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Getting The Public Invested In Science

FundScience Blog

Welcome to the FundScience Blog. This page was created to bring you the news of our venture by the FundScience team (Category: FundScience News) as well as interesting subjects that are related to education and science. We welcome and encourage comments and discussions on the posted topics. If you are a writer and are interested in posting please contact us. If you are a reader we hope that you sign-up for a feed of our blog and/or a quarterly collection of the published articles in an easy to read and pass to friends PDF format.

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The FundScience Team

The White House Office of Science and Technology Policy Needs our Help!

05.7.09 by Daniel Gaddy

I received the following information from Sciencedebate.org. Over the past several months, and again last week at his address to the National Academies of Science, President Obama pledged to restore scientific integrity to government. Of course, that is easier said than done. Apparently Obama recognizes this, and has asked for input from us, the concerned public.

On March 9, the president formally asked the White House Office of Science and Technology Policy (OSTP) to make recommendations on how the executive branch can meet this pledge.

The OSTP has opened a public comment period regarding this directive, giving you the opportunity to share your thoughts on what the next steps should be.  Comments are due by Wednesday, May 13.

The OSTP is looking for recommendations on the six issues President Obama identified in his memo:

  1. hiring and keeping qualified scientists
  2. defining new policies to ensure integrity
  3. using “well-established scientific processes” like peer review
  4. disclosing scientific findings
  5. ensuring that principles of scientific integrity are being adhered to
  6. adopting additional policies like whistleblower protections

The OSTP is accepting comments via email and through their blog, here.

Their original request for input can be found here (pdf).

Many organizations in Washington will be giving their opinions of what the OSTP plan should entail.  We believe it is important for scientists and other science supporters to be included in that process, and for you to indicate to the White House how science and scientific integrity affect your work, your families, and your communities.

If you’re interested in more background information, visit the scientific integrity site of our friends at the Union of Concerned Scientists here.

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Influenza A(H1N1)

05.4.09 by Daniel Gaddy

A media firestorm has been unleashed over the last few weeks regarding the so-called “swine flu.” If you pay attention to CNN or any mainstream media outlet, you are bombarded with dire warnings and panic-inducing reports of swine flu deaths and the resulting mayhem. I want to write this post to put things into perspective. Keep in mind that the news outlets have one thing in mind: ratings. The more fear they can strike into you, the more likely you are to watch. This is not to say that there is no reason to be concerned. As with any influenza outbreak, the more you know, the better prepared you are to handle it. However, the media consistently compare the current outbreak with previous pandemics, particularly the 1918 pandemic. The chances of such a disastrous pandemic are rare. Here, I will explain why that is, as well as provide some insight into this disease and some resources that will help you prepare should you come into contact with anyone infected with influenza.

First of all, the nomenclature “swine flu” is inaccurate. I am not saying this because I have been paid by the pork lobby. The truth is, this virus is part swine, part avian, and part human. This description is, in and of itself, probably confusing for a lay-person. Influenza virus biology is too complicated to get into here in real detail. Basically, influenza virus has a segmented genome. These segments are similar to chromosomes in humans, in that they are nucleic acids (RNA in the case of flu) and each segment codes for a different viral protein. The process of segments from different strains of virus (eg. swine, avian and human) coming together to form a new strain of virus is called re-assortment. This occurs when multiple viruses infect the same cell, and a basic example is illustrated in the figure below. This process occurs frequently, particularly in animals such as pigs and birds, but rarely results in super-virulent strains of influenza.

Influenza Re-Assortment

Influenza viruses are further subdivided based on their surface proteins, hemagglutinin (HA) and neuraminidase (NA). To date, 16 unique HA subtypes (H1-16) and 9 unique NA subtypes (N1-9) have been identified. The virus in the current outbreak has subtypes H1 and N1, leading to the appropriate Influenza A(H1N1) designation.

When thinking about outbreaks of viruses such as influenza, which occur annually, it is important to maintain a level head and not fly into a frenzy, as it seems the mainstream media would like for you to do. When the Vice-President of the United States goes on television and essentially tells people to not go outside and to avoid crowded places, it not only demonstrates his ignorance on the subject, but spreads that ignorance to everyone who listens to his nonsense. This causes undue panic, and makes people think they may die just by getting on a bus, subway or airplane. The truth is, no one really knows how serious this outbreak will be. But to compare it to the 1918 influenza pandemic, largely because they both happen to be H1N1 strains, is ridiculous. By all estimations, the 2009 outbreak is already a pandemic, as cases have been reported around the world. A map of laboratory-confirmed cases is shown in the next figure.

However, a pandemic only means that cases have been reported in various countries around the world. It by no means suggests that this disease is going to be as severe as the 1918 virus. It is estimated that between 70 million and 100 million people died in the 1918 pandemic. So far, only 26 people have died worldwide as a result of this virus, 25 in Mexico and 1 in the United States. Compare these figures to the annual death toll caused by “regular” influenza: in the United States alone, more than 36,000 deaths occur annually as a result of influenza, and between 250,000 and 500,000 deaths occur worldwide. Clearly, the 2009 Influenza A(H1N1) virus has a long way to go to reach either of these statistics.

In my opinion, for what it is worth, it is unlikely that this virus reaches anywhere near the severity of the 1918 pandemic. First of all, the disease reporting is far better today than in 1918. When cases occur practically anywhere in the world, those cases are reported and everyone around the world knows about it quickly. A disease as severe as the 1918 influenza is not going to sneak up on us. This gives us time to prepare. One of the good things that has arisen from the media firestorm is that people are taking the outbreak seriously enough to go to the hospital as soon as symptoms arise. While there is no cure for influenza, early treatment is key to preventing the development of severe complications due to influenza infection. Furthermore, we actually know how to care for patients now, unlike in 1918. A virus would have to be extremely virulent to cause as many deaths as the 1918 flu, and this virus has thus far given no signs of being that virulent.

Finally, there are a number of things everyone can do to reduce your chances of becoming sick and to avoid spreading the infection to others. This may be boring, but it is important. First and foremost, wash your hands! This seems so basic, yet it seems that people must be constantly reminded. If you are in a crowded place, be it a bus, subway, etc, the first thing you should do when you reach your destination is wash your hands. Other people carry a variety of germs, not just influenza, and the primary means of contracting these germs is to touch a contaminated surface, then touch your face. So wash your hands! Secondly, get the annual flu vaccine. It will not protect you from this ongoing Influenza A(H1N1) outbreak, but it typically does a very good job of protecting against the very serious seasonal flu virus that kills over 36,000 people annually in the US.

Symptoms of influenza infection are:

  • fever (usually high)
  • headache
  • extreme tiredness
  • dry cough
  • sore throat
  • runny or stuffy nose
  • muscle aches
  • Stomach symptoms, such as nausea, vomiting, and diarrhea, also can occur but are more common in children than adults.

If you experience these symptoms, seek medical treatment. If treated early, antiviral therapeutics may help reduce the severity of the disease. After seeking treatment, avoid crowded places so as not to spread the infection to other people. When you cough or sneeze, cover your mouth and nose with your arm, not your hands. If you sneeze in your hands then touch something, other people may come along and touch the same surface, thereby risking transmission of the virus.

The bottom line is, no one knows how severe this outbreak of influenza will be, but influenza is always serious! However, by thinking rationally and following some basic, common sense principles, we can aid in reducing the severity of this outbreak and others.

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Earth Day

04.22.09 by Daniel Gaddy

Today, April 22nd, is Earth Day, the one day every year that we stop to think about how our irresponsible actions are affecting the planet. We spend this day pondering the ways we can change our behavior and save our planet, so that tomorrow we can go back to life as usual. But as the planet grows warmer, the ice continues to melt, the oceans continue to rise and the levels of toxic gases in the air continue to rise, it is time we start spending more than just a day thinking about these issues. Denying the existence of global warming is akin to denying the existence of evolution – or clouds. It is undeniable. Moreover, mounting scientific evidence indicates that global warming is the result of human action. Over the past century, the release of carbon dioxide and other heat-trapping gases from smokestacks, tailpipes and burning forests has played a central role in raising the average surface temperature of the earth by more than 1 degree Fahrenheit. That may not seem like a lot, but if you consider what it takes to raise the temperature of the entire planet by even 1 degree, it is frightening. So, we can spend the rest of our lives sitting around talking about it, but what can we actually do about it? Well, until the government actually enforces stricter emissions regulations, we as individuals can make small changes in our daily lives that can make a difference. These small changes may include changing all of your incandescent light bulbs to more energy-efficient compact fluorescent light bulbs. Try actually turning your lights and electronic devices off when you are not using them. Buy energy- and fuel-efficient appliances and cars. Drive your car less – walk more, use public transportation when you can, and car pool. Reduce your waste and recycle everything you can. Most of these changes can actually save you money, as well as make you healthier. As important, spread the word – educate your family, friends and neighbors on the dangers of climate change and the benefits of going green. Find more ways to go green in the Related Articles section below. Share ways that you have gone green in the comments.

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Introduction to Evolution

04.17.09 by Daniel Gaddy

February 12th, 2009 was Charles Darwin’s 200th birthday. That weekend, I had dinner with some friends, most of whom are scientists. I mentioned Darwin’s birthday and, being scientists, we raised our glasses and toasted Darwin. However, one of the ladies at the table, who is not a scientist, objected and said that evolution is just a theory and she doesn’t believe it. She was the only person at the table to hold this opinion, and much of the night was spent trying to convince her otherwise. Her primary stumbling block was her belief that evolution is an entirely random process, and she did not believe that ever-increasing complexity could arise by chance. There are a variety of things wrong with her idea of evolution, and what I quickly realized is that she simply did not understand evolution. Worse yet, I quickly learned that a table full of scientists could not do a sufficient job of explaining it to her! This led me to ask myself a couple of questions. First of all, how many people out there accept evolution without fully understanding it? Secondly, how many people do not believe in evolution because they simply do not understand it? Therefore, I decided to write this blog post as a simple introduction to evolution. Universities offer entire courses focused on explaining evolution. This post is not meant to substitute for a 4-month college class. Instead, I simply aim to address the basics of evolution and some of the common misconceptions.

In 1859, 150 years ago, Charles Darwin published On the Origin of Species, one of the most important and influential books ever written. In it, Darwin introduced his theory of evolution, which itself evolved over the course of Darwin’s 5 year journey around the world on the HMS Beagle, and in the subsequent years studying his notes from the journey. At its core, Darwin’s theory established a scientific explanation for diversity in nature. A minimal working definition of evolution is “a process that results in heritable changes in a population spread over many generations.”

Webster’s dictionary defines evolution as, “the development of a species, organism, or organ from its original or primitive state to its present or specialized state; phylogeny or ontogeny.” Definitions such as this one are inaccurate for a number of reasons. First, they imply that modern species/organisms/organs arose in their present form from original or primitive species/organisms/organs. This leads to anti-evolutionists saying things like, “I didn’t evolve from a monkey!” They are absolutely right! They did not evolve from a monkey. The primary problem with such definitions is that they ignore the most important parts of evolution, thus leading to a great deal of confusion. It is absolutely necessary to underscore the point that evolution is a gradual process, “spread over many generations.” It is absolutely necessary to point out that evolution “results in heritable changes,” meaning that the changes are genetic and can be passed from one generation to the next. Finally, it is imperative to point out that evolution applies to entire populations, not individuals.

Such inaccurate, but widely touted, definitions have given rise to many misconceptions of evolution. Many of these misconceptions have been dealt with elsewhere, and I encourage the reader to continue learning about this process by exploring the links and Related Articles section below. While I may be accused of oversimplification, I will now attempt to address a few of the most common misconceptions of evolution.

First of all, I will address my friend’s belief that evolution is entirely random. In fact, evolution may be considered a two-step process. It is true that there is some degree of randomness. The first step of evolution is the introduction of genetic mutations, which occur by chance or randomness. However, mutations constantly arise and the vast majority of mutations are lost. For a mutation to take hold and be passed on to subsequent generations, it must provide some advantage. This is part of the process of natural selection, or the second step of evolution. Natural selection is tightly regulated by the environment, and is anything but random.

That being said, natural selection is only a piece of the puzzle. If we ignore chance events, we are ignoring a large part of the process of evolution. As I said, mutations are constantly occurring, due to a multitude of factors. In fact, every human embryo contains at least 100 new mutations. Some of these mutations may be harmful and may be lost during natural selection, often resulting in death of the embryo. However, most mutations are neutral, meaning they provide no positive or negative influence. When a mutation is beneficial and passed along, or is harmful and lost, that is natural selection. If a mutation is neutral and is passed along, as will happen simply because there are so many neutral mutations, that is an example of random genetic drift. A specific example of genetic drift in a population is eye color. Humans, and other diploid organisms, have two copies (alleles) for each gene. In the case of eye color, if a person has brown eyes, they may have a brown allele and a blue allele, but brown is dominant and will be expressed while blue is recessive and not expressed. However, either the brown or blue allele can be passed on to offspring, creating the possibility that two brown-eyed parents can have blue-eyed offspring. In effect, genes of offspring are a random sampling of parental genes.

Another misconception voiced by my friend is that evolution leads to ever-increasing complexity. It is certainly true that evolution has produced a multitude of complex organisms, including humans, and this complexity is due in part to natural selection. However, recent research has led to a competing hypothesis, suggesting that increased complexity actually results when selection is weak or absent. In essence, this hypothesis suggests that weak selection may allow for things such as duplicate copies of genes, which may arise due to genetic drift and be weeded out when selection is strong. For instance, there is a great deal of evidence that some modern, “simple” species have actually evolved from more complex ancestors. Examples include many species of cavefish and other organisms that live in the murky depths of the ocean, which have lost their eyes due to natural selection. Living constantly in darkness, these organisms no longer needed their eyes. As other traits gradually evolved to aid survival in darkness, unnecessary features such as eyes gradually disappeared, illustrating that evolution giveth, and evolution taketh away.

Counter to the above misconception, many people also believe that evolution is unlikely to produce complexity. This view is often the result of the failure to understand the time necessary to produce complex organisms, and is another example of the confusion that can arise from inadequate definitions of evolution. It is true that a single mutation, or even a series of mutations, is unlikely to produce more complex organisms. But more complex organisms do not typically arise in a single generation. The evolution of complex organisms requires multiple generations. Life on earth, as we know it, has evolved over billions of years. The process has involved countless mutations, many of which have been positively selected, and many more of which have been eliminated. It is important to remember that natural selection is not intrinsically progressive, meaning it does not tend toward more complex organisms. Populations are selected for either increased or decreased complexity in response to local environmental conditions.

Another misconception is that natural selection always promotes the survival of species. In fact, natural selection applies not only to populations of organisms, but also to genes. While it may be difficult to comprehend, positive selection of genes can actually be detrimental to the whole organism. Examples include transposons, which are positively selected DNA elements that can cause genetic diseases such as hemophilia. Multiple other examples exist and are given a more thorough treatment here. It is important to note that evolution is not always a constructive process. While we are surrounded by examples of successful species, countless others have failed, resulting in extinction of species.

The last thing I would like to address is the teaching of evolution in this country. Much of the rest of the developed world accepts evolution more than the United States. To some degree, this is likely the result of religious influence. It is no surprise that the more devout a person, the less likely they are to believe in evolution. These beliefs have a tremendous influence on our politics and, thus, our education system. Therefore, the treatment of evolution in our schools is often meager, at best, and many states continue to push the teaching of intelligent design/creationism as a realistic alternative. The map below is from a 2002 Scientific American article and illustrates how and where evolution is taught in the US.

As you can see, as recently as 2002 only a handful of states received “Very good/excellent” ratings. For the record, I received a pretty good science education in a North Carolina public school, including the teaching of evolution. I distinctly remember that one of my favorite biology teachers, while teaching evolution, was asked by another student if she believed in God. The teacher said she did, but chose to believe evolution was God’s plan. That teacher was an example of someone who found a balance between her religious views and her scientific views. She did not let her religious beliefs mar her scientific views, and she did a good job of teaching evolution. Many other students are not so lucky.

There are those who argue that evolution is just a theory and has not, or even cannot be, proved, so should not be taught. In fact, evolution is supported by overwhelming evidence that has accumulated over billions of years. As a virologist, I see evolution on practically a daily basis. In fact, you can watch the process of evolution almost daily in any microbiology laboratory in the world. Viruses and bacteria, as examples, are constantly evolving. The process of natural selection leads to drug-resistant bacteria and the new strains of influenza virus we see every year, which make us create a new flu vaccine every year.

There are also those who say that it doesn’t matter whether or not we accept evolution. Believe it or not, evolution impacts our lives. People who do not understand, or choose to deny, the mountains of scientific evidence supporting evolution are all too often the people making decisions that affect the rest of us. A rejection of evolution is a rejection of basic science principles. These principles have shaped not only our country, but the entire world. To reject these principles is to deny our history, and to impede our future.

While this post is intended to be a simplified overview of evolution, I want it to be as accurate as possible. There are far too many inaccurate accounts out there, and this should not be yet another one. Therefore, if you believe that I have left out something particularly important, or that I have not given a proper treatment to any of the topics, please let me know in the comments. Similarly, if you would like additional clarification on anything I have written here, please do not hesitate to ask questions in the comments. This blog is, above all, a place for education.

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Bail Out the Education System!

04.3.09 by Daniel Gaddy

Recently, a lot of discussion has taken place about Wall Street and automotive company bailouts. Another bailout, a worthy one, is beginning to finally get some press. It is not breaking news that the education system in the United States has struggled for some time now, particularly when compared to the education systems of other nations around the world. According to a Washington Post article published late last year, as the cost of college soars, the United States is lagging behind much of the world in terms of providing access to higher education.

During the past two decades, some other nations have made the kind of effort to improve access to higher education that the United States undertook in the 1950s, ’60s and ’70s, said Patrick Callan, president of the research group.

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In the United States, by contrast, college costs keep rising; more students are dropping out of high school; and large gaps remain in the success rates of students of different races, incomes and states. “We’re one of the few countries where our older population is better educated than the younger population,” Callan said.

The study gives a failing grade for college affordability to every state but California, which received a C because of the relatively low cost of its community colleges. Researchers said the percentage of an average family’s income needed to pay for a public four-year college has risen from 20 to 28 percent, after financial aid. For community colleges, the burden has risen from nearly 20 percent to nearly 25 percent.

…In the past decade, student borrowing has more than doubled, and as the economy worsens, the researchers warned, many states have predicted cuts in higher education funding.

Since the early 1980s, college tuition and fees have jumped nearly 440 percent, far more than health-care, food, housing and transportation costs. The median family income rose less than 150 percent.

So, while we can pour as much money as we want into the current economic crises, the failure to fund and improve our education systems means one thing: our future generations will be grossly unprepared to compete with their better-educated, better-trained, and overall superior peers from around the world. What does that mean? The financial “crisis” we are experiencing today may be nothing compared to the crises we may face a generation or two down the road. Imagine unemployment soaring as Americans can’t get jobs because they can’t compete with superior foreign applicants. Imagine our economy crumbling as companies leave our shores for better opportunities in Europe or Asia.

To some degree, this is already happening, particularly in the sciences. A recent UK study revealed that only 28% of British 16-18-year-olds believe that science is a relevant career choice, and no survey is needed to see that similar attitudes prevail in the United States. The majority of Postdocs and Graduate Students I work with on a daily basis and interact with at meetings are Asian, mostly from India, China and Korea. The reason is simple: science is still perceived as a meaningful, dignified, and, perhaps most importantly, well-paid career choice in these countries, while the negative stigmas that are associated with science in much of the western world are nowhere to be found. A lot could be said about the lack of funding for science in the US and the poor salaries scientists endure compared to the enormous time we put into our education and careers. What I want to talk about here is the education process. The negative stigmas associated with science are ingrained in our youth early: science is too hard, not interesting, not fun…. It is true that science is hard, but it most certainly is interesting and fun! We can change these perceptions with early education. Science is all too often presented as boring and stuffy, and the image of a scientist is the disheveled, lab coat-wearing Einstein look-alike. Who can blame kids for immediately coming to negative conclusions. When taught properly, science can be seen as an interesting series of puzzles, in many ways like a game, but potentially a game of life and death. Depending on the field of science, of course, there may be good guys and bad guys (the good guys being the scientists and the bad guys being, for example, deadly diseases the scientists are trying to cure). There is a great deal of strategy involved in defeating the villains, as there is in the most popular video games of today, which kids (and many scientists I know) devote almost all of their free time to playing. In the end, if presented properly, the difficulty involved in science can actually be a good thing because it provides a challenge, and we all know that kids are quickly bored by easy games. This analogy may be tedious, but it makes sense to me.

But all of this is for nothing if our education system continues to fail our youth. Therefore, the bailout of the education system is a bailout I can firmly stand behind. Of course, simply throwing money at a problem never actually solves the problem. Our education system needs an overhaul on a variety of fronts, but an affordable education must be a top priority.

Robert Reich provides more justification for bailing out the education system:

It’s absurd. We’re bailing out every major bank to get financial capital flowing again. But we’re squeezing the main sources of our nation’s human capital. Yet America’s future competitiveness and the standard of living of our people depend largely our peoples’ skills, and our capacities to communicate and solve problems and innovate – not on our ability to borrow money.

What’s more, our human capital is rooted here, while financial capital moves around the globe at the speed of an electronic blip. Right now global capital markets are frozen, but the big money — mostly in Asia and the Middle East — and will come here, bailout or no bailout. At this point it’s coming back as purchases of dollars or in the form of T-bills that are financing the Wall Street bailout. Eventually American assets will become so cheap that the money will come rushing here to buy up the bargains.

It’s our human capital that’s in short supply. And without adequate public funding, the supply will shrink further. Don’t get me wrong: I’m not saying funding is everything when it comes to education. Obviously, accountability is important. But without adequate funding we can’t attract talented people into teaching, or keep class sizes small enough to give kids a real chance to learn, or provide them with a well-rounded curriculum, and ensure that every qualified young person can go to college.

So why are we bailing out Wall Street and not our nation’s public schools and colleges? Partly because the crisis in financial capital is immediate while our human capital crisis is unfolding gradually. But maybe it’s also because we don’t have a central banker for America’s human capital – someone who warns us as loudly as Ben Bernanke did a few months ago when he was talking about Wall Street’s meltdown, of the dire consequences that will follow if we don’t come up with the dough.

Dire consequences, indeed.

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Science Stimulus

03.10.09 by Daniel Gaddy

On February 13th, the United States Congress passed an economic stimulus bill that provides significant improvement to federal science funding, and President Obama signed the bill into law on February 17th. Below are two newsletters that have been forwarded to many of us in the science community. These reports provide details about the package and its impact on science funding. The first report is from the US Congress, outlining where the $787 billion will be spent. The second report is from Howard Garrison, the Director of Public Affairs at the Federation of American Societies for Experimental Biology, and specifically deals with the funds allocated to the NIH.

 

United States Congress

The American Recovery and Reinvestment Act of 2009
Creating Jobs, Supporting the States and Investing in Our Country’s Future

The United States is facing its deepest economic crisis since the Great Depression, one that calls for swift, bold action. The goals of this legislation are the same as they have been from day one: to strengthen the economy now and invest in our country’s future.

This legislation will create and save jobs; help state and local governments with their budget shortfalls to prevent deep cuts in basic services such as health, education, and law enforcement; cut taxes for working families and invest in the long-term health of our economy. We do all of this with unprecedented accountability, oversight and transparency so the American people know their money is being invested responsibly.

To accomplish these goals, The American Recovery and Reinvestment Act provides $311 billion in appropriations, including the following critical investments:

  • Investments in Infrastructure and Science – $120 billion
  • Investments in Health – $14.2 billion
  • Investments in Education and Training – $105.9 billion
  • Investments in Energy, including over $30 billion in infrastructure – $37.5 billion
  • Helping Americans Hit Hardest by the Economic Crisis – $24.3 billion
  • Law Enforcement, Oversight, Other Programs – $7.8 billion


Investments in Infrastructure and Science include:

Infrastructure Improvements
- $7.2 billion for Broadband to increase broadband access and usage in unserved and underserved areas of the Nation, which will better position the U.S. for economic growth, innovation, and job creation.
- $2.75 billion for the Department of Homeland Security to secure the homeland and promote economic activity, including $1 billion for airport baggage and checkpoint security, $430 million for construction of border points of entry, $210 million for construction of fire stations, $300 million for port, transit, and rail security, $280 million for border security technology and communication, and $240 million for the Coast Guard.
- $4.6 billion in funding for the Corps of Engineers.
- $1.2 billion for VA hospital and medical facility construction and improvements, long-term care facilities for veterans, and improvements at VA national cemeteries.
- $3.1 billion for repair, restoration and improvement of public facilities at on public and tribal
lands.
- $4.2 billion for Facilities Sustainment, Restoration and Modernization to be used to invest in
energy efficiency projects and to improve the repair and modernization of Department of Defense facilities to include Defense Health facilities.
- $2.33 billion for Department of Defense Facilities including quality of life and family-friendly
military improvement projects such as family housing, hospitals, and child care centers.
- $2.25 billion through HOME and the Low Income Housing Tax Credit program to fill
financing gaps caused by the credit freeze and get stalled housing development projects
moving.
- $1 billion for the Community Development Block Grant program for community and economic
development projects including housing and services for those hit hard by tough economic times.
- $1 billion for the Bureau of Reclamation to provide clean, reliable drinking water to rural areas
and to ensure adequate water supply to western localities impacted by drought.

Transportation
- $27.5 billion is included for highway investments
- $8.4 billion for investments in public transportation.
- $1.5 billion for competitive grants to state and local governments for transportation
investments.
- $1.3 billion for investments in our air transportation system.
- $9.3 billion for investments in rail transportation, including Amtrak, High Speed and Intercity
Rail.

Public Housing
- $4 billion to the public housing capital fund to enable local public housing agencies to address a $32 billion backlog in capital needs — especially those improving energy efficiency in aging buildings.
- $2 billion for full-year payments to owners receiving Section 8 project-based rental assistance.
- $2 billion for the redevelopment of abandoned and foreclosed homes.
- $1.5 billion for homeless prevention activities, which will be sent out to states, cities and local
governments through the emergency shelter grant formula.
- $250 million is included for energy retrofitting and green investments in HUD-assisted housing projects.

Environmental Clean-Up/Clean Water
- $6 billion is directed towards environmental cleanup of former weapon production and energy
research sites.
- $6 billion for local clean and drinking water infrastructure improvements.
- $1.2 billion for EPA’s nationwide environmental cleanup programs, including Superfund.
- $1.38 billion to support $3.8 billion in loans and grants for needed water and waste disposal
facilities in rural areas.

Science
- $1 billion total for NASA.
- $3 billion total for National Science Foundation (NSF).
- $2 billion total for Science at the Department of Energy including $400 million for the
Advanced Research Projects Agency—Energy (ARPA-E).
- $830 million total for the National Oceanic and Atmospheric Association (NOAA).

Investments in Health include:

- $19 billion, including $2 billion in discretionary funds and $17 billion for investments and
incentives through Medicare and Medicaid to ensure widespread adoption and use of
interoperable health information technology (IT).  This provision will grow jobs in the
information technology sector, and will jumpstart efforts to increase the use of health IT in doctors’ offices, hospitals and other medical facilities.  This will reduce health care costs and improve the quality of health care for all Americans.
- $1 billion for prevention and wellness programs to fight preventable diseases and conditions with evidence-based strategies.
- $10 billion to conduct biomedical research in areas such as cancer, Alzheimer’s, heart disease and stem cells, and to improve NIH facilities.
- $1.1 billion to the Agency for Healthcare Research and Quality, NIH and the HHS Office of
the Secretary to evaluate the relative effectiveness of different health care services and treatment options.

Investments in Education and Training include:

- $53.6 billion for the State Fiscal Stabilization Fund, including $39.5 billion to local school
districts using existing funding formulas, which can be used for preventing cutbacks, preventing layoffs, school modernization, or other purposes; $5 billion to states as bonus grants for meeting key performance measures in education; and $8.8 billion to states for high priority needs such as public safety and other critical services, which may include education and for modernization, renovation and repairs of public school facilities and institutions of higher education facilities.
- $13 billion for Title 1 to help close the achievement gap and enable disadvantaged students to reach their potential.
- $12.2 billion for Special Education/IDEA to improve educational outcomes for disabled children. This level of funding will increase the Federal share of special education services to its highest level ever.
- $15.6 billion to increase the maximum Pell Grant by $500.  This aid will help 7 million students pursue postsecondary education.
- $3.95 billion for job training including State formula grants for adult, dislocated worker, and youth programs (including $1.2 billion to create up to one million summer jobs for youth).

Investments in Energy include:

- $4.5 billion for repair of federal buildings to increase energy efficiency using green technology.
- $3.4 billion for Fossil Energy research and development.
- $11 billion for smart-grid related activities, including work to modernize the electric grid.
- $6.3 billion for Energy Efficiency and Conservation Grants.
- $5 billion for the Weatherization Assistance Program.
- $2.5 billion for energy efficiency and renewable energy research.
- $2 billion in grant funding for the manufacturing of advanced batteries systems and
components and vehicle batteries that are produced in the United States.
- $6 billion for new loan guarantees aimed at standard renewable projects such as wind or solar
projects and for electricity transmission projects.
- $1 billion for other energy efficiency programs including alternative fuel trucks and buses,
transportation charging infrastructure, and smart and energy efficient appliances.

Help for Workers and Families Hardest Hit by the Economic Crisis includes:

- $19.9 billion for additional Supplemental Nutrition Assistance Program (SNAP), formerly Food
Stamps, to increase the benefit by 13.6 percent.
- Child Care Development Block Grant: $2 billion to provide quality child care services for an
additional 300,000 children in low-income families who increasingly are unable to afford the high cost of day care.
- Head Start & Early Head Start:  $2.1 billion to allow an additional 124,000 children to participate in this program, which provides development, educational, health, nutritional, social and other activities that prepare children to succeed in school.
- State and Local Law Enforcement:  $4 billion total to support law enforcement efforts.
- $555 million to expand the Department of Defense Homeowners Assistance Program (HAP)
during the national mortgage crisis.

Unprecedented Oversight, Accountability and Transparency

The American Recovery and Reinvestment Plan provides unprecedented oversight, accountability, and transparency to ensure that taxpayer dollars are invested effectively, efficiently, and as quickly as possible.

- Funds are distributed whenever possible through existing formulas and programs that have proven track records and accountability measures already in place.
- Numerous provisions in the bill provide for expedited but effective obligation of funds so that
dollars are invested in the economy as quickly as possible.
- The Government Accountability Office and the Inspectors General are provided additional funding for auditing and investigating recovery spending.
- A new Recovery Act Accountability and Transparency Board will coordinate and conduct oversight of recovery spending and provide early warning of problems.
- A special website will provide transparency by posting information about recovery spending,
including grants, contracts, and all oversight activities.
- State and local whistleblowers who report fraud and abuse are protected.
- There are no earmarks in this bill.

 

The full text of the bill can be found here.

From FASEB:

” I have just finished speaking with Raynard Kington, Acting Director of the NIH, and he has given me the basic outline of how NIH will allocate the new funding from the stimulus bill:

As we know, the legislation provided a total of $10.4 billion.  Of this sum, 1.3 billion will go to NCRR [National Center for Research Resources] ($1 billion for competitive extramural facilities; $300 million for shared instrumentation).  Another $500 million goes to intramural facilities and $400 million gets transferred to the Agency for Healthcare Research and Quality.

A total of $8.2 billion goes to the NIH Office of the Director [OD], of which $7.4 billion is transferred to the I/Cs [Institutes/Centers] with $800 million remaining in OD for trans-NIH initiatives.

Here is the basic outline of how the $8.2 billion will be spent. There will be three major mechanisms with the bulk of the funding going to mechanisms 1 and 2:

1.  R01 applications already in the funding queue Two years of funding will be provided for those applications that can benefit from two years of funding and align with I/C priorities.  A few applications may get four years of funding

2.  Administrative Supplements to existing grants Existing grants with at least one year to run may be given the opportunity or asked to submit supplements that further the goals of the I/Cs.  These will be handled at least in part by requests from the I/Cs and likely with some calls for proposals and could involve equipment, extended funds for postdocs who were not able to move to their own position, summer students, related projects, etc.  There may be other priority issues that the I/C staff want to see funded.

3.  Challenge Grants
A new RFA [Request For Applications] will be released within a week or two for a new, two-year program of cross-cutting, highly innovative projects, $1 M total per project.

Mechanisms for the $400 M for AHRQ [Agency for Healthcare Research Quality] are not yet finalized.

>From what I have learned, this is excellent news.  More information will be available shortly.”

Sincerely,

Dick

~~~
Howard H. Garrison, Ph.D.
Deputy Executive Director for Policy and Director, Office of Public Affairs Federation of American Societies for Experimental Biology 9650 Rockville Pike Bethesda, MD  20814

 

A lot of this may be incomprehensible to the layperson, but what it basically means is a lot more money has been made available for science funding via the NIH, as well as other agencies. The basic mechanisms of the NIH funding are to provide additional money to existing, qualified grants, and to begin funding many new, short-term grants (RFAs). This could go a long way toward stimulating the sciences, as well as the economy as a whole. Much of this money will go toward infrastructure, meaning the construction of new research buildings and laboratories, which provides jobs to the construction industry. When the new labs are constructed, institutions will need to hire new faculty, new Postdocs, new students, and new technicians. This is very good news for those of us in the science community, who have felt a significant crunch over the past several years. Nonetheless, it cannot be overstated that this is a short-term fix – a bandage to stop the bleeding, so to speak. Long-term solutions to science funding will depend upon multiple avenues of support, not solely federal funding. This will also require a fundamental change in our values – as a nation, it is time that we, once again, begin understanding and advocating the importance of science and science education.

The complete list of NIH challenge grants resulting from the American Recovery and Reinvestment Act of 2009 can be found here.

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Gene Therapy for Type-1 Diabetes

02.11.09 by Daniel Gaddy

Introduction.

Type-1 diabetes is a chronic disease resulting from autoimmune-mediated destruction of insulin-producing pancreatic beta cells. Although progress has been made toward improving diabetes-associated pathologies and the quality of life for those living with diabetes, no therapy has been effective at eliminating disease manifestations or reversing disease progression. Therefore, novel therapeutic approaches are currently being sought. Among the approaches with the most promise is gene therapy.

Background on the Disease.

Type-1 diabetes (T1D), also known as insulin-dependent diabetes mellitus, is recognized as a rapidly growing health threat worldwide. The CDC estimates that 15,000 young people in the United States per year are diagnosed with T1D, with 19 new cases per 100,000 youth each year

Existing Therapies.

T1D patients require lifelong insulin replacement therapy, and are at risk of developing significant complications associated with hyperglycemia, such as retinopathy, neuropathy, nephropathy, and accelerated peripheral vascular and coronary artery disease. The goal of existing therapy is to provide tight glycemic control in all diabetic patients in order to minimize the complications associated with hyperglycemia.

Furthermore, while allogeneic islet transplantation has shown some evidence of success, the allo- and autoimmune response against the islets often leads to their destruction

Overview of Preclinical Gene Therapy Studies.

Until recently, gene therapy studies for T1D had focused primarily on ex vivo approaches to modify islets for transplantation. Although many different approaches have been examined, the goals of these modifications are similar: to transfer a gene encoding a protein which would confer some type of islet-protective effect to the grafted islets in order to protect them from allo- and autoimmune attack when transplanted into the patient. When successful, this prolongs graft survival and may potentially reduce the need for systematic immunosuppressive therapy to prevent loss of the graft. Some lingering concerns with the use of transduced islets are safety and efficacy. Particular concerns include whether expression of virally-encoded proteins from the islets will have some effect on the cellular function of the transplanted cells or immunological function of the patient receiving the graft.

Another major focus of ex vivo gene therapy strategies for T1D has been in the modification of immunological cells to promote tolerance upon adoptive transfer in vivo. Dendritic cells have been of particular interest for applications in T1D because of their unique role in regulating T cell responses. Both adenoviral and lentiviral gene transfer of IL-4 to DC have been shown to have protective effects in the NOD model of T1D

Overview of Clinical Gene Therapy Studies.

To date, few proposed gene therapy strategies for T1D have progressed to the point of clinical trials. A Phase I clinical trial to examine safety is currently ongoing using DC genetically modified using antisense oligonucleotides (AS-ODN) to the costimulatory molecules CD40, CD80, and CD86. In preclinical studies using the NOD mouse model of T1D, investigators demonstrated that the AS-ODN treated bone-marrow derived DC were able to delay the incidence of diabetes after a single injection, and observed that the AS-ODN treated DC resulted in an expansion of a CD4+CD25+CD62L+ regulatory T cell population

Conclusions.

Considerable progress has been made towards developing gene therapy approaches for T1D, leading to the development of some phase I clinical trials. Because this disease does not respond well to present biologics, the development of alternative approaches, such as gene therapy, seems highly appropriate. Overall the technology of gene transfer, along with efficacy of gene therapy in animal models of autoimmune diseases, such as T1D, has developed to the point where it is no longer the rate limiting step for many purposes. Instead, the focus of the field of gene therapy for autoimmune diseases is now on bringing these approaches into the clinic.

References.

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Economy and Madoff Scheme Affect Science Funding

01.23.09 by Daniel Gaddy

By now, everyone should be aware of the Bernard Madoff ponzi scheme, which swindled $50 billion from investors. What you may not be aware of is the impact of this scandal on science. Multiple private foundations that fund research have announced that they were victims of Madoff’s scheme. These organization include the Carl and Ruth Shapiro Family Foundation, the Picower Foundation, and the Wunderkind Foundation, and potentially others that have not publicly announced they are victims. When we combine the funds lost as a result of the Madoff scheme with the effects of the current economic downturn, which has cost some private foundations up to 30-40% of their assets, we begin to paint a frightening picture of private research funding. Many of these organizations have announced that they will not be able to fund new research projects in the coming fiscal year, while others have ceased all grant-making, including the payment of grants that have already been awarded, for at least the coming fiscal year.

The effects of this are already being felt at research institutions around the country, including right here in Pittsburgh. Timothy Greenamyre, a Parkinson’s Disease researcher at the University of Pittsburgh, has announced that he lost a $750,000/year grant from the Picower Foundation, which will be closing its doors altogether in the next few months. Furthermore, my own boss has announced that he will not receive renewals of previously-awarded grants from both the Juvenile Diabetes Research Foundation and the Cystic Fibrosis Foundation, two organizations that have suffered losses due to the poor economy.

If you have read this blog before, you know that most funding for biomedical research is awarded through the National Institutes of Health (NIH). You should also be aware that the funding levels of the NIH are among all-time lows as the budget of the NIH has effectively been dropping for the past 8 years. Unfortunately, with the inability of private foundations to fund new awards, and in some cases not even being able to honor their previous obligations, more and more researchers are going to turn to the NIH, and the percentage of funded grants will undoubtedly drop even further over the next year. As a result, many outstanding research projects will not be funded, and many academic scientists may even lose their labs if they are not able to replace lost funding.

We all suffer from this. Scientific advancement requires money, and lots of it. Without science funding, diseases remain uncured and unchecked, healthcare practices and techniques are unimproved, and our overall technological advancement is inhibited. While no one can accurately predict what the coming year holds, we can say that, right now, the foreseeable future of science funding looks grim.

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Cut your energy consumption to save your environment, and your money

01.14.09 by Daniel Gaddy

I was recently made aware of a free online service called WattzOn. WattzOn allows users to measure personal energy consumption, compare consumption over time and with other users, and analyze data that may allow users to cut back on energy consumption, thereby saving money, and potentially the environment.

The United States is the world’s largest energy consumer in terms of total usage, and is seventh in the world in per-capita consumption. Moreover, our energy usage is dramatically outpacing our population growth, suggesting that each one of us is using far more energy than we should be. Furthermore, our energy consumption is only expected to increase over the coming years. With this in mind, those of us who are environmentally-conscious should do everything in our power to cut back on our consumption.

WattzOn is an example of a free service that may allow us to begin doing this. If enough of us make small changes to our lifestyles, large results can be obtained. If doing a small part to save the environment is not enough to motivate you to monitor and alter your energy consumption, perhaps the current economic downturn will provide some additional motivation to cut back on usage and save some money each month.

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Gene Therapy for Rheumatoid Arthritis

11.14.08 by Daniel Gaddy

Introduction.
Gene therapy offers great possibilities for the treatment rheumatoid arthritis (RA). RA was the first orthopedic condition to be targeted by gene therapy. Initially, RA, a non-lethal disease that is not regulated by a single gene, may not have been an obvious target for gene therapy. However, while traditional surgical and pharmaceutical methods of treating RA have met with limited therapeutic success and have failed to produce a cure, the past several years have seen extensive progress toward development of gene therapy for arthritis. Numerous vectors and therapeutic genes have been investigated in animal models of arthritis, and the potential of gene therapy to treat or manage RA has been demonstrated in several clinical studies. Gene therapy offers the possibility of overcoming many of the limitations of current biologic therapies by providing long-term, high-level localized expression of therapeutic genes, potentially in as little as a single dose.

Gene therapy emerged as a novel strategy to treat arthritis in the early 1990s. Fundamentally, arthritis gene therapy involves the transfer of complementary DNA (cDNA) encoding antiarthritis gene products, which may be difficult to administer by more conventional methods. Gene therapy offers the promise of long-term expression of antiarthritis gene products, as well as targeted delivery to and expression in affected tissues, limiting potential systemic side effects.

Background on the Disease.
Arthritis is the leading cause of disability among adults in the United States, affecting approximately 21% (more than 46 million) adults. Rheumatoid arthritis (RA) affects approximately 1.3 million adults in the United States, and more than 60 million people worldwide [1]. RA is characterized by inflammation of the synovial lining and destruction of extraarticular bone and cartilage [2]. It is believed that arthritogenic peptides, either from foreign or self proteins, are presented to T cells preferentially by RA-associated MHC molecules on antigen-presenting cells [3]. Activated T cells produce a variety of proinflammatory cytokines, including TNF?, IL-1 and IL-6. The inflammatory response induced by these cytokines is directly responsible for the overt RA symptoms, including joint pain, swelling, effusion and stiffness.

Existing Therapies.
Despite the prevalence and rising economic burden of RA, effective therapies for this disease remain limited, and there is no cure. Current therapies consist of early, aggressive and continuous treatment with non-steroidal anti-inflammatory drugs (NSAIDs) and disease-modifying antirheumatic drugs (DMARDs). Among the DMARDs, methotrexate has long been the drug of choice for RA, but newer biologic targeted therapies have emerged in recent years. These targeted therapies include Orencia®, a fusion protein composed of the extracellular domain of cytotoxic T lymphocyte antigen-4 fused to an immunoglobulin (CTLA4-Ig); Kineret®, an interleukin-1 receptor antagonist (IL-1Ra); Remicade®, a chimeric anti–TNF? antibody; Humira®, a fully human anti–TNF? antibody; and Enbrel®, a soluble TNF? receptor [4]. As a result of these therapies, the outlook for RA patients is better than at any time in our history. However, it is important to remember that these drugs provide treatment, not cures. In addition, the chronic nature of the disease necessitates lifelong treatment for most patients. Therefore, the long-term efficacy, safety and expense of these drugs remain concerns, particularly due to the high systemic doses and repeated intravenous or subcutaneous administrations necessary to achieve therapeutic results.

Overview of Preclinical Gene Therapy Studies.
Given the success of biologic targeted therapies, various strategies have been employed to utilize these immunomodulatory agents in RA gene therapy. Multiple preclinical RA gene therapy studies have demonstrated that gene therapy vectors, including retrovirus and adenovirus vectors, expressing IL-1Ra produce high levels of the transgene in target tissues and inhibit inflammation and cartilage loss in animal models. Similarly, numerous studies have demonstrated the effectiveness of blocking TNF? activity via gene therapy, including the suppression of inflammatory cell infiltration, pannus formation, cartilage and bone destruction, and expression of joint proinflammatory cytokines in animal models [4].

Furthermore, AAV expressing a TNFR:Fc fusion gene under the control of an inflammation-inducible NF-?B promoter delayed disease onset and decreased the incidence and severity of joint damage in mouse and rat arthritis models [4]. This type of gene therapy, utilizing a disease-inducible promoter, is of particular interest in autoimmune diseases like RA, which are characterized by flare-ups followed by periods of disease regression. By utilizing the inflammation-inducible NF-?B promoter, high levels of transgene expression are obtained only during disease flares, preventing unnecessary exposure of the patient to immunosuppressive agents during periods of disease regression.

In addition to proinflammatory cytokines, an important role for NF-?B signaling has been established in RA. NF-?B controls the expression of proinflammatory mediators of RA, including TNF?, thus may serve as a master regulator of the disease. In terms of gene therapy, both adenovirus and AAV have been utilized to deliver NF-?B inhibitors to synovium, successfully preventing expression of proinflammatory cytokines [5, 6].

A variety of growth factors have also been studied as therapeutics for RA. Bone morphogenetic proteins (BMPs), particularly BMP-2 and BMP-7, have been shown to induce chondrogenesis and osteogenesis when delivered by adenovirus or AAV vectors [4]. Additional growth factors that have been studied in relation to RA gene therapy include transforming growth factor (TGF)-?1 and insulin-like growth factor (IGF)-1. Adenovirus or AAV vectors expressing TGF-?1 have been used to transduce mesenchymal stem cells (MSCs) and drive ex vivo differentiation of MSCs into chondrocytes, facilitating cartilage repair in animal models [7]. Similarly, ex vivo chondrocytes transduced with an adenovirus expressing IGF-1 enhanced matrix synthesis and cartilage repair in horses [8]. These studies suggest important roles for growth factors in RA gene therapy, and indicate that a variety of growth factors may be able to join the list of effective RA therapies.

Overview of Clinical Gene Therapy Studies.
Early arthritis gene transfer trials used retrovirus vectors in ex vivo protocols to deliver IL-1Ra to the metacarpophalangeal joints of RA patients [9]. These safety and feasibility studies illustrated that gene transfer to RA joints could be safe and effective, but the low numbers of patients enrolled prevented any conclusions with regard to efficacy. A similar Phase I trial has been initiated by TissueGene, Inc utilizing retroviral vectors to transduce human chondrocytes, which are then mixed with normal human chondrocytes and injected into the knee of patients with degenerative joint disease. Currently, 16 patients have been treated in the United States and South Korea, with approximately 50% of the treated patients demonstrating symptomatic improvement [4, 10].

Another ongoing RA gene therapy trial is sponsored by Targeted Genetics, Inc and is evaluating the safety and efficacy of a single-stranded rAAV2 virus expressing the complete coding sequence of a TNFR:Fc fusion protein, which is identical to Enbrel®. This trial received much publicity in 2007 because of the death of an enrolled patient. Subsequent investigation determined that the death of the subject was not likely due to the virus vector [4]. Despite the death of this subject, the Targeted Genetics trial has shown promising results. The AAV vector appears safe, in that there is no evidence of circulating TNFR:Fc or extraarticular over-expression of TNFR-Fc, which would have indicated vector dissemination and amplification in extraarticular tissues. Clinical response was assessed using patient reported outcomes, revealing moderate improvement in target joint pain and swelling [11].

Conclusions.
Over the past several years, significant advancement has been made in the field of arthritis gene therapy. Numerous vectors and therapeutic genes have been tested and shown to have varying degrees of efficacy. However, while more than 1000 gene therapy clinical trials have been conducted or are ongoing, at least 32 of which have entered Phase III, only a limited number of these trials have been in the field of arthritis. Those trials that have attempted to combat arthritis have shown significant promise, while also serving as reminders that more work is needed. Future clinical trials are already being designed that will incorporate lessons learned from earlier trials, helping the field continue to move forward. With the recent Chinese approval of Gendicin [12], the world’s first commercially available gene therapy, for head and neck cancers, the field of gene therapy seems poised to finally realize its long-standing potential. The hope remains that gene therapy will soon join the arsenal against RA and other orthopedic diseases.

References.
1.    Lundkvist J., Kastäng F., and Kobelt G. (2008). The burden of rheumatoid arthritis and access to treatment: health burden and costs. The European Journal of Health Economics. 8, S49-S60.
2.    Smolen J., and Aletaha D. (2008). The burden of rheumatoid arthritis and access to treatment: a medical overview. The European Journal of Health Economics. 8, S39-S47.
3.    Gregersen P.K., Silver J., and Winchester R.J. (1987). The shared epitope hypothesis. An approach to understanding the molecular genetics of susceptibility to rheumatoid arthritis. Arthritis Rheum. 30, 1205-1213.
4.    Gaddy D.F., and Robbins P.D. (2008). Current status of gene therapy for rheumatoid arthritis. Current Rheumatology Reports. 10, 398-404.
5.    Amos N., Lauder S., Evans A., Feldmann M., and Bondeson J. (2006). Adenoviral gene transfer into osteoarthritis synovial cells using the endogenous inhibitor IkappaBalpha reveals that most, but not all, inflammatory and destructive mediators are NFkappaB dependent. Rheumatology (Oxford, England). 45, 1201-1209.
6.    Tas S.W., Adriaansen J., Hajji N., Bakker A.C., Firestein G.S., Vervoordeldonk M.J., and Tak P.P. (2006). Amelioration of arthritis by intraarticular dominant negative Ikk beta gene therapy using adeno-associated virus type 5. Human gene therapy. 17, 821-832.
7.    Pagnotto M.R., Wang Z., Karpie J.C., Ferretti M., Xiao X., and Chu C.R. (2007). Adeno-associated viral gene transfer of transforming growth factor-beta1 to human mesenchymal stem cells improves cartilage repair. Gene therapy. 14, 804-813.
8.    Goodrich L.R., Hidaka C., Robbins P.D., Evans C.H., and Nixon A.J. (2007). Genetic modification of chondrocytes with insulin-like growth factor-1 enhances cartilage healing in an equine model. 89:672-685. J Bone Joint Surg Br. 89, 672-685.
9.    Evans C.H., Robbins P.D., Ghivizzani S.C., Herndon J.H., Kang R., Bahnson A.B., Barranger J.A., Elders E.M., Gay S., Tomaino M.M. et al. (1996). Clinical trial to assess the safety, feasibility, and efficacy of transferring a potentially anti-arthritic cytokine gene to human joints with rheumatoid arthritis. Human gene therapy. 7, 1261-1280.
10.    Lee K.H. (2008). Preclincal and early clinical analysis of allogeneic chondrocytes transfected retrovirally with TGF-beta1 gene for degenerative arthritis patients. 5th International Meeting of Gene Therapy of Arthritis and Related Disorders.
11.    Mease P., Wei N., Fudman E., Kivitz A., Schechtman J., Trapp R., Hobbs K., Anklesaria P., and Heald A. (2008). Safety, Local Tolerability and Clinical Response After Intra-articular Administration of a Recombinand Adeno-associated Vector Containing a TNF Antagonist in Inflammatory Arthritis. EULAR Congress 2008.
12.    Wilson J.M. (2005). Gendicine: the first commercial gene therapy product. Human gene therapy. 16, 1014-1015.

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