4 research outputs found
Robust estimation of bacterial cell count from optical density
- Author
- Aarnio Tiu
- Aaron Leow Chung Yong
- Abbas Anser
- Abduraimova Aiganym
- Abraham Doris
- Acar Beliz Leyla
- Acosta Joaquin
- Adler Nina
- Adulyanukosol Natthawut
- Agena Ejouan
- Agena Ethan
- Aggarwal Priya
- Aguirre Adriana Lizeth Rubio
- Ahlgren Christopher
- Ahuja Janvi
- Aizik Dror
- Akbary Mina
- Akinfenwa Akinwumi
- Akingbesote Ngozi D.
- Akova Umut
- Aldo Ferdinan
- Alexopoulos Ioannis
- Allen Lucy
- Alonso Alejandro
- Altarawneh Dina
- Alvarado Andres Benjamin Sanchez
- Ambre Sanika
- Ameziane Annissa
- Amheine Khadija
- Amin Ihya Fakhrurizal
- Amir Sayeda Sakina
- Amstel Chiel van
- An Yongyan
- Anand Nithishwer Mouroug
- Ananthakrishnan Sathvik
- Anderson Karl
- Angel Sagi
- Annem Vidhya
- Anson Chung Tsun Ho
- Anwar Mariam
- Appel Alana
- Araya Lucas
- Armstrong Alexander
- Arora Neha
- Arora Vasu
- Arruda Beck
- Ashwin F Amal Jude
- Astapenka Artur
- Astles Ben
- Astorino Gabe
- Aubry Celine
- Avileli Rebecca
- Azad Mahnaz Sabeta
- Babar Rehmat
- Babu Priyanka
- Badalli Turan
- Badash Lior
- Baichman-Kass Amichai
- Baldwin Geoff S.
- Baltensperger Oliver Andreas
- Bao Guanke
- Bao Minyue
- Baronaite Ugne
- Barrat Leon Michael
- Barrington Seth
- Barshap Alon
- Bartzoka Natalia
- Basu Anubhav
- Basulto Cynthia
- Bath Scott
- Battina Rohith
- Bauersachs Daniel
- Beal Jacob
- Beale Renee
- Beard Eleanor
- Beck Selina
- Becker Evan
- Benavides Samantha Ayde Pena
- Bennis Nicole
- Bete Anna
- Bhatt Darshak
- Bhowmick Shilpa
- Bian Weixin
- Bijman Eline Yafele
- Bindt Felix
- Blas Karla Soto
- Bo Tang
- Boada Yadira
- Boer Meine
- Bohner Ariel
- Borovko Irina
- Bott Amie
- Bouwmeester Susan
- Bowman Kyle
- Boxem Mike
- Boxuan Cheng
- Boyce Kira
- Boyer Jess
- Brasas Valentas
- Brewer Mathew
- Briand William
- Brink Matilda
- Browne Emily
- Buckley-Taylor Russell
- Budhan Stephanie
- Buller Lisa
- Burckhardt Nele
- Burgland Zachary
- Burns Frank
- Burridge Matt
- Burud Hanna Nedreberg
- Buson Felipe Xavier
- Butterfield Tom
- Byagathvalli Gaurav
- Byatt Gabriel
- Byun Sumin
- Caballero Amalia
- Cai Fu
- Cai Niangui
- Caldwell Sarah
- Camacho Yazmin
- Camille Monteil
- Campbell Robert
- Cao Qinhao
- Cao Yixin
- Cao Yuze
- Carrillo Leo
- Carter Jonah
- Casas Alexis
- Castillo Nora Esther Torres
- Castillo Sandra
- Cave John
- Chai Ruochen
- Chamiec-Case Elizabeth
- Chan Janice
- Chan Yuan-Yao
- Chandramouli Priyanka
- Chang Annabel
- Chang Catherine
- Chang Kevin
- Chang Thomas
- Chang Ting-Chen
- Chang Yu-Ci
- Chapman Tyler
- Chater Dounia
- Chau Anthony
- Chavez Benjamin
- Chavez Francisco
- Chehade Ibrahim
- Chen Carmen
- Chen Chih-Chiang
- Chen Ching-Wei
- Chen Janice
- Chen Junhong
- Chen Junyang
- Chen Junyu
- Chen Pei-Hong
- Chen Ryan
- Chen Weixuan
- Chen Yan
- Chen Yi-Cian
- Chen Yifei
- Chen Zhuoyang
- Cheng Cheng
- Cheng Haolun
- Cheng Hsuan
- Cheng Yu-Hong
- Cheng Yu-Hsuan
- Chenxi Liang
- Cherupalla Arjun
- Chi Jordi
- Chi Shumei
- Chiang Jason
- Chiang Woody
- Ching Lai Tsz
- Ching Lam Kai
- Ching Law Hiu
- Ching Luk Hau
- Chinnathambi Sathivel
- Cho Sungwoo
- Choi Lee Sze
- Choi Youngeun
- Chou Ryan
- Chou Ryan
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- Clapper Jude
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- Clerc Valerian
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- Craw Darilyn
- Crispim Larissa de Souza
- Crone Michael Andrew
- Crooijmans Marjolein
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- Crowley Peter
- Cruz Frida
- Cubukcu Hande
- Culfogienis Dylan
- Czekster Clarissa
- Dai Leijie
- Dalangin Rochelin
- Daniel Benjamin
- Daniels Lea
- Das Neves Laura
- Das Diptatanu
- Davis Christina
- De Silva Nimaya
- Deb Shalini S.
- Deepak Kumar S.
- Deibel Emilie
- Dejoie Julianne
- Dejoux Alice
- DeKloe Jackson
- Del Toro Mariano
- Delalez Nicolas
- Delgadillo Sabrina
- Delhomme Jean
- Demchuk Aubrey
- Deng Nian Ruei
- Deng Rui
- Denter Jennifer
- Deshmukh-Reeves Ed
- Despres Philippe C.
- Devi Velvizhi
- Dhaliwal Gurpreet
- Diaz Fernanda
- Ding Shizhi
- Ding Yiming
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- Do Stephanie
- Dogra Arushi
- Dominguez Viana Isabel Perez
- Dong Dongyang
- Dong Haitao
- Dong Jason
- Dong Shan
- Dong Shan
- Dong Shan
- Dong Shangzhi
- Dong Shangzhi
- Doyle David
- Doyle Shannon
- Dube Alexandre
- Dubuc Emilien
- Dunstan Izzy
- Dusseaux Theodore A.
- Dvorkin Steve
- Edelmayer Marco
- Ehrenworth Amy
- Eidloth Franziska
- Eijkens Bruno
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- El Moubayed Yorgo
- Elcin Evrim
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- Elikan Max
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- Elsa Yeung Hoi Lam
- Emilov Kristian
- Espinoza Diego
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- Faidh Mohammed
- Falgenhauer Elisabeth
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- Farny Natalie G.
- Farrell Jennifer
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- Fierro Daniela Olono
- Figueroa Ana Cristina
- Figueroa Jose Arnulfo Juarez
- Fikry Clara
- Filzen Rachael
- Fischer Matthew
- Fitzgerald Kevin
- Fitzgerald Liza
- Flores Vinicius
- Foda Asmaa
- Fong Yuhui Deborah
- Forman Victor
- Frank Stefanie
- Frankel Eva
- Freire Paulo J. C.
- Friedman Yonatan
- Frohlich Lisa
- Fu Wenhan
- Fu Yousi
- Fuentes Ernie
- Fulton Leah
- Fung Ip Ning
- Fung Yam Shing
- Gabrielli Jacopo
- Gahagan Maddison
- Gaitt Tobias
- Gaizauskaite Aukse
- Gallegos Isabella
- Gamoneda Diego
- Gandhi Rishi
- Gao Cecily
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- Garcia Chrismar
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- Garrido Delia
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- Gaudi Alex
- Ge Gao
- Ge Yubin
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- Gerard Antoine
- Gershater Markus
- Ghosh Souvik
- Giannopoulos Alexandros Dimitriou
- Giannoula Yvoni
- Gilman Daniel Barber James
- Glockner Eleanor
- Goenka Anushya
- Goetz Marley
- Gogineni Namrata
- Gokul [NO FIRST NAME IN SCOPUS]
- Gonzalo Gonzalo Saiz
- Goodson Michael
- Gopaul Deshmukh
- Gou Yanchen
- Govers Jolijn
- Graaf Floor de
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- Graves Daniel
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- Shuan Yun
- Shulun [NO FIRST NAME IN SCOPUS]
- Shuyu Shi
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- Tairan Li
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- Zukauskaite Kristina
- Zulueta Patricia
- Zvirblyte Justina
- Publication venue
- Publication date
- 01/01/2020
- Field of study
Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data
Sparsentan in patients with IgA nephropathy: a prespecified interim analysis from a randomised, double-blind, active-controlled clinical trial
- Author
- Aaron Fearday
- Abdallah Geara
- Adam Morris
- Adriana Fernandes
- Adriana Sierra Ochoa
- Aejin Kim
- Agata Winiarska
- Aine Maire De Bhailis
- Ajay Dhaygude
- Alastair Gillies
- Alba Atenza
- Alberto Ortiz Arduan
- Alejandro Soria Villen
- Alessia Fornoni
- Alex Mercer PhD g
- Alexandre Buffet
- Alexandre Karras
- Alfred Rodriguez
- Ali Assefi
- Allister Williams
- Allyson Medina
- Alvaro Vaz
- Alvita Vickiene
- Amanda Hall
- Amanda Mather
- Amanda Siriwardana
- Amar Mahdi
- Amy Henderson
- Amy Hudson
- An Vanacker
- Ana Avila Bernabeu
- Ana Carolina Figueiredo
- Ana Cortesão Costa
- Ana Farinha
- Ana Marta Gomes
- Ana Messias
- Ana Natario
- Ana Perez de Jose
- Ana Savuk
- Ana Vilar Gimeno
- Andrea Cavalli
- Andrea Solazzo
- Andrew Bomback
- Andrew Henderson
- Andrew McNally
- Angel Forcen
- Angel Sevillano
- Angus Ritchie
- Angus Turnbull
- Anna Benesova
- Anna Jander
- Anna Ricchiuto
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- Anne-Elisabeth Heng
- Annegret Koch
- Annette Girardet
- Annie Reynolds
- Annika Adoberg
- Anoushka Krishnan
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- Arksarapuk Jittirat
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- Yen-Ling Chiu
- Yeong Hoon Kim
- Yi-Wen Chiu
- Yick Hei Wong
- Yonatan Peleg
- Young Rim Song
- YoungYoul Hyun
- Yu-Sen Peng
- Yunmi Kim
- Yusuf Eqbal
- Yusuf Eqbal
- Yvonne Shen
- Zivka Dika
- Zoltan Endre
- Zvonimir Sitas
- Publication venue
- Publication date
- 01/01/2023
- Field of study
Background: Sparsentan is a novel, non-immunosuppressive, single-molecule, dual endothelin and angiotensin receptor antagonist being examined in an ongoing phase 3 trial in adults with IgA nephropathy. We report the prespecified interim analysis of the primary proteinuria efficacy endpoint, and safety. Methods: PROTECT is an international, randomised, double-blind, active-controlled study, being conducted in 134 clinical practice sites in 18 countries. The study examines sparsentan versus irbesartan in adults (aged ≥18 years) with biopsy-proven IgA nephropathy and proteinuria of 1·0 g/day or higher despite maximised renin-angiotensin system inhibitor treatment for at least 12 weeks. Participants were randomly assigned in a 1:1 ratio to receive sparsentan 400 mg once daily or irbesartan 300 mg once daily, stratified by estimated glomerular filtration rate at screening (30 to 1·75 g/day). The primary efficacy endpoint was change from baseline to week 36 in urine protein-creatinine ratio based on a 24-h urine sample, assessed using mixed model repeated measures. Treatment-emergent adverse events (TEAEs) were safety endpoints. All endpoints were examined in all participants who received at least one dose of randomised treatment. The study is ongoing and is registered with ClinicalTrials.gov, NCT03762850. Findings: Between Dec 20, 2018, and May 26, 2021, 404 participants were randomly assigned to sparsentan (n=202) or irbesartan (n=202) and received treatment. At week 36, the geometric least squares mean percent change from baseline in urine protein-creatinine ratio was statistically significantly greater in the sparsentan group (-49·8%) than the irbesartan group (-15·1%), resulting in a between-group relative reduction of 41% (least squares mean ratio=0·59; 95% CI 0·51-0·69; p<0·0001). TEAEs with sparsentan were similar to irbesartan. There were no cases of severe oedema, heart failure, hepatotoxicity, or oedema-related discontinuations. Bodyweight changes from baseline were not different between the sparsentan and irbesartan groups. Interpretation: Once-daily treatment with sparsentan produced meaningful reduction in proteinuria compared with irbesartan in adults with IgA nephropathy. Safety of sparsentan was similar to irbesartan. Future analyses after completion of the 2-year double-blind period will show whether these beneficial effects translate into a long-term nephroprotective potential of sparsentan. Funding: Travere Therapeutics
Efficacy and safety of sparsentan versus irbesartan in patients with IgA nephropathy (PROTECT): 2-year results from a randomised, active-controlled, phase 3 trial
- Author
- Aaron Fearday (17386231)
- Abdallah Geara (17386297)
- Adam Morris (2043517)
- Adriana Fernandes (8856416)
- Adriana Sierra Ochoa (17386699)
- Aejin Kim (2175798)
- Agata Winiarska (17387086)
- Aine Maire De Bhailis (17386168)
- Ajay Dhaygude (10682946)
- Alastair Gillies (17386309)
- Alba Atenza (17385991)
- Alberto Ortiz Arduan (17385973)
- Alejandro Soria Villen (17387041)
- Alessia Fornoni (519467)
- Alex Mercer (59669)
- Alexandre Buffet (14930766)
- Alexandre Karras (506611)
- Alfred Rodriguez (17386840)
- Ali Assefi (17385988)
- Allister Williams (17387083)
- Allyson Medina (17386612)
- Alvaro Vaz (17387023)
- Alvita Vickiene (6473255)
- Amanda Hall (210816)
- Amanda Mather (285324)
- Amanda Siriwardana (17386933)
- Amar Mahdi (10295868)
- Amy Henderson (17386369)
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- Rathika Krishnasamy (739909)
- Raul Fernandez Prado (17386801)
- Richard Lafayette (16914378)
- Rishi Pruthi (13042917)
- Ritesh Raichoudhury (9909222)
- Robert Carroll (9442)
- Robert Davidson (1837861)
- Robert Haws (17386363)
- Robert Malecki (3433673)
- Robert Małecki (17385910)
- Roberta Aliotta (17385955)
- Rocco Baccaro (17386009)
- Roderick Comunale (17386150)
- Roger Wyndham (17387101)
- Rouzbeh Afsari (17385934)
- Roxane Gaisset (17386282)
- Rui Barata (10873253)
- Sadia Jahan (12758567)
- Saif Al Chalabi (17385952)
- Salem Almaani (17385958)
- Salia Virxinia Pol Heres (17386375)
- Sam Daneshvari (17386162)
- Samir Parikh (5594378)
- Sandra Karanovic (17386441)
- Sang-Kyung Jo (442610)
- Sapna Shah (579169)
- Sara Fernandes (3121533)
- Sara Goncalves (17386336)
- Sara Ombelet (17386708)
- Sara Vigano (17387029)
- Sarah Ashley (14954712)
- Sarah Lawman (9758498)
- Sarah Quinn (17094908)
- Sarah Roxburgh (17386852)
- Saravanan Balamuthusamy (467385)
- Se Joong Kim (13205663)
- Se Won Oh (9338439)
- Sebahat Sat (17386885)
- Secundino Cigarran Guldris (17386354)
- Selena Longhi (412597)
- Serena Ponti (17386795)
- Seung Hyeok Han (8976257)
- SeWon Oh (17386702)
- Shamik Bhadra (17386039)
- Shang-Feng Tsai (8251905)
- Shang-Jyh Hwang (5312)
- Sharon Adler (3404507)
- Shaundeep Sen (121125)
- Sheng Kuo (17386492)
- Shih-Hsiang Ou (2832815)
- Shih-Ping Hsu (315722)
- Shilpanjali Jesudason (17386417)
- Sian Griffin (8401269)
- Siddhartha Kattamanchi (15358922)
- Silja Sanden (17386867)
- Silvia Malvica (17386573)
- Simon Mucha (6437372)
- Simon Roger (3661408)
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- Simone Kulka (17386489)
- Siu Fai Cheung (17386114)
- Smeeta Sinha (4847929)
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- Sofie Jamar (5331284)
- Songuk Yoon (17387113)
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- Sreedhar Mandayam (9623752)
- Stacy Martinez (8620377)
- Stefan Weiner (17387068)
- Stefanie Stangenberg (8991251)
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- Susan Crail (6164591)
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- Thu Nguyen (2179258)
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- Tomasz Stompor (3433691)
- Tung-Min Yu (546163)
- Tze Goh (17386321)
- Tzung-Yo Ho (7337477)
- Ulrich Kunzendorf (5780207)
- Ulysses A Diva (17385901)
- Unnikrishnan Pillai (17386783)
- Ursula Verdalles Guzman (17386357)
- Urte Zakauskiene (17387122)
- Usha Peri (17386777)
- Valentin Mayet (17386597)
- Valérie de Précigout (17386171)
- Veronica Viramontes (17387044)
- Victor Fernandez (17386243)
- Victoria Campbell (239881)
- Vidu Wijeratne (17387077)
- Viet Nguyen (79713)
- Vittoria Esposito (5787344)
- Vladimir Tesar (156920)
- Vlado Perkovic (141532)
- Wai Lim (3583598)
- Wai Ping Law (12288571)
- Wan-Chuan Tsai (5476856)
- Wanja Bernhardt (245782)
- Wenceslao Adrian Aguilera Morales (17386651)
- William E Rote (17385919)
- William Paxton (17386750)
- Wim Lemahieu (3547811)
- Wladyslaw Sulowicz (17386969)
- Wooin Ahn (17385943)
- Wookyung Chung (610342)
- Xavier Warling (17387056)
- Yahsou Delmas (4034183)
- Yan Li (23143)
- Yelena Drexler (12365018)
- Yen-Ling Chiu (442530)
- Yeong Hoon Kim (8962688)
- Yi-Wen Chiu (106535)
- Yick Hei Wong (12288568)
- Yonatan Peleg (9922071)
- Young Rim Song (13242926)
- Young Youl Hyun (13016397)
- Yu-Sen Peng (315725)
- Yunmi Kim (3040866)
- Yusuf Eqbal (17386222)
- Yvonne Shen (17386921)
- Zivka Dika (10281479)
- Zoltan Endre (714028)
- Zvonimir Sitas (17386936)
- Publication venue
- Publication date
- 01/12/2023
- Field of study
Background
Sparsentan, a novel, non-immunosuppressive, single-molecule, dual endothelin angiotensin receptor antagonist, significantly reduced proteinuria versus irbesartan, an angiotensin II receptor blocker, at 36 weeks (primary endpoint) in patients with immunoglobulin A nephropathy in the phase 3 PROTECT trial's previously reported interim analysis. Here, we report kidney function and outcomes over 110 weeks from the double-blind final analysis.
Methods
PROTECT, a double-blind, randomised, active-controlled, phase 3 study, was done across 134 clinical practice sites in 18 countries throughout the Americas, Asia, and Europe. Patients aged 18 years or older with biopsy-proven primary IgA nephropathy and proteinuria of at least 1·0 g per day despite maximised renin–angiotensin system inhibition for at least 12 weeks were randomly assigned (1:1) to receive sparsentan (target dose 400 mg oral sparsentan once daily) or irbesartan (target dose 300 mg oral irbesartan once daily) based on a permuted-block randomisation method. The primary endpoint was proteinuria change between treatment groups at 36 weeks. Secondary endpoints included rate of change (slope) of the estimated glomerular filtration rate (eGFR), changes in proteinuria, a composite of kidney failure (confirmed 40% eGFR reduction, end-stage kidney disease, or all-cause mortality), and safety and tolerability up to 110 weeks from randomisation. Secondary efficacy outcomes were assessed in the full analysis set and safety was assessed in the safety set, both of which were defined as all patients who were randomly assigned and received at least one dose of randomly assigned study drug. This trial is registered with ClinicalTrials.gov, NCT03762850.
Findings
Between Dec 20, 2018, and May 26, 2021, 203 patients were randomly assigned to the sparsentan group and 203 to the irbesartan group. One patient from each group did not receive the study drug and was excluded from the efficacy and safety analyses (282 [70%] of 404 included patients were male and 272 [67%] were White) . Patients in the sparsentan group had a slower rate of eGFR decline than those in the irbesartan group. eGFR chronic 2-year slope (weeks 6–110) was −2·7 mL/min per 1·73 m2 per year versus −3·8 mL/min per 1·73 m2 per year (difference 1·1 mL/min per 1·73 m2 per year, 95% CI 0·1 to 2·1; p=0·037); total 2-year slope (day 1–week 110) was −2·9 mL/min per 1·73 m2 per year versus −3·9 mL/min per 1·73 m2 per year (difference 1·0 mL/min per 1·73 m2 per year, 95% CI −0·03 to 1·94; p=0·058). The significant reduction in proteinuria at 36 weeks with sparsentan was maintained throughout the study period; at 110 weeks, proteinuria, as determined by the change from baseline in urine protein-to-creatinine ratio, was 40% lower in the sparsentan group than in the irbesartan group (−42·8%, 95% CI −49·8 to −35·0, with sparsentan versus −4·4%, −15·8 to 8·7, with irbesartan; geometric least-squares mean ratio 0·60, 95% CI 0·50 to 0·72). The composite kidney failure endpoint was reached by 18 (9%) of 202 patients in the sparsentan group versus 26 (13%) of 202 patients in the irbesartan group (relative risk 0·7, 95% CI 0·4 to 1·2). Treatment-emergent adverse events were well balanced between sparsentan and irbesartan, with no new safety signals.
Interpretation
Over 110 weeks, treatment with sparsentan versus maximally titrated irbesartan in patients with IgA nephropathy resulted in significant reductions in proteinuria and preservation of kidney function.</p
Open data from the first and second observing runs of Advanced LIGO and Advanced Virgo
- Author
- David E.
- Jo F. J.
- Karl
- Loic
- Marc
- Nathan A.
- Romain
- Shreya
- a R.
- a Pratap K.
- Abbott Rich
- Abbott Thomas D.
- Abraham Sheelu
- Acernese Fausto
- Ackley Kendall
- Adams Carl
- Adhikari Rana X.
- Adya Vaishali B.
- Affeldt Christoph
- Agathos Michalis
- Agatsuma Kazuhiro
- Aggarwal Nancy
- Aguiar Odylio D.
- Aich Amit
- Aiello Lorenzo
- Ain Anirban
- Allen Gabrielle
- Allocca Annalisa
- Altin Paul A.
- am Manasadevi P.
- Amato Alex
- An
- Ananyeva Alena
- Anderson Stuart B.
- Anderson Warren G.
- Angelova
- Ankit
- Ansoldi Stefano
- Antier Sarah
- Appert Stephen
- Arai Koji
- Araya Melody C.
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- Areeda Joseph S.
- Arene Marc
- ari
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- Arnaud Nicolas
- Aronson Scott M.
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- Ascenzi Stefano
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- Astone Pia
- Aubin Florian
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- Zadrozny Adam
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- Zanolin Michele
- Zelenova Tatiana
- Zendri Jean-pierre
- Zevin Michael
- Zhang Jue
- Zhang Liyuan
- Zhang Teng
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- Zimmerman Aaron B.
- Zucker Michael E.
- Zweizig John
- Publication venue
- 'Elsevier BV'
- Publication date
- 25/12/2019
- Field of study
Advanced LIGO and Advanced Virgo are monitoring the sky and collecting gravitational-wave strain data with sufficient sensitivity to detect signals routinely. In this paper we describe the data recorded by these instruments during their first and second observing runs. The main data products are gravitational-wave strain time series sampled at 16384 Hz. The datasets that include this strain measurement can be freely accessed through the Gravitational Wave Open Science Center at http://gw-openscience.org, together with data-quality information essential for the analysis of LIGO and Virgo data, documentation, tutorials, and supporting software