New Hope For ‘Man on Fire Syndrome’

Pamela Costa has never known a day without agonizing pain in her legs and feet.

At age 11, the Seattle native was diagnosed with inherited erythromelalgia, a genetic condition that causes such severe pain and redness some call it “Man on Fire Syndrome.”

“Think of the feeling that you get when you come in from the cold and your hands and feet are rewarming too fast,” said Costa, 47. “I have that feeling all of the time.”

Inherited erythromelalgia is a disease of small nerves and blood vessels that causes severe pain in response to heat, pressure, exertion or stress.

“These people feel excruciating, scalding pain while putting on shoes or putting on a sweater,” said Dr. Stephen Waxman, a neuroscientist at Yale University and the West Haven Veterans Affairs Hospital. “They will keep their feet on ice to the point of getting gangrene, just to relieve the sensation.”

When Costa was growing up, playing outside would trigger the unbearable burning sensation.

“I used to come in from recess and just hold my hands on the cool metal of my school desk,” said Costa, who has more than two dozen relatives with the same affliction. “I have had cousins suffer devastating injuries from over-cooling themselves.”

Although the disease is rare, researchers are searching for clues to its cause with hopes of uncovering treatments for chronic pain of all kinds. The story starts at the molecular level within tiny nerves that conduct pain signals.

An Overactive Channel Protein

Pain comes in different forms, depending on the type of nerve that senses it. And for chronic pain patients, the pain is not quick and specific, but instead slow and sharp.

This slow pain is transmitted from the limbs and body to the brain along small nerves in the spinal cord called C-fibers. Messages move along these nerve fibers due to the action of special proteins in their membranes called channels. One specific type of channel is the Nav1.7 sodium channel, which is present in great numbers in the C-fibers of the spinal cord.

Work by Waxman and others has shown that patients with inherited erythromelalgia have a defect in their Nav1.7 channels that allows too many sodium ions to enter the C-fibers, causing an increase in the sensitivity of the nerves.

The specific atomic structure of the Nav1.7 channel has been modeled by Waxman’s lab, and the results are detailed in the current issue of Nature Communications. Armed with this new model of the Nav1.7 channel, the lab has been able to show why some patients with inherited erythromelalgia respond well to an anti-epileptic drug called Carbamazepine.

Furthermore, in studying the channel structure in many different people, Waxman and colleagues have found variations in the channel from person to person. These variations may cause some people to be more likely to experience chronic pain than others.

A New Drug Target

Patients with a completely defective Nav1.7 suffer from the opposite condition, known as congenital indifference to pain. These people do not experience pain at all, with case reports of being able to walk on hot coals without pain.

As the role of Nav1.7 in the mechanism for pain sensation becomes clearer, biotechnology and pharmaceutical companies will likely take notice, according to Waxman.

“I anticipate a race to develop Nav1.7 specific blockers,” he said.

Current drug therapies for pain include medicines like morphine, as well as aspirin and ibuprofen. While all of these decrease the sensation of pain, they also interact with other tissues such as the brain, heart and stomach, causing side effects.

Nav1.7 does not appear to be present in large quantities outside of the C-fibers of the spinal cord. As such, new drugs targeting this protein could herald a new class of pain treatments with many fewer side effects than our current drugs for pain.

Costa said she hopes to see a day where such a medicine would be available to her, providing her with full relief for the first time in her life.

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General investigated for emails to Petraeus friend

PERTH, Australia (AP) — In a new twist to the Gen. David Petraeus sex scandal, the Pentagon said Tuesday that the top American commander in Afghanistan, Gen. John Allen, is under investigation for alleged “inappropriate communications” with a woman who is said to have received threatening emails from Paula Broadwell, the woman with whom Petraeus had an extramarital affair.

Defense Secretary Leon Panetta said in a written statement issued to reporters aboard his aircraft, en route from Honolulu to Perth, Australia, that the FBI referred the matter to the Pentagon on Sunday.

Panetta said that he ordered a Pentagon investigation of Allen on Monday.

A senior defense official traveling with Panetta said Allen’s communications were with Jill Kelley, who has been described as an unpaid social liaison at MacDill Air Force Base, Fla., which is headquarters to the U.S. Central Command. She is not a U.S. government employee.

Kelley is said to have received threatening emails from Broadwell, who is Petraeus’ biographer and who had an extramarital affair with Petraeus that reportedly began after he became CIA director in September 2011.

Petraeus resigned as CIA director on Friday.

Allen, a four-star Marine general, succeeded Petraeus as the top American commander in Afghanistan in July 2011.

The senior official, who discussed the matter only on condition of anonymity because it is under investigation, said Panetta believed it was prudent to launch a Pentagon investigation, although the official would not explain the nature of Allen’s problematic communications.

The official said 20,000 to 30,000 pages of emails and other documents from Allen’s communications with Kelley between 2010 and 2012 are under review. He would not say whether they involved sexual matters or whether they are thought to include unauthorized disclosures of classified information. He said he did not know whether Petraeus is mentioned in the emails.

“Gen. Allen disputes that he has engaged in any wrongdoing in this matter,” the official said. He said Allen currently is in Washington.

Panetta said that while the matter is being investigated by the Defense Department Inspector General, Allen will remain in his post as commander of the International Security Assistance Force, based in Kabul. He praised Allen as having been instrumental in making progress in the war.

The FBI’s decision to refer the Allen matter to the Pentagon rather than keep it itself, combined with Panetta’s decision to allow Allen to continue as Afghanistan commander without a suspension, suggested strongly that officials viewed whatever happened as a possible infraction of military rules rather than a violation of federal criminal law.

Allen was Deputy Commander of Central Command, based in Tampa, prior to taking over in Afghanistan. He also is a veteran of the Iraq war.

In the meantime, Panetta said, Allen’s nomination to be the next commander of U.S. European Command and the commander of NATO forces in Europe has been put on hold “until the relevant facts are determined.” He had been expected to take that new post in early 2013, if confirmed by the Senate, as had been widely expected.

Panetta said President Barack Obama was consulted and agreed that Allen’s nomination should be put on hold. Allen was to testify at his confirmation hearing before the Senate Armed Services Committee on Thursday. Panetta said he asked committee leaders to delay that hearing.

NATO officials had no comment about the delay in Allen’s appointment.

“We have seen Secretary Panetta‘s statement,” NATO spokeswoman Carmen Romero said in Brussels. “It is a U.S. investigation.”

Panetta also said he wants the Senate Armed Services Committee to act promptly on Obama’s nomination of Gen. Joseph Dunford to succeed Allen as commander in Afghanistan. That nomination was made several weeks ago. Dunford’s hearing is also scheduled for Thursday.

___

Associated Press writer Slobodan Lekic in Kabul, Afghanistan, contributed to this report.

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New Lumia phones seen winning Nokia more time

HELSINKI (Reuters) – Nokia‘s new Lumia smartphones are trickling into the market and early signs suggest they may sell well enough to give the handset maker more time in its fight against industry leaders Samsung and Apple.

But investors shouldn’t expect a quick turnaround for the struggling Finnish cellphone maker, with rival gadgets like mini tablet computers vying for consumers’ attention, analysts said.

“Positive reviews are a great start but as we have seen many times before these won’t deliver strong sales volumes on their own,” said Pete Cunningham, an analyst at research firm Canalys.

Successful sales of the latest Lumia 920 and 820 models are crucial for Nokia’s survival. The former market leader is burning through cash while it loses share in both high-end smartphones and cheaper handsets.

FIM Securities analyst Michael Schroder forecast Nokia will sell 1-3 million of the new models this quarter. It sold 2.9 million older Lumia models in the third quarter, compared to Apple’s sales of around 26.6 million iPhones in the same period.

“In any case the uptake will not be massive,” he predicted.

Lumia’s sales could serve a verdict on Chief Executive Stephen Elop‘s decision in February 2011 to partner with Microsoft instead of using Google‘s Android or continuing to develop Nokia’s own operating system.

Investors had feared poor reviews and weak sales could bring an end to the company’s smartphone business early next year.

So far, consumer reviews seem to favor the feel and look of the new models, which include high-definition cameras and the latest Microsoft Windows Phone 8 software.

“It (the Lumia 920) is very similar in appearance to the Lumia 900, but has curved glass, rounded edges, and curved back so it feels great in your hand. It is a dense device, but if you look at all the pros and cons the heft is worth it,” said a reviewer for tech website ZDNet.

That’s an improvement from the market’s reaction when the new model was first unveiled. The shares slumped 13 percent that day with investors citing a lack of a “wow” factor.

MAKE OR BREAK

Nokia is taking a gradual approach to launching the phones, and availability is expected to vary by market for the next few weeks, compared with Apple’s iPhone models which usually go on sale on the same day to global fanfare.

“While we are very impressed with the hardware features of the Lumia 920 and the improved software functionality of Windows Phone 8, we believe a focused launch to drive steady sales growth is necessary,” said Canaccord Genuity analyst Michael Walkley.

In Canada, one of the earliest launch markets, carrier Rogers Communications has trained its sales staff more to sell the latest Lumias than the previous models, said John Boynton, Rogers’ executive vice president of marketing.

He predicted the phones would be popular with first-time smartphone users, thanks to homescreens with tile-like icons designed to help users navigate applications and functions.

“They’re a little nervous at some of the more complex smartphones that are out there,” he said. “The tile format is a really, really simplified way for people to get comfortable using smartphones.”

In France, retail staff have become more confident in explaining Windows Phones to their customers, according to Laurent Lame, devices marketing chief at SFR which is the country’s second-biggest mobile operator.

“They know the product better after six months of good sales of the Lumia 610,” Lame said, adding he was now more optimistic about the Nokia-Microsoft partnership. “For once, with Windows 8, we are not starting from zero.”

Telefonica Deutschland Chief Executive Rene Schuster said he was “very, very pleased” with the early progress of Lumia sales.

Some retailers were more cautious, however, and in some cities there were no demonstration models for customers to test.

A salesman in an O2 store at the Zeil, Frankfurt’s busiest shopping area, said the store could take orders for the phone but could not show it. Demand was “okay, but not huge,” he said.

Analysts also expect tough competition during the pre-Christmas shopping season from the likes of Samsung’s Galaxy S III and Apple’s iPhone 5. Taiwan’s HTC has also introduced smartphones running Windows Phone 8 software.

Other rival gadgets include Apple’s iPad mini as well as cheaper tablets from Google and Amazon.

The stakes could not be higher for Nokia’s Elop, who said in February 2011 the company’s transition would take two years.

“This is absolutely a make-or-break phone for the Windows Phone strategy,” FIM Securities’ Schroder said. “If it fails, they have to take a whole new course.” (Additional reporting by Allison Martell in Toronto, Leila Abboud in Paris, Harro Ten Wolde in Frankfurt and Tarmo Virki in Helsinki; Editing by Mark Potter)

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Day-Lewis heeded inner ear to find Lincoln’s voice

LOS ANGELES (AP) — A towering figure such as Abraham Lincoln, who stood 6 feet 4 and was one of history’s master orators, must have had a booming voice to match, right? Not in Daniel Day-Lewis‘ interpretation.

Day-Lewis, who plays the 16th president in Steven Spielberg‘s epic film biography “Lincoln,” which goes into wide release this weekend, settled on a higher, softer voice, saying it’s more true to descriptions of how the man actually spoke.

“There are numerous accounts, contemporary accounts, of his speaking voice. They tend to imply that it was fairly high, in a high register, which I believe allowed him to reach greater numbers of people when he was speaking publicly,” Day-Lewis said in an interview. “Because the higher registers tend to reach farther than the lower tones, so that would have been useful to him.”

“Lincoln” is just the fifth film in the last 15 years for Day-Lewis, a two-time Academy Award winner for best actor (“My Left Foot” and “There Will Be Blood”). Much of his pickiness stems from a need to understand characters intimately enough to feel that he’s actually living out their experiences.

The soft, reedy voice of his Lincoln grew out of that preparation.

“I don’t separate vocal work, and I don’t dismember a character into its component parts and then kind of bolt it all together, and off you go,” Day-Lewis said. “I tend to try and allow things to happen slowly, over a long period of time. As I feel I’m growing into a sense of that life, if I’m lucky, I begin to hear a voice.

“And I don’t mean in a supernatural sense. I begin to hear the sound of a voice, and if I like the sound of that, I live with that for a while in my mind’s ear, whatever one might call it, my inner ear, and then I set about trying to reproduce that.”

Lincoln himself likely learned to use his voice to his advantage depending on the situation, Day-Lewis said.

“He was a supreme politician. I’ve no doubt in my mind that when you think of all the influences in his life, from his childhood in Kentucky and Indiana and a good part of his younger life in southern Illinois, that the sounds of all those regions would have come together in him somehow.

“And I feel that he probably learned how to play with his voice in public and use it in certain ways in certain places and in certain other ways in other places. Especially in the manner in which he expressed himself. I think, I’ve no doubt that he was conscious enough of his image.”

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War uproots 2.5 million Syrians, aid groups say

GENEVA (Reuters) – At least 2.5 million Syrians are believed to have fled their homes because of civil war, aid groups said on Tuesday, more than double previous estimates.

The figure comes from the Syrian Arab Red Crescent, whose volunteers are on the frontlines of the 20-month conflict, delivering aid supplies and evacuating wounded.

“The figure they are using is 2.5 million. If anything, they believe it could be more, that this is a very conservative estimate,” Melissa Fleming, chief spokeswoman of the U.N. High Commissioner for Refugees (UNHCR), told a news briefing.

“So people are moving, people are really on the run, hiding. They are difficult to count and to access,” she said.

Aid agencies had previously thought there were around 1.2 million internally displaced Syrians.

Only 5 percent of the 2.5 million are believed to be living in public facilities, including warehouses and schools, said Fleming. The rest are staying with host families, making it more difficult to count them.

In recent days, air strikes on the town of Ras al-Ain near the Turkish border have caused some of the biggest refugee movements of the conflict.

The United Nations said on Friday that up to 4 million people inside Syria will need humanitarian aid by early next year when the country is in the grip of winter, up from 2.5 million now whose needs are not fully met.

For now, the U.N. World Food Programme (WFP) says its food rations are reaching some 1.5 million. The UNHCR aims to provide assistance to 500,000 in Syria by the end of the year, mainly blankets, clothing, cooking kits and jerry cans, Fleming said.

“Unfortunately the recent deliveries have been very difficult, marred by violence and insecurity also spreading to parts of the country that used to be relatively calm,” she said.

A Syrian Arab Red Crescent warehouse in Aleppo was apparently hit by a shell, burning 13,000 blankets, she said. Unknown armed men hijacked a truck carrying 600 blankets on its way to Adra, outside Damascus.

The UNHCR has temporarily withdrawn about half of its 12 staff from north-eastern Hassaka province due to fierce fighting and insecurity, Fleming said.

“We see corresponding movement of populations there, Syrian Kurds for the most part, across the border into Iraq,” she said.

More than 407,000 Syrian refugees have registered or await registration in the surrounding region – Lebanon, Turkey, Jordan and Iraq – and more are fleeing every day, according to UNHCR.

(Editing by Tom Pfeiffer)

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'Inappropriate’ emails, ‘shirtless’ photos

Paula Broadwell and Gen. David Petraeus in July of 2011. (Photo by ISAF via Getty Images)It seemed the story behind Gen. David Petraeus' resignation as director of the CIA  couldn't get stranger. New reports, however, now indicate that Marine Gen. John Allen, another well-respected, high-ranking general, might be involved in the growing scandal.

On the surface, the case so far involves: the FBI; a slew of allegedly inappropriate emails (between  Petraeus and his biographer, Paula Broadwell, Allen and socialite Jill Kelley, and allegedly threatening ones Broadwell sent to Kelley); the FBI agent who started the probe, who's now being investigated for sending "shirtless" photos to Kelley; and, as reported by the New York Post Tuesday morning, a child custody battle involving Kelley's twin sister that somehow allegedly concerns both Petraeus and Allen.

To help sort things out, here's a rundown of events, and where things currently stand.

Jill Kelley, a 37-year-old from Tampa, Fla., who organized local social events for the military as a volunteer, became friends with Petraeus and his family when he was stationed in Florida. Last spring, she began receiving harassing emails from an anonymous account, and alerted a friend who worked for the FBI.

The FBI began an investigation, which eventually uncovered an affair between Petraeus and Broadwell, both of who are married. The FBI believes Broadwell sent the harassing emails to Kelley because she perceived her to be a rival for Petraeus' affections.

The FBI found something else during the inquiry: 20,000 to 30,000 pages of emails and other communications between Kelley and Allen, the top commander in Afghanistan and a nominee to become the new NATO supreme allied commander for Europe.

A senior defense official has told the Washington Post that the emails were "potentially inappropriate." Other sources strongly denied to the Post that anything inappropriate ever happened between Allen and Kelley, but said that Allen may have used terms of endearment like "sweetheart" to refer to Kelley in his emails to her. The source said Allen, who is married, is "embarrassed" by this, but did not have an affair with her. Allen also received an email from the same account that was harassing Kelley, though it's unclear what the email said.

The Tampa party planner, who is married and has three children, is also at the center of another bizarre twist in the case. The Wall Street Journal reported Monday night that Kelley's FBI agent friend was taken off the Petraeus case and is currently being investigated because his superiors discovered that he sent "shirtless" photos to Kelley before the probe started. After the agent was removed from the case, the agent contacted Washington Rep. David Reichert to warn him that he thought FBI leaders would sweep the investigation under the rug.

Meanwhile, the Daily Beast, citing an anonymous source, reports that the harassing emails allegedly sent from Broadwell to Kelley did not say "stay away from my guy" as previously reported, and did not even directly reference Petraeus. The source described the tone of the emails as "more like, 'Who do you think you are? You parade around the base. You need to take it down a notch.'" The Wall Street Journal reported that one email, without elaborating, asked Kelley if her husband knew what she was doing. Another said the sender knew Kelley had touched "him," without specifying who the "him" was.

And, the AP has uncovered the trick Broadwell and Petraeus used to email each other without creating an online trail. The pair set up anonymous email accounts and drafted emails to each other without ever pushing "send." Each one could log on to the other account and click the "drafts" folder to see if a message had been left for them. This avoids creating an easily traceable email trail, the AP reported.

One question  the Daily Beast raised is why the FBI investigated the harassing emails sent to Kelley in the first place. There were no overt threats, such as "I'll kill you," in the emails, and some wonder if  Kelley's friendship with the FBI agent may be why the agency  investigated what seemed like a humdrum case better suited to local authorities.

Broadwell's father, for one, told the New York Daily News that he thinks the scandal is a smokescreen for a bigger story. "This is about something else entirely, and the truth will come out," Broadwell's father, Paul Krantz, told the Daily News. "There is a lot more that is going to come out."

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New Lumia phones seen winning Nokia more time

HELSINKI (Reuters) – Nokia‘s new Lumia smartphones are trickling into the market and early signs suggest they may sell well enough to give the handset maker more time in its fight against industry leaders Samsung and Apple.

But investors shouldn’t expect a quick turnaround for the struggling Finnish cellphone maker, with rival gadgets like mini tablet computers vying for consumers’ attention, analysts said.

“Positive reviews are a great start but as we have seen many times before these won’t deliver strong sales volumes on their own,” said Pete Cunningham, an analyst at research firm Canalys.

Successful sales of the latest Lumia 920 and 820 models are crucial for Nokia’s survival. The former market leader is burning through cash while it loses share in both high-end smartphones and cheaper handsets.

FIM Securities analyst Michael Schroder forecast Nokia will sell 1-3 million of the new models this quarter. It sold 2.9 million older Lumia models in the third quarter, compared to Apple’s sales of around 26.6 million iPhones in the same period.

“In any case the uptake will not be massive,” he predicted.

Lumia’s sales could serve a verdict on Chief Executive Stephen Elop‘s decision in February 2011 to partner with Microsoft instead of using Google‘s Android or continuing to develop Nokia’s own operating system.

Investors had feared poor reviews and weak sales could bring an end to the company’s smartphone business early next year.

So far, consumer reviews seem to favor the feel and look of the new models, which include high-definition cameras and the latest Microsoft Windows Phone 8 software.

“It (the Lumia 920) is very similar in appearance to the Lumia 900, but has curved glass, rounded edges, and curved back so it feels great in your hand. It is a dense device, but if you look at all the pros and cons the heft is worth it,” said a reviewer for tech website ZDNet.

That’s an improvement from the market’s reaction when the new model was first unveiled. The shares slumped 13 percent that day with investors citing a lack of a “wow” factor.

MAKE OR BREAK

Nokia is taking a gradual approach to launching the phones, and availability is expected to vary by market for the next few weeks, compared with Apple’s iPhone models which usually go on sale on the same day to global fanfare.

“While we are very impressed with the hardware features of the Lumia 920 and the improved software functionality of Windows Phone 8, we believe a focused launch to drive steady sales growth is necessary,” said Canaccord Genuity analyst Michael Walkley.

In Canada, one of the earliest launch markets, carrier Rogers Communications has trained its sales staff more to sell the latest Lumias than the previous models, said John Boynton, Rogers’ executive vice president of marketing.

He predicted the phones would be popular with first-time smartphone users, thanks to homescreens with tile-like icons designed to help users navigate applications and functions.

“They’re a little nervous at some of the more complex smartphones that are out there,” he said. “The tile format is a really, really simplified way for people to get comfortable using smartphones.”

In France, retail staff have become more confident in explaining Windows Phones to their customers, according to Laurent Lame, devices marketing chief at SFR which is the country’s second-biggest mobile operator.

“They know the product better after six months of good sales of the Lumia 610,” Lame said, adding he was now more optimistic about the Nokia-Microsoft partnership. “For once, with Windows 8, we are not starting from zero.”

Telefonica Deutschland Chief Executive Rene Schuster said he was “very, very pleased” with the early progress of Lumia sales.

Some retailers were more cautious, however, and in some cities there were no demonstration models for customers to test.

A salesman in an O2 store at the Zeil, Frankfurt’s busiest shopping area, said the store could take orders for the phone but could not show it. Demand was “okay, but not huge,” he said.

Analysts also expect tough competition during the pre-Christmas shopping season from the likes of Samsung’s Galaxy S III and Apple’s iPhone 5. Taiwan’s HTC has also introduced smartphones running Windows Phone 8 software.

Other rival gadgets include Apple’s iPad mini as well as cheaper tablets from Google and Amazon.

The stakes could not be higher for Nokia’s Elop, who said in February 2011 the company’s transition would take two years.

“This is absolutely a make-or-break phone for the Windows Phone strategy,” FIM Securities’ Schroder said. “If it fails, they have to take a whole new course.” (Additional reporting by Allison Martell in Toronto, Leila Abboud in Paris, Harro Ten Wolde in Frankfurt and Tarmo Virki in Helsinki; Editing by Mark Potter)

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What is Gen. John Allen's involvement in Petraeus scandal?

Gen. John Allen, commander of the International Security Assistance Force in Afghanistan, is under investigation for alleged "inappropriate communications" with Jill Kelley, the woman who is said to have received threatening emails from Paula Broadwell, the woman with whom former CIA Director David Petraeus had an extramarital affair.

The FBI has uncovered "potentially inappropriate" emails between Allen and Kelly, according to a senior U.S. defense official who is traveling with Defense Secretary Leon Panetta. The department is reviewing between 20,000 and 30,000 documents connected to this matter, the official said. The email exchanges between Kelley and Allen took place from 2010 to 2012.

Panetta says the FBI referred the matter to the Pentagon on Sunday, according to a statement he released Tuesday while en route to Perth, Australia. Panetta says he ordered the Pentagon inspector general to investigate Allen on Monday.

See the timeline of the entire Petraeus/Broadwell affair HERE.

Allen disputes that he has engaged in any wrongdoing in this matter, according to the official.

Allen, a four-star Marine general, succeeded Petraeus as the top American commander in Afghanistan in July 2011.

In the meantime, Panetta said, Allen's nomination to be the next commander of U.S. European Command and the commander of NATO forces in Europe has been put on hold "until the relevant facts are determined." He had been expected to take that new post in early 2013, if confirmed by the Senate, as had been widely expected.

Allen was supposed to appear before a Senate confirmation hearing this Thursday alongside his designated replacement, Marine Gen. Joseph Dunford. Panetta has asked the Senate Armed Services Committee hearing to delay Allen's hearing, but proceed with Dunford's nomination.

Panetta said President Obama has agreed to put Allen's nomination on hold until the facts are determined. Panetta said that while the matter is being investigated by the Defense Department IG, Allen will remain in his post as commander of the International Security Assistance Force, based in Kabul.

The senior Defense official said, "We'll have to let the process follow its course. As I said, and you'll see in the Secretary's statement, we believe that General Allen is entitled to due process. We need to see where the facts lead in this matter before jumping to any conclusions whatsoever."

The official added, "We're in the very early stages of reviewing the documents right now. This matter has been referred to the IG, the IG will do a thorough investigation of the documents."

Kelley is said to have received threatening emails from Broadwell, who is Petraeus' biographer and who had an extramarital affair with Petraeus that reportedly began two months after he became CIA director in September 2011.

Petraeus resigned as CIA director on Friday citing the affair as his reason for stepping down from his post.

FBI agents spent more than four hours at Broadwell's home in North Carolina Monday night to carry out a consensual search that had been arranged with her lawyers, law enforcement sources said. The search was to locate additional classified material on computers or documents in the home, the sources said.

Agents left the house with a desktop computer, cardboard boxes and a briefcase. They walked through the open garage of Broadwell's house and knocked at a side door before entering the home. One person was taking photographs of the house and its garage as members of the news media watched.

Broadwell appears to be cooperating with investigators in an effort to make this go away, to show that she has nothing else to hide, the sources said.

An assistant to Washington lawyer Robert F. Muse told ABC News that Muse is representing Broadwell. Muse works for the same firm as the lawyer who represented Monica Lewinsky.

The firm, Stein, Mitchell, Muse & Cipollone, boasts such high-profile clients as Lewinsky, former Sen. Bob Packwood, R-Ore., AFL-CIO officials and Ambassador Lewis Tambs in the Iran-Contra Investigation.

Petraeus could possibly face military prosecution for adultery if officials turn up any evidence to counter his apparent claims that the affair began after he left the military.

A friend of Petraeus, retired U.S. Army Col. Steve Boylan, told ABC News, that the affair began several months after his retirement from the Army in August 2011 and ended four months ago.

Broadwell, 40, had extraordinary access to the 60-year-old general during six trips she took to Afghanistan as his official biographer, a plum assignment for a novice writer.

The timeline of the relationship, according to Petraeus, would mean that he was carrying on the affair for the majority of his tenure at the CIA, where he began as director Sept. 6, 2011. If he carried on the affair while serving in the Army, however, Petraeus could face charges, according to Article 134 of the Uniform Code of Military Justice, which reprimands conduct "of a nature to bring discredit upon the armed forces."

As the details of the investigation launched by the FBI unraveled this weekend, it became clear that the woman at the heart of the inquiry that led to Petraeus' downfall had been identified as Jill Kelley, a Florida woman who volunteers to help the military. She is a family friend of Petraeus, who Broadwell apparently felt threatened by.

Kelley and her husband are longtime supporters of the military, and six months ago she was named "Honorary Ambassador to Central Command" for her volunteer work with the military. Officials say Kelley is not romantically linked to Petraeus, but befriended the general and his wife when he was stationed in Florida. The Kelleys spent Christmases in group settings with the Petraeuses and visited them in Washington D.C., where Kelley's sister and her son live.

"We and our family have been friends with Gen. Petraeus and his family for over five years." Kelley said in a statement Sunday. "We respect his and his family's privacy and want the same for us and our three children."

Earlier this year, around the time that Petraeus and Broadwell were breaking off their affair, Kelley began receiving anonymous emails, which she found so threatening she went to authorities. The FBI traced the messages to Broadwell's computer, where they found other salacious and explicit emails between Broadwell and Petraeus that made it clear to officials that the two were carrying on an affair.

An official told ABC News the FBI uncovered "hundreds if not thousands of emails between Petraeus and Broadwell," many of them salacious in nature.

ABC News' Martha Raddatz, Sarah Parnass and the Associated Press contributed to this report.

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‘Skyfall’ brings record Bond debut of $88.4M

LOS ANGELES (AP) — James Bond is cashing in at the box office.

“Skyfall,” the 23rd film featuring the British super-spy, pulled in a franchise-record $ 88.4 million in its U.S. debut, bringing its worldwide total to more than $ 500 million since it began rolling out overseas in late October.

The top 20 movies at U.S. and Canadian theaters Friday through Sunday, followed by distribution studio, gross, number of theater locations, average receipts per location, total gross and number of weeks in release, as compiled Monday by Hollywood.com are:

1. “Skyfall,” Sony, $ 88,364,714, 3,505 locations, $ 25,211 average, $ 90,564,714, one week.

2. “Wreck-It Ralph,” Disney, $ 33,012,796, 3,752 locations, $ 8,799 average, $ 93,647,405, two weeks.

3. “Flight,” Paramount, $ 14,785,097, 2,047 locations, $ 7,223 average, $ 47,455,396, two weeks.

4. “Argo,” Warner Bros., $ 6,617,229, 2,763 locations, $ 2,395 average, $ 85,583,187, five weeks.

5. “Taken 2,” Fox, $ 4,012,829, 2,487 locations, $ 1,614 average, $ 131,300,000, six weeks.

6. “Cloud Atlas,” Warner Bros., $ 2,658,250, 2,023 locations, $ 1,314 average, $ 22,844,956, three weeks.

7. “The Man With the Iron Fists,” Universal, $ 2,592,705, 1,872 locations, $ 1,385 average, $ 12,821,030, two weeks.

8. “Pitch Perfect,” Universal, $ 2,573,350, 1,391 locations, $ 1,850 average, $ 59,099,993, seven weeks.

9. “Here Comes the Boom,” Sony, $ 2,522,790, 2,044 locations, $ 1,234 average, $ 39,033,885, five weeks.

10. “Hotel Transylvania,” Sony, $ 2,400,226, 2,566 locations, $ 935 average, $ 140,954,208, seven weeks.

11. “Paranormal Activity 4,” Paramount, $ 1,980,033, 2,348 locations, $ 843 average, $ 52,600,612, four weeks.

12. “Sinister,” Summit, $ 1,524,448, 1,554 locations, $ 981 average, $ 46,578,686, five weeks.

13. “Silent Hill: Revelation,” Open Road Films, $ 1,300,137, 1,902 locations, $ 684 average, $ 16,383,406, three weeks.

14. “The Perks of Being a Wallflower,” Summit, $ 1,132,924, 607 locations, $ 1,866 average, $ 14,614,770, eight weeks.

15. “Lincoln,” Disney, $ 944,308, 11 locations, $ 85,846 average, $ 944,308, one week.

16. “Alex Cross,” Summit, $ 911,973, 1,090 locations, $ 837 average, $ 24,603,042, four weeks.

17. “Fun Size,” Paramount, $ 757,223, 1,301 locations, $ 582 average, $ 8,800,336, three weeks.

18. “Looper,” Sony, $ 582,150, 491 locations, $ 1,186 average, $ 64,669,383, seven weeks.

19. “The Sessions,” Fox, $ 545,550, 128 locations, $ 4,262 average, $ 1,655,222, four weeks.

20. “Seven Psychopaths,” CBS Films, $ 404,812, 356 locations, $ 1,137 average, $ 14,098,469, five weeks.

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Universal and Focus are owned by NBC Universal, a unit of Comcast Corp.; Sony, Columbia, Sony Screen Gems and Sony Pictures Classics are units of Sony Corp.; Paramount is owned by Viacom Inc.; Disney, Pixar and Marvel are owned by The Walt Disney Co.; Miramax is owned by Filmyard Holdings LLC; 20th Century Fox and Fox Searchlight are owned by News Corp.; Warner Bros. and New Line are units of Time Warner Inc.; MGM is owned by a group of former creditors including Highland Capital, Anchorage Advisors and Carl Icahn; Lionsgate is owned by Lions Gate Entertainment Corp.; IFC is owned by AMC Networks Inc.; Rogue is owned by Relativity Media LLC.

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General investigated for emails to Petraeus friend

PERTH, Australia (AP) — In a new twist to the Gen. David Petraeus sex scandal, the Pentagon said Tuesday that the top American commander in Afghanistan, Gen. John Allen, is under investigation for alleged “inappropriate communications” with a woman who is said to have received threatening emails from Paula Broadwell, the woman with whom Petraeus had an extramarital affair.

Defense Secretary Leon Panetta said in a written statement issued to reporters aboard his aircraft, en route from Honolulu to Perth, Australia, that the FBI referred the matter to the Pentagon on Sunday.

Panetta said that he ordered a Pentagon investigation of Allen on Monday.

A senior defense official traveling with Panetta said Allen’s communications were with Jill Kelley, who has been described as an unpaid social liaison at MacDill Air Force Base, Fla., which is headquarters to the U.S. Central Command. She is not a U.S. government employee.

Kelley is said to have received threatening emails from Broadwell, who is Petraeus’ biographer and who had an extramarital affair with Petraeus that reportedly began after he became CIA director in September 2011.

Petraeus resigned as CIA director on Friday.

Allen, a four-star Marine general, succeeded Petraeus as the top American commander in Afghanistan in July 2011.

The senior official, who discussed the matter only on condition of anonymity because it is under investigation, said Panetta believed it was prudent to launch a Pentagon investigation, although the official would not explain the nature of Allen’s problematic communications.

The official said 20,000 to 30,000 pages of emails and other documents from Allen’s communications with Kelley between 2010 and 2012 are under review. He would not say whether they involved sexual matters or whether they are thought to include unauthorized disclosures of classified information. He said he did not know whether Petraeus is mentioned in the emails.

“Gen. Allen disputes that he has engaged in any wrongdoing in this matter,” the official said. He said Allen currently is in Washington.

Panetta said that while the matter is being investigated by the Defense Department Inspector General, Allen will remain in his post as commander of the International Security Assistance Force, based in Kabul. He praised Allen as having been instrumental in making progress in the war.

The FBI’s decision to refer the Allen matter to the Pentagon rather than keep it itself, combined with Panetta’s decision to allow Allen to continue as Afghanistan commander without a suspension, suggested strongly that officials viewed whatever happened as a possible infraction of military rules rather than a violation of federal criminal law.

Allen was Deputy Commander of Central Command, based in Tampa, prior to taking over in Afghanistan. He also is a veteran of the Iraq war.

In the meantime, Panetta said, Allen’s nomination to be the next commander of U.S. European Command and the commander of NATO forces in Europe has been put on hold “until the relevant facts are determined.” He had been expected to take that new post in early 2013, if confirmed by the Senate, as had been widely expected.

Panetta said President Barack Obama was consulted and agreed that Allen’s nomination should be put on hold. Allen was to testify at his confirmation hearing before the Senate Armed Services Committee on Thursday. Panetta said he asked committee leaders to delay that hearing.

NATO officials had no comment about the delay in Allen’s appointment.

“We have seen Secretary Panetta‘s statement,” NATO spokeswoman Carmen Romero said in Brussels. “It is a U.S. investigation.”

Panetta also said he wants the Senate Armed Services Committee to act promptly on Obama’s nomination of Gen. Joseph Dunford to succeed Allen as commander in Afghanistan. That nomination was made several weeks ago. Dunford’s hearing is also scheduled for Thursday.

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Associated Press writer Slobodan Lekic in Kabul, Afghanistan, contributed to this report.

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