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Leading Health Organizations Revise Cervical Cancer Screening Guidelines
Last week, several health organizations issued new cervical cancer screening guidelines that extend the time interval between screening tests for most women.
Based on comprehensive reviews of available data—including NCI-funded research—the new guidelines seek to maximize the benefits of current screening tests while minimizing their potential harms. Read more > >
Smoking Declines Helped Prevent More Lung Cancer Deaths than ExpectedModel estimates 795,000 deaths from lung cancer averted between 1975 and 2000
Study Identifies a Mechanism behind Pancreatic Cancer Treatment ResistanceCombination therapy targeting mechanism is being tested in humans
Expanded Tumor Profiling Yields Clues about Acute Myeloid LeukemiaApproach could inform decisions about treatment
Updated European Prostate Cancer Screening Trial Data Show Little Change in Risk ReductionEstimated relative mortality reduction the same after 2 more years of follow-up
Also in the Journals: Children and Adolescents with Acute Lymphoblastic Leukemia are Living Longer
A Conversation with Dr. Thomas Smith on the Growing Role of Palliative Care for Patients with Cancer
Recent research has shown that some cancer patients who received early palliative care not only had improved quality of life, but lived longer than patients who received standard treatment alone. Dr. Thomas J. Smith, director of palliative care for the Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, talked with the NCI Cancer Bulletin about the growing importance of palliative care in oncology practice.
Surgeon General's Report Finds Youth Smoking Remains a Serious ConcernOne-third of young adults smoke, smokeless tobacco use is up
Mapping the Evolution of Cancer Cells in LeukemiaFindings point to targets for treating form of acute myeloid leukemia
Featured Clinical Trial: Combining Systemic Therapies for Patients with Advanced Liver CancerWill adding chemotherapy to sorafenib improve survival?
CDC Update
- Federal Campaign Seeks to Shrink Smoking Rates Further
- NCI and CICAMS Sign Statement of Intent
- NCI Advisory Committee on Clinical Trials Holds First Meeting of 2012
- NCI at American Association of Cancer Research Annual Meeting
- Dr. John Potter to Deliver First Schatzkin Lecture in Nutritional Epidemiology
- New Complementary and Alternative Medicine Report and Information Posted Online
Selected articles from past issues of the NCI Cancer Bulletin are available in Spanish.
The NCI Cancer Bulletin is produced by the National Cancer Institute (NCI), which was established in 1937. Through basic, clinical, and population-based biomedical research and training, NCI conducts and supports research that will lead to a future in which we can identify the environmental and genetic causes of cancer, prevent cancer before it starts, identify cancers that do develop at the earliest stage, eliminate cancers through innovative treatment interventions, and biologically control those cancers that we cannot eliminate so they become manageable, chronic diseases.
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Featured Article
Leading Health Organizations Revise Cervical Cancer Screening Guidelines
Last week, several health organizations issued new cervical cancer screening guidelines that extend the time interval between screening tests for most women. Based on comprehensive reviews of available data—including NCI-funded research—the new guidelines seek to maximize the benefits of current screening tests while minimizing their potential harms.
The United States Preventive Services Task Force (USPSTF) released one set of guidelines, and a group of three health organizations—the American Cancer Society (ACS), the American Society for Colposcopy and Cervical Pathology (ASCCP), and the American Society for Clinical Pathology (ASCP)—released a second set. Although the two sets of guidelines were developed independently, their recommendations are consistent.
The ACS/ASCCP/ASCP guidelines were published jointly in CA: A Cancer Journal for Clinicians, Journal of Lower Genital Tract Disease, and American Journal of Clinical Pathology on March 15. The USPSTF recommendation statement appeared the same day in the Annals of Internal Medicine.
A better understanding of the role of persistent oncogenic human papillomavirus (HPV) infection in the initiation and progression of cervical cancer, as well as results from numerous studies evaluating the performance of HPV DNA testing in screening, prompted this re-evaluation of cervical cancer screening guidelines.
"These recommendations ensure that women receive the benefits of testing while minimizing the harms," said Dr. Diane Solomon of the Breast and Gynecologic Cancer Research Group in NCI's Division of Cancer Prevention, who helped develop the ACS/ASCCP/ASCP guidelines. "We're screening less often, but we're screening smarter."
The guidelines apply to women who have a cervix, whose immune systems have not been compromised, and who were not exposed in utero to substances such as diethylstilbestrol (DES) that would increase their risk. The recommended intervals are for women with normal test results; those with abnormal test results need to be followed more frequently.
When to Screen
Both sets of guidelines call for screening to start at age 21, regardless of when a woman becomes sexually active. The groups concluded that most HPV infections, which are spread through sexual contact, and cervical changes that are detected before this age will likely resolve on their own and not become cancerous.
The recommendations also extend the time interval between tests. Women ages 21 to 65 should be screened with the Pap test every 3 years. Women ages 30 to 65 who have the HPV DNA test and the Pap test (co-testing) can be screened every 5 years. ACS, ASCCP, and ASCP preferred co-testing over the Pap test alone, whereas the USPSTF deemed co-testing acceptable based on recently published data, including a study of women enrolled in the co-testing program at Kaiser Permanente Northern California, which was conducted in collaboration with NCI researchers. (See "HPV and Pap Co-Testing Safely Extend Cervical Cancer Screening Intervals".)
—Dr. Debbie Saslow
The ACS/ASCCP/ASCP guidelines also provide follow-up recommendations for women who have a positive HPV DNA test result and a normal Pap test result or a negative HPV DNA test result and mildly abnormal Pap test result.
"This is good news for women," said USPSTF Chair Dr. Virginia Moyer, professor of pediatrics at the Baylor College of Medicine, in a press release, "because evidence shows that an annual Pap smear is not necessary to prevent deaths from cervical cancer. Screening every 3 years [with the Pap test] saves the same number of lives as annual screening, but with half the number of colposcopies and fewer false-positive tests."
"Pap tests have been done yearly in the past, but we now know that annual screening is not needed and can lead to harm from treatment of cell changes that would never go on to cause cancer," said Dr. Debbie Saslow, first author of the ACS/ASCCP/ASCP guidelines and director of breast and gynecologic cancer for the ACS, in a statement. "With the addition of the HPV [DNA] test, we can test even less frequently, as the risk of precancer and cancer when both tests are negative is so low."
When Not to Screen
Women who have had a hysterectomy and no longer have a cervix should not be screened, according to the new guidelines. Likewise, women over age 65 should not be screened if they have had three consecutive negative Pap tests or two consecutive negative co-tests within 10 years, and the last test was administered within 5 years. However, women with a history of cervical precancer or a cancer diagnosis should continue screening as recommended by their physician, according to the new guidelines, for at least 20 years, even if it means testing after age 65.
In addition, the guidelines recommend against using the HPV DNA test alone in women of any age or using co-testing in women younger than 30 years of age because, HPV is common in young women, but the vast majority of HPV infections are transient. "HPV testing kicks in as a primary screening tool at age 30 as the prevalence of HPV infection declines and the underlying risk of there being something clinically relevant is higher with a positive HPV result," said Dr. Solomon.
Women who have had a previous diagnosis of cervical cancer or precancer or who are at higher risk for cervical cancer, including women with compromised immune systems or who were exposed to DES before birth, may need more intensive or alternative screening.
Screening Outlook
Whether gynecologists and family physicians will follow the new guidelines remains to be seen and will likely be the subject of future research. "We need to emphasize education," said Dr. Solomon. "As clinicians understand the rationale and the scientific basis behind these recommendations, I think they will be accepted and implemented. But it is going to take some time.
"Decades ago, we did a very good job of inculcating in clinicians' minds and in women's minds that they needed an annual Pap test. And we were so successful that it is hard to move people past that now," Dr. Solomon continued. "Cervical screening is best done using the most sensitive testing strategy at the longest safe interval. This provides safety for women and reduces the 'noise' of over-screening. When you find things that are not really clinically relevant but that need to be worked up, that causes anxiety and needless additional procedures."
Regardless, the authors of both sets of guidelines stressed that the greatest gains in reducing the incidence and mortality of cervical cancer will be attained only by increasing access to screening among women who are unscreened or screened too infrequently.
Cancer Research Highlights
Smoking Declines Helped Prevent More Lung Cancer Deaths than Expected
Reductions in smoking have helped to save more lives from lung cancer than previously thought, an NCI-funded study has found, but many more deaths could have been averted with even greater declines in smoking. In the study, researchers in NCI's Cancer Intervention and Surveillance Modeling Network (CISNET) used computer models to quantify the impact of falling smoking rates on lung cancer mortality in the United States. The findings appeared March 14 in the Journal of the National Cancer Institute.
The researchers modeled three different scenarios: one based on actual smoking behaviors, one in which all smoking ceased following publication of the first Surgeon General's report on smoking and health in 1964, and one in which smoking rates remained at the high levels that existed prior to the report's publication (representing what might have occurred if no tobacco control policies had been implemented).
It was estimated that, on average, 795,000 deaths from lung cancer were averted between 1975 and 2000 due to actual declines in smoking. (This calculation does not include deaths from other forms of cancer or smoking-related diseases.) Had all smoking ceased in 1965—the first full year after the 1964 Surgeon General's Report—2.5 million deaths from lung cancer would have been averted during the same period, a number slightly less than the current population of Chicago.
The estimated mortality reductions are much larger than several earlier studies predicted. "[Our study] was a much more detailed analysis" than had been performed in those earlier studies, explained study co-author Dr. Suresh Moolgavkar of the Fred Hutchinson Cancer Research Center. "We essentially reconstructed smoking histories and the associated lung cancer risks for the entire U.S. population."
The CISNET study "should serve as a model for future analyses in public health more broadly," wrote Dr. Thomas Glynn of the American Cancer Society in an accompanying commentary. The results, he continued, "are tantalizing—especially in the 'what could have been' scenario—but, more important, they give us a clear view to what should be the future of tobacco control in the United States."
The study's findings "show that we've come a long way since the first Surgeon General's report and [have] done a very good job of reducing tobacco use," said study co-author Dr. Eric "Rocky" Feuer of NCI's Division of Cancer Control and Population Sciences. "But they also show that we still have a long way yet to go and cannot relax our efforts."
Study Identifies a Mechanism behind Pancreatic Cancer Treatment Resistance
Researchers have discovered a physical mechanism that prevents chemotherapy from reaching pancreatic cancer cells, as well as a way to reverse that mechanism. Dr. Sunil Hingorani of the Fred Hutchinson Cancer Research Center and his colleagues reported their results March 19 in Cancer Cell.
Pancreatic adenocarcinoma, the most common type of pancreatic cancer, is notoriously resistant to chemotherapy and radiation therapy, leading to an overall 5-year relative survival rate of less than 5 percent. Using mice with tumors that are genetically similar to human pancreatic adenocarcinomas, the researchers found that, as the tumors grow, a thick matrix develops and surrounds the tumors' cells.
The matrix exerts tremendous pressure on the tumors—pressure that greatly exceeds the normal pressure found within blood vessels—causing the tumors' blood vessels to collapse. This collapse prevents chemotherapy drugs in the blood stream from reaching the tumor cells.
Dr. Hingorani and his colleagues identified a substance called hyaluronic acid that forms a large part of this pressurized matrix. When they treated the mice with an enzyme called PEGPH20, which breaks down hyaluronic acid, the pressure within the tumors returned to normal, and the blood vessels regained their normal shape and function.
When the researchers treated mice with a combination of PEGPH20 and the chemotherapy drug gemcitabine, 83 percent of tumors within the pancreas shrank after only one cycle of treatment, and all tumors shrank after three cycles. Similar responses were seen in metastatic tumors. Mice that received the combination therapy survived almost twice as long as mice that received PEGPH20 plus a placebo.
"When able to penetrate the tumor bed, gemcitabine can indeed be an effective agent against this disease," wrote the authors. An early phase clinical trial is testing the combination of PEGPH20 and gemcitabine in people with metastatic pancreatic cancer.
Expanded Tumor Profiling Yields Clues about Acute Myeloid Leukemia
Testing the cancer cells of patients with acute myeloid leukemia (AML) for alterations in a panel of 18 genes could help doctors predict the risk of relapse for individual patients, according to a retrospective analysis of data from a large clinical trial. This approach—sometimes called cancer profiling—could also provide information about which patients may benefit most from certain treatments. The findings appeared in the March 14 New England Journal of Medicine.
Doctors use various methods to diagnose AML and to classify patients according to the risk of relapse. Some patients have their cancers profiled for alterations in three genes associated with AML. The new study suggests, however, that analyzing a larger set of genes could help doctors assign patients to more precise subgroups, with favorable, intermediate, or unfavorable risk profiles.
To reach this conclusion, Dr. Ross Levine of Memorial Sloan-Kettering Cancer Center and his colleagues profiled stored samples from nearly 400 participants in a large clinical trial led by the Eastern Cooperative Oncology Group (ECOG) and published in 2009. The researchers then validated their findings using an independent group of 104 patients from the same trial.
At least one cancer-related genetic alteration was found in 97 percent of the patients. Certain mutations tended to occur together, revealing clues to the pathways that are active in AML, the researchers noted. In addition, the expanded panel yielded better prognostic information than the one currently used in the clinic.
"Some of the newly discovered mutations substantially improved the classification of patients as having either a favorable or unfavorable risk profile," Dr. Levine said.
He noted that profiling cancers may also inform decisions about treatment. Results from the ECOG trial showed that AML patients under 50 years of age may benefit from a higher dose of daunorubicin chemotherapy early in treatment. The new analysis, however, found that some patients benefited more than others.
Specifically, higher-dose daunorubicin chemotherapy improved survival among patients whose cancer cells had DNMT3A or NPM1 gene mutations or MLL gene translocations but not among patients with cancer cells that lacked these gene alterations. These findings need to be confirmed, the authors noted.
Future studies will seek to identify additional genetic and epigenetic events that contribute to AML. "The challenge will be to not look at each alteration as an independent variable, but instead to see whether new alterations—together with other known mutations—improve prognostic models and inform the selection of treatments," Dr. Levine said.
The new study shows what can be learned by analyzing DNA samples and data from a completed clinical trial, noted Dr. Lucy Godley of the University of Chicago Medical Center, who wrote an accompanying editorial. "Dr. Levine essentially took samples from the freezer and used them to ask new questions about AML."
Updated European Prostate Cancer Screening Trial Data Show Little Change in Risk Reduction
After 11 years of follow up, results from a large European clinical trial continue to show a reduced risk of death from prostate cancer associated with prostate specific antigen (PSA) screening. The findings, from the European Randomized Study of Screening for Prostate Cancer (ERSPC) trial, show a 21 percent relative reduction in prostate cancer mortality among men who underwent routine PSA screening compared with men who did not—the same risk reduction previously reported after 9 years of follow-up.
Consistent with the earlier results, screening was also associated with important harms, Dr. Fritz Schröder of Erasmus University Medical Center and his colleagues reported March 15 in the New England Journal of Medicine. About half of those diagnosed on the basis of PSA screening were overdiagnosed—that is, diagnosed with prostate cancers that likely would never have threatened their lives.
Overall, the researchers found that 1,055 men would need to be invited for screening and 37 cancers would need to be detected to prevent one death from prostate cancer.
With approximately 182,000 participants, the eight-country ERSPC trial consortium is the largest randomized study of PSA screening for prostate cancer ever conducted. Earlier this year, 13-year follow-up results were published from the second-largest trial, the NCI-funded Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial of 77,000 men. In the PLCO trial, annual PSA screening did not reduce the risk of dying from prostate cancer. Screening did lead to substantial rates of overdiagnosis but lower than those in the ERSPC trial.
The conflicting results have been attributed to a number of key differences between the trials, wrote Dr. Anthony Miller of the University of Toronto in an accompanying editorial. The two trials used different PSA scores as a cutoff point and screened men at different intervals. The PLCO trial also had a substantial amount of "contamination"—more than half of men in the PLCO control arm underwent screening outside the trial. In addition, he pointed to evidence that there may have been different prostate cancer treatment in the screened versus control arms of the ERSPC study.
"We are left with an unsatisfactory situation, in which many practitioners will think there are insufficient data to recommend abandoning PSA screening for prostate cancer," Dr. Miller wrote. Because the PLCO results are more applicable to clinical practice in the United States, Dr. Miller said it would be "advisable" to follow the recent draft recommendations of the U.S. Preventive Services Task Force, which advise against PSA screening for prostate cancer among men considered to be at low risk of the disease.
Also in the Journals: Children and Adolescents with Acute Lymphoblastic Leukemia are Living Longer
An analysis of data from more than 21,000 children and adolescents treated for acute lymphoblastic leukemia (ALL) through clinical trials led by the Children's Oncology Group (COG) has found that 5-year survival rates rose from 83.7 percent between 1990 and 1994 to 90.4 percent between 2000 and 2005.
Survival improved among all children older than 1 regardless of age, sex, race or ethnicity, or ALL subtype. However, the relative risk of death varied among subgroups, with younger children faring better than adolescents, for example. Findings from the study, which includes the largest group of childhood ALL patients ever analyzed, were published online March 12 in the Journal of Clinical Oncology.
The study authors "believe that the major reason for improved survival [seen in this study] was decreased risk of relapse." Survival rates for children with ALL have risen dramatically since the 1960s due to improved treatment regimens with existing chemotherapy drugs, noted lead author Dr. Stephen Hunger of the University of Colorado. "Future improvements will depend, in large part, on developing new drugs to treat the hard-to-treat subsets of childhood leukemia," including infants less than a year old, Dr. Hunger said.
A Conversation With
A Conversation with Dr. Thomas Smith on the Growing Role of Palliative Care for Patients with Cancer
The American Society of Clinical Oncology (ASCO) recently released a Provisional Clinical Opinion (PCO) recommending that palliative care be integrated with cancer treatment early in the course of illness for any patient who has metastatic cancer or is greatly burdened by symptoms. The ASCO authors based their recommendation on the results of seven randomized trials that tested the addition of palliative care to traditional cancer care. One of the most recent of these studies showed that patients with advanced non-small cell lung cancer who received early palliative care not only had improved quality of life but lived longer than patients who received standard treatment alone. Dr. Thomas J. Smith, director of palliative care for the Johns Hopkins Sidney Kimmel Comprehensive Cancer Center and lead author of the PCO, talked with the NCI Cancer Bulletin about the growing role of palliative care in oncology practice.
Is palliative care integrated into traditional oncology training?
Palliative care is becoming more integrated into oncology training, but if you trained more than 10 years ago, you probably didn't learn much about it. Many oncologists don't really know how to integrate palliative care directly into their practice. I am still learning.
I think we oncologists typically have very good working relationships with our surgeons and our radiation therapy colleagues, but not often with palliative care providers. In fact, we should have the same sort of preferred provider relationship with hospice as we do with other specialties. By that, I mean we should choose one or two providers that we work with closely, get to know them really well, get to know what they can do and what they can't do, and get feedback from those hospice programs on how we could do better [on referrals].
What could be done now to expand access to palliative care for cancer patients?
One of the things is to get hospice involved much sooner in the care of our patients. We're asking oncologists to schedule a hospice information visit when they expect that a patient has 3 to 6 months left to live, where you send a hospice team to meet the patient and the family.
It's often easier for patients and families to talk about some of these things with someone other than their oncologist. Having that palliative care team to help make sure the patient understands his or her prognosis, making sure the patient understands what the treatment options are, what the treatment goals are—to really break things down in black and white—can be very helpful for both the oncologist and the patient.
About a third of patients go into hospice with less than a week to live, and everyone is scurrying around trying to get the patient comfortable when the outcome for that patient was predictable 3 to 6 months before. Most of us choose not to have discussions about things like hospice, do-not-resuscitate [orders], and advanced medical directives until there are no more chemotherapy options left. That allows us to avoid a hard conversation, but it doesn't serve as well to prepare the patients and families for what's coming.
Can palliative care help people with less-advanced cancers?
Yes, palliative care can help people who have curable cancers, too. When someone's getting bludgeoned by cancer treatment, it's really helpful to have someone else co-manage their symptoms. As an oncologist, I may not have the skills or the time—particularly the time, with a patient scheduled every 20 minutes—to help a patient with all of his or her physical and psychological symptoms. But if I have a good working relationship with a palliative care provider, a referral can be very helpful for me and the patient. Some particular examples are neuropathic pain and distress.
If the doctor recommends it, or if the advanced-practice nurse recommends it, it's a rare patient who's going to say, "Oh, I don't want to see the palliative care team." But again, it's up to us, as the treating oncologists, to refer patients. It is not as effective if we ask the social worker to handle it.
Is there work under way in the United States to standardize how palliative care is given?
There are already some very good standards. The Clinical Practice Guidelines for Quality Palliative Care, from the National Consensus Project for Quality Palliative Care, first came out in 2004. They're not proscriptive in that they don't tell you exactly what you can and can't do, but they do give you some very good ideas about what a good palliative care consultation should include.
A consultation should definitely include a symptom assessment, a screen for depression, a screen for spiritual distress, and referrals to a chaplain and psychologist, if indicated. The team itself should have some multidisciplinary components to it—not just a nurse, not just a doctor. I am concentrating on asking patients "What's important to you?" as a way into core matters.
The Joint Commission also offers an accreditation program that was just established this past year. So, the Joint Commission now approves palliative care centers, just as it approves stroke centers or heart-disease centers.
What are the most urgent research priorities for palliative care in oncology?
One is to test palliative care in diseases other than lung cancer, to do randomized trials of what we know works in lung cancer—which is a multidisciplinary palliative care intervention—in other cancers. Just like we tested stem-cell transplantation in myeloma, lymphoma, and breast cancer, let's test palliative care.
The other priority would be to try to figure out what are the main components in an effective palliative care intervention—what's necessary, what's sufficient [to see an effect]. Those results would have important implications for funding, because getting reimbursed [for palliative care] in today's environment can be really difficult.
How do caregivers benefit from palliative care?
I think that's one of the biggest areas of benefit. In several studies we looked at for the PCO, caregivers did extraordinarily better when someone other than the treating oncologist was helping to take care of the patients. Part of that has to do with knowing the prognosis, knowing the treatment goals, and knowing what's going to happen.
Patients and families want this information; the problem is that patients and families won't bring these questions up—they're waiting for us. So if we choose not to talk about these things, we're making a choice that seems easier in the moment—easier for us, easier emotionally for the families at the time—but it's a choice that will make care more difficult down the road.
And that's where having a palliative care team involved early can be so useful.
—Interviewed by Sharon Reynolds
Special Report
Surgeon General's Report Finds Youth Smoking Remains a Serious Concern
Smoking rates in the United States have dropped by half over the past four decades, due in large part to a diverse array of tobacco control efforts, including advertising campaigns and public smoking bans. This decline has been a rousing public health victory, marked by significant drops in lung cancer cases and death from the disease.
A new Surgeon General's report, however, clearly indicates that significant challenges remain. Preventing Tobacco Use among Youth and Young Adults highlights some disturbing trends, including a major slowdown in the falling rates of tobacco use among adolescents and young adults and an uptick in smokeless tobacco use among certain youth groups.
Much of the blame for the changing trends, the report states, lies at the feet of the tobacco industry and its heavy marketing of tobacco products using strategies that particularly appeal to adolescents and young adults.
During a March 8 briefing on the new report, Surgeon General Dr. Regina Benjamin stressed that the stakes are high. "This report challenges us to end the [tobacco] epidemic among young people," she stated.
Tobacco control efforts must focus on adolescents and young adults, Dr. Benjamin said. Overall, about 600,000 middle school students and 3 million high school students currently smoke. Ninety percent of smokers begin before the age of 18, she added, and one-third of 18- to 26-year-olds smoke.
"That's a higher rate than any other age group," Dr. Benjamin said. "So this is a serious public health issue."
The last Surgeon General's report on youth and tobacco was issued in 1994.
"Since then we've learned a lot about the science of nicotine addiction, the health consequences of tobacco use among youth, patterns of youth tobacco use, how addiction develops, and determinants of addiction," said Dr. Yvonne Hunt of NCI's Tobacco Control Research Branch.
For example, there is sufficient evidence to conclude that smoking reduces lung function and impairs lung growth in children and adolescents, the report stated, and that it can lead to abdominal aortic atherosclerosis—the thickening of the portion of the aorta that runs through the abdomen—increasing the risk of heart disease and aortic aneurysms in young adults.
The new report is also the first to comprehensively analyze tobacco use behaviors among young adults. "That's important because this age group hasn't been a major focus of prevention efforts in the past," Dr. Hunt continued. "And yet it's a group where we see a significant amount of tobacco initiation, as well as escalation to nicotine dependence."
The portrayal of smoking in movies and other popular culture is a substantial cause of youth tobacco use, the report found, and tobacco industry marketing plays a large role in encouraging young people to smoke.
Despite legal limitations on tobacco marketing to youth, the tobacco industry still spends $29 million a day to market tobacco products, much of it aimed at counteracting taxes on cigarettes. As young smokers are more price-sensitive than older smokers, the report found, this kind of marketing tactic has a larger impact on youth.
In a major racketeering case, for example, a federal court found in 2006 that the country's biggest cigarette companies had known for decades that recruiting new, teenage smokers was essential for their continued profitability, and for that reason, they designed their marketing campaigns to target young people and to entice them to become lifelong smokers.
The marketing works, particularly on adolescents, stressed Assistant Secretary of Health Dr. Howard Koh. And, the report showed, adolescents are more susceptible to the addictive effects of nicotine.
"It's not an accident" when a teenager starts smoking, Dr. Koh said during the briefing.
Packaging all of the findings into a Surgeon General's report is important, noted Dr. Jean Forster of the University of Minnesota, whose research focuses on health policy and adolescent smoking. "It really highlights the weight of the evidence about the factors that influence tobacco use," Dr. Forster said. "And it emphasizes that we have not solved the problem."
The report comes at a time when many U.S. states have slashed spending on tobacco control, said Matthew Myers, president of the Campaign for Tobacco-Free Kids.
"Recent studies show that these programs not only reduce smoking and save lives, but also save money by reducing tobacco-related health care costs," Myers said in a statement.
Future gains will require a mix of proven tools and more research, Dr. Hunt said. "We know that there are important policy measures that can have an impact when implemented as part of a broad, coordinated strategy," she said. "But we also need research that will help us better understand how to intervene, especially during those early stages, to prevent experimental use of tobacco from escalating to more regular use.
New Tools to Help Teens Quit Smoking
- QuitSTART is an interactive mobile quit guide for teens that delivers cessation and mood management tips and tracks cravings and progress toward quitting. The app is currently only available for the iPhone, but an Android version is being developed.
- Smokefree Teen, an NCI initiative launched last December. A key feature of Smokefree Teen is SmokefreeTXT, a free text-message service that provides encouragement, advice, and tips for teens trying to quit smoking.
Mapping the Evolution of Cancer Cells in Leukemia
Using whole-genome sequencing, researchers have uncovered new clues to the genetic alterations underlying acute myeloid leukemia (AML) that arises in patients who were previously diagnosed with a myelodysplastic syndrome. Myelodysplastic syndromes develop when the bone marrow stops producing enough healthy cells, and some cases progress to what is known as secondary AML.
To identify genetic mutations driving this type of AML, researchers at the Washington University School of Medicine in St. Louis sequenced the genomes of abnormal cells (obtained from bone marrow) and normal cells (obtained from skin biopsies) from seven patients whose myelodysplastic syndrome had progressed to AML. Each patient had provided samples when they were diagnosed with a myelodysplastic syndrome and later when they were diagnosed with secondary AML.
By comparing the alterations in each sample, the researchers could track the genetic evolution of the cancer cells over time. They could also identify the cluster of cells that initially caused each cancer to develop—known as the founding clone. Then, they observed new clusters of cells, or daughter clones, that emerged.
The findings, published online March 14 in the New England Journal of Medicine, suggest that the secondary AMLs were derived from bone marrow cells carrying mutations that were present during the myelodysplastic phase of disease.
The collection of proteins within a tumor may be just as diverse as the collection of altered genes. A recent clinical study of samples from patient tumors found "a surprising degree of heterogeneity in protein expression both across the different patient samples and even within the same tumor."
"The reality is that tumors within a single patient can have different genetic changes, and we have observed this heterogeneity at the protein level as well," said Dr. Cesar Castro of Massachusetts General Hospital, who co-led the study. His team profiled the cells using a technology developed to diagnose cancer rapidly.
To better understand the heterogeneity in cancer cells, Dr. Castro continued, researchers will need minimally invasive techniques that can collect serial specimens, as well as new ways to extract as much information as possible from these samples.
"These diseases are combinations of multiple clones, and the clones have a relationship," said Dr. Timothy Graubert, the study's senior author. "In every case, the daughter cells of the founding clone carried forward mutations from the cluster of cells that caused the cancer in the first place."
Implications for Treatment
The finding that suspicious mutations in secondary AMLs were always derived from clusters of cells in myelodysplastic syndromes suggests that targeting these early mutations may be the most effective way to prevent the progression of the mutant cells, the researchers predicted. Drugs that target mutations found only in later-evolving cancer cells may be effective only against those cells, they noted.
To develop the most promising targets, "researchers need to determine whether a particular mutation is part of the founding structure of the [cancer] or whether it occurred at a later time," Dr. Graubert explained.
The researchers identified 11 mutations in the patients' cancer cells that were later found in other patients with AML, which is an indication that they may play a role in the disease. Four of the mutations had not been implicated previously in either myelodysplastic syndromes or leukemia.
In addition to sequencing DNA, the researchers profiled changes in the numbers of copies of genes, as well as in patterns of gene expression. Each cancer cell had hundreds of mutations, but the researchers predict that only a small percentage of these may drive the disease.
The additional mutations, however, provided the statistical power the researchers needed to track the evolution of clones over time.
"The deep sequencing allowed us to confirm that a mutation was present, and it gave us a sense of how many cells in a given sample carry the mutation," Dr. Graubert said. "We could then describe the heterogeneity of the [cancers] and construct a picture of clonal evolution."
A Model of Cancer
The study provides evidence to support a model of cancer that has been hard to test experimentally, noted Dr. Lucy Godley of the University of Chicago Medical Center in an accompanying editorial.
The model describes cancer as a series of acquired mutations and epigenetic alterations that start with a single mutated cell and accumulate in a progressive manner. As the process unfolds, "subclones" of cells acquire new properties that give the cells advantages, such as the ability to resist chemotherapy or to metastasize.
This theory has been around for years, Dr. Godley said in an interview. "But new technologies allow you to ask questions that you couldn't ask before. That's what's so exciting about these kinds of genome studies."
Another recent sequencing study—this one led by Dr. Charles Swanton of the London Research Institute—described the genetic variability within different regions of the same kidney tumor. Instead of sequencing the entire genome, the researchers analyzed the protein-coding regions, or exomes.
"We know that cancer can be heterogeneous, and there's probably an evolutionary relationship between different parts of a tumor mass or different cancer cells in leukemia," said Dr. Elaine Mardis, co-director of the Genome Institute at Washington University and a co-author of the AML study.
The new findings on tumor heterogeneity are consistent with previous work in breast cancer, she noted. For instance, her group conducted an analysis of four DNA samples from the same patient whereas another group compared tumors collected from a patient 9 years apart. Similarly, her group recently reported that, in de novo AML, when patients relapse after receiving chemotherapy, the clone that emerges is derived from a clone that was present at initial diagnosis.
Future Possibilities
Sequencing the genomes of individual cancer cells could reveal additional layers of genetic complexity, as Dr. Graubert and his colleagues noted in their study. This technology is in its infancy, but a recent pilot study suggests how this could work.
—Dr. Lucy Godley
Researchers at BGI (formerly the Beijing Genomics Institute) sequenced the exomes of 25 cells donated by an Asian man with a form of kidney cancer. Among other findings, the researchers discovered that the man did not have alterations in a gene closely associated with that disease in Western populations.
This study, published in Cell, produced interesting findings, but single-cell sequencing is not ready for clinical studies, noted Dr. Michael Dean, an investigator in NCI's Center for Cancer Research and a co-author of the study.
He added: "It is clear that, for at least some [cancer] types, we will need to use multiple samples and multiple methods of genomic analysis to develop a complete picture of a cancer that can be used to guide therapies."
Dr. Mardis agreed. "These studies are all very exciting because we're now getting to the point of being able to approach [cancer] in different ways."
Featured Clinical Trial
Combining Systemic Therapies for Patients with Advanced Liver Cancer
Name of the Trial
Phase III Randomized Study of Sorafenib Tosylate with Versus without Doxorubicin Hydrochloride in Patients with Locally Advanced or Metastatic Hepatocellular Carcinoma (CALGB-80802). See the protocol summary.
Principal Investigator
Dr. Ghassan Abou-Alfa, Cancer and Leukemia Group B
Why This Trial Is Important
Primary liver cancer (hepatocellular carcinoma) is one of the leading causes of cancer death worldwide. Although it is still relatively uncommon in the United States, liver cancer incidence in this country nearly tripled between 1975 and 2008 and continues to rise. Much of the increase in the U.S. population can be traced to rising rates of infection with hepatitis C virus. Other risk factors include alcohol-related cirrhosis of the liver, which accounts for about one-third of U.S. liver cancers, as well as a condition called nonalcoholic steatohepatitis (NASH), which can develop among diabetic and morbidly obese people. As the incidence of diabetes and obesity increases, liver cancer related to NASH is likely to increase.
Localized liver cancer that can be surgically removed (resected) is potentially curable, but most patients are not diagnosed until the cancer has become advanced. Until recently, patients with advanced unresectable liver cancer were often treated with the drug doxorubicin, despite little evidence of a survival benefit. In 2007, however, a large randomized phase III trial found that patients with advanced liver cancer who were treated with the targeted drug sorafenib survived nearly 3 months longer than those treated with a placebo.
At the same time, Dr. Abou-Alfa and other researchers were conducting a randomized phase II trial to evaluate the addition of sorafenib to doxorubicin. The analysis of data from the trial showed that patients who received sorafenib plus doxorubicin experienced longer overall survival and progression-free survival than those who received doxorubicin plus a placebo. On the basis of these findings, together with preclinical data that suggest a possible synergistic effect between doxorubicin and sorafenib, researchers decided to compare the combination treatment with sorafenib alone.
In this phase III trial, patients with unresectable, locally advanced or metastatic primary liver cancer who have good liver function (Child-Pugh score A) will receive sorafenib and be randomly assigned to also receive either doxorubicin or no additional therapy. Doctors will compare overall survival between the groups, as well as progression-free survival and tumor responses.
"Doxorubicin was historically accepted based on the experience of individual doctors, but it was not a proven standard of care," said Dr. Abou-Alfa. "In this context, and before sorafenib became recognized as a standard of care, we carried out our phase II study comparing doxorubicin and sorafenib to doxorubicin alone. We noticed improved survival but we cannot say if that improvement was entirely due to sorafenib or if doxorubicin also contributed to the benefit. The current study should answer that question."
For More Information
See the lists of entry criteria and trial contact information or call the NCI's Cancer Information Service at 1-800-4-CANCER (1-800-422-6237). The toll-free call is confidential.
CDC Update
Federal Campaign Seeks to Shrink Smoking Rates Further
A series of "hard-hitting" ads designed to encourage adult smokers to quit began hitting airwaves, billboards, and print publications nationwide yesterday, in the first-ever Federal antismoking campaign. Funded by the Centers for Disease Control and Prevention (CDC), the ads feature real people who have suffered serious, often disfiguring health problems caused by smoking, as well as former smokers offering guidance on how to quit.
The campaign, called "Tips from Former Smokers," will run for 3 months and will include ads in Spanish and English. The campaign "tells the real story of how tobacco can change your life," said Health and Human Services Secretary Kathleen Sebelius during a briefing to announce the campaign's launch.
Although great gains have been made in reducing smoking rates, progress has stalled during the last decade. Approximately 20 percent of Americans still smoke.
The campaign builds on an effort launched by President Barack Obama's administration to reverse that trend, Sebelius explained, including provisions in the Affordable Care Act that require coverage of smoking cessation services and the Family Smoking Prevention and Tobacco Control Act, which greatly expanded the Food and Drug Administration's regulatory authority over tobacco products.
The administration's efforts are intended "to help the 70 percent of smokers who want to quit to make that leap," Sebelius said. The ads direct people to 1-800-QUIT-NOW and www.smokefree.gov.
One of the ads features Terrie Hall from North Carolina, who started smoking when she was 17 and eventually smoked two packs a day. Diagnosed with laryngeal cancer at the age of 40, Hall had to have her voice box removed. In the ad, Hall demonstrates how she gets ready for her day: putting in false teeth, placing a blond wig onto her mostly bald head, and inserting a filter into her stoma, a surgically created opening in her windpipe.
In 2008, NCI analyzed research literature about the impact of media on tobacco use. Results from this detailed analysis found that ads such as those being used in CDC's current campaign effectively reduce smoking.
"The ads only work if they're done right," CDC Director Dr. Thomas Frieden said during the briefing. "And the evidence is clear that hard-hitting ads work."
The agency predicts that the campaign will help 50,000 smokers quit. Its cost, $54 million, is equivalent to what the tobacco industry spends in 2 days on marketing its products, Dr. Frieden said.
Many states have been criticized for cutting back on their tobacco control programs, and most states currently spend far less than the CDC recommends. But the new campaign is not meant to replace states' tobacco control efforts, only augment them, Dr. Frieden cautioned.
"I understand that states are under considerable pressure economically. But tobacco control is a good buy," he continued, noting that it can significantly reduce Medicaid costs and other health care spending and improve productivity.
Some people have argued that the current 20 percent smoking rate is "some sort of irreducible minimum," he said. But a number of states that have consistently invested in tobacco control have reduced smoking rates to well below 20 percent, he stressed. "More progress is possible."
NCI and CICAMS Sign Statement of Intent
Dr. Jie He, president of the Cancer Institute and Hospital of the Chinese Academy of Medical Sciences (CICAMS), and NCI Director Dr. Harold Varmus signed a statement of intent to share an interest in fostering collaborative biomedical research in oncology and a common goal in educating and training the next generation of cancer research scientists and clinicians. The signing took place March 14 during the Setting Priorities for Global Cancer Research meeting, hosted by NCI's Center for Global Health.
NCI and CICAMS aim to improve the discovery and development of new anticancer agents and prevention strategies to enhance the design, implementation, and analysis of cancer treatment and prevention trials, basic science research, and epidemiologic studies.
NCI and CICAMS intend to collaborate on the following activities:
- Basic and translational research
- Preclinical research and clinical trials and associated translational research
- Cancer prevention and early detection trials and epidemiologic studies
- Joint meetings, conferences, workshops, and informational exchanges
NCI-supported researchers and CICAMS researchers have collaborated on scientific projects for more than 30 years. CICAMS was recently designated China's National Cancer Center and will have an expanded role in China's cancer prevention and control efforts.
NCI Advisory Committee on Clinical Trials Holds First Meeting of 2012
The Clinical Trials and Translational Research Advisory Committee (CTAC) held its first meeting of 2012 on March 7 on the NIH main campus in Bethesda, MD.
The meeting highlighted NCI-supported early-phase prevention and treatment clinical trials programs, including the Division of Cancer Prevention's Consortia for Early Phase Prevention Trials, and the Early Experimental Therapeutics Program and the Cancer Diagnosis Program's biomarker resources, both in the Division of Cancer Treatment and Diagnosis.
The agenda, presentations, and a link to the archived videocast are available online. The next two CTAC meetings are scheduled for July 11 and November 30, 2012.
NCI at American Association of Cancer Research Annual Meeting
NCI staff will be participating at the American Association for Cancer Research's 103rd Annual Meeting from March 31–April 4 in Chicago, IL. Learn about sessions with NCI staff and activities at the NCI exhibit booth online.
Look for highlights from the meeting in the April 3 issue of the NCI Cancer Bulletin.
Dr. John Potter to Deliver First Schatzkin Lecture in Nutritional Epidemiology
The inaugural Arthur Schatzkin Distinguished Lecture in Nutritional Epidemiology will be held at 3:00 p.m. on April 16 in Lipsett Amphitheater on the NIH main campus in Bethesda, MD. NCI established this annual lecture to honor the memory of Dr. Arthur Schatzkin, a visionary scientist, mentor, and leader in the field of nutrition and cancer.
Dr. Schatzkin joined NCI in 1984 and served as the chief of the Nutritional Epidemiology Branch from 1995 to 2011. He was committed to understanding the role of nutrition in cancer etiology and prevention and was instrumental in addressing major methodological issues of research in nutritional epidemiology. Dr. Schatzkin passed away in January 2011.
This year's lecturer is Dr. John Potter, member and senior advisor of the Division of Public Health Sciences at Fred Hutchinson Cancer Research Center and professor of epidemiology at the University of Washington. Dr. Potter's research focuses on the role of diet and physical activity in the development of cancer, with a particular emphasis on the epidemiology, biology, early detection, and prevention of colon cancer. The title of his talk is "Nutrition, Environment, Development, and Cancer: Casting a Wider Net."
New Complementary and Alternative Medicine Report and Information Posted Online
In fiscal year 2010, NCI funded more than 400 projects related to complementary and alternative medicine (CAM), and the American Recovery and Reinvestment Act supported 27 other CAM grants, according to NCI's Annual Report on Complementary and Alternative Medicine.
Projects highlighted in the report include studies on exercise and cancer prevention, curcumin's role in preventing the spread of prostate cancer, and the effect of altering cellular fats on cancer risk. Researchers are also examining whether various foods can prevent or fight cancer. For instance, blackberries are being studied to determine whether they interfere with the growth of tumors in the oral cavity, esophagus, and colon.
In addition, NCI's Physician Data Query (PDQ®) webpage on Prostate Cancer, Nutrition, and Dietary Supplements has been updated with new information on modified citrus pectin, soy, and pomegranates.


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Take a scenic cruise on your vacation. Our Bellingham, Washington boat tours will allow you to see the sights from the view on the water. Relax and enjoy the scenery on our Bellingham, Washington scenic cruises. Browse our Bellingham, Washington scenic cruises and boat tours and plan your vacation today!
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Household items you're paying too much for
Published On: Jan 19 2012 10:01:17 AM PST Updated On: Dec 26 2012 11:00:00 PM PST
Find out which household items you could be saving money on.
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Before Liz Lemon, before "Weekend Update", before "Sarah Palin", Tina Fey was just a young girl with a dream: a recurring stress dream that she was being chased through a local airport by her middle-school gym teacher. She also had a dream that one day she would be a comedian on TV.
She has seen both of those dreams come true.
At last, Tina Fey's story can be told. From her youthful days as a vicious nerd to her tour of duty on Saturday Night Live; from her passionately halfhearted pursuit of physical beauty to her life as a mother eating things off the floor; from her one-sided college romance to her nearly fatal honeymoon - from the beginning of this paragraph to this final sentence.
Tina Fey reveals all, and proves what we've all suspected: you're no one until someone calls you bossy.
Includes special, never-before-solicited opinions on breastfeeding, princesses, Photoshop, the electoral process, and Italian rum cake!
PLEASE NOTE: When you purchase this title, the accompanying reference material will be available in your My Library section along with the audio.
©2011 Tina Fey (P)2011 Hachette Audio
"I hope that's not really the cover. That's really going to hurt sales." (Don Fey, Father of Tina Fey)
"Do not print this glowing recommendation of Tina Fey's book until I've been dead a hundred years." (Mark Twain)
"Hilarious and insightful. Laugh-out-loud funny - oh no, a full moon. No! Arrgh! Get away from me! Save yourself!" (A Guy Turning into a Werewolf)
"Tina Fey broke my new SUV"
With 3124 on my new SUV's odometer, I was laughing so hard listening to Tina that I clipped a cement highway divider driving to work.
That's not the funny part.
I kept on laughing.. Tina Fey is like comedic Oxytocin.
Buy this book. Keep both hands on the wheel.
I am enjoying this book just as much as 30 Rock. It's brilliant and not particularly sappy, and Tina Fey does the reading of the book credit as well (some authors are not such great readers, but this is certainly not the case!).
To those who can't seem to find the PDF mentioned occasionally in the audio book: you can download it from the "library" section right under to the link for the book. It's not essential, but it's nice.
"Great book--great listen!"
She's just amazing and I thoroughly enjoyed this book! She takes us from her life as a kid in Philly to writing/starring/producing 30 Rock with the sharp wit and self deprecation that we've come to know her for. It's especially interesting to listen to what's going on behind the scenes at SNL or 30 Rock and how certain decisions were made (Sarah Palin, casting 30 Rock, etc...)
And of course, her asides are hilarious.
Loved it!
"Truely enjoyable."
Absolutely awesome audiobook. It's almost always better when the author narrates their own book and in this case Tina's narrative definitely makes Bossypants one of the most enjoyable books I've listened to/read so far.
Her comments and jokes are witty and finely crafted, yet they're presented as an effortless, logical, and mostly hilarious conclusion to the situation she's in. It's everything you hoped it would be.
(Just FYI: the PDF she refers to in the audiobook can be downloaded from "my library" once you've bought the audiobook. )
"A reader lives a thousand lives before he dies. The man who never reads lives only one." - Jojen Reed. #ADanceWithDragons
"Witty and Funny"
If you like Tina Fey, you will like this title The book is simply entertaining to say the least, funny, witty, insightful and generally a feel-good book. Its one of those books that you will have you cracking up from the get go. The book chronicles her life and her rise to being 'Tina Fey' we all like to laugh with and at. Childhood, teenage years, a view of her parents, SNL, Sarah Palin skit and the 30 Rock. Utterly funny through and through and you will not find a section that you cannot find some laughs in. A great listen!
"Thoroughly entertaining!"
I loved this book so much that I didn't want to turn it off. I was listening to it while hiking at the mountain and I got some amused looks when passers-by saw me laughing out loud. It's funny, interesting, insightful and honest. My only disappointment is that it ended.
Say something about yourself!
"I want to go to there"
I'm of the mindset that if you write a memoir you need to narrate the audiobook yourself (it's the one time I'll give bad narration a pass.) "Bossypants" is all the better because of Tina Fey's narration. She's incredibly engaging and her dry, self-deprecating humor will keep you laughing the whole way through. I'm a big fan of "SNL" and "30 Rock" so it was really interesting to get a behind-the-scenes look at the shows. And her opinion of Red Lobster Cheddar Bay biscuits is spot on!
Don't listen to this book while driving. Telling the cop after an accident that an audiobook made you shoot coffee out your nose is not a good enough excuse apparently. A side note for people looking for the PDF, go to your library at audible look under the title (Bossypants) and right under that are the letters PDF. click on that and magically, the PDF shows up on your computer. taa-daa! Funny funny book
I am a clay sculptor and an art instructor at a community college. I mostly listen to audiobooks while I work in my home studio.
I enjoyed the start of the book but it won me over with the mom stuff. yeah.
I like Tina Fey generally, but I'm not a big fan of 30 Rock so I wasn't sure about the book. (for the record, I think the story lines are ridiculous, I think Alec Balwin is slightly annoying and I many of the 30 Rock jokes make me feel slightly uncomfortable.)
I didn't think this book had any of the problems that 30 Rock has. Tina Fey seemed a bit neurotic but mostly just funny. I like her sarcastic take on most things (exception being: She seems pretty amazed by Alec Baldwin in a way I don't get).
I was listening to the audiobook (earphones), in part, while my daughter napped. I laughed out loud several times and was actually worried that I'd wake her.
Like I said, I particularly laughed at some of the times she talked about being a working mom and the pressures of being a mom (working or otherwise) in society today. This stuff always gets me, because I found the first 6 months of motherhood to be really hard and I like hearing from otherwise successful people who also had a hard time. Especially if they make it seem ridiculous that other people made you feel bad then. yeah.
anyway, its pretty short. You should probably read it. the book generally had some pretty right-on moments that I haven't heard before. It wasn't heavily SNL, 30 Rock or even feminist (I wouldn't have minded the former or the latter). I kept feeling that she concisely poked at a bit of truth over and over again, in a way that was light, funny and real.
I enjoy watching Tina Fey on 30 Rock and Saturday Night Live so I thought I would give her audiobook a try. It was funny and really lets you see into her life a little. Tina narrates it herself so it feels like she is telling you personally her story. I wish it was longer than 5 hours but that seems about typical for most bios. Warning there is a lot of language so it's not one to put on in the car with the kids. Oh, make sure you download the PDF it goes with the book, I did not realize there was a PDF until she kept saying check the PDF at first I thought it was a joke but no there really is a PDF with this book. After you buy the book go into your library and find Bossypants. Under the title there is PDF click on it and save it. I wish all bios you get on audiobook would come with the pictures that are with the print book.
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Weekend DiscussionAssuming that (The) Sweet is trustworthy, it seems the man in the back said everyone attack and it turned into a ballroom blitz. Furthermore, the girl in the corner said "Boy, I wanna warn you it'll turn into a ballroom blitz." Ballroom blitz? Ballroom blitz!
With that, the song should now be stuck in your head. Have a nice weekend!
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FIFA 15 Review
Peter tries to get up close with some balls, but FIFA 15 is making things harder than ever for fans of the tackle.
Peter tries to get up close with some balls, but FIFA 15 is making things harder than ever for fans of the tackle.
Latest PC Game News
League of Legends Champion Spotlight reveals Azir
Riot have put their spotlight on a forthcoming League of Legends Champion: Azir, Emperor of the Sands.
Firefall update 1.1, Elemental Destruction, out today
Update 1.1 for MMO shooter Firefall – titled Elemental Destruction – is apparently out today.
On the eve of release for Rome 2's Emperor Edition, Peter returns to the game to see how it fares after a fifteenth major patch.
SteamWorld Heist revealed by SteamWorld Dig devs
I'm taking a bit of a punt on this since platforms are "still to be announced," but as SteamWorld Dig made it to the PC it seems a reasonable bet that the follow-up will too.
Cities: Skylines gets two new screenshots
Paradox finally release some new Cities: Skylines screens to impress city builder fans.
Is the PC GTA 5 delay justified? Will you buy it? What's your opinion?
Rockstar pushed back the release of GTA 5 on the PC to 2015 but is it justified?
Sleeping Dogs: Triad Wars still exists, details being "tightly controlled"
The silence around Sleeping Dogs: Triad Wars is due to information about the game being "tightly controlled" at present, according to a United Front Games community spokesperson.
Far Cry 4 trailer supplies some dubious elephant facts
As well as being able to use tools and learn human languages, elephants can headbutt a jeep further than any other mammal.
Divinity: Original Sin gets two new DLC companions, free
The two bonus companions for Divinity: Original Sin have now been released, and are free to everyone.
Gamers think the Sims 4 is "OK" – The results are in
The Sims 4 has been out for over a week and we asked for your opinions on the game.
Australians can now play Left 4 Dead 2 uncensored
It may be old but at least the Aussie can now enjoy it in its full glory.
Borderlands: The Pre-Sequel video looks at creating the characters
Time to go behind the scenes once again with the development team.
Divinity: Original Sin patched ahead of companion DLC
Divinity: Original Sin is getting some new companions as free DLC later today, but the game has been patched now to fix some lingering issues.
Star Citizen Arena Commander patched to fix queue issues
Cloud Imperium dive into the Star Citizen Arena Commander patch fixing over the weekend to sort out some problems.
Microsoft's $2.5 billion Mojang purchase expected on Monday
Sorry Minecraft fans, the unstoppable hand of Microsoft's capital seems like it's slowly closing around the neck of your game.
Paul takes to the tracks in his 300i to test out the new race mode. He also dies a lot.
Steam celebrates 11 years and everyone loves it now
Steam celebrates another year of serving PC gamers everywhere. When Steam launched back in in 2003 it wasn't exactly greeted with enthusiasm.
Star Citizen Arena Commander v0.9 released
Get your racing helmet on, the patch is finally here with a load of updates.
Game Expo Scotland cancelled due to lack of publisher support
Some devastating news for gamers north of the border looking forward to this event.
Star Citizen's M50 trailer hits the top gear of parody
A new trailer for the Origin M50 ship reveals the horrifying truth; that a version of Jeremy Clarkson still exists in the future.
Divinity: Original Sin – post-release update from Larian's Swen Vincke
Larian's Swen Vincke has written another of his semi-regular blog posts about the industry, expanding on some thoughts about the release of Divinity: Original Sin.
FIFA 15 TV ad wants you to "Feel the Game" and the balls
It's getting close to release and FIFA 15's balls are getting more exposure via the moving picture box in your living room.
Naruto Shippuden: Ultimate Ninja Storm Revolution gets launch trailer
Naruto Shippuden: Ultimate Ninja Storm Revolution now has a launch trailer.
Star Citizen smashes through the $53 million funding goal
Cloud Imperium are obviously dropping the ball with Star Citizen because this goal took almost two weeks to reach.
Elite: Dangerous release and pre-order prices revealed – Multiple ship ownership confirmed
Frontier nail down the pricing for their space epic Elite: Dangerous and reveal pre-order bonuses.
Magicka 2 gets a karaoke trailer
The latest trailer for Magicka 2 is, uh… a karaoke trailer.


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GREY'S ANATOMY - "This Is Why We Fight" - As word of Seattle Grace's financial trouble spreads, Catherine encourages Jackson to move to Boston, and the interns fear they might lose their jobs. Meanwhile, the doctors meet with a potential investor in a last-ditch effort to save the hospital, and Alex impresses Jo while caring for a patient.
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Moderators: Jenise, David M. Bueker, Robin Garr
Barb Freda wrote:The case of mangos.
The flat of fresh figs.
Christy M. wrote:They pay their employees a great wage, provide medical and other benefits and the CEO Jim Sinegal refuses to let corporate greed undermine treating employees well. Costco shows that you can make an excellent profit and provide a working wage to employees.
John Tomasso wrote:I have to say though, that I don't find it as compelling a place to shop as many of you do. Maybe because I've always had access to restaurant quality and pack sizes, I find it less of a novelty than some. And I can't stand the long lines.
Carrie L. wrote:We think Costco's meat is excellent, everything
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As a general rule, your baggage will automatically be forwarded to the final destination regardless of whether you are travelling domestically or internationally. However, your baggage should be labelled. If in doubt, you can always ask.
Baggage carts are available in Kastrup Airport's transfer area. They allow you to transport your baggage easily and comfortably.
If you are arriving at Copenhagen Airport from a country outside of the EU and are travelling onward, you must pass through security control. Please be aware that the same restrictions on liquids apply for the second departure from the airport.
Passengers who are in transit at the airport cannot bring bottles of liquor or perfume over 100 ml/3.38 oz. The total number of containers per passager must be able to fit in a plastic bag with a volume of 1 liter unless if the goods are sealed in the store and not opened before arrival at the destination.
Scandinavian Airlines © 2014


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Nobel Prizes
Associated Press
News about Nobel Prizes, including commentary and archival articles published in The New York Times.
Chronology of Coverage
Sep. 16, 2014
Dennis Overbye Out There column profiles Dr Peter Higgs, 85-year-old physicist who first theorized existence of new particle that would explain how other particles get mass in 1964; Higgs, who won 2013 Nobel Prize in Physics for discovery, is in many ways as elusive as particle he helped uncover. MORE
Aug. 10, 2014
Gray Matter column by graduate student Michael J Barany describes history of the Fields Medal, top prize in field awarded by International Congress of Mathematicians; contends that true story of award, which was started after mathematics was omitted from Nobel Prize, helps illuminate often neglected intersection of mathematics and politics. MORE
Nov. 21, 2013
Frederick Sanger, British biochemist whose discoveries about the chemistry of life led to the decoding of the human genome and to the development of new drugs like human growth hormone, dies at age 95; Sanger's work earned him two Nobel Prizes. MORE
Nov. 17, 2013
Jeff Sommer Strategies column notes that Lars Peter Hansen, economist who shared the 2013 Nobel Prize in economic science with Eugene Fama and Robert Shiller, will not let himself be drawn into the debate among them on the financial markets' behavior; his recent work has dealt with linkages between markets and the economy. MORE
Oct. 27, 2013
Jeff Sommer interview with Eugene F Fama, economist and co-winner of 2013 Nobel Memorial Prize in Economic Science; he is known as the father of the efficient-markets theory. MORE
Oct. 27, 2013
Robert J Shiller Economic View; co-winner of 2013 Nobel Memorial Prize in Economic Science explains areas of disagreement with his fellow laureates Eugene F Fama and Lars Peter Hansen; notes this is not the first time co-recipients have had differing views. MORE
Oct. 21, 2013
Raj Chetty Op-Ed article disputes criticisms lobbed at field of economics by some skeptics after Nobel prizes were awarded to three economists with opposing ideas; refutes idea that disagreements about answers to specific questions provides evidence that economics is fake science. MORE
Oct. 20, 2013
Robert J Shiller, Yale professor and co-winner of Nobel Memorial Prize in Economic Science, talks in interview about forces that made him a questioning, data-driven economist. MORE
Oct. 19, 2013
Alice Munro, winner of the Nobel Prize in Literature, will be unable to travel to Stockholm to accept her award because of health reasons. MORE
Oct. 15, 2013
Professors Eugene F Fama, Lars Peter Hansen and Robert J Shiller share the Nobel Memorial Prize in Economic Science; their work shows that stock and bond prices move unpredictably in short term but tend to follow established rules in the long term; Fama believes in rational market, while Shiller does not. MORE
Oct. 15, 2013
The Week column; Nobel Prize in Physics is awarded to Peter W Higgs of the University of Edinburgh in Scotland and Francois Englert of the Universite Libre de Bruxelles in Belgium for theory, first put forth in 1964, that there is a particle that confers mass to other particles, known as HIggs boson; other notable developments in science and medicine highlighted. MORE
Oct. 12, 2013
Norwegian Nobel Committee awards 2013 Peace Prize to the Organization for the Prohibition of Chemical Weapons, agency that is working to destroy Syria's stockpile. MORE
Oct. 12, 2013
Op-Ed article by Jochen Bittner, political editor of German newspaper Die Zeit, rebuts critics who say the Nobel Peace Prize has become overly politicized in recent years; contends that panel has done excellent job overall, and that replacing Norwegian jurists with international group would only further politicize the prize. MORE
Oct. 11, 2013
Michiko Kakutani An Appraisal essay acknowledges achievements of Alice Munro, winner of the 2013 Nobel Prize in Literature; says she has helped redefine the contours of the modern short story, with quietly radiant stories that have swoop and density of big, intimate novels, possessing emotional amplitude and psychological density. MORE
Oct. 11, 2013
Renowned Canadian short-story writer Alice Munro wins 2013 Nobel Prize in Literature; she is honored for visceral work that explores tangled relationships between men and women, small-town existence and the fallibility of memory. MORE
Oct. 11, 2013
Editorial praises the writing of author Alice Munro, who was awarded the Nobel Prize in Literature; holds what is most admirable in her work is the pace of her storytelling. MORE
Oct. 10, 2013
Nobel Prize in Chemistry is awarded to Martin Karplus, Michael Levitt and Arieh Warshel, recognized for computer simulations that enable closer study of complex reactions like photosynthesis and design of new drugs; winning researchers are notable for work that does not involve test tubes or lab coats, but instead, explores world of molecules virtually, with computers. MORE
Oct. 9, 2013
Francois Englert of Belgium and Peter W Higgs of Britain, theoretical physicists who suggested an invisible ocean of energy is responsible for the mass and diversity of the universe, win Nobel Prize in Physics; their 1964 theory sent physicists on a generation-long search for a particle that confers mass on other particles, also known as Higgs boson, culminating in its discovery in 2012. MORE
Oct. 8, 2013
Americans James E Rothman, Randy W Schekman, and Thomas C Sudhof win the Nobel Prize in Physiology or Medicine for discovering machinery that regulates how cells transport major molecules in a cargo system that delivers them to the correct destination at the right time. MORE
Oct. 8, 2013
Many observers expect that University of Edinburgh professor Dr Peter Higgs, 84, whose name is attached to landmark discovery the Higgs boson, will be awarded a Nobel Prize in Physics, but there are other strong candidates. MORE
Oct. 2, 2013
Russian advocacy group International Academy of Spiritual Unity and Cooperation of Peoples of the World nominates Pres Vladimir V Putin for Nobel Peace Prize; group says Putin is more deserving of prize than Pres Barack Obama, who received it in 2009 but has continued to lead American military operations that have killed civilians abroad. MORE
Sep. 29, 2013
Op-Ed article by writer Bill Wyman argues that Bob Dylan should win the Nobel Prize in Literature. MORE
Sep. 25, 2013
Dr David Hubel, who with his collaborator Dr Torsten Wiesel won 1981 Nobel Prize for explaining how the brain assembles information from the eye's retina to produce detailed visual images of the world, dies at age 87. MORE
Apr. 10, 2013
More than 50 Nobel laureates sign open letter urging Congress to spare federal science establishment from looming budget cuts, arguing that further reductions would endanger innovation that is essential to economy. MORE
Dec. 11, 2012
European Union accepts Nobel Peace Prize with calls for further integration; prize ceremony is attended by 20 European leaders as well as Norway's royal family. MORE
Nov. 15, 2012
European Union will donate money from its Nobel Peace Prize to create projects for children in war zones. MORE
Oct. 18, 2012
Op-Ed article by Larry Siems, head of PEN American Center's Freedom to Write program, and Jeffrey Yang, translator of Liu Xiaobo book of poetry, compares reactions of Nobel laureates Mo Yan and Liu to news that they had won prize in literature; observes that two writers illustrate two different paths literature can take under Chinese regime. MORE
Oct. 16, 2012
Americans Alvin E Roth and Lloyd S Shapley are awarded Nobel Memorial Prize in Economic Science for their work on market design and matching theory, which relate to how people and companies find and select one another. MORE
Oct. 14, 2012
Op-Ed article by physics and astronomy Prof Adam Frank explores and explains field of quantum information, which was brought to public attention by Nobel Prize in Physics being awarded in that field; contends that advances in quantum information will most probably affect human society more than advances in related field of quantum physics. MORE
Oct. 13, 2012
Norwegian Nobel Committee makes unconventional choice in awarding the 2012 peace prize to the European Union, celebrating its six decades of postwar integration even as financial crisis and political infighting threaten to tear it apart. MORE
Oct. 13, 2012
Editorial contends Norwegian Nobel Committee's decision to award its peace prize to the European Union is yet another example of the organization using its prestige to send a political message. MORE
Oct. 12, 2012
China erupts in something close to national celebration for writer Mo Yan, who won the Nobel Prize for literature, just two years after the government condemned Nobel Peace Prize for dissident Liu Xiaobo; award will probably act as huge boost to China's national psyche, which has suffered from sense that its cultural accomplishments are overshadowed by its economic prowess. MORE
Oct. 12, 2012
Richard Bernstein An Appraisal column of work of Mo Yan, winner of Nobel Prize for Literature, much of which focuses on daily lives of ordinary people in China. MORE
Oct. 12, 2012
Excerpts from work of Mo Yan, winner of 2012 Nobel Prize in Literature. MORE
Oct. 11, 2012
American scientists Dr Robert J Lefkowitz of Duke and Dr Brian K Kobilka of Stanford are awarded the Nobel Prize in Chemistry for their work on deciphering the communication system that the human body uses to sense the outside world and send messages to cells; understanding could be used to refine drug design, producing more selective and effective medications. MORE
Oct. 10, 2012
Quantum physicists Serge Haroche and David J Wineland win the Nobel Prize in Physics for their work examining the relations between light and matter. MORE
Oct. 9, 2012
John B Gurdon and Shinya Yamanaka are awarded Nobel Prize in Physiology or Medicine for their foundational work in regenerative medicine; their discoveries, which occurred fifty years apart, concern manipulation of living cells and lie at the heart of techniques for cloning animals and generating stem cells. MORE
Aug. 7, 2012
Bill Breisky essay recounts his memories of his grandfather, Victor Francis Hess, who discovered the existence of cosmic rays a century ago, winning the 1936 Nobel Prize in Physics for his efforts. MORE
Jun. 17, 2012
Burmese opposition leader Daw Aung San Suu Kyi speaks of the hope her award kindled in 1991, when she was under house arrest in Myanmar, as she finally accepts her Nobel Peace Prize in Oslo. MORE
Jun. 16, 2012
Burmese democracy leader Daw Aung San Suu Kyi arrives in Norway to finally deliver the Nobel lecture for the peace price she won in 1991. MORE
Jun. 15, 2012
Myanmar's pro-democracy leader Daw Aung San Suu Kyi begins her 17-day tour of Europe, which will include a stop in Norway, where she will collect the Nobel Peace Prize awarded to her in 1991. MORE
Jun. 12, 2012
Lab notebooks uncovered at Rutgers University may help settle a 70-year argument over the Nobel-winning discovery of streptomycin, the first antibiotic to cure tuberculosis; streptomycin was first isolated in 1943 by graduate student Albert Schatz, who later fought a prolonged legal battle with his supervising professor, Selman A Waksman, who received the Nobel prize for the discovery. MORE
Apr. 24, 2012
Former Soviet Union Pres Mikhail S Gorbachev gives a talk at a public high school in Chicago; he is there for a gathering of Nobel Peace Prize winners, some of whom are also addressing local students. MORE
Dec. 20, 2011
Convoluted will left by Alfred Nobel left much room for interpretation and confusion as to how to award the prizes that bear his name; Nobel committee mandated that award be given only to living people starting in 1970, rule that has been violated four times. MORE
Dec. 11, 2011
Nobel Peace Prize is awarded to Liberia's President Ellen Johnson Sirleaf, Liberian activist Leymah Gbowee and Yemeni journalist Tawakkol Karman for their campaigns to advance women's rights and safety. MORE
Dec. 4, 2011
Thomas J Sargent of New York University and Christopher A Sims of Princeton, winners of the 2011 Nobel prize in economics, are quiet, celebrity-shy professors; conservatives claim them as their own, but both are longtime Democrats who maintain that government can, and should, play a role in economic affairs; their research goes beyond old labels to level of empirical analysis that few outside profession can readily grasp. MORE
Oct. 16, 2011
Jeff Sommer Strategies column on Nobel prize-winning economists Thomas J Sargent and Christopher A Sims, who are uncomfortable with limelight and pidgeonholing they have been subject to since winning the award. MORE
Oct. 12, 2011
Editorial maintains that in awarding the 2011 Nobel in economic sciences to Christopher Sims and Thomas Sargent, whose research examines the relationship between government policy and economic outcomes, the prize committee delivered a challenge to politicians who are driven more by ideology than by consideration of the real-world consequences of their actions. MORE
Oct. 11, 2011
Americans Thomas J. Sargent and Christopher A. Sims win the Nobel price in economic science for their empirical research on cause and effect of government policies on the broader economy. MORE
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Obama Can Still Earn His Nobel
The leader who didn't have a strategy for dealing with Islamic State nihilists a few weeks ago just dropped an idea bomb on the rest of the world.
September 26, 2014, Friday
A Pioneer as Elusive as His Particle
The Nobel laureate Peter Higgs, 85, whose public appearances have been as rare and fleeting as the tracks of the Higgs boson, discussed his life's work in an interview at an Edinburgh cafe.
September 16, 2014, Tuesday
MORE ON NOBEL PRIZES AND: Higgs, Peter Ware , Higgs Boson , Physics , Nobel Prizes
How Math Got Its 'Nobel'
The true story behind the field's most prestigious award.
August 10, 2014, Sunday
MORE ON NOBEL PRIZES AND: Mathematics , Nobel Prizes , International Congress of Mathematicians , Awards, Decorations and Honors
Remembering Nadine Gordimer, a Lioness of Literary Activism
The writer leaves behind profoundly affecting artistic and political legacies — in both her native South Africa and beyond.
July 15, 2014, Tuesday
MORE ON NOBEL PRIZES AND: Gordimer, Nadine , Africa , South Africa , Israel , Nobel Prizes , Books and Literature , Palestinians , Apartheid (Policy)
Nobel Laureate's Release from Prison May Hinge on His 'Regret'
Liu Xiaobo, who was awarded the Nobel Peace Prize in 2011 and is serving an 11-year prison term for subversion, is the world's only jailed Nobel laureate. On June 8, under Chinese law, he become eligible for parole.
May 28, 2014, Wednesday
MORE ON NOBEL PRIZES AND: Aung San Suu Kyi , Liu Xia , Liu Xiaobo , Link, Perry , Liu Hui , Tiananmen Square (Beijing) , Myanmar , China , Beijing (China) , Independent Chinese PEN Center , Political Prisoners , Nobel Prizes , Human Rights and Human Rights Violations
Gerald M. Edelman, Nobel Laureate and 'Neural Darwinist,' Dies at 84
After receiving the 1972 Nobel for a breakthrough in immunology, Dr. Edelman studied "how the brain gives rise to the mind."
May 23, 2014, Friday
MORE ON NOBEL PRIZES AND: Immune System , Brain , Edelman, Gerald M , Nobel Prizes , Deaths (Obituaries)
Norway Returns a Rare Silent Film to China
A print of "The Cave of the Silken Web," released in 1927, is believed to be the only existing copy of the film, which was directed by Dan Duyu and is based on an episode from the Chinese classic novel "Journey to the West."
April 15, 2014, Tuesday
MORE ON NOBEL PRIZES AND: Liu Xiaobo , Norway , China , National Library of Norway , China Film Archive , Nobel Prizes , Movies
A Pocket Guide to the 2014 Jaipur Literature Festival
From Friday through Tuesday, celebrated writers from India and abroad will talk about not just their books but also about the two World Wars, Afghanistan after the withdrawal of American troops, Himalayan languages and the making of modern China.
January 15, 2014, Wednesday
MORE ON NOBEL PRIZES AND: Lahiri, Jhumpa , Sen, Amartya , Rajasthan (India) , Jaipur (India) , India , Indian-Americans , Books and Literature , Writing and Writers , Women's Rights , Nobel Prizes , News and News Media , United States Economy , Pulitzer Prizes , Book Trade and Publishing
John W. Cornforth, 96, Nobel-Winning Chemist, Dies
Dr. Cornforth, who was born in Australia, shared the Nobel Prize in Chemistry in 1975 and could trace that achievement to his discovery as a child that he was becoming deaf.
December 20, 2013, Friday
MORE ON NOBEL PRIZES AND: Deafness , Chemistry , Cornforth, John W (1917-2013) , Nobel Prizes , Deaths (Obituaries)
China Spins Mandela to Fit Its Political Narrative
In lionizing the former South African president, China's propaganda authorities have hopscotched over much of Mr. Mandela's life as they try to write him into a political narrative that burnishes the Communist Party's legitimacy.
December 12, 2013, Thursday
MORE ON NOBEL PRIZES AND: Liu Xiaobo , Mandela, Nelson , South Africa , China , Communist Party of China , Political Prisoners , Nobel Prizes , Human Rights and Human Rights Violations
From the Archives
Winners of the Nobel Prize in Literature
A complete list of winners of the Nobel Prize in Literature, with links to New York Times coverage.
Doris Lessing on the Nobel Prize
When reporters in 2007 told Ms. Lessing that she had won the Nobel Prize for literature, she said, "I couldn't care less."
Doris Lessing on the Nobel Prize
When reporters in 2007 told Ms. Lessing that she had won the Nobel Prize for literature, she said, "I couldn't care less."
Higgs Boson Particle Theory Wins Nobel
Dennis Overbye, a Times science reporter, discusses the Higgs boson particle's significance — and insignificance — in understanding our universe.
Gabriel García Márquez, Novelist and Exponent of Magic Realism
He erupted on the literary world stage with the 1967 appearance of "One Hundred Years of Solitude," which would sell more than 20 million copies.
TimesCast | Ending Liberia's Civil War
October 7, 2011 — Ellen Johnson Sirleaf, the current president, and Leymah Gbowee, a peace activist, were awarded the prize for their roles in moving the country beyond its violent past.
TimesCast | Ending Liberia's Civil War
October 7, 2011 — Ellen Johnson Sirleaf, the current president, and Leymah Gbowee, a peace activist, were awarded the prize for their roles in moving the country beyond its violent past.
TimesCast | Yemeni Woman Wins Nobel
October 7, 2011 — Tawakkol Karman was one of the first to lead antigovernment protests in Yemen.
TimesCast | Yemeni Woman Wins Nobel
October 7, 2011 — Tawakkol Karman was one of the first to lead antigovernment protests in Yemen.
TimesCast | October 7, 2011
Three women win the 2011 Nobel Peace Prize: Liberian president Ellen Johnson-Sirleaf, her compatriot Leymah Gbowee and Yemeni pro-democracy activist Tawakul Karman.
TimesCast | October 7, 2011
Three women win the 2011 Nobel Peace Prize: Liberian president Ellen Johnson-Sirleaf, her compatriot Leymah Gbowee and Yemeni pro-democracy activist Tawakul Karman.
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