Mineralogical evolution of cement pastes at early ages based on thermogravimetric analysis (TGA)

[EN] Ordinary thermogravimetric analysis (TG) and high-resolution TG tests were carried out on three different Portland cement pastes to study the phases present during the first day of hydration. Tests were run at 1, 6, 12 and 24 h of hydration, in order to determine the phases at these ages. High-resolution TG tests were used to separate decompositions presented in the 100¿200 C interval. The non-evaporable water determined by TG was used to determine hydration degree for the different ages. The effect of particle size distribution (PSD) on mineralogical evolution was established, as well as the addition of calcite as mineralogical filler. Finer PSD and calcite addition accelerate the hydration process, increasing the hydration degree on the first day of eaction between water and cement. According to high-resolution TG results, it was demonstrated that ettringite was the only decomposed phase in the 100¿200 C interval during the first 6 h of hydration for all studied cements. 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age: Observational data from the ICON audit

Purpose: To investigate age-related differences in outcomes of critically ill patients with sepsis around the world.Methods: We performed a secondary analysis of data from the prospective ICON audit, in which all adult ( >16 years ) patients admitted to participating ICUs between May 8 and 18, 2012, were included, except admissions for routine postoperative observation. For this sub-analysis, the 10,012 patients with completed age data were included. They were divided into five age groups - 80 years. Sepsis was defined as infection plus at least one organ failure.Results: A total of 2963 patients had sepsis, with similar proportions across the age groups (80 = 30.9%). Hospital mortality increased with age and in patients >80 years was almost twice that of patients 70 years was independently associated with increased risk of dying.Conclusions: The odds for death in ICU patients with sepsis increased with age with the maximal rate of increase occurring between the ages of 71 and 77 years. (C) 2019 Elsevier Inc. 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Nabil] Ain Shams Fac Med, Cairo, Egypt.[Hosny, H.] Zaitoun Specialized Hosp, Cairo, Egypt.[Ashraf, A.] Gums, Tehran, Iran.[Mokhtari, M.] Sbums, Imam Hossein Hosp, Tehran, Iran.[Nowruzinia, S.] Imamreza Hosp, Mashhad, Razavi Khorasan, Iran.[Lotfi, A.] Laleh Hosp, Tehran, Iran.[Zand, F.] Shiraz Anesthesiol & Crit Care Res Ctr, Shiraz, Iran.[Nikandish, R.] Shiraz Univ Med Sci, Shiraz, Iran.[Moghaddam, O. Moradi] Tehran Med Sci Univ, Tehran, Iran.[Cohen, J.] Rabin Med Ctr, Petah Tiqwa, Israel.[Sold, O.] Sourasky Tel Aviv Med Ctr, Tel Aviv, Israel.[Sfeir, T.] Ctr Hosp Nord, Ettelbruck, Luxembourg.[Hasan, A.] Sohar Hosp, Sohar, Oman.[Abugaber, D.] Specialized Arab Hosp, Nablus, Palestine.[Ahmad, H.] Almana Gen Hosp, Khobar, Saudi Arabia.[Tantawy, T.] KFSHRC, Riyadh, Saudi Arabia.[Baharoom, S.] King Abdulaziz Med City Riyadh, Riyadh, Saudi Arabia.[Algethamy, H.] King Abdulaziz Univ, Jeddah, Saudi Arabia.[Amr, A.] King Saud Med City, Riyadh, Saudi Arabia.[Almekhlafi, G.] Riyadh Mil Hosp, Riyadh, Saudi Arabia.[Coskun, R.] Erciyes Univ, Med Fac, Kayseri, Turkey.[Sungur, M.] Erciyes Univ, Med Sch, Kayseri, Turkey.[Cosar, A.] Gulhane Mil Med Acad, Ankara, Turkey.[Gucyetmez, B.] Int Hosp, Istanbul, Turkey.[Demirkiran, O.] Istanbul Univ, Cerrahpasa Med Sch Hosp, Istanbul, Turkey.[Senturk, E.] Istanbul Univ, Istanbul Med Fac, Istanbul, Turkey.[Ulusoy, H.] Karadeniz Tech Univ, Med Fac, Trabzon, Turkey.[Atalan, H.] Mem Atasehir Hosp, Istanbul, Turkey.[Serin, S.] Pamukkale Univ, Denizli, Turkey.[Kati, I] Yuzuncu Yil Univ, Med Fac, Van, Turkey.[Alnassrawi, Z.] Dubai Hosp, Dubai, U Arab Emirates.[Almemari, A.] Mafraq Hosp, Abu Dhabi, U Arab Emirates.[Krishnareddy, K.] Sheikh Khalifa Med City, Abu Dhabi, U Arab Emirates.[Kashef, S.] Tawam Hosp, Al Ain, U Arab Emirates.[Alsabbah, A.] City Hosp, Dubai, U Arab Emirates.[Poirier, G.] Hop Charles Lemoyne, Longueuil, PQ, Canada.[Marshall, J.] St Michaels Hosp, Toronto, ON, Canada.[Herridge, M.] Toronto Gen Hosp, Toronto, ON, Canada.[Herridge, M.] Toronto Western Hosp, Toronto, ON, Canada.[Fernandez-Medero, R.] San Juan Hosp, San Juan, PR USA.[Fulda, G.] Christiana Care Hlth Syst, Newark, DE USA.[Banschbach, S.] Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH 45229 USA.[Quintero, J.] El Camino Hosp, Mountain View, CA USA.[Schroeder, E.] George Washington Hosp, Washington, DC USA.[Sicoutris, C.] Hosp Univ Penn, Philadelphia, PA 19104 USA.[Gueret, R.] John H Stroger Hosp Cook Cty, Chicago, IL USA.[Kashyap, R.] Mayo Clin, CCM, Rochester, MN USA.[Bauer, P.] Mayo Clin, PCC, Rochester, MN USA.[Nanchal, R.] Med Coll Wisconsin, Milwaukee, WI 53226 USA.[Wunderink, R.] Northwestern Mem Hosp, Chicago, IL 60611 USA.[Jimenez, E.] Orlando Reg Med Ctr Inc, Orlando, FL USA.[Ryan, A.] Washington Hosp Ctr, Washington, DC 20010 USA.[Ryan, A.] Washington Hosp Ctr, 2H, Washington, DC USA.[Ryan, A.] Washington Hosp Ctr, 2G, Washington, DC USA.[Ryan, A.] Washington Hosp Ctr, 3H, Washington, DC USA.[Ryan, A.] Washington Hosp Ctr, 3G, Washington, DC USA.[Ryan, A.] Washington Hosp Ctr, 4H, Washington, DC USA.[Ryan, A.] Washington Hosp Ctr, CVRR, Washington, DC USA.[Prince, D.] Armadale Hlth Serv, Mount Nasura, WA, Australia.[Edington, J.] Bendigo Hosp, Bendigo, Vic, Australia.[Van Haren, F.] Canberra Hosp, Canberra, ACT, Australia.[Bersten, A.] Flinders Med Ctr, Bedford Pk, SA, Australia.[Hawkins, D. J.] Joondalup Hlth Campus, Joondalup, WA, Australia.[Kilminster, M.] Lismore Base Hosp, Lismore, NSW, Australia.[Sturgess, D.] Mater Adult Hosp, South Brisbane, Qld, Australia.[Ziegenfuss, M.] Prince Charles Hosp, Brisbane, Qld, Australia.[O'Connor, S.] Royal Adelaide Hosp, Adelaide, SA, Australia.[Lipman, J.] Royal Brisbane & Womens Hosp, Brisbane, Qld, Australia.[Campbell, L.] Royal Darwin Hosp, Tiwi, NT, Australia.[Mcallister, R.] Royal Hobart Hosp, Hobart, Tas, Australia.[Roberts, B.] Sir Charles Gairdner Hosp, Nedlands, WA, Australia.[Williams, P.] Queen Elizabeth Hosp, Woodville, SA, Australia.[Parke, R.] Auckland Dist Hlth Board, Auckland, New Zealand.[Seigne, P.] Christchurch Hosp, Christchurch, New Zealand.[Freebairn, R.] Hawkes Bay Hosp, Hastings, New Zealand.[Nistor, D.] Palmerston North Hosp, Midcent Hlth, Palmerston North, New Zealand.[Oxley, C.] Middlemore Hosp, Auckland, New Zealand.[Young, P.] Wellington Hosp, Wellington, New Zealand.[Valentini, R.] Cemic, Buenos Aires, DF, Argentina.[Wainsztein, N.] Fleni, Buenos Aires, DF, Argentina.[Comignani, P.] Hosp Aleman, Buenos Aires, DF, Argentina.[Casaretto, M.] Hosp Cent San Isidro, Buenos Aires, DF, Argentina.[Sutton, G.] Hosp Fernandez, Buenos Aires, DF, Argentina.[Villegas, P.] Hosp Francisco Lopez Lima Area Programa Gen Roca, Gen Roca, Argentina.[Galletti, C.] Sanatorio Allende, Cordoba, Argentina.[Neira, J.] Sanatorio Trinidad Palermo, Buenos Aires, DF, Argentina.[Rovira, D.] Sanatorio Julio Corzo Rosario, Rosario, Santa Fe, Argentina.[Hidalgo, J.] Karl Heusner Mem Hosp, Belize City, Belize.[Hidalgo, J.] Belize Healthcare Partner, Belize City, Belize.[Sandi, F.] Hosp Obrero 1, La Paz, Bolivia.[Caser, E.] Cias Unimed Vitoria, Vitoria, ES, Brazil.[Thompson, M.] Evangelical Hosp Cachoeiro De Itapemirim, Cachoeiro De Itapemirim, Brazil.[D'agostino Dias, M.] Hosp 9 Julho, Sao Paulo, Brazil.[Fontes, L.] Hosp Alcides Carneiro, Petropolis, Brazil.[Lunardi, M.] Hosp Clin Luzia De Pinho Melo, Mogi Das Cruzes, Brazil.[Youssef, N.] Hosp Nacoes Curitiba, Curitiba, Parana, Brazil.[Lobo, S.] Hosp Base Famerp, Sao Jose Do Rio Preto, Brazil.[Silva, R.] Hosp Clin Niteroi, Niteroi, RJ, Brazil.[Sales Jr, J.] Hosp Clin Padre Miguel, Rio De Janeiro, Brazil.[Madeira Campos Melo, L.] Hosp Terapia Intens, Sao Paulo, Brazil.[Oliveira, M.] Hosp Trabalhador, Curitiba, Parana, Brazil.[Fonte, M.] Hosp Esperanza, Olinda, PE, Brazil.[Grion, C.] Hosp Evangel Londrina, Londrina, Brazil.[Feijo, C.] Hosp Geral Fortaleza, Fortaleza, Ceara, Brazil.[Rezende, V] Hosp Geral Roraima, Boa Vista, Brazil.[Assuncao, M.] Hosp Israelita Albert Einstein, Sao Paulo, Brazil.[Neves, A.] Hosp Mater Dei, Belo Horizonte, MG, Brazil.[Gusman, P.; Dalcomune, D.] Hosp Meridional, Cariacica, ES, Brazil.[Teixeira, C.] Hosp Moinhos Vento, Porto Alegre, RS, Brazil.[Kaefer, K.] Hosp Municipal Ruth Cardoso, Balneario, Brazil.[Maia, I] Hosp Nereu Ramos, Florianopolis, SC, Brazil.[Souza Dantas, V] Hosp Pasteur, Rio De Janeiro, Brazil.[Costa Filho, R.] Hosp Pro Cardiaco, Rio De Janeiro, Brazil.[Amorim, F.] Hosp Reg Samambaia, Brasilia, DF, Brazil.[Assef, M.] Hosp Reg Hans Dieter Schmidt, Joinville, Brazil.[Schiavetto, P.] Hosp Santa Casa Campo Mourao, Campo Mourao, PR, Brazil.[Houly, J.] Hosp Santa Paula, Sao Paulo, SP, Brazil.[Houly, J.] Hosp Santapaula, Sao Paulo, Brazil.[Bianchi, F.] Hosp Sao Jose Avai, Itaperuna, RJ, Brazil.[Dias, F.] Hosp Sao Lucas Pucrs, Porto Alegre, RS, Brazil.[Avila, C.] Hosp Sao Vicente Paula, Rio De Janeiro, RJ, Brazil.[Gomez, J.] Hosp Sao Vicente Paulo, Rio De Janeiro, Brazil.[Rego, L.] Hosp Saude Mulher, Belem, Para, Brazil.[Castro, P.] Hosp Tacchini, Bento Goncalves, RS, Brazil.[Passos, J.] Hosp Unimed Costa Do Sol Macae Rj, Macae, RJ, Brazil.[Mendes, C.] Hosp Univ Ufpb Joao Pessoa, Joao Pessoa, Paraiba, Brazil.[Grion, C.] Hosp Univ Londrina, Londrina, Brazil.[Colozza Mecatti, G.] Hosp Univ Sao Francisco, Braganca Paulista, SP, Brazil.[Ferrreira, M.] Santa Casa Caridade Diamantina, Diamantina, MG, Brazil.[Irineu, V] Santa Casa Misericordia Tatui, Tatui, Brazil.[Guerreiro, M.] Sao Francisco de Paula Hosp, Sao Francisco De Paula, RS, Brazil.[Ugarte, S.] Clin Indisa, Providencia, Chile.[Tomicic, V] Clin Las Lilas, Providencia, Chile.[Godoy, C.] Hosp Carlos Van Buren, Valparaiso, Chile.[Samaniego, W.] Hosp Trabajador Santiago, Santiago, Chile.[Escamilla, I] Hosp El Pino, San Bernardo, Chile.[Escamilla, I] Hosp Mutual De Seguridad, Santiago, Chile.[Castro Castro, L.] Ctr Med Imbanaco, Valle Del Cauca, Colombia.[Libreros Duque, G.] Clin Colombia Cali, Cali, Colombia.[Diaz-Guio, D.] Clin Del Cafe, Armenia, Colombia.[Benitez, F.] Clin La Estancia SA, Popayan, Colombia.[Guerra Urrego, A.] Clin Medellin, Medellin, Colombia.[Buitrago, R.] Fdn Clin Shaio, Bogota, Colombia.[Ortiz, G.] Hosp Santa Clara, Bogota, Colomb

GWAS and meta-analysis identifies 49 genetic variants underlying critical COVID-19

Data availability: Downloadable summary data are available through the GenOMICC data site (https://genomicc.org/data). Summary statistics are available, but without the 23andMe summary statistics, except for the 10,000 most significant hits, for which full summary statistics are available. The full GWAS summary statistics for the 23andMe discovery dataset will be made available through 23andMe to qualified researchers under an agreement with 23andMe that protects the privacy of the 23andMe participants. For further information and to apply for access to the data, see the 23andMe website (https://research.23andMe.com/dataset-access/). All individual-level genotype and whole-genome sequencing data (for both academic and commercial uses) can be accessed through the UKRI/HDR UK Outbreak Data Analysis Platform (https://odap.ac.uk). A restricted dataset for a subset of GenOMICC participants is also available through the Genomics England data service. Monocyte RNA-seq data are available under the title ‘Monocyte gene expression data’ within the Oxford University Research Archives (https://doi.org/10.5287/ora-ko7q2nq66). Sequencing data will be made freely available to organizations and researchers to conduct research in accordance with the UK Policy Framework for Health and Social Care Research through a data access agreement. Sequencing data have been deposited at the European Genome–Phenome Archive (EGA), which is hosted by the EBI and the CRG, under accession number EGAS00001007111.Extended data figures and tables are available online at https://www.nature.com/articles/s41586-023-06034-3#Sec21 .Supplementary information is available online at https://www.nature.com/articles/s41586-023-06034-3#Sec22 .Code availability: Code to calculate the imputation of P values on the basis of SNPs in linkage disequilibrium is available at GitHub (https://github.com/baillielab/GenOMICC_GWAS).Acknowledgements: We thank the members of the Banco Nacional de ADN and the GRA@CE cohort group; and the research participants and employees of 23andMe for making this work possible. A full list of contributors who have provided data that were collated in the HGI project, including previous iterations, is available online (https://www.covid19hg.org/acknowledgements).Change history: 11 July 2023: A Correction to this paper has been published at: https://doi.org/10.1038/s41586-023-06383-z. -- In the version of this article initially published, the name of Ana Margarita Baldión-Elorza, of the SCOURGE Consortium, appeared incorrectly (as Ana María Baldion) and has now been amended in the HTML and PDF versions of the article.Copyright © The Author(s) 2023, Critical illness in COVID-19 is an extreme and clinically homogeneous disease phenotype that we have previously shown1 to be highly efficient for discovery of genetic associations2. Despite the advanced stage of illness at presentation, we have shown that host genetics in patients who are critically ill with COVID-19 can identify immunomodulatory therapies with strong beneficial effects in this group3. Here we analyse 24,202 cases of COVID-19 with critical illness comprising a combination of microarray genotype and whole-genome sequencing data from cases of critical illness in the international GenOMICC (11,440 cases) study, combined with other studies recruiting hospitalized patients with a strong focus on severe and critical disease: ISARIC4C (676 cases) and the SCOURGE consortium (5,934 cases). To put these results in the context of existing work, we conduct a meta-analysis of the new GenOMICC genome-wide association study (GWAS) results with previously published data. We find 49 genome-wide significant associations, of which 16 have not been reported previously. To investigate the therapeutic implications of these findings, we infer the structural consequences of protein-coding variants, and combine our GWAS results with gene expression data using a monocyte transcriptome-wide association study (TWAS) model, as well as gene and protein expression using Mendelian randomization. We identify potentially druggable targets in multiple systems, including inflammatory signalling (JAK1), monocyte–macrophage activation and endothelial permeability (PDE4A), immunometabolism (SLC2A5 and AK5), and host factors required for viral entry and replication (TMPRSS2 and RAB2A).GenOMICC was funded by Sepsis Research (the Fiona Elizabeth Agnew Trust), the Intensive Care Society, a Wellcome Trust Senior Research Fellowship (to J.K.B., 223164/Z/21/Z), the Department of Health and Social Care (DHSC), Illumina, LifeArc, the Medical Research Council, UKRI, a BBSRC Institute Program Support Grant to the Roslin Institute (BBS/E/D/20002172, BBS/E/D/10002070 and BBS/E/D/30002275) and UKRI grants MC_PC_20004, MC_PC_19025, MC_PC_1905 and MRNO2995X/1. A.D.B. acknowledges funding from the Wellcome PhD training fellowship for clinicians (204979/Z/16/Z), the Edinburgh Clinical Academic Track (ECAT) programme. This research is supported in part by the Data and Connectivity National Core Study, led by Health Data Research UK in partnership with the Office for National Statistics and funded by UK Research and Innovation (grant MC_PC_20029). Laboratory work was funded by a Wellcome Intermediate Clinical Fellowship to B.F. (201488/Z/16/Z). We acknowledge the staff at NHS Digital, Public Health England and the Intensive Care National Audit and Research Centre who provided clinical data on the participants; and the National Institute for Healthcare Research Clinical Research Network (NIHR CRN) and the Chief Scientist’s Office (Scotland), who facilitate recruitment into research studies in NHS hospitals, and to the global ISARIC and InFACT consortia. GenOMICC genotype controls were obtained using UK Biobank Resource under project 788 funded by Roslin Institute Strategic Programme Grants from the BBSRC (BBS/E/D/10002070 and BBS/E/D/30002275) and Health Data Research UK (HDR-9004 and HDR-9003). UK Biobank data were used in the GSMR analyses presented here under project 66982. The UK Biobank was established by the Wellcome Trust medical charity, Medical Research Council, Department of Health, Scottish Government and the Northwest Regional Development Agency. It has also had funding from the Welsh Assembly Government, British Heart Foundation and Diabetes UK. The work of L.K. was supported by an RCUK Innovation Fellowship from the National Productivity Investment Fund (MR/R026408/1). J.Y. is supported by the Westlake Education Foundation. SCOURGE is funded by the Instituto de Salud Carlos III (COV20_00622 to A.C., PI20/00876 to C.F.), European Union (ERDF) ‘A way of making Europe’, Fundación Amancio Ortega, Banco de Santander (to A.C.), Cabildo Insular de Tenerife (CGIEU0000219140 ‘Apuestas científicas del ITER para colaborar en la lucha contra la COVID-19’ to C.F.) and Fundación Canaria Instituto de Investigación Sanitaria de Canarias (PIFIISC20/57 to C.F.). We also acknowledge the contribution of the Centro National de Genotipado (CEGEN) and Centro de Supercomputación de Galicia (CESGA) for funding this project by providing supercomputing infrastructures. A.D.L. is a recipient of fellowships from the National Council for Scientific and Technological Development (CNPq)-Brazil (309173/2019-1 and 201527/2020-0)