“Looking in the patients’ eyes and having a conversation” has motivated Stanford oncologist Ash Alizadeh, MD, PhD, to improve the way we diagnose, talk about and treat cancer.
Patients go home nervous and the care team is nervous, he pointed out, because you’re fighting a battle together to save a life and the things you’re doing are toxic and expensive.
“It’s really sobering to look at how blunt our tools are for getting a sense for whether you’re making progress as you’re going through the course of your therapy,” said Alizadeh in a recent episode of the Sirius radio show The Future of Everything hosted by Russ Altman, MD, PhD.
A key area of his work aims to more accurately predict a patient’s prognosis. He developed a computer algorithm (the focus of a recent Stanford Medicine magazine article) that searches data for information likely to affect the patient’s long-term outcome — generating a unique personalized estimate of risk, called the continuous individualized risk index (CIRI). The goal is to use CIRI to guide personalized therapy selection.
In the episode, he explained that their integrated approach better forecasts a patient’s prognosis by analyzing the complete medical path of the patient, whereas oncologists typically give more weight to the most recent data.
In the study, they also measured the amount of circulating tumor DNA (ctDNA) in the blood of 132 DLBCL patients, before and during their treatment. Circulating tumor DNA is DNA that was shed from dying tumor cells and released into the bloodstream.
For this small group of DLBCL patients, standard methods to forecast how well a patient will do had a predictive index of 0.6, where a perfectly accurate test would score 1 and a random test like a coin toss would score 0.5. Alizadeh’s CIRI score was 0.8 for the same patients — not perfect but markedly better than the current “crystal ball exercise,” he said in a news release.
In the radio show, he also discussed how this predictive model complements his work to develop new technologies for cancer diagnosis and treatment.
For example, he explained measuring ctDNA levels with a non-invasive liquid biopsy may help detect early-stage cancer, guide treatment selection and monitor treatment response. And if liquid biopsies detect cancers at an early stage, this may allow oncologists to leverage their patients’ immune system to attack their cancer, he said.
“So instead of directly attacking the tumor cells with drugs that kill the cancer cells, you now have drugs that engage the immune system to say, ‘Hey, wake up,’” he said. That means the same drug could work for many cancers.
Alizadeh is developing these new techniques to personalize cancer diagnosis and treatment in hopes of improving the outcomes for his patients, he said.
In a new series, “Behind the Scenes,” we’re inviting Stanford Medicine physicians, nurses, researchers and staff to share a glimpse of their day.
As a science writer, I talk to a lot of health care providers about their work. But I’ve often wondered what it is really like to be a surgeon. So I was excited to speak with pediatric surgeon Stephanie Chao, MD, about her day.
Chao is a pediatric general surgeon, an assistant professor of surgery and the trauma medical director for Stanford Children’s Health. In addition to performing surgeries on children of all ages, she has a range of research interests, including how to reduce gun-related deaths in children and the hospital cost associated with pediatric firearm injuries.
Morning routine On days that I operate, I get up between 5:50 and 6 a.m., depending on whether I hit the snooze button. I typically don’t eat breakfast. I don’t drink coffee because I don’t want to get a tremor. I’m out the door by 6:30 a.m. and at the hospital by 7 a.m. I usually go by the bedside of the first patient I’m going to operate on to say hi. The patient is in the operating room by 7:30 a.m. and my cases start.
On non-surgical days, it’s more chaotic. I have a 3-year-old and 1-year-old. So every day there’s a jigsaw puzzle as to whether my husband or I stay to get the kids ready for preschool, and who comes home early.
Part of Stephanie Chao’s day involves checking on patients, including this newborn.
In the operating room The operating room is the place where I have the privilege of helping children feel better. It’s a very calming place, like a temple. When I walk through the operating room doors, the rest of the world becomes quiet. Even if it is a high-intensity case when the patient is very sick, I know there is a team of nurses, scrub techs and anesthesiologists used to working together in a well-orchestrated fashion. So even when the unexpected arises, we can focus on the patient with full confidence that we’ll find a solution.
There are occasions when babies are so sick that we need silence in the operating room. Everyone becomes hyper-attuned to all the beeps on the monitors. When patients are not as critically sick, I often play a Pandora station that I created called “Happy.” I started it with Pharrell Williams’ “Happy” and then Pandora pulled in other upbeat songs, including a bunch of Taylor Swift songs, so everyone thinks I’m a big Taylor Swift fan.
The OR staff call me by my first name. I believe that if everyone is relaxed and feels like they have an equal say in the procedure, we work better as a well-oiled machine for the benefit of the patient.
“The OR staff call me by my first name,” Stephanie Chao said.
Favorite task Some of the most rewarding times of my day are when I sit down with patients and their families to hear their concerns, to reassure them and to help them understand what to expect — and hopefully to make a scary situation a little less so. As a parent, I realize just how hard it is to entrust one’s child completely in the hands of another. I also like to see patients in the hospital as they’re recovering.
Favorite time The best part of the day is when I come home. When I open the door into the house, my kids recognize that sound and I hear their little footsteps as they run towards the door, shrieking with joy.
Evening ritual When my husband and I get home, on nights I am not on call, I cook dinner in the middle of the chaos of hearing about the kids’ day. Hopefully, we “sit down” to eat by 6:20 or 6:30 p.m., and I mean that term loosely. It’s a circus, but eventually everyone is somewhat fed.
And then we do bath time and bedtime. There’s a daily negotiation with my three-year-old on how many books we read before bed. On school nights, she’s allowed three books but she tries to negotiate for 10.
Eventually, we get both kids down for the night. Then my husband and I clean up the mess of the day and try to have a coherent conversation with each other. But by then both of us are exhausted. I try to log on again to finish some work, read or review papers. I usually go to sleep around 11 p.m.
Managing it all When I can carve out time to do relaxing things for myself, like go to the gym, that is great. But it’s rare and I remind myself that I am blessed with a job that I love and a wonderfully active family.
The result sometimes feels like chaos, but I don’t want to wish my life away waiting for my kids to get older and for life to get easier. Trying to live in the moment, and embracing it, is how I find balance.
Photos by Rachel Baker
This is a reposting of my Scope blog story, courtesy of Stanford School of Medicine.
I remember when you could ride BART for free on a “Spare the Air” day, when smog was expected to reach unhealthy levels based on standards set by the Environmental Protection Agency. Now, there are too many of these days — 26 in the Bay Area last year — to enjoy that perk.
This bad air is making us sick, according to Stanford allergy specialist and clinical associate professor Sharon Chinthrajah, MD. In a recent episode of the Sirius radio show “The Future of Everything,” she spoke with Stanford professor and radio host Russ Altman, MD, PhD, about how we can combat the negative health impacts of air pollution.
“Poor air quality affects everybody: healthy people and people with chronic heart and lung conditions,” said Chinthrajah. “And you know, in my lung clinic I see people coming in with exacerbations of their underlying lung diseases like asthma or COPD.”
On Spare the Air days, Chinthrajah said even healthy people can suffer from eye, nose, throat and skin irritations caused by air pollution. And the health impacts can be far more serious for her patients. So she tells them to prepare for bad air quality days and to monitor the air quality index (AQI) in their area, she said.
The AQI measures the levels of ozone and other tiny pollutants in the air. The air is considered unhealthy when the AQI is above 100 for sensitive groups — like people with chronic illnesses, older adults and children. It’s unhealthy for everyone when the AQI is above 150.
On these unhealthy air days, Chinthrajah recommends taking precautions:
Limit the time you spend outdoors.
When outside, use a well-fitted air mask that filters out pollutants larger than 2.5 microns (which is about 20 times smaller than the thickness of an average human hair).
When driving, recirculate the air in your car and keep your windows closed.
Stay hydrated.
Once inside, change your clothes and take a quick shower before you go to bed, removing any air particulates that collected on you during the day.
In the radio show, Chinthrajah explained that published studies by the World Health organization and others demonstrate that people who live in developing countries like India and Asia — where they suffer poor air quality many days of the year — have a shortened life span.
“You know, there’s premature deaths. There’s exacerbation of underlying lung issues and cardiovascular issues. There’s more deaths from heart attacks and strokes in countries where there is poor air quality,” she said.
She admitted that it is difficult to definitively say these health problems are due to poor air quality — given the other problems in the developing country
es like limited access to clean water, food and health care — but she thinks poor air quality is a major contributor.
Chinthrajah said she believes we need to address the problem of air pollution at a societal level. And that means we need to target cars that burn fossil fuel, which account for much of the air pollution in California, she said. Instead, we need to move towards using public transportation and electric vehicles, as well as generating electricity from clean energy sources like solar, wind and water.
She noted that California is now offering a $9,5000 subsidy to qualifying low-income families to purchase low emission vehicles like all-electric cars or plug-in hybrids, on top of the standard federal and state rebates.
“So it seems like an overwhelming, daunting task, right? But I think we each have to take ownership of what we can do to reduce our carbon footprint. And then lobby within our local organizations to create practices that are sustainable,” she said.
Chinthrajah hopes that addressing air pollution and energy consumption at a societal level will lead to less asthma and other health problems, she said.
SLAC scientists and collaborators are developing 3D copper printing techniques to build accelerator components.
Imagine being able to manufacture complex devices whenever you want and wherever you are. It would create unforeseen possibilities even in the most remote locations, such as building spare parts or new components on board a spacecraft. 3D printing, or additive manufacturing, could be a way of doing just that. All you would need is the device materials, a printer and a computer that controls the process.
Diana Gamzina, a staff scientist at the Department of Energy’s SLAC National Accelerator Laboratory; Timothy Horn, an assistant professor of mechanical and aerospace engineering at North Carolina State University; and researchers at RadiaBeam Technologies dream of developing the technique to print particle accelerators and vacuum electronic devices for applications in medical imaging and treatment, the electrical grid, satellite communications, defense systems and more.
In fact, the researchers are closer to making this a reality than you might think.
“We’re trying to print a particle accelerator, which is really ambitious,” Gamzina said. “We’ve been developing the process over the past few years, and we can already print particle accelerator components today. The whole point of 3D printing is to make stuff no matter where you are without a lot of infrastructure. So you can print your particle accelerator on a naval ship, in a small university lab or somewhere very remote.”
3D printing can be done with liquids and powders of numerous materials, but there aren’t any well-established processes for 3D printing ultra-high-purity copper and its alloys – the materials Gamzina, Horn and their colleagues want to use. Their research focuses on developing the method.
Indispensable copper
Accelerators boost the energy of particle beams, and vacuum electronic devices are used in amplifiers and generators. Both rely on components that can be easily shaped and conduct heat and electricity extremely well. Copper has all of these qualities and is therefore widely used.
Traditionally, each copper component is machined individually and bonded with others using heat to form complex geometries. This manufacturing technique is incredibly common, but it has its disadvantages.
“Brazing together multiple parts and components takes a great deal of time, precision and care,” Horn said. “And any time you have a joint between two materials, you add a potential failure point. So, there is a need to reduce or eliminate those assembly processes.”
Potential of 3D copper printing
3D printing of copper components could offer a solution.
It works by layering thin sheets of materials on top of one another and slowly building up specific shapes and objects. In Gamzina’s and Horn’s work, the material used is extremely pure copper powder.
The process starts with a 3D design, or “construction manual,” for the object. Controlled by a computer, the printer spreads a few-micron-thick layer of copper powder on a platform. It then moves the platform about 50 microns – half the thickness of a human hair – and spreads a second copper layer on top of the first, heats it with an electron beam to about 2,000 degrees Fahrenheit and welds it with the first layer. This process repeats over and over until the entire object has been built.
3D printing of a layer of a device known as a traveling wave tube using copper powder. (Christopher Ledford/North Carolina State University)
The amazing part: no specific tooling, fixtures or molds are needed for the procedure. As a result, 3D printing eliminates design constraints inherent in traditional fabrication processes and allows the construction of objects that are uniquely complex.
“The shape doesn’t really matter for 3D printing,” said SLAC staff scientist Chris Nantista, who designs and tests 3D-printed samples for Gamzina and Horn. “You just program it in, start your system and it can build up almost anything you want. It opens up a new space of potential shapes.”
The team took advantage of that, for example, when building part of a klystron – a specialized vacuum tube that amplifies radiofrequency signals – with internal cooling channels at NCSU. Building it in one piece improved the device’s heat transfer and performance.
Compared to traditional manufacturing, 3D printing is also less time consuming and could translate into cost savings of up to 70%, Gamzina said.
A challenging technique
But printing copper devices has its own challenges, as Horn, who began developing the technique with collaborators at RadiaBeam years ago, knows. One issue is finding the right balance between the thermal and electrical properties and strengths of the printed objects. The biggest hurdle for manufacturing accelerators and vacuum electronics, though, is that these high-vacuum devices require extremely high quality and pure materials to avoid part failures, such as cracking or vacuum leaks.
The research team tackled these challenges by first improving the material’s surface quality, using finer copper powder and varying the way they fused layers together. However, using finer copper powder led to the next challenge. It allowed more oxygen to attach to the copper powder, increasing the oxide in each layer and making the printed objects less pure.
So, Gamzina and Horn had to find a way to reduce the oxygen content in their copper powders. The method they came up with, which they recently reported in Applied Sciences, relies on hydrogen gas to bind oxygen into water vapor and drive it out of the powder.
Using this method is somewhat surprising, Horn said. In a traditionally manufactured copper object, the formation of water vapor would create high-pressure steam bubbles inside the material, the material would blister and fail. In the additive process, on the other hand, the water vapor escapes layer by layer, which releases the water vapor more effectively.
Although the technique has shown great promise, the scientists still have a ways to go to reduce the oxygen content enough to print an actual particle accelerator. But they have already succeeded in printing a few components, such as the klystron output cavity with internal cooling channels and a string of coupled cavities that could be used for particle acceleration.
Planning to team up with industry partners
The next phase of the project will be driven by the newly-formed Consortium on the Properties of Additive-Manufactured Copper, which is led by Horn. The consortium currently has four active industry members – Siemens, GE Additive, RadiaBeam and Calabazas Creek Research, Inc – with more on the way.
“This is a nice example of collaboration between an academic institution, a national lab and small and large businesses,” Gamzina said. “It would allow us to figure out this problem together. Our work has already allowed us to go from ‘just imagine, this is crazy’ to ‘we can do it’ in less than two years.”
This work was primarily funded by the Naval Sea Systems Command, as a Small Business Technology Transfer Program with Radiabeam, SLAC, and NCSU. Other SLAC contributors include Chris Pearson, Andy Nguyen, Arianna Gleason, Apurva Mehta, Kevin Stone, Chris Tassone and Johanna Weker. Additional contributions came from Christopher Ledford and Christopher Rock at NCSU and Pedro Frigola, Paul Carriere, Alexander Laurich, James Penney and Matt Heintz at RadiaBeam.
Citation: C. Ledford et al., Applied Sciences, 24 September 2019 (10.3390/app9193993)
SLAC is a vibrant multiprogram laboratory that explores how the universe works at the biggest, smallest and fastest scales and invents powerful tools used by scientists around the globe. With research spanning particle physics, astrophysics and cosmology, materials, chemistry, bio- and energy sciences and scientific computing, we help solve real-world problems and advance the interests of the nation.
SLAC is operated by Stanford University for the U.S. Department of Energy’s Office of Science. The Office of Science is the single largest supporter of basic research in the physical sciences in the United States and is working to address some of the most pressing challenges of our time. For more information, visit energy.gov/science.
Top figure: Examples of 3D-printed copper components that could be used in a particle accelerator: X-band klystron output cavity with micro-cooling channels (at left) and a set of coupled accelerator cavities. (Christopher Ledford/North Carolina State University)
This is a reposting of my news feature, courtesy of SLAC Linear Accelerator Center.
Are the buildings that we live and work in stressing us out?
The answer is probably yes, according to Stanford engineer Sarah Billington, PhD, and her colleagues. They also believe this stress is taking a significant toll on our mental and physical health because Americans typically spend almost 90% of their lives indoors.
During a recent talk at a Stanford Reunion Homecoming alumni celebration, Billington described a typical noisy office cut off from nature and filled with artificial light and artificial materials. This built environment makes workers feel stress, anxiety and distraction, which reduces their productivity and their ability to collaborate with others, she explained.
Now, Billington’s multidisciplinary research team is working to design buildings that instead reduce stress and increase a sense of belonging, physical activity and creativity.
Their first step is to measure how building features — such as airflow, lighting and views of nature — affect human well-being. They are quantifying well-being by measuring levels of stress, belonging, creativity, physical activity and environmental behavior.
In a preliminary online study, the team showed about 300 participants pictures of different office environments and asked them to envision working there at a new job. Across the board, the fictitious work environment was viewed as important to well-being.
“In eight out of the nine things that we were looking at, there were statistically significant increases in their sense of belonging, their self-efficacy and their environmental efficacy when they believed they were going to be working in an environment that had natural materials, natural light or diverse representations,” said Billington.
The researchers are now expanding this work by performing larger lab studies and designing future field studies. They plan to collect data from “smart buildings,” which use high-tech sensors to control the heating, air conditioning, ventilation, lighting, security and other systems. The team also plans to collect data from personal devices such as smartwatches, smartphones and laptops.
By analyzing all of this data, they plan to infer the participants’ behaviors, emotions and physiological states. For example, the researchers will use the building’s occupancy sensors to detect if a worker is interacting with other people who are nearby. Or they will figure out someone’s stress level based on how he or she uses a laptop trackpad and mouse, Billington said.
Stanford computer scientist Pablo Paredes, PhD, who collaborates on the project, explained in a paper how their simple model of arm-hand dynamics can detect stress from mouse motion. Basically, your muscles get tense and stiff when you’re stressed, which changes how you move a computer mouse.
Next, the team plans to use statistical modeling and machine learning to connect these human states to specific building features. They believe this will allow them to design better buildings that improve the occupants’ health.
The researchers said they intend to bring nature indoors by engineering living walls with adaptable acoustic and thermal properties.
They also plan to incorporate dynamic digital displays — such as a large art display on the wall or a small one on an individual’s personal devices — that reflect occupant activity and well-being. For example, a digital image of a flower might represent the energy level of a working group based on how open the petals are, and this could nudge their behavior, Billington said in the talk.
“Our idea is, what if we could make our buildings shape us in a positive way and keep improving over time?” Billington said.
Scientists Talk Funny 
