Scientists have used artificial intelligence to uncover new types of antibiotics in the face of growing concerns about resistance to the drugs.
A group of researchers from Massachusetts Institute of Technology (MIT) say their machine-learning algorithm was able to identify a powerful new antibiotic compound, capable of killing some of the world’s most problematic disease-causing bacteria.
They claim the technology is able to work more quickly and efficiently than existing systems, because it checks more than a hundred million chemical compounds in a matter of days to pick out potential antibiotics that kill bacteria.
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The AI was trained specifically to track down possible antibiotic molecules known for being effective against E.coli growth.
“We’re facing a growing crisis around antibiotic resistance, and this situation is being generated by both an increasing number of pathogens becoming resistant to existing antibiotics, and an anaemic pipeline in the biotech and pharmaceutical industries for new antibiotics,” said MIT’s Professor James Collins, who is also co-founder of an antibiotic drug discovery firm EnBiotix.
“We wanted to develop a platform that would allow us to harness the power of artificial intelligence to usher in a new age of antibiotic drug discovery.
“Our approach revealed this amazing molecule which is arguably one of the more powerful antibiotics that has been discovered.”
The molecule, named halicin, proved effective against E.coli, which did not develop any resistance to it during a 30-day treatment period on mice.
Researchers, who published their paper in the Cell journal, say they want to study halicin further in hope of developing it for use in humans.
Jacqueline Wilson has responded with delight to Stormzy sampling the Tracy Beaker theme tune on his track “Superheroes”.
At the end of the song, Big Mike can be heard singing Keisha White’s “Someday”, which is best known for being the theme of the popular children’s TV show.
“What a treat to hear the Tracy Beaker theme tune popping up on @stormzy song. Love it!” wrote the author of the original books on Twitter.
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Stormzy then responded with: “Ayeeeee JACQUELINE WILSON ya na!!! Real ones know!! what a legend!!”
Tracy Beaker ran from 2002 to 2005 and starred Dani Harmer as the eponymous young rebel living in a care home.
Stormzy’s song “Superheroes” features on his new album Heavy is the Head, which was released on Friday 13 December.
It was awarded four stars by The Independent’s critic Roisin O’Connor, who wrote: “Not only is it a drastic step up from his impressive debut, but it shows an artist keen to test himself emotionally, as well as artistically.”
Some procurers, however, may take deeper cuts of skin that are more disfiguring, and may expose muscles, fascia and other structures. They may later separate the skin into a thin layer for grafts for burn victims, and a layer of dermis to be used in procedures like breast reconstruction after mastectomy.
Since there are usually no recipients waiting for skin, as there may be for organs like kidneys, the sheets are usually wrapped in gauze, folded, packaged individually, labeled and frozen. Donated skin can be kept this way up to five years.
The frozen sheets are thawed in a warm bath of saline before use on a patient, when they are stapled, sutured or glued on, Dr. Shahrokhi said.
To treat a burn patient, the surgeon removes dead skin as soon as the patient is stabilized, in order to prevent life-threatening infections like sepsis.
But the donor skin graft that is applied is only a temporary patch; it will be rejected by the patient’s immune system within a matter of weeks. Still, it provides the protective function of healthy skin: closing the wound, protecting against infections and fluid loss, decreasing pain and promoting healing.
Ultimately, the donor skin, called an allograft, must be replaced with an autograft, skin taken from another part of the patient’s own body.
Human skin is expensive. A single square centimeter can cost a hospital about $2.82, depending on the source, according to Mag Tait, director of the Trauma Burn Laboratory at Michigan Medicine.
“I think for all of us it means an attention more on craft, on creativity, and less on the idea of clothes that are instantly disposable, things that you will throw away just after one reading,” Wintour said.
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“[It’s all about] talking to our audiences, our readers, about keeping the clothes that you own, and valuing the clothes that you own and wearing them again and again, and maybe giving them on to your daughter, or son, whatever the case may be.”
Patricia Espinosa, executive secretary of UN Climate Change, welcomed the move, stating that Condé Nast’s involvement will be “very valuable to disseminate information about the sustainability efforts and achievements of the fashion industry as well as informing the world about the need for wider and accelerated climate action”.
As part of its pledge, Condé Nast will encourage consumers to re-use clothes, support sustainable fashion and the use of pioneering materials, the UN stated.
Earlier this year, the government launched a cross-party group for sustainable clothing and textiles.
The aim of the All Party Parliamentary Group, which was launched with the support of sustainability charity Hubbub, is for MPs from all different parties to review supply chains, materials used and consumer behaviour.
The deal, which is reportedly the first of its kind in the luxury industry, allows the Italian fashion house to alter its interest rates on an annual basis depending on if it achieves certain eco-friendly objectives.
During her interview with Reuters, Wintour also spoke about the way in which fashion has developed with regards to diversity and inclusivity, saying that in her opinion, the industry has been “a little bit late in the game”.
The Condé Nast artistic director stated that while she acknowledges progress has been made, she believes the profession has a “long way to go”.
“We are seeing a far more diverse and inclusive representation on the runway, on our social media channels and also in the pages of our different magazines,” she said.
“I think a lot of that has to do with the fact that we have so many designers of colour in the United States.
“Until there is truly a voice at the table things will not change the way that they should. I feel we have a long way to go.”
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School has started, pumpkin spice is everywhere and it’s that awkward phase where it’s too risky to leave your jacket at home, but wearing it leaves you sweating to death.
While some might call it autumn, for us it means one thing: the countdown to Christmas has begun.
For beauty junkies, this countdown has only got more exciting in recent years, as traditional advent calendars have been injected with a bit more glamour and luxury. Beauty advent calendars seem to have sprung up from nowhere, but nobody’s complaining when you can wake up to a different lipstick every morning.
To find our top choice for 2019, our tester learnt from her beauty mistakes of Christmas past. While quantity can seem tempting, ideally we want 24 different products destined to become lifelong staples in our beauty routine.
Similarly, the bigger the products, the better – while a lot of mini products seems fun, the reality is that most find their homes at the bottom of your handbag. Eager to find our new favourite, we dove into the Christmas season early and opened hundreds of calendar doors to find the best on offer this year.
You can trust our independent reviews. We may earn commission from some of the retailers, but we never allow this to influence selections, which are formed from real-world testing and expert advice. This revenue helps to fund journalism across The Independent.
Feelunique 24 day beauty advent calendar: £79, Feelunique
Beauty website Feelunique has been in the advent calendar business for a while now and its 2018 offering sold out in two weeks. This year the brand has introduced two options – a 12 days and 24 days calendar –with the latter offering £250 worth of some of the site’s top-selling products. Behind the Northern Lights-inspired packaging, there’s a lot of impressive brands, including Nuxe, Shiseido and Huda Beauty. While we won’t ruin the surprise of what’s behind door 24, we can promise it’s more than worth the wait.
Charlotte Tilbury glittering galaxy of make-up magic: £150, Charlotte Tilbury
Anyone looking to be the most glamorous person in the room on Christmas day will love this Charlotte Tilbury offering. The galaxy-inspired calendar features the products to create two different makeup looks, including four full-size products. While there are only twelve days, quality is favoured over quantity – we especially loved the inclusion of eyes to mesmerise cream eyeshadow and Charlotte’s cult-classic moisturiser, magic cream. The excessive glitter on the packaging also doesn’t hurt, making a jaw-dropping addition to your Christmas decor.
It doesn’t get much cuter than Cath Kidston’s advent calendar. Decorated in a festive-rendition of its trademark illustrations, it contains everything you need to treat yourself over the season, with its contents ranging from body lotions and soaps to hand creams and bath bombs. The brand also offers a more luxe option for £80, shaped like a Christmas house.
You can always rely on L’Occitane to design high-quality gifts that look as good as they feel. This year there are two different calendars to choose from, but our favourite is the 24 day calendar. Travel-sized versions of its most popular products take you all the way up to the big day, as well as following the calendar’s “tree of dreams” story that delivers different tips on how to nurture nature. Every product is ideal for slipping into your bag for any last-minute beauty emergencies, and our tester’s skin felt better than ever after just a few days.
The Body Shop dream big this Christmas deluxe advent calendar: £65, The Body Shop
The Body Shop has outdone itself this year, releasing three advent calendar options – original, deluxe and ultimate. While all three are impressive in their own right, our pick is the deluxe, which balances luxury with affordability. With 25 treats from the Body Shop’s make-up, skincare and bath and body collections, there’s also the addition of daily trivia behind each door to celebrate the achievements of brilliant women throughout history. Once the big day’s come, you can also take each box and make it into your own Christmas village. It doesn’t get much more festive than that.
Elemis 25 days of beauty advent calendar: £165, Elemis
We absolutely love Elemis products at any time of year, but when 25 of the brand’s very best products are packed into a Christmas tree-shaped calendar it’s almost too much to handle. Anyone looking to elevate their skincare in 2020 is given the perfect introduction to a multi-step routine. It may be pricey but you can feel the quality in even the smallest of the travel-size products, and the final gift is one of the best we’ve seen in any calendar, leaving your skin glowing well into March.
Skincare fanatics will see this advent calendar as a whole Christmas wrapped into one. Eight full-size products and 16 deluxe minis promise to smooth, refine and hydrate your skin against the harsh winter weather, with our tester most excited about the inclusion of the brand’s phytopeel exfoliating cream. It may not be the most Christmassy of the bunch, but a worthy investment for your skincare collection.
Morris and Co. mixed prints beauty advent calendar: £40, John Lewis & Partners
A selection of William Morris’ most iconic prints decorate this calendar, which features a range of beauty favourites in three scents: golden lily, strawberry thief and library of prints. Not only does it slip seamlessly into festive decor, but it’ll leave you smelling great for months to come.
This is Paul & Joe’s third advent calendar, practically making the brand veterans in the beauty industry. It’s therefore unsurprising that it has perfected the curation of products. Lipsticks, skincare, eyeshadows and more are decorated with the brand’s iconic chrysanthemums and cats, delivering high-quality additions to your make-up bag.
As reliable as the brand’s stellar reputation suggests, the M&S beauty advent calendar is stuffed with make-up and skincare favourites. The brand’s own beauty line and cult classics like REN, This Works and L’Occitane bulk out the 24 days, worth over £300 in total. It has a more affordable price point than most of its competitors, costing just £40 when customers spend £25 on anything but food. We’d recommend this to skincare aficiendos in particular.
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Latest in Beauty 24 days of LIBmas: £65, Latest in Beauty
Beauty subscription service Latest In Beauty has pulled out all the stops to celebrate “LIBmas”. Wrapping 24 products up into a present-like box, an impressive 50 per cent of them are full-size. True to the spirit of subscription boxes themselves, there are plenty of surprises and new cult-classics to be discovered inside. As if that wasn’t enough, subscribers to the service can get a £7 discount and entry into a pre-order giveaway.
This calendar may be the cheapest offering on the list, but manages to feel like one of the most luxurious. Glossy hair and soft skin is unlocked with each of the seven doors of Moroccanoil’s calendar. Available from the end of October, every travel-size product inside is destined to become a must-have in our tester’s daily routine from now on.
Worth over £370 but only costing a fraction of the price, you’ll be ready for any occasion the festive season throws at you thanks to the Glossybox calendar. Big brand names like Chloé, NYX and Dermalogica have contributed the best of their collections to this baby pink beauty, and you can expect an exciting offering from Tarte Cosmetics on the big day itself. While it’s £80 for non-subscribers, those who have already caught onto the thrill of monthly subscription boxes (basically advent calendars you don’t have to wait until Christmas to open) can get it for a £10 discount.
Space NK launched its first advent calendar to mass hysteria in 2018, so it only makes sense that it’s back and bigger than ever. This is an anthology of its best products, so expect luxuries from the likes of Hourglass, Kate Sommerville, Drunk Elephant and more. While this definitely lies on the luxe side of the pricing scale, everything inside is as premium as any Space NK store. Serious beauty fans will feel like a child on Christmas Day for the whole advent season.
ASOS stocks some of the best beauty brands in the business, so its advent calendar was never going to be anything short of incredible. With 25 products from brands such as The Ordinary, NARS and Becca, this calendar feels luxe on a budget thanks to plenty of full-size offerings alongside its miniatures. It’s packaged inside a 100 per cent recyclable box that’s easy to reuse after, cutting down on plastic waste, and also feels a lot more practical than some of its competitors. It may not look the most festive, but definitely feels like a gift.
Natural skincare brand Nuxe has pulled out all the stops this year, offering everything from hand cream to face masks. What sets this apart from others its inclusion of all lines, including the men’s skincare. We’re already obsessed with the brand’s famous orange-blossom and vanilla scent and are particularly big fans of the multi-tasking body oils too.
IndyBest product reviews are unbiased, independent advice you can trust. On some occasions, we earn revenue if you click the links and buy the products, but we never allow this to bias our coverage. The reviews are compiled through a mix of expert opinion and real-world testing.
Black Friday 2019 is nearly here. Read our guide on how to get the best deals.
Approximately 1.4m British people are using “street cannabis” to treat medically-diagnosed chronic health conditions, a poll has found.
Previous research estimated between 50,000 and 1.1m people in the UK regularly use cannabis bought illegally as a form of medicinal treatment.
However, according to a new study of the “largest ever polling sample”, a greater number than estimated are purchasing cannabis outside of the law as a means of treating chronic health issues.
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A national survey of more than 10,000 people conducted by YouGov for the Centre for Medicinal Cannabis (CMC) and the Cannabis Advocacy and Support Services (CPASS) concluded that around 2.8 per cent of Britain’s adult population use street-available cannabis to treat medical problems.
According to the study’s findings, more than half of the adults using street-bought cannabis to treat chronic health conditions said they do so on a daily basis and just under a quarter said they do so on a weekly basis.
Nine per cent of the respondents said they spend nothing on cannabis, suggesting they grow their own supply.
Meanwhile, 44 per cent said they spend up to £99 a month on cannabis, while just over a fifth said they spend between £100 and £199 on cannabis every month.
Dr Daniel Couch, medical lead at the CMC, said that “robust clinical evidence” is needed to “evaluate the safety and efficacy of cannabinoid medicines”.
“For the first time we have reliable, representative data regarding the number of people in Britain using cannabis as a medicine,” Dr Couch said.
“The findings are astounding and present a national challenge.”
Ann Keen, chair of the CPASS and fellow of the Queen’s Nursing Institute, said: “[The statistics] demonstrate the vast number of patients in the UK with chronic and debilitating diagnosed conditions who feel they have no choice but to expose themselves to all the risks of accessing a medicine that works from the criminal market”.
Ms Keen added that “safe” solutions “must be explored as soon as possible”.
It was recently reported that two cannabis-derived medicines have been approved for use on the NHS for the first time.
The approved medicines will be used to help treat severe forms of childhood epilepsy and complications from multiple sclerosis.
Following the release of its poll, the CMC is due to outline new proposals for how the National Institute for Health and Care Excellence (NICE) can better assess cannabis-based medicinal products over the next five to 10 years.
More than 80 per cent of the respondents of the survey were from England, although the findings represent adults in the general population living in England, Wales and Scotland.
The latest Apprentice candidate to be fired by Lord Sugar has been revealed – and she’s extremely happy about it.
For the show’s fourth challenge, the candidates were asked to manufacture and sell bikes, which ended with record-breaking sales of over £1m for the winning team.
Things didn’t end too well for 33-year-old chartered accountant Lubna Farhan, though, who was sent home after being brought back to the boardroom by project manager Thomas Skinner.
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Following her firing, we spoke with Lubna about her reason for being so quiet on the show, why she couldn’t be bothered to fight for attention and whether there’s any truth to reports about a feud with controversial candidate, Lottie Lion.
How are you?
I’m okay now that I’ve been fired.
Why do you think Lord Sugar chose to get rid of you?
I think he fired me because he’s got good instincts and he could tell I wasn’t putting everything I had into the process. I wasn’t the reason for the failure of the task, but I didn’t have the will power to say so and I think that showed.
Did you expect to go when you were brought back into the boardroom?
One hundred per cent. I expected to go on the first day when I woke up on that task. When I woke up, my watch stopped working and I just knew that my time on The Apprentice was up. I knew if we failed this task, I was going home. It was like destiny – I could foresee it happening and it happened.
Were you secretly hoping to be fired?
I wasn’t secretly hoping; I was just really expecting it. It was very, very difficult for me to concentrate in the process, because I’ve got two kids who are two and one. Before The Apprentice, I was looking after them 24/7 on maternity leave, and then all of a sudden being thrown into a house with these extreme personalities and not being able to talk to them was very difficult. They’re all I could think about. I just couldn’t concentrate.
You did seem very quiet – I thought maybe that was because of the editing, but was it because you wanted to go home?
I felt like some people were attention seekers who just wanted to be in the limelight, and I just couldn’t be bothered to be a part of the drama they were trying to create. I did speak more in the previous episodes, so I would say some of it is the editing. I do feel that, in a way, the show’s edited to justify the firing. I was quiet on this task, but I couldn’t be bothered to compete with the strong personalities who wanted attention.
So were you relieved when Lord Sugar made his decision?
I was extremely relieved because I couldn’t really… I don’t want to say ”be bothered”, but I couldn’t, to be honest. I didn’t want to participate in the drama and overacting. Trying to be in the limelight and the loudest voice is just not me. I’ve worked with professional people all my life and I’ve never needed to behave like that. If I don’t overact in real life, why should I overact just because I’m on TV? That’s how I felt.
Were you too nice for The Apprentice?
I would say I was too nice compared to the people who were completely cutthroat, but at the end of the day, I decided to be myself. I don’t think being a nice person is a bad thing – a lot of times people would rather work with someone like me than someone who might be strong in the process, but not a nice person off-screen. There were two things I was definitely not going to do in the process, which I’m happy that I stuck by. One is grovel in front of Lord Sugar, and say “Please save me, keep me in the process.” I did not do that. The second thing – I wasn’t going to throw anyone under the bus and I’m happy I didn’t do that, either.
Why didn’t you want to grovel?
I’d like to think I know my worth. I’ve never had the need to grovel in front of anyone. I know that had Lord Sugar got to know me, there’s no one else he would have invested in, but I’m an introvert and it takes me time to open up. I was also so conscious coming into the process being a chartered accountant – I knew I had to behave professionally and be aware of the image I was giving out. I did hold back and there’s more I could have given, but I don’t regret anything.
You were lumbered with two of the biggest personalities of this year’s series. First up: Thomas. He was criticised by Marianne for being a dictator as Project Manager. Was that a fair argument?
I would say that he wasn’t a dictator in this task. Lord Sugar did ask him to listen more in the previous episode, and he did. It was the sub-team that didn’t actually listen to his instructions, so he naturally got really annoyed. I must say I do admire his ambition, determination and passion. I don’t really have anything negative to say about him.
He seems like a nice guy underneath the arrogance.
I think he is a nice guy. Let’s be honest here: he hasn’t been educated because of his background, but he’s done so well in terms of business. He actually had more manners than some of the other contestants who do come from educated backgrounds. I’d say that says a lot about how nice Thomas is. He was a gentlemen when some of the other candidates weren’t.
Then there’s Lottie. Was she frustrating to work with?
I would say that Lottie is a very strong candidate. It’s quite admirable that someone at her age has come into this difficult process. She has great instincts and is confident, articulate and can think on her feet. I think there’s a lot of positive things to say. Obviously, she is 19 and she’s quite feisty. I do think she has a lot to learn in terms of how to treat people, but I’m sure that during this process she will come to realise that at some stage. It’s actually good coming into this process at a younger age, because you’ve got the time to reflect before the rest of your life. It’s quite commendable.
There have been reports in the press about friction between you and Lottie in the run-up to this year’s series. Is there truth to the rumours?
I would say there is truth to it, however there’s no point me talking about it because it has already been spoken about.
Which candidate is getting away with the most?
I would say that everyone to some extent is getting away with one thing or the other, but I’m confident that Lord Sugar will be able to see past a lot of their tactics and techniques. He does give people a chance to mend their ways but if they don’t, they will be in the firing line.
If you had to predict who’ll make it to the final, who would you say?
Who I think can be in the final versus who I want in the final are probably two different things. I would love for Thomas to be there. He’s worked so hard and is great to watch.
Who do you reckon could win, then?
That’s a tough question because everyone in the process is so confident and are good at what they do. Anyone has a chance, really. I’ve gone quite early so I don’t know what’s going to happen next. Some people come out of their shells later on in the process, but I would say that, from what I have seen, Lord Sugar does likes Thomas and sees something in him.
What’s next for you?
Too many things. I’m working as a finance manager of the largest retailer in the UK. As well as that, I’ve incorporated my business called Business Decoded, which provides tailored business services to anyone who would like them. I’m also writing my book and I’m juggling being a mother of a two-year-old and a one-year-old.
A critical drug that serves as the backbone of treatment for most childhood cancers, including leukemias, lymphomas and brain tumors, has become increasingly scarce, and doctors are warning that they may soon be forced to consider rationing doses.
Persistent shortages of certain drugs and medical supplies have plagued the United States for years, but physicians say the loss of this medication, vincristine, is uniquely problematic, as there is no appropriate substitute.
“This is truly a nightmare situation,” said Dr. Yoram Unguru, a pediatric oncologist at the Herman and Walter Samuelson Children’s Hospital at Sinai in Baltimore. “Vincristine is our water. It’s our bread and butter. I can’t think of a disease in childhood cancer that doesn’t use vincristine.”
Shortages of the chemotherapy drug, which is on back order, will likely affect children throughout the country, he said, obligating physicians to make difficult decisions.
“There is no substitution for vincristine that can be recommended,” Dr. Unguru said. “You either have to skip a dose or give a lower dose — or beg, borrow or plead.”
Vincristine is one of the drugs used to manage acute lymphoblastic leukemia, the most common childhood cancer. Vincristine is also an important agent in the treatment of Wilms tumor, a rare kidney cancer that mostly affects children.
The Children’s Oncology Group, a collaboration of researchers at hospitals and cancer centers, has made recommendations for altering clinical trial treatment protocols involving vincristine, including checking the hospital pharmacy’s supply before trial enrollment; considering using half the dose if the full amount is not available; skipping doses during the maintenance phase of treatment; or in some cases omitting the drug altogether.
“We are all devastated,” said Dr. Michael Link, a pediatric oncologist at the Stanford University School of Medicine and a former president of the American Society of Clinical Oncology.
Without vincristine, many children with acute lymphoblastic leukemia will still be cured, “but this is a difficult disease to treat in general, and with one hand tied behind your back, it makes it much more difficult,” Dr. Link said.
Since then, Pfizer has been the sole supplier, and the company lately has experienced manufacturing troubles.
“Pfizer has experienced a delay, and we are working closely with them and exploring all options to make sure this critical cancer drug is available for the patients who need it,” the F.D.A. said in a brief statement.
Jessica Smith, a spokeswoman for Pfizer, said the company would expedite additional shipments of the drug over the next few weeks to “support three to four times our typical production output,” in an effort to make up for Teva’s withdrawal from the market.
Teva did not return numerous calls for comment.
The American Society of Health-System Pharmacists tracks more than 200 medications in short supply, among them everyday necessities like antibiotics, dextrose and several vaccines, including the rabies vaccine.
The shortages tend disproportionately to involve older, generic injectable drugs, which are difficult to manufacture but command low prices, a combination that often leads manufacturers to get out of the business of making them.
Those withdrawals may leave just one or two companies continuing to supply the drugs in the United States. Their factories must run at peak production to turn a profit and provide a sufficient supply, but the moment there is a quality problem and production shuts down, shortages follow.
Generic drugs play a vital role in the treatment of cancer. Of the 19,000 American children and adolescents younger than 19 who develop cancer every year, 85 percent are cured. But treatment hinges largely on inexpensive, older drugs like vincristine, which have been off patent for decades.
Shortages cause disruption in treatment. According to a survey published in the New England Journal of Medicine in 2013, 83 percent of oncologists said that they were unable to prescribe the chemotherapy agent they wanted to use because of a shortage, and that they had to substitute a different drug or delay treatment.
Dr. Unguru said the survival rate for acute lymphoblastic leukemia, which accounts for nearly one-quarter of all cancers in children, is nearly 90 percent. But eight of the 10 drugs most commonly used to treat it have been unavailable at times over the past decade.
A drug shortages task force established in 2018 by the former F.D.A. Commissioner Scott Gottlieb is supposed to submit a report with findings and recommendations to Congress by the end of the year.
“This shouldn’t be happening in the United States,” said Dr. Peter Adamson, chair of the Children’s Oncology Group.
“It’s hard enough for any family having a kid with cancer, and having a child with cancer likely to be cured except we can’t give them the drug is beyond the imagination. How can we do that to families?”
Pretzels are the chewy baked treat enjoyed by millions around the globe – and they’re being honoured with their very own Google Doodle.
It comes as Oktoberfest, the world’s largest beer festival, begins on Friday.
The knot-shaped bread is the perfect accompaniment to lager and würstl.
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While in the US a pretzel is often assumed to be a crisp, salted biscuit, in Europe it tends to refer to a fresh, chewy bread.
Thanks to its resemblance to folded arms crossed in prayers, the snack is often credited to monastic bakers. However, it actually originated in Europe prior to the spread of Christianity.
One of the more notable pretzel myths involves a group of monks baking the snacks in a Vienna basement who overheard an invading army tunnelling under the city walls in 1510.
As a reward for helping to thwart the invasion, the pretzel bakers received their own coat of arms.
Indeed, the pretzel has been in use as an emblem of bakers in southern areas of Germany since at least the 12th century.
The unique texture of the pretzel is achieved by dipping the dough in a lye solution and sprinkling with salt just before baking. This results in a chemical process known as the “Maillard reaction”.
While the soft pretzel has existed for centuries, it was only in the nineteenth century that they were baked until hard to extend their shelf life. In 1947, the Reading Pretzel Machinery Company unveiled a pretzel-making machine that produced up to 250 pretzels per minute.
The world’s largest pretzel was baked in 2015 in El Salvador, weighing over 780kg with a length of 29ft.
A cutting-edge cancer treatment can also cure certain kinds of heart failure in mice, scientists reported on Wednesday.
The treatment is a type of immunotherapy known as CAR-T, which has proved life-changing for some patients with blood cancers. CAR-T relies on engineered white blood cells — T cells — that seek out and destroy malignant cells in the body.
In the new study, published in the journal Nature, the technology was used to target scar tissue that stiffens the heart and prevents it from fully relaxing between beats in heart failure patients.
“It is potentially a breakthrough paper,” said Dr. Richard Lee, professor of stem cell and regenerative biology at Harvard who was not involved in the new study.
Medical experts like Dr. Lee agreed that the study is clever and innovative, and at least a proof of principle. But some asked if it would be feasible to use the therapy to treat heart patients, at least in the near future.
For cancer, CAR-T therapy costs about $450,000 per patient. When hospital stays are included, the price can soar to $1 million or more.
There are six million patients in this country with heart failure; even if the treatment at that price were offered to just a few of them, the overall costs would be astronomical.
Some patients getting CAR-T therapy experience severe, even fatal, side effects, including very high fevers, extremely low blood pressure and effects on the brain like confusion or seizures.
Deploying CAR-T against heart failure “is a really clever idea,” said Dr. Douglas Mann, a professor of medicine at Washington University in St. Louis. But given the cost of CAR-T and the side effects, he added, it is not practical today.
In heart failure, the walls of the ventricles, the two large pumping chambers, stiffen and may become enlarged, preventing the heart from pumping blood efficiently through the body. It may result from a number of conditions, including heart attack and high blood pressure.
While many patients respond to drug therapy, those with a type called heart failure with preserved ejection fraction have few treatment options. Half die within five years, a mortality rate comparable to that of some metastatic cancers.
Heart failure is a particular problem for people with muscular dystrophy, Dr. Lee noted. Heart failure, he said, “is a major life-limiting part of the disease.”
Heart muscle stiffens because of scarring, also called fibrosis, said Dr. Jonathan Epstein, lead author of the new study and professor of cardiovascular research at the University of Pennsylvania Perelman School of Medicine.
Fibrosis occurs in a range of other diseases: arthritis, chronic kidney disease and cirrhosis of the liver, for example. It results from the body’s response to inflammation. Although fibrosis is responsible for many of the worst symptoms of these diseases, it’s not clear what effect treating fibrosis might have.
The idea for the study originated with a postdoctoral student in Dr. Epstein’s lab, Haig Aghajanian. He wondered: Why can’t we make a CAR-T therapy to kill scar tissue in the heart?
He knew the way CAR-T works in cancer. T cells of the immune system are constantly scouring the body, looking for rogue cells to attach themselves to and kill. T cells sometimes do not recognize cancer cells, but researchers have found a way to fix that.
They attach a protein to T cells designed to lock on to the cancer. When these engineered T cells drift near a cancer cell, they latch on to it and kill it.
As long as most healthy cells do not have the docking site for that T cell protein, the treatment can work.
“It’s exciting,” said Dr. Elizabeth McNally, a cardiologist and human geneticist at Northwestern University Feinberg School of Medicine. But, she cautioned, there are several potential concerns for any therapy that attacks fibroblasts.
These are cells that help form all tissues, and they play a large role in wound healing. An ideal treatment shouldn’t eliminate fibrosis everywhere, only scars that hinder normal functioning.
So far, Dr. Epstein and his colleagues have not seen problems with wound healing or normal functioning in their animal subjects, but the work is experimental and preliminary.
Dr. Aghajanian and Dr. Epstein began by placing a docking site on scar tissue cells in the hearts of mice with heart failure. Then they made CAR-T cells that lock on to those sites.
Two weeks after the mice were treated, Dr. Aghajanian brought some slides to Dr. Epstein. The two sat side by side peering at them in the microscope. The heart tissue from the mice that were not treated was filled with scars. The heart tissue from the treated mice was clear.
“It was one of those ‘aha’ moments,” Dr. Epstein said. “We looked at each other and did a high-five over the microscope.”
The next step was to look for a naturally occurring protein that is present on human fibrosis cells but not on other cells. The group found one, fibroblast activation protein, or FAP, by looking through a large genetic database.
The scientists learned that mice and other animals also have FAP on scar tissue cells, so they engineered CAR-T cells to seek out the protein. The treatment worked to clear out scar tissue in the mouse hearts, and it did not seem to damage other tissue.
Now the investigators are beginning to repeat the experiment in dogs.