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Oral Contraceptives Reduce Long-Term Risk of Ovarian Cancer
Since they were first licensed nearly 50 years ago, birth control pills containing estrogen have prevented some 200,000 cases of ovarian cancer world-wide, estimate the authors of a study published January 26 in The Lancet. Further, in the absence of having taken oral contraceptives, half of these women would have died of the disease.
The researchers showed that oral contraceptives (OCs) continue to confer protection for years - even decades - after women stop using them. Thus, they surmise, "the number of ovarian cancers prevented [will] rise over the next few decades" to at least 30,000 each year. Read more
Sorafenib Increases Risk of High Blood Pressure
A meta-analysis published online January 24 in Lancet Oncology reports that patients receiving the standard clinical dose of sorafenib (Nexavar), an anticancer drug that targets the growth of tumor blood vessels, or angiogenesis, have a significantly increased incidence of hypertension.
Previous studies have found an increased risk of hypertension with the use of other targeted drugs and antiangiogenesis agents, including sunitinib (Sutent). To see if sorafenib also increases this risk, and subsequent risk of heart attacks and other serious cardiac events, the authors combined clinical trials data from three published papers and six meeting abstracts that included data on hypertension for patients assigned a starting dose of 400 mg of sorafenib twice daily, which is the current starting dosage approved by the FDA. Read more
Oral Contraceptives Reduce Long-Term Risk of Ovarian Cancer
Since they were first licensed nearly 50 years ago, birth control pills containing estrogen have prevented some 200,000 cases of ovarian cancer world-wide, estimate the authors of a study published January 26 in The Lancet. Further, in the absence of having taken oral contraceptives, half of these women would have died of the disease.
The researchers showed that oral contraceptives (OCs) continue to confer protection for years - even decades - after women stop using them. Thus, they surmise, "the number of ovarian cancers prevented [will] rise over the next few decades" to at least 30,000 each year.
These figures emerge from a comprehensive meta-analysis based on prospective and case-control data from 45 epidemiological studies in 21 countries, mostly in Europe and the United States. "These findings set a new standard in prevention for a deadly cancer," wrote the editors of The Lancet, "and have important public health implications."
The results showed that women who had ever taken OCs were 27 percent less likely to develop ovarian cancer. The studies included 23,257 women with ovarian cancer, 31 percent of whom had taken OCs; of the 87,303 controls, 37 percent took OCs.
Two trends emerged that were really striking, according to Dr. Beth Karlan, editor-in-chief of Gynecologic Oncology and director of the Gilda Radner Cancer Detection Program at Cedars-Sinai Outpatient Cancer Center in Los Angeles. First, the longer OCs were used, the greater the ovarian cancer risk reduction, decreasing about 20 percent for each 5 years of use.
The second clear trend was the duration of the protective effects, which lasted long after women had stopped using OCs. For each 5 years of use, risk of developing ovarian cancer was reduced 29 percent in the first 10 years after stopping. The risk reduction was still significant though smaller (19 percent) for years 10–20, and smaller still (15 percent) 20–29 years after discontinuation.
Another feature of these results is their uniformity. OCs seem to protect against nearly all types of epithelial and nonepithelial tumors, with the possible exception of mucinous ovarian cancer (which accounted for only 12 percent of cases studied in the meta-analysis). The Lancet editorial points out that the results show "the benefits of oral contraceptives are independent of the preparation [estrogen dose], and vary little by ethnic origin, parity, family history of breast cancer, body-mass index, and use of hormone replacement therapy."
Representatives from nearly all of these studies - including Drs. Patricia Hartge, James Lacey, Louise Brinton, and Robert Hoover from the Epidemiology and Biostatistics Program in NCI's Division of Cancer Epidemiology and Genetics (DCEG) - worked together to ensure the integrity of the analysis, forming the Collaborative Group on Epidemiological Studies of Ovarian Cancer, under the leadership of Dr. Valerie Beral and colleagues at Oxford University's Cancer Research UK Epidemiology Unit.
The absence of proven screening methods for ovarian cancer make these findings all the more welcome. But the issue is not straightforward, because calculating "the net effect on women's health is fraught with uncertainties," wrote Drs. Eduardo L. Franco and Eliane Duarte-Franco of McGill University in Montreal in a comment accompanying the article. They went on to list possible side effects of OCs as increased risk of thromboembolism, heart disease, migraine, liver disease, and several other relatively uncommon conditions.
The analyses were not focused on comparing the benefits and risks of OCs, explains DCEG's Dr. Brinton, but only examined their effect on ovarian cancer risk. In the absence of detailed risk-benefit data, including currently unknown risks, such as cancers in women who have taken OCs and later take long-term hormone replacement therapy, she says, "This meta-analysis does not recommend widespread prescription of OCs as a preventative measure against ovarian cancer."
Dr. Beral commented that while OCs may pose a slight increased risk of breast and cervical cancer, the effect is small and disappears once the drugs are no longer being used, as contrasted with the ongoing protective effect against ovarian cancer.
Dr. Karlan added, "Ovarian cancer remains a disease with a high mortality due [mainly] to our inability to reliably diagnose it at an early stage. Women are concerned about this risk." She noted that it is important for women to be aware that OCs reduce that risk when discussing their contraceptive choices with their health care providers.
—Addison Greenwood
Sorafenib Increases Risk of High Blood Pressure
A meta-analysis published online January 24 in Lancet Oncology reports that patients receiving the standard clinical dose of sorafenib (Nexavar), an anticancer drug that targets the growth of tumor blood vessels, or angiogenesis, have a significantly increased incidence of hypertension.
Previous studies have found an increased risk of hypertension with the use of other targeted drugs and antiangiogenesis agents, including sunitinib (Sutent). To see if sorafenib also increases this risk, and subsequent risk of heart attacks and other serious cardiac events, the authors combined clinical trials data from three published papers and six meeting abstracts that included data on hypertension for patients assigned a starting dose of 400 mg of sorafenib twice daily, which is the current starting dosage approved by the FDA.
From these 9 studies, 4,599 patients were available for analysis; 3,567 received sorafenib and the other 1,032 served as controls. Data on all grades of hypertension were available from 3,363 patients enrolled in 7 trials. The overall incidence of all-grade hypertension was 23.4 percent in patients receiving sorafenib. Patients taking sorafenib were approximately six times as likely to develop any grade of hypertension as the control patients.
Data on high-grade hypertension, which often requires treatment with multiple antihypertensive drugs or discontinuation of sorafenib, were available from all 3,567 patients in the 9 trials who received the drug. The overall incidence of high-grade hypertension was 5.7 percent for these patients.
"The hypertensive and cardiovascular side-effects of sorafenib need thorough postmarketing surveillance and reporting, and future studies will be needed to identify the mechanism and appropriate treatment of sorafenib-induced hypertension," conclude the authors. In particular, they explain, further studies need to identify the classes of antihypertensive medications that can be safely given in tandem with sorafenib to minimize potential drug-drug interactions and possible interference with the efficacy of sorafenib.
Clinical Outcomes in Colon Cancer Linked to microRNA Gene
Colon tumors that produced high expression levels of a microRNA gene called miR-21 were associated with poor survival and therapeutic outcome in two patient populations, one in the U.S. and the other in China, according to a study in the January 30 Journal of the American Medical Association.
Like other microRNA genes, miR-21 produces short strands of RNA that control multiple genes, including some involved in cancer. The findings support a growing view that this gene, which shows increased activity in more than a dozen major cancers, may be a useful biological marker and therapeutic target.
"We are interested in this gene in part because our results may have implications for other cancers," said Dr. Curtis Harris of NCI's Center for Cancer Research (CCR), who led the study. "And a therapy directed against miR-21 may be effective against a variety of cancers." He cautioned that the results are preliminary and potential therapies may be years away.
The researchers first profiled microRNA gene activity in colon tumors and matched normal tissues from 84 patients from Maryland, and they validated the results in 113 patients from Hong Kong. The most striking finding was the association between high miR-21 activity in tumors and poor survival and therapeutic outcome in patients receiving adjuvant chemotherapy based on 5-fluorouracil. The associations were consistent even though slightly different techniques were used to assess microRNA activity in each group.
The results also indicate that microRNA gene activity is systematically altered in colon tumors compared to normal tissues. "There are systematic changes in microRNA expression during the cancer process," said first author Dr. Aaron Schetter of NCI's CCR.
Protein in Breast Tumors Does Not Predict Chemotherapy Benefit
High levels of the protein Ki-67 in breast tumors did not predict which women in two clinical trials would benefit from chemotherapy added to endocrine (antiestrogen) therapy. Some studies have suggested that the protein, which is associated with cell proliferation, might be used to identify women with early-stage disease who may benefit from adjuvant chemotherapy after surgery and endocrine therapy.
To test this idea, Dr. Giuseppe Viale of the University of Milan and his colleagues in the International Breast Cancer Study Group retrospectively assessed Ki-67 expression in tumors from patients involved in two randomized trials - each of which compared endocrine therapy given after chemotherapy with endocrine therapy alone. The analysis included only women with early-stage, lymph node-negative disease.
Although high levels of Ki-67 expression did not predict a chemotherapy benefit, they were prognostic of poor survival. "Other biomarkers will be required to define which patients with endocrine-responsive, node-negative early breast cancer would benefit from the addition of adjuvant chemotherapy to endocrine therapy," the researchers conclude in the February 6 Journal of the National Cancer Institute (JNCI).
The study supports the long-held position of the American Society of Clinical Oncology Tumor Marker Expert Panel that measurements of the cell cycle, such as Ki-67 expression, should not be used to make decisions about chemotherapy.
In an accompanying editorial, Dr. Matthew Ellis of Washington University in St. Louis says that biomarker studies with negative results that can exclude a positive interaction are important to publish because "clinging to a long-favored but incorrect hypothesis in the face of negative evidence impedes scientific and clinical progress."
Survey Highlights Threat of Global Tobacco-Related Mortality
Results of a new World Health Organization (WHO)-led survey of youths ages 13 to 15 suggest that the already alarmingly high number of tobacco-related deaths estimated to occur annually by 2020 may be too low, officials from the Centers for Disease Control and Prevention (CDC) and colleagues report.
By 2020, global tobacco-related deaths are estimated to double from 5 million a year to 10 million. Approximately 70 percent of these deaths will occur in developing countries.
But the results of the most recent Global Youth Tobacco Survey (GYTS) - an international, school-based survey conducted in 140 WHO member nations and other sites - suggest the situation may be worse than previously thought, wrote Dr. Charles W. Warren and colleagues in the January 25 Morbidity and Mortality Weekly Report.
Among the findings are a higher prevalence of young female smokers compared with adult females, the "high susceptibility" to smoking in the next year reported by never-smokers, and elevated levels of exposure to secondhand smoke.
Other key findings included the similar prevalence of cigarette and other tobacco product use and the high percentage of respondents who had recently bought tobacco products at a store without being refused service. Seventy percent of respondents who smoke expressed an interest in quitting, while 80 percent of all respondents supported a public ban on smoking.
"The findings in this report suggest that interventions that decrease tobacco use among youth (e.g., increasing excise taxes, media campaigns, school programs in conjunction with community interventions, and community interventions that decrease minors' access to tobacco) must be broad-based, focused on boys and girls, and have components directed toward prevention and cessation," the authors wrote.
Expanding the Search for Cancer Drug Targets
Two studies in the February 1 Science describe a genome-wide strategy for discovering "essential" genes in cancer cells that are toxic to the cells when silenced. These genes may lack the hallmarks of cancer genes, such as mutations or increased activity; however, they are essential for cell survival and proliferation, making them potential drug targets.
The strategy, described in the first study, exploits a natural defense mechanism in cells that blocks invading viruses by degrading viral RNA. Researchers now use this mechanism, known as RNA interference, as a way to target and silence genes within the cell. But technical constraints have prevented researchers from doing this type of screen on a genome-wide scale.
During the last 6 years, Drs. Stephen J. Elledge of Harvard Medical School, Gregory Hannon of Cold Spring Harbor Laboratory, and their colleagues have been working to change that. Among other advances, the researchers developed libraries of short hairpin RNA molecules that can silence every gene in the human and mouse genomes. They also created a system for using molecular tags, or bar codes, to determine which genes were toxic to cancer cells when deleted from the cells.
As reported in the second study in Science, the researchers screened several thousand genes in colon and breast tumor cells, as well as in normal cells - using some 10,000 short hairpin RNAs. They identified a few dozen genes that, when silenced, impaired the growth of cancer cells but not normal cells. The researchers believe the results are preliminary but promising.
The strategy could complement The Cancer Genome Atlas and other large-scale efforts to catalog genetic differences between tumor cells and normal cells, they continued. Specifically, the screens could reveal potential therapeutic targets that might otherwise be missed.
"I've always felt that the focus on oncogene addiction in developing cancer drugs was missing a lot of other cancer drug targets," says Dr. Elledge, referring to the phenomenon where tumors become dependent on certain cancer-causing genes. "Cancer cells seem to depend on a lot of genes that are not oncogenes, but they are important nonetheless. We call this non-oncogene addiction."
His team is preparing to apply the strategy against the entire human genome. At the same time, they hope other researchers will begin to apply the tools and the methods to many different types of cancers. Now that the resources have been developed, carrying out the experiments is relatively cost effective, the researchers note.
Study Finds No Link Between Hormones, Prostate Cancer
An analysis of the original data from 18 prospective studies indicates that prostate cancer risk is not influenced by levels of certain circulating sex hormones in the blood, reports an international research team.
Published early online January 29 in JNCI, the analysis pooled data from studies that included 3,886 men with prostate cancer and 6,438 controls. Contrary to what has long been suspected but never definitively established, no association was found between prostate cancer risk - regardless of stage or grade - and levels of various androgens as well as estradiol, a form of estrogen.
Further, reported Dr. Andrew Roddam of the University of Oxford and colleagues from the Endogenous Hormones and Prostate Cancer Collaborative Group, "there was no evidence of interactions between concentrations of any of the hormones considered and risk of prostate cancer." There was, however, a slight reduction in the risk of low-grade, localized cancer associated with circulating levels of sex hormone-binding globulins (SHBGs).
"The factors that promote localized or nonaggressive prostate cancer may be entirely different than those that promote fast-growing, high-grade prostate cancers," wrote Dr. Paul Godley and colleagues from the University of North Carolina at Chapel Hill, in an accompanying editorial. "Because most of the cancers included in these studies were localized and low-grade, pooling data from many studies allowed a sample size that was large enough to perform subanalyses of advanced and high-grade cancers, and the power to investigate interactions among hormones and [SHBGs]."
The study results suggest that "perhaps it is time for research efforts to focus instead on developing more sophisticated hypotheses and novel study designs," the editorial concluded, which can be facilitated by NIH and NCI programs already in place, including the NIH Roadmap and biospecimen storage systems.
Budget Proposal Highlights Cancer Research Progress, Priorities
Among the most valuable communication tools created as a result of the National Cancer Act of 1971 is the NCI's annual report on The Nation's Investment in Cancer Research, which was released this week. Often referred to as the "bypass budget," this report is intended to directly inform the President and guide the administration's budget request to Congress for NCI funding.
It was designed by its originators, led by Rep. Paul Rogers, to lay out in detail for the President what is needed to make as rapid progress as possible to change the course of this disease, and to provide NCI with the resources required to lead the National Cancer Program.
The Nation's Investment tells the story of scientific opportunity, emphasizing critical areas of progress in cancer research and highlighting key NCI programs that will drive future gains. It also offers insight into NCI's scientific planning and priorities, including what is called the "professional judgment budget."
This budget contains two different proposals: the budget NCI leadership believes is needed to simply sustain the National Cancer Program in its current state, and the budget required to launch new and expand current initiatives that NCI feels can hasten progress.
For fiscal year (FY) 2009, NCI's proposed budget to simply sustain our current level of activities is approximately $5.2 billion, while the proposal to accelerate progress is approximately $6 billion. By comparison, NCI's FY 2007 budget was approximately $4.8 billion.
Any report of this kind being delivered in 2008 cannot escape some difficult facts, namely that we have been operating under a flat budget for the last 4 years. And because of the continued brisk pace of biomedical inflation, the chief result has been a 12 percent reduction in NCI's purchasing power over that same period.
This lost purchasing power has had serious consequences. They include extramural laboratories cutting back on postdoctoral fellows, fewer resources with which to conduct needed clinical trials and fewer patients in already funded trials, and scaling back important programs and foregoing the launch of new programs, to cite just a few examples. And one particularly concerning repercussion of such problems is the serious impact on promising young investigators, many of whom have been choosing alternate career paths.
While progress will continue in all important areas of cancer research, it is clear that the pace of our progress is closely aligned with our available resources and, therefore, will be significantly slowed.
The Nation's Investment in Cancer Research illustrates how NCI is using its resources to support the best science and ensure continued advances, with an acute focus on how we are establishing the necessary infrastructure and programs to more closely connect important components of the cancer and larger biomedical research communities.
These areas include critical initiatives like the Glioma Molecular Diagnostics Initiative, a collaborative effort spearheaded by NCI's Dr. Howard Fine. The GMDI is bringing together NCI cancer centers and cooperative groups, the pharmaceutical industry, brain tumor consortia, and other NIH institutes to develop more individualized therapies for gliomas, particularly glioblastomas, a highly aggressive and often fatal type of brain cancer.
We are creating new connections through the National Community Cancer Centers Program, which will bring clinical trials closer to patients in their communities and allow us to conduct important research on quality of and disparities in care.
We are recruiting researchers from different disciplines to jointly tackle the most urgent problems in collaborative research networks. For example, the Tumor Microenvironment Network is enlisting cancer biologists, pathologists, and bioinformatics specialists, among others, to delve further into what we now understand is the critical role a tumor's immediate environment plays in its development and metastatic potential.
Through the Chemoprevention Research Consortium, we are translating promising lab results of new chemoprevention agents into phase I and II human clinical trials, setting the stage for the phase III trials that can determine the most effective and safest chemoprevention drugs for patients at increased cancer risk.
We are connecting the past and future through NCI's rapidly evolving training programs to help produce the next generation of cancer researchers, and via NCI's Spanish-language Web site, we are reaching out to native Spanish speakers with vital information on cancer and cancer research.
Information on all of this and much more is in this year's report, and I encourage the cancer community to take advantage of it and other NCI communications tools, both for your own information and to inform your own research or outreach efforts.
Dr. John E. Niederhuber
NCAB Hears Update on NCI Budget
Another highlight during the morning session was a presentation by NIH Director Dr. Elias Zerhouni. He shared data on the aging of NIH-funded investigators. This accelerating trend threatens to "de-prime the pump" in the coming years for developing new investigators who are able to get first-time grants and renewal grants, said Dr. Zerhouni.
The NCAB meeting will conclude tomorrow afternoon. A full copy of the meeting agenda can be found at http://deainfo.nci.nih.gov/advisory/ncab/145_0208/agenda.pdf. A videocast of the 2-day meeting can be found later this week at http://videocast.nih.gov/PastEvents.asp.
EDRN Report Released
Women with Breast Cancer Talk about Pain
"Make sure people are aware of what I found out, that you don't have to be in pain." - Breast cancer survivor, Toronto
Pain remains a major problem for people with cancer. Despite recent advances in understanding and managing pain, the majority of cancer patients experience pain that goes untreated or undertreated. A number of factors may help explain this, with the health care system, clinicians, and patients all playing a role.
Busy physicians and nurses may lack incentives to spend time talking with patients about managing pain, for instance, while government regulations limit the use of certain pain medications. Many health care professionals themselves are not adequately trained in managing pain effectively.
Many patients, for their part, are reluctant to mention pain. Some may not want to distract physicians from treating the cancer, or they may view talking about pain as complaining - as not being a "good" patient.
Most important, many assume that pain and cancer go hand-in-hand - that pain is inevitable, something to "tough out." In fact, cancer pain can be effectively controlled in most cases, and experts have been fighting these misconceptions for years.
Such beliefs were common among 18 Canadian women with breast cancer who were recently interviewed about their experiences with pain. A summary of the interviews, published in the February Journal of Pain and Symptom Management, provides a comprehensive look at questions about pain from a group of cancer patients.
The interviews also offer a window on experiences that were, in some cases, made more difficult because the women did not know how to get help for their pain. Unfortunately, this is not uncommon among cancer patients, says Jackie Bender, a doctoral student at the University of Toronto and the study's first author.
Her interviews consistently showed that patients lacked knowledge about the options for controlling pain, the services available for managing pain, and how to access them. She was struck that patients did not initially know such services existed.
As one woman said, "Why should I know that there are pain doctors or pain specialists out there? I had no idea."
"Many of the women I spoke to experienced severe pain that had not been managed well," says Ms. Bender. "Fortunately, when I spoke to them, they were receiving help from pain specialists." At the time of the interviews the majority - more than 70 percent - were experiencing mild pain.
One woman commented, "I wish I knew then that there was a painkiller like this to alleviate my pain because... then, I wouldn't have suffered so much, right?"
The descriptions of pain were sometimes accompanied by concerns about addiction and tolerance, particularly with respect to opioid drugs. Such concerns are common among cancer patients, though experts stress that few people who take pain medications for cancer become addicted to the medications.
Many women in the study avoided or discontinued pain medication out of fear of side effects. At the same time, some participants wanted to learn about alternative and nontraditional approaches to pain management.
The women also wanted to learn about the pain experiences of others. "People were seeking out others for support, as well as for validation that their own pain was typical or normal," says Ms. Bender.
The participants' questions - in all, more than 200 - may be relevant to other cancers and other diseases. The researchers, led by Dr. Alejandro R. Jadad of the Centre for Global eHealth Innovation at the University of Toronto and the University Health Network, are now looking at pain from the perspectives of patients with other chronic conditions, or who belong to different ethnic or cultural communities.
So far, the research has identified some core themes across the patient populations as well as themes that are specific to each group.
As a next step, the researchers are developing an interactive Internet tool that patients can use to explore questions about pain and communicate with other patients in pain before meeting with physicians and nurses.
"We see it as a clinical appointment preparation tool for people who have pain," says Ms. Bender, noting that patients and health professionals have to communicate effectively about pain. The Web site aims to help patients organize their questions so that they can be addressed during appointments.
"If pain is to be managed adequately, efficient mechanisms are needed to help patients identify and articulate their questions and get answers," the researchers wrote.
The Web site could certainly help, but real progress will involve all parties. Patients have to articulate their needs, while clinicians must create environments where people feel comfortable talking about their fears and concerns about pain.
"It is important to address pain from the very beginning of cancer treatment because unrelieved pain can further erode an already compromised quality of life," says Ms. Bender.
As more and more people survive cancer and return to productive lives, managing pain will be critical to ensuring a good quality of life for each one.
As one woman said, "I don't want pain to stop my life. I want to be able to live with it."
—By Edward R. Winstead
Combination Therapy for Invasive Bladder Cancer
Name of the Trial
Principal Investigators
Why This Trial Is Important
Previous clinical trials of this method have included only patients who were eligible for cystectomy, in the event that the bladder-preserving therapy failed. For patients who are not suitable for cystectomy, no standard treatment options currently exist.
In this trial, patients with invasive bladder cancer who are not suitable for cystectomy will be treated with the drug paclitaxel and daily radiation therapy. Also, patients whose tumors test positive for the protein HER2 will be treated with the monoclonal antibody trastuzumab (Herceptin).
Some studies have suggested that 40–80 percent of bladder cancer tumors produce increased amounts of HER2 and that patients with such tumors tend to fare poorly compared to patients whose tumors do not overexpress this protein. Trastuzumab binds to HER2 on the surface of tumor cells and initiates a cytotoxic process.
"Patients with muscle-invasive bladder cancer who are not suitable for surgery have few options for treatment," said Dr. Michaelson. "With this trial we're testing what we hope to be a fairly gentle means of treatment using combination therapy developed for bladder preservation."In addition to trying to establish a safe and well-tolerated regimen that can be tested in larger clinical trials, we hope to clarify the role of HER2 in bladder cancer and determine if trastuzumab can help improve outcomes for patients whose tumors overexpress that protein," Dr. Michaelson added.
For More Information
An archive of "Featured Clinical Trial" columns is available at http://www.cancer.gov/clinicaltrials/ft-all-featured-trials.
NIH to Begin Enforcing Public-Access Policy in April
Peer-reviewed journal articles based on NIH-funded research will soon become available to the public at no cost through the PubMed Central online database, which is administered by the NIH National Library of Medicine (NLM). This policy goes into effect on April 7 and will affect all intramural and extramural research funded in fiscal year 2008 and beyond.
"Public access is a public good," says Dr. Norka Ruiz Bravo, NIH deputy director of extramural research and director of the NIH Office of Extramural Research. "The mandatory policy makes publications resulting from NIH-funded research accessible to all - the public, health care providers, educators, and scientists, among others. Public access will help advance science and improve human health."
The policy is outlined at http://publicaccess.nih.gov and is legislated by the Consolidated Appropriations Act of 2008, which followed years of lobbying by proponents of public access and several intermediate Congressional bills.
It is estimated that approximately 80,000 journal articles each year are published as a result of NIH-sponsored research. Previously, study authors were asked to voluntarily submit their published manuscripts, but far fewer of them did than was hoped.
To enforce the new policy, NIH has instituted a condition in all grants and cooperative agreements such that, in accepting funds, researchers agree to submit their manuscripts to PubMed Central upon acceptance of publication. Articles can be embargoed for up to 12 months. After the embargo, however, the article will be made publicly available in PubMed Central.
More than 300 journals have an agreement with NLM where they automatically submit articles to PubMed Central, and the authors who want to publish in these journals need not do anything more. But if an author wishes to publish in another journal, they must submit the article themselves on the Manuscript Submission System (www.nihms.nih.gov). Beginning on May 25, authors must include a PubMed Central reference number for each article that they cite in their grant applications and proposals.
Retroactive submission of articles that were published before the April 7 deadline is not mandatory, but authors are encouraged to submit these manuscripts if they have appropriate copyright permission.
To assist intramural and extramural researchers with adherence to the new policy, the NIH Office of Extramural Research is planning a series of workshops in 2008. The office will announce these workshops on its Web site at http://grants.nih.gov/grants/oer.htm.


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16 U.S. Code § 2005b - Repealed.
Section, Pub. L. 104–127, title III, § 386,Apr. 4, 1996, 110 Stat. 1017, related to conservation of private grazing land. See section 3839bb of this title.
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Check out this free chore chart printable! It's colorful and such an easy way to keep track of who has done their chores. Whether you reward with a sticker or money, it's just a easy way for the whole family to see what has been accomplished.
I'm attaching mine to a clipboard, one for each child and hanging them on the wall. Pretty cute!
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DIY: How to Make New Year's Eve Noisemakers
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Tote bags never fall out of favor, and there's a good reason why: The humble tote can hold just about anything. The beauty of the tote is its hands-free nature – sling it over your shoulder and you're ready to go. SPENCER DEVINE's Brooklyn-made bags can transform from totes to backpacks in a few quick slips of the straps. An oversized canvas and leather tote by Roque Bags can serve as a beach bag or a companion for a weekend away – after all, Roque himself was an intrepid traveler. Perhaps simplicity suits you best? Misoui's handcrafted leather shopper is just your style. Or go for a handmade option by Téo+NG, and take a peek inside their Parisian studio here.


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Hannah's Q & A
Who's your favorite sports team, and why?
Dallas Mavericks. It was that or be a Cowboys fan. I can't stand Romo. Or Jerry Jones for that matter.
What's your favorite movie quote?
"YOU BOYS LIKE MEX-EE-CO?!" -Super Troopers
What's your favorite video game, and could you kick our butts at it?
Super Smash Brothers for N64. And yes, so long as I'm playing as Pikachu and he's wearing the green party hat.
Piercings/Tattoos (How many? Where?)
None, currently! I had a tongue ring back in my college days though!
What's the most embarrassing song on your iPod?
Hahahaha "The Warrior" by Patty Smyth and Scandal. I know all the words too... Don't judge.
What's your best party trick?
A lot of parties typically result in me doing caricatures and cartoons of people.
What's the most memorable pick-up line you've ever heard?
"Got any raisins? No? Well, how bout a date?" It totally worked!
What's the worst job you've ever had?
Sunday School Teacher.
What's the most dangerous thing you've ever done?
Divide by zero.
It's 4AM after a crazy night out – what are we eating?
I'll make us a venison Frito pie! Yum :)
What's the strangest thing in your fridge right now?
There is nothing strange in my fridge. I'm a woman. Kitchens are my monopoly.
What's the naughtiest thing you've ever done in public?
I've been known to take neighbors' Christmas decorations (reindeer, blow-up Santas/ snowmen, etc.) and put them in compromising positions with each other. It's my only actual Christmas tradition, but I've yet to skip a year since I was 12!
What do you feel sexiest wearing?
I pretty much feel sexy in anything or nothing. It's my cross to bear...
Tell us a joke.
What does a walrus and Tupperware have in common? They're both looking for a tight seal :)


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Cross D Bar Trout Ranch - The place to RELAX!Westcliffe, Colorado Fishing TripsFamous, old, high mountain cattle ranch located in SC Colorado. Easy to find and ADA compliant. Awesome trout fishing and a variety of accommodations including a RV Park. Spectacular scenery, family friendly, pets and groups welcome. ... $21 Per Night
Colorado Hunting and Fishing Horse Pack in TripDenver, Colorado Fishing TripsLodge or pack in fishing or hunting elk, deer, moose, bear, hogs, exotics or turkey archery, muzzleloader, rifle. Multiple locations in Colorado and 35 other states plus Canada....
Quality Inn Centennial.Colorado, Colorado Hotels & ResortsWelcome to the Quality Inn DTC located off I-25 and Geddes Avenue in the heart of the Denver Tech Center Area. All guestrooms include free high speed internet ... $65 Per Night
Hilton Garden Inn Denver/highlands Ranch.Colorado, Colorado Hotels & ResortsThe hotel is situated close to all the attractions of Denver and the surrounding areas full of world class shopping, dining and golf. ... $79 Per Night
Homestead Dtc-greenwood.Colorado, Colorado Hotels & ResortsThis all-suite hotel offers rooms with kitchens approximately 12 miles from downtown Denver and 30 miles from the Denver airport. Guests will find a fitness ... $41 Per Night
Guided Private Backcountry AdventuresAspen, Colorado Rock ClimbingAspen Alpine Guides provides guided private hikes, rock climbing, mountaineering, backcountry hut trips, and winter snowshoe and ski trips into the pristine backcountry around Aspen and the Roaring Fork Valley.... $295 Per Group
Luxury Custom Motorcycle and Sports Car ToursVail, Colorado Motorcycle ToursLuxury motorcycle & sports car tours in Colorado, Wyoming, Montana, Idaho, South Dakota, Utah, Canada, British Columbia, Alberta, Alaska, Italy, and Spain. We design the perfect tour for you with or without a guide. All inclusive tours available....Starting at $500 Per Night
Colorado and the West Motorcycle ToursArvada, Colorado Motorcycle ToursWe offer guided Motorcycle Tours that are a single day to multi day tours. We also specialize in private group tours....
Private Health Getaway in Boulder, ColoradoBoulder, Colorado Fitness & Weight LossWith Fit Health into Life you'll enjoy private daily guided hikes and private nutrition counseling, and you'll learn to fit exercise and healthy eating into your life, so it's not a burden, it becomes routine, and you actually enjoy it....Starting at $1,200 Per Person
Trains Across Colorado.Colorado, Colorado Sight-Seeing ToursIt is easy to see why Trains Across Colorado was our most popular escorted tour of 2005. Wtih the Pikes Peak Cog Railway taking you to the clouds and the Durango & Silverton Narrow Gauge Railroad one of the most exciting train journeys in the world.... $1,354 Per Person
San Juan Mountain GuidesRidgway, Colorado Sight-Seeing ToursSJMG offers personalized, professional instruction and guiding in Ice climbing, Rock climbing, Backcountry Skiing and Avalanche Training, Alpine Mountaineering, and International Expeditions. Our home base is the picturesque town of Ouray, Colo... $135 Per Person
A Grand Adventure Balloon TourSummit County, Colorado Scenic Flight ToursHot air balloon the mountains closest mtn flight to Denver and Summit. Views are breathtaking, near RMNP. ...


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Denison does provide off campus interviews. By providing the information on this form, it will help us to serve you more accurately.
Popular Items
Submit the Common Application along with the Denison Supplement (Part III). The Supplement can be found on the Common Application website once you have added Denison to your list of schools. If you complete the Common Application online, we will waive the $40 application fee. If you prefer to send in a hard copy, you will need to visit Common Application Forms to print off the application. Please include a $40 application fee with the hard copy and mail it to: Denison University, Admissions Office, P.O. Box 740, Granville, Ohio 43023.
This information has been disclosed to you from records whose confidentiality is protected by Federal Law. A general Authorization for the release of medical or other information is not sufficient for this purpose.
Any Licking County resident over 30 years of age may become a Denison University Community Scholar. A Community Scholar may enroll in only one non-credit course per semester. There is no limit to the number of semesters for which a scholar may enroll. Registration is on a space-available basis.
This form is for use by Denison students, faculty and staff. All unauthorized requests will be deleted.
The Office of Web, Mobile & Social Strategy and Development handles publishing & organizing content for the Denison.edu public website. Use this form if you need to add or update pages, information or forms/PDFs for use by a public audience.
Early Decision is the application process in which students make a commitment to a first-choice institution, where, if admitted, they definitely will enroll.
If you would like to apply for need-based financial aid, please submit this Early Decision Financial Aid Application. If you have questions about the need-based financial aid process, fell free to contact the Denison Financial Aid Office at 1-800-DENISON.
Denison University employees and spouses/same-sex domestic partners, who are non-degree seeking students (not admitted through Admissions) are eligible to participate in this program and take course work for credit or audit. For further detail on staff educational benefits and eligibility please refer to the Benefits section in the Staff Handbook
Employers can connect with students at Denison University by utilizing the On-Campus Recruiting (OCR) Program, which runs during the months of September, October, November, February, March and April. If you would like to schedule on-campus interviews, information tables or information sessions, please complete the online on-campus recruiting form.
Organizational Studies Application for Enrollment and Recommendation form for entry into the program.
If you would like to initiate a voluntary withdrawal from Denison, you must complete an Exit Form and then contact to schedule an exit interview.
Your Free Application for Federal Student Aid (FAFSA) can be selected for review in a process called verification. The law says that before awarding Federal Student Aid, we may ask you to confirm the information you and your parents reported on your FAFSA if you are a dependent student.
Your Free Application for Federal Student Aid (FAFSA) may be selected for review in a process called verification. The law says that before awarding Federal Student Aid, we may ask you to confirm the information you reported on your FAFSA.
We are delighted that your son or daughter will soon be joining us as a member of the Denison community. We want to make sure you receive all parent mailings, so please fill out our Family Information Form available at the link below through online submission. Please include grandparents' names and addresses if they would like to receive campus news as well.
If you have questions about the need-based financial aid process, fell free to contact the Denison Financial Aid Office at 1-800-DENISON or email@example.com.
Denison University sponsors a non-residential Host Family Program that brings together international students with local families. Host families help new international students adjust to their new cultural surroundings. They also provide entrée into the local community and off campus life. In turn, local families are able to expand their own horizons through friendship with a student from another country. Many relationships between host families and international students last long after the student has graduated from Denison.
Denison University sponsors a non-residential Host Family Program that brings together international students with local families. Host families help new international students adjust to their new cultural surroundings. They also provide entrée into the local community and off campus life. In turn, local families are able to expand their own horizons through friendship with a student from another country. Many relationships between host families and international students last long after the student has graduated from Denison.
Request a book or article from another school if Denison, CONSORT, & OhioLINK don't have what you're looking for.
The purpose of the Certification of Finances is to help colleges and universities obtain complete and accurate information about the funds available to international applicants
The International Student Financial Aid Application is designed to gather information from international students who are applying for financial aid at colleges and universities in the United States.
A Licking County Scholar is defined as one currently completing his/her senior year at a Licking county High School, having earned a high school GPA of 3.4 or above, and is simultaneously registered for one college level course at Denison University. No application fee is required. If after any semester a Licking County Scholar's semester average is less than 2.00, his or her eligibility for participation in this program shall be terminated.
Students who have previously acknowledged their preference for their federal student loans can request changes to the loan(s) that were offered by completing the Loan Update form and returning to the Office of Financial Aid.
Track One focuses on the workings of American national government and offers a congressional internship as well as coursework.
Track Two focuses on United States foreign policy and international affairs and offers coursework in foreign policy, comparative politics and international politics, as well as internships with the Washington Semester Program.
The Make It Happen! workshop will consist of classroom presentations, discussions, and field trips. Participants are encouraged to identify an area of interest that they can use as a focus for their work during the workshop and beyond.
The May Term internship is an educational experience for students interested in teaching or other educational endeavors. During the internship the student acts as an apprentice to the site supervisor; in schools this takes the form of working a regular teacher's schedule for approximately three weeks. If the classroom teacher accepts the responsibility of directing an intern, then it is reasonable to expect the intern to complete certain objectives.
Are you interested in further information about Music at Denison? Please fill out the Prospective Student Form and a representative from the Music Department will contact you to assist with any questions you may have.
Complete and return this form if you are interested in participating in one or more of the musical ensembles at Denison or are interested in taking private lessons with a member of the music faculty. Even if you do not choose to complete this form, you can still sign up for lessons and ensembles through the second week of the semester. However, this form helps by giving us an early idea of which and how many students are planning to participate in music at Denison and what their abilities and interests are at the start.
All application materials for the Oak Ridge Science Semester (ORSS) must be received by Denison University by March 1. It is extremely important to submit all application materials by this deadline. Typically, you will be notified about acceptance into the program within 3-6 weeks after the application deadline.
Optional Practical Training (OPT) provides an opportunity for F-1 visa holders to gain up to one year of experience in their field of study during their annual summer vacation, while school is in session (if training does not exceed 20 hours per week), and/or after graduation. Most students choose to save OPT until after graduation. A job offer is not required to apply for OPT. Students may apply before graduation or within the sixty (60) day grace period following graduation.
The Denison Cycling Orientation offers an opportunity for 10 members of the incoming class to take a four-day back-roads excursion through the beautiful natural areas of central Ohio.
Denison Experience in Urban Culture and Expression (DEUCE) enables 24 entering First-Year Students, along with two faculty members and three Student Staffers to explore the vibrant urban arts culture that only a big city can generate. After a day of getting to know one another, the group will travel to Philadelphia where they will meet with visual and performance artists to talk about the role the arts play in social change.
Denison Outdoor Orientation offers an opportunity for 48 members of the incoming class and 12 faculty/staff and student leaders to backpack for three days in the National Forest in Kentucky. After a day on campus preparing for the trip, participants will journey to the National Forest, where they will spend three days hiking, camping and relaxing. The purpose of this program is to provide students a unique, challenging, and enjoyable transition to life at Denison by forming bonds and friendships with other entering first-years – all while on the trail.
The Denison Service Orientation (DSO) is an intense direct-service experience designed to help incoming students adjust to college, build strong friendships, and realize the possibilities available to them at Denison. Approximately 24 students from the incoming class will travel to Washington D.C. for a service experience related to homelessness, hunger and HIV/AIDS issues. During the program participants will engage in leadership training, group building, issues education and direct service.
June Orientation is an optional but highly recommended orientation program for students who are new to the college experience. June-O focuses on the academic preparation and course pre-registration of the entering class.
If you plan to use Denison's shuttle service, we ask that you provide your travel information to us once it is known, including arrival and departure dates, times, and flight numbers.
Paving the Way encourages all entering students to participate in this program, although its primary focus is to assist traditionally under-represented student populations in transitioning to the academic, cultural, and social climate at Denison University.
We invite you to begin your college experience by participating in the Pre-Orientation for Students Coming from Abroad. This program is especially valuable for students who will transition to a new culture and/or country as they begin their college career at Denison, whether that student is a foreign national or a U.S. citizen who has lived outside of the U.S.
Denison Sustainable Farming Orientation offers an opportunity to work on projects such as harvesting, preserving (canning, drying, freezing), repairing and building trails, and managing farm animals, and forming bonds and friendships. It allows for up to 18 members of the incoming class and 3 to 5 faculty/staff leaders to practice sustainable farming by living and working on the The Flying J Farm, a sustainable farm located 20 minutes from Denison.
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The South Side Community Organization will install new officers at its annual dinner meeting Feb. 9.
The Saturday program will begin at 6 p.m. with a ho-host bar, followed by dinner, installation of officers and entertainment by Nuestra Herencia Mexicana Ballet Folklorico.
Tickets, $20 per person, can be reserved by calling Frank Garcia, 832-7152, or Lynda Mendoza, 603-4054.
The organization, which sponsors community programs primarily on the city's Southside, is also accepting new members for 2013.
Regular meetings are the first Wednesday of each month at Guadalupe Community Center, 126 W. First St.
Annual dues are $30 for an individual and $50 for a family of two adults and any children younger than 18.
For information: Anita McManus, 814-6580; Christina Hashimoto, 740-5208; or Susie Lopez, 836-3643.
TLAC selling tickets for crab feed
The Tracy Latin Athletic Club will host its annual crab feed Saturday, Jan. 19, at the Masonic Temple, 1601 N. Tracy Blvd.
The evening, which raises funds for the TLAC scholarship program, will begin at 6 p.m. with a no-host bar, followed at 7 p.m. with a crab dinner featuring fresh Dungeness crab, pasta, salad and French bread. Mike Bacchetti and crew are preparing the meal.
Door prizes and a 50/50 raffle will be featured. Music will be provided by the Alma Tropical Latin Rhythm Band.
Some tickets are still available.
For information: Matt Palomino, 640-6014.
Legion auxiliary to meet
The next meeting of the American Legion Auxiliary, James McDermott Unit 172, will begin at noon Tuesday, Jan. 22, at Perko's Café, 1321 W. 11th St.
For information: Ruth Briggs, 835-1429.
• Members of clubs in Tracy or Mountain House are invited to share news about their groups. Send email to email@example.com, call 835-3030 or leave
a note at the Tracy Press offices, 145 W. 10th St.


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Impact Foam
A thick, seamless wrap of padding provides top to bottom protection for your laptop.
Checkpoint Friendly
Designed in compliance with TSA guidelines so your laptop can stay inside the case when passing through airport security.
(based on 14 reviews)
Ratings Distribution
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of respondents would recommend this to a friend.
Reviewed by 14 customers
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Great, but I need it in a 10.1" size
By Guy
from Duluth, MN
Best Uses
It's exactly what I want, except it's not available in the 10.1" size for a Galaxy Note 10.1. What's up with that?
Bottom Line Yes, I would recommend this to a friend
Was this review helpful? Yes / No
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(5 of 10 customers found this review helpful)
The only one I could find ...
By RICHARD
from Merrimack, NH
The only one I could find that the IPod fit perfectly in.
(10 of 16 customers found this review helpful)
This sleeve is perfectly ...
By RON
from Phoenix, AZ
This sleeve is perfectly simple - I just wanted a way to protect my iPad while I carry it around and I'm not using it. This lets me do that and it still fits with my Smart Cover on. The only thing I would add is a pocket on the inside because I like to slide miscellaneous documents and things like that inside the sleeve as well.
The Case Logic for the ...
By JOHN
from Beaumont, TX
The Case Logic for the iPad is ruggedly constructed and really protects it from the environment environment. I use anytime I leave home with it. J Ayres
(2 of 2 customers found this review helpful)
I bought it becase I ...
By LISA BETH
from Stewart, FL
I bought it becase I liked the design which included the look and the colors. I am very picky and it is just perfect. I bought it for my new Ipad and it fits like a glove even with a smart cover and a bottom cover. Good job! I am happy. I also bought two more for friends. LisaBeth
(6 of 11 customers found this review helpful)
nice looking product, ...
By STEVEN
from Sacramento, CA
nice looking product, good padding for my IPad, the right price, and just what I was looking for.
protects my iPad. appears ...
By KEVIN
from Chicago, IL
protects my iPad. appears durable. good value.
(0 of 4 customers found this review helpful)
Excellent.. Perfect fit.. ...
By HARRY
from Pueblo West, CO
Excellent.. Perfect fit.. Appears very durable.
Good, quality at a ...
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from Lakeville, OH
Good, quality at a reasonable price.
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I have three pieces of ...
By BARBARA
from CHILLICOTHE, IL
I have three pieces of Caselogic and am very pleased. The case for the Ipad is fine, just wish it had a small inside pocket, but the price was right.
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Smart LEDs are an overdue addition to the WeMo family of gadgets -- thankfully, Belkin did a nice job of getting them right.
The beauty of this affordable slow cooker is its simplicity. It sticks to the basics but also boasts extras that set it apart from the competition.
Asus' new smartwatch is powered by Android Wear, and looks to classic stainless steel for an edge in the wearable war.
Pricing not available
While the Wink Hub has some design and usability kinks to work out, its affordability and versatility make it a very desirable option for whole-home automation.
Billed as a super-personal yet networked weather station, the BloomSky promises to see as well as measure the elements.
The Lumen Mini is a bluetooth-enabled mood light that's coming to Kickstarter later this month.
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Samsung's new premium line of tablets ditches app icons for widgets and includes topnotch specs and features
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Grand Theft Auto V is an absolute triumph that fires on all cylinders. It's a relevant, witty, and satirical experience that's as smart as it is completely addicting.
LG's smart fridge offers robust software you might actually use.
As long as you don't mind not being able to print from a USB flash key, the Dell B1165nfw's healthy array of extra features and quick outbound print cycle make it worthwhile for small offices with wireless access.


text: |The Nike Air Alvord 10 running shoe is for the trail runner seeking a modern, protective and durable ride with great comfort. Supportive overlays and internal midfoot strap offer a comfortable and great-fitting ride. Gusseted tongue construction helps keep debris out. Phylon� midsole and Air-Sole� unit in the heel provides excellent cushioning. High abrasion, BRS 1000� heel strike combined with multi-directional lugs give great traction and wear no matter the surface. Wt. 9.4 oz.


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Family Read-Alouds
Books for reading aloud that all ages, even preschoolers, can enjoy.
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40 listings found. Displaying 1 - 20
Simmons, Jane
Ship's Cat Doris
"When Bosun chooses a kitten to be his new ship's cat, he thinks he's a she and names him Doris! But Doris soon finds this isn't his only problem: making friends with the ship's dogs is tricky, and standing up to the shipyard bully will take a lot of courage. Will Doris ever be a true ship's cat?"--P. [4] of cover. 2010
Andrews, Jan.
Stories at the Door
Six silly stories to tickle your funnybone!
Atwater, Richard
Mr. Popper's Penguins
The unexpected delivery of a large crate containing an Antarctic penguin changes the life and fortunes of Mr. Popper, a house painter obsessed by dreams of the Polar regions.
Averill, Esther Holden
Jenny Goes to Sea
The little black cat named Jenny, along with her brothers and their owner Captain Tinker, sails around the world on a ship called the Sea Queen.
The End of the Beginning: Being the Adventures of a Small Snail (and an Even Smaller Ant)
Avon the snail and Edward, a take-charge ant, set off together on a journey to an undetermined destination in search of unspecified adventures.
Berner, Rotraut Susanne
Hound and Hare
Harley Hare and Hugo Hound are classmates, but they never talk to each other because their families can't stand one another. At a race event Harley and Hugo find themselves running neck and neck. Then a thunderstorm stops the race and results in them both becoming heroes.
Cameron, Ann
Gloria's Way
Gloria shares special times with her mother and father and with her friends Julian, Huey, and Latisha.
Cameron, Ann
Spunky Tells All
Called a troublemaker by his human family, a reflective dog defends himself and then relates the family's adoption of an aristocratic but incompetent cat, who gives him a life purpose and and new way of looking at his world.
Carris, Joan Davenport
Welcome to the Bed & Biscuit
The family animals at the Bed and Biscuit begin to feel slighted when Dr. Bender returns from a fire with something that occupies the time usually reserved for them.
Cazet, Denys
Minnie & Moo and the Seven Wonders of the World
Two cows try to save their farm by creating seven wonders and asking the other animals for donations to see them, but there is a wondrous and frightening creature in the woods that could foil the plan.
Cleary, Beverly
Ralph S. Mouse
Presents the further adventures of a motorcycle-riding mouse who goes to school and becomes the instigator of an investigation of rodents and the peacemaker for two lonely boys.
Cleary, Beverly
Ramona the Pest
Ramona works hard at being noticed in kindergarten.
Cleary, Beverly
Two Times the Fun
Jimmy and Janet, four-year-old twins, share the adventures of digging a hole to China, finding a worthy recipient for their dog biscuits, shopping for new shoes, and getting real beds to replace their cribs.
Cole, Henry
A Nest for Celeste: a Story About Art Inspiration and the Meaning of Home
Celeste, a mouse longing for a real home, becomes a source of inspiration to teenaged Joseph, assistant to the artist and naturalist John James Audubon, at a New Orleans, Louisiana, plantation in 1821.
DiCamillo, Kate
Mercy Watson to the Rescue
After Mercy the pig snuggles to sleep with the Watsons, all three awaken with the bed teetering on the edge of a big hole in the floor.
Enright, Elizabeth
Thimble Summer
Recounts the events of a nine-year-old farm girl in Wisconsin during a summer when a drought ends, her family adopts an orphan boy, a barn is built, and her pig wins a blue ribbon at the county fair.
Gannett, Ruth Stiles
Elmer and the Dragon; Illus. By Ruth Chrisman Gannett.
On their way home, Elmer and a flying dragon land on an unusual island and help some canaries uncover a buried treasure.
Giff, Patricia Reilly
Number One Kid
When Mitchell's father gets a new job and his family moves, he and his sister go to a new school where they must make new friends and adjust to new routines.
Hazen, Lynn E.
The Amazing Trail of Seymour Snail
Hoping to become a famous artist one day, Seymour Snail takes a job in a New York City art gallery, where everyone is buzzing about a "magnificent mystery artist."
Horse, Harry
The Last Polar Bears
A child receives letters from Grandfather, who has gone on an expedition with his little dog Roo, to find the last polar bears at the North Pole.
Horvath, Polly.
Mr. and Mrs. Bunny-- Detectives Extraordinaire
Middle-schooler Madeline's hippy parents have been kidnapped from Hornby Island, Canada, by foxes and Madeline, upon discovering that she can understand animal languages, hires two rabbit detectives to find them.
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Yaktrax Men's Outdoor Cabin SockItem Number: 13230494
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The Yaktrax® Outdoor Cabin sock quickly becomes your everyday style in the cold winter months with its blend of comfort, warmth and style. A full cushion design delivers unbeatable comfort while also protecting you from the unforgiving winter elements. An acrylic/wool blend works to keep your feet warm and wicks away sweat to keep you cool and dry in a YakTrax® sock that takes on whatever winter has in store.
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text:
Duke Nukem 'D-Day' Teased with ScreenshotBy Alice O'Connor and Chris Faylor, Nov 30, 2009 5:43am PST Duke Nukem's official Facebook page has been updated with a screenshot for something called "D-Day," with the action hero himself teasing that he "doesn't stay down for long."
It remains to be seen exactly what D-Day is, whether it be a a new game, the build-up to an announcement or revelation, or something else entirely. The stadium and enemy might seem familiar from the Duke Nukem Forever footage leaked in May, though those were callbacks to Duke's earlier adventures.
Series creator and Duke Nukem Forever developer 3D Realms closed its offices and laid off a majority of staff earlier this year, though the company affirms it is still working on the legally-troubled shooter. Borderlands and Brothers in Arms veteran Gearbox was working on a separate game dubbed 'Duke Begins,' though that project is said to have been postponed. And recently, rumors have surfaced of Sunstorm Interactive's 2002 side-scroller Duke Nukem: Manhattan Project coming to Xbox Live Arcade.
Meanwhile, a new trilogy of portable Duke Nukem titles is in the works at Frontline Studios. The first, Critical Mass, was expected this fall but, in true Duke tradition, seems to have slipped into 2010.
Middle-Earth: Shadow of Mordor season pass highlighted in new trailer
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Shacknews Chatty Community's Top 100 PC Games of All-Time: #10-1
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Middle-Earth: Shadow of Mordor review: simply walk into Mordor
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Super Smash Bros. Wii U game and controller bundle spotted on Amazon
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By: CurbDog x Show Full PostWould it be so bad to just want a Duke3D remake? Offer a classic 1:1 mode and maybe a more modern remix one with a few tweaks here and there. Perhaps a solid multiplayer/coop mode for good measure?
Hell who am I kidding. I'd settle for just the D3D remake with no extras. :)Dec 01, 2009 10:34pm PSTWould it be so bad to just want a Duke3D remake? Offer a classic 1:1 mode and maybe a more modern remix o... : CurbDog
By: fw_rams x Show Full Postthere's a lot of anger here. gb3dr once told me when i was bitching about some shooters years ago in their forums, that i'm maybe just tired of gaming.
So guys, maybe you are just tired of gaming too.
Maybe you need to go out a bit and do some different things and when you come back, you will see that this is a exciting time right now. We've got lots of unbelievable great games in the shelves to play. If duke makes an appearance somewhere in the near future, this would be awesome.
Yes, 3drealms might have fucked up their company by going down the wrong road too many times, but that's the business view and i know who would have bitched most about a bad duke game. YOU GUYS.
I'm the gamer and don't work / ever worked there. I loved the studio for their great games and I wish Scott and George (and everybody who secretly works for 3dr atm) all the best. I never met those two guys in person, but from the games they created and from the interviews and forum posts i've seen, they are great guys and they obviously don't deserve how some kids bitch about them. They wanted to deliver a great game, but they needed funds in a time where the crisis was hitting the industry hard. So what? Are they now the badguys?
Seriously get your own shit together. People lost their jobs there - if they are angry, ok - but hey, you maybe wasted some time on a forum where you could have spent that time playing flashminigames. Yeah, we waited about 12 years for that game. So what? it was our decision to do so. I don't miss one second of that time spent waiting for that game. I met some great people in a incredible nice fanbase.
Sorry, for this post and my fucked up english - i *might* have outed me right now as a fanboy, but if some people understand this, i've got no problem with that.
-rams/ zwiebackDec 01, 2009 4:13am PSTthere's a lot of anger here. gb3dr once told me when i was bitching about some shooters years ago in thei... : fw_rams
By: penny_flame x Show Full PostI really have no interest in Duke Nukem if Gearbox gets involved. They already fucking stole my money with that piece of shit they call Borderlands. Ugh
I really wanted Duke to come out I was really really hoping it would change gaming
Gaming is fuckedNov 30, 2009 11:04pm PSTI really have no interest in Duke Nukem if Gearbox gets involved. They already fucking stole my money wit... : penny_flame
By: squeakychimp x Show Full PostDuke Nukem is like a psycho ex girlfriend that just wont go the hell away. Sure the sex was great when you were together, but now it's just tedious and annoying. Whoever is trying to keep this series alive needs to bury this title, take their Duke Nukem 3D stories with them, and move on with their lives.Dec 01, 2009 6:22am PST
By: melt_core x Show Full PostI wish it was something else, but it's hard not to the think it's just leverage for their case against Take2...Dec 01, 2009 4:57am PST
By: Frush81 x Show Full Postis there a way to filter news by tags?Nov 30, 2009 7:53am PST
By: supamart x Show Full PostSTOP PLAYING WITH MY FEELINGS, DUKE NUKEM! YOU HURT ME TOO MUCH!Nov 30, 2009 9:55pm PST
By: PlayfulPuppy x Show Full Post3DR either need to shut the fuck up, or start releasing PROPER press packs. You know, say what they're working on, give some decent screenshots that are larger than a thimble, and stop being such secretive assholes about it.
As it stands, 3DR are the 'that guy' of the games development world. You know, that guy that says he has a pre-release copy of some popular upcoming game but for some reason whenever you ask to see it he lent it to his cousin just the other day. And his computer is in the shop. And he has to fall out of public view because the FBI headhunted him. Y'know, that guy.
They don't owe anyone anything, but if they have any semblance of respect for their fans, they really should cut the shit.
Nov 30, 2009 9:28pm PST
By: SFtheWolf x Show Full PostAm I the only one that doesn't think every scrap of news on this matter isn't part of some elaborate conspiracy 3DR has concocted for the sole purpose of raging all of you?Nov 30, 2009 8:26pm PSTAm I the only one that doesn't think every scrap of news on this matter isn't part of some elaborate cons... : SFtheWolf
By: dancingpolkabear x Show Full PostI have to admit, 3d Realms, you guys are talented, every screenshot and video is expertly done and looks very cinematic and epic, I give major props to you guys for that.Nov 30, 2009 5:36pm PSTI have to admit, 3d Realms, you guys are talented, every screenshot and video is expertly done and looks ... : dancingpolkabear
By: Downforce x Show Full Postmust be regarding another round of funding for... something.
I don't even think this type of media can/should be leaked with the litigation still pending, correct?Nov 30, 2009 4:25pm PST
By: higround x Show Full PostIf this whole farce (this shot and all the crap before) turns out to be the most elaborate marketing campaign ever, will you be happy or just pissed off?Nov 30, 2009 8:30am PSTIf this whole farce (this shot and all the crap before) turns out to be the most elaborate marketing camp... : higround
Thread Truncated. Click to see all 12 replies.
It's not a farce and it's not a marketing campaign. People did, in fact, lose their jobs a few months a... : TickHeadDog
its the brett favre of games. : mindshot
Worst marketing campaign ever : Sothebys
By: gooblerampling x Show Full PostSeriously? I realize that Broussard posts here but please stop reporting news on this ridiculous farce. Studios like 3DRealms are one of the great examples of why video game development (and video games collectively) have a long way to go.Nov 30, 2009 6:10am PSTSeriously? I realize that Broussard posts here but please stop reporting news on this ridiculous farce. S... : gooblerampling
Thread Truncated. Click to see all 7 replies.
*cough* ShackNEWS is a NEWS site. Video game news site reports video game news! Special report at 11! ... : unholydonuts
Seriously! : cdbeckman
why so? : cdbeckman
By: capt tripps x Show Full PostDuke Nukem - Episode 1 would be niceNov 30, 2009 3:37pm PSTDuke Nukem - Episode 1 would be nice : capt tripps
By: diggywiddit x Show Full PostThe only way I'm taking anything Duke related seriously is if 3DR actually sells all Duke property and IP to another developer who was actually capable of finishing and shipping a game...otherwise its all cigar smoke and mirrors..Nov 30, 2009 2:45pm PST
By: fw_rams x Show Full Postso.......are the major stores taking preorders again? ;)Nov 30, 2009 2:04pm PST
By: Godhatesfatpeople x Show Full Posthaha, and so it begins. AGAIN!Nov 30, 2009 2:04pm PSThaha, and so it begins. AGAIN! : Godhatesfatpeople
By: X-GOUKI x Show Full Postdidn't ya'll go thru this already?
a screenshot is leaked and it makes it to the front page, then ppl get their hopes up again for nothing.
Nov 30, 2009 1:40pm PST
By: inf3d3l x Show Full PostWhy even bother with this crap. Unless they actually release a NEW game, then make it news worthy.
I don't care to see shots of things that practically don't exist.Nov 30, 2009 12:05pm PST
By: David Craddock x Show Full PostWhether this is concerning DNF, DNF under a new name (probably the best course of action at this point), or a completely new Duke, fine. But it would be a tremendously awful idea to tease or announce ANYTHING too early this time. Don't get me wrong: I am intrigued! But seriously, bide your time, 3DR.Nov 30, 2009 8:40am PSTWhether this is concerning DNF, DNF under a new name (probably the best course of action at this point), ... : David Craddock
By: matthaeus x Show Full PostThese screenshot has been part of the leaked gameplay footage, see here (2:15 - 2:35): http://www.youtube.com/watch?v=VRnv_tFKStQ
Maybe the soldier in the screenshot gets killed before Duke (the player) enters the scene (as seen in the video).Nov 30, 2009 7:04am PSTThese screenshot has been part of the leaked gameplay footage, see here (2:15 - 2:35): http://www.youtube... : matthaeus
By: Unkei x Show Full Postwhatever.Nov 30, 2009 10:48am PSTwhatever. : Unkei
By: GodFather x Show Full Postthe whole thing is the biggest joke in entertainment history!Nov 30, 2009 10:44am PST
By: ajvitaly x Show Full PostThe only way I can get excited about Duke now is if they were to say DNF is back to full development and will be released this year.Nov 30, 2009 6:06am PSTThe only way I can get excited about Duke now is if they were to say DNF is back to full development and ... : ajvitaly
By: DutchAzlon x Show Full PostOh come on guys you all know that in an alternate Universe Duke has already be bagged,tagged and played!Nov 30, 2009 10:14am PST
By: jkstanton x Show Full PostEverything 3DR does feels like a slimy scheme.Nov 30, 2009 6:02am PST
By: ShXIII x Show Full PostKnowing 3DRealms and there bullshit track record I can almost guarantee this is nothing DNF related, but yet another remake of a remake of a remake and most likely a super duper rehashed version of DN3D that will work on any new Timex Watch.
I have no faith in 3DR. The only thing they are "good" at is re-releasing the same DN3D game over and over again on different platforms.
Take your Hype train 3DR and shove it right up your arrogant asses!!Nov 30, 2009 10:06am PST
By: manlyman x Show Full PostThe art direction and game engine looks too familiar to the leaked DNF footage and screens. And there's no way that this is running on a portable console. Looks like there may have been some progress in the 3D Realms vs. Take2 court battle and that we may see DNF soon. Fuck yeah!Nov 30, 2009 6:21am PSTThe art direction and game engine looks too familiar to the leaked DNF footage and screens. And there's ... : manlyman
By: stgdz x Show Full PostI saw this and the PA comic about tribes came to my mind
http://www.penny-arcade.com/images/2002/20021213l.gifNov 30, 2009 6:04am PSTI saw this and the PA comic about tribes came to my mind http://www.penny-arcade.com/images/2002/2002121... : stgdz
By: spinx2 x Show Full Postalways bet on duke!Nov 30, 2009 9:28am PSTalways bet on duke! : spinx2
By: the archvile x Show Full PostMOVE ON... MOVE ON... MOVE ON... MOVE ON...Nov 30, 2009 9:08am PSTMOVE ON... MOVE ON... MOVE ON... MOVE ON... : the archvile
By: scener x Show Full Post3D Realms have only themselves to blame for ruining the Duke Nukem franchise.Nov 30, 2009 8:44am PST
By: donjuancarlos x Show Full PostDuke Nukem: Soap Opera for gamers.
As the sands of time...Nov 30, 2009 8:41am PST
By: veras x Show Full PostDUUUUUUUUUUUUUUUUUKENov 30, 2009 6:02am PSTDUUUUUUUUUUUUUUUUUKE : veras
By: limabone-jlp x Show Full PostThat takes cojones to do something like this after all the BS we have been subjected to over the years....this is not endearing me.Nov 30, 2009 8:28am PST
By: Schnapple x Show Full PostHere's the thing:
If this is a DNF teaser then I'm having a hard time figuring out what the announcement is.
Do they have a ship date for DNF? If so then how can they since the game wasn't finished and the dev team was fired? If it was nearly finished then what was taking so long?
Are they going to announce it's coming soon? Yeah - it's not like we haven't heard that before.
Could it be an announcement of the lawsuits being resolved, the funding has returned, and the hiring has commenced? Great - so while you go find a bunch of people to work on it and get them up to speed (since the odds are a number of the people you've fired have been hired elsewhere by now) it will take even more years to get done.
The only thing I can think of, DNF-related, which would make any sense is that they've teamed up with some other studio, like Gearbox, to polish off the last of it and get it out the door.Nov 30, 2009 8:20am PST
By: Sothebys x Show Full Postrofl at these comments.
My how the mighty have fallen.Nov 30, 2009 8:20am PST
By: retarded talking dinosaur x Show Full PostLet's just put a lid on Duke. It was a decent game 13 years ago that that's it. Game over. Hope you enjoyed that one. Until anything is on the shelves and critically acclaimed I am officially COMPLETELY DISINTERESTED with this franchise.Nov 30, 2009 8:02am PST
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This is a 100% whole wheat crust that I allowed to slow rise overnight. I also make a loaf of bread with the same dough. It was topped with a swiss cheese sauce, lentils, sauerkraut, onions, 1000 island dressing and raw kale and carrots. Super delicious! I always pre-bake my crust for around 5 minutes or so before adding any toppings. I sprayed the crust with olive oil cooking spray and added garlic powder and caraway seeds to it for a more authentic flavor.
More collard wraps. For those of you wondering, I eat mine raw. You can easily blanch or steam your wraps if the raw taste is too much. This was a combo raw wrap with a little bit of cooked filling. I used a teeny bit of refried beans and some cooked cheese sauce, a raw burger which I cut up into slices, pickled jalapenos, tomato, onion, cilantro and 1/4 an avocado.
The raw burger was made from sunflower seeds, carrots, raw bbq sauce and chipotle powder.
I am going to ignore the fact that collards and kale rate high on the pesticide list. It seems that no matter what we do, we are screwed. Seriously. If I had a ton of money to spend, I would buy organic. I don't and I am doing the best I can to get the most nutrition for my buck! I find it so easy to fall into this trap of worrying so much about this or that and it is not productive for my sanity!
For those of you who ask me over and over why I don't grow my own food. (This has to be the number one question people email me about!) I live in a basement apartment in New Hampshire surrounded by pine trees. I do not have a patio. I do not have enough light inside to do so. I wish I could.
I wonder if I could find someone with land who would be willing to work something out landwise? Hmmm.. I'm going to check into that! I could cook food for the person or give them part of my crop in exchange for their land? It's worth a try.
I've noticed several things that have changed shopping wise. I am no longer buying organic baby spinach and arugula. For around $2.99 for 5 oz, it is still a decent deal, but I can get some large bunches of kale and collards for $1.29. The kale and collards have more versatility and a much longer shelf life. I can use them in green smoothies, as salads, as sturdy greens, in soups and wraps. Also, they are very filling and have pretty high amounts of protein. 4 cups of raw kale has 8.8 grams of protein as opposed to 3.4 grams in spinach. Add 1/2 cup of beans, a healthy dressing and a T of nutritional yeast and I have a huge, satisfying salad that has around 22 grams of protein!
I have not bought any bread. Not even when it's on sale.
I haven't bought tofu either.
I keep putting off making tofu! You have to have 3 pitchers full of soymilk, which is a total PITA... but I can't wait to give it a try! I miss tofu. In fact, that's what I miss the most... oh and processed vegan cheese! I really want to try some of the new FYH out there. I hear they've really improved the flavor and meltability. I've been making a lot of cheese sauces and while they're good, sometimes I just want the store bought stuff.
Yo Vegan Cheese companies! Send me samples! PRETTY PLEASE!!!
All right.. back to food!
One last VERY exciting thing.. my electric bill was only $24.17 last month! That's for heat and electricity! (I don't pay for hot water).. Granted, I did spend 5 days at my old house, but I think unplugging everything and obviously hardly ever using my heat has really payed off! My house is a balmy 62 degrees right now! My son is home sick, so I turned the heat on.


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In previous posts we have called attention to problems associated with hearing loss such as the onset of feelings of isolation, depression and dementia. Recent medical research has discovered a correlation between cardiovascular systems and hearing health.
In an article dated September 19, 2013 The Better Hearing Institute (BHI) of Washington D.C. says the following:
Gen Xers and baby boomers should no longer ignore their hearing loss, says the Better Hearing Institute (BHI), which is raising awareness of the link between cardiovascular and hearing health in recognition of World Heart Day on September 29th. A growing body of research shows that a persons hearing health and cardiovascular health frequently correspond. And because the jury is still out on exactly why there is a connection and which comes first, it behooves those 40 and older to get their hearing tested as a routine part of their medical care. The vast majority of people with hearing loss can benefit from hearing aids, which have been shown to improve quality of life.
How are hearing loss and heart disease connected? The inner ear is one of the most sensitive parts of the body and very dependent upon proper blood flow to operate efficiently. In the same article BHI cites the following:
Studies have shown that a healthy cardiovascular systema persons heart, arteries, and veinshas a positive effect on hearing. Conversely, inadequate blood flow and trauma to the blood vessels of the inner ear can contribute to hearing loss.
David R. Friedland, MD, PhD, Professor and Vice-Chair of Otolaryngology and Communication Sciences at the Medical College of Wisconsin in Milwaukee, has been studying the relationship between cardiovascular and hearing health for years. He offers up this response:
The inner ear is so sensitive to blood flow that it is possible that abnormalities in the cardiovascular system could be noted here earlier than in other less sensitive parts of the body.
In one study, published in The Laryngoscope, Dr. Friedland and fellow researchers found that audiogram pattern correlates strongly with cerebrovascular and peripheral arterial disease and may represent a screening test for those at risk. They even concluded that patients with low-frequency hearing loss should be regarded as at risk for cardiovascular events, and appropriate referrals should be considered.
There is more evidence to support the conclusion. The BHI goes on to say,
Other evidence exists. In fact, the authors of a study published in the American Journal of Audiology concluded that the negative influence of impaired cardiovascular health on both the peripheral and central auditory system and the potential positive influence of improved cardiovascular health on these same system shave been found through a sizable body of research conducted over more than six decades.
So in other words a healthy heart can help maintain healthy hearing. If you have a hearing loss it could be a sign of an unhealthy heart so get your hearing tested today .
By Susan L. Fenrich, BC-HIS, Licensed Hearing Instrument Specialist, Board Certified in Hearing Instrument Sciences
The content at Welsch Hearing Aid Company blog entries, print media and websites, including text, graphics, images, opinions, or information obtained from links, is provided for informational purposes only. This content should not be considered by anyone as a substitute for medical or other hearing health professional diagnosis, treatment, advice, or recommendations.


text: Item Loose Bicone 9/7mm : HurriCane Glass - Dakota Plaid (VLH-13-LK050) is in the Factory Overstock category. You can find similar items on the Loose HurriCane Glass Beads by the Kilo! group page. As with all of our beads this item is manufactured to be the highest quality and would be a great addition to your bead store. We sell this item to stores by the Kilo, and it is 0 in size.Please note that we now have many resources for bead stores such as information about industry standard units and the manufacturing process. There are also sections about glass cane and finishes/coatings used for beads.Other Images:You may wish to see other beads that are: 9/7mm Bicone Dakota Glass HurriCane Loose Plaid


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Take Action
Ask your Member of Congress to visit a food bank
Each day, hunger is experienced in every community across this country. In fact, our network feeds over 37 million neighbors each year. Get involved today and tell your Members of Congress to visit a food bank so they understand what hunger looks like in their community.
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Demonstrate Your Values
If you believe that no one should go hungry in America, join the Hunger Action Center.
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Learn more about Feeding America's work to pass policies that help Americans struggling with hunger.


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Aerosmith Maps Out Second Leg Of 'Global Warming' Tour
Wednesday, September 19, 2012
Aerosmith has announced the dates and venues for the second leg of its Global Warming Tour, which will kick off on November 8th in Oklahoma City and hit 13 more cities before wrapping up on December 13th in Nashville. The band will be touring behind its 15th studio album, Music From Another Dimension, which arrives on November 6th. Support on the tour will come from Cheap Trick.
Tickets go on sale for the tour next Monday (September 24th) at 10:00 a.m. local time through Live Nation. Pre-sales for certain credit card holders and members of Facebook begin this Wednesday (September 19th) and Friday (September 21st) respectively.
Music From Another Dimension is Aerosmith's first collection of all-new music in 11 years and features the singles "What Could Have Been Love" and "Lover A Lot." A track called "Freedom Fighter" features a guest appearance from Johnny Depp on vocals.
Newly confirmed Aerosmith tour dates (subject to change):
November 8 - Oklahoma City, OK - Chesapeake Energy Arena
November 11 - Wichita, KS - INTRUST Bank Arena
November 14 - Kansas City, MO - Spring Center
November 16 - Austin, TX - Frank Erwin Center
November 20 - New York, NY - Madison Square Garden
November 23 - Atlantic City, NJ - Revel Resorts - Ovation Hall
November 25 - Columbus, OH - Nationwide Arena
November 27 - Toronto, ON - Air Canada Centre
December 1 - Las Vegas, NV - MGM Grand Garden Arena
December 3 - Los Angeles, CA - STAPLES Center
December 6 - New Orleans, LA - New Orleans Arena
December 9 - Fort Lauderdale, FL - BB&T Center
December 11 - Tampa, FL - Tampa Bay Times Forum
December 13 - Nashville, TN - Bridgestone Arena
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As more and more snow piles up around metro Detroit, the more difficult it's becoming to find salt.Not the kind used to help clean major roadways. But instead the kind used to keep your walkways clear and business entrances dry.Residents are finding store shelves depleted of rock salt and products like Ice Melt."It's been tough for us to get salt," said Rob Williams from the Lowe's Home Improvement store in Southfield. "We're working with our suppliers to get ourselves replenished."As of Feb. 5, this winter ranked as Detroit's seventh snowiest in recorded history with nearly 70 inches of snow.Alternatives like water softener salts can still be used around the driveway, FOX 2's Roop Raj reports.Note: Raj made calls around town and did find several stores, including Miller's at 13636 W. Seven Mile in Detroit and Carefree Lawn Center at 2805 Van Horn in Trenton, with a full stock of rock salt.
25 FOX DriveDedham, MA 02026
Phone (781) 467-2525


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Prices and availability are subject to change from the time and date that you print this page.
10/2/2014 12:41:14 PM. For Customer Service, please call 800.933.9904
I think I can organize the playroom. I think I can clean up the bedroom. I think I can straighten the closet. Well, now you can. Our canvas hampers are easy on the eyes and come in 6 great colors.
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Wise Camo High-Back Fold-Down Boat Seats
Indestructible injection molded plastic frame is totally weatherproof to the elements. Strong aluminum hinges. High compression, high density, polyurethane foam padding is covered with moisture barrier. 500 denier cordura fabric is soft and non-reflective and loaded with plenty of mildew and UV inhibitors. T-Nut construction to mount on any 4-bolt BIA standard mounting system. Mounting bolts included.
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