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9:20am 04/07/05
Pfizer asked by FDA to take Bextra off the market (PFE) By Tomi Kilgore
NEW YORK (MarketWatch) -- The U.S. Food and Drug Administration has asked Pfizer (PFE) to withdraw its arthritis pain reliever Bextra from the market, due to an unfavorable benefit vs. risk profile. The FDA also asked the drugmaker to add a warning on its painkiller Celebrex about an increased risk of cardiovascular and gastrointestinal events. Pfizer's stock, a component of the Dow industrials, fell 4.2% to $25.73 in Instinet pre-open trading. All other makers of non-steroidal anti-inflammatory drugs were asked to revise their labels to add the same warning.
Another DNAP candidate!
Hey Where'd all the bashers go????
GO DNAP Help!!!!!!
Tony indicated that he needed shareholder approval in order to issue the additional shares. Therefore, he would need to make sure that all shares are listed by their owners for voting purposes.
It would appear that we have found our market bottom at .006 as there are no sells at .0059.
My estimation is that there will be a significant reversal next Tuesday when the FDA mentions DNA Print as the Gold standard in pharmacogenetics.
Groan! — FDA Again Delays Release of Pharmacogenomic Data Submissions Guidance
By Chris Womack, Pharmacogenomics Reporter editor
NEW YORK, March 17 (GenomeWeb News) - The US Food and Drug Administration has again delayed the release of its Guidance for Industry on Pharmacogenomic Data Submissions, this time to March 22, GenomeWeb News has learned.
"They were originally scheduled for release on Friday, and now that's been bumped back to Tuesday," a spokesperson for the FDA Center for Drug Evaluation and Research told GenomeWeb News. The spokesperson was careful to add that the schedule may be revised yet again.
In the most recent update, GenomeWeb News reported the announcement by Larry Lesko, CDER director of the office of clinical pharmacology and biopharmaceutics, that the guidance would be released on Friday. Lesko made the comment at last week's Drug Information Association conference in Lisbon, Portugal.
The long-awaited document will appear on a special FDA website, Federico Goodsaid, an official at the agency's Office of Clinical Pharmacology and Biopharmaceutics, said during a lecture at the Society of Toxicology meeting in New Orleans last week.
During his presentation, Goodsaid said the FDA will release the final guidance "within a week or two."
The document, whose approval has been delayed numerous times since it was released as a draft in November 2003, may serve to encourage drug makers to use pharmacogenomics technologies in their drug-discovery efforts, and submit some of their findings as a way to help the FDA broaden its knowledge of the technologies.
DNA is Genetech..not DNAP
Is the Boom...an explosion or an implosion?
Let's see a 3 for 1 forward stick split or a 1 for 3 reverse split. Boom or bust
FDA Will Release Pharmacogenomics Guidance on Friday, Agency Officials Say
By a GenomeWeb staff reporter
NEW YORK, March 14 (GenomeWeb News) - The US Food and Drug Administration will release its Guidance for Industry on Pharmacogenomic Data Submissions on Friday, according to two agency officials.
Larry Lesko, director of the office of clinical pharmacology and biopharmaceutics at the FDA's Center for Drug Evaluation and Research, announced the day during a presentation at a Drug Information Association conference in Lisbon, Portugal, last week. Lesko and Felix Frueh, CDER's associate director for genomics, both confirmed the date through an FDA spokesperson last Friday.
The long-awaited document will appear on a special website that the FDA will launch this week, Federico Goodsaid, an official at the agency's Office of Clinical Pharmacology and Biopharmaceutics, said during a lecture at the Society of Toxicology meeting in New Orleans last week.
During his presentation, Goodsaid said the FDA will release the final guidance "within a week or two."
The document, whose approval has been delayed numerous times since it was released as a draft in November 2003, may serve to encourage drug makers to use pharmacogenomics technologies in their drug-discovery efforts, and submit some of their findings as a way to help the FDA broaden its knowledge of the technologies.
Looks like Biofrontra deal is off but Duchess financing is still possible
The door is open..
New FDA Genotyping Guidance Opens Door to AmpliChip Rivals
By Kirell Lakhman, GenomeWeb News editor
NEW YORK, March 11 (GenomeWeb News) - A recently released guidance issued by the US Food and Drug Administration will make it easier for Roche and Affymetrix rivals to win FDA clearance for tests that resemble the AmpliChip drug-metabolism diagnostic, GenomeWeb News has learned.
The document, entitled Class II Special Controls Guidance Document: Drug Metabolizing Enzyme Genotyping System, may help molecular diagnostic companies and their microarray partners more efficiently develop and submit their own array-based tests that help predict drug metabolism.
The Guidance is standard procedure, according to an FDA official. For a device that has no "predicate" product against which the FDA can draw a comparison --- as was the case for the AmpliChip when it was being reviewed by the FDA --- manufacturers are required to undergo a laborious pre-market approval process. This process "takes a long time and requires clinical trials," the FDA official said.
In the case of the AmpliChip and the resulting Class II guidance, which was released on the Center for Devices Radiological Health's web site on March 9, the document serves as a kind of roadmap for diagnostic companies wishing to market a product similar to the AmpliChip. In order for these companies to win FDA clearance for their products and begin marketing them as in vitro diagnostics like the AmpliChip, they will be required to "go by the [less stringent] 510(k) process and not have to do the pre-market approval," the FDA official said.
The document also means that Roche can go back to the FDA with a product similar to the AmpliChip and not have to go through the same approval process as it had originally, the official noted.
The FDA issues these guidances "to give people an idea of how they can assure safety and effectiveness, and what types of things the FDA will need to review" for their own 510(k) clearance, she said.
The official asked not to be named because FDA policy requires their employees to maintain anonymity when talking to the press.
As GenomeWeb News reported in January, the FDA cleared the second of two genes in Roche's AmpliChip CYP450 test, clearing the way for the device to be sold as an in vitro diagnostic in the United States.
The approval came three weeks after the FDA cleared the first half of the product. The AmpliChip, based on Affymetrix's Gene Chip technology, comprises two genes in the CYP450 family: 2D6 and 2C19.
As GenomeWeb News reported in December 2004, the FDA on Dec. 23 approved the 2D6 portion, but made no statement about the 2C19 gene.
The final approval means that physicians in the United States will be able to prescribe the test, which could help them decide dosages for drug families such as anti-depressants, anti-psychotics, anti-arrhythmics, beta-blockers, analgesic, anti-emetics, cancer drugs, anti-convulsants, proton pump inhibitors, benzodiazepines, and anti-malarials. (Pharmacogenomics Reporter, a GenomeWeb News publication, published an article in January that mentioned Roche's marketing strategy for the AmpliChip.)
The AmpliChip was approved for sale in the European Union in September.
"The use of this test is an important step forward in making personalized medicine a reality and has the potential to help physicians improve patient outcomes," Heino von Prondzynski, CEO of Roche Diagnostics, said in a statement in January.
According to Roche, multiple variations in the CYP2D6 gene can "result in poor, intermediate, extensive ("normal"), or ultra- rapid metabolism of CYP2D6-dependent drugs from a variety of classes," including anti-depressants, anti-psychotics, anti-arrhythmics, beta-blockers, analgesics, anti-emetics, and "some" anti-cancer drugs.
Variations in the CYP2C19 gene, meantime, "result in either normal or poor metabolism of CYP2C19-dependent drugs from a variety of classes, including anti-convulsants, proton pump inhibitors, benzodiazepines, and anti-malarials," the Swiss diagnostics giant said.
"Physicians can use the genetic information from this test to prevent harmful drug interactions and to assure drugs are used optimally, which in some cases will enable patients to avoid less effective or potentially harmful treatment choices," Lester Crawford, acting FDA commissioner, said in an agency statement in January.
The FDA said that the AmpliChip "is the first DNA microarray test to be cleared by the FDA and its clearance paves the way for similar microarray-based diagnostic tests to be developed in the future."
Affy's GeneChip System 3000Dx instrument, on which the AmpliChip CYP450 test is run, was cleared by the FDA on Dec. 23
and on the lighter side.....
A True Redneck from Grand County
To give you some background information, Rex, the author of this email, is in his mid 40's about 6'4and220 lbs. and contrary to this story, he is quite an intelligent person.
Dear Friends,
My wife is fond of saying that my last words on this earth will be something akin to "Well, I have out done myself once again." No doubt you will see this true story chronicled in a Life Time movie in the near future. Here goes.
Last weekend I spied something at the Pawnshop that tickled my fancy.(Note: Keep in mind that my "fancy" is easily tickled.) I bought something really cool for my wife. The occasion was ou 22nd anniversary and I was looking for a little something extra for my sweet girl.
What I came across was a 100,000-volt, pocket/purse-sized Tazer gun with a clip. For those of you who are not familiar with this product, it is a less-than-lethal stun gun with two metal prongs designed to incapacitate an assailant with a shock of high-voltage, low amperage electricity while you flee to safety. The effects are supposed to be short lived, with no long-term adverse affect on your assailant, but allowing you adequate time to retreat to safety. You simply jab the prongs into your 250 lb. tattooed assailant, push the button, and it will render him a slobbering, goggle-eyed, muscle-twitching, whimpering, pencil-neck geek. If you've never seen one of these things in action, then you're truly missing out--way too cool!
Long story short, I bought the device and brought it home. I loaded two AAA batteries in the darn thing and pushed the button. Nothing! I was so disappointed. Upon reading the directions (we don't need no stinkin' directions), I found much to my chagrin that this partic! ular model would not create an arch between the prongs. How disappointing, I do love fire for effect. I learned that if I pushed the button, however, and pressed it against a metal surface that I'd get the blue arch of electricity darting back and forth between the prongs that I was so looking forward to. I did so. Awesome!!! Sparks, a blue arch of electricity, and a loud pop!!!
Yipeeeeee. I'm easily amused, just for your information, but I have yet to explain to her what that burn spot is on the face of her microwave.
Okay, so I was home alone with this new toy, thinking to myself that it couldn't be all that bad with only two triple-a batteries, etc, etc. There I sat in my recliner, my dog looking on intently (trusting little soul), reading the directions (that would be me, not the dog) and thinking that I really needed to try this thing out on a flesh and blood target. I must admit I thought about zapping the dog for a fraction of a second and thought better of it. She is such a sweet pup, after all. But, if I was going to g! ive this thing to my wife to protect herself against a mugger, I did want some assurance that it would work as advertised. Am I wrong? Was I wrong to think that? Seemed reasonable to me at the time. So, there I sat in a pair of shorts and a tank top with my reading glasses perched delicately on the bridge of my nose, directions in one hand, Tazer in another. The directions said that a one-second burst would shock and disorient your assailant; a two-second burst was supposed to cause muscle spasms and a loss of bodily control; a three-second burst would purportedly make your assailant flop on the ground like a fish out of water.
All the while I'm looking at this little device (measuring about 5" long, less than 3/4 inch in circumference, pretty cute really, and loaded with two itsy, bitsy AAA batteries) thinking to myself, "no friggin' way!" Friggin' way - trust me, but I'm getting ahead of myself.
What happened next is almost beyond description, but I'll do ! my best. Those of you who know me well have got a pretty good idea of wh at followed. I'm sitting there alone, the dog looking on with her head cocked to one side as to say, "don't do it buddy," reasoning that a one-second burst from such a tiny lil' ole thing couldn't hurt all that bad (sound, rational thinking under the circumstances, wouldn't you agree?). I decided to give myself a one-second burst just for the hell of it (Note: You know, a bad decision is like hindsight-- always twenty-twenty. It is so obvious that it was a bad decision after the fact, even though it seemed so right at the time. Don't ya hate that?)
I touched the prongs to my naked thigh, pushed the button, and HOLY *********!!!! I'm pretty sure that Jessie Ventura ran in through the front door, picked me up out of that recliner, then body slammed me on the carpet over and over again. I vaguely recall waking up on my side in the fetal position, nipples on fire, testicles nowhere to be found, soaking wet, with my left arm tucked under my body in the oddest position. The dog was standing over me making sounds I had never heard before, licking my face, undoubtedly thinking to herself, "do it again, do it again!"
(Note: If you ever feel compelled to mug yourself with a Tazer, one note of caution. There is no such thing as a one-second burst when you zap yourself. You're not going to let go of that thing until it is dislodged from your hand by a violent thrashing about on the floor. Then, if you're lucky, you won't dislodge one of the prongs 1/4" deep in your thigh like yours truly.)
SON-OF-A-***** that hurt! A minute or so later (I can't be sure, as time was a relative thing at this point), I collected my wits (what little I had left), sat up and surveyed the landscape. My reading glasses were on the mantel of the fireplace. How did they get there??? My triceps, right thigh and both pecs were still twitching. My face felt like it had been shot up with Novocain, as my bottom lip weighed 88 lbs. give or take an ounce or two! By the way, has anyone seen my testicles? I think t hey ran away. I'm offering a reward. Miss 'em . sure would like to get'em back.
Jim Campbell
P.O. Box 84
Hot Sulphur Springs, CO 80451
970-627-8727
Decliners led advancing stocks 4:1 just another bad day at the office....keep the faith
Easy... is being a spook a paid position or just for fun??
Where's GO DNAP when we really need him?????
If Orchid is a distributer of DNAP testing kits, then the following would be indicative of the distribution network that DNAP is tapping into.
Orchid Cellmark
Orchid Cellmark, a leader in private forensic DNA analysis since 1987, is known for the consistent high quality of its work and its expert staff of forensic scientists. With an international network of forensic testing laboratories in the U.S. and U.K., Orchid Cellmark is the largest private DNA forensic testing service provider in the world. Orchid Cellmark provides a full range of high quality, customized forensic DNA testing services, including identification of victims of accidents and disasters, criminal casework analysis and expert testimony, convicted offender DNA databasing, no-suspect casework for government law enforcement laboratories, and DNA testing and consultative services for the defense bar as well as for the prosecution. Orchid Cellmark's services have been selected by major police departments in the U.S., such New York City, Chicago, Phoenix, and Houston, Texas, as well as in the U.K., including London's Metropolitan Police Force, which is commonly referred to Scotland Yard. Name a high profile criminal investigation, and there is a good chance that Orchid Cellmark experts palyed a role, having conducted DNA testing for such notable cases as O.J. Simpson, Jon Benet Ramsey, Danielle Van Dam, the Unabomber, and the Green River murderer.
All three U.S. Orchid Cellmark facilities have received the prestigious forensic DNA Laboratory ASCLD/LAB accreditation, a designation which only a small number of private DNA laboratories has been awarded. Its Nashville, Tenesee facility was one of the first full-service private forensic DNA laboratories to receive the ISO 17025 accreditation in the U.S. Orchid Cellmark also holds many additional accreditations and certifications in the U.S. and the U.K.
Orchid Cellmark uses a variety of genetic analysis methods for its forensic DNA studies and is a leader in developing improved technologies for genetic analysis. Recently, Orchid Cellmark furthered its reputation as an innovator by collaborating with the New York City Medical Examiner's Office to conduct SNP-based genotyping tests to help identify the large number of 9/11 World Trade Center victims for whom other methods have failed. Orchid Cellmark is also exploring the use of SNPs in other difficult cases involving degraded samples.
As the value in DNA testing in solving crimes is increasingly recognized, federal and state agencies are allocating greater resources to support wider use of identification through DNA. We believe that Orchid Cellmark is well positioned to benefit from what we expect to be robust growth in the market for criminal forensics. In 2003, Orchid Cellmark launched DNA Express™, a premium service to help local law enforcement agencies analyze backlogs of DNA evidence from unsolved crimes. DNA Express provides forensic DNA analyses in five business days as opposed to the standard four to five weeks.
DNA evidence has been used to link suspects to crimes for years. But could it soon be used to help describe suspects? Could our blood be used to tell police what we look like. Seven's Patrick Fraser takes a look into the future of crime solving in his special assignment report.
WSVN -- Samantha Steinberg has a rare talent...
Samantha Steinberg from Miami-Dade Police: "How would you describe his complexion?"
The Miami-Dade Police sketch artist can turn someone's memories of a criminal...Into an image.
Images that can help nab dangerous suspects.
Samantha Steinberg: "We had a serial rapist in Kendall back in 2000."
Samantha drew a sketch that was so realistic -- an officer spotted him while investigating a burglary.
Samantha Steinberg: "One of the responding officers from the Kendall district recognized him as being similar to the composite of the Kendall serial rapist."
Thanks to the sketch, Jose Antonio Castro was arrested and he's still awaiting trial. But sometimes it takes more than a sketch to catch a crook.
The parents of Carrie Lynn Yoder got the horrible news...she had been murdered.
Carrie's Mother Lynda Yoder: "The only thing he left behind was DNA there was no fingerprints."
Carrie was a victim of a serial killer stalking young women in Louisiana. FBI profilers concluded that police should look for a white man -- A witness even agreed.
Lynda Yoder: "There was an eyewitness to a white man in a white truck. And, they were focusing on a white person."
The police had the suspects DNA -- But no suspect.
Lynda Yoder: "I was extremely frustrated."
Then investigators sent the killer's DNA to this Florida company, A company called DNA Print Genomics which can use DNA in an incredible way.
Dr. Tony Frudakis DNA Print Genamics: "This gives you information. Scientific information about what a person might look like."
When the company got through with their test, it literally turned the manhunt around for Louisiana investigators. Instead of a white suspect, DNA markers pointed to an African American..
A month later, Eric Todd Lee was in custody.
Dr. Frudakis: "The Louisiana serial killer would still be walking around today we believe if it weren't for the millions of dollars we've invested in this research."
The conviction was a giant step forward for law enforcement, and for the founder of DNA Print Generics. A step that he suspects only a private company could have made.
"Most government funded institutions wouldn't dream of developing a test like this. Frankly, because it's politically incorrect."
Politically incorrect critics say because it will lead to more racial profiling.
Howard Simon from the ACLU: "We had a serial rapist in the city of Miami that was thought to be an Hispanic male."
Simon says the advanced DNA testing will convince police to target one race based on the test results, and he thinks that is dangerous.
Howard Simon: "You can't say gee, a white man committed this crime so now every white man is a suspect. You can't do that."
But backers of the test say what you can do is give police a better idea of who to look for...To help catch the criminal more quickly.
You'll have tests developed for features such as body mass index, hair color, whether the earlobes are connected for instance and gross facial morphology such as the width and length of the face which are largely determined by genetics.
And even the ACLU admits, if the science is used properly -- it can be a powerful police too.
"Advances in technology help law enforcement. That of course is a good thing."
In carries case it was a good thing. It got a murdered off the street.
Carrie's Mom: "He'd still be out there Killing."
A great advance in science, as long as the body of evidence helps police catch the right body, because when a killer is loose, anyone's daughter could be the next target.
And that body of evidence is enough to show any and all new technology should be here to stay.
A number of police agencies around the country have sought out the Tampa lab for DNA racial tests. But so far, no police agency here in South Florida has been using it.
I am curious to the fact that the DNA Print website has not been updated to remove the Biofrontera deal language and has not been showing any new 'news' as of late.
Is it that there is no news or the web site is sadly outdated and neglected? Not a very promising picture.
Interesting? I wonder......
Perlegen Nabs $74M in Private Stock Placement; Cash to Flesh Out Drug Pipeline
By a GenomeWeb News reporter
NEW YORK, Feb. 28 (GenomeWeb News) - Perlegen Sciences has closed $74 million in a private placement of its Series D Preferred Stock with new and existing investors, the company said today.
The company will use the equity financing "to continue in-licensing and developing a ... pipeline of late-stage drugs, exploiting Perlegen's ability to target the right drugs to the right patients," Robert Middlebrook, chief corporate development officer of Perlegen, said in a statement.
CSK Venture Capital led the financing, followed by new investors Brookside Capital, an affiliate of Bain Capital; Mizuho Securities; Glynn Capital Management; Cape Securities; and "several other" USand European institutional investors.
Previous investors also participating in the financing included Affymetrix, Alex Zaffaroni, Maverick Capital, Lombard Odier Darier Hentsch & Cie, Zesiger Capital, Sano Ventures, BSI SA, MPM BioEquities, SB Life Sciences, Unilever Ventures, Biofrontier Partners, Private Life Biomed, and CMEA Ventures.
Gene Codes Signs $1.6M Contract to Identify Tsunami Victim Remains
By a GenomeWeb staff reporter
NEW YORK, Feb. 24 (GenomeWeb News) - The Thai government will pay Gene Codes $1.6 million for the company to use its DNA-matching software to identify human remains left in the wake of last year's Indian Ocean tsunami.
Gene Codes will use its M-FISys software to match apparently non-Thai DNA profiles sent to the company by the Beijing Genomics Institute at the Chinese Academy of Sciences, which receives tissue samples of all tsunami victims in Thailand, said Howard Cash, president of Gene Codes.
The company will match the profiles with identification data generated from pre-tsunami victim samples and family-member samples obtained from victims' families through national governments, Cash said.
The Thai Police Forensic Institute victim identification center in Phuket, Thailand, currently holds 1,552 bodies, while the Central Institute of Forensic Science is processing 1,538 at two locations, according to a Feb. 21 article in the Bangkok Post.
Gene Codes previously identified the remains of World Trade Center-disaster victims in New York following the Sept. 11, 2001 terrorist attacks.
ASFT, Inc. is a registered "Women Owned" company which enables it to be a prime candidate to sell and bid on Government contracts.
....however if you read the far right column of the filing the "beneficial ownership" is ASFT, Inc.
It would appear that Vikki Cook is representing ASFT, Inc. a large Government logistics group. i.e. distribution channel
Market capitalization perhaps
DNAP at 11,000,000 shares!!!! Sound like the finance department is working overtime.
Forgive my asking..but what is the connection between DNAPrint and DNApheomics ??
Skull found in serial killer investigation
By Jan Dennis
Associated Press
Advertisement
PEORIA -- More human remains, including part of a skull, were unearthed Friday as searchers continued digging at sites where prosecutors say an alleged serial killer told them he disposed of four of his eight victims, authorities said.
Peoria County State's Attorney Kevin Lyons said human remains had been found at several locations, including "sizeable bones" and skull parts found near the suspect's grandmother's home in Bellevue, just west of Peoria.
Authorities said digging would continue through the weekend at about a half-dozen sites pointed out by Larry Bright, a 38-year-old former concrete worker who was charged Thursday with murdering one woman and who prosecutors say confessed to killing seven others as well.
During his first court appearance in the September slaying of Linda Kay Neal, Bright told the judge: "I just would like to plead guilty, sir." The judge rejected it and assigned the public defender's office to represent him.
The office had not yet appointed an attorney who could comment on the case Friday.
The bodies of four of the victims had turned up along rural roads in neighboring Peoria and Tazewell counties since the summer of 2003. But the four others, all reported missing in the past year, had never been found.
Prosecutors now believe Bright burned those bodies in pits near the converted garage where he lived behind his mother's house in rural Peoria, then crushed the bones and disposed of the remains at various locations.
The burning likely destroyed all of the human tissue, but bone also contains DNA and can often withstand prolonged exposure to fire, said Mark Stolorow, executive director of Orchid Biosciences, the nation's largest private genetic testing lab.
Half of the 20,000 tissue and bone fragments recovered from the World Trade Center yielded samples for DNA testing, Stolorow said. Tests also identified two-thirds of 80 victims after the 1993 blaze at the Branch Davidian compound in Waco, Texas.
"There's a possibility some or all will be perfectly typeable, and a possibility that some or all won't be typeable at all. You can't predict without knowing the extent of the damage," said Stolorow, whose lab was among three that tested remains from the World Trade Center.
Water, humidity and other factors can also destroy DNA, he said. And prosecutors believe the remains of the women Bright is accused of killing had been dumped outdoors.
Human remains found during the Peoria killings investigation are being sent to an FBI lab for testing, and results could be available within a month, said Peoria County Chief Deputy Joe Needham.
Lyons said he would seek indictments in as many of the eight slayings as he could connect to Bright with evidence, and he expects a grand jury will issue indictments before Bright's next scheduled court appearance on Feb. 24.
Bright, who has been jailed since December on a separate charge, has been on suicide watch since videotaping a confession Wednesday, authorities said.
Lyons said Bright confessed in the deaths of eight of the 10 women whose deaths or disappearances led to the creation of a task force last fall to find and stop their killer. That task force will continue to investigate the two deaths that remain unaccounted for after Bright's confession, Needham said
OK Here's the big news as per todays WSJ Friday is a key day for naked short sellers to cover or become listed on the SEC's bad boy list. Although, the SHO reg. became effective 1/3/05 apparently tommorrow is "D" day.
Outstanding post!!!!
.0078 PPS The test of a true long. Hold on tight.....
Sounds like DNAPrint is ramping up their staff levels and getting ready for some serious business increases!!
There's always a glimmer of hope where the odds seemingly are stacked against a new science. I'm confident that the DNAPrint team will not take the pps issue lightly.
Can't be I just placed an order for 3000 at .0104 and it did not fill!!!
With the advent of the new SHO reg. effective 1/3/05 when would we anticipate the "squeeze" to have an impact on PPS?