Get the very best restaurants and nightspots right at your fingertips with the all new Zagat
It's been a while since Google did anything with the Zagat franchise they purchased back in 2011, but if you're a fan of the crowd-sourced restaurant rating application genre, you'll likely love what they've done with it. First off, everything is now 100-percent free, and a whole lot of people love free. Mostly though, it's the new modern look and feel they've created in their Android and iOS apps and the website.
Bright, cheery and card-based, it still ties in to services like Google+ and Google Maps to keep you informed about the best places to get your grub on. With curated lists like Restaurants with the Best Food in Washington, D.C. (Obelisk in DuPont Circle has the best Italian west of Roma -- no lie) you'll have access to trusted opinions and ratings.
Zagat still only serves a handful of cities (Austin, Boston, Chicago, LA, NYC, Philly, San Francisco and DC) but if you're a local or plan on traveling, you should give this one a spin. Your stomach will thank you.
Office on Xbox, tons of people with 23" or 27" touchscreens...
Touchscreens for essentially desktops is not a good idea for 99% of people. It just isn't practical or useful (I have a 23" touchscreen). Xbox, like a phone, is for consumption, not creation. If the browser is not held back on the One, I guess you could use office web apps on it but I can't even begin to imagine someone doing that. Also, 6" phones will never be the norm. Most people don't want phablets. Also, the guy said PC and ultrabooks are dead (I assume he meant desktops and laptops). This is completely wrong.
BLUE COLLAR, GOLD SWAGGER! Go Pacers! Good season but you can't win them all!
Cross-Platform Junkie: Lumia 920, Lumia 710, Lenovo Yoga 11s, BlackBerry Z10, 2 Apple TVs, Nexus 7, Kindle Fire HD, Acer C7 Chromebook, ChromeCast, IdeaPad Y560P, AMD A6 based HTPC, Surface RT, i5/7970 based gaming desktop. Like my answers? Tell Dave Blake I am the best Ambassador! I don't get anything btw...
Washington?s recent compromise on interest rates for student loans is a good sign as far as political compromise goes.
But the compromise itself doesn?t really do anything about the larger problem of college affordability. College costs are going up, and there is less incentive for institutions of higher learning to control costs as long as state governments and the federal government are picking up part of the tab.
So what happens? Every year, students have to borrow more, apply for more grants (ones made mostly by the taxpayers), and pay more.
The student-loan interest rate mostly affects graduates. Compromising on the rate won?t help make college more affordable. And Congress is really just postponing higher interest rates. This won?t help students in the long run.
The proposed compromise in Congress would set the rate next year on subsidized Stafford loans at 3.85 percent. Caps would also be put on loans to undergraduates (8.25 percent), graduate students (9.5 percent) and parents (10.5 percent).
The rates doubled July 1 after Congress could not initially agree on new rates. Democrats want lower rates and Republicans want them tied to market rates.
Generally, both Republicans and Democrats praised the deal. No side wants to look like it supports making college unaffordable.
But if tuition and living costs continue to rise, college will be put out of reach for more students.
Perhaps more students should be looking at public colleges and universities for higher education. The costs tend to be lower. In Florida, tuition rates are among the lowest in the nation. The average cost of a bachelor?s degree from a Florida public college is $13,264.
Yet even graduates of more affordable public colleges and universities can leave school loaded with debt. Other costs add significantly to the bill.
The University of Florida, for example, estimates housing and food cost $9,500 a year for an undergraduate student living off-campus. With costs like those, we can expect some students will cancel plans to attend college.
On the other extreme, we can also expect student-loan debt to weigh down the economy. The nation?s student-loan debt is approaching $1 trillion, and has surpassed what Americans owe on automobile loans, according to the Washington Post.
It isn?t unusual for some students to finish college owing $100,000 or more. Many college graduates may postpone buying a house for a decade because of student-loan debt. There are already indications that student debt is becoming a drag on the economy.
So what have our leaders done about it? Very little.
Florida, however, has some high-profile leaders who are stressing college affordability. Gov. Rick Scott has pushed the 28 schools in the Florida College System to offer bachelor?s degrees that cost no more than $10,000 through four years. Scott also pushed successfully to get the state?s public colleges and universities to keep a lid on fees, which raise costs in a stealthy manner. Constant tuition and fee increases make Florida?s college system less affordable.
The nation and its leaders need to take a deeper look at the impact of rising tuition. We must recognize that lowering interest costs on student-loan debt isn?t a long-term solution.
(Reuters) - Of all the legal maneuvers so far in Detroit's bankruptcy case by unions or the city's emergency manager, the one that may have the most impact was when the judge decided to name a mediator.
In a July 23 filing in U.S. Bankruptcy Court, Judge Steven Rhodes said he would appoint another federal judge, Gerald Rosen, as a mediator.
A mediator would be an authoritative voice for compromise in a contentious, messy case, the biggest-ever municipal bankruptcy filing in U.S. history. Detroit, which filed on July 23, has more than $18 billion in debt and 100,000 creditors ranging from retired city workers to Wall Street bond investors.
"I think that's going to be the key move in the case, in terms of getting it toward a solution," Christopher Klein, a bankruptcy judge in Sacramento, California, said. Klein, who is overseeing the bankruptcy of the town of Stockton, spoke last week on a panel organized by the American Bankruptcy Institute.
Rosen, a Republican, is chief district judge of the U.S. District Court for the Eastern District of Michigan. With a long career in Michigan politics and as a member of the conservative-libertarian Federalist Society, he brings a unique perspective to a case that touches on the subjects of states rights and property rights.
Rhodes in his court filing deemed a mediator "necessary and appropriate" but did not specify which issues he feels should be mediated. He has scheduled a hearing on his proposal for Friday.
With Rhodes yet to lay out how mediation will be used, Rosen's role is unclear. He could be asked to help broker a deal resolving the initial objections to Detroit's filing under Chapter 9 of the U.S. Bankruptcy Code, which governs municipal cases. Alternately, his services could be reserved for the more substantive fights over pay back.
COMPLEX ISSUES
Retirees have turned to Michigan state court to try to block Detroit's U.S. Bankruptcy Court filing, saying the state constitution protects their pensions. Creditors have also argued that Detroit Emergency Manager Kevyn Orr failed to negotiate with them in good faith to try to avoid the bankruptcy filing.
On Saturday, Michigan Attorney General Bill Schuette, a Republican, said he would defend retirees who risk losing public pensions because of Detroit's bankruptcy. This put him at odds with Emergency Manager Orr, who was appointed by Governor Rick Snyder, a fellow Republican.
But legal experts say that, ultimately, the case is likely to be resolved in bankruptcy court.
If that happens, a mediator will have a disproportionate impact.
Bankruptcy judges have much less power in Chapter 9 municipal bankruptcies than they do in corporate bankruptcies filed under Chapter 11 of the U.S. Bankruptcy Code. For instance, a judge in Chapter 9 cannot remove municipal officials or tell cities what to do with their property.
A mediator in Chapter 9 bankruptcies plays a central role, acting in settlement talks behind closed doors, unifying disparate creditors and advising them on the realities of the law.
Marc Levinson, a partner at Orrick Herrington & Sutcliffe who represents Stockton, California, in its bankruptcy, said municipal bankruptcies feature less-sophisticated creditors who can benefit from a mediator to walk them through the process.
A mediator can help discourage extreme positions and help bitter adversaries find common ground, said James Spiotto, a Chapter 9 expert and bankruptcy lawyer at Chapman & Cutler.
"It's a reality test," Spiotto said. "Are they in the zone of reality, or do they have no real basis for what they're saying?"
CANDIDATE-TURNED-JUDGE
Rosen was a partner at Detroit-based law firm Miller Canfield in 1990, when President George H.W. Bush named him to the federal bench.
In the 1970s, Rosen was a legislative assistant to Senator Robert Griffin, a Michigan Republican, then ran for Congress in 1982, losing to Democrat Sandy Levin. He has served on the board of the Michigan chapter of the Federalist Society, which emphasizes states' rights and strict adherence to the original meaning of the U.S. Constitution.
Some of the most critical disputes in Detroit's case involve states' rights, namely whether Michigan's state constitution allows the city to cut the pensions of its retirees. But by the time the mediation comes to Rosen, any question of states rights may already have been decided. The case is also subject to Chapter 9 of the U.S. Bankruptcy Code.
"Reality trumps policy, reality should trump politics, and sometimes reality even trumps the law," said Patrick Darby of Bradley Arant Boult Cummings, who represents Jefferson County, Alabama, in its Chapter 9 bankruptcy. "And the reality in Detroit is, there's not enough money."
USE HIM WISELY
According to Darby, mediation works best when there is a clear issue and a limited number of parties.
"When there are two positions on a continuum, the mediator can help find middle ground," he said.
Mediation has had mixed results in Chapter 9. A mediator was unable to help the city of Vallejo, California, reach new labor terms with two of its unions. In Stockton, California, mediation sessions prior to the city's bankruptcy filing helped settle some labor disputes, while other issues remain in mediation.
Sessions typically start with parties together in a conference room presenting their sides, then splitting off into separate rooms, with the mediator shuttling between conferences with each side. It is less formal than court hearings -- while mediators are often judges, they don't wear robes, Spiotto said.
"Guys are usually in shirt sleeves," he said.
Mediators try to relate openly and honestly to parties.
"They say, 'I'm a federal judge, and here's how I think your argument is going to fare in court,'" Darby said.
It Detroit's case, with many creditors battling over a limited amount of money, the process is not so cut-and-dried.
"The best mediator is still going to find it extremely difficult to broker a settlement," Darby said.
(Reporting by Nick Brown; Editing by Eddie Evans and David Gregorio)
MIAMI (Reuters) - Miami police on Sunday searched for a motive for a shooting rampage in which six people were killed by a gunman who set his apartment on fire before shooting several neighbors and taking others hostage.
The police said they were investigating reports that the man, Pedro Alberto Vargas, 42, was in the process of being evicted and had prior disputes with the managers of the building.
The owner of the 90-unit apartment building was immediately available for comment.
More than 100 police, including SWAT teams, stormed an apartment in Hialeah, a suburb of Miami, in a pre-dawn raid on Saturday, killing Vargas and rescuing two of the hostages.
"When we found him, he still had plenty of live rounds of ammunition," Hialeah Police spokesman Carl Zogby told reporters. "This was an irrational act and many times there is no rational explanation."
The weapon used in the incident, a 9-millimeter Glock handgun, was purchased legally in 2010, Zogby said.
Vargas, who arrived in the United States from Cuba in 1997, was described as a part-time graphic artist who kept largely to himself and cared for his elderly mother. He became a U.S. citizen in 2004, according to El Nuevo Herald, south Florida's main Spanish-language newspaper.
He graduated from Miami Dade College with a degree in graphic design. There were no pending civil or criminal cases filed against him in Miami-Dade County courts.
Among the victims were an elderly couple who were the building's managers and four neighbors, including a 17-year-old girl who police say was shot while trying to hide in a bathtub.
Vargas also fired 10 to 20 shots into the street, killing a man who was walking home with his 9-year-old son whom he had just picked up from boxing practice, police said.
It was the worst Miami area shooting since 1982, when 51-year-old Carl Robert Brown killed nine and wounded three others with a pump-action shotgun after a dispute over a $20 lawnmower repair.
Vargas held a permit to carry a concealed weapon. Police gave no information on where he bought the gun or details from the two-page questionnaire on the permit's application. The police said he had no military background.
According to El Nuevo Herald, neighbors knew little of the man other than that he exercised often and was regularly seen wearing gym shorts and running shoes. Neighbors say he regularly took his 83-year-old mother to doctor's appointments.
The shooting started after Vargas set fire to his apartment as well as a large amount of cash. Vargas' mother told police it was $10,000 drawn from his savings account, though the amount remains unconfirmed.
"Much if not all was burned," Zogby said.
The tragedy in Hialeah was the latest in a string of mass shootings in the U.S. including Newtown, Connecticut, where a gunman killed 26 people including 20 young children at Sandy Hook Elementary in December.
The non-profit organization Sandy Hook Promise, formed by community members in Newtown, issued a statement on the Hialeah incident.
"Our hearts are broken," the statement said. "Our spirit is not. Sending prayers and condolences to the victims and families of the Hialeah, Florida mass shooting. Another tragedy that invites us all to reflect on what individual and collective changes we can make as a nation to save lives."
(Additional reporting by David Adams.; Editing by Eric Johnson, David Storey, Mary Wisniewski and Diane Craft)
It?s been a positive past few days for Facebook. The world?s most popular social networking site announced an impressive set of results for Q2 2013?which were well-received by investors, particularly its spike in usage and revenue from mobile.
Facebook passed 819?million mobile monthly active users during the period, which collectively accounted for 41 percent of its total ad revenue,?or $656?million. In conjunction with that, revenue from Asia ? where mobile devices are particularly prevalent for Internet access ? grew nearly 25 percent quarter-on-quarter to account for a record high of $247 million.
Asia is Facebook?s largest region for users, and its latest revenue figure isn?t far from being double the $135 million that Facebook pulled in from the continent one year ago. As Tech In Asia notes, Asia is surely the key growth region for the company, in terms of new signups, increased engagement and more advertising dollars.
Aiming to connect the world via Facebook
Co-founder and CEO Mark Zuckerberg has never been shy to admit his goal is to connect the planet through the service that he created in his dorm at Harvard. Over the past two years, Facebook has consistently grown its user base ??adding 45-50 million users each quarter since Q3 2011 ? which has led some?to speculate that it could add billions more users to the 1.15 billion monthly active users?that it has today.
Facebook?s growth to such a figure is impossible to predict, however, given the way technology and habits rapidly evolve; but one thing seems increasingly certain: Facebook will never crack China.
The company?s IPO filing from February 2012 admitted China is a ?complex? market that it is struggling to find a compromise for, but neither Zuckerberg nor Facebook have said much about the issue since then. Yet, market developments over the past year have made any chance of Facebook finding success in China remote.
Already too late in China
The growth of WeChat, a mobile messaging client run by Internet giant Tencent, has revolutionized the way the average smartphone owner in China communicates with friends, family and even strangers.
In the past we?ve mused over whether Facebook could comply with censors in China ? it is among a number of Western services blocked by the Chinese government; any unblocking would be contingent upon it agreeing to censor content, the same issue would apply if it acquired a firm there ? or whether the culture of Weibo, China?s equivalent of Twitter which has beaten out domestic Facebook clones, means there is little demand for a Facebook-like user experience ? but Tencent?s success with WeChat represents an even greater question mark: if all these questions were answered, is there even room for Facebook?
WeChat has 195 million month active users (MAU) which makes it the world?s second most popular messaging app behind WhatsApp (250 MAU), and ahead of the likes of Line, Kakao Talk, Tango, Viber and others.
WhatsApp doesn?t provide a lot of figures about its business, but details from app stores and reports suggest that its user base is widely spread worldwide. In comparison, just 70 million of WeChat?s near-400 million registered users are based outside of China.
That stat illustrates just how colossal a force WeChat is inside China and Chinese consumer culture.
The service is a smartphone-only messaging app, but it sits squarely in the space that Facebook targets. That?s to say that it is used to message friends daily (using free text chat, voice/video calls), it has location-based services and includes profiles and a social network-style feature that lets users share moments with friends.
It has also attracted media and brands ? including global names like Nike, Starbucks and others ? which can interact with users through the service. WeChat is widely-expected to introduce mobile payments and a social games service to begin monetizing its large following of users.
If that sounds familiar, it?s reminiscent of how Facebook grew its service for PCs, and they are key areas it is aiming to develop to better suit the increasing number for smartphone and tablet users.
All in all, WeChat is the dominant mobile social network in the world?s largest smartphone market. Every day that Facebook is not in China, WeChat?s presence among users, advertisers and even more traditional foes, like (it seems) mobile operators, becomes stronger.
WeChat pushing out overseas
WeChat is expected to pass 400 million registered users within the next few months and it is already accelerating its overseas presence. The service added 20 million users outside of China in the last two months, and a new global advertising campaign ? fronted by football star Lionel Messi ? is likely to see its presence in markets like Southeast Asia, Latin America, Africa and Europe surge.
The company is also said to be planning to open a US office?to ramp up its fight against WhatsApp, Facebook and other mobile messaging and social services on their own turf.
As WeChat furthers its global presence, its hold on China only increases. While Facebook itself has big decisions to make (or hold off making) about China and censorship, the chances of it ever ?connecting? the country ? which Mark Zuckerberg is said to aspire to do ? are fading since another service is already busy doing that.
The counter-argument may be that WeChat is growing a market that Facebook could take over ? in the same way that the likes of Friendster, Myspace, Japan?s Mixi and others helped create the initial wave of social networks which Facebook came to dominate ? but Tencent has the resources, experience and local presence to fortify its position. It?is a billion dollar Internet company?with a pedigree of instant messenger services in China, such as its?Skype-like QQ?service for desktops, and key domestic relationships.
The real question is what effect the mobile-optimized WeChat service, complete with video calls, gaming and more, can have on Facebook?s own business worldwide. Its dominance will be hard to dethrone ? certainly the odds of a non-Chinese company doing so are remote.
If ever a man defined "rock 'n' roll," it would be Mick Jagger. More than almost any performer of the modern age, Jagger embodies all things rock, for good and ill: He's got the swagger, the pipes, the tunes, the attitude, the lifestyle, the drugs, the rivalry (with Keith Richards), the semi-successful movie career, the iconic status across generations. And as of Friday, he turns 70. So in honor of the birthday boy, we look back at some of his most memorable moments ... because nobody has moves quite like Jagger.
Performing on"The Michael Douglas Show" The band had only been together for a couple of years when they gave one of their first U.S. TV performances. But check out Jagger in the video below: All the elements are in place, if slightly toned-down ? Jagger shimmying for the screaming girls, eyeballing the camera lasciviously, and giving every line his all.
Racial, sexual provocateur When he was 35, Jagger sat down for a 1978 TODAY interview in and talked about controversy surrounding The Rolling Stones' "Some Girls" album, noting that the band's next release would be even "more racist and sexist," adding that being successful has made him feel "useless." Fortunately, in the years since Jagger seems to have either reformed his worldviews or learned to keep it out of the press.
Tears off Tina Turner's skirt, mid-song at Live Aid '85 For those who don't remember this moment, Turner and Jagger each tried to out-strut one another during the famous benefit concert, during which they performed "State of Shock" and "It's Only Rock 'N' Roll." It was a last-minute decision to collaborate; reportedly Turner had lyrics to the song written on her arm. What's not in dispute was the very Jagger-like surprise move he pulled on Turner, undoing her leather skirt during their second tune. He had the chutzpah, she had the legs, and they made this early "wardrobe malfunction" work as only they could.
"Mick Dumps Everyone For Bette!!" "Beast of Burden" started out life as the second single from the Rolling Stones' 1981 "Some Girls" album and hit the Top 10, but when Bette Midler got her hands on the tune in 1983, Jagger just had to join in. The ensuing music video for her take on the song hilariously features the pair as a romantic couple, with Jagger starting to put one foot out the door.
Hosting "Saturday Night Live" Jagger holds the titles of both oldest host and oldest musical performer on the long-running NBC variety show "Saturday Night Live" (he was nearly 69 at the time) but he can hold his own with whoever he's paired up alongside ... even if it requires him to put on a Southern Californian accent to do it.
Mick Jagger, Thespian Over the years, Jagger's onstage charisma has never translated as forcefully onto the big screen, but that doesn't mean he hasn't given it a good try, in films like 1970's "Ned Kelly," an early (aborted) version of Werner Herzog's 1979 film "Fitzcarraldo," and 2001's "The Man from Elysian Fields." But for sheer all-out bad guy weirdness, it's hard to top his role as a mercenary who kidnaps Emilo Estevez in 1992's "Freejack." (Which, by the way, supposedly takes place in 2009. Oh, well.)
Jagger and Bowie Okay, believe what you like about Angela Bowie's claim that she once caught her ex-husband David Bowie and Jagger in bed together, unclothed. Whatever these two divos may have had together is their business ? but for those who still doubt it ever happened, can you really question there's some kind serious chemistry at work in their 1985 remake of Martha and the Vandellas' "Dancing In the Street"? We can't.
"Moves Like Jagger" After 50 years in the business, and as of Friday aged 70, Mick Jagger has been around long enough to warrant his own tribute song ? which Maroon 5 happily obliged with in 2011. Via archival footage, Jagger was of course present in the video (and later in an interview called the song "flattering"). Here's to another 70 great, move-filled years, Mick!
Authorities at the scene of shooting at an apartment building in Hialeah, Fla.
HIALEAH, Fla. ?? A man set fire to his South Florida apartment, killed six people, and held another two hostage at gunpoint for three hours before a SWAT team stormed the complex and fatally shot him Saturday, according to police and witness accounts.
Pedro Vargas, a 43-year-old resident of the apartment building, set a combustible liquid on fire to start the blaze Friday evening, police spokesman Carl Zogby said.
The building manager and his wife noticed smoke and ran to the apartment. Vergas came out and shot several times, killing both of them, according to the police account.
Vargas then went to his fourth-story balcony and fired 10 to 20 shots in the street, killing a man who was parking a car outside, Zogby said.
Then, Vargas went down to the third floor, kicked the door in on another apartment and killed a man, his wife and their teen daughter.
Vargas was running through the building, firing at random with a 9 mm pistol and eluding police. Police said he forced his way into an apartment and took two people hostage at gunpoint.
Ester Lazcano lives two doors down from where the shooting began and said she was in the shower when she heard the first shots, then there were at least a dozen more.
"I felt the shots," she said.
Miriam Valdes, 70, lives on the building's top floor ? one floor above where the shooting began. She said she heard gunfire and later saw smoke and what smelled like burned plastic entering her apartment, and ran in fear to the unit across the hall.
A crisis team was able to briefly establish communication with Vargas. Sgt. Eddie Rodriguez said negotiators and a SWAT team tried talking with him from the other side of the door of the unit where he held the hostages.
Valdes said she heard about eight officers talking with him as she stayed holed up at the neighboring apartment. She said officers told him to "let these people out."
"We're going to help you," she said they told him.
She said the gunman first asked for his girlfriend and then his mother but refused to cooperate.
Rodriguez said the talks eventually "just fell apart." Officers stormed the building, fatally shooting the gunman in an exchange of gunfire.
"They made the decision to go in there and save and rescue the hostages," Rodriguez said. Both hostages survived.
Neighbors said the shooter lived in the building with his mother.
"He was a good son," Lazcano said. "He'd take her in the morning to run errands" and took her to doctor appointments.
But Valdes said he was known as a difficult person who sometimes got into fights and yelled at his mother.
"He was a very abusive person," she said. "He didn't have any friends there."
Zulima Niebles said police told her that three of her family members were among the victims. She said her sister Merly Sophia Niebles, her sister's husband, and her sister's teen daughter Priscila Perez were all shot and killed.
Zulima Niebles' husband, Agustin Hernandez, was moving the family's things out of the apartment building and into his car Saturday. Among them were several photos, one showing the teen smiling in a red graduation gown, another of his sister-in-law in a white dress and pearls.
Hernandez said his sister-in-law's husband was a friend of the building manager.
Marcela Chavarri, director of the American Christian School, said Priscila Perez was about to enter her senior year at the school.
"She was a lovely girl," Chavarri said through tears. "She was always happy and helping her classmates."
In Hialeah ? a suburb of about 230,000 residents, about three-quarters of whom are Cuban or Cuban-American ? the street in the quiet, apartment-building-lined neighborhood was still blocked by tape Saturday afternoon.
The building where the standoff occurred is an aging, beige structure with an open terrace in the middle. The apartment where neighbors said the shooting started was charred, the door and ceiling immediately outside burned black.
The building across the street where the man was shot is called Casa Royal, or Royal House in English.
Source: www.myfinances.co.uk --- Friday, July 26, 2013 The Church of England has faced an embarrassing blow after it emerged that it may have indirectly invested in online lender Wonga. ...
BAGHDAD (AP) ? Emboldened militants in Iraq set up their own checkpoint to kill drivers and bombed crowded cafes Thursday in the deadliest of a series of attacks that killed at least 42 people, authorities said.
More than 550 people have been killed in violent attacks so far this month, according to an Associated Press count, as violence continues during the Muslim holy month of Ramadan. The speaker of Iraqi parliament even has acknowledged that insecurity in the nation likely will get worse after a massive al-Qaida-claimed prison break freed hundreds of inmates.
The deadliest attack Thursday happened when a bomb exploded inside a crowded cafe north of Baghdad, killing 16 diners and wounded 20 others.
Iraqi police said that the blast targeted Noufel cafe near the town of Muqdadiyah, about 90 kilometers (60 miles) north of Baghdad.
Ahmed Ibrahim, a government employee, was shopping near the targeted cafe when he heard a thunderous explosion.
"Everybody rushed to the explosion site and saw charred bodies that were thrown outside the cafe because of the powerful explosion," he said. "The scene was horrible."
An hour later, a bomb went off inside another cafe near Baghdad, killing two people and wounding six, authorities said. Hospital officials confirmed the casualty figures.
During Ramadan, cafes in Iraq become quite crowded as people gather there to break the daily fast. Extremists have targeted crowded cafes this year.
Militants have grown bolder in their attacks as well. Earlier Thursday, insurgents outside the village of Sarha launched mortar rounds at a nearby military base and bombed a communication tower to distract security forces. Then they quickly set up a fake checkpoint on a nearby highway to stop passing vehicles, said Col. Hussein Ali Rasheed, the police chief in nearby Tuz Khormato, about 200 kilometers (125 miles) north of Baghdad.
The corpses of 14 drivers and passengers in a convoy of trucks caught at the checkpoint, all of them Shiites, were later found, each killed by gunshot wounds to the head, Rasheed said.
In the northern city of Beiji, 250 kilometers (155 miles) north of Baghdad, militants shot and killed three off-duty soldiers as they were leaving a restaurant, provincial health official Raed Ibrahim said. The soldiers were on their way to Baghdad from Mosul.
And in the city of Kirkuk, a parked car bomb targeted a passing police patrol on Thursday morning, critically wounding six policemen, police Col. Salah Abdul-Qadir said. Kirkuk is 290 kilometers (180 miles) north of Baghdad.
Also, police said gunmen using pistols fitted with silencers shot and killed four people, including two street cleaners, in three separate incidents in Baghdad. Thursday night, a bomb exploded during a small wedding party held in a house in Baghdad's Amiriyah neighborhood, killing three people and wounding 16 others, including some women and children, police and hospital officials said.
All officials spoke on condition of anonymity as they were not authorized to speak to journalists.
The attacks happened amid the backdrop of the Sunday night attack on the notorious Abu Ghraib prison and another lock-up in Taji, both on the outskirts of Baghdad. Dozens of people, mainly members of the security forces and inmates, were killed in the attacks.
Parliament speaker Osama al-Nujaifi told journalists Thursday that the latest reports indicate that more than 500 prisoners escaped ? a figure similar to what other Iraqi officials have provided. He said a parliamentary committee is investigating what happened.
"The situation is grave," said al-Nujaifi, a Sunni who frequently has criticized the Shiite prime minister, Nouri al-Maliki. "We don't know who they are and how dangerous they are, but this situation will be reflected negatively on the security situation."
Al-Qaida's Iraq branch claimed responsibility for the prison attacks Tuesday. Interpol issued its security alert Wednesday to warn counties in the region about the fugitives, calling the breakouts "a major threat to global security."
Many of the escaped prisoners were senior members of al-Qaida in Iraq, including some who were facing the death penalty, according to Interpol.
Violence in Iraq has reached levels not seen since 2008, fueling worries of a return to the widespread sectarian killing that pushed the country to the brink of civil war after the 2003 U.S.-led invasion. More than 3,000 people have been killed since April.
Ramadan this year is shaping up to be the bloodiest since 2007, with more than 350 Iraqis killed since the holy month started on July 10, according to an AP count.
___
Associated Press writers Adam Schreck and Sameer N. Yacoub contributed to this report.
Hey hey hey, it's the summer's hottest viral video/mashup/lip dub/cover song, Robin Thicke's "Blurred Lines." You know the drill: Last summer, it was Carly Rae Jepsen's "Call Me Maybe" that was covered by everyone from the Olympic swim team to Cookie Monster. (We rounded up the different versions in this post.)
Getty Images; EPA
Bill Cosby, Kermit the Frog and Alan Thicke all star in versions of Thicke's son Robin's hit, "Blurred Lines."
This year, the hot song is a bit more controversial than Jepsen's blockbuster -- some critics dubbed Thicke's song "rapey" for such lyrics as "I know you want it ... but you're a good girl." (Thicke says those charges are hogwash, by the way.) And the video features topless women holding goats. (We don't know.)
The controversy hasn't stopped everyone with ears from throwing together a fresh take on the "Blurred" phenomenon, often featuring famous people. From presidents to Muppets to Robin Thicke's own actor dad, everybody's blurring the lines. Here are a few of our favorites. (Note: Language is sometimes explicit, images are sometimes risque.)
'Blurring Pains' It was inevitable. Robin Thicke's song meets his dad Alan's iconic 1980s-90s family sitcom, "Growing Pains." Retro still rules.
'Cosby Show' Speaking of nostalgia, another awesome mashup takes the opening credits from the 1980s "Cosby Show" and shows the Huxtable family dancing to Thicke's hit.
Bill Clinton The former president's romantic reputation makes him a believable parody topic for the sexy song. And current President Barack Obama gets to steal the show with a soulful line of his own.
Kermit the Frog and the Muppets Oh yes, Kermit the Frog is popular with the ladies -- just ask Miss Piggy. He leads the other Muppets in an entertaining romp through Thicke's tune. It's not easy being green, but Kermie nails it.
Vampire Weekend There's no video, just audio, but all the better to highlight this goofy-fun cover by the rock band, who don't always remember Thicke's lyrics.
Mod Carousel Thicke's video was criticized by some for featuring several lovely topless women stalking around while the men remain fully clothed. This risque version, by "boylesque" troupe Mod Carousel, reverses the genders for some equal-opportunity almost-nudity.
Jimmy Kimmel The host of "Jimmy Kimmel Live" showed his own take on the video on his talk show. Let's just say Thicke, Pharrell and his crew of models are not so thrilled to have Kimmel and pal Guillermo trying to nudge their way into the action -- especially when Kimmel gets up close and personal with Thicke's face.
Super Mario Bros. Mario, King Koopa and the whole 1980s video game crew get into a whole weird 8-bit area with this version. Thank you, Mario, but our princess is in another castle.
There are plenty of other versions out there -- including a country-western take and yes, even a kids' version (which substitutes G-rated lyrics like "I know you wanna ... join a Kids' World").
Lines getting too blurry for you? Vote in our poll and pick your favorite version.
After the successful birth of Prince George earlier this week, it's finally time for Kate Middleton and Prince William to head home.
On Wednesday's edition of Live From E!, Arlene Santana, Ken Baker and Marc Malkin discussed the best moments from the royal event as well as what we can expect in the future.
With Melanie Bromley reporting from London, the group also reported Prince Harry and Pippa Middleton were able to finally?meet the baby boy inside?Kensington Palace.
In hopes of having some peace and quiet, the royal family is now heading to Bucklebury where they are expected to meet up with Middleton's family for an extended stay.
NEWS: The royal baby is named! Meet Prince George Alexander Louis of Cambridge
Also on today's show, the panel updated us on Amanda Bynes' 5150 hold. The former Nickelodeon star continues her 72-hour hold after being detained Monday evening for a disturbance in a residential neighborhood.
According to?one eyewitness who spoke with E! News, Bynes had her pant leg on fire after a small blaze was set in a nearby driveway.
PHOTOS: Beware, Amanda has called a lot of people ugly
Finally, could the rumors be true that Gwyneth Paltrow and Chris Martin are renewing their vows?
As their 10-year marriage anniversary approaches this December, reports say the couple will say "I Do" once again in a low-key ceremony.
According to Paltrow's rep, however, the stories are nothing but rumors. Guess we will just have to wait and see what the lovebirds have in store for us later this year.
Be sure to check us out every day at 12:30 p.m. ET/9:30 a.m. PT! And don't forget to follow us on Twitter @LiveFromE and hit us with your questions using the #LiveFromE hashtag.
PHOTOS: Chris and Gwyneth aren't the only celebrity couples we love
Third time's a charm for Rose McGowan! The 39-year-old "Charmed: actress is engaged to artist Davey Detail, her rep confirms to Us Weekly.
PHOTOS: Best celebrity engagement rings
McGowan and Detail began dating last year. Rumors surfaced last week that the couple was engaged after McGowan stepped out wearing a ring on a very important finger on July 17.
PHOTOS: Celebrity weddings 2013
The actress was spotted going for a walk with Detail in West Hollywood wearing a large diamond ring. She paired the new sparkler with a white crop top and ripped jeans.
PHOTOS: 10 best celeb rings
This will be McGowan's first marriage. She was previously engaged to rocker Marilyn Manson for two years before calling it off in 2001, and to director Robert Rodriguez in 2007 before calling it quits in 2009.
INDIANAPOLIS (AP) -- Indiana's Crossroads Classic will be played through at least 2016.
The four schools said Monday that Purdue will face Butler on Dec. 19, 2015, with Indiana taking on Notre Dame in the other game. The Boilermakers and Fighting Irish will square off on Dec. 17, 2016, with Butler and Indiana meeting in the other game. All games will again be played at Bankers Life Fieldhouse.
The doubleheader has become one of the state's biggest regular-season basketball events with all four power conference schools participating - longtime Big Ten members Indiana and Purdue, new ACC member Notre Dame and new Big East member Butler.
It's the second time the schools have announced a two-year extension since the tourney began in 2010.
Copyright 2013 Associated Press. All rights reserved. This material may not be published, broadcast, rewritten, or redistributed.
I wanted to do an auction league but I have never done one before so didnt really want to jump straight $100 league as my first one so I'm going to set up a $25 league. I'll also set up a $25 league with a snake draft as it seemed like there were quite a few people who wanted to join that league but got in too late.
Both leagues will be 12 teams and PPR. I'll hold on paypal. Can accept on stars as well but I dont know how many people that will be an option for. I have held for a few contests over the last few years and everybody was paid up quickly at the end.
So yeah, post in this thread if you are interested and ill pm you my paypal details.
And remember when sending on paypal dont include anything about the league or anything that could link it back to ffb.
MOSCOW (AP) ? Alexei Navalny's energy and charisma propelled him from a lonely role blogging about corruption to wide renown as Russia's leading opposition activist. His projects, including a campaign to run for Moscow mayor, have attracted hordes of volunteers and fundraisers. Now comes a day that looms large for Navalny and the opposition: A court hands down its verdict Thursday in an embezzlement case that could send him to prison for six years.
In the four years since Navalny began blogging about Russia's endemic corruption, the 37-year-old lawyer has become the major figure of Russia's nascent opposition. He spearheaded the wave of massive protest rallies that arose in late 2011, riveting crowds of 100,000 or more. Even as his embezzlement trial proceeded in the provincial city of Kirov, Navalny pushed forward his movement by declaring himself a candidate for this fall's Moscow mayoral election, attracting a wave of eager young volunteers.
He and many observers are sure a conviction is coming in what they describe as a politically motivated case. What seems less certain is the impact: If he goes to prison, it could sap his movement by taking away its galvanizing figure ? or make supporters more determined.
Navalny is charged with heading a group that embezzled 16 million rubles ($500,000) worth of timber from state-owned company Kirovles while he worked as an unpaid adviser to the provincial governor in Kirov in 2009. Although the case is murky, the only question is "whether there will be a conditional sentence on trumped-up charges or a prison sentence on the same trumped-up charges," Navalny told Echo Moskvy radio last week.
Navalny began his rise to prominence by blogging about his investigations into corruption at state-owned companies where he owned shares. Supporters and funding poured in, turning this one-man show into the leader of a team of 14 lawyers and activists. Although state-controlled broadcasters ignored him, he exploited social media and his blog to reach hundreds of thousands.
Navalny's best-known project, the Rospil website, monitors state contracts and appeals to law enforcement agencies to get the dodgy ones annulled. It employs six lawyers who have overturned nearly 130 contracts since 2010, worth 59 billion rubles ($1.8 billion) in taxpayer money. Other Navalny projects rely on crowdsourcing, attracting information about various grievances from potholes on the roads to leaking pipes in apartment blocks.
Navalny has also plumbed property registers abroad to name and shame top officials and lawmakers for owning undeclared foreign assets and holding foreign citizenship. One of them, Vladimir Pekhtin, the head of the ethics commission in the lower house of parliament, resigned in February after Navalny blogged about Pekhtin's luxury property holdings in Miami Beach.
Navalny's investigations have targeted a wide circle of loyalists to President Vladimir Putin ? from members of parliament to state bankers, striking at the core of Putin's "vertical of power" and threatening to discredit the entire system of governance he has built. Lilia Shevtsova, a political analyst at the Carnegie Center in Moscow, said Navalny's anti-corruption campaign has inflicted "painful bites on the system," turning the blogger into a political leader.
Unlike many of his peers in the Russian opposition, Navalny poses a tangible threat to the government because he doesn't only "sign petitions against the bloody regime" but actually does something every day, said Leonid Volkov, head of Navalny's election headquarters.
"Navalny is the only person in Russia who views politics as routine 24/7 work," Volkov said. "Navalny always has something going on. He's always busy."
His Foundation for Fighting Corruption, an umbrella organization for projects, is run by Navalny himself and Vladimir Ashurkov, a U.S.-educated former asset manager who has been the key fundraiser for the foundation. Ashurkov refused to comment on the prospects of Navalny's projects until the verdict is announced. But some of his employees voiced confidence that Navalny's anti-corruption efforts will not be affected by his possible prison sentence.
Lyubov Sobol, a lawyer who has worked for Rospil for two years, is optimistic that she and her colleagues will be able to carry on. Navalny and his team have talked about the possibility of a prison sentence and "different scenarios for development," Sobol said.
"We came to a conclusion that what we do at the Foundation will go on regardless," Sobol said. "All of the employees are independent and know their job well."
At Navalny's election headquarters in central Moscow, dotted with bright pink desks and white chairs, dozens of cheerful volunteers canvass voters by phone and push Navalny's mayoral candidacy on social media. The possibility of prison for their candidate doesn't seem to faze them.
Volunteer Oleg Kozlovsky, 29, said the lawyer's supporters "try to focus on things that we can change" rather than on something "as unpredictable as the weather."
"If Alexei gets a prison sentence, the number of volunteers and supporters will only increase," he said.
But Navalny's conviction could undermine the fund's activities by robbing it of its vocal leader. Imprisonment could also spook potential donors.
"Navalny will carry on with his activities in so far as it's possible in incarceration, but it's impossible to fight corruption out of prison," said Alexei Makarkin of the Moscow-based Center for Political Technologies.
According to Makarkin, potential donators became more cautious bankrolling the opposition since Putin's crackdown on the protest movement last spring, and their fears could get even worse.
"They may have problems with the financing," Makarkin said. "In financing a lot of things are based on personal relations, and Navalny is a charismatic figure, he was able attract investors and donors."
Navalny's name could still be on the ballot on Sept. 8 if he's convicted on Thursday. Authorities will not be able to bar him from running until the guilty verdict comes into effect; that wouldn't happen until the defense has exhausted appeals, a process that could take at least several months.
The protest rallies of 2011 and 2012 were largely peaceful, authorized gatherings, attracting thousands of middle-class Russians who had not been to the largely marginal protests of the past decade. But this may be changing with the Thursday verdict for the central leader of those protests. Navalny's supporters are already planning a rally that evening just outside the Kremlin walls ? despite the fact that authorities refused to give the green light. The Facebook page of the event has more than 6,500 people listed as going.
Campaign volunteer Alexei, a 20-year-old law student, said he has never been to an unsanctioned rally, but would take the risk on Thursday if Navalny is sentenced to prison.
"Moscow authorities left us no choice," said Alexei, who asked that his last name not be used for fear of being expelled from university, something that he saw happen to his friends before.
A guilty verdict for Navalny is "probable and even inevitable," said Shevtsova of Carnegie, but it still has yet to be seen how strong a blow for the opposition movement this will be. "So far, Navalny is not a Boris Yeltsin," Shevtsova said, referring to Russia's first president who rode an unstoppable popular movement to power.
Longer-term consequences of Navalny's convictions could be more dangerous for the Kremlin than unsanctioned protests on the day of the verdict. State-television has vilified Navalny, portraying him as a corrupt rich Muscovite who defrauded an impoverished timber company.
But his imprisonment alone could turn Navalny into a victim of the Kremlin intrigue.
Makarkin said a conviction could give Navalny a new role: "People's martyr sent to jail by corrupt officials."
With ?The Conjuring? looking like a sleeper hit, New Line is already working on bringing a sequel to life.
James Wan?s demonic possession thriller opens Friday in the wake of off-the-charts test screening results and strong reviews. Set in Rhode Island in 1971, the story is based on the work of real-life paranormal investigators Ed and Lorraine Warren ? portrayed by Patrick Wilson and Vera Farmiga. Ron Livingston and Lili Taylor play father and mother of the five Perron girls who were terrorized by the haunted house.
?Horror is very much a part of the DNA of New Line ? ?Nightmare on Elm Street,? ?Friday the 13th,? ?The Rite,? and the ?Final Destination? films,? notes New Line president Toby Emmerich. ?This is as good a horror movie as we?ve ever made?. We think it will have great playability.?
SEE MORE: New Line Counts on ?Conjuring? to Raise Its Lagging B.O. Spirits
Emmerich told Variety that New Line is exploring a potential franchise based on the Warrens? investigations, which also involved cases that wound up as the movies ?The Amityville Horror? and ?The Haunting in Connecticut.? ?We have Lorraine?s permission and support, and we are working on developing another film,? Emmerich said.
The team of Carey Hayes and Chad Hayes, who penned ?The Conjuring,? are on board as writers for the sequel. The brothers interviewed Lorraine Warren extensively as part of developing the script.
Warner Bros. had originally dated ?The Conjuring? for Jan. 25, but decided last fall to move it back to this summer as a result of the test screening results. Producers are Rob Cowan, Peter Safran and Tony DeRosa-Grund.
NEW YORK (AP) ? A teenager from Connecticut who sang songs from popular Broadway hits like "Newsies" and another from California who nailed the sassy tune "Raunchy" from the musical "110 in the Shade" won top honors Monday night at the National High School Musical Theater Awards.
Sarah Lynn Marion, from Fullerton, Calif., was named best actress and Taylor Varga from Newtown, Conn., got the best actor crown at the fifth annual "Glee"-like competition, nicknamed the Jimmy Awards after theater owner James Nederlander.
Both top winners will receive a $10,000 scholarship award, capping a months-long winnowing process that began with 50,000 students from 1,000 schools and ended at the Minskoff Theatre, the long-term home of "The Lion King." This year's contestants come from 20 states.
Marion, who studies at Huntington Beach High School for the Performing Arts and had sung a segment from "Hello, Dolly," absolutely nailed the song "Raunchy," with the appropriate lyric, "Gonna make them other gals turn green."
In her acceptance speech, she thanked her teachers, her parents, her four siblings, her friends and all fellow contestants. "And my first grade teacher who gave me my first role as Jack's mother in 'Jack and the Beanstalk,'" she said.
Varga, who attends Newtown High School, was one of two J. Pierrepont Finches from "How to Succeed in Business Without Really Trying" and delivered a touching "Santa Fe" from "Newsies" for his solo. "I'm a little lost for words," he said, before thanking his family and friends who made the trip from Connecticut.
The 62 teens who made it to New York ? 31 girls and 31 boys ? got a five-day theatrical boot camp at New York University's Tisch School of the Arts, complete with scrambling to learn an opening and closing group number, intense advice on their solo songs, plus a field trip to watch "Annie" on Broadway and dinner at famed theater-district hangout Sardi's.
All 62 performed snippets of the songs that they had sung at regional competitions as part of seven large medleys and then seven finalists ? three boys and four girls ? were asked to sing solos. The final winners were picked from the last seven.
All had to switch from black dresses for the ladies and dark suits for the men at the top of the show into their character costumes for their medleys and then back again. Their performances were backed by a nine-piece orchestra.
The five runners-up, who each receive $2,500, were: Martha Hellerman from Madison, Wis.; Eva Maria Noblezada from Charlotte, N.C.; Jillian Caillouette from Norwich, Conn.; Michael Burrell from Mission Viejo, Calif.; and Austin Crute from Atlanta.
There was a fair amount of overlapping of roles, with two Belles from "Beauty and the Beast," two Miss Adelaides from "Guys and Dolls" and a memorable set of five Bakers from "Into the Woods," who were all thrown on stage to duke it out together.
The irreverent show "Avenue Q" had two representatives, complete with puppets, and there was a tap dancing Billy Crocker from "Anything Goes" and a gun-toting Annie Oakley in "Annie Get Your Gun." Shows ranged from "Chicago" to "Sweeney Todd" to "Les Miserables" and "In the Heights."
During their visit, the teens were tutored one-on-one by theater pros Leslie Odom Jr., Liz Callaway, Michael McElroy and Telly Leung. The judges Monday night included Tony-winning director Scott Ellis, Tony nominee Montego Glover and casting professional Bernie Telsey. One judge was overheard summing up the judging process with one word: "brutal." The hosts were Laura Osnes and Santino Fontana, who co-star in "Rodgers + Hammerstein's Cinderella."
___
Online:
http://www.nhsmta.com
___
Mark Kennedy can be reached at http://twitter.com/KennedyTwits
It's about time: Disrupted internal clocks play role in diseasePublic release date: 1-Jul-2013 [ | E-mail | Share ]
Contact: Megan Fellman fellman@northwestern.edu 847-491-3115 Northwestern University
Study uncovers circadian disruption as risk factor in alcoholic liver disease
Thirty percent of severe alcoholics develop liver disease, but scientists have not been able to explain why only a subset is at risk. A research team from Northwestern University and Rush University Medical Center now has a possible explanation: disrupted sleep and circadian rhythms can push those vulnerable over the edge to disease.
The team studied mice that essentially were experiencing what shift workers or people with jet lag suffer: their internal clocks were out of sync with the natural light-dark cycle. Another group of mice had circadian disruption due to a faulty gene. Both groups were fed a diet without alcohol and next with alcohol, and the team then examined the physiological effects.
The researchers found the combination of circadian rhythm disruption and alcohol is a destructive double hit that can lead to alcoholic liver disease.
The study was published last month by the journal PLOS ONE.
"Circadian disruption appears to be a previously unrecognized risk factor underlying the susceptibility to or development of alcoholic liver disease," said Fred W. Turek, the Charles E. and Emma H. Morrison Professor of Biology at Northwestern's Weinberg College of Arts and Sciences and one of the senior authors of the paper.
"What we and many other investigators are doing is bringing time to medicine for the diagnosis and treatment of disease," Turek said. "We call it circadian medicine, and it will be transformative. Medicine will change a great deal, similar to the way physics changed when Einstein brought time to physics."
A number of years ago, Ali Keshavarzian, M.D., a gastroenterologist at Rush University Medical Center who has worked with and studied patients with gastrointestinal and liver diseases, had a hunch disrupted circadian rhythms could be a contributing factor to the disease.
Keshavarzian had noticed that some patients with inflammatory bowel disease (inflammation in the intestine and/or colon) had flare-ups of symptoms when working nights, but they could control the disease when working the day shift. He sought out Turek, director of Northwestern's Center for Sleep and Circadian Biology, to help investigate the relationship between circadian rhythms and the disease.
The two investigators and their groups first studied the effect of circadian rhythm disruption in an animal model of colitis and noted that disruption of sleep and circadian rhythms (caused by modeling shift work and chronic jet lag in the animals) caused more severe colitis in mice.
Keshavarzian has been studying the effect of "gut leakiness" (the intestinal lining becomes weak and causes dangerous endotoxins to get into the blood stream) to bacterial products in gastrointestinal diseases for two decades. Because the mouse model of colitis is associated with leaky gut, he proposed that disruption of circadian rhythms from shift work could make the intestine more susceptible to leakiness. He wanted to test its effect in an animal model of alcoholic liver disease -- where a subset of alcoholics develop gut leakiness and liver disease -- in order to find out whether shift work is the susceptibility factor that promotes liver injury.
"Non-pathogen-mediated chronic inflammation is a major cause of many chronic diseases common in Western societies and developing countries that have adopted a Western lifestyle," said Keshavarzian, one of the senior authors of the paper. He is director of the Division of Digestive Diseases and the Josephine M. Dyrenforth Chair of Gastroenterology.
Crohn's and ulcerative colitis, Parkinson's disease, diabetes, multiple sclerosis, autoimmune disease and cardiovascular disease are examples of these diseases, to name just a few.
"Recent studies have shown that intestinal bacteria are the primary trigger for this inflammation, and gut leakiness is one of the major causes," Keshavarzian said. "The factor leading to gut leakiness is not known, however. Our study suggests that disruption of circadian rhythms and sleep, which is part of life in industrial societies, can promote it and explain the susceptibility."
In the study, the Northwestern and Rush researchers used two independent approaches, studying both genetic and environmental animal models. The circadian rhythms of one group of mice were disrupted genetically: Each animal had a mutant CLOCK gene, which regulates circadian rhythms. The second group's circadian rhythms were disrupted environmentally: The animals' light-dark cycle was changed periodically, leading to a state similar to chronic jet lag.
Mice in both groups, prior to ingesting alcohol, showed an increase in gut leakiness.
Next, both groups of mice were fed alcohol. After only one week, animals in both groups showed a significant additional increase in gut leakiness, compared to control mice on an alcohol-free diet. At the end of the three-month study, mice in both groups were in the early stages of alcoholic liver disease.
"We have clearly shown that circadian rhythm disruption can trigger gut leakiness, which drives the more severe pathology in the liver," said Keith Summa, a co-first author of the study and an M.D./Ph.D. candidate working in Turek's lab.
"For humans, circadian rhythm disruption typically is environmental, not genetic, so individuals have some control over the behaviors that cause trouble, be it a poor sleep schedule, shift work or exposure to light at night," he said.
Sleep and circadian rhythms are an integral part of biology and should be part of the discussion between medical doctors and their patients, the researchers believe.
"We want to personalize medicine from a time perspective," Turek said. "Our bodies are organized temporally on a 24-hour basis, and this needs to be brought into the equation for understanding health and disease."
###
The paper, titled "Disruption of the Circadian Clock in Mice Increases Intestinal Permeability and Promotes Alcohol-Induced Pathology and Inflammation," is available at http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0067102.
In addition to Turek, Keshavarzian and Summa, other authors of the paper are co-first author Robin M. Voigt, Christopher B. Forsyth, Maliha Shaikh and Yueming Tang, of Rush University Medical Center; Martha Hotz Vitaterna and Kate Cavanaugh, of Northwestern; and Shiwen Song, of the American Society for Clinical Pathology.
[ | E-mail | Share ]
?
AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert! system.
It's about time: Disrupted internal clocks play role in diseasePublic release date: 1-Jul-2013 [ | E-mail | Share ]
Contact: Megan Fellman fellman@northwestern.edu 847-491-3115 Northwestern University
Study uncovers circadian disruption as risk factor in alcoholic liver disease
Thirty percent of severe alcoholics develop liver disease, but scientists have not been able to explain why only a subset is at risk. A research team from Northwestern University and Rush University Medical Center now has a possible explanation: disrupted sleep and circadian rhythms can push those vulnerable over the edge to disease.
The team studied mice that essentially were experiencing what shift workers or people with jet lag suffer: their internal clocks were out of sync with the natural light-dark cycle. Another group of mice had circadian disruption due to a faulty gene. Both groups were fed a diet without alcohol and next with alcohol, and the team then examined the physiological effects.
The researchers found the combination of circadian rhythm disruption and alcohol is a destructive double hit that can lead to alcoholic liver disease.
The study was published last month by the journal PLOS ONE.
"Circadian disruption appears to be a previously unrecognized risk factor underlying the susceptibility to or development of alcoholic liver disease," said Fred W. Turek, the Charles E. and Emma H. Morrison Professor of Biology at Northwestern's Weinberg College of Arts and Sciences and one of the senior authors of the paper.
"What we and many other investigators are doing is bringing time to medicine for the diagnosis and treatment of disease," Turek said. "We call it circadian medicine, and it will be transformative. Medicine will change a great deal, similar to the way physics changed when Einstein brought time to physics."
A number of years ago, Ali Keshavarzian, M.D., a gastroenterologist at Rush University Medical Center who has worked with and studied patients with gastrointestinal and liver diseases, had a hunch disrupted circadian rhythms could be a contributing factor to the disease.
Keshavarzian had noticed that some patients with inflammatory bowel disease (inflammation in the intestine and/or colon) had flare-ups of symptoms when working nights, but they could control the disease when working the day shift. He sought out Turek, director of Northwestern's Center for Sleep and Circadian Biology, to help investigate the relationship between circadian rhythms and the disease.
The two investigators and their groups first studied the effect of circadian rhythm disruption in an animal model of colitis and noted that disruption of sleep and circadian rhythms (caused by modeling shift work and chronic jet lag in the animals) caused more severe colitis in mice.
Keshavarzian has been studying the effect of "gut leakiness" (the intestinal lining becomes weak and causes dangerous endotoxins to get into the blood stream) to bacterial products in gastrointestinal diseases for two decades. Because the mouse model of colitis is associated with leaky gut, he proposed that disruption of circadian rhythms from shift work could make the intestine more susceptible to leakiness. He wanted to test its effect in an animal model of alcoholic liver disease -- where a subset of alcoholics develop gut leakiness and liver disease -- in order to find out whether shift work is the susceptibility factor that promotes liver injury.
"Non-pathogen-mediated chronic inflammation is a major cause of many chronic diseases common in Western societies and developing countries that have adopted a Western lifestyle," said Keshavarzian, one of the senior authors of the paper. He is director of the Division of Digestive Diseases and the Josephine M. Dyrenforth Chair of Gastroenterology.
Crohn's and ulcerative colitis, Parkinson's disease, diabetes, multiple sclerosis, autoimmune disease and cardiovascular disease are examples of these diseases, to name just a few.
"Recent studies have shown that intestinal bacteria are the primary trigger for this inflammation, and gut leakiness is one of the major causes," Keshavarzian said. "The factor leading to gut leakiness is not known, however. Our study suggests that disruption of circadian rhythms and sleep, which is part of life in industrial societies, can promote it and explain the susceptibility."
In the study, the Northwestern and Rush researchers used two independent approaches, studying both genetic and environmental animal models. The circadian rhythms of one group of mice were disrupted genetically: Each animal had a mutant CLOCK gene, which regulates circadian rhythms. The second group's circadian rhythms were disrupted environmentally: The animals' light-dark cycle was changed periodically, leading to a state similar to chronic jet lag.
Mice in both groups, prior to ingesting alcohol, showed an increase in gut leakiness.
Next, both groups of mice were fed alcohol. After only one week, animals in both groups showed a significant additional increase in gut leakiness, compared to control mice on an alcohol-free diet. At the end of the three-month study, mice in both groups were in the early stages of alcoholic liver disease.
"We have clearly shown that circadian rhythm disruption can trigger gut leakiness, which drives the more severe pathology in the liver," said Keith Summa, a co-first author of the study and an M.D./Ph.D. candidate working in Turek's lab.
"For humans, circadian rhythm disruption typically is environmental, not genetic, so individuals have some control over the behaviors that cause trouble, be it a poor sleep schedule, shift work or exposure to light at night," he said.
Sleep and circadian rhythms are an integral part of biology and should be part of the discussion between medical doctors and their patients, the researchers believe.
"We want to personalize medicine from a time perspective," Turek said. "Our bodies are organized temporally on a 24-hour basis, and this needs to be brought into the equation for understanding health and disease."
###
The paper, titled "Disruption of the Circadian Clock in Mice Increases Intestinal Permeability and Promotes Alcohol-Induced Pathology and Inflammation," is available at http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0067102.
In addition to Turek, Keshavarzian and Summa, other authors of the paper are co-first author Robin M. Voigt, Christopher B. Forsyth, Maliha Shaikh and Yueming Tang, of Rush University Medical Center; Martha Hotz Vitaterna and Kate Cavanaugh, of Northwestern; and Shiwen Song, of the American Society for Clinical Pathology.
[ | E-mail | Share ]
?
AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert! system.
![[ Back to EurekAlert! ]](http://www.eurekalert.org/images/back2e.gif){kind=small}
Public release date: 1-Jul-2013
Share ]