Tag Archives: 3Rs

Good Lord! They’re Defending Animal Research

Posted on October 27, 2011 by | 7 Comments

Individual European governments are currently working out how to translate a new EU Directive on Animal Research into their own national laws. It would seem a good time for governments to be talking about the benefits of well-funded, humane research using animals. Wait a minute …. the British Parliament are.

To ask Her Majesty’s Government what plans they have to change the regulations governing experiments on animals.

On the 24th October 2011 the British House of Lords (Upper House of Parliament) debated the issue of animal research regulation (click for full text of debate). In response to Lord Wills’ initial questions on the impact of the directive on UK law there was a flood of support for the medical breakthroughs made possible by animal research.

The House of Lords

Lord Winston

Lord (Professor) Winston, an eminent British scientist who works in both reproductive biology and the field of organ transplantation, spoke of the role of animals in experiments in his own field.

My field has largely been that of in vitro fertilisation and reproductive biology. It is interesting to consider that more than 1 million babies could not have existed without the research that has been carried out on rodents. That is true of my work in the screening of embryos for genetic disorders. This has been a revolution in reproductive medicine. It means that women can embark on a pregnancy knowing for certain that they will be free from having a baby which will die in the first few years of life. That was made possible purely through extensive animal research. Animal research has contributed hugely to physiological medical research in virtually every field, whether it be the liver, heart, brain or kidneys, or neuroscience or any major discipline.

Lord Winston also spoke of the need for the Government, and scientific community to engage the public on this issue.

It is quite shocking that every university in this country does not admit that we have an animal house where we do animal experiments. If we do not say this very clearly to the public, if we do not make that message clear, then of course people will start to think there is something clandestine or something to be ashamed of in our research programmes. I really do not think that is true

Baroness Warwick of Undercliffe

Baroness Warwick of Undercliffe, spoke clearly about the benefit of animal research and the high standards of care that exist in the UK.

From my previous experience in the university world, where a substantial proportion of medical research is conducted, I know that the highest standards of ethical behaviour are required and adhered to. That is as true in research involving animals as in other areas. Research using animals has been the fundamental basis for many of the medical advances that we now rely on. I do not think that I can do better than quote the Wellcome Trust, one of the most important funding charities in this field. It said:

“The use of animals in research has enabled major advances in the understanding of biology and led to the development of nearly every type of drug, treatment or surgical procedure in contemporary medical and veterinary practice”.

There is a long list of diseases and treatments where these advances have had an impact-tuberculosis, Parkinson’s disease, high blood pressure, stroke, asthma, Alzheimer’s, and anaesthetics. In the area of organ transplants, in which I have an interest as chair of the Human Tissue Authority, heart and kidney transplant techniques, together with vital anti-rejection medication, were developed using animals-as my noble friend Lord Winston described so vividly. In the financial year 2009-10, 3,706 people received major organ transplants through the NHS.

Using sentient animals in research places a huge responsibility on researchers and Governments. Regulation is therefore essential. Indeed, the UK was the first country in the world to protect research animals by law, in 1876. The UK is now widely regarded as having the tightest legislative control on medical research in the world, together with a reputation for high animal welfare standards. Perhaps even more telling, in order to obtain a license to experiment on animals, researchers must demonstrate to the Home Office that their research cannot be done using alternative non-animal methods.

Lord Taverne, founder of Sense about Science, spoke about the importance of
public support.

Public support is of course important-as many previous speakers have pointed out. The progress made in the three Rs also plays a part in this, and there is no doubt that there has been better education, but it could still be improved. I would add to the suggestion of the noble Lord, Lord Winston, that it would be beneficial if every general practice surgery displayed a notice stating, “All the drugs used or recommended in this surgery have been tested on animals”.

[...]

It is for the sake not only of the health of human beings but of the welfare of animals that we continue to be vigilant to ensure that animal research proceeds effectively and with due care for the animals affected.

Lord Willis of Knaresborough

Lord Willis of Knaresborough, who formerly chaired the House of Commons Science and Technology Committee (as an MP in 2010), gave the Government’s position.

Our priorities are: to promote high-quality science and patient benefits; to ensure high standards of animal welfare; to apply the principles of the three Rs; to harmonise EU regulatory requirements so that we do not have different levels in different countries; and to promote public confidence in humane animal research, which can be done only through openness and transparency. … You cannot achieve world-class research unless you treat your animal models with respect and care.

The British Government continue to affirm their commitment to well regulated biomedical research involving animals. Thank the Lords!

Cheers

Tom Holder

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Embracing the 3Rs

Posted on April 13, 2011 by | 1 Comment

Guest post from Jayne Mackta, President of the New Jersey Association for Biomedical Research, and CEO of Global Research Education & Training, LLC

At NJABR’s recent Strategy Summit entitled Animal Research: Risks & Reality, keynote speaker Jerrold Tannenbaum cautioned the audience to be aware of shifts in language that have tremendous power to affect public perceptions and ultimately public policy. His focus on enrichment took me by surprise and got me thinking. He pointed out that when Russell and Burch introduced their now famous 3Rs in 1959, the principles of Replacement, Reduction and Refinement were strategies for minimizing pain and/or distress in laboratory animals.

Over the years, the research community has embraced the 3Rs, which are intrinsic to good science methodology. We are always seeking better, faster, more efficient ways to move the process forward, including seeking ways to replace animals, reduce the number of animals used, and refine techniques.

Enrichment is a form of Refinement, which is described in the New Guide as “modifications of husbandry or experimental procedures to enhance animal well-being and minimize or eliminate pain and distress.” Note the expansion of the concept to animal well-being.

Enrichment itself has more to do with the animal’s environment where the emphasis is on promoting species-specific behaviors, which does affect well-being and implies minimizing or eliminating pain and distress. However, the focus on “providing animals with sensory and motor stimulation” and promoting “psychological well-being” represents quite a shift from the original meaning of the 3Rs and certainly ramps up the role of enrichment in the humane care of laboratory animals. As a community, we need to think about what we say we are doing and carefully watch our words. We struggle to equate the 3Rs with the term “alternatives” that is commonly understood to stand for efforts to replace animals. For some, replacement has become an end in itself. I think we must be careful not to let enrichment become just another weapon in the war of words to end animal research.

Regards

Jayne Mackta, Publisher
President & CEO, Global Research Education & Training, LLC (GR8)

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Highlights from Nature’s Q&A

Posted on February 25, 2011 by | Leave a comment

Today (about 5 minutes ago), Nature ran an online Q&A session on the subject of animal research to fit in with its latest special editorial on the topic.

There was a lot of interesting background to the Q&A session in the latest issue including a the results of a poll of around 1,000 scientists. Over 90% of the scientists (70% of whom conduct research) believed that animal research was crucial to the advancement of biomedical science (2.7% disagree, 0.7% strongly disagree):

Nature Poll of 1,000 ResearchersA more interesting result came from the question that asked:

Nature Poll of 1,000 ResearchersIt was interesting to see that the UK, where animal rights activism is at an all-time low, considers it a bigger threat than the US. Perhaps this is because the UK has seen the damage that animal rights activism can do to biomedical research. Also of note was that almost no one in the rest of Europe disagreed with the premise, perhaps reflecting the generally high levels of extremism which have occurred across the continent.

Another background article was Tipu Aziz and John Stein’s (of Pro-Test) piece on the importance of speaking out (we approve!) Their article was next to Ranga Yogeshwar who suggested those conducting animal research should “[s]tay as far away from the camera as possible” (we don’t approve!!) Tipu and John made a clear and forceful argument, and their conclusion is one of the most clear and succinct pieces of reasoning for advocacy:

In this electronic age, remaining silent is not an option for scientists engaged in animal research; anyone can use Google to look up what a researcher does. The sensible thing is to be proactive and prepared to defend our work. The public needs to hear all sides of the story.

Anyhow, on to the Q&A:

The discussion began with questions over the impact of animal rights activism and extremism on the scientists and their research. This was later beautifully summed up by the Nature news writer and discussion moderator, Daniel Cressey:

What we were trying to bring out in the feature is that the fringes are currently defining the debate for a huge proportion of policy makers and scientists. I’d love to get to the point where the minority who are extremists don’t have this power over the debate.

His fellow news writer and discussion moderator, Brendan Maher, commented:

[...] that violent elements are few and far between. But they do so much to derail any fruitful conversation, they must be countered strongly. As soon as you introduce fear or intimidation into the debate, there’s no more room for intelligent conversation.

There were some comments on the impact of Pro-Test in the UK, as well as the benefits of added legal restraints and sanctions to activist actions. In reply to concerns from one scientist about speaking up, Daniel Cressey replied:

I think that the Pro-Test group has shown how support of animal research can be done, and done well and safely. The real danger – to my mind – is keeping silent on this. Scientists should be proud of the work they do, whether or not that involves animals.

In the UK there is the perception that tougher laws have helped. One of our features from this week looks at one activist who fell foul of them (http://www.nature.com/news/2011/110223/full/470454a.html). In the US they have had some teething problems, but they do show that attacks on animal researchers will not be tolerated.

Discussion quickly moved onto the 3Rs, and whether enough was being done to ensure they were being put in place. ToniS said:

We asked our researchers if there were blockers to doing more for the 3Rs. They all said “time.” They are under so many pressures to focus on commercialization. How do we MAKE the time internally or do we “outsource” through academia, consortia, or scholarships?

Science Blogger Harlequinclrty took the time to comment on some of the replies (in 140 characters or less):

And @tomholder nails it: “It is not a case of 3Rs research or normal research—the 3Rs are just principles of good science” #animalresearch

And @tomholder continues to nail it: “just because they are not called the 3Rs does not mean people don’t use them” #animalresearch

At the accusation that the 3Rs was not understood by all scientists, Barbara Davies of Understanding Animal Research said:

Let’s face it, the three Rs are jargon. If we talk about the principles underlying the jargon, most scientists will recognise them.

There were many more insightful comments from the variety of people who contributed, and you can read it all on Nature’s website.

Regards

Tom Holder

 

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How to build a lung

Posted on June 25, 2010 by | 3 Comments

Tissue engineering, a field that combines cell biology, engineering, and materials science to manufacture tissues – and more recently even whole organs – to replace those lost to injury or illness, must be one of the most exciting areas in modern medicine.  Since the earliest reports about a mouse with a human ear growing on its back over a decade ago progress has been rapid, and last year we reported on how animal research enabled scientists to use a patient’s own stem cells to successfully replaced a trachea that suffered irreparable damage from tuberculosis.

Now science writer Ed Yong has written an excellent article on his Not Exactly Rocket Science blog about how a team of scientists at led by Laura Niklason Yale University are moving on from the trachea to a far more complex part of the respiratory system – the lung – and successfully transplanted it into rats.  As Ed points out, this technology needs to be improved significantly before it can be attempted in humans, and further research in rats is underway to do just that.  This work will take time, and as it progresses will almost certainly require studies in larger animals such as pigs whose lungs are closer to ours in size and structure than those of rats. Human trials are not expected for perhaps a decade or more.

Ed Yong was not the only one to note the importance of this research, the journal Science, in which the study was published (1), have included an interview with Laura Niklason in their latest podcast.

How to build a lung. Courtesy of Laura Niklason and Thomas Petersen.

Laura Niklason’s past record certainly gives cause for optimism. In 1999 they published a paper describing how they engineered arteries in vitro that supported blood flow when transplanted into pigs, an animal whose cardiovascular system is a valuable model for our own, and determined that a culture technique that mimics the pulsating arterial blood flow produced stronger and safer engineered arteries. Following a decade of refinement through in vitro tissue culture and animal research the artery is expected to enter human clinical trials next year.

And Laura Niklason’s group is not the only one that is working hard to develop tissue engineered lungs for transplant, at the Harvard University Medical School in Boston Professor Harald Ott and his colleagues have also had promising results with transplanted lab grown lungs in rats.

Engineered rat lungs in a bioreactor at Dr. Harald Ott's lab in Boston. Credit: National Geographic Explorer.

This wasn’t the only exciting lung-related research to be published in Science this week.  Scientists at Harvard University have used microfluidics to re-create the interface between the alveoli and capillaries (2) in the lung where exchange of oxygen and other gasses takes place. The response of this “Lab-on-a-chip” model to bacterial infection and inflammatory signals was similar to that seen in previous animal studies.

This technology represents huge advance over existing in vitro models of the lung; which, in addition to being a very promising research tool in its own right, has the potential to reduce the number of animals used in testing the effect of new drugs or toxins on lung function.  Eventually an improved version, perhaps combined with chips that simulate other tissue types, might replace animal use in the evaluation of toxicity in the lung entirely, though that goal is still years of dedicated research away.  Lab-on-a–chip technologies such as this that can integrate several cell types into a system that mimics real tissues in vivo are a great example of the 3Rs in action.

How to build a lung on a chip. Image courtesy of Huh D. et al. Science Volume 328 (5986), pages 1662 - 166 (2010)

One area the Harvard scientists were particularly interested in is using this lab-on–a-chip to evaluate the potential toxicity of nanoparticles, since existing in-vitro cell and tissue culture technologies are not adequate for this task, and using rodents is slow and expensive. Since nanoparticles are becoming increasingly common in daily life there is an urgent need to develop ways to rapidly assess their safety before humans and animals are exposed to them. So they examined how their lab-on–a-chip responded to a variety of nanoparticles, and then compared the results to those of parallel studies performed on the lungs of mice.

A key question was whether inhaled nanoparticles can cross into the bloodstream, several animal studies indicate that they can while in vitro studies suggest otherwise, though as mentioned the relevance of these in vitro methods has been questioned. With the new technology the results were in close agreement, the nanoparticles can cross into the bloodstream. This demonstration indicates that the lab-on-a-chip may provide a suitable platform for future evaluation of aspects of nanoparticle toxicity, as part of new pathways for the evaluation of chemical safety that use as few animals as possible.

So, all in all it is a very great week for building lungs in Science, one to which animal research made a huge contribution.

Paul Browne

1)      Patersen T.H. et al. “Tissue-Engineered Lungs for in Vivo Implantation”   Science Published Online June 24, 2010 DOI: 10.1126/science.1189345

2)      Huh D. et al. “Reconstituting Organ-Level Lung Functions on a Chip”  Science Volume 328 (5986), pages 1662 – 1668 (2010) DOI: 10.1126/science.1188302

Addendum

In my rush to finish the above post I forgot to mention another advance in the use of decellularized scaffold and in vitro cell repopulation approach to tissue engineering, scientists at Harvard Medical School produced artificial livers that appeared to function almost as well as normal tissue when transplanted into rats and connected to their blood supply . In the research paper published online in Nature Medicine the authors stress that the artificial liver needs further development before human transplants can be contemplated, but this is further evidence of just how quickly progress is being made in the field of complex tissue engineering.

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The Similarity of Human and Animal Models

Posted on February 5, 2010 by | 5 Comments

Most scientists who incorporate animals in their research do so under the strong belief that modern animals (particularly those closest to us in evolutionary terms) exhibit an amazing genetic, physiological and behavioral similarity to Homo sapiens, making them effective model systems in which to understand both humans and animals alike. This is particularly true of monkeys and great apes, and it is the reason that primatologists and physical anthropologists have – for nearly a century – studied these species in the wild and in laboratories. They believe that apes and monkeys are so similar to us that this study can reveal insights into the origins of the human species, to our culture and to our evolutionary history.

This homology is not just contained solely within the primate family, however. Dogs also share a remarkable amount in common with us. This is probably because the human species has spent millenia shaping the genome of the domesticated dog through selective breeding in order to make it an ideal companion who shares our emotional and cognitive lives. Not long ago, it was shown that domesticated dogs have a unique ability to understand the social cues embedded in subtle human behavior, like eye gaze, while many chimpanzees do not. This is probably why we favor them as companions – they seem to understand our thoughts and emotions because they have this ability. Importantly, many patients with Autism Spectrum Disorders have difficulty with understanding the thoughts and feelings of others, impairing their ability to relate socially. This suggests that the study of domesticated dogs may provide a unique opportunity to explain the basis of aspects of autism. We can ask what is it that differentiates dogs from other animals that conferred upon them this ability to understand the minds of others. We can then test whether interventions that work through that mechanism are useful treatments for social problems in autism.

A recent paper by researchers in Boston, published in the journal Molecular Psychiatry, further exposes the potential for bio-behavioral studies in dogs. These scientists noted that a significant number of Dobermans had a tendency to engage in behaviors reminiscent of human Obsessive Compulsive Behavior (OCD; including abnormal self grooming – called trichotillomania – and other repetitive motor movements like pacing and checking). By studying a large family of Dobermans who exhibited these traits, the scientists were able to show that there were genetic causes to the behavior and to provide evidence that mutations on dog chromosome 7 were associated with these symptoms. Upon further analysis of their data, they identified an interesting gene (cadherin 2) which is expressed within the brain and may directly relate to these behaviors. We now have an important set of questions to test: what brain circuits is cadherin 2 expressed in? Does the same gene, which is known to be present in humans, relate to OCD? If so, can we treat the symptoms and lessen the distress of patients with OCD by targeting this gene? The millions of patients with OCD undoubtedly await an answer to these questions. What is more, we now have important information that may help to make the lives of these dogs better through lessening the behavioral problems they have inherited through their genes.

Of additional note, these researchers made this discovery by observing the dogs’ behavior and by obtaining a blood sample, revealing the fact that – as many researchers have long asserted – the descriptions of all biomedical research as “vivisection” is a far cry from the truth. Scientists typically refine their approaches in order to use the least invasive and distressing methods to uncover the facts that are required. This is particularly true when considering complex species with evolved cognitive and emotional abilities – like dogs and monkeys. I personally care for two small dogs, and because of this, I – like other scientists – am exceptionally sensitive to the impact of an experiment on the animals that live in our labs. It is with that in mind that we struggle to carry out our research in as refined a manner as is possible given the scientific question being investigated. Indeed, as I have previously asserted, there are many scientific questions that cannot be answered well if the welfare of the subject is ignored and/or if the animal is exposed to stress that will alter its behavior.

While invasive methods are sometimes required to make progress towards treatments for human disease, at other times they are not. Researchers judiciously choose the method that produces the necessary data with the least impact on the subject, and Institutional Animal Care and Use Committees review the decision of any scientist about the level of invasiveness of his/her study. That not withstanding, studies in non-human animals continue to be foundational for our understanding of ourselves, and discoveries regarding the function of the brain and body in health and disease will continue to be made thanks to animal research.

Regards

David Jentsch

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David Jentsch speaks about his research

Posted on May 25, 2009 by | 23 Comments

As a Professor of Psychology and Psychiatry at UCLA, my students, colleagues around the University and I are engaged in an endeavor to improve the quality of life of individuals who suffer from major mental disorders. As committed as we are to making tangible progress towards improving the prognosis and welfare of people suffering from psychoses or addictions, we also concern ourselves with the quality of life of the animals who are the subjects of research, both because we care, and because the quality of our science requires it. To date, a variety of postings on the Speaking of Research website have addressed methods (including the “3 Rs”) for improving the welfare of animals involved in research; here, I outline the scientific necessity for doing so wherever possible.

Vervet Monkeys
In part, our research focuses on discovering the biological determinants of naturally-occurring differences in brain function and behavior. In humans, these individual differences, whether environmentally or genetically determined, can often index vulnerability for mental disorders.  For example, young people who are more impulsive are more likely to drink, smoke, take illicit drugs and engage in high-risk sexual behavior – as well as to develop complications stemming from those behaviors. We find that, like people, some monkeys will impulsively engage themselves in new and risky situations, while others approach more cautiously and try to keep a low profile.  An overlapping set of genes influence these traits in monkeys and in man. Therefore, the animal model represents a very powerful tool to locate unknown genes that influence human traits, and more importantly, to understand (at the biochemical, genomic and cognitive levels) how those genes act to influence temperament and behavior. Without insights about the basic biological determinants of these traits – something not discoverable in humans at the present time – prevention or treatment strategies of any type are difficult or impossible to create.

Vervey Monkeys 2
With these goals in mind, our research program very much depends upon the ability of our animals to exhibit their natural behavioral repertoire, whilst still being maintained under controlled conditions that allow us to isolate external influences and to perform our studies. Consequently, we maintain our animals in social groups, in open air arenas with access to sunlight, with a wide array of environmental stimuli that promote normal foraging and social behaviors. Many of our social groups include families, and most monkeys are raised by their mothers until puberty.  Early separation would produce an “experimental” effect on behavior that would alter the “natural” expression of their traits. In the case of our studies, the conditions needed for enhancing animal welfare and the conditions needed for scientific discovery are the same, and we – like many other scientists – are dedicated to ensuring that we never impede the welfare of our animals when it is unnecessary or unjustified. Poor animal welfare often implies poor science; we avoid both with unrelenting diligence.

J. David Jentsch, Ph.D.

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No more threats, no more fear, animal research is finally here!

Posted on November 12, 2008 by | Leave a comment

Some news from Pro-Test in the UK.

The Oxford Biomedical Facility is finally complete after five bumpy years. Despite violence, arson, threats, intimidation and harassment, Oxford University has pulled through with its new animal research facility. This lab is setting a new “Gold Standard” in animal welfare, one that will meet and exceed the standards set by the Home Office regulations.

Pro-Test played an important part in the building of the lab, bringing the students, scientists and residents of Oxford together to defend the need for animal research in Oxford. By explaining the benefits clearly and countering propaganda from the animal rights groups, Pro-Test helped bring the British public behind the need for this lifesaving medical research.

The life-saving research that can now go ahead in the lab will include work on cancer, stroke, heart disease, diabetes, HIV, muscular dystrophy, motor neurone disease, epilepsy, Parkinson’s and Alzheimer’s. The lab will be using state of the art equipment to help further the 3Rs – Refinement, Replacement and Reduction.

Here’s what Oxford University has to say about the 3Rs:
“In terms of replacement, the facility has been designed so that in the long-term future the space can be used flexibly, including for non-animal research. In terms of reduction and refinement, the facility will bring expertise onto one site, allowing for best advice. Oxford’s Veterinary Services team, which exists to advise on the welfare and health of Oxford’s research animals, has expertise in the 3Rs and will be in the building with training rooms and other facilities that represent a huge improvement from the space they had before.”

The lab will contain 98% rodents, mainly transgenic mice, with non-human primates accounting for less than 0.5% of the animals in the lab.

“With the support of the students, the scientists and the public, the completion of the Oxford Biomedical Facility is a victory for both science and reason. It is our family, our friends, and ourselves who stand to gain from the lifesaving medical research that has marked Oxford University as a world leader in biomedicine . This lab represents not just better facilities for scientists, but also better welfare conditions for the animals within, showing Oxford University’s commitment to the principles of Refinement, Replacement and Reduction in animal research.” – Pro-Test Spokesman.

Cheers

Tom

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Update of the Guide for the Care and Use of Laboratory Animals

Posted on September 22, 2008 by | 1 Comment

In a continuing effort to improve the conditions for animals in research, the Institute for Laboratory Animal Research (ILAR) has initiated an update to the 1996 version of the Guide for the Care and Use of Laboratory Animals (commonly known as the Guide). The Guide is not only the basis for AAALAC International accreditation, but is also central to the Public Health Service Policy on the Humane Care and Use of Laboratory Animals. The Guide’s recommendations carry the force of law based on the Health Research Extension Act passed by Congress in 1985.

The Guide is intended to assist IACUCs, researchers, and veterinarians in fulfilling their obligation to plan, conduct, and oversee animal experiments in accordance with the highest scientific, humane, and ethical principles. The Guide makes recommendations for humane animal care and use based on published data, scientific principles, expert opinion, and experience with methods and practices proven consistent with high-quality, humane animal care and use. It is an important part in the implementation of the 3Rs.

The update effort intends to reflect new scientific information related to the issues already covered in the Guide, and to add discussion and guidance on new topics of laboratory animal care and use related to state-of-the-art animal research programs. Specifically, the committee will review the scientific literature published since the release of the 1996 Guide and determine whether the information currently in the Guide concurs with current scientific evidence. The committee will also review the literature related to new technologies related to laboratory animal care and use and determine where new guidance is necessary to ensure the best scientific outcomes and optimal animal welfare. Three open forums will be held to discuss changes to be made and solicit public opinion.

Regards

Charles

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