke, and cardioembolic stroke (Pearson’s r=0.77 and 0.76, respectively, across SNPs with p &lt; 4.4 × 10−4 in the prior AF meta-analysis). An AF PRS, adjusted for clinical AF risk factors, was associated with cardioembolic stroke (odds ratio (OR) per standard deviation (sd) = 1.40, p = 1.45×10−48), explaining ∼20% of the heritable component of cardioembolic stroke risk. The AF PRS was also associated with stroke of undetermined cause (OR per sd = 1.07, p = 0.004), but no other primary stroke subtypes (all p &gt; 0.1).ConclusionsGenetic risk for AF is associated with cardioembolic stroke, independent of clinical risk factors. Studies are warranted to determine whether AF genetic risk can serve as a biomarker for strokes caused by AF.</jats:sec

Stress analysis in ceramic rolling elements

Materiały ceramiczne od kilkunastu lat znajdują coraz większe zastosowanie w technice. Wynika to z charakterystycznych właściwości materiałów ceramicznych takich, jak duża twardość, odporność na korozję, możliwość stosowania w środowiskach agresywnie chemicznych, a także z uwagi na mniejszy ciężar właściwy w porównaniu z materiałami stalowymi. Przykładem zastosowań tej grupy materiałowej mogą być: powłoki ceramiczne nakładane na powierzchnie cylindrów silników samochodowych, elementy pomp drukarskich, elementy zaworów kulowych itp. Materiały ceramiczne znajdują także zastosowanie w inżynierii łożyskowania, czego dowodem są między innymi hybrydowe łożyska toczne. Jednak zastosowanie materiałów ceramicznych wiąże się z wieloma ograniczeniami. Podstawową ich wadą jest mała odporność na kruche pękanie, która wiąże się z ich strukturą chemiczną i właściwościami mechanicznymi. Drogą do szerokiego zastosowania tego typu materiałów jest znajomość mechanizmów propagacji pęknięć i momentu ich inicjacji w określonych warunkach pracy. W pracy przeprowadzono metodą elementów skończonych (MES) analizę stanu naprężenia w strefie pęknięcia kolistego kulki ceramicznej wykonanej z azotku krzemu poddanej naciskom hertzowskim. Naprężenia analizowano dla pęknięć, które najczęściej są spotykane na powierzchni kulek ceramicznych. Obliczenia numeryczne prowadzono za pomocą programu ANSYS. Rozwiązania numeryczne porównywano z wynikami badań doświadczalnych propagacji tego typu pęknięć.Some ceramic materials have been found to have the optimum combination of properties that are suitable for rolling element bearing applications (high speeds, high loads, different environments). Cracks, structure defects, and manufacturing faults are the main problem connected with fatigue life. These defects decrease the rolling contact fatigue considerably. A stress analysis of crack propagation by the finite element method of silicon nitride material was described in the paper. Ring cracks were modelled based on microscopic analysis of artificial induced cracks made onto silicon nitride balls. The stress analysis of cracks was performed in relation to the contact position of two ceramic balls. Numerical stress analysis shows that the maximum value of von Mises stresses is 0.04 – 0.05 mm below the ceramic ball surface where the cracks change direction. The results are in accordance with experimental research and confirm that crack propagation takes place directly below the ball surface

Fatigue life limitation of ceramic materials due to surface crack propagation

Materiały ceramiczne od kilkunastu lat znajdują coraz większe zastosowanie w technice. Wynika to z charakterystycznych właściwości materiałów ceramicznych, takich jak: duża twardość, odporność na korozję, możliwość stosowania w środowiskach agresywnie chemicznych, a także z uwagi na mniejszy ciężar właściwy w porównaniu z materiałami stalowymi. Przykładem zastosowań tej grupy materiałowej mogą być: powłoki ceramiczne nakładane na powierzchnie cylindrów silników samochodowych, elementy pomp drukarskich, elementy zaworów kulowych itp. Materiały ceramiczne znajdują także zastosowanie w inżynierii łożyskowania, czego dowodem są między innymi hybrydowe łożyska toczne. Jednak zastosowanie materiałów ceramicznych wiąże się z wieloma ograniczeniami. Podstawową ich wadą jest mała odporność na kruche pękanie, która wiąże się z ich strukturą chemiczną i właściwościami mechanicznymi. Drogą do szerokiego zastosowania tego typu materiałów jest znajomość mechanizmów propagacji pęknięć i momentu ich inicjacji w określonych warunkach pracy. W niniejszym artykule przedstawiona została krótka analiza literaturowa dotycząca mechanizmów propagacji pęknięć w materiałach ceramicznych oraz wyniki dotychczasowych badań doświadczalnych wybranych materiałów ceramicznych z uwzględnieniem wpływu pęknięć powierzchniowych na trwałość ceramicznych skojarzeń tocznych.Some ceramic materials have been found to have the optimum combination of properties that are suitable for rolling element bearing applications (high speeds, high loads, different environments). Cracks, structure defects and manufacturing faults are the main problem connected with fatigue life. These defects decrease the rolling contact fatigue considerably. An experimental study of ring cracks propagation and structure defects propagation of zirconia and silicon nitride was also described in the paper. The rolling contact tests were performed on pre-cracked zirconia and silicon nitride upper balls using a modified (rolling lower balls) four-ball machine in specified lubricant. Ball surfaces and failures were examined using scanning electron microscopy. The paper contains the following: - The variation of test time for both ceramic materials balls with ring cracks defects was presented. - The mechanism of ring crack propagation in zirconia and silicon nitride was described. - The influence of pores on fatigue life of zirconia was described

Surface cracks of ceramic rolling elements

Materiały ceramiczne posiadają kombinację optymalnych własności, które są niezbędne w zastosowaniach na wysoko obciążone elementy maszyn. Podstawowym problemem związanym z wytrzymałością zmęczeniową materiałów ceramicznych są wszelkiego rodzaju wady powierzchniowe będące efektem procesu wytwarzania lub wynikające z defektów struktury materiału ceramicznego. W artykule przedstawiono badania doświadczalne dwutlenku cyrkonu ze sztucznie wprowadzonymi, kontrolowanymi pęknięciami kolistym. Badania dwutlenku cyrkonu w postaci kulek prowadzono w układzie czterokulowym przy smarowaniu olejem.Zirconia is one of the most important ceramic materials for bearing applications (high speeds, different environments). The main problems connected with fatigue life are ring crack defects as the effect of manufacture or defects due to material structure. These defects decrease the rolling contact fatigue considerably. An experimental study of ring cracks propagation of zirconia ZrO2(MgO) was described in the paper. The rolling contact tests were performed on pre-cracks zirconia upper ball using a modified (rolling lower balls) four-ball machine in specified lubricant. Ball surfaces and failures were examined using scanning electron microscopy

Gęstość umowna drewna świerka pospolitego (Picea abies [L.] Karst.) pochodzącego z powierzchni doświadczalnej zlokalizowanej na terenie Leśnego Zakładu Doświadczalnego Siemianice

The paper presents a comparison of the density of seven provenances of spruce trees, grown on an experimental plot located at Siemianice Forest Experimental Station. This plot is a unique research area on which observations concerning the growth of spruce trees of different provenances have been conducted for 41 years. The conditions in which the trees grow are very similar and it may be assumed that provenance is the element differentiating growth and wood properties. Trees growing on this plot have reached such large dimensions that it was possible to collect experimental material in the form of blocks, from which wood samples for further tests were obtained. Analyses were conducted on 651 samples collected from spruce trees of 7 provenances (Orawa, Międzygórze, Nowe Ramuki, Istebna Bukowiec, Kartuzy, Zwierzyniec 281B, Zwierzyniec Lubelski). The results indicated that wood of each individual provenance differed significantly in terms of the analysed trait. It was found that wood coming from Zwierzyniec Lubelski had the greatest values of basic density, while the lowest values were recorded for the Orawa provenance. Moreover, the examined provenances were divided into four groups, thus creating a ranking list of provenances in terms of the basic wood density of Norway spruce.Artykuł zawiera porównanie gęstości siedmiu proweniencji świerka wyrosłych na powierzchni doświadczalnej na terenie LZD Siemianice. Powierzchnia ta jest unikatowym obiektem badawczym, na którym od wielu lat prowadzone są obserwacje dotyczące wzrostu świerka różnych pochodzeń. Warunki, w których wzrastają drzewa są do siebie bardzo zbliżone i można przyjąć, że elementem różnicującym wzrost i właściwości drewna jest ich pochodzenie. Drzewa rosnące na powierzchni osiągnęły na tyle duże rozmiary, że możliwym było pozyskanie materiału badawczego w formie wyrzynków, z których wyrobiono próbki drewna do dalszych badań. Badania przeprowadzono na 651 próbkach pozyskanych z 7 pochodzeń (Orawa, Międzygórze, Nowe Ramuki, Istebna Bukowiec, Kartuzy, Zwierzyniec, Zwierzyniec Lubelski). Uzyskane wyniki pozwalają stwierdzić,że drewno z poszczególnych pochodzeń istotnie różni się w zakresie badanej cechy. Ustalono, że w zakresie gęstości umownej najwyższe wartości przyjmuje drewno pochodzenia Zwierzyniec Lubelski, a najmniejsze wartości z proweniencji Orawa. Dokonano również podziału badanych pochodzeń na cztery grupy, tworząc tym samym „listę rankingową” najlepszych pochodzeń świerka pospolitego