A LPUE (LANDING PER UNIT EFFORT) ANALYSIS OF THE TRAWL FISHERY FOR THE COASTAL SHRIMPS Artemesia longinaris AND Pleoticus muelleri OFF SOUTHERN BRAZIL

The Argentine stiletto shrimp (Artemesia longinaris) and the Argentine red shrimp (Pleoticus muelleri) currently sustain an important fishery in terms of tonnage and revenues in southern Brazil. This study analyzed the factors affecting the abundance of both species through the application of Generalized Linear Models to landing-per-unit-of-effort (LPUE) data of the trawl fleet operating on the main fishing grounds between 1998 and 2005. The main patterns of LPUE variability of both species were attributed do the effect of seasons and annual cycles. Larger yields were obtained in the southern shallow areas of Rio Grande do Sul State. No tendency either to an increase or a decline in stock abundance was observed, but the effort in one year was affected by the success of the captures of the previous year. In the last two years analyzed the abundance and the total captures declined.O camarão-barba-ruça (Artemesia longinaris) e o camarão-santana (Pleoticus muelleri) são espécies que sustentam uma pescaria responsável por elevadas capturas das frotas de camaroeiros no sul do Brasil. Este trabalho teve como objetivo analisar a variabilidade da abundância das duas espécies à variação dos dados de DPUEs da frota de arrasteiros em operação entre 1998 e 2005, por meio do ajuste de Modelos Lineares Generalizados (MLG). As principais variações de abundância das duas espécies estão relacionadas aos ciclos anuais e a temporada de pesca. As áreas rasas ao sul do Rio Grande do Sul proporcionaram maiores rendimentos. Não foram observadas tendências de aumento ou declínio na abundância do estoque, mas o esforço de um determinado ano é condicionado pelo sucesso das capturas do ano anterior. Nos dois últimos anos analisados a abundância e as capturas totais foram reduzidas

Deep-sea shrimps (Decapoda: Aristeidae): new targets of the deep-water trawling fishery in Brazil

Seguindo a recente expansão da pesca brasileira para o talude continental, uma nova pescaria de camarões da família Aristeidae tem se desenvolvido desde meados de 2002. O camarão "carabineiro", Aristaeopsis edwardsiana, é o principal componente das capturas, alcançando 88,4 % da produção total de camarões. Os camarões "moruno", Aristaeomorpha foliacea e "alistado", Aristeus antillensis, compõem frações menores das descargas (9,8 % e 1,8 % respectivamente). Duas áreas principais de pesca foram descobertas na região Sudeste do Brasil (19º - 25ºS) e uma no limite setentrional da ZEE do país (4º - 5ºN). As capturas estiveram concentradas entre as isóbatas de 700 e 750 m. As taxas médias de captura de A. edwardsiana flutuaram entre 6,5 e 9,7 kg.h-1. As outras espécies foram capturadas em taxas consideravelmente menores (0,1 - 0,6 kg.h-1 e 0,1 - 1,3 kg.h-1, respectivamente). Sugere-se uma sazonalidade nas capturas de A. edwardsiana, com valores máximos entre julho e dezembro. Apesar do direcionamento aos camarões, capturas incidentais do caranguejo-real (Chaceon ramosae) alcançaram uma média de 22 % das descargas totais.Following the recent expansion of the Brazilian fishery to slope fishing grounds, a new directed trawl fishery for aristeid shrimps emerged since mid 2002. Aristaeopsis edwardsiana has been the main component of the catches attaining 88.4% of total shrimp production. Aristaeomorpha foliacea and Aristeus antillensis have composed significantly smaller fractions of the landings (9.8 % and 1.8 % respectively). Two main grounds were located in the southeastern region (ca. 19º - 25ºS) and one in the northern border of the Brazilian EEZ (ca. 4º30' - 5ºN). Catches have been extremely concentrated between the 700 and 750 m isobaths. Mean catch rates of A. edwardsiana oscillated between 6.5 and 9.7 kg.h-1. The other species have been caught at considerably lower rates (0.1 - 0.6 kg.h-1 and 0.1 - 1.3 kg.h-1, respectively). A seasonal pattern in A. edwardsiana catches is suggested, with maximum values obtained between July and December. While largely directed to the shrimps, incidental catches of the royal crab (Chaceon ramosae) attained, on average, 22 % of the total landings

Arabidopsis Heat Stress-Induced Proteins Are Enriched in Electrostatically Charged Amino Acids and Intrinsically Disordered Regions

[EN] Comparison of the proteins of thermophilic, mesophilic, and psychrophilic prokaryotes has revealed several features characteristic to proteins adapted to high temperatures, which increase their thermostability. These characteristics include a profusion of disulfide bonds, salt bridges, hydrogen bonds, and hydrophobic interactions, and a depletion in intrinsically disordered regions. It is unclear, however, whether such differences can also be observed in eukaryotic proteins or when comparing proteins that are adapted to temperatures that are more subtly different. When an organism is exposed to high temperatures, a subset of its proteins is overexpressed (heat-induced proteins), whereas others are either repressed (heat-repressed proteins) or remain unaffected. Here, we determine the expression levels of all genes in the eukaryotic model system Arabidopsis thaliana at 22 and 37 degrees C, and compare both the amino acid compositions and levels of intrinsic disorder of heat-induced and heat-repressed proteins. We show that, compared to heat-repressed proteins, heat-induced proteins are enriched in electrostatically charged amino acids and depleted in polar amino acids, mirroring thermophile proteins. However, in contrast with thermophile proteins, heat-induced proteins are enriched in intrinsically disordered regions, and depleted in hydrophobic amino acids. Our results indicate that temperature adaptation at the level of amino acid composition and intrinsic disorder can be observed not only in proteins of thermophilic organisms, but also in eukaryotic heat-induced proteins; the underlying adaptation pathways, however, are similar but not the same.D.A.-P. and F.F. were supported by funds from the University of Nevada, Reno, and by pilot grants from Nevada INBRE (P20GM103440) and the Smooth Muscle Plasticity COBRE from the University of Nevada, Reno (5P30GM110767-04), both funded by the National Institute of General Medical Sciences (National Institutes of Health). M.X.R.-G. and M.A.F. were supported by grants from Science Foundation Ireland (12/IP/1637) and the Spanish Ministerio de Economia y Competitividad, Spain (MINECO-FEDER; BFU201236346 and BFU2015-66073-P) to MAF. MXRG was supported by a JAE DOC fellowship from the MINECO, Spain. F.V.-S. and M.A.P.-A. were supported by grant BIO2014-55946-P from MINECO-FEDER.Alvarez-Ponce, D.; Ruiz-González, M.; Vera Sirera, FJ.; Feyertag, F.; Perez Amador, MA.; Fares Riaño, MA. (2018). Arabidopsis Heat Stress-Induced Proteins Are Enriched in Electrostatically Charged Amino Acids and Intrinsically Disordered Regions. International Journal of Molecular Sciences. 19(8). https://doi.org/10.3390/ijms19082276S198Karshikoff, A., & Ladenstein, R. (2001). Ion pairs and the thermotolerance of proteins from hyperthermophiles: a ‘traffic rule’ for hot roads. Trends in Biochemical Sciences, 26(9), 550-557. doi:10.1016/s0968-0004(01)01918-1Strop, P., & Mayo, S. L. (2000). Contribution of Surface Salt Bridges to Protein Stability†,‡. Biochemistry, 39(6), 1251-1255. doi:10.1021/bi992257jPERUTZ, M. F., & RAIDT, H. (1975). Stereochemical basis of heat stability in bacterial ferredoxins and in haemoglobin A2. Nature, 255(5505), 256-259. doi:10.1038/255256a0Argos, P., Rossmann, M. G., Grau, U. M., Zuber, H., Frank, G., & Tratschin, J. D. (1979). Thermal stability and protein structure. Biochemistry, 18(25), 5698-5703. doi:10.1021/bi00592a028Beeby, M., O’Connor, B. D., Ryttersgaard, C., Boutz, D. R., Perry, L. J., & Yeates, T. O. (2005). The Genomics of Disulfide Bonding and Protein Stabilization in Thermophiles. PLoS Biology, 3(9), e309. doi:10.1371/journal.pbio.0030309Haney, P. J., Badger, J. H., Buldak, G. L., Reich, C. I., Woese, C. R., & Olsen, G. J. (1999). Thermal adaptation analyzed by comparison of protein sequences from mesophilic and extremely thermophilic Methanococcus species. Proceedings of the National Academy of Sciences, 96(7), 3578-3583. doi:10.1073/pnas.96.7.3578Kreil, D. P. (2001). Identification of thermophilic species by the amino acid compositions deduced from their genomes. Nucleic Acids Research, 29(7), 1608-1615. doi:10.1093/nar/29.7.1608Tekaia, F., Yeramian, E., & Dujon, B. (2002). Amino acid composition of genomes, lifestyles of organisms, and evolutionary trends: a global picture with correspondence analysis. Gene, 297(1-2), 51-60. doi:10.1016/s0378-1119(02)00871-5Zeldovich, K. B., Berezovsky, I. N., & Shakhnovich, E. I. (2007). Protein and DNA Sequence Determinants of Thermophilic Adaptation. PLoS Computational Biology, 3(1), e5. doi:10.1371/journal.pcbi.0030005Chakravarty, S., & Varadarajan, R. (2000). Elucidation of determinants of protein stability through genome sequence analysis. FEBS Letters, 470(1), 65-69. doi:10.1016/s0014-5793(00)01267-9Cambillau, C., & Claverie, J.-M. (2000). Structural and Genomic Correlates of Hyperthermostability. Journal of Biological Chemistry, 275(42), 32383-32386. doi:10.1074/jbc.c000497200Burra, P. V., Kalmar, L., & Tompa, P. (2010). Reduction in Structural Disorder and Functional Complexity in the Thermal Adaptation of Prokaryotes. PLoS ONE, 5(8), e12069. doi:10.1371/journal.pone.0012069Wang, J., Yang, Y., Cao, Z., Li, Z., Zhao, H., & Zhou, Y. (2013). The Role of Semidisorder in Temperature Adaptation of Bacterial FlgM Proteins. Biophysical Journal, 105(11), 2598-2605. doi:10.1016/j.bpj.2013.10.026Vicedo, E., Schlessinger, A., & Rost, B. (2015). Environmental Pressure May Change the Composition Protein Disorder in Prokaryotes. PLOS ONE, 10(8), e0133990. doi:10.1371/journal.pone.0133990Galea, C. A., High, A. A., Obenauer, J. C., Mishra, A., Park, C.-G., Punta, M., … Kriwacki, R. W. (2009). Large-Scale Analysis of Thermostable, Mammalian Proteins Provides Insights into the Intrinsically Disordered Proteome. Journal of Proteome Research, 8(1), 211-226. doi:10.1021/pr800308vTsvetkov, P., Myers, N., Moscovitz, O., Sharon, M., Prilusky, J., & Shaul, Y. (2012). Thermo-resistant intrinsically disordered proteins are efficient 20S proteasome substrates. Mol. BioSyst., 8(1), 368-373. doi:10.1039/c1mb05283gGalea, C. A., Nourse, A., Wang, Y., Sivakolundu, S. G., Heller, W. T., & Kriwacki, R. W. (2008). Role of Intrinsic Flexibility in Signal Transduction Mediated by the Cell Cycle Regulator, p27Kip1. Journal of Molecular Biology, 376(3), 827-838. doi:10.1016/j.jmb.2007.12.016Van Noort, V., Bradatsch, B., Arumugam, M., Amlacher, S., Bange, G., Creevey, C., … Bork, P. (2013). Consistent mutational paths predict eukaryotic thermostability. BMC Evolutionary Biology, 13(1), 7. doi:10.1186/1471-2148-13-7Wang, G.-Z., & Lercher, M. J. (2010). Amino acid composition in endothermic vertebrates is biased in the same direction as in thermophilic prokaryotes. BMC Evolutionary Biology, 10(1), 263. doi:10.1186/1471-2148-10-263Windisch, H. S., Lucassen, M., & Frickenhaus, S. (2012). Evolutionary force in confamiliar marine vertebrates of different temperature realms: adaptive trends in zoarcid fish transcriptomes. BMC Genomics, 13(1), 549. doi:10.1186/1471-2164-13-549Albanèse, V., Yam, A. Y.-W., Baughman, J., Parnot, C., & Frydman, J. (2006). Systems Analyses Reveal Two Chaperone Networks with Distinct Functions in Eukaryotic Cells. Cell, 124(1), 75-88. doi:10.1016/j.cell.2005.11.039Berry, J., & Bjorkman, O. (1980). Photosynthetic Response and Adaptation to Temperature in Higher Plants. Annual Review of Plant Physiology, 31(1), 491-543. doi:10.1146/annurev.pp.31.060180.002423Sueoka, N. (1961). CORRELATION BETWEEN BASE COMPOSITION OF DEOXYRIBONUCLEIC ACID AND AMINO ACID COMPOSITION OF PROTEIN. Proceedings of the National Academy of Sciences, 47(8), 1141-1149. doi:10.1073/pnas.47.8.1141Cherry, J. L. (2009). Highly Expressed and Slowly Evolving Proteins Share Compositional Properties with Thermophilic Proteins. Molecular Biology and Evolution, 27(3), 735-741. doi:10.1093/molbev/msp270The amino acid composition is different between the cytoplasmic and extracellular sides in membrane proteins. (1992). FEBS Letters, 303(2-3), 141-146. doi:10.1016/0014-5793(92)80506-cNakashima, H., & Nishikawa, K. (1994). Discrimination of Intracellular and Extracellular Proteins Using Amino Acid Composition and Residue-pair Frequencies. Journal of Molecular Biology, 238(1), 54-61. doi:10.1006/jmbi.1994.1267Dosztanyi, Z., Csizmok, V., Tompa, P., & Simon, I. (2005). IUPred: web server for the prediction of intrinsically unstructured regions of proteins based on estimated energy content. Bioinformatics, 21(16), 3433-3434. doi:10.1093/bioinformatics/bti541Peng, Z., Uversky, V. N., & Kurgan, L. (2016). Genes encoding intrinsic disorder in Eukaryota have high GC content. Intrinsically Disordered Proteins, 4(1), e1262225. doi:10.1080/21690707.2016.1262225Yruela, I., & Contreras-Moreira, B. (2013). Genetic recombination is associated with intrinsic disorder in plant proteomes. BMC Genomics, 14(1), 772. doi:10.1186/1471-2164-14-772Paliy, O., Gargac, S. M., Cheng, Y., Uversky, V. N., & Dunker, A. K. (2008). Protein Disorder Is Positively Correlated with Gene Expression inEscherichia coli. Journal of Proteome Research, 7(6), 2234-2245. doi:10.1021/pr800055rSingh, G. P., & Dash, D. (2008). How expression level influences the disorderness of proteins. Biochemical and Biophysical Research Communications, 371(3), 401-404. doi:10.1016/j.bbrc.2008.04.072Yang, J.-R., Liao, B.-Y., Zhuang, S.-M., & Zhang, J. (2012). Protein misinteraction avoidance causes highly expressed proteins to evolve slowly. Proceedings of the National Academy of Sciences, 109(14), E831-E840. doi:10.1073/pnas.1117408109Hendsch, Z. S., & Tidor, B. (1994). Do salt bridges stabilize proteins? A continuum electrostatic analysis. Protein Science, 3(2), 211-226. doi:10.1002/pro.5560030206Zhou, X.-X., Wang, Y.-B., Pan, Y.-J., & Li, W.-F. (2007). Differences in amino acids composition and coupling patterns between mesophilic and thermophilic proteins. Amino Acids, 34(1), 25-33. doi:10.1007/s00726-007-0589-xCatanzano, F., Barone, G., Graziano, G., & Capasso, S. (1997). Thermodynamic analysis of the effect of selective monodeamidation at asparagine 67 in ribonuclease A. Protein Science, 6(8), 1682-1693. doi:10.1002/pro.5560060808Charlesworth, B. (2009). Effective population size and patterns of molecular evolution and variation. Nature Reviews Genetics, 10(3), 195-205. doi:10.1038/nrg2526Bolser, D., Staines, D. M., Pritchard, E., & Kersey, P. (2016). Ensembl Plants: Integrating Tools for Visualizing, Mining, and Analyzing Plant Genomics Data. Methods in Molecular Biology, 115-140. doi:10.1007/978-1-4939-3167-5_6Kasprzyk, A. (2003). EnsMart: A Generic System for Fast and Flexible Access to Biological Data. Genome Research, 14(1), 160-169. doi:10.1101/gr.1645104Hooper, C. M., Castleden, I. R., Tanz, S. K., Aryamanesh, N., & Millar, A. H. (2016). SUBA4: the interactive data analysis centre for Arabidopsis subcellular protein locations. Nucleic Acids Research, 45(D1), D1064-D1074. doi:10.1093/nar/gkw1041R: A language and environment for statistical computing. R Foundation for Statistical Computinghttp://www.R-project.org/Kim, S. (2015). ppcor: An R Package for a Fast Calculation to Semi-partial Correlation Coefficients. Communications for Statistical Applications and Methods, 22(6), 665-674. doi:10.5351/csam.2015.22.6.66

Effect of natalizumab on disease progression in secondary progressive multiple sclerosis (ASCEND). a phase 3, randomised, double-blind, placebo-controlled trial with an open-label extension

Background: Although several disease-modifying treatments are available for relapsing multiple sclerosis, treatment effects have been more modest in progressive multiple sclerosis and have been observed particularly in actively relapsing subgroups or those with lesion activity on imaging. We sought to assess whether natalizumab slows disease progression in secondary progressive multiple sclerosis, independent of relapses. Methods: ASCEND was a phase 3, randomised, double-blind, placebo-controlled trial (part 1) with an optional 2 year open-label extension (part 2). Enrolled patients aged 18–58 years were natalizumab-naive and had secondary progressive multiple sclerosis for 2 years or more, disability progression unrelated to relapses in the previous year, and Expanded Disability Status Scale (EDSS) scores of 3·0–6·5. In part 1, patients from 163 sites in 17 countries were randomly assigned (1:1) to receive 300 mg intravenous natalizumab or placebo every 4 weeks for 2 years. Patients were stratified by site and by EDSS score (3·0–5·5 vs 6·0–6·5). Patients completing part 1 could enrol in part 2, in which all patients received natalizumab every 4 weeks until the end of the study. Throughout both parts, patients and staff were masked to the treatment received in part 1. The primary outcome in part 1 was the proportion of patients with sustained disability progression, assessed by one or more of three measures: the EDSS, Timed 25-Foot Walk (T25FW), and 9-Hole Peg Test (9HPT). The primary outcome in part 2 was the incidence of adverse events and serious adverse events. Efficacy and safety analyses were done in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, number NCT01416181. Findings: Between Sept 13, 2011, and July 16, 2015, 889 patients were randomly assigned (n=440 to the natalizumab group, n=449 to the placebo group). In part 1, 195 (44%) of 439 natalizumab-treated patients and 214 (48%) of 448 placebo-treated patients had confirmed disability progression (odds ratio [OR] 0·86; 95% CI 0·66–1·13; p=0·287). No treatment effect was observed on the EDSS (OR 1·06, 95% CI 0·74–1·53; nominal p=0·753) or the T25FW (0·98, 0·74–1·30; nominal p=0·914) components of the primary outcome. However, natalizumab treatment reduced 9HPT progression (OR 0·56, 95% CI 0·40–0·80; nominal p=0·001). In part 1, 100 (22%) placebo-treated and 90 (20%) natalizumab-treated patients had serious adverse events. In part 2, 291 natalizumab-continuing patients and 274 natalizumab-naive patients received natalizumab (median follow-up 160 weeks [range 108–221]). Serious adverse events occurred in 39 (13%) patients continuing natalizumab and in 24 (9%) patients initiating natalizumab. Two deaths occurred in part 1, neither of which was considered related to study treatment. No progressive multifocal leukoencephalopathy occurred. Interpretation: Natalizumab treatment for secondary progressive multiple sclerosis did not reduce progression on the primary multicomponent disability endpoint in part 1, but it did reduce progression on its upper-limb component. Longer-term trials are needed to assess whether treatment of secondary progressive multiple sclerosis might produce benefits on additional disability components. Funding: Biogen

Seafood Consumption, Omega-3 Fatty Acids Intake, and Life-Time Prevalence of Depression in the PREDIMED-Plus Trial

Background: The aim of this analysis was to ascertain the type of relationship between fish and seafood consumption, omega-3 polyunsaturated fatty acids (ω-3 PUFA) intake, and depression prevalence. Methods: Cross-sectional analyses of the PREDIMED-Plus trial. Fish and seafood consumption and ω-3 PUFA intake were assessed through a validated food-frequency questionnaire. Self-reported life-time medical diagnosis of depression or use of antidepressants was considered as outcome. Depressive symptoms were collected by the Beck Depression Inventory-II. Logistic regression models were used to estimate the association between seafood products and ω-3 PUFA consumption and depression. Multiple linear regression models were fitted to assess the association between fish and long-chain (LC) ω-3 PUFA intake and depressive symptoms. Results: Out of 6587 participants, there were 1367 cases of depression. Total seafood consumption was not associated with depression. The odds ratios (ORs) (95% confidence intervals (CIs)) for the 2nd, 3rd, and 4th quintiles of consumption of fatty fish were 0.77 (0.63–0.94), 0.71 (0.58–0.87), and 0.78 (0.64–0.96), respectively, and p for trend = 0.759. Moderate intake of total LC ω-3 PUFA (approximately 0.5–1 g/day) was significantly associated with a lower prevalence of depression. Conclusion: In our study, moderate fish and LC ω-3 PUFA intake, but not high intake, was associated with lower odds of depression suggesting a U-shaped relationship

CIBERER : Spanish national network for research on rare diseases: A highly productive collaborative initiative

Altres ajuts: Instituto de Salud Carlos III (ISCIII); Ministerio de Ciencia e Innovación.CIBER (Center for Biomedical Network Research; Centro de Investigación Biomédica En Red) is a public national consortium created in 2006 under the umbrella of the Spanish National Institute of Health Carlos III (ISCIII). This innovative research structure comprises 11 different specific areas dedicated to the main public health priorities in the National Health System. CIBERER, the thematic area of CIBER focused on rare diseases (RDs) currently consists of 75 research groups belonging to universities, research centers, and hospitals of the entire country. CIBERER's mission is to be a center prioritizing and favoring collaboration and cooperation between biomedical and clinical research groups, with special emphasis on the aspects of genetic, molecular, biochemical, and cellular research of RDs. This research is the basis for providing new tools for the diagnosis and therapy of low-prevalence diseases, in line with the International Rare Diseases Research Consortium (IRDiRC) objectives, thus favoring translational research between the scientific environment of the laboratory and the clinical setting of health centers. In this article, we intend to review CIBERER's 15-year journey and summarize the main results obtained in terms of internationalization, scientific production, contributions toward the discovery of new therapies and novel genes associated to diseases, cooperation with patients' associations and many other topics related to RD research

Sloan Digital Sky Survey IV: Mapping the Milky Way, Nearby Galaxies, and the Distant Universe

We describe the Sloan Digital Sky Survey IV (SDSS-IV), a project encompassing three major spectroscopic programs. The Apache Point Observatory Galactic Evolution Experiment 2 (APOGEE-2) is observing hundreds of thousands of Milky Way stars at high resolution and high signal-to-noise ratios in the near-infrared. The Mapping Nearby Galaxies at Apache Point Observatory (MaNGA) survey is obtaining spatially resolved spectroscopy for thousands of nearby galaxies (median $z\sim 0.03$). The extended Baryon Oscillation Spectroscopic Survey (eBOSS) is mapping the galaxy, quasar, and neutral gas distributions between $z\sim 0.6$ and 3.5 to constrain cosmology using baryon acoustic oscillations, redshift space distortions, and the shape of the power spectrum. Within eBOSS, we are conducting two major subprograms: the SPectroscopic IDentification of eROSITA Sources (SPIDERS), investigating X-ray AGNs and galaxies in X-ray clusters, and the Time Domain Spectroscopic Survey (TDSS), obtaining spectra of variable sources. All programs use the 2.5 m Sloan Foundation Telescope at the Apache Point Observatory; observations there began in Summer 2014. APOGEE-2 also operates a second near-infrared spectrograph at the 2.5 m du Pont Telescope at Las Campanas Observatory, with observations beginning in early 2017. Observations at both facilities are scheduled to continue through 2020. In keeping with previous SDSS policy, SDSS-IV provides regularly scheduled public data releases; the first one, Data Release 13, was made available in 2016 July

Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (Harmony Outcomes): a double-blind, randomised placebo-controlled trial

Background: Glucagon-like peptide 1 receptor agonists differ in chemical structure, duration of action, and in their effects on clinical outcomes. The cardiovascular effects of once-weekly albiglutide in type 2 diabetes are unknown. We aimed to determine the safety and efficacy of albiglutide in preventing cardiovascular death, myocardial infarction, or stroke. Methods: We did a double-blind, randomised, placebo-controlled trial in 610 sites across 28 countries. We randomly assigned patients aged 40 years and older with type 2 diabetes and cardiovascular disease (at a 1:1 ratio) to groups that either received a subcutaneous injection of albiglutide (30–50 mg, based on glycaemic response and tolerability) or of a matched volume of placebo once a week, in addition to their standard care. Investigators used an interactive voice or web response system to obtain treatment assignment, and patients and all study investigators were masked to their treatment allocation. We hypothesised that albiglutide would be non-inferior to placebo for the primary outcome of the first occurrence of cardiovascular death, myocardial infarction, or stroke, which was assessed in the intention-to-treat population. If non-inferiority was confirmed by an upper limit of the 95% CI for a hazard ratio of less than 1·30, closed testing for superiority was prespecified. This study is registered with ClinicalTrials.gov, number NCT02465515. Findings: Patients were screened between July 1, 2015, and Nov 24, 2016. 10 793 patients were screened and 9463 participants were enrolled and randomly assigned to groups: 4731 patients were assigned to receive albiglutide and 4732 patients to receive placebo. On Nov 8, 2017, it was determined that 611 primary endpoints and a median follow-up of at least 1·5 years had accrued, and participants returned for a final visit and discontinuation from study treatment; the last patient visit was on March 12, 2018. These 9463 patients, the intention-to-treat population, were evaluated for a median duration of 1·6 years and were assessed for the primary outcome. The primary composite outcome occurred in 338 (7%) of 4731 patients at an incidence rate of 4·6 events per 100 person-years in the albiglutide group and in 428 (9%) of 4732 patients at an incidence rate of 5·9 events per 100 person-years in the placebo group (hazard ratio 0·78, 95% CI 0·68–0·90), which indicated that albiglutide was superior to placebo (p<0·0001 for non-inferiority; p=0·0006 for superiority). The incidence of acute pancreatitis (ten patients in the albiglutide group and seven patients in the placebo group), pancreatic cancer (six patients in the albiglutide group and five patients in the placebo group), medullary thyroid carcinoma (zero patients in both groups), and other serious adverse events did not differ between the two groups. There were three (<1%) deaths in the placebo group that were assessed by investigators, who were masked to study drug assignment, to be treatment-related and two (<1%) deaths in the albiglutide group. Interpretation: In patients with type 2 diabetes and cardiovascular disease, albiglutide was superior to placebo with respect to major adverse cardiovascular events. Evidence-based glucagon-like peptide 1 receptor agonists should therefore be considered as part of a comprehensive strategy to reduce the risk of cardiovascular events in patients with type 2 diabetes. Funding: GlaxoSmithKline