By MARILYNN MARCHIONE, AP Medical Writer

CHICAGO - Leading doctors urged a return to older, tried-and-true treatments for high cholesterol after hearing full results Sunday of a failed trial of Vytorin.

Millions of Americans already take the drug or one of its components, Zetia. But doctors were stunned to learn that Vytorin failed to improve heart disease even though it worked as intended to reduce three key risk factors.

“People need to turn back to statins,” said Yale University cardiologist Dr. Harlan Krumholz, referring to Lipitor, Crestor and other widely used brands. “We know that statins are good drugs. We know that they reduce risks.”

The study was closely watched because Zetia and Vytorin have racked up $5 billion in sales despite limited proof of benefit. Two Congressional panels launched probes into why it took drugmakers nearly two years after the study’s completion to release results.

Results were presented at an American College of Cardiology conference in Chicago Sunday and published on the Internet by the New England Journal of Medicine.

Doctors have long focused on lowering LDL or bad cholesterol as a way to prevent heart disease. Statins like Merck & Co.’s Zocor, which recently came out in generic form, do this, as do niacin, fibrates and other medicines.

Vytorin, which came out in 2004, combines Zocor with Schering-Plough Corp.’s Zetia, which went on sale in 2002 and attacks cholesterol in a different way.

The study tested whether Vytorin was better than Zocor alone at limiting plaque buildup in the arteries of 720 people with super high cholesterol because of a gene disorder.

The results show the drug had “no result — zilch. In no subgroup, in no segment, was there any added benefit” for reducing plaque, said Dr. John Kastelein, the Dutch scientist who led the study.

That happened even though Vytorin dramatically lowered LDL, fats in the blood called triglycerides and a measure of artery inflammation — CRP.

Some doctors noted that hormone pills for menopausal women and torcetrapib, a promising cholesterol drug Pfizer Inc. recently abandoned, also lowered cholesterol but were found in big studies to raise heart risks, not lower them.

Another ominous sign was the decision Friday by other researchers to expand enrollment in a more pivotal study of Vytorin to 18,000 people because early results suggest it will be harder than anticipated to see if it is any better than Zocor alone.

“It will be 2012 — ten years after the drug was introduced — before we know the answer,” said Dr. Steven Nissen, a Cleveland Clinic cardiologist who has no role in the studies and has criticized the drugmakers over the one reported Sunday.

Dr. Robert Spiegel, chief medical officer for Schering-Plough, said the study was done “with the highest integrity” and that doctors can believe the results “because of the time we took to make sure the data are right.”

“We were disappointed that it was not a very balanced panel discussion” by the heart doctors who urged their peers to focus on more established treatments.

However, Kastelein said the data were far more consistent than anticipated and ample to show that the drug simply did not work.

“A lot of us thought that there would be some glimmer of benefit,” said Dr. Roger Blumenthal, a Johns Hopkins University cardiologist and spokesman for the American Heart Association.

Many doctors have prescribed Vytorin without trying older, proven medications first, as guidelines advise. The key message from the study is “don’t do that,” Blumenthal said.

No one should ever stop any heart drug without talking with their doctors, heart specialists stressed.

However, doctors “should be thinking twice,” said Duke University cardiologist Dr. Robert Califf. He takes the drug himself because he cannot tolerate the high dose of statins he otherwise would need.

Dr. James Stein, director of preventive cardiology at the University of Wisconsin-Madison, said many doctors prescribe Zetia and Vytorin because they seem to be safe ways to get cholesterol down quickly, without annoying side effects like flushing that some other medicines carry.

Stein, who has consulted for Schering-Plough, said that after six years on the market, it would have been good to see better results on a drug so many doctors believed would help, “but the reason we do research is so we don’t have to rely on our ‘beliefs’ — we can rely on data.”

The New England Journal also published a report showing that Vytorin and Zetia’s use soared in the United States amid a $200 million advertising blitz. In Canada, where marketing drugs directly to consumers is not allowed, sales were four times lower.

Merck is based in Whitehouse Station, N.J.; Schering-Plough, in Kenilworth, N.J.

In addition to the two Congressional committee probes, New York State Attorney General Andrew Cuomo subpoenaed the companies in a similar probe in January.

“While these corporations profited, Americans were left in the dark,” Cuomo said in a written statement Sunday. “The millions who take this drug, taxpayers who subsidize its use through the Medicaid and Medicare programs, and Merck and Schering-Plough’s investors deserve to know why it took so long for the results to be made public. This new information underscores our concerns and advances our investigation, which we will pursue aggressively.”

By ARON HELLER, Associated Press Writer
JERUSALEM - A mathematical puzzle that baffled the top minds in the esoteric field of symbolic dynamics for nearly four decades has been cracked — by a 63-year-old immigrant who once had to work as a security guard.
 
Avraham Trahtman, a mathematician who also toiled as a laborer after moving to Israel from Russia, succeeded where dozens failed, solving the elusive “Road Coloring Problem.”

The conjecture essentially assumed it’s possible to create a “universal map” that can direct people to arrive at a certain destination, at the same time, regardless of starting point. Experts say the proposition could have real-life applications in mapping and computer science.

The “Road Coloring Problem” was first posed in 1970 by Benjamin Weiss, an Israeli-American mathematician, and a colleague, Roy Adler, who worked at IBM at the time.

For eight years, Weiss tried to prove his theory. Over the next 30 years, some 100 other scientists attempted as well. All failed, until Trahtman came along and, in eight short pages, jotted the solution down in pencil last year.

“The solution is not that complicated. It’s hard, but it is not that complicated,” Trahtman said in heavily accented Hebrew. “Some people think they need to be complicated. I think they need to be nice and simple.”

Weiss said it gave him great joy to see someone solve his problem.

Stuart Margolis, a mathematician who recruited Trahtman to teach at Bar Ilan University near Tel Aviv, called the solution one of the “beautiful results.” But he said what makes the result especially remarkable is Trahtman’s age and background.

“Math is usually a younger person’s game, like music and the arts,” Margolis said. “Usually you do your better work in your mid 20s and early 30s. He certainly came up with a good one at age 63.”

Adding to the excitement is Trahtman’s personal triumph in finally finding work as a mathematician after immigrating from Russia. “The first time I met him he was wearing a night watchman’s uniform,” Margolis said.

Originally from Yekaterinburg, Russia, Trahtman was an accomplished mathematician when he came to Israel in 1992, at age 48. But like many immigrants in the wave that followed the breakup of the Soviet Union, he struggled to find work in the Jewish state and was forced into stints working maintenance and security before landing a teaching position at Bar Ilan in 1995.

The soft-spoken Trahtman declined to talk about his odyssey, calling that the “old days.” He said he felt “lucky” to be recognized for his solution, and played down the achievement as a “matter for mathematicians,” saying it hasn’t changed him a bit.

The puzzle tackled by Trahtman wasn’t the longest-standing open problem to be solved recently. In 1994, British mathematician Andrew Wiles solved Fermat’s last theorem, which had been open for more than 300 years.

Trahtman’s solution is available on the Internet and is to be published soon in the Israel Journal of Mathematics.

Joel Friedman, a math professor at the University of British Columbia, said probably everyone in the field of symbolic dynamics had tried to solve the problem at some point, including himself. He said people in the related disciplines of graph theory, discrete math and theoretical computer science also tried.

“The solution to this problem has definitely generated excitement in the mathematical community,” he said in an e-mail.

Margolis said the solution could have many applications.

“Say you’ve lost an e-mail and you want to get it back — it would be guaranteed,” he said. “Let’s say you are lost in a town you have never been in before and you have to get to a friend’s house and there are no street signs — the directions will work no matter what.”

By MADLEN READ, AP Business Writer
NEW YORK - Wall Street fell in temperamental trading Monday as investors grappled with news of JPMorgan Chase & Co. buying the stricken Bear Stearns & Co. in a deal backed by the government. The Dow Jones industrials, down nearly 200 points in the early going, fluctuated into positive territory and then pulled back again.
A buyout of Bear Stearns was certainly more appealing than the alternative: letting the investment bank collapse and causing huge losses for anyone linked to it.

And some unprecedented moves by the Federal Reserve gave the market a bit of solace on what many predicted would be a day of precipitous losses in the stock market.

Besides supporting the buyout, the Fed lowered the rate it charges to loan directly to banks by a quarter-point on Sunday night — two days before its scheduled meeting Tuesday. The central bank also set up a lending option for firms, including many non-bank financial services firms, to secure short-term loans for a broad range of collateral.

“This removes the risk of further slides for these companies, the risk that a Bear Stearns incident would happen again,” said Robert Pavlik, portfolio manager at Oaktree Asset Management.

The Fed appears to be pledging to do everything in its power to keep the credit crisis from destroying the financial industry and the economy. Policy makers at the central bank are expected to reduce the target fed funds rate — the rate banks charge each other for overnight loans — by at least a half-point on Tuesday, and perhaps even a full point.

Still, the market remained extremely volatile, and a steeper drop Monday was still quite possible. The sale of Bear Stearns — and the fact that JPMorgan valued the fifth-largest Wall Street investment bank at a minuscule $2 a share, or $236 million — stirred fear among investors worldwide about other banks’ exposure to the troubled credit markets.

“You’re going to have some very weak players pushed out of business,” said Joseph V. Battipaglia, chief investment officer at Ryan Beck & Co. He said JPMorgan’s buy of Bear Stearns and Bank of America Corp.’s acquisition of mortgage lender Countrywide Financial Corp. are probably not the only rescues the industry will witness during this credit crisis.

The Dow fell 76.04, or 0.64 percent, to 11,875.05, after briefly venturing into positive territory.

Broader indexes also fell in choppy trading. The Standard & Poor’s 500 index fell 17.39, or 1.35 percent, to 1,270.75, while the Nasdaq composite index fell 34.22, or 1.55 percent, to 2,178.27.

JPMorgan, one of the Dow components, rose $3.55, or 9.7 percent, to $40.09. The Fed essentially guaranteed JPMorgan that it would backstop any risk involved in taking over the 85-year-old Bear Stearns, which has 14,000 workers worldwide.

Bear Stearns shares fell 86 percent to $4.20 — still above the buyout price, implying that some shareholders believe the deal terms might change. About one-third of Bear Stearns stock is held by its employees.

Bond prices rose as stocks fell. The yield on the benchmark 10-year Treasury note, which moves opposite its price, fell to 3.34 percent from 3.44 percent late Friday.

The dollar sank to a record low against the euro and hit a 12 1/2 year low against the yen, while gold prices surged to another record high.

Light, sweet crude dropped $2.47 to $107.74 per barrel on the New York Mercantile Exchange, after rising to nearly $112 a barrel in premarket trading.

The pain for investors in Bear Stearns, which succumbed to losing bets on souring mortgages for borrowers with poor credit, will be sizable. JPMorgan is buying Bear, including its midtown Manhattan headquarters, for about 1 percent of the investment bank’s worth little more than two weeks ago. Bear Stearns’ buyout arrives after a short-term bailout Friday that JPMorgan led and that the Fed backed.

The market’s concern wasn’t limited to the Bear sale. DBS Group Holdings Ltd., a large bank based in Singapore, instructed traders via e-mail Monday to disregard an earlier e-mail barring new transactions with Lehman Brothers Holdings Inc., according to Dow Jones Newswires. Earlier Monday, DBS emailed traders and said not to engage in new transactions with Lehman or Bear, according to two people familiar with the situation, Dow Jones reported.

Lehman fell $9.41, or 24 percent, to $29.85.

This week, Lehman and other major investment banks are slated to report quarterly results. Investors will likely be focusing on comments from the companies for insights about their financial well-being.

While investors were focused on the financial sector, fresh economic news offered little solace. The Fed said output at the country’s factories, mines and utilities fell by 0.5 percent in February, the biggest decline last October. Many analysts had been expecting a slight increase of one-tenth of one percent.

The Commerce Department also said Monday the broadest measure of foreign trade fell slightly in 2007 as stronger growth in U.S. exports helped make up for a spiking foreign oil bill. The deficit in the current account, which covers not only goods and services but also investment flows between the United States and other countries, dropped by 9 percent last year to $738.6 billion.

Declining issues outnumbered advancers by 5 to 1 on the New York Stock Exchange, where volume came to 619.9 million shares.

The Russell 2000 index of smaller companies fell 10.65, or 1.61 percent, to 652.25.

Overseas, Japan’s Nikkei stock average fell 3.71 percent, while Hong Kong’s Hang Seng index fell 5.18 percent. In afternoon trading, Britain’s FTSE 100 fell 2.32 percent, Germany’s DAX index dropped 3.29 percent, and France’s CAC-40 lost 2.52 percent.

By Nancy A. Youssef, McClatchy Newspapers
WASHINGTON — When U.S. forces crossed the Kuwaiti border into Iraq in the pre-dawn hours of March 20, 2003 , the military set out to shock and awe the Middle East with the swiftest transformation the region had ever seen.
Five years and hundreds of billions of dollars later, it’s the U.S. military that’s been transformed. The efficient, tech-savvy Army , built, armed and trained to fight conventional wars against aggressor states, is now making deals with tribal sheiks and building its power on friendly conversations with civilians.

Instead of planning for quick, decisive battles against other nations, as it was five years ago, today’s American military is planning for protracted, nuanced conflicts with terrorist groups, insurgents, guerrillas, militias and other shadowy forces that seldom stand and fight.

The staples of American military doctrine that have developed since the Civil War — artillery, armor, air power, speed and overwhelming force— are of limited use against enemies who blend into civilian populations.

Five years after the U.S.-led invasion of Iraq , the military is being reconfigured to fight insurgencies, but its evolution has been an unplanned, improvised affair, a series of course corrections in the midst of the wars in Iraq and Afghanistan . Some changes have been simply last-ditch efforts to stop the violence against Iraqis and U.S. troops, and some say the changes impair the military’s ability to fight a conventional war against a “peer competitor.”

Divisions are dispersed into what the military calls a more modular Army so smaller units can be moved throughout Iraq . The military has rolled out new vehicles to thwart high-powered explosives. It’s set up new training centers and given captains and colonels far more leeway to lead at the local level, not simply follow a general’s orders.

Pentagon leaders call this the military of the future.

“Clearly the training now is almost exclusively focused on COIN (counterinsurgency) because that’s the fight we are in. And it will continue that way as long as the fight stays at the level that it is,” said Adm. Michael Mullen , chairman of the Joint Chiefs of Staff, in an interview with McClatchy .

In the last five years, the military has gained “speed, agility (and) flexibility that . . . we didn’t have as a much heavier force” a few years ago, Mullen said.

It’s a big departure from the transformation that then-Secretary of Defense Donald H. Rumsfeld promised in the months leading up to the war. Under his plan, the Army would be smaller and rely more on precision air attacks and the latest technology.

Indeed, the war in Iraq was supposed to last a few weeks. The U.S. would dispatch the Iraqi military, overthrow Saddam Hussein’s regime, install a new government led by Iraqi exiles and introduce freedom, democracy and a market economy.

Within days, however, the U.S. lost control. Looters took to the streets, and an insurgency took root. The U.S. installed an American occupation government and tried to secure a hostile nation rather than a grateful one.

Back then, there was little talk of counterinsurgency. But the new Army Field Manual puts counterinsurgency on a par with conventional war. “Winning battles and engagements is important but alone is not sufficient,” it states. “Shaping the civil situation is just as important to success.”

But while the Army has intellectually embraced counterinsurgency, it hasn’t said how it will build a force that can fight both conventional wars and counterinsurgency campaigns. How should it train its soldiers? What kind of enemy will the U.S. face? So far, military leaders cannot agree on those fundamental questions.

By adopting a new mode of warfare, “the Army is a python that has just swallowed a pig,” said a U.S. Army officer who spoke on the condition of anonymity in order to speak more candidly. “It’s not clear to me it understands how hard the digestion process is going to be.”

“The Army is going to have to build organizations optimized to do (post-combat) stability operations, and that’s not what this Army wants to do,” the officer added.

Lt. Col. John Nagl , who co-authored the U.S. military’s 2006 counterinsurgency manual with Gen. David Petraeus , now the top American military commander in Iraq , questions whether the Army is serious about counterinsurgency.

“The real question is: How does the Army react to the (new field manual)? Can the Army transform itself to be as effective as possible in future battles, which are going to look a lot like Iraq and Afghanistan ?” Nagl said in an interview with McClatchy .

Some think that Iraq is a temporary problem and that the U.S. shouldn’t engage in nation-building, as called for under counterinsurgency strategy.

Some think the Army isn’t prepared for both kinds of war. Pete Geren , the secretary of the Army , testified on Capitol Hill last month that as the Army steps up counterinsurgency training, it’s losing its conventional war skills.

“Our goal is full-spectrum readiness. And right now we’re— we’re not able to claim that,” Geren said. “We are not able to properly organize, train and equip for the rest of the spectrum of operations.”

Gen. George Casey , the Army chief of staff, has repeatedly warned that the Army is strained by having 160,000 troops in Iraq . Other Army leaders estimate that the U.S. must reduce its deployment to 12 combat brigades from the current 18 or find itself at the “breaking point.”

The war in Iraq has required some soldiers to serve multiple tours of up to 15 months and to remain in uniform longer than they signed up for. Before the war started, soldiers generally served six-month tours in combat zones.

Mullen acknowledged the friction between counterinsurgency and conventional warfare.

“I think that (tension) will be constructive, and actually with what we learned through counterinsurgency, potentially very creative tension as we move to the next several years to get back to a broader spectrum of training.”

The military’s embrace of counterinsurgency came only in the last 18 months as soldiers noted measurable security improvements in Iraq . In the early years of the war, only a handful of military commanders spoke of the importance of economic development, respecting civilians and employing military might cautiously.

Back then, many ridiculed using “soft power” against what they considered a ruthless enemy. Soldiers said they were in Iraq to fight.

These days in Iraq , soldiers say they’re likely to spend the rest of their careers in places such as Iraq , reaching out to civilians and fighting major battles only occasionally. Instead of generals giving orders from behind the front lines, captains and colonels will be forced to adapt as they maneuver through local, tribal politics. And many soldiers say those mid-level leaders will base their decisions on their experiences in Iraq .

Sgt. John Pierce Senkarik , 25, of 1st Brigade, 4th Stryker Brigade Combat Team, is serving in Diyala province, and could be one of them. Senkarik, of Pensacola, Fla. , comes from a family imbued with military history, and he once thought he’d fight the same kind of battles his forebears did. But since he signed up, he said, he’s seen a transformation within the Army .

Senkarik, who’s serving his second tour in Iraq , said he plans to stay in the military so the Army can capitalize on his experiences there.

“The Army is filled with junior leaders and middle-level leaders who have a vast amount of combat experience in counterinsurgency, in urban combat,” he said. Mid-level officers will lead and be “responsible for the up-and-coming Army .”

( Steve Lannen of the Lexington Herald-Leader contributed from Diyala province, Iraq .)

HONOLULU - Some investigative work by a New York couple has led to return of a McKinley High School ring 33 years after it was lost on Waikiki. McKinley alumnus Bernard Yuen had given his 1973 class ring to a girlfriend in 1975.

The girl had left the black onyx ring on a beach towel, but then forgot about it when she picked up the towel.

Brian and Jodi Sheley of Adams Center, N.Y., got the ring from an uncle from Hawaii years ago and used the Internet to track down Yuen, whose initials BJKY were inscribed on the ring. They speculate it was found by someone with a metal detector.

The Sheleys, who told their story to WNYF-TV in New York on Valentine’s Day, used the Internet to find McKinley and the 1973 class president who was a friend of Yuen and recognized the initials.

The girlfriend has moved to California, and Yuen is married to someone else.

But he’s got the ring back.