Lisa Willemse

Lisa Willemse is a communications professional with 18 years’ experience working in the technology, child development and health research fields, and is currently a Senior Communications Advisor with the Ontario Institute for Regenerative Medicine. With a background in fine art, communications and journalism, Lisa continues to moonlight as a writer, photographer and editor, contributing to a range of Canadian and US-based publications. In 2014, she was invited alumni-in-residence for the acclaimed Science Communications program at the Banff Centre. Follow her on Twitter and Medium @WillemseLA

A Q&A with Dr. David Allan


Wednesday, April 12, 2017

As a medical director with our Cord Blood Bank and OneMatch programs, a scientist in the Sprott Centre for Stem Cell Research at The Ottawa Hospital and associate professor at the University of Ottawa, Dr. David Allan possesses a wealth of knowledge about clinical practice and research directions in blood- and bone marrow-based cellular therapies. He is also the current recipient of Canadian Blood Services’ Kenneth J. Fyke Award, which supports health services and policy research to promote the development of evidence-based Canadian practices and policies in transfusion, blood stem cell transplantation, and organ and tissue donation and transplantation for the benefit of Canadian patients.

 

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Dr. Allan recently shared his thoughts on the award, the project it will support and what he envisions in Canada’s health care future.

Q. Kenneth J. Fyke had a huge impact over four decades in public health, including the creation of a voluntary blood donor system in Canada. Why is receiving an award named after him important to you?

A. As the founding chair of the Board of Directors at Canadian Blood Services, Dr. Fyke’s vision and leadership remain central to the success of Canadian Blood Services in maintaining the public’s trust in the Canadian blood system. Throughout his distinguished career, he was able to build health care systems through his vision and bringing ideas together.

It is inspiring to pursue our vision of a system that will use umbilical cord blood for new areas of treatment, including regenerative therapy, with the support of a research award that bears his name. Our goal is to bring ideas together to develop policies that will bring Canadians one step further into the stem cell era.

Q. Describe the project that the award money is earmarked for.  

A. Our project will systematically summarize the evidence from clinical studies in support of cell therapy using umbilical cord blood cells for tissue regeneration or repair. We will also implement new technology that allows for continuous updating – so we will have a repository of clinical evidence that is always up-to-date.

In collaboration with Tim Caulfield’s team in health policy research at the University of Alberta, we will also summarize the perspective in the press and lay literature to evaluate the gap between what the evidence shows and where inflated expectations exist in the eyes of the public. This will help us address heightened expectations through public education efforts with our many partners within the Canadian stem cell and transplant community.

Our final goal is to develop a policy paper to ensure responsible use of banked cord blood for proven indications that can be used by blood establishments such as Canadian Blood Services to support the safe and optimal choice of treatments for Canadian patients.

Q. And what do you see this leading towards?

A. The goal is to provide a critical policy framework for cell-based regenerative therapy in Canada that ensures the responsible use of umbilical cord blood for effective treatments. Too often, patients who are desperate for a cure will travel out of country for a “stem cell” treatment that is unproven and suffer problems or complications that actually make them worse off. We want to change this trend and ensure Canadian patients have the tools to access treatments that are proven and to know which ones remain experimental or unproven.

Q. Can you elaborate a bit on “unproven” stem cell treatments, particularly those that use stem cells from blood, bone marrow and cord blood sources?

A. Blood stem cell therapy has become a standard treatment for blood-related disorders such as leukemia, but it remains in its infancy for the treatment of many other diseases. Similarly, while publications of regenerative therapy using umbilical cord blood are increasing quickly, it remains very early and we still do not know when it is helpful or not. We still need many more studies that are larger before we will fully understand which diseases will benefit from these treatments.

Q. You’re based in Ottawa and work for Canadian Blood Services, the Ottawa Hospital and the University of Ottawa. What does an affiliation with these organizations mean in terms of your ability to realize your goals?

A. Regenerative therapy using cells that come from cord blood involves expertise from many fields – biomedical lab research, clinical transplant medicine using blood stem cells, and the regulated biopharmaceutical perspective that exist in blood establishments such as Canadian Blood Services. By working at the interface between these three worlds, it allows me to see the strengths and limitations of each part as it applies to umbilical cord blood therapy.

Q. Over your career, what one thing has changed that has had the biggest impact on health?

A. The molecular and cellular era is arriving as we speak. There is a big shift occurring towards a deeper understanding of disease, more accurate diagnostics, personalized prognoses, and new treatments using molecular and cell-based methods. While this makes modern medicine more “intelligent”, it also makes it very costly and we are struggling more and more with the reality of how to ensure accessibility.

Q. How has this change affected your work with Canadian Blood Services?

A. The drive to develop cellular therapy in Canada has fueled enthusiasm over the past several years to build the public umbilical cord blood bank at Canadian Blood Services. Building a successful bank and having policies in place to expand the use of cord blood into regenerative therapy will make this investment a worthwhile venture for years to come.

Q. If you could make one more advance/change happen today, what would it be and how could this award help realize this?

A. It is a big question – and a big answer. I’d like to implement an improved and iterative learning process into our medical system that allows us to integrate new knowledge more efficiently and bring meaningful progress to the bedside earlier. In short, we are trying to ensure patients have access to the best care possible. This includes knowing when something is helpful and it also includes avoiding treatments that are not helpful.

Decision-making needs to be evidence based whenever possible, yet keeping the evidence up-to-date and in a form that can be used by patients and care providers is challenging. Our project hopes to improve this process for Canadian patients.

 

The Kenneth J. Fyke Award program supports health services and policy research in order to promote the development of evidence-based Canadian practices and policies in blood transfusion, blood stem cell transplantation, and organ and tissue transplantation for the benefit of Canadian patients. The 2016 Kenneth J. Fyke Award will support one project with up to $100,000 for a period of one year.

Next competition: Fall 2018

Read more


Canadian Blood Services – Driving world-class innovation

Through discovery, development and applied research, Canadian Blood Services drives world-class innovation in blood transfusion, cellular therapy and transplantation—bringing clarity and insight to an increasingly complex healthcare future. Our dedicated research team and extended network of partners engage in exploratory and applied research to create new knowledge, inform and enhance best practices, contribute to the development of new services and technologies, and build capacity through training and collaboration.

The opinions reflected in this post are those of the author(s) and do not necessarily reflect the opinions of Canadian Blood Services.

Understanding who is "most wanted" when it comes to stem cell and cord blood donors


Wednesday, May 18, 2016
By Lisa Willemse

There’s nothing better than a success story. A touching reunion between a cancer survivor and their stem cell donor. But more often we hear in the news about the desperate search for a match, a plea from an individual or family who are unable to find a matching stem cell donor within their circle and are in desperate need for someone to step forward.

Often you’ll hear pleas calling members of a specific ethnicity to come forward. You might also notice blanket calls for more young men to step up and join a stem cell registry, such as the recent “Real men” campaign in the UK.

Blood stem cell transplants are used to treat over 80 diseases and disorders, including many cancers and inherited immune system and metabolic disorders.

These specific calls are not due to chance: although the diversity of donors has broadened in Canada, there is still a need for more, particularly among some ethnic groups with low representation (i.e. First Nations, Métis, Inuit and African-American). Ideally, those personal plea stories will become a thing of the past, because a matched donor will be easily found in a stem cell registry or bank.

On that front, Canada is doing a very good job. Dr. David Allan, medical director for Canadian Blood Services’ Cord Blood Bank and OneMatch Stem Cell and Marrow Network, reports that more than 1,000 units of cord blood are now available in the public Cord Blood Bank. It officially launched less than a year ago and just over half the units collected represent ethnicities other than Caucasian. A similar diversity profile exists in the OneMatch registry, where more than 350,000 volunteers have come forward to register as possible donors.

The best match for any patient is quite often a sibling. But for a variety of reasons, it’s not always a sure thing, and when it’s not, an unrelated donor is required. Currently, about 600 transplants using stem cells from an unrelated donor take place in Canada each year. While some come from the Canadian registry, many are found in one of several larger international registries.

 

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But for some patients, the transplant doesn’t happen at all. It’s not that easy to tease out the reasons behind this.

“There are multiple possibilities,” says Dr. Allan. “One is there is no suitable donor available. There are also situations in which the patient became too unwell, or the disease was not controlled adequately.” Any one or a combination could be at play, and the one we have the best chance of controlling is ensuring a matched stem cell transplant is available.

Donors and patients are matched according to the compatibility of inherited genetic markers called human leukocyte antigens (HLA). These antigens are inherited from your parents. Up to 12 antigens are considered important in the matching process. The best transplant outcome happens when a patient and donor’s HLA typing closely match.

When it comes to matching, family matters

They say blood is thicker than water, and when it comes to the properties of stem cells that exist in bone marrow (where blood cells are made), circulating blood and umbilical cord blood, this is certainly true. Attached to the surface of those stem cells (and most other cells in your body) are particular proteins – or markers – that are part of the genetic material handed down from parent to child.

These markers, known as human leukocyte antigens, or HLA for short, play a crucial role in the body’s immune response. Cells with your unique HLA profile are considered safe by your immune system, and those with a foreign HLA will be seen as invasive and therefore attacked by your immune cells. It is this immune function that causes some patients to reject transplanted tissues or organs, a situation that can put their lives at risk.

Over at Dalhousie University, it’s Dr. Robert Liwski’s job as medical director of Canadian Blood Services’ HLA typing laboratory to understand the nuances of HLA, to conduct and probe the latest research in order to ensure the highest degree of safety for the patients in Canada who are candidates for a transplant each year.

There are four main classes of HLA (A, B, C and DR) considered important for stem cell transplant purposes. Each is comprised of a sub-set of molecules (as many as 10,000 different molecules in total) with specific immune function. To give an idea of this level of specificity, one molecule, HLA-B53, has a particular affinity towards identifying malarial pathogens – if you get bitten by a malarial mosquito, you want this molecule in your HLA arsenal.

In order to avoid an immune attack against the transplanted stem cells, reduce complications that extend hospital stays, the patient’s body needs to recognize and tolerate the donor HLA markers as its own. There are eight different markers to consider (you get four, one set of A, B, C and DR from each parent, times two parents) when choosing a stem cell donor. You’ll rarely be more than a 50 per cent match to either parent, but, says Dr. Liwski, “roughly 25-30 per cent of people will have an HLA identical sibling.  The other 70 or so per cent need to either go for an unrelated donor search through registries or consider a cord blood donation.”  

Because the immune cells in cord blood are less mature they are not as potent and can therefore tolerate more of a mismatch. But cord blood as a source of transplantable stem cells presents its own problems, chief among which is the relatively small number of viable stem cells in each unit, meaning two units are often required for a single transplant, which increases demand and cost.

Finding a match is also a “neighbourhood” affair

Because HLA is an inherited component of immune response, it also adopts an evolutionary function.

As Dr. Liwski explains, “HLA molecules appear to have evolved to recognize the signatures of infections that are common in the area where you live. So, for example, among the populations that exist in Asia or Africa or Europe there are certain infections that are prevalent in those regions, and for each population, their HLA molecules have evolved to recognize the particular pathogens.”

Remember that HLA-B53 anti-malarial molecule? Turns out it shows up more frequently among some populations than others.

“B53 is very common in people of African origin, present in more than 15 per cent, but it’s rare in Caucasians at only about 0.3 per cent, so this HLA molecule may have simply evolved to try to defend these populations against a pathogen that is prevalent there,” says Dr. Liwski.

 

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Global differences in disease prevalence and HLA evolution help to explain why it’s easier to find an HLA match within your own ethnic group – and why it’s so important for people of all ethnic backgrounds to be adequately represented in the stem cell registry and cord blood banks.

Young males wanted

HLA matching is thorny enough with its evolutionary and hereditary considerations. But there are biological ones as well: it turns out that young males make excellent candidates for stem cell donation. The reasons for this are quite simple.

First, younger, healthy adults (no matter what their gender) tend to have a more robust supply of stem cells available, which means a single donation of peripheral blood or bone marrow can yield more cells for transplant.

Second, pregnancy can throw a bit of a monkey wrench into the matching process. A woman who has been pregnant has been exposed to HLA that is not hers (the baby carries 50 per cent of the father’s genetic code, including HLA), and her immune system has responded with effector cells and antibodies that she now carries in her blood. This higher sensitivity in a previously pregnant donor increases the likelihood of graft vs host disease, a potentially serious complication where the donor immune cells attack the cells, tissues and organs of the recipient.

 

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“It’s not that females are undesired in any way,” Dr. Allan is quick to point out. “What’s most important is that we have committed donors.”

“When donors register, we really count on their willingness to donate, even if it’s some years in the future. Canada’s standing on the international stage is quite admirable, in terms of commitment, both from the males and especially from the females – females tend to remain very committed for very long periods of time. So the contribution from our female registrants is not insignificant and is highly valued.”

What does the future hold?

Getting to that place where more patients in need of a stem cell transplant can find a matched donor may not be that far away. One of the more promising areas of recent research involves a new protocol that is opening up the possibility for greater numbers of transplants from related donors, thereby reducing the demand on the stem cell registries and public cord blood banks.

Called a haplo-identical transplant, this protocol allows for a 50 per cent HLA match to be used (far below today’s clinical standard), in conjunction with a drug that dampens the immune response. Using this protocol means that a parent or child, or a less-than-perfectly-matched sibling can become a stem cell donor. In the past five years, a much greater number of haplo-identical transplants have taken place, primarily in Europe and the US, and early indications are positive.

But both Dr. Allan and Dr. Liwski cautioned that it’s too early to be overly optimistic, as the long-term outcomes for patients is not yet known, and much research still needs to be done to track patient response based on the condition treated. All of this is currently taking place.

Even with the possibility of haplo-identical transplants relieving a bit of the burden, Dr. Allan doesn’t see it reducing the need for new donors in the OneMatch Stem Cell and Marrow Network registry or the Cord Blood Bank. “Because of shrinking family sizes over the recent decades and also because we’re doing transplants in older individuals who may not have a sibling that is healthy enough – or even alive in some cases – to donate cells, so we’re having to rely more and more on unrelated donors and cord blood donors or alternative sources of cells.”

“We still very much need and appreciate our stem cell donors,” he says.

Find out more about the OneMatch Stem Cell and Marrow Network registry and Canadian Blood Services' Cord Blood Bank

What is a hematopoietic stem cell? Narrated by Dr. Connie Eaves from Stem Cell Network on Vimeo.


Canadian Blood Services – Driving world-class innovation

Through discovery, development and applied research, Canadian Blood Services drives world-class innovation in blood transfusion, cellular therapy and transplantation—bringing clarity and insight to an increasingly complex healthcare future. Our dedicated research team and extended network of partners engage in exploratory and applied research to create new knowledge, inform and enhance best practices, contribute to the development of new services and technologies, and build capacity through training and collaboration.


About the Author

Lisa Willemse is a communications professional with 18 years’ experience working in the technology, child development and health research fields, and is currently a Senior Communications Advisor with the Ontario Institute for Regenerative Medicine. With a background in fine art, communications and journalism, Lisa continues to moonlight as a writer, photographer and editor, contributing to a range of Canadian and US-based publications. In 2014, she was invited alumni-in-residence for the acclaimed Science Communications program at the Banff Centre. Follow her on Twitter and Medium @WillemseLA


The opinions reflected in this post are those of the author and do not necessarily reflect the opinions of Canadian Blood Services nor do they reflect the views of Health Canada or any other funding agency.

 

 

The wonder drug you’ve probably never heard of – yet


Wednesday, February 24, 2016

Wonder drug it may be, but IVIg is a slippery fish. Even after 60 years, little is known about precisely how it works.

An encounter with a scientist

The first thing you notice when you walk into Dr. Don Branch’s office at 67 College Street in Toronto is how small it seems. And colourful, owing to an impressive collection of memorabilia that suggests a full and perhaps eclectic life: show posters, photos of his family and small items such as those one would get from a student or colleague sharing an inside joke. Copious as they are, the richness-of-life souvenirs are nearly crowded out by shelves and stacks of books and what appear to be research papers, some in folders, most not. The stacks disappear into the shadows of Branch’s sparsely lit room. 

It’s almost as mysterious and as awe-inspiring as IVIg, or intravenous immunoglobulin, a plasma product used to treat a range of different conditions – and a topic that elicits an immediate and unequivocal amount of passion from Branch, who views it as one of the marvels of modern medicine. I’m here to find out why.

 

 

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I’ve placed my recording device on a remarkably clear desk. Later, Branch will tell me that Einstein is one of his heroes, but now as I sit down to begin the interview, I briefly ponder Einstein’s quote about the state of one’s surroundings being a reflection of the mind. An empty mind this is not. 

But you need not look at Branch’s office to figure this out. The notion is quickly evident with a glimpse at the range and depth of Branch’s research, which spans about 30 years and includes initial work in stem cells before turning his attention to the blood system, transfusion medicine and phagocytosis, the process by which our immune cells identify and devour foreign particles.

His accolades include a key early discovery in HIV back in the 1990s. He still pursues HIV research and speaks with obvious pride of his achievements in that space, but his enthusiasm edges noticeably upward when we turn to the topic of IVIg.

“IVIg has got a huge track record of safety - though there are some significant side effects that include hemolysis and thrombosis events. But, for the most part, it's a miracle drug.” he said.  

Strong words, to be sure, especially when connected with a therapy that many people have never heard of. First used in 1952 to treat immune deficiency, IVIg is a plasma protein product containing the pooled antibodies of thousands of donors. For patients who receive multiple IVIg treatments per year, it represents a critical boost of immunity to help their body fight infection or forestall the progress of an autoimmune disorder. For others, one dose of IVIg can be an outright cure. 

 

A wonder drug is not without its challenges

Wonder drug it may be, but IVIg is a slippery fish. Even after 60 years, little is known about precisely how it works. Its efficacy varies from person to person, even among those with the same disorder, and can vary from treatment to treatment even in the same patient.

And then there are those rare complications. There are blood clots (thrombosis) to watch for, and, inexplicably, some patients contract IVIg-associated hemolysis, a condition in which the introduced antibodies find a marker on the patient’s red blood cells and attack them, causing the cells to rupture. The easy answer would seem to be that the patient should not receive IVIg therapy, but of course, it’s not that simple.

“If a person has one of these reactions to IVIg, the next time they get IVIg they may not,” explained Branch.“It doesn’t make sense to most people either, why would they have one incident and not a second, even with the same lot? It is a black box in many ways.”

Still, these unknowns are not enough to take IVIg off the list of approved therapies, especially when it is the only viable one for conditions such as common variable immunodeficiency or Kawasaki disease. Nor is the expense of production and the fact that Canadian patients must rely on product being made outside Canada – mostly in the US. 

 

 

An ounce of prevention…

And it’s precisely these challenges that have Branch looking for answers. One of his current concerns is that black box of hemolysis, which affects about 35 per cent of patients (when including all grades).

“The goal for me is to see if we can put our finger on something that would be easy to test before patients get the IVIg to know who’s going to have a chance of hemolysis and who isn’t.”

Branch went on to explain that the varied responses point to something different within the patient’s immune system that changes, rather than the cause being present in the drug, which undergoes a rigorous standardization process.

Branch’s money – or at least his research – is on a cytokine, a type of small protein that is secreted by cells and can signal a particular action in other cells. In this case, the cytokine in question, named IL-1ra, is part of a family that is central to the body’s immune and inflammation response. His theory is that elevated levels of IL-1ra prior to receiving IVIg may be a signal of higher risk that the patient will experience a hemolytic reaction.  

Of course, there may be other cytokines that herald a hemolytic episode in response to IVIg therapy; that is why Branch is investigating 40 different cytokines in a Canadian Blood Services’ funded prospective study of patients receiving IVIg for various conditions.

Another test that is being used by Branch is one that he pioneered and continues to use. “We are using a test called the monocyte monolayer assay, which I pioneered way back when, to look at activation of the patient’s monocytes,” said Branch. Monocytes and macrophages are types of white blood cell – one of the defensive cells that identifies and attacks foreign intruders in the bloodstream, and is chiefly responsible for the unwanted attack on red blood cells in the case of IVIg-associated hemolysis.

“The idea,” said Branch, “is that we can actually measure whether or not the patient’s monocytes are more active than not and thus predict whether a hemolytic response would occur.”

It’s only one thing to look for, however. Another indicator of an adverse reaction to IVIg treatment is the presence of a mutation on the monocytes/macrophages that creates a heightened sensitivity to antibodies present on red blood cells, thereby increasing the likelihood of an immune attack. This mutation can be detected through a DNA test, but it takes longer to obtain the results than the monocyte test.

Branch is also involved in a fourth area of interest, in collaboration with Dr. Elisabeth Maurer, founder of LightIntegra Technologies, which is examining levels of microparticles as a measure of an inflammatory condition existing prior to receiving the IVIg.

Pulling one or more of these indications into standard tests that could be administered to patients in advance of an IVIg treatment would enable medical professionals to avoid an adverse hemolytic reaction and would go a long way in helping us understand the mechanism of IVIg-mediated hemolysis.

The hunt for alternative treatments

While greater understanding will inevitably help reduce risk for patients and costs for the health care system, it does little to address the cost of the therapy in Canada, given that plasma donation is only a fraction of what’s needed.

Currently, plasma donated at many Canadian Blood Services collection sites is sent to the US  or Europe for processing, in part due to this lack of volume, but also because no such facility yet exists in Canada. Globally, there is enough IVIg to spare, but it is an expensive treatment option, which is one reason the number of illnesses approved for IVIg therapy is relatively small.

IVIG is licensed by Health Canada for treatment of primary and secondary immune deficiencies, allogeneic bone marrow transplantation, chronic B-cell lymphocytic leukemia, pediatric HIV-infection, Kawasaki disease and idiopathic thrombocytopenic purpura. There are many “off-label” (not on Health Canada’s licensed list) uses for IVIG, which may account for a sustained demand in Canada. 

It’s also why Branch and a number of others are seeking alternatives. Branch is looking to drug discovery that might help prevent an adverse immune response in the blood. But he predicts that a non-plasma IVIg replacement may not be too far away.

“One bit of published work  involves making a recombinant protein [essentially a protein obtained from DNA mixed to get a desired product] that they think is the effector molecule, and they showed it works tenfold better in animal models than does IVIg. And not just in immune thrombocytopenia (ITP) but in an arthritis mouse model and autoimmune psoriasis, showing that the recombinant protein worked extremely well in all of these different models.”

Assuming that these studies can progress safely into the clinic, Branch has high hopes for what it will mean for medicine.

“It truly is a wonder drug,” he reiterated. “There’s aspirin. That was the first miracle drug. Then statins – the cholesterol drugs that’s the second one. And then, it’s IVIg.”

 

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Dr. Donald Branch is a Scientist with Canadian Blood Services’ Centre for Innovation. His lab is located at 67 College Street in Toronto. He is also an Associate Professor at the University of Toronto. Dr. Branch’s research aims to understand the pathogenesis and functioning of cells in various diseases that require blood transfusion products and related biologics. In particular, Dr. Branch studies mononuclear phagocytes to understand and inhibit the phagocytosis function of these cells in autoimmune diseases and, using animal models of autoimmune diseases, the mechanism of amelioration by intravenous immunoglobulin (IVIg) therapies.

 

Keywords: IVIg, intravenous immunoglobulin, autoimmune, research, plasma, science


Canadian Blood Services – Driving world-class innovation

Through discovery, development and applied research, Canadian Blood Services drives world-class innovation in blood transfusion, cellular therapy and transplantation—bringing clarity and insight to an increasingly complex healthcare future. Our dedicated research team and extended network of partners engage in exploratory and applied research to create new knowledge, inform and enhance best practices, contribute to the development of new services and technologies, and build capacity through training and collaboration.


About the Author: Lisa Willemse is a communications professional with 18 years’ experience working in the technology, child development and health research fields, and is currently a Senior Communications Advisor with the Ontario Institute for Regenerative Medicine. With a background in fine art, communications and journalism, Lisa continues to moonlight as a writer, photographer and editor, contributing to a range of Canadian and US-based publications. In 2014, she was invited alumni-in-residence for the acclaimed Science Communications program at the Banff Centre. Follow her on Twitter and Medium @WillemseLA


The opinions reflected in this post are those of the author and do not necessarily reflect the opinions of Canadian Blood Services nor do they reflect the views of Health Canada or any other funding agency.

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