857 research outputs found
hERG Gating Microdomains Defined by S6 Mutagenesis and Molecular Modeling
- Publication venue
- The Rockefeller University Press
- Publication date
- Field of study
Human ether-à-go-go–related gene (hERG) channels mediate cardiac repolarization and bind drugs that can cause acquired long QT syndrome and life-threatening arrhythmias. Drugs bind in the vestibule formed by the S6 transmembrane domain, which also contains the activation gate that traps drugs in the vestibule and contributes to their efficacy of block. Although drug-binding residues have been identified, we know little about the roles of specific S6 residues in gating. We introduced cysteine mutations into the hERG channel S6 domain and measured mutational effects on the steady-state distribution and kinetics of transitions between the closed and open states. Energy-minimized molecular models based on the crystal structures of rKv1.2 (open state) and MlotiK1 and KcsA (closed state) provided structural contexts for evaluating mutant residues. The majority of mutations slowed deactivation, shifted conductance voltage curves to more negative potentials, or conferred a constitutive conductance over voltages that normally cause the channel to close. At the most intracellular extreme of the S6 region, Q664, Y667, and S668 were especially sensitive and together formed a ringed domain that occludes the pore in the closed state model. In contrast, mutation of S660, more than a full helical turn away and corresponding by alignment to a critical Shaker gate residue (V478), had little effect on gating. Multiple substitutions of chemically distinct amino acids at the adjacent V659 suggested that, upon closing, the native V659 side chain moves into a hydrophobic pocket but likely does not form the occluding gate itself. Overall, the study indicated that S6 mutagenesis disrupts the energetics primarily of channel closing and identified several residues critical for this process in the native channel
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
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- Baker Pauline
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- Banaras Azra
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- Bhatnagar Priya
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- du Plessis Johannes
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- Salih Isam
- Sally Moore
- Sandercock Peter A G
- Sangombe Mirriam
- Sangster Graeme
- Sanyal Ranjan
- Sarah Procter
- Sarah Procter
- Sattar Naweed
- Sattar Saira
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- Saulat Afaq
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- Siddiq Muhammad
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- Sims Don
- Singh Arun
- Sinha Devesh
- Skinner Helen
- Slade Peter
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- Smith Fiona
- Smith Gemma Marie
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- Sprigg Nikola
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- Stafford Samantha
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- 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
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- Sutton Claire
- Sutton Patrick
- Sutton Victoria
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- Tandy Jane
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- 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
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- 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
Psychosocial impact of undergoing prostate cancer screening for men with BRCA1 or BRCA2 mutations.
- Author
- Aaronson Neil K
- Adank Muriel A
- Amor David
- Andrews Lesley
- Anjum Uruj
- Aprikian Armen
- Araujo Luis
- Ardern-Jones Audrey
- Arun Banu
- Ausems Margreet GEM
- Awatagiri Kasturi
- Balmana Judith
- Bambury Richard
- Bancroft Elizabeth
- Bancroft Elizabeth K
- Bangma Chris
- Bartlett Marion
- Barwell Julian
- Basevitch Alon
- Bealin Lisa
- Ben-Yehoshua Sagi Josefsberg
- Bermingham Nicola
- Birt Angela
- Bojeson Anders
- Boon Melanie
- Boshari Talia
- Bowman Michelle
- Brady Angela
- Brennhovd Bjorn
- Brewer Carole
- Brice Glen
- Bulman Barbara
- Burgess Lucy
- Burke Jo
- Buys Saundra
- Buys Saundra S
- Caanen BAH
- Capella Gabriel
- Carlsson Stefan
- Castro Elena
- Catto James
- Chamberlain Anthony
- Chapman Cyril
- Chen-Shtoyerman Rakefet
- Chong Michael
- Clowes Virginia
- Cogley Lyn
- Cole Trevor
- Compton Cecilia
- Conner Tom
- Cook Jackie
- Cooney Kathy
- Copakova Lucia
- Cornford Philip
- Costello Philandra
- Cruger Dorthe
- Cummings Carole
- Cybulski Cezary
- D'Mello Lucia
- Davidson Rosemarie
- Davis John W
- Dearing Audrey
- Dearnaley David
- Dechet Christopher
- Devlin Gemma
- Dias Alex
- Dineen Amy
- Domchek Susan
- Donaldson Alan
- Dorkins Huw
- Douglas Fiona
- Duffy Jessica
- Duncan Alexis
- Eccles Diana
- Eccles Diana M
- Eeles Rosalind
- Eeles Rosalind A
- Ekdahl Karl-Johan
- Ellery Natalie
- Esquena Salvador
- Evans D Gareth
- Evans David Gareth
- Evans Gareth
- Everest Sarah
- Eyfjord Jorunn
- Falconer Alison
- Farrell Michael
- Fisas David
- Fleming-Brown D
- Foster Christopher
- Foulkes William
- Friedman Eitan
- Frydenberg Mark
- Gadea Neus
- Gallagher David
- Gallagher Fergal
- Garcia Lynda
- Gay Simona
- George Angela
- Gerdes Anne-Marie
- Ghonge Sujata
- Giri Veda
- Gleeson Margaret
- Glover Wayne
- Goldgar David
- Goncalves Nuno
- Goodman Selina
- Gott Hannah
- Greenhalgh Lynn
- Griebsch C
- Griffiths Julie
- Grindedal Eli Marie
- Gronberg Henrik
- Gross Laura
- Gurasashvili Jana
- Halliday Dorothy
- Hamdy Freddie C
- Hammond Carrie
- Hanslien Eldbjorg
- Hanson Helen
- Harris Marion
- Hart Rachel
- Heaton Tricia
- Helderman-van den Enden A Paula TJM
- Helfand Brian T
- Henderson Alex
- Henrique Rui
- Hill Kathryn
- Hjalm-Eriksson Marie
- Hodgson Shirley
- Hoffman Jonathan
- Homfray Tessa
- Hook Nicole
- Howell Alice
- Howson Joanne
- Huber Camilla
- Hulick Peter
- Hunt Clare
- Ingram Stuart
- Islam Farah
- Jacobs Chris
- James Paul
- Jensen Thomas
- Jobson Irene
- Johannsson Oskar
- Johannsson Oskar Thor
- Kaemba Beckie
- Kast K
- Kaul Karen
- Kemp Zoe
- Khoo Vincent
- Kiemeney Bart
- Kiernan Ingrid
- Kiesel Vicki
- Kirk Judy
- Kockelbergh Roger
- Kohut Kelly
- Kosicka-Slawinska Monika
- Kote-Jarai Zsofia
- Kowtal Pradnya
- Krajc Mateja
- Kulkarni Anju
- Kumar Pardeep
- Lam Jimmy
- Langman Caroline
- Leibovici Dan
- Lilja Hans
- Liljegren Annelie
- Lindeman Geoffrey
- Longmuir Mark
- Lubinski Jan
- Maehle Lovise
- Magnani Tiziana
- Maia Sofia
- Male Alison
- Mascarenhas Lyon
- McBride Donna
- McGaughran Julie
- McGuire Michael
- McKinley Joanne
- Medvik Heidi
- Melville Athalie
- Melzer Ehud
- Mencias Mark
- Mercer Catherine
- Mikropoulos Christos
- Millard Richard
- Miller Cathy
- Millner Alan
- Mitchell Gillian
- Mitra Anita
- Moller Pal
- Mom Jaswant
- Mora Josefina
- Morote Juan
- Morton Catherine
- Moss Cathryn
- Moynihan Clare
- Mulgund Gouri
- Murphy Declan
- Murphy Morgan
- Murthy Vedang
- Myhill Kathryn
- Mzazi Shumikazi
- Nadolski Maria
- Nevitt Louise
- Newcombe Barbara
- Newlin Anna
- Nicholls Cassandra
- Nicolai Nicola
- Nogueira Pedro
- O'Connell Shona
- Obeid Elias
- Offman Judith
- Ogden Chris
- Okoth Linda
- Oldenburg Rogier A
- Oliveira Jorge
- Ong Kai-Ren
- Oosterwijk Jan C
- Osther Palle
- Pachter Nicholas
- Paez Edgar
- Page Elizabeth
- Page Elizabeth C
- Patel Manish
- Patel Nafisa
- Paterson Joan
- Patterson Briony
- Pearce Allison
- Peixoto Ana
- Petelin Lara
- Pichert Gabriella
- Pope Jennifer
- Pope Jenny
- Poplawski Nicola
- Potter Alison
- Poultney Una
- Powers Jacquelyn
- Radice Paolo
- Ramon y Cajal Teresa
- Randhawa Kashmir
- Rees Katie
- Reinholtz Cherylin
- Rennert Gad
- Renton Caroline
- Rhiem Kerstin
- Richardson Kate
- Ringleberg Janneke
- Rosario Derek
- Rosario Derek J
- Rose Sarah
- Rothwell Jeanette
- Rubinstein Wendy S
- Ruijs Marielle WG
- Rustgi Neil
- Salinas Monica
- Sarin Rajiv
- Sattar Ayisha
- Saya Sibel
- Schmutzler Rita
- Schofield Lyn
- Scott Rodney
- Searle Anne
- Seixas Manuela
- Selkirk Christina Hutten
- Shackleton Kylie
- Shanley Sue
- Shaw Adam
- Shevrin Daniel
- Sidat Zahirah
- Side Lucy
- Siguake Kas
- Simon Kate
- Skytte Anne-Bine
- Smyth Courtney
- Snape Katie
- Souto Joao Paulo
- Spigelman Allan
- Stapleton Alan
- Stayner Barbara
- Stefansdottir Vigdis
- Stephenson Robert
- Stoffel Elena
- Stricker Phillip
- Strom Sara
- Suri Mohnish
- Susman Rachel
- Suthers Graeme
- Sutton Vivienne
- Swindle Peter
- Tan Hui Meng
- Taylor Amy
- Taylor Louise
- Taylor Natalie
- Teixeira Manuel
- Teo Soo Hwang
- Thomas Sarah
- Thompson Alan
- Thong Meow Keong
- Tidey Lizzie
- Tischkowitz Marc
- Tomkins Sue
- Tondering Majbritt Kure
- Torokwa Audrey
- Townshend Sharron
- Treherne Katy
- Tricker Karen
- Tripathi Vishakha
- Tucker Katherine
- Umez-Eronini Nkem
- Valdagni Riccardo
- Van As Nicholas
- van Asperen Christi
- van der Luijt Rob B
- van Os Theo
- van Zelst-Stams Wendy
- Vasen Hans
- Venne Vickie
- Vogel Kristen
- Vrecar Alenka
- Walker Lisa
- Ward Robyn
- Watson Michelle
- Watt Cathy
- Weiss Shelly
- Weissman Scott
- Wiggins Jennifer
- Wihler Petra
- Williams Rachel
- Wise Gillian
- Wokolorczyk Dominika
- Woodhouse Christopher
- Yamamura Yuko
- Yesildag Pembe
- Yoon Sook-Yee
- Zgajnar Janez
- Publication venue
- BJU Int
- Publication date
- 26/05/2018
- Field of study
OBJECTIVES: To report the baseline results of a longitudinal psychosocial study that forms part of the IMPACT study, a multi-national investigation of targeted prostate cancer (PCa) screening among men with a known pathogenic germline mutation in the BRCA1 or BRCA2 genes. PARTICPANTS AND METHODS: Men enrolled in the IMPACT study were invited to complete a questionnaire at collaborating sites prior to each annual screening visit. The questionnaire included sociodemographic characteristics and the following measures: the Hospital Anxiety and Depression Scale (HADS), Impact of Event Scale (IES), 36-item short-form health survey (SF-36), Memorial Anxiety Scale for Prostate Cancer, Cancer Worry Scale-Revised, risk perception and knowledge. The results of the baseline questionnaire are presented. RESULTS: A total of 432 men completed questionnaires: 98 and 160 had mutations in BRCA1 and BRCA2 genes, respectively, and 174 were controls (familial mutation negative). Participants' perception of PCa risk was influenced by genetic status. Knowledge levels were high and unrelated to genetic status. Mean scores for the HADS and SF-36 were within reported general population norms and mean IES scores were within normal range. IES mean intrusion and avoidance scores were significantly higher in BRCA1/BRCA2 carriers than in controls and were higher in men with increased PCa risk perception. At the multivariate level, risk perception contributed more significantly to variance in IES scores than genetic status. CONCLUSION: This is the first study to report the psychosocial profile of men with BRCA1/BRCA2 mutations undergoing PCa screening. No clinically concerning levels of general or cancer-specific distress or poor quality of life were detected in the cohort as a whole. A small subset of participants reported higher levels of distress, suggesting the need for healthcare professionals offering PCa screening to identify these risk factors and offer additional information and support to men seeking PCa screening
Prevalence and architecture of de novo mutations in developmental disorders.
- Author
- Ahmed Munaza
- Aitken Stuart
- Akawi Nadia
- Alvi Mohsan
- Ambridge Kirsty
- Anjum Uruj
- Archer Hayley
- Armstrong Ruth
- Awada Jana
- Balasubramanian Meena
- Banka Siddharth
- Baralle Diana
- Barnicoat Angela
- Barrett Daniel M.
- Barrett Jeffrey C.
- Batstone Paul
- Baty David
- Bayzetinova Tanya
- Bennett Chris
- Berg Jonathan
- Bernhard Birgitta
- Bevan A. Paul
- Bitner-Glindzicz Maria
- Blair Edward
- Blyth Moira
- Bohanna David
- Bourdon Louise
- Bourn David
- Bradley Lisa
- Brady Angela
- Brent Simon
- Brewer Carole
- Brunstrom Kate
- Bunyan David J.
- Burn John
- Canham Natalie
- Castle Bruce
- Chandler Kate
- Chatzimichali Elena
- Cilliers Deirdre
- Clarke Angus
- Clasper Susan
- Clayton Stephen
- Clayton-Smith Jill
- Clowes Virginia
- Coates Andrea
- Cole Trevor
- Colgiu Irina
- Collins Amanda
- Collinson Morag N.
- Connell Fiona
- Cooper Nicola
- Cox Helen
- Cresswell Lara
- Cross Gareth
- Crow Yanick
- D'Alessandro Mariella
- Dabir Tabib
- Davidson Rosemarie
- Davies Sally
- de Vries Dylan
- Dean John
- Deshpande Charu
- Devlin Gemma
- Dixit Abhijit
- Dobbie Angus
- Donaldson Alan
- Donnai Dian
- Donnelly Carina
- Donnelly Deirdre
- Douglas Angela
- Douzgou Sofia
- Duncan Alexis
- Eason Jacqueline
- Ellard Sian
- Ellis Ian
- Elmslie Frances
- Evans Karenza
- Everest Sarah
- Fendick Tina
- Firth Helen V.
- Fisher Richard
- Fitzgerald Tomas W.
- FitzPatrick David R.
- Flinter Frances
- Foulds Nicola
- Fry Andrew
- Fryer Alan
- Gardiner Carol
- Gaunt Lorraine
- Ghali Neeti
- Gibbons Richard
- Gill Harinder
- Goodship Judith
- Goudie David
- Gray Emma
- Green Andrew
- Greene Philip
- Greenhalgh Lynn
- Gribble Susan
- Harrison Lucy
- Harrison Rachel
- Harrison Victoria
- Hawkins Rose
- He Liu
- Hellens Stephen
- Henderson Alex
- Hewitt Sarah
- Hildyard Lucy
- Hobson Emma
- Holden Simon
- Holder Muriel
- Holder Susan
- Hollingsworth Georgina
- Homfray Tessa
- Humphreys Mervyn
- Hurles Matthew E.
- Hurst Jane
- Hutton Ben
- Ingram Stuart
- Irving Melita
- Islam Lily
- Jackson Andrew
- Jarvis Joanna
- Jenkins Lucy
- Johnson Diana
- Jones Elizabeth
- Jones Philip
- Jones Wendy D.
- Josifova Dragana
- Joss Shelagh
- Kaemba Beckie
- Kaplanis Joanna
- Kazembe Sandra
- Kelsell Rosemary
- Kerr Bronwyn
- King Daniel
- Kingston Helen
- Kini Usha
- Kinning Esther
- Kirby Gail
- Kirk Claire
- Kivuva Emma
- Kraus Alison
- Krishnappa Netravathi
- Kumar Dhavendra
- Kumar V. K. Ajith
- Lachlan Katherine
- Lam Wayne
- Lampe Anne
- Langman Caroline
- Lees Melissa
- Lim Derek
- Longman Cheryl
- Lowther Gordon
- Lynch Sally A.
- Magee Alex
- Maher Eddy
- Male Alison
- Mansour Sahar
- Marks Karen
- Martin Katherine
- Mason Laura E.
- Maye Una
- McCann Emma
- McConnell Vivienne
- McEntagart Meriel
- McGowan Ruth
- McKay Kirsten
- McKee Shane
- McMullan Dominic J.
- McNerlan Susan
- McRae Jeremy F.
- McWilliam Catherine
- Mehta Sarju
- Metcalfe Kay
- Middleton Anna
- Miedzybrodzka Zosia
- Miles Emma
- Mohammed Shehla
- Montgomery Tara
- Moore David
- Morgan Sian
- Morton Jenny
- Mugalaasi Hood
- Murday Victoria
- Murphy Helen
- Naik Swati
- Nellåker Chris
- Nemeth Andrea
- Nevitt Louise
- Newbury-Ecob Ruth
- Norman Andrew
- O'Shea Rosie
- Ogilvie Caroline
- Ong Kai-Ren
- Park Soo-Mi
- Parker Michael
- Parker Michael J.
- Patel Chirag
- Paterson Joan
- Payne Stewart
- Perrett Daniel
- Phipps Julie
- Pilz Daniela T.
- Pollard Martin
- Pottinger Caroline
- Poulton Joanna
- Pratt Norman
- Prescott Katrina
- Price Sue
- Pridham Abigail
- Prigmore Elena
- Procter Annie
- Purnell Hellen
- Quarrell Oliver
- Ragge Nicola
- Rahbari Raheleh
- Rajan Diana
- Randall Josh
- Rankin Julia
- Raymond Lucy
- Rice Debbie
- Robert Leema
- Roberts Eileen
- Roberts Gillian
- Roberts Jonathan
- Roberts Paul
- Ross Alison
- Rosser Elisabeth
- Saggar Anand
- Samant Shalaka
- Sampson Julian
- Sandford Richard
- Sarkar Ajoy
- Schweiger Susann
- Scott Richard
- Scurr Ingrid
- Selby Ann
- Seller Anneke
- Sequeira Cheryl
- Shannon Nora
- Sharif Saba
- Shaw-Smith Charles
- Shearing Emma
- Shears Debbie
- Sheridan Eamonn
- Sifrim Alejandro
- Simonic Ingrid
- Singh Tarjinder
- Singzon Roldan
- Skitt Zara
- Smith Audrey
- Smith Kath
- Smithson Sarah
- Sneddon Linda
- Splitt Miranda
- Squires Miranda
- Stewart Fiona
- Stewart Helen
- Straub Volker
- Suri Mohnish
- Sutton Vivienne
- Swaminathan Ganesh Jawahar
- Sweeney Elizabeth
- Tatton-Brown Kate
- Taylor Cat
- Taylor Rohan
- Tein Mark
- Temple I. Karen
- Thomson Jenny
- Tischkowitz Marc
- Tivey Adrian R.
- Tomkins Susan
- Torokwa Audrey
- Treacy Becky
- Turner Claire
- Turnpenny Peter
- Tysoe Carolyn
- Vandersteen Anthony
- Varghese Vinod
- Vasudevan Pradeep
- Vijayarangakannan Parthiban
- Vogt Julie
- Wakeling Emma
- Wallwark Sarah
- Waters Jonathon
- Weber Astrid
- Wellesley Diana
- Whiteford Margo
- Widaa Sara
- Wilcox Sarah
- Wilkinson Emily
- Williams Denise
- Williams Nicola
- Wilson Louise
- Woods Geoff
- Wragg Christopher
- Wright Caroline F.
- Wright Michael
- Yates Laura
- Yau Michael
- Publication venue
- Nature
- Publication date
- 24/01/2017
- Field of study
The genomes of individuals with severe, undiagnosed developmental disorders are enriched in damaging de novo mutations (DNMs) in developmentally important genes. Here we have sequenced the exomes of 4,293 families containing individuals with developmental disorders, and meta-analysed these data with data from another 3,287 individuals with similar disorders. We show that the most important factors influencing the diagnostic yield of DNMs are the sex of the affected individual, the relatedness of their parents, whether close relatives are affected and the parental ages. We identified 94 genes enriched in damaging DNMs, including 14 that previously lacked compelling evidence of involvement in developmental disorders. We have also characterized the phenotypic diversity among these disorders. We estimate that 42% of our cohort carry pathogenic DNMs in coding sequences; approximately half of these DNMs disrupt gene function and the remainder result in altered protein function. We estimate that developmental disorders caused by DNMs have an average prevalence of 1 in 213 to 1 in 448 births, depending on parental age. Given current global demographics, this equates to almost 400,000 children born per year
Effects of antiplatelet therapy after stroke due to intracerebral haemorrhage (RESTART): a 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
- 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
- Birchall Kathryn
- Birns Jonathan
- Black Toby
- Blades Alex
- Blair Caroline
- Blair Caroline
- Blair Gordon
- Blane Sujata
- Blank Catrin
- Blight Adrian
- Board Joanne
- Board Sarah
- Bokhari Maria
- Bond Kirsty
- Bowring Angela
- Boxall Cherish
- Breeds Joanna
- Brew Helen
- Brezitski Maria
- Bridger Hayley
- Brodie Fiona
- Brotherton Lucy
- Broughton David
- Brown Claire
- Brown Ellen
- Brown Pauline
- Brown Sarah
- Bruce David
- Buchanan David
- Buck Amanda
- Buckle Steve
- Buckle Steve
- Buckley Clare
- Bunea George
- Burger Ilse
- Burgess Laura
- Burgess Seona
- Burssens Evelyne
- Butler Adrian
- Butler Donna
- Butler Rebecca
- Butterworth-Cowin Nicola
- Button Denise
- Buxton Jean
- Byrne Anthony
- Cageao Julie
- Caine Sarah
- Campbell Robert
- Carpenter Michael
- Carpio Racquel
- Carrie Johanna
- Cassidy Tim
- Causley Chelsea
- Chadbourn Indra
- Chadha Dinesh
- Chamberlain Angela
- Chan Kelly
- Chandrakumar Aberami
- Chapman Kath
- Chapman Nicola
- Charles Bethan
- Chatterjee Kausic
- Chaudhry Afnan
- Chauhan Meena
- Chenna Srikanth
- Cherian Suja
- Cheripelli Bharath Kumar
- Chopra Neha
- Choulerton James
- Choy Lillian
- Clarke Brian
- Clarke Caroline
- Clarke Judith
- Clarke Natasha
- Clarke Rebecca
- Clarke Samantha
- Clarkson Emma
- Clay Caroline
- Clayton Susan
- Clayton-Evans Lisa
- Cluckie Gillian
- Cochrane Helen
- Codd Laura
- Cohen David
- Collins Kayleigh
- Connor Lynda
- Constantin Carmen
- Cook Angela
- Cooper Martin
- Copeland Claire
- Cosier Tracey
- Courtauld Gillian
- Couser Mandy
- Coward Lucy
- Cowie Linda
- Cox Chantel
- Cox Chloe
- Cox Penelope
- Crabtree Karen
- Crawford Pam
- Crawford Susan
- Creeden Robyn
- Crisp Sarah
- Cronin Julie
- Crook Luci
- Crosbie Caroline
- Crouch Nichola
- Crown Rachel
- Crowther Hannah
- Cuddy Sarah
- Cuenoud Larissa
- Cullen Claire
- Culmsee Charlotte
- Cunningham James
- Cunningham Mishell
- Cvoro Vera
- Dacey Lynne
- Dakin Katy
- Dallol Bander
- Dangri Puneet
- Datta Prabal
- Davey Richard
- David Anette
- David Owen
- Davies Caroline
- Davies Ruth
- Davies Silvie
- Davis Fiona
- Davis Michelle
- Day Nicola
- Dayal Nilofer
- De Berker Henry
- Deary Ann
- Denic Hayley
- Dennis MS
- Denniss Carol
- Devine Joseph
- Devitt Nicola
- Dewar Richard
- Dhakal Mahesh
- Dhar Saikat
- Dickinson Christina
- Dickson Christine
- Dima Sofia
- Dinsmore Lynn
- Dixon Lynn
- Dobson Tracey
- Dodd Angela
- Dodd Emily
- Doherty Mandy
- Doherty Mandy
- Donaldson Denise
- Donnelly Richard
- Doubal Fergus
- Dow Lindsey
- Downham Susan
- Doyle Clare
- Doyle Donna
- Drever Jonathan
- du Plessis Johannes
- Dube Judith
- Duberley Stephen
- Dunn Linda
- Dunne Karen
- Durairaj Ramesh
- Durman Helen
- Dutta Dipankar
- Dynan Kevin
- Edwards Mandy
- Egerton Shuna
- Eglinton Charlotte
- Eglinton Charlotte
- El Tawil Salwa
- Elfandi Khaled
- Elliot Jennifer
- Elliott Emma
- Ellis Sam
- Emberson Jonathan
- Emsley Hedley
- England Timothy
- Epstein Daniel
- Erande Renuka
- Erumere Esther
- Esisi Bernard
- Esisi Bernard
- Esson Derek
- Esson Derek
- Evans Rachel
- Evans Sue
- Eveson David
- Ewing Jordan
- Fathima Razik
- Fawcett Michelle
- Feerick Shez
- Fennelly Ruth
- Ferdinand Phillip
- Findlay Paul
- Finlay Sarah
- Finney Kay
- Fitzell Pauline
- Fitzsimmons Paul
- Fletcher Glyn
- Fletcher Jo
- Fong Rosanna
- Foot Jayne
- Foote Leanne
- Ford Gary
- Foster Eliza
- Fotherby Ken
- Fox Charlotte
- Francia Nina
- Francis Jobbin
- Fraser Ruth
- Fraser Ruth
- Fuller Tracy
- Fulton Ailsa
- Furnace Jacqueline
- Gadapa Naveen
- Gainard Glyn
- Gainsborough Nicola
- Gallagher Jill
- Gallagher Louise
- Gallifent Rachel
- Gamble Ed
- Garcia Tatiana
- Gardener Léjeune
- Garfield-Smith Joanne
- Garside Mark
- Gartrell Imogen
- Gascoyne Rachel
- Gattringer Thomas
- Gautam Nikki
- Gaylard Jane
- Gbadamoshi Lukuman
- Geraghty Olivia
- Ghaly George
- Ghatala Rita
- Ghosh Sandip
- Giallombardo Elio
- Gilham Ellie
- Gilmour Danielle
- Gilzeane Nicola
- Glass Jon
- Gleave Laura
- Glover Rachel
- Godfrey Margi
- Goff Anita
- Goorah Neetish
- Gott Valerie
- Gow Heather
- Graham Carol
- Graham Ruth
- Gray Jane
- Green Carole
- Greenwood Richard
- Gregory Bindu
- Greig Jill
- Grimwood Gemma
- Grocott Jeanette
- Grue Rebecca
- Gulliver Diane
- Guo Fenglin
- Gupwell Karin
- Guthrie Lucy Belle
- Guy Helen
- Guyler Paul
- Hague Adam
- Haider Syed
- Hairsine Brigid
- Hakim Eluzai
- Hall Andrea
- Halse Omid
- Handley Dominic
- Hann Gail
- Hannon Niamh
- Hansen Christian
- Haque Mohammad
- Hardwick Anne
- Harkness Kirsty
- Harrington Frances
- Harrington-Davies Yasmin
- Harrison Louise
- Harrison Melanie
- Harrison Thomas
- Harston George
- Harvey Kirsten
- Harvey Miriam
- Hassan Ahamad
- Hassan Hardi
- Havard Diane
- Hayes Anne
- Hayhoe Helen
- Hayman Rachel
- Hays Carole
- Hazel Beth
- Hedstrom Amanda
- Hedstrom Amanda
- Hemsley Anthony
- Henry Margo
- Herman Jane
- Hervey Simon
- Hewitt Jonathan
- Hiden Joanne
- Hogan Caroline
- Hogg Valerie
- Holden Melinda
- Holmes Clare
- Homan Jane
- Hooley Michaela
- Horan Kathleen
- Horton Sarah
- Hostettler Isabel
- Hove Dionne
- Howaniec Laura
- Howard Gabriella
- Howard Joanne
- Howard Peter
- Howcroft Deborah
- Howe Jo
- Huang Xuya
- Huggett Isabel
- Hughes Chloe
- Hughes Claire
- Hughes Tom
- Humphreys Louise
- Humphries Fiona
- Hunt Benjamin
- Hunt Nicholas
- Hunter Annemarie
- Hunter Neil
- Hurford Frances
- Hurley Jennifer
- Hussain Malik
- Hutchison Aidan
- Hyams Benjamin
- Hyatt Lisa
- Imam Javed
- Ingham Andrea
- Ingram Tanya
- Innes Karen
- Iqbal Arshi
- Iqbal Mohammad Shahzad
- Irvine Janice
- Ispoglou Sissy
- Ivatts Simone
- Jackson Benjamin
- Jackson Linda
- Jagger Jenny
- Jagpal Baljit
- James Ali
- James Claire
- James Martin
- Jarapa Rowilson
- Jarrett David
- Jeffs Carol
- Jelley Benjamin
- Jenkins Colin
- Jennings-Preece Karla
- Jeyaraj Naomi
- Jha Ratneshwari
- Jinks Emma
- Johnes Mary
- Johnson Sharon
- Jones Ifan
- Jones Ifan
- Jones Kirsty
- Jones Rachael
- Jones Stephanie
- Jones Terry
- Jones Val
- Jordan Carla
- Jose Deepa
- Jose Josin
- Joshi Yogish
- Joyson Anu
- Jupp Becky
- Justin Frances
- Kakar Puneet
- Kalathil Latheef
- Kalladka Dheeraj
- Kamara Christine
- Kambafwile Mary
- Kane Ingrid
- Kar Arindam
- Keegan Breffni
- Keeling Elizabeth
- Keenan Samantha
- Kelavkar Shyam
- Kelly Christine
- Kelly Debs
- Kelly Jim
- Kelly Siobhan
- Keltos Marketa
- Kennedy James
- Kennedy Kate
- Kenton Antony
- Kerin Lourda
- Kerr Enda
- Kerr Gillian
- Keshvara Rekha
- Khan Mohammad
- Khan Shagufta
- Khan Usman
- Khan Uzma
- Kibutu Faith
- King Sam
- Kingwell Hayley
- Kini Manohar
- Klaasen Katrina
- Knops Kerstin
- Krishnamoorthy Shrivakumar
- Krishnamurthy Ramesh
- Krishnamurthy Vinodh
- Krishnan Kailash
- Krishnan Manju
- Krommyda Magdalini
- Kullane Sagal
- Kumar Balakrishna
- Kumar Pradeep
- Kunhunny Swapna
- Lam Man Yee
- Lambert Caroline
- Landers Geraldine
- Langhorne Peter
- Lasserson Daniel
- Latter Laura
- Law Zhe
- Lawrence Tara
- Lawson Heidi
- Leason Sandra
- Lee Stephanie
- Leggett Jacqui
- Lenti Giulia
- Lerpiniere Christine
- Lerpiniere Christine
- Licenik Radim
- Lindert Ralf
- Little Victoria
- Littleton Edward
- Ljubez Anja
- Loganathan Thayalini
- Longland Barbara
- Lopez Paula
- Lovelock Caroline
- Lowe Gordon
- Lucas Linda
- Lucas Suzanne
- Luder Robert
- Lyjko Sue
- Maanoosi Mehran
- Maatouk Ahmad
- Macaden Ashish
- MacInnes Brian
- MacLennan Beverly
- MacLeod Mary
- Macleod MR
- MacLiver Linda
- MacRaild Allan
- Maddula Mohana
- Madigan Barbara
- Maguire Holly
- Maguire Stuart
- Maiden Susan
- Majis Arshad
- Majmudar Nikhil
- Makawa Linetty
- Mangion David
- Manning Lisa
- Manoj Aravind
- Mardania Rina
- Marigold James Richard
- Markova Skarlet
- Marks Katherine
- Marsden Tracy
- Marshall Sally
- Martin Irene
- Mashate Sheila
- Mason Cathy
- Mate Abhijit
- Mathieson Philip
- Matias Oliver
- Matthews Christopher
- Maund Bev
- McAlpine Christine
- McArdle Damian
- Mcauley Sean
- McCann Stephanie
- McCarron Mark
- McClelland Beverley
- McCormick Katrina
- McCormick Katrina
- McDonald Shanni
- 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
- Miriam Skelton
- Mistri Amit
- Mitchell Jennifer
- Mitra Dipayan
- Mohammed Niaz
- Mohd Nor Azlisham
- Mokoena Betty
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- Wynter Inez
- Yadava Rajendra
- Yip Brigitte
- Young Andrew
- Zachariah George
- Zahoor Tajammal
- Zoe Mellor
- Publication venue
- 'Elsevier BV'
- Publication date
- 29/06/2019
- Field of study
Background:
Antiplatelet therapy reduces the risk of major vascular events for people with occlusive vascular disease, although it might increase the risk of intracranial haemorrhage. Patients surviving the commonest subtype of intracranial haemorrhage, intracerebral haemorrhage, are at risk of both haemorrhagic and occlusive vascular events, but whether antiplatelet therapy can be used safely is unclear. We aimed to estimate the relative and absolute effects of antiplatelet therapy on recurrent intracerebral haemorrhage and whether this risk might exceed any reduction of occlusive vascular events.
Methods:
The REstart or STop Antithrombotics Randomised Trial (RESTART) was a prospective, randomised, open-label, blinded endpoint, parallel-group trial at 122 hospitals in the UK. We recruited adults (≥18 years) who were taking antithrombotic (antiplatelet or anticoagulant) therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage, discontinued antithrombotic therapy, and survived for 24 h. Computerised randomisation incorporating minimisation allocated participants (1:1) to start or avoid antiplatelet therapy. We followed participants for the primary outcome (recurrent symptomatic intracerebral haemorrhage) for up to 5 years. We analysed data from all randomised participants using Cox proportional hazards regression, adjusted for minimisation covariates. This trial is registered with ISRCTN (number ISRCTN71907627).
Findings:
Between May 22, 2013, and May 31, 2018, 537 participants were recruited a median of 76 days (IQR 29–146) after intracerebral haemorrhage onset: 268 were assigned to start and 269 (one withdrew) to avoid antiplatelet therapy. Participants were followed for a median of 2·0 years (IQR [1·0– 3·0]; completeness 99·3%). 12 (4%) of 268 participants allocated to antiplatelet therapy had recurrence of intracerebral haemorrhage compared with 23 (9%) of 268 participants allocated to avoid antiplatelet therapy (adjusted hazard ratio 0·51 [95% CI 0·25–1·03]; p=0·060). 18 (7%) participants allocated to antiplatelet therapy experienced major haemorrhagic events compared with 25 (9%) participants allocated to avoid antiplatelet therapy (0·71 [0·39–1·30]; p=0·27), and 39 [15%] participants allocated to antiplatelet therapy had major occlusive vascular events compared with 38 [14%] allocated to avoid antiplatelet therapy (1·02 [0·65–1·60]; p=0·92).
Interpretation:
These results exclude all but a very modest increase in the risk of recurrent intracerebral haemorrhage with antiplatelet therapy for patients on antithrombotic therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage. The risk of recurrent intracerebral haemorrhage is probably too small to exceed the established benefits of antiplatelet therapy for secondary prevention
Effects of antiplatelet therapy after stroke due to intracerebral haemorrhage (RESTART): a 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
- 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
- Birchall Kathryn
- Birns Jonathan
- Black Toby
- Blades Alex
- Blair Caroline
- Blair Caroline
- Blair Gordon
- Blane Sujata
- Blank Catrin
- Blight Adrian
- Board Joanne
- Board Sarah
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- Chandrakumar Aberami
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- Murali Elodie
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- Parakramawansha Ruwan
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- Peixoto Cassilda
- Penge Justin
- Perez Jane
- Perfitt Rebekah
- Perkins Charlotte
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- Perry Jack
- Persad Nicola
- Peters Jenny
- Pettitt Kerry
- Phiri Duke
- Pitt-Ford Alexandra
- Pitt-Kerby Tressy
- Plewa Catherine
- Poku Philip
- Ponnambath Suheil
- Poultney Una
- Pound Susan
- Power Michael
- Pressly Vanessa
- Price Fiona
- Proeschel Harald
- Punekar Shuja
- Punter Martin
- Pusalkar Aparna
- Putterill Janet
- Quinn Leanne
- Quinn Outi
- Qureshi Sammie
- Ragab Suzanne
- Raghunathan Senthil
- Rahman Bithi
- Rai Baljinder
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- Ramachandran Sankaranarayana
- Ramadan Hawraman
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- Reddan Julie
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- Redgrave Jessica
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- Richards Emma
- Rinkel Gabriel
- Roberts Josh
- Robinson Matthew
- Robinson Naomi
- Rodgers Alicia
- 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 PAG
- 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 N
- Srinivasan Meena
- Stafford Samantha
- Stafford Samantha
- Stanners Andrew
- Steele Amy
- Stephen J
- Stephens Claire
- Stevens Angela
- Stevens Stephanie
- Stevenson Sarah
- Stewart Kelvin
- Stocks Kathy
- Stone Andrew
- Storton Sharon
- Strain David
- Subramonian Santhosh
- Sudlow CLM
- Sukdeo Varthi
- Sullivan Frank
- Sultan Sulaiman
- Suttling Anne
- Sutton Claire
- Sutton Patrick
- Sutton Victoria
- Sword Jane
- Sykes Lucy
- Symonds Stuart
- Szabo Susan
- Tallantyre Emma
- Tanate Alfonso
- Tandy Jane
- Tate Margaret
- Tauro Suzanne
- Tayler Michelle
- Taylor Pat
- Taylor Vicky
- Teal Rachel
- 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 JM
- 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 DJ
- Whitcher Alison
- White James
- White Julie
- White PM
- White Susan
- Whiteley WN
- 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
- 29/06/2019
- Field of study
Background:
Antiplatelet therapy reduces the risk of major vascular events for people with occlusive vascular disease, although it might increase the risk of intracranial haemorrhage. Patients surviving the commonest subtype of intracranial haemorrhage, intracerebral haemorrhage, are at risk of both haemorrhagic and occlusive vascular events, but whether antiplatelet therapy can be used safely is unclear. We aimed to estimate the relative and absolute effects of antiplatelet therapy on recurrent intracerebral haemorrhage and whether this risk might exceed any reduction of occlusive vascular events.
Methods:
The REstart or STop Antithrombotics Randomised Trial (RESTART) was a prospective, randomised, open-label, blinded endpoint, parallel-group trial at 122 hospitals in the UK. We recruited adults (≥18 years) who were taking antithrombotic (antiplatelet or anticoagulant) therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage, discontinued antithrombotic therapy, and survived for 24 h. Computerised randomisation incorporating minimisation allocated participants (1:1) to start or avoid antiplatelet therapy. We followed participants for the primary outcome (recurrent symptomatic intracerebral haemorrhage) for up to 5 years. We analysed data from all randomised participants using Cox proportional hazards regression, adjusted for minimisation covariates. This trial is registered with ISRCTN (number ISRCTN71907627).
Findings:
Between May 22, 2013, and May 31, 2018, 537 participants were recruited a median of 76 days (IQR 29–146) after intracerebral haemorrhage onset: 268 were assigned to start and 269 (one withdrew) to avoid antiplatelet therapy. Participants were followed for a median of 2·0 years (IQR [1·0– 3·0]; completeness 99·3%). 12 (4%) of 268 participants allocated to antiplatelet therapy had recurrence of intracerebral haemorrhage compared with 23 (9%) of 268 participants allocated to avoid antiplatelet therapy (adjusted hazard ratio 0·51 [95% CI 0·25–1·03]; p=0·060). 18 (7%) participants allocated to antiplatelet therapy experienced major haemorrhagic events compared with 25 (9%) participants allocated to avoid antiplatelet therapy (0·71 [0·39–1·30]; p=0·27), and 39 [15%] participants allocated to antiplatelet therapy had major occlusive vascular events compared with 38 [14%] allocated to avoid antiplatelet therapy (1·02 [0·65–1·60]; p=0·92).
Interpretation:
These results exclude all but a very modest increase in the risk of recurrent intracerebral haemorrhage with antiplatelet therapy for patients on antithrombotic therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage. The risk of recurrent intracerebral haemorrhage is probably too small to exceed the established benefits of antiplatelet therapy for secondary prevention
Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans
- Author
- Abbasi Z
- Abdul-Hamid M Akhlil
- Abel Paul D
- Abrams Paul H
- Adab Fawzi A
- Adamson Andrew
- Adeyoju A
- Adolfson Jan
- Afzal Naveed
- Ahiaku Ernest K N
- Ahmed Munir
- Al Sudani Mohammed L
- Al-Samarraie Amir S M
- Al-Samerraie [Unknown]
- Al-Singary Waleed
- Al-Sudani [Unknown]
- Alcock Christopher
- Alexander Kimberly
- Ali Zulfiqar
- Almond David J
- Alonzi Roberto
- Aly Markus
- Amin Al Olama Ali
- Anderson John
- Andrews Henry
- Andrews Steven
- Anjum Iqbal
- Anson Ken
- Anyamene Nicola A
- Apakama Ike
- Aparcia F
- Archbold J A A
- Arndt Volker
- Ash D
- Ashford Richard F U
- Auvinen Anssi
- Azzabi A
- Badenoch David
- Bahl Amit
- Bailey Karen
- Bailey M J
- Ball Andrew J
- Banerjee G
- Barber Jim
- Barber N
- Baria [Unknown]
- Barnes Douglas G
- Barros-Silva Joao
- Barwell Julian
- Bashir J
- Basu Pradip
- Bates Christopher A
- Batra Jyotsna
- Bax N A
- Baxter-Smith D
- Bdesha Amar
- Beacock Christopher J M
- Beaney Ronald P
- Beard Ralph
- Beatty John D
- Beck Rupert
- Beese Gail
- Beesley Sharon
- Bell C Richard W
- Bellringer James
- Benlloch Garcia Sara
- Benson Richard
- Beresford [Unknown]
- Bevis Christopher R A
- Bhana Rajanee
- Bhanot S
- Bhatnagar A
- Bhatt R I
- Birch Brian
- Birtle Alison
- Bishop M
- Biyani C Shekhar
- Blacklock A R E
- Blades Rosemary
- Bliss Peter
- Bloomfield David J
- Boddy S
- Bollina Prasad
- Bonnington Sue
- Booth C M
- Bose Pradeep
- Bott Michael C
- Bottomley David
- Boucher Nigel R
- Bowen J
- Bower Mark
- Bowsher W G
- Boyd P J R
- Bradshaw Lynne
- Bramble F James
- Brenner Hermann
- Brewster Simon F
- Briggs Tim
- Brock Cathryn
- Brock Sue
- Bromage Stephen
- Broms Michael
- Brough Richard
- Brown Andrew A
- Brown Paul
- Brown Paul M
- Brown Richard
- Brown Stephen
- Browning Tony J
- Bryan N
- Burgess Neil A
- Burns-Cox Nicholas
- Butterbach Katja
- Butterworth Paul C
- Cahill D
- Callaghan P S
- Calleary John
- Calleja M
- Calman Frances
- Camilleri Philip
- Campbell Alister
- Cannon Andrea
- Cannon-Albright Lisa
- Carnell Dawn M
- Carr T W
- Carter Adam C
- Carter Charles J M
- Carter Simon
- Castle Bruce M
- Catto James
- Cavalli-Bjoerkman Carin
- Chadwick David
- Chahal Rohit
- Chakraborti P
- Chappell [Unknown]
- Charig C
- Chetiyawardana Anula D
- Chilton Christopher
- Chinegwundoh F I
- Chong Irene
- Choudhury Ananya
- Chow Wai-Man
- Christmas Timothy J
- Christova Svetlana
- Churn Mark J
- Cieza-Borrella Clara
- Clarke Noel W
- Clavijo-Eisele Jorge
- Clements Judith A
- Coe M
- Coetzee Gerhard A
- Cohen N P
- Coker C
- Cole David J
- Cole O
- Cole Trevor
- Collins Angus
- Collins Gerald
- Collinson Matthew
- Conn I
- Connell C
- Conti David V
- Cook Audrey
- Cook Margaret
- Cooke Peter
- Cooksey Graeme
- Coombs L
- Cooper Debbie
- Copland Robert F
- Cornaby Andrew J
- Cornford P A
- Corolis [Unknown]
- Corr John
- Costello C B
- Coull Mrs N
- Cowan Richard
- Cox Angela
- Cox Robert
- Coyle C
- Crew Jeremy
- Crisp John C
- Cross W
- Cruger Dorthe
- Crundwell Malcolm
- Cummings [Unknown]
- Cybulski Cezary
- Dadaev Tokhir
- Dahar Nazeer
- Daniel Francis N
- Darrad J
- Daruwala Pallon
- Das Gautam
- Datta Shibendra
- Davidson S
- Davies Joseph
- Davis Michael
- Davison Owen W
- Dawkins Guy
- Dawson Chris
- De Bolla Alan R
- Dearnaley David
- Desai Ken M
- Deutsch George P
- Dick John
- Dickinson Andrew J
- Dickson Jeanette
- Dikov Tihomir
- Dinneen Michael
- Dixit Sanjay
- Dobbs H Jane
- Doble A
- Doble Andrew
- Dodds David
- Doherty Alan
- Donaldson P
- Donovan Jenny L
- Dooldeniya M
- Douglas S Fiona
- Down Liz
- Drake [Unknown]
- Duchesne Gill M
- Duffy Peter
- Dunn Michael
- Dunsmuir W D
- Durkan Garrett
- Durrani Sajid K
- Easton Douglas
- Eaton Alan C
- Eccles Diane
- Eckert Allison
- Eddy B
- Eden C D
- Edwards J
- Eeles Rosalind A
- El-Modir A
- Elkabir Jeremy
- Elliott Emma
- Elliott P Tony
- Ellis B W
- Ellis R
- Elves Andrew W S
- Elwell Christine
- Emberton Mark
- Emmerson Louise
- England Roland C D
- Errington R D
- Evans D Gareth
- Falconer Alison
- Fawcett Derek
- Featherston C
- Featherstone Carolyn J
- Feggetter Jeremy
- Ferguson C
- Fermont D
- Ferro Michael
- Fisher Cyril
- Fitzgerald Liesel
- Fitzgerlad Liesel M
- Fletcher Matthew
- Folkes A
- Ford Trevor F
- Foster Paul W
- Franks Kevin N
- Freedman Mathew
- Frim Olivera
- Gale Joanna
- Gallegos Christopher
- Gelister James S
- George Anne
- Ghana [Unknown]
- Gibbs Stephanie
- Gilbert Hugh
- Giles Graham G
- Gillatt David
- Glaholm John
- Glass Jonathan M
- Glenister James
- Goode Thomas D
- Gordon E M
- Govindasami Koveela
- Gower Richard L
- Graham John
- Green Damian
- Greenland Jonathan
- Grieve Robert
- Griffiths Thomas R L
- Gronberg Henrik
- Gujral Sandy
- Gupta Nishi
- Gurun Riza Murat
- Gustafsson Sven
- Guy Michelle
- Guy Peter J
- Haiman Christopher A
- Haldar Neil
- Halder N
- Haley James
- Hamdy F C
- Hamdy Freddie
- Hamilton C
- Hammonds John
- Hampson S J
- Hanbury Damien C
- Hardman P D John
- Harland Stephen J
- Harney John M
- Harper Peter
- Harris D
- Harris Sarah
- Harrison G S M
- Harriss D R
- Harvey-Hills N
- Hawkyard Simon
- Hazel Steve
- Hazelett Dennis J
- Heath Catherine M
- Heathcote Peter
- Hehir Michael
- Hellawell Giles O
- Henderson Brian E
- Hendry David
- Henley Mike
- Henrique Rui
- Henry Ann
- Herbert Pippa
- Herkommer Kathleen
- Hetherington John
- Hickish Tamas
- Hicks James A
- Hilman Serena
- Hindley Richard
- Hindmarsh John R
- Hines John
- Hingorani M
- Ho Edwin T S
- Hodgson Shirley
- Hoffman U
- Holden David
- Holding Peter
- Hollingdale A
- Hollins Graham W
- Holmes Simon A V
- Holt Sarah
- Hopper John L
- Horan Gail
- Horwich Alan
- Hoskin Peter
- Howell Graham P
- Howson Joanne
- Hrouda D
- Huddart Robert
- Hudson Liz
- Hughes Michael
- Hughes Owen
- Hughes Rob
- Humber Caroline
- Iacovou John W
- Ibrahim A
- Inglis John A
- Irving Stuart
- Irwin C
- Iversen Peter
- Izatt Louise
- Izegbu Victor
- Jameel Basharat
- James Michael J
- James N
- James R Lester
- Javle Pradip
- Jenkins P
- Jhavar Sameer
- Johansson Jan-Erik
- Jones Chris R
- Jones David A
- Jones Gareth
- Jones Mandy
- Joseph J
- Joss Shelagh
- Jugurnauth-Little Sara
- Kachakova Darina
- Kaisary Amir
- Kaliski Alexandre L
- Kaneva Radka
- Kapur G
- Karim O
- Karlsson Ami
- Karp Stephen J
- Kedda Mary-Anne
- Keeley F X
- Kelkar Anand R
- Kelleher J P
- Kelly John
- Kenwrick Sue
- Kerr Kris
- Key Tim J
- Khan F
- Khaw Kay-Tee
- Khoo Vincent
- Kibel Adam S
- Kierzek Andrzej
- Kimber Rachel M
- Kinder R
- Kirby Roger S
- Kirk David
- Kirkbride Peter
- Kirollos Magdi M
- Klarskov Peter
- Kluzniak Wojciech
- Kockelbergh Roger
- Koenig Philip C W C
- Kooiman Gordon G
- Koreich O
- Kote-Jarai Zsofia
- Koupparis Anthony
- Kourah Mohamed
- Kraus Sigurd
- Kujala Paula
- Kujawa Magda L
- Kulkarni Ravi
- Kumar M
- Kumar Rajeev
- Kunkler Ian H
- Kynaston H
- Kynaston Howard
- Lachlan Katherine L
- Laing Robert
- Lalloo Fiona
- Lancashire M
- Lane Athene
- Langley Stephen E M
- Laniado Marc
- Larner T R
- Lau Maurice W
- Lawrence W T
- Lawson Anne
- Le Roux Pieter J
- Leader Mary
- Lee A
- Lee J O
- Lee L
- Lemburger R John
- Lennon Teresa
- Leone Priscilla
- Leongamornlert Daniel
- Lester Jason
- Leung Hing
- Lewis D Christopher
- Lewis J
- Li Qiuyan
- Lim Hui-Yi
- Lin Hui-Yi
- Liston Thomas
- Livni Naomi
- Livsey Jacqueline
- Lloyd S
- Locke Imogen
- Lodge Richard
- Logue John
- Longmuir Mark
- Lophatananon Artitaya
- Lophatonanon Artitaya
- Lubinski Jan
- Lucas Malcolm G
- Luedeke Manuel
- Luscombe C J
- Lydon Anna
- Lynch Michael
- Lynn Naing N K
- Lyons Norma
- MacDermott James P A
- Macdonagh Ruaraidh P
- Macdonald [Unknown]
- Madaan Sanjeev
- Madhava Kudingila R
- Maeaettaenen Liisa
- Maguire Joseph
- Maher E R
- Mahmood Rana
- Maia Sofia
- Maier Christiane
- Mair Graeme H M
- Malone Greg
- Malone Peter R
- Mangar Stephen A
- Mantle Mark
- Mark I
- Marsden Gemma
- Mason M D
- Mason Malcolm
- Mason Robert
- Matanhelia [Unknown]
- Matenhelia Shyam
- Matthews Philip N
- McAleese J
- McBride Donna
- Mcdonnell Shannon K
- McDonnell Shannon K
- McFarlane Jonathan
- McGrath [Unknown]
- McIlhenny Craig
- McInerney Paul
- McIntosh Gregor
- McKinna F
- McLaren Duncan
- McLarty Esther
- McMenemin Rhona
- McNeill Alan
- McNicholas T A
- Meddings Robert N
- Mee A David
- Melcher Lucinda
- Memon [Unknown]
- Menzes Pravin
- Michael Agnieszka
- Miller Marek
- Mills Robert
- Mitchell S
- Mitev Vanio
- Mithal Natasha
- Mitkova Atanaska
- Mitra Anita
- Mobb Gillian E
- Moffat Leslie E F
- Mokete [Unknown]
- Money-Kyrle Julian
- Montgomery Bruce
- Moody Hilary
- Moody Martin P
- Morgan Angela
- Morley Roland
- Morris Sean B
- Morrison Patrick
- Mort Diana
- Mostafid Amir H
- Motiwala Hanif
- Mufti Gulzar
- Muir Gordon
- Muir Kenneth
- Mumtaz Faiz
- Murphy Michael
- Murray Alexandra
- Murray Keith W
- Murrell Shirley
- Murtola Teemu
- Muthukumar D
- Naerger Harry
- Namasivayam Siva
- Nargund Vinod
- Nawrocki [Unknown]
- Neal David E
- Neilson Donald
- Nethersell A
- Newby Jacqueline C
- Newman Hugh
- Newton R
- Nielsen Sune F
- Nordestgaard Børge G
- O'Boyle P J
- O'Brien J
- O'Brien Tim S
- O'Donnell H
- O'Donoghue E
- O'Donoghue Neil
- O'Reilly P
- O'Rourke J S
- O'Sullivan Joe
- O'Sullivan Patricia
- Oakley Neil
- Ogden Chris
- Ohja Hemant
- Oliver Tim
- Omara Tracy
- Ong Eng K
- Osborn David
- Ostler Peter
- Owen J
- Palfrey Edward
- Panades Miguel
- Panakis Niki
- Pancharatnam M
- Pandha Hardev
- Pantelides Michalakis L
- Panwar U
- Parikh Omi
- Park Hyun
- Park Jong Y
- Parker Chris
- Parker Christopher H
- Parys Bohdan T
- Pascoe Sarah
- Pashayan Nora
- Patel Anup
- Paterson Joan
- Pathack S
- Pati Jhumur
- Patterson Helen
- Pattu [Unknown]
- Paul A
- Paul Alan
- Paulo Paula
- Payne Heather
- Peake David
- Pedersen John
- Pedley I
- Pengelly A
- Peracha Amjad M
- Perry Matthew
- Persad Raj
- Peters John
- Pharoah Paul
- Philp N H
- Philp T
- Pickering Lisa M
- Pigott Katharine
- Pinto Pedro
- Plail R
- Plowman P Nicholas
- Pocock Richard D
- Pope A J
- Popert Rick
- Popov Elenko
- Porter Tim
- Potter John M
- Pow-Sang Julio
- Powell Christopher
- Powell Philip
- Powles Thomas B
- Prasad Krishna
- Prasad Seshadri Sri
- Prejbisz J W
- Prescott Stephen
- Protheroe Andrew
- Qureshi Khaver N
- Raby Nigel
- Radlein Selina
- Ragavan Narasimhan
- Raju Palaniappa G S
- Ramachandra Prakash B
- Raman R
- Rane Abhay
- Rankin Julia
- Rao Y
- Ratan Hari L
- Ravi Ramachandran
- Ravishankar K
- Read [Unknown]
- Reddy Paul J
- Rimington Peter R
- Rinckleb Antje
- Rincon Maria
- Riska Shaun
- Ritchie Peter A
- Roberts J Trevor
- Robertson Andrew
- Robinson Angus
- Robinson Anne C
- Robinson Lee Q
- Rochester Mark A
- Roder Andreas
- Rogers P B
- Rosario Derek
- Rosenbaum Tomas P
- Rothwell Neil
- Rowbotham Carl
- Rowe [Unknown]
- Rowley Kathryn
- Ruddy Deborah
- Rundle John
- Russell John M
- Ryan P G
- Sabharwal A
- Saggar Anand K
- Samanci Ali
- Sangar Vijay K
- Santos Joana
- Saunders Edward J
- Saunders Pamela
- Sawyer Emma J
- Saxby M F
- Schaid Daniel J
- Schleutker Johanna
- Schumacher Fredrick
- Schwaibold Hartwig
- Scoble John E
- Scrase Christopher
- Selim [Unknown]
- Sellers Thomas
- Sells Henry
- Sethia Krishna K
- Severi Gianluca
- Shackley David C
- Shaffer [Unknown]
- Shah Nihil
- Shakespeare D
- Shanley Sue
- Sharma Neerah K
- Sheehan Denise J
- Sherwin Elizabeth
- Shum Poh Lin
- Side Lucy
- Sidek Norma
- Signorello Lisa B
- Sikora Karol
- Simcock R
- Sinclair Andrew M
- Singh Pravin
- Siva M
- Slavov Chavdar
- Smith James
- Smith Michael F
- Sokal Michael
- Sole Graham M
- Southey Melissa C
- Speakman Mark J
- Spiers Alexander
- Spurdle Amanda
- Sreenivasan Thiagarajan
- Srihari Narayanan N
- Srinivasan [Unknown]
- Sriram Rajagopalan
- Staffurth John N
- Stanford Janet L
- Stattin Paer
- Stegmaier Christa
- Stephens Sarah
- Stewart D
- Stockdale Andrew
- Stott Mark A
- Stower M J
- Strachan John R
- Stuart Nicholas S A
- Sugden Elaine
- Summerton Duncan
- Sundar Santhanam
- Sundaram S K
- Suresh Gokarakonda
- Susnerwala Shabbir
- Swami Kuchibhotla S
- Symons Stephanie J
- Syndikus Isabel
- Taari Kimmo
- Tahir Saad
- Tammela Teuvo L
- Tammela Teuvo L J
- Tanquay J
- Taylor J W
- Taylor John W
- Teixeira Manuel R
- Terry T
- Thibodeau Stephen N
- Thomas Robert J
- Thomas Stephen A
- Thompson Alan
- Thompson Pauline
- Thomson Alastair H
- Thurston A
- Tidball Sarah
- Tillmans Lori
- Tilsley Owen
- Tindall Stuart F
- Tipples K
- Tong [Unknown]
- Toussi Hamid
- Toy Elizabeth W
- Travis Ruth C
- Trembath Richard C
- Tulloch David N
- Turner Kevin J
- Turner Megan
- Tweedle James
- Tymrakiewicz Malgorzata
- Tyrell C J
- Umez-Eronini N
- Urwin Graeme H
- Vale Justin A
- Van As [Unknown]
- Van As Nicholas
- Vasanthan Subramaniam
- Vesey Sean
- Vilarino-Varela Maria
- Violet John
- Virdi Jaspal
- Viñuela Ana
- Vlahova Aleksandrina
- Vogel Walther
- Wade Robert
- Wahlfors Tiina
- Waite Katherine
- Walker E M
- Walker Roger
- Wallace David M A
- Wallinder Hans
- Wang Liang
- Watkin Nicholas A
- Watson M E
- Waxman J H
- Waymont Brian
- Weaver Andrew
- Webb Ralph J
- Wedderburn Andrew
- Weischer Maren
- Wells Paula
- Wemyss-Holden G D
- Weston P M T
- Wheatley Duncan
- Whelan P
- Whillis D
- Whitmore Ian
- Wiklund Fredrik
- Wilde Adam D
- Wiles Vicki
- Wilkins Marie
- Wilkinson Rosemary
- Williams John H
- Williams Simon
- Willis Michael
- Wills Michael I
- Wilson J R
- Wilson Richard
- Winkler Mathias H
- Wise Marcus
- Wokozorczyk Dominika
- Wokołorczyk Dominika
- Wood Glenn
- Woodhams Simon
- Woodhouse C
- Woodward Cathryn
- Woolf [Unknown]
- Woolfenden K A
- Worlding Jane
- Wright Mark
- Wu Huihai
- WYLIE [Unknown]
- Wylie James P
- Wynne Chris
- Yeadon Trina
- Zachariah Babu
- Zang Angelika
- Zarkar A
- Zheng Wei
- Publication venue
- 'Oxford University Press (OUP)'
- Publication date
- 01/01/2015
- Field of study
Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have
fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in
25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16
regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of
correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP,
while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in
Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium
(LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region.
Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant
enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the
refined data for existing association signals, we estimate that these loci now explain ∼38.9% of the familial relative risk of PrCa,
an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of
PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent
signals within the same regio
Finishing the euchromatic sequence of the human genome
- Author
- . Haifeng
- . Magner
- . Yin
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- Kelley Simon
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- Kettleborough Ross
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- Kosiura Anna
- Kou Zhaohui
- Kovar Christie L.
- Krawczyk Marie-Claude
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- Kremmidiotis Gabriel
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- Kruchowski Scott S.
- Kube Michael
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- Lowenstein Michael G.
- Lowry Stephen
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- MacLean Christine
- Madabhushi Ramki
- Madu Renita C.
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- McLeod Michael P.
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- Meidi Patrick
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- Murayama Yuji
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- Nwokenkwo Stanley
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- Perez Agapito
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- Subramanian Sandhya
- Sudbrak Ralf
- Sugnet Charles W.
- Sulston John
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- Sun Jiajia
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- Sun Min
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- Sun Wei
- Sun Yongqiao
- Sun Yu
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- Sutherland Robert D.
- Sutton Angelica E.
- Svatek Amanda F.
- Svetz Jessica
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- Swainson Chris
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- Swearengen-Shahid Sharhonda
- Sycamore Neil
- Ségurens Béatrice
- Tabor Paul E.
- Tacey Kristina
- Tagett Beckie
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- Takaoka Tori
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- Tamirisa Aparna
- Tan Olivia
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- Tan Xinyu
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- Tansey Jennifer
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- Tatsuyama Miho
- Tatum Owatha I.
- Taudien Stefan
- Taylor Amy
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- Taylor Kate
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- Taylor Tineace R.
- Taylor Todd Duane
- Tchuinga Pierre
- Tee Louise
- Telford Ethan Brett
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- Tesfaye Senait
- Tesmer Judith G.
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- Theil James
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- Thexton David
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- Thomas Ruth
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- Thompson Linda S.
- Thorne Rachel Diane
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- Tian Chaoguang
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- Tice Hope
- Tighe Damon
- Tin-Wollam Aye M.
- Tinsley Emma
- Tochigi Miwako
- Togashi Naoko
- Tomizawa Iori
- Tomlinson Chad
- Tong Jingli
- Topham Kerri
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- Torney David C.
- Totoki Yasushi
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- Trani Lee
- Trankiem Margie
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- Ueland Stephanie
- Ueng Samantha
- Ukegbu Ogechi Nkemdirim
- Ulanovsky Levy E.
- Un Chun
- Ung Quyen
- Upson Darren
- Urban Jeremy B.
- Ureta-Vidal Abel
- Ureta-Vidal Abel
- Usmani Kamran
- Ustaszewska Anna
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- Zhen Zhicheng
- Zheng Haibo
- Zhong Ming
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- 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
Search for a light pseudoscalar Higgs boson in the boosted mu mu tau tau final state in proton-proton collisions at root s=13 TeV
- Author
- Aarrestad Thea Klaeboe
- Aarup Petersen Henriette
- Abbaneo Duccio
- Abbiendi Giovanni
- Abbrescia Marcello
- Abdullin Salavat
- Abercrombie Daniel
- Acharya Himal
- Acosta Darin
- Acosta John Gabriel
- Adam Wolfgang
- Adams Eric
- Adams Mark Raymond
- Adams Todd
- Adloff Catherine
- Adzic Petar
- Agapitos Antonis
- Agarwal Garvita
- Aggleton Robin
- Agram Jean-Laurent
- Aguilar-Benitez Manuel
- Ahmad Ashfaq
- Ahmad Muhammad
- Ahmad Muhammad
- Ahmed Asar
- Ahuja Sudha
- Akbiyik Melike
- Akchurin Nural
- Akgun Bora
- Akpinar Alp
- Albajar Carmen
- Albergo Sebastiano
- Albert Andreas
- Albrow Michael
- Alcaraz Maestre Juan
- Aldaya Martin Maria
- Aldá Júnior Walter Luiz
- Aleksandrov Aleksandar
- Alexakhin Vadim
- Alexander James
- Alhusseini Mohammad
- Alimena Juliette
- Alison John
- Allen Brandon
- Almond John
- Alvarez Gonzalez Barbara
- Alverson George
- Alves Gilvan
- Aly Reham
- Alyari Maral
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- Ambrogi Federico
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- Amin Nick
- Amram Oz
- Amsler Claude
- Anagnostou Georgios
- Anderson Dustin
- Andrea Jeremy
- Andreev Vladimir
- Andreev Yuri
- Andrews Michael Benjamin
- Androsov Konstantin
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- Antunovic Zeljko
- Apanasevich Leonard
- Apollinari Giorgio
- Appelt Eric
- Apresyan Artur
- Apyan Aram
- Araujo Mariana
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- Arcidiacono Roberta
- Arenton Michael Wayne
- Argiro Stefano
- Arneodo Michele
- Asavapibhop Burin
- Asawatangtrakuldee Chayanit
- Asenov Patrick
- Asghar Muhammad Irfan
- Asilar Ece
- Askew Andrew
- Asmuss Paul
- Atakisi Ismail Okan
- Atanasov Ivan
- Ather Mohsan Waseem
- Attikis Alexandros
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- Hoorani Hafeez R
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- Yetkin Elif Asli
- Yi Kai
- Yohay Rachel
- Yoo Hwi Dong
- Yoo Jaehyeok
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- Yu Geum Bong
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- Yuan Li
- Yuan Siqi
- Yuldashev Bekhzod S
- Yumiceva Francisco
- Yusli Mohd Nizam
- Zabi Alexandre
- Zacharopoulou Anna
- Zahid Sema
- Zaleski Shawn
- Zalewski Piotr
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- Zarucki Mateusz
- Zecchinelli Angelo Giacomo
- Zenaiev Oleksandr
- Zenz Seth Conrad
- Zeuner Wolfram Dietrich
- Zghiche Amina
- Zhang Aobo
- Zhang Fengwangdong
- Zhang Huaqiao
- Zhang Jingyu
- Zhang Sijing
- Zhang Wenyu
- Zhang Yi
- Zhang Zhicai
- Zhao Jingzhou
- Zhemchugov Evgenii
- Zhiltsov Victor
- Zhokin Alexander
- Zhu De Hua
- Zhu Ren-Yuan
- Ziemons Tim
- Zientek Margaret
- Zlebcik Radek
- Zobec Joze
- Zoi Irene
- Zolkapli Zukhaimira
- Zorbakir Ibrahim Soner
- Zorbilmez Caglar
- Zotto Pierluigi
- Zou David
- Zucchetta Alberto
- Zumerle Gianni
- Zuo Xunwu
- Zuolo Davide
- Zygala Lara
- Álvarez Fernández Adrian
- Özçelik Özlem
- Publication venue
- Publication date
- 01/01/2020
- Field of study
A search for a light pseudoscalar Higgs boson (a) decaying from the 125 GeV (or a heavier) scalar Higgs boson (H) is performed using the 2016 LHC proton-proton collision data at root s = 13 TeV, corresponding to an integrated luminosity of 35.9 fb(-1), collected by the CMS experiment. The analysis considers gluon fusion and vector boson fusion production of the H, followed by the decay H -> aa -> mu mu tau tau, and considers pseudoscalar masses in the range 3.6 aa -> mu mu tau tau, down to 1.5 (2.0)x10(-4) for m(H) = 125 (300) GeV. Model-dependent limits on B(H -> aa) are set within the context of two Higgs doublets plus singlet models, with the most stringent results obtained for Type-III models. These results extend current LHC searches for heavier a bosons that decay to resolved lepton pairs and provide the first such bounds for an H boson with a mass above 125 GeV.Peer reviewe
Observation of the Production of Three Massive Gauge Bosons at root s=13 TeV
- Author
- Aarrestad Thea Klaeboe
- Aarup Petersen Henriette
- Abbaneo Duccio
- Abbiendi Giovanni
- Abbrescia Marcello
- Abdullin Salavat
- Abercrombie Daniel
- Abu Zeid Shimaa
- Acharya Himal
- Acosta Darin
- Acosta John Gabriel
- Adam Wolfgang
- Adams Eric
- Adams Mark Raymond
- Adams Todd
- Adloff Catherine
- Adzic Petar
- Afanasiev Serguei
- Agapitos Antonis
- Agarwal Garvita
- Aggleton Robin
- Agram Jean-Laurent
- Aguilar-Benitez Manuel
- Ahmad Ashfaq
- Ahmad Muhammad
- Ahmed Asar
- Ahuja Sudha
- Akchurin Nural
- Akgun Bora
- Akpinar Alp
- Albajar Carmen
- Albergo Sebastiano
- Albert Andreas
- Albrow Michael
- Alcaraz Maestre Juan
- Aldaya Martin Maria
- Aldá Júnior Walter Luiz
- Aleksandrov Aleksandar
- Alexander James
- Alhusseini Mohammad
- Alimena Juliette
- Alison John
- Allen Brandon
- Almond John
- Alvarez Gonzalez Barbara
- Alverson George
- Alves Gilvan
- Aly Reham
- Alyari Maral
- Amapane Nicola
- Ambrogi Federico
- Amendola Chiara
- Amin Nick
- Amram Oz
- Amsler Claude
- Anagnostou Georgios
- Anderson Dustin
- Andrea Jeremy
- Andreev Vladimir
- Andreev Yuri
- Andrews Michael Benjamin
- Androsov Konstantin
- Antchev Georgy
- Antunovic Zeljko
- Apanasevich Leonard
- Apollinari Giorgio
- Appelt Eric
- Apresyan Artur
- Apyan Aram
- Araujo Mariana
- Arcaro Daniel
- Arcidiacono Roberta
- Arenton Michael Wayne
- Argiro Stefano
- Arneodo Michele
- Aruta Caterina
- Asavapibhop Burin
- Asawatangtrakuldee Chayanit
- Asenov Patrick
- Asghar Muhammad Irfan
- Asilar Ece
- Askew Andrew
- Asmuss Paul
- Atakisi Ismail Okan
- Atanasov Ivan
- Ather Mohsan Waseem
- Attikis Alexandros
- Auffray Etiennette
- Aushev Tagir
- Auzinger Georg
- Avati Valentina
- Avery Paul
- Avila Carlos
- Awan Muhammad Imran Malik
- Ayala Edy
- Aydogmus Sen Fatma
- Azarkin Maksim
- Azhgirey Igor
- Aziz Tariq
- Azzi Patrizia
- Azzurri Paolo
- Baarmand Marc M.
- Babaev Anton
- Babounikau Illia
- Bacchetta Nicola
- Bachiller Irene
- Bachtis Michail
- Backhaus Malte
- Baden Drew
- Baechler Joachim
- Bagliesi Giuseppe
- Bahinipati Seema
- Baillon Paul
- Bainbridge Robert
- Bakas Georgios
- Bakhshiansohi Hamed
- Baldenegro Barrera Cristian
- Ball Austin
- Ban Yong
- Band Reyer
- Banerjee Sudeshna
- Banerjee Sunanda
- Bansal Sunil
- Barbagli Giuseppe
- Barberis Emanuela
- Bargassa Pedrame
- Baringer Philip
- Barnes Virgil E.
- Barney David
- Baron Owen
- Barrio Luna Mar
- Bartek Rachel
- Bartosik Nazar
- Bartók Márton
- Baselga Marta
- Bastos Diogo
- Battilana Carlo
- Baty Austin
- Bauerdick Lothar A. T.
- Baur Sebastian
- Baxter Samuel
- Bayshev Igor
- Bean Alice
- Beauceron Stephanie
- Beaudette Florian
- Becerril Gonzalez Hugo
- Bechtel Janek
- Beghin Diego
- Behera Prafulla Kumar
- Behera Subash Chandra
- Behnke Olaf
- Bein Samuel
- Belchior Batista Das Chagas Ewerton
- Belforte Stefano
- Bell Ken W.
- Bellan Riccardo
- Belloni Alberto
- Bellora Andrea
- Belyaev Alexander
- Belyaev Andrey
- Benaglia Andrea
- Benato Lisa
- Bencze Gyorgy
- Bendavid Joshua
- Benecke Anna
- Benelli Gabriele
- Beni Noemi
- Benitez Jose F.
- Benussi Luigi
- Beretvas Andrew
- Bergauer Thomas
- Berger Pirmin
- Berger Thomas
- Beri Suman Bala
- Bermúdez Martínez Armando
- Bernardes Cesar Augusto
- Bernet Colin
- Berry Douglas
- Berryhill Jeffrey
- Bertacchi Valerio
- Besancon Marc
- Beschi Andrea
- Bhal Eshwen
- Bhandari Rohan
- Bhardwaj Ashutosh
- Bharti Monika
- Bhat Muzamil Ahmad
- Bhat Pushpalatha C.
- Bhatnagar Vipin
- Bhattacharya Rajarshi
- Bhattacharya Saptaparna
- Bhattacharya Satyaki
- Bhattacharya Soham
- Bheesette Srinidhi
- Bhowmik Debabrata
- Bhowmik Sandeep
- Bhyun Ji Hwan
- Bi Ran
- Bialkowska Helena
- Bianchini Lorenzo
- Bianco Michele
- Bianco Stefano
- Biasini Maurizio
- Biino Cristina
- Bilei Gian Mario
- Bilin Bugra
- Bilki Burak
- Bin Anuar Afiq Aizuddin
- Bisello Dario
- Black Kevin
- Blekman Freya
- Blinov Vladimir
- Bloch Daniel
- Bloch Philippe
- Bloom Kenneth
- Bluj Michal
- Blumenfeld Barry
- Boccali Tommaso
- Bocci Andrea
- Bodek Arie
- Boimska Bozena
- Boletti Alessio
- Bologna Simone
- Bols Emil Sørensen
- Bonacorsi Daniele
- Bonanomi Matteo
- Bonchev Miroslav
- Bonomally Shameena
- Boos Edouard
- Boran Fatma
- Borchsh Vladislav
- Borg Johan
- Borgonovi Lisa
- Bornheim Adolf
- Borras Kerstin
- Bortignon Pierluigi
- Bose Tulika
- Bossini Edoardo
- Botta Cristina
- Botta Valeria
- Boudoul Gaelle
- Bouhali Othmane
- Bourgatte Guillaume
- Bourilkov Dimitri
- Bozzo Marco
- Bragagnolo Alberto
- Braghieri Alessandro
- Braibant-Giacomelli Sylvie
- Brainerd Christopher
- Brandao Malbouisson Helena
- Brandt Stephanie
- Branson James G.
- Bravo Cameron
- Breedon Richard
- Breeze Shane
- Brew Christopher
- Brigliadori Luca
- Brigljevic Vuko
- Brinkerhoff Andrew
- Brivio Francesco
- Brochero Cifuentes Javier Andres
- Brom Jean-Marie
- Brondolin Erica
- Brooke James John
- Brown Robert M.
- Brunner David
- Bruno Giacomo
- Brzhechko Danyyl
- Brücken Erik
- Bucci Rachael
- Buccilli Andrew
- Buchanan James
- Buchmuller Oliver
- Bueghly James
- Bundock Aaron
- Bunin Pavel
- Bunkowski Karol
- Buontempo Salvatore
- Burkett Kevin
- Burkle Bjorn
- Burns Douglas
- Burt Kira
- Bury Florian Joel J.
- Busson Philippe
- Busza Wit
- Butalla Stephen
- Butler Joel Nathan
- Butler Philip H.
- Butz Erik
- Bylinkin Alexander
- Bylsma Ben
- Byszuk Adrian
- Cabrera Andrés
- Cabrillo Iban Jose
- Cadamuro Luca
- Caillol Cécile
- Cakir Altan
- Calandri Alessandro
- Calderon De La Barca Sanchez Manuel
- Calderon Alicia
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- Calligaris Luigi
- Calzaferri Simone
- Camen Camille
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- Campanini Renato
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- Camporesi Tiziano
- Candelise Vieri
- Canelli Maria Florencia
- Canepa Anadi
- Cankocak Kerem
- Capiluppi Paolo
- Cappati Alessandra
- Caputo Claudio
- Caraway Bryan
- Cardini Andrea
- Cardwell Bryan
- Carle Aurélien
- Carlin Roberto
- Carrera Jarrin Edgar
- Carrillo Montoya Camilo Andres
- Carrillo Moreno Salvador
- Cartiglia Nicolo
- Carvalho Antunes De Oliveira Alexandra
- Carvalho Wagner
- Casarsa Massimo
- Caspart René
- Cassese Antonio
- Castaldi Rino
- Castaneda Hernandez Alfredo
- Castilla-Valdez Heriberto
- Castro Andrea
- Cavallari Francesca
- Cavallo Francesca Romana
- Cavallo Nicola
- Cavanaugh Richard
- Ceard Ludivine
- Ceccarelli Rudy
- Cepaitis Vilius
- Cepeda Maria
- Cerati Giuseppe Benedetto
- Cerci Salim
- Cerminara Gianluca
- Cerrada Marcos
- Cerri Olmo
- Cetorelli Flavia
- Chabert Eric Christian
- Chahal Gurpreet Singh
- Chang Paoti
- Chang Philip
- Chanon Nicolas
- Chao Yuan
- Chapon Emilien
- Charaf Otman
- Charlot Claude
- Chatterjee Rajdeep Mohan
- Chatterjee Suman
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- Zacharopoulou Anna
- Zahid Sema
- Zaleski Shawn
- Zalewski Piotr
- Zanetti Marco
- Zarubin Anatoli
- Zarucki Mateusz
- Zecchinelli Angelo Giacomo
- Zenaiev Oleksandr
- Zenz Seth Conrad
- Zeuner Wolfram Dietrich
- Zghiche Amina
- Zhang Aobo
- Zhang Fengwangdong
- Zhang Huaqiao
- Zhang Jingyu
- Zhang Sijing
- Zhang Wenyu
- Zhang Yi
- Zhang Zhicai
- Zhao Jingzhou
- Zhizhin Ilia
- Zhokin Alexander
- Zhu De Hua
- Zhu Ren-Yuan
- Ziemons Tim Matthias
- Zientek Margaret
- Zlebcik Radek
- Zobec Joze
- Zoi Irene
- Zolkapli Zukhaimira
- Zorbakir Ibrahim Soner
- Zorbilmez Caglar
- Zotto Pierluigi
- Zou David
- Zucchetta Alberto
- Zumerle Gianni
- Zuo Xunwu
- Zuolo Davide
- Zygala Lara
- Álvarez Fernández Adrian
- Özçelik Özlem
- Publication venue
- 'American Physical Society (APS)'
- Publication date
- 01/01/2020
- Field of study
The first observation is reported of the combined production of three massive gauge bosons (VVV with V = W, Z) in proton-proton collisions at a center-of-mass energy of 13 TeV. The analysis is based on a data sample recorded by the CMS experiment at the CERN LHC corresponding to an integrated luminosity of 137 fb(-1). The searches for individualWWW, WWZ, WZZ, and ZZZ production are performed in final states with three, four, five, and six leptons (electrons or muons), or with two same-sign leptons plus one or two jets. The observed (expected) significance of the combinedVVV production signal is 5.7 (5.9) standard deviations and the corresponding measured cross section relative to the standard model prediction is 1.02(-0.23)(+0.26). The significances of the individual WWW and WWZ production are 3.3 and 3.4 standard deviations, respectively. Measured production cross sections for the individual triboson processes are also reported
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