25 research outputs found
SLUGBOT, an Aplysia-inspired Robotic Grasper for Studying Control
- Author
- Publication venue
- Publication date
- 21/11/2022
- Field of study
Living systems can use a single periphery to perform a variety of tasks and
adapt to a dynamic environment. This multifunctionality is achieved through the
use of neural circuitry that adaptively controls the reconfigurable
musculature. Current robotic systems struggle to flexibly adapt to unstructured
environments. Through mimicry of the neuromechanical coupling seen in living
organisms, robotic systems could potentially achieve greater autonomy. The
tractable neuromechanics of the sea slug Aplysia californicaâs
feeding apparatus, or buccal mass, make it an ideal candidate for applying
neuromechanical principles to the control of a soft robot. In this work, a
robotic grasper was designed to mimic specific morphology of the
Aplysia feeding apparatus. These include the use of soft actuators
akin to biological muscle, a deformable grasping surface, and a similar
muscular architecture. A previously developed Boolean neural controller was
then adapted for the control of this soft robotic system. The robot was capable
of qualitatively replicating swallowing behavior by cyclically ingesting a
plastic tube. The robot's normalized translational and rotational kinematics of
the odontophore followed profiles observed in vivo despite
morphological differences. This brings Aplysia-inspired control
in roboto one step closer to multifunctional neural control schema
in vivo and in silico. Future additions may improve
SLUGBOT's viability as a neuromechanical research platform.Comment: Submitted and accepted to Living Machines 2022 conferenc
Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial
- Author
- Abano Nenette
- Abbdul-saheb Mudhar
- Adedoyin Temi
- Adell Victoria
- Adesina Tolu
- Adie Katja
- Adil-Smith Jennifer
- Ahmad Nasar
- Ahmed Ashraf
- Ahmed Iman
- Al-Mayhani Talal
- Al-Shahi Salman Rustam
- Al-Shahi Salman Rustam
- Alam Mohammad Irfan
- Albazzaz Mo
- Ali Ali
- Alipio Francis
- Allen Christopher
- Allison Joanna
- Amey Isobel
- Amis Elaine
- Amlani Sageet
- Amoils Shannon
- Amor Kelly
- Anderson Rosemary
- Andole Sreeman
- Anjum Talat
- Ankolekar Sandeep
- Annamalai Arunkumar
- Anthony Alpha
- Anversha Ajmal
- Anwar Ijaz
- Anwar Sajjad
- Appleton Jason
- Argandona Lucia
- Armitage Jane
- Ashton Amy
- Atkinson Natalie
- Auld Grace
- Avis Joanne
- Aweid Basaam
- Ayres Georgina
- Azhar Khalid
- Bagnall Caroline
- Baig Farrukh
- Baigent Colin
- Bailey Duncan
- Baird Yolanda
- Bakawala Rehana
- Baker John
- Baker Pauline
- Balazikova Olga
- Balian Linda
- Baliga Vidya
- Balitska Olesia
- Ball Julie
- Ball Margaret
- Ballantine Robert
- Bamford John
- Banaras Azra
- Barber Mark
- Barbon Emma
- Barker James
- Barr Charlotte
- Barrie Elizabeth
- Barron Luke
- Barry Adrian
- Bateman Gavin
- Bates Michelle
- Bathula Rajaram
- Battersby-Wood Emma
- Bayliss Pauline
- Beadle Hannah
- Bearne Helen
- Beaty Teresa
- Beaves Emily
- Bell Angela
- Bell Jo
- Bell Murdina
- Bellfield Ruth
- Beranova Eva
- Bergin Adrian
- Bhakri Harbens
- Bhalla Ajay
- Bharaj Kiranjit
- Bhargava Maneesh
- Bhaskaran Biju
- Bhatnagar Priya
- Bhatnagar Priya
- Birchall Kathryn
- Birns Jonathan
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- Blair Caroline
- Blair Caroline
- Blair Gordon
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- Blank Catrin
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- Chandrakumar Aberami
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- Chapman Nicola
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- Chatterjee Kausic
- Chaudhry Afnan
- Chauhan Meena
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- Dennis Martin S
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- Doherty Mandy
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- Drever Jonathan
- du Plessis Johann C
- du Plessis Johannes
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- Eglinton Charlotte
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- Esson Derek
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- Finlay Sarah
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- Fitzell Pauline
- Fitzsimmons Paul
- Fletcher Glyn
- Fletcher Jo
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- Foote Leanne
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- Foster Eliza
- Fotherby Ken
- Fox Charlotte
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- Gadapa Naveen
- Gainard Glyn
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- Hedstrom Amanda
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- Iqbal Mohammad Shazad
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- Jackson Linda
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- James Claire
- James Martin
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- Jeyaraj Naomi
- Jha Ratneshwari
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- Jose Deepa
- Jose Josin
- Joshi Yogish
- Joshi Yogish
- Joyson Anu
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- Justin Frances
- Kakar Puneet
- Kalathil Latheef
- Kalladka Dheeraj
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- Krishnamoorthy Shrivakumar
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- Kumar Balakrishna
- Kumar Pradeep
- Kunhunny Swapna
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- Langhorne Peter
- Lasserson Daniel
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- Lerpiniere Christine
- Licenik Radim
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- Loganathan Thayalini
- Longland Barbara
- Lopez Paula
- Lovelock Caroline
- Lowe Gordon
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- Lucas Suzanne
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- Maatouk Ahmad
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- MacInnes Brian
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- MacLiver Linda
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- Manoj Aravind
- Mardania Rina
- Marigold James Richard
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- Marks Katherine
- Marsden Tracy
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- Martin Irene
- Mashate Sheila
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- Mate Abhijit
- Mathieson Philip
- Matias Oliver
- Matthews Christopher
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- McArdle Damian
- Mcauley Sean
- McCann Stephanie
- McCarron Mark
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- McCormick Katrina
- McCormick Katrina
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- McDonald Susan
- Mcgee Joanne
- McGhee Caroline
- McGill Connor
- McGrath Aileen
- McIlmoyle James
- McKee Jacqueline
- McLoughlin Alison
- McVerry Ferghal
- Mead Denise
- Mead Gillian
- Meir Julie
- Menon Nisha
- Mercer Lily
- Metcalf Kneale
- Miller Keniesha
- Miller Richard
- Milligan Josette
- Minks David
- Minks David P.
- Miriam Skelton
- Mistri Amit
- Mitchell Jennifer
- Mitra Dipayan
- Mitra Dipayan
- Mohammed Niaz
- Mohd Nor Azlisham
- Mokoena Betty
- Moores Andrew
- Moqsith Mohammed
- Morell Jordi
- Moreton Fiona
- Morgan Debbie
- Moroney Helen
- Morse Bethan
- Moseley Sally
- Motherwell Nichola
- Moynihan Barry
- Mpelembue Mushiya
- Mudd Paul
- Muddegowda Girish
- Muir Keith
- Mukherjee Indranil
- Murali Elodie
- Murphy Peter
- Murray Gordon D
- Musarrat Kashif
- Myint Min
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- Naing Zin
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- Nallasivan Arumugam
- Nasar Mohammad
- Nasim Ashraf
- Naylor Charde
- Needle Ann
- Nelson Sandra
- Newby David E
- Newton Sophie
- Ng Kheng Xiong
- Ngo David
- Nguyen Vinh
- Ngwako Mmua
- Ni Hlaing
- Nicholas Paul
- Nicolson Anne
- Niranchanan Rangah
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- Njoku Kelechi
- Nott Claire
- Nott Claire
- Nozedar Tarn
- Nyabadza Sheila
- O'Brien Eoin
- O'Brien Richard
- O'Brien Richard
- O'Connell Susan
- O'Loughlin Victoria
- O'Reilly Joanna
- O'Toole Sarah
- OConnell Janice
- Oji Nnebuife
- Orath Prabakaran Rajalakshmi
- Orefo Chukwuka
- Orugun Enoch
- Osborn Mairead
- Osborne Emily
- Oshodi Anne
- Osman Ahmed
- Ovington Catherine
- Owings Paula
- Owoyele Emmanuelle
- Owusu-Agyei Peter
- Pai Yogish
- Palmer Jeb
- Papavasileiou Vasileios
- Parakramawansha Ruwan
- Parker Richard
- Parry Anthea
- Parry-Jones Adrian
- Pasco Kath
- Patel Bhavini
- Patel Champa
- Patel Farzana
- Patel Krishna
- Patterson Chris
- Paulton Ruth
- Pawley Corinne
- Peixoto Cassilda
- Penge Justin
- Perez Jane
- Perfitt Rebekah
- Perkins Charlotte
- Perry David
- Perry Jack
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- Pettitt Kerry
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- Pitt-Kerby Tressy
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- Proeschel Harald
- Punekar Shuja
- Punter Martin
- Pusalkar Aparna
- Putterill Janet
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- Quinn Outi
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- Raghunathan Senthil
- Rahman Bithi
- Rai Baljinder
- Raj Sonia
- Rajapakse Anoja
- Rajkumar Chakravarthi
- Ramachandran Sankaranarayana
- Ramadan Hawraman
- Ramshaw Alex
- Rana Pratap
- Randall Marc
- Rashed Khalid
- Rashmi Sindhu
- Ravenhill Garth
- Rayessa Rayessa
- Reckless Ian
- Reddan Julie
- Reddan Julie
- Redgrave Jessica
- Redjep Ozlem
- Remegoso Alda
- Richard Bella
- Richards Emma
- Rinkel Gabriel
- Roberts Josh
- Robinson Matthew
- Robinson Naomi
- Rodgers Alicia
- Rodrigues Mark A
- Rodriguez Aryelly
- Roffe Christine
- Roffe Jack
- Roganova Tatjana
- Rogers Emily
- Rogers Gill
- Rojas Javier
- Ross Sarah
- Roughan Caroline
- Rudd Tony
- Rudenko Hannah
- Saada Janak
- Saastamoinen Kari
- Sajid Mahmud
- Sakka Eleni
- Salehin Maqsud
- Salek-Haddadi Afraim
- Salih Isam
- Sally Moore
- Sandercock Peter A G
- Sangombe Mirriam
- Sangster Graeme
- Sanyal Ranjan
- Sarah Procter
- Sarah Procter
- Sattar Naweed
- Sattar Saira
- Saulat Afaq
- Saulat Afaq
- Schofield Christine
- Schulz Ursula
- Schumacher Natasha
- Schwarz Stefan
- Seagrave Samantha
- Sekaran Lakshmanan
- Sesay Juliana
- Sethuraman Sakthivel
- Shackcloth Daniela
- Shah Alex
- Shah Sweni
- Shahmehri Shahrzad
- Sharma Nikhil
- Sharpe Simon
- Shaw Kelly Marie
- Shaw Louise
- Sheikh Saima
- Shekhar Raj
- Shelton Faye
- Shinh Naval
- Shread Ian
- Shukla Avani
- Siddegowda Prasad
- Siddiq Muhammad
- Siddiqui Amber
- Siddiqui Anwer
- Sigsworth Andrew
- Simon Rohan
- Sims Don
- Singh Arun
- Sinha Devesh
- Skinner Helen
- Slade Peter
- Smart Amanda
- Smith Andrew
- Smith Fiona
- Smith Gemma Marie
- Smith Simon
- Smith Wilma
- Smyth Nigel
- Spencer Jayne
- Sprigg Nikola
- Sprigg Nikola
- Srinivasan Meena
- Stafford Samantha
- Stafford Samantha
- Stanners Andrew
- Steele Amy
- Stephen Jacqueline
- Stephens Claire
- Stevens Angela
- Stevens Stephanie
- Stevenson Sarah
- Stewart Kelvin
- Stocks Kathy
- Stone Andrew
- Storton Sharon
- Strain David
- Subramonian Santhosh
- Sudlow Cathie
- Sudlow Cathie L M
- Sukdeo Varthi
- Sullivan Frank
- Sultan Sulaiman
- Suttling Anne
- Sutton Claire
- Sutton Patrick
- Sutton Victoria
- Sword Jane
- Sykes Lucy
- Symonds Stuart
- Szabo Susan
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- Tandy Jane
- Tate Margaret
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- Tayler Michelle
- Taylor Pat
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- Temple Natalie
- Thant Hlaing
- Thavanesan Kamy
- Thomas Isobel
- Thomas Kelly
- Thomas Philip
- Thomas Sarah
- Thompson Philip
- Thompson Susan
- Thompson Teresa
- Thompson-Jones Helen
- Thomson Audrey
- Thornthwaite Sarah
- Thorpe Kevin
- Tilley Victoria
- Tiwari Divya
- Tomlin Dawn
- Tomlinson Benjamin
- Treadwell Shelley
- Tribbeck Michele
- Trippier Sarah
- Triscott Claire
- Triscott Claire
- Tryambake Dinesh
- Tucker Laura
- Tucker Susan
- Turfrey Jennifer
- Tysoe Sharon
- Ullah Khalil
- Valentine Stacey
- van Someren Chloe
- Varquez Resti
- Vasileiadis Evangelos
- Vassallo Joseph
- Venter Marius
- Veraque Emelda
- Verrion Anna
- Vettimootal Johnson Venetia
- Vickers Carinna
- Walford Jamie
- Walker Allan
- Walker Marion
- Walker Pauli
- Walker Susannah
- Wallace Aine
- Wallace Rebecca
- Wallace Rebecca
- Walstow Deborah
- Walter Deborah
- Walters Ashleigh
- Wani Mushtaq
- Ward Deborah
- Wardlaw Joanna M
- Watchurst Caroline
- Waterfield Kelly
- Waterfield Kelly
- Watson Fran
- Waugh Dean
- Webb Tom
- Webber Adam
- Webster Timothy
- Weinling Marie
- Weir Nic
- Weir Pauline
- Welch Angela
- Werring David
- Werring David J
- Whitcher Alison
- White James
- White Julie
- White Philip M
- White Susan
- Whiteley William
- Whiteley William N
- Whiteman Jessica
- Whiteman Jessica
- Whiting Robert
- Whittamore Katherine
- Wiggam Ivan
- Wilding Peter
- Wilkes Gwendoline
- Wilkinson Mark
- Willberry Angela
- Williams Carol
- Williams Rebecca
- Williams-Yesson Barbara
- Willmot Mark
- Wilson David
- Wilson Duncan
- Wilson Jenny
- Wilson Lisa
- Wilson Sarah
- Wiltshire Alison
- Wood Diane
- Wood Edith
- Wood Lisa
- Woodward Stephen
- Wright Fiona
- Wroath Belinda
- Wynter Inez
- Yadava Rajendra
- Yip Brigitte
- Young Andrew
- Zachariah George
- Zahoor Tajammal
- Zoe Mellor
- Publication venue
- 'Elsevier BV'
- Publication date
- 22/05/2019
- Field of study
Background
Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy
Pre-Clinical Evaluation of a Replication-Competent Recombinant Adenovirus Serotype 4 Vaccine Expressing Influenza H5 Hemagglutinin
- Author
- A Lyons
- A Narang
- AE Kajon
- Ben Guenther
- CA Gaydos
- CO Tacket
- CS Rollier
- DA Muruve
- Darly J. Manayani
- DH Barouch
- DH Holman
- DJ Alexander
- EE Thacker
- ES Gabitzsch
- FA Pedreira
- Fermin Garduno
- FH Top Jr
- G Neumann
- Glenn Ishioka
- H Kaneko
- IM Belyakov
- J Steitz
- J Wang
- J Zhu
- JA Belser
- Jason Mendy
- Jeff Alexander
- Jenny B. Avanzini
- JM Wood
- JS Richardson
- K Lore
- KH Hsu
- KJ Limbach
- KM Butt
- KS Park
- Lily Jow
- Lj Reed
- Lo Vang
- M Aaman
- M Robert-Guroff
- M Santosuosso
- MA Croyle
- MA Hoelscher
- MA Hoelscher
- Mark J. Newman
- MB Appaiahgari
- MD Lubeck
- MJ Gurwith
- MK Knowles
- MR Soboleski
- MT Arevalo
- MV Chengalvala
- Peggy Farness
- PR Johnson Jr
- PW Roelvink
- PW Shabram
- R Alcock
- R Vita
- RB Couch
- RG Webster
- RJ Cox
- S Dubey
- S Khanam
- Simone Ward
- SL Ludwig
- SN Tucker
- Stephen Mark Tompkins
- Tim Mayall
- V Cerullo
- VA Fulginiti
- Victoria Snarsky
- W Gao
- X Huang
- Xin Dong
- ZC Hartman
- ZQ Xiang
- Publication venue
- Public Library of Science
- Publication date
- 17/02/2012
- Field of study
Influenza virus remains a significant health and social concern in part because of newly emerging strains, such as avian H5N1 virus. We have developed a prototype H5N1 vaccine using a recombinant, replication-competent Adenovirus serotype 4 (Ad4) vector, derived from the U.S. military Ad4 vaccine strain, to express the hemagglutinin (HA) gene from A/Vietnam/1194/2004 influenza virus (Ad4-H5-Vtn). Our hypothesis is that a mucosally-delivered replicating Ad4-H5-Vtn recombinant vector will be safe and induce protective immunity against H5N1 influenza virus infection and disease pathogenesis.The Ad4-H5-Vtn vaccine was designed with a partial deletion of the E3 region of Ad4 to accommodate the influenza HA gene. Replication and growth kinetics of the vaccine virus in multiple human cell lines indicated that the vaccine virus is attenuated relative to the wild type virus. Expression of the HA transgene in infected cells was documented by flow cytometry, western blot analysis and induction of HA-specific antibody and cellular immune responses in mice. Of particular note, mice immunized intranasally with the Ad4-H5-Vtn vaccine were protected against lethal H5N1 reassortant viral challenge even in the presence of pre-existing immunity to the Ad4 wild type virus.Several non-clinical attributes of this vaccine including safety, induction of HA-specific humoral and cellular immunity, and efficacy were demonstrated using an animal model to support Phase 1 clinical trial evaluation of this new vaccine
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
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- S Whiteley
- S Williams
- S Wood
- S Yussuf
- Sabino Scolletta
- Samreen Ijaz
- Sandro Mancarella
- Sandro Panese
- Sara Amitrano
- Sara McDonald
- Sarah Law
- Sarah McCafferty
- Saverio Giuseppe Parisi
- Saye Khoo
- Scott Richard
- Semple Malcolm G
- Serafina Valente
- Serena Ludovisi
- Sergio Daga
- SeĂĄn Keating
- Shankar-Hari Manu
- Shen Xia
- Shih Barbara
- Shiranee Sriskandan
- Shona C Moore
- Silvia Cappelli
- Simona Marcantonio
- Simone Furini
- Sophie Halpin
- Sophie Venturelli
- Stefania Mantovani
- Stefano Baratti
- Stefano Ceri
- Stefano Rusconi
- Stella Aslibekyan
- Stephanie Roberts
- Stephen R Knight
- Summers Charlotte
- Susanna Croci
- Susanna Guerrini
- T Anderson
- T Arden
- T Baird
- T Behan
- T Bemand
- T Cosier
- T Coventry
- T Duncan
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- T Kannan
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- T McHugh
- T Newman
- T Nortcliffe
- T O Jones
- T Pogreban
- T Rees
- T Samakomva
- T Smith
- T Smith
- T Szakmany
- T Varghes
- T Williams
- 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
- V Page
- V Parris
- V Parris
- V Pristopan
- V Ratnam
- V Rivers
- V Sarathy
- V Thomas
- V Thwaites
- 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
Dimethyl fumarate in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial
- Author
- Abbas M.
- Abdul Rasheed A.
- Abdul A.
- Abdul-Kadir R.
- Abdusamad K.
- Abernethy K.
- Aboelela H.
- Abouzaid M.
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- Zhu D.
- Zia M.
- Zitter L.
- Zuhra N.
- Zullo C.
- Publication venue
- Springer Science and Business Media LLC
- Publication date
- 31/01/2024
- 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; pâ=â0.40). There was no significant effect of DMF on any secondary outcome
Multiorgan MRI findings after hospitalisation with COVID-19 in the UK (C-MORE): a prospective, multicentre, observational cohort study
- Author
- Abel K
- Adamali H.
- Adeloye D
- Adeyemi Oluwaseun
- Adrego Rita
- Aguilar Jimenez Laura A.
- Ahmad Haider N
- Ahmad Shanaz
- Ahmed R
- Ahwireng Nyarko
- Ainsworth Mark
- Al-Sheklly B.
- Alamoudi Asma
- Alfaro-Almagro Fidel
- Ali Mariam
- Aljaroof M
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- Allen R J
- Allerton Lisa
- Allsop Lynne
- Allt Ann Marie
- Almeida Paula
- Altmann Danny
- Alvarez Corral Maria
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- Arbane Gill
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- Zongo O.
- Publication venue
- Elsevier
- Publication date
- 22/09/2023
- Field of study
Introduction:
The multiorgan impact of moderate to severe coronavirus infections in the post-acute phase is still poorly understood. We aimed to evaluate the excess burden of multiorgan abnormalities after hospitalisation with COVID-19, evaluate their determinants, and explore associations with patient-related outcome measures.
Methods:
In a prospective, UK-wide, multicentre MRI follow-up study (C-MORE), adults (aged â„18 years) discharged from hospital following COVID-19 who were included in Tier 2 of the Post-hospitalisation COVID-19 study (PHOSP-COVID) and contemporary controls with no evidence of previous COVID-19 (SARS-CoV-2 nucleocapsid antibody negative) underwent multiorgan MRI (lungs, heart, brain, liver, and kidneys) with quantitative and qualitative assessment of images and clinical adjudication when relevant. Individuals with end-stage renal failure or contraindications to MRI were excluded. Participants also underwent detailed recording of symptoms, and physiological and biochemical tests. The primary outcome was the excess burden of multiorgan abnormalities (two or more organs) relative to controls, with further adjustments for potential confounders. The C-MORE study is ongoing and is registered with ClinicalTrials.gov, NCT04510025.
Findings:
Of 2710 participants in Tier 2 of PHOSP-COVID, 531 were recruited across 13 UK-wide C-MORE sites. After exclusions, 259 C-MORE patients (mean age 57 years [SD 12]; 158 [61%] male and 101 [39%] female) who were discharged from hospital with PCR-confirmed or clinically diagnosed COVID-19 between March 1, 2020, and Nov 1, 2021, and 52 non-COVID-19 controls from the community (mean age 49 years [SD 14]; 30 [58%] male and 22 [42%] female) were included in the analysis. Patients were assessed at a median of 5·0 months (IQR 4·2â6·3) after hospital discharge. Compared with non-COVID-19 controls, patients were older, living with more obesity, and had more comorbidities. Multiorgan abnormalities on MRI were more frequent in patients than in controls (157 [61%] of 259 vs 14 [27%] of 52; p<0·0001) and independently associated with COVID-19 status (odds ratio [OR] 2·9 [95% CI 1·5â5·8]; padjusted=0·0023) after adjusting for relevant confounders. Compared with controls, patients were more likely to have MRI evidence of lung abnormalities (p=0·0001; parenchymal abnormalities), brain abnormalities (p<0·0001; more white matter hyperintensities and regional brain volume reduction), and kidney abnormalities (p=0·014; lower medullary T1 and loss of corticomedullary differentiation), whereas cardiac and liver MRI abnormalities were similar between patients and controls. Patients with multiorgan abnormalities were older (difference in mean age 7 years [95% CI 4â10]; mean age of 59·8 years [SD 11·7] with multiorgan abnormalities vs mean age of 52·8 years [11·9] without multiorgan abnormalities; p<0·0001), more likely to have three or more comorbidities (OR 2·47 [1·32â4·82]; padjusted=0·0059), and more likely to have a more severe acute infection (acute CRP >5mg/L, OR 3·55 [1·23â11·88]; padjusted=0·025) than those without multiorgan abnormalities. Presence of lung MRI abnormalities was associated with a two-fold higher risk of chest tightness, and multiorgan MRI abnormalities were associated with severe and very severe persistent physical and mental health impairment (PHOSP-COVID symptom clusters) after hospitalisation.
Interpretation:
After hospitalisation for COVID-19, people are at risk of multiorgan abnormalities in the medium term. Our findings emphasise the need for proactive multidisciplinary care pathways, with the potential for imaging to guide surveillance frequency and therapeutic stratification
Dimethyl fumarate in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial
- Author
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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; pâ=â0.40). There was no significant effect of DMF on any secondary outcome
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
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- Bagshaw Sean
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- Baikady Ravishankar
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- Baker Stuart
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- 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
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- Bonten Marc J. M.
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- D?Amato Fabiola
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- Dawson Laura Ann
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- De Bus Liesbet
- de Courcy-Golder Kim
- de Groot Klaas
- de Jong Menno
- de Jonge Evert
- De Keulenaer Bart
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- del Sorbo Lorenzo
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- 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
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- Dyas Sarah
- Eapen Beena
- Eastgate Christine
- Ebenezer R
- Edmunds Natasha
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- Efford Georgia
- Egreteau Pierre
- Ehrmann Stephan
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- Eisenbeis Simone
- Ekhérian Jean-Michel
- El-Khawas Khaled
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- Estcourt Lise J.
- Estensen Kristen
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- Ferreira Ricardo Manuel Castro
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- Goddard Wendy
- Godement Mathieu
- Godoy Lucas C.
- Goebeler M.E.
- Golden David
- Goldman John
- Goligher Ewan
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- Gopinath Amitha
- Goralski Patricia
- Gordon Anthony C.
- Gosbell Iain
- Gould Richard
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- Göpel Siri
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- Haider Nafeesah
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- Hakak Sheeba
- Halden Sandra
- Haldeos Anne
- Hall Alistair S
- Hall Amelia
- Hall Andrew
- Hall Kathryn
- Hall Rebecca
- Hamilton David
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- Hamlyn Vincent
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- Harding Daniel
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- Harper Heather
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- Harris Celia
- Harris Jade
- Harris John
- Harrison David A.
- Harrison Susan
- Harrow Kath
- Hartley Melissa
- Harvala-Simmonds Heli
- Harvey Alice
- Harvey Daniel
- Harvey James
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- Haydon Tim
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- Headlam Evie
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- Hegazy Ahmed
- Hegazy Mohamed
- Heinonen Jonna
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- Heming Nicholas
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- Henderson Steven
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- Hensley Joseph
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- Hernandez Erik
- Hewitt Claire
- Hey Samuel
- Hickey John
- Hierons Sarah
- Higgins Alisa M.
- Hill Claire
- Hill Dianne
- Hill Helen
- Hilldrith Anette
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- Hin Lui Lok
- Hindle Grace
- Hinrichs Carl
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- Hodge Christopher
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- Hodgson Helen
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- Homes Jennifer
- Honda Hitoshi
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- Hopkins Phil
- Hormis Anil
- Horner Dan
- Hornsby James
- Horton Michelle
- Horvat Christopher M.
- Howcroft Clare
- Howell Alice
- Hower Martin
- Howie Lucy
- Howle Ryan
- Hoxha Elvira
- Huang David T.
- Hughes Debbie
- Hugill Keith
- Huijbens Danique
- Hullegie Sebastiaan
- Hulley Amanda
- Hulme Jonathan
- Hulse Sarah
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- Hunt Beverley
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- Hutton Paula
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- Irving Ben
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- Jacquier Sophie
- Jafarzadeh Mina
- Jagannathan Vijay
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- Jan Hassing Robert
- Janin Pierre
- Jarczak Dominik
- Jarman Claire
- Jayakumar Deva
- Jayakumar Devachandran
- Jean-Pierre Eraldi
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- Jenkins Samuel
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- Jenkins Steve
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- Jha Avinash
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- Jongebloed Katherine
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- Juhaz Vera
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- Kiiski Heikki
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- Kim Edy Y.
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- Kong Jing
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- Kosa Alma
- Kremling Julius
- KreĂ Gabriele
- Krishnamoorthy S
- Krishnamurthy Vinodh
- Kruger Peter
- Kruisdijk-Gerritsen Arriette
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- Labbe Vincent
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- Landsiedel-Mechenbier Elke
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- Laugs Fabian
- Lavana Jayshree
- Laver Russell D.
- Law Daniel
- Lawler Patrick R.
- Le Basnier Elliot
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- Leaf David E.
- Lean Richard
- Leaver Susannah
- Leavis Helen
- Leblond Julie
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- Lesona Eden
- Levett Chris
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- Lewis Roger J.
- Lewis Sarah
- LewisProsser Lorraine
- Liao Angela
- Lim Rosario
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- Linstrum Kelsey M.
- Litton Ed
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- Liu Theresa
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- McAdams David
- McArthur Colin J.
- McAuley Daniel F.
- McAuley Julie
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- McGoldrick Clare
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- McGuinness Shay P.
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- McKee Madeleine
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- Yamagishi Yoshiaki
- Yamashita Chizuru
- Yang Yang
- Yarad Elizabeth
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- Yates David
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- 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
Kinesin and Dynein Mechanics: Measurement Methods and Research Applications
- Publication venue
- 'ASME International'
- Publication date
- Field of study