Search

Your search keyword '"Maguire, J."' showing total 1,916 results
Start Over Author "Maguire, J."
1,916 results on '"Maguire, J."'

2. Topological polarization networking in uniaxial ferroelectrics

Author

Tikhonov, Y., Maguire, J. R., McCluskey, C. J., McConville, J. P. V., Kumar, A., Meier, D., Razumnaya, A., Gregg, J. M., Gruverman, A., Vinokur, V. M., and Luk'yanchuk, I.

Subjects
Condensed Matter - Materials Science, Condensed Matter - Mesoscale and Nanoscale Physics
Abstract

Discovery of topological polarization textures has put ferroelectrics at the frontier of topological matter science. High-symmetry ferroelectric oxide materials allowing for freedom of the polarization vector rotation offer a fertile ground for emergent topological polar formations, like vortices, skyrmions, merons, and Hopfions. It has been commonly accepted that uniaxial ferroelectrics do not belong in the topological universe because strong anisotropy imposes insurmountable energy barriers for topological excitations. Here we show that uniaxial ferroelectrics provide unique opportunity for the formation of topological polarization networks comprising branching intertwined domains with opposite counterflowing polarization. We report that they host the topological state of matter: a crisscrossing structure of topologically protected colliding head-to-head and tail-to-tail polarization domains, which for decades has been considered impossible from the electrostatic viewpoint. The domain wall interfacing the counterflowing domains is a multiconnected surface, propagating through the whole volume of the ferroelectric.

Published
2022

6. Electrically pumped single-defect light emitters in WSe$_2$

Author

Schwarz, S., Kozikov, A., Withers, F., Maguire, J. K., Foster, A. P., Dufferwiel, S., Hague, L., Makhonin, M. N., Wilson, L. R., Geim, A . K., Novoselov, K. S., and Tartakovskii, A. I.

Subjects
Physics - Optics, Condensed Matter - Mesoscale and Nanoscale Physics
Abstract

Recent developments in fabrication of van der Waals heterostructures enable new type of devices assembled by stacking atomically thin layers of two-dimensional materials. Using this approach, we fabricate light-emitting devices based on a monolayer WSe$_2$, and also comprising boron nitride tunnelling barriers and graphene electrodes, and observe sharp luminescence spectra from individual defects in WSe$_2$ under both optical and electrical excitation. This paves the way towards the realization of electrically-pumped quantum emitters in atomically thin semiconductors. In addition we demonstrate tuning by more than 1 meV of the emission energy of the defect luminescence by applying a vertical electric field. This provides an estimate of the permanent electric dipole created by the corresponding electron-hole pair. The light-emitting devices investigated in our work can be assembled on a variety of substrates enabling a route to integration of electrically pumped single quantum emitters with existing technologies in nano-photonics and optoelectronics.

Published
2016
Full Text
View/download PDF

8. Scholarly literature on nurses and pharmacogenomics: A scoping review.

Author

Hetland, LH, Maguire, J, Debono, D, Wright, H, Hetland, LH, Maguire, J, Debono, D, and Wright, H

Abstract

BACKGROUND: Pharmacogenomics is the bioscience investigating how genes affect medication responses. Nurses are instrumental in medication safety. Pharmacogenomics is slowly being integrated into healthcare, and knowledge and understanding of it is now pertinent to nursing practice. PURPOSE: This paper aims to map the scholarly literature on pharmacogenomics in relation to nurses. METHODS: A scoping review was conducted in four databases: CINAHL, Embase (Ovid), ProQuest Health and Medicine and PubMed using the search terms pharmacogenomic*, pharmacogenetic*, PGx*, and nurs*, resulting in 263 articles of which 77 articles met the inclusion criteria. FINDINGS: Most articles (85 %, n = 65) were non-empirical and 12 presented empirical data (15 %, n = 12). The articles were USA-centric (81 %, n = 62) and represented a broad range of nursing specialties. CONCLUSION: The majority of scholarly literature on nurses and pharmacogenomics is narrative reviews. Further empirical research is warranted to investigate nurses' current knowledge levels and potential involvement with pharmacogenomics in clinical practice.

Published
2024

9. Achieving consensus on the essential knowledge and skills needed by nursing students to promote planetary health and sustainable healthcare: A Delphi study.

Author

Levett-Jones, T, Catling, C, Cheer, S, Fields, L, Foster, A, Maguire, J, Mcintyre, E, Moroney Oam, T, Pich, J, Pitt, V, Whiteing, N, Lokmic-Tomkins, Z, Levett-Jones, T, Catling, C, Cheer, S, Fields, L, Foster, A, Maguire, J, Mcintyre, E, Moroney Oam, T, Pich, J, Pitt, V, Whiteing, N, and Lokmic-Tomkins, Z

Abstract

AIM: To achieve consensus on the knowledge and skills that undergraduate/pre-licensure nursing students require to steward healthcare towards a more sustainable future. DESIGN: A two-phase real-time Delphi study. METHODS: Phase 1 included the generation of Planetary Health, climate change and sustainability knowledge and skill statements based on a review of relevant literature. Phase 2 consisted of a real-time Delphi survey designed to seek consensus on the proposed statements from a panel of 42 international experts. RESULTS: Of the 49 survey statements, 44 (90%) achieved ≥75% consensus and 26 (53%) achieved ≥80% consensus. Three were removed and 32 were modified to improve clarity of language. CONCLUSION: The knowledge and skills statements that emerged through this Delphi study can serve as a guide for incorporating Planetary Health, climate change and sustainability into nursing education programs. IMPLICATIONS FOR THE PROFESSION: Incorporating Planetary Health and climate change education into nursing programs has the potential to produce more environmentally conscious and socially responsible nurses. IMPACT: The absence of consensus on the essential knowledge and skills expected of nursing students has hindered the advancement of curricula and impacted educators' confidence in teaching Planetary Health and climate change. This study has resulted in a meticulously crafted framework of knowledge and skill statements that will be beneficial to educators, the future nursing workforce, and, ultimately, the individuals and communities whom nurses serve. REPORTING METHOD: This paper adheres to the Conducting and REporting DElphi Studies (CREDES) reporting guideline. PATIENT OR PUBLIC CONTRIBUTION: No patient or public contribution.

Published
2024

12. The relevance of rich club regions for functional outcome post-stroke is enhanced in women.

Author

Bonkhoff, AK, Schirmer, MD, Bretzner, M, Hong, S, Regenhardt, RW, Donahue, KL, Nardin, MJ, Dalca, AV, Giese, A-K, Etherton, MR, Hancock, BL, Mocking, SJT, McIntosh, EC, Attia, J, Cole, JW, Donatti, A, Griessenauer, CJ, Heitsch, L, Holmegaard, L, Jood, K, Jimenez-Conde, J, Kittner, SJ, Lemmens, R, Levi, CR, McDonough, CW, Meschia, JF, Phuah, C-L, Ropele, S, Rosand, J, Roquer, J, Rundek, T, Sacco, RL, Schmidt, R, Sharma, P, Slowik, A, Sousa, A, Stanne, TM, Strbian, D, Tatlisumak, T, Thijs, V, Vagal, A, Wasselius, J, Woo, D, Zand, R, McArdle, PF, Worrall, BB, Jern, C, Lindgren, AG, Maguire, J, Wu, O, Rost, NS, MRI-GENIE and GISCOME Investigators and the International Stroke Genetics Consortium, Bonkhoff, AK, Schirmer, MD, Bretzner, M, Hong, S, Regenhardt, RW, Donahue, KL, Nardin, MJ, Dalca, AV, Giese, A-K, Etherton, MR, Hancock, BL, Mocking, SJT, McIntosh, EC, Attia, J, Cole, JW, Donatti, A, Griessenauer, CJ, Heitsch, L, Holmegaard, L, Jood, K, Jimenez-Conde, J, Kittner, SJ, Lemmens, R, Levi, CR, McDonough, CW, Meschia, JF, Phuah, C-L, Ropele, S, Rosand, J, Roquer, J, Rundek, T, Sacco, RL, Schmidt, R, Sharma, P, Slowik, A, Sousa, A, Stanne, TM, Strbian, D, Tatlisumak, T, Thijs, V, Vagal, A, Wasselius, J, Woo, D, Zand, R, McArdle, PF, Worrall, BB, Jern, C, Lindgren, AG, Maguire, J, Wu, O, Rost, NS, and MRI-GENIE and GISCOME Investigators and the International Stroke Genetics Consortium

Abstract

This study aimed to investigate the influence of stroke lesions in predefined highly interconnected (rich-club) brain regions on functional outcome post-stroke, determine their spatial specificity and explore the effects of biological sex on their relevance. We analyzed MRI data recorded at index stroke and ~3-months modified Rankin Scale (mRS) data from patients with acute ischemic stroke enrolled in the multisite MRI-GENIE study. Spatially normalized structural stroke lesions were parcellated into 108 atlas-defined bilateral (sub)cortical brain regions. Unfavorable outcome (mRS > 2) was modeled in a Bayesian logistic regression framework. Effects of individual brain regions were captured as two compound effects for (i) six bilateral rich club and (ii) all further non-rich club regions. In spatial specificity analyses, we randomized the split into "rich club" and "non-rich club" regions and compared the effect of the actual rich club regions to the distribution of effects from 1000 combinations of six random regions. In sex-specific analyses, we introduced an additional hierarchical level in our model structure to compare male and female-specific rich club effects. A total of 822 patients (age: 64.7[15.0], 39% women) were analyzed. Rich club regions had substantial relevance in explaining unfavorable functional outcome (mean of posterior distribution: 0.08, area under the curve: 0.8). In particular, the rich club-combination had a higher relevance than 98.4% of random constellations. Rich club regions were substantially more important in explaining long-term outcome in women than in men. All in all, lesions in rich club regions were associated with increased odds of unfavorable outcome. These effects were spatially specific and more pronounced in women.

Published
2023

13. Nursing students’ genomics literacy: Basis for genomics nursing education course development

Author

Parviainen, A, Ward, LD, Halkoaho, A, Laing, B, Maguire, J, Palovaara, M, Mandysova, P, Bacungan, G, Mamungay, JJ, Sund, R, Mikkonen, S, Carlberg, C, Vehviläinen-Julkunen, K, Parviainen, A, Ward, LD, Halkoaho, A, Laing, B, Maguire, J, Palovaara, M, Mandysova, P, Bacungan, G, Mamungay, JJ, Sund, R, Mikkonen, S, Carlberg, C, and Vehviläinen-Julkunen, K

Abstract

This study aimed to investigate the genomics literacy of Finnish and Filipino nursing students as a basis for developing a genomics nursing education course. This is a cross-sectional online survey using the 31-item Genomic Nursing Concept Inventory, IBM SPSS version 27, and item-analysis. A total of 245 nursing students participated in the study; 75% reported that they had not completed any genetics-genomics courses. The GNCI scores ranged from 2 to 31 total correct answers out of a total possible score of 31. The GNCI mean score of the Finnish cohort (9.53; SD = 3.48; 36% correct) was significantly lower compared to the Filipino cohort (16.21; SD = 9.74, 58% correct). These results show that the genomics literacy of nursing students in Finland and the Philippines is weak, particularly in human genome homogeneity and genotype-phenotype association concepts. We recommend designing effective genetic and genomic educational programs and updating the nursing curricula.

Published
2023

14. Radiomics-Derived Brain Age Predicts Functional Outcome After Acute Ischemic Stroke.

Author

Bretzner, M, Bonkhoff, AK, Schirmer, MD, Hong, S, Dalca, A, Donahue, K, Giese, A-K, Etherton, MR, Rist, PM, Nardin, M, Regenhardt, RW, Leclerc, X, Lopes, R, Gautherot, M, Wang, C, Benavente, OR, Cole, JW, Donatti, A, Griessenauer, C, Heitsch, L, Holmegaard, L, Jood, K, Jimenez-Conde, J, Kittner, SJ, Lemmens, R, Levi, CR, McArdle, PF, McDonough, CW, Meschia, JF, Phuah, C-L, Rolfs, A, Ropele, S, Rosand, J, Roquer, J, Rundek, T, Sacco, RL, Schmidt, R, Sharma, P, Slowik, A, Sousa, A, Stanne, TM, Strbian, D, Tatlisumak, T, Thijs, V, Vagal, A, Wasselius, J, Woo, D, Wu, O, Zand, R, Worrall, BB, Maguire, J, Lindgren, AG, Jern, C, Golland, P, Kuchcinski, G, Rost, NS, Bretzner, M, Bonkhoff, AK, Schirmer, MD, Hong, S, Dalca, A, Donahue, K, Giese, A-K, Etherton, MR, Rist, PM, Nardin, M, Regenhardt, RW, Leclerc, X, Lopes, R, Gautherot, M, Wang, C, Benavente, OR, Cole, JW, Donatti, A, Griessenauer, C, Heitsch, L, Holmegaard, L, Jood, K, Jimenez-Conde, J, Kittner, SJ, Lemmens, R, Levi, CR, McArdle, PF, McDonough, CW, Meschia, JF, Phuah, C-L, Rolfs, A, Ropele, S, Rosand, J, Roquer, J, Rundek, T, Sacco, RL, Schmidt, R, Sharma, P, Slowik, A, Sousa, A, Stanne, TM, Strbian, D, Tatlisumak, T, Thijs, V, Vagal, A, Wasselius, J, Woo, D, Wu, O, Zand, R, Worrall, BB, Maguire, J, Lindgren, AG, Jern, C, Golland, P, Kuchcinski, G, and Rost, NS

Abstract

BACKGROUND AND OBJECTIVES: While chronological age is one of the most influential determinants of post-stroke outcomes, little is known of the impact of neuroimaging-derived biological "brain age". We hypothesized that radiomics analyses of T2-FLAIR images texture would provide brain age estimates and that advanced brain age of stroke patients will be associated with cardiovascular risk factors and worse functional outcomes. METHODS: We extracted radiomics from T2-FLAIR images acquired during acute stroke clinical evaluation. Brain age was determined from brain parenchyma radiomics using an ElasticNet linear regression model. Subsequently, relative brain age (RBA), which expresses brain age in comparison to chronological age-matched peers, was estimated. Finally, we built a linear regression model of RBA using clinical cardiovascular characteristics as inputs, and a logistic regression model of favorable functional outcomes taking RBA as input. RESULTS: We reviewed 4,163 patients from a large multisite ischemic stroke cohort (mean age=62.8 years, 42.0% females). T2-FLAIR radiomics predicted chronological ages (mean absolute error=6.9 years, r=0.81). After adjustment for covariates, RBA was higher and therefore described older-appearing brains in patients with hypertension, diabetes mellitus, a history of smoking, and a history of a prior stroke. In multivariate analyses, age, RBA, NIHSS, and a history of prior stroke were all significantly associated with functional outcome (respective adjusted Odds-Ratios: 0.58, 0.76, 0.48, 0.55; all p-values<0.001). Moreover, the negative effect of RBA on outcome was especially pronounced in minor strokes. DISCUSSION: T2-FLAIR radiomics can be used to predict brain age and derive RBA. Older appearing brains, characterized by a higher RBA, reflect cardiovascular risk factor accumulation and are linked to worse outcomes after stroke.

Published
2023

16. Tazarotene and Bexarotene Show Efficacy as In Vitro Therapeutic Agents in Multiple Sulfatase Deficiency.

Author

Schlotawa, L., Matysiak, K., Kettwig, M., Ahrens-Nicklas, R. C., Baud, M., Berulava, T., Brunetti-Pierri, N., Gagne, A., Herbst, Z. M., Maguire, J. A., Monfregola, J., Pena, T., Radhakrishnan, K., Schröder, S., Waxman, E. A., Ballabio, A., Dierks, T., Fischer, A., French, D. L., and Gelb, M. H.

Subjects
SULFATASES, LYSOSOMAL storage diseases, HIGH throughput screening (Drug development), NEURODEGENERATION, RESEARCH personnel, GLYCOGEN storage disease type II
Abstract

The article discusses the potential use of tazarotene and bexarotene as therapeutic agents for multiple sulfatase deficiency (MSD), an ultra-rare neurodegenerative lysosomal disorder. MSD is caused by mutations in the SUMF1 gene, resulting in impaired function of the formylglycine-generating enzyme (FGE) and reduced activity of cellular sulfatases. The researchers conducted a high-throughput screening assay and found that tazarotene and bexarotene increased sulfatase activities, improved cellular markers of disease, and normalized lysosomal size and position in MSD patient-derived cells. These findings suggest that these drugs could be repurposed as a therapy for MSD patients. [Extracted from the article]

Published
2023
Full Text
View/download PDF

20. Endothelin

Author

Davenport, A. P., Maguire, J. J., Starke, K., editor, Born, G. V. R., editor, Duckles, S. P., editor, Eichelbaum, M., editor, Ganten, D., editor, Hofmann, F., editor, Rosenthal, W., editor, Rubanyi, G., editor, Moncada, Salvador, editor, and Higgs, Annie, editor

Published
2006
Full Text
View/download PDF

21. Contribution of Common Genetic Variants to Risk of Early Onset Ischemic Stroke

Author

Jaworek, T, Xu, H, Gaynor, BJ, Cole, JW, Rannikmae, K, Stanne, TM, Tomppo, L, Abedi, V, Amouyel, P, Armstrong, ND, Attia, J, Bell, S, Benavente, OR, Boncoraglio, GB, Butterworth, A, Cervical Artery Dissections and Ischemic Stroke Patients (CADSIP) Consortium, Carcel-Marquez, J, Chen, Z, Chong, M, Cruchaga, C, Cushman, M, Danesh, J, Debette, S, Duggan, DJ, Durda, JP, Engstrom, G, Enzinger, C, Faul, JD, Fecteau, NS, Fernandez-Cadenas, I, Gieger, C, Giese, A-K, Grewal, RP, Grittner, U, Havulinna, AS, Heitsch, L, Hochberg, MC, Holliday, E, Hu, J, Ilinca, A, INVENT Consortium, Irvin, MR, Jackson, RD, Jacob, MA, Janssen, RR, Jimenez-Conde, J, Johnson, JA, Kamatani, Y, Kardia, SL, Koido, M, Kubo, M, Lange, L, Lee, J-M, Lemmens, R, Levi, CR, Li, J, Li, L, Lin, K, Lopez, H, Luke, S, Maguire, J, McArdle, PF, McDonough, CW, Meschia, JF, Metso, T, Muller-Nurasyid, M, O'Connor, TD, O'Donnell, M, Peddareddygari, LR, Pera, J, Perry, JA, Peters, A, Putaala, J, Ray, D, Rexrode, K, Ribases, M, Rosand, J, Rothwell, PM, Rundek, T, Ryan, KA, Sacco, RL, Salomaa, V, Sanchez-Mora, C, Schmidt, R, Sharma, P, Slowik, A, Smith, JA, Smith, NL, Wassertheil-Smoller, S, Soederholm, M, Stine, OC, Strbian, D, Sudlow, CL, Tatlisumak, T, Terao, C, Thijs, V, Torres-Aguila, NP, Tregouet, D-A, Tuladhar, AM, Veldink, JH, Walters, RG, Weir, DR, Woo, D, Worrall, BB, Hong, CC, Ross, O, Zand, R, Leeuw, F-ED, Lindgren, AG, Pare, G, Anderson, CD, Markus, HS, Jern, C, Malik, R, Dichgans, M, Mitchell, BD, Kittner, SJ, and Early Onset Stroke Genetics Consortium of the International Stroke Genetics Consortium (ISGC)

Subjects
Neurology & Neurosurgery, 1103 Clinical Sciences, 1109 Neurosciences, 1702 Cognitive Sciences
Abstract

BACKGROUND AND OBJECTIVES: Current genome-wide association studies of ischemic stroke have focused primarily on late onset disease. As a complement to these studies, we sought to identifythe contribution of common genetic variants to risk of early onset ischemic stroke. METHODS: We performed a meta-analysis of genome-wide association studies of early onset stroke (EOS), ages 18-59, using individual level data or summary statistics in 16,730 cases and 599,237 non-stroke controls obtained across 48 different studies. We further compared effect sizes at associated loci between EOS and late onset stroke (LOS) and compared polygenic risk scores for venous thromboembolism between EOS and LOS. RESULTS: We observed genome-wide significant associations of EOS with two variants in ABO, a known stroke locus. These variants tag blood subgroups O1 and A1, and the effect sizes of both variants were significantly larger in EOS compared to LOS. The odds ratio (OR) for rs529565, tagging O1, 0.88 (95% CI: 0.85-0.91) in EOS vs 0.96 (95% CI: 0.92-1.00) in LOS, and the OR for rs635634, tagging A1, was 1.16 (1.11-1.21) for EOS vs 1.05 (0.99-1.11) in LOS; p-values for interaction = 0.001 and 0.005, respectively. Using polygenic risk scores, we observed that greater genetic risk for venous thromboembolism, another prothrombotic condition, was more strongly associated with EOS compared to LOS (p=0.008). DISCUSSION: The ABO locus, genetically predicted blood group A, and higher genetic propensity for venous thrombosis are more strongly associated with EOS than with LOS, supporting a stronger role of prothrombotic factors in EOS.

Published
2022

27. Sex-specific lesion pattern of functional outcomes after stroke

Author

Bonkhoff, AK, Bretzner, M, Hong, S, Schirmer, MD, Cohen, A, Regenhardt, RW, Donahue, KL, Nardin, MJ, Dalca, A, Giese, A-K, Etherton, MR, Hancock, BL, Mocking, SJT, McIntosh, EC, Attia, J, Benavente, OR, Bevan, S, Cole, JW, Donatti, A, Griessenauer, CJ, Heitsch, L, Holmegaard, L, Jood, K, Jimenez-Conde, J, Kittner, SJ, Lemmens, R, Levi, CR, McDonough, CW, Meschia, JF, Phuah, C-L, Rolfs, A, Ropele, S, Rosand, J, Roquer, J, Rundek, T, Sacco, RL, Schmidt, R, Sharma, P, Slowik, A, Soderholm, M, Sousa, A, Stanne, TM, Strbian, D, Tatlisumak, T, Thijs, V, Vagal, A, Wasselius, J, Woo, D, Zand, R, McArdle, PF, Worrall, BB, Jern, C, Lindgren, AG, Maguire, J, Fox, MD, Bzdok, D, Wu, O, Rost, NS, Bonkhoff, AK, Bretzner, M, Hong, S, Schirmer, MD, Cohen, A, Regenhardt, RW, Donahue, KL, Nardin, MJ, Dalca, A, Giese, A-K, Etherton, MR, Hancock, BL, Mocking, SJT, McIntosh, EC, Attia, J, Benavente, OR, Bevan, S, Cole, JW, Donatti, A, Griessenauer, CJ, Heitsch, L, Holmegaard, L, Jood, K, Jimenez-Conde, J, Kittner, SJ, Lemmens, R, Levi, CR, McDonough, CW, Meschia, JF, Phuah, C-L, Rolfs, A, Ropele, S, Rosand, J, Roquer, J, Rundek, T, Sacco, RL, Schmidt, R, Sharma, P, Slowik, A, Soderholm, M, Sousa, A, Stanne, TM, Strbian, D, Tatlisumak, T, Thijs, V, Vagal, A, Wasselius, J, Woo, D, Zand, R, McArdle, PF, Worrall, BB, Jern, C, Lindgren, AG, Maguire, J, Fox, MD, Bzdok, D, Wu, O, and Rost, NS

Abstract

Stroke represents a considerable burden of disease for both men and women. However, a growing body of literature suggests clinically relevant sex differences in the underlying causes, presentations and outcomes of acute ischaemic stroke. In a recent study, we reported sex divergences in lesion topographies: specific to women, acute stroke severity was linked to lesions in the left-hemispheric posterior circulation. We here determined whether these sex-specific brain manifestations also affect long-term outcomes. We relied on 822 acute ischaemic patients [age: 64.7 (15.0) years, 39% women] originating from the multi-centre MRI-GENIE study to model unfavourable outcomes (modified Rankin Scale >2) based on acute neuroimaging data in a Bayesian hierarchical framework. Lesions encompassing bilateral subcortical nuclei and left-lateralized regions in proximity to the insula explained outcomes across men and women (area under the curve = 0.81). A pattern of left-hemispheric posterior circulation brain regions, combining left hippocampus, precuneus, fusiform and lingual gyrus, occipital pole and latero-occipital cortex, showed a substantially higher relevance in explaining functional outcomes in women compared to men [mean difference of Bayesian posterior distributions (men - women) = -0.295 (90% highest posterior density interval = -0.556 to -0.068)]. Once validated in prospective studies, our findings may motivate a sex-specific approach to clinical stroke management and hold the promise of enhancing outcomes on a population level.

Published
2022

28. Association of Stroke Lesion Pattern and White Matter Hyperintensity Burden With Stroke Severity and Outcome.

Author

Bonkhoff, AK, Hong, S, Bretzner, M, Schirmer, MD, Regenhardt, RW, Arsava, EM, Donahue, K, Nardin, M, Dalca, A, Giese, A-K, Etherton, MR, Hancock, BL, Mocking, SJT, McIntosh, E, Attia, J, Benavente, O, Cole, JW, Donatti, A, Griessenauer, C, Heitsch, L, Holmegaard, L, Jood, K, Jimenez-Conde, J, Kittner, S, Lemmens, R, Levi, C, McDonough, CW, Meschia, J, Phuah, C-L, Rolfs, A, Ropele, S, Rosand, J, Roquer, J, Rundek, T, Sacco, RL, Schmidt, R, Sharma, P, Slowik, A, Soederholm, M, Sousa, A, Stanne, TM, Strbian, D, Tatlisumak, T, Thijs, V, Vagal, A, Wasselius, J, Woo, D, Zand, R, McArdle, P, Worrall, BB, Jern, C, Lindgren, AG, Maguire, J, Golland, P, Bzdok, D, Wu, O, Rost, NS, Bonkhoff, AK, Hong, S, Bretzner, M, Schirmer, MD, Regenhardt, RW, Arsava, EM, Donahue, K, Nardin, M, Dalca, A, Giese, A-K, Etherton, MR, Hancock, BL, Mocking, SJT, McIntosh, E, Attia, J, Benavente, O, Cole, JW, Donatti, A, Griessenauer, C, Heitsch, L, Holmegaard, L, Jood, K, Jimenez-Conde, J, Kittner, S, Lemmens, R, Levi, C, McDonough, CW, Meschia, J, Phuah, C-L, Rolfs, A, Ropele, S, Rosand, J, Roquer, J, Rundek, T, Sacco, RL, Schmidt, R, Sharma, P, Slowik, A, Soederholm, M, Sousa, A, Stanne, TM, Strbian, D, Tatlisumak, T, Thijs, V, Vagal, A, Wasselius, J, Woo, D, Zand, R, McArdle, P, Worrall, BB, Jern, C, Lindgren, AG, Maguire, J, Golland, P, Bzdok, D, Wu, O, and Rost, NS

Abstract

BACKGROUND AND OBJECTIVES: To examine whether high white matter hyperintensity (WMH) burden is associated with greater stroke severity and worse functional outcomes in lesion pattern-specific ways. METHODS: MR neuroimaging and NIH Stroke Scale data at index stroke and the modified Rankin Scale (mRS) score at 3-6 months after stroke were obtained from the MRI-Genetics Interface Exploration study of patients with acute ischemic stroke (AIS). Individual WMH volume was automatically derived from fluid-attenuated inversion recovery images. Stroke lesions were automatically segmented from diffusion-weighted imaging (DWI) images, parcellated into atlas-defined brain regions and further condensed to 10 lesion patterns via machine learning-based dimensionality reduction. Stroke lesion effects on AIS severity and unfavorable outcomes (mRS score >2) were modeled within purpose-built Bayesian linear and logistic regression frameworks. Interaction effects between stroke lesions and a high vs low WMH burden were integrated via hierarchical model structures. Models were adjusted for age, age2, sex, total DWI lesion and WMH volumes, and comorbidities. Data were split into derivation and validation cohorts. RESULTS: A total of 928 patients with AIS contributed to acute stroke severity analyses (age: 64.8 [14.5] years, 40% women) and 698 patients to long-term functional outcome analyses (age: 65.9 [14.7] years, 41% women). Stroke severity was mainly explained by lesions focused on bilateral subcortical and left hemispherically pronounced cortical regions across patients with both a high and low WMH burden. Lesions centered on left-hemispheric insular, opercular, and inferior frontal regions and lesions affecting right-hemispheric temporoparietal regions had more pronounced effects on stroke severity in case of high compared with low WMH burden. Unfavorable outcomes were predominantly explained by lesions in bilateral subcortical regions. In difference to the lesion location-specific

Published
2022

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

Author

Mishra, A, Malik, R, Hachiya, T, Jurgenson, T, Namba, S, Posner, DC, Kamanu, FK, Koido, M, Le Grand, Q, Shi, M, He, Y, Georgakis, MK, Caro, I, Krebs, K, Liaw, Y-C, Vaura, FC, Lin, K, Winsvold, BS, Srinivasasainagendra, V, Parodi, L, Bae, H-J, Chauhan, G, Chong, MR, Tomppo, L, Akinyemi, R, Roshchupkin, GV, Habib, N, Jee, YH, Thomassen, JQ, Abedi, V, Carcel-Marquez, J, Nygaard, M, Leonard, HL, Yang, C, Yonova-Doing, E, Knol, MJ, Lewis, AJ, Judy, RL, Ago, T, Amouyel, P, Armstrong, ND, Bakker, MK, Bartz, TM, Bennett, DA, Bis, JC, Bordes, C, Borte, S, Cain, A, Ridker, PM, Cho, K, Chen, Z, Cruchaga, C, Cole, JW, de Jager, PL, de Cid, R, Endres, M, Ferreira, LE, Geerlings, MI, Gasca, NC, Gudnason, V, Hata, J, He, J, Heath, AK, Ho, Y-L, Havulinna, AS, Hopewell, JC, Hyacinth, HI, Inouye, M, Jacob, MA, Jeon, CE, Jern, C, Kamouchi, M, Keene, KL, Kitazono, T, Kittner, SJ, Konuma, T, Kumar, A, Lacaze, P, Launer, LJ, Lee, K-J, Lepik, K, Li, J, Li, L, Manichaikul, A, Markus, HS, Marston, NA, Meitinger, T, Mitchell, BD, Montellano, FA, Morisaki, T, Mosley, TH, Nalls, MA, Nordestgaard, BG, O'Donnell, MJ, Okada, Y, Onland-Moret, NC, Ovbiagele, B, Peters, A, Psaty, BM, Rich, SS, Rosand, J, Sabatine, MS, Sacco, RL, Saleheen, D, Sandset, EC, Salomaa, V, Sargurupremraj, M, Sasaki, M, Satizabal, CL, Schmidt, CO, Shimizu, A, Smith, NL, Sloane, KL, Sutoh, Y, Sun, YV, Tanno, K, Tiedt, S, Tatlisumak, T, Torres-Aguila, NP, Tiwari, HK, Tregouet, D-A, Trompet, S, Tuladhar, AM, Tybjaerg-Hansen, A, van Vugt, M, Vibo, R, Verma, SS, Wiggins, KL, Wennberg, P, Woo, D, Wilson, PWF, Xu, H, Yang, Q, Yoon, K, Lee, J-M, Cheng, Y-C, Meschia, JF, Chen, WM, Sale, MM, Zonderman, AB, Evans, MK, Wilson, JG, Correa, A, Traylor, M, Lewis, CM, Carty, CL, Reiner, A, Haessler, J, Langefeld, CD, Gottesman, RF, Yaffe, K, Liu, YM, Kooperberg, C, Lange, LA, Furie, KL, Arnett, DK, Benavente, OR, Grewal, RP, Peddareddygari, LR, Hveem, K, Lindstrom, S, Wang, L, Smith, EN, Gordon, W, van Hylckama Vlieg, A, de Andrade, M, Brody, JA, Pattee, JW, Brumpton, BM, Suchon, P, Chen, M-H, Frazer, KA, Turman, C, Germain, M, MacDonald, J, Braekkan, SK, Armasu, SM, Pankratz, N, Jackson, RD, Nielsen, JB, Giulianini, F, Puurunen, MK, Ibrahim, M, Heckbert, SR, Bammler, TK, McCauley, BM, Taylor, KD, Pankow, JS, Reiner, AP, Gabrielsen, ME, Deleuze, J-F, O'Donnell, CJ, Kim, J, McKnight, B, Kraft, P, Hansen, J-B, Rosendaal, FR, Heit, JA, Tang, W, Morange, P-E, Johnson, AD, Kabrhel, C, van Dijk, EJ, Koudstaal, PJ, Luijckx, G-J, Nederkoorn, PJ, van Oostenbrugge, RJ, Visser, MC, Wermer, MJH, Kappelle, LJ, Esko, T, Metspalu, A, Magi, R, Nelis, M, Irvin, MR, de Leeuw, F-E, Levi, CR, Maguire, J, Jimenez-Conde, J, Sharma, P, Sudlow, CLM, Rannikmae, K, Schmidt, R, Slowik, A, Pera, J, Thijs, VNS, Lindgren, AG, Ilinca, A, Melander, O, Engstrom, G, Rexrode, KM, Rothwell, PM, Stanne, TM, Johnson, JA, Danesh, J, Butterworth, AS, Heitsch, L, Boncoraglio, GB, Kubo, M, Pezzini, A, Rolfs, A, Giese, A-K, Weir, D, Ross, OA, Lemmons, R, Soderholm, M, Cushman, M, Jood, K, McDonough, CW, Bell, S, Linkohr, B, Lee, T-H, Putaala, J, Anderson, CD, Lopez, OL, Jian, X, Schminke, U, Cullell, N, Delgado, P, Ibanez, L, Krupinski, J, Lioutas, V, Matsuda, K, Montaner, J, Muino, E, Roquer, J, Sarnowski, C, Sattar, N, Sibolt, G, Teumer, A, Rutten-Jacobs, L, Kanai, M, Gretarsdottir, S, Rost, NS, Yusuf, S, Almgren, P, Ay, H, Bevan, S, Brown, RD, Carrera, C, Buring, JE, Chen, W-M, Cotlarciuc, I, de Bakker, PIW, DeStefano, AL, den Hoed, M, Duan, Q, Engelter, ST, Falcone, GJ, Gustafsson, S, Hassan, A, Holliday, EG, Howard, G, Hsu, F-C, Ingelsson, E, Harris, TB, Kissela, BM, Kleindorfer, DO, Langenberg, C, Lemmens, R, Leys, D, Lin, W-Y, Lorentzen, E, Magnusson, PK, McArdle, PF, Pulit, SL, Rice, K, Sakaue, S, Sapkota, BR, Tanislav, C, Thorleifsson, G, Thorsteinsdottir, U, Tzourio, C, van Duijn, CM, Walters, M, Wareham, NJ, Amin, N, Aparicio, HJ, Attia, J, Beiser, AS, Berr, C, Bustamante, M, Caso, V, Choi, SH, Chowhan, A, Dartigues, J-F, Delavaran, H, Dorr, M, Ford, I, Gurpreet, WS, Hamsten, A, Hozawa, A, Ingelsson, M, Iwasaki, M, Kaffashian, S, Kalra, L, Kjartansson, O, Kloss, M, Labovitz, DL, Laurie, CC, Lind, L, Lindgren, CM, Makoto, H, Minegishi, N, Morris, AP, Muller-Nurasyid, M, Norrving, B, Ogishima, S, Parati, EA, Pedersen, NL, Perola, M, Jousilahti, P, Pileggi, S, Rabionet, R, Riba-Llena, I, Ribases, M, Romero, JR, Rudd, AG, Sarin, A-P, Sarju, R, Satoh, M, Sawada, N, Sigurdsson, A, Smith, A, Stine, OC, Stott, DJ, Strauch, K, Takai, T, Tanaka, H, Touze, E, Tsugane, S, Uitterlinden, AG, Valdimarsson, EM, van der Lee, SJ, Wakai, K, Williams, SR, Wolfe, CDA, Wong, Q, Yamaji, T, Sanghera, DK, Stefansson, K, Martinez-Majander, N, Sobue, K, Soriano-Tarraga, C, Volzke, H, Akpa, O, Sarfo, FS, Akpalu, A, Obiako, R, Wahab, K, Osaigbovo, G, Owolabi, L, Komolafe, M, Jenkins, C, Arulogun, O, Ogbole, G, Adeoye, AM, Akinyemi, J, Agunloye, A, Fakunle, AG, Uvere, E, Olalere, A, Adebajo, OJ, Chen, J, Clarke, R, Collins, R, Guo, Y, Wang, C, Lv, J, Peto, R, Chen, Y, Fairhurst-Hunter, Z, Hill, M, Pozarickij, A, Schmidt, D, Stevens, B, Turnbull, I, Yu, C, Nagai, A, Murakami, Y, Shiroma, EJ, Sigurdsson, S, Ghanbari, M, Boerwinkle, E, Fongang, B, Wang, R, Ikram, MK, Volker, U, de Laat, KF, van Norden, AGW, de Kort, PL, Vermeer, SE, Brouwers, PJAM, Gons, RAR, den Heijer, T, van Dijk, GW, van Rooij, FGW, Aamodt, AH, Skogholt, AH, Willer, CJ, Heuch, I, Hagen, K, Fritsche, LG, Pedersen, LM, Ellekjaer, H, Zhou, W, Martinsen, AE, Kristoffersen, ES, Thomas, LF, Kleinschnitz, C, Frantz, S, Ungethum, K, Gallego-Fabrega, C, Lledos, M, Llucia-Carol, L, Sobrino, T, Campos, F, Castillo, J, Freijo, M, Arenillas, JF, Obach, V, Alvarez-Sabin, J, Molina, CA, Ribo, M, Munoz-Narbona, L, Lopez-Cancio, E, Millan, M, Diaz-Navarro, R, Vives-Bauza, C, Serrano-Heras, G, Segura, T, Dhar, R, Delgado-Mederos, R, Prats-Sanchez, L, Camps-Renom, P, Blay, N, Sumoy, L, Marti-Fabregas, J, Schnohr, P, Jensen, GB, Benn, M, Afzal, S, Kamstrup, PR, van Setten, J, van der Laan, SW, Vonk, JMJ, Kim, B-J, Curtze, S, Tiainen, M, Kinnunen, J, Menon, V, Sung, YJ, Saillour-Glenisson, F, Gravel, S, Millwood, IY, Gieger, C, Ninomiya, T, Grabe, HJ, Jukema, JW, Rissanen, IL, Strbian, D, Kim, YJ, Chen, P-H, Mayerhofer, E, Howson, JMM, Adams, H, Wassertheil-Smoller, S, Christensen, K, Ikram, MA, Rundek, T, Worrall, BB, Lathrop, GM, Riaz, M, Simonsick, EM, Korv, J, Franca, PHC, Zand, R, Prasad, K, Frikke-Schmidt, R, Liman, T, Haeusler, KG, Ruigrok, YM, Heuschmann, PU, Longstreth, WT, Jung, KJ, Bastarache, L, Pare, G, Damrauer, SM, Chasman, DI, Rotter, JI, Zwart, J-A, Niiranen, TJ, Fornage, M, Liaw, Y-P, Seshadri, S, Fernandez-Cadenas, I, Walters, RG, Ruff, CT, Owolabi, MO, Huffman, JE, Milani, L, Kamatani, Y, Dichgans, M, Debette, S, Mishra, A, Malik, R, Hachiya, T, Jurgenson, T, Namba, S, Posner, DC, Kamanu, FK, Koido, M, Le Grand, Q, Shi, M, He, Y, Georgakis, MK, Caro, I, Krebs, K, Liaw, Y-C, Vaura, FC, Lin, K, Winsvold, BS, Srinivasasainagendra, V, Parodi, L, Bae, H-J, Chauhan, G, Chong, MR, Tomppo, L, Akinyemi, R, Roshchupkin, GV, Habib, N, Jee, YH, Thomassen, JQ, Abedi, V, Carcel-Marquez, J, Nygaard, M, Leonard, HL, Yang, C, Yonova-Doing, E, Knol, MJ, Lewis, AJ, Judy, RL, Ago, T, Amouyel, P, Armstrong, ND, Bakker, MK, Bartz, TM, Bennett, DA, Bis, JC, Bordes, C, Borte, S, Cain, A, Ridker, PM, Cho, K, Chen, Z, Cruchaga, C, Cole, JW, de Jager, PL, de Cid, R, Endres, M, Ferreira, LE, Geerlings, MI, Gasca, NC, Gudnason, V, Hata, J, He, J, Heath, AK, Ho, Y-L, Havulinna, AS, Hopewell, JC, Hyacinth, HI, Inouye, M, Jacob, MA, Jeon, CE, Jern, C, Kamouchi, M, Keene, KL, Kitazono, T, Kittner, SJ, Konuma, T, Kumar, A, Lacaze, P, Launer, LJ, Lee, K-J, Lepik, K, Li, J, Li, L, Manichaikul, A, Markus, HS, Marston, NA, Meitinger, T, Mitchell, BD, Montellano, FA, Morisaki, T, Mosley, TH, Nalls, MA, Nordestgaard, BG, O'Donnell, MJ, Okada, Y, Onland-Moret, NC, Ovbiagele, B, Peters, A, Psaty, BM, Rich, SS, Rosand, J, Sabatine, MS, Sacco, RL, Saleheen, D, Sandset, EC, Salomaa, V, Sargurupremraj, M, Sasaki, M, Satizabal, CL, Schmidt, CO, Shimizu, A, Smith, NL, Sloane, KL, Sutoh, Y, Sun, YV, Tanno, K, Tiedt, S, Tatlisumak, T, Torres-Aguila, NP, Tiwari, HK, Tregouet, D-A, Trompet, S, Tuladhar, AM, Tybjaerg-Hansen, A, van Vugt, M, Vibo, R, Verma, SS, Wiggins, KL, Wennberg, P, Woo, D, Wilson, PWF, Xu, H, Yang, Q, Yoon, K, Lee, J-M, Cheng, Y-C, Meschia, JF, Chen, WM, Sale, MM, Zonderman, AB, Evans, MK, Wilson, JG, Correa, A, Traylor, M, Lewis, CM, Carty, CL, Reiner, A, Haessler, J, Langefeld, CD, Gottesman, RF, Yaffe, K, Liu, YM, Kooperberg, C, Lange, LA, Furie, KL, Arnett, DK, Benavente, OR, Grewal, RP, Peddareddygari, LR, Hveem, K, Lindstrom, S, Wang, L, Smith, EN, Gordon, W, van Hylckama Vlieg, A, de Andrade, M, Brody, JA, Pattee, JW, Brumpton, BM, Suchon, P, Chen, M-H, Frazer, KA, Turman, C, Germain, M, MacDonald, J, Braekkan, SK, Armasu, SM, Pankratz, N, Jackson, RD, Nielsen, JB, Giulianini, F, Puurunen, MK, Ibrahim, M, Heckbert, SR, Bammler, TK, McCauley, BM, Taylor, KD, Pankow, JS, Reiner, AP, Gabrielsen, ME, Deleuze, J-F, O'Donnell, CJ, Kim, J, McKnight, B, Kraft, P, Hansen, J-B, Rosendaal, FR, Heit, JA, Tang, W, Morange, P-E, Johnson, AD, Kabrhel, C, van Dijk, EJ, Koudstaal, PJ, Luijckx, G-J, Nederkoorn, PJ, van Oostenbrugge, RJ, Visser, MC, Wermer, MJH, Kappelle, LJ, Esko, T, Metspalu, A, Magi, R, Nelis, M, Irvin, MR, de Leeuw, F-E, Levi, CR, Maguire, J, Jimenez-Conde, J, Sharma, P, Sudlow, CLM, Rannikmae, K, Schmidt, R, Slowik, A, Pera, J, Thijs, VNS, Lindgren, AG, Ilinca, A, Melander, O, Engstrom, G, Rexrode, KM, Rothwell, PM, Stanne, TM, Johnson, JA, Danesh, J, Butterworth, AS, Heitsch, L, Boncoraglio, GB, Kubo, M, Pezzini, A, Rolfs, A, Giese, A-K, Weir, D, Ross, OA, Lemmons, R, Soderholm, M, Cushman, M, Jood, K, McDonough, CW, Bell, S, Linkohr, B, Lee, T-H, Putaala, J, Anderson, CD, Lopez, OL, Jian, X, Schminke, U, Cullell, N, Delgado, P, Ibanez, L, Krupinski, J, Lioutas, V, Matsuda, K, Montaner, J, Muino, E, Roquer, J, Sarnowski, C, Sattar, N, Sibolt, G, Teumer, A, Rutten-Jacobs, L, Kanai, M, Gretarsdottir, S, Rost, NS, Yusuf, S, Almgren, P, Ay, H, Bevan, S, Brown, RD, Carrera, C, Buring, JE, Chen, W-M, Cotlarciuc, I, de Bakker, PIW, DeStefano, AL, den Hoed, M, Duan, Q, Engelter, ST, Falcone, GJ, Gustafsson, S, Hassan, A, Holliday, EG, Howard, G, Hsu, F-C, Ingelsson, E, Harris, TB, Kissela, BM, Kleindorfer, DO, Langenberg, C, Lemmens, R, Leys, D, Lin, W-Y, Lorentzen, E, Magnusson, PK, McArdle, PF, Pulit, SL, Rice, K, Sakaue, S, Sapkota, BR, Tanislav, C, Thorleifsson, G, Thorsteinsdottir, U, Tzourio, C, van Duijn, CM, Walters, M, Wareham, NJ, Amin, N, Aparicio, HJ, Attia, J, Beiser, AS, Berr, C, Bustamante, M, Caso, V, Choi, SH, Chowhan, A, Dartigues, J-F, Delavaran, H, Dorr, M, Ford, I, Gurpreet, WS, Hamsten, A, Hozawa, A, Ingelsson, M, Iwasaki, M, Kaffashian, S, Kalra, L, Kjartansson, O, Kloss, M, Labovitz, DL, Laurie, CC, Lind, L, Lindgren, CM, Makoto, H, Minegishi, N, Morris, AP, Muller-Nurasyid, M, Norrving, B, Ogishima, S, Parati, EA, Pedersen, NL, Perola, M, Jousilahti, P, Pileggi, S, Rabionet, R, Riba-Llena, I, Ribases, M, Romero, JR, Rudd, AG, Sarin, A-P, Sarju, R, Satoh, M, Sawada, N, Sigurdsson, A, Smith, A, Stine, OC, Stott, DJ, Strauch, K, Takai, T, Tanaka, H, Touze, E, Tsugane, S, Uitterlinden, AG, Valdimarsson, EM, van der Lee, SJ, Wakai, K, Williams, SR, Wolfe, CDA, Wong, Q, Yamaji, T, Sanghera, DK, Stefansson, K, Martinez-Majander, N, Sobue, K, Soriano-Tarraga, C, Volzke, H, Akpa, O, Sarfo, FS, Akpalu, A, Obiako, R, Wahab, K, Osaigbovo, G, Owolabi, L, Komolafe, M, Jenkins, C, Arulogun, O, Ogbole, G, Adeoye, AM, Akinyemi, J, Agunloye, A, Fakunle, AG, Uvere, E, Olalere, A, Adebajo, OJ, Chen, J, Clarke, R, Collins, R, Guo, Y, Wang, C, Lv, J, Peto, R, Chen, Y, Fairhurst-Hunter, Z, Hill, M, Pozarickij, A, Schmidt, D, Stevens, B, Turnbull, I, Yu, C, Nagai, A, Murakami, Y, Shiroma, EJ, Sigurdsson, S, Ghanbari, M, Boerwinkle, E, Fongang, B, Wang, R, Ikram, MK, Volker, U, de Laat, KF, van Norden, AGW, de Kort, PL, Vermeer, SE, Brouwers, PJAM, Gons, RAR, den Heijer, T, van Dijk, GW, van Rooij, FGW, Aamodt, AH, Skogholt, AH, Willer, CJ, Heuch, I, Hagen, K, Fritsche, LG, Pedersen, LM, Ellekjaer, H, Zhou, W, Martinsen, AE, Kristoffersen, ES, Thomas, LF, Kleinschnitz, C, Frantz, S, Ungethum, K, Gallego-Fabrega, C, Lledos, M, Llucia-Carol, L, Sobrino, T, Campos, F, Castillo, J, Freijo, M, Arenillas, JF, Obach, V, Alvarez-Sabin, J, Molina, CA, Ribo, M, Munoz-Narbona, L, Lopez-Cancio, E, Millan, M, Diaz-Navarro, R, Vives-Bauza, C, Serrano-Heras, G, Segura, T, Dhar, R, Delgado-Mederos, R, Prats-Sanchez, L, Camps-Renom, P, Blay, N, Sumoy, L, Marti-Fabregas, J, Schnohr, P, Jensen, GB, Benn, M, Afzal, S, Kamstrup, PR, van Setten, J, van der Laan, SW, Vonk, JMJ, Kim, B-J, Curtze, S, Tiainen, M, Kinnunen, J, Menon, V, Sung, YJ, Saillour-Glenisson, F, Gravel, S, Millwood, IY, Gieger, C, Ninomiya, T, Grabe, HJ, Jukema, JW, Rissanen, IL, Strbian, D, Kim, YJ, Chen, P-H, Mayerhofer, E, Howson, JMM, Adams, H, Wassertheil-Smoller, S, Christensen, K, Ikram, MA, Rundek, T, Worrall, BB, Lathrop, GM, Riaz, M, Simonsick, EM, Korv, J, Franca, PHC, Zand, R, Prasad, K, Frikke-Schmidt, R, Liman, T, Haeusler, KG, Ruigrok, YM, Heuschmann, PU, Longstreth, WT, Jung, KJ, Bastarache, L, Pare, G, Damrauer, SM, Chasman, DI, Rotter, JI, Zwart, J-A, Niiranen, TJ, Fornage, M, Liaw, Y-P, Seshadri, S, Fernandez-Cadenas, I, Walters, RG, Ruff, CT, Owolabi, MO, Huffman, JE, Milani, L, Kamatani, Y, Dichgans, M, and Debette, S

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

30. Deep profiling of multiple ischemic lesions in a large, multi-center cohort: Frequency, spatial distribution, and associations to clinical characteristics

Author

Bonkhoff, AK, Ullberg, T, Bretzner, M, Hong, S, Schirmer, MD, Regenhardt, RW, Donahue, KL, Nardin, MJ, Dalca, A, Giese, A-K, Etherton, MR, Hancock, BL, Mocking, SJT, McIntosh, EC, Attia, J, Cole, JW, Donatti, A, Griessenauer, CJ, Heitsch, L, Holmegaard, L, Jood, K, Jimenez-Conde, J, Kittner, SJ, Lemmens, R, Levi, CR, McDonough, CW, Meschia, JF, Phuah, C-L, Ropele, S, Rosand, J, Roquer, J, Rundek, T, Sacco, RL, Schmidt, R, Sharma, P, Slowik, A, Sousa, A, Stanne, TM, Strbian, D, Tatlisumak, T, Thijs, V, Vagal, A, Woo, D, Zand, R, McArdle, PF, Worrall, BB, Jern, C, Lindgren, AG, Maguire, J, Wu, O, Frid, P, Rost, NS, Wasselius, J, Bonkhoff, AK, Ullberg, T, Bretzner, M, Hong, S, Schirmer, MD, Regenhardt, RW, Donahue, KL, Nardin, MJ, Dalca, A, Giese, A-K, Etherton, MR, Hancock, BL, Mocking, SJT, McIntosh, EC, Attia, J, Cole, JW, Donatti, A, Griessenauer, CJ, Heitsch, L, Holmegaard, L, Jood, K, Jimenez-Conde, J, Kittner, SJ, Lemmens, R, Levi, CR, McDonough, CW, Meschia, JF, Phuah, C-L, Ropele, S, Rosand, J, Roquer, J, Rundek, T, Sacco, RL, Schmidt, R, Sharma, P, Slowik, A, Sousa, A, Stanne, TM, Strbian, D, Tatlisumak, T, Thijs, V, Vagal, A, Woo, D, Zand, R, McArdle, PF, Worrall, BB, Jern, C, Lindgren, AG, Maguire, J, Wu, O, Frid, P, Rost, NS, and Wasselius, J

Abstract

BACKGROUND PURPOSE: A substantial number of patients with acute ischemic stroke (AIS) experience multiple acute lesions (MAL). We here aimed to scrutinize MAL in a large radiologically deep-phenotyped cohort. MATERIALS AND METHODS: Analyses relied upon imaging and clinical data from the international MRI-GENIE study. Imaging data comprised both Fluid-attenuated inversion recovery (FLAIR) for white matter hyperintensity (WMH) burden estimation and diffusion-weighted imaging (DWI) sequences for the assessment of acute stroke lesions. The initial step featured the systematic evaluation of occurrences of MAL within one and several vascular supply territories. Associations between MAL and important imaging and clinical characteristics were subsequently determined. The interaction effect between single and multiple lesion status and lesion volume was estimated by means of Bayesian hierarchical regression modeling for both stroke severity and functional outcome. RESULTS: We analyzed 2,466 patients (age = 63.4 ± 14.8, 39% women), 49.7% of which presented with a single lesion. Another 37.4% experienced MAL in a single vascular territory, while 12.9% featured lesions in multiple vascular territories. Within most territories, MAL occurred as frequently as single lesions (ratio ∼1:1). Only the brainstem region comprised fewer patients with MAL (ratio 1:4). Patients with MAL presented with a significantly higher lesion volume and acute NIHSS (7.7 vs. 1.7 ml and 4 vs. 3, p FDR < 0.001). In contrast, patients with a single lesion were characterized by a significantly higher WMH burden (6.1 vs. 5.3 ml, p FDR = 0.048). Functional outcome did not differ significantly between patients with single versus multiple lesions. Bayesian analyses suggested that the association between lesion volume and stroke severity between single and multiple lesions was the same in case of anterior circulation stroke. In case of posterior circulation stroke, lesion volume was linked to a higher NIHSS only

Published
2022

31. 2022 ASAP stock assessment of the eastern Atlantic and Mediterranean bluefin tuna

Author

Carrano, C., Maguire, J.-j., Kerr, L., Walter, J., Lauretta, M., Rouyer, Tristan, Cadrin, S.x., Carrano, C., Maguire, J.-j., Kerr, L., Walter, J., Lauretta, M., Rouyer, Tristan, and Cadrin, S.x.

Abstract

The Age Structured Assessment Program (ASAP) was applied to Eastern Atlantic and Mediterranean Atlantic Bluefin tuna for the 2022 stock assessment. Previous single-fleet applications of ASAP for the 2017 and 2020 Atlantic Bluefin tuna assessments were updated and revised, and alternative models with fleet structure were explored. The single-fleet ASAP runs generally fit the data well, and were retrospectively consistent, but residual patterns in age composition and uncertainty in selectivity parameters could not be resolved. Model estimates suggest a substantial change in selectivity in the late 1990s. Multi-fleet ASAP models were developed to fit catch data and estimate selectivity for each index fleet and the Mediterranean purse seine fleet. Multi-fleet-based runs were also retrospectively consistent and fit the available data well, with some residual patterns, but catch data by fleet need revision. Status determination from single-fleet and provisional multi-fleet runs was similar: The stock recovered over the last decade from strong recruitment and low fishing mortality, the estimate of 2020 fishing mortality was much less than F0.1, and the estimate of 2020 spawning biomass was much greater than SSBF0.1., Le programme d’évaluation structuré par âge (ASAP) a été appliqué au thon rouge de l’Atlantique Est et de la Méditerranée pour l’évaluation du stock de 2022. Les applications précédentes d’ASAP à flottille unique pour les évaluations du thon rouge de l’Atlantique de 2017 et 2020 ont été mises à jour et révisées et des modèles alternatifs avec une structure de la flottille ont été étudiés. Les scénarios de ASAP à flottille unique s'ajustent généralement bien aux données et sont rétrospectivement cohérents, mais les schémas résiduels de la composition par âge et l'incertitude des paramètres de sélectivité n'ont pas pu être résolus. Les estimations du modèle suggèrent un changement substantiel de la sélectivité à la fin des années 1990. Des modèles ASAP pluri-flottilles ont été développés pour ajuster les données de captures et estimer la sélectivité de chaque flottille des indices et pour la flottille des senneurs de la Méditerranée. Les scénarios pluri-flottilles étaient également rétrospectivement cohérents et s’ajustaient bien aux données disponibles avec certains schémas résiduels, mais les données de capture par flottille ont dû être révisées. La détermination de l'état à partir des scénarios à flottille unique et à flottilles multiples provisoires était similaire, à savoir : le stock s'est rétabli au cours de la dernière décennie grâce à un fort recrutement et à une faible mortalité par pêche, l'estimation de la mortalité par pêche en 2020 était bien inférieure à F0,1 et l'estimation de la biomasse reproductrice en 2020 était bien supérieure à SSBF0,1., Se aplicó el Programa de evaluación estructurada por edad (ASAP) al atún rojo del Atlántico este y Mediterráneo para la evaluación de stock de 2022. Se actualizaron y revisaron las aplicaciones previas de ASAP de una sola flota para las evaluaciones de atún rojo del Atlántico de 2017 y 2020, y se exploraron modelos alternativos con una estructura de la flota. En general, los ensayos de ASAP de una sola flota se ajustaron bien a los datos y fueron coherentes desde el punto de vista retrospectivo, pero no se pudieron resolver los patrones residuales en la composición por edad y la incertidumbre en los parámetros de selectividad. Las estimaciones del modelo sugieren un cambio importante en la selectividad a finales de la década de 1990. Se desarrollaron modelos ASAP multiflota para ajustar los datos de captura y estimar la selectividad para cada flota del índice y la flota de cerco del Mediterráneo. Los ensayos basados en múltiples flotas también fueron coherentes desde el punto de vista retrospectivo y se ajustaron bien a los datos disponibles, con algunos patrones residuales, pero los datos de captura por flota necesitan ser revisados. La determinación del estado a partir de ensayos de una sola flota y de múltiples flotas provisiones fueron similares: El stock se recuperó durante la última década gracias a un fuerte reclutamiento y a una baja mortalidad por pesca, la estimación de la mortalidad por pesca de 2020 fue mucho inferior a F0.1 y la estimación de la biomasa reproductora de 2020 fue mucho superior a SSBF0.1.

Published
2022

33. L’âge cérébral radiomique prédit le pronostic fonctionnel après un avc ischémique.

Author

Bretzner, M, Bonkhoff, A, Schirmer, M, Hong, S, Dalca, A, Donahue, K, Giese, A-K, Etherton, M, Rist, P, Nardin, M, Regenhardt, R, Leclerc, X, Lopes, R, Gautherot, M, Wang, C, Benavente, O, Cole, J, Donatti, A, Griessenauer, C, Heitsch, L, Holmegaard, L, Jood, K, Conde, JJ, Kittner, S, Lemmens, R, Levi, C, McArdle, P, McDonough, C, Meshia, J, Phuah, C-L, Rolfs, A, Ropele, S, Rosand, J, Roquer, J, Rundek, T, Sacco, R, Schmidt, R, Sharma, P, Slowik, A, Sousa, A, Stanne, T, Strbian, D, Tatlisumak, T, Thijs, V, Vagala, A, Wasselius, J, Woo, D, Wu, O, Zand, R, Worrall, B, Maguire, J, Lindgren, A, Jern, C, Golland, P, Kuchcinski, G, Rost, N, Bretzner, M, Bonkhoff, A, Schirmer, M, Hong, S, Dalca, A, Donahue, K, Giese, A-K, Etherton, M, Rist, P, Nardin, M, Regenhardt, R, Leclerc, X, Lopes, R, Gautherot, M, Wang, C, Benavente, O, Cole, J, Donatti, A, Griessenauer, C, Heitsch, L, Holmegaard, L, Jood, K, Conde, JJ, Kittner, S, Lemmens, R, Levi, C, McArdle, P, McDonough, C, Meshia, J, Phuah, C-L, Rolfs, A, Ropele, S, Rosand, J, Roquer, J, Rundek, T, Sacco, R, Schmidt, R, Sharma, P, Slowik, A, Sousa, A, Stanne, T, Strbian, D, Tatlisumak, T, Thijs, V, Vagala, A, Wasselius, J, Woo, D, Wu, O, Zand, R, Worrall, B, Maguire, J, Lindgren, A, Jern, C, Golland, P, Kuchcinski, G, and Rost, N

Published
2022

35. Handheld Devices: The Barrier for Parents with Mental Health Difficulties in Child Outcomes

Author

Bui, NH, Cruickshank, M, McAloon, J, Maguire, J, Bui, NH, Cruickshank, M, McAloon, J, and Maguire, J

Abstract

The parenting landscape has changed dramatically over the last decade with the increasing prevalence of screen time. There is a growing body of evidence that handheld devices may disrupt fundamental parent-child interactions, however little is known regarding the effect of these devices for parents with mental health difficulties on child outcomes. The Australian Department of Health (2019) has recommended that children between two and five years old should be limited to less than an hour of screen time per day. A cross-sectional study of 214 parents with children aged 4.5–6 years old was conducted to examine the relationship between parental mental health, handheld screen time and child outcomes. Results from bivariate correlations indicated parental anxiety, depression and stress was significantly associated with parental phone use, such that greater symptoms was associated with increased screen time. Parental anxiety was also associated with parental tablet use, and child phone and tablet use. Further analyses showed that no mediation effects were observed among key variables. Most children were adhering to screen time guidelines, which implied that children showed reduced internalising and externalising problems. These findings have implications for policymakers and allied health professionals to consider the effects of parental mental health within the screen time framework for children’s wellbeing.

Published
2022

36. The association between fatigue severity and risk of falls among middle-aged and older Australian stroke survivors.

Author

Sibbritt, D, Bayes, J, Peng, W, Maguire, J, Ladanyi, S, Adams, J, Sibbritt, D, Bayes, J, Peng, W, Maguire, J, Ladanyi, S, and Adams, J

Abstract

BACKGROUND: Fatigue is a common and often debilitating symptom experienced by many stroke survivors. Significant post stroke fatigue may predispose individuals to other health complications, such as falls, which can lead to fractures and soft tissue injuries. Only limited research has examined the association between fatigue and falls in stroke survivors. METHODS: Data were obtained from the Sax Institute's 45 and Up Study, from a subset of individuals who had experienced a stroke. The Modified Fatigue Impact Scale-5-item version (MFIS-5) was used to measure the level of fatigue. A logistic regression model, adjusted for stroke characteristics and comorbidities, was used to determine the magnitude of association between change in fatigue score and odds of having had a fall. RESULTS: A total of 576 participants completed the questionnaire. A total of 214 (37.2%) participants reported having had a fall in the previous 12 months. There was a statistically significant association between fatigue scores and fall status (p < 0.001). Specifically, for every 1-point increase in the fatigue score (MFIS-5) (i.e. higher level of fatigue), the odds of a person having a fall is 1.10 times greater (AOR = 1.10; 95% CI 1.05, 1.15; p < 0.001). CONCLUSION: This study revealed an association between an increasing risk of falls with increasing severity of post stroke fatigue. Accurate detection and management of fatigue may help reduce the risk of falls and should be the focus of future research.

Published
2022

37. Sustainable Wine. The discursive production of sustainability in the wine field

Author

Charters, S, Demossier, M, Dutton, J, Harding, G, Smith Maguire, J, Marks, D, Unwin, T, Navarini, G, Domaneschi, L, Charters, S, Demossier, M, Dutton, J, Harding, G, Smith Maguire, J, Marks, D, Unwin, T, Navarini, G, and Domaneschi, L

Abstract

This chapter addresses the question of sustainability, discussing some of the leading perspectives in wine studies about the theory and practice of sustainability. We start by illustrating how sustainability can be understood as a discursive field with a specific history and discontinuities, a set of conventional dominant definitions and a package of tools and devices to measure, evaluate and hence legitimate such classifications. Then we analyse what we have called ‘certification work’ in order to show how tools such as labels, reports, indicators and, mainly, certification schemes operate as discursive devices in the fields of wine worldwide. Finally, we point out the ambivalent effects of ‘certification work’ in the everyday process of winemaking and the respective practical management of such institutional contradictions. We conclude by critically discussing the ‘culture of sustainability’ in the field of wine and providing directions for a future research agenda.

Published
2022

38. Are clinicians using routinely collected data to drive practice improvement? A cross-sectional survey

Author

Gawthorne, J, Fasugba, O, Levi, C, Mcinnes, E, Ferguson, C, Mcneil, J, Cadilhac, DA, Everett, B, Fernandez, R, Fry, M, Goldsmith, H, Hickman, L, Jackson, D, Maguire, J, Murray, E, Perry, L, Middleton, S, Gawthorne, J, Fasugba, O, Levi, C, Mcinnes, E, Ferguson, C, Mcneil, J, Cadilhac, DA, Everett, B, Fernandez, R, Fry, M, Goldsmith, H, Hickman, L, Jackson, D, Maguire, J, Murray, E, Perry, L, and Middleton, S

Published
2022

47. Are Clinicians Using Routinely Collected Data to Drive Practice Improvement? A Cross Sectional Survey

Author

Gawthorne, J, Fasugba, O, Levi, C, McInnes, E, Ferguson, C, McNeil, J, Cadilhac, DA, Everett, B, Fernandez, R, Fry, M, Goldsmith, H, Hickman, L, Jackson, D, Maguire, J, Murray, E, Perry, L, and Middleton, S

Subjects
11 Medical and Health Sciences, 17 Psychology and Cognitive Sciences, Health Policy & Services
Abstract

BackgroundClinical registry participation is a measure of healthcare quality. Limited knowledge exists on Australian hospitals participation in clinical registries and whether this registry data informs quality improvement initiatives. Hence, our study aimed to; identify participation in clinical registries; determine if registry data inform quality improvement initiatives; identify registry participation enablers; and clinicians' educational needs to improve use of registry data to drive practice change.Methods: A self-administered survey was distributed to staff coordinating registries in seven hospitals in New South Wales, Australia. Eligible registries were international, national and state-based clinical, condition/disease-specific and device/product registries.Results: Response rate was 70% (97/139). Sixty-two (64%) respondents contributed data to 46 eligible registries. Registry reports were most often received by nurses (61%) and infrequently by hospital executives (8.4%). Less than half used registry data 'always' or 'often' to influence practice improvement (48%) and care pathways (49%). Protected time for data collection (87%) and benchmarking (79%) were 'very likely' or 'likely' to promote continued participation. Over half 'strongly agreed' or 'agreed' that clinical practice improvement training (79%) and evidence-practice gap identification (77%) would optimise use of registry data.Conclusions: Registry data are generally only visible to local speciality units and not routinely used to inform quality improvement. Centralised on-going registry funding, accessible and transparent integrated information systems, combined with data informed improvement science education could be first steps to promote quality data-driven clinical improvement initiatives.

Published
2021

48. THE CONCISE GUIDE TO PHARMACOLOGY 2015/16: Overview

Author

Alexander, Stephen PH, Kelly, Eamonn, Marrion, Neil, Peters, John A, Benson, Helen E, Faccenda, Elena, Pawson, Adam J, Sharman, Joanna L, Southan, Christopher, Buneman, Peter O, Catterall, William A, Cidlowski, John A, Davenport, Anthony P, Fabbro, Doriano, Fan, Grace, McGrath, John C, Spedding, Michael, Davies, Jamie A, Aldrich, R, Attali, B, Bäck, M l, Barnes, N M, Bathgate, R, Beart, P M, Becirovic, E, Biel, M, Birdsall, N J, Boison, D, Bräuner-Osborne, H, Bröer, S, Bryant, C, Burnstock, G, Burris, T, Cain, D, Calo, G, Chan, S L, Chandy, K G, Chiang, N, Christakos, S, Christopoulos, A, Chun, J J, Chung, J-J, Clapham, D E, Connor, M A, Coons, L, Cox, H M, Dautzenberg, F M, Dent, G, Douglas, S D, Dubocovich, M L, Edwards, D P, Farndale, R, Fong, T M, Forrest, D, Fowler, C J, Fuller, P, Gainetdinov, R R, Gershengorn, M A, Goldin, A, Goldstein, S AN, Grimm, S L, Grissmer, S, Gundlach, A L, Hagenbuch, B, Hammond, J R, Hancox, J C, Hartig, S, Hauger, R L, Hay, D L, Hébert, T, Hollenberg, A N, Holliday, N D, Hoyer, D, Ijzerman, A P, Inui, K I, Ishii, S, Jacobson, K A, Jan, L Y, Jarvis, G E, Jensen, R, Jetten, A, Jockers, R, Kaczmarek, L K, Kanai, Y, Kang, H S, Karnik, S, Kerr, I D, Korach, K S, Lange, C A, Larhammar, D, Leeb-Lundberg, F, Leurs, R, Lolait, S J, Macewan, D, Maguire, J J, May, J M, Mazella, J, Mcardle, C A, Mcdonnell, D P, Michel, M C, Miller, L J, Mitolo, V, Monie, T, Monk, P N, Mouillac, B, Murphy, P M, Nahon, J-L, Nerbonne, J, Nichols, C G, Norel, X, Oakley, R, Offermanns, S, Palmer, L G, Panaro, M A, Perez-Reyes, E, Pertwee, R G, Pike, J W, Pin, J P, Pintor, S, Plant, L D, Poyner, D R, Prossnitz, E R, Pyne, S, Ren, D, Richer, J K, Rondard, P, Ross, R A, Sackin, H, Safi, R, Sanguinetti, M C, Sartorius, C A, Segaloff, D L, Sladek, F M, Stewart, G, Stoddart, L A, Striessnig, J, Summers, R J, Takeda, Y, Tetel, M, Toll, L, Trimmer, J S, Tsai, M-J, Tsai, S Y, Tucker, S, Usdin, T B, Vilargada, J-P, Vore, M, Ward, D T, Waxman, S G, Webb, P, Wei, A D, Weigel, N, Willars, G B, Winrow, C, Wong, S S, Wulff, H, Ye, R D, Young, M, and Zajac, J-M

Published
2015
Full Text
View/download PDF

49. Heritability of young- and old-onset ischaemic stroke

Author

Bluher, A., Devan, W. J., Holliday, E. G., Nalls, M., Parolo, S., Bione, S., Giese, A.-K., Boncoraglio, G. B., Maguire, J. M., Müller-Nurasyid, M., Gieger, C., Meschia, J. F., Rosand, J., Rolfs, A., Kittner, S. J., Mitchell, B. D., OʼConnell, J. R., and Cheng, Y.-C.

Published
2015
Full Text
View/download PDF

50. A Field Experiment of Minimum Physical Fitness of Children with Visual Impairments.

Author

Meek, G. A. and Maguire, J. F.

Abstract

This experiment employed simple exercises to ascertain whether 49 children (ages 9-16) with partial or complete blindness had lesser levels of physical fitness than 24 fully sighted controls. Results found low rates of fitness among both groups, but considerably lower among students with visual impairments. Possible problems with test validity are discussed. (PB)

Published
1996

Catalog

Books, media, physical & digital resources
See catalog results