Cancer Immunotherapy Where Are We Going?

The compelling concept of utilizing the patient’s own immune system for a stronger and more effective way to attack cancer cells is not a new one. William Coley observed in 1891 that infections produced in patients with inoperable cancer following an injection of streptococcal organisms (Gram-positive bacteria) led to tumor shrinkage especially when the patients developed fever and other signs of a full-blown infection.¹ Since then, research has embraced approaches to “train” the patient’s own immune system to recognize certain biomarkers or proteins that are mainly found on cancer cells and to destroy the cells.

After several setbacks the first cellular immunotherapy, Dendreon’s Sipuleucel-T (Provenge^(R)), was approved for the treatment of prostate cancer in 2010. Today, new promising cancer immunotherapy approaches are in clinical trials. Most recently, researchers at the 54^th American Society of Hematology (ASH) meeting reported early success with a developmental-stage cell-based cancer vaccine for the treatment of leukemia and have shown remission in several patients ^2,3, including a 7-year old girl who relapsed twice after chemotherapy.Cancer immunotherapy can be thought of as either active or passive immunotherapy. The most prominent passive immunotherapies, which have revolutionized cancer therapy, are monoclonal antibodies that either target tumor-specific antigens and receptors or block important pathways central to tumor growth and survival. Therapeutic monoclonal antibodies are the market leader in the targeted cancer therapy space and include blockbusters such as trastuzumab (Herceptin^(R)) or rituximab (Rituxan^(R)).In general, antibodies are significant elements of the body’s adaptive immune system. They play a dominant role in the recognition of foreign antigens and the stimulation of the immune response. Therapeutic antibodies target and bind to antigens, usually proteins that are mainly expressed on diseased cells such as cancer cells. After binding, cancer cells can be destroyed by different mechanisms such as antibody-dependent cellular cytotoxicity, the activation of the complement system — an important part of the immune system — and triggering cell death.Although very successful, especially in oncology, therapeutic antibodies have a significant limitation: they don’t generate a memory response by the immune system, and thus, repeated antibody infusions are required. Further, monoclonal antibodies are only able to recognize specific proteins present of the cell surface. Monoclonal antibodies are mostly produced in cell culture systems which are often costly. Humanization of murine monoclonal antibodies by replacing of certain parts of the antibody with human sequences has improved the tolerability of antibodies and made them less immunogenic, but even fully human sequence-derived antibodies can carry some immunological risk.Novel approaches in the passive immunization strategy include antibody drug conjugates, a combination of targeting antibody with a very potent drug such as the recently approved brentuximab vedotin (ADCETRIS(TM)) for Hodgkin lymphoma and anaplastic large cell lymphoma (ALCL). ADCETRIS comprises an anti-CD30 monoclonal antibodyanti-CD30 monoclonal antibody and a cytotoxic (cell-killing) agent that is released upon internalization into CD30-expressing tumor cells. Currently, the development of next generations of ADCs is underway.Alternatively, specific and durable cancer immunotherapies designed to actively “train” or stimulate the patient’s intrinsic immune response have been more problematic; however, recent success stories, such as the cell-based immunotherapy Provenge, have revitalized this field. Dendreon’s approach modifies the patients’ own dendritic cells to present a protein specific to prostate cancer cells.Dendritic cells are the most potent, “professional” antigen-presenting cells. They process the antigen material and present it on their surface to other cells of the immune system. Once activated, the dendritic cells migrate to the lymphoid tissues where they interact with T-cells and B-cells — white blood cells and important components of the immune system — to initiate and shape the adaptive immune response. To develop Provenge, each patient’s own dendritic cells are harvested and then loaded ex vivo with the tumor-associated antigen. Now “presenting” the antigen, the dendritic cells are administered back into the patient to induce a potent, cell-mediated anticancer immune response resulting in tumor shrinkage and clinical benefit.In another experimental approach for the treatment of leukemia, patients’ own modified T-cells were infused back into the patients. Prior to this, the T-cells were transduced with a lentivirus to express the CD19-specific chimeric antigen receptor. CD19 is an antigen which is found on B-cell neoplasms, cancerous B-cells, and the lentivirus was the vehicle to transfer the genetic material for CD19 into the cells. A case report published in the New England Journal of Medicine stated that a patient with chronic lymphocytic leukemia (CLL) was in ongoing remission 10 months after treatment.³These promising results have spurred continued research for new and safe ways to achieve effective tumor vaccination, and drug developers have explored many cancer immunotherapy strategies. To generate an effective antitumor immunity, therapeutic intervention should drive several functions; specifically, it should promote the antigen presentation functions of dendritic cells, promote the production of protective T-cell responses, stimulate B-cells and overcome immunosuppression characteristics that are common to tumor cells.⁴Cell-based therapeutic vaccines are most frequently produced outside the patient’s body and involve isolation of the specific cells, such as dendritic cells, and the introduction of preselected antigens, often with the use of specific vehicle, into the cells. The antigens can be encoded in viral vectors (frequently DNA) or administered as peptides or proteins in a suitable adjuvant and carrier through a long and cumbersome process.During my doctoral thesis, I conducted immunization experiments using RNA as a negative control, assuming that the RNA would be degraded during the experiment thus making it impossible to use as a vaccine. The physiological role of messenger (m) RNA is to transfer genetic information from the nucleus to the cytoplasm where this information is translated into the corresponding protein. mRNA is known to be very unstable and has a relatively short half-life. But astonishingly, we were able to measure a solid T-cell immune response. We repeated the experiment and confirmed that the RNA we had produced had the potential to be used as a vaccine. Importantly, we didn’t need to isolate the patients’ cells: mRNA-based vaccines can be injected directly into the skin (intradermal). The mRNA-based vaccines are then taken up by antigen-presenting cells, such as dendritic cells, and are then able to induce an immune response. Importantly, mRNA-vaccines can also be synthesized quickly for any antigen sequence identified.⁵The first mRNA-based vaccines (RNActive(R)) are now in the clinic for the treatment of prostate cancer and lung cancer and have demonstrated that they do what they are supposed to do – induce a balanced humoral, as well as T cell-mediated, immune response that is entirely HLA independent. The HLA (human leukocyte antigen) system is used to differentiate the body’s own cells (self) and non-self cells. Additionally, RNA-vaccines do not need a vehicle such as a virus for delivery to the cells, nor do they contain virus-derived elements that are often found in DNA-vaccines. These attributes make RNActive a very safe therapeutic.The risk of integration of the RNA into the host-genome is minimized (RNA would have been transcribed first to DNA, and then it has to be transported to the nucleus), as is the residual risk of DNA-based vaccines for inactivating or activating genes or affecting cellular regulatory elements, which can induce oncogenesis. Thus, the favorable safety profile of mRNA-based therapies broadens their potential use not only for the treatment of diseases but for use as prophylactic vaccinations. A recent proof-of-concept study using mRNA-based vaccines (RNActive) in animal models for influenza was published in Nature Biotechnology.⁶Therapeutic cancer immunotherapies and vaccines have come a long way, and novel, promising approaches give hope for safe and effective treatment options. This may one day lead to the treatment of all cancers as chronic diseases.Literature¹Kirkwood JM, Butterfield LH, Tarhini AA, Zarour H, Kalinski P, Ferrone S: Immunotherapy of cancer in 2012. CA Cancer J Clin. 2012²June CH, Blazar BR: T-Cell Infusions: A New Tool for Transfusion Medicine That Has Come of Age. Presentation at 54^th ASH Annual Meeting 2013³Porter DL, Levine BL, Kalos M, Bagg A, and June CH: Chimeric Antigen Receptor-Modified T Cells in Chronic Lymphoid Leukemia. N Engl J Med 2011⁴Mellman I, Coukos G, Dranoff G: Cancer immunotherapy comes of age. Nature. 2011Petsch B, Schnee M, Vogel AB, Lange E, Hoffmann B, Voss D, Schlake T, Thess A, Kallen KJ,⁵Hoerr I, Obst R, Rammensee HG, Jung G: In vivo application of RNA leads to induction of specific cytotoxic T lymphocytes and antibodies. Eur J Immunol. 2000⁶Petsch B, Schnee M, Vogel AB, Lange E, Hoffmann B, Voss D, Schlake T, Thess A, Kallen KJ, Stitz L, Kramps T: Protective efficacy of in vitro synthesized, specific mRNA vaccines against influenza A virus infection. Nat Biotechnol. 2012 

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Anti-tax conservatives say no to tax-increase deal

BOSTON (AP) — In the city where a protest over tax policy sparked a revolution, modern day tea party activists are cheering the recent Republican revolt in Washington that embarrassed House Speaker John Boehner and pushed the country closer to a "fiscal cliff" that forces tax increases and massive spending cuts on virtually every American.

"I want conservatives to stay strong," says Christine Morabito, president of the Greater Boston Tea Party. "Sometimes things have to get a lot worse before they get better."

Anti-tax conservatives from every corner of the nation echo her sentiment.

In more than a dozen interviews with The Associated Press, activists said they would rather fall off the cliff than agree to a compromise that includes tax increases for any Americans, no matter how high their income. They dismiss economists' warnings that the automatic tax increases and deep spending cuts set to take effect Jan. 1 could trigger a fresh recession, and they overlook the fact that most people would see their taxes increase if President Barack Obama and Boehner, R-Ohio, fail to reach a year-end agreement.

The strong opposition among tea party activists and Republican leaders from New Hampshire to Wyoming and South Carolina highlights divisions within the GOP as well as the challenge that Obama and Boehner face in trying to get a deal done.

On Capitol Hill, some Republicans worry about the practical and political implications should the GOP block a compromise designed to avoid tax increases for most Americans and cut the nation's deficit.

"It weakens the entire Republican Party, the Republican majority," Rep. Steven LaTourette, R-Ohio, said Thursday night shortly after rank-and-file Republicans rejected Boehner's "Plan B" — a measure that would have prevented tax increases on all Americans but million-dollar earners.

"I mean it's the continuing dumbing down of the Republican Party and we are going to be seen more and more as a bunch of extremists that can't even get a majority of our own people to support policies that we're putting forward," LaTourette said. "If you're not a governing majority, you're not going to be a majority very long."

It's a concern that does not seem to resonate with conservatives such as tea party activist Frank Smith of Cheyenne, Wyo. He cheered Boehner's failure as a victory for anti-tax conservatives and a setback for Obama, just six weeks after the president won re-election on a promise to cut the deficit in part by raising taxes on incomes exceeding $250,000.

Smith said his "hat's off" to those Republicans in Congress who rejected their own leader's plan.

"Let's go over the cliff and see what's on the other side," the blacksmith said. "On the other side" are tax increases for most Americans, not just the top earners, though that point seemed lost on Smith, who added: "We have a day of reckoning coming, whether it's next week or next year. Sooner or later the chickens are coming home to roost. Let's let them roost next week."

It's not just tea party activists who want Republicans in Washington to stand firm.

In conservative states such as South Carolina and Louisiana, party leaders are encouraging members of their congressional delegations to oppose any deal that includes tax increases. Elected officials from those states have little political incentive to cooperate with the Democratic president, given that most of their constituents voted for Obama's Republican opponent, Mitt Romney.

"If it takes us going off a cliff to convince people we're in a mess, then so be it," South Carolina GOP Chairman Chad Connelly said. "We have a president who is a whiner. He has done nothing but blame President Bush. It's time to make President Obama own this economy."

In Louisiana, state GOP Chairman Roger Villere said that "people are frustrated with Speaker Boehner. They hear people run as conservatives, run against tax hikes. They want them to keep their word."

Jack Kimball, a former New Hampshire GOP chairman, said he was "elated" that conservatives thwarted Boehner. He called the looming deadline a political creation. "The Republicans really need to stand on their principles. They have to hold firm."

Conservative opposition to compromise with Obama does not reflect the view of most Americans, according to recent public opinion polls.

A CBS News survey conducted this month found that 81 percent of adults wanted Republicans in Congress to compromise in the current budget negotiations to get a deal done rather than "stick to their positions even if it means not coming to an agreement." The vast majority of Republicans and independent voters agreed.

Overall, 47 percent in the poll said they blamed Republicans in Congress more than Obama and Democrats for recent "difficulties in reaching agreements and passing legislation in Congress." About one-quarter placed more blame on the Democrats and 21 percent said both were responsible.

Although negotiations broke down last week, Obama still hopes to broker a larger debt-reduction deal that includes tax increases on high earners and Republican-favored cuts to entitlement programs such as Medicare and Social Security. If a compromise continues to prove elusive, lawmakers could pass a temporary extension that delays the cliff's most onerous provisions and gives Congress more time to work out a longer-term solution.

That's becoming the favored path by some Republicans leery of going over the cliff.

Mississippi Republican Chairman Joe Nosef shares his Southern colleagues' disdain for tax increases. But he stopped short of taking an absolute position.

"I really, really feel like the only way that Republicans can mess up badly is if they come away with nothing on spending or something that's the same old thing where they hope a Congress in 10 years will have the intestinal fortitude to do it," he said.

Matt Kibbe, president of the national organization and tea party ally, FreedomWorks, says that going over the cliff would be "a fiscal disaster." He says "the only rational thing to do" is approve a temporary extension that prevents widespread tax increases.

But his message doesn't seem to resonate with conservative activists in the states.

"If we have to endure the pain of the cliff then so be it," said Mark Anders, a Republican committeeman for Washington state's Lewis County. "While it may spell the end of the Republican Party ... at least we will force the government to cut and cut deep into actual spending."

Back where the Boston Tea Party protest took place in 1773, Morabito wonders whether Boehner will survive the internal political upheaval and says Republicans need to unite against Obama.

"It looked like from the very beginning they were just going to cave to what President Obama wanted," she said of the GOP. "I didn't want that to happen. Now I'm hopeful that they're standing up for taxpaying Americans."

___

Associated Press writers Bill Barrow in Atlanta, Rachel La Corte and Michael Baker in Washington state, Thomas Beaumont in Iowa, and AP Director of Polling Jennifer Agiesta in Washington contributed to this report.

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Nick Cassavetes Sued For Allegedly Stiffing Twin Canadian Pop Duo on $300K Movie Loan

LOS ANGELES (TheWrap.com) – Nick Cassavetes, Canadian twins and incest – besides three phrases that you probably didn’t expect to read in the same sentence today, they’re also elements of a bizarre new lawsuit that hit the California court system this week.

In a lawsuit filed Tuesday in Los Angeles Superior Court, TwinSpin music – home to twin Canadian pop duo Carmen & Camille – claim that “The Notebook” director failed to pay back a $ 300,000 loan to help make the upcoming drama “Yellow.”

The complaint alleges that the writer-director backed out of an agreement to give the duo parts in the movie and to feature a song of theirs in the Sienna Miller-Ray Liotta film.

The film chronicles a woman who’s addicted to pain pills and is fired from her teaching job for engaging in sexual shenanigans on school grounds. Oh, and she also had a love affair with her brother at one point. According to the suit – which also includes TwinSpin manager John Thomas as a plaintiff – TwinSpin and Cassavetes entered into an agreement in September 2010, in which TwinSpin would loan Cassavetes $ 300,000 to start production on the film.

In return, the suit says, Cassavetes agreed to pay the loan back with interest – for a total of $ 345,000 – the next month. Cassavetes also agreed to cast the duo in speaking roles in the film, use a song of theirs on the soundtrack, and to give Thomas a producer’s credit, the complaint claims.

But the money never came, the suit says – and neither did the roles, the song and the credit, without which the loan never would have been given.

“But for these representations, Plaintiffs never would have entered into the Loan Agreement or otherwise granted the Loan,” the lawsuit reads. “Plaintiffs are informed and believe that Cassavetes never had any intention of casting ‘Carmen & Camille’ in the Picture, or featuring a song by ‘Carmen & Camille’ in the Picture, of providing the producer credit to plaintiff Thomas, or of repaying the loan on a timely basis.”

Cassavetes’ agent has not yet responded to misrepresentation request for comment.

Alleging breach of contract, breach of covenant of good faith and fair dealing, fraudulent misrepresentation and negligent misrepresentation, the suit is asking for damages of $ 500,000, the amount that the plaintiffs believe is currently owed to them by Cassavetes, with accruing interest.

(Pamela Chelin contributed to this report)

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Anti-tax conservatives say no to tax-increase deal

BOSTON (AP) — In the city where a protest over tax policy sparked a revolution, modern day tea party activists are cheering the recent Republican revolt in Washington that embarrassed House Speaker John Boehner and pushed the country closer to a "fiscal cliff" that forces tax increases and massive spending cuts on virtually every American.

"I want conservatives to stay strong," says Christine Morabito, president of the Greater Boston Tea Party. "Sometimes things have to get a lot worse before they get better."

Anti-tax conservatives from every corner of the nation echo her sentiment.

In more than a dozen interviews with The Associated Press, activists said they would rather fall off the cliff than agree to a compromise that includes tax increases for any Americans, no matter how high their income. They dismiss economists' warnings that the automatic tax increases and deep spending cuts set to take effect Jan. 1 could trigger a fresh recession, and they overlook the fact that most people would see their taxes increase if President Barack Obama and Boehner, R-Ohio, fail to reach a year-end agreement.

The strong opposition among tea party activists and Republican leaders from New Hampshire to Wyoming and South Carolina highlights divisions within the GOP as well as the challenge that Obama and Boehner face in trying to get a deal done.

On Capitol Hill, some Republicans worry about the practical and political implications should the GOP block a compromise designed to avoid tax increases for most Americans and cut the nation's deficit.

"It weakens the entire Republican Party, the Republican majority," Rep. Steven LaTourette, R-Ohio, said Thursday night shortly after rank-and-file Republicans rejected Boehner's "Plan B" — a measure that would have prevented tax increases on all Americans but million-dollar earners.

"I mean it's the continuing dumbing down of the Republican Party and we are going to be seen more and more as a bunch of extremists that can't even get a majority of our own people to support policies that we're putting forward," LaTourette said. "If you're not a governing majority, you're not going to be a majority very long."

It's a concern that does not seem to resonate with conservatives such as tea party activist Frank Smith of Cheyenne, Wyo. He cheered Boehner's failure as a victory for anti-tax conservatives and a setback for Obama, just six weeks after the president won re-election on a promise to cut the deficit in part by raising taxes on incomes exceeding $250,000.

Smith said his "hat's off" to those Republicans in Congress who rejected their own leader's plan.

"Let's go over the cliff and see what's on the other side," the blacksmith said. "On the other side" are tax increases for most Americans, not just the top earners, though that point seemed lost on Smith, who added: "We have a day of reckoning coming, whether it's next week or next year. Sooner or later the chickens are coming home to roost. Let's let them roost next week."

It's not just tea party activists who want Republicans in Washington to stand firm.

In conservative states such as South Carolina and Louisiana, party leaders are encouraging members of their congressional delegations to oppose any deal that includes tax increases. Elected officials from those states have little political incentive to cooperate with the Democratic president, given that most of their constituents voted for Obama's Republican opponent, Mitt Romney.

"If it takes us going off a cliff to convince people we're in a mess, then so be it," South Carolina GOP Chairman Chad Connelly said. "We have a president who is a whiner. He has done nothing but blame President Bush. It's time to make President Obama own this economy."

In Louisiana, state GOP Chairman Roger Villere said that "people are frustrated with Speaker Boehner. They hear people run as conservatives, run against tax hikes. They want them to keep their word."

Jack Kimball, a former New Hampshire GOP chairman, said he was "elated" that conservatives thwarted Boehner. He called the looming deadline a political creation. "The Republicans really need to stand on their principles. They have to hold firm."

Conservative opposition to compromise with Obama does not reflect the view of most Americans, according to recent public opinion polls.

A CBS News survey conducted this month found that 81 percent of adults wanted Republicans in Congress to compromise in the current budget negotiations to get a deal done rather than "stick to their positions even if it means not coming to an agreement." The vast majority of Republicans and independent voters agreed.

Overall, 47 percent in the poll said they blamed Republicans in Congress more than Obama and Democrats for recent "difficulties in reaching agreements and passing legislation in Congress." About one-quarter placed more blame on the Democrats and 21 percent said both were responsible.

Although negotiations broke down last week, Obama still hopes to broker a larger debt-reduction deal that includes tax increases on high earners and Republican-favored cuts to entitlement programs such as Medicare and Social Security. If a compromise continues to prove elusive, lawmakers could pass a temporary extension that delays the cliff's most onerous provisions and gives Congress more time to work out a longer-term solution.

That's becoming the favored path by some Republicans leery of going over the cliff.

Mississippi Republican Chairman Joe Nosef shares his Southern colleagues' disdain for tax increases. But he stopped short of taking an absolute position.

"I really, really feel like the only way that Republicans can mess up badly is if they come away with nothing on spending or something that's the same old thing where they hope a Congress in 10 years will have the intestinal fortitude to do it," he said.

Matt Kibbe, president of the national organization and tea party ally, FreedomWorks, says that going over the cliff would be "a fiscal disaster." He says "the only rational thing to do" is approve a temporary extension that prevents widespread tax increases.

But his message doesn't seem to resonate with conservative activists in the states.

"If we have to endure the pain of the cliff then so be it," said Mark Anders, a Republican committeeman for Washington state's Lewis County. "While it may spell the end of the Republican Party ... at least we will force the government to cut and cut deep into actual spending."

Back where the Boston Tea Party protest took place in 1773, Morabito wonders whether Boehner will survive the internal political upheaval and says Republicans need to unite against Obama.

"It looked like from the very beginning they were just going to cave to what President Obama wanted," she said of the GOP. "I didn't want that to happen. Now I'm hopeful that they're standing up for taxpaying Americans."

___

Associated Press writers Bill Barrow in Atlanta, Rachel La Corte and Michael Baker in Washington state, Thomas Beaumont in Iowa, and AP Director of Polling Jennifer Agiesta in Washington contributed to this report.

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Meanwhile, Deep Inside Your Belly Button …

Dec 23, 2012 7:00am

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Reported by Dr. Amish Patel:

Researchers have found that more than 2,000 different species of bacteria live in our umbilicus – the medical word for belly button.  That means you have more kinds of bacteria in your belly button than there are different kinds of ants or birds in North America, according to the study.

The majority of these bacteria were rare and occurred in just one individual.  No single type was common to all 60 belly buttons sampled.

“I don’t find it alarming,” said Dr. William Schaffner, an expert in infectious diseases at Vanderbilt University Medical Center in Nashville, Tenn.  “We knew belly buttons weren’t sterile.”

However, Schaffner believes that this does not minimize the study’s findings.

“This is in the context of a much larger study, which is trying to … get greater insight into the source of pathogens and how the [bacteria on our body] changes with antimicrobial therapy and age.”

Perhaps, he said, we can “use this to develop new antimicrobials.”

The benefits may extend beyond antibiotics.

“Understanding the biodiversity of our bodies and how it differs among people may play an important role in understanding why some … people are susceptible to the same pathogen or respond to the same drug or diet,” said Dr. Rob Knight, associate professor of molecular biophysics at the University of Colorado – Boulder.

Although the findings of the study do not have any immediate implications, this is good timing for a public service announcement from Dr. Gregory Poland, infectious disease expert at the Mayo Clinic in Rochester, Minn.

“The current fad of women piercing their umbilicus has led to many case reports of infections,” Poland said. “And with today’s multiple drug-resistant bacteria, it can lead to disasters.”

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News summary: Nintendo’s TVii replaces the remote

TVii LAUNCH: Nintendo if flipping on its TVii service Thursday, a month after sales started for its Wii U game console. The service turns the GamePad controller into a TV remote control, channel guide and Web video surfer.

SALES HOPES: Nintendo hopes the free service boosts sales of the console after recording 425,000 sales in the first week since its Nov. 18 launch.

HEAD START: It’s the first time a game console maker has put live TV controls into a device, but analyst Michael Pachter says competitors will copy the function soon.

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3-day trip becomes 3-week ordeal for 2 Jamaicans

SAN JUAN, Puerto Rico (AP) — It was supposed to be a three-day fishing trip at most. It turned into a three-week ordeal, drifting under an intense sun for hundreds of miles in the Caribbean in a small boat with a broken motor.

The two Jamaican fishermen survived by eating raw fish they caught and drinking water from melted ice they had brought to preserve their catch. The Colombian navy finally plucked them from the sea a week ago and delivered them home Saturday after treating them for severe dehydration, malnutrition and hypothermia.

Everton Gregory, 54, and John Sobah, 58, recounted their story in a telephone interview from Jamaica, while the boat owner and the men’s employer also provided details.

The men set off from Jamaica’s southeastern coast on Nov. 20. The water was glassy, the wind was calm and their boat was laden with 14 buckets of ice, 16 gallons of water and several bags of cereal, bread and fruit.

They headed to Finger Bank, a nearby sand spit 8-miles-long (13-kilometers) that is known for its abundance of fish like wahoo, tuna and mahi mahi. The owner of the 28-foot (8-meter) boat said she usually joins them on fishing trips, but she couldn’t go that afternoon.

After spending a couple of days around Finger Bank, the two men set off for home with their catch. But the boat’s engine soon died. The water was too deep to use the anchor and the current too strong to use the oars, so the boat slowly drifted away from Jamaica.

At first, the men got by on sipping the water and eating the food they brought with them. But days turned into weeks, and they began to eat the fish they had caught and drink the melted ice that had kept it fresh.

Gregory and Sobah kept eating raw fish and used a tarp to try to collect water, but the rain clouds remained at a distance.

Back home, friends and family called police and used their own boats to search the area where the men were last seen. The two fishermen work for the Florida-based nonprofit group Food for the Poor, which chartered a plane to search along Jamaica’s coast.

Marva Espuet, the owner of the boat, said she knew she had packed it with more food and water than needed for a three-day trip, but the thought provided little relief.

“If I had gone, there would have been two boats going,” said the 52-year-old woman, a longtime friend of both fishermen.

With searches proving fruitless, Sobah’s niece grew frantic, recalled Nakhle Hado, a fishing manager for Food for the Poor who helped lead the search. She “begged me that she wanted John back for Christmas,” Hado said.

Hado said some people believed the two men would never be found, but he and others didn’t give up. “My gut was telling me that they were still alive,” he said.

Hado said he had trained Gregory and Sobah on how to survive at sea.

“In case something happens, they don’t have to think twice. They know how to react,” he said. “It’s very important, their mental state.”

Gregory and Sobah finally ran out of fresh water and went several days without drink. A healthy human being can die from dehydration anywhere from three to five days without water.

Then on Dec. 12, a Colombian navy helicopter patrolling off the coast of that South American country spotted the men near Lack of Sleep cay, more than 500 miles (800 kilometers) from where they started. It took two days for a navy vessel to reach them because of bad weather. The men were hospitalized for several days at the Colombian island of San Andres before boarding a plane back home to Jamaica.

“It feels good,” Sobah told the AP in a brief phone interview after arriving.

Gregory said he had lost hope, but Sobah tried to keep him positive that they would be rescued. “I just had that belief,” Sobah said. “I believe in the Creator.”

Yet it is Gregory who plans to keep fishing despite the ordeal because he needs the job.

Sobah said he’s done. “I’m not going to go fishing again. No way.”

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Showrooming little threat to clothiers in ho-hum holidays

Chicago (Reuters) – In retail, showrooming has not hit shirts yet.

Showrooming, the retail term for shoppers who try a product, then buy it cheaper on Amazon.com or other websites, has driven retailers to the point of hiding barcodes, improving their own websites and coming up with methods to get people to complete their purchase in the store.

But brand-name clothing retailers have an advantage over companies that sell items you can buy anywhere, like televisions and home goods.

“Specialty apparel retailers are some of the least affected by showrooming since the more exclusive the product is, the harder it is to showroom,” said Joel Bines, managing director of the retail practice at advisory firm AlixPartners.

That, in turn, has helped retailers like Gap Inc and Lululemon Athletica Inc find favor with investors.

A survey of 2,010 adults conducted by AlixPartners showed consumers who shop for apparel were among the least likely (35 percent) to go to other websites after they liked an item at a store, compared with 42 percent of electronics shoppers and 41 percent of those looking for accessories like watches and jewelry.

“If you look at some of the most successful (clothes) companies in the past few years, they are those that have that moat around them,” said hedge fund manager Shawn Kravetz, who runs Esplanade Capital in Boston.

He cites yogawear maker Lululemon and Gap as good examples of how it can help to have clothes that are not sold elsewhere.

If a shopper wants to buy a Banana Republic or Nordstrom shirt from the latest season, they have to buy it either from their stores or online shop.

Discount retailers like Zappos, Amazon and others stock brand-name products, but the merchandise is often not from the current season or limited in colors and sizes.

“I don’t need to see if a television fits my body shape when I buy a TV,” said Joe Megibow, senior vice president of omni-channel e-commerce at American Eagle Outfitters. The teen clothes retailer has seen better sales than its peers over the past year.

“I can get a sense of the TV and I’m good. Clothing is different. Does it fit me, is it my style, do I like the quality of the material and how it is put together. There’s so much more with apparel that matters,” he said.

That is the part of the reason, analysts say, why online-only clothing companies like Bonobos and Gap’s Piperlime have started opening brick-and-mortar stores or tied up with retailers to sell their products in physical locations.

Choice and easy availability are the two most important aspects of shopping, especially during a holiday season that has lost steam after what looked like strong Thanksgiving sales.

Estelle Tran, an “impulsive” shopper in her twenties, agreed.

“If I want to buy books, tech items, DVDs, I would definitely buy online. For clothes, I would rather (visit stores) as it is also a fun experience to try on clothes,” said the Chicago-based finance auditor.

Tran said she would definitely check prices online if she was spending more than $ 100.

Luxury and high-priced items can be more susceptible to showrooming, because pricing is what drives the behavior, said Marshal Cohen, chief economist at the consultancy NPD Group.

“With electronics and certain consumer goods it is very easy to compare specific brands across multiple websites. But (showrooming is) happening and it will be growing. If a (clothes) retailer isn’t taking it seriously, they are going to fall behind,” said Bolette Andersen, principal in KPMG’s retail industry practice.

ROOM TO GROW

Some investors are betting on apparel stocks because of their relative insulation from the threat of showrooming.

While the S&P Apparel Index has returned a sizzling 27.71 percent year to date, according to Reuters data, far outperforming the S&P 500, which is up 14.80 percent, more gains may be coming.

“We still think there’s plenty of room to grow,” said Brian Peery, co-portfolio manager at Hennessy Funds. Its growth fund, heavily weighted in apparel and consumer discretionary goods shares, is up 30 percent over the year.

“As we look into the sector 12-18 months, we continue to buy the discretionary area. Two of our heaviest investments would be Foot Locker Inc and TJX Companies Inc,” he said.

Discount chains like TJX and Ross Stores, which sell branded clothes at low prices, have benefited from the surge in bargain-seeking shoppers.

Even the stocks of retailers like Gap and American Eagle that have staged or are staging turnarounds have gotten a good boost over the year. Gap has soared 69 percent and American Eagle is up 31 percent.

R. Shawn Neville, president of Avery Dennison retail branding and information solutions, said another reason that apparel and to a broader extent other consumer discretionary stocks do well is because of their sustainability.

“In uncertain times, investors look towards market segments that have strong underlying demand which are more stable, like the apparel industry,” Neville said.

Moreover, in times of economic uncertainty, shoppers can still afford clothes and shoes, as opposed to a new car, home, or expensive vacations, helping apparel stocks do well, he said.

“Though Amazon is clearly stealing some share in various categories, clothes retailers, say Abercrombie & Fitch isn’t going anywhere. They’re not being run out of the shopping mall,” said Esplanade’s Kravetz.

(Editing by Jeffrey Benkoe)

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Hundreds pay tribute to legendary Indian sitarist Ravi Shankar

ENCINITAS, California (Reuters) – Ravi Shankar‘s daughters, Norah Jones and Anoushka Shankar, along with the wife of late Beatle George Harrison said their final goodbyes to the Indian sitar virtuoso on Thursday at a public memorial service in Encinitas, California.

The legendary musician and composer, who helped introduce the sitar to the Western world through his collaboration with The Beatles, died on December 11 in Southern California. He was 92.

About 700 people joined Shankar’s wife, Sukanya, and family at the service held at a spiritual center in the coastal town about 25 miles north of San Diego.

Olivia Harrison, the widow of Beatles guitarist George Harrison, told Reuters the three-time Grammy winner who formed a musical and spiritual bond with The Beatle “expressed music at its deepest level.”

“As a person he was just sweet and seemed to know everything,” she added. “He was a true citizen of the world.”

Shankar is credited with popularizing Indian music through his work with violinist Yehudi Menuhin and The Beatles beginning in the mid-1960s, inspiring George Harrison to learn the sitar and the British band to record songs like “Norwegian Wood” (1965) and “Within You, Without You” (1967).

“He completely transformed (George’s) musical sensibilities,” a tearful Harrison told the crowd. “They exchanged ideas and melodies until their hearts and minds were intertwined like a double helix.”

‘LITTLE CRUMB’

His friendship with Harrison led him to appearances at the Monterey and Woodstock pop festivals in the late 1960s and the 1972 Concert for Bangladesh. He became one of the first Indian musicians to become a household name in the West.

His influence in classical music, including on composer Philip Glass, was just as large. His work with Menuhin on their “West Meets East” albums in the 1960s and 1970s earned them a Grammy, and he wrote concertos for sitar and orchestra for both the London Symphony Orchestra and the New York Philharmonic.

“I always felt like a little crumb in his presence,” Zubin Mehta, a former music director of the New York Philharmonic and collaborator with Shankar, said at the service.

Jazz pianist Herbie Hancock also attended the service along with “Anna Karenina” director Joe Wright, the husband of Shankar’s daughter Anoushka.

Shankar, who had lived in Encinitas for the past 20 years, had suffered from upper respiratory and heart issues over the past year and underwent heart-valve replacement surgery last week at a hospital in San Diego.

The surgery was successful but he was unable to recover.

Shankar’s final concert was on November 4 in Long Beach, California, with his Grammy-winning sitarist daughter Anoushka, who spoke giving thanks to those who came. Jones, the third Grammy-winner in the family, did not speak at the service.

(Writing by Eric Kelsey; editing by Philip Barbara)

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Cliff poses many risks to U.S. public sector, few severe: Moody’s

WASHINGTON (Reuters) – The “fiscal cliff” of impending federal spending cuts and tax increases set for the beginning of the year poses a wide variety of risks to the public sector, but many of the threats hanging over state and local governments are not severe or direct, Moody’s Investors Service said on Thursday.

President Barack Obama and Congressional leaders are in the middle of tough negotiations to avert the cliff before the start of the new year. Economists have warned the combination of tax hikes and across-the-board spending cuts, often referred to as sequestration, could plunge the country back into recession.

A downturn or a downgrade in the U.S. debt rating resulting from the federal budget battles would threaten the credit quality of the public sector, Moody’s said.

“Rating changes could ensue for public finance credits that have direct, or in some cases indirect, linkages to the rating and credit standing of the U.S. government,” it said.

“These rating changes would occur if Moody’s lowers the U.S. government’s rating as a result of the fiscal cliff, or a federal budget agreement is reached that fails to reduce the ratio of federal debt-to-GDP over the medium term,” it added.

Sequestration would mostly impact states indirectly as federal grants to people shrink and they spend less money. Currently, Medicaid, the healthcare program for the poor that states administer with federal reimbursements, is safe from sequestration. Moody’s warned that if Obama and Congress were to decide to cut it in their agreement, “the credit impact would be more severe.”

“The largest component of the sequester is an approximately 9.4 percent, $ 30 billion across-the-board cut to discretionary defense programs,” Moody’s added. “If it is implemented, the economic impact will be most heavily felt in states with high concentrations of defense procurement contracting such as Maryland, New Mexico and Virginia.”

Local governments only receive 5 percent of their revenues from direct federal payments, on average, meaning they too will only be affected by sequestration as lower spending hurts their revenues, Moody’s said. Cities dominated by the federal government and military could be hit harder.

While Medicaid is off limits in sequestration, Medicare, the health insurance program for the elderly, would have to reduce reimbursements for services by 2 percent. That would hit non-profit hospitals.

Sequestration would also cut agencies that fund research at universities, but will likely only impact new grants, while the availability of federal financial aid may shrink, hurting higher education, Moody’s said

The agency also said defense spending cuts will hurt military housing and could negatively impact revenue bonds for it.

(Reporting By Lisa Lambert; Editing by Leslie Adler)

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