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Gene Variant May Identify Cirrhosis Patients at High Risk of Liver Cancer
Researchers from Massachusetts General Hospital have found that a single nucleotide polymorphism (SNP) - a change in a single unit of DNA - in the epidermal growth factor (EGF) gene may significantly increase the likelihood that a patient with cirrhosis will develop hepatocellular carcinoma (HCC).
HCC is difficult to treat and most commonly arises in patients with cirrhosis, often caused by chronic infection with the hepatitis B or C viruses. The results of this study, published in the January 2 Journal of the American Medical Association, may help identify a subset of patients who would benefit from intensified screening and possibly chemoprevention strategies. Read more
Sunitinib Linked to Heart Failure and Hypertension
Patients taking sunitinib (Sutent) should be monitored for cardiovascular side effects such as hypertension and signs of heart failure, especially those patients with a history of coronary artery disease or cardiac risk factors, a team of oncologists and cardiologists said last month in The Lancet. The recommendation is based on evidence of cardiac side effects among some patients taking sunitinib to treat gastrointestinal stromal tumors (GIST). Sunitinib is approved to treat advanced renal cell carcinoma and metastatic GIST after resistance to imatinib (Gleevec) develops.
Dr. Ming Hui Chen of Harvard Medical School and her colleagues retrospectively analyzed the medical records of 75 GIST patients treated at the Dana-Farber Cancer Institute during a phase I/II study. A total of 11 percent of patients had a cardiovascular event - two patients had heart attacks and six others experienced heart failure. In addition, 47 percent of patients developed hypertension - systolic and diastolic blood pressure increased during the first cycle of treatment - and 20 percent had reduced heart function. Read more
Gene Variant May Identify Cirrhosis Patients at High Risk of Liver Cancer
Researchers from Massachusetts General Hospital have found that a single nucleotide polymorphism (SNP) - a change in a single unit of DNA - in the epidermal growth factor (EGF) gene may significantly increase the likelihood that a patient with cirrhosis will develop hepatocellular carcinoma (HCC).
HCC is difficult to treat and most commonly arises in patients with cirrhosis, often caused by chronic infection with the hepatitis B or C viruses. The results of this study, published in the January 2 Journal of the American Medical Association, may help identify a subset of patients who would benefit from intensified screening and possibly chemoprevention strategies.
The investigators focused on a SNP in the EGF 61*G allele, in which one or both copies of a specific adenine nucleotide (A) in the EGF gene are replaced with a guanine nucleotide (G). Previous work in both cell cultures and animal models showed that this SNP plays a role in raising EGF protein levels, and EGF has been implicated in liver tumor formation in animals.
"We deliberately chose to focus on one SNP that had previous data suggesting that it's functional" in carcinogenesis, explained Dr. Kenneth Tanabe, lead author of the paper.
The researchers examined DNA from all 207 patients with cirrhosis who had blood or tissue stored in the Massachusetts General Hospital Cancer Center Tumor Bank between 1999 and 2006. Of these patients, 59 developed HCC.
Patients with one copy of the SNP (A/G genotype) were more than two times as likely to develop HCC, and patients with two copies (G/G genotype) were four times as likely to develop the cancer as patients with the A/A genotype. These associations remained significant even after adjusting for age, sex, race, and cause and severity of cirrhosis. The researchers found correspondingly higher EGF and phosphorylated EGF receptor (EGFR) levels in the liver and serum of patients with the G/G genotype.
Collaborators at the Hôpital Paul Brousse in France provided genetic data for a validation study, from 121 white patients with alcoholic cirrhosis seen between 1993 and 2006. Forty-four of those patients later developed HCC.
As in the Massachusetts population, patients with the G/G genotype were significantly more likely to develop HCC - in this case almost three times as likely - than patients with the A/A genotype.
Although "prospective studies examining larger populations of patients…and the application of these observations to ethnic minorities," are needed, explain the authors, they remain intrigued by the possibilities for HCC screening and prevention.
"Identification of molecular markers associated with an increased risk of hepatocellular carcinoma would better define populations at highest risk…and may additionally define important therapeutic targets for prevention and treatment," they state. "Our findings…provide rationale for examination of the EGF-EGF receptor pathway as a novel target for chemoprevention in humans."
Dr. Tanabe's laboratory has begun preliminary work to look for a chemoprevention agent nontoxic enough for long-term use. "We're already looking at the EGF-EGFR pathway using in vitro transformation models to screen potentially clinically useful compounds that would inhibit transformation, and are also developing similar animal models. Setting up those platforms for drug discovery and drug testing could go in parallel with a confirmatory study…It happens to be that a SNP modulates serum EGF levels [in this study], but of course there may be many, many other things that modulate EGF levels," he concluded.
—Sharon Reynolds
Sunitinib Linked to Heart Failure and Hypertension
Patients taking sunitinib (Sutent) should be monitored for cardiovascular side effects such as hypertension and signs of heart failure, especially those patients with a history of coronary artery disease or cardiac risk factors, a team of oncologists and cardiologists said last month in The Lancet. The recommendation is based on evidence of cardiac side effects among some patients taking sunitinib to treat gastrointestinal stromal tumors (GIST). Sunitinib is approved to treat advanced renal cell carcinoma and metastatic GIST after resistance to imatinib (Gleevec) develops.
Dr. Ming Hui Chen of Harvard Medical School and her colleagues retrospectively analyzed the medical records of 75 GIST patients treated at the Dana-Farber Cancer Institute during a phase I/II study. A total of 11 percent of patients had a cardiovascular event - two patients had heart attacks and six others experienced heart failure. In addition, 47 percent of patients developed hypertension - systolic and diastolic blood pressure increased during the first cycle of treatment - and 20 percent had reduced heart function.
Most cardiac problems including hypertension were manageable and the majority of patients with heart failure resumed sunitinib therapy. Histories of coronary artery disease and/or hypertension were predictors of cardiovascular events.
Cardiac side effects have been reported for other successful targeted cancer drugs such as trastuzumab (Herceptin) and bevacizumab (Avastin). The study supports a growing view that oncologists and cardiologists need to work together to identify the cardiac side effects of new, targeted drugs and to manage cardiac health throughout therapy.
"The paradigm remains to treat the cancer while caring for the heart," said Dr. Chen, a cardiologist who specializes in the cardiac health of adult cancer patients. She noted that although the cardiotoxicity in this study was not seen in phase III trials, the patients may be more similar to patients in the general population now being treated with sunitinib.
A letter in the January 3 New England Journal of Medicine reports on 14 patients with metastatic renal cell carcinoma who also experienced rapid, marked increases in blood pressure during treatment with sunitinib. The effect was revealed by home blood-pressure monitoring and had been missed during routine office visits.
"Our study suggests that rapid and large increases in blood pressure should be anticipated in patients who are treated with sunitinib," conclude the authors from Hôpital Européen Georges Pompidou in Paris.
Cancer Doctors May Need Training on Empathy Skills
Cancer specialists (oncologists) may need additional training to encourage patients to express their concerns and negative emotions and to respond empathically to these concerns, researchers recommended in a study published December 20, 2007, in the Journal of Clinical Oncology.
The report presented data from the Studying Communication in Oncologist-Patient Encounters (SCOPE) project, an NCI-funded, three-site study from Duke University, the Durham Veterans Affairs Medical Center, and the University of Pittsburgh. It is based on results from 398 clinic conversations between 51 oncologists and 270 patients with advanced cancer. The study found that the oncologists encountered few empathic opportunities during their patient meetings (37 percent of visits) and responded with empathic statements infrequently (only 22 percent of the time).
Empathic responses are important in cancer care because "patients have less anxiety and depression and report greater satisfaction and adherence to therapy," the researchers noted. The study found that female patients were more likely to disclose painful emotions to female oncologists. In addition, younger oncologists and those who rated their orientation as more socioemotional than technical were more likely to respond with empathic statements.
"Oncologists and patients need to work to create an alliance conducive to patients expressing their emotions," the researchers suggested. Although the oncologists expressed high levels of confidence in addressing emotions, they may need more training to recognize emotions and to learn how to respond to patient concerns. "Many empathic opportunities were indirect and patients may be more satisfied if they can learn how to express their emotions more directly so that oncologists can respond appropriately," the authors noted.
Biomarkers Linked to DCIS Outcomes
Ductal carcinoma in situ (DCIS), where abnormal cells are found in the lining of a breast duct, is usually treated with surgical lumpectomy, followed by radiation, chemotherapy, a combination of the two, or surveillance. Most women undergoing these treatments will not experience a recurrence, but in 15 to 30 percent of women, a new tumor will develop within 10 years, and about half of these will be invasive breast cancers. To help clinicians determine whether DCIS is likely or unlikely to follow this course, researchers at the University of California, San Francisco, and the Bay Area Breast Cancer Specialized Program of Research Excellence (SPORE) have identified biomarkers associated with invasiveness. Their results appear in the November 12, 2007, Cancer Cell.
Using lumpectomy samples from 70 women who were diagnosed with DCIS and then followed for more than 10 years (180 months), the researchers looked at several markers associated with stress-induced senescence or proliferation. They compared the profiles of these markers in women whose DCIS did not progress to those in women for whom the DCIS did progress.
The results showed that in samples containing proliferating cells identified using Ki67 proliferation marker, overexpression of stress-activated p16 and/or COX-2 proteins reflects abnormal response to cellular stress and predicts subsequent tumor events within the first decade after the initial DCIS diagnosis. Low expression of Ki67 (regardless of the p16 and COX-2 status) usually indicates favorable prognosis. Other findings include observation of post-transcriptional rather than transcriptional regulation of COX-2 expression in a subset of HER-2-positive tumors.
The authors conclude that when tissue shows stress activation and deregulation of p16 and Rb signaling, this "may represent a defining signature of basal-like carcinogenesis that can be assayed [before] the development of invasive disease," with opportunities for prevention years before an invasive tumor actually occurs.
Older Breast Cancer Survivors Less Likely to Adhere to Follow-Up
Two new studies have revealed that older breast cancer patients who are more likely to experience recurrence are less likely to undergo recommended follow-up mammography and adhere to prescribed medications. In the clinical trials that lead to treatment and follow-up guidelines for breast cancer, older women are usually underrepresented due to eligibility criteria or comorbid conditions. But two recent community-based studies that focused on breast cancer survivors over the age of 65 addressed specific questions related to the behavior and outcomes of this group, using participants in health systems that collaborate through the NCI-funded HMO Cancer Research Network (CRN).
The first study, published online December 1, 2007, in the Journal of General Internal Medicine, looked at surveillance mammography among women who were diagnosed with stage 2 or earlier breast cancer. Most of the 1,762 women in the study were older than 70. After 4 years of follow-up, the study showed that women at the highest risk of recurrence - those who were diagnosed at stage 2 and those who had breast-conserving surgery without radiation - were the least likely to have recommended mammograms. Other factors associated with this trend included age older than 80 and nonwhite ethnicity.
The second study, published ahead of print in the Journal of Clinical Oncology on December 10, 2007, reviewed tamoxifen use by 961 women during a 5-year follow-up period after treatment. The results showed that 49 percent of these women stopped taking tamoxifen within this time. Women over the age of 75, as well as those who had comorbid conditions, breast-conserving surgery without radiotherapy, and those in whom tumor estrogen-receptor status was unknown, were the most likely to discontinue use. Reasons for stopping in the first year most often related to side effects of the drug.
In both papers, the authors noted that by understanding the risk of nonadherence to recommended follow-up procedures, clinicians may be able to tailor their care of this patient group.
More information on collaborative research opportunities and NCI's CRN resource can be found at http://crn.cancer.gov/about/work.html.
Trial Shows Some Benefit of Adjuvant Chemo for Early Colorectal Cancer
A large European trial designed to determine the value of adjuvant chemotherapy after surgery for stage II colorectal cancer has found that patients receive "small but definite benefit" in both survival and risk of recurrence, say researchers at the University of Birmingham in England.
The QUick And Simple And Reliable (QUASAR) Trial Collaborative Group, led by Dr. Richard Gray, reported results on 3,239 patients after 5.5 years median follow-up in the December 15, 2007, Lancet. Compared with observation alone, patients receiving chemotherapy had an 18-percent reduction in risk of death, which, in a population whose mortality rate is about 20 percent, conferred an absolute reduction of 3.6 percent at 5 years. The 22-percent reduction in risk of recurrence occurred almost completely in the first 2 years, and then leveled off.
"Chemotherapy seems to prevent a proportion of recurrences and deaths rather than just delaying them," wrote the authors, "which makes the life-years gained more substantial, especially for younger patients."
Drs. David Cunningham and Naureen Starling of the Royal Marsden Hospital in Surrey wrote in an editorial that the QUASAR results do not fully resolve all of the issues in this population, and that "identification of patients most likely to benefit from therapy remains important." Subgroup analyses are underway.
Better information about these groups, they wrote, may help patients and physicians assess the risk/benefit ratio among the three options currently in use: fluorouracil with oxaliplatin, fluoropyrimidine, or observation. These newer drugs and combinations have largely supplanted the drugs tested in QUASAR.
Coding Cancer Research Accurately
One of the truly unique aspects of NCI is its close relationship to the cancer community, a relationship made possible by the special authorities granted by the National Cancer Act of 1971. Those authorities include the mandate for robust and frequent communication about the Institute's research priorities and activities, including its support of research grants pertaining to organ sites.
In that light, I wanted to raise awareness about a worrisome new initiative that will change how NIH institutes and centers (ICs) track and report the research they fund. A result of requirements in the NIH Reform Act of 2006, these changes in grant activity reporting are intended to establish stronger, more transparent processes for how all ICs manage their research portfolios through coding of individual awards. It's a laudable objective, but as the old adage says, "The devil is in the details."
In approximately 1 year, NIH plans to roll out the Research, Condition, and Disease Categorization (RCDC) electronic coding system. This system is designed to categorize and catalogue the projects and grants supported by NIH using one central database. The RCDC will include 340 research categories, each with new definitions that will be used to electronically sort ICs' research projects and programs.
In presentations at the most recent meetings of the National Cancer Advisory Board (NCAB) and the NCI Board of Scientific Advisors (BSA), representatives from the NIH Office of Portfolio Analysis and Strategic Initiatives (OPASI) explained how the RCDC will work.
While members of both NCI boards and NCI senior leadership support efforts to create more sophisticated portfolio analysis tools, concerns were raised about whether this new centrally managed coding system could adequately code and track "cancer research." Of particular concern is how basic science will be reported under the RCDC, which as currently formulated, does not adequately capture basic research as a category. Basic discovery is fundamental to understanding the underlying biology of carcinogenesis and tumor progression - and accounts for a substantial cancer research investment that deserves accurate coding and reporting. Complicating basic science reporting further is how to report projects, for example, on signaling pathways that might impact several cancer types. Until questions surrounding coding of basic research are more clearly resolved, there is a real concern that the RCDC could potentially miss, and therefore underreport, NCI's support of basic research.
NCAB and BSA members correctly noted that the complexity of cancer is not easily categorized electronically. NCI has developed a robust system for coding and reporting the research projects it supports, using experienced indexers who ensure that a given project's contributions are adequately captured and reported. This system, which has been refined by NCI over many years, allows dollars attached to each research project to be prorated over specific categories. A real concern by NCI with the proposed RCDC system, which does not prorate projects, is the likelihood of significant misrepresentation of exactly how cancer research dollars are spent. It is difficult to establish an electronic system that can adequately replace expert coders, trained to carefully evaluate each grant, particularly when trying to categorize complex cancer biology research programs.
Board members also voiced their concern that the RCDC cannot account for a large amount of NCI funding that goes to support the extramural cancer research infrastructure, including the NCI-designated Cancer Centers, Cooperative Groups, and NCI's Specialized Programs of Research Excellence (SPOREs).
In short, there is a fear that the RCDC could, in fact, result in a less accurate, less transparent accounting of cancer research support. Finally, the boards felt that the long-standing processes established by NCI for communicating this information to the public, Congress, and the advocacy community would be lost - resulting in confusion and apprehension, especially among the numerous cancer advocacy organizations.
NCI leadership has shared these concerns with OPASI staff and requested that "cancer research" be exempted from the RCDC reporting requirements, as will be done for "AIDS" and "biodefense" research. We are currently working with OPASI leadership to determine if processes can be established so that the coding and categorization that NCI already does can be incorporated into the RCDC system and extended to the proper coding of cancer research across the NIH.
We will keep the community informed of activities and progress in this critically important area. We want to reinforce the importance NCI places on being as open and accountable as possible to the public, as mandated in the National Cancer Act. We firmly believe, however, that this activity must be led by NCI.Dr. John E. Niederhuber
Director, National Cancer Institute
A Kinder Cut: Advances in Surgery for Head and Neck Cancer
Before the development of chemotherapy, radiation therapy, and targeted treatments for cancer, there was surgery. And today, the physical removal of cancerous tissue remains a cornerstone of treatment for most tumor types.
But cutting into the body comes with many risks, and it leaves its mark. In parallel with their colleagues working on the systemic treatment of cancer, academic surgeons have been performing research to improve the outcomes of surgical oncology, attempting to minimize damage, maximize effectiveness, and improve reconstruction of damaged tissue.
Smaller Surgeries
For example, for tumors at the base of the skull, "Traditionally…they would have to open up the face and even maybe remove part of the face to get at these tumors, or come in from above, opening up the skull and moving the brain aside," explains Dr. Carter Van Waes, chief of the Head and Neck Surgery Branch at the National Institute on Deafness and Other Communication Disorders. "It was successful in curing many patients or…palliating the disease, but the functional and aesthetic outcomes were short of what people desired."
The next surgical revolution came in the 1980s and 90s, with the rise of minimally invasive endoscopy applied to head and neck surgery. The endoscope allows surgeons to operate through existing openings, such as the nose and mouth, or through relatively small incisions, potentially reducing surgical morbidity.
Recently, the Southwest Oncology Group tested endoscopic transoral (through the mouth) surgery in a phase II clinical trial for patients with early-stage laryngeal cancer. Although the trial did not have a standard, open-surgery control group, says senior study investigator Dr. David Schuller from Ohio State University, "Subjectively we're seeing absolutely no difference in terms of survival outcomes, but certainly are impressed with the decreased morbidity, the decreased length of hospital stay, and the decrease of blood loss. So we're cautiously optimistic.
"If we could continue to use surgical modalities to help us with cytoreduction at the same time that we decrease morbidity - enabling the patients to move on quickly to nonsurgical adjuvant therapies - that's the hope," he continues. Investigators are now experimenting with robotics-assisted endoscopic surgery in the head and neck region, to assess its feasibility and potentially increased surgical precision in small physiologic spaces.
Putting the Pieces Back Together
Fortunately, reconstructive surgery for the head and neck region has also made great strides in the past 20 years. Before modern tissue transfer techniques became possible, simple skin and nonvascular bone grafts were used to close a remaining defect and prevent infection. But these techniques were not adequate to restore normal appearance, and in the case of bone grafts, were often reabsorbed by the body.
An important advance in surgical reconstruction came with the development of pedicled (attached) regional flap transfer, which allowed surgeons to cut a piece of tissue from a nearby structure (such as a chest muscle) and move it, still attached to its blood supply, to the site of the surgical defect.
Though a vast improvement over nonvascular grafts, this technique was limited to nearby donor tissue. Additionally, the flaps could have problems healing, particularly from tension caused by the attachment to the donor site or damage to the recipient site from radiation therapy. These problems were addressed by the development of free tissue transfer, in which microvascular surgeons remove a piece of muscle, bone, or both, from elsewhere in the body, along with the associated blood vessels, and reattach those blood vessels at the transplant site.
"More and more head and neck surgeons have become trained in microvascular techniques, and I think, once a critical mass of microvascular surgeons was available to perform these procedures and analyze the effect of these reconstructions - showing their superiority in many instances - that really allowed it to become standard [care]," explains Dr. Theodoros Teknos, chief of Head and Neck Oncologic Surgery at the University of Michigan.
Free-flap transfer can also be combined with dental and facial prosthetics, to include artificial ears, eyes, teeth, or other body parts and provide a more natural appearance for patients.
Looking to the future, says Dr. Teknos, "The next big phase in reconstruction is going to be tissue engineering." To avoid the donor-site damage that can be caused by harvesting muscle or bone for free-flap transfer, and to provide more personalized reconstructions, investigators are experimenting with growing custom bone, using adult stem cells, or protein or gene therapy.
Recently, investigators in Germany succeeded in growing a new jaw bone for a man who had undergone an extensive tumor surgery. The researchers filled a custom mesh cage with bone mineral blocks, bone marrow containing hematopoietic stem cells, and bone morphogenic protein and implanted it into the patient's back muscle, creating a new piece of custom-fitted bone with a healthy blood supply that they successfully transferred to the jaw.
For both future ablative and reconstructive advances, participation from all the associated specialties will remain essential. "Bringing together the thought leaders from all over the country, from all of the disciplines…not just the therapeutic, but also the rehabilitative and the quality-of-life expertise…I think that's what's going to accelerate the productivity in clinical research," concludes Dr. Schuller.
—Sharon Reynolds
Genome Scans for Cancer: What's Next?
Scanning the human genome for genetic variants involved in common cancers began to pay dividends in 2007, and the trend is likely to continue as more large studies involving new types of cancer report their results in the coming year.
For the first time, researchers have been discovering and validating genetic variants associated with common cancers such as breast, colon, and prostate. The genetics of these diseases have been exceedingly difficult to dissect, but that is starting to change, thanks to new technologies and the use of large and carefully selected patient populations.
"We're starting to unlock the genetic secrets of common, complex diseases," said Dr. Teri Manolio of the National Human Genome Research Institute, who organized a seminar on genome-wide association studies last summer. "The big lesson in cancer is that you find strong signals in parts of the genome where there aren't any known genes."
Indeed, much of the excitement surrounding genome scans comes from discoveries in places where no one had thought to look, such as a region of chromosome 8 called 8q24. The region has no known genes. But when three prostate-cancer scans published on the same day last year pointed to 8q24, it became a research priority almost overnight.
"The current excitement in the field is about what the scans will tell us about the biology of cancer," said Dr. Thomas Sellers of the Moffitt Cancer Center, who is collaborating on genome scans for ovarian cancer. "It's hard for patients to get excited about that, but this is important for progress in research and developing treatments."
Scans are underway, for instance, to find variants underlying individual differences in cancer risk, drug response, the risk of relapse, and second cancers. And as technology improves and the basic strategy is refined, scans will likely be used in new ways.
In addition to breast, colon, and prostate cancers, scans were reported last year for acute lymphoblastic leukemia. The studies largely involved patients of European descent and will need to be repeated in African and Asian populations. Scans are underway or nearing completion for lung, pancreatic, ovarian, and bladder cancers, to name a few.
A substantial number of these studies will be published for additional types of cancers in 2008, predicted Dr. David Hunter of the Harvard School of Public Health and a leader of NCI's Cancer Genetic Markers of Susceptibility (CGEMS) program. "One can expect that new, previously undiscovered associations will be found, and that should help us learn more about the inherited causes of these cancers."
For prostate, colon, and breast cancers, the story is far from over. Researchers are racing to explain associations among all three cancers and 8q24. The region may contain DNA sequences that regulate cancer-related genes, but further evidence explaining the plausibility of the findings has yet to be published.
"Something mysterious is going on in 8q24, and we are having difficulty putting the data in a rational context," said Dr. Kari Stefansson of deCODE Genetics, which first linked the region to prostate cancer in 2006. Nonetheless, he expects an answer by spring.
"Genome scans are the best tool we've ever had to pinpoint the genetic causes of disease," Dr. Stefansson added. "Never in history have we had anything that comes close. They are not perfect, but the ability to look at hundreds of thousands if not millions of variable regions of the genome at the same time is remarkable."
Scans often involve thousands of subjects. Success depends in part on having relatively homogeneous patient populations and matched comparison groups. DNA from both groups is screened for variants found more often in the affected group. Results are then tested in additional patient populations to confirm associations and avoid false-positives.
Most of the variants reported to date have modest effects on disease risk and would not be used in the clinic. With the next generation of genome scans, researchers will begin to focus on assembling panels of common risk variants.
"The goal is to quickly transition from discoveries in single studies to discoveries in several studies, and to put together strong robust findings so that researchers can test 10 to 20 common variants," said Dr. Stephen Chanock, of NCI's Division of Cancer Epidemiology and Genetics (DCEG), who directs its Laboratory of Translational Genomics.
"We are most excited about the opportunity to put them all together because we know that is where we want to be," said Dr. Chanock. Collaborative studies across the globe will be needed to achieve this goal, and efforts toward this end are underway.
By combining scans for the same cancers, it should be possible to look at subtypes of disease to see if there are specific genetic factors that one wouldn't see when looking at the total group, said Dr. Robert Hoover, also of DCEG and a leader of CGEMS.
Meanwhile, researchers are testing associations in their own study populations. Of particular interest is the increased risk of prostate cancer in African American men. "The initial scans were largely done in white populations, and we're trying to see whether the effects are the same in men of African descent," said Dr. Timothy Rebbeck of the University of Pennsylvania.
Another application is to use scans to find protective genes. One such variant has been found for breast cancer, and others may follow. An international consortium is planning to screen women with mutations in the BRCA2 gene for genetic variants that may cause some of these women to develop breast cancer at an early age and others not.
"If we find a genomic pattern that is protective in the genetic background of BRCA2 mutations then we will see if this result is generalizable," said Dr. Kenneth Offit of Memorial Sloan-Kettering Cancer Center, who is leading a study by CIMBA (Consortium of Investigators of Modifiers of BRCA1 and BRCA2).
Genome scans may indirectly lead to environmental factors involved in cancer. For instance, genes that are more strongly associated with breast cancer in women who use hormones than in nonhormone users may mediate the effects of exposure to hormones. Understanding the biological pathways involved could lead to safer uses of the therapy.
Epigenetic changes to DNA, which regulate gene activity without altering DNA sequence, also play a role in cancer. Understanding the interactions among genetic, environmental, and epigenetic factors on cancer represents an enormous challenge, and researchers stress that genome scans are merely the beginning.
In fact, genome scans often do not reveal the precise stretch of DNA responsible for an association, so more work is needed to pinpoint it. Then, functional studies are needed to truly understand the source of the association.
"Results of scans should be replicated many times by multiple groups before reaching firm conclusions or changing therapy based on the findings," cautioned Dr. William Evans of St. Jude Children's Research Hospital, who has collaborated on leukemia scans and used this approach in pharmacogenomic studies.
Dr. Mary Relling, also at St. Jude, added: "We need to be honest with the public and with our funding agencies that this process is going to be hard and will be done over decades." Nonetheless, she is optimistic and believes that genome-wide approaches are important because they may reveal factors that might otherwise be missed.
Dr. Relling is using scans in combination with other tools to study variation in drug response and toxicities among children with leukemia. And in the field of pharmacogenomics generally, many scans are underway using patient cells.
"Just as the use of scans for identifying risk factors in common diseases has exploded on the scene, you're going to see an echo of that explosion in research on variation in drug response," said Dr. Richard M. Weinshilboum of the Mayo Clinic, a former chair of the Pharmacogenetics Research Network. "Tune in next year for the results."
Researchers have seen "the first light of genetic variants associated with common diseases that we had never thought of before," said NCI's Dr. Chanock, who is a leader of CGEMS. "The excitement comes from seeing that our strategy works and that the approach is sound." The information from these studies will be used in many ways, including some that are not yet apparent.
"We are putting the CGEMS results out there and counting on people to look at the information from many different perspectives," Dr. Chanock said.
—Edward R. Winstead
Stress Management Therapy for Chemotherapy Patients
Name of the Trial
Principal Investigators
Why This Trial Is Important
In this study, patients with newly diagnosed cancer who are scheduled to undergo chemotherapy will be randomly assigned to one of two groups. One group will receive standard psychosocial care along with stress management training, while the other will receive standard psychosocial care alone. The self-administered training will consist of multimedia information and instructions about three stress management techniques: progressive muscle relaxation and guided imagery, abdominal breathing, and coping skills.
Hispanic/Latino patients reportedly experience a disproportionately higher level of suffering from cancer and treatment-related stress. This is due, in part, to a lack of culturally relevant resources in Spanish. This study uses culturally sensitive self-education tools in both English and Spanish that are linguistically appropriate and incorporate Hispanic/Latino cultural beliefs.
"The adverse effects of chemotherapy on quality of life are well documented," said Dr. Taylor. "Stress management techniques have been shown to have beneficial effects on nausea, vomiting, and emotional distress before the administration of chemotherapy as well as in the days following chemotherapy.
"The primary objective of this study is to determine whether a self-administered stress management intervention, previously found to be beneficial to primarily non-Hispanic chemotherapy patients in a single clinical setting, is effective in improving quality of life and decreasing psychological distress (anxiety and depression) in Hispanic and non-Hispanic patients receiving cancer chemotherapy in multiple community clinical settings. We have met our accrual target for non-Hispanics, so the trial is now open only to Hispanic patients," Dr. Taylor added.
For More Information
An archive of "Featured Clinical Trial" columns is available at http://www.cancer.gov/clinicaltrials/ft-all-featured-trials.
Following are newly released NCI research funding opportunities:
Developmental Pharmacology
Letter of Intent Receipt Dates: April 22, Aug. 22, and Dec. 21, 2008; April 21, Aug. 21, and Dec. 21, 2009; April 23, 2010.
This funding opportunity will use the R01 award mechanism. For more information, see http://cri.nci.nih.gov/4abst.cfm?initiativeparfa_id=3827. Inquiries: Dr. William C. Timmer - firstname.lastname@example.com
NIDA Research "Center of Excellence" Grant Program
Letter of Intent Receipt Dates: Jan. 28, 2008; Jan. 26, 2009; Jan. 26, 2010.
This funding opportunity will use the P50 award mechanism. For more information, see http://cri.nci.nih.gov/4abst.cfm?initiativeparfa_id=3826.
Limited Competition: Adult Brain Tumor Clinical Trials Consortium
Letter of Intent Receipt Dates: Jan. 29, 2008.
This is a renewal of RFA-CA-04-001 and will use the U01 award mechanism. For more information, see http://cri.nci.nih.gov/4abst.cfm?initiativeparfa_id=3828. Inquiries: Dr. Jeffrey Abrams - email@example.com
Nanoscience and Nanotechnology in Biology and Medicine
Application Receipt Dates: Non-AIDS Applications (new): Feb. 5, June 5, and Oct. 5, 2008; Feb. 5, June 5, and Oct. 5, 2009; Feb. 5, June 5, and Oct. 5, 2010.
This is a renewal of PAR-07-270 and will use the R01 award mechanism. For more information, see http://cri.nci.nih.gov/4abst.cfm?initiativeparfa_id=3820. Inquiries: Dr. Piotr Grodzinski - firstname.lastname@example.com
Nanoscience and Nanotechnology in Biology and Medicine
Application Receipt Dates: Non-AIDS Applications (new): Feb. 16, June 16, and Oct. 16, 2008; Feb. 16, June 16, and Oct. 16, 2009; Feb. 16, June 16, and Oct. 16, 2010.
This is a renewal of PAR-07-271 and will use the R21 award mechanism. For more information, see http://cri.nci.nih.gov/4abst.cfm?initiativeparfa_id=3820. Inquiries: Dr. Piotr Grodzinski - email@example.com
NCI Transition Career Development Award to Promote Diversity
Application Receipt Dates: Non-AIDS Applications (new): Feb. 12, June 12, and Oct. 12, 2008; Feb. 12, June 12, and Oct. 12, 2009; Feb. 12, June 12, and Oct. 12, 2010.
This is a renewal of PAR-05-011 and will use the K22 award mechanism. For more information, see http://cri.nci.nih.gov/4abst.cfm?initiativeparfa_id=3823. Inquiries: Belinda Locke - email@example.com
Understanding and Preventing Brain Tumor Dispersal
Application Receipt Dates: Non-AIDS Applications (new): Feb. 5, June 5, and Oct. 5, 2008; Feb. 5, June 5, and Oct. 5, 2009; Feb. 5, June 5, and Oct. 5, 2010.
This is a renewal of PAS-07-196 and will use the R01 award mechanism. For more information, see http://cri.nci.nih.gov/4abst.cfm?initiativeparfa_id=3824. Inquiries: Dr. William C. Timmer - email@example.com
Understanding and Preventing Brain Tumor Dispersal
Application Receipt Dates: Non-AIDS Applications (new): Feb. 16, June 16, and Oct. 16, 2008; Feb. 16, June 16, and Oct. 16, 2009; Feb. 16, June 16, and Oct. 16, 2010.
This is a renewal of PAS-06-201 and will use the R21 award mechanism. For more information, see http://cri.nci.nih.gov/4abst.cfm?initiativeparfa_id=3824. Inquiries: Dr. William C. Timmer - email@example.com
Cancer Prevention Research Small Grant Program
Application Receipt Dates: March 19, July 18, and Dec. 19, 2008; March 20, July 17, and Dec. 18, 2009; March 19, July 19, and Dec. 9, 2010.
This is a renewal of PAR-06-313 and will use the R03 award mechanism. For more information, see http://cri.nci.nih.gov/4abst.cfm?initiativeparfa_id=3825. Inquiries: Dr. Lynn Sorbara (Early Detection) - firstname.lastname@example.com; Dr. Harold Seifried (Nutrition) - firstname.lastname@example.com; Dr. Vernon Steele (Chemoprevention) - email@example.com
Institutional Clinical and Translational Science Award
Letter of Intent Receipt Dates: May 17 and Sept. 21, 2008.
This is a renewal of RFA-RM-07-007 and will use the U54 award mechanism. For more information, see http://cri.nci.nih.gov/4abst.cfm?initiativeparfa_id=3829. Inquiries: Dr. Anthony Hayward - firstname.lastname@example.com
National Quitline Celebrates One Million Calls
1-800-QUIT-NOW was developed by the National Network of Tobacco Cessation Quitlines, the North American Quitline Consortium, the Centers for Disease Control and Prevention, and NCI to help tobacco users quit. Additional information on quitting smoking can be found at http://smokefree.gov/; information on smoking and cancer is available at http://www.cancer.gov/cancertopics/smoking.
Revised OSPA Snapshots Available
Cancer in the Developing World Seminar Now Available Online
The seminar, held on December 20, 2007, featured internationally recognized experts providing an in-depth, informative look at many issues surrounding cancer in less developed countries, including geographic incidence; survival and mortality trends; the state of cancer prevention, screening, and treatment in less developed countries; perspectives on cancer care from Africa, Asia, and India; major international cancer initiatives in prevention, tobacco control, and palliative care; and ASCO and NCI initiatives to address the global cancer burden.
The audio track, slide presentations, bio sketches, and fact sheets from this event are also available through ASCO's online press center. Log on to www.asco.org/presscenter and click on the Meet the Experts link.
A new issue of BenchMarks on the Global Burden of Cancer is also available. Go to http://www.cancer.gov/newscenter/benchmarks-vol7-issue2.
Oregon Health & Science University Cancer Institute
Director: Dr. Brian J. Druker • 3181 S.W. Sam Jackson Park Road, CR 145, Portland, Oregon 97239 • Phone: 503-494-1617 • Web site: http://www.ohsucancer.com/
From its inception in 1992, the Oregon Health & Science University (OHSU) Cancer Institute was conceived as a resource that would draw on its strengths as part of an academic health center and research powerhouse. In 1997, the OHSU Cancer Institute became the only NCI-designated Cancer Center in Oregon. Dedicated to reducing the cancer mortality rate in Oregon by connecting with existing statewide physician networks, the OHSU Cancer Institute's mission is to translate discoveries into better ways to diagnose, prevent, and treat cancer.
The institute is known worldwide for leadership in molecularly targeted therapies, including the most celebrated cancer discovery in a generation: the drug Gleevec (imatinib). Gleevec was developed by Dr. Brian J. Druker, who is JELD-WEN Chair of Leukemia Research and director of the OHSU Cancer Institute. Recently elected to the National Academy of Sciences, Dr. Druker also is a Howard Hughes Medical Institute Investigator.
Research Activities
Patient Care Specialties
Other Notable Programs


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By Michael Arbeiter, Hollywood.com Staff
American Horror Story, the polarizing, exactly-what-it-sounds-like, fantasy horror series from Glee creator Ryan Murphy, has elongated its stay on FX with the announcement of a Season 3. The network confirms that AHS has been renewed for a third installment, consisting of 13 episodes, set to premiere in the fall of 2013.
Murphy's series takes an interesting form, introducing a new venue and set of characters each season for a self-contained, independent ghost story. Season 1 focused on a haunted house with a treacherous past, wreaking havoc on its new residents (married couple Connie Britton and Dylan McDermott and their daughter Taissa Farmiga), while the present second season places its eyes on the darkness lurking within a psychiatric asylum.
So the obvious question: where next?
Amusement Park: A Scooby-Doo mainstay, amusement parks have found their way into the horror genre time and time again. Roller coasters, Ferris wheels, the odd cotton candy machine all perfect territory for macabre histories.
Elementary School: This one will ordain a large number of particularly young starring players, but so long as their acting capabilities are in order, the idea of a haunted grammar school could indeed be doubly frightening. It's always scarier when little kids are involved.
College Dormitory: Conversely, watching 19-year-olds fall victim to a vengeful dead coed might be easier to swallow, but there's the added benefit of some of the teen sexuality with which the Glee creator is so enamored.
Playhouse: Theater is riddled with curses and superstitions. You can't say Macbeth or ""Good luck,"" and there's that whole shebang about warding off spirits with a center-stage ghost light. Rife for parody, and for some energetic (and even musical!) horrors.
Video Game: This one will involve a little more creativity. A multiplayer online game, an original World of Warcraft knockoff, that is infested by a ghostly player who somehow works his way past the onscreen adventures of his opponents and into their actual lives... making them substantially shorter.
Barbershop: Ol' Sal was cut short in his prime by a devastating pompadour accident. And now, he haunts the establishment he used to call home, combing his way into the souls of unsuspecting customers.
Zoo: Haunted animals. Always a winner.
The White House: A new first family takes shelter in the Oval Office, but unbeknownst to them, the Pennsylvania Avenue residence is riddled with ghosts of past presidents, all trying to live out their conflicting legacies in the most horrific of fashions. Ghost Van Buren, not a pleasant sight.
Ice Cream Truck: When you hear that music playing, stay far, far away...
Uncharted Island: They can have a bunch of people stranded there after a plane crash. Maybe the isle has some kind of ghost or monster lurking around, or a creepy society of zealots that has been there for generations. Beams of white light emanating from mysterious caves! Immortal gods! Time-travel! Actually, no. This would never work.
Bodega/Truck Stop: A remote 24-hour establishment that people only frequent during the late hours of the night, sometimes with sordid intentions or mysterious origins. Perfect for some good ol' ghostly encounters.
Snow Globe: This one actually doesn't pose too much of a problem. Just don't drop it.
Cruise Ship: The real horror story is that there's no free buffet!
Where do you think AHS Season 3 should take place?
'American Horror Story' By the Numbers: Bloody Face Is Revealed
'Arrow' React: I See Your List of Evil People, and I Raise You Street Crime
New 'Game of Thrones' Season 3 Poster Revealed: Check It Out!
From Our Partners:Prince Harry's 'Naked Vegas Party Pal' Carrie Reichert Writing a Tell-All Book EXCLUSIVE
Kim Kardashian Flaunts Cleavage in Bikini Top on Instagram: Her 63 Sexiest Twipics (PHOTOS)

subset: commoncrawl


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Thoughts and prayers for the family of Trayvon Martin have been all over social media following Saturday's "not guilty" verdict. In Detroit, a church service was held Sunday to call for an end to racial profiling.
Click on the video player to watch Maurielle Lue's report.
Once the verdict was read there was an explosion on social media, many asking if Michael Vick can go to jail for killing dogs and Plaxico Burress can be jailed for shooting himself, how can a man who killed an unarmed teen be allowed to go free?
Sunday, churches across Metro Detroit held prayer vigils including the Greater St. Matthew Baptist Church in Highland Park. Black youth were called to the pulpit surrounded with love. Church elders laid hands on their young people, a symbolic action in many faiths. "We need to pray for peace, pray for this justice system," said Pastor David Bullock. "What is the life of one of these young people worth? Trayvon didn't do anything wrong."George Zimmerman, Trayvon's killer, was found not guilty of second degree murder, sparking yet another conversation about race in America. Pastor Bullock prayed for both the Martins and the Zimmermans. His service was not only a call to action, but a call for peace and a reminder that young, black men are not disposable.
KTBC FOX 7119 East 10th StreetAustin, TX 78701Phone: (512) 476-7777Fax: (512) 495-7001


text:
- Take a three-day vacation from life to do what you love at the country's best Bead Show
- Hone your skills in jewelry making classes! Find 100+ jewelry making workshops on bead embroidery, metalsmithing, wire weaving, torch enameling and more
- Learn the newest jewelry design techniques and explore the latest jewelry making tools with direction from top-notch instructors
- Shop for beads and jewelry making supplies at the Bead Fest shopping Expo
- Discover one-of-a-kind beads, components and finished jewelry in our Artisan's Alley
Bead Fest is for beaders and jewelry makers of all skill levels! This jewelry making extravaganza brings the top jewelry trends, instructors and beading resources together under one roof!


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I am not sure how, but I managed to lose 1.5 lbs this week.I needed a reminder that getting back on the wagon for four days can be beneficial. I spent the entire week preparing for a conference and recovering from last week's cold. I slipped up with ice cream and cake, but I guess I made up for it with fruit, salad, and some self restraint. Our daughter did her first hike without riding in the backpack this morning. We get more exercise when she rides, but we had a blast Hope you are all doing well. I might be out of the loop a bit until Wednesday.
Current weight: 141.6
Plan: attempt good behavior and conference fun run, then back on the workout wagon at home.


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Can you imagine getting as many as 10 phone calls a day, and all of them are the wrong number? A Henry County couple knows what that feels like.The family's phone number was listed as the contact number for a local store of a national retail chain. The Helton family says they asked repeatedly for the company to change its online number, but nothing happened. That's when Call for Action got involved.A local retailer somehow had 85-year-old Louise Helton's number listed as their own online. In one call that Louis Helton took, it was the retailer's own employee calling the wrong number. But, nothing Louise and her 92-year-old husband Marvin did seemed to fix the problem. "I've been trying for seven long months," said Louise.The feisty Henry County couple took matters into their own hands and called Call for Action. "I have watched Call for Action for years…people getting conned doing their driveways never coming, back. Remodeling, never come back. So, one day I told my daughter, 'I've had it!", said Louise.The FOX 5 group Call for Action heard her. Immediately, the all-volunteer group got to work and in days they got the Helton's phone number pulled from the Internet. With the incident behind them, Marvin says he's going settle in to watch the Braves uninterrupted and Louise plans to get busy spending a gift certificate the company is sending as an apology. "They're going to send me $100. I've got 10 grandkids. I can use it," said Louise.The Call for Action team can help when you've simply can't get a problem resolved. There are two ways to contact them. First, you can go to www.myfoxatlanta.com and put in a request there, or call them at 404-879-4583.
Thanks for contacting FOX 5. To reach our newsroom by phone, please call (404) 898-0100.


text:
Thursday was another bad day for celebrity chef and entrepreneur Paula Deen.
Her $100 million-a-year media and merchandise empire is crumbling under the weight of Deen's racially insensitive remarks and a PR damage control effort that seems to have made things worse.
Three more companies announced Thursday they're ending, suspending, or phasing out business with Deen.
Target, Home Depot, and the pharmaceutical drug-maker Novo Nordisk are the latest of a long list of businesses to distance themselves from Deen.
One analyst estimate's Deen's business revenue has been cut in half, and within the next year could be at 20 percent of what it was before the scandal.
People who are still supporting Deen--and there's a significant number of them--say the scandal is overdone.
It all started after Deen's testimony in a lawsuit that accused her of racism was made public. When asked if ever, in her life, she had used the "n-word" she replied: "yes, of course."
She also came off as nostalgic for the era of slavery when talking about wanting to plan a "southern plantation wedding" with food servers who are, "middle aged black men with white jackets and bow ties."
She said she did not mean anything derogatory.
Things compounded when her attempts to explain herself came off, at various times, as contrived, unapologetic, accusatory, defiant, and just inconsistent.
From the get-go, the media and people on social media were there to pick Deen and her missteps apart.
We asked an expert in media and media psychology if the scale of the rebuke against Deen is out of proportion. He said reactions to almost everything in our culture is out of proportion.
One of Deen's mistakes, he said, was not knowing that.
"What she did was stupid and it was also offensive," says psychologist Dr. Stuart Fischoff. "And it was also something which she should know more about. That's the contract you sign when you become a celebrity. That you have to be aware of how you walk, talk and think and act."
Follow @fox32news
FOX 13 / WTVT-TV3213 West Kennedy Blvd.Tampa, Florida 33609Main: (813) 876-1313Newsroom: (813) 870-9630Fax: (813) 871-3135


text: Philomena is the story of a woman looking for her son after he was taken from her as a child. The movie is directed by Stephen Frears, who also directed High Fidelity and The Queen (both excellent movies). Dame Judi Dench plays Philomena and the movie also stars Steve Coogan. I find Coogan to be a hilarious comedic actor and if you haven't had the chance to check out Hamlet 2, you definitely should.


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Italian POW Internment Camp Compound No.II U.S. GOVERNMENT PROPERTY THIS PHOTOGRAPH WAS PRODUCED AT GOVERNMENT EXPENSE AND ANY MISUSE THEREOF MAY RESULT IN DISCIPLINARY ACTION UNDER THE APPROPRIATE ARTICLE OF WAR. NINTH SERVICE COMMAND OFFICIAL PHOTO ARMY PICTORIAL SERVICE If published CREDIT U.S. ARMY SIGNAL CORPS Do not publish unless authorized by Military Intelligence Dept. File No. 9SC-44-UASFD- 1802
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Roasted Vegetable Medley
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A medley of fire roasted vegetables including carrots, cauliflower, sugar snap peas and pepper strips in a seasoned butter sauce are the perfect complement to any meal!
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End-of-Life Care: Writing Your Own Last Act
Corinne and Jack Sweet
tags: General Audience, Seniors
1,052 people like this -Like
Planning for the end of life is very important, but can include some difficult decisions and conversations regarding future care for yourself or a loved one. Presented by Dr. Amy N. Cowan, a Geriatric Fellowship-Trained doctor at the University of Utah, this seminar will help you plan for this inevitable life event by addressing the following topics:
Please join us and be part of the conversation.
Amy N. Cowan, MD is a practicing geriatrician with a passion for improving communication between doctors, patients and their families. Dr. Cowan is Certified by the American Board of Internal Medicine (ABIM)
Location: Corinne and Jack Sweet Branch
Contact Information: 801-594-8651


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All our rooms have en suite shower/WC and 2 rooms have disabled access. We have a selection of single, double and multi-bedded rooms.
The kitchen offers buffet breakfast as well as half and full board, vegetarian meals on request.
We offer many sports and leisure activities: sports ground with Astroturf, TV lounge and common room with table football, table tennis.
Please note:
Cancellation policy: 24h advance notice
Payment upon arrival by EC-Karte, credit cards or cash
Breakfast Included
Taxes not included
The TreeHouse Backpacker Hotel
Aalfang, Austria Youth Hostels
The TreeHouse offers year round fun. Adventure Tours, Skiing, Snowboading, Hiking, Biking or sitting in the shade with a cool drink for those less adventurous types....
Starting at 21 Per Night
Hostel Ruthensteiner
Vienna, Austria Youth Hostels
Only 3 minutes walk from Westbahnhof Train Station & a short walk from the City Center and beautiful Palace Schoenbruenn, this is "The Friendly Hostel" with a Great International Atmosphere! Make yourself at home in our smoke-free environment!...
Starting at $11 Per Night
Vienna, Austria Youth Hostels
The Porzellaneum hostel is located in the centre of Vienna near all the famous tourist sights....
$21 Per Night
Palace Hostel
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We have 41 rooms with 4 beds in our hostel which has probably the best location in Vienna......
$18 Per Night
Do Step Inn
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The Do Step Inn is small, cosy and friendly budget accommodation with a cental location in Vienna......
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Hostel Hutteldorf
Vienna, Austria Youth Hostels
We have 60 bright, friendly rooms with either 2, 4, 6 or 8 beds in an awesome location......
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Yoho International Youth Hostel Salzburg
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With its location right between train station and old town, both just a 10 min. walk, the Sound of Music movie and tours daily, a hostel bar and a great international atmosphere the YoHo is easy to find and hard to leave. ...
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Jufa Salzburg
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Are you searching for the closest hostel to the old town with great offers such as Neat Accomodation, Happy Hours, Great Meals, Best Price for Tours?...
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Wombats City Hostel Vienna - The Lounge
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Bad Ischl, Austria Youth Hostels
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Austria: Passau to Vienna Bike - Freewheeling Adv.
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Cycling and walking holidays in Europe
Salzburg, Austria Bike Tours
Guided and self guided cycle, walking and road cycle programs all around Europe. We also offer mountain hotels in Austria, Germany, Italy and Switzerland...
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Vienna to Budapest Cycling Tour with Freewheeling
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WINTER TOUR EUROPE - ADVENT Vienna,Budapest,Zagreb
Vienna, Austria Cultural Experience
Our winter escorted tours include special events and activities during Advent, Christmass and New Year holiday. Enjoy snowy winter landscape and Europe magical cities filled with unique cultural trasure: Vienna,Budapest,Zagreb,Bratislava,Ljubljana......
Trekking in Sikkim (India)
Carinthia, Austria Sight-Seeing Tours
We organize a variety of adventure travel and sight-seeing activities including trekking, peak climbing, expeditions, glorious mountain flights, white water rafting, jungle safari, and trips to Nepal, Tibet, Bhutan, Doors, Goa, and Leh- Ladakh. A...
Starting at $60 Per Night
Kogelhuber Luxury B&B
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Gay Vacation appartment at the south styrian wine route....
30 Per Night/Pers
EUROCYCLE - Explore Europe by Bicycle
Danube Valley, Austria Bike Tours
Explore Europe by bicycle! Organized bike tours & Bike&River cruises throughout Austria, Germany, France, Netherlands, Portugal, Spain, France, Italy, Greece & beyond! Tours include accommodation, meals, daily luggage transfer, bike rental & more....
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CROCODILE SPORTS Oudoor Adventure GmbH
Salzburg, Austria Rafting Trips
We offer a wide range of outdoor activities in the beautiful surounding countryside of Salzburg - it's an Outdoor Paradise; Come and enjoy it! Activities provided year round, from easy, moderate to challenging. Rafting, Canyoning, Paragliding .........
Fantastic ski breaks in charming Alpine chalet
Carinthia, Austria Hotels & Resorts
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Beautiful Guesthouse in mountain Austrian village
Salzburg, Austria Bed & Breakfasts
Haus Patricia is a beautiful guesthouse offering B&B and Self catering self contained Apartments.Situated in the lovely Austrian alpine village of Lofer Nr Salzburg.Central for excursions to nearby Zell am See,Kitzbuhel,Berteschgarten,St Johann,Salzb...
28 Per Night
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Moving Up: Fordham's 2011-12 Sponsorship Accountability Report
November 13, 2012
"Moving Up" is The Thomas B. Fordham Foundation's charter school sponsorship accountability report for 2011-12. Through it, we hope to help readers understand the complexities of charter schools and better appreciate the hard work of the teachers, school leaders, and board members who serve not...
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Student Nomads: Mobility in Ohio's Schools
November 07, 2012
Student mobility happens when kids change schools for reasons other than customary promotions. The change of schools may occur for any one of a multitude of reasons--anything from a simple change of address, to seeking out a nicer school or neighborhood, or due to family turmoil. These school...
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Applying Systems Thinking to Improve Special Education in Ohio
Nathan Levenson
September 04, 2012
Special education is a maze of complexity, highly bureaucratic and compliance driven, often a point of contention between educators and parents, frequently litigious, and the single fastest growing portion of spending on public education. It has been largely impervious to change or improvement...
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Future Shock: Early Common Core implementation lessons from Ohio
May 18, 2012
The Thomas B. Fordham Institute has long advocated for high quality academic content standards nationally- and in our home state of Ohio. The Buckeye State committed itself to adopting more rigorous academic content standards in 2010: Ohio is one of 45 states and the District of Columbia that has...
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Teacher Compensation Based on Effectiveness: The Harrison (CO) School District's Pay-for-Performance Plan
March 14, 2012
A teacher's effectiveness has a tremendous impact on a child's learning and academic trajectory. Yet knowing that, and being able to create teacher evaluation systems that successfully measure and document teacher effectiveness, are two very different things. In fact, for as long as anyone can...
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Better Choices: Charter Incubation as a Strategy for Improving the Charter School Sector
Terry Ryan
December 08, 2011
The twenty years since Minnesota passed the nation's first charter school law have seen a great expansion in school choice, with charters operating in all but ten states and enrolling nearly two million students nationwide. Yet while parents now enjoy more schooling options for their children, a...
Charter Schools Sorely Test Dayton
December 07, 2011
Checked Out: Ohioans' Views on Education 2009
December 07, 2011
Governor Ted Strickland and state legislators are seriously debating the future of the Buckeye State's public education system--and much of that debate has grown more partisan than is probably healthy for the state and its children. Much of it also centers on money. But what do Ohio's voters,...
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Fwd: How Are Dayton's Charter Schools Doing?
Terry Ryan
December 07, 2011
This edition of Fwd summarizes Ohio state report card data for Dayton public schools district and charter. Two major conclusions leap from these data. First, despite some recent gains, the phrase academic emergency continues to characterize the majority of Dayton's public schools. Second,...
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Two Steps Forward, One Step Back: Fordham's 2010-11 Sponsorship Accountability Report
Kathryn Mullen Upton
Terry Ryan
November 22, 2011
The 2010 elections were good for Republicans in Ohio, who have traditionally supported the expansion of charter schools (and choice broadly). We were hopeful as lawmakers and the governor set about removing caps on charter schools, lifting the e-school moratorium, and suggesting other legislative...
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text:
WISCONSIN DELLS, Wis. – Senior Sam Barber (Schofield, WI/D.C. Everest/Winona St.) tallied 21 points for the Pointers as the UW-Stevens Point women's basketball team cruised to a 74-35 victory Thursday evening over the Engineers.
UWSP went on a 12-0 run to start out the game, building its first half lead to as many as 23 points, which came with one minute remaining in the half.
Barber, who played just 15 minutes in the contest, went 9-for-12, including 3-for-4 from beyond the arc and pulled down five rebounds.
Jamie Destache (Sussex, WI/Sussex-Hamilton) recorded a career-high 11 points going 5-for-6 from the field and Josi Schultz (Eau Claire, WI/Memorial) chipped in with 10.
Eleven different Pointers tallied a basket in the victory as the Pointers gradually built their second half lead to 39 points to end the game.
Three different MSOE players tallied double digits as Megan Kroll led the way with 12 points.
UWSP returns to action Friday against Ripon College in the Wisconsin Dells. Action set for 7:30 p.m.
The following link takes you to UW Stevens Point athletics: http://athletics.uwsp.edu/news/2012/12/27/WBB_1227125908.aspx?elinkdata=63012


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British Broadcasting CorporationHome
A behind the scenes look at Penny's festive living room.
After missing the courier delivery of her Christmas gifts, Miranda...
Miranda interviews her sitcom family at Christmas.
Visit the Miranda page to find out more about the show.
BBC © 2014 The BBC is not responsible for the content of external sites. Read more.
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Whether it's Michigan or Louisville players cutting down the nets after Monday's big game, the new national champions will be using a very special ladder."This ladder is a custom nine-foot ladder," said Stacy Gardella from Werner Ladder Company. "We build an eight-foot ladder and ten-foot ladder that are available in stores. This is totally unique to the NCAA."This year is the 75th anniversary of the NCAA tournament, and the ladder bears the names of every championship team."Because it was such a memorable year, we said we've got to commemorate it in such a special way," Gardella said.Where does the ladder go after the nets are cut down?"The winning school... will have it... for eternity," Gardella explains.The ladder is actually painted yellow and blue. That is totally coincidental. I'm told Werner Ladder has a trademark on yellow and blue ladders. However, John Beilein and the Wolverines probably think it would look great over at Crisler Arena.
205 N. Michigan AvenueGround FloorChicago, IL 60601Station Operator: (312) 565-5532Newsroom: (312)565-5533


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But first, to redeem myself, here's a recipe for a healthy breakfast. I'm always looking for ways to sneak beans and veggies into food. My son is an athlete and he needs staying power to fuel his long days. I created this pumpkin pie oatmeal recipe just for him. The two strange things about this recipe are that there's no pumpkin involved and I found a way to pack in a 1/2 cup of beans in each serving.
2 large or 3 small servings
2 large carrots
1 c cooked white beans
2 c water
Pinch salt
1 1/3 c old fashioned oats
1 t cinnamon
Pinch cardamom
Pinch cloves
1/8 t nutmeg
½ t balsamic vinegar
Sweetener or Stevia to taste ( I use Kal Stevia Powder )
2 t coconut oil
Blend the carrots, white beans and water until totally smooth. Pour into saucepan along with the oats and spices. Heat over medium heat stirring now and then to prevent sticking for around 20 minutes. Stir in the balsamic vinegar and sweetener. Add 1 t coconut oil per serving.
Calories 406
Fat 9 grams
Carbs 66 grams
Fiber 17 grams
Protein 16 grams
Now that the nice is out of the way, here's the naughty!
Gluten Free Brownies
1/2 C golden flax meal
1 ¼ c rice milk
2 1/2 c sugar
¾ c cocoa
1 T instant coffee
1 c oil
1 t salt
pinch pepper
2 c Bob's Red Mill All Purpose Baking Mix
1 c chocolate chips
1 t baking powder
Method: Pre-heat oven to 350 ( use an oven thermometer to check temperature )
In a mixing bowl, add the flax, milk, sugar, cocoa, coffe and oil, salt and pepper. Whisk together really really well. Let mixture sit for 15 minutes or so. Now stir in the GF baking mix, chocolate chips and baking powder. Again, stir really really well. Pour into a greased 9 by 13 baking pan and bake for 30 minutes. Rotate pan halfway through. It is very important to allow the brownies to cool, overnight is best if possible. Cut into 16 squares and enjoy!
So there ya have it! This week I will be back to posting healthy food again!


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You're leaving Wedding Paper Divas to see the Deal of the Day at our parent site, Tiny Prints.
You won't be able to dismiss this by usual means (escape or click button), but you can close it programatically based on user choices or actions.
"I love these invitations! They quality is better than I expected and they look more expensive than they really are! The classic look of this design is just perfect for what I have in mind for my wedding. I can't wait to send these out to everyone."
"Even though this is really a wedding invitation, we changed some of the wording to make it an invitation to our huge after party immediately following the wedding at a different location. Due to space confinements at the wedding venue and a guest list way longer than the wedding venue will accommodate, we are using these to invite all our friends that we want to be a part of our special day to come to the after party and celebrate with us. It's a fun, whimsical and joyful looking invitation which is exactly what we are wanting to portray with the after party celebration."
"I love these invitations! This design is simple and elegant. The foil stamp lettering and lines combined with the exceptional quality paper gives the invitations a very high end look and feel. It was so easy to add, delete and change text from the invitations and The RSVP cards. They even provided me with two options for the orientation of the RSVP card. The entire process from start to finish was easy and hassle free. WPD responded very well to my design instructions; they were efficient, professional and great to work with. I would highly recommend this design and would not hesitate to work with WPD again in the future."
"Love the invitation and the fact that you can customize it so easily. The wording and colors can be changed in any way to fit exactly what you want. Awesome product!!"
"Our invitations turned out beautiful ! We used a mint green color for the back (solid) and our the font was a charcoal grey. They turned out great and the professional designer edited our etiquette and spelling!"


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Franklin County Bar Association
Melvin F. Wilhelm
459 Main Street
Brookville, IN 47012
Disclaimer: As a courtesy to local bar associations statewide, the Indiana State Bar Association (ISBA) has agreed to furnish local bar Web pages. The content is provided by each local bar association; however, the ISBA does not warrant the accuracy of said content. The ISBA will monitor local bar sites only for inappropriate content.


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Quick Links
Shop All Jewelry
No accessory is more eye-catching than the perfect sparkle of cubic zirconia necklaces. Eve's Addiction offers a wide selection of sterling silver cubic zirconia necklaces in many popular and classic styles, made with quality cubic zirconia stones of every shape and color. Whether you're looking for a trendy cubic zirconia palm tree pendant or a classic, sparkling cz journey necklace, you'll find it at EvesAddiction.com. Our cubic zirconia pendants make great gifts for your loved ones as well. If you love the sparkle of diamonds but don't love the price, our cubic zirconia necklaces are for you!


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Software Map
Tag cloud | Project Tree | Project List
Project tree
Now limiting view to projects in the following categories:
Topic :: Database Administration :: Database Monitoring [Remove This Filter]
Environment :: Console (Text Based) [Remove This Filter]
Intended Audience :: Database Administrators [Remove This Filter]
Natural Language > English
Browse By:
7 projects in result set.
|0. pgstatspack - Pgstatspack is the essential statistics package for performance analysis.
|Activity Percentile: 62.70
Activity Ranking: 48.00
Registered: 2008-05-03 09:12
|1. PostgreSQL Toolbox - A collection of small programs to aid the PostgreSQL administrator and developer.
|Activity Percentile: 61.90
Activity Ranking: 49.00
Registered: 2008-05-08 07:26
|2. SNMP agent for PostgreSQL - The SNMP(Simple Network Management Protocol) agent for PostgreSQL.
It reports the health state of PostgreSQL with original MIB(Management Information Base).
|Activity Percentile: 60.32
Activity Ranking: 51.00
Registered: 2005-12-06 01:02
|3. pgsnap - pgsnap is a PostgreSQL tool that mimics orasnap performance report tool for Oracle.
|Activity Percentile: 53.97
Activity Ranking: 59.00
Registered: 2008-04-01 22:23
|4. PGSpy - PGSpy uses libpcap to sniff out and display the queries being sent to a database - provides functionality similar to log_statement in postgresql.conf however it is not invasive and does not clutter your logs.
|Activity Percentile: 13.49
Activity Ranking: 110.00
Registered: 2005-04-06 18:25
|5. PostgreSQL Database Administration Tools - pgtools is a package with usefull utillities for manteining, monitoring, and administrate PostgreSQL database clusters.
|Activity Percentile: 12.70
Activity Ranking: 111.00
Registered: 2005-11-28 16:28
|6. pgLoggerCSV - pgLoggerCSV é um dameon em Linux que pega o log do Postgres e salva em uma tabela no próprio Postgres de forma automática, usado para monitoramento via query.
|Activity Percentile: 9.52
Activity Ranking: 115.00
Registered: 2010-03-31 16:37


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It's too soon to even begin to figure out why, but it's time for schools to figure out how to seal themselves from threats like the one that led to the massacre in Newtown Connecticut.
Today many schools across Metro Detroit are feeling anxious as students return to classes after the Sandy Hook Elementary School shooting.
Schools are calling on police officers. Staff sits inside listening to emergency scanners – most with the doors locked.
Watch the video for FOX 2's Roop Raj's full report.


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Description:IBM Intel Xeon Full Processor Option Kit w/VRM and heatsink Xeon E5520 2.26GHz 1066MHz 8MB L3 Cache for System x3400 M4 and x3500 M3Part Number(s)IBM Part# 46D1352
HP Processor Kits:
Manufacturer Part# 46D1352
This is the full processor option kit. It includes the
Processor(s), Heat-Sink(s), Fan(s), Thermal paste
and VRM (Voltage Regulator Module) where required.
Overview:The platform of choice keeps getting better. Designed for dual-processor server and workstation platforms Intel Xeon processors give you the freedom to focus more on your business and help you gain greater flexibility and lower costs. Put the Intel Xeon processor's latest platform innovations to work to accomplish more than ever before.
CategoryIBM Processor
Generation2.26 GHz
Part Number46D1352
Products ID459395
Product TypeProcessor Upgrade
Front Side Bus Speed1066MHz
Processor TypeXeon
Product TypeXeon
Clock Speed2.26GHz
Processor Instruction Set
L3 Cache Size8MB
Processor CoreQuad-Core


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Victoria's Secret Model Gives Up Career for GOD! - Inspirational Videos
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This Adorable 2-Year-Old Knows How To Praise God! At 1:05, I Was Yellin' AMEN! - @ourprecioussavior
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Press the button below if you liked this video! Thank you! =D
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Posted By ourprecioussavior 2013-05-15T11:49:05
Kylie Bisutti had the career that most girls and women dream of. But it was interfering with her relationship with God and that was most important to her...so she gave it up to glorify HIM! What an amazing testimony. God bless you Kylie!
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Assistant Controller Jobs
6 Assistant Controller jobs found on Monster.Jobs 1 to 6 of 6
nLIGHT Vancouver, WA, 98660
Summary Own completion and continuous improvement of worldwide consolidations. Streamline AP and other transaction processing. Grow level of systems competency within the accounting team. You will be responsible for managing the day to day accounting processes of nLIGHT's expanding businesses in Vancouver, Washington and Hillsboro, Oregon. You need to be a hands-on professional who will ensure p...
Assistant Controller - CPA - Career Position. --The key responsibilities include: financial business case consolidation, net present value analysis and cost/investment reporting and tracking. The candidate is also responsible for: (a) communicating the program financial position to senior management and other functional operating teams; (b) compiling vehicle margin inputs including revenue, varia...
Rock-Tenn Saint Paul, MN, 55102
Assistant Controller St Paul, MN RockTenn (NYSE: RKT) Norcross, GA RockTenn is one of North America's leading manufacturers of paperboard, containerboard, consumer and corrugated packaging and one of the world's largest paper recyclers. Over the years, Rock-Tenn has outpaced its peers in revenues, profitability, EBITDA and stock price. We've done this by creating and following a bold strategy ...
Job Summary: Reporting to the Manager, Divisional Assistant Controller, the Financial Analyst is responsible for various financial analysis and assisting with annual budgets. In addition, this role is responsible for various financial models and tools to streamline financial management process. The detailed position responsibilities are as the follows: Duties and Responsibilities: Create and pr...
Amyris Emeryville, CA, 94608
Corporate Controller FA14-002 Amyris is an integrated renewable products company focused on providing sustainable alternatives to a broad range of petroleum-sourced products. Amyris uses its industrial synthetic biology platform to convert plant sugars into a variety of molecules -- flexible building blocks that can be used in a wide range of products. Amyriss initial portfolio of commercial pro...
Caesars Entertainment Corporation Las Vegas, NV, 89134
JOB SUMMARY: Reporting to the Vice President / Assistant Controller, you will join a team that includes another Director, Technical Accounting. In summary, you will act as a proactive partner with the leaders of the Company, serving as the first point of contact on technical issues related to business development and merger and acquisition activities. You also will assist with the evaluation and ...
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Assistant Controller
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All those summer outlet sales, curling bags, squeezing into jeans and swiping your cards can take it's toll on your muscles and bank account.
Thank Paul Lorimer-Wing, easyGym 's Ceo in Oxford for creating the retail routine . Just 30 minutes get's you warmed up, curled up, twisted out, and stepped up to get your shopping muscles beefed up for back to school shopping.
photo courtesy-fitnessmagazine.com, http://www.beautyandconfidence.com


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1 in 26. The Institute of Medicine estimates this to be the number of Americans who will develop epilepsy. One of the largest and most lucrative fundraiser's in search of a cure for epilepsy took place here in Chicago this summer, shattering the million dollar ceiling, and raised $1.1 million.
So what is epilepsy and how has this medical condition received such a prominent place in Chicago fundraising? Epilepsy is broadly defined by the National Library of Medicine as a brain disorder in which a person has repeated convulsions over a period of time because the brain sends out abnormal signals. The disturbed brain activity can cause changes in attention and/or behavior. And while epilepsy remains a puzzling diagnosis with little hope of a permanent cure much of the time, inroads are quietly being made. For example, patients with epilepsy whose seizures aren't controlled with medications may be helped by a high-fat, very-low-carbohydrate diet called a "ketogenic diet," nerve stimulation, biofeedback or surgery. By far, though, the most common way seizures are kept at bay is with medications. These developments are only made possible by funding. And that's what brought out the Chicago philanthropists and socialites to Navy Pier to attend the 14th annual Chicago Benefit for CURE (Citizens United for Research in Epilepsy). The history of epilepsy charity in Chicago is the story of a little girl and a mother desperate to help her. It's the story of Susan and her daughter, Lauren, which has been chronicled numerous times but still doesn't lose its poignancy. When Lauren fell ill at 7 months old, her parents were advised to give her a partial dose of an adult cold medication, after which incessant and intermittent seizures rocked her little body – and her parents' world – for years. The irony is that in later years, the FDA would come out and warn parents not to give their children over-the-counter adult strength cough and cold drugs because they contained substances that might be harmful. The guilty ingredients? Carbinoxamine, pseudoephedrine and dextromethorphan.
When little Lauren became one of roughly half a million children younger than 15 who develop epilepsy each year, Susan sprung to action. She co-founded CURE in 1998 and recruited to the cause A-lister elected official friends, celebrities and journalists. Her outreach and influence has paid off. In total, more than $18 million has been raised and 126 research grants have been funded by CURE. At this year's Navy Pier event that was headlined by legendary singer/songwriter Carole King, each attendee had his or her own personal reason for joining in the cause.
Tammy Duckworth, Democratic Congressional Candidate for Illinois' 8th district, is a veteran and head injury victim. "Ever since I became disabled, I became interested in any injuries that led to disability," she explained. "Brain injuries have led to a rise in epilepsy in our wounded veterans and I work with veterans groups."
John Rogers of Ariel Investments, said he has had a long term relationship with Susan and her husband, David. "I'm here to support them. And I love Carole King!"
Bob Beavers of Beavers Holdings told me "I'm here to support the cause of my close friends and to help the children affected by the disease. It's going to be a fun evening to be with a lot of friends."
Two of those friends, Western Springs middle-schoolers Jeffrey Vitek and Charlie Mavon, raised thousands of dollars for their classmate Hugh O'Donnell, who has epilepsy. They received a standing ovation when their story was told on stage.
Congresswoman Jan Schakowsky is interested in the scope of the mission. "CURE has done a great job in funding very important research to find not just a cure for epilepsy, but also for other neurological conditions."
Alderman Ed Burke says he has been to every CURE Annual Benefit since the inception 14 years ago. "I think Susan's vision in expanding research in epilepsy is now beginning to have significant results – public awareness and knowledge that comes with it. It raises awareness that it is a national health problem."
And although it's estimated that epilepsy costs the U.S. about $15.5 billion annually, some might consider that calling it a national health problem is an understatement, as it claims overseas lifestyles as well. The World Health Organization states that up to 94 percent of patients with epilepsy in developing countries do not receive appropriate treatment. Ninety-four percent!
Takayoshi-san Oshima, a benefit sponsor and entrepreneur who sells IT infrastructure through his company Allied Telesis, said that his involvement is good for business. "We're here to do some good for the world and it benefits us because we get to meet people involved in healthcare."
Dinner Chair Bill Daley highlighted what differentiates the CURE benefit from other charities. "Funds raised at this event overwhelmingly go to research. The issue with epilepsy is that there are so many forms. Most money that was spent before was to find out how to treat epilepsy. When Susan got involved, she wanted resources to be used towards finding a cure."
Funding research is a core mission of CURE, and the field is becoming more competitive, said Susan, in her general address to the attendees. "In our first year, in '98, we received just a handful of applications from scientists for funding. This year, we received 150, from brilliant scientists around the world, who are poised and ready to find solutions. This year, we' re investing $3.5 million in research---more than we've ever funded before."
Lauren is now 31-years-old. The picture of her father, she lives in Miserocordia, a Chicago residence for the developmentally disabled, and even has a boyfriend or two. Her epilepsy is now controlled. For more information, go to www.cureepilepsy.org.
KDFW FOX 4400 N. Griffin StreetDallas, Texas 75202
Main Station Directory:(214) 720-4444News Fax:(214) 720-3263 or (214) 720-3333


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