71 research outputs found
Competitive chlorination of substituted ethylenes
- Author
- Publication venue
- The University of Edinburgh
- Publication date
- 01/01/1967
- Field of study
Investigation of the nature of the oxidant (selective and unselective) in/on a vanadyl pyrophosphate catalyst
- Publication venue
- 'Springer Science and Business Media LLC'
- Publication date
- 01/01/2006
- Field of study
The anaerobic oxidation of CO by a (VO)2P2O7 catalyst has been used to investigate the nature of the oxidant (selective and unselective) in/on that material. Three peaks were observed in the rate of production of CO2 - at 993, 1073 and 1093 K. The temperature of the maximum in the rate of production of the first CO2 peak and the amount of oxygen associated with it are the same as that observed in the selective anaerobic oxidation of n-butane to butene and butadiene, but-1-ene to butadiene and furan and but-1,3-diene to dihydrofuran, furan and maleic anhydride. The interaction of CO with the (VO)2P2O7 catalyst forming CO2 at 993 K is therefore concluded to be with the selective oxygen. The total amount of oxygen removed by the CO from the (VO)2P2O7 lattice (>5 monolayers) is about six times greater than that of the selective oxygen. The higher activation energies for the removal of the unselective oxygen accounts for the high selectivities (~80%) encountered commercially for the anaerobic oxidation of n-butane to maleic anhydride. Re-oxidation of the CO reduced (VO)2P2O7 by N2O quantitatively replaces all of the lattice oxygen removed by the formation of CO2, but does not restore the original morphology
On the mechanism of the selective oxidation of n-butane, but-1-ene and but-1,3-diene to maleic anhydride over a vanadyl pyrophosphate catalyst
- Publication venue
- 'Springer Science and Business Media LLC'
- Publication date
- 04/03/1997
- Field of study
The mechanism of the selective partial oxidation of n-butane, but-1-ene and but-1,3-diene over a vanadyl phosphate catalyst has been investigated by temperature-programmed desorption (TPD) and by anaerobic temperature-programmed oxidation (TPO). TPD showed lattice oxygen to be desorbed in two states at 998 and 1023 K. The anaerobic TPO of n-butane produced butene and butadiene at 1020 K; anaerobic TPO of but-1-ene produced butadiene and furan at 990 K and dehydrofuran at 965 K, while anaerobic TPO of but-1,3-diene produced dehydrofuran at 970 K, furan at 1002 K and maleic anhydride at 1148 K. The total amount of oxygen removed from the lattice in these anaerobic selective partial oxidations was the same as that evolved from the vanadyl phosphate catalyst by TPD. This, and the fact that the selective oxidation reactions occurred at the same temperature at which the oxygen evolves from the lattice, suggests that the lattice oxygen is uniquely selective when it appears at the surface of the catalyst. (Under identical conditions of flow rate, weight of catalyst, heating rate etc., the reaction of n-butane or of but-1,3-diene in air produced only CO2 and H2O.
The association between maternal blood pressures and offspring size at birth in Southeast Asian women
- Author
- A Elvan-Taspinar
- A Shennan
- An Pan
- B Williams
- B Williams
- C Lydakis
- C Mayer
- Chuen-Seng Tan
- D Churchill
- E Hafner
- F Khan
- H Yadav
- J Katz
- J Waugh
- J Zhang
- K Dhall
- KA Harmon
- Keith M Godfrey
- Kenneth Kwek
- KG Alberti
- LA Rahman
- M Fujime
- MS Kramer
- P Kaufmann
- Peter D Gluckman
- PR Romundstad
- R Bakker
- RA Odegard
- RB Ness
- SE Soh
- Seang-Mei Saw
- T Tomimatsu
- TR Everett
- Wai-Yee Lim
- X Xiong
- Yap-Seng Chong
- Yung-Seng Lee
- 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
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- D Collier
- D Collier
- D Cristiano
- D Dawson
- D Donaldson
- D Duffin
- D Fottrell-Gould
- D Golden
- D Griffin
- D Hamilton
- D Hawcutt
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- D Kallon
- D Kaye
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- 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
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- E Goff
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- F Anderson
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- Filip Taneski
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- Furniss James
- G Andrew
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- G Randell
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- G Sloane
- G Subramanian
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- G Turner
- G Watson
- G Wray
- Gabriella Coiro
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- H Bancroft
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- J Dearden
- J Deery
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- J Dykes
- J Easton
- J Egan
- J Fernandez Roman
- J Finn
- J Fletcher
- J Frankham
- J Gaylard
- J Gill
- J Godden
- J Goodsell
- J Gregory
- J Greig
- J Gurasashvili
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- J Harris
- J Hatton
- J Hawes
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- J Hulme
- J Hunt
- J Hutter
- J Ingham
- J Jones
- J Jones
- J K Baillie
- J Kassam
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- J Kenneth Baillie
- J Keshet-Price
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- J Mallinson
- J Martin
- J Matthews
- J McCormick
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- J Moreno Cuesta
- J Morgan
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- J Perez
- J Perry
- J Pheby
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- J Reid
- J Rhodes
- J Riches
- J Ritzema
- J Ruddy
- J Ryan-Smith
- J Scriven
- J Scriven
- J Scriven
- J Shiel
- J Singh
- J Singleton
- J Smith
- J Sowter
- J Strickley
- J Summers
- J Taylor
- J Tebbutt
- J Texeira
- J Thomas
- J Thrush
- J Tomlinson
- J Valentine
- J Whiteside
- J Wilkins
- J Willson
- J Zamikula
- Jake Dunning
- Jane Weaver
- Janet Harrison
- Janet T Scott
- Janie F Shelton
- Jen Meikle
- Jo Dalton
- Johnny Millar
- Jorge Esparza-Gordillo
- Jose E Krieger
- Julian A Hiscox
- K Archer
- K Austin
- K Baines
- K Bauchmuller
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- K Burt
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- K Hanson
- K Hanson
- K Hard
- K Harrington
- K Hayes
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- K Holdroyd
- K Howard
- K Hugill
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- K Netherton
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- K Potts
- K Prager
- K Praman
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- K Pritchard
- K Puxty
- K Reid
- K Riches
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- K Sellick
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- K Simpson
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- K Xavier
- Katarzyna Hafezi
- Keating Sean
- Kenneth A Mclean
- Kirstie Morrice
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- Kousathanas Athanasios
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- Montgomery Hugh
- Moore Shona C
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- Stephanie Roberts
- Stephen R Knight
- Summers Charlotte
- Susanna Croci
- Susanna Guerrini
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- Tenesa Albert
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- Thushan de Silva
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- Tom Solomon
- Tony Wackett
- Trevor Paterson
- Tullio Trotta
- Turtle Lance
- U Poultney
- V Amin
- V Anumakonda
- V Bastion
- V Cannons
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- V Gopal
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- 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, P = 1.65 × 10-8) in a gene cluster that encodes antiviral restriction enzyme activators (OAS1, OAS2 and OAS3); on chromosome 19p13.2 (rs74956615, P = 2.3 × 10-8) near the gene that encodes tyrosine kinase 2 (TYK2); on chromosome 19p13.3 (rs2109069, P = 3.98 × 10-12) within the gene that encodes dipeptidyl peptidase 9 (DPP9); and on chromosome 21q22.1 (rs2236757, P = 4.99 × 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
Measurement of the inclusive isolated-photon cross section in pp collisions at √s = 13 TeV using 36 fb−1 of ATLAS data
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- Abbott B.
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- Abdinov O.
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- Šforza F.
- Ženiš T.
- Živković L.
- Publication venue
- Institute of Physics Publishing
- Publication date
- 01/01/2019
- Field of study
The differential cross section for isolated-photon production in pp collisions is measured at a centre-of-mass energy of 13 TeV with the ATLAS detector at the LHC using an integrated luminosity of 36.1 fb. The differential cross section is presented as a function of the photon transverse energy in different regions of photon pseudorapidity. The differential cross section as a function of the absolute value of the photon pseudorapidity is also presented in different regions of photon transverse energy. Next-to-leading-order QCD calculations from Jetphox and Sherpa as well as next-to-next-to-leading-order QCD calculations from Nnlojet are compared with the measurement, using several parameterisations of the proton parton distribution functions. The predictions provide a good description of the data within the experimental and theoretical uncertainties. [Figure not available: see fulltext.
Search for dark matter produced in association with bottom or top quarks in √s = 13 TeV pp collisions with the ATLAS detector
- Author
- Aaboud Morad
- Aad Georges
- Abbott Brad
- Abdinov Ovsat
- Abeloos Baptiste
- Abidi Syed
- AbouZeid Ossama
- Abraham Nicola
- Abramowicz Halina
- Abreu Henso
- Abreu Ricardo
- Abulaiti Yiming
- Acharya Bobby
- Adachi Shunsuke
- Adamczyk Leszek
- Adelman Jahred
- Adersberger Michael
- Adye Tim
- Affolder Tony
- Afik Yoav
- Agatonovic-Jovin Tatjana
- Agheorghiesei Catalin
- Aguilar-Saavedra Juan
- Ahlen Steven
- Ahmadov Faig
- Aielli Giulio
- Akatsuka Shunichi
- Akerstedt Henrik
- Akilli Ece
- Akimov Andrei
- Alberghi Gian
- Albert Justin
- Albicocco Pietro
- Alconada Verzini Maria
- Alderweireldt Sara
- Aleksa Martin
- Aleksandrov Igor
- Alexa Calin
- Alexander Gideon
- Alexopoulos Theodoros
- Alhroob Muhammad
- Ali Babar
- Aliev Malik
- Alimonti Gianluca
- Alison John
- Alkire Steven
- Allbrooke Benedict
- Allen Benjamin
- Allport Phillip
- Aloisio Alberto
- Alonso Alejandro
- Alonso Francisco
- Alpigiani Cristiano
- Alshehri Azzah
- Alstaty Mahmoud
- Alvarez Gonzalez Barbara
- Alviggi Mariagrazia
- Amadio Brian
- Amaral Coutinho Yara
- Amelung Christoph
- Amidei Dante
- Amor Dos Santos Susana
- Amoroso Simone
- Anastopoulos Christos
- Ancu Lucian
- Andari Nansi
- Andeen Timothy
- Anders Christoph
- Anders John
- Anderson Kelby
- Andreazza Attilio
- Andrei George
- Angelidakis Stylianos
- Angelozzi Ivan
- Angerami Aaron
- Anisenkov Alexey
- Anjos Nuno
- Annovi Alberto
- Antel Claire
- Antonelli Mario
- Antonov Alexey
- Antrim Daniel
- Anulli Fabio
- Aoki Masato
- Aperio Bella Ludovica
- Arabidze Giorgi
- Arai Yasuo
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- Araujo Ferraz Victor
- Arce Ayana
- Ardell Rose
- Arduh Francisco
- Arguin Jean-Francois
- Argyropoulos Spyridon
- Arik Metin
- Armbruster Aaron
- Armitage Lewis
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- Yoshihara Keisuke
- Young Charles
- Young Christopher
- Yu Jaehoon
- Yu Jie
- Yuen Stephanie
- Yusuff Imran
- Zabinski Bartlomiej
- Zacharis Georgios
- Zaidan Remi
- Zaitsev Alexander
- Zakharchuk Nataliia
- Zalieckas Justas
- Zaman Aungshuman
- Zambito Stefano
- Zanzi Daniele
- Zeitnitz Christian
- Zemaityte Gabija
- Zemla Andrzej
- Zeng Jian
- Zeng Qi
- Zenin Oleg
- Zerwas Dirk
- Zhang Dengfeng
- Zhang Dongliang
- Zhang Fangzhou
- Zhang Guangyi
- Zhang Huijun
- Zhang Jinlong
- Zhang Lei
- Zhang Liqing
- Zhang Matt
- Zhang Peng
- Zhang Rui
- Zhang Ruiqi
- Zhang Xueyao
- Zhang Yu
- Zhang Zhiqing
- Zhao Xiandong
- Zhao Yongke
- Zhao Zhengguo
- Zhemchugov Alexey
- Zhou Bing
- Zhou Chen
- Zhou Li
- Zhou Maosen
- Zhou Mingliang
- Zhou Ning
- Zhou You
- Zhu Cheng
- Zhu Hongbo
- Zhu Junjie
- Zhu Yingchun
- Zhuang Xuai
- Zhukov Konstantin
- Zibell Andre
- Zieminska Daria
- Zimine Nikolai
- Zimmermann Christoph
- Zimmermann Stephanie
- Zinonos Zinonas
- Zinser Markus
- Ziolkowski Michael
- Zobernig Georg
- Zoccoli Antonio
- Zou Rui
- zur Nedden Martin
- Zwalinski Lukasz
- Åkesson Torsten
- Šfiligoj Tina
- Ženiš Tibor
- Živković Lidija
- Άlvarez Piqueras Damián
- Publication venue
- 'Springer Science and Business Media LLC'
- Publication date
- 01/01/2017
- Field of study
A search for weakly interacting massive particle dark matter produced in association with bottom or top quarks is presented. Final states containing third-generation quarks and miss- ing transverse momentum are considered. The analysis uses 36.1 fb−1 of proton–proton collision data recorded by the ATLAS experiment at √s = 13 TeV in 2015 and 2016. No significant excess of events above the estimated backgrounds is observed. The results are in- terpreted in the framework of simplified models of spin-0 dark-matter mediators. For colour- neutral spin-0 mediators produced in association with top quarks and decaying into a pair of dark-matter particles, mediator masses below 50 GeV are excluded assuming a dark-matter candidate mass of 1 GeV and unitary couplings. For scalar and pseudoscalar mediators produced in association with bottom quarks, the search sets limits on the production cross- section of 300 times the predicted rate for mediators with masses between 10 and 50 GeV and assuming a dark-matter mass of 1 GeV and unitary coupling. Constraints on colour- charged scalar simplified models are also presented. Assuming a dark-matter particle mass of 35 GeV, mediator particles with mass below 1.1 TeV are excluded for couplings yielding a dark-matter relic density consistent with measurements
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- Author
- Abbass Hakam
- Adhikari Neill
- Affleck Julia
- Agno Sathianathan Ronan
- Ahmad Norfaizan
- Ahmed Iram
- Ainscough Kate
- Al Qasim Eman
- Al Swaidan Lolowa
- Al-Bassam Wisam
- Al-Beidh Farah
- Al-Beidh Farah
- Albert Martin
- Alegria Ana
- Alexander Brian
- Alexander Peter
- Allan Angela
- Allan Elizabeth
- Allen Louise
- Allibone Suzanne
- Amaro dos Santos Catorze Teodoro
- Anderson Tom
- Andric Zdravko
- Angus Derek
- Angus Derek C
- Anjum Aisha
- Ankert Juliane
- Annane Djillali
- Annane Djillali
- Anstey Matthew
- Antcliffe David
- Aparicio Christelle
- Appelt Peter
- Arabi Yaseen
- Arabi Yaseen
- Arbane Gill
- Archer Simon
- Aref Noah
- Arias Ana-Marie
- Arishi Hatim
- Arnold Donald
- Asghar Adeeba
- Ashelford Angela
- Attwood Ben
- Austin Karen
- Aysel Florescu Simin
- Azaiz Amine
- Babel Jakša
- Babio-Galan Maite
- Badie Julio
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- Baillie Kenneth
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- Bakthavatsalam Dhanalakshmi
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- Worner Ruth
- Wren Jess
- Wren Lynn
- Wrey Brown Caroline
- Writing Committee for the REMAP-CAP Investigators
- Xavier Kugan
- Xia Le Tai Charlotte
- Yarad Elizabeth
- Yates David
- Young Chelsea
- Young Ian
- Young Meredith
- Young Paul
- Yusuff Hakeem
- Zaharia Miahela Florentina
- Zaidi Abbas
- Zaki Ahmed
- Zaman Mohsin
- Zammit Claire
- Zapalac Marija
- Zarychanski Ryan
- Zarychanski Ryan
- Zhao Xiao Bei
- Zinzoni Vanessa
- Zitter Letizia
- Đimoti Renata
- Publication venue
- JAMA: Journal of the American Medical Association
- Publication date
- 06/10/2020
- Field of study
Importance: Evidence regarding corticosteroid use for severe coronavirus disease 2019 (COVID-19) is limited. Objective: To determine whether hydrocortisone improves outcome for patients with severe COVID-19. Design, Setting, and Participants: An ongoing adaptive platform trial testing multiple interventions within multiple therapeutic domains, for example, antiviral agents, corticosteroids, or immunoglobulin. Between March 9 and June 17, 2020, 614 adult patients with suspected or confirmed COVID-19 were enrolled and randomized within at least 1 domain following admission to an intensive care unit (ICU) for respiratory or cardiovascular organ support at 121 sites in 8 countries. Of these, 403 were randomized to open-label interventions within the corticosteroid domain. The domain was halted after results from another trial were released. Follow-up ended August 12, 2020. Interventions: The corticosteroid domain randomized participants to a fixed 7-day course of intravenous hydrocortisone (50 mg or 100 mg every 6 hours) (n = 143), a shock-dependent course (50 mg every 6 hours when shock was clinically evident) (n = 152), or no hydrocortisone (n = 108). Main Outcomes and Measures: The primary end point was organ support-free days (days alive and free of ICU-based respiratory or cardiovascular support) within 21 days, where patients who died were assigned -1 day. The primary analysis was a bayesian cumulative logistic model that included all patients enrolled with severe COVID-19, adjusting for age, sex, site, region, time, assignment to interventions within other domains, and domain and intervention eligibility. Superiority was defined as the posterior probability of an odds ratio greater than 1 (threshold for trial conclusion of superiority >99%). Results: After excluding 19 participants who withdrew consent, there were 384 patients (mean age, 60 years; 29% female) randomized to the fixed-dose (n = 137), shock-dependent (n = 146), and no (n = 101) hydrocortisone groups; 379 (99%) completed the study and were included in the analysis. The mean age for the 3 groups ranged between 59.5 and 60.4 years; most patients were male (range, 70.6%-71.5%); mean body mass index ranged between 29.7 and 30.9; and patients receiving mechanical ventilation ranged between 50.0% and 63.5%. For the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively, the median organ support-free days were 0 (IQR, -1 to 15), 0 (IQR, -1 to 13), and 0 (-1 to 11) days (composed of 30%, 26%, and 33% mortality rates and 11.5, 9.5, and 6 median organ support-free days among survivors). The median adjusted odds ratio and bayesian probability of superiority were 1.43 (95% credible interval, 0.91-2.27) and 93% for fixed-dose hydrocortisone, respectively, and were 1.22 (95% credible interval, 0.76-1.94) and 80% for shock-dependent hydrocortisone compared with no hydrocortisone. Serious adverse events were reported in 4 (3%), 5 (3%), and 1 (1%) patients in the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively. Conclusions and Relevance: Among patients with severe COVID-19, treatment with a 7-day fixed-dose course of hydrocortisone or shock-dependent dosing of hydrocortisone, compared with no hydrocortisone, resulted in 93% and 80% probabilities of superiority with regard to the odds of improvement in organ support-free days within 21 days. However, the trial was stopped early and no treatment strategy met prespecified criteria for statistical superiority, precluding definitive conclusions. Trial Registration: ClinicalTrials.gov Identifier: NCT02735707
Dimethyl fumarate in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial
- Author
- Abbas M.
- Abdul Rasheed A.
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- Field of study
Dimethyl fumarate (DMF) inhibits inflammasome-mediated inflammation and has been proposed as a treatment for patients hospitalised with COVID-19. This randomised, controlled, open-label platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing multiple treatments in patients hospitalised for COVID-19 (NCT04381936, ISRCTN50189673). In this assessment of DMF performed at 27 UK hospitals, adults were randomly allocated (1:1) to either usual standard of care alone or usual standard of care plus DMF. The primary outcome was clinical status on day 5 measured on a seven-point ordinal scale. Secondary outcomes were time to sustained improvement in clinical status, time to discharge, day 5 peripheral blood oxygenation, day 5 C-reactive protein, and improvement in day 10 clinical status. Between 2 March 2021 and 18 November 2021, 713 patients were enroled in the DMF evaluation, of whom 356 were randomly allocated to receive usual care plus DMF, and 357 to usual care alone. 95% of patients received corticosteroids as part of routine care. There was no evidence of a beneficial effect of DMF on clinical status at day 5 (common odds ratio of unfavourable outcome 1.12; 95% CI 0.86-1.47; p = 0.40). There was no significant effect of DMF on any secondary outcome
SARS-CoV-2 Omicron is an immune escape variant with an altered cell entry pathway
- Author
- Aanensen David M.
- Abraham Priyanka
- Abudahab Khalil
- Adams Alexander
- Adams Helen
- Adele Sandra
- Afifi Safiah
- Aggarwal Dinesh
- Ahmad Shazaad S. Y.
- Aigrain Louise
- Alcolea-Medina Adela
- Alikhan Nabil-Fareed
- Allara Elias
- Amato Roberto
- Angyal Adrienn
- Annett Tara
- Ansari M. Azim
- Aplin Stephen
- Ariani Cristina V.
- Asad Hibo
- Asamaphan Patawee
- Ash Amy
- Ashfield Paula
- Ashford Fiona
- Ashraf Shirin
- Atkinson Laura
- Attwood Stephen W.
- Auckland Cressida
- Austin James
- Aydin Alp
- Baker David J.
- Baker Paul
- Balcazar Carlos E.
- Ball Jonathan
- Barnes Eleanor
- Barrett Jeffrey C.
- Barrow Magdalena
- Barton Edward
- Bashton Matthew
- Bassett Andrew R.
- Batra Rahul
- Baxter Chris
- Bayzid Nadua
- Beaver Charlotte
- Beckett Angela H.
- Beckwith Shaun M.
- Bedford Luke
- Beer Robert
- Beggs Andrew
- Bellis Katherine L.
- Berry Louise
- Bertolusso Beatrice
- Best Angus
- Betteridge Emma
- Bibby David
- Bicknell Kelly
- Binns Debbie
- Birchley Alec
- Bird Paul W.
- Bishop Chloe
- Blacow Rachel
- Blakey Victoria
- Blane Beth
- Bolt Frances
- Bonfield James
- Bonner Stephen
- Bonsall David
- Boswell Tim
- Bosworth Andrew
- Bourgeois Yann
- Bouzidi Kate El
- Boyd Olivia
- Bradley Declan T.
- Breen Cassie
- Bresner Catherine
- Breuer Judith
- Bridgett Stephen
- Bronner Iraad F.
- Brooks Ellena
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- Brown Anthony
- Brown Julianne R.
- Bucca Giselda
- Buchan Sarah L.
- Buck David
- Bull Matthew
- Burns Phillipa J.
- Burton-Fanning Shirelle
- Byaruhanga Timothy
- Byott Matthew
- Campbell Sharon
- Cantoni Diego
- Carabelli Alessandro M.
- Cargill James S.
- Carlile Matthew
- Carvalho Sílvia F.
- Casey Anna
- Castigador Anibolina
- Catalan Jana
- Chalker Vicki
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- Zarebski Alex E.
- Zhang Peijun
- Publication venue
- 'Springer Science and Business Media LLC'
- Publication date
- 31/08/2022
- Field of study
Vaccines based on the spike protein of SARS-CoV-2 are a cornerstone of the public health response to COVID-19. The emergence of hypermutated, increasingly transmissible variants of concern (VOCs) threaten this strategy. Omicron (B.1.1.529), the fifth VOC to be described, harbours multiple amino acid mutations in spike, half of which lie within the receptor-binding domain. Here we demonstrate substantial evasion of neutralization by Omicron BA.1 and BA.2 variants in vitro using sera from individuals vaccinated with ChAdOx1, BNT162b2 and mRNA-1273. These data were mirrored by a substantial reduction in real-world vaccine effectiveness that was partially restored by booster vaccination. The Omicron variants BA.1 and BA.2 did not induce cell syncytia in vitro and favoured a TMPRSS2-independent endosomal entry pathway, these phenotypes mapping to distinct regions of the spike protein. Impaired cell fusion was determined by the receptor-binding domain, while endosomal entry mapped to the S2 domain. Such marked changes in antigenicity and replicative biology may underlie the rapid global spread and altered pathogenicity of the Omicron variant
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