The New York Times, May 29, 2013, by Sabrina Tavernise — Immigrants have contributed billions of dollars more to Medicare in recent years than the program has paid out on their behalf, according to a new study, a pattern that goes against the notion that immigrants are a drain on federal health care spending.
The study, led by researchers at Harvard Medical School, measured immigrants’ contributions to the part of Medicare that pays for hospital care, a trust fund that accounts for nearly half of the federal program’s revenue. It found that immigrants generated surpluses totaling $115 billion from 2002 to 2009. In comparison, the American-born population incurred a deficit of $28 billion over the same period.
The findings shed light what demographers have long known: Immigrants are crucial in balancing the age structure of American society, providing an infusion of young, working-age adults who support the country’s aging population and help cover the costs of Medicare and Social Security. And with the largest generation in the United States, the baby boomers, now starting to retire, the financial help from immigrants has never been more needed, experts said.
Individual immigrant contributions were roughly the same as those of American citizens, the study found, but immigrants as a group received less than they paid in, largely because they were younger on average than the American-born population and fewer of them were old enough to be eligible for benefits. The median age of Hispanics, whose foreign-born contingent is by far the largest immigrant group, is 27, according to the Brookings Institution. The median age of whites in the United States is 42.
The study, which was published on the Web site of the journal Health Affairs on Wednesday, comes as Congress considers legislation that would eventually give legal status to the country’s 11 million unauthorized immigrants. The legislation has sparked a vigorous debate about whether immigrants ultimately contribute more than they receive from the federal budget. One of the sticking points has been whether immigrants should be eligible for government programs, including health benefits, before they qualify for citizenship, but while they are on the path to getting it.
The study was concerned only with Medicare, the federal program that accounts for about a fifth of all American health care expenditures. Experts said that the study’s findings served as a useful reminder that immigrants, at least for now, are extending the life of the beleaguered program, not hastening its demise.
“There’s this strong belief that immigrants are takers,” said Leighton Ku, the director of the Center for Health Policy Research at George Washington University. “This shows they are contributing hugely. Without immigrants, the Medicare trust fund would be in trouble sooner.” The belief prevails, for example, among some opponents of immigration reform.
The study did not grapple with the health care costs of immigrants over their full lifetimes, a calculation that economists say is critical to understanding their long-term impact on the federal budget.
“It’s just a snapshot of a point in time,” said Paul Van de Water, a visiting fellow at the liberal-leaning Center on Budget and Policy Priorities.
The study drew on two nationally representative federal surveys from the Census Bureau and the Department of Health and Human Services. Researchers included the contributions of legal residents who were not citizens, a group that is eligible for Medicare if certain requirements are met; unauthorized immigrants; and citizens who were born abroad.
It was not clear how much of the surplus was made up of earnings by immigrants in the country illegally, who are ineligible for most government programs.
The finding “pokes a hole in the widespread assumption that immigrants drain U.S. health care spending dollars,” said Leah Zallman, an instructor of medicine at Harvard Medical School and the lead author of the study.
Similar calculations have been made for Social Security. The chief actuary of the Social Security Administration, Stephen C. Goss, estimated that immigrants in the country illegally, some of whom assume fake Social Security numbers to provide cover for employers, generated a surplus of about $12 billion for the Social Security Trust Fund in 2010.
But that equation would change if unauthorized immigrants were to gain legal status under a new law and eventually began collecting Social Security once they were of retirement age. One major policy question is how much that might cost, experts said.
The Heritage Foundation, a conservative institute, estimated that the legislation’s changes, if implemented, could cost taxpayers more than $6 trillion. Critics of that calculation said it did not take into account the economic benefits that would arise from taking millions of people out of the shadow economy.
Mr. Goss, in a letter this month to Senator Marco Rubio, a Florida Republican, said that the legislation’s effect on the long-term health of Social Security would be positive in the long term.
Immigrants tend to be healthier than American-born citizens, and have lower mortality rates, research has found. Dr. Ku said there was evidence that individual immigrants actually use less health care than native-born Americans. He has calculated, for example, that immigrants’ medical costs were 14 percent to 20 percent less than those who were born in the United States, even after controlling for other factors such as emergency room visits and insurance coverage, which fewer immigrants have.
The study found that average expenditures among immigrant Medicare enrollees in 2009 were $3,923, lower than the average $5,388 expenditure among the American-born. The difference, however, was just shy of statistical significance, because of wide variations in medical expenditures and the small numbers of immigrant enrollees, which made the study’s margin of error wide.
Robert Rector, a senior research fellow at the Heritage Foundation, who is an author of the institute’s report earlier this month, said that looking at Medicare alone was not very useful, as it was just one slice of the entire entitlement pie. And the large immigrant youth population, which the study spends most of its time on, is familiar, he said.
“It’s a yawner of a study,” he said. “Young people don’t get Medicare. We don’t need several Ph.D.s to tell us that.”
Others defended the findings, saying that they showed immigrants were helping prop up the country’s retirement funds at the critical point when baby boomers were starting to retire.
“They’ll be paying into the system at the very time it is most strained,” said Patrick Oakford, a researcher on economic and immigration policy at the Center for American Progress, a liberal-leaning institute. He estimated that the average undocumented immigrant was 34 and therefore would not retire until 2046.
2 Skin Cancer Drugs Win FDA Approval
By John Gever, Deputy Managing Editor, MedPage Today
MedPageToday.com, May 30, 2013, by John Gever, WASHINGTON — Two new drugs for metastatic or inoperable melanoma, dabrafenib (Tafinlar) and trametinib (Mekinist), were approved by the FDA on Wednesday.
The agency also approved a companion diagnostic test for both agents to detect certain mutations in the BRAF gene that render melanoma cells susceptible to the drugs.
Dabrafenib is an inhibitor of the BRAF gene when it carries the so-called V600E mutation. Trametinib inhibits a target known as MEK and is effective primarily against melanomas carrying either the V600E or V600K mutations.
Approximately half of patients with malignant melanoma are marked by BRAF mutations, the FDA said.
The agency noted that dabrafenib and trametinib were approved separately as stand-alone drugs, not as a combination, although therapy with both drugs together has been tested clinically and appeared to be better than dabrafenib alone.
The diagnostic product, called the THxID BRAF test, was evaluated in the same clinical trials supporting the two drugs’ approvals. It was used to select patients for the trials.
Dabrafenib’s approval was based primarily on a trial in 250 patients randomized to the drug or a standard chemotherapy agent, dacarbazine. The BRAF inhibitor prolonged progression-free survival by 2.4 months, the FDA said.
Trametinib’s pivotal trial involved 322 patients with a chemotherapy regimen as the comparator. Progression-free survival was extended by 3.3 months with trametinib. However, patients previously treated with other BRAF inhibitors, including dabrafenib, did not benefit from trametinib, according to the FDA.
Both drugs had a variety of side effects. For dabrafenib, these included hyperkeratosis, headache, fever, arthralgia, alopecia, hand-foot syndrome, and noncancerous skin lesions. More seriously but less commonly, some patients experienced cutaneous squamous cell carcinomas, hypotensive fever, dehydration, rigors, kidney failure, and hyperglycemia that sometimes required initiation of anti-diabetic drugs.
Adverse effects seen with trametinib included heart failure, pulmonary inflammation, skin infections, and vision loss, as well as less serious effects such as rash, diarrhea, peripheral edema, and acne-like skin eruptions.
Both of the new agents are manufactured by GlaxoSmithKline. The BRAF mutation test is sold by bioMerieux.
Uncredited/Health Protection Agency, via Associated Press: An image of a coronavirus, part of a family that causes the common cold and SARS. A new strain, called MERS, for Middle East respiratory syndrome, has been particularly lethal, killing half those infected.
A man in Saudi Arabia wore a mask last week to protect against a virus that has killed 22 since it was found there last year.
The New York Times, May 29, 2013, by Donald G. McNeil Jr. — A new flu, H7N9, has killed 36 people since it was first found in China two months ago. A new virus from the SARS family has killed 22 people since it was found on the Arabian Peninsula last summer.
In past years, this might have been occasion for panic. Yet chicken and pork sales have not plummeted, as they did during flus linked to swine and birds. Travel to Shanghai or Mecca has not been curtailed, nor have there been alarmist calls to close national borders.
Is this relatively calm response in order? Or does the simultaneous emergence of two new diseases suggest something more dire?
Actually, experts say, the answer to both questions may well be yes.
“We’ve done a great job globally in the last 10 years,” said Dr. William B. Karesh, a wildlife veterinarian and chief of health policy for the EcoHealth Alliance, which tracks animal-human outbreaks. “Compared to H5N1 and SARS, we’re getting on top of these diseases much, much faster.”
But he added that “people have become desensitized over time — it’s ‘Oh, O.K., another one.’ ”
And scientists say the world cannot afford to relax. The threat is real. New diseases are emerging faster than ever.
Peter Daszak, a parasitologist and president of the EcoHealth Alliance, has even put a number on it: 5.3 new ones each year, based on a study using data from 1940 to 2004. He and his co-authors blamed population growth, deforestation, antibiotic overuse,factory farming, live animal markets, bush meat hunting, jet travel and other factors.
Some aspects of the new viruses are scary. The Arabian coronavirus — now officially named MERS, for Middle East respiratory syndrome — has killed about half of those it infects, while SARS killed less than a quarter; in the lab, it replicates faster than SARS, penetrates lung cells more readily and inhibits the formation of proteins that warn the body that it is under attack.
In her closing remarks on Monday at the annual meeting of the world’s health ministers, Dr. Margaret Chan, director-general of the World Health Organization, said the virus was now her “greatest concern.”
Until experts figure out where it hides and how it infects humans, “we are empty-handed when it comes to prevention,” she said. “These are alarm bells, and we must respond.”
The H7N9 flu has been fatal in a quarter of known cases — the 1918 Spanish flu killed only 2 percent of its victims — and already has one dangerous mutation that helps it replicate at human body temperatures.
Still, better surveillance means that such threats are being caught sooner, giving time to develop countermeasures like vaccines and making it far less likely that a virus like the 1918 flu will ever again kill millions.
It also means that outbreaks that once might have faded away unnoticed now set off alarms, for better and for worse. Fifty years ago, even the dreaded H5N1 bird flu, which emerged in 2003 and kills about half its victims, might have been missed. It makes the jump to humans so rarely that even now it is basically a poultry problem: It has killed millions of chickens and occasional flocks of wild birds, but in a whole decade has claimed only 364 human lives, and that is known only because it can be distinguished from other flus by genetic typing.
The world’s ability to detect new diseases has sped up for reasons both technical and political.
First, rapid gene sequencing is now done in many laboratories.
Second, accurate symptom descriptions are instantly available. Web-based news services like ProMED, with scientist-members all over the world, issue several daily reports of outbreaks of everything from banana wilt to sheep bluetongue to human Ebola. Also, genetic sequences of new viruses are often posted on public databases, so their travels can be tracked. Scientists learned, for example, that a 2008 convention of Roman Catholic youth in Sydney, Australia, drew in influenza strains that then seeded new outbreaks all over the Northern Hemisphere.
Third, and very important, countries that used to hide their outbreaks now admit them. It would be virtually impossible now, for example, to repeat what happened in Africa in the 1980s, when presidents insisted for years that no one in their countries had AIDS.
The paragon of the new transparency cited most often is China. In 2003, it was excoriated for covering up its SARS outbreak. It later dismissed many of the officials involved. Now, with H7N9, “they’re being forthright and they’re also right at the forefront of research,” said Dr. W. Ian Lipkin, a microbe hunter at the Mailman School of Public Health at Columbia University, who just opened a partner laboratory at China’s Centers for Disease Control.
Saudi Arabia suffered a similar embarrassment in 2005, when it reacted slowly to poliospreading toward Mecca with pilgrims from northern Nigeria. Cases of paralysisultimately reached the hills outside Mecca and from there spread briefly as far as Indonesia. Saudi Arabia now gives polio vaccines to millions of pilgrims on arrival.
Covering up an outbreak is now a violation of World Health Organization regulations adopted in the wake of SARS. The rules require members to disclose any public health event that could spread beyond their borders.
Both H7N9 and MERS fit that description. Neither is easily transmissible, though both have almost undoubtedly infected family members, nurses or hospital roommates after long exposure. Most deaths from both have been in older patients with other health problems.
More worrisome is that no one knows how these viruses first infect victims.
H7N9 is avian, a mix of genes from domestic chickens and wild waterfowl. But many Chinese H7N9 patients have had no known bird contact, and the disease has been found only rarely in birds. Unlike H5N1, it does not wipe out flocks, so it is hard to hunt. Its spread pattern is roughly circular around Shanghai, suggesting it is mostly in poultry, not migratory birds. That could change if it starts traveling in wild ducks. (Rice farmers have duck farmers drive flocks into paddies to eat the snails that eat rice shoots, and wild ducks mix with them there.)
A decade ago, H5N1 also started in China but spread west in a zigzag pattern as wild waterfowl shared Mongolian lakes in summer with species that went southwest to Eastern Europe, Egypt and Africa and were caught in storms that blew them as far as Britain.
The origins of MERS are even more baffling. Scientists assume it is from bats, because it is genetically closer to coronaviruses found in them than to SARS or to the four known human coronaviruses, which cause common colds. But while bats in Mexico, Europe and Africa have similar viruses, none have yet been found in Arabian bats or in camels, goats or other animals that might transfer it to humans.
Dr. Daszak cited Nipah virus as an example of how humans get bat diseases. It was the inspiration for the 2011 movie “Contagion,” in which Gwyneth Paltrow had vivid death and autopsy scenes. Bat feces landed on fruit eaten by pigs, and Ms. Paltrow’s character was infected when she shook the unwashed hand of a casino chef who had just cleaned out a dead pig’s mouth. (In the first real-life Nipah outbreak, in Malaysia in 1999, most victims were pig farmers and butchers.)
But another study, done in Bangladesh by a colleague of Dr. Daszak, showed that humans get Nipah directly from bats by drinking fresh date palm sap. Sap-drinking bats crawled into the collecting jugs hung in trees, drooling and urinating in them.
Small numbers of sap drinkers may have died of Nipah for decades without it being noticed, Dr. Daszak said.
Right now, doctors are relying on isolating patients and antiviral treatment with oseltamivir and zanamivir for H7N9, and ribavirin and interferon for MERS.
If either virus goes epidemic, the next step would be vaccine.
The Centers for Disease Control and Prevention began making one against H7N9 in early April. The first of several candidates may be ready for manufacturers by the end of May, a spokeswoman said. How long it then would take to make and package millions of doses is unpredictable, she said, but should take at least six additional months.
Any vaccine for MERS will take much longer, said Mark A. Pallansch, director of the C.D.C.’s viral disease division. While flu vaccines have been produced around the world for 60 years, the passion for a coronavirus vaccine has faded since the SARS epidemic. Until recently, the most interested parties were poultry farmers, since one coronavirus kills turkeys.
Coronaviruses are unusually complex, so finding potential vaccine targets has been hard, and the extensive safety testing is expensive. Also, an animal model for testing was only recently found — macaque monkeys, in which the virus causes pneumonia.
A fungal spore, top, from an outer door frame and a bacterium from an inner door frame, sampled for The Wild of Our Home project. At each home those and seven other sites were swabbed: cutting board, kitchen counter, refrigerator, TV screen, door handle, toilet seat and pillowcase.
The New York Times, May 28, 2013, by Peter Andrey Smith, BOULDER, Colo. — On a sunny Wednesday, with a faint haze hanging over the Rockies, Noah Fierer eyed the field site from the back of his colleague’s Ford Explorer. Two blocks east of a strip mall in Longmont, one of the world’s last underexplored ecosystems had come into view: a sandstone-colored ranch house, code-named Q. A pair of dogs barked in the backyard.
Dr. Fierer, 39, a microbiologist at the University of Colorado Boulder and self-described “natural historian of cooties,” walked across the front lawn and into the house, joining a team of researchers inside. One swabbed surfaces with sterile cotton swabs. Others logged the findings from two humming air samplers: clothing fibers, dog hair, skin flakes, particulate matter and microbial life.
Ecologists like Dr. Fierer have begun peering into an intimate, overlooked world that barely existed 100,000 years ago: the great indoors. They want to know what lives in our homes with us and how we “colonize” spaces with other species — viruses, bacteria, microbes. Homes, they’ve found, contain identifiable ecological signatures of their human inhabitants. Even dogs exert a significant influence on the tiny life-forms living on our pillows and television screens. Once ecologists have more thoroughly identified indoor species, they hope to come up with strategies to scientifically manage homes, by eliminating harmful taxa and fostering species beneficial to our health.
But the first step is simply to take a census of what’s already living with us, said Dr. Fierer; only then can scientists start making sense of their effects. “We need to know what’s out there first. If you don’t know that, you’re wandering blind in the wilderness.”
Here’s an undeniable fact: We are an indoor species. We spend close to 90 percent of our lives in drywalled caves. Yet traditionally, ecologists ventured outdoors to observe nature’s biodiversity, in the Amazon jungles, the hot springs of Yellowstone or the subglacial lakes of Antarctica. (“When you train as an ecologist, you imagine yourself tromping around in the forest,” Dr. Fierer said. “You don’t imagine yourself swabbing a toilet seat.”)
But as humdrum as a home might first appear, it is a veritable wonderland. Ecology does not stop at the front door; a home to you is also home to an incredible array of wildlife.
Besides the charismatic fauna commonly observed in North American homes — dogs, cats, the occasional freshwater fish — ants and roaches, crickets and carpet bugs, mites and millions upon millions of microbes, including hundreds of multicellular species and thousands of unicellular species, also thrive in them. The “built environment” doubles as a complex ecosystem that evolves under the selective pressure of its inhabitants, their behavior and the building materials. As microbial ecologists swab DNA from our homes, they’re creating an atlas of life much as 19th-century naturalists like Alfred Russel Wallaceonce logged flora and fauna on the Malay Archipelago.
Take an average kitchen. In a study published in February in the journal Environmental Microbiology, Dr. Fierer’s lab examined 82 surfaces in four Boulder kitchens. Predictable patterns emerged. Bacterial species associated with human skin, like Staphylococcaceae or Corynebacteriaceae, predominated. Evidence of soil showed up on the floor, and species associated with raw produce (Enterobacteriaceae, for example) appeared on countertops. Microbes common in moist areas — including sphingomonads, some strains infamous for their ability to survive in the most toxic sites — splashed in a kind of jungle above the faucet.
A hot spot of unrivaled biodiversity was discovered on the stove exhaust vent, probably the result of forced air and settling. The counter and refrigerator, places seemingly as disparate as temperate and alpine grasslands, shared a similar assemblage of microbial species — probably less because of temperature and more a consequence of cleaning. Dr. Fierer’s lab also found a few potential pathogens, like Campylobacter, lurking on the cupboards. There was evidence of the bacterium on a microwave panel, too, presumably a microbial “fingerprint” left by a cook handling raw chicken.
If a kitchen represents a temperate forest, few of its plants would be poison ivy. Most of the inhabitants are relatively benign. In any event, eradicating them is neither possible nor desirable. Dr. Fierer wants to make visible this intrinsic, if unseen, aspect of everyday life. “For a lot of the general public, they don’t care what’s in soil,” he said. “People care more about what’s on their pillowcase.” (Spoiler alert: The microbes living on your pillowcase are not all that different from those living on your toilet seat. Both surfaces come in regular contact with exposed skin.)
Dr. Fierer has teamed up with Rob Dunn, a biologist at North Carolina State University, to sample the microbial wildlife in 1,400 homes across the United States. The project — known as The Wild Life of Our Home — relies on volunteers who swab pillowcases, cutting boards and doorjambs, then send samples in for analysis. (Full disclosure: I am a volunteer participant in the study, sending in swabs from my home.) Dr. Dunn hopes that the project will begin to unravel the consequences of moving from caves to creating environments around us in a haphazard way.
“For the entire history of humanity, we have created environments around us, in our daily lives, in a very unintentional way. The control that we’ve exerted is predominantly one in which we kill the ones that might be bad,” Dr. Dunn said. “That’s saved a lot of lives. It’s also favored this whole suite of species that we know very, very little about.”
So little is known of what’s in the home that a small sample can reveal something new. In their first study of 40 homes around Raleigh-Durham, N.C., published last week in the journal PLoS One, they found that humans rapidly “infect” the spaces in which they live. We leave bacteria by touching surfaces with our exposed skin, and at room temperature, a healthy human kicks up a “convective plume” of about 37 million bacteria per minute that disperse throughout the home and can survive for extended periods.
Species living outdoors find their way indoors, Dr. Fierer and Dr. Dunn found. Outdoor microbes are more frequent in homes with dogs, where fur-associated bacteria were found adhering to TV screens and pillowcases. “My expectation is that the effect of dogs on allergies is similar to the effect of getting your kid playing in the dirt,” Dr. Dunn said. “They end up being a surrogate for dirty nature in some ways, one dirty paw at a time.”
The data from the 1,400 homes are still being analyzed, but the team expects to learn how building materials, ventilation rates and cleaning habits affect the microbial map. “If you’re a vegetarian, do you have different microbes in your house than if you’re an omnivore?” Dr. Fierer said. “If you live in a forest, do you have different microbes than if you live in a desert? These are the types of questions that we don’t actually know the answer to. Yet.”
The effort to catalog the creatures of the great indoors began in earnest in 2004, whenPaula J. Olsiewski, a program director at the Alfred P. Sloan Foundation in New York, sent out a call to examine buildings as a first line of defense against bioterrorism. “If there’s a biological threat,” she said, “you’re probably looking for a needle in a haystack — but what’s the haystack? What’s going on in a building?” No one knows what the natural microbial life of a building should be.
The foundation has put up $28 million for projects to date, including continuing explorations into the microbial ecology of older two-story homes in the Northeast, train ticket kiosks in Boston, and the opening of a new hospital wing in Chicago. TheHospital Microbiome Project, led by Jack Gilbert of the University of Chicago, began sampling microbes in patients’ noses, armpits, hands and feces in February, along with those taking up residence in the newly constructed nursing stations and 10 patient rooms — a total of 12,000 swabs.
The yearlong investigation will tackle a pressing concern: One in every 20 patients acquires infections in a hospital, to the tune of an estimated 1.7 million infections and 60,000 deaths annually, according to the Centers for Disease Control and Prevention. Dr. Gilbert said, “The whole reason for doing this study is to stop people from dying.”
His preliminary findings suggest that the longer a patient stays in a given room, the more likely it is to acquire his or her unique microbial signature. The new hospital is being infected by its inhabitants. “You start to be colonized by bacteria from your mother in the amniotic sac,” Dr. Gilbert said. “If you use that as an analogue, we’re looking at the birth of a hospital.”
Another study, published in 2012 in The ISME Journal, found that hospital patients were more likely to encounter potential pathogens in mechanically ventilated roomsthan in ones with access to fresh air from outside. Jessica L. Green, the study’s author, a theoretical ecologist at the University of Oregon and director of its Biology and Built Environment Center, said she expected buildings to eventually be redesigned with a view toward managing their microbial impact on human health.
Architects and engineers also could try to cultivate benign or beneficial species, favoring certain conditions and altering our chronic, long-term exposure. One 2012 study in Finland, for example, found that plant diversity outside was linked to a greater variety of bacteria on human skin inside homes; moreover, teenagers with this increased biodiversity were at lower risk for allergies.
We are outliers among species, like leaf-cutter ants or termites, that garden beneficial organisms for their own benefit. “We keep beautiful forests far, far away. Crops that we can eat are far, far away,” Dr. Dunn said, adding that our cities are full of waste treatment plants. “An ant would never do that.”
The future of indoor ecology, now in its infancy, hinges on answering questions about what we should intentionally surround ourselves with. “Right now, we don’t understand how buildings work” as ecosystems, said Jordan Peccia, an environmental engineer at Yale.
Dr. Peccia is examining the link between increased fungal diversity indoors and reduced rates of asthma. Someday, he said, managing indoor biodiversity will run up against traditional concerns about building cost and energy efficiency.
“We’ve seen it as an improvement to make homes more insulated, but maybe that’s a mistake from the standpoint of ecological diversity,” he said. “We’re far from making a quantitative analysis of the trade-off. And once it’s shown, it’s another huge step to convince architects and engineers that this is important enough.”
We do not have a choice about whether to share our homes with microbes, then, but soon we may have an opportunity to open them up to better company.
Back in Colorado, Dr. Fierer talked with Amanda Phillips, 61, who lives at Home Q with her husband, Chester, 67, and their dogs Hunter and Chase. Ms. Phillips admitted she did some extra cleaning before the team’s arrival.
As she got up to leave, she said she was wary about the effort. “I don’t know if I really want to know what you’re finding,” she said. “But I’m excited to learn.”
Conversation with Microbiologist, Peter Smith
Innovation at Target Health – Target e*Studio™ Version 2 – EDC Made Simple, Released
Since 1999, Target e*CRF has been used in 25 unique regulatory approvals, including 3 approvals in 2012 (2 FDA; 1 EMA).
Target Health is pleased to announce the release of Target e*Studio™ Version 2. This elegant and innovative software allows CROs/Sponsors to build EDC applications with minimal programming expertise. Additional versions will be released over the next 6 months which should eliminate the need to perform any advanced programming. Of course, we are always there to help. Some of the current features include form and edit check builders, randomization module, drug/supply management, automatic generation of an annotated and blank eCRF, laboratory data upload, bookmarked pdf file of the final eCRF populated with the clinical trial data, eSignatures and integration with Target Encoder. Within the next few months we will be moving the development of applications (studies) to data management and many of our current staff assigned to software testing will be part of the team that will build EDC applications.
Target Health Inc., a full service eCRO, has been developing and using innovative web-based software tools for the paperless clinical trial. These software products provide CROs and Sponsors with a transparent environment and a significant productivity edge. Our business model includes partnering with other CROs in the utilization of our software.
What is our partnership model?
1. Minimal low cost initial investment which includes training
2. We can build or help you build the applications
3. Cost per study is based on study size
4. Hosting included
For more information about Target Health contact Warren Pearlson 212-681-2100 ext. 104). For additional information about software tools for paperless clinical trials, please also feel free to contact Dr. Jules T. Mitchel or Ms. Joyce Hays. The Target Health software tools are designed to partner with both CROs and Sponsors. Please visit the Target Health Website.
Israel BioMed – Partnering in Eastern Europe
Target Health has several partners doing clinical research in Eastern Europe. When we work together, all of our partners are committed to use our software products supporting the paperless clinical trial.
Our friends and colleagues Dr. Mihaly Juhasz, Managing Director and CEO of Accelsiors CRO and Consultancy Services Ltd, and Dr. Jeffrey Apter, President of Global Clinical Trials, LLC (GCT) will be at BioMed this year in Israel. Let us know if you would like to meet to see how we can be of assistance in Eastern Europe.
Accelsiors is a reliable and innovative Contract Research Organization, assisting and supporting its clients in pharmaceutical and biotechnology industry in achieving their goals in all phases of product development. Global Clinical Trials, LLC (GCT) is a full service Clinical Research Organization with headquarters in Princeton, NJ and additional offices in St. Petersburg and Moscow, Russia; Sofia, Bulgaria; Kiev, Ukraine; and Bucharest, Romania.
Common Food Supplement Fights Degenerative Brain Disorders
Pictures of the Many Uses of Soy
Widely available in pharmacies and health stores, phosphatidylserine is a natural food supplement produced from beef, oysters, and soy. Proven to improve cognition and slow memory loss, it’s a popular treatment for older people experiencing memory impairment. Now a team headed by Prof. Gil Ast and Dr. Ron Bochner of Tel Aviv University’s Department of Human Molecular Genetics has discovered that the same supplement improves the functioning of genes involved in degenerative 1) ___disorders, including Parkinson’s disease and Familial Dysautonomia (FD).
In FD, a rare genetic disorder that impacts the nervous system and appears almost exclusively in the Ashkenazi Jewish population, a genetic mutation prevents the brain from manufacturing healthy IKAP proteins — which likely have a hand in cell migration and aiding connections between nerves — leading to the early degeneration of 2) ___. When the supplement was applied to cells taken from FD patients, the gene function improved and an elevation in the level of IKAP protein was observed, reports Professor Ast. These results were replicated in a second experiment which involved administering the supplement orally to mouse populations with FD. The findings, which have been published in the journal Human Molecular Genetics, are very encouraging, says Prof. Ast. “That we see such an effect on the brain — the most important organ in relation to this disease — shows that the supplement can pass through the 3) ___-brain barrier even when administered orally, and accumulate in sufficient amounts in the brain.“
Slowing the death of nerve cells
Already approved for use as a supplement by the FDA, phosphatidylserine contains a molecule essential for transmitting signals between nerve cells in the brain. Prof. Ast and his fellow researchers decided to test whether the same chemical, which is naturally synthesized in the body and known to boost memory capability, could impact the genetic mutation which leads to FD.
Scientists applied a supplement derived from oysters, provided by the Israeli company Enzymotec, to cells collected from FD patients. Noticing a robust effect on the gene, including a jump in the production of healthy IKAP proteins, they then tested the same supplement on mouse models of FD, engineered with the same genetic mutation that causes the disease in 4) ___. The mice received the supplement orally, every two days for a period of three months. The authors then conducted extensive genetic testing to assess the results of the treatment. “We found a significant increase of the protein in all the tissues of the 5) ___,“ reports Prof. Ast, including an eight-fold increase in the liver and 1.5-fold increase in the brain. “While the food supplement does not manufacture new nerve cells, it probably delays the death of existing ones,“ he adds.
Therapeutic Potential for Parkinson’s
That the supplement is able to improve conditions in the brain, even when given orally, is a significant finding. Most medications enter the body through the blood 6) ___, but are incapable of breaking through the barrier between the blood and the brain. In addition, the authors noted the supplement’s positive effects extend beyond the production of IKAP. Not only did phosphatidylserine impact the gene associated with FD, but it also altered the level of a total of 2400 other genes — hundreds of which have been connected to Parkinson’s disease in previous studies. The authors believe that the supplement may have a beneficial impact on a number of degenerative diseases of the brain, including a major potential for the development of new medications which would help tens of millions of people worldwide suffering from these devastating 7) ___.
ANSWERS: 1) brain; 2) neurons; 3) blood; 4) humans; 5) body; 6) stream; 7) diseases
Soy from 7th Century BCE to Present
Engelbert Kaempfer (1651-1716)
Before 7th century BCE – The Shijing (Book of Odes) is China’s earliest classic and the world’s earliest document that mentions the soybean, which it calls shu. Zheng Xuan, the most important commentator of the 2nd century CE, confirms that shu refers to the soybean and that soybean leaves, called huo, can be pickled – presumably when green, then presumably eaten. In ancient China, the soybean was regarded as having many medicinal virtues, and was included as a preventive medicine in the second class of drugs. In the famous Materia Medica Pen Ts’ao Kang Mu, written by Li Shih-chen in 1597, the soybean is stated to be a specific remedy for the proper functioning of the heart, liver, kidneys, stomach, and bowels. It was also used as a specific remedy for constipation, as a stimulant for the lungs, for eradication of poison from the system, improving the complexion by cleaning the skin of impurities, and stimulating the growth and appearance of the hair. Fresh green soybeans and black soybeans were each ascribed a number of medicinal properties, and to this day black soybeans are widely used by Chinese doctors to strengthen the blood.
659 CE – The earliest known image of a soybean plant from the Xinxiu Bencao [Newly Improved Pharmacopoeia], by Su Jing
The oldest evidence of soy milk production is from China where a kitchen scene proving use of soy milk is incised on a stone slab dated around CE 25-220. It also appeared in a chapter called Four Taboos (Szu-Hui) in the book called Lunheng by Wang Chong (CE 82), possibly the first written record of soy milk. Evidence of soy milk is rare prior to the 20th century and widespread usage before then is unlikely. According to popular tradition in China, soy milk was developed by Liu An for medicinal purposes.
A.D. 100 – The term Sheng dadou [Chinese characters: raw/fresh + large + bean] appears in both Shennong bencao jing (Classical pharmacopoeia of Shen Nung) and later (about A.D. 450-500) in the Mingyi bielu (A critical record of famous doctors. A materia medica). However a careful analysis of the context by a Chinese scholar who is an expert in the history of Chinese foods and of soybeans indicates that this term refers to raw soybeans rather than fresh green soybeans. Therefore, surprisingly, we know of no early reference to green vegetable soybeans in China.
1275 – The word “edamame“ first appears in Japan when the well-known Buddhist Saint Nichiren Shonin writes a note thanking a parishioner for the edamame he left at the temple. In: Nichiren Shonin Gosho Zenshu (The Collected Writings of Saint Nichiren).
1406 – The Ming dynasty famine herbal titled Jihuang bencao, by Zhu Xiao is the earliest Chinese document seen that describes: (1) eating the tender leaves of soybean seedlings (doumiao); (2) eating the whole pods of young soybeans, (3) eating green vegetable soybeans; (4) or grinding the green beans for use with flour. The last three uses are recommended for times of famine only.
1620 – Maodou (Chinese characters: hairy + bean) are first mentioned in the Runan pushi [An account of the vegetable gardens at Runan], by Zhou Wenhua. “Maodou has green, hairy pods. It is also called qingdou (?green beans’). It is mentioned in the Bencao [materia medica] literature, which states that it has a sweet flavor, is neutral, and non-toxic. It can be used medicinally mainly to ?kill bad/evil chi.’ It stops bodily pain, eliminates water [reduces edema], dispels heat in the stomach, reduces bad blood, and is an antidote to poisonous drugs. Instructions are to “boil the beans in the pods until done, then remove the beans from the pods and eat them. The flavor will be sweet and fresh. Or you can remove the beans from the pods before cooking, and then cook the beans in lightly salted water. Or the beans can be placed on a metal screen over a charcoal fire to roast or dry them. They can be served with tea or fruits, as a snack.“ This is also the earliest document seen that gives medicinal uses for green vegetable soybeans.
1712 – Engelbert Kaempfer played a key role in introducing the soybean and soyfoods to the Western world.
1855 – T.V. Peticolas of Mount Carmel, Ohio, is the first American to mention green vegetable soybeans. In an article on soybeans in the Country Gentleman he wrote: “They are inconvenient to use green, being so difficult to hull.“
1856 – Only a year later, at least two Americans have apparently figured out how to shell them with ease, and to enjoy them. Thomas Maslin of Virginia wrote: “They are fine for table use, either green or dry.“ Abram Weaver of Bloomfield, Iowa, praises them in the Report of the Commissioner of Patents, Agriculture. “I had some of them cooked, while green, at their largest size, and found them delicious.“
1890 – The first large-seeded vegetable-type soybean variety arrives in America. Named Edamame, it was introduced from Japan by Charles C. Georgeson, who had been a professor of agriculture in Japan. Other early large-seeded varieties included Easycook (introduced in 1894 from Shandong Province, China) and Hahto (1915, from Wakamatsu, Japan).
1915 – William J. Morse (of USDA’s Office of Forage Crop Investigations), is the man most responsible for introducing green vegetable soybeans and vegetable type soybeans to the United States. Soy beans are mentioned for the first time in a USDA special publication titled “Soy beans in the cotton belt“ as “The green bean when three-fourths to full grown has been found to compare favorably with the butter or Lima bean.“
Engelbert Kaempfer (1651-1716) played a key role in introducing the soybean and soyfoods to the Western world. His book Amoenitatum Exoticarum, published in Germany in 1712, contained the first written description by a Westerner of the soybean plant and seeds (accompanied by the first Western illustration of these), plus the most detailed descriptions to date of the process for making miso and shoyu (Japanese-style soy sauce). Actually between 1597 and 1705 six Europeans had written of soyfoods (miso, tofu, and soy sauce (Dissemination to Europe), however none of these men knew how these soyfoods were produced, nor did they realize that they were made from soybeans. With the publication of Kaempfer’s influential and popular book in 1712 the Western world understood, for the first time, the connection between soybeans and soyfoods.
Kaempfer was born on 16 September 1651 at Lemgo, Germany, a small medieval town in the area of Westphalia, belonging to the Count of Lippe. Acquiring a very liberal education and preparing himself for the profession of Physick (physician), Kaempfer quickly showed himself to be naturally brilliant and inquisitive, with a remarkable capacity for learning foreign languages. He received his PhD in Poland, then traveled from there to Prussia, and then to Sweden. In 1689 he travelled to Batavia (today’s Jakarta, Indonesia). In May 1690 Kaempfer left Batavia for Japan in the capacity of medical officer or physician to the Embassy, which the Dutch East India Company sent once a year to the Japanese Emperor’s court. After stopping briefly in Siam, he arrived in Japan on 23 September 1690 at the island of Deshima (or Dejima) near Nagasaki in remote southwest Japan.
Amoenitatum Exoticarum. Kaempfer’s first major work, Amoenitatum Exoticarum, Politico-Physico-Medicarum (often rendered in English as Amoenitates Exoticae or Exotic Novelties), written in Latin, was published in Lemgo in 1712, some 16 years after his homecoming. The fifth fascicle of his 900-page work, which contained a description of the plants of Japan, included a full-page drawing by Kaempfer of a soybean plant, plus a description of the plant, and descriptions of how to make miso and shoyu (he called it sooju), both partially inaccurate. Kaempfer referred to the soybean as Daidsu or as mame, which is a general term for all types of beans. He later mentioned the black soybean under the names of Siuku (meaning uncertain) or Kuro Mame (“black beans,“ which he also referred to as Phaseolus Daidsu). He described it as a dwarf variety with medicinal properties; three or four, reduced to a powder, are administered in potions to asthmatics. Here is an exact translation from Latin of what Kaempfer wrote about soybeans and soyfoods: “Daidsu, as people and scientists call it, is also called “mame“ for its excellence. An upright bean, a leguminous plant like lupine, with whitish fruit somewhat larger than peas. A bean, similar to the aforementioned, but four feet high and with more branches and leaves, with upright stem, irregular branches and with hairs. It stretches forth leaves like the garden bean, but with more pubescence on the underside of the leaf. In the month of August it bears on pedicels in the axil of the leaves several bluish white flowers with a large standard, which resemble those of lentils. These tiny blossoms are followed by pods measuring 1.5 inches long, which are covered with heavy hairs (pubescence) resembling those of the yellow lupine. The pods contain two, and more rarely three seeds, similar to garden peas in size, shape and taste, but laterally somewhat compressed, and with a chestnut brown eye (hilum). This legume supplies to the Japanese kitchen vital elements, for they make from it the following:
1. A kind of pap that they call miso, which is added to dishes instead of butter. Butter is unknown under this strip of heaven.
2. And then the famous so-called shoyu, a sauce which is poured over if not all dishes, at least over all cooked and fried meals.
To produce miso, one takes one measure of mame or phaseolus daidsu which is cooked with water for a long time and then braved or ground and mixed into a soft pap. Under continued braying, common salt is added, in summer four parts, in winter three. If less salt is added, one gets the product quicker, but shelf life is shorter. After reducing has been repeated, one mixes the pap with koos or dehulled rice, and mixes the total by repeated braying. This rice in preparation has been boiled a little in the steam of unsalted water. One lets the mixture cool down and remain in a warm cellar one or two days and nights to ripen.
This mixture, which has the texture of a pap or spread, is put into a bowl that recently contained the popular sacki, a rice wine. Before using, one lets the bowl stand one or two months untouched.
Koos lends to the product an agreeable taste, and its production requires, like that of the Germans’ “polenta,“ the experienced hand of the master. Those therefore who make it are held in high esteem, and they sell it ready made.
To make shoyu one uses the same beans just as thoroughly cooked. And “muggi,“ which is barley or wheat fermented (with wheat the product becomes darker) which has been coarsely ground. One mixes equal units with ordinary salt, or only one unit with half of it. The beans are blended with the prepared grain, and one lets the mixture stand in a warm place under cover a day and a night for fermentation. Then the salt is added, one stirs the mass and mixes with water, normally two units to half. When this has been done, the well covered mass is stirred once (better two or three times) the next day and each subsequent day by means of an oven rake. This work is continued for two or three months, then the mass compressed and filtered and the liquid preserved in wooden containers. The older it becomes, the clearer and better it will be. The squeezed mass is again filled up with water and newly stirred and some days after treatment pressed again.“
It seems likely that Kaempfer learned of these processes from his servant-friend rather than witnessing them himself, or he may have also read of them in a book. It is interesting to note that he made no mention of tofu, Japan’s most widely used soyfood. But he did very clearly, for the first time, establish the connection between soybeans and soyfoods.
Only four years after the publication of his book, on 2 November 1716, Kaempfer died of the colic near his home town.
Kaempfer’s diaries, drawings (including his drawing of the soybean), and manuscripts are now carefully preserved among the rare materials of the British Museum in London. A copy of the first edition of his Amoenitatum Exoticarum and other person items are preserved in the Englebert Kaempfer Museum in Lemgo, Germany. Many of his botanical specimens are still preserved in the Natural History Museum, South Kensington, England.
Insights Gained From 20 Years of Soy Research
The following was published online in the Journal of Nutrition (2010 October 27) from the Department of Nutrition, School of Public Health, Loma Linda University, Loma Linda, CA 92350,
Soyfoods have long been recognized for their high-protein and low-saturated fat content, but over the past 20 years an impressive amount of soy-related research has evaluated the role of these foods in reducing chronic disease risk. Much of this research has been undertaken because the soybean is essentially a unique dietary source of isoflavones, a group of chemicals classified as phytoestrogens. The estrogen-like properties of isoflavones have also raised concern, however, that soyfoods might exert adverse effects in some individuals. There is intriguing animal and epidemiologic evidence indicating that modest amounts of soy consumed during childhood and/or adolescence reduces breast cancer risk. Evidence also suggests that soy reduces prostate cancer risk and inhibits prostate tumor metastasis, but additional clinical support for the chemopreventive effects of soyfoods is needed. Soy protein is modestly hypocholesterolemic and there is suggestive epidemiologic evidence that soyfoods lower risk of coronary heart disease (CHD) independent of effects on cholesterol. In clinical studies, soy favorably affects multiple CHD risk factors; however, with the exception of improved endothelial function, the data are too limited and/or inconsistent to allow definitive conclusions to be made. In regard to bone health, although recent clinical data have not supported the skeletal benefits of isoflavones, 2 large prospective epidemiologic studies found soy intake is associated with marked reductions in fracture risk. Soybean isoflavones also modestly alleviate hot flashes in menopausal women. Finally, other than allergic reactions, there is almost no credible evidence to suggest traditional soyfoods exert clinically relevant adverse effects in healthy individuals when consumed in amounts consistent with Asian intake.
NIH Fact Sheet – National Center for Complementary and Alternative Medicine (NCCAM)
This fact sheet from the National Center for Complementary and Alternative Medicine (NCCAM) provides basic information about soy-common names, what the science says, potential side effects and cautions, and resources for more information. The following information highlights some of what is known about soy when used by adults for health purposes.
Soy, a plant in the pea family, has been common in Asian diets for thousands of years. It is found in modern American diets as a food or food additive. Soybeans, the high-protein seeds of the soy plant, contain isoflavones – compounds similar to the female hormone estrogen. Traditional or folk uses of soy products include menopausal symptoms, osteoporosis, memory problems, high blood pressure, high cholesterol levels, breast cancer, and prostate cancer.
Soy is available in dietary supplements, in forms such as tablets and capsules. Soy supplements may contain isoflavones or soy protein or both. Soybeans can be cooked and eaten or used to make tofu, soy milk, and other foods. Also, soy is sometimes used as an additive in various processed foods, including baked goods, cheese, and pasta.
What the Science Says
Research suggests that daily intake of soy protein may slightly lower levels of LDL (“bad’) cholesterol and some studies suggest that soy isoflavone supplements may reduce hot flashes in women after menopause. However, the results have been inconsistent. There is also not enough scientific evidence to determine whether soy supplements are effective for any other health uses. However, NCCAM supports studies on soy, including its effects in cardiovascular disease and breast cancer, and on menopause-related symptoms and bone loss.
Side Effects and Cautions
Soy is considered safe for most people when used as a food or when taken for short periods as a dietary supplement. Minor stomach and bowel problems such as nausea, bloating, and constipation are possible. Allergic reactions such as breathing problems and rash can occur in rare cases. The safety of long-term use of soy isoflavones has not been established. Evidence is mixed on whether using isoflavone supplements over time can increase the risk of endometrial hyperplasia (a thickening of the lining of the uterus that can lead to cancer). Studies show no effect of dietary soy on risk for endometrial hyperplasia.
Soy’s possible role in breast cancer risk is uncertain. Until more is known about soy’s effect on estrogen levels, women who have or who are at increased risk of developing breast cancer or other hormone-sensitive conditions (such as ovarian or uterine cancer) should be particularly careful about using soy and should discuss it with their health care providers.