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Dorm Food Do-Over
When you were a student and you couldn't make it to the dining halls, maybe you dined on a smorgasbord of foodstuffs that came from a science lab (spray cheese, anyone?) instead of a farm.
And maybe that sounds appealing in your early 20s, but the faux glow eventually wears off. Yes, for most of us, the memory of homemade dorm food is best left in the dorm—preferably in a drawer next to the Twinkies and Ritz crackers.
But what if those lackluster memories were replaced by more elegant and creative interpretations of the dorm food we knew and (sort of) loved? Like mac 'n' cheese made with real cream and tender, smoky bacon and eaten with a linen napkin in your lap, not a plastic fork at your side? Or how about a towering crown of cappuccino ice cream, marshmallow fluff, and bittersweet chocolate sauce to replace that microwaved marshmallow and chocolate sandwich that you used to call a s'more?
Consider the following recipes your dorm food redux—a remodeling of food from your Denison days. Let's raise a glass of really cheap wine (out of a sense of nostalgia, of course) to the beautiful ways in which these five graduates have given dorm food a much-needed makeover.
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Best of News
Members of the Secteur du Rail Aunts 'Kuluna' fight with members of... News PhotoDemocratic Republic of the Congo,Horizontal,Kinshasa,Law,People,StreetPhotographer AFPCollection: AFP 2014 AFPMembers of the Secteur du Rail Aunts 'Kuluna' (street children gang) fight with members of the Likonzi Kuluna (in the background) on December 14, 2012 in a street of Lingwala, north of Kinshasa. The modus operandi of kuluneurs is the following: either in broad daylight or at night, a pack of martial arts practitioners (called pombas) armed with clubs, machetes and other blunt objects raid and occupy a city square wherein they seize from passers-by and street vendors any valuable they can lay their hands on. Victims who resist are hacked with machetes, clubbed or stabbed. Some victims have died from injuries sustained in those kuluna raids and many a warlord kuluneur have has been gunned down by the Police dIntervention Rapide (PIR). AFP PHOTO / JUNIOR D. KANNAH (Photo credit should read Junior D. Kannah/AFP/Getty Images)

subset: commoncrawl


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Publisher's Description+
WinImage is a disk-imaging suite for easy creation, reading, and editing of many image formats and file sytems, including DMF, VHD, FAT, ISO, NTFS and Linux. The disk image is an exact copy of a physical disk (floppy, CD-ROM, hard disk, USB, VHD disk, etc.) or a partition that preserves the original structure. With WinImage in place, you can recreate the disk image on the hard drive or other media, view its content, extract image-based files, add new files and directories, change the format, and defragment the image. All this and more is delivered in one intuitive user interface that enables imaging right out of the box. The program has many utilitarian uses at home and in the office. As a serious PC user, you probably have tons of old but still useful floppy disks. As a hard-disk backup solution, WinImage allows you to save hours and even days restoring a system and configurations on a machine that has experienced a hard-disk crash.
Version 8.0.8 adds VHD support.


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October: Domestic violence awareness month
Davis at Legislature: EMS hearing brings grave concerns
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Hall Red Angus ranch honored as Pioneer Breeder of the year
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Singing with unique harmony, the Four Freshmen will bring back the sounds of favorite music from the 50s and 60s in the first concert of the North Platte Concert Association's 2015-16 series at 7:30 p.m. on Tuesday, Oct. 13, at the Neville Center for the Performing Arts. ...More
Award-winning filmmaker Donald L. Vasicek ("The Sand Creek Massacre") urges people who were sexually molested and/or raped by Erwin Charles Simants to report it to their local law enforcement officials immediately. ...More
Seven teenagers from the ag college at Curtis were seriously injured after midnight Wednesday when their pickup went off the road in the hills east of Wellfleet. ...More
A Purr-fect Pasta dinner will be held Friday, Oct. 9 to raise money for Paws-itive Partners and show off the talents of local celebrity chefs. ...More
Randy and Maggie Houpt of North Platte redeemed their $1 million ticket in the Nebraska Lottery Powerball on Wednesday. ...More
A rundown of entertainment in North Platte and Lincoln County. ...More
A North Platte woman was allegedly assaulted overnight Tuesday and not found until an hour before daybreak. ...More
Wednesday will be Edy Patterson Day in North Platte, Mayor Dwight Livingston declared Tuesday night at the beginning of the North Platte city council meeting. ...More
Sen. Mike Groene of North Platte was the second-most conservative state senators during the 2015 legislature, according to a report Tuesday by a statewide fiscal conservative group. ...More
Nathan Abernathy, 21, was sentenced Monday to 300 days in jail for receiving stolen property and theft. ...More
When Paws-itive Partners and veterinary clinics first sponsored a "Love My Cat" month, no one knew there would be many more. ...More
Monica Vanarsdall of North Platte received an official looking envelope recently in the mail, along with a cashier's check for nearly $2,000. ...More
On Friday at approximately 7:42 p.m., an officer met a parent who was concerned that her 15-year-old son may have had a sexual encounter with a 21-year-old North Platte woman. ...More
Julius Reed, 24, was sentenced to 3-5 years in the Nebraska Penitentiary Monday for being a felon in possession of a firearm and making terroristic threats. ...More
In the aftermath of the shootings in Oregon, here's part of an article we published in January 2013 about treating mental illness. ...More
The Nebraska Game and Parks Commission has received a $150,000 grant from the National Fish and Wildlife Foundation to provide habitat for Monarch butterflies. ...More
Curing a requested rate hearing Thursday, the Nebraska Public Power District board of directors took comments from wholesale customers who are looking at a 3.8% wholesale rate increase....More
The Central Nebraska Public Power and Irrigation District will lower Jeffrey and Johnson lakes on Sunday and Monday (Oct. 11-12) to allow workers to do some unplanned maintenance work upstream....More
The credit reporting bureau Experian recently reported that an unauthorized party gained access to a database that contained personal information of an estimated 15 million T-Mobile customers and potential customers, including 4,790 Nebraskans....More
Lake McConaughy's elevation was at 3,257.1 feet on Monday morning, about 20 feet higher than a year ago, with inflows that were about 160 percent of normal....More
Some rare finds were reported by Reid Cummins earlier this year during a paleontology Passport in Time project he and Barb Beasley led near Ardmore, S.D....More
Nebraskans have yet to recognize the magnitude of human trafficking in their home state, officials said Friday at an international conference in Lincoln....More
Members of rural emergency medical services departments throughout the state expressed concerns about and gave advice to lawmakers Friday about securing the future of volunteer rescue services....More
GREEN fundraiser tops $120,000
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Cross country: Lincoln County scores two medals
VB: Sandhills, South Loup defeat Maxwell
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Representing himself, a man carries his child support dispute to the Nebraska Court of Appeals. The supreme court reviews the judge's actions in another Lincoln County divorce dispute... Also... dealing with the real cause of mass shootings... complete account of the North Platte city council meeting... upcoming events of note... thoughts about the power of the press, and more.
Get the full story only in this week's North Platte Bulletin print edition
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Square Enix and United Front Games have just confirmed three new downloadable content packs that will soon be released for their recent Sleeping Dogs game, including the second story-based add-on called Zodiac Tournament.
Sleeping Dogs came out back in August and delivered a pretty impressive open-world experience that focused on undercover cop Wei Shen as he tried to take down the Hong Kong triads.
After releasing plenty of bonus content for the game, as well as the first story-based DLC, in the form of Nightmare in North Point, developer UFG and publisher Square Enix have confirmed three new add-ons for the game.
The first is the Zodiac Tournament Pack, which adds a brand new island off the coast of Hong Kong, where Wei Shen will participate in different fighting competitions.
Besides this story-based add-on, two other DLCs will came out in the near future, in the form of the Drunken Fist one, which adds a drunken fighting style, and a Gangland Style one, which allows Wei Shen to get certain tattoos that augment his abilities.
Check out the descriptions of these add-ons below, via CVG.
Zodiac Tournament Pack:
Join Wei Shen for the fight of his life in the second gameplay-extending add-on pack. Invited to an exclusive tournament on a hidden island off the coast of Hong Kong, Wei must overcome the best-of-the-best as he takes on fighters from across Asia in a fight to the death. The Zodiac Tournament invites you to become the dragon and unleash your fists of fury!
An exclusive new island off the coast of Hong Kong, featuring multiple themed fight arenas, numerous new enemies, bosses and story-extending cutscenes
Two new unlockable outfits featuring new looks and powerful new fighting moves
Drunken Fist Pack: With the Drunken Fist pack, Wei unleashes this exclusive fighting style. While in combat, filling the face meter will enable Wei to drink from a flask of potent alcohol and perform unique special moves and powerful counters unavailable to the sober man!
Rediscover a classic fighting style with this unique outfit!
Sway like a drunkard, hit like a mule...
Enter the Drunken Stance and perform special moves and counters
Gangland Style Pack: Get Wei Shen freshly inked-up in a trio of tattoo schemes in this alternate costume pack. Topple the Triads in street style with a Japanese Yakuza, Russian Mafia, or Maori Mongrel Mob tattoo, each with their own buff.
Yakuza style: Painstakingly applied with the traditional 46 needle irezumi brush, this tattoo will slow your heart rate by 50%
Russian Mob style: A complete history on your skin, increasing gun accuracy by 50%
Mongrel Tribe Style: Leave no doubt which side of the law you are on with a 40% melee damage increase
The add-ons have yet to receive an actual release date, but you can expect UFG and Square Enix to confirm one soon enough.


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In the battle for dominance in worldwide retailing, there's not much contest: Wal-Mart Stores is the winner with room to spare. But, despite its moves into retailing outside this country, most of its sales volume is generated in this country, and that's at the time retailers elsewhere are consolidating and driving volume from outside their home countries. Is there much prospect that Wal-Mart could relinquish its lead? Let's find out in a moment, but first let's take a look at who the ...
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Opinions split as Legislature looks again at changing class-size rule POLL
NAPLES - A proposal that will loosen the requirements of Florida's class-size amendment unanimously passed a Senate education subcommittee this week and is closer to becoming a reality.
Under the bill, schools would be allowed to add up to three more students in prekindergarten through third-grade classes and up to five more students in core courses in grades four through 12 following the state's October student counts.
The schools still would be considered in compliance with Florida's class-size rules that voters declined to change in November.
The bill, proposed by Sen. David Simmons, R-Altamonte Springs and chairman of the Senate Pre-K-12 Appropriations Subcommittee, also redefines what a "core course" is — the class-size amendment applies to core courses only.
Under the proposed legislation, core courses would be defined as:
■ Language arts/reading, mathematics and science courses in prekindergarten through third grade.
■ Courses in grades 4 through 8 in subjects measured by state assessment at any grade level.
■ Courses in high school subjects that are measured by state assessment at any level.
■ Classes required for high school graduation and not measured by state assessment, excluding extracurricular courses.
The current class-size amendment, which Florida voters passed in 2002 and declined to change in a November vote, limits the number of students in core classes like math and English to 18 in prekindergarten through third grade; 22 students in fourth- to eighth-grades; and 25 students in high school.
This week's passage of the bill from the subcommittee was good news to the Collier County School District, Chief Operations Officer Michele LaBute said.
"It's better for our students. We won't have to keep shifting students to avoid going over the limit," she said.
The class-size amendment, which Florida voters passed in 2002, limits the number of students in core classes like math and English to 18 in prekindergarten through third grade; 22 students in fourth- to eighth-grades; and 25 students in high school.
LaBute said if, for example, a school has five third-grade classes, it would allow the school to accept 15 more kids after the October count, without having to rearrange classrooms or hire teachers.
The big fear that district officials have talked about is the scenario in which one new student comes into a school and classes that have been together for months would have to be split up to accommodate the additional student so that the class-size limit is adhered to.
The change, she said, would also result in a cost savings for the Collier County School District.
"I hope the Legislature passes it," she said. "We are asking our legislators to support it."
Not everyone is happy with the proposed legislation. The Florida Education Association, which represents the state's teachers, is against the bill.
"This bill seeks to achieve what opponents couldn't in the November election," wrote Mark Pudlow, spokesman for the Florida Education Association, in an e-mail.
In November, supporters failed to pass Amendment 8, which would have allowed schools to measure class size on a school average rather than by individual classrooms. Amendment 8 failed to receive the necessary 60 percent approval, which meant the class-size rules have to be followed as originally written.
"This bill isn't solely about giving school districts flexibility. If it was, we would have supported it, as we have in the past with legislation focusing on flexibility," Pudlow wrote.
Pudlow said the bill was driven by budget concerns and not the legitimate goals of the class-size amendment.
"To truly see the scope of courses not covered by the proposed changes one need only see the DOE (Department of Education) analysis that notes in 2010-11, there were 849 courses defined as core content. Under the proposed bill, there would be 288 core courses," he wrote.
The courses that would be dropped include foreign language, honors and advanced classes at the middle and high school levels, as well as those not required for graduation.
"This bill is all about saving money, not meeting the goals in the state constitution of reducing class size," Pudlow wrote. "The Legislature is thumbing its nose at the voters who affirmed those goals in November."
LaBute said the district hopes the decision on the bill is made quickly because the Collier County School District will be looking to hire teachers this spring.
"Right now, we are looking to implement with the current law," she said. "The sooner we can know, the better."
__ Connect with Katherine Albers at www.naplesnews.com/staff/katherine-albers/
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October 6, 2015
WHITESBURG, Ky. (WYMT) - Dozens of people came together in Letcher County for the Action Against Substance Abuse march and Rally.
Several churches organized the event along with Operation UNITE.
The rally featured many guests from judges to pharmacists, who prayed for the battle against drugs.
They say they believe that the only solution to the region's drug problem is God.
"We believe that God is the answer, and that Jesus is the way. We've got to do something through a unified effort in our community, said worship leader," Frank Holbrook.
Resources for help or recovery were available at the rally for anyone in need.
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January 20, 2011
Ballerina Ashley Akacich performs a jump during a run through of a solo that will be part of The Dance Center's upcoming performance of Snow White. Tuesday, January 18, 2011
Stories this photo appears in:
Marquee: Dancers present a re-imagining of 'Snow White'
Ballet dancers of the The Dance Center will perform a piece researched and envisioned by instructor Idalee Hutson-Fish.
Seven dwarves, an evil queen and a young princess will soon fill the stage to tell the fairy tale of "Snow White" through ballet.
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It was build by the Syrian astronomer
Andronikos Kyrrestes,
in the second century BC, as a weather vane and water clock, and stands
inside the Roman Agora. Its external
depicts faces of the eight winds.
ΒΟΡΕΑΣ (North).
He blows the cold north wind
through a large shell.
ΚΑΙΚΙΑΣ (North East).
He throws a basket of hailstones
on those below.
A young man bringing
fruits and grain.
ΕΥΡΟΣ (South East).
An old man with beard
is wrapped in a cloak.
ΝΟΤΟΣ (South).
Bearer of rain, he empties
a pot of water.
ΛΙΨ (South West).
He holds the stern of a ship
as he steers.
ΖΕΦΥΡΟΣ (West).
A semi naked young man
scattering flowers.
ΣΚΙΡΩΝ (North West).
He scatters glowing ashes
from a bronze vessel.
© 2003 - 2015 Ellen Papakyriakou/Anagnostou. All
rights reserved.


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INDIANAPOLIS, IN, AUG 29 - Monster Yamaha Tech 3's Ben Spies led the first six laps of his second home grand prix en route to a career best second in front of nearly 63,000 sun-scorched fans at Indianapolis Motor Speedway.Starting from his first ever pole position, Spies jetted into the lead and controlled the pace until the seventh of 28 laps when Repsol Honda's Dani Pedrosa used the speed of his RC212V to motor past at the stripe.By then Pedrosa had run up four fastest race laps-the third, fourth, sixth, and seventh-and would add three more, eight, nine and 11. Finishing the 11th lap Pedrosa had 2.8 secs. in hand and he'd stretch it to over 5.5 secs. before slowing to finish with a 3.575 secs. margin of victory."Spies was quite, was maybe half of one second ahead, and he was pulling very, very strong," Pedrosa said. "But I could pick up, pick up and get over - ahead of him. And finally I try to do my rhythm and I was able to escape and do a good pace. So I am very happy, pleased with my bike. It was a fast bike in the straight and it was going well, also, in the corners. So good feelings."The third victory of the season was a milestone for Pedrosa: It was the first time since he joined the senior class in 2006 that he'd won more than two races in a year. And it was Spies best ever finish in a season in which he has two podiums and a pole position."Yeah. I mean, we can't complain, you know," Spies said. "We came in and did better than I thought we were going to do. We got the pole yesterday and got out and had a good start today and led some laps. Didn't set the world on fire, but we, you know, we had a good pace. I just wasn't fast enough when Dani came by. His bike was working good, and he had good grip. We had a good setup, too; it just wasn't fast enough. And I tried as hard as I could and didn't make too many mistakes. Saw that we had a gap to third and, you know, just tried to manage it and ride as hard as I could."Spies was never truly under pressure from Fiat Yamaha's Jorge Lorenzo. The world championship leader didn't have the pace of the front-runners and had to settle for third, more than three seconds behind Spies. It was the first time this year that the Majorcan had finished below second place."Yeah, I must not be disappointed, no, but I'm not happy with my race," he said. "I didn't ride so well. The start didn't help me to make better. That's why I didn't feel so good with my physical condition, no? The third lap I was tired and I was not able to make the same pace as in practice. Anyway, this our worst result, and I think for Misano we will come back again, and we will see."Still, he leads Pedrosa in the world championship by 68 points, 251 to 183, after 11 of 18 races.Fiat Yamaha's Valentino Rossi made a run at Lorenzo after passing Andrea Dovizioso (Repsol Honda) on the 20th lap. But Lorenzo was never in serious danger and Rossi came fourth, one better than Dovizioso.Ducati Marlboro's Nicky Hayden was alone in sixth. Hayden lost his left knee slider early on and couldn't fully use his left side in the tracks 10 of 16 left hand corners."I'd been fairly quickly, Friday, Saturday morning, this," Hayden said. "Started on the front row. Dani did a 40 and I wasn't going to do 40's today in that heat. I thought I could at least put up a fight for the podium. I'm not saying I would've got on there. I think I could've ran in that group, but it was just a long miserable, boring race. They took off and I was just trying to just keep my gap on Simoncelli."Still, Hayden had a better race than his teammate Casey Stoner, who crashed out of sixth on the eighth lap.San Carlo Gresini Honda's Marco Simoncelli closed to within a little over a second on Hayden, but finished seventh. His bigger worry came from behind. Rizla Suzuki's Alvaro Bautista made a run that came up short by .085 secs.Pramac Racing Ducati's Aleix Espargaro was alone in ninth, as was fellow Spaniard Hector Barbera (Paginas Amarillas Ducati) in tenth, and Rizla Suzuki's 11th place finisher Loris Capirossi.The final two finishers were recovering Honda riders. In his first race since breaking his back warming up for the June 20 British GP, Hiroshi Aoyama finished 12th."Under the given conditions here at Indy it was quite hard to finish the 28 laps," Aoyama said. "I had to fight in every single lap. I could stay with the other riders, but didn't want to risk anything."De Puniet said Indy was more difficult than Brno, where he'd raced only four weeks after breaking his leg. The stress of that race caused his leg to swell up and kept him off his feet for three days afterwards."Honestly this was the most tough race for me since the beginning of the year, even more demanding than Brno!" he said. "We tried to get the most from our bike and I even tried to change my riding style, but at the end I could not find my pace."The non-finishers, other than Stoner, were Marco Melandri, Colin Edwards, and Mika Kallio. Each had a story. Melandri (San Carlo Honda Gresini) started the race as the youngest rider ever to reach 200 GP's, but it wasn't to be a happy day. Melandri was pushing hard when he lost the front end on the third lap while in a strong seventh position.Edwards chose the harder Bridgestone rear option, but found he had no edge group. With higher temperatures on Sunday, Edwards was hopeful that the extra-hard rear would be better at the end of the race. He never got that far. Instead he pitted to change to the hard rear on the twelfth lap. But after five more laps he retired."I was riding on the limit but way off the pace so I pulled in for the softer tire and did a few laps and my lap times were immediately better," he said.
Kallio (Pramac Racing Ducati) crashed on the 19th lap while chasing Simoncelli and Bautista.
1.Dani Pedrosa (Honda)
2. Ben Spies (Yamaha)
3. Jorge Lorenzo (Yamaha)
4. Valentino Rossi (Yamaha)
5. Andrea Dovizioso (Honda)
6. Nicky Hayden (Ducati)
7. Marco Simoncelli (Honda)
8. Alvaro Bautista (Suzuki)
9. Aleix Espargaro (Ducati)
10. Hector Barbera (Ducati)
Henny Ray Abrams | Contributing Editor
Abrams is the longest-serving contributor at Cycle News. Over the course of his 35-some years of writing and shooting photos, he's covered events from MotoGP to the Motocross World Championship - and everything in between.


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The results from the World Disabled Ski Championships in Anzere, Switzerland are in. The U.S. team took seven medals including three firsts.
Results of the inaugural Disabled World Cup downhill race in Breckenridge, CO.
Sarah Will wins again for the second straight day and Kristof leads a 1-2-3 US sweep in stand-up class at the Chevy Truck Disabled World Cup In Breckenridge, CO.
Overall results from the Chevy Trucks Disabled World Cup slalom race held Thursday Dec. 9.
Go to skiingmag.com
Go to nastar.com
Go to warrenmiller.com
Copyright © 2015 Cruz Bay Publishing, Inc. an Active Interest Media Company.


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Houston County Courier - Local News
Stories Added - March 2009
Copyright 2008 - Polk County Publishing Company
HCMA Announces Holy Week Schedule
Houston County Courier - March 2009
The Houston County Ministerial Association (HCMA) will gather as united Christians during Holy Week.
This year Holy Week will be April 5-12.
It begins on Sunday, April 5 when the scripture readings for the day will focus on Jesus' triumphal entry into Jerusalem.
This is where people gathered awaiting for a new King to lead them away from and victoriously over the Roman Empire.
So the local people placed palm branches on the road, their garments as well, in honor of the new King, Jesus Christ.
As the week unfolded though, Jesus disappointed the people because instead of conquering the empire he gave up his own life. What kind of king does this?
This is the story of Holy Week.
HCMA invites the public to attend the united worship services to discover together once again the story of victory over death for our Lord, Jesus Christ.
The following is the schedule:
The preachers for each service will be Monday, Rev. Tim Allen, Tuesday, Chaplain Sam Cupa from the State School, Wednesday Father Dan Gonzalez, Thursday, Brother Earl Harris and Friday, newly ordained Rev. Jack Chase.
Each day the worship services will start at 12 p.m. and by 12:30 p.m. those attending will be invited to eat a quick lunch at each respective church so that you can be back at work by 1 p.m. All are invited.
Finally, the story ends with a sunrise service on Easter Sunday, April 12 at 7 a.m. led by Dr. Charles Allen and Rev. Jim Tom Ainsworth at Camp Tejas in Weches.
The next meeting of the Association will be April 8 at Wayside Bible Church at 10:15 a.m. A prayer breakfast gathering will be at the Hill Top Café starting at 9 a.m. All pastors you are invited to join the group.
Polk County Publishing Company
Copyright 2008
Contact Us: firstname.lastname@example.com
Call us at - (936) 327-4357
Webmaster: Gregg Faith


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Ghost Recon Online was part of Ubisoft's Wii U lineup in 2011, but there was no word of it at E3 2012. Why? Due to the whole team being hard at work on the PC version.
According to a Ubisoft spokesman:
"Our focus has been entirely on delivering a great launch on PC. … Achieving that has been an all-hands-on-deck effort for the team this year. We're looking forward to seeing what we can do on other platforms like Wii U once we're on solid ground with the PC launch."
Ubisoft has mentioned this before: the Singapore team responsible for the game is fine-tuning it on PC, since PC environments are easier to test with. The team will then move on to the Wii U version once the PC version is released and stable.
Currently, Ghost Recon Online's PC debut is planned for sometime in 2012.
Eurogamer: Ubisoft Uncertain On Ghost Recon Online's Wii U Release Date


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Trending Searches: FY2016 Budget | Taxes | Parks | Library
Homeless Intervention Program (HIP)
The Department of Social Services offers short-term rental and mortgage assistance to households experiencing an unforeseen financial crisis. The Homeless Intervention Program (HIP) is a state-funded program used to assist eligible households. Interest-free loans are provided for temporary rental, mortgage and security deposit payments for those who meet program criteria and have income at 80 percent of area median income or lower. This program is open to residents of Prince William County, Manassas City and Manassas Park.
Housing counseling is an important aspect of the HIP program. Participants in the program are required to create and complete self-sufficiency goals in order to facilitate long-term financial independence. Participants must work with a housing counselor during the assistance period. Together the counselor and participant will identify areas of need and develop a goal plan. Participants may be required to attend budgeting classes and credit counseling.All mortgage assistance applicants must first contact Marjorie Leon at Virginia Cooperative Extension at 703-792-4713. For all mortgage loans given, Prince William County will place a lien against the property.
Eligibility Criteria
If you believe you meet the criteria, prescreening by phone is the first step in applying for the program. Prescreening interviews are conducted on the first and third Wednesdays of each month from 8 – 11 a.m. The number to call for prescreened is 703-792-7648. The HIP Committee determines if the criteria are met and either an appointment is scheduled with a housing counselor or a denial letter is mailed.
For additional information review the attached brochure: Homeless Intervention Program (HIP) Brochure


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CHICAGO (DETROIT FREE PRESS) - Prince Fielder, Austin Jackson and Torii Hunter all homered as the Detroit Tigers won their third straight in this four-game series in Chicago, 6-2, tonight over the White Sox.
Anibal Sanchez pitched six shutout innings, allowing six hits, just one for extra bases, and a walk while striking out five on 101 pitches.
Fielder had three hits and three RBIs. Jackson had two hits and Hunter had a pair of hits and scored twice. Rookie Hernan Perez had two singles.
Miguel Cabrera missed his second consecutive game with a sore left hip flexor.
The Tigers put a three-spot on the board in the first inning. Jackson opened things with a single to left, but was erased on Hunter's fielder's choice. Matt Tuiasosopo, hitting in the third spot for the second consecutive night, walked.
Fielder then smashed a 1-0 pitch to deep right-center for a three-run shot, his 17th of the season.
Then with two out and nobody on in the second, Jackson hit the first pitch he saw down the leftfield line for his sixth home run of the year.
After Jackson grounded out to begin the fifth inning, Hunter hit a high fly ball to left just over the wall for his ninth home run of the season.
Lefty John Danks (2-8) allowed six earned runs on 11 hits and a walk while striking out three in 6 1/3 innings.
Meanwhile, Sanchez (8-7) stranded runners and first and second with two outs in the fourth inning by getting Conor Gillapsie to ground out to first. Then in the fifth, Josh Phegley singled and Alejandro De Aza (three hits) doubled with one out. But Sanchez forced an Alexei Ramirez groundout and an Alex Rios fly out to end the threat.
Bruce Rondon entered in the seventh and yielded a leadoff single to Dayan Viciedo (three hits). While striking out Phegley, Rondon threw a wild pitch, allowing the runner to reach second. De Aza then drew a walk and Ramirez then hit an RBI single to left.
Drew Smyly struck out the side, but allowed a single in the process, in the eighth. Luke Putkonen gave up a leadoff homer to Viciedo in the ninth, but got the next hitter, Phegley, to fly out. Phil Coke then came in to face a lefty, De Aza, who singled to center. The Tigers then summoned Joaquin Benoit, who got the final two outs.
Detroit added another run with a two-out rally in the sixth. Don Kelly found the hole on the left side for a single, then Perez hit a grounder in the hole at short, but Ramirez's throw was not in time. Then Alex Avila, who had just one hit off lefties in 37 at bats entering tonight, singled to right to drive in a run.


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Thursday, August 20, 2009
Boombalatti's Ice Cream, Wilmington NC
Boombalatti's, a funny name for something that's neither a burger, nor a brew, but one amazing ice cream place. The address is 1127 Military Cutoff Road, Wilmington North Carolina. You'll find it across the street from the Mayfaire Mall.
They have a great selection of ice creams, and they say they are all made fresh daily. It took a while to decide. I had the two scoop sundae for only $3.75. My two scoops were Peanut butter cup and chocolate cream pie, with hot fudge, whipped cream and peanuts. Heaven in a plastic bowl.
Stop in and visit them when you're in town. You'll be glad you did. Better than Cold Stone, and a whole lot cheaper.
Update- April 2, 2010
We went back the other day and it was every bit as good as the last time. Excellent ice cream at good prices. If you live near them, patronize them and keep them going. If you don't live near them, take a road trip.
Posted by Chris Forman at 9:21 PM
Labels: Wilmington
2 comments:
I have been here several times. The ice cream is just out of this world. i am sure many moms in the bizymoms Wilmington community would like to share their view on Boombalatti'sReplyDelete
I'd love to hear their comments. Boombalatti's is amazing.ReplyDelete
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Fraud Prevention Unit
Welcome to the Fraud Prevention Unit of the U.S. Consulate in Guayaquil. Our principal mission is to safeguard U.S. borders by detecting and stopping fraud in applications for U.S. passports, Consular Reports of Birth Abroad, immigrant visas and nonimmigrant visas. We accomplish this critical goal by training Consular Section staff on fraud detection, maintaining close cooperation with U.S. and Ecuadorian law enforcement agencies, and deploying our staff of highly trained investigators to conduct interviews and investigations. The Fraud Prevention Unit appreciates your cooperation. If you have information concerning fraud that you wish to share with us, you may do so by contacting us through our e-mail address email@example.com. Your identity will be kept confidential.
Beware of persons who say they can obtain a visa for you, whether they are charging you money for the advice or offering the advice as a friend. The U.S. Consulate in Guayaquil does not regulate or endorse individuals or businesses that offer advice or assistance with the visa process. No one can guarantee the issuance of a visa to you. Visa eligibility can only be determined at the time of the visa interview. All U.S. government forms are free.
WARNING: Many visa applicants lose money or are permanently barred from the United States after committing fraud on the advice of so-called "visa consultants". The consequences of committing fraud during the visa or passport application process are extremely serious. The Fraud Prevention Unit in Guayaquil maintains a zero tolerance policy towards fraud and it works in conjunction with U.S. and local authorities to enforce it. If you commit fraud, not only will you lose the benefit that you are seeking, but you may also have to pay hundreds of thousands of dollars in fines and you may even go to jail. The Fraud Prevention Unit, working closely with the American Citizens Services Unit, the Immigrant Visa Unit, the Nonimmigrant Visa Unit, the Department of State's Bureau of Diplomatic Security, and the Department of Homeland Security, aggressively pursues fraud cases, referring individuals as appropriate for prosecution under U.S. and/or Ecuadorian law.


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Quebec AM | Feb 14, 2013 | 3:58
Horse meat on Quebec's menu
Horse meat is considered a cheaper form of meat in Europe. A scandal has erupted in the past few weeks after horse meat was found in burgers that were labelled as beef burgers. Horse meat has since been detected in other prepared foods in Europe. While eating horse meat is largely taboo in Britain and some other countries, that's not the case in Quebec. Allison Van Rassel visited Le Pied Bleu restaurant in Quebec City where you can find "bavette", on the menu.


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« What Medicinal Chemists Really Make |
| A Complete Diversion: Purple Compounds »
Posted by Derek
We know what clinical trial success rates have been like for the last twenty years or so (hint: not so good). Are things turning around, or not? This Nature Reviews Drug Discovery piece takes a look at the 2008-2010 data. It's not necessarily reassuring:
At present, however, Phase II success rates are lower than at any other phase of development. Analysis by the Centre for Medicines Research (CMR) of projects from a group of 16 companies (representing approximately 60% of global R&D spending) in the CMR International Global R&D database reveals that the Phase II success rates for new development projects have fallen from 28% (2006–2007) to 18% (2008–2009), although these success rates do vary between therapeutic areas and between small molecules and biologics.
There were 108 Phase II failures in 2008-2010, and for 87 of those we have a stated reason. Half of those were good old lack of efficacy, another 19% failed on safety grounds, and the rest failed for "strategic reasons". The best guess there is that the compounds seem to have been targeting areas where there was already competition, and they didn't differentiate themselves enough from the standard of care to be worth continuing. That's worth thinking about in the context of the arguments about "me-too" drugs. To hear some of the industry's critics tell it, there shouldn't be any such failures at all, since they seem to believe that even most marketed drugs really don't differentiate themselves from their competition as it is.
Nearly 70% of those 108 failures, by the way, were in four therapeutic areas: cardiovascular, CNS, metabolics, and oncology. (What we don't have are the failures adjusted for how many drugs were taken into the clinic in the first place in those areas). CNS and oncology are traditional high-risk areas, of course, and I think that a lot of the metabolics failures were in diabetes. That's a tough field - big market, but pretty well-served, making efficacy versus the standard of care a high bar to clear, and this while the FDA's safety requirements have gotten very stiff indeed.
But cardiovascular - that's interesting, since that area has traditionally had one of the better trial success rates. Perhaps that one is also suffering from the standard of care being pretty good (and often generic, or soon to be). So the high-success-rate mechanisms of the old days are well covered, leaving you to try your luck in the riskier ideas, while still trying to beat some pretty good (and pretty cheap) drugs. . .
Update: it's been suggested that some of these "strategic" failures are a sign of what happens during merger/acquisition activity. Could be, but you'd have to run these down company-by-company. I'll see if I can contact the authors of this paper about that idea. . .
Comments (38)
+ TrackBacks (0) | Category: Cardiovascular Disease | Clinical Trials
1. Lacerta Bio on May 10, 2011 7:47 AM writes...
The "Strategic" failures are what really disturb us. How many innovative programs are being shelved because the forecasts don't hit some arbitrary hurdle? Or because of new management with different priorities?
2. Still Scared of Dinosaurs on May 10, 2011 8:13 AM writes...
Are these trials that missed their endpoints or drugs that were discontinued? Killing a drug is a big deal but in big pharma if you don't miss on a Phase 2 trial or two you're not trying hard enough.
I agree about strategic failures, expecially when it's because a placebo-controlled trial failed to show a certain percentage response determined by market research. Don't kill the drug until you tell me why you expected that response rate in this population.
3. Jose on May 10, 2011 8:37 AM writes...
Yeah, I'll be waiting with bated breath for "the terrible complexity of the global community to fight the terrible complexity of disease."
"The Rise of Backyard Biotech"
4. johnnyboy on May 10, 2011 8:37 AM writes...
Low-hanging fruits... Amid the general panic about the ongoing increase in development failure rate and decrease in new drug approvals, I think it would bear stating, or repeating, that these are completely normal - they are actually built into the concept of drug development. Since new drug approval is predicated upon a drug needing to be better in some way than what is already on the market, and since the market is packed with the fruits of 100 years of drug development, with drugs that won't go away, it only stands to reason that new, better drugs will get harder, and harder, and harder to develop as time goes by.
Which means that as time goes by, MORE resources have to be devoted to drug development in order to just keep the success rate constant. Since companies are slashing their research budgets across the board, any sane person can see that the success rates will continue going to the dogs, for years to come.
5. johnnyboy on May 10, 2011 8:59 AM writes...
@ Jose (#3): oh LOL. I love the fact that the main example in the article for the great usefulness of social networking, in this 'New Paradigm' of drug development, is... email debates over what color the capsules should be - for a drug that hasn't even passed phase 2.
But, as the author tells us, "that's the way science ought to work". He should know, as he's written about extreme body modification and DIY robots...
I suggest that we take a breather from discussions of the on-going disintegration of the pharma industry, and instead have a discussion of the on-going disintegration of the Atlantic Monthly...
6. Hap on May 10, 2011 9:25 AM writes...
There are things that social media and increased cooperation can do, but if no one knows the critical things and has the equipment or knowledge to figure it out, then the mass of people still won't have the knowledge or capability to figure it out.
The problematic part in drug development is in trials, and that's the part that garage biotechers don't have access to, either. (although why doesn't the prospect of Facebook-run clinical trials fill me with joy?) I guess that anyone with a potential drug would be bought out before trials, but that seems like a nightmare for the VC/drug company people, and the uncertainty still lies ahead and is not assuaged by the use of social media.
Making cool things isn't nearly as hard as making drugs.
7. drug_hunter on May 10, 2011 9:34 AM writes...
I've said it before: until we understand disease biology waaaay better than we do now, we aren't going to make a lot of improvements in Pharma / Biotech. It follows that all right-thinking chemists should be devoting themselves to doing whatever they can to help biologists (and clinicians) sort out disease biology. Chemistry is hard and fun and challenging and all that, but it is rarely the rate-limiting step.
8. MoMo on May 10, 2011 10:19 AM writes...
Drug Hunter,
Why is it up to chemists to help the biologists do their job understanding disease states? Less than a hundred years ago you had us blood-letting and fought the notion of infectious diseases until Louey Pasteur, as the babes called him, a chemist fixed the problems.
We chemists understand the biology a lot better than you give us credit for, and we are always pointing out your mistakes. then and now.
We need less cryptic biology of course, so get get to work!
What we need are More Molecules (MoMo) not MoBo (more biologists).
And if you think the modern pharmaceutical industry was baswed on biology-study the history of the greats-Pfizer, Cyanamid, Merck-
All launched and prospered under chemists!
9. pete on May 10, 2011 10:43 AM writes...
@8 MoMo
Well put EXCEPT, the rise of biologicals blows a grand canyon-sized hole in your diatribe.
Take a Biologist to lunch today :)
10. lynn on May 10, 2011 11:03 AM writes...
@8 momo -
I'm not going to take up the biologist-chemist argument... but we microbiologists consider old Louis to be one of ours. I know he started out as a chemist [and he taught physics and had a degree in mathematics]- but he's considered one of the founders of microbiology. I'd say the best drug discovery comes from communication and cooperation between biologists and chemists.
11. Still Scared of Dinosaurs on May 10, 2011 11:32 AM writes...
To what extent is the problem caused by cases where a company understands the biology just fine, it's just that this understanding leads them into someone else's patent area? What they actually put in the clinic is the best they can do with technology they have access to?
12. MoMo on May 10, 2011 11:38 AM writes...
Pete and Lynn,
No doubt about those biologists! I love em' to death unless they start talking about extreme kinetics, molecular mechanisms or ghost impurities that mangle their results. Then they must be dealt with sharp and swift! BAM! POW!! No Mercy!
And then there are 10 biologists to every chemist in the room so we have to scream to be heard.
And then there is the 10:1 ratio in graduate schools-killing my funding chances just because biology is perceived as less difficult.
Lets go back to Chemists running the Pharma Industry....
Just like the old days.....
13. Rick on May 10, 2011 11:40 AM writes...
Hey wait! What about the argument that it's all the FDA's fault??? Whenever the discussion of increasing costs and failures in drug discovery and development comes up, someone usually chimes in with their fresh-from-the-can "Blame the FDA" diatribe by now. Somehow this must be the FDA's fault...
14. hal on May 10, 2011 11:41 AM writes...
The Atlantic article describes where BigPharma's strategic failures need to go, to small, cheap virtual companies that can advance the product by outsourcing strategically to where it's suddenly worth acquiring as the development risk's been wrung out. Many such products/companies will fail, and financing isn't easy. New indications might be found (even after approval, see FDA's potential orphan database) for such molecules and companies. We're doing this now, but without money, won't be for long.
15. hal on May 10, 2011 11:42 AM writes...
16. Hap on May 10, 2011 12:04 PM writes...
...and if you're paying chemists and biologists virtual startup money for the rest of their careers to make money for VCs and big pharma management, I suspect you'll run out of chemists and biologists.
While people at drug companies sure don't know everything about how to make drugs, they probably know a lot, and since neither the outsourcing targets nor the garage bio people nor the VCs and management know how to make them, it's hard to see where that knowledge is going to enter the process. We're missing something, and we don't know what it is (else drug companies wouldn't be in this bind), but going without that knowledge (because it isn't worth pharma, and us, paying for) seems like poking your eyes out because you can't afford glasses.
17. hal on May 10, 2011 12:12 PM writes...
Hap, we spent venture (and other) money to manage chemists and biologists and keep them employed. Hiring them wouldn't be 'virtual.' Pharma is doing a good job firing enough to staff the contractors we use. You are correct that the knowledge isn't freely available, but Pharma strings us along in "strategic partnerships" and gets the R&D done with OPM and their insights. Doing the same on the academic side keeps them driving the bus. Watching for the patent cliff. Damn glasses.
18. Hap on May 10, 2011 12:51 PM writes...
No, I assumed that somebody was paying them, and for the time being there's plenty of people to work in the world, so you can get what capabilities you can't make at home or in lab easily. I'm assuming, though, that if being in a drug development CRO or university drug development group is the only way for chemistry and bio drug people to be employed (which seems to be the way that drug companies as well are going), that there won't be many people to do those jobs in the long run. The benefits primarily accrue to others, so the risk doesn't fit the reward for people other than management.
The capacities that both big pharma and the build-from-scratch model seem to not value are the capacities that would seem to be important for developing drugs. They aren't working as well as they either should or were, but they are important. Unless there's a way to capture the information temporary arrangements of drug developers make, that information will likely be lost, and so most of the business will be blind (because there is no capacity to develop that information internally over the long-term).
There's room for lots of people to play, but everyone is hoping the diamonds are in the shallow end of the sandbox, and they probably aren't.
19. Cellbio on May 10, 2011 12:57 PM writes...
My thinking aligns more with johnnyboy than drug hunter, though of course reasonable points can be made for the advantage of knowledge, but it is hard to reconcile with the past few decades. Knowing about disease mechanisms, targets, or human or mouse genetics has not helped keep approval rate steady. Perhaps without this knowledge, our older empirical methods (today's chemical biology to not be a dinosaur)would have had an even higher failure rate, so I can't wholly discount disease biology knowledge. But, one can point to examples that illustrate an understanding of mechanism is not associated with immediate therapeutic gains. Sickle-cell anemia is a good example. Molecular defect know long ago (1954?)does not lead to tractable med chem program.
On the other hand, my couple of decades has seen areas of opportunity change from wide open to well served, with programs having to change midstream from statistical benefit over placebo to bettering standard of care that works very well. I think the contribution of our prior successes to our current tough road to approval is not trivial at all, and influences many aspects of our business, most painful of which is the merger and lay-off cycles we are living through (dying through).
I think it also manifests itself in biotech taking on SM work, and pharma bringing in biotech. Both sides see the limitations to pursuit of certain paths with a dedication to one technology, and can no longer afford to abandon lines due to failure of technology fit, while both sides were willing to do this a while back.
When I started, there were only a few areas we did not pursue due to the markets being well served, including coagulation, blood pressure, analgesics. Now the prospects of bringing forth new meds in Psoriasis, Rheumatoid arthritis and asthma are daunting. Do others not have this same experience in your therapeutic areas? Either due to successes or numerous failures that explore and discard hypotheses from disease knowledge?
20. Linda Pullan on May 10, 2011 1:18 PM writes...
Assuming the proportion of drugs by therapeutic area are about the same for the top companies as the industry as a whole, a quick calculation of the number of failures in this report for each therapeutic area against the total number of compounds in Phase II for each, says that the failure rate was highest for alimentary and metabolism with 23 failures here out of 343 compounds in Phase II. CV has the second highest rate relative to number of compounds in development and CNS and Oncology are tied, as there are 508 compounds in Phase II for oncology and 410 for neurology.
21. Mike Sturgess on May 10, 2011 4:08 PM writes...
Although this data is quite depressing all around, a more detailed comparison by therapeutic area with the Phase II successes would have been valuable . 29% of failures due to "strategic' reasons seems high, but as has already been stated this is the price that is paid for trying to find a better patented drug vs an off patent existing treatment. This is the business side of the development equation and depends upon many factors that may, or may not, change during the development process.
Of greater concern to me are the other 71% of failures - safety and insufficient efficacy. Both of these could and should be better evaluated earlier in the process. Insufficient efficacy suggests a greater need for biological evaluation of the target and the drug prior to Phase II. Of course such studies would delay the program and add costs, potentially allowing a competitor to reach the market first.
22. Oldtimer on May 10, 2011 4:11 PM writes...
Unedifying slanging matches between chemists and biologists won't find new drugs, you need each other. Re "the good old days" Sarett ran Merck R&D successfully but so did Vagelos after him, you can't argue from the particular to the general. PS what happened to Cyanamid?
23. Cellbio on May 10, 2011 4:52 PM writes...
Mike, isn't Ph2 biological evaluation of the target and drug, specifically the drug? I don't think animal models yield predictive info. Is there more to add which really informs the probability of outcome in Ph2? And is it knowable in the timeframe of pipeline decisions? To be successful, we have to move forward with good decisions that future results prove right or wrong. Too high of a demand on certainty of clinical success freezes organizations and prevents generation of Ph2 data that, in my opinion, are the first true test of our assumptions about a target or pathway in human disease.
Hi Linda! (your secret admirer)
24. pete on May 10, 2011 4:58 PM writes...
MoMo & Oldtimer
I like Chemists (...wouldn't lurk around here unless I did). Just standing up for us Bio-logicals in the crowd :)
25. RespiSci on May 10, 2011 5:14 PM writes...
The article mentions "well conducted Phase II clinical trials" but should include well designed and crafted too. I've been involved with drugs where in a single study, the drug may miss its primary efficacy endpoint, but hit other endpoints, causing us to review the clinical study design, altering for example, patient inclusion/exlusion criteria, or the dosing regimen. No matter how solid your preclinical information, there are things that you just can't learn from in vitro or animal studies. And unlike preclinical work, where you can repeat and retweak an experimental design relatively quickly and easily, not so with clinical studies. Instead, these are very public and costly failures. "Public" by registering on clinicaltrials.gov but also, let's face it, often with company press releases. For some small biotechs a Phase II study may be their "one shot on goal" and they don't have the resources to go back and try again, although the drug in question may in fact have true potential.
26. barry on May 10, 2011 6:14 PM writes...
re: Cellbio #19
Some areas that used to be wide open are now regarded as well served (and one can no longer run a Phase II trial against placebo, but only against the existing standard-of-care).
Others that had been regarded as well-served sometimes come back into play. Osteoporosis drug candidates e.g.that were sidelined because the bis-phosphonates owned that market should be advancing now that we know more about the shortcomings of those older drugs.
27. Cellbio on May 10, 2011 6:47 PM writes...
Hi Barry,
Good point that situations are fluid. I think that until a compound has significant post-market experience it is too early to give up because of perceived market closure. I wonder about your example. Won't the new entrants face tougher regulatory environment with dictates to follow the outcomes recently noted for current therapy and show a better profile for ONJ or femur fractures, for example. I think so (though maybe have the wrong BP issues). Not that this doesn't present a clear, defined opportunity, but one with even greater demands for outcomes to be called a success in Ph2: efficacy and reduced side-effects compared to known agents. Today's regulatory demands are a change from prior regulatory environments where new drugs did not have this high a burden, and new mechanisms could be marketed with hints or beliefs that things would be superior. Not a bad thing in my opinion.
28. Anonymous BMS Researcher on May 10, 2011 8:38 PM writes...
I'm a biologist myself, but I work with a lot of very smart chemists. Most of them understand the biology a heck of a lot better than I can follow the chemistry, actually, but of course neither side can do drug discovery without the other.
Rather than get into a chem-vs-bio slanging match, let's all throw stones at the MBAs :-)
29. Kenneth on May 10, 2011 11:12 PM writes...
Since most research is trial and error in nature and only occasionally is innovation found, would a better management system which provides up to date trial info in real-time identify winners and losers much quicker and provide cost-avoidance and reduced waste. Identifying a better mousetrap has always been difficult and unrewarding. The inability to overcome market saturation is directly proportional to the history of data and results analysis which have built fences around areas where limited thinking is the result. When drug development is about helping the human condition and not about money will progress be made. Can the current approach to drug development and its associated costs ever be challenged as long as someone is willing to pay the bills?? And how long will this situation go unchallenged? A new paradigm is required if progress is to continue in quantum steps!!!
30. Alan Crowe on May 11, 2011 5:07 AM writes...
When the result of a clinical trial is that the drug did nothing, it doesn't mean that literally. All we know with certainty is that the number of patients who benefited is roughly balanced by the number of patients who were harmed.
Guessing that zero patients benefited and zero patients were harmed is usually a good guess, but it is still a guess. Perhaps in years to come a more refined diagnosis will split the disease into two subtypes and a failed drug will come back to life as a valuable treatment for one subtype. Doctors will not be celebrate because such a drug is a diagnostic nightmare. You have to get the diagnosis of the subtype correct because the treatment actively harms patients suffering from the other subtype of the disease.
We already have that problem with strokes. Yes, your patient has a stroke, but you need to do a brain scan to find out it is the clot kind of stroke of a bleed-into-the-brain kind. Do you treat with a clot-buster or a clotting promoter? Getting it the right way round is a matter of life and death.
What are we up to with depression and schizophrenia? Does any-one think these are single illnesses? Perhaps they are single illness from a social point of view or from the view point of a general practioner trying to pick a consult to refer his patient to, but it is implausible that they are single illnesses from the biochemical point of view.
Perhaps the disordered thinking of schizophrenics is sometimes due to too much X and sometimes due to too little X; we might even have useful drugs that boost X and others that reduce X and we have discarded them all because we don't know what X is and cannot subtype our diagnosis into the too much and too little variants.
Obviously I am an outsider, looking in on the drug discovery business. As an outsider it is very striking how gnarly, intricate, and detailed the biochemistry side of things is. And as an outsider it is striking how vague and broad-brush the diagnostic/DSM IV side of things is. They don't match up.
All the insiders are talking the language of success rates: the problem is drugs failing. In the current state of medical knowledge it makes more sense to talk of diagnostic finesse: the problem is that all our diseases are too heterogeneous for our detailed chemical interventions. Don't say: the drug failed, Do say: the diagnosis was too vague.
31. Great Molecular Crapshoot on May 11, 2011 7:14 AM writes...
Phase II typically represents the first encounter of the disease model with reality.
32. Biotech Author on May 11, 2011 8:43 AM writes...
I wonder if in some way we're putting the cart before the horse in this debate.
To me, the real clue is the high rate of failure of safety and efficacy-related points in the Phase II failures. This doesn't lead me to think that "Oh, the biologist/chemist/toxicologist, et al, got it wrong" - Instead, this leads me to wonder where in the earlier stages of development (pre-clinical, Phase O, Phase I), we went wrong. Did we select endpoints that were simply unrealistic given our data to that point?
Maybe some of these Phase II candidates never actually should have gone into Phase II - they should've been halted earlier. Personally, I've sat in Big Pharma formulation meetings and listened as various scientists expressed extreme skepticism that the molecule would hit any of the endpoints, but they were over-ruled / out-concensused(?) by various directors in RA, Biz Dev, etc. who stated, "Well, we never make a decision on ending a development program until after Phase II trials. Until then, let's proceed."
On the other hand, I've sat in meetings with small biotechs and start-up pharmas as they struggled to understand why their drug - with dramatic successes in Phase I trials - stumbled in Phase II, only to find out that their CRO botched the monitoring jobs at trial sites, and lots of "good results" had to be tossed because the site data lacked provable integrity (I'm not saying the investigator was bad, just that a cynical reviewer could cast a LOT of aspersions on the reliability of the data). And thus, they recorded that Phase II failed.
I recognize that we are in this sort of catch-22 right now, where the more we learn about disease, the interplay of genetics, and so on, the more difficult it gets to hit acceptable levels of safety and efficacy. Indeed, I suspect that if we were to really run a lot of the drugs that were approved 10, 15, 20 years ago through trials today using the knowledge, the technologies, the techniques and the expectations we have now, some of those previously approved medicines would not make the cut.
The answer - it seems to me - is not to blame the science, but to look earlier in the pipeline and in the organization.
Looking earlier in the pipeline and improving how we make "go/no-go" decisions in the organization are how the firms I noted in my latest book were successful. Perhaps these strategies won't work for everyone, but it seems as though they do help some firms improve their odds to get to market.
33. MoMo on May 11, 2011 9:16 AM writes...
Don't worry, we jettison anybody who starts fights these days with each other, no time for drama when you are making and testing molecules!
What happened to Cyanamid? It was one of the world's best at chemistry and natural products until it merged with Pfizer recently. Need I say more? Sure!
Then all the good chemists ran screaming with severance packages or "retirement" parachutes fit for immortals and now it is mere shell.
It will never be the same again.
But here's the story when it was a chemical company and blossoming into a fledgling pharmaceutical comapny. Its president said, in 1938
" You may come up with nothing, but you may discover a single drug that will conquer even one major disease, then the public will be well served and our company will prosper"
These are the kinds of leaders we need today, not those bent on cash flow and revenue projections and when they emerge I am sure you will read it here.
We will all be waiting.
34. johnnyboy on May 11, 2011 11:30 AM writes...
@32: You are right in your last point, but you are also stating the obvious. Clearly, Phase 2 failure rates would be better if there had been better go-no go decision-making earlier in the process, but that's a bit of monday-morning quarterbacking. In this day and age, a drug candidate will have gone through a LOT of go-no go decision points before it gets to Ph2, and the people making the decisions were most likely doing them to the best of their knowledge at the time. The fact that better decision-making is necessary is not a secret; the difficulty is in figuring out HOW to improve this decision-making.
As to management types pushing bad drugs candidates along - I think that's a fact of life in pharma. It doesn't pay to be a pessimist in business - managers are mainly evaluated on how good a cheerleader they are. I don't think any manager's career can be helped by being the one who decides to kill a program (his self-respect maybe, but not his career). It's much better for his career to push it along, meet his numbers, and let the guys down the road be the ones with the bad news. Upper management sets quarterly objectives for total numbers of candidates having to move through the various checkpoints, and failing to achieve the numbers means that you're failing - even if your candidates have a much better chance of development than those of the department who meets their numbers with lemons. Is this a good model for managing drug development ? Probably not, but if someone knows of another one, i'd love to hear about it.
35. cynical1 on May 11, 2011 12:57 PM writes...
One of the things I've observed over the past decade or so is the increase in Phase II studies using an approved drug in an indication for which it doesn't have a prayer, like using a statin for asthma or a nuclear receptor agonist in alzheimers. In particular, the big companies are doing this far more than the small guys.
Obviously, I don't have numbers but I have seen just so many stupid, retarded trials being done on approved drugs. Are those trials part of the analysis that was done? (I don't have access.) If they are, I would probably suspect that more than a small percentage of the failures were just based on poor science.
We had a name for those things growing up: A Hail Mary. Where is Roger Staubach when you need him?
36. caner_man on May 11, 2011 9:52 PM writes...
Then there is GSK killing SRT501 in a phase II cancer trial despite 1) there were no reported kidney trials in the earlier succesful diabetes trial 2)according to GSK, some of the cancer patients wanted to and did keep taking SRT501 while the trial was suspended before canceled outright.
GSK just said that the efficacy/cost trade-off wasn't worth it.
Of course, SRT501 was essentially just resveratrol, not the synthetic compounds currently in several trials.
37. Student on May 12, 2011 1:08 AM writes...
@ Jose (#3) This is interesting. The advantage of big pharma is that they get multiple shots at generating a drug (which, in their minds they hedge by cutting programs early). The advantage of small startups is that they are willing to take what big pharma doesn't.
1.) What executives hedge away as risk, small startups pick up as high reward/yield potential. i.e. A company kills something after phase II trials that isn't as positive as they had hoped (but not negative...)
2.) What their executives ignore as small market share, small companies see as low competition markets.
I'm sure Big pharma sees these small companies as ants scouring for leftovers. But if you've ever left your picnic unattended for too long you'd know how fast that food becomes inedible without realizing it. (and I use inedible as opposed to eaten because if enough people are taking on certain targets a big company just won't risk going after it)
38. ED on May 12, 2011 5:13 AM writes...
Interesting piece from David Grainger on this problem, and his take on it.
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Hazel Cottage is a particularly attractive farm property with lovely views and parking, recently extended and updated to provide a good standard of accommodation throughout. The cottage is ideal for family groups or couples looking for a cosy, comfortable retreat within easy reach of local beaches and the surrounding countryside.
South Down Farm is situated in a quiet, secluded position, within an Area of Outstanding Natural Beauty, surrounded by National Trust farmland with access through a delightful valley to Soar Mill Cove and the South Devon Coast Path. Salcombe and Kingsbridge are three and five miles away respectively, whilst the village of Malborough, with its pubs, small shop and post office, is just a 2-3 minute drive or 30 minute countryside walk.
Coast & Country Cottages can not be held responsible for the accuracy of the position of the property shown on the map, as these are powered by Google - if you have any concerns about the location of the property then please call our team on 01548 843773 who will be able to advise you.
LOCATION The cottage is at Southdown Farm, a development of former barns, farmhouse and cottages in a quiet, secluded position (within an Area of Outstanding Natural Beauty), surrounded by National Trust farmland and an ideal location, therefore, for wildlife enthusiasts, walkers and families. There is quick and easy access through a delightful valley to Soar Mill Cove and the South Devon Coastal Path (passing Hazel Tor en route) whilst the village of Malborough with its two pubs, village Post Office, garage/mini supermarket is just 1.5 miles away. Salcombe and Hope Cove are within a short 10 minute drive.
VIEWS Lovely views across fields and neighbouring farmland from the kitchen and first floor bedrooms.
ENTRANCE Steps (6) lead down from the parking area to the cottage entrance and lobby. Stairs lead immediately up to the first floor accommodation.
SITTING ROOM From the entrance an open corridor leads into a cosy sitting room with two large comfortable leather sofas, armchair, TV/DVD player (with good selection of DVDs), MP3 player/radio, and glass door to a secluded courtyard with gate through to the garden. The sitting room leads into the kitchen/dining area with access also to the ground floor shower room.
KITCHEN/DINING ROOM A new and well presented kitchen with lovely slate flooring, high vaulted roof with cross beams and double doors out to the spacious terrace and garden. Fitted Shaker-style units, four-ring electric hob, electric oven and grill, dishwasher, washing machine, microwave, fridge/freezer and mini hi-fi. Dining table with six chairs.
SHOWER ROOM Off the kitchen is a new shower room with corner cubicle, power shower, wash-hand basin, w.c. and heated towel rail.
BEDROOMS Three in total. On the ground floor is a light and sunny room with double bed, bedside units, drawers, wardrobe and chair. On the first floor is a second double bedroom with wooden bed, bedside units, fitted wardrobe, drawers, window seat and TV. In addition there is a twin room with two single beds, drawers and fitted wardrobe. N.B. All duvets, pillows, bed linen and towels (except those for the beach) provided.
SNUG Also on the 1st floor is a small 'snug' room, ideal for children, with sofa/day-bed.
BATH/SHOWER ROOMS In addition to the ground floor shower room (above) is a new, fully tiled family bathroom - on the first floor - with bath, shower (over), wash hand basin, w.c., heated towel rail and airing cupboard.
OUTSIDE To the rear of the cottage is a large terrace with lovely views, picnic table and built-in barbeque - steps lead down to a mature garden with good-sized lawn, trees and shrubs. Further courtyard area with cobbled stones and additional picnic table plus SHED/UTILITY ROOM with tumble dryer and garden furniture..
PARKING Ample parking for 2-3 cars plus a boat trailer on the gravelled area driveway in front of the cottage.
OTHER INFORMATION Gas fired central heating and hot water. Telephone available for local and incoming calls only (limited mobile 'phone reception at property). Wood laminate and slate flooring on ground floor with carpet in most first floor areas. A Riverford Organic Holiday Box is supplied with compliments of the owner, for each week long booking.
Reviews by
1 month ago
"An excellent place to stay, great facilities in cottage in wonderful countryside surroundings. Location is superb for exploring South Hams. Highly recommended "
Coast & Country Cottages' reply:
Thank you for your kind review of Hazel Cottage near Salcombe. We were so pleased to hear that you found Hazel Cottage to be such an excellent place to stay and you enjoyed its countryside location. We were delighted to hear that you found this property to be such a wonderful base for exploring the South Hams! We hope to welcome you back to this beautiful area again soon.
1 month ago
"First time in Salcombe for us all and we had a fantastic week. Hazel Cottage provided a wonderful, relaxing haven and we have all thoroughly enjoyed our stay - thank you!"
1 month ago
"Lovely comfortable cottage. Thank you for the leaflets and mags too. The area is great, enjoyed Hope Cove. Loved cafe. Gara Rock lovely walk from East Portlemouth."
4 months ago
"Very nice comfy cottage in great location. Nice garden with views."
Coast & Country Cottages' reply:
Thank you for your kind review in respect of your recent stay at Hazel Cottage near Salcombe. We were so pleased to read your comments and do hope you enjoyed your holiday. Looking forward to welcoming you back to the South Hams very soon. The Team at Coast & Country Cottages
5 months ago
"Lovely cottage in a beautiful area we all enjoyed our stay."
Coast & Country Cottages' reply:
We were very pleased to receive your review regarding your chosen property, Hazel Cottage, Malborough near Salcombe. Your feedback is greatly appreciated - thank you. We do hope you choose to stay with us again in the very near future. The Team at Coast & Country Cottages
1 year ago
"Lovely cottage with a fantastic location. Spacious but cosy at the same time. So nice to have coastal path on your door step. The walk to Soar Mill Cove was lovely - shame the sand has gone!"
1 year ago
"Was ideal for our family of 2 grandparents, 2 adults, 2 children and a dog. The cottage was well equiped and the use of the garden was such an asset."
3 years ago
"Thank you, we enjoyed our stay very much and would recommend the cottage as it is in an ideal quiet seclusive position, a leisurely 20 minute walk through fields (and cows) to Hope Cove beach and a short drive to North and South Sands beaches and ideal for short visits to Salcombe, Kingsbridge and Dartmouth."
3 years ago
"I have always found the staff in the Coast & Country office most helpful. We have been booking properties through them for many years."


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Lauryn Chun, Olga Massov
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Following traditional kimchi-making seasons and focusing on produce at its peak, this bold, colorful cookbook walks you step by step through how to make both robust and lighter kimchi. Lauryn Chun explores a wide variety of flavors and techniques for creating this live-culture food, from long-fermented classic winter kimchi intended to spice up bleak months to easy-to-make summer kimchi that highlights the freshness of produce and is ready to eat in just minutes.
Once you have made your own kimchi, using everything from tender and delicate young napa cabbage to stuffed eggplant, you can then use it as a star ingredient in Chun's inventive recipes for cooking with kimchi. From favorites such as Pan-Fried Kimchi Dumplings and Kimchi Fried Rice to modern dishes like Kimchi Risotto, Skirt Steak Ssam with Kimchi Puree Chimichurri, Kimchi Oven-Baked Baby Back Ribs, and even a Kimchi Grapefruit Margarita, Chun showcases the incredible range of flavor kimchi adds to any plate.
With sixty recipes and beautiful photographs that will have you hooked on kimchi's unique crunch and heat, The Kimchi Cookbook takes the champagne of pickles to new heights.
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Notebook: Vikings' draft gave Christian Ponder 'a pretty big smile'
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EDEN PRAIRIE, Minn. -- Christian Ponder was at the Metrodome draft party with teammate Adrian Peterson when the Minnesota Vikings used their top draft pick on a player who can help both of them.
"Both of us cracked a pretty big smile," Ponder said on Wednesday, six days after the Vikings selected Southern Cal left tackle Matt Kalil at No. 4 overall.
Kalil -- who will make his Vikings practice debut when rookie camp begins on Friday --is expected to start immediately at left tackle. That'll move Charlie Johnson to left guard, upgrading the protection unit if everything goes to plan.
And no one would benefit more from that than Ponder, whose struggles as a rookie were magnified by an increasing tendency to stare down the rush, rather than keeping his eyes downfield.
"It is huge," Ponder said. "A lot of time last year, it didn't necessarily have to do with the protection. A lot of times I wasn't comfortable getting to my third, fourth reads, checking the ball down. Instead of just checking it down when a guy is wide open, I'd just run.
"That's something I have to get away from. It's easy to break the habit. It's just going to make it so much better having full confidence in the protection. Offensive line is looking good. They got stacked up pretty quickly and they've got a lot of depth now. I'm excited about that as a quarterback."
On board
Johnson said he had "no problem" with moving to guard -- a move offensive line coach Jeff Davidson began discussing in September.
"Like I told Coach Davidson, Coach (Leslie) Frazier, anybody who asked me about it, I just want to win," Johnson said. "Last year was not very good. I wasn't used to that and I don't want it to happen again. So, if they feel that this is the best thing to make our team better, then I'm all for it."
Johnson dismissed a question about whether he's better-suited to guard -- "My skill set is for playing football," he said -- but pointed out he spent time there during his days with the Indianapolis Colts.
"This has been something I've been dealing with since I got into the league, going on six years now," Johnson said. "It just happened to be the past couple of years I was at tackle. But the first couple years, it was wherever I was needed was where I would play. So I've dealt with it. It's not a problem."
More work
A year ago, the NFL lockout wiped out all offseason practices. The collective-bargaining agreement that emerged from that work stoppage reduced offseason work going forward, with the Vikings' organized team activity practices scheduled to begin on May 29.
So, players can't do on-field work with coaches for several more weeks. But Ponder said he's been watching a lot of film, throwing with teammates after each conditioning session and brushing up on the playbook to get a head start before OTAs.
"We watched a lot of stuff from last year," Ponder said. "Just seeing myself on film, there's so much I can do better. I get so frustrated watching myself last year, watching myself escape from the pocket too early, making bad reads and doing pretty dumb stuff.
"You just watch that stuff and it gives me so much more confidence that I can be so much better next year. There's so much to learn from. It's just good to be with the coaches and see what they see and talk over things after being a couple months removed from the season."
All but four players are participating in the voluntary program that began last week. Strength and conditioning coach Tom Kanavy said it's the best start to an offseason program he's had since he came to the NFL in 1995.
"It's been really good and I think it's obviously a testament to the young guys," linebacker Chad Greenway said. "We obviously have gone really young, I'd say, in the last couple years just with the change. Obviously, it's a testament to those guys wanting to be in here, be hungry and do the right thing."
Same deal
Initial discussions with new coordinator Alan Williams haven't yielded any indications the Vikings defense will undergo significant schematic changes, Greenway said.
Frazier hired Williams in January to replace Fred Pagac, who was demoted to his old role as linebackers coach after a season in which the Vikings finished 21st in total defense -- down from No. 8 in 2010 and their worst ranking in six years.
"We just had so many fundamental errors in what we do within our scheme," Greenway said. "Little things here or there, guys getting out of their gap, guys playing something different, miscommunication. There are more issues than just that, but you start with that and you work into the bigger issues."
Pagac will work this season alongside Mike Singletary, who was sole linebackers coach last season and also serves as assistant to the head coach. But Greenway said he expects Pagac to be in the lead role.
"He's going to be the one that has, I'm guessing, final say on what's going on schematically," Greenway said. "But they are on the same page. They are in this together, to get us better, and we're lucky to have both of them."
Health watch
Halfback Toby Gerhart said he never really considered having surgery on the medial collateral ligament he tore in the Jan. 1 season finale.
"They wanted to give it a month to six weeks to heal and see how it went from there," Gerhart said. "It healed down nicely, bound down nicely, and really no pain, so there's no reason to go in there yet."
Linebacker Jasper Brinkley, who missed all of last season following hip surgery, said he is "back totally, 100 percent. Ready to go. Any drill that Coach may think of, I can do it. I can do it to the best ability of anybody. If Chad can do it, I can do it."


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Mark Muro
China as Consumer?
September 29, 2009
There's a growing consensus that the U.S. needs to export more, and import less. The basic argument here is that huge recent imbalances between the consumption-mad U.S. on the one side and exporting China, Japan, Germany, and the Persian Gulf on the other can't go on and that we need to "rebalance" the global economy. And it sounds good, especially when Larry Summers says it. The only problem is, it's not clear to whom we would do all this new exporting.
Climate Calculus: Price + Innovation = Transformation
September 29, 2009
Alright, here we go on the climate front. After nearly a year of secretive discussions, Sens. Barbara Boxer (D-CA) and John Kerry (D-MA) will release global warming legislation Wednesday intended as a "starting point" for Senate negotiations that they hope will lead to an eventual conference with the House. That's good. Congress needs to get back to work on climate.
The Case for Clusters
September 22, 2009
President Obama gave a good speech yesterday in Troy, N.Y.
Obama's Innovation Speech
September 21, 2009
President Obama spoke today at Hudson Valley Community College in Troy, N.Y.
September 17, 2009
So it looks like the housing sector will soon start contributing--a little, in some places--to the economic recovery after contributing mightily to national breakdown. According to the Census Bureau, privately owned housing starts in August rose 1.5 percent above July levels to a seasonally adjusted annual rate of 589,000, which represents the fastest building pace since last November.
Making Sense with David Byrne
September 16, 2009
Some of us here at The Avenue are always poking our heads into each other's offices and referencing great "metro" songs, ranging from the obligatory anti-sprawl anthem "My City Was Gone" by the Pretenders to PJ Harvey's romantic "You Said Something" to Art Brut's witty defense of public transportation in "The Passenger." Always choice, despite their vintage, are songs by Talking Heads. David Byrne, the band's lead songwriter, embraced space and geography in many songs with scales ranging from neighborhood, to municipal, to metropolitan, to the super-regional and national.
Innovation: The Way Forward?
September 14, 2009
With speeches by White House economic advisor Larry Summers on Friday and President Obama today on Wall Street, the Obama administration is moving from triage as the chief aim of economic policy to recovery. Which is good: The job picture remains dismal, and many economists now assume any recovery will feature weak hiring and strong productivity growth as it did from 2001 to 2003. No wonder a lot of people are asking: From where will the next round of high-quality growth come? Which brings me to my answer: The next round of high-wage growth will come from metropolitan areas.
Taking the Fun out of Las Vegas
September 08, 2009
Wish you were here! Today, I'm in sunny Las Vegas to help roll out an interesting new Brookings initiative and realizing I'm residing at ground zero of America's current economic quandary. No large U.S. Metro has suffered greater house price declines in the last year. No large metro has a higher concentration of foreclosures. Gross metropolitan product has declined by 3 percent since its 2007 peak.
Biden Gets Real
September 03, 2009
There was a lot of standard defense of Team Obama stimulus policy in Vice President Biden's speech on the recovery act here at Brookings today.
Implementing ARRA--Another Way to Gauge Stimulus Success
August 31, 2009
With the President Obama's $787 billion stimulus package (aka, the American Recovery and Reinvestment Act or ARRA) six months old now, it's fair to ask like everybody else is: How's it working? One way to decide is to simply count the jobs created and jobs preserved. And on that front the commentariat has been quick to pronounce.