February 17-23, 2008 is National Engineers Week, or E-week. This is a week in which people all over the nation hold events to strengthen the community’s understanding and awareness of engineering. It is also designed to encourage students to pursue careers in engineering and related technological fields to help advance the country.

E-week is celebrated everywhere and locations can be found at the National Engineers Week website.

I would like to promote E-week in California, USA. The Henry Samueli School of Engineering at the University of California, Irvine (UCI) is holding a giant celebration for E-week. Many events and competitions will be hosted by Engineering Student Council (ESC), which is an undergraduate organization that helps spread and promote engineering throughout the local community and mainly on the UCI campus. This year’s motto is “The Future is Not Written, it is Engineered”, and that couldn’t be more true. Everyone and anyone is welcome to al the events of E-week held on UC Irvine campus:

Tuesday, February 19

Dean’s Breakfast
Time: 9:30 AM to 11:30 AM
Location: Engineering Gateway (EG) Plaza

Wednesday, February 20

EngiTECH Career Fair
Time: 10:00 AM to 3:00 PM
Location: Engineering Tower / Computer Science Plaza

Pub Night
Time: 8:00 PM to 10:00 PM
Location: AntHill Pub

Thursday, February 21

High School Shadow Day
Time: 9:00 AM to 2:00 PM

E-Week BBQ
Time: 11:00 AM to 3:00 PM
Location: Engineering Gateway (EG) Plaza

Friday, February 22

E-Week Awards Banquet
Time: 6:30 PM to 9:30 PM
Location: University Club

Broomball!
Time: 12:00 AM - 2:00 AM (Friday night / early Saturday morning)
Location: Westminister Ice Arena

There are many more competitions that have prizes! If you enter and win, you can get up to $500!!

To find your way around the UCI campus, here is a Campus Map.

There will be hundreds of people at the e-week events include UCI faculty, undergraduates, and graduate students as well as many company representatives and hiring managers from over 50 different technical companies both local and international. Please come out and enjoy the events, free food, and networking opportunities!

Often in medicine, a situation may occur in which two patients have identical medical history and receive the same prognosis and treatment plan, however one of the patients does not respond to treatment. Traditional medicine works like this with protocols to follow for every patient. This has been extremely successful in the past decades, however researchers have discovered a new approach to improve the success of medicine. Since genetic variation is extremely common and often affects how one’s body responds to medication and therapy, researchers are working on incorporating each patient’s individual genetic profile into their treatment plan. This is called personalized medicine, which is a method in which diagnosis and treatment of a medical condition is catered toward the particular patient’s genetic profile to compensate for metabolic differences, seemingly silent mutations, and inactive viruses. Thanks to recent scientific advances in genomics (specifically the Human Genome Project), personalized medicine has the potential to provide patients with more advanced diagnostic testing methods. The sequencing of the human genome has made it possible for researchers to link many diseases and treatments to certain genes. These scientific advances make it easier to map molecular pathways, treat disorders, and understand how medication interacts with the body, thereby improving treatment protocols.

Figure 1: Although the government provides some barriers for personalized medicine, the Department of Defense has allocated increasing amounts of funds ($ in millions) towards The Human Genome Project. However, the majority of funding for the Human Genome Project research came from from NIH grants.

The majority of physicians prefer to stick to traditional trial-and-error medicine. Perhaps this is because of the great risk involved in trying new therapies when existing protocols are usually successful. Physicians who practice personalized medicine must create a unique treatment plan that takes into account the patient’s exceptional physiology, metabolism, and genome. Personalized medicine faces several boundaries, for example traditional physician practice, the pharmaceutical industry, the medical payment system and regulatory procedures. After personalized medicine can overcome these obstacles, much benefit prevails with this methodology such as saving more lives, reducing treatment costs, and improving patient recovery time through the accuracy, efficiency, safety, and speed that personalized medicine has to offer.

Obstacles of Personalized Medicine

Since personalized medicine is a new diagnostic approach that requires a good amount of training and studying to prevail in, there are many obstacles blocking its path to success. The most prominent barrier present is traditional trial-and-error medicine because it is extremely difficult to replace something that has been used for hundreds of years. Trial-and-error medicine has become a standard treatment process for doctors all over the world. It works in the sense that a patient presents typical symptoms, the physician provides a typical diagnosis, and then follows up with a typical treatment plan. When the treatment plan does not provide relief for the patient, the physician will go through this loop again and again until a diagnosis and treatment bring the patient back to being healthy. The problem with this type of protocol is that several treatments cost the patient more money and occupy an increasing amount of the patient’s time. The down-fall of this methodology is that the wrong treatment (although not occurring the majority of the time) can also lead to the patient becoming sicker, or even dying. One big reason for why physicians are not switching to personalized medicine is because many medical schools do not cover genomics and genetics completely in their curriculum, therefore graduating doctors may not understand the relevance and promise of incorporating their patient’s genome into their diagnosis. Personalized Medicine is very complicated and incorporates many specialties (figure 2) in order to serve the patient well, without a thorough education, physicians cannot be expected to take up this new protocol right away.

Figure 2: Personalized Medicine is a complicated health care practice which utilizes many fields and specialties.

Another barrier in the way of personalized medicine is the pharmaceutical industry. This is a helpful industry that has lead medicine along its way throughout history, however the pharmaceutical field has created a habit often referred to as the “blockbuster drug” model. A “blockbuster drug” is a product that is capable of achieving sales over $1 billion annually. In order to achieve these results, the product must be in wide enough use to earn this much revenue (i.e. a large number of patients should be using the product). Many patients, although they are the minority, suffer from adverse effects of largely prescribed medication and this can often lead to death. If the number of dying patients is statistically insignificant when compared to the amount of patients with no complaints, the pharmaceutical industry considers the drug of product economically favorable and continues production and distribution. This explains the fact that pharmaceutical companies are most profitable when they treat large populations of people with a given disease because the most profits come to industry when there are more consumers. Personalized medicine clashes with the “blockbuster drug” model because it incorporates each and every patient’s needs into a particular treatment plan, hence a small group of patients with similar treatment needs may not be supported by the pharmaceutical industry. As for drugs that are linked to diagnostics, pharmaceutical companies run in the other direction in fright that this may complicate the market to physicians and slow the identification and treatment of patients.

The reimbursment system that exists today is also working against personalized medicine. Medicare, Medicaid, and health insurance companies cover the majority of medical costs. These reimbursement institutions provide financial support for each procedure conducted. Therefore, rather than spending time to correctly diagnose a patient, physicians are often pressed for time to squeeze as many procedures into their schedule as possible for the most economic gain. If companies develop new and improved diagnostic testing methods to help physicians more accurately diagnose their patients, perhaps physicians would be more likely to provide their patients with the proper treatment plan.

The most popularly despised barrier of personalized medicine is the world of regulatory affairs, referred to as the FDA (Food and Drug Administration) in the United States. The current regulatory system is not economically feasible with the way that personalized medicine works, however the FDA is not in opposition to personalized medicine. Since clinical trials of drug-development costs are high, it takes much time to pass the safety and efficiency of new drugs. If a certain drug pertains to a small percentage of patients (as in personalized medicine), a clinical trial may not be cost effective enough to put that drug through the FDA process. In the FDA’s support of personalized medicine, Dr. Andrew Von Eschenbach, Director of the FDA, gave a briefing to the Personalized Medicine Coalition at the National Press Club. He announced that the FDA is working on ways to bring new testing and treatment methods to the molecularly-based market. On the other side of regulatory affairs lies the U.S. government. Despite what many citizens may think, the government is quite involved with this scientific advancement. Since very few genomics-based tests and treatments are available to consumers, government officials have been taking a stand to support personalized medicine. For example, Senator Barak Obama introduced the Genomics and Personalized Medicine Act to overcome scientific barriers by promoting medical advancements to regulatory obstacles. Mike Leavitt, United States Secretary of Health and Human Services, has created a committee called the Secretary’s Advisory Committee on Genetics Health and Society. A specific committee dedicated to updating government officials on genetic health and advancements is a big step in the direction of personalized medicine. Although regulatory obstacles do exist, there are also steps being taken to help medical advancement towards personalized medicine.
Advantages of Personalized Medicine

Patients with acute or fairly progressed diseases do not have the comfort of time that it takes for traditional trial-and-error medicine. If the first diagnosis and treatment plan doesn’t work, it may be too late to save the patient. As you can see in figure 3 below, symptoms progress and diseases worsen quickly and many patients don’t have the luxury of time that it takes for traditional medicine to treat them. By utilizing the patient’s unique genome and identifying which treatments are sure not to work, personalized medicine can save this patient much sooner than traditional medicine. If the patient is treated sooner, their bed and room in the hospital may open up in time to save another patient’s life. Saving time is crucial to the patient, the hospital, and physicians alike.

Figure 3: Shows the relationship and correlation between time, disease management of traditional trial-and-error medicine, and disease progression.

With that said, less treatment therapies used means less money spent. Personalized medicine has the potential to save each patient thousands of dollars. The FDA estimates that if diagnostic tests based on genomics were used on just the patients needing warfarin, the United States health care system could save as much as $1.1 billion dollars every year. These types of tests are currently available and can be used hand-in-hand with personalized medicine to refine each patient’s treatment plan; unfortunately these tests are underused. If each physician were to routinely utilize these diagnostic methods, they could save billions of dollars by just avoiding adverse patient reaction to the inaccurate treatment.

Researchers are currently trying to trace metabolic pathways, genetic variants, and treatment resistance in the human genome. Once each of the three are linked together, they will develop diagnostic tools for each situation. The advantages of personalized medicine are enormous, however there are many difficult road blocks to overcome before personalized medicine can hit the mainstream. The people fighting for personalized medicine, like the Personalized Medicine Coalition (PMC), need to work harder and faster to get it over the hurdles, but most of all they need more support. Personalized medicine is for YOU and you only, so do a little work for it.

For further information on Personalized Medicine: FUSE, Realizing the Promise of Personalized Medicine, MayoClinic, and Pharmacogenomics.

What is Atherosclerosis?
Atherosclerosis is a disease where lipoproteins, which are plasma proteins that carry triglycerides and cholesterol, collect on the inner wall of arterial blood vessels. It is a chronic inflammatory response in the walls in which the lipoproteins harden and form plaque within the arteries. There are three different types of atheromatous plaque. One type is simple cholesterol crystals that build up along the wall and narrow the diameter of the artery. The second type is called an atheroma, which is a nodular accumulation of flaky, yellow material (which is composed mostly of macrophages) in the center of large plaques at the lumen of the artery. The last type of atheromatous plaque is calcification of the outer base of more advanced lesions.

Atherosclerosis is caused by many factors, some of which can be controlled by the patient. Hypertension, obesity, smoking, diabetes, high cholesterol, and congenital heart disease can all be individual or combined causes of atherosclerosis in a patient. Depending on where in the body plaque builds up, symptoms may include angina, heart attack, severe pain, stroke, and/or dizziness.

Significance of Atherosclerosis
Atherosclerosis progresses slowly and is cumulative over time, beginning with macrophage infiltration into the artery. A fatty streak results and a lesion advances to eventually create an atheroma, as shown in the figure below. This continues to advances to create a larger, more complicated lesion. Over time, if the lesion is not treated, the plaque will suddenly rupture and form a thrombus that severely slows down, or even stops blood flow. This can lead to an infarction, which is death of the tissues feeding off of the artery within five minutes if it is not tended to immediately.

In the United States alone, atherosclerosis leads to the death of almost 15,000 people every year. It is also the cause of hospitalization for 20,000 patients per year and over 730,000 physician office visits per year.

Current Treatments
Current treatments include improvements in diet, cholesterol reduction medication, anticoagulate medication, blood pressure medication, surgical procedures and sometimes even gene therapy. Our medical device plans to make improvements upon the current surgical procedures, which are endarterectomy, angioplasty, bypass surgery, and thrombolytic therapy.

In my previous article, The Basics of Heart Failure, it was mentioned that a ventricular-assist device (VAD) is the primary treatment for heart failure. Dr. William Wagner (who also contributed to the positive displacement pump technology previously mentioned) believes that there is much room for improvement in the biocompatibility of VADs. he spoke at the BMES conference of infection and thrombosis (blood clotting) problems upon implantation of VADs into patients.

Infection due to VADs can be caused by the biomaterial used, poor sterile technique, device failure, and percutaneous line design. Shear forces caused by excessive bleeding upon implantation of the device can also cause infection, and infection leads to tissue necrosis.

Thrombosis and thromboembolism are problems that all devices face when coming into contact with blood. To avoid this issue, surgeons use drugs like Heparin or Coumadin to avoid coagulation when devices come into direct contact with the blood.

Many scientists believe that nothing can be solved unless it can be quantified. Infection and thrombosis (believe it or not) can be crudely measured through microembolic signals (MES). Dr. Wagner suggested that scientists should get more out of animal models by analyzing MES, explants, and gross neurological health more thoroughly to minimize plately aggregation and avoid thrombosis. An example of a thoroughly tested device that has been underway for 30 years is the Heartmate II, which is implanted in the chest to aid the heart in pumping (shown in the figure above). This device can be used as a treatment method for patients with severe heart failure, or as a bridge until a transplant is available. When tested in calves, this device showed a spike in platelet aggregation (which is expected and normal) and then a steady decrease in aggregation due o microaggregates leaving the implant site. In previous VADs, the platelet aggregation spiked and then didn’t decline at a steady enough rate for thrombosis to cease. Another research project underway by EvaHeart to improve the downfalls of VADs is to replace bovine (cow) with ovine (sheep) products due to this superior configuration of ovine tissue (methacryloyloxyethyl phosphorylcholine).

-Amy

Heart failure (HF) is a condition in which the heart’s ability to fill or pump a adequate amount of blood is impaired. It can be caused by a number of factors including hypertension (high blood pressure), valve failure, coronary artery disease, and many more things. In the figure below, heart failure is shown to be caused by thickened myocardium (myocarditis), which may be a direct result of a viral infection that can cause the muscle to become inflamed. Almost 2% of the American population has heart failure and even with the best therapy, HF still has an annual mortality of 10%.

Treatment of HF depends on the stage of the disease’s progression and is rated on a scale from case I to case IV. The five year survival rate of patients in stage IV is only 20%, therefore this is considered severe heart failure. There are several minimally invasive devices used in HF treatment. The most common treatment device is an artificial pacemaker (shown below), which successfully prevents about 50% of all heart failures from re-occurring. Another treatment option for HF that is extreme is a heart transplant. This is called the “Gold Standard” treatment because it is the best to use, however the availability of donors is slowly declining while the number of patients who need a transplant is steadily rising. Only about 2200 heart transplants are preformed every year.

The ideal solution would be an artificial heart…In 1985, at the University of Pittsburgh Medical Center (UPMC), the first artificial heart was implanted. Five years later, UPMC was the first medical institution to release a patient with a ventricular-assist device (VAD) (shown below). Today, VADs called positive displacement pumps are the leading treatment therapy for HF patients. Dr. Marc Simon presented the idea of positive displacement pumps at the BMES Conference and spoke of future improvement for these devices. He announced that second and third generation prototypes are currently underway in many institutions and will be ready for release soon. Dr. Simon discussed that there is an ideal period during HF in which it is ideal to implant there devices into the patient in order to maximize recovery success. There is a certain point in HF in which an acute, catastrophic event leads to sudden progression of the disease, eventually leading the patient to death. The closer researchers are able to pinpoint the time immediately prior to this turn of events to implant the device, the greater the patient’s chances are for survival.

-Amy

When preforming surgeries, an obstacle that has to be dealt with is making sure that the patient;s blood doesn’t coagulate (or thicken) when it comes into contact with metal intruments. This is currently dealt with by a drug called heparin, which thins the blood so that it doesn’t have an adverse reaction to the touch of an instrument. Heparin is widely used and is successful…most of the time. It creates negative reactions in three to ten per cent of all patients in which the blood will coagulate and clot up all around an instrument as soon as direct contact is made. The image below shows that when Heparin fails, coagulation occurs and the device used in surgery is covered with blood clots:

At Brigham Young University, BYU, an alternative solution has been found. Dr. Kenneth Solen and Jared Parker, biomedical engineers who have dedicated much time to this problem, believe that a different type of precaution needs to be taken. They suggested that rather than adding something to the blood that may induce an immune reaction, they would like to remove something. There exist specific proteins in the blood that carry a strong electrical charge in order to cause coagulation. One could conclude that to remove these proteins, something with a negative charge must be utilized. Therefore, the research team used a negatively-charged gel to attract and remove these coagulation proteins, while leaving the rest of the neutral and negatively-charged proteins in the blood. In the lab, this was proven to be successful, however human testing has not been conducted yet. Dr. Solen continues to pursue the perfection of this innovation at W.L. Gore.

After Dr. Solen’s anticoagulation method, the device used in surgery remains clear of blood clotting:

I would like to thank Blake Ferguson for sharing this article with me.

-Amy

Drugs are used in numerous medical applications, such as improving the patency of a stent, cancer treatment, and infection control. Although drugs are used to treat an injury or alleviate pain, many of them will have adverse side effects if the drug is administered systemically (throughout the entire body). Once drugs are administered, they are nonlinearly absorbed into the body and result in only acute (short term) effects. For this reason, a method of chronic (long-lasting or long-term) and localized drug delivery would be advantageous to treating the area of interest without causing adverse systemic effect. The two main variables that need to be controlled are drug dosage and timed release of the drug. Many methods, such as polymer blends and biodegradable capsules, have been attempted to gain maximum control of these two factors. However, both variables have been proven to be controlled effectively through light-initiated drug delivery.

At Queen’s University, Belfast in Northern Ireland, Dr. Colin McCoy and his fellow researchers developed medications combined with photosensitive chemicals. When light falls upon the site of the body where the drugs are present, the drugs will slowly begin to release into the body. The drug release stops whenever the light is turned off or not shining directly on the site. The group’s main goal was to create a drug delivery method with minimal side effects for patients. This method also leads to more controlled drug dosage, better time release, and a cheaper drug delivery option for patients.

Although pacemakers are usually associated with the heart, Medtronic has developed a pacemaker attached to two electrodes to induce deep-brain stimulation for minimally conscious coma patients.  Figure 1 shows an x-ray image of the device in a patients head, notice how deep the device must be in order to stimulate the brain sufficiently to wake someone from a coma.  Patients with severe brain injuries often slip into comas for the rest of their lives and are more than often thought of as “gonners”.  This success story from Chicago could change the way modern medicine sees these victims.  The plan is to test the device in 12 more patients and then move on to the wide-spread clinical applications thereafter.

Figure 1

-Amy Shah

Coronary Artery Disease and Coronary Bypass Grafting

Coronary artery disease (CAD) is the leading cause of death for both men and women in the United States. The process of atherosclerosis is the hardening of an artery due to a lipid build up, resulting in functional loss. Fatty deposits, or plaques, may accumulate inside the arterial wall and cause stenosis, or an abnormal narrowing the artery wall. This causes the flow of blood to be reduced or completely stop and the vessel wall to lose its flexibility and ability to handle pulsatile flow. There are several forms of treatment available for CAD depending on the severity of the disease, including lifestyle changes, medicines, angioplasty, and coronary artery bypass grafting (CABG).

CABG is the preferred treatment for patients with multiple areas of coronary artery narrowing or blockage and also for patients with higher percentages of stenosis, this relation can be seen in figure 1 above. Patients typically have 1 to 5 bypasses within one surgical procedure. This form of treatment is the most common type of surgery in the United States, with about 500,000 surgeries per year. Typically, the patient’s saphenous vein from the leg, internal mammary artery (IMA), or the radial artery from the arm is used. Figure 2 shows the location of the saphenous vein and IMA. These vessels are removed and grafted onto the hardened artery to revascularize the affected area.

Figure 2

Advantages and Disadvantages of the Current Gold Standard

The current gold standard for the CABG procedure is the use of autologous (from self) saphenous vein and IMA because of their resemblance to the native coronary artery and their relatively high patency rates. It was not until recently that the radial artery has been widely studied as another source for this procedure. The five and ten year artery patency rates for these have all shown to be greater than 70% and 50%, respectively. These rates vary depending on the blood vessel used for the procedure.

Even with the success this procedure has had, there are several disadvantages that may lead to complications. Removing an autologous vein for the procedure may cause donor site morbidity, which can lead to problems such as groin infection near the site of the saphenous vein removal. In addition, there is only a limited supply of donor vessels for this procedure. Up to 30% of patients undergoing lower limb bypass do not have a suitable vein. This can be problematic for patients who need multiple CABGs or have had previous procedures. There is also a greater risk with the use of multiple vessels. For example, there are more incidents of deep sternal wound infection when both IMAs are used for this procedure, especially for patients with obesity and diabetes.

Existing Vascular Grafts and Improvements

Although living autologous vessels seem to be the ideal conduits for CABG, there are several factors, as discussed above, which have prompted efforts to develop a more suitable donor vessel. The ideal blood vessel substitute should mimic the characteristics of a native blood vessel, including its composition, structure, function, and mechanical properties. It should be durable enough to endure the mechanical stresses, as well as the threat of biodegradation and infection within the body after implantation. The vessel should be made up of materials that promote cell-specific interactions and needs to be able to have similar viscoelastic properties as a normal artery to avoid a compliance mismatch. It should be flexible in order to maintain its contour, yet rigid enough to prevent kinking. The materials used, especially on its luminal surface, must be nonthrombogenic to prevent blood clotting in the vascular graft. It is favorable that the vessel is easily and quickly manufactured, and should be readily available in multiple lengths and sizes.

However, no existing conduit possesses all the properties and qualities of the ideal arterial vascular graft listed above. Current alternatives to autologous vascular grafts are prosthetic conduits based on expanded polytetrafluoroethylene (ePTFE) and polyethylene terephthalate (Dacron ®). Their patency at 5 years is 40% to 50%, which is acceptable but relatively low. Tissue engineering has proven to be successful in wound management, burns, and cartilage repair; therefore their has been a growing interest in designing biological blood vessels as an alternative to autologous vascular grafts and current prosthetic conduits. However, previously proposed and designed tissue engineered vascular grafts were not durable, were prone to early thrombosis, and had poor patency rates. This means that a new vascular graft with all the above mentioned qualities is yet to be manufactured, but is a hopeful potential cure for the future.

Everyone knows that science has been booming at an insanely quick rate for the past decade. The world has erupted with stem cells, tissue engineering, cures for diabetes and Alzheimer’s Disease all in the past ten years! But what about the next ten years? MSNBC predicts that stem cells will be the norm, tissue engineering will be a replacement for most major surgeries with the remaining surgeries to be preformed by robots, and cures to widespread diseases will be perfected. If you’re not very fond of reading, watch this video The Year 2017 and get a glipse of what is to come (the video will play after a 30 second commercial).