Do Your Homework Before the Big Interview

By John Rossheim, Monster Senior Contributing Writer 

 

Once upon a time, a job seeker landed an interview, skimmed the prospective employer's annual report, wowed the hiring manager with a few company facts and strolled into his dream job.
That late-'90s fairy tale rarely comes true these days. With employers in more control of the labor market, candidates feel compelled to give it their all in their interview preparation. And that includes mounting a broad, deep search for relevant information about the position, the company, the industry and even the interviewer.
Luckily for you, diverse resources, many of them free or cheap and available on the Internet, enable you to achieve that competitive edge if you're willing to put your nose to the grindstone -- or computer monitor.

Employers' Web Sites

Your prospective employer's corporate Web site is the best place to see the company as it wants to be seen. Do check out that annual report, but also look for a "press room" or "company news" page that links to recent news releases. As you mull all this information, consider how the open position, as detailed in the job posting, relates to the company's mission.
But don't stop there. Use the company site's search facility to query the names of the hiring manager and any others on your interview dance card. You may retrieve bio pages or press releases that give you insight into their most visible activities at the company. "Learning about the interviewer is probably the most valuable thing you can do," says Ron Fry, author of 101 Great Answers to the Toughest Interview Questions.

Research Employers

Next, get some vital statistics and independent perspectives on your prospective employer. Hoover's Online, for one, provides capsule descriptions, financial data and a list of competitors for thousands of large corporations.
Your 401k or mutual fund account with a major broker likely provides more detailed research on publicly traded companies and industries, free of charge. "You may be able to go to competitors for the prospective employer's financials," says Joyce Lain Kennedy, Los Angeles Times career columnist and author of Job Interviews for Dummies.

News Sources

Now broaden your perspective and see what general-interest and business publications and Web sites are writing about the employer and its industry. You can find a wide range of media outlets at NewsLink, notes Kennedy. Search national publications for news on major corporations; use hometown newspapers to learn about small businesses and how big businesses interact with their local communities. Refdesk and bizjournals.com also offer gateways to journalism on companies and industries.

Trade Journals

Taking cues from your research so far, drill down into your target company and its place in the industry by looking at trade journals and other specialized publications. "Get a few months of the relevant trade journal," advises Fry. "You're going to find out about new products and what the trade is saying about the company."
You may find hard copies of trade journals at university or public libraries. Some journals are available for free or by subscription through their own Web sites; the full text of thousands more is available through periodical databases like ProQuest and InfoTrac. You may even be able to access InfoTrac for free via the Web, using just the membership number on your public library card. Contact your local library for details.

Industry Directories

By now, you've probably got some very specific questions regarding the employer and your potential role there. Go directly to the grapevine by making contact with other workers at your target company or elsewhere in the industry. "If you belong to a professional organization, go to its directory," says Marilyn Pincus, author of Interview Strategies that Lead to Job Offers. If you don't belong, consider joining; check out the American Society of Association Executives' Gateway to Associations Directory.
Of course, you can also use networking services to get in touch with people inside the company.

Google

Finally, if you hope to have a company ogling you, try Googling them first. You just might come up with a nugget you would have missed otherwise.
While you're at it, Google yourself to make sure you and the interviewer are on the same page. Because if he's savvy, he's doing unto you as you've just done unto him and his company.

 Very nice note published to David Vaught's LinkedIn page today we wanted to share with our clients and candidates: 

The Thank You Letter: A Lost Art

Once upon a time, the primary form of communication was the written letter. People took pride in using correct grammar and spelling. It is becoming a lost art (my writing here is probably full of errors thus proving my point). However, the thank you letter is a very important part of the interview and hiring process. It reveals many things about the candidate. The absence of one is usually the end of the road for that candidate. So, in the electronic age, how do we successfully pen a great letter.
Here are some basics. First have electronic personal stationary. Anyone that can surf Facebook has the skills to do it. Write your letter as if they will print it off and place it in a file. Start with the person's company and address. Name and title. Finally the date. You would be shocked at the number of letters I see that are not set up that way. Begin your letter that should be three paragraphs. A paragraph is defined as a minimum of two sentences.
Start off with thanking them for their time etc. The second paragraph is the meat of the letter. You may want to highlight one great thing you have done to solidify that in their mind. This might be a great time to handle that one objection they had about you on the interview. Finally, the final paragraph tells them you want the opportunity and you look forward to moving forward in the process.
Attach the letter to an e-mail.....not in the body of an e-mail.
Just my abbreviated thoughts on the thank you letter. See, it pays to go to English class in school!!

The month of May marks the Bales Company’s 37th Anniversary!
We take pride in having contributed many of the talented people who have fueled the technological innovation, sales growth, market penetration, and financial success in Medical Products, Devices, and Capital Equipment. We have had great success in putting together the first teams for successful Start Up and Early Emerging companies in the industry, and would like to like to extend our gratitude to all of our clients who have made another anniversary possible!

Kind Regards,
Sally Bales
President CEO
The Bales Company
904.398.9080 ext.208
sbales@balescompany.com
www.balescompany.com

Measles Virus as a Cancer Fighter - Mayo Clinic

Published on May 14, 2014

A medical first -- a woman with an incurable form of cancer has had all signs of living cancer cells eradicated from her body for at least 6 months. What's more, it was accomplished in a single treatment. And the magic potion -- was the measles virus.

Parkinson's Disease and Individualized Medicine

Parkinson's Disease and Individualized Medicine

Wonderful article from the Mayo Clinics Online Research Magazine 

 High-tech advances in individualized medicine are helping Mayo Clinic researchers discover genomic causes of Parkinson's disease faster than ever.

Until recently, Parkinson's disease was thought to arise from exposure to environmental triggers, such as carbon monoxide or pesticides, and in some cases, that's true. But Zbigniew K. Wszolek, M.D., a neurologist at Mayo Clinic in Florida, always thought there was something more at play.
In the 1980s, he began collecting blood samples from patients and volunteers, compiling family histories, and building up connections to hunt down the genes behind Parkinson's disease. It took him a decade to find the first gene.
Since then, more than a dozen genes have been discovered that play a role in Parkinson's disease, half of them by Dr. Wszolek and his colleagues at Mayo Clinic in Florida. In fact, scientists now believe that Parkinson's disease is primarily caused by genetic factors, with only a small percentage of cases stemming from environmental exposures.
Mayo Clinic researchers are using this newfound knowledge and the latest genomic technologies to further pinpoint more of the genes at fault and to illuminate the true causes of Parkinson's disease.

Early researchers seek environmental clues

Though it isn't clear when Parkinson's disease was first recognized, a number of ancient medical texts describe possible treatments for the disease's characteristic muscle rigidity, tremors and slowness of movement. Today, Parkinson's disease is the second most common neurodegenerative disorder in the United States, affecting about half a million Americans, according to the National Institutes of Health.
Although Parkinson's is a relatively common disease, there doesn't seem to be one common cause. Early research focused on possible connections between Parkinson's and environmental factors.
For example, many of the people who survived the 1918 Spanish flu pandemic went on to develop a virally induced form of Parkinson's known as postencephalitic parkinsonism. In the 1980s, people who had taken heroin contaminated with the neurotoxin MPTP developed a permanent form of parkinsonism that closely resembles Parkinson's disease.
Because of cases like these, researchers began looking for other environmental toxins that could trigger Parkinson's and found that people exposed to certain pesticides were at an increased risk, while tobacco smokers were at a reduced risk. By the time Dr. Wszolek was doing his residency, the Parkinson's disease research community was largely focused on uncovering more potential environmental factors.

A shift in focus

But then Dr. Wszolek's discovery led him down a different path.
"I came across a patient whose sister, mother and grandmother all had symptoms of Parkinson's disease," Dr. Wszolek recalls. "I asked myself, 'How could this person have such a strong family history if environmental factors were the sole cause? Perhaps the environment was playing a role, but couldn’t genetics be playing one as well?' "
Answering that question wasn't as easy as it may seem.
Dr. Wszolek traveled around the country, personally meeting with and examining his patient's family members to confirm their diagnoses. He eventually expanded the patient's family tree to more than 300 members and traced its origin back to colonial Virginia. Dr. Wszolek undertook similar endeavors with a number of other families affected by Parkinson's disease.
In part because of these efforts, he and his fellow researchers have identified a laundry list of genes — tau, alpha-synuclein, LRRK2, dynactin-1, VPS35, EIF4G1 and CSF1R — that can cause neurodegenerative disease. Dr. Wszolek and his colleagues have attempted to figure out how mutations in these genes set off the manifestations of Parkinson's disease.
Among these scientists is Owen A. Ross, Ph.D., a molecular biologist at Mayo Clinic in Florida. Dr. Ross' mentor, former Mayo Clinic neuroscientist Matt Farrer, Ph.D., had found that patients with one extra copy of the alpha-synuclein gene develop familial Parkinson's disease in their 50s while those with two extra copies — double the normal amount — develop the disease in their 30s. Dr. Ross then found that common variation in the alpha-synuclein gene could increase the risk of disease in patients with no family history — these were categorized as sporadic cases.
From a scientific standpoint, it made sense that if twice as much protein causes a severe form of Parkinson's and a 50 percent increase results in a moderate form of the disease, then perhaps a 10 to 20 percent increase would increase the risk of sporadic disease. These findings helped overturn the previously held belief that genes found in the rare cases of disease running in families weren't relevant to the more-frequent sporadic patients.

Conflicting theories about Parkinson's

Fluorescence in situ hybridization (FISH) showing alpha-synuclein (SNCA) triplication. At top, three copies of SNCA gene on one chromosome, and below, two copies of SNCA gene on one chromosome.

But Dr. Ross says that despite all that researchers have learned about the Parkinson's disease, there are still competing theories about why it occurs.
For instance, researchers have discovered that small clumps of protein molecules called Lewy bodies accumulate in the brains of people with Parkinson's disease. Researchers can't seem to agree about whether these clumps are protective or toxic. Some think the clumps act like a garbage bin, keeping all the protein aggregates in one place so that the rest of the brain cells can stay clean and function. Others think the presence of the aggregates themselves is toxic to the brain, eventually killing the cells that contain them. Still others think it is a combination of the two scenarios.
With researchers disagreeing on that fundamental point, deciding the true mechanism behind Parkinson's disease becomes even more complicated. But according to Dr. Ross, it is probably supposed to be that way.
"I think it may well end up being that many roads lead to Damascus. That there is a final endpoint, but that there are many different ways to get there," Dr. Ross explains. "You could pick any pathway that will lead to cell death — impaired protein degradation, mitochondrial dysfunction, increased inflammation — and say it's a potential cause of Parkinson's disease. Therefore, we need to start thinking about Parkinson's disease as a single set of symptoms with many different causes, and realize that there may be no single treatment or cure for everyone."

The rise of individualized medicine

Lewy body, the protein formation in a nerve cell in Parkinson's, also causes a form of dementia.

At Mayo Clinic, the idea of tailoring health care to fit each patient's unique medical condition is not new. Since its inception, Mayo Clinic has strived to provide personalized care to every one of its patients. But with the completion of the Human Genome Project and the technological advances that have followed, the potential for these tailored treatments has greatly expanded.
So Mayo Clinic created the Center for Individualized Medicine (CIM) to bring together physicians and scientists to explore how to use the latest genomic and molecular technologies to guide clinical practice. Alexander S. Parker, Ph.D., associate director of the Center for Individualized Medicine, and a neurology researcher at Mayo Clinic in Florida, says the center continues Mayo Clinic's tradition of research to help individual patients, but at a rapidly accelerated pace.
For example, a primary goal is to provide vital funding to Mayo Clinic investigators who are conducting research that could inform the next generation of personalized care.
The center recently awarded Drs. Wszolek and Ross and neurogeneticist Rosa Rademakers, Ph.D., of Mayo Clinic in Florida, a combined $50,000 grant to push their findings in Parkinson's disease toward the clinic. The researchers are creating laboratory models of the very same gene mutations that they discovered in patients and using them to test different chemicals, any one of which could eventually be found effective in treating Parkinson's disease and developed into a new medication.
"We try to make every investigator who gets CIM funding realize that we will fail if their work doesn't eventually end up in the clinic making a difference for a patient," Dr. Parker says. "That is different for a lot of investigators who are used to focusing on getting papers published or keeping their lab funded. Publications and grant funding are great, but the goal here is to change the way physicians practice medicine."
The Center for Individualized Medicine may be setting the bar high, but it is also building the resources and infrastructure necessary for researchers to take those next crucial steps. On the Florida campus, the center plans to increase bioinformatics expertise to analyze the vast amounts of data being generated, enhance biospecimen collection capabilities, and establish a biobank of samples from research participants without Parkinson's disease. The center also plans to open an individualized medicine clinic at Mayo Clinic's Minnesota and Arizona campuses.

Future challenges

These initiatives are helping investigators make new discoveries that are having a significant impact on a variety of human diseases, including other neurodegenerative disorders besides Parkinson's.
Last year, for example, Dr. Rademakers — supported by the Center for Individualized Medicine — uncovered a completely new genetic cause for amyotrophic lateral sclerosis (ALS) and also found that another gene associated with parkinsonism is a major risk factor for ALS. Likewise, Dr. Ross showed that a gene related to ALS may contain mutations that increase the risk of Parkinson's disease.
"Those studies have been an eye-opener, because suddenly we are seeing genes discovered in other neurodegenerative disorders that we didn't think had anything to do with Parkinson's disease, actually coming back and being risk factors for the disease," explains Dr. Ross, who collaborates with Dr. Rademakers.
Even when those risk factors are added to the dozen or so genes that have been identified at Mayo Clinic and elsewhere, they still only account for a small fraction — perhaps less than 5 percent — of the causes of Parkinson's disease. Dr. Ross thinks that ultimately as much as 90 percent of the disease risk may be attributed to genetics, with the rest related to environmental and other factors.
Although there is clearly a long way to go, Dr. Ross and his colleagues say that the latest genomic technologies, and the Center for Individualized Medicine support, are already making it possible to discover new genes faster than ever before.
Consider Dr. Wszolek. When he started his search in 1987, he had to collect blood specimens from about 25 affected people and hundreds of family members before he could start looking for the causative gene. Even after laying all that groundwork, Dr. Wszolek says he still had a hard time finding it.
For his latest discovery, he pinpointed a new gene using only three patients and 30 family members.
"The last 10 years saw enormous progress in the development of genetic technologies and that counts for a lot," Dr. Wszolek says. "It takes less effort, which is good because I want to spend my time finding more genes. My hope is for us to find these genes, understand them better, and then translate those findings in a way that gives families hope that we will be able to come up with treatments that work for them."

Reducing Radiation Exposure One Image at a Time

Wonderful article  Published by the Mayo Clinic's Online Research Magazine, Discovery's Edge

  Reducing radiation exposure from computerized tomography (CT) scans has become one of the primary goals of Mayo Clinic's CT Clinical Innovation Center. At a time when CT scans are being used with greater frequency, the work of Cynthia H. McCollough, Ph.D., and her research colleagues has cut the risk of exposure without sacrificing image quality or diagnostic capability.

Cynthia H. McCollough, Ph.D., and Lifeng Yu, Ph.D.

X-rays have been a medical tool for more than a century. The exquisite details of CT scans have offered unique views of the inside of the body for more than a generation. They're vital in helping doctors diagnose a wide range of conditions, plan treatment, monitor progress and guide procedures.

However, recent reports in scientific literature and the public media have raised questions about the use of CT scans because they increase a patient's exposure to radiation, which, in high doses, is associated with an increase in cancer risk.

Although the average amount of radiation exposure from a single CT scan is a fraction of the radiation a person receives from nature in a year, Mayo Clinic has been committed to reducing unnecessary exposure and minimizing the risks without sacrificing the image quality.

"At high doses of radiation — much higher than the levels used in a medical imaging exam — the data clearly demonstrate an increased risk of cancer," says Cynthia H. McCollough, Ph.D., a medical physicist at Mayo Clinic in Rochester, Minn., who directs the CT Clinical Innovation Center and who is an internationally recognized expert on radiation exposure and risk.

"Medical imaging operates well below those levels," she says. "It's analogous to taking an aspirin. Taking a whole bottle all at once is risky, but taking two pills isn't. Still, if only one pill will get rid of my headache, I'll use just one. The radiation exposure from a CT scan isn't dangerous, but if we can use an even lower amount, without compromising the exam, that's what we'll do."

Benefits outweigh the risks

In addition to educating patients and physicians about the low risks of a CT exam, Dr. McCollough and the CT Clinical Innovation Center focus on maximizing the benefit-to-risk ratio.

She is continually looking for ways to reduce radiation exposure while maintaining the needed image quality. A crucial step in that process includes better defining what level of image quality is needed.

"We don't always need pretty pictures," Dr. McCollough says. "We only need pictures that clearly show the disease or injury. For some conditions, a really low exposure of radiation can be used."

Some people still worry, however, that a number of small doses will add up so much that the medical benefits no longer outweigh the cancer risk.

Dr. McCollough emphasizes that this is not the case, even for patients who receive several imaging exams throughout the course of their lives, or even over the course of one illness or injury.

"We know that the body can repair damage to cells from radiation," she says. "Our bodies do this all the time, since there is naturally occurring radiation all around us. In radiation therapy, for example, the treatment dose is delivered over many days so that the healthy tissue has time to repair itself between treatments. The risk from a small dose of radiation is always low, even if a patient has had many past exams."

Bridge between research and clinic

The Somatom scanner at Mayo Clinic.

A comparison of images of a patient's CT scan from one year to the next shows a 60 percent reduction in radiation used for the same single image.

One way Mayo Clinic has worked to reduce radiation exposure has been to create a bridge between the scientists who do the research and the doctors who deliver patient care. The CT Clinical Innovation Center is a hybrid of basic research and clinical care.

"We're located right in the middle of a clinical practice," Dr. McCollough says. "So in the morning, if a technologist is scanning a patient and they're not sure about something or see something interesting, they literally just open a door and there are five medical physicists around to talk to. We've created a bridge between the nerdy scientists and the actual delivery of care."

To reduce the amount of radiation patients are exposed to, the CT Clinical Innovation Center takes several routes.

"The most basic, low-tech thing we can do is to 'right-size' the dose," Dr. McCollough says.

Mayo Clinic has developed a computerized set of electronic protocols, or standards. If an adjustment is made to a protocol, the correct, new information is instantly available at all 25 CT scanners on the Mayo Clinic campus in Rochester, Minn., as well as at the Mayo campuses in Florida and Arizona, and all Mayo Clinic Health System sites.

A protocol review team ensures that the scanning instructions are kept up to date. And much like the automatic exposure feature on a camera, CT scanners can now automatically adjust the radiation exposure that a patient receives based on the type of exam and the size of the patient.

Mayo Clinic has had a business collaboration with Siemens Healthcare, one of the major CT scanner manufacturers, to develop and refine this technology during the past decade.

One of Dr. McCollough's medical physicist colleagues at Mayo Clinic in Rochester, Lifeng Yu, Ph.D., developed an algorithm that automatically selects the best X-ray energy for a given exam and patient. This is different from just adjusting the exposure level.

"X-rays come in different energies, and it is more dose efficient to use lower energies in children and smaller patients," Dr. McCollough says. "In the smallest patients, it drops the dose 40 to 50 percent."

Siemens Healthcare also pioneered a new scanner technology called the Somatom Flash. This new technology generates high-quality images of the lungs without requiring patients to hold their breath.

Mayo Clinic physicists, led by Dr. Yu, also tested the new scanner with a brain perfusion imaging protocol that cuts radiation dose by nearly 50 percent. They simulated scans at continually lower dose levels using patient data. Neuroradiologists evaluated the images, determining the lowest dose needed to deliver the best image quality.

"Everything we're doing with dose reduction is to make sure patients get the exams they need at the lowest radiation doses," Dr. McCollough says.

Reducing radiation dose in the cath lab

A specific specialty where use of medical radiation has increased dramatically is in cardiology. Charanjit S. Rihal, M.D., a cardiologist at Mayo Clinic in Rochester, Minn., recently published the results of a quality-improvement project in the area of catheterization.

"The improvement consisted of three very simple but very effective things," Dr. Rihal says. First, technologists adjusted the number of pulses of X-ray per second that the CT scanner delivers, also called the frame rate. They cut the frame rate from 30 pulses per second to 7.5 pulses per second. Second, they turned down the actual dose of radiation that the machine emits. Finally, they developed a culture of radiation safety.

"We launched educational programs for our trainees and staff on the basics of radiation physics and radiation safety," Dr. Rihal says. Trainees also now have to pass an exam about radiation safety.

As part of the culture of safety, the amount of radiation that a patient has received is now reported right on the official catheterization report, further encouraging staff to use as little radiation as possible.

The results of the changes have been encouraging.

"We reduced the amount of radiation by at least 40 percent, and in some cases by as much as 70 percent," Dr. Rihal says. He adds that if technologists need a higher dose of radiation to gain more image clarity, "It's easy just to twist the dials on the machine and crank it up for a few seconds. There's no need to routinely use the higher dose."

Working with referring physicians

 Charanjit S. Rihal, M.D., is chair of cardiovascular diseases at Mayo Clinic.

 

Adjusted CT scans dramatically limit radiation exposure without affecting diagnostic resolution.

The CT Clinical Innovation Center partners with Mayo Clinic physicians to lower the radiation dose for various forms of CT scans.

For example, working with uroradiologist Akira Kawashima, M.D., Ph.D., at Mayo Clinic in Rochester, scientists from the center developed a low-dose protocol for people who have experienced pain with prior kidney stones.

A CT scan is the standard method to diagnose kidney stones, but people who have recurrent stones may be concerned about the radiation from multiple scans. Drs. McCollough and Kawashima worked together to turn down the dose while making sure the image quality is high enough to catch any potential stone.

"It worked so well that we realized we weren't missing any stones, so that is the new protocol," Dr. McCollough says.

In another example, Joel G. Fletcher, M.D., a radiologist and the medical director of the Mayo Clinic CT Clinical Innovation Center in Minnesota, worked with pediatric oncologists to lower the radiation dose for follow-up CT scans for children diagnosed with cancer who had completed treatment.

"We just kept turning down the dose until finally it was down to the lowest setting the scanner would run at," Dr. McCollough says. With each setting, a pediatric radiologist would look at the scan to ensure that the image was still clear. "We try to do the limbo: You know, 'How low can you go?' "

With education, new technology and collaboration among physicists, radiologists and other physicians, Mayo Clinic is answering that question.

REGENERATING HEART TISSUE THROUGH STEM CELL THERAPY

This was a great article from the Mayo Clinics online research magazine:

Summary

A groundbreaking study on repairing damaged heart tissue through stem cell therapy has given patients hope that they may again live active lives. An international team of Mayo Clinic researchers and collaborators has done it by discovering a way to regenerate heart tissue.

Andre Terzic, M.D., Ph.D., is the Michael S. and Mary Sue Shannon Family Director, Center for Regenerative Medicine, and the Marriott Family Professor of Cardiovascular Diseases Research at Mayo Clinic in Minnesota.

Miroslav Dlacic's heart attack changed his life drastically — and seemingly forever. His damaged heart made him too tired to work in his garden or to spend much time at his leather-accessories workshop in Belgrade, Serbia. Like many patients with heart problems, Dlacic, who is 71, thought he would live his remaining years in a weakened condition.

Then, a groundbreaking Mayo Clinic trial of stem cell therapy to repair damaged heart tissue changed his life again — this time for the better.

Dlacic agreed to participate in the Mayo Clinic stem cell trial through the hospital in Serbia where he is treated. Two years later, Dlacic is able to walk again without becoming worn out.

"I am more active, more peppy," he says. "I feel quite well."

"It's a paradigm shift," says Andre Terzic, M.D., Ph.D., director of Mayo Clinic's Center for Regenerative Medicine and senior investigator of the stem cell trial. "We are moving from traditional medicine, which addresses the symptoms of disease, to being legitimately able to cure disease."

For decades, treating patients with cardiac disease has typically involved managing heart damage with medication. It's a bit like driving a car without fixing a sluggish engine — you manage the consequences as best you can and learn to live with them.

But in collaboration with European researchers, Mayo Clinic researchers have discovered a novel way to repair a damaged heart — to actually fix the machine.

In Mayo Clinic's breakthrough process, stem cells are harvested from a patient's bone marrow. The stem cells undergo a laboratory treatment that guides them into becoming cardiac cells. The treated cells are then injected into the patient's heart in an effort to grow healthy heart tissue.

The study is the first successful demonstration in people of the feasibility and safety of transforming adult stem cells into cardiac cells, Dr. Terzic says.

This discovery could have implications for millions of people. Cardiovascular disease is the leading cause of death worldwide, according to the World Health Organization. In the U.S. alone, about 5.8 million people have heart failure, and the number is growing, according to the National Institutes of Health.

Beyond heart failure, the Mayo Clinic research also is a milestone in the emerging field of regenerative medicine, which seeks to go beyond palliative treatment to fully heal damaged tissue and organs.

 Creating a heart repair kit

This image shows the process used in the clinical trials to repair damaged hearts. Cardioprogenitor cells is another term for cardiopoietic cells, those that were transformed into cardiac cells.

Transformation: The cardiopoietic cells on the left react to the cardiac environment, cluster together with like cells and form tissue.

Stem cell transplants traditionally have been used successfully to treat diseases such as leukemia and lymphoma. Translating that success to heart disease is a huge challenge.

"In leukemia and lymphoma, the transplanted bone marrow is repairing bone marrow," Dr. Terzic says. "Here, we are asking something unique of the stem cells — to repair another organ. It's an anatomical mismatch."

But Mayo Clinic researchers continued their research, inspired by an intriguing discovery.

In the early 2000s, they analyzed stem cells from 11 patients undergoing heart bypass surgery. The stem cells from two of the patients had an unusually high expression of certain transcription factors — the proteins that control the flow of genetic information between cells. Clinically, the two patients appeared no different from the others, yet their stem cells seemed to show unique capacity for heart repair.

"That gave us the idea to convert nonreparative stem cells to become reparative," Dr. Terzic says.

Doing so required determining precisely how the human heart naturally develops, at a subcellular level. That painstaking work was led by Atta Behfar, M.D., Ph.D., a cardiovascular researcher at Mayo Clinic in Rochester, Minn.

With other members of the Terzic research team, Dr. Behfar identified hundreds of proteins involved in the process of heart development (cardiogenesis). The researchers then set out to identify which of these proteins are essential in driving a stem cell to become a cardiac cell.

Using computer models, they simulated the effects of eliminating proteins one by one from the process of heart development. That method yielded about 25 proteins. The team then pared that number down to 8 proteins that their data indicated were essential.

The research team was then able to develop the lab procedure that guides stem cells to become heart cells. The treated stem cells were dubbed cardiopoietic, or heart creative.

A proof of principle study about guided cardiopoiesis, whose results were published in the Journal of the American College of Cardiology in 2010, demonstrated that animal models with heart disease that had been injected with caridiopoietic cells had improved heart function compared with animals injected with untreated stem cells.

Hailed as "landmark work," by the journal's editorial writer, the study showed it was indeed possible to teach stem cells to become cardiac cells.

From the lab to European clinical trials

Atta Behfar, M.D., Ph.D., is the lead author of Mayo Clinic's regenerative heart study.

In regenerative medicine, the step between lab tests and clinical trials is a big one.

For one thing, the amount of stem cells must be greatly expanded. The researchers also need to find a partner with expertise in managing the increased production of stem cells and the logistics of clinical trials.

Enter Cardio3 Biosciences, a bioscience company in Mont-Saint-Guibert, Belgium. Dr. Behfar spent several months in Belgium working with Cardio3.

"The interaction with Cardio3 was crucial to driving Mayo Clinic's technology forward," he says.

Why European trials first? It's faster to get many clinical studies approved in Europe compared with the United States. Trials will be held in the U.S. eventually, but Dr. Terzic had many previous collaborators at European medical centers ready to collaborate. And Cardio3 had a long history of coordinating trials in multiple countries.

The clinical trials involved 45 patients in Belgium, Switzerland and Serbia. All of the patients, including Miroslav Dlacic, experienced heart failure as a result of heart attacks.

The patients were randomly assigned to a group that received cardiopoietic cells or to a control group that received standard care for heart failure. This was a safety and feasiblity trial, which will lead to much larger, multiple-site trials.

The results were significant. Stem cells from each patient in the cardiopoiesis group were successfully guided to become cardiac cells. The treated cells were injected into the heart wall of each of those patients without apparent complications.

"It's critical that this new process of cardiopoiesis was achieved in 100 percent of cases, with a very good safety profile," Dr. Terzic says. "We have demonstrated the feasibility and safety of this procedure."

Although this initial clinical trial wasn't designed to assess the procedure's effectiveness, the indications were positive, researchers said.

Typically, failing hearts pump less blood and become enlarged. Six months after stem cell therapy, every patient in the cardiopoiesis group had increased blood flow from the heart to the rest of the body. And each patient showed decreased heart volume, all indicators of improved heart health.

The patients also were able to walk longer distances than they could before treatment — on average. By comparison, the 10 patients in the control group showed no change or even deterioration in these measures.

"This preliminary study was not designed to be definitive. But already at six months, there was a significant benefit for patients," Dr. Terzic says.

He notes that anecdotal evidence of improvement over the study's two-year follow-up period came from a patient who was unable to summon sufficient breath to play his trumpet before the experimental treatment but now can do so, and from another who has resumed riding a bicycle.

"We are enabling the heart to regain its initial structure and function," Dr. Terzic says, "and we will not stop here."

The clinical trial findings are expected to be published in the Journal of the American College of Cardiology in 2013.

Meanwhile, research to improve the injection process and cell effectiveness is underway.

"We are working on novel delivery tools that dramatically increase the cardiopoiresis cells retained by the heart," Dr. Behfar says. "We have technology and know-how about these stem cells that we couldn't even have dreamed of 10 years ago when this work began."

Multicenter, phase III clinical trials are being planned for larger groups in Europe, to be followed by trials in the U.S. Much more information is needed before this technique can be validated and approved for regular clinical use, though.

Other regenerative efforts

Mayo Clinic is uniquely positioned to pursue this complex therapy. In addition to its global reach, its Center for Regenerative Medicine is at the forefront of efforts to develop reparative solutions for a range of conditions besides heart disease.

"With the cardiopoiesis research, we have shown that regenerative medicine can really work," Dr. Terzic says. "We are now actively working on regenerative medicine in the areas of diabetes, liver and lung disease, neurologic disorders, and orthopedic surgery."

The interdisciplinary collaboration that provides the foundation for the Center for Regenerative Medicine epitomizes Mayo Clinic's approach to research and treatment. So, too, does a commitment to using talent and technology to enhance patient care.

"The Mayo history of being an unbelievable medical and scientific center is the reason I am here," Dr. Terzic says. "We have extremely creative people here as well as the environment that allows them to develop definitive solutions to problems."

The research was supported by the National Institutes of Health; the Marriott Heart Disease Research Program; the Mayo Clinic Center for Regenerative Medicine; the Ministry of Education and Science of Serbia; Cardio3 BioSciences; the Walloon Region General Directorate for Economy, Employment and Research; and the Meijer Lavino Foundation for Cardiac Research, Aalst, Belgium. Dr. Behfar received travel support from Cardio3 BioSciences. He and Dr. Terzic received Mayo Clinic administered research grants from the National Institutes of Health and Cardio3 BioSciences. Mayo Clinic has rights to future royalties from Cardio3 Biosciences.

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