73 research outputs found
Blindness Due to Polymicrogyria and Asymmetrical Dilation of the Lateral Ventricles in Standard Poodles
- Author
- Publication venue
- ScholarlyCommons
- Publication date
- 01/01/1994
- Field of study
Polymicrogyria and asymmetric dilation of the lateral ventricles were seen in related Standard poodles that had cortical blindness. Three of the affected dogs also had gait and postural abnormalities, and one of these had seizures.Two of the affected dogs were littermates. Thorough ophthalmologic and neurologic examinations (including electroretinography, electromyography, cerebrospinal fluid analysis, plain radiographs, and computerized tomography scans) revealed no significant abnormalities outside of the brain that would account for the blindness. Computerized tomography scans in three dogs demonstrated bilateral dilation of the lateral ventricles which was more severe in the right. All dogs were necropsied between 5 and 9 months of age and had strikingly similar brain abnormalities. Numerous small irregular gyri with shallow sulci covered the middle and caudal dorsal and lateral cerebral cortex. The bony ridges of the inner calvaria in this area conformed to the underlying microgyral pattern. The lateral ventricles were asymmetrically dilated with the right more severely affected, particularly in the occipital area, and the cortical grey and white matter, including the corpus callosum, were thinned in these areas. The third and fourth ventricles and mesencephalic aqueduct were normal. Histologically, there was thinning and simplification of the cortical grey matter with an increased density of medium to large neurons. The corona radiata and subcortical white matter were also thinner than normal with no evidence of demyelination of astrocytic scarring. This congenital anomaly of the visual cortex causing blindness in the Standard Poodle appears to be inherited as an autosomal recessive trait
Identification of the Rostral Migratory Stream in the Canine and Feline Brain
- Author
- A Bedard
- A Berman
- A Berman
- A Koestner
- Alison Isaacs
- Andreas Androutsellis-Theotokis
- AR Alexanian
- CH Vite
- Charles H. Vite
- D Lipsitz
- D Watson
- Deborah J. Watson
- DJ Waters
- DM Vail
- DR Kornack
- EA Milward
- F Doetsch
- F Luzzati
- FJ Muller
- G Stoica
- G Stoica
- H Klassen
- HL Rosomoff
- J Kimmelman
- JM Snyder
- JQ Trojanowski
- JR Menezes
- K Chandler
- K Lindblad-Toh
- K Sawamoto
- L Wang
- M Candolfi
- M Smitka
- MA Curtis
- Mark Haskins
- Melissa Lewis
- N Sanai
- N Sanai
- RJ Higgins
- RM Walton
- RM Walton
- S Couillard-Despres
- S Gil-Perotin
- S Rossignol
- SA Thomson
- Saafan Z. Malik
- T Jenkins
- TC Fitzgerald
- Thomas Van Winkle
- V Pencea
- X Tang
- Publication venue
- Public Library of Science
- Publication date
- 11/05/2012
- Field of study
In the adult rodent brain, neural progenitor cells migrate from the subventricular zone of the lateral ventricle towards the olfactory bulb in a track known as the rostral migratory stream (RMS). To facilitate the study of neural progenitor cells and stem cell therapy in large animal models of CNS disease, we now report the location and characteristics of the normal canine and feline RMS. The RMS was found in Nissl-stained sagittal sections of adult canine and feline brains as a prominent, dense, continuous cellular track beginning at the base of the anterior horn of the lateral ventricle, curving around the head of the caudate nucleus and continuing laterally and ventrally to the olfactory peduncle before entering the olfactory tract and bulb. To determine if cells in the RMS were proliferating, the thymidine analog 5-bromo-2-deoxyuridine (BrdU) was administered and detected by immunostaining. BrdU-immunoreactive cells were present throughout this track. The RMS was also immunoreactive for markers of proliferating cells, progenitor cells and immature neurons (Ki-67 and doublecortin), but not for NeuN, a marker of mature neurons. Luxol fast blue and CNPase staining indicated that myelin is closely apposed to the RMS along much of its length and may provide guidance cues for the migrating cells. Identification and characterization of the RMS in canine and feline brain will facilitate studies of neural progenitor cell biology and migration in large animal models of neurologic disease
Targeting of mutant hogg1 in mammalian mitochondria and nucleus: effect on cellular survival upon oxidative stress
- Author
- A Viswanathan
- Aditi Chatterjee
- AP Grollman
- AW Dobson
- BN Ames
- CM Hughes
- D Thomas
- David Sidransky
- DC Malins
- DC Thomas
- DC Wallace
- DC Wallace
- DE Sawyer
- DL Croteau
- E Mambo
- E Mambo
- Elizabeth Mambo
- ET Donnelly
- F Le Page
- FM Yakes
- H Aburatani
- H Tokiwa
- HM Nash
- I Kuraoka
- J Cadet
- JH Santos
- JP Radicella
- JW Hyun
- K Arai
- K Nishioka
- K Sakumi
- KC Cheng
- KK Singh
- L Haracska
- LI Rachek
- M Audebert
- M Audebert
- M Dizdaroglu
- M Moriya
- M Moriya
- M Orth
- M Osterod
- M Takao
- MC Alley
- MF Beal
- ML Michaels
- ML Wood
- MS Fliss
- P Fortini
- P Jaruga
- PA van der Kemp
- R Lu
- R Shimoda
- RN Lightowlers
- S Ayala-Torres
- S Boiteux
- S Chevillard
- S DiMauro
- S Nowak
- SA Winkle
- T Peng
- TA Rosenquist
- Theodore DeWeese
- TT Ni
- Y Gu
- Yonggang Zhang
- Publication venue
- BioMed Central
- Publication date
- 01/01/2006
- Field of study
BACKGROUND: Oxidative damage to mitochondrial DNA has been implicated as a causative factor in a wide variety of degenerative diseases, aging and cancer. The modified guanine, 7,8-dihydro-8-oxoguanine (also known as 8-hydroxyguanine) is one of the major oxidized bases generated in DNA by reactive oxygen species and has gained most of the attention in recent years as a marker of oxidative DNA injury and its suspected role in the initiation of carcinogenesis. 8-hydroxyguanine is removed by hOgg1, a DNA glycosylase/AP lyase involved in the base excision repair pathway. METHODS: We over-expressed wild type and R229Q mutant hOGG1 in the nucleus and mitochondria of cells lacking mitochondrial hOGG1 expression through an expression vector containing nuclear and mitochondrial targeting sequence respectively. We used quantitative real time PCR to analyze mtDNA integrity after exposure to oxidative damaging agents, in cells transfected with or without mitochondrially-targeted mutant hogg1. RESULT: Over-expression of wild type hOgg1 in both nucleus and mitochondria resulted in increased cellular survival when compared to vector or mutant over-expression of hOGG1. Interestingly, mitochondrially-targeted mutant hogg1 resulted in more cell death than nuclear targeted mutant hogg1 upon exposure of cells to oxidative damage. Additional we examined mitochondrial DNA integrity after oxidative damage exposure using real-time quantitative PCR. The presence of mutant hogg1 in the mitochondria resulted in reduced mitochondrial DNA integrity when compared to the wild type. Our work indicates that the R229Q hOGG1 mutation failed to protect cells from oxidative damage and that such mutations in cancer may be more detrimental to cellular survival when present in the mitochondria than in the nucleus. CONCLUSION: These findings suggest that deficiencies in hOGG1, especially in the mitochondria may lead to reduced mitochondrial DNA integrity, consequently resulting in decreased cell viability
A Scalable System for Production of Functional Pancreatic Progenitors from Human Embryonic Stem Cells
- Author
- A Maitra
- A Rezania
- Alan D. Agulnick
- Alistair Z. Wilson
- Allan J. Robins
- AM Shapiro
- AM Shapiro
- Amanda B. McLean
- Anindita Bhoumik
- Anne G. Bang
- AP Van Winkle
- B Blum
- BW Phillips
- C Verdier
- Carl Haakmeester
- Chad E. Green
- DE Kehoe
- DL Eizirik
- E Kroon
- Emmanuel E. Baetge
- Eric S. Sherrer
- Eugene P. Brandon
- Evert J. Kroon
- Francis C. Lynn
- FW Quimby
- GK Geiss
- GO Clark
- H Okamoto
- H Singh
- Holly Y. Young
- HY Young
- I Barbaric
- Igor Cepa
- J Cai
- J Dominguez-Bendala
- Janice K. Payne
- JH Shim
- JK Mfopou
- JM Crook
- Jonathan R. Kelly
- JS Draper
- Justin Kerr
- K Ley
- KA D’Amour
- KA D’Amour
- Kelly G. Ross
- Kevin A. D’Amour
- Kuniko Kadoya
- L Li
- L Wang
- Laura A. Martinson
- LT Lock
- M Amit
- M Hosokawa
- M Johannesson
- M. Josephine Babin
- Mark A. Moorman
- MC Nostro
- MD McCall
- MD Ungrin
- Mike Richardson
- OG Kelly
- Olivia G. Kelly
- P Fortina
- R Olmer
- Rosemary M. Cesario
- S Matsumoto
- SG Straub
- SK Oh
- SN Brimble
- TC Schulz
- Thomas C. Schulz
- V Olariu
- W Jiang
- X Chen
- Xuehong Song
- Publication venue
- Public Library of Science
- Publication date
- 01/01/2012
- Field of study
Development of a human embryonic stem cell (hESC)-based therapy for type 1 diabetes will require the translation of proof-of-principle concepts into a scalable, controlled, and regulated cell manufacturing process. We have previously demonstrated that hESC can be directed to differentiate into pancreatic progenitors that mature into functional glucose-responsive, insulin-secreting cells in vivo. In this study we describe hESC expansion and banking methods and a suspension-based differentiation system, which together underpin an integrated scalable manufacturing process for producing pancreatic progenitors. This system has been optimized for the CyT49 cell line. Accordingly, qualified large-scale single-cell master and working cGMP cell banks of CyT49 have been generated to provide a virtually unlimited starting resource for manufacturing. Upon thaw from these banks, we expanded CyT49 for two weeks in an adherent culture format that achieves 50–100 fold expansion per week. Undifferentiated CyT49 were then aggregated into clusters in dynamic rotational suspension culture, followed by differentiation en masse for two weeks with a four-stage protocol. Numerous scaled differentiation runs generated reproducible and defined population compositions highly enriched for pancreatic cell lineages, as shown by examining mRNA expression at each stage of differentiation and flow cytometry of the final population. Islet-like tissue containing glucose-responsive, insulin-secreting cells was generated upon implantation into mice. By four- to five-months post-engraftment, mature neo-pancreatic tissue was sufficient to protect against streptozotocin (STZ)-induced hyperglycemia. In summary, we have developed a tractable manufacturing process for the generation of functional pancreatic progenitors from hESC on a scale amenable to clinical entry
Genome-wide association identifies nine common variants associated with fasting proinsulin levels and provides new insights into the pathophysiology of type 2 diabetes.
- Author
- Abecasis Goncalo
- Abecasis Gonçalo R.
- Aben Katja K.
- Absher Devin
- Aherrahrou Zouhair
- Ahlqvist Emma
- Ahmadi Kourosh
- Ahmed Nabeel
- Alavere Helene
- Alibrandi Maria T S
- Allayee Hooman
- Almgren Peter
- Altshuler David
- Amin Najaf
- Anand Sonia S.
- Andersen Karl
- Anderson Jeffrey L.
- Ardissino Diego
- Ardlie Kristin
- Armitage Jane
- Arnold Alice M.
- Aspelund Thor
- Assimes Themistocles L.
- Assmann Gerd
- Atwood Larry D.
- Aulchenko Yurii S.
- Azhar Muhammad
- Balkau Beverley
- Ball Stephen G.
- Balmforth Anthony J.
- Barbalic Maja
- Barker Adam
- Barker David J P
- Barlassina Christina
- Barlera Simona
- Barnes Daniel
- Barnes Timothy A.
- Barrett Amy
- Barroso H
- Barroso Inês
- Bataille Veronique
- Becker Diane M.
- Becker Lewis C.
- Beckmann Jacques S.
- Beilby John P.
- Ben-Shlomo Yoav
- Benediktsson Rafn
- Bennett Amanda J.
- Berger Klaus
- Bergman Richard N.
- Bergmann Sven
- Bernd Sonja I.
- Berndt Sonja I
- Biebermann Heike
- Bis Joshua C.
- Blagieva Roza
- Blakemore Alexandra I F
- Blankenberg Stefan
- Boehm Bernhard O.
- Boehnke Michael
- Boehnke Mike
- Boeing Heiner
- Boekholdt S. Matthijs
- Boerwinkle Eric
- Boes Tanja
- Bonnycastle Lori L.
- Boomsma Dorret I.
- Borecki Ingrid B.
- Bornstein Stefan R.
- Boström Kristina Bengtsson
- Bouatia-Naji Nabila
- Bowman Louise
- Bragi Walters G.
- Braund Peter S.
- Bravenboer Bert
- Brown Morris J.
- Buchanan Thomas A.
- Bumpstead Suzannah
- Burnett Mary Susan
- Burtt Noisël P.
- Busonero Fabio
- Buysschaert Ian
- Cambien Francois
- Campbell Harry
- Cappuccio Francesco P.
- Cardiogenics [Unknown]
- Carlquist John F.
- Cauchi Stephane
- Caulfield Mark
- Cavalcanti-Proença Christine
- Chambers John C.
- Chanock Stephen J.
- Charpentier Guillaume
- Chasman Daniel I.
- Chatterjee Nilanjan
- Chen Chih Mei
- Chen Han
- Chen Li
- Chines Peter S.
- Cichon Sven
- Clarke Robert
- Codd Veryan
- Coin Lachlan
- Collins Francis S.
- Collins Rory
- Connell John
- Cooper Cyrus C.
- Cooper Matthew N.
- Cornelis Marilyn
- Couper David J.
- Crawford Gabe
- Cupples L. Adrienne
- Daly Mark J.
- Danesh John
- Davies Robert W.
- Day Ian N M
- de Faire Ulf
- Dedoussis George
- Dehghan Abbas
- Deloukas Panos
- Demissie Serkalem
- den Heijer Martin
- Dennison Elaine M.
- Dermitzakis Emmanouil T.
- Devaney Joseph M.
- di Meglio Paola
- Diemert Patrick
- Dimas Antigone S.
- Dina Christian
- Dixon Anna L.
- Do Ron
- Doering Angela
- Doney Alex S F
- Donnelly Peter
- Dorret I Boomsma
- Duan Jubao
- Dupuis Josée
- Durbin Richard
- Ebrahim Shah
- Eifert Sandra
- Eiriksdottir Gudny
- El Mokhtari Nour Eddine
- Elliott Amanda L.
- Elliott Katherine S.
- Elliott Paul
- Ellis Stephen G.
- Elosua Roberto
- Engert James C.
- Epstein Stephen E.
- Erdmann Jeanette
- Erdos Michael R.
- Eric E Schadt
- Eriksson Johan G.
- Eriksson Per
- Esko Tõnu
- Estrad Karol
- Estrada Karol
- Eury Elodie
- Facheris Maurizio F.
- Farooqi I. Sadaf
- Farrall Martin
- Feitosa Mary F.
- Felix Stephan B.
- Ferrannini Ele
- Ferreir Teresa
- Ferreira Teresa
- Fischer Marcus
- Fischer-Posovszky Pamela
- Fisher Eva
- Florez Jose C.
- Folkersen Lasse
- Folsom Aaron R.
- Forsen Tom J.
- Fox Caroline S.
- Franklin Christopher S.
- Franzosi Maria Grazia
- Frayling Timothy M.
- Freimer Nelson B.
- Freyer Jennifer
- Friedrich Nele
- Froguel Philippe
- Frossard Philippe
- Fu Mao
- Gaget Stefan
- Ganser Martha
- Gardezi Ali
- Gejman Pablo V.
- Geus Eco J C
- Gieger Christian
- Gigante Bruna
- Girelli Domenico
- Gjesing Anette P.
- Glass Daniel
- Glazer Nicole L.
- Gloyn Anna L.
- Goddard Michael E.
- Goel Anuj
- Goodall Alison H.
- Goyette Philippe
- Grallert Harald
- Grarup Niels
- Green Fiona
- Green Todd
- Greenawalt Danielle M.
- Gretarsdottir Solveig
- Griffin Simon
- Groop Leif
- Groop Leif C.
- Groves Christopher J.
- Grundberg Elin
- Gräßler Jürgen
- Grönberg Henrik
- Gu Harvest
- Gudnason Vilmundur
- Guiducci Candace
- Gulcher Jeffrey R.
- Gustafsso Stefan
- Gustafsson Stefan
- Gyllensten Ulf
- Hadjadj Samy
- Hall Alistair S.
- Hall Per
- Halperin Eran
- Hammond Christopher J.
- Hammond Naomi
- Hamsten Anders
- Han Chen
- Hansen Torben
- Haritunians Talin
- Harris Tamara B.
- Hartikainen Anna Liisa
- Hassanali Neelam
- Hattersley Andrew T.
- Havulinna Aki S.
- Hayes Richard B.
- Hayward Caroline
- Hazen Stanley L.
- Heard-Costa Nancy L.
- Heath Andrew C.
- Hebebrand Johannes
- Hedman Åsa K.
- Hei Iris M.
- Heid Iris M
- Heinrich Joachim
- Hellénius Mai Lis
- Hengstenberg Christian
- Herder Christian
- Hicks Andrew A.
- Hide Winston A.
- Hinney Anke
- Hirschhorn Joel N.
- Hitman Graham A.
- Hoesel Volker
- Hofman Albert
- Hofmann Oliver M.
- Holm Hilma
- Homuth Georg
- Hopewell Jemma C.
- Horikoshi Momoko
- Horne Benjamin D.
- Hottenga Jouke Jan
- Hu Frank B.
- Hui Jennie
- Huikuri Heikki V.
- Hunter David J.
- Huth Cornelia
- Hveem Kristian
- Ida Chen Yii Der
- Igl Wilmar
- Illig Thomas
- Ingelsson Erik
- Ingle Catherine
- Iribarren Carlos
- Ishaq Muhammad
- Isomaa Bo
- Jackso Anne U.
- Jackson Anne U.
- Jacobs Kevin B.
- James Alan L.
- Jameson Karen A.
- Jansson John Olov
- Jarick Ivonne
- Jarvelin Marjo Riitta
- Jewell Elizabeth
- Johansson Åsa
- John Ulrich
- Johnson Paul
- Johnson Paul R V
- Johnson Toby
- Jones Gregory T.
- Jousilahti Pekka
- Jukema J. Wouter
- Jula Antti
- Jørgensen Torben
- Kaakinen Marika
- Kaiser Michael A.
- Kajantie Eero
- Kanoni Stavroula
- Kao Wen H L
- Kaplan Lee M.
- Kaplan Robert C.
- Kaprio Jaakko
- Karpe Fredrik
- Kastelein John J P
- Kathiresan Sekar
- Kerr-Conte Julie
- Ketkar Shamika
- Kettunen Johannes
- Khaw Kay Tee
- Kiemeney Lambertus A.
- Kilpeläine Tuomas O.
- Kilpeläinen Tuomas O
- Kinnunen Leena
- Klopp Norman
- Knowles Joshua W.
- Kolcic Ivana
- Kolovou Genovefa
- Kong Augustine
- Kooner Angad S.
- Kooner Jaspal S.
- Koskinen Seppo
- Kovacs Peter
- Kraft Peter
- Krude Heiko
- Kutalik Zoltán
- Kuulasmaa Teemu
- Kuusisto Johanna
- Kvaløy Kirsti
- Kyriakou Theodosios
- Kähönen Mika
- König Inke R.
- Laakso Markku
- Laaksonen Reijo
- Laitinen Jaana
- Lambrechts Diether
- Lamina Claudia
- Langenberg Claudia
- Lango Allen Hana
- Lantieri Olivier
- Lanzani Chiara
- Launer Lenore J.
- Lauritzen Torsten
- Lawlor Debbie A.
- Lawrence Robert W.
- Leander Karin
- Lecoeur Cecile
- Lehtimäki Terho
- Lettre Guillaume
- Levinson Douglas F.
- Li Man
- Li Mingyao
- Li Shengxu
- Lian Liming
- Liang Liming
- Lieb Wolfgang
- Lieverse Aloysius
- Lind Lars
- Lindgre Cecilia M.
- Lindgren Cecilia M.
- Linksted Pamela
- Liu Jianjun
- Lokki Marja Liisa
- Loley Christina
- Loos Ruth J F
- Lorentzon Mattias
- Lotery Andrew J.
- Lua Jian'an
- Luan Jian'an
- Luben Robert N.
- Ludwig Barbara
- Lyssenko Valeriya
- Macciardi Fabio
- MAGIC [Unknown]
- Makrilakis Konstantinos
- Mallick Nadeem
- Mangino Massimo
- Mannila Maria Nastase
- Manning Alisa K.
- Mannucci Pier M.
- Manunta Paolo
- Maouche Seraya
- Marek Diana
- Marre Michel
- Martin Nicholas G.
- Martinelli Nicola
- Martínez-Larrad María Teresa
- McArdle Wendy L.
- McCarroll Steve A.
- McCarroll Steven A.
- McCarthy Anne
- McCarthy Mark
- McCulloch Laura J.
- McKeown Pascal P.
- McKnight Barbara
- McPherson Ruth
- Meigs James B.
- Meisinger Christa
- Meitinger Thomas
- Melander Olle
- Memon Fazal ur Rehman
- Merlini Pier Angelica
- Metspalu Andres
- Meyre David
- Midthjell Kristian
- Min Josine L.
- Moffatt Miriam F.
- Mohlke Karen L.
- Mond Keri L.
- Monda Keri L
- Montgomery Grant W.
- Montgomery Stephen B.
- Mooser Vincent
- Morgan Thomas
- Morken Mario A.
- Morris Andrew D.
- Morris Andrew P.
- Muhlestein Joseph B.
- Mulic Rosanda
- Munroe Patricia B.
- Musunuru Kiran
- Myers Richard H.
- Mäg Reedik
- Mägi Reedik
- Mälarstig Anders
- März Winfried
- Mühleisen Thomas W.
- Münzel Thomas
- Nahrstaedt Janja
- Narisu Narisu
- Navarro Pau
- Nelis Mari
- Nelson Christopher P.
- Nemes James
- Nemesh James
- Nestle Frank O.
- Neville Matt J.
- Ngwa Julius S.
- Nica Alexandra C.
- Nieminen Markku S.
- Nilesh J Samani
- Nilsson Peter
- Nisbet James
- North Kari E.
- Nyholt Dale R.
- Nöthen Markus M.
- O'Connell Jeffrey R.
- O'Donnel Christopher J.
- O'Donnell Christopher J.
- O'Rahilly Stephen
- O'Rahilly Steve
- Offer Alison
- Ohlsson Claes
- Ohrvik John
- Olivieri Oliviero
- Olsson Gunnar
- Ong Ken K.
- Ongen Halit
- Oostra Ben
- Osmond Clive
- Ostenson Claes-Göran
- Ouwehand Willem H.
- Owen Katharine R.
- Palmer Colin N A
- Palmer Lyle J.
- Pankow James S.
- Par Ju Hyun
- Parish Sarah
- Park Ju-Hyun
- Parker Alex N.
- Parts Leopold
- Paré Guillaume
- Pascoe Laura
- Patel Riyaz S.
- Patterson Chris C.
- Pattou François
- Payne Felicity
- Peden John F.
- Pedersen Oluf
- Pellikka Niina
- Peltonen Leena
- Penninx Brenda W.
- Perola Markus
- Perry John R B
- Peter M Visscher
- Peters Annette
- Peters Marjolein J.
- Petersen Ann Kristin
- Peto Richard
- Petrie John R.
- Peyvandi Flora
- Pichler Irene
- Pietiläinen Kirsi H.
- Platou Carl
- Platou Carl G P
- Polasek Ozren
- Potter Simon
- Pouta Anneli
- Pramstaller Peter P.
- Preuss Michael
- Proença Christine
- Prokopenko Inga
- Purcell Shaun
- Qi Lu
- Qu Liming
- Quertermous Thomas
- Quyyumi Arshed A.
- Rader Daniel J.
- Rafelt Suzanne
- Raitakari Olli
- Rallidis Loukianos S.
- Randal Joshua C.
- Randall Joshua C
- Rasheed Asif
- Rathmann Wolfgang
- Raychaudhuri Soumya
- Rayner N. William
- Rayner Nigel W.
- Reilly Muredach P.
- Reinehr Thomas
- Rice Catherine
- Ridderstråel Martin
- Ridderstråle Martin
- Ridker Paul M.
- Rief Winfried
- Ripatti Samuli
- Rissanen Aila
- Rivadeneira Fernando
- Roberts Robert
- Robertson Neil R.
- Rocheleau Ghislain
- Roden Michael
- Rosendaal Frits R.
- Rubin Diana
- Rudan Igor
- Ruokonen Aimo
- Rust Stephan
- Rybin Denis
- Rzehak Peter
- Ríos Manuel Serrano
- Sabater-Lleal Maria
- Saleheen Danish
- Salomaa Veikko
- Samad Adbus
- Samani Nilesh
- Sampietro M. Lourdes
- Sampson Michael J.
- Samuel Maria
- Sanders Alan R.
- Sandholt Camilla
- Sandhu Manj S.
- Sandhu Manjinder S.
- Sanna Serena
- Saramies Jouko
- Savolainen Markku J.
- Saxena Richa
- Sayer Avan A.
- Schadt Eric
- Scherag Andre
- Scherag Susann
- Schillert Arne
- Schipf Sabine
- Schlessinger David
- Schreiber Stefan
- Schrezenmeir Jürgen
- Schunkert Heribert
- Schwartz Stephen M.
- Schwarz Peter E H
- Schäfer Arne
- Scott James
- Scott Laura J.
- Seedorf Udo
- Segrè Ayellet V.
- Sehmi Joban
- Sekowska Magdalena
- Sennblad Bengt
- Shah Nabi
- Shaun Purcell
- Shi Jianxin
- Shields Beverley M.
- Shrader Peter
- Shuldiner Alan R.
- Sigurdsson Gunnar
- Sijbrands Eric
- Silander Kaisa
- Silveira Angela
- Sinisalo Juha
- Siscovick David S.
- Sivananthan Mohan
- Sivapalaratnam Suthesh
- Sladek Rob
- Sleight Peter
- Small Kerrin
- Smit Jan H.
- Smith Albert
- Smith George Davey
- Smith Tamara B.
- Snoep Jaapjan D.
- Soranzo Nicole
- Sovio Ulla
- Sparsø Thomas
- Spector Timothy D.
- Speliote Elizabeth K.
- Speliotes Elizabeth K
- Spertus John A.
- Stancakova Alena
- Stark Klaus
- Stefansson Kari
- Stein Lincoln D.
- Steinthorsdotti Valgerdur
- Steinthorsdottir Valgerdur
- Stephens Jonathan
- Stewart Alexandre F R
- Stirrups Kathy
- Stoll Monika
- Strachan David P.
- Strassburger Klaus
- Strawbridge Rona
- Stringha Heather M.
- Stringham Heather M.
- Stumvoll Michael
- Sun Qi
- Surakka Ida
- Surdulescu Gabriela
- Swift Amy J.
- Syvänen Ann Christine
- Tammesoo Mari Liis
- Taneera Jalal
- Tang W. H Wilson
- Tardif Jean Claude
- Teder-Laving Maris
- Tennstedt Stephanie
- Terho Lehtimäki
- Teslovich Tanya M.
- Thiering Elisabeth
- Thompson John R.
- Thomson Brian
- Thorand Barbara
- Thorgeirsson Gudmundur
- Thorleifsso Gudmar
- Thorleifsson Gudmar
- Thorsteinsdottir Unnur
- Tichet Jean
- Timpson Nicholas J.
- Tognoni Gianni
- Tomaszewski Maciej
- Travers Mary
- Tuomi Tiinamaija
- Tuomilehto Jaakko
- Turrini Fabiola
- Tyrer Jonathan P.
- Tzenova Bell Jordana
- Tönjes Anke
- Uda Manuela
- Uitterlinden Andre
- Uitterlinden Andre G.
- Uitterlinden André
- Valle Timo T.
- van Dam Rob M.
- van Duijn Cornelia M.
- van Haeften Timon W.
- van Herpt Thijs
- van Hoek Mandy
- van Meurs Joyce B.
- van Ommen Gert Jan
- van Rij Andre M.
- van Vliet Jana V
- van Vliet-Ostaptchouk Jana V.
- van Wingerden Sophie
- van't Hooft Ferdinand
- Vatin Vincent
- Vedanta Sailaja
- Vedantam Sailaja
- Viikari Jorma
- Visscher Peter M.
- Visvikis-Siest Sophie
- Vitart Veronique
- Vogel Carla I G
- Voight Benjamin F.
- Wabitsch Martin
- Waeber Gérard
- Waite Lindsay L.
- Walker Mark
- Wallaschofski Henri
- Walter G. Bragi
- Wareham Nicholas J.
- Wareham Nick J.
- Watanabe Richard M.
- Watkins Hugh
- Weedo Michael N.
- Weedon Michael N.
- Welch Ryan
- Wells George A.
- Weyan Robert J.
- Weyant Robert J
- Wheele Eleanor
- Wheeler Eleanor
- White Charles C.
- Wichmann H. Erich
- Widen Elisabeth
- Wiegand Susanna
- Wijmenga Cisca
- Wiklund Fredrik
- Wild Philipp S.
- Wild Sarah H.
- Wilk Alicja
- Wille Cristen J.
- Willemsen Gonneke
- Willenborg Christina
- Willer Cristen J.
- Wilson James F.
- Winkle Thomas W.
- Winkler Thomas W
- Witte Daniel R.
- Witteman Jacqueline
- Witteman Jacqueline C.
- Witteman Jaqueline C M
- Woo Andrew R.
- Wood Andrew R
- Workalemah Tsegaselassie
- Workalemahu Tsegaselassie
- Wright Alan F.
- Wright Benjamin J.
- Wu Guanming
- Xie Weijia
- Xu Jianfeng
- Yang Jian
- Yang Tsun Po
- Ye Shu
- Zabena Carina
- Zaidi Moazzam
- Zaman Khan Shah
- Zeggini Eleftheria
- Zeller Tanja
- Zethelius Björn
- Zgaga Lina
- Zhang Qunyuan
- Zhang Weihua
- Zhao Jing Hua
- Ziegler Andreas
- Zillikens M. Carola
- Zitting Paavo
- Zondervan Krina T.
- Öhrvik John
- Östenson Claes Göran
- Publication venue
- Diabetes
- Publication date
- 01/01/2011
- Field of study
OBJECTIVE: Proinsulin is a precursor of mature insulin and C-peptide. Higher circulating proinsulin levels are associated with impaired β-cell function, raised glucose levels, insulin resistance, and type 2 diabetes (T2D). Studies of the insulin processing pathway could provide new insights about T2D pathophysiology. RESEARCH DESIGN AND METHODS: We have conducted a meta-analysis of genome-wide association tests of ∼2.5 million genotyped or imputed single nucleotide polymorphisms (SNPs) and fasting proinsulin levels in 10,701 nondiabetic adults of European ancestry, with follow-up of 23 loci in up to 16,378 individuals, using additive genetic models adjusted for age, sex, fasting insulin, and study-specific covariates. RESULTS: Nine SNPs at eight loci were associated with proinsulin levels (P < 5 × 10(-8)). Two loci (LARP6 and SGSM2) have not been previously related to metabolic traits, one (MADD) has been associated with fasting glucose, one (PCSK1) has been implicated in obesity, and four (TCF7L2, SLC30A8, VPS13C/C2CD4A/B, and ARAP1, formerly CENTD2) increase T2D risk. The proinsulin-raising allele of ARAP1 was associated with a lower fasting glucose (P = 1.7 × 10(-4)), improved β-cell function (P = 1.1 × 10(-5)), and lower risk of T2D (odds ratio 0.88; P = 7.8 × 10(-6)). Notably, PCSK1 encodes the protein prohormone convertase 1/3, the first enzyme in the insulin processing pathway. A genotype score composed of the nine proinsulin-raising alleles was not associated with coronary disease in two large case-control datasets. CONCLUSIONS: We have identified nine genetic variants associated with fasting proinsulin. Our findings illuminate the biology underlying glucose homeostasis and T2D development in humans and argue against a direct role of proinsulin in coronary artery disease pathogenesis
The Physics of the B Factories
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- A Abashian
- A. A. Botov
- A. A. Grillo
- A. A. Korol
- A. A. Salnikov
- A. Abashian
- A. Adametz
- A. Agarwal
- A. Anjomshoaa
- A. B. Breon
- A. Bala
- A. Bay
- A. Bondar
- A. Bozek
- A. Buzzo
- A. C. Forti
- A. C. Wren
- A. Calcaterra
- A. Cecchi
- A. Cervelli
- A. Ceseracciu
- A. Chen
- A. Chuvikov
- A. Cotta Ramusino
- A. Crescente
- A. Cunha
- A. D. Bukin
- A. Das
- A. de Lesquen
- A. De Silva
- A. Dorigo
- A. Drutskoy
- A. Dvoretskii
- A. D’Orazio
- A. E. Rubin
- A. Farbin
- A. Fella
- A. Filippi
- A. Frey
- A. G. Denig
- A. Gaidot
- A. Garmash
- A. Gaz
- A. Go
- A. Gordon
- A. Gorišek
- A. Hafner
- A. Hanushevsky
- A. Hasan
- A. Hauke
- A. Hicheur
- A. Höcker
- A. I. Panova
- A. I. Robertson
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- A. Kirk
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- A. Kreisel
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- A. Perazzo
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- A. Petrella
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- A. Satpathy
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- A. Soffer
- A. Soha
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- A.S. Fisher
- Aleksan
- ALEPH CDF, D0, DELPHI, L3, OPAL, SLD and the LEP, Tevatron and SLD Electroweak and Heavy Flavour Working Groups
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- Czyz Rodrigo
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- D. Altenburg
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- D. Bernard
- D. Bettoni
- D. Boutigny
- D. Breton
- D. C. Williams
- D. Cinabro
- D. Cote
- D. del Re
- D. Derkach
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- D. E. Azzopardi
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- D. M. Asner
- D. M. Rodriguez
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- D. Marlow
- D. Matvienko
- D. Mohapatra
- D. Monorchio
- D. N. Brown
- D. Nelson
- D. Newman-Coburn
- D. P. Coupal
- D. P. Stoker
- D. Piccolo
- D. R. Johnson
- D. R. Lavin
- D. R. Muller
- D. R. Peimer
- D. S. Bailey
- D. S. Best
- D. S. Chao
- D. S. Smith
- D. S. Yan
- D. Santel
- D. Semmler
- D. Smith
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- D. Su
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- D. van Winkle
- D. W. G. S. Leith
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- D. Wallom
- D. Z. Shen
- D. Zander
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- D. Žontar
- Datta Browder
- De Rujula
- Degrassi Ciuchini
- Degrassi Ciuchini
- Dokshitzer Azimov
- Dunietz Aleksan
- DW Sivers
- D’Alesio Bacchetta
- E. A. Antillon
- E. A. Eckhart
- E. A. Kravchenko
- E. Antonioli
- E. Banas
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- E. C. Martin
- E. Campagna
- E. Charles
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- E. Di Marco
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- E. Soderstrom
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- Ewerth Bobeth
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- F. Di Lodovico
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- F. Evangelisti
- F. F. Wilson
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- F. Fang
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- F. Forti
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- F. G. O’Neill
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- F. Le Diberder
- F. Liu
- F. Mandl
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- F. Ohno
- F. Palombo
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- F. R. Wappler
- F. Raffaelli
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- F. Safai Tehrani
- F. Salvatore
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- Golowich Burdman
- Golowich Donoghue
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- Grojean Csaki
- Gronau Beneke
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- Grossman Giri
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- Y. W. Chang
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- Y. Y. Gao
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- Y. Yoshimura
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- Yu.I. Skovpen
- Z. C. Clifton
- Z. Doležal
- Z. Drásal
- Z. G. Zhao
- Z. Georgette
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- Z. J. Guo
- Z. M. Zhu
- Z. Natkaniec
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- Z. P. Zhang
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- Z. W. Yin
- Z. Yasin
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- Z. Z. Xu
- Publication venue
- 'Springer Science and Business Media LLC'
- Publication date
- 01/01/2014
- Field of study
This work is on the Physics of the B Factories. Part A of this book contains a brief description of the SLAC and KEK B Factories as well as their detectors, BaBar and Belle, and data taking related issues. Part B discusses tools and methods used by the experiments in order to obtain results. The results themselves can be found in Part C
withdrawn 2017 hrs ehra ecas aphrs solaece expert consensus statement on catheter and surgical ablation of atrial fibrillation
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- Young-Hoon Kim
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- Zuern
- Publication venue
- Publication date
- 01/01/2017
- Field of study
n/
Interventions to cultivate physician empathy: a systematic review
- Author
- A Chunharas
- A Liénard
- A Liénard
- AD Misra-Hebert
- AD Poole
- AM Bays
- AR Bond
- AW Dow
- BN Sripada
- BT Lim
- BW Newton
- C Fernández-Olano
- C Ghetti
- Chris Feudtner
- CN Hart
- CT Ozcan
- D Farnill
- D Garcia
- D Kramer
- D Rakel
- D Razavi
- DC Chen
- DC Chen
- DL Roter
- DL Roter
- DP Rakel
- DS Morse
- DW Easter
- F Derksen
- FM Wolf
- G Airagnes
- H Eide
- H Harlak
- H Riess
- H Riess
- HB Bayne
- HB Beckman
- HM Bosse
- HR Winefield
- HS Attar
- J Shapiro
- J Shapiro
- J Tiuraniemi
- JA Tulsky
- James Womer
- JB Daeppen
- Jennifer K Walter
- JM Hemmerdinger
- JM Satterfield
- JO Schell
- JT Pacala
- K Berg
- KA Bonvicini
- KA Stepien
- KB Zolnierek
- KD Bertakis
- KI Pollack
- KI Pollak
- KM Glasner
- KP Cataldo
- KT Yang
- L Fallowfield
- LF DiLalla
- LJ Van Winkle
- LM Bellini
- M Hojat
- M Hojat
- M Hojat
- M Hojat
- M Hojat
- M Hojat
- M Hojat
- M Hojat
- M Neumann
- M Schweller
- MA Cahan
- MA Stewart
- MF Dikici
- MM Lobchuk
- MR Thomas
- MS Krasner
- N Delvaux
- N Karaoglu
- O Cinar
- P Varkey
- P Walters
- PJ Moore
- R Pedersen
- R Smith
- R Zachariae
- RF Kushner
- RM Epstein
- RM Epstein
- RW Sanson-Fisher
- RW Sanson-Fisher
- RW Squier
- S Lelorain
- S Mitchell
- S Rosenthal
- S Tavakol
- SA Sands
- SJ Scholer
- SL Shapiro
- SM Shapiro
- SS Kim
- SW Mercer
- T Norfolk
- TD Shanafelt
- V Jenkins
- VK Fine
- W Bunn
- W Levinson
- W Levinson
- Z Goore
- Zak Kelm
- Publication venue
- 'Springer Science and Business Media LLC'
- Publication date
- Field of study
The Physics of the B Factories
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- Abashian A.
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- Publication venue
- Springer Verlag
- Publication date
- 29/01/2015
- Field of study
Adding 6 months of androgen deprivation therapy to postoperative radiotherapy for prostate cancer: a comparison of short-course versus no androgen deprivation therapy in the RADICALS-HD randomised controlled trial
- Author
- Abab Julie
- Abbas Ali
- Abbassi Sara
- Abd Alazeez Mohamed
- Abdulwahid Danya
- Abdulwahid Danya
- Abed Jessy
- Adab Fawzi
- Adams Marion
- Adamson Vanessa
- Addison Anglise
- Adeyoju Adebanji
- Adinkra Victoria
- Adnaan Jamila
- Afzal Naveed
- Agdiran Didem
- Aggarwal Ajay
- Ahamadali Sheefa
- Ahmad Belal
- Ahmed Ilyas
- Ahmed Imtiaz
- Ahmed Shahida
- Aiku Abimbola
- Ainsworth Sarah
- Ainsworth Sarah
- Aitken Katherine
- Ajzensztejn Daniel
- Akhtar Naeem
- Al-Chamali Hiba
- Al-hasso Abdulla
- Al-hasso Abdulla
- Al-Samarraie Amir
- Albrecht Virginia
- Alcock Christopher
- Alder Leanne
- Alderton Kate
- Aldous Mary
- Ali Jennyfa
- Ali Maryam
- Ali Zulfiqer
- Ali Zulfiqer
- Allan Elaine
- Allan Elaine
- Allen Julie
- Allen Kirsten
- Allen Rachael
- Allen Susan
- Allison Joanna
- Allison Michele
- Alonzi Roberto
- AlRashdan Abdulla
- Alzouebi Mymoona
- Amanie John Oliver
- Ammeter Barb
- Amoaten Thomas
- Amos Claire
- Anderson Beverley
- Anderson Chris
- Anderson Jim
- Anderson John
- Anderson John
- Anderson Juliette
- Anderson Juliette
- Anderson Leanne
- Anderson Naomi
- Anderson Susan
- Anderson Susan
- Andrade Gerard
- Andrews (nee Moore) Eleanor
- Andrews Kelly
- Andrews Stephen
- Ang Daniel
- Ann Taehee
- Annan Lynda
- Ansari Jawaher
- Ansari Jawaher
- Anscombe Eleanor
- Anyamene Nicola
- Appleby Bonny
- Appleby Rowan
- Archer Denise
- Archer Denise
- Archer Simon
- Archer Simon
- Arnott Seonaid
- Arsanious Nasr
- Ashcroft Jan
- Ashworth Sue
- Ashworth Sue
- Askew Sarah
- Aslam Natasha
- Atkinson Jane
- Atkinson Lorraine
- Attlee Julie
- Auladin Raidah
- Austin (nee Glover) Gemma
- Austin Mandy
- Avery Alison
- Avis Joanne
- Aya Viviana
- Azirar Hanna
- Bachand Francois
- Bahary JeanPaul
- Bahl Amit
- Bahl Amit
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- Bailey Linda
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- Balogun Shaki
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- Baria Karin
- Barkati Maroie
- Barkati Maroie
- Barke Nyssa
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- Barnett Christian
- Barnett Debra
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- Barron Claire
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- Bashir Faheem
- Basu Devy
- Bateman Samantha
- Bates Emma
- Batish Cheryl
- Batz Margaret
- Bauman Glenn
- Baumber Shelley
- Baxter Matt
- Bayley Andrew J
- Beamish Neal
- Beaney Katherine
- Beaney Ronald
- Beard Karen
- Beard Karen
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- Beaton Kirsty
- Beattie Louise
- Beauchemin MarieClaude
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- Bech-Nielsen Nanette
- Bech-Nielsen Nanette
- Bedoya Luis Diaz de
- Beech Darren
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- Beesley Katherine
- Beesley Sharon
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- Bell Karen
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- Benson Richard
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- Benton Richard
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- Beresford Mark
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- Berlin Alejandro
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- Bhatnagar Gagan
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- Bird Stephanie
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- Bissa Caterina
- Bissett Donald
- Bisson MarieEve
- Blackwood Geoffrey
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- Blight Kathy
- Blood Paul A
- Bloomfield David
- Bloomfield David
- Bloomfield Mark
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- Brady Joanne
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- Braun Michael W
- Brawley Chris
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- Brown Joanne
- Brown Maggie
- Brown Rebecca
- Brown Richard B
- Brown Richard B
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- Brulinski Patryk
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- Challipalli Amarnath
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- Choudhury Ananya
- Choudhury Ananya
- Chowdhury Amitava D
- Christensen Anne Juel
- Christensen Tine
- Christmas Sallyanne
- Chrystal Melanie
- Chu William
- Chui Amadeus
- Chung Christina
- Chung Hans T
- Chung Peter
- Chung Peter W.M.
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- Churn Mark
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- Clark Diane
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- Clarke Peter
- Clarke Rachael
- Clarke Samantha
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- Clements Mia AnnaMaria
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- Coffin Teresa
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- Cogley Lyn
- Cole Aiden
- Cole David J
- Cole David J
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- Colligan Steve
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- Collins Gerald
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- Conroy Ruth
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- Conway Rachel
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- Cook Adrian D.
- Cook Audrey
- Cook Audrey
- Cook Wendy
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- Cooke Juniebel
- Cooke Peter
- Coomber Kristy
- Coombs Sarah
- Cooper Adele
- Cooper Sophie
- Coppins Helen
- Corbett Thomas B
- Corcoran Sam
- Corderoy Helen
- Cordwell Amanda
- Corkery Danylle
- Corless Rebecca
- Cormack Margaret
- Cornaby Andrew
- Corner Victoria
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- Coyle Catherine
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- Crellin Perric
- Crellin Perric
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- Cross Vanessa
- Cross William R.
- Crossley Lin
- Crowe (nee Hughes) Dawn
- Crowley Claire
- Crundwell M
- Cserbane Anita
- Cuffe Donna
- Cumming Kirsty
- Cunningham Amy
- Curtis Samantha
- Curtis Sandra
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- Dabbs Marianne
- Dahar Nazeer
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- Dalton-Short Ross
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- Danaswamy Patricia
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- Davies Tracey
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- Davison Sue
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- Dawson Elizabeth
- Dawson Louise
- Dawson-Athey Linda
- Dayes Ian S
- De Silva-Minor Shiroma
- Dean Lynsey
- Dearnaley David
- Deenihan Emma
- Degendorfer Sarah
- Dekaj Fatjon
- Dell Gillian
- Dellar Conor
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- Desai Parth
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- Dharmaprasad Soney
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- Dickson Jeanette
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- Dixit Sanjay
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- Dodds David
- Dodge Sister Jan
- Doherty A
- Donaghey Sally
- Donaldson David
- Donnison Michelle
- Douch Emma
- Doughty Victoria
- Dover Serena
- Downs Nichola
- Doyle Kerrie
- Drachenberg Darrel E
- Drakeley Susan
- Drew Ellen
- Drew Mary (Ellen)
- Driscoll Celine
- DSouza David
- Dubey Arbind
- Dubey Arbind
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- Duncan Graeme
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- Dunne Emma
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- Durrant Lisa
- Dymond Harvey
- E Choan
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- Edwards Steve
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- Fallaize Adrian
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- Ferguson Catherine
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- Fielding Bethany
- Fildes Diane
- Finnegan Niall
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- Firth Alexandra
- Firth Alexandra
- Firth Elizabeth
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- Flaherty Jan
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- Forcat Silvia
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- Ford Daniel
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- Ford Victoria
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- Forkes Janet
- Forkes Janet
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- Frankland Helen
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- Gamble Tina
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- Gao Annie
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- Gardiner Fiona
- Garner Victoria
- Garrett Gina
- Garrido-Perez Sandra
- Gauntlett Monica
- Gauthier Isabelle C
- Gearing Jennifer
- George Siny
- GeorgeChayka Danielle
- Geraghty Kerry
- Ghoul Mokhtar
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- Gibbins Jackie
- Gibbins Kate
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- Gibson Sian
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- Gilbert Duncan
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- Ginnelly Helen
- Giovannini Julia
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- Girolametto Carla
- Gladwell Louise
- Gladwish Adam
- Glaholm John
- Glaholm John
- Gleave Martin E
- Glen Hilary
- Glen Tracy
- Glick Daniel
- Goel Roshni
- Goh Chee
- Goh Chee L.
- Golden Sophie
- Goldenberg S Larry
- Goldstein Cindy
- Goldstein Cindy
- Goldsworthy Simon
- Gollapothu Srilakshmi
- Gomez JoseLuis
- Gomez-Marcos Raquel
- Gonzalez Celia
- Gooch Carol
- Goodhind Frances
- Goodsell Josie
- Goodsell Josie
- Goodwin Emma
- Gopaul Darindra
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- Goss Vanessa
- Gough Jessica
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- Gregory Debbie
- Grieve Sylvia
- Griffen Ailsa
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- Yusof Hilawati
- Zafar Waheed
- Zaidi Sadaf
- Zarkar Anjali
- Zarkar Anjali
- Zarkar Anjali M.
- Zaza Khaled O
- Zelley Sarah
- Zeltser Fred
- Zhang Hanbo
- Zhang Tina Wanting
- Zietz Maria
- Zilkha Helene
- Zinck Connie
- Zinyemba Vivian
- Zurakovsky Hilary
- Zwarych Darlene
- Publication venue
- 'Elsevier BV'
- Publication date
- 01/06/2024
- Field of study
Background
Previous evidence indicates that adjuvant, short-course androgen deprivation therapy (ADT) improves metastasis-free survival when given with primary radiotherapy for intermediate-risk and high-risk localised prostate cancer. However, the value of ADT with postoperative radiotherapy after radical prostatectomy is unclear.
Methods
RADICALS-HD was an international randomised controlled trial to test the efficacy of ADT used in combination with postoperative radiotherapy for prostate cancer. Key eligibility criteria were indication for radiotherapy after radical prostatectomy for prostate cancer, prostate-specific antigen less than 5 ng/mL, absence of metastatic disease, and written consent. Participants were randomly assigned (1:1) to radiotherapy alone (no ADT) or radiotherapy with 6 months of ADT (short-course ADT), using monthly subcutaneous gonadotropin-releasing hormone analogue injections, daily oral bicalutamide monotherapy 150 mg, or monthly subcutaneous degarelix. Randomisation was done centrally through minimisation with a random element, stratified by Gleason score, positive margins, radiotherapy timing, planned radiotherapy schedule, and planned type of ADT, in a computerised system. The allocated treatment was not masked. The primary outcome measure was metastasis-free survival, defined as distant metastasis arising from prostate cancer or death from any cause. Standard survival analysis methods were used, accounting for randomisation stratification factors. The trial had 80% power with two-sided α of 5% to detect an absolute increase in 10-year metastasis-free survival from 80% to 86% (hazard ratio [HR] 0·67). Analyses followed the intention-to-treat principle. The trial is registered with the ISRCTN registry, ISRCTN40814031, and ClinicalTrials.gov, NCT00541047.
Findings
Between Nov 22, 2007, and June 29, 2015, 1480 patients (median age 66 years [IQR 61–69]) were randomly assigned to receive no ADT (n=737) or short-course ADT (n=743) in addition to postoperative radiotherapy at 121 centres in Canada, Denmark, Ireland, and the UK. With a median follow-up of 9·0 years (IQR 7·1–10·1), metastasis-free survival events were reported for 268 participants (142 in the no ADT group and 126 in the short-course ADT group; HR 0·886 [95% CI 0·688–1·140], p=0·35). 10-year metastasis-free survival was 79·2% (95% CI 75·4–82·5) in the no ADT group and 80·4% (76·6–83·6) in the short-course ADT group. Toxicity of grade 3 or higher was reported for 121 (17%) of 737 participants in the no ADT group and 100 (14%) of 743 in the short-course ADT group (p=0·15), with no treatment-related deaths.
Interpretation
Metastatic disease is uncommon following postoperative bed radiotherapy after radical prostatectomy. Adding 6 months of ADT to this radiotherapy did not improve metastasis-free survival compared with no ADT. These findings do not support the use of short-course ADT with postoperative radiotherapy in this patient population
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