“This study demonstrates that MDS is a very common blood cancer of the elderly, and that those who have it are at high risk of dying prematurely from other causes,” says lead author Stuart L. Goldberg, M.D., a hematologist/oncologist who is Chief of the Division of Leukemia, John Theurer Cancer Center. “This has implications for how the disease is treated and will hopefully spur additional research.”

Myelodysplastic syndromes, which occur primarily in people age 60 and above, are a group of diseases in which the bone marrow does not make enough healthy blood cells. Patients with MDS are more prone to infection, anemia and bleeding and often report extreme fatigue and other debilitating symptoms. The most common treatment for MDS is blood transfusion, but four new medications to treat the disease and its complications have come to the market in the last four years. MDS is diagnosed through blood and bone marrow tests.

“Dr. Goldberg’s study highlights the breadth of work we are completing at the John Theurer Cancer Center where we are committed to improving patient care through advancing research,” said Andrew L. Pecora, M.D., F.A.C.P., C.P.E., Chairman and Executive Administrative Director, John Theurer Cancer Center. “We are pleased to take a leading role in this milestone study for the MDS community.”

MDS was not reportable as a cancer until 2001, when the National Cancer Institute (NCI) began requiring that all tumor registries report cases to the Institute’s Surveillance, Epidemiology & End Results (SEER) program. The SEER database reported 10,300 newly diagnosed MDS patients in 2003, with a three-year survival rate of just 35 percent.

To conduct a “head-to-head” study, Dr. Goldberg and colleagues analyzed claims data for Medicare beneficiaries age 65+ for 2003. What they found was alarming: an estimated 45,000 new cases of MDS.

The gap in estimates can be explained by differing data sources: Medicare data are submitted by both physicians in private practice as well as hospital-based physicians, while SEER data come strictly from tumor registries, which are primarily found in hospitals.

“MDS is generally treated by hematologists and primary care physicians in private practice, and elderly patients with MDS are frequently not seen at a hospital-based cancer center until their disease progresses,” says Dr. Goldberg. “So most cases are not being reported to NCI. As we found in our study, many apparently die of other causes as their disease progresses.”

The researchers found a much higher incidence of other serious illnesses among MDS patients than among American seniors as a whole. More than 73% of MDS patients experienced a heart attack within three years of diagnosis, while 54.5% of the general Medicare population did. The prevalence of other conditions was also higher, including: diabetes (40% for MDS patients, vs. 33.1% non-MDS); dyspnea, a type of shortness of breath (49.4% vs. 28.5%); liver disease (.8% vs. .2%); and sepsis, a serious blood infection (22.5% vs. 6.1%). MDS patients requiring blood transfusions had a higher incidence of these conditions than those who were not transfused.

Acute myeloid leukemia (AML) developed within three years in 9.6% of newly diagnosed MDS patients, and those who received transfusions progressed to AML at a rate of 24.6% (previous estimates were that 20-30% of MDS patients progressed to AML).

A much higher percentage of MDS patients died during the study period than those without MDS. The three-year survival rate for those with MDS was 60%, while it was 84.7% for the general Medicare population. The mortality rate for transfused MDS patients was higher than for those not transfused. The higher survival rates in this study compared to SEER were attributed to the higher percentage of early stage patients treated in communities compared to hospital-based tumor registries.

While the health consequences and scope of the disease found in the study were alarming, the cost of treating MDS also proved to be significant. In 2003, the median amount billed to Medicare for MDS was $16,181, compared to $1,575 for Medicare beneficiaries as a whole.

“As the U.S. population continues to age, MDS will become a more prominent medical problem with a significant impact on the affordable health insurance system,” says Dr. Goldberg.

Dr. Goldberg believes that this study will provide a baseline for additional research. “Since we now know the scope of the problem as it was before MDS medications became available, it will be interesting to see in future studies how new cancer treatments have impacted the disease. We also need to learn why MDS patients develop other conditions, such as heart failure, so that we can treat the whole person.”

As the country endures the highest unemployment rates in decades, the recent economic stimulus (American Recovery and Reinvestment Act) made $7 billion available to be split among state unemployment insurance programs if they adopt certain measures to increase eligibility.

H. Luke Shaefer, assistant professor at the U-M School of Social Work, said these measures, among other things, would allow workers to include recent earnings in their eligibility calculations, expand eligibility to those who quit for “compelling family reasons” such as domestic violence, and enhance eligibility of part-time workers.

These provisions, however, do not go far enough in helping all workers gain access to the program, Shaefer says.

Shaefer used longitudinal data from the 2001 panel of the Survey of Income and Program Participation to compare eligibility and participation rates in unemployment insurance among vulnerable workers with those of more advantaged workers. He focused on low-wage workers and part-time workers who were primary wage earnersa particularly disadvantaged group.

Shaefer found that a large majority of vulnerable workers already met earnings requirements, a main component targeted by the economic stimulus reforms. About four out of five vulnerable unemployed workers met their state’s earnings requirements, but only 17 percent of them received benefits.

Another barrier involved low rates of nonmonetary eligibility related to the reason for job loss, according to Shaefer. This is at least in part driven by the clustering of vulnerable workers in industries like retail, where firms tend to avoid layoffs by reducing worker hours and cutting labor costs in other ways, he says. In most cases, a worker must have been laid off to be eligible for unemployment insurance.

One of the study’s key findings was that differences in eligibility do not fully explain the disparity between vulnerable and advantaged workers. Even among the lowest-wage workers whom Shaefer estimates are eligible, only 50 percent reported receiving benefits. The same was true of 77 percent of high-wage workers.

“If the federal government and states want to bring vulnerable workers into the system, they may need to explore ways to notify workers of their possible eligibility and will need to think creatively about covering workers clustered in industries that avoid layoffs by cutting workers’ hours,” Shaefer said. “The provisions in the ARRA are a step in the right direction. However, more is needed to truly cover vulnerable workers.”

The findings appear in the current issue of Journal of Social Policy.

Radiation therapy is used to kill cancer cells and shrink tumors. But because radiation also damages normal cells, doctors must limit the dose. Melanin, the naturally occurring pigment that gives skin and hair its color, helps shield the skin from the damaging effects of sunlight and has been shown to protect against radiation.

“A technique for shielding normal cells from radiation damage would allow doctors to administer higher doses of radiation to tumors, making the treatment more effective,” said Ekaterina Dadachova, Ph.D., associate professor of nuclear medicine and of microbiology & immunology and the Sylvia and Robert S. Olnick Faculty Scholar in Cancer Research at Einstein, as well as senior author of the study.

In previously published research, Dr. Dadachova and colleagues showed that melanin protects against radiation by helping prevent the formation of free radicals, which cause DNA damage, and by scavenging the free radicals that do form.

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Ekarerina Dadachova, Ph.D., discusses her new research on melanized nanoparticles and how they protect bone marrow from the negative side effects of radiation therapy. Dr. Dadachova is associate professor of nuclear medicine and of microbiology and immunology and the Sylvia and Robert S. Olnick Faculty Scholar in Cancer Research at Albert Einstein College of Medicine Credit: Albert Einstein College of Medicine

“We wanted to devise a way to provide protective melanin to the bone marrow,” said Dr. Dadachova. “That’s where blood is formed, and the bone-marrow stem cells that produce blood cells are extremely susceptible to the damaging effects of radiation.”

Dr. Dadachova and her colleagues focused on packaging melanin in particles so small that they would not get trapped by the lungs, liver or spleen. They created “melanin nanoparticles” by coating tiny (20 nanometers in diameter) silica (sand) particles with several layers of melanin pigment that they synthesized in their laboratory.

The researchers found that these particles successfully lodged in bone marrow after being injected into mice. Then, in a series of experiments, they investigated whether their nanoparticles would protect the bone marrow of mice treated with two types of radiation.

In the first experiment, one group of mice was injected with nanoparticles and a second group was not. Three hours later, both groups were exposed to whole-body radiation. For the next 30 days, the researchers monitored the blood of the mice, looking for signs of bone marrow damage such as decreased numbers of white blood cells and platelets.

Compared with the control group, those receiving melanin nanoparticles before radiation exposure fared much better; their levels of white cells and platelets dropped much less precipitously. Ten days after irradiation, for example, platelet levels had fallen by only 10 percent in mice that had received nanoparticles compared with a 60 percent decline in untreated mice. Furthermore, levels of white blood cells and platelets returned to normal much more quickly than in the control mice.

A second experiment assessed not only bone-marrow protection but whether the nanoparticles might have the undesirable effect of infiltrating and protecting tumors being targeted with radiation. Two groups of mice were injected with melanoma cells that formed melanoma tumors. After one group of mice was injected with melanin nanoparticles, both groups received an experimental radiation treatment designed by Dr. Dadachova and her colleagues specifically for treating melanoma.

This treatment uses a radiation-emitting isotope “piggybacked” onto an antibody that binds to melanin. When injected into the bloodstream, the antibodies latch onto the free melanin particles released by cells within melanoma tumors. Their isotopes then emit radiation that kills nearby melanoma tumor cells.

Following the second experiment, the melanoma tumors shrank significantly and to the same extent in both groups of mice – indicating that the melanized nanoparticles did not interfere with the radiation therapy’s effectiveness. And once again, the melanized nanoparticles prevented radiation-induced bone-marrow damage: between the third and seventh day after the antibody-isotope radiation therapy was administered, mice injected with nanoparticles experienced a drop in white cells that was significantly less than occurred in mice not pre-treated with nanoparticles.

“The ability to protect the bone marrow will allow physicians to use more extensive cancer-killing radiation therapies and this will hopefully translate into greater tumor response rates,” said Arturo Casadevall, M.D., Ph.D., professor of medicine and of microbiology & immunology, the Leo and Julia Forchheimer Chair in Microbiology & Immunology, and a co-author of the study.

Some nanoparticles could still be found in bone marrow 24 hours after their injection, which shouldn’t pose a problem. “Since the nanoparticles are rapidly removed by phagocytic cells, they’re unlikely to damage the bone marrow,” said Dr. Dadachova. “We didn’t detect any side effects associated with administering the particles.”

“These results are encouraging for other potential applications of melanin, including radioprotection of other radiation-sensitive tissues, such as the gastrointestinal tract,” noted Andrew Schweitzer, M.D., formerly a Howard Hughes Medical Institute fellow at Einstein and lead author of the study.

Clinical trials testing whether melanized nanoparticles might protect cancer patients undergoing radiation therapy could begin in two to three years, Dr. Dadachova predicted. She also noted that melanized nanoparticles might also have other applications, such as protecting workers charged with cleaning up nuclear accidents, protecting astronauts against radiation exposure in space, or even protecting people following a nuclear attack.

In 2005, California approved a law banning the sale and rental of violent video games to children under the age of 18, and ordered game makers to post explicit warnings on such games.

The law was quickly challenged, and was overturned by a lower federal court and again on appeal in February 2009 on grounds that it restricted freedom of expression.

California Governor Arnold Schwarzenegger has now appealed the case to the Supreme Court, which next month will take up the case, known as “Schwarzenegger v. Entertainment Merchants Association.”

The law defines a violent video game as one that depicts “killing, maiming, dismembering, or sexually assaulting an image of a human being,” though it does not prevent a parent or guardian from purchasing the game for their child.

In their submission to the court, attorneys for the state of California said the ban was based on medical and sociological studies that “establish a correlation between violent video game play and increased automatic aggressiveness, aggressive thoughts and behavior, antisocial behavior, and desensitization to violence in minors and adults.”

At least nine other states and localities have enacted similar restrictions, including Washington, Minnesota and Illinois. In California, retailers are subject to 1,000 dollars in fines for each violation.

The Video Software Dealers Association, which brought the case before the Supreme Court, argues that minors should have the same access to potentially violent video games as they currently do to movies or books with similarly graphic content.

The closely watched free-speech case is expected to be among the first heard by the newest Supreme Court justice who is expected to join the court by the start of the new term in October, replacing retiring Justice John Paul Stevens.

Earlier this month, the Supreme Court cited free speech protections in overturning a law banning images of animal cruelty, reversing a sentence against a man who sold videos of pitbull dog fights that he had not himself organized.

The drop is estimated to have occurred some 137 million years ago during a time when dinosaurs roamed the Earth, and would have seen the islands fall from an average of 13 degrees centigrade (ocean temperature) to as low as four degrees.

The findings, which were published in the journal Geology and featured as a highlight in Nature Geoscience, will further contribute to the debate over climate change as they appear to contradict the common model which links high levels of Carbon Dioxide (CO2) – as recorded in the Cretaceous era – with reduced polar ice caps.

Despite being located in the Arctic Circle, Svalbard was home to numerous species of dinosaur and was typically characterised by warm, shallow seas and swamps.

But the research team, led by Dr Gregory Price of the University of Plymouth, found evidence in fossils and carbonate materials preserved in marine rocks in the region of a transient shift to cooler glacial conditions around 137 million years ago.

Dr Price said: “At certain times in the geological past, the world has been dominated by greenhouse conditions with elevated CO2 levels and warm Polar Regions, and hence, these are seen as analogues of future global climate.

But this research suggests that for short periods of time the Earth plunged back to colder temperatures, which not only poses interesting questions in terms of how the dinosaurs might have coped, but also over the nature of climate change itself.

Dr Price, along with Dr Elizabeth Nunn, of Johannes Gutenburg Universitat in Mainz, Germany, first visited Svalbard in 2005 to collect fossils and samples, in an area famed for a number of paleontological discoveries, including giant marine reptiles such as pliosaurs and icthyosaurs.

The samples were analysed back in Plymouth and prompted return trips to the area to gather more evidence.

The flourishing of the dinosaurs and a range of other data indicates that the Cretaceous period was considerably warmer and boasted a high degree of CO2 in the atmosphere, said Dr Price.

But over a period of a few hundred or a few thousand years, ocean temperatures fell from an average of 13 degrees centigrade to between eight and four degrees.

Although a short episode of cool polar conditions is potentially at odds with a high CO2 world, our data demonstrates the variability of climate over long timescales.

Rethink drink because some of drinks have CO2.