Published by
Stanford Medicine

Category

Technology

Genetics, NIH, Research, Science, Stanford News, Technology

Of mice and men: Stanford researchers compare mammals' genomes to aid human clinical research

Of mice and men: Stanford researchers compare mammals' genomes to aid human clinical research

Scientists have long considered the laboratory mouse one of the best stand-ins for researching human disease because of the animals’ genetic similarity to humans. Now Stanford researchers, as part of a consortium of more than 30 institutions, have confirmed the mouse’s utility in clinical research by showing that the basic principles controlling genes are similar between the two species. However, they also found some important differences.

From our press release on the work:

“At the end of the day, a lot of the genes are identical between a mouse and a human, but we would argue how they’re regulated is quite different,” said Michael Snyder, PhD, professor and chair of genetics at Stanford. “We are interested in what makes a mouse a mouse and a human a human.”

The research effort, Mouse ENCODE, complements a project called the Encyclopedia of DNA Elements, or ENCODE, both funded by the National Human Genome Research Institute. ENCODE studied specific components in the human genome that guide genes to code for proteins that carry out a cell’s function, a process known as gene expression. Surrounding the protein-coding genes are noncoding regulatory elements, molecules that regulate gene expression by attaching proteins, called transcription factors, to specific regions of DNA.

The Mouse ENCODE consortium annotated the regulatory elements of the mouse genome to make comparisons between the two species. Because many clinical studies and drug discovery use mice as model organisms, understanding the similarities and differences in gene regulation can help researchers understand whether their mouse study applies to humans.

Continue Reading »

Parenting, Pediatrics, Stanford News, Technology

Using texting to boost preschool reading skills

Using texting to boost preschool reading skills

Stanford researchers find promising results from program that uses text messages, like this one, to support parents in helping their children learn to read.

A new program that sends weekly texts to parents to  remind them to engage in simple activities to boost their preschooler’s literacy skills appears to help children read. The program, called READY4K! and developed at the Stanford School of Education by education professor Susanna Loeb, PhD, and graduate student Benjamin York and tested at preschools at the San Francisco Unified School District, underwent an 8-month pilot conducted in 2013-2014. In a release describing the pilot program, Loeb described the challenges faced by parents:

The barrier to some of these positive parenting practices isn’t knowledge or desire, but it’s the crazy, busy lives… It’s difficult to have the time or focus to make all these choices as parents, and we’re helping parents do what they know they should do and what they want to do.

The program enrolled 440 parents, half of whom got literacy building tips by text and the other half got placebo announcements about the district. Parents who received literacy tips were more likely to engage in literacy activities such as reading to their children, reviewing rhyming words and playing word puzzles. Moreover, the authors note in a report that the preschool-age children scored higher on literacy assessment tests at the end of the pilot program than those whose parents had not gotten weekly texts. In the release, a representative of SFUSD notes:

I believe that all families want to be involved in their child’s learning, but many feel they don’t have the time or perceive that supporting their child’s learning might be labor intensive or something that the teacher is better at. The texting program offered some simple nuggets around literacy strategies and validated that families do want to be involved, if given information that is easy to receive and useful.

The READY4K! program was developed with accessibility and scalability in mind. York and Loeb carefully parsed early childhood literacy standards from the state into text-size bites, with the aim that they would be helpful and not add another layer of stress to the already busy parents’ lives.

SFUSD has expanded the program this year to all preschool and kindergarten parents. Loeb and York have heard from other interested school districts and have also added early math skills into the weekly texts.

Previously: Reading, book sharing less common in immigrant families, Stanford study finds, Researcher shows how preschoolers are, quite literally, little scientists and This is your 4-year-old on cartoons
Photo by L.A. Cicero/Stanford News Service

Global Health, Immunology, Pregnancy, Public Health, Stanford News, Technology

Stanford-developed smart phone blood-testing device wins international award

Stanford-developed smart phone blood-testing device wins international award

When I worked as an epidemiologist, one of my jobs was with a program that prevented perinatal hepatitis B infections. That’s when a woman with a chronic hepatitis B infection passes it on to her baby. Babies are more likely than almost any other group to develop chronic infections that can cause them years of health problems and will most likely cut their lives short.

In the U.S., most states have comprehensive testing programs to detect pregnant women with infections and strict protocols that require delivery hospitals to treat babies born to them with vaccination and antibodies to prevent infection with the virus. But a program like this requires a huge administrative and laboratory investment – and in many poverty-stricken parts of the world, this simply isn’t possible. In fact, in California, the vast majority of cases identified by the prenatal testing program are women who were born outside the United States, including many from Asia.

So when I heard the recent news that a team of four Stanford graduate students had won the Nokia Sensing XCHALLENGE, an international competition to for diagnostic devices, for a mobile test that could detect hepatitis B infections, I was pretty impressed and curious about how it could be implemented in those places. The competition is run by XPrize, the same group that has run several competitions for space exploration, and others for super-fuel efficient vehicles and ocean clean-up efforts.

The mobile version of the winning test was one of five awarded top prizes among 90 entrants. It was developed by engineering PhD candidates Daniel Bechstein, Jung-Rok Lee, Joohong Choi and Adi W. Gani, building on work previously done by Stanford professor of materials science and engineering Shan Wang, PhD, and Stanford immunologist  Paul Utz, MD. The device works because magnetic nanoparticles are grafted onto two biological markers: the hepatitis B virus and the antibody that our bodies make in response to the virus. Current tests for hepatitis B requires a full laboratory facility. A Stanford press release describes the device:

The students used a diagnostic strip that takes a finger prick of blood. The patient’s blood flows into a tiny chamber where it mixes with magnetic nanoparticles to form magnetically tagged biomarkers.

The test strip is inserted into a small magnetic detector… The smartphone is plugged into the detector, and its microprocessor helps to perform the test. It takes only a few minutes.

If the test finds the hepatitis B antigen in the blood, the patient is infected and needs treatment. For a newborn with an infected mother, the child needs both vaccination and antibody therapy.

Continue Reading »

Neuroscience, Research, Sleep, Stanford News, Technology

Cheating jet lag: Stanford researchers develop method to treat sleep disturbances

Cheating jet lag: Stanford researchers develop method to treat sleep disturbances

jets landing in sunset - 560

Last month, I went to a conference back East. It was a short trip, four days, and I was jet lagged the whole time. I spent my mornings gulping down hot coffee to help shake off the sleepy haze; in the evenings, when I should have been making up the lost sleep, I was wired, tossing and turning in bed. I could have tried adjusting to East Coast time in the days before I left by getting to bed a few hours earlier and getting up around 4 AM, but that would have required a level of coordination and planning that I’m unlikely to muster in the days before an out-of-town trip.

So I was curious when I learned that a team of Stanford researchers, led by neurobiologist Jamie Zeitzer, PhD, were working on a technique that helps people shift their sleep cycles by flashing light briefly at their eyes while they sleep. They recently published their findings in the Journal of Biological Rhythms.

Beyond the obvious job of vision, our eyes and brain are constantly processing information about the light around us. Light affects our moods and the daily ebb and flow of our biological clocks. It influences when we are sleepiest and most alert. Our brains do a lot of this work behind the scenes and because it happens unconsciously, we are rarely aware of these circadian rhythms – unless something disturbs them, like flying across several time zones.

Zeitzer and his team recruited volunteers and had them get on a routine sleep-wake cycle, going to bed and waking up at the same time every day for about two weeks. The researchers then had the volunteers come sleep in the lab, where the experimental group was given a series brief flashes of light about two millisconds long – about as long as a camera flash – aimed at their eyes. A control group slept in complete darkness, and the volunteers didn’t know which group they were assigned to. The team then measured whether the subjects’ sleep cycle had been affected by measuring the amount of melatonin in their blood. The brain floods the body with melatonin a couple of hours before bedtime and continues releasing the hormone until about an hour after wake time.

The researchers found that the volunteers who got the light flashes were able to shift the sleep phase of their circadian systems. What was surprising was that the intervention did not noticeably disturb the subjects’ sleep. The volunteers in the experimental group didn’t report any less restful sleep than the controls. “This kind of treatment can help people adjust even before they leave for a trip,” says Zeitzer. “Leaving for Australia, the night before you leave, you can adjust a couple of hours. On the plane, you can adjust a couple more. By the time you arrive, you’re already half-way adjusted.”

Besides jet-lagged travelers, this technique could also help teenagers who have a hard time getting up at the right time (a clinical condition for many that goes beyond adolescent laziness) and shift workers. Current treatments for sleep disturbances include sitting in front of bright lights for sometimes hours at a time, which often means it’s only used in extreme cases.

Continue Reading »

Cancer, Research, Science, Stanford News, Surgery, Technology

New molecular imaging could improve bladder-cancer detection

New molecular imaging could improve bladder-cancer detection

Joseph LiaoThey say a picture is worth a thousand words. For bladder-cancer surgeons, an image can be worth many lives.

That’s because a crucial method for detecting bladder cancer is to produce images that allow surgeons to identify abnormal-looking tissue, a method called cystoscopy. In a study published yesterday in Science Translational Medicine, Stanford researchers developed a new way to image the bladder that they say could detect bladder cancer with more accuracy and sensitivity than the standard methods. As described in our press release:

 The researchers identified a protein known as CD47 as a molecular imaging target to distinguish bladder cancer from benign tissues. In the future, this technique could improve bladder cancer detection, guide more precise cancer surgery and reduce unnecessary biopsies, therefore increasing cancer patients’ quality of life.

Identifying cancerous tumors can be challenging — some bladder cancer treatments cause inflammation, which looks very similar to abnormal, cancerous tissue. The only way to know for sure is to perform a biopsy, which can be stressful for the patient. As co-senior author Joseph Liao, MD, explained:

 Our motivation is to improve optical diagnosis of bladder cancer that can better differentiate cancer from non-cancer, which is exceedingly challenging at times. Molecular imaging offers the possibility of real-time cancer detection at the molecular level during diagnostic cystoscopy and tumor resection.

For their work, the researchers looked for a target that would distinguish cancer cells from benign cells and found it in CD47, a protein on a cell’s surface that cancer cells produce in higher quantities than normal cells. In previous work, co-senior author Irving Weissman, MD, developed a CD47 antibody that binds to the cancer cell’s surface and blocks the signal. They hypothesized it would be a good imaging target. More from our release:

 To test their hypothesis, the researchers added a fluorescent molecule to an antibody that binds to CD47. The modified antibodies were then introduced into intact bladders, which had been surgically removed from patients with invasive bladder cancer. Because they bladders were kept in good condition, the study’s imaging methods mirrored the way an urologist might use with a real patient.

After 30 minutes, they rinsed the bladder, so only the antibodies that bound to the CD47 protein remained. When they shine the tumor was exposed to with fluorescent light, the cancer cells “lit up” whereas normal or inflamed cells did not.

“Our goal through better imaging is to deliver a higher- quality cancer surgery and better cancer outcomes,” Liao told me. “I am very excited about the potential to translate our findings to the clinics in the near future.”

Previously: Healing hands: My experience being treated for bladder cancer, Drug may prevent bladder cancer progression, say Stanford researchers, Cellular culprit identified for invasive bladder cancer, according to Stanford study and Mathematical technique used to identify bladder cancer marker
Photo of Liao by Norbert von der Groeben

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

Stanford Medicine Resources: