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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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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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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Kenya police: 28 people killed in clashes

NAIROBI, Kenya (AP) — A police official says 28 people have been killed in clashes between farmers and herders in south-eastern Kenya.

Anthony Kamitu, who is leading police operations to prevent the attacks, said Friday that the Pokomo tribe of farmers raided a village of the Orma herding community, called Kipao, at dawn in the Tana River Delta.

The latest deaths in a tit-for-tat cycle of killings may be related to a redrawing of political boundaries and next year’s general elections, according to the U.N.

At least 110 people were killed in clashes between the Pokomo and Orma in September and October.

Animosity between the two communities over land and water resources has existed for decades.

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Moroccan road film subverts Hollywood stereotypes

DUBAI (Reuters) – When director John Slattery first visited Morocco, the familiarity was jarring – and as removed from the images of an exotic Orient conjured up by Hollywood as possible.

That dichotomy between the representation and the reality of Morocco drives Slattery‘s charming paean to a country he clearly loves and makes “Casablanca, Mon Amour” a thoughtful rejoinder to U.S. popular culture.

Two young Moroccans spend three weeks travelling their native country, filming what they see on a digital camera while passing by studios and locations that have formed the backdrop for many Hollywood blockbusters, an industry Morocco has cultivated.

The film is spliced with shots of endearingly bemused or nervous ordinary people giving their thoughts to the camera about Hollywood and its global stars, as well as clips from classics such as “Casablanca” featuring off-the-cuff anti-Arab slurs like “you can’t trust them” and “they all look alike”.

“We had the idea of going on this trip and to be this stupid American film crew going to make this traditional movie using Morocco, but we wanted to subvert that,” Slattery said after a screening at the Dubai international film festival this week.

“There was not really a script but the trip was their trip and so wherever they went we followed them. So that way they were really directing the film.”

Shot by Hassan, who narrates the road trip in French, the images shift from scenes of daily life caught on camera, to his comically testy relationship with his travelling companion Abdel, to a troupe they stumble upon in Meknes that plays traditional Moroccan “malhoun” music.

Hassan, a real-life film school student at the time, is using the road trip for a class project, while Abdel wants to visit a dying uncle on the other side of the country.

Slattery includes footage from Moroccan television from the Marrakech film festival in which comic actor Bashar Skeirej declares that “a country without its own art will never have a history”.

It’s a subtle suggestion that the government should do more to promote domestic film rather than just rent out landscapes for Hollywood misrepresentation.

Morocco has formed the backdrop for a fictionalized Orient in “Ishtar”, doubled as Abu Dhabi in the “Sex in the City 2″ and been various distant planets in Star Wars films.

“National cinemas in many countries are being destroyed or have been destroyed because of this massive power of marketing that is Hollywood,” said Slattery, a California-based American of Irish origin. “They destroy little films, they destroy the possibility for little stories.”

The film, a labor of love that took Slattery seven years to complete, borrows from the book “Reel Bad Arabs”, author Jack Shaheen’s study of Hollywood’s anti-Arab stereotypes. Its title references Alain Resnais’s 1959 French New Wave classic “Hiroshima, Mon Amour”.

“(When) I would say ‘Morocco’, people would say ‘were you scared’, or a polite ‘what was that like?’,” Slattery said, recounting reactions in the United States when he would talk about his first experiences as a peace corps volunteer.

“There was that whole category of fear in the responses, or ‘Morocco, you must have seen Lawrence of Arabia’, or ‘Blackhawk Down’! – all these film titles. That stuck with me, this fear and movies were the two references for Morocco.”

Yet Slattery‘s first day in the North African country could not have been more mundane, he said.

A colleague whisked him off to a rural home near Rabat where he met farmers who reminded him of Ireland.

“This guy opens (his door) in a tweed jacket that was all torn up. This is how these old farmers dress in Ireland, and his hands were all calloused and dirty. It just felt very familiar to me,” Slattery said.

“His grandmother had a television hooked up to a car battery for electricity. I spent the weekend there, hanging out with these people, cutting hay and stuff, and I just thought ‘this is Ireland’.”

(Editing by Paul Casciato)

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Resolve to Get Clearer Skin in the New Year– Tips From the Paula’s Choice Research Team

It’s frustrating, but true: Acne, to one degree or another, can occur at any age. The Paula’s Choice Research Team behind the best-selling book, Don’t Go to the Cosmetics Counter Without Me, share the facts and products they’ve uncovered to have acne-free skin at any age.

Seattle, Washington (PRWEB) December 21, 2012

Let 2013 be a year where skin is beautiful and clear—because, while it’s frustrating, it is true: Acne can strike at any age and at any time. Whether it’s during the teen years or in the middle of menopause, acne affects up to 95% of the population at various stages of life. It’s a struggle that the Paula’s Choice Research Team, writers of the best-selling book, Don’t Go to the Cosmetics Counter Without Me, know all too well.

Through their investigative work evaluating and reviewing all kinds of skin-care products, as well as published research on acne and its treatments, they developed this essential guide to having clear skin at any age.

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      Cleanse Twice Daily: Use a gentle, water-soluble cleanser to remove excess oil and makeup that lead to clogged pores and dull-looking skin. Drying cleansers will cause irritation, making acne worse. Try Paula’s Choice CLEAR Normalizing Cleanser, a face wash that’s tough on blemishes but gentle on skin.

  
  


•     Leave-On Exfoliant is a Must: Daily use of a well-formulated, leave-on product with salicylic acid (also known as beta hydroxy acid, or BHA) works beautifully to unclog pores that cause breakouts. Salicylic acid also reduces the redness and red marks from acne and provides an additional antibacterial punch. Truly, BHA is an anti-acne miracle! Find the top-rated salicylic acid products on CosmeticsCop.com.


•     Eradicate Acne-Causing Bacteria: After exfoliating, apply a lightweight, nonirritating anti-acne product that’s medicated with benzoyl peroxide. This well-researched topical disinfectant works to quickly eliminate acne-causing bacteria. Apply it to all breakout-prone areas as a preventive measure—don’t just spot-treat current pimples.


•     Avoid Heavy Moisturizers: Those with oily skin and breakouts should not use traditional cream moisturizers, even if they claim to be oil-free, because the ingredients in cream moisturizers can clog pores. Instead, if dry areas are a concern, apply a lightweight, gel-textured moisturizer for soothing relief or opt for a serum, which is especially great to prep skin for makeup.


•     Remove Surface Pimples: Beauty magazines and even some dermatologists say one should never pop a pimple, but let’s get real—sometimes, it’s just plain necessary. In reality, popping a pimple the right way reduces inflammation, scarring, and healing time, and gets rid of the ugly white bump. Follow this step-by-step guide to safely and effectively pop, treat, and conceal a blemish.

These basic tips for clear skin are the first step in the battle against blemishes. For information on how to treat, conceal, and prevent acne visit CosmeticsCop.com.

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Led by best-selling author and beauty expert Paula Begoun, the Paula’s Choice Research Team evaluates and reviews hundreds of skin-care and makeup products, in books such as Don’t Go to the Cosmetics Counter Without Me, and online at CosmeticsCop.com. Combining cosmetics industry knowledge and expertise, Paula and her team have developed the Paula’s Choice line of state-of-the-art formulations based on reliable, published skin-care research. Products include skin-care, makeup, body, and hair-care products, beauty tools, and accessories. All products are fragrance-free, cruelty free, and environmentally friendly, and they perform beautifully without false promises.

Tanya Wayne
[email protected]
212-243-1431
Email Information

Seniors/Aging News Headlines – Yahoo! News

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US budget negotiations setback drives stocks down

PARIS (AP) — A failed attempt find a compromise in U.S. budget negotiations sent global stock markets plummeting Friday, as investors feared the world’s largest economy could teeter into recession if no deal is found.

Without an agreement, the U.S. economy will fall off the so-called “fiscal cliff” on Jan. 1 when Bush-era tax cuts expire and spending cuts kick in automatically. The measures were designed to have a negative effect on the U.S. economy, in the hopes that the feared outcome would push lawmakers and President Barack Obama to find a deal.

“We’ve seen Europe’s politicians repeatedly flirt lemming-like with cliff-diving in 2012, and now it’s the turn of U.S. ‘leaders,’” said Kit Juckes, an analyst with Societe Generale. “The nagging fear is always there that someone, on one side of the Atlantic or the other, will forget to let rational thought take over at the last second.”

Amid the uncertainty, European shares fell. France’s CAC dropped 0.15 percent to 3,661, while the DAX in Germany dropped 0.6 percent at 7,626. The FTSE index of leading British shares retreated 0.6 percent to 5,929.

The euro also fell sharply, dropping 0.3 percent to $ 1.3182.

In Asia, Japan’s Nikkei 225 index closed 1 percent lower at 9,940.06. Hong Kong’s Hang Seng lost 0.7 percent to 22,506.29. South Korea’s Kospi shed 1 percent at 1,980.42. Australia’s S&P/ASX 200 fell 0.2 percent to 4,623.60. Mainland Chinese stocks were mixed.

U.S. stock futures tumbled after rank-and-file Republican lawmakers failed to support an alternative tax plan by House Speaker John Boehner late Thursday in Washington. That plan would have allowed tax rates to rise on households earning $ 1 million and up. Obama wants the level to be $ 400,000.

In early trading in New York, the Dow Jones industrial average dropped 1 percent to 13,183, while the broader Standard & Poor’s index fell 1.1 percent at 1,427.

“The fiscal cliff is a real threat not just for U.S. growth next year but for the outlook for global growth,” said Jane Foley, currency analyst with Rabobank.

When growth slows, energy demand does, too, and oil prices fell in anticipation.

Benchmark crude for February delivery fell $ 1.92 to $ 88.19 per barrel in electronic trading on the New York Mercantile Exchange.

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Pamela Sampson in Bangkok and Fu Ting in Shanghai contributed to this report.

Economy News Headlines – Yahoo! News

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