Did you make a New Year’s resolution to exercise more? And perhaps the more important question: Will you stick to your goal?
These questions are especially important for older adults, who are at a higher risk for chronic diseases such as dementia, cardiovascular disease, depression and anxiety. Physical activity can help reduce the risk for many of these conditions.
“We need to start thinking about these diseases [as diseases] of neglect, not necessarily of aging, that occur because people have not been able to maintain a lifelong pattern of healthy behavior,” said Randall Stafford, MD, PhD, a professor of medicine, in an article originally reported by Stanford’s BeWell.
Evolving intensity
Stafford explained that the exercises appropriate for any one person will likely evolve over his or her lifetime, but increasing physical activity at any age can quickly improve health.
Take my 92-year old relative Al, for instance. He started training and running marathons when he turned 40. In his 80s, he stopped running based on his doctor’s advice but kept hiking. These days, he walks a mile or rides his exercise bike for 30 minutes at a slow pace with breaks, along with strength and training exercises. His goal: Live an active, independent life.
But even if you’re not like Al (yet), it’s not too late; exercise doesn’t have to be something as intense as running a marathon.
“Even incorporating a few minutes of walking into one’s daily routine can be quite beneficial,” said Stafford. “Physical activity has benefits that are immediate as well as sustained.” And people often become better or more comfortable doing physical activities with practice, he said.
Expanding your mindset
Stafford’s other good news? You don’t have to do vigorous, gym-based exercises; joyful movements like gardening or dancing count. You’ll also get an extra social benefit if you share these physical activities with friends or family members, plus you are more likely to stick with the healthy behavior if you do it with others.
Stafford, however, stressed the importance of including strength training, core exercises and stretching — especially for people over 40 — to reduce muscle loss, maintain balance and stay flexible.
Finally, Stafford advised not to beat yourself up if you slide back into sedentary habits. Setbacks happen. Just try to get back into a routine as soon as you’re able.
This is a reposting of my Scope blog story, courtesy of Stanford School of Medicine.
An animation shows how charging and discharging a lithium battery test cell causes an island of “dead,” or detached, lithium metal to creep back and forth between the electrodes. The movement of lithium ions back and forth through the electrolyte creates areas of negative (blue) and positive (red) charge at the ends of the island, which swap places as the battery charges and discharges. Lithium metal accumulates at the negative end of the island and dissolves at the positive end; this continual growth and dissolution causes the back-and-forth movement seen here. SLAC and Stanford researchers discovered that adding a brief, high-current discharging step right after charging the battery nudges the island to grow in the direction of the anode, or negative electrode. Reconnecting with the anode brings the island’s dead lithium back to life and increases the battery’s lifetime by nearly 30%. (Greg Stewart/SLAC National Accelerator Laboratory.)
Menlo Park, Calif. — Researchers at the Department of Energy’s SLAC National Accelerator Laboratory and Stanford University may have found a way to revitalize rechargeable lithium batteries, potentially boosting the range of electric vehicles and battery life in next-gen electronic devices.
As lithium batteries cycle, they accumulate little islands of inactive lithium that are cut off from the electrodes, decreasing the battery’s capacity to store charge. But the research team discovered that they could make this “dead” lithium creep like a worm toward one of the electrodes until it reconnects, partially reversing the unwanted process.
Adding this extra step slowed the degradation of their test battery and increased its lifetime by nearly 30%.
“We are now exploring the potential recovery of lost capacity in lithium-ion batteries using an extremely fast discharging step,” said Stanford postdoctoral fellow Fang Liu, the lead author of a study published Dec. 22 in Nature.
Lost connection
A great deal of research is looking for ways to make rechargeable batteries with lighter weight, longer lifetimes, improved safety, and faster charging speeds than the lithium-ion technology currently used in cellphones, laptops and electric vehicles. A particular focus is on developing lithium-metal batteries, which could store more energy per volume or weight. For example, in electric cars, these next-generation batteries could increase the mileage per charge and possibly take up less trunk space.
Both battery types use positively charged lithium ions that shuttle back and forth between the electrodes. Over time, some of the metallic lithium becomes electrochemically inactive, forming isolated islands of lithium that no longer connect with the electrodes. This results in a loss of capacity and is a particular problem for lithium-metal technology and for the fast charging of lithium-ion batteries.
However, in the new study, the researchers demonstrated that they could mobilize and recover the isolated lithium to extend battery life.
“I always thought of isolated lithium as bad, since it causes batteries to decay and even catch on fire,” said Yi Cui, a professor at Stanford and SLAC and investigator with the Stanford Institute for Materials and Energy Research (SIMES) who led the research. “But we have discovered how to electrically reconnect this ‘dead’ lithium with the negative electrode to reactivate it.”
Creeping, not dead
The idea for the study was born when Cui speculated that applying a voltage to a battery’s cathode and anode could make an isolated island of lithium physically move between the electrodes – a process his team has now confirmed with their experiments.
The scientists fabricated an optical cell with a lithium-nickel-manganese-cobalt-oxide (NMC) cathode, a lithium anode and an isolated lithium island in between. This test device allowed them to track in real time what happens inside a battery when in use.
They discovered that the isolated lithium island wasn’t “dead” at all but responded to battery operations. When charging the cell, the island slowly moved towards the cathode; when discharging, it crept in the opposite direction.
“It’s like a very slow worm that inches its head forward and pulls its tail in to move nanometer by nanometer,” Cui said. “In this case, it transports by dissolving away on one end and depositing material to the other end. If we can keep the lithium worm moving, it will eventually touch the anode and reestablish the electrical connection.”
Boosting lifetime
The results, which the scientists validated with other test batteries and through computer simulations, also demonstrate how isolated lithium could be recovered in a real battery by modifying the charging protocol.
“We found that we can move the detached lithium toward the anode during discharging, and these motions are faster under higher currents,” said Liu. “So we added a fast, high-current discharging step right after the battery charges, which moved the isolated lithium far enough to reconnect it with the anode. This reactivates the lithium so it can participate in the life of the battery.”
She added, “Our findings also have wide implications for the design and development of more robust lithium-metal batteries.”
This work was funded by the DOE Office of Energy Efficiency and Renewable Energy, Office of Vehicle Technologies under the Battery Materials Research (BMR), Battery 500 Consortium and eXtreme Fast Charge Cell Evaluation of Li-ion batteries (XCEL) programs.
This is a reposting of a press release, courtesy of SLAC National Accelerator Laboratory.
Alaina Levine loves being a professional speaker and coach. As she moderated the virtual ScienceWriters2021 session “Professional (Paid) Speaking: Building a Sustainable Revenue Stream,” her energy radiated through the screen. Her panelists were also “in awe of her energy,” and one asked what she had for breakfast. “Three cups of coffee, four tacos and two cupcakes,” Levine replied. Is this the new breakfast of champions?
Levine’s session focused on how to leverage science writing expertise into paid speaking engagements. The panel included three multi-talented science journalists who are professional speakers.
After introductions, Levine polled the audience to ascertain their speaking expertise. For example, one question asked “What is the highest you have been paid for a speaking engagement?” The majority of the attendees admitted, “I can get PAID??”
The panelists then offered insights and practical tips to their inexperienced audience. First, they explained how they choose their speaking topics and the kinds of engagements they do. As one might expect, their programs are largely guided by their science writing beats. And their engagements are various, including TedX talks, keynotes, panels and trainings.
Freelancer journalist Kavin Senapathy, for example, speaks to audiences ranging from tens to thousands about science, health, food and parenting. “I bring some of my reporting into my talks, and I focus on deeply context-driven, justice-driven and evidence-driven takes on my topics,” she said.
Maryn McKenna, a newly hired senior writer at WIRED, also speaks on her specialties—public health, global health and food policy—developed as a freelance journalist and author. “I’ve written three books. And each of those books was about something different that launched me into speaking about that topic,” explained McKenna.
This was seconded by Christie Aschwanden, a science journalist, podcaster and author. Her book Good to Gocame out before the pandemic, so she spent most of 2019 promoting it. She realized she could turn her book tour into a paid speaking tour.
Prompted by a question in the Zoom chat, the panelists later cautioned the audience, especially journalists, to consider conflicts of interest when selecting speaking programs and engagements.
“I wouldn’t take money from a drug company because I write about drug development and antibiotic resistance,” said McKenna. She’s also careful about who she’s photographed with on a panel to avoid malicious actors, and she researches who is funding a potential paid event.
When developing programs, the panelists also identify their value propositions: What problems will they solve for their paying clients and their audiences?
For example, Levine teaches training webinars for professional organizations, which help her attendees advance their careers. But she also helps her paying clients, the organizations themselves. “I say to my client, it is going to help enhance your brand as career partners in this community. It’s going to bolster your membership because more people will see the value of this membership. … And it will even help bring in more sponsorship.”
Although the panelists varied in their marketing strategies, they all emphasized a need to tailor their value propositions for potential clients. For instance, like me, you may have heard of Aschwanden’s workshops on the business of freelancing. What makes them different from other freelancing workshops? “It’s not just me talking and conveying information,” she said. “The real value comes from the communities that I’m building.” In fact, she recently discovered that a group from one workshop has been getting together once a week for years.
Another thing the panelists agreed on was the main takeaway: Your time and domain knowledge is worth something when it comes to speaking, just like it is for writing. They said that it’s important to understand the minimum amount you’ll accept. And it’s important to clearly state that speaking is part of your business.
“Don’t apologize,” emphasized McKenna. “You are a professional. This is how you make your living.”
So, what should you do if a nonprofit or university says it doesn’t have a speaker budget? Unless you want to speak for free, they recommended pushing back. Levine responds by saying, “If your budget issues change, please let me know.” Or if she’s feeling less polite, “Don’t your staff members earn salaries?”
Senapathy is equally blunt. She even asks potential clients, “How much are the white men who are speaking getting paid?” and then asks for the same.
And just how much do these professional speakers charge? That was my burning question, because I’ve been teaching a lot of virtual workshops throughout the pandemic. But the SciWri attendees were asked not to disclose these dollar figures, so you’ll have to watch the recording on Whova to find out.
More information is available at the following links:
Mentor mothers using MOVIE videos during a training session (Photo by Maya Adam).
Feeding infants formula with invisible pathogens can cause life-threatening diarrhea, and introducing solid foods too early can result in nutrient deficiencies. For reasons like these, the World Health Organization and UNICEF recommend feeding infants only breast milk for the first six months, when possible.
But this guideline is rarely followed in developing countries with limited access to health care and education. In South Africa, for instance, less than a third of new mothers exclusively breastfeed for that long.
Now, Stanford Medicine researchers are trying to improve breastfeeding outcomes in South Africa by developing and testing an educational video series. These videos discuss topics such as the health benefits of breastfeeding and what to do if breastfeeding isn’t possible. After running a 19-month study, they found that video-based counseling using computer tablets can promote breastfeeding in under-resourced settings as effectively as in-person counseling.
The study was led by Maya Adam, MD, a clinical assistant professor of pediatrics and the director of Health Media Innovation at Stanford. Adam and the research team partnered with health care workers from Philani Maternal Child Health and Nutrition Trust who shared the video series — called the Philani MObile Video Intervention for Exclusive breastfeeding (MOVIE) — with new and expecting mothers in their South African communities.
“Thankfully, more and more mothers even in the hardest-to-reach communities are gaining access to mobile technology,” said Adam. This access opens up the opportunity to promote breastfeeding in these communities by designing entertaining, educational content and delivering it on mobile devices, she said.
Details of the study were published September 28 in PLOS Medicine.
Entertainment education
To create the videos, Adam collaborated with Stanford’s Digital Medic team in South Africa to harness the power of “entertainment-education.” The idea is to draw learners in with dramatic narratives, compelling visuals and soundtracks, Adam said.
The 13 videos are short: four minutes or less. A local South African artist illustrated the health and motivational messages and other local women narrated them. For example, one animated video depicts the story of a mother explaining to her daughter why she breastfed against her own mother’s advice. These illustrations were interspersed with personal narratives from three South African celebrities and four community mothers.
“Some videos were more geared towards the early newborn phase, like the common challenges video. And some were geared towards later phases, like the one aimed at supporting moms who need to return to work,” said Adam.
To test the video series’ ability to provide effective education and encourage breastfeeding, Adam’s team ran a controlled trial involving 84 community health workers, or “mentor mothers,” from the Philani Maternal Child Health and Nutrition Trust. Each mentor recruited and counseled a group of mothers in her community, with 1502 mothers participating in the study.
The mentors were randomly assigned to either the control or intervention group. One half, the traditional mentors, used only face-to-face breastfeeding counseling, while the intervention mentors spent part of their home visits showing Stanford’s videos on tablets that the study provided. The videos were viewed a total of 6,435 times during the visits.
As good as face-to-face
Throughout the study, all mentor mothers counseled their clients on infant feeding during regular home visits starting in the last trimester of pregnancy and lasting until the baby was 5 months old. The intervention mentors chose specific videos to meet the client’s needs.
Each time a baby turned 1 month old or 5 months old, the mentors surveyed the mother’s feeding practices and maternal knowledge.
The researchers observed no significant differences between breastfeeding outcomes for both mentor groups. For example, overall, about 54% of all participants reported during the 5-month survey that they were breastfeeding exclusively. The similarity of these outcomes suggests that the videos were as effective as traditional counseling when used to replace part of the home visit.
However, the videos had the benefit of allowing intervention mentors to do other health-related tasks for the families, including monitoring other children’s growth, updating and keeping medical records and completing referral forms, Adams said.
Mentor mothers also reported that carrying a tablet increased their credibility within the community, said Adam. “My hope is this research will help policymakers and funders see the great potential in equipping community health workers of all levels with mobile devices,” said Adam. “The mentors are heroes, fighting for their communities at the frontlines of health. They deserve to have the technological tools they need.”
This is a reposting of my Scope blog story, courtesy of Stanford School of Medicine.
Ritimuka “Riti” Sarangi is this year’s Lytle Award recipient. (Jacqueline Ramseyer Orrell/SLAC National Accelerator Laboratory)
Ritimukta “Riti” Sarangi, a senior scientist at the Department of Energy’s SLAC National Accelerator Laboratory, is the latest recipient of the Farrel W. Lytle Award, which recognizes important contributions to synchrotron science and efforts to support users at the Stanford Synchrotron Radiation Lightsource (SSRL), a DOE Office of Science user facility.
Since its inception in 1998, the Farrel W. Lytle Award has been given annually to SSRL staff members and users from around the world.
“Farrel is a legend in X-ray spectroscopy science. He has made contributions to every aspect of X-ray instrumentation, measurement and analysis,” Sarangi said. “I was completely unaware of my nomination and was thrilled when I received the email” notifying her of the award.
Sarangi started running experiments at SSRL in 2001, when she was a graduate research assistant at Stanford University. After earning her PhD in chemistry, she joined the SSRL staff in 2007. She is currently a senior member of the Structural Molecular Biology group at SSRL and a hard X-ray spectroscopist.
In a nomination letter for the award, Graham George, the Canada research chair in X-ray absorption spectroscopy at the University of Saskatchewan, praised Sarangi’s contributions in research, user support, outreach and leadership. “While SSRL scientific staff includes many outstanding individuals, even among this strong competition Riti stands out,” he wrote. “I have heard Riti described by senior SSRL management as an ‘anchor at SSRL,’ and I think that this description is an accurate one.”
Catalyzing discoveries
Sarangi uses X-ray spectroscopy techniques to study the fundamental properties of enzymes, molecules produced by a living organism that act as a catalyst to bring about specific biochemical reactions. Much of her research focuses on metalloenzymes, a broad group of enzymes with one or more metal ions in their active site, where other molecules bind and undergo a chemical reaction.
“Metalloenzymes perform a wide range of chemical transformations from electron transfer to small molecule activation to more complex molecular transformations,” explained Sarangi. “My goal is to apply X-ray methods towards understanding the structural and electronic details of these metal-containing active sites to shed light on the functional details of metalloenzymes and related systems.”
She is particularly interested in understanding methyl coenzyme M reductase (MCR), a unique nickel-containing enzyme responsible for the generation of 1 billion metric tons of methane annually.
Methane is the main component of natural gas and accounts for almost a quarter of U.S. energy consumption, but it is also a potent greenhouse gas. Understanding the mechanistic aspects of methane activation and synthesis is, therefore, imperative from fundamental, applied-energy, economic and environmental perspectives, Sarangi said.
Sarangi investigates metalloenzymes like MCR using modern X-ray spectroscopic tools and advanced computer simulations that model the quantum physics underlying chemical reactions.
“While spectroscopy provides an experimental window into specific properties about your system, quantum simulation methods provide additional information about structure, bonding and reactivity properties,” she said. “Experiments answer the what and theory answers the why given this specific what.”
Her nominators noted the powerful and unusual nature of her combined methodology. Stephen Ragsdale, professor of Biological Chemistry at the University of Michigan, wrote, “Riti’s approach is continuing to close the gap between experimental and computational aspects of X-ray spectroscopy. It is also absolutely crucial in understanding the complex biological systems that we and others are studying.”
In one recent study, Sarangi and colleagues combined a variety of experimental and theoretical techniques to uncover how enzymes help synthesize methane, revealing a surprising way the enzyme binds to the chemical it converts to methane. Ragsdale called the research “an extraordinary feat.”
Supporting users
Sarangi does a lot more than groundbreaking research, spending much of her time supporting the SSRL user community. “Riti is engaged at every level with user support and is someone who is not afraid to get her hands dirty,” George wrote.
For example, she developed a computer cluster for implementing various theoretical packages that simulate, interpret or augment experimental X-ray spectroscopy data.
“When I started at SSRL in a user support role, I realized these theoretical tools were rarely leveraged by our biological user community and therefore the full potential of their X-ray datasets was often not realized,” said Sarangi. “While I have continued to apply theoretical tools to my own research program, I have also established and made available a high-speed computational cluster to the entire bio-spectroscopy and bio-inspired catalysis user community.”
She has also been crucial to keeping SSRL running during the COVID-19 pandemic, her nominators said.
“She played a pivotal role in generating online access programs and coordinating communication and timeline details so users could continue to accomplish our science during the time when SSRL was closed for visitors,” Timothy Stemmler, assistance vice president for research and professor of pharmaceutical sciences at Wayne State University, wrote in a letter. “Her efforts to allow online access will surely transform how data is collected at the entire lab moving forward, and will lead to many future discoveries, he wrote.
The nominators also applauded Sarangi’s mentoring, training and recruitment of the next generation of scientists. “She has clear skills in organizing and delivering training content and this sets her apart as not just an amazing colleague, but an amazing educator,” wrote Stemmler.
Envisioning the future
Looking forward, Sarangi thinks the lessons learned during the pandemic suggest that more researchers could work remotely – something she said accelerated her scientific and operational engagement with staff, users and collaborators. In 20 years, she expects SSRL X-ray science to become an automated and high-throughput experience that integrates multiple complementary X-ray and non-X-ray measurements.
She is also leading efforts to plan the future of structural science at lightsources, based on a series of workshops whose reports will develop a robust case for investing in X-ray science.
“This is no easy task and has required mastering the details of techniques adjacent to her expertise, diplomacy in bringing diverse ideas in different disciplines together, and hard work,” wrote Edward Snell, chief executive officer of the Hauptman-Woodward Medical Research Institute, in a nominating letter.
George also praised Sarangi’s leadership and vision. “I have had the distinctive privilege of knowing Farrel quite well, and I am certain that he would approve of this nomination,” he wrote. “The SSRL Users’ executive committee would be hard pressed to find a better candidate.”
Aisulu Aitbekova, a 2021 doctoral graduate from Stanford University, discovered her passion for research when she traveled from Kazakhstan to the U.S. for a summer internship as a chemical engineering undergraduate. She said that experience inspired her to go to graduate school.
After earning a master’s in chemical engineering at the Massachusetts Institute of Technology, she continued her studies at Stanford University under the supervision of Matteo Cargnello, an assistant professor of chemical engineering and Aitbekova’s doctoral advisor. Much of her thesis work involved beamline studies at the Stanford Synchrotron Radiation Lightsource (SSRL) at the Department of Energy’s SLAC National Accelerator Laboratory.
Now, Aitbekova has been selected to receive the 2021 Melvin P. Klein Scientific Development Award, which recognizes outstanding research accomplishments by undergraduates, graduate students and postdoctoral fellows within three years of completing their doctoral degrees.
In a nomination letter for the award, SLAC Distinguished Staff Scientist Simon Bare praised Aitbekova’s initiative. “She has quickly become proficient in the application of X-ray techniques available at the synchrotron at SLAC. This proficiency and mastery include everything from operating the beamline to analyzing and interpreting the data,” he wrote.
Aitbekova said she felt “absolutely thrilled and grateful” to all of her mentors when she found out about winning the award.
“I’m so thankful for my PhD advisor Matteo Cargnello. My success would not have been possible without his mentorship,” Aitbekova said. “I’m also particularly grateful to Simon Bare, who I consider to be my second advisor. His continuous excitement about X-ray absorption spectroscopy has been the driving force for my work at SSRL.”
Catalyzing change
Aitbekova said she is passionate about finding solutions to combat climate change. She designs materials to convert harmful pollutant gases into useful fuels and chemicals. To perform these chemical transformations, she develops catalysts and studies their properties using X-ray absorption spectroscopy (XAS). Catalysts are substances that increase rates of chemical reactions without being consumed themselves.
“I have identified that a catalyst’s size, shape and composition profoundly affect its performance in eliminating these gases,” but exactly how those properties affect performance remains unknown, she said. “This problem is further complicated by the dynamic nature of catalytic materials. As a catalyst performs chemical transformations, its structure changes, making it challenging to precisely map a catalyst’s properties to its performance.”
To overcome these barriers, she engineers materials the size of one ten-thousandth the diameter of a human hair and then tracks how they change during reactions using XAS.
In one study, Aitbekova and her colleagues engineered a catalyst using a combination of ruthenium and iron oxide nanoparticles, which they think act in a tag-team fashion to improve the synthesis of fuels from carbon dioxide and hydrogen. Using a prototype in the lab, they achieved much higher yields of ethane, propane and butane than previous catalysts.
Switching gears
While engineering catalysts that convert carbon dioxide into chemicals, she developed a new approach for preparing materials, where small particles are encapsulated inside porous oxide materials – for example, encapsulating ruthenium within a sheath of iron.
However, Aitbekova recognized a completely different application for this new approach: creating a palladium-platinum catalyst that works inside a car’s emission control system.
To eliminate the discharge of noxious emission gases, cars are equipped with a catalytic converter. Exhaust gases pass into the catalytic converter, where they are turned into less harmful gases. The catalysts inside these units are platinum and palladium metals, but these metals gradually lose their efficiency due to their extreme working conditions, she said.
“My platinum and palladium catalysts show excellent stability and performance after being subjected to air and steam at 1,100 degrees Celsius, the harshest operating environment automotive exhaust emission control catalysts could be subjected to,” explained Aitbekova. “Further improvements in these materials and successful testing under true exhaust conditions have a potential to revolutionize the field of automotive exhaust emission control.”
Her nominators agreed, citing it as the highlight of her graduate career.
“This work, currently under review for publication, is truly the remarkable result of Aisulu’s hard work and experience in pivoting from one area to another to make an impact and of her ability to connect multiple fields and solve important problems,” Cargnello wrote.
Amplifying impact
Despite this success, Aitbekova is already focused on how to make an even greater impact through mentoring and future research.
Her nominators all applauded her passion and commitment to mentor the next generation of STEM scholars, as demonstrated by mentoring “a countless number of undergraduates” according to Cargnello and by exchanging letters with middle school students from underrepresented groups.
Part of this passion, Cargnello and others wrote, stems from her experiences growing up in a highly conservative environment with the understanding that homemaking would be her eventual job. Aitbekova’s nominators wrote that they admired the fact that she made her way to Stanford and has acted as an ambassador for the values and principles of diversity and inclusion.
Aitbekova said she embraces the role. “Since my first summer research experience in the USA, I’ve wanted to serve as a bridge to science and graduate school to those who, like me, didn’t have access to such knowledge and resources.”
She will continue to act as a bridge in her next endeavor as a Kavli Nanoscience Institute Prize Postdoctoral Fellow at Caltech, where she plans to expand her work of converting carbon dioxide into fuels by running the chemical transformations with solar energy. That will “bring society one step closer to sustainable energy sources,” she said.
Bare and others praised her drive to make an everyday impact. “She has a natural passion for wanting to understand the physical principles behind the phenomena that she has observed in her research. But this passion for understanding is nicely balanced by her desire to discover something new, and to make a real difference — the practicality that is often missing in someone early in their career,” wrote Bare.
Anyone with an aching back knows just how debilitating that pain can be. Now, Stanford Medicine researchers may have good news for the 500 million people worldwide experiencing low back pain.
Stanford pain psychologist Beth Darnall, PhD, has developed a single-session, two-hour class called Empowered Relief, which aims to rapidly equip patients with pain management skills. The first randomized, controlled clinical trial suggests this new method may be as effective at reducing chronic low back pain as weeks of traditional therapies, a paper in JAMA Network Open recently reported.
Empowered Relief stems from a traditional therapy called cognitive behavioral therapy, which relies on the interconnection between thoughts, feelings, physical sensations and actions. Both treatments can help patients identify and change thoughts and behaviors that increase their pain, as well as learn coping skills to better control pain response and improve quality of life.
“The problem is CBT isn’t broadly accessible,” said Darnall. “There are only a small number of behavioral specialists, and yet millions of Americans live with ongoing pain. And many under-served communities in the U.S. don’t know how to find a trained therapist.”
Another major barrier, said Darnall, is time commitment — cognitive behavioral therapy patients attend a two-hour group session each week for two to three months.
To address this problem, Darnall combined what she believed were the most critical skills from cognitive behavioral therapy, such as identifying unhelpful and stressful thought patterns, with information about the science of pain, mindfulness principles, and the relaxation response. With the help of an instructor, patients then translate their new skills and knowledge into a personalized plan to manage their pain at home.
“The goal is to align our treatments with what’s feasible for patients and make it broadly accessible,” Darnall said. It’s possible, she said, to teach 85 people in a one-and-done Empowered Relief class. And if taught weekly, 680 patients could be treated in eight weeks, compared with 10-15 who could be treated during that time with cognitive behavioral therapy.
Pain treatment with lasting effects
Darnall conducted the clinical study with Sean Mackey, MD, PhD, professor of anesthesiology, perioperative and pain medicine at Stanford. In it, 263 adults with chronic low back pain — most of whom had this pain for more than five years and almost half of whom had additional chronic pain conditions — were randomly assigned to eight cognitive behavioral therapy sessions, one Empowered Relief session or one traditional health education session, which acted as a control. (In health education, participants learned basic information, such as the definition and warning signs of back pain, but not actionable skills or the neurobiology of pain.)
For three months after the treatment, the participants reported information about their pain, such as its intensity and whether it disturbed their sleep. According to patient reporting, Darnall’s course relieved pain as effectively as cognitive behavioral therapy and better than the health education session.
“I was pleasantly surprised that people’s back pain improved as well as their sleep, depression and anxiety symptoms,” said Mackey. “I can easily see this integrating with standard medical care to provide benefits for many patients.”
The results are promising, but the study will need to be replicated in a larger and more diverse population, said Darnall.
The success of the course doesn’t mean cognitive behavioral therapy will be eliminated, Darnall said. Instead, the researchers want to determine how to match individual patients with treatment options that work best for them. That, she said, could inform pain treatment protocols, resource allocations and other medical decision-making.
Now, Darnall’s team is expanding access to the Empowered Relief program to help address existing disparities in pain care. The class is already available in five languages and seven countries to treat chronic pain — and the team has certified 300 healthcare clinicians around the world as Empowered Relief instructors.
“I hope expanded, online access to the course will provide more equitable access to evidence-based pain care for people living in rural areas, prisons and other settings that lack trained pain professionals,” she said.
With less than half of the United States fully vaccinated, you’ve probably wondered, “How should I talk to hesitant friends or family members about getting their COVID-19 shot?” Now, Stanford Medicine researchers specializing in health education have developed guidelines to help facilitate those awkward conversations.
“We’re trying to find common ground between different audiences to create guidelines that catalyze conversation about vaccination, not stifle it,” said Rachelle Mirkin, MPH, administrative director of health education, engagement and promotion at Stanford Health Care, who led the effort.
Moreover, these conversations either aren’t happening or they’re often ineffectively divisive, said Emilie Wagner, a healthcare strategy consultant who teaches at Stanford and who helped Mirkin and Nicole Altamirano, program manager for digital experience strategy, conduct the research. “There’s so much tension that people don’t want to risk a relationship. Yet, if it goes unaddressed, the tension just naturally mounts.”
The team wanted to understand why some people are reluctant to adopt COVID-19 prevention measures — including wearing a mask, social distancing and being vaccinated — and wanted to learn how to facilitate better communication with vaccine-hesitant individuals.
So far, they’ve discovered that traditional messages — such as the need to protect yourself and others or the enticement of getting kids back to school — don’t move the needle when it comes to persuading hesitant people to get a vaccine. Having a personal, empathetic conversation with people works better than presenting statistics and facts at them.
Needing a new approach
Mirkin and her team conducted an extensive literature review of vaccine hesitancy, using the information to create a list of 25 talking points they thought might sway those who are vaccine hesitant.
They then interviewed health care providers, hospital administrators and a small group of older white adults who were vaccine hesitant, but only regarding COVID-19. Somewhat surprisingly, these participants weren’t generally against vaccines, said Mirkin. Some had already received a two-part shingles vaccines, which can have significant side effects including fatigue, muscle pain and fever.
But when it came to COVID-19 shots, the traditional messaging did not resonate with the target group, said Wagner.
“They had a response for everything,” she said. “They thought the vaccine wasn’t a means for returning to normal. It wasn’t their responsibility to keep others safe. And they believed the risk of the vaccine outweighed the risk of COVID.”
So, the team switched from drawing on knowledge to drawing on empathy. Instead of focusing primarily on facts, they suggest having open-ended conversations that validate feelings and personalize the vaccine experience. And they recommend talking about how everyday life is easier once you’re vaccinated.
According to Wagner, they found that the appeal of hassle-free travel can motivate this group to get vaccinated. Visiting with grandkids can also nudge older adults into getting their shots. But generally, it takes a combination of incentives. The researchers also realized that many short conversations over time are needed. “It takes persistence, so talking with friends and family members can be more effective than a single conversation with a provider,” Wagner said.
To share their approach more broadly, the researchers translated their new strategy into two practical guides — one for health care providers and one for friends and family — and are now disseminating them.
“We need to make space for these discussions,” Mirkin explained. “The more non-judgmental conversations you have with an individual, the more likely they are to protect themselves and others from COVID.”
Encouraging vaccine acceptance, one group at a time
Mirkin’s team is also trying to understand the drivers of vaccine acceptance in two other groups: Latino Spanish speakers and Pacific Islanders. They are working with community partners to create social media campaigns, including Facebook ads, Twitter and Instagram posts, as well as public service announcements. So far, the Latino public service announcements have been picked up by Telemundo, a Spanish-language television network, and the Facebook ads have more than 3 million hits.
Based on initial data, the main issue for Latinos and Pacific Islanders is access to personal protective equipment — such as masks — COVID-19 testing and vaccines, Mirkin said. “In general, the concerns are very logistics-based, whereas the Caucasian hesitant group is philosophically- and identity-based,” she said.
Vaccine acceptance is often complicated by a larger erosion of trust of science and health care systems that have failed many people, especially those of color, said Mirkin. “As an academic medical center, we have to understand what’s going on to begin to reshape the conditions to help rebuild trust.”
This is a reposting of my Scope blog story courtesy of Stanford School of Medicine.
Calvin Kuo, MD, PhD, with Shannon Choi, MD, PhD, a student in the Kuo lab. Courtesy Steve Fisch
A year into the pandemic, we’ve all heard the stories. A patient is a little short of breath but appears to have a mild case of COVID-19. The next day, she deteriorates so rapidly that she’s rushed to intensive care, put on a ventilator, and hooked up to a dialysis machine to prevent kidney failure. Her overzealous immune system has gone rogue, attacking healthy cells instead of just fighting off the virus.
What triggers this devastating immune response, called a cytokine storm? Researchers are still struggling to identify the underlying processes that initiate a COVID infection and subsequent cytokine storm.
Biologists use advanced technologies and cell cultures in petri dishes to study severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the coronavirus strain responsible for COVID-19, identifying its key characteristics such as the famous crownlike spikes on their surfaces. But these short-lived cultures don’t act like real organs. And scientists are limited by their samples.
“When you analyze samples from patients, they’re often at the end stage of the disease, and many of the samples are from autopsy. You can’t understand the initiation process because the tissue is essentially destroyed,” says Calvin Kuo, MD, PhD, professor of hematology.
Understanding how the disease develops and testing potential treatments require better ways to model this coronavirus.
Miniature Organs in a Dish
Kuo’s laboratory develops organoids—three-dimensional miniature organs grown in a petri dish that mimic the shape, structure, and tissue organization of real organs.
Grown from human tissue samples using precisely defined ingredients, these organoids are little spheres of gel up to 1 millimeter in diameter. Healthy tissue samples are mechanically minced and enzyme digested to get to single cells, and then the organoids are grown from single stem cells. They last about six months, significantly longer than the few-weeks lifetime of traditional cell cultures.
Kuo initially developed organoids to study stem cell biology and model cancer. His team was the first to use organoids to convert normal tissues to cancer, as previously reported in Nature Medicine.
But he was passionate about using organoids to model infectious diseases. In 2015, he led a National Institute of Allergy and Infectious Diseases U19 research program, recently renewed for an additional five years, in collaboration with Stanford researchers Manuel Amieva, MD, professor of pediatrics and of microbiology and immunology; Harry Greenberg, MD, the Joseph D. Grant Professor in the Stanford University School of Medicine and professor of microbiology and immunology; Elizabeth Mellins, MD, professor of pediatrics; and Sarah Heilshorn, PhD, professor of materials science and engineering. Focusing mainly on the gastrointestinal tract, this multidisciplinary team provided proof of principle that organoids could model infectious diseases.
“With an organoid system, you can start at the infection and look at the very earliest events that occur after infection. And those can give insights as to what needs to be blocked therapeutically,” Kuo explains.
Distal Lung Organoids
After the initial success with gastrointestinal organoids, Ameen Salahudeen, MD, PhD, a hematology and oncology postdoctoral fellow working in Kuo’s lab, led efforts to expand this work by developing distal lung organoids. He partnered with lung stem cell expert Tushar Desai, MD, associate professor of pulmonary, allergy, and critical care medicine at Stanford.
The distal lung is composed of terminal bronchioles and alveolar air sacs, where inhaled air passes through the tiny ducts from the bronchioles into the elastic air sacs. It performs essential respiratory functions that can be compromised by inflammatory or infectious disorders, such as COVID-19 pneumonia.
“Growing distal lung cultures in a pure way that doesn’t require any supporting feeder cells and is in a chemically defined media had not been possible,” Kuo says. “We were able to do this very beautifully—to grow alveoli at the terminal bronchioles as long-term human cultures.”
The team developed two types of distal lung organoids. Both were made from human distal lung samples provided by Stanford cardiothoracic surgeon Joseph Schrager, MD.
They grew the first type, alveolar organoids, from single alveolar type 2 (AT2) stem cells. AT2 cells have several important functions that together help control the immune response to decrease lung injury and repair. The scientists then induced the AT2 cells to produce alveolar type 1 (AT1) cells, which are the thin-walled cells lining the alveolar air sacs; they are essential for the lung’s gas-exchange function.
“The second type are the basal organoids, which grow from single basal stem cells. They give rise to the mucus-secreting club cells and the ciliated cells with beating hair. And we can see the beating hair under the microscope—it’s quite dramatic,” describes Kuo. “That’s a very nice reproduction of the differentiation and function of the lung.” The team also grows a mixture of alveolar and basal organoids.
They selected these organoid types to determine which cell types in the bronchioles and alveoli were infectible—in hopes of identifying the different mechanisms for how viruses cause respiratory compromise.
Initially, they tested the distal lung organoids using the H1N1 influenza virus, collaborating with Stanford molecular virology expert Jeff Glenn, MD, PhD.
The team fluorescently labeled the virus and infected the lung organoids, demonstrating that the virus replicated in both basal and alveolar organoids. Next, they did more sophisticated PCR-based testing to show that the virus replicated its genome.
COVID-19 Model
“But then the COVID-19 pandemic hit, so we initiated a fabulous collaboration with infectious disease expert Catherine Blish, MD, PhD, in the Department of Medicine, to infect our lung organoids with SARS-CoV-2. This was driven by a talented MD-PhD student in my lab, Shannon Choi,” says Kuo. “She worked with Arjun Rustagi, an infectious disease fellow in Catherine Blish’s lab, who infected the organoids in a biosafety-level-3 lab.”
Another partnership was critical, though. An important coronavirus receptor, called angiotensin-converting enzyme 2, or ACE2, resides inside the lung organoids. But ACE2 needed to be on the outside of the organoid to get the infection going.
Luckily, Amieva previously devised a way to flip intestinal organoids inside out. Working together, Choi and Amieva turned the lung organoids inside out.
As reported in Nature in November 2020, the team demonstrated that the coronavirus infected their distal lung organoids, including the alveolar air sacs, where COVID-19 pneumonia originates. They also identified a new airway subpopulation as a COVID-19 virus target cell.
“Everyone knew basal cells were stem cells in the lung, but they thought they were all equivalent. Using our organoids, we discovered an unknown basal cell subpopulation containing the stem cell activity. And then we showed this subpopulation actually existed in human lungs in very interesting anatomic locations,” Kuo says.
COVID-19 Applications
According to Kuo, their distal lung organoids have three major applications for COVID-19.
They are using them to screen potential coronavirus therapeutic antibodies and to understand how these treatments work. Although initially focused on COVID-19, this screening will likely expand to other kinds of lung infections in the future.
Because the distal lung with the alveoli is the site of the COVID-19 pneumonia, they also plan to use the organoids to identify the underlying biological mechanisms behind coronavirus infection. Finally, they plan to extend their organoid system to incorporate immune cells and understand more complex processes. In particular, they plan to model the dreaded cytokine storm.
Overall, Kuo emphasizes that this organoid research represents a huge team effort involving many investigators with wide-ranging expertise from various departments at Stanford, as well as an “interesting evolution of events.” “Now we have a human experimental system to model SARS-CoV-2 infection of the distal lung with alveoli, which is the site of the lung disease that kills patients,” he summarizes. “We know patients die because of severe pneumonia and lung failure. We can now recapitulate this in the dish. So, we can study how it works, and also test drug treatments.”
This is a reposting of my feature article in the recent Stanford Medicine Annual Report. Check it out to see videos of these lung organoids.
Many blood and immune disorders could be cured by transplanting healthy blood stem cells from a matched donor. But first the patients need a pretreatment procedure to eliminate their own blood stem cells, making room in the bone marrow for the donor cells to take their place.
The problem is that the standard pretreatments—chemotherapy or radiation—are very toxic. Doctors don’t want to give them to vulnerable children, such as those with a rare genetic disorder called severe combined immunodeficiency (SCID).
Infants with SCID have compromised immune systems that struggle to fight off even common infections caused by viruses and fungi. These babies have many chronic and life-threatening problems, including frequent lung infections, chronic diarrhea, and recurrent sinus infections.
Judy Shizuru, MD, PhD, reviews data with Wendy Pang, PhD
“Without treatment, SCID infants usually die from infections within the first two years of life. Blood stem cell transplants are the only definitive cure for this disease,” says Judith Shizuru, MD, PhD, professor of blood and marrow transplantation and cellular therapy and of pediatrics. “But transplants usually involve chemotherapy, and we don’t want to give these agents to these children because they’re particularly susceptible to the damaging short-term and long-term effects—including growth defects, neurological problems, and increased risk of cancers. This is especially true for certain subtypes of SCID.”
Instead, SCID patients are often given a blood stem cell transplant without pretreating with chemotherapy to create space in their bone marrow. But then the donors’ self-renewing blood stem cells may not fully engraft, so the kids can’t robustly regenerate their immune systems. These children have to rely on regular intravenous immunoglobulin infusions to boost their immune response, and the effectiveness of donor immune cells can wane over time.
The great need for a less toxic pretreatment for blood stem cell transplants inspired Shizuru to initiate a Stanford study testing a novel antibody pretreatment in SCID patients—in collaboration with Rajni Agarwal-Hashmi, MD, associate professor of pediatrics, and other stem cell transplantation and regenerative medicine specialists at Stanford and UC-San Francisco.
Targeting Blood Stem Cells
The novel pretreatment uses the JSP191 antibody to target a protein called CD117, found on the surface of blood stem cells. The antibody binds to this protein, which then blocks CD117 from binding to a stem cell factor critical for keeping blood stem cells alive. When the interaction between CD117 and the essential stem cell factor is interrupted, the patient’s blood stem cells are depleted—making space for the donor’s healthy cells to engraft.
“It’s not like chemotherapy or radiation,” says Shizuru. “It’s a targeted way to deplete the blood stem cells without damaging normal healthy cells.”
The Stanford team chose SCID patients for their first human JSP191 clinical trial in part because these children have a unique biology—they lack lymphocytes, so they are less likely to immunologically reject the blood stem cells from a donor. Since immune suppressive medications aren’t necessary, the researchers can more easily see if the antibody therapy clears space in the bone marrow and the transplant works.
Initially, the clinical trial studied older children and adults with SCID whose first blood stem cell transplant had failed, so that they could evaluate whether JSP191 therapy was safe and well tolerated. The participants ranged in age from 3 years old to mid-30s, but most were between 11 and 13 years old. According to Shizuru, many of these kids had chronic infections and also wanted to be liberated from having intravenous immunoglobulin infusions.
Rajni Agarwal-Hashmi, MD
Promising Results
The results are very promising, as Shizuru reported in 2019 at the American Society of Hematology annual conference. The antibody safely created room in the patients’ bone marrow, allowing healthy donor stem cell engraftment without common side effects like transfusion reactions, treatment-related toxicities, or bone marrow suppression.
“The wonderful thing about the antibody JSP191 is it’s super-safe. This conditioning agent doesn’t affect the DNA or any other organ, as far as we can tell,” explains Shizuru. “We give it as a onetime, really low dose. And it’s not showing any side effects. It’s an amazing drug.”
The study’s clinicians even remarked that the re-transplant kids looked bored in the hospital because the expected complications didn’t happen, says Shizuru. “The patients’ counts didn’t drop. They didn’t have increased infections. They didn’t need blood transfusions,” she says. “So, we decided to give the antibody as an inpatient treatment and then do everything else as outpatient after 48 hours.”
The results were promising from the start. The first participant pretreated with JSP191 was a 3-year-old girl with chronic diarrhea and infections. After about a year, she no longer had diarrhea and started going to school for the first time. In fact, her family was infected with COVID-19 and she did fine, as Shizuru learned during a public discussion.
Expanding the Clinical Trial
Based on the safety and success of the first phase, the JSP191 trial expanded to include infants newly diagnosed with SCID. Two infants have received the antibody pretreatment followed by a blood stem cell transplant.
The first infant did really well, demonstrating signs that his donor cells may fully restore his immune function. The second infant’s response was more complicated; the researchers determined that she had some immune function that may have rejected the maternal stem cells. She subsequently underwent another transplant without the antibody agent, using a mix of chemotherapies.
After their initial success, Shizuru’s team expanded the use of JSP191 to include other vulnerable populations—older adults with acute myeloid leukemia (AML) or myelodysplastic syndromes (MDS). AML is a type of leukemia in which DNA mutations cause the rapid growth of abnormal cells that build up in the bone marrow. Although it starts in the bone marrow, AML often quickly moves to the blood and sometimes spreads to other parts of the body. MDS are a group of diverse bone marrow disorders in which the bone marrow does not produce enough healthy blood cells. Both AML and MDS primarily occur in people over 65 years old.
This adult study is based on the preclinical work of Wendy Pang, MD, PhD, who was a postdoctoral fellow in the Shizuru laboratory. She showed that the disease-causing MDS and AML stem cells express CD117, so they can be targeted by JSP191. Further, the team observed synergistic eradication of stem cells when these anti-CD117 antibodies were combined with low-dose radiation.
The ongoing clinical trial utilizing JSP191 combined with low-dose radiation is led by Lori Muffly, MD, assistant professor of blood and marrow transplantation and cellular therapies. The preliminary results are encouraging based on the first six participants, who were older adults (64–74 years old) with AML or MDS. The researchers observed no side effects associated with JSP191, and the patients’ blood stem cell transplants were successful.
“We transplanted our first SCID babies and then opened the trial up to older patients with AML and MDS. So, now we’re covering the full spectrum for this targeted therapy: from a 3-month-old infant with SCID to a 74-year-old with AML,” Shizuru says.
The JSP191 project has now moved to a biotechnology company, Jasper Therapeutics. Shizuru expects that in the future, the studies will expand to include sickle cell disease, a group of inherited red blood cell disorders, where the JSP191 antibody can help to engraft the donor cells.
“In terms of pretreatment, there’s been no innovation on transplant agents in decades. People have been innovating on transplant by simply reducing the dose of chemotherapies, but we haven’t seen a successful new agent,” explains Shizuru. “The development of JSP191 leverages our understanding of the biology of blood stem cells by targeting a critically important molecule. JSP191 antibody is now the platform agent.”
This is a reposting of my feature article in the recent Stanford Medicine Annual Report.
Scientists Talk Funny 