'Entourage' crew to make leap to big-screen

LOS ANGELES (AP) — Vincent Chase and his entourage are jumping from the small screen to the big-screen.

Warner Bros. confirmed Wednesday that a film version of HBO's hit series "Entourage" is in the works.

Series creator Doug Ellin is writing and directing the film, which does not yet have a production start date or release date. The studio also has not finalized the cast.

"Entourage" ran for eight seasons and followed the Hollywood exploits of hot young actor Vince (Adrian Grenier) and his inner circle, including Kevin Connolly as his manager, Kevin Dillon as his half brother, Jerry Ferrara as an old neighborhood friend and Jeremy Piven as his slick super-agent.

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The Consumer: The Drug-Dose Gender Gap

Most sleeping pills are designed to knock you out for eight hours. When the Food and Drug Administration was evaluating a new short-acting pill for people to take when they wake up in the middle of the night, agency scientists wanted to know how much of the drug would still be in users’ systems come morning.

Blood tests uncovered a gender gap: Men metabolized the drug, Intermezzo, faster than women. Ultimately the F.D.A. approved a 3.5 milligram pill for men, and a 1.75 milligram pill for women.

The active ingredient in Intermezzo, zolpidem, is used in many other sleeping aids, including Ambien. But it wasn’t until earlier this month that the F.D.A. reduced doses of Ambien for women by half.

Sleeping pills are hardly the only medications that may have unexpected, even dangerous, effects in women. Studies have shown that women respond differently than men to many drugs, from aspirin to anesthesia. Researchers are only beginning to understand the scope of the issue, but many believe that as a result, women experience a disproportionate share of adverse, often more severe, side effects.

“This is not just about Ambien — that’s just the tip of the iceberg,” said Dr. Janine Clayton, director for the Office of Research on Women’s Health at the National Institutes of Health. “There are a lot of sex differences for a lot of drugs, some of which are well known and some that are not well recognized.”

Until 1993, women of childbearing age were routinely excluded from trials of new drugs. When the F.D.A. lifted the ban that year, agency researchers noted that because landmark studies on aspirin in heart disease and stroke had not included women, the scientific community was left “with doubts about whether aspirin was, in fact, effective in women for these indications.”

Because so many drugs were tested mostly or exclusively in men, scientists may know little of their effects on women until they reach the market. A Government Accountability Office study found that 8 of 10 drugs removed from the market from 1997 through 2000 posed greater health risks to women.

For example, Seldane, an antihistamine, and the gastrointestinal drug Propulsid both triggered a potentially fatal heart arrhythmia more often in women than in men. Many drugs still on the market cause this arrhythmia more often in women, including antibiotics, antipsychotics, anti-malarial drugs and cholesterol-lowering drugs, Dr. Clayton said. Women also tend to use more medications than men.

The sex differences cut both ways. Some drugs, like the high blood pressure drug Verapamil and the antibiotic erythromycin, appear to be more effective in women. On the other hand, women tend to wake up from anesthesia faster than men and are more likely to experience side effects from anesthetic drugs, according to the Society for Women’s Health Research.

Women also react differently to alcohol, tobacco and cocaine, studies have found.

It’s not just because women tend to be smaller than men. Women metabolize drugs differently because they have a higher percentage of body fat and experience hormonal fluctuations and the monthly menstrual cycle. “Some drugs are more water-based and like to hang out in the blood, and some like to hang out in the fat tissue,” said Wesley Lindsey, assistant professor of pharmacy practice at Auburn University, who is a co-author of a paper on sex-based differences in drug activity.

“If the drug is lipophilic” — attracted to fat cells — “it will move into those tissues and hang around for longer,” Dr. Lindsey added. “The body won’t clear it as quickly, and you’ll see effects longer.”

There are also sex differences in liver metabolism, kidney function and certain gastric enzymes. Oral contraceptives, menopause and post-menopausal hormone treatment further complicate the picture. Some studies suggest, for example, that when estrogen levels are low, women may need higher doses of drugs called angiotensin receptor blockers to lower blood pressure, because they have higher levels of proteins that cause the blood vessels to constrict, said Kathryn Sandberg, director of the Center for the Study of Sex Differences in Health, Aging and Disease at Georgetown.

Many researchers say data on these sex differences must be gathered at the very beginning of a drug’s development — even before trials on human subjects begin.

“The path to a new drug starts with the basic science — you study an animal model of the disease, and that’s where you discover a drug target,” Dr. Sandberg said. “But 90 percent of researchers are still studying male animal models of the disease.”

There have been improvements. In an interview, Dr. Robert Temple, with the Center for Drug Evaluation and Research at the F.D.A., said the agency’s new guidelines in 1993 called for studies of sex differences at the earliest stages of drug development, as well as for analysis of clinical trial data by sex.

He said early research on an irritable bowel syndrome drug, alosetron (Lotronex), suggested it would not be effective in men. As a result, only women were included in clinical trials, and it was approved only for women. (Its use is restricted now because of serious side effects.)

But some scientists say drug metabolism studies with only 10 or 15 subjects are too small to pick up sex differences. Even though more women participate in clinical trials than in the past, they are still underrepresented in trials for heart and kidney disease, according to one recent analysis, and even in cancer trials.

“The big problem is we’re not quite sure how much difference this makes,” Dr. Lindsey said. “We just don’t have a good handle on it.”

---

Readers may submit comments or questions for The Consumer by e-mail to consumer@nytimes.com.

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Federal Reserve holds steady on interest rates and stimulus effort

By Jim Puzzanghera

January 30, 2013, 11:54 a.m.

WASHINGTON -- With economic growth slowing in recent months, the Federal Reserve said Thursday it would keep short-term interest rates near zero and continue its latest bond-buying stimulus program.

Following a two-day meeting, Fed policymakers said recent information "suggests that growth in economic activity paused in recent months, in large part because of weather-related disruptions and other transitory factors."

Those disruptions included the Midwest drought and Superstorm Sandy.

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Photo: Federal Reserve Chairman Ben S. Bernanke

The statement from the Federal Open Market Committee, the central bank's policymaking arm, came after the Commerce Department unexpectedly reported the economy contracted at a 0.1% annual rate in the fourth quarter of last year.

It was the first time the economy shrank since the end of the great recession in 2009.

But most economists said the slowdown was an anomaly caused in part because of concerns about the fiscal cliff. They predicted the economy would grow about 2% in the first quarter of this year.

The closely watched wording of the Federal Open Market Committee's statement was a bit more pessimistic than after the last meeting in December. At that point, the Fed said economic activity and employment were expanding at a "moderate pace in recent months, apart from weather-related disruptions."

In September, the Fed launched its third round of bond buying to try to stimulate economic growth and reduce unemployment.

The central bank began an open-ended program to buy $85 billion in bonds a month to hold down long-term interest rates and boost business spending,

The Fed also said it anticipated short-term interest rates would remain near zero until the unemployment rate dropped to at least 6.5%, as long as inflation remained in check.

The unemployment rate was 7.8% in December and economists project it remained the same this month. The Labor Department will release the January jobs report Friday.

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Apple announces iPad with double storage capacity

(Reuters) – Apple Inc said on Tuesday that it will sell a version of its iPad tablet computer with 128 gigabytes of storage, which is twice the capacity of its existing models.

Apple, which has sold more than 120 million iPads so far, said that the new iPad will go on sale February 5, in black or white, for a suggested retail price of $ 799 for the iPad with just Wi-Fi model, and $ 929 for the version that also has a cellular wireless connection.

(Reporting By Sinead Carew; Editing by Gerald E. McCormick)

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Egyptian general warns against continued unrest

CAIRO — Egypt’s top military commander warned President Mohamed Morsi and opposition parties Tuesday to end days of bloodshed and unrest before the nation slides into chaos that may jeopardize the economy and “lead to the collapse of the state.”

The ominous statement from Gen. Abdel Fattah Sisi signaled that the military, which ruled Egypt for months before Morsi was elected in June, wanted to quickly stem an uprising against the Islamist-led government. At least 52 people have died in riots since Friday.

“The continuing conflict between political forces and their differences concerning the management of the country could lead to a collapse of the state and threaten future generations,” Sisi said on the army’s Facebook page. He added that political turmoil and attacks on state targets were a “real threat to the security of Egypt.”

Despite its much criticized rule, marked by political repression and human rights violations, the military is largely revered. It is regarded by many Egyptians as the single stabilizing force across a spectrum of failed institutions and Morsi’s authoritarian moves to consolidate the Muslim Brotherhood’s grip on power.

It did not appear the army was preparing to seize control of the country. The generals’ tenure running the government after the February 2011 toppling of Hosni Mubarak left them bitter and tainted the military’s reputation, especially after crackdowns on demonstrators. The army prefers playing behind-the-scenes power broker.

The statement, though, suggested the military was losing patience with protesters and questioning Morsi’s ability to contain the crisis. The army has been loyal to the president; Morsi supported a new constitution that gives the generals wide autonomy. But the Islamist president has been unable to sway protesters or the opposition away from conflict.

The military did not clarify how it “might interfere in coming days,” said Talaat Mosallam, a retired major general and security analyst. “Their experience before in politics was not a comfortable one. But their feeling that the political powers might be losing control compelled them to issue a statement.”

Troops have been deployed and given emergency arrest powers to guard public buildings and shipping docks in the vital coastal cities of Suez, Port Said and Ismailia. Ports in those towns serve the Suez Canal, whose stability is a potent economic symbol for foreign capitals and investors.

Violence and protests eased a bit on Tuesday. However, clashes between rock-throwing youths and police rumbled at the edges of Tahrir Square in Cairo. Unrest continued Suez and Port Said, where protesters defied curfews and the government had lost control amid burned police stations and well-armed residents.

The main opposition coalition, the National Salvation Front, has rejected Morsi’s call for political talks. The organization, headed by reformers, including Nobel Peace Prize laureate Mohamed ElBaradei, has accused the president and the Muslim Brotherhood of hijacking the revolution that overthrew Mubarak.

But the opposition’s influence on the streets is questionable. Many protesters criticize it as disorganized, divided and unable to articulate a galvanizing message. The opposition epitomizes a major shortcoming of the revolution: the absence of a charismatic figure capable of bridging political differences and fixing the economy.

The military’s statement highlighted the failure of the Interior Ministry, which controls the nation’s police forces, to keep order. The ministry backed Mubarak’s 30 years of repressive rule and lacks the reforms to gain the confidence of Egyptians. It is mistrusted by the Muslim Brotherhood, whose members for decades were persecuted and tortured by police.

The unrest has been further complicated by disparate interests converging around a protest movement. Peaceful demonstrations have often been overshadowed by young men and boys hurling stones and firebombs at police. Soccer fans, known as Ultras, have acted as shock troops. Looters and gunmen roam cities.

More recently an anarchist group calling itself the Black Bloc has battled security forces along barricades leading to the parliament. The country’s general prosecutor Tuesday called it a terrorist organization after the ransacking of the lobby in the Intercontinental Hotel near Tahrir Square. The Black Bloc denied it was involved.

Frightened hotel workers sent out tweets, including one that read: “SOS If anyone knows anyone in #Military #Police #Government, please send help! Thugs in Lobby.”

Hesham Abdel-Wahab, a hotel security guard, told the Ahram Online news website: “We called the police and requested they send forces. But when I spoke to the police, they just continued to ask me for my name. They were very hesitant. I kept saying to them that my name doesn't matter, we were under attack.”

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Special correspondent Reem Abdellatif contributed to this report.

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Dior: Jennifer Lawrence dress had no malfunction

LOS ANGELES (AP) — That was no wardrobe malfunction — that was couture.

When Jennifer Lawrence ascended the stairs to accept her SAG Award Sunday night, a bit of skin showed through the skirt of her gown, leading to some speculation that it had ripped.

Dior Couture told The Associated Press that wasn't so.

The design house said Lawrence's gown was designed by Raf Simons "with different levels of tulle and satin." That was what viewers saw on television when she lifted her gown to walk upstairs.

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Well: Ask Well: Squats for Aging Knees

You are already doing many things right, in terms of taking care of your aging knees. In particular, it sounds as if you are keeping your weight under control. Carrying extra pounds undoubtedly strains knees and contributes to pain and eventually arthritis.

You mention weight training, too, which is also valuable. Sturdy leg muscles, particularly those at the front and back of the thighs, stabilize the knee, says Joseph Hart, an assistant professor of kinesiology and certified athletic trainer at the University of Virginia, who often works with patients with knee pain.

An easy exercise to target those muscles is the squat. Although many of us have heard that squats harm knees, the exercise is actually “quite good for the knees, if you do the squats correctly,” Dr. Hart says. Simply stand with your legs shoulder-width apart and bend your legs until your thighs are almost, but not completely, parallel to the ground. Keep your upper body straight. Don’t bend forward, he says, since that movement can strain the knees. Try to complete 20 squats, using no weight at first. When that becomes easy, Dr. Hart suggests, hold a barbell with weights attached. Or simply clutch a full milk carton, which is my cheapskate’s squats routine.

Straight leg lifts are also useful for knee health. Sit on the floor with your back straight and one leg extended and the other bent toward your chest. In this position, lift the straight leg slightly off the ground and hold for 10 seconds. Repeat 10 to 20 times and then switch legs.

You can also find other exercises that target the knees in this video, “Increasing Knee Stability.”

Of course, before starting any exercise program, consult a physician, especially, Dr. Hart says, if your knees often ache, feel stiff or emit a strange, clicking noise, which could be symptoms of arthritis.

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Netflix plans $400-million bond offering

Netflix plans to raise $400 million in a bond offering to help position the company for further growth. (Gareth Cattermole / Getty Images)

By Dawn C. Chmielewski

January 29, 2013, 11:38 a.m.

Netflix Inc. plans to raise $400 million by selling eight-year notes, as the online video service positions itself for growth.

The company said it planned to use about $225 million from the offering to retire about $200 million in outstanding debt, and use the remaining proceeds for general corporate purposes, including investments, potential acquisitions and strategic transactions.

Chief Financial Officer David Wells talked about Netflix's plans to capitalize on the ability to get low-cost capital during a recent investor call. He said the cash could help finance more original series, such as "House of Cards," which debuts Feb. 1, if the program is a hit with subscribers.

"I would say this about the opportunity presented by the debt market, and the ability to get low-cost capital, and for us to preserve the flexibility," Wells said. "If we see massive success with originals, to preserve the flexibility, to expand that program, and to develop more down the road ... This is about long-term planning for the business."

Netflix's stock has been on the rise since the movie and television subscription service beat expectations in terms of domestic subscriber growth and earnings in its fourth quarter. It was trading at $168.23 at midday Tuesday, well above its 52-week low of $52.81.

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Netflix stock soars after fourth-quarter results top forecasts

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Crucial, long-overdue BlackBerry makeover arrives

TORONTO (AP) — The maker of the BlackBerry smartphone is promising a speedy browser, a superb typing experience and the ability to keep work and personal identities separate on the same phone, the fruit of a crucial, long-overdue makeover for the Canadian company.

Thorsten Heins, chief executive of Research In Motion Ltd., will reveal the first phone with the new BlackBerry 10 system in New York on Wednesday. Repeated delays have left the once-pioneering BlackBerry an afterthought in the shadow of Apple’s trend-setting iPhone and Google’s Android-driven devices.

Now, there’s some optimism. Previews of the software have gotten favorable reviews on blogs. Financial analysts are starting to see some slight room for a comeback. RIM‘s stock has nearly tripled to about $ 16.30 from a nine-year low in September, though it’s still nearly 90 percent below its 2008 peak of $ 147.

Most analysts consider a BlackBerry 10 success to be crucial for the company’s long-term viability.

“The old models are becoming obsolete quickly,” BGC Financial analyst Colin Gillis said. “There is still a big user base but it’s going to rotate off. The question is: Where do they rotate to?”

The BlackBerry, pioneered in 1999, has been the dominant smartphone for on-the-go business people. Corporate information-technology managers like the phones because they’re relatively secure and easy to manage.

The BlackBerry has also crossed over to consumers. President Barack Obama couldn’t bear to part with it when he took office. Oprah Winfrey declared it one of her “favorite things.” People got so addicted that the device was nicknamed “the CrackBerry.”

But when the iPhone came out in 2007, it showed that phones can do much more than email and phone calls. They can play games, music and movies. Android came along to offer even more choices. Though IT managers still love BlackBerrys, employees were bringing their own devices to the workplace — a trend Heins acknowledged RIM was slow to adapt to.

Suddenly, the BlackBerry looked ancient.

Even as BlackBerry sales continued to grow in many parts of the world, many BlackBerry users in North America switched to iPhones and Android devices. BlackBerry’s worldwide subscriber based peaked at 80 million in the quarter that ended Sept. 1, before dropping to 79 million in the most-recent quarter. In the U.S., according to research firm IDC, shipments of BlackBerry phones plummeted from 46 percent of the market in 2008 to 2 percent in 2012.

RIM promised a new system to catch up, using technology it got through its 2010 purchase of QNX Software Systems. RIM initially said BlackBerry 10 would come by early 2012, but then the company changed that to late 2012. A few months later, that date was pushed further, to early 2013, missing the lucrative holiday season. The holdup helped wipe out more than $ 70 billion in shareholder wealth and 5,000 jobs.

Although executives have been providing a glimpse at some of BlackBerry 10′s new features for months, Heins will finally showcase a complete system at Wednesday’s event. Devices will go on sale soon after that.

RIM redesigned the system to embrace the multimedia, apps and touch-screen experience prevalent today.

“Historically there have been areas that have not been our strongest points,” Rick Costanzo, RIM’s executive vice president of global sales, said in an interview. “Not only have we caught up, but we may even be better than some of the competition now.”

Costanzo said “no one else can touch” what RIM’s new system offers.

The new operating system promises better multitasking than either the iPhone or Android. Simply swipe a finger across the phone’s display screen to switch to another program.

All emails and notifications from such applications as Twitter and Facebook go to the BlackBerry Hub, a nerve center accessible with a finger swipe even if you have another application open. One can peek into it and open an email, or return to the previous application without opening the email.

“You are not going in and out of applications; you’re flowing through applications with one simple gesture of your finger,” Costanzo said. “You can leave applications running. You can effortlessly flow between them. So that’s completely unique to us.”

That said, multitasking will be limited and won’t allow for extensive use of apps side by side, as is typically permitted on traditional computers. If you’re watching a video, it will still run while you check for email. But it will pause if you decide to open an email and resume when you are done.

The BlackBerry’s touch-screen keyboard promises to learn a user’s writing style and suggest words and phrases to complete, going beyond typo corrections offered by rivals. See the one you want, and flick it up to the message area. Costanzo said that “BlackBerry offers the best keyboard, period.”

Gus Papageorgiou, a Scotiabank financial analyst who has tried it out, agreed with that assessment and said the keyboard even learns and adjusts to your thumb placements.

The first BlackBerry 10 phone will have only a touch screen. RIM has said it will release a version with a physical keyboard soon after that. That’s an area RIM has excelled at, and it’s one reason many BlackBerry users have remained loyal despite temptations to switch.

Another distinguishing feature will be the BlackBerry Balance, which allows two personas on the same device. Businesses can keep their data secure without forcing employees to get a second device for personal use. For instance, IT managers can prevent personal apps from running inside corporate firewalls, but those managers won’t have access to personal data on the device.

With Balance, “you can just switch from work to personal mode,” Papageorgiou said. “I think that is something that will attract a lot of people.”

RIM is also claiming that the BlackBerry 10′s browser will be speedy, even faster than browsers for laptop and desktop computers. According to Papageorgiou, early, independent tests between the BlackBerry 10 and the iPhone support that claim.

Regardless of BlackBerry 10′s advances, though, the new system will face a key shortcoming: It won’t have as many apps written by outside companies and individuals as the iPhone and Android. RIM has said it plans to launch BlackBerry 10 with more than 70,000 apps, including those developed for RIM’s PlayBook tablet, first released in 2011. Even so, that’s just a tenth of what the iPhone and Android offer. Papageorgiou said the initial group will include the most popular ones such as Twitter and Facebook. But RIM will have to persuade others to make a BlackBerry version, when they are already struggling to keep up with both the iPhone and Android.

Like many analysts, Papageorgiou recently upgraded RIM’s stock, but cautions that longtime BlackBerry users will have to get used to a whole new operating system.

He said RIM can be successful if about a third of current subscribers upgrade and if the company can get 4 million new users overseas, especially in countries where the BlackBerry has remained popular. IDC said smartphone shipments grew 44 percent in 2012. If those trends continue, it will be possible for the BlackBerry to grow even if iPhone and Android users don’t switch.

“This doesn’t have to be the best smartphone on the planet to be a success for RIM,” he said. “I think the big question though is, if it fails, is it just too late? Are the other two ecosystems just so advanced that no one can catch up? That’s a big risk.”

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'Argo' producer scours for the next stranger-than-fiction story

Hunched over a desk in his spartan Westwood apartment, David Klawans squints at his computer monitor and knits his brow in concentration. "I'm perusing," he says.

His eyes dart between headlines almost indecipherable on a Web page displaying about 800 stamp-sized images of newspapers from 90 different countries.

"Two kids running? What's that?" he exclaims before clicking on a photo. "Oh, it's refugees. Whatever. Moving on."

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Nearly every day, for upward of 10-hour stretches, the independent film producer speed-reads police blogs, articles from RSS feeds and niche-interest journals in dogged pursuit of an elusive prize: a story on which to base his next movie.

His biggest hit to date is "Argo." Before the film landed seven Oscar nominations (including one for best picture) and two Golden Globes (including best drama picture), before it generated more than $180 million in worldwide grosses, "Argo" existed as a declassified story in the quarterly CIA journal Studies in Intelligence, which Klawans happens to have been perusing one day in 1998.

"It's like going on the beach with a metal detector," the self-described news junkie says of his process. "Like Kanye West looks through records to sample on his songs, I'm looking for stories to turn into films."

Klawans, 44, has established himself as Hollywood's least likely movie macher by heeding the advice of his mentor, the old-school producer David Brown ("Jaws," "A Few Good Men"): "Read everything you can get your hands on."

Indefatigable in his quest to root out oddball, overlooked true-life stories, Klawans spins material most others ignore into cinematic gold.

OSCAR WATCH: "ARGO"

"Argo" took nearly 14 years to reach the big screen after Klawans read about CIA exfiltration expert Tony Mendez's rescue of six American diplomats hiding in Tehran during the 1979 Iran hostage crisis. Mendez (portrayed in the movie by "Argo's" director, Ben Affleck) posed the group as Canadian filmmakers scouting locations for a science-fiction film, created a fictitious production company and planted articles about the bogus project in Hollywood trade papers.

Throughout the '90s Klawans was scraping by as a production assistant for an L.A.-based Japanese TV commercial firm. He didn't own a car, so he bicycled to UCLA's magazine archive to check the story. In microfiche files, he came across the CIA's planted articles in the Hollywood Reporter and Variety from January 1980. "My jaw dropped," he says.

Problem was, Mendez already had representation at Creative Artists Agency and was preparing to publish a memoir, "The Master of Disguise." Even so, Klawans persuaded Mendez to let him attempt to set up a movie project. He eventually bought the rights to Mendez's life story as well.

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"I'm cycling to pitch meetings wearing a backpack with a change of clothes. It's summertime and I'm sweating. And I'm getting to know studio security. They call me 'bike boy,'" remembers Klawans, who would switch from bike to business attire outside the studio gates. "I would basically throw my backpack behind a bush — I was embarrassed to look like a messenger guy."

The New York University film school graduate was born in Chicago. His family moved to Belgium when he was 2 and he grew up in Europe and the U.S. consuming a steady diet of sci-fi and fantasy films including "Star Wars."

He came close to setting up the "Argo" project as a cable TV movie. But when that deal fell through, Klawans says, "it hit me that Tony had planted stories in Variety and Hollywood Reporter as a cover. For the CIA, it's all about illusions and perception. I thought, 'That's what I'm going to do. I'm going to plant an "Argo" story in a magazine.'"

The producer had met former L.A. Weekly staff writer and "This American Life" contributor Joshuah Bearman through friends who thought the two shared an appreciation for offbeat material. Bearman also had experience turning a magazine story into a movie; an article he reported for Harper's became the 2007 documentary "The King of Kong: A Fistful of Quarters," about two die-hard video game players vying for the world's highest score in the vintage arcade game "Donkey Kong."

Klawans handed over his research and contacts to Bearman and proposed that the journalist write "Argo" as a magazine article that would entice movie backers.

Bearman landed an assignment from Wired magazine, then interviewed everyone he could: Mendez, officials in the State Department with knowledge of the exfiltration and Ken Taylor, the Canadian ambassador to Iran who housed some of the fugitive American diplomats, as well as the six embassy "houseguests."

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