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3. Hijacking of N-fixing legume albumin-1 genes enables the cyclization and stabilization of defense peptides

Author

Edward K. Gilding, Mark A. Jackson, Linh T. T. Nguyen, Brett R. Hamilton, Katherine A. Farquharson, Wing L. Ho, Kuok Yap, Carolyn J. Hogg, Katherine Belov, and David J. Craik

Subjects
Science
Abstract

Abstract The legume albumin-1 gene family, arising after nodulation, encodes linear a- and b-chain peptides for nutrient storage and defense. Intriguingly, in one prominent legume, Clitoria ternatea, the b-chains are replaced by domains producing ultra-stable cyclic peptides called cyclotides. The mechanism of this gene hijacking is until now unknown. Cyclotides require recruitment of ligase-type asparaginyl endopeptidases (AEPs) for maturation (cyclization), necessitating co-evolution of two gene families. Here we compare a chromosome-level C. ternatea genome with grain legumes to reveal an 8 to 40-fold expansion of the albumin-1 gene family, enabling the additional loci to undergo diversification. Iterative rounds of albumin-1 duplication and diversification create four albumin-1 enriched genomic islands encoding cyclotides, where they are physically grouped by similar pI and net charge values. We identify an ancestral hydrolytic AEP that exhibits neofunctionalization and multiple duplication events to yield two ligase-type AEPs. We propose cyclotides arise by convergence in C. ternatea where their presence enhances defense from biotic attack, thus increasing fitness compared to lineages with linear b-chains and ultimately driving the replacement of b-chains with cyclotides.

Published
2024
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5. Blood pressure-lowering treatment for prevention of major cardiovascular diseases in people with and without type 2 diabetes: an individual participant-level data meta-analysis

Author

Agodoa, L, Algra, A, Asselbergs, F W, Beckett, N, Berge, E, Black, H, Brouwers, F P J, Brown, M, Bulpitt, C J, Byington, B, Cutler, J, Devereaux, R B, Dwyer, J, Estacio, R, Fagard, R, Fox, K, Fukui, T, Imai, Y, Ishii, M, Julius, S, Kanno, Y, Kjeldsen, S E, Kostis, J, Kuramoto, K, Lanke, J, Lewis, E, Lewis, J, Lievre, M, Lindholm, L H, Lueders, S, MacMahon, S, Mancia, G, Matsuzaki, M, Mehlum, M H, Nissen, S, Ogawa, H, Ogihara, T, Ohkubo, T, Palmer, C, Patel, A, Pfeffer, M, Poulter, N R, Rakugi, H, Reboldi, G, Reid, C, Remuzzi, G, Ruggenenti, P, Saruta, T, Schrader, J, Schrier, R, Sever, P, Sleight, P, Staessen, J A, Suzuki, H, Thijs, L, Ueshima, K, Umemoto, S, van Gilst, W H, Verdecchia, P, Wachtell, K, Whelton, P, Wing, L, Yui, Y, Yusuf, S, Zanchetti, A, Zhang, Z Y, Anderson, C, Baigent, C, Brenner, BM, Collins, R, de Zeeuw, D, Lubsen, J, Malacco, E, Neal, B, Perkovic, V, Pitt, B, Rodgers, A, Rothwell, P, Salimi-Khorshidi, G, Sundström, J, Turnbull, F, Viberti, G, Wang, J, Nazarzadeh, Milad, Bidel, Zeinab, Canoy, Dexter, Copland, Emma, Bennett, Derrick A, Dehghan, Abbas, Davey Smith, George, Holman, Rury R, Woodward, Mark, Gupta, Ajay, Adler, Amanda I, Wamil, Malgorzata, Sattar, Naveed, Cushman, William C, McManus, Richard J, Teo, Koon, Davis, Barry R, Chalmers, John, Pepine, Carl J, and Rahimi, Kazem

Published
2022
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6. Antihypertensive treatment and risk of cancer: an individual participant data meta-analysis

Author

Adler, A, Agodoa, L, Algra, A, Asselbergs, F W, Beckett, N, Berge, E, Black, H, Brouwers, F P J, Brown, M, Bulpitt, C J, Byington, B, Chalmers, J, Cushman, W C, Cutler, J, Davis, B R, Devereaux, R B, Dwyer, J, Estacio, R, Fagard, R, Fox, K, Fukui, T, Gupta, A K, Holman, R R, Imai, Y, Ishii, M, Julius, S, Kanno, Y, Kjeldsen, S E, Kostis, J, Kuramoto, K, Lanke, J, Lewis, E, Lewis, J, Lievre, M, Lindholm, L H, Lueders, S, MacMahon, S, Mancia, G, Matsuzaki, M, Mehlum, M H, Nissen, S, Ogawa, H, Ogihara, T, Ohkubo, T, Palmer, C, Patel, A, Pepine, C J, Pfeffer, M, Poulter, N R, Rakugi, H, Reboldi, G, Reid, C, Remuzzi, G, Ruggenenti, P, Saruta, T, Schrader, J, Schrier, R, Sever, P, Sleight, P, Staessen, J A, Suzuki, H, Thijs, L, Ueshima, K, Umemoto, S, van Gilst, W H, Verdecchia, P, Wachtell, K, Whelton, P, Wing, L, Woodward, M, Yui, Y, Yusuf, S, Zanchetti, A, Zhang, Z Y, Anderson, C, Baigent, C, Brenner, BM, Collins, R, de Zeeuw, D, Lubsen, J, Malacco, E, Neal, B, Perkovic, V, Pitt, B, Rodgers, A, Rothwell, P, Salimi-Khorshidi, G, Sundström, J, Turnbull, F, Viberti, G, Wang, J, Copland, Emma, Canoy, Dexter, Nazarzadeh, Milad, Bidel, Zeinab, Ramakrishnan, Rema, Woodward, Mark, Chalmers, John, Teo, Koon K, Pepine, Carl J, Davis, Barry R, Kjeldsen, Sverre, Sundström, Johan, and Rahimi, Kazem

Published
2021
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11. Multiple Sclerosis in the Asia Pacific Region: A Systematic Review of a Neglected Neurological Disease

Author

Wing L. Cheong, Devi Mohan, Narelle Warren, and Daniel D. Reidpath

Subjects
multiple sclerosis, epidemiology, Asia Pacific, prevalence, incidence, mortality, Neurology. Diseases of the nervous system, RC346-429
Abstract

Background: Multiple sclerosis is thought to be relatively uncommon in the Asia Pacific region with prevalence estimated between 0 and 20 per 100,000. There is reason to doubt these estimates due to the lack of data from many countries and the growing evidence of variability in prevalence across small geographic areas. This study was conducted to systematically review the population prevalence, incidence, mortality and disability progression estimates of MS within the Asia Pacific region.Methods: The systematic review was conducted on articles from 1985 till 31st July 2017 within the PubMed/MEDLINE, EMBASE, SCOPUS, and The Cochrane Library databases. The review included articles that were population-based studies conducted on patients with MS in the Asia Pacific region that reported either incidence, prevalence, mortality, or disease progression. Hospital-based studies and non-research articles were excluded to ensure that only information representative of the population was included for analysis. Data appraisal and extraction was done by independent reviewers. This review was registered with PROSPERO (ID: CRD42017082760).Findings: Of the 2,757 articles found, 16 studies were included. Information on 6 (18.75%) of 32 Asia Pacific countries was found, with data representing 8% of the total population. Prevalence estimates were available for 6 countries while estimates for incidence (3 countries), mortality (4 countries), and disease progression (2 countries) were limited.Interpretation: The lack of epidemiological data available in the Asia Pacific region creates a blind spot in the surveillance of MS which obscures the true burden of MS, causing patients to struggle to receive the resources and funding that they need.

Published
2018
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12. Blood pressure-lowering treatment for prevention of major cardiovascular diseases in people with and without type 2 diabetes: an individual participant-level data meta-analysis

Author

Nazarzadeh, Milad, primary, Bidel, Zeinab, additional, Canoy, Dexter, additional, Copland, Emma, additional, Bennett, Derrick A, additional, Dehghan, Abbas, additional, Davey Smith, George, additional, Holman, Rury R, additional, Woodward, Mark, additional, Gupta, Ajay, additional, Adler, Amanda I, additional, Wamil, Malgorzata, additional, Sattar, Naveed, additional, Cushman, William C, additional, McManus, Richard J, additional, Teo, Koon, additional, Davis, Barry R, additional, Chalmers, John, additional, Pepine, Carl J, additional, Rahimi, Kazem, additional, Agodoa, L, additional, Algra, A, additional, Asselbergs, F W, additional, Beckett, N, additional, Berge, E, additional, Black, H, additional, Brouwers, F P J, additional, Brown, M, additional, Bulpitt, C J, additional, Byington, B, additional, Cutler, J, additional, Devereaux, R B, additional, Dwyer, J, additional, Estacio, R, additional, Fagard, R, additional, Fox, K, additional, Fukui, T, additional, Imai, Y, additional, Ishii, M, additional, Julius, S, additional, Kanno, Y, additional, Kjeldsen, S E, additional, Kostis, J, additional, Kuramoto, K, additional, Lanke, J, additional, Lewis, E, additional, Lewis, J, additional, Lievre, M, additional, Lindholm, L H, additional, Lueders, S, additional, MacMahon, S, additional, Mancia, G, additional, Matsuzaki, M, additional, Mehlum, M H, additional, Nissen, S, additional, Ogawa, H, additional, Ogihara, T, additional, Ohkubo, T, additional, Palmer, C, additional, Patel, A, additional, Pfeffer, M, additional, Poulter, N R, additional, Rakugi, H, additional, Reboldi, G, additional, Reid, C, additional, Remuzzi, G, additional, Ruggenenti, P, additional, Saruta, T, additional, Schrader, J, additional, Schrier, R, additional, Sever, P, additional, Sleight, P, additional, Staessen, J A, additional, Suzuki, H, additional, Thijs, L, additional, Ueshima, K, additional, Umemoto, S, additional, van Gilst, W H, additional, Verdecchia, P, additional, Wachtell, K, additional, Whelton, P, additional, Wing, L, additional, Yui, Y, additional, Yusuf, S, additional, Zanchetti, A, additional, Zhang, Z Y, additional, Anderson, C, additional, Baigent, C, additional, Brenner, BM, additional, Collins, R, additional, de Zeeuw, D, additional, Lubsen, J, additional, Malacco, E, additional, Neal, B, additional, Perkovic, V, additional, Pitt, B, additional, Rodgers, A, additional, Rothwell, P, additional, Salimi-Khorshidi, G, additional, Sundström, J, additional, Turnbull, F, additional, Viberti, G, additional, and Wang, J, additional

Published
2022
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14. Age-stratified and blood-pressure-stratified effects of blood-pressure-lowering pharmacotherapy for the prevention of cardiovascular disease and death: an individual participant-level data meta-analysis

Author

Rahimi, K, Bidel, Z, Nazarzadeh, M, Copland, E, Canoy, D, Wamil, M, Majert, J, Mcmanus, R, Adler, A, Agodoa, L, Algra, A, Asselbergs, F, Beckett, N, Berge, E, Black, H, Boersma, E, Brouwers, F, Brown, M, Brugts, J, Bulpitt, C, Byington, R, Cushman, W, Cutler, J, Devereaux, R, Dwyer, J, Estacio, R, Fagard, R, Fox, K, Fukui, T, Gupta, A, Holman, R, Imai, Y, Ishii, M, Julius, S, Kanno, Y, Kjeldsen, S, Kostis, J, Kuramoto, K, Lanke, J, Lewis, E, Lewis, J, Lievre, M, Lindholm, L, Lueders, S, Macmahon, S, Mancia, G, Matsuzaki, M, Mehlum, M, Nissen, S, Ogawa, H, Ogihara, T, Ohkubo, T, Palmer, C, Patel, A, Pfeffer, M, Pitt, B, Poulter, N, Rakugi, H, Reboldi, G, Reid, C, Remuzzi, G, Ruggenenti, P, Saruta, T, Schrader, J, Schrier, R, Sever, P, Sleight, P, Staessen, J, Suzuki, H, Thijs, L, Ueshima, K, Umemoto, S, van Gilst, W, Verdecchia, P, Wachtell, K, Whelton, P, Wing, L, Woodward, M, Yui, Y, Yusuf, S, Zanchetti, A, Zhang, Z, Anderson, C, Baigent, C, Brenner, B, Collins, R, de Zeeuw, D, Lubsen, J, Malacco, E, Neal, B, Perkovic, V, Rodgers, A, Rothwell, P, Salimi-Khorshidi, G, Sundstrom, J, Turnbull, F, Viberti, G, Wang, J, Chalmers, J, Davis, B, Pepine, C, Teo, K, Rahimi K., Bidel Z., Nazarzadeh M., Copland E., Canoy D., Wamil M., Majert J., McManus R., Adler A., Agodoa L., Algra A., Asselbergs F. W., Beckett N. S., Berge E., Black H., Boersma E., Brouwers F. P. J., Brown M., Brugts J. J., Bulpitt C. J., Byington R. P., Cushman W. C., Cutler J., Devereaux R. B., Dwyer J. P., Estacio R., Fagard R., Fox K., Fukui T., Gupta A. K., Holman R. R., Imai Y., Ishii M., Julius S., Kanno Y., Kjeldsen S. E., Kostis J., Kuramoto K., Lanke J., Lewis E., Lewis J. B., Lievre M., Lindholm L. H., Lueders S., MacMahon S., Mancia G., Matsuzaki M., Mehlum M. H., Nissen S., Ogawa H., Ogihara T., Ohkubo T., Palmer C. R., Patel A., Pfeffer M. A., Pitt B., Poulter N. R., Rakugi H., Reboldi G., Reid C., Remuzzi G., Ruggenenti P., Saruta T., Schrader J., Schrier R., Sever P., Sleight P., Staessen J. A., Suzuki H., Thijs L., Ueshima K., Umemoto S., van Gilst W. H., Verdecchia P., Wachtell K., Whelton P., Wing L., Woodward M., Yui Y., Yusuf S., Zanchetti A., Zhang Z. -Y., Anderson C., Baigent C., Brenner B. M., Collins R., de Zeeuw D., Lubsen J., Malacco E., Neal B., Perkovic V., Rodgers A., Rothwell P., Salimi-Khorshidi G., Sundstrom J., Turnbull F., Viberti G., Wang J., Chalmers J., Davis B. R., Pepine C. J., Teo K. K., Rahimi, K, Bidel, Z, Nazarzadeh, M, Copland, E, Canoy, D, Wamil, M, Majert, J, Mcmanus, R, Adler, A, Agodoa, L, Algra, A, Asselbergs, F, Beckett, N, Berge, E, Black, H, Boersma, E, Brouwers, F, Brown, M, Brugts, J, Bulpitt, C, Byington, R, Cushman, W, Cutler, J, Devereaux, R, Dwyer, J, Estacio, R, Fagard, R, Fox, K, Fukui, T, Gupta, A, Holman, R, Imai, Y, Ishii, M, Julius, S, Kanno, Y, Kjeldsen, S, Kostis, J, Kuramoto, K, Lanke, J, Lewis, E, Lewis, J, Lievre, M, Lindholm, L, Lueders, S, Macmahon, S, Mancia, G, Matsuzaki, M, Mehlum, M, Nissen, S, Ogawa, H, Ogihara, T, Ohkubo, T, Palmer, C, Patel, A, Pfeffer, M, Pitt, B, Poulter, N, Rakugi, H, Reboldi, G, Reid, C, Remuzzi, G, Ruggenenti, P, Saruta, T, Schrader, J, Schrier, R, Sever, P, Sleight, P, Staessen, J, Suzuki, H, Thijs, L, Ueshima, K, Umemoto, S, van Gilst, W, Verdecchia, P, Wachtell, K, Whelton, P, Wing, L, Woodward, M, Yui, Y, Yusuf, S, Zanchetti, A, Zhang, Z, Anderson, C, Baigent, C, Brenner, B, Collins, R, de Zeeuw, D, Lubsen, J, Malacco, E, Neal, B, Perkovic, V, Rodgers, A, Rothwell, P, Salimi-Khorshidi, G, Sundstrom, J, Turnbull, F, Viberti, G, Wang, J, Chalmers, J, Davis, B, Pepine, C, Teo, K, Rahimi K., Bidel Z., Nazarzadeh M., Copland E., Canoy D., Wamil M., Majert J., McManus R., Adler A., Agodoa L., Algra A., Asselbergs F. W., Beckett N. S., Berge E., Black H., Boersma E., Brouwers F. P. J., Brown M., Brugts J. J., Bulpitt C. J., Byington R. P., Cushman W. C., Cutler J., Devereaux R. B., Dwyer J. P., Estacio R., Fagard R., Fox K., Fukui T., Gupta A. K., Holman R. R., Imai Y., Ishii M., Julius S., Kanno Y., Kjeldsen S. E., Kostis J., Kuramoto K., Lanke J., Lewis E., Lewis J. B., Lievre M., Lindholm L. H., Lueders S., MacMahon S., Mancia G., Matsuzaki M., Mehlum M. H., Nissen S., Ogawa H., Ogihara T., Ohkubo T., Palmer C. R., Patel A., Pfeffer M. A., Pitt B., Poulter N. R., Rakugi H., Reboldi G., Reid C., Remuzzi G., Ruggenenti P., Saruta T., Schrader J., Schrier R., Sever P., Sleight P., Staessen J. A., Suzuki H., Thijs L., Ueshima K., Umemoto S., van Gilst W. H., Verdecchia P., Wachtell K., Whelton P., Wing L., Woodward M., Yui Y., Yusuf S., Zanchetti A., Zhang Z. -Y., Anderson C., Baigent C., Brenner B. M., Collins R., de Zeeuw D., Lubsen J., Malacco E., Neal B., Perkovic V., Rodgers A., Rothwell P., Salimi-Khorshidi G., Sundstrom J., Turnbull F., Viberti G., Wang J., Chalmers J., Davis B. R., Pepine C. J., and Teo K. K.

Abstract

Background: The effects of pharmacological blood-pressure-lowering on cardiovascular outcomes in individuals aged 70 years and older, particularly when blood pressure is not substantially increased, is uncertain. We compared the effects of blood-pressure-lowering treatment on the risk of major cardiovascular events in groups of patients stratified by age and blood pressure at baseline. Methods: We did a meta-analysis using individual participant-level data from randomised controlled trials of pharmacological blood-pressure-lowering versus placebo or other classes of blood-pressure-lowering medications, or between more versus less intensive treatment strategies, which had at least 1000 persons-years of follow-up in each treatment group. Participants with previous history of heart failure were excluded. Data were obtained from the Blood Pressure Lowering Treatment Triallists' Collaboration. We pooled the data and categorised participants into baseline age groups (<55 years, 55–64 years, 65–74 years, 75–84 years, and ≥85 years) and blood pressure categories (in 10 mm Hg increments from <120 mm Hg to ≥170 mm Hg systolic blood pressure and from <70 mm Hg to ≥110 mm Hg diastolic). We used a fixed effects one-stage approach and applied Cox proportional hazard models, stratified by trial, to analyse the data. The primary outcome was defined as either a composite of fatal or non-fatal stroke, fatal or non-fatal myocardial infarction or ischaemic heart disease, or heart failure causing death or requiring hospital admission. Findings: We included data from 358 707 participants from 51 randomised clinical trials. The age of participants at randomisation ranged from 21 years to 105 years (median 65 years [IQR 59–75]), with 42 960 (12·0%) participants younger than 55 years, 128 437 (35·8%) aged 55–64 years, 128 506 (35·8%) 65–74 years, 54 016 (15·1%) 75–84 years, and 4788 (1·3%) 85 years and older. The hazard ratios for the risk of major cardiovascular events per 5 mm Hg

Published
2021

15. Pharmacological blood pressure lowering for primary and secondary prevention of cardiovascular disease across different levels of blood pressure: an individual participant-level data meta-analysis

Author

Adler, A, Agodoa, L, Algra, A, Asselbergs, F, Beckett, N, Berge, E, Black, H, Brouwers, F, Brown, M, Bulpitt, C, Byington, R, Chalmers, J, Cushman, W, Cutler, J, Davis, B, Devereaux, R, Dwyer, J, Estacio, R, Fagard, R, Fox, K, Fukui, T, Gupta, A, Holman, R, Imai, Y, Ishii, M, Julius, S, Kanno, Y, Kjeldsen, S, Kostis, J, Kuramoto, K, Lanke, J, Lewis, E, Lewis, J, Lievre, M, Lindholm, L, Lueders, S, Macmahon, S, Mancia, G, Matsuzaki, M, Mehlum, M, Nissen, S, Ogawa, H, Ogihara, T, Ohkubo, T, Palmer, C, Patel, A, Pepine, C, Pfeffer, M, Pitt, B, Poulter, N, Rakugi, H, Reboldi, G, Reid, C, Remuzzi, G, Ruggenenti, P, Saruta, T, Schrader, J, Schrier, R, Sever, P, Sleight, P, Staessen, J, Suzuki, H, Thijs, L, Ueshima, K, Umemoto, S, van Gilst, W, Verdecchia, P, Wachtell, K, Whelton, P, Wing, L, Woodward, M, Yui, Y, Yusuf, S, Zanchetti, A, Zhang, Z, Anderson, C, Baigent, C, Brenner, B, Collins, R, de Zeeuw, D, Lubsen, J, Malacco, E, Neal, B, Perkovic, V, Rodgers, A, Rothwell, P, Salimi-Khorshidi, G, Sundstrom, J, Turnbull, F, Viberti, G, Wang, J, Adler A., Agodoa L., Algra A., Asselbergs F. W., Beckett N. S., Berge E., Black H., Brouwers F. P. J., Brown M., Bulpitt C. J., Byington R. P., Chalmers J., Cushman W. C., Cutler J., Davis B. R., Devereaux R. B., Dwyer J., Estacio R., Fagard R., Fox K., Fukui T., Gupta A. K., Holman R. R., Imai Y., Ishii M., Julius S., Kanno Y., Kjeldsen S. E., Kostis J., Kuramoto K., Lanke J., Lewis E., Lewis J. B., Lievre M., Lindholm L. H., Lueders S., MacMahon S., Mancia G., Matsuzaki M., Mehlum M. H., Nissen S., Ogawa H., Ogihara T., Ohkubo T., Palmer C. R., Patel A., Pepine C. J., Pfeffer M. A., Pitt B., Poulter N. R., Rakugi H., Reboldi G., Reid C., Remuzzi G., Ruggenenti P., Saruta T., Schrader J., Schrier R., Sever P., Sleight P., Staessen J. A., Suzuki H., Thijs L., Ueshima K., Umemoto S., van Gilst W. H., Verdecchia P., Wachtell K., Whelton P., Wing L., Woodward M., Yui Y., Yusuf S., Zanchetti A., Zhang Z. -Y., Anderson C., Baigent C., Brenner B. M., Collins R., de Zeeuw D., Lubsen J., Malacco E., Neal B., Perkovic V., Rodgers A., Rothwell P., Salimi-Khorshidi G., Sundstrom J., Turnbull F., Viberti G., Wang J., Adler, A, Agodoa, L, Algra, A, Asselbergs, F, Beckett, N, Berge, E, Black, H, Brouwers, F, Brown, M, Bulpitt, C, Byington, R, Chalmers, J, Cushman, W, Cutler, J, Davis, B, Devereaux, R, Dwyer, J, Estacio, R, Fagard, R, Fox, K, Fukui, T, Gupta, A, Holman, R, Imai, Y, Ishii, M, Julius, S, Kanno, Y, Kjeldsen, S, Kostis, J, Kuramoto, K, Lanke, J, Lewis, E, Lewis, J, Lievre, M, Lindholm, L, Lueders, S, Macmahon, S, Mancia, G, Matsuzaki, M, Mehlum, M, Nissen, S, Ogawa, H, Ogihara, T, Ohkubo, T, Palmer, C, Patel, A, Pepine, C, Pfeffer, M, Pitt, B, Poulter, N, Rakugi, H, Reboldi, G, Reid, C, Remuzzi, G, Ruggenenti, P, Saruta, T, Schrader, J, Schrier, R, Sever, P, Sleight, P, Staessen, J, Suzuki, H, Thijs, L, Ueshima, K, Umemoto, S, van Gilst, W, Verdecchia, P, Wachtell, K, Whelton, P, Wing, L, Woodward, M, Yui, Y, Yusuf, S, Zanchetti, A, Zhang, Z, Anderson, C, Baigent, C, Brenner, B, Collins, R, de Zeeuw, D, Lubsen, J, Malacco, E, Neal, B, Perkovic, V, Rodgers, A, Rothwell, P, Salimi-Khorshidi, G, Sundstrom, J, Turnbull, F, Viberti, G, Wang, J, Adler A., Agodoa L., Algra A., Asselbergs F. W., Beckett N. S., Berge E., Black H., Brouwers F. P. J., Brown M., Bulpitt C. J., Byington R. P., Chalmers J., Cushman W. C., Cutler J., Davis B. R., Devereaux R. B., Dwyer J., Estacio R., Fagard R., Fox K., Fukui T., Gupta A. K., Holman R. R., Imai Y., Ishii M., Julius S., Kanno Y., Kjeldsen S. E., Kostis J., Kuramoto K., Lanke J., Lewis E., Lewis J. B., Lievre M., Lindholm L. H., Lueders S., MacMahon S., Mancia G., Matsuzaki M., Mehlum M. H., Nissen S., Ogawa H., Ogihara T., Ohkubo T., Palmer C. R., Patel A., Pepine C. J., Pfeffer M. A., Pitt B., Poulter N. R., Rakugi H., Reboldi G., Reid C., Remuzzi G., Ruggenenti P., Saruta T., Schrader J., Schrier R., Sever P., Sleight P., Staessen J. A., Suzuki H., Thijs L., Ueshima K., Umemoto S., van Gilst W. H., Verdecchia P., Wachtell K., Whelton P., Wing L., Woodward M., Yui Y., Yusuf S., Zanchetti A., Zhang Z. -Y., Anderson C., Baigent C., Brenner B. M., Collins R., de Zeeuw D., Lubsen J., Malacco E., Neal B., Perkovic V., Rodgers A., Rothwell P., Salimi-Khorshidi G., Sundstrom J., Turnbull F., Viberti G., and Wang J.

Abstract

Background: The effects of pharmacological blood pressure lowering at normal or high-normal blood pressure ranges in people with or without pre-existing cardiovascular disease remains uncertain. We analysed individual participant data from randomised trials to investigate the effects of blood pressure lowering treatment on the risk of major cardiovascular events by baseline levels of systolic blood pressure. Methods: We did a meta-analysis of individual participant-level data from 48 randomised trials of pharmacological blood pressure lowering medications versus placebo or other classes of blood pressure-lowering medications, or between more versus less intensive treatment regimens, which had at least 1000 persons-years of follow-up in each group. Trials exclusively done with participants with heart failure or short-term interventions in participants with acute myocardial infarction or other acute settings were excluded. Data from 51 studies published between 1972 and 2013 were obtained by the Blood Pressure Lowering Treatment Trialists' Collaboration (Oxford University, Oxford, UK). We pooled the data to investigate the stratified effects of blood pressure-lowering treatment in participants with and without prevalent cardiovascular disease (ie, any reports of stroke, myocardial infarction, or ischaemic heart disease before randomisation), overall and across seven systolic blood pressure categories (ranging from <120 to ≥170 mm Hg). The primary outcome was a major cardiovascular event (defined as a composite of fatal and non-fatal stroke, fatal or non-fatal myocardial infarction or ischaemic heart disease, or heart failure causing death or requiring admission to hospital), analysed as per intention to treat. Findings: Data for 344 716 participants from 48 randomised clinical trials were available for this analysis. Pre-randomisation mean systolic/diastolic blood pressures were 146/84 mm Hg in participants with previous cardiovascular disease (n=157 728) and 157/8

Published
2021

25. Is Public Taste Improving?

Author

KLAR, WALTER H., TREMAINE, C. M., WINSLOW, LEON LOYAL, LAHEE, HENRY C., BARNES, EDWIN N. C., KIRBY, C. VALENTINE, MOSELY, ELEANOR, WING, L. B., WHITFORD, WILLIAM G., KARNAGHAN, ANNE WEBB, and FULLERTON, C. A.

Published
1930

27. Antihypertensive treatment and risk of cancer: an individual participant data meta-analysis

Author

Copland, Emma, primary, Canoy, Dexter, additional, Nazarzadeh, Milad, additional, Bidel, Zeinab, additional, Ramakrishnan, Rema, additional, Woodward, Mark, additional, Chalmers, John, additional, Teo, Koon K, additional, Pepine, Carl J, additional, Davis, Barry R, additional, Kjeldsen, Sverre, additional, Sundström, Johan, additional, Rahimi, Kazem, additional, Adler, A, additional, Agodoa, L, additional, Algra, A, additional, Asselbergs, F W, additional, Beckett, N, additional, Berge, E, additional, Black, H, additional, Brouwers, F P J, additional, Brown, M, additional, Bulpitt, C J, additional, Byington, B, additional, Chalmers, J, additional, Cushman, W C, additional, Cutler, J, additional, Davis, B R, additional, Devereaux, R B, additional, Dwyer, J, additional, Estacio, R, additional, Fagard, R, additional, Fox, K, additional, Fukui, T, additional, Gupta, A K, additional, Holman, R R, additional, Imai, Y, additional, Ishii, M, additional, Julius, S, additional, Kanno, Y, additional, Kjeldsen, S E, additional, Kostis, J, additional, Kuramoto, K, additional, Lanke, J, additional, Lewis, E, additional, Lewis, J, additional, Lievre, M, additional, Lindholm, L H, additional, Lueders, S, additional, MacMahon, S, additional, Mancia, G, additional, Matsuzaki, M, additional, Mehlum, M H, additional, Nissen, S, additional, Ogawa, H, additional, Ogihara, T, additional, Ohkubo, T, additional, Palmer, C, additional, Patel, A, additional, Pepine, C J, additional, Pfeffer, M, additional, Poulter, N R, additional, Rakugi, H, additional, Reboldi, G, additional, Reid, C, additional, Remuzzi, G, additional, Ruggenenti, P, additional, Saruta, T, additional, Schrader, J, additional, Schrier, R, additional, Sever, P, additional, Sleight, P, additional, Staessen, J A, additional, Suzuki, H, additional, Thijs, L, additional, Ueshima, K, additional, Umemoto, S, additional, van Gilst, W H, additional, Verdecchia, P, additional, Wachtell, K, additional, Whelton, P, additional, Wing, L, additional, Woodward, M, additional, Yui, Y, additional, Yusuf, S, additional, Zanchetti, A, additional, Zhang, Z Y, additional, Anderson, C, additional, Baigent, C, additional, Brenner, BM, additional, Collins, R, additional, de Zeeuw, D, additional, Lubsen, J, additional, Malacco, E, additional, Neal, B, additional, Perkovic, V, additional, Pitt, B, additional, Rodgers, A, additional, Rothwell, P, additional, Salimi-Khorshidi, G, additional, Sundström, J, additional, Turnbull, F, additional, Viberti, G, additional, and Wang, J, additional

Published
2021
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28. Statistics of competing post-breakdown failure modes in ultrathin MOS devices

Author

Sune, Jordi, Wu, Ernest Y., and Lai, Wing L.

Subjects
Breakdown (Electricity) -- Analysis, Reliability (Engineering) -- Analysis, Business, Electronics, Electronics and electrical industries
Abstract

A combination of unstable soft breakdown and progressive hard breakdown failure modes is used to interpret a broad range of dissimilar results in devices with gate oxides ranging from 2.7 to 1 nm. It is found that ultrathin oxides as thin as 1 nm show essentially the same post-breakdown phenomena as oxides above 2 nm.

Published
2006

29. P206 Outcomes of radiologically diagnosed solitary fibrous tumours of the pleura

Author

Mercer, RM, primary, Alqarooni, S, additional, Gurung-Koney, Y, additional, Sharaf, Z, additional, Dack, G, additional, Shatti, D, additional, Edey, A, additional, Arnold, D, additional, Chen, L, additional, Matthews, S, additional, Beresford, H, additional, Cowell, G, additional, Rodrigues, J, additional, Watson, S, additional, Rose, S, additional, Stockbridge, A, additional, Rao, P, additional, Bain, G, additional, Aujayeb, A, additional, Narkhede, P, additional, Wing, L, additional, Benamore, R, additional, and Rahman, NM, additional

Published
2021
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30. Successive oxide breakdown statistics: Correlation effects, reliability methodologies, and their limits

Author

Jordi Sune, Ernest Y. Wu, and Wing L. Lai

Subjects
Metal oxide semiconductors -- Research, Breakdown (Electricity) -- Analysis, Reliability (Engineering) -- Analysis, Business, Electronics, Electronics and electrical industries
Abstract

The statistics of successive oxide breakdown (BD) events in MOS devices is detailed. The application of the successive BD theory to chip reliability assessment is discussed, where several failure criteria and the related reliability methodologies are considered and some of their limits are established.

Published
2004

39. Gene Synthesis

Author

Narang, Saran A., primary, Sung, Wing L., additional, and Wightman, Robert H., additional

Published
2007
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43. Change in Blood Pressure Variability Among Treated Elderly Hypertensive Patients and Its Association With Mortality

Author

Chowdhury, EK, Nelson, MR, Wing, LMH, Jennings, GLR, Beilin, LJ, Reid, CM, Nelson, M, Bruce, A, Beckinsale, P, Thompson, J, McMurchie, M, Fraser, G, Gleave, D, Cope, V, DeLooze, F, Moore, S, Dibben, C, Newbury, J, Miles, H, McDermott, B, Willson, K, Bear, C, West, M, Harrap, S, Johnston, C, Beilin, L, Ryan, P, Wing, L, Reid, C, Brown, M, Jennings, G, Fletcher, P, Feneley, M, Dewar, E, McNeil, J, Marley, J, Moss, J, Webb, P, Glasziou, P, Boyle, F, Primrose, J, Steven, I, Piterman, L, De Looze, F, Dickinson, J, Gambrill, J, Joseph, P, Hunt, D, Donnan, G, Morgan, T, Chalmers, J, Whitworth, J, MacMahon, S, Silagy, C, Chowdhury, EK, Nelson, MR, Wing, LMH, Jennings, GLR, Beilin, LJ, Reid, CM, Nelson, M, Bruce, A, Beckinsale, P, Thompson, J, McMurchie, M, Fraser, G, Gleave, D, Cope, V, DeLooze, F, Moore, S, Dibben, C, Newbury, J, Miles, H, McDermott, B, Willson, K, Bear, C, West, M, Harrap, S, Johnston, C, Beilin, L, Ryan, P, Wing, L, Reid, C, Brown, M, Jennings, G, Fletcher, P, Feneley, M, Dewar, E, McNeil, J, Marley, J, Moss, J, Webb, P, Glasziou, P, Boyle, F, Primrose, J, Steven, I, Piterman, L, De Looze, F, Dickinson, J, Gambrill, J, Joseph, P, Hunt, D, Donnan, G, Morgan, T, Chalmers, J, Whitworth, J, MacMahon, S, and Silagy, C

Abstract

Background Information is scarce regarding effects of antihypertensive medication on blood pressure variability (BPV) and associated clinical outcomes. We examined whether antihypertensive treatment changes BPV over time and whether such change (decline or increase) has any association with long-term mortality in an elderly hypertensive population. Methods and Results We used data from a subset of participants in the Second Australian National Blood Pressure study (n=496) aged ≥65 years who had 24-hour ambulatory blood pressure recordings at study entry (baseline) and then after a median of 2 years while on treatment (follow-up). Weighted day-night systolic BPV was calculated for both baseline and follow-up as a weighted mean of daytime and nighttime blood pressure standard deviations. The annual rate of change in BPV over time was calculated from these BPV estimates. Furthermore, we classified both BPV estimates as high and low based on the baseline median BPV value and then classified BPV changes into stable: low BPV, stable: high BPV, decline: high to low, and increase: low to high. We observed an annual decline (mean±SD: -0.37±1.95; 95% CI, -0.54 to -0.19; P<0.001) in weighted day-night systolic BPV between baseline and follow-up. Having constant stable: high BPV was associated with an increase in all-cause mortality (hazard ratio: 3.03; 95% CI, 1.67-5.52) and cardiovascular mortality (hazard ratio: 3.70; 95% CI, 1.62-8.47) in relation to the stable: low BPV group over a median 8.6 years after the follow-up ambulatory blood pressure monitoring. Similarly, higher risk was observed in the decline: high to low group. Conclusions Our results demonstrate that in elderly hypertensive patients, average BPV declined over 2 years of follow-up after initiation of antihypertensive therapy, and having higher BPV (regardless of any change) was associated with increased long-term mortality.

Published
2019

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