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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China and India: The $10 Trillion Engine of Future U.S. Growth

My friend and colleague Michael J. Silverstein, writing in this space in late October, mentioned that the most dangerous thing about China is America’s misguided attitude toward the country. In short, we appear to be afraid of China’s success.

The U.S. has never before run from a challenge. This is the wrong time to start.

As Silverstein and his co-authors—Carol Liao, David Michael, and Abheek Singhi—point out in their new book, The $ 10 Trillion Prize, one of the reasons many Americans feel threatened by China is they don’t know a lot about the country. What they do “know,” by and large, is what they’ve been told by politicians and others who accuse China of stealing U.S. jobs.

Yes, many low-skill, low-wage U.S. jobs have moved elsewhere, in many cases to China. Yes, many low-cost, mass-produced products that used to be made here are now being made there, and in other low-cost countries, such as India, Indonesia, Malaysia, Mexico, Thailand, and Vietnam. And, yes, many of those jobs will never come back.

But as China and the other developing countries grow, they also become potential customers for U.S. goods and services, from corn and soybeans to automobiles, commercial jetliners, heavy machinery, construction and farm equipment, and banking, investment, and insurance services, to name just a few.

It wasn’t that long ago that the prevailing American vision of the Middle Kingdom was that of millions of mindless peasants marching in automaton-like lockstep to the orders of the party bosses. They led lives of drudgery, on collective farms, toiling for mere survival. Everybody dressed like Chairman Mao. Dissent was met with tanks. And it wasn’t that long ago that that may have been accurate in some respects.

But China today, as Silverstein and his co-authors make clear, is a booming multiclass society with hundreds of millions of people who want nothing more than their own version of the American Dream: a nice home, a quality car, a good education for their children, appliances and conveniences, better health care, stylish clothes, more time for travel and leisure. In short: a better life for the next generation than the current generation enjoyed. The same is true in India.

The authors visited with and tell the stories of dozens of Chinese and Indian families and entrepreneurs who are striving for the same things Americans want—and for the first time in their lives, they have the money to get them.

My colleagues have calculated that between 2010 and 2020, Chinese and Indian consumers will spend some $ 64 trillion on goods and services. Chinese consumers will spend approximately $ 41.5 trillion, with annual expenditures reaching more than $ 6 trillion in 2020. Indians will spend $ 22.5 trillion, with annual spending hitting an estimated $ 3.6 trillion by 2020. Combined, they will be spending some $ 10 trillion per year by 2020—more than three times what they spent in 2010.

That’s what U.S. politicians and business leaders should be talking about: the promise of China and India as engines of future U.S. growth. That’s the prize the book is about.

China and India today show the kind of unbridled optimism that used to be the hallmark of America. Many Chinese and Indian entrepreneurs expect their companies to grow by factors of 10 over the next decade.

Rather than fear such growth, Americans should embrace it, wish them well, and make sure our businesses, farms, and factories are prepared to meet their needs.

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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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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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Vatican says pope beats Justin Bieber on re-tweets

VATICAN CITY (Reuters) – Pope Benedict, white-haired, 85, and a neophyte to social media site Twitter, has beaten out 18-year old heartthrob Justin Bieber to set a percentage record for re-tweeting by his followers, the Vatican said on Thursday.

The Vatican newspaper said that as of noon Italian time on Thursday the pope had 2.1 million followers on Twitter, eight days after his first tweet was sent.

While Canadian singer-songwriter Bieber has roughly 15 times as many followers – 31.7 million – the Vatican newspaper said Benedict had beaten Bieber on re-tweets.

It said about 50 percent of the pope’s followers had re-tweeted his first tweet on December 12 while only 0.7 percent of Bieber’s followers had re-tweeted one of the singer’s most popular tweets on September 26, when he commented on the death by cancer of a six-year-old fan.

The Vatican said this was part of a wider trend in which people were looking for more spiritual content.

The pope already tweets in English, German, Italian, French, Spanish, Portuguese, Polish and Arabic. The newspaper said he will start tweeting in Latin and Chinese soon.

(Reporting By Philip Pullella, editing by Paul Casciato)

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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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Can Nepal’s Republic Be Saved?

If you were a politician in Nepal during the past two years, there’s some chance you may have been slapped. In January 2011—as well as in May and November of this year—three citizens who were fed up with chronic government inaction physically attacked three senior politicians.

Nepal’s citizens survived 10 years of a bloody Maoist insurrection that killed an estimated 16,000 people but also brought about the end of a centuries-old monarchy in 2008. Since then, however, the country has been hampered by chronic political and economic crises that have created a severe legitimacy crisis for the ruling elites. Can this nascent republic be saved?

It seems to be an impossible challenge in the near term. The current political crisis is so dire that there has been no parliament since May. In November, hints surfaced of a presidential coup to oust the Maoist-led caretaker government of Prime Minister Baburam Bhattarai. President Ram Baran Yadav heard advice from the military chief and the Indian ambassador about the best way out of the crisis, but he ultimately took no action. Weeks later, the political crisis persists.

On Nov. 29, Prime Minister Bhatterai and various political factions failed to meet the president’s deadline to form a national unity government that would lead to parliamentary elections for April or May. On Dec. 6, the factions failed again to meet the extended deadline. A day later, on Dec. 7, President Yadav offered yet another six-day extension. But the ruling alliance of the Unified Communist Party of Nepal (Maoist) and United Democratic Joint Madhesi Front, as well as the opposition Nepali Congress and Communist Party of Nepal, failed to select a prime ministerial candidate, missing the latest deadline. Amid such political deadlock, there has been no progress on a new constitution—a critical component of the peace deal that ended the Maoist civil war in the first place.

This political crisis has amplified the economic weaknesses of the aid-dependent country, a quarter of whose population lives below the poverty line. Youth unemployment is over 40 percent and job creation is a struggle, especially with growth expected to drop to 3.8 percent in 2012-13, from 4.5 percent the previous year, according to the International Monetary Fund. The approval of the government’s budget on Nov. 21 averted a major financial crisis that would have left half a million civil servants, soldiers, and police without pay. This was a rare spot of good news for the dysfunctional country.

Though India and China already have significant stakes in their neighbor, the political crisis puts further foreign investment in jeopardy. One report suggests that Nepal’s diplomats have secured additional investment abroad, but this is contingent on the establishment of a constitution and the return of political stability. Other potential investors, including many businessmen from Saudi Arabia, have admitted losing interest in Nepal because of the political impasse. The country’s dismal ranking of 141 (out of 176 countries) on Transparency International’s Corruption Perceptions Index, the recurring power crisis, and additional structural limitations are not helping matters.

If the political and economic situation continues to stagnate, and no constitution is finalized to unite the people, it is likely that ethnic and religious differences—as well as the frustrations of historically marginalized groups from lower castes—will serve as significant sources of conflict.

It’s clear that the ruling elites are rapidly losing domestic legitimacy. Unfortunately, this has not motivated them to resolve the political crisis with dispatch. Perhaps it’s time for foreign donors to apply overt pressure on Nepal by making future aid conditional on a resolution to the political deadlock.

Even if a political consensus emerges as to how to move forward, it will take time before Nepal’s rulers regain the legitimacy needed to allow the government to ease the economic crisis. If no consensus is reached in 2013, mass street protests—which in the past brought down the monarchy—are likely to resurface. The way things are going, another Nepali politician could get slapped.

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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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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)

Canada News Headlines – Yahoo! News

Title Post: Showrooming little threat to clothiers in ho-hum holidays
Rating:
100%

based on 99998 ratings.
5 user reviews.
Author: Fluser SeoLink
Thanks for visiting the blog, If any criticism and suggestions please leave a comment

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