28 research outputs found
The CDKL5 disorder is an independent clinical entity associated with early-onset encephalopathy
- Author
- A Bebbington
- A Erez
- A Jansen
- Alessandra Murgia
- C Cordova-Fletes
- C Nemos
- D Mei
- F Hanefield
- F Kortüm
- F Melani
- G Coppola
- G Marangi
- Gladys Ho
- H Leonard
- H Rosas-Vargas
- H Saitsu
- H Van Esch
- Helen Leonard
- HL Archer
- I Bertani
- I Scheffer
- J Masliah-Plachon
- J Nectoux
- J Tao
- JC Evans
- JE Allanson
- Jenny Downs
- JL Neul
- John Christodoulou
- JS Liang
- K Hadzsiev
- KM Klein
- LS Weaving
- M Bartnik
- M Castrén
- M Elia
- Marilena Vecchi
- Meredith Wilson
- N Bahi-Buisson
- N Bahi-Buisson
- N Bahi-Buisson
- N Rademacher
- Nick de Klerk
- P Kankirawatana
- R Artuso
- R White
- Roberta Polli
- S Fehr
- S Grosso
- S Psoni
- S Russo
- S Sartori
- Simon Williams
- Stavroula Psoni
- Stefano Sartori
- Stephanie Fehr
- T Sprovieri
- U Intusoma
- VM Kalscheuer
- WHO multicentre growth reference study group
- Xenia L. Stalpers
- Xinhua Bao
- Y Fichou
- Publication venue
- 'Springer Science and Business Media LLC'
- Publication date
- 01/01/2012
- Field of study
The clinical understanding of the CDKL5 disorder remains limited, with most information being derived from small patient groups seen at individual centres. This study uses a large international data collection to describe the clinical profile of the CDKL5 disorder and compare with Rett syndrome (RTT). Information on individuals with cyclin-dependent kinase-like 5 (CDKL5) mutations (n=86) and females with MECP2 mutations (n=920) was sourced from the InterRett database. Available photographs of CDKL5 patients were examined for dysmorphic features. The proportion of CDKL5 patients meeting the recent Neul criteria for atypical RTT was determined. Logistic regression and time-to-event analyses were used to compare the occurrence of Rett-like features in those with MECP2 and CDKL5 mutations. Most individuals with CDKL5 mutations had severe developmental delay from birth, seizure onset before the age of 3 months and similar non-dysmorphic features. Less than one-quarter met the criteria for early-onset seizure variant RTT. Seizures and sleep disturbances were more common than in those with MECP2 mutations whereas features of regression and spinal curvature were less common. The CDKL5 disorder presents with a distinct clinical profile and a subtle facial, limb and hand phenotype that may assist in differentiation from other early-onset encephalopathies. Although mutations in the CDKL5 gene have been described in association with the early-onset variant of RTT, in our study the majority did not meet these criteria. Therefore, the CDKL5 disorder should be considered separate to RTT, rather than another variant
Finishing the euchromatic sequence of the human genome
- Author
- . Haifeng
- . Magner
- . Yin
- Abbott Scott
- Abbott-Ozersky Amanda
- Abdellah Zahra
- Abouelleil Amr
- Abrajano Anne
- Adachi Tamami
- Adam Catherine
- Adams Charles Q.
- Adamson Aaron
- Adekoya Emmanuel
- Adio-Oduola Babajide
- Aerts Andrea
- Aggarwal Arun
- Ahmadi Alireza
- Ahmed Shahana
- Aimable Matthew
- Ainscough Rachael
- Ait-Zahra Mostafa
- Aizu Tomoyuki
- Alcivare Dana
- Alegria Michelle
- Ali Alla
- Ali Johar
- Allegria-hartmann Michelle
- Alleman Jennifer
- Allen Carlana C.
- Allen Heather
- Allen Nicole R.
- Allen Susan
- Allen Thaddeus
- Almeida Jeff
- Almond Claire
- Alsbrooks Stephen L.
- Altherr Michael R.
- Amaratunge Harshinie C.
- Ambler Andrew
- Ambrose Karen
- Ambrose Kerrie
- Amemiya Chris
- Amico-Keller Gina
- Amin Amita G.
- Anderson Mechele
- Anderson Scott
- Anderson Scott
- Andora Janice
- Andredesz Carol
- Andrew Robert
- Andrews Dan
- Andrews Daniel
- Andrews Neil
- Andrews Stephanie
- Andriese Tim
- Anthouard Véronique
- Antonarakis Stylianos E.
- Anyalebechi Vivian
- Aoki Norie
- Apostolou Sinoula
- Apweiler Eva
- Arachchi Harindra
- Arai Rie
- Arbery Hazel
- Arcaina Marlon
- Arcaina Terisita
- Archer Beth
- Arellano Andre
- Arellano-Jones Perry
- Armbruster Jeff
- Armstrong Jon
- Arredondo Dilrukshi P.
- Arredondo Heather Hope
- Artiguenave François
- Asakawa Shuichi
- Asakawa Teruyo
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- Ashurst Jennifer
- Ashwell Robert
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- Aslanidis Cara
- Asomugha Chinwe O.
- Asuncion Lawreen
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- Atkinson Barry
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- Zhang Guohua
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- Zhang Haiqing
- Zhang Haiqing
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- Zhang Xianglin
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- Zhang Xiuqing
- Zhang Yan
- Zhang Yi
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- Zhang Yilin
- Zhang Ying
- Zhang Yuansen
- Zhang Yuzhi
- Zhang Zhengdong
- Zhao Hongmei
- Zhao Lijian
- Zhao Shenru
- Zhao Zhijing
- Zhen Zhicheng
- Zheng Haibo
- Zhong Ming
- Zhou Carol
- Zhou Haixia
- Zhou Jianling
- Zhou Nannan
- Zhou Xinfeng
- Zhou Yan
- Zhou Yang
- Zhou Yi
- Zhu Bingying
- Zhu Bofeng
- Zhu Fenghua
- Zhu Genfeng
- Zhu Genfeng
- Zhu Miao
- Zhu Ning
- Zhu Yongge
- Zhu Zhen
- Zhuang Shitao
- Zierten Deborah
- Zimmer Andrew
- Zody Michael C.
- Zollo Massimo
- Zorrilla Sara E.
- Zuo Lin
- Publication venue
- LSU Digital Commons
- Publication date
- 21/10/2004
- Field of study
The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead
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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
- Bagshaw Sean
- Baillie Kenneth
- Baker Evelyn
- Bakthavatsalam Dhanalakshmi
- Bamford Peter
- Banach Dorota
- Bannard-Smith Jonathan
- Barbazza Leanne
- Barber Russell
- Barge Deborah
- Barnes Nicky
- Baršić Bruno
- Bashyal Archana
- Basile Kim
- Bass Frances
- Bates Michelle
- Bauchmuller Kris
- Bean Sarah
- Beane Abigail
- Beane Abigail
- Beasley Richard
- Begin Phillipe
- Bellemare David
- Benettaib Fatna
- Benzekri Dalila
- Berdaguer Fernando Daniel
- Bergin Colin
- Berry Lindsay
- Berry Lindsay
- Berry Scott
- Berry Scott
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- Bhimani Zahra
- Bihari Shailesh
- Bihari Shilesh
- Binnie Alexandra
- Bion Julian
- Biradar Vishwanath
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- Cutler Sean
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- Daly Zoe
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- Davies Louisa
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- Day Christopher
- De Beaux Fiona
- De Bus Liesbet
- de Courcy-Golder Kim
- de Jager P
- de Jong Menno
- De Jong Menno
- de Jonge E
- de la Fuente Martos Carmen
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- Kalogirou Michael
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- Lawler Patrick
- Lawler Patrick R
- Lawless Patrick
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- Leaver Susannah
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- Lewis Roger
- Lewis Roger J
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- Litton Edward
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- Nair Priya
- Nay Mai-Anh
- Neal Matthew
- Nee Jens
- Netea Mihai
- Netherton Kimberley
- Neto Ary
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- O’Neill Aisling
- Page Valerie
- Paling A
- Panwar Rakshit
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- Parke Rachael
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- Polderman F
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- van Bentum Puijk Wilma
- van Bentum-Puijk Wilma
- van Bentum-Puijk Wilma
- van Beurden Marloes
- van de Veerdonk Frank
- van de Veerdonk Frank
- Van Der Heyden Kym
- van der Poll Tom
- van’t Hoff Willian
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- Vazquez-Grande Gloria
- Venkatesh Bala
- Venkatesh Balasubramanian
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- Verlander Mark
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- Victor Saji
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- Vowell Emma
- Vujaklija Brajković Ana
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- Walsh Tim
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- Warnock Majella
- Waterson Sharon
- Watkins Claire
- Watpool Irene
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- Webb Steve
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- Wedd Steve
- Weismann Dirk
- Weissman Alexandra
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- Wetherill Bill
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- Whitbread Jennifer
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- Williamson James
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- 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
The James Webb Space Telescope Mission
- Author
- Abbott Randy
- Abell James S.
- Abernathy Mark
- Abney Faith E.
- Abraham John G.
- Abraham Roberto
- Abul-Huda Yasin M.
- Acton Scott
- Adams Cynthia K.
- Adams Evan
- Adler David S.
- Adriaensen Maarten
- Aguilar Jonathan Albert
- Ahmed Mansoor
- Ahmed Nasif S.
- Ahmed Tanjira
- Alarcon Rafael Ramos
- Albat Rüdeger
- Albert Loïc
- Alberts Stacey
- Aldridge David
- Allen Mary Marsha
- Allen Shaune S.
- Altenburg Martin
- Altunc Serhat
- Alvarez Jose Lorenzo
- Ambrose Leslie L.
- Anandakrishnan Satya M.
- Andersen Gregory C.
- Anderson Harry James
- Anderson Jay
- Anderson Kristen
- Anderson Sara M.
- Aprea Julio
- Archer Benita J.
- Arenberg Jonathan W.
- Argyriou Ioannis
- Arribas Santiago
- Artigau Étienne
- Arvai Amanda Rose
- Atcheson Paul
- Atkinson Charles B.
- Averbukh Jesse
- Aymergen Cagatay
- Bacinski John J.
- Baggett Wayne E.
- Bagnasco Giorgio
- Baker Lynn L.
- Balzano Vicki Ann
- Banks Kimberly A.
- Baran David A.
- Barker Elizabeth A.
- Barrett Larry K.
- Barringer Bruce O.
- Barto Allison
- Bast William
- Baudoz Pierre
- Baum Stefi
- Beatty Thomas G.
- Beaulieu Mathilde
- Bechtold Kathryn
- Beck Tracy
- Beddard Megan M.
- Beichman Charles
- Bellagama Larry
- Bely Pierre
- Berger Timothy W.
- Bergeron Louis E.
- Bertch Maria D.
- Beskow Charlotte
- Betz Laura E.
- Biagetti Carl P.
- Birkmann Stephan
- Bjorklund Kurt F.
- Blackwood James D.
- Blazek Ronald Paul
- Blossfeld Stephen
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- Boegner Jr. Martin E.
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- Tufail Yasir
- Tumlinson Jason
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- Vernoy Michael R.
- Volk Kevin
- Voorzaat Piet
- Voyton Mark F.
- Vydra Ekaterina
- Waddy Darryl J.
- Waelkens Christoffel
- Wahlgren Glenn Michael
- Walker Jr. Frederick E.
- Wander Michel
- Warfield Christine K.
- Warner Gerald
- Wasiak Francis C.
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- Wehner James
- Weiler Kevin R.
- Weilert Mark
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- Wells Martyn
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- Whitehouse Paul
- Whiteleather Jennifer Margaret
- Whitman William Russell
- Williams Christina C.
- Willmer Christopher N. A.
- Willott Chris J.
- Willoughby Scott P.
- Wilson Andrew
- Wilson Debra
- Wilson Donna V.
- Windhorst Rogier
- Wislowski Emily Christine
- Wolfe David J.
- Wolfe Michael A.
- Wolff Schuyler
- Wondel Amancio
- Woo Cindy
- Woods Robert T.
- Worden Elaine
- Workman William
- Wright Gillian S.
- Wu Carl
- Wu Chi-Rai
- Wun Dakin D.
- Wymer Kristen B.
- Yadetie Thomas
- Yan Isabelle C.
- Yang Keith C.
- Yates Kayla L.
- Yeager Christopher R.
- Yerger Ethan John
- Young Erick T.
- Young Gary
- Yu Gene
- Yu Susan
- Zak Dean S.
- Zeidler Peter
- Zepp Robert
- Zhou Julia
- Zincke Christian A.
- Zonak Stephanie
- Zondag Elisabeth
- Álvarez-Márquez Javier
- Östlin Göran
- Publication venue
- Publication date
- 10/04/2023
- Field of study
Twenty-six years ago a small committee report, building on earlier studies,
expounded a compelling and poetic vision for the future of astronomy, calling
for an infrared-optimized space telescope with an aperture of at least 4m.
With the support of their governments in the US, Europe, and Canada, 20,000
people realized that vision as the 6.5m James Webb Space Telescope. A
generation of astronomers will celebrate their accomplishments for the life of
the mission, potentially as long as 20 years, and beyond. This report and the
scientific discoveries that follow are extended thank-you notes to the 20,000
team members. The telescope is working perfectly, with much better image
quality than expected. In this and accompanying papers, we give a brief
history, describe the observatory, outline its objectives and current observing
program, and discuss the inventions and people who made it possible. We cite
detailed reports on the design and the measured performance on orbit.Comment: Accepted by PASP for the special issue on The James Webb Space
Telescope Overview, 29 pages, 4 figure
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
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- 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
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- A Ganesan
- A Gardner
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- Alan Maclean
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- 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
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- B Sloan
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- 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
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- C Brantwood
- C Burnett
- C Castro Delgado
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- C Phillips
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- C Rishton
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- C Sicat
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- C Swan
- C Thompson
- C Thorpe
- C Tibke
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- 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
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- D Baptista
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- D Golden
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- D Hope
- D Horner
- D Kallon
- D Kaye
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- D Wright
- Daniela Francisci
- Daniella Coker
- Danilo Tacconi
- David A van Heel
- David Bennet
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- Debby Bogaert
- Derek Murphy
- Domenico A Coviello
- E Abaleke
- E Allan
- E Anastasescu
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- E Dooks
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- E Goff
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- E Gordon
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- F Anderson
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- Federico Anedda
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- Ferdinando Giannattasio
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- Furniss James
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- Stephanie Roberts
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- Summers Charlotte
- Susanna Croci
- Susanna Guerrini
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- Teresa Filshtein-Sonmez
- Thomas M Drake
- Thushan de Silva
- Tim Walsh
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- Tom Solomon
- Tony Wackett
- Trevor Paterson
- Tullio Trotta
- Turtle Lance
- U Poultney
- V Amin
- V Anumakonda
- V Bastion
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- V Irvine
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- V Linnett
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- V Parris
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- V Sarathy
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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
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 Carà 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
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- Bellemare David
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- Bendjemar Lynda
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- Bentley Andrew
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- 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
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- Birkinshaw Isobel
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- Blank Elisabeth
- Bleasdale John
- Bloomfield Jack
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- Boardman Melanie
- Boari Gianluca
- Bocher Simon
- Bociek Aneta
- Boivin Anne-Helene
- Boivin Anne-Hélène
- 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
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- Boué Yvonnick
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- Boyd Craig
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- Bracke Stephanie
- Bradbury Charlotte A.
- Bradley Paul
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- Bridges Sarah
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- Brochard Laurent
- Brodbeck Andreas
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- Brugman Curt
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- Brunkhorst Frank M.
- Brunskill Nigel
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- Campisi Josie
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- Carrier Marc
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- 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
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- 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
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- Williamson James D
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- 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 non–critically 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 (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days.
MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free 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 support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (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 support–free 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
31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two
- Author
- Abassi Yama
- Abelin Jennifer G
- Abolhalaj Milad
- Abraham Tara S
- Adam Ammar
- Adams David
- Adams Homer
- Adams Sarah F
- Adamus Tomasz
- Addepalli Murali
- Addepalli Murali
- Adjei Alex A
- Agapova Larissa
- Agarwala Sanjiv
- Ager Casey
- Aggarwal Charu
- Agnello Giulia
- Agudo Judith
- Aguilar Ethan G
- Aguilera Todd
- Ahamadi Malidi
- Ahn Yong-Oon
- Ahrens Eric T
- Aizer Ayal
- Ajina Reham
- Akerley Wallace
- Al-Muftah Mariam
- Albershardt Tina C
- Albershardt Tina C
- Albrekt Ann-Sofie
- Alekar Shilpa
- Alemany Ramon
- Alemany Ramon
- Alexander Brian
- Allbritton Omaira
- Allen Clint T
- Alley Evan W
- Allison James
- Allison James
- Allison James
- Alston Tesha
- Alt Jürgen
- Alters Susan
- Amatulli Michael
- Anand Snjezana
- Anand Snjezana
- Anand Snjezana
- Anderson Clark
- Anderson Mark
- Andersson Bengt
- Andre Pascale
- Andtbacka Robert H I
- Andtbacka Robert H I
- Angiuoli Sam
- Ansari Tameem
- Anthony Scott
- Antonarakis Emmanuel S
- Antonia Scott J
- Anwar Firoz
- Aquino-Michaels Keston
- Archer Jacob F
- Arina Ainhoa
- Armand Philippe
- Armenta Paul
- Armet Caroline M
- Arnoux Thomas
- Ascarateil Stephane
- Askmyr David
- Atkins Michael
- Atkins Michael B
- Atkinson Victoria
- Au Katrina
- Autio Karen A
- Awad Mark
- Bagarazzi Mark
- Bai Dina
- Baia Gilson
- Baird Jason
- Bajaj Anshika
- Balatoni Timea
- Balboni Tracy
- Balch Leslie
- Bang Andrew
- Bao Riyue
- Bao Yangyi
- Bao Yangyi
- Barakat David
- Barberi Theresa
- Barker Christopher A
- Barnea Eytan
- Barras David
- Bartkowiak Todd
- Bartlett David
- Bartlett David
- Bartlett David
- Bartlett David
- Barton Sunjay M
- Barve Minal
- Bauer Todd
- Bauer Todd W
- Bauman Julie
- Baumgaertner Petra
- Bauml Joshua
- Beceren-Braun Figen
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- Becker Annette
- Beckers Johannes
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- Bedognetti Davide
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- Beltran Pedro
- Bender Lewis H
- Bender Steven
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- Benz Steven
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- Berry John S
- Berzofsky Jay A
- Bhardwaj Nina
- Bian Zhen
- Bianco Alberto
- Biediger Ronald J
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- Bigley Alison
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- Bischoff Helge
- Blake Zoe
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- Bommareddy Praveen K
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- Booth Jamie
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- Bose Nandita
- Bossenmaier Birgit
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- Bullock Kim
- Bullock Kim
- Burova Elena
- Burrill Joel
- Bussler Holm
- Butterfield Lisa H
- Butterfield Lisa H
- Byrne-Steele Miranda
- Cagney Daniel
- Calderon Hugo
- Callahan Margaret K
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- Chang Joe
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- Chang Thomas
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- Chapelin Fanny
- Chaplin Jenny
- Chappel Scott C
- Charych Deborah H
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- Cho Charles
- Chongyung Fang
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- Choueiri Toni K
- Choy Carmen
- Clark Joseph I
- Clavijo Paul E
- Clifton Guy T
- Clynes Raphael
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- Conwell Darwin
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- Coukos George
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- Coussens Lisa M
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- Craggs Graham
- Craig Andrew
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- Crooks James
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- Daud Adil
- David Justin M
- Davies Bronwyn
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- de Groot Patricia
- de Gruijl Tanja
- De Henau Olivier
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- de Silva Suresh
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- Deacon Donna H
- DeBenedette Mark
- DeBenedette Mark
- Declerck Paul
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- Decock Julie
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- Delgoffe Greg
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- Delgoffe Greg M
- Delgoffe Greg M
- Delogu Lucia
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- Deng Liang
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- Dhupkar Pooja
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- Facciponte John
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- Shamalov Katerina
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- Stefano Pierini
- Steggerda Susanne
- Stein Paul L
- Stelow Edward B
- Sternby Malin
- SternJohn Julius
- Stewart Al
- Stock Wendy
- Stone Geoffrey W
- Stosnach Claudia
- Straub Tobias
- Straus Jane
- Streiner Nicole
- Ståhle Magnus
- Su Yu-Lin
- Sudarshan Naremaddepalli
- Sugarbaker David
- Sukari Ammar
- Sultan Hussein
- Sun Shaoli
- Sundararaman Srividya
- Sung Leonard
- Suresh Rahul
- Surguladze David
- Suryawanshi Satyendra
- Suryawanshi Satyendra
- Suzuki Akiko
- Suzuki Ryuji
- Sweis Randy F
- Taback Bret
- Tagliaferri Mary
- Talbert Erin
- Tallarico John
- Tan Joanne B
- Tan Joanne B L
- Tan Wei
- Tan Yann C
- Tanaka Maki
- Tang Chad
- Tannir Nizar M
- Tannir Nizar M
- Taylor Allison
- Taylor Matthew
- Tcherepanova Irina
- ter Meulen Jan
- ter Meulen Jan
- Terabe Masaki
- Terabe Masaki
- Termini James
- Tetzlaff Michael
- Tewary Poonam
- Thakurta Anjan
- Thayer Matt
- Theodoraki Marie-Nicole
- Thimme Robert
- Thomas Portia
- Thomas Remy
- Thomas Vincent
- Thompson John A
- Thounaojam Menaka
- Thounaojam Menaka
- Thurston Gavin
- Tighe Rober
- Tilahun Ashenafi
- Tillé Laure
- Timmerman John
- Tipton Kimberly A
- Tipton Kimberly A
- Tognon Christina E
- Tomai Mark A
- Toms Anne
- Torno Sebold
- Torrey Heather
- Torti Vince
- Toth Laszlo
- Trager James B
- Trappey Alfred F
- Trivedi Sumita
- Truesdell Peter
- Tsang Kwong
- Tsang Kwong
- Tsang Kwong Y
- Tsaparikos Konstantinos
- Tsouko Efrosini
- Tsujikawa Takahiro
- Tsujikawa Takahiro
- Tsujikawa Takahiro
- Tuck David
- Tumang Joseph
- Tumang Joseph
- Turbitt William J
- Turk Andrew T
- Tyner Jeffery W
- Tähtinen Siri
- Tähtinen Siri
- Uecker Darrin
- Uecker Darrin
- Uecker Darrin
- Ugel Stefano
- Ugel Stefano
- Uhlik Mark
- Ujhelyi Mihaly
- Ullenhag Gustav
- Unfricht Darryn
- Ungerleider Richard
- Urban Julie
- Urban Julie
- Valsesia-Wittmann Sandrine
- Valsesia-Wittmann Sandrine
- Van der Meijs Pien
- van Vugt Marianne
- van Zutphen Mariëlle
- Vanamee Eva
- Vanderslice Peter
- VanderVeen Laurie
- Vanpouille-Box Claire I
- VanVlasselaer Peter
- Varhegyi Nikole
- Vasilakos John P
- Vaske Charles
- Vassilev Lotta
- Velcheti Vamsidhar
- Velculescu Victor
- Verma Amita
- Verma Amita
- Vetto John
- Vianden Christina
- Vietsch Eveline E
- Vignali Dario
- Vignali Dario
- Vogel Katharina
- Volkmuth Wayne
- Volz Barbara
- vonEbyen Rie
- Vreeland Timothy J
- Vu Tuyen
- Wada Hiroshi
- Wagtmann Nicolai
- Waldman Michelle
- Waldman Scott A
- Waller John
- Wallraven Gladice
- Walsh Richard
- Walters Ian B
- Wang Ena
- Wang Ena
- Wang Hongjie
- Wang Ping
- Wang Shangzi
- Wang Weiyi
- Wang Ximi K
- Wang Yi
- Wang Ziming
- Ward Stephen T
- Waugh Katherine
- Weber Amy
- Wehler Thomas
- Wei Spencer
- Weichselbaum Ralph R
- Weiner David
- Weiner Louis M
- Weinstein Gregory
- Weiss Christian
- Welden Scott
- Wellstein Anton
- Welsh James
- Wennerberg Erik
- Wenthe Jessica
- Wenthe Jessica
- Werner Lauryn R
- West Brian
- West James
- West James
- Wheatley Courtney
- Whetstone Ryan
- Whetstone Ryan
- White James
- White-Stern Ashley
- Whiteside Melinda
- Whiting Chan C
- Whiting Chan C
- Wicha Max S
- Wicha Max S
- Wieckowski Eva
- Wijeratne Kithsiri
- Wilhite Tyler
- Wilkinson Robert W
- Wilkinson Robert W
- Williams Matthew
- Williamson Kevin
- Willingham Stephen
- Wilson James M
- Wilson Nicholas
- Winters Kevin
- Withers Sita
- Wittig Burghardt
- Wolchok Jedd D
- Wolchok Jedd D
- Wolchok Jedd D
- Wolchok Jedd D
- Wolchok Jedd D
- Wolfreys Alison
- Won Haejung
- Wong Chihunt
- Wong Chihunt
- Wong Deborah J
- Wong Gabriel
- Wong Kenneth R
- Wong Kenneth R
- Wong Michael K
- Wood Laura
- Woodside Darren G
- Workman Creg
- Wu Bill X
- Wu Dongyun
- Wu Jennifer
- Wu Yeting
- Wyant Timothy
- Wythes Martin
- Xi Biao
- Xia Leiming
- Xia Yang
- Xia Yang
- Xiang Bo
- Xiao Christine
- Xiao Hong
- Xiao Zhilan
- Xu Chun-wei
- Xu Chunxiao
- Xu Guifen
- Xu Xiaomei
- Xu Xin
- Xu Ya-Ming
- Xu Yitong
- Yadav Mahesh
- Yagiz Kader
- Yamashiro Darrell J
- Yan Jian
- Yang Chou
- Yang Ning
- Yang Zane
- Yano Hiroshi
- Yao Shiyin
- Ye Yun-bin
- Yin Catherine
- Ylösmäki Erkko
- Ylösmäki Erkko
- Young Gregory
- Young Gregory
- Young Kristina
- Young Rob
- Young Steve W
- Young Steve W
- Youssoufian Hagop
- Yu Huakui
- Yu Ling
- Yu Naichen
- Zafar Sadia
- Zalevsky Jonathan
- Zalevsky Jonathan
- Zalevsky Jonathan
- Zalevsky Jonathan
- Zappasodi Roberta
- Zappasodi Roberta
- Zauderer Maurice
- Zeh Herbert
- Zelenetz Andrew D
- Zeng Weiping
- Zeng Xue
- Zha Yuanyuan
- Zhang Danhui
- Zhang Jing
- Zhang Ping
- Zhang Qifang
- Zhang Shannon S
- Zhang Theresa
- Zhang Winter
- Zhang Yanping
- Zhao Fei
- Zhao Leyna
- Zhao Xingli
- Zheng Lianxing
- Zheng Wenxin
- Zheng Xianxian
- Zheng Yi
- Zhong Hong
- Zhou Li
- Zhou Xiangjun
- Zippelius Alfred
- Zloza Andrew
- Zloza Andrew
- Zloza Andrew
- Zloza Andrew
- Zloza Andrew
- Zou Jun
- Zuba-Surma Ewa
- Zubkova Olga
- Zureikat Amer
- Publication venue
- 'Springer Science and Business Media LLC'
- Publication date
- 01/01/2016
- Field of study
Background
The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd.
Methods
We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background.
Results
First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001).
Conclusions
In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival
Blood Myo-Inositol Concentrations in Preterm and Term Infants
- Author
- Archer Stephanie Wilson
- Auten Kathy J.
- Ball M. Bethany
- Brion Luc P.
- Caplan Michael S.
- Cotten C. Michael
- Das Abhik
- Frantz Ivan D.
- Goldberg Ronald N.
- Hallman N. Mikko K.
- Hensman Angelita M.
- Herron Dianne E.
- Higgins Rosemary D.
- Jobe Alan H.
- Laptook Abbot R.
- Lemons James A.
- Lugo Ralph A.
- Nolen Tracy L.
- Oh William
- O’Shea T. Michael
- Phelps Dale L.
- Poindexter Brenda B.
- Van Meurs Krisa P.
- Ward Robert M.
- Watterberg Kristi L.
- Wilson Leslie Dawn
- Zaccaro Daniel J.
- Zaterka-Baxter Kristin M.
- Publication venue
- 'Springer Science and Business Media LLC'
- Publication date
- 01/01/2020
- Field of study
© 2020, The Author(s), under exclusive licence to Springer Nature America, Inc. Objective: To describe relationship between cord blood (representing fetal) myo-inositol concentrations and gestational age (GA) and to determine trends of blood concentrations in enterally and parenterally fed infants from birth to 70 days of age. Design/Methods: Samples were collected in 281 fed or unfed infants born in 2005 and 2006. Myo-inositol concentrations were displayed in scatter plots and analyzed with linear regression models of natural log-transformed values. Results: In 441 samples obtained from 281 infants, myo-inositol concentrations varied from nondetectable to 1494 μmol/L. Cord myo-inositol concentrations decreased an estimated 11.9% per week increase in GA. Postnatal myo-inositol concentrations decreased an estimated 14.3% per week increase in postmenstrual age (PMA) and were higher for enterally fed infants compared to unfed infants (51% increase for fed vs. unfed infants). Conclusions: Fetal myo-inositol concentrations decreased with increasing GA. Postnatal concentrations decreased with increasing PMA and were higher among enterally fed than unfed infants
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Cortisol awakening response and developmental outcomes at 6–7 years in children born extremely preterm
- Author
- Adams-Chapman Ira
- Alksninis Barbara
- Ambalavanan Namasivayam
- Archer Stephanie Wilson
- Ashley Patricia
- Auten Kathy J
- Ball M Bethany
- Bhola Monika
- Blaisdell Carol J
- Bottcher Diane
- Brussa Ana
- Buchter Susie
- Caplan Michael S
- Carlo Waldemar A
- Carlton David P
- Carter Sheena
- Collins Monica V
- Cosby Shirley S
- Cotten C Michael
- Das Abhik
- DeAnda Maria Elena
- Dempsey Allison G
- DiFiore Julie
- Domanovich Kristy
- Duncan Andrea F
- Fanaroff Avroy A
- Fiascone John M
- Finer Neil N
- Fisher Kimberley A
- Foy Katherine A
- Frantz Ivan D
- Freedman Sharon F
- Friedman Harriet G
- Fritz Sobha
- Gantz Marie G
- Goldberg Ronald N
- Goldstein Ricki F
- Goodlin Gabrielle T
- Granger Douglas A
- Gustafson Kathryn E
- Hale Ellen C
- Hammond Jane A
- Harmon Heidi M
- Hensman Angelita M
- Herron Dianne E
- Higgins Rosemary D
- Hines Abbey C
- Hutchinson Amy K
- Jobe Alan H
- John Janice
- Johnson Katharine
- Jones Patrick M
- Kennedy Kathleen A
- Keszler Mary Lenore
- Kiser Carin R
- Knoll Andrea M
- Kurfiss Anne
- Laptook Abbot R
- LaRossa Maureen Mulligan
- Leach Theresa M
- Lillie M Layne
- Little Emilee
- Loggins Yvonne
- Lohmeyer Melody B
- MacKinnon Brenda L
- Malcolm William F
- McGowan Elisabeth C
- McGowan Elisabeth C
- Newman Jamie E
- Newman Nancy S
- Nylen Ellen
- O’Donnell Auman Jeanette
- Papile Lu-Ann
- Payne Allison
- Phillips Vivien A
- Piazza Anthony J
- Poindexter Brenda B
- Polin Richard A
- Poole W Kenneth
- Sibley Cecelia
- Siddiki Saba
- Siner Bonnie S
- Smiley Lucy
- Smith Leigh Ann
- Sokol Gregory M
- Sperry Daniel K
- Stevenson David K
- Stoll Barbara J
- Tyson Jon E
- Van Meurs Krisa P
- Vieira Elisa
- Wallace David K
- Wallace Dennis
- Walsh Michele C
- Watson Victoria E
- Whitley Sally
- Wilson Leslie D
- Wilson-Costello Deanne E
- Yalcinkaya Gulgun
- Zadell Arlene
- Publication venue
- eScholarship, University of California
- Publication date
- 01/02/2023
- Field of study
BackgroundExtremely preterm (EPT) birth has been related to dysregulation of stress responses and behavioral/learning problems at school age. Early adverse experiences can blunt HPA axis reactivity. We hypothesized that an attenuated cortisol awakening response would be associated with developmental and behavioral problems at school age in EPT children.MethodsThis secondary analysis of a sub-cohort of the SUPPORT study included children born between 24 and 27 weeks, evaluated at 6-7 years with a neurodevelopmental battery and cortisol measures. Differences were tested between EPT and a term-born group. Relationships of cortisol awakening response to test scores were analyzed.ResultsCortisol was measured in 110 EPT and 29 term-born 6-7 year olds. Unadjusted WISC-IV and NEPSY-II scores were significantly worse among EPT children only. Conners Parent Rating Scale behavior scores were significantly worse among EPT children. After adjusting for covariates, blunted cortisol awakening responses were found to be associated with poorer scores on memory tests and greater problems with inattention for the EPT group (p < 0.05) only.ConclusionsAmong children born EPT, we identified an association of blunted cortisol awakening response with memory and inattention problems. This may have implications related to stress reactivity and its relationship to learning problems in children born EPT.ClinicaltrialsGov idExtended Follow-up at School Age for the SUPPORT Neuroimaging and Neurodevelopmental Outcomes (NEURO) Cohort: NCT00233324.ImpactIn children born EPT, stress reactivity may have a relationship to learning problems. Cortisol awakening response should be a component for follow-up in EPT born children. Components of executive function, such as memory and attention, are related to stress reactivity
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Umbilical Cord Milking vs Delayed Cord Clamping and Associations with In-Hospital Outcomes among Extremely Premature Infants
- Author
- Ambalavanan Namasivayam
- Archer Stephanie Wilson
- Auman Jeanette O'Donnell
- Ball M Bethany
- Bann Carla M
- Baugher Hallie
- Bell Edward F
- Bernhardt Janice
- Bose Carl L
- Bose Gennie
- Bottcher Diane I
- Bremer Andrew A
- Carlo Waldemar A
- Carlton David P
- Chanlaw Teresa
- Chock Valerie Y
- Clark Cindy
- Clark Erna
- Colaizy Tarah T
- Collins Monica V
- Cosby Shirley S
- Cotten C Michael
- Das Abhik
- Davis Alexis S
- DeMauro Sara B
- Devaskar Uday
- Eason Elizabeth
- Eggleston Barry
- Ellsbury Dan L
- Finkle Joanne
- Fisher Kimberley A
- Foglia Elizabeth E
- Gabrio Jenna
- Gaetano Lisa
- Gantz Marie G
- Garg Meena
- Gauldin Cheri
- Geller Rachel
- Goldberg Ronald N
- Grisby Cathy
- Gutentag Julie
- Hall Donna
- Handley Sara C
- Hensman Angelita M
- Herron Dianne E
- Hibbs Anna Maria
- Higgins Rosemary D
- Holmes Anne
- Jadcherla Sudarshan R
- Kennedy Kathleen A
- Keszler Martin
- Khan Amir M
- Kicklighter Stephen D
- Kirker Kristin
- Knutson Allison
- Kumbhat Neha
- Lakshminrusimha Satyan
- Laptook R
- Laughon Matthew M
- Leblond David
- Loggins Yvonne
- Luzader Patricia
- Mackie Colleen
- Martin Karen
- McCool Jacqueline
- McDavid Georgia E
- McNair Tara
- Merhar Stephanie L
- Nelin Leif D
- Network Generic Database Subcommittee of the National Institute of Child Health and Human Development Neonatal Research
- Pallotto Eugenia K
- Parimi Prabhu S
- Park Courtney
- Patel Ravi M
- Pedrozza Claudia
- Poindexter Brenda B
- Polin Richard A
- Proud Melinda S
- Reichert Elizabeth N
- Rhodes-Ryan Ginger
- Schibler Kurt
- Shadd Julie C
- Sokol Gregory M
- St. Pierre Lucille
- Stein Melanie
- Stephens Emily K
- Stevenson David K
- Sánchez Pablo J
- Truog William E
- Tyson Jon E
- Van Meurs Krisa P
- Vieira Elisa
- Wallace Dennis
- Walsh Michele C
- Watterberg Kristi L
- White Donna
- Williams R Jordan
- Wright Sharon L
- Wyckoff Myra H
- Zaterka-Baxter Kristin M
- Publication venue
- eScholarship, University of California
- Publication date
- 01/05/2021
- Field of study
ObjectiveTo compare in-hospital outcomes after umbilical cord milking vs delayed cord clamping among infants <29 weeks of gestation.Study designMulticenter retrospective study of infants born <29 weeks of gestation from 2016 to 2018 without congenital anomalies who received active treatment at delivery and were exposed to umbilical cord milking or delayed cord clamping. The primary outcome was mortality or severe (grade III or IV) intraventricular hemorrhage (IVH) by 36 weeks of postmenstrual age (PMA). Secondary outcomes assessed at 36 weeks of PMA were mortality, severe IVH, any IVH or mortality, and a composite of mortality or major morbidity. Outcomes were assessed using multivariable regression, incorporating mortality risk factors identified a priori, confounders, and center. A prespecified, exploratory analysis evaluated severe IVH in 2 gestational age strata, 22-246/7 and 25-286/7 weeks.ResultsAmong 1834 infants, 23.6% were exposed to umbilical cord milking and 76.4% to delayed cord clamping. The primary outcome, mortality or severe IVH, occurred in 21.1% of infants: 28.3% exposed to umbilical cord milking and 19.1% exposed to delayed cord clamping, with an aOR that was similar between groups (aOR 1.45, 95% CI 0.93, 2.26). Infants exposed to umbilical cord milking had higher odds of severe IVH (19.8% umbilical cord milking vs 11.8% delayed cord clamping, aOR 1.70 95% CI 1.20, 2.43), as did the 25-286/7 week stratum (14.8% umbilical cord milking vs 7.4% delayed cord clamping, aOR 1.89 95% CI 1.22, 2.95). Other secondary outcomes were similar between groups.ConclusionsThis analysis of extremely preterm infants suggests that delayed cord clamping is the preferred practice for placental transfusion, as umbilical cord milking exposure was associated with an increase in the adverse outcome of severe IVH.Trial registrationClinicalTrials.gov: NCT00063063