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Tumors May Promote Inflammation to Evade Detection
A new study suggests that inflammation triggered by a protein found in many human tumors may help the tumors grow and avoid attacks by the immune system.
The protein, interleukin (IL)-23, represents an important link between inflammation and cancer, the researchers say. And it may help explain why cancers tend to occur in tissues that have been damaged by chronic inflammation.
In the study, researchers from Schering-Plough Biopharma in California found that IL-23 has an increased presence in many types of human tumors. The protein may cause inflammation around tumors that, among other things, protects them. Read more
Guest Update by Dr. Craig W. Reynolds
NCI-Frederick: Helping to Transform Cancer Research
The 10th annual Spring Research Festival on the NCI campus in Frederick, Md. (NCI-Frederick), kicks off later this week. The festival has become a welcome tradition and a great way for those on campus to highlight a unique component of NCI and its mission.
Approximately one-third of the laboratories of principal investigators from the Center for Cancer Research (CCR) are located at NCI-Frederick. But that is just one small part of a much larger operation. Over the last 5 to 10 years, in fact, our campus has undergone a significant transformation. Read more
Tumors May Promote Inflammation to Evade Detection
A new study suggests that inflammation triggered by a protein found in many human tumors may help the tumors grow and avoid attacks by the immune system.
The protein, interleukin (IL)-23, represents an important link between inflammation and cancer, the researchers say. And it may help explain why cancers tend to occur in tissues that have been damaged by chronic inflammation.
In the study, researchers from Schering-Plough Biopharma in California found that IL-23 has an increased presence in many types of human tumors. The protein may cause inflammation around tumors that, among other things, protects them.
"Tumors are apparently using inflammation to escape the normal surveillance done by immune cells," says study co-leader Dr. Martin Oft.
Discovered 5 years ago, IL-23 controls a number of genes involved in the body's response to infection and other challenges. In many cases, says Dr. Oft, the immune response basically starts with IL-23.
The protein also plays a critical role in causing inflammation associated with autoimmune disorders such as Crohn's disease, multiple sclerosis, and rheumatoid arthritis, where the body essentially attacks itself.
"We know that IL-23 drives the inflammation that causes the tissue damage in autoimmune disorders," says Dr. Robert Kastelein, who co-led the study. "And it does the same thing in tumors."
By promoting inflammation, he says, tumors are able to induce new blood vessels, a process called angiogenesis that is critical to both cancer and fighting infections.
When the immune system mobilizes, one of the first changes in the local area is the formation of new blood vessels and the recruitment of inflammatory cells to help fight the infection. Under normal circumstances, this inflammation is then suppressed and educated immune cells arrive to "mop up" the infection.
But tumors, on the other hand, perpetuate the inflammation around them and never make it to the step when tumor-eliminating immune cells arrive on the scene.
The researchers found that mice born without IL-23 were protected against cancer. The mice were also protected when their IL-23 was blocked by antibodies, suggesting that a similar strategy might one day be possible against human cancers.
In the absence of inflammation caused by IL-23, the researchers conclude, immune cells can do their jobs and kill precancerous cells.
The findings, published online May 10 in Nature, come at a time when many researchers are investigating the relationship between cancer and chronic inflammation and the biological processes they seem to share.
"People have felt for 100 years that there's a link between inflammation and cancer, but I don't think anyone has known exactly what that link was," says Dr. Oft.
"We think this molecule is a key link that brings it all together," he says.
By Edward R. Winstead
Guest Update by Dr. Craig W. Reynolds
NCI-Frederick: Helping to Transform Cancer Research
The 10th annual Spring Research Festival on the NCI campus in Frederick, Md. (NCI-Frederick), kicks off later this week. The festival has become a welcome tradition and a great way for those on campus to highlight a unique component of NCI and its mission.
Approximately one-third of the laboratories of principal investigators from the Center for Cancer Research (CCR) are located at NCI-Frederick. But that is just one small part of a much larger operation. Over the last 5 to 10 years, in fact, our campus has undergone a significant transformation.
NCI-Frederick has rapidly become one of the preeminent Federally Funded Research and Development Centers, or FFRDC, in the United States. FFRDC is a congressional designation that provides NCI-Frederick with unique abilities to form and facilitate partnerships with industry and other federal agencies to promote and advance biomedical research.
As such, one of our most valuable assets is the ability to step into situations and provide novel mechanisms for launching important programs or initiatives that, for a variety of reasons, could not be implemented using typical mechanisms, such as a grant or contract.
One excellent example was highlighted last year in the NCI Cancer Bulletin: the establishment of a new synchrotron at the Argonne National Laboratory in Chicago that uses x-ray crystallography to determine protein structures. NCI-Frederick played a central role in making this possible, coordinating an effort that involved two NCI divisions, two NIH institutes, two federal agencies, an activity at an extramural site, and a piece of state-of-the-art equipment purchased from a foreign company.
NCI-Frederick houses the world's largest high-performance computing center dedicated solely to biomedical research, the Advanced Biomedical Computing Center (ABCC). This system supports 1,800 researchers, including those from NCI, other NIH and federal government agencies, and hundreds of NCI-funded extramural investigators.
In addition, there are two biopharmaceutical production facilities on campus to support the drug development efforts of NCI intramural researchers, NCI-funded extramural investigators, small biotech companies, and the National Institute of Allergy and Infectious Diseases' vaccine research program.
As part of our Research Technology Program, we offer such advanced services as proteomics, molecular imaging, analytical chemistry, high-throughput gene sequencing and genomic analysis. These primarily are used by investigators from NIH and other federal agencies, but also can be made available to extramural investigators.
Other NCI programs at NCI-Frederick include the Developmental Therapeutics Program, which has contributed to the development of nearly 40 anticancer drugs, and the Natural Products Branch, which makes its expansive library of natural products available to industry and academic investigators to screen for anticancer activity. In both instances, these are materials that typically cannot be obtained elsewhere by investigators.
We have ambitious goals for the future. We hope to become a major resource for training cancer researchers on the use of new advanced technologies. We also hope to engage in more public-private partnerships aimed at finding novel uses for advanced technologies, and then adding those technologies to our research repertoire. And, finally, we hope to significantly increase our involvement in the area of systems biology, using the ABCC to develop complex mathematical models that will allow us to reverse engineer and visualize how cancer cells develop and proliferate.
I'm extremely proud to be part of the work being done at NCI-Frederick and the important role it plays in advancing cancer research. It is a truly rewarding position, and I believe our most important work is yet to come.
The Curious Rise of Esophageal Adenocarcinoma
An incidence chart of major cancers in the United States over the past three decades shows lines that are mostly flat or moderately sloped. But if the incidence of a relatively uncommon cancer, esophageal adenocarcinoma (EA), is added to the graph, the contrast is stark. After all, rarely do incidence rates of any disease, let alone a type of cancer, increase by 300 to 400 percent in 30 years.
Already infamous for being one of the most lethal types of cancer, these stunning gains in incidence have garnered EA a reputation as a looming threat.
"There are a lot of issues at play as to why those numbers have gone up," says Dr. Nicholas Shaheen, director of the Center for Esophageal Diseases and Swallowing at the University of North Carolina at Chapel Hill. "But I am concerned because we haven't been able to figure out what's causing the increase."
Epidemiologic studies have identified several factors that significantly increase EA risk, says Dr. Wong-Ho Chow, of the NCI Division of Cancer Epidemiology and Genetics. A 1999 case-control study conducted in Sweden, for instance, found that long-standing and severe reflux symptoms increased EA risk by more than 40-fold. When coupled with overweight or obesity, the risk increase jumped to more than 100-fold. Several studies have shown that smoking is also an important risk factor.
While these are risk factors for what is still a fairly rare cancer - approximately 7,000 new cases a year, mostly late-stage disease - it's as if something has happened to unleash what was once nothing more than a medical anomaly.
"The only change in Western society that really mirrored this increase in incidence is the epidemic of obesity," says Dr. Shaheen. "And that makes it the most logical candidate for why things are going the way they are. But we really don't know that. It's still just a theory at this point."
According to Dr. Chow, for a significant portion of patients, EA is thought to begin with reflux, which causes acid from the stomach to spout up into the lower portion of the esophagus. The acid displaces cells that line the lower part of the esophagus - just above where it meets the stomach - with a different, potentially cancerous cell type in a condition known as Barrett's esophagus.
People with Barrett's esophagus have at least a 30- to 40-fold increased risk of developing EA compared with the general population; however, their overall risk is very low: 90 to 95 percent of patients will never develop the cancer.
Unfortunately, most people who develop EA don't have symptoms until they already have late-stage disease, at which time the few available treatment options are not very successful. Even for patients who are amenable to treatment, 5-year survival ranges from just 5 to 30 percent.
A handful of investigators who have been involved in studies with Barrett's patients are searching for molecular indicators that might predict the likelihood of somebody with chronic reflux or Barrett's progressing to EA. At the University of Southern California/Norris Comprehensive Cancer Center, Dr. Peter W. Laird and colleagues are using a test called MethyLight to see if certain changes in the extent of DNA methylation - a way to activate or deactivate genes - can detect EA in its earliest stages or predict the likelihood of progression.
At Fred Hutchinson Cancer Research Center, Dr. Brian Reid, who heads the Center's Barrett's Esophagus Program, and colleagues are examining biopsy samples to determine whether mutations in two genes (p16 and p53), as well as abnormalities in the amount of DNA in a cell - that is, a condition called aneuploidy - are predictive of progression to EA.
Because EA is still so rare, much of this work is really about surveillance, Dr. Reid notes.
"If we can reassure those people who are at low risk, and get high-risk people into appropriate surveillance or treatment options, it would be a big help," he says.
The only current option for screening of people with chronic reflux or surveillance of Barrett's is endoscopy, which involves inserting a long, flexible tube - fitted with a light and video camera on one end - through the mouth and down into the throat to examine and take biopsies from the esophagus and stomach.
But using endoscopy as an everyday screening tool for EA isn't prudent or really feasible, Dr. Shaheen argues. An estimated 40 percent of people have chronic heartburn, "and most will never go on to have Barrett's or certainly will never have cancer, so you'd literally be searching for a needle in a haystack," he says. "We do that in other areas of medicine, but we generally don't do it with a test that costs more than $1,000."
Dr. William J. Blot, of the Vanderbilt-Ingram Cancer Center, is leading an effort that he hopes might help identify candidates for regular EA surveillance. Much like the Gail model, which assesses breast cancer risk, he and his colleagues are developing a model that takes into account all of a person's risk factors and stratifies them into a low- or high-risk category for developing EA over a subsequent 5-year period.
There is not nearly as much data on EA risk factors as there is for a far more common cancer such as breast cancer, Dr. Blot says, so the new model would be less precise than the Gail model. "But," he adds, "it's a start."
By Carmen Phillips
Tumor Stem Cells May Improve Research on Brain Tumors
Researchers at NCI and the National Institute of Neurological Disorders and Stroke have found that glioblastoma tumor stem cells are a better model for studying the biology and physiology of glioblastomas than the cancer cell lines typically used in research laboratories. Tumor stem cells accurately reflect the biological mechanisms and genetic characteristics of the parent tumor, the researchers report in the May 15 Cancer Cell.
"This study illustrates that traditional cancer cell lines are a flawed model and poorly represent human tumors," said lead researcher Dr. Howard Fine, chief of NCI's Neuro-Oncology Branch. "We have shown that these tumor stem cell lines may ultimately offer a model system that more accurately represents the biology of the tumors actually found in patients."
His team grew glioblastoma tumor stem cell lines in two different culture conditions: one containing serum and the other serum free. The resulting stem cell lines were then compared with traditional glioblastoma cell lines grown in serum and with normal neural stem cell lines grown in serum-free solutions.
The investigators found that the glioblastoma stem cells grown under the two different conditions had very different physiological and genetic characteristics. The tumor stem cells grown under serum-free conditions had the same characteristics as the parent glioblastoma cells. The glioblastoma tumor stem cells cultured with serum, however, lost all biological and genetic characteristics of the original tumor cells.
Computerized Ordering of Chemo Drugs Slashes Error Risk
Use of a computerized system to order chemotherapy for pediatric cancer patients dramatically reduces the risk of potentially dangerous medication errors, according to a new study from Johns Hopkins University researchers.
To conduct the study, published in the May issue of Archives of Pediatric & Adolescent Medicine, the researchers conducted daily audits of sequential pediatric chemotherapy orders before and after the deployment of a new computerized provider order entry (CPOE) system in the Children's Center at Hopkins' Sidney Kimmel Comprehensive Cancer Center.
Compared with handwritten orders, use of the CPOE system resulted in a 74-percent reduction in improper dosing, a 91-percent reduction in incorrect dosing calculations, and a 68-percent reduction in missing cumulative dose calculations.
Multiple checks on medication orders by oncologists, pharmacists, and nurses are already in place, says lead author Dr. George R. Kim, so the chances of the errors getting through to patients are small.
Nevertheless, says co-author Dr. Allen Chen, dosing errors are potentially more harmful in children because, among other things, they absorb and metabolize drugs differently. "It's something that we worry a lot about in pediatrics because the dose range that's valid for one patient or another is enormous," he says.
Implementation of the CPOE system, the researchers cautioned, also introduced a new error: Medications were ordered that were not included in patients' approved treatment plans. The finding, Dr. Chen notes, reinforces the "importance of measuring the results of change and the need for careful monitoring when introducing a new system."
The results from the Hopkins trial, says Dr. Crystal Mackall, acting chief of the NCI Pediatric Oncology Branch, demonstrate that migrating clinical care processes - such as ordering medications - to a computer-based system with built-in decision support "should be a matter of high priority for improving the delivery of cancer care."
Rise in Thyroid Cancer Attributed to Better Detection
Data from NCI's Surveillance, Epidemiology, and End Results (SEER) program suggest that thyroid cancer in the United States increased by a factor of 2.4 between 1973 and 2002, rising from 3.6 to 8.7 cases per 100,000. Writing in the May 10 Journal of the American Medical Association, Drs. Louise Davis and H. Gilbert Welch of the Veterans Affairs Outcomes Group in White River Junction, Vt., conclude that "increased diagnostic scrutiny has caused an apparent increase in incidence of cancer rather than a real increase."
The authors found that papillary cancer (which accounts for 88 percent of all thyroid cancer) increased 2.9-fold, from 2.7 to 7.7 cases per 100,000, accounting for virtually all of the observed increase in overall incidence between 1973 and 2002. The increase was almost entirely attributable to small papillary cancers: Since 1988, 87 percent of the increase came from cancers 2 cm or smaller, and 49 percent from papillary thyroid microcarcinomas 1 cm or smaller. Improvements in technology made these smaller cancers increasingly likely to be detected; thyroid ultrasound can detect nodules as small as 0.2 cm, and fine-needle aspiration can immediately assess the cytology of the tissue. Since mortality remained constant throughout the 30-year period, the most likely conclusion is that these nodules were there all along, unobserved, underdiagnosed, and not progressing to death or even clinical disease.
In an accompanying editorial, Dr. Ernest L. Mazzaferri of the University of Florida agreed with the analysis, but warned that "some microcarcinomas are destined to become aggressive cancers," and cannot be ignored or relegated to watchful waiting on the basis of small size alone.
Researchers Identify Prostate Cancer Gene Variant
Researchers are reporting what they say is the first identification of a common genetic variant directly linked to the increased risk of prostate cancer. The variant, they reported early online May 7 in Nature Genetics, is more prevalent in African American men than in those of European ancestry, which, they note, may explain why African Americans are at higher risk of the disease.
Led by Dr. Kari Stefansson, of deCODE Genetics in Reykjavik, Iceland, the study included genetic analyses of participants in four case-control study groups from Iceland, Sweden, and the United States. They identified a genetic marker on chromosome 8, an allele of a microsatellite DG8S737, that increased risk in these different groups by more than 60 percent. The marker's presence yielded a "population attributable risk" - that is, the expected percentage of a given population whose cancer is attributed to the variant - of 8 percent in those of European ancestry and 16 percent in African Americans.
In the study, the researchers initially identified a suspect section on chromosome 8 in a study of Icelandic men with prostate cancer. They then performed genotyping on samples from participants in the four prostate cancer case-control studies to further determine if they could pinpoint a genetic variant linked to risk.
Compared with controls, the variant's frequency was significantly greater in prostate cancer patients with Gleason scores of 7 to 10. The variant's frequency also was greater in prostate cancer patients with higher Gleason scores than in those with lower Gleason scores, but only to a modest degree.
Studies of Energy Balance and Cancer in Humans
Announcement Number: PA-06-405
New Application Receipt Dates: June 1 and Oct. 1, 2006; Feb. 1, June 1, and Oct. 1, 2007; Feb. 1, June 1, and Oct. 1, 2008; Feb. 1, 2009.
This is a renewal of PA-04-124 and will use the R21 award mechanism. For more information, see http://cri.nci.nih.gov/4abst.cfm?initiativeparfa_id=3460. Inquiries: Dr. Virginia W. Hartmuller - firstname.lastname@example.com; Dr. Noreen M. Aziz - firstname.lastname@example.com; Dr. Sharon Ross - firstname.lastname@example.com
Cancer Surveillance Using Health Claims-Based Data
This is a renewal of PA-04-012 and will use the R01 award mechanism. For more information, see http://cri.nci.nih.gov/4abst.cfm?initiativeparfa_id=3452. Inquiries: Dr. Joan Warren - email@example.com
Cancer Surveillance Using Health Claims-Based Data
This is a renewal of PA-04-012 and will use the R21 award mechanism. For more information, see http://cri.nci.nih.gov/4abst.cfm?initiativeparfa_id=3453. Inquiries: Dr. Joan Warren - firstname.lastname@example.com
Adjuvant Treatment of Rectal Cancer
Name of the Trial
Principal Investigators
Why This Trial Is Important
To help prevent recurrence and improve survival, doctors are exploring the use of other treatments given either before (neoadjuvant) or after (adjuvant) surgery. In this trial, patients who were treated previously with neoadjuvant chemoradiotherapy (chemotherapy combined with radiation therapy) will be randomly assigned to receive adjuvant chemotherapy with or without the addition of the monoclonal antibody bevacizumab, which inhibits tumor blood vessel formation. Researchers will compare the overall survival of patients in the two treatment groups.
This trial is designed to accommodate patients who received neoadjuvant chemoradiotherapy as part of another clinical trial conducted by the National Surgical Adjuvant Breast and Bowel Project (NSABP-R-04).
"These two trials are intended to help define the best way to administer neoadjuvant and adjuvant treatment for rectal cancer," said Dr. Benson. "We hope to extend the benefits we have seen recently in adjuvant treatment for colon cancer to patients with rectal cancer."
Who Can Join This Trial
Study Sites and Contact Information
An archive of "Featured Clinical Trial" columns is available at http://cancer.gov/clinicaltrials/ft-all-featured-trials.
Dr. Paul Meltzer has been named chief, Genetics Branch, and head, Clinical Molecular Profiling Core at NCI's CCR. He joins CCR from the Cancer Genetics Branch of the National Human Genome Research Institute.
Dr. Meltzer is internationally recognized for his groundbreaking work on genes and mechanisms in cancer cell development. He and his colleagues advanced studies of gene expression profiles in cancer cells to better understand the progression and prognosis of cancers. By focusing on gene expression, gene amplification, and chromosomal abnormalities in various types of cancer cells, he is leading efforts to classify cancers, advance understanding of molecular events that mark cancer origin and progression, and identify novel therapeutic targets.
Dr. Meltzer earned his Ph.D. from the California Institute of Technology and M.D. from the University of Tennessee. He received postdoctoral training in genetics at the University of Cambridge and the University of Arizona, the latter at which he also completed his clinical training in pediatric hematology-oncology.
Body & Soul Mini-Symposium: Moving Research to Practice
Body & Soul is a faith-based, healthy living program developed by NCI-funded investigators for African American churches. The program provides congregations with strategies on how to include more fruits and vegetables as part of a healthy diet. It also teaches program leaders how to incorporate these messages into church gatherings, activities, and workshops.
At the symposium, key researchers presented the latest findings in cancer prevention and chronic disease behavior interventions - such as diet, physical activity, screening, and obesity - in faith-based channels, and discussed with practitioners the issues related to broadly disseminating the most effective findings in order to address and have an impact on important health issues.
To learn more about Body & Soul, or to order a free copy of the Body & Soul Program Guide, visit http://www.bodyandsoul.nih.gov.
This Week Is National Women's Health Week
NCI's Diet History Questionnaire Is Now Web Based
As an extension of the DHQ, NCI recently unveiled DHQ*Web, which is a Web-based questionnaire nearly identical in content to its hard-copy predecessor. DHQ*Web is a free research resource that takes advantage of the key aspects of automated and electronic questionnaires - respondents follow automated skip patterns, must complete all questions before proceeding, can navigate within the instrument to modify responses, and can log in at any time. DHQ*Web provides more efficient data quality because respondents cannot complete the questionnaire with missing or inconsistent responses.
For more information and a demonstration, go to http://riskfactor.cancer.gov/DHQ.
TREC Cancer Initiative Launches New Collaborative Relationships
The cancer research community faces a new challenge for the new century: the rising incidence of obesity worldwide and the suspected role that obesity plays in the development of many types of cancer. In response, NCI launched the Transdisciplinary Research on Energetics and Cancer (TREC) initiative to fund collaborative research - on how weight, diet, exercise, the environment, and other factors affect physiologic systems and intracellular pathways - to see whether and how they influence the development of cancer.
An essential component of the TREC initiative is the creation of a separately funded coordination center, located at the Fred Hutchinson Cancer Research Center, which promotes data sharing, evaluation, and collaboration among TREC investigators at four funded research centers, as well as with non-TREC investigators. Through this information hub, TREC is expanding opportunities for biospecimen banking, standardizing research methods across sites, and exploring ways to share data collection efforts at different centers.
In a traditional research framework, researchers at separate centers work independently and share their findings after all data has been gathered and analyzed. The TREC model ensures that data are pooled and progress is shared regularly so that research dollars are maximized and questions that will help guide public health efforts are answered in the shortest time possible.
"By creating the coordination center, we've not only capitalized on what worked well from earlier initiatives, but we're also looking at ways to improve our ability to develop transdisciplinary, trans-site partnerships," explains Dr. Linda Nebeling, chief of NCI's Health Promotion Research Branch of the Division of Cancer Control and Population Sciences. "We're bridging new transdisciplinary partnerships from areas of science that have not commonly worked together."
At a recent meeting on how best to integrate their research and maximize collaboration, TREC investigators found that respective programmatic goals could be leveraged to investigate a possible association between sleep disorders (sleep phenotype and gene-environment interactions) - which have been linked to obesity - and cancer. The TREC coordination center immediately helped organize a working group in this area, and research collaboration began. As research continues, the center will assist by providing collaborative study support for the development of common data elements and standardized measures, knowledge dissemination, network coordination, and evaluation.
The coordination center also assesses the overall effectiveness of the TREC research model. The center leads a unique evaluation research project, which includes a questionnaire to gather substantive evaluative data, in contrast to traditional self-reported measures. The data will be analyzed to measure the success of the individual centers, as well as the entire initiative.
"This evaluative effort looks at the productivity and impact of the TREC centers more extensively than has ever been done before for a large-scale transdisciplinary initiative," notes Dr. Nebeling. The evaluation results will have broader implications for NCI research models as a whole because the data will validate whether this type of transdisciplinary research mechanism is one that moves science forward.
"NCI is committed to developing better measures of team science processes and performance, and we hope to eventually use this information to inform decisions about the management of large initiatives such as TREC," says Dr. Nebeling.


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Advanced Blood Sugar Support (30 capsules, 30-day supply) | blood sugar supplements
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Cardiologist-developed formula for balanced blood sugar
and a healthy heart
It's well known that healthy blood sugar is critical to heart health. And it's balanced blood sugar that keeps your glucose numbers in line and your energy levels steady. But a little-known secret is that healthy blood sugar is also critical for fit blood vessels, robust circulation, well-functioning nerves, and more.
Exercising regularly and eating a fresh, natural diet with foods rich in antioxidants and healthy fats will go a long way to keep your waistline trim and your blood sugar balanced, but now there's a tool that can take your blood sugar management efforts to a whole new level. It's a breakthrough extract from French Maritime Pine Bark called Pycnogenol®.
Pure, powerful, patented Pycnogenol
Advanced scientific research has revealed that Pycnogenol has potent blood sugar benefits, including lowering fasting and post-meal glucose levels as well as promoting insulin sensitivity.
In one open label pilot study, 30 men and women with blood sugar concerns were given Pycnogenol in doses of 50, 100, and 200 mg, taking each for 3 weeks. Pycnogenol significantly lowered fasting and post meal blood glucose levels throughout the 9-week period, compared to baseline. Furthermore, insulin levels remained unchanged at all doses, indicating Pycnogenol facilitated blood sugar uptake by previously insulin resistant cells.
The Pycnogenol Difference
Pycnogenol is a patented pine bark extract from a select species of pine trees grown exclusively in Les Landes de Gascogne forest in Southwest France. This unspoiled forest has no traces of pesticides or herbicides and is therefore, exceptionally pure. The pine bark from these trees is also not subject to seasonal variations, which makes it an ideal botanical source.
The extraction process used on this pine bark adheres to rigorous quality standards, ensuring exact proportions of procyanidins, bioflavonoids, and organic acids. Pycnogenol is Kosher certified, Halal and "self-affirmed" GRAS 2.
Don't be fooled by Pycnogenol imposters! Other blood sugar formulas may use pine bark, but Pycnogenol is the ONLY pine bark extract shown in human clinical studies to have remarkable blood sugar and cardio benefits.
In another study—this one a double-blind, placebo-controlled trial—researchers evaluated the effect of 100 mg of Pycnogenol or placebo on fasting blood glucose in 77 subjects with blood sugar concerns. Pycnogenol was shown to significantly lower fasting blood glucose at every measurement through 12 weeks of treatment.
But Pycnogenol doesn't stop there
This remarkable nutrient has been shown in human clinical trials to support and even repair the delicate endothelial lining of blood vessels. It also aids in the production of endothelial nitric oxide, which helps to dilate blood vessels. This, in turn, promotes healthy blood pressure and circulation—even down to the body's tiniest arteries and veins.
Pycnogenol is the cornerstone of my one-of-a kind blood sugar formula
Advanced Blood Sugar Support combines research doses of Pycnogenol with proven blood sugar supporters like chromium and cinnamon, plus an advanced form of vitamin B1 called benfotiamine and alpha lipoic acid to address the TOP FOUR CONCERNS related to blood sugar control:
- Lowers both fasting and post-meal glucose levels with Pycnogenol.
- Promotes insulin sensitivity and minimizes harmful oxidized AGEs circulating in your bloodstream with two tried-and-true blood sugar control nutrients, cinnamon and chromium polynicotinate, plus the potent antioxidant alpha lipoic acid.
- Supports and repairs blood vessel endothelial lining with free-radical fighting power of Pycnogenol for healthier blood vessels and improved circulation, especially the microcirculation in your eyes, fingers, and toes.
- Soothes and comforts nerves with benfotiamine—a highly absorbable, fat-soluble form of vitamin B1—and other B vitamins shown in research to work in unison to improve sensory function.
LEARN MORE about the science behind these advanced ingredients.
Together, the nutrients in this hard-hitting supplement provide comprehensive support for anyone with blood sugar concerns (and if you're over age 60…that means YOU). Plus, these ingredients are all easy on your stomach, so you won't experience the digestive upset that's so common with other blood sugar formulas.
These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure, or prevent any disease.
Ingredients and Dosage
Doctor's Suggested Use: Take 1 capsule daily.
Serving Size: 1 Capsule
Servings Per Container: 30
|Amount Per Serving
|Vitamin B6 (as pyridoxine HCl)
|10 mg
|Vitamin B12 (as methylcobalamin)
|100 mcg
|Chromium (as polynicotinate)
|200 mcg
|300 mg
|Cinnamon Powder (bark)
|200 mg
|Alpha Lipoic Acid
|50 mg
|Pycnogenol®‡: French Maritime Pine Extract (bark)
|50 mg
|*Daily Value (DV) not established.
Other ingredients: Gelatin, magnesium stearate, silicon dioxide
Note: If you are taking blood sugar medications or are pregnant or lactating, consult a health care professional before taking this product.
Keep out of reach of children.
‡ Pycnogenol® is a registered trademark of Horphag Research Ltd, whose use may be protected by one or more patents.
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I always appreciate the professionalism from the Customer service Dept. They go the extra mile of seeing my health needs are met, seeing that I'm satisfied, and my patronage is highly appreciated...
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My blood sugar was tested by my Dr. and it was lower after 2 weeks. She said good I didn't need to go on anything.
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I love this product it really worked for me I will definetly continue this product. My rate is 100.
See why Dr. Sinatra partners with Healthy Directions
Science Behind the Ingredients
Pycnogenol is a standardized extract from French Maritime Pine Bark and consists of powerful antioxidants phenolic compounds, including catechin, taxifolin, procyanidins, and phenolic acids. It is the ONLY pine bark extract shown in human clinical studies to have significant blood sugar and heart health benefits.
In one open label pilot study, 30 men and women with blood sugar concerns were given Pycnogenol in doses of 50, 100, and 200 mg, taking each for 3 weeks. Pycnogenol significantly lowered blood glucose levels throughout the 9-week period, compared to baseline. Furthermore, insulin levels remained unchanged at all doses, indicating Pycnogenol facilitated blood sugar uptake by previously insulin resistant cells.
In another study—this one a double-blind, placebo-controlled trial—researchers evaluated the effect of 100 mg of Pycnogenol or placebo on fasting blood glucose in 77 subjects with blood sugar concerns. Pycnogenol was shown to significantly lower fasting blood glucose at every measurement through 12 weeks of treatment.
Pycnogenol is a powerful phenolic antioxidant that also supports blood vessel health and strong circulation. In the endothelium of the blood vessels, Pycnogenol stimulates the enzyme that produces nitric oxide (NO) in the body. This, in turn, stimulates blood vessel dilation and increased blood flow throughout the body with benefits for the entire cardiovascular system, especially areas of microcirculation, such as blood vessels in the eyes, fingers, and toes.
Nishioka K, et al. Pycnogenol, French maritime pine bark extract, augments endothelium-dependent vasodilation in humans. 2007.
This is a unique fat-soluble form of vitamin B1 and is found in roasted crushed garlic and other vegetables, such as onions, shallots, and leeks. Benfotiamine's unique open-ringed structure allows it to cross easily through the intestinal wall and pass directly into cells.
It is believed that this vitamin can inactivate harmful AGEs, which disturb nerve function and comfort. Clinical studies of benfotiamine, along with vitamins B6 and B12, have shown that this nutrient trio soothes and comforts nerves and supports healthy sensory function.
Winkler G., et al. Effectiveness of different benfotiamine dosage regimens. Arzneim-Forsh/Drug Res 1999; 49(1): 220–24.
Simeonov S., et al. Folia Medica 1997;39(4):5–10.
Haupt E., et al. Int J Clin Pharmacol Ther 2005; 43(2):71–7.
Cinnamon Powder (Bark)
This extract from the bark of a small Southeast Asian evergreen tree has been used in traditional Chinese medicine for thousands of years. Cellular research indicates that cinnamon's active ingredient (MHCP) may help activate insulin receptors and work synergistically with insulin to stimulate glucose uptake and glycogen synthesis.
Jarvill-Taylor, K. JACN. 2001.; 20(4): 327–36.
Alpha Lipoic Acid (ALA)
This powerful, naturally-occurring nutrient is an important activator for enzymes that drive cellular mitochondrial engines, but levels decrease with age and as a result of certain health conditions. ALA is an extremely potent antioxidant that helps terminate free radicals and regenerate other antioxidants, which is important in reducing the oxidative stress associated with excess insulin.
Packer L., et al. Alpha Lipoic Acid as a biological antioxidant. Free Radic Biol Med 1995 19(2): 227–50.
This essential trace element is required for normal fat and carbohydrate metabolism and healthy glucose tolerance. Chromium may help promote insulin sensitivity by increasing the number of insulin-binding sites on cells, which allow for better transport of glucose into cells for energy.
Wilson, B. Effects of chromium supplementation on fasting insulin levels and lipid parameters in healthy, non-obese young subjects. Diabt and Clin Prac. 1995(28): 179–84.
Anderson, RA. Effects of chromium on body composition and weight loss. Nutrition Review 1998. Sep:56(9) 266–70.
Anderson, RA. Chromium supplementation on human subjects: Effects on glucose, insulin, and lipid variables. Metabolism. 1983;32(9): 894–99.
Product Quality
- Manufactured to exacting standards using highest quality raw materials
- Produced under our own SOPs that meet or exceed FDA GMPs
- Every batch tested to verify purity and potency
- Specific product testing is listed in the Certificate of Quality
- Quality assured with our Triple Testing Philosophy™
- Backed by our 100% satisfaction guarantee
Frequently Asked Questions
How do I know I am choosing the best supplements?
Are there any known supplement/drug interactions?
If you are taking a blood sugar medication, or are pregnant or lactating, consult a healthcare provider before taking this product. If in doubt, consult with your physician before taking this or any drug or natural supplement. This supplement is not intended for children
Are there any side effects?
There are no known major side effects of Advanced Blood Sugar Support.
Are there any allergens in the product?
This product does not contain any of the major allergens, including soy, wheat, milk, egg, peanuts, nuts, fish, or shellfish.
How much should I take?
I advise anyone who wants to support optimal blood sugar levels to take 1 capsule of Advanced Blood Sugar Support daily. Because the body's normal blood sugar control mechanisms become less efficient with age, I suggest that everyone over age 60 add this supplement to their daily regimen.
If you have serious blood sugar concerns, you can take up to 3 capsules daily. Clinical research shows that, at this dosage level, the Pycnogenol in Advanced Blood Sugar Support can support blood sugar health over time.
1 Liu X et al. French Maritime Pine Bark extract Pycnogenol dose-dependently lowers glucose. D.Care 2004;27(3):839.

subset: commoncrawl


text:
(based on 117 reviews)
Ratings Distribution
5 Stars
4 Stars
3 Stars
2 Stars
1 Stars
of respondents would recommend this to a friend.
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Most Liked Positive Review
We started using Case ...
We started using Case Logic DVD notebooks to store our DVDs several years ago. Until recently, we were very pleased with the design. The new design with the two band Quick Lock system...Read complete review
We started using Case Logic DVD notebooks to store our DVDs several years ago. Until recently, we were very pleased with the design. The new design with the two band Quick Lock system is not very user friendly. If you want to keep your DVDs in a particular order, you have to remove several DVDs to put the new page in. The 3 ring binder design was much better. Now we scour EBay and other vendors to find the old 3 ring design. We also preferred the all black Koskin look vs the saddle stitch in the new design.
Most Liked Negative Review
The opposite of convenient!
When the Case Logic 3-ring DVD case with single pages came out in the 90s, it was the best product of its kind, and still is. When they switched to the...Read complete review
When the Case Logic 3-ring DVD case with single pages came out in the 90s, it was the best product of its kind, and still is. When they switched to the DVB-40 and eliminated the 3 rings and went to the plastic flap, they changed a useful product into something that is almost useless for my purposes. I am always adding to my collection, and I remove a sleeve with the movie when I watch one. Both of these things are almost impossible with that ridiculous flap that you have to thread through EVERY sleeve! If they would re-release the 3-ring single-sleeve binder, they would sell so much more!
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kudos to case logic
By bj
from alpine, ca
before this last order, i had already owned 25 of these, both the large and the 48 disc size. i always get complaiments on how covenient and good looking they are. the dvds are protected, and yet readily available for veiwing. thanks CASE LOGIC for not being head blind to the needs of a dvd addict.
Bottom Line Yes, I would recommend this to a friend
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Great product, looks great on the shelf.
By PJ
from Bellingham, WA
Over the years I've bought 12 of these binders and I hope they keep making them, because I might need more.
I would buy this product over and over
By Mishu
from Boise, Idaho
Delivery was quick. Website user friendly
Great way to consolidate bulky movies.
By Organizing Mom who needed space
from Midland, TX
We recently decided to store all of our DVDs somewhere other than in those bulky, space consuming racks. Case Logic was the first place I looked and these DVD storage cases are the best. Easy to use and to store. We love them.
(1 of 1 customers found this review helpful)
Disappointed with the sleeves
By Tom
from Scottsdale, AZ
Store film collection
Bottom Line No, I would not recommend this to a friend
By Scooter
from Boise, ID
Where are the refill pages!
By RPV MOM
from Los Angeles, CA
I like the DVD cover slot, and the backside of the page has two slots for an extra's DVD and the movie if you have a 2 disc set or like some DVD's sold now have a regular DVD and a BlueRay disc. I can't figure out how to open the binder thing; It does not come with instructions. Where to find refill pages?! There is room for adding more pages to the case but no where to buy refills. I like this case but I do need to buy another DVD case but I will have to look for another brand that has refill pages to purchase. I would give it 5 stars if there are refill pages. I would only recommend if you don't care about refill pages.
Great for DVD collection!
By Tania
from Nebraska
I love the fact that I can consolidate my entire DVD collection into about 5 cases, however, there is still plenty of room to add more, but I cannot find the sleeves sold seperately for this album. In regards to the cover art, one only needs to cut out the spine and then the front and back pieces slide in nicely.
(4 of 17 customers found this review helpful)
I love this DVD Album! It ...
By KARRIE
from Bellevue, WA
I love this DVD Album! It fits the case and the dvd's and hold a lot of them.
(7 of 13 customers found this review helpful)
I really like the ability ...
By MICHELLE
I really like the ability to reduce the space that all my DVD's are kept in as well as the fact that I can keep them organized. I can organize them as I want and then when we travel just grab them and go without creating a mess later.
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We have noticed that members of the Anonymous movement have expressed their concern on the research project INDECT (Intelligent information system supporting observation, searching and detection for security of citizens in urban environment).
INDECT is a the Framework Programme 7 for Research and Innovation (FP7) security research project that tries to develop a mechanism to swiftly and automatically analyse the footage of video surveillance cameras. This means that INDECT is developing tools which will enable police forces to automatically analyse video images.
Anonymous is calling in a recently posted You Tube clip for a protest against INDECT on the 28th July 2012.
We would like to inform the authors of this clip that they are cordially invited to an open discussion with the Commission on INDECT.


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The Webster Extension Service is happy to announce that we have a new assistant county agent who will be working with Agriculture and Natural Resources and 4-H Livestock programs.
Lee Faulk, a native of Athens is married to Ramsay Magee Faulk, who is an occupational therapist with the Claiborne and Bienville School Systems. Lee has a degree in Ag. Business from La. Tech and has worked for the LSU AgCenter for four years. He is currently working in both Claiborne and Webster Parishes with ANR and 4-H.


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I'm only 7 DPO today so the fact that I definitely see *something* where the test line should be threw me off. Do you see anything? It's hard to tell on the picture, I did the best I could with my camera though
I'm only 7 DPO today so the fact that I definitely see *something* where the test line should be threw me off. Do you see anything? It's hard to tell on the picture, I did the best I could with my camera though
It is really early but you know, I do see something and it looks pink on my screen...not grayish like an evap...oh Karen I reeeeeally hope that's a faint bfp !!!!
I'm containing my excitement for now lol, can't wait to see tomorrow's test !!!
Have you put it on countdowntopregnancy.com? The tools sometimes help bring it more.
Last edited by kellyowens; 02-23-2013 at 02:05 PM. Reason: spelling
I made an account there Kelly! Here's another picture I just took
And here's the invert, I definitely see something on the invert where I see the line IRL
I see a possible line on the 2nd pic.
Definitely a line on the invert and I don't think evaps show when inverted...okay cannot contain any longer !! Sure looks like the real deal to me !!!!!
Eeeek! it gets darker!!!
Looks like something to me! Like a
Maybe you Od earlier that you thought?
I'm pretty positive I O'd on CD 12, that's when I had spotting! But it's possibly I O'd on CD 11. Ahhh can't wait to test tomorrow!!
I see something too!
Cait[24] & Gene-Paul[28] Dx with PCOS & Left Tube Blocked Dec. '12
Sean Patrick born 3/11/14, 7lbs 13oz
**Stalker here** I normally don't see them but I do see a line!! I hope this is it for you!!! Fingers crossed and baby dust!!!
Thank you guys! I'm anxious about tomorrow!!
I see it too!!! How exciting!!!!
Ok, it's almost 6am...where's this mornings test
...stalking ...lol, no pressure though
Sorry guys I'm on the west coast and I am just getting around to my online stuff! Definitely a second line on this morning's test but it's a little more faint than yesterday's. I'll keep testing everyday! I'm more annoyed that my BBT disappeared from my end table so I couldn't temp this morning!
We need pics!!
I only took one with my phone and accidentally scratched the test so it looks all jacked up.
I would love a boy since we're done after two but I would love a girl just the same
Why can't I see the pics to your test? I wanna see too!!!
I'm not sure Cindy! PM me on Facebook or something and I'll send them to you. I showed DF the test and he saw the second line. He said "nah you can't be pregnant, if you were that would be a lot darker". I suppose time will tell.
Stalking. Ummm. I totally see it!!


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It's getting to be that time of the year... your best chance at bagging a monster buck. Why? They're out looking for 'action'.
Since white tail deer breed during a select few weeks throughout the year, the periods tend to bring the big boys out during the day, and into areas where you may not have seen them before. They are cruising scrape lines, making rubs, grunting, fighting, and trying to pair up with a hot doe. These big bucks will move heaven and earth to 'hook up', and that means they throw caution to the wind.
That's your cue to get in the woods as much as possible.
Let's talk about determining when the rut is going to happen:
One long-held idea is that the rut happens during the 10 days surrounding the second full moon after the Autumnal Equinox. This year's equinox happened on September 22, so that would place the rut somewhere in the vicinity of 11/13 and 11/23, give or take a couple of days.
The other school of thought is that the rut is triggered by the weather. Once you start getting cold snaps in your area (where temps fall down into the 20's and 30's at night, and stay in the low 40's during the day), it sparks the deer to get moving... and to get busy.
Now, I've found them both to be somewhat accurate, in fact, I typically judge the rut based on Halloween. From Halloween to mid-November, I try to be in my stand as much as possible because that's when I tend to see chasing and lots of deer movement.
Quick tips for hunting the rut:
1. Use scents and calls to up your game: I've found rattling during the pre-rut to be super effective, just make sure you start lightly. Bucks are just testing each other right now, so no need to rattle a war. Keep it simple. I've successfully turned bucks around using a grunt, but like rattling, don't overdo it right now or you could spook your trophy. If you do grunt, do something light and short, hang onto the aggressive calling for a couple of weeks until you know the boys are in full-on rut. Bottom line: use them sparingly, no need to constantly call or rattle, it'll do more harm than good.
2. Check for scrape lines: look for trails with scrapes along them, especially spots with multiple scraps and licking branches in a small area, that typically is a sign that you are in a buck's home territory. Those areas are where you want to be, as bucks will be cruising by to check those scrapes.
3. Look for the does: you've likely been bow hunting for several weeks, where are you seeing the does? Follow the does and you'll find the bucks.
4. Get out and hunt: it's like the lottery, you can't win if you don't play. Try hunting during the midday. Bucks won't care that it's 11am, if they're cruising for does, time is a non-factor. Get into the woods as much as possible, but try to mix it up. The last thing you want is to do is get patterned.


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The U.S. may be on it's own when it comes to military action against Syria.
The British Parliament voted against backing a strike. Other allies including Germany have said they're not going to get involved and France wants to wait until U.N. Inspectors finish their investigation into the possible use of chemical weapons.
Right now, five U.S. destroyers are near the coast of Syria in preparation for a possible attack.
As the U.S. considers taking action against Syria, protests are taking place across the country urging the U.S. not to get involved in the crisis.
Fox 2's Roop Raj spoke to one man about the possibility of another battle in the Middle East.
Dr. Yahya Basha has lost cousins at the hands of the Assad regime in Syria. Even though he's been in the U.S. for 40 years, he is saddened by recent reports the Syrian government used chemical weapons on its own people.
"The people want a journey to democracy, prosperity to education and science to a decent living," says Basha.
The Obama administration has been steadfast in its stance to take on Syria although a timeline is unclear. The possibility of war in the Middle East is frightening.
Basha says widows and orphans are now the latest victims of the chemical attacks. He says would welcome intervention but it would have to be an effective change not just symbolic.
He adds, "It needs to be serious to get people to sit at the table and negotiate."


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Concert promoters created handbill versions of many of their posters and used them as sidewalk handouts and dashboard fliers to promote upcoming shows. Many of the handbills are double-sided, with poster art on one side and a calendar of upcoming shows on the other. These handbills represent an important element of rock concert history because they were hands-on marketing tools that united promoter and patron.
John Staehely


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Experts you can trust - All of our technicians are ASE certified. We are in good standing with the Better Business Bureau (BBB-Tulsa) with no complaints on file. Ask our customers and you'll see that we do our best to give ...
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Fast repair - RC was able to diagnose, get the parts, and fix my car in 1 day without an appointment - I dropped off the car and used the key drop. I am very pleased with their service and speed. Tripp is very good...
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Amazing! - I sent my old 928 in for work. He had it done in a few days and ran better than when I first got it! Great job Tom!
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The best for Fords. - He knows what he is doing you just got to be patient with him he works by himself. Excellent Quality and good workmanship. He is also good for harcore racing applications.
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Christmas was getting to be a challenge for one Detroit family. They have a two-year-old child on a ventilator, bed bugs and now the mother is in the hospital. But complete strangers have stepped up and are delivering a holiday miracle to this family. It was a humbling moment Monday for the movers with Got Donations and Humble Designs in Detroit when they stepped foot into the Hoskins' home. "When I walked in that house that first thing I did was look ... and I said, 'Where's the ornaments? Where's the presents?'" remembers Rob Rothenberg, a Got Donations mover. What he saw was a bare tree and empty rooms in the new home of the Hoskins family. Their old house became too dangerous for two-year-old Shayla when a storm knocked out their power."[Shayla] was born with a condition called Hydrocephalus - you have too much fluid in your brain. She's been through a lot," says Shayla's nurse, Krystal Howard. She says Shayla was also born prematurely and doctors were not sure if she was going to survive. "These machines, they do work when the power is out but they only work for so many hours," explains Howard. "It's kind of rough sometimes but our family always pulls through. We're kind of like a wolf pack. We never leave anybody behind," says Aubrie Hoskins. 12-year-old Aubrie and 13-year-old Andreya act very grown up, along with their four brothers and sisters, to help Shayla. They call her an inspiration.After their mother called Fox 2, we talked to the folks at the DO Foundation who reached out to The Auction Block to team up with Got Donations and Humble Design to bring furniture to this empty home.VIDEO: Click on the video player above to hear more from the family and movers in a report from Fox 2's Erika EricksonAfter realizing just how much the Hoskins need this Christmas the folks with Humble Design are getting ornaments, toys and even a new crib for Shayla.
If you would like to donate to the Hoskins family you can do so at www.dofoundation.net/hoskins.
205 N. Michigan AvenueGround FloorChicago, IL 60601Station Operator: (312) 565-5532Newsroom: (312)565-5533


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Enticed by federal Race to the Top dollars, Massachusetts passed an important education reform law in 2010. But now, with that legislation in place, policymakers seem to lack the appetite for another round of significant change.
Take Governor Patrick, for example. He's using the prospect of increased education spending to try to leverage a big tax hike, but hasn't called for any important new reforms to the K-12 system. Nor has he displayed any interest in another charter school cap lift.


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Super Monday Night Combat Preview
"So, Monday Night Combat is coming to the Super Nintendo. Seems weird," I joke as I'm shuffled into a back room with two Uber Entertainment developers. It takes a moment, but they both start to laugh. "Yeah. You got it," executive producer Chandana Ekanayake replies. "We think it will work," shoots creative director John Comes.
What Super Monday Night Combat actually is, however, is something reminiscent to the original game in the series, with a major twist: it's a PC-exclusive, free to play (F2P) affair. Had the PC version captured so much attention that going F2P was the next logical step?
"The [Xbox] 360 version actually did better than the PC," Ekanayake admits. "It [the PC version] did about two-thirds of what the Xbox did." So, why has Uber decided to make the shift, I wonder?
"We want it to be on the Xbox, obviously," Comes tells me. While Free-to-Play titles have exploded on the PC and Mac, consoles have yet to delve into the market with much success.
"When we were doing the Steam version, we were doing a bunch of updates. We kind of liked that. It fits with how we like to develop," Ekanayake says. It's not the first time I've heard this. PC and Mac platforms are so open that developers are free to make updates as they see fit; whereas making updates on a console requires certification from platform holders. It's possible, but developers don't have nearly the same amount of control. There's instant feedback on PC, something Ekanayake admits Uber Entertainment "loves."
Super Monday Night Combat takes from the original game, adds and removes elements, and attempts to balance it all before launching.
The original classes define the roles of new characters in Super Monday Night Combat. Characters from the original game return, fitting into character roles. Commandos include debuffers, closers, utility characters like the Assassin; Strikers are jack-of-all-trades, high mobility characters like the Assault; Enforcers have high health, are slow moving, and hit for high short-range damage like the Tank, Veteran, and Gunner; Defenders are buffers, area holding, and healing characters like Support and Combat Girl; and Sharp Shooters have high aim skill, deal burst damage, traits of the Sniper and Gunslinger. Some of the original skills have been removed and some new ones have been put in the pair tell me, not willing to go into too much detail.
"Some of the big gameplay changes are that you actually level up playing the game," Comes says. This persistent player level system is new, versus the skill leveling system from the first that continues in Super Monday Night Combat. There are now five skill levels.
Damage has also decreased throughout the game, which Uber says they hope will allow for longer matches where players can take advantage of more of their preferred skills. In the first game, things ended too quickly and some players rarely had time to use top-tier skills. "You get a sense that from the beginning of the game until you get to the end of the game you're much stronger," Comes tells me.
Another change is the elimination of overtime, which Comes admits was met with "mixed reviews." Its original intention was to "end the game at a certain point," but it didn't work.
"We've changed the way that bot waves work and turret waves work so that the game naturally comes to an end somewhere around twenty-ish minutes," Comes explains. "Some will go longer, some will go shorter. You do get this more organic game now." Crossfire mode has been reduced to five-on-five, versus six on each side in MNC. Uber hopes the change will make strategy more of a consideration as there are now an uneven amount of players protecting a map's various lanes of attack.
The game's style itself looks essentially the same as the original; however, environments have expanded out of arenas and into more organic-looking battlefields. The core of the game, however, remains the same. It's all about the money ball.
"One thing we talked about internally is that we don't want to gate the player," Ekanayake says. "We want the player to have a full game experience. We want a player to play as much as they want but not have to spend money on it." But where is the money coming from?
"We'll have certain free characters on a weekly basis or bi-weekly basis that you can try out. If you like that character and want to keep that character, then you can buy them." The system sounds similar to the structure of League of Legends, which Uber agrees is a fair comparison. In order to maintain balance, Uber will offer several characters to for users to play as for free.
"We've expanded Endorsements, you now get twenty-five instead of three," Comes explains. "We've introduced Products, which are kind of like items in the game. Endorsements just improve your states whereas Products change the gameplay."
The example Comes outlines is one product that drops a bomb near your corpse when you're killed that explodes a few seconds after you're downed. Both Endorsements and Products can be earned by playing the game or purchased for real-world money. "The vast majority of things you can buy, you can also earn in the game." There are two currencies in the game: Combat Credits, which act as in-game cash and Uber Points, which players can purchase.
Right now, Uber Entertainment says the game is coming "this winter," but won't solidify whether that means late 2011 or early 2012.
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We are the main academic organisation in Britain for people interested in all aspects of the Renaissance.
Re-live your conference experiences with our selection of the best tweets!
The University of Southampton's Centre for Medieval and Renaissance Culture hosted the 6th Biennial SRS Conference on the theme of 'Performative Spaces' between 12th and 15th July 2014.
This special issue, Women and Healthcare in Early Modern Europe (Vol. 28, no. 4, September 2014; Guest editor: Sharon T. Strocchia), brings fresh interpretive perspectives and impressive archival research to bear on the reappraisal of women's medical activities in early modern Europe.
The 2014 SRS book prize was awarded to Alec Ryrie for his book, Being Protestant in Reformation Britain (OUP, 2013). Two other books were highly commended, Guido Alfani, Calamaties and the Economy in Renaissance Italy: The Grand Tour of the Horsemen of the Apocalypse, trans. Christine Calvert (Palgrave, 2013), and Sharon Gregory, Vasari and the Renaissance Print (Ashgate, 2012).
University of Kent.
The Fellowships Committee is pleased to announce Holly James-Maddocks as the winner of this year's Postdoctoral Fellowships competition (2014-15). Three new Study Fellowships were also awarded.
TORCH, University of Oxford.
Joanna Craigwood discusses a recently-discovered holograph text of a poem by Matthew Prior.
St John's College, Cambridge.
The latest issue of Renaissance Studies (Vol 28, no. 3, June 2014) is now available on-line via the Wiley-Blackwell website.
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Rated 4.8 out of 5Â by 10 reviewers.
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Rated 5 out of 5Â by JRAja Just what we wanted I ordered these for my wife as she has a small but wide foot. They were exactly the correct size. Delivery was fast as they arrived within a few days. Will oder again when she or I need other styles. 9/9/14
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1-10 of 10


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I take it he's not a fan of the tub...
YouTube Description: Dog plays dead to avoid bath time - Here this funny dog plays cheeky to not to take a bath.
Desperate times call for desperate measures. :)
Any of your pets go to such great lengths to avoid bathing?


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Long Island Sportscast, July 3
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September 17, 2014
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MARRIAGE DIGEST: With military policy reversed, gay couples want family benefits
Posted on Sep 23, 2011 | by Staff
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WASHINGTON (BP) -- With the military's Don't Ask, Don't Tell policy now repealed, supporters of open homosexuality in the military are targeting another law -- the 1996 Defense of Marriage Act -- and pushing the Department of Defense to do more in accommodating same-sex couples.
DOMA, as it is often called, defines marriage as between a man and a woman for federal purposes and gives states the option of not recognizing another state's gay "marriages."
Some supporters of marriage redefinition hope the repeal of Don't Ask, Don't Tell will strengthen the legal case against DOMA. But even if it doesn't, the new military policy certainly will result in squabbles over what the military can and can't do when it comes to gay couples.
Aubrey Sarvis, the executive director of the Servicemembers Legal Defense Network -- which worked to overturn Don't Ask, Don't Tell -- sent a letter to Secretary of Defense Leon Panetta Aug. 11, urging the secretary to open the military's various family benefits to same-sex couples.
"There is more that you can do to bring about a military that is both open and equitable," Sarvis wrote.
"With the repeal of 'Don't Ask, Don't Tell', there will be two classes of service members in the U.S. military -- those who receive full family support, pay and benefits and those who do not," Sarvis wrote. "We fully understand that the Defense of Marriage Act prevents the Department from extending the same support and benefits to all service members. However, you have the ability, within the confines of that law, to make same-sex married couples and their families eligible to take part in some of the same programs that are available to straight married couples and their families. These include making same-sex married couples eligible for joint duty assignments, family center programs and military family housing."
Supporters of DOMA say the 1996 law prevents same-sex couples from receiving military family benefits.
Conservatives are concerned the military's new openness will not only weaken the definition of marriage and the family but also will restrict religious freedoms and while infringing on personal privacy.
Already this year, congressional lawmakers had to step in after a Navy memo declared that same-sex "weddings" could occur at chapels in states that recognize gay "marriage." The Navy reversed course but left open the possibility it could change again.
"President Obama made a political promise to LGBT activists, and Defense Department appointees have created a shaky house of cards that is about to collapse," said Elaine Donnelly, president of the Center for Military Readiness.
U.S. CATHOLIC LEADER WARNS OBAMA ON MARRIAGE -- The president of the U.S. Conference of Catholic Bishops sent a strongly worded letter to President Obama Sept. 20, urging him to "push the reset button" on his opposition to the Defense of Marriage Act and warning the president that a clash between church and state is looming if marriage is redefined. In February, Obama ordered the Justice Department to stop defending DOMA in court. Since then, though, the Justice Department has gone from being neutral to actually opposing DOMA.
The letter could signal more involvement by Catholic leaders in the 2012 presidential race.
"I urge yet again that your Administration end its campaign against DOMA, the institution of marriage it protects, and religious freedom," wrote Timothy M. Dolan, archbishop of New York and president of the U.S. conference.
Dolan said the Obama administration's opposition to DOMA in court has given Dolan a "growing sense of urgency" to write and express his concerns. Legal language equating opposition to marriage redefinition with racism is "especially wrong and unfair," Dolan said.
"Mr. President, I respectfully urge you to push the reset button on your Administration's approach to DOMA," Dolan wrote. "Our federal government should not be presuming ill intent or moral blindness on the part of the overwhelming majority of its citizens, millions of whom have gone to the polls to directly support DOMAs in their states and have thereby endorsed marriage as the union of man and woman. Nor should a policy disagreement over the meaning of marriage be treated by federal officials as a federal offense -- but this will happen if the Justice Department's latest constitutional theory prevails in court. The Administration's failure to change course on this matter will, as the attached analysis indicates, precipitate a national conflict between Church and State of enormous proportions and to the detriment of both institutions."
Dolan added, "We as Bishops of the Catholic Church recognize the immeasurable personal dignity and equal worth of all individuals, including those with same-sex attraction, and we reject all hatred and unjust treatment against any person. Our profound regard for marriage as the complementary and fruitful union of a man and a woman does not negate our concern for the well-being of all people but reinforces it. While all persons merit our full respect, no other relationships provide for the common good what marriage between husband and wife provides. The law should reflect this reality."
Michael Foust is associate editor of Baptist Press. With reporting by World News Service.
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Former NFL star and current Fox Sports analyst Howie Long and former NFL star Michael Strahan joined other celebrities to film a PSA about bullying.
"One of the things we pointed out in the PSA today, one in every four kids is bullied in school," Long said. "That's pretty startling."
Strahan said it's a topic near to his heart because he was bullied as a kid.
"Look at the gap in my teeth -- you think this was easy to grow up with?" Stahan said. "A lot of talk about that. Even at home, with my brothers. You look at it as just part of growing up, but it shaped me and defined me."
The idea for the PSA came from an organization called Stomp Out Bullying. Elena Brown, 14, a relative of a Fox 5 employee, works as an ambassador for the organization.
"Everybody knows somebody who has been bullied and if you don't stand up, then you're not helping," Elena said. "So it's very important to stand up and say something."
Another teen ambassador, Alex Levy, said: "I personally was bullied, when I was in elementary school and it really affected me. So if we can get this message out and help more and more people, it's a really good thing."
The PSA will air on Fox Sports.


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MA Management Consulting
Ron is currently a senior partner at the IXL Center and at the Spinnaker Group (a venture capital firm). He is on the Faculty of the Hult International Business School, and on the Advisory board of Arthur D. Little Inc. (ADL). He was most recently a senior partner of the Monitor Group where he founded and led their Innovation practice and was founder of IMI (Innovation Management Inc.). For 20 years he was the managing director of the Technology and Innovation Management Practice for Arthur D. Little worldwide. He was also Chief Innovation Officer and served on their Technology Investment Board and Management Education Institute Board.


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42 U.S. Code § 5677 - Limitations on use of funds
Source(Pub. L. 93–415, title II, § 299F, as added Pub. L. 107–273, div. C, title II, § 12216,Nov. 2, 2002, 116 Stat. 1893.)
Effective Date
Section effective on the first day of the first fiscal year that begins after Nov. 2, 2002, and applicable only with respect to fiscal years beginning on or after the first day of the first fiscal year that begins after Nov. 2, 2002, see section 12223 ofPub. L. 107–273, as amended, set out as an Effective Date of 2002 Amendment note under section 5601 of this title.
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