FDA approves Roche's Tamiflu for infants with new flu symptoms

The U.S. Food and Drug Administration on Friday expanded the use of Tamiflu, the flu drug from Roche, to children as young as two weeks old who have shown flu symptoms for no more than two days.
The FDA said the drug cannot be used to prevent flu infection in this age group. The drug is currently approved as both a flu treatment and preventative flu drug for children ages 1 and older, and adults. It aims to help lessen the length and severity of the flu.
Tamiflu was approved in 1999 and is distributed in the United States by Genentech, part of Roche. It was co-developed by Gilead Sciences. Its most common side effects include vomiting and diarrhea.
The FDA said its expanded use is based on extrapolating data from previous study results in adults and older children, and supporting studies by the U.S. National Institutes of Health and Roche.
Tamiflu, which had peak sales of $3 billion in 2009 because of the H1N1 swine flu epidemic, is approved by regulators worldwide but some researchers claim there is little evidence it works and have asked Roche to hand over data so they can study its effectiveness.

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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 54th 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.3
These 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.4
Cell-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.5
The 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.6
Therapeutic 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.
Literature
1Kirkwood JM, Butterfield LH, Tarhini AA, Zarour H, Kalinski P, Ferrone S: Immunotherapy of cancer in 2012. CA Cancer J Clin. 2012
2June CH, Blazar BR: T-Cell Infusions: A New Tool for Transfusion Medicine That Has Come of Age. Presentation at 54th ASH Annual Meeting 2013
3Porter DL, Levine BL, Kalos M, Bagg A, and June CH: Chimeric Antigen Receptor-Modified T Cells in Chronic Lymphoid Leukemia. N Engl J Med 2011
4Mellman I, Coukos G, Dranoff G: Cancer immunotherapy comes of age. Nature. 2011
Petsch 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. 2000
6Petsch 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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Allergies, extra weight tied to bullying

 Kids who have food allergies or are overweight may be especially likely to get bullied by their peers, two new studies suggest.
Not surprisingly, researchers also found targets of bullying were more distressed and anxious and had a worse quality of life, in general, than those who weren't picked on.
Bullying has become a concern among parents, doctors and school administrators since research and news stories emerged linking bullying - including online "cyberbullying" - with depression and even suicide.
"There has been a shift and people are more and more recognizing that bullying has real consequences, it's not just something to be making jokes about," said Dr. Mark Schuster, chief of general pediatrics at Boston Children's Hospital and a professor at Harvard Medical School, who wrote a commentary published with the new research.
Studies suggest between one in ten and one in three of all kids and teens are bullied - but those figures may vary by location and demographics, researchers noted.
The new findings come from two studies published Monday in the journal Pediatrics.
In one, Dr. Eyal Shemesh from the Mount Sinai Medical Center in New York and his colleagues surveyed 251 kids who were seen at an allergy clinic and their parents. The children were all between age eight and 17 with a diagnosed food allergy.
Just over 45 percent of them said they'd been bullied or harassed for any reason, and 32 percent reported being bullied because of their allergy in particular.
"Our finding is entirely consistently with what you find with children with a disability," Shemesh told Reuters Health.
A food allergy, he said, "is a vulnerability that can be very easily exploited, so of course it will be exploited."
The kids in the study were mostly white and well-off, the researcher said - a group that you'd expect would be targeted less often. So bullying may be more common in poorer and minority children who also have food allergies.
But allergies aren't the only cause of teasing and harassment by peers.
In another study, researchers from Yale University in New Haven, Connecticut, found that almost two-thirds of 361 teens enrolled in weight-loss camps had been bullied due to their size.
That likelihood increased with weight, so that the heaviest kids had almost a 100 percent chance of being bullied, Rebecca Puhl and her colleagues found. Verbal teasing was the most common form of bullying, but more than half of bullied kids reported getting taunted online or through texts and emails as well.
'START THE CONVERSATION'
Shemesh's team found only about half of parents knew when their food-allergic child was being bullied, and kids tended to be better off when their families were aware of the problem.
He said parents should feel comfortable asking kids if they're being bothered at school or elsewhere - and that even if it only happens once, bullying shouldn't be ignored.
"We want parents to know," he said. "Start the conversation."
"Parents whose kids have a food allergy should really be aware that their kids have the kind of characteristic that often leads to being bullied," Schuster told Reuters Health. "They should be working with the school to handle the food allergy in a way that isn't going to make it more likely that their kids will be bullied - and they need to be attuned to their kids."
That's the same for parents of overweight and obese children, he added.
"Kids need their parents to be their allies in these situations," he said. "Their parents can help them still feel strong.

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12 Weeks is a Long Time to Wait for Breast Cancer Chemotherapy

FIRST PERSON | How long a wait is too long when it comes to treatment of breast cancer? A report published in the Dec. 19 issue of JNCI, Journal of the National Cancer Institute, states that after examining records from 6,622 women, the average time for a woman to wait for adjuvant chemotherapy (chemo given after surgery) for breast cancer is 12 weeks. After my surgery, I waited four weeks before chemotherapy began.
Reconstruction delays
A main cause for delays in starting chemotherapy after surgery was immediate reconstruction. Flap surgeries allow for immediate breast reconstruction. This type of surgery requires a long recuperation period. Chemotherapy impedes healing. All incisions must be healed and all drains removed before chemotherapy can start.
I chose breast implants for reconstruction. This process was partially started during my mastectomy -- consider it partially immediate reconstruction. A tissue expander was put in after they removed my breast. Recovery time is significantly less than with flap surgery. I still had some stitches in when chemo started.
Testing and imaging delays
Testing such as 21-gene reverse-transcription polymerase chain reaction assay testing and MRIs increased the time frame from lumpectomy or mastectomy to the start of chemotherapy. Some doctors use post-surgical MRIs to determine if clear margins were reached. If they are unhappy with the results of the MRI, a second surgery may be required, thus increasing the time before chemo can start.
My oncologist did not feel that any further testing other than a MUGA scan was necessary following my mastectomy. The MUGA scan was performed in order to check heart function before starting on treatment with a monoclonal antibody. Even though I had to go through this imaging, it did not delay the start of chemotherapy.
Other delays
One of the biggest causes of delays in starting chemotherapy treatment in minority women was access to health insurance. Black women who received Medicaid had the longest wait between surgery and the start of chemotherapy when compared to white women with private insurance. This is something that needs to change. When dealing with breast cancer, the faster and more aggressively it is treated, the better the prognosis for survival. There is no reason a woman should have to wait for treatment just because the government is paying for the chemotherapy.
Twelve weeks is too long to wait to start chemotherapy after surgery. Imaging should not have an impact on how long a person waits for chemo. Waiting too long, especially with aggressive forms of breast cancer could be the difference between life and death. I had imaging and started chemo just four weeks after my mastectomy. My outcome might have been very different had I been forced to wait an additional eight weeks before I started chemotherapy.

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New Genetic Tests Determines Breast Cancer and Ovarian Cancer Risks

COMMENTARY | New research has uncovered that mutations in the PPM1D gene is associated with an increased risk of breast cancer and ovarian cancer. Unlike BRCA1 and BRCA2 mutations, the PPM1D mutation is not inherited. Instead, the mutation only shows up in the blood when breast cancer or ovarian cancer is present. Medical News Today quotes professor Nazneen Raham assaying, "This is one of our most interesting and exciting discoveries."

Important discovery

PPM1D mutations are very important. Because of the way they show up in the blood, if you have this mutation you have a 1 in 5 chance of developing breast cancer or ovarian cancer. That is almost twice the average risk for breast cancer and it is 10 times the risk for ovarian cancer. Knowing if you carry this mutation will help women decide on imaging and other preventative treatments. Right now, the only genetic test we have is the BRCA test. As PPM1D shows, BRCA is not the only gene mutation that indicates and increased risk for breast or ovarian cancers.

The study

Unlike many recent studies that have so few participants it makes the data questionable, this study looked at 7,781 women with either breast cancer or ovarian cancer and compared the PPM1D gene to 5,861 women from the general population. This allows the results to be statistically significant because they looked at so many different results. What the study showed is that in the group of women who had  cancer, the researchers found 25 faults in the PPM1D gene. In the group of women without cancer only one fault was found. From a statistical standpoint, those results are quite amazing.

This study proves that newer, more detailed gene sequencing is needed to help determine cancer risks. This is especially true for ovarian cancers, sometimes called the silent killer, because most times this type of cancer is not caught until very late stages. Women with a family history of breast cancer or ovarian cancer need more weapons for detection in their arsenal. BRCA testing alone does not cut it. In my case, I have a family history of cancer but no identified genetic issues, like BRCA. I wonder how many lives testing for PPM1D could save.

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Koomkin.com the new b2b marketplace that connects companies throughout all the Americas

Looking to the global trends, American companies will have to look more and more south of the border for qualified suppliers. Koomkin is already helping companies do that: Enrique Suarez Romo co-founder of the Mexican portal.

Mexico City (PRWEB) December 20, 2012
Ancient Mayans are not just responsible of writing prophecies about the end of the world while drinking hot chocolate; actually they were very good scientists and traders. Honoring this legacy, a group of Mexican entrepreneurs took a Mayan word, Koomkin (that means “to shorten”) to name their new online marketplace. This name was taken in order to bring together a group of new online tools for companies with the purpose of giving all registered firms better web visibility, increase competitiveness and create more business opportunities.
In Mexico, the number of Internet users has been significantly increasing every year, however, many Mexican companies are still reluctant to use the Web to promote their products or services and do business. “We want to provide them with an economic and efficient tool so they can easily show their offer to the world. It is time for Mexican and other Latin American companies to make the most of being now more competitive and cheaper related to their competitors in Asian markets”.
The portal creates an own web page with contact information, chat and pictures for those companies that register for free, as well as a program to make online quotations.
Companies that register through paid memberships can enjoy some services that provides them with competitive advantages: statistics in real time, online marketing campaigns in order to facilitate companies to be identified by search engines, and also the possibility of obtaining a quality certificate with Applus, a business group of certifiers present in more than 40 countries.
The certification gives confidence not only to the companies that offer their products and services in the Koomkin platform, but also to those who are looking for qualified suppliers, increasing exportation and competitiveness.
“We estimate we will be able to have near 37 thousand registered companies basically in Mexico and gradually in the United States (through an alliance with Free Trade Alliance, a San Antonio based organization with a renowned expertise in global trade), Spain and Latin America-, among those around 500 will have a paid membership” Enrique Suarez Romo, co-founder of the Mexican platform that started operating in September, explained. Besides Suarez, the founders of Koomkin are Pablo Garcia (who conceived the idea of the platform), Santiago Miranda and Daniel Alvarez.
Finally the co-founders of Koomkin reported that the companies that dedicate time and resources to digital media get one cost quotation per week, while by being registered at Koomkin they can get up to 300% more than they could get by their own means.

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Fox Web Creations Presents the New World Trade Center Kansas City Website

Web Design in Kansas City is a little more global today with the release of the World Trade Center Kansas City Website, chock-full of great information for international businesses.

(PRWEB) December 20, 2012
Fox Web Creations and The World Trade Center Kansas City have launched a new website - http://www.wtc-kc.com/. Designed for companies already doing business globally, as well as those considering entering the global marketplace, the site boasts resources on everything from the paperwork involved in international business to options for visiting the countries in question.
With experience and operations in Switzerland, Morocco, and France already under their belt, the Kansas City based Web Design firm Fox Web Creations was an excellent partner for this project. CEO and Lead Developer ElAmri "Red" Rida has a personal understanding of the importance of international business and worked closely with the WTC-KC staff to develop the new site. “We wanted the site to be easy to navigate, interactive and helpful to the business community. We also wanted to make sure that the staff of the WTC would be able to easily manage the content themselves, allowing them more freedom to make decisions about their content." Fox Web Creations focuses on web design in Kansas City, and on assisting small and large businesses with their internet marketing and development needs.
“The new site offers everything from help with export documentation and lead generation, to trade data, visits and education,” says Mehgan Flynn, Director of the WTC-KC. “We’re also part of the largest trade network in the world – you’ll find World Trade Centers in 330 cities and 100 countries around the planet. The new website ties into our mission to connect the KC region to the people, data, companies and government agencies that make up the fabric of global commerce.”
Some of the New Website features include:

    A comprehensive calendar of international events in the local community, including:
--    International market briefings

--     International business workshops

--     Intercultural sensitivity workshops

--     Group Trade missions

    ECertify – an easy, online app for Certificates of Origin
    SphereAccess – lead generation for buyers and suppliers.
As a member of the World Trade Center Association (WTCA), WTC-KC can also offer additional resources and services to support the business community in reaching out to international markets. The services include:

    Global market research
    Trade lead identification
    Global trade intelligence
    Intercultural communication training
    International liaison programs
    Discounted access to SphereAccess - a retail buyers and suppliers matchmaking system.
“Now that the new site is launched, we’re gearing up for a new year of WTC-KC programs and services,” says Flynn. “We’ll continue our popular ‘Doing Business In…” programs featuring various countries – China, for one. And, based on a survey of our members, will be offering a series of cultural sensitivity sessions starting this April. We’re also working with the state of Missouri on an intense, three-month export training program for local businesses. So the new year looks pretty full!”
The World Trade Center Kansas City is a partnership of the Greater Kansas City Chamber, the Kansas City Area Development Council, and KCSmartport. Fox Web Creations is a full service Kansas City Web Design, Marketing, Search Engine Optimization (SEO/M), and Responsive Web Design (RWD) firm, located at 4345 State Line Road, in Kansas City, MO 64111. They are dedicated to assisting all businesses, regardless of size, with their web design and development needs.

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Top Realtor in Gainesville VA, Linton Hall Realtors, Launches Interactive Web Experience

A top performing realtor in Gainesville, VA - Linton Hall Realtors - is pleased to announce the launch of an interactive live chat system to aid their website visitors, who are looking to buy or sell homes in the Gainesville, VA area. The addition of the interactive service will allow for expanded real estate client service in an increasingly competitive marketplace.

Gainesville, VA (PRWEB) December 20, 2012
Linton Hall Realtors, one of the highest producing realtors in Gainesville, VA, is pleased to announce the launch of an interactive system to allow real time communications with website visitors. The system will be used to help prospective home buyers search the Gainesville, VA home listings on Linton Hall Realtor's company website. By offering a live chat solution, Linton Hall Realtors expects to help sellers get information they need about listing a home, aid home buyers in finding the right home in the right area, and lead to greater levels of client satisfaction.
Finding homes for sale in Gainesville, VA can be a daunting task. From the Piedmont community in the north down the entire length of Linton Hall Road neighborhoods and communities are springing up. Even as new developments are emerging, some of the older areas are now 15 years old or more. This makes for an area where many families are upgrading and moving within the same community. This is when sellers frequently begin looking for a local agent representative.
Listing a home includes many dynamics. Listing price, marketing the home, and even staging and curb appeal are all important considerations. By implementing the live chat system on the website, people selling their home in Gainesville, VA will be able to interact with a real estate professional right at the moment they begin looking for information. "By providing this type of real time information, we can make the home selling process much easier," said Ashley Leigh, founder of Linton Hall Realtors. "The live chat feature allows us to get critical information to home sellers quickly and easily," he added. Indeed, with programs like the Guaranteed Sale Program, the Move Up to Savings program and even specialized help with short sales, there is a huge quantity of information.
Although there is so much to learn and investigate when selling your home, most sellers conduct extensive research when they are planning to buy new home. Searching for new homes in Gainesville VA is often the more exciting part of the process. That's another reason why Linton Hall Realtors implemented the live chat website feature. "The first thing a buyer/seller does is start searching for their new house. By providing them information when they first begin their search, we can make the entire process work better and smoother," Leigh said. Questions about are schools, planned expansion; home builders and community amenities are all popular questions.
When a user comes to LintonHallRealtors.com, they typically start browsing for a new home and then examining all the program information available to sellers. This process usually continues for weeks or months. When an agent is right there, available for quick questions or even more detailed phone consultations, the home buyer/seller gets exactly the information he or she needs, right at the moment in time it is needed. This leads to an overall improved client experience. "By providing excellent information with real-time technology, we can begin our work with them much earlier in the sales cycle and create a better overall client experience," said Leigh.

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Mission Impossible?: Can Tom Cruise Launch a Box-Office Franchise with 'Jack Reacher'?

LOS ANGELES (TheWrap.com) - Paramount hopes it's launching a franchise with "Jack Reacher," the Tom Cruise action thriller that hits theaters Friday.
It will be tricky in a crowded holiday marketplace, and Cruise isn't the box-office bonanza he once was. But one need only look back to last year's "Mission: Impossible - Ghost Protocol" to see how it might work. That film opened to $12 million on December 16 and went on to make $209 million and nearly $700 million worldwide for Paramount.
"Jack Reacher" will be in about 3,200 theaters, and it will have plenty of competition. Universal's Judd Apatow comedy "This Is 40" opens wide Friday, and Paramount's ‘Guilt Trip" and Disney's 3D re-release of "Monsters Inc." opened Wednesday.
A slew of limited releases, led by Kathryn Bigelow's "Zero Dark Thirty," along with this year's winner of the Palme d'Or at Cannes "Amour," and tsunami survival tale "The Impossible" are also competing for moviegoers' attention, along with a number of holdover hits.
No movie, though, will come close to catching reigning box-office champ "The Hobbit: An Unexpected Journey," which remains in more than 4,000 theaters. Peter Jackson's latest Middle-earth epic will take in north of $40 million, industry analysts say, with "Jack Reacher" and "This Is 40" battling for second with less than half of that.
Warner Bros.' "Hobbit" has rolled to $106 million in the U.S. since opening to $85 million last weekend. Its international total - $188 million as of Thursday - is even bigger.
In "Jack Reacher," Cruise plays an ex-military investigator; the film is based on bestselling author Lee Child's novel "One Shot" and written for the screen and directed by Christopher McQuarrie. It's from David Ellison's Paramount-based Skydance Productions and was produced for about $60 million by Cruise, Don Granger, Paula Wagner and Gary Levinsohn.
Robert Duvall and Richard Jenkins co-star in the PG-13 crime thriller, which has a 53 percent positive rating at Movie Review Intelligence.
No is expecting "Jack Reacher" to match "MI:4" at the box office. The Reacher novels have a following, but nowhere near that of the "Mission Impossible" franchise. Cruise's recent box-office record has been uneven, and the film's Facebook and Twitter activity is not particularly strong.
"Jack Reacher" could wind up playing more like Cruise's "Knight and Day," which opened to $20 million and went on to make $76 million for Fox in 2010, or "Valkyrie," which did $83 million in 2008 after opening to $21 million. Cruise was critically lauded for his foray earlier this year as an aging rock icon in the musical "Rock of Ages," but that was one of the year's bigger box-office duds.
"Jack Reacher" should play strongly with action fans, but Cruise's personal problems could limit its broader appeal.
"I can't imagine his divorce from Katie Holmes and the custody battle hasn't hurt him some with women," BoxOffice.com vice president and chief analyst Phil Contrino told TheWrap Thursday. "Actions fans will come out, but going beyond that demographic is going to be tough for him."
On the other hand, Universal says that it tracking suggests "This Is 40" will do quite well with women -- and women over 25 in particular.
"This Is 40," is, as the marketing campaign points out, a "sort of sequel" to Apatow's "Knocked Up," which opened to $30 million and went on to make nearly $150 million five years ago. Like "This Is 40," that one was written and directed by Apatow and starred Paul Rudd and Leslie Mann.
"40" is the fourth film Apatow has directed, all for Universal ("Funny People" and "40-Year-Old Virgin" are the other two). The ensemble cast also features Albert Brooks, John Lithgow, Megan Fox, Maude Apatow, Iris Apatow, Chris O'Dowd, Jason Segel, Melissa McCarthy and Lena Dunham.
It's R-rated and has a 62 percent positive rating at Movie Review Intelligence. The production budget was $35 million.
"This looks like the strongest comedy of the season," Jeff Bock, senior analyst at Exhibitor Relations told TheWrap, "but it's still a bit of a wild card. It's going to connect with the New York and L.A. crowds; the key will be whether the Heartland audiences embrace it or see it as a little too hip. It will take time to tell, because of the season."
Films released at this time of year tend to open lower because the marketplace is so crowded - by Friday, 11 new films will have hit opened this week - and the fact that many potential moviegoers are districted by shopping and other holiday preps. On the other hand, they often show lasting power and make up what they don't take in on the weekend with stronger showings on the weekdays.
"Things could well come in lower than people are expecting across the board this weekend," Bock said, "but look for many of these movies to make it up over the holidays."
Summit will be looking for that kind of slow build on "The Impossible," the English-language film from Spain based on a true story about a family's fight to survive the 2004 tsunami in Thailand. Ewan McGregor and Naomi Watts, who received a Best Actress nomination from SAG recently, star.
Summit is releasing it Friday in 15 theaters in New York, Los Angeles, Chicago, Philadelphia, Phoenix, San Francisco, Washington, D.C., and Toronto. The plan is to go nationwide early next year.
"The Impossible" already has taken in $52 million in Spain, the home of the real-life couple upon whom the story is based as well as director Juan Antonio Bayona ("The Orphanage") and screenwriter Sergio Sanchez.
Other limited rollouts set for Friday include Paramount's 3D concert film "Cirque du Soleil: Worlds Away," in 800 theaters; "On the Road," IFC Films' adaptation of the Jack Kerouac's beat generation novel, in four theaters; and "Not Fade Away," the Paramount Vantage tale of a group of 1960 New Jersey friends launching a rock band, written and directed by "Sopranos" creator David Chase, in three locations.
Sony's "Zero Dark Thirty," about the manhunt for Osama bin Laden, got off to a terrific start Wednesday. It racked up $124,848 from five theaters in its first day of release. That's an average of $24,969, making it one of the biggest limited mid-week openings in history.

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ReferralBuzz Announces Partnership with TruliaTwin Cities’ Referral Service for Home Remodeling Experts and Their Customers Partners with Leading Online Real Estate Market

Twin Cities’ referral service for home remodeling experts and their customers partners with leading online real estate marketplace.

Minneapolis, MN (PRWEB) December 21, 2012
Starting in January 2013, ReferralBuzz Inc., in Minneapolis, will be the exclusive partner in the 7 county Twin Cities metro and St Cloud, MN, Madison, WI, Cedar Rapids, IA for the new "Find a Pro - Home Improvement" feature on Trulia. Trulia is a leading online marketplace for home buyers, sellers, renters, and real estate professionals. ReferralBuzz will be the first home improvement recommendation resource on the Trulia website.
Founded in 2011, ReferralBuzz gives consumers a free, easy way to find great service providers - including providers who’ve earned recommendations from social media, neighbors, and friends. ReferralBuzz also gives home remodeling experts the tools they need to market their services and increase referrals using the power of social media.
With unique info on areas people want to live that can’t be found anywhere else, Trulia provides the inside scoop on properties, places, and real estate professionals. Prospective home buyers, sellers, and renters can learn about agents, neighborhoods, schools, crime, commute times, and even ask the local community questions. Meanwhile, real estate professionals use Trulia to connect with millions of transaction-ready buyers and sellers each month via Trulia’s hyper-local advertising services, social recommendations, and top-rated mobile real estate apps.
"The partnership with Trulia will provide a huge benefit to our customers through greater exposure,” says ReferralBuzz Founder Lisa Schneegans. “We will be able to feed information onto the "find a pro" section of Trulia's website from the ReferralBuzz website and provide the inside scoop to homeowners, buyers and sellers on local home improvement service providers."
For ReferralBuzz Service Providers, the partnership with Trulia means:

Service Provider’s ReferralBuzz profile will be seen by hundreds of thousands of consumers interested in home improvement in your service area.
Service Providers ReferralBuzz subscription will include a Trulia "Find A Pro" listing that will be automatically be uploaded from your ReferralBuzz profile.
Referral Buzz Service Providers will be able to participate in Trulia Voices "Ask an Expert"
ReferralBuzz will have the exclusive banner ad on the new Trulia mobile app for our metro area. Subsequently giving the service provider’s profile an opportunity to be seen by thousands of people.
How It Works for Homeowners

To get started, homeowners simply sign on at http://www.referralbuzz.com. Homeowners can view exclusive deals, request estimates and get ideas for their own projects from other customers’ pictures and feedback. Homeowners can sign in through Facebook and see which providers their “Friends” have used and recommend.
How It Works For Service Providers

ReferralBuzz provides a set of very easy to use tools for service providers to help them enhance their business. Automated tools include:
Social Referrals-Get customer referrals through their social networks, the “word of mouth” in the digital age.
Customer Feedback-After a job is completed ReferralBuzz makes the request for feedback automatically.
Stay In Touch Email-This in-touch e-mail system turns great customers into repeat customers and helps customers keep you in mind.
Facebook Posting-Automatically post your projects, photos and specials on your own Facebook page.
Digital Portfolio-Keep your visual assets at your fingertips. Photos sell your service better than any sales pitch. Email your presentation to the prospect, right from your IPad.
Project Communication-Communication during a project is often the key to keeping a job on track. ReferalBuzz makes that easy. And, once the project is done, an automated sequence of feedback requests, social referrals and emails begins. Clients feel well taken care of, long after you’ve left the job site.

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