Electronic doctors’ notes could help hospitals plan for surges in COVID-19 cases

A new study, published today in Nature Digital Medicine, found that 'natural language processing' (NLP) of information routinely recorded by doctors – as part of patients' electronic health records – reveal vital trends that could help clinical teams forecast and plan for surges in patients.

The researchers from King's College London, King's College Hospital NHS Foundation Trust (KCH), and Guy's and St Thomas' Hospital NHS Foundation Trust (GSTT), used NLP algorithms to translate the electronic notes made by doctors into a standardized, structured set of medical terms that could be analyzed by a computer.

Tracking trends in patients

In the same way social media posts can be tracked and aggregated by 'hashtags', the researchers detected words or phrases that were 'trending' in electronic health records at KCH and GSTT, during key stages of the COVID-19 pandemic last year. For instance, they tracked the number of patient records containing keywords for symptomatic COVID-19, such as 'dry cough', 'fever' or 'pneumonia'. Throughout the pandemic, hospital doctors have entered patient symptoms and test results into electronic health records, which are used to track the spread of COVID-19 at a national level.

However, these records often contain incomplete and unstructured data, that is difficult to access and analyze.

By analyzing the text as a 'bag of words', the researchers were able to produce real-time maps of trending 'signals' (i.e., symptoms that were most frequently recorded by doctors), and these signals closely mirrored patterns of positive laboratory tests reported by each hospital. Clear spikes were visible in March 2020, for instance, during the first wave of COVID-19 cases, and in subsequent waves.

Providing advance warning for hospitals

The study indicates that these signals provide a real-time situational report of reflecting current activity levels in a hospital and up to four days advance warning for hospitals helping them to prepare for surges in COVID-19 admissions.

The study authors also reported a strong association between the trending signals and regional tracking of COVID-19 admissions in London hospitals. In addition, they found that as new COVID-19 symptoms emerged nationally, these symptoms were also recorded more frequently by doctors at KCH and GSTT.

Dr James Teo, Clinical Director of AI at King's College Hospital and Guy's and St Thomas' Hospital, said: "By teaching computers how to read and understand doctors' notes, we hope to reveal important patterns and trends that could help in the fight against COVID-19 and other diseases.

Tracking word trends in electronic health records offers an additional method for studying disease and healthcare activity, in a way that is very easy and cost-effective to run. While this method was shown to be effective in two individual hospital Trusts, the approach could be scaled up to a regional or even national level with the right privacy safeguards".

CogStack

The CogStack platform used in this study allows researchers to interrogate complex sets of data extremely rapidly, providing a real-time feed of what is happening in a particular hospital, allowing clinical teams to prepare for incoming patients.

The CogStack platform allows us to extract information from deep within hospital records at King's College Hospital NHS Foundation Trust in near real time. This means we can anticipate likely increases in pressure on the system before receiving information such as test results, giving clinical teams time to react and prepare in advance."

Professor Richard Dobson, Head of the Department of Biostatistics & Health Informatics, NIHR Maudsley BRC

Source:

NIHR Maudsley Biomedical Research Centre

Journal reference:

Teo, J.T.H., et al. (2021) Real-time clinician text feeds from electronic health records. npj Digital Medicine. doi.org/10.1038/s41746-021-00406-7.

Posted in: Device / Technology News | Disease/Infection News | Healthcare News

Tags: Artificial Intelligence, Cough, Fever, Healthcare, Hospital, Imaging, Laboratory, Language, Medical Imaging, Medicine, Pandemic, Pneumonia, Research

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Heather Rae Young Hopes Motherhood Softens Pregnant Costar Christine Quinn

A changed woman! Heather Rae Young thinks that becoming a mom will have a major effect on pregnant Christine Quinn’s personality.

Selling Sunset’s Pregnant Christine Quinn Debuts Bare Baby Bump: Photos

“I’m thinking motherhood might soften her a little bit,” the California native, 33, exclusively told Us Weekly on Tuesday, February 23, of her Selling Sunset costar, 32. “From other girls I know in the past, it has softened them. So I’m sure it’ll maybe [happen for her.] I’m hoping it will.”

Young added that while her friendship with the Texas native has “gone up and down” over the years, she did reach out to congratulate Quinn on her pregnancy news. “We had a great little catch-up with each other.”

See Heather Rae Young’s Sweetest Moments With Tarek El Moussa’s 2 Kids

Us confirmed last week that the former model is expecting her first child with husband Christian Richard. “Christine is so excited to be a mother and her friends are so excited for her,” a source exclusively told Us on February 17. She debuted her baby bump that same day on a West Hollywood walk with her dog.

The news came one year after she and the businessman tied the knot. In August 2020, Quinn opened up to Metro about her and Richard’s future family plans.

“I absolutely love kids,” the real estate agent gushed at the time. “I want two. I would love two boys. I can’t even imagine, like, trying to tame a little Christine. I always wanted two little boys just because I’m actually quite a tomboy myself. Obviously, we want to travel first, but then after that we’d love to start a family.”

Quinn first shared photos of her nuptials that same month, writing via Instagram: “Don’t be a Queen waiting for a King. Be a Queen busy with her kingdom until her King arrives.”

She and Young clashed ahead of the ceremony, with Quinn poking fun at her costar’s relationship with Flip or Flop’s Tarek El Moussa at the time.

Ne-Yo, Wife Crystal and More Stars’ 2021 Pregnancy Announcements

Young is still “waiting for that apology,” she told Us on Tuesday. “I’m not one to hold grudges … against someone forever,” she said. “We had a great friendship, and I would like to have at least respect and be able to work together.”

The former actress went on to tell Us that “right now, no,” Quinn is not invited to her and the Flipping 101 With Tarek El Moussa star’s upcoming wedding.

With reporting by Christina Garibaldi

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Critical step forward for radiotherapy with a new method to treat cancer

Critical step forward for radiotherapy with a new method to treat cancer

A new research development from The University of Manchester and the Christie NHS Foundation Trust has shown progress for developing a potential new cancer treatment using high energy electron beams.

The collaborative research team have published their findings in Nature’s journal, Scientific Reports, and demonstrated that Very High Energy Electron (VHEE) beams can have a positive effect for treatment with damage to DNA at similar levels to those conventional X-Rays and proton therapy, whilst harnessing the unique technological qualities of electron beams.

Human cells are composed of DNA and this new result is a fundamental step forward for VHEE radiation as a treatment for a number of cancers. This new treatment has the potential to extend conventional treatment with electron beams used in hospital which only penetrate a few centimeters into the body and struggle to reliably reach deep seated tumors.

This new technology has the potential to extend the toolbox of radiotherapy techniques that can be used in hospitals to treat cancer, in particular an ability to treat deep seated tumors with electrons in a robust manner.

Earlier work from The University of Manchester group indicated this radiation is insensitive to intervening media—meaning if the dimension of the lung changes for example (the patient’s breathing) then the radiation will remain targeted to the tumor, limiting the damage to healthy tissue. The results in this new paper are a first to quantify damage to Double Strands of DNA with high energy electrons.

Following experiments carried out by The University of Manchester, at CERN’s CLEAR 250 MeV facility and at Daresbury Laboratory, the findings show Very High Energy Electron (VHEE) beams are effective at causing DNA damage, important for killing cancer cells, for radiation given over the course of several minutes and for the rapidly evolving field of sub-second FLASH radiation.

In the newly published paper the research group focussed on experimentally determining the DNA Double-Strand Break yield and this was used to evaluate the Relative Biological Effectiveness (RBE)—a key value to evaluate the effectiveness of this type of radiation compared to existing radiation treatments. These results, a first in the field, were found to be consistent with established radiotherapy modalities.

Kristina Small, a Ph.D. student, carried out the experiments, Kristina said: “Electron beam treatment has been identified as a candidate for treatment of lung cancer, a cancer which sadly still has a low survival rate. We have shown, through experiments at CERN and Daresbury Laboratory that VHEEs cause a similar level of damage to DNA compared to protons and X-rays.”

Similarities in physical damage between VHEE and conventional modalities gives confidence that biological effects of VHEE will also be similar—key for clinical implementation. The researchers also made detailed Monte-Carlo (statistically based) simulations—and these complicated simulations were consistent with previous experiments.

Professor Roger Jones from The University of Manchester and Cockcroft Institute said: “This paper represents a significant step in verifying the potential of Very High Energy Electron beams to treat cancer. It relies on a seamless collaboration of The University of Manchester’s Department of Physics and Astronomy, The Division of Cancer Sciences, Daresbury Laboratory and CERN, and The Christie NHS Foundation Trust.

“It is the first to quantify both single strand breaks (SSB) and double strand breakage (DSB) in DNA using VHEE beams. To do this we used plasmids which effectively freeze the damage (as plasmids are not equipped with repair mechanisms that living cells possess) and hence enabled us to process the results obtained at CERN back at the Manchester Cancer Research Centre. These results compare well with detailed Monte Carlo simulations. It also explores the exciting regime of FLASH Radiotherapy—which entails delivering a high dose over a sub-second timescale and where early experiments worldwide show potential to spare healthy cells during treatment. This work points the way for a potential new paradigm in radiotherapy.

“Advantages of this technique over existing methods include—potentially more precise and rapid delivery to tumors with reduced fractionation (number of times the patient has to have a follow up radiation treatment) which result in fewer patient visits needed with a more conformal high dose delivered. Recent results in the area of ultra-high dose rate radiotherapy indicate considerable sparing of healthy tissue.”

The next step is to further demonstrate these exciting results in future experiments. In the long term, researchers hope that VHEE therapy will make a valuable addition to the radiotherapy toolkit in order to improve future cancer treatment.

Dr. Michael Merchant (Division of Cancer Sciences, The University of Manchester) said: “This is an exciting first measurement of DNA damage for very high energy electrons. These measurements will help to build understanding of how to harness the medical applications of very high energy electrons.”

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Is Your State Trying to Ban Transgender Students From Sports? Here's Why That's Wrong

On Monday, Arkansas joined the list of about 20 states who are on the wrong side of progress by trying to ban transgender children from sports. Introduced by Arkansas Attorney General Leslie Rutledge, Republican Sen. Missy Irvin, and Rep. DeAnn Vaught, the legislation would prohibit transgender athletes from playing on girls’ and women’s sports teams at schools, the Associated Press reports.

The Human Rights Campaign is currently tracking these bills in states from Montana to Mississippi and from Connecticut to North Dakota, with information on what you can do to help stop them from becoming discriminatory laws. (The only state so far to pass one of these bills has been Idaho, which quickly had the law suspended by a district court.)

This flurry of transphobic legislation is a knee-jerk, unnecessary, and discriminatory reaction to President Joe Biden’s executive order preventing and combating discrimination on the basis of gender identity or sexual orientation. Signed on his first day in office, this executive order calls for a broader application of last year’s Supreme Court Bostock v. Clayton County ruling, which mandated that LGBTQ people are protected from sex discrimination in the workplace, and calls for the Supreme Court ruling to apply to Title IX, the federal law that prohibits discrimination in federally funded schools.

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“Every person should be treated with respect and dignity and should be able to live without fear, no matter who they are or whom they love,” Biden’s executive order reads. “Children should be able to learn without worrying about whether they will be denied access to the restroom, the locker room, or school sports.”

Sounds totally reasonable to us, but apparently not to transphobic people.

“We don’t want common sense to be overshadowed by so-called political correctness, and this bill will ensure the integrity of girls and women in sports,” AG Rutledge said of her state’s proposed legislation at a news conference at the state capitol, though she acknowledged she isn’t aware of any instances in Arkansas of transgender athletes playing on school sports teams.

These proposed bills are, frankly, absurd. First, Biden’s executive order didn’t change anything. LGBTQIA people are already protected under federal law, and this executive order simply reiterates that and directs that those protections be enforced. Second, there is literally no evidence of any kind that protecting the rights of transgendered athletes to play on teams consistent with their gender identities does any harm to cis-gendered athletes. The “integrity of girls and women in sports” is not at risk.

As transgender rights activist Chase Strangio, a staff lawyer with the ACLU, recently expressed in an article on Medium, “Behind the past two years of anti-trans rhetoric and policy in the United States is the false claim that women and girls who are transgender are a threat to the integrity of women’s sports,” Strangio wrote. “Though they can point to only a handful of trans athletes who have had any success in sport over the past four decades, they claim that trans dominance in sport is ‘just around the corner.’ Notably, trans women have been competing in women’s events at the NCAA, the Olympics, and elite international competition without any dominance or even notable competitiveness. In fact, no trans woman athlete has even qualified for the Olympics let alone won a medal.”

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The truth is that these hateful laws would be far, far more harmful to transgendered kids than to female athletes. Not affirming trans and gender-expansive kids in who they are, or preventing them from living lives as full and free as anyone else only results in serious damage to their mental health, leading to devastating rates of suicide. According to a study of non-binary youth published by the American Academy of Pediatrics, 41.8 percent of respondents stated that they had attempted suicide at some point in their lives. That is a heartbreaking statistic.

“Relentless scrutiny of trans youth is hurting them deeply,” Strangio wrote on Medium. “They participate in sports because they love them and want to find a place to connect, feel joy and experience embodiment. … No one is protected when trans youth are demonized, when they are kicked off the sports teams they love and their health care is criminalized. There is no trans takeover of sports waiting around the corner, but how many young people will cry out, ‘I have no happiness left in me’ while we perpetuate this false claim?

We as parents and as humans must do better to protect, nurture and encourage all kids. It shouldn’t matter what gender they identity with, or what pronoun they use. All children deserve the opportunity to exist exactly as they are, to learn at school and play on sports teams, and do whatever nourishes their hearts and souls. This is what we should be teaching our children, that accepting other people is more important than protecting some false idea that letting trans kids play sports will mean our team wins less trophies. When we are inclusive, we all win something much bigger.

Read about Braunwyn Windham-Burke and other lesbian, bisexual, gay and queer celebrity parents we love.

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Most women receive inappropriate treatment for urinary tract infections

antibiotic

Nearly half of women with uncomplicated urinary tract infections received the wrong antibiotics and almost three-quarters received prescriptions for longer than necessary, with inappropriately long treatment durations more common in rural areas, according to a study of private insurance claims data published today in Infection Control & Hospital Epidemiology, the journal of the Society for Healthcare Epidemiology of America.

“Inappropriate antibiotic prescriptions for uncomplicated urinary tract infections are prevalent and come with serious patient- and society-level consequences,” said Anne Mobley Butler, Ph.D., lead author of the study and assistant professor of medicine and surgery at Washington University School of Medicine, St. Louis. “Our study findings underscore the need for antimicrobial stewardship interventions to improve outpatient antibiotic prescribing, particularly in rural settings.”

Researchers studied insurance claims data for 670,400 women ages 18 to 44 who received an outpatient diagnosis of uncomplicated urinary tract infection between April 2011 and June 2015. They identified filled antibiotic prescriptions, assessed adherence to clinical guidelines, and compared rural and urban antibiotic usage patterns.

Rural patients were more likely to receive a prescription for an inappropriately long duration of therapy than urban patients, according to an analysis of geographic data from the claims database. While use of both inappropriate antibiotic choice and inappropriate duration of prescriptions declined slightly over the study period, inappropriate prescriptions continued to be common with 47% of prescriptions written for antibiotics outside guideline recommendations and 76% for an inappropriate duration, nearly all of which were longer than recommended.

“Accumulating evidence suggests that patients have better outcomes when we change prescribing from broad-acting to narrow-spectrum antibiotics and from longer to shorter durations,” Butler said. “Promoting optimal antimicrobial use benefits the patient and society by preventing avoidable adverse events, microbiome disruption, and antibiotic-resistant infections.”

Clinicians should periodically review clinical practice guidelines, even for common conditions, to determine the ideal antibiotic and treatment duration, Butler said. Auditing outpatient antibiotic prescribing patterns and periodic feedback to healthcare provider helps remind clinicians of the best practices and improves antibiotic prescribing. However, additional research should be performed to understand and ultimately improve rural outpatient antibiotic prescribing practices for urinary tract infections and other common conditions.

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Stormi Webster Perceives Things so Differently Now, According to Dad Travis Scott

As a musician always looking for a new sound, Travis Scott has found a tiny muse in Stormi Webster, his daughter with Kylie Jenner. “Fatherhood influences my job,” Scott told director Robert Rodriguez in a recent interview in I-D magazine. “It has a huge impact. It’s a major inspiration, you know what I’m saying?”

Though Stormi just celebrated her third birthday, Scott said he can already see how his daughter perceives things so differently than he did as a kid.

“It’s so crazy, Stormi’s generation is way different from mine, and she’s way different from my younger brother and sister,” he said in the interview. “Kids show you a different outlook on life, how they view things, the type of pressures they have and what makes them happy, what makes them move. Like, when she watches certain movies or listen to certain songs. Or she watches my concerts on YouTube and she realizes she’s there, she’s ready to see now.”

It’s really cool to see a little girl through an artist dad’s eyes like that. Scott has previously talked about how he and ex Jenner are co-parenting Stormi to grow into a strong woman who has the “knowledge of just how to carry yourself, how to move in this world, how to be strong, how to not even be scared to take that risk on any idea, jump out on any activity.” Yasssssss, feminist dad!

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Being dad to Stormi also helped Scott better understand how he is a role model for kids and the effect he can have on the younger generation. “I realized my job is way more important than what I thought because of her,” he said. “More responsibility, you know? You’ve got to use that properly.”

Becoming a parent really does change one’s perspective on, well, just about everything, right? And at only age 28, Scott is such a relatively young dad that he has plenty of time to use his music career and celebrity to be a positive influence on Stormi’s generation as well as several generations to come. (Stormi’s generation is called Generation Alpha, in case you were wondering, and includes babies born between 2011 and 2025.)

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Scott is releasing his much anticipated fourth studio album titled Utopia, sometime this year, and he said being Stormi’s dad has affected his attitude toward both his personal life and his career. “Fatherhood just be like, I don’t live for myself anymore,” Scott said in the I-D interview. “I was already going so hard for the fans and now, oh man, Stormi, it’s like… I love that.”

Aw, devoted dads like Scott are just the best!

Read about how celebrity parents talk to their kids about racism.

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New vaccine needed for serious childhood pneumonia

New vaccine needed for serious childhood pneumonia

A UNSW Sydney-led medical research team has called for a new vaccine, improved strategies and enhanced monitoring to combat serious complications from childhood pneumonia.

The researchers examined the impact of the 13-valent pneumococcal conjugate vaccine (13vPCV) on childhood pneumonia and empyema—complicated pneumonia—after its introduction to the Australian National Immunisation Program about a decade ago.

The new study, published in Thorax recently, found that while 13vPCV resulted in a 21% decrease in childhood pneumonia hospitalisations, there was a contemporaneous 25% increase in admissions for empyema.

This incidence data for childhood empyema hospitalisations is similar to that reported in other countries.

Approximately 7,000 Australians under the age of 18 are hospitalized with pneumonia each year.

Senior author Professor Adam Jaffe, Head of the School of Women’s and Children’s Health at UNSW Medicine & Health, said the researchers’ findings suggested an emergence of non-vaccine serotypes—those which 13vPCV does not cover.

13vPCV was introduced to cover the 13 most common serotypes responsible for invasive pneumococcal infection, extending coverage to six additional serotypes including 1 and 3.

The previous vaccine (7vPCV) covered seven serotypes. A serotype is a distinct variation within a bacteria species.

Prof. Jaffe said: “Although we found a substantial reduction in serotype 1, serotype 3 is now the predominant organism which causes childhood empyema—in 76% of cases—so, efforts must be made to create a vaccine which is more effective against serotype 3.

“In fact, Australia recently changed the vaccination dosage schedule to try and improve the effectiveness of 13vPCV against serotype 3, but we need to continue monitoring patients using molecular techniques to see if this change has had an impact.

“Childhood bacterial pneumonia and empyema are potentially preventable diseases through vaccination. So, if Australia can develop an effective vaccine, we could prevent children from being hospitalized with pneumonia and empyema.”

Empyema is infected fluid around the lungs and about 1% of children hospitalized with pneumonia develop it.

Although children are highly unlikely to die from empyema, they can expect a long stay in hospital for treatment with antibiotics and surgery, or the insertion of a drain. If adults develop empyema, about a third are likely to die.

Continuing enhanced surveillance needed

The researchers conducted a similar study during the period of the superseded 7vPCV. Their new study—which took four years to complete—is part of a broader research project on 13vPCV.

“Our new study had two parts,” Prof. Jaffe said. “We analyzed national hospitalisations for childhood empyema and childhood pneumonia, then we conducted an enhanced surveillance study on children with empyema.”

The first part of the research used publicly available hospitalisations data—about 36,000 admissions—to assess whether the introduction of 13vPCV changed how many children were admitted to hospital with pneumonia and empyema.

The enhanced surveillance study involved the collection of blood and lung fluid samples from 401 children with empyema from February 2015 to September 2018.

The children were receiving treatment in 11 major children’s hospitals across Australia.

Most children were boys (208 or 52%) and the median age was four years old.

The researchers then conducted molecular testing on these samples and compared the results to their previous study undertaken during the period of 7vPCV.

The multidisciplinary team included Dr. Nusrat Homaira, of the Discipline of Paediatrics at UNSW Medicine & Health, and pediatric research nurse Roxanne Strachan of Sydney Children’s Hospital.

Prof. Jaffe said: “Our new research is the first of its kind in Australia—so, we now have the best data available for complicated childhood pneumonia to help guide future vaccination introductions and improve vaccine strategies.

“We are currently working on our larger study, of which this was a subset, to examine the effectiveness of 13vPCV on children with bacterial pneumonia. We will need to repeat the study in a few years’ time to help with monitoring.

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Seeing schizophrenia: X-rays shed light on neural differences, point toward treatment

Seeing schizophrenia: X-rays shed light on neural differences, point toward treatment

Schizophrenia, a chronic, neurological brain disorder, affects millions of people around the world. It causes a fracture between a person’s thoughts, feelings and behavior. Symptoms include delusions, hallucinations, difficulty processing thoughts and an overall lack of motivation. Schizophrenia patients have a higher suicide rate and more health problems than the general population, and a lower life expectancy.

There is no cure for schizophrenia, but the key to treating it more effectively is to better understand how it arises. And that, according to Ryuta Mizutani, professor of applied biochemistry at Tokai University in Japan, means studying the structure of brain tissue. Specifically, it means comparing the brain tissues of schizophrenia patients with those of people in good mental health, to see the differences as clearly as possible.

“The current treatment for schizophrenia is based on many hypotheses we don’t know how to confirm,” Mizutani said. “The first step is to analyze the brain and see how it is constituted differently.”

To do that, Mizutani and his colleagues from several international institutions collected eight small samples of brain tissue—four from healthy brains and four from those of schizophrenia patients, all collected post-mortem—and brought them to beamline 32-ID of the Advanced Photon Source (APS), a U.S. Department of Energy (DOE) Office of Science User Facility at DOE’s Argonne National Laboratory.

At the APS, the team used powerful X-rays and high-resolution optics to capture three-dimensional images of those tissues. (Researchers collected similar images at the Super Photon Ring 8-GeV [SPring-8] light source facility in Japan.) The resolution of the X-ray optics used at the APS can be as high as 10 nanometers. That’s about 700 times smaller than the width of the average red blood cell, and there are five million of those cells in a drop of blood.

“There are only a few places in the world where you can do this research,” Mizutani said. “Without 3-D analysis of brain tissues this work would not be possible.”

According to Vincent De Andrade, physicist in Argonne’s X-ray Science Division, capturing images at high resolution presents a challenge, since the neurons being imaged can be centimeters long. The neuron is the basic working unit of the brain, a cell within the nervous system that transmits information to other cells to control body functions. The human brain has roughly 100 billion of these neurons, in various sizes and shapes.

“The sample has to move through the X-ray beam to trace the neurons through the sample,” De Andrade explained. “The field of view of our X-ray microscope is about 50 microns, about the width of a human hair, and you need to follow these neurons over several millimeters.”

What these images showed is that the structures of these neurons are uniquely different in each schizophrenia patient, which Mizutani said is evidence that the disease is associated with those structures. Images of healthy neurons were relatively similar, while neurons from schizophrenia patients showed far more deviation, both from the healthy brains and from each other.

More study is needed, Mizutani said, to figure out exactly how the structures of neurons are related to the onset of the disease and to devise a treatment that can alleviate the effects of schizophrenia. As X-ray technology continues to improve—the APS, for example, is scheduled to undergo a massive upgrade that will increase its brightness up to 500 times—so will the possibilities for neuroscientists.

“The APS upgrade will allow for better sensitivity and resolution for imaging, making the process of mapping neurons in the brain faster and more precise,” De Andrade said. “We would need resolutions of better than 10 nanometers to capture synaptic connections, which is the holy grail for a comprehensive mapping of neurons, and those should be achievable with the upgrade.”

De Andrade also noted that while electron microscopy has been used to map the brains of small animals—fruit flies, for instance—that technique would take a long time to image the brain of a larger animal, such as a mouse, let alone a full human brain. Ultrabright, high energy X-rays like those at the APS, he said, could speed up the process, and advances in technology will help scientists get a more complete picture of brain tissue.

For neuroscientists like Mizutani, the end goal is fewer people suffering with brain diseases like schizophrenia.

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He's Here! Mandy Moore and Husband Taylor Goldsmith Welcome Son August Harrison: 'Our Sweet Boy'

Mandy Moore is a mom!

The This Is Us actress, 36, and her husband Taylor Goldsmith have welcomed their first child together, son August Harrison Goldsmith, she announced on Instagram Tuesday.

"Gus is here 💙💙💙💙. Our sweet boy, August Harrison Goldsmith. He was punctual and arrived right on his due date, much to the delight of his parents," she wrote in her caption. "We were prepared to fall in love in all sorts of brand new ways, but it goes beyond anything we could have ever imagined."

Moore's baby announcement comes weeks after she revealed that her birth plan had to be altered. "My platelets have dropped exponentially during pregnancy and it's sadly altered my birth 'plan,' " she wrote on Instagram in early February.

Moore, who announced she was expecting back in September, has been open about her difficult first trimester and fertility struggles. In a Janurary interview with Romper, the singer said she was "very hesitant" to believe she was pregnant because of past issues with her uterus.

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 See Pregnant Mandy Moore's Sweetest Baby Bump Photos

"I sort of was holding my breath until 12 weeks," she said at the time, adding that in her third trimester, she had an "it's real" moment: "The little things kind of get me. Like, I was online buying pacifiers yesterday and I just turned to my husband and I was like, It's real. There's going to be a little human that needs a pacifier."

During her pregnancy, Moore opened up to her fans about suffering a loss: her pet dog Joni. On Dec. 1, she shared the heartbreaking news on Instagram, writing that her "heart is utterly shattered" in the wake of the canine's death. "She was my first love and best friend. Through every twist and turn of life of this past decade and change, she was right there."

"She was the boss and a total mama's girl," she added of Joni. "I'm so sad she won't get the chance to meet her human brother soon but maybe she wasn't ready to share 😉."

Celebrity Babies Born in 2021 (So Far!)

Then, in January, Goldsmith surprised her with a sentimental gift as they grieved the pet's death. She shared photos on Instagram of a toy dog from Cuddle Clones that is a near-perfect replica of her late pup. "This was by far my fav gift over the holidays- something that @taylordawesgoldsmith had made. It's a little stuffed animal version of my beloved Joni so that our son will still know her, even though they never got to meet."

In a recent episode of Informed Pregnancy Podcast, Moore told host Dr. Elliot Berlin that she is open to having more children soon.

"I have such a deeper appreciation for my body and the fact that us pregnant folks have the capability to do this. It's the coolest thing," she said. "I mean, I know that I joke with my husband already. We're not at the end of the rollercoaster ride yet, and like, I'll do this again. I'm so ready to do this again. Even if I was as sick as I was during the first trimester, there is something I think in the third trimester that is so profoundly magical and beautiful."

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After billions of dollars and dozens of wartime declarations, why are vaccines still in short supply?

The U.S. government has invested billions of dollars in manufacturing, used a wartime act dozens of times to boost supplies and yet there's still not enough covid vaccine on the way to meet demand — or even the government's own goals for national immunization.

President Joe Biden, in remarks at the National Institutes of Health this month, said the nation is "now on track to have enough supply for 300 million Americans by the end of July." But at the current rate of production, Pfizer and Moderna will miss their targets of providing at least 100 million doses each by the end of March, let alone 200 million more doses each has promised by July.

Moderna would need to more than double its vaccine production rate from January — when it made roughly 19 million doses — to meet its contractual obligations. Pfizer supplied 40 million vaccine doses by Feb. 17. It has roughly six weeks left to deliver the first 120 million doses it has promised.

Biden and officials from the two companies say they are rapidly expanding production capacity. But critics are lining up. They want to know whether the government did enough, fast enough, to guarantee that companies would meet the urgent challenges of the pandemic. As for the manufacturers bolstered by extraordinary sums of taxpayer money, why did they not share technology and know-how sooner, or move more quickly into strategic production partnerships?

Experts say it's complicated, noting that the output of raw materials and assembly lines can't be ratcheted up 10,000-fold at the push of a button — and that the effort thus far has been close to miraculous. They cite bottlenecks in at least three areas: the production of specialty lipids, fatty materials that are a primary component of the Moderna and Pfizer-BioNTech vaccines; the hundreds of millions of glass vials that hold the vaccine; and the sterile automated assembly lines where vaccine moves from bulk containers into vials before shipment.

U.S. officials have run headlong into the limits of the Defense Production Act, a Korean War-era law that allows the federal government to ramp up supplies of critical materials in times of national emergency. The vaccine manufacturing process relies on a complex supply chain, from sourcing raw materials and equipment to designing chemical processes, building production lines and hiring and training workers.

Also, experts note, no one knew which vaccines would prove effective.

"A year ago there was no commercial market for mRNA product. There was scientific research and pharma making small-volume clinical lots. Now we need billions of doses, in the space of a year. That's overloading the supply infrastructure," said Kevin Gilligan, a senior consultant with Biologics Consulting and a former official with the Biomedical Advanced Research and Development Authority, or BARDA, a federal agency created in 2006 to deal with pandemics and bioterrorism.

As of December, the Trump administration through its Operation Warp Speed initiative had obligated nearly $14 billion for vaccine development and manufacturing, including investments to expand U.S. capacity, according to a Government Accountability Office report in January. The administration invoked the Defense Production Act on at least 23 vaccine-related contracts, in part to prioritize the government's contracts over others, according to a KHN review of the federal contracts database, contracts obtained by the nonprofit group Knowledge Ecology International, GAO and government news releases.

They include the December contract that the Department of Health and Human Services signed with Pfizer for another 100 million doses, on top of the initial 100 million it committed to last summer. That contract, worth $1.95 billion, included DPA provisions to give the company priority access to raw materials and spare parts for factories, according to a former administration official.

The DPA has also been used in vaccine contracts with Moderna, Johnson & Johnson and other drug companies for hundreds of millions of doses. On top of that, the law has been invoked for at least 10 contracts with companies making needles or syringes. It's been used to require glass makers Corning and SiO2 Materials Science to prioritize vial production for vaccine production, and in contracts for aspects of manufacturing with companies like Emergent BioSolutions, Fujifilm Diosynth Biotechnologies and Grand River Aseptic Manufacturing.

Operation Warp Speed awarded Emergent BioSolutions $648 million last year to boost the manufacturing capacity it needed to enter agreements with Johnson & Johnson and AstraZeneca — worth at least $615 million and $261 million, respectively — to help make their vaccines. Grand River Aseptic Manufacturing won a $160 million award from BARDA and has contracted with Johnson & Johnson to fill vials and finish packaging of its single-shot covid vaccine, which is expected to get emergency authorization from the Food and Drug Administration as soon as this month but will only have a few million doses available initially.

The Biden administration has expanded its use of the wartime act to prioritize equipment like filling pumps and filtration systems for Pfizer. "We told you that when we heard of a bottleneck on needed equipment, supplies or technology related to vaccine supply, that we would step in and help," Tim Manning, the White House official leading the administration's covid supply efforts, said during a February press briefing.

Yet it can do only so much, according to medical supply chain experts. Prashant Yadav, a senior fellow at the Center for Global Development at Harvard University, said it could take months for the impact of that DPA action to be felt because of the time it takes to procure equipment and get it installed, with each step tightly regulated.

The U.S. is unlikely to get a meaningful bump in capacity "unless we think about co-production deals," in which a drug company agrees to manufacture a competitor's vaccine, said Tinglong Dai, an associate professor at Johns Hopkins University's Carey Business School.

So far, such arrangements have proliferated in Europe — which has less capacity to produce drugs than the United States does. Deals with other major vaccine manufacturers have been less common on the U.S. side of the pond.

"Though we have not partnered with, say, another large pharma for production, we have built strategic partnerships with a number of organizations that have been instrumental to our scaling up and meeting supply and commercialization plans," Moderna spokesperson Ray Jordan said in an email.

Moderna this month said that its manufacturing process would scale up rapidly in the coming weeks, that it would provide the U.S. between 30 million and 35 million doses in February and March and between 40 million and 50 million doses monthly from April to July. The company declined to elaborate on what made the boost possible.

Vaccine manufacturers long ago should have been sharing technology and expertise to boost production in the U.S. and Europe, and especially in developing countries, said James Love, director of Knowledge Ecology International, a nonprofit focused on patent rights.

"We've wasted about a year by not doing some of the obvious things," he said. "The rhetoric is that it's an emergency. But on the scale-up of manufacturing, you just don't see it."

It's not that simple, others say. "There wasn't any excess capacity available in the United States a year ago. Zero," Paul Mango, a former HHS official heavily involved in Operation Warp Speed, said regarding vaccines. "It's getting the equipment. It's quality control. It's getting the employees. People make it sound like this is easy. You can't just push 400 workers and say, go at it."

Each Pfizer-BioNTech or Moderna shot contains billions of lipid nanoparticles, each particle containing four lipids and a strand of the nucleic acid RNA, the five pieces assembled in a way that allows the RNA to enter our cells and create a particle that stimulates the immune system to defend against the covid virus.

The lipids, which are made only in a handful of factories, have been a major supply problem. "No one has ever thought of a scenario where we would use lipid nanoparticle formulation for [billions of] doses," Yadav said. "We have not invented a process for doing lipid nanoparticles at scale."

Two of the lipids in the vaccine, cholesterol and DSCP, have long been used in industry to shape and buffer chemical formulations. A third lipid prevents the particles from clumping together. A fourth enables the lipid shell of the vaccine to fuse with human cells and, once inside the cell, to crack open so the RNA can move to a structure called a ribosome and make proteins that stimulate immunity.

All of these raw materials are produced under regulated conditions — in Massachusetts, Missouri, Colorado and Alabama by companies under license with Moderna, Pfizer or Acuitas Therapeutics, which was co-founded by Pieter Cullis, a University of British Columbia professor who is considered the grandfather of lipid nanoparticle technology.

Before the pandemic, these companies produced meager amounts for use in small clinical trials, laboratory experiments or in one licensed drug, patisiran, which is used to treat a rare genetic disease in about a thousand people worldwide. Now they are producing thousands of kilograms of the stuff, said Stefan Randl, a vice president at Evonik, a lipid maker. Evonik recently announced it would scale up production at two German sites, possibly in the second half of the year, to be used in the Pfizer-BioNTech vaccine. The company last year bought a U.S. lipid manufacturer in Alabama.

"All of a sudden the quantities had to be ramped up a thousand-fold or more," Randl said. "This is the biggest bottleneck."

Several elements of the vaccine, including lipids and enzymes used in making the mRNA, until recently were produced using animal products such as sheep's wool, said Andrew Geall, chief scientific officer at Precision NanoSystems, which designs equipment for mixing the mRNA and lipids. Animal products could cause contamination or disease, even in minute quantities, so manufacturers now use synthetic chemicals.

Luckily, the cosmetic industry — a major user of some of the same lipids used in the vaccines — has been switching from animal products in recent decades, noted Julia Born, an Evonik spokesperson.

Still, only a limited number of companies globally have expertise and facilities to make the lipids, said Thomas Madden, CEO and a co-founder of Acuitas, and they've all struggled to move from quantities produced in a laboratory to industrial-scale production. For instance, he said, hazardous solvents and chemicals used in laboratory procedures need to be avoided in industrial processes, where they could give rise to workplace safety issues.

"This is a hugely complex supply chain," Madden said. "Once you address a bottleneck at one point, you identify the next bottleneck in the process. It's a bit of a game of whack-a-mole."

Although it's not particularly difficult to make the lipids used in vaccines, it takes time to get FDA authorization of a facility that can make them in high quantities, said Cullis, the UBC professor. It would take two to three years to start such a factory from scratch, so instead, Moderna and Pfizer-BioNTech have been hooking up with existing manufacturers and getting them to convert to lipid production, he said.

Another bottleneck is "fill/finish" — getting the finished vaccine into vials or syringes so the shots can be shipped to customers. Vaccine filling lines require extremely high levels of efficiency and sterility, and few companies in the world have this capacity, said Mike Watson, former president of Valera, a Moderna subsidiary. Moderna has hired Catalent, a contract manufacturer that recently experienced delays that slowed the release of some doses, to fill and finish U.S. doses at its facility in Bloomington, Indiana. At least two other companies will do the same for Moderna's vaccine supply abroad.

In January, the French multinational Sanofi — whose own covid vaccine has been delayed by poor performance in producing immunity — agreed to offer its fill/finish line in Germany for the Pfizer-BioNTech vaccine. That line isn't expected to be running until July.

In the U.S., the number of vaccine doses shipped to states has ticked up in recent weeks, partly because Pfizer said its five-dose vials actually provide six shots. Moderna is seeking FDA permission to add up to five doses to its 10-dose vials.

Pfizer has said it is manufacturing raw materials in St. Louis, the active ingredients for the vaccine in Andover, Massachusetts, and filling vials in Kalamazoo, Michigan.

CEO Albert Bourla, with Biden at his side in Kalamazoo on Friday, said the company added lipid production capabilities at plants in Michigan and Connecticut, as well as fill/finish lines in Kansas. He said it has significantly cut the average time it takes to make doses — from 110 days to 60 days.

"Today, during this meeting, the president challenged us to identify additional ways in which his administration could help us potentially accelerate even further the delivery of the full 300 million doses earlier than July," Bourla said. "The challenge is accepted, and we will try to do our best."

This story was produced by KHN, which publishes California Healthline, an editorially independent service of the California Health Care Foundation.

This article was reprinted from khn.org with permission from the Henry J. Kaiser Family Foundation. Kaiser Health News, an editorially independent news service, is a program of the Kaiser Family Foundation, a nonpartisan health care policy research organization unaffiliated with Kaiser Permanente.

Posted in: Healthcare News

Tags: Cell, Cholesterol, Contamination, Coronavirus, Drugs, Genetic, Health and Human Services, Health Care, Immune System, Immunization, Laboratory, Lipids, Manufacturing, Mole, Nanoparticle, Nanoparticles, Nucleic Acid, Pandemic, Pharmaceuticals, Public Health, Research, Ribosome, RNA, Running, Therapeutics, Vaccine, Virus

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