text:
MONSTER TWIST PARTY: CAT fundraiser 6-9 p.m. today at Community Access Television, 101 W. Rock St. in Fayetteville. Games, dancing, contests. 444-3433.
HALLOWEEN STORYTIME: 6:30 p.m. today at the Fayetteville Public Library. Free; for preschooler; costumes encouraged. faylib.org or 856-7170.
HALLOWEEN COSTUME PARTY: 10 a.m. Friday at the Fayetteville Senior Center, 945 S. College. Games, prizes and candy. 571-2920.
TRICK OR TREAT ON THE SQUARE: 3-5 p.m. Friday around the downtown square in Fayetteville. Candy, games, pictures, costume and pet contests. 521-5776.
GOBLIN PARADE: 3:15-5 p.m. Friday at Frisco Park in Rogers. Free family friendly trick-or-treat event in downtown Rogers. mainstreetrogers.com or 936-5487.
OLD SPANISH TREASURE HAUNTED CAVE: 7 p.m. today, Friday and Saturday near Gravette. $9-$18. 787-6508.
NIGHTMARES HAUNTED HOUSE: 7-11 p.m. Friday and Saturday in Bella Vista. Hauntednightmares.com for directions. $5-$10.
THE OXFORD AMERICAN: Music edition launch benefit and party at 8 p.m. Saturday at the U-ARK Bowl, 644 W. Dickson St. in Fayetteville. Music by Ocie Fisher & The Hipp Dogs. $50 at the door or at Sound Warehouse, oxfordamericanmag.com or 501-450-5376.
OMNI CENTER: Demonstration for U.S. troop withdrawal from Iraq at 1 p.m. Saturday at the corner of Mall Avenue and Joyce Boulevard in Fayetteville. Signs provided. Follow up demonstrations first Saturdays of the month at this location. makejobsnotwars.com or 586-2053.
OZARKS FOLK FESTIVAL: Nov. 6-9 in Eureka Springs. With Noah Earle, Greg Klyma, Parry Larkin and Vagabond Van. Songwriting contest Nov. 8 at Basin Park. Some events free, some with a fee. ozarkfolkfestival.com or 888-855-7823.
INGRID GIPSON: artist's reception from 5-7 p.m. Nov. 6 at Arsaga's, 1582 Crossover, Ste. 2 in Fayetteville. arsagas.org or 527-0690.
FILM "CARIBBEAN JEWELS": 1 p.m. today at the Arts Center of the Ozarks in Springdale. $9-$10. artscenteroftheozarks.org or 751-5441.
"STOP KISS": 8 p.m. today through Saturday, and 2 p.m. Sunday at the University Theatre, 228 Fine Arts Center in Fayetteville. Directed by Emily Jones. $14. 575-4752.
"SORRY THE BRIDGE IS OUT, YOU'LL HAVE TO STAY THE NIGHT": 7:30 p.m. Friday and Saturday at the Arts Center of the Ozarks in Springdale. $9-$20. artscenteroftheozarks.org or 751-5441.
JUNGLE JACK HANNA: 3 p.m. Saturday at the Walton Arts Center in Fayetteville. $15-$25. waltonartscenter.org or 443-5600.
FIRST LADY GINGER BEEBE: 1-3 p.m. today for a book signing at Crystal Bridges at the Massey. crystalbridges.org or 418-5700.
TRENTON LEE STEWART: 10 a.m. and 11 a.m. Saturday at the Fayetteville Public Library. Registration required for the 10 a.m. breakfast. nightbirdbooks.com or 443-2080.
STEVEN FOSTER & CYNTHIA GALLAHER: will speak on herbs at 6:30 p.m. Saturday at Fire Om Earth Studio, 874 Mill Hollow Rd. in Eureka Springs. $10. fireomearth.com
OMNI'S OPEN MIC FOR PEACE: 7 p.m. Sunday at Nightbird Books. With Dan Dean. nightbirdbooks.com or 582-2291.
JOHN PARKS: Percussion recital at 8 p.m. today at University of Arkansas Fine Arts Concert Hall. Free. 575-4701.
SPOOKSTOCK 7: Friday and Saturday at Camp Zoe in Salem, Mo. Chicago Afrobeat Project, The Schwag, Down Lo, Shattermask, Tiffany Christopher, Jaik Willis, DJ Cypher and a Soulshine Liquid Art lightshow. $50-$60. campzoe.com or 573-858-3333.
FLYING TOMATO CABARET: at 7 p.m. Friday through Sunday and Nov. 7-9 at NWACC Shewmaker Center in Bentonville. Spaghetti dinner with waiters singing from Rent, Chicago, Evita and other Broadway hits. $15; reservations required. scooper@nwacc.edu or 619-4261.
SONGWRITERS IN THE ROUND: 9 p.m. Friday at Arsaga's Gregg, 2418 N. Gregg Ave. in Fayetteville. Jim Patton, Sherry Brokus, Effron White and Reese Neal. arsagas.com or 444-6557.
GUY WILCOX: Voice recital at 4 p.m. Sunday at University of Arkansas Fine Arts Concert Hall. Free. 575-4701.
JOEL SCHISLER: Guitar recital: 7 p.m. Sunday at University of Arkansas Fine Arts Concert Hall. Free. 575-4701.
UA PERCUSSION ENSEMBLE: 8 p.m. Monday at the Walton Arts Center in Fayetteville. $1-$10. waltonartscenter.org or 443-5600.
JANICE YOES: Voice recital at 7:30 p.m. Tuesday at University of Arkansas Fine Arts Concert Hall. Free. 575-4701.
LYRIQUE QUINTET: 8 p.m. Wednesday at University of Arkansas Fine Arts Concert Hall. Free. 575-4701.
KELLY HENDERSON: Oboe recital at 7 p.m. Nov. 6 at University of Arkansas Fine Arts Concert Hall. Free. 575-4701.
"CLAY & CROCHET" WORKSHOP: 1:30 p.m. today and Friday, LECTURE: 5 p.m. today. Events on the University of Arkansas campus. Call 575-7987.
DRESS UP AND DANCE: 8 and 9 p.m. Fridays at Teatro Scarpino in Fayetteville. $10. scarpino.com or 409-3772.
SOUTHWEST SERVICE DOGS: 1 p.m. Saturday at the Jones Center in Springdale. Free; demonstration of service dogs. southwestservicedogs.org or 646-0886.
LATIN AMERICAN SOCIAL ENTREPRENEURS: Discussion with Gladys Tiffany at 2 p.m. Sunday and panel discussion on Trade and Agriculture at 7 p.m. Wednesday at the Fayetteville Public Library. Free. faylib.org or 856-7250.
GREENDRINKS: 5:30 p.m. Wednesday at Smiling Jack's, 262 N. School Ave. in Fayetteville. Organized by a coalition of Northwest Arkansas environmental groups. 225-2077.
COMMUNITY BIBLE STUDY: 9:15 a.m. Wednesdays at the Jones Center for Families. 601-4984.
BUDDHIST MEDITATION: 7:30 p.m. Thursdays at the Arkansas Yoga Center in Fayetteville. 422-6526.
A COURSE IN MIRACLES: 7:30 p.m. Thursdays at Unity of Fayetteville. unityfay.org or 442-0680.
DHARMA TALK: 11 a.m. Sundays at Dramis Hardwood Floors, 2275 S. School Ave. in Fayetteville. With Tibetan Buddhist Monk Ven. Geshe Thupten Dorjee. tcia.com or 587-8920.
STILL MIND MEDITATION: 9 p.m. Sundays at the School of Metaphysics in Fayetteville. som.org or 527-6804.
RAZORBACKS VS. TULSA: 1 p.m. Saturday in Fayetteville. Razorback Homecoming. arkansasrazorbacks.com.
FAYETTEVILLE FARMERS' MARKET: 7 a.m. Saturdays through Nov. 22 on the Fayetteville Square. Holiday items available. fayettevillefarmersmarket.org or 236-2910.
YOUTHCAN! FAMILY DAY: 10 a.m. to 4 p.m. Saturday at Community Imagination Studio, 818 N. Sang Ave. in Fayetteville. Free; no pre-registration. communityimaginationstudio.org or 442-8585.
FAMILY SATURDAYS: 11 a.m.-1 p.m. Saturdays at the Northwest Arkansas Community Creative Center in Fayetteville. For ages 4 and up; $10 per child. nwaccc.org or 927-2491.
TRIKE NIGHT LIVE: 8:30 p.m. Saturday at Tricycle Theatre, 120 S. Main St. in Bentonville. $5; family friendly open mic event for teens. triketheatre.org or 888-331-3681.
TRICYCLE THEATRE NOVEMBER CLASSES: Monday at Tricycle Theatre, 120 S. Main St. in Bentonville. Times, ages, days, and costs vary. triketheatre.org or 888-331-3681.
ENTRIES SOUGHT FOR COMMUNITY CHRISTMAS PARADE: A ROGERS CHRISTMAS STORY: Applications due 4 p.m. Nov. 7 to 301 W. Chestnut in Rogers. Parade at 7 p.m. Dec. 1. mainstreetrogers.com or 936-5487.
"A MURDER ANNOUNCED" AUDITION: 7:30 p.m. Dec. 15-16 at the Arts Center of the Ozarks in Springdale. artscenteroftheozarks.org 751-5441.
ANNE KITTRELL ART GALLERY: Arkansas Union, Fayetteville. 575-5255. Fayetteville Four Fall Show through Saturday.
ARSAGA'S: 1582 Crossover Road, Fayetteville. arsagas.org or 527-0690. Sculptural masks by Ingrid Gipson Saturday through November.
ARSAGA'S: 2418 N. Gregg Ave., Fayetteville. arsagas.org or 444-6557. Paintings on metal by Greg Moore through November.
THE COMMON GROUNDS: 412 W. Dickson St., Fayetteville. commongroundsar.com or 442-3515. Paintings and photographs by Steve Adair, LaDonna Shub and Courtney Knieff through December.
CRYSTAL BRIDGES AT THE MASSEY: 125 W. Central Ave., Bentonville. massey.crystalbridges.org or 418-5700. "Formulation: Articulation" by Josef Albers through Dec. 27.
DDP GALLERY: 7 E. Mountain St., Fayetteville. ddpgallery.com or 442-0001. "A Taxonomy of Wounds" by Amjad Faur and "Noctilucent" by Preston Graves through Nov. 22.
FOUR SQUARE FINE ART GALLERY: 112 W. Center St., Fayetteville. FourSquareFineArt.com or 422-8607. "Things Remembered, Things Forgotten" by Tanya Johnston through Nov. 15.
JULIE WAIT DESIGNS ART GALLERY: 318 S. First St., Rogers. juliewaitdesigns.com or 631-8706. Jan Ironside through October.
RICHLAND NURSERY AND ART GALLERY: Hwy 23 South, Huntsville. 738-5305.
TERRA STUDIOS, MUSE GALLERY & COFFEE HOUSE: 12103 Hazel Valley Road, off Hwy 16E in Durham. terrastudios.com or 1-800-255-8995. Featuring art work by over 30 artists, 10 acres of gardens in the Art Park with murals and sculpture installations. Home of the Original Bluebird of Happiness. Raku and Stoneware pottery by Maura Miller through October.
UNIVERSITY OF ARKANSAS FINE ARTS CENTER GALLERY: Fayetteville. 575-7987. Arkansas Arts Council's Small Works on Paper 2008 Monday through Nov. 26.
WALTON ARTS CENTER: 495 W. Dickson St., Fayetteville. waltonartscenter.org or 443-5600. "Slow Dancing" by David Michalek through Nov. 13.
ARKANSAS ARTS CENTER: Ninth and Commerce Streets, Little Rock. arkarts.com or (501)372-4000. " Andy Warhol: 15 Weeks of Fame" through Feb. 1. "Building the Collection: Rackstraw Downes" through Dec. 7. "51st Annual Delta Exhibition" through Nov. 16. "Visions: Selection from the James T. Dyke Collection of Contemporary Drawings" through Nov. 9.
PRICE TOWER ARTS CENTER: 510 Dewey Ave., Bartlesville, OK. pricetower.org or 877-424-2424. "3-ology Triennial 2008: Imaginative Qualities of Actual Things" through Jan. 4.
ROGERS HISTORICAL MUSEUM: 322 S. Second St., Rogers. 621-1154. rogersarkansas.com/museum. "Down a Lazy River: Float Fishing on the White River" through December.
SILOAM SPRINGS MUSEUM: 112 N. Maxwell St., 524-4011. "Collector's Collections" Wednesday through Jan. 14.
ROBERT GLICK ARTIST'S RECEPTION: 4 p.m. Nov. 7 at Julie Wait Designs Art Gallery, 318 S. First St. in Rogers. juliewaitdesigns.com or 631-8706.
THE JOEY DEFRANCESCO TRIO: 7 p.m. and 9:30 p.m. Nov. 7 at the Walton Arts Center in Fayetteville. $15-$30. waltonartscenter.org or 443-5600.
UA MASTER CHORALE AND SCHOLA CANTORUM "FAURE REQUIEM": 8 p.m. Nov. 7 at the Walton Arts Center in Fayetteville. $10. waltonartscenter.org or 443-5600.
"YOU CAN'T TAKE IT WITH YOU": 8 p.m. Nov. 7-8 and Nov. 14-15 and Nov. 20-22, and 2 p.m. Nov. 16 and Nov. 23 at the Rogers Little Theater. $7.50-$42. RogersLittleTheater.com or 631-8988.
"ANNE OF GREEN GABLES": 3 p.m. Nov. 8-9 at the Arts Center of the Ozarks in Springdale. $8-$16. artscenteroftheozarks.org or 751-5441.
"THE UNIVERSE OF JAMES YALE" EXHIBIT AND ARTISTS RECEPTION: 6-9 p.m. Nov. 8 at The Eureka Fine Art Company, 78 Spring St. in Eureka Springs. 253-6595.
UA INSPIRATIONAL SINGERS: 7:30 p.m. Nov. 8 at the Walton Arts Center in Fayetteville. $10. waltonartscenter.org or 443-5600.
PAVLO: 2 p.m. Nov. 9 at Arend Arts Center, 1901 S.E. J St. in Bentonville. $5-$25. bentonville.k12.ar.us/arendarts or 855-1968.
MELANIE SAFKA: 2 p.m. Nov. 9 at the AUD in Eureka Springs. theaud.com or 253-7788.
UA WIND SYMPHONY & SYMPHONY ORCHESTRA "DESTINY": 7:30 p.m. Nov. 10 at the Walton Arts Center in Fayetteville. $10. waltonartscenter.org or 443-5600.
O.A.R. JONATHAN TAYLOR AND NORTHERN LIGHTS: 8 p.m. Nov. 10 at Barnhill Arena in Fayetteville. $25. ticketmaster.com or 575-6785.
EMPTY BOWLS: 6-9 p.m. Nov. 11 at George's on Dickson Street in Fayetteville. Benefits NWA Food Bank. Live music by Shack. $20-$25; includes simple gourmet soup dinner and handmade bowl. For more contact Kelly Wilks at flatrockclay.com or 521-3181.
OZARK POETRY SLAM: 7 p.m. Nov. 11 at Smiling Jack's in Fayetteville. $5 cover. Cash Money Slam; all ages, no ill-behaved children. 466-6006.
UA RAZORBACK BAND SPECTACULAR: 7:30 p.m. Nov. 11 at the Walton Arts Center in Fayetteville. $10. waltonartscenter.org or 443-5600.
BALLET MASTER CLASS WITH LES GRANDS BALLET CANADIENS DE MONTREAL: 5:30 p.m. Nov. 12 at the Walton Arts Center in Fayetteville. $25. waltonartscenter.org or 443-5600.
ART AMISS 9: Nov. 13 at the Dickson Theatre in Fayetteville. artamiss.org.
LES GRANDS BALLET CANADIENS DE MONTREAL: 7 p.m. Nov. 13 at the Walton Arts Center in Fayetteville. $18-$30. waltonartscenter.org or 443-5600.
"PEARL'S SIXTH WEDDING": 8 p.m. Nov. 14-15 at St. Paul's Episcopal Church, 224 N. East St. in Fayetteville. Featuring beloved characters from the "Dupont, Mississippi" series. $17-$20. Includes reception following show. 571-4879.
ANTIQUE SHOW & SALE: Nov. 15-16 at the Inn of the Ozarks in Eureka Springs. eureakspringsantiqueshow.com or 253-7551.
SILENT AUCTION: noon-4 p.m. Nov. 15 at the Fayetteville Public Library. Supports Friends of the Fayetteville Public Library. faylib.org or 856-7140.
NWA ART EXHIBITION ARTISTS' RECEPTION: 5:30-7 p.m. Nov. 15 at the Arts Center of the Ozarks, 214 S. Main St. in Springdale. artscenteroftheozarks.org or 751-5441.
BOB & TOM COMEDY ALL-STARS: 7:30 p.m. Nov. 15 at the Walton Arts Center in Fayetteville. $31.50. waltonartscenter.org or 443-5600.
SWEENEY TODD: THE DEMON BARBER OF FLEET STREET: 7 p.m. Nov. 17-18 at the Walton Arts Center in Fayetteville. $42-$50. waltonartscenter.org or 443-5600.
GREG MOORE ARTIST'S RECEPTION: 7-9 p.m. Nov. 20 at Arsaga's, 2418 N. Gregg Ave. in Fayetteville. arsagas.org or 444-6557. Paintings on metal by Greg Moore Saturday through November.
SARAH CREASMAN RECEPTION: Nov. 21 at the Rogers Little Theatre, 116 S. Second St., in Rogers. RogersLittleTheater.com or 631-8988.
"PUSS IN BOOTS": 3 p.m. Nov. 22 at the Arts Center of the Ozarks in Springdale. $8-$16. artscenteroftheozarks.org or 751-5441.
PUNCH BROTHERS FEATURING CHRIS THILE: 8 p.m. Nov. 22 at the Walton Arts Center in Fayetteville. $18-$28. waltonartscenter.org or 443-5600.
ACO CHORALE "HOLIDAY IN MUSIC CONCERT": 3 p.m. Nov. 23 at the Arts Center of the Ozarks in Springdale. $4-$8. artscenteroftheozarks.org or 751-5441.
SANTA IN THE PARK: Nov. 28 at Basin Park in Eureka Springs. eurekaspringschamber.com.
FALL ART SHOW: 9 a.m.-7 p.m. Nov. 29 and 9 a.m. -3 p.m. Nov. 30 at the Inn of the Ozarks Convention Center in Eureka Springs. 253-5826.


text:
Commerce and collecting
An extract from the Trade and Empire exhibition at The Whitworth Art Gallery
Slave-grown cotton is key to the story of the Industrial Revolution and to the accumulation of wealth that built Manchester during the eighteenth and nineteenth centuries. Every ounce of cotton in Britain was imported from overseas plantations, many of which used enslaved labour.
During the eighteenth century the slave plantations of the West Indies provided Manchester with raw cotton alongside the traditional sources of the Middle East and India. From 1790 this shifted to a dependence on the slave plantations of the American south and by 1802 America had become the largest supplier of cotton to the British market.
Slavery continued in North America after the abolition of the British slave trade in 1807 and Manchester remained dependent on slave-grown cotton. As late as 1860 America supplied 88% of the cotton imported into Britain. Slavery enabled cotton to be grown cheaply and was a major reason why the price of cotton textiles fell steadily from the 1790s to 1840.
During the eighteenth and nineteenth centuries new generations of rich industrialists and other businessmen emerged whose wealth derived from businesses associated with cotton. These families used some of this wealth to make collections of fine and decorative art to demonstrate their prestige, refinement and taste.
This map shows the major trade routes operating between Europe, Africa and the Americas, moving enslaved peoples, raw cotton and manufactured goods between the three continents. During the eighteenth and early nineteenth centuries the shape of these trade routes was roughly triangular.
Cotton was crucial to the rise of industrial Manchester but at what cost? An estimated 12 million Africans were forcefully transported across the Atlantic into slavery. Enslaved people were denied basic human rights and the inhumane treatment experienced on slave ships and plantations cost many their lives.
In Manchester, the rise of the cotton industry meant that the population of the city spiralled; multiplying from 17,000 to 180,000 between 1760 and 1830. Living and working conditions were crowded, dirty and dangerous. Whilst some grew very rich through cotton, it caused great deprivation and hardship for many more.
Slave whip
Supplies for European demands
Triangular trade and multiple profits
Racism and rights for Africans

redpajama_set_name: RedPajamaCommonCrawl


Check out my new updated Calendar of classes at Michael's in Las Vegas.
We have it jam packed full of classes on Paper Crafting of all sorts.
Check click above to see it. Click on the date for more of a description and some have photo attachments as well.


Co-owned by Newcastle Cycle Centre & holiday company Saddle Skedaddle the cafe/bike shop is smack bang on the C2C route.
The C2C cycle route is one of the UK's key challenge rides, attracting tens of thousands of riders each year. Those riding past Spillers Quay on Newcastle Quayside will now be able to grab a coffee while buying spares or having their bikes fixed. The Cycle Hub is due to open on 8th June.
The shop is in the former Quayside Regeneration Centre, a building owned by Newcastle City Council and which hasn't hadn't a fixed role for some years. While not vacant it hasn't been used to its full potential and this is why holiday company Saddle Skedaddle teamed up with Newcastle Cycle Centre to create The Cycle Hub.
This will have a cafe, cycle hire and bike shop. It will also be the base for Saddle Skedaddle, which runs trips on the C2C as well as cycle holidays around the world.


text:
Oldenburg in 2012
(1929-01-28)January 28, 1929
July 18, 2022(2022-07-18) (aged 93)
New York City, U.S.
American (from 1953)
Latin School of Chicago
Art Institute of Chicago
Notable work
List of public art by Oldenburg and van Bruggen
avant-garde[1]
Patty Mucha
(m. 1960; div. 1970)
Hannah Wilke (1969–1977)
Richard Oldenburg (brother)
Wolf Prize in Arts – Sculpture
Rolf Schock Prize – Visual arts
National Medal of Arts
Claes Oldenburg (January 28, 1929 – July 18, 2022) was a Swedish-born American sculptor, best known for his public art installations typically featuring large replicas of everyday objects. Another theme in his work is soft sculpture versions of everyday objects. Many of his works were made in collaboration with his wife, Coosje van Bruggen, who died in 2009; they had been married for 32 years. Oldenburg lived and worked in New York City.
Claes Oldenburg was born on January 28, 1929, in Stockholm, the son of Gösta Oldenburg[3] and his wife Sigrid Elisabeth née Lindforss.[4] His father was then a Swedish diplomat stationed in New York and in 1936 was appointed consul general of Sweden to Chicago where Oldenburg grew up, attending the Latin School of Chicago. He studied literature and art history at Yale University[5] from 1946 to 1950, then returned to Chicago where he took classes at The School of the Art Institute of Chicago. While further developing his craft, he worked as a reporter at the City News Bureau of Chicago. He also opened his own studio and, in 1953, became a naturalized citizen of the United States. In 1956, he moved to New York, and for a time worked in the library of the Cooper Union Museum for the Arts of Decoration, where he also took the opportunity to learn more, on his own, about the history of art.[6]
Main article: List of public art by Oldenburg and van Bruggen
Oldenburg's first recorded sales of artworks were[when?] at the 57th Street Art Fair in Chicago, where he sold 5 items for a total price of $25.[7] He moved back to New York City in 1956. There he met a number of artists, including Jim Dine, Red Grooms, and Allan Kaprow, whose happenings incorporated theatrical aspects and provided an alternative to the abstract expressionism that had come to dominate much of the art scene. Oldenburg began toying with the idea of soft sculpture in 1957, when he completed a free-hanging piece made from a woman's stocking stuffed with newspaper. (The piece was untitled when he made it but is now referred to as Sausage.)[8]
By 1960, Oldenburg had produced sculptures containing simply rendered figures, letters, and signs, inspired by the Lower East Side neighborhood where he lived, made out of materials such as cardboard, burlap, and newspapers; in 1961, he shifted his method, creating sculptures from chicken wire covered with plaster-soaked canvas and enamel paint, depicting everyday objects – articles of clothing and food items.[9] Oldenburg's first show which included three-dimensional works, in May 1959, was at the Judson Gallery, at Judson Memorial Church on Washington Square.[10] During this time, artist Robert Beauchamp described Oldenburg as "brilliant", due to the reaction that the pop artist brought to a "dull" abstract expressionist period.[11]
In the 1960s, Oldenburg became associated with the pop art movement and created many so-called happenings, which were performance art related productions of that time. The name he gave to his own productions was "Ray Gun Theater". The cast of colleagues who appeared in his performances included artists Lucas Samaras, Tom Wesselmann, Carolee Schneemann, Oyvind Fahlstrom and Richard Artschwager, art gallerist Annina Nosei, critic Barbara Rose, and screenwriter Rudy Wurlitzer.[8] His first wife (1960–1970) Patty Mucha[12] (Patricia Muchinski),[13] who sewed many of his early soft sculptures, was a constant performer in his happenings. His brash, often humorous, approach to art was at great odds with the prevailing sensibility that, by its nature, art dealt with "profound" expressions or ideas. But Oldenburg's spirited art found first a niche then a great popularity that endures to this day. In December 1961, he rented a store on Manhattan's Lower East Side to house "The Store", a month-long installation he had first presented at the Martha Jackson Gallery in New York, stocked with sculptures roughly in the form of consumer goods.[8]
Oldenburg moved to Los Angeles in 1963 "because it was the most opposite thing to New York [he] could think of".[8] That same year, he conceived AUT OBO DYS, performed in the parking lot of the American Institute of Aeronautics and Astronautics in December 1963. In 1965, he turned his attention to drawings and projects for imaginary outdoor monuments. Initially these monuments took the form of small collages such as a crayon image of a fat, fuzzy teddy bear looming over the grassy fields of New York's Central Park (1965)[14] and Lipsticks in Piccadilly Circus, London (1966).[15] In 1967, New York city cultural adviser Sam Green realized Oldenburg's first outdoor public monument; Placid Civic Monument took the form of a Conceptual performance/action behind the Metropolitan Museum of Art in New York City, with a crew of gravediggers digging a 6-by-3-foot rectangular hole in the ground.[5] In 1969, Oldenberg contributed a drawing to the Moon Museum. Geometric Mouse-Scale A, Black 1/6, also from 1969, was selected to be part of the Governor Nelson A. Rockefeller Empire State Plaza Art Collection in Albany, New York.[16]
Many of Oldenburg's large-scale sculptures of mundane objects elicited ridicule before being accepted. For example, the 1969 Lipstick (Ascending) on Caterpillar Tracks, was removed from its original place in Beinecke Plaza at Yale University, and "circulated on a loan basis to other campuses".[17] English art critic Ellen H. Johnson says that with its "bright color, contemporary form and material and its ignoble subject, it attacked the sterility and pretentiousness of the classicistic building behind it". The artist "pointed out it opposed levity to solemnity, color to colorlessness, metal to stone, simple to a sophisticated tradition. In theme, it is both phallic, life-engendering, and a bomb, the harbinger of death. Male in form, it is female in subject".[17] One of a number of Oldenburg's sculptures that possess interactive capabilities, it now resides in the Morse College courtyard.
From the early 1970s on, Oldenburg concentrated almost exclusively on public commissions.[15] His first public work, Three-Way Plug came on commission from Oberlin College with a grant from the National Endowment for the Arts.[18] His collaboration with Dutch/American writer and art historian Coosje van Bruggen dates from 1976. They were married in 1977. Oldenburg officially signed all the work he did from 1981 on with both his own name and van Bruggen's.[8] Their first collaboration came when Oldenburg was commissioned to rework Trowel I, a 1971 sculpture of an oversize garden tool, for the grounds of the Kröller-Müller Museum in Otterlo in the Netherlands.[19]
In 1988, the two created the iconic Spoonbridge and Cherry sculpture for the Walker Art Center in Minneapolis. It remains a staple of the Minneapolis Sculpture Garden as well as a classic image of the city. Typewriter Eraser, Scale X (1999) is in the National Gallery of Art Sculpture Garden. Another well known construction by the duo is the Free Stamp in downtown Cleveland.[20]
In addition to freestanding projects, they occasionally contributed to architectural projects, among them, two Los Angeles projects in collaboration with architect Frank Gehry: Toppling Ladder With Spilling Paint, which was installed at Loyola Law School in 1986, and the building-mounted sculpture Giant Binoculars,[21] completed in Venice Beach in 1991.[8] The couple's collaboration with Gehry also involved a return to performance for Oldenburg when the trio presented Il Corso del Coltello, in Venice, Italy, in 1985; other characters were portrayed by Germano Celant and Pontus Hultén.[22] "Coltello" is the source of Knife Ship, a large-scale sculpture that served as the central prop; it was later seen in Los Angeles in 1988 when Oldenburg, van Bruggen and Gehry presented Coltello Recalled: Reflections on a Performance at the Japanese American Cultural & Community Center and the exhibition Props, Costumes and Designs for the Performance "Il Corso del Coltello" at Margo Leavin Gallery.[8]
The city of Milan, Italy, commissioned the work known as Needle, Thread and Knot (Italian: Ago, filo e nodo) which was installed in 2000 in the Piazzale Cadorna.[23] In 2001, Oldenburg and van Bruggen created Dropped Cone, a huge inverted ice cream cone, on top of a shopping center in Cologne, Germany.[24] Installed at the Pennsylvania Academy of the Fine Arts in 2011, Paint Torch is a towering 53-foot-high (16 m) pop sculpture of a paintbrush, capped with bristles that are illuminated at night. The sculpture is installed at a daring 60-degree angle, as if in the act of painting.[25] In 2018, The Maze was included in 1968: Sparta Dreaming Athens at Château de Montsoreau-Museum of Contemporary Art.[26]
Artists Claes Oldenburg and Fay Peck with museum director Jan van der Marck in 1968
Oldenburg in Stedelijk Museum Amsterdam, 1970
Oldenburg's first one-man show, in 1959 at the Judson Gallery in New York, had shown figurative drawings and papier-mâché sculptures.[15] He was honored with a solo exhibition of his work at the Moderna Museet (organized by Pontus Hultén), in 1966; the Museum of Modern Art, New York, in 1969; London's Tate Gallery in 1970 (chronicled in a 1970 twin-projection documentary by James Scott called The Great Ice Cream Robbery[27]); and with a retrospective organized by Germano Celant at the Solomon R. Guggenheim Museum,[28] New York, in 1995 (travelling to the National Gallery of Art, Washington, D.C.; Museum of Contemporary Art, Los Angeles; Kunst- und Ausstellungshalle der Bundesrepublik Deutschland, Bonn; and Hayward Gallery, London). In 2002, the Whitney Museum of American Art in New York held a retrospective of the drawings of Oldenburg and van Bruggen; the same year, the Metropolitan Museum of Art in New York exhibited a selection of their sculptures on the roof of the museum.[5]
Oldenburg is represented by the Pace Gallery in New York[29] and Margo Leavin Gallery in Los Angeles.[30]
In 1989, Oldenburg won the Wolf Prize in Arts. In 2000, he was awarded the National Medal of Arts.[31] Oldenburg received honorary degrees from Oberlin College, Ohio, in 1970; Art Institute of Chicago, Illinois, in 1979; Bard College, New York, in 1995; and Royal College of Art, London, in 1996, as well as the following awards: Brandeis University Sculpture Award, 1971; Skowhegan Medal for Sculpture, 1972; Art Institute of Chicago, First Prize Sculpture Award, 72nd American Exhibition, 1976; Medal, American Institute of Architects, 1977; Wilhelm-Lehmbruck Prize for Sculpture, Duisburg, Germany, 1981; Brandeis University Creative Arts Award for Lifetime Artistic Achievement, The Jack I. and Lillian Poses Medal for Sculpture, 1993; Rolf Schock Foundation Prize, Stockholm, Sweden, 1995. He was a member of the American Academy and Institute of Arts and Letters from 1975 on and the American Academy of Arts and Sciences from 1978.[32]
Oldenburg and Coosje van Bruggen together received honorary degrees from the California College of the Arts, San Francisco, California, in 1996; University of Teesside, Middlesbrough, England, in 1999; Nova Scotia College of Art and Design, Halifax, Nova Scotia, in 2005; the College for Creative Studies in Detroit, Michigan, in 2005, and the Pennsylvania Academy of Fine Arts, 2011. Awards for their collaboration include the Distinction in Sculpture, SculptureCenter, New York (1994); Nathaniel S. Saltonstall Award, Institute of Contemporary Art, Boston (1996); Partners in Education Award, Solomon R. Guggenheim Museum, New York (2002); and Medal Award, School of the Museum of Fine Arts, Boston (2004).[32]
In her 16-minute, 16mm film Manhattan Mouse Museum (2011), artist Tacita Dean captured Oldenburg in his studio as he gently handles and dusts the small objects that line his bookshelves. The film is less about the artist's iconography than the embedded intellectual process which allowed him to transform everyday objects into remarkable sculptural forms.[33]
Patty Mucha, who was married to Claes Oldenburg from 1960 to 1970, first met him after moving to New York City in 1957 to become an artist. When Oldenburg was painting portraits, Mucha became one of his nude models[34] before becoming his first wife. An Oldenburg drawing of Mucha titled Pat Reading in Bed, Lenox, 1959[35] is in the collection of the Whitney Museum of American Art. She was a collaborator in Oldenburg's happenings by coming up with ideas together, making the costumes together, and was also a performer in the piece, along with collaborating on happenings, she also as well, sewed his famous floor hamburger, ice cream, and cake. Mucha was lead singer in the band The Druds who were a band of artists including Andy Warhol, LaMonte Young, Lucas Samaras, and Walter DeMaria pre-velvet underground.
Between 1969 and 1977, Oldenburg was in a relationship with the feminist artist and sculptor, Hannah Wilke, who died in 1993.[36] They shared several studios and traveled together, and Wilke often photographed him.
Oldenburg and his second wife, Coosje van Bruggen, met in 1970 when Oldenburg's first major retrospective traveled to the Stedelijk Museum in Amsterdam, where van Bruggen was a curator.[37] The couple were married in 1977.[38]
In 1992, Oldenburg and van Bruggen acquired Château de la Borde, a small Loire Valley chateau, whose music room gave them the idea of making a domestically sized collection.[37] Van Bruggen and Oldenburg renovated the house, decorating it with modernist pieces by among others Le Corbusier, Charles and Ray Eames, and Alvar Aalto, Frank Gehry, Eileen Gray.[39] Van Bruggen died on January 10, 2009, from the effects of breast cancer.[19]
Oldenburg's brother, art historian Richard E. Oldenburg, was director of the Museum of Modern Art, New York, between 1972 and 1993,[8] and later chairman of Sotheby's America.[40]
On July 18, 2022, Oldenburg died at his home in Manhattan from complications of a fall, aged 93.[41]
Oldenburg's sculpture Typewriter Eraser (1976), the third piece from an edition of three, was sold for $2.2 million at Christie's New York in 2009.[42]
Flying Pins by Claes Oldenburg and Coosje van Bruggen, Eindhoven, Netherlands
Giant Pool Balls (1977) by Claes Oldenburg and Coosje van Bruggen for Skulptur Projekte Münster, Münster, Germany
The Garden Hose, Freiburg im Breisgau, Baden-Württemberg, Germany
Screw Arch, Museum Boijmans Van Beuningen, Rotterdam, Netherlands
Shuttlecocks by Claes Oldenburg and Coosje van Bruggen, Nelson-Atkins Museum of Art, Kansas City, Missouri
Spring 2006, Coosje van Bruggen and Claes Oldenburg, Cheonggyecheon, Seoul, South Korea
Bottle O' Notes, Middlesbrough, North Yorkshire, England
Dropped Cone 2001, Claes Oldenburg and Coosje van Bruggen, Neumarkt area, Cologne, Germany
Giant Binoculars, Chiat/Day Building, Venice, Los Angeles, California
May 1974, Clothespin is a weathering steel sculpture by Claes Oldenburg, located at Centre Square, 1500 Market Street, Philadelphia
Cupid's Span, San Francisco
General and cited references
Axsom, Richard H., Printed Stuff: Prints, Poster, and Ephemera by Claes Oldenburg A Catalogue Raisonne 1958–1996 (Hudson Hills Press: 1997) ISBN 1-55595-123-6
Busch, Julia M., A Decade of Sculpture: the New Media in the 1960s (The Art Alliance Press: Philadelphia; Associated University Presses: London, 1974) ISBN 0-87982-007-1
Gianelli, Ida and Beccaria, Marcella (editors) Claes Oldenburg Coosje van Bruggen: Sculpture by the Way Fundació Joan Miró 2007
Haskell, Barbara. Claes Oldenburg, Pasadena, CA: Pasadena Art Museum, 1971
Höchdorfer, Achim, Claes Oldenburg: The Sixties (Prestel: USA, 2012) ISBN 3-7913-5205-9
Johnson, Ellen H. Claes Oldenburg, Penguin Books, (Harmondsworth, Middlesex, England; Baltimore, Maryland, USA; Ringwood, Victoria, Australia), 1971
Oldenburg, Claes. Log May 1974 – August 1976, Stuttgart: edition hansjorg mayer, 1976 (Two volume boxed set: "Photo Log" and "Press Log")
Oldenburg, Claes. Raw Notes: Documents and Scripts of the Performances: Stars, Moveyhouse, Massage, The Typewriter, with annotations by the author. (The Press of the Nova Scotia College of Art and Design: Halifax, 2005) ISBN 0-919616-43-7
Thalacker, Donald W. "The Place of Art in the World of Architecture." Chelsea House Publishers, New York, 1980. ISBN 0-87754-098-5
Valentin, Eric, Claes Oldenburg, Coosje van Bruggen. Le grotesque contre le sacré, Paris, collection Art et artistes, Gallimard, 2009. ISBN 978-2-07-078627-5
Valentin, Eric, Claes Oldenburg et Coosje van Bruggen. La sculpture comme subversion de l'architecture (1981–1997), Dijon, collection Inflexion, Les Presses du réel [fr], 2012 ISBN 978-2-84066-450-5
^ James O. Young (2001). Art and Knowledge. New York: Routledge, p. 135.
^ a b "Claes Oldenburg obituary". The Guardian. July 18, 2022. Retrieved July 19, 2022. Oldenburg was married to Patty Mucha (nee Muchinski) from 1960 until their divorce in 1970, and to Coosje van Bruggen from 1977 until her death. His brother Richard died in 2018. He is survived by his stepdaughter, Maartje, and stepson, Paulus.
^ "Gosta Oldenburg; Retired Diplomat, 98". The New York Times. April 1, 1992. Retrieved April 29, 2014.
^ "Biografía y obras: Oldenburg, Claes". Guggenheim Bilbao. May 10, 2012. Retrieved July 18, 2022.
^ a b c Claes Oldenburg Archived May 10, 2012, at the Wayback Machine Guggenheim Collection.
^ "Claes Oldenburg." Encyclopedia of World Biography. Chicago: Fitzroy Dearborn, 1998; later: Gale. Retrieved via Biography in Context database, October 22, 2017.
^ David McCracken, "The Art Fair That's Been In the Picture the Longest", Chicago Tribune, June 5, 1987, page 3
^ a b c d e f g h Kristine McKenna (July 2, 1995), When Bigger Is Better: Claes Oldenburg has spent the past 35 years blowing up and redefining everyday objects, all in the name of getting art off its pedestal Los Angeles Times.
^ "Claes Oldenburg: On View, Apr 14 – Aug 5, 2013". Museum of Modern Art. moma.org. Sections "Introduction", The Street" and "The Store". Retrieved October 23, 2017.
^ Claes Oldenburg, "Remembering Judson House," New York: Judson Memorial Church, p. 292
^ Paul Cummings (1975). "Oral history interview with Robert Beauchamp, 1975 Jan. 16". Oral history interview. Archives of American Art. Retrieved June 30, 2011.
^ "Six Feet of the 1960s and '70s: Patty Mucha—Once Mrs. Oldenburg—on Her Archives and New Memoir". The New York Observer. January 16, 2012.
^ "Guide to the The[sic] Patty Mucha Papers, 1949 – 2016 MSS.342". dlib.nyu.edu.
^ Christopher Knight (August 6, 1995), The Percolating Mind of Oldenburg : A retrospective shows how ideas from early in a career can cook for decades, before emerging to enshrine the mundane Los Angeles Times.
^ a b c Claes Oldenburg Museum of Modern Art, New York.
^ "Explore The Art Collection". Visit the Empire State Plaza & New York State Capitol.
^ a b Johnson, Ellen H. (1971). Claes Oldenburg. Harmondsworth, Middlesex, England: Penguin Books. p. 46.
^ Duffes, Melissa. "Oldenburg's First Commissioned Public Sculpture Returns to AMAM". Oberlin College. Retrieved October 12, 2013.
^ a b Carol Kino (January 13, 2009), Coosje van Bruggen, Sculptor, Dies at 66 The New York Times.
^ Roy, Chris; Edmonds, Joe. "The Free Stamp". Cleveland Historical. Retrieved August 10, 2020.
^ "PUBLIC ART IN PUBLIC PLACES – "Giant Binoculars" (1991) by Claes Oldenburg, Coosje van Bruggen". publicartinpublicplaces.info. Retrieved July 19, 2022.
^ Claes Oldenburg: Props, Costumes and Designs for the Performance "Il Corso del Coltello", January 9 – February 13, 1988 Margo Leavin Gallery, Los Angeles.
^ "Needle, Thread and Knot in Piazzale Cadorna". in-Lombardia: The Official Tourism Information Site for Lombardy. June 14, 2021. Retrieved July 19, 2022.
^ "Dropped Cone". Oldenburgvanbruggen.com. Retrieved April 29, 2014.
^ "Oldenburg's Paint Torch | 1805". Pafa.org. Retrieved April 29, 2014.
^ Sevior, Michelle (November 7, 2018). "ArtPremium – 1968 – Sparta Dreaming Athens at Château de Montsoreau-Museum Contemporary Art". ArtPremium. Retrieved August 10, 2019.
^ "Double vision: the joys of twin-projection cinema". British Film Institute. Retrieved December 1, 2015.
^ John Russell (March 6, 1995), Oldenburg Again: Whimsy and Latent Humanity The New York Times.
^ "Remembering Claes Oldenburg". Pace Gallery. December 18, 2021. Retrieved July 19, 2022.
^ "Margo Leavin Gallery – Institution". ArtFacts. Retrieved July 19, 2022.
^ Lifetime Honors – National Medal of Arts Archived March 4, 2010, at the Wayback Machine
^ a b Oldenburg Biography Pennsylvania Academy of the Fine Arts, Philadelphia.
^ Tacita Dean: Five Americans, May 6 – July 1, 2012, Archived April 15, 2013, at archive.today New Museum of Contemporary Art, New York.
^ "Patty [Oldenberg] Mucha Archive | Granary Books". granarybooks.com. Archived from the original on May 10, 2020. Retrieved July 19, 2020.
^ "Claes Oldenburg | Pat Reading in Bed, Lenox". whitney.org. Retrieved July 19, 2020.
^ Nancy Princenthal, Hannah Wilke, Prestel Publishing, New York
^ a b Carol Kino (May 15, 2009), Going Softly Into a Parallel Universe The New York Times.
^ "Claes Oldenburg & Coosje van Bruggen: Biographies". OldenburgVanBruggen.com. Retrieved April 13, 2011.
^ Michael Peppiatt (April 2005), The Art of Inspiration – Claes Oldenburg and Coosje van Bruggen Engage the Unexpected in the Loire Valley Architectural Digest.
^ Carol Vogel (March 17, 1995), Modern's Ex-Chief Joins Sotheby's The New York Times.
^ Bernstein, Fred (July 18, 2022). "Claes Oldenburg, a whimsical father of pop art, dies at 93". The Washington Post. Retrieved July 18, 2022.
^ Claes Oldenburg, Typewriter Eraser (1976) Christie's Post War with the Contemporary Evening Sale, April 20, 1969.
Wikimedia Commons has media related to Claes Oldenburg.
Claes Oldenburg and Coosje van Bruggen's website
The Pace Gallery
Claes Oldenburg at the Museum of Modern Art
Portraits of Claes Oldenburg at the National Portrait Gallery, London
Oldenburg page at the Guggenheim Museum site
An anthology of Oldenburg's work, includes brief bio
National Gallery of Art Claes Oldenburg: Making the Ordinary Extraordinary
Pop Art Masters – Claes Oldenburg
Biography of Claes Oldenburg
Claes Oldenburg in the National Gallery of Australia's Kenneth Tyler collection
An editorial of Oldenburg's work, highlighting five of his large-scale public sculptures
Claes Oldenburg and Coosje van Bruggen
Sculptures by Oldenburg
Lipstick (Ascending) on Caterpillar Tracks (1969)
Geometric Mouse, Variation I, Scale A (1971)
Clothespin (1976)
Sculptures by Oldenburg and van Bruggen
Batcolumn (1977)
Spoonbridge and Cherry (1988)
Inverted Collar and Tie (1994)
Typewriter Eraser, Scale X (1999)
Needle, Thread and Knot (2000)
Cupid's Span (2002)
Free Stamp (1991)
Binoculars Building (1991)
Awards for Claes Oldenburg
Laureates of the Wolf Prize in Arts
Ralph Erskine (1983/4)
Fumihiko Maki / Giancarlo De Carlo (1988)
Frank Gehry / Jørn Utzon / Denys Lasdun (1992)
Frei Otto / Aldo van Eyck (1996/7)
David Chipperfield / Peter Eisenman (2010)
Phyllis Lambert (2016)
Moshe Safdie (2019)
Elizabeth Diller / Momoyo Kaijima / Yoshiharu Tsukamoto (2022)
Vladimir Horowitz / Olivier Messiaen / Josef Tal (1982)
Isaac Stern / Krzysztof Penderecki (1987)
Yehudi Menuhin / Luciano Berio (1991)
Zubin Mehta / György Ligeti (1995/6)
Pierre Boulez / Riccardo Muti (2000)
Mstislav Rostropovich / Daniel Barenboim (2004)
Giya Kancheli / Claudio Abbado (2008)
Plácido Domingo / Simon Rattle (2012)
Jessye Norman / Murray Perahia (2015)
Paul McCartney / Ádám Fischer (2018)
Marc Chagall / Antoni Tàpies (1981)
Jasper Johns (1986)
Anselm Kiefer (1990)
Gerhard Richter (1994/5)
Louise Bourgeois (2002/3)
Michelangelo Pistoletto (2006/7)
Rosemarie Trockel (2011)
Cindy Sherman (2020)
Eduardo Chillida (1984/5)
Claes Oldenburg (1989)
Bruce Nauman (1993)
James Turrell (1998)
Olafur Eliasson (2014)
Laurie Anderson / Lawrence Weiner (2017)
Rolf Schock Prize laureates
Logic and philosophy
Willard Van Orman Quine (1993)
Michael Dummett (1995)
Dana Scott (1997)
John Rawls (1999)
Saul Kripke (2001)
Solomon Feferman (2003)
Jaakko Hintikka (2005)
Thomas Nagel (2008)
Hilary Putnam (2011)
Derek Parfit (2014)
Ruth Millikan (2017)
Saharon Shelah (2018)
Dag Prawitz / Per Martin-Löf (2020)
David Kaplan (2022)
Elias M. Stein (1993)
Andrew Wiles (1995)
Mikio Sato (1997)
Yuri I. Manin (1999)
Elliott H. Lieb (2001)
Richard P. Stanley (2003)
Luis Caffarelli (2005)
Endre Szemerédi (2008)
Michael Aschbacher (2011)
Yitang Zhang (2014)
Richard Schoen (2017)
Ronald Coifman (2018)
Nikolai G. Makarov (2020)
Jonathan Pila (2022)
Torsten Andersson (1997)
Giuseppe Penone (2001)
Susan Rothenberg (2003)
SANAA / Kazuyo Sejima + Ryue Nishizawa (2005)
Mona Hatoum (2008)
Marlene Dumas (2011)
Anne Lacaton / Jean-Philippe Vassal (2014)
Doris Salcedo (2017)
Andrea Branzi (2018)
Francis Alÿs (2020)
Ingvar Lidholm (1993)
György Ligeti (1995)
Jorma Panula (1997)
Kronos Quartet (1999)
Kaija Saariaho (2001)
Anne Sofie von Otter (2003)
Mauricio Kagel (2005)
Gidon Kremer (2008)
Andrew Manze (2011)
Herbert Blomstedt (2014)
Wayne Shorter (2017)
Barbara Hannigan (2018)
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Víkingur Ólafsson (2022)
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National Public Radio, cultural programming division
Alvin Ailey Dance Foundation
Mike Nichols
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ODAC to Review AVEO Oncology's Investigational Drug Tivozanib in the Treatment of Renal Cell Carcinoma
April 29, 2013 - 10:04 am Posted in Featured 0 Comments
In February 2013, AVEO Oncology and Astellas Pharma Inc. announced results from their controlled, multi-center, open-label, TIVO-1 study that compared the investigational VEGF inhibitor, tivozanib, head-to-head with the VEGF inhibitor, sorafenib [Nexavar; BayerHealthcare, Onyx Pharmaceuticals] in recurring or metastatic renal cell carcinoma. Patients (N=517) were randomized to tivozanib or sorafenib and must have undergone prior nephrectomy (complete or partial) for excision of the primary tumor.
On May 2, 2013, the FDA's Oncologic Drug Advisory Committee (ODAC) is meeting to discuss the efficacy and safety of tivozanib and will decide its fate. Seemingly, this is business as usual until a review of the dynamics in play makes ODAC's yea or nay vote on tivozanib an interesting one to follow.
In the final analysis of TIVO-1, tivozanib demonstrated a statistically significant improvement in progression-free survival (PFS), the primary endpoint of the study, when compared with sorafenib: median PFS 11.9 months in the tivozanib arm vs 9.1 months for sorafenib. However, in the secondary endpoint that measured overall survival (OS), results showed that there was no statistical difference between the two arms. The final OS analysis shows a median OS of 28.8 months for tivozanib versus a median OS of 29.3 months for the sorafenib arm.
At first look, given the OS results, it would seem as if tivozanib did not perform any better (or worse) than its comparator; yet what is confounding the OS results is the fact that the TIVO-1 trial design allowed patients in the sorafenib arm to switch over to the tivozanib arm once their disease progressed. Roughly 74% of patients in the sorafenib arm received a subsequent therapy in the trial versus 36% in the tivozanib arm.
How ODAC will respond to a drug whose OS fared about the same as its comparator, but showed superiority in PFS brings the question of PFS vs OS as a gold standard under scrutiny once again. The validity of PFS and OS as endpoints has been debated before. Furthermore, crossover of patients in cancer clinical trials is a recognized phenomenon, confounding results, and casting shadows of doubt on trial endpoints.
In The Street, Adam Feuerstein is predicting a negative vote by the ODAC panel for recommendation to the FDA. He states, "Admittedly, my conviction level for this prediction isn't all that strong. Today's FDA seems addicted to approving all drugs, so the agency may be unwilling to subject tivozanib to the scrutiny it deserves. If the FDA takes it easy on tivozanib, the advisory panel may do the same."
He is basing his prediction on the analysis of the OS data over a 2-year period in which the relative risk of death was 25% higher in the tivozanib arm vs the control arm. The greater risk of death between the 2 groups was not statistically significant. "That might work in Aveo's favor, but a hazard ratio of 1.245 against tivozanib is alarming — even if not statistically significant — and raises serious questions about the drug or the conduct of the study," he states.
To read more click here: http://www.thestreet.com/story/11905026/1/why-aveos-kidney-cancer-drug-will-be-turned-down-by-next-weeks-fda-panel.html
Supporting the tivozanib recommendation by the ODAC committee is Aafia Chaudhry, MD. In an online article in PropThink, Dr. Chaudhry writes, "we see very little to suggest that a panel would vote against approval of this drug. While some may argue that the RCC market is crowded, we see tivozanib being used as an alternative to other oral therapies in the frontline setting. The agent's beneficial dosing cycle and superior tolerability profile make this an exciting addition to the current armamentarium. We believe oncologists would want to have this available in the clinic to offer patients. It also adds a useful alternative to more toxic agents used in sequencing for subsequent lines of therapy."
To read more click here: http://propthink.com/aveos-inflection-point-tivozanib-likely-to-receive-positive-advisory-vote-fda-approval/5898
Kimryn Rathmell, MD, PhD, Associate professor, The University of North Carolina, Chapel Hill, is a translational scientist and a medical oncologist dedicated to the care of patients with kidney cancer. According to Dr. Rathmell, "Going before ODAC, we have no clear OS advantage with tivozanib as compared with sorafinib, yet PFS is positively impacted at 8.4 months in the investigational arm."
In patients who were treatment naïve (70% of total study population), tivozanib demonstrated a statistically significant improvement in PFS with a median of 12.7 months vs 9.1 months for sorafenib. According to the AVEO Oncology press release, "This is the longest median PFS reported to date in treatment-naïve advanced RCC patients in a pivotal study."
In addition to meeting its endpoints, tivozanib demonstrated a good safety profile, with patients tolerating the drug well. The most common adverse event reported was hypertension which is consistent with the safety profile of the Phase 2 study. When asked about the possibility of ODAC not recommending the drug for FDA approval, Rathmell said, "This is a drug that has a strong PFS and a good side effect profile. It would be disappointing to go back to a Phase 3 trial because of a crossover."
In the United States, kidney cancer is expected to occur in over 65,000 people in 2013, with over 13,000 deaths being attributed to the disease. The death rate is fairly steady annually, and most people don't know they have it until it is in its advanced stage. "It's a sneaky disease," says Rathmell, "about one-third of tumors will reoccur after patients undergo resection."
To treat the disease, the mainstay of available therapies is tyrosine kinase inhibitors (TKIs) that target the VEGF receptor. "Chemo doesn't really work," says Rathmell, "because the disease is very vascular. TKI drugs, [such as tivozanib and sorafanib], target the vasculature; not really the cancer cells."
Targeting the VEGF receptor is just one corner of the market. "Standard of care used to be interferon even though it was never FDA approved," says Rathwell. "It's toxic, hard to give, and only works for a very small margin of patients. With the TKIs most people can take them and get some kind of response."
In the TKI era, Rathmell assures, the survival time per patient is increasing. "Patients are living longer by a good margin than they were in the interferon era; and collectively, this can't be pointed to just one drug in the renal cell armamentarium of drugs targeting cancers."
Every drug opens up a new therapy choice for some patients. If approved, tivozanib will provide another option for patients with RCC as there's always a patient that can match up better with a new drug than an already existing drug. "The goal is to achieve a long term of disease control without completely destroying quality of life," says Rathmell.
Is PFS a clinically meaningful endpoint in cancer clinical trials, especially when crossover is part of the study design? Stay tuned – it will probably be a nail biter. First we'll see the FDA's review of the file and then we have ODAC on May 2nd.
By John McCleery, Managing Editor, OBR
Mining the Pipeline: Addressing Unmet Needs in Oncology
April 19, 2013 - 04:04 pm Posted in Featured 0 Comments
New entrants into the oncology marketplace can distinguish themselves in a number of ways. One approach is to be first-in-class with a novel mechanism of action (MOA) – this is true for over one-half of the pipeline agents in pivotal development. Another development strategy is to target an indication with high unmet need, offering a valuable new treatment approach for patients with few options. Of course, all cancer indications have rather high unmet need compared with non-oncology indications due to the life-threatening nature of the disease; however, among the numerous cancer indications, the level of need may vary considerably. Among 69 pipeline agents that are in pivotal clinical development in oncology, only one-third of ongoing pivotal studies with pipeline agents are being conducted in indications with relatively high unmet need1 (Figure 1). These indications include relapsed refractory acute leukemias; second-line therapy for gastric cancer, pancreatic cancer and hepatocellular carcinoma; and fourth-line therapy for multiple myeloma and renal cell carcinoma.
Areas of unmet need may be growing as clinical research continues to identify new biomarkers that identify mechanisms that drive a particular patient's tumor or that confer a worse prognosis. Patients in these categories may have treatment options in the available armamentarium, but those options may be less effective than a targeted agent directed at their tumor's specific molecular profile, making this a new area of unmet need. However, despite the oncology community's growing focus on personalized medicine, only 22% of pipeline agents currently in pivotal trials are being developed in a biomarker-defined patient population. Novel biomarker populations that are currently being studied in pivotal trials in oncology are summarized in Table 1. Many more are being evaluated in early-stage exploratory studies and could begin to affect the market in the next five years.
Through extensive analysis based on a combination of product and indication attributes,2 Kantar Health has evaluated and rated these 69 pipeline agents to identify those with the greatest likelihood of clinical impact in the next three years. Five pipeline agents have emerged as having significant "breakthrough" potential, based primarily on the merits of their clinical data and independent of target indication attributes. We believe these five agents have the potential to dramatically improve efficacy outcomes and may transform the standard of care in their target indications.
1.	Dabrafenib + Trametinib
GlaxoSmithKline is developing the BRAF inhibitor dabrafenib and the MEK inhibitor trametinib in melanoma patients with the BRAF-mutation. As monotherapies, neither dabrafenib nor trametinib raises eyebrows. In combination, however, they may be a force to be reckoned with. In a randomized Phase II trial, the combination significantly prolonged progression-free survival (PFS) compared with dabrafenib alone while also reducing the incidence of key toxicities associated with this class of agents. These data are currently being explored in Phase III trials, but Kantar Health anticipates the National Comprehensive Cancer Network (NCCN) will recommend use of the combination regimen based on the highly positive randomized Phase II data, giving this combination a near-term impact on the melanoma market (approval of each agent as a monotherapy is expected in 2013).
2.	Ibrutinib
The Bruton's tyrosine kinase (Btk) pathway is a downstream mediator of the B-cell receptor pathway, making ibrutinib a novel mechanistic approach to the treatment of B-cell malignancies. Ibrutinib has demonstrated robust activity in heavily pretreated chronic lymphocytic leukemia (CLL) and mantle cell lymphoma (MCL). Furthermore, ibrutinib is amazingly well-tolerated, with very few serious adverse events. The lack of significant toxicity opens the door for it to be combined with current standards of care. Capitalizing on the early efficacy signals, Pharmacyclics and Johnson & Johnson are pursuing multiple pivotal trials of ibrutinib in relapsed/refractory CLL and MCL.
3.	Idelalisib
The PI3K pathway undoubtedly represents one of the hottest drug targets in oncology. Idelalisib is the most advanced of the isoform-specific PI3K inhibitors, and it made a big splash when it produced high response rates and PFS in heavily pretreated CLL and non-Hodgkin's lymphoma (NHL) patients in early trials. Although it's not without toxicity, the observed toxicities don't overlap with those associated with current standards of care in CLL and NHL, leaving open the possibility for idelalisib to be combined with existing regimens. Following its 2011 acquisition of Calistoga, Gilead has charged ahead with the development of idelalisib, initiating four Phase III trials in relapsed/refractory CLL and indolent NHL.
4.	Nivolumab
Nivolumab (anti-PD-1 monoclonal antibody, BMS) demonstrated impressive activity in a large, first-in-man Phase I trial, with durable objective responses observed in several solid tumors. On top of these efficacy outcomes, nivolumab impressed with its rather tolerable safety profile. From this single (albeit large) trial, Bristol-Myers Squibb plowed ahead, initiating five Phase III trials in three tumor types (melanoma, NSCLC and renal cell carcinoma). The strong Phase I data, good safety profile, broad applicability across multiple tumors and the possibility for a predictive biomarker all contribute to nivolumab's potential breakthrough status.
5.	Palbociclib (PD-0332991)
PD-0332991 (palbociclib; Pfizer) wowed the audience at the 2012 San Antonio Breast Cancer Symposium (SABCS) annual meeting with an 18+-month improvement in median PFS in a randomized Phase II trial of letrozole with or without PD-0332991 as first-line therapy for ER+ metastatic breast cancer. As a CDK 4/6 inhibitor, it will be first-in-class if it hits the market, although inhibitors of other CDKs are also in late-stage development. Although currently in pivotal development only for metastatic breast cancer, the eventual development of this agent in earlier-stage breast cancer can be foreseen, and Pfizer is also investigating the drug in a number of other solid tumors. With broad applicability and stunning Phase II data, PD-0332991 has the ability to be a breakthrough agent in the treatment of cancer.
These five agents are just the tip of the iceberg. The oncology pipeline continues to grow, and the number of novel MOAs in development offer significant promise toward improving outcomes in a variety of indications. The past couple of years have seen some significant breakthroughs in cancer management, and the next few years have great potential to similarly transform care and outcomes.
1.	The level of unmet needs was calculated based on the number of existing treatment options in the target indication (with fewer treatment options correlating with higher need), the rate of treatment (with high non-treatment rates correlating with higher need), and efficacy outcomes achieved with current options (with short survival times correlating with higher need). High overall scores for the sum of these three attributes were considered to be a high unmet need, whereas low overall scores were considered to be a low unmet need.
2.	Attributes that were scored included mechanistic innovation, strength of prior published data, target indication population size, and level of competition. For more in-depth information on Kantar Health's scoring methodology, please e-mail info@kantarhealth.com.
By: Stephanie Hawthorne, PhD, Director, Kantar Health
AACR 2013 Post-View: Getting Closer To Bending The Curve For More Patients
After AACR 2012 in a piece we called "A Science Geek's Thoughts on the 2012 AACR Annual Scientific Meeting", we wrote about three larger-picture, emerging themes that we felt worth discussing: epigenetics, tumor cell metabolism, and cancer stem cell biology (science that leads to the exploitation of the stem cell for novel drug targets for therapeutic interdiction, not stem cells themselves as therapies). While these themes certainly repeated themselves in 2013, epigenetics and cancer stem cell research have matured, while tumor cell metabolism seems to still be searching for its killer app (although we continue to hear that Agios is very close to putting a molecule into the clinic after having recently published data on two inhibitors of IDH1 and IDH2 in the April 4 edition of Science). We also would add another concept that has caught our eye in the past, and that is the promise of harnessing the body's immune system to fight cancer and produce long-lasting benefit. While this concept is hardly new as Bristol-Myers' (BMY, NC) Yervoy (ipilimumab,) has been approved since May of 2011; however, Yervoy has not been, per se, a biotech pure-play. Further, the drug's tolerability issues will likely limit its uptake and duration of use. This year, Bristol's nivolumab has reset the bar for long-term benefit along with tolerability, even though its first-in-human study was published in the Journal of Clinical Oncology in 2010; likewise, nivolumab was the subject of two articles in the New England Journal of Medicine in 2012. We believe that future hindsight will mark the AACR 2013 plenary session as a harbinger for future ASCO plenary sessions. Inspiring talks were offered by Katie Couric regarding her crusade against colorectal cancer and role in creating Stand Up to Cancer (SU2C) as well as Siddhartha Mukherjee of Columbia University and author of The Emperor of All Maladies (a must-read, in our view). On a personal note, the AACR program organizers are to be commended for putting together a plenary agenda that was decidedly a non-snoozer.
Immunotherapy: When the Body Cures the Body
The common theme amongst the various presentations at the AACR plenary (as well as others throughout the conference) concerned complete eradication of tumors and/or durable remission of effect. Perhaps most emblematic of this was the talk given by Suzanne Topalian of The Kimmel Cancer Center at Johns Hopkins University. Dr. Topalian, the lead author of the 2012 NEJM article, discussed the biology of the PD-1/PD-L1 axis and the differences between it and the CTLA-4 axis, the target of Yervoy. Nivolumab blocks the binding of both PD-L1 and PD-L2 to the PD-1 receptor. She then discussed findings of both the JCO and NEJM articles, which examined the use of nivolumab in non-small cell lung cancer (NSCLC), melanoma, kidney, colon or prostate cancer. What most impressed us, and immediately caused us to crystallize the impact on patients of Dr. Topalian's data, was the slide she showed on the durability of response of three patients who has ceased treatment with nivolumab. Dr. Topalian provided vignettes of three patients-one with colorectal cancer (CRC), one with renal (kidney) cancer (RCC), and one with melanoma-showing that patients can remain in complete or partial response 4-5 years into their therapy. The patient with CRC remains in complete response just short of four years into follow up after stopping treatment shy of one year. The RCC patient received therapy for approximately six months had a partial response (PR) as best response shortly thereafter, then went on to produce a complete response (CR) at roughly 3.5 years, and at nearly 4.5 years remains in CR. Finally, Dr. Topalian's example of the melanoma patient was a bit more complicated. The patient achieved a PR just shy of two years on therapy, was diagnosed with a new metastasis just over three years after diagnosis, was retreated to a PR at year four, and was still in PR at roughly 4.5 years. Dr. Topalian also showed a slide that she showed at ESMO 2012. The key data point on this slide is a bullet that indicated 28 of 54 responses lasted more than one year in patients who had more than one year of follow-up. Grade 3-4 adverse events were a very reasonable 15%, and treatment-related mortality was only 1%. Perhaps most exciting was the slide shown by Dr. Topalian that described a patient with squamous non-small cell lung cancer, a tumor type that is widely thought to be non-immunogenic. This particular patient responded to anti-PD-1 antibody therapy after an immediately previous treatment with epigenetic therapy of 5-azacitidine (Vidaza, CELG, MO) and entinostat (Syndax, private, NC), an inhibitor of HDAC 6. Dr. Topalian indicated that this patient has recently completed two years of anti-PD-1 therapy. Moreover, Dr. Topalian indicated that there are five more patients like the one in the example she cited who have achieved durable responses after prior treatment with epigenetic therapy. While the number of patients is small, the 100% response rate in this population is impressive. We eagerly await the presentation of these data at an upcoming scientific conference. In terms of biomarkers and other correlates of response, Dr. Topalian showed a number of slides that spoke to the level of PD-L1 in the tissue as the most highly predictive of response in patients. In her findings, 13/31 patients with detectable levels (>5% of tumor cells) of PD-L1 achieved a PR or CR, whereas 0/18 patients with undetectable levels of PD-L1 did so. This has intuitive appeal to us, as it likely means that those patients without detectable PD-L1 have some other immune mediator of their disease. She also showed that patients whose disease had evidence of tumor infiltrating lymphocytes (TILs) experience improvements in overall survival. Dr. Topalian closed with suggestions as to how best to improve the therapeutic profile of these remarkable antibodies. These involved the blockade of lymphocyte activation gene 3, or LAG-3, and the blockade of interleukin-10 (IL-10), a cytokine known to tamp down the immune response to cancer cells, among other functions. We look forward to future developments with not only anti-PD-1 and PDL-1 therapy, as well as others that will enhance their effects.
Apart from the very cool science that was on display during Dr. Topalian's talk, we were struck by the thought of the effect on patients as the knowledge of the durable effect of PD-1 blockade make its way across patient blogs and discussion groups. What patient would not want to be cancer-free for three, four, five years or more? Anti-PD-1 therapy could make this possible. Even if the duration of response diminishes over time, as it inevitably will, we believe the pull of durable response could eventually make drugs in the class the largest selling oncology drugs extant. The robust effect, broad applicability, and acceptable tolerability could result in sales of the drugs that would put sales of Avastin (~$6 billion) to shame. Were Vidaza, Dacogen, or SGI-110 to hitch their respective wagons to the PD-1 bandwagon, it would likely be an unmitigated (and currently unanticipated) boon to the top line for these drugs. We take a deeper dive into the science later in this report.
Engaging Scientists in a Discussion about Stem Cells with Slick Graphics
The JMP Securities Award for the Sexiest Scientific Graphics goes to Hans (a/k/a "Very") Clevers of the Hubrecht Institute in Utrecht, The Netherlands. Dr. Clevers talk was peppered with some of the slickest scientific animations and graphics we have ever seen this side of the SciFi Channel. If every science teacher in America had access to graphics like this we would end the crisis in science education virtually overnight. Sadly, we speculate that Dr. Clevers presentation must have been hideously expensive and that he is the fortunate recipient of gobs of grant money. Having said that, Dr. Clevers scientific findings were as informative as his graphics were elegant. His work focuses on Lgr5 cells in the intestinal crypt, where stem cells demonstrate significant proliferation; a gut stem cell can transform itself into an enterocyte or goblet cell in the space of roughly five days then die within days, a huge turnover rate compared to other cells in the body. Most of Dr. Clevers' talk concerned his work on the creation of a gut model he and his research team derived from Lgr5 cells, which they can use in vitro and in vivo; however, we were encouraged by his further validation of some of our favorite cancer stem cell targets, including wnt, frizzled, LRP, Lgr and Rspo. All of these components comprise a sophisticated signaling complex on the exterior of the cells of the colon. In colorectal cancer, the wnt signaling pathway is locked in the "on" position, while Rspo binding to Lgr activates Lgr and, in turn, Lgr then binds to LRP and amplifies wnt-mediated signaling. The Lgr5 cells can be readily located as they are in contact with so-call Paneth cells, which also are found in the intestinal crypt, and appear to nurture the Lgr5 cells. In Dr. Clevers' words, every cell that touches a Paneth cell is a stem cell, and Paneth cells secrete gobs of wnt3 as part of their support role to the Lgr5 cell. Dr. Clevers also showed that inhibition of the protein porcupine, can block the secretion of wnt. Novartis (NVS, NC) is developing a small molecule inhibitor of porcupine, referred to as LGK974. In addition, privately-held OncoMed Pharmaceuticals is developing OMP-54F28, an antagonist of the wnt signaling pathway.
Session on Epigenetics Packs the House
The Sunday morning plenary session on epigenetics, hosted by Robert Copeland, PhD, Chief Scientific Officer of privately-held Epizyme, played to a packed house. While there were multiple sessions held during the five days of AACR on epigenetics, none was as forward-looking nor as absolutely packed as this one (an estimate of the number of attendees to the session exceeded 10,000). Peter Laird of the USC Epigenome Center in Los Angeles led the speaker's roster and provided a fascinating discussion of how the epigenetic signature of cancer cells is vastly different than that of normal cells in terms of both the number of genes silenced as well as turned on (or "de-silenced"). Dr. Laird showed that there is massive ("focal") hypermethylation at CpG islands (the start sites for gene transcription) across a wide variety of tumor types. These regions of hypermethylation are in areas of gene expression that would normally be associated with genes that would either prevent the outbreak of cancer or provide signals to the cancer cell that would normally tell cancer cells to die. What was particularly fascinating about Dr. Laird's talk was not only did he provide us with optimism towards finding additional validated drug targets in these hypomethylated regions, but also tied mutations in kinase signaling pathways (such as BRAF) to changes in the epigenome. Fearless prediction: more of these integrative, or "systems biology" studies, will continue to be done (indeed, must be done) as we advance our assault against cancer. In our opinion, not only will mutations or changes in the regulation of the epigenome be tied to mutations or up-regulation of cellular growth pathways and vice versa, but simultaneous changes in aspects like cellular metabolism, immune evasion, and stem cell-like properties will be tied together in a more holistic picture going forward. During the same talk, James "Jay" Bradner from the Dana-Farber Cancer Center gave an outstanding talk (though similar to the one we had seen at ASH 2012) about his work on the probe molecule, JQ-1, and its role in the regulation of the MYC gene, one of the most commonly over-expressed genes in all of cancer (behind only p53). JQ-1 (and presumably chemical matter from privately-held Constellation Pharmaceuticals) blocks a key regulator of MYC activation, bromodomain 4 (brd4), a key regulator of MYC gene transcription. Dr. Bradner's slides showed the pattern of benefit that is now becoming familiar to those of us groupies of epigenetics-that of a flat-line pattern of tumor growth (better yet, death). Dr. Bradner showed some amazing CT scans of a patient with KRAS-mutated lung cancer who experienced a near-total regression of a massive tumor. Dr. Copeland finished the session with a comprehensive discussion of the two targets of focus for Epizyme, DOT1L, mutated in mixed-lineage leukemia (MLL), and EZH2, a very hot gene target that has generated a lot of interest due to its dysregulation in a variety of tumor types (NHL, breast, prostate, colon, gastric and bladder, among others) and which has drawn the attention of a number of large pharmaceutical and biotechnology companies. Again, the shape of Dr. Copeland's Kaplan Meier curves was virtually identical to those of the other speakers-flat-to-downward sloping, rather than right-shifted as has been seen with so many other interventional therapies in oncology. We will be producing a fuller report on the epigenetics space in the near-term.
Early Signs that Epigenetics Holds the Keys to Immunotherapy & Vice Versa
In addition to the separate plenary sessions on immunotherapy and epigenetics, we noted several poster presentations that hinted strongly at the ability to boost anti-tumor immune responses through the epigenetic reprogramming, primarily through the use of hypothmethylating agents. Some of these presentations were in prior notes by us relation to Astex (ASTX, MO) in which tumor specific antigen expression, namely of NY-ESO1 and MAGE-A, in peripheral blood mononuclear cells (PBMCs) was found to increase in response to global gene demethylation in AML/MDS patients treated with SGI-110. In a separate poster, Dacogen induced demethylation in AML cell lines correlated with increased NY-ESO1 and MAGE-A protein expression, further supporting the likelihood that T cell activation plays a role in the mediation of tumor responses by hypomethylating agents (HMAs). Future experiments from Griffiths et al. will measure if tumor antigen specific CD4+/CD8+ T cell responses are in fact elicited by HMA therapy. Meanwhile, a forthcoming prospective study will test the hypothesis in vivo, assessing the combined effect of Dacogen plus the NY-ESO1 vaccine CDX-1401 (CLDX, NC) in patients with AML/MDS. One has to take the good with the bad when it comes to HMA induced gene expression, however. This was evidenced in part in a poster presented by Edward Kadel et al of Genentech (Roche, NC) showing that differential expression of PD-L1 mRNA in NSCLC cell lines was regulated by the level of the promoter by DNA methylation. Induction of PD-L1 expression was most responsive to treatment with Dacogen in cell lines where baseline methylation was high and gene expression low. One initial interpretation of these data might be that DNA demethylation and immune checkpoint activation are antagonistic and that without PD-1/PD-L1 blockade, HMA activity is actually undermined by immnosuppressive mechanisms. Such was the conclusion reached by Garcia-Manero et al in a poster presented at last ASH last December in which the expression of PD-1, PD-L1, PD-L2 and CTLA4 were all induced in the PBMCs of AML/MDS patients treated with low dose Dacogen, or Vidaza in combination with Revlimid (CELG) or vorinostat. On the other hand, it is possible that the induction of PD-L1 expression though HMA exposure acts as primer or homing mechanism for activated T cells. Recall in relation to the plenary talk by Dr. Topalian that tumors responding to nivolumab exhibited relatively higher levels of PD-L1 expression compared with non-responders. Taken together, we believe that future clinical studies of epigenetic therapy used combination with PD-1/PD-L1 antibodies (given perhaps in sequence) will indeed show these regimens to be synergistic in their activities.
In our view, AACR is an exceptional meeting in that it provides the scientific and business community with an opportunity to view the up-and-coming drugs and drug targets of the future. To use a sports analogy, it is akin to being able to see all the college football or basketball teams and their players over the course of just a few days. While there is a lot of information for investors to digest, it also provides incredible opportunities to select the stars of the future, without the distraction of running to numerous sessions to see clinical data. The latter purpose is best served by ASCO, coming in June. However, there is a certain pride (and profit) to be had when one can say "I saw that drug when it was still in Phase II trials" like a promising rookie. We hope the character of the AACR conference never changes.
by Mike King, Managing Director and Senior Biotechnology Analyst, JMP Securities
Biomarkers in Breast Cancer: More Than Just HER2
April 08, 2013 - 11:04 am Posted in AACR Conference Coverage 1 Comments
On Sunday at the American Association for Cancer Research (AACR) 2013 annual meeting, Jose Baselga, M.D., Ph.D., physician-in-chief at the Memorial Sloan-Kettering Cancer Center, presented new data from the Phase III EMILIA trial (Abstract LB-63) that suggested a relationship between tumor biomarkers and efficacy of Kadcyla® (TDM-1, ado-trastuzumab emtansine; Roche/Genentech). Kadcyla is a novel antibody-drug conjugate that comprises a potent microtubule polymerization inhibitor conjugated to the Herceptin® (trastuzumab; Roche / Genentech) monoclonal antibody via a highly stable linker. Kadcyla is designed to take advantage of the targeted nature of the antibody to selectively deliver the cytotoxic agent to HER2+ breast cancer cells. The EMILIA trial evaluated Kadcyla monotherapy versus Xeloda® (capecitabine, Roche) plus Tykerb® (lapatinib, GlaxoSmithKline) (XT) in relapsed HER2+ metastatic breast cancer patients. The positive results led to its regulatory approval in the United States in February 2013. Roche's Herceptin, currently dominates the HER2+ market, with about 85% utilization in front-line HER2+ metastatic breast cancer patients. Although Tykerb is approved in the second-line in combination with Xeloda, about half of U.S. patients are rechallenged with Herceptin plus chemotherapy, leaving Tykerb for later-lines of therapy.
Baselga and colleagues conducted a biomarker analysis as part of the EMILIA study to determine whether variable expression of HER2, HER3, EGFR, PTEN and mutational status of PIK3CA gene impact efficacy of Kadcyla or Tykerb plus Xeloda. Patients in both treatment arms were evaluated according to intratumoral HER2 mRNA levels (at least median HER2 mRNA level versus less than median HER2 mRNA level). Patients with tumors expressing higher levels of HER2 mRNA (median or higher) derived greater overall survival benefit from Kadcyla (34.1 months) versus patients with tumors expressing lower levels of HER2 (26.5 months). In contrast, there was no difference in overall survival benefit in patients treated with Tykerb/Xeloda when stratified by HER2 mRNA levels (24.8 months for high levels versus 23.7 months for low levels). Similar analysis based on mRNA expression levels of HER3, EGFR and PTEN revealed no relationship between these biomarkers and efficacies of Kadcyla or Tykerb/Xeloda regimens. However, the mutational status of PIK3CA was discovered to be associated with improved outcomes when treated with Kadcyla but not Tykerb/Xeloda.
The PIK3CA gene encodes the alpha isoform of PI3K catalytic subunit, which is frequently mutated in HER2+ breast cancers and is thought to represent one of the resistance mechanisms to HER2-targeted therapy. PIK3CA-activating mutations may impact efficacy of anti-HER2 therapies as PIK3CA lies downstream from HER2 in the signal transduction pathway. Therefore, efficacies of these regimens were examined in patients according to PIK3CA-activating mutational status. Indeed, for patients in the Tykerb/Xeloda arm, overall survival of patients with PIK3CA activating mutations was worse compared to patients with PIK3CA wild-type tumors (17.3 versus 27.8 months). In contrast, overall survival appeared unaffected by PIK3CA mutational status in patients in the Kadcyla arm: in patients with mutated PIK3CA Kadcyla improved median progression-free survival (mPFS) from 4.3 months to 10.9 months, and in patients with wild-type PIK3CA Kadcyla improved mPFS from 6.4 to 9.8 months. These data suggest that Kadcyla may be able to bypass a common HER2 resistance pathway that has confounded anti-HER2 therapies and offers a new treatment option to women who would have otherwise not fared as well from other HER2-targeted therapies. Prior data has suggested no significant association between PIK3CA mutation and Herceptin efficacy, similar to what is observed here for Kadcyla, suggesting that this resistance mechanism may primarily have implications for use of Tykerb or other HER2 family tyrosine kinase inhibitors.
These results are thought-provoking and set the stage for future biomarker-driven analyses to guide choice of therapy upon relapse, although it's premature to begin integrating into clinical practice at this time. However, these data could support tighter definitions of patients eligible for therapy with these agents, possibly by raising the threshold for HER2 positivity or by using PIK3CA status to help physicians make an informed decision on whether Tykerb or Kadcyla is a better second-line option for individual patients. The field has grown adept at incorporating biomarker analyses into initial patient diagnosis to guide treatment algorithms, but we are only beginning to understand the potential importance of re-testing patients throughout the progression of disease to further optimize and individualize care.
By: Stephanie Hawthorne, PhD, Director, Kantar Health; Tatiana Spicakova, PhD, Consultant, Kantar Health; and Greg Wolfe, PhD, Senior Consultant, Kantar Health


text:
function action_build()
{
    # Move to the top level of the project to do the build
    # NOTES: since we pass through the user input args to make, so meanwhile
    # all the args will be passed to the main Makefile(e.g. 'CC=clang').
    cd $SKULL_PROJ_ROOT

    _action_prepare
    _action_build $@
}

function action_build_usage()
{
    echo "Usage:"
    echo "  skull build [arg(s)...]"
    echo ""
    echo "Args:"
    echo "  - check"
    echo "  - valgrind-check"
    echo "  - clean"
    echo ""
    echo "Example:"
    echo "  skull build"
    echo "  skull build CC=clang"
    echo "  skull build check"
    echo "  skull build valgrind-check"
    echo "  skull build clean"
}

function _action_prepare()
{
    echo "Generating counters..."
    action_common --metrics-gen || exit 1

    echo "Generating transaction/service IDLs..."
    action_common --idl-gen || exit 1

    echo "Generating configs..."
    action_common --config-gen || exit 1
}

function _action_build()
{
    echo "Building modules/services..."
    exec make $@
}

redpajama_set_name: RedPajamaGithub


text:
Q: windows vnc via ssh to kvm guest - connection failed I've a headless CentOS6 running KVM and I want to configure a guest via vnc. The problem is my working machine is Win7.
I created a guest using command:
sudo virt-install --name=c6-64 --disk path=/var/lib/libvirt/images/c6-64,size=8 --vnc --vcpus=1 --ram=1024 --cdrom=/tmp/CentOS-6.0-x86_64-bin-DVD1.iso --os-type=linux --os-variant=rhel6

So the vnc is listening on 127.0.0.1:5900.
No I want to connect to the vnc from Win7 machine. I tunnel 5900 from localhost to the server using putty, ssh connection is successful. However, when I try to connect using ultravnc or realvnc connection gets refused and in /var/log/secure on the server I can only see:
error: connect_to 10.0.0.2 port 5900: failed.

Can someone please tell me what am I doing wrong? I just need to connect to the guests without installing vnc server inside them and only ssh access is not sufficient (windows guests too).
Thank you for any idea.

A: "So the vnc is listening on 127.0.0.1:5900"
The vnc should probably be listening on the IP of the headless Cent host.

A: Use Xming and SSH with putty using X forwarding.  Then on the server, run vncviewer 127.0.0.1:5900, and it will forward that to your Windows 7 machine and give you a VNC window.
That way, you don't have to forward multiple ports for multiple VMs, since the VNC client will be running on the server.

redpajama_set_name: RedPajamaStackExchange


text:
Ending the Culture of Illness through Healthy Eating
Bluebird Bio's Gene Therapy for Blood Disease Wins European Approval
Hi Marley Raises $8M From Investors to Streamline Insurance With AI
Grail's Cook Steps Down, Former Juno Executive Bishop Named CEO
Brad Feld
Managing director, the Foundry Group
Jeff Bussgang
Jeff is a General Partner at Flybridge Capital Partners whose investment interests and entrepreneurial experience are in consumer, Internet commerce, marketing services, software and wireless start-ups.
Jeff currently represents the firm on the boards of BzzAgent, ClickSquared, DataXu, digitalArbor, i4cp, Mall Networks, Ready Financial, SimpleTuition, and Transpera and was previously a director at Brontes Technologies (acquired by 3M), go2Media, and PanGo Networks (merged with InnerWireless).
Prior to joining the firm in January 2003, Jeff co-founded Upromise (acquired by Sallie Mae), a loyalty marketing and financial services firm and was an executive at Open Market, an Internet commerce software leader. Jeff was recently appointed to serve as an Entrepreneur in Residence at Harvard Business School's Arthur Rock Center for Entrepreneurship. His popular blog on helping demystify the venture business for entrepreneurs, "Seeing Both Sides", can be found at www.seeingbothsides.com.
Jeff holds a BA in Computer Science from Harvard University where he graduated magna cum laude and an MBA from Harvard Business School where he was a Baker Scholar and a Ford Scholar
Progressive Business Leaders Meet for "Davos on The Charles" Policy Summit
The annual World Economic Forum confab in Davos, Switzerland is famous for gathering business and policy leaders to discuss the big issues of the day. Entrepreneurs, venture capitalists, and private equity... Read more »


text:
Rajkumar Rao's Upcoming Movie Has No Title!
Rajkumar Rao's upcoming film has no title. Yes, this is true! Directed by Vikramaditya Motwane the poster is absolutely untitled. But, if we minutely notice the poster, we can see that it contains all other details only except the name of the movie.
In the poster, we can see a blurry figure of an individual who is, probably, looking outside. The background is, however, a visual of the entire city. With some necessary information, the poster reads 'A PHANTOM PRODUCTION' with other details as well.
Probably, this very thing immediately grabs the viewers' attention. Surprisingly, the most interesting thing about the poster is that it is mysterious. The film is slated to be screened at Jio MAMI Mumbai Film Festival on October 26. Though it is an untitled poster, yet a temporary name 'Trapped' has already been given to the film just in order to continue with a seamless screening.
In an innovative move, the team without any delay has released the poster of its untitled film. Yet they are still in a go, to unfold the final title of the movie. Indeed, it is a 'first of its kind' move, isn't it?
Apparently, after Udaan and Lootera, this is the next movie for the director Vikramaditya Motwane. Not only this but also the film marks to be the third association for the duo; Vikramaditya Motwane and Rajkumar Rao. Evidently, their former two projects were; first the critically acclaimed movie Queen and the second being Newton, the forthcoming black comedy.
However, the premiere is Rajkumar Rao's third entry at MAMI Film Festival. Rao has showcased the National award winning film known as 'Shahid' along with 'Aligarh'.
For more updates about the movie, stay tuned with us.
TagsRajkumar Rao
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How to Read Piping and Instrumentation Diagram (P&ID)?
Equipment Location Index. Piping and Instrument Diagrams shall be divided into equivalent intervals (each in 50 mm) either in length or width. The intervals shall be designated with numbers from 1 to 23 in length and alphabets from "A" to "P" in width.
www.piping-engineering›Piping layoutPiping Layout Drawings Abbreviations and Legends. Whenever you start reading a piping drawing or document, you can see many abbreviations on these drawings/documents. Many abbreviations are common and are regularly used in the drawings but few of the abbreviation are new and unique for a particular drawing. Sometimes it happens..
Instrument Abbreviations Used in Instrumentation Diagrams (P&ID) Custom Search. Typically instrument abbreviations used in P&IDs consist of two letters: the first indicating the process variable and the second indicating the instrument/controller function. For example, the instrument abbreviation "PI" denotes a "Pressure Indicator".
Piping and Instrumentation Diagram. In the process industry, a standard set of symbols is used to prepare drawings of processes. The instrument symbols used in these drawings are generally based on International Society of Automation (ISA) Standard S5. 1. 2. The primary schematic drawing used for laying out a process control installation.
Mar 08, 2013PROCESS AND INSTRUMENTATION DIAGRAM The Piping and Instrumentation Diagram (P&ID), based on the Process Flow Diagram (PFD), represents the technical realization of a process by means of graphical symbols for equipment and piping together with graphical symbols for process measurement and control functions.
ENGD320 Process Piping Drafting I Learn with flashcards, games, and more — for free.
Piping and instrumentation diagram. Superordinate to the piping and instrumentation flowsheet is the process flow diagram (PFD) which indicates the more general flow of plant processes and equipment and relationship between major equipment of a plant facility.


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Our Vision: To move Louisiana onward by delivering a safe and innovative multimodal transportation and infrastructure system.
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Efficiency — Ability to accomplish goals with the minimal use of resources.
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Q: Is this charger suitable for a 18650 battery? I'm not really into Electrical stuff and this is the only place where I can ask this question and get a nice and described answer, basically I'm lookin for a good Charger/Discharger for a couple of 18650 3.7v Lithium batteries and I came across this:
AccuPower IQ338 Fast Charger and Analyzer Tester for Li-ion NiMH NICd Rechargeable Batteries
It looks good to me but I read that it apply a charge voltage of 4.13V, is this ok in my case?

A: Yes, it is OK. The picture actually shows an 18650 cell being charged.
You might be confused by the 3.7 V and 4.13 V.
The fact is that the voltage of Li-Ion based cells (like 18650 cells) changes when it is charged and discharged.
3.7 V is sort of a "average" voltage for the cell when in use.
A reasonable low (empty) voltage for a Li-Ion based cells is 3.6 V
A reasonable high (fully charged) voltage for a Li-Ion based cells is 4.2 V
So the charger's 4.13 V is a good choice. Charging to a higher voltage (like 4.3 V) is possible but puts more stress on the cells so they wear out sooner. I think 4.13 V is a good compromise.
Learn more about this at Battery University.


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This 2100 square foot surf shop in North Miami Beach carries surfing, skateboarding, skimboarding, and wakeboarding equipment and supplies.


"The perfect pickled onion should be a balance of briny and sweet," says NoMad barman Leo Robitschek. "It should be fully pickled while still retaining a slight crunch." To achieve this,Robitschek creates a pickling liquid that preserves and elevates the flavors of the onion and adds some extra spice, which he says brings out the umami notes and brininess. Make a batch for your next round of Gibsons.
Combine all the ingredients except the onions in a pan. Bring to a simmer, then remove from heat and allow the liquid to reach room temperature. Once cooled, pour the liquid over the onions in a large jar and cover for 2 weeks.


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Shakespeare Festival
About GVSF
GVSF Staff
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Join GVSF
Outreach Performances
Bard to Go: Lovestruck
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MEASURE FOR MEASURE (2016)
Featuring Amber Miller and Michael Pollock
(Read more about Measure for Measure)
Bard Beyond Borders
Bard Beyond Borders is a special 25th anniversary project of the 2018-2019 Grand Valley Shakespeare Festival. Theatre artists from two different international festivals/companies will travel to Grand Valley to perform in the Linn Maxwell Keller Black Box Theatre. The artists will also provide workshops and public and class discussions and presentations along with their special performances.
Sizwe Banzi Is Dead
By Athol Fugard, John Kani, and Winston Ntshona
Direct from Nassau, The Bahamas
January 31, February 1 at 7:30 p.m. and February 2 at 2 p.m.
Linn Maxwell Keller Black Box Theatre, Thomas J. and Marcia J. Haas Center for Performing Arts,
Allendale campus
More information and free ticket reservation: (616) 331-3200
Limited Engagement! Ticket Reservations Strongly Recommended!
Athol Fugard's Sizwe Banzi Is Dead, one of the most critically acclaimed productions presented in The Bahamas, was originally a featured part of the 2014 Shakespeare in Paradise Theatre Festival. This production reunites the director and his original cast members for a limited engagement as part of the Grand Valley Shakespeare Festival's 25th Anniversary Season.
Play synopsis
Written and set in apartheid era South Africa, Sizwe Bansi Is Dead confronts the struggles faced by people of color during the time and tethers them to broader questions of identity and human worth. Set in a photography studio, the plot follows a man who comes in to have his photograph taken
Reviews of the Original Bahamian Production
"An extraordinary play with extraordinary performances by Dion Johnson and Mark Humes. Brilliantly directed by Philip Burrows. SEE THIS PLAY!"
"GO SEE THIS AMAZING PLAY.... I was in awe at the work of the director, Philip Burrows and Actors, Dion Johnson and Mark Humes... So worth seeing."
"A masterful performance. Bravo!"
"I saw this last night, and I LOVED it. The performances by Dion Johnson and Mark Humes were excellent under direction by Philip Burrows."
"A Broadway caliber production."
Page last modified April 25, 2019
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