Hang around in the tech industry long enough and you or someone you know will be heard saying, "that's so crazy it just might work." Two years ago, if you'd told me that an open-source, P2P currency would soon be a thriving, billion-dollar market, I would've told you that you were on a lonely bus headed to CrazyTown, U.S.A. But today, Bitcoin officially became a crazy idea that's actually working. Today, all the Bitcoin in circulation -- some 10.9 million -- have collectively crossed the billion-dollar mark. As it is wont to do, the value of Bitcoin (and its exchange rate) has fluctuated wildly today. At one point, it hit a dollar value around $78, then pushed into the mid-nineties. As of this minute, it's hovering around $90.
The whole syncing thing proving too much effort for your music listening habits? Fear not -- two new streaming speakers from Sony are embracing the world of near field communication to take some of the trouble out of playback. The speakers come in two flavors -- the CMT-BT60B does Bluetooth streaming and the similarly alphanumeric CMT-BT80WB will stream via Bluetooth, WiFi or AirPlay. Both speakers feature aux inputs and USB for charging (and playback, in the case of the BT80WB). As for, you know, making sound, both feature Magnetic Fluid Speakers and S-Master amplifiers. They'll be hitting parts of Europe in May and the UK in June.
If you are one of the players in the online business industry, then you are more likely concerned with your online brand image. A good online repute is central to attracting and maintaining business customers. With the seemingly universal implementation of social media among consumers, brands can now eavesdrop on conversations on the subject of their goods and services. While it?s not feasible to control these conversations, companies can monitor and act upon them. Often, brand followers and critics are somewhat vocal in equal measure, and all those reviews and opinions are available on the internet, if you use the right social media tools for monitoring purposes.
Every good discussion begins with listening. Social media monitoring tools are available to help you take note of the discussion, engage, and become proactive. Traditionally, brands prefer to listen before responding and avoid damage control. Nonetheless, listening is far more than being reactive. Listening in on your customers is an extremely insightful experience. Here are 5 social media tools to monitor your brand in internet circles.
Google Alerts:
It is an oldie but still a valuable tool. For instance, it allows users to?create keyword searches?based on the name of their companies or business competitors. As such, users are able to receive updates through their email inboxes or via RSS feeds. When merged with iGoogle, you can set up a rather beautiful consolidated page comprising of all the latest results for the chosen keywords. In terms of social media monitoring, Google alerts is the least you should act upon; not only is it free but very easy to set up.
radian6:
It comes with a striking interaction console that allows you to listen, interact, and plan in one versatile desktop application. It is highly regarded for its ability to check the performance of all services, brands and keywords across all social network platforms all together. This is a great solution that will drive your business to uncharted waters. In terms of performance monitoring, radian6 goes beyond the major social media networks to include blogs, social forums, photographic and video websites, comments and millions of websites available online. Furthermore, this excellent social media monitoring tool?combines data from all areas across the web, filters and separates it, and mentions and chants it on behalf of users based on the different user definable and choose able metrics.
Twazzup:
This is a dashboard app that keeps an eye on Twitter. It focuses mainly on Twitter monitoring. The program will notify you whenever your keywords appear in any tweet. Additionally, it classifies your results through link popularity, tagging clouds, contributors and users. Furthermore, Twazzup is typical of unique features such as avatar mouse-overs which?give more information on the user?s appropriate tweets. These are just but a few of the many features that make Twazzup an amazingly powerful and useful social media monitoring tool.
HootSuite:
It is a well-known tool used to?run multiple accounts?across social media platforms such as Twitter, MySpace, Facebook, Word Press, LinkedIn and Foursquare. Hootsuite doubles up as an account management tool as well as a social media monitoring tool. It terms of social media monitoring, it is valuable as it has a significantly large user network and great functionality. You can post updates in more than one profile, trace click-through, set up timed updates, keep an eye on your social network happenings across several web services, and delegate tasks among group members based on responsibilities.
Scout labs:
While a number of social network monitoring tools can become complicated to make use of, Scout labs uses a plain, easy to use interface that provides powerful data to social markets that proves beneficial when tracking the brand performance. One of its special features allows users to highlight graphs to help examine trends in aggregated data. The dashboard is simple to create and comes with a composite Buzz ranking that enables you?monitor your results with a quick look. Unique categories for internet sentiment, quotes and mentions give you comprehensive knowledge of your data. It?s an excellent choice for agencies as well as freelancers as it gives customers admittance to a dashboard that has your brand logo on it.
Social media is not only an entertainment tool, but a powerful marketing tool for business. By creating your presence in social network platforms, you give your brand virtually unrestricted exposure to potential clients without facing any major cost issues. The important part is to?track your performance across the online world. The above mentioned 5 social media tools are very beneficial in terms of monitoring your brand image across different social media platforms.
Jason Smith is an online manager for?SEO company. Jason likes blogging about online strategies that are related to SEO, Content, PPC & Lead generation.
By Simon Evans MEXICO CITY, March 27 (Reuters) - United States central defenders Omar Gonzalez and Matt Besler went into Tuesday's game against Mexico at the Azteca Stadium with just two World Cup qualifying starts between them, but looked like they had been alongside each other for years in a spirited 0-0 draw. Gonzalez, making his third start in a qualifier and Besler making his first, held Mexico at bay in front of more than 95,000 fans as the U.S earned just their second point ever at the home of their arch-rivals. ...
Sunday will mark the end of the first quarter. It's been a busy three months in MMA, so it's a good time to look back at the past three months and see who rose above the rest.
Biggest upset: Did you expect to see Robbie Lawler walk away with the win over Josh Koscheck at UFC 157? What about Antonio Rogerio Nogueira beating former UFC light heavyweight champ Rashad Evans? But there's no question who scored the biggest upset of the first quarter of 2013. Antonio Silva's TKO of Alistair Overeem at UFC 156 left more than Overeem's jaw on the floor.
Best knockout: Vitor Belfort's knockout of Michael Bisping at the January UFC on FX was memorable, as was Tyron Woodley's 36-second dismantling of Jay Hieron at UFC 156. Wanderlei Silva, Robbie Lawler and a slew of Bellator fighters have posted impressive knockouts. But the one that had everyone talking was on "The Ultimate Fighter." Uriah Hall's knockout of Adam Cella* was perfectly executed, and had the rest of the TUF house worried about Hall's skills. For that, Hall wins knockout of the first quarter.
* The knockout actually occurred last year, but aired in the first quarter of 2013.
Best submission: For the best tapouts of the first three months of 2013, Bellator provided a nominee when Dave Vitkay choked out Jesse Peterson in just 18 seconds. Gabriel Gonzaga's guillotine of Ben Rothwell stands out, as is Ronda Rousey's arm bar of Liz Carmouche at UFC 157. The winner comes from the undercard of UFC 157 as Kenny Robertson managed a weird yet incredibly painful looking kneebar-esque submission of Brock Jardine. It was the kind of submission that left MMA fans wondering what had happened.
Best rising star: There were plenty of candidates for fighters who really made an impressive leap in the MMA world early in 2013. Jordan Mein's UFC debut at UFC 158 included rolling out of an arm bar with Dan Miller, and then knocking him out before the first round ended. Abel Trujillo's TKO win by knees to the body of Marcus Levesseur was pretty fantastic, too. But it's Trujillo's opponent at UFC 160, Khabib Nurmagomedov who is taking home the prize. His TKO of Thiago Tavares in Brazil showed he can fight well under any conditions.
Best fight: Johny Hendricks and Carlos Condit put on a great scrap at UFC 158. Brian Stann and Wanderlei Silva's bout was thrilling before Stann was knocked out. Demetrious Johnson and John Dodson's title fight at UFC on Fox 6 was memorable, as was Frankie Edgar and Jose Aldo's title bout at UFC 156. The one fight that stood out above the rest, though, was Dennis Bermudez and Matt Grice's fight from UFC 156. Throughout the bout, both fighters should have given up. Both fighters should have been knocked out. But neither man gave in. Bermudez won the decision, but both fighters will be remembered for this bout.
Do you agree? Speak up in the comments, on Facebook or on Twitter.
Cancer biologists find DNA-damaging toxins in common plant-based foodsPublic release date: 27-Mar-2013 [ | E-mail | Share ]
Contact: Vanessa Wasta wasta@jhmi.edu 410-614-2916 Johns Hopkins Medicine
Liquid smoke, black and green teas and coffee produced levels of cell DNA damage comparable to chemo drugs
In a laboratory study pairing food chemistry and cancer biology, scientists at the Johns Hopkins Kimmel Cancer Center tested the potentially harmful effect of foods and flavorings on the DNA of cells. They found that liquid smoke flavoring, black and green teas and coffee activated the highest levels of a well-known, cancer-linked gene called p53.
The p53 gene becomes activated when DNA is damaged. Its gene product makes repair proteins that mend DNA. The higher the level of DNA damage, the more p53 becomes activated.
"We don't know much about the foods we eat and how they affect cells in our bodies," says Scott Kern, M.D., the Kovler Professor of Oncology and Pathology at the Johns Hopkins University School of Medicine. "But it's clear that plants contain many compounds that are meant to deter humans and animals from eating them, like cellulose in stems and bitter-tasting tannins in leaves and beans we use to make teas and coffees, and their impact needs to be assessed."
Kern cautioned that his studies do not suggest people should stop using tea, coffee or flavorings, but do suggest the need for further research.
The Johns Hopkins study began a year ago when graduate student Samuel Gilbert, working in Kern's laboratory, noted that a test Kern had developed to detect p53 activity had never been used to identify DNA-damaging substances in food.
For the study, published online February 8 in Food and Chemical Toxicology, Kern and his team sought advice from scientists at the U.S. Department of Agriculture about food products and flavorings. "To do this study well, we had to think like food chemists to extract chemicals from food and dilute food products to levels that occur in a normal diet," he says.
Using Kern's test for p53 activity, which makes a fluorescent compound that "glows" when p53 is activated, the scientists mixed dilutions of the food products and flavorings with human cells and grew them in laboratory dishes for 18 hours.
Measuring and comparing p53 activity with baseline levels, the scientists found that liquid smoke flavoring, black and green teas and coffee showed up to nearly 30-fold increases in p53 activity, which was on par with their tests of p53 activity caused by a chemotherapy drug called etoposide.
Previous studies have shown that liquid smoke flavoring damages DNA in animal models, so Kern's team analyzed p53 activity triggered by the chemicals found in liquid smoke. Postdoctoral fellow Zulfiquer Hossain tracked down the chemicals responsible for the p53 activity. The strongest p53 activity was found in two chemicals: pyrogallol and gallic acid. Pyrogallol, commonly found in smoked foods, is also found in cigarette smoke, hair dye, tea, coffee, bread crust, roasted malt and cocoa powder, according to Kern. Gallic acid, a variant of pyrogallol, is found in teas and coffees.
Kern says that more studies are needed to examine the type of DNA damage caused by pyrogallol and gallic acid, but there could be ways to remove the two chemicals from foods and flavorings.
"We found that Scotch whiskey, which has a smoky flavor and could be a substitute for liquid smoke, had minimal effect on p53 activity in our tests," says Kern.
Liquid smoke, produced from the distilled condensation of natural smoke, is often used to add smoky flavor to sausages, other meats and vegan meat substitutes. It gained popularity when sausage manufacturers switched from natural casings to smoke-blocking artificial casings.
Other flavorings like fish and oyster sauces, tabasco and soy sauces, and black bean sauces showed minimal p53 effects in Kern's tests, as did soybean paste, kim chee, wasabi powder, hickory smoke powders and smoked paprika.
###
Funding for the study was provided by the National Institutes of Health's National Cancer Institute (CA62924) and the Everett and Marjorie Kovler Professorship in Pancreas Cancer Research.
In addition to Kern, Gilbert and Hossain, other scientists involved in the research include Kalpesh Patel, Soma Ghosh, and Anil Bhunia from Johns Hopkins.
On the Web:
hopkinscancer.org
Media Contacts: Vanessa Wasta, 410-614-2916
wasta@jhmi.edu
Amy Mone, 410-614-2915
amone@jhmi.edu
March 27, 2013
[ | 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.
Cancer biologists find DNA-damaging toxins in common plant-based foodsPublic release date: 27-Mar-2013 [ | E-mail | Share ]
Contact: Vanessa Wasta wasta@jhmi.edu 410-614-2916 Johns Hopkins Medicine
Liquid smoke, black and green teas and coffee produced levels of cell DNA damage comparable to chemo drugs
In a laboratory study pairing food chemistry and cancer biology, scientists at the Johns Hopkins Kimmel Cancer Center tested the potentially harmful effect of foods and flavorings on the DNA of cells. They found that liquid smoke flavoring, black and green teas and coffee activated the highest levels of a well-known, cancer-linked gene called p53.
The p53 gene becomes activated when DNA is damaged. Its gene product makes repair proteins that mend DNA. The higher the level of DNA damage, the more p53 becomes activated.
"We don't know much about the foods we eat and how they affect cells in our bodies," says Scott Kern, M.D., the Kovler Professor of Oncology and Pathology at the Johns Hopkins University School of Medicine. "But it's clear that plants contain many compounds that are meant to deter humans and animals from eating them, like cellulose in stems and bitter-tasting tannins in leaves and beans we use to make teas and coffees, and their impact needs to be assessed."
Kern cautioned that his studies do not suggest people should stop using tea, coffee or flavorings, but do suggest the need for further research.
The Johns Hopkins study began a year ago when graduate student Samuel Gilbert, working in Kern's laboratory, noted that a test Kern had developed to detect p53 activity had never been used to identify DNA-damaging substances in food.
For the study, published online February 8 in Food and Chemical Toxicology, Kern and his team sought advice from scientists at the U.S. Department of Agriculture about food products and flavorings. "To do this study well, we had to think like food chemists to extract chemicals from food and dilute food products to levels that occur in a normal diet," he says.
Using Kern's test for p53 activity, which makes a fluorescent compound that "glows" when p53 is activated, the scientists mixed dilutions of the food products and flavorings with human cells and grew them in laboratory dishes for 18 hours.
Measuring and comparing p53 activity with baseline levels, the scientists found that liquid smoke flavoring, black and green teas and coffee showed up to nearly 30-fold increases in p53 activity, which was on par with their tests of p53 activity caused by a chemotherapy drug called etoposide.
Previous studies have shown that liquid smoke flavoring damages DNA in animal models, so Kern's team analyzed p53 activity triggered by the chemicals found in liquid smoke. Postdoctoral fellow Zulfiquer Hossain tracked down the chemicals responsible for the p53 activity. The strongest p53 activity was found in two chemicals: pyrogallol and gallic acid. Pyrogallol, commonly found in smoked foods, is also found in cigarette smoke, hair dye, tea, coffee, bread crust, roasted malt and cocoa powder, according to Kern. Gallic acid, a variant of pyrogallol, is found in teas and coffees.
Kern says that more studies are needed to examine the type of DNA damage caused by pyrogallol and gallic acid, but there could be ways to remove the two chemicals from foods and flavorings.
"We found that Scotch whiskey, which has a smoky flavor and could be a substitute for liquid smoke, had minimal effect on p53 activity in our tests," says Kern.
Liquid smoke, produced from the distilled condensation of natural smoke, is often used to add smoky flavor to sausages, other meats and vegan meat substitutes. It gained popularity when sausage manufacturers switched from natural casings to smoke-blocking artificial casings.
Other flavorings like fish and oyster sauces, tabasco and soy sauces, and black bean sauces showed minimal p53 effects in Kern's tests, as did soybean paste, kim chee, wasabi powder, hickory smoke powders and smoked paprika.
###
Funding for the study was provided by the National Institutes of Health's National Cancer Institute (CA62924) and the Everett and Marjorie Kovler Professorship in Pancreas Cancer Research.
In addition to Kern, Gilbert and Hossain, other scientists involved in the research include Kalpesh Patel, Soma Ghosh, and Anil Bhunia from Johns Hopkins.
On the Web:
hopkinscancer.org
Media Contacts: Vanessa Wasta, 410-614-2916
wasta@jhmi.edu
Amy Mone, 410-614-2915
amone@jhmi.edu
March 27, 2013
[ | 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.
Months before its official release, the backlash against Google?s next gen headset Google Glass seems to be gaining momentum. Last week, an online ?Stop the Cyborgs? campaign?launched to raise concerns about the impact of the hands-free Internet devices on society and, in an even broader sense, humanity as a whole. Now, individual states are getting in on the act by considering the legality of the new hardware: West Virginia has introduced legislation that could see Glass being banned before it ever arrives in stores.
The legislation in question is an amendment to an existing law governing the use of cellphones while driving. Introduced to the West Virginia House of Delegates by Republican member Gary Howell, H.B. 3057 is described as ?a bill to amend and re-enact ?17C-14-15 of the Code of West Virginia, 1931, as amended, relating to traffic safety; specifically, establishing the offense of operating a motor vehicle using a wearable computer with a head-mounted display.?
Specifically, the law broadens the description of devices outlawed while operating a motor vehicle to include ?a cell telephone, personal digital assistant, electronic device with mobile data access, laptop computer, pager, broadband personal communication device, 2-way messaging device, electronic game or portable computing device.? The third of those, of course, would include Google Glass.
?Last [legislative session], we were working really hard on the ?no texting and driving? [aspect], saying you couldn?t use a handheld device,? Howell told Ars Technica about the change. ?I got to looking at Google Glass, and the way [our bill is] written, a headset is a hands-free device. So we?re going to have people driving down the road, texting and watching videos, not paying attention to what they?re doing.?
Howell shrugged off reports likening Glass to the visual input fighter pilots receive via their visors. ?In a jet fighter you?re displaying information that is critical to the operation of the vehicle. Also, pilots are talking about information overload, and they received $1 million in training to fly that thing.?
He went on to pursue the idea of ?critical information? being okay, whereas Glass?s access to the Internet as a whole would be overwhelming. ?It probably would work well for [single-use navigation] applications, but the problem is that that?s not all [Glass] does,? Howell said. ?If you had a dedicated GPS unit, then you?re probably OK. [With Google Glass,] you can watch videos. You can get texts from people. That creates the safety problem.?
In response to the legislation, a Google spokesperson said that the company ?believe[s] there is tremendous potential to improve safety on our roads and reduce accidents,? adding that it is ?putting a lot of thought into the design of Glass because new technologies always raise new issues.? And, it seems, new laws, as well.
Missoula family oriented, membership based, non-profit community service agency is seeking a Part-time ADAPTIVE & SPECIAL OLYMPICS COORDINATOR. QUALIFICATIONS: High School diploma or equivalent required; Bachelors degree or college classes in Therapeutic Recreation, Recreation Therapy or a related field preferred; or one to two years of related experience, or equivalent combination of education and experience. Preferred - Understanding of therapeutic recreation, adaptive sports and Special Olympics, as it relates to a community setting. Required; CPR and First Aid certification; valid driver's license & willingness to obtain CDL; Preferred - Experience working with children and adults with intellectual disabilities. DUTIES: Responsible for leading a variety of adaptive sports classes, programs and camps for the employer, in partnership with Special Olympics Montana. Serves as the point of contact for coaches, volunteers, staff and athletes; works collaboratively with students, staff, districts and outside agencies; plan and organize activities and trainings; recruit, train and organize volunteers. Must be able to thrive in an environment with the unique challenges of a non-profit community service organization. DAYS/HOURS: Part-time, generally, M-Th, 10+ hours a week, some Friday nights and weekends with potential to increase hours to 20+. WAGE: $8/hour or more DOE. //JRS
Open Date
3/25/2013
Close Date
4/19/2013
Experience
Education
Degree Required
High School Diploma
Skills
Shift
Day, Swing
Availability
Part
Days Off
Openings
1
Work Schedule
10+ hrs/wk; Potential of 20hrs/wk
Lifting Capacity
Driver License
Standard
Endorsements
Job Benefits
Commission
No
By selecting "How to Apply" your name couldbe shared with this employer
Back in February, "Warm Bodies," the one-of-a-kind zombie rom-com, brought life to our cold, dead hearts, so now we're happy to exclusively announce that you'll be able to bring home the story of R when the movie hits Blu-ray and DVD on June 4. To celebrate the announce, we've been given a special sneak peek [...]
NEW YORK (AP) ? T-Mobile USA on Tuesday said it will start offering the iPhone 5 on April 12, filling what its CEO said was "a huge void" in its phone lineup.
T-Mobile, the fourth-largest of the national U.S. phone companies, has been losing customers to the bigger companies, which all sell the iPhone.
"This is a big deal for us," T-Mobile CEO John Legere said at an event in New York.
The company is charging $100 up front for the iPhone 5, then another $20 per month for two years. That's on top of service fees for voice, text and data that start at $50 per month. The total monthly cost starts at $70 per month, a substantial discount to prices offered by bigger companies.
T-Mobile's network has, until recently, not been able to offer high-speed data service to iPhones. It's now able to deliver high-speed data to iPhones in some cities, and it has lured over 2.1 million off-contract AT&T iPhones, executives said Tuesday.
The company also announced that it is firing up an even faster data network, based on so-called "LTE" technology, in Baltimore, Houston, Kansas City, Las Vegas, Phoenix, San Jose, Calif., and Washington. Unofficially, the network is also active here and there in New York, as demonstrated at the event. By the end of the year, T-Mobile says it will be available where two-thirds of the nation's population lives. The iPhone 5 can access the LTE network for faster data downloads.
T-Mobile is the last of the four major carriers to launch an LTE network, but already has a relatively fast "4G" network. It's been hamstrung by a lack of space on the airwaves, but gained some room last year from AT&T as part the compensation for a failed buyout attempt.
T-Mobile also said it will start selling the Samsung Galaxy S 4 on or around May 1. That's the successor to the Galaxy S III, which has been the chief competitor to the iPhone.
The announcement comes just days after T-Mobile ditched its conventional contract-based plans in favor of selling phones on an installment basis. It's separating the cost of the phone from the service, and when a phone is paid off, usually after two years, the monthly fee for the phone disappears from the billing statement.
On traditional contract-based plans still used by the other carriers, the buyer is deemed to have "paid off" the phone after a certain period, at which point the customer becomes eligible for a new, subsidized phone. The monthly payments, however, don't decline if the customer keeps the old phone. There's no service contract, so customers are free to jump from T-Mobile to another carrier at any point, but they'll still be paying off their T-Mobile phone in monthly installments.
T-Mobile is positioning the change as a radical departure from industry practices, and is basing a new advertising campaign on being the "Uncarrier."
"We're cancelling our membership in the carrier club," Legere said.
As before, T-Mobile's prices generally undercut those of the bigger phone companies. The chief weakness is that its data network coverage is poorer in rural areas.
"T-Mobile realizes that they have to change the rules of the game, because under the current rules, they're losing, and they're going to continue to lose," said telecommunications analyst Roger Entner at Recon Analytics. He's skeptical that the plans, alone, can change its fortunes.
"Even if they're $5 cheaper, will that be enough? They're already charging a significant discount to Verizon and AT&T, and they're losing customers," Entner said.
T-Mobile is a unit of Germany's Deutsche Telekom AG, which has agreed to merge it with No. 5 carrier MetroPCS Communications Inc. That deal faces opposition from shareholders of MetroPCS, which provides only prepaid service. By coincidence, the shareholders are voting on the merger on April 12, the same day T-Mobile starts selling the iPhone.
JOHANNESBURG (AP) ? Human rights activists from Brazil, Russia, India, China and South Africa are appealing to their leaders to use their influence to press Syria to allow unimpeded humanitarian access to U.N. agencies.
Camila Asano of Brazil's Conectas says it is "a responsibility" for leaders of a BRICS summit starting Tuesday in South Africa to act to protect Syrian civilians.
Human Rights Watch director Jan Egeland wrote separately that it is "time for BRICS to stop sitting on the fence over Syria's atrocities."
BRICS countries oppose foreign intervention in Syria and accuse the West of forcing regime change. Russia, China and South Africa have vetoed U.N. Security Council resolutions on Syria.
The U.N. estimates some 70,000 people have been killed since Syria's civil war began with peaceful protests two years ago.
'Have No Regrets' --Richard Branson, Founder of Virgin Group
"The best advice I ever received? Simple: Have no regrets. Who gave me the advice? Mum?s the word. "If you asked every person in the world who gave them their best advice, it is a safe bet that most would say it was their mother. I am no exception. My mother has taught me many valuable lessons that have helped shape my life. But having no regrets stands out above all others, because it has informed every aspect of my life and every business decision we have ever made." Source: <a href="http://www.linkedin.com/today/se/bestadvice">LinkedIn</a>
'Keep Listening' --Pete Cashmore, CEO of Mashable
"... I had access to the best guidance available: We all do. In the era of blogging, many of the leading thinkers in the web industry were publishing their thoughts online for free. I learned about venture capital thanks to the insights of Fred Wilson, and got my first look at the world of digital marketing thanks to Edelman?s Steve Rubel. Charlene Li of Forrester Research was unknowingly my mentor in the realm of web trends. Now many of these industry experts have moved to newer platforms like Twitter and Facebook, where they continue to distill their invaluable advice and insights to the world. And everyday (sic), without knowing it, they are actually giving me the best advice: Keep listening." Source: <a href="http://www.linkedin.com/today/se/bestadvice">LinkedIn</a>
'Take Time To Get To Know People' --Beth Comstock, Chief Marketing Officer, GE
"Moving fast and being organized were my strong suits. The more there was to do, the more I felt alive." Who better than me, then, to land a plum assignment working for Jack Welch, Mr. Speed and Simplicity. Imagine my surprise when he called me into his office that day and admonished me for being too efficient. My zeal to do everything on my to-do list ? along with my reserved, even shy nature ? made me come across as abrupt and cold. I started every meeting by jumping right in and left with every action under control. 'You have to wallow in it,' he said. 'Take time to get to know people. Understand where they are coming from, what is important to them. Make sure they are with you.' I heard Jack loud and clear. But honestly, it took a long time for the impact of his words to sink in, and even longer to change my behavior. After all, those same attributes had led to my being in the role in the first place." Source: <a href="http://www.linkedin.com/today/se/bestadvice">LinkedIn</a>
'You Can Do Anything You Choose' --Martha Stewart, Founder of Martha Stewart Living Omnimeda
"The best advice I?ve ever received was from my father when I was 12 years old and willing to listen. He told me that with my personal characteristics, I could, if I set my mind to it, do anything I chose. This advice instilled in me a great sense of confidence, and despite the fact that sometimes I was a little nervous, I stepped out and did what I wanted to do when I wanted to do it. I think it really often is up to the parents to help build confidence in their children. It is a very necessary part of growing up." Source: <a href="http://www.linkedin.com/today/se/bestadvice">LinkedIn</a>
'Sit On Your Own Bottom' --T. Boone Pickens, Chairman of BP Capital Management
"If I had to single out one piece of advice that?s guided me through life, most likely it would be from my grandmother, Nellie Molonson. She always made a point of making sure I understood that on the road to success, there?s no point in blaming others when you fail. Here?s how she put it: 'Sonny, I don?t care who you are. Some day you?re going to have to sit on your own bottom.' After more than half a century in the energy business, her advice has proven itself to be spot-on time and time again. My failures? I never have any doubt whom they can be traced back to. My successes? Most likely the same guy." Source: <a href="http://www.linkedin.com/today/se/bestadvice">LinkedIn</a>
'You Can Do Anything You Set Your Mind To' --Jeff Weiner, CEO of LinkedIn
"As a child, I can't recall a day that went by without my dad telling me I could do anything I set my mind to. He said it so often, I stopped hearing it ... It wasn't until decades later that I fully appreciated the importance of those words and the impact they had on me." Source: <a href="http://www.linkedin.com/today/se/bestadvice">LinkedIn</a>
'Plan Your Pricing From The Target Customer's Perspective' --Shai Agassi, Founder of Better Place
At a conference in 2006, President Clinton gave Agassi some advice on pricing for market disruption: "'By the time you will convince the rich folks in Israel to try it, then get the average folks in Israel to try it, then bring it to the U.S. for our rich folks ... the world will run out of time. You need to price your car so that an average Joe would prefer it over the kind of cars they buy today ? an 8-year-old used gasoline car, selling for less than $3,000. As a matter of fact, if you can give away your car for free, that's a sure way to succeed.' Pricing for market disruption is very different than pricing for a few early adopters. You have to plan your pricing from the target customer's perspective, within the boundaries of your costs." Source: <a href="http://www.linkedin.com/today/se/bestadvice">LinkedIn</a>
'Don't Correct People When It Matters Little' --Craig Newmark, Founder of Craigslist
"I'm a nerd, seriously hard-core, and sometimes that translates into being a know-it-all. People got tired of that while I worked at an IBM branch office in Detroit in the eighties. My boss told that that it had become a real problem with about half my co-workers. However, he said that my saving grace was my sense of humor. When trying to be funny, well, didn't matter if I was funny or not, at least I wasn't being an a**hole. The advice was to focus on my sense of humor and worry less about being exactly right. For sure, don't correct people when it matters little." It took a while to get noticed, but it did get noticed, and some tension got less tense. That felt pretty good. Source: <a href="http://www.linkedin.com/today/se/bestadvice">LinkedIn</a>
'Feed The Eagles And Starve the Turkeys' --Nilofer Merchant, Founder of Rubicon Consulting
"When I was 20-something ... I walked into my boss?s office, the division leader ... I told him that I felt like on any given day I was facing a tsunami of things I could pay attention to, and there was no way I could work any harder to make stuff happen. I was asking for more resources, as the answer. And he sat me down as he might one of his many kids and gave me this advice: Feed the Eagles and Starve the Turkeys. Feed the Eagles. There are only a few things that matter. Know what they are. And place your energy into them. They aren?t always right in front of you so you need to look up and out more. Starve the Turkeys ? lots of things are right in front of you ? pecking around, making noise, and demanding attention. Because they are right in front of you, it?s easy to pay attention to them most and first. Ignore them. They will actually do fine without you." Source: <a href="http://www.linkedin.com/today/se/bestadvice">LinkedIn</a>
'You Are Not Required To Finish Your Work, Yet Neither Are You Permitted To Desist From It' --Michael Fertik, CEO at Reputation.com
"'You are not required to finish your work, yet neither are you permitted to desist from it.' This is from Pirke Aboth, or ?The Ethics of the Fathers? ... a collection of wisdom from the Jewish Talmudic sages, in this case, Rabbi Tarfon. This particular instruction has resonated with me for years. It?s something I think about nearly each day, and I find myself applying it to everything: My day job, my family life, my long-term hopes, even my sense of responsibility as a citizen. It?s a beautiful concept. It says you have an obligation to labor, to continue trying and making your way through the world, in essence, making a difference. At the same time, the instruction also focuses you on the effort, not the outcome. The main idea is the project, not the success." Source: <a href="http://www.linkedin.com/today/se/bestadvice">LinkedIn</a>
'Never Travel Away From Your Wife For More Than 10 Days At A Time' --Tim Brown, CEO of Ideo
"I received one of my most valuable and sustaining pieces of advice from my mentor Bill Moggridge soon after I started working with him in the late 1980's. He had something called the '10 day rule' that he applied religiously to his own life and suggested strongly that I did the same to mine. The 10 day rule dictated that he was never allowed to travel away from his wife, Karin, for more than 10 days at a time. He would go to whatever lengths necessary to make it back home within the 10 days even if it meant flying the next day to another client meeting. His view was that this design constraint made him more efficient with travel and also reminded him to keep a balance between home and work life. I have found both of these to be true and have applied the 10 day rule throughout my career. I am convinced it has helped me maintain a great relationship with my own wife, Gaynor, for the last 27 years." Source: <a href="http://www.linkedin.com/today/se/bestadvice">LinkedIn</a>
'When You Want Something From Someone, Give Them Something Instead' --Dave Kerpen, CEO of Likeable Local
"My father-in-law, the Honorable Steven W. Fisher ... taught me this essential business paradox: when you want something from someone, give them something instead, with no strings attached or expectations. Ask how you can be of service. Act like a true friend, even before you?ve established a friendship. Are you guaranteed to be able to leverage this later? Absolutely not. But that?s not the point ? the point is that when you act unselfishly ? when you behave as you would to a great friend ? trustworthy and trusting, respectful and kind ? then more often than not, good things will come in the relationship." Source: <a href="http://www.linkedin.com/today/se/bestadvice">LinkedIn</a>
'Follow Your Instincts' --Michael Moritz, Chairman of Sequoia Capital
"'Follow your instincts' was the terse, three-word suggestion I received 25 years ago from Don Valentine, founder of Sequoia Capital. 'Follow your instincts' shouldn?t be confused with 'trust your gut,' 'ignore reality,' 'rely on your sniffer' or 'go for glory.' The rough translation is 'do your homework well, analyze things carefully, assess the options but eventually trust your judgment and have the courage of your convictions ? even if they are unpopular." Source: <a href="http://www.linkedin.com/today/se/bestadvice">LinkedIn</a>
'Don?t Be A Perfectionist' --Ilya Pozin, Founder of Ciplex
"Most of us are trained to believe that practice makes perfect; but the best advice I've ever received preaches the exact opposite: Don?t be a perfectionist. Today I embrace this, but when I first heard this 7 years ago, I refused to accept it." Source: <a href="http://www.linkedin.com/today/se/bestadvice">LinkedIn</a>
'Pack Half As Much Stuff As You Think You'll Need, And Twice As Much Money' --Hilary Mason, Chief Scientist at Bitly
"I've heard and read quite a lot of good advice, most of which I've probably ignored, but one thing that I did internalize was a bit of advice about, oddly enough, travel: pack half as much stuff as you think you'll need, and twice as much money. The more I travel this way the more I bring the same attitude to every new project. You can't know what's going to happen, so don't worry ? just take what you need, and jump in." Source: <a href="http://www.linkedin.com/today/se/bestadvice">LinkedIn</a>
'Take The Blame When You Deserve It' --Gretchen Rubin, Author and Blogger
"My father: 'If you?re willing to take the blame when you deserve it, people will give you the responsibility.' This was perhaps the best advice for the workplace I ever got." Source: <a href="http://www.linkedin.com/today/se/bestadvice">LinkedIn</a>
'Losing Doesn't Matter' --Nicholas Thompson, Senior Editor at The New Yorker Magazine
Thompson's former soccer coach, Bruce Cochrane, told him that losing doesn't matter: "It sounds like a trite lesson now: another version of 'it's not whether you win or lose, it's how you play the game.' But it was much more powerful. He was explaining that there was a certain artistry to what we were trying to do, and a certain dignity that we had upheld even in defeat." Source: <a href="http://www.linkedin.com/today/se/bestadvice">LinkedIn</a>
'Are You Happy?' --Jeffrey Selingo, Columnist and Author
"The advice came from Clint Williams, an editor at the paper. Near the end of the summer, many of the fellows were figuring out where to focus our job search or weighing job offers. Many of us didn?t know what to do next. What would make us happy? Clint had a rule of thirds for happiness in life. He told me to ask three questions: Are you happy with your job? Are you happy where you live? Are you happy who you?re with (depending on your circumstances that could mean friends, spouse, partner, etc). If you answer Yes to at least two out of three, you found your spot for the moment. If not, you need to make a change to one of them." Source: <a href="http://www.linkedin.com/today/se/bestadvice">LinkedIn</a>
Evaluate Your Career Every 18 Months --Charlene Li, Founder Partner at Altimeter Group
"In my second year at Harvard Business School, I took a career management course because I had no idea what I was going to do upon graduation. At the start of the course, the professor gave me the best advice: That the most important asset I would ever manage would be my career and because of that, I should give it the proper time, attention and investment that it deserved. No other asset I would ever manage would ever come close to the net present value of my career." His specific advice was to evaluate my career status about every 18 months. It's 18 months because that's about how long it takes for a person to master a job ? and begin to look for new challenges. Either you find those challenges in the existing job or you have to and find new opportunities. Regardless, that regular evaluation keeps you honest about managing your career, rather than passively going along with the situation that you are currently in." Source: <a href="http://www.linkedin.com/today/se/bestadvice">LinkedIn</a>
Listen To Feedback From Your Team --Jim Kim, President at The World Bank
"... I received some great advice from Marshall Goldsmith, one of the preeminent authorities in the field of leadership. He told me this: 'If you want to be an effective leader, listen to and accept with humility the feedback that comes from your team.' The most fundamental commitment you have to make as a leader is to humbly listen to the input of others, take it seriously, and work to improve. Again, it sounds simple, but it?s not easy. Leadership, as Marshall always says, is a contact sport, and one has to constantly ask for and respond to advice from colleagues so you can improve." Source: <a href="http://www.linkedin.com/today/se/bestadvice">LinkedIn</a>
Ignore The Chattering Crowds And Set Your Own Course --Sallie Krawcheck, Former President of Merrill Lynch
"One day, after some petty humiliation, I came home in tears. My mother sat me down and told me, in a voice that I thought of as her 'telephone voice' (meaning, reserved for grown-ups), that I should ignore the girls [from school]; the only reason they were treating me poorly was because they were jealous of me. Therefore I should ignore the chattering crowds and set my own course." Source: <a href="http://www.linkedin.com/today/se/bestadvice">LinkedIn</a>
Never Show How Upset You Are --Peter Guber, CEO of Mandalay Entertainment
Pat Riley, President of the Miami Heat, told Guber to never visibly show how upset you are: "You are going to lose a lot! A lot! Get used to it! It?s a crucial part of the process! That behavior doesn?t help you or your team. You?ve got to always remain visibly positive! Managing losses is a challenge you must be up to! You can never give in to it!" Source: <a href="http://www.linkedin.com/today/se/bestadvice">LinkedIn</a>
'You're Never As Good As Your Best Review, And Never As Bad As Your Worst' --Vivian Schiller, Chief Digital Officer at NBC News
"You're never as good as your best review, and never as bad as your worst.' I was given this advice by a former boss, and it has since stuck with me as a guide for getting through the best of times and the worst of times. Looking back on my career and all of the places I?ve been, there have been incredible highs and lows at each point along the way. What I?ve come to learn is that life is cyclical and the best way to stay focused is to ignore the swings and instead focus on the long run." Source: <a href="http://www.linkedin.com/today/se/bestadvice">LinkedIn</a>
British police officers cordon off a road near a residence in Ascot, a town 40 kilometers (25 miles) west of London, Saturday, March 23, 2013. Boris Berezovsky, 67, a self-exiled and outspoken former Russian oligarch who had a bitter falling out with Russian President Vladimir Putin, was found dead Saturday in southeast England. Thames Valley police said his death was being treated as unexplained. They would not directly identify him, but when asked about him by name they read a statement saying they were investigating the death of a 67-year-old man at a property in Ascot. A mathematician turned Mercedes dealer, Berezovsky amassed his wealth during Russia's chaotic privatization of state assets in the early 1990's. The one-time Kremlin powerbroker fell out with Putin and sought political asylum in Britain in the early 2000's. He has lived in the U.K. ever since. (AP Photo/Lefteris Pitarakis)
British police officers cordon off a road near a residence in Ascot, a town 40 kilometers (25 miles) west of London, Saturday, March 23, 2013. Boris Berezovsky, 67, a self-exiled and outspoken former Russian oligarch who had a bitter falling out with Russian President Vladimir Putin, was found dead Saturday in southeast England. Thames Valley police said his death was being treated as unexplained. They would not directly identify him, but when asked about him by name they read a statement saying they were investigating the death of a 67-year-old man at a property in Ascot. A mathematician turned Mercedes dealer, Berezovsky amassed his wealth during Russia's chaotic privatization of state assets in the early 1990's. The one-time Kremlin powerbroker fell out with Putin and sought political asylum in Britain in the early 2000's. He has lived in the U.K. ever since. (AP Photo/Lefteris Pitarakis)
FILE - In this Jan. 26, 2000 file photo Russian tycoons Boris Berezovsky, left, and Roman Abramovich, then both lawmakers, walk after the session of the State Duma, parliament's lower house, in Moscow, Russia. United Kingdom police have said that Berezovsky has been found dead Saturday March 23, 2013. (AP Photo/Ivan Sekretarev, File)
British police officers cordon off a road near a residence in Ascot, a town 40 kilometers (25 miles) west of London, Saturday, March 23, 2013. Boris Berezovsky, 67, a self-exiled and outspoken former Russian oligarch who had a bitter falling out with Russian President Vladimir Putin, was found dead Saturday in southeast England. Thames Valley police said his death was being treated as unexplained. They would not directly identify him, but when asked about him by name they read a statement saying they were investigating the death of a 67-year-old man at a property in Ascot. A mathematician turned Mercedes dealer, Berezovsky amassed his wealth during Russia's chaotic privatization of state assets in the early 1990's. The one-time Kremlin powerbroker fell out with Putin and sought political asylum in Britain in the early 2000's. He has lived in the U.K. ever since. (AP Photo/Lefteris Pitarakis)
FILE - A Wednesday, July 18, 2007 photo from files showing Russian exile Boris Berezovsky, a close friend of former Russian agent Alexander Litvinenko who was poisoned by Polonium 2-10, speaking to the media in a news conference in London. United Kingdom police have said that Berezovsky has been found dead Saturday March 23, 2013. (AP Photo/Sang Tan, File)
FILE - A Friday, Aug. 31, 2012 photo from files showing Russian tycoon Boris Berezovsky talking to the media after losing his case against Russian oligarch Roman Abramovich as he leaves the High Court in London. United Kingdom police have said that Berezovsky has been found dead Saturday March 23, 2013.(AP Photo/Sang Tan, File)
LONDON (AP) ? Chemical and radiation experts found no hazardous materials in their search of the property where Boris Berezovsky's body was found, as British police on Sunday investigated the unexplained death of the self-exiled Russian tycoon who went from Kremlin kingmaker to fiery critic.
Berezovsky, who fled to Britain in the early 2000s after a bitter falling out with Russian President Vladimir Putin, was found dead Saturday at the property in Ascot, a town 40 kilometers (25 miles) west of London. He was 67, and Thames Valley police say his death is being treated as "unexplained."
Police said Sunday that officers specially trained in chemical, biological, radiological and nuclear materials have given the scene the "all clear."
"Officers found nothing of concern in the property and we are now progressing the investigation as normal," a statement from police said, adding that the majority of the cordon put in place around the property has now been lifted.
Berezovsky ? who had survived a number of assassination attempts ? amassed a fortune through oil and automobiles during Russia's chaotic privatization of state assets following the collapse of the Soviet Union in the early 1990s.
Once a member of Russian President Boris Yeltsin's inner circle, Berezovsky fell out with Yeltsin's successor, Putin, and fled Britain in the early 2000s to escape fraud charges that he said were politically motivated.
He became a strident and frequent critic of Putin, accusing the leader of ushering in a dictatorship, and accused the security services of organizing the 1999 apartment house bombings in Moscow and two other Russian cities that became a pretext for Russian troops to sweep into Chechnya for the second war there in half a decade.
Putin's spokesman acknowledged Sunday that the Russian president considered Berezovsky an enemy with clearly stated intentions to fight.
"We know for certain that he spared no expense in support of processes, within Russia and beyond, that could be said to have been directed against Russia and Putin," spokesman Dmitry Peskov said on the independent cable television channel Rain. "He definitely was Putin's opponent, and unfortunately not only his political opponent, but most likely in other dimensions as well."
In recent years, Berezovsky fended off legal attacks that often bore political undertones ? and others that bit into his fortune.
Russia repeatedly sought to extradite on Berezovksy on a wide variety of criminal charges, and the tycoon vehemently rejected allegations over the years that he was linked to several deaths, including that of slain journalist Anna Politkovskaya and ex-KGB agent Alexander Litvinenko.
Berezovsky won a libel case in 2010 against a Kremlin-owned broadcaster that aired a show in which it was suggested he was behind the poisoning of Litvinenko, who had fled Russia with Berezovsky's help after accusing officials there of plotting to assassinate political opponents.
He took a hit with his divorce from Galina Besharova in 2010, paying what was at the time Britain's largest divorce settlement. The figure beat a previous record of 48 million pounds ($73.1 million) and was estimated as high as 100 million pounds, though the exact figure was never confirmed.
Last year, Berezovsky lost a multibillion-pound High Court case against fellow Russian Roman Abramovich and was ordered to pay 35 million pounds ($53.3 million) in legal costs.
Berezovsky had claimed that Abramovich, the billionaire owner of Chelsea Football Club, cheated him out of his stakes in the oil group Sibneft, arguing that he blackmailed him into selling the stakes vastly beneath their true worth after he lost Putin's good graces.
But a judge threw out the case in August, ruling that Berezovsky was a dishonest and unreliable witness, and rejected Berezovsky's claims that he was threatened by Putin and Alexander Voloshin, a Putin ally, to coerce him to sell his Sibneft stake.
It also recently emerged that Berezovsky ran up legal bills totaling more than 250,000 pounds in just two months of a case against his former partner, Elena Gorbunova, with whom he had two children and who claimed the businessman owed her millions.
Earlier this week, The Times of London newspaper reported that Berezovsky was selling property ? including an Andy Warhol portrait of the former Soviet Union leader Vladimir Lenin ? to settle his debts and pay expenses owed to lawyers.
News of Berezovsky's death has prompted conspiracy theories along with speculation as to his state of mind, given his recent financial setbacks.
Ilya Zhegulev, a journalist with the Russian edition of Forbes magazine, said he spoke with Berezovsky the day before he died and discussed the tycoon's decision to flee Russia in 2000.
The journalist quoted Berezovsky as saying that during his years in London he had lost the meaning of life.
"I no longer want to be involved in politics," Zhegulev quoted Berezovsky as saying in a story published Saturday on the Forbes.ru website.
He said Berezovsky told him that he wanted nothing more than to return to Russia. The former oligarch said he had changed his views on Russia, saying he now understood that it should not look to Europe as a model.
"I had absolutely, idealistically imagined that it was possible to build a democratic Russia. And idealistically imagined what democracy was in the center of Europe. I underestimated the inertia of Russia and greatly overestimated the West. This took place gradually. I changed my understanding of Russia's path," he quoted Berezovsky as having said.
___
AP writer Lynn Berry in Moscow contributed to this report. Cassandra Vinograd can be reached at http://twitter.com/CassVinograd
T-cell therapy eradicates an aggressive leukemia in 2 childrenPublic release date: 25-Mar-2013 [ | E-mail | Share ]
Contact: Holly Auer holly.auer@uphs.upenn.edu 215-200-2313 University of Pennsylvania School of Medicine
CHOP/PennMedicine Oncology team reports complete remission in pediatric ALL patients
Philadelphia, March 25, 2013 - Two children with an aggressive form of childhood leukemia had a complete remission of their disease-showing no evidence of cancer cells in their bodies-after treatment with a novel cell therapy that reprogrammed their immune cells to rapidly multiply and destroy leukemia cells. A research team from The Children's Hospital of Philadelphia and the University of Pennsylvania published the case report of two pediatric patients Online First today in The New England Journal of Medicine. It will appear in the April 18 print issue.
One of the patients, 7-year-old Emily Whitehead, was featured in news stories in December 2012 after the experimental therapy led to her dramatic recovery after she relapsed following conventional treatment. Emily remains healthy and cancer-free, 11 months after receiving bioengineered T cells that zeroed in on a target found in this type of leukemia, called acute lymphoblastic leukemia (ALL).
The other patient, a 10-year-old girl, who also had a complete response to the same treatment, suffered a relapse two months later when other leukemia cells appeared that did not harbor the specific cell receptor targeted by the therapy.
"This study describes how these cells have a potent anticancer effect in children," said co-first author Stephan A. Grupp, M.D., Ph.D., of The Children's Hospital of Philadelphia, where both patients were treated in this clinical trial. "However, we also learned that in some patients with ALL, we will need to further modify the treatment to target other molecules on the surface of leukemia cells."
Grupp is the director of Translational Research for the Center for Childhood Cancer Research at The Children's Hospital of Philadelphia, and a professor of Pediatrics at the Perelman School of Medicine at the University of Pennsylvania. Michael Kalos, Ph.D., an adjunct associate professor in the department of Pathology and Laboratory Medicine in the Perelman School of Medicine at Penn, is co-first author on the study.
The current study builds on Grupp's ongoing collaboration with Penn Medicine scientists who originally developed the modified T cells as a treatment for B-cell leukemias. The Penn team reported on early successful results of a trial using this cell therapy in three adult chronic lymphocytic leukemia (CLL) patients in August of 2011. Two of those patients remain in remission more than 2 years following their treatment, and as the Penn researchers reported in December 2012 at the annual meeting of the American Society of Hematology, seven out of ten adult patients treated at that point responded to the therapy. The team is led by the current study's senior author, Carl H. June, M.D., the Richard W. Vague Professor in Immunotherapy in the department of Pathology and Laboratory Medicine and the Perelman School of Medicine at the University of Pennsylvania and director of Translational Research in Penn's Abramson Cancer Center.
"We're hopeful that our efforts to treat patients with these personalized cellular therapies will reduce or even replace the need for bone marrow transplants, which carry a high mortality risk and require long hospitalizations," June said. "In the long run, if the treatment is effective in these late-stage patients, we would like to explore using it up front, and perhaps arrive at a point where leukemia can be treated without chemotherapy."
The research team colleagues adapted the original CLL treatment to combat another B-cell leukemia: ALL, which is the most common childhood cancer. After decades of research, oncologists can currently cure 85 percent of children with ALL. Both children in the current study had a high-risk type of ALL that stubbornly resists conventional treatments.
The new study used a relatively new approach in cancer treatment: immunotherapy, which manipulates the immune system to increase its cancer-fighting capabilities. Here the researchers engineered T cells to selectively kill another type of immune cell called B cells, which had become cancerous.
T cells are the workhorses of the immune system, recognizing and attacking invading disease cells. However, cancer cells fly under the radar of immune surveillance, evading detection by T cells. The new approach custom-designs T cells to "see" and attack the cancer cells.
The researchers removed some of each patient's own T cells and modified them in the laboratory to create a type of CAR (chimeric antigen receptor) cell called a CTL019 cell. These cells are designed to attack a protein called CD19 that occurs only on the surface of certain B cells.
By creating an antibody that recognizes CD19 and then connecting that antibody to T cells, the researchers created in CTL019 cells a sort of guided missile that locks in on and kills B cells, thereby attacking B-cell leukemia. After being returned to the patient's body, the CTL019 cells multiply a thousand times over and circulate throughout the body. Importantly, they persist for months afterward, guarding against a recurrence of this specific type of leukemia.
While the CTL019 cells eliminate leukemia, they also can generate an overactive immune response, called a cytokine release syndrome, involving dangerously high fever, low blood pressure, and other side effects. This complication was especially severe in Emily, and her hospital team needed to provide her with treatments that rapidly relieved the treatment-related symptoms by blunting the immune overresponse, while still preserving the modified T cells' anti-leukemia activity.
"The comprehensive testing plan that we have put in place to study patients' blood and bone marrow while they're undergoing this therapy is allowing us to be able to follow how the T cells are behaving in patients in real time, and guides us to be able to design more detailed and specific experiments to answer critical questions that come up from our studies," Kalos said.
The CTL019 therapy eliminates all B cells that carry the CD19 cell receptor: healthy cells as well as those with leukemia. Patients can live without B cells, although they require regular replacement infusions of immunoglobulin, which can be given at home, to perform the immune function normally provided by B cells.
The research team continues to refine their approach using this new technology and explore reasons why some patients may not respond to the therapy or may experience a recurrence of their disease. Grupp said the appearance of the CD19-negative leukemia cells in the second child may have resulted from her prior treatments. Unlike Emily, the second patient had received an umbilical cord cell transplant from a matched donor, so her engineered T cells were derived from her donor (transplanted) cells, with no additional side effects. Oncologists had previously treated her with blinatumomab, a monoclonal antibody, in hopes of fighting the cancer. The prior treatments may have selectively favored a population of CD19-negative T cells.
"The emergence of tumor cells that no longer contain the target protein suggests that in particular patients with high-risk ALL, we may need to broaden the treatment to include additional T cells that may go after additional targets," added Grupp. "However, the initial results with this immune-based approach are encouraging, and may later even be developed into treatments for other types of cancer."
###
Funding from the National Institutes of Health (grants 1RO1 CA165206, R01 CA102646 and R01 CA116660), the Leukemia and Lymphoma Society, and the Alliance for Cancer Gene Therapy supported this study.
In August 2012, the University of Pennsylvania and Novartis announced an exclusive global research and licensing agreement to further study and commercialize these novel cellular immunotherapies using chimeric antigen receptor (CAR) technologies. As part of the transaction, Novartis acquired exclusive rights from Penn to CART-19, the therapy that was the subject of this clinical trial and which is now known as CTL019.
"Chimeric Antigen Receptor-Modified T Cells for Acute Lymphoid Leukemia," New England Journal of Medicine, Online First, March 25, 2013. To appear in print April 18, 2013.
About The Children's Hospital of Philadelphia:
The Children's Hospital of Philadelphia was founded in 1855 as the nation's first pediatric hospital. Through its long-standing commitment to providing exceptional patient care, training new generations of pediatric healthcare professionals and pioneering major research initiatives, Children's Hospital has fostered many discoveries that have benefited children worldwide. Its pediatric research program is among the largest in the country, ranking third in National Institutes of Health funding. In addition, its unique family-centered care and public service programs have brought the 516-bed hospital recognition as a leading advocate for children and adolescents. For more information, visit http://www.chop.edu.
About Penn Medicine:
Penn Medicine is one of the world's leading academic medical centers, dedicated to the related missions of medical education, biomedical research, and excellence in patient care. Penn Medicine consists of the Raymond and Ruth Perelman School of Medicine at the University of Pennsylvania (founded in 1765 as the nation's first medical school) and the University of Pennsylvania Health System, which together form a $4.3 billion enterprise.
The Perelman School of Medicine has been ranked among the top five medical schools in the United States for the past 16 years, according to U.S. News & World Report's survey of research-oriented medical schools. The School is consistently among the nation's top recipients of funding from the National Institutes of Health, with $398 million awarded in the 2012 fiscal year.
The University of Pennsylvania Health System's patient care facilities include:
The Hospital of the University of Pennsylvania -- recognized as one of the nation's top "Honor Roll" hospitals by U.S. News & World Report; Penn Presbyterian Medical Center; and Pennsylvania Hospital -- the nation's first hospital, founded in 1751. Penn Medicine also includes additional patient care facilities and services throughout the Philadelphia region.
Penn Medicine is committed to improving lives and health through a variety of community-based programs and activities. In fiscal year 2012, Penn Medicine provided $827 million to benefit our community.
A Joint Press Release from The Children's Hospital of Philadelphia and the Perelman School of Medicine at the University of Pennsylvania
Contacts:
Rachel Salis-Silverman
The Children's Hospital of Philadelphia
Phone: 267-426-6063 Salis@email.chop.edu
Holly Auer
Perelman School of Medicine, University of Pennsylvania
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T-cell therapy eradicates an aggressive leukemia in 2 childrenPublic release date: 25-Mar-2013 [ | E-mail | Share ]
Contact: Holly Auer holly.auer@uphs.upenn.edu 215-200-2313 University of Pennsylvania School of Medicine
CHOP/PennMedicine Oncology team reports complete remission in pediatric ALL patients
Philadelphia, March 25, 2013 - Two children with an aggressive form of childhood leukemia had a complete remission of their disease-showing no evidence of cancer cells in their bodies-after treatment with a novel cell therapy that reprogrammed their immune cells to rapidly multiply and destroy leukemia cells. A research team from The Children's Hospital of Philadelphia and the University of Pennsylvania published the case report of two pediatric patients Online First today in The New England Journal of Medicine. It will appear in the April 18 print issue.
One of the patients, 7-year-old Emily Whitehead, was featured in news stories in December 2012 after the experimental therapy led to her dramatic recovery after she relapsed following conventional treatment. Emily remains healthy and cancer-free, 11 months after receiving bioengineered T cells that zeroed in on a target found in this type of leukemia, called acute lymphoblastic leukemia (ALL).
The other patient, a 10-year-old girl, who also had a complete response to the same treatment, suffered a relapse two months later when other leukemia cells appeared that did not harbor the specific cell receptor targeted by the therapy.
"This study describes how these cells have a potent anticancer effect in children," said co-first author Stephan A. Grupp, M.D., Ph.D., of The Children's Hospital of Philadelphia, where both patients were treated in this clinical trial. "However, we also learned that in some patients with ALL, we will need to further modify the treatment to target other molecules on the surface of leukemia cells."
Grupp is the director of Translational Research for the Center for Childhood Cancer Research at The Children's Hospital of Philadelphia, and a professor of Pediatrics at the Perelman School of Medicine at the University of Pennsylvania. Michael Kalos, Ph.D., an adjunct associate professor in the department of Pathology and Laboratory Medicine in the Perelman School of Medicine at Penn, is co-first author on the study.
The current study builds on Grupp's ongoing collaboration with Penn Medicine scientists who originally developed the modified T cells as a treatment for B-cell leukemias. The Penn team reported on early successful results of a trial using this cell therapy in three adult chronic lymphocytic leukemia (CLL) patients in August of 2011. Two of those patients remain in remission more than 2 years following their treatment, and as the Penn researchers reported in December 2012 at the annual meeting of the American Society of Hematology, seven out of ten adult patients treated at that point responded to the therapy. The team is led by the current study's senior author, Carl H. June, M.D., the Richard W. Vague Professor in Immunotherapy in the department of Pathology and Laboratory Medicine and the Perelman School of Medicine at the University of Pennsylvania and director of Translational Research in Penn's Abramson Cancer Center.
"We're hopeful that our efforts to treat patients with these personalized cellular therapies will reduce or even replace the need for bone marrow transplants, which carry a high mortality risk and require long hospitalizations," June said. "In the long run, if the treatment is effective in these late-stage patients, we would like to explore using it up front, and perhaps arrive at a point where leukemia can be treated without chemotherapy."
The research team colleagues adapted the original CLL treatment to combat another B-cell leukemia: ALL, which is the most common childhood cancer. After decades of research, oncologists can currently cure 85 percent of children with ALL. Both children in the current study had a high-risk type of ALL that stubbornly resists conventional treatments.
The new study used a relatively new approach in cancer treatment: immunotherapy, which manipulates the immune system to increase its cancer-fighting capabilities. Here the researchers engineered T cells to selectively kill another type of immune cell called B cells, which had become cancerous.
T cells are the workhorses of the immune system, recognizing and attacking invading disease cells. However, cancer cells fly under the radar of immune surveillance, evading detection by T cells. The new approach custom-designs T cells to "see" and attack the cancer cells.
The researchers removed some of each patient's own T cells and modified them in the laboratory to create a type of CAR (chimeric antigen receptor) cell called a CTL019 cell. These cells are designed to attack a protein called CD19 that occurs only on the surface of certain B cells.
By creating an antibody that recognizes CD19 and then connecting that antibody to T cells, the researchers created in CTL019 cells a sort of guided missile that locks in on and kills B cells, thereby attacking B-cell leukemia. After being returned to the patient's body, the CTL019 cells multiply a thousand times over and circulate throughout the body. Importantly, they persist for months afterward, guarding against a recurrence of this specific type of leukemia.
While the CTL019 cells eliminate leukemia, they also can generate an overactive immune response, called a cytokine release syndrome, involving dangerously high fever, low blood pressure, and other side effects. This complication was especially severe in Emily, and her hospital team needed to provide her with treatments that rapidly relieved the treatment-related symptoms by blunting the immune overresponse, while still preserving the modified T cells' anti-leukemia activity.
"The comprehensive testing plan that we have put in place to study patients' blood and bone marrow while they're undergoing this therapy is allowing us to be able to follow how the T cells are behaving in patients in real time, and guides us to be able to design more detailed and specific experiments to answer critical questions that come up from our studies," Kalos said.
The CTL019 therapy eliminates all B cells that carry the CD19 cell receptor: healthy cells as well as those with leukemia. Patients can live without B cells, although they require regular replacement infusions of immunoglobulin, which can be given at home, to perform the immune function normally provided by B cells.
The research team continues to refine their approach using this new technology and explore reasons why some patients may not respond to the therapy or may experience a recurrence of their disease. Grupp said the appearance of the CD19-negative leukemia cells in the second child may have resulted from her prior treatments. Unlike Emily, the second patient had received an umbilical cord cell transplant from a matched donor, so her engineered T cells were derived from her donor (transplanted) cells, with no additional side effects. Oncologists had previously treated her with blinatumomab, a monoclonal antibody, in hopes of fighting the cancer. The prior treatments may have selectively favored a population of CD19-negative T cells.
"The emergence of tumor cells that no longer contain the target protein suggests that in particular patients with high-risk ALL, we may need to broaden the treatment to include additional T cells that may go after additional targets," added Grupp. "However, the initial results with this immune-based approach are encouraging, and may later even be developed into treatments for other types of cancer."
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Funding from the National Institutes of Health (grants 1RO1 CA165206, R01 CA102646 and R01 CA116660), the Leukemia and Lymphoma Society, and the Alliance for Cancer Gene Therapy supported this study.
In August 2012, the University of Pennsylvania and Novartis announced an exclusive global research and licensing agreement to further study and commercialize these novel cellular immunotherapies using chimeric antigen receptor (CAR) technologies. As part of the transaction, Novartis acquired exclusive rights from Penn to CART-19, the therapy that was the subject of this clinical trial and which is now known as CTL019.
"Chimeric Antigen Receptor-Modified T Cells for Acute Lymphoid Leukemia," New England Journal of Medicine, Online First, March 25, 2013. To appear in print April 18, 2013.
About The Children's Hospital of Philadelphia:
The Children's Hospital of Philadelphia was founded in 1855 as the nation's first pediatric hospital. Through its long-standing commitment to providing exceptional patient care, training new generations of pediatric healthcare professionals and pioneering major research initiatives, Children's Hospital has fostered many discoveries that have benefited children worldwide. Its pediatric research program is among the largest in the country, ranking third in National Institutes of Health funding. In addition, its unique family-centered care and public service programs have brought the 516-bed hospital recognition as a leading advocate for children and adolescents. For more information, visit http://www.chop.edu.
About Penn Medicine:
Penn Medicine is one of the world's leading academic medical centers, dedicated to the related missions of medical education, biomedical research, and excellence in patient care. Penn Medicine consists of the Raymond and Ruth Perelman School of Medicine at the University of Pennsylvania (founded in 1765 as the nation's first medical school) and the University of Pennsylvania Health System, which together form a $4.3 billion enterprise.
The Perelman School of Medicine has been ranked among the top five medical schools in the United States for the past 16 years, according to U.S. News & World Report's survey of research-oriented medical schools. The School is consistently among the nation's top recipients of funding from the National Institutes of Health, with $398 million awarded in the 2012 fiscal year.
The University of Pennsylvania Health System's patient care facilities include:
The Hospital of the University of Pennsylvania -- recognized as one of the nation's top "Honor Roll" hospitals by U.S. News & World Report; Penn Presbyterian Medical Center; and Pennsylvania Hospital -- the nation's first hospital, founded in 1751. Penn Medicine also includes additional patient care facilities and services throughout the Philadelphia region.
Penn Medicine is committed to improving lives and health through a variety of community-based programs and activities. In fiscal year 2012, Penn Medicine provided $827 million to benefit our community.
A Joint Press Release from The Children's Hospital of Philadelphia and the Perelman School of Medicine at the University of Pennsylvania
Contacts:
Rachel Salis-Silverman
The Children's Hospital of Philadelphia
Phone: 267-426-6063 Salis@email.chop.edu
Holly Auer
Perelman School of Medicine, University of Pennsylvania
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Public release date: 27-Mar-2013
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