51 research outputs found
Rice Straw Geotextile As Ground Cover ForSoil Erosion Mitigation
- Author
- Publication venue
- Journal of Energy Technologies and Policy
- Publication date
- 25/11/2013
- Field of study
Generally, the study aimed to mitigate soil erosion using rice straw geotextile as ground cover. Specifically, it attempted to: evaluate the effect of RSM and RSN as ground cover in mitigating soil erosion at varying slope gradients and different rainfall intensities, and; determine the relationship of slope gradient versus sediment concentration, sediment yield and quantity of soil loss at different levels of rainfall intensity. Results revealed that RSGT as ground cover greatly affected soil erosion. Under rainfall intensities of 75, 100 and 125 mm/hr, RSM had significantly lower soil loss as compared to RSN, CCN And NGC. However, RSN and CCN were comparable with each other but differ significantly with NGC. Sediment concentration, sediment yield and soil erosion exhibited a nonlinear relationship with slope gradient. At any given level of rainfall intensity, the three indicators increased correspondingly as the slope was increased from 10 to 35o and then declined when the slope was further increased from 35 to 60o. Sediment concentration best fitted (R2 = 0.977) in a quadratic model in the form of a second-degree polynomial equation: SC = 0.551 + 0.626S - 0.008S2 Likewise, observed sediment yield best fitted (R2 = 0.954) a second degree polynomial equation as expressed by a quadratic model: SY = 356.0 + 61.70S â 0.972S2 Moreover, the observed soil erosion was best modeled with R2 = 97.1% confidence by a second degree polynomial equation. The regression model is quadratic in form and is given by the equation: SE = 68.92 + 11.11S - 0.174S2. Keywords: rice straw, geotextile, ground cover, soil erosion, mitigation, rainfall simulatio
Occupational Safety and Health Practices among Physical Therapists in Metro Manila during the COVID-19 Pandemic: A Qualitative Study Protocol
- Author
- Publication venue
- SOAR @ USA
- Publication date
- 31/03/2023
- Field of study
Introduction: The purpose of Occupational Safety and Health (OSH) is to protect and prevent workers from being exposed to risks and hazards that are detrimental to their health and safety. For the past two years, the coronavirus disease 2019 (COVID-19) is one of the most significant occupational health outcomes to physical therapists (PTs) due to the nature of their work. However, minimal studies have been conducted about the experiences and OSH practices of PTs during the pandemic. This study aims to understand the experiences of clinical PTs in Metro Manila, Philippines during the pandemic. The study also seeks to explore the OSH practices and responses of PTs to presenting occupational risks and hazards through a qualitative descriptive study design.
Methods: In this qualitative descriptive study, a maximum variation purposeful sampling method will be used in recruiting an estimated total of twelve (12) participants. A preliminary questionnaire would be disseminated via Google Forms to determine the eligibility of potential participants. Data will be gathered through a one-to-one semi-structured online interview, which will be transcribed verbatim and recorded with audio and video. Both manual coding and software-aided coding (NVivo) will be utilized in the data analysis. Emerging themes will be identified using thematic inductive analysis.
Discussion: The results of the study may contribute to the formulation of better guidelines in handling infectious diseases even after quarantine restrictions are lifted. Furthermore, the findings will also provide the groundwork for the local body of knowledge in the Philippines and may serve as a future reference for research concerning OSH practices in physical therapy locally
Cross-Sectional Dating of Novel Haplotypes of HERV-K 113 and HERV-K 115 Indicate These Proviruses Originated in Africa before Homo sapiens
- Author
- A. R. Jha
- Altschul
- Bannert
- Barbulescu
- Belshaw
- Bulmer
- Burmeister
- Clark
- Contreras-Galindo
- Corpet
- Costas
- D. F. Nixon
- D. J. Wachter
- E. C. Storm
- E. R. Sharp
- Ehlhardt
- Garrison
- Gifford
- Golan
- Herrera
- Ho
- J. N. Martin
- Johnson
- K. E. Garrison
- Kimura
- Lander
- Lavie
- LÂ Â wer
- M. G. Rosenberg
- Macfarlane
- Marguerat
- Mariani-Costantini
- Mayer
- McDougall
- Moyes
- Noonan
- Otowa
- Reus
- Rozen
- S. G. Deeks
- S. K. Pillai
- Sicat
- Steinhuber
- Turner
- V. A. York
- Wang-Johanning
- Publication venue
- Oxford University Press
- Publication date
- 01/11/2009
- Field of study
The human genome, human endogenous retroviruses (HERV), of which HERV-K113 and HERV-K115 are the only known full-length proviruses that are insertionally polymorphic. Although a handful of previously published papers have documented their prevalence in the global population; to date, there has been no report on their prevalence in the United States population. Here, we studied the geographic distribution of K113 and K115 among 156 HIV-1+ subjects from the United States, including African Americans, Hispanics, and Caucasians. In the individuals studied, we found higher insertion frequencies of K113 (21%) and K115 (35%) in African Americans compared with Caucasians (K113 9% and K115 6%) within the United States. We also report the presence of three single nucleotide polymorphism sites in the K113 5âČ long terminal repeats (LTRs) and four in the K115 5âČ LTR that together constituted four haplotypes for K113 and five haplotypes for K115. HERV insertion times can be estimated from the sequence differences between the 5âČ and 3âČ LTR of each insertion, but this dating method cannot be used with HERV-K115. We developed a method to estimate insertion times by applying coalescent inference to 5âČ LTR sequences within our study population and validated this approach using an independent estimate derived from the genetic distance between K113 5âČ and 3âČ LTR sequences. Using our method, we estimated the insertion dates of K113 and K115 to be a minimum of 800,000 and 1.1 million years ago, respectively. Both these insertion dates predate the emergence of anatomically modern Homo sapiens
Enterprises in the Philippines: Dynamism and Constraints to Employment Growth
- Author
- Publication venue
- 'Elsevier BV'
- Publication date
- 01/01/2013
- Field of study
Whole-genome sequencing reveals host factors underlying critical COVID-19
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- Abd Elghafar M. S.
- Abdel-Aziz M.
- Abdelrazik M.
- Abdollahi H.
- Abdullah T.
- Abecasis G. R.
- Abedalthagafi M.
- Abel L.
- Abernathy C.
- Abraheem A.
- Abul-Husn N. S.
- Acquilini D.
- Adams C.
- Adams E. L.
- Adams K.
- Adamsara A.
- Adanini O.
- Adeleye O.
- Adra D.
- Afilalo J.
- Afilalo M.
- Afolabi D.
- Afrasiabi Z.
- Agasou A.
- Agrawal S.
- Aguero D.
- Ahmad N.
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- Ahmed A.
- Ahmed C.
- Akeroyd L.
- Akhtar M. N.
- Akinkugbe O.
- Aksentijevich A.
- Al-Afghani H.
- Al-Awdah L.
- Alaamery M.
- Alahmadey Z. Z.
- Alaverdian D.
- Alavere H.
- Albader A.
- Albaiceta G. M.
- Albakri J. K.
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- Albeladi M.
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- Albrich W.
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- Aleagha A. E.
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- Tang L.
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- Tariq A.
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- Taylor M.
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- Tilney E.
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- Ting L.
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- Torrents D.
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- Tyler A.
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- Underwood S. J.
- Vaghi M.
- Vaida M.
- Valente S.
- Valentine J.
- Valentino F.
- van Blokland I.
- van Heel D. A.
- van Koutrik L.
- Varghese M.
- Vecchia M.
- Vedage D.
- Veerapen K.
- Venkatesh H.
- Venn L. D.
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- Verma A.
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- Vincent R.
- Vincenti A.
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- Vizcaychipi M. P.
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- von Frenckell C.
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- Vuylsteke A.
- Wackett T.
- Wadams B.
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- Wagstaff V.
- Wain L. V.
- Waite A. A. C.
- Wakefield P.
- Wakinshaw F.
- Waldron J.
- Walker D.
- Walker R.
- Walker S.
- Walker S.
- Wall A.
- Walsh T.
- Walters R. K.
- Walton O.
- Wang B.
- Wang J.
- Wang X.
- Wanying Z.
- Ward G.
- Ward L.
- Ward M.
- Warden S.
- Warmerdam R.
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- Watkins C.
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- Watson G.
- Watson J.
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- Weaver J.
- Webster A.
- Webster D.
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- Weston H.
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- Wyllie D. H.
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- Yadav A.
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- Zollner S.
- Zongo O.
- Zucchi P.
- Zyndorf M.
- Publication venue
- 'Springer Science and Business Media LLC'
- Publication date
- 01/01/2022
- Field of study
Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2â4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genesâincluding reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)âin critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease
The Dynamics of the Regulation of Labor in Developing and Developed Countries since 1960
- Author
- A Alesina
- A Alesina
- A Arpaia
- A Banks
- A Bassanini
- A Cosar
- A Drazen
- A Drazen
- A Forteza
- A Muravyev
- A Reutersward
- A Winters
- B Greenhill
- B Macleod
- C Calderïżœn
- C Montenegro
- D &
- D Birmingham
- D Grubb
- D Kucera
- Di Tella
- E &
- E Amadeo
- E Artuc
- E Villegas
- G Allard
- G Allard
- G Bertola
- G Bertola
- G Haddad
- G R C G Nicoletti
- G Sicat
- H Frundt
- H Ladjevardi
- I Saif
- J Addison
- J Addison
- J Agell
- J Botero
- J Heckman
- J Heckman
- Jeffrey B. Nugent
- La Porta
- M &
- M &
- M &
- M Aleksynska
- M Pripstein
- N Campos
- Natlex
- Nauro F. Campos
- O Blanchard
- Oecd
- P &
- P Fallon
- Peter R Fallon
- R Barros
- R Brooks
- R Freeman
- R Freeman
- R Wacziarg
- S Deakin
- S Djankov
- S Djankov
- S Nickell
- S Nickell
- T &
- T Beck
- T Boeri
- V Acharya
- W Eichhorst
- W Henisz
- World Bank
- World Bank
- Publication venue
- 'Elsevier BV'
- Publication date
- 01/01/2012
- Field of study
This paper examines both the determinants and the effects of changes in the rigidity of labor market legislation across countries over time. Recent research identifies the origin of the legal system as being a major determinant of the cross-country variation in the rigidity of employment protection legislation. However, the supporting evidence is largely confined to levels of regulation and is almost exclusively based on international cross-section data for the post-1995 period. This paper introduces a new index capturing the rigidity of employment protection legislation (LAMRIG) for an unbalanced panel of more than 140 countries over time starting in 1960. Although the importance of legal origins in explaining the level of rigidity of labor regulations across countries is replicated using LAMRIG, their explanatory power is much weakened for changes over time (1960-2004.) More important as determinants of such changes are the level of development and other reforms such as trade liberalization. With respect to the effects of changes in the rigidity of labor regulations on growth and inequality, which have been very controversial in the literature, results with LAMRIG support Freemanâs conjecture that changes in rigidity do not systematically affect economic growth but do lower income inequality.http://deepblue.lib.umich.edu/bitstream/2027.42/133054/1/wp1037.pd
Endogenous retrovirus-K promoter: a landing strip for inflammatory transcription factors?
- Author
- A Dupressoir
- A Flockerzi
- A Imhof
- A Inui
- A Koito
- A Ray
- A Serafino
- A Yarilina
- A Zaravinos
- AC van der Kuyl
- AJ Adler
- AK Tai
- AP Armstrong
- B Barbeau
- B Bonetti
- B Krone
- BC Hoopes
- BH Cai
- BM Laoide
- BS Rubin
- C Esnault
- C Loh
- C Toufaily
- CE Massie
- CY Lin
- D Bayarsaihan
- D Morgan
- D SenGupta
- D Taruscio
- D Wong
- DE Levy
- E Anderson
- E Kovalskaya
- E Soldaini
- F Cedeno-Laurent
- F de Nigris
- F Rosenbauer
- F Ryan
- F Wang-Johanning
- F Wang-Johanning
- FC Hsiao
- G Castellano
- G Freimanis
- H Maier
- H Ryu
- HB Urnovitz
- HJ Cho
- HJ Kwun
- I Arany
- I Katoh
- IA Maksakova
- J Nishikawa
- J Paces
- J Sicat
- J Song
- J Sugimoto
- JD Kim
- JD MacMicking
- JK Chan
- JP Garay
- JS Handen
- K Buscher
- K Hanke
- K Ikuta
- K Khodosevich
- K Ruprecht
- K Stopak
- K Yamamoto
- KD Carroll
- KH Fischbeck
- KM Providence
- L Ferraris
- L Lavie
- L Li
- L Muniz
- L Wang
- LD Vales
- M Golan
- M Kearse
- M Knossl
- M Krzysztalowska-Wawrzyniak
- M Ono
- M Pizzi
- M Sgarbanti
- MA Nead
- MA Schwarzschild
- Mamneet Manghera
- MJ Gonzalez-Hernandez
- N Sutkowski
- N Sutkowski
- NV Fuchs
- O Frank
- O Frank
- P Hatzis
- P Perot
- P Yin
- PJ Roche
- QL Deng
- R Contreras-Galindo
- R Contreras-Galindo
- R Contreras-Galindo
- R Douville
- R Lin
- RB Jones
- RE Randall
- Renée N Douville
- RP Subramanian
- RW Holdaft
- S Harroch
- S Landry
- S Philipsen
- S Solyom
- SE Wang
- SF Sleiman
- SS Mukhopadhyay
- T Christensen
- T Tchenio
- T Wang
- TD Halazonetis
- V Andres
- V Blikstad
- W Seifarth
- W Sui
- WJ Lee
- X Messeguer
- XR Mao
- Y He
- Y Lavrosky
- Y Stauffer
- YM Jiang
- YN Lee
- Z Li
- ZX Jin
- Publication venue
- 'Springer Science and Business Media LLC'
- Publication date
- Field of study
Genetic mechanisms of critical illness in COVID-19.
- Author
- A A Roger Thompson
- A Abraheem
- A Agasou
- A Ahmed
- A Ali
- A Allan
- A Altabaibeh
- A Alvaro
- A Aspinwall
- A Ayers
- A Bamford
- A Barron
- A Bashyal
- A Bellini
- A Bociek
- A Botello
- A Bowes
- A Brady
- A Brayne
- A Brown
- A Brown
- A Butler
- A Campbell
- A Carter
- A Collins
- A Cowley
- A Cowton
- A Cowton
- A Cox
- A Crew
- A Dance
- A Daniel
- A Daniels
- A Dela Rosa
- A Drummond
- A Durie
- A E Heron
- A Easthope
- A Easthope
- A Evans
- A Fofano
- A Gales
- A Ganesan
- A Gardner
- A Garg
- A Gherman
- A Gordon
- A Gratrix
- A Gulati
- A Gupta
- A Haigh
- A Haldeos
- A Harrison
- A Harvey
- A Hayes
- A Higham
- A Higham
- A Hilldrith
- A Holden
- A Hormis
- A Hutcheon
- A Javaid
- A Joseph
- A Kaliappan
- A Katary
- A Kay
- A Kayani
- A Kent
- A Kirkby
- A Knight
- A Kubisz-Pudelko
- A Kuravi
- A Lewis
- A Loveridge
- A Lyle
- A Mayer
- A McAlpine
- A McCarthy
- A McGregor
- A McGregor
- A Meikle
- A Mitchell
- A Mitra
- A Morris
- A Morrison
- A Naranjo
- A Nicholson
- A Nicholson
- A Nilsson
- A Noakes
- A Patel
- A Pickard
- A Poole
- A Price
- A Puxty
- A Quinn
- A Quinn
- A Raithatha
- A Rattray
- A Reddy
- A Reed
- A Reyes
- A Rose
- A Rose
- A Rostron
- A Roy
- A Roynon-Reed
- A S Raj
- A Salberg
- A Sanderson
- A Serrano-Ruiz
- A Solesbury
- A Sukha
- A Swain
- A Tariq
- A Thomas
- A Thomas
- A Todd
- A Tomas
- A Tridente
- A Tucci
- A Turnbull
- A Uriel
- A Ustianowski
- A Vochin
- A Vuylsteke
- A Waite
- A Walden
- A Whileman
- A Wilkinson
- A Williams
- A Williams
- A Wilson
- A Zak
- A Zaki
- Achille Iolascon
- Adam Auton
- Adam Brown
- Agnese Verzuri
- Agostino Ognibene
- Agostino Riva
- Ailsa Golightly
- Alan Maclean
- Alessandra
- Alessandra Stella
- Alessandra Vergori
- Alessia Giorli
- Alexander J Mentzer
- Alice Donati
- Alison M Meynert
- Alistair Nichol
- Ana da Silva Filipe
- Andrea Antinori
- Andrea Cossarizza
- Andrea Ganna
- Andrea Tommasi
- Andrew Rambaut
- Andrew Stenhouse
- Andy Law
- Anjali J Shastri
- Anna Canaccini
- Anna Maria Pinto
- Annarita Giliberti
- Annemarie B Docherty
- Antonella D'Arminio Monforte
- Antonia Ying Wai Ho
- Antonio Di Biagio
- Antony Symons
- Arianna Emiliozzi
- Arianna Gabrieli
- Audrey Coutts
- B Anwar
- B Attwood
- B Baines
- B Blackledge
- B Borislavova
- B Chandler
- B Charles
- B Creagh-Brown
- B David
- B Deacon
- B Deacon
- B Digby
- B Faulkner
- B Fuller
- B Gumbrill
- B Gurung
- B Hadebe
- B Hairsine
- B Hopkins
- B Johnston
- B Lenagh
- B Masunda
- B Ogg
- B Patel
- B Player
- B Purewal
- B Scholefield
- B Shelley
- B Sloan
- B Thomas
- B Wadams
- B Welsh
- B Wilkinson
- B Winter-Goodwin
- B Yates
- Baillie J Kenneth
- Barbara Rossetti
- Beale Rupert
- Beatrice Alex
- Benjamin Bach
- Bretherick Andrew D
- Bruno Frediani
- C Adams
- C Ahmed
- C Almaden-Boyle
- C Ashbrook-Raby
- C Basikolo
- C Battle
- C Beazley
- C Beith
- C Borra
- C Brandwood
- C Brantwood
- C Burnett
- C Castro Delgado
- C Clark
- C Clulow
- C Collins
- C Cruz
- C Davis
- C Demetriou
- C Dennis
- C Dexter
- C Downes
- C Dunmore
- C Eastgate
- C Eckbad
- C Finch
- C Gibson
- C Gorman
- C Hays
- C Hewitt
- C Holl
- C Howcroft
- C Humphrey
- C Jackson
- C Jardine
- C Jennings
- C Jones
- C Kaye
- C Lynch
- C Lyons
- C McCulloch
- C McParland
- C McParland
- C Murphy
- C Parmar
- C Pawley
- C Phillips
- C Phillips
- C Pothecary
- C Pothecary
- C Prendergast
- C Price
- C Rishton
- C Sell
- C Shovelton
- C Sicat
- C Stuart
- C Summers
- C Swan
- C Thompson
- C Thorpe
- C Tibke
- C Tierney
- C Vigurs
- C Wells
- C Whitton
- C Whyte
- C Wrey Brown
- Cameron J Fairfield
- Carmelo Piscopo
- Carmen Marciano
- Caroline Abernathy
- Carrol Gamble
- Caterina Lo Rizzo
- Catherine A Shaw
- Catherine H Weldon
- Caulfield Mark
- Ceilia Boz
- Cesira Nencioni
- Chelsea Ye
- Chiara Fallerini
- Chiara Gabbi
- Chiara Spertilli
- Chloe Donohue
- Chris Ponting
- Christoper A Green
- Cinthia E Jannes
- Clare Jackson
- Clohisey Sara
- Cristina Mussini
- D Antcliffe
- D Bakthavatsalam
- D Banach
- D Baptista
- D Bell
- D Branney
- D Brealey
- D Brealey
- D Butcher
- D Butcher
- D Childs
- D Clarke
- D Collier
- D Collier
- D Cristiano
- D Dawson
- D Donaldson
- D Duffin
- D Fottrell-Gould
- D Golden
- D Griffin
- D Hamilton
- D Hawcutt
- D Hope
- D Horner
- D Kallon
- D Kaye
- D Kelly
- D Loader
- D Lomas
- D Martin
- D McGlynn
- D McLaughlanv
- D Melia
- D Menzies
- D Mullan
- D Pogson
- D Potla
- D Potoczna
- D Purohit
- D Raynard
- D Salutous
- D Salutous
- D Scaletta
- D Shaw
- D Skinner
- D Smyth
- D Strachan
- D Tetla
- D Thornton
- D Trodd
- D Vedage
- D Walker
- D Warren
- D Williams
- D Wood
- D Wright
- Daniela Francisci
- Daniella Coker
- Danilo Tacconi
- David A van Heel
- David Bennet
- David L Robertson
- David Stuart
- Dawn Law
- Debby Bogaert
- Derek Murphy
- Domenico A Coviello
- E Abaleke
- E Allan
- E Anastasescu
- E Andrews
- E Apetri
- E B Jude
- E Beech
- E Beranova
- E Bevan
- E Black
- E Brinkworth
- E Collins
- E Combes
- E Davies
- E Dobson
- E Dooks
- E Fisher
- E Gendall
- E Goff
- E Goodwin
- E Gordon
- E Heeney
- E Horsley
- E Hughes
- E Johnson
- E Knights
- E Lee
- E London
- E Maccacari
- E Massey
- E McKenna
- E Meadows
- E Moncur
- E Morino
- E Mwaura
- E Peasgood
- E Perkins
- E Radford
- E Raith
- E Raith
- E Salciute
- E Smith
- E Smithson
- E Stoddard
- E Stones
- E Thomas
- E Tilney
- E Timlick
- E Treus Gude
- E Virgilio
- E Watson
- E Wilby
- Edoardo Conticini
- Egle Saviciute
- Elena Bargagli
- Elena Desanctis
- Elisa Benetti
- Elisa Frullanti
- Elisabetta Menatti
- Elisabetta Schiaroli
- Ellie Mcmaster
- Emma C Thomson
- Emmanuelle Marques
- Enrico Martinelli
- Esther Duncan
- Esther Merlini
- Ewen M Harrison
- F Anderson
- F Auld
- F Bibi
- F Davies
- F Farquhar
- F Fisher
- F Hurford
- F Kibutu
- F McNeela
- F Moore
- F Nasir
- F Trim
- F Wakinshaw
- F Williams
- Fabio Lena
- Fawkes Angie
- Federico Anedda
- Federico Franchi
- Ferdinando Giannattasio
- Filip Taneski
- Filippo Aucella
- Filippo Biscarini
- Floriana Valentino
- Fourman Max Head
- Francesca Andretta
- Francesca Fava
- Francesca Gatti
- Francesca Mari
- Francesca Montagnani
- Francesco Castelli
- Francesco Raimondi
- Furniss James
- G Andrew
- G Arbane
- G Bell
- G Bercades
- G Croston
- G Debreceni
- G Durrant
- G Hambrook
- G Hobden
- G Houston
- G Hughes
- G Jones
- G Lubimbi
- G Maloney
- G Martir
- G Millen
- G Mills
- G O'Connor
- G Padden
- G Randell
- G Sadera
- G Seddon
- G Sera Howe
- G Sloane
- G Subramanian
- G Tsinaslanidis
- G Turner
- G Watson
- G Wray
- Gabriella Coiro
- Gabriella Doddato
- Gail Carson
- Gardar Sveinbjornsson
- Gary Leeming
- Genni Spargi
- Georgios Pollakis
- Giacomo Zanelli
- Gian Piero Caldarelli
- Giancarlo Bosio
- Giuseppe Fiorentino
- Giuseppe Merla
- Gountouna Elvina
- Graham S Cooke
- Griffiths Fiona
- Grimes Graeme
- H Bancroft
- H Bates
- H Belfield
- H Blackman
- H Blakemore
- H Brooke
- H Button
- H Coles
- H Curgenven
- H Filipe
- H Fox
- H Golding
- H Hill
- H Holcombe
- H Houlden
- H Jeffrey
- H Kent
- H Langton
- H McGuinness
- H Meghari
- H Millward
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- Sophie Venturelli
- Stefania Mantovani
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- Stefano Rusconi
- Stella Aslibekyan
- Stephanie Roberts
- Stephen R Knight
- Summers Charlotte
- Susanna Croci
- Susanna Guerrini
- T Anderson
- T Arden
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- T Behan
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- T Wood
- Tammy Gilchrist
- Tenesa Albert
- Teresa Filshtein-Sonmez
- Thomas M Drake
- Thushan de Silva
- Tim Walsh
- Tom Fletcher
- Tom Solomon
- Tony Wackett
- Trevor Paterson
- Tullio Trotta
- Turtle Lance
- U Poultney
- V Amin
- V Anumakonda
- V Bastion
- V Cannons
- V Crickmore
- V Gopal
- V Irvine
- V Kasipandian
- V Krishnamurthy
- V Lake
- V Linnett
- V Martinson
- V Nagarajan
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- V Parris
- V Parris
- V Pristopan
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- V Sarathy
- V Thomas
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- V Tuckey
- V Turner
- V Wagstaff
- V Waugh
- Valentina Anemoli
- Vanessa Sancho-Shimizu
- Victoria Shaw
- Vitart Veronique
- W Harrison
- W Khaliq
- W Khaliq
- W McCormick
- W Woodyatt
- Walker Susan
- Walsh Timothy
- Wang Bo
- Wei Shen Lim
- Wendy S Barclay
- William A Paxton
- William Greenhalf
- Wilson James F
- Wrobel Nicola
- Wu Yang
- X Qiu
- Y Baird
- Y Choudhury
- Y Hussain
- Y Jackson
- Y Thirlwall
- Yang Jian
- Yang Zhijian
- Z Alldis
- Z Belagodu
- Z Bradshaw
- Z Coton
- Z Daly
- Z Farzad
- Z Fernandez
- Z Garland
- Z Maqsood
- Z Omar
- Z Prime
- Z Scott
- Zechner Marie
- Zhai Ranran
- Zheng Chenqing
- Publication venue
- Nature
- Publication date
- 01/01/2020
- Field of study
Host-mediated lung inflammation is present1, and drives mortality2, in the critical illness caused by coronavirus disease 2019 (COVID-19). Host genetic variants associated with critical illness may identify mechanistic targets for therapeutic development3. Here we report the results of the GenOMICC (Genetics Of Mortality In Critical Care) genome-wide association study in 2,244 critically ill patients with COVID-19 from 208 UK intensive care units. We have identified and replicated the following new genome-wide significant associations: on chromosome 12q24.13 (rs10735079, PÂ =Â 1.65Â ĂÂ 10-8) in a gene cluster that encodes antiviral restriction enzyme activators (OAS1, OAS2 and OAS3); on chromosome 19p13.2 (rs74956615, PÂ =Â 2.3Â ĂÂ 10-8) near the gene that encodes tyrosine kinase 2 (TYK2); on chromosome 19p13.3 (rs2109069, PÂ =Â 3.98Â ĂÂ Â 10-12) within the gene that encodes dipeptidyl peptidase 9 (DPP9); and on chromosome 21q22.1 (rs2236757, PÂ =Â 4.99Â ĂÂ 10-8) in the interferon receptor gene IFNAR2. We identified potential targets for repurposing of licensed medications: using Mendelian randomization, we found evidence that low expression of IFNAR2, or high expression of TYK2, are associated with life-threatening disease; and transcriptome-wide association in lung tissue revealed that high expression of the monocyte-macrophage chemotactic receptor CCR2 is associated with severe COVID-19. Our results identify robust genetic signals relating to key host antiviral defence mechanisms and mediators of inflammatory organ damage in COVID-19. Both mechanisms may be amenable to targeted treatment with existing drugs. However, large-scale randomized clinical trials will be essential before any change to clinical practice
Whole-genome sequencing reveals host factors underlying critical COVID-19
- Author
- Abd Elghafar M.S.
- Abdel-Aziz M.
- Abdelrazik M.
- Abdollahi H.
- Abdullah T.
- Abecasis G.R.
- Abecasis G.R.
- Abedalthagafi M.
- Abel L.
- Abernathy C.
- Abraheem A.
- Abul-Husn N.S.
- Acquilini D.
- Adams C.
- Adams E.L.
- Adams K.
- Adamsara A.
- Adanini O.
- Adeleye O.
- Adra D.
- Afilalo J.
- Afilalo M.
- Afolabi D.
- Afrasiabi Z.
- Agasou A.
- Agrawal S.
- AgĂŒero D.
- Ahmad N.
- Ahmadi S.
- Ahmed A.
- Ahmed C.
- Akeroyd L.
- Akhtar M.N.
- Akinkugbe O.
- Aksentijevich A.
- Al Harthi F.
- Al Mutairi A.
- Al-Afghani H.
- Al-Awdah L.
- Alaamery M.
- Alahmadey Z.Z.
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- Albader A.
- Albaiceta G.M.
- Albakri J.K.
- AlBardis H.
- Albeladi M.
- Albesher N.
- Albrich W.
- AlDhawi N.
- Aldridge J.
- Aleagha A.E.
- Alexander P.
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- Alghamdi B.
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- Ali A.
- Ali A.
- Ali I.A.M.
- Ali S.
- Aliannejad R.
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- AlJohani S.
- Alkwai S.
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- Bartley S.
- Baruah R.
- Bashyal A.
- Basikolo C.
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- Zhou W.
- Zitter L.
- Zlatopolsky M.
- Zongo O.
- Zucchi P.
- Zyndorf M.
- Zöllner S.
- Ă svold B.O.
- Publication venue
- Springer Science and Business Media LLC
- Publication date
- 07/07/2022
- Field of study
Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2,3,4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genesâincluding reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)âin critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease
Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19
- Author
- ?ivko Iris
- Abbass Hakam
- Abdeladim Lilia
- Abdelhady Hesham
- Abdelkharim Hussam
- Abdelrazik Marwa
- Abdi Zakee
- Abdukahil Sheryl Ann
- Abel Lynn
- Abraham Jacinta
- Abrahamson Gail
- Abusamra Yousuf
- Aceto Romina
- Adams Nick
- Adams Peter
- Adebambo Olumide
- Adhikari Neill
- Adhikari Sheetal
- Affleck Julia
- Agha Gloria
- Aghemo Alessio
- Agno Ronan
- Ahmad Norfaizan
- Ain Quratul
- Ainscough Kate
- Ainsworth James
- Aitken Lindianne
- Akamp Ceren
- Al Enezi Farhan
- Al-Bassam Wisam
- Al-Beidh Farah
- Albert Martin
- Albrett Jonathan
- Alderman Meera
- Aldo Bonizzoni Matteo
- Alegria Ana
- Alessandro CarĂ Gianmarco
- Alexander Brian
- Alexander Peter
- Alfonso Jordan
- Ali Maryam
- Ali Murtaza
- Allam Hayat
- Allen Barbara
- Allen Louise
- Allibone Suzanne
- Almeshhedani Hasham
- AlQahtani Samah
- Alswaidan Lolowa
- Altomy Mohammed
- Al Amri Ali
- Al Qasim Eman
- Amatya Sameena
- Ambrosino Richard
- Anderson Thomas
- Andreae Mark
- Aneman Anders
- Angus Derek C.
- Anjum Aisha
- Ankert Juliane
- Annane Djillali
- Anne-Laure Fedou
- Anstey Matthew
- Antcliffe David
- Anthony Alpha
- Antoine Marchalot
- Antoine Pierre
- Antoine Studer
- Anumakonda Vikram
- Aparicio Christelle
- Aquino Maia
- Arabi Yaseen M.
- Arachchige Malka
- Aravindan Latha
- Arbane Gill
- Archambault Patrick
- Archer Simon
- Aref Noah
- Arias Ana-Marie
- Arias Sonia
- Arishi Hatim
- Arnold Donald
- Arnold John
- Arnott Andrew
- Arora Anand
- Aryal Diptesh
- Asghar Adeeba
- Asif Namra
- Aspinwall Angelique
- Attokaran Antony
- Attwood Ben
- Au Carly
- Audry Mathilde
- Austin Karen
- Austin Pauline
- Auvet Adrien
- Avard Bronwyn
- Awan Sidra
- Ayee Robert
- Azaiz Amine
- Azzaui Harun
- Babu Suresh
- Bacon Gina
- Badalamenti Salvatore
- Badie Julio
- Bagavathy Kavitha
- Bagot Catherine
- Bagshaw Sean
- Baig Nadia
- Baikady Ravishankar
- Bailey Lucy
- Baillie Kenneth
- Bain William
- Baker Alice
- Baker Evelyn
- Baker Stuart
- Bakthavatsalam Dhanalakshmi
- Balaie Morteza
- Balls-Burgess Sam
- Bamford Amy
- Bamford Peter
- Banach Dorota
- Bannard-Smith Jonathan
- Barbash Ian
- Barber Russell
- Barbier François
- Barge Deborah
- Bariola Ryan
- Barker Gareth
- Barker Stephanie
- Barnes Nicky
- Baron Rebecca M.
- Barreau Amelie
- Barreau Amélie
- Bart Robert
- Bartholomew Jazz
- Bartley Shauna
- Barton David
- Barton Frances
- Bashyal Archana
- Basile Kim
- Bass Frances
- Bassford Christopher
- Bastos Joana Margarida Pereira Sousa
- Bates Michelle
- Bates Samantha
- Batista Teresa Margarida Oliveira
- Bauchmuller Kris
- Bayne Madeleine
- Bean Sarah
- Beane Abi
- Beane Abigail
- Beard Gregory
- Beasley Richard
- Beaudoin Rosalie
- Beavis Sarah
- Beddows Seonaid
- Bedford Caroline
- Beer Deborah
- Beer Sally
- Begin Phillipe
- Begum Salma
- Bell Gillian
- Bellemare David
- Belletti Allesandro
- Bendjemar Lynda
- Benettaib Fatna
- Bensen Nicole
- Bentley Andrew
- Benyon Sarah
- Benzekri Dalila
- Beqai Besa
- Berdaguer Fernando
- Beresford Stephanie
- Bergin Colin
- Berry Lindsay R.
- Berry Scott
- Berryman Emily
- Bertel Melanie
- Best-Lane Janis
- Besten Henny
- Bevan Emily
- Bewley Jeremy
- Beyerl Ashley
- Bhagani Sanjay
- Bhandal Khushpreet
- Bharaj Kiranjit
- Bhattarai Bina
- Bhattarai Binita
- Bhonagiri Deepak
- Biddie Simon
- Bigas Judit
- Bihari Shailesh
- Bin Hasan Mohd Shahnaz
- Bindels Manon
- Binnie Alexandra
- Biradar Vishwanath
- Birch Catherine
- Birch Janine
- Birch Sophie
- Birchall Kathrine
- Birkinshaw Isobel
- Black Ethel
- Blackledge Bethany
- Blakemore Hayley
- Blanck Wendy
- Bland Yvonne
- Blank Elisabeth
- Bleasdale John
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- Board Jasmin
- Boardman Melanie
- Boari Gianluca
- Bocher Simon
- Bociek Aneta
- Boivin Anne-Helene
- Boivin Anne-HĂ©lĂšne
- Bojunga Jörg
- Bomken Charlotte
- Bonaccorso Allesandra
- Bongaerts Katherine
- Bonner Stephen
- Bonten Marc J. M.
- Borgatta Barbara
- Borislavova Borislava
- Borrill Zoe
- Boschert Catherine
- Bossard Isabelle
- Bothma Pieter
- Boudineau Michel
- Boulanger Marie-Claude
- Boumahni Dounia
- Bouman Angela
- Bounab Rania
- Bourgoin Charlotte
- Bourne Michelle
- Bourne Richard
- Boutin Mireille
- Bouvier Elodie
- Bouw-Ruiter Marianne
- Boué Yvonnick
- Bowen James
- Bowler Helen
- Boyd Craig
- Boyles Rebecca
- Bracke Stephanie
- Bradbury Charlotte A.
- Bradley Paul
- Brady Kara
- Brailsford Jane
- Brain Matthew
- Brakké Karen
- Brant Emily
- Brasselet Aurélie
- Breen Patrick
- Bremmer Pamela
- Brend Morwenna
- Brennan Aoife
- Bretagnol Anne
- Brett Stephen
- Brewer Chris
- Brickell Kathy
- Bridges Sarah
- Brieger Klaus-Gerd
- Brightling Chris
- Brimfield Lutece
- Brittain Michael
- Britton Kate
- Brochard Laurent
- Brodbeck Andreas
- Brohi Farooq
- Brooks Nicole
- Brown Cynthia
- Brown Julia
- Brown Louise
- Brown Nerissa
- Brown Zarah
- Brugman Curt
- Brunetta Enrico
- Brunkhorst Frank M.
- Brunskill Nigel
- Bryan-Morris Kayla
- Bryden Emma
- Budd Joanna
- Buehner Ulrike
- Buhay Megan
- Buhr Heidi
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- Burda Dorota
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- Burke David
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- Burkey Jason
- Burnish Rachel
- Burns Dean
- Burns Karen
- Burrell Aidan
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- Butler Amelia
- Butler Magdalena
- Butler Susan
- Buxton Meredith
- Buzgau Adrian
- Byrne Kathleen
- Byrne Rahim
- Cabrelli Louise
- Cabreros Leilani
- Cairns Tom
- Calfee Carolyn
- Callahan Jean-Christophe
- Cambalova Lenka
- Campbell Andrew
- Campbell Bridget
- Campbell Debbie
- Campbell Hilary
- Campbell Lewis
- Campbell Marion
- Campbell Ryan
- Campion Alexandra
- Campisi Josie
- Camsooksai Julie
- Caplin Cecile
- Carbonneau Elaine
- Carmichael Samantha
- Carmona Rosario
- Carn Vanessa
- Carpio Lillian
- Carr Zoe
- Carr-Wilkinson Joanne
- Carrier François
- Carrier Marc
- Carter Angus
- Carter Brittney
- Carter David
- Carter Jay
- Carter Michael
- Casali Sherry
- Casey Ruth
- Casey Siobhan
- Castelain Vincent
- Castle James
- Cathcart Susanne
- Catorze Nuno José Teodoro Amaro dos Santos
- Cattelan Jessy
- Cavayas Alexandros
- Cawley Kathryn
- Cecconi Maurizio
- Centofanti John
- Chambers Emma
- Champanerkar Shreekant
- Chan Carmen
- Chan Charles
- Chan Peter
- Chapman Rachel
- Chapman Susan
- Charles Bethan
- Charles Walton
- Charlewood Richard
- Charlton Sam
- Charron Cyril
- Chartier Delphine
- Chasse Michael
- Chassé Michaël
- Chen Jonathan
- Chen Lixian
- Chen Yan
- Cheng Allen C.
- Cherian Shiney
- Chhablani Manish
- Chin Teri
- Chudeau Nicolas
- Chukkambotla Sri
- Ciccarelli Michele
- Cirstea Emanuel
- Clair Bernard
- Clark Amy
- Clark Michele
- Clark Richard
- Clark Sarah
- Clarke Frances
- Clarke Jennifer
- Claxton Andrew
- Cleary Joanne
- Clement Ian
- Clere-Jehl Raphael
- Clermont Giles
- Clermont Gilles
- Clinton Alison
- Cloutier Ăve
- Cockrell Maeve
- Codreanu Daniel
- Coetzee Samantha
- Coghlan Phoebe
- Cole Jade
- Coles Jennifer
- Colin Gwenhael
- Collier Dawn
- Collins Amy
- Collins Daniel
- Collins Emma
- Collins Joanne
- Collins Ărin
- Collis Matthew
- Combaux Daniele
- Commons Robert
- Comp Susan
- Concha Pablo
- Connolly Karen
- Constantini Elena
- Constantino-Occhipinti Claudia
- Contou Damien
- Convery Karen
- Conway Robert
- Conzelmann Nadine
- Cook Deborah
- Cook Tim
- Cooke Jill
- Cooke Justin
- Cooper Jamie
- Cooper Josh
- Cooper Lauren
- Cooper Melanie
- Cooper Nichola
- Corbett Sarah
- Corcoran Ele
- Corcoran Kathleen
- Cornell Sarah
- Cornell Thomas
- Cort Jon
- Costerousse Olivier
- Couillard-ChĂ©nard Ămilie
- Courtin Laura
- Coutts Amanda
- Couture Lourie
- Cove Matthew
- Cowdrey Keri-Anne
- Cowley Nicholas
- Cowton Amanda
- Coyne Mark
- Craddock Richard
- Craner Michelle
- Craven Thomas
- Crawshaw Sarah
- Creagh-Brown Ben
- Creange Vanessa
- Cremer Olaf
- Crisp Nikki
- Croft Maria
- Csabi Peter
- Cudlipp Joanna
- Cuesta Jeronimo
- Cuffaro Raffaele
- Curley Gerard
- Currie Andrew
- Cusack Rebecca
- Cuthbertson Brian
- Cutler Sean
- CĂĄrcel Sheila
- CĂŽtĂ© Ămilie
- D?Amato Fabiola
- D?Aragon Frédérick
- Daebis Admad
- Daher Rana
- Dale Katie
- Daley Jessica
- Dalton James
- Daly James
- Daly Zoe
- Daneman Nick
- Dark Paul
- Darnell Robert
- Darreau Cedric
- Daugherty Jason
- Davey Miriam
- Davidson Neil
- Davies Ellie
- Davies Gwyneth
- Davies Jennifer
- Davies Louisa
- Davies Michelle
- Davies Rhys
- Dawson Laura Ann
- Dawvda Ashlish
- Day Christopher
- Da Rocha Joana
- De Bus Liesbet
- de Courcy-Golder Kim
- de Groot Klaas
- de Jong Menno
- de Jonge Evert
- De Keulenaer Bart
- de la Torre Cisneros Julian
- de Man Angelique
- De Neef Mark
- De Smeytere Anouska
- Deacon Bethan
- Dean Steven
- Dean Tessa
- Dearden Joy
- Dechert William
- Declercq Pierre-Louis
- Degracia Anna
- del Sorbo Lorenzo
- Dela Rosa Arnold
- Delaney Kirsha
- Dell Abbie
- del Prado Michael
- Demetriou Carrie
- Dempster Debra
- Denham Lynn
- Denmade Craig
- Dent Martin
- Depante Maria
- Depuydt Pieter
- Dequin Pierre-François
- Derde Lennie P. G.
- Deshpande Kush
- Detry Michelle A.
- Deye Nicolas
- de la Fuente Carmen
- De Waele Jan
- Dheke Krishan
- Di Lucca Giuseppe
- Dias Priya
- Dice Julie
- Digby Stephen
- Diridis Kristina
- Distler Michael
- Dobell-Brown Kelsey
- Doble Patricia
- Dobson Jade
- Doherty Kaleigh
- Doherty Ronan
- Doi Yohei
- Dolman Rozzie
- Domingo-Marco Joana
- Donadee Chenell
- Donaldson Kate
- Dondrop Arjen
- Donegan Clare
- Donlon Sinead
- Donnelly Adrian
- Donnelly Kieran
- Donnison Phil
- Doonan Reece
- Doran Peter
- Dore Rachael
- Dormand Natalie
- Dos Santos Filipa
- Douillard Thomas
- Drake Chelsea
- Drapola Debra
- Drayss Maria
- Drummond Andrew
- Drury Kay
- Duan Erick
- Duberley Stephen
- Duffy Eamon
- Duffy Oscar
- Duke Graeme
- Duke Zoe
- Duncan Tracy
- Dunsavage Janice
- Duplaix Mathilde
- Duric Natalie
- Duroux Maree
- Dushianthan Ahilanandan
- Dyas Sarah
- Eapen Beena
- Eastgate Christine
- Ebenezer R
- Edmunds Natasha
- Edwards Alexandra
- Efford Georgia
- Egreteau Pierre
- Ehrmann Stephan
- Eichenauer Dennis
- Eisenbeis Simone
- Ekhérian Jean-Michel
- El-Khawas Khaled
- Elender Corinna
- Elgendy Ahmad
- Elhassan Munzir
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- Estensen Kristen
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- Fowler Robert
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- Fox Eleonore
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- Frakking Thuy
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- Godoy Lucas C.
- Goebeler M.E.
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- Haider Nafeesah
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- Hall Alistair S
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- Harris Jade
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- Hashmi Madiha
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- HC Ooi
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- Karlikowski Michal
- Karlsson Sari
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- Kassir Sandy
- Katary Amro
- Kato Hideaki
- Kavanagh Lisa
- Kayani Abdul
- Kayastha Srijana
- Kaye Callum
- Kazi Aayesha
- KC Shirish
- KC Shirsh
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- Keatley Claire
- Keeler Sheryl
- Keen Alexandra
- Keen Sherbrina
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- Kendrick Sara
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- Khade Reena
- Khalid Imrana
- Khan Meherunnisa
- Khanal Kishor
- Khanal Sushil
- Khare Divya
- Khoso Nasir
- Khoud Ahmed
- Khwaja Kosar
- Kidwai Aneela
- Kiiski Heikki
- Kilner Mari
- Kim Edy Y.
- Kimpton Sarah
- King Andrew
- Kinney Fiona
- Kirk Jill
- Kirk Rosemary
- Kirkby Amy
- Kirkham Simon
- Kit Barbara
- Kitsios Georgios
- Kittridge Lauren
- Klein Daniela
- Klop-Riehl Margreet
- Kluge Stefan
- Knowles Karen
- Kochanek Matthias
- Kochert Erik
- Koelink Maaike
- Koirala Kanchan
- Koirala Sabin
- Kolanos Steffi
- Kolovou Angeliki
- Konecny Pam
- Kong Jing
- Koopmans Matty
- Kosa Alma
- Kremling Julius
- KreĂ Gabriele
- Krishnamoorthy S
- Krishnamurthy Vinodh
- Kruger Peter
- Kruisdijk-Gerritsen Arriette
- Kruisselbrink Rebecca
- Kuitunen Anne
- Kumar Anand
- Kumar Nikhil
- Kumar Rohit
- Kummerlen Christine
- Kunishima Hiroyuki
- Kunwar Puja
- Kunz Kevin
- Kurenda Catherine
- Kutsogiannis Demetrios
- Kuybida Yuriy
- Kwan Yvonne
- Kyeremeh Lynsey
- Kyle Laura
- L?Hotellier Sylvie
- Labbe Vincent
- Laffan Mike
- Laffey John
- Laha Shondipon
- Lai Vivian
- Lambert Bridget
- Lamontagne Francois
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- Vaara Suvi
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- van Amerongen Roosmarijn
- van Bentum-Puijk Wilma
- van Bree Sjoerd
- van de Veerdonk Frank L.
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- Weissman Alexandra
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- Williams Erin
- Williams Gemma
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- Williamson James D
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- Winters Lauren
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- Wittekamp Bastiaan
- Wittenberg Wendy
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- Woods Lindsey
- Woodward Robert
- Woolett Melissa
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- Wright Chris
- Wright Kim
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- Wyatt Rachel
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- Xavier Kugan
- Yamagishi Yoshiaki
- Yamashita Chizuru
- Yang Yang
- Yarad Elizabeth
- Yates Bryan
- Yates David
- Yealy Donald
- Young Ian
- Young Meredith
- Young Paul
- Youngstein Taryn
- Yu Haili
- Yusuff Hakeem
- Zaharia Mihaela
- Zaidi Abbas
- Zaki Ahmed
- Zaman Mohsin
- Zarychanski Ryan
- Zdanavidiene Ausra
- Zhao Xiao
- Zinzoni Vanessa
- Zitter Letizia
- Zouita Louisa
- Publication venue
- 'American Medical Association (AMA)'
- Publication date
- 11/04/2023
- Field of study
IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19.
Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19.
DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 nonâcritically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022).
INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (nâ=â257), ARB (nâ=â248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; nâ=â10), or no RAS inhibitor (control; nâ=â264) for up to 10 days.
MAIN OUTCOMES AND MEASURES The primary outcome was organ supportâfree days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes.
RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ supportâfree days among critically ill patients was 10 (â1 to 16) in the ACE inhibitor group (nâ=â231), 8 (â1 to 17) in the ARB group (nâ=â217), and 12 (0 to 17) in the control group (nâ=â231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ supportâfree days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively).
CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes.
TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570
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