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Applied Biotechnology, Research, Stanford News, Technology

Tiny size, big impact: Ultrasound powers miniature medical implant

Tiny size, big impact: Ultrasound powers miniature medical implant

14395-chip_newsFor years, scientists have been trying to create implantable electronic devices, but challenges related to powering such technologies has limited their success. Enter a prototype developed by Stanford engineer Amin Arbabian, PhD, and colleagues that uses ultrasound waves to operate the device and send commands.

As explained in a Stanford Report story, researchers designed the “smart chip” to use piezoelectricity, or electricity generated by pressure, as a source of power and selected ultrasound because it has been extensively, and safely, used in medical settings:

[The researchers’] approach involves beaming ultrasound at a tiny device inside the body designed to do three things: convert the incoming sound waves into electricity; process and execute medical commands; and report the completed activity via a tiny built-in radio antenna.

“We think this will enable researchers to develop a new generation of tiny implants designed for a wide array of medical applications,” said Amin Arbabian, an assistant professor of electrical engineering at Stanford.

Every time a piezoelectric structure is compressed and decompressed a small electrical charge is created. The Stanford team created pressure by aiming ultrasound waves at a tiny piece of piezoelectric material mounted on the device.

“The implant is like an electrical spring that compresses and decompresses a million times a second, providing electrical charge to the chip,” said Marcus Weber, who worked on the team with fellow graduate students Jayant Charthad and Ting Chia Chang.

The prototype is about the size of a ballpoint pen head, but the team ultimately wants to make it one-tenth that size. Arbabian and his colleagues are now working with other Stanford collaborators to shrink the device even further, specifically to develop networks of small implantable electrodes for studying brains of laboratory animals.

Previously: Miniature wireless device aids pain studies, Stanford researchers demonstrate feasibility of ultra-small, wirelessly powered cardiac device and Stanford-developed retinal prosthesis uses near-infrared light to transmit images
Photo by Arbabian Lab/Stanford School of Engineering

Cancer, Neuroscience, Stanford News, Technology, Videos

Stanford celebrates 20th anniversary of the CyberKnife

Stanford celebrates 20th anniversary of the CyberKnife

Just about 30 years ago, Stanford neurosurgeon John Adler, MD, traveled to the Karolinksa Institute in Sweden, home to Lars Leksell, MD, and a device Leksell had invented called the Gamma Knife. Leksell had long been a visionary figure in neurosurgery, and Adler – inspired by the device that enables non-invasive brain surgery - began to imagine a next step, driven by the addition of computer technology.

Coming up with an idea, of course, can happen in a matter of minutes. Adler had no idea that it would take 18 years before his next step, the CyberKnife, would treat its first patient. Stanford Hospital was the first to own a CyberKnife, and Adler unhesitatingly admits that without the agreement of hospital administrators to purchase that very first device – designed to treat tumors, brain and spine conditions, as well as cancers of the pancreas, prostate, liver and lungs - its development would not have been completed.

This year, Adler and his Stanford colleagues are celebrating the 20th anniversary of the CyberKnife. Stanford has two, one of just a handful of medical centers with that distinction, and it has accumulated the longest and largest history of patient care with the device. To honor Adler and those Stanford physicians who continue to explore its ever-lengthening list of applications to patient care, a new video featuring Adler was created. It’s a quick glimpse of the determination – and luck – required to make that leap from inspired idea to groundbreaking therapy.

Previously: CyberKnife: From promising technique to proven tumor treatment

Big data, Research, Science, Stanford News, Technology

Gamers: The new face of scientific research?

Gamers: The new face of scientific research?

gamerMuch has been written about the lack of reproducibility of results claimed by even well-meaning, upright scientists. Notably, a 2005 PLoS paper (by Stanford health-research policy expert John Ioannidis, MD, DSci) with the unforgettable title, “Why Most Published Research Findings Are False”, has been viewed more than a million times.

Who knew that relief could come in the form of hordes of science-naive gamers?

The notion of crowdsourcing difficult scientific problems is no longer breaking news. A few years ago I wrote a story about Stanford biochemist Rhiju Das, PhD, who was using an interactive online videogame called EteRNA he’d co-invented to come up with potential structures for RNA molecules.

RNA is a wiggly wonder. Chemically similar to DNA but infinitely more flexible and mobile, RNA can and does perform all kinds of critical tasks within every living cell. Scientists are discovering more about RNA’s once-undreamed of versatility on a steady basis. RNA may even have been around before DNA was, making it the precursor that gave rise to all life on our planet.

But EteRNA gamers need know nothing about RNA, or even about biology. They just need to be puzzle-solvers willing to learn and follow the rules of the game. Competing players’ suggested structures for a given variety of RNA molecule are actually tested in Das’s laboratory to see whether they, indeed, stably fold into the predicted structures.

More than 150,000 gamers have registered on EteRNA; at any given moment, there are about 40 active players plugging away at a solution. Several broadly similar games devoted to pursuing biological insights through crowdsourcing  are also up and running.

Das and EteRNA’s co-inventor, Adrien Treuille, PhD, (now at Carnegie Mellon University) think the gaming approach to biology offers some distinct – and to many scientists, perhaps unexpected – advantages over the more-traditional scientific method by which scientists solve problems: form a hypothesis, rigorously test it in your lab under controlled conditions, and keep it all to yourself until you at last submit your methods, data and conclusions to a journal for peer review and, if all goes well, publication.

In this “think piece” article in Trends in Biochemical Sciences,  Treuille and Das write:

Despite an elaborate peer review system, issues such as data manipulation, lack of reproducibility, lack of predictive tests, and cherry-picking among numerous unreported data occur frequently and, in some fields, may be pervasive.

There is an inherent hint of bias, the authors note, in the notion of fitting one’s data to a hypothesis: It’s always tempting to report or emphasize only data that fits your hypothesis or, conversely, look at the data you’ve produced and then tailor the “hypothesis” accordingly (thereby presenting a “proof” that may never be independently and rigorously tested experimentally).

Das and Treuille argue that the “open laboratory” nature of online games prevents data manipulation, allows rapid tests of reproducibility, and “requires rigorous adherence to the scientific method: a nontrivial prediction or hypothesis must precede each experiment.”

Das says, “It only recently hit us that EteRNA, despite being a game, is an unusually rigorous way to do science.”

Previously: John Ioaniddis discusses the popularity of his paper examining the reliability of scientific researchHow a community of online gamers is changing basic biomedical researchParamecia PacMan: Researchers create video games using living organisms and Mob science: Video game, EteRNA, lets amateurs advance RNA research
Photo by Radly J Phoenix

Mental Health, Research, Technology

How social media can affect your mood

How social media can affect your mood

Facebook_10314A close friend engages in a yearly media detox, where for a period of time he limits his time and activity spent on the Internet. He only answers e-mails requiring an immediate response, spends few minutes reading current news and avoids engaging in social media, shopping online or perusing gossip and entertainment sites. Another friend goes on annual eight-day meditation retreats and turns off her phone for her entire stay. Both report that these periodic breaks significantly improve their moods.

Past research supports their personal experience and shows that while many of use social media to feel connected to others, it can also leave us feeling frustrated, lonely and depressed.

A study (subscription required) recently published online in the journal Computers in Human Behavior offers context to these earlier findings and suggests that when we are feeling blue we use social media sites, such as Facebook, to find friends that are also having a bad day, suffered a setback or going through a tough time in their lives.

During the experiment, researchers gave participants a facial emotion recognition test and randomly told them their performance was “terrible” or “excellent” to put them in positive or negative moods. The individuals were than asked to review profiles on a new social networking site. The profiles used dollar sign or heart icons to make users appear successful and attractive or unattractive and unsuccessful. All profile photos were blurred and the status updates were relatively mundane and similar in tone. PsychCentral reports:

Overall, the researchers found that people tended to spend more time on the profiles of people who were rated as successful and attractive.

But participants who had been put in a negative mood spent significantly more time than others browsing the profiles of people who had been rated as unsuccessful and unattractive.

“If you need a self-esteem boost, you’re going to look at people worse off than you,” [Silvia Knobloch-Westerwick, PhD, co-author of the study] said.

“You’re probably not going to be looking at the people who just got a great new job or just got married.

“One of the great appeals of social network sites is that they allow people to manage their moods by choosing who they want to compare themselves to.”

Previously: Ask Stanford Med: Answers to your questions on the psychological effects of Internet use and Elderly adults turn to social media to stay connected, stave off loneliness
Photo by Paul Walsh

Mental Health, Neuroscience, Technology

What email does to your brain

What email does to your brain

man yellingUpdated 10-2-14: A follow-up post, with tips on how to manage your inbox, can be found here.

***

10-1-14: Have you ever been in a situation in which you were feeling great until you received an email out of the blue that completely upset your day? How does it feel to receive 30 such emails first thing in the morning? There’s a reason why: Research shows that just looking through your inbox can significantly increase your stress levels (see research described here).

Why is this? Let’s start by defining stress. Stress is the experience of having too great a task to accomplish with too few resources to meet the demand. In the past, for our ancestors, this stress might have looked like meeting a hungry wild animal in the jungle. Today, however, it takes on a much more simple, yet equally powerful form: an inbox. Email overload is just another way in which we experience that there is too great a task (the huge list of to-dos) to handle. In the study mentioned above, email overload had a lot to do with the stress response as measured psychologically and physiologically through heart rate, blood pressure and a measure of cortisol (the “stress hormone”).

Is it just the amount of emails that lead to stress though? There’s another element that we are forgetting. The emotional impact of each email. Think about it: Usually, in our email-less past, we would experience maybe one highly emotional event a day or maybe two or three at the most, e.g. a confrontation with a colleague, perhaps a spat with a spouse, and/or a phone call from an angry neighbor. Our stress response is evolved to handle and recover from a small number of stressful situations but not a whole host of them. Unless we live in unusually extreme situations such as warzones, for example, our life usually doesn’t have frequent and sequential stressors thrown at us.

Today, however, just sitting down at our desk to check our email with a cup of coffee can bring on a deluge of emotional assailants. Between 30-300 different emotional stimuli are delivered to you within the span of minutes. From an email from your boss asking you to complete a task urgently, to a passive-aggressive message from a family-member, to news from a colleague that he’s out sick and you have to take over his workload. One hour of email can take you through a huge range of emotions and stressors. Sure, you can get happy emails too – photos of your nephews, someone’s marriage announcement – but unfortunately, research on the negativity bias shows that our brain clings more to the negative and they don’t always balance out.

That’s when our emotional intelligence is impacted. We know that when our stress response is activated, the parts of our brain that respond with fear of anxiety tend to take over, weakening our ability to make rational choices and to reason logically this study). You may be stressed; what’s more, your own ability to respond appropriately is impacted. We know that our emotions impact the way we act. You’re going to reply with a different tone if you’re upset (even at someone other than your email recipient) than if you’re not.

Have you ever pressed “send” only to regret it moments later? Don’t blame yourself. Research shows that getting depleted because you have too much on your plate reduces your self-control. For example, it can make you take more risks when maybe you should be more cautious (e.g. this study). It’s harder to have a say over our impulses when there’s just too much going on. As in too many emails, with too many different messages leading to increased stress and emotional overload.

When you’re doing a million emails – all about different topics and requesting you for different things, you are, by definition in a situation of overwhelmed multitasking. And multitasking, research shows, leads to lower productivity and makes you lose a lot of time out of our day!

So what’s the answer to the assailment of email on our lives?

Before you contemplate moving to a farm, selling your smartphone on Ebay, raising chickens and goats and cutting technology out of your life forever despite your love of selfies – WAIT, there’s a solution. Think about it – email didn’t exist 10 years ago! That means that there is a way to undo the madness. I’ll share a number of tips in my next post… Stay tuned.

Emma Seppala, PhD, is associate director of Stanford’s Center for Compassion and Altruism Research and Education and a research psychologist at the School of Medicine. She is also a certified yoga, pilates, breath work and meditation instructor. A version of this piece originally appeared on her website.

Photo by bark

Applied Biotechnology, Bioengineering, Events, Medical Education, Stanford News, Technology

Stanford physicians and engineers showcase innovative health-care solutions

Stanford physicians and engineers showcase innovative health-care solutions

scholar-poster

A “breathalyzer” that noninvasively determines if patients have unsafe levels of ammonia in their blood. The discovery of a previously approved drug that also fights the Dengue virus. A smartphone-based eye-imaging system that can be used to diagnose vision problems remotely.

These are a few of the 40-plus inventions and clinical solutions presented at the first annual Spectrum Innovation Research Symposium, held last Friday at the Stanford School of Medicine. The event demonstrated the power of bringing together teams of physicians, bioinformaticists and engineers to apply new technologies and ideas to challenging medical problems. Also showcased were budding physician-scientists supported by the Spectrum KL2 and TL1 clinical research training awards. (In the photo above, Colleen Craig, MD, an endocrinology fellow, describes a novel treatment that she’s developing for gastric-bypass patients who suffer from severely low blood sugar.)

The buzz is that it’s going to be a good year for health-care breakthroughs

Spectrum, the recipient of Stanford’s NIH Clinical and Translational Science Award, annually gives up to $50,000 to investigator teams for year-long projects in the areas of drug discovery, medical technologies, predictives/diagnostics, population health sciences and community engagement. This program also provides these teams with training and mentoring to help them move their ideas rapidly from bench to bedside and into the community.

“These modest pilot awards have been immensely successful in stimulating innovative ideas across the spectrum of translational research,” said Spectrum’s director, Harry Greenberg, MD. “They have lead to new inventions that promote individual’s health, new ways of improving the health of the populations and new efforts to assist our surrounding community on health issues.”

As this year’s grantees were rolling up their poster presentations, next year’s scholars were rolling up their sleeves to finish their 2014-15 Spectrum grant proposals, which are due in a few days.

It’s been a pivotal year in medical technology, with the launch of an unprecedented number of game-changing inventions, such as the Mini-ION, a $900 USB-powered DNA sequencer, and Apple HealthKit, a health-and-fitness dashboard and developer kit. In the coming year, these will provide Stanford scholars with amazing technology platforms from which to launch medical solutions that are better, faster and cheaper.

“We are in the middle of amazing biomedical innovation here in Silicon Valley,” said Atul Butte, MD, PhD, and faculty director of the diagnostics/predictives program. “Spectrum enables us to fund the earliest of early technologies, more risky than even the usual angel investments, but with higher potential impacts. In the end, this gets technologies to patients and families that much sooner.”

Because of this, anticipation among the grant-approval committee members at the symposium was high — the buzz is that it’s going to be a good year for health-care breakthroughs.

Previously: Spectrum awards innovation grants to 23 projects, Stanford awarded more than $45 million to spur translational research in medicine, As part of annual tradition, budding physician-scientists display their work, and New class of physician-scientists showcase research
Photo by Kris Newby

Clinical Trials, Immunology, Pain, Research, Stanford News, Surgery, Technology

Discovery may help predict how many days it will take for individual surgery patients to bounce back

Discovery may help predict how many days it will take for individual surgery patients to bounce back

pandaPost-surgery recovery rates, even from identical procedures, vary widely from patient to patient. Some feel better in a week. Others take a month to get back on their feet. And – until now, anyway – nobody has been able to accurately predict how quickly a given surgical patient will start feeling better. Docs don’t know what to tell the patient, and the patient doesn’t know what to tell loved ones or the boss.

Worldwide, hundreds of millions of surgeries are performed every year. Of those, tens of millions are major ones that trigger massive inflammatory reactions in patients’ bodies. As far as your immune system is concerned, there isn’t any difference between a surgical incision and a saber-tooth tiger attack.

In fact, that inflammatory response is a good thing whether the cut came from a surgical scalpel or a tiger’s tooth, because post-wound inflammation is an early component of the healing process. But when that inflammation hangs on for too long, it impedes rather than speeds healing. Timing is everything.

In a study just published in Science Translational Medicine, Stanford researchers under the direction of perioperative specialist Martin Angst, MD, and immunology techno-wizard Garry Nolan, PhD, have identified an “immune signature” common to all 32 patients they monitored before and after those patients had hip-replacement surgery. This may permit reasonable predictions of individual patients’ recovery rates.

In my news release on this study, I wrote:

The Stanford team observed what Angst called “a very well-orchestrated, cell-type- and time-specific pattern of immune response to surgery.” The pattern consisted of a sequence of coordinated rises and falls in numbers of diverse immune-cell types, along with various changes in activity within each cell type.

While this post-surgical signature showed up in every single patient, the magnitude of the various increases and decreases in cell numbers and activity varied from one patient to the next. One particular factor – changes, at one hour versus 24 hours post-surgery, in the activation states of key interacting proteins inside a small set of “first-responder” immune cells – accounted for 40-60 percent of the variation in the timing of these patients’ recovery.

That robust correlation dwarfs those observed in earlier studies of the immune-system/recovery connection – probably because such previous studies have tended to look at, for example, levels of one or another substance or cell type in a blood sample. The new method lets scientists simultaneously score dozens of identifying surface features and goings-on inside cells, one cell at a time.

The Stanford group is now hoping to identify a pre-operation immune signature that predicts the rate of recovery, according to Brice Gaudilierre, MD, PhD, the study’s lead author. That would let physicians and patients know who’d benefit from boosting their immune strength beforehand (there do appear to be some ways to do that), or from pre-surgery interventions such as physical therapy.

This discovery isn’t going to remain relevant only to planned operations. A better understanding, at the cellular and molecular level, of how immune response drives recovery from wounds may also help emergency clinicians tweak a victim’s immune system after an accident or a saber-tooth tiger attack.

Previously: Targeting stimulation of specific brain cells boosts stroke recovery in mice, A closer look at Stanford study on women and pain and New device identifies immune cells at an unprecedented level of detail, inside and out
Photo by yoppy

Applied Biotechnology, Immunology, Infectious Disease, Research, Technology

Artificial spleen shown to filter dangerous pathogens from blood

Artificial spleen shown to filter dangerous pathogens from blood

79118_webOur spleens filter out toxins from our blood and help us fight infections. But serious infections can overpower our bodies’ ability to fight them off, especially among older adults whose immune systems are weaker. Now, a research team led by Donald Ingber, MD, PhD, of Harvard has come up with an artificial “biospleen” that can trap bacteria, fungi and viruses and remove them from circulating blood. Science Magazine describes the device in a news story:

The team first needed a way to capture nasties. They coated tiny magnetic beads with fragments of a protein called mannose-binding lectin (MBL). In our bodies, MBL helps fight pathogens by latching onto them. Ingber and colleagues showed that the sticky beads could grab a variety of microbes in the test tube.

With that key challenge out of the way, the researchers were ready to design the rest of the system. They engineered a microchiplike device a little bigger than a deck of cards that works somewhat like a dialysis machine. As blood enters the device, it receives a dose of the magnetic beads, which snatch up bacteria, and then fans out into 16 channels. As the blood flows across the device, a magnet pulls the beads—and any microbes or toxins stuck to them—out of the blood, depositing them in nearby channels containing saline.

The researchers first tested their device with donated human blood tainted with bacteria. They found that filtering the blood through the device five times could eliminate 90% of the microbes.

The device improved survival rates in rats and may decrease the incidence of sepsis, a dangerous side effect of severe infections. The researchers also found that the device could filter the total volume of blood in an adult human – about 5 liters or (1.3 gallons) – in about five hours.

Previously: Our aging immune systems are still in business, but increasingly thrown out of balance
Image, of the magnetic MBL-coated nanobeads beads capturing pathogens, from Harvard University Wyss Institute

Patient Care, Research, Technology

How can health-care providers better leverage social media to improve patient care?

How can health-care providers better leverage social media to improve patient care?

A growing number of Americans are turning to the Internet for health information and many are using social media tools to engage with patients like themselves or health-care providers. But findings recently published in the Journal of Medical Internet Research suggests that a significant portion of the health-related content on social networking sites is irrelevant or devoted to marketing or promotion of products, events and institutions. Study authors also warned that social media can quickly spread misinformation to a broad audience.

In the study, Stanford medical student Akhilesh Pathipati and colleagues analyzed Facebook search results for common medical conditions. Pathipati explains in a Sacramento Bee opinion piece how health-care providers can adopt social media strategies to address the  concerns mentioned above. He writes:

Providers should build online support systems that reach all patients. A PricewaterhouseCoopers poll found that 40 percent of respondents would use social media to cope with chronic medical conditions. If patients are embarrassed by having a stigmatized illness though, they may lack that coping mechanism.

In the short term, providers may want to set up private groups on social networking sites in which patients can interact with other affected individuals. Setting up an anonymous network may prove to be even more useful, as anonymity has been shown to help people share more about their health. The long-term goal should be to find ways to reduce the stigma associated with certain illnesses.

Previously: Lack of adoption of social media among health-policy researchers = missed opportunity, More reasons for doctors and researchers to take the social-media plunge and A reminder to young physicians that when it comes to social media, “it’s no longer about you”

Bioengineering, Research, Stanford News, Technology

Proteins from pond scum revolutionize neuroscience

Proteins from pond scum revolutionize neuroscience

pond scum smallI wrote a story recently about a cool technique called optogenetics, developed by bioengineering professor Karl Deisseroth, MD, PhD. He won the Keio Prize in Medicine, and I thought it might be interesting to talk with some other neuroscientists at Stanford to get their take on the importance of the technology. You know something is truly groundbreaking when each and every person you interview uses the word “revolutionary” to describe it.

Optogenetics is a technique that allows scientists to use light to turn particular nerves on or off. In the process, they’re learning new things about how the brain works and about diseases and mental health conditions like Parkinson’s disease, addiction and depression.

In describing the award, the Keio Prize committee wrote:

By making optogenetics a reality and leading this new field, Dr. Deisseroth has made enormous contributions towards the fundamental understanding of brain functions in health and disease.

One of the things I found most interesting when writing the story came from a piece Deisseroth wrote several years ago in Scientific American in which he stressed the importance of basic research. Optogenetics would not have been a reality without discoveries made in the lowly algae that makes up pond scum.

“The more directed and targeted research becomes, the more likely we are to slow our progress, and the more certain it is that the distant and untraveled realms, where truly disruptive ideas can arise, will be utterly cut off from our common scientific journey,” Deisseroth wrote.

Deisseroth told me that we need to be funding basic, curiosity-driven research along with efforts to make those discoveries relevant. He said that kind of translation is part of the value of  programs like Stanford Bio-X – an interdisciplinary institute founded in 1998 – which puts diverse faculty members side by side to enable that translation from basic science to medical discovery.

Previously: They said “Yes”: The attitude that defines Stanford Bio-X, New York Times profiles Stanford’s Karl Deisseroth and his work in optogenetics, An in-depth look at the career of Stanford’s Karl Deisseroth, “a major name in science”, Lightning strikes twice: Optogenetics pioneer Karl Deisseroth’s newest technique renders tissues transparent, yet structurally intact, The “rock star” work of Stanford’s Karl Deisseroth and Nature Methods names optogenetics its “Method of the Year
Photo by Tim Elliott, Shutterstock photos

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