Sarah-Kate Templeton, Health Editor
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Obama: I believe that the restrictions that President Bush has placed on funding of human embryonic stem cell research have handcuffed our scientists and hindered our ability to compete with other nations. As president, I will lift the current administration's ban on federal funding of research on embryonic stem cell lines created after August 9, 2001 through executive order, and I will ensure that all research on stem cells is conducted ethically and with rigorous oversight.
More here.
]]>Scientists Reprogram Adult Cells' Function
Advance Stirs Up Debate on Embryos
By Rob Stein
Washington Post Staff Writer
Thursday, August 28, 2008; A01
Scientists have transformed one type of fully developed adult cell directly into another inside a living animal, a startling advance that could lead to cures for a variety of illnesses and sidestep the political and ethical quagmires
associated with embryonic stem cell research.
Through a series of painstaking experiments involving mice, the Harvard biologists pinpointed three crucial molecular switches that, when flipped, completely convert a common cell in the pancreas into the more precious insulin-producing ones that diabetics need to survive.
The experiments, detailed online yesterday in the journal Nature, raise the prospect that patients suffering from not only diabetes but also heart disease, strokes and many other ailments could eventually have some of their cells reprogrammed to cure their afflictions without the need for drugs, transplants or other therapies.
"It's kind of an extreme makeover of a cell," said Douglas A. Melton, co-director of the Harvard Stem Cell Institute, who led the research. "The goal is to create cells that are missing or defective in people. It's very exciting."
The work was hailed as a welcome development even by critics of research involving embryonic stem cells, which can be coaxed to become any tissue in the body but are highly controversial because they are obtained by destroying embryos.
"I see no moral problem in this basic technique," said Richard Doerflinger of the U.S. Conference of Catholic Bishops, a leading opponent of embryonic stems cell research. "This is a 'win-win' situation for medicine and ethics."
Researchers in the field, who have become accustomed to rapid advances, said they, too, were surprised by the advance.
"I'm stunned," said Robert Lanza, chief scientific officer of Advanced Cell Technology in Worcester, Mass., a developer of stem cell therapies. "It introduces a whole new paradigm for treating disease."
Melton and other researchers cautioned that many years of research lay ahead to prove whether the development would translate into cures.
"It's an important proof of concept," said Lawrence Goldstein, a stem cell researcher at the University of California at San Diego. "But these things always look easier on the blackboard than when you have to do them in actual patients."
Although the experiment involved mice, Melton and other researchers were optimistic that the approach would work in people.
"You never know for sure -- mice aren't humans," said George Q. Daley, a stem cell researcher at Children's Hospital in Boston. "But the biology of pancreatic development is very closely related in mice and humans."
Melton has already started experimenting with human cells in the laboratory and hopes that within a year he can start planning the first studies involving people with diabetes. "I would say within five years, we could be ready to start human trials," Melton said.
Other scientists have begun trying the approach on other cells, including those that could be used to treat spinal cord injuries and neurogenerative disorders such as Lou Gehrig's disease.
"The idea to be able to reprogram one adult neuron type into another for repair in the nervous system is very exciting," said Paola Arlotta, who is working in the Center for Regenerative Medicine at Massachusetts General Hospital-Harvard Medical School in Boston.
The research is the latest development in the explosive field of regenerative medicine, which seeks to create replacement tissues and body parts tailored to patients. That objective appeared within reach after scientists discovered stem cells. But stem cell research has been hampered by objections from President Bush and others who believe that the earliest stages of human life have moral standing.
Scientists last year shocked the field when they announced they had discovered how to manipulate the genes of adult cells to turn them back into the equivalent of embryonic cells -- entities dubbed "induced pluripotent stem" or "iPS" cells -- which could then be coaxed into any type of cell in the body.
The new work takes further advantage of the increasing ability scientists have developed in harnessing the once-mysterious inner workings of cells -- this time to skip the intermediary step of iPS cells and directly transform adult cells.
"This experiment proves you don't have to go all the way back to an embryonic state," Daley said. "You can use a related cell. That may be easier to do and more practical to do."
Doerflinger argued that the discovery was the latest evidence that research involving human embryos is no longer necessary. "This adds to the large and growing list of studies helping to make embryonic stem cells irrelevant to medical progress," Doerflinger wrote in an e-mail.
But other researchers disputed that, saying it remains unclear which approach will ultimately prove most useful.
"Embryonic stem cells offer a unique window in human disease and remain a key to the long-term progress of regenerative medicine," Melton said.
For their work, Melton and his colleagues systematically studied cells from the pancreas of adult mice, slowly winnowing the list of genes necessary to make a "beta" cell that produces insulin. After narrowing the candidate genes to nine, the researchers genetically engineered viruses known as adenoviruses to ferry the genes into other pancreatic cells, known as exocrine cells, which normally secrete enzymes to help digest food. That finally enabled the researchers to identify the three crucial genes needed take control of the rest of the cell's genes to convert an exocrine cell into a beta cell.
"It was a mixture of work, luck and guessing," Melton said. "We achieved a complete transformation, or re-purposing, of cells from one type to another. We were delighted."
When the scientists tried the approach on diabetic mice, the animals became able to control their blood sugar levels.
"It didn't cure the mouse, but they were able to reduce their blood sugar levels to near-normal," Melton said.
Melton and others said it remains to be seen whether it will be necessary to use genetically engineered viruses, which could face obstacles obtaining regulatory approval because of concerns about unforeseen risks, or whether chemicals might be found to do the same thing.
If preliminary studies in the laboratory are promising, Melton said he might first try converting liver cells to insulin-producing pancreatic cells, because that would be safer than using the pancreas. An alternative strategy would be to use the approach to grow beta cells in the laboratory and transplant them into patients.
Lanza said he is optimistic.
"One day, this may allow the doctor to replace the scalpel with a sort of genetic surgery," Lanza said. "If this can be perfected, it would represent one of the holy grails of medicine."
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NEW YORK (AP) -- Harvard scientists say they have created stems cells for 10 genetic disorders, which will allow researchers to watch the diseases develop in a lab dish.
This early step, using a new technique, could help speed up efforts to find treatments for some of the most confounding ailments, the scientists said.
The new work was reported online Thursday in the journal Cell, and the researchers said they plan to make the cell lines readily available to other scientists.
Dr. George Daley and his colleagues at the Harvard Stem Cell Institute used ordinary skin cells and bone marrow from people with a variety of diseases, including Parkinson's, Huntington's and Down syndrome to produce the stem cells.
The new cells will allow researchers to "watch the disease progress in a dish, that is, to watch what goes right or wrong," Doug Melton, co-director of the institute, said during a teleconference.
"I think we'll see in years ahead that this opens the door to a new way to treating degenerative diseases," he said.
The new technique reprograms cells, giving them the chameleon-like qualities of embryonic stem cells, which can morph into all kinds of tissue, such as heart, nerve and brain. As with embryonic stem cells, the hope is to speed medical research.
Research teams in Wisconsin and Japan were the first to report last November that they had reprogrammed skin cells, and that the cells had behaved like stem cells in a series of lab tests. Just last week, another Harvard team of scientists said they reprogrammed skin cells from two elderly patients with ALS, or Lou Gehrig's disease, and grew them into nerve cells.
Melton said the new disease-specific cell lines "represent a collection of degenerative diseases for which there are no good treatments and, more importantly, no good animal models for the most part in studying them."
A new laboratory has been created to serve as a repository for the cells, and to distribute them to other scientists researching the diseases, Melton said.
"The hope is that this will accelerate research and it will create a climate of openness," said Daley.
He expects stem cell lines to be developed for many more diseases, noting, "this is just the first wave of diseases." Other diseases for which they created stem cells are Type 1, or juvenile, diabetes; two types of muscular dystrophy, Gaucher disease and a rare genetic disorder known as the "bubble boy disease."
Daley stressed that the reprogrammed cells won't eliminate the need or value of studying embryonic stem cells.
"At least for the foreseeable future, and I would argue forever, they are going to be extremely valuable tools," he said.
The reprogramming work was funded by the National Institutes of Health and private contributions to the Harvard Stem Cell Institute.
Background: Not all children in need of a haematopoietic stem cell transplant have a suitable relative or unrelated donor available. Recently, in vitro fertilization (IVF) with pre-implantation genetic diagnosis (PGD) for human leukocyte antigen (HLA) tissue typing has been used to selectively transfer an IVF embryo in order to produce a child who may provide umbilical cord blood for transplantation to an ill sibling. Such children are sometimes called "saviour siblings".
Objective: To examine the published clinical and epidemiological evidence relevant to the use of this technology, with the aim of clarifying those situations where IVF and PGD for HLA-typing should be discussed with parents of an ill child.
Design: A critical analysis of published literature on: comparative studies of umbilical cord blood versus other sources of stem cells for transplantation; comparative studies of matched unrelated donor versus matched related donor transplantation; and the likelihood of finding an unrelated stem cell donor.
Conclusion: IVF and PGD for HLA-typing is only applicable when transplantation is non-urgent and parents are of reproductive age. Discussions regarding this technology may be appropriate where no suitable related or unrelated donor is available for a child requiring a transplant, or where no suitable related donor is available and transplantation is only likely to be entertained with a matched sibling donor. Discussion may also be considered in the management of any child lacking a matched related donor who requires a non-urgent transplant or may require a transplant in the future.
Should baby be risked for sister?
She could be released from it by a sibling, but the sibling is not yet conceived.
And can one child's health ever be put at risk to save another's?
When Catherine, the first child of Charles and Clara, was born in 2001, she seemed healthy - but not for long.
"She was very listless and would fall asleep in the middle of a feed," said her mother.
"When she was 11 weeks old, she was pretty much pure white, you couldn't even see her lips. We took her into A&E."
Tests revealed that Catherine had virtually no red blood cells.
She was eventually diagnosed with Diamond Blackfan Anaemia (DBA), a genetic disease in which few if any red blood cells are produced by the bone marrow, producing anaemia.
DBA can be treated with day long monthly transfusions.
However, every transfusion adds iron to the body which will cause irreversible organ damage unless removed.
Removal involves giving a drug given as a continuous transfusion through a needle, all through the night, five nights a week.
"Catherine hated it, screaming 'I don't want it, I don't want it'," said Clara.
"She got used to it, but often said: 'Why can't I be normal'."
Risk of early death
DBA carries a one in four chance of early death because of organ damage and an increased risk of childhood cancer.
"Once we saw what her quality of life was and the problems that she might have in the future, we started saying is there something else we can do?", said Clara.
A bone marrow transplant was the only option.
One from an unrelated donor carried up to a 30% risk of death for Catherine, one from a related donor a 5% risk.
Charles and Clare had intended having another baby anyway and hoped that a baby brother or sister would be a tissue match.
With each pregnancy there is the same one in four chance of a match.
But it is possible to use a technique normally used in pre-implantation genetic diagnosis (PGD), in which a cell from the three-day-old embryo is taken to screen out serious genetic disease, for tissue typing, to guarantee that a sibling is a tissue match, before being replaced.
The uncertainty of IVF gives a one in 10 chance of successful pregnancy with such a match.
Spontaneous mutation
There was however a major problem: DBA can be inherited or arise as a spontaneous mutation.
Which sort did Catherine have?
There was no family history of the condition. Tests on Catherine showed she didn't have any of the known mutations that cause DBA, but there are some as yet uknown.
It meant that no-one could test whether another baby had the condition or not.
Not being able to rule out DBA was a major ethical issue.
So Clara and Charles decided to have a baby naturally. But the new baby wasn't a match.
By this time, Catherine was three and the couple were acutely aware that her condition was deteriorating.
She had to have a transplant before she became too sick to survive the procedure.
They decided to go for tissue typing. To do this they needed to have a licence from the Human Fertilisation and Embryology Authority.
But at the time, the HFEA only allowed PGD to be used for tissue typing where a disease could be screened out. This was not possible in Catherine's case.
So the couple went to the US, where it was permitted. But two attempts failed.
They were psyching themselves up for a third attempt, when they read about a UK couple in the same situation as themselves, who had been given a licence by the HFEA following a judicial review.
They decided to try for a 'saviour sibling' using PGD.
Devastating blow
The procedure of taking stem cells for a bone marrow transplant would not harm Catherine's sibling, because they could be obtained from cord blood at birth.
When baby sister, McKenzie was born, not enough stem cells could be collected for a transplant.
It was a devastating blow - but at least she was free from DBA.
"Every picture I took of them together had added meaning because Catherine was looking at her lifeline," said Clara.
A much more invasive collection of bone marrow from McKenzie involving 90 minutes of general anaesthesia was now required.
There is no benefit to the donor, and McKenzie was not able to provide consent.
The chances of success for Catherine were getting less as time went on, but the younger McKenzie was, the greater the risks of anaesthesia for her.
Competing interests
Here the ethical issues are the competing 'best interests' of the sisters.
There is also the issue that the donation will only cure Catherine's symptoms, not rid her of the condition.
There is a good chance it could fail. How would McKenzie feel later knowing that her donation failed to save her sister?
And should Catherine's kidneys fail, then once again, McKenzie would be the first choice of donor.
The Clinical Ethics Committee decided that the bone marrow transplant should go ahead. It took place 18 months ago.
It was a success and Catherine continues to do well.
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WASHINGTON (Reuters) - Cells taken from human bone marrow, blood and umbilical cords grew into functioning blood vessels in mice with just the right coaxing, U.S. researchers reported on Saturday.
The so-called progenitor cells teamed up to form working blood vessels that connected to the circulatory systems of the mice, the team at Harvard Medical School and Children's Hospital Boston reported.
"What's really significant about our study is that we are using human cells that can be obtained from blood or bone marrow rather than removing and using fully developed blood vessels," said Harvard's Joyce Bischoff, who led the study.
Her team used immature cells, known as progenitor cells, grown under special lab conditions before being implanted into mice. Once implanted, the cell mixture grew and differentiated into a small ball of healthy blood vessels, they reported in the journal Circulation Research, published by the American Heart Association.
They used endothelial progenitor cells, which mature into cells that line the blood vessels, and mesenchymal progenitor cells, which differentiate into the cells that surround the lining and provide stability.
A mixture of cells from adult blood and bone or from umbilical cord blood worked the best, they said.
They hope to find a way to help the body replace blocked or damaged blood vessels, such as arteries blocked in a heart attack or stroke.
"What we are most interested in right now is speeding up the vascularization," Bischoff said in a statement. "We see very good and extensive vasculature in seven days and we'd like to see that in 24 or 48 hours. If you have an ischemic tissue, it's dying tissue, so the faster you can establish blood flow the better."
(Reporting by Maggie Fox)
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Jul 13, 2008 by Nathan Bevan, Wales On Sunday
HE looks like any other seven-year-old with a happy-go-lucky gap-toothed grin.
But Rhys Harris, from Newbridge, has a special reason for such a big smile.
He's back home in Wales safe and well after almost a year away battling a rare killer disease. Doctors had given him only 18 months to live.
"Honestly, it's like he's never been away," said proud dad Kevin, a former car salesman who uprooted the entire family to Newcastle last October to be near one of only two hospitals in the UK where his son could get the specialist care he needed.
"Rhys couldn't wait to get back and had been counting down the days on a little calendar, just like he always does just before Christmas."
In December 2006, Wales On Sunday broke the news the Hollybush Primary School pupil had been diagnosed as having Nemo, a terminal condition that affects only 35 people in the world, attacking the body's immune system. We revealed how, after he contracted TB, his parents Kevin and Dawn were given the agonising choice of watching their son slowly die or risk him having a bone marrow transplant and the chemotherapy killing him instead.
"The doctors told us that if Rhys continued with his regime of drugs then he only had six months to a year left to live and, as parents, we just couldn't accept that," said Kevin, 44.
In September, Rhys' family were told a bone marrow match had been found in the US. Agonisingly, this meant Rhys would have to live in a special isolation "bubble" to stave off risk of infection, Kevin and his wife Dawn being unable to so much as give him a kiss.
But he recovered so quickly from the life-threatening surgery he was discharged after two months. Since then, Rhys has defied the odds and been declared free of Nemo.
"It's amazing," said an emotional Kevin last night. "To think, the day before his transplant I'd considered not signing the consent form because I'd rather he came home to die with dignity and have his family around him.
"But deep down I knew we could never give up hope," he added.
"Now, clinically speaking, we're more or less out of the woods. But because Nemo is so rare and not enough is known about it, the doctors are hedging their bets and keeping him on a course of drugs."
So what's next then for little Rhys?
"A family holiday and then it's back to school in September - he's excited about seeing his class mates again," said Kevin, who added that he was forever indebted for the tireless support he and his family had received throughout their gruelling ordeal.
"We had everything, from people in the Valleys sending £5 cheques in the post to the Benevolent Fund of the RAF, in which I served for a number of years, paying our mortgage for a year, as well as our rent on the Newcastle flat.
"When things like that happen it really restores your faith in humanity, knowing that so many people care.
"Now Rhys is better I want to get involved in charity work myself, and maybe do some good for other families who weren't as lucky as us."
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NFED's executive director, Mary K. Richter, spoke at the launch of Mexican Association of Ectodermal Dysplasias "Mariana" (Asociacion Mexicana de Displasia Ectodermica) on April 30th in Toluca, Mexico. She wished the organization well and gave some advice to Karla Carmona Prantl who founded the organization. She and her husband, Alejandro, have a daughter, Mariana, who is affected by hypohidrotic ectodermal dysplasia, and a son, Alejandro.
Mary Kaye said, "On behalf of more than 5,000 families in 70 countries, I want to congratulate Karla on this extraordinary day celebrating the creation of a support organization for families affected by ectodermal dysplasia syndromes throughout Mexico....the Asociacion Mexicana de Displasia Ectodeermica...My wish for Karla is the courage to struggle on when times are difficult, the wisdom to know what to do and when, the patience and understanding to know that this is not a daylong journey but one of years and the support, assistance and love from her family, friends and anyone who can help her in any way possible. With all of that, success will be yours.........but more importantly individuals in Mexico affected by ectodermal dyplasia will live fuller, happier, healthier and more successful lives."
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Jun 12 2008 by Abbie Wightwick, South Wales Echo
He couldn't even have a hug from his mum for fear of infection, but after a lifesaving bone marrow transplant at Newcastle General Hospital little Rhys Harris is on the mend. Abbie Wightwick finds the family is now making plans to return to Wales...
RHYS Harris spent two months in an airtight bubble in an attempt to save his life but now he's back playing rugby and tucking into his favourite meal of roast chicken after fighting a rare genetic disease.
The seven-year-old from Newbridge, Caerphilly, who could not even have a hug from his mum for fear of infection, has been cared for by doctors in Newcastle since last October.
Dad Kevin, 44, mum Dawn, 39, and brother Morgan, five, all moved north to be with him for a lifesaving bone marrow transplant.
Now doctors at Newcastle General Hospital say Rhys is on the mend at last and the family plans to return to Wales in the next couple of months.
Consultant Dr Mario Abinum said he would not know whether Rhys had been cured until further tests in the autumn, although it was "looking very positive".
"It's great news," Dr Abinum said.
"Rhys is great. He's doing OK and putting on weight. We can't say he's cured because it's only seven months since the transplant.
"We need to do more at 12 months. But so far everything is excellent."
This time last year Rhys was dying from the genetic disease Nemo, which attacked his immune system leaving him unable to fight infection.
Doctors at the University Hospital of Wales in Cardiff got in touch with Professor Andrew Kent in Newcastle who advised a bone marrow transplant.
A desperate hunt against the clock then began for a match. But even when a match was found in the USA, Kevin and Dawn were unable to celebrate.
Kevin wanted to pull out on the day the transplant was scheduled, fearing the risks which could also kill his son.
"You should be elated but as a parent you then have to ask whether you will put your child through it all," Kevin said. "We had to make the decision to sign a bit of paper that could have been Rhys' death warrant.
"Until the day of the transplant I was still going to pull out. Do you let your child die with dignity or let him go through chemotherapy? Chemotherapy is a horrible thing and so is isolation.
"We had a terrible week and then Professor Kent just told me there was no option. He sat me down and changed my mind.
"He is the only person who could change my mind. He is a wonderful man.
"Now we are out the other end. We have a life with Rhys now that was not with us last year.
"We have a future now that we were told we would never have this time last year. We can plan ahead.
"I can get home and get a job and Rhys can go to school."
In the meantime, Rhys, a pupil at Hollybush Primary in Cwmbran, is enjoying finding his feet in the world again, playing in the park and meeting other children.
During his two months in isolation, Rhys could not even be comforted with a cuddle from his mum because his immune system had been killed off by chemotherapy.
Before the bone marrow transplant pumped a new immune system into his body, any bug could have killed him.
His parents are still wary when people cough nearby, but they can take Rhys to kick his treasured rugby ball in the park again.
"He's able to interact with other children now. But until the tests in October, which will be a year since the transplant, we will be on edge a bit," Kevin said.
"We can't really say the 'c' word for cure yet but it's positive news and Rhys is home with us.
"Rhys plays rugby but is not able to go back to school yet. A tutor comes to the house twice a week. He's a normal seven-year-old boy and he needs challenges. We try to keep contact with his friends in Wales. He misses them.
"I try to go home every couple of months. It's very odd.
"We've made a life for ourselves here now. Morgan goes to school here and the other parents have been so supportive.
"We're looking forward to going back; it will also be hard. When you go through an experience like we have, the place you're in becomes very poignant. It's beautiful up here and the people are lovely."
Rhys was left profoundly deaf by meningitis when he was small, and Kevin was training to be an audiologist and studying for a degree when he fell ill with Nemo.
Now Kevin wants to take his life off hold.
He has been studying sign language and Spanish and wants to work for a charity.
"You have to do something else. I like nothing more than going for a run or out on my bike. I had to do something with my time when I stopped working.
"Rhys needed us to help pull through. The whole of Wales has helped pull him through too. The Cardiff Blues, Ospreys, the Dragons, the WRU and the whole Welsh rugby team spoiled him and made a fuss of him.
"They helped to make a little child happy and I think that helped him to keep strong.
"If it was not for people being like that I honestly don't think he would be here today. A smile is as good as medicine."
Kevin now wants to increase awareness about the bone marrow register and get more people to sign up as potential donors.
"At any one time 7,500 people in the UK need a bone marrow transplant. It's a transfusion not a transplant. We would get thousands more people immediately if they called it a transfusion. People get put off by the word transplant.
"The whole of Pontypridd Rugby Club are all on the register now.
"If someone went past a river and saw a child in there 99% would go in and help."
That is one reason why Kevin and Dawn have always kept good relations with the media. They hope the exposure may highlight the need for more donors.
Last week they were besieged by the world's media after someone wrongly reported Rhys had been "cured".
Dawn and Kevin admitted it all got a bit much.
"Dawn and I are very private people but we made a conscious decision to talk to the media to help find a bone marrow donor that matched," said Kevin.
"It's not easy to talk about what we've been through, especially for my wife.
"But we decided we had to do it. It was part of our mission to find a donor."
Dawn, like any mother, now wants what seemed an impossible dream a year ago.
"Hopefully, Rhys will have a long and happy life," she said.
Rhys Harris, 7, from Newbridge, south Wales, has survived treatment, which has given him a new immune system.
Rhys had to endure living in a 'plastic bubble' - which ensured he was kept in sterile isolation - for two months, meaning his parents couldn't touch him.
Rhys was diagnosed with an incurable genetic disease called NEMO which affects the immune system and other organs of the body, when he was three.
The disease, of which there have only been 40 reported cases since 2001, rendered his immune system deficient.
Experts at Newcastle General Hospital gave young Rhys only a one in three chance of survival.
However, when a bone marrow was found in the United States, Rhys underwent a life saving transplant - before which his own bone marrow was killed by chemotherapy.
Mario Abinun, Consultant Paediatric Immunologist at Newcastle General Hospital said that Rhys "has already gotten over a few hurdles and all the indicators and laboratory reports show he is doing fine".
Mr Abinun added that Rhys will not be given a clean bill of health until at least the autumn.
Rhys' father, Kevin, 44 said he knew it was a "slim chance" the treatment might work but he and his wife, Dawn, had to take it.
"The flipside of the coin just wasn't worth thinking about," he said.
(DS)
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]]>- John Kenneth Galbraith, economist
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