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Study Shows Importance of Early End-of-Life Care Discussions
Patients with advanced cancer who discussed end-of-life care with their doctors earlier in the course of their illness had care that was less aggressive in their last month of life and were more likely to use hospice services, according to a new study. Earlier discussions may help to ensure that care at the end of life is more consistent with patients' preferences, the study authors explained. Yet, on average, these discussions took place about 1 month before a patient died, they found.
The study was published online November 13 in the Journal of Clinical Oncology (JCO). Read more > >
Drug May Reduce Cognitive Decline Following Radiation for Brain MetastasesMemantine may become standard treatment for patients receiving radiation to the brain
Brazil's Strong Antismoking Policies Credited with Saving LivesModel indicates nearly 420,000 deaths were averted by 2010
Possible Cause of Doxorubicin-Induced Heart Damage IdentifiedDiscovery may lead to less toxic drugs and tests to identify vulnerable patients
Study Reveals New Mechanism of Action for Class of Targeted TherapyFindings may influence use of this class of drugs in clinical trials
Also in the News: Radium-223 Improves Survival in Men with Metastatic Prostate Cancer
Also in the Journals: Genetic Factors Linked to Lung Cancer in Asian Women Who Have Never Smoked
NIH Research Radio: A Clinical Trial for HIV-Positive Cancer PatientsNCI Cancer Bulletin writer and editor Daryl McGrath talks about a phase II clinical trial exploring the safety of stem cell transplants for HIV-positive cancer patients
Type: (MP3) | Time 5:00 | Size: 5.7 MB | Read Transcript
Special Issue on the Science behind Cancer Screening
Don't miss our November 27 special issue, which will focus on the science behind cancer screening. In addition to commentary from some of the top experts in cancer screening, articles will look at addressing disparities, translating clinical trial findings into practice, and using modeling to determine who will benefit most from screening.Past special issues have focused on oncology nursing, obesity and cancer research, and adolescent and young adult cancers
Decades Later, Chernobyl Accident Yields Clues to Leukemia RiskLong-term study ties low doses of radiation to chronic lymphocytic leukemia
Featured Clinical Trial: Dietary Intervention for Patients Receiving Chemoradiotherapy for Lung CancerWill patients being treated for lung cancer safely tolerate a ketogenic diet?
DREAMing Big to Solve Cancer Research ChallengesThe NCI-DREAM competition uses crowdsourcing to tackle thorny problems
FDA Update
- New Treatment Approved for Chronic Myelogenous Leukemia
CDC Update
- Global Study Documents Tobacco Use, Secondhand Smoke Exposure among Women of Childbearing Age
Cancer.gov Update
- Newly Launched NCI Map Stories Show Geographic Patterns of Cancer
- National Cancer Advisory Board to Meet Later this Month
- NCI Workshop Will Address Scientific Priorities for Cancer Epidemiology
- CancerCare, NCI Seek Submissions for eHealth Video Challenge
- Cancer Research Network Scholars Program Accepting Applications
- Quit Smoking with Mobile Resources from NCI
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.
For more information about cancer, call 1-800-4-CANCER or visit http://www.cancer.gov.
NCI Cancer Bulletin staff can be reached at firstname.lastname@example.com.
Featured Article
Study Shows Importance of Early End-of-Life Care Discussions
Patients with advanced cancer who discussed end-of-life care with their doctors earlier in the course of their illness had care that was less aggressive in their last month of life and were more likely to use hospice services, according to a new study. Earlier discussions may help to ensure that care at the end of life is more consistent with patients' preferences, the study authors explained. Yet, on average, these discussions took place about 1 month before a patient died, they found.
The study was published online November 13 in the Journal of Clinical Oncology (JCO).
Although some patients may wish to have aggressive care at the end of life, "most patients who recognize that their cancer is terminal want to receive less-aggressive care," the study's lead investigator, Dr. Jennifer Mack of the Dana-Farber Cancer Institute, said in a news release.
The American Society of Clinical Oncology and other groups recommend that discussions about palliative and end-of-life care begin shortly after a patient has been diagnosed with advanced cancer. Several studies have found that such discussions between physicians and patients with advanced cancer are often delayed until late in a patient's life, if they take place at all.
For example, an earlier study by Dr. Mack and her colleagues found that oncologists had end-of-life care discussions with only about one-quarter of their patients, and, when the end-of-life care discussions took place, they often happened in the hospital during episodes of acute care.
In the new study, researchers analyzed patient (or patient surrogate) interviews and the medical records of more than 1,200 patients with end-stage lung or colorectal cancer regarding discussions about end-of-life care, including resuscitation and hospice care. All patients in the study lived for at least 1 month after diagnosis and were participants in the NCI-funded Cancer Care Outcomes Research and Surveillance Consortium.
Almost half of the patients had at least one form of aggressive care in the last month of their lives: 16 percent of patients underwent chemotherapy within the last 2 weeks of life, 40 percent received acute care in the hospital within the last 30 days of life, and 6 percent were treated in the intensive care unit in the last 30 days of life.
—Dr. Jennifer Mack
Patients who had end-of-life care discussions earlier, however, were much less likely to receive aggressive care and more likely to receive hospice care.
The results "really highlight that much more work needs to be done to address this long-standing problem," said Dr. Ann O'Mara, a program director in NCI's Division of Cancer Prevention who leads the institute's palliative care research program.
In a March 2012 interview with the NCI Cancer Bulletin, Dr. Thomas Smith, director of palliative care for the Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, noted that discussions about palliative care should begin shortly after diagnosis, even with patients who do not have a terminal cancer. However, these discussions are particularly important for patients with incurable cancers, he said.
"Most [oncologists] choose not to have discussions about things like hospice, do-not-resuscitate [orders], and advance medical directives until there are no more chemotherapy options left," he said. "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."
Less-aggressive care near the end of life can clearly benefit patients and their families, Dr. Mack commented.
Aggressive end-of-life care has been linked to a higher risk of depression among caregivers after the patient has died, she explained. And for patients, less-aggressive care can mean "a better quality of life in their final days, because there is a greater focus on symptom management and they are more often able to receive care in their homes," she said.
Now that several studies (for example, here and here) have documented that earlier palliative care can improve patients' quality of life and, in some cases, may have improved survival, Dr. O'Mara believes the time is ripe for "an intervention trial that examines the timing and frequency of doctor-patient conversations and the impact they have on patients and families," particularly with regard to care decisions and their psychosocial impact on family members and caregivers.
This research was supported by grants from the National Institutes of Health (U01 CA093344, U01 CA093332, U01 CA093324, U01 CA093348, U01 CA093329, U01 CA093339, and U01 CA093326).
Further reading: "Last Days of Life" and "Palliative Care Improves Survival, Quality of Life in Advanced Lung Cancer"
Cancer Research Highlights
Drug May Reduce Cognitive Decline Following Radiation for Brain Metastases
A drug already approved to help improve cognition in some patients with dementia may limit declines in memory and cognitive function in patients who are undergoing whole-brain radiation therapy (WBRT) to treat cancer that has spread to the brain. Results from a clinical trial to test the drug, memantine (Namenda), in patients with brain metastases were presented October 28 at the American Society for Radiation Oncology (ASTRO) annual meeting.
More than 60 percent of patients with brain metastases who undergo WBRT experience problems with cognitive function within 4 months after completing treatment, explained the trial's lead investigator, Dr. Nadia Laack of the Mayo Clinic Cancer Center, during a press briefing. The intent of the NCI-supported trial was to determine whether memantine could prevent memory decline in patients, rather than to test whether the drug improved progression-free or overall survival, Dr. Laack noted.
The phase III randomized trial, conducted by the Radiation Therapy Oncology Group and dubbed RTOG-0614, enrolled more than 550 patients, who received either memantine or a placebo during WBRT and for 6 months afterward. The researchers assessed participants' memory and other cognitive functions, such as the ability to process information and make decisions, before and after treatment. Many patients in the trial died or had cancer that continued to progress, however, so after 24 weeks only 149 patients could be evaluated.
Patients whose disease progressed "often refused testing so, in effect, we were largely evaluating patients who had not progressed," Dr. Laack explained in an e-mail message.
In patients treated with memantine, memory decline took longer to appear and was less severe, although the improvement was not statistically significant. However, the risk of cognitive decline fell 17 percent, a drop that was statistically significant.
"Although memantine was discontinued at 6 months, the effect on cognitive function was maintained for the duration of the trial, suggesting that memantine may be preventing radiation injury rather than simply treating cognitive dysfunction," Dr. Laack said.
Based on the trial's results, memantine will likely now be used as standard therapy for patients undergoing WBRT to treat brain metastases, she added. "We do feel that this is going to impact practice tomorrow and that, for future trials, memantine will be the standard against which other agents are tested."
This study was funded in part by the National Institutes of Health (CA21661, CA32115 and CA37422, RTOG U10 CA21661, and CCOP U10 CA37422).
Brazil's Strong Antismoking Policies Credited with Saving Lives
Using a policy simulation model called SimSmoke, researchers have estimated that strong tobacco control policies implemented in Brazil between 1989 and 2010 cut the smoking rate nearly in half and saved almost 420,000 lives during that period. Dr. David Levy of Georgetown University's Lombardi Comprehensive Cancer Center and his colleagues published their findings November 6 in PLOS Medicine.
Using SimSmoke, the researchers looked at the effects of various tobacco control policies on the smoking rate in Brazil, which declined from 34.8 percent in 1989 to 18.5 percent in 2008. SimSmoke models the effects of tobacco control policies on smoking initiation and cessation rates and uses the changes in these rates to estimate smoking rates over time.
The Brazil SimSmoke model showed that almost half of the 46 percent reduction between 1989 and 2010 was due to tobacco tax and price hikes. Smokefree air laws, restrictions on advertising, programs to help people quit smoking, media campaigns, and mandatory health warnings on tobacco packaging also contributed to the drop in smoking rates.
"This study indicates how powerful tobacco control policies are," said Dr. Levy.
Brazil's current tobacco control policies are projected to reduce the smoking rate from 16.8 percent in 2010 to 10.3 percent in 2050 and prevent an estimated 7 million premature deaths due to smoking. The model also showed that, if Brazil fully implemented policies recommended by the World Health Organization's Framework Convention on Tobacco Control, the country's smoking rate would fall to 6.3 percent by 2050, preventing 1.3 million more deaths.
"Brazil's accomplishments demonstrate that, even for a middle-income nation, reducing tobacco use is a 'winnable battle' that carries huge dividends in terms of reducing mortality and morbidity," the researchers wrote.
"There is now a 'global laboratory' of tobacco control," said Dr. Michele Bloch, acting chief of NCI's Tobacco Control Research Branch. "Studies from around the world allow countries to benefit from each other's experience."
This study was funded in part by the National Institutes of Health (UO1-CA97450-02).
Possible Cause of Doxorubicin-Induced Heart Damage Identified
The damage to heart tissue (cardiotoxicity) sometimes seen with the drug doxorubicin may be caused by the chemotherapy's effects on an enzyme called topoisomerase-IIβ (Top2β). This finding, from experiments in mice led by Dr. Sui Zhang of the University of Texas MD Anderson Cancer Center, was published October 28 in Nature Medicine.
The results suggest that Top2β is "an essential driver of doxorubicin-induced cardiotoxicity," the authors concluded. This knowledge could lead to the development of drugs that are less cardiotoxic than doxorubicin, as well as to tests that identify patients who are most at risk for heart damage associated with this drug, they said.
Doxorubicin's anticancer effects are thought to be caused by its interactions with a related enzyme, called topoisomerase-IIα (Top2α). This enzyme is expressed in rapidly dividing cells, including cancer cells, but not in mature, nondividing cells. Top2β, on the other hand, is found in all cells, and the highest levels are found in mature cells.
Because doxorubicin also interacts with Top2β, the researchers proposed that the drug might damage mature heart muscle cells through its effects on this enzyme. For their experiments, the researchers genetically engineered mice to have heart muscle cells that did not express Top2β.
When normal mice were exposed to doxorubicin, the researchers found changes in the gene expression of heart-muscle cells that were not found when mice with Top2β-deficient hearts were treated with the drug. Many of the changes occurred in cellular signaling pathways that regulate cell death (apoptosis) and the functioning of mitochondria, structures inside cells that produce most of the energy cells use.
When researchers measured the level of apoptosis in heart muscle cells to assess doxorubicin-induced damage to the heart, Top2β-deficient hearts had 70 percent fewer dying heart muscle cells than normal hearts after doxorubicin treatment. Moreover, mice with Top2β-deficient hearts had no decrease in heart function after 5 weeks of doxorubicin, whereas heart function in normal mice fell by 10 percent.
Drugs that specifically target Top2α and not Top2β "should be less cardiotoxic and, hence, more useful clinically," they continued. And measuring Top2β expression could identify patients more likely to experience heart damage from doxorubicin. "These predictions can be tested in animals and humans," they concluded.
This study was funded in part by the National Institutes of Health (CA102463).
Study Reveals New Mechanism of Action for Class of Targeted Therapy
Researchers have discovered a new way in which PARP inhibitors block cancer cell growth. The researchers also have found that three experimental PARP inhibitors, which were presumed to have similar activities, vary widely in their ability to kill cancer cells. The study, led by Dr. Yves Pommier of the Laboratory of Molecular Pharmacology in NCI's Center for Cancer Research, was published November 1 in Cancer Research.
PARP inhibitors have shown promising anticancer activity against breast and ovarian cancers in women with BRCA1 or BRCA2 gene mutations. The drugs were believed to block cancer cell growth by inhibiting the activity of PARP proteins, which help repair damaged DNA. Therefore, drugs with similar levels of PARP inhibition should have comparable anticancer effects. However, studies have indicated that treating cells with a PARP inhibitor causes more toxicity than would be achieved simply by loss of PARP activity, suggesting that these drugs may have a second mechanism of action.
The researchers showed that PARP inhibitors can also trap PARP proteins at sites of DNA damage, forming PARP-DNA complexes that are toxic to cells. The strength of the trapped PARP-DNA complexes correlated with a drug's ability to kill cancer cells and varied widely between the three tested PARP inhibitors, which are currently being studied in clinical trials.
"While PARP inhibitors had been assumed to be of equivalent potency based on the degree to which they elicit PARP inhibition, we now know that they are not equivalent with respect to their potency to trap PARP," said Dr. Pommier in a news release.
The new study also showed that PARP inhibition and PARP trapping are not directly related. Olaparib (AZD2281) was the most potent PARP inhibitor followed by veliparib (ABT-888) and then niraparib (MK-4827).
In contrast, cells treated with niraparib or olaparib formed the most potent PARP-DNA complexes. When combined with a DNA alkylating agent, niraparib and olaparib also were much more toxic to cancer cells than veliparib.
"Our findings suggest that clinicians who use PARP inhibitors in clinical trials should carefully choose their drug, because we now suspect results may differ, depending upon the PARP inhibitor used," said first author Dr. Junko Murai, in a news release.
The researchers also investigated the effects of these PARP inhibitors on 30 cell lines that had different DNA repair genes inactivated. The results confirmed that cells without BRCA1 or BRCA2 function are more sensitive than normal cells to PARP inhibition. The study also revealed other genes not previously implicated in sensitizing cells to PARP inhibitors. These results may help determine which tumors are most likely to be susceptible to PARP inhibition.
This work was supported by NCI's Intramural Research Program.
Also in the News: Radium-223 Improves Survival in Men with Metastatic Prostate Cancer
Final data from a trial involving men with castrate-resistant prostate cancer that had spread to the bones showed that radium-223 (Alpharadin) improved overall survival by more than 3 months. Radium-223, part of a class of drugs called alpha-particle emitters, targets bone metastases.
The final results from the ALSYMPCA trial were presented October 28 at the American Society for Radiation Oncology annual meeting.
Overall survival in the final analysis of the trial was 14.9 months for men who received radium-223 compared with 11.3 months for men who received a placebo, a slight improvement over the findings of an interim analysis presented earlier this year.
Men treated with radium-223 also lived nearly 40 percent longer without having a skeletal-related event, such as a bone fracture or spinal cord compression, or the need for radiation therapy to treat symptomatic bone metastases.
Also in the Journals: Genetic Factors Linked to Lung Cancer in Asian Women Who Have Never Smoked
Researchers have identified three more regions of the genome that may play a role in the development of lung cancer in Asian women who have never smoked. One variant is on chromosome 10 and two are on chromosome 6. The study also confirmed previous reports linking regions of chromosomes 5, 3, and 17 to lung cancer in Asian women who have never smoked.
Women with one of the three newly identified genetic variants may be more susceptible to lung cancer caused by environmental exposures, including secondhand smoke, the researchers found, although this needs to be replicated in other studies. Contrary to previous research, this study found no evidence that a variant on chromosome 15 is associated with lung cancer in Asian women who have never smoked, which suggests that this variant may be smoking related.
The genome-wide association study included data from 14 studies and compared the genomes of 6,600 Asian women with lung cancer and 7,500 without lung cancer. Dr. Qing Lan of NCI's Division of Cancer Epidemiology and Genetics and her colleagues published their findings November 11 in Nature Genetics.
This study was supported by the National Institutes of Health (ZIACP010121).
NIH Research Radio: A Clinical Trial for HIV-Positive Cancer Patients
NCI Cancer Bulletin writer and editor Daryl McGrath talks about a phase II clinical trial exploring the safety of stem cell transplants for HIV-positive cancer patients
Type: (MP3) | Time: 5:00 | Size: 5.7 MB | Read Transcript
Special Report
Decades Later, Chernobyl Accident Yields Clues to Leukemia Risk
Exposure to low doses of ionizing radiation over extended periods of time may raise the risk of chronic lymphocytic leukemia (CLL), as well as other types of leukemia, later in life, new research suggests. The findings are from a study of Ukrainian workers who were exposed to radiation while cleaning up the 1986 Chernobyl nuclear power plant accident.
Twenty years after the disaster, these workers, as a group, had an increased risk of CLL and other forms of leukemia, researchers reported online last week in Environmental Health Perspectives. The case-control study used information from a larger study tracking the health of more than 110,000 Chernobyl cleanup workers.
"Previous research has shown an increased risk of some types of leukemia related to radiation exposure," said lead researcher Dr. Lydia Zablotska of the University of California, San Francisco. "However, none of those studies have reported an association for CLL, so we were intrigued by our findings."
In the new study, Dr. Zablotska's team attributed 19 of 117 cases of leukemia (16 percent) diagnosed in the cleanup workers since the Chernobyl nuclear reactor accident to radiation exposure from the accident. The magnitude of risk was similar for CLL and for other types of leukemia.
CLL is more common than other leukemias in the United States, with some 15,000 cases diagnosed last year. The disease is a relatively benign leukemia, but some patients require chemotherapy and the cancer can be fatal.
In addition to providing clues about the causes of CLL, the new findings could help researchers understand the long-term health effects of exposure to low-dose radiation. "The radiation burden in the United States has increased over the past 20 years, primarily from exposure to CT scans," said Dr. Zablotska. "We want to know what this radiation can do in the long term."
Radiation can cause damage to DNA that eventually leads to cancer. Studies of atomic bomb survivors have documented the cancer risks associated with short-term exposure to moderate and high doses of radiation. Less is known, however, about the health effects of exposure to lower doses of radiation over a longer period of time, such as the doses experienced by the cleanup workers.
In 2008, the research team first reported an association between radiation exposure and CLL in Chernobyl cleanup workers. Because the finding was unexpected, the authors undertook the current study with a larger sample and longer follow-up.
"For researchers, these findings are exciting because they could open up new research into the mechanism of how CLL develops," said Dr. Kiyohiko Mabuchi, who heads the Chernobyl Research Unit in NCI's Division of Cancer Epidemiology and Genetics and is the senior author of the new study.
He noted that other studies of radiation-exposed workers have not detected an increased risk of CLL, so more research is needed to understand these inconsistencies. Identifying the biological mechanism underlying the association will be important, he added.
This study provides "some of the most substantial evidence to date supporting the conclusion that developing CLL is a possible adverse consequence of exposure to ionizing radiation," noted Dr. David Richardson, an epidemiologist at the University of North Carolina, Chapel Hill, who studies the health effects of radiation but was not involved in the research.
"It will be important to continue to monitor health consequences," added Dr. Mabuchi, "both in cleanup workers, as well as in other groups exposed to radiation from the Chernobyl accident."
This research was supported by NCI's Intramural Research Program.
Featured Clinical Trial
Dietary Intervention for Patients Receiving Chemoradiotherapy for Lung Cancer
Name of the Trial
Phase I Trial of a Ketogenic Diet with Concurrent Chemoradiation for Non-Small Cell Lung Cancer (KETOLUNG; NCT01419587). See the protocol summary.
Principal Investigators
Drs. Sudershan K. Bhatia, Daniel James Berg, John Michael Buatti, and Douglas R. Spitz, University of Iowa Holden Comprehensive Cancer Center
Why This Trial Is Important
One of the fundamental differences between cancer cells and normal cells is in how they break down (metabolize) nutrients to obtain the energy they need to grow and survive. Normal cells typically rely on oxidative metabolism of glucose, fatty acids, or amino acids to produce energy. In this process, which takes place inside cellular structures called mitochondria, chemical reactions that require oxygen are used to maximize the amount of energy produced from each molecule being metabolized.
Cancer cells, on the other hand, have defects in mitochondrial oxidative metabolism, leading to excess production of potentially harmful molecules known as reactive oxygen species. This can create a condition called metabolic oxidative stress. To compensate for this defect in mitochondrial metabolism, cancer cells use mitochondrial oxidative metabolism, as well as another metabolic process called glycolysis, to break down glucose.
Cancer cells are believed to use much more glucose than normal cells because, in addition to using it for energy production, cancer cells can use the products of glucose metabolism to detoxify reactive oxygen species. Researchers are exploring ways that this difference in cellular metabolism between cancer cells and normal cells might be exploited to selectively kill cancer cells.
Carbohydrates in the diet provide a readily available supply of glucose that can be used to fuel cancer cell growth. Therefore, one method being investigated is the use of a specialized diet that dramatically reduces the amount of glucose in the blood, called a ketogenic diet. This type of diet has been used for decades to help children and young adults with treatment-resistant epilepsy that causes grand mal seizures.
Ketogenic diets are so named because they force the body into a starvation-like state called ketosis, in which the liver converts fats into molecules called ketones that circulate in the blood and can serve as mitochondrial energy sources for certain tissues. Ketogenic diets, therefore, restrict the amount of glucose available to cancer cells and force them to rely more heavily on oxidative metabolic pathways that might selectively induce oxidative stress in cancer cells.
"We're interested in a ketogenic diet for cancer therapy because it limits glucose metabolism and emphasizes oxidative metabolism of fatty acids, ketone bodies, and amino acids in mitochondria. We think that mitochondria from tumor cells produce more superoxide and hydrogen peroxide [two types of reactive oxygen species] than mitochondria from normal cells," said Dr. Spitz. "Consuming a ketogenic diet should therefore selectively enhance the sensitivity of tumor cells to treatments that increase oxidative stress, such as radiation and chemotherapy."
Radiation therapy is thought to kill cancer cells by generating free radicals that cause oxidative stress, and this can be enhanced by the simultaneous use of chemotherapy (chemoradiation). "If oxidative stress is selectively enhanced in cancer cells by the ketogenic diet, the reactive oxygen species produced by the radiation and chemotherapy can more effectively damage DNA, proteins, and other critical biomolecules in the cancer cell and improve cancer cell killing, as well as improving therapeutic outcome," he explained.
In this phase I clinical trial, patients with stage III or IV (with limited metastasis) non-small cell lung cancer who are about to undergo chemoradiation therapy will consume a ketogenic diet for the duration of their treatment. Doctors will assess the safety and tolerability of the diet in conjunction with chemoradiation treatment, as well as measure the levels of glucose and ketones in the blood and oxidative stress markers in plasma and urine.
About 90 percent of calories in the ketogenic diet used in this study come from fat, whereas less than 2 percent of calories come from carbohydrates, with protein supplying the remaining calories. Participants will consume specially formulated shakes in the morning and work with a dietician to maintain a similar calorie balance throughout the day. They will begin the ketogenic diet 48 hours before the initiation of chemoradiation therapy and continue through the end of the 6- to 7-week treatment period.
"An excellent example of the role of increased glucose metabolism in cancer is the FDG-PET scan," said Dr. Bhatia. "We use PET scans with all of our lung cancer patients as part of our diagnostic and staging tests. At a fundamental level, the PET scan is done using glucose with a radioactive tag (18F-FDG) injected into the patient, and that glucose lights up the area of tumor cells because of their metabolic pathway. That's how we determine where the tumor is and, in metastatic disease, where the cancer has spread. With this diet, we hope to deprive the tumor of the glucose it depends on for energy as well as enhance oxidative stress."
This study, as well as a similar study for pancreatic cancer patients, is being conducted at the University of Iowa's Holden Comprehensive Cancer Center.
For More Information
See the lists of eligibility 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.
Community Update
DREAMing Big to Solve Cancer Research Challenges
Earlier today, at the DREAM7 Conference in San Francisco, representatives from the two best-performing teams in the NCI-DREAM Drug Sensitivity Prediction Challenge took to the stage to unveil their methods. Members of the two teams, from Helsinki, Finland, and Dallas, TX, along with 50 other teams from around the world, spent several months this year putting their heads together to work on two related scientific challenges.
NCI-DREAM is part of a larger project known as DREAM (Dialogue for Reverse Engineering Assessments and Methods). Now in its seventh year, DREAM is one of a growing number of biomedical research endeavors that take advantage of crowdsourcing—outsourcing a task to a group or community through an open call or contest.
NCI partnered with DREAM to support innovative approaches to cancer research and to capitalize on the breadth of knowledge of the research community to develop better treatments for cancer patients.
Crowdsourcing "takes advantage of the strength of the broader community to expand our understanding of some difficult scientific problems," noted Dr. Dan Gallahan, deputy director of NCI's Division of Cancer Biology and one of the organizers of the NCI-DREAM challenge.
"The project was born to try to help the research community understand the limitations and strengths of our own methods," explained Dr. Gustavo Stolovitzky, an IBM computational biologist who has been a driving force behind the project. "Crowdsourcing also allows us to determine what the best method is for the solution that we are seeking."
Solve This!
Participants in the two-part challenge were asked to use a vast array of genomic information to build computer models that can predict the sensitivity of cancer cell lines to a set of small-molecule compounds or combinations of compounds. The goal of sub-challenge 1 was to predict the sensitivity of 18 breast cancer cell lines to 31 previously untested compounds, while the goal of sub-challenge 2 was to predict the activity of pairs of compounds on a diffuse large B-cell lymphoma (DLBCL) cell line.
Genomic data for NCI-DREAM were provided by Dr. Joe Gray of Oregon Health and Science University and Dr. Andrea Califano of Columbia University.
"Drug sensitivity prediction from genomic profiles is the core problem of personalized cancer medicine…. At the same time, the task is fascinating due to the challenges it poses [for] computational analysis," wrote Dr. Elisabeth Georgii, a postdoctoral researcher at Helsinki Institute for Information Technology HIIT, Aalto University, in an e-mail message. Dr. Georgii is representing TeamFIN, the best-performing team in sub-challenge 1.
The best-performing team in sub-challenge 2 hails from the University of Texas Southwestern (UTSW) Medical Center. Dr. Yang Xie, an assistant professor in the Department of Clinical Sciences at UTSW, is representing her team at the meeting. (A complete list of members from the best-performing DREAM challenge teams is available online.)
The More the Merrier
In addition to a speaking invitation and travel expenses to the DREAM7 Conference in San Francisco for a team representative, the best-performing teams will publish a peer-reviewed Nature Biotechnology paper on the sub-challenge in which their method was the best performer.
—Dr. Gustavo Stolovitzky
"Incentives can go a long way to gather more people who try to solve the challenge. And if more people participate, it's more likely that we will find a method that will really hit the nail on the head," Dr. Stolovitzky noted.
The long-term goal of NCI-DREAM is to apply what was learned from the challenge to improve treatments for cancer patients. "This is the start of being able to make predictions of how to treat a patient based on his or her molecular profile," Dr. Gallahan explained. With that goal in mind, NCI plans to support the subsequent experimental validation and development of the top performing models in the challenge.
"Cancer is such a complex disease that we want to engage as many people in cancer research as possible" he continued. "And if crowdsourcing is one way that we can do that, then that's another tool in our arsenal."
Collaborating to Improve Predictions of Breast Cancer Prognosis
The DREAM7 Conference also featured the Sage Bionetworks-DREAM Breast Cancer Prognosis Challenge. The goal of this ongoing challenge is to assess the accuracy of computational models designed to predict breast cancer survival, based on clinical information about the patient's tumor as well as genome-wide molecular profiling data.
The challenge, run by Seattle-based Sage Bionetworks in collaboration with the DREAM Project, is an open computational challenge whose initial, model-building phase used genomic and clinical data from 2,000 women diagnosed with breast cancer. The challenge drew 354 participants—teams and individuals—from more than 35 countries.
Sage Bionetworks is supported in part by the Integrative Cancer Biology Program in NCI's Division of Cancer Biology.
"The Breast Cancer Challenge is an opportunity to leverage the crowd…and demonstrate what happens when you ask researchers to work together rather than on their own," said Dr. Thea Norman, director of strategic development for Sage Bionetworks. Ultimately, she noted, Sage Bionetworks hopes to organize challenges that improve patients' lives.
In the final phase of the challenge (expected to end by early 2013), the model that most accurately predicts survival when tested against a novel validation dataset of molecular and clinical data from approximately 250 breast cancer patients will be declared the winner.
Representatives of the two best-performing teams during the model-building phase—Columbia University's Attractor Metagenes and the University of Pittsburgh's PittTransMed—were awarded travel expenses and will speak at the DREAM7 Conference. The overall winner or winners of the challenge will publish their results in Science Translational Medicine.
FDA Update
New Treatment Approved for Chronic Myelogenous Leukemia
The Food and Drug Administration has approved omacetaxine mepesuccinate (Synribo) to treat adults with chronic myelogenous leukemia (CML) whose cancer has progressed after treatment with at least two tyrosine kinase inhibitors (TKIs).
Omacetaxine mepesuccinate interferes with the ability of cancer cells to make proteins. The drug is injected just under the skin twice daily for 14 consecutive days over a 28-day cycle until white blood cell counts return to normal. It is then administered twice daily for 7 consecutive days over a 28-day cycle as long as patients continue to benefit.
The drug's effectiveness was evaluated using a combined cohort of patients whose cancer progressed after previous treatment with two or more TKIs. All of the patients were treated with omacetaxine mepesuccinate.
In 14 of 76 patients with chronic phase CML (18.4 percent), the percentage of cells expressing the Philadelphia chromosome genetic mutation fell within 3.5 months, on average. The median duration of the reduction was 12.5 months.
In 5 of 35 patients with accelerated phase CML (14.3 percent), white blood cell counts normalized or the patient had no evidence of leukemia, within 2.3 months, on average. The median duration of the response in these patients was 4.7 months.
The most common side effects reported during the clinical studies included a low level of platelets in the blood; a low red blood cell count; a decrease in neutrophils, which may lead to infection, fever, diarrhea, nausea, weakness, and fatigue; a reaction at the injection site; and a drop in lymphocytes in the blood.
Omacetaxine mepesuccinate was approved under the FDA's accelerated approval program, which provides patients access to promising new drugs while the company conducts additional clinical studies to confirm the drug's clinical benefit and safe use. The drug also received orphan-product designation by the FDA because it is intended to treat a rare disease or condition.
CDC Update
Global Study Documents Tobacco Use, Secondhand Smoke Exposure among Women of Childbearing Age
In low- and middle-income countries around the world, the prevalence of smoking and other forms of tobacco use among women of reproductive age varies greatly, but heavy exposure to secondhand smoke is common, according to a new study by researchers from the Centers for Disease Control and Prevention (CDC) and the World Health Organization.
The findings were published November 2 in Morbidity and Mortality Weekly Report.
The researchers, led by Van Tong of the CDC, looked at data from the 2008–2010 Global Adult Tobacco Survey on women aged 15 to 49 in 14 different countries. Overall, the analysis showed that 92 million women were current users of tobacco products; smokeless tobacco use was rare, except in Bangladesh and India.
Smoking rates among women in this age group were extremely low in some countries (less than 1 percent in Egypt and Bangladesh) but high in others (about 30 percent in Russia and Poland). Exposure to secondhand smoke was common; about half the women of reproductive age in these 14 countries—nearly 470 million women—were exposed to secondhand smoke in their homes. This exposure varied widely, however, ranging from about 18 percent in Mexico and 26 percent in Ukraine to more than 60 percent in China, Egypt, Turkey, and Vietnam.
"An estimated 62 million births occur annually in these 14 study countries, highlighting the need to protect reproductive-aged women from the harms of tobacco and to promote their health and the well-being of their children," the researchers wrote.
The World Health Organization Framework Convention on Tobacco Control requires countries participating in the treaty to implement evidence-based strategies to reduce tobacco use, including raising prices and taxes on tobacco products, protecting people from exposure to secondhand smoke, enforcing bans on advertising and promoting tobacco products, and providing cessation assistance. These strategies, the authors noted, can prevent or reduce tobacco use and secondhand smoke exposure among reproductive-aged women.
Cancer.gov Update
Newly Launched NCI Map Stories Show Geographic Patterns of Cancer
NCI's Geographic Information Systems (GIS) & Science website now features a series of interactive maps called NCI Map Stories. The series uses web-based mapping technologies to create narratives about geographic patterns of cancer.
The first Map Story, released in October during Breast Cancer Awareness Month, includes maps showing the most recent breast cancer incidence and mortality rates in the United States. Users can zoom in on the maps to compare incidence and mortality by state and download the data in tables or in PDF format.
Lung, cervical, and colorectal cancer maps are planned for the coming months, and new Map Stories will be released to coincide with national cancer awareness months.
National Cancer Advisory Board to Meet Later this Month
The National Cancer Advisory Board (NCAB) will meet November 28–30 on the NIH main campus in Bethesda, MD.
The agenda will be available on the NCAB website soon, and the proceedings will be broadcast live online. An archived videocast will be available a few days after the meeting, which will be held in Building 31.
Videocasts of past meetings are available here.
NCI Workshop Will Address Scientific Priorities for Cancer Epidemiology
NCI will hold a workshop December 12 and 13 to help develop scientific priorities for cancer epidemiology research in the next decade. NCI's Epidemiology and Genomics Research Program (EGRP) recently launched a strategic planning effort and is soliciting input on the major questions facing cancer epidemiology research.
Workshop panelists will include prominent cancer researchers, as well as leaders from other NIH institutes and centers. NCI leaders Drs. Robert Croyle, Barry Kramer, Debbie Winn, Stephen Chanock, Robert Hoover, and Patricia Hartge plan to attend. Dr. Michael Lauer, a division director at the National Heart Lung and Blood Institute, will also participate.
The workshop, "Trends in 21st Century Epidemiology: From Scientific Discoveries to Population Health Impact," will be held in Bethesda, MD. Those who cannot attend in person can view a videocast of the workshop and join a LinkedIn and Twitter chat. In preparation for the workshop, EGRP has blogged about topics related to the workshop sessions. Comments from researchers and other interested individuals are welcome.
CancerCare, NCI Seek Submissions for eHealth Video Challenge
Cancer patients, survivors, and their families and friends are invited to submit videos to the eHealth Video Challenge about how they are using information technology to better manage their cancer care, including their treatments and support. The Department of Health and Human Services' Office of the National Coordinator for Health Information Technology established the challenge to encourage the use of consumer e-health tools and other health information technologies.
Some examples of ways that patients are using health IT to be more engaged include
- Using the web to learn more about a diagnosis and relevant treatment options;
- Participating in an online community to connect with other patients and caregivers for support;
- Tracking and managing care and side effects using a personal health record to track and manage care received and side effects; and
- Using other electronic tools to determine the best treatment plans or to help manage medications, diet, or other activities to enhance cancer treatment, transitional care, and quality of life.
By participating in this challenge, people with cancer have an opportunity to inspire and motivate others with their stories. The project has the potential to improve patients' communication and collaboration with members of their health care teams and to help them better manage their cancer-related care.
The deadline for submissions is December 12. Find more information about the challenge online, and read a blog about online cancer resources.
Cancer Research Network Scholars Program Accepting Applications
The Cancer Research Network (CRN) Scholars Program is accepting applications for the next round of training, which will begin in March 2013.
CRN is a consortium of nine nonprofit research centers based in health care delivery organizations that supports research at the population level. The CRN Scholars Program consists of 26 months of training that aims to help junior investigators develop research independence. Trainees will use CRN resources to conduct population-based, multisite, and multidisciplinary studies.
The program is open to junior investigators from academic institutions, cancer centers, and other research centers. Applications are due December 15.
The CRN fosters scientific and resource development in areas such as prevention and screening, epidemiology of cancer, prognosis and outcomes, health care quality and cost, communications and dissemination/implementation, and informatics. (More information can be found here.)
To learn more about the program and for application materials, visit the website or contact Program Coordinator Sarah McDonald or Program Co-Directors Drs. Diana Buist or Terry Field.
Quit Smoking with Mobile Resources from NCI
NCI has added a new app to its collection of tools and resources to help people quit smoking. NCI QuitPal, a free app for iPhone or iPad, puts proven quit strategies and tools at smokers' fingertips, whenever they need them.
The app contains more than 10 interactive features that allow users to set a quit date and financial goals and to receive reminders. NCI QuitPal also
- Tracks daily smoking habits with an easy-to-use calendar;
- Includes motivational reminders that coincide with progress;
- Sends health milestones and craving tips;
- Allows users to connect with social networks and view personalized video messages from loved ones; and
- Makes it easy to access NCI's free Cancer Information Service by phone or live chat.
To download the app, search "NCI QuitPal" at the App Store or visit the Smokefree.gov website.
NCI has a number of other mobile resources to help people quit smoking, including SmokefreeTXT, SmokefreeTXT en Español, QuitSTART for teens, and the Quit Guide app.
NCI recently released the Quit Guide app for Android. Users who download the Quit Guide from Amazon, Google Play, or iTunes will get insight into what to expect and how to deal with problems that come up during the journey to becoming smokefree.


text:
Here's a movie about an apocalyptic scenario. It's from New Zealand!
The Quiet Earth (1985)
The world ends...OR DOES IT???
A guy wakes up one morning, and his city is totally abandoned. Not a soul in sight, he wanders around for a while wondering what happened. Eventually, we learn that he's some kind of scientist, and MAY have in some way been responsible for whatever calamity has befallen the human race. However, before any of those details are revealed, we're given a little bit of fun time with our hero, as he lives it up as The Last Man on Earth. He moves into someone's mansion; loots the city of whatever he wants; sets up generators and fancy stereo systems to keep busy....At one point, he sort of loses his mind, and roams around the city dressed as a woman (wouldn't YOU?).
Of course, such shenanigans grow tiresome after a while, so two additional characters are introduced in good order. Seems they also survived the disaster, and our hero, the scientist, begins to investigate why. From then on, The Quiet Earth loses some of its magic, and turns into a typical sci-fi, man-messing-with-forces-he-shouldn't scenario. WHY did everyone suddenly disappear? CAN our hero reverse the process? WILL the world be saved??? Although it's a bit dated, The Quiet Earth is still a fairly compelling story, and I actually liked it quite a lot until the third act, when the "suspense" kicks in. At that point, the film stops being fun, and gets too serious.
Something this small is better off just sticking to its central concept (Last Man on Earth), and leaving the broader questions unanswered. We don't need to know whether this guy can stop the world from blowing up, or how he was involved in causing the problem to begin with -- a movie like this can't really handle such issues properly. The conflict that unfolds between our hero and the other two characters would have been enough drama to sustain our interest for 90 minutes; I didn't need to see an explosion in the end.
3 out of 5.

subset: commoncrawl


text:
Brierley Hill / Amblecote, Cowslip Walk - 2 bed - £99,950 - Taylors - Brierley Hill
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Brierley Hill / Amblecote, Cowslip Walk £99,950
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Bedrooms: 2
Enjoying a position just off Stamford Road, this WELL PRESENTED AND MOST APPEALING, TWO BEDROOM, MEWS STYLE HOME should prove of interest to first time buyers, with a GAS CENTRALLY HEATED AND DOUBLE GLAZED layout comprising: Pleasant Sitting Room, Splendid Kitchen, Two Good Double Bedrooms and Delightful White Bathroom. Foregarden, Enclosed Rear Garden and REAR DRIVE parking. NO UPWARD CHAIN. EPC Rating D. BRIERLEY HILL OFFICE 01384 265265.
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14 Cowslip Walk Oct 19 2007 £129,000
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This is beautiful tree (pronounced si-zig-ee-um) is home to many birds and insects, but invasive in the Betty's Bay area of the Western Cape. An evergreen, water-loving tree, which grows to a height of 8 -15 m. This tree is often found near streams, on forest margins or in swampy spots. The leaves are elliptic to circular, bluish green on top and a paler green below. Young leaves are reddish. The white to pinkish fragrant flowers are borne in branched terminals and have numerous fluffy stamens and produce abundant nectar. It flowers from August to November. The fruits are oval berries, red to dark-purple when ripe.
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Gake no ue no Ponyo posterCopyright by respective production studio and/or distributor. Intended for editorial use only.
Directed by: Hayao Miyazaki
Cast: Matt Damon, Cate Blanchett, Tina Fey, Yuki Amami, Jôji Tokoro, Tomoko Yamaguchi, Kazushige Nagashima, Noah Lindsey Cyrus, Hiroki Doi, Yuria Nara


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Daniel Byrnes Band @ the Falmouth BBC
When: Thu Dec 6th
9:00 pm - 1:00 am
Where: British Beer Company, 263 Grand Avenue, Falmouth
The Daniel Byrnes Band brightens your Thursday nights with a unique blend of folk, rock, and soul every week at the Falmouth BBC. Get down tonight!
See more events with tags: daniel byrnes british beer company daniel byrnes quartet


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Full Suspension Mountain Bikes up to 25% off
SPECIAL OFFERFree Spin Doctor Pro Build with Purchase of This Bike See details
SPECIAL OFFERTotally Free Shipping and Assembly When Shipped To Store See details
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Devinci Atlas SL Carbon 29er Mountain Bike - 2013The Devinci Atlas SL Carbon 29er is as good as it gets. It features a full carbon DMC-G proprietary frame with a tapered headtube, bb92, 12x142 rear-axle, and more hi-tech components from leading brands then you may even thought possible.
The Devinci Atlas SL is their premium level, superlight, cross country 29er full suspension bike. It features a featherweight and stiff DMC-G carbon frame with full response geometry and a tapered 1 ¼" headtube. Devinci Carbon Monocoque technology uses multidirectional layers of carbon fiber that are superimposed in a specific pattern. They also use Nano Powder, which is way of reinforcing the resin with microscopic carbon tubes. FRG, or full response geometry, puts riders in the best possible XC position. It gives every ride a quick and aggressive behavior at lower speeds and maintains unparalleled stability at higher speeds. Additionally, low standover height gives the Atlas SL a nimble feel. The Atlas frame also features a BB92 Press-Fit bottom bracket. BB92 offers frame designers a little more room for new designs in seat/down tubes and rear suspension layout. Where a typical mountain bike has a 68mm or 73mm bottom bracket shell width, a BB92 equipped bike has a shell that measures 91.5mm wide.
The Devinci Atlas SL uses Dave Weagle's patented Split-Pivot suspension system, where traction, efficiency, maneuverability, and frame stiffness are important factors on singletrack or wide open trail. Split-Pivot offers true performance advantages over other designs by separating acceleration forces from braking forces. This reduces excess suspension compression due to acceleration forces, and at the same time reduces excess compression due to braking forces. The result is an incredible efficiency of power transmission.
Fox is widely recognized as a leader in fork design and performance. The Atlas SL features the all-new Fox Float 32 CTD FIT 29 Factory Series fork with a gorgeous Kashima coating. While the name is a convoluted mouthful, the design couldn't have been made easier for any rider to use. Forks in general have become over-complicated to tune. Lockout, rebound, preload, both high speed and low speed compression -- it can be overwhelming. The new CTD design (Climb, Trail, Descend) utilizes one lever to quickly switch the compression to the ideal setting. The Climb setting adds low-speed compression to diminish bobbing when standing on the pedals. Trail mode presents moderate low speed compression to balance efficiency and the Descend setting features the ideal blend of high and low speed compression for plush action on steep and aggressive sections of trail.
The Atlas SL drivetrain is powered by SRAM's top of the line XO 10-speed group. The SRAM carbon S2210 crankset has a more forgiving 36/22-tooth ring configuration. Together with the 11/36 cassette, the Atlas SL has great gear development for handling technical, obstacle strewn ascents without sacrificing the gears to get back down quickly. The XO Type 2 rear derailleur features 1:1 actuation for precise shifts and Direct Route Technology routes the cable directly to the actuation mechanism. The result is less friction and consequently less effort. SRAM put a Roller Bearing Clutch in their Type 2 derailleurs. The clutch comes pre-set from the factory to provide a certain amount of friction inside the derailleur cage pivot. This friction keeps the cage from bouncing up and down over rocky trails and de-tensioning the chain. Cage Lock technology allows you, with the push of a button, to lock the derailleur cage in an extended position. This is a nice feature that allows for easier-than-ever rear wheel installation.
Easton EA70 XCT wheels are widely spec'd by many bike brands for their compromise between durability and lightweight performance. While many wheels aspire to provide this balance, they often exceed 2000 grams in weight. Not the EA70 XCT. They weigh only 1745 grams. This UST compatible wheel set features welded Easton aluminum rims, butted spokes, a generous 19-millimeter internal rim width for the incredibly light and supple Schwalbe Racing Ralph 2.25 tires, and sealed cartridge bearings. Finally, the thru-axle 15x100 front and 12x142 rear wheel supply incredible stiffness for maximum power transfer, resulting in a bike that tracks in and out of tight single track corners like it's shot out of a cannon.
The 2013 Devinci Atlas SL Carbon 29er mountain bike is all business. It features industry leading technology and components, tremendous graphics and executed on a lightweight carbon 29er split-pivot platform. Let the bike do the work, you just enjoy the ride.
- Carbon DMC-G 29er frame with split pivot technology, tapered head tube and 12x142 rear thru-axle
- Fox Float 32 CTD FIT 29 Fork with 100mm of travel, Factory tuned with Kashima Coating provides exceptional suspension
- Rock Shox Monarch RT3 with custom tune and rebound control
- SRAM X.O drivetrain including Type 2 rear derailleur with Roller Bearing Clutch
- Avid Elixir 9 hydraulic brakes offer exceptional stopping power
- Easton EA70 XCT wheelset with front and rear thru-axle design
- Supple and tacky Schwalbe Racing Ralph tires
Devinci Atlas SL Carbon 29er Mountain Bike - 2013
- bottom bracket:
- SRAM PressFit BB92
- brakes:
- Avid Elixir 9
- cassette:
- Shimano 10s 11-36T
- chain:
- Shimano 10s
- crankset:
- SRAM Carbon S2210 36/22T
- fork:
- Fox Float 32 CTD FIT 29 100mm, w/Kashima
- frame:
- Carbon DMC-G 29er frame, split pivot technology, tapered head tube, 12x142 rear thru-axle, low stand over height, BB92 standard bottom bracket, FRG adjustable and Axis intelligent link
- front derailleur:
- grips/tape:
- Devinci Performance w/lock-on
- handlebar:
- Easton EC70 carbon Flatbar 31.8mm*685mm
- headset:
- Cane Creek 40-Series Integrated
- levers:
- Avid Elixir 9
- pedals:
- None
- rear derailleur:
- rear shock:
- Rock Shox Monarch RT3
- saddle:
- Selle Italia Q-Bik XC
- seatpost:
- Easton EA70 31.6mm
- shifters:
- stem:
- Easton EA90 31.8mm
- tires:
- Schwalbe Racing Ralph 29x2.25
- wheelset:
- Easton EA70 XCT
- rating:
- 4


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There are six movies that I am really looking forward to that open this weekend, most in limited release. The biggies are Elysium and We're the Millers. The others are I Give it a Year, In a World...., Lovelace and Prince Avalanche.
Elysium is the first big budget movie for writer/director Neill Blomkamp. Blomkamp is best known for the Oscar nominated District 9, which starred his good friend and Elysium cast member, Sharlto Copley. The movie isn't getting rave reviews but it certainly has me excited:
We're the Millers stars Jason Sudeikis and Jennifer Aniston. The trailers and clips that have come out look very funny but a part of me thinks it's going to be one of those comedies that sadly features all the good stuff prior to it's release, then leaves you disappointed. I hope that's not the case because Sudeikis always cracks me up and I would rather not waste my time.
Here are the other wide release movies this weekend:
Percy Jackson: Sea of Monsters
And now some of the limited release movies:
I'm a sucker for a British comedy and I really wish more people would give really inappropriate toasts at weddings.
It's an offbeat, quirky comedy and I can't wait. I really like Paul Rudd and Emile Hirsch. They look like they have great chemistry and comedic timing. Should be a feel good comedy.


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January: BOAC flew its inaugural non-stop London to Miami service.
March: The first BOAC Boeing 747 hangar was completed at Heathrow.
6 March: The first commercial flight of BEA Airtours Limited Gatwick to Palma took place.
April: The first BEA direct scheduled services between London and Inverness and London and Bucharest took place.
1 May: BEA commenced the London to Pisa service.
1 June: The inaugural flight of BEA London to Belgrade and Sofia service by Trident Two aircraft took place.
24 September: HRH Princess Alexandra opened BOAC's new passenger terminal at John F Kennedy International Airport, New York.
7 November: BEA commenced services between London and Marrakech, routing via Gibraltar.
December: British Overseas Air Charter Limited was formed.
1 January: Mr Henry Marking became chairman of BEA and a member of the board of BOAC following the retirement of Sir Anthony Milward on 31 December.
Mr Keith Granville became chairman of BOAC and a member of the Board of BEA, succeeding Sir Charles Hardie.
Mr J Ross Stainton was appointed BOAC Managing Director.
February: The first of 26 Trident Three aircraft was accepted by BEA.
March: BOAC's West African routes and London to Tripoli route were transferred to British Caledonian Airways.
1 March: The first revenue earning flight of a BEA Trident Three aircraft (G-AWZB) from London to Paris Orly Airport took place.
14 April: BOAC operated its first commercial Boeing 747 flight, flying from London to New York (JFK) on G-AWNF.
April: A major reorganisation of the BEA Group structure became effective. The group was split into ten separate operating units.
2 April: BEA commenced services from London to a variety of destinations; Zagreb, Reykjavik and Heraklion (Crete) .
2 May: BEA commenced services from London to Leningrad.
July: BEA's new £1.3 million Engineering Training and Computer Centre building was completed.
September: The new BEA £2.6m large hangar for future wide-bodied aircraft was handed over to the airline.
7 October: Mr David Nicholson was named as the first chairman of the British Airways Board.
31 October: After more than 25 years, BEA ceased operations into Paris Le Bourget Airport.
1 November: A new Birmingham to Malta Trident Three service was introduced. New BEA services commenced from London to Rhodes, and also commence non-stop flights from London to Istanbul
27 January: FICO (Flight Information and Control of Operations), the real-time computer control of day-to-day flight operations, was launched.
1 April: The Queen's Award for Industry was conferred upon the Management Services Department of BOAC for technological innovation in respect of the BOADICEA real-time computer system.
New BEA services commenced from London to both Tangier (via Malta) and Marseille, and also from Manchester to both Geneva and Munich.
May: New BEA services from London to Cagliari (Sardinia), and from Jersey to Amsterdam commenced.
Following the recommendation of The Edwards Committee, the government announced its intention to merge BEA and BOAC to form British Airways.
1 September: The British Airways Group was established, which would eventually result in BOAC and BEA being dissolved on 31 March 1974 upon the formation of British Airways.
31 March: BOAC and BEA were dissolved following the formation of British Airways the previous year.
Two British Aerospace 748s were ordered shortly after the merger, with delivery scheduled for 1975 for use in Scotland, where they would begin to replace the ageing Viscount and also support North Sea exploration.
The Standard VC-10 fleet and three remaining Vanguards were retired due to over capacity.
October: The first Lockheed Tristar arrived in October, but did not enter service until January 1975 because of industrial problems.
January: British Airways introduced Lockheed Tristars on European routes, initially to Brussels, Madrid, Malaga, Palma and Paris Charles de Gaulle.
12 January: British Airways launched the British Airways Shuttle, Europe's first walk on, no-reservation, guaranteed seat service from Heathrow to Glasgow.
May: An agreement with Air New Zealand (ANZ) enabled ANZ's DC-10 aircraft to be flown by BA crew for use on the Heathrow to Los Angeles route, in place of BA's Boeing 707 aircraft.
13 Viscounts were withdrawn during 1975 to 1976 to reduce some of regional division's losses.
The Rolls Royce-powered Boeing 747-200 aircraft was launched after British Airways placed an order for four aircraft.
21 January: The world's first passenger supersonic services were inaugurated simultaneously by British Airways to Bahrain (Concorde G-BOAA) and Air France to Rio de Janeiro via Dakar.
24 May: Concorde flights to Washington Dulles commenced, but problems with noise levels delayed operations to New York's JFK airport.
June: BA's first two Boeing 747-236s were delivered.
April: A major reorganisation saw the airline adopt a single functional-based operating structure with departments set up to oversee Flight operations, Engineering and Planning for the whole airline. Commercial operations were split into geographical route groups: UK& Ireland, North and East Europe, West and Southern Europe, and for the longhaul network: Eastern, Southern and Western routes.
The search for new shorthaul airliners to replace Tridents began.
2 November: HM The Queen flew from Barbados to Heathrow on Concorde G-BOAE at the end of her Caribbean tour.
22 November: Concorde services finally started to New York JFK and then on 9 December to Singapore. The Singapore operation was an extension of the Bahrain service and was operated in conjunction with Singapore Airlines. Concorde G-BOAD wore Singapore Airlines' livery on its port side with the BA livery on the starboard side for use on that route.
July: Orders for 19 Boeing 737-236 and three BAE 1-11 539 aircraft were placed.
January: Two Lockheed Tristar – 200 aircraft were ordered, followed by six in September, which was BA's final Tristar order. Deliveries took place between March 1980 and May 1981.
Concorde began operating between Washington and Dallas under a lease agreement with Braniff International in January. Three services per week operated until June 1980.
March: The new Boeing 757 aircraft was launched with orders for 19 from British Airways and 21 from Eastern (USA).
May: The first of six long-range Tristar – 500 aircraft entered service between London and Abu Dhabi.
A Conservative government was elected which declared that BA would no longer receive any state support or interference in its commercial decision making.
July: The government's intention to go ahead with privatisation was announced but this was soon delayed by a forthcoming recession which plunged BA into massive losses.


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Dateline Duluth, Minnesota.
This just in.....I'm an idiot!!!
OK, maybe not quite an idiot; but my fiance' and I are starting to prep for our second 5K run of our lives. Without very much training and no experience, we competed the William A. Irvin 5K back in June by running the distance in 39:12. Not bad for a first effort.
Now that we're both a little wiser, I'm expecting a better time and fewer aches and pains once we complete the Harvest 5K with Essentia Health in October. Here's how:
-Hydrate!! I drank water that day, but needed more. I have a Personal Trainer friend who says one should really start hydrating 36 - 48 hours prior to the race. That way your body has enough fluids - without running with a gut full of water.
-Water As tempting as Gatorade and Powerade can be....resist. Just remember; your body is comprised mostly of water - not Gatorade. Hydrate with what you're going to be losing.
-RUN Before our first 5K I ran.....kinda. Now I am planning on running at least a mile every chance I get, with a two - three mile run once a week. This way I'm building stamina without burning myself out. I will continue this until about 5 days before the race - than I'll taper off to reserve energy.
Carbs In/Protein Out For 24 hours prior to the race, I will increase my intake of Carbs. Carbohydrates are what you body turns into Sugar which it burns for energy - ensuring I don't run out of gas during the run.
Post race I'll have both a Protein Shake and Protein Bar ready to help recovery of muscles that get shredded by running such a distance.
Set A Goal We ran 5K in 39:12 back in June. The goal is to hit 5K in 33:00 or less this time.


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Small pale blue 'Aster' sofa bed with dark wood feet
Item No.3220015380
This small sofa bed from the 'Aster' range is finished in pale blue fabric with neat, dark wood block feet. It features removable cushions and can be easily converted into a comfortable bed, making it ideal for smaller spaces.
- This item can be delivered to UK mainland, ROI and NI addresses only (i.e. delivery not available to Isle of Man, Channel Islands, & Scottish Isles)
- Removable and reversible seat and back cushions help to equalise wear
- Care instructions: Vacuum carefully to remove dust and blot spills with a clean, damp cloth. Plump cushions regularly to help retain their shape
- Dimensions (HWD): 94 x 189 x 96cm
- Seat depth: 50cm
- Arm height: 70cm
- Mattress dimensions (HWD): 183 x 113 x 10cm
- Soft polyester and acrylic mix fabric
- Dark wood feet
- Warranty: 1 year
- Delivered to room of choice, unwrapped and assembled (where product requires assembly) and packaging removed
Debenhams is happy to exchange or refund your purchase within 28 days providing the goods are in a fully resaleable condition (including tags) and not within the exclusion policy*. This policy does not affect your statutory rights. You can return unwanted items either by visiting your local store (the fastest way to get a refund), by arranging a courier collection or returning by post. Exclusions apply to selected products. For instructions on how to return products and information on Debenhams refund policy visit the returns and refunds section of the website.


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This page contains Cheats for Empire Manager HD organized by sections for IPad. Empire Manager HD is a Action General game, made by Eccentricity, released on Jul 30, 2014 and published by Eccentricity. If you can't find a hint or secret in our list, then please check this page periodically for the latest updates. Note: This apple iPad game app may also be compatible with the game app for apple iPhone.
- Developer:
Empire Manager HD IPad CheatsEccentricity
- Publisher: Eccentricity
- Genre: Action General
- Release Date: Jul 30, 2014
- ESRB: Not Set
Stuck on this game? Set a specific, clearly defined question and let others answer your question or view answers to previously asked questions. If you think you are an Empire Manager HD expert then please try to help others with their questions.
Don't forget to Bookmark this page for the latest Empire Manager HD Cheats. At this moment there are no cheats or walkthroughs available for Empire Manager HD. If you know cheats, secrets, hints or glitches for this game then please Submit them.
Left In The Dark: No One On Board HD - Gameplay Review Trailer
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The Cursed Ship, Collector's Edition HD - Gameplay Trailer
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Mystery Of The Opera HD - Trailer
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- Kim Kardashian: Hollywood - Gameplay, (Iphone-Ipod)
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- How To Train Your Dragon 2 - Ready To Fly Trailer, (Wii)
- The Settlers - Kingdoms Of Anteria - Announcement Trailer, (PC)
- Entwined - Quick Look Trailer, (PS3)
- Blue Estate - Official Launch Trailer, (PS4)
- Goat Commando 3D Simulator - Gameplay, (Iphone-Ipod)
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The voice of energy efficiency.
And one of the very few places
you can find David Cameron's
energy efficiency speech.
RT @RegenSW: Industry needs a stronger voice in Westminster to get good policy @EnergySvgTrust @uk_ace - @EnergyBillRev is one such movemen…
RT @RegenSW: Industry needs a stronger voice in Westminster to get good policy @EnergySvgTrust @uk_ace - @EnergyBillRev is one such movemen…
RT @RegenSW: Industry needs a stronger voice in Westminster to get good policy @EnergySvgTrust @uk_ace - @EnergyBillRev is one such movemen…
RT @RegenSW: Industry needs a stronger voice in Westminster to get good policy @EnergySvgTrust @uk_ace - @EnergyBillRev is one such movemen…
ACE welcomes Shadow Secretary for Energy and Climate, Caroline Flint's pledge at the Labour party conference today to 'make energy saving a national infrastructure priority'. We also welcome the commitment to require private rented accommodation to meet a decency standard by 2027: we urge the Labour party to ensure that this standard is set high enough (EPC band C) to deliver homes that are fit for purpose in a low energy, low carbon economy. Delivering on the infrastructure priority promise requires investment: why then are Labour confining themselves only to a level of action that can be achieved 'without spending any more money'?
ACE has today issued this statement on the overnight closure of the Green Deal Home Improvement Fund. Jenny Holland, Head of ACE's Parliamentary Team, said: "The runaway success of the Green Deal Home Improvement Fund shows that there is no shortage of householder demand for energy efficiency improvements. However, in the wake of the decimation of ECO and the failure of the Green Deal to generate significant take-up, the last thing the energy efficiency industry needs is this kind of stop-start programme. "As recently as Tuesday DECC announced that they were cutting the cashback for solid wall insulation from £6,000 to £4,000. Three days later – and with no warning – the scheme has been closed completely. This is bad news for an industry that is looking for policy certainty and consistency – not a relentless pattern of peaks and troughs in demand. "To create industry confidence we need long-term policies and programmes that are not chopped and changed from one day to the next. Structural incentives like stamp duty and council tax incentives will help create the certainty for which industry is crying out." For more information, contact: Jenny Holland, email@example.com, 07875 629781
ACE Research and the Energy Bill Revolution have prepared a high-level briefing outlining the flaws of DECC's draft fuel poverty strategy for England and setting out what the objectives of the fuel poverty should be. This is especially recommended reading if you are in the process of responding to DECC's fuel poverty consultation, which closes on October 7.
Bosch Thermotechnology Ltd. is the UK operation of the Bosch group's heating and hot water division, manufacturing condensing boilers as well as solar water heaters and ground source heat pumps. Part of the Bosch Group, our products are designed, manufactured, sold and distributed with the quality and reliability that is synonymous with the Bosch name.
InstaGroup was founded in 1980 in response to an increasing public awareness of the need to conserve heat and energy, both to protect the environment and reduce consumption of the world's resources.
Celotex is the UK's leading manufacturer of high performance PIR thermal insulation boards. As such, when you choose Celotex insulation, you are accessing an unrivalled product and service package that has evolved through a process of constant innovation spanning eight decades.
The evolution continues with intensive product development to ensure that our product range provides thermal insulation solutions that meet the requirements of current legislation as well as the demands of building professionals, specifiers and users. All of the company's products are manufactured at its plant and HQ in Suffolk.
With over 490 branches nationwide, Plumb Center is one of the UK's leading suppliers of plumbing and heating products including central heating systems, bathrooms, showers, drainage and renewable technologies. It has developed training centres in Leamington Spa and Sevenoaks where around 13 renewable products courses are on offer, and has 38 commercial Centers of Excellence located in carefully selected branches across the UK.
The Vaillant Group is an international family-owned company with more than 135 years experience in the heating and hot water technologies industry. As one of the world's market and technology leaders, the company develops and produces tailor-made products, systems and services for heating, cooling and hot water, and is the one of the largest European manufacturers within the sector.
The Vaillant Group is established and active with production and research and development sites in over 20 countries worldwide. As the UK's number 1 heating manufacturing group, Vaillant Group's UK operations include the market leading brands Vaillant, Glow-worm and Heatline.
Carillion Energy Services (CES) is one of the UK's largest independent energy services providers and a major installer of renewable technologies. Through its activities across a range of markets, including social housing, commercial and non domestic property, and private housing, CES is focused on helping customers reduce their energy costs and make carbon savings.
CES is part of Carillion Plc, which has more than 50,000 employees operating in support services, Public Private Partnership projects, and offering construction capabilities in the UK, Canada and the Middle East.
As the world's leading manufacturer and innovator in mineral wool insulation, ISOVER aims to create safe, efficient and environmentally positive thermal, acoustic and fire safe solutions for customers and end users.
For over 40 years, ISOVER has pioneered and perfected the technologies that have set new standards in the building industry.
Kingspan Insulation specialise in the solution of insulation problems and offer the widest range of insulants available from any UK or Irish manufacturer. Kingspan Insulation is a member company of the Kingspan Group plc, one of Europe's fastest growing building product groups.
Knauf Insulation is UK's leading insulation company. It represents one of the most respected and progressive names in European building products. Knauf Insulation is the only UK manufacturer of glass mineral wool, rock mineral wool and extruded polystyrene insulation products, giving an unrivalled range for building, H&V, process and appliance insulation, as well as fabrication applications.
Superglass Insulation Ltd., which has 211 employees, began operations at its Stirling site in 1987 and quickly established itself as one of the UK's leading manufacturers of insulation products. Superglass offer a comprehensive range of products, which are certified for use throughout Europe. They are manufactured from glass fibre mineral wool and are designed to provide high quality thermal and acoustic insulation.
Honeywell are the leading suppliers of domestic heating and combustion controls in the UK with products that include time, temperature, gas and water controls, designed to provide the homeowner with the best in comfort, energy and health solutions.
Dow is a diversified chemical company that harnesses the power of science and technology to improve living daily. The Company offers a broad range of innovative products and services to customers in more than 175 countries, helping them to provide everything from pharmaceuticals to paints, packaging and personal care products.
CIGA is an independent agency with its own secretariat that provides independent 25 year Guarantee covering cavity wall insulation. It is governed by a council of "System Designers" (who supply the insulation material) and registered installers, with support from trade associations and Government bodies.
Sheffield Insulations has 50 years experience in insulation distribution. As part of the SIG plc Group, we supply materials for thermal and acoustic, dry lining, fire protection and house building.
We offer more than 50,000 brand name products from leading manufacturers with rapid responses to customers enquiries via our 20+ branch network.
Rockwool Ltd, based near Bridgend, South Wales is the UK's leading manufacturer of mineral wool insulation for thermal, fire and acoustic protection. Only Rockwool is authentic and wholly natural, recreated from natural processes that exist only in nature.
Mark Group began insulating homes back in 1974 and recognised that this is the first step in helping save energy, money and carbon emissions. Today, Mark help make over 3,000 homes more energy efficient every week, from their 14 regional locations.
Their services are tailored for individual homeowners as well as builders, architects, local authorities and government bodies.


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A small dog was taken from a woman's car on Sunday. Now a woman says she wasn't trying to steal the dog. She was trying to save its life because it was locked in a car on a hot day. However, the dog's caregiver isn't so sure.There was a happy reunion Monday at the Wyandotte pound. Five-month-old Coco is back with her family.Alana Freeman and her family went shopping in Allen Park and left Coco in the car in her carrier. When they came out, she was gone.A woman, who asked us not to identify her, said Coco got her attention."I heard a dog barking like crazy, like going crazy, like super high pitched," she said. "It was like a two pound dog that was in a carrier. It couldn't get to the air."The self-proclaimed dog lover said she and her husband tried to find the owner. When that didn't work, she said she called the police."We waited and waited and waited, and I waited by the car, and he was walking up and down the street asking people if that was their car," she explained.She said police never arrived."When I went back, I could see through the mesh in the carrier, and the dog was on its side, and it was up and down really fast, its chest or like its belly, and its tongue was hanging out of the side of its mouth," she claimed.That is when she made her move."All I did was just stuck my hand in the window and opened the door," she explained.She said she waited even longer, and then left with Coco an hour-and-a-half after she found her."It's not like I wanted to take the dog from her owner. I didn't want the dog to die," she remarked."I'm sure she's not a veterinarian or anything like that, so how valid is her opinions?" Freeman said. "All four windows were down... and I wasn't in the store that long, and my air conditioner was running.""On a 78 degree day, it can reach 100 degrees in 20 minutes. So I knew it was somewhere around 80 degrees," the dog lover said. "Don't leave your dogs in the car. They will die fast.""It comes up on the news with the reward, and now you're saying my dog was in that condition. I mean, that's hard to believe," Freeman said.We asked Animal Control what should someone do if they find themselves in this situation. They told us the best thing to do is not to pop the lock and take the dog, but to call police. Don't get involved. Wait for someone to come and release the dog.
25 FOX DriveDedham, MA 02026
Phone (781) 467-2525


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Amarillo, Texas - The convenience of straight-ticket voting could one day no longer be an option in Texas. Three Texas politicians are seeking to end or limit straight-ticket voting. Texas is one of only 14 states that still allow it.
"There's two bills out there. One that would completely take away the straight-party voting, the other would take away the straight-party voting in local offices," Knoxie Mathes, Potter County Election Administrator says.
We asked how this would effect voters in our area. The number of panhandle residents who utilize straight-ticket voting is high. More than half of voters in Randall County used this option during November's election. Even more people voted this way in Potter County.
"In the 2012 general election we had maybe about 15 to 16 thousand that vote straight party out of 26 thousand that actually voted," Mathes says.
Straight-ticket has been a way to make time spent at the polls short and easy. But with this legislation, that could change and add confusion for voters, especially if limiting straight voting.
"Because of the fact they would think that they are voting straight party it would cover everybody on the ballot. There would be a lot of instructions involved, and so that would be a little bit harder on the voter than to have total straight party taken off of the ballot," Mathes says.
Representative Dan Branch from Dallas whose proposal eliminates straight-ticket says the most important base unit of democracy needs to be protected from coercion and laziness.
Republican Party of Potter County chairman, Tonya Denton, says although she agrees voters should be educated on candidates, she is a supporter of keeping straight-ticket voting. Over on the democratic side, the feelings were mutual.
"People don't like change. It will discourage some people. They want to go up there and vote and get through with it. Just like when the new voting machines came out, some people didn't go vote because they didn't want to get embarrassed," Gentry Powell, Democratic Party of Potter County Chairman says.
These proposal are still currently seeking state legislature approval.
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